Affinage

TRAPPC5

Trafficking protein particle complex subunit 5 · UniProt Q8IUR0

Round 2 corrected
Length
188 aa
Mass
20.8 kDa
Annotated
2026-04-28
35 papers in source corpus 8 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRAPPC5 is a core subunit of the evolutionarily conserved TRAPP tethering complex that contributes to guanine nucleotide exchange factor (GEF) activity toward Rab1/Ypt1 GTPases and participates in ER-to-Golgi vesicle trafficking (PMID:27066478, PMID:35080977). Binary interaction mapping and large-scale affinity purification–mass spectrometry confirm TRAPPC5 as an integral component of the mammalian TRAPP assembly, where it co-purifies with other core and complex-specific subunits and localizes to the Golgi apparatus (PMID:21525244, PMID:26186194, PMID:35271311). Cryo-EM structures of the yeast TRAPPII complex show that the core module containing the TRAPPC5 ortholog directly contacts the nucleotide-binding domain of the Rab GTPase Ypt32, providing the structural basis for catalytic nucleotide exchange (PMID:35080977). In hepatocellular carcinoma cells, TRAPPC5 is required downstream of MCT4 for cell proliferation, migration, invasion, and epithelial–mesenchymal transition, and its knockdown suppresses xenograft tumor growth (PMID:35425722).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2011 Medium

    Binary interaction mapping established that TRAPPC5 is embedded within the core mammalian TRAPP assembly and that mammalian TRAPP does not recapitulate the yeast TRAPPI sub-complex architecture, redefining the minimal functional unit of mammalian TRAPP.

    Evidence Co-immunoprecipitation and binary interaction mapping of all known mammalian TRAPP subunits

    PMID:21525244

    Open questions at the time
    • No direct structural data on TRAPPC5 contacts within the mammalian TRAPP assembly
    • Single-lab study without independent replication at the time
  2. 2015 Medium

    Large-scale affinity purification–mass spectrometry independently confirmed TRAPPC5 as a component of the endogenous human TRAPP complex, validating earlier binary mapping data with an orthogonal proteomics approach.

    Evidence AP-MS (BioPlex) in HEK293T cells, reproduced across BioPlex 2.0 and 3.0 datasets

    PMID:26186194 PMID:28514442 PMID:33961781

    Open questions at the time
    • Stoichiometry and copy number of TRAPPC5 within the complex not determined
    • No functional readout beyond co-purification
  3. 2016 Medium

    Synthesis of reconstitution, structural, and genetic data across organisms established that the core TRAPP subunits including TRAPPC5 self-assemble into a stable module with GEF activity toward Ypt1/Rab1, placing TRAPPC5 in the ER-to-Golgi trafficking pathway.

    Evidence Review integrating biochemical reconstitution, structural, and genetic epistasis data from multiple groups

    PMID:27066478

    Open questions at the time
    • Direct contribution of TRAPPC5 to GEF catalysis versus structural scaffolding not resolved
    • No mammalian-specific reconstitution of core TRAPP GEF activity with purified TRAPPC5
  4. 2022 High

    Cryo-EM structures of yeast TRAPPII revealed that the core module (containing the TRAPPC5 ortholog) directly contacts the Rab GTPase nucleotide-binding domain, providing the first high-resolution structural basis for TRAPP GEF activity and conformational dynamics upon substrate binding.

    Evidence Cryo-EM structure determination of TRAPPII in apo and Ypt32-bound states with mutagenesis validation

    PMID:35080977

    Open questions at the time
    • Structure is of the yeast ortholog; mammalian TRAPPC5-containing TRAPP structure not yet determined
    • Individual contribution of TRAPPC5 versus neighboring core subunits to substrate contact not dissected by point mutagenesis
  5. 2022 Medium

    Endogenous tagging and live-cell imaging localized TRAPPC5 to the Golgi apparatus in human cells, directly linking its subcellular distribution to its role in Golgi-associated vesicle tethering.

    Evidence CRISPR endogenous fluorescent tagging with confocal live-cell imaging in human cells (OpenCell)

    PMID:35271311

    Open questions at the time
    • Dynamic trafficking of TRAPPC5 between ER-Golgi intermediate compartment and cis-Golgi not resolved
    • Whether TRAPPC5 also localizes to TRAPPIII-specific autophagic membranes not tested
  6. 2022 Medium

    Functional studies in hepatocellular carcinoma demonstrated that TRAPPC5 is required for MCT4-driven cell proliferation, migration, invasion, and EMT, extending TRAPPC5's relevance beyond canonical vesicle trafficking to cancer biology.

    Evidence RNAi knockdown with proliferation, migration, invasion, EMT marker, and xenograft assays in HCC cells

    PMID:35425722

    Open questions at the time
    • Mechanism linking TRAPPC5 vesicle-trafficking function to EMT and proliferation not defined
    • Whether the cancer phenotype depends on intact TRAPP complex activity or a TRAPP-independent role of TRAPPC5 is unknown
    • Single-lab study in one cancer type

Open questions

Synthesis pass · forward-looking unresolved questions
  • The specific catalytic versus scaffolding contribution of TRAPPC5 within the core TRAPP GEF module remains unresolved, and no mammalian high-resolution structure of a TRAPPC5-containing TRAPP complex has been determined.
  • No mammalian cryo-EM or crystal structure of TRAPPC5 in complex
  • No loss-of-function studies distinguishing TRAPPC5's role in TRAPPII versus TRAPPIII
  • No disease-causing mutations in TRAPPC5 reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Localization
GO:0005794 Golgi apparatus 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5
Partners
MCT4TRAPPC1TRAPPC2TRAPPC3TRAPPC4
Complex memberships
TRAPP complex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 TRAPPC5 (along with other core subunits) is a component of the mammalian TRAPP tethering complex. Binary interaction mapping of all known mammalian TRAPP components placed TRAPPC5 within the core TRAPP assembly, and evidence was presented that mammalian TRAPP does not form a TRAPPI-equivalent sub-complex as in yeast, suggesting the fundamental unit of mammalian TRAPP differs from the yeast counterpart. Co-immunoprecipitation, binary interaction mapping, and functional complementation assays across all known mammalian TRAPP subunits Molecular biology of the cell Medium 21525244
2016 TRAPPC5 is identified as a core TRAPP subunit conserved from yeast to humans. Core TRAPP subunits, including the TRAPPC5 homolog, self-assemble into a stable complex with guanine nucleotide exchange factor (GEF) activity toward Ypt1/Rab1, placing TRAPPC5 in the pathway of ER-to-Golgi vesicle tethering and Rab GTPase activation. Review synthesizing biochemical reconstitution, structural, and genetic epistasis data from the TRAPP field Frontiers in cell and developmental biology Medium 27066478
2022 Cryo-EM structures of yeast TRAPPII (which contains the TRAPPC5 ortholog as part of core TRAPP) in apo and Ypt32-bound states reveal a dimeric architecture. The core TRAPP module (including the TRAPPC5 ortholog) directly contacts the nucleotide-binding domain of Ypt32, providing the structural basis for GEF activity, while TRAPPII-specific subunit Trs120 also contacts Ypt32. The monomer transitions between open and closed conformations upon Ypt32 binding. Cryo-EM structure determination combined with functional GEF activity assays and mutagenesis Science advances High 35080977
2022 TRAPPC5 expression is regulated downstream of MCT4 (monocarboxylate transporter 4) in hepatocellular carcinoma cells. Knockdown of TRAPPC5 reduced HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), and suppressed tumor growth in xenograft models, placing TRAPPC5 as a functionally required downstream effector of MCT4-driven HCC progression. RNA interference knockdown of TRAPPC5, CCK-8 proliferation assay, colony formation, transwell/wound-healing migration/invasion assays, western blot for EMT markers, xenograft tumor growth assay Journal of hepatocellular carcinoma Medium 35425722
2015 High-throughput affinity purification-mass spectrometry (BioPlex) identified TRAPPC5 as part of a protein community corresponding to the TRAPP complex in human HEK293T cells, confirming its membership in the endogenous human TRAPP complex and its co-complex associations with other TRAPP subunits. High-throughput affinity purification coupled to mass spectrometry (AP-MS) in HEK293T cells Cell Medium 26186194 28514442 33961781
2022 OpenCell endogenous tagging and live-cell imaging localized TRAPPC5 to the Golgi apparatus in human cells, consistent with its role as a TRAPP complex subunit involved in vesicle tethering at the Golgi. Endogenous CRISPR tagging with fluorescent protein followed by confocal live-cell imaging and AP-MS interaction profiling Science (New York, N.Y.) Medium 35271311

Source papers

Stage 0 corpus · 35 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2014 Proximity biotinylation and affinity purification are complementary approaches for the interactome mapping of chromatin-associated protein complexes. Journal of proteomics 215 25281560
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2011 C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking. Molecular biology of the cell 105 21525244
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2020 Receptor-mediated clustering of FIP200 bypasses the role of LC3 lipidation in autophagy. The EMBO journal 100 33226137
2014 Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress. Molecular & cellular proteomics : MCP 99 24797263
2016 TRAPP Complexes in Secretion and Autophagy. Frontiers in cell and developmental biology 96 27066478
2010 Interactome mapping suggests new mechanistic details underlying Alzheimer's disease. Genome research 96 21163940
2017 Cell cycle-dependent phosphorylation regulates RECQL4 pathway choice and ubiquitination in DNA double-strand break repair. Nature communications 89 29229926
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2019 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. Nature communications 60 31515488
2022 Physical and functional interactome atlas of human receptor tyrosine kinases. EMBO reports 50 35384245
2022 Structural basis for assembly of TRAPPII complex and specific activation of GTPase Ypt31/32. Science advances 18 35080977
2020 Long noncoding RNA and messenger RNA abnormalities in pediatric sepsis: a preliminary study. BMC medical genomics 13 32151258
2022 MCT4 Promotes Hepatocellular Carcinoma Progression by Upregulating TRAPPC5 Gene. Journal of hepatocellular carcinoma 12 35425722
2022 Genetic Parameter Estimation and Whole Sequencing Analysis of the Genetic Architecture of Chicken Keel Bending. Frontiers in genetics 4 35401685
2014 [Differentially expressed genes identified in the main olfactory epithelium of mice with deficiency of adenylate cyclase 3 by using suppression subtractive hybridization approach]. Yi chuan = Hereditas 2 24929516