TRAPPC1

UniProt ID: Q9Y5R8
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TRAPPC1 is a small core subunit of the transport protein particle (TRAPP) complex. It contributes to TRAPP complex architecture and complex-level RAB1 guanine-nucleotide exchange/vesicle-trafficking functions, especially ER-to-Golgi vesicle-mediated transport. Autophagy component recruitment is best understood through TRAPP/TRAPPII/TRAPPIII complex membership rather than independent TRAPPC1 activity.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0030008 TRAPP complex
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC1 is a core subunit of the TRAPP complex, and this cellular-component annotation captures the strongest gene-level function.
Reason: Accept as core. Direct structural and review evidence place TRAPPC1/Mum2 in the conserved TRAPP core, and the PN mapping also resolves the autophagy-contextual leaf to TRAPP complex membership.
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:27066478
TRAPP is a highly conserved modular multi-subunit protein complex
PMID:27066478
Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC1 contributes to TRAPP-mediated ER-to-Golgi vesicle-mediated transport.
Reason: Accept as a core process. TRAPPC complexes activate RAB1 and facilitate ER-to-Golgi traffic, and TRAPPC1 is a core TRAPP subunit.
Supporting Evidence:
PMID:27066478
Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport
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
IEA
GO_REF:0000117 		ACCEPT
Summary: TRAPPC1 is a cytoplasmic/cytosolic TRAPP subunit associated with membrane-trafficking complexes.
Reason: Accept as a broad supported cellular location for a peripheral trafficking-complex subunit.
Supporting Evidence:
PMID:27066478
TRAPP is a highly conserved modular multi-subunit protein complex
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000044 		ACCEPT
Summary: TRAPPC1 participates in ER-derived vesicle trafficking and UniProt maps it to the endoplasmic reticulum.
Reason: Accept as a supported location for the ER-to-Golgi trafficking context.
Supporting Evidence:
PMID:27066478
Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport
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
GO:0005794 Golgi apparatus
IEA
GO_REF:0000044 		ACCEPT
Summary: TRAPPC1 participates in ER-to-Golgi transport and is associated with Golgi/cis-Golgi TRAPP trafficking functions.
Reason: Accept as a supported Golgi-location annotation for TRAPP-mediated ER-to-Golgi trafficking. Falcon deep research corroborates Golgi/ER-Golgi-interface localization for TRAPPC1 as part of TRAPP complexes (with cis-Golgi labeling reported for TRAPP-specific subunits in Drosophila).
Supporting Evidence:
PMID:27066478
Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
TRAPPC1, as part of TRAPP complexes, localizes primarily to the Golgi apparatus and the endoplasmic reticulum (ER)-Golgi interface
GO:0016192 vesicle-mediated transport
IEA
GO_REF:0000002 		MODIFY
Summary: Vesicle-mediated transport is true but too broad for TRAPPC1; the evidence supports the ER-to-Golgi/TRAPP/RAB1 pathway more specifically.
Reason: Modify to the more specific ER-to-Golgi vesicle-mediated transport term.
Supporting Evidence:
PMID:27066478
Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport
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:0030008 TRAPP complex
IEA
GO_REF:0000120 		ACCEPT
Summary: TRAPPC1 is a core subunit of the TRAPP complex, and this cellular-component annotation captures the strongest gene-level function.
Reason: Accept as core. Direct structural and review evidence place TRAPPC1/Mum2 in the conserved TRAPP core, and the PN mapping also resolves the autophagy-contextual leaf to TRAPP complex membership.
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:27066478
TRAPP is a highly conserved modular multi-subunit protein complex
PMID:27066478
Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1
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 TRAPPC1.
Reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than 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 TRAPPC1.
Reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than 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 TRAPPC1.
Reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than 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 TRAPPC1.
Reason: Mark as over-annotated. Specific interaction biology should be represented by TRAPP/TRAPPII/TRAPPIII complex membership rather than GO:0005515.
GO:0005737 cytoplasm
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC1 is a cytoplasmic/cytosolic TRAPP subunit associated with membrane-trafficking complexes.
Reason: Accept as a broad supported cellular location for a peripheral trafficking-complex subunit.
Supporting Evidence:
PMID:27066478
TRAPP is a highly conserved modular multi-subunit protein complex
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC1 contributes to TRAPP-mediated ER-to-Golgi vesicle-mediated transport.
Reason: Accept as a core process. TRAPPC complexes activate RAB1 and facilitate ER-to-Golgi traffic, and TRAPPC1 is a core TRAPP subunit.
Supporting Evidence:
PMID:27066478
Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport
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
file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
TRAPPIII activates Rab1 to regulate transport of newly synthesized proteins from the ER to the Golgi apparatus
GO:0006901 vesicle coat assembly
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		MODIFY
Summary: TRAPPC complexes interact with vesicle coats and RAB1 on ER-derived vesicles, but TRAPPC1 is not a coat-assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. The coat-related evidence supports recruitment/traffic context rather than direct vesicle 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 places TRAPPCII near SEC23/COPII vesicles, but does not show TRAPPC1 assembling the COPII coat.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, which captures the supported TRAPP/COPII/RAB1 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:0099022 obsolete vesicle tethering
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		MODIFY
Summary: This annotation uses an obsolete vesicle-tethering term, and the cited TRAPP review cautions that direct TRAPP tethering evidence is inconclusive.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, the safer supported process for TRAPPC1/TRAPP complex function.
Supporting Evidence:
PMID:27066478
evidence that any TRAPP complex acts as a membrane tether is currently inconclusive
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: TRAPPC1 is represented in human TRAPPII complex models and ComplexPortal annotations.
Reason: Accept as a supported TRAPP complex subtype membership, while recognizing that gene-level process conclusions should remain centered on ER-Golgi transport and TRAPP/RAB1 function.
Supporting Evidence:
PMID:27066478
TRAPP is a highly conserved modular multi-subunit protein complex
PMID:27066478
Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
Reactome:R-HSA-8877475
Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind
GO:1990072 TRAPPIII protein complex
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC1 is represented in human TRAPPIII complex models; this is the TRAPP subtype most relevant to the PN autophagy recruitment context.
Reason: Accept as supported complex membership. The autophagy implication should be treated as context for TRAPPIII/RAB1 biology, not as a broad autophagy BP annotation for TRAPPC1. Falcon deep research likewise links autophagosome formation to the TRAPPIII holo-complex rather than to TRAPPC1 specifically.
Supporting Evidence:
PMID:27066478
TRAPP is a highly conserved modular multi-subunit protein complex
PMID:27066478
Core TRAPP contains four small subunits that self assemble to a stable complex, which has a GEF activity on Ypt1
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
file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
TRAPPIII has been localized to autophagy-related membranes where it participates in autophagosome formation
GO:0005576 extracellular region
TAS
Reactome:R-HSA-6798751 		MARK AS OVER ANNOTATED
Summary: The extracellular-region annotation comes from a broad Reactome neutrophil-degranulation event and is not supported as a core TRAPPC1 localization.
Reason: Mark as over-annotated. TRAPPC1 is a TRAPP trafficking-complex subunit associated with cytosol/ER/Golgi contexts, not a secreted extracellular protein.
Supporting Evidence:
Reactome:R-HSA-6798751
Azurophil or primary granules were originally defined by their high content of myeloperoxidase
GO:0035578 azurophil granule lumen
TAS
Reactome:R-HSA-6798751 		MARK AS OVER ANNOTATED
Summary: The azurophil-granule-lumen annotation is inherited from a broad Reactome degranulation context and lacks TRAPPC1-specific support.
Reason: Mark as over-annotated. It does not fit the core TRAPPC1/TRAPP complex localization or trafficking function.
Supporting Evidence:
Reactome:R-HSA-6798751
Azurophil or primary granules were originally defined by their high content of myeloperoxidase
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694409 		ACCEPT
Summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions.
Reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
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
Reactome:R-HSA-8877475
Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694418 		ACCEPT
Summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions.
Reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
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
Reactome:R-HSA-8877475
Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694439 		ACCEPT
Summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions.
Reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
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
Reactome:R-HSA-8877475
Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694441 		ACCEPT
Summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions.
Reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
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
Reactome:R-HSA-8877475
Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind
GO:0005829 cytosol
TAS
Reactome:R-HSA-8877475 		ACCEPT
Summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic face of ER-Golgi trafficking reactions.
Reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
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
Reactome:R-HSA-8877475
Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP, allowing GTP to bind

Core Functions

TRAPPC1 contributes a small core subunit to TRAPP complexes, supporting complex-level RAB1 guanine-nucleotide exchange and ER-to-Golgi trafficking. Its role is best represented as contribution to the TRAPP complex activity rather than an independent catalytic activity.

Directly Involved In:
endoplasmic reticulum to Golgi vesicle-mediated transport
Cellular Locations:
cytosol cytoplasm 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:27066478
    Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi transport
  • 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

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:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
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-6798751
Exocytosis of azurophil granule lumen proteins
Reactome:R-HSA-8877475
TRAPPC complexes exchange GTP for GDP on RAB1
PMID:16828797
Structure of the Bet3-Tpc6B core of TRAPP: two Tpc6 paralogs form trimeric complexes with Bet3 and Mum2.
file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
Falcon deep research report for TRAPPC1

Suggested Questions for Experts

Q: Should TRAPPC1 and other shared TRAPP subunits receive contributes_to annotations for TRAPPC complex RAB1 guanine-nucleotide exchange activity?

Suggested experts: GO transport editors, Reactome TRAPP curators

Q: Should TRAPP subunit PN autophagy contexts be captured only as TRAPPIII complex membership unless direct human autophagophore/PAS evidence is available?

Suggested experts: GO autophagy editors, GO cellular-component editors

Q: Should current TRAPPC1 vesicle coat assembly and obsolete vesicle tethering annotations be replaced by ER-to-Golgi vesicle-mediated transport or more specific TRAPP/RAB1 terms?

Suggested experts: ComplexPortal curators, GO transport editors

Suggested Experiments

Experiment: Reconstitute human TRAPPII/TRAPPIII complexes with and without TRAPPC1 and measure RAB1 GDP-GTP exchange activity.

Hypothesis: TRAPPC1 is required as a core scaffold subunit for TRAPPC complex-level RAB1 GEF activity rather than acting as an independent catalytic subunit.

Type: complex reconstitution and RAB1 GEF assay

Experiment: Use TRAPPC1 knockout and rescue cells to assay ER-to-Golgi cargo transport, COPII-vesicle association, and Golgi localization of TRAPP components.

Hypothesis: TRAPPC1 loss disrupts TRAPP-dependent ER-to-Golgi vesicle-mediated transport by destabilizing or mislocalizing TRAPP complexes.

Type: cellular trafficking rescue assay

Experiment: Measure ATG9 localization and autophagophore initiation markers in TRAPPC1 rescue cells while separately monitoring ER-to-Golgi trafficking defects.

Hypothesis: Any TRAPPC1 autophagy phenotype is mediated through TRAPPIII/RAB1 trafficking context and should not be generalized to a broad autophagy core function without direct evidence.

Type: autophagy-context separation assay

Deep Research

Falcon

(TRAPPC1-deep-research-falcon.md)
Comprehensive Research Report: TRAPPC1 (Trafficking Protein Particle Complex Subunit 1) Falcon Edison Scientific Literature 27 citations 1 artifacts 2026-06-20T06:05:41.909102
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Comprehensive Research Report: TRAPPC1 (Trafficking Protein Particle Complex Subunit 1)

Gene Identity and Verification

TRAPPC1 (UniProt accession Q9Y5R8) encodes the trafficking protein particle complex subunit 1 in humans, also known as BET5 homolog or MUM2 (multiple myeloma protein 2) (hall2024trappopathiesseveremultisystem pages 1-2, zykaj2024ahumanizedyeast pages 1-2). This protein is the human ortholog of yeast Bet5 and belongs to the TRAPP small subunits family, specifically the BET5 subfamily, confirming alignment with the UniProt annotation provided (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 3-5). TRAPPC1 is highly conserved across eukaryotes, from yeast to mammals, reflecting its essential role in fundamental cellular processes (bagde2023thetrappcomplexes pages 1-3, hall2024trappopathiesseveremultisystem pages 1-2).

Primary Molecular Function and Structure

Core Catalytic Role in Rab GTPase Activation

TRAPPC1 functions as a critical structural and catalytic component of the TRAPP (TRAnsport Protein Particle) complexes, which act as guanine nucleotide exchange factors (GEFs) for Rab GTPases (galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 1-2). The TRAPP complexes are multisubunit tethering factors that regulate membrane trafficking in eukaryotic cells by catalyzing the exchange of GDP for GTP on specific Rab GTPases, thereby activating these molecular switches (lipatova2019yptrabgtpasesand pages 1-3).

Crystallographic studies have revealed that TRAPPC1, together with TRAPPC3 (Bet3) and TRAPPC4 (Trs23), forms the canonical Rab-binding interface and catalytic site of the TRAPP core (lamber2019rabregulationby pages 1-2, galindo2023thetrappcomplexes pages 7-9). The region of interaction between the TRAPP core and Rab GTPases (such as yeast Ypt1/Rab1) is primarily formed by TRAPPC4, with smaller contributions from TRAPPC3 and TRAPPC1 (galindo2023thetrappcomplexes pages 7-9). TRAPPC5 also participates in GEF activity by functioning allosterically, affecting the conformation of TRAPPC4 and accelerating GDP dissociation from Rab GTPases more than 400-fold (galindo2023thetrappcomplexes pages 5-7, galindo2023thetrappcomplexes pages 7-9).

TRAPP Complex Architecture

TRAPPC1 is a core subunit shared by two major TRAPP complexes in metazoans: TRAPPII and TRAPPIII (galindo2023thetrappcomplexes pages 1-2, riedel2018thetwotrapp pages 1-2). Both complexes share a common core of seven small subunits: TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3 (present in two copies), TRAPPC4, TRAPPC5, and TRAPPC6A/B (jenkins2020thesubstratespecificity pages 1-2, galindo2023thetrappcomplexes pages 3-5). This octameric core forms the structural platform for Rab activation and exhibits two-fold rotational symmetry (galindo2023thetrappcomplexes pages 3-5).

The TRAPPC1 and TRAPPC4 subunits form the center of the TRAPP core, with similar three-dimensional folds despite structural differences (galindo2023thetrappcomplexes pages 1-2). Recent cryo-electron microscopy (cryo-EM) structures from both yeast and Drosophila have unveiled the complete architecture of TRAPP complexes, showing how TRAPPC1 integrates into the core structure (galindo2023thetrappcomplexes pages 1-2, harris2021biochemicalinsightinto pages 1-5, riedel2018thetwotrapp pages 2-4).

Substrate Specificity and GEF Activity

Differential Rab Activation by TRAPPII and TRAPPIII

While TRAPPC1 itself does not determine substrate specificity, it is essential for the GEF activity of both TRAPPII and TRAPPIII complexes (bagde2023thetrappcomplexes pages 1-3, galindo2023thetrappcomplexes pages 7-9). The two TRAPP complexes use the same catalytic site containing TRAPPC1 but achieve Rab specificity through their complex-specific large subunits:

TRAPPII Complex: Contains the core subunits including TRAPPC1 plus two specific large subunits, TRAPPC9 (Trs120) and TRAPPC10 (Trs130) (jenkins2020thesubstratespecificity pages 1-2, galindo2023thetrappcomplexes pages 3-5). TRAPPII primarily activates Rab11, which regulates endocytic recycling, exocytosis, and membrane delivery during cytokinesis and ciliogenesis (galindo2023thetrappcomplexes pages 1-2). Biochemical studies have shown that human TRAPPII also has GEF activity toward Rab43 and Rab19, both Golgi-localized GTPases (jenkins2020thesubstratespecificity pages 3-5, harris2021biochemicalinsightinto pages 1-5).

TRAPPIII Complex: Contains the core subunits including TRAPPC1 plus four specific subunits: TRAPPC8, TRAPPC11, TRAPPC12, and TRAPPC13 (riedel2018thetwotrapp pages 1-2, harris2021biochemicalinsightinto pages 1-5). TRAPPIII activates Rab1, a master regulator of the early secretory pathway and autophagy (galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 1-2). TRAPPIII has been shown to have GEF activity specifically against Rab1 and Rab43, with no detectable activity against 18 other Rab GTPases tested (harris2021biochemicalinsightinto pages 1-5).

Both TRAPPII and TRAPPIII complexes show enhanced GEF activity when the Rab GTPase is presented on lipid membranes, with activity increasing on negatively charged membrane surfaces (jenkins2020thesubstratespecificity pages 3-5, harris2021biochemicalinsightinto pages 1-5).

Subcellular Localization

TRAPPC1, as part of TRAPP complexes, localizes primarily to the Golgi apparatus and the endoplasmic reticulum (ER)-Golgi interface (riedel2018thetwotrapp pages 2-4, hall2024trappopathiesseveremultisystem pages 1-2). Immunofluorescence studies in Drosophila cultured cells showed that TRAPPIII-specific subunits are Golgi-localized with extensive colocalization with the cis-Golgi marker GM130, indicating a location toward the cis end of the Golgi stack (riedel2018thetwotrapp pages 2-4). TRAPPII-specific subunits also showed Golgi labeling close to cis-Golgi markers (riedel2018thetwotrapp pages 2-4).

Additionally, TRAPPIII has been localized to autophagy-related membranes where it participates in autophagosome formation (hall2024trappopathiesseveremultisystem pages 1-2, lipatova2019yptrabgtpasesand pages 1-3). The specific membrane recruitment of TRAPP complexes is mediated by amphipathic helices in complex-specific subunits and interactions with membrane phosphoinositides (galindo2023thetrappcomplexes pages 7-9).

Cellular Pathways and Biological Processes

Vesicular Transport Pathways

TRAPPC1-containing TRAPP complexes participate in multiple essential membrane trafficking pathways:

  1. ER-to-Golgi Transport: TRAPPIII activates Rab1 to regulate transport of newly synthesized proteins from the ER to the Golgi apparatus (hall2024trappopathiesseveremultisystem pages 1-2, lipatova2019yptrabgtpasesand pages 1-3). TRAPPC1 is essential for this early secretory pathway step, which is fundamental for cell viability.

  2. Intra-Golgi Trafficking: Both Rab1 (via TRAPPIII) and Rab11 (via TRAPPII) regulate trafficking through the Golgi, with evidence suggesting roles in cisternal progression and maturation (lipatova2019yptrabgtpasesand pages 1-3).

  3. Golgi-to-Plasma Membrane Transport: TRAPPII activates Rab11 to regulate post-Golgi secretion and exocytosis, including polarized transport to the growing bud in yeast and membrane delivery during cell division (galindo2023thetrappcomplexes pages 1-2, lipatova2019yptrabgtpasesand pages 1-3).

  4. Endocytic Recycling: Rab11 activated by TRAPPII regulates recycling endosome function and the return of internalized receptors to the plasma membrane (galindo2023thetrappcomplexes pages 1-2).

Autophagy

TRAPPC1 plays a critical role in autophagy through the TRAPPIII complex (hall2024trappopathiesseveremultisystem pages 1-2, lipatova2019yptrabgtpasesand pages 1-3). TRAPPIII activates Rab1 at the first step of macroautophagy, a cellular recycling pathway essential for maintaining cellular homeostasis. Studies in patient fibroblasts with TRAPPC1 variants showed basal autophagy defects and delayed autophagic flux, possibly due to unsealed autophagosomes, highlighting the importance of TRAPPC1 in autophagy regulation (bergen2020deficienciesinvesicular pages 1-2).

Coordination with Other Trafficking Machinery

TRAPP complexes work in concert with other membrane trafficking components. They interact with COPII coat proteins involved in ER-to-Golgi vesicle formation and were originally proposed to function as vesicle tethers (sacher2019trappopathiesanemerging pages 1-6, riedel2018thetwotrapp pages 2-4). The GEF activity of TRAPP toward Rab GTPases positions these complexes as key coordinators that link vesicle formation, transport, and fusion events.

Molecular Mechanism of GEF Activity

The mechanism by which TRAPPC1 contributes to Rab activation involves conformational changes in the TRAPP core. The C-terminus of TRAPPC3 (Bet3) sterically clashes with the switch I region of Rab GTPases when the Rab is in the nucleotide-bound form, favoring opening of the nucleotide-binding pocket and transition to the nucleotide-free state (galindo2023thetrappcomplexes pages 7-9). This allows GTP to bind and activate the Rab.

Comparison of the TRAPP core structure with and without bound Rab shows significant conformational changes at the three-way interface between TRAPPC4, TRAPPC5, and TRAPPC3, indicating that Rab binding depends on conformational changes in this interface (galindo2023thetrappcomplexes pages 7-9). TRAPPC1 participates in stabilizing this catalytic platform alongside TRAPPC4 and TRAPPC3.

Essentiality and Disease Associations

Essential for Cell Viability

TRAPPC1 is essential for cell viability in humans (galindo2023thetrappcomplexes pages 3-5, harris2021biochemicalinsightinto pages 1-5). This essentiality reflects its central role in maintaining functional TRAPP complexes required for fundamental cellular processes including secretion and autophagy. The core TRAPP subunits, including TRAPPC1, are required for the GEF activity of both TRAPPII and TRAPPIII complexes, and loss of core subunits disrupts TRAPP complex assembly and stability (bergen2020deficienciesinvesicular pages 1-2).

TRAPPopathies: TRAPPC1-Associated Neurodevelopmental Syndrome

Pathogenic variants in TRAPPC1 have been associated with severe neurodevelopmental disorders, contributing to a group of conditions collectively termed "TRAPPopathies" (hall2024trappopathiesseveremultisystem pages 1-2, sacher2019trappopathiesanemerging pages 1-6, zykaj2024ahumanizedyeast pages 1-2). The first reported individual with an autosomal recessive disorder caused by biallelic TRAPPC1 variants presented with severe neurodevelopmental disorder and myopathy (zykaj2024ahumanizedyeast pages 1-2).

Functional studies using patient-derived fibroblasts and humanized yeast models demonstrated that TRAPPC1 variants led to:
- Reduced TRAPPC1 protein levels while other TRAPP subunits remained unaffected
- Defects in TRAPP complex assembly and/or stability
- Significantly delayed intracellular trafficking through the Golgi (both entry and exit)
- Basal autophagy defects and delayed autophagic flux
- Altered Golgi morphology

Importantly, lentiviral expression of wild-type TRAPPC1 in patient fibroblasts restored normal trafficking, confirming that the trafficking defects were specifically due to reduced TRAPPC1 levels (bergen2020deficienciesinvesicular pages 1-2, zykaj2024ahumanizedyeast pages 1-2).

TRAPPopathies caused by variants in different TRAPP subunits present with diverse but partially overlapping phenotypes, commonly affecting neurological, skeletal, and muscular systems (hall2024trappopathiesseveremultisystem pages 1-2, sacher2019trappopathiesanemerging pages 1-6). This contrasts with other tethering factor deficiencies where variants in different subunits result in identical phenotypes, suggesting that some TRAPP proteins may have complex-independent functions or that different TRAPP complexes have distinct tissue-specific roles.

Recent Developments (2023-2024)

Recent authoritative reviews have synthesized current understanding of TRAPP complex function (galindo2023thetrappcomplexes pages 1-2, bagde2023thetrappcomplexes pages 1-3, hall2024trappopathiesseveremultisystem pages 1-2). Key advances include:

  1. Structural Insights: High-resolution cryo-EM structures of complete TRAPPII and TRAPPIII complexes from yeast and metazoans have revealed the arrangement of complex-specific subunits around the TRAPPC1-containing core and mechanisms of Rab specificity determination (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 7-9).

  2. Disease Mechanisms: Expanding characterization of TRAPPopathies has highlighted the clinical importance of TRAPP complexes and provided insights into disease pathology through humanized model systems (hall2024trappopathiesseveremultisystem pages 1-2, zykaj2024ahumanizedyeast pages 1-2).

  3. Functional Specialization: Evidence continues to accumulate that TRAPPII and TRAPPIII have distinct but essential roles, with TRAPPIII being more evolutionarily conserved and TRAPPII acquiring metazoan-specific functions (galindo2023thetrappcomplexes pages 1-2, harris2021biochemicalinsightinto pages 1-5).

Summary Table

Category TRAPPC1 summary Evidence/Citation
Gene/protein identity TRAPPC1 encodes trafficking protein particle complex subunit 1; reported aliases include BET5 homolog and MUM2. It is the human ortholog of yeast Bet5 and is a conserved core TRAPP subunit shared by metazoan TRAPP complexes. (hall2024trappopathiesseveremultisystem pages 1-2, zykaj2024ahumanizedyeast pages 1-2, riedel2018thetwotrapp pages 1-2)
Protein family / structural class TRAPPC1 belongs to the conserved TRAPP small subunits/core subunits family. In metazoans, TRAPP complexes share a seven-small-subunit core that includes TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6A/B. (galindo2023thetrappcomplexes pages 3-5, harris2021biochemicalinsightinto pages 1-5, jenkins2020thesubstratespecificity pages 1-2)
Primary molecular function TRAPPC1 is not an enzyme acting alone; its primary function is as a structural/catalytic core component of the TRAPP guanine-nucleotide exchange factor (GEF) machinery that activates Rab GTPases involved in membrane trafficking. (galindo2023thetrappcomplexes pages 1-2, bagde2023thetrappcomplexes pages 1-3, hall2024trappopathiesseveremultisystem pages 1-2)
Specific role in GEF active site Structural and biochemical work places TRAPPC1 directly in the canonical Rab-binding/GEF site of the TRAPP core. The Rab-binding interface is formed mainly by TRAPPC1, TRAPPC3, and TRAPPC4, with TRAPPC5 contributing allosterically to efficient nucleotide exchange. Thus, TRAPPC1 is part of the catalytic platform that promotes GDP release and GTP loading on substrate Rabs. (harris2021biochemicalinsightinto pages 1-5, galindo2023thetrappcomplexes pages 7-9, lamber2019rabregulationby pages 1-2)
Substrate specificity TRAPPC1 contributes to the shared TRAPP active site rather than determining specificity by itself. In human/metazoan TRAPP complexes, the shared core containing TRAPPC1 supports Rab1 activation by TRAPPIII and Rab11 activation by TRAPPII; human TRAPPII also showed activity toward Rab43 and Rab19 in biochemical assays. (galindo2023thetrappcomplexes pages 1-2, jenkins2020thesubstratespecificity pages 1-2, harris2021biochemicalinsightinto pages 1-5)
What reaction is catalyzed? At the complex level, TRAPP catalyzes guanine-nucleotide exchange on Rab GTPases: conversion from the inactive GDP-bound state to the active GTP-bound state. TRAPPC1 contributes to this exchange reaction as part of the TRAPP core catalytic site. (galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 1-2, lipatova2019yptrabgtpasesand pages 1-3)
TRAPPII complex composition Human/metazoan TRAPPII contains the shared core (TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC4, TRAPPC5, TRAPPC6A/B) plus TRAPPC9 and TRAPPC10 as complex-specific subunits. TRAPPII is the principal metazoan TRAPP complex linked to Rab11 activation. (jenkins2020thesubstratespecificity pages 1-2, riedel2018thetwotrapp pages 1-2, galindo2023thetrappcomplexes pages 3-5)
TRAPPIII complex composition Human/metazoan TRAPPIII contains the same shared core including TRAPPC1, plus TRAPPC8, TRAPPC11, TRAPPC12, and TRAPPC13 as complex-specific subunits. TRAPPIII is the principal metazoan TRAPP complex linked to Rab1 activation. (galindo2023thetrappcomplexes pages 1-2, harris2021biochemicalinsightinto pages 1-5, riedel2018thetwotrapp pages 1-2)
Subcellular localization TRAPPC1 functions where TRAPP complexes act: mainly at the Golgi/early secretory pathway, especially cis-Golgi and the ER–Golgi interface; TRAPPIII is additionally linked to autophagy-related membranes/autophagosome formation. (riedel2018thetwotrapp pages 2-4, galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 1-2)
Biological pathways TRAPPC1 participates in ER-to-Golgi trafficking, intra-Golgi/secretory trafficking, Golgi-to-plasma-membrane transport, endocytic recycling (through Rab11-related TRAPPII function), and autophagy initiation/autophagosome biogenesis (through Rab1-related TRAPPIII function). (galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 1-2, lipatova2019yptrabgtpasesand pages 1-3)
Mechanistic note on specificity Recent reviews emphasize that TRAPPII and TRAPPIII use the same core catalytic site containing TRAPPC1 but achieve Rab specificity through their complex-specific large subunits and membrane context, rather than TRAPPC1 alone conferring substrate choice. (bagde2023thetrappcomplexes pages 1-3, galindo2023thetrappcomplexes pages 7-9, galindo2023thetrappcomplexes pages 1-2)
Essentiality in humans/cells TRAPPC1 is reported among the essential human TRAPP core subunits in comparative summaries of metazoan TRAPP components and cell-viability datasets. This is consistent with its central role in maintaining functional TRAPP complexes. (galindo2023thetrappcomplexes pages 3-5, harris2021biochemicalinsightinto pages 1-5)
Disease associations A TRAPPC1-associated neurodevelopmental syndrome has been reported, with biallelic variants linked to severe neurodevelopmental disorder and myopathy. Patient fibroblasts and humanized yeast studies showed membrane trafficking defects, altered Golgi morphology, and impaired secretion/autophagy that were rescued by wild-type TRAPPC1. (zykaj2024ahumanizedyeast pages 1-2)
Broader disease context TRAPPC1 belongs to the set of TRAPP genes involved in TRAPPopathies, a group of severe multisystem disorders caused by variants in TRAPP-complex genes; these disorders commonly affect neurological, skeletal, and muscular systems. (hall2024trappopathiesseveremultisystem pages 1-2, sacher2019trappopathiesanemerging pages 1-6)
Functional interpretation Overall, TRAPPC1 should be annotated primarily as a core catalytic/structural subunit of TRAPP Rab-GEF complexes that enables spatially controlled Rab activation in the secretory and autophagy pathways, rather than as an independent trafficking receptor or stand-alone enzyme. (galindo2023thetrappcomplexes pages 1-2, bagde2023thetrappcomplexes pages 1-3, galindo2023thetrappcomplexes pages 7-9)

Table: This table compiles core facts needed for functional annotation of human TRAPPC1, including identity, TRAPP-complex membership, GEF-site role, pathways, localization, essentiality, and disease relevance. It is useful as a concise evidence-backed reference for gene/protein annotation.

Conclusions

TRAPPC1 is an essential core component of TRAPP GEF complexes that activate Rab GTPases to regulate membrane trafficking and autophagy in human cells (galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 1-2). As part of the catalytic platform together with TRAPPC3 and TRAPPC4, TRAPPC1 enables GDP-to-GTP exchange on Rab1 (via TRAPPIII) and Rab11 (via TRAPPII), controlling ER-to-Golgi transport, intra-Golgi trafficking, secretion, recycling, and autophagosome formation (galindo2023thetrappcomplexes pages 1-2, lipatova2019yptrabgtpasesand pages 1-3). TRAPPC1 localizes to the Golgi apparatus and ER-Golgi interface where these trafficking events occur (riedel2018thetwotrapp pages 2-4). The protein is essential for cell viability, and pathogenic variants cause severe neurodevelopmental disorders characterized by trafficking defects, altered Golgi morphology, and impaired autophagy (zykaj2024ahumanizedyeast pages 1-2, bergen2020deficienciesinvesicular pages 1-2). Current understanding based on recent structural and functional studies positions TRAPPC1 as a central hub in the spatial organization of the early secretory pathway and cellular recycling mechanisms.

References

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Artifacts

Citations

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📚 Additional Documentation

Notes

(TRAPPC1-notes.md)

TRAPPC1 notes

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

Falcon deep research was requested with just deep-research-falcon human TRAPPC1; the provider timed out after 600 seconds and no Falcon research file was generated.

TRAPPC1 is a small core subunit of the transport protein particle (TRAPP) complex. UniProt names the protein "Trafficking protein particle complex subunit 1" and says it is "Part of the multisubunit transport protein particle (TRAPP) complex" with TRAPPC6B-TRAPPC3 interacting with TRAPPC1 to provide a core for TRAPP complex formation. The direct structural paper describes "a human Bet3-Tpc6B heterodimer" as a "core sub-complex in the assembly of TRAPP" and reports that "Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further TRAPP subunit" PMID:16828797. Mum2 is the TRAPPC1 alias in UniProt, so TRAPP-complex membership is the strongest gene-level annotation.

The main process-level role is ER-to-Golgi vesicle-mediated trafficking through TRAPP/RAB1. The TRAPP review states that TRAPP was identified as a complex that co-precipitated with Bet3, "which mediates endoplasmic reticulum (ER)-to-Golgi transport" and that TRAPP "acts as a Ypt/Rab GEF and possibly as a tether" PMID:27066478. Reactome similarly summarizes that "The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it" [Reactome:R-HSA-5694409 "Nucleotide exchange on RAB1"] and that "TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic" [Reactome:R-HSA-5694439 "COPII coat binds TRAPPCII and RAB1:GDP"]. For TRAPPC1, this supports complex membership and contribution to the complex-level RAB1 GEF/trafficking function, not an independent catalytic MF.

PN autophagy context should be used carefully. The PN mapping rationale itself says the TRAPP leaf is "autophagy-contextual" but that "shared gene-level semantics are still cleanly captured by TRAPP complex membership" [projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv]. Reactome notes that 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"]. However, the TRAPP review cautions that "the connection of the mammalian TRAPP III complex to autophagy is currently not clear" PMID:27066478. Therefore, avoid adding a broad autophagy BP for TRAPPC1 in the main review; accept TRAPPIII/TRAPP complex membership and ER/Golgi trafficking, and mention autophagy as contextual.

The coat-assembly annotations are likely over-specific. Reactome says TRAPPCII is recruited to ER-derived vesicles through TRAPPC3-SEC23/COPII interaction, and "Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP" [Reactome:R-HSA-8877475]. That supports TRAPP/RAB1-dependent ER-Golgi traffic and COPII interaction, but not that TRAPPC1 itself assembles vesicle coats. For vesicle coat assembly and COPII vesicle coat assembly, prefer modifying to ER-to-Golgi vesicle-mediated transport or marking over-annotation rather than accepting the coat-assembly process as core.

The obsolete vesicle tethering annotation should not be retained as-is. The TRAPP review explicitly says evidence that TRAPP complexes act as membrane tethers is "currently inconclusive" PMID:27066478, and the term is obsolete. Replace with ER-to-Golgi vesicle-mediated transport if the annotation is meant to capture the trafficking role.

Generic protein binding annotations from high-throughput interactome maps are not informative for TRAPPC1. Specific interaction information is better captured as TRAPP complex membership and TRAPPII/TRAPPIII protein complex annotations.

The Reactome neutrophil degranulation-derived extracellular region and azurophil granule lumen annotations are not supported by the TRAPPC1/TRAPP literature as core localization. Treat them as over-annotated unless stronger TRAPPC1-specific evidence emerges.

Annotation stance:
- Core: TRAPP complex membership (GO:0030008), including TRAPPII/TRAPPIII protein complex membership where supported.
- Complex-level molecular function to synthesize in core functions: TRAPPC1 contributes to TRAPPC complex guanyl-nucleotide exchange factor activity for RAB1 (GO:0005085), but does not independently enable the GEF activity.
- Core processes: ER-to-Golgi vesicle-mediated transport (GO:0006888) and more general vesicle-mediated transport only as a broad parent/modification target.
- Core locations: cytoplasm/cytosol, endoplasmic reticulum, Golgi apparatus.
- Modify/over-annotate: generic protein binding; vesicle coat assembly and COPII vesicle coat assembly; obsolete vesicle tethering; extracellular/azurophil granule lumen from neutrophil degranulation Reactome.

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 Proteostasis Network autophagy component recruitment context was interpreted at gene level through TRAPP/TRAPPII/TRAPPIII complex membership rather than a broad autophagy-process annotation.

Pn Notes

(TRAPPC1-pn-notes.md)

TRAPPC1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9Y5R8
  • 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: TRAPPC1 is a small core subunit of the transport protein particle (TRAPP) complex. It contributes to TRAPP complex architecture and complex-level RAB1 guanine-nucleotide exchange/vesicle-trafficking functions, especially ER-to-Golgi vesicle-mediated transport. Autophagy component recruitment is best understood through TRAPP/TRAPPII/TRAPPIII complex membership rather than independent TRAPPC1 activity.
  • Existing/core annotation action counts: ACCEPT: 15; MARK_AS_OVER_ANNOTATED: 6; MODIFY: 4

PN Consistency Summary

  • Consistency: Fully consistent. Notes, review YAML and PN converge on TRAPP-complex membership as the strongest gene-level annotation; review ACCEPTs GO:0030008 (IBA+IEA) and TRAPPII/TRAPPIII memberships, and explicitly declines a broad autophagy BP ("avoid adding a broad autophagy BP for TRAPPC1"). No contradictions.
  • PN story / NEW pressure: PN's autophagophore-recruitment story is deliberately resolved to complex membership only (GO:0030008, verified real, already in GOA). Review concurs and routes autophagy to TRAPPIII context (GO:1990072) rather than a BP, citing PMID:27066478 "the connection of the mammalian TRAPP III complex to autophagy is currently not clear." proposed_new_terms: []. Conclude: already captured; no NEW warranted.
  • Evidence alignment: Overlap. PN cites the Frontiers "TRAPP Complexes in Secretion and Autophagy" review = review's PMID:27066478 (core). Review enriches with structural (PMID:16828797) and Reactome RAB1-GEF/ER-Golgi evidence PN does not list.
  • Verdict: Fully consistent, conservative, well-curated. No edits needed.

Full Consistency Review

  • UniProt: Q9Y5R8 (TRAPP subunit 1 / Mum2) · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: Autophagy-Lysosome Pathway → Autophagophore initiation and elongation → Autophagy component recruitment to autophagophore → TRAPP complex component (1 row, ALP) ; PN-node mapping: leaf type=mapped/ok_for_propagation→GO:0030008 TRAPP complex; group=no_mapping; class=context_only/too_broad→GO:0016236 macroautophagy; branch=no_mapping. Projects GO:0030008 (already_in_goa_exact).
  • Consistency: Fully consistent. Notes, review YAML and PN converge on TRAPP-complex membership as the strongest gene-level annotation; review ACCEPTs GO:0030008 (IBA+IEA) and TRAPPII/TRAPPIII memberships, and explicitly declines a broad autophagy BP ("avoid adding a broad autophagy BP for TRAPPC1"). No contradictions.
  • PN story / NEW pressure: PN's autophagophore-recruitment story is deliberately resolved to complex membership only (GO:0030008, verified real, already in GOA). Review concurs and routes autophagy to TRAPPIII context (GO:1990072) rather than a BP, citing PMID:27066478 "the connection of the mammalian TRAPP III complex to autophagy is currently not clear." proposed_new_terms: []. Conclude: already captured; no NEW warranted.
  • Mapping strategy: Gene does not change the node. The PN node correctly avoids projecting macroautophagy (the documented "TRAPP-like overpropagation" precedent the rationale itself names) and restricts to the CC GO:0030008. Status/scope right; not broader than the review.
  • Evidence alignment: Overlap. PN cites the Frontiers "TRAPP Complexes in Secretion and Autophagy" review = review's PMID:27066478 (core). Review enriches with structural (PMID:16828797) and Reactome RAB1-GEF/ER-Golgi evidence PN does not list.
  • Verdict: Fully consistent, conservative, well-curated. No edits needed.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/TRAPPC1/TRAPPC1-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: Q9Y5R8
  • 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: Q9Y5R8
gene_symbol: TRAPPC1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TRAPPC1 is a small core subunit of the transport protein particle (TRAPP) complex. It contributes to
  TRAPP complex architecture and complex-level RAB1 guanine-nucleotide exchange/vesicle-trafficking
  functions, especially ER-to-Golgi vesicle-mediated transport. Autophagy component recruitment is
  best understood through TRAPP/TRAPPII/TRAPPIII complex membership rather than independent TRAPPC1
  activity.
existing_annotations:
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: TRAPPC1 is a core subunit of the TRAPP complex, and this cellular-component
      annotation captures the strongest gene-level function.
    action: ACCEPT
    reason: Accept as core. Direct structural and review evidence place TRAPPC1/Mum2 in
      the conserved TRAPP core, and the PN mapping also resolves the
      autophagy-contextual leaf to TRAPP complex membership.
    additional_reference_ids:
    - PMID:16828797
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - &id005
      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
    - &id006
      reference_id: PMID:16828797
      supporting_text: Bet3-Tpc6A and Bet3-Tpc6B, are able to recruit Mum2, a further
        TRAPP subunit
    - &id001
      reference_id: PMID:27066478
      supporting_text: TRAPP is a highly conserved modular multi-subunit protein complex
    - &id007
      reference_id: PMID:27066478
      supporting_text: Core TRAPP contains four small subunits that self assemble to a
        stable complex, which has a GEF activity on Ypt1
- 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: TRAPPC1 contributes to TRAPP-mediated ER-to-Golgi vesicle-mediated
      transport.
    action: ACCEPT
    reason: Accept as a core process. TRAPPC complexes activate RAB1 and facilitate
      ER-to-Golgi traffic, and TRAPPC1 is a core TRAPP subunit.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-8877475
    supported_by:
    - &id003
      reference_id: PMID:27066478
      supporting_text: Bet3, which mediates endoplasmic reticulum (ER)-to-Golgi
        transport
    - &id004
      reference_id: Reactome:R-HSA-5694439
      supporting_text: TRAPPC is a multi-subunit tethering complex that facilitates
        ER-to-Golgi traffic
    - &id002
      reference_id: Reactome:R-HSA-5694409
      supporting_text: The TRAPPC complex acts as a guanine-nucleotide exchange factor
        for RAB1, activating it
    - &id008
      reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
        GEF activity of the multisubunit TRAPPC complexes II and III
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: TRAPPC1 is a cytoplasmic/cytosolic TRAPP subunit associated with
      membrane-trafficking complexes.
    action: ACCEPT
    reason: Accept as a broad supported cellular location for a peripheral
      trafficking-complex subunit.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694409
    supported_by:
    - *id001
    - *id002
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: TRAPPC1 participates in ER-derived vesicle trafficking and UniProt maps it
      to the endoplasmic reticulum.
    action: ACCEPT
    reason: Accept as a supported location for the ER-to-Golgi trafficking context.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694439
    supported_by:
    - *id003
    - *id004
    - &id010
      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:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: TRAPPC1 participates in ER-to-Golgi transport and is associated with
      Golgi/cis-Golgi TRAPP trafficking functions.
    action: ACCEPT
    reason: Accept as a supported Golgi-location annotation for TRAPP-mediated
      ER-to-Golgi trafficking. Falcon deep research corroborates Golgi/ER-Golgi-interface
      localization for TRAPPC1 as part of TRAPP complexes (with cis-Golgi labeling reported
      for TRAPP-specific subunits in Drosophila).
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694439
    - file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
    supported_by:
    - *id003
    - *id004
    - &id015
      reference_id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
      supporting_text: TRAPPC1, as part of TRAPP complexes, localizes primarily to the
        Golgi apparatus and the endoplasmic reticulum (ER)-Golgi interface
- term:
    id: GO:0016192
    label: vesicle-mediated transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Vesicle-mediated transport is true but too broad for TRAPPC1; the evidence
      supports the ER-to-Golgi/TRAPP/RAB1 pathway more specifically.
    action: MODIFY
    reason: Modify to the more specific ER-to-Golgi vesicle-mediated transport term.
    proposed_replacement_terms:
    - &id009
      id: GO:0006888
      label: endoplasmic reticulum to Golgi vesicle-mediated transport
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694439
    supported_by:
    - *id003
    - *id004
    - *id002
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: TRAPPC1 is a core subunit of the TRAPP complex, and this cellular-component
      annotation captures the strongest gene-level function.
    action: ACCEPT
    reason: Accept as core. Direct structural and review evidence place TRAPPC1/Mum2 in
      the conserved TRAPP core, and the PN mapping also resolves the
      autophagy-contextual leaf to TRAPP complex membership.
    additional_reference_ids:
    - PMID:16828797
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - *id005
    - *id006
    - *id001
    - *id007
- 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 TRAPPC1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      by TRAPP/TRAPPII/TRAPPIII complex membership rather than 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 TRAPPC1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      by TRAPP/TRAPPII/TRAPPIII complex membership rather than 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 TRAPPC1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      by TRAPP/TRAPPII/TRAPPIII complex membership rather than 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 TRAPPC1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. Specific interaction biology should be represented
      by TRAPP/TRAPPII/TRAPPIII complex membership rather than GO:0005515.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: located_in
  review:
    summary: TRAPPC1 is a cytoplasmic/cytosolic TRAPP subunit associated with
      membrane-trafficking complexes.
    action: ACCEPT
    reason: Accept as a broad supported cellular location for a peripheral
      trafficking-complex subunit.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694409
    supported_by:
    - *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: TRAPPC1 contributes to TRAPP-mediated ER-to-Golgi vesicle-mediated
      transport.
    action: ACCEPT
    reason: Accept as a core process. TRAPPC complexes activate RAB1 and facilitate
      ER-to-Golgi traffic, and TRAPPC1 is a core TRAPP subunit.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id004
    - *id002
    - *id008
    - &id014
      reference_id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
      supporting_text: TRAPPIII activates Rab1 to regulate transport of newly synthesized
        proteins from the ER to the Golgi apparatus
- term:
    id: GO:0006901
    label: vesicle coat assembly
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: TRAPPC complexes interact with vesicle coats and RAB1 on ER-derived
      vesicles, but TRAPPC1 is not a coat-assembly factor.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport. The coat-related evidence
      supports recruitment/traffic context rather than direct vesicle coat assembly.
    proposed_replacement_terms:
    - *id009
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id010
    - &id011
      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 places TRAPPCII near SEC23/COPII vesicles, but does not
      show TRAPPC1 assembling the COPII coat.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport, which captures the
      supported TRAPP/COPII/RAB1 trafficking role without overclaiming coat assembly.
    proposed_replacement_terms:
    - *id009
    additional_reference_ids:
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id010
    - *id011
- term:
    id: GO:0099022
    label: obsolete vesicle tethering
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: This annotation uses an obsolete vesicle-tethering term, and the cited
      TRAPP review cautions that direct TRAPP tethering evidence is inconclusive.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport, the safer supported
      process for TRAPPC1/TRAPP complex function.
    proposed_replacement_terms:
    - *id009
    additional_reference_ids:
    - PMID:27066478
    - 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
    - *id004
- term:
    id: GO:1990071
    label: TRAPPII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC1 is represented in human TRAPPII complex models and ComplexPortal
      annotations.
    action: ACCEPT
    reason: Accept as a supported TRAPP complex subtype membership, while recognizing
      that gene-level process conclusions should remain centered on ER-Golgi transport
      and TRAPP/RAB1 function.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-8877475
    supported_by:
    - *id001
    - *id007
    - *id008
    - &id013
      reference_id: Reactome:R-HSA-8877475
      supporting_text: Interaction of TRAAPPCII with RAB1:GDP promotes release of GDP,
        allowing GTP to bind
- term:
    id: GO:1990072
    label: TRAPPIII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC1 is represented in human TRAPPIII complex models; this is the TRAPP
      subtype most relevant to the PN autophagy recruitment context.
    action: ACCEPT
    reason: Accept as supported complex membership. The autophagy implication should be
      treated as context for TRAPPIII/RAB1 biology, not as a broad autophagy BP
      annotation for TRAPPC1. Falcon deep research likewise links autophagosome
      formation to the TRAPPIII holo-complex rather than to TRAPPC1 specifically.
    additional_reference_ids:
    - PMID:27066478
    - Reactome:R-HSA-8877475
    - file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
    supported_by:
    - *id001
    - *id007
    - 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
    - reference_id: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
      supporting_text: TRAPPIII has been localized to autophagy-related membranes where
        it participates in autophagosome formation
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798751
  qualifier: located_in
  review:
    summary: The extracellular-region annotation comes from a broad Reactome
      neutrophil-degranulation event and is not supported as a core TRAPPC1
      localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. TRAPPC1 is a TRAPP trafficking-complex subunit
      associated with cytosol/ER/Golgi contexts, not a secreted extracellular protein.
    additional_reference_ids:
    - Reactome:R-HSA-6798751
    supported_by:
    - &id012
      reference_id: Reactome:R-HSA-6798751
      supporting_text: Azurophil or primary granules were originally defined by their
        high content of myeloperoxidase
- term:
    id: GO:0035578
    label: azurophil granule lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6798751
  qualifier: located_in
  review:
    summary: The azurophil-granule-lumen annotation is inherited from a broad Reactome
      degranulation context and lacks TRAPPC1-specific support.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. It does not fit the core TRAPPC1/TRAPP complex
      localization or trafficking function.
    additional_reference_ids:
    - Reactome:R-HSA-6798751
    supported_by:
    - *id012
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694409
  qualifier: located_in
  review:
    summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic
      face of ER-Golgi trafficking reactions.
    action: ACCEPT
    reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id004
    - *id002
    - *id008
    - *id013
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694418
  qualifier: located_in
  review:
    summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic
      face of ER-Golgi trafficking reactions.
    action: ACCEPT
    reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id004
    - *id002
    - *id008
    - *id013
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694439
  qualifier: located_in
  review:
    summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic
      face of ER-Golgi trafficking reactions.
    action: ACCEPT
    reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id004
    - *id002
    - *id008
    - *id013
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5694441
  qualifier: located_in
  review:
    summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic
      face of ER-Golgi trafficking reactions.
    action: ACCEPT
    reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id004
    - *id002
    - *id008
    - *id013
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8877475
  qualifier: located_in
  review:
    summary: Reactome places TRAPPC1-containing TRAPPC events in the cytosol/cytosolic
      face of ER-Golgi trafficking reactions.
    action: ACCEPT
    reason: Accept as a supported location for TRAPPC/RAB1 trafficking reactions.
    additional_reference_ids:
    - Reactome:R-HSA-5694409
    - Reactome:R-HSA-5694439
    - Reactome:R-HSA-8877475
    supported_by:
    - *id004
    - *id002
    - *id008
    - *id013
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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID: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: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-6798751
  title: Exocytosis of azurophil granule lumen proteins
  findings: []
- id: Reactome:R-HSA-8877475
  title: TRAPPC complexes exchange GTP for GDP on RAB1
  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: file:human/TRAPPC1/TRAPPC1-deep-research-falcon.md
  title: Falcon deep research report for TRAPPC1
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: >-
      LLM-synthesized (Edison/Falcon) deep-research report compiling current understanding
      of TRAPPC1. Useful corroboration for established TRAPP-complex biology (core subunit
      membership with TRAPPC3/TRAPPC4 at the Rab-binding/GEF site; TRAPPIII activates RAB1
      for ER-to-Golgi transport and autophagy; TRAPPII activates RAB11; Golgi/ER-Golgi and
      cis-Golgi localization). IMPORTANT caveat: the report repeatedly attributes whole-TRAPP
      holo-complex functions (GEF activity, Rab specificity, autophagosome formation) to the
      TRAPPC1 subunit specifically. Subunit-specific evidence for TRAPPC1 is limited to its
      structural placement in the conserved core (consistent with PMID:16828797 Bet3-Tpc6B-Mum2
      sub-complex) and to patient-variant studies (Zykaj 2024; Van Bergen 2020) showing reduced
      TRAPPC1 destabilizes the complex and impairs trafficking/autophagy. GEF catalysis is a
      holo-complex property, not an independent TRAPPC1 activity. Citations are secondary
      reviews (Galindo & Munro 2023; Bagde & Fromme 2023; Sacher 2019; Hall 2024) not
      independently verified here.
core_functions:
- contributes_to_molecular_function:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  in_complex:
    id: GO:0030008
    label: TRAPP complex
  description: TRAPPC1 contributes a small core subunit to TRAPP complexes, supporting
    complex-level RAB1 guanine-nucleotide exchange and ER-to-Golgi trafficking. Its role
    is best represented as contribution to the TRAPP complex activity rather than an
    independent catalytic 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:0005783
    label: endoplasmic reticulum
  - id: GO:0005794
    label: Golgi apparatus
  supported_by:
  - *id005
  - *id006
  - *id003
  - *id004
  - *id002
  - *id008
proposed_new_terms: []
suggested_questions:
- question: Should TRAPPC1 and other shared TRAPP subunits receive contributes_to
    annotations for TRAPPC complex RAB1 guanine-nucleotide exchange activity?
  experts:
  - GO transport editors
  - Reactome TRAPP curators
- question: Should TRAPP subunit PN autophagy contexts be captured only as TRAPPIII
    complex membership unless direct human autophagophore/PAS evidence is available?
  experts:
  - GO autophagy editors
  - GO cellular-component editors
- question: Should current TRAPPC1 vesicle coat assembly and obsolete vesicle tethering
    annotations be replaced by ER-to-Golgi vesicle-mediated transport or more specific
    TRAPP/RAB1 terms?
  experts:
  - ComplexPortal curators
  - GO transport editors
suggested_experiments:
- description: Reconstitute human TRAPPII/TRAPPIII complexes with and without TRAPPC1
    and measure RAB1 GDP-GTP exchange activity.
  experiment_type: complex reconstitution and RAB1 GEF assay
  hypothesis: TRAPPC1 is required as a core scaffold subunit for TRAPPC complex-level
    RAB1 GEF activity rather than acting as an independent catalytic subunit.
- description: Use TRAPPC1 knockout and rescue cells to assay ER-to-Golgi cargo
    transport, COPII-vesicle association, and Golgi localization of TRAPP components.
  experiment_type: cellular trafficking rescue assay
  hypothesis: TRAPPC1 loss disrupts TRAPP-dependent ER-to-Golgi vesicle-mediated
    transport by destabilizing or mislocalizing TRAPP complexes.
- description: Measure ATG9 localization and autophagophore initiation markers in
    TRAPPC1 rescue cells while separately monitoring ER-to-Golgi trafficking defects.
  experiment_type: autophagy-context separation assay
  hypothesis: Any TRAPPC1 autophagy phenotype is mediated through TRAPPIII/RAB1
    trafficking context and should not be generalized to a broad autophagy core function
    without direct evidence.