Affinage

USO1

General vesicular transport factor p115 · UniProt O60763

Length
962 aa
Mass
107.9 kDa
Annotated
2026-06-10
18 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

USO1/p115 is a vesicle-tethering factor required for protein transport from the ER to the Golgi apparatus, where its loss causes accumulation of core-glycosylated secretory precursors, ER expansion, and disruption of Golgi structure (PMID:2010462, PMID:23185636). The protein is a homodimer built from two N-terminal globular head domains and a long (~155 nm) coiled-coil tail interrupted by hinge regions, forming an elongated ~800–900 kDa oligomer (PMID:8812994, PMID:8166741). It binds COPII-uncoated ER-derived vesicles in an ATP-dependent manner and physically links separate vesicle populations, acting as a tethering factor (PMID:17192843). Function is genetically and physically coupled to the RAB1/Ypt1 GTPase pathway: the globular head binds RAB1, and RAB1 directs USO1 to early Golgi puncta where it colocalizes with Sed5 and other early-Golgi markers (PMID:8607820, PMID:28973856, PMID:37249218). The essential cellular activity resides in the globular head's regulation of SNAREs rather than in long-range coiled-coil tethering — the head domain binds the SNAREs Bos1 and Bet1 of the Sed5/Bos1/Bet1/Sec22 complex directly, head-domain missense mutations that strengthen SNARE binding bypass the RAB1 requirement, and the monomeric head alone complements loss of USO1 when overexpressed (PMID:37249218). The head domain also binds Sec16A, bridging the early Golgi to ER exit sites to support efficient secretion (PMID:42169630). USO1 is indispensable for Golgi integrity and early mammalian embryonic development (PMID:23185636). Beyond canonical trafficking, USO1 associates with centriolar satellites in male germ cells and supports germ-cell proliferation, cell-cycle progression, and DNA damage repair (PMID:40362515).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1991 High

    Established that USO1 is genetically required for ER-to-Golgi protein transport, defining its core biological role.

    Evidence Temperature-sensitive yeast mutants with invertase precursor accumulation and ER expansion, complementation cloning, EM

    PMID:2010462

    Open questions at the time
    • Molecular mechanism of transport not defined
    • No binding partners identified
    • Coiled-coil function inferred only from sequence
  2. 1994 High

    Mapped the functional requirement to the coiled-coil rod and showed the protein assembles into a large elongated oligomer, indicating a structural/scaffolding architecture.

    Evidence Deletion analysis, uso1-1 amber allele sequencing, gel filtration and sucrose gradient fractionation

    PMID:7706227 PMID:8166741

    Open questions at the time
    • Oligomer subunit stoichiometry not resolved at this stage
    • No direct structural visualization
    • How coiled-coil contributes mechanistically unknown
  3. 1996 High

    Resolved the native architecture as a homodimer with two globular heads and a long hinged coiled-coil tail, establishing the domain layout underlying tethering.

    Evidence Rotary-shadowing EM of purified protein, secondary structure prediction

    PMID:8812994

    Open questions at the time
    • Functional assignment of head versus tail not yet established
    • Binding partners of each domain unknown
  4. 1996 Medium

    Placed USO1 in the Ypt1/RAB1 GTPase transport step through genetic suppression, linking it to vesicle targeting/fusion machinery.

    Evidence Genetic suppression by SLY genes and calcium supplementation in yeast

    PMID:8607820

    Open questions at the time
    • Genetic epistasis only, no direct USO1-Ypt1 binding shown
    • Step (targeting vs fusion) not distinguished
  5. 2007 Medium

    Demonstrated that USO1 directly binds COPII-uncoated ER-derived vesicles and physically tethers vesicle populations, providing biochemical support for a tethering function.

    Evidence In vitro membrane binding/tethering assay, sucrose density block centrifugation, semi-intact cell system

    PMID:17192843

    Open questions at the time
    • Membrane receptor for USO1 binding not identified
    • ATP requirement mechanism unclear
    • Single lab
  6. 2012 High

    Showed USO1 is non-redundant in mammals, being required for Golgi integrity and embryonic viability.

    Evidence Mouse knockout with embryonic lethality and Golgi disruption analysis

    PMID:23185636

    Open questions at the time
    • Molecular cause of lethality not dissected
    • Cell-type-specific requirements unknown
  7. 2017 Medium

    Assigned distinct partners to the two domains — head to Ypt1/RAB1, tail to the SNARE Sed5 — and proposed USO1 as a fidelity factor in vesicle docking.

    Evidence Genetic suppression and domain-function mapping in yeast

    PMID:28973856

    Open questions at the time
    • Interactions inferred from genetics rather than direct binding
    • Tail-Sed5 binding later reframed by head-SNARE data
    • Single lab
  8. 2023 High

    Established that the essential function is SNARE regulation by the globular head, not long-range coiled-coil tethering, redefining the mechanistic model.

    Evidence Genetic suppressor screen (RAB1-null bypass), S-tag co-precipitation and purified-protein binding to Bos1/Bet1, monomeric head complementation, live imaging, AlphaFold2

    PMID:37249218

    Open questions at the time
    • How head binding promotes SNARE assembly/fusion mechanistically not resolved
    • Generality to mammalian p115 not directly tested here
  9. 2025 Medium

    Revealed a non-canonical role for USO1 at centriolar satellites in germ cells affecting proliferation, cell cycle, and DNA repair.

    Evidence CRISPR knockout in germ cell lines with proliferation/apoptosis/cell-cycle/DNA-repair assays, transcriptomics, IF co-localization

    PMID:40362515

    Open questions at the time
    • Mechanistic basis of centriolar satellite association unclear
    • Link to canonical trafficking function not defined
    • Single lab
  10. 2026 High

    Identified a direct p115 head-Sec16A interaction that bridges the early Golgi to ER exit sites, connecting tethering to COPII vesicle biogenesis.

    Evidence Direct binding with purified proteins, deletion mapping, AlphaFold, secretion assays with binding-defective mutants

    PMID:42169630

    Open questions at the time
    • In vivo importance relative to RAB1/SNARE interactions not quantified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the globular head mechanistically couples RAB1 binding, SNARE engagement, and Sec16A bridging into a single fusion-promoting step remains unresolved.
  • No integrated structural model of head-RAB1-SNARE-Sec16A engagement
  • Order of binding events during vesicle docking unknown
  • Connection between trafficking and germ-cell/centriolar roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005794 Golgi apparatus 2 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 1
Partners
BET1BOS1GM130GRASP65RAB1SEC16ASED5

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 USO1 (yeast Uso1p) is required for intracellular protein transport from the ER to the Golgi apparatus; loss-of-function temperature-sensitive mutants accumulate core-glycosylated invertase precursor and show ER expansion with abnormal microtubule bundles. The protein encodes a 1790-aa hydrophilic protein with a C-terminal ~1100-aa coiled-coil domain characteristic of cytoskeletal proteins. Temperature-sensitive mutant characterization, complementation cloning, protein secretion assay (invertase processing), electron microscopy, DNA sequence analysis The Journal of cell biology High 2010462
1994 The coiled-coil rod region of Uso1 is essential for protein transport from the ER to the Golgi at restrictive temperature; the uso1-1 amber mutation at codon 951 truncates the coiled-coil and is temperature-sensitive. Uso1 protein forms a nonglobular high-molecular-mass complex (~800–900 kDa by gel filtration) consistent with an oligomeric structure. Deletion analysis of USO1, sequencing of uso1-1 allele, gel filtration, sucrose density gradient centrifugation, Western blot Journal of biochemistry High 7706227 8166741
1994 Uso1 protein is predominantly soluble and forms a nonglobular oligomer of ~800–900 kDa as assessed by gel filtration, but sediments with a 6S marker in sucrose gradients, indicating an elongated rather than globular native structure. Gel filtration chromatography, sucrose density gradient centrifugation, Western blot with anti-Uso1 antibodies Biochemical and biophysical research communications Medium 8166741
1996 Uso1 protein is a homodimer with two globular head domains and a long (~154.5 nm) coiled-coil tail with hinge regions at ~23.1 nm and ~85.5 nm from the globular domain, as directly visualized by electron microscopy of purified protein. Purification to homogeneity, rotary-shadowing electron microscopy, secondary structure prediction Journal of structural biology High 8812994
1996 The temperature-sensitive secretion defect of uso1-1 is suppressed by elevated calcium in the medium or by introduction of SLY genes (suppressors of ypt1 defects), placing Uso1 in the same transport step as Ypt1 (a small GTPase), suggesting they function together in targeting or fusion of transport vesicles to the Golgi membrane. Genetic suppression analysis, calcium supplementation, multicopy suppressor (SLY gene introduction) Biochemical and biophysical research communications Medium 8607820
2007 Uso1 binds specifically to COPII-uncoated ER-derived vesicles in vitro; this binding is ATP-dependent, does not require the C-terminal acidic region of Uso1, and enables physical linkage (tethering) of separate vesicle populations. Binding was detected by sucrose density block centrifugation of purified Uso1 with membrane fractions. In vitro membrane binding assay, sucrose density block centrifugation, semi-intact cell transport system, biochemical fractionation Journal of cellular biochemistry Medium 17192843
2012 USO1 is indispensable for early embryonic development in mice; homozygous knockout results in early embryonic lethality accompanied by disruption of Golgi structure, indicating that unlike some other golgins, USO1 cannot be functionally compensated by other family members in vivo. Mouse knockout (gene targeting), histological and immunofluorescence analysis of Golgi structure in embryos PloS one High 23185636
2017 The globular head of Uso1 binds to Ypt1 (Rab1 GTPase) and the coiled-coil tail binds to the Golgi SNARE Sed5. Inappropriate recruitment of Uso1 to secretory vesicles via ectopic Ypt1 activity blocks docking to the plasma membrane, suggesting Uso1 acts as a fidelity factor in vesicle docking through these two interactions. Genetic suppression analysis (truncation of Uso1 suppresses toxicity), yeast secretion assays, domain function mapping Proceedings of the National Academy of Sciences of the United States of America Medium 28973856
2021 USO1-T isoform (lacking ARM10 loop encoded by exon 15) promotes Golgi unstacking and accelerates ER-to-Golgi and Golgi-to-plasma-membrane vesicle trafficking; ERK and GRASP65 are involved in USO1-T-mediated Golgi dysfunction. Structural modeling predicts that the missing ARM10 loop weakens dimerization and tethering to GM130. RNA-seq isoform profiling, overexpression in liver cancer cells, in vitro and in vivo functional assays, Golgi morphology imaging, structural modeling, ERK/GRASP65 pathway analysis Carcinogenesis Medium 34293111
2023 The globular head domain (GHD) of Uso1 directly binds SNAREs Bos1 and Bet1 of the Sed5/Bos1/Bet1/Sec22 SNARE complex, as shown by S-tag co-precipitation and direct binding assays with purified proteins. GHD missense mutations (E6K, G540S) that bypass the requirement for RAB1 show stronger Bos1 binding. The GHD monomer (without coiled-coil/CTR dimerization domain) can complement uso1Δ when overexpressed, indicating that long-range tethering is dispensable and that the essential Uso1 function involves SNARE regulation. Uso1 localizes to early Golgi puncta (60 s half-life) colocalizing with RAB1, Sed5, GeaA, and Rer1; this localization depends on RAB1. Genetic suppressor screen (rab1-null rescue by uso1 missense mutations), S-tag co-precipitation, purified protein binding assays, live-cell imaging (fluorescence microscopy, half-life measurement), complementation assay, AlphaFold2 structural prediction eLife High 37249218
2025 USO1 is associated with centriolar satellites (CSs) in male germ cells; Uso1 knockout in GC1 and GC2 germ cell lines suppresses cell proliferation, stimulates apoptosis, blocks cell cycle progression, and weakens DNA damage repair, revealing a role for USO1 in spermatogenesis-related gene regulation beyond canonical ER-Golgi trafficking. CRISPR knockout of Uso1 in germ cell lines, cell proliferation/apoptosis assays, cell cycle analysis, DNA damage repair assays, transcriptomic analysis, immunofluorescence co-localization with centriolar satellite markers International journal of molecular sciences Medium 40362515
2026 The head domain of human p115 (USO1) binds directly to Sec16A, a scaffolding protein that organises ER exit sites and promotes COPII vesicle formation. Structural prediction and deletion mapping identify the interaction site as a conserved motif in the unstructured N-terminal region of Sec16A. Mutations in p115 that block this interaction reduce the efficiency of secretion, suggesting p115 bridges the early Golgi to ER exit sites. Direct binding assay (purified proteins), deletion mapping, structural prediction (AlphaFold), secretion efficiency assay with p115 binding-defective mutants Journal of cell science High 42169630

Source papers

Stage 0 corpus · 18 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 A cytoskeleton-related gene, uso1, is required for intracellular protein transport in Saccharomyces cerevisiae. The Journal of cell biology 153 2010462
1996 Uso1 protein is a dimer with two globular heads and a long coiled-coil tail. Journal of structural biology 65 8812994
2021 Focused CRISPR-Cas9 genetic screening reveals USO1 as a vulnerability in B-cell acute lymphoblastic leukemia. Scientific reports 18 34162911
2015 Lentivirus-mediated silencing of USO1 inhibits cell proliferation and migration of human colon cancer cells. Medical oncology (Northwood, London, England) 18 26184508
2017 Rewiring a Rab regulatory network reveals a possible inhibitory role for the vesicle tether, Uso1. Proceedings of the National Academy of Sciences of the United States of America 17 28973856
2016 USO1 promotes tumor progression via activating Erk pathway in multiple myeloma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 15 26898451
1994 Uso1 protein contains a coiled-coil rod region essential for protein transport from the ER to the Golgi apparatus in Saccharomyces cerevisiae. Journal of biochemistry 15 7706227
1994 Molecular characterization of the USO1 gene product which is essential for vesicular transport in Saccharomyces cerevisiae. Biochemical and biophysical research communications 15 8166741
2007 Specific membrane recruitment of Uso1 protein, the essential endoplasmic reticulum-to-Golgi tethering factor in yeast vesicular transport. Journal of cellular biochemistry 12 17192843
2012 Golgi disruption and early embryonic lethality in mice lacking USO1. PloS one 11 23185636
2021 USO1 isoforms differentially promote liver cancer progression by dysregulating the ER-Golgi network. Carcinogenesis 9 34293111
2023 The Uso1 globular head interacts with SNAREs to maintain viability even in the absence of the coiled-coil domain. eLife 8 37249218
2022 USO1 expression is dysregulated in non-small cell lung cancer. Translational lung cancer research 7 36248341
1996 Calcium and SLY genes suppress the temperature-sensitive secretion defect of Saccharomyces cerevisiae uso1 mutant. Biochemical and biophysical research communications 7 8607820
2021 A novel all-trans retinoic acid derivative regulates cell cycle and differentiation of myelodysplastic syndrome cells by USO1. European journal of pharmacology 5 34058203
1996 Physical mapping of a centromere-proximal region of chromosome IV-L defines the placement of genes USO1, MBP1, PSA1 and SLC1. Yeast (Chichester, England) 2 8701613
2026 The Golgi vesicle tether p115/USO1 can bind directly to the ER exit site organiser Sec16A. Journal of cell science 0 42169630
2025 USO1 Coordinates Centriolar Satellites to Regulate Male Germ Cell Proliferation and Cell Cycle Progression. International journal of molecular sciences 0 40362515

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