TRAPPC5

UniProt ID: Q8IUR0
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TRAPPC5 is the human Trs31 ortholog and a small TRAPP core subunit. It supports TRAPP complex architecture, complex-level RAB1 guanine-nucleotide exchange, and ER-to-Golgi vesicle-mediated transport. Autophagy-related effects are best understood through TRAPP/TRAPPII/TRAPPIII complex membership and ER-Golgi trafficking rather than an independent TRAPPC5-specific autophagy function.

Existing Annotations Review

GO Term Evidence Action Reason
GO:1990071 TRAPPII protein complex
IBA
GO_REF:0000033
ACCEPT
Summary: TRAPPC5 is represented in TRAPPII protein complex through the shared TRAPP core.
Reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit.
Supporting Evidence:
PMID:21525244
with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
PMID:27066478
TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:1990072 TRAPPIII protein complex
IBA
GO_REF:0000033
ACCEPT
Summary: TRAPPC5 is represented in TRAPPIII protein complex through the shared TRAPP core.
Reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit.
Supporting Evidence:
PMID:21525244
with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
PMID:27066478
TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
IBA
GO_REF:0000033
ACCEPT
Summary: TRAPPC5 contributes to TRAPP-dependent ER-to-Golgi trafficking.
Reason: Accept as a core process. TRAPPC5 is a core TRAPP subunit, and TRAPP complex/RAB1 biology supports ER-to-Golgi vesicle-mediated transport.
Supporting Evidence:
PMID:21525244
in ER-to-Golgi trafficking at a very early stage
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
GO:1990070 TRAPPI protein complex
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: TRAPPI protein complex is problematic as a human TRAPPC5 annotation.
Reason: Mark as over-annotated. TRAPPC5 is a yeast TRAPP I core ortholog, but the mammalian literature questions the existence of a discrete TRAPP I complex in vivo.
Supporting Evidence:
PMID:21525244
absence of a TRAPP I-equivalent complex in mammalian cells
PMID:27066478
TRAPP I cannot be separated from the mammalian TRAPP II and its existence in vivo in mammalian cells is currently in question
PMID:27066478
there is currently no evidence for the existence of TRAPP I in mammalian cells
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000044
ACCEPT
Summary: endoplasmic reticulum localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions. ORGANELLES check (2026-11-06): the IEA maps the UniProt location "Endoplasmic reticulum {ECO:0000250}", a by-similarity line with no named source (UniProt places yeast Trs31p, Q03337, at the cis-Golgi network and ER). The claim holds by complex membership: TRAPPC5 is a core TRAPP subunit with TRAPPC3, whose endogenous mammalian ortholog is concentrated on Sec31p-marked transitional ER (ER exit sites) by immuno-EM (PMID:16880271), and the TRAPPC12 paper summarises that TRAPPC3 localizes to the transitional ER (PMID:21525244). No assay places TRAPPC5 itself at the ER. It is a soluble peripheral subunit with no TM segment or signal peptide, so the ER pool is on the cytosolic face; with only the complex-membership line, no ER exit site, membrane or lumen row is added (TRAPPC3 carries the NEW ER exit site row). Kept ACCEPT because TRAPPC5 is an obligate TRAPP core subunit and the complex's GEF and tethering activity is exercised at the ER exit site (PMID:16880271), which is why core_functions also names the ER.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
PMID:21525244
C3, a core component of the complex, localizes to the transitional ER
PMID:16880271
Immuno-EM in NRK cells confirmed that mBet3p (5-nm gold particles) resides on the tER region labeled with Sec31p (10-nm gold particles).
GO:0005794 Golgi apparatus
IEA
GO_REF:0000044
ACCEPT
Summary: Golgi apparatus localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
GO:0030008 TRAPP complex
IEA
GO_REF:0000120
ACCEPT
Summary: TRAPPC5 is a human TRAPP core subunit.
Reason: Accept as core cellular-component membership. Mammalian TRAPP component work identifies C5/TRAPPC5 among known human TRAPP components.
Supporting Evidence:
PMID:21525244
with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
PMID:21525244
known human TRAPP components, including C3, C4, and C5
PMID:27066478
A single TRAPP complex purified from mammalian cell lysate contains all the known subunits
GO:0048193 Golgi vesicle transport
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Golgi vesicle transport is plausible TRAPP context but less specific than ER-to-Golgi transport for TRAPPC5.
Reason: Keep as non-core. The core process is ER-to-Golgi/TRAPP/RAB1 transport; broader Golgi vesicle transport is a reasonable parent/context but not the most specific function.
Supporting Evidence:
PMID:21525244
in ER-to-Golgi trafficking at a very early stage
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC5 function.
Reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
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 TRAPPC5 function.
Reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC5 function.
Reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
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 TRAPPC5 function.
Reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
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 TRAPPC5 function.
Reason: Mark as over-annotated. Proteome-scale interactions and TRAPP-subunit interactions should be interpreted through TRAPP complex membership, not generic protein binding.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
GO:0005737 cytoplasm
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
ACCEPT
Summary: cytoplasm localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
PMID:21525244
known human TRAPP components, including C3, C4, and C5
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
ACCEPT
Summary: TRAPPC5 contributes to TRAPP-dependent ER-to-Golgi trafficking.
Reason: Accept as a core process. TRAPPC5 is a core TRAPP subunit, and TRAPP complex/RAB1 biology supports ER-to-Golgi vesicle-mediated transport.
Supporting Evidence:
PMID:21525244
in ER-to-Golgi trafficking at a very early stage
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
GO:0006901 vesicle coat assembly
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
MODIFY
Summary: vesicle coat assembly overstates TRAPPC5 as a coat-assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC5 participates in TRAPP-dependent trafficking, but the evidence does not show direct coat assembly by TRAPPC5.
Supporting Evidence:
PMID:21525244
in ER-to-Golgi trafficking at a very early stage
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
TRAPPCII is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein SEC23
GO:0048208 COPII vesicle coat assembly
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
MODIFY
Summary: COPII vesicle coat assembly overstates TRAPPC5 as a coat-assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC5 participates in TRAPP-dependent trafficking, but the evidence does not show direct coat assembly by TRAPPC5.
Supporting Evidence:
PMID:21525244
in ER-to-Golgi trafficking at a very early stage
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
TRAPPCII is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein SEC23
GO:0099022 obsolete vesicle tethering
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
MODIFY
Summary: The obsolete vesicle-tethering annotation should not be kept as-is for TRAPPC5.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC5/TRAPP process. Mammalian TRAPP tethering remains unresolved and the term is obsolete.
Supporting Evidence:
PMID:27066478
evidence that any TRAPP complex acts as a membrane tether is currently inconclusive
PMID:21525244
in ER-to-Golgi trafficking at a very early stage
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
GO:1990071 TRAPPII protein complex
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
ACCEPT
Summary: TRAPPC5 is represented in TRAPPII protein complex through the shared TRAPP core.
Reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit.
Supporting Evidence:
PMID:21525244
with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
PMID:27066478
TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:1990072 TRAPPIII protein complex
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
ACCEPT
Summary: TRAPPC5 is represented in TRAPPIII protein complex through the shared TRAPP core.
Reason: Accept as complex-context membership. Human TRAPPII/TRAPPIII are modeled as core TRAPP plus accessory subunits, and TRAPPC5 is a small core subunit.
Supporting Evidence:
PMID:21525244
with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
PMID:27066478
TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13
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:0030008 TRAPP complex
IDA
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol...
ACCEPT
Summary: TRAPPC5 is a human TRAPP core subunit.
Reason: Accept as core cellular-component membership. Mammalian TRAPP component work identifies C5/TRAPPC5 among known human TRAPP components.
Supporting Evidence:
PMID:21525244
with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
PMID:21525244
known human TRAPP components, including C3, C4, and C5
PMID:27066478
A single TRAPP complex purified from mammalian cell lysate contains all the known subunits
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694409
ACCEPT
Summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694418
ACCEPT
Summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694439
ACCEPT
Summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0005829 cytosol
TAS
Reactome:R-HSA-5694441
ACCEPT
Summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0005829 cytosol
TAS
Reactome:R-HSA-8877475
ACCEPT
Summary: cytosol localization is consistent with TRAPPC5 as a soluble/peripheral TRAPP trafficking subunit.
Reason: Accept as a supported location for TRAPPC5-containing TRAPP reactions.
Supporting Evidence:
Reactome:R-HSA-5694409
The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
Reactome:R-HSA-5694439
TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III

Core Functions

TRAPPC5 contributes the Trs31-like small 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.

Supporting Evidence:
  • PMID:21525244
    with the mammalian orthologues named TRAPPC1, TRAPPC2, TRAPPC3, TRAPPC4, TRAPPC5, and TRAPPC6a/b
  • PMID:21525244
    known human TRAPP components, including C3, C4, and C5
  • PMID:21525244
    These activities are dependent on the subunits Bet3p, Trs31p, Trs23p, and Bet5p
  • Reactome:R-HSA-5694409
    The TRAPPC complex acts as a guanine-nucleotide exchange factor for RAB1, activating it
  • Reactome:R-HSA-8877475
    RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
  • PMID:21525244
    in ER-to-Golgi trafficking at a very early stage
  • Reactome:R-HSA-5694439
    TRAPPC is a multi-subunit tethering complex that facilitates ER-to-Golgi traffic

References

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Suggested Questions for Experts

Q: Should TRAPPC5 receive a contributes_to RAB1 guanine-nucleotide exchange factor activity annotation based on Trs31-dependent yeast GEF evidence plus mammalian TRAPP complex models?

Suggested experts: GO transport editors, Reactome TRAPP curators

Q: Should human TRAPPI protein complex annotations be removed or replaced when the literature questions a discrete mammalian TRAPP I complex?

Suggested experts: GO cellular-component editors, ComplexPortal curators

Q: Should PN TRAPP-component autophagy context be represented only by TRAPPIII membership for TRAPPC5 unless TRAPPC5-specific autophagy experiments are available?

Suggested experts: GO autophagy editors, TRAPP biology experts

Suggested Experiments

Experiment: Reconstitute TRAPPC5-containing human TRAPP complexes and measure RAB1 GDP-GTP exchange after TRAPPC5 depletion or interface mutation.

Hypothesis: TRAPPC5 is required as a core TRAPP subunit for complex-level RAB1 GEF activity.

Type: complex reconstitution and RAB1 GEF assay

Experiment: Use TRAPPC5 knockout/rescue cells to assay ER-to-Golgi cargo transport, TRAPP complex stability, and Golgi/ER localization of TRAPP subunits.

Hypothesis: TRAPPC5 loss disrupts TRAPP-dependent ER-to-Golgi vesicle-mediated transport by destabilizing or mislocalizing the TRAPP core.

Type: cellular trafficking rescue assay

Experiment: Biochemically separate human TRAPPII and TRAPPIII pools containing TRAPPC5 and test whether any discrete TRAPPI-like pool exists in vivo.

Hypothesis: TRAPPC5 is present in human TRAPPII/TRAPPIII assemblies, while a discrete mammalian TRAPPI complex is absent or not stable in vivo.

Type: complex purification and native fractionation

πŸ“š Additional Documentation

Notes

(TRAPPC5-notes.md)

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Pn Notes

(TRAPPC5-pn-notes.md)

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