id: Q9Y296 gene_symbol: TRAPPC4 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- TRAPPC4/synbindin is a core TRAPP-complex subunit required for TRAPP assembly/stability, complex-level RAB1 guanine-nucleotide exchange, ER-to-Golgi trafficking, and autophagy. Human patient fibroblasts and yeast Trs23 models show both trafficking and autophagy defects when TRAPPC4/Trs23 levels are reduced. alternative_products: - name: '1' id: Q9Y296-1 - name: '2' id: Q9Y296-2 sequence_note: VSP_056348 existing_annotations: - term: id: GO:0030008 label: TRAPP complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. action: ACCEPT reason: Accept as core cellular-component membership. Direct TRAPPC4 evidence shows reduced TRAPPC4 destabilizes TRAPP complex assembly, and mammalian TRAPP sources identify TRAPPC4 among core subunits. additional_reference_ids: - PMID:31794024 - PMID:21525244 supported_by: - &id004 reference_id: PMID:31794024 supporting_text: TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes - &id005 reference_id: PMID:31794024 supporting_text: defect in TRAPP complex assembly and/or stability - &id006 reference_id: PMID:21525244 supporting_text: the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b - 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: TRAPPC4 is required for TRAPP-mediated ER-to-Golgi/Golgi trafficking. action: ACCEPT reason: Accept as a core process. TRAPPC4-deficient patient fibroblasts have delayed VSVG trafficking through the Golgi that is rescued by wild-type TRAPPC4. additional_reference_ids: - PMID:31794024 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 supported_by: - &id001 reference_id: PMID:31794024 supporting_text: significantly delayed entry into and exit from the Golgi - &id002 reference_id: Reactome:R-HSA-5694439 supporting_text: TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic - &id008 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:0000139 label: Golgi membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Golgi membrane localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - &id003 reference_id: PMID:11018053 supporting_text: present on membrane-bound cisterns and vesicles within the soma and dendrites - *id002 - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: cytoplasm localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - 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 TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0016192 label: vesicle-mediated transport evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in review: summary: Vesicle-mediated transport is true but too broad for TRAPPC4. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport, the specific supported TRAPPC4 trafficking process. proposed_replacement_terms: - &id009 id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport additional_reference_ids: - PMID:31794024 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id002 - term: id: GO:0030008 label: TRAPP complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. action: ACCEPT reason: Accept as core cellular-component membership. Direct TRAPPC4 evidence shows reduced TRAPPC4 destabilizes TRAPP complex assembly, and mammalian TRAPP sources identify TRAPPC4 among core subunits. additional_reference_ids: - PMID:31794024 - PMID:21525244 supported_by: - *id004 - *id005 - *id006 - term: id: GO:0031982 label: vesicle evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: vesicle localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0045211 label: postsynaptic membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: postsynaptic membrane reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. action: KEEP_AS_NON_CORE reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. additional_reference_ids: - PMID:11018053 supported_by: - &id007 reference_id: PMID:11018053 supporting_text: associated with synaptic membranes, mainly at the postsynaptic side - *id003 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17110339 qualifier: enables review: summary: TRAPP-subunit interaction evidence is better represented as TRAPP complex membership than generic protein binding. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. Protein binding does not capture the specific TRAPPC4 role in TRAPP complex architecture or trafficking. additional_reference_ids: - PMID:17110339 - PMID:31794024 supported_by: - reference_id: PMID:17110339 supporting_text: composed of seven subunits involved in ER-to-Golgi trafficking - *id004 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21826244 qualifier: enables review: summary: TRAPPC4 binds ERK2 in CRC signaling assays, but generic protein binding is not an informative gene function. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The specific ERK2/MAPK signaling context may be biologically interesting but should not be represented as generic protein binding in a core PN review. additional_reference_ids: - PMID:21826244 supported_by: - reference_id: PMID:21826244 supporting_text: TRAPPC4 was found to bind with ERK2 - term: id: GO:0005795 label: Golgi stack evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Golgi stack localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0008021 label: synaptic vesicle evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: synaptic vesicle is more specific than the available synbindin localization evidence supports. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The source supports membrane cisterns/vesicles and mainly postsynaptic synaptic membranes, not this precise synaptic subcompartment as a core TRAPPC4 location. additional_reference_ids: - PMID:11018053 supported_by: - *id003 - *id007 - term: id: GO:0016358 label: dendrite development evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Dendrite development is broader and more causal than the synbindin evidence supports. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The original neuronal paper discusses possible spine morphogenesis roles but explicitly leaves synbindin effector status unresolved. additional_reference_ids: - PMID:11018053 supported_by: - &id014 reference_id: PMID:11018053 supporting_text: the clustering of synbindin in spines requires syndecan-2 expression - &id015 reference_id: PMID:11018053 supporting_text: At present, we do not know whether synbindin acts as a downstream effector - term: id: GO:0030425 label: dendrite evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: dendrite reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. action: KEEP_AS_NON_CORE reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. additional_reference_ids: - PMID:11018053 supported_by: - *id007 - *id003 - term: id: GO:0045202 label: synapse evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: synapse reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. action: KEEP_AS_NON_CORE reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. additional_reference_ids: - PMID:11018053 supported_by: - *id007 - *id003 - term: id: GO:0048786 label: presynaptic active zone evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: is_active_in review: summary: presynaptic active zone is more specific than the available synbindin localization evidence supports. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The source supports membrane cisterns/vesicles and mainly postsynaptic synaptic membranes, not this precise synaptic subcompartment as a core TRAPPC4 location. additional_reference_ids: - PMID:11018053 supported_by: - *id003 - *id007 - term: id: GO:0098839 label: postsynaptic density membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: is_active_in review: summary: postsynaptic density membrane is more specific than the available synbindin localization evidence supports. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The source supports membrane cisterns/vesicles and mainly postsynaptic synaptic membranes, not this precise synaptic subcompartment as a core TRAPPC4 location. additional_reference_ids: - PMID:11018053 supported_by: - *id003 - *id007 - term: id: GO:0005737 label: cytoplasm evidence_type: NAS original_reference_id: PMID:27066478 qualifier: located_in review: summary: cytoplasm localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *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: TRAPPC4 is required for TRAPP-mediated ER-to-Golgi/Golgi trafficking. action: ACCEPT reason: Accept as a core process. TRAPPC4-deficient patient fibroblasts have delayed VSVG trafficking through the Golgi that is rescued by wild-type TRAPPC4. additional_reference_ids: - PMID:31794024 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 supported_by: - *id001 - *id002 - *id008 - 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 TRAPPC4 as a coat-assembly factor. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC4 affects TRAPP-dependent trafficking, but the evidence does not show direct vesicle coat assembly by TRAPPC4. proposed_replacement_terms: - *id009 additional_reference_ids: - PMID:31794024 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id001 - *id002 - &id010 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 TRAPPC4 as a coat-assembly factor. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC4 affects TRAPP-dependent trafficking, but the evidence does not show direct vesicle coat assembly by TRAPPC4. proposed_replacement_terms: - *id009 additional_reference_ids: - PMID:31794024 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id001 - *id002 - *id010 - 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, which captures the supported TRAPPC4/TRAPP trafficking role without relying on an obsolete term or unresolved tethering evidence. proposed_replacement_terms: - *id009 additional_reference_ids: - PMID:27066478 - PMID:31794024 - 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 - *id001 - *id002 - term: id: GO:1990071 label: TRAPPII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC4 is part of TRAPPII protein complex through the shared TRAPP core. action: ACCEPT reason: Accept as complex-context membership. TRAPPC4 is a core subunit required for TRAPP assembly/stability, and the core participates in TRAPPII/TRAPPIII holocomplexes. additional_reference_ids: - PMID:31794024 - PMID:27066478 supported_by: - &id011 reference_id: PMID:31794024 supporting_text: This TRAPP core then interacts with a number of accessory proteins to form two distinct, yet related complexes called TRAPP II - &id012 reference_id: PMID:31794024 supporting_text: affects the assembly of the core TRAPP complex and likely affects assembly of TRAPP II and TRAPP III in yeast - term: id: GO:1990072 label: TRAPPIII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC4 is part of TRAPPIII protein complex through the shared TRAPP core. action: ACCEPT reason: Accept as complex-context membership. TRAPPC4 is a core subunit required for TRAPP assembly/stability, and the core participates in TRAPPII/TRAPPIII holocomplexes. additional_reference_ids: - PMID:31794024 - PMID:27066478 supported_by: - *id011 - *id012 - term: id: GO:0000139 label: Golgi membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Golgi membrane localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: endoplasmic reticulum localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0031982 label: vesicle evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: vesicle localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0045211 label: postsynaptic membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: postsynaptic membrane reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. action: KEEP_AS_NON_CORE reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. additional_reference_ids: - PMID:11018053 supported_by: - *id007 - *id003 - term: id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport evidence_type: IMP original_reference_id: PMID:31794024 qualifier: involved_in review: summary: TRAPPC4 is required for TRAPP-mediated ER-to-Golgi/Golgi trafficking. action: ACCEPT reason: Accept as a core process. TRAPPC4-deficient patient fibroblasts have delayed VSVG trafficking through the Golgi that is rescued by wild-type TRAPPC4. additional_reference_ids: - PMID:31794024 - Reactome:R-HSA-5694439 - Reactome:R-HSA-5694409 supported_by: - *id001 - *id002 - *id008 - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:31794024 qualifier: involved_in review: summary: TRAPPC4 loss causes autophagy defects in patient fibroblasts and a yeast Trs23 model. action: ACCEPT reason: Accept as a direct PN-relevant process annotation. The term is broad, but the cited paper provides TRAPPC4-specific autophagic-flux and yeast autophagy-defect evidence. additional_reference_ids: - PMID:31794024 - PMID:27066478 supported_by: - &id016 reference_id: PMID:31794024 supporting_text: basal autophagy defect and a delay in autophagic flux - *id012 - reference_id: PMID:27066478 supporting_text: the connection of the mammalian TRAPP III complex to autophagy is currently not clear - term: id: GO:0030008 label: TRAPP complex evidence_type: IMP original_reference_id: PMID:31794024 qualifier: part_of review: summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. action: ACCEPT reason: Accept as core cellular-component membership. Direct TRAPPC4 evidence shows reduced TRAPPC4 destabilizes TRAPP complex assembly, and mammalian TRAPP sources identify TRAPPC4 among core subunits. additional_reference_ids: - PMID:31794024 - PMID:21525244 supported_by: - *id004 - *id005 - *id006 - term: id: GO:0030008 label: TRAPP complex evidence_type: IDA original_reference_id: PMID:21525244 qualifier: part_of review: summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. action: ACCEPT reason: Accept as core cellular-component membership. Direct TRAPPC4 evidence shows reduced TRAPPC4 destabilizes TRAPP complex assembly, and mammalian TRAPP sources identify TRAPPC4 among core subunits. additional_reference_ids: - PMID:31794024 - PMID:21525244 supported_by: - *id004 - *id005 - *id006 - 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 TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id008 - *id002 - &id013 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:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5694418 qualifier: located_in review: summary: cytosol localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id008 - *id002 - *id013 - 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 TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id008 - *id002 - *id013 - 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 TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id008 - *id002 - *id013 - 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 TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - Reactome:R-HSA-5694409 - Reactome:R-HSA-5694439 - Reactome:R-HSA-8877475 supported_by: - *id008 - *id002 - *id013 - term: id: GO:0005795 label: Golgi stack evidence_type: ISS original_reference_id: PMID:11018053 qualifier: located_in review: summary: Golgi stack localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. action: ACCEPT reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. additional_reference_ids: - PMID:31794024 - PMID:11018053 - Reactome:R-HSA-5694439 supported_by: - *id001 - *id003 - *id002 - term: id: GO:0008021 label: synaptic vesicle evidence_type: ISS original_reference_id: PMID:11018053 qualifier: located_in review: summary: synaptic vesicle is more specific than the available synbindin localization evidence supports. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The source supports membrane cisterns/vesicles and mainly postsynaptic synaptic membranes, not this precise synaptic subcompartment as a core TRAPPC4 location. additional_reference_ids: - PMID:11018053 supported_by: - *id003 - *id007 - term: id: GO:0016358 label: dendrite development evidence_type: ISS original_reference_id: PMID:11018053 qualifier: involved_in review: summary: Dendrite development is broader and more causal than the synbindin evidence supports. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The original neuronal paper discusses possible spine morphogenesis roles but explicitly leaves synbindin effector status unresolved. additional_reference_ids: - PMID:11018053 supported_by: - *id014 - *id015 - term: id: GO:0030425 label: dendrite evidence_type: ISS original_reference_id: PMID:11018053 qualifier: located_in review: summary: dendrite reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. action: KEEP_AS_NON_CORE reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. additional_reference_ids: - PMID:11018053 supported_by: - *id007 - *id003 - term: id: GO:0045202 label: synapse evidence_type: ISS original_reference_id: PMID:11018053 qualifier: located_in review: summary: synapse reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. action: KEEP_AS_NON_CORE reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. additional_reference_ids: - PMID:11018053 supported_by: - *id007 - *id003 references: - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity 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:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara 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:11018053 title: Synbindin, A novel syndecan-2-binding protein in neuronal dendritic spines. findings: [] - id: PMID:17110339 title: The architecture of the multisubunit TRAPP I complex suggests a model for vesicle tethering. 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:21826244 title: TRAPPC4-ERK2 interaction activates ERK1/2, modulates its nuclear localization and regulates proliferation and apoptosis of colorectal cancer cells. findings: [] - id: PMID:27066478 title: TRAPP Complexes in Secretion and Autophagy. findings: [] - id: PMID:31794024 title: Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability. 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: TRAPPC4 contributes a core subunit required for TRAPP complex assembly/stability, RAB1 guanine-nucleotide exchange, ER-to-Golgi trafficking, and autophagy. Its molecular role is best modeled as contribution to TRAPP complex GEF activity rather than independent catalysis. 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:0005783 label: endoplasmic reticulum - id: GO:0000139 label: Golgi membrane - id: GO:0005795 label: Golgi stack - id: GO:0031982 label: vesicle supported_by: - *id004 - reference_id: PMID:31794024 supporting_text: one of the essential subunits for guanine nucleotide exchange factor activity for Rab1 GTPase - *id005 - *id001 - *id016 - *id008 - *id002 proposed_new_terms: [] suggested_questions: - question: Should TRAPPC4 receive a contributes_to annotation for TRAPP complex RAB1 guanine-nucleotide exchange activity based on direct subunit-essential evidence? experts: - GO transport editors - Reactome TRAPP curators - question: Should TRAPPC4 autophagy be represented only by broad autophagy, or can the field support a more specific TRAPP/TRAPPIII-dependent autophagosome maturation term? experts: - GO autophagy editors - TRAPP/autophagy domain experts - question: Should neuronal synbindin annotations be kept as non-core human TRAPPC4 annotations or limited to experimentally tested rodent orthologs? experts: - GO synapse editors - GO transport editors suggested_experiments: - description: Reconstitute TRAPPC4-containing TRAPP core and TRAPPII/TRAPPIII complexes with TRAPPC4 depletion or interface mutants and measure RAB1 GDP-GTP exchange. experiment_type: complex reconstitution and RAB1 GEF assay hypothesis: TRAPPC4 is required as a core TRAPP subunit for complex-level RAB1 GEF activity and stable TRAPP holocomplex assembly. - description: Use TRAPPC4 patient fibroblast or knockout/rescue cells to assay VSVG ER-Golgi trafficking, TRAPP complex stability, and Golgi localization of TRAPP subunits in parallel. experiment_type: cellular trafficking rescue assay hypothesis: TRAPPC4 deficiency disrupts ER-to-Golgi vesicle-mediated transport by destabilizing TRAPP complexes. - description: Separate ER-Golgi traffic defects from autophagy defects in TRAPPC4 rescue cells by assaying ATG9 localization, autophagosome closure/flux, and VSVG trafficking side by side. experiment_type: autophagy and trafficking separation assay hypothesis: TRAPPC4 autophagy phenotypes are mediated through TRAPP complex assembly and TRAPPIII/RAB1 trafficking context.