id: Q8IUR0 gene_symbol: TRAPPC5 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- TRAPPC5 is the human Trs31 ortholog and a small TRAPP core subunit. It supports TRAPP complex architecture, complex-level RAB1 guanine-nucleotide exchange, and ER-to-Golgi vesicle-mediated transport. Autophagy-related effects are best understood through TRAPP/TRAPPII/TRAPPIII complex membership and ER-Golgi trafficking rather than an independent TRAPPC5-specific autophagy function. existing_annotations: - term: id: GO:1990071 label: TRAPPII protein complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: TRAPPC5 is represented in TRAPPII protein complex through the shared TRAPP core. action: ACCEPT reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit. additional_reference_ids: - PMID:21525244 - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - &id001 reference_id: PMID:21525244 supporting_text: with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b - &id002 reference_id: PMID:27066478 supporting_text: TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13 - &id003 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:1990072 label: TRAPPIII protein complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: TRAPPC5 is represented in TRAPPIII protein complex through the shared TRAPP core. action: ACCEPT reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit. additional_reference_ids: - PMID:21525244 - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - *id001 - *id002 - *id003 - 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: TRAPPC5 contributes to TRAPP-dependent ER-to-Golgi trafficking. action: ACCEPT reason: Accept as a core process. TRAPPC5 is a core TRAPP subunit, and TRAPP complex/RAB1 biology supports ER-to-Golgi vesicle-mediated transport. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 supported_by: - &id006 reference_id: PMID:21525244 supporting_text: in ER-to-Golgi trafficking at a very early stage - &id004 reference_id: Reactome:R-HSA-5694439 supporting_text: TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic - &id007 reference_id: Reactome:R-HSA-5694409 supporting_text: The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it - term: id: GO:1990070 label: TRAPPI protein complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: TRAPPI protein complex is problematic as a human TRAPPC5 annotation. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. TRAPPC5 is a yeast TRAPP I core ortholog, but the mammalian literature questions the existence of a discrete TRAPP I complex in vivo. additional_reference_ids: - PMID:21525244 - PMID:27066478 supported_by: - reference_id: PMID:21525244 supporting_text: absence of a TRAPP I-equivalent complex in mammalian cells - reference_id: PMID:27066478 supporting_text: TRAPP I cannot be separated from the mammalian TRAPP II and its existence in vivo in mammalian cells is currently in question - reference_id: PMID:27066478 supporting_text: there is currently no evidence for the existence of TRAPP I in mammalian cells - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: endoplasmic reticulum localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 supported_by: - &id005 reference_id: PMID:21525244 supporting_text: known human TRAPP components, including C3, C4, and C5 - *id004 - 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 TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 supported_by: - *id005 - *id004 - term: id: GO:0030008 label: TRAPP complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: TRAPPC5 is a human TRAPP core subunit. action: ACCEPT reason: Accept as core cellular-component membership. Mammalian TRAPP component work identifies C5/TRAPPC5 among known human TRAPP components. additional_reference_ids: - PMID:21525244 - PMID:27066478 supported_by: - *id001 - *id005 - &id010 reference_id: PMID:27066478 supporting_text: A single TRAPP complex purified from mammalian cell lysate contains all the known subunits - term: id: GO:0048193 label: Golgi vesicle transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: Golgi vesicle transport is plausible TRAPP context but less specific than ER-to-Golgi transport for TRAPPC5. action: KEEP_AS_NON_CORE reason: Keep as non-core. The core process is ER-to-Golgi/TRAPP/RAB1 transport; broader Golgi vesicle transport is a reasonable parent/context but not the most specific function. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 supported_by: - *id006 - *id004 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Generic protein binding is not informative for TRAPPC5 function. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding. additional_reference_ids: - PMID:21525244 supported_by: - *id005 - 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 TRAPPC5 function. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding. additional_reference_ids: - PMID:21525244 supported_by: - *id005 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: Generic protein binding is not informative for TRAPPC5 function. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding. additional_reference_ids: - PMID:21525244 supported_by: - *id005 - 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 TRAPPC5 function. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding. additional_reference_ids: - PMID:21525244 supported_by: - *id005 - 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 TRAPPC5 function. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding. additional_reference_ids: - PMID:21525244 supported_by: - *id005 - term: id: GO:0005737 label: cytoplasm evidence_type: NAS original_reference_id: PMID:27066478 qualifier: located_in review: summary: cytoplasm localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 supported_by: - *id005 - *id004 - 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: TRAPPC5 contributes to TRAPP-dependent ER-to-Golgi trafficking. action: ACCEPT reason: Accept as a core process. TRAPPC5 is a core TRAPP subunit, and TRAPP complex/RAB1 biology supports ER-to-Golgi vesicle-mediated transport. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 supported_by: - *id006 - *id004 - *id007 - term: id: GO:0006901 label: vesicle coat assembly evidence_type: NAS original_reference_id: PMID:27066478 qualifier: involved_in review: summary: vesicle coat assembly overstates TRAPPC5 as a coat-assembly factor. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC5 participates in TRAPP-dependent trafficking, but the evidence does not show direct coat assembly by TRAPPC5. proposed_replacement_terms: - &id008 id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id006 - *id004 - &id009 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: COPII vesicle coat assembly overstates TRAPPC5 as a coat-assembly factor. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC5 participates in TRAPP-dependent trafficking, but the evidence does not show direct coat assembly by TRAPPC5. proposed_replacement_terms: - *id008 additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id006 - *id004 - *id009 - 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 kept as-is for TRAPPC5. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC5/TRAPP process. Mammalian TRAPP tethering remains unresolved and the term is obsolete. proposed_replacement_terms: - *id008 additional_reference_ids: - PMID:27066478 - PMID:21525244 - 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 - *id006 - *id004 - term: id: GO:1990071 label: TRAPPII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC5 is represented in TRAPPII protein complex through the shared TRAPP core. action: ACCEPT reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit. additional_reference_ids: - PMID:21525244 - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - *id001 - *id002 - *id003 - term: id: GO:1990072 label: TRAPPIII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC5 is represented in TRAPPIII protein complex through the shared TRAPP core. action: ACCEPT reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit. additional_reference_ids: - PMID:21525244 - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - *id001 - *id002 - *id003 - term: id: GO:0030008 label: TRAPP complex evidence_type: IDA original_reference_id: PMID:21525244 qualifier: part_of review: summary: TRAPPC5 is a human TRAPP core subunit. action: ACCEPT reason: Accept as core cellular-component membership. Mammalian TRAPP component work identifies C5/TRAPPC5 among known human TRAPP components. additional_reference_ids: - PMID:21525244 - PMID:27066478 supported_by: - *id001 - *id005 - *id010 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694409 qualifier: located_in review: summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id007 - *id004 - *id003 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694418 qualifier: located_in review: summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id007 - *id004 - *id003 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694439 qualifier: located_in review: summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id007 - *id004 - *id003 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694441 qualifier: located_in review: summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id007 - *id004 - *id003 - 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 TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id007 - *id004 - *id003 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:0000120 title: Combined Automated Annotation using Multiple IEA Methods 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:25416956 title: A proteome-scale map of the human interactome network. 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:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. 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: 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-8877475 title: TRAPPC complexes exchange GTP for GDP on RAB1 findings: [] core_functions: - contributes_to_molecular_function: id: GO:0005085 label: guanyl-nucleotide exchange factor activity in_complex: id: GO:0030008 label: TRAPP complex description: TRAPPC5 contributes the Trs31-like small core subunit to TRAPP complexes, supporting complex-level RAB1 guanine-nucleotide exchange and ER-to-Golgi trafficking. It should be modeled as contributing to the TRAPP complex activity rather than independently enabling GEF 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: - *id001 - *id005 - reference_id: PMID:21525244 supporting_text: These activities are dependent on the subunits Bet3p, Trs31p, Trs23p, and Bet5p - *id007 - *id003 - *id006 - *id004 proposed_new_terms: [] suggested_questions: - question: Should TRAPPC5 receive a contributes_to RAB1 guanine-nucleotide exchange factor activity annotation based on Trs31-dependent yeast GEF evidence plus mammalian TRAPP complex models? experts: - GO transport editors - Reactome TRAPP curators - question: Should human TRAPPI protein complex annotations be removed or replaced when the literature questions a discrete mammalian TRAPP I complex? experts: - GO cellular-component editors - ComplexPortal curators - question: Should PN TRAPP-component autophagy context be represented only by TRAPPIII membership for TRAPPC5 unless TRAPPC5-specific autophagy experiments are available? experts: - GO autophagy editors - TRAPP biology experts suggested_experiments: - description: Reconstitute TRAPPC5-containing human TRAPP complexes and measure RAB1 GDP-GTP exchange after TRAPPC5 depletion or interface mutation. experiment_type: complex reconstitution and RAB1 GEF assay hypothesis: TRAPPC5 is required as a core TRAPP subunit for complex-level RAB1 GEF activity. - description: Use TRAPPC5 knockout/rescue cells to assay ER-to-Golgi cargo transport, TRAPP complex stability, and Golgi/ER localization of TRAPP subunits. experiment_type: cellular trafficking rescue assay hypothesis: TRAPPC5 loss disrupts TRAPP-dependent ER-to-Golgi vesicle-mediated transport by destabilizing or mislocalizing the TRAPP core. - description: Biochemically separate human TRAPPII and TRAPPIII pools containing TRAPPC5 and test whether any discrete TRAPPI-like pool exists in vivo. experiment_type: complex purification and native fractionation hypothesis: TRAPPC5 is present in human TRAPPII/TRAPPIII assemblies, while a discrete mammalian TRAPPI complex is absent or not stable in vivo.