Affinage

TRAPPC8

Trafficking protein particle complex subunit 8 · UniProt Q9Y2L5

Round 2 corrected
Length
1435 aa
Mass
161.0 kDa
Annotated
2026-04-28
42 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRAPPC8 is the defining subunit of the mammalian TRAPPIII tethering complex, linking vesicle trafficking to autophagosome biogenesis and ciliogenesis. TRAPPC8 is recruited to the TRAPP core via TRAPPC2 in a mutually exclusive manner with TRAPPC9/TRAPPII, and the resulting TRAPPIII complex functions as a GEF for RAB1, regulating ATG9 trafficking from peripheral recycling endosomes to the early Golgi to support autophagosome initiation independently of ULK1 (PMID:26711178, PMID:23129774). At the centrosome/basal body, TRAPPC8 promotes ciliogenesis by facilitating Rabin8 centrosome targeting and the association of OFD1 with PCM1 (PMID:25018876, PMID:32258032). TRAPPC8 also maintains Golgi stack integrity, a function exploited by HPV L2 capsid protein binding to TRAPPC8 to disrupt Golgi organization during viral infection (PMID:24244674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2000 Medium

    Identification of Trs85p as a TRAPP complex subunit established that the complex has additional components beyond the minimal core and is anchored to Golgi membranes for ER-to-Golgi tethering.

    Evidence Biochemical purification, mass spectrometry, and subcellular fractionation in yeast

    PMID:10727015

    Open questions at the time
    • Specific function of Trs85 within TRAPP was not resolved
    • No mammalian homologue identified at this stage
  2. 2005 High

    Demonstrating that Trs85 is required for the Cvt pathway, pexophagy, and macroautophagy in two yeast species established a conserved, specific role for this TRAPP subunit in autophagy-related membrane trafficking.

    Evidence Genetic deletion, GFP-Atg8 fluorescence microscopy, electron microscopy, and selective autophagy assays in S. cerevisiae and Y. lipolytica

    PMID:16079147 PMID:16874038

    Open questions at the time
    • Mechanism by which Trs85 promotes PAS organization was unknown
    • Whether this autophagy role is conserved in mammals was untested
  3. 2011 High

    Identification of TRAPPC8 as the mammalian Trs85 orthologue and demonstration that TRAPPC2 bridges TRAPPC8 into a TRAPPIII complex mutually exclusive with TRAPPC9-containing TRAPPII resolved the architecture of mammalian TRAPP complexes.

    Evidence Binary interaction mapping, co-immunoprecipitation, mass spectrometry, and disease mutant analysis (TRAPPC2-D47Y) in mammalian cells

    PMID:21453443 PMID:21525244 PMID:21858081

    Open questions at the time
    • Whether mammalian TRAPPIII retains GEF activity for Rab1/Ypt1 was not yet shown
    • Structural basis for mutual exclusivity of TRAPPC8 and TRAPPC9 binding to TRAPPC2 was unresolved
  4. 2012 High

    Showing that Trs85 directly interacts with Atg9 and loads Ypt1 onto Atg9 vesicles placed TRAPPIII as a Rab-GEF acting downstream of Atg9 in autophagosome nucleation.

    Evidence Atg9 vesicle purification, direct interaction assay, mass spectrometry, and fluorescence microscopy in yeast

    PMID:23129774

    Open questions at the time
    • Whether mammalian TRAPPC8 similarly interacts with ATG9 was not tested
    • Mechanism by which TRAPPIII recognizes Atg9 vesicles versus other membrane carriers was unclear
  5. 2013 Medium

    Discovery that TRAPPC8 is required for Golgi integrity and is exploited by HPV L2 during infection revealed an unexpected role in maintaining Golgi structure and a viral subversion mechanism.

    Evidence Co-immunoprecipitation, siRNA knockdown, immunofluorescence, and infection assays with authentic HPV virions in HeLa/HaCaT cells

    PMID:24244674

    Open questions at the time
    • Cell-surface exposure of TRAPPC8 was unexpected and awaits independent confirmation
    • Whether Golgi dispersal is a direct consequence of TRAPPC8 loss or secondary to trafficking defects was not distinguished
  6. 2014 Medium

    Localization of endogenous TRAPPC8 to the centrosome/basal body and demonstration that its depletion blocks Rabin8 targeting and ciliogenesis extended TRAPPIII function beyond Golgi trafficking to the primary cilium.

    Evidence Immunofluorescence of endogenous protein, siRNA knockdown with ciliogenesis and Rabin8 centrosome-targeting readouts in mammalian cells

    PMID:25018876

    Open questions at the time
    • Which TRAPPC8 domain mediates centrosome localization was not mapped
    • Whether TRAPPC8's ciliogenesis role requires its GEF-associated activity was untested
  7. 2015 High

    Establishing that TRAPPC8-containing TRAPPIII acts as a RAB1 GEF regulating ATG9 trafficking from recycling endosomes to the early Golgi, independently of ULK1, unified the yeast autophagy findings with mammalian membrane trafficking and autophagy pathways.

    Evidence RAB1 activation assays, ATG9 trafficking assays, autophagy flux measurements, co-immunoprecipitation, and epistasis experiments with ULK1 and TBC1D14

    PMID:26711178

    Open questions at the time
    • Whether TRAPPIII's constitutive secretory role is separable from its autophagy-specific role at the molecular level was not resolved
    • Structural basis for TBC1D14–TRAPPIII interaction was not determined
  8. 2020 Medium

    Showing that TRAPPC8 bridges OFD1 to PCM1 and competes with TRAPPC12 for OFD1 binding provided a molecular mechanism for how TRAPPIII promotes cilium assembly while TRAPPC12 opposes cilium disassembly.

    Evidence Reciprocal co-immunoprecipitation, siRNA knockdown, immunofluorescence, and cilia length measurements in hTERT-RPE1 cells

    PMID:32258032

    Open questions at the time
    • Whether TRAPPC8–OFD1 interaction is direct or requires other centriolar satellite components was not established
    • In vivo consequences of TRAPPC8 loss for cilium-related signaling pathways (e.g., Hedgehog) were not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how TRAPPC8's dual functions at the Golgi/recycling endosome (autophagy, secretion) and the centrosome (ciliogenesis) are spatiotemporally coordinated, and no high-resolution structure of mammalian TRAPPIII incorporating TRAPPC8 has been reported.
  • No structural model of full-length mammalian TRAPPIII
  • Mechanism coordinating TRAPPC8's roles in autophagy versus ciliogenesis is unknown
  • Whether TRAPPC8 mutations cause a human Mendelian disease has not been established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005794 Golgi apparatus 2 GO:0005815 microtubule organizing center 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-9612973 Autophagy 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
ATG9OFD1PCM1TBC1D14TRAPPC2TRAPPC9
Complex memberships
TRAPPIII

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Trs85p was identified as one of five novel subunits of the yeast TRAPP complex, and biochemical characterization showed the complex (including its human homologue) is anchored to a Triton X-100-resistant fraction of the Golgi, implicating TRAPP in ER-to-Golgi vesicle tethering. Biochemical purification, mass spectrometry, subcellular fractionation European journal of cell biology Medium 10727015
2005 Trs85 (Gsg1) is required for the biogenesis of Cvt vesicles and for selective autophagy via the Cvt pathway in S. cerevisiae; trs85Δ cells show defective organization of the preautophagosomal structure and impaired recruitment of GFP-Atg8 to the PAS, while general autophagy proceeds at a reduced rate, indicating a specific role in pre-autophagosomal structure organization. Genetic deletion, fluorescence microscopy (GFP-Atg8 localization), electron microscopy, biochemical assays The Journal of biological chemistry High 16079147
2005 Trs85 is required for macroautophagy, pexophagy, and the cytoplasm-to-vacuole targeting (Cvt) pathway in both Yarrowia lipolytica and Saccharomyces cerevisiae, establishing its conserved role in multiple selective and non-selective autophagy routes. Genetic screen, deletion mutant analysis, selective autophagy assays in two yeast species Autophagy High 16874038
2011 TRAPPC8 (KIAA1012) was identified as the mammalian homologue of yeast Trs85p and confirmed as a bona fide component of human TRAPP; binary interaction mapping showed TRAPPC8 is part of the mammalian TRAPPIII-equivalent complex, and the study established that mammalian TRAPP lacks a TRAPPI-equivalent, with TRAPPC8 and TRAPPC11 being novel components. Co-immunoprecipitation, binary interaction mapping, mass spectrometry, fluorescence microscopy Molecular biology of the cell High 21525244
2011 TRAPPC2 serves as an adaptor for the formation of mammalian TRAPPIII by directly binding TRAPPC8; endogenous TRAPPC9-positive TRAPPII complex does not contain TRAPPC8, establishing that TRAPPC2 binds either TRAPPC9 (for TRAPPII) or TRAPPC8 (for TRAPPIII) in a mutually exclusive manner. A disease-causing mutation D47Y in TRAPPC2 abrogated interaction with TRAPPC8. Co-immunoprecipitation in mammalian cells, disease mutant analysis PloS one Medium 21858081
2011 Trs85 is not associated with the yeast TRAPPII complex but proteins related to Trs85 (TRAPPC8) are part of the same TRAPP complex as Trs65 and Tca17 homologues in mammalian cells, indicating a reorganization of TRAPP complex architecture between yeast and mammals. Affinity purification, mass spectrometry, co-immunoprecipitation in yeast and mammalian cells Traffic (Copenhagen, Denmark) Medium 21453443
2012 Trs85 directly interacts with Atg9 and the Trs85-containing TRAPPIII complex facilitates the association of the Rab GTPase Ypt1 onto Atg9 vesicles; Trs85 and Ypt1 localize to the preautophagosomal structure in an Atg9-dependent manner, placing TRAPPIII downstream of Atg9 in autophagosome formation. Atg9 vesicle purification, mass spectrometry, direct interaction assay, fluorescence microscopy The Journal of biological chemistry High 23129774
2013 TRAPPC8 specifically interacts with HPV L2 capsid protein (MaL2) and is exposed on the cell surface where it colocalizes with inoculated HPV pseudovirions; TRAPPC8 knockdown in HeLa and HaCaT cells reduced susceptibility to HPV51, HPV16, and HPV31 infection independently of L2 interaction, and TRAPPC8 depletion caused dispersal of Golgi stack structure—a phenotype also induced by GFP-L2 overexpression—suggesting that L2 binding to TRAPPC8 inhibits its Golgi maintenance function to facilitate viral escape from the trans-Golgi network. Co-immunoprecipitation, siRNA knockdown, immunofluorescence microscopy, infection assays with authentic virions and pseudovirions PloS one Medium 24244674
2014 TRAPPC8 was identified as containing conserved C-terminal ASH (ASPM, SPD-2, Hydin) domains and N-terminal α-solenoid/TPR repeats by computational analysis; endogenous TRAPPC8 localizes to the centrosome/basal body by immunofluorescence microscopy, and depletion of TRAPPC8 impairs ciliogenesis and prevents GFP-Rabin8 targeting to the centrosome, establishing TRAPPC8 as a ciliogenesis factor acting at the centrosome. Computational domain prediction, immunofluorescence microscopy of endogenous protein, siRNA knockdown with ciliogenesis and centrosome-targeting readouts Cilia Medium 25018876
2015 TRAPPC8 is the mammalian orthologue of the yeast autophagy-specific TRAPP subunit Trs85 and forms part of a mammalian TRAPPIII-like complex; TRAPPC8 and TBC1D14 both regulate ATG9 trafficking and RAB1 activation independently of ULK1, and TRAPPC8 is required for TBC1D14 to bind TRAPPIII. Overexpression of TBC1D14's TRAPP-binding domain inhibits both autophagy and secretory traffic, placing TRAPPIII (containing TRAPPC8) at a constitutive trafficking step from peripheral recycling endosomes to the early Golgi. Co-immunoprecipitation, siRNA knockdown, ATG9 trafficking assays, RAB1 activation assays, autophagy flux assays The EMBO journal High 26711178
2020 TRAPPC8 interacts with the ciliopathy protein OFD1 and is necessary for the association of OFD1 with pericentriolar material 1 (PCM1); TRAPPC8 depletion reduces colocalization of OFD1 and PCM1 without compromising centriolar satellite structural integrity. The interaction between TRAPPC8 and OFD1 is mutually inhibitory with that between OFD1 and TRAPPC12, explaining differential cilium length phenotypes: TRAPPC8 depletion reduces cilium assembly while TRAPPC12 depletion (which blocks cilia disassembly) increases cilium length. Co-immunoprecipitation, siRNA knockdown, immunofluorescence microscopy, cilia length measurements in hTERT-RPE1 cells Frontiers in cell and developmental biology Medium 32258032

Source papers

Stage 0 corpus · 42 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 3439 11805826
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
2010 Network organization of the human autophagy system. Nature 1286 20562859
2008 Identification of host proteins required for HIV infection through a functional genomic screen. Science (New York, N.Y.) 1165 18187620
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
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2004 Phosphoproteomic analysis of the developing mouse brain. Molecular & cellular proteomics : MCP 291 15345747
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome research 151 11230166
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
2015 TBC1D14 regulates autophagy via the TRAPP complex and ATG9 traffic. The EMBO journal 146 26711178
1999 Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA research : an international journal for rapid publication of reports on genes and genomes 112 10231032
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
2000 Identification and characterization of five new subunits of TRAPP. European journal of cell biology 105 10727015
2016 TRAPP Complexes in Secretion and Autophagy. Frontiers in cell and developmental biology 96 27066478
2012 Atg9 vesicles recruit vesicle-tethering proteins Trs85 and Ypt1 to the autophagosome formation site. The Journal of biological chemistry 94 23129774
2012 Charting the landscape of tandem BRCT domain-mediated protein interactions. Science signaling 92 22990118
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2005 Trs85 (Gsg1), a component of the TRAPP complexes, is required for the organization of the preautophagosomal structure during selective autophagy via the Cvt pathway. The Journal of biological chemistry 82 16079147
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2021 Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains. Molecular cell 64 33957083
2011 Organization and assembly of the TRAPPII complex. Traffic (Copenhagen, Denmark) 62 21453443
2015 Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation. Science signaling 61 25921289
2005 Trs85 is required for macroautophagy, pexophagy and cytoplasm to vacuole targeting in Yarrowia lipolytica and Saccharomyces cerevisiae. Autophagy 61 16874038
2011 The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated SEDT and TRAPPC9-associated congenital intellectual disability. PloS one 54 21858081
2014 Identification of conserved, centrosome-targeting ASH domains in TRAPPII complex subunits and TRAPPC8. Cilia 33 25018876
2017 Gsg1, Trnp1, and Tmem215 Mark Subpopulations of Bipolar Interneurons in the Mouse Retina. Investigative ophthalmology & visual science 15 28199486
2013 Identification of TRAPPC8 as a host factor required for human papillomavirus cell entry. PloS one 15 24244674
1995 GSG1, a yeast gene required for sporulation. Yeast (Chichester, England) 11 8619313
2020 Distinct Roles of TRAPPC8 and TRAPPC12 in Ciliogenesis via Their Interactions With OFD1. Frontiers in cell and developmental biology 9 32258032
2023 SP-141 targets Trs85 to inhibit rice blast fungus infection and functions as a potential broad-spectrum antifungal agent. Plant communications 8 37771153
2024 The TRAPPIII subunit, Trs85, has a dual role in the trafficking of cellulose synthase complexes in Arabidopsis. The Plant journal : for cell and molecular biology 4 38402593
2025 TRS85 and LEM3 suppressor mutations rescue stress hypersensitivities caused by lack of structural diversity of complex sphingolipids in budding yeast. The FEBS journal 3 40266832
2025 The TRAPPC8/TRS85 subunit of the Arabidopsis TRAPPIII tethering complex regulates endoplasmic reticulum function and autophagy. Plant physiology 1 40084709