id: A5PLN9 gene_symbol: TRAPPC13 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- TRAPPC13/C5orf44 is a Trs65-related large TRAPP subunit curated in human TRAPPII and TRAPPIII complex contexts. Its main role is contribution to TRAPP complex RAB1/Rab GEF trafficking and ER-to-Golgi vesicle-mediated transport, rather than independent GEF activity, COPII coat assembly, generic protein binding, or a direct TRAPPC13-specific autophagy function. alternative_products: - name: '1' id: A5PLN9-1 - name: '2' id: A5PLN9-2 sequence_note: VSP_038356 - name: '3' id: A5PLN9-4 sequence_note: VSP_038356, VSP_038359 - name: '4' id: A5PLN9-5 sequence_note: VSP_038359 - name: '5' id: A5PLN9-7 sequence_note: VSP_038356, VSP_038357, VSP_038358 existing_annotations: - term: id: GO:1990072 label: TRAPPIII protein complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: TRAPPC13 is supportable as a mammalian TRAPPIII-associated TRAPP subunit, while its exact TRAPPII/TRAPPIII partition remains source-dependent. Cryo-EM of metazoan TRAPPIII positions TRAPPC13, with TRAPPC12, at the vertex where the TRAPPC8 and TRAPPC11 arms meet, consistent with bona fide TRAPPIII membership. action: ACCEPT reason: Accept as PN-relevant complex membership. GO Central, UniProt, and the TRAPP review place human TRAPPC13 in TRAPP complex context, and the review specifically notes mammalian TRAPP III contains core TRAPP plus TrappC8, 11-13. The falcon deep research summarizes Galindo et al. (2021) cryo-EM placing TRAPPC13 as a metazoan TRAPPIII-specific subunit at the arm vertex, providing structural corroboration of TRAPPIII membership. additional_reference_ids: - PMID:27066478 - file:human/TRAPPC13/TRAPPC13-uniprot.txt - Reactome:R-HSA-8877475 - file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supported_by: - 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 - reference_id: PMID:27066478 supporting_text: The inclusion of TrappC13, the homolog of Trs65, in the mammalian TRAPP III differs from its inclusion in the yeast TRAPP II complex - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: GO; GO:1990072; C:TRAPPIII protein complex; IBA:GO_Central. - 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) - reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supporting_text: High-resolution cryo-EM analysis from Galindo et al. (2021) definitively positioned TRAPPC13, together with TRAPPC12, at the vertex where the TRAPPC8 and TRAPPC11 arms meet - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21453443 qualifier: enables review: summary: Generic protein binding is not informative for TRAPPC13 function. The interactions captured are with other TRAPP subunits, consistent with TRAPPC13's role as a structural/accessory subunit positioned at the vertex of the TRAPPIII arms rather than an independent binding partner. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The PMID:21453443/IntAct evidence reflects interactions with TRAPP components and is better captured as TRAPP complex membership and complex-level trafficking function. The falcon deep research reinforces that TRAPPC13 is best understood as a structural/accessory subunit contributing to complex organization, not via a generic protein-binding function. additional_reference_ids: - PMID:21453443 - file:human/TRAPPC13/TRAPPC13-uniprot.txt - file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supported_by: - reference_id: PMID:21453443 supporting_text: proteins related to Trs85, Trs65 and Tca17 are part of the same TRAPP complex in - reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supporting_text: TRAPPC13 is therefore best understood as a **structural/accessory subunit** rather than the catalytic GEF center. - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: "A5PLN9; Q9UL33: TRAPPC2L; NbExp=3" - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: "A5PLN9; O43617: TRAPPC3; NbExp=2" - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: "A5PLN9; Q9Y2L5: TRAPPC8; NbExp=2" - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Generic protein binding from a proteome-scale AP-MS map is not an informative TRAPPC13 molecular-function annotation. action: MARK_AS_OVER_ANNOTATED reason: Mark as over-annotated. The BioPlex-style interactome evidence can support interaction context, but the more informative representation for TRAPPC13 is TRAPP complex membership and complex-level trafficking. additional_reference_ids: - PMID:33961781 - file:human/TRAPPC13/TRAPPC13-uniprot.txt supported_by: - reference_id: PMID:33961781 supporting_text: These networks model the interactome whose structure encodes protein function, localization, and complex membership - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: "A5PLN9; Q9UL33: TRAPPC2L; NbExp=3" - 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 TRAPPC13-containing TRAPP biology. action: ACCEPT reason: Accept as broad supported cellular location/context. UniProt/ComplexPortal includes the cytoplasm row, and TRAPPC13 participates in cytosolic/peripheral TRAPP trafficking complexes. additional_reference_ids: - file:human/TRAPPC13/TRAPPC13-uniprot.txt - Reactome:R-HSA-8877475 supported_by: - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: GO; GO:0005737; C:cytoplasm; NAS:ComplexPortal. - 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: TRAPPC13-containing TRAPP complex context supports ER-to-Golgi vesicle-mediated transport. action: ACCEPT reason: Accept as the best supported process-level annotation. Reactome models TRAPPC complexes II and III as RAB1 GEFs in COPII-mediated ER-to-ERGIC/Golgi traffic, and UniProt/ComplexPortal carries the ER-to-Golgi transport row. The falcon deep research reinforces that TRAPPC13, via its TRAPPIII context, supports Rab1 activation in ER-to-Golgi vesicular transport (a complex-level role, not a TRAPPC13-autonomous activity). additional_reference_ids: - Reactome:R-HSA-8877475 - PMID:27066478 - file:human/TRAPPC13/TRAPPC13-uniprot.txt - file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supported_by: - reference_id: Reactome:R-HSA-8877475 supporting_text: RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC - 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 - reference_id: PMID:27066478 supporting_text: The mammalian Golgi TRAPP II (see above) was shown to act in vitro as a Rab1, but not Rab11, GEF - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; NAS:ComplexPortal. - reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supporting_text: TRAPPC13, through its role in TRAPPIII, is essential for ER-to-Golgi vesicular transport - term: id: GO:0006901 label: vesicle coat assembly evidence_type: NAS original_reference_id: PMID:27066478 qualifier: involved_in review: summary: The coat-assembly annotation captures COPII-associated transport context but overstates TRAPPC13 as a coat assembly factor. action: MODIFY reason: Modify to ER-to-Golgi vesicle-mediated transport. The accessible evidence supports TRAPP complex recruitment/RAB1 exchange in COPII-associated early secretory traffic, not direct assembly of a vesicle coat by TRAPPC13. proposed_replacement_terms: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport additional_reference_ids: - Reactome:R-HSA-8877475 - PMID:27066478 supported_by: - reference_id: Reactome:R-HSA-8877475 supporting_text: RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC - reference_id: Reactome:R-HSA-8877475 supporting_text: TRAPPCII is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein SEC23 - reference_id: PMID:27066478 supporting_text: These findings provide information of TRAPP interactions with one membrane - 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 TRAPPC13 TRAPP process. The term is obsolete and the review literature cautions that direct TRAPP membrane-tethering evidence remains inconclusive. proposed_replacement_terms: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport additional_reference_ids: - PMID:27066478 - Reactome:R-HSA-8877475 supported_by: - reference_id: PMID:27066478 supporting_text: evidence that any TRAPP complex acts as a membrane tether is currently inconclusive - reference_id: PMID:27066478 supporting_text: evidence for a direct role for TRAPP complexes in membrane tethering is lacking - 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:1990071 label: TRAPPII protein complex evidence_type: NAS original_reference_id: PMID:27066478 qualifier: part_of review: summary: TRAPPC13 is supportable as part of human TRAPPII complex context, especially from UniProt/ComplexPortal and Trs65/TRAPPII literature. action: ACCEPT reason: Accept as supported complex membership/context. UniProt lists TRAPPII ComplexPortal membership for TRAPPC13, and TRAPPC13 is the human Trs65 homolog, a TRAPP II-specific subunit in yeast; mammalian assignments differ between TRAPPII and TRAPPIII sources, so both complex rows should be retained with this caveat. additional_reference_ids: - PMID:21453443 - PMID:27066478 - file:human/TRAPPC13/TRAPPC13-uniprot.txt supported_by: - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: GO; GO:1990071; C:TRAPPII protein complex; NAS:ComplexPortal. - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: ComplexPortal; CPX-4749; TRAPP II complex, TRAPPC2 variant. - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: ComplexPortal; CPX-6902; TRAPP II complex, TRAPPC2B variant. - reference_id: PMID:27066478 supporting_text: Trs65 (560)TrappC13 (C5orf44) (417)Yeast TRAPP II assembly, dimer formation - reference_id: PMID:21453443 supporting_text: Trs65 and Tca17 interact with distinct domains of Trs130 - 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 TRAPPC13-containing TRAPP trafficking reactions. action: ACCEPT reason: Accept as supported location/context for soluble/peripheral TRAPP complex biology. additional_reference_ids: - Reactome:R-HSA-8877475 - file:human/TRAPPC13/TRAPPC13-uniprot.txt supported_by: - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: GO; GO:0005829; C:cytosol; TAS:Reactome. - 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 references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: PMID:21453443 title: Organization and assembly of the TRAPPII complex. findings: [] - id: PMID:27066478 title: TRAPP Complexes in Secretion and Autophagy. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: Reactome:R-HSA-8877475 title: TRAPPC complexes exchange GTP for GDP on RAB1 findings: [] - id: file:human/TRAPPC13/TRAPPC13-uniprot.txt title: UniProtKB record for TRAPPC13 findings: [] - id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md title: Falcon deep research report for TRAPPC13 findings: [] reference_review: relevance: HIGH correctness: UNVERIFIED review_notes: >- LLM-synthesized (Edison/Falcon) literature report. It is internally careful to distinguish TRAPPC13 subunit-specific evidence from holo-complex inference: it correctly states TRAPPC13 does NOT itself catalyze nucleotide exchange and that a recombinant "miniTRAPPIII" lacking TRAPPC12/TRAPPC13 still retains Rab1 GEF activity in vitro (subunit-specific, structural/accessory role at the TRAPPC8/TRAPPC11 arm vertex), while attributing Rab1 GEF activity, ER-to-Golgi transport, Golgi homeostasis, and autophagosome formation to the TRAPPIII complex as a whole. Those complex-level claims should be read as holo-complex inference, not TRAPPC13-specific function. The report frames TRAPPC13 primarily as a TRAPPIII subunit (metazoan TRAPPC8/11/12/13), whereas the existing GOA/ComplexPortal annotations also place it in TRAPPII; this TRAPPII/TRAPPIII partition remains source-dependent and unresolved. Underlying primary sources (Galindo 2021 EMBO J cryo-EM; Galindo & Munro 2023 and Bagde & Fromme 2023 FEBS Lett reviews; Hall 2024 TRAPPopathies; Maeda 2025) are not in the publications/ cache and have not been independently verified here, so correctness is left UNVERIFIED. core_functions: - contributes_to_molecular_function: id: GO:0005085 label: guanyl-nucleotide exchange factor activity in_complex: id: GO:1990071 label: TRAPPII protein complex description: TRAPPC13 contributes to human TRAPPII/TRAPP complex trafficking, where Reactome and review literature model mammalian TRAPP complexes as Rab/RAB1 GEFs in early secretory traffic. This is a complex-level contribution, not independent GEF activity or generic protein binding. directly_involved_in: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport locations: - id: GO:0005829 label: cytosol - id: GO:0005737 label: cytoplasm supported_by: - 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 - reference_id: PMID:27066478 supporting_text: The mammalian Golgi TRAPP II (see above) was shown to act in vitro as a Rab1, but not Rab11, GEF - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: GO; GO:1990071; C:TRAPPII protein complex; NAS:ComplexPortal. - reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt supporting_text: Part of the multisubunit TRAPP (transport protein particle) - contributes_to_molecular_function: id: GO:0005085 label: guanyl-nucleotide exchange factor activity in_complex: id: GO:1990072 label: TRAPPIII protein complex description: TRAPPC13 is also curated in mammalian TRAPPIII context, which explains its PN placement under TRAPP complex components. Cryo-EM places TRAPPC13 (with TRAPPC12) at the vertex joining the TRAPPC8 and TRAPPC11 arms, so it is best understood as a structural/accessory subunit that contributes to TRAPPIII assembly and organization rather than to catalysis, since a recombinant miniTRAPPIII lacking TRAPPC12/TRAPPC13 still retains Rab1 GEF activity in vitro. Current evidence supports TRAPPIII/RAB1 complex context and shared TRAPP trafficking semantics, but not a direct TRAPPC13-specific autophagy process annotation. directly_involved_in: - id: GO:0006888 label: endoplasmic reticulum to Golgi vesicle-mediated transport locations: - id: GO:0005829 label: cytosol - id: GO:0005737 label: cytoplasm supported_by: - 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 - reference_id: PMID:27066478 supporting_text: The inclusion of TrappC13, the homolog of Trs65, in the mammalian TRAPP III differs from its inclusion in the yeast TRAPP II complex - 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) - reference_id: PMID:27066478 supporting_text: the connection of the mammalian TRAPP III complex to autophagy is currently not clear - reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supporting_text: TRAPPC13 does not itself catalyze nucleotide exchange but rather supports the guanine nucleotide exchange factor (GEF) activity of the TRAPPIII complex toward Rab1 GTPase - reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md supporting_text: 'a "miniTRAPPIII" complex lacking TRAPPC12 and TRAPPC13 retains Rab1 GEF activity in vitro, indicating these subunits are dispensable for basal catalytic function' proposed_new_terms: [] suggested_questions: - question: Should human TRAPPC13 be curated as TRAPPII, TRAPPIII, or both, given the difference between yeast Trs65/TRAPPII assignment, mammalian genetic-interaction TRAPPIII models, and ComplexPortal TRAPPII entries? experts: - ComplexPortal curators - Reactome TRAPP curators - GO transport editors - question: Should TRAPPC13 generic protein-binding annotations be replaced by more informative TRAPP complex membership and complex-level Rab/RAB GEF annotations? experts: - GO molecular function editors - IntAct curators - question: Is there direct experimental evidence for a TRAPPC13-specific autophagy or ATG9-trafficking annotation, or should PN autophagy context remain limited to TRAPPIII/TRAPP complex membership? experts: - GO autophagy editors - Reactome TRAPP curators suggested_experiments: - description: Reconstitute human TRAPPC13-containing TRAPPII and TRAPPIII assemblies and measure RAB1 nucleotide exchange with and without TRAPPC13. experiment_type: complex reconstitution and RAB GEF assay hypothesis: TRAPPC13 contributes to complex-level RAB1 GEF activity through TRAPP complex assembly or stability rather than acting as an independent enzyme. - description: Deplete and rescue TRAPPC13 in mammalian cells and compare ER-to-Golgi cargo transport, Golgi morphology, RAB1 activation, and TRAPP subunit integrity. experiment_type: trafficking rescue assay hypothesis: TRAPPC13 supports early secretory trafficking by maintaining functional TRAPP complex architecture. - description: Test TRAPPC13 perturbation in ATG9 cycling, LC3/WIPI2 puncta formation, and starvation-induced autophagy alongside TRAPPC8-positive controls. experiment_type: autophagy trafficking assay hypothesis: If TRAPPC13 has a specific PN autophagy role, it should affect TRAPPIII-dependent ATG9/autophagosome initiation readouts beyond generic secretory pathway disruption.