id: Q7Z392 gene_symbol: TRAPPC11 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- 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. alternative_products: - name: '1' id: Q7Z392-1 - name: '2' id: Q7Z392-2 sequence_note: VSP_035095, VSP_035098, VSP_035099 - name: '3' id: Q7Z392-3 sequence_note: VSP_035098, VSP_035099 - name: '4' id: Q7Z392-4 sequence_note: VSP_035096, VSP_035097 existing_annotations: - term: id: GO:0005794 label: Golgi apparatus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology. action: ACCEPT 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. additional_reference_ids: - PMID:27862579 - file:human/TRAPPC11/TRAPPC11-uniprot.txt - PMID:21525244 supported_by: - &id015 reference_id: file:human/TRAPPC11/TRAPPC11-uniprot.txt supporting_text: Golgi apparatus {ECO:0000269|PubMed:27862579} - &id006 reference_id: PMID:27862579 supporting_text: delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex - &id010 reference_id: PMID:21525244 supporting_text: RNAi against C8, C11, or C12 resulted in Golgi fragmentation - 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 soluble/peripheral TRAPP complex biology. action: ACCEPT 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. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-8877475 supported_by: - &id016 reference_id: PMID:21525244 supporting_text: Localization of subunits by fluorescence microscopy has proven difficult due to the large soluble pools of the proteins - &id001 reference_id: PMID:21525244 supporting_text: TRAPP functions either at ER exit sites or at peripheral ERGIC (BFA-resistant) elements - &id017 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: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII. action: ACCEPT 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. additional_reference_ids: - PMID:21525244 - PMID:19942856 - PMID:27066478 - Reactome:R-HSA-8877475 - file:human/TRAPPC11/TRAPPC11-uniprot.txt supported_by: - &id002 reference_id: PMID:21525244 supporting_text: Specifically, we implicate C11 in membrane traffic between the ER and the ERGIC compartment - &id009 reference_id: PMID:21525244 supporting_text: knockdowns of either C11 or C12 arrest a cargo protein in a BFA-resistant compartment - *id001 - &id003 reference_id: PMID:19942856 supporting_text: RNAi of human Gryzun (C4orf41) blocks Golgi exit - &id007 reference_id: file:human/TRAPPC11/TRAPPC11-uniprot.txt supporting_text: Involved in endoplasmic reticulum to Golgi apparatus - &id004 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 TRAPPC11 as a coat-assembly factor. action: MODIFY 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_replacement_terms: - &id005 id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport additional_reference_ids: - PMID:21525244 - PMID:19942856 - Reactome:R-HSA-8877475 supported_by: - *id002 - *id001 - *id003 - *id004 - 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 TRAPPC11/TRAPP process. Mammalian TRAPP tethering remains unresolved and this GO term is obsolete. proposed_replacement_terms: - *id005 additional_reference_ids: - PMID:27066478 - PMID:21525244 - PMID:19942856 supported_by: - reference_id: PMID:27066478 supporting_text: evidence that any TRAPP complex acts as a membrane tether is currently inconclusive - *id002 - *id001 - *id003 - term: id: GO:1990072 label: TRAPPIII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC11 is modeled as a mammalian TRAPPIII-associated subunit. action: ACCEPT 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. additional_reference_ids: - PMID:27066478 - PMID:27862579 - PMID:21525244 - Reactome:R-HSA-8877475 supported_by: - &id018 reference_id: PMID:27066478 supporting_text: TRAPP III, which contains core TRAPP plus TrappC8, 11-13 - reference_id: PMID:27066478 supporting_text: TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13 - *id006 - &id008 reference_id: PMID:21525244 supporting_text: C4orf41 and TTC-15 interact both with each other and with previously characterized TRAPP subunits - 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:0045054 label: constitutive secretory pathway evidence_type: IMP original_reference_id: PMID:19942856 qualifier: involved_in review: summary: TRAPPC11 is directly supported as an early secretory pathway factor. action: ACCEPT 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. additional_reference_ids: - PMID:19942856 - PMID:21525244 - file:human/TRAPPC11/TRAPPC11-uniprot.txt supported_by: - *id003 - *id002 - &id011 reference_id: PMID:21525244 supporting_text: These results imply that the three novel TRAPP-associated proteins function in the early secretory pathway - *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 TRAPPC11 function. action: MARK_AS_OVER_ANNOTATED 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. additional_reference_ids: - PMID:21525244 - PMID:27066478 supported_by: - *id008 - &id012 reference_id: PMID:21525244 supporting_text: These results firmly establish the newly identified proteins as stable TRAPP interactors - &id013 reference_id: PMID:21525244 supporting_text: we report two novel TRAPP proteins, C4orf41/Gryzun (now designated TRAPPC11) and TTC-15 (now designated TRAPPC12) - &id014 reference_id: PMID:27066478 supporting_text: 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 - 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: TRAPPC11 participates in early secretory ER-to-ERGIC/Golgi transport through TRAPP/TRAPPIII. action: ACCEPT 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. additional_reference_ids: - PMID:21525244 - PMID:19942856 - PMID:27066478 - Reactome:R-HSA-8877475 - file:human/TRAPPC11/TRAPPC11-uniprot.txt supported_by: - *id002 - *id009 - *id001 - *id003 - *id007 - *id004 - 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 TRAPPC11-depletion 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 TRAPPC11/TRAPP disruption, while the core process is ER-to-ERGIC/Golgi trafficking and TRAPP complex stability. additional_reference_ids: - PMID:21525244 supported_by: - *id010 - *id011 - term: id: GO:0030008 label: TRAPP complex evidence_type: IMP original_reference_id: PMID:21525244 qualifier: part_of review: summary: TRAPPC11 is a mammalian TRAPP complex component. action: ACCEPT reason: Accept as core cellular-component membership. TAP purification and coimmunoprecipitation identify C4orf41/TRAPPC11 as stably associated with mammalian TRAPP subunits. additional_reference_ids: - PMID:21525244 - PMID:27066478 - file:human/TRAPPC11/TRAPPC11-uniprot.txt supported_by: - *id008 - *id012 - *id013 - *id014 - reference_id: file:human/TRAPPC11/TRAPPC11-uniprot.txt supporting_text: Component of the multisubunit TRAPP (transport protein - term: id: GO:0061635 label: regulation of protein complex stability evidence_type: IMP original_reference_id: PMID:21525244 qualifier: involved_in review: summary: TRAPPC11 supports mammalian TRAPP complex stability. action: ACCEPT 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. additional_reference_ids: - PMID:21525244 supported_by: - &id019 reference_id: PMID:21525244 supporting_text: depletion of C11 (Supplemental Figure 5) resulted in a partial disassembly of the TRAPP complex - &id020 reference_id: PMID:21525244 supporting_text: this protein stabilizes the TRAPP complex in mammalian cells - term: id: GO:0005794 label: Golgi apparatus evidence_type: IDA original_reference_id: PMID:27862579 qualifier: located_in review: summary: Golgi localization is supported for TRAPPC11/TRAPPIII trafficking biology. action: ACCEPT 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. additional_reference_ids: - PMID:27862579 - file:human/TRAPPC11/TRAPPC11-uniprot.txt - PMID:21525244 supported_by: - *id015 - *id006 - *id010 - 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 TRAPPC11 as a soluble/peripheral TRAPP trafficking subunit. action: ACCEPT 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. additional_reference_ids: - PMID:21525244 - Reactome:R-HSA-8877475 supported_by: - *id016 - *id017 - term: id: GO:0097352 label: autophagosome maturation evidence_type: IMP original_reference_id: PMID:31575891 qualifier: involved_in review: summary: TRAPPC11 supports autophagosome maturation/sealing in a variant-dependent mammalian cell context. action: NEW 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. additional_reference_ids: - file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md supported_by: - &id021 reference_id: PMID:31575891 supporting_text: displayed an autophagic flux defect - &id022 reference_id: PMID:31575891 supporting_text: LC3-II could not be cleared from the cells over the time course of starvation examined - &id023 reference_id: PMID:31575891 supporting_text: poor starvation-dependent co-localization - &id024 reference_id: PMID:31575891 supporting_text: failed to seal isolation membranes into autophagosomes - &id025 reference_id: PMID:31575891 supporting_text: the extreme carboxy-terminus of TRAPPC11, but not residue Gly980, is critical for starvation-induced autophagy - reference_id: file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md supporting_text: defective starvation-induced autophagic flux references: - 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: PMID:19942856 title: A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway. 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:27066478 title: TRAPP Complexes in Secretion and Autophagy. findings: [] - id: PMID:27862579 title: Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation. findings: [] - id: PMID:31575891 title: Characterization of three TRAPPC11 variants suggests a critical role for the extreme carboxy terminus of the protein. findings: [] - id: Reactome:R-HSA-8877475 title: TRAPPC complexes exchange GTP for GDP on RAB1 findings: [] - id: file:human/TRAPPC11/TRAPPC11-uniprot.txt title: UniProtKB record for TRAPPC11 findings: [] - id: file:human/TRAPPC11/TRAPPC11-deep-research-falcon.md title: Falcon deep research report for TRAPPC11 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: TRAPPC11 contributes a metazoan TRAPP/TRAPPIII-associated subunit needed for stable TRAPP architecture, early secretory pathway traffic between ER, ERGIC, and Golgi, and autophagosome maturation/sealing in variant-sensitive mammalian cell contexts. It should be modeled as contributing to complex-level TRAPP/RAB1 GEF activity and TRAPP stability rather than independently enabling GEF activity or COPII coat assembly. directly_involved_in: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport - id: GO:0045054 label: constitutive secretory pathway - id: GO:0061635 label: regulation of protein complex stability - id: GO:0097352 label: autophagosome maturation locations: - id: GO:0005829 label: cytosol - id: GO:0005737 label: cytoplasm - id: GO:0005794 label: Golgi apparatus supported_by: - *id017 - *id018 - *id008 - *id012 - *id002 - *id009 - *id001 - *id003 - *id019 - *id020 - *id015 - *id021 - *id022 - *id024 proposed_new_terms: [] suggested_questions: - question: Should human TRAPPC11 be curated specifically as a TRAPPIII subunit rather than only as a generic TRAPP complex component? experts: - ComplexPortal curators - Reactome TRAPP curators - GO cellular component editors - question: 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? experts: - GO autophagy editors - TRAPP/autophagy researchers - question: 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? experts: - GO transport editors - Reactome TRAPP curators suggested_experiments: - description: 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. experiment_type: secretory cargo rescue and complex stability assay hypothesis: TRAPPC11 supports early secretory transport by stabilizing mammalian TRAPP/TRAPPIII architecture. - description: Reconstitute TRAPPC11-containing TRAPPIII and measure RAB1 GDP-to-GTP exchange with and without TRAPPC11 depletion or mutant replacement. experiment_type: complex reconstitution and RAB1 GEF assay hypothesis: TRAPPC11 contributes to complex-level TRAPPIII/RAB1 GEF function through assembly or stabilization rather than acting as an independent GEF. - description: 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. experiment_type: parallel autophagosome maturation and secretion assay hypothesis: TRAPPC11 C-terminal integrity is required for autophagosome maturation or sealing and can be separated experimentally from some ER-Golgi transport defects.