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.