id: Q9Y5R8 gene_symbol: TRAPPC1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- TRAPPC1 is a small core subunit of the transport protein particle (TRAPP) complex. It contributes to TRAPP complex architecture and complex-level RAB1 guanine-nucleotide exchange/vesicle-trafficking functions, especially ER-to-Golgi vesicle-mediated transport. Autophagy component recruitment is best understood through TRAPP/TRAPPII/TRAPPIII complex membership rather than independent TRAPPC1 activity. existing_annotations: - term: id: GO:0030008 label: TRAPP complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: TRAPPC1 is a core subunit of the TRAPP complex, and this cellular-component annotation captures the strongest gene-level function. action: ACCEPT reason: Accept as core. Direct structural and review evidence place TRAPPC1/Mum2 in the conserved TRAPP core, and the PN mapping also resolves the autophagy-contextual leaf to TRAPP complex membership. additional_reference_ids: - PMID:16828797 - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - &id005 reference_id: PMID:16828797 supporting_text: crystal structure of a human Bet3-Tpc6B heterodimer, which represents a core sub-complex in the assembly of TRAPP - &id006 reference_id: PMID:16828797 supporting_text: Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further TRAPP subunit - &id001 reference_id: PMID:27066478 supporting_text: TRAPP is a highly conserved modular multi-subunit protein complex - &id007 reference_id: PMID:27066478 supporting_text: Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1 - term: id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: TRAPPC1 contributes to TRAPP-mediated ER-to-Golgi vesicle-mediated transport. action: ACCEPT reason: Accept as a core process. TRAPPC complexes activate RAB1 and facilitate ER-to-Golgi traffic, and TRAPPC1 is a core TRAPP subunit. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 - Reactome:R-HSA-8877475 supported_by: - &id003 reference_id: PMID:27066478 supporting_text: Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport - &id004 reference_id: Reactome:R-HSA-5694439 supporting_text: TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic - &id002 reference_id: Reactome:R-HSA-5694409 supporting_text: The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it - &id008 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:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: TRAPPC1 is a cytoplasmic/cytosolic TRAPP subunit associated with membrane-trafficking complexes. action: ACCEPT reason: Accept as a broad supported cellular location for a peripheral trafficking-complex subunit. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694409 supported_by: - *id001 - *id002 - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: TRAPPC1 participates in ER-derived vesicle trafficking and UniProt maps it to the endoplasmic reticulum. action: ACCEPT reason: Accept as a supported location for the ER-to-Golgi trafficking context. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 supported_by: - *id003 - *id004 - &id010 reference_id: Reactome:R-HSA-5694439 supporting_text: TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23 - term: id: GO:0005794 label: Golgi apparatus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: TRAPPC1 participates in ER-to-Golgi transport and is associated with Golgi/cis-Golgi TRAPP trafficking functions. action: ACCEPT reason: Accept as a supported Golgi-location annotation for TRAPP-mediated ER-to-Golgi trafficking. Falcon deep research corroborates Golgi/ER-Golgi-interface localization for TRAPPC1 as part of TRAPP complexes (with cis-Golgi labeling reported for TRAPP-specific subunits in Drosophila). additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 - file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md supported_by: - *id003 - *id004 - &id015 reference_id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md supporting_text: TRAPPC1, as part of TRAPP complexes, localizes primarily to the Golgi apparatus and the endoplasmic reticulum (ER)-Golgi interface - term: id: GO:0016192 label: vesicle-mediated transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: Vesicle-mediated transport is true but too broad for TRAPPC1; the evidence supports the ER-to-Golgi/TRAPP/RAB1 pathway more specifically. action: MODIFY reason: Modify to the more specific ER-to-Golgi vesicle-mediated transport term. proposed_replacement_terms: - &id009 id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 supported_by: - *id003 - *id004 - *id002 - term: id: GO:0030008 label: TRAPP complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: TRAPPC1 is a core subunit of the TRAPP complex, and this cellular-component annotation captures the strongest gene-level function. action: ACCEPT reason: Accept as core. Direct structural and review evidence place TRAPPC1/Mum2 in the conserved TRAPP core, and the PN mapping also resolves the autophagy-contextual leaf to TRAPP complex membership. additional_reference_ids: - PMID:16828797 - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - *id005 - *id006 - *id001 - *id007 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: Generic protein binding is not informative for TRAPPC1. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than GO:0005515. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Generic protein binding is not informative for TRAPPC1. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than GO:0005515. - 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 TRAPPC1. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than GO:0005515. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: Generic protein binding is not informative for TRAPPC1. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than GO:0005515. - term: id: GO:0005737 label: cytoplasm evidence_type: NAS original_reference_id: PMID:27066478 qualifier: located_in review: summary: TRAPPC1 is a cytoplasmic/cytosolic TRAPP subunit associated with membrane-trafficking complexes. action: ACCEPT reason: Accept as a broad supported cellular location for a peripheral trafficking-complex subunit. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694409 supported_by: - *id001 - *id002 - 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: TRAPPC1 contributes to TRAPP-mediated ER-to-Golgi vesicle-mediated transport. action: ACCEPT reason: Accept as a core process. TRAPPC complexes activate RAB1 and facilitate ER-to-Golgi traffic, and TRAPPC1 is a core TRAPP subunit. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 - Reactome:R-HSA-8877475 supported_by: - *id003 - *id004 - *id002 - *id008 - &id014 reference_id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md supporting_text: TRAPPIII activates Rab1 to regulate transport of newly synthesized proteins from the ER to the Golgi apparatus - term: id: GO:0006901 label: vesicle coat assembly evidence_type: NAS original_reference_id: PMID:27066478 qualifier: involved_in review: summary: TRAPPC complexes interact with vesicle coats and RAB1 on ER-derived vesicles, but TRAPPC1 is not a coat-assembly factor. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport. The coat-related evidence supports recruitment/traffic context rather than direct vesicle coat assembly. proposed_replacement_terms: - *id009 additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id010 - &id011 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:0048208 label: COPII vesicle coat assembly evidence_type: NAS original_reference_id: PMID:27066478 qualifier: involved_in review: summary: The COPII evidence places TRAPPCII near SEC23/COPII vesicles, but does not show TRAPPC1 assembling the COPII coat. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport, which captures the supported TRAPP/COPII/RAB1 trafficking role without overclaiming coat assembly. proposed_replacement_terms: - *id009 additional_reference_ids: - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id010 - *id011 - term: id: GO:0099022 label: obsolete vesicle tethering evidence_type: NAS original_reference_id: PMID:27066478 qualifier: involved_in review: summary: This annotation uses an obsolete vesicle-tethering term, and the cited TRAPP review cautions that direct TRAPP tethering evidence is inconclusive. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport, the safer supported process for TRAPPC1/TRAPP complex function. proposed_replacement_terms: - *id009 additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-5694439 supported_by: - reference_id: PMID:27066478 supporting_text: evidence that any TRAPP complex acts as a membrane tether is currently inconclusive - *id004 - term: id: GO:1990071 label: TRAPPII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC1 is represented in human TRAPPII complex models and ComplexPortal annotations. action: ACCEPT reason: Accept as a supported TRAPP complex subtype membership, while recognizing that gene-level process conclusions should remain centered on ER-Golgi transport and TRAPP/RAB1 function. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - *id001 - *id007 - *id008 - &id013 reference_id: Reactome:R-HSA-8877475 supporting_text: Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind - term: id: GO:1990072 label: TRAPPIII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC1 is represented in human TRAPPIII complex models; this is the TRAPP subtype most relevant to the PN autophagy recruitment context. action: ACCEPT reason: Accept as supported complex membership. The autophagy implication should be treated as context for TRAPPIII/RAB1 biology, not as a broad autophagy BP annotation for TRAPPC1. Falcon deep research likewise links autophagosome formation to the TRAPPIII holo-complex rather than to TRAPPC1 specifically. additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-8877475 - file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md supported_by: - *id001 - *id007 - 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 - reference_id: PMID:27066478 supporting_text: the connection of the mammalian TRAPP III complex to autophagy is currently not clear - reference_id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md supporting_text: TRAPPIII has been localized to autophagy-related membranes where it participates in autophagosome formation - term: id: GO:0005576 label: extracellular region evidence_type: TAS original_reference_id: Reactome:R-HSA-6798751 qualifier: located_in review: summary: The extracellular-region annotation comes from a broad Reactome neutrophil-degranulation event and is not supported as a core TRAPPC1 localization. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. TRAPPC1 is a TRAPP trafficking-complex subunit associated with cytosol/ER/Golgi contexts, not a secreted extracellular protein. additional_reference_ids: - Reactome:R-HSA-6798751 supported_by: - &id012 reference_id: Reactome:R-HSA-6798751 supporting_text: Azurophil or primary granules were originally defined by their high content of myeloperoxidase - term: id: GO:0035578 label: azurophil granule lumen evidence_type: TAS original_reference_id: Reactome:R-HSA-6798751 qualifier: located_in review: summary: The azurophil-granule-lumen annotation is inherited from a broad Reactome degranulation context and lacks TRAPPC1-specific support. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. It does not fit the core TRAPPC1/TRAPP complex localization or trafficking function. additional_reference_ids: - Reactome:R-HSA-6798751 supported_by: - *id012 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694409 qualifier: located_in review: summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions. action: ACCEPT reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id004 - *id002 - *id008 - *id013 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694418 qualifier: located_in review: summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions. action: ACCEPT reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id004 - *id002 - *id008 - *id013 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694439 qualifier: located_in review: summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions. action: ACCEPT reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id004 - *id002 - *id008 - *id013 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694441 qualifier: located_in review: summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions. action: ACCEPT reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id004 - *id002 - *id008 - *id013 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8877475 qualifier: located_in review: summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions. action: ACCEPT reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id004 - *id002 - *id008 - *id013 references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - 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: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:27066478 title: TRAPP Complexes in Secretion and Autophagy. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: Reactome:R-HSA-5694409 title: Nucleotide exchange on RAB1 findings: [] - id: Reactome:R-HSA-5694418 title: RAB1:GTP binds USO1 and GORASP1:GOLGA2 findings: [] - id: Reactome:R-HSA-5694439 title: COPII coat binds TRAPPCII and RAB1:GDP findings: [] - id: Reactome:R-HSA-5694441 title: CSNK1D phosphorylates SEC23 findings: [] - id: Reactome:R-HSA-6798751 title: Exocytosis of azurophil granule lumen proteins findings: [] - id: Reactome:R-HSA-8877475 title: TRAPPC complexes exchange GTP for GDP on RAB1 findings: [] - id: PMID:16828797 title: 'Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric complexes with Bet3 and Mum2.' findings: [] - id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md title: Falcon deep research report for TRAPPC1 findings: [] reference_review: relevance: MEDIUM correctness: UNVERIFIED review_notes: >- LLM-synthesized (Edison/Falcon) deep-research report compiling current understanding of TRAPPC1. Useful corroboration for established TRAPP-complex biology (core subunit membership with TRAPPC3/TRAPPC4 at the Rab-binding/GEF site; TRAPPIII activates RAB1 for ER-to-Golgi transport and autophagy; TRAPPII activates RAB11; Golgi/ER-Golgi and cis-Golgi localization). IMPORTANT caveat: the report repeatedly attributes whole-TRAPP holo-complex functions (GEF activity, Rab specificity, autophagosome formation) to the TRAPPC1 subunit specifically. Subunit-specific evidence for TRAPPC1 is limited to its structural placement in the conserved core (consistent with PMID:16828797 Bet3-Tpc6B-Mum2 sub-complex) and to patient-variant studies (Zykaj 2024; Van Bergen 2020) showing reduced TRAPPC1 destabilizes the complex and impairs trafficking/autophagy. GEF catalysis is a holo-complex property, not an independent TRAPPC1 activity. Citations are secondary reviews (Galindo & Munro 2023; Bagde & Fromme 2023; Sacher 2019; Hall 2024) not independently verified here. core_functions: - contributes_to_molecular_function: id: GO:0005085 label: guanyl-nucleotide exchange factor activity in_complex: id: GO:0030008 label: TRAPP complex description: TRAPPC1 contributes a small core subunit to TRAPP complexes, supporting complex-level RAB1 guanine-nucleotide exchange and ER-to-Golgi trafficking. Its role is best represented as contribution to the TRAPP complex activity rather than an independent catalytic activity. directly_involved_in: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport locations: - id: GO:0005829 label: cytosol - id: GO:0005737 label: cytoplasm - id: GO:0005783 label: endoplasmic reticulum - id: GO:0005794 label: Golgi apparatus supported_by: - *id005 - *id006 - *id003 - *id004 - *id002 - *id008 proposed_new_terms: [] suggested_questions: - question: Should TRAPPC1 and other shared TRAPP subunits receive contributes_to annotations for TRAPPC complex RAB1 guanine-nucleotide exchange activity? experts: - GO transport editors - Reactome TRAPP curators - question: Should TRAPP subunit PN autophagy contexts be captured only as TRAPPIII complex membership unless direct human autophagophore/PAS evidence is available? experts: - GO autophagy editors - GO cellular-component editors - question: Should current TRAPPC1 vesicle coat assembly and obsolete vesicle tethering annotations be replaced by ER-to-Golgi vesicle-mediated transport or more specific TRAPP/RAB1 terms? experts: - ComplexPortal curators - GO transport editors suggested_experiments: - description: Reconstitute human TRAPPII/TRAPPIII complexes with and without TRAPPC1 and measure RAB1 GDP-GTP exchange activity. experiment_type: complex reconstitution and RAB1 GEF assay hypothesis: TRAPPC1 is required as a core scaffold subunit for TRAPPC complex-level RAB1 GEF activity rather than acting as an independent catalytic subunit. - description: Use TRAPPC1 knockout and rescue cells to assay ER-to-Golgi cargo transport, COPII-vesicle association, and Golgi localization of TRAPP components. experiment_type: cellular trafficking rescue assay hypothesis: TRAPPC1 loss disrupts TRAPP-dependent ER-to-Golgi vesicle-mediated transport by destabilizing or mislocalizing TRAPP complexes. - description: Measure ATG9 localization and autophagophore initiation markers in TRAPPC1 rescue cells while separately monitoring ER-to-Golgi trafficking defects. experiment_type: autophagy-context separation assay hypothesis: Any TRAPPC1 autophagy phenotype is mediated through TRAPPIII/RAB1 trafficking context and should not be generalized to a broad autophagy core function without direct evidence.