TRAPPC4

UniProt ID: Q9Y296
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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.

Existing Annotations Review

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.
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.
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.
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.
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

Core Functions

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:
endoplasmic reticulum to Golgi vesicle-mediated transport autophagy
Cellular Locations:
cytosol cytoplasm endoplasmic reticulum Golgi membrane Golgi stack vesicle
In Complex:
TRAPP complex
Supporting Evidence:
  • PMID:31794024
    TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes
  • PMID:31794024
    one of the essential subunits for guanine nucleotide exchange factor activity for Rab1 GTPase
  • PMID:31794024
    defect in TRAPP complex assembly and/or stability
  • PMID:31794024
    significantly delayed entry into and exit from the Golgi
  • PMID:31794024
    basal autophagy defect and a delay in autophagic flux
  • 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

References

GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:11018053
Synbindin, A novel syndecan-2-binding protein in neuronal dendritic spines.
PMID:17110339
The architecture of the multisubunit TRAPP I complex suggests a model for vesicle tethering.
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.
PMID:21826244
TRAPPC4-ERK2 interaction activates ERK1/2, modulates its nuclear localization and regulates proliferation and apoptosis of colorectal cancer cells.
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
PMID:31794024
Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability.
Reactome:R-HSA-5694409
Nucleotide exchange on RAB1
Reactome:R-HSA-5694418
RAB1:GTP binds USO1 and GORASP1:GOLGA2
Reactome:R-HSA-5694439
COPII coat binds TRAPPCII and RAB1:GDP
Reactome:R-HSA-5694441
CSNK1D phosphorylates SEC23
Reactome:R-HSA-8877475
TRAPPC complexes exchange GTP for GDP on RAB1

Suggested Questions for Experts

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

Suggested Experiments

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

📚 Additional Documentation

Notes

(TRAPPC4-notes.md)

TRAPPC4 notes

Review started from just fetch-gene human TRAPPC4. The proteostasis network places TRAPPC4 under Autophagy-Lysosome Pathway > Autophagophore initiation and elongation > Autophagy component recruitment to autophagophore > TRAPP complex component, the same PN leaf as TRAPPC1 and TRAPPC3.

Falcon deep research was requested with just deep-research-falcon human TRAPPC4. The provider timed out after 600 seconds and no TRAPPC4-deep-research-falcon.md file was produced, so this review is completed from the accessible UniProt, GOA, cached literature, Reactome, and local PN-context evidence.

TRAPPC4/synbindin is a core TRAPP-complex subunit with direct human disease evidence. UniProt describes TRAPPC4 as a "Core component of the TRAPP complexes" and says it plays roles in ER-to-Golgi transport and autophagy. The direct TRAPPC4 paper states that "TRAPPC4, like its yeast Trs23 orthologue, is a core component of the TRAPP complexes" and "one of the essential subunits for guanine nucleotide exchange factor activity for Rab1 GTPase" PMID:31794024. It also reports that reduced TRAPPC4 caused a "defect in TRAPP complex assembly and/or stability" PMID:31794024. Therefore TRAPP complex membership, contribution to complex-level RAB1 GEF activity, and ER-Golgi transport are core.

The strongest process evidence is ER-to-Golgi/Golgi trafficking. Patient fibroblasts with reduced TRAPPC4 showed VSVG-GFP-ts045 "significantly delayed entry into and exit from the Golgi" and wild-type TRAPPC4 restored trafficking PMID:31794024. Reactome states that "The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it" [Reactome:R-HSA-5694409 "Nucleotide exchange on RAB1"] and that "TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic" [Reactome:R-HSA-5694439 "COPII coat binds TRAPPCII and RAB1:GDP"]. Broad vesicle-mediated transport, COPII coat assembly, and obsolete vesicle tethering rows should be modified to ER-to-Golgi vesicle-mediated transport rather than accepted as-is.

Unlike TRAPPC1 and TRAPPC3, TRAPPC4 has direct autophagy evidence in the seeded GOA. The TRAPPC4 disease paper reports a "basal autophagy defect and a delay in autophagic flux" in patient fibroblasts and yeast validation with "constitutive and stress-induced autophagic defects" PMID:31794024. Accept the existing broad autophagy annotation as supported, while noting that the mechanism is probably TRAPP complex assembly/stability and TRAPPIII/RAB1 context rather than a standalone autophagy-specific molecular activity.

TRAPPII/TRAPPIII complex annotations are supportable for TRAPPC4. The same paper says the human TRAPP core includes TRAPPC4 and forms TRAPP II and TRAPP III through accessory proteins; yeast data conclude that low Trs23 "affects the assembly of the core TRAPP complex and likely affects assembly of TRAPP II and TRAPP III" PMID:31794024. These are useful complex-context annotations for the PN TRAPP leaf.

The neuronal synbindin annotations should be kept as non-core or trimmed for over-specificity. The original synbindin paper reports that synbindin is "present on membrane-bound cisterns and vesicles within the soma and dendrites" and "associated with synaptic membranes, mainly at the postsynaptic side" PMID:11018053. This supports dendrite/synapse/postsynaptic membrane localization as a non-core neuronal context. However, synaptic vesicle, presynaptic active zone, postsynaptic density membrane, and broad dendrite development are likely over-specific because the paper itself says "At present, we do not know whether synbindin acts as a downstream effector" in spine formation PMID:11018053.

Generic protein binding is not useful as a TRAPPC4 function. The TRAPPI architecture paper and the ERK2 paper document specific interactions, including that "TRAPPC4 was found to bind with ERK2" PMID:21826244, but the generic GO term should be marked as over-annotated. Specific biology is better represented by TRAPP complex membership and, where relevant, a non-core MAPK signaling question.

Annotation stance:
- Core: TRAPP complex membership (GO:0030008), TRAPPII/TRAPPIII membership, contributes-to TRAPP complex RAB1 GEF activity, ER-to-Golgi vesicle-mediated transport, autophagy, cytoplasm/cytosol, ER, Golgi/Golgi membrane/Golgi stack, and broad vesicle localization.
- Non-core: neuronal synbindin localization at dendrites, synapse, and postsynaptic membrane.
- Modify: broad vesicle-mediated transport, vesicle coat assembly, COPII vesicle coat assembly, and obsolete vesicle tethering to ER-to-Golgi vesicle-mediated transport.
- Mark over-annotated: generic protein binding, synaptic vesicle, presynaptic active zone, postsynaptic density membrane, and broad dendrite development.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: the prior wording framed the TRAPP-component context as PN-specific and directly relevant because human patient fibroblasts and yeast Trs23 models show trafficking and autophagy defects.

Pn Notes

(TRAPPC4-pn-notes.md)

TRAPPC4 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y296
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • 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.
  • Existing/core annotation action counts: ACCEPT: 25; KEEP_AS_NON_CORE: 6; MARK_AS_OVER_ANNOTATED: 8; MODIFY: 4

PN Consistency Summary

  • Consistency: Coherent, with TRAPPC4 the strongest autophagy case among the core subunits. Notes, review, PN row ("TRAPP complex, core subunit"), and node mapping agree on core TRAPP membership + RAB1 GEF + ER-to-Golgi transport. Review additionally ACCEPTs GO:0006914 autophagy (IMP, PMID:31794024 patient fibroblasts + yeast Trs23). Neuronal synbindin annotations sensibly split KEEP_AS_NON_CORE (dendrite/synapse) vs MARK_AS_OVER_ANNOTATED (synaptic vesicle, active zone). No contradictions.
  • PN story / NEW pressure: Unlike the other subunits, TRAPPC4 has gene-specific autophagy evidence (PMID:31794024 "basal autophagy defect and a delay in autophagic flux"), so the existing GO:0006914 autophagy already captures the PN autophagophore-recruitment story. The PN node deliberately does NOT project autophagy (component-bucket scope); the gene's own GOA already carries it. Conclusion: already captured; no NEW term needed.
  • Evidence alignment: PN titles ("Membrane Trafficking in Autophagy"; PMID:27066478) both in review. Review adds the disease paper PMID:31794024 (load-bearing for autophagy + RAB1-GEF-essential claims) and the synbindin paper PMID:11018053 — beyond the PN row. No miscitation.
  • Verdict: Consistent; ACCEPT mapping. Best-evidenced TRAPP subunit; autophagy correctly retained at gene level, not over-projected from the PN bucket.

Full Consistency Review

  • UniProt: Q9Y296 · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component ; PN-node mapping: type-leaf mapped, scope=ok_for_propagation_to_go, GO:0030008 TRAPP complex (already_in_goa_exact)
  • Consistency: Coherent, with TRAPPC4 the strongest autophagy case among the core subunits. Notes, review, PN row ("TRAPP complex, core subunit"), and node mapping agree on core TRAPP membership + RAB1 GEF + ER-to-Golgi transport. Review additionally ACCEPTs GO:0006914 autophagy (IMP, PMID:31794024 patient fibroblasts + yeast Trs23). Neuronal synbindin annotations sensibly split KEEP_AS_NON_CORE (dendrite/synapse) vs MARK_AS_OVER_ANNOTATED (synaptic vesicle, active zone). No contradictions.
  • PN story / NEW pressure: Unlike the other subunits, TRAPPC4 has gene-specific autophagy evidence (PMID:31794024 "basal autophagy defect and a delay in autophagic flux"), so the existing GO:0006914 autophagy already captures the PN autophagophore-recruitment story. The PN node deliberately does NOT project autophagy (component-bucket scope); the gene's own GOA already carries it. Conclusion: already captured; no NEW term needed.
  • Mapping strategy: No change. Projected GO:0030008 (OLS-verified) is in GOA exactly. PN-node scope (component only) is appropriately narrower than the gene's autophagy annotation — correctly avoids over-projecting autophagy from the bucket.
  • Evidence alignment: PN titles ("Membrane Trafficking in Autophagy"; PMID:27066478) both in review. Review adds the disease paper PMID:31794024 (load-bearing for autophagy + RAB1-GEF-essential claims) and the synbindin paper PMID:11018053 — beyond the PN row. No miscitation.
  • Verdict: Consistent; ACCEPT mapping. Best-evidenced TRAPP subunit; autophagy correctly retained at gene level, not over-projected from the PN bucket.
  • Recommended edits: None required.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/TRAPPC4/TRAPPC4-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Autophagy component recruitment to autophagophore | TRAPP complex component

  • UniProt: Q9Y296
  • In branches: ALP
  • Notes: TRAPP complex, core subunit. The TRAPP complex serves as a GEF for RAB1. Involved in ATG9 and ATG2 trafficking
  • PN references (titles):
    • Membrane Trafficking in Autophagy - ScienceDirect
    • Frontiers | TRAPP Complexes in Secretion and Autophagy | Cell and Developmental Biology (frontiersin.org)
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0030008 TRAPP complex]
      rationale: This PN leaf is a curated component bucket for TRAPP subunits used in autophagophore recruitment. The matching GO cellular-component term is TRAPP complex, and the member genes already converge strongly on that assignment in existing GOA.
    • [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
    • [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0030008 TRAPP complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
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.