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.
| 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. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport 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. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport 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. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport 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 |
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Download this section (compressed HTML)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
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
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