Affinage

TRAPPC10

Trafficking protein particle complex subunit 10 · UniProt P48553

Length
1259 aa
Mass
142.2 kDa
Annotated
2026-06-10
34 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRAPPC10 (mammalian ortholog of yeast Trs130) is a complex-specific subunit of the multisubunit TRAPPII tethering complex that controls Rab-GTPase activation during Golgi membrane traffic (PMID:17041589, PMID:19656848). Together with TRAPPC9, it converts the guanine-nucleotide exchange (GEF) specificity of TRAPP from Rab1/Ypt1 toward Rab11/Ypt31/32, defining the TRAPPII branch of the pathway (PMID:17041589, PMID:34229011). Cryo-EM of the 22-subunit TRAPPII–Rab11 exchange intermediate shows that the Trs130/TRAPPC10 subunit forms a structural 'leg' that positions the catalytic active site distal to the membrane, providing the steric gating that excludes Rab1 while admitting Rab11 (PMID:35559680). The mammalian complex is enriched on COPI-coated vesicles and buds and binds gamma1COP; loss of TRAPPC10 produces accumulation of vesicles near the Golgi and cargo retention in an early Golgi compartment (PMID:19656848). Beyond classical Golgi secretion, TRAPPII activity supports Rab18-dependent lipid-droplet homeostasis—its loss reduces lipolysis, enlarges lipid droplets, and impairs Rab18 recruitment to droplet surfaces—and is required for autophagy and cytoplasm-to-vacuole targeting acting upstream of Ypt31/32 (PMID:28003315, PMID:23078654). Complex integrity depends on a TRAPPC2L–TRAPPC9–TRAPPC10 interaction module: disease mutations that weaken TRAPPC2L binding disrupt TRAPPII function and elevate active Rab11 (PMID:21858081, PMID:30120216). Biallelic loss-of-function variants in TRAPPC10 abolish the protein, destabilize TRAPPC9, cause membrane-trafficking defects rescued only by wild-type TRAPPC10, and underlie a microcephalic neurodevelopmental disease (PMID:35298461).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 Medium

    Established the genetic position of Trs130 in the ARF–TRAPP axis, placing the Ypt31/32 Rab GTPases downstream of it and linking TRAPPII to Arf1 function.

    Evidence Synthetic-lethal and high-copy suppressor screens with arf1Δ and TRS130 in yeast

    PMID:12210902

    Open questions at the time
    • Genetic-only; does not show direct biochemical GEF activity
    • No mammalian validation at this stage
  2. 2005 High

    Distinguished Trs130's trafficking role from Trs120, showing it is required for general secretion and traffic through or from the Golgi rather than endosome-to-Golgi recycling.

    Evidence Temperature-sensitive mutants, EM of aberrant membranes, Sec7p late-Golgi localization in yeast

    PMID:16314430

    Open questions at the time
    • Did not define the molecular substrate of the trafficking step
    • GEF target unresolved here
  3. 2006 High

    Defined the core mechanistic function: the Trs120–Trs130 subcomplex switches TRAPP GEF specificity from Ypt1 to Ypt31/32, explaining how a single tethering machine serves distinct Golgi stages.

    Evidence trs130ts genetics, GEF specificity assays, GTPase localization in yeast

    PMID:17041589

    Open questions at the time
    • Structural basis of the specificity switch not established
    • Mammalian Rab targets not yet defined
  4. 2007 High

    Localized Trs130 to the trans-Golgi and showed it is essential for TRAPPII GEF activity and stabilizes the partner subunit Trs65, linking subunit identity to complex integrity.

    Evidence Genetic interaction, physical interaction, GEF assays, trans-Golgi colocalization in yeast

    PMID:17475775

    Open questions at the time
    • Mechanism of Trs65 stabilization unresolved
    • No mammalian context
  5. 2007 Low

    Clarified that the human TRAPPC10 (TMEM1) protein, despite predicted transmembrane domains, does not function as a transmembrane protein, refining its molecular nature as a soluble subunit.

    Evidence Phylogenetic and secondary-structure analysis with experimental test in yeast

    PMID:17274825

    Open questions at the time
    • Primarily computational with limited experimental validation
    • Membrane-association mode not directly characterized
  6. 2009 High

    Translated the function to mammals, identifying mTRAPPC10 as a COPI-vesicle-enriched TRAPPII component that binds gamma1COP and acts as a GEF, with depletion causing early-Golgi cargo accumulation.

    Evidence shRNA depletion, Co-IP, immuno-EM, GEF assays, cargo trafficking in mammalian cells

    PMID:19656848

    Open questions at the time
    • Rab specificity reported as Rab1 here, later expanded
    • Single lab
  7. 2011 Medium

    Defined the assembly logic in mammalian cells: TRAPPC2 acts as an adaptor through TRAPPC9 to TRAPPC10, and the TRAPPC2L–TRAPPC10 interaction is required for TRAPPII integrity.

    Evidence Reciprocal Co-IP and disease-mutant analysis in mammalian cells

    PMID:21858081

    Open questions at the time
    • Single lab
    • Stoichiometry and architecture not resolved structurally
  8. 2012 High

    Extended TRAPPII function beyond secretion to autophagy and the Cvt pathway, placing Trs130 upstream of Atg1/Atg13/Atg9/Atg14 with Ypt31/32 as the relevant downstream Rabs.

    Evidence trs130ts mutants, Atg8/Atg9 localization, genetic epistasis and Ypt31/32 suppression in yeast

    PMID:23078654

    Open questions at the time
    • Direct biochemical coupling to autophagy machinery not shown
    • Mammalian autophagy role not demonstrated
  9. 2012 High

    Pinned the Rab specificity genetically, showing Ypt31/32 but not Ypt1 overexpression rescues trs130ts phenotypes in Golgi-exit cargo transport.

    Evidence GFP-Snc1 transport assays and Ypt overexpression suppression in yeast

    PMID:22426882

    Open questions at the time
    • Genetic suppression does not prove direct GEF action on each Rab
    • Membrane context not addressed
  10. 2016 High

    Revealed a non-Golgi role, establishing mammalian TRAPPII as a Rab18 (and Rab1) GEF required for Rab18 recruitment to lipid droplets and normal lipolysis, mechanistically linked to the COPI–TRAPPII interaction.

    Evidence siRNA, CRISPR-Cas9 deletion, GEF assays, lipid-droplet imaging, Rab18 localization, rescue in mammalian cells

    PMID:28003315

    Open questions at the time
    • Whether TRAPPC10 acts directly or via complex on Rab18 at droplets not separated
    • Connection between Golgi and droplet pools unclear
  11. 2018 Medium

    Linked the TRAPPC2L–TRAPPC10 interaction directly to human disease, showing a TRAPPC2L p.Asp37Tyr mutation ablates the interaction, delays trafficking, and elevates active RAB11.

    Evidence Yeast two-hybrid, patient fibroblasts, trafficking assays, RAB11 activation measurement

    PMID:30120216

    Open questions at the time
    • Single lab
    • Mechanism linking RAB11 hyperactivation to phenotype not established
  12. 2021 High

    Defined the in vitro Rab repertoire, showing TRAPPII specifically activates Rab1 and Rab11 and that TRAPPC9/TRAPPC10 alter Rab-site dynamics, with membrane association enhancing GEF activity.

    Evidence GEF assays against 20-Rab panel, HDX-MS, EM

    PMID:34229011

    Open questions at the time
    • Single lab
    • Conformational changes mapped but causal residues not fully validated
  13. 2022 High

    Provided the structural mechanism: cryo-EM of a TRAPPII–Rab11 intermediate shows TRAPPC10/Trs130 forms a 'leg' positioning the active site away from the membrane, enabling steric gating against Rab1 while Trs120 acts as a lid for Rab11 access.

    Evidence Cryo-EM structure of 22-subunit TRAPPII exchange intermediate with structural mutagenesis

    PMID:35559680

    Open questions at the time
    • Dynamics of gating in a membrane bilayer not directly visualized
    • How the same architecture handles Rab18 not addressed
  14. 2022 High

    Established TRAPPC10 as a human disease gene, showing biallelic loss-of-function abolishes TRAPPC10 and destabilizes TRAPPC9, causes a trafficking defect rescued only by wild-type protein, and produces neuroanatomical defects in mice.

    Evidence Patient lymphoblastoid cells, TRAPPC10 KO lines, rescue experiments, Trappc10-/- mouse neuroanatomy

    PMID:35298461

    Open questions at the time
    • Cell-type basis of neurodevelopmental phenotype not defined
    • Link from trafficking defect to brain phenotype mechanistically incomplete
  15. 2024 Medium

    Reinforced TRAPPC10 as a TRAPPII-preferential subunit, showing TRAPPC6B variants reduce TRAPPC9/TRAPPC10 levels and impair Golgi trafficking, with TRAPPC6B associating more with TRAPPII.

    Evidence Patient fibroblast protein-level analysis, Co-IP, trafficking assays, rescue in mammalian cells

    PMID:37713627

    Open questions at the time
    • Indirect finding via TRAPPC6B
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRAPPC10 mechanistically couples its membrane-distal GEF architecture to the distinct downstream consequences (Golgi secretion vs lipid-droplet Rab18 activation vs autophagy) and how its loss produces the specific microcephalic neurodevelopmental phenotype remain unresolved.
  • No structural model of TRAPPII engaging Rab18 at lipid droplets
  • Cell-type-specific requirement in brain not defined
  • Direct vs complex-mediated contribution of TRAPPC10 to each Rab not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005794 Golgi apparatus 3 GO:0005811 lipid droplet 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-1430728 Metabolism 1 R-HSA-9612973 Autophagy 1
Partners
GAMMA1COPRAB1RAB11RAB18TRAPPC2TRAPPC2LTRAPPC6BTRAPPC9
Complex memberships
TRAPPII

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 The TRAPPII-specific subunits Trs120 and Trs130 (yeast ortholog of TRAPPC10) are required for switching the GEF specificity of TRAPP from Ypt1 to Ypt31/32. A trs130ts mutation confers opposite effects on the intracellular localization of these GTPases, suggesting the Trs120-Trs130 subcomplex joins TRAPP at the late Golgi to switch GEF activity. Genetic analysis (trs130 temperature-sensitive mutants), GEF specificity assays, intracellular localization studies in yeast Nature cell biology High 17041589
2005 Trs130p (yeast ortholog of TRAPPC10), unlike Trs120p, is required for general secretion and traffic through or from the Golgi; trs130 mutations block vesicular transport at the Golgi, distinct from the early endosome-to-late Golgi recycling defect seen in trs120 mutants. Temperature-sensitive mutant analysis, electron microscopy of aberrant membrane structures, fluorescence localization with late Golgi marker Sec7p The Journal of cell biology High 16314430
2009 Mammalian Trs130 (mTrs130/TRAPPC10) is a component of a mammalian TRAPPII complex that is enriched on COPI-coated vesicles and buds, acts as a GEF specifically activating Rab1, and binds to gamma1COP. Depletion of mTrs130 by shRNA leads to increased vesicles near the Golgi and cargo accumulation in an early Golgi compartment. shRNA depletion, co-immunoprecipitation (binding to gamma1COP), immunoelectron microscopy localization on COPI vesicles, GEF activity assays, cargo trafficking assays Molecular biology of the cell High 19656848
2011 TRAPPC2 binds to TRAPPII-specific subunit TRAPPC9, which in turn binds to TRAPPC10, establishing TRAPPC2 as an adaptor for TRAPPII complex formation in mammalian cells. The interaction between TRAPPC2L and TRAPPC10/Trs130 is required for TRAPPII integrity. Co-immunoprecipitation in mammalian cells, disease-causing mutant analysis (D47Y TRAPPC2, deletional TRAPPC9 mutants) PloS one Medium 21858081
2016 Mammalian TRAPPII (containing TRAPPC10) acts as a GEF for both Rab18 and Rab1. Inactivation of TRAPPII-specific subunits (including via CRISPR-Cas9 deletion) reduces lipolysis, causes aberrantly large lipid droplets, and impairs Rab18 recruitment to lipid droplet surfaces. The previously documented COPI-TRAPPII interaction is required for Rab18 recruitment to lipid droplets. siRNA depletion, CRISPR-Cas9 deletion, GEF activity assays, lipid droplet imaging, Rab18 localization assays The EMBO journal High 28003315
2007 Trs130 (yeast ortholog of TRAPPC10) localizes to the trans-Golgi and is essential for TRAPPII GEF activity toward Ypt31/32. trs130 mutant cells have low levels of Trs65 protein and are defective in GEF activity of TRAPPII and in intracellular distribution of Ypt1 and Ypt31/32. Genetic interaction analysis, physical interaction assays, GEF activity assays, fluorescence localization (trans-Golgi marker co-localization) Molecular biology of the cell High 17475775
2007 Trs130 (TRAPPC10 ortholog) and Trs120 are conserved essential TRAPPII-specific subunits present in almost every fully sequenced eukaryotic genome. Computational analysis and experimental validation showed yeast Trs130 does not function as a transmembrane protein despite the human TMEM1 (TRAPPC10) being initially predicted to have transmembrane domains. Phylogenetic analysis, predicted secondary structure analysis, experimental demonstration that yeast Trs130 lacks transmembrane function BMC evolutionary biology Low 17274825
2012 Trs130 (TRAPPC10 ortholog) is required for both cytoplasm-to-vacuole targeting (Cvt) pathway and starvation-induced autophagy. trs130ts mutants fail to properly transport Atg8 and Atg9 to the pre-autophagosomal structure; genetic analysis placed Trs130 downstream of Atg5 and upstream of Atg1, Atg13, Atg9 and Atg14. Overexpression of Ypt31 or Ypt32, but not Ypt1, rescued autophagy defects in trs130ts mutants. Temperature-sensitive mutant analysis, GFP-Atg8 and Atg9 localization, genetic epistasis analysis, genetic suppression by Ypt31/32 overexpression Traffic (Copenhagen, Denmark) High 23078654
2012 Genetic epistasis in yeast shows that Ypt31/32, but not Ypt1, overexpression suppresses growth and GFP-Snc1 transport phenotypes of trs130ts mutant cells, placing TRAPPII (containing Trs130/TRAPPC10 ortholog) specifically upstream of Ypt31/32 but not Ypt1 in Golgi exit trafficking. Temperature-sensitive mutant analysis, GFP-Snc1 transport assay, genetic suppression by Ypt overexpression Genetics High 22426882
2018 The interaction between TRAPPC2L and TRAPPC10/Trs130 (TRAPPII component) is ablated by a human disease-causing missense mutation in TRAPPC2L (p.Asp37Tyr). This interaction is required for proper TRAPP II complex function; loss of TRAPPC2L-TRAPPC10 interaction results in specific membrane trafficking delays and increased levels of active RAB11. Yeast two-hybrid analysis, patient fibroblast studies, membrane trafficking assays, RAB11 activation state measurements Journal of medical genetics Medium 30120216
2022 Biallelic loss-of-function variants in TRAPPC10 cause absence of TRAPPC10 protein alongside concomitant absence of TRAPPC9, another TRAPP II component. TRAPPC10 knockout cells display a membrane trafficking defect; both TRAPPC9 reduction and the trafficking defect are rescued by wild-type but not mutant TRAPPC10 constructs. Mutant TRAPPC10 shows weakened interaction with TRAPPC2L. Patient lymphoblastoid cell studies, TRAPPC10 knockout cell lines, membrane trafficking assays, protein interaction assays, rescue experiments with wild-type vs. mutant constructs, Trappc10-/- mouse neuroanatomical analysis PLoS genetics High 35298461
2022 Cryo-EM structures of TRAPPII (containing Trs130/TRAPPC10 ortholog) at 22-subunit resolution including a TRAPPII-Rab11 nucleotide exchange intermediate reveal that the Trs130 subunit provides a 'leg' that positions the active site distal to the membrane surface, required for steric gating against Rab1. The Trs120 subunit acts as a 'lid' to enclose the active site, enabling Rab11 to access the active site chamber. Cryo-electron microscopy structure determination, nucleotide exchange intermediate capture, structural mutagenesis analysis Science advances High 35559680
2021 TRAPPII complex (containing TRAPPC10) specifically activates Rab1 and Rab11 as a GEF; the complex-specific subunits TRAPPC9 and TRAPPC10 alter protein dynamics at the Rab binding site compared to TRAPPIII. Both TRAPPII and TRAPPIII have enhanced GEF activity on lipid membranes, with conformational changes accompanying membrane association identified by HDX-MS. GEF activity biochemical assays against panel of 20 Rabs, hydrogen-deuterium exchange mass spectrometry (HDX-MS), electron microscopy Journal of molecular biology High 34229011
2024 Patient-derived fibroblasts with TRAPPC6B variants show reduced levels of TRAPPC9 and TRAPPC10 alongside reduced trafficking into the Golgi apparatus and Golgi fragmentation. TRAPPC6B co-precipitates significantly more with TRAPP II than TRAPP III, suggesting TRAPPC10 levels are preferentially affected by TRAPP II disruption. Patient fibroblast protein level analysis, co-immunoprecipitation, trafficking assays, rescue with wild-type TRAPPC6B Brain : a journal of neurology Medium 37713627
2002 Genetic screen in yeast identified TRS130 (TRAPPC10 ortholog) as a synthetic lethal interactor with arf1Δ. YPT31 and YPT32 were identified as high-copy suppressors of arf1Δ trs130-101, and overexpression of YPT31/32 also suppressed lethality from deletion of TRS130, placing Ypt31/32 downstream of Trs130 in the ARF-TRAPP signaling pathway. Synthetic lethal screen, high-copy suppressor screen, genetic epistasis analysis Yeast (Chichester, England) Medium 12210902
2019 In Aspergillus nidulans, a stable Trs120/Trs130/Trs65/Tca17 TRAPPII-specific subcomplex was discovered, whose assembly onto core TRAPP generates TRAPPII through Trs20- and Trs33-dependent interactions. This modular assembly mechanism was established by exploiting constitutively active RAB mutants to rescue viability of null mutants lacking essential TRAPP subunits. Size-fractionation chromatography, single-step purification coupled to mass spectrometry, negative-stain electron microscopy, constitutively-active RAB mutant genetic rescue PLoS genetics High 31869332

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 TRAPPII subunits are required for the specificity switch of a Ypt-Rab GEF. Nature cell biology 132 17041589
2009 mTrs130 is a component of a mammalian TRAPPII complex, a Rab1 GEF that binds to COPI-coated vesicles. Molecular biology of the cell 106 19656848
2005 Mutants in trs120 disrupt traffic from the early endosome to the late Golgi. The Journal of cell biology 106 16314430
2009 A genome-wide RNA interference screen identifies two novel components of the metazoan secretory pathway. The EMBO journal 90 19942856
2016 COPI-TRAPPII activates Rab18 and regulates its lipid droplet association. The EMBO journal 81 28003315
2015 A genome-wide approach to link genotype to clinical outcome by utilizing next generation sequencing and gene chip data of 6,697 breast cancer patients. Genome medicine 70 26474971
2015 TRAPPII regulates exocytic Golgi exit by mediating nucleotide exchange on the Ypt31 ortholog RabERAB11. Proceedings of the National Academy of Sciences of the United States of America 56 25831508
2011 The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated SEDT and TRAPPC9-associated congenital intellectual disability. PloS one 54 21858081
1995 Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3. Human molecular genetics 53 7633421
2018 Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability. Human genetics 50 30167849
2020 Multi-omics approaches identify SF3B3 and SIRT3 as candidate autophagic regulators and druggable targets in invasive breast carcinoma. Acta pharmaceutica Sinica. B 45 34094830
2007 The role of Trs65 in the Ypt/Rab guanine nucleotide exchange factor function of the TRAPP II complex. Molecular biology of the cell 41 17475775
2007 Conservation of the TRAPPII-specific subunits of a Ypt/Rab exchanger complex. BMC evolutionary biology 37 17274825
2018 Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts. Journal of medical genetics 36 30120216
2012 Modular TRAPP complexes regulate intracellular protein trafficking through multiple Ypt/Rab GTPases in Saccharomyces cerevisiae. Genetics 32 22426882
2016 Cell cycle-regulated PLEIADE/AtMAP65-3 links membrane and microtubule dynamics during plant cytokinesis. The Plant journal : for cell and molecular biology 30 27420177
2012 Trs130 participates in autophagy through GTPases Ypt31/32 in Saccharomyces cerevisiae. Traffic (Copenhagen, Denmark) 29 23078654
2002 Genetic interactions link ARF1, YPT31/32 and TRS130. Yeast (Chichester, England) 27 12210902
2019 Characterization of Aspergillus nidulans TRAPPs uncovers unprecedented similarities between fungi and metazoans and reveals the modular assembly of TRAPPII. PLoS genetics 23 31869332
2002 Mutation of TRS130, which encodes a component of the TRAPP II complex, activates transcription of OCH1 in Saccharomyces cerevisiae. Current genetics 21 12478387
2022 Structure of a TRAPPII-Rab11 activation intermediate reveals GTPase substrate selection mechanisms. Science advances 19 35559680
2022 Biallelic variants in TRAPPC10 cause a microcephalic TRAPPopathy disorder in humans and mice. PLoS genetics 17 35298461
2021 Biochemical Insight into Novel Rab-GEF Activity of the Mammalian TRAPPIII Complex. Journal of molecular biology 15 34229011
2009 Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal. BMC genomics 13 19505301
1997 Localization of 16 exons to a 450-kb region involved in the autoimmune polyglandular disease type I (APECED) on human chromosome 21q22.3. DNA research : an international journal for rapid publication of reports on genes and genomes 13 9179495
1996 Cloning the cDNA of human PWP2, which encodes a protein with WD repeats and maps to 21q22.3. Genomics 11 8661145
1996 A periodic tryptophan protein 2 gene homologue (PWP2H) in the candidate region of progressive myoclonus epilepsy on 21q22.3. Cytogenetics and cell genetics 8 8893822
1997 Genomic organization and complete nucleotide sequence of the TMEM1 gene on human chromosome 21q22.3. Biochemical and biophysical research communications 6 9196060
2024 TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions. Brain : a journal of neurology 5 37713627
2015 Bet3 participates in autophagy through GTPase Ypt1 in Saccharomyces cerevisiae. Cell biology international 5 25581738
1997 Genomic structure of the human GT334 (EHOC-1) gene mapping to 21q22.3. Gene 5 9370297
2015 Ypt1 and TRAPP interactions: optimization of multicolor bimolecular fluorescence complementation in yeast. Methods in molecular biology (Clifton, N.J.) 4 25800836
1997 Genomic organization and complete nucleotide sequence of the human PWP2 gene on chromosome 21. Genomics 4 9205129
2024 Introducing a novel TRAPPC10 gene variant as a potential cause of developmental delay and intellectual disability in an Iranian family. Neurogenetics 1 39560797

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