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.
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: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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