TRAPPC12

UniProt ID: Q8WVT3
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

TRAPPC12/TRAMM/TTC-15 is a moonlighting metazoan TRAPP/TRAPPIII-associated protein. In interphase it participates in TRAPP-dependent early secretory traffic between ER, ERGIC, and Golgi. During mitosis it leaves the TRAPP context and supports chromosome congression, kinetochore stability, and CENP-E recruitment. Its shared cellular roles are TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking; direct TRAPPC12-specific autophagy evidence is limited.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005794 Golgi apparatus
IBA
GO_REF:0000033 		ACCEPT
Summary: Golgi apparatus localization/activity context is supported for TRAPPC12/TRAPP trafficking.
Reason: Accept as supported location/context. TRAPPC12 is mainly observed in Golgi/perinuclear TRAPP context, and TRAPPC12 disease fibroblasts show rescued Golgi fragmentation and delayed ER-to-Golgi/Golgi transport.
Supporting Evidence:
PMID:21525244
C12 is largely found in punctae throughout the cell
PMID:21525244
highly punctate with an obvious concentration of the punctae in the perinuclear region
PMID:21525244
RNAi against C8, C11, or C12 resulted in Golgi fragmentation
PMID:28777934
Fibroblasts derived from all three individuals showed a fragmented Golgi
PMID:28777934
Protein transport from the endoplasmic reticulum to and through the Golgi was delayed
GO:0030008 TRAPP complex
IBA
GO_REF:0000033 		ACCEPT
Summary: TRAPPC12 is a mammalian TRAPP complex component.
Reason: Accept as core cellular-component membership. TRAPPC12/TTC-15 is identified as a stable mammalian TRAPP interactor, and UniProt describes it as a component of the multisubunit TRAPP complex.
Supporting Evidence:
PMID:21525244
TTC-15 (now designated TRAPPC12)
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:21525244
endogenous C12 was observed to elute in the same high-molecular-weight pool as TRAPP
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Component of the multisubunit TRAPP (transport protein
PMID:25918224
TRAMM cycles between its role in TRAPP in interphase cells
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: Nuclear localization is supported for the mitotic TRAMM/TRAPPC12 branch.
Reason: Accept as a supported location for the moonlighting mitotic role. TRAMM cofractionates with a nuclear marker, associates weakly with mitotic chromosomes/kinetochores, and UniProt cites nuclear localization from PMID:25918224.
Supporting Evidence:
PMID:25918224
cellular fractionation indicated that a small but reproducible amount of TRAMM cofractionated with a nuclear marker
PMID:25918224
Small amounts of TRAMM associated with chromosomes
PMID:25918224
small amounts of TRAMM on chromosomes associate with ACA-positive structures representing the kinetochore
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Nucleus {ECO:0000269|PubMed:25918224}
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
IEA
GO_REF:0000044 		ACCEPT
Summary: ERGIC localization/colocalization is supported for early TRAPP secretory traffic.
Reason: Accept as supported location/context. TRAPPC12/C12 is part of the TRAPP early secretory pathway, and C11/C12 depletion arrests VSV-G cargo in a BFA-resistant ERGIC-associated compartment.
Supporting Evidence:
PMID:21525244
knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Endoplasmic reticulum-Golgi intermediate
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 TRAPPC12 function.
Reason: Mark as over-annotated. TRAPPC12 interactions are better represented as TRAPP/TRAPPIII complex membership or as CENP-E recruitment to kinetochore, not as generic protein binding.
Supporting Evidence:
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:25918224
prevented the recruitment of CENP-E to the kinetochore
PMID:25918224
TRAMM-5D was able to recruit more CENP-E to kinetochores
GO:0005737 cytoplasm
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: Cytoplasm is a broad but reasonable location for TRAPPC12 soluble/peripheral TRAPP biology.
Reason: Accept as broad supported location/context. TRAPPC12 has cytoplasmic/perinuclear/Golgi pools in early secretory traffic and a distinct mitotic pool.
Supporting Evidence:
PMID:21525244
highly punctate with an obvious concentration of the punctae in the perinuclear region
PMID:21525244
C12 is largely found in punctae throughout the cell
PMID:25918224
the supernatant was kept as the cytoplasmic fraction
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC12 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII.
Reason: Accept as a core process. Direct TRAPPC12 evidence supports early ER-to-Golgi trafficking, ERGIC cargo arrest, Golgi fragmentation on depletion, and delayed ER-to-Golgi/Golgi transport in patient fibroblasts.
Supporting Evidence:
PMID:21525244
ER-to-Golgi trafficking at a very early stage
PMID:21525244
knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
PMID:21525244
These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway
PMID:28777934
Protein transport from the endoplasmic reticulum to and through the Golgi was delayed
file:human/TRAPPC12/TRAPPC12-uniprot.txt
endoplasmic reticulum to Golgi apparatus trafficking at a very early
Reactome:R-HSA-8877475
RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
GO:0048208 COPII vesicle coat assembly
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		MODIFY
Summary: The COPII coat assembly annotation captures early secretory context but overstates TRAPPC12 as a coat-assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC12 evidence supports early ER/ERGIC/Golgi trafficking in COPII-associated anterograde traffic, not direct assembly of the COPII vesicle coat.
Supporting Evidence:
PMID:21525244
ER-to-Golgi trafficking at a very early stage
PMID:21525244
knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
PMID:28777934
Protein transport from the endoplasmic reticulum to and through the Golgi was delayed
Reactome:R-HSA-8877475
RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
GO:0099022 obsolete vesicle tethering
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		MODIFY
Summary: The obsolete vesicle-tethering annotation should not be retained as-is.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC12/TRAPP process. Mammalian TRAPP tethering remains unresolved and this GO term is obsolete.
Supporting Evidence:
PMID:27066478
evidence that any TRAPP complex acts as a membrane tether is currently inconclusive
PMID:21525244
ER-to-Golgi trafficking at a very early stage
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
PMID:28777934
Protein transport from the endoplasmic reticulum to and through the Golgi was delayed
GO:1990072 TRAPPIII protein complex
NAS
PMID:27066478
TRAPP Complexes in Secretion and Autophagy. 		ACCEPT
Summary: TRAPPC12 is modeled as a mammalian TRAPPIII-associated subunit.
Reason: Accept as core complex membership in the PN TRAPP bucket. The review literature assigns TRAPPC12 to mammalian TRAPPIII, and Reactome models TRAPPCIII in RAB1/autophagy context.
Supporting Evidence:
PMID:27066478
TRAPP III, which contains core TRAPP plus TrappC8, 11-13
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
Reactome:R-HSA-8877475
RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS)
GO:0005654 nucleoplasm
IDA
GO_REF:0000052 		MODIFY
Summary: Nucleoplasm is more specific than the accessible TRAMM/TRAPPC12 evidence supports.
Reason: Modify to nucleus. The seeded HPA-derived row may reflect nuclear immunofluorescence, but the accessible full-text evidence supports nuclear/chromosome/kinetochore association rather than nucleoplasm specifically.
Proposed replacements: nucleus
Supporting Evidence:
PMID:25918224
cellular fractionation indicated that a small but reproducible amount of TRAMM cofractionated with a nuclear marker
PMID:25918224
Small amounts of TRAMM associated with chromosomes
PMID:25918224
small amounts of TRAMM on chromosomes associate with ACA-positive structures representing the kinetochore
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Nucleus {ECO:0000269|PubMed:25918224}
GO:0005794 Golgi apparatus
IDA
GO_REF:0000052 		ACCEPT
Summary: Golgi apparatus localization/activity context is supported for TRAPPC12/TRAPP trafficking.
Reason: Accept as supported location/context. TRAPPC12 is mainly observed in Golgi/perinuclear TRAPP context, and TRAPPC12 disease fibroblasts show rescued Golgi fragmentation and delayed ER-to-Golgi/Golgi transport.
Supporting Evidence:
PMID:21525244
C12 is largely found in punctae throughout the cell
PMID:21525244
highly punctate with an obvious concentration of the punctae in the perinuclear region
PMID:21525244
RNAi against C8, C11, or C12 resulted in Golgi fragmentation
PMID:28777934
Fibroblasts derived from all three individuals showed a fragmented Golgi
PMID:28777934
Protein transport from the endoplasmic reticulum to and through the Golgi was delayed
GO:0005515 protein binding
IPI
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC12 function.
Reason: Mark as over-annotated. TRAPPC12 interactions are better represented as TRAPP/TRAPPIII complex membership or as CENP-E recruitment to kinetochore, not as generic protein binding.
Supporting Evidence:
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:25918224
prevented the recruitment of CENP-E to the kinetochore
PMID:25918224
TRAMM-5D was able to recruit more CENP-E to kinetochores
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
IMP
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		ACCEPT
Summary: ERGIC localization/colocalization is supported for early TRAPP secretory traffic.
Reason: Accept as supported location/context. TRAPPC12/C12 is part of the TRAPP early secretory pathway, and C11/C12 depletion arrests VSV-G cargo in a BFA-resistant ERGIC-associated compartment.
Supporting Evidence:
PMID:21525244
knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Endoplasmic reticulum-Golgi intermediate
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
IMP
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		ACCEPT
Summary: TRAPPC12 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII.
Reason: Accept as a core process. Direct TRAPPC12 evidence supports early ER-to-Golgi trafficking, ERGIC cargo arrest, Golgi fragmentation on depletion, and delayed ER-to-Golgi/Golgi transport in patient fibroblasts.
Supporting Evidence:
PMID:21525244
ER-to-Golgi trafficking at a very early stage
PMID:21525244
knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
PMID:21525244
TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
PMID:21525244
These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway
PMID:28777934
Protein transport from the endoplasmic reticulum to and through the Golgi was delayed
file:human/TRAPPC12/TRAPPC12-uniprot.txt
endoplasmic reticulum to Golgi apparatus trafficking at a very early
Reactome:R-HSA-8877475
RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
GO:0007030 Golgi organization
IMP
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		KEEP AS NON CORE
Summary: Golgi organization is a direct TRAPPC12-depletion/disease phenotype but is secondary to early secretory trafficking.
Reason: Keep as non-core. Golgi fragmentation is a useful readout of TRAPPC12/TRAPP disruption and is disease-relevant, while the core process is ER-to-ERGIC/Golgi trafficking.
Supporting Evidence:
PMID:21525244
RNAi against C8, C11, or C12 resulted in Golgi fragmentation
PMID:28777934
Fibroblasts derived from all three individuals showed a fragmented Golgi
PMID:21525244
These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway
GO:0048471 perinuclear region of cytoplasm
IMP
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		ACCEPT
Summary: Perinuclear cytoplasmic localization is supported for interphase TRAPPC12/Golgi puncta.
Reason: Accept as a supported location for the interphase trafficking pool of TRAPPC12.
Supporting Evidence:
PMID:21525244
highly punctate with an obvious concentration of the punctae in the perinuclear region
PMID:21525244
C12 is largely found in punctae throughout the cell
PMID:25918224
TRAMM is largely localized to a perinuclear region representing the Golgi
GO:0030008 TRAPP complex
IDA
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a rol... 		ACCEPT
Summary: TRAPPC12 is a mammalian TRAPP complex component.
Reason: Accept as core cellular-component membership. TRAPPC12/TTC-15 is identified as a stable mammalian TRAPP interactor, and UniProt describes it as a component of the multisubunit TRAPP complex.
Supporting Evidence:
PMID:21525244
TTC-15 (now designated TRAPPC12)
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:21525244
endogenous C12 was observed to elute in the same high-molecular-weight pool as TRAPP
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Component of the multisubunit TRAPP (transport protein
PMID:25918224
TRAMM cycles between its role in TRAPP in interphase cells
GO:0000776 kinetochore
IDA
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinet... 		ACCEPT
Summary: Kinetochore localization is weak/transient but directly supported for mitotic TRAMM/TRAPPC12.
Reason: Accept as supported. The full-text paper shows small amounts of TRAMM on chromosomes associated with ACA-positive kinetochore structures and frames this as a weak/transient kinetochore association.
Supporting Evidence:
PMID:25918224
Small amounts of TRAMM associated with chromosomes
PMID:25918224
small amounts of TRAMM on chromosomes associate with ACA-positive structures representing the kinetochore
PMID:25918224
TRAMM appears to have a weak or transient association with kinetochores
file:human/TRAPPC12/TRAPPC12-uniprot.txt
the recruitment of CENPE to the kinetochores
GO:0005515 protein binding
IPI
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinet... 		MARK AS OVER ANNOTATED
Summary: Generic protein binding is not informative for TRAPPC12 function.
Reason: Mark as over-annotated. TRAPPC12 interactions are better represented as TRAPP/TRAPPIII complex membership or as CENP-E recruitment to kinetochore, not as generic protein binding.
Supporting Evidence:
PMID:21525244
C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
PMID:21525244
These results firmly establish the newly identified proteins as stable TRAPP interactors
PMID:25918224
prevented the recruitment of CENP-E to the kinetochore
PMID:25918224
TRAMM-5D was able to recruit more CENP-E to kinetochores
GO:0005634 nucleus
IDA
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinet... 		ACCEPT
Summary: Nuclear localization is supported for the mitotic TRAMM/TRAPPC12 branch.
Reason: Accept as a supported location for the moonlighting mitotic role. TRAMM cofractionates with a nuclear marker, associates weakly with mitotic chromosomes/kinetochores, and UniProt cites nuclear localization from PMID:25918224.
Supporting Evidence:
PMID:25918224
cellular fractionation indicated that a small but reproducible amount of TRAMM cofractionated with a nuclear marker
PMID:25918224
Small amounts of TRAMM associated with chromosomes
PMID:25918224
small amounts of TRAMM on chromosomes associate with ACA-positive structures representing the kinetochore
file:human/TRAPPC12/TRAPPC12-uniprot.txt
Nucleus {ECO:0000269|PubMed:25918224}
GO:0051310 metaphase chromosome alignment
IMP
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinet... 		ACCEPT
Summary: TRAPPC12/TRAMM is directly involved in metaphase chromosome alignment/congression.
Reason: Accept as a core moonlighting mitotic process. TRAMM depletion causes noncongressed chromosomes, mitotic arrest, and a phenotype similar to CENP-E depletion.
Supporting Evidence:
PMID:25918224
Depletion of TRAMM resulted in noncongressed chromosomes
PMID:25918224
arrested cells in mitosis
PMID:25918224
TRAMM and CENP-E may act together in chromosome congression
file:human/TRAPPC12/TRAPPC12-uniprot.txt
the recruitment of CENPE to the kinetochores
GO:0090234 regulation of kinetochore assembly
IMP
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinet... 		ACCEPT
Summary: TRAPPC12/TRAMM regulates kinetochore assembly/stability during mitosis.
Reason: Accept as a core moonlighting mitotic process. TRAMM depletion alters kinetochore protein localization and the authors identify TRAMM as a regulator of kinetochore stability.
Supporting Evidence:
PMID:25918224
kinetochore stability and CENP-E recruitment
PMID:25918224
TRAMM affects the localization of some components of the outer layer of the kinetochore
PMID:25918224
small amounts of TRAMM on chromosomes associate with ACA-positive structures representing the kinetochore
file:human/TRAPPC12/TRAPPC12-uniprot.txt
the recruitment of CENPE to the kinetochores
GO:1905342 positive regulation of protein localization to kinetochore
IMP
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinet... 		ACCEPT
Summary: TRAPPC12/TRAMM promotes CENP-E localization to kinetochores.
Reason: Accept as a core moonlighting mitotic process. TRAMM depletion prevents CENP-E recruitment, and phosphomimetic TRAMM recruits more CENP-E to kinetochores than the nonphosphorylatable mutant.
Supporting Evidence:
PMID:25918224
prevented the recruitment of CENP-E to the kinetochore
PMID:25918224
TRAMM-5D was able to recruit more CENP-E to kinetochores
PMID:25918224
TRAMM affects the localization of some components of the outer layer of the kinetochore
file:human/TRAPPC12/TRAPPC12-uniprot.txt
the recruitment of CENPE to the kinetochores
GO:0005829 cytosol
TAS
Reactome:R-HSA-8877475 		ACCEPT
Summary: Cytosol is consistent with TRAPPC12-containing TRAPP trafficking reactions.
Reason: Accept as supported location/context for soluble/peripheral TRAPP complex biology.
Supporting Evidence:
PMID:21525244
endogenous C12 was observed to elute in the same high-molecular-weight pool as TRAPP
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

Interphase TRAPPC12 contributes a TRAPP/TRAPPIII-associated subunit to complex-level RAB1 GEF trafficking between ER, ERGIC, and Golgi. This is the proteostasis-network TRAPP-component role and should be modeled as complex contribution rather than independent GEF activity or COPII coat assembly.

Directly Involved In:
endoplasmic reticulum to Golgi vesicle-mediated transport
Cellular Locations:
cytosol cytoplasm endoplasmic reticulum-Golgi intermediate compartment Golgi apparatus perinuclear region of cytoplasm
In Complex:
TRAPPIII protein complex
Supporting Evidence:
  • 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:27066478
    TRAPP III, which contains core TRAPP plus TrappC8, 11-13
  • PMID:21525244
    C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits
  • PMID:21525244
    These results firmly establish the newly identified proteins as stable TRAPP interactors
  • PMID:21525244
    endogenous C12 was observed to elute in the same high-molecular-weight pool as TRAPP
  • PMID:21525244
    ER-to-Golgi trafficking at a very early stage
  • PMID:21525244
    knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment
  • PMID:21525244
    TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements
  • PMID:21525244
    RNAi against C8, C11, or C12 resulted in Golgi fragmentation
  • PMID:28777934
    Protein transport from the endoplasmic reticulum to and through the Golgi was delayed

Mitotic TRAPPC12/TRAMM functions outside the interphase TRAPP pool to support chromosome congression, kinetochore stability/assembly, and recruitment of CENP-E to kinetochores. This is a direct moonlighting role and is not the PN TRAPP-component propagation target.

Directly Involved In:
metaphase chromosome alignment regulation of kinetochore assembly positive regulation of protein localization to kinetochore
Cellular Locations:
nucleus kinetochore
Supporting Evidence:
  • PMID:25918224
    Depletion of TRAMM resulted in noncongressed chromosomes
  • PMID:25918224
    arrested cells in mitosis
  • PMID:25918224
    Small amounts of TRAMM associated with chromosomes
  • PMID:25918224
    small amounts of TRAMM on chromosomes associate with ACA-positive structures representing the kinetochore
  • PMID:25918224
    TRAMM affects the localization of some components of the outer layer of the kinetochore
  • PMID:25918224
    prevented the recruitment of CENP-E to the kinetochore
  • PMID:25918224
    TRAMM-5D was able to recruit more CENP-E to kinetochores
  • PMID:25918224
    TRAMM appears to have a weak or transient association with kinetochores
  • PMID:25918224
    TRAMM cycles between its role in TRAPP in interphase cells

References

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:0000052
Gene Ontology annotation based on curation of immunofluorescence data
PMID:21525244
C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.
PMID:25918224
TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, and CENP-E recruitment.
PMID:27066478
TRAPP Complexes in Secretion and Autophagy.
PMID:32296183
A reference map of the human binary protein interactome.
Reactome:R-HSA-8877475
TRAPPC complexes exchange GTP for GDP on RAB1
PMID:28777934
Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction.
file:human/TRAPPC12/TRAPPC12-uniprot.txt
UniProtKB record for TRAPPC12

Suggested Questions for Experts

Q: Should TRAPPC12/TRAMM be represented in GO-CAM as two separable functional contexts, interphase TRAPP trafficking and mitotic kinetochore/CENP-E recruitment?

Suggested experts: GO transport editors, GO cell-cycle editors, Reactome TRAPP curators

Q: Should generic protein binding annotations for TRAPPC12-CENP-E and TRAPPC12-TRAPP interactions be replaced by more informative kinetochore-localization and TRAPP-complex annotations?

Suggested experts: GO molecular function editors, GO cell-cycle editors

Q: Does direct evidence support a TRAPPC12-specific autophagy process annotation, or should PN autophagy context remain limited to TRAPPIII/TRAPP complex membership?

Suggested experts: GO autophagy editors, TRAPP/autophagy domain experts

Suggested Experiments

Experiment: Use synchronized cells with TRAPPC12 knockdown/rescue and phosphosite mutants to measure TRAPP complex association, ER-Golgi cargo transport, Golgi morphology, CENP-E kinetochore recruitment, and chromosome congression in matched assays.

Hypothesis: TRAPPC12 switches between an interphase TRAPP trafficking role and a mitotic kinetochore/CENP-E recruitment role controlled by phosphorylation and cell-cycle state.

Type: dual trafficking and mitosis rescue assay

Experiment: Reconstitute TRAPPC12-containing TRAPPIII and measure RAB1 exchange plus TRAPPC12 release or altered association after mitotic phosphorylation mimics.

Hypothesis: TRAPPC12 contributes to complex-level RAB1 GEF trafficking while phosphorylation changes its TRAPP association during mitosis.

Type: complex reconstitution and RAB1 GEF assay

Experiment: Test whether TRAPPC12 depletion affects ATG9 cycling or early autophagy markers independently of ER-Golgi trafficking and mitotic arrest.

Hypothesis: If TRAPPC12 has a direct autophagy role, autophagy-initiation defects should be separable from its secretory and mitotic phenotypes.

Type: autophagy trafficking assay

📚 Additional Documentation

Notes

(TRAPPC12-notes.md)

TRAPPC12 review notes

TRAPPC12, also called TRAMM/TTC-15, has two directly supported functional tracks: TRAPP-mediated membrane traffic and a moonlighting mitotic kinetochore role. Scrivens et al. identify TTC-15 as TRAPPC12 and state that C11/C12 are bona fide TRAPP components involved in early ER-to-Golgi trafficking [PMID:21525244 "TTC-15 (now designated TRAPPC12)" and "ER-to-Golgi trafficking at a very early stage"].

TRAPP membership is directly supported by TRAPP purifications and coimmunoprecipitation. TRAPPC11 and TRAPPC12 interact with each other and known TRAPP subunits, and newly identified proteins are stable TRAPP interactors [PMID:21525244 "C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits" and "These results firmly establish the newly identified proteins as stable TRAPP interactors"].

TRAPPC12 localizes in TRAPP/early secretory contexts. Endogenous C12 elutes in a high-molecular-weight TRAPP pool and a second smaller pool, consistent with the dual biology later described for TRAMM [PMID:21525244 "endogenous C12 was observed to elute in the same high-molecular-weight pool as TRAPP" and PMID:25918224 "TRAMM cycles between its role in TRAPP in interphase cells, and its newly identified roles during mitosis"].

TRAPPC12 supports ER-to-ERGIC/Golgi traffic rather than COPII coat assembly per se. C12 knockdown causes fragmented Golgi, C11/C12 knockdown arrests cargo in a BFA-resistant ERGIC-associated compartment, and the authors model TRAPP function at ER exit or peripheral ERGIC elements [PMID:21525244 "RNAi against C8, C11, or C12 resulted in Golgi fragmentation", "knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment", and "TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements"].

The PN TRAPP leaf is autophagy-contextual but maps to TRAPP complex membership. For TRAPPC12, I am not adding a direct autophagy annotation: the direct seeded records support TRAPP/TRAPPIII membership and early secretory trafficking, while autophagy is represented by TRAPPIII/RAB1 context only [PMID:27066478 "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"].

The mitosis paper provides direct, full-text support for TRAPPC12/TRAMM nuclear/kinetochore and chromosome-congression annotations. TRAMM depletion causes noncongressed chromosomes and mitotic arrest, TRAMM weakly associates with chromosomes/kinetochores, and TRAMM regulates CENP-E recruitment to kinetochores [PMID:25918224 "Depletion of TRAMM resulted in noncongressed chromosomes", "Small amounts of TRAMM associated with chromosomes", and "prevented the recruitment of CENP-E to the kinetochore"].

The CENP-E interaction is real but the generic GO term protein binding is not an informative representation of TRAPPC12 function. The better GO representation is positive regulation of protein localization to kinetochore, regulation of kinetochore assembly, and metaphase chromosome alignment [PMID:25918224 "TRAMM affects the localization of some components of the outer layer of the kinetochore" and "TRAMM was able to recruit more CENP-E to kinetochores"].

The TRAPPC12 disease paper is cached as abstract-only. It supports Golgi dysfunction and delayed ER-to-Golgi/Golgi transport, but I am using it only as secondary support [PMID:28777934 "Fibroblasts derived from all three individuals showed a fragmented Golgi" and "Protein transport from the endoplasmic reticulum to and through the Golgi was delayed"].

The fetched PANTHER family metadata for PTHR21581 is labeled "D-alanyl-D-alanine Carboxypeptidase", which does not match TRAPPC12/TRAMM biology. I am not using that artifact as functional evidence for this review.

Falcon deep research was requested with just deep-research-falcon human TRAPPC12, but the provider timed out after 600 seconds and no TRAPPC12-deep-research-falcon.md file was produced. I am completing the review using the cached primary literature, UniProt record, GOA seed, and Reactome context described above.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: the prior wording framed TRAPPC12 in the Proteostasis Network TRAPP bucket, where its shared gene-level semantics are TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking, not a direct TRAPPC12-specific autophagy annotation.

Pn Notes

(TRAPPC12-pn-notes.md)

TRAPPC12 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q8WVT3
  • 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: TRAPPC12/TRAMM/TTC-15 is a moonlighting metazoan TRAPP/TRAPPIII-associated protein. In interphase it participates in TRAPP-dependent early secretory traffic between ER, ERGIC, and Golgi. During mitosis it leaves the TRAPP context and supports chromosome congression, kinetochore stability, and CENP-E recruitment. Its shared cellular roles are TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1 trafficking; direct TRAPPC12-specific autophagy evidence is limited.
  • Existing/core annotation action counts: ACCEPT: 18; KEEP_AS_NON_CORE: 1; MARK_AS_OVER_ANNOTATED: 3; MODIFY: 3

PN Consistency Summary

  • Consistency: Consistent. Notes and YAML agree on two directly-supported tracks — interphase TRAPP/TRAPPIII early-secretory traffic, and a moonlighting mitotic kinetochore/CENP-E role (PMID:25918224) — and explicitly decline a TRAPPC12-specific autophagy annotation ("I am not adding a direct autophagy annotation… autophagy is represented by TRAPPIII/RAB1 context only"). This matches the PN complex-only mapping. No contradictions.
  • PN story / NEW pressure: PN restricts to GO:0030008 membership; unlike TRAPPC11, TRAPPC12 has no direct gene-specific autophagy evidence, so the review correctly does not mint an autophagy BP (proposed_new_terms: []). GO:0030008 is verified real and already in GOA. The mitotic moonlighting functions (GO:0051310, GO:0090234, GO:1905342) are outside the PN scope and correctly flagged as non-PN-propagation targets. Conclude: already captured; no NEW warranted — good asymmetry vs TRAPPC11.
  • Evidence alignment: Overlap on TRAPP: PN cites PMID:27066478 + Frontiers review = review core. Review enriches with PMID:21525244 (TRAPP ID), 28777934 (CDG/encephalopathy), 25918224 (mitosis) — none in PN, all consistent. (Notes flag a spurious PANTHER PTHR21581 "D-Ala-D-Ala carboxypeptidase" artifact, correctly not used.)
  • Verdict: Fully consistent; correctly conservative on autophagy. No edits needed.

Full Consistency Review

  • UniProt: Q8WVT3 (TRAMM/TTC-15) · 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: Consistent. Notes and YAML agree on two directly-supported tracks — interphase TRAPP/TRAPPIII early-secretory traffic, and a moonlighting mitotic kinetochore/CENP-E role (PMID:25918224) — and explicitly decline a TRAPPC12-specific autophagy annotation ("I am not adding a direct autophagy annotation… autophagy is represented by TRAPPIII/RAB1 context only"). This matches the PN complex-only mapping. No contradictions.
  • PN story / NEW pressure: PN restricts to GO:0030008 membership; unlike TRAPPC11, TRAPPC12 has no direct gene-specific autophagy evidence, so the review correctly does not mint an autophagy BP (proposed_new_terms: []). GO:0030008 is verified real and already in GOA. The mitotic moonlighting functions (GO:0051310, GO:0090234, GO:1905342) are outside the PN scope and correctly flagged as non-PN-propagation targets. Conclude: already captured; no NEW warranted — good asymmetry vs TRAPPC11.
  • Mapping strategy: Gene does not change the node (GO:0030008 correct, macroautophagy correctly held at context_only). The mitotic functions are appropriately excluded from the shared TRAPP bucket.
  • Evidence alignment: Overlap on TRAPP: PN cites PMID:27066478 + Frontiers review = review core. Review enriches with PMID:21525244 (TRAPP ID), 28777934 (CDG/encephalopathy), 25918224 (mitosis) — none in PN, all consistent. (Notes flag a spurious PANTHER PTHR21581 "D-Ala-D-Ala carboxypeptidase" artifact, correctly not used.)
  • Verdict: Fully consistent; correctly conservative on autophagy. No edits needed.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/TRAPPC12/TRAPPC12-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: Q8WVT3
  • In branches: ALP
  • Notes: TRAPP III complex, specific 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: Q8WVT3
gene_symbol: TRAPPC12
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  TRAPPC12/TRAMM/TTC-15 is a moonlighting metazoan TRAPP/TRAPPIII-associated protein. In interphase it
  participates in TRAPP-dependent early secretory traffic between ER, ERGIC, and Golgi. During mitosis
  it leaves the TRAPP context and supports chromosome congression, kinetochore stability, and CENP-E
  recruitment. Its shared cellular roles are TRAPP/TRAPPII/TRAPPIII complex membership and TRAPP/RAB1
  trafficking; direct TRAPPC12-specific autophagy evidence is limited.
existing_annotations:
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Golgi apparatus localization/activity context is supported for 
      TRAPPC12/TRAPP trafficking.
    action: ACCEPT
    reason: Accept as supported location/context. TRAPPC12 is mainly observed in 
      Golgi/perinuclear TRAPP context, and TRAPPC12 disease fibroblasts show rescued 
      Golgi fragmentation and delayed ER-to-Golgi/Golgi transport.
    additional_reference_ids:
    - PMID:21525244
    - PMID:28777934
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - &id004
      reference_id: PMID:21525244
      supporting_text: C12 is largely found in punctae throughout the cell
    - &id003
      reference_id: PMID:21525244
      supporting_text: highly punctate with an obvious concentration of the punctae in 
        the perinuclear region
    - &id015
      reference_id: PMID:21525244
      supporting_text: RNAi against C8, C11, or C12 resulted in Golgi fragmentation
    - &id016
      reference_id: PMID:28777934
      supporting_text: Fibroblasts derived from all three individuals showed a 
        fragmented Golgi
    - &id007
      reference_id: PMID:28777934
      supporting_text: Protein transport from the endoplasmic reticulum to and through 
        the Golgi was delayed
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: TRAPPC12 is a mammalian TRAPP complex component.
    action: ACCEPT
    reason: Accept as core cellular-component membership. TRAPPC12/TTC-15 is identified 
      as a stable mammalian TRAPP interactor, and UniProt describes it as a component of
      the multisubunit TRAPP complex.
    additional_reference_ids:
    - PMID:21525244
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    - PMID:25918224
    supported_by:
    - &id022
      reference_id: PMID:21525244
      supporting_text: TTC-15 (now designated TRAPPC12)
    - &id001
      reference_id: PMID:21525244
      supporting_text: C4orf41 and TTC-15 interact both with each other and with 
        previously characterized TRAPP subunits
    - &id002
      reference_id: PMID:21525244
      supporting_text: These results firmly establish the newly identified proteins as 
        stable TRAPP interactors
    - &id023
      reference_id: PMID:21525244
      supporting_text: endogenous C12 was observed to elute in the same 
        high-molecular-weight pool as TRAPP
    - &id024
      reference_id: file:human/TRAPPC12/TRAPPC12-uniprot.txt
      supporting_text: Component of the multisubunit TRAPP (transport protein
    - &id025
      reference_id: PMID:25918224
      supporting_text: TRAMM cycles between its role in TRAPP in interphase cells
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear localization is supported for the mitotic TRAMM/TRAPPC12 branch.
    action: ACCEPT
    reason: Accept as a supported location for the moonlighting mitotic role. TRAMM 
      cofractionates with a nuclear marker, associates weakly with mitotic 
      chromosomes/kinetochores, and UniProt cites nuclear localization from 
      PMID:25918224.
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - &id011
      reference_id: PMID:25918224
      supporting_text: cellular fractionation indicated that a small but reproducible 
        amount of TRAMM cofractionated with a nuclear marker
    - &id012
      reference_id: PMID:25918224
      supporting_text: Small amounts of TRAMM associated with chromosomes
    - &id013
      reference_id: PMID:25918224
      supporting_text: small amounts of TRAMM on chromosomes associate with ACA-positive
        structures representing the kinetochore
    - &id014
      reference_id: file:human/TRAPPC12/TRAPPC12-uniprot.txt
      supporting_text: Nucleus {ECO:0000269|PubMed:25918224}
- term:
    id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: ERGIC localization/colocalization is supported for early TRAPP secretory 
      traffic.
    action: ACCEPT
    reason: Accept as supported location/context. TRAPPC12/C12 is part of the TRAPP 
      early secretory pathway, and C11/C12 depletion arrests VSV-G cargo in a 
      BFA-resistant ERGIC-associated compartment.
    additional_reference_ids:
    - PMID:21525244
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - &id005
      reference_id: PMID:21525244
      supporting_text: knockdowns of either C11 or C12 arrest a cargo protein in a 
        BFA-resistant compartment
    - &id006
      reference_id: PMID:21525244
      supporting_text: TRAPP functions either at ER exit sites or at peripheral ERGIC 
        (BFA-resistant) elements
    - &id019
      reference_id: file:human/TRAPPC12/TRAPPC12-uniprot.txt
      supporting_text: Endoplasmic reticulum-Golgi intermediate
- 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 TRAPPC12 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. TRAPPC12 interactions are better represented as 
      TRAPP/TRAPPIII complex membership or as CENP-E recruitment to kinetochore, not as 
      generic protein binding.
    additional_reference_ids:
    - PMID:21525244
    - PMID:25918224
    - PMID:32296183
    supported_by:
    - *id001
    - *id002
    - &id017
      reference_id: PMID:25918224
      supporting_text: prevented the recruitment of CENP-E to the kinetochore
    - &id018
      reference_id: PMID:25918224
      supporting_text: TRAMM-5D was able to recruit more CENP-E to kinetochores
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: located_in
  review:
    summary: Cytoplasm is a broad but reasonable location for TRAPPC12 
      soluble/peripheral TRAPP biology.
    action: ACCEPT
    reason: Accept as broad supported location/context. TRAPPC12 has 
      cytoplasmic/perinuclear/Golgi pools in early secretory traffic and a distinct 
      mitotic pool.
    additional_reference_ids:
    - PMID:21525244
    - PMID:25918224
    - Reactome:R-HSA-8877475
    supported_by:
    - *id003
    - *id004
    - reference_id: PMID:25918224
      supporting_text: the supernatant was kept as the cytoplasmic fraction
    - &id028
      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:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: TRAPPC12 participates in early secretory ER-to-ERGIC/Golgi transport 
      through TRAPP/TRAPPIII.
    action: ACCEPT
    reason: Accept as a core process. Direct TRAPPC12 evidence supports early 
      ER-to-Golgi trafficking, ERGIC cargo arrest, Golgi fragmentation on depletion, and
      delayed ER-to-Golgi/Golgi transport in patient fibroblasts.
    additional_reference_ids:
    - PMID:21525244
    - PMID:28777934
    - Reactome:R-HSA-8877475
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - &id008
      reference_id: PMID:21525244
      supporting_text: ER-to-Golgi trafficking at a very early stage
    - *id005
    - *id006
    - &id020
      reference_id: PMID:21525244
      supporting_text: These results imply that the three novel TRAPP-associated 
        proteins function in the early secretory pathway
    - *id007
    - &id021
      reference_id: file:human/TRAPPC12/TRAPPC12-uniprot.txt
      supporting_text: endoplasmic reticulum to Golgi apparatus trafficking at a very 
        early
    - &id009
      reference_id: Reactome:R-HSA-8877475
      supporting_text: RAB1 is involved in COPII-mediated anterograde traffic from the 
        endoplasmic reticulum to the ERGIC
- term:
    id: GO:0048208
    label: COPII vesicle coat assembly
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The COPII coat assembly annotation captures early secretory context but 
      overstates TRAPPC12 as a coat-assembly factor.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC12 evidence supports
      early ER/ERGIC/Golgi trafficking in COPII-associated anterograde traffic, not 
      direct assembly of the COPII vesicle coat.
    proposed_replacement_terms:
    - &id010
      id: GO:0006888
      label: endoplasmic reticulum to Golgi vesicle-mediated transport
    additional_reference_ids:
    - PMID:21525244
    - PMID:28777934
    - Reactome:R-HSA-8877475
    supported_by:
    - *id008
    - *id005
    - *id006
    - *id007
    - *id009
- term:
    id: GO:0099022
    label: obsolete vesicle tethering
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: involved_in
  review:
    summary: The obsolete vesicle-tethering annotation should not be retained as-is.
    action: MODIFY
    reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported 
      TRAPPC12/TRAPP process. Mammalian TRAPP tethering remains unresolved and this GO 
      term is obsolete.
    proposed_replacement_terms:
    - *id010
    additional_reference_ids:
    - PMID:27066478
    - PMID:21525244
    - PMID:28777934
    supported_by:
    - reference_id: PMID:27066478
      supporting_text: evidence that any TRAPP complex acts as a membrane tether is 
        currently inconclusive
    - *id008
    - *id006
    - *id007
- term:
    id: GO:1990072
    label: TRAPPIII protein complex
  evidence_type: NAS
  original_reference_id: PMID:27066478
  qualifier: part_of
  review:
    summary: TRAPPC12 is modeled as a mammalian TRAPPIII-associated subunit.
    action: ACCEPT
    reason: Accept as core complex membership in the PN TRAPP bucket. The review 
      literature assigns TRAPPC12 to mammalian TRAPPIII, and Reactome models TRAPPCIII 
      in RAB1/autophagy context.
    additional_reference_ids:
    - PMID:27066478
    - PMID:21525244
    - Reactome:R-HSA-8877475
    supported_by:
    - &id029
      reference_id: PMID:27066478
      supporting_text: TRAPP III, which contains core TRAPP plus TrappC8, 11-13
    - *id001
    - *id002
    - 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)
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Nucleoplasm is more specific than the accessible TRAMM/TRAPPC12 evidence 
      supports.
    action: MODIFY
    reason: Modify to nucleus. The seeded HPA-derived row may reflect nuclear 
      immunofluorescence, but the accessible full-text evidence supports 
      nuclear/chromosome/kinetochore association rather than nucleoplasm specifically.
    proposed_replacement_terms:
    - id: GO:0005634
      label: nucleus
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id011
    - *id012
    - *id013
    - *id014
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Golgi apparatus localization/activity context is supported for 
      TRAPPC12/TRAPP trafficking.
    action: ACCEPT
    reason: Accept as supported location/context. TRAPPC12 is mainly observed in 
      Golgi/perinuclear TRAPP context, and TRAPPC12 disease fibroblasts show rescued 
      Golgi fragmentation and delayed ER-to-Golgi/Golgi transport.
    additional_reference_ids:
    - PMID:21525244
    - PMID:28777934
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id004
    - *id003
    - *id015
    - *id016
    - *id007
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21525244
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC12 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. TRAPPC12 interactions are better represented as 
      TRAPP/TRAPPIII complex membership or as CENP-E recruitment to kinetochore, not as 
      generic protein binding.
    additional_reference_ids:
    - PMID:21525244
    - PMID:25918224
    - PMID:32296183
    supported_by:
    - *id001
    - *id002
    - *id017
    - *id018
- term:
    id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: colocalizes_with
  review:
    summary: ERGIC localization/colocalization is supported for early TRAPP secretory 
      traffic.
    action: ACCEPT
    reason: Accept as supported location/context. TRAPPC12/C12 is part of the TRAPP 
      early secretory pathway, and C11/C12 depletion arrests VSV-G cargo in a 
      BFA-resistant ERGIC-associated compartment.
    additional_reference_ids:
    - PMID:21525244
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id005
    - *id006
    - *id019
- term:
    id: GO:0006888
    label: endoplasmic reticulum to Golgi vesicle-mediated transport
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: involved_in
  review:
    summary: TRAPPC12 participates in early secretory ER-to-ERGIC/Golgi transport 
      through TRAPP/TRAPPIII.
    action: ACCEPT
    reason: Accept as a core process. Direct TRAPPC12 evidence supports early 
      ER-to-Golgi trafficking, ERGIC cargo arrest, Golgi fragmentation on depletion, and
      delayed ER-to-Golgi/Golgi transport in patient fibroblasts.
    additional_reference_ids:
    - PMID:21525244
    - PMID:28777934
    - Reactome:R-HSA-8877475
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id008
    - *id005
    - *id006
    - *id020
    - *id007
    - *id021
    - *id009
- term:
    id: GO:0007030
    label: Golgi organization
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: involved_in
  review:
    summary: Golgi organization is a direct TRAPPC12-depletion/disease phenotype but is 
      secondary to early secretory trafficking.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. Golgi fragmentation is a useful readout of TRAPPC12/TRAPP 
      disruption and is disease-relevant, while the core process is ER-to-ERGIC/Golgi 
      trafficking.
    additional_reference_ids:
    - PMID:21525244
    - PMID:28777934
    supported_by:
    - *id015
    - *id016
    - *id020
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IMP
  original_reference_id: PMID:21525244
  qualifier: colocalizes_with
  review:
    summary: Perinuclear cytoplasmic localization is supported for interphase 
      TRAPPC12/Golgi puncta.
    action: ACCEPT
    reason: Accept as a supported location for the interphase trafficking pool of 
      TRAPPC12.
    additional_reference_ids:
    - PMID:21525244
    - PMID:25918224
    supported_by:
    - *id003
    - *id004
    - reference_id: PMID:25918224
      supporting_text: TRAMM is largely localized to a perinuclear region representing 
        the Golgi
- term:
    id: GO:0030008
    label: TRAPP complex
  evidence_type: IDA
  original_reference_id: PMID:21525244
  qualifier: part_of
  review:
    summary: TRAPPC12 is a mammalian TRAPP complex component.
    action: ACCEPT
    reason: Accept as core cellular-component membership. TRAPPC12/TTC-15 is identified 
      as a stable mammalian TRAPP interactor, and UniProt describes it as a component of
      the multisubunit TRAPP complex.
    additional_reference_ids:
    - PMID:21525244
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    - PMID:25918224
    supported_by:
    - *id022
    - *id001
    - *id002
    - *id023
    - *id024
    - *id025
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IDA
  original_reference_id: PMID:25918224
  qualifier: located_in
  review:
    summary: Kinetochore localization is weak/transient but directly supported for 
      mitotic TRAMM/TRAPPC12.
    action: ACCEPT
    reason: Accept as supported. The full-text paper shows small amounts of TRAMM on 
      chromosomes associated with ACA-positive kinetochore structures and frames this as
      a weak/transient kinetochore association.
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id012
    - *id013
    - &id032
      reference_id: PMID:25918224
      supporting_text: TRAMM appears to have a weak or transient association with 
        kinetochores
    - &id026
      reference_id: file:human/TRAPPC12/TRAPPC12-uniprot.txt
      supporting_text: the recruitment of CENPE to the kinetochores
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25918224
  qualifier: enables
  review:
    summary: Generic protein binding is not informative for TRAPPC12 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated. TRAPPC12 interactions are better represented as 
      TRAPP/TRAPPIII complex membership or as CENP-E recruitment to kinetochore, not as 
      generic protein binding.
    additional_reference_ids:
    - PMID:21525244
    - PMID:25918224
    - PMID:32296183
    supported_by:
    - *id001
    - *id002
    - *id017
    - *id018
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25918224
  qualifier: located_in
  review:
    summary: Nuclear localization is supported for the mitotic TRAMM/TRAPPC12 branch.
    action: ACCEPT
    reason: Accept as a supported location for the moonlighting mitotic role. TRAMM 
      cofractionates with a nuclear marker, associates weakly with mitotic 
      chromosomes/kinetochores, and UniProt cites nuclear localization from 
      PMID:25918224.
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id011
    - *id012
    - *id013
    - *id014
- term:
    id: GO:0051310
    label: metaphase chromosome alignment
  evidence_type: IMP
  original_reference_id: PMID:25918224
  qualifier: involved_in
  review:
    summary: TRAPPC12/TRAMM is directly involved in metaphase chromosome 
      alignment/congression.
    action: ACCEPT
    reason: Accept as a core moonlighting mitotic process. TRAMM depletion causes 
      noncongressed chromosomes, mitotic arrest, and a phenotype similar to CENP-E 
      depletion.
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - &id030
      reference_id: PMID:25918224
      supporting_text: Depletion of TRAMM resulted in noncongressed chromosomes
    - &id031
      reference_id: PMID:25918224
      supporting_text: arrested cells in mitosis
    - reference_id: PMID:25918224
      supporting_text: TRAMM and CENP-E may act together in chromosome congression
    - *id026
- term:
    id: GO:0090234
    label: regulation of kinetochore assembly
  evidence_type: IMP
  original_reference_id: PMID:25918224
  qualifier: involved_in
  review:
    summary: TRAPPC12/TRAMM regulates kinetochore assembly/stability during mitosis.
    action: ACCEPT
    reason: Accept as a core moonlighting mitotic process. TRAMM depletion alters 
      kinetochore protein localization and the authors identify TRAMM as a regulator of 
      kinetochore stability.
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - reference_id: PMID:25918224
      supporting_text: kinetochore stability and CENP-E recruitment
    - &id027
      reference_id: PMID:25918224
      supporting_text: TRAMM affects the localization of some components of the outer 
        layer of the kinetochore
    - *id013
    - *id026
- term:
    id: GO:1905342
    label: positive regulation of protein localization to kinetochore
  evidence_type: IMP
  original_reference_id: PMID:25918224
  qualifier: involved_in
  review:
    summary: TRAPPC12/TRAMM promotes CENP-E localization to kinetochores.
    action: ACCEPT
    reason: Accept as a core moonlighting mitotic process. TRAMM depletion prevents 
      CENP-E recruitment, and phosphomimetic TRAMM recruits more CENP-E to kinetochores 
      than the nonphosphorylatable mutant.
    additional_reference_ids:
    - PMID:25918224
    - file:human/TRAPPC12/TRAPPC12-uniprot.txt
    supported_by:
    - *id017
    - *id018
    - *id027
    - *id026
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8877475
  qualifier: located_in
  review:
    summary: Cytosol is consistent with TRAPPC12-containing TRAPP trafficking reactions.
    action: ACCEPT
    reason: Accept as supported location/context for soluble/peripheral TRAPP complex 
      biology.
    additional_reference_ids:
    - PMID:21525244
    - Reactome:R-HSA-8877475
    supported_by:
    - *id023
    - *id028
references:
- 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:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:21525244
  title: C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage
    in ER-to-Golgi trafficking.
  findings: []
- id: PMID:25918224
  title: TRAMM/TrappC12 plays a role in chromosome congression, kinetochore stability, 
    and CENP-E recruitment.
  findings: []
- id: PMID:27066478
  title: TRAPP Complexes in Secretion and Autophagy.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: Reactome:R-HSA-8877475
  title: TRAPPC complexes exchange GTP for GDP on RAB1
  findings: []
- id: PMID:28777934
  title: Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and 
    Golgi Dysfunction.
  findings: []
- id: file:human/TRAPPC12/TRAPPC12-uniprot.txt
  title: UniProtKB record for TRAPPC12
  findings: []
core_functions:
- contributes_to_molecular_function:
    id: GO:0005085
    label: guanyl-nucleotide exchange factor activity
  in_complex:
    id: GO:1990072
    label: TRAPPIII protein complex
  description: Interphase TRAPPC12 contributes a TRAPP/TRAPPIII-associated subunit to 
    complex-level RAB1 GEF trafficking between ER, ERGIC, and Golgi. This is the 
    proteostasis-network TRAPP-component role and should be modeled as complex 
    contribution rather than independent GEF activity or COPII coat assembly.
  directly_involved_in:
  - *id010
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  - id: GO:0005794
    label: Golgi apparatus
  - id: GO:0048471
    label: perinuclear region of cytoplasm
  supported_by:
  - *id028
  - *id029
  - *id001
  - *id002
  - *id023
  - *id008
  - *id005
  - *id006
  - *id015
  - *id007
- description: Mitotic TRAPPC12/TRAMM functions outside the interphase TRAPP pool to 
    support chromosome congression, kinetochore stability/assembly, and recruitment of 
    CENP-E to kinetochores. This is a direct moonlighting role and is not the PN 
    TRAPP-component propagation target.
  directly_involved_in:
  - id: GO:0051310
    label: metaphase chromosome alignment
  - id: GO:0090234
    label: regulation of kinetochore assembly
  - id: GO:1905342
    label: positive regulation of protein localization to kinetochore
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0000776
    label: kinetochore
  supported_by:
  - *id030
  - *id031
  - *id012
  - *id013
  - *id027
  - *id017
  - *id018
  - *id032
  - *id025
proposed_new_terms: []
suggested_questions:
- question: Should TRAPPC12/TRAMM be represented in GO-CAM as two separable functional 
    contexts, interphase TRAPP trafficking and mitotic kinetochore/CENP-E recruitment?
  experts:
  - GO transport editors
  - GO cell-cycle editors
  - Reactome TRAPP curators
- question: Should generic protein binding annotations for TRAPPC12-CENP-E and 
    TRAPPC12-TRAPP interactions be replaced by more informative kinetochore-localization
    and TRAPP-complex annotations?
  experts:
  - GO molecular function editors
  - GO cell-cycle editors
- question: Does direct evidence support a TRAPPC12-specific autophagy process 
    annotation, or should PN autophagy context remain limited to TRAPPIII/TRAPP complex 
    membership?
  experts:
  - GO autophagy editors
  - TRAPP/autophagy domain experts
suggested_experiments:
- description: Use synchronized cells with TRAPPC12 knockdown/rescue and phosphosite 
    mutants to measure TRAPP complex association, ER-Golgi cargo transport, Golgi 
    morphology, CENP-E kinetochore recruitment, and chromosome congression in matched 
    assays.
  experiment_type: dual trafficking and mitosis rescue assay
  hypothesis: TRAPPC12 switches between an interphase TRAPP trafficking role and a 
    mitotic kinetochore/CENP-E recruitment role controlled by phosphorylation and 
    cell-cycle state.
- description: Reconstitute TRAPPC12-containing TRAPPIII and measure RAB1 exchange plus 
    TRAPPC12 release or altered association after mitotic phosphorylation mimics.
  experiment_type: complex reconstitution and RAB1 GEF assay
  hypothesis: TRAPPC12 contributes to complex-level RAB1 GEF trafficking while 
    phosphorylation changes its TRAPP association during mitosis.
- description: Test whether TRAPPC12 depletion affects ATG9 cycling or early autophagy 
    markers independently of ER-Golgi trafficking and mitotic arrest.
  experiment_type: autophagy trafficking assay
  hypothesis: If TRAPPC12 has a direct autophagy role, autophagy-initiation defects 
    should be separable from its secretory and mitotic phenotypes.