Affinage

OSBP

Oxysterol-binding protein 1 · UniProt P22059

Length
807 aa
Mass
89.4 kDa
Annotated
2026-04-29
96 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OSBP is a lipid transfer protein that operates at ER–trans-Golgi network membrane contact sites to execute a thermodynamically coupled cycle of cholesterol/PI(4)P counter-exchange: its PH domain binds Golgi PI4P and its FFAT motif engages ER-resident VAP-A to tether opposing membranes, while the ORD domain shuttles cholesterol from ER to Golgi and back-transfers PI(4)P to the ER for hydrolysis by Sac1, making the cycle irreversible and driving net sterol delivery (PMID:24209621, PMID:34103503). This activity makes OSBP a major determinant of Golgi PI4P homeostasis and lipid order along the secretory pathway, controlling intra-Golgi SNARE localization, retrograde trafficking, sphingomyelin synthesis, and insulin granule maturation (PMID:28978670, PMID:24048449, PMID:9806908, PMID:38536815). Beyond lipid transfer, OSBP functions as a cholesterol-regulated scaffold that assembles a PP2A/HePTP phosphatase complex to dephosphorylate ERK1/2 (PMID:15746430), and is co-opted by positive-strand RNA viruses and intracellular bacteria to supply cholesterol to replication organelles and pathogen-containing vacuoles (PMID:29367253, PMID:31091452).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Early work established that OSBP is a sterol-responsive protein whose phosphorylation state and Golgi/cytoplasm partitioning are controlled by cellular cholesterol levels, and that Golgi-localized OSBP stimulates ceramide-to-sphingomyelin conversion, providing the first functional link between OSBP and Golgi lipid metabolism.

    Evidence Subcellular fractionation and metabolic labeling in cholesterol-manipulated CHO cells

    PMID:9806908 PMID:9869656

    Open questions at the time
    • Mechanism by which OSBP promotes sphingomyelin synthesis was not identified
    • Whether OSBP directly transports sterols was unknown
  2. 2005 High

    Structural determination of the yeast ORD domain revealed a single-sterol hydrophobic tunnel with a conformational lid, providing the first atomic model for how OSBP-family proteins extract and shield a sterol during intermembrane transfer.

    Evidence X-ray crystallography (1.5–2.5 Å) of Osh4 with ergosterol, cholesterol, and oxysterols

    PMID:16136145

    Open questions at the time
    • Counter-transport of a second lipid (PI4P) was not yet recognized
    • How the lid opening/closing couples to membrane docking was unresolved
  3. 2005 High

    Discovery that OSBP functions as a cholesterol-regulated scaffold for PP2A and HePTP to control ERK1/2 phosphorylation established a signaling role for OSBP independent of lipid transfer.

    Evidence Reciprocal co-immunoprecipitation, cholesterol depletion, phosphatase activity assays

    PMID:15746430

    Open questions at the time
    • How cholesterol binding regulates scaffold assembly at the structural level is unknown
    • Whether OSBP's signaling and lipid transfer functions are coordinated was not tested
  4. 2007 High

    Systematic domain mapping resolved the sterol-binding command center (aa 408–459), the HePTP- and PP2A-binding C-terminal regions, and the cooperative role of the N-terminal disordered region in cholesterol recognition, establishing a modular architecture for OSBP.

    Evidence Truncation mapping, Y458S mutagenesis, in vitro binding assays

    PMID:18165705

    Open questions at the time
    • Structural basis for cooperative N-terminal contribution to cholesterol binding was not determined
    • How scaffolding and lipid transfer domains interact in full-length OSBP was unclear
  5. 2008 Medium

    Multiple studies broadened OSBP's functional reach: it destabilizes ABCA1 protein via its sterol-binding domain (regulating cholesterol efflux), participates in 7-ketocholesterol-stimulated JAK2-STAT3 signaling, and modulates amyloidogenic APP processing via Golgi-dependent sterol sensing.

    Evidence RNAi, ABCA1 half-life measurement, JAK2 inhibition, APP processing assays

    PMID:18230613 PMID:18348724 PMID:18450749

    Open questions at the time
    • Mechanism linking OSBP sterol-binding to ABCA1 degradation machinery is uncharacterized
    • APP and JAK2-STAT3 findings are each from single labs and await independent replication
    • Whether these effects reflect lipid transfer versus scaffolding remains ambiguous
  6. 2010 High

    Drosophila genetic analysis demonstrated that OSBP-mediated sterol transport is required for membrane remodeling during spermatid individualization, revealing a conserved developmental role.

    Evidence Drosophila Osbp mutants, dietary sterol rescue, co-IP with VAP-family protein FAN

    PMID:20943709

    Open questions at the time
    • Whether the mammalian ortholog has a comparable role in mammalian spermatogenesis is untested
    • PI4P counter-transport was not evaluated in this context
  7. 2013 High

    The full cholesterol/PI(4)P counter-exchange cycle was reconstituted in vitro, establishing that OSBP tethers ER and Golgi membranes, transfers sterol one direction and PI4P the other, with Sac1-mediated PI4P hydrolysis providing thermodynamic irreversibility — the central mechanistic model for OSBP function.

    Evidence Liposome reconstitution with purified proteins, fluorescent lipid transfer assays, domain mutagenesis

    PMID:24209621

    Open questions at the time
    • Kinetic parameters for PI4P versus sterol transfer in cellulo were not measured
    • Stoichiometry and regulation of the cycle by phosphorylation remained unresolved
  8. 2013 High

    OSBP depletion mislocalized intra-Golgi v-SNAREs GS28 and GS15 in a manner requiring all three functional domains; epistasis with ArfGAP1 implicated COPI vesicle transport, linking OSBP's sterol/PI4P transfer to Golgi trafficking machinery.

    Evidence siRNA knockdown, immunofluorescence, double-knockdown epistasis with ArfGAP1

    PMID:24048449

    Open questions at the time
    • Whether cholesterol or PI4P depletion is the proximal cause of SNARE mislocalization was not dissected
    • Direct interaction between OSBP and COPI components was not tested
  9. 2017 High

    Quantitative cellular studies established that endogenous OSBP accounts for roughly half of total PI4P consumption and is coupled with PI4KIIIβ and PI4KIIα to establish the lipid order gradient along the secretory pathway; structural work on yeast Osh1 confirmed competitive PI4P/sterol binding in the same pocket.

    Evidence OSW-1 pharmacological inhibition with live-cell lipid sensors; X-ray crystallography of Osh1 ORD with ergosterol and PI4P

    PMID:28319008 PMID:28978670

    Open questions at the time
    • How OSBP activity is dynamically coordinated with PI4-kinase activity in real time is unresolved
    • Whether other ORP family members compensate when OSBP is inhibited long-term was not fully explored
  10. 2018 High

    OSBP was identified as an obligate host factor hijacked by Aichi virus: viral proteins directly recruit OSBP to replication organelles to supply cholesterol via the VAP-A/Sac1-dependent counter-exchange cycle, establishing OSBP as a broad antiviral target.

    Evidence Co-IP with viral 2B/2BC/2C/3A/3AB, siRNA, cholesterol imaging at viral replication sites

    PMID:29367253

    Open questions at the time
    • Whether OSBP's PI4P-independent recruitment to viral organelles uses the same ORD transfer mechanism was not demonstrated
    • Structural basis for OSBP interaction with diverse viral proteins is unknown
  11. 2019 High

    The intrinsically disordered N-terminal Gly-Pro-Ala-rich region was shown to act as an entropic barrier preventing homotypic Golgi–Golgi tethering while promoting OSBP recycling at ER–Golgi contact sites, and Salmonella effector SseL was found to recruit OSBP to pathogen-containing vacuoles for membrane maintenance.

    Evidence Liposome reconstitution with FRAP for N-terminal function; Co-IP and siRNA for Salmonella SseL–OSBP interaction

    PMID:30905771 PMID:31091452

    Open questions at the time
    • How phosphorylation of the disordered N-terminal region modulates its entropic barrier function is unknown
    • Whether OSBP transfers cholesterol to Salmonella vacuoles via the canonical PI4P counter-exchange is not established
  12. 2021 High

    Cryo-electron tomography of reconstituted VAP-A/OSBP membrane contact sites revealed the T-shaped dimeric architecture of OSBP, showing how VAP-A flexibility accommodates variable intermembrane distances and how the two ORD domains shuttle between opposing membranes.

    Evidence Cryo-ET of in vitro reconstituted two-membrane contact sites

    PMID:34103503

    Open questions at the time
    • A high-resolution structure of full-length human OSBP is still lacking
    • How T-shaped geometry changes upon sterol/PI4P loading was not captured
  13. 2022 High

    The crystal structure of the human OSBP ORD bound to cholesterol defined the hydrogen-bond network anchoring the sterol hydroxyl and identified critical tunnel residues (M446, L590) required for viral replication support.

    Evidence X-ray crystallography of human OSBP ORD–cholesterol complex; mutagenesis with enterovirus replication assay

    PMID:35613096

    Open questions at the time
    • A co-crystal structure with PI4P for human OSBP ORD is not yet available
    • How the lid mechanism operates in the full-length human dimer is unresolved
  14. 2024 High

    Multiple studies in 2024 demonstrated that OSBP is recruited to ER–insulin secretory granule contact sites in a Ca²⁺- and PI4P-dependent manner to support glucose-stimulated insulin secretion, confirmed OSBP as the major Golgi PI4P homeostatic regulator, and identified selective OSBP inhibitors (oxybipins, orpinolide) that block retrograde trafficking and exploit cholesterol transport dependency in leukemia.

    Evidence Live-cell imaging with acute inhibition and siRNA in β-cells; PI4P biosensors with genetic manipulations; thermal proteome profiling and CRISPR screens for drug target identification

    PMID:38107113 PMID:38405037 PMID:38536815 PMID:38907112

    Open questions at the time
    • Whether OSBP inhibition selectively kills leukemia cells over normal hematopoietic cells in vivo is untested
    • Structural basis for selective OSBP inhibition by oxybipins versus other ORPs is not determined
    • Whether Ca²⁺-dependent OSBP recruitment to granules involves a direct calcium sensor or an intermediary is unresolved
  15. 2025 Medium

    Under oxidative stress OSBP protein levels decline in neurons, causing lysosomal PI4P accumulation and disrupted anterograde lysosomal transport; OSBP overexpression rescues PI4P/PI3P balance and axonal repair, extending OSBP's lipid-homeostatic role to neuronal injury.

    Evidence H₂O₂ neuronal model, AAV-mediated OSBP overexpression in TBI mouse model, PI4P/PI3P imaging

    PMID:39915357

    Open questions at the time
    • Single-lab study; independent replication is needed
    • Whether OSBP acts directly on lysosomes or indirectly via Golgi PI4P depletion is unclear
    • Mechanism of oxidative stress-induced OSBP degradation is not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of full-length dimeric human OSBP, how phosphorylation dynamically regulates the transfer cycle in cells, whether OSBP's scaffolding (ERK signaling) and lipid transfer functions are mechanistically coupled, and the therapeutic window for OSBP inhibitors in cancer and viral infection.
  • No full-length human OSBP structure exists
  • Phosphoregulation of the counter-exchange cycle is poorly understood
  • Coupling between scaffolding and lipid transfer activities has not been tested
  • In vivo therapeutic index for OSBP inhibitors is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0140104 molecular carrier activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005794 Golgi apparatus 6 GO:0005783 endoplasmic reticulum 3 GO:0031410 cytoplasmic vesicle 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
ACBD3PI4KBPPP2CAPTPN7SACM1LVAPAVAPB
Complex memberships
OSBP/PP2A/HePTP phosphatase scaffoldOSBP/VAP-A ER-Golgi tethering complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 OSBP drives cholesterol/PI(4)P counter-exchange between ER and Golgi through a four-step cycle: (1) membrane tethering via PH domain (Golgi PI4P) and FFAT motif (ER VAP-A); (2) sterol transfer from ER to Golgi by the ORD domain; (3) back-transfer of PI(4)P from Golgi to ER by the ORD domain; (4) PI(4)P hydrolysis by the ER phosphatase Sac1, which provides thermodynamic driving force for net sterol transport. In vitro reconstitution with liposomes, lipid transfer assays, fluorescence microscopy, domain mutagenesis Cell High 24209621
2005 The ORD (OSBP-related domain) of yeast Osh4 (OSBP ortholog) contains a hydrophobic tunnel that binds a single sterol molecule; a flexible N-terminal lid closes upon sterol binding, stabilizing a transport-competent conformation; basic residues at the tunnel entrance are critical for function; an open-lid structure reveals phospholipid-binding sites for membrane docking. X-ray crystallography (1.5–2.5 Å resolution) in complex with ergosterol, cholesterol, and hydroxycholesterols; limited proteolysis Nature High 16136145
2005 OSBP functions as a cholesterol-regulated scaffolding protein that forms an ~440 kDa oligomeric complex with PP2A (serine/threonine phosphatase) and HePTP (tyrosine phosphatase) to dephosphorylate ERK1/2; cholesterol depletion or oxysterol addition disassembles the complex and increases pERK levels. Co-immunoprecipitation, biochemical fractionation, cholesterol depletion with methyl-β-cyclodextrin, OSBP overexpression Science High 15746430
2007 The sterol-binding command center of OSBP maps to a centrally located 51-aa region (408–459) that binds both cholesterol and 25-hydroxycholesterol; Y458S mutation impairs binding. HePTP binds OSBP via a C-terminal coiled-coil domain (732–761) and PP2A binds a separate C-terminal region. An N-terminal Gly-Ala-rich region cooperates with the PH domain to control cholesterol (but not 25-OHC) binding. Domain truncation mapping, point mutagenesis (Y458S), in vitro binding assays, co-immunoprecipitation The Journal of biological chemistry High 18165705
2017 Endogenous OSBP activity accounts for approximately half of total cellular PI4P consumption; blocking OSBP with OSW-1 causes sterol accumulation at the ER/lipid droplets at the expense of the trans-Golgi network, reducing the lipid order gradient along the secretory pathway; OSBP couples spatiotemporally with PI4KIIIβ and PI4KIIα to control organelle lipid composition. Pharmacological inhibition (OSW-1), live-cell fluorescence imaging (lipid order sensors), PI4P metabolic labeling, electron microscopy The EMBO journal High 28978670
1998 Cholesterol levels regulate OSBP phosphorylation state and its shuttling between cytoplasm/vesicular compartments and the Golgi apparatus; cholesterol depletion causes OSBP dephosphorylation and constitutive Golgi localization; 25-hydroxycholesterol stimulates sphingomyelin synthesis in a manner correlated with OSBP phosphorylation and Golgi localization. Subcellular fractionation, immunofluorescence, cholesterol manipulation (LDL supplementation, lovastatin), [³H]serine incorporation into sphingomyelin The Biochemical journal High 9806908
1999 OSBP overexpression potentiates 25-hydroxycholesterol-stimulated sphingomyelin synthesis (>8.5-fold vs. 3.5-fold in controls); 25-hydroxycholesterol promotes OSBP translocation to the Golgi where it stimulates ceramide-to-sphingomyelin conversion; diacylglycerol mass is reduced in Golgi fractions from overexpressing cells. [³H]serine and [³H]sphinganine labeling, Golgi fractionation, in vitro enzyme assays, OSBP overexpression in CHO cells Journal of lipid research Medium 9869656
2008 OSBP negatively regulates ABCA1 protein stability via its sterol-binding domain; OSBP knockdown increases ABCA1 protein half-life ~3-fold and increases cholesterol efflux without affecting ABCA1 mRNA levels; a sterol-binding domain mutation in OSBP abolishes destabilization of ABCA1, whereas Golgi/ER targeting mutations do not. RNAi knockdown, ABCA1 protein half-life measurement, cholesterol efflux assay, domain mutagenesis, LXR agonist treatments The Journal of biological chemistry High 18450749
2008 7-ketocholesterol stimulates OSBP1 tyrosine-394 phosphorylation, which activates JAK2-STAT3 signaling to upregulate profilin-1 gene expression in endothelial cells; this pathway requires OSBP1 as an intermediary between oxysterol signaling and STAT3 activation. Luciferase reporter assays, JAK2 inhibition, phosphorylation site identification, co-immunoprecipitation, diabetic rat aorta validation The Journal of biological chemistry Medium 18230613
2019 A long (~90 aa) intrinsically disordered Gly-Pro-Ala-rich N-terminal sequence of OSBP acts as an entropic barrier that prevents homotypic tethering of two Golgi-like membranes by OSBP PH domains, facilitates OSBP in-plane diffusion, and promotes recycling at ER-Golgi membrane contact sites; removal of this region increases protein density at MCS and impairs OSBP dynamics. In vitro reconstitution with liposomes, FRAP, fluorescence microscopy, hydrodynamic radius measurements, domain truncation Developmental cell High 30905771
2021 Cryo-tomography of an in vitro membrane contact site reconstituted with VAP-A and OSBP reveals that VAP-A is highly flexible (enabling MCS of variable intermembrane distances) and OSBP dimer forms a central T-shaped helical structure; the T-geometry facilitates movement of the two lipid-transfer ORD domains between opposing membranes. Cryo-electron tomography, in vitro MCS reconstitution with two membranes, structural modeling Nature communications High 34103503
2013 OSBP is required for perinuclear localization of intra-Golgi v-SNAREs GS28 and GS15; OSBP depletion by siRNA mislocalizes these SNAREs and reduces Golgi mannosidase II abundance; all three functional domains (ER-targeting, Golgi-targeting, and sterol-binding) are necessary; cholesterol depletion phenocopies OSBP loss; ArfGAP1 co-depletion rescues v-SNARE mislocalization, implicating COPI vesicle transport. siRNA knockdown, immunofluorescence, domain mutagenesis, cholesterol depletion, double-knockdown epistasis (OSBP + ArfGAP1) Molecular biology of the cell High 24048449
2018 OSBP is directly recruited to Aichi virus RNA replication organelles via protein-protein interactions with viral proteins (2B, 2BC, 2C, 3A, 3AB) and ACBD3, independently of PI4P; OSBP, VAP-A/B, and Sac1 are all essential for AiV replication; OSBP-mediated cholesterol transfer supplies cholesterol to viral replication sites; these interactions form membrane contact sites between ER and replication organelles. Co-immunoprecipitation, siRNA knockdown, cholesterol imaging, electron microscopy, viral replication assays Journal of virology High 29367253
2022 Crystal structure of the lipid transfer domain (ORD) of human OSBP in complex with endogenous cholesterol reveals that the hydrocarbon tail and tetracyclic ring interact with the hydrophobic tunnel and the hydroxyl group forms a hydrogen-bond network at the tunnel bottom; systematic mutagenesis (M446W, L590W) identifies residues critical for ligand binding and viral replication support. X-ray crystallography, site-directed mutagenesis, enterovirus replication rescue assay ACS infectious diseases High 35613096
2024 OSBP is recruited to ER-insulin secretory granule contact sites in a Ca²⁺-dependent manner; PI4-kinases positively and the PI4P phosphatase Sac2 negatively regulate OSBP binding to granules; OSBP mediates PI(4)P-cholesterol exchange at these sites; acute inhibition or siRNA knockdown of OSBP suppresses glucose-stimulated insulin secretion without affecting insulin production or Ca²⁺ signaling. Live-cell imaging, OSBP inhibitors (acute), siRNA knockdown, Sac2 knockout, PI4P and cholesterol measurements at granules, insulin secretion assay Cell reports High 38536815
2024 Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in Golgi PI4P levels; OSBP has high capacity for PI4P turnover at orthogonal organelle membranes but does not impact plasma membrane PI4P levels; OSBP is a major determinant of Golgi PI4P homeostasis. Acute and chronic genetic manipulations (overexpression, knockdown), PI4P biosensors, orthogonal OSBP targeting Contact (Thousand Oaks) High 38405037
2024 OSBP inhibition by oxybipins blocks retrograde trafficking (Shiga toxin pathway) and induces partial Golgi degradation via lysosomes with changes in protein glycosylation; oxybipins selectively inhibit OSBP over other sterol transport proteins and stabilize OSBP in intact cells. Biophysical assay panel for sterol transfer proteins, Shiga toxin trafficking assay, glycosylation analysis, thermal proteome profiling, lysosomal degradation assay Nature chemical biology High 38907112
2024 Orpinolide disrupts Golgi homeostasis via a mechanism requiring active PI4P signaling at the ER-Golgi interface; thermal proteome profiling and CRISPR screens identify OSBP as the direct and phenotypically relevant target; orpinolide exploits a cholesterol transport dependency in leukemia cells. Thermal proteome profiling, genome-scale CRISPR-Cas9 screens, multiomics profiling, genetic validation Nature chemical biology High 38107113
2010 In Drosophila, OSBP functions at the leading edge of the individualization complex during spermatogenesis, where it colocalizes with sterol-enriched speckles; OSBP genetically and physically interacts with the testis-specific VAP family protein FAN; dietary sterol supplementation partially rescues Osbp mutant male sterility, establishing a sterol-transport function in membrane remodeling during spermatid individualization. Drosophila genetics (mutant analysis), genetic epistasis, co-immunoprecipitation, sterol dietary rescue, immunofluorescence Development High 20943709
2018 OSBP acts upstream of ABC transporters ABCG1 and ABCA1 to supply cholesterol for insulin granule formation in pancreatic β-cells; OSBP knockdown destabilizes newly made insulin granules and reduces glucose-stimulated insulin secretion; exogenous cholesterol does not rescue OSBP knockdown (unlike ABC transporter knockdown), placing OSBP proximally at the ER; dual knockdown supports serial function. RNAi knockdown (single and double), live-cell imaging, insulin secretion assay, proinsulin synthesis measurement Molecular biology of the cell Medium 29540530
2005 OSBP knockdown by siRNA (~90% reduction) does not affect 25-hydroxycholesterol-induced inhibition of cholesterol biosynthesis gene transcription (HMG-CoA reductase, squalene epoxidase), demonstrating that OSBP is dispensable for sterol-regulated gene suppression. siRNA knockdown, sterol-regulated gene expression by RT-PCR, immunofluorescence of Golgi localization Genes to cells Medium 16098143
2019 Salmonella SseL effector binds the N-terminus of OSBP1 and, together with SseJ, recruits OSBP1 to the Salmonella-containing vacuole in a SPI-2 TTSS-dependent manner; knockdown of OSBP1 or VAPA/B reduces vacuolar integrity and increases bacteria released into the cytoplasm, demonstrating OSBP1 is required for vacuolar membrane stability during intracellular Salmonella replication. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, vacuolar integrity assay Cell reports High 31091452
2008 OSBP1 overexpression downregulates amyloidogenic processing of APP and causes accumulation of APP-Notch2 dimers in the Golgi; OSBP1 knockdown has the opposite effect; 25-hydroxycholesterol treatment reverses Golgi accumulation, linking OSBP1's sterol-sensing function to APP trafficking. Overexpression and siRNA knockdown, APP processing assays (Aβ measurement), co-immunoprecipitation, immunofluorescence Molecular neurodegeneration Medium 18348724
2025 Under oxidative stress, OSBP protein levels decrease in neurons, causing lysosomal PI(4)P accumulation, reduced Arl8 binding to lysosomes, and disrupted anterograde lysosomal transport; OSBP overexpression restores PI(4)P/PI(3)P balance, promotes Arl8 binding, normalizes lysosome distribution in neurites, and improves axonal repair in a TBI mouse model. H2O2 neuronal model, protein-liposome binding assay, AAV-mediated OSBP overexpression in vivo, PI4P/PI3P imaging, lysosome tracking Molecular neurobiology Medium 39915357
2017 Crystal structure of yeast Osh1 ORD in complex with ergosterol and PI(4)P shows these two lipids bind competitively in the same hydrophobic pocket, with ergosterol in a head-down orientation; the PI4P-binding site is structurally conserved; Osh1 ANK domain binds a cytosolic helical segment of Nvj1 for NVJ targeting. X-ray crystallography, competitive binding assays, structure-function analysis Structure High 28319008
2021 Crystal structure of human ORP3 ORD in apo-form and in complex with PI(4)P reveals a helix-grip β-barrel fold; ORP3 binds PI(4)P but lacks sterol-binding due to a narrow hydrophobic tunnel; ORP3 and OSBP ORDs complement yeast OSH1-7 knockout lethality, but PI(4)P-binding site mutant of ORP3 does not, establishing PI(4)P transport as the essential conserved function. X-ray crystallography (2.6–2.7 Å), yeast OSH knockout complementation, PI4P-binding site mutagenesis PloS one High 33857182
1998 A Drosophila OSBP homolog (OSBP-Dm, 52% identity to mammalian OSBP) was identified and shown to rescue cell cycle arrest caused by Wee1 overexpression in fission yeast, establishing a functional connection between OSBP and cell cycle regulation. Yeast genetic suppressor screen, sequence homology analysis Biochimica et biophysica acta Low 9473651

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 A four-step cycle driven by PI(4)P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell 633 24209621
2005 Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature 351 16136145
2005 OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science (New York, N.Y.) 243 15746430
2017 Sterol transfer, PI4P consumption, and control of membrane lipid order by endogenous OSBP. The EMBO journal 188 28978670
2001 The OSBP-related protein family in humans. Journal of lipid research 158 11483621
2007 OSBP-related protein 8 (ORP8) suppresses ABCA1 expression and cholesterol efflux from macrophages. The Journal of biological chemistry 111 17991739
2003 The OSBP-related proteins: a novel protein family involved in vesicle transport, cellular lipid metabolism, and cell signalling. Biochimica et biophysica acta 101 12573443
2002 Oxysterol-binding-protein (OSBP)-related protein 4 binds 25-hydroxycholesterol and interacts with vimentin intermediate filaments. The Biochemical journal 95 11802775
2009 OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids. Journal of lipid research 87 19224871
2014 Oxysterol-binding protein (OSBP)-related protein 4 (ORP4) is essential for cell proliferation and survival. The Journal of biological chemistry 86 24742681
2015 OSBP-Related Protein Family: Mediators of Lipid Transport and Signaling at Membrane Contact Sites. International review of cell and molecular biology 84 26811291
2010 Sterol binding by OSBP-related protein 1L regulates late endosome motility and function. Cellular and molecular life sciences : CMLS 76 20690035
2005 Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. Experimental cell research 76 16143324
2014 OSBP-related protein 3 (ORP3) coupling with VAMP-associated protein A regulates R-Ras activity. Experimental cell research 73 25447204
1998 Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. The Biochemical journal 71 9806908
2015 OSBP-Related Protein Family in Lipid Transport Over Membrane Contact Sites. Lipid insights 68 26715851
2005 Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis. The Biochemical journal 64 15859942
2015 Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP. Antiviral research 57 25752737
1999 Chinese hamster ovary cells overexpressing the oxysterol binding protein (OSBP) display enhanced synthesis of sphingomyelin in response to 25-hydroxycholesterol. Journal of lipid research 55 9869656
2010 Multivesicular body formation requires OSBP-related proteins and cholesterol. PLoS genetics 52 20700434
2022 Coordination of inter-organelle communication and lipid fluxes by OSBP-related proteins. Progress in lipid research 51 34999137
2019 An Intrinsically Disordered Region in OSBP Acts as an Entropic Barrier to Control Protein Dynamics and Orientation at Membrane Contact Sites. Developmental cell 51 30905771
2011 OSBP-related protein 8 (ORP8) regulates plasma and liver tissue lipid levels and interacts with the nucleoporin Nup62. PloS one 51 21698267
2018 Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1. Journal of virology 50 29367253
2008 Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. The Journal of biological chemistry 50 18230613
2006 The OSBP-related proteins (ORPs): global sterol sensors for co-ordination of cellular lipid metabolism, membrane trafficking and signalling processes? Biochemical Society transactions 50 16709169
2003 Subfamily III of mammalian oxysterol-binding protein (OSBP) homologues: the expression and intracellular localization of ORP3, ORP6, and ORP7. Cell and tissue research 50 14593528
2007 Characterization of the sterol-binding domain of oxysterol-binding protein (OSBP)-related protein 4 reveals a novel role in vimentin organization. Experimental cell research 49 17350617
2017 Structure of Yeast OSBP-Related Protein Osh1 Reveals Key Determinants for Lipid Transport and Protein Targeting at the Nucleus-Vacuole Junction. Structure (London, England : 1993) 48 28319008
2017 Uncovering oxysterol-binding protein (OSBP) as a target of the anti-enteroviral compound TTP-8307. Antiviral research 46 28088354
2008 OSBP negatively regulates ABCA1 protein stability. The Journal of biological chemistry 45 18450749
2021 Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites. Nature communications 43 34103503
2010 OSBP- and FAN-mediated sterol requirement for spermatogenesis in Drosophila. Development (Cambridge, England) 43 20943709
2007 Expression of human OSBP-related protein 1L in macrophages enhances atherosclerotic lesion development in LDL receptor-deficient mice. Arteriosclerosis, thrombosis, and vascular biology 43 17478758
2007 The N terminus controls sterol binding while the C terminus regulates the scaffolding function of OSBP. The Journal of biological chemistry 41 18165705
2005 Inhibition of cholesterol biosynthesis by 25-hydroxycholesterol is independent of OSBP. Genes to cells : devoted to molecular & cellular mechanisms 41 16098143
2013 Oligo-astheno-teratozoospermia in mice lacking ORP4, a sterol-binding protein in the OSBP-related protein family. Genes to cells : devoted to molecular & cellular mechanisms 40 24245814
2010 OSBP-related protein 11 (ORP11) dimerizes with ORP9 and localizes at the Golgi-late endosome interface. Experimental cell research 39 20599956
1999 Family of human oxysterol binding protein (OSBP) homologues. A novel member implicated in brain sterol metabolism. Journal of lipid research 39 10588946
2019 Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds. Antiviral research 37 31271764
1998 A Drosophila homologue of oxysterol binding protein (OSBP)--implications for the role of OSBP. Biochimica et biophysica acta 36 9473651
2019 Salmonella Translocated Effectors Recruit OSBP1 to the Phagosome to Promote Vacuolar Membrane Integrity. Cell reports 31 31091452
2014 Characterization of the sterol and phosphatidylinositol 4-phosphate binding properties of Golgi-associated OSBP-related protein 9 (ORP9). PloS one 31 25255026
2008 Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein. Molecular neurodegeneration 31 18348724
2019 Transient Compound Treatment Induces a Multigenerational Reduction of Oxysterol-Binding Protein (OSBP) Levels and Prophylactic Antiviral Activity. ACS chemical biology 27 30576108
2018 Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP. Molecular biology of the cell 26 29540530
2015 MicroRNA124 Regulated Neurite Elongation by Targeting OSBP. Molecular neurobiology 26 26576957
2012 Silencing of OSBP-related protein 8 (ORP8) modifies the macrophage transcriptome, nucleoporin p62 distribution, and migration capacity. Experimental cell research 25 22683860
2018 OSBP-related protein-2 (ORP2): a novel Akt effector that controls cellular energy metabolism. Cellular and molecular life sciences : CMLS 24 29947926
2013 OSBP-related proteins: liganding by glycerophospholipids opens new insight into their function. Molecules (Basel, Switzerland) 24 24196413
2022 Ligand Recognition by the Lipid Transfer Domain of Human OSBP Is Important for Enterovirus Replication. ACS infectious diseases 22 35613096
2021 The emerging roles of OSBP-related proteins in cancer: Impacts through phosphoinositide metabolism and protein-protein interactions. Biochemical pharmacology 21 33556339
2018 Structure-activity relationship study of itraconazole, a broad-range inhibitor of picornavirus replication that targets oxysterol-binding protein (OSBP). Antiviral research 21 29807040
2018 Cadmium induced redistribution of cholesterol by upregulating ABCA1 and downregulating OSBP. Journal of inorganic biochemistry 21 30317066
2012 OSBP-related proteins (ORPs) in human adipose depots and cultured adipocytes: evidence for impacts on the adipocyte phenotype. PloS one 21 23028956
2011 Oxysterol-binding protein (OSBP) enhances replication of intracellular Salmonella and binds the Salmonella SPI-2 effector SseL via its N-terminus. Microbes and infection 21 21988961
2020 Activity and Resistance Assessment of a New OSBP Inhibitor, R034-1, in Phytophthora capsici and the Detection of Point Mutations in PcORP1 that Confer Resistance. Journal of agricultural and food chemistry 20 33191734
2017 Lipid-dependent regulation of exocytosis in S. cerevisiae by OSBP homolog (Osh) 4. Journal of cell science 20 28993464
2013 Oxysterol-binding protein (OSBP) is required for the perinuclear localization of intra-Golgi v-SNAREs. Molecular biology of the cell 20 24048449
2015 Sterol liganding of OSBP-related proteins (ORPs) regulates the subcellular distribution of ORP-VAPA complexes and their impacts on organelle structure. Steroids 19 25681634
2023 New insights into the OSBP‒VAP cycle. Current opinion in cell biology 18 37245352
2019 OSBP-related protein 2 (ORP2): Unraveling its functions in cellular lipid/carbohydrate metabolism, signaling and F-actin regulation. The Journal of steroid biochemistry and molecular biology 18 30716465
2011 OSBP-related protein 7 interacts with GATE-16 and negatively regulates GS28 protein stability. Experimental cell research 18 21669198
2021 Small Molecule Targeting of Oxysterol-Binding Protein (OSBP)-Related Protein 4 and OSBP Inhibits Ovarian Cancer Cell Proliferation in Monolayer and Spheroid Cell Models. ACS pharmacology & translational science 16 33860198
2018 OSBP-related protein 4L promotes phospholipase Cβ3 translocation from the nucleus to the plasma membrane in Jurkat T-cells. The Journal of biological chemistry 16 30237164
2014 OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle. Experimental cell research 16 24424245
2024 Orpinolide disrupts a leukemic dependency on cholesterol transport by inhibiting OSBP. Nature chemical biology 15 38907113
2005 Overexpression of OSBP-related protein 2 (ORP2) in CHO cells induces alterations of phospholipid species composition. Biochemistry and cell biology = Biochimie et biologie cellulaire 15 16234858
2024 Inhibition of OSBP blocks retrograde trafficking by inducing partial Golgi degradation. Nature chemical biology 14 38907112
2021 Structure of human ORP3 ORD reveals conservation of a key function and ligand specificity in OSBP-related proteins. PloS one 13 33857182
2007 Molecular characterization of a novel salt-inducible gene for an OSBP (oxysterol-binding protein)-homologue from soybean. Gene 12 17466467
2013 A vertebrate model for the study of lipid binding/transfer protein function: conservation of OSBP-related proteins between zebrafish and human. Biochemical and biophysical research communications 11 24326072
2003 OsBP-73, a rice gene, encodes a novel DNA-binding protein with a SAP-like domain and its genetic interference by double-stranded RNA inhibits rice growth. Plant molecular biology 10 12956528
2023 Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4. Journal of medicinal chemistry 9 36916802
2024 Minimalist Natural ORPphilin Macarangin B Delineates OSBP Biological Function. Journal of medicinal chemistry 8 39704626
2024 OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion. Cell reports 7 38536815
2023 Resistance Risk Assessment for the New OSBP Inhibitor Y18501 in Pseudoperonospora cubensis and Point Mutations (G705V, L798W, and I812F) in PscORP1 that Confer Resistance. Journal of agricultural and food chemistry 7 36898018
2015 TAT-OSBP-1-MKK6(E), a novel TAT-fusion protein with high selectivity for human ovarian cancer, exhibits anti-tumor activity. Medical oncology (Northwood, London, England) 7 25782870
2024 OSBP is a Major Determinant of Golgi Phosphatidylinositol 4-Phosphate Homeostasis. Contact (Thousand Oaks (Ventura County, Calif.)) 6 38405037
2022 Global effects of pharmacologic inhibition of OSBP in human umbilical vein endothelial cells. Steroids 5 35623602
2020 OSBP-Related Protein 5L Maintains Intracellular IP3/Ca2+ Signaling and Proliferation in T Cells by Facilitating PIP2 Hydrolysis. Journal of immunology (Baltimore, Md. : 1950) 5 31953353
2020 miR-195 Serves as a Tumor Suppressor in the Progression of Liposarcoma by Targeting OSBP. OncoTargets and therapy 5 32753887
2023 Activity of the new OSBP inhibitor Y18501 against Pseudoperonospora cubensis and its application for the control of cucumber downy mildew. Pesticide biochemistry and physiology 4 37532305
2025 Anti-SARS-CoV-2 Small Molecule Targeting of Oxysterol-Binding Protein (OSBP) Activates Cellular Antiviral Innate Immunity. ACS infectious diseases 3 40255103
2024 Oxysterol binding protein (OSBP) contributes to hepatitis E virus replication. Virology journal 2 39039546
2015 Delivery of Constitutively Active Mutant MKK6(E) With TAT-OSBP Induces Apoptosis in Human Ovarian Carcinoma HO8910 Cells. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2 26495757
2004 [Expression of OsBP-73 gene requires involvement of its intron in rice]. Zhi wu sheng li yu fen zi sheng wu xue xue bao = Journal of plant physiology and molecular biology 2 15583413
2025 Schweinfurthins and their analogues are highly selective cellular probes for oxysterol-binding protein (OSBP). RSC medicinal chemistry 1 41280340
2020 [A lipid exchange market : vectorial cholesterol transport by the protein OSBP]. Medecine sciences : M/S 1 32129748
2025 OSBP Participates in Neural Damage Repair by Regulating Lysosome Transport Under Oxidative Stress. Molecular neurobiology 0 39915357
2025 Repurposing oxiconazole to inhibit STING trafficking via OSBP and alleviate autoimmune pathology in Trex1-/- mice. International immunopharmacology 0 40319749
2025 Elaboration and profiling of the first OSBP degrader issued from natural Schweinfurthins. Bioorganic chemistry 0 40884917
2025 Docking and molecular dynamics simulations of ORPphilins targeting OSBP. Methods in enzymology 0 41765601
2024 OSBP is a major determinant of Golgi phosphatidylinositol 4-phosphate homeostasis. bioRxiv : the preprint server for biology 0 38187665
2007 [Preliminary screening of target genes of rice transcription factor OsBP-73]. Zhi wu sheng li yu fen zi sheng wu xue xue bao = Journal of plant physiology and molecular biology 0 17960050
2001 Fusion Expression and Purification of OSBP PH Domain and Preliminary Analysis of Its Second Structure. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 0 12035066