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.
