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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030008 TRAPP complex | IBA GO_REF:0000033 | ACCEPT | Summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. 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. Supporting Evidence: PMID:31794024 TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes PMID:31794024 defect in TRAPP complex assembly and/or stability PMID:21525244 the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: TRAPPC4 is required for TRAPP-mediated ER-to-Golgi/Golgi trafficking. Reason: Accept as a core process. TRAPPC4-deficient patient fibroblasts have delayed VSVG trafficking through the Golgi that is rescued by wild-type TRAPPC4. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi membrane localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: cytoplasm localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: endoplasmic reticulum localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000120 | MODIFY | Summary: Vesicle-mediated transport is true but too broad for TRAPPC4. Reason: Modify to ER-to-Golgi vesicle-mediated transport, the specific supported TRAPPC4 trafficking process. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0030008 TRAPP complex | IEA GO_REF:0000120 | ACCEPT | Summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. 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. Supporting Evidence: PMID:31794024 TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes PMID:31794024 defect in TRAPP complex assembly and/or stability PMID:21525244 the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b |
| GO:0031982 vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: vesicle localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: postsynaptic membrane reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. Reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. Supporting Evidence: PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites |
| GO:0005515 protein binding | IPI PMID:17110339 The architecture of the multisubunit TRAPP I complex suggest... | MARK AS OVER ANNOTATED | Summary: TRAPP-subunit interaction evidence is better represented as TRAPP complex membership than generic protein binding. Reason: Mark as over-annotated. Protein binding does not capture the specific TRAPPC4 role in TRAPP complex architecture or trafficking. Supporting Evidence: PMID:17110339 composed of seven subunits involved in ER-to-Golgi trafficking PMID:31794024 TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes |
| GO:0005515 protein binding | IPI PMID:21826244 TRAPPC4-ERK2 interaction activates ERK1/2, modulates its nuc... | MARK AS OVER ANNOTATED | Summary: TRAPPC4 binds ERK2 in CRC signaling assays, but generic protein binding is not an informative gene function. 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. Supporting Evidence: PMID:21826244 TRAPPC4 was found to bind with ERK2 |
| GO:0005795 Golgi stack | IEA GO_REF:0000107 | ACCEPT | Summary: Golgi stack localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: synaptic vesicle is more specific than the available synbindin localization evidence supports. 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. Supporting Evidence: PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side |
| GO:0016358 dendrite development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Dendrite development is broader and more causal than the synbindin evidence supports. Reason: Mark as over-annotated. The original neuronal paper discusses possible spine morphogenesis roles but explicitly leaves synbindin effector status unresolved. Supporting Evidence: PMID:11018053 the clustering of synbindin in spines requires syndecan-2 expression PMID:11018053 At present, we do not know whether synbindin acts as a downstream effector |
| GO:0030425 dendrite | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: dendrite reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. Reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. Supporting Evidence: PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: synapse reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. Reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. Supporting Evidence: PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites |
| GO:0048786 presynaptic active zone | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: presynaptic active zone is more specific than the available synbindin localization evidence supports. 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. Supporting Evidence: PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side |
| GO:0098839 postsynaptic density membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: postsynaptic density membrane is more specific than the available synbindin localization evidence supports. 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. Supporting Evidence: PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side |
| GO:0005737 cytoplasm | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | ACCEPT | Summary: cytoplasm localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | ACCEPT | Summary: TRAPPC4 is required for TRAPP-mediated ER-to-Golgi/Golgi trafficking. Reason: Accept as a core process. TRAPPC4-deficient patient fibroblasts have delayed VSVG trafficking through the Golgi that is rescued by wild-type TRAPPC4. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it |
| GO:0006901 vesicle coat assembly | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | MODIFY | Summary: vesicle coat assembly overstates TRAPPC4 as a coat-assembly factor. 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 replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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:0048208 COPII vesicle coat assembly | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | MODIFY | Summary: COPII vesicle coat assembly overstates TRAPPC4 as a coat-assembly factor. 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 replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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, which captures the supported TRAPPC4/TRAPP trafficking role without relying on an obsolete term or unresolved tethering evidence. 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:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:1990071 TRAPPII protein complex | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | ACCEPT | Summary: TRAPPC4 is part of TRAPPII protein complex through the shared TRAPP core. Reason: Accept as complex-context membership. TRAPPC4 is a core subunit required for TRAPP assembly/stability, and the core participates in TRAPPII/TRAPPIII holocomplexes. Supporting Evidence: PMID:31794024 This TRAPP core then interacts with a number of accessory proteins to form two distinct, yet related complexes called TRAPP II PMID:31794024 affects the assembly of the core TRAPP complex and likely affects assembly of TRAPP II and TRAPP III in yeast |
| GO:1990072 TRAPPIII protein complex | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | ACCEPT | Summary: TRAPPC4 is part of TRAPPIII protein complex through the shared TRAPP core. Reason: Accept as complex-context membership. TRAPPC4 is a core subunit required for TRAPP assembly/stability, and the core participates in TRAPPII/TRAPPIII holocomplexes. Supporting Evidence: PMID:31794024 This TRAPP core then interacts with a number of accessory proteins to form two distinct, yet related complexes called TRAPP II PMID:31794024 affects the assembly of the core TRAPP complex and likely affects assembly of TRAPP II and TRAPP III in yeast |
| GO:0000139 Golgi membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Golgi membrane localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: endoplasmic reticulum localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0031982 vesicle | ISS GO_REF:0000024 | ACCEPT | Summary: vesicle localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0045211 postsynaptic membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: postsynaptic membrane reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. Reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. Supporting Evidence: PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IMP PMID:31794024 Deficiencies in vesicular transport mediated by TRAPPC4 are ... | ACCEPT | Summary: TRAPPC4 is required for TRAPP-mediated ER-to-Golgi/Golgi trafficking. Reason: Accept as a core process. TRAPPC4-deficient patient fibroblasts have delayed VSVG trafficking through the Golgi that is rescued by wild-type TRAPPC4. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it |
| GO:0006914 autophagy | IMP PMID:31794024 Deficiencies in vesicular transport mediated by TRAPPC4 are ... | ACCEPT | Summary: TRAPPC4 loss causes autophagy defects in patient fibroblasts and a yeast Trs23 model. 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. Supporting Evidence: PMID:31794024 basal autophagy defect and a delay in autophagic flux PMID:31794024 affects the assembly of the core TRAPP complex and likely affects assembly of TRAPP II and TRAPP III in yeast PMID:27066478 the connection of the mammalian TRAPP III complex to autophagy is currently not clear |
| GO:0030008 TRAPP complex | IMP PMID:31794024 Deficiencies in vesicular transport mediated by TRAPPC4 are ... | ACCEPT | Summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. 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. Supporting Evidence: PMID:31794024 TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes PMID:31794024 defect in TRAPP complex assembly and/or stability PMID:21525244 the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b |
| GO:0030008 TRAPP complex | IDA PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol... | ACCEPT | Summary: TRAPPC4/synbindin is a core TRAPP-complex subunit. 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. Supporting Evidence: PMID:31794024 TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes PMID:31794024 defect in TRAPP complex assembly and/or stability PMID:21525244 the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5694409 | ACCEPT | Summary: cytosol localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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:0005829 cytosol | TAS Reactome:R-HSA-5694418 | ACCEPT | Summary: cytosol localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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:0005829 cytosol | TAS Reactome:R-HSA-5694439 | ACCEPT | Summary: cytosol localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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:0005829 cytosol | TAS Reactome:R-HSA-5694441 | ACCEPT | Summary: cytosol localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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:0005829 cytosol | TAS Reactome:R-HSA-8877475 | ACCEPT | Summary: cytosol localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: Reactome:R-HSA-5694409 The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic 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:0005795 Golgi stack | ISS PMID:11018053 Synbindin, A novel syndecan-2-binding protein in neuronal de... | ACCEPT | Summary: Golgi stack localization is consistent with TRAPPC4 as a cytosolic/peripheral TRAPP trafficking subunit. Reason: Accept as supported localization for TRAPPC4-containing TRAPP reactions and/or synbindin membrane-cistern/vesicle localization. Supporting Evidence: PMID:31794024 significantly delayed entry into and exit from the Golgi PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites Reactome:R-HSA-5694439 TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic |
| GO:0008021 synaptic vesicle | ISS PMID:11018053 Synbindin, A novel syndecan-2-binding protein in neuronal de... | MARK AS OVER ANNOTATED | Summary: synaptic vesicle is more specific than the available synbindin localization evidence supports. 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. Supporting Evidence: PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side |
| GO:0016358 dendrite development | ISS PMID:11018053 Synbindin, A novel syndecan-2-binding protein in neuronal de... | MARK AS OVER ANNOTATED | Summary: Dendrite development is broader and more causal than the synbindin evidence supports. Reason: Mark as over-annotated. The original neuronal paper discusses possible spine morphogenesis roles but explicitly leaves synbindin effector status unresolved. Supporting Evidence: PMID:11018053 the clustering of synbindin in spines requires syndecan-2 expression PMID:11018053 At present, we do not know whether synbindin acts as a downstream effector |
| GO:0030425 dendrite | ISS PMID:11018053 Synbindin, A novel syndecan-2-binding protein in neuronal de... | KEEP AS NON CORE | Summary: dendrite reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. Reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. Supporting Evidence: PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites |
| GO:0045202 synapse | ISS PMID:11018053 Synbindin, A novel syndecan-2-binding protein in neuronal de... | KEEP AS NON CORE | Summary: synapse reflects the neuronal synbindin context but is not core to TRAPPC4 PN function. Reason: Keep as non-core. The synbindin literature supports postsynaptic/dendritic localization, while the core gene-level function remains TRAPP complex trafficking/autophagy. Supporting Evidence: PMID:11018053 associated with synaptic membranes, mainly at the postsynaptic side PMID:11018053 present on membrane-bound cisterns and vesicles within the soma and dendrites |
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Download this section (compressed HTML)Q: Should TRAPPC4 receive a contributes_to annotation for TRAPP complex RAB1 guanine-nucleotide exchange activity based on direct subunit-essential evidence?
Suggested experts: GO transport editors, Reactome TRAPP curators
Q: Should TRAPPC4 autophagy be represented only by broad autophagy, or can the field support a more specific TRAPP/TRAPPIII-dependent autophagosome maturation term?
Suggested experts: GO autophagy editors, TRAPP/autophagy domain experts
Q: Should neuronal synbindin annotations be kept as non-core human TRAPPC4 annotations or limited to experimentally tested rodent orthologs?
Suggested experts: GO synapse editors, GO transport editors
Experiment: Reconstitute TRAPPC4-containing TRAPP core and TRAPPII/TRAPPIII complexes with TRAPPC4 depletion or interface mutants and measure RAB1 GDP-GTP exchange.
Hypothesis: TRAPPC4 is required as a core TRAPP subunit for complex-level RAB1 GEF activity and stable TRAPP holocomplex assembly.
Type: complex reconstitution and RAB1 GEF assay
Experiment: 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.
Hypothesis: TRAPPC4 deficiency disrupts ER-to-Golgi vesicle-mediated transport by destabilizing TRAPP complexes.
Type: cellular trafficking rescue assay
Experiment: 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.
Hypothesis: TRAPPC4 autophagy phenotypes are mediated through TRAPP complex assembly and TRAPPIII/RAB1 trafficking context.
Type: autophagy and trafficking separation assay
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