TRAPPC8

UniProt ID: Q9Y2L5
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TRAPPC8 is the mammalian Trs85 ortholog and a TRAPPIII-associated TRAPP subunit. It contributes to TRAPPIII/RAB1 trafficking, ER-to-Golgi transport, ATG9 cycling required for autophagy initiation, and collagen-cargo secretion through TMEM131/TRAPP III context. Autophagophore recruitment is directly supported for TRAPPC8 by mammalian TBC1D14/TRAPPIII/ATG9 evidence.

Existing Annotations Review

GO Term Evidence Action Reason
GO:1990072 TRAPPIII protein complex
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC8 is a TRAPPIII-associated Trs85 ortholog.
Reason: Accept as core complex membership. TRAPPC8 is the mammalian Trs85 ortholog and is directly implicated in mammalian TRAPPIII-like/autophagy and secretory trafficking complexes.
Supporting Evidence:
PMID:21525244
KIAA1012 was annotated in GenBank as TRAPPC8, a Trs85p orthologue
PMID:26711178
TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
PMID:27066478
TRAPP III, which contains core TRAPP plus TrappC8, 11-13
Reactome:R-HSA-8877475
RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) and contribute to the localization of ATG9
GO:0005794 Golgi apparatus
IEA
GO_REF:0000044 		ACCEPT
Summary: Golgi apparatus localization is consistent with TRAPPC8/TRAPPIII trafficking biology.
Reason: Accept as a supported location/context for TRAPPC8-containing TRAPP reactions.
Supporting Evidence:
PMID:21525244
C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking
PMID:26711178
TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0005515 protein binding
IPI
PMID:21453443
Organization and assembly of the TRAPPII complex. 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC8 function.
Reason: Mark as over-annotated. Specific TRAPPC8 interactions are better represented as TRAPP/TRAPPIII complex membership, TBC1D14/TRAPPIII autophagy context, or TMEM131-dependent collagen cargo transport.
Supporting Evidence:
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:26711178
is required for TBC1D14 to bind TRAPPIII
PMID:32095531
mCherry-tagged TMEM131 Ct specifically pulled down the GFP-tagged TRAPPC8 fragment
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC8 function.
Reason: Mark as over-annotated. Specific TRAPPC8 interactions are better represented as TRAPP/TRAPPIII complex membership, TBC1D14/TRAPPIII autophagy context, or TMEM131-dependent collagen cargo transport.
Supporting Evidence:
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:26711178
is required for TBC1D14 to bind TRAPPIII
PMID:32095531
mCherry-tagged TMEM131 Ct specifically pulled down the GFP-tagged TRAPPC8 fragment
GO:0005737 cytoplasm
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: cytoplasm localization is consistent with TRAPPC8/TRAPPIII trafficking biology.
Reason: Accept as a supported location/context for TRAPPC8-containing TRAPP reactions.
Supporting Evidence:
PMID:21525244
C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking
PMID:26711178
TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC8 participates in ER-to-Golgi trafficking through TRAPP/TRAPPIII.
Reason: Accept as a core process. TRAPPC8 depletion affects Golgi/secretory traffic and TRAPPC8-containing TRAPP III transports collagen cargo from ER to Golgi.
Supporting Evidence:
PMID:21525244
C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking
PMID:26711178
TRAPPC8 modulates autophagy and secretory trafficking
PMID:32095531
TRAPPC8-containing TRAPP III is critical for the ER-to-Golgi transport of collagen cargos
GO:0048208 COPII vesicle coat assembly
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		MODIFY
Summary: The COPII annotation captures cargo transport context but overstates TRAPPC8 as a coat-assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC8/TRAPP III promotes ER-to-Golgi transport of collagen cargo in COPII context, but the evidence does not show TRAPPC8 assembling the COPII coat.
Supporting Evidence:
PMID:32095531
TRAPPC8-containing TRAPP III is critical for the ER-to-Golgi transport of collagen cargos
PMID:32095531
C-terminal recruitment of TRAPP III for the ER-to-Golgi transport of collagen cargo
Reactome:R-HSA-8877475
TRAPPCII is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein SEC23
GO:0099022 obsolete vesicle tethering
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		MODIFY
Summary: The obsolete vesicle-tethering annotation should not be retained as-is.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC8/TRAPP process. Mammalian TRAPP tethering remains unresolved and this term is obsolete.
Supporting Evidence:
PMID:27066478
evidence that any TRAPP complex acts as a membrane tether is currently inconclusive
PMID:21525244
C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking
PMID:32095531
TRAPPC8-containing TRAPP III is critical for the ER-to-Golgi transport of collagen cargos
GO:1990072 TRAPPIII protein complex
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC8 is a TRAPPIII-associated Trs85 ortholog.
Reason: Accept as core complex membership. TRAPPC8 is the mammalian Trs85 ortholog and is directly implicated in mammalian TRAPPIII-like/autophagy and secretory trafficking complexes.
Supporting Evidence:
PMID:21525244
KIAA1012 was annotated in GenBank as TRAPPC8, a Trs85p orthologue
PMID:26711178
TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
PMID:27066478
TRAPP III, which contains core TRAPP plus TrappC8, 11-13
Reactome:R-HSA-8877475
RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) and contribute to the localization of ATG9
GO:0032964 collagen biosynthetic process
IMP
PMID:32095531
Broadly conserved roles of TMEM131 family proteins in intrac... 		MODIFY
Summary: TRAPPC8 supports collagen cargo transport, but collagen biosynthesis is too broad and mechanistically imprecise.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. The paper supports TRAPPC8-dependent collagen cargo trafficking via TMEM131/TRAPP III, not direct collagen biosynthetic chemistry.
Supporting Evidence:
PMID:32095531
TRAPPC8-containing TRAPP III is critical for the ER-to-Golgi transport of collagen cargos
PMID:32095531
C-terminal recruitment of TRAPP III for the ER-to-Golgi transport of collagen cargo
PMID:32095531
RNAi-mediated depletion of expression of trpp-8, the C. elegans homolog of TRAPPC8, strongly reduced the abundance of COL-19::GFP
GO:0007030 Golgi organization
IMP
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		KEEP AS NON CORE
Summary: Golgi organization is a direct TRAPPC8-depletion phenotype but is secondary to early secretory trafficking.
Reason: Keep as non-core. Golgi fragmentation is a useful readout of TRAPPC8/TRAPP early secretory pathway disruption, while the core process is ER-to-Golgi/TRAPPIII trafficking.
Supporting Evidence:
PMID:21525244
C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking
GO:0005515 protein binding
IPI
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC8 function.
Reason: Mark as over-annotated. Specific TRAPPC8 interactions are better represented as TRAPP/TRAPPIII complex membership, TBC1D14/TRAPPIII autophagy context, or TMEM131-dependent collagen cargo transport.
Supporting Evidence:
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:26711178
is required for TBC1D14 to bind TRAPPIII
PMID:32095531
mCherry-tagged TMEM131 Ct specifically pulled down the GFP-tagged TRAPPC8 fragment
GO:0030008 TRAPP complex
IDA
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		ACCEPT
Summary: TRAPPC8 is a bona fide mammalian TRAPP subunit.
Reason: Accept as TRAPP complex membership. TRAPPC8/KIAA1012 copurifies with TRAPP components and is part of mammalian TRAPPIII-like biology.
Supporting Evidence:
PMID:21525244
C8 (KIAA1012) was found to copurify with TAP-C3
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:26711178
TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
GO:0005829 cytosol
TAS
Reactome:R-HSA-8877475 		ACCEPT
Summary: cytosol localization is consistent with TRAPPC8/TRAPPIII trafficking biology.
Reason: Accept as a supported location/context for TRAPPC8-containing TRAPP reactions.
Supporting Evidence:
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
PMID:26711178
TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
GO:0006914 autophagy
IMP
PMID:26711178
TBC1D14 regulates autophagy via the TRAPP complex and ATG9 t... 		NEW
Summary: TRAPPC8-containing mammalian TRAPPIII regulates bulk macroautophagy through ATG9 trafficking.
Reason: Add as a new direct process annotation. TRAPPC8 is specifically shown to modulate autophagy and maintain ATG9 cycling needed for autophagy initiation.
Supporting Evidence:
PMID:26711178
TRAPPC8 modulates autophagy and secretory trafficking
PMID:26711178
maintaining the cycling pool of ATG9 required for initiation of autophagy
PMID:26711178
Our findings are the first to clearly characterise a role for mammalian TRAPP, in particular TRAPPC8, in bulk macroautophagy

Core Functions

TRAPPC8 contributes the Trs85-like TRAPPIII subunit to TRAPP/RAB1 trafficking. This supports ER-to-Golgi transport, ATG9 cycling needed for autophagy initiation, and collagen-cargo trafficking in TMEM131/TRAPP III contexts. It should be modeled as contributing to TRAPPIII/TRAPP complex activity rather than independently enabling GEF activity.

Directly Involved In:
endoplasmic reticulum to Golgi vesicle-mediated transport autophagy
Cellular Locations:
cytosol cytoplasm Golgi apparatus
In Complex:
TRAPPIII protein complex
Supporting Evidence:
  • PMID:26711178
    TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex
  • PMID:26711178
    TRAPPC8 modulates autophagy and secretory trafficking
  • PMID:26711178
    maintaining the cycling pool of ATG9 required for initiation of autophagy
  • PMID:26711178
    Our findings are the first to clearly characterise a role for mammalian TRAPP, in particular TRAPPC8, in bulk macroautophagy
  • PMID:21525244
    C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking
  • PMID:32095531
    TRAPPC8-containing TRAPP III is critical for the ER-to-Golgi transport of collagen cargos
  • Reactome:R-HSA-8877475
    RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
  • Reactome:R-HSA-8877475
    RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) and contribute to the localization of ATG9

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
PMID:21453443
Organization and assembly of the TRAPPII complex.
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
PMID:32095531
Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Reactome:R-HSA-8877475
TRAPPC complexes exchange GTP for GDP on RAB1
PMID:26711178
TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic.

Suggested Questions for Experts

Q: Should TRAPPC8 receive a direct autophagy or ATG9 trafficking annotation in GOA based on PMID:26711178?

Suggested experts: GO autophagy editors, Sharon A. Tooze

Q: Should the collagen biosynthetic process annotation for TRAPPC8 be replaced by ER-to-Golgi vesicle-mediated transport with collagen-cargo context?

Suggested experts: GO extracellular matrix editors, GO transport editors

Q: Should TRAPPC8 be curated primarily as a TRAPPIII-specific subunit rather than a generic TRAPP-complex component in human?

Suggested experts: ComplexPortal curators, Reactome TRAPP curators

Suggested Experiments

Experiment: Deplete or rescue TRAPPC8 in mammalian cells and quantify ATG9 cycling, omegasome formation, LC3/WIPI2 puncta, and RAB1 activation.

Hypothesis: TRAPPC8-containing TRAPPIII promotes autophagy initiation by maintaining ATG9 cycling through RAB1-dependent trafficking.

Type: autophagy trafficking rescue assay

Experiment: Reconstitute TRAPPC8-containing TRAPPIII with and without TBC1D14 or TMEM131 fragments and measure RAB1 exchange plus cargo membrane recruitment.

Hypothesis: TRAPPC8 enables adaptor/cargo-specific recruitment of TRAPPIII while contributing to complex-level RAB1 GEF activity.

Type: complex reconstitution and RAB1 GEF assay

Experiment: Compare collagen secretion, VSVG ER-Golgi transport, and autophagy initiation in TRAPPC8 mutant/rescue cells to separate cargo-specific and general trafficking roles.

Hypothesis: TRAPPC8 supports both general TRAPPIII ER-Golgi traffic and specialized collagen/ATG9 cargo routes.

Type: parallel cargo-trafficking assay

📚 Additional Documentation

Notes

(TRAPPC8-notes.md)

TRAPPC8 notes

Review started from just fetch-gene human TRAPPC8. The proteostasis network places TRAPPC8 under Autophagy-Lysosome Pathway > Autophagophore initiation and elongation > Autophagy component recruitment to autophagophore > TRAPP complex component.

Falcon deep research was requested with just deep-research-falcon human TRAPPC8, but the provider timed out after 600 seconds and did not produce TRAPPC8-deep-research-falcon.md. The review therefore relies on the cached UniProt, GOA, Reactome, publication, and PN context files listed here.

TRAPPC8 is the mammalian Trs85 ortholog and a TRAPPIII-associated TRAPP subunit. The mammalian TRAPP component paper identifies KIAA1012/TRAPPC8 as a Trs85p ortholog and says "KIAA1012 was annotated in GenBank as TRAPPC8, a Trs85p orthologue" PMID:21525244. The TRAPP review lists TrappC8 as a TRAPP III-specific Trs85 ortholog and states that mammalian TRAPP III contains core TRAPP plus TrappC8, 11-13 PMID:27066478. Accept TRAPPIII and TRAPP complex membership.

TRAPPC8 has direct mammalian autophagy evidence, unlike several shared small core subunits. The TBC1D14 paper states that "TRAPPC8, the mammalian orthologue of a yeast autophagy-specific TRAPP subunit, forms part of a mammalian TRAPPIII-like complex" and that "TRAPPC8 modulates autophagy and secretory trafficking" PMID:26711178. It further concludes that TBC1D14/TRAPPIII maintain "the cycling pool of ATG9 required for initiation of autophagy" PMID:26711178. This supports including autophagy/ATG9 trafficking in the core function synthesis, even though the current seeded GOA lacks a direct autophagy process row.

TRAPPC8 also has ER-to-Golgi and collagen-cargo transport evidence. PMID:21525244 reports that C8 depletion causes Golgi fragmentation and supports an early secretory pathway role; it says C8 is a bona fide TRAPP subunit and that "C8 depletion causes Golgi fragmentation, supporting a role for the mammalian orthologue in ER-to-Golgi trafficking" PMID:21525244. The TMEM131 paper says "TRAPPC8-containing TRAPP III is critical for the ER-to-Golgi transport of collagen cargos" and that TMEM131 recruits TRAPP III "for the ER-to-Golgi transport of collagen cargo" PMID:32095531. Therefore, accept ER-to-Golgi transport, but modify collagen biosynthetic process to ER-to-Golgi vesicle-mediated transport because TRAPPC8 acts in collagen cargo trafficking rather than collagen biosynthesis chemistry.

The Golgi organization row is direct but should be non-core. C8 depletion produces Golgi fragmentation in the mammalian TRAPP paper, but this is best interpreted as a consequence/readout of early secretory pathway disruption rather than the core function itself. Keep as non-core.

The COPII coat assembly and obsolete vesicle tethering annotations are over-specific. The collagen paper places TRAPPC8/TRAPP III in ER-to-Golgi transport of collagen cargo in COPII vesicles, but it does not show TRAPPC8 assembling the COPII coat. The TRAPP review says "evidence that any TRAPP complex acts as a membrane tether is currently inconclusive" PMID:27066478. Modify these annotations to ER-to-Golgi vesicle-mediated transport.

Generic protein binding annotations should be marked as over-annotated. The interaction evidence is specific to TRAPP architecture, TBC1D14/TRAPP, or TMEM131/TRAPPC8, and should not be represented as generic protein binding.

Annotation stance:
- Core: TRAPPIII/TRAPP complex membership, contributes-to TRAPP/TRAPPIII RAB1 GEF activity, ER-to-Golgi vesicle-mediated transport, ATG9/autophagy trafficking context, Golgi/cytosol/cytoplasm.
- Non-core: Golgi organization as a depletion phenotype/readout.
- Modify: collagen biosynthetic process, COPII vesicle coat assembly, and obsolete vesicle tethering to ER-to-Golgi vesicle-mediated transport.
- Mark over-annotated: generic protein binding rows.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: the prior wording described autophagophore recruitment as PN-specific and directly supported for TRAPPC8 by mammalian TBC1D14/TRAPPIII/ATG9 evidence.

Pn Notes

(TRAPPC8-pn-notes.md)

TRAPPC8 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y2L5
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: TRAPPC8 is the mammalian Trs85 ortholog and a TRAPPIII-associated TRAPP subunit. It contributes to TRAPPIII/RAB1 trafficking, ER-to-Golgi transport, ATG9 cycling required for autophagy initiation, and collagen-cargo secretion through TMEM131/TRAPP III context. Autophagophore recruitment is directly supported for TRAPPC8 by mammalian TBC1D14/TRAPPIII/ATG9 evidence.
  • Existing/core annotation action counts: ACCEPT: 7; KEEP_AS_NON_CORE: 1; MARK_AS_OVER_ANNOTATED: 3; MODIFY: 3; NEW: 1

PN Consistency Summary

  • Consistency: Coherent and the strongest autophagy case. Notes, review, PN row ("TRAPP III, specific subunit"), and node mapping agree TRAPPC8 (Trs85 ortholog) is the TRAPPIII-specific subunit driving ATG9 cycling for autophagy initiation. Review adds GO:0006914 autophagy as action: NEW (IMP, PMID:26711178), modifies collagen biosynthetic process (GO:0032964) and COPII coat assembly to ER-to-Golgi transport, keeps Golgi organization non-core. No contradictions.
  • PN story / NEW pressure: PN asserts ATG9/ATG2 trafficking + TRAPPIII autophagy — and unlike the core subunits this is directly supported for TRAPPC8 (PMID:26711178 "maintaining the cycling pool of ATG9 required for initiation of autophagy"; "first to clearly characterise a role for mammalian TRAPP, in particular TRAPPC8, in bulk macroautophagy"). The review's NEW GO:0006914 autophagy is fully defensible. Conclusion: ADD (already proposed as NEW in the review).
  • Evidence alignment: Best overlap of the set: PN row uniquely lists PMID:26711178 (TBC1D14/TRAPP/ATG9), which the review uses as the load-bearing NEW-autophagy citation. Plus PMID:21525244, PMID:32095531 (TMEM131/collagen), PMID:27066478. No miscitation.
  • Verdict: Consistent; ACCEPT mapping + endorse NEW autophagy (GO:0006914). Strongest PN-story-to-evidence match in the TRAPP set.

Full Consistency Review

  • UniProt: Q9Y2L5 · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component ; PN-node mapping: type-leaf mapped, scope=ok_for_propagation_to_go, GO:0030008 TRAPP complex (already_in_goa_exact)
  • Consistency: Coherent and the strongest autophagy case. Notes, review, PN row ("TRAPP III, specific subunit"), and node mapping agree TRAPPC8 (Trs85 ortholog) is the TRAPPIII-specific subunit driving ATG9 cycling for autophagy initiation. Review adds GO:0006914 autophagy as action: NEW (IMP, PMID:26711178), modifies collagen biosynthetic process (GO:0032964) and COPII coat assembly to ER-to-Golgi transport, keeps Golgi organization non-core. No contradictions.
  • PN story / NEW pressure: PN asserts ATG9/ATG2 trafficking + TRAPPIII autophagy — and unlike the core subunits this is directly supported for TRAPPC8 (PMID:26711178 "maintaining the cycling pool of ATG9 required for initiation of autophagy"; "first to clearly characterise a role for mammalian TRAPP, in particular TRAPPC8, in bulk macroautophagy"). The review's NEW GO:0006914 autophagy is fully defensible. Conclusion: ADD (already proposed as NEW in the review).
  • Mapping strategy: No change to node. Projected GO:0030008 (OLS-verified) already in GOA; review also carries TRAPPIII (GO:1990072, whose OLS definition notes autophagy regulation). The PN component-bucket scope is narrower than the gene's NEW autophagy annotation — correctly leaving autophagy at the gene level rather than projecting it from the bucket.
  • Evidence alignment: Best overlap of the set: PN row uniquely lists PMID:26711178 (TBC1D14/TRAPP/ATG9), which the review uses as the load-bearing NEW-autophagy citation. Plus PMID:21525244, PMID:32095531 (TMEM131/collagen), PMID:27066478. No miscitation.
  • Verdict: Consistent; ACCEPT mapping + endorse NEW autophagy (GO:0006914). Strongest PN-story-to-evidence match in the TRAPP set.
  • Recommended edits: Optionally make the NEW term more specific to the autophagophore-recruitment leaf (e.g. GO:0000045 autophagosome assembly, OLS-verified) if ATG9-cycling/initiation evidence is judged to support assembly rather than only broad autophagy; otherwise GO:0006914 stands.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/TRAPPC8/TRAPPC8-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Autophagy component recruitment to autophagophore | TRAPP complex component

  • UniProt: Q9Y2L5
  • In branches: ALP
  • Notes: TRAPP III complex, specific subunit. The TRAPP complex serves as a GEF for RAB1. Involved in ATG9 and ATG2 trafficking
  • PN references (titles):
    • Membrane Trafficking in Autophagy - ScienceDirect
    • Frontiers | TRAPP Complexes in Secretion and Autophagy | Cell and Developmental Biology (frontiersin.org)
    • TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic | The EMBO Journal (embopress.org)
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0030008 TRAPP complex]
      rationale: This PN leaf is a curated component bucket for TRAPP subunits used in autophagophore recruitment. The matching GO cellular-component term is TRAPP complex, and the member genes already converge strongly on that assignment in existing GOA.
    • [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0030008 TRAPP complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q9Y2L5
gene_symbol: TRAPPC8
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TRAPPC8 is the mammalian Trs85 ortholog and a TRAPPIII-associated TRAPP subunit. It contributes to
  TRAPPIII/RAB1 trafficking, ER-to-Golgi transport, ATG9 cycling required for autophagy initiation,
  and collagen-cargo secretion through TMEM131/TRAPP III context. Autophagophore recruitment is
  directly supported for TRAPPC8 by mammalian TBC1D14/TRAPPIII/ATG9 evidence.
alternative_products:
- name: '1'
  id: Q9Y2L5-1
- name: '2'
  id: Q9Y2L5-2
  sequence_note: VSP_014454, VSP_004000
existing_annotations:
- term:
    id: GO:1990072
    label: TRAPPIII protein complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: TRAPPC8 is a TRAPPIII-associated Trs85 ortholog.
    action: ACCEPT
    reason: Accept as core complex membership. TRAPPC8 is the mammalian Trs85
      ortholog and is directly implicated in mammalian TRAPPIII-like/autophagy
      and secretory trafficking complexes.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - &id009
      reference_id: PMID:21525244
      supporting_text: KIAA1012 was annotated in GenBank as TRAPPC8, a Trs85p
        orthologue
    - &id001
      reference_id: PMID:26711178
      supporting_text: TRAPPC8, the mammalian orthologue of a yeast
        autophagy-specific TRAPP subunit, forms part of a mammalian
        TRAPPIII-like complex
    - &id010
      reference_id: PMID:27066478
      supporting_text: TRAPP III, which contains core TRAPP plus TrappC8, 11-13
    - &id011
      reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 and the TRAPPCIII complex play a role in the
        formation of the pre-autophagosomal structure (PAS) and contribute to
        the localization of ATG9
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Golgi apparatus localization is consistent with TRAPPC8/TRAPPIII
      trafficking biology.
    action: ACCEPT
    reason: Accept as a supported location/context for TRAPPC8-containing TRAPP
      reactions.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - Reactome:R-HSA-8877475
    supported_by:
    - &id005
      reference_id: PMID:21525244
      supporting_text: C8 depletion causes Golgi fragmentation, supporting a
        role for the mammalian orthologue in ER-to-Golgi trafficking
    - *id001
    - &id006
      reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 nucleotide exchange is stimulated in these pathways
        by the GEF activity of the multisubunit TRAPPC complexes II and III
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21453443
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC8 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific TRAPPC8 interactions are better
      represented as TRAPP/TRAPPIII complex membership, TBC1D14/TRAPPIII
      autophagy context, or TMEM131-dependent collagen cargo transport.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - PMID:32095531
    supported_by:
    - &id002
      reference_id: PMID:21525244
      supporting_text: These results firmly establish the newly identified
        proteins as stable TRAPP interactors
    - &id003
      reference_id: PMID:26711178
      supporting_text: is required for TBC1D14 to bind TRAPPIII
    - &id004
      reference_id: PMID:32095531
      supporting_text: mCherry-tagged TMEM131 Ct specifically pulled down the
        GFP-tagged TRAPPC8 fragment
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC8 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific TRAPPC8 interactions are better
      represented as TRAPP/TRAPPIII complex membership, TBC1D14/TRAPPIII
      autophagy context, or TMEM131-dependent collagen cargo transport.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - PMID:32095531
    supported_by:
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: located_in
  review:
    summary: cytoplasm localization is consistent with TRAPPC8/TRAPPIII
      trafficking biology.
    action: ACCEPT
    reason: Accept as a supported location/context for TRAPPC8-containing TRAPP
      reactions.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - Reactome:R-HSA-8877475
    supported_by:
    - *id005
    - *id001
    - *id006
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: TRAPPC8 participates in ER-to-Golgi trafficking through
      TRAPP/TRAPPIII.
    action: ACCEPT
    reason: Accept as a core process. TRAPPC8 depletion affects Golgi/secretory
      traffic and TRAPPC8-containing TRAPP III transports collagen cargo from ER
      to Golgi.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - PMID:32095531
    supported_by:
    - *id005
    - &id013
      reference_id: PMID:26711178
      supporting_text: TRAPPC8 modulates autophagy and secretory trafficking
    - &id007
      reference_id: PMID:32095531
      supporting_text: TRAPPC8-containing TRAPP III is critical for the
        ER-to-Golgi transport of collagen cargos
- term:
    id: GO:0048208
    label: COPII vesicle coat assembly
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The COPII annotation captures cargo transport context but
      overstates TRAPPC8 as a coat-assembly factor.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC8/TRAPP III
      promotes ER-to-Golgi transport of collagen cargo in COPII context, but the
      evidence does not show TRAPPC8 assembling the COPII coat.
    proposed_replacement_terms:
    - &id008
      id: GO:0006888
      label: endoplasmic reticulum to Golgi vesicle-mediated transport
    additional_reference_ids:
    - PMID:32095531
    - Reactome:R-HSA-8877475
    supported_by:
    - *id007
    - &id012
      reference_id: PMID:32095531
      supporting_text: C-terminal recruitment of TRAPP III for the ER-to-Golgi
        transport of collagen cargo
    - reference_id: Reactome:R-HSA-8877475
      supporting_text: TRAPPCII is recruited to ER-derived vesicles by virtue of
        an interaction between the TRAPPCII component TRAPPC3 and the COPII coat
        protein SEC23
- term:
    id: GO:0099022
    label: obsolete vesicle tethering
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The obsolete vesicle-tethering annotation should not be retained
      as-is.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported
      TRAPPC8/TRAPP process. Mammalian TRAPP tethering remains unresolved and
      this term is obsolete.
    proposed_replacement_terms:
    - *id008
    additional_reference_ids:
    - PMID:27066478
    - PMID:21525244
    - PMID:32095531
    supported_by:
    - reference_id: PMID:27066478
      supporting_text: evidence that any TRAPP complex acts as a membrane tether
        is currently inconclusive
    - *id005
    - *id007
- term:
    id: GO:1990072
    label: TRAPPIII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC8 is a TRAPPIII-associated Trs85 ortholog.
    action: ACCEPT
    reason: Accept as core complex membership. TRAPPC8 is the mammalian Trs85
      ortholog and is directly implicated in mammalian TRAPPIII-like/autophagy
      and secretory trafficking complexes.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - *id009
    - *id001
    - *id010
    - *id011
- term:
    id: GO:0032964
    label: collagen biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:32095531
  qualifier: involved_in
  review:
    summary: TRAPPC8 supports collagen cargo transport, but collagen
      biosynthesis is too broad and mechanistically imprecise.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport. The paper supports
      TRAPPC8-dependent collagen cargo trafficking via TMEM131/TRAPP III, not
      direct collagen biosynthetic chemistry.
    proposed_replacement_terms:
    - *id008
    additional_reference_ids:
    - PMID:32095531
    supported_by:
    - *id007
    - *id012
    - reference_id: PMID:32095531
      supporting_text: RNAi-mediated depletion of expression of trpp-8, the C.
        elegans homolog of TRAPPC8, strongly reduced the abundance of
        COL-19::GFP
- term:
    id: GO:0007030
    label: Golgi organization
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: involved_in
  review:
    summary: Golgi organization is a direct TRAPPC8-depletion phenotype but is
      secondary to early secretory trafficking.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. Golgi fragmentation is a useful readout of
      TRAPPC8/TRAPP early secretory pathway disruption, while the core process
      is ER-to-Golgi/TRAPPIII trafficking.
    additional_reference_ids:
    - PMID:21525244
    supported_by:
    - *id005
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21525244
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC8 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific TRAPPC8 interactions are better
      represented as TRAPP/TRAPPIII complex membership, TBC1D14/TRAPPIII
      autophagy context, or TMEM131-dependent collagen cargo transport.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    - PMID:32095531
    supported_by:
    - *id002
    - *id003
    - *id004
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IDA
  original_reference_id: PMID:21525244
  qualifier: part_of
  review:
    summary: TRAPPC8 is a bona fide mammalian TRAPP subunit.
    action: ACCEPT
    reason: Accept as TRAPP complex membership. TRAPPC8/KIAA1012 copurifies with
      TRAPP components and is part of mammalian TRAPPIII-like biology.
    additional_reference_ids:
    - PMID:21525244
    - PMID:26711178
    supported_by:
    - reference_id: PMID:21525244
      supporting_text: C8 (KIAA1012) was found to copurify with TAP-C3
    - *id002
    - *id001
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8877475
  qualifier: located_in
  review:
    summary: cytosol localization is consistent with TRAPPC8/TRAPPIII
      trafficking biology.
    action: ACCEPT
    reason: Accept as a supported location/context for TRAPPC8-containing TRAPP
      reactions.
    additional_reference_ids:
    - Reactome:R-HSA-8877475
    - PMID:26711178
    supported_by:
    - *id006
    - *id001
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IMP
  original_reference_id: PMID:26711178
  qualifier: involved_in
  review:
    summary: TRAPPC8-containing mammalian TRAPPIII regulates bulk macroautophagy
      through ATG9 trafficking.
    action: NEW
    reason: Add as a new direct process annotation. TRAPPC8 is specifically
      shown to modulate autophagy and maintain ATG9 cycling needed for autophagy
      initiation.
    additional_reference_ids:
    - PMID:26711178
    - Reactome:R-HSA-8877475
    supported_by:
    - reference_id: PMID:26711178
      supporting_text: TRAPPC8 modulates autophagy and secretory trafficking
    - reference_id: PMID:26711178
      supporting_text: maintaining the cycling pool of ATG9 required for
        initiation of autophagy
    - reference_id: PMID:26711178
      supporting_text: Our findings are the first to clearly characterise a role
        for mammalian TRAPP, in particular TRAPPC8, in bulk macroautophagy
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: PMID:21453443
  title: Organization and assembly of the TRAPPII complex.
  findings: []
- id: PMID:21525244
  title: C4orf41 and TTC-15 are mammalian TRAPP components with a role at an
    early stage in ER-to-Golgi trafficking.
  findings: []
- id: PMID:27066478
  title: TRAPP Complexes in Secretion and Autophagy.
  findings: []
- id: PMID:32095531
  title: Broadly conserved roles of TMEM131 family proteins in intracellular
    collagen assembly and secretory cargo trafficking.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the
    human interactome.
  findings: []
- id: Reactome:R-HSA-8877475
  title: TRAPPC complexes exchange GTP for GDP on RAB1
  findings: []
- id: PMID:26711178
  title: TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic.
  findings: []
core_functions:
- contributes_to_molecular_function:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  in_complex:
    id: GO:1990072
    label: TRAPPIII protein complex
  description: TRAPPC8 contributes the Trs85-like TRAPPIII subunit to TRAPP/RAB1
    trafficking. This supports ER-to-Golgi transport, ATG9 cycling needed for
    autophagy initiation, and collagen-cargo trafficking in TMEM131/TRAPP III
    contexts. It should be modeled as contributing to TRAPPIII/TRAPP complex
    activity rather than independently enabling GEF activity.
  directly_involved_in:
  - id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  - id: GO:0006914
    label: autophagy
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005794
    label: Golgi apparatus
  supported_by:
  - *id001
  - *id013
  - reference_id: PMID:26711178
    supporting_text: maintaining the cycling pool of ATG9 required for
      initiation of autophagy
  - reference_id: PMID:26711178
    supporting_text: Our findings are the first to clearly characterise a role
      for mammalian TRAPP, in particular TRAPPC8, in bulk macroautophagy
  - *id005
  - *id007
  - *id006
  - *id011
proposed_new_terms: []
suggested_questions:
- question: Should TRAPPC8 receive a direct autophagy or ATG9 trafficking
    annotation in GOA based on PMID:26711178?
  experts:
  - GO autophagy editors
  - Sharon A. Tooze
- question: Should the collagen biosynthetic process annotation for TRAPPC8 be
    replaced by ER-to-Golgi vesicle-mediated transport with collagen-cargo
    context?
  experts:
  - GO extracellular matrix editors
  - GO transport editors
- question: Should TRAPPC8 be curated primarily as a TRAPPIII-specific subunit
    rather than a generic TRAPP-complex component in human?
  experts:
  - ComplexPortal curators
  - Reactome TRAPP curators
suggested_experiments:
- description: Deplete or rescue TRAPPC8 in mammalian cells and quantify ATG9
    cycling, omegasome formation, LC3/WIPI2 puncta, and RAB1 activation.
  experiment_type: autophagy trafficking rescue assay
  hypothesis: TRAPPC8-containing TRAPPIII promotes autophagy initiation by
    maintaining ATG9 cycling through RAB1-dependent trafficking.
- description: Reconstitute TRAPPC8-containing TRAPPIII with and without TBC1D14
    or TMEM131 fragments and measure RAB1 exchange plus cargo membrane
    recruitment.
  experiment_type: complex reconstitution and RAB1 GEF assay
  hypothesis: TRAPPC8 enables adaptor/cargo-specific recruitment of TRAPPIII
    while contributing to complex-level RAB1 GEF activity.
- description: Compare collagen secretion, VSVG ER-Golgi transport, and
    autophagy initiation in TRAPPC8 mutant/rescue cells to separate
    cargo-specific and general trafficking roles.
  experiment_type: parallel cargo-trafficking assay
  hypothesis: TRAPPC8 supports both general TRAPPIII ER-Golgi traffic and
    specialized collagen/ATG9 cargo routes.