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.
| 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. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport 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. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport 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 |
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Download this section (compressed HTML)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
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
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