TRAPPC3

UniProt ID: O43617
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TRAPPC3 is the human Bet3 homolog and a core TRAPP-complex subunit. It contributes to complex-level RAB1 guanine-nucleotide exchange factor activity, TRAPP/TRAPPII/TRAPPIII complex architecture, and ER-to-Golgi vesicle-mediated transport. Autophagophore-recruitment effects are best understood through TRAPP complex membership and TRAPPIII/RAB1 context rather than independent TRAPPC3-specific autophagy activity.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005085 guanyl-nucleotide exchange factor activity
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC3 contributes to complex-level RAB1 guanine-nucleotide exchange factor activity as a TRAPP subunit.
Reason: Accept with the contributes_to qualifier. The TRAPPC complex, not isolated TRAPPC3, provides the GEF activity for RAB1/Ypt1-family GTPases.
Supporting Evidence:
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
PMID:21525244
the complex acts as a guanine nucleotide exchange factor (GEF) for Ypt1p
GO:0005829 cytosol
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC3-containing TRAPP complexes mediate ER-to-Golgi vesicle traffic through TRAPP/RAB1 biology.
Reason: Accept as a core process for TRAPPC3. Multiple human/mammalian TRAPP sources and Reactome support ER-to-Golgi trafficking.
Supporting Evidence:
PMID:18930054
The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi
PMID:21525244
C4orf41 and TTC-15 (which we call TRAPPC11 and TRAPPC12, respectively) in ER-to-Golgi trafficking at a very early stage
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:0006891 intra-Golgi vesicle-mediated transport
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Intra-Golgi transport is plausible through TRAPPII/Golgi trafficking context but is less central than ER-to-Golgi transport for human TRAPPC3.
Reason: Keep as non-core. The TRAPPII/Golgi evidence supports a context-specific trafficking role, while the core TRAPPC3 process remains ER-to-Golgi/TRAPP/RAB1 transport.
Supporting Evidence:
PMID:21453443
for distinct tethering events at Golgi membranes
PMID:18930054
different functions in the regulation of ER-to-Golgi traffic
GO:0030008 TRAPP complex
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC3/Bet3 is a core TRAPP complex subunit.
Reason: Accept as core cellular-component membership. This is the cleanest gene-level representation of the PN TRAPP component leaf.
Supporting Evidence:
PMID:16828797
crystal structure of a human Bet3-Tpc6B heterodimer, which represents a core sub-complex in the assembly of TRAPP
PMID:16828797
Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further TRAPP subunit
PMID:21525244
the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
GO:0033106 cis-Golgi network membrane
IBA
GO_REF:0000033 		ACCEPT
Summary: cis-Golgi network membrane is a supported active site for TRAPPC3-containing TRAPP complexes.
Reason: Accept as a supported active location for TRAPP/RAB1 ER-to-Golgi trafficking.
Supporting Evidence:
PMID:18930054
The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi
Reactome:R-HSA-5694439
TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000044 		ACCEPT
Summary: TRAPPC3 participates in ER-derived vesicle trafficking and is mapped to the endoplasmic reticulum.
Reason: Accept as a supported location for ER-to-Golgi trafficking.
Supporting Evidence:
PMID:18930054
The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi
Reactome:R-HSA-5694439
TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23
GO:0005794 Golgi apparatus
IEA
GO_REF:0000044 		ACCEPT
Summary: TRAPPC3 functions in TRAPP trafficking at Golgi/cis-Golgi membranes.
Reason: Accept as supported location for TRAPP-mediated ER-to-Golgi and Golgi trafficking.
Supporting Evidence:
PMID:18930054
The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi
PMID:21453443
for distinct tethering events at Golgi membranes
PMID:18930054
different functions in the regulation of ER-to-Golgi traffic
GO:0030008 TRAPP complex
IEA
GO_REF:0000120 		ACCEPT
Summary: TRAPPC3/Bet3 is a core TRAPP complex subunit.
Reason: Accept as core cellular-component membership. This is the cleanest gene-level representation of the PN TRAPP component leaf.
Supporting Evidence:
PMID:16828797
crystal structure of a human Bet3-Tpc6B heterodimer, which represents a core sub-complex in the assembly of TRAPP
PMID:16828797
Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further TRAPP subunit
PMID:21525244
the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
GO:0048193 Golgi vesicle transport
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: Golgi vesicle transport is a broad trafficking context supported by TRAPP/TRAPPII biology.
Reason: Keep as non-core because it is broader/less precise than ER-to-Golgi vesicle-mediated transport and intra-Golgi TRAPPII context.
Supporting Evidence:
PMID:21453443
for distinct tethering events at Golgi membranes
PMID:18930054
different functions in the regulation of ER-to-Golgi traffic
GO:0005515 protein binding
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:16828797
Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:16908848
Unique self-palmitoylation activity of the transport protein... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:18930054
Distinct isocomplexes of the TRAPP trafficking factor coexis... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:21453443
Organization and assembly of the TRAPPII complex. 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:21827752
A yeast two hybrid screen identifies SPATA4 as a TRAPP inter... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0000139 Golgi membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: Golgi membrane localization is consistent with TRAPPC3/Bet3 role in TRAPP trafficking complexes.
Reason: Accept as a more specific Golgi location for the TRAPP trafficking role.
Supporting Evidence:
PMID:21453443
for distinct tethering events at Golgi membranes
PMID:18930054
different functions in the regulation of ER-to-Golgi traffic
GO:0005829 cytosol
IEA
GO_REF:0000107 		ACCEPT
Summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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:0005737 cytoplasm
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC3-containing TRAPP complexes mediate ER-to-Golgi vesicle traffic through TRAPP/RAB1 biology.
Reason: Accept as a core process for TRAPPC3. Multiple human/mammalian TRAPP sources and Reactome support ER-to-Golgi trafficking.
Supporting Evidence:
PMID:18930054
The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi
PMID:21525244
C4orf41 and TTC-15 (which we call TRAPPC11 and TRAPPC12, respectively) in ER-to-Golgi trafficking at a very early stage
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: TRAPPC3 interacts with COPII/SEC23-associated ER-derived vesicle trafficking machinery, but it is not a vesicle coat assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport to capture the supported trafficking role without overclaiming coat assembly.
Supporting Evidence:
Reactome:R-HSA-5694439
TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23
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: The COPII evidence supports TRAPPC3-SEC23 recruitment to ER-derived vesicles, not direct COPII coat assembly by TRAPPC3.
Reason: Modify to ER-to-Golgi vesicle-mediated transport.
Supporting Evidence:
Reactome:R-HSA-5694439
TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23
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: This obsolete vesicle-tethering annotation should not be kept as-is, and direct mammalian TRAPP tethering evidence remains unresolved.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, the safer supported TRAPPC3 process.
Supporting Evidence:
PMID:27066478
evidence that any TRAPP complex acts as a membrane tether is currently inconclusive
PMID:21525244
Direct demonstration of mammalian TRAPP as a vesicle tether has yet to be shown
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: TRAPPC3 is represented in TRAPPII complex models and ComplexPortal annotations.
Reason: Accept as supported TRAPP subtype membership; process-level claims should remain tied to TRAPP/RAB1 trafficking.
Supporting Evidence:
PMID:21453443
for distinct tethering events at Golgi membranes
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:1990072 TRAPPIII protein complex
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC3 is represented in TRAPPIII complex models, which are relevant to the PN autophagy-recruitment context.
Reason: Accept as supported complex membership while keeping autophagy as context rather than assigning a broad autophagy BP.
Supporting Evidence:
Reactome:R-HSA-8877475
RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) and contribute to the localization of ATG9
PMID:27066478
the connection of the mammalian TRAPP III complex to autophagy is currently not clear
GO:0005515 protein binding
IPI
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC3.
Reason: Mark as over-annotated. Specific interaction biology should be represented as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context, not generic GO:0005515.
GO:0030008 TRAPP complex
IDA
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		ACCEPT
Summary: TRAPPC3/Bet3 is a core TRAPP complex subunit.
Reason: Accept as core cellular-component membership. This is the cleanest gene-level representation of the PN TRAPP component leaf.
Supporting Evidence:
PMID:16828797
crystal structure of a human Bet3-Tpc6B heterodimer, which represents a core sub-complex in the assembly of TRAPP
PMID:16828797
Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further TRAPP subunit
PMID:21525244
the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694409 		ACCEPT
Summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
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: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side of ER-Golgi trafficking membranes.
Reason: Accept as supported location for a peripheral trafficking-complex subunit.
Supporting Evidence:
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
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III

Core Functions

TRAPPC3 contributes the Bet3 core subunit to TRAPP complexes, supporting complex-level RAB1 guanine-nucleotide exchange and ER-to-Golgi trafficking. It should be modeled as contributing to the TRAPP complex activity rather than independently enabling GEF activity.

Directly Involved In:
endoplasmic reticulum to Golgi vesicle-mediated transport
Cellular Locations:
cytosol cytoplasm cis-Golgi network membrane Golgi membrane endoplasmic reticulum Golgi apparatus
In Complex:
TRAPP complex
Supporting Evidence:
  • PMID:16828797
    crystal structure of a human Bet3-Tpc6B heterodimer, which represents a core sub-complex in the assembly of TRAPP
  • PMID:16828797
    Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further TRAPP subunit
  • PMID:21525244
    the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
  • Reactome:R-HSA-5694409
    The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
  • Reactome:R-HSA-8877475
    RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
  • PMID:21525244
    the complex acts as a guanine nucleotide exchange factor (GEF) for Ypt1p
  • PMID:18930054
    The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi
  • PMID:21525244
    C4orf41 and TTC-15 (which we call TRAPPC11 and TRAPPC12, respectively) in ER-to-Golgi trafficking at a very early stage
  • Reactome:R-HSA-5694439
    TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
  • Reactome:R-HSA-5694439
    TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
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:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:16189514
Towards a proteome-scale map of the human protein-protein interaction network.
PMID:16828797
Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric complexes with Bet3 and Mum2.
PMID:16908848
Unique self-palmitoylation activity of the transport protein particle component Bet3: a mechanism required for protein stability.
PMID:18930054
Distinct isocomplexes of the TRAPP trafficking factor coexist inside human cells.
PMID:21453443
Organization and assembly of the TRAPPII complex.
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.
PMID:21827752
A yeast two hybrid screen identifies SPATA4 as a TRAPP interactor.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
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 TRAPPC3 and related TRAPP core subunits retain contributes_to RAB1 GEF annotations even when the complex-level catalytic subunit assignment is not fully resolved?

Suggested experts: GO transport editors, Reactome TRAPP curators

Q: Should TRAPPIII complex membership be considered sufficient for PN autophagophore-recruitment context without assigning broad autophagy process terms?

Suggested experts: GO autophagy editors, ComplexPortal curators

Q: Should TRAPPC3 coat-assembly annotations be replaced by ER-to-Golgi vesicle-mediated transport or by a more specific TRAPPC/COPII recruitment term if one exists?

Suggested experts: GO transport editors, ComplexPortal curators

Suggested Experiments

Experiment: Reconstitute TRAPPC3-containing TRAPP complexes and measure RAB1 GDP-GTP exchange with TRAPPC3 depletion/rescue or interface mutants.

Hypothesis: TRAPPC3 is required as a core TRAPP subunit for complex-level RAB1 GEF activity.

Type: complex reconstitution and RAB1 GEF assay

Experiment: Test TRAPPC3 mutants that disrupt TRAPPC6/TRAPPC1 interfaces for effects on ER-to-Golgi cargo trafficking, SEC23/COPII association, and Golgi membrane recruitment.

Hypothesis: TRAPPC3 scaffolding of core TRAPP interactions is required for ER-to-Golgi vesicle-mediated transport.

Type: trafficking rescue and complex-interface assay

Experiment: Separate TRAPPII and TRAPPIII pools in TRAPPC3 rescue cells and assay ATG9 localization plus canonical ER-to-Golgi transport in parallel.

Hypothesis: TRAPPC3 autophagy phenotypes depend on TRAPPIII/RAB1 context and should be distinguished from core ER-to-Golgi transport defects.

Type: TRAPP subtype-specific autophagy/traffic assay

📚 Additional Documentation

Notes

(TRAPPC3-notes.md)

TRAPPC3 notes

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

Falcon deep research was requested with just deep-research-falcon human TRAPPC3; the provider timed out after 600 seconds and no Falcon research file was generated.

TRAPPC3 is the human Bet3 homolog and a core TRAPP complex subunit. UniProt states that TRAPPC3 is a component of the multisubunit TRAPP complex and that TRAPPC6B-TRAPPC3 interacts with TRAPPC1, likely providing a core for TRAPP complex formation. The TRAPPC1/TRAPPC3/TRAPPC6B structural paper reports the "crystal structure of a human Bet3-Tpc6B heterodimer" as a "core sub-complex in the assembly of TRAPP" and says Bet3-Tpc6A/Bet3-Tpc6B can recruit Mum2/TRAPPC1 PMID:16828797. This supports TRAPP complex membership and specific TRAPP-subunit interactions; generic protein binding should still be treated as over-annotated.

TRAPPC3 has stronger direct support than TRAPPC1 for contributing to complex-level RAB1 GEF/transport functions. The seeded GOA includes GO:0005085 guanyl-nucleotide exchange factor activity with qualifier contributes_to, which is appropriate because TRAPPC3 is a subunit of the TRAPPC complex rather than an independent RAB1 GEF. 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 guanine-nucleotide exchange factor for RAB1 and is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC component TRAPPC3 and the coat protein SEC23" [Reactome:R-HSA-5694439 "COPII coat binds TRAPPCII and RAB1:GDP"]. This makes contributes_to GEF activity and ER-to-Golgi trafficking core.

The main process role is ER-to-Golgi vesicle-mediated transport, with some TRAPPII/intra-Golgi context. A human TRAPP isocomplex paper says "The transport protein particle (TRAPP) complex is required for proper vesicular transport from the ER to the Golgi" and describes human TRAPP isocomplexes that may regulate ER-to-Golgi traffic PMID:18930054. A mammalian TRAPP component paper states that "TRAPP is a multisubunit tethering complex implicated in multiple vesicle trafficking pathways" and identifies mammalian TRAPP components with roles "in ER-to-Golgi trafficking at a very early stage" PMID:21525244. A TRAPPII assembly abstract says TRAPPII is required "for distinct tethering events at Golgi membranes" PMID:21453443. ER-to-Golgi transport is core; intra-Golgi/Golgi vesicle transport is plausible but should be non-core or lower confidence unless the evidence specifically supports TRAPPII late Golgi activity in human cells.

The PN autophagy context should be curated as complex membership, not a broad autophagy BP. The PN mapping rationale says the TRAPP component leaf is autophagy-contextual but that shared gene-level semantics are captured by TRAPP complex membership [projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv]. Reactome says in macroautophagy "RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) and contribute to the localization of ATG9" [Reactome:R-HSA-8877475 "TRAPPC complexes exchange GTP for GDP on RAB1"], but the TRAPP review cautions that "the connection of the mammalian TRAPP III complex to autophagy is currently not clear" PMID:27066478. Do not add a broad autophagy process annotation for TRAPPC3 based only on the PN context.

The coat-assembly and obsolete tethering annotations need revision. Reactome supports TRAPPC3/SEC23 interaction and TRAPPCII recruitment to ER-derived vesicles, but not TRAPPC3 as a COPII coat-assembly factor. The TRAPP review says "evidence that any TRAPP complex acts as a membrane tether is currently inconclusive" PMID:27066478. Modify these rows to ER-to-Golgi vesicle-mediated transport rather than accepting coat assembly or obsolete vesicle tethering.

Annotation stance:
- Accept core: GO:0005085 with contributes_to; GO:0030008 TRAPP complex; GO:0006888 ER-to-Golgi vesicle-mediated transport; TRAPPII/TRAPPIII complex memberships; cytosol/cytoplasm, ER, Golgi/Golgi membrane/cis-Golgi network membrane.
- Keep as non-core: intra-Golgi vesicle-mediated transport and broad Golgi vesicle transport if supported by TRAPPII context but not central to the PN review.
- Modify: vesicle-mediated/coat/tethering rows that are broad, over-specific, or obsolete to ER-to-Golgi vesicle-mediated transport.
- Mark over-annotated: generic protein binding rows, even when the interaction partner is another TRAPP component; the specific biology should be captured as complex membership.

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 described the autophagophore-recruitment context as PN-specific and interpreted it through TRAPP complex membership and cautious TRAPPIII/RAB1 context rather than a broad autophagy process annotation.

Pn Notes

(TRAPPC3-pn-notes.md)

TRAPPC3 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O43617
  • 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: TRAPPC3 is the human Bet3 homolog and a core TRAPP-complex subunit. It contributes to complex-level RAB1 guanine-nucleotide exchange factor activity, TRAPP/TRAPPII/TRAPPIII complex architecture, and ER-to-Golgi vesicle-mediated transport. Autophagophore-recruitment effects are best understood through TRAPP complex membership and TRAPPIII/RAB1 context rather than independent TRAPPC3-specific autophagy activity.
  • Existing/core annotation action counts: ACCEPT: 20; KEEP_AS_NON_CORE: 2; MARK_AS_OVER_ANNOTATED: 13; MODIFY: 3

PN Consistency Summary

  • Consistency: Coherent. Notes, review, PN row ("TRAPP complex, core subunit"), and node mapping all agree TRAPPC3/Bet3 is a core TRAPP subunit contributing complex-level RAB1 GEF activity and ER-to-Golgi transport. Review carries GO:0030008 (IDA, IBA, IEA) plus contributes_to GO:0005085, consistent with PN. No contradictions; 13 generic protein-binding rows uniformly MARK_AS_OVER_ANNOTATED.
  • PN story / NEW pressure: PN Notes mention ATG9/ATG2 trafficking. Review keeps autophagy as TRAPPIII-membership context only (no autophagy BP), citing PMID:27066478 "connection ... not clear." Defensible — no gene-specific autophagy evidence for the core subunit. Conclusion: already captured via complex membership.
  • Evidence alignment: Strong overlap. PN titles ("Membrane Trafficking in Autophagy"; PMID:27066478) both present in review. Review adds substantial primary literature beyond the PN row (PMID:16828797 Bet3-Tpc6B structure, PMID:21525244, PMID:18930054, Reactome). No divergence/miscitation.
  • Verdict: Consistent; ACCEPT mapping. Cleanest gene-level representation of the PN TRAPP-component leaf; review is more richly evidenced than the PN row.

Full Consistency Review

  • UniProt: O43617 · 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. Notes, review, PN row ("TRAPP complex, core subunit"), and node mapping all agree TRAPPC3/Bet3 is a core TRAPP subunit contributing complex-level RAB1 GEF activity and ER-to-Golgi transport. Review carries GO:0030008 (IDA, IBA, IEA) plus contributes_to GO:0005085, consistent with PN. No contradictions; 13 generic protein-binding rows uniformly MARK_AS_OVER_ANNOTATED.
  • PN story / NEW pressure: PN Notes mention ATG9/ATG2 trafficking. Review keeps autophagy as TRAPPIII-membership context only (no autophagy BP), citing PMID:27066478 "connection ... not clear." Defensible — no gene-specific autophagy evidence for the core subunit. Conclusion: already captured via complex membership.
  • Mapping strategy: No change. GO:0030008 (OLS-verified) is already in GOA exactly; the projected term matches review. Scope correct.
  • Evidence alignment: Strong overlap. PN titles ("Membrane Trafficking in Autophagy"; PMID:27066478) both present in review. Review adds substantial primary literature beyond the PN row (PMID:16828797 Bet3-Tpc6B structure, PMID:21525244, PMID:18930054, Reactome). No divergence/miscitation.
  • Verdict: Consistent; ACCEPT mapping. Cleanest gene-level representation of the PN TRAPP-component leaf; review is more richly evidenced than the PN row.
  • Recommended edits: None required.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/TRAPPC3/TRAPPC3-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: O43617
  • 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: O43617
gene_symbol: TRAPPC3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TRAPPC3 is the human Bet3 homolog and a core TRAPP-complex subunit. It contributes to complex-level
  RAB1 guanine-nucleotide exchange factor activity, TRAPP/TRAPPII/TRAPPIII complex architecture, and
  ER-to-Golgi vesicle-mediated transport. Autophagophore-recruitment effects are best understood
  through TRAPP complex membership and TRAPPIII/RAB1 context rather than independent TRAPPC3-specific
  autophagy activity.
alternative_products:
- name: '1'
  id: O43617-1
- name: '2'
  id: O43617-2
  sequence_note: VSP_047015
existing_annotations:
- term:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: contributes_to
  review:
    summary: TRAPPC3 contributes to complex-level RAB1 guanine-nucleotide exchange
      factor activity as a TRAPP subunit.
    action: ACCEPT
    reason: Accept with the contributes_to qualifier. The TRAPPC complex, not isolated
      TRAPPC3, provides the GEF activity for RAB1/Ypt1-family GTPases.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-8877475
    - PMID:21525244
    supported_by:
    - &id001
      reference_id: Reactome:R-HSA-5694409
      supporting_text: The TRAPPC complex acts as a guanine-nucleotide exchange factor
        for RAB1, activating it
    - &id002
      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
    - &id014
      reference_id: PMID:21525244
      supporting_text: the complex acts as a guanine nucleotide exchange factor (GEF)
        for Ypt1p
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - &id003
      reference_id: Reactome:R-HSA-5694439
      supporting_text: TRAPPC is a multi-subunit tethering complex that facilitates
        ER-to-Golgi traffic
    - *id001
    - *id002
- 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: TRAPPC3-containing TRAPP complexes mediate ER-to-Golgi vesicle traffic
      through TRAPP/RAB1 biology.
    action: ACCEPT
    reason: Accept as a core process for TRAPPC3. Multiple human/mammalian TRAPP sources
      and Reactome support ER-to-Golgi trafficking.
    additional_reference_ids:
    - PMID:18930054
    - PMID:21525244
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - &id004
      reference_id: PMID:18930054
      supporting_text: The transport protein particle (TRAPP) complex is required for
        proper vesicular transport from the ER to the Golgi
    - &id011
      reference_id: PMID:21525244
      supporting_text: C4orf41 and TTC-15 (which we call TRAPPC11 and TRAPPC12,
        respectively) in ER-to-Golgi trafficking at a very early stage
    - *id003
    - *id001
- term:
    id: GO:0006891
    label: intra-Golgi vesicle-mediated transport
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Intra-Golgi transport is plausible through TRAPPII/Golgi trafficking
      context but is less central than ER-to-Golgi transport for human TRAPPC3.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. The TRAPPII/Golgi evidence supports a context-specific
      trafficking role, while the core TRAPPC3 process remains ER-to-Golgi/TRAPP/RAB1
      transport.
    additional_reference_ids:
    - PMID:21453443
    - PMID:18930054
    supported_by:
    - &id006
      reference_id: PMID:21453443
      supporting_text: for distinct tethering events at Golgi membranes
    - &id007
      reference_id: PMID:18930054
      supporting_text: different functions in the regulation of ER-to-Golgi traffic
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: TRAPPC3/Bet3 is a core TRAPP complex subunit.
    action: ACCEPT
    reason: Accept as core cellular-component membership. This is the cleanest
      gene-level representation of the PN TRAPP component leaf.
    additional_reference_ids:
    - PMID:16828797
    - PMID:21525244
    - PMID:27066478
    supported_by:
    - &id008
      reference_id: PMID:16828797
      supporting_text: crystal structure of a human Bet3-Tpc6B heterodimer, which
        represents a core sub-complex in the assembly of TRAPP
    - &id009
      reference_id: PMID:16828797
      supporting_text: Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further
        TRAPP subunit
    - &id010
      reference_id: PMID:21525244
      supporting_text: the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3,
        TRAPPC4, TRAPPC5, and TRAPPC6a/b
- term:
    id: GO:0033106
    label: cis-Golgi network membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: cis-Golgi network membrane is a supported active site for
      TRAPPC3-containing TRAPP complexes.
    action: ACCEPT
    reason: Accept as a supported active location for TRAPP/RAB1 ER-to-Golgi
      trafficking.
    additional_reference_ids:
    - Reactome:R-HSA-5694439
    - PMID:18930054
    supported_by:
    - *id004
    - &id005
      reference_id: Reactome:R-HSA-5694439
      supporting_text: TRAPPC is a guanine-nucleotide exchange factor for RAB1 and is
        recruited to ER-derived vesicles by virtue of an interaction between the TRAPPC
        component TRAPPC3 and the coat protein SEC23
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: TRAPPC3 participates in ER-derived vesicle trafficking and is mapped to the
      endoplasmic reticulum.
    action: ACCEPT
    reason: Accept as a supported location for ER-to-Golgi trafficking.
    additional_reference_ids:
    - PMID:18930054
    - Reactome:R-HSA-5694439
    supported_by:
    - *id004
    - *id005
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: TRAPPC3 functions in TRAPP trafficking at Golgi/cis-Golgi membranes.
    action: ACCEPT
    reason: Accept as supported location for TRAPP-mediated ER-to-Golgi and Golgi
      trafficking.
    additional_reference_ids:
    - PMID:18930054
    - PMID:21453443
    supported_by:
    - *id004
    - *id006
    - *id007
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: TRAPPC3/Bet3 is a core TRAPP complex subunit.
    action: ACCEPT
    reason: Accept as core cellular-component membership. This is the cleanest
      gene-level representation of the PN TRAPP component leaf.
    additional_reference_ids:
    - PMID:16828797
    - PMID:21525244
    - PMID:27066478
    supported_by:
    - *id008
    - *id009
    - *id010
- term:
    id: GO:0048193
    label: Golgi vesicle transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Golgi vesicle transport is a broad trafficking context supported by
      TRAPP/TRAPPII biology.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core because it is broader/less precise than ER-to-Golgi
      vesicle-mediated transport and intra-Golgi TRAPPII context.
    additional_reference_ids:
    - PMID:21453443
    - PMID:18930054
    supported_by:
    - *id006
    - *id007
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16828797
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16908848
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18930054
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21453443
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21827752
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0000139
    label: Golgi membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Golgi membrane localization is consistent with TRAPPC3/Bet3 role in TRAPP
      trafficking complexes.
    action: ACCEPT
    reason: Accept as a more specific Golgi location for the TRAPP trafficking role.
    additional_reference_ids:
    - PMID:21453443
    - PMID:18930054
    supported_by:
    - *id006
    - *id007
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: TRAPPC3-containing TRAPP complexes mediate ER-to-Golgi vesicle traffic
      through TRAPP/RAB1 biology.
    action: ACCEPT
    reason: Accept as a core process for TRAPPC3. Multiple human/mammalian TRAPP sources
      and Reactome support ER-to-Golgi trafficking.
    additional_reference_ids:
    - PMID:18930054
    - PMID:21525244
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id004
    - *id011
    - *id003
    - *id001
- term:
    id: GO:0006901
    label: vesicle coat assembly
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: TRAPPC3 interacts with COPII/SEC23-associated ER-derived vesicle
      trafficking machinery, but it is not a vesicle coat assembly factor.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport to capture the supported
      trafficking role without overclaiming coat assembly.
    proposed_replacement_terms:
    - &id012
      id: GO:0006888
      label: endoplasmic reticulum to Golgi vesicle-mediated transport
    additional_reference_ids:
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id005
    - &id013
      reference_id: Reactome:R-HSA-8877475
      supporting_text: TRAPPCII is recruited to ER-derived vesicles by virtue of an
        interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein
        SEC23
- term:
    id: GO:0048208
    label: COPII vesicle coat assembly
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The COPII evidence supports TRAPPC3-SEC23 recruitment to ER-derived
      vesicles, not direct COPII coat assembly by TRAPPC3.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport.
    proposed_replacement_terms:
    - *id012
    additional_reference_ids:
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id005
    - *id013
- term:
    id: GO:0099022
    label: obsolete vesicle tethering
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: This obsolete vesicle-tethering annotation should not be kept as-is, and
      direct mammalian TRAPP tethering evidence remains unresolved.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport, the safer supported
      TRAPPC3 process.
    proposed_replacement_terms:
    - *id012
    additional_reference_ids:
    - PMID:27066478
    - PMID:21525244
    - Reactome:R-HSA-5694439
    supported_by:
    - reference_id: PMID:27066478
      supporting_text: evidence that any TRAPP complex acts as a membrane tether is
        currently inconclusive
    - reference_id: PMID:21525244
      supporting_text: Direct demonstration of mammalian TRAPP as a vesicle tether has
        yet to be shown
    - *id003
- term:
    id: GO:1990071
    label: TRAPPII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC3 is represented in TRAPPII complex models and ComplexPortal
      annotations.
    action: ACCEPT
    reason: Accept as supported TRAPP subtype membership; process-level claims should
      remain tied to TRAPP/RAB1 trafficking.
    additional_reference_ids:
    - PMID:21453443
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - *id006
    - *id002
- term:
    id: GO:1990072
    label: TRAPPIII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC3 is represented in TRAPPIII complex models, which are relevant to
      the PN autophagy-recruitment context.
    action: ACCEPT
    reason: Accept as supported complex membership while keeping autophagy as context
      rather than assigning a broad autophagy BP.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 and the TRAPPCIII complex play a role in the formation of
        the pre-autophagosomal structure (PAS) and contribute to the localization of
        ATG9
    - reference_id: PMID:27066478
      supporting_text: the connection of the mammalian TRAPP III complex to autophagy is
        currently not clear
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21525244
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      as TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking context,
      not generic GO:0005515.
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IDA
  original_reference_id: PMID:21525244
  qualifier: part_of
  review:
    summary: TRAPPC3/Bet3 is a core TRAPP complex subunit.
    action: ACCEPT
    reason: Accept as core cellular-component membership. This is the cleanest
      gene-level representation of the PN TRAPP component leaf.
    additional_reference_ids:
    - PMID:16828797
    - PMID:21525244
    - PMID:27066478
    supported_by:
    - *id008
    - *id009
    - *id010
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694409
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694418
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694439
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694441
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8877475
  qualifier: located_in
  review:
    summary: TRAPPC3-containing TRAPP reactions occur on the cytosolic/cytoplasmic side
      of ER-Golgi trafficking membranes.
    action: ACCEPT
    reason: Accept as supported location for a peripheral trafficking-complex subunit.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id001
    - *id002
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:16828797
  title: 'Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric complexes
    with Bet3 and Mum2.'
  findings: []
- id: PMID:16908848
  title: 'Unique self-palmitoylation activity of the transport protein particle component
    Bet3: a mechanism required for protein stability.'
  findings: []
- id: PMID:18930054
  title: Distinct isocomplexes of the TRAPP trafficking factor coexist inside human
    cells.
  findings: []
- id: PMID:21453443
  title: Organization and assembly of the TRAPPII complex.
  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:21827752
  title: A yeast two hybrid screen identifies SPATA4 as a TRAPP interactor.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:27066478
  title: TRAPP Complexes in Secretion and Autophagy.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: Reactome:R-HSA-5694409
  title: Nucleotide exchange on RAB1
  findings: []
- id: Reactome:R-HSA-5694418
  title: RAB1:GTP binds USO1 and GORASP1:GOLGA2
  findings: []
- id: Reactome:R-HSA-5694439
  title: COPII coat binds TRAPPCII and RAB1:GDP
  findings: []
- id: Reactome:R-HSA-5694441
  title: CSNK1D phosphorylates SEC23
  findings: []
- id: Reactome:R-HSA-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: TRAPPC3 contributes the Bet3 core subunit to TRAPP complexes, supporting
    complex-level RAB1 guanine-nucleotide exchange and ER-to-Golgi trafficking. It
    should be modeled as contributing to the TRAPP complex activity rather than
    independently enabling GEF activity.
  directly_involved_in:
  - id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0033106
    label: cis-Golgi network membrane
  - id: GO:0000139
    label: Golgi membrane
  - id: GO:0005783
    label: endoplasmic reticulum
  - id: GO:0005794
    label: Golgi apparatus
  supported_by:
  - *id008
  - *id009
  - *id010
  - *id001
  - *id002
  - *id014
  - *id004
  - *id011
  - *id003
  - *id005
proposed_new_terms: []
suggested_questions:
- question: Should TRAPPC3 and related TRAPP core subunits retain contributes_to RAB1
    GEF annotations even when the complex-level catalytic subunit assignment is not
    fully resolved?
  experts:
  - GO transport editors
  - Reactome TRAPP curators
- question: Should TRAPPIII complex membership be considered sufficient for PN
    autophagophore-recruitment context without assigning broad autophagy process terms?
  experts:
  - GO autophagy editors
  - ComplexPortal curators
- question: Should TRAPPC3 coat-assembly annotations be replaced by ER-to-Golgi
    vesicle-mediated transport or by a more specific TRAPPC/COPII recruitment term if
    one exists?
  experts:
  - GO transport editors
  - ComplexPortal curators
suggested_experiments:
- description: Reconstitute TRAPPC3-containing TRAPP complexes and measure RAB1 GDP-GTP
    exchange with TRAPPC3 depletion/rescue or interface mutants.
  experiment_type: complex reconstitution and RAB1 GEF assay
  hypothesis: TRAPPC3 is required as a core TRAPP subunit for complex-level RAB1 GEF
    activity.
- description: Test TRAPPC3 mutants that disrupt TRAPPC6/TRAPPC1 interfaces for effects
    on ER-to-Golgi cargo trafficking, SEC23/COPII association, and Golgi membrane
    recruitment.
  experiment_type: trafficking rescue and complex-interface assay
  hypothesis: TRAPPC3 scaffolding of core TRAPP interactions is required for ER-to-Golgi
    vesicle-mediated transport.
- description: Separate TRAPPII and TRAPPIII pools in TRAPPC3 rescue cells and assay
    ATG9 localization plus canonical ER-to-Golgi transport in parallel.
  experiment_type: TRAPP subtype-specific autophagy/traffic assay
  hypothesis: TRAPPC3 autophagy phenotypes depend on TRAPPIII/RAB1 context and should be
    distinguished from core ER-to-Golgi transport defects.