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Human USO1/p115 is a conserved ERGIC/cis-Golgi vesicle tether/fusion factor in
the early secretory pathway, connecting Rab1-regulated COPII vesicle capture and
docking with SNARE-dependent membrane fusion.
"Human **USO1/p115** is a conserved **ERGIC/cis-Golgi vesicle tether/fusion factor** in early secretory trafficking, connecting Rab1-regulated vesicle capture/docking with SNARE-dependent membrane fusion."
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p115/USO1 is described as a Golgi vesicle tethering protein that promotes vesicle
docking and fusion, in part through binding to SNARE machinery and Rab GTPase-dependent
recruitment.
"p115/USO1 is described as a **Golgi vesicle tethering protein** that promotes **vesicle docking and fusion**, in part through binding to SNARE machinery and Rab GTPase–dependent recruitment."
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Rab1 (RAB1A/B) on COPII vesicles recruits p115/USO1 at the ER-Golgi interface, and
p115 then helps organize or stabilize cis-Golgi SNARE complex assembly. p115 interacts
with Rab1A via its N-terminus and with cis-Golgi SNAREs (Sec22b, Bet1, GOSR2, syntaxin-5).
"A widely used framework is that **Rab1 (RAB1A/B)** on COPII vesicles recruits p115/USO1 at the ER–Golgi interface, and p115 then helps organize or stabilize **cis-Golgi SNARE complex assembly**, promoting membrane fusion. A 2023 thesis synthesis explicitly states that p115 has been shown to interact with **Rab1A via its N-terminus** and that p115 interacts with cis-Golgi SNAREs (e.g., Sec22b, Bet1, GOSR2, syntaxin-5) in proposed fusion models."
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GM130 binds p115 at its N-terminus, and this interaction can be blocked by Cdk1
phosphorylation of GM130 Ser37 during mitosis, consistent with mitotic reorganization
of the Golgi.
"A 2023 thesis synthesis states that **GM130 binds p115 at its N-terminus** and that this interaction can be blocked by **Cdk1 phosphorylation of GM130 S37** during mitosis, consistent with mitotic reorganization of the Golgi."
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A human-cell study reports that the p115 head domain can bind directly to Sec16A,
an ER exit-site organiser, with mutations that disrupt motif binding reducing secretion
efficiency, linking a Golgi tether to ER exit-site scaffolding.
"A human-cell study reports that the p115 head domain can bind directly to Sec16A, with mutations that disrupt motif binding reducing secretion efficiency, providing a mechanistic link between a Golgi tether and ER exit-site scaffolding."
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Human p115/USO1 localizes to the ERGIC and cis-Golgi, associates with Golgi membranes
in a Rab1-dependent manner, cycles on/off membranes, and functions at the ER-Golgi
interface at early secretory trafficking steps.
"Human p115/USO1 localizes to the **ERGIC and cis-Golgi**, cycling on/off membranes and acting at early secretory trafficking steps. A human-cell study describes p115 as anchored to Golgi membranes, acting at the ER–Golgi interface, and adds functional coupling to ER exit sites via binding to Sec16A."
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Homolog (fungal Uso1) work shows the globular head domain directly binds SNAREs
(including Bet1 and Bos1/membrin family members) and that a monomeric head domain
can complement loss of full-length Uso1 in vivo, arguing the essential role can
involve direct regulation of SNARE machinery rather than long-range coiled-coil tethering.
"A 2023 eLife study (fungal Uso1; homolog of human p115) reports that the **globular head domain directly binds SNAREs** (including Bet1 and Bos1/membrin family members) and that a **monomeric head domain** can complement loss of full-length Uso1 in vivo when overexpressed—arguing that long-range coiled-coil tethering can be dispensable and that the essential role can involve **direct regulation of SNARE machinery**."
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Structural evidence (largely from yeast/fungal homologs) shows an N-terminal globular
head with armadillo-repeat/alpha-solenoid architecture and a long coiled-coil tail;
human-focused studies describe p115 as a dimer with an N-terminal head and coiled-coil tail.
"yeast/fungal Uso1/p115 head domains adopt an **armadillo-repeat/alpha-solenoid** organization, and the protein includes long coiled-coils implicated in tethering-distance/geometry. Human-centric sources in this set largely describe p115 as a **dimer with an N-terminal head and coiled-coil tail**."
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The Legionella effector LegA15 hijacks host p115, inducing host Golgi fragmentation
and altering lipid-droplet homeostasis; proteomics identified p115/USO1 as a top
putative interactor with 62 unique peptides.
"a 2022 Science Advances study shows that the Legionella effector **LegA15** hijacks host **p115**, inducing host **Golgi fragmentation** and altering lipid-droplet homeostasis. Proteomics identified p115/USO1 as a top putative interactor with high peptide support"
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In hepatocellular carcinoma, a tumor-associated isoform USO1-T correlates with poorer
prognosis, causes Golgi unstacking, and accelerates ER-to-Golgi/plasma membrane
trafficking, with modeling implicating weakened dimerization/GM130 tethering, ERK and GRASP65.
"in human HCC, a tumor-associated isoform **USO1-T** correlates with poorer prognosis, promotes aggressive behavior, causes **Golgi unstacking**, and accelerates trafficking from ER to Golgi/plasma membrane; modeling suggests weakened dimerization/GM130 tethering and involvement of **ERK** and **GRASP65**."
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A 2024 RA synovial phosphoproteomics study reported USO1 Ser48 as the phosphosite
with the highest inverse correlation with ESR, indicating regulated USO1 phosphorylation
in human disease tissue (associative, not mechanistically assigned to trafficking).
"A 2024 phosphoproteomics/proteomics study of **treatment-naive RA synovial biopsies (n=8)** reports that **USO1 Ser48** was the phosphosite with the **highest inverse correlation with ESR** in their analysis, illustrating that USO1 is phosphorylated in human inflammatory tissue and that specific phosphosites can correlate with clinical measures."