The HGNC (HUGO Gene Nomenclature Committee) provides an approved gene name and symbol (short-form abbreviation) for each known human gene. All approved symbols are stored in the HGNC database, and each symbol is unique. In addition, HGNC also provides a unique numerical ID to identify gene families, providing a display of curated hierarchical relationships between families. CC0-1.0 HGNC Gene Group PyOBO v0.12.13-dev-207b46e9 on 2025-10-30T21:07:33.809105 by https://github.com/biopragmatics/pyobo/blob/main/src/pyobo/sources/hgnc/hgncgenefamily.py 2025-10-07 https://www.genenames.org https://www.genenames.org/img/hgnc/logo/hgnc-logo-dark-bckgrnd-large.svg abbreviation exact match in taxon enables gene group VNN Vanin pantetheinases Vanins biotinidase superfamily Vanin family VNN Ubiquitin-activating enzymes, also known as E1 enzymes, catalyze the first step in the ubiquitination reaction, which (among other things) can target a protein for degradation via a proteasome. This covalent attachment of ubiquitin or ubiquitin-like proteins to targeted proteins is a major mechanism for regulating protein function in eukaryotic organisms. E1 enzymes UBA Ubiquitin-like activating enzymes Ubiquitin like modifier activating enzymes UBA CYP1 Cytochrome P450 family 1 CYP1 CYP2 Cytochrome P450 family 2 CYP2 CYP3 Cytochrome P450 family 3 CYP3 CYP4 Cytochrome P450 family 4 CYP4 CYP5 Cytochrome P450 family 5 CYP5 CYP7 Cytochrome P450 family 7 CYP7 CYP8 Cytochrome P450 family 8 CYP8 CYP11 Cytochrome P450 family 11 CYP11 CYP17 Cytochrome P450 family 17 CYP17 CYP19 Cytochrome P450 family 19 CYP19 CYP20 Cytochrome P450 family 20 CYP20 CYP21 Cytochrome P450 family 21 CYP21 CYP24 Cytochrome P450 family 24 CYP24 CYP26 Cytochrome P450 family 26 CYP26 CYP27 Cytochrome P450 family 27 CYP27 CYP39 Cytochrome P450 family 39 CYP39 CYP46 Cytochrome P450 family 46 CYP46 CYP51 Cytochrome P450 family 51 CYP51 Death effector domain containing Ubiquitin-conjugating enzymes, also known as E2 enzymes and more rarely as ubiquitin-carrier enzymes, perform the second step in the ubiquitination reaction that targets a protein for degradation via the proteasome.The ubiquitination process covalently attaches ubiquitin, a short protein of 76 amino acids, to a lysine residue on the target protein. UBE2 Ubiquitin conjugating enzymes E2 UBE2 DAPK Death associated protein kinases DAPK ATG Autophagy related ATG CCR4-NOT deadenylase complex CNOT CCR4-NOT transcription complex CNOT DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N- glycosidic bond. Glycosylases were first discovered in bacteria, and have since been found in all kingdoms of life. In addition to their role in base excision repair DNA glycosylase enzymes have been implicated in the repression of gene silencing in A. thaliana, N. tabacum and other plants by active demethylation. 5-methylcytosine residues are excised and replaced with unmethylated cytosines allowing access to the chromatin structure of the enzymes and proteins necessary for transcription and subsequent translation. DNA glycosylases MBD Methyl-CpG binding domain containing MBD Mismatch repair contributes to the overall fidelity of DNA replication and is essential for combating the adverse effects of damage to the genome. It involves the correction of mismatched base pairs that have been missed by the proofreading element ( Klenow fragment ) of the DNA polymerase complex. The post-replicative Mismatch Repair System (MMRS) of Escherichia coli involves MutS (Mutator S), MutL and MutH proteins, and acts to correct point mutations or small insertion/deletion loops produced during DNA replication. MutS and MutL are involved in preventing recombination between partially homologous DNA sequences. The assembly of MMRS is initiated by MutS, which recognizes and binds to mispaired nucleotides and allows further action of MutL and MutH to eliminate a portion of newly synthesized DNA strand containing the mispaired base. MutS can also collaborate with methyltransferases in the repair of O(6)-methylguanine damage, which would otherwise pair with thymine during replication to create an O(6)mG:T mismatch. MutS exists as a dimer, where the two monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognises the mismatch specifically and has ADP bound. Non-specific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. Mismatch binding induces ATP uptake and a conformational change in the MutS protein, resulting in a clamp that translocates on DNA. MutS is a modular protein with a complex structure, and is composed of: N-terminal mismatch-recognition domain, which is similar in structure to tRNA endonuclease. Connector domain, which is similar in structure to Holliday junction resolvase ruvC. Core domain, which is composed of two separate subdomains that join together to form a helical bundle; from within the core domain, two helices act as levers that extend towards (but do not touch) the DNA. Clamp domain, which is inserted between the two subdomains of the core domain at the top of the lever helices; the clamp domain has a beta-sheet structure. ATPase domain (connected to the core domain), which has a classical Walker A motif. HTH (helix-turn-helix) domain, which is involved in dimer contacts. Homologues of MutS have been found in many species including eukaryotes (MSH 1, 2, 3, 4, 5, and 6 proteins), archaea and bacteria, and together these proteins have been grouped into the MutS family. Although many of these proteins have similar activities to the E. coli MutS, there is significant diversity of function among the MutS family members. This diversity is even seen within species, where many species encode multiple MutS homologues with distinct functions. Inter-species homologues may have arisen through frequent ancient horizontal gene transfer of MutS (and MutL) from bacteria to archaea and eukaryotes via endosymbiotic ancestors of mitochondria and chloroplasts. . MSH MutS ATPases MutS homologs MSH MLH MutL homologs MLH Cytosolic iron-sulfur assembly components Paf1 complex Paf1/RNA polymerase II complex GGA Golgi associated, gamma adaptin ear containing, ARF binding proteins GGA Cullins are a family of hydrophobic proteins providing a scaffold for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in myriad cellular processes. The human genome contains eight cullin genes CUL1, part of SCF complex CUL2, part of ECS complex ( Elongin C - CUL2 - SOCS-box ) CUL3, part of CUL3-BTB complex CUL4A CUL4B CUL5 CUL7 CUL9, also known as PARC There is also a more distant member called ANAPC2 (or APC2), part of the Anaphase-promoting complex. CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as CUL9, also known as p53 cytoplasmic anchor PARC, and the ANAPC2 subunit of the anaphase-promoting complex/cyclosome; both CUL9 and ANAPC2 have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins. With the exception of ANAPC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Nedd8CUL1-F-box protein) E3 Ub ligase complex in Saccharomyces cerevisiae (Baker's yeast), and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue. CUL Cullins CUL SCYL (SCY1) is a family of pseudokinases found in almost all eukaryotes, involved in trafficking of secretory proteins, nuclear tRNA export, and chromosome biology. SCYL SCY1 like pseudokinases SCYL SMC5-6 protein complex SMC5/6 complex GPAT Glycerol-3-phosphate acyltransferases GPAT The MBOAT (membrane bound O-acyl transferase) family of membrane proteins is a family of various acyltransferase enzymes. All family members contain multiple transmembrane domains and most carry two conserved residues which might be active-site residues, a conserved histidine (His) embedded in a hydrophobic stretch of residues and an asparagine (Asn) or histidine within a more hydrophilic region some 30-50 residues upstream. MBOAT enzymes catalyze the transfer of an acyl group from acyl-coenzyme to one of several different substrates. The family is found from bacteria to eukaryotes, and the active region lies outside the membrane. The family may be grouped into four categories, according to function: MBOAT Membrane bound O-acyltransferase family MBOAT BLOC2S Biogenesis of lysosomal organelles complex 2 BLOC2S BLOC3S Biogenesis of lysosomal organelles complex 3 BLOC3S Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein (N-terminus) or peptide substrates. They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular organelles, in cytoplasm, and as membrane components. Aminopeptidases are used in essential cellular functions. Many, but not all, of these peptidases are zinc metalloenzymes. Aminopeptidases LAMTOR Ragulator complex LAMTOR FCP family FCP/SCP family RNA polymerase C-terminal domain phosphatases CTD family phosphatases 5'-nucleotidase ( EC 3.1.3.5 ) is an enzyme which catalyzes the phosphorylytic cleavage of 5'nucleotides. Although originally found in snake venom, the activity of 5'nucleotidase has been described for bacteria and plant cells, and is widely distributed in vertebrate tissue. In mammalian cells the enzyme is predominantly located in the plasma membrane and its primary role is in the conversion of extracellular nucleotides (e.g. 5'-AMP), which are generally impermeable, to the corresponding nucleoside (e.g. adenosine) which can readily enter most cells. Consequently, the enzyme plays a key role in the metabolism of nucleotides. The enzyme has a wide substrate specificity for nucleotides and has been shown to hydrolyze 5'nucleotides rapidly, ribose-5-phosphate slowly, and other phosphate esters extremely slowly (if at all). NT5 5'-nucleotidases NT5 LPIN Lipins LPIN EYA Eyes absent family EYA transcriptional coactivator and phosphatases EYA HAD Asp-based non-protein phosphatases CCN family CYR61/CTGF/NOV matricellular proteins Cellular communication network factors BORCS BLOC-1 related complex subunits BORCS RecQ helicase is a family of helicase enzymes initially found in Escherichia coli that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H 2 O â†' ADP + P and thus driving the unwinding of paired DNA and translocating in the 3' to 5' direction. These enzymes can also drive the reaction NTP + H 2 O â†' NDP + P to drive the unwinding of either DNA or RNA. RECQL RecQ helicases RecQ like helicases RECQL YIPF YIPF protein family Yip1 domain containing YIPF Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double-helical structure. During DNA replication and transcription, DNA becomes overwound ahead of a replication fork. If left unabated, this tension would eventually stop the ability of the enzymes involved in these processes to continue down the DNA strand. In order to prevent and correct these types of topological problems caused by the double helix, topoisomerases bind to either single-stranded or double-stranded DNA and cut the phosphate backbone of the DNA. This intermediate break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed again. Since the overall chemical composition and connectivity of the DNA do not change, the tangled and untangled DNAs are chemical isomers, differing only in their global topology, thus their name. Topoisomerases are isomerase enzymes that act on the topology of DNA. Bacterial topoisomerase and human topoisomerase proceed via the same mechanism for replication and transcription. DNA topoisomerases TOP Topoisomerases TOP The nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC). The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the cell nucleus and the cytoplasm. Nuclear pores in turn allow the transport of water-soluble molecules across the nuclear envelope. Nucleoporins, a family of around 30 proteins, are the main components of the nuclear pore complex in eukaryotic cells. Nucleoporin 62 is the most abundant member of this family. Nucleoporins are able to transport molecules across the nuclear envelope at a very high rate. A single NPC is able to transport 60,000 protein molecules across the nuclear envelope every minute. NPC components NUP Nuclear pore complex components Nucleoporins NUP IGLON IgLON cell adhesion molecules IGLON 14-3-3 proteins are a family of conserved regulatory molecules that are expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and transmembrane receptors. More than 200 signaling proteins have been reported as 14-3-3 ligands. The name 14-3-3 refers to the particular elution and migration pattern of these proteins on DEAE -cellulose chromatography and starch-gel electrophoresis. The 14-3-3 proteins eluted in the 14th fraction of bovine brain homogenate and were found on positions 3.3 of subsequent electrophoresis by Moore and Perez (1967). Elevated amounts of 14-3-3 proteins are found in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. YWHA tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation proteins 14-3-3 phospho-serine/phospho-threonine binding proteins YWHA A ribosomal protein is any of the proteins that, in conjunction with rRNA, make up the ribosomal subunits involved in the cellular process of translation. A large part of the knowledge about these organic molecules has come from the study of E. coli ribosomes. Most ribosomal proteins have been isolated and specific antibodies have been produced. These, together with electronic microscopy and the use of certain reactives, have allowed for the determination of the topography of the proteins in the ribosome. E.coli, other bacteria and Archaea have a 30S small subunit and a 50S large subunit, whereas humans and yeasts have a 40S small subunit and a 60S large subunit. Equivalent subunits are frequently numbered differently between bacteria, Archaea, yeasts and humans. Ribosomal proteins The exocyst is an octameric protein complex involved in vesicle trafficking, specifically the tethering and spatial targeting of post- Golgi vesicles to the plasma membrane prior to vesicle fusion. It is implicated in a number of cell processes, including exocytosis and also cell migration and growth. EXOC Exocyst complex EXOC TNF receptor associated factors also known as TRAFs are a family of proteins primarily involved in the regulation of inflammation, antiviral responses and apoptosis. Currently, seven TRAF proteins have been characterized in mammals : TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6 and TRAF7. Except for TRAF7, these proteins share a relatively conserved secondary structure, including a namesake C-terminal TRAF domain that mediates interactions with other signaling components such as the transmembrane TNF receptors and CD40. TRAF TNF receptor associated factors TRAF Apoptosis regulator Bcl-2 is a family of evolutionarily related proteins. These proteins govern mitochondrial outer membrane permeabilization (MOMP) and can be either pro- apoptotic ( Bax, BAD, Bak and Bok among others) or anti-apoptotic (including Bcl-2 proper, Bcl-xL, and Bcl-w, among an assortment of others). There are a total of 25 genes in the Bcl-2 family known to date. BCL2 BCL2 family BCL2 ATAC ATAC HAT complex ATAC double-histone-acteyltransferase complex ATAC histone acetyltransferase complex Ada2a containing complex ATAC complex ATAC SAGA coactivator complex SAGA transcription coactivator complex Spt-Ada-Gcn5-acetyltransferase complex SAGA complex Y box binding proteins YB proteins YBX Y-box binding proteins YBX Cohesin is a protein complex that regulates the separation of sister chromatids during cell division, either mitosis or meiosis. Cohesin complex Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. It was discovered by Roger D. Kornberg, winner of the 2006 Nobel Prize in Chemistry. It is also referred to in scientific literature as the vitamin D receptor interacting protein ( DRIP ) coactivator complex and the thyroid hormone receptor-associated proteins ( TRAP ). The mediator complex is required for the successful transcription of nearly all class II gene promoters in yeast. It works in the same manner in mammals. The human Mediator complex has 31+ subunits and is 1.2 MDa in size. Its large surface area provides great potential for proteinâ€'protein interaction, even though its sequences do not contain many predicted functional domains. Mediator has been shown to associate with general transcription factors, as well as RNA polymerase II, and is essential for activator-dependent transcription. It has also been demonstrated that the Mediator complex is involved in activator-independent transcription, implying that it may provide a fundamental control of the formation of the initiation complex. Mediator functions as a coactivator and binds to the C-terminal domain of RNA polymerase II holoenzyme, acting as a bridge between this enzyme and transcription factors. DRIP coactivator complex MED TRAP complex Mediator complex MED Golgi dynamics domain containing GOLD domain containing SEC14 SEC14 family SEC14 TMED TMED/p24 protein family p24 family transmembrane emp24-like trafficking proteins Transmembrane p24 trafficking proteins TMED IGFBP Insulin like growth factor binding proteins IGFBP Lipid phosphatases LPPs Lipid phosphate phosphatases PLPP Type 2 phosphatidic acid phosphatases Phospholipid phosphatases PLPP SGPP SPP phosphatases Sphingosine-1-phosphate phosphatases SGPP Acid phosphatase ( EC 3.1.3.2, acid phosphomonoesterase, phosphomonoesterase, glycerophosphatase, acid monophosphatase, acid phosphohydrolase, acid phosphomonoester hydrolase, uteroferrin, acid nucleoside diphosphate phosphatase, orthophosphoric-monoester phosphohydrolase (acid optimum) ) is a phosphatase, a type of enzyme, used to free attached phosphoryl groups from other molecules during digestion. It can be further classified as a phosphomonoesterase. ACP Acid phosphatase family Acid phosphatases ACP Alkaline phosphatase ( ALP, ALKP, ALPase, Alk Phos ) ( EC 3.1.3.1 ) is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation. As the name suggests, alkaline phosphatases are most effective in an alkaline environment. ALP Alkaline phosphatases ALP Sugar phosphatases Glucose 6-phosphatase ( EC 3.1.3.9, G6Pase) is an enzyme that hydrolyzes glucose-6-phosphate, resulting in the creation of a phosphate group and free glucose. Glucose is then exported from the cell via glucose transporter membrane proteins. This catalysis completes the final step in gluconeogenesis and glycogenolysis and therefore plays a key role in the homeostatic regulation of blood glucose levels. G6Pase is a complex of multiple component proteins, including transporters for G6P, glucose, and phosphate. The main phosphatase function is performed by the G6Pase catalytic subunit. G6PC G6Pases Glucose 6-phosphatases, catalytic G6PC Fructose bisphosphatase ( EC 3.1.3.11 ) is an enzyme that converts fructose-1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis and the Calvin cycle which are both anabolic pathways. Fructose bisphosphatase catalyses the reverse of the reaction which is catalysed by phosphofructokinase in glycolysis. FBP Fructose-1,6-bisphosphatases FBP Phosphatases PFKFB 6-phosphofructo-2-kinases/fructose-2,6-biphosphatases PFKFB Phosphoglycerate mutase (PGM) is an enzyme that catalyzes step 8 of glycolysis. It catalyzes the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG) through a 2,3-bisphosphoglycerate intermediate. These enzymes are categorized into the two distinct classes of either cofactor -dependent (dPGM) or cofactor-independent (iPGM). The dPGM enzyme (EC 5.4.2.11) is composed of approximately 250 amino acids and is found in all vertebrates as well as in some invertebrates, fungi, and bacteria. PGAM Phosphoglycerate mutases PGAM Phosphoinositide phosphatases In enzymology, a bisphosphoglycerate phosphatase ( EC 3.1.3.13 ) is an enzyme that catalyzes the chemical reaction 2,3-bisphospho-D-glycerate + H 2 O 3-phospho-D-glycerate + phosphate Thus, the two substrates of this enzyme are 2,3-bisphospho-D-glycerate and H 2 O, whereas its two products are 3-phospho-D-glycerate and phosphate. Bisphosphoglycerate phosphatases The HAD phosphatase family are named after the bacterial enzyme haloacid dehydrogenase and employ an Asp-based catalytic mechanism. The family includes both protein and non-protein phosphatases. HAD Asp-based phosphatases Golgins MCM MCM ATPases MCM domain containing MCM8-9 complex minichromosome maintenance complex minichromosome maintenance family minichromosome maintenance replicative helicase MCM family MCM The MADS box is a conserved sequence motif found in genes which comprise the MADS-box gene family. The MADS box encodes the DNA-binding MADS domain. The MADS domain binds to DNA sequences of high similarity to the motif CC 6 GG termed the CArG-box. MADS-domain proteins are generally transcription factors. The length of the MADS-box reported by various researchers varies somewhat, but typical lengths are in the range of 168 to 180 base pairs, i.e. the encoded MADS domain has a length of 56 to 60 amino acids. There is evidence that the MADS domain evolved from a sequence stretch of a type II topoisomerase in a common ancestor of all extant eukaryotes. MADS box transcription factors MCM1, AGAMOUS, DEFICIENS, and SRF box transcription factor family MADS box family LEM domain proteins LEMD LEM domain containing LEMD SPIN Spindlin family SPIN ACKR Atypical chemokine receptors ACKR CCR Chemokine (C-C motif) receptors C-C motif chemokine receptors CCR Chemokine (X-C motif) receptors XCR X-C motif chemokine receptors XCR CX3CR Chemokine (C-X-3-C motif) receptors C-X-3-C motif chemokine receptors CX3CR CXCR Chemokine (C-X-C motif) receptors C-X-C motif chemokine receptors CXCR Ephrin receptors (Ephs) are a group of receptors that are activated in response to binding ephrin. Ephs form the largest known subfamily of receptor tyrosine kinases (RTKs). Both Ephs and their corresponding ephrin ligands are membrane-bound proteins that require direct cell-cell interactions for Eph receptor activation. Ephephrin signaling has recently been identified to play a critical role in the maintenance of several processes during adulthood including long-term potentiation, angiogenesis, and stem cell differentiation and cancer. EPH Ephrin receptors EPH receptors EPH The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1 (EGFR, ErbB1 ), Her2 (Neu, ErbB2), Her3 (ErbB3), and Her4 (ErbB4). The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's Disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ERBB ErbB family Erb-b2 receptor tyrosine kinases ERBB Myosin-I isoforms are the single-headed, membrane-associated members of the myosin superfamily found in most eukaryotic cells. They play essential roles in membrane dynamics, cytoskeletal structure, mechanical signal-transduction and endosome processing. MYO1 Myosin heavy chains, class I MYO1 Myosin-II isoforms are the major contractile proteins in muscle and also play several crucial roles in non-muscle contractility. Myosin-II molecules contain two motor domains and assemble into bipolar filaments. MYH Myosins, class II Myosin heavy chains, class II MYH Class III myosins (MYO3) are novel in that they contain an amino-terminal kinase domain connected to the canonical myosin motor domain. MYO3 Myosin heavy chains, class III MYO3 Myosin-V transports vesicles along actin filament tracks over long distances as a single, two-headed molecule. MYO5 Myosin heavy chains, class V MYO5 Due to a unique addition to the lever arm-positioning region (converter), class VI myosins move in the opposite direction (toward the minus-end of actin filaments) compared to other characterized myosin classes. MYO6 Myosin heavy chains, class VI MYO6 The class VII myosins are characterized by the presence of two FERM domains in their C-terminal tail region MYO7 Myosin heavy chains, class VII MYO7 Class IX myosins are single-headed actin motors that have a conserved RhoGAP domain and an insertion in loop2 of the myosin head domain. MYO9 Myosin heavy chains, class IX MYO9 Myosin-X is the founding member of a class of unconventional myosins characterized by a tail domain containing multiple pleckstrin homology domains. MYO10 Myosin heavy chains, class X MYO10 MYO15 Myosin heavy chains, class XV MYO15 MYO16 Myosin heavy chains, class XVI MYO16 MYO18 Myosin heavy chains, class XVIII MYO18 MYO19 Myosin heavy chains, class XIX MYO19 Keratin is a family of fibrous structural proteins. Keratin is the key structural material making up the outer layer of human skin. It is the key structural component of hair and nails, and it provides the necessary strength and toughness for masticatory organs, such as the tongue and the hard palate. Keratin monomers assemble into bundles to form intermediate filaments, which are tough and form strong unmineralized tissues found in reptiles, birds, amphibians, and mammals. The only other biological matter known to approximate the toughness of keratinized tissue is chitin. KRT Keratins KRT SLFN Schlafen family SLFN The endosomal sorting complexes required for transport ( ESCRT ) machinery is made up of cytosolic protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm. These ESCRT components have been isolated and studied in a number of organisms including yeast and humans. The ESCRT machinery plays a vital role in a number of cellular processes including multivesicular body (MVB) biogenesis, cellular abscission, and viral budding. Multivesicular body (MVB) biogenesis is a process in which ubiquitin tagged proteins enter organelles called endosomes via the formation of vesicles. This process is essential for cells to destroy misfolded and damaged proteins. Without ESCRT machinery, these proteins can build up and lead to neurodegenerative disease. For example, abnormalities in ESCRT-III components can lead to neurological disorders such as hereditary spastic paraplegia (HSP). Cellular abscission, the process by which the membrane connecting two daughter cells is cleaved, is also mediated by ESCRT machinery. Without the ESCRT complexes, daughter cells could not separate and abnormal cells containing twice the amount of DNA would be generated. These cells would inevitably be destroyed through a process known as apoptosis. Lastly, viral budding, or the process by which specific types of viruses exit cells, may not occur in the absence of ESCRT machinery. This would inevitably prevent viruses from spreading from cell to cell. endosomal sorting complexes required for transport ESCRT complexes ACTN Actinins ACTN Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. The protein is named spectrin since it was first isolated as a major protein component of human red blood cells which had been treated with mild detergents; the detergents lysed the cells and the hemoglobin and other cytoplasmic components were washed out. In the light microscope the basic shape of the red blood cell could still be seen as the spectrin containing submembranous cytoskeleton preserved the shape of the cell in outline. This became known as a red blood cell 'ghost', and so the major protein of the ghost was named spectrin. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure. The hexagonal arrangements are formed by tetramers of spectrin subunits associating with short actin filaments at either end of the tetramer. These short actin filaments act as junctional complexes allowing the formation of the hexagonal mesh. In certain types of brain injury such as diffuse axonal injury, spectrin is irreversibly cleaved by the proteolytic enzyme calpain, destroying the cytoskeleton. Spectrin cleavage causes the membrane to form blebs and ultimately to be degraded, usually leading to the death of the cell. Spectrin subunits may also be cleaved by caspase family enzymes, and calpain and caspase produce different spectrin breakdown products which can be detected by western blotting with appropriate antibodies. Calpain cleavage may indicate activation of necrosis, while caspase cleavage may indicate apoptosis. SPT Spectrins SPT Flotillins are ubiquitous and highly conserved proteins. They were initially discovered as being associated with specific caveolin-independent cholesterol- and glycosphingolipid-enriched membrane microdomains and as being expressed during axon regeneration. Flotillins have a role in a large number of physiopathological processes, mainly through their function in membrane receptor clustering and in the regulation of clathrin-independent endocytosis. FLOT Flotillins FLOT endosomal sorting complex required for transport 0 ESCRT-0 endosomal sorting complex required for transport I ESCRT-I endosomal sorting complex required for transport II ESCRT-II endosomal sorting complex required for transport III ESCRT-III ESCRT-III associated factors ESCRT-IV EIF3 eIF3 Eukaryotic translation initiation factor 3 EIF3 The BBSome is a component of the basal body and is involved in formation of the primary cilium. The BBSome is a complex of seven Bardet-Biedl syndrome (BBS) proteins: BBS1, BBS2, BBS4, BBS5, BBS7, TTC8 (aka BBS8) and BBS9. In addition the BBSome contains the BBIP10 protein. BBSome SNARE proteins (an acronym derived from ' SNAP (Soluble NSF Attachment Protein) REceptor') are a large protein superfamily. The primary role of SNARE proteins is to mediate vesicle fusion, that is, the fusion of vesicles with their target membrane bound compartments (such as a lysosome). The best studied SNAREs are those that mediate docking of synaptic vesicles with the presynaptic membrane in neurons. soluble N-ethylmaleimide-sensitive factor attachment protein receptors SNAREs Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. :574 In extreme cases, all exposure to sunlight must be forbidden, no matter how small; as such, individuals with the disease are often colloquially referred to as children of the night. Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP; metastatic malignant melanoma and squamous cell carcinoma are the two most common causes of death in XP victims. This disease involves both sexes and all races, with an incidence of 1:250,000 in the United States. XP is roughly six times more common in Japanese people than in other groups. Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high-energy light leads to the formation of pyrimidine dimers, namely cyclobutane-pyrimidine dimers and pyrimidine-6-4-pyrimidone photoproducts. In a healthy, normal human being, the damage is first excised by endonucleases. DNA polymerase then repairs the missing sequence, and ligase 'seals' the transaction. This process is known as nucleotide excision repair. XP Xeroderma pigmentosum complementation groups XP Lipid phosphatase superfamily Phospholipid phosphatase superfamily Lipid phosphatase related PLPPR Plasticity-related genes Phospholipid phosphatase related PLPPR YPEL Yippee like family YPEL GEMIN Gem nuclear organelle associated proteins Gemins GEMIN N-terminal acetyltransferases NAT N-acetyltransferases NAT In enzymology, an arylamine N-acetyltransferase ( EC 2.3.1.5 ) is an enzyme that catalyzes the chemical reaction acetyl-CoA + an arylamine CoA + an N-acetylarylamine Thus, the two substrates of this enzyme are acetyl-CoA and arylamine, whereas its two products are CoA and N-acetylarylamine. This enzyme belongs to the family of transferases, specifically those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is acetyl-CoA:arylamine N-acetyltransferase. Other names in common use include arylamine acetylase, beta-naphthylamine N-acetyltransferase, 4-aminobiphenyl N-acetyltransferase, acetyl CoA-arylamine N-acetyltransferase, 2-naphthylamine N-acetyltransferase, arylamine acetyltransferase, indoleamine N-acetyltransferase, N-acetyltransferase, p-aminosalicylate N-acetyltransferase, serotonin acetyltransferase, and serotonin N-acetyltransferase. Arylamine N-acetyltransferases GNAT GCN5 related N-acetyltransferases TMC Transmembrane channel like family TMC CT antigen 1 family CT antigen 3 family CT antigen 7 family MAGE Melanoma antigen family MAGE family MAGE Stathmin 1/oncoprotein 18, also known as STMN1, is a highly conserved 17 kDa protein. Its function as an important regulatory protein of microtubule dynamics has been well-characterized. Eukaryotic microtubules are one of three major components of the cell's cytoskeleton. They are highly dynamic structures that continuously alternate between assembly and disassembly. Stathmin performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cell's needs. Microtubules are cylindrical polymers of α,β-tubulin. Their assembly is in part determined by the concentration of free tubulin in the cytoplasm. At low concentrations of free tubulin, the growth rate at the microtubule ends is slowed and results in an increased rate of depolymerization (disassembly). STMN Stathmins STMN BAG BCL2 associated athanogene family BAG cochaperones BAG Tropomodulin is a protein which binds and caps the minus end of actin (the 'pointed' end), regulating the length of actin filaments in muscle and non-muscle cells. The protein functions by physically blocking the spontaneous dissociation of ADP -bound actin monomers from the minus end of the actin fibre. This, along with plus end capping proteins, such as capZ stabilise the structure of the actin filament. End capping is particularly important when long-lived actin filaments are necessary, for example: in myofibrils. Inhibition of tropomodulin capping activity leads to dramatic increase in thin filament length from its pointed end. TMOD Tropomodulins TMOD PTX Pentraxins PTX Long pentraxins Short pentraxins Ypt-interacting protein family YIP superfamily AFF AF4/FMR2 family AFF GRAM GRAM domain containing GRAM PWWP PWWP domain containing PWWP NDUF, MT-ND NADH:ubiquinone oxidoreductase core subunits NDUF, MT-ND NDUF NADH:ubiquinone oxidoreductase supernumerary subunits NDUF PITPN Phosphatidylinositol transfer proteins PITPN RFX Regulatory factor X-box binding proteins Regulatory factor X family RFX MAPKAPK Mitogen-activated protein kinase-activated protein kinases MAPK activated protein kinases MAPKAPK This family includes the RAF kinases and the KSR scaffold proteins. All of the genes are related by homology but the KSR genes are 'pseudokinases' and have no kinase function. RAF family LRRC8 Volume regulated anion channel subunits LRRC8 ITGB Integrin beta subunits ITGB ITGA Integrin alpha subunits ITGA The TAS1R1+TAS1R3 heterodimer receptor functions as the savory receptor, responding to L-amino acid binding, especially L-glutamate. The umami taste is most frequently associated with the food additive monosodium glutamate (MSG) and can be enhanced through the binding of inosine monophosphate (IMP) and guanosine monophosphate (GMP) molecules. The TAS1R2+TAS1R3 heterodimer receptor functions as the sweet receptor by binding to a wide variety of sugars and sugar substitutes. TAS1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth. Sweet and umami taste receptors Sweet taste receptors T1R receptors T1Rs TAS1R Taste receptors, type 1 Type 1 taste receptors Taste 1 receptors TAS1R The TAS2R proteins function as bitter taste receptors. There are 43 human TAS2R genes, each of which (excluding the five pseudogenes) lacks introns and codes for a GPCR protein. These proteins, as opposed to TAS1R proteins, have short extracellular domains and are located in circumvallate papillae, palate, foliate papillae, and epiglottis taste buds, with reduced expression in fungiform papillae. Bitter taste receptors T2R receptors T2Rs TAS2R Taste receptors, type 2 Type 2 taste receptors Taste 2 receptors TAS2R LIM PINCH class LIM and senescent cell antigen-like domains containing LIM zinc finger domain containing LIM-type zinc finger domains LIMS Zinc fingers, LIM-type LIMS zinc finger family LIMS BORG CDC42EP CEP binder of Rho GTPases CDC42 effector proteins CDC42EP CEBP CCAAT/enhancer binding proteins CEBP Helicases are a class of enzymes vital to all living organisms. Their main function is to unpackage an organism's genes. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands (i.e., DNA, RNA, or RNA-DNA hybrid) using energy derived from ATP hydrolysis. There are many helicases resulting from the great variety of processes in which strand separation must be catalyzed. Approximately 1% of eukaryotic genes code for helicases. The human genome codes for 95 non-redundant helicases: 64 RNA helicases and 31 DNA helicases. Many cellular processes, such as DNA replication, transcription, translation, recombination, DNA repair, and ribosome biogenesis involve the separation of nucleic acid strands that necessitates the use of helicases. Helicases UPF1 like RNA helicases Skp, Cullin, F-box containing complex (or SCF complex ) is a multi-protein E3 ubiquitin ligase complex catalyzing the ubiquitination of proteins destined for proteasomal degradation. It has important roles in the ubiquitination of proteins involved in the cell cycle and also marks various other cellular proteins for destruction. Core Components SCF contains three core subunits, and a number of less critical components: F-box protein ( e.g. Cdc4 ) â€' Contributes to the specificity of SCF by aggregating to target proteins independently of the complex and then binding to the Skp1 component, thus allowing the protein to be brought into proximity with the functional E2 protein. The F-box is also essential in regulating SCF activity during the course of the cell-cycle. SCF levels are thought to remain constant throughout the cell-cycle. Instead, F-box affinity for protein substrates is regulated through cdk/cyclin mediated phosphorylation of target proteins. Skp1 â€' Skp1 is a bridging protein and forms part of the horseshoe-shaped complex in tandem with cullin (cul1). Skp1 is essential in the recognition and binding of the F-box. Cullin ( CUL1 ) â€' CUL1 forms the major structural scaffold of the SCF complex and links the skp1 domain with the Rbx1 domain. RBX1 â€' Rbx1 contains a small zinc-binding domain called the RING Finger, to which the E2-ubiquitin conjugate binds, allowing the transferral of the ubiquitin to a lysine residue on the target protein. SCF and Cell Cycle Regulation Progression through the cell cycle in eukaryotes is regulated through synthesisdephosphorylation of cell-cycle-regulating proteins. Two ubiquitin ligases are crucial in the cell cycle. The anaphase-promoting complex or cyclosome ( APC/C ) controls the metaphase â€' anaphase transition when bound to its substrate-specific activating subunit Cdc20 : this complex ubiquitinylates the separase -inhibiting protein securin, paving the way for separase to break cohesin and thus separate the sister chromatids at the centromere. APC/C with another activating subunit, Cdh1, is active in G1 phase and controls levels of the mitosis-regulating B-type cyclins. SCF controls the transitions between G1/S and G2/M phases. Two F-box-protein-bound SCF complexes (SCF- Skp2 and SCF- β-TrCP ), are most well studied among over 70 F-box proteins identified in humans. SCF-Skp2 mainly ubiquitinates and degrades cyclin-dependent kinase inhibitors (CKIs) such as p27 and p21 as well as the G1-/S-specific cyclin E, in vivo and in vitro. Therefore, SCF-Skp2 promotes cell-cycle progression and cell growth. On the other hand, SCF-βTrCP promotes proteolysis of Emi1, an APC/C-Cdh1 inhibitor, and Wee1, a Cdk1 inhibitor, in early mitosis via phosphorylation at their degron (the amino acid motif DSGXXS, where X can be any amino acid) by kinases such as Polo-like kinase 1 (Plk1) and Cdk1â€'cyclin B. SCF-βTrCP and APC/C control each other to regulate timely progression through the cell cycle. Lists of substrates of SCF-Skp2 and -βTrCP are still growing. SCF and Plant Hormone Signaling In plants, the plant hormone auxin stimulates binding of SCF-TIR1 to the AUX/IAA repressor and then the degradation of the repressor, resulting in the activation of auxin-responsive genes. The TIR1 F-box protein acts as an auxin receptor and directly links reception of auxin to degradation of the Aux/IAA proteins. TIR1 (Transport Inhibitor Response 1) belongs to AFBs (Auxin Signaling F-box proteins). In plants, the plant hormone Jasmonate allows binding between SCF-COI1 to the JAZ transcription factor. Degradation of the JAZ transcription factor allows for the transcription of the jasmonate responsive genes. SCF complex LY Lysozymes LY Glycoside Hydrolase Family 23 LYG goose-type lysozyme Lysozymes, g-type LYG Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases. These are enzymes ( EC 3.2.1.17 ) that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins. Lysozyme is abundant in a number of secretions, such as tears, saliva, human milk, and mucus. It is also present in cytoplasmic granules of the macrophages and the polymorphonuclear neutrophils (PMNs). Large amounts of lysozyme can be found in egg white. C-type lysozymes are closely related to alpha-lactalbumin in sequence and structure, making them part of the same family. In humans, the lysozyme enzyme is encoded by the LYZ gene. Glycoside Hydrolase Family 22 LYZ chicken-type lysozyme Lysozymes, c-type LYZ prolactin family somatotropin family Growth hormone family Diacylglycerol kinase (DGK or DAGK) is a family of enzymes that catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low allowing DAG to be used for glycerophospholipid biosynthesis but on receptor activation of the phosphoinositide pathway, DGK activity increases driving the conversion of DAG to PA. As both lipids are thought to function as bioactive lipid signaling molecules with distinct cellular targets, DGK therefore occupies an important position, effectively serving as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. In bacteria, DGK is very small (13 to 15 kD) membrane protein which seems to contain three transmembrane domains. The best conserved region is a stretch of 12 residues which are located in a cytoplasmic loop between the second and third transmembrane domains. Some Gram-positive bacteria also encode a soluble diacylglycerol kinase capable of reintroducing DAG into the phospholipid biosynthesis pathway. DAG accumulates in Gram-positive bacteria as a result of the transfer of glycerol-1-phosphate moieties from phosphatidylglycerol to lipotechoic acid. DGK Diacylglycerol kinases DGK Sushi domain is an evolutionary conserved protein domain. Sushi domains, also known as Complement control protein (CCP) modules, or short consensus repeats (SCR), exist in a wide variety of complement and adhesion proteins. The structure is known for this domain; it is based on a beta-sandwich arrangement - one face made up of three beta-strands hydrogen-bonded to form a triple-stranded region at its centre, and the other face formed from two separate beta-strands. Sushi domain containing MYPT Myosin phosphatase targeting family MYPT Activating LILRs (LILRAs) have short cytoplasmic domains lacking signaling motifs but transmit activating signals by linking to immunoreceptor tyrosine-based activation motifs of the FcR gamma-chain. Activating LILRs LILRA leukocyte immunoglobulin like receptor A subfamily Activating leukocyte immunoglobulin like receptors LILRA Inhibitory LILRs (LILRBs) contain cytoplasmic tails with immunoreceptor tyrosine-based inhibitory motifs that provide negative signals. Inhibiting LILRs Inhibitory LILRs LILRB Leukocyte immunoglobulin like receptor B subfamily Inhibitory leukocyte immunoglobulin like receptors LILRB TEAD TEFs transcriptional enhancer factors TEA domain transcription factors TEAD PRICKLE Prickle homologs Prickle planar cell polarity proteins PRICKLE Classical cadherins have an ectodomain comprising at least five consecutive cadherin repeats, a single transmembrane domain and a cytoplasmic domain containing two conserved motifs for binding to catenins. Type I classical cadherins are characterised by the presence of an HAV motif in the first extracellular repeat. CDH Type I classical cadherins CDH Classical cadherins have an ectodomain comprising at least five consecutive cadherin repeats, a single transmembrane domain and a cytoplasmic domain containing two conserved motifs for binding to catenins. Type II classical cadherins differ from type I classical cadherins because they lack an HAV motif in the first extracellular repeat. CDH Type II classical cadherins CDH The striking common features of [7D-cadherins] are the seven extracellular cadherin repeats and the partial lack of the Ca2+-binding motifs at the interface between cadherin repeats 2 and 3. 7D cadherins The desmosomal cadherins, desmogleins (Dsgs) and desmocollins (Dscs), are transmembrane molecules that mediate adhesion through their extracellular domains and serve as a scaffold for assembly of the desmosomal plaque through their cytoplasmic domains. DSC, DSG Desmosomal cadherins DSC, DSG CELSR CELSR cadherins CELSR Snf2-family proteins are so-called owing to the presence of a domain that is homologous to the helicase-like ATPase domain of the Saccharomyces cerevisiae Snf2 protein. This domain, the Snf2 domain, consists of two tandem RecA-like folds and contains seven conserved helicase-related sequence motifs that classify it as part of the Superfamily 2 (SF2) grouping of helicase-like proteins. SNF2 family SNF2, N-terminal domain containing SNF2-like Snf2 helicase-related ATPases Snf2-related helicases SNF2 related family Mannosidase is an enzyme which hydrolyzes mannose. Mannosidases Alpha-mannosidases Mannosidases type alpha Class 1 alpha-mannosidases recognize and cleave only alpha-1,2–linked mannose residues from the Man9GlcNAc2 high-mannose precursor. Class 1 (Family 47 Glycosylhydrolase) alpha 1,2-Mannosidases Class 1 alpha 1,2-mannosidases Class I alpha mannosidases Glycoside Hydrolase Family 47 MAN1 Mannosidases alpha class 1 MAN1 Glycoside hydrolases of family 38 are Class II α-mannosidases. They range in breadth of specificity from the Golgi α-mannosidase (2A1), which has a dual specificity for α-1,6 and α-1,3-linked mannoses, to the lysosomal mannosidases, which have either broad (2B1 cleaves α1,2, α1,3 and α1,6 linkages) or narrow specificities (2B2 is specific for α-1,6). There have been GH38 mannosidases identified in a number of different localizations, classed into subfamilies with different substrate specificities and biochemical properties, and, presumably, different physiological roles. The Golgi enzyme is identified as 2A1 (Class 2, A for Golgi, enzyme 1). Lysosomal GH38 mannosidases are indicated by 'B' (2B1, 2B2) and those likely existing in the cytoplasm by 'C'. Class 2 alpha-mannosidases Class II alpha-mannosidases Glycoside Hydrolase Family 38 MAN2 Mannosidases alpha class 2 MAN2 Endo-alpha mannosidases Glycoside Hydrolase Family 99 MANEA Mannosidases endo-alpha MANEA Beta-mannosidase ( EC 3.2.1.25, mannanase, mannase, beta-D-mannosidase, beta-mannoside mannohydrolase, exo-beta-D-mannanase, lysosomal beta A mannosidase ) is an enzyme with system name beta-D-mannoside mannohydrolase, which is in humans encoded by the MANBA gene. Beta-mannosidases MANBA Mannosidases type beta MANBA Prdm genes encode transcription factors with a subtype of SET domain known as the PRDF1-RIZ (PR) homology domain and a variable number of zinc finger motifs. PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) homologous domain containing PRDM PR/SET domain family PRDM RASSF Ras association domain family RASSF Kainate receptors, or KARs, are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from the red alga Digenea simplex. KARs are less understood than AMPA and NMDA receptors, the other ionotropic glutamate receptors. Postsynaptic kainate receptors are involved in excitatory neurotransmission. Presynaptic kainate receptors have been implicated in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. GRIK Glutamate receptors, ionotropic, kainate KARs Kainate receptors Glutamate ionotropic receptor kainate type subunits GRIK Vesicle associated membrane proteins (VAMP) are a family of SNARE proteins with similar structure, and are mostly involved in vesicle fusion. VAMP Vesicle associated membrane proteins VAMP AMPA receptor subunits AMPA receptors GRIA Glutamate receptors, ionotropic, AMPA Glutamate ionotropic receptor AMPA type subunits GRIA The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel protein found in nerve cells. It is activated when glutamate and glycine (or D-serine ) bind to it, and when activated it allows positively charged ions to flow through the cell membrane. The NMDA receptor is very important for controlling synaptic plasticity and memory function. The NMDAR is a specific type of ionotropic glutamate receptor. The NMDA receptor is named this because the agonist molecule N -methyl-D-aspartate (NMDA) binds selectively to it, and not to other glutamate receptors. GRIN Glutamate receptors, ionotropic, N-methyl D-aspartate N-methyl-D-aspartate receptors NMDA receptors NMDARs Glutamate ionotropic receptor NMDA type subunits GRIN GRID Glutamate receptors, ionotropic, delta Glutamate ionotropic receptor delta type subunits GRID Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming α subunit, which may be associated with either one or two beta subunits. Alpha-subunits consist of four homologous domains (I–IV), each containing six transmembrane segments (S1–S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. Sodium voltage-gated channel alpha subunits Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming alpha subunit, which may be associated with either one or two beta subunits. Auxiliary beta1, beta2, beta3 and beta4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain. Sodium voltage-gated channel beta subunits DPP4 activity and/or structural homolog family DASH family ATP1 Na+/K+-ATPases ATPase Na+/K+ transporting subunits ATP1 ATP2 Ca2+-ATPases PMCAs SERCAs type IIA P-type ATPases type IIB P-type ATPases ATPases Ca2+ transporting ATP2 P(4)-ATPases P4-ATPases Type IV P-type ATPases flippases ATPase phospholipid transporting ATPase H+/K+ transporting ATP7 type IB P-type ATPases ATPase copper transporting ATP7 ATP13 P(5) ATPases P5 ATPases type V P-type ATPases ATPase orphan transporters ATP13 TMBIM Transmembrane BAX inhibitor motif containing TMBIM TCEAL WEX WWbp5-like X-linked Transcription elongation factor A like family TCEAL BEX Brain expressed X-linked family BEX LIM domains are protein structural domains, composed of two contiguous zinc finger domains, separated by a two- amino acid residue hydrophobic linker. They are named after their initial discovery in the proteins L in11, I sl-1 & M ec-3. LIM-domain containing proteins have been shown to play roles in cytoskeletal organisation, organ development and oncogenesis. LIM-domains mediate protein:protein interactions that are critical to cellular processes. LIM domains have highly divergent sequences, apart from certain key residues. The sequence divergence allow a great many different binding sites to be grafted onto the same basic domain. The conserved residues are those involved in zinc binding or the hydrophobic core of the protein. The sequence signature of LIM domains is as follows: - 2-4 -- 13-19 --- 2-4 ----- 2-4 -- 13-20 -C- 2-4 - LIM domain organisation LIM domains frequently occur in multiples, as seen in proteins such as TES, LMO4, and can also be attached to other domains in order to confer a binding or targeting function upon them, such as LIM-kinase. The LIM superclass of genes have been classified into 14 classes: ABLIM, CRP, ENIGMA, EPLIN, LASP, LHX, LMO, LIMK, LMO7, MICAL, PXN, PINCH, TES, and ZYX. Six of these classes (i.e., ABLIM, MICAL, ENIGMA, ZYX, LHX, LM07) originated in the stem lineage of animals, and this expansion is thought to have made a major contribution to the origin of animal multicellularity. LIM domains are also found in various bacterial lineages where they are typically fused to a metallopeptidase domain. Some versions show fusions to an inactive P-loop NTPase at their N-terminus and a single transmembrane helix. These domain fusions suggest that the prokaryotic LIM domains are likely to regulate protein processing at the cell membrane. The domain architectural syntax is remarkable parallel to those of the prokaryotic versions of the B-box zinc finger and the AN1 zinc finger domains. Zinc fingers, LIM-type LIM domain containing Troponin is a complex of three regulatory proteins ( troponin C, troponin I, and troponin T ) that is integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker or therapeutic target for various heart disorders in particular as a highly specific marker for myocardial infarction or heart muscle cell death. TNN Troponin complex subunits TNN The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. PDZ is an acronym combining the first letters of three proteins â€' post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) â€' which were first discovered to share the domain. PDZ domains have previously been referred to as DHR (Dlg homologous region) or GLGF ( glycine - leucine -glycine- phenylalanine ) domains. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. Protein domains, connected by intrinsically disordered flexible linker regions, induce long-range allostery via protein domain dynamics. PDZ domains also play a highly significant role in the anchoring of cell surface receptors (such as CFTR and FZD7 ) to the actin cytoskeleton via mediators like NHERF and ezrin. In general PDZ domains bind to a short region of the C-terminus of other specific proteins. These short regions bind to the PDZ domain by beta sheet augmentation. This means that the beta sheet in the PDZ domain is extended by the addition of a further beta strand from the tail of the binding partner protein. PDZ PDZ domain containing PDZ NOLA H/ACA ribonucleoprotein complex NOLA Crumbs complex crumbs cell polarity complex Crumbs complex components Scribble complex UTPB SSU processome subcomplex bUTP UTPb subcomplex LU (lymphocyte antigen 6-uPAR) proteins LYPD TFP/LY6/uPAR proteins LY6/PLAUR domain containing LYPD HRAS like suppressor family PLA/AT PLAAT Phospholipase A/acyltransferase family lecithin:retinol acyltransferase like Phospholipase A and acyltransferase family PLAAT TOM complex TOMM Translocase of outer mitochondrial membrane complex TOMM BDCPs Beige and Chediak-Higashi domain containing BEACH domain containing BET proteins Bromodomain containing, BET Bromodomain and extra-terminal domain family A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the N-terminal tails of histones. Bromodomains, as the “readers” of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. BRD Bromodomain containing BRD Mannose-6-phosphate receptor homology domain containing MRH domain containing thioester-containing protein superfamily CPAMD I39 protease inhibitor family TED superfamily C3 and PZP like, alpha-2-macroglobulin domain containing CPAMD DGAT2 DGAT2/MOGAT family Diacylglycerol O-acyltransferase 2/monoacylglycerol O-acyltransferase family Diacylglycerol O-acyltransferase 2 family DGAT2 The ASAP complex interacts with the exon-junction complex (EJC), a messenger ribonucleoprotein complex involved in post-transcriptional regulation. The three ASAP subunits (Acinus, RNPS1 and SAP18) have been individually implicated in transcriptional regulation, pre-mRNA splicing and mRNA quality control. ASAP complex subunits EJC Exon junction complex Nonaspanins TM9SF Transmembrane 9 superfamily members TM9SF TPPP Tubulin polymerization promoting proteins TPPP ARR Arrestins ARR EMSY/KDM5A/SIN3B complex EMSY complex The USH2 complex is localized mainly at the periciliary membrane complex in photoreceptors and the ankle-link of the stereocilia in hair cells. ALC ankle link complex USH2 complex DAND DAN family DAND LIG DNA ligases LIG PARbZip proteins represent a subfamily of circadian transcription factors belonging to the bZip family. They are transcriptionally controlled by the circadian molecular oscillator and are suspected to accomplish output functions of the clock. In turn, PARbZip proteins control expression of genes coding for enzymes involved in metabolism, but also expression of transcription factors which control the expression of these enzymes. proline and acidic amino acid–rich basic leucine zipper transcription factors PAR bZIP family PRRG Proline rich and Gla domain containing PRRG Gla proteins gamma-carboxyglutamic acid domain containing vitamin K-dependent carboxylation domain containing Gla domain containing Nesprins Nuclear envelope spectrin repeat proteins SYNE Spectrin repeat containing nuclear envelope family SYNE Scavenger receptors are a group of receptors that recognize modified low-density lipoprotein (LDL) by oxidation or acetylation. This naming is based on a function of cleaning (scavenging): Scavenger receptors widely recognize and take up macromolecules that have a negative charge, like modified LDL. SCAR Scavenger receptors SCAR NF-kappaB ( nuclear factor kappa-light-chain-enhancer of activated B cells ) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-kappaB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-kappaB plays a key role in regulating the immune response to infection (kappa light chains are critical components of immunoglobulins). Incorrect regulation of NF-kappaB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-kappaB has also been implicated in processes of synaptic plasticity and memory. NF-kB complex subunits NF-kB family Rel/NF-kB family NF-kappa B complex subunits Sm and like-Sm (LSm) proteins belong to an ancient family of RNA-binding proteins represented in all three domains of life. Members of this family form ring complexes on specific sets of target RNAs and have critical roles in their biogenesis, function and turnover. These proteins are a part of several small nucleolar ribonucleoprotein complexes (snRNPs) involved in pre-mRNA splicing. SNRP Sm core proteins Smith antigens Sm spliceosomal proteins SNRP FOS Fos transcription factor family FOS JUN Jun transcription factor family JUN AP-1 transcription factor subunits SNAG zinc fingers Snai/Gfi family SNAG transcriptional repressors RGK type GTPase family These genes encode proteins containing a CysCysHisHisCys (CCHHC) type zinc finger domain. The CCHHC-type zinc finger contains five absolutely conserved cysteine and histidine residues (rather than the more usual four) with the sequence C-P-x-P-G-C-x-G-x-G-H-x(7)-H-R-x(4)-C. The second histidine has been shown to coordinate Zn(II) along with the three cysteines residues. The first His plays a different role in stabilizing the structure, stacking between the metal-binding core and an aromatic residue that is relatively conserved. CCHHC-type zinc fingers form small compact structures that can sit entirely within the major groove of DNA (<a href='https://pubmed.ncbi.nlm.nih.gov/18073212/'>PMID: 18073212</a>),(<a href='https://pubmed.ncbi.nlm.nih.gov/24097990/'>PMID: 24097990</a>), (<a href='https://pubmed.ncbi.nlm.nih.gov/25098749/'>PMID: 25098749</a>), (<a href='https://pubmed.ncbi.nlm.nih.gov/26158299/'>PMID: 26158299</a>), (<a href='https://pubmed.ncbi.nlm.nih.gov/14744132/'>PMID: 14744132</a>). CCHHC-type zinc fingers Myt1 transcription factor family Neural zinc finger transcription factor family Zinc fingers C2H2C-type MBT domain containing IL-6 family Interleukin 6 family Interleukin 6 type cytokine family Protein phosphatase 2 modulatory subunits PPP2R1 Protein phosphatase 2 scaffold subunits PPP2R1 VEGF VEGF family VEGF ERCC ERCC excision repair associated ERCC Nucleotide excision repair KHDRBS STAR family Signal transduction and activation of RNA metabolism family KHDRBS AMEX complex Anchoring and mRNA export complex TREX-2 complex Transcription and export complex 2 The BH3-only subset of the Bcl-2 family of proteins contain only a single BH3-domain. The BH3-only members play a key role in promoting apoptosis. The BH3-only family members are Bim, Bid, BAD and others. Various apoptotic stimuli induce expression and/or activation of specific BH3-only family members, which translocate to the mitochondria and initiate Bax/Bak-dependent apoptosis. BCL2 homology region 3 (BH3) only secreted protein acidic and rich in cysteine family SPARC family Small integrin binding ligand N-linked glycoprotein family SIBLING family The super elongation complex (SEC) consists of the RNA polymerase II (Pol II) elongation factors eleven-nineteen Lys-rich leukaemia (ELL) proteins, positive transcription elongation factor b (P-TEFb) and several frequent mixed lineage leukaemia (MLL) translocation partners. It is one of the most active P-TEFb-containing complexes required for rapid transcriptional induction in the presence or absence of paused Pol II. The SEC was found to regulate the transcriptional elongation checkpoint control (TECC) stage of transcription, and misregulation of this stage is associated with cancer pathogenesis. SEC Super elongation complex The positive transcription elongation factor, P-TEFb, plays an essential role in the regulation of transcription by RNA polymerase II (Pol II) in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes. P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol II and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP. Treatment of cells with the P-TEFb inhibitors DRB or flavopidirol leads to loss of mRNA production and ultimately cell death. PTEFb complex cyclin T/CDK9 complex positive transcription elongation factor b P-TEFb complex subunits MAPR family Membrane associated progesterone receptor family The YEATS family are named after the genes first found to share this domain: 'YNK7', `ENL', `AF-9', and `TFIIF small subunit'. All these proteins are thought to have a transcription stimulatory activity. YEATS domain containing NUDC NudC family NUDC I-BAR modules preferentially bind to membrane surfaces of a negative curvature. I-BARs are also capable of deforming membranes and inducing plasma membrane protrusions IMD domain containing IRSp53-MIM homology domain containing I-BAR domain containing The F-BAR domain, also known as the extended FCH domain (EFC) in PCH family proteins includes the FCH domain and CC region and is only weakly similar to the BAR domain. By sequence alignment, structural, biochemical and cell biological studies, it has been shown that the EFC is actually an extended BAR domain, and that F-BAR domains share similar properties with BAR domains. The F-BAR domain plays a role in dimerization and membrane phospholipid binding. EFC domain containing Extended FCH homology domain containing FCH-BAR domain containing Fes/CIP4 homology BAR domain containing Pombe/Cdc15 homology family F-BAR domain containing The BAR-domain homodimer displays a crescent shape that binds to the membrane bilayer with its concave side. In addition, an N-terminal amphipathic helix is thought to insert into the membrane like a 'wedge', thereby inducing membrane buckling. N-terminal BAR domain containing N-terminal amphipathic helices BAR domain containing N-BAR domain containing PX domain proteins bind phosphoinositides and participate in membrane remodeling and trafficking events. PX-BAR domain containing BAR-pleckstrin homology domain containing BAR-PH domain containing BAR domain containing AH/BAR superfamily In molecular biology, the FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin ) is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal -associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus in the majority of proteins in which it is found. Band 4.1 homologs ERM domain containing Four-point-one, ezrin, radixin, moesin domain containing FERM domain containing SPOUT methyltransferase domain containing PRELID Protein of Relevant Evolutionary and Lymphoid Interest Domain containing PRELI domain containing PRELID Toll/interleukin-1 receptor homology domain containing TIR domain containing A C-type lectin (CLEC) is a type of carbohydrate-binding protein domain known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis. CLEC C-type lectin domain containing CLEC BNIP-2 and Cdc42GAP homology domain containing BCH domain containing An aminoacyl tRNA synthetase ( aaRS ) is an enzyme that catalyzes the esterification of a specific amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In other words, aminoacyl tRNA synthetase simply attaches the appropriate, or 'cognate,' amino acid onto the corresponding tRNA. This is sometimes called 'charging' or 'loading' the tRNA with the amino acid. Once the tRNA is charged, a ribosome can transfer the amino acid from the tRNA onto a growing peptide, according to the genetic code. aaRS Aminoacyl tRNA synthetases MIA melanoma inhibitory activity family MIA family MIA This complex contains the mammalian homologs of the budding yeast Rix1 complex. It links arginine methylation to desumoylation and is important for ribosomal maturation. Five Friends of Methylated Chtop complex LAS1L complex PELP1-TEX10-WDR18 complex SENP3 associated protein complex Large ribosomal subunit biogenesis complex Adenosine deaminase family ADA Adenosine deaminases acting on RNA ADA In the field of molecular biology, the Mi-2NuRD was the only known protein complex coupling chromatin remodeling ATPase and chromatin deacetylation enzymatic functions. The NuRD complex contains seven subunits: the histone deacetylase core proteins HDAC1 and HDAC2, the histone-binding proteins RbAp46 and RbAp48, the metastasis-associated proteins MTA1 (or MTA2 / MTA3 ), the methyl-CpG-binding domain protein MBD3 (or MBD2 ) and the chromodomain-helicase-DNA-binding protein CHD3 (aka Mi-2alpha) or CHD4 (aka Mi-2beta). The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves reprogramming efficiency, that results in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells). Mi2/NURD complex NuRD complex subunits Mammalian genomes encode two homologs of SIN3 (SIN3A/B), which associate individually with HDAC1 and HDAC2, RBBP4 and RBBP7, SDS3, and the SIN3-associated proteins SAP18 and SAP30 to form the core SIN3 complex. Different studies have identified additional interaction partners including MeCP2 (methyl-CpG-binding protein), RBP1 (RB-binding protein), BRMS1 (breast cancer metastasis suppressor), ING1/2 (inhibitor of growth), SAP25, SAP130, and SAP180, as well as the histone demethylase RBP2/KDM5A (Hayakawa and Nakayama, 2011 and Kadamb et al., 2013). SIN3-HDAC complex SIN3-HDAC1 complex SIN3 histone deacetylase complex subunits The mammalian BTG/Tob family gene products have anti-proliferative ability and are characterised by a conserved BTG domain. Tob subfamily members have the most extensive C-terminal regions. The BTG domain mediates interactions with the highly similar Caf1a (CNOT7) and Caf1b (CNOT8) catalytic subunits of the Ccr4-Not deadenylase complex. Overexpression of BTG/Tob proteins is associated with the inhibition of G1 to S-phase cell cycle progression and decreased cell proliferation in a variety of cell types. APRO family BTG/Tob family Aminoacyl tRNA synthetases, Class I Alpha-arrestins have highly conserved PPxY motifs, which allow binding to WW domains in proteins such as ubiquitin ligases. Several α-arrestins play prominent roles in the regulation of metabolism. ARRDC Alpha arrestins ARRDC ARR Beta arrestins Visual arrestins Classical arrestins ARR EKC complex Kinase Endopeptidase and Other proteins of Small size complex KEOPS complex Fezzins LZTS Leucine zipper tumor suppressor family LZTS PSG Pregnancy specific glycoproteins PSG The Nuclear Exosome Targeting (NEXT) complex is a key cofactor of the mammalian nuclear exosome in the removal of Promoter Upstream Transcripts (PROMPTs) and potentially aberrant forms of other noncoding RNAs, such as snRNAs. NEXT displays preference for U-rich pyrimidine sequences and this RNA binding is mediated by the RNA recognition motif (RRM) of the RBM7 subunit. NEXT complex Nuclear exosome targeting complex Carcinoembryonic antigen family Polyadenylation of mitochondrial RNAs in higher eukaryotic organisms have diverse effects on their function and metabolism. Polyadenylation completes the UAA stop codon of a majority of mitochondrial mRNAs in mammals, regulates the translation of the mRNAs, and has diverse effects on their stability. The addition of a poly(A) tail is catalyzed by poly(A) polymerases (PAPs). Nuclear PAPs that are involved in the 3′-end processing of pre-mRNAs have been studied extensively over the years. More recently, a collection of non-canonical PAPs (ncPAPs) has been identified, which are involved in polyadenylation in other organelles (as well as in the nucleus). Some of these ncPAPs have relaxed base selectivity and can also synthesize oligo- or poly-uridylate tails, and hence are also known as poly(U) polymerases (PUPs) or terminal uridylate transferases (TUTs or TUTases). TUTases Non-canonical poly(A) polymerases Aminoacyl tRNA synthetases, Class II In response to DNA damage, cells activate a complex signal transduction network called the DNA damage response (DDR). TTI1 (Tel two-interacting protein 1) and TTI2 are highly conserved regulators of the DDR in mammals, protect cells from spontaneous DNA damage and are required for the establishment of the intra-S and G2/M checkpoints. TTI1 and TTI2 exist in multiple complexes, including a 2-MDa complex with TEL2 (telomere maintenance 2), called the Triple T complex, and phosphoinositide-3-kinase-related protein kinases (PIKKs) such as ataxia telangiectasia-mutated (ATM). The components of the TTT complex are mutually dependent on each other, and act as critical regulators of PIKK abundance and checkpoint signaling. Triple T complex TTT complex A carboxypeptidase ( EC number 3.4.16 - 3.4.18) is a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide. (Contrast with an aminopeptidase, which cleaves peptide bonds at the other end of the protein.) Humans, animals, and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation. CP M14 carboxypeptidases CP During mitosis, the spindle checkpoint senses kinetochores not properly attached to spindle microtubules and prevents precocious sister-chromatid separation and aneuploidy. The constitutive centromere-associated network (CCAN) at inner kinetochores anchors the KMN network consisting of Knl1, the Mis12 complex (Mis12C), and the Ndc80 complex (Ndc80C) at outer kinetochores. MIS12 kinetochore complex The STEAP proteins are essential transmembrane metalloreductases that facilitate the reduction of copper and iron. STEAP six transmembrane epithelial antigen of the prostate family STEAP family STEAP The synapsins are a family of proteins that have long been implicated in the regulation of neurotransmitter release at synapses. Specifically, they are thought to be involved in regulating the number of synaptic vesicles available for release via exocytosis at any one time. Synapsins are present in invertebrates and vertebrates and are somewhat homologous across evaluated vertebrates. Current studies suggest the following hypothesis for the role of synapsin: synapsins bind synaptic vesicles to components of the cytoskeleton which prevents them from migrating to the presynaptic membrane and releasing neurotransmitter. During an action potential, synapsins are phosphorylated by PKA (cAMP dependent protein kinase), releasing the synaptic vesicles and allowing them to move to the membrane and release their neurotransmitter. Gene knockout studies in mice (where the mouse is unable to produce synapsin) have had some surprising results. Mice lacking all three synapsins are prone to seizures, and experience learning defects. These results suggest that while synapsins are not essential for synaptic function, they do serve an important modulatory role. Conversely, studies using transgenic mice in which neuronal signaling is abolished in specific circuitries showed that synaptic activity regulates, but is not essential to maintain, the expression of these proteins. SYN Synapsins SYN Caveolae are specialized plasma membrane domains that form flask-shaped invaginations. They are involved in cell signalling and transport and have been shown to critically regulate metabolism and vascular permeability and blood pressure. The organization and functions of caveolae are mediated by coat proteins called caveolins (Caveolin1-3) and cavins (Cavin1-4). CAVIN PTRF/SDPR family Cavins CAVIN This complex is critical for BRCA1 recruitment to the sites of DNA damage. BRCA1-Rap80 complex BRCA1 A complex The SRCAP complex remodels chromatin by catalyzing the incorporation of H2AZ-H2B dimers into nucleosomes. The SRCAP complex also plays a role in DSB resection and HR, hence contributing to cell survival upon exposure to DNA damage-inducing agents. SRCAP complex Protein kinases of the Casein Kinase 1 family play a vital role in the regulation of numerous cellular processes. Apart from functions associated with regulation of proliferation, differentiation, or apoptosis, localization of several Casein Kinase 1 isoforms to the centrosome and microtubule asters also implicates regulatory functions in microtubule dynamic processes. Being localized to the spindle apparatus during mitosis Casein Kinase 1 directly modulates microtubule dynamics by phosphorylation of tubulin isoforms. CK1 family CSNK Casein kinase 1 family CSNK This is an actin-regulating complex that is recruited to endosomes by interactions with the retromer complex and plays a role in endosomal sorting. Wiskott–Aldrich syndrome protein and SCAR homolog complex WASH complex mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrientredox sensor and controls protein synthesis. This complex embodies the classic functions of mTOR, namely as a nutrient/energy/redox sensor and controller of protein synthesis. The activity of this complex is regulated by rapamycin, insulin, growth factors, phosphatidic acid, certain amino acids and their derivatives (e.g. L -leucine and β-hydroxy β-methylbutyric acid ), mechanical stimuli, and oxidative stress. The role of mTORC1 is to activate translation of proteins. In order for cells to grow and proliferate by manufacturing more proteins, the cells must ensure that they have the resources available for protein production. Thus, for protein production, and therefore mTORC1 activation, cells must have adequate energy resources, nutrient availability, oxygen abundance, and proper growth factors in order for mRNA translation to begin. TOR complex 1 mTORC1 mammalian target of rapamycin complex 1 mechanistic target of rapamycin complex 1 MTOR complex 1 mTOR Complex 2 ( mTORC2 ) is a protein complex that regulates cellular metabolism as well as the cytoskeleton. TOR complex 2 mTORC2 mammalian target of rapamycin complex 2 mechanistic target of rapamycin complex 2 MTOR complex 2 Shelterin (also called telosome ) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as regulate telomerase activity. In mammals and other eukaryotes, telomeric DNA consists of double- and single-stranded TTAGGG repeats and a single-stranded, G-rich overhang. Subunits of shelterin bind to these regions and induce the formation of a t-loop, a cap structure that deters DNA-damage-sensing machinery from mistakenly repairing telomeres. The absence of shelterin causes telomere uncapping and thereby activates damage-signaling pathways that may lead to non-homologous end joining (NHEJ), homology directed repair (HDR), senescence, or apoptosis. telosome complex Shelterin complex The BRCA1-B complex is involved in DNA replication stress-induced checkpoint and DNA interstrand crosslink (ICL) repair BRCA1 B complex BRCA1 forms a complex with RBBP8 and MRN (MRE11/RAD50/NBN) in a cell cycle-dependent manner during S and G2 phase of the cell cycle through the BRCT domains of BRCA1 binding to phosphorylated S327, a CDK phosphorylation site of RBBP8 in a phospho-SPxF motif. The <a href='http://www.genenames.org/data/genegroup/#!/group/1344'>MRN complex</a> also has other functions not related to its role in the BRCA1 C complex. RBBP8 is required for DNA end resection at the initial step of homologous recombination (HR) dependent DSB repair CTIP promotes DNA end resection by interacting and stimulating the nuclease activity of the MRN complex. The complex formation of BRCA1-RBBP8-MRN is important for facilitating DSB resection to generate single-stranded DNA that is needed for HR-mediated DSB repair. BRCA1 C complex TIM22 complex CPC Chromosomal passenger complex 9-1-1 checkpoint clamp DNA damage response clamp 9-1-1 Checkpoint clamp complex complex II Ripoptosome The apoptosome is a large quaternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death stimulus. Stimuli can vary from DNA damage and viral infection to developmental cues such as those leading to the degradation of a tadpole's tail. In mammalian cells, once cytochrome c is released, it binds to the cytosolic protein Apaf-1 to facilitate the formation of apoptosome. An early biochemical study suggests a two-to-one ratio of cytochrome c to apaf-1 for apoptosome formation. However, recent structural studies suggest the cytochrome c to apaf-1 ratio is one-to-one. It has also been shown that the nucleotide dATP as third component binds to apaf-1, however its exact role is still debated. The mammalian apoptosome had never been crystallized, but a human APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm ) resolution by cryogenic transmission electron microscopy 10 years ago, revealing a wheel-like particle with 7-fold symmetry. Recently, a medium resolution (9.5 Ã…ngström) structure of human apoptosome was also solved by cryo-electron microscopy, which allows unambiguous inference for positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. There is also now a crystal structure of the monomeric, inactive Apaf-1 subunit (PDB 3SFZ). Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. Once activated, this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. Apoptosome The death-inducing signaling complex or DISC is a multi-protein complex formed by members of the 'death receptor' family of apoptosis -inducing cellular receptors. A typical example is FasR, which forms the DISC upon trimerization as a result of its ligand ( FasL ) binding. The DISC is composed of the death receptor, FADD, and caspase 8. It transduces a downstream signal cascade resulting in apoptosis. The Fas ligands, or cytotoxicity-dependent APO-1-associated proteins, physically associate with APO-1 (also known as the Fas receptor, or CD95), a tumor necrosis factor containing a functional death domain. This association leads to the formation of the DISC, thereby inducing apoptosis. The entire process is initiated when the cell registers the presence of CD95L, the cognate ligand for APO-1. Upon binding, the CAP proteins and procaspase-8 (composed of FLICE, MACH, and Mch5) bind to CD95 through death domain and death effector domain interactions. Procaspase-8 activation is thought to occur through a dimerization process with other procaspase-8 molecules, known as an induced proximity model. The CAP proteins associate only with the oligomerized version of APO-1 when forming the complex. The CAP1 are CAP2 proteins are also known as FADD/MORT1, an adaptor molecule with a death domain. CAP4 is also called FLICE, a cysteine protease with two death effector domains. CAP3 is the prodomain of FLICE generated during proteolytic activation. Once the DISC assembles, it allows APO-1 signaling to occur, which triggers cell death. In order to do this, downstream targets such as FLICE must be activated. In its inactive state, FLICE's two death domains are thought to bind together and prevent its activation. Once APO-1 aggregates within the cytosol, it recruits FADD, CAP3, and FLICE to the receptor, where FLICE is modified into several active subunits, which have the ability to cleave a variety of substrates. This proteolytic activity then results in a cascade of caspase activation, and ultimately cell death. This apoptotic activity is critical for tissue homeostasis and immune function. APO-1-mediated apoptosis can be inhibited by a variety of factors, including the viral caspase inhibitors CrmA and p35, as well as viral FLICE-inhibitory proteins known as v-FLIPs. When in the presence of APO-1, v-FLIPs preferentially bind and prevent procaspase-8 from being recruited; as such, apoptosis is stalled. Interestingly, humans have a homolog for v-FLIP known as c-FLIP, which occurs in two endogenous forms (c-FLIPL (long) and c-FLIPS (short)). These are similar in structure to procaspase-8, but lack the amino acids necessary for caspase-8 catalytic activity. It is thought that c-FLIP may be involved in modulating the immune system, as c-FLIPS is upregulated upon stimulation of the T cell receptor. Furthermore, as high expression of FLIP is known to promote tumor growth, these inhibitor molecules play a role in cancer proliferation. The DISC has been implicated as a possible drug development target for various cancers, including leukemia, glioma, and colon cancer. In glioma cells, the effects of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) have been shown to induce DISC-mediated apoptosis. Specifically, TRAIL works by activating two death receptors, DR4 and DR5; these bind to FADD, which then interacts with caspase-8 to assemble the DISC. Tumor cells show varying sensitivity to TRAIL modulated apoptosis, depending on the presence of the antiapoptotic FLIP proteins. Additionally, studies in leukemia have indicated that the histone deacetylase inhibitor LAQ824 increases apoptosis by decreasing the expression levels of the c-FLIPs. As such, these inhibitors are promising targets for anti-cancer therapy. DISC Death inducing signaling complex The CST complex localizes specifically to single-stranded telomeric DNA, including the telomeric overhang. In yeast this complex is involved in chromosome end capping and telomere length regulation. The capping properties of CST may be dispensable in vertebrates in vivo due to the presence of the shelterin complex, which also caps chromosome ends. There is evidence to suggest that the CST complex rescues stalled replication forks under conditions of replication stress. CST complex The MRN complex (MRX complex in yeast) is a protein complex consisting of Mre11, Rad50 and Nbs1 (also known as Nibrin in humans and as Xrs2 in yeast). In eukaryotes, the MRN/X complex plays an important role in the initial processing of double-strand DNA breaks prior to repair by homologous recombination or non-homologous end joining. The MRN complex binds avidly to double-strand breaks both in vitro and in vivo and may serve to tether broken ends prior to repair by non-homologous end joining or to initiate resection prior to repair by homologous recombination. The MRN complex also participates in activating the checkpoint kinase ATM in response to DNA damage. Production of short single-strand oligonucleotides by Mre11 endonuclease activity has been implicated in ATM activation by the MRN complex. MRN complex tRNA maturation involves an intron splicing and an exon ligation step. The product of RTCB is the catalytic subunit of the human tRNA ligation complex. Full enzymatic activity of RTCB depends on guanylation, which is provided by the co-factor ZBTB8OS (archease) working in cooperation with DDX1. tRNA splicing ligase complex The protein products of these genes catalyze the oxidation of proteins (for TYW5 a tRNA) to stable hydroxylated products. JmjC hydroxylases in general appear to have more open binding sites than the KDMs and bind their target residues primarily through main and side chain hydrogen bonds, rather than the principally hydrophobic interactions used by KDMs. Jumonji-C domain-containing oxygenases cupin 8 domain containing hydroxylases protein/nucleic acid hydroxylases JmjC hydroxylases The Polycomb Repressive Complex 2 (PRC2) is a key chromatin modifier involved in the maintenance of transcriptional silencing. The proteins encoded by EZH1 and EZH2 are the two paralogous enzymatic subunits of the complex and the proteins encoded by SUZ12 and EED are strictly required for their enzymatic activity. The RBBP4/7 paralogs, which are believed to contribute to nucleosome binding, are also part of other chromatin regulatory complexes. PRC2 Polycomb repressive complex 2 The TREX complex couples transcription elongation by RNA polymerase II to mRNA export, moving along the gene with the elongating polymerase during transcription. It acts as a binding platform for the protein product of NXF1 (nuclear RNA export factor 1). TREX subunits are also involved in piRNA transcription and biogenesis. The TREX complex also helps prevent R-loop formation during transcription. THO-TREX complex TREX complex TREX/THO complex Transcription export complex Transcription and export complex 1 subunits These genes encode proteins that contain Glycine-arginine-phenylalanine (GRF)-type zinc fingers (GRF-ZFs), 45- to 50-residue domains with a conserved GRxF motif. GRF-ZFs are widely distributed throughout eukaryotes in proteins that are involved in DNA damage response (DDR), transcriptional regulation, and RNA metabolism. GRF-ZFs are nucleic acid interaction modules and in several cases these motifs have been shown to enhance enzymatic activity. This domain comprises a three-stranded anti-parallel β-sheet that folds into a crescent-shaped claw-like structure (5U6Z). A single bound Zn(2+) ion plays a central structural role in this domain, and is coordinated with tetrahedral geometry by a 'CHCC' sequence motif. GRF zinc fingers Glycine-arginine-phenylalanine (GRF)-type zinc fingers ZGRF zf-GRF Zinc fingers GRF-type ZGRF The S100 fused type protein (SFTP) family or fused gene family encompasses genes which are mainly expressed in stratified epithelia and play a role in epithelial homeostasis. Like S100 proteins, SFTPs contain two calcium-binding EF-hand motifs. These proteins are associated with cytoplasmic intermediate filaments as well as minor components of the CE. Due to their homologous structure they are also known as filaggrin-like proteins. SFTP family S100 fused type protein family As it name implies, the cornified envelope (CE) precursor family includes genes that encode the proteins forming the CE. The CE is a cross-linked matrix that surrounds terminally differentiated squamous keratinocytes after a process known as cornification. CE precursor proteins are cross-linked by transglutaminases. The ratio of CE precursor proteins varies from tissue to tissue. In the epidermis, the most abundant CE component is loricrin (65-70%), while involucrin is a minor component (<5%). Cornified envelope precursor family SPRR genes encode proteins that are strongly induced during differentiation of human epidermal keratinocytes in vitro and in vivo and are a class of cornified envelope precursor proteins. The structure of the central segments of the encoded proteins are built up from tandemly repeated units of either eight (SPRR1 and SPRR3) or nine (SPRR2) amino acids with the general consensus *K*PEP**. SPRR Small proline rich proteins SPRR The epidermal differentiation complex ( EDC ) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the complex is located on a 1.9 Mbp stretch within chromosome 1q 21. The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct gene families : the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP) family. It has been hypothesized that the clustering of EDC genes occurred due to duplication events which were evolutionarily favored during the adaptation to terrestrial environments. EDC proteins have been involved in a variety of skin disorders including ichthyosis vulgaris, atopic dermatitis and psoriasis. EDC Epidermal differentiation gene complex Epidermal differentiation complex Cysteine-rich secretory proteins, often abbreviated as CRISPs, are a group of glycoproteins. They are a subgroup of the CRISP, antigen 5 and Pr-1 ( CAP ) protein superfamily and are substantially implicated in the functioning of the mammalian reproductive system. CRISPs are also found in a variety of snake venoms where they inhibit both smooth muscle contraction and cyclic nucleotide-gated ion channels. CRISP CRISPs Cysteine rich secretory protein family CRISP The CAP superfamily ( cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins (CAP)) is a large superfamily of secreted proteins that are produced by a wide range of organisms, including prokaryotes and non- vertebrate eukaryotes. Members are most often secreted and have an extracellular endocrine or paracrine function and are involved in processes including the regulation of extracellular matrix and branching morphogenesis, potentially as either proteases or protease inhibitors; in ion channel regulation in fertility ; as tumour suppressor or pro- oncogenic genes in tissues including the prostate ; and in cell-cell adhesion during fertilisation. The overall protein structural conservation within the CAP superfamily results in fundamentally similar functions for the CAP domain in all members, yet the diversity outside of this core region dramatically alters the target specificity and, thus, the biological consequences. CRISP, antigen 5 and Pr-1 (CAP) protein superfamily SCP/TAPS (Sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily cysteine rich secretory proteins, antigen 5, and pathogenesis related 1 proteins superfamily sperm-coating glycoprotein (SCP) family CAP superfamily GLI pathogenesis-related family GLIPR related to testis specific, vespid and pathogenesis related 1 (RTVP1) proteins GLIPR family GLIPR In anatomy, a crystallin is a water-soluble structural protein found in the lens and the cornea of the eye accounting for the transparency of the structure. It has also been identified in other places such as the heart, and in aggressive breast cancer tumors. Since it has been shown that lens injury may promote nerve regeneration, crystallin has been an area of neural research. So far, it has been demonstrated that crystallin beta B2 (CRYBB2) may be a neurite -promoting factor. Betagamma crystallin superfamily CRYB, CRYG Beta-gamma crystallins CRYB, CRYG This domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to non-methylated CpG dinucleotides. The domain is characterised by two CGXCXXC repeats. The RecQ helicase has a single repeat that also binds to zinc, but this has not been included in this family. The DNA binding interface has been identified by NMR. CXXC zf-CXXC Zinc fingers CXXC-type CXXC The proteins encoded by these genes contain six beta-gamma crystallin like domains encoded in exons arranged like those in beta crystallin genes. The proteins encoded by these genes do not serve as crystallins. Beta-gamma crystallin domain containing NTC/Prp19C was discovered as a complex that functions in splicing and more specifically during the catalytic activation of the spliceosome. More recent work revealed that NTC/Prp19C plays a role in transcription elongation in Saccharomyces cerevisiae and in genome maintenance in higher eukaryotes. NTC complex PRP19 complex PRP19-CDC5L complex PRP19C PRPF19 complex PSO4 core complex NineTeen complex Nucleosome Remodeling Factor (NURF) is an ATP-dependent chromatin remodeling complex that catalyzes nucleosome sliding in order to regulate gene transcription. It contains an ISWI ATPase (SMARCA1), making it part of the ISWI family of chromatin remodeling complexes. NURF is highly conserved among eukaryotes and is involved in transcriptional regulation of developmental genes. NuRF chromatin remodeling complex Nucleosome Remodeling Factor complex NURF complex The Integrator complex associates with phosphorylated RNA polymerase II (RNAPII). This complex processes the 3′ end of the U-rich small nuclear RNA (snRNA). INTS Integrator complex INTS 2-Oxoglutarate dependent oxygenases 2OG oxygenases 2OGXs Iron (II) and 2-oxoglutarate dependent oxygenases DCDC DCX superfamily Doublecortin superfamily DCDC These genes encode proteins containing a domain with several pairs of CxxC motifs, referred to as 3CxxC-type zinc finger which is found in 3CxxC-type zinc finger proteins, such as zygote arrest protein 1 (ZAR1) and its homologues, ZAR1-like proteins, and receptor-transporting proteins 1-5 (RTP1-5). Only one pair of cysteines is associated with a highly conserved histidine residue. Z3CXXC ZAR1/RTP1-5-like zinc fingers zf-3CxxC Zinc fingers 3CxxC-type Z3CXXC striatin-interacting phosphatase and kinase complex STRIPAK complex C1QTNF CTRP family C1q and TNF related C1QTNF Hedgehog signaling molecule family The TLC domain is also known as the TRAM/LAG1/CLN8 homology domain (IPR006634). InterPro describes the domain and family members as follows: TLC is a protein domain with at least 5 transmembrane alpha-helices. Lag1p and Lac1p [yeast proteins] are essential for acyl-CoA-dependent ceramide synthesis [PMID: 11694577], TRAM1 is a subunit of the translocon and the CLN8 gene is mutated in Northern epilepsy syndrome. Proteins containing this domain may possess multiple functions such as lipid trafficking, metabolism, or sensing. Trh homologues [e.g. the CERS class homeobox class family in humans] possess additional homeobox domains [PMID: 9872981]. TRAM/LAG1/CLN8 homology domain TLC domain containing The BRCC36 isopeptidase complex (BRISC) is a Deubiquitinating enzyme (DUB) that is specific for lysine 63-linked ubiquitin hydrolysis. The BRISC complex regulates the assembly of the mitotic spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). BRCC36 (BRCC3) isopeptidase complex BRISC complex MINDY family DUBs are highly selective at cleaving K48-linked polyUb, a signal that targets proteins for degradation. MINDY motif interacting with Ub-containing novel DUB family MINDY deubiquitinases MINDY HDHD Haloacid dehalogenase like hydrolase domain containing HDHD MT-RNR Mitochondrial rRNAs Mitochondrially encoded ribosomal RNAs MT-RNR cytoplasmic rRNAs Cytoplasmic ribosomal RNAs The 5S ribosomal RNA (5S rRNA) is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life (bacteria, archaea, and eukaryotes), with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation velocity in an ultracentrifuge, which is measured in Svedberg units (S). 5S rRNAs RNA5S RNAs, 5S ribosomal 5S ribosomal RNAs RNA5S The genes encoding the rRNA components of the ribosome are organized as tandem rDNA repeating units, designated RNR1 through RNR5, in the p12 region of chromosomes 13, 14, 15, 21 and 22. Each rDNA unit encodes a 45S rRNA which serves as the precursor for an 18S, 5.8S and 28S rRNA. The number of rDNA repeating units varies between individuals and from chromosome to chromosome, although usually 30 to 40 repeats are found on each chromosome. [Note that the clusters are extremely difficult to sequence and are therefore not represented on the reference genome assembly. This is why the chromosomal location for each cluster includes the term 'not on reference assembly'] 45S rDNA clusters RNA, ribosomal 45S clusters RNR Ribosomal 45S RNA clusters RNR The sequences coding for ribosomal RNAs are present as rDNA repeating units, designated RNR1 through RNR5, in the p12 region of chromosomes 13, 14, 15, 21 and 22. A 45S rRNA which serves as the precursor for the 18S, 5.8S and 28S rRNA, is transcribed from each rDNA unit by RNA polymerase I. The number of rDNA repeating units varies between individuals and from chromosome to chromosome, although usually 30 to 40 repeats are found on each chromosome. [Note that the clusters are extremely difficult to sequence and are therefore not represented on the reference genome assembly. Each gene symbol below is representative of one 45S pre-ribosomal RNA repeat unit per repeat cluster] 45S rDNA repeats RNA45S RNAs, 45S pre-ribosomal 45S pre-ribosomal RNAs RNA45S 18 S ribosomal RNA (abbreviated 18S rRNA) is a part of the ribosomal RNA. The S in 18S represents Svedberg units. 18S rRNA is a component of the small eukaryotic ribosomal subunit (40S). 18S rRNA is the structural RNA for the small component of eukaryotic cytoplasmic ribosomes, and thus one of the basic components of all eukaryotic cells. It is the eukaryotic nuclear homologue of 16S ribosomal RNA in Prokaryotes and mitochondria. 18S rRNAs RNA18S RNAs, 18S ribosomal 18S ribosomal RNAs RNA18S In molecular biology the 5.8S ribosomal RNA (5.8S rRNA) is a non-coding RNA component of the large subunit of the eukaryotic ribosome and so plays an important role in protein translation. It is transcribed by RNA polymerase I as part of the 45S precursor that also contains 18S and 28S rRNA. Its function is thought to be in ribosome translocation. It is also known to form covalent linkage to the p53 tumour suppressor protein. RNA5-8S 5.8S ribosomal RNAs RNA5-8S 28S ribosomal RNA is the structural ribosomal RNA (rRNA) for the large component, or large subunit (LSU) of eukaryotic cytoplasmic ribosomes, and thus one of the basic components of all eukaryotic cells. It is the eukaryotic nuclear homologue of the prokaryotic 23S and mitochondrial 16S ribosomal RNAs. 28S rRNAs RNA28S RNAs, 28S ribosomal 28S ribosomal RNAs RNA28S MCIA complex Mitochondrial complex I assembly complex Src family kinase is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail Src family kinases interact with many cellular cytosolic, nuclear and membrane proteins, modifying these proteins by phosphorylation of tyrosine residues. A number of substrates have been discovered for these enzymes. Deregulation, including constitutive activation or over expression, may contribute to the progression of cellular transformation and oncogenic activity SFK Src family tyrosine kinases Receptors which transduce extracellular signals across the cell membrane. At the external side they receive a ligand (a photon in the case of opsins), and at the cytosolic side they activate a guanine nucleotide-binding (G) protein. These receptors are hydrophobic proteins that cross the membrane seven times. 7TM receptors G protein coupled receptors GPCR GPCRs GPR Seven-transmembrane domain receptors G protein-coupled receptors LUBAC Linear ubiquitin chain assembly complex RBR RING-BetweenRING-RING E3 ubiquitin ligases TRIAD two RING fingers and a DRIL two RING fingers and a double RING finger linked RBR E3 ubiquitin ligases The Elongin complex is a positive regulator of RNA polymerase II and and increases the rate of elongation by suppressing transient pausing along the DNA template. It is composed of a transcriptionally active subunit (A) and two regulatory subunits (B and C). The Elongin BC complex enhances the transcriptional activity of Elongin A. The Elongin BC complex also acts as an adaptor connecting cullins and SOCS box proteins. ELO SIII complex transcription elongation factor SIII complex Elongin complex ELO KICSTOR complex Gap Activity TOward Rags 1 GATOR1 subcomplex GTPase activating proteins toward Rags subcomplex 2 GATOR2 subcomplex GTPase activating proteins toward Rags complex GATOR complex PGLYRP Peptidoglycan recognition proteins PGLYRP Please note, there are overlaps between the methyltransferase 'sorted by structure' and 'sorted by function' groupings. All methyltransferase group members are represented in the structural hierarchy. Methyltransferase families SET SET domain containing SET WASP family Wiskott-Aldrich Syndrome protein family Rhodopsin-like receptors are a family of proteins that comprise the largest group of G protein-coupled receptors. GPCR Family A GPCRA Rhodopsin receptor family Rhodopsin-like receptors G protein-coupled receptors, Class A rhodopsin-like 7BS methyltransferase motif containing Seven-beta-strand methyltransferase motif containing R2TP chaperone complex R2TP/HSP90 co-chaperone complex R2TP complex Zyxin family Ajuba family Scavenger receptor cysteine rich domain containing CARD11-BCL10-MALT1 (CBM) signalosome complex CBM signalosome CBM complex REL RELT family REL myocardin SRF coactivators myocardin serum response factor coactivators Myocardin family GATD Glutamine amidotransferase class 1 domain containing GATD The genes of this family have undergone major structural and functional changes that benefit their hosts during a process called domestication, generating new genes or regulatory factors and contributing to evolutionary diversity. The SIRH family alias derives from the resemblance of the genes to the sushi-ichi-related retrotransposon, but the genes are derived from an extinct retrovirus. The human genes were identified from a search for GAG homologs in the human genome. Mammalian-specific transposon transcripts Mart gene family RTL SIRH family genes SIRH/RTL family Sushi groups of Ty3/Gypsy LTR (long terminal repeat) retrotransposon-derived Sushi-class retrotransposon-derived genes retroviral-capsid-related Sushi family Retrotransposon Gag like family RTL Olfactory receptors expressed in the cell membranes of olfactory receptor neurons are responsible for the detection of odor molecules. Activated olfactory receptors are the initial player in a signal transduction cascade which ultimately produces a nerve impulse which is transmitted to the brain. These receptors are members of the class A rhodopsin-like family of G protein-coupled receptors (GPCRs). The olfactory receptors form a multigene family consisting of around 800 genes in humans and 1400 genes in mice. OR Olfactory receptors OR Immunoglobulin superfamily CAMs ( IgSF CAMs ) are a class of cell adhesion molecules. They are either homophilic or heterophilic and bind integrins or different IgSF CAMs. IgCAM IgSF CAM Immunoglobulin superfamily cell adhesion molecules Immunoglobulin-like cell adhesion molecules Ig-like cell adhesion molecule family Genome searches with dedicated sequence profiles for capsid Gag domains identified human gag-like genes, which can be classified into five distinct families on the basis of their sequence similarity to Gag proteins from different retrotransposon families. Domesticated Gag proteins Gag-like human proteins Gag like LTR retrotransposon derived genes Intact envelope genes have been shown to be transcribed in several healthy tissues, and the conservation in an otherwise degenerated ERV locus has led to speculations about a likely beneficial role for the host. These include (i) protecting the fetus due to immunomodulatory properties via an immunosuppressive domain located in the TM subunit of the envelope, (ii) preventing present-day retroviral infections by inhibiting cell entry of related exogenous retroviruses that use a common surface receptor, a process called receptor interference in which the receptor-binding-domain of SU blocks the receptor, or (iii) being used as triggers to provide cell-cell fusion in which the fusion machinery of TM is activated by binding of SU to a cellular receptor. Domesticated Env genes ERV envelope genes Env like ERV derived genes Envelope endogenous retrovirus derived genes Retroviral envelope genes Envelope ERV derived genes Glycoside hydrolase family 31 CAR subgroup CTX family IgCAM CXADR-related subfamily DNA transposable element derived genes DNA transposon derived genes Transposable elements (TEs) can give rise to new functional host genes, a process known as molecular domestication. In the human genome, more than hundred protein-coding genes are thought to be derived from TEs, representing about 0.5% of the complete set of human protein-coding genes. Transposon derived genes Transposable element derived genes HDGF family hepatoma derived growth factor family Heparin binding growth factor family N6-methyladenosine modification in mRNA influences mRNA splicing, export, localization, translation, and stability. The m6A writer complex is located in the nuclear speckle, and catalyses the transfer of methyl groups from S-adenosylmethionine (SAM) to the specific adenines on the target RNAs. METTL3 and METTL14 are the catalytic subunits in this complex. METTL3-METTL14 methyltransferase complex RNA methyltransferase complex WMM complex m6A writer complex m6A methyltransferase complex WTAP complex ROCO Roc and COR domain containing Roc/COR ROCO family ROCO GARPII complex Endosome-associated recycling protein (EARP) complex Golgi associated retrograde protein (GARP) complex This family consists of the G protein alpha subunit, which acts as a weak GTPase. G protein classes are defined based on the sequence and function of their alpha subunits, which in mammals fall into several sub-types: G(S)alpha, G(Q)alpha, G(I)alpha, transducin and G(12)alpha; there are also fungal and plant classes of alpha subunits. The alpha subunit consists of two domains: a GTP-binding domain and a helical insertion domain ( INTERPRO ). The GTP-binding domain is homologous to Ras-like small GTPases, and includes switch regions I and II, which change conformation during activation. The switch regions are loops of alpha-helices with conformations sensitive to guanine nucleotides. The helical insertion domain is inserted into the GTP-binding domain before switch region I and is unique to heterotrimeric G proteins. This helical insertion domain functions to sequester the guanine nucleotide at the interface with the GTP-binding domain and must be displaced to enable nucleotide dissociation. G alpha subunits G protein alpha subunits G-protein alpha subunits GNA Guanine nucleotide binding proteins alpha G protein subunits alpha GNA This family consists of the G protein alpha subunit group S (stimulatory) which transduces signals from various cell surface receptors to the cAMP-generating enzyme adenylyl cyclase. The G alpha-S subunit is encoded by GNAS, a complex imprinted gene that uses multiple promoters to generate several gene products. G alpha stimulatory subunits G(S)alpha subunits G-protein alpha subunits, group S GalphaS subunits Gs alpha subunits Gs proteins G protein subunits alpha, group s This family consists of the G protein alpha-Q subunit, which includes both G alpha-Q and G alpha-11. G alpha-Q proteins are widely expressed, toxin-insensitive proteins that couple various receptors to the effector enzyme phospholipase C (PLC), causing the release of calcium from internal stores via calcium channel activation. G(Q)alpha subunits G-protein alpha subunits, group Q Galphaq subunits Gq alpha subunits Gq proteins Gq/11 subunits G protein subunits alpha, group q This family consists of the G protein alpha subunit group I (inhibitory), which includes G alpha-I, G alpha-O, G alpha-T and G alpha-Z. G alpha-I proteins were originally identified by their receptor-mediated inhibition of the cAMP-generating enzyme adenylyl cyclase. G inhibitory subunits G(I)alpha subunits G-protein alpha subunits, group I GNAI Galphai subunits Galphai/o subunits Gi alpha subunits Gi proteins G protein subunits alpha, group i GNAI This family consists of the alpha-12 group of G proteins, which includes both alpha-12 group of G proteins and alpha-13 group of G proteins. G alpha-12 and G alpha-13 are ubiquitously expressed and can induce many cellular responses, including phospholipase C-epsilon activation, phospholipase D activation, cytoskeletal change, oncogenic response, apoptosis, MAP kinase activation and Na/H-exchange activation G(12)alpha subunits G-protein alpha subunit, group 12/13 G12/13 subunits G protein subunits alpha, group 12/13 Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha, beta and gamma. This entry consists of the G protein beta subunit, which assumes a barrel-shaped beta-propeller structure containing WD-40 repeats preceded by an N-terminal alpha helix. The beta subunit forms a stable dimer with the gamma subunit. The alpha subunit only contacts the beta subunit in the dimer, lying on the opposite face from the gamma subunit. G(I)/G(S)/G(T) subunits beta GNB guanine nucleotide-binding protein G(I)/G(S)/G(T) subunits beta G protein subunits beta GNB 'G protein' usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the 'large' G proteins (as opposed to the subclass of smaller, monomeric small GTPases). These proteins are activated by G protein-coupled receptors and are made up of alpha, beta and gamma subunits, the latter two referred to as the beta-gamma complex G-proteins Guanosine nucleotide-binding proteins Large G proteins Heterotrimeric G proteins Guanine nucleotide binding proteins (G proteins) are membrane-associated, heterotrimeric proteins composed of three subunits: alpha, beta and gamma. The specific combination of subunits in heterotrimeric G proteins affects not only which receptor it can bind to, but also which downstream target is affected, providing the means to target specific physiological processes in response to specific external stimuli. G proteins carry lipid modifications on one or more of their subunits to target them to the plasma membrane and to contribute to protein interactions. This entry represents the G protein gamma subunit. G protein gamma subunits G(I)/G(S)/G(O) gamma subunits GNG guanine nucleotide binding proteins gamma G protein subunits gamma GNG ARPs Actin related proteins These genes encode zinc dependent metallopeptidases in which two of the zinc ligands are histidines in a 'HEXXH' motif. The M1 family contains exopeptidases that act at the free N-terminus of polypeptides. M1 metallopeptidases These genes encode zinc dependent metallopeptidases in which two of the zinc ligands are histidines in a 'HEXXH' motif. This family includes intracellular oligopeptidases. M3 metallopeptidase family These genes encode zinc dependent metallopeptidases in which two of the zinc ligands are histidines in a 'HEXXH' motif. Neprilysins M13 metallopeptidases These genes encode zinc dependent metallopeptidases in which two of the zinc ligands are histidines in a 'HXXEH' motif. M16 metallopeptidases The exopeptidases in this family require cocatalytic ions of cobalt or manganese. M24 metallopeptidase family These genes encode zinc dependent metallopeptidases that require cocatalytic metal ions. M20 metallopeptidases These genes encode zinc dependent metallopeptidases that require cocatalytic metal ions. This family contains both aminopeptidases and carboxypeptidases. M28 metallopeptidases These genes encode zinc dependent metallopeptidases that require cocatalytic metal ions. M19 metallopeptidases M38 metallopeptidases HYAL Hyaluronidases HYAL Cleavage stimulatory factor or cleavage stimulation factor (CstF or CStF) is a heterotrimeric protein, made up of the proteins CSTF1 (55 kDa ), CSTF2 (64kDa) and CSTF3 (77kDa), totalling about 200 kDa. It is involved in the cleavage of the 3' signaling region from a newly synthesized pre- messenger RNA (mRNA) molecule. CstF is recruited by cleavage and polyadenylation specificity factor (CPSF) and assembles into a protein complex on the 3' end to promote the synthesis of a functional polyadenine tail, which results in a mature mRNA molecule ready to be exported from the cell nucleus to the cytosol for translation. The amount of CstF in a cell is dependent on the phase of the cell cycle, increasing significantly during the transition from G0 phase to S phase in mouse fibroblast and human splenic B cells. CSTF Cleavage stimulation factor subunits CSTF CPSF defines the specificity of pre-mRNA 3′ processing by recognizing the PAS. CPSF also plays important roles in transcription coupling, as it is recruited to the transcription initiation complex and accompanies RNAP II throughout the transcription process. CPSF Cleavage and polyadenylation specific factor subunits Kleisins Condensin I subunits Condensin II subunits Condensin subunits Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including algae, bacteria, higher plants, and animals. In humans, it acts as a buffer against iron deficiency and iron overload. Ferritin is found in most tissues as a cytosolic protein, but small amounts are secreted into the serum where it functions as an iron carrier. Plasma ferritin is also an indirect marker of the total amount of iron stored in the body, hence serum ferritin is used as a diagnostic test for iron-deficiency anemia. Ferritin is a globular protein complex consisting of 24 protein subunits forming a nanocage with multiple metalâ€'protein interactions. It is the primary intracellular iron-storage protein in both prokaryotes and eukaryotes, keeping iron in a soluble and non-toxic form. Ferritin that is not combined with iron is called apoferritin. Ferritin subunits Ferritins Ferritin chains Tec family tyrosine kinases Non-receptor tyrosine kinases (nRTKs) are cytoplasmic enzymes that are responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell. Unlike the receptor tyrosine kinases (RTKs), the second subgroup of tyrosine kinases, the non-receptor tyrosine kinases are cytoplasmic enzymes. Thirty-two non-receptor tyrosine kinases have been identified in human cells ( EC 2.7.10.2 ). Non-receptor tyrosine kinases regulate cell growth, proliferation, differentiation, adhesion, migration and apoptosis, and they are critical components in the regulation of the immune system. Non-receptor tyrosine kinases JAK Janus kinases Jak family tyrosine kinases JAK Csk family tyrosine kinases Fer family tyrosine kinases Fes family tyrosine kinases ABL Abelson kinases Abl family tyrosine kinases ABL Syk family tyrosine kinases NXN Nucleoredoxin family NXN GLRX Glutaredoxin domain containing GLRX MAPEG MGST membrane-associated proteins in eicosanoid and glutathione Microsomal glutathione S-transferases MGST OR1 Olfactory receptors, family 1 OR1 Glutathione S -transferases ( GSTs ), previously known as ligandins, comprise a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification. The GST family consists of three superfamilies: the cytosolic, mitochondrial, and microsomal — also known as MAPEG — proteins. Members of the GST superfamily are extremely diverse in amino acid sequence, and a large fraction of the sequences deposited in public databases are of unknown function. The Enzyme Function Initiative (EFI) is using GSTs as a model superfamily to identify new GST functions. GSTs can constitute up to 10% of cytosolic protein in some mammalian organs. GSTs catalyse the conjugation of GSH — via a sulfhydryl group — to electrophilic centers on a wide variety of substrates in order to make the compounds more water-soluble. This activity detoxifies endogenous compounds such as peroxidised lipids and enables the breakdown of xenobiotics. GSTs may also bind toxins and function as transport proteins, which gave rise to the early term for GSTs, ligandin. Glutathione S-transferases 4JC Tetraspan junctional complex superfamily CLRN Clarins CLRN TVP Tetraspan vesicle membrane proteins Gyrins SYNGR Synaptogyrins SYNGR Physins SYP Synaptophysins SYP Glucose deprivation reduces rRNA synthesis. An energy-dependent change in the NAD+/NADH ratio regulates the eNoSC complex, allowing it to couple the changing energy status with the level of rRNA transcription by regulating the epigenetic status of rRNA clusters. eNoSC promotes the restoration of energy balance and protects cells from energy deprivation-induced apoptosis. energy dependent nucleolar silencing complex eNoSC complex These genes encode ion channel proteins that are regulated by membrane voltage and extracellular Ca2+ concentration. A CALHM1 channel is a hexamer of CALHM1 monomers. CALHM genes are expressed in primate taste buds, exclusively in type II cells. CALHM Calcium homeostasis modulators CALHM Male specific lethal complex hMSL MSL histone acetyltransferase complex non-specific lethal complex NSL histone acetyltransferase complex U three protein complex A UTPa SSU processome subcomplex t-Utp UTPa subcomplex The small subunit (SSU) processome is a large ribonucleoprotein (RNP) in eukaryotes required for the assembly of the SSU of the ribosome as well as for the maturation of the 18S rRNA. Small subunit processome SSU processome U3 snoRNP U3 small nucleolar ribonucleoprotein MPHOSPH10 subcomplex MPP10 complex MPP10 subcomplex CLEC18 Mannose receptor like CAP and C-type lectin domain containing CLEC18 LHFPL lipoma HMGIC fusion partner like LHFPL tetraspan proteins LHFPL OR2 Olfactory receptors, family 2 OR2 UTPc subcomplex CFAP Cilia and flagella associated CFAP ARM-like ARMH Armadillo-like helical superfamily Armadillo like helical domain containing ARMH IPR002553 Clathrin/coatomer adaptor, adaptin-like, N-terminal domain containing PUM Pumilio homology domain containing PUM TOG domain containing TSC1-TSC2 complex TSC complex NineTeen Complex associated proteins NTC associated proteins The U1 snRNP complex is involved in pre-mRNA splicing events, playing an integral part in splice-site selection and spliceosome assembly. U1 snRNP may also regulate transcript length and the directionality of transcription via competition with components of the polyadenylation machinery. U1 snRNP U1 small nuclear ribonucleoprotein OR3 Olfactory receptors, family 3 OR3 The SMN complex is essential for the biogenesis of spliceosomal snRNP particles, which are required for splicing of nuclear pre-mRNAs. Through its binding to specific sequences in the snRNAs, the SMN complex surveys the correct identity of the target RNAs and facilitates snRNP assembly. Survival of motor neuron complex SMN complex The U2 snRNP complex is involved in pre-mRNA splicing events. U2 snRNP plays a role in the recognition of the 3 prime splice site and the branch site in introns. 17S U2 snRNP U2 snRNP U2 small nuclear ribonucleoprotein In order for U6 snRNA to enter into functional spliceosomes, it must first interact with U4 snRNA through an extensive base-pair interaction in a di-snRNP. Of the five snRNAs, U6 is the most likely to play a direct role in catalysis since it associates with the 5′ splice site of the pre-mRNA in the active core of functional spliceosomes (PMID:20659011) U4/U6 snRNP U4/U6 small nuclear ribonucleoprotein particle The U5 snRNP complex is involved in pre-mRNA splicing events. Of the six U5 snRNP-specific proteins, three are NTPases. DDX23 and SNRNP200 are members of the DEXD/H box family and EFTUD2 is the sole GTPase identified in the spliceosome to date. The NTPases of the U5 snRNP are involved in the critical switch in which U1 is replaced by U6 at the 5 prime splice site. U5 snRNP U5 small nuclear ribonucleoprotein The spliceosomal A complex is an intermediate complex in the assembly of a spliceosome. The entry of the U2 snRNP to the <a href='https://www.genenames.org/data/genegroup/#!/group/1522'>E complex</a> defines the branch-point and leads to the formation of the A complex. The A complex associates with the <a href='https://www.genenames.org/data/genegroup/#!/group/1506'>U4/U6.U5 tri-snRNP</a> to generate the <a href='https://www.genenames.org/data/genegroup/#!/group/1507'>B complex</a>. PS complex prespliceosome complex Spliceosomal A complex LSM like Sm proteins LSm proteins LSM The U4/U6.U5 triple complex is the largest intermediate subcomplex on the assembly pathway for the human spliceosome. U4/U6.U5 tri-snRNP tri-snRP complex The spliceosomal B complex is an intermediate complex in the assembly of a spliceosome. The <a href='/data/genegroup/#!/group/1504' target='_blank'>spliceosomal A complex</a> associates with the U4/U6.U5 tri-snRNP to generate the B complex. The B complex remains catalytically inactive until it undergoes extensive compositional and conformational rearrangements, including the dissociation of U1 and U4, resulting in the formation of the <a href='https://www.genenames.org/data/genegroup/#!/group/1508'>Bact complex</a>. This is converted into a catalytically active spliceosome (designated B*) by the action of the RNA helicase DHX16. The B* complex catalyses the first step of splicing, generating the cleaved 5' exon and intron-3' exon lariat intermediates and forming the <a href='https://www.genenames.org/data/genegroup/#!/group/1510'>C complex</a>. pre-catalytic spliceosome Spliceosomal B complex Although all snRNPs are present in the <a href=''>B complex</a>, it is still catalytically inactive and requires major conformational and compositional rearrangements (i.e., activation) in order to become competent to facilitate the first transesterification step of splicing. During spliceosome activation U1 and U4 are destabilized or released, giving rise to the activated spliceosome (i.e., the Bact complex). Subsequently, after a structural rearrangement is catalyzed by the DExH/D-box protein Prp2, the catalytically activated spliceosome (B* complex) is formed. The B* complex catalyses the first step of splicing, generating the cleaved 5' exon and intron-3' exon lariat intermediates, and at this stage the <a href=''>spliceosomal C complex</a> is generated. Spliceosomal B activated complex complex B* Spliceosomal Bact complex OR4 Olfactory receptors, family 4 OR4 After additional RNP rearrangements, the C complex catalyses the second step of splicing, resulting in the ligation of the 5' and 3' exons and release of the intron in the form of a lariat. catalytic spliceosome Spliceosomal C complex Voltage-dependent calcium channels ( VDCCs ) are a group of voltage-gated ion channels found in the membrane of excitable cells ( e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca 2+. These channels are slightly permeable to sodium ions, so they are also called Ca 2+ -Na + channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VDCCs are normally closed. They are activated ( i.e., opened) at depolarized membrane potentials and this is the source of the 'voltage-dependent' epithet. The concentration of calcium (Ca 2+ ions) is normally several thousand times higher outside of the cell than inside. Activation of particular VDCCs allows Ca 2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. VDCCs have been immunolocalized in the zona glomerulosa of normal and hyperplastic human adrenal, as well as in aldosterone -producing adenomas (APA), and in the latter T-type VDCCs correlated with plasma aldosterone levels of patients. Excessive activation of VDCCs is a major component of excitotoxicity, as severely elevated levels of intracellular calcium activates enzymes which, at high enough levels, can degrade essential cellular structures. CACNG CCAγ Calcium channel gamma subunit Calcium channel auxiliary gamma subunits CACNG Voltage-dependent calcium channels ( VDCCs ) are a group of voltage-gated ion channels found in the membrane of excitable cells ( e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca 2+. These channels are slightly permeable to sodium ions, so they are also called Ca 2+ -Na + channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VDCCs are normally closed. They are activated ( i.e., opened) at depolarized membrane potentials and this is the source of the 'voltage-dependent' epithet. The concentration of calcium (Ca 2+ ions) is normally several thousand times higher outside of the cell than inside. Activation of particular VDCCs allows Ca 2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. VDCCs have been immunolocalized in the zona glomerulosa of normal and hyperplastic human adrenal, as well as in aldosterone -producing adenomas (APA), and in the latter T-type VDCCs correlated with plasma aldosterone levels of patients. Excessive activation of VDCCs is a major component of excitotoxicity, as severely elevated levels of intracellular calcium activates enzymes which, at high enough levels, can degrade essential cellular structures. CACNA1 Calcium voltage-gated channel alpha1 subunits CACNA1 Voltage-dependent calcium channels ( VDCCs ) are a group of voltage-gated ion channels found in the membrane of excitable cells ( e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca 2+. These channels are slightly permeable to sodium ions, so they are also called Ca 2+ -Na + channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VDCCs are normally closed. They are activated ( i.e., opened) at depolarized membrane potentials and this is the source of the 'voltage-dependent' epithet. The concentration of calcium (Ca 2+ ions) is normally several thousand times higher outside of the cell than inside. Activation of particular VDCCs allows Ca 2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. VDCCs have been immunolocalized in the zona glomerulosa of normal and hyperplastic human adrenal, as well as in aldosterone -producing adenomas (APA), and in the latter T-type VDCCs correlated with plasma aldosterone levels of patients. Excessive activation of VDCCs is a major component of excitotoxicity, as severely elevated levels of intracellular calcium activates enzymes which, at high enough levels, can degrade essential cellular structures. CACNA2D Calcium voltage-gated channel auxiliary alpha2delta subunits CACNA2D Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+-Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VGCCs are normally closed. They are activated (i.e., opened) at depolarized membrane potentials and this is the source of the 'voltage-gated' epithet. The concentration of calcium (Ca2+ ions) is normally several thousand times higher outside the cell than inside. Activation of particular VGCCs allows a Ca2+ influx into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. VGCCs have been immunolocalized in the zona glomerulosa of normal and hyperplastic human adrenal, as well as in aldosterone-producing adenomas (APA), and in the latter T-type VGCCs correlated with plasma aldosterone levels of patients. Excessive activation of VGCCs is a major component of excitotoxicity, as severely elevated levels of intracellular calcium activates enzymes which, at high enough levels, can degrade essential cellular structures. CACNB Calcium voltage-gated channel auxiliary beta subunits CACNB The spliceosomal P complex is a large stable splicing complex that forms after the spliceosomal <a href='https://www.genenames.org/data/genegroup/#!/group/1510'>C complex</a> but before mRNA release. post-catalytic complex post-spliceosomal complex Spliceosomal P complex SF3b is a multi-protein complex which recognizes the branch point adenosine of pre-mRNA as part of a larger U2 snRNP or U11/U12 di-snRNP in the dynamic spliceosome machinery. PHF5A-SF3b complex SF3b complex A spliceosome is a large and complex molecular machine found primarily within the splicing speckles of the cell nucleus of eukaryotic cells. The spliceosome is assembled from snRNAs and protein complexes. The spliceosome removes introns from a transcribed pre-mRNA, a type of primary transcript. This process is generally referred to as splicing. U2 dependent spliceosome Major spliceosome OR5 Olfactory receptors, family 5 OR5 U12-type introns are a minor subgroup of introns, distinct from the major or U2-type introns. U12-type introns are present in most eukaryotes but only account for less than 0.5% of all introns in any given genome. They are processed by a specific U12-dependent spliceosome, which is similar to, but distinct from, the major spliceosome. The U11, U12 and U4atac/U6atac snRNPs are functional analogs of the U1, U2 and U4/U6 snRNPs in the <a href='https://www.genenames.org/data/genegroup/#!/group/1518'>major spliceosome</a>. U12-dependent spliceosome Minor spliceosome The U11/U12 di-snRNP forms part of the <a href='https://www.genenames.org/data/genegroup/#!/group/1520'>minor spliceosome complex</a>. U11 and U12 snRNPs bind U12-type pre-mRNAs as a preformed di-snRNP complex, simultaneously recognizing the 5' splice site and branchpoint sequence. Thus, within the U12-type prespliceosome, U11/U12 components form a molecular bridge connecting both ends of the intron. 18S U11/U12 snRNP U11/U12 small nuclear ribonucleoprotein U11/U12 di-snRNP The assembly of the spliceosome occurs in a stepwise manner. First, U1 snRNP is bound to the 5′SS of the pre-mRNA together with various proteins generating complex E. The SF1 encoded protein recognizes the branch point sequence (BPS) at the 3' splice site during the formation of early complex E thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. U2AF2 interacts with SF1 and recruits the U2 snRNP to the spliceosome. The entry of the U2 snRNP defines the branch-point and leads to the formation of the <a href='https://www.genenames.org/data/genegroup/#!/group/1504'>A complex</a>. early complex E spliceosomal commitment complex Spliceosomal E complex These 45S pre-ribosomal RNA genes, and the 18S, 28S and 5.8S rRNA which may be processed from each 45S rRNA shown below, are found outside of the 13p12, 14p12, 15p12, 21p12 and 22p12 rRNA clusters that are the sites of rRNA transcription in the nucleolus. Therefore it is not certain whether these genes would be transcribed into functional rRNA molecules. To denote this, each gene symbol has the letter 'N' before its numerical identifier. rRNA orphons Ribosomal 45S rRNA genes outside of clusters GSDM Gasdermins GSDM OR6 Olfactory receptors, family 6 OR6 The Vps-C complexes CORVET (class C core vacuole/endosome tethering) and HOPS (homotypic fusion and protein sorting) are found on endosomes and lysosomes, where they control membrane trafficking pathways. VPS-C complexes The HOPS tethering complex regulates late-endosomal tethering and shares several subunits with the CORVET complex that regulates early endosomal tethering. The membrane-targeting module in HOPS binds RILP (Rab interacting lysosomal protein). VPS11 acts as a molecular switch that binds either the CORVET complex specific TGFBRAP1 or HOPS specific VPS39/RILP thereby allowing selective targeting of these tethering complexes to early- or late endosomes to time fusion events in the endo/lysosomal pathway. VPS homotypic fusion and protein sorting complex HOPS complex VPS The CORVET tethering complex regulates early-endosomal tethering and shares several subunits with the HOPS complex that regulates late endosomal tethering. VPS11 acts as a molecular switch that binds either the CORVET complex specific TGFBRAP1, or HOPS specific VPS39/RILP thereby allowing selective targeting of these tethering complexes to early- or late endosomes to time fusion events in the endo/lysosomal pathway. class C core vacuole/endosome tethering complex CORVET complex Metazoans have two RNase P enzymes: a nuclear RNA-based RNase P and a mitochondrial PRORP (protein-only RNase P). Human mitochondrial RNase P consists of three subunits and lacks an RNA component. RNase P enzymes are metal ion-dependent endonucleases: hydrolases that catalyze site-specific phosphodiester bond hydrolysis primarily within pre-tRNA. mitochondrial PRORP mt-RNase P complex protein only RNase P proteinaceous RNase P Mitochondrial RNase P complex The B9 domain-containing proteins are found only in organisms that form cilia and all B9 proteins are involved in ciliary functions in both C. elegans and vertebrates. B9 family B9-C2 domain containing B9 domain containing Zizimin proteins belong to the Dock (Dedicator of Cytokinesis) superfamily of Guanine nucleotide Exchange Factor (GEF) proteins. This family of proteins plays a role in the regulation of Rho family small GTPases. Together the Rho family of small GTPases and the Dock/Zizimin proteins play a vital role in a number of cell processes including cell migration, apoptosis, cell division and cell adhesion. C2 domain containing DOCK and Zizimin proteins DOCK DOCK C2 domain containing DOCK family Rho guanine nucleotide exchange factors DOCK family Rho GEFs DOCK The NT-C2 domain is found in several microfilament/actin and endocytosis related proteins. NT-C2 domain containing FASTK FASTK mitochondrial RNA binding family FASTK p120ctn p120 catenin family OR7 Olfactory receptors, family 7 OR7 Catenins PKP Plakophilins PKP CTNNB Beta catenins CTNNB CTNNA Alpha catenins CTNNA Delta catenins MKS module Meckel syndrome complex MKS complex Nephronophthisis complex NPHP complex Mitochondrial pyruvate dehydrogenase complex PDH Pyruvate dehydrogenase complex PDH The TCF/LEF family is a group of transcription factors which bind to DNA through a high mobility group domain. They are involved in the Wnt signaling pathway, where they recruit the coactivator beta-catenin to enhancer elements of genes they target. They can also recruit members of the Groucho family of corepressors. TCF/LEF family TCF/LEF transcription factor family OR8 Olfactory receptors, family 8 OR8 Tim17 and Tim23 form the core of the complex onto which all other subunits assemble. Complete translocation into the matrix is mediated by the import motor of the TIM23 complex, also referred to as PAM (presequence translocase-associated motor). mtHsp70 (encoded by HSPA1A, HSPA1B and HSPA1L,) is the central component of the import motor. Its ATP-dependent action, regulated by the J and J-like proteins DNAJC19 (aliases: Tim14/Pam18) and Tim16/Pam16 and the nucleotide exchange factor GRPEL1 (yeast ortholog Mge1), drives translocation of proteins across the inner membrane. TIM23 complex TIMM complex translocase of inner mitochondrial membrane complex TIM23 complex SF3A SF3a complex SF3A Retriever complex COMMD/CCDC22/CCDC93 complex CCC complex SET1-family enzymes are only fully active in the context of a multi-subunit complex, which includes a protein module comprised of WDR5, RbBP5, ASH2L and DPY-30 (WRAD). These proteins bind in close proximity to the catalytic SET domain of SET1-family enzymes and stimulate H3K4 methyltransferase activity. The mechanism by which WRAD promotes catalysis involves elements of allosteric control and possibly the utilization of a second H3K4 methyltransferase active site present within WRAD itself. WRAD components also engage in physical interactions that recruit SET1-family proteins to target sites on chromatin. WRAD complex Ski2 like RNA helicases OR9 Olfactory receptors, family 9 OR9 The C-terminal to LisH (CTLH) complex (called the glucose-induced degradation deficient (GID) complex in yeast), is a multi-subunit E3 ligase complex highly conserved from Saccharomyces cerevisiae to humans, with roles in fundamental pathways controlling homeostasis and development in several species. The CTLH complex is characterized by its RING heterodimer, multiple protein interaction domains, and LisH, CTLH, and CRA motifs present on most protein subunits. In humans, RANBP9 (homolog of Gid1), GID8 and ARMC8 (similar to Gid5) act as a scaffold; RMND5A (homolog of Gid2) and MAEA (homolog of Gid9) are the RING heterodimers required for E3 ligase activity; and GID4 (homolog of Gid4) acts a substrate receptor (WDR26, homologue of Gid7, may also act in this role). WDR26 and/or MKLN1 bind RANBP9 and facilitate oligomerization of the complex. Additionally, paralogues of RMND5A and RANBP9, RMND5B and RANBP10 have been implied as human complex members so are included here. Human YPEL5 and its orthologs (Moh1 in yeast) are also part of the complex, but their role is unclear. Key to the activity of the complex, RMND5A/Gid2 and MAEA/Gid9 provide a unique RING domain heterodimer that can bind the E2 enzyme UBE2H (Ubc8 in S. cerevisiae) and stimulate E2-catalyzed Ub transfer to a recruited substrate. C-terminal to LisH complex GID GID complex MRCTLH complex Muskelin/RanBP9/CTLH complex CTLH complex subunits GID novel SH2-containing proteins NSP adaptor proteins WBP1/VOPP1 family PROPPIN family WD-repeat protein interacting with phosphoinositides family WIPI WIPI family WIPI Purinosome OR10 Olfactory receptors, family 10 OR10 NDC80 kinetochore complex KNL1, MIS12, NDC80 network KMN network KNL1 complex CCAN Constitutive centromere associated network DAZ DAZ RNA binding protein family DAZ WWC WWC family WWC Neurexin (NRXN) is a presynaptic protein that helps to connect neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular domain interacts with proteins in the synaptic cleft, most notably neuroligin, while the intracellular cytoplasmic portion interacts with proteins associated with exocytosis. Neurexin and neuroligin 'shake hands,' resulting in the connection between the two neurons and the production of a synapse. Neurexins mediate signaling across the synapse, and influence the properties of neural networks by synapse specificity. Neurexins were discovered as receptors for α-latrotoxin, a vertebrate-specific toxin in black widow spider venom that binds to presynaptic receptors and induces massive neurotransmitter release. In humans, alterations in genes encoding neurexins are implicated in autism and other cognitive diseases, such as Tourette syndrome and schizophrenia. NRXN Neurexins NRXN Neuroligin (NLGN), a type I membrane protein, is a cell adhesion protein on the postsynaptic membrane that mediates the formation and maintenance of synapses between neurons. Neuroligins act as ligands for β-Neurexins, which are cell adhesion proteins located presynaptically. Neuroligin and β-neurexin 'shake hands,' resulting in the connection between two neurons and the production of a synapse. Neuroligins also affect the properties of neural networks by specifying synaptic functions, and they mediate signalling by recruiting and stabilizing key synaptic components. Neuroligins interact with other postsynaptic proteins to localize neurotransmitter receptors and channels in the postsynaptic density as the cell matures. Additionally, neuroligins are expressed in human peripheral tissues and have been found to play a role in angiogenesis. In humans, alterations in genes encoding neuroligins are implicated in autism and other cognitive disorders. NRLGN Neuroligins NRLGN There are five MYST histone acetyltransferases in mammals. They are defined by their MYST histone acetyltransferase catalytic domain. This domain contains an acetyl-coenzyme A binding domain and an unusual C2HC-type zinc finger. KAT MYST type domain containing lysine acetyltransferases KAT NTF Neurotrophins NTF GFL GFLs GDNF family ligands The repulsive guidance molecule (RGM) family function as co-receptors that enhance cellular responses to BMP ligands. RGM family members are differentially expressed in a wide range of tissues, and have been suggested to have diverse biologic roles ranging from repulsive axonal guidance, neural tube closure, neuronal differentiation, cell survival, axonal regeneration after injury, immunity, inflammation, and iron homeostasis regulation. RGM family Repulsive guidance molecule family The first step in PM phosphoinositide synthesis is the conversion of phosphatidylinositol (PI) to PI4P, the precursor of PI(4,5)P2 and PI(3,4,5)P3 This conversion is catalyzed by the PI4KIIIα complex. PI4KIIIalpha complex PI4KIIIα complex PI4KA lipid kinase complex OR11 Olfactory receptors, family 11 OR11 The Beclin1–class III phosphatidylinositol 3-kinase (PI3KC3) complex produces an autophagy-specific pool of phosphatidylinositol 3-phosphate (PI3P). Inhibition of the activity or loss of the lipid kinase components inhibits autophagy. BECN1 interacts with a number of proteins, forming multiple functionally distinct complexes, and this allows Beclin1 to respond to different signals regulating autophagy. Beclin 1-Vps34 complex Beclin1-PI3KC3 complex PIK3C3 complex subunits Interferon inducible transmembrane proteins have diverse roles, including the control of cell proliferation, promotion of homotypic cell adhesion, protection against viral infection, promotion of bone matrix maturation and mineralisation, and mediating germ cell development. IFITM IFITM family Interferon induced transmembrane protein family IFITM Cadherins are calcium-dependent transmembrane proteins that generally mediate cell-cell adhesion or cell-cell recognition and are characterized by the presence of at least two consecutive extracellular cadherin-specific motifs, called cadherin repeats, with conserved calcium-binding amino acid residues. Calcium-dependent adhesion proteins Cadherins OR12 Olfactory receptors, family 12 OR12 This is a family of transmembrane proteins with a common two TM structure. CD225 family Interferon induced transmembrane protein domain containing Dispanins Junctophilins (JPHs) are members of a junctional membrane complex protein family important for the physical approximation of plasmalemmal and sarcoplasmic/endoplasmic reticulum membranes. As such, JPHs facilitate signal transduction in excitable cells between plasmalemmal voltage-gated calcium channels and intracellular calcium release channels. JPH Junctophilins JPH Marilins mediate interactions between macromolecular components of the extracellular matrix, e.g., collagens and proteoglycans. They are composed of von Willebrand factor type A and epidermal growth factor-like domains and the subunits oligomerize via coiled-coil domains. MATN Matrilins MATN 2-phosphoglycerate dehydratase ENO Phosphopyruvate hydratase Enolases ENO BAF-type SWI/SNF complex subunits BRG1-Associated Factor complex SWI/SNF complex SWI/SNF-alpha complex SWItch/Sucrose Non-Fermenting complex cBAF complex canonical BAF complex mSWI/SNF complex BAF complex subunits Polybromo-Associated BAF complex SWI/SNF-beta complex PBAF complex subunits ncBAF complex non-canonical BAF complex GBAF complex subunits Calsarcins FATZ family MYOZ Myozenins MYOZ PTF1 bHLH complex PTF1 complex MYF Myogenic regulatory family MYF Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na +, K +, Ca 2+, or Cl - to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand ), such as a neurotransmitter. These proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an allosteric binding site). This modularity has enabled a 'divide and conquer' approach to finding the structure of the proteins (crystallising each domain separately). The function of such receptors located at synapses is to convert the chemical signal of presynaptically released neurotransmitter directly and very quickly into a postsynaptic electrical signal. Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential. LGICs are classified into three superfamilies which lack evolutionary relationship: Cys-loop receptors, Ionotropic glutamate receptors and ATP-gated channels. LGICs Ligand-gated ion channels Ligand gated ion channels The CPLANE multiprotein complex is essential for the assembly of IFT-A particles and intraflagellar transport. CPLANE Ciliogenesis and planar polarity effector complex subunits CPLANE The metallo-β-lactamase (MBL) superfamily constitutes a group of proteins found in all domains of life that share a characteristic αββα fold with the ability to bind transition metal ions. Such metal binding sites may have divalent transition metal ions like Zn(II), Fe(II)/Fe(III) and Mn(II), and are located at the bottom of a wide cleft able to accommodate diverse substrates. The name was adopted after the first members of the superfamily to be studied experimentally: a group of zinc-dependent hydrolytic enzymes conferring bacterial resistance to β-lactam antibiotics. Proteins belonging to the MBL superfamily usually combine at least one MBL domain with additional domains that provide different functions, such as substrate recognition or binding to other polypeptides, in a modular fashion. Thus, MBL superfamily members grasp the metal-assisted water-activation ability of the MBL domain in order to perform a wide variety of hydrolytic reactions. MBL domain containing family MBL fold family Metallo-beta-lactamase fold containing family MBL domain containing glyoxalase 2 subfamily MBL fold containing DNA/RNA interacting subfamily MICOS MICOS complex subunits MINOS complex subunits MitOS complex Mitofilin/Fcj1 complex subunits mitochondrial contact site complex subunits mitochondrial inner membrane organizing system subunits mitochondrial organizing structure subunits Mitochondrial contact site and cristae organizing system subunits MICOS LIM-kinases and related TESKs specifically phosphorylate cofilin at Ser-3 and thereby inhibit the actin binding, severing, and depolymerizing activities of cofilin. LIMK/TESK kinase family In eukaryotes, almost all RNA species are processed at their 3' ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. TENT Terminal nucleotidyltransferases TENT OR13 Olfactory receptors, family 13 OR13 Albuminoid family IPR022049 represents the C-terminal region of a family of FAM69 proteins from Metazoa and Viridiplantae that are active protein-kinases. The family members have a short transmembrane helix close to the N terminus, and thereafter are highly enriched with cysteines. FAM69 proteins are localised to the endoplasmic reticulum. Many members also have a short EF-hand, calcium-binding, domain just upstream of the kinase domain. The exact function of the more N-terminal family is uncertain. DIPK Divergent protein kinase domain family DIPK RAB11FIP RAB11 binding domain containing RAB11FIP SNAR small NF90-associated RNAs snaRs Small NF90 (ILF3) associated RNAs SNAR AGC family kinases MAL and related proteins for vesicle trafficking and membrane linking domain containing MARVEL domain containing This comprises a group of genes encoding cytoplasmic factors that are involved in axonemal dynein pre-assembly. DNAAF Axonemal dynein assembly factors DNAAF NRG Neuregulins NRG OR14 Olfactory receptors, family 14 OR14 calcium/calmodulin dependent protein kinases CAMK kinase families OOSP OOSP family OOSP My-T-BRC complex ATP-dependent chromatin remodeling complex required for efficient DNA replication through highly condensed chromatin. It facilitates this process by mediating the sliding of nucleosomes from an end position to the center of a 248 base pair rDNA without causing major trans displacement of histones. CHRAC CHRAC chromatin remodeling complex Chromatin accessibility complex Nua4 complex Tip60 complex p400/TIP60/NuA4 Complex Tip60/Nua4 histone acetyltransferase complex subunits GASPIDs Granule associated serine proteases of immune defence Four-jointed protein kinases family GASK Golgi associated kinase family GASK Complement system activation components Complement system regulators and receptors OR51 Olfactory receptors, family 51 OR51 C1q domain containing HEX Hexosaminidases HEX Ack family nonreceptor tyrosine kinases TNK family tyrosine kinases Fak family tyrosine kinases PTK2 family tyrosine kinases Brk family tyrosine kinases PTK6 family tyrosine kinases COE Collier/Olf1/EBF EBF Early B-cell factors EBF Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle. This is how clathrin gets its name, from the Latin clathratus meaning like a lattice. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection. Clathrin subunits α-Amylase is a protein enzyme EC 3.2.1.1 that hydrolyses alpha bonds of large, alpha-linked polysaccharides, such as starch and glycogen, yielding glucose and maltose. It is the major form of amylase found in humans and other mammals. It is also present in seeds containing starch as a food reserve, and is secreted by many fungi. AMY alpha-amylases Amylases alpha AMY Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The best-known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread of influenza infection. The viral neuraminidases are frequently used as antigenic determinants found on the surface of the influenza virus. Some variants of the influenza neuraminidase confer more virulence to the virus than others. Other homologues are found in mammalian cells, which have a range of functions. At least four mammalian sialidase homologues have been described in the human genome (see NEU1, NEU2, NEU3, NEU4). Glycoside Hydrolase Family 33 NEU Neuraminidases NEU OR52 Olfactory receptors, family 52 OR52 Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalyze the hydrolysis of glycosidic bonds in complex sugars. They are extremely common enzymes with roles in nature including degradation of biomass such as cellulose (cellulase), hemicellulose, and starch (amylase), in anti-bacterial defense strategies (e.g., lysozyme), in pathogenesis mechanisms (e.g., viral neuraminidases) and in normal cellular function (e.g., trimming mannosidases involved in N-linked glycoprotein biosynthesis). Together with glycosyltransferases, glycosidases form the major catalytic machinery for the synthesis and breakage of glycosidic bonds. Glycosidases Glycoside hydrolases Glycosyl hydrolases Glycoside hydrolase family Glycoside Hydrolase Family 79 HPSE Heparanases HPSE Glycoside hydrolase family 1 FUCA Glycoside Hydrolase Family 29 Alpha-L-fucosidases FUCA Beta galactosidases GLB Glycoside Hydrolase Family 35 Galactosidases beta GLB GLA Glycoside Hydrolase Family 27 alpha-galactosidases Galactosidases alpha GLA SHLD Shieldin complex SHLD FAM230 Family with sequence similarity 230 FAM230 Inhibitor of histone acetyl transferase complex INHAT complex SET complex OR55 Olfactory receptors, family 55 OR55 CRIM Cysteine rich transmembrane BMP regulators CRIM CHRD Chordin family CHRD Activin subunits INH Inhibin subunits INH Glutamyl-tRNA amidotransferase subunits TGF-beta TGFB Transforming growth factor beta family TGFB pseudouridylate synthases Pseudouridine synthases 2-oxo acid dehydrogenase family OGDH Oxoglutarate dehydrogenase family OGDH FMO Flavin containing monooxygenases FMO MLCK family MYLK Myosin light chain kinase family MYLK Basigin family OR56 Olfactory receptors, family 56 OR56 AP Adaptor related protein complexes AP AP1 Adaptor related protein complex 1 AP1 AP2 Adaptor related protein complex 2 AP2 AP3 Adaptor related protein complex 3 AP3 AP4 Adaptor related protein complex 4 AP4 AP5 Adaptor related protein complex 5 AP5 In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex. 7SK small nuclear ribonucleoprotein complex 7SK snRNP complex The nuclear endpoint of the Wnt/β-catenin signalling cascade is marked by the Wnt enhanceosome, a multiprotein complex. The Wnt enhanceosome enables β-catenin to gain access to target genes, to relieve their transcriptional repression by members of the TLE family. Wnt enhanceosome complex EML echinoderm microtubule associated protein like EMAP like EML Biogenic amine receptor are a variety of neurotransmitter receptors that are sensitive to biogenic amine neurotransmitters. They belong to the G protein-coupled receptor (GPCR) family of transmembrane receptors, specifically within GPCR 'Family A' ( Rhodopsin -like receptors). Biogenic amine receptors Amine receptors TLE groucho related gene family transducin like enhancer of split TLE family TLE tRNA pseudogenes Cytoplasmic transfer RNA pseudogenes MTX Metaxins MTX Mitochondrial inner membrane folds into cristae, which significantly increase its surface and are important for mitochondrial function. The stability of cristae depends on the mitochondrial contact site (MICOS) complex. In human mitochondria, the inner membrane MICOS complex interacts with the outer membrane sorting and assembly machinery (SAM) complex, to form the mitochondrial intermembrane space bridging complex (MIB). MIB complex Mitochondrial intermembrane space bridging complex Subcortical maternal complex The SAM complex is an evolutionary conserved machinery, involved in the sorting and assembly of β-barrel proteins into the outer mitochondrial membrane. SAM complex SAM/TOB complex TOB/SAM complex outer membrane sorting and assembly machinery complex Mitochondrial sorting and assembly machinery complex Endoribonucleases Long non-coding RNA genes that contain a microRNA gene in either an intron or an exon on the same strand are assigned the format [microRNA gene symbol]HG e.g. MIR22HG for 'MIR22 host gene'. MIR#HG MicroRNA non-coding host genes MIR#HG The Notch signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. Mammals possess four different notch receptors, referred to as NOTCH1, NOTCH2, NOTCH3, and NOTCH4. The notch receptor is a single-pass transmembrane receptor protein. It is a hetero-oligomer composed of a large extracellular portion, which associates in a calcium-dependent, non-covalent interaction with a smaller piece of the notch protein composed of a short extracellular region, a single transmembrane-pass, and a small intracellular region.Notch signaling promotes proliferative signaling during neurogenesis, and its activity is inhibited by Numb to promote neural differentiation. It plays a major role in the regulation of embryonic development. NOTCH Notch receptors NOTCH The adrenergic receptors (or adrenoceptors ) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). Many cells possess these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system. The sympathetic nervous system is responsible for the fight-or-flight response, which includes widening the pupils of the eye, mobilizing energy, and diverting blood flow from non-essential organs to skeletal muscle. ADR Adrenergic receptors Adrenoceptors ADR In the human genome over half of microRNA genes are hosted by other genes, either in the introns, or to a lesser extent, the exons. Such microRNA host genes can be either protein-coding or non-coding. MiRNA host genes MicroRNA host genes These protein coding genes host microRNA genes in their introns or exons. MicroRNA protein coding host genes lecithin:retinol acyltransferase like domain containing family LRAT domain containing Macro domain containing SMCR8-WDR41-C9ORF72 tripartite complex SWC tripartite complex MiR-1 family miR-1/206 family MicroRNA MIR1/206 family let-7 family let-7/miR-98 family MicroRNA MIRLET7 family miR-9 family MicroRNA MIR9 family Deoxyribonucleoside kinases 5-hydroxytryptamine (serotonin) receptors, G protein-coupled HTR serotonin receptors, G protein-coupled 5-hydroxytryptamine receptors, G protein-coupled HTR The miR-10 microRNA precursor is a short non-coding RNA gene involved in gene regulation. It is part of an RNA gene family which contains miR-10, miR-51, miR-57, miR-99 and miR-100. miR-10, miR-99 and miR-100 have now been predicted or experimentally confirmed in a wide range of species. miR-10 microRNA family MicroRNA MIR10/100 family miR-29 family MicroRNA MIR29 family mir-34/449 family MicroRNA MIR34/449 family miR-17 family MicroRNA MIR17 family miR-19 family MicroRNA MIR19 family miR-25 family miR-92 family MicroRNA MIR25/92 family MIR124 MicroRNA MIR124 family MIR124 mir-133 is a type of non-coding RNA called a microRNA that was first experimentally characterised in mice. Homologues have since been discovered in several other species including invertebrates such as the fruitfly Drosophila melanogaster. Each species often encodes multiple microRNAs with identical or similar mature sequence. For example, in the human genome there are three known miR-133 genes: miR-133a-1, miR-133a-2 and miR-133b found on chromosomes 18, 20 and 6 respectively. The mature sequence is excised from the 3' arm of the hairpin. miR-133 is expressed in muscle tissue and appears to repress the expression of non-muscle genes. MIR133 miR-133 family MicroRNA MIR133 family MIR133 The miR-8 microRNA precursor (homologous to miR-141, miR-200, miR-236), is a short non-coding RNA gene involved in gene regulation. miR-8 in Drosophila melanogaster is expressed from the 3' arm of related precursor hairpins (represented here), along with miR-200, miR-236, miR-429 and human and mouse homolog miR-141. Members of this precursor family have now been predicted or experimentally confirmed in a wide range of species. The bounds of the precursors are predicted based on conservation and base pairing and are not generally known. The miR-200 family is highly conserved in bilaterian animals, with miR-8 as the sole homolog in Drosophila. This species has accordingly been used heavily in work looking to uncover the biological function of the miR-200 family. miR-8 has been observed at all developmental stages of the embryo, and is present in cultured S2 cells of D. melanogaster. Its expression has been seen to be strongly upregulated in larvae and this expression then sustained through to adulthood. miR-8 family mir-8/mir-141/mir-200 microRNA family MicroRNA MIR141/200 family The serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptors ( GPCRs ) and ligand-gated ion channels ( LGICs ) found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, dopamine, epinephrine / norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin, cortisol, corticotropin, and substance P, among others. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens. The serotonin receptors are known to regulate longevity and behavioral aging in the nematode, Caenorhabditis elegans. 5-HT receptors 5-hydroxytryptamine (serotonin) receptors HTR serotonin receptors 5-hydroxytryptamine receptors HTR In molecular biology, the microRNA miR-219 was predicted in vertebrates by conservation between human, mouse and pufferfish and cloned in pufferfish. It was later predicted and confirmed experimentally in Drosophila. Homologs of miR-219 have since been predicted or experimentally confirmed in a wide range of species, including the platyhelminth Schmidtea mediterranea, several arthropod species and a wide range of vertebrates (MIPF0000044). The hairpin precursors (represented here) are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 5' arm of the hairpin. miR-219 has also been linked with NMDA receptor signalling in humans by targeting CaMKIIγ (a kind of protein kinase dependent to calcium and calmodulin) expression. And it has been suggested that deregulation of this miRNA can lead to the expression of mental disorders such as schizophrenia. miR-219 can also regulate Recent findings show that miR-219 is linked with Tau toxicity, suggesting that miR-219 is involved in neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease etc. MIR219 miR-219 family MicroRNA MIR219 family MIR219 miR-23 family MicroRNA MIR23 family MIR128 miR-128 family MicroRNA MIR128 family MIR128 In molecular biology, miR-130 microRNA precursor is a small non-coding RNA that regulates gene expression. This microRNA has been identified in mouse (MI0000156, MI0000408), and in human (MI0000448, MI0000748). miR-130 appears to be vertebrate-specific miRNA and has now been predicted or experimentally confirmed in a range of vertebrate species (MIPF0000034). Mature microRNAs are processed from the precursor stem-loop by the Dicer enzyme. In this case, the mature sequence is excised from the 3' arm of the hairpin. It has been found that miR-130 is upregulated in a type of cancer called hepatocellular carcinoma. It has been shown that miR-130a is expressed in the hematopoietic stem/progenitor cell compartment but not in mature blood cells. miR-130 family miR-130/301 family MicroRNA MIR130 family miR-132/212 family MicroRNA MIR132/212 family miR-146 is a family of microRNA precursors found in mammals, including humans. The ~22 nucleotide mature miRNA sequence is excised from the precursor hairpin by the enzyme Dicer. This sequence then associates with RISC which effects RNA interference.miR-146 is primarily involved in the regulation of inflammation and other process that function in the innate immune system. Loss of functional miR-146 (and mir-145) could predispose an individual to suffer from chromosome 5q deletion syndrome. miR-146 has also been reported to be highly upregulated in osteoarthritis cartilage, and could be involved in its pathogenesis. mir-146 expression is associated with survival in triple negative breast cancer. MIR146 miR-146 family MicroRNA MIR146 family MIR146 In molecular biology, miR-148 is a microRNA whose expression has been demonstrated in human (MI0000253), mouse (MI0000550), rat (MI0000616) and zebrafish (MI0002015). miR-148 has also been predicted in chicken (MI0001189). These predicted hairpin precursor sequence are related to those of miR-152, which has been expressed in mouse (MI0000174) and is predicted in human (MI0000462).The hairpin precursors (represented here) are predicted based on base pairing and cross-species conservation; their extents are not known. In this case, the mature sequence is excised from the 3' arm of the hairpin. miR-148 family miR-148/152 family MicroRNA MIR148/152 family In molecular biology miR-181 microRNA precursor is a small non-coding RNA molecule. MicroRNAs (miRNAs) are transcribed as ~70 nucleotide precursors and subsequently processed by the RNase-III type enzyme Dicer to give a ~22 nucleotide mature product. In this case the mature sequence comes from the 5' arm of the precursor. They target and modulate protein expression by inhibiting translation and / or inducing degradation of target messenger RNAs. This new class of genes has recently been shown to play a central role in malignant transformation. miRNA are downregulated in many tumors and thus appear to function as tumor suppressor genes. The mature products miR-181a, miR-181b, miR-181c or miR-181d are thought to have regulatory roles at posttranscriptional level, through complementarity to target mRNAs. miR-181 which has been predicted or experimentally confirmed in a wide number of vertebrate species as rat, zebrafish, and in the pufferfish (see below) (MIPF0000007). MIR181 miR-181 family MicroRNA MIR181 family MIR181 The miR-192 microRNA precursor (homologous to miR-215), is a short non-coding RNA gene involved in gene regulation. miR-192 and miR-215 have now been predicted or experimentally confirmed in mouse and human.microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. In this case the mature sequence comes from the 5' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA.mir-192 and mir-215 are thought to be positive regulators of p53, a human tumour suppressor. They are also overexpressed in gastric cancer, and could be used as biomarkers or therapeutic targets. It has also been suggested that mir-192 could be used as a biomarker for drug-induced liver damage. miR-192 family miR-192/215 family MicroRNA MIR192/215 family 5-hydroxytryptamine (serotonin) receptors, ionotropic HTR3 serotonin receptors, ionotropic 5-hydroxytryptamine receptors, ionotropic HTR3 In molecular biology, miR-194 microRNA precursor is a small non-coding RNA gene that regulated gene expression. Its expression has been verified in mouse (MI0000236, MI0000733) and in human (MI0000488, MI0000732). mir-194 appears to be a vertebrate-specific miRNA and has now been predicted or experimentally confirmed in a range of vertebrate species (MIPF0000055). The mature microRNA is processed from the longer hairpin precursor by the Dicer enzyme. In this case, the mature sequence is excised from the 5' arm of the hairpin. MIR194 miR-194 family MicroRNA MIR194 family MIR194 miR-196 is a non-coding RNA called a microRNA that has been shown to be expressed in human (MI0000238, MI0000279) and mouse (MI0000552, MI0000553). miR-196 appears to be a vertebrate specific microRNA and has now been predicted or experimentally confirmed in a wide range of vertebrate species (MIPF0000031). In many species the miRNA appears to be expressed from intergenic regions in HOX gene clusters. The hairpin precursors are predicted based on base pairing and cross-species conservation—their extents are not known. In this case the mature sequence is excised from the 5' arm of the hairpin. It has been suggested that a rare SNP (rs11614913) that overlaps has-mir-196a2 has been found to be associated with non-small cell lung carcinoma. MIR196 miR-196 family MicroRNA MIR196 family MIR196 The miR-199 microRNA precursor is a short non-coding RNA gene involved in gene regulation. miR-199 genes have now been predicted or experimentally confirmed in mouse, human and a further 21 other species. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The mature products are thought to have regulatory roles through complementarity to mRNA. MIR199 miR-199 family MicroRNA MIR199 family MIR199 In molecular biology miR-203 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed messenger RNA cleavage. miR-203 has been identified as a skin-specific microRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells. It has also been found upregulated in psoriasis and differentially expressed in some types of cancer. MIR203 miR-203 family MicroRNA MIR203 family MIR203 miR204/211 family MicroRNA MIR204/211 family MIR208 miR-208 family MicroRNA MIR208 family MIR208 miR-218 microRNA precursor is a small non-coding RNA that regulates gene expression by antisense binding. miR-218 appears to be a vertebrate specific microRNA and has now been predicted and experimentally confirmed in a wide range of vertebrate species. The extents of the hairpin precursors are not known. In this case the mature sequence in excised from the 5'arm of the hairpin. miR-218 is specifically expressed by mammalian motor neurons during embryonic development into adulthood, and motor neurons lacking expression of miR-218 exhibit hyperexcitability, neuromuscular junction failure, and neurodegeneration, as demonstrated by knockout mouse models.The involvement of miR-218 in cancer has also been investigated. miR-218, along with miR-585, has been found to be silenced by DNA methylation in oral squamous cell carcinoma. It is also downregulated in Nasopharyngeal carcinoma, with artificially-induced expression serving to slow tumour growth. miR-218 has also been found to have tumour suppressing qualities in bladder cancer cells. miR-218 expression was associated with overall survival in breast cancer datasets. MIR218 miR-218 family MicroRNA MIR218 family MIR218 MIR451 miR-451 family MicroRNA MIR451 family MIR451 Ribosomal biogenesis factors Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the presynaptic and postsynaptic sides of the neuromuscular junction. As ionotropic receptors, nAChRs are directly linked to ion channels and do not use second messengers (as metabotropic receptors do). Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Like the other type of acetylcholine receptor - muscarinic acetylcholine receptor (mAChR) - nAChR is triggered by the binding of the neurotransmitter acetylcholine (ACh). Just as muscarinic receptors are named such because they are also activated by muscarine, nicotinic receptors can be opened not only by acetylcholine but also by nicotine —hence the name 'nicotinic.' In insects, the cholinergic system is limited to the central nervous system. In contrast, neuronal receptors are found in both the central nervous system and the peripheral nervous system of mammals. Mammalian neuromuscular receptors are found in the neuromuscular junctions of somatic muscles ; stimulation of these receptors causes muscular contraction. CHRN Cholinergic receptors nicotinic subunits CHRN The PeBoW complex is essential for cell proliferation and maturation of the large ribosomal subunit in mammalian cells. PeBoW complex DDS complex subunits Dehydrodolichyl diphosphate synthase Erythrocyte band 7 integral membrane protein family STOM Stomatin family STOM MIR7 miR-7 family MicroRNA MIR7 family MIR7 miR-15 family miR-16 family MicroRNA MIR15/16 family The miR-24 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a mature ~22 nucleotide product. In this case the mature sequence comes from the 3' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA. miR-24 is conserved in various species, and is clustered with miR-23 and miR-27, on human chromosome 9 and 19. Recently, miR-24 has been shown to suppress expression of two crucial cell cycle control genes, E2F2 and Myc in hematopoietic differentiation and also to promote keratinocyte differentiation by repressing actin-cytoskeleton regulators PAK4, Tsk5 and ArhGAP19. MIR24 miR-24 family MicroRNA MIR24 family MIR24 The miR-26 microRNA is a small non-coding RNA that is involved in regulating gene expression. The miR-26 family is composed of miR-26a-1, miR-26a-2 and miR-26b located in chromosomes 3, 12 and 2, respectively. Pre-miR-26 with stem-loop structure is processed into mature miR-26 by a series of enzymes of intranuclear and intracytoplasm. The mature miRNA of miR-26a-1 and miR-26a-2 possesses the same sequence, with the exception of 2 different nucleotides in mature miR-26b. miR-26 appears to be a vertebrate specific microRNA and has now been predicted or experimentally validated in many vertebrate species (MIPF0000043). MIR26 miR-26 family MicroRNA MIR26 family MIR26 MIR27 miR-27 family MicroRNA MIR27 family MIR27 miR-30 microRNA precursor is a small non-coding RNA that regulates gene expression. Animal microRNAs are transcribed as pri-miRNA (primary miRNA) of varying length which in turns are processed in the nucleus by Drosha into ~70 nucleotide stem-loop precursor called pre-miRNA (precursor miRNA) and subsequently processed by the Dicer enzyme to give a mature ~22 nucleotide product. In this case the mature sequence comes from both the 3' (miR-30) and 5' (mir-97-6) arms of the precursor. The products are thought to have regulatory roles through complementarity to mRNA.A screen of 17 miRNAs that have been predicted to regulate a number of breast cancer associated genes found variations in the microRNAs. miR-17 and miR-30c-1, these patients were noncarriers of BRCA1 or BRCA2 mutations, lending the possibility that familial breast cancer may be caused by variation in these miRNAs.Members of the miR-30 family have been found to be highly expressed in heart cells. MIR30 miR-30 family MicroRNA MIR30 family MIR30 miR-33 is a family of microRNA precursors, which are processed by the Dicer enzyme to give mature microRNAs. miR-33 is found in several animal species, including humans. In some species there is a single member of this family which gives the mature product mir-33. In humans there are two members of this family called mir-33a and mir-33b, which are located in intronic regions within two protein-coding genes for Sterol regulatory element-binding proteins (SREBP-2 and SREBP-1) respectively. MIR33 miR-33 family MicroRNA MIR33 family MIR33 IFN regulatory factors IRF Interferon regulatory factors IRF CAK complex CDK activating kinase complex Transcription factor II Human (Transcription Factor II H; TFIIH) is an important protein complex, having roles in transcription of various protein-coding genes and DNA nucleotide excision repair (NER) pathways. TFIIH first came to light in 1989 when general transcription factor-δ or basic transcription factor 2 was characterized as an indispensable transcription factor in vitro. This factor was also isolated from yeast and finally named as TFIIH in 1992.TFIIH consists of ten subunits, 7 of which (ERCC2/XPD, ERCC3/XPB, GTF2H1/p62, GTF2H4/p52, GTF2H2/p44, GTF2H3/p34 and GTF2H5/TTDA) form the core complex. The cyclin activating kinase-subcomplex (CDK7, MAT1, and cyclin H) is linked to the core via the XPD protein Two of the subunits, ERCC2/XPD and ERCC3/XPB, have helicase and ATPase activities and help create the transcription bubble. In a test tube these subunits are only required for transcription if the DNA template is not already denatured or if it is supercoiled. Two other TFIIH subunits, CDK7 and cyclin H, phosphorylate serine amino acids on the RNA polymerase II C-terminal domain and possibly other proteins involved in the cell cycle. Next to a vital function in transcription initiation, TFIIH is also involved in nucleotide excision repair. GTF2H TFIIH complex General transcription factor IIH complex subunits GTF2H Transcription factor II E (TFIIE) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. It is a tetramer of two alpha and two beta chains and interacts with TAF6/TAFII80, ATF7IP, and varicella-zoster virus IE63 protein.TFIIE recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase. Transcription factor II E is encoded by the GTF2E1 and GTF2E2 genes. TFIIE is thought to be involved in DNA melting at the promoter: it contains a zinc ribbon motif that can bind single stranded DNA. GTF2E General transcription factor IIE complex subunits GTF2E GTF3C General transcription factor IIIC complex subunits GTF3C Transcription factor TFIIA is a nuclear protein involved in the RNA polymerase II-dependent transcription of DNA. TFIIA is one of several general (basal) transcription factors (GTFs) that are required for all transcription events that use RNA polymerase II. Other GTFs include TFIID, a complex composed of the TATA binding protein TBP and TBP-associated factors (TAFs), as well as the factors TFIIB, TFIIE, TFIIF, and TFIIH. Together, these factors are responsible for promoter recognition and the formation of a transcription preinitiation complex (PIC) capable of initiating RNA synthesis from a DNA template. GTF2A General transcription factor IIA complex subunits GTF2A Depalmitoylases An acetylcholine [cholinergic] receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. AChR Acetylcholine receptors Cholinergic receptors Transcription factor IIF (TFIIF) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex.Transcription factor IIF is encoded by the GTF2F1, GTF2F2, and GTF2F2L genes.TFIIF binds to RNA Polymerase II when the enzyme is already unbound to any other transcription factor, thus avoiding it from contacting DNA outside the promoter. Furthermore, TFIIF stabilizes the RNA polymerase II while it's contacting TBP and TFIIB. GTF2F General transcription factor IIF complex subunits GTF2F Fanconi anemia CC fanconi anemia core complex FA core complex The IPT (Ig-like, plexins, transcription factors) domain has an immunoglobulin like fold. These domains are found in cell surface receptors such as Met and Ron as well as in intracellular transcription factors where it is involved in DNA binding. The Ron tyrosine kinase receptor shares with the members of its subfamily (Met and Sea) a unique functional feature: the control of cell dissociation, motility, and invasion of extracellular matrices (scattering). Immunoglobulin-like fold, plexins, transcription factors TIG domain containing Transcription factor immunoglobulin domain containing immunoglobulin-plexin-transcription domain containing IPT domain containing miR-101 microRNA precursor is a small non-coding RNA that regulates gene expression. Expression of miR-101 has been validated in both human (MI0000103, MI0000739) and mouse (MI0000148). This microRNA appears to be specific to the vertebrates and has now been predicted or confirmed in a wide range of vertebrate species (MIPF0000046). The precursor microRNA is a stem-loop structure of about 70 nucleotides in length that is processed by the Dicer enzyme to form the 21-24 nucleotide mature microRNA. In this case the mature sequence is excised from the 3' arm of the hairpin. Survival analysis shows that hsa-miR-101 is associated with survival in multiple breast cancer datasets. miR101 family MicroRNA MIR101 family The miR-103 microRNA precursor (homologous to miR-107), is a short non-coding RNA gene involved in gene regulation. miR-103 and miR-107 have now been predicted or experimentally confirmed in human.microRNAs are transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. In this case the mature sequence comes from the 5' arm of the precursor. The mature products are thought to have regulatory roles through complementarity to mRNA.mir-103 and mir-107 were noted as being upregulated in obese mice and were subsequently found to have a key role in insulin sensitivity. This led to a suggestion that these microRNAs represent potential targets for the treatment of type 2 diabetes.mir-103 has also been linked with chronic pain and intestinal cell proliferation.Recently, miR-103-3p was shown to target the 5' untranslated region (5' UTR) of GPRC5A's mRNA in pancreatic cancer. This is one of only a handful of known instances where a miRNA targets the 5' UTR of a mRNA. MicroRNA MIR103/107 family The miR-129 microRNA precursor is a small non-coding RNA molecule that regulates gene expression. This microRNA was first experimentally characterised in mouse and homologues have since been discovered in several other species, such as humans, rats and zebrafish. The mature sequence is excised by the Dicer enzyme from the 5' arm of the hairpin. It was elucidated by Calin et al. that miR-129-1 is located in a fragile site region of the human genome near a specific site, FRA7H in chromosome 7q32, which is a site commonly deleted in many cancers. miR-129-2 is located in 11p11.2. MIR129 miR-129 family MicroRNA MIR129 family MIR129 The miR-135 microRNA precursor is a small non-coding RNA that is involved in regulating gene expression. It has been shown to be expressed in human, mouse and rat. miR-135 has now been predicted or experimentally confirmed in a wide range of vertebrate species (MIPF0000028). Precursor microRNAs are ~70 nucleotides in length and are processed by the Dicer enzyme to produce the shorter 21-24 nucleotide mature sequence. In this case the mature sequence is excised from the 5' arm of the hairpin. MIR135 miR-135 family MicroRNA MIR135 family MIR135 miR-138 is a family of microRNA precursors found in animals, including humans. MicroRNAs are typically transcribed as ~70 nucleotide precursors and subsequently processed by the Dicer enzyme to give a ~22 nucleotide product. The excised region or, mature product, of the miR-138 precursor is the microRNA mir-138. miR-138 has been used as an example of the post-transcriptional regulation of miRNA, due to the finding that while the precursor is expressed ubiquitously, the mature product is found only in specific cell types. MIR138 miR-138 family MicroRNA MIR138 family MIR138 MIR153 miR-153 family MicroRNA MIR153 family MIR153 Zinc-activated ion channel (ZAC), is a human protein encoded by the ZACN gene. ZAC forms a cation-permeable ligand-gated ion channel of the 'Cys-loop' superfamily. The ZAC gene is present in humans and dogs, but no ortholog is thought to exist in the rat or mouse genomes. ZAC ZACN Zinc-activated channels Zinc activated channels ZACN MIR190 miR-190 family MicroRNA MIR190 family MIR190 MIR193 miR-193 family MicroRNA MIR193 family MIR193 MIR365 miR-365 family MicroRNA MIR365 family MIR365 MIR216 miR-216 family MicroRNA MIR216 family MIR216 MIR302 miR-302 family MicroRNA MIR302 family MIR302 MIR551 miR-551 family MicroRNA MIR551 family MIR551 MIR105 miR-105 family MicroRNA MIR105 family MIR105 miR-95 family miR-95/421/545/1264 family MicroRNA MIR95 family MIR147 MicroRNA MIR147 family MIR147 miR-154 family MicroRNA MIR154 family Ion channels are pore-forming membrane proteins whose functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are considered to be one of the two traditional classes of ionophoric proteins, with the other class known as ion transporters (including the sodium-potassium pump, sodium-calcium exchanger, and sodium-glucose transport proteins, amongst others). Study of ion channels ( channelomics ) often includes biophysics, electrophysiology and pharmacology, utilizing techniques including voltage clamp, patch clamp, immunohistochemistry, and RT-PCR. Ion channels miR-379 family MicroRNA MIR379 family miR-329 family mir-329/495/543 family MicroRNA MIR329 family miR-500 family miR-500/501/502/362 family MicroRNA MIR500 family MIR374 miR-374 family MicroRNA MIR374 family MIR374 The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA). RISC silencing complex RISC-loading complex RLC RNA-induced silencing complex RISC loading complex subunits MIR376 miR-376 family MicroRNA MIR376 family MIR376 MIR378 miR-387 family MicroRNA MIR378 family MIR378 miR-290–295/miR-371–373 family miR-371-373 family miR371/372 family MicroRNA MIR371 family Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical membrane potential near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells. They have a crucial role in excitable neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. VGIC Voltage gated ion channels Voltage-gated ion channels miR-515 family MicroRNA MIR515 family The chromatin-remodelling complex B-WICH specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. B-WICH complex B-WICH chromatin-remodelling complex subunits miR-506 family MicroRNA MIR506 family MIR450 miR-450 family MicroRNA MIR450 family MIR450 Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions ( Na +) through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change ('Voltage-gated,' 'voltage-sensitive,' or 'voltage-dependent' sodium channel also called 'VGSCs' or 'Nav channel') or a binding of a substance (a ligand ) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. Sodium channels MIR486 miR-486 family MicroRNA MIR486 family MIR486 LACTB family Serine beta lactamase family PALM Paralemmins PALM The WAVE regulatory complex (WRC) is a five-subunit protein complex in the Wiskott-Aldrich syndrome protein (WASP) family involved in the formation of the actin cytoskeleton through interaction with the Arp2/3 complex. The holocomplex comprises WAVE1 (also known as WASF1), CYFIP1, ABI2, Nap1 and HSPC300 in its canonical form, or orthologues of these. WAVE regulatory complex SCAR/WAVE complex miR-888 family miR-888/890/893 family MicroRNA MIR888 family MIR891 miR-891 family MicroRNA MIR891 family MIR891 MIR544 miR-544 family MicroRNA MIR544 family MIR544 All members of the major cadherin (CDH) gene family encode proteins with an ectodomain comprising at least five consecutive cadherin repeats showing high sequence conservation within the family. The family includes the 'classical' type I and type II cadherin genes, encoding proteins with a single transmembrane domain and a cytoplasmic domain containing two conserved motifs for binding to members of the armadillo protein family. Further, the family includes type-III, type-IV and desmosomal cadherins, often encoding longer ectodomains with additional motifs, a single transmembrane domain and a cytoplasmic domain containing at least one conserved motif for armadillo protein binding. Finally, the family includes Flamingo/CELSR genes encoding proteins, which typically have a longer ectodomain, a seven-pass membrane domain and an unrelated cytoplasmic domain compared to other cadherins. These subfamilies are phylogenetically grouped together in one major cadherin branch. CDH Major cadherins CDH Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system. Muscarinic receptors were named as such because they are more sensitive to muscarine than to nicotine. Their counterparts are nicotinic acetylcholine receptors (nAChRs), receptor ion channels that are also important in the autonomic nervous system. Many drugs and other substances (for example pilocarpine and scopolamine ) manipulate these two distinct receptors by acting as selective agonists or antagonists. CHRM Muscarinic acetylcholine receptors Muscarinic receptors mAChRs Cholinergic receptors muscarinic CHRM MIR550 miR-550 family MicroRNA MIR550 family MIR550 CNNM, SLC70 Cyclin M Mg2+ exporter family Cyclin and CBS domain divalent metal cation transport mediators Solute carrier family 70 Solute carrier family 70, cyclin and CBS domain divalent metal cation transport mediators CNNM, SLC70 IKB kinases IKK family IkappaB kinases IκB Kinases I kappa B kinases miR-28 family miR-28/151 family MicroRNA MIR28/151 family In molecular biology mir-320 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. The biogenesis of miR-320 is different from the canonical Microprocessor-dependent miRNAs. The pre-miR-320 is transcribed directly as a precursor microRNA hairpin and thus contains a 5' m7G-cap. MIR320 miR-320 family MicroRNA MIR320 family MIR320 miR188/532 family MicroRNA MIR188/532 family miR-548 family MicroRNA MIR548 family In molecular biology mir-663 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. MIR663 miR-663 family MicroRNA MIR663 family MIR663 DPH Diphthamide biosynthesis genes DPH MIR664 miR-664 family MicroRNA MIR664 family MIR664 Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors. Dopamine receptors are implicated in many neurological processes, including motivation, pleasure, cognition, memory, learning, and fine motor control, as well as modulation of neuroendocrine signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders. Thus, dopamine receptors are common neurologic drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors. DRD Dopamine receptors DRD MIR1255 miR-1255 family MicroRNA MIR1255 family MIR1255 Histidine triad superfamily CAMSAP Calmodulin regulated spectrin associated proteins Patronin family ssp4 family CAMSAP family CAMSAP ELMOD ELMOD proteins ELMO domain containing ELMOD FAM83 Family with sequence similarity 83 FAM83 KCTD Potassium channel tetramerization domain family KCTD family KCTD BMERB bMERB domain containing proteins Bivalent Mical/EHBP Rab binding domain containing BMERB The IκB kinase (IKK) is an enzyme complex that is involved in propagating the cellular response to inflammation.The IκB kinase enzyme complex is part of the upstream NF-κB signal transduction cascade. The IκBα (inhibitor of kappa B) protein inactivates the NF-κB transcription factor by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. Specifically, IKK phosphorylates the inhibitory IκBα protein. This phosphorylation results in the dissociation of IκBα from NF-κB. NF-κB, which is now free, migrates into the nucleus and activates the expression of at least 150 genes; some of which are anti-apoptotic. IκB kinase (IKK) complex canonical IKK complex IKK complex RNAs, variant U1 small nuclear RNVU1 vU1 snRNAs variant U1 snRNAs Variant U1 small nuclear RNAs RNVU1 A calcium channel is an ion channel which displays selective permeability to calcium ions. It is sometimes synonymous as voltage-dependent calcium channel, although there are also ligand-gated calcium channels. Calcium channels ZUFSP deubiquitinase ZUP ZUP1 deubiquitinase ZUP ENPP Ectonucleotide pyrophosphatase/phosphodiesterase family ENPP E-NTPDases Ecto-nucleoside triphosphate diphosphohydrolase Ectonucleoside triphosphate diphosphohydrolase family PPR proteins PTCD Pentatricopeptide repeat containing PTCD B7 is a type of peripheral membrane protein found on activated antigen presenting cells (APC) that, when paired with either a CD28 or CD152 (CTLA-4) surface protein on a T cell, can produce a costimulatory signal or a coinhibitory signal to enhance or decrease the activity of a MHC-TCR signal between the APC and the T cell, respectively. Binding of the B7 of APC to CTLA-4 of T-cells causes inhibition of the activity of T-cells. There are two major types of B7 proteins: B7-1 or CD80, and B7-2 or CD86. However, it is not known if they differ significantly from each other. CD28 and CTLA-4 each interact with both B7-1 and B7-2. B7 family GBP Guanylate binding proteins GBP EB family MAPRE Microtubule end-binding proteins Microtubule associated protein RP/EB family MAPRE Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton. It is found in all eukaryotic organisms in most cells. Profilin is important for spatially and temporally controlled growth of actin microfilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such as organ development, wound healing, and the hunting down of infectious intruders by cells of the immune system. Profilin also binds sequences rich in the amino acid proline in diverse proteins. While most profilin in the cell is bound to actin, profilins have over 50 different binding partners. Many of those are related to actin regulation, but profilin also seems to be involved in activities in the nucleus such as mRNA splicing.Profilin binds some variants of membrane phospholipids (phosphatidylinositol (4,5)-bisphosphate and inositol trisphosphate). The function of this interaction is the sequestration of profilin in an 'inactive' form, from where it can be released by action of the enzyme phospholipase C. Profilin is the major allergen present in birch, grass, and other pollen and is found in Toxoplasma gondii as an essential part of host cell invasion. It is the specific pathogen-associated molecular pattern (PAMP) of TLR11. PFN Profilins PFN SLITRK SLIT and NTRK like family SLITRK TAFA TAFA chemokine like family TAFA In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium -selective pores that span cell membranes. Furthermore potassium channels are found in most cell types and control a wide variety of cell functions. KCN Potassium channels KCN TTYH Tweety family TTYH TOR Torsin ATPases Torsins TOR THEM Thioesterase superfamily THEM CT antigen 5 family SSX Synovial sarcoma X chromosome breakpoint family SSX family SSX CT antigen 11 family Sperm protein associated with the nucleus on the X chromosome family SPANX family These protein coding genes host snoRNA genes in their introns. snoRNA protein coding host genes Small nucleolar RNA protein coding host genes IGFL IGF like family IGFL CELA Pancreatic elastases Chymotrypsin like elastases CELA In the human genome, most snoRNA genes are located within the introns of other 'host' genes. Such snoRNA host genes can be either protein-coding or non-coding. snoRNA host genes Small nucleolar RNA host genes Long non-coding genes that host snoRNA genes in either an intron or an exon on the same strand are named with the root symbol SNHG for 'small nucleolar RNA host gene', followed by a sequential number e.g. SNHG1 for 'small nucleolar RNA host gene 1'. SNHG Small nucleolar RNA non-coding host genes SNHG Nav channels SCN VGSCs Voltage-dependent sodium channels Voltage-gated sodium channels Voltage-sensitive sodium channels Sodium voltage-gated channels SCN ITIH Inter-alpha-trypsin inhibitor heavy chains ITIH Epitempin family LGI Leucine rich repeat LGI family Leucine-rich, glioma-inactivated family LGI family LGI N-myc downstream regulated gene family NDRG NDRG family NDRG CT antigen 12 family X antigen family XAGE XAGE family XAGE CT antigen 4 family G antigen family GAGE GAGE family GAGE CT antigen 16 family PAGE PAGE family PAGE CT antigen 14 family SAGE Sarcoma antigen family SAGE family SAGE B melanoma antigen family BAGE CT antigen 2 family BAGE family BAGE CT45 Cancer/testis antigen family 45 CT antigen family 45 CT45 ENaC Epithelial sodium channels Ligand-gated sodium channels SCNN Sodium channels, non voltage gated Sodium channels epithelial SCNN CT47 CT antigen family 47 CT47 CSAG CT antigen family 24 Chondrosarcoma associated gene family CSAG family CSAG Mitochondrial iron-sulfur assembly components Fe-S assembly components Iron-sulfur assembly components Nectins and Nectin-like molecules (Necl) are families of cellular adhesion molecules involved in Ca2+-independent cellular adhesion.Nectins are ubiquitously expressed and have adhesive roles in a wide range of tissues such as the adherens junction of epithelia or the chemical synapse of the neuronal tissue. Nectins and nectin-like molecules Golgin related Tim17 family MIR1302 miR-1302 family MicroRNA MIR1302 family MIR1302 MIR1184 miR-1184 family MicroRNA MIR1184 family MIR1184 The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca 2+ channels that seem to be specific to sperm. As sperm encounter the more alkaline environment of the female reproductive tract, CatSper channels become activated by the altered ion concentration. These channels are required for proper fertilization. The study of these channels has been slow because they do not traffic to the cell membrane in many heterologous systems. CATSPER CATSPER channels Cation channels of sperm Cation channels sperm associated CATSPER MIR1233 miR-1233 family MicroRNA MIR1233 family MIR1233 MIR1244 miR-1244 family MicroRNA MIR1244 family MIR1244 MIR1285 MicroRNA MIR1285 family MIR1285 MIR1289 MicroRNA MIR1289 family MIR1289 MIR1972 miR-1972 family MicroRNA MIR1972 family MIR1972 MIR3118 miR-3118 family MicroRNA MIR3118 family MIR3118 MIR3156 miR-3156 family MicroRNA MIR3156 family MIR3156 MIR3179 miR-3179 family MicroRNA MIR3179 family MIR3179 MIR3180 miR-3180 family MicroRNA MIR3180 family MIR3180 The histamine receptors are a class of G protein-coupled receptors with histamine as their endogenous ligand. There are four known histamine receptors: H 1 receptor H 2 receptor H 3 receptor H 4 receptor HRH Histamine receptors HRH MIR3198 miR-3198 family MicroRNA MIR3198 family MIR3198 MIR3648 miR-3648 family MicroRNA MIR3648 family MIR3648 MIR3670 miR-3670 family MicroRNA MIR3670 family MIR3670 MIR3680 miR-3680 family MicroRNA MIR3680 family MIR3680 N-CoR complex SMRT/NCoR-HDAC3 complex SMRT–HDAC3 repression complex NCoR/SMRT transcriptional repression complex subunits The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein (protein-RNA complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes. Signal recognition particle These cytoplasmic tRNAs are not included in the high confidence set at the Genomic tRNA database. They may have low tRNAscan feature scores and may possibly be repeat elements or pseudogenes. Low confidence cytoplasmic tRNAs Low confidence cytoplasmic transfer RNAs Transcription factor II D (TFIID) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters of protein-coding genes in living cells. It consists of RNA polymerase II, a subset of general transcription factors, and regulatory proteins known as SRB proteins. Before the start of transcription, the transcription Factor II D (TFIID) complex binds to the TATA box in the core promoter of the gene. TAF TFIID Transcription factor II D General transcription factor IID complex subunits TAF TFIIIB General transcription factor IIIB complex subunits Trace amine-associated receptors, abbreviated TAAR and otherwise known as trace amine receptors, abbreviated TAR or TA, are a class of G protein-coupled receptors identified in 2001. These receptors have gained considerable interest in academic and pharmaceutical industry research as putative endogenous receptors for trace amines, metabolic derivatives of classical biogenic amines and the psychostimulants amphetamine and methamphetamine. In 2004 it was shown that in mammals TAAR1 is probably also a receptor for thyronamines, decarboxylated and deiodinated metabolites of the thyroid hormones, while the mouse mTAAR2 -€“ mTAAR9 receptors are most probably olfactory receptors for volatile amines. TA TAAR TAR Trace amine receptors TAAR Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the RUNX1 gene. RUNX1 is a transcription factor that regulates the differentiation of hematopoietic stem cells into mature blood cells. In addition it plays a major role in the development of the neurons that transmit pain. It belongs to the Runt-related transcription factor (RUNX) family of genes which are also called core binding factor-α (CBFα). RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex. Chromosomal translocations involving the RUNX1 gene are associated with several types of leukemia including M2 AML. Mutations in RUNX1 are implicated in cases of breast cancer. RUNX RUNX transcription factors Runt-related transcription factors RUNX BRAG family IQSEC IQSEC ARF-GEFs IQSEC family IQSEC ARFGEF family IQSEC MAB21 Male abnormal 21 family MAB21 family MAB21 TXNDC Thioredoxin domain containing TXNDC HERC HERC family ubiquitin ligases HECT and RLD domain containing E3 ubiquitin protein ligases HERC ATL Atlastin GTPases Atlastins ATL FBN Fibrillins Fibrillin family FBN FLN Filamins FLN Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 19 distinct chemokine receptors described in mammals. Each has a 7- transmembrane (7TM) structure and couples to G-protein for signal transduction within a cell, making them members of a large protein family of G protein-coupled receptors. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium (Ca 2+ ) ions ( calcium signaling ). This causes cell responses, including the onset of a process known as chemotaxis that traffics the cell to a desired location within the organism. Chemokine receptors are divided into different families, CXC chemokine receptors, CC chemokine receptors, CX3C chemokine receptors and XC chemokine receptors that correspond to the 4 distinct subfamilies of chemokines they bind. Chemokine receptors The Bag6 complex is involved in tail-anchored protein targeting and various protein quality-control pathways in the cytosol as well as regulating transcription and histone methylation in the nucleus. BAG6/BAT3 complex BAG6 complex DPM Dolichol-phosphate mannosyltransferase complex Dolichyl-phosphate mannosyltransferase subunits DPM KDELR KDEL endoplasmic reticulum protein retention receptors KDELR FGF Fibroblast growth factor family FGF Glycoprotein hormone subunits R-spondins RSPO R-spondin family RSPO WNK with no lysine (K) kinases WNK lysine deficient protein kinases WNK The protocadherin (PCDH) gene family encodes proteins with an ectodomain comprising six or seven cadherin repeats with high sequence conservation within the family and weaker homology to the cadherin repeats of members of the major cadherin family. Further, protocadherins have a single transmembrane domain and a distinct, protocadherin-specific, cytoplasmic domain. Protocadherins can be further subdivided into clustered and non-clustered protocadherins on the basis of particular genomic organizations. PCDH Protocadherins PCDH Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. AKT AKT kinases AKT serine/threonine kinases protein kinase B family AKT kinase family AKT TAC Tachykinins Tachykinin precursors TAC Neuropeptides Aldolase A (ALDOA, or ALDA), also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ALDOA gene on chromosome 16. The protein encoded by this gene is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP). Three aldolase isozymes (A, B, and C), encoded by three different genes, are differentially expressed during development. Aldolase A is found in the developing embryo and is produced in even greater amounts in adult muscle. Aldolase A expression is repressed in adult liver, kidney and intestine and similar to aldolase C levels in brain and other nervous tissue. Aldolase A deficiency has been associated with myopathy and hemolytic anemia. Alternative splicing and alternative promoter usage results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 3 and 10. [provided by RefSeq, Aug 2011] ALDO fructose-bisphosphate aldolases Aldolases ALDO EDN Endothelins EDN CNTN Contactins CNTN LAMP Lysosome associated membrane proteins LAMP EMC EMC subunits ER membrane protein complex subunits EMC Get3/TRC40 function requires an ER receptor, which in yeast consists of the Get1/Get2 heterotetramer and in mammals of the WRB protein (now approved as GET1 in human), homologous to yeast Get1, in combination with CAML (calcium-modulating cyclophilin ligand), which is not homologous to Get2. GET GET complex Guided Entry of TA Proteins complex Guided entry of tail-anchored proteins complex subunits GET In yeast, Get4 and Get5 escort tail-anchored proteins to Get3. In mammals, BAG6, (which lacks a yeast equivalent) is additionally required to enable an otherwise similar TA protein transfer process. Get4/Get5 complex TMD complex TRC complex GET4-GET5 transmembrane domain recognition complex subunits The GET (guided entry of tail-anchored proteins)/TRC (transmembrane recognition complex) pathway for tail-anchored protein targeting to the endoplasmic reticulum (ER) has been characterized in detail in yeast and is thought to function similarly in mammals. Guided entry of tail-anchored proteins associated factors ASC-1 ASCC hASC-1 Activating signal cointegrator 1 complex ASCC COP COPI coatomer Coat protein complex I COP TMTC Transmembrane and tetratricopeptide repeat containing Transmembrane O-mannosyltransferase targeting cadherins TMTC Arfaptin homology domain containing Arfaptin-like domain containing AH domain containing AH/BAR family Rho GAPs AH/BAR family Rho GTPase activating proteins BAR and Dbl domain containing Leprecan family P3H Prolyl 3-hydroxylase family P3H Isocitrate dehydrogenase (IDH) (EC 1.1.1.42) and (EC 1.1.1.41) is an enzyme that catalyzes the oxidative decarboxylation of isocitrate, producing alpha-ketoglutarate (α-ketoglutarate) and CO2. This is a two-step process, which involves oxidation of isocitrate (a secondary alcohol) to oxalosuccinate (a ketone), followed by the decarboxylation of the carboxyl group beta to the ketone, forming alpha-ketoglutarate. In humans, IDH exists in three isoforms: IDH3 catalyzes the third step of the citric acid cycle while converting NAD+ to NADH in the mitochondria. The isoforms IDH1 and IDH2 catalyze the same reaction outside the context of the citric acid cycle and use NADP+ as a cofactor instead of NAD+. They localize to the cytosol as well as the mitochondrion and peroxisome. IDH Isocitrate dehydrogenases IDH Pepsin is an endopeptidase that breaks down proteins into smaller peptides (that is, a protease). It is produced in the stomach and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pepsin is an aspartic protease, using a catalytic aspartate in its active site.It is one of three principal proteases in the human digestive system, the other two being chymotrypsin and trypsin. During the process of digestion, these enzymes, each of which is specialized in severing links between particular types of amino acids, collaborate to break down dietary proteins into their components, i.e., peptides and amino acids, which can be readily absorbed by the small intestine. Pepsin is most efficient in cleaving peptide bonds between hydrophobic and preferably aromatic amino acids such as phenylalanine, tryptophan, and tyrosine. Pepsin's proenzyme, pepsinogen, is released by the chief cells in the stomach wall, and upon mixing with the hydrochloric acid of the gastric juice, pepsinogen activates to become pepsin. Gastric aspartic proteases Gastric aspartic proteinases Gastric aspartyl peptidases Pepsinogens Aspartic proteases are a catalytic type of protease enzymes that use an activated water molecule bound to one or more aspartate residues for catalysis of their peptide substrates. In general, they have two highly conserved aspartates in the active site and are optimally active at acidic pH. Nearly all known aspartyl proteases are inhibited by pepstatin.Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin and archaean preflagellin have been described.Eukaryotic aspartic proteases include pepsins, cathepsins, and renins. They have a two-domain structure, arising from ancestral duplication. Retroviral and retrotransposon proteases (retroviral aspartyl proteases) are much smaller and appear to be homologous to a single domain of the eukaryotic aspartyl proteases. Each domain contributes a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulfide bridges are other conserved features of aspartic peptidases. Acidic peptidases Acidic proteases Acidic proteinases Aspartic proteases Carboxyl proteinases pepsin family Peptidase family A1 SOD Superoxide dismutases SOD The yeast Dsl1 complex, which comprises Dsl1, Tip20, and Sec39/Dsl3, has been shown to participate, as a vesicle-tethering complex, in retrograde trafficking from the Golgi apparatus to the endoplasmic reticulum. Its metazoan counterpart NRZ complex, which comprises NAG, RINT1, and ZW10, is also involved in Golgi-to-ER retrograde transport, but each component of the complex has diverse cellular functions including endosome-to-Golgi transport, cytokinesis, cell cycle checkpoint, autophagy, and mRNA decay. NRZ complex mammalian Dsl1 complex NRZ tethering complex TGF-β family TGF-β superfamily Transforming growth factor beta superfamily The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Checkpoint signalling requires the kinetochore localization of the Mad1-Mad2 complex that in more complex eukaryotes depends on the Rod-Zwilch-ZW10 (RZZ) complex. Rod-Zwilch-ZW10 complex RZZ complex Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species. H1 Linker histones H1 histones H1 Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. H2A H2A histones H2A Histone H2B is one of the 4 main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and long N-terminal and C-terminal tails, H2B is involved with the structure of the nucleosomes. H2B H2B histones H2B Histone H3 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a string' structure. Histone proteins are highly post-translationally modified however Histone H3 is the most extensively modified of the five histones. The term 'Histone H3' alone is purposely ambiguous in that it does not distinguish between sequence variants or modification state. Histone H3 is an important protein in the emerging field of epigenetics, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes. H3 H3 histones H3 Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H4 is involved with the structure of the nucleosome of the 'beads on a string' organization. Histone proteins are highly post-translationally modified. Covalently bonded modifications include acetylation and methylation of the N-terminal tails. These modifications may alter expression of genes located on DNA associated with its parent histone octamer. Histone H4 is an important protein in the structure and function of chromatin, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes. H4 H4 histones H4 The three CCM proteins can exist in a trimeric complex, and each of these essential multi-domain adaptor proteins also interacts with a range of signaling, cytoskeletal and adaptor proteins, presumably accounting for their roles in a range of basic cellular processes including cell adhesion, migration, polarity and apoptosis. CCM complex CCM signaling complex (CSC) CCM adhesion complex CAMTA Calmodulin binding transcription activators CAMTA CAV Caveolins CAV AINT family ERIC family TACC Transforming acidic coiled-coil containing family TACC family TACC NELF Negative elongation factor complex members NELF Sec7 ArfGEFs Sec7 domain containing Sec7 family CYTH Cytohesins CYTH ARFGEF BIG ArfGEF family BIG family ArfGEF family ARFGEF PSD Pleckstrin and Sec7 domain containing PSD Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation. hnRNPs are also integral to the 40s subunit of the ribosome and therefore important for the translation of mRNA in the cytoplasm. However, hnRNPs also have their own nuclear localization sequences (NLS) and are therefore found mainly in the nucleus. Though it is known that a few hnRNPs shuttle between the cytoplasm and nucleus, immunofluorescence microscopy with hnRNP-specific antibodies shows nucleoplasmic localization of these proteins with little staining in the nucleolus or cytoplasm. This is likely because of its major role in binding to newly transcribed RNAs. High-resolution immunoelectron microscopy has shown that hnRNPs localize predominantly to the border regions of chromatin, where it has access to these nascent RNAs.The proteins involved in the hnRNP complexes are collectively known as heterogeneous ribonucleoproteins. They include protein K and polypyrimidine tract-binding protein (PTB), which is regulated by phosphorylation catalyzed by protein kinase A and is responsible for suppressing RNA splicing at a particular exon by blocking access of the spliceosome to the polypyrimidine tract. hnRNPs are also responsible for strengthening and inhibiting splice sites by making such sites more or less accessible to the spliceosome. Cooperative interactions between attached hnRNPs may encourage certain splicing combinations while inhibiting others. HNRNP hnRNPs Heterogeneous nuclear ribonucleoproteins HNRNP GPI-anchor transamidase complex GPIT Glycosylphosphatidylinositol transamidase complex PANK Pantothenate kinase family PANK TMEM8 TMEM8 family TMEM8 Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase. GEFs Rho guanine nucleotide exchange factors HECT family HECT domain containing Anaphylatoxin receptors Complement peptide receptors Complement component GPCRs COPII coatomer Coat protein complex II Protein coats Protein coat complexes SMG1c SMG1 complex SURF complex Decay inducing complex DECID complex SRD5A Steroid 5-alpha reductase family SRD5A SUN proteins are type-II transmembrane proteins with nuclear-oriented N-termini and lumenal C-termini. Named for SUN domain family members (Sad1p, Unc-84) they all share a conserved SUN domain at the C-terminus of the lumenal domain. This lumenal region of SUN proteins also includes an extended coiled-coil domain. The nucleoplasmic domain of SUN proteins is structurally less characterized, but at least in some mammalian family members, has been shown to be capable of nuclear localization independent of the rest of the protein. SUN Sad1 and UNC84 domain containing SUN family SUN CASPR family CNTNAP Contactin associated protein family CNTNAP CREB3 oasis bZIP transcription factor family CREB3 transcription factor family CREB3 SHROOM Shroom family SHROOM MT- Mitochondrial genome MT- Mitochondrially encoded regions Mitochondrially encoded protein coding genes Mitochondrially encoded RNAs Mitochondrially encoded long non-coding RNAs Intraflagellar transport (IFT)-A and -B complexes mediate retrograde and anterograde ciliary protein trafficking, respectively. The IFT-A complex is divided into a core subcomplex, composed of IFT122/IFT140/IFT144, which is associated with TULP3, and a peripheral subcomplex, composed of IFT43/IFT121/IFT139, where IFT139 is most distally located. Intraflagellar transport complex A IFT-A complex IFT52 is a key component of the IFT-B complex and ensures the interaction of the two subcomplexes, IFT-B1 and IFT-B2. IFT-B complex The formyl peptide receptors (FPR) belong to a class of G protein-coupled receptors involved in chemotaxis. These receptors were originally identified by their ability to bind N-formyl peptides such as N -formylmethionine produced by the degradation of either bacterial or host cells. Hence formyl peptide receptors are involved in mediating immune cell response to infection. These receptors may also act to suppress the immune system under certain conditions. The close phylogenetical relation of signaling in chemotaxis and olfaction was recently proved by detection formyl peptide receptor like proteins as a distinct family of vomeronasal organ chemosensors in mice FPR Formyl peptide receptors FPR The IFT-B1 complex consists of 9-10 stably associated core subunits. IFT IFT-B1 complex IFT Thought to be peripheral components of the IFT-B complex, IFT172, 80, 57, 54, and 20 form a stable sub-complex (IFT-B2). IFT-B2 interacts with tubulin/microtubules and connects them to the core IFT-B1 complex through interaction with IFT88/52. IFT IFT-B2 complex IFT TN Tenascins TN RAG GTPases RRAG Ras related GTP binding proteins RRAG CAAT box transcription factors CTF family NFI Nuclear factor I family NFI The HGNC defines long intergenic non-protein coding (LINC) RNAs as long non-coding RNA genes that do not overlap on either strand, or share a bidirectional promoter with, a protein coding gene and do not host either snoRNA or microRNA genes. These lincRNA genes are assigned the root symbol LINC# for 'long intergenic non-protein coding RNA' followed by a unique 5-digit number e.g. LINC00115. LINC LINCs Long intergenic non-coding RNAs Long intervening non-coding RNAs Long intergenic non-protein coding RNAs LINC The HGNC defines antisense RNAs as long non-coding RNA genes that are on the opposite strand of the genomic span of a protein coding gene, including the intronic and UTR regions of the opposite protein coding gene. Please note this nomenclature is not intended to suggest that there is a shared function between the protein coding gene and antisense RNA. Antisense lncRNA genes are assigned the format [protein coding gene symbol]-AS + sequential number e.g. ABCA9-AS1 for 'ABCA9 antisense RNA 1'. Antisense lncRNAs Antisense long non-coding RNAs Antisense to protein coding gene long non-coding RNAs Antisense RNAs The HGNC defines overlapping transcripts as long non-coding RNA genes that overlap a protein coding gene on the same strand. These lncRNA genes are assigned the format [protein coding gene symbol]-OT + sequential number e.g. ACER2-OT1 for 'ACER2 3' UTR overlapping transcript'. Overlapping lncRNAs Overlapping long non-coding RNAs Overlapping non-coding transcripts Protein coding gene overlapping non-coding transcripts Overlapping transcripts The HGNC defines intronic transcripts as long non-coding RNA genes that are located within an intron on the SAME strand as a protein coding gene. These lncRNA genes are assigned the format [protein coding gene symbol]-IT + sequential number e.g. AKT2-IT1 for 'AKT2 intronic transcript 1'. Intronic lncRNAs Intronic long non-coding RNAs Intronic non-coding transcripts Intronic to protein coding gene long non-coding RNAs Intronic transcripts Gonadotropin and TSH receptors Glycoprotein hormone receptors The HGNC defines divergent transcripts as long non-coding RNA genes that are within 300-500 nucleotides of a protein coding gene on the opposite strand. These lncRNA genes are named with the format [protein coding gene symbol]-DT e.g. DHX33-DT for 'DHX33 divergent transcript'. Bidirectional promoter sharing lncRNAs Divergent to protein coding gene long non-coding RNAs LncRNAs divergent to protein coding genes Divergent transcripts Long non-coding RNAs with non-systematic symbols Homologous long non-coding RNA genes may be named together using the root symbol FAM# for 'family with sequence similarity'. Note that this root symbol is also used for protein coding families - this gene groups shows only the non-coding genes named with the FAM# root. FAM Long non-coding RNAs with FAM root symbol FAM 39S mitoribosome subunit proteins Large mitoribosome subunit proteins MRPL Mitochondrial ribosomal L proteins mt LSU proteins Large subunit mitochondrial ribosomal proteins MRPL 28S mitoribosome subunit proteins MRPS Mitochondrial ribosomal S proteins Small mitoribosome subunit proteins mt SSU proteins Small subunit mitochondrial ribosomal proteins MRPS HIRA histone chaperone complex subunits The eukaryotic minichromosome maintenance 2-7 complex is the core of the inactive MCM replication licensing complex and the catalytic core of the Cdc45-MCM-GINS replicative helicase. MCM complex MCM2-7 complex MCM2-7 replicative helicase MCM2-MCM7 complex minichromosome maintenance complex minichromosome maintenance 2-7 complex The CMG (Cdc45-MCM-GINS) complex is the eukaryotic replicative helicase, the enzyme that unwinds double-stranded DNA at replication forks. Cdc45-MCM-GINS complex CMG helicase complex Clustered protocadherins HCAR Nicotinic acid receptor family Hydroxycarboxylic acid receptors HCAR AMER AMER family APC membrane recruitment proteins AMER Atrophins The LINC complex (Linker of Nucleoskeleton and Cytoskeleton) is a protein complex associated with both inner and outer membranes of the nucleus. It is composed of SUN-domain proteins and KASH-domain proteins. The SUN-domain proteins are associated with both nuclear lamins and chromatin and cross the inner nuclear membrane. They interact with the KASH domain proteins in the perinuclear (lumen) space between the two membranes. The KASH domain proteins cross the outer nuclear membrane and interact with actin filaments, microtubule filaments (through dynein and kinesin motors), intermediate filaments (through spectrin), centrosomes and cytoplasmic organelles. The number of SUN-domain and KASH-domain proteins increased in evolution. LINC complex nucleoplasmic bridging complex Linker of nucleoskeleton and cytoskeleton complex subunits Formins R2SP complex Lipid like receptors KASH domains are conserved C-terminal protein regions less than ~30 amino acids. KASH is an acronym for Klarsicht, ANC-1, Syne Homology. KASH domains always follow a transmembrane domain. Most proteins containing KASH domains are thought to be involved in the positioning of the nucleus in the cell. KASH domains interact with proteins containing SUN domains in the space between the outer and inner nuclear membranes to bridge the nuclear envelope, and may transfer force from the nucleoskeleton to the cytoplasmic cytoskeleton and enable mechanosensory roles in cells. KASH proteins are thought to largely localize to the outer nuclear membrane, although there are reports of inner nuclear membrane localization of some KASH protein isoforms. KASH domain containing The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex) FHF complex The outer dynein arm-docking complex (ODA-DC), which was first identified in the green alga Chlamydomonas reinhardtii, is a protein complex that mediates the binding of axonemal dynein and doublet microtubules. ODA-DC ODAD Outer dynein arm docking complex subunits ODAD The cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains. Cannabinoid receptors are activated by three major groups of ligands, endocannabinoids (produced by the mammalian body), plant cannabinoids (such as THC, produced by the cannabis plant) and synthetic cannabinoids (such as HU-210 ). All of the endocannabinoids and plant cannabinoids are lipophilic, i.e. fat soluble, compounds. There are currently two known subtypes, termed CB 1 and CB 2. The CB 1 receptor is expressed mainly in the brain ( central nervous system or 'CNS'), but also in the lungs, liver and kidneys. The CB 2 receptor is expressed mainly in the immune system and in hematopoietic cells. Mounting evidence suggests that there are novel cannabinoid receptors that is, non-CB 1 and non-CB 2, which are expressed in endothelial cells and in the CNS. In 2007, the binding of several cannabinoids to a G protein-coupled receptor (GPCR) in the brain was described. The protein sequences of CB 1 and CB 2 receptors are about 44% similar. When only the transmembrane regions of the receptors are considered, amino acid similarity between the two receptor subtypes is approximately 68%. In addition, minor variations in each receptor have been identified. Cannabinoids bind reversibly and stereo-selectively to the cannabinoid receptors. Subtype selective cannabinoids have been developed which theoretically may have advantages for treatment of certain diseases such as obesity. CNR Cannabinoid receptors CNR Type II transmembrane serine proteases IQGAP IQGAP scaffold proteins IQ motif containing GTPase activating protein family IQGAP 2-oxoglutarate dehydrogenase complex KGDHC Ketoglutarate dehydrogenase complex Mitochondrial oxoglutarate dehydrogenase complex OGDC alpha-ketoglutarate dehydrogenase complex Oxoglutarate dehydrogenase complex Lysine hydroxylases PLOD Procollagen lysyl hydroxylases Procollagen-lysine 5-dioxygenases Procollagen-lysine,2-oxoglutarate 5-dioxygenase family PLOD 3-hydroxyacyl-CoA dehydratases HACD 3-hydroxyacyl-CoA dehydratase family HACD Cytoplasmic dynein-1 is a major microtubule-based motor critical for cell division. Dynein is essential for the formation and positioning of the mitotic spindle as well as the transport of various cargos in the cell. DYNC1 Dynein 1 complex subunits DYNC1 The motor protein that powers the movement of the particles from the tip of the flagellum to the base (retrograde IFT) is called cytoplasmic dynein 1b in Chlamydomonas and cytoplasmic dynein 2 in vertebrates. DYNC2 IFT dynein cytoplasmic dynein-2 dynein-1b intraflagellar transport dynein Dynein 2 complex subunits DYNC2 The free fatty acid receptor is a G-protein coupled receptor which binds free fatty acids. There are four variants of the receptor, each encoded by a separate gene ( FFAR1, FFAR2, FFAR3, FFAR4). FFAR Free fatty acid receptors FFAR ADP-ribosyl-transferases clostridia toxin-like family ART ARTC family ADP-ribosyltransferase family ART axonemal outer arm dyneins ciliary axonemal outer arm dyneins outer arm dyneins (OAD) outer dynein arms (ODA) Dyneins, axonemal outer arm complex subunits axonemal inner arm I1/f dynein complex inner dynein arm (IDA) I1 complex inner dynein arm (IDA) f complex Dyneins, axonemal inner arm I1/f complex subunits DACT DACT family scaffold proteins Dapper/Frodo family Dishevelled binding antagonist of beta catenin family DACT DCLRE1 SNM1 family nucleases DNA cross-link repair family DCLRE1 Radical S-adenosylmethionine domain containing AGO Argonautes Argonaute RISC component family AGO PIWI family PIWIL Piwi like RNA-mediated gene silencing family PIWIL ELC MLC1 Myosin alkali light chains Myosin essential light chains Myosin light chains, class 1 Leukotriene receptors MLC2 Myosin phosphorylatable light chains Myosin regulatory light chains RLC Myosin light chains, class 2 CREC family MTRF mitochondrial RF-like family mitochondrial ribosome rescue factor family Mitochondrial translation release factor family MTRF A ribonucleoprotein complex that contains small nuclear RNA U11, a heptameric ring of Sm proteins, as well as several proteins that are unique to the U11 snRNP, most of which remain associated with the U11 snRNA both while the U11 snRNP is free or assembled into a series of spliceosomal complexes. 12S U11 snRNP U11 snRNP U11 small nuclear ribonucleoprotein The radial spoke is a multi-unit protein structure found in the axonemes of eukaryotic cilia and flagella. Although experiments have determined the importance of the radial spoke in the proper function of these organelles, its structure and mode of action remain poorly understood. RSPH Axonemal radial spoke subunits RSPH Methylcrotonyl-CoA carboxylase (MCCC) is a heteromultimeric complex that is composed of two subunits which are encoded by distinct genes. 3-methylcrotonyl-CoA carboxylase MCCC Methylcrotonyl-CoA carboxylase subunits MCCC AP-2 family TFAP2 Transcription factor AP-2 family TFAP2 TET ten-eleven translocation enzymes Tet methylcytosine dioxygenase family TET LPAR Lysophospholipid (LPA) receptors Lysophosphatidic acid receptors LPAR ADD Adducins Adducin family ADD GW182 family TNRC6 Trinucleotide repeat containing 6 family TNRC6 adaptor family TNRC6 PARN deadenylase family PARN exonuclease family The ATP synthase F1 domain and V-ATPase V1 domain alpha/A and beta/B subunits are encoded by homologous genes, shown together here. ATPase alpha/beta chains family ATPase F1/V1 alpha/A and beta/B subunit family seven transmembrane proteins 7TM proteins The TLDc domain is a highly conserved protein motif present in several mammal proteins that share a protective function against oxidative stress. TBC/LysM-associated domain containing TLDC TLDc domain containing TLDC 7BS methyltransferase motif lysine specific methyltranferases Seven-beta-strand methyltransferase motif containing lysine specific methyltranferases 7BS protein lysine methyltransferases Seven-beta-strand methyltransferase motif containing arginine specific methyltranferases 7BS protein arginine methyltranferases 7BS methyltransferase motif containing protein methyltransferases Seven-beta-strand methyltransferase motif containing protein methyltranferases 7BS protein methyltransferases Seven-beta-strand methyltransferase motif containing DNA/RNA methyltranferases 7BS DNA/RNA methyltransferases Lysophospholipid (S1P) receptors S1PR1 Sphingosine 1-phosphate receptors S1PR1 Seven-beta-strand methyltransferase motif containing C5-cytosine DNA/RNA methyltranferases 7BS C5-cytosine DNA/RNA methyltransferases Seven-beta-strand methyltransferase motif containing N6-adenosine DNA/RNA methyltranferases 7BS N6-adenosine DNA/RNA methyltransferases Seven-beta-strand methyltransferase motif containing 2'O-ribose DNA/RNA methyltranferases 7BS 2'O-ribose DNA/RNA methyltransferases Seven-beta-strand methyltransferase motif containing small molecule methyltranferases 7BS small molecule methyltransferases 7BS orphan methyltransferases Apelin receptor DAX-like receptors NR0B Nuclear receptor subfamily 0 group B NR0B Nuclear receptor subfamily 1 group B RAR Retinoic acid receptors RAR Prostaglandin (prostanoid) receptors Prostanoid receptors Prostaglandin receptors Nuclear receptor subfamily 1 group A THR Thyroid hormone receptors THR Nuclear receptor subfamily 1 group C PPAR Peroxisome proliferator activated receptors PPAR NR1D Rev-Erb receptors Nuclear receptor subfamily 1 group D NR1D NR2C Testicular receptors Nuclear receptor subfamily 2 group C NR2C NR2E Tailless-like receptors Nuclear receptor subfamily 2 group E NR2E COUP-TF-like receptors NR2F Nuclear receptor subfamily 2 group F NR2F 3-Ketosteroid receptors NR3C Nuclear receptor subfamily 3 group C NR3C ESR Nuclear receptor subfamily 3 group A Estrogen receptors ESR ESRR Nuclear receptor subfamily 3 group B Estrogen related receptors ESRR NR4A Nerve growth factor IB-like receptors Nuclear receptor subfamily 4 group A NR4A The platelet-activating factor receptor is a G-protein coupled receptor which binds platelet-activating factor. The PAF receptor shows structural characteristics of the rhodopsin (MIM 180380) gene family and binds platelet-activating factor (PAF). PAF is a phospholipid (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) that has been implicated as a mediator in diverse pathologic processes, such as allergy, asthma, septic shock, arterial thrombosis, and inflammatory processes.[supplied by OMIM] PTAFR Platelet activating factor receptor PTAFR Fushi tarazu F1-like receptors NR5A Nuclear receptor subfamily 5 group A NR5A Germ cell nuclear factor receptors NR6A Nuclear receptor subfamily 6 group A NR6A ROR Retinoic acid-related orphans RAR related orphan receptors ROR Liver X receptor-like receptors NR1H Nuclear receptor subfamily 1 group H NR1H NR1I Vitamin D receptor-like receptors Nuclear receptor subfamily 1 group I NR1I HNF4 Hepatocyte nuclear factor-4 receptors Nuclear receptor subfamily 2 group A Hepatocyte nuclear factor 4 family HNF4 Nuclear receptor subfamily 2 group B RXR Retinoid X receptors RXR A melatonin receptor is a G protein-coupled receptor (GPCR) which binds melatonin. Three types of melatonin receptor have been cloned. The MT 1 (or Mel 1A or MTNR1A) and MT 2 (or Mel 1B or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype MT 3 (or Mel 1C or MTNR1C) has been identified in amphibia and birds. MTNR Melatonin receptors MTNR SWI/SNF related BAF chromatin remodeling complexes GBA Glucocerebrosidases beta-glucosidases beta-glucosylceramidases Glucosylceramidases GBA In molecular biology, 2'-5'-oligoadenylate synthetase (2-5A synthetase) is an enzyme (EC 2.7.7.84) that reacts to interferon signal. It is an antiviral enzyme that counteracts viral attack by degrading RNAs, both viral and host. The enzyme uses ATP in 2'-specific nucleotidyl transfer reactions to synthesize 2'-5'-oligoadenylates, which activate latent ribonuclease (RNASEL), resulting in degradation of viral RNA and inhibition of virus replication.The C-terminal half of 2'-5'-oligoadenylate synthetase, also referred to as domain 2 of the enzyme, is largely alpha-helical and homologous to a tandem ubiquitin repeat. It carries the region of enzymatic activity between at the extreme C-terminal end. OAS OAS family 2'-5'-oligoadenylate synthetase family OAS Peptidase family A28 aspartic proteases aspartyl proteases membrane-inserted endopeptidases Peptidase family A22 Non-clustered protocadherins Nucleotide like receptors CFIm Cleavage factor I(m) mammalian cleavage factor I Cleavage factor Im complex subunits HDAC1, 2 and 3 form the catalytic subunit of multiprotein complexes to mediate gene transcription although HDAC8 is fully active in isolation. HDAC1 and HDAC2 form the catalytic core of multiple corepressor complexes, including NuRD (nucleosome remodeling and deacetylase), Sin3 (switch intensive 3) CoREST (corepressor of RE1-silencing transcription) and MiDAC (mitotic deacetylase), while HDAC3 forms the key component of the SMRT/NCoR (silencing mediator of retinoic acid and thyroid hormone receptors/nuclear receptor corepressor) complex. As part of these complexes, the HDACs become maximally activated and are targeted to specific regions of chromatin. Histone deacetylase complexes Class I HDAC complexes MiDAC is one of seven distinct, large multi-protein complexes that recruit class I histone deacetylases to the genome to regulate gene expression. mitotic deacetylase complex MiDAC complex subunits A metalloproteinase, or metalloprotease, is any protease enzyme whose catalytic mechanism involves a metal. An example of this would be ADAM12 which plays a significant role in the fusion of muscle cells during embryo development, in a process known as myogenesis. Most metalloproteases require zinc, but some use cobalt. The metal ion is coordinated to the protein via three ligands. The ligands coordinating the metal ion can vary with histidine, glutamate, aspartate, lysine, and arginine. The fourth coordination position is taken up by a labile water molecule. Treatment with chelating agents such as EDTA leads to complete inactivation. EDTA is a metal chelator that removes zinc, which is essential for activity. They are also inhibited by the chelator orthophenanthroline. Metalloproteases Metalloproteinases Metallopeptidases M48 metallopeptidase family M49 metalloprotease family M49 metallopeptidase family M54 metallopeptidase family M76 metallopeptidase family Peptidase family C1 The adenosine receptors (or P1 receptors ) are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand. ADORA P1 receptors Adenosine receptors ADORA VOC members are metalloenzymes highly divergent in sequence and biological functions, but universally share the use of the βαβββ structural motif (also known as the glyoxylase fold) to build a divalent metal-containing active site. VOC enzymes catalyze a range of chemical reactions including isomerization, epimerization, oxidative C-C bond cleavage and nucleophilic substitution Glyoxalase/fosfomycin resistance/dioxygenase domain containing family VOC domain containing superfamily vicinal oxygen chelate domain containing superfamily Glyoxalase domain containing FDX Ferredoxins Ferredoxin family FDX AIMP MSC complex non-enzymatic components Aminoacyl tRNA synthetase complex interacting multifunctional proteins AIMP TPGS Tubulin polyglutamylase complex subunits TPGS LMOD Leiomodins LMOD super killer complex SKI complex subunits Purinergic receptors, also known as purinoceptors, are a family of plasma membrane molecules that are found in almost all mammalian tissues. Broadly, purinergic receptors and signaling have been implicated in learning and memory, locomotor and feeding behavior, and sleep. More specifically, these receptors are involved in several cellular functions, including proliferation and migration of neural stem cells, vascular reactivity, apoptosis and cytokine secretion. These functions have not been well characterized and the effect of the extracellular microenvironment on their function is also poorly understood. The term purinergic receptor was originally introduced to illustrate specific classes of membrane receptors that mediate relaxation of gut smooth muscle as a response to the release of ATP (P2 receptors) or adenosine (P1 receptors). P2 receptors have further been divided into five subclasses: P2X, P2Y, P2Z, P2U, and P2T. To distinguish P2 receptors further, the subclasses have been divided into families of metabotropic (P2Y, P2U, and P2T) and ionotropic receptors (P2X and P2Z). P2R Purinoceptors Purinergic receptors P2R Fc receptors EIF2A kinases EIF2AK EIF2alpha kinases Eukaryotic translation initiation factor 2 alpha kinases EIF2AK Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. There are eight conserved cysteines in Piccolo-type zinc fingers, suggesting that they coordinate two zinc ligands. Piccolo Zn-fingers Zinc fingers, piccolo-type zf-piccolo familiy members Zinc fingers PCLO-type SCF complex core subunits PASD PAS domain containing PASD MIF4G domain containing proteins ML family MD-2 related lipid recognition domain containing P2RY P2Y receptors Purinergic receptors, G-protein coupled P2Y receptors P2RY GIYD GIY-YIG endonuclease domain containing GIYD QIK subfamily SIK SIK family kinases SIK MARK MARK/Par-1/Kin kinases Par-1 family Microtubule affinity regulating kinases MARK AMP-activated protein kinase related kinases AMPK related kinases PRKAA related kinases CAMK-like family AMP-activated protein kinase alpha catalytic subunits PRKAA Protein kinase AMP-activated catalytic subunit alphas PRKAA BRSK Brain selective kinases Brain-specific kinases SAD kinases BR serine/threonine kinases BRSK NUAK NUAK family kinases NUAK MELK MELK family kinases MELK This gene group contains genes that encode proteins with a TRAF-type zinc finger domain. Some of the proteins that have this domain are mammalian signal transducers associated with the cytoplasmic domain of the 75kDa tumour necrosis factor receptor. A heterocomplex, homodimer or heterodimer of TRAF1 and TRAF2, binds to the N-terminal of the inhibitor of apoptosis proteins 1 and 2 (IAPS) and recruits them to the tumour necrosis factor receptor 2. Zinc fingers TRAF-type P2X receptors are a family of cation-permeable ligand gated ion channels that open in response to the binding of extracellular adenosine 5'-triphosphate ( ATP ). They belong to a larger family of receptors known as the purinergic receptors. P2X receptors are present in a diverse array of organisms including humans, mouse, rat, rabbit, chicken, zebrafish, bullfrog, fluke, and amoeba. P2RX P2X purinoreceptors Purinergic receptor P2X, ligand gated ion channels Purinergic receptors, ionotropic Purinergic receptors P2X P2RX PHK Phosphorylase kinase subunits PHK Bridge-like lipid transporter proteins are key regulators of intraorganellar lipid trafficking. The BLTP proteins form physical bridges that span the gap between a donor and a receiver organelle and are are formed by multiple repeats of one motif: a repeating beta groove (RBG), which forms an extremely long semi-open tube with a hydrophobic interior. BLTP Bridge-like lipid transfer protein family BLTP SHMT Serine hydroxymethyltransferase family SHMT In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (EC 2.7.11.11). PKA has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. It should not be confused with 5'-AMP-activated protein kinase (AMP-activated protein kinase). Protein kinase A subunits Phospholipids can be produced by several metabolic routes, and a key reaction that utilizes lysophospholipids and acyl-CoAs as substrates to produce phospholipids is catalyzed by a class of enzymes called lysophospholipid acyltransferases (LPLATs). Based on their primary structures, these LPLATs are divided into two families, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) and the membrane bound O-acyltransferase (MBOAT) families. These two families also contain non-LPLAT members. LPLATs Lysophospholipid acyltransferases Alpha-2-macroglobulin family Opsins are a group of light-sensitive 35–55 kDa membrane-bound G protein-coupled receptors of the retinylidene protein family found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. OPN Opsin receptors OPN Odz family TENM Teneurins Teneurin transmembrane protein family TENM TOX TOX family TOX subfamily of HMG-box proteins thymocyte selection associated high mobility group box family TOX CCC family Electroneutral cation-coupled Cl cotransporter family SLC12 SLC12 family of cation-coupled chloride transporters Solute carrier family 12 SLC12 Metal ion transporter family SLC39 SLC39 family of metal ion transporters Solute carrier family 39 SLC39 High-affinity glutamate and neutral amino acid transporter family SLC1 SLC1 family of amino acid transporters Solute carrier family 1 SLC1 Facilitative GLUT transporter family SLC2 SLC2 family of hexose and sugar alcohol transporters Solute carrier family 2 SLC2 Heavy subunits of the heteromeric amino acid transporters SLC3 SLC3 family Solute carrier family 3 SLC3 Bicarbonate transporter family SLC4 SLC4 family of bicarbonate transporters Solute carrier family 4 SLC4 SLC5 SLC5 family of sodium-dependent glucose transporters Sodium glucose cotransporter family Solute carrier family 5 SLC5 SLC6 SLC6 neurotransmitter transporter family Sodium- and chloride-dependent neurotransmitter transporter family Solute carrier family 6 SLC6 The prokineticin receptor is a G protein-coupled receptor which binds the peptide hormone prokineticin. There are two variants each encoded by a different gene ( PROKR1, PROKR2 ). These receptors mediate gastrointestinal smooth muscle contraction and angiogenesis. PROKR Prokineticin receptors PROKR Cationic amino acid transporter/glycoprotein-associated family SLC7 SLC7 family Solute carrier family 7 SLC7 Na+/Ca2+ exchanger family SLC8 SLC8 family of sodium/calcium exchangers Solute carrier family 8 SLC8 Na+/H+ exchanger family SLC9 SLC9 family of sodium/hydrogen exchangers Solute carrier family 9 SLC9 SLC10 SLC10 family of sodium-bile acid co-transporters Sodium bile salt cotransport family Solute carrier family 10 SLC10 Proton-coupled metal ion transporter family SLC11 SLC11 family of proton-coupled metal ion transporters Solute carrier family 11 SLC11 Human Na+-sulfate/carboxylate cotransporter family SLC13 SLC13 family of sodium-dependent sulphate/carboxylate transporters Solute carrier family 13 SLC13 SLC14 SLC14 family of facilitative urea transporters Urea transporter family Solute carrier family 14 SLC14 Proton oligopeptide cotransporter family SLC15 SLC15 family of peptide transporters Solute carrier family 15 SLC15 Monocarboxylate transporter family SLC16 SLC16 family of monocarboxylate transporters Solute carrier family 16 SLC16 SLC17 SLC17 phosphate and organic anion transporter family Vesicular glutamate transporter family Solute carrier family 17 SLC17 RXFP Relaxin family peptide receptors RXFP SLC18 SLC18 family of vesicular amine transporters Vesicular amine transporter family Solute carrier family 18 SLC18 Folate/thiamine transporter family SLC19 SLC19 family of vitamin transporters Solute carrier family 19 SLC19 SLC20 SLC20 family of sodium-dependent phosphate transporters Type III Na+-phosphate cotransporter family Solute carrier family 20 SLC20 Organic cation/anion/zwitterion transporter family SLC22 SLC22 family of organic cation and anion transporters Solute carrier family 22 SLC22 Na+-dependent ascorbic acid transporter family SLC23 SLC23 family of ascorbic acid transporters Solute carrier family 23 SLC23 Na+/(Ca2+-K+) exchanger family SLC24 SLC24 family of sodium/potassium/calcium exchangers Solute carrier family 24 SLC24 Mitochondrial carrier family SLC25 SLC25 family of mitochondrial transporters Solute carrier family 25 SLC25 Multifunctional anion exchanger family SLC26 SLC26 family of anion exchangers Solute carrier family 26 SLC26 Fatty acid transporter family SLC27 SLC27 family of fatty acid transporters Solute carrier family 27 SLC27 Na+-coupled nucleoside transport family SLC28 SLC28 family Solute carrier family 28 SLC28 CMKLR Resolvin E1 receptor Chemerin receptors CMKLR Facilitative nucleoside transporter family SLC29 SLC29 family Solute carrier family 29 SLC29 SLC30 SLC30 zinc transporter family Zinc efflux family Solute carrier family 30 SLC30 Copper transporter family SLC31 SLC31 family of copper transporters Solute carrier family 31 SLC31 SLC32 SLC32 vesicular inhibitory amino acid transporter Vesicular inhibitory amino acid transporter family Solute carrier family 32 SLC32 Acetyl-CoA transporter family SLC33 SLC33 acetylCoA transporter Solute carrier family 33 SLC33 SLC34 SLC34 family of sodium phosphate co-transporters Type II Na+-phosphate cotransporter family Solute carrier family 34 SLC34 Nucleoside-sugar transporter family SLC35 SLC35 family of nucleotide sugar transporters Solute carrier family 35 SLC35 Proton-coupled amino acid transporter family SLC36 SLC36 family of proton-coupled amino acid transporters Solute carrier family 36 SLC36 SLC38 SLC38 family of sodium-dependent neutral amino acid transporters System A and System N sodium-coupled neutral amino acid transporter family Solute carrier family 38 SLC38 SLC37 SLC37 family of phosphosugar/phosphate exchangers Sugar-phosphate/phosphate exchanger family Solute carrier family 37 SLC37 Protease-activated receptors are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets, but also on endothelial cells, myocytes and neurons. Coagulation factor II (thrombin) receptors F2R PARs Protease-activated receptors Proteinase-activated receptors F2R receptors F2R Basolateral iron transporter family SLC40 SLC40 iron transporter Solute carrier family 40 SLC40 MgtE-like magnesium transporter family SLC41 SLC41 family of divalent cation transporters Solute carrier family 41 SLC41 Rh ammonium transporter family Rh family glycoproteins SLC42 SLC42 family of Rhesus glycoprotein ammonium transporters Solute carrier family 42 SLC42 Na+-independent, system-L-like amino acid transporter family SLC43 SLC43 family of large neutral amino acid transporters Solute carrier family 43 SLC43 Choline-like transporter family SLC44 SLC44 choline transporter-like family Solute carrier family 44 SLC44 H+/sugar cotransporter family SLC45 SLC45 family of putative sugar transporters Solute carrier family 45 SLC45 Folate transporter family SLC46 SLC46 family of folate transporters Solute carrier family 46 SLC46 Multidrug and Toxin Extrusion (MATE) family SLC47 SLC47 family of multidrug and toxin extrusion transporters Solute carrier family 47 SLC47 Heme transporter family SLC48 SLC48 heme transporter Solute carrier family 48 SLC48 FLVCR-related transporter family SLC49 family of FLVCR-related heme transporters SLC49, FLVCR Solute carrier family 49 SLC49, FLVCR A subclass of 'G protein-coupled receptors, Class A rhodopsin-like receptors' that bind peptide ligands via the transmembrane helices and the extracellular loops of the receptor. Peptide receptors SLC50 SLC50 sugar transporter Sugar efflux transporters Solute carrier family 50 SLC50 Riboflavin transporter family SLC52 SLC52 family of riboflavin transporters Solute carrier family 52 SLC52 Phosphate carriers SLC53 SLC53 Phosphate carriers Solute carrier family 53 SLC53 Mitochondrial pyruvate carriers SLC54 Mitochondrial pyruvate carriers SLC54, MPC Solute carrier family 54 Solute carrier family 54, mitochondrial pyruvate carriers SLC54, MPC LETM1 domain containing Mitochondrial cation/proton exchangers SLC55 Mitochondrial cation/proton exchangers SLC55, LETM Solute carrier family 55, LETM mitochondrial cation/proton exchangers SLC55, LETM NiPA-like magnesium transporter family SLC57 NiPA-like magnesium transporter family SLC57, NIPA Solute carrier family 57 Solute carrier family 57, NIPA-like magnesium transporters SLC57, NIPA MagT-like magnesium transporter family Magnesium transporter 1 family SLC58 SLC58 MagT-like magnesium transporter family Solute carrier family 58 SLC58 MFSD2 lysolipid transporter family Major facilitator superfamily domain containing 2 family SLC59 SLC59 Sodium-dependent lysophosphatidylcholine symporter family Sodium-dependent lysophosphatidylcholine symporter family Solute carrier family 59 SLC59 Glucose transporters Major facilitator superfamily domain containing 4 family SLC60 SLC60 Glucose transporters Solute carrier family 60 SLC60 The angiotensin receptors are a class of G protein-coupled receptors with angiotensin II as their ligands. They are important in the renin-angiotensin system : they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II. AGTR Angiotensin receptors AGTR Major facilitator superfamily domain containing 5 family Molybdate transporter family SLC61 SLC61 Molybdate transporter family Solute carrier family 61 SLC61 ANKH inorganic pyrophosphate transport regulator family Pyrophosphate transporters SLC62 Pyrophosphate transporters SLC62, ANKH Solute carrier family 62 SLC62, ANKH SLC63 Sphingosine phosphate transporters SLC63, SPNS Solute carrier family 63 Sphingolipid transporter family Sphingosine-phosphate transporters Spinster homolog gene family Solute carrier family 63, sphingosine phosphate transporters SLC63, SPNS Golgi Ca2+/H+ exchangers SLC64 Golgi Ca2+/H+ exchangers SLC64, TMEM165 Solute carrier family 64 Solute carrier family 64 SLC64, TMEM165 NPC-type cholesterol transporters NPC1 intracellular cholesterol transporter family SLC65 SLC65 NPC-type cholesterol transporters Solute carrier family 65 SLC65 PQ-loop amino acid transporters SLC66 SLC66 Lysosomal amino acid transporters Solute carrier family 66 SLC66 SLC21 family SLCO SLCO family of organic anion transporting polypeptides organic anion transporting polypeptide superfamily Solute carrier organic anion transporter family SLCO DISP Dispatched RND transporter family DISP TMEM14 Transmembrane protein 14 family TMEM14 Bombesin receptors GPI-GnT Complex Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex TUBGCP Tubulin gamma complex component family TUBGCP NHERF Na(+)/H(+) exchange regulatory factors NHERF family PDZ scaffold proteins NHERF TSNAXIP1 domain containing The bradykinin receptor family is a group of G-protein coupled receptors whose principal ligand is the protein bradykinin. There are two Bradykinin receptors: the B 1 receptor and the B 2 receptor. BDKR Bradykinin receptors BDKR YT521-B homology domain containing family YTH YTH domain containing m6A readers YTH domain containing N6-methyladenosine readers YTH THBS Thrombospondins Thrombospondin family THBS ISM Isthmin family ISM MAT MAT catalytic subunits Methionine adenosyltransferase alpha subunits Methionine adenosyltransferase family MAT SAXO Stabilizer of axonemal microtubules family SAXO STAG Stromal antigen family Stromalins STAG family cohesin complex components STAG Cholecystokinin receptors or CCK receptors are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin (CCK) or gastrin. There are two different subtypes CCK A and CCK B which are ~50% homologous : Various cholecystokinin antagonists have been developed and are used in research, although the only drug of this class that has been widely marketed to date is the anti-ulcer drug proglumide. Cholecystokinin receptors Nebulin repeat containing Nebulin family The Gfo/Idh/MocA protein family members have very low sequence identity but the 3D structures of the proteins are very similar, consisting of two main domains: an N-terminal dinucleotide-binding domain containing a typical Rossmann fold3 and a C-terminal α/β-domain participating in substrate binding and oligomerisation. [Note the BLVRA gene included here encodes a protein with the N-terminal, but not C-terminal domain]. Gfo/Idh/MocA-like oxidoreductase domain containing BNC Basonuclins Basonuclin zinc finger proteins BNC PROK Prokineticins Prokineticin family PROK PROM Prominin family PROM Secretory calcium-binding phosphoprotein family The FERRY complex is proposed to function as a Rab5 effector to shuttle mRNA to the cell periphery for local translation. Rab5 effector FERRY complex five-subunit endosomal Rab5 and RNA/ribosome intermediary complex FERRY complex subunits COL Fibril forming collagens Fibrillar collagens COL COL FACIT Fibril associated collagens with interrupted triple helices COL COL Network forming collagens COL EDNR Endothelin receptors EDNR COL MACIT Membrane associated collagens with interrupted triple helices COL COL Transmembrane collagens COL COL Multiple triple-helix domains and interruptions Multiplexins Multiplexin collagens COL EPS8 EPS8 family EPS8 signaling adaptor family EPS8 Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. The flavoproteins are some of the most-studied families of enzymes. Flavoproteins have either FMN (flavin mononucleotide) or FAD (flavin adenine dinucleotide) as a prosthetic group or as a cofactor. The flavin is generally tightly bound (as in adrenodoxin reductase, wherein the FAD is buried deeply). About 5-10% of flavoproteins have a covalently linked FAD. Based on the available structural data, FAD-binding sites can be divided into more than 200 different types.90 flavoproteins are encoded in the human genome; about 84% require FAD and around 16% require FMN, whereas 5 proteins require both. Flavoproteins are mainly located in the mitochondria. Of all flavoproteins, 90% perform redox reactions and the other 10% are transferases, lyases, isomerases, ligases. Flavoproteome Flavoproteins Cdc48-Npl4-Ufd1 complex p97-Nploc4 ATPase complex p97-UFD1-NPL4 unfoldase VCP-Ufd1-Npl4 complex subunits The galanin receptor is a G protein-coupled receptor, or metabotropic receptor which binds galanin. Galanin receptors can be found throughout the peripheral and central nervous systems and the endocrine system. So far three subtypes are known to exist: GAL-R1, GAL-R2, and GAL-R3. The specific function of each subtype remains to be fully elucidated, although as of 2009 great progress is currently being made in this respect with the generation of receptor subtype-specific knockout mice, and the first selective ligands for galanin receptor subtypes. Selective galanin agonists are anticonvulsant, while antagonists produce antidepressant and anxiolytic effects in animals, so either agonist or antagonist ligands for the galanin receptors may be potentially therapeutic compounds in humans. GALR Galanin receptors GALR CERS Ceramide synthases CERS MAF MAF bZIP transcription factor family MAF S-MAF family Small MAF bZIP transcription factor family L-MAF family Large MAF bZIP transcription factor family MFN Mitofusins Mitofusin family MFN NHS NHS family NHS The gonadotropin-releasing hormone receptor (GNRHR), also known as the luteinizing hormone releasing hormone receptor ( LHRHR ), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate. This receptor is a 60 kDa G protein-coupled receptor and resides primarily in the pituitary and is responsible for eliciting the actions of LHRH after its release from the hypothalamus. Upon activation, the LHRHr stimulates tyrosine phosphatase and elicits the release of LH from the pituitary. Evidence exists showing the presence of LHRH and its receptor in extrapituitary tissues as well as a role in progression of some cancers. GNRHR Gonadotropin releasing hormone receptors GNRHR SLC51 SLC51 family of steroid-derived molecule transporters Solute carrier family 51 SLC51 SLC67 SLC67 organic cation transporter-like family Solute carrier family 67 SLC67 SLC68 SLC68 cation symporter family Solute carrier family 68 SLC68 SLC69 Vitamin A receptor/transporter family Solute carrier family 69 SLC69 SLC71 SLC71 putative ammonia transporter family Solute carrier family 71 SLC71 The canonical Notch ligands are members of the Delta/Serrate/Lag-1 (DSL) family of proteins. When they bind to Notch receptors this induces a conformational change (regulated intramembrane proteolysis) in the receptor, freeing its Notch intracellular domain (NICD). The NICD can then translocate to the nucleus and promote gene transcription. DSL ligands Delta/Serrate/lag-2 (DSL) proteins Canonical Notch ligands HCRTR Orexin receptors Hypocretin receptors HCRTR The dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) complex is a protein complex responsible for the regulation of cell cycle-dependent gene expression. The complex is evolutionarily conserved, although some of its components vary from species to species. In humans, the key proteins in the complex are RBL1 (p107) and RBL2 (p130), both of which are homologs of RB (p105) and bind repressive E2F transcription factors E2F4 and E2F5; DP1, DP2 and DP3, dimerization partners of E2F; and MuvB, which is a complex of LIN9/37/52/54 and RBBP4. DREAM complex subunits MuvB complexes are key to regulating the cell-division cycle. The MuvB complex can form part of the transcriptional repressor complex DREAM, or part of the activator complexes MMB and FOXM1-MuvB. When cells are not actively dividing, the DREAM complex represses G1/S and G2/M genes. The expression of mitotic genes in the G2/M stage of the cell cycle can be regulated by MuvB activator complexes which include either the oncogenic transcription factor B-MYB or FOXM1. MuvB complex subunits B-MYB-MuvB complex MuvB:B-MYB complex Myb and MuvB core protein complex Myb-MuvB complex MMB complex subunits MMB-FOXM1 FOXM1-MMB complex subunits This gene group represents genes encoding proteins with the zinc finger domain found in TNFAIP3, also known as A20. TNFAIP3 is an inhibitor of cell death that inhibits NF-kappaB activation via the tumour necrosis factor receptor associated factor pathway. The zinc finger domains appear to mediate self-association in TNFAIP3. These fingers also mediate IL-1-induced NF-kappa B activation. Zinc fingers TNFAIP3-type Zinc fingers A20-type The RNA-binding Fox-1 homolog (RBFOX) proteins represent an ancient family of splicing factors, conserved through evolution. All members share an RNA recognition motif (RRM), and a particular affinity for the GCAUG signature in target RNA molecules. RBFOX RNA-binding Fox-1 homologue (Rbfox) proteins RNA binding fox-1 homologs RBFOX CTR Chymotrypsins CTR Mitochondrial transcription initiation complex subunits Mitochondrial nucleoid associated proteins ELAV like RNA binding proteins ELAVL ELAV like RNA binding protein family ELAVL This group lists protein coding genes that encode a protein that is identical to that encoded by another gene or genes. The list was constructed from a set of UniProt accessions that are associated with multiple genes. The list is limited to genes on the current reference assembly and excludes proteins encoded by read-through transcripts. Genes that encode the same protein share root symbols. Note the H3C root is associated with two different proteins - one encoded by a cluster of genes on 6p22.1 and the other by a cluster of three genes on 1q21.2 (H3C13-15). Proteins encoded by multiple genes LAR family receptor tyrosine phosphatases LAR-RPTPs LAR protein receptor tyrosine phosphatase family Retrotransposable element derived genes Retrotransposon derived genes All genes in this group contain domains that are homologous to retroviral integrase proteins. Domesticated integrase genes Integrase like retrotransposon derived SERCA Transmembrane Peptide Regulatory Subunits SERCA-regulins Regulins TSPY like family TSPYL Testis specific Y-encoded like family TSPYL family TSPYL TSPY TSPY family TSPY NAP1L Nucleosome assembly protein 1 like family NAP1L Nucleosome assembly protein superfamily STOX Storkhead boxes STOX STAC SH3 and cysteine rich domain family STAC SPRED Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology-1 (EVH-1) domain containing family Sprouty-related family Sprouty related EVH1 domain containing SPRED SPRY Sprouty RTK signaling antagonist family SPRY SPRY domain and SOCS box containing family SPSB SplA/ryanodine receptor domain and SOCS box containing family SPSB ZU5 domain containing OLFM Olfactomedin domain containing OLFM NXPH Neurexophilins NXPH NXPE Neurexophilin and PC-esterase domain containing NXPE NXP Neurexophilin domain containing NXP Complexin (also known as synaphin) refers to a one of a small set of eukaryotic cytoplasmic neuronal proteins which binds to the SNARE protein complex (SNAREpin) with a high affinity. These are called synaphin 1 and 2. In the presence of Ca2+, the transport vesicle protein synaptotagmin displaces complexin, allowing the SNARE protein complex to bind the transport vesicle to the presynaptic membrane. Complexin acts as both an inhibitor and a facilitator of synaptic vesicle fusion and neurotransmitter release. In one conformation, it clamps SNAREpin complexes, preventing vesicle fusion, while in a different conformation it releases the SNAREpins, allowing synaptotagmin to trigger fusion. Whereas complexin is not necessary for synaptic vesicle exocytosis, it does increase neurotransmitter release by 60–70% as demonstrated by complexin gene knockout in mice. A number of human neurological diseases have been linked to a deficiency of complexin. Synaphin can promote exocytosis by promoting interaction between the complementary syntaxin and synaptobrevin transmembrane regions that reside in opposing membranes prior to fusion. CPLX Complexins CPLX PCNX Pecanex family PCNX CNPY Canopy FGF signaling regulators CNPY RASGRP RAS guanyl releasing proteins RASGRP Reticulons (RTNs in vertebrates and reticulon-like proteins or RNTls in other eukaryotes) are a group of evolutionary conservative proteins residing predominantly in endoplasmic reticulum, primarily playing a role in promoting membrane curvature. In addition, reticulons may play a role in nuclear pore complex formation, vesicle formation, and other processes yet to be defined. They have also been linked to oligodendrocyte roles in inhibition of neurite outgrowth. Some studies link RTNs with Alzheimer's disease and amyotrophic lateral sclerosis.All eukaryotes studied so far carry RTN genes in their genomes. The reticulons are absent only in archaea and bacteria. Mammals have four reticulon genes, RTN1, RTN2, RTN3, RTN4. Plants possess a greater number of reticulon isoforms, with 21 having been identified in the commonly used model organism Arabidopsis thaliana.The genes possess a number of exons and introns and are accordingly spliced into many isoforms. C-terminal region of RTNs contains a highly conservative reticulon homology domain (RHD) while other parts of the protein may vary even within a single organism.A peculiar feature of RTN4's isoform RTN4A (Nogo-A) is its ability to inhibit axonal growth. This reticulon subform is curiously absent in fish, a taxon known for the heightened ability of its CNS to regenerate after injury. Transmembrane 33 (TMEM33) exogenously suppresses reticulon 4C function and therefore may play a role in dictating membrane curvature through inhibition of reticulon function. RTN Reticulons RTN GARI-L GARIN Golgi associated RAB2 interactor family GARIN LRCH Leucine rich repeats and calponin homology domain containing LRCH CNIH Cornichon family CNIH Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from preexisting blood vessels. Angiogenesis proceeds through sprouting, endothelial cell migration, proliferation, and vessel destabilization and stabilization. They are responsible for assembling and disassembling the endothelial lining of blood vessels. Angiopoietin cytokines are involved with controlling microvascular permeability, vasodilation, and vasoconstriction by signaling smooth muscle cells surrounding vessels. Angiopoietin-1 is critical for vessel maturation, adhesion, migration, and survival. Angiopoietin-2, on the other hand, promotes cell death and disrupts vascularization. Yet, when it is in conjunction with vascular endothelial growth factors, or VEGF, it can promote neo-vascularization. ANG ANGPT Angiopoietins ANGPT LYSMD Lysin motif domain containing LysM domain containing LYSMD disheveled, Egl-10, pleckstrin domain containing DEP domain containing Two Melanin-concentrating hormone receptors ( MCHR ) have recently been characterized: MCH-R1 and MCH-R2. These two receptors share approximately 38% homology. MCHR Melanin concentrating hormone receptors MCHR Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors. There are five known members of the melanocortin receptor system each with differing specificities for melanocortins : MC1R. MC1R is associated with pigmentation genetics. MC2R. MC2R is also known as the ACTH receptor or corticotropin receptor because it is specific for ACTH alone. MC3R. MC3R MC4R. Defects in MC4R are a cause of autosomal dominant obesity, accounting for 6% of all cases of early-onset obesity. MC5R. MC5R These receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti-related peptide, and activated by synthetic (i.e. afamelanotide ) and endogenous agonist melanocyte-stimulating hormones. Melanocortin receptors The neuromedin U receptors are two G-protein coupled receptors which bind the neuropeptide hormones neuromedin U and neuromedin S. There are two subtypes of the neuromedin U receptor, each encoded by a separate gene ( NMUR1, NMUR2 ). NMUR Neuromedin U receptors NMUR The cadherin-related (CDHR) genes do not fit into the major cadherin or protocadherin families as they are phylogenetically clearly separated. The encoded proteins comprise at least two typical, consecutive cadherin motifs, but often more than the typical members of the cadherin and protocadherin families. Their overall domain organization differs from the members of the major cadherin family and the protocadherin family, and includes different and unique cytoplasmic domains. CDHR Cadherin related CDHR The neuropeptide FF receptors are members of the G-protein coupled receptor superfamily of integral membrane proteins which bind the pain modulatory neuropeptides AF and FF. The Neuropeptide FF receptor family is a member of the G protein-coupled receptor superfamily containing two subtypes, NPFF1 and NPFF2, which exhibit a high affinity for Neuropeptide FF (NPFF) peptides. NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density, particularly in mammals in the superficial layers of the spinal cord where it is involved in nociception and modulation of opioid functions These receptors participate to the modulation of opioid receptor function in the brain and spinal cord, and can either reduce or increase opioid receptor function depending which tissue they are released in, reflecting a complex role for neuropeptide FF in pain responses. NPFFR Neuropeptide FF/neuropeptide AF receptors Neuropeptide FF receptors NPFFR The neuropeptide S receptor ( NPSR ) is a member of the G-protein coupled receptor superfamily of integral membrane proteins which binds neuropeptide S (NPS). It was formerly an orphan receptor, GPR154, until the discovery of neuropeptide S as the endogenous ligand. In the CNS, activation of the NPSR by NPS promotes arousal and anxiolytic -like effects. In addition, mututations in NPSR have been linked to a susceptibility to asthma. Hence NPSR has also been called GPRA (G protein-coupled receptor for asthma susceptibility). Activation of NPSR in the airway epithelium has a number of effects including upregulation of matrix metalloproteinases which are involved in the pathogenesis of asthma. This gene is a member of the G protein-coupled receptor 1 family and encodes a plasma membrane protein. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Mutations in this gene have also been associated with this disease. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. NPSR Neuropeptide S receptor NPSR NPBWR Neuropeptide W/neuropeptide B receptors Neuropeptides B and W receptors NPBWR Neuropeptide Y receptors are a class of G-protein coupled receptors which are activated by the closely related peptide hormones neuropeptide Y, peptide YY and pancreatic polypeptide. These receptors are involved in the control of a diverse set of behavioral processes including appetite, circadian rhythm, and anxiety. Activated neuropeptide receptors release the G i subunit from the heterotrimeric G protein complex. The G i subunit in turn inhibits the production of the second messenger cAMP from ATP. Neuropeptide Y receptors NTSR Neurotensin receptors NTSR Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). Opiate receptors are distributed widely in the brain, and are found in the spinal cord and digestive tract. OPR Opioid receptors OPR This small family of 2 members putatively forms cation-selective ion channels. They are predicted to contain two KV-style six-transmembrane domains, suggesting they form a dimer in the membrane. These channels are closely related to CatSper channels and, more distantly, to TRP channels. TPCN Two pore channels Two-pore channels Two pore segment channels TPCN Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other. These are grouped into two broad groups: Group 1 includes TRPC ( 'C' for canonical), TRPV ('V' for vanilloid), TRPM ('M' for melastatin), TRPN, and TRPA. In group 2, there are TRPP ('P' for polycystic) and TRPML ('ML' for mucolipin). Many of these channels mediate a variety of sensations like the sensations of pain, hotness, warmth or coldness, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic ( allicin ), chilli pepper ( capsaicin ), wasabi ( allyl isothiocyanate ); others are activated by menthol, camphor, peppermint, and cooling agents; yet others are activated by molecules found in cannabis (i.e., THC, CBD and CBN ). Some act as sensors of osmotic pressure, volume, stretch, and vibration. These ion channels are relatively non-selectively permeable to cations, including sodium, calcium and magnesium. TRP channels were initially discovered in trp -mutant strain of the fruit fly Drosophila. Later, TRP channels were found in vertebrates where they are ubiquitously expressed in many cell types and tissues. Most TRP channels are composed of 6 membrane -spanning helices with intracellular N- and C-termini. Mammalian TRP channels are activated and regulated by a wide variety of stimuli and are expressed throughout the body. TRP Transient receptor potential cation channels TRP Cyclic nucleotide-gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. Their function can be the result of a combination of the binding of cyclic nucleotides (cGMP and cAMP) and either a depolarization or a hyperpolarization event. Initially discovered in the cells that make up the retina of the eye, CNG channels have been found in many different cell types across both the animal and the plant kingdoms. CNG channels have a very complex structure with various subunits and domains that play a critical role in their function. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis. CNG CNG channels Cyclic nucleotide-gated ion channels Cyclic nucleotide gated channels CNG Voltage-dependent calcium channels ( VDCC ) are a group of voltage-gated ion channels found in the membrane of excitable cells ( e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca 2+. These channels are slightly permeable to sodium ions, so they are also called Ca 2+ -Na + channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VDCCs are normally closed. They are activated ( i.e., opened) at depolarized membrane potentials and this is the source of the 'voltage-dependent' epithet. The concentration of calcium (Ca 2+ ions) is normally several thousand times higher outside of the cell than inside. Activation of particular VDCCs allows Ca 2+ to rush into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, excitation of neurons, up-regulation of gene expression, or release of hormones or neurotransmitters. Excessive activation of VDCCs is a major component of excitotoxicity, as severely elevated levels of intracellular calcium activates enzymes which, at high enough levels, can degrade essential cellular structures. CACN Calcium channels, voltage-dependent VDCC Voltage-dependent calcium channels Voltage-dependent l-type calcium channels Calcium voltage-gated channel subunits CACN HVCN Hydrogen voltage-gated channels Proton channels Hydrogen voltage gated channels HVCN Calcium-activated potassium channels are divided into BK [KCNMA1] channels, IK [KCNN4] channels, and SK [KCNN1-3] channels based on their conductance (big, intermediate, and small conductance). Calcium-activated potassium channels KCa Potassium channels, calcium-activated Potassium calcium-activated channels SSTR Somatostatin receptors SSTR There are three known mammalian tachykinin receptors. All are members of the 7 transmembrane G-protein coupled receptor family and induce the activation of phospholipase C, producing inositol triphosphate (so called G q-coupled). TACR Tachykinin receptors TACR The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into V1, V2 and V3 subtypes. These three subtypes differ in localization, function and signal transduction mechanisms. AVPR Vasopressin receptors Arginine vasopressin and oxytocin receptors AVPR A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions in order to stabilize the fold. Originally coined to describe the finger-like appearance of a hypothesized structure from Xenopus laevis transcription factor IIIA, the zinc finger name has now come to encompass a wide variety of differing protein structures. Proteins that contain zinc fingers ( zinc finger proteins ) are classified into several different structural families. Unlike many other clearly defined supersecondary structures such as Greek keys or beta hairpins, there are a number of unique types of zinc fingers, each with a unique three-dimensional architecture. A particular zinc finger protein's class is determined by this three-dimensional structure, but it can also be recognized based on the primary structure of the protein or the identity of the ligands coordinating the zinc ion. In spite of the large variety of these proteins, however, the vast majority typically function as interaction modules that bind DNA, RNA, proteins, or other small, useful molecules, and variations in structure serve primarily to alter the binding specificity of a particular protein. Since their original discovery and the elucidation of their structure, these interaction modules have proven ubiquitous in the biological world. In addition, zinc fingers have become extremely useful in various therapeutic and research capacities. Engineering zinc fingers to have an affinity for a specific sequence is an area of active research, and zinc finger nucleases and zinc finger transcription factors are two of the most important applications of this to be realized to date. Zinc fingers This set contains class A 'orphan' G protein coupled receptors where the endogenous ligand(s) is not known. GPCR class A orphans G protein-coupled receptors, Class A orphans G protein-coupled receptors, Class B secretin-like VIP and PACAP receptors Vasoactive intestinal peptide family receptors The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism. CT works by activating the G-proteins G s and G q often found on osteoclasts, on cells in the kidney, and on cells in a number of regions of the brain. It may also affect the ovaries in women and the testes in men. The function of the CT receptor protein is modified through its interaction with Receptor activity-modifying proteins (RAMPs), forming the multimeric amylin receptors AMY 1 (CT + RAMP1), AMY 2 (CT + RAMP2), and AMY 3 (CT+ RAMP3). CALCR Calcitonin receptors CALCR CRHR Corticotropin releasing factor receptors Corticotropin releasing hormone receptors CRHR Glucagon receptor family ANP32 ANP32 acidic nuclear phosphoproteins ANP32 There are two known parathyroid hormone receptors in mammals termed PTH1R and PTH2R. These receptors bind parathyroid hormone and are members of the GPCR family of transmembrane proteins. parathyroid hormone 1 receptor (PTH1R) is the classical PTH receptor, is expressed in high levels in bone and kidney and regulates calcium ion homeostasis through activation of adenylate cyclase and phospholipase C. parathyroid hormone 2 receptor (PTH2R) is expressed primarily in the central nervous system, pancreas, testis, and placenta. Parathyroid hormone receptors Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state. Kv Potassium voltage-gated channels The class C G-protein-coupled receptors (IPR000337) are a class of G-protein coupled receptors that include the metabotropic glutamate receptors (IPR000162) and several additional receptors. Family C GPCRs have a large extracellular N-terminus which binds the orthosteric (endogenous) ligand. The shape of this domain is often likened to a clam. Several allosteric ligands to these receptors have been identified and these bind within the seven transmembrane region. G protein-coupled receptors, Class C metabotropic glutamate/pheromone Inwardly rectifying potassium channels ( Kir, IRK ) are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types and they are also found in plants. They are the targets of multiple toxins, and malfunction of the channels has been implicated in several diseases. IRK Inward-rectifier potassium ion channels Inwardly-rectifying potassium channels KCNJ Kir Potassium channels, inwardly rectifying subfamily J Potassium inwardly rectifying channel subfamily J KCNJ The two-pore-domain potassium channel a family of 15 members form what is known as 'leak channels' which possess Goldman-Hodgkin-Katz (open) rectification. These channels are regulated by several mechanisms including oxygen tension, pH, mechanical stretch, and G-proteins. Their name is derived from the fact that the alpha subunits consist of four transmembrane segments, each containing two pore loops. As such, they structurally correspond to two inward-rectifier alpha subunits and thus form dimers in the membrane. K2p KCNK Potassium channel, two pore domain subfamily K Potassium selective leak channels Tandem of P domains in a weak inward rectifying K+ channel family Tandem pore domain potassium channels Two-P potassium channels Potassium two pore domain channel subfamily K KCNK Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members. Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups. The importance of one such group, the CLC family of chloride channels, can be seen from the diseases that develop when the channel does not function normally. This family of ion channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three CLC subfamilies are found in animals. CLC-1 ( P35523 ) is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. These proteins contain two CBS domains. Chloride channels are also important for maintaining safe ion concentrations within plant cells. Chloride channels The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone (PTH). Calcium sensing receptors The Cys2His2-like fold group is by far the best-characterized class of zinc fingers and are extremely common in mammalian transcription factors. These domains adopt a simple ββα fold and have the amino acid Sequence motif: X2-Cys-X2,4-Cys-X12-His-X3,4,5-His Cys2His2-like fold containing ZNF zf-C2H2 Zinc fingers C2H2-type ZNF GABA B receptors (GABA BR) are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA) that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential the GABA B-mediated IPSP is -100 mV, which is much more hyperpolarized than the GABA A IPSP. GABA B receptors are found in the central and peripheral autonomic nervous system. GABA BRs GABA(B) receptors GABBR Gamma-aminobutyric acid (GABA) B receptors Gamma-aminobutyric acid type B receptor subunits GABBR The metabotropic glutamate receptors, or mGluR s, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter. GRM Glutamate receptors, metabotropic Metabotropic glutamate receptors mGluR Glutamate metabotropic receptors GRM Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate (glutamic acid) is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation. Glutamate receptors are implicated in a number of neurological conditions. Their central role in excitotoxicity and prevalence in the central nervous system has been linked or speculated to be linked to many neurodegenerative diseases, and several other conditions have been further linked to glutamate receptor gene mutations or receptor autoantigen /antibody activity. Glutamate receptors NALCN Sodium leak channels, non selective NALCN The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are four classes of ionotropic glutamate receptors, namely NMDA receptor, AMPA receptor, Delta receptor and kainate receptors. They are believed to play critical roles in synaptic plasticity. At many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors and kainate receptors can act as the induction trigger for long-term changes in synaptic transmission. GRI Glutamate receptors, ionotropic Ionotropic glutamate receptors iGluR Glutamate ionotropic receptors GRI This set contains class C 'orphan' G protein coupled receptors where the endogenous ligand(s) is not known. G protein-coupled receptors, Class C orphans Frizzled is a family of G protein-coupled receptor proteins that serve as receptors in the Wnt signaling pathway and other signaling pathways. FZD Frizzled receptors G protein-coupled receptors, Class F frizzled FZD Ryanodine receptors ( RyRs ) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. It is the major cellular mediator of calcium-induced calcium release (CICR) in animal cells. RYR Ryanodine receptors RYR Pannexins (from Greek 'pan' all, and from Latin 'nexus' connection) are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane channels connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments (such as ATP and sulforhodamine B). PANX Pannexins PANX A taste receptor is a type of receptor which facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locations. Molecules which give a sensation of taste are considered 'sapid'. Taste receptors Acid-Sensing Ion Channels (ASICs) are neuronal voltage-insensitive cationic channels activated by extracellular protons. ASIC proteins are a subfamily of the ENaC/Deg superfamily of ion channels. To date five proteins of the ASIC family have been identified that arise from four genes, ASIC1, ASIC2, ASIC3, and ASIC4. ASIC1a, 1b and 2a, 2b are splice variants. ASICs are trimeric and can be made up of different combinations of subunits. ASIC2b is non functional on its own but modulates channel activity when participating in heteromultimers. ASIC4 has no known function. All ASICs are expressed in the peripheral nervous system while ASIC1a, 2a, 2b and 4 are expressed in the central nervous system. ASICs are Na+ permeable with ASIC1a showing low Ca++ permeability. ASIC Acid sensing (proton gated) ion channels Acid sensing ion channels Acid-Sensing Ion Channels Acid-sensing (proton-gated) ion channels Acid sensing ion channel subunits ASIC Pheromones have evolved in all animal phyla, to signal sex and dominance status, and are responsible for stereotypical social and sexual behaviour among members of the same species. In mammals, these chemical signals are believed to be detected primarily by the vomeronasal organ (VNO), a chemosensory organ located at the base of the nasal septum. The VNO is present in most amphibia, reptiles and non-primate mammals but is absent in birds, adult catarrhine monkeys and apes. An active role for the human VNO in the detection of pheromones is disputed; the VNO is clearly present in the fetus but appears to be atrophied or absent in adults. Three distinct families of putative pheromone receptors have been identified in the vomeronasal organ (V1Rs, V2Rs and V3Rs). All are G protein-coupled receptors but are only distantly related to the receptors of the main olfactory system, highlighting their different role. The V1 receptors share between 50 and 90% sequence identity but have little similarity to other families of G protein-coupled receptors. They appear to be distantly related to the mammalian T2R bitter taste receptors and the rhodopsin-like GPCRs. A number of human V1 receptor homologues have also been found. The majority of these human sequences are pseudogenes but an apparently functional receptor has been identified that is expressed in the human olfactory system. VN1R, VN2R Vomeronasal receptors VN1R, VN2R Ion channels by channel type Similar to G protein-coupled receptors (GPCRs), ADIPOR1 also possesses 7 transmembrane domains. However ADIPOR1 is orientated oppositely to GPCRs in the membrane (i.e., cytoplasmic N-terminus, extracellular C-terminus) and does not associate with G proteins. ADIPOR Adiponectin receptors ADIPOR Ion channels by gating mechanism Inositol trisphosphate receptor ( InsP3R ) is a membrane glycoprotein complex acting as a Ca 2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca 2+ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca 2+ signals characterized by complex patterns relative to both space and time. For example, Ca 2+ waves and oscillations. The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine. ITPR Inositol triphosphate receptors InsP3R Inositol 1,4,5-triphosphate receptors ITPR FSCN Fascins Fascin family FSCN Chloride channels, calcium activated Chloride calcium-activated channels CLCN Chloride channels, voltage-sensitive Chloride voltage-gated channels CLCN Membrane protein which in a multimeric form constitutes a water-filled transmembrane channel (a pore). This pore allows the passage of ions and numerous other, non-specific molecules through the membrane. Found in the mitochondrial and plastid outer membrane of eukaryotes, in many Gram-negative bacteria, at least some Corynebacterineae, archaea and in sea anemones. Porin channels Water and solutes channels Porins Aquaporins are integral membrane proteins from a larger family of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. Genetic defects involving aquaporin genes have been associated with several human diseases. The 2003 Nobel Prize in Chemistry was awarded jointly to Peter Agre for the discovery of aquaporins, and Roderick MacKinnon for his work on the structure and mechanism of potassium channels. The plasma membranes of a variety of different animal and plant cells contain aquaporins through which water can flow more rapidly inside the cell than by diffusing through the phospholipid bilayer. AQP Aquaporins AQP Voltage-dependent anion channels are a class of porin ion channel located on the outer mitochondrial membrane. There is debate as to whether or not this channel is expressed in the cell surface membrane. This major protein of the outer mitochondrial membrane of eukaryotes forms a voltage-dependent anion-selective channel (VDAC) that behaves as a general diffusion pore for small hydrophilic molecules. The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. VDAC facilitates the exchange of ions and molecules between mitochondria and cytosol and is regulated by the interactions with other proteins and small molecules. VDAC Voltage dependent anion channels VDAC CLIC CLIC family Chloride intracellular channels CLIC CFTR Chloride channels, ATP-gated CFTR CFTR These genes encode proteins that are predicted to encode seven transmembrane regions, but they do not fall into any specific class of G protein-coupled receptor and ligands for the putative 'receptors' have not been identified. 7TM uncharacterized proteins Connexins, or gap junction proteins, are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions (an entirely different family of proteins, the innexins, form gap junctions in invertebrates). Each gap junction is composed of two hemichannels, or connexons, which are themselves each constructed out of six connexin molecules. Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. For this reason, mutations in connexin-encoding genes can lead to functional and developmental abnormalities. Connexins GJ Gap junction proteins GJ Receptor kinases Receptor tyrosine kinases (RTKs), a family of cell-surface receptors, which transduce signals to polypeptide and protein hormones, cytokines and growth factors are key regulators of critical cellular processes, such as proliferation and differentiation, cell survival and metabolism, cell migration and cell cycle control. In the human genome, 58 RTKs have been identified, which fall into 20 families. All RTKs display an extracellular ligand binding domain, a single transmembrane helix, a cytoplasmic region containing the protein tyrosine kinase activity (occasionally split into two domains by an insertion, termed the kinase insertion), with juxta-membrane and C-terminal regulatory regions. Agonist binding to the extracellular domain evokes dimerization, and sometimes oligomerization, of RTKs (a small subset of RTKs forms multimers even in the absence of activating ligand). This leads to autophosphorylation in the tyrosine kinase domain in a trans orientation, serving as a site of assembly of protein complexes and stimulation of multiple signal transduction pathways, including phospholipase C-γ, mitogen-activated protein kinases and phosphatidylinositol 3-kinase. RTKs Receptor tyrosine kinases DEXD DexD/H helicases DEXD The CERF complex has intrinsic nucleosome-dependent ATPase activity and remodels chromatin in an ATP-dependent fashion. CERF (CECR2-containing-remodeling factor) complex CERF chromatin remodelling complex CERF complex ISWI complexes contain the product of either SMARCA1 or SMARCA5, co-orthologs of the S. cerevisiae genes ISWI1 and ISWI2, with one or more regulatory subunit(s). ISWI complexes An ATP-dependent chromatin remodeling complex, that regulates the even spacing of nucleosomes along the chromatin thus promoting chromatin assembly and the repression of transcription. The BAZ1A subunit can enhance and direct the process provided by the ATPase subunit, SMARCA5, probably through targeting pericentromeric heterochromatin in late S phase. Moves end-positioned nucleosomes to a predominantly central position. The ATPase activity of the complex is regulated by the length of flanking DNA. Also involved in facilitating the DNA replication process. ACF complex Chromatin remodeling complex required for maintaining chromatin structure by regulating the spacing of nuclesomes during replication. It is recruited to the replication foci through a direct interaction between the BAZ1B subunit and the DNA clamp PCNA. It opens up chromatin after nucleosome assembly upstream of the replication fork and prevents aberrant heterochromatin formation shortly after DNA replication. The BAZ1B subunit phosphorylates H2A.X Tyr-142 regulating the H2A.X DNA damage response. Particularly important during embryonic and neonatal development, especially for craniofacial features. WSTF-ISWI chromatin remodeling complex WICH complex NoRC remodels nucleosomes at the rDNA promoter and recruits histone deacetylases, histone methyltransferase and DNA methyltransferases leading to heterochromatin formation and transcriptional silencing. The interaction of NoRC with the short RNA transcripts is mediated by the TAM domain of BAZ2A and it is required for NoRC binding to chromatin and heterochromatin formation. Nucleolar remodeling complex NoRC complex A nucleosome remodeling complex that participates in chromatin assembly and facilitates DNA transcription. The RSF1 subunit functions as the histone chaperone through an association with the H3/H4 tetramer and is independent of the histone tails. The histone octamer (composed of H2A, H2B, H3 & H4) is required for the RSF complex to bind DNA. The SMARCA5 subunit provides the energy for the nucleosome spacing activity and is dependent on the histone tails. RSF complex ATP dependent remodeling complexes mobilize nucleosomes along DNA, promote the exchange of histones, or completely displace nucleosomes from DNA. These remodeling complexes are often categorized based on the domain organization of their catalytic subunit. ATP-dependent chromatin remodeling complexes The CHHC U11-48K-type zinc finger contains four invariant Cys and His residues with a consensus sequence of C-x(5,7)-H-x(7,9)-H-x(3,4)-C. It stochiometrically binds zinc ions in a one-to-one ratio. The structure of the CHHC U11-48K-type zinc finger consists of a β hairpin followed by a helix. the zinc ion is coordinated by Cys and His residues from the β hairpin and by His and Cys residues from the helix, respectively. The helical region has an α-helical conformation that is interrupted in the middle by a single pi-helical turn (<a href='https://pubmed.ncbi.nlm.nih.gov/19217400/'>PMID:19217400</a>). CHHC U11-48K-type zinc fingers TRM13/UPF0224 family, U11-48K-like CHHC zinc finger domain Zinc fingers U11-48K-like CHHC-type Methyltransferase families grouped by structure Methyltransferase families grouped by substrate Homocysteine domain containing methyltransferases Membrane-bound methyltransferases Precorrin-like methyltransferase family Tetrapyrrole methylase domain containing tRNA wybutosine-synthesizing protein domain containing MFSD1 family SLC72 SLC72 lysosomal solute carrier family Solute carrier family 72 SLC72 MFSD6 transporter family SLC73 Solute carrier family 73 SLC73 Lysosomal chloride channel family MFSD8 family SLC74 SLC74 lysosomal chloride channel family Solute carrier family 74 SLC74 SLC75 SLC75 tetracycline transporter-like family Solute carrier family 75 SLC75 RFT1 family SLC76 SLC76 glycolipid translocator family Solute carrier family 76 SLC76 7BS N3-cytosine RNA methyltransferases 7BS N1-adenosine RNA methyltransferases 7BS N2-guanosine RNA methyltransferases 7BS N7-guanosine RNA methyltransferases 7BS C5-uridine RNA methyltransferases This group is currently identical to the 7BS protein arginine methyltransferases Arginine n-methyltransferases Arginine methyltransferases 7BS protein histidine methyltransferases Histidine methyltransferases Glutamine methyltransferases Protein methyltransferases DNA/RNA methyltransferases Small molecule methyltransferases Ribonuclease P (RNase P) is an important ribonucleoprotein (RNP), responsible for the maturation of the 5' end of precursor tRNAs (pre-tRNAs). Nuclear ribonuclease P Nuclear RNase P complex subunits Human RNase MRP is a ribonucleoprotein (RNP) enzyme that processes precursor rRNA (pre-rRNA) at ITS1 site 2 and may have additional activities. Mitochondrial RNA processing ribonuclease RNase MRP complex subunits RNase P complexes Bromodomain and WD repeat domain containing Non-histone lysine methyltransferases N- and C-terminal methyltransferases Isoaspartate methyltransferases The aurora kinases (AURKs) comprise an evolutionarily conserved family of serine/threonine kinases involved in mitosis and meiosis. AURK Aur family Aurora kinase family AURK The Polo like kinases are a family of serine/threonine kinases characterized by the presence of an N-terminal protein kinase domain and a C-terminal polo-box domain (PBD) involved in substrate binding and regulation of kinase activity. The truncated protein kinase domain in PLK5 is predicted to be catalytically inactive but the protein retains important functions in neuron biology. PLK PLK family Polo like kinase family PLK The Pim kinases are a family of constitutively active serine/threonine kinases, widely associated with cell survival, proliferation, and migration. PIM Pim proto-oncogene family PIM kinase family PIM Members of the FET protein family, consisting of FUS, EWSR1, and TAF15, bind to RNA and contribute to the control of transcription, RNA processing, and the cytoplasmic fates of messenger RNAs in metazoa. FET proteins can also bind DNA, which may be important in transcription and DNA damage responses. FET proteins are of medical interest because chromosomal rearrangements of their genes promote various sarcomas and because point mutations in FUS or TAF15 can cause neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar dementia. FUS/EWS/TAF15 Protein Family FET protein family The Tribbles (TRIB) family of serine/threonine pseudokinases function as important signalling mediators and scaffold subunits via the binding and modulation of several signalling molecules, including kinases, phosphatases, transcription factors and components of the ubiquitin–proteasome system. TRIB Trbl family Tribbles pseudokinase family TRIB This group represents genes that are named as unitary pseudogenes. Unitary pseudogenes are a type of pseudogene that arises from the loss of function, rather than duplication or retrotransposition. These pseudogenes lack a functioning parent gene in the genome but have functional orthologs. Unitary pseudogenes The PEAK family of pseudokinase scaffolds are important regulators and integrators of cellular signaling and also play oncogenic roles in a variety of human cancers. PEAK PEAK pseudokinase family PEAK The NIMA family of serine/threonine kinases is a diverse group of protein kinases implicated in a wide variety of cellular processes, including cilia regulation, microtubule dynamics, mitotic processes, cell growth, and DNA damage response. NEK NIMA related kinase family NEK Containing CDK, MAPK, GSK3, CLK families CMGC kinase families The Glycogen synthase kinase 3 family are constitutively active multi-functional serine/threonine kinases that are involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. GSK subfamily GSK3 Glycogen synthase kinase 3 family GSK3 Rad2/XPG endonuclease family PIN-like domain superfamily LPEAT 1-acylglycerophosphoethanolamine O-acyltransferases LPEAT Multicopper ferroxidase family Cupredoxin superfamily Multicopper oxidase family Hexokinases phosphorylate a variety of hexose sugars, although their preferred substrate is glucose. GCK has a single hexokinase domain while the other family members have two hexokinase domains but only HK2 has been shown to have two active sites. HK Hexokinase family HK Membrane bound guanylyl cyclases include an external ligand-binding domain (e.g., for peptide hormones such as BNP and ANP), a transmembrane domain, and an internal catalytic domain homologous to adenylate cyclases. GUCY2 Membrane bound guanylyl cyclases Membrane-bound guanylate cyclases RGC family Receptor Guanylate Cyclase family Transmembrane guanylyl cyclases Type I membrane-bound GC-linked receptors Transmembrane guanylate cyclases GUCY2 Caspase-2-driven apoptosis is elicited in blood cells failing cytokinesis and extra centrosomes are necessary to trigger this cell death. Activation of caspase-2 depends on the PIDDosome multi-protein complex, and priming of PIDD1 at extra centrosomes is necessary for pathway activation CASP2-PIDDosome Caspase-2 PIDDosome complex Cholinesterases may be classified as acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) on the basis of differential specificity for acetylcholine and butyrylcholine hydrolysis. Several inhibitors have also been shown to be selective for one of the two enzymes. AChEs are primarily associated with nerve and muscle, typically with localization at synaptic contacts, while BChE is synthesized in the liver with substantial amounts appearing in serum. Cholinesterases Cholinesterase family Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Within the holoenzyme, PCCA catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, while PCCB then transfers the carboxyl group from carboxylated biotin to propionyl-CoA. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia. PCC Propionyl-CoA carboxylase Propionyl-CoA carboxylase subunits PCC Acetyl-coenzyme A carboxylases (commonly called ACCs) have crucial roles in fatty acid metabolism in most living organisms. Acetyl-coenzyme A carboxylase is a biotin-dependent enzyme and catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). It is a multi-subunit enzyme in most prokaryotes, whereas it is a large, multi-domain enzyme in most eukaryotes. ACAC Acetyl-CoA carboxylases Acetyl-CoA carboxylase family ACAC A reverse transcriptase complex that is essential for maintenance of telomeres. Catalytic subunit TERT and RNA template TERC are essential for telomerase activity, adding telomeric repeats (TTAGGG) at chromosome ends to compensate for the telomere loss that is caused by incomplete genome end replication Elongates the single-stranded G-rich 3' protruding ends of chromosomal DNA using TERC RNA as a template. WRAP53 (also known as TCAB1) binds to the CAB box in TERC and facilitates localization of the telomerase complex to Cajal bodies. In S-phase, telomerase holoenzyme complex is targeted from Cajal bodies to telomeres by binding of TERT to the shelterin subunit, ACD. Telomerase holoenzyme subunits The RIGI family of RNA sensors are pattern recognition receptors that recognize pathogen RNA and trigger an innate immune response. RIG-I-like receptors RLRs retinoic acid-inducible gene-I (RIG-I)-like receptors RIG-I RNA sensor family RSTK RSTK family Receptor serine/threonine kinase family RSTK Prostaglandin-endoperoxide synthases catalyze the committed step in prostaglandin synthesis and act both as a cyclooxygenases and peroxidases. Cyclooxygenases PTGS Prostaglandin G/H synthase and cyclooxygenase family Prostaglandin-endoperoxide synthase family PTGS CDC7 encodes a conserved serine/threonine kinase that serves as a critical regulator of origin firing during DNA replication. CDC7 CDC7 kinase family CDC7 Pyruvate carboxylase (PC) is a nuclear encoded mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate. PC is a biotinylated homotetramer that contains three major regions encompassing the biotin-carboxylase, transcarboxylation, and biotin-binding domains. PC Pyruvate carboxylase family PC Biotin-dependent carboxylases have two distinct enzymatic activities and catalyze their reactions in two steps. First, a biotin carboxylase (BC) component catalyzes the MgATP-dependent carboxylation of the N1′ atom of the biotin cofactor, using bicarbonate as the CO2 donor. Biotin is covalently linked through an amide bond to a lysine side chain in the biotin carboxyl carrier protein (BCCP) component. In the second step of the reaction, a carboxyltransferase (CT) component catalyzes the CO2 transfer from carboxybiotin to the acceptor of the carboxyl group. Depending on the organism and the enzyme, the components can be separate subunits or part of a multi-domain protein. Biotin-dependent carboxylases The homeodomain interacting protein kinases are a family of nuclear dual-specificity serine/threonine and tyrosine kinases that belong to the CMGC superfamily of protein kinases. HIPKs act as transcriptional regulators and corepressors for homeodomain transcription factors and regulate a diverse range of cellular functions, including cytokinesis and apoptosis, ultimately playing roles in adipogenesis, tumor suppression, angiogenesis, and inflammation. Based on similarity of the kinase domain sequence, HIPK kinases are most closely related to DYRK kinases. Three of four HIPK protein kinases in humans, HIPK1, HIPK2, HIPK3, and HIPK4, share a common domain architecture. HIPK1–3 consist of a highly conserved N-terminal kinase domain and several C-terminal regulatory domains including the homeoprotein-interacting domain (HID). HIPK4 stands out as a unique family member because it consists of only a kinase domain. HIPK HIPK family kinases Homeodomain interacting protein kinase family HIPK The doublecortin-like kinases (DCLKs) are members of the calcium/calmodulin-dependent kinase (CAMK) clade of serine/threonine kinases. DCLK proteins contain N-terminal doublecortin-like (DCX) domains, microtubule-binding elements that play a role in microtubule dynamics, neurogenesis, and neuronal migration. DCAMKL family DCLK DCLK family Doublecortin like kinase family DCLK Protein kinase D is encoded by a family of three closely related genes (PRKD1-3). PRKDs are members of the calcium/calmodulin-dependent kinase (CAMK) clade of serine/threonine kinases. PKD family PRKD PRKD family Protein kinase D family PRKD The protein serine kinase H family are members of the calcium/calmodulin-dependent kinase (CAMK) clade of serine/threonine kinases. PSKH1 is an active kinase with a crucial role in kidney development. PSKH2 is closely related to PSKH1 but has an Asn rather than Asp residue at the active site and is likely to be a pseudokinase. PSK family PSKH PSKH family Protein serine kinase H family PSKH ALKs Type I receptor serine/threonine kinases activin receptor-like kinases Type 1 receptor serine/threonine kinases The testis specific serine kinase family are members of the calcium/calmodulin-dependent kinase (CAMK) clade of serine/threonine kinases. TSSK TSSK family Testis specific serine kinase family TSSK Sperm-specific cation channel, CatSper mediated Ca2+ signalling initiates the tyrosine phosphorylation cascade thereby controlling sperm motility. Also plays a central role in sperm chemotaxis, and mediates the Ca2+ influx induced by the steroid sex hormone progesterone in human sperm. Defective CatSper function affects migration, possibly preventing sperm reaching the site of fertilization, thereby displaying an infertility phenotype in mice and humans. Deletions of CatSper2 and CatSper epsilon variants c.2394_2399del are associated with CatSper-related male infertility. Complex contains the largest number of subunits of any known ion channel with CatSper1-4 conforming to the canonical domain-swapped voltage-gated ion channel fold in a counterclockwise direction, while the auxiliary subunits CatSper-beta, gamma, delta and epsilon exist in a pavilion-like structure that stabilizes the entire complex through interactions with CatSper4, 1, 3 and 2 respectively. Sperm cation channel complex CatSpermasome complex Checkpoint kinase 1 (CHEK1) is a serine/threonine kinase required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. CHEK1 belongs to the PRKAA related kinase group; it has no paralogs and is placed in its own subfamily. CHEK1 CHK1 subfamily Checkpoint kinase 1 family CHEK1 The 3M complex maintains microtubule and genome integrity. OBSL1 and CCDC8 form a complex with CUL7 and regulate the level and centrosomal localization of CUL7, respectively. 3M E3 ubiquitin ligase complex CUL7-OBSL1-CCDC8 complex 3M complex subunits Inosine-5′-monophosphate dehydrogenase (IMPDH) is an essential enzyme in purine biosynthesis where it catalyzes the first committed step in GTP synthesis. In humans, there are two isoforms of IMPDH that share 84% sequence identity: IMPDH2 is up-regulated in proliferating cells while IMPDH1 plays a housekeeping role and is expressed in most tissues. Missense mutations in both genes lead to disease in humans. Mutations in IMPDH1 result in autosomal dominant blindness in the form of retinitis pigmentosa (RP) or Leber congenital amaurosis (LCA). Mutations in IMPDH2 are associated with severe juvenile neuropathies. IMP dehydrogenases IMPDH IMPDH family Inosine 5'-monophosphate dehydrogenases Inosine monophosphate dehydrogenase family IMPDH Guanosine monophosphate reductase catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. The two human genes encoding guanosine monophosphate reductase share 79% amino acid sequence identity. GMP reductases GMPR GMPR family Guanosine monophosphate reductase family GMPR IMP dehydrogenase (IMPDH) and GMP reductase (GMPR) belong to the same family of (beta/alpha)8 TIM-barrel enzymes. They bind the same ligands with similar affinities and share a common set of catalytic residues. Both enzymes catalyze a hydride transfer reaction involving a nicotinamide cofactor hydride, and both reactions proceed via the same covalent intermediate. In the case of IMPDH, this intermediate reacts with water while in GMPR it reacts with ammonia. In both cases, the two chemical transformations are separated by a conformational change. In IMPDH, the conformational change involves a mobile protein flap while in GMPR the cofactor moves. IMPDH/GMPR family Dihydrofolate reductase (DHFR) activity is an important enzymatic function that resides within the one carbon metabolism (OCM) pathway. Its central role in cellular metabolism in support of cell division and proliferation has made DHFR an attractive and successful drug target. Methotrexate is a direct inhibitor of DHFR. There are two human genes capable of encoding dihydrofolate reductase: intron-containing DHFR and a retrogene, DHFR2, which shares 92% amino acid sequence identity with DHFR. Although DHFR2 is transcribed, targeted proteomics analysis found only a low abundance of translated protein in human embryonic heart and no evidence of DHFR2 protein in adult cells. DHFR2 functionality may lie at the RNA level. DHFR DHFR family Dihydrofolate reductases Dihydrofolate reductase family DHFR The members of the family of aromatic amino acid hydroxylases, phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase, are defined both by their amino acid substrates and by the use of a tetrahydropterin to provide the electrons for the monooxygenation reaction these enzymes catalyze. Amino acid hydroxylases Amino acid monooxygenases Pterin-dependent aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase and tryptophan hydroxylase family Aromatic amino acid hydroxylase family Vitamin K epoxide reductase is a crucial enzyme in blood coagulation and the target of the most commonly used oral anticoagulant warfarin. There are two isoforms of this enzyme encoded by VKORC1 and VKORC1L1. The proteins share ~50% amino acid sequence identity and catalyze both vitamin K epoxide reductase and vitamin K quinone reductase enzymatic activities. VKOR family VKORC Vitamin K 2,3-epoxide reductases Vitamin K quinone reductases Vitamin k epoxide reductases Vitamin K epoxide reductase complex subunit 1 family VKORC Type II receptor serine/threonine kinases Type 2 receptor serine/threonine kinases LAR transmembrane tyrosine phosphatase-interacting proteins PPFI leukocyte common antigen-related protein tyrosine phosphatase (LAR-RPTPs)-interacting protein family PPFI scaffold protein family PPFI 7BS non-methyltransferases NALCN regulates the resting membrane potential by mediating the Na+ leak current in neurons, and it functions as a channelosome in complex with NALF1, UNC79, and UNC80. Dysfunction of the NALCN channelosome causes a broad range of neurological and developmental diseases called NALCN channelopathies in humans. NALCN channelosome NALCN-FAM155A-UNC79-UNC80 channel complex NALCN channel complex subunits Evolutionary analysis indicates that ARC is derived from a vertebrate lineage of Ty3/gypsy retrotransposons, which are also ancestors to retroviruses. These findings suggest that Gag retroelements have been repurposed during evolution to mediate intercellular communication in the nervous system. Retrotransposon Gag derived ARC ASPRV1 is one of the human genes that have been domesticated from retrotransposons during vertebrate evolution. The protein expressed from this gene was defined as a retrovirus Gag-like protein as — besides its enzymatic domain — it contains a domain that is homologous to that of the Gag structural domain of the canonical retroviral polyprotein. The evolutionary origin was demonstrated by the homology between its Gag-like and protease domains and those of the retrovirus/retrotransposon proteins. Retrotransposon derived ASPRV1 Helix-turn-helix motif of pipsqueak (HTH-Psq) proteins are a family of transcription factors derived from a pogo-type transposase, known as the pipsqueak transposase. HTH-Psq family Helix-turn-helix motif Psq family Mammalian genomes comprise many active and fossilized retroelements. The obligate requirement for retroelement integration affords host genomes an opportunity to 'domesticate' retroelement genes for their own purpose, leading to important innovations in genome defense and placentation. While many such exaptations involve retroviruses, the L1TD1 gene is the only known domesticated gene whose protein-coding sequence is almost entirely derived from a LINE-1 (L1) retroelement. LINE1 element derived gene FLYWCH is a distinct DNA-binding family known to have originated from the Mutator transposase. FLYWCH family The importance of ribonucleotide reductase (RNR) lies in its unique ability to catalyze the rate-limiting step of the reduction of ribonucleotides (NDPs) to the corresponding deoxyribonucleotides (dNDPs), the precursors of DNA. Mammalian RNRs consist of two homodimeric subunits, which associate to form the holoenzyme. The large RRM1 dimer contains the catalytic site, whereas the smaller dimer (RRM2 or RRM2B) contains an oxygen-requiring di-iron tyrosyl-radical site, which is essential for catalysis. RNRs RRM Ribonucleoside-diphosphate reductases Ribonucleotide reductase subunits RRM Most mammalian genomes contain decayed piggyBac transposons. They ceased their activity due to several mutations or rearrangements. The human genome contains at least five domesticated piggyBac genes, designated from PGBD1 to PGBD5. On the one hand, PGBD1 and PGBD2 were probably present in the common ancestor of mammals, while PGBD3 and PGBD4 are restricted to primates. On the other hand, PGBD5, the only sequences interrupted by multiple introns, are not only orthologous in mammals and fish but also in lamprey and lancelet suggesting an ancient domestication event about 525 Ma before cephalocordates and vertebrates split from urochordates. PGBD PiggyBac transposable element derived family PGBD The human genome encodes two proteins with homology to proteins encoded by Harbinger elements: HARBI1, a domesticated transposase-derived protein, and NAIF1, which contains a trihelix motif similar to that described in the Harbinger Myb-like protein. Physical interaction, subcellular localization, and DNA-binding activities of HARBI1 and NAIF1 suggest strong functional homologies between the Harbinger3_DR system and their related, host-encoded counterparts. Harbinger transposase derived genes Genes in this family contain a tranposase domain derived from domestication of a mariner transposable element. Mariner transposase derived genes The RAG1 and RAG2 genes have been derived from a RAG transposon related to Transib DNA transposons approx. 500–600 million years ago . RAG transposon derived genes Synucleins are small, highly conserved proteins that are intrinsically disordered or unstructured and prone to aggregation. Synucleins are abundant proteins that are mainly found in neural tissue. Although synucleins have been well-studied in the context of neurodegeneration and cancer, a clear biological function for synuclein proteins remains poorly understood. SNC Synucleins Synuclein family SNC Glutathione peroxidases are enzymes that catalyse the reduction of H2O2 or organic hydroperoxides to water or the corresponding alcohols, typically in a glutathione-dependent manner. Five family members (GPX1-4, GPX6) are selenoproteins with a selenocysteine residue at the active site while the other three (GPX5, 7-8) have a cysteine residue at the active site. GPX Glutathione peroxidase family GPX Heme-containing peroxidases have a highly conserved structure and evolved to catalyze the oxidation of various substrates in the presence of H2O2 to serve diverse functions. MPO, EPX, and LPO have antimicrobial activities and serve in the first line of host defense, whereas TPO has an essential role in the biosynthesis of thyroid hormones. PDXN is involved in protein cross-linking in the extracellular matrix (ECM). PXDNL shares a high level of identity with PXDN but has lost its enzymatic activity. Heme peroxidases The ZIC family comprises five members (ZIC1-5), homologous with the odd-paired (OPA) gene in Drosophila melanogaster. These transcription factors contain five Cys2His zinc finger domains, constituting one of the most abundant transcription factor families in human cells. ZIC proteins significantly contribute to transcriptional regulation and chromatin remodeling. ZIC ZIC family ZIC transcription factors zinc finger protein of the cerebellum family ZIC family zinc fingers ZIC Immunoglobulins (IG) or antibodies are antigen receptors of the B cells of the adaptive immune response, acquired by jawed vertebrates (or gnathostomata) more than 450 million years ago and found in all extant jawed vertebrate species from fishes to humans. IG are anchored in the membrane of a B cell as part of a signaling B cell receptor (BcR = membrane IG+CD79) or are secreted by plasmocytes. IG recognize antigens in their native (unprocessed) form. IG are made of two identical heavy (H) chains and two identical light (kappa or lambda) chains, encoded by genes located in three major loci: the IG heavy (IGH) locus at 14q32.33, IG kappa (IGK) locus at 2p11.2 and IG lambda (IGL) locus at 22q11.2. Genes outside of these major loci are orphons. There are four IG gene types, variable (V), diversity (D) (only for IGH), joining (J) and constant (C) genes which contribute to the IG chain synthesis. The variable domain at the N-terminal end of each IG chain results from a V-(D)-J rearrangement whereas the remaining of the chain, or constant region, is encoded by a C gene. The combinatorial and junctional diversity together with IG somatic hypermutations create a huge diversity of 1012 specific IG per individual, the limiting factor being only the number of B cells that an organism is genetically programmed to prod IG Immunoglobulins IG The Krueppel-associated box (KRAB) is a domain of around 75 amino acids that is found in the N-terminal part of about one third of eukaryotic Krueppel-type C2H2 zinc finger proteins (ZFPs). It is enriched in charged amino acids and can be divided into subregions A and B, which are predicted to fold into two amphipathic α-helices. The KRAB A and B boxes can be separated by variable spacer segments and many KRAB proteins contain only the A box Krueppel-associated box containing KRAB domain containing Fibrinogen is a hexameric coagulation factor containing 2 polypeptide chains encoded by each of the 3 fibrinogen genes (FGA, FGB, and FGG). These genes are clustered within a 65-kilobase region on human chromosome 4. During coagulation, fibrinogen is converted to fibrin via thrombin-mediated proteolytic cleavage. FG Fibrinogen coagulation factor I Fibrinogen chains FG The CILK1, MAK and MOK protein kinases are subfamily of CMGC kinases that share very similar N-terminal catalytic domains but differ markedly in the structural organization and features in their C-terminal non-catalytic domains. ICK/MAK/MOK protein kinases RCK family CILK1, MAK, MOK protein kinase family SRSF protein kinases (SPRKs) constitute a subfamily of CMGC serine-threonine kinases that specifically phosphorylate serine residues within regions that are rich in serine-arginine dipeptide motifs, also called SR domains. The serine-arginine splicing factors (SRSFs) are the primary substrates for the SRPKs. SRPK Serine-arginine protein kinases serine/arginine-rich splicing factor kinases SRSF protein kinase family SRPK Ubiquitin is produced by four distinct genes: two of these, UBA52 and RPS27A, encode a single copy fused to ribosomal subunits, whereas the other two, UBB and UBC, are polyubiquitin genes encoding three and nine head-to-tail repeats of ubiquitin, respectively. Free ubiquitin is cleaved from these gene products by peptidases that belong to the deubiquitylating family of enzymes (DUBs). Ubiquitylation principally occurs at lysine residues of substrate proteins, creating an isopeptide bond. Ubiquitination was initially recognised as a signal for proteasome-mediated degradation but is now known to be fundamental to the control of many cellular processes. UB Ubiquitins UB The serum and glucocorticoid kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK1, SGK2 and SGK3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. SGKs have been implicated in the regulation of cell growth, proliferation, survival and migration: cellular processes that are dysregulated in cancer. SGK SGK family SGK kinases Serum/glucocorticoid regulated kinase family SGK The MAST kinases are highly conserved across nearly all eukaryotic groups, from single-celled protists to complex plants and animals. MAST1-4 are atypical in the AGC family. These large kinases possess multiple functional domains outside the AGC kinase core including the N-terminal domain of unknown function (DUF1908) and C-terminal PDZ domain. MASTL is shorter than the others as it only contains the kinase domain. MAST MAST kinases Microtubule associated serine/threonine kinase family MAST The G protein–coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein–coupled receptors (GPCRs) as their primary substrates. GRK GRK family G protein-coupled receptor kinase family GRK The STK38/LATS family of kinases is a subclass of the AGC group of serine/threonine protein kinases. Members of the STK38/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. Notably, all STK38/LATS kinases share two unique characteristics, a conserved N-terminal regulatory domain (NTR) in proximity to the catalytic domain and an insertion between subdomains VII and VIII of the catalytic domain. NDR/LATS kinase family NDR/LATS protein kinases nuclear Dbf2-related/large tumour suppressor family of kinases STK38/LATS kinase family The DMPK kinases are members of the AGC kinase family with a conserved domain architecture of N-terminal kinase domains followed by a predicted coiled-coil domain and C-terminal regulatory domains that mediate a variety of protein-protein and protein-membrane interactions. While many AGC kinases are regulated by phosphorylation of motifs in their activation loop or C-terminal tail,26 the DMPK kinases are not. Instead, their N-terminal capped-helix bundle (CHB) domain cooperates with the C-terminal tail to maintain the kinase domain in a homodimeric, active conformation with an ordered activation loop. Protein kinases of the DMPK family are critical regulators of actomyosin contractility in cells. DMPK family dystonia myotonica protein kinase family DMPK kinase family The IGH locus is at 14q32.33 and contains IGHV (variable) genes, IGHD (diversity) genes, IGHJ (joining) genes, and IGHA, IGHG, IGHD, IGHE and IGHM constant genes. IGH Immunoglobulin heavy locus at 14q32.33 IGH The CDC42 binding protein kinase family are serine/threonine kinases within AGC kinases that share a kinase domain closely related to DMPK. CDC42BP kinases are downstream effectors of CDC42 that play key roles in actin-myosin regulation and activities including cell adhesion, motility and invasion. CDC42 binding kinases CDC42BP MRCKs Myotonic dystrophy kinase-related Cdc42-binding kinases CDC42 binding protein kinase family CDC42BP Rho associated coiled-coil kinases (ROCKs) are effectors of Rho family of small GTPases. ROCKs have multiple functions that include regulation of cellular contraction and polarity, adhesion, motility, proliferation, apoptosis, differentiation, maturation and remodeling of the extracellular matrix (ECM). ROCKs have an N-terminal kinase domain, a coiled-coiled region, Rho-binding domain, a pleckstrin homology domain and a cysteine-rich domain at the C-terminal. ROCK ROCKs RhoA binding coiled-coil containing kinases Rho associated coiled-coil containing protein kinase family ROCK LATS1 and LATS2 are serine/threonine kinases of the AGC subfamily, most closely related to the serine/threonine kinase 38 family (also known as nuclear Dbf2-related kinases or NDRs). The LATS family have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP1/WWTR1 (YAP/TAZ), the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53. LATS LATS kinases Large tumor suppressor kinase family LATS STK38 and STK38L (also know as NDR1 and NDR2) are highly related AGC family serine/threonine kinases that are evolutionarily conserved from yeast to mammals. In various organisms they have been implicated in cellular proliferation, transcriptional asymmetry, DNA damage response, innate immunity, ciliogenesis, mitochondrial health and neuronal development. NDR kinases STK38 nuclear Dbf2-related kinases Serine/threonine kinase 38 family STK38 The protein kinase N (PKN) family of serine/threonine protein kinases belongs to the AGC subfamily of protein kinases and is closely related to the protein kinase C (PKC) family. The PKN catalytic domains share approximately 50% sequence identity with the PKC family members. However, the N-terminal regulatory regions are radically different between the PKN and PKC kinases. All PKN family members exhibit three unique polybasic coiled-coil homology region 1 (HR1)-domains (also called antiparallel coiled-coil (ACC)-domains), which confer binding and regulation by the Rho family of small GTPases as well as a lipid regulated autoinhibitory C2-like domain. PKN PKNs Protein kinase Ns Protein kinase N family PKN L-lactate dehydrogenase (LDH, EC1.1.1.27) is a key enzyme that catalyzes the interconversion of L-lactate and pyruvate with nicotinamide adenine dinucleotide (NAD+) as a coenzyme. This enzyme exists in a tetrameric form by combination of M (muscle, LDHA) and H (heart, LDHB) subunits in various proportions in different somatic tissues. There are five major tetrameric LDH complexes consisting of LDHA and/or LDHB subunits. Expression of LDHC, LDHAL6A and the intronless gene LDHAL6B is restricted to testes where they may play a role in spermatogenesis. L-lactate dehydrogenase family Sphingosine kinases catalyzes the formation of sphingosine-1 phosphate (S1P). S1P plays an important role in regulation of a variety of biological processes through intracellular and extracellular actions. SPHK Sphingosine kinase family SPHK HOOK domain containing These are IGH genes that are found outside of the 14q32.33 IGH locus and therefore cannot form part of an immunoglobulin-encoding gene. Immunoglobulin heavy (IGH) orphons There are three Hook proteins expressed in mammalian cells, characterized by three conserved regions: a globular N-terminal Hook domain, a central coiled-coil domain that drives dimerization and forms a 31-nm helix that aligns along the Arp1 filament, and a divergent, predicted unstructured C-terminal domain thought to mediate cargo binding. HOOK family Hook-related proteins (HkRP) like Girdin (CCDC88A), DAPLE (CCDC88C), and Gipie (CCDC88B) are actin-binding proteins, implicated in actin organization and in cell motility. HkRP family HOOK related protein family The endocannabinoid system (ECS) defines two types of endogenous agonist: esters and amides of fatty acids. The esters and amides are synthesised by two independent enzyme systems; separate hydrolases also terminate their action. The functions of these endocannabinoids are primarily mediated through two G protein-coupled receptors (encoded by CNR1 and CNR2). Endocannabinoid hydrolases The endocannabinoid 2-arachidonoylglycerol (2-AG) is a lipid mediator involved in various physiological processes. In response to neural activity, 2-AG is synthesized post-synaptically, then activates pre-synaptic type 1 cannabinoid recep tors, resulting in transient and long-lasting reduction of neurotransmitter release. The signalling competence of 2-AG is tightly regulated by the balanced action between 'on demand' biosynthesis and degradation. The major enzymatic route for 2-AG inactivation in brain is via hydrolysis; three serine hydrolases (MGLL, BHD6 AND ABHD12) account for approx. 99% of brain 2-AG hydrolase activity. 2AG hydrolases 2-arachidonoylglycerol hydrolases N-arachidonoylethanolamine (AEA), also known as anandamide, is an endogenous cannabinoid that is a partial agonist of both cannabinoid receptors (CNR1 and CNR2). Termination of AEA signalling is mediated by hydrolytic enzymes. Fatty acid amide hydrolase (FAAH) appears to be a primary regulator of AEA (and other N-acylethanolamine) levels inside the cell. N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme, particularly associated with macrophages, which is also able to hydrolyse N-acylethanolamines, including AEA. FAAH2, in contrast to FAAH and NAAA, is not found in murids, but is found in human, and is also able to hydrolyse AEA and other N-acylamides, with a physical association with intracellular lipid droplets. The differential tissue and subcellular locations of these enzymes is presumed to regulate AEA (and other N-acylamides) in a differential manner. AEA hydrolases Anandamide amidohydrolases anandamide hydrolases N-arachidonoylethanolamine hydrolases AOX1 and XDH are classified as molybdo-flavoenzymes, since they require FAD besides Moco to oxidize their substrates. The primary structure of AOX1 and XDH is very similar and the catalytically active form of both types of enzymes is a homodimer consisting of two 150 kDa subunits. The monomeric subunit of both AOX1 and XDH is divided into three distinct regions: an amino-terminal 25-kDa domain containing two non-identical 2Fe/2S redox centers, a central 40-kDa domain where the FAD-binding site is located and a carboxy-terminal 85-kDa domain consisting of the Moco-binding site mapping close to the substrate pocket. XDH and AOX1 differ in their substrate specificity. XDH acts preferentially on the two purines, hypoxanthine and xanthine, oxidizing them to xanthine and uric acid, respectively. XDH is a key enzyme in the catabolism of purines. In contrast, the physiological role of human AOX1 is still a matter of debate but the substrate specificity is much broader and AOX1 is known to play an important role in the metabolism of drugs and other xenobiotics. AOX/XDH family Aldehyde oxidase family Xanthine dehydrogenase family molybdo-flavoenzymes xanthine oxidase family of Moco-containing enzymes Xanthine dehydrogenase/aldehyde oxidase family The three protein-coding members of the tyrosinase family play a crucial role in determining melanin production and coloration of animal pigment cells. These proteins are anchored to the melanosomal membrane through a C-terminal fragment. They share approximately 40% amino acid identity and the same structural features, including a signal peptide, a Cys-rich domain, two metal binding sites and a transmembrane domain. Tyrosinase (TYR) catalyzes the first two steps of the Raper–Mason pathway, the hydroxylation of l-tyrosine to l-DOPA and the subsequent oxidation of l-DOPA to l-dopaquinone. The first activity is called tyrosine hydroxylase, and the second one o-diphenol oxidase, catechol oxidase or DOPA oxidase. Dopachrome tautomerase (DCT, previously TYRP2) catalyzes the conversion of dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA). TYRP1 is abundant in melanocytes and mutations can result in oculocutaneous albinism type 3 (OCA3) but the precise role of TYRP1 in human melanogenesis remains unclear. TYR Tyrosinase family TYR The mitochondrial calcium uniporter channel exists as a channel composed of a total of 4 MCU subunits and up to 4 SMDT1 subunits. In some cases, the dominant-negative MCU paralog, MCUB, replaces MCU subunits within the complex. The channel is gated by dimers of MICU1/2 or, in some tissues, dimers of MICU1/3. The accessory subunit MCUR1 also binds to and regulates the channel. Two uniporter channels can dimerize, and the function of these dimers is regulated by interactions between the MICU2 subunit associated with each channel. MCUC mitochondrial calcium uniporter channel mitochondrial calcium uniporter complex MCU complex subunits STK32A, STK32B and STK32C are closely related serine/threonine kinases that form a subfamily within the AGC family kinases. STK32 YANK family Yet another kinase family Serine/threonine kinase 32 family STK32 Protein kinase A (PKA) is composed of two regulatory (R) subunits forming a dimer, and two catalytic (C) subunits bound to the R subunits. Five different established or putative C subunit encoding genes have been identified in the human genome; PRKACA, PRKACB, PRKX, PRKY, and PRKACG. The PKA C subunit encoded by PRKACA was the first PK for which the 3D structure was solved and it has been extensively studied. Several structure-function-relationships encoded by PRKACA have proved to be conserved features of protein kinases (PKs) in general. The conserved catalytic core consists of an N-terminal lobe, called the small lobe or N-lobe, comprising mainly β-strands and a single α-helix. Located C-terminally is the large lobe or C-lobe, consisting mostly of α-helices. Between the small and large lobes is the active site cleft which binds an ATP molecule and two divalent cations. These cations are essential in the process of transferring the γ-phosphate of ATP to Ser or Thr residues on PKA substrates. The N- and C-terminal parts of PKs outside of the conserved catalytic core are termed the N- and C-tail, respectively. In the AGC subfamily of PKs, which includes PKA, the C-tail shares conserved features important for AGC kinase functioning, including a docking site for the AGC kinase activator PDK1. In contrast, the N-tail is highly variable even among the different PKA C subunits. PRKAC cyclic AMP-dependent protein kinase catalytic subunits protein kinase cAMP-activated catalytic subunit family Protein kinase A family PRKAC The human IGK locus is at 2p11.2 and contains IGKV (variable) genes, IGKJ (joining) genes and one IGKC (constant) gene. Most individuals have two clusters of the IGKV genes resulting from a duplication. The clusters are designated as either proximal or distal to the IGKC gene. Genes from the distal cluster are denoted with a 'D' in the symbol while those without a 'D' are located in the proximal cluster. IGK Immunoglobulin kappa locus at 2p11.2 IGK The protein kinase G family comprises two closely related genes (PRKG1 and PRKG2) that encode cGMP-dependent serine/threonine kinases (often referred to as cGKs). These enzymes have a rod-like structure and are activated at submicromolar to micromolar concentrations of cGMP. They are composed of three functional domains: an N-terminal (A) domain, a regulatory (R) domain, and a catalytic (C) domain. The regulatory domain contains two tandem cGMP-binding sites that interact allosterically and bind cGMP with high and low affinity. Occupation of both binding sites induces a large change in secondary structure to yield a more elongated molecule. The catalytic domain contains the MgATP- and peptide-binding pockets. Binding of cGMP to both sites in the R domain releases the inhibition of the catalytic center by the N-terminal autoinhibitory/pseudosubstrate site and allows the phosphorylation of serine/threonine residues in target proteins and in the N-terminal autophosphorylation site. In addition to controlling activation and inhibition of the catalytic center, the N terminus has two other functions: dimerization, cGKs are homodimers that are held together by a leucine zipper present in the N terminus, and targeting, the enzymes are targeted to different subcellular localizations by their N termini. PRKG cGKs cyclic GMP-dependent protein kinases Protein kinase G family PRKG Mediates epigenetic repression, responsible for position-effect variegation of integrated transgenes in human cells. Recruited to genomic loci rich in H3K9me3, where subsequent recruitment of the histone methyltransferase SETDB1 (Q15047) is required for further H3K9me3 deposition to maintain transcriptional silencing. Acts with MORC2 (Q9Y6X9) to repress LINE-1 class I transposable elements. HUSH epigenetic repressor complex human silencing hub complex HUSH complex Putative lysine methyltransferases The complement membrane attack complex (MAC) is classically known as a cytolytic effector of innate and adaptive immunity that forms pores in the plasma membrane of pathogens or targeted cells, leading to osmolysis. C5b-9 Complement Membrane Attack complex MAC Membrane Attack complex MAC The SAND domain is a conserved sequence motif found in a number of nuclear proteins, including the Sp100 family and NUDR (HGNC note - 'NUDR' is an alias and this gene has the approved symbol <a href='https://genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14677'>DEAF1</a>). These are thought to play important roles in chromatin-dependent transcriptional regulation and are linked to many diseases. We have determined the three-dimensional (3D) structure of the SAND domain from Sp100b. The structure represents a novel alpha/beta fold, in which a conserved KDWK sequence motif is found within an alpha-helical, positively charged surface patch. SAND domain containing Glutamate-oxalacetate transaminase (GOT) is a pyridoxal phosphate-dependent enzyme that exists in cytoplasmic and mitochondrial forms, GOT1 and GOT2, respectively. The two enzymes belong to the class-I pyridoxal-phosphate-dependent aminotransferase family, and are homodimeric, showing close homology. GOT1 is an important regulator of glutamate levels, as it is involved in the biosynthesis of L-glutamate from L-aspartate or L-cysteine. In addition, the aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. GOT2 catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid and the reversible transamination of L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate. GOT2 plays a key role in amino acid metabolism and the metabolite exchange between mitochondria and cytosol. It also facilitates cellular uptake of long-chain free fatty acids. Aspartate aminotransferase family Aspartate transaminases GOT Glutamic-oxaloacetic transaminase family GOT Transaminases (or Aminotransferases) (Enzyme Commission [EC] 2.6.1.-) are pyridoxal 5′-phosphate–dependent enzymes that catalyze the transamination reactions between amino acid donor and keto acid acceptor substrates. Aminotransferases Transaminases Branched chain aminotransferases (BCATs) (EC 2.6.2.42) catalyze transamination of the branched chain amino acids (BCATs) leucine, isoleucine, and valine. Structurally, the BCATs belong to the fold type IV class of pyridoxal phosphate (PLP) enzymes. Vertebrate BCATs are homodimers. In eukaryotes there are two isozymes, one is cytosolic (BCAT1) and the other is mitochondrial (BCAT2). In mammals, BCAT1 is largely restricted to the central nervous system and BCAT2 is in most tissues. BCAT branched chain amino acid transaminases Branched chain amino acid transaminase family BCAT The key enzyme in the de novo production of UDP-GlcNAc through the hexosamine biosynthesis pathway is glutamine--fructose-6-phosphate amidotransferase (GFPT). GFPT is present in all cellular organisms, including prokaryotes and eukaryotes, underscoring the importance of this enzyme and the HBP for normal cell function. The two mammalian paralogs, GFPT1 and GFPT2, share 75–80% amino acid sequence identity. GFPT1 is found more ubiquitously, whereas GFPT2 seems to have higher expression in tissues of the central nervous system. GFPT comprises an N-terminal 27 kDa glutaminase domain that catalyzes the hydrolysis of glutamine to glutamate and ammonia. The C-terminus harbors the 40 kDa isomerase domains that use ammonia to convert fructose-6-P (a glycolytic intermediate) to glucosamine-6-phosphate (GlcN-6-P). This reaction is the rate-limiting step of the de novo synthesis of hexosamines. GFPT Glutamine--fructose-6-phosphate transaminase family GFPT These are IGK genes that are found outside of the 2p11.2 IGK locus and therefore cannot form part of an immunoglobulin-encoding gene. Immunoglobulin kappa (IGK) orphons Glutamic--pyruvic transaminase (also known as alanine aminotransferase) catalyzes the reversible transamination between alanine and 2-oxoglutarate to generate pyruvate and glutamate, playing a key role in the intermediary metabolism of glucose and amino acids. There are two isoforms in human encoded by GPT and GPT2 that show differential expression and subcellular localisation. Alanine aminotransferases Alanine transaminases GPT Glutamic--pyruvic transaminase family GPT Dual-specificity tyrosine-regulated kinases (DYRKs) comprise a family of protein kinases within the CMGC group of the eukaryotic kinome. DYRK proteins are defined as dual-specificity protein kinases because they have phosphorylation activity on tyrosine, serine, and threonine residues, although the tyrosine phosphorylation activity is restricted to auto-phosphorylation. DYRK DYRK family Dual-specificity tyrosine-regulated kinase family DYRK PRP4K is the sole member of a CMGC kinase subfamily. PRP4 family PRP4K PRP4K family Pre-mRNA processing factor kinase PRP4K family The protein kinase C family of serine/threonine protein kinases belong to the AGC subfamily of protein kinases. PRKCs (often called PKCs) can be subdivided into three groups based on structure: the group of the conventional PRKC enzymes containing PRKCA, PRKCB and PRKCG isoforms; novel PRKCs consisting of PRKCD, PRKCE, PRKCH and PRKCQ; and the group of atypical PRKCs consisting of PRKCZ and PRKCI isoforms. PKCs PRKC Protein kinase C family PRKC RPS6K Ribosomal protein S6 kinase family RPS6K PDPK1 is the sole member of this AGC kinase subfamily. PDK1 family PDPK1 Protein kinase B family 3-phosphoinositide dependent protein kinase 1 family PDPK1 Lysine methyltransferases The IGL locus is at 22q11.2 and contains IGLV (variable) genes, IGLJ (joining) genes and IGLC (constant) genes. IGL Immunoglobulin lambda locus at 22q11.2 IGL ELOVL ELOVLs very-long-chain fatty acid elongases ELOVL fatty acid elongase family ELOVL Epsins are a family of endocytic adaptor proteins composed of 3 paralogs: EPN1, EPN2 and EPN3. Epsins are known to be involved in the first steps of endocytosis in particular there is evidence that they have a specific role in cargo selection and coat assembly. From a structural perspective, epsins share a similar protein structure. They possess an epsin N-terminal homology (ENTH) domain necessary to bind PtdIns(4,5)P2 at the PM, two or three ubiquitin interacting motifs (UIMs) known to bind to ubiquitinated cargoes, and the aspartate-proline-tryptophan (DPW) and asparagine-proline-phenylalanine (NPF) motifs that interact with the clathrin machinery. Since the protein structure of the three isoforms is similar, redundant functions have been observed in endocytosis, regulation of the actin cytoskeleton during clathrin-mediated endocytosis, and development. Epsin Epsin endocytic adaptor proteins Epsin family The ethanolamine kinases, and closely related choline kinases, catalyze the first step of the Kennedy pathway, which is the ATP-dependent phosphorylation of ethanolamine or choline, forming PE or PC, respectively, and the byproduct ADP. Mammalian cells carry two ethanolamine-specific kinases: ETNK1 and ETNK2 that have negligible choline kinase activity. ETNK Ethanolamine kinase family ETNK Choline kinases catalyse the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction. Functional choline kinase exists as a dimer, and can form homodimers or heterodimers with differential dynamics dependent on the tissue type. CHKA homodimers display higher enzymatic activity than CHKB homodimers and CHKA/B heterodimers with tissues differing in their relative expression of the varying isoforms. CHK Choline kinase family CHK NOX NOX/DUOX family NADH oxidase family NOX DUOX Dual oxidase family DUOX SESN Sestrin family SESN The dual oxidase maturation factor genes (DUOXA1 and DUOXA2) are arranged head-to-head to and co-expressed with their respective dual oxidase genes (DUOX1 and DUOX2). The genomic rearrangement leading to linkage of ancient DUOX and DUOXA genes can be traced back before the divergence of echinoderms. Dual oxidase maturation factors allow ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional DUOXs. DUOXA Dual oxidase auxiliary subunits Dual oxidase maturation factors Dual oxidase maturation factor family DUOXA CAMK2 calcium/calmodulin dependent protein kinase II family CAMK2 family CAMK2 These are IGL genes that are found outside of the 22q11.2 IGL locus and therefore cannot form part of an immunoglobulin-encoding gene. Immunoglobulin lambda (IGL) orphons PHKG Phosphorylase kinase catalytic subunits Phosphorylase kinase catalytic subunit gamma family PHKG CAMK1 calcium/calmodulin dependent protein kinase I family CAMK1 family CAMK1 CASK is a unique MAGUK protein that contains an N-terminal CaM-kinase domain besides the typical MAGUK domains. The CASK CaM-kinase domain was presumed to be a catalytically inactive pseudokinase because it lacks the canonical DFG motif required for Mg2+ binding that was thought to be indispensable for kinase activity. However, it has been shown that CASK functions as an active protein kinase even without Mg2+ binding. High-resolution crystal structures revealed that the CASK CaM-kinase domain adopts a constitutively active conformation that binds ATP and catalyzes phosphotransfer without Mg2+. The CASK CaM-kinase domain phosphorylates itself and at least one physiological interactor, the synaptic protein neurexin1 (NRXN1), to which CASK is recruited via its PDZ domain. CASK CASK family CASK CHEK2 Chk2 family RAD53 family Checkpoint kinase 2 family CHEK2 HUNK hormonally up-regulated Neu-associated kinase family HUNK family kinases HUNK SNF related kinase family SNRK SNRK family kinases SNRK LKB subfamily Liver kinase B1 family STK11 STK11 family kinases STK11 NIM1 serine/threonine protein kinase family NIM1K NIM1K family kinases NIM1K PAS domain containing serine/threonine kinases PASK PASK family kinases PASK STK33 serine/threonine kinase 33 family STK33 family kinases STK33 CAMKV CaM kinase like vesicle associated family CAMKV family CAMKV MKNK MAPK interacting serine/threonine kinase family MKNK MAPKAPK MAPKAPK family MAPKAPK TRIO/KALRN family TRIO family TRIO/KALRN family Insulin receptors and the related receptor family members, IGF1 receptors and insulin receptor-related receptors are expressed at the cell surface as preformed heterotetramers, each comprising two hemi-receptors composed of one α- and one β-subunit. Each α- and β-subunit and the two α-subunits are cross-linked by disulphide bridges. The extracellular α subunits bind insulin or IGFs. The β-subunits have a tyrosine kinase domain. INSR and IGF1R have high sequence homology in the cytoplasmic tyrosine kinase domain, with greater divergence in the extracellular ligand-binding α-subunits. INSRRs have high homology with INSRs and IGF1Rs in the tyrosine kinase domain, but the extracellular α-subunit is divergent and does not bind insulin or IGFs. INSRRs operate as alkali sensors: exposure to extracellular alkaline pHo (pHo>8.0) causes a conformational change in the α subunit that activates the intracellular tyrosine kinase resulting in Tyr-phosphorylation of the β-subunit with activation of downstream signalling. INSR Insulin receptor family Phosphofructokinase (PFK) catalyses the phosphorylation of fructose 6-phosphate (F6P) to fructose 1,6-bisphosphate (F1,6BP) and plays a central role in the glycolytic pathway. The human enzymes are encoded by 3 paralogous genes: PFKM, PFKL and PFKP. While the isoforms were named for the tissue that they are prevalent or originally found (muscle, liver and platelet respecitively) they are not limited to these tissues. The functional enzyme is a tetramer and can be formed from one or more isoforms. The kinetic/regulatory properties vary with subunit composition. 6-phosphofructo-1-kinase subunits PFK Phosphofructokinase family PFK Lactate exists in the human body as two optical isomers: L-lactate and D-lactate. L-lactate is produced from pyruvate during anaerobic glycolysis and present in blood at concentrations 100 times greater than D-lactate. D-lactate is acquired exogenously by consumption of foods, by metabolism of chemicals such as propylene glycol, by intestinal bacteria production, or endogenously by methylglyoxal metabolism—a toxic product that is converted to D-lactate. Different classes of lactate dehydrogenase act on the different isomers. LDHD is specific for D-lactate metabolism. D-lactate dehydrogenase family Lactate exists in the human body as two optical isomers: L-lactate and D-lactate. The term lactate dehydrogenase usually refers to the enzymes that are involved in the metabolism of L-lactate however there is also a single, unrelated, enzyme that can act on D-lactate. LDH Lactate dehydrogenases LDH Adenylate kinases are abundant phosphotransferases that catalyze the interconversion of adenine nucleotides and thus regulate the adenine nucleotide ratios in different intracellular compartments. AK Adenylic kinases Adenylokinases Adenylate kinases AK Malate dehydrogenase (MDH) catalyzes the oxidation of L-malate to oxaloacetate in a reversible, NADH-dependent manner. MDH1 encodes a cytosolic protein that functions in multiple pathways, including the malate-aspartate shuttle and gluconeogenesis. MDH2 encodes a mitochondrial protein that catalyzes an essential step in the citric acid cycle. The main isoforms of MDH1 and MDH2 have been well characterized biochemically; both function as dimers. Domains for substrate binding, nucleotide binding, and dimer formation are highly conserved. MDH1B is predicted to have malate dehydrogenase activity but has not been tested to date. MDH1 and MDH2 are widely expressed, while MDH1B is only expressed in a small subset of tissues. MDH Malate dehydrogenases MDH Myosin holoenzyme components Myosin molecule components Myosin chains ADP Ribosylation Factors (ARFs) are members of the ARF family of GTP-binding proteins of the Ras superfamily. ARF family proteins are ubiquitous in eukaryotic cells, and six highly conserved members of the family have been identified in mammalian cells. Although ARFs are soluble, they generally associate with membranes because of N-terminus myristoylation. They function as regulators of vesicular traffic and actin remodelling. The small ADP ribosylation factor (Arf) GTP-binding proteins are major regulators of vesicle biogenesis in intracellular traffic. They are the founding members of a growing family that includes Arl (Arf-like), Arp [ARFRP] (Arf-related proteins) and the remotely related Sar (Secretion-associated and Ras-related) proteins. ADP ribosylation factor GTPase family ARF GTPase family The Ras superfamily is a protein superfamily of small GTPases, which are all related, to a degree, to the Ras protein subfamily (the key human members of which are KRAS, NRAS, and HRAS ). There are more than a hundred proteins in the Ras superfamily. Ras small GTPase superfamily The Wnt protein family includes a large number of cysteine-rich glycoproteins. The Wnt proteins activate signal transduction cascades via three different pathways, the canonical Wnt pathway, the noncanonical planar cell polarity (PCP) pathway, and the noncanonical Wnt/Ca2+ pathway. WNT WNT signaling gene family Wingless-type MMTV integration site family Wnt family ligands Wnt family WNT WFDC WAP four-disulfide core domain containing WFDC WDR WD repeat domain containing WDR UGT UDP glucuronosyltransferases UGT UBXN UBX domain containing UBXN UBOX U-box domain containing UBOX USP Ubiquitin specific peptidases USP Tondu family VGLL Vestigial like family VGLL The VCX/Y genes encode small and highly charged proteins of unknown function. The presence of a putative bipartite nuclear localization signal suggests that VCX/Y members are nuclear proteins. VCX, VCY Variable charge X/Y family VCX, VCY T cell receptors (TR) are antigen receptors of the T cells of the adaptive immune response, acquired by jawed vertebrates (or gnathostomata) more than 450 million years ago and found in all extant jawed vertebrate species from fishes to humans. TR are anchored in the membrane of a T cell as part of the signaling T cell receptor (TcR = TR+CD3). TR alpha/beta recognize processed antigens, which are presented as peptides by the highly polymorphic major histocompatibility (MH, in humans HLA for human leukocyte antigens) proteins, whereas TR gamma/delta recognize nonpeptidic antigens. TR are made of two chains, alpha and beta, or gamma and delta, encoded by genes located in four major loci: the TR alpha (TRA) at 14q11.2, TR beta (TRB) at 7q34, TR gamma (TRG) at 7p14 and TR delta (TRD) at 14q11.2. Genes outside of these major loci are orphons. There are four TR gene types, variable (V), diversity (D) (for TRB and TRD), joining (J) and constant (C) genes which contribute to the TR chain synthesis. The variable domain at the N-terminal end of each TR chain results from a V-(D)-J rearrangement whereas the remaining of the chain, or constant region, is encoded by a C gene. The combinatorial and junctional diversity creates a huge potential diversity of 1012 specific TR per individual, the limiting factor being only the number of T cells that an organism is genetically programmed to produce. T-cell receptors TCRs TR T cell receptors TR The TRA locus at 14q11.2 contains TRAV (variable) genes, TRAJ (joining) genes and one TRAC (constant) gene. TRA T cell receptor alpha locus at 14q11.2 TRA The TRB locus at 7q34 contains TRBV (variable) genes, TRBD (diversity) genes, TRBJ (joining) genes and TRBC (constant) genes. TRB T cell receptor beta locus at 7q34 TRB These are TRB genes that are found outside of the 7q34 TRB locus and therefore cannot form part of a T cell receptor-encoding gene. T cell receptor beta (TRB) orphons The TRD locus at 14q11.2 contains TRDV (variable) genes, TRDD (diversity) genes, TRDJ (joining) genes and one TRDC (constant) gene. TRD T cell receptor delta locus at 14q11.2 TRD The TRG locus at 7p14 contains TRGV (variable) genes, TRGJ (joining) genes and TRGC (constant) genes. TRG T cell receptor gamma locus at 7p14 TRG The Rab family of proteins is a member of the Ras superfamily of monomeric G proteins. Rab GTPases regulate many steps of membrane traffic, including vesicle formation, vesicle movement along actin and tubulin networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface. RAB RAB, member RAS oncogene GTPases RAB The RAS family is a subset of the RAS small GTPase superfamily. The family includes the proto-oncogenes HRAS, NRAS and KRAS. RAS RAS type GTPase family RAS ARPC Actin related protein 2/3 complex subunits ARPC The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic organisms including yeasts and some plants. Three members of the family have been studied a great deal: Cdc42, Rac1, and RhoA. All G proteins are 'molecular switches', and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions. RHO Rho family GTPases RHO RAN RAN family GTPases RAN Mitochondrial Rho proteins (Miro-1, Q8IXI2 [encoded by RHOT1] and Miro-2, Q8IXI1 [encoded by RHOT2]), are atypical Rho GTPases. They have a unique domain organisation, with tandem GTP-binding domains and two EF hand domains (PF00036), that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis. Miro like atypical Rho GTPases RABL RAB like GTPases RABL The ArfGAPs are GTPase activating proteins for the ARF (ADP-ribosylation factor) GTPases. ADP-ribosylation factor GTPase-activating proteins ArfGAPs The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. A kinase (PRKA) anchor proteins A-kinase anchor proteins AKAP A-kinase anchoring proteins AKAP Alcohol dehydrogenases ( ADH ) ( EC 1.1.1.1 ) are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD + to NADH). In humans and many other animals, they serve to break down alcohols that otherwise are toxic, and they also participate in generation of useful aldehyde, ketone, or alcohol groups during biosynthesis of various metabolites. In yeast, plants, and many bacteria, some alcohol dehydrogenases catalyze the opposite reaction as part of fermentation to ensure a constant supply of NAD +. ADH Alcohol dehydrogenases ADH Aldehyde dehydrogenases ( EC 1.2.1.3 ) are a group of enzymes that catalyse the oxidation (dehydrogenation) of aldehydes. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes. ALDH Aldehyde dehydrogenases ALDH AKR Aldo-keto reductases AKR ABHD Abhydrolase domain containing ABHD ACS Acyl-CoA synthetase family ACS Alkaline ceramidases (EC 3.5.1.23) catalyse the following reaction: N-acylsphingosine + H(2)O <=> a carboxylate + sphingosine. ACER Alkaline ceramidases ACER Members of this family are homologous to AlkB, an E.coli enzyme that repairs alkylated DNA and RNA.The 9 human homologs are all members of the alpha-ketoglutarate and FE(II)-dependent dioxygenase superfamily. ALKBH Alkylation repair homologs ALKBH This article refers to the cell-cycle regulatory complex, APC/C. For the tumor suppressor APC, in which mutations lead to colon cancer, see Adenomatous polyposis coli. Anaphase-Promoting Complex (also called the cyclosome or APCC is a large complex of 11-13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C still have unknown functions, but are highly conserved. It was the discovery of the APC/C (and SCF ) and their key role in eukaryotic cell reproduction that established once and for all the importance of ubiquitin -mediated proteolysis in eukaryotic cell biology. Once perceived as a system exclusively involved in removing damaged protein from the cell, ubiquitination and subsequent protein degradation by the proteasome is now perceived as a universal regulatory mechanism for signal transduction whose importance approaches that of protein phosphorylation. In 2014, the APC/C was mapped in 3D at a resolution of less than a nanometre, which also uncovered its secondary structure. Researchers have claimed this finding could transform the understanding of cancer and reveal new binding sites for future cancer drugs. ANAPC Anaphase promoting complex ANAPC Protein containing at least one ANK repeat, a conserved domain of approximately 33 amino acids, that was originally identified in ankyrin. It has been described as an L-shaped structure consisting of a beta-hairpin and two alpha-helices. Many ankyrin repeat regions are known to function as protein-protein interaction domains. ANK repeat containing ANKRD Ankyrin repeat domain containing ANKRD Annexin is a common name for a group of cellular proteins. They are mostly found in eukaryotic organisms (animal, plant and fungi). In humans, the annexins are found inside the cell. However some annexins (Annexin A1, Annexin A2, and Annexin A5) have also been found outside the cellular environment, for example, in blood. How the annexins are transported out of the cell into the blood is a mystery because they lack a signal peptide necessary for proteins to be transported out of the cell. Annexin is also known as lipocortin. Lipocortins suppress phospholipase A2. Increased expression of the gene coding for annexin-1 is one of the mechanisms by which glucocorticoids (such as cortisol ) inhibit inflammation. ANXA Annexins ANXA Protein or apolipoprotein associated with High-Density Lipoproteins (HDL), a class of proteins involved in lipid (cholesterol, phospholipids and triacylglycerol) metabolism in the body fluids. HDL are formed in the liver and are involved in reverse cholesterol transport, the transport of cholesterol from peripherical tissues to the liver. Apolipoproteins are proteins which are specifically associated with lipoproteins, which is not the case for all the proteins associated with HDL or with the other lipoprotein classes. APO Apolipoproteins APO APOBEC ('apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like') is a family of evolutionary conserved proteins. A mechanism of generating protein diversity is mRNA editing. Members of this family are C-to-U editing enzymes. The N-terminal domain of APOBEC like proteins is the catalytic domain, while the C-terminal domain is a pseudocatalytic domain. More specifically, the catalytic domain is a zinc dependent cytidine deaminase domain and is essential for cytidine deamination. RNA editing by APOBEC-1 requires homodimerisation and this complex interacts with RNA binding proteins to form the editosome. APOBEC Apolipoprotein B mRNA editing enzyme catalytic subunits APOBEC Lipoxygenases ( EC 1.13.11.- ) are a family of iron -containing enzymes that catalyse the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure. It catalyses the following reaction: fatty acid + O 2 = fatty acid hydroperoxide Lipoxygenases are found in plants, animals and fungi. Products of lipoxygenases are involved in diverse cell functions. ALOX Arachidonate lipoxygenases ALOX Argonaute/PIWI family Armadillo repeat is the name of a characteristic, repetitive amino acid sequence found in β-catenin and many other proteins, like α-importin, plakoglobin,or adenomatous polyposis coli (APC). Its name derives from the historical name of the β-catenin gene in the fruitfly Drosophila: where they were first discovered. Armadillo repeats are approximately 40 amino acids long and proteins that contain them usually have many tandemly repeated copies. These tandem repeats usually fold together to form a single, rigid protein domain called the armadillo (ARM) domain. Because ARM domains can consist of a variable number of repeats, they are a good example of solenoid protein domains. The best characterized example of armadillo domains is found in β-catenin. β-catenin is a protein involved in linking cadherin cell adhesion proteins to the cytoskeleton, but the Armadillo repeat is found in a wide range of proteins with other functions. This type of protein domain is important in transducing WNT signals during embryonic development. ARM repeat containing ARMC Armadillo repeat containing ARMC ACOT Acyl-CoA hydrolases Acyl-CoA thioesterases ACOT Sulfatases EC 3.1.6. are enzymes of the esterase class that catalyze the hydrolysis of sulfate esters. These may be found on a range of substrates, including steroids, carbohydrates and proteins. Sulfate esters may be formed from various alcohols and amines. In the latter case the resultant N-sulfates can also be termed sulfamates. Sulfatases play important roles in the cycling of sulfur in the environment, in the degradation of sulfated glycosaminoglycans and glycolipids in the lysosome, and in remodelling sulfated glycosaminoglycans in the extracellular space. Together with sulfotransferases, sulfatases form the major catalytic machinery for the synthesis and breakage of sulfate esters. ARS Sulfatases ARS This family page represents various types of ATPases found in human. V-type and F-type ATPases are both rotor protein complexes and are related in structure and function. The V-type ATPase hydrolyses ATP to pump protons across membranes while the F-type ATPase couples proton transfer to synthesis of ATP from ADP. The AAA and P-type families are unrelated and comprise many individual members. The AAA ATPase family hydrolyse ATP to obtain energy for a diverse variety of biological processes. P-type ATPases use the energy from ATP hydrolysis to pump ions across cellular membranes. ATPases AAA or AAA+ is an abbreviation for ATPases Associated with diverse cellular Activities. They share a common conserved module of approximately 230 amino acid residues. This is a large, functionally diverse protein family belonging to the AAA+ superfamily of ring-shaped P-loop NTPases, which exert their activity through the energy-dependent remodeling or translocation of macromolecules. AAA proteins couple chemical energy provided by ATP hydrolysis to conformational changes which are transduced into mechanical force exerted on a macromolecular substrate. AAA proteins are functionally and organizationally diverse, and vary in activity, stability, and mechanism. Members of the AAA family are found in all organisms and they are essential for many cellular functions. They are involved in processes such as DNA replication, protein degradation, membrane fusion, microtubule severing, peroxisome biogenesis, signal transduction and the regulation of gene expression. AAA ATPases (ATPases associated with diverse cellular activities) AAA+ ATPases ATAD ATPase family, AAA domain containing AAA ATPases ATAD The P-type ATPases, also known as E1-E2 ATPases, are a large group of evolutionarily related ion and lipid pumps that are found in bacteria, archaea, and eukaryotes. They are alpha-helical bundle primary transporters referred to as P-type ATPases because they catalyze auto- (or self-) phosphorylation of a key conserved aspartate residue within the pump. In addition, they all appear to interconvert between at least two different conformations, denoted by E1 and E2. Most members of this transporter family are specific for the pumping of a large array of cations, however one subfamily is involved in flipping phospholipids to maintain the asymmetric nature of the biomembrane. Prominent examples of P-type ATPases are the sodium-potassium pump (Na +,K +-ATPase), the plasma membrane proton pump (H +-ATPase), the proton-potassium pump (H +,K +-ATPase), and the calcium pump (Ca 2+ -ATPase). E1-E2 ATPases P-type ATPases Vacuolar-type H +-ATPase ( V-ATPase ) is a highly conserved evolutionarily ancient enzyme with remarkably diverse functions in eukaryotic organisms. V-ATPases acidify a wide array of intracellular organelles and pump protons across the plasma membranes of numerous cell types. V-ATPases couple the energy of ATP hydrolysis to proton transport across intracellular and plasma membranes of eukaryotic cells. ATP6V ATPase H+ transporting subunits Proton pump subunits V-ATPases V-type proton ATPase subunits Vacuolar-type H +-ATPases V-type ATPase subunits ATP6V ATP-binding cassette transporters ( ABC transporters ) are members of a protein superfamily that is one of the largest and most ancient families with representatives in all extant phyla from prokaryotes to humans. ABC transporters are transmembrane proteins that utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to carry out certain biological processes including translocation of various substrates across membranes and non-transport-related processes such as translation of RNA and DNA repair. They transport a wide variety of substrates across extra- and intracellular membranes, including metabolic products, lipids and sterols, and drugs. Proteins are classified as ABC transporters based on the sequence and organization of their ATP-binding cassette (ABC) domain(s). ABC transporters are involved in tumor resistance, cystic fibrosis and a range of other inherited human diseases along with both bacterial (prokaryotic) and eukaryotic (including human) development of resistance to multiple drugs. ABC ABC transporters ABC-type ATPases ATP binding cassette transporters ABC In molecular biology, the ARID domain (AT-rich interaction domain; also known as BRIGHT domain)) is a protein domain that binds to DNA. ARID domain-containing proteins are found in fungi and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene regulation and cell cycle control. Although the specific roles of this domain and of ARID-containing proteins in transcriptional regulation are yet to be elucidated, they include both positive and negative transcriptional regulation and a likely involvement in the modification of chromatin structure. The basic structure of the ARID domain appears to be a series of six alpha-helices separated by beta-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. Based on primary sequence homology, they can be partitioned into three structural classes: Minimal ARID proteins that consist of a core domain formed by six alpha helices; ARID proteins that supplement the core domain with an N-terminal alpha-helix; and Extended-ARID proteins, which contain the core domain and additional alpha-helices at their N- and C-termini. ARID AT rich interactive domain containing AT-rich interaction domain containing ARID The inhibitor of apoptosis domain - also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR - is a structural motif found in proteins with roles in apoptosis, cytokine production, and chromosome segregation. Proteins containing BIR are known as inhibitor of apoptosis proteins (IAPs), or BIR-containing proteins (BIRPs or BIRCs), and include BIRC1 (NAIP), BIRC2 (cIAP1), BIRC3 (cIAP2), BIRC4 (xIAP), BIRC5 (survivin) and BIRC6. BIR domains belong to the zinc-finger domain family and characteristically have a number of invariant amino acid residues, including 3 conserved cysteines and one conserved histidine, which coordinate a zinc ion. They are typically composed of 4-5 alpha helices and a three-stranded beta sheet. BIR repeat containing BIRC Baculovirus inhibitor of apoptosis protein repeat containing IAP repeat containing inhibitor of apoptosis domain containing Baculoviral IAP repeat containing BIRC SCAN is a protein domain frequently found at the N termini of proteins encoded by mammalian tandem zinc finger (ZF) genes, whose structure is known to be similar to that of retroviral gag capsid domains and whose multimerization has been proposed as a model for retroviral assembly. The SCAN domain is derived from the C-terminal portion of the gag capsid (CA) protein from the Gmr1-like family of Gypsy/Ty3-like retrotransposons. SCAN domain containing A basic helix-loop-helix (bHLH) is a protein structural motif that characterizes a family of transcription factors. The motif is characterized by two α-helices connected by a loop. In general, transcription factors including this domain are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding. BHLH Basic helix-loop-helix proteins BHLH BEND BEN domain containing BEND Beta-1,3-glucuronyltransferases (EC 2.4.1.135) catalyse the following reaction: UDP-glucuronate + 3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D-xylosylprotein <=> UDP + 3-beta-D-glucuronosyl-3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D-xylosylprotein. B3GAT Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferases Glucuronosyltransferases, type I Uridine diphosphate glucuronic acid:acceptor glucuronosyltransferases Beta-1,3-glucuronyltransferases B3GAT Enzymes that catalyze the transfer of glycosyl (sugar) residues to an acceptor, both during degradation (cosubstrates= water or inorganic phosphate) and during biosynthesis of polysaccharides, glycoproteins and glycolipids. In biosynthetic glycosyl transfers, the common activated monomeric sugar intermediate is a nucleoside diphosphate sugar. Glycosyltransferases Beta 4-glycosyltransferases GlycosylTransferase Family 31 Beta 3-glycosyltransferases Glycosyl transferases group 1 domain containing Glycosyltransferase family 2 Glycosyltransferase family 6 This functional set of mannosyltransferases all use dolichyl D-mannosyl phosphate (dol-P-Man) as a sugar donor. Dolichyl D-mannosyl phosphate dependent mannosyltransferases EXT Exostosin glycosyltransferase family EXT In enzymology, a polypeptide N-acetylgalactosaminyltransferase ( EC 2.4.1.41 ) is an enzyme that catalyzes the chemical reaction UDP-N-acetyl-D-galactosamine + polypeptide UDP + N-acetyl-D-galactosaminyl-polypeptide Thus, the two substrates of this enzyme are UDP-N-acetyl-D-galactosamine and polypeptide, whereas its two products are UDP and N-acetyl-D-galactosaminyl-polypeptide. This enzyme belongs to the family of glycosyltransferases, specifically the hexosyltransferases. This enzyme participates in o-glycan biosynthesis and glycan structures - biosynthesis 1. It has 2 cofactors : manganese, and calcium. GALNT Polypeptide N-acetylgalactosaminyltransferases GALNT A fucosyltransferase is an enzyme that transfers an L- fucose sugar from a GDP-fucose ( guanosine diphosphate -fucose) donor substrate to an acceptor substrate. The acceptor substrate can be another sugar such as the transfer of a fucose to a core GlcNAc ( N-acetylglucosamine ) sugar as in the case of N-linked glycosylation, or to a protein, as in the case of O -linked glycosylation produced by O -fucosyltransferase. There are various fucosyltransferases in mammals, the vast majority of which, are located in the Golgi apparatus. The O -fucosyltransferases have recently been shown to localize to the endoplasmic reticulum (ER). Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins. Galactoside 3(4)-L-fucosyltransferase ( EC 2.4.1.65 ) belongs to the Lewis blood group system and is associated with Le(a/b) antigen. FUT Fucosyltransferases FUT MGAT Mannosyl-glycoprotein N-acetylglucosaminyltransferases MGAT Glycosyltransferase family 8 Glycogen phosphorylase is one of the phosphorylase enzymes ( EC 2.4.1.1 ). Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. Glycogen phosphorylase is also studied as a model protein regulated by both reversible phosphorylation and allosteric effects. PYG Phosphorylases, glycogen Glycogen phosphorylases PYG Sialyltransferases are a subset of glycosyltransferases that catalyze the transfer of sialic acid (Sia) residues from an activated sugar donor (CMP-βNeu5Ac, CMP-βNeu5Gc, CMP-βKdn) to the hydroxyl group at the terminal non reducing position of Gal, GlcNAc, GalNAc or Sia monosaccharides of glycoconjugate acceptors (glycoproteins or glycolipids) leading to the formation of α2-3, α2-6 or α2-8 glycosidic linkages. Animal sialyltransferases are gathered in a unique group of the CAZy classification (GT#29). Within this group, four families are distinguished based on the glycosidic linkage formed and the monosaccharide acceptor (ST3Gal, ST6Gal, ST6GalNAc and ST8Sia). Sialyltransferases COLGALT Collagen beta(1-O)galactosyltransferases COLGALT UGGT UDP-glucose glycoprotein glucosyltransferases UGGT GCNT, XYLT Glucosaminyl (N-acetyl) transferases/xylosyltransferases GCNT, XYLT Alpha 1,4-glycosyltransferases POGLUT Glycosyltransferase family 90 POGLUT STT3 STT3 oligosaccharyltransferase catalytic subunits STT3 Oligosaccharyltransferase or OST ( EC 2.4.1.119 ) is a membrane protein complex that transfers a 14- sugar oligosaccharide from dolichol to nascent protein. It is a type of glycosyltransferase. The sugar Glc 3Man 9GlcNAc 2 (where Glc= Glucose, Man= Mannose, and GlcNAc= N-acetylglucosamine ) is attached to an asparagine (Asn) residue in the sequence Asn-X- Ser or Asn-X- Thr where X is any amino acid except proline. This sequence is called a glycosylation sequon. The reaction catalyzed by OST is the central step in the N -linked glycosylation pathway. OST OST complex Oligosaccharyltransferase complex subunits OST O-linked N-acetylglucosaminyltransferases Dol-P-Glc:Man(9)GlcNAc(2)-PP-Dol alpha-1->3-glucosyltransferases Dolichyl-P-Glc:Man(9)GlcNAc(2)-PP-dolichol alpha-1,3-glucosyltransferases Alpha-1,3-glucosyltransferases ALG10 Dolichyl-phosphoglucose-dependent glucosyltransferases Alpha-1,2-glucosyltransferases ALG10 UDP-N-acetylglucosaminyltransferase subunits UDP-glucose ceramide glucosyltransferases BLOC-1 or biogenesis of lysosome-related organelles complex 1 is a ubiquitously expressed multisubunit protein complex. BLOC-1 is required for normal biogenesis of specialized organelles of the endosomal -lysosomal system, such as melanosomes and platelet dense granules. BLOC-1 subunits BLOC1S Biogenesis of lysosomal organelles complex 1 subunits BLOC1S Protein belonging to the set of cell surface antigens found chiefly, but not solely, on blood cells. More than fifteen different blood group systems are recognised in humans. In most cases the antigenic determinant resides in the carbohydrate chains of membrane glycoproteins or glycolipids. Blood group antigens Bone morphogenetic proteins ( BMPs ) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signalling in pathological processes. Cancerous disease often involves misregulation of the BMP signalling system. Absence of BMP signalling is, for instance, an important factor in the progression of colon cancer, and conversely, overactivation of BMP signalling following reflux-induced esophagitis provokes Barrett's esophagus and is thus instrumental in the development of adenocarcinoma in the proximal portion of the gastrointestinal tract. BMP Bone morphogenetic proteins BMP BPIF BPI fold containing BPIF The BRICHOS family consists of a variety of proteins linked to major diseases, each containing a 100 amino acid BRICHOS domain that is thought to have a chaperone function. BRICD BRICHOS domain containing BRICD Butyrophilin is a family of proteins. Butyrophilin (Btn) genes constitute a subgroup of at least 10 genes in the Ig superfamily identified in human, mouse, cow, goat and other species. The eponymous Btn gene (BTN1A1 in humans; Btn1a1 in mouse) is highly expressed in the secretory epithelium of the mammary gland during lactation. Other homologues are predominantly expressed in skeletal muscle and the intestine and erythroid cells. In contrast, BTN2A1 and 2 and BTN3A1, 2, and 3 are widely expressed in many tissues, suggesting that the structural domains of Btn proteins may have both universal and tissue-specific functions. BTN Butyrophilins BTN The S-100 proteins (often styled without the hyphen, S100) are a family of low-molecular-weight proteins found in vertebrates and characterized by two calcium-binding sites that have helix-loop-helix ('EF-hand type') conformation. There are at least 21 different S-100 proteins. Their name is derived from the fact that these proteins are soluble in 100%, i.e. saturated ammonium sulfate at neutral pH. They are encoded by a family of genes whose symbols use the S100 prefix, for example, S100A1, S100A2, S100A3. S100 S100 calcium binding proteins S100 AGPAT LPAAT acyl-CoA: 1-acyl-glycerol-3-phosphate acyltransferases lysophosphatidic acid acyltransferases 1-acylglycerol-3-phosphate O-acyltransferases AGPAT The carbonic anhydrases (or carbonate dehydratases ) form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons (or vice versa), a reversible reaction that occurs rather slowly in the absence of a catalyst. The active site of most carbonic anhydrases contains a zinc ion; they are therefore classified as metalloenzymes. One of the functions of the enzyme in animals is to interconvert carbon dioxide and bicarbonate to maintain acid-base balance in blood and other tissues, and to help transport carbon dioxide out of tissues. CA carbonate dehydratases Carbonic anhydrases CA In enzymology, a carboxylesterase or carboxylic-ester hydrolase ( EC 3.1.1.1 ) is an enzyme that catalyzes a chemical reaction of the form a carboxylic ester + H 2O an alcohol + a carboxylate Thus, the two substrates of this enzyme are carboxylic ester and H 2O, whereas its two products are alcohol and carboxylate. CES Carboxylesterases CES Paraoxonases are a group of enzymes involved in the hydrolysis of organophosphates. Arylesterases PON Paraoxonases PON A lipase is an enzyme that catalyzes the hydrolysis of fats (lipids). LIP Lipases LIP AADAC Arylacetamide deacetylase family AADAC PNPLA Patatin like phospholipase domain containing PNPLA A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze: Phospholipase A Phospholipase A1 - cleaves the SN-1 acyl chain. Phospholipase A2 - cleaves the SN-2 acyl chain, releasing arachidonic acid. Phospholipase B - cleaves both SN-1 and SN-2 acyl chains ; this enzyme is also known as a lysophospholipase. Phospholipase C - cleaves before the phosphate, releasing diacylglycerol and a phosphate-containing head group. Phospholipase Cs play a central role in signal transduction, releasing the second messenger inositol triphosphate. Phospholipase D - cleaves after the phosphate, releasing phosphatidic acid and an alcohol. Types C and D are considered phosphodiesterases. Phospholipase A2 acts on the intact lecithin molecule and hydrolyses the fatty acid esterified to the second carbon atom. The resulting products are lysolecithin and a fatty acid. Phospholipase A2 is an enzyme present in the venom of bees and viper snakes. Phospholipases Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis (programmed cell death), necrosis, and inflammation. Caspases are essential in cells for apoptosis, or programmed cell death, in development and most other stages of adult life, and have been termed 'executioner' proteins for their roles in the cell. Some caspases are also required in the immune system for the maturation of lymphocytes. Failure of apoptosis is one of the main contributions to tumour development and autoimmune diseases; this, coupled with the unwanted apoptosis that occurs with ischemia or Alzheimer's disease, has stimulated interest in caspases as potential therapeutic targets since they were discovered in the mid-1990s. CASP cysteine-aspartic proteases cysteine-dependent aspartate-directed proteases peptidase family C14 Caspases CASP CASS Cas family Cas scaffold proteins Cas scaffolding proteins Crk-associated substrate family p130(Cas) family Cas scaffold protein family CASS ADAM ADAM metallopeptidase domain containing ADAM Cathepsins ( Ancient Greek kata- 'down' and hepsein 'boil'; abbreviated CTS ) are proteases ( enzymes that degrades proteins) found in all animals as well as other organisms. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption. Cathepsins have a vital role in mammalian cellular turnover, e.g. bone resorption. They degrade polypeptides and are distinguished by their substrate specificities. CTS Cathepsins CTS The cluster of differentiation (cluster of designation) (often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands (the molecule that activates a receptor) important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD cluster of designation molecules cluster of differentiation molecules CD molecules CD Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. CCN Cyclins CCN A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA (npcRNA), non-messenger RNA (nmRNA) and functional RNA (fRNA). The term small RNA (sRNA) is often used for short bacterial ncRNAs. The DNA sequence from which a non-coding RNA is transcribed is often called an RNA gene. Non-coding RNA genes include highly abundant and functionally important RNAs such as transfer RNA (tRNA) and ribosomal RNA (rRNA), as well as RNAs such as snoRNAs, microRNAs, siRNAs, snRNAs, exRNAs, and piRNAs and the long ncRNAs that include examples such as Xist and HOTAIR (see here for a more complete list of ncRNAs). The number of ncRNAs encoded within the human genome is unknown, however recent transcriptomic and bioinformatic studies suggest the existence of thousands of ncRNAs., but see Since many of the newly identified ncRNAs have not been validated for their function, it is possible that many are non-functional. fRNA functional RNA ncRNA nmRNA non-messenger RNA non-protein-coding RNA npcRNA Non-coding RNAs A microRNA (abbr. miRNA) is a small non-coding RNA molecule (ca. 22 nucleotides ) found in plants, animals, and some viruses, which functions in transcriptional and post-transcriptional regulation of gene expression. Encoded by eukaryotic nuclear DNA in plants and animals and by viral DNA in certain viruses whose genome is based on DNA, miRNAs function via base-pairing with complementary sequences within mRNA molecules. As a result, these mRNA strands are silenced because they can no longer be translated into proteins by ribosomes, and such complexes are often actively disassembled by the cell ('target degradation'). The human genome may encode over 1000 miRNAs, which may target about 60% of mammalian genes and are abundant in many human cell types. MIR MIRN miRNAs MicroRNAs MIR A Transfer RNA (abbreviated tRNA and archaically referred to as sRNA abbreviating soluble RNA) is an adaptor molecule composed of RNA, typically 73 to 94 nucleotides in length, that serves as the physical link between the nucleotide sequence of nucleic acids ( DNA and RNA ) and the amino acid sequence of proteins. It does this by carrying an amino acid to the protein synthetic machinery of a cell ( ribosome ) as directed by a three-nucleotide sequence ( codon ) in a messenger RNA (mRNA). As such, tRNAs are a necessary component of protein translation, the biological synthesis of new proteins according to the genetic code. The specific nucleotide sequence of an mRNA specifies which amino acids are incorporated into the protein product of the gene from which the mRNA is transcribed, and the role of tRNA is to specify which sequence from the genetic code corresponds to which amino acid. One end of the tRNA matches the genetic code in a three-nucleotide sequence called the anticodon. The anticodon forms three base pairs with a codon in mRNA during protein biosynthesis. The mRNA encodes a protein as a series of contiguous codons, each of which is recognized by a particular tRNA. On the other end of the tRNA is a covalent attachment to the amino acid that corresponds to the anticodon sequence. Each type of tRNA molecule can be attached to only one type of amino acid, so each organism has many types of tRNA (in fact, because the genetic code contains multiple codons that specify the same amino acid, there are many tRNA molecules bearing different anticodons which also carry the same amino acid). TR tRNAs Transfer RNAs TR CLK family members have shown to interact with, and phosphorylate, serine / arginine -rich (SR) proteins of the spliceosomal complex, which is a part of the regulatory mechanism that enables the SR proteins to control RNA splicing. CDC-like kinases CLK CLK family LAMMER kinases CDC like kinases CLK CISD NEET protein family CDGSH iron sulfur domain containing CISD CHMP Charged multivesicular body proteins CHMP Chemokines (Greek -kinos, movement) are a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemo tactic cyto kines. Proteins are classified as chemokines according to shared structural characteristics such as small size (they are all approximately 8-10 kilodaltons in size), and the presence of four cysteine residues in conserved locations that are key to forming their 3-dimensional shape. However, these proteins have historically been known under several other names including the SIS family of cytokines, SIG family of cytokines, SCY family of cytokines, Platelet factor-4 superfamily or intercrines. Some chemokines are considered pro- inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Chemokines are found in all vertebrates, some viruses and some bacteria, but none have been described for other invertebrates. Chemokines have been classified into four main subfamilies : CXC, CC, CX3C and XC. All of these proteins exert their biological effects by interacting with G protein -linked transmembrane receptors called chemokine receptors, that are selectively found on the surfaces of their target cells. CCL Chemokines Chemokine ligands CCL Chromatin modifying enzymes JmjC KDM KDM Lysine (K)-specific demethylases histone demethylases Lysine demethylases KDM K(lysine) acetyltransferases KAT Lysine acetyltransferases KAT KMT Lysine (K)-specific methyltransferases Histone lysine methyltransferases KMT Claudins are a family of proteins that are the most important components of the tight junctions, where they establish the paracellular barrier that controls the flow of molecules in the intercellular space between the cells of an epithelium. They have four transmembrane domains, with the N-terminus and the C-terminus in the cytoplasm. CLDN Claudins CLDN CHCHD Coiled-coil-helix-coiled-coil-helix domain containing Mitochondrial CHCHD-containing proteins Mitochondrial coiled-coil-helix-coiled-coil-helix domain containing proteins Twin CX9C motif family Coiled-coil-helix-coiled-coil-helix domain containing proteins CHCHD Protein which contains one or more collagen-like domain. Collagen is a fibrous protein found in vertebrates, the major element of skin, bone, tendon, cartilage, blood vessels and teeth. It forms insoluble fibres of high tensile strength and which contains the unusual amino acids hyroxyproline and hydroxylysine. It is rich in glycine but lacks cysteine and tryptophan, and has an unusually regular amino-acid domain. COL Collagens COL Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca 2+ -dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their function is to bind to oligosaccharide structure or lipids which are on the surface of microorganisms. Like other PRRs they bind pathogen-associated molecular patterns (PAMPs) and also danger-associated molecular patterns (DAMPs) of oligosaccharide origin. Binding of collectins to microorganisms may trigger elimination of microorganisms by aggregation, complement activation, opsonization, activation of phagocytosis or inhibition of microbial growth. Other functions of collectins are modulation of inflammatory, allergic responses, adaptive immune system and clearance of apoptotic cells. COLEC collagen-containing C-type lectins Collectins COLEC The complement system helps or 'complements' the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by the adaptive immune system. The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver, and normally circulating as inactive precursors (pro-proteins). When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Over 30 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. They account for about 5% of the globulin fraction of blood serum and can serve as opsonins. Complement system COG Components of oligomeric golgi complex COG Coronin is an actin binding protein which also interacts with microtubules and in some cell types is associated with phagocytosis. Coronin proteins are expressed in a large number of eukaryotic organisms from yeast to man. CORO Coronins CORO Cyclin-dependent kinases (CDKs) are a family of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is PX, where S/T* is the phosphorylated serine or threonine, P is proline, X is any amino acid, K is lysine, and R is arginine CDK Cyclin dependent kinases CDK Cytochrome b561 is an integral membrane protein responsible for electron transport, binding two heme groups non-covalently. It is a family of ascorbate -dependent oxidoreductase enzymes. CYB561 Cytochrome b561 CYB561 DCAF DDB1 and CUL4 associated factors DCAF DEAD box proteins are involved in an assortment of metabolic processes that typically involve RNAs, but in some cases also other nucleic acids. They are highly conserved in nine motifs and can be found in both prokaryotes and eukaryotes, but not all. Many organisms, including humans, contain DEAD-box helicases, which are involved in RNA metabolism. DDX DEAD box polypeptides DEAD-box helicases DDX ADAMTS ADAM metallopeptidases with thrombospondin type 1 motif ADAMTS DEAH box polypeptides DHX DEAH-box helicases DHX Families of microbicidal and cytotoxic peptides. Defensins have antibacterial, antifungal and antiviral properties. Defensins kills cells by forming voltage-regulated multimeric channels in the susceptible cell's membrane. Defensins Alpha defensins are a family of mammalian defensin peptides. Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide bonding, mammalian defensins are classified into alpha, beta and theta categories. Alpha-defensins, which have been identified in humans, monkeys and several rodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine. DEFA Defensins, alpha DEFA Beta defensins are a family of mammalian defensins. The beta defensins are antimicrobial peptides implicated in the resistance of epithelial surfaces to microbial colonization. Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide bonding, mammalian defensins are classified into alpha, beta and theta categories. Every mammalian species explored thus far has beta-defensins. In cows, as many as 13 beta-defensins exist in neutrophils. However, in other species, beta-defensins are more often produced by epithelial cells lining various organs (e.g. the epidermis, bronchial tree and genitourinary tract. Human, rabbit and guinea-pig beta-defensins, as well as human beta-defensin-2 (hBD2), induce the activation and degranulation of mast cells, resulting in the release of histamine and prostaglandin D2. Beta defensins DEFB Defensins, beta DEFB DENN/MADD domain containing DENND DENN domain containing DENND DVL Dishevelled homologs Dishevelled segment polarity proteins DVL The Basic Leucine Zipper Domain ( bZIP domain ) is found in many DNA binding eukaryotic proteins. One part of the domain contains a region that mediates sequence specific DNA binding properties and the leucine zipper that is required to hold together (dimerize) two DNA binding regions. The DNA binding region comprises a number of basic amino acids such as arginine and lysine. Proteins containing this domain are transcription factors. bZIP domain containing Basic leucine zipper proteins FOX (Forkhead box) proteins are a family of transcription factors that play important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation, and longevity. Many FOX proteins are important to embryonic development. FOX proteins also have pioneering transcription activity by being able to bind condensed chromatin during cell differentiation processes. The defining feature of FOX proteins is the forkhead box, a sequence of 80 to 100 amino acids forming a motif that binds to DNA. This forkhead motif is also known as the winged helix due to the butterfly-like appearance of the loops in the protein structure of the domain. Forkhead genes are a subgroup of the helix-turn-helix class of proteins. FOX Forkhead boxes FOX High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair. HMG High mobility group HMG Canonical high mobility group Non-canonical high mobility group Protein which contains at least one homeobox, a conserved sequence originally detected, on the nucleotide level, in many of the genes which give rise to homeotic and segmentation mutants in Drosophila. The homeobox, also termed homeodomain, consists of about 60 amino acids and is involved in DNA-binding. Homeodomain containing Homeoboxes ANTP class homeoboxes HOXL subclass homeoboxes NKL subclass homeoboxes and pseudogenes PRD class homeoboxes and pseudogenes LIM class homeoboxes POU POU class homeoboxes and pseudogenes POU HNF class homeoboxes SIX SIX family Sine oculis homeobox homologs SINE class homeoboxes SIX TALE class homeoboxes and pseudogenes CUT class homeoboxes and pseudogenes PROX PROS class homeoboxes PROX ZF class homeoboxes and pseudogenes The adenylate cyclases break ATP down into 3',5'-cyclic AMP and diphosphate. 3',5'-cyclic AMP synthetases ADCY ATP pyrophosphate-lyases Adenyl cyclases Adenylyl cyclases Adenylate cyclases ADCY CERS LASS homeoboxes CERS class homeoboxes CERS Myb/SANT domain containing The CENPB family is derived from the tcl/mariner/pogo family of DNA transposases. In the case of CENPB, the catalytic transposase domain — the 'DDE motif', so-called because of the three conserved amino acids that are vital for its exonuclease functionality — has been mutated such as to be theoretically nonfunctional. Other family members likewise lack the catalytic DDE motif. CENP-B family Centromere-Associated Protein B Homologs Helix-turn-helix CENPB type domain containing Helix-turn-helix CENPB type domain family E26 transformation-specific family Helix-turn-helix ETS type domain containing ETS transcription factor family Enzyme that catalyzes DNA synthesis by addition of deoxyribonucleotide units to a DNA chain using DNA as a template. They can also possess exonuclease activity and therefore function in DNA repair. DNA-directed DNA polymerases POL Polymerases, DNA directed DNA polymerases POL Axonemal dyneins come in multiple forms that contain either one, two or three non-identical heavy chains (depending upon the organism and location in the cilium). Each heavy chain has a globular motor domain with a doughnut-shaped structure believed to resemble that of other AAA proteins, a coiled coil 'stalk' that binds to the microtubule, and an extended tail (or 'stem') that attaches to a neighboring microtubule of the same axoneme. Each dynein molecule thus forms a cross-bridge between two adjacent microtubules of the ciliary axoneme. Axonemal dyneins DNA Dyneins, axonemal DNA Dynein is a motor protein (also called molecular motor or motor molecule) in cells which converts the chemical energy contained in ATP into the mechanical energy of movement. Dynein transports various cellular cargo by 'walking' along cytoskeletal microtubules towards the minus-end of the microtubule, which is usually oriented towards the cell center. Thus, they are called 'minus-end directed motors.' This form of transport is known as retrograde transport. In contrast, kinesins, which are motor proteins that move toward the microtubules' plus end, are called plus-end directed motors. Dyneins Cytoplasmic dynein, which has a molecular mass of about 1.5 megadaltons (MDa), contains approximately twelve polypeptide subunits: two identical 'heavy chains', 520 kDa in mass, which contain the ATPase activity and are thus responsible for generating movement along the microtubule; two 74 kDa intermediate chains which are believed to anchor the dynein to its cargo; four 53–59 kDa intermediate chains; and several light chains which are less understood. DYN Dyneins, cytoplasmic DYN ELP Elongator acetyltransferase complex ELP In molecular biology, the EMI domain, first named after its presence in proteins of the EMILIN family, is a small cysteine -rich protein domain of around 75 amino acids. The EMI domain is most often found at the N terminus of metazoan extracellular proteins that are forming or are compatible with multimer formation. It is found in association with other domains, such as C1q, laminin-type EGF-like, collagen-like, FN3, WAP, ZP or FAS1. It has been suggested that the EMI domain could be a protein-protein interaction module, as the EMI domain of EMILIN-1 was found to interact with the C1q domain of EMILIN-2. EMI domain containing Endogenous ligands Endogenous peptides Receptor ligands ELMO (Engulfment and Cell Motility) is a family of related proteins (~82 kDa) involved in intracellular signalling networks. These proteins have no intrinsic catalytic activity and instead function as adaptors which can regulate the activity of other proteins through their ability to mediate protein-protein interactions. ELMO Engulfment and cell motility proteins ELMO Enzyme that degrades DNA or RNA by progressively splitting off single nucleotides from one end of the chain. Exonucleases Ephrins also known as ephrin ligands or Eph family receptor interacting proteins are a family of proteins that serve as the ligands of the ephrin receptor. Ephrin receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinases (RTKs). Since ephrin ligands (ephrins) and Eph receptors (Ephs) are both membrane-bound proteins, binding and activation of Ephepherin signaling regulates a variety of biological processes during embryonic development including the guidance of axon growth cones, formation of tissue boundaries, cell migration, and segmentation. Additionally, Eph/epherin signaling has recently been identified to play a critical role in the maintenance of several processes during adulthood including long-term potentiation, angiogenesis, and stem cell differentiation. EFN Eph family receptor interacting proteins Ephrin ligands Ephrins EFN XPO Exportins XPO FANC Fanconi anemia complementation groups FA complementation groups FANC FABP Fatty acid binding protein family FABP Fatty acid hydroxylase domain containing A fatty acid desaturase is an enzyme that removes two hydrogen atoms from a fatty acid, creating a carbon /carbon double bond. FADS Fatty acid desaturases FADS Fibrinogen C domain containing Fibronectin type III domain containing Fibulin (FY-beau-lin) (now known as Fibulin-1 FBLN1 ) is the prototypic member of a multigene family, currently with seven members. Fibulin-1 is a calcium-binding glycoprotein. In vertebrates, fibulin-1 is found in blood and extracellular matrices. In the extracellular matrix, fibulin-1 associates with basement membranes and elastic fibers. The association with these matrix structures is mediated by its ability to interact with numerous extracellular matrix constituents including fibronectin, proteoglycans, laminins and tropoelastin. In blood, fibulin-1 binds to fibrinogen and incorporates into clots. Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. The amino-terminal domain I of fibulin consists of three anaphylatoxin -like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilized by three disulphide bridges in the pattern Cys14, Cys25 and Cys36 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats. FBLN Fibulins FBLN F-box proteins are proteins containing at least one F-box domain. The first identified F-box protein is one of three components of the SCF complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome. F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle. In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA -mediated gene silencing via RNA interference. In human cells, in high-iron condition, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2. The F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. It was first identified in cyclin F. The F-box motif interacts directly with the SCF protein Skp1, and F-box domains commonly exist in proteins in concert with other protein–protein interaction motifs such as leucine-rich repeats and WD repeats, which are thought to mediate interactions with SCF substrates. FBX F-boxes FBX FBXL F-box and leucine rich repeat proteins FBXL FBXW F-box and WD repeat domain containing FBXW IZUMO IZUMO family IZUMO FBXO group members contain F-box domains and may contain other unrelated domains. The word 'other' is to distinguish this subgroup from the other two F-box subgroups: FBXW (members contain F-box domains and WD40 repeats) and FBXL (members contain F-box domains and leucine-rich repeats). FBXO F-boxes other FBXO The [fermitin or] kindlin family of proteins each contain a bipartite FERM domain comprising four subdomains F0, F1, F2, and F3 that show homology with the FERM head (H) domain of the cytoskeletal Talin protein. Kindlins have been linked to Kindler syndrome, leukocyte adhesion deficiency, cancer and other acquired human diseases. They are essential in the organisation of focal adhesions that mediate cell-extracellular matrix junctions and are involved in other cellular compartments that control cell-cell contacts and nucleus functioning. Therefore they are responsible for cell to cell crosstalk via cell-cell contacts and integrin mediated cell adhesion through focal adhesion proteins and as specialised adhesion structures of hematopoietic cells they are also present in podosome's F actin surrounding ring structure. FERMT Kinderlins Kindlins Fermitins FERMT The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory neurotransmitter in the vertebrate central nervous system. There are two classes of GABA receptors: GABA A and GABA B. GABA A receptors are ligand-gated ion channels (also known as ionotropic receptors), whereas GABA B receptors are G protein-coupled receptors (also known as metabotropic receptors ). Gamma-aminobutyric acid (GABA) receptors The GABA A receptor (GABA AR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABA A receptor selectively conducts Cl-ˆ’ through its pore, resulting in hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring. The reversal potential of the GABA A-mediated IPSP in normal solution is -ˆ’70 mV, contrasting the GABA B IPSP. GABA A receptors GABA ARs GABA(A) receptors GABR Gamma-aminobutyric acid (GABA) A receptors Gamma-aminobutyric acid type A receptor subunits GABR Gamma-glutamyl transferase or gamma-glutamyl transpeptidase ( EC 2.3.2.2 ) is an enzyme that transfers gamma-glutamyl functional groups. It is found in many tissues, the most notable one being the liver, and has significance in medicine as a diagnostic marker. GGT catalyzes the transfer of the gamma-glutamyl moiety of glutathione to an acceptor that may be an amino acid, a peptide or water (forming glutamate ). GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione and drug and xenobiotic detoxification. GGT Gamma-glutamyltransferases GGT General transcription factors (GTFs), also known as basal transcriptional factors, are a class of protein transcription factors that bind to specific sites on DNA to activate transcription. GTFs, RNA polymerase, and the mediator multiple protein complex constitute the basic transcriptional apparatus. GTFs are also intimately involved in the process of gene regulation, and most are required for life. GTF General transcription factors GTF GST Soluble glutathione S-transferases GST Glycerol kinase is a phosphotransferase enzyme involved in triglycerides and glycerophospholipids synthesis. Glycerol kinase catalyzes the transfer of a phosphate from ATP to glycerol thus forming glycerol phosphate (ATP + glycerol <=> ADP + sn-glycerol 3-phosphate ). Adipocytes lack glycerol kinase so they cannot metabolize the glycerol produced during triacyl glycerol degradation. This glycerol is instead shuttled to the liver via the blood where it is: GK Glycerol kinases Glycerol kinase family GK Protein containing one or more covalently linked and usually sulfated glycosaminoglycans, (e.g., chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, keratan sulfate). Glycosaminoglycans are polysaccharides made of repeating disaccharides (usually 40-100 times), which consist of uronic acid (or galactose) and hexosamines. Aggrecan, for example, is the major component in articular cartilage. Proteoglycans Syndecans are single transmembrane domain proteins that are thought to act as coreceptors, especially for G protein-coupled receptors. These core proteins carry three to five heparan sulfate and chondroitin sulfate chains, which allow for interaction with a large variety of ligands including fibroblast growth factors, vascular endothelial growth factor, transforming growth factor -beta, fibronectin and antithrombin -1. Interactions between fibronectin and some syndecans can be modulated by the extracellular matrix protein tenascin C. SDC Syndecan heparan sulfate proteoglycans Syndecans SDC Glypicans constitute one of the two major families of heparan sulfate proteoglycans, with the other major family being syndecans. Six glypicans have been identified in mammals, and are referred to as GPC1 through GPC6. GPC Glypicans GPC SLRP SLRPs SLRRs Small leucine rich repeat proteoglycans Lecticans, also known as hyalectans, are a family of proteoglycans (a type protein that is attached to chains of negatively charged polysaccharides ) that are components of the extracellular matrix. There are four members of the lectican family: aggrecan, brevican, neurocan, and versican. Lecticans interact with hyaluronan and tenascin-R to form a ternary complex. Hyalectans Lecticans Hyalectan proteoglycans Collagen proteoglycans GPN GPN-loop GTPases GPN G patch domain containing GPATCH G-patch domain containing GPATCH In molecular biology, a RING (Really Interesting New Gene) finger domain is a protein structural domain of zinc finger type which contains a Cys 3 HisCys 4 amino acid motif which binds two zinc cations. This protein domain contains from 40 to 60 amino acids. Many proteins containing a RING finger play a key role in the ubiquitination pathway. A-boxes RING zinc fingers RNF Zinc fingers, RING (C3HC4)-type zf-RING Ring finger proteins RNF GIMAP GTPases, IMAP GIMAP HAUS HAUS complex HAUS augmin like complex HAUS Heat shock proteins (HSP) are a group of proteins induced by heat shock, the most prominent members of this group are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). Heat shock proteins The 70 kilodalton heat shock proteins ( Hsp70 s) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. The Hsp70s are an important part of the cell's machinery for protein folding, and help to protect cells from stress. HSPA Heat shock 70kDa proteins HSPA In molecular biology, chaperone DnaJ, also known as Hsp40 (heat shock protein 40 kD), is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans. DNAJ DNAJ (HSP40) heat shock proteins DNAJ HSPB Small heat shock proteins HSPB Hsp90 ( heat shock protein 90 ) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs. Heat shock proteins, as a class, are among the most highly expressed cellular proteins across all species. As their name implies, heat shock proteins protect cells when stressed by elevated temperatures. They account for 1-2% of total protein in unstressed cells. However, when cells are heated, the fraction of heat shock proteins increases to 4-€“6% of cellular proteins. HSP90 Heat shock 90kDa proteins HSP90 Chaperonins are proteins that provide favourable conditions for the correct folding of other proteins, thus preventing aggregation. Newly made proteins usually must fold from a linear chain of amino acids into a three-dimensional form. Chaperonins belong to a large class of molecules that assist protein folding, called molecular chaperones. The energy to fold proteins is supplied by adenosine triphosphate (ATP). Chaperonins The major histocompatibility complex ( MHC ) is a set of cell surface molecules encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells (WBCs), which are immune cells, with other leukocytes or body cells. MHC determines compatibility of donors for organ transplant as well as one's susceptibility to an autoimmune disease via crossreacting immunization. HLA Human leukocyte antigens MHC Major histocompatibility complex Histocompatibility complex HLA The immunoglobulin superfamily (IgSF) is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins (also known as antibodies); they all possess a domain known as an immunoglobulin domain or fold. Members of the IgSF include cell surface antigen receptors, co-receptors and co-stimulatory molecules of the immune system, molecules involved in antigen presentation to lymphocytes, cell adhesion molecules, certain cytokine receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. Immunoglobulin superfamily domain containing Ring, B-box, Coiled-Coil proteins (RBCCs) TRIM TRIM E3 ubiquitin ligases TRIMs Tripartite motif containing Tripartite motif family TRIM V-set domains are Ig-like domains resembling the antibody variable domain. V-set domains are found in diverse protein families, including immunoglobulin light and heavy chains; in several T-cell receptors such as CD2 (Cluster of Differentiation 2), CD4, CD80, and CD86; in myelin membrane adhesion molecules; in junction adhesion molecules (JAM); in tyrosine-protein kinase receptors; and in the programmed cell death protein 1 (PD1). V-set domain containing C1-set domains are classical Ig-like domains resembling the antibody constant domain. C1-set domains are found almost exclusively in molecules involved in the immune system. C1-set domain containing C2-set domains, which are Ig-like domains resembling the antibody constant domain. C2-set domains are found primarily in the mammalian T-cell surface antigens CD2 (Cluster of Differentiation 2), CD4 and CD80, as well as in vascular (VCAM) and intercellular (ICAM) cell adhesion molecules. C2-set domain containing I-set domain containing Immunoglobulin like domain containing ATP-dependent nucleosome remodeling complex which slides mononucleosomes to a central position on a DNA template while tightly organizing nucleosomes within arrays. Functions in maintaining genome stability and removes H2AZ from nucleosomes. May play a largely repressive role in gene transcription, blocking H3K79 methylation and restricting transcription to gene units in euchromatin and away from silent regions, such as heterochromatin. Activates the expression of pluripotency factors by facilitating the recruitment of Mediator and Pol II at their promoters. Required for fork maintenance and progression in stalled replication forks. It is recruited to DNA damage sites and the ACTR8 subunit is required for this recruitment. INO80 chromatin remodeling INO80 complex INO80 complex INO80 Importin is a type of protein that moves other protein molecules into the nucleus by binding to a specific recognition sequence, called the nuclear localization signal (NLS). Importin is classified as a karyopherin. Importin has two subunits, importin alpha and importin beta. Members of the importin-beta family can bind and transport cargo by themselves, or can form heterodimers with importin-alpha. IPO Importins IPO Protein of the integrin family of cell surface heterodimeric receptors that mediates dynamic cell-to-cell as well as cell-to-matrix adhesion. Integrins function as mechanochemical sensors and transducers able to change rapidly and reversibly their adhesive functions by modulating their ligand-binding affinity. Each subunit has a large N-terminal extracellular domain followed by a transmembrane domain and a short C-terminal cytoplasmic region. Some subclasses of integrins share a common beta chain while having different alpha chains. ITG Integrins ITG Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as viruses, bacteria, parasites or tumor cells. They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors. IFNs belong to the large class of glycoproteins known as cytokines. Interferons are named after their ability to 'interfere' with viral replication within host cells. IFNs have other functions: they activate immune cells, such as natural killer cells and macrophages ; they increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes ; and they increase the ability of uninfected host cells to resist new infection by virus. Certain symptoms, such as aching muscles and fever, are related to the production of IFNs during infection. IFN Interferons IFN Interferon receptors ZYG11 ZYG11 cell cycle regulator family ZYG11 MARCH MARCHF Membrane associated ring-CH-type fingers MARCHF Interleukins are a group of cytokines (secreted proteins and signaling molecules ) that were first seen to be expressed by white blood cells ( leukocytes ). The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells. Interleukin receptors on astrocytes in the hippocampus are also known to be involved in the development of spatial memories in mice. IL Interleukins IL An interleukin receptor is a cytokine receptor for interleukins. Interleukin receptors Intermediate filaments (IF) are proteins which are primordial components of the cytoskeleton and the nuclear envelope. They generally form filamentous structures 8 to 14 nm wide and intermediate in size between microtubules and microfilaments. This family of protein includes cytokeratins, vimentin, desmin, glial fibrillary acidic protein, neurofilament proteins and nestin. All IF proteins are structurally similar in that they consist of: a central rod domain which is arranged in coiled-coiled alpha-helices, with at least two short characteristic interruptions; an N-terminal non-helical domain (head) of variable length; and an C-terminal domain (tail) which is also non-helical and shows extreme length variation between different IF proteins. Intermediate filaments These proteins are the most diverse among IFs and constitute type I (acidic) and type II (basic) IF proteins. The many isoforms are divided in two groups: epithelial keratins (about 20) in epithelial cells trichocytic keratins (about 13) (hair keratins), which make up hair, nails, horns and reptilian scales. Regardless of the group, keratins are either acidic or basic. Acidic and basic keratins bind each other to form acidic-basic heterodimers and these heterodimers then associate to make a keratin filament. Acidic keratins Keratins (acidic) Type I cytokeratins Type I intermediate filaments Type I keratins Keratins, type I These proteins are the most diverse among IFs and constitute type I (acidic) and type II (basic) IF proteins. The many isoforms are divided in two groups: epithelial keratins (about 20) in epithelial cells (image to right) trichocytic keratins (about 13) (hair keratins), which make up hair, nails, horns and reptilian scales. Regardless of the group, keratins are either acidic or basic. Acidic and basic keratins bind each other to form acidic-basic heterodimers and these heterodimers then associate to make a keratin filament. Basic keratins Keratins (basic) Type II Keratins Type II cytokeratins Type II intermediate filaments Keratins, type II Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies ( Drosophila melanogaster ). PCGF Polycomb group ring fingers PCGF Intermediate filaments Type III Intermediate filaments Type IV Nuclear lamins (not to be confused with laminins ), also known as Class V intermediate filaments, are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope. They are involved in the breakdown and reformation of the nuclear envelope during mitosis, as well as the positioning of nuclear pores. Class V intermediate filaments LMN Type V intermediate filaments Lamins LMN The beaded filament structural proteins are components of the cytoskeleton in the eye lens. BFSP Eye lens beaded filament structural proteins Type VI intermediate filaments Beaded filament structural proteins BFSP IFFO Intermediate filament family orphans IFFO Intraflagellar transport or IFT is a bidirectional motility along axonemal microtubules that is essential for the formation ( ciliogenesis ) and maintenance of most eukaryotic cilia and flagella. It is thought to be required to build all cilia that assemble within a membrane projection from the cell surface. The process of IFT has been best characterized in the biflagellate alga Chlamydomonas reinhardtii as well as the sensory cilia of the nematode Caenorhabditis elegans. It has been suggested based on localization studies that IFT proteins also function outside of cilia. IFT complexes Intraflagellar transport complexes Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein ( KLKB1 ) has no known homologue, while tissue kallikrein-related peptidases ( KLKs ) encode a family of fifteen closely related serine proteases. These genes are localised to chromosome 19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation. KLK Kallikreins KLK Kelch proteins (and Kelch-like proteins) are a widespread group of proteins that contain multiple Kelch motifs. The kelch domain generally occurs as a set of five to seven kelch repeats that form a beta-propeller tertiary structure. Kelch-repeat beta-propellers are generally involved in protein-protein interactions, though the large diversity of domain architectures and limited sequence identity between kelch motifs make characterisation of the kelch superfamily difficult. KLHL Kelch like KLHL KAPs KRTAP Keratin-associated proteins Keratin associated proteins KRTAP Killer-cell immunoglobulin-like receptors (KIRs), are a family of cell surface proteins found on important cells of the immune system called natural killer (NK) cells. They regulate the killing function of these cells by interacting with MHC class I molecules, which are expressed on all cell types. This interaction allows them to detect virally infected cells or tumor cells that have a characteristic low level of Class I MHC on their surface. Most KIRs are inhibitory, meaning that their recognition of MHC suppresses the cytotoxic activity of their NK cell. Only a limited number of KIRs have the ability to activate cells. KIR molecules are highly polymorphic, meaning their gene sequences differ greatly between individuals, so that different individuals possess different arrays/repertoires of KIR genes. KIR Killer cell immunoglobulin-like receptors Killer-cell immunoglobulin-like receptors Killer cell immunoglobulin like receptors KIR KLR Lectin-like receptors NKC Natural killer cell surface proteins Natural killer complex Killer cell lectin like receptors KLR A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule filaments, and are powered by the hydrolysis of ATP (thus kinesins are ATPases ). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo from the centre of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the microtubules' minus end. KIF Kinesins KIF KANK KANK proteins KN motif and ankyrin repeat domain containing KANK The Kruppel-like family of transcription factors (KLFs) are a set of zinc finger DNA-binding proteins that regulate gene expression. KLF Kruppel like factors Kruppel like transcription factors Kruppel-like family KLF transcription factors KLF LARP La ribonucleoprotein domain containing La-related proteins La ribonucleoproteins LARP Laminins are major proteins in the basal lamina (one of the layers of the basement membrane), a protein network foundation for most cells and organs. The laminins are an important and biologically active part of the basal lamina, influencing cell differentiation, migration, and adhesion, as well as phenotype and survival. LAM Laminin subunits LAM LCE Late cornified envelope proteins LCE LTBP Latent transforming growth factor beta binding proteins LTBP The LGALS genes encode soluble lectins that are referred to as the galectins, galactoside-binding lectins or S-type lectins. Galactoside-binding lectins LGALS Lectins, galactoside-binding S-type lectins Galectins LGALS In molecular biology, the AN1-type zinc finger domain, which has a dimetal (zinc)-bound alpha/beta fold. This domain was first identified as a zinc finger at the C terminus of AN1, a ubiquitin-like protein in Xenopus laevis. The AN1-type zinc finger contains six conserved cysteines and two histidines that could potentially coordinate 2 zinc atoms. AN1 zinc fingers AN1-like Zinc fingers ZFAND zf-AN1 Zinc fingers AN1-type ZFAND The leukocyte immunoglobulin-like receptors (LILR) are a family of receptors possessing extracellular immunoglobulin domains. They are also known as CD85, ILTs and LIR, and can exert immunomodulatory effects on a wide range of immune cells. The human genes encoding these receptors are found in a gene cluster at chromosomal region 19q13.4. CD85 receptors ILTs Ig-like transcripts Immunoglobulin-like transcript receptors LILR LIRs Leucocyte Ig-like receptors Leukocyte immunoglobulin-like receptors Leukocyte immunoglobulin like receptors LILR The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids. They share limited regions of sequence homology and a common tertiary structure architecture. This is an eight stranded antiparallel beta-barrel with a repeated + 1 topology enclosing an internal ligand binding site. These proteins are found in gram negative bacteria, vertebrate cells, and invertebrate cells, and in plants. Lipocalins have been associated with many biological processes, among them immune response, pheromone transport, biological prostaglandin synthesis, retinoid binding, and cancer cell interactions. LCN Lipocalins LCN Calycin structural superfamily The low-density lipoprotein receptor gene family codes for a class of structurally related cell surface receptors that fulfill diverse biological functions in different organs, tissues, and cell types. The role that is most commonly associated with this evolutionarily ancient family is cholesterol homeostasis (maintenance of appropriate concentration of cholesterol). In humans, excess cholesterol in the blood is captured by low-density lipoprotein (LDL) and removed by the liver via endocytosis of the LDL receptor. LRP Low density lipoprotein receptors LRP This family of short proteins includes proteins from the NADH-ubiquinone oxidoreductase complex I. The family includes the B14 subunit from bovine NADH-ubiquinone oxidoreductase B14 subunit, and the B22 [NDUFB9] subunit from the human enzyme. The family has been named LYR after a highly conserved tripeptide motif close to the N terminus of these proteins. LYRM LYR motif containing LYRM Maestro family members are all related by homology and all contain HEAT repeats, or regions that are highly similar to HEAT repeats. MROH Maestro family Maestro heat like repeat containing MROH MXD MAX dimerization proteins MXD Metallothionein (MT) is a family of cysteine-rich, low molecular weight (MW ranging from 500 to 14000 Da ) proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological (such as zinc, copper, selenium ) and xenobiotic (such as cadmium, mercury, silver, arsenic ) heavy metals through the thiol group of its cysteine residues, which represents nearly the 30% of its amino acidic residues. MT Metallothioneins MT Mitochondrial respiratory chain complexes ZBED genes originate from domesticated hAT DNA transposons and encode regulatory proteins of diverse function in vertebrates. The 'BED' zinc finger was named after the domesticated Drosophila BEAF and DREF proteins and has the protein signature, Cx2CxnHx3–5[H/C]. BED zinc fingers ZBED Zinc fingers BED-type ZBED Complex I ( EC 1.6.5.3 ) (also referred to as NADH:ubiquinone oxidoreductase or, especially in the context of the human protein, NADH dehydrogenase (ubiquinone) ) is an enzyme of the respiratory chains of myriad organisms from bacteria to humans. It catalyzes the transfer of electrons from NADH to coenzyme Q10 (CoQ10) and, in eukaryotes, it is located in the inner mitochondrial membrane. It is one of the 'entry enzymes' of oxidative phosphorylation in the mitochondria. Complex I subunits Mitochondrial complex I: NADH dehydrogenase (ubiquinone) subunits NADH dehydrogenase (quinone) subunits NADH-quinone oxidoreductase subunits NADH:ubiquinone oxidoreductase subunits Mitochondrial complex I: NADH:ubiquinone oxidoreductase subunits Succinate dehydrogenase or succinate-coenzyme Q reductase (SQR) or respiratory Complex II is an enzyme complex, bound to the inner mitochondrial membrane of mammalian mitochondria and many bacterial cells. It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. In step 6 of the citric acid cycle, SQR catalyzes the oxidation of succinate to fumarate with the reduction of ubiquinone to ubiquinol. This occurs in the inner mitochondrial membrane by coupling the two reactions together. Complex II subunits SDH SQR subunits Succinate-coenzyme Q reductase subunits Mitochondrial complex II: succinate dehydrogenase subunits SDH The coenzyme Q : cytochrome c-oxidoreductase, sometimes called the cytochrome bc 1 complex, and at other times complex III, is the third complex in the electron transport chain ( EC 1.10.2.2 ), playing a critical role in biochemical generation of ATP ( oxidative phosphorylation ). Complex III is a multisubunit transmembrane protein encoded by both the mitochondrial ( cytochrome b ) and the nuclear genomes (all other subunits). Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Coenzyme Q : cytochrome c-oxidoreductase subunits Complex III subunits Cytochrome bc 1 complex subunits UQCR Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits UQCR The enzyme cytochrome c oxidase or Complex IV, EC 1.9.3.1 ) is a large transmembrane protein complex found in bacteria and the mitochondrion of eukaryotes. It is the last enzyme in the respiratory electron transport chain of mitochondria (or bacteria) located in the mitochondrial (or bacterial) membrane. It receives an electron from each of four cytochrome c molecules, and transfers them to one oxygen molecule, converting molecular oxygen to two molecules of water. In the process, it binds four protons from the inner aqueous phase to make water, and in addition translocates four protons across the membrane, helping to establish a transmembrane difference of proton electrochemical potential that the ATP synthase then uses to synthesize ATP. COX, MT-CO Complex IV subunits Mitochondrial complex IV: cytochrome c oxidase subunits COX, MT-CO ATP synthase ( EC 3.6.3.14 ) is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate (ATP). ATP is the most commonly used 'energy currency' of cells from most organisms. It is formed from adenosine diphosphate (ADP) and inorganic phosphate (P i), and needs energy. The overall reaction sequence is: ADP + P = ATP, where ADP and P i are joined together by ATP synthase Energy is often released in the form of hydrogen ions ( H+ ), moving down an electrochemical gradient, such as from the lumen into the stroma of chloroplasts or from the inter-membrane space into the matrix in mitochondria. ATP synthase subunits ATP5, MT-ATP Complex V F-ATPase F-type ATPase F1-ATPase FoF1-ATPase H+-ATPase subunits H+-translocating ATPase subunits Mitochondrial complex V: ATP synthase subunits ATP5, MT-ATP Mitochondrial respiratory chain complex assembly factors MRP Mitoribosome proteins Mitochondrial ribosomal proteins MRP MOB monopolar spindle-one-binder family MOB kinase activators MOB Mucins are a family of high molecular weight, heavily glycosylated proteins ( glycoconjugates ) produced by epithelial tissues in most metazoans. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signalling to forming chemical barriers. They often take an inhibitory role. Some mucins are associated with controlling mineralization, including nacre formation in mollusks, calcification in echinoderms and bone formation in vertebrates. They bind to pathogens as part of the immune system. Overexpression of the mucin proteins, especially MUC1, is associated with many types of cancer. Although some mucins are membrane -bound due to the presence of a hydrophobic membrane-spanning domain that favors retention in the plasma membrane, most mucins are secreted onto mucosal surfaces or secreted to become a component of saliva. MUC mucus glycoproteins Mucins MUC In the field of molecular biology, myocyte enhancer factor-2 ( Mef2 ) proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development. In adult organisms, Mef2 proteins mediate the stress response in some tissues. Mef2 proteins contain both MADS-box and Mef2 DNA-binding domains. MEF2 Myocyte enhancer factor 2 proteins MEF2 The THAP-type zinc finger (consensus: C-x(2,4)-C-x(35,50)-C-x(2)-H) is an ~90-residue domain restricted to animals, which is shared between the THAP family of cellular DNA-binding proteins, and transposases from mobile genomic parasites. THAP1, the prototype of the THAP family, possesses zinc-dependent sequence-specific DNA binding activity and recognizes a consensus DNA target sequence of 11 nucleotides. The THAP-type zinc finger can be found in one or more copies and can be associated with other domains, such as the C2H2-type zinc finger. The structure of the THAP-type zinc finger reveals the presence between the C2CH zinc coordinating residues of a short antiparallel β-sheet interspersed by a long loop-helix-loop insertion. This loop-helix-loop motif has been shown to be essential for the identification of a number of critical residues for DNA recognition. THAP THAP domain containing THAP-type zinc fingers Thanatos and associated proteins THAP domain family THAP Mitogen-activated protein kinases also known as MAP kinases are serinetyrosine-specific protein kinases belonging to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis - among many others. MAP kinases are found in eukaryotes only, but they are fairly diverse and encountered in all animals, fungi and plants, and even in an array of unicellular eukaryotes. MAPK Mitogen-activated protein kinases MAPK Mitogen-activated protein kinase cascade Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK). MAP2K is classified as EC 2.7.12.2. MAP2K Mitogen-activated protein kinase kinases MAP2K MAP kinase kinase kinase (or MAP3K or MEKK ) is a serine/threonine-specific protein kinase which acts upon MAP kinase kinase. MAP3K MEKK Mitogen-activated protein kinase kinase kinases MAP3K Mitogen-activated protein kinase kinase kinase kinase (MAP4K) is a family of proteins involved in cellular signal transduction. MAP4K Mitogen-activated protein kinase kinase kinase kinases MAP4K Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin -based motility. The term was originally used to describe a group of similar ATPases found in striated and smooth muscle cells. Following the discovery by Pollard and Korn of enzymes with myosin-like function in Acanthamoeba castellanii, a large number of divergent myosin genes have been discovered throughout eukaryotes. Thus, although myosin was originally thought to be restricted to muscle cells (hence, 'myo'), there is no single 'myosin' but rather a huge superfamily of genes whose protein products share the basic properties of actin binding, ATP hydrolysis (ATPase enzyme activity), and force transduction. Virtually all eukaryotic cells contain myosin isoforms. Some isoforms have specialized functions in certain cell types (such as muscle), while other isoforms are ubiquitous. The structure and function of myosin is strongly conserved across species, to the extent that rabbit muscle myosin II will bind to actin from an amoeba. Myosin heavy chains Myosin light chains are distinct and have their own properties, distinct from the heavy chains. They are not considered 'myosins' but are components of the macromolecular complexes that make up the functional myosin enzymes. MYL Myosin light chains MYL MYBP Myosin binding proteins MYBP NKAIN Na+/K+ transporting ATPase interacting NKAIN ZC2HC zf-C2HC Zinc fingers C2HC-type ZC2HC N(alpha)-acetyltransferase subunits NAA N-alpha-acetyltransferase subunits NAA Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word 'netr', which means 'one who guides.' Netrins are genetically conserved across nematode worms, fruitflies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin. NTN Netrins NTN NBPF Neuroblastoma breakpoint family NBPF members NBPF NECAB N-terminal EF-hand calcium binding proteins NECAB NOL1/NOP2/Sun domain family NOP2/Sun domain family NSUN NOP2/Sun RNA methyltransferase family NSUN Nuclear factor of activated T-cells ( NFAT ) is a general name applied to a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems. The NFAT transcription factor family consists of five members NFATc1, NFATc2, NFATc3, NFATc4, and NFAT5. NFATc1 through NFATc4 are regulated by calcium signaling. NFAT Nuclear factors of activated T-cells NFAT NLR NLR family NLR The Nudix family is a protein family of phosphohydrolases. Using water-mediated catalysis they break a phosphate bond in their substrate to create two products. There are two components to the Nudix family: the so-called Nudix fold of a beta sheet with alpha helices on each side and the Nudix motif which contains catalytic and metal-binding amino acids. The Nudix motif is GXXXXXEXXXXXXXREUXEEXGU where U is Isoleucine, Leucine, or Valine and X is any amino acid. This forms a short helix which (usually) contains the catalytic amino acids. NUDT Nudix hydrolase family NUDT ORAI ORAI calcium release-activated calcium modulators ORAI OTU OTU family deubiquitinases ovarian tumor domain DUBs ovarian tumor proteases OTU domain containing OTU Oxysterol-binding proteins, or Oxysterol-binding protein related-proteins, or simply ORPs, are evolutionary related proteins involved in sterol synthesis and/or its regulation. These include mammalian oxysterol-binding protein (OSBP), a protein of about 800 amino-acid residues that binds oxysterols (oxygenated derivatives of cholesterol), cholesterol and phosphatidylinositol 4-phosphate (PI4P); yeast Osh1, a protein of 859 residues that plays a role in ergosterol synthesis; and yeast proteins HES1 and KES1, highly related proteins of 434 residues that seem to play a role in ergosterol synthesis ORPs OSBP Oxysterol-binding protein related-proteins Oxysterol-binding proteins Oxysterol binding proteins OSBP The PNMA family of gag-like capsid genes was domesticated from an ancient vertebrate retrotransposon of the Metaviridae clade at least 100 million years ago. PNMA PNMA family Paraneoplastic Ma antigens PNMA The parvins are a family of proteins involved in linking integrins and associated proteins with intracellular pathways that regulate actin cytoskeletal dynamics and cell survival. PARV Parvins PARV PATE PATE family PATE Protein which contains a paired box domain, a conserved domain of about 120 amino acids, which is generally located in the N-terminal section of various proteins. PAX Paired boxes PAX PELI Pellino E3 ubiquitin protein ligases PELI This gene family encodes enzymes that catalyse the following reaction: Protein L-arginine + H(2)O <=> protein L-citrulline + NH(3). E.C. number 3.5.3.15 PADI Peptidyl arginine deiminases PADI Perilipin, also known as lipid droplet-associated protein or PLIN, is a protein that, in humans, is encoded by the PLIN gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphorylation of perilipin is essential for the mobilization of fats in adipose tissue. PLIN Perilipins PLIN PHACTR Phosphatase and actin regulators PHACTR PIG Phosphatidylinositol glycan anchor biosynthesis PIG A phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators of signal transduction mediated by these second messenger molecules. PDE Phosphodiesterases PDE Pleckstrin homology domain (PH domain) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. This domain can bind Phosphatidylinositol lipids within biological membranes (such as Phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (4,5)-bisphosphate ), and proteins such as the Betagamma-subunits of heterotrimeric G proteins, and protein kinase C. Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. PLEKH Pleckstrin homology domain containing PLEKH A plexin is a protein which acts as a receptor for semaphorin. Plexin acts as a signal transduction molecule in the neuropilin-plexin receptor complex. Plexins also act as transduction factors for ITAM-DAP12-RANKL signalling pathway involved in osteoclastic differentiation. PLXN Plexins PLXN Poly (ADP-ribose) polymerase ( PARP ) is a family of proteins involved in a number of cellular processes involving mainly DNA repair and programmed cell death. ADP-ribosyl-transferases diphtheria toxin-like family ARTD family PARP Poly (ADP-ribose) polymerases Poly-(ADP-ribose) polymerases Poly(ADP-ribose) polymerases PARP CT antigen 104 family POTE prostate, ovary, testis and placenta expressed ankyrin domain containing POTE ankyrin domain containing POTE PRAMEF PRAME family PRAMEF PTAR Prenyltransferase alpha subunit repeat containing PTAR Also known as the Proteasome endopeptidase complex (EC 3.4.25.1). The complex is ATP-dependent and cleaves a wide range of peptide bonds. Macropain PSM Prosome Proteasome endopeptidase complex subunits Proteasome subunits Proteasome PSM Protein disulfide isomerase or PDI is an enzyme in the endoplasmic reticulum in eukaryotes that catalyzes the formation and breakage of disulfide bonds between cysteine residues within proteins as they fold. PDI Protein disulfide isomerases PDI This family of enzymes removes phosphate groups from serine/threonine residues of proteins, thus reversing the action of serine/threonine kinase enzymes. The enzymes listed here are related by homology and most require regulatory subunits to function. PPP Protein phosphatases, catalytic subunits Protein phosphatase catalytic subunits PPP PPP1R subunits (also known as PP1-interacting proteins, or PIPs) direct the substrate specificity of protein phosphatase 1 catalytic (PPP1C) subunits. The large number of PPP1Rs reflects the wide substrate range of the serine/threonine phosphatase holoenzymes. PIPs PP1-interacting proteins PPP1R Protein phosphatase 1 regulatory subunits PPP1R PPP2R subunits direct the substrate specificity of protein phosphatase 2 catalytic (PPP2C) subunits. PPP2R Protein phosphatase 2 regulatory subunits PPP2R PPP3R subunits direct the substrate specificity of protein phosphatase 3 catalytic (PPP3C) subunits. PPP3R Protein phosphatase 3 regulatory subunits PPP3R PPP4R subunits direct the substrate specificity of the protein phosphatase 4 catalytic (PPP4C) subunit. PPP4R Protein phosphatase 4 regulatory subunits PPP4R PPP6R subunits direct the substrate specificity of the protein phosphatase 6 catalytic (PPP6C) subunit. PPP6R Protein phosphatase 6 regulatory subunits PPP6R The PPM family, which includes PP2C [PPM1] and pyruvate dehydrogenase phosphatase, are enzymes with Mn2+/Mg2+ metal ions that are resistant to classic inhibitors and toxins of the PPP family. PP2C phosphatase family PPM Type 2C protein phosphatases Protein phosphatases, Mg2+/Mn2+ dependent PPM The HAD phosphatase family are named after the bacterial enzyme haloacid dehydrogenase and employ an Asp-based catalytic mechanism. This family represents HAD Asp-based protein phosphatases. Class IV: Asp-based DSPs HAD Asp-based protein phosphatases A protein phosphatase is an enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein. Protein phosphatases Class I phosphatases are grouped into the dual specificity phosphatases that can dephosphorylate tyrosine residues and also serine/threonine residues, and the protein tyrosine phosphatases that are subdivided into receptor and non-receptor types, which can dephosphorylate only tyrosine residues. Class I classical Cys-based phosphatases In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules. In response, these receptors work with other proteins to regulate the expression of specific genes, thereby controlling the development, homeostasis, and metabolism of the organism. Nuclear receptors have the ability to directly bind to DNA and regulate the expression of adjacent genes, hence these receptors are classified as transcription factors. The regulation of gene expression by nuclear receptors generally only happens when a ligand - a molecule that affects the receptor's behavior - is present. More specifically, ligand binding to a nuclear receptor results in a conformational change in the receptor, which, in turn, activates the receptor, resulting in up-regulation or down-regulation of gene expression. A unique property of nuclear receptors that differentiates them from other classes of receptors is their ability to directly interact with and control the expression of genomic DNA. As a consequence, nuclear receptors play key roles in both embryonic development and adult homeostasis. As discussed below, nuclear receptors may be classified according to either mechanism or homology. NR Zinc fingers, C4-type Nuclear hormone receptors NR Dual-specificity phosphatase is a form of phosphatase that can act upon tyrosine or serine / threonine residues. All [DUSPs] share a similar catalytic mechanism, by which a conserved cysteine residue forms a covalent intermediate with the phosphate group to be eliminated. The residues surrounding their calatytic core obey a rather strict consensus: His-Cys-x-x-x-x-x-Arg-Ser. The serine side chain and an additional conserved aspartate play a central role in the elimination of the Cys-linked intermediate, thus completing their enzymatic cycle. The main difference between tyrosine-specific phosphatases and dual-specificity phosphatases lies in the width of the latter enzymes' catalytic pocket: thus they can accommodate phosphorylated serine or threonine side chains as well as phosphorylated tyrosines. Class I dual specificity Cys-based phosphatases DUSP Dual specificity phosphatases DUSP LMW (low-molecular-weight) phosphatases, or acid phosphatases, act on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. The class II PTPs contain only one member, low-molecular-weight phosphotyrosine phosphatase (LMPTP). Class II Cys-based phosphatases CDC25 CDC25 phosphatases family Cell division cycle 25 phosphatases Class III Cys-based phosphatases Class III Cys-based CDC25 phosphatases CDC25 At either end of the X and Y chromosomes are homologous regions known as the pseudoautosomal regions (PARs). These two regions pair regularly at male meiosis and undergo recombination. PAR1 is at the tip of the short 'p' arms (Xp22 and Yp11) and PAR2 is at the tip of the long 'q' arms (Xq28 and Yq12). There has been a report of a third pseudoautosomal region (PAR3), but this remains uncorroborated (PMID: 23708688). Pseudoautosomal regions PAR1 Pseudoautosomal region 1 PAR1 PAR2 Pseudoautosomal region 2 PAR2 REEP REEP family Receptor accessory proteins REEP RAMP Receptor (G protein-coupled) activity modifying proteins RAMP RTP Receptor transporter proteins RTP RGS are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. RGS Regulators of G-protein signaling RGS Rho GTPase activating proteins (RhoGAPs or ARHGAPs) bind to and stimulate the GTPase activity of Rho family small GTPases. ARHGAP Rho GTPase activating proteins ARHGAP Rho guanine nucleotide exchange factors (RhoGEFs or ARHGEFs) activate Rho family small GTPases by catalysing the exchange of GDP for GTP. ARHGEF Dbl family Rho guanine nucleotide exchange factors Dbl like Rho GEFs Dbl family Rho GEFs ARHGEF Ribonuclease A (RNase A) is a pancreatic ribonuclease that cleaves single-stranded RNA. RNASE Ribonuclease A family RNASE RBM RRM containing RNA binding motif containing RBM RNA polymerase (RNAP or RNApol), also known as DNA-dependent RNA polymerase, is an enzyme that produces primary transcript RNA. DNA-dependent RNA polymerase subunits DNA-directed RNA polymerase subunits POLR RNA polymerase subunits POLR RPUSD RNA pseudouridylate synthase domain containing RPUSD RPS S ribosomal proteins RPS RPL L ribosomal proteins RPL Zinc finger proteins are generally thought of as DNA-binding transcription factors. However, certain classes of zinc finger proteins, such as CCCH zinc finger proteins, often function as RNA-binding proteins and regulate RNA metabolism. CCCH zinc finger proteins are characterized by one or more CCCH zinc finger domains containing three cysteines and a histidine. Although the functions of most CCCH zinc finger proteins remain obscure, emerging evidence suggests that some CCCH zinc finger proteins are involved in a broad range of biological processes that are associated with immune responses, including cytokine production, immune cell activation, immune homeostasis and antiviral innate immunity, as well as in regulation of cell differentiation and cancer cell growth. C3H type zinc fingers ZC3H zf-CCCH Zinc fingers CCCH-type ZC3H SASH SAM and SH3 domain containing SASH Septins are a group of highly conserved GTP binding proteins found in eukaryotes. In yeast cells, they build scaffolding to provide structural support during cell division and compartmentalize parts of the cell. Recent research in human cells suggests that septins build cages around bacterial pathogens, immobilizing the harmful microbes and preventing them from invading other cells. SEPT SEPTIN Septins SEPTIN The Secreted frizzled-related protein (SFRP) family consists of five secreted glycoproteins in humans (SFRP1, SFRP2, SFRP3 [FRZB], SFRP4, SFRP5) that act as extracellular signaling ligands. Each SFRP is around 300 amino acids in length and contains a cysteine-rich domain (CRD) that shares 30-50% sequence homology with the CRD of Frizzled (Fz) receptors. SFRPs are able to bind Wnt proteins and Fz receptors in the extracellular compartment. SFRP Secreted frizzled-related proteins SFRP SCGB Secretoglobins SCGB SCAMP Secretory carrier membrane proteins SCAMP Semaphorins are a class of secreted and membrane proteins that act as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor complexes. SEMA Semaphorins SEMA SR proteins SRSF Serine/arginine-rich splicing factors Serine and arginine rich splicing factors SRSF Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the (enzyme's) active site. PRSS Proteases, serine Serine endopeptidases Serine peptidases Serine proteases PRSS Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases (serine protease inhibitors). SERPIN Serine (or cysteine) peptidase inhibitors Serpin peptidase inhibitors SERPIN This fold group is defined by two short β-strands connected by a turn (zinc knuckle) followed by a short helix or loop and resembles the classical Cys2His2 motif with a large portion of the helix and β-hairpin truncated. ZCCHC zf-CCHC zinc knuckle containing Zinc fingers CCHC-type ZCCHC SPINK Serine peptidase inhibitors, Kazal type SPINK SH2 domain containing SHISA Shisa family members SHISA The short-chain dehydrogenases/reductases family (SDR) is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. SDR SDR family Short chain dehydrogenase/reductase superfamily SDR Siglecs (Sialic acid-binding immunoglobulin-type lectins) are cell surface proteins that bind sialic acid. They are found primarily on the surface of immune cells and are a subset of the I-type lectins. There are 14 different mammalian Siglecs, providing an array of different functions based on cell surface receptor-ligand interactions. SIGLECs Sialic acid binding Ig-like lectins Sialic acid binding immunoglobulin superfamily lectins Sialic acid-binding immunoglobulin-type lectins Sialic acid binding Ig like lectins SIGLECs SLC56 Sideroflexins SLC56, SFXN Sideroflexin family Sideroflexins Solute carrier family 56 Solute carrier family 56, sideroflexins SLC56, SFXN SIRP Signal regulatory proteins SIRP SKI transcriptional corepressors DBF4 contains an N-terminal BRCT domain and a C-terminal conserved region that could potentially coordinate one zinc atom, the DBF4-type zinc finger... which is important for the interaction with Cdc7 (<a href='https://pubmed.ncbi.nlm.nih.gov/8943332/'>PMID: 8943332</a>, <a href='https://pubmed.ncbi.nlm.nih.gov/8066465/'>PMID: 8066465</a>). DBF zinc fingers ZDBF zf-DBF Zinc fingers DBF-type ZDBF SMADs are intracellular proteins that transduce extracellular signals from transforming growth factor beta ligands to the nucleus where they activate downstream gene transcription. Mother against Dpp (MAD) homology (MH) domain transcription factors SMAD SMAD family SMAD SGSM Small G protein signaling modulators SGSM The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. SLC Solute carrier families SLC Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain (a phospholipid-binding motif) or through protein-protein interactions with membrane-associated protein complexes. Some members of this family have been shown to facilitate protein sorting. SNX Sorting nexins SNX SP Specificity protein transcription factors Sp transcription factors SP SPDY Speedy homologs Speedy/RINGO cell cycle regulator family SPDY SOX genes encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homologous sequence called the HMG-box (for high mobility group ). This HMG box is a DNA binding domain that is highly conserved throughout eukaryotic species. Homologues have been identified in insects, nematodes, amphibians, reptiles, birds and a range of mammals. However, HMG boxes can be very diverse in nature, with only a few amino acids being conserved between species. Sox genes are defined as containing the HMG box of a gene involved in sex determination called SRY, which resides on the Y-chromosome (Sox stands for Sry-related HMG box). There are 20 SOX genes present in humans and mice, and 8 present in Drosophila. Almost all Sox genes show at least 50% amino acid similarity with the HMG box in Sry. The family is divided into subgroups according to homology within the HMG domain and other structural motifs, as well as according to functional assays. SOX Sex determining region Y boxes Sox family Sry-related HMG boxes SRY-box transcription factors SOX STARD START domain containing StAR related lipid transfer domain containing STARD DHHC palmitoyltransferase domain containing DHHC-PATs DHHC-type acyltransferases PATs Palmitoyltransferases Protein acyl transferases ZDHHC zDHHC palmitoyltransferases zf-DHHC Zinc fingers DHHC-type ZDHHC SAM domain containing SAMD Sterile alpha motif domain containing SAMD SMC proteins represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes. SMC Structural maintenance of chromosomes proteins SMC SULT Sulfotransferases, cytosolic SULT Sulfotransferases EC 2.8.2. are transferase enzymes that catalyze the transfer of a sulfo group (not a sulfate group) from a donor molecule to an acceptor alcohol or amine. The most common sulfo group donor is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In the case of alcohol as acceptor, the product is a sulfate (R-OSO3-), whereas an amine leads to a sulfo-amine (R-NH-SO3-). Both reactive groups for a sulfonation via sulfotransferases may be part of a protein, lipid, carbohydrate or steroid. Sulfotransferases, membrane bound SOCS (suppressor of cytokine signaling proteins) refers to a family of genes involved in inhibiting the JAK-STAT signaling pathway. SOCS Suppressors of cytokine signaling SOCS SYT Synaptotagmins SYT T-boxes TBX T-box transcription factors TBX TCTN Tectonic proteins TCTN Tetraspanins, also called tetraspans or the transmembrane 4 superfamily (TM4SF), have four transmembrane domains, intracellular N- and C-termini and two extracellular domains, one short (called the small extracellular domain or loop, SED/SEL or EC1) and one longer, typically 100 amino acid residues (the large extracellular domain/loop, LED/LEL or EC2). TM4SF TSPAN Tetraspans Transmembrane 4 superfamily Tetraspanins TSPAN TPR TTC Tetratricopeptide repeat domain containing TTC THOC THO complex THOC TRAPP complex TRAPPC Transport protein particle complex Trafficking protein particle complex subunits TRAPPC A transglutaminase is an enzyme that catalyzes the formation of an isopeptide bond between a free amine group (e.g., protein- or peptide-bound lysine ) and the acyl group at the end of the side chain of protein - or peptide -bound glutamine. The reaction also produces a molecule of ammonia. Such an enzyme is classified as EC 2.3.2.13. Bonds formed by transglutaminase exhibit high resistance to proteolytic degradation (proteolysis). TGM Transglutaminases TGM TMCC Transmembrane and coiled-coil domain containing TMCC TSEN tRNA-splicing endonuclease subunits TSEN Tropomyosins are a large family of integral components of actin filaments that play a critical role in regulating the function of actin filaments in both muscle and nonmuscle cells. These proteins consist of rod-shaped coiled-coil hetero- or homo-dimers that lie along the α-helical groove of most actin filaments. Interaction occurs along the length of the actin filament, with dimers aligning in a head-to-tail fashion. TPM Tropomyosins TPM Tubulin (tubul- + -in) is one of several members of a small family of globular proteins. The tubulin superfamily includes five distinct families, the alpha-, beta-, gamma-, delta-, and epsilon-tubulins and a sixth family (zeta-tubulin) which is present only in kinetoplastid protozoa. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55,000 Daltons. Microtubules are assembled from dimers of α- and β-tubulin. These subunits are slightly acidic with an isoelectric point between 5.2 and 5.8. TUB Tubulins TUB TTL Tubulin tyrosine ligase family TTL TDRD Tudor domain containing TDRD Tumor necrosis factors (or the TNF family) refer to a group of cytokines that can cause cell death (apoptosis). TNFSF Tumor necrosis factor (ligand) superfamily Tumor necrosis factor superfamily TNFSF A tumor necrosis factor receptor (TNFR), or death receptor, is a trimeric cytokine receptor that binds tumor necrosis factors (TNF). TNFRSF death receptors Tumor necrosis factor receptor superfamily TNFRSF Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and thus are thought to functionally link the ubiquitination machinery to the proteasome to effect in vivo protein degradation. UBQLN Ubiquilin family UBQLN UBR Ubiquitin protein ligase E3 component n-recognins UBR Long non-coding RNAs are defined as any genes that produce transcripts of over 200 nucleotides in length which do not appear to be translated. Wherever possible, the HGNC names these genes based on a key function or characteristic of the encoded RNA. Where no other information is available at the time of naming, we assign a systematic nomenclature as shown in the gene subgroups below. Large noncoding RNAs Long non coding RNAs lncRNAs long ncRNAs Long non-coding RNAs Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a 'stalk' motif containing a GPCR proteolytic site. The N-terminus often shares structural homology with proteins such as lectins and immunoglobulins, leading to the term adhesion GPCR. ADGR Adhesion G protein-coupled receptors ADGR There are four major zona pellucida glycoproteins, termed ZP1-4. ZP1, ZP3 and ZP4 bind to capacitated spermatozoa and induce the acrosome reaction. Successful fertilization depends on the ability of sperm to penetrate the extracellular matrix that surrounds the egg. ZP Zona pellucida glycoproteins ZP ABCA ATP-binding cassette, sub-family A (ABC1) ATP binding cassette subfamily A ABCA ABCB ATP-binding cassette, sub-family B (MDR/TAP) ATP binding cassette subfamily B ABCB ABCC ATP-binding cassette, sub-family C (CFTR/MRP) ATP binding cassette subfamily C ABCC ABCD ATP binding cassette subfamily D ABCD ABCE ATP binding cassette subfamily E ABCE The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two zinc ions. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. FYVE-type domains are divided into two known classes: FYVE domains that specifically bind to phosphatidylinositol 3-phosphate in lipid bilayers and FYVE-related domains of undetermined function. FYVE domain containing ZFYVE Zinc fingers FYVE-type ZFYVE ABCF ATP-binding cassette, sub-family F (GCN20) ATP binding cassette subfamily F ABCF ABCG ATP-binding cassette, sub-family G (WHITE) ATP binding cassette subfamily G ABCG PTPN Protein tyrosine phosphatases non-receptor type PTPN PTPR Protein tyrosine phosphatases receptor type PTPR Serine/threonine phosphatases Chitinases (EC 3.2.1.14, chitodextrinase, 1,4-beta-poly-N-acetylglucosaminidase, poly-beta-glucosaminidase, beta-1,4-poly-N-acetyl glucosamidinase, poly glycanohydrolase, (1->4)-2-acetamido-2-deoxy-beta-D-glucan glycanohydrolase) are hydrolytic enzymes that break down glycosidic bonds in chitin. As chitin is a component of the cell walls of fungi and exoskeletal elements of some animals (including worms and arthropods), chitinases are generally found in organisms that either need to reshape their own chitin or dissolve and digest the chitin of fungi or animals. CHI Glycoside Hydrolase Family 18 Chitinases CHI The exosome complex (or PM/Scl complex, often just called the exosome) is a multi-protein complex capable of degrading various types of RNA (ribonucleic acid) molecules. Exosome complexes are found in both eukaryotic cells and archaea, while in bacteria a simpler complex called the degradosome carries out similar functions. The core of the exosome contains a six-membered ring structure to which other proteins are attached. In eukaryotic cells, the exosome complex is present in the cytoplasm, nucleus and especially the nucleolus, although different proteins interact with the exosome complex in these compartments regulating the RNA degradation activity of the complex to substrates specific to these cell compartments. Substrates of the exosome include messenger RNA, ribosomal RNA, and many species of small RNAs. The exosome has an exoribonucleolytic function, meaning it degrades RNA starting at one end (the 3′ end in this case), and in eukaryotes also an endoribonucleolytic function, meaning it cleaves RNA at sites within the molecule. Several proteins in the exosome are the target of autoantibodies in patients with specific autoimmune diseases (especially the PM/Scl overlap syndrome ) and some antimetabolitic chemotherapies for cancer function by blocking the activity of the exosome. In addition, mutations in exosome component 3 cause pontocerebellar hypoplasia and spinal motor neuron disease. EXOSC PM/Scl complex Exosome complex EXOSC Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis. STX Syntaxins STX Guanylate cyclase ( EC 4.6.1.2, also known as guanylyl cyclase, guanyl cyclase, or GC) is a lyase enzyme. GCs GUCY Guanyl cyclases Receptor guanylyl cyclase (RGC) family Guanylate cyclases GUCY In molecular biology, GATA zinc fingers are zinc-containing domains found in a number of transcription factors (including erythroid-specific transcription factor and nitrogen regulatory proteins). Some members of this class of zinc fingers specifically bind the DNA sequence (A/T)GATA(A/G) in the regulatory regions of genes., giving rise to the name of the domain. In these domains, a single zinc ion is coordinated by 4 cysteine residues. NMR studies have shown the core of the Znf to comprise 2 irregular anti-parallel beta-sheets and an alpha-helix, followed by a long loop to the C-terminal end of the finger. The N-terminal part, which includes the helix, is similar in structure, but not sequence, to the N-terminal zinc module of the glucocorticoid receptor DNA-binding domain. The helix and the loop connecting the 2 beta-sheets interact with the major groove of the DNA, while the C-terminal tail wraps around into the minor groove. Interactions between the Znf and DNA are mainly hydrophobic, explaining the preponderance of thymines in the binding site; a large number of interactions with the phosphate backbone have also been observed. Two GATA zinc fingers are found in GATA-family transcription factors. However, there are several proteins that only contain a single copy of the domain. It is also worth noting that many GATA-type Znfs (such as those found in the proteins GATAD2B and MTA1) have not been experimentally demonstrated to be DNA-binding domains. Furthermore, several GATA-type Znfs have been demonstrated to act as protein-recognition domains. For example, the N-terminal Znf of GATA1 binds specifically to a zinc finger from the transcriptional coregulator FOG1 (ZFPM1). GATAD zinc fingers, GATA-type GATA zinc finger domain containing GATAD Soluble guanylyl cyclase (sGC) is the only known receptor for nitric oxide, NO. It is soluble, i.e. completely intracellular. Most notably, this enzyme is involved in vasodilation. In humans, it is encoded by the genes GUCY1A1, GUCY1A2, GUCY1B2 and GUCY1B3. It is classified under EC number 4.6.1.2. GUCY1 Nitric oxide (NO)-sensitive (soluble) guanylyl cyclases Soluble guanylyl cyclases Type II soluble GC receptors sGC receptors sGCs Soluble guanylate cyclases GUCY1 Sulfotransferases (EC 2.8.2.-) are transferase enzymes that catalyze the transfer of a sulfo group (not a sulfate group) from a donor molecule to an acceptor alcohol or amine. The most common sulfo group donor is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). In the case of alcohol as acceptor, the product is a sulfate (R-OSO 3 -), whereas an amine leads to a sulfo-amine (R-NH-SO 3 -). Both reactive groups for a sulfonation via sulfotransferases may be part of a protein, lipid, carbohydrate or steroid. Sulfotransferases This family contains proteins with tandem C-terminal cytoplasmic C2 domains that are similar to those found in synaptotagmins, but the N-terminal parts of the proteins differ from the synaptotagmin family. Synaptotagmin like tandem C2 proteins A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. The typical version (PKC-C2) has a beta-sandwich composed of 8 Beta-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by the first and final loops of the domain, on the membrane binding face. Many other C2 domain families don't have calcium binding activity. C2 domain containing MCTP Multiple C2 and transmembrane domain containing MCTP E-SYT ESYT FAM62 Extended synaptotagmins ESYT FER1L Ferlin family FER1L In molecular biology, copines is a name for the group of human proteins that includes members such as CPNE1, CPNE4, CPNE6, and CPNE8. These are highly conserved, calcium-dependent membrane proteins found in a variety of eukaryotes. The domain structure of these proteins suggests that they may have a role in membrane trafficking in some prokaryotes as well as eukaryotes. CPNE Copines CPNE This group contains genes that encode proteins with a HIT-type zinc finger, which contains 7 conserved cysteines and one histidine that can potentially coordinate two zinc atoms. It has been named after the first protein that originally defined the domain: the yeast HIT1 protein. The HIT-type zinc finger displays some sequence similarities to the MYND-type zinc finger. The function of this domain is unknown but it is mainly found in nuclear proteins involved in gene regulation and chromatin remodeling. HIT zinc fingers ZNHIT zf-HIT Zinc fingers HIT-type ZNHIT C2 and RasGAP domain containing Phosphatidylinositol-4,5-bisphosphate 3-kinase (also called phosphatidylinositide 3-kinases, phosphatidylinositol-3-kinases, PI 3-kinases, PI(3)Ks, PI-3Ks or by the [HGNC] official stem symbol for the gene family, PI3K(s)) are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor PTEN, is implicated in insensitivity of cancer tumors to insulin and IGF1, in calorie restriction. PI 3-kinases PI(3)Ks PI-3Ks PIK3C Phosphatidylinositol 3-kinase subunits PIK3C C2 domain containing phospholipases RIMS Regulating synaptic membrane exocytosis family RIMS C2 domain containing protein kinases UNC13 UNC13 homologs UNC13 C2 tensin-type domain containing C2 and WW domain containing Genes encoding proteins that contain U1-type zinc finger domains, a family of C2H2-type zinc fingers present in matrin, U1 small nuclear ribonucleoprotein C and other RNA-binding proteins. Matrin/U1-C-like, C2H2-type zinc finger ZMAT Zinc fingers matrin-type ZMAT NMTR Nuclear-encoded mitochondrial tRNAs nuclear-encoded mitochondrial-type tRNAs Nuclear-encoded mitochondrial transfer RNAs NMTR Cytoplasmic tRNAs TR Cytoplasmic transfer RNAs TR MT-T Mitochondrially encoded tRNAs Mitochondrially encoded transfer RNAs MT-T Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that primarily guide chemical modifications of other RNAs, mainly ribosomal RNAs, transfer RNAs and small nuclear RNAs. snoRNAs Small nucleolar RNAs C/D box snoRNAs contain two short conserved sequence motifs, C (RUGAUGA) and D (CUGA), located near the 5' and 3' ends of the snoRNA, respectively. Short regions (~ 5 nucleotides) located upstream of the C box and downstream of the D box are usually base complementary and form a stem-box structure, which brings the C and D box motifs into close proximity. This stem-box structure has been shown to be essential for correct snoRNA synthesis and nucleolar localization. C/D box snoRNAs SNORD fibrillarin-associated snoRNAs Small nucleolar RNAs, C/D box SNORD H/ACA box snoRNAs have a common secondary structure consisting of a two hairpins and two single-stranded regions termed a hairpin-hinge-hairpin-tail structure. H/ACA snoRNAs also contain conserved sequence motifs known as H box (consensus ANANNA) and the ACA box (ACA). Both motifs are usually located in the single-stranded regions of the secondary structure. GAR1‐associated snoRNAs H/ACA box snoRNAs SNORA Small nucleolar RNAs, H/ACA box SNORA Small Cajal body-specific RNAs (scaRNAs) are a class of small nucleolar RNAs (snoRNAs) that specifically localise to the Cajal body, a nuclear organelle involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs or snurps). ScaRNAs guide the modification ( methylation and pseudouridylation ) of RNA polymerase II transcribed spliceosomal RNAs U1, U2, U4, U5 and U12. The first scaRNA identified was U85. It is unlike typical snoRNAs in that it is a composite CACA box snoRNAs and can guide both pseudouridylation and 2'-O-methylation. Not all scaRNAs are composite C/D and H/ACA box snoRNA and most scaRNAs are structurally and functionally indistinguishable from snoRNAs, directing ribosomal RNA (rRNA) modification in the nucleolus. SCARNA scaRNAs Small Cajal body-specific RNAs SCARNA In molecular biology, ribosomal ribonucleic acid (rRNA) is the RNA component of the ribosome, and is essential for protein synthesis in all living organisms. It constitutes the predominant material within the ribosome, which is approximately 60% rRNA and 40% protein by weight. Ribosomes contain two major rRNAs and 50 or more proteins. The ribosomal RNAs form two subunits, the large subunit (LSU) and small subunit (SSU). The LSU rRNA acts as a ribozyme, catalyzing peptide bond formation. rRNA sequences are widely used for working out evolutionary relationships among organisms, since they are of ancient origin and are found in all known forms of life. rRNAs Ribosomal RNAs Small nuclear ribonucleic acid (snRNA), also commonly referred to as U-RNA, is a class of small RNA molecules that are found within the splicing speckles and cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribed by either RNA polymerase II or RNA polymerase III, and studies have shown that their primary function is in the processing of pre- messenger RNA ( hnRNA ) in the nucleus. They have also been shown to aid in the regulation of transcription factors (7SK RNA) or RNA polymerase II (B2 RNA), and maintaining the telomeres. U-RNAs U-sn RNAs snRNAs splicing snRNAs uridyl-rich small nuclear RNAs Small nuclear RNAs In molecular biology the MIZ-type zinc finger domain is a zinc finger-containing protein with homology to the yeast protein, Nfi-1. Miz1 is a sequence specific DNA binding protein that can function as a positive-acting transcription factor. Miz1 binds to the homeobox protein Msx2, enhancing the specific DNA-binding ability of Msx2. Other proteins containing this domain include the human pias family (protein inhibitor of activated STAT protein). The name MIZ is derived from M sx- i nteracting- z inc finger. The crystal structure of S. cerevisiae sumo e3 ligase siz1 containing this domain has been solved. MIZ zinc fingers SP-RING zinc fingers ZMIZ zf-MIZ Zinc fingers MIZ-type ZMIZ Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi proteins. These piRNA complexes have been linked to both epigenetic and post-transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, particularly those in spermatogenesis. They are distinct from microRNA (miRNA) in size (26-31 nt rather than 21-24 nt), lack of sequence conservation, and increased complexity. It remains unclear how piRNAs are generated, but potential methods have been suggested, and it is certain their biogenesis pathway is distinct from miRNA and siRNA, while rasiRNAs are a piRNA subspecies. PIRC piRNA clusters Piwi-interacting RNA clusters PIRC Many eukaryotic cells contain large ribonucleoprotein particles in the cytoplasm known as vaults. The vault complex comprises the major vault protein (MVP), two minor vault proteins (VPARP [PARP4] and TEP1), and a variety of small untranslated RNA molecules. Given the association with the nuclear membrane and the location within the cell, vaults are thought to play roles in intracellular and nucleocytoplasmic transport processes. Also, given that the structure and protein composition are highly conserved among species, it is believed that the roles vault plays are integral to eukaryotic function. VTRNA vault complex-associated RNAs vtRNAs Vault RNAs VTRNA Y RNAs are small non-coding RNAs. They are components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with systemic lupus erythematosus. RNAs, Ro-associated Y RNY Ro60 ribonucleoprotein particle RNAs Y RNAs RNAs, Ro60-associated Y RNY KCNT KNa channels Potassium channel, sodium activated subfamily T Slick/Slack family Slo2 family Sodium-activated potassium channels Potassium sodium-activated channel subfamily T KCNT BK channels [potassium large conductance calcium activated channels] have a tetrameric structure. Each monomer of the channel-forming alpha subunit is the product of the KCNMA1 gene. Modulatory beta subunits (encoded by KCNMB1, KCNMB2, KCNMB3, or KCNMB4) can associate with the tetrametic channel. BK channel beta subunits BK channel modulatory beta subunits Big potassium channel beta subunits KCNMB MaxiK channel regulatory subunits Potassium channel subfamily M regulatory beta subunits Slobeta subunits Potassium calcium-activated channel subfamily M regulatory beta subunits KCNMB Beta subunits are auxiliary proteins that associate with alpha subunits, sometimes in a alpha4beta4 stoichiometry. These subunits do not conduct current on their own but rather modulate the activity of Kv [potassium voltage gated ion] channels. Potassium channel, voltage gated regulatory beta subunits Potassium voltage-gated channel regulatory subunits MYM-type zinc fingers were identified in MYM family proteins. Human protein ZMYM3 is involved in a chromosomal translocation and may be responsible for X-linked retardation in XQ13.1. ZMYM2 is also involved in disease. In myeloproliferative disorders it is fused to FGF receptor 1; in atypical myeloproliferative disorders it is rearranged. Members of the family generally are involved in development. MYM-type Zinc fingers with FCS sequence motif TRASH domain containing ZMYM zf-FCS Zinc fingers MYM-type ZMYM BR-C, ttk and bab domain containing BTB (POZ) domain containing BTBD BTB domain containing BTBD Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a heme cofactor and, therefore, are hemoproteins. CYPs use a variety of small and large molecules as substrates in enzymatic reactions. They are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term P450 is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with CO. CYP enzymes have been identified in all domains of life - animals, plants, fungi, protists, bacteria, archaea, and even in viruses. However, the enzymes have not been found in E. coli. More than 21,000 distinct CYP proteins are known. CYP Cytochrome P450s CYP The EF hand is a helix-loop-helix structural domain or motif found in a large family of calcium-binding proteins. The EF-hand motif contains a helix-loop-helix topology, much like the spread thumb and forefinger of the human hand, in which the Ca 2+ ions are coordinated by ligands within the loop. The motif takes its name from traditional nomenclature used in describing the protein parvalbumin, which contains three such motifs and is probably involved in muscle relaxation via its calcium-binding activity. The EF-hand consists of two alpha helices linked by a short loop region (usually about 12 amino acids ) that usually binds calcium ions. EF hand domain containing EF-hand domain containing In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to 1 in human DNA). For example, each human cell has about 1.8 meters of DNA, (~6 ft) but wound on the histones it has about 90 micrometers (0.09�mm) of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes. Histones ANO Anoctamins ANO BEST Bestrophins BEST CLCA Calcium sensitive chloride conductance protein family Calcium-activated chloride channel regulator family Chloride channel accessory CLCA The glycine receptor, or GlyR, is the receptor for the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem. GLRA, GLRB Glycine receptors GLRA, GLRB In molecular biology the MYND-type zinc finger domain is a conserved protein domain. The MYND domain (myeloid, Nervy, and DEAF-1) is present in a large group of proteins that includes RP-8 (PDCD2), Nervy, and predicted proteins from Drosophila, mammals, Caenorhabditis elegans, yeast, and plants. The MYND domain consists of a cluster of cysteine and histidine residues, arranged with an invariant spacing to form a potential zinc-binding motif. Mutating conserved cysteine residues in the DEAF-1 MYND domain does not abolish DNA binding, which suggests that the MYND domain might be involved in protein-protein interactions. MYND zinc fingers ZMYND zf-MYND Zinc fingers MYND-type ZMYND Minor histocompatibility antigens (a.k.a. MHA) are receptors on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). Minor histocompatibility antigens are due to normal proteins that are in themselves polymorphic in a given population. Even when a transplant donor and recipient are identical with respect to their major histocompatibility complex genes, the amino acid differences in minor proteins can cause the grafted tissue to be slowly rejected. MHA MiHA mHAg mHags minor H antigen Minor histocompatibility antigens HOMER Homer scaffolding proteins Homer scaffold proteins HOMER The PHD finger was discovered in 1993 as a Cys 4 -His-Cys 3 motif in the plant homeodomain (hence PHD) proteins HAT3.1 in Arabidopsis thaliana and maize ZmHox1a. The PHD finger motif resembles the metal binding RING domain (Cys 3 -His-Cys 4 ) and FYVE domain. It occurs as a single finger, but often in clusters of two or three, and it also occurs together with other domains, such as the chromodomain and the bromodomain. PHD zinc fingers PHF Zinc fingers, PHD-type PHD finger proteins PHF IGH Immunoglobulin heavy IGH IGK Immunoglobulin kappa IGK IGL Immunoglobulin lambda IGL TRB T cell receptor beta TRB This group represents genes encoding proteins with the zinc finger domain found in RanBP2 proteins. Ran is an evolutionary conserved member of the Ras superfamily that regulates all receptor-mediated transport between the nucleus and the cytoplasm. Ran binding protein 2 (RanBP2) is a 358kDa nucleoporin located on the cytoplasmic side of the nuclear pore complex which plays a role in nuclear protein import . RanBP2 contains multiple zinc fingers which mediate binding to RanGDP. ZRANB zf-RanBP Zinc fingers RANBP2-type ZRANB In molecular biology a selenoprotein is any protein that includes a selenocysteine (Se-Cys) amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases (GPX) and three thioredoxin reductases, (TrxR/TXNRD) which both contain only one Se-Cys. Selenoprotein P is the most common selenoprotein found in the plasma. It is unusual because in humans it contains 10 Se-Cys residues, which are split into two domains, a longer N-terminal domain that contains 1 Se-Cys, and a shorter C-terminal domain that contains 9 Se-Cys. The longer N-terminal domain is likely an enzymatic domain, and the shorter C-terminal domain is likely a means of safely transporting the very reactive selenium atom throughout the body. SELENO Selenoprotein group Selenoproteins SELENO Matrix metalloproteinases (MMPs) are zinc -dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily. Collectively, these enzymes are capable of degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules. They are known to be involved in the cleavage of cell surface receptors, the release of apoptotic ligands (such as the FAS ligand ), and chemokine dispersion), differentiation, angiogenesis, apoptosis, and host defense. They were first described in vertebrates (1962), including humans, but have since been found in invertebrates and plants. They are distinguished from other endopeptidases by their dependence on metal ions as cofactors, their ability to degrade extracellular matrix, and their specific evolutionary DNA sequence. MMP MMPs matrix metalloproteinase matrixins M10 matrix metallopeptidases MMP The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors: TIMP1, TIMP2, TIMP3 and TIMP4. Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP- ) can form complexes with TIMPs when the enzymes are in the latent form. The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP ( MMP-14 ), a membrane-anchored MMP. The role of the pro-MMP-9/TIMP-1 complex is still unknown. TIMP TIMPs tissue inhibitor of metalloproteinases Tissue inhibitor of metallopeptidases TIMP In molecular biology, the astacins are a family of metallopeptidases. These metallopeptidases belong to the MEROPS peptidase family M12, subfamily M12A (astacin family, clan MA(M)). The protein fold of the peptidase domain for members of this family resembles that of thermolysin, the type example for clan MA, and the predicted active site residues for members of this family and thermolysin occur in the motif HEXXH. The astacin family of metalloendopeptidases (EC 3.4.24.21) encompasses a range of proteins found in hydra to humans, in mature and developmental systems. Their functions include activation of growth factors, degradation of polypeptides, and processing of extracellular proteins. The proteins are synthesised with N-terminal signal and pro-enzyme sequences, and many contain multiple domains C-terminal to the protease domain. They are either secreted from cells, or are associated with the plasma membrane. The astacin molecule adopts a kidney shape, with a deep active-site cleft between its N- and C-terminal domains. The zinc ion, which lies at the bottom of the cleft, exhibits a unique penta-coordinated mode of binding, involving 3 histidine residues, a tyrosine and a water molecule (which is also bound to the carboxylate side chain of Glu93). The N-terminal domain comprises 2 alpha-helices and a 5-stranded beta-sheet. The overall topology of this domain is shared by the archetypal zinc-endopeptidase thermolysin. Astacin protease domains also share common features with serralysins, matrix metalloendopeptidases, and snake venom proteases; they cleave peptide bonds in polypeptides such as insulin B chain and bradykinin, and in proteins such as casein and gelatin; and they have arylamidase activity. M12 metallopeptidases Astacins MAP kinase phosphatases Atypical dual specificity phosphatases M43B metallopeptidases PAPPA Pappalysins PAPPA There are three members of this family with broad specificity. They contain SH3-binding motifs as well as F-actin binding motifs, thus they are generally believed to play a role in the regulation of cytoskeletal rearrangements. In accordance with their proposed rule, proteins like ADF, cofilin and LIMK1 are slingshot substrates. SSH Slingshot protein phosphatases SSH PRLs PTP4A Phosphatases of Regenerating Liver Protein tyrosine phosphatases type IVA Protein tyrosine phosphatase 4A family PTP4A This entry represents the SWIM (SWI2/SNF2 and MuDR) zinc-binding domain, which is found in a variety of prokaryotic and eukaryotic proteins, such as mitogen-activated protein kinase kinase kinase 1 (or MEKK1). It is also found in the related protein MEX (MEKK1-related protein X), a testis-expressed protein that acts as an E3 ubiquitin ligase through the action of E2 ubiquitin-conjugating enzymes in the proteasome degradation pathway; the SWIM domain is critical for MEX ubiquitination. SWIM domains are also found in the homologous recombination protein Sws1, as well as in several hypothetical proteins. SWI2/SNF2 and MuDR zinc-binding domain containing SWIM zinc fringers ZSWIM Zinc fingers SWIM-type ZSWIM CDC14 phosphatases metzincin metalloproteases metzincin metalloproteinases metzincins Metzincin metallopeptidases PTEN protein phosphatases Myotubularin domain represents a region within eukaryotic myotubularin-related proteins that is sometimes found with the GRAM domain IPR004182. MTM Myotubularins MTM The membrane-associated guanylate kinases (MAGUK) are a superfamily of proteins. The MAGUKs are defined by their inclusion of PDZ, SH3 and GUK domains, although many of them also contain regions homologous of CaMKII, WW and L27 domains. The GUK domain that they have is structurally very similar to that of the guanylate kinases, however it is known to be catalytically inactive as the P-Loop which binds ATP is absent. It is thought that the MAGUKs have subfunctionalized the GUK domain for their own purposes, primarily based on its ability to form protein-protein interactions with cytoskeleton proteins, microtubule / actin based machinery and molecules involved in signal transduction. The PDZ domain which are contained in the MAGUKs in varying numbers. PDZ domains are short peptide binding sequences commonly found at the C-terminus of interacting proteins. Copies within each of the family members often have different binding partners, due to amino acid differences between the copies. The SH3 domain is again a protein-protein interaction domain. Its family generally bind to PXXP sites, but in MAGUKs it is known to bind to other sites as well. One of the most well known features is that it can form an intramolecular bond with the GUK domain, creating what is known as a GUK-SH3 'closed' state. MAGUKs Membrane associated guanylate kinases ANGPTL Angiopoietin like family ANGPTL CEACAM Carcinoembryonic antigen related cell adhesion molecule family CEA cell adhesion molecule family CEACAM CT antigen 21 family CTAGE Cutaneous T-cell-lymphoma-associated antigen family CTAGE family CTAGE Transferrins Cyclophilins are a family of proteins from vertebrates and other organisms that bind to cyclosporine, an immunosuppressant which is usually used to suppress rejection after internal organ transplants. These proteins have peptidyl prolyl isomerase activity, which catalyzes the isomerization of peptide bonds from trans form to cis form at proline residues and facilitates protein folding. Cyclophilin A is a cytosolic and highly abundant protein. The protein belongs to a family of isozymes, including cyclophilins B and C, and natural killer cell cyclophilin-related protein. Major isoforms have been found throughout the cell, including the ER, and some are even secreted. CYP PPI cyclophilins cyclosporin A (CsA) binding proteins Cyclophilin peptidylprolyl isomerases PPI In molecular biology the ZZ-type zinc finger domain is a type of protein domain that was named because of its ability to bind two z inc ions. These domains contain 4-6 Cys residues that participate in zinc binding (plus additional Ser/His residues), including a Cys-X2-Cys motif found in other zinc finger domains. These zinc fingers are thought to be involved in protein-protein interactions. The structure of the ZZ domain shows that it belongs to the family of cross-brace zinc finger motifs that include the PHD, RING, and FYVE domains. ZZZ Zinc fingers ZZ-type ZZZ FK506 binding proteins FKBP FKBP prolyl isomerase family FKBP ADGRA Adhesion G protein-coupled receptors, subfamily A ADGRA ADGRB BAI brain-specific angiogenesis inhibitors Adhesion G protein-coupled receptors, subfamily B ADGRB ADGRC CELSR Adhesion G protein-coupled receptors, subfamily C ADGRC ADGRD Adhesion G protein-coupled receptors, subfamily D ADGRD ADGRE EMR Adhesion G protein-coupled receptors, subfamily E ADGRE ADGRF Adhesion G protein-coupled receptors, subfamily F ADGRF ADGRG Adhesion G protein-coupled receptors, subfamily G ADGRG ADGRL LPHN latrophilins Adhesion G protein-coupled receptors, subfamily L ADGRL ADGRV Adhesion G protein-coupled receptors, subfamily V ADGRV PIN Parvulins PIN In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases that interconvert between the cis and trans positions. Immunophilins are targeted by immunosuppressive drugs such as Sirolimus (earlier rapamycin), cyclosporine, and tacrolimus. For these drugs in particular, known immunophilins such as cyclophilin catalyze the cis-trans isomerization of peptide bonds, particularly X-Pro peptide bonds. This isomerase activity can be inhibited by immunosuppressive drugs. Immunophilins Prolyl isomerase (also known as peptidylprolyl isomerase or PPIase ) is an enzyme ( EC 5.2.1.8 ) found in both prokaryotes and eukaryotes that interconverts the cis and trans isomers of peptide bonds with the amino acid proline. Proline has an unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its secondary amine nitrogen. Most amino acids have a strong energetic preference for the trans peptide bond conformation due to steric hindrance, but proline's unusual structure stabilizes the cis form so that both isomers are populated under biologically relevant conditions. Proteins with prolyl isomerase activity include cyclophilin, FKBPs, and parvulin, although larger proteins can also contain prolyl isomerase domains. EC 5.2.1.8 PPIs Peptidylproline cis-trans-isomerases Peptidylprolyl cis-trans isomerases Prolyl isomerases Peptidylprolyl isomerases Granin (chromogranin and secretogranin) is a protein family of regulated secretory proteins ubiquitously found in the cores of amine and peptide hormone and neurotransmitter dense-core secretory vesicles. SCG chemogranins secretogranins Granins SCG The rhomboid proteases are a family of enzymes that exist in almost all species. They are proteases : they cut the polypeptide chain of other proteins. This proteolytic cleavage is irreversible in cells, and an important type of cellular regulation. Although proteases are one of the earliest and best studied class of enzyme, rhomboids belong to a much more recently discovered type: the intramembrane proteases. What is unique about intramembrane proteases is that their active sites are buried in the lipid bilayer of cell membranes, and they cleave other transmembrane proteins within their transmembrane domains. About 30% of all proteins have transmembrane domains, and their regulated processing often has major biological consequences. Accordingly, rhomboids regulate many important cellular processes, and may be involved in a wide range of human diseases. RHB Rhomboid family RHB VPS9 domain containing Actins are globular multi-functional proteins that form microfilaments. An actin protein's mass is roughly 42- kDa and they are the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major components of the cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells. They can be present as either a free monomer called G-actin (globular) or as part of a linear polymer microfilament called F-actin (filamentous) both of which are essential for such important cellular functions as the mobility and contraction of cells during cell division. Actins participate in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape. Many of these processes are mediated by extensive and intimate interactions of actin with cellular membranes. In vertebrates, three main groups of actin isoforms, alpha, beta, and gamma have been identified. The alpha actins, found in muscle tissues, are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton, and as mediators of internal cell motility. ACT Actins ACT PAQR Progestin and adipoQ receptor family PAQR GINS GINS complex GINS COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is a protein complex with isopeptidase activity. It catalyses the hydrolysis of NEDD8 protein from the cullin subunit of Cullin-RING ubiquitin ligases (CRL). Therefore, it is responsible for CRL deneddylation - at the same time, it is able to bind denedyllated cullin-RING complex and retain them in deactivated form. COP9 signalosome thus serves as a sole deactivator of CRLs. It was found in all eukaryotic organisms including human; it was first discovered in plants. Human COP9 signalosome (total size ~350 kDa ) consists of 8 subunits - CSN1/COPS1, CSN2/COPS2, CSN3/COPS3, CSN4/COPS4, CSN5/COPS5, CSN6/COPS6, CSN7/COPS7A & COPS7B and CSN8/COPS8. All are essential for full function of the complex and mutation in some of them is lethal in mice. COPS CSN signalosome COP9 signalosome COPS The G protein-coupled bile acid receptor 1 (GPBAR1) also known G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or TGR5, is a protein that in humans is encoded by the GPBAR1 gene. GPBAR G protein-coupled bile acid receptor GPBAR Estrogen (G protein-coupled) receptor GPER G protein-coupled estrogen receptor GPER OXGR Oxoglutarate receptor OXGR SUCNR Succinate receptor SUCNR Histone deacetylases (EC 3.5.1.98, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an epsilon-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins. HDAC, SIRT Histone deacetylases KDAC KDACs Lysine deacetylases Histone deacetylase superfamily HDAC, SIRT Sirtuin or Sir2 proteins are a class of proteins that possess either mono-ADP-ribosyltransferase, or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity. Sirtuins regulate important biological pathways in bacteria, archaea and eukaryotes. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2 ', the gene responsible for cellular regulation in yeast. The term sirtuins is derived from the word 'sir-two-ins'. Sirtuins have been implicated in influencing a wide range of cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy efficiency and alertness during low-calorie situations. Sirtuins can also control circadian clocks and mitochondrial biogenesis. Yeast Sir2 and some, but not all, sirtuins are protein deacetylases. Unlike other known protein deacetylases, which simply hydrolyze acetyl - lysine residues, the sirtuin-mediated deacetylation reaction couples lysine deacetylation to NAD hydrolysis. This hydrolysis yields O-acetyl-ADP- ribose, the deacetylated substrate and nicotinamide, itself an inhibitor of sirtuin activity. The dependence of sirtuins on NAD links their enzymatic activity directly to the energy status of the cell via the cellular NAD:NADH ratio, the absolute levels of NAD, NADH or nicotinamide or a combination of these variables. Histone deacetylases, class III SIRT Sirtuins SIRT The plakins are a family of cytolinkers characterized by a multimodular structure that enables them to function as versatile cross-linkers of the cytoskeleton. They connect the microfilament, microtubule (MT), and intermediate filament (IF) systems with each other and with junctional complexes in organelle and plasma membranes, thereby contributing to cell shape and polarity. They also act as scaffolds and adaptors for signaling proteins that modulate cytoskeletal dynamics or cell migration, differentiation, and stress responses. Plakins The PARP-type zinc finger domains seem to bind specifically to single-stranded DNA and to act as a DNA nick sensor. DNA ligase III contains, in its N-terminal section, a single copy of a zinc finger highly similar to those of PARP. Zinc fingers PARP-type Hemoglobin; also spelled haemoglobin and abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates (with the exception of the fish family Channichthyidae ) as well as the tissues of some invertebrates. Hemoglobin in the blood carries oxygen from the respiratory organs (lungs or gills) to the rest of the body (i.e. the tissues). There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism. HB Haemoglobin subunits HgB Hemoglobin subunits HB Dynactin or Dynein activator complex is a multi-subunit protein found in eukaryotic cells that aids in bidirectional intracellular transport by binding to dynein and kinesin-2 and linking them to the organelle or vesicle to be transported. DCTN Dynein activator complex Dynactin subunits DCTN The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding. Selectins bind to sugar moieties and so are considered to be a type of lectin, cell adhesion proteins that bind sugar polymers. SEL Selectins SEL ENAH/VASPs are a family of closely related proteins involved in cell motility in vertebrate and invertebrate animals. ENAH/VASPs are modular proteins that are involved in actin polymerization, as well as interaction with other proteins. Within the cell, ENAH/VASP proteins are found at the leading edge of Lamellipodia and at the tips of filopodia. Ena, the founding member of the family was discovered in a Drosophila genetic screen for mutations that act as dominant suppressors of the abl non receptor tyrosine kinase. Invertebrate animals have one Ena homologue, whereas human and other mammals have three: ENAH, VASP and EVL. ENA-VASPs ENA/VASPs ENAH/VASPs ADAMTSL ADAMTS like ADAMTSL Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed in sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the latter 3 are not found in human. They received their name from their similarity to the protein coded by the toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard. The researchers were so surprised that they spontaneously shouted out in German, ' Das ist ja toll! ' which translates as 'That's great!' TLR Toll-like receptors Toll like receptors TLR Tektins are cytoskeletal proteins found in cilia and flagella as structural components of outer doublet microtubules. They are also present in centrioles and basal bodies. They are polymeric in nature, and form filaments. They include TEKT1, TEKT2, TEKT3, TEKT4, TEKT5. TEKT Tektins TEKT Gelsolin/villins 4.1 family Band 4.1 family EPB41 Erythrocyte membrane protein band 4.1 EPB41 SNAP(c) SNAPC small nuclear RNA activating complex subunits small nuclear RNA activating protein complex snRNA activating protein complex SNAP complex SNAPC Peroxiredoxins (Prxs, EC 1.11.1.15 ) are a ubiquitous family of antioxidant enzymes that also control cytokine -induced peroxide levels and thereby mediate signal transduction in mammalian cells. The physiological importance of peroxiredoxins is illustrated by their relative abundance (one of the most abundant proteins in erythrocytes after hemoglobin is peroxiredoxin 2). PRDX PRX family Prxs Peroxiredoxins PRDX Scramblase is a protein responsible for the translocation of phospholipids between the two monolayers of a lipid bilayer of a cell membrane. In humans, phospholipid scramblases (PLSCRs) constitute a family of five homologous proteins that are named as PLSCR1-PLSCR5. Scramblases are not members of the general family of transmembrane lipid transporters known as flippases. Scramblases are distinct from flippases and floppases. In fact, scramblases, flippases and floppases are three different types of enzymatic groups of phospholipid transportation enzymes. The inner-leaflet facing the inside of the cell contains negatively charged amino-phospholipids and phosphatidylethanolamine. The outer-leaflet, facing the outside environment, contains phosphatidylcholine and sphingomyelin. Scramblase is an enzyme, present in the cell membrane, that can transport (scramble ) the negatively charged phospholipids from the inner-leaflet to the outer-leaflet, and vice versa. PLSCR Phospholipid scramblases PLSCR X-linked Kx blood group related family XKR XK related family XKR Prefoldin is a family of proteins used in protein folding complexes. It is classified as a heterohexameric molecular chaperone in both archaea and eukarya, including humans. A prefoldin molecule works as a transfer protein in conjunction with a molecule of chaperonin to form a chaperone complex and correctly fold other nascent proteins. One of prefoldin's main uses in eukarya is the formation of molecules of actin for use in the eukaryotic cytoskeleton. PFDN Prefoldin subunits PFDN Peroxin (or peroxisomal/peroxisome biogenesis factor ) is a protein found in peroxisomes. Deficiencies are associated with several peroxisomal disorders. Numerous peroxin proteins serve several functions including the recognition of cytoplasmic proteins that contain peroxisomal targeting signals (PTS) that tag them for transport by peroxisomal proteins to the peroxisome. PEX peroxisomal biogenesis factors Peroxins PEX MS4 Membrane spanning 4-domains MS4 Caspase recruitment domains, or Caspase activation and recruitment domains ( CARDs ), are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs. CARD domains are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors. CARD Caspase recruitment domain containing CARD These genes encode proteins with a CW-type zinc finger motif, named for its conserved cysteine and tryptophan residues. It is predicted to be a highly specialised mononuclear four-cysteine (C4) zinc finger that plays a role in DNA binding and/or promoting protein-protein interactions in complicated eukaryotic processes including chromatin methylation status and early embryonic development. The domain is found exclusively in vertebrates, vertebrate-infecting parasites and higher plants. ZCW zf-CW Zinc fingers CW-type ZCW In molecular biology, ORC or origin recognition complex is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes. ORC is a central component for eukaryotic DNA replication, and binds chromatin at replication origins throughout the cell cycle. ORC directs DNA replication throughout the genome and is required for its initiation. ORC bound at replication origins serves as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (aka Cdt1), and the Mcm2 - Mcm7 complex. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase. Cell cycle -regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin -dependent protein kinase Cdc28 regulates initiation of DNA replication, including blocking reinitiation in G2 / M phase. In yeast, ORC also plays a role in the establishment of silencing at the mating-type loci Hidden MAT Left (HML) and Hidden MAT Right (HMR). ORC participates in the assembly of transcriptionally silent chromatin at HML and HMR by recruiting the Sir1 silencing protein to the HML and HMR silencers. Both Orc1 and Orc5 bind ATP, though only Orc1 has ATPase activity. The binding of ATP by Orc1 is required for ORC binding to DNA and is essential for cell viability. The ATPase activity of Orc1 is involved in formation of the pre-RC. ATP binding by Orc5 is crucial for the stability of ORC as a whole. Only the Orc1-5 subunits are required for origin binding; Orc6 is essential for maintenance of pre-RCs once formed. Interactions within ORC suggest that Orc2-3-6 may form a core complex. ORC Origin recognition complex ORC NDP Kinases NDPK NME awd NME/NM23 family NME The cystatins are a family of cysteine protease inhibitors which share a sequence homology and a common tertiary structure of an alpha helix lying on top of an anti-parallel beta strand. cysteine protease inhibitors cysteine proteinase inhibitors Cystatin superfamily CST Cystatins, type 2 CST CST Stefins Type I cystatins Cystatins, type 1 CST Kininogen Type III cystatins Cystatins, type 3 Fetuins Type IV cystatins Cystatins, type 4 Histatins are proteins found in saliva. They are antimicrobial and antifungal proteins, and have been found to play a role in wound-closure. A significant source of histatins is found in the serous fluid secreted by Ebner's glands, salivary glands at the back of the tongue. Here they offer some early defense against incoming microbes. The three major histatins are 1, 3, and 5. Histatin 2 is a degradation product of histatin 1, and all other histatins are degradation products of histatin 3. Therefore there are only two genes, HTN1 and HTN3. Histatins also precipitate tannins from solution - thus preventing alimentary adsorption. HTN Histatins and statherin HTN Proline-rich proteins (PRPs) is a class of intrinsically unstructured proteins (IUP) containing several repeats of a short proline-rich sequence. Many tannin -consuming animals secrete a tannin-binding protein ( mucin ) in their saliva. Tannin-binding capacity of salivary mucin is directly related to its proline content. Advantages in using salivary proline-rich proteins (PRPs) to inactivate tannins are: PRPs inactivate tannins to a greater extent than do dietary proteins; this results in reduced fecal nitrogen losses, PRPs contain non specific nitrogen and nonessential amino acids; this makes them more convenient for an animal to exploit rather than using up valuable dietary protein. An example of this class of protein is IB5, a human parotid salivary protein known to bind with polyphenols (binding responsible for the astringency mouth feel). PRB, PRH PRPs Proline rich salivary proteins Proline rich proteins PRB, PRH Proprotein convertases are a family of proteins that activate other proteins. Many proteins are inactive when they are first synthesized, because they contain chains of amino acids that block their activity. Proprotein convertases remove those chains and activate the protein. The prototypical proprotein convertase is furin. Proprotein convertases have medical significance, because they are involved in many important biological processes, such as cholesterol synthesis. Compounds called proprotein convertase inhibitors can block their action, and block the target proteins from becoming active. Many proprotein convertases, especially furin and PACE4, are involved in pathological processes such as viral infection, inflammation, hypercholesterolemia, and cancer, and have been postulated as therapeutic targets for some of these diseases. PCSK PCs Peptidase family S8 Proprotein convertases secretory proprotein convertases subtilisin/kexin-like proprotein convertases Proprotein convertase subtilisin/kexin family PCSK Acyl-CoA dehydrogenases (ACADs) are a class of enzymes that function to catalyze the initial step in each cycle of fatty acid β-oxidation in the mitochondria of cells. Their action results in the introduction of a trans double-bond between C2 (α) and C3 (β) of the acyl-CoA thioester substrate. Flavin adenine dinucleotide ( FAD ) is a required co-factor in addition to the presence of an active site glutamate in order for the enzyme to function. ACADs can be categorized into three distinct groups based on their specificity for short-, medium-, or long-chain fatty acid acyl-CoA substrates. While different dehydrogenases target fatty acids of varying chain length, all types of ACADs are mechanistically similar. Differences in the enzyme occur based on the location of the active site along the amino acid sequence. ACADs are an important class of enzymes in mammalian cells because of their role in metabolizing fatty acids present in ingested food materials. This enzyme's action represents the first step in fatty acid metabolism (the process of breaking long chains of fatty acids into acetyl CoA molecules). Deficiencies in these enzymes are linked to genetic disorders involving fatty acid oxidation (i.e. metabolic disorders). ACAD enzymes have been identified in animals (of which there are 9 major eukaryotic classes), as well as plants, nematodes, fungi, and bacteria. Five of these nine classes are involved in fatty acid β-oxidation (SCAD, MCAD, LCAD, VLCAD, and VLCAD2), and the other four are involved in branched chain amino acid metabolism (i3VD, i2VD, GD, and iBD). Most acyl-CoA dehydrogenases are α 4 homotetramers, and in two cases (for very long chain fatty acid substrates) they are α 2 homodimers. An additional class of acyl-CoA dehydrogenase was discovered that catalyzes α,β-unsaturation reactions with steroid-CoA thioesters in certain types of bacteria. This class of ACAD was demonstrated to form α 2 β 2 heterotetramers, rather than the usual α 4 homotetramer, a protein architecture that evolved in order to accommodate a much larger steroid-CoA substrate. ACADs are classified as EC 1.3.99.3. ACAD Acyl-CoA dehydrogenase family ACAD A calpain (EC 3.4.22.52, EC 3.4.22.53) is a protein belonging to the family of calcium -dependent, non- lysosomal cysteine proteases ( proteolytic enzymes ) expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the calpain proteases, the small regulatory subunit CAPNS1, also known as CAPN4, and the endogenous calpain-specific inhibitor, calpastatin. CANP CAPN CASF CDP Ca2+-activated neutral protease KAF intracellular Ca2+-dependent cysteine proteases Calpains CAPN CBX Chromobox family CBX CMTM CKLF like MARVEL transmembrane domain containing CMTM COMMD COMM domain containing COMMD DRC N-DRC nexin-dynein regulatory complex Dynein regulatory complex DRC E2F is a group of genes that codifies a family of transcription factors (TF) in higher eukaryotes. Three of them are activators: E2F1, 2 and E2F3a. Six others act as suppressors: E2F3b, E2F4-8. All of them are involved in the cell cycle regulation and synthesis of DNA in mammalian cells. E2Fs as TFs bind to the TTTCCCGC (or slight variations of this sequence) consensus binding site in the target promoter sequence. E2F E2F transcription factors E2F Desumoylases Peptidase family C48 SENP SUMO deconjugating proteases SUMO isopeptidases SUMO proteases SUMO specific proteases SUMO/Ulp family proteases Sentrin/SUMO specific proteases ULP family sentrin specific proteases SUMO specific peptidases SENP DESI Desumoylating isopeptidases DESI In molecular biology, transcription factor DP is a family of proteins which function as transcription factors. DP forms a heterodimer with E2F and regulates genes involved in cell cycle progression. The transcriptional activity of E2F is inhibited by the retinoblastoma protein which binds to the E2F-DP heterodimer [1] and negatively regulates the G1-S transition. TFDP dimerization partners of E2Fs Transcription factor Dp family TFDP USPL Ubiquitin specific peptidase like USPL HDAC Histone deacetylases, class I HDAC HDAC Histone deacetylases, class II HDAC HDAC Histone deacetylases, class IV HDAC HDAC Histone deacetylases, class IIA HDAC HDAC Histone deacetylases, class IIB HDAC A pyrin domain is a protein domain and a subclass of protein motif known as the death fold; it allows a pyrin domain containing protein to interact with other proteins that contain a pyrin domain. It is also known as a PYD or PAAD/DAPIN domain, and is distantly evolutionarily related to the Death domain family of protein domains.[1][2][3]Proteins containing a pyrin domain are frequently involved in biological processes called inflammation and apoptosis.[4][5] Proteins that possess a pyrin domain include intracellular microbial sensors called NOD-like receptors, and proteins associated with their function, such as PYCARD and certain fish caspases. DAPIN domain containing PAAD domain containing Pyrin domain containing PYHIN Pyrin and HIN domain family PYHIN DUB DUBs Deubiquitinases Deubiquinating enzymes josephin domain containing MJD deubiquinating enzymes UCH deubiquitinating enzymes UCH family UCHL Ubiquitin C-terminal hydrolases UCHL JAMM deubiquitinases JAMMs Jab1/Mov34/Mpr1 Pad1 N-terminal+ domain family M67 metallopeptidases JAMM/MPN+ metallopeptidase family is mentioned by