TRAPPC11 (C4orf41/Gryzun) is a metazoan TRAPP/TRAPPIII-associated subunit. It stabilizes mammalian TRAPP architecture and contributes to early secretory pathway trafficking between the ER, ERGIC, and Golgi. Patient-cell evidence also supports a TRAPPC11 role in starvation-induced autophagic flux and autophagosome sealing. As a TRAPPIII-associated subunit, TRAPPC11 is connected to TRAPP complex membership, complex-level RAB1 GEF activity, ER-to-Golgi transport, TRAPP complex stability, and autophagosome maturation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology. Reason: Accept as a supported cellular location. UniProt maps TRAPPC11 to the Golgi apparatus with PMID:27862579 support, and the CDG abstract reports delayed Golgi vesicular transport caused by TRAPPC11 mutation. Supporting Evidence: file:human/TRAPPC11/TRAPPC11-uniprot.txt Golgi apparatus {ECO:0000269|PubMed:27862579} PMID:27862579 delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex PMID:21525244 RNAi against C8, C11, or C12 resulted in Golgi fragmentation |
| GO:0005737 cytoplasm | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | ACCEPT | Summary: Cytoplasm is a broad but reasonable location for soluble/peripheral TRAPP complex biology. Reason: Accept as a broad supported location/context. TRAPP subunits have large soluble pools and function on early secretory pathway membranes; the more specific cytosol/Golgi locations are captured elsewhere. Supporting Evidence: PMID:21525244 Localization of subunits by fluorescence microscopy has proven difficult due to the large soluble pools of the proteins PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements 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: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII. Reason: Accept as a core process. TRAPPC11 was identified as a mammalian TRAPP component with C11-specific ER-to-ERGIC traffic evidence, and independent secretory-screen evidence shows human Gryzun/C4orf41 knockdown blocks Golgi exit. Supporting Evidence: PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment 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:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit file:human/TRAPPC11/TRAPPC11-uniprot.txt Involved in endoplasmic reticulum to Golgi apparatus 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 TRAPPC11 as a coat-assembly factor. Reason: Modify to ER-to-Golgi vesicle-mediated transport. TRAPPC11 evidence supports early ER/ERGIC/Golgi trafficking in COPII-associated anterograde traffic, not assembly of the COPII vesicle coat. Proposed replacements: endoplasmic reticulum to Golgi vesicle-mediated transport Supporting Evidence: PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit 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 TRAPPC11/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 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit |
| GO:1990072 TRAPPIII protein complex | NAS PMID:27066478 TRAPP Complexes in Secretion and Autophagy. | ACCEPT | Summary: TRAPPC11 is modeled as a mammalian TRAPPIII-associated subunit. Reason: Accept as core complex membership. TRAPPC11 is a metazoan TRAPP component assigned to mammalian TRAPP III in the review literature and independently described as a TRAPPIII subunit in the TRAPPC11-CDG abstract. Supporting Evidence: PMID:27066478 TRAPP III, which contains core TRAPP plus TrappC8, 11-13 PMID:27066478 TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13 PMID:27862579 delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex PMID:21525244 C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits Reactome:R-HSA-8877475 RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS) |
| GO:0045054 constitutive secretory pathway | IMP PMID:19942856 A genome-wide RNA interference screen identifies two novel c... | ACCEPT | Summary: TRAPPC11 is directly supported as an early secretory pathway factor. Reason: Accept as a supported core process at broad pathway level. The RNAi secretory screen shows human C4orf41/Gryzun blocks Golgi exit, and the TRAPP component paper places TRAPPC11 in early ER/ERGIC/Golgi trafficking. Supporting Evidence: PMID:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment PMID:21525244 These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway file:human/TRAPPC11/TRAPPC11-uniprot.txt Involved in endoplasmic reticulum to Golgi apparatus |
| 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 TRAPPC11 function. Reason: Mark as over-annotated. The interaction evidence is better represented as TRAPP/TRAPPIII complex membership and TRAPP architecture/stability, not a generic protein binding molecular function. 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:21525244 we report two novel TRAPP proteins, C4orf41/Gryzun (now designated TRAPPC11) and TTC-15 (now designated TRAPPC12) PMID:27066478 TrappC11, which is distantly related to Trs130/TrappC10, and TrappC12, were identified based on their co-fractionation with TRAPP and effect of their depletion on ER-to-Golgi transport |
| 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: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII. Reason: Accept as a core process. TRAPPC11 was identified as a mammalian TRAPP component with C11-specific ER-to-ERGIC traffic evidence, and independent secretory-screen evidence shows human Gryzun/C4orf41 knockdown blocks Golgi exit. Supporting Evidence: PMID:21525244 Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment 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:19942856 RNAi of human Gryzun (C4orf41) blocks Golgi exit file:human/TRAPPC11/TRAPPC11-uniprot.txt Involved in endoplasmic reticulum to Golgi apparatus 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 TRAPPC11-depletion phenotype but is secondary to early secretory trafficking. Reason: Keep as non-core. Golgi fragmentation is a useful readout of TRAPPC11/TRAPP disruption, while the core process is ER-to-ERGIC/Golgi trafficking and TRAPP complex stability. Supporting Evidence: PMID:21525244 RNAi against C8, C11, or C12 resulted in Golgi fragmentation PMID:21525244 These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway |
| GO:0030008 TRAPP complex | IMP PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol... | ACCEPT | Summary: TRAPPC11 is a mammalian TRAPP complex component. Reason: Accept as core cellular-component membership. TAP purification and coimmunoprecipitation identify C4orf41/TRAPPC11 as stably associated with mammalian TRAPP subunits. 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:21525244 we report two novel TRAPP proteins, C4orf41/Gryzun (now designated TRAPPC11) and TTC-15 (now designated TRAPPC12) PMID:27066478 TrappC11, which is distantly related to Trs130/TrappC10, and TrappC12, were identified based on their co-fractionation with TRAPP and effect of their depletion on ER-to-Golgi transport file:human/TRAPPC11/TRAPPC11-uniprot.txt Component of the multisubunit TRAPP (transport protein |
| GO:0061635 regulation of protein complex stability | IMP PMID:21525244 C4orf41 and TTC-15 are mammalian TRAPP components with a rol... | ACCEPT | Summary: TRAPPC11 supports mammalian TRAPP complex stability. Reason: Accept as a supported core process/function of TRAPPC11 within the TRAPP complex. C11 depletion partially disassembles the complex and the authors conclude that C11 stabilizes mammalian TRAPP. Supporting Evidence: PMID:21525244 depletion of C11 (Supplemental Figure 5) resulted in a partial disassembly of the TRAPP complex PMID:21525244 this protein stabilizes the TRAPP complex in mammalian cells |
| GO:0005794 Golgi apparatus | IDA PMID:27862579 Mutations in TRAPPC11 are associated with a congenital disor... | ACCEPT | Summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology. Reason: Accept as a supported cellular location. UniProt maps TRAPPC11 to the Golgi apparatus with PMID:27862579 support, and the CDG abstract reports delayed Golgi vesicular transport caused by TRAPPC11 mutation. Supporting Evidence: file:human/TRAPPC11/TRAPPC11-uniprot.txt Golgi apparatus {ECO:0000269|PubMed:27862579} PMID:27862579 delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex PMID:21525244 RNAi against C8, C11, or C12 resulted in Golgi fragmentation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8877475 | ACCEPT | Summary: Cytosol is consistent with TRAPPC11 as a soluble/peripheral TRAPP trafficking subunit. Reason: Accept as a supported location/context for TRAPPC11-containing TRAPP reactions. The complex is modeled as a cytosolic/peripheral trafficking GEF recruited to early secretory membranes. Supporting Evidence: PMID:21525244 Localization of subunits by fluorescence microscopy has proven difficult due to the large soluble pools of the proteins 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:0097352 autophagosome maturation | IMP PMID:31575891 Characterization of three TRAPPC11 variants suggests a criti... | NEW | Summary: TRAPPC11 supports autophagosome maturation/sealing in a variant-dependent mammalian cell context. Reason: Add as a new direct process annotation. Patient fibroblasts with TRAPPC11 variants show defective starvation-induced autophagic flux, poor LC3/LAMP1 colocalization, and failure to seal isolation membranes into autophagosomes; this is more specific than a generic autophagy row for the accessible evidence. Supporting Evidence: PMID:31575891 displayed an autophagic flux defect PMID:31575891 LC3-II could not be cleared from the cells over the time course of starvation examined PMID:31575891 poor starvation-dependent co-localization PMID:31575891 failed to seal isolation membranes into autophagosomes PMID:31575891 the extreme carboxy-terminus of TRAPPC11, but not residue Gly980, is critical for starvation-induced autophagy file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md defective starvation-induced autophagic flux |
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Download this section (compressed HTML)Q: Should human TRAPPC11 be curated specifically as a TRAPPIII subunit rather than only as a generic TRAPP complex component?
Suggested experts: ComplexPortal curators, Reactome TRAPP curators, GO cellular component editors
Q: Should human TRAPPC11 be curated specifically to autophagosome maturation based on variant-cell autophagosome sealing assays, or should this remain a broader macroautophagy/autophagy annotation in GOA?
Suggested experts: GO autophagy editors, TRAPP/autophagy researchers
Q: Should COPII coat assembly and obsolete tethering annotations on TRAPP subunits be systematically replaced by ER-to-Golgi vesicle-mediated transport when coat assembly or tethering is not directly shown?
Suggested experts: GO transport editors, Reactome TRAPP curators
Experiment: Rescue TRAPPC11-depleted cells with wild-type and disease-associated TRAPPC11 variants, then measure VSV-G ER-to-ERGIC/Golgi transport, Golgi morphology, and TRAPP complex assembly by native fractionation.
Hypothesis: TRAPPC11 supports early secretory transport by stabilizing mammalian TRAPP/TRAPPIII architecture.
Type: secretory cargo rescue and complex stability assay
Experiment: Reconstitute TRAPPC11-containing TRAPPIII and measure RAB1 GDP-to-GTP exchange with and without TRAPPC11 depletion or mutant replacement.
Hypothesis: TRAPPC11 contributes to complex-level TRAPPIII/RAB1 GEF function through assembly or stabilization rather than acting as an independent GEF.
Type: complex reconstitution and RAB1 GEF assay
Experiment: Test TRAPPC11 knockdown/rescue and C-terminal disease variants in starvation-induced LC3-II clearance, LC3/LAMP1 colocalization, and protease protection assays alongside ER-Golgi cargo transport.
Hypothesis: TRAPPC11 C-terminal integrity is required for autophagosome maturation or sealing and can be separated experimentally from some ER-Golgi transport defects.
Type: parallel autophagosome maturation and secretion assay
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