Melanoma, or malignant melanoma, is a highly aggressive cancer that develops in melanocytes. Many genes have been found to be mutated or amplified in melanoma, with the most commonly mutated genes being BRAF, CDKN2A, NRAS and TP53. MAPK and PI3K/Akt signaling are central to melanoma. This pathway is a summary of information from figures 1 and 2 from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520749/ Kunz and Vera] and supplemented with information from [https://www.kegg.jp/dbget-bin/www_bget?pathway+hsa05218 KEGG]. CDKN2A is frequently mutated in melanoma and germline mutations are associated with an increased susceptibility of developing skin cancer. The CDKN2A encodes two proteins, p16 (INK4A) and p14ARF, with different functions. p16 binds to CDK4, which prevents phosphorylation of Rb, thereby controlling the G1 to S transition. Without functioning p16, G1 to S transition can proceed. p14ARF is central to cell cycle regulation, inhibiting MDM2, which normally degrades p53, so loss of p14ARF has a similar effect to loss of p53. fab ca0 d7a b44 a2f b44 cb5 b44 b44 d64 afe e15 a2f Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18706 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18708 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18709 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:74769 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:18707 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:75669 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11651 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:23797 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:11652 SOS1; son of sevenless homolog 1 (Drosophila) Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:12015 Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:19211 CDK6; cyclin-dependent kinase 6 [EC:2.7.1.-] CDK4; cyclin-dependent kinase 4 [EC:2.7.1.-] CCND3; cyclin D3 E2F1; E2F transcription factor 1 E2F2; E2F transcription factor 2 E2F3; E2F transcription factor 3 V600E parentid=P04049; parentsymbol=RAF1; site=IGDFGLAtVksRWsG; position=thr491; sitegrpid=447748; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGTRSY; position=ser222; sitegrpid=448513; ptm=p; direction=u parentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyR; position=tyr187; sitegrpid=447594; ptm=p; direction=u parentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=u parentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyR; position=tyr204; sitegrpid=447543; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGTRSY; position=ser226; sitegrpid=448074; ptm=p; direction=u parentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=u parentid=P19419; parentsymbol=ELK1; site=RDLELPLsPsLLGGP; position=ser324; sitegrpid=471887; ptm=p; direction=u parentid=P19419; parentsymbol=ELK1; site=LsPIAPRsPAKLSFQ; position=ser389; sitegrpid=449757; ptm=p; direction=u parentid=Q92934; parentsymbol=BAD; site=EIRsRHssyPAGtED; position=ser75; sitegrpid=447860; ptm=p; direction=d parentid=P06400; position=ser249; ptm=p; direction=d parentid=P24385; position=thr286; ptm=p; direction=d 26091043 PubMed Genomic Classification of Cutaneous Melanoma. 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