identifier: traitmech:000648
label: unconventional protein secretion
definition: A physiological phenotype in which a eukaryotic microbial cell delivers
  protein cargo to the plasma membrane or extracellular space by a route that bypasses
  part or all of the conventional endoplasmic-reticulum-Golgi-plasma-membrane secretory
  itinerary.
definition_source: DOI:10.3389/fcell.2022.852028
trait_category: PHYSIOLOGY
term_kind: CLASS
mapping_status: PROPOSED
parent_traits:
- METPO:1000059
evidence:
- reference: DOI:10.3389/fcell.2022.852028
  snippet: Our results show that neosynthesized PmaA and PalI are translocated to
    the PM via Golgi-bypass, similar to nutrient transporters.
  notes: PMID:35465316, PMC9021693. Scientific Abstract and selected Introduction,
    Results and Methods directly read in Europe PMC XML. The paper includes membrane-cargo
    delivery within unconventional protein secretion. Aspergillus nidulans fluorescent
    cargo, conditional trafficking repression and localization assays support Golgi
    bypass after COPII-dependent ER exit, not soluble extracellular release or universal
    ER independence. The reporters and promoter replacements are engineered; no natural
    canonical exemplar is inferred. Actual panels, supplements and independent recipient-strain
    provenance were not inspected.
- reference: DOI:10.7554/eLife.16299
  snippet: Under these conditions Acb1, but not Cof1, was detected in the cell wall
    extract of starving cells
  notes: PMID:27115345, PMC4868542. Contiguous full-text Results s2-1 span, directly
    read in Europe PMC XML, not an abstract quote. Mild extraction detects intact
    Acb1 outside the plasma membrane of starved Saccharomyces cerevisiae with Cof1
    leakage and Bgl2 extraction controls. This is cell-wall/periplasmic recovery,
    not direct detection in culture medium. Harsh extraction, some mutants, heat and
    DMSO can invalidate the assay through leakage. The direct assay differs from earlier
    SDF-2 bioactivity assays and does not support a Vps4 requirement. Static CUPS
    images do not prove a temporal sequence. Actual panels and strain provenance remain
    uninspected.
- reference: DOI:10.1083/jcb.201407119
  snippet: Altogether our findings indicate that CUPS are not specialized autophagosomes
    as suggested previously.
  notes: PMID:25512390, PMC4274258. Scientific Abstract abstract2, distinct from the
    precis, and Introduction directly read in Europe PMC XML. The authors revise the
    earlier autophagosome interpretation of yeast CUPS. This is compartment-identity
    boundary evidence, not proof that every unconventional route excludes all autophagy-related
    machinery. Actual panels, full Methods and strain provenance were not inspected.
- reference: DOI:10.1083/jcb.202312120
  snippet: Notably, while CUPS remain stable, the modified TGN undergoes remodeling
    during the later stages of unconventional secretion.
  notes: PMID:40015244, PMC11867701. Scientific Abstract, not the teaser, and selected
    Results, Discussion and Methods directly read in Europe PMC XML. Yeast CUPS contact
    a modified trans-Golgi network; this argues against defining the phenotype by
    absence of all Golgi-derived membranes. Rcy1 and v-SNARE perturbations reduce
    cell-wall recovery of Acb1, SOD1 and Trx2 with Cof1 controls. Drs2-deleted cells
    could not be assayed because of lysis concerns. Cargo collection and final delivery
    through the proposed CUPS-TGN route remain a model. BY4741 derivatives include
    engineered reporters and mutants. Actual panels and supplements were not visually
    inspected.
discussions:
- discussion_id: unconventional-secretion-scope-and-mapping
  prompt: Keep cargo destinations and route-specific meanings distinct.
  kind: CURATION_TODO
  status: OPEN
  rationale: The broad usage in DOI:10.3389/fcell.2022.852028 includes plasma-membrane
    delivery after ER entry; DOI:10.7554/eLife.16299 describes an ER-bypassing soluble-cargo
    route. Preserve both, rather than treating leaderless secretion, Golgi bypass
    or secretory autophagy as exact synonyms. This concerns traffic performed by a
    eukaryotic microbe, not its animal or plant host. An absent predicted signal peptide,
    ATG dependence, CUPS formation or protein detected after lysis alone is insufficient.
    Membrane localization does not establish soluble release. The degradative autophagy
    record traitmech:000638 is not a broader parent; exocytosis traitmech:000637 specifies
    fusion-pore release rather than an unconventional itinerary. Overlap is not disjointness.
    Obsolete METPO secretion classes do not supply an active exact term. Keep METPO:1000059
    as parent and leave ontology equivalences and finer route hierarchy for human
    review.
  posed_by: codex
  posed_date: '2026-10-06'
- discussion_id: unconventional-secretion-exemplars-and-mechanisms
  prompt: Resolve natural exemplars and mechanisms separately for each route.
  kind: KNOWLEDGE_GAP
  status: OPEN
  rationale: Retain qualified laboratory observations without labeling engineered
    fluorescent cargo or conditional trafficking mutants as natural canonical exemplars.
    Natural strain provenance, source figures and accession-level functional evidence
    need further review before adding examples or a protein-resolved graph. The three
    CUPS papers share investigators and are not independent-laboratory replications;
    the Aspergillus study supports a different route, not replication of CUPS. No
    universal starvation trigger, signal-peptide absence, COPII independence, autophagosome
    or conserved export apparatus is asserted. ATG-dependent export remains a possible
    narrower research target, not an allocated additional trait.
  posed_by: codex
  posed_date: '2026-10-06'
curation_history:
- timestamp: '2026-10-06T18:32:51Z'
  curator: codex
  action: MINTED_TRAITMECH_ID
  changes: Added unconventional protein secretion with four DOI-backed snippets and
    explicit soluble-export, membrane-delivery, route and assay limits. Ignored-and-hidden
    searches and pinned METPO review found no exact record. Reserved METPO:1060100
    in v524. Deferred unverified mappings, natural exemplars and protein mechanisms;
    existing records remain unchanged.
  llm_assisted: true
- timestamp: '2026-10-06T18:43:11Z'
  curator: codex
  action: CURATED_WITH_LITERATURE
  changes: Clarified the conventional itinerary through plasma-membrane delivery (#1760),
    preserving the definition source's inclusion of unconventional post-Golgi export.
    No new route, cargo, taxon or universal mechanism is inferred.
  llm_assisted: true