Affinage

OSBP

Oxysterol-binding protein 1 · UniProt P22059

Length
807 aa
Mass
89.4 kDa
Annotated
2026-06-10
96 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OSBP is a sterol-binding lipid-transfer protein that operates at ER–Golgi membrane contact sites to set the cholesterol and PI(4)P gradients of the secretory pathway (PMID:24209621, PMID:28978670). It tethers the two organelles by binding Golgi PI(4)P through its PH domain and ER-resident VAP-A through its FFAT motif, while its OSBP-related domain (ORD) shuttles sterol anterograde and PI(4)P retrograde; hydrolysis of the transferred PI(4)P by the ER phosphatase Sac1 provides the thermodynamic drive for net cholesterol delivery against its gradient (PMID:24209621). The ORD encloses a single sterol molecule within a hydrophobic tunnel whose hydroxyl-coordinating residues and lid govern transport competence, a mechanism conserved from the yeast ortholog Osh4 to human OSBP (PMID:16136145, PMID:35613096), and an intrinsically disordered Gly-Pro-Ala-rich N-terminal segment acts as an entropic spacer that prevents homotypic membrane tethering and promotes diffusion and recycling at the contact site, with VAP-A flexibility and a T-shaped dimeric tethering geometry accommodating the moving ORDs (PMID:30905771, PMID:34103503). OSBP accounts for roughly half of cellular PI(4)P turnover and is a major, compartment-selective determinant of Golgi PI(4)P homeostasis (PMID:28978670, PMID:38405037). Cholesterol status controls OSBP phosphorylation and Golgi localization (PMID:9806908), and beyond lipid transfer OSBP serves as a cholesterol-regulated scaffold that assembles a ~440 kDa complex with the phosphatases HePTP and PP2A to dephosphorylate ERK1/2, an activity reversed by cholesterol depletion or oxysterols (PMID:15746430, PMID:18165705). Its lipid-transport function underlies diverse cellular processes: maintenance of intra-Golgi v-SNARE localization and COPI-dependent transport (PMID:24048449), destabilization of ABCA1 to limit cholesterol efflux (PMID:18450749), PI(4)P–cholesterol exchange at ER–insulin-granule contacts required for glucose-stimulated insulin secretion (PMID:38536815, PMID:29540530), and control of lysosomal PI(4)P to support anterograde lysosome transport in neurons (PMID:39915357). OSBP is exploited as an essential host factor by multiple positive-strand RNA viruses and by intracellular bacteria, being recruited to enterovirus and Aichi virus replication organelles and to the Salmonella-containing vacuole (PMID:25752737, PMID:29367253, PMID:31091452, PMID:21988961), and it is the direct target of antiviral, antileukemic, and trafficking-modulating small molecules including OSW-1, orpinolide, oxybipins, and oxiconazole (PMID:25752737, PMID:38907113, PMID:38907112, PMID:40319749).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 Medium

    Established that OSBP is a sterol-sensing protein whose phosphorylation and localization respond to cellular cholesterol, linking it to sphingomyelin synthesis at the Golgi.

    Evidence Subcellular fractionation, immunofluorescence, and sphingomyelin labeling in CHO cells under cholesterol depletion/repletion

    PMID:9806908 PMID:9869656

    Open questions at the time
    • Did not define the molecular lipid-transfer activity
    • Mechanism connecting Golgi localization to sphingomyelin synthesis unresolved
  2. 2005 High

    Defined the structural basis for sterol binding in the ORD and revealed an unanticipated scaffolding function coupling OSBP to ERK signaling.

    Evidence X-ray crystallography of the yeast Osh4 ORD with multiple sterol ligands; Co-IP, size-exclusion, and in vitro phosphatase assays of the OSBP–HePTP–PP2A complex

    PMID:15746430 PMID:16136145

    Open questions at the time
    • Structural work used yeast ortholog, not human OSBP
    • How sterol occupancy controls phosphatase complex assembly mechanistically undefined
  3. 2005 Medium

    Showed OSBP is dispensable for transcriptional suppression of cholesterol biosynthesis genes, separating its function from SREBP-pathway sterol sensing.

    Evidence siRNA knockdown with RT-PCR of sterol-regulated genes after 25-HC treatment

    PMID:16098143

    Open questions at the time
    • Negative result; does not exclude indirect roles in sterol homeostasis
  4. 2008 Medium

    Mapped the discrete sterol-binding region and demonstrated functional outputs of sterol binding, including ABCA1 destabilization and STAT3-dependent signaling.

    Evidence Domain truncation/point mutagenesis with sterol-binding and Co-IP mapping; RNAi and mutant-rescue ABCA1 half-life and efflux assays; phospho-site mutagenesis and ChIP for the 7-ketocholesterol/STAT3 pathway

    PMID:18165705 PMID:18230613 PMID:18450749

    Open questions at the time
    • Molecular mechanism of ABCA1 destabilization not resolved
    • Y394/STAT3 axis assessed in single lab and cell context
  5. 2013 High

    Resolved OSBP's core function as a counter-current ER-to-Golgi sterol/PI(4)P exchanger driven by Sac1-mediated PI(4)P hydrolysis, and connected this activity to Golgi v-SNARE organization.

    Evidence Reconstituted in vitro lipid transfer with liposomes, domain mutagenesis, and Sac1 epistasis; siRNA with domain-mutant rescue and ArfGAP1 epistasis for GS28/GS15 localization

    PMID:24048449 PMID:24209621

    Open questions at the time
    • In vitro cycle parameters versus in-cell kinetics
    • Link from lipid exchange to specific COPI/v-SNARE outcomes not fully mechanistic
  6. 2017 High

    Quantified OSBP's dominant contribution to cellular PI(4)P consumption and its role in setting the secretory-pathway lipid-order gradient.

    Evidence OSW-1 inhibition with live-cell PI(4)P/cholesterol reporters and lipidomics

    PMID:28978670

    Open questions at the time
    • Did not address compartment-specific selectivity in detail
  7. 2019 High

    Identified the disordered N-terminal region as an entropic regulator of tethering geometry, explaining how OSBP avoids homotypic bridging and recycles efficiently.

    Evidence In vitro reconstitution, FRAP, cryo-EM of contact sites, and hydrodynamic radius measurements with truncation mutants

    PMID:30905771

    Open questions at the time
    • In-cell relevance of entropic barrier under physiological crowding not directly measured
  8. 2021 High

    Visualized the architecture of a reconstituted OSBP–VAP-A contact site, showing flexible VAP-A and a T-shaped tethering dimer that permits ORD movement between membranes.

    Evidence Cryo-electron tomography and subtomogram averaging of reconstituted membrane contact sites

    PMID:34103503

    Open questions at the time
    • Static structural snapshots; transfer-cycle dynamics not captured
    • Native contact-site geometry in cells not resolved
  9. 2022 High

    Provided a human OSBP ORD–cholesterol structure and inhibitor-resistance mutants, linking sterol-tunnel residues to enterovirus replication dependency.

    Evidence X-ray crystallography of human OSBP ORD–cholesterol, site-directed mutagenesis, and viral replication assays with inhibitor resistance

    PMID:35613096

    Open questions at the time
    • Did not capture the dynamic transfer intermediate states
  10. 2024 High

    Extended OSBP's contact-site exchange function to specialized organelle contacts and confirmed it as a major, compartment-selective Golgi PI(4)P determinant and a druggable trafficking node.

    Evidence PI(4)P biosensors with genetic OSBP manipulation; live-cell imaging of ER–granule contacts with GSIS assays; thermal proteome profiling/CRISPR target ID for orpinolide; biophysical transport panel and retrograde/Shiga toxin assays for oxybipins

    PMID:38405037 PMID:38536815 PMID:38907112 PMID:38907113

    Open questions at the time
    • How OSBP is selectively recruited to distinct organelle contacts unresolved
    • In vivo physiological consequences of these specialized roles incomplete
  11. 2025 Medium

    Broadened OSBP's pathophysiological reach to neuronal lysosome transport, axonal repair, and innate-immune STING trafficking.

    Evidence Oxidative-stress neuronal model with OSBP manipulation, PI(4)P/PI(3)P and Arl8 binding assays, AAV in vivo TBI model; pharmacologic OSBP inhibition of STING trafficking in Trex1-/- mice

    PMID:39915357 PMID:40319749

    Open questions at the time
    • Direct lipid-transfer mechanism at lysosomes versus STING-bearing membranes not reconstituted
    • Single-lab in vivo findings

Open questions

Synthesis pass · forward-looking unresolved questions
  • How OSBP is selectively targeted and regulated at chemically and functionally distinct contact sites (Golgi, lysosome, secretory granule, pathogen vacuole, STING vesicle) — and how its phosphorylation state, scaffolding role, and lipid-transfer cycle are integrated in vivo — remains unresolved.
  • No unified model coupling recruitment determinants to transfer activity across organelles
  • Physiological loss-of-function phenotype in mammals not defined in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0140104 molecular carrier activity 3 GO:0060090 molecular adaptor activity 2 GO:0140299 molecular sensor activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005794 Golgi apparatus 4 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2 GO:0005764 lysosome 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-168256 Immune System 1
Partners
ABCA1ACBD3GS28PPP2CAPTPN7SACM1LVAPAVAPB
Complex memberships
ER-Golgi membrane contact site tether (OSBP-VAP-A)OSBP-HePTP-PP2A phosphatase complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 OSBP drives a four-step cycle at ER-Golgi membrane contact sites: (1) membrane tethering via PH domain (binding Golgi PI(4)P) and FFAT motif (binding ER VAP-A); (2) anterograde sterol transfer by the ORD domain from ER to Golgi; (3) retrograde PI(4)P transfer 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 against its concentration gradient. Reconstituted in vitro lipid transfer assay with liposomes, domain mutagenesis, fluorescence microscopy of tethering, epistasis with Sac1 Cell High 24209621
2005 The ORD (OSBP-related domain) of yeast Osh4 (OSBP ortholog) contains a hydrophobic tunnel that accommodates 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; open-lid structure reveals phospholipid-binding sites for membrane docking. X-ray crystallography at 1.5–2.5 Å resolution with ergosterol, cholesterol, and multiple hydroxycholesterol ligands; limited proteolysis; mutagenesis of basic residues Nature High 16136145
2005 OSBP forms an ~440 kDa cytosolic oligomeric complex with the tyrosine phosphatase HePTP (a PTPPBS family member), the serine/threonine phosphatase PP2A, and cholesterol; this complex has dual-specificity phosphatase activity toward phosphorylated ERK1/2 (pERK). Cholesterol depletion or oxysterol addition causes complex disassembly and elevation of pERK levels. Co-immunoprecipitation, size-exclusion chromatography, in vitro phosphatase assay, cholesterol depletion/supplementation experiments, OSBP overexpression rescue Science High 15746430
2007 The sterol-binding domain of OSBP maps to a central 51-amino-acid region (residues 408–459) that binds both cholesterol and 25-hydroxycholesterol; a Y458S mutation impairs sterol binding. The N-terminal glycine-alanine-rich region works with the PH domain to selectively gate cholesterol (but not 25-hydroxycholesterol) binding in the context of full-length OSBP. HePTP binds a C-terminal coiled-coil domain (residues 732–761); PP2A binds the C-terminal half independently of the coiled-coil. Domain truncation and point mutagenesis, cholesterol and 25-hydroxycholesterol binding assays, co-immunoprecipitation mapping The Journal of biological chemistry Medium 18165705
1998 Cholesterol status regulates OSBP phosphorylation and its subcellular distribution: in cholesterol-replete cells OSBP is in the cytoplasm/vesicles; upon cholesterol depletion OSBP is dephosphorylated and constitutively localizes to the Golgi apparatus. 25-hydroxycholesterol-stimulated sphingomyelin synthesis requires both adequate cellular cholesterol and OSBP phosphorylation. Subcellular fractionation, immunofluorescence microscopy, [3H]serine incorporation into sphingomyelin, cholesterol depletion/repletion in CHO and SRD6 cells The Biochemical journal Medium 9806908
1999 Overexpression of OSBP in CHO-K1 cells potentiates 25-hydroxycholesterol-stimulated sphingomyelin synthesis 2–3 fold; 25-hydroxycholesterol promotes translocation of OSBP to the Golgi apparatus where it stimulates conversion of ceramide to sphingomyelin; Golgi-enriched fractions from overexpressing cells show reduced diacylglycerol mass. [3H]serine and [3H]sphinganine incorporation assays, subcellular fractionation, immunofluorescence, in vitro enzyme activity assays Journal of lipid research Medium 9869656
2017 Endogenous OSBP is responsible for roughly half of total cellular PI(4)P consumption; blocking OSBP with OSW-1 causes sterol accumulation at ER/lipid droplets at the expense of the trans-Golgi network, reduces the lipid-order gradient along the secretory pathway, and uncouples PI4KIIIβ-driven PI(4)P production from OSBP-mediated consumption (generating traveling PI(4)P waves across the TGN). OSBP inhibition with OSW-1, live-cell PI(4)P and cholesterol reporters, lipidomics, fluorescence microscopy The EMBO journal High 28978670
2008 OSBP negatively regulates ABCA1 protein stability in a sterol-binding-domain-dependent manner: OSBP knockdown increases ABCA1 protein half-life ~3-fold and enhances cholesterol efflux without affecting ABCA1 mRNA or LXR transcriptional activity; mutations abrogating OSBP sterol binding prevent ABCA1 destabilization, while mutations disrupting Golgi or ER targeting do not. RNAi knockdown, protein half-life assay, co-transfection with domain mutants, cholesterol efflux assay, quantitative RT-PCR, LXR reporter assay The Journal of biological chemistry Medium 18450749
2008 7-ketocholesterol activates STAT3 in aortic endothelial cells via JAK2 and requires tyrosine-394 phosphorylation of OSBP1, leading to STAT3-dependent up-regulation of profilin-1 expression; the same pathway is activated in the aorta of diabetic rats. Luciferase reporter assay, phospho-specific antibodies, JAK2 inhibition, site-directed mutagenesis of OSBP1 Y394, chromatin immunoprecipitation, in vivo diabetic rat model The Journal of biological chemistry Medium 18230613
2013 OSBP is required for the perinuclear localization of intra-Golgi v-SNAREs GS28 and GS15; OSBP depletion by siRNA mislocalizes GS28/GS15 throughout the cytoplasm and reduces Golgi mannosidase II abundance. All three functional domains (ER-targeting FFAT, Golgi-targeting PH, sterol-binding ORD) are required. The OSBP-dependent GS28 mislocalization is rescued by co-depletion of ArfGAP1, implicating COPI vesicle budding as a downstream effector. siRNA knockdown, immunofluorescence, domain mutant rescue, genetic epistasis with ArfGAP1 double knockdown Molecular biology of the cell Medium 24048449
2019 A ~90 aa intrinsically disordered (Gly-Pro-Ala-rich) N-terminal sequence in OSBP acts as an entropic barrier: it prevents the two PH domains of the OSBP dimer from homotypically tethering two Golgi-like membranes, facilitates OSBP in-plane diffusion at membrane contact sites, and promotes its recycling. Its hydrodynamic radius is twice that of folded domains. In vitro reconstitution with liposomes, FRAP, cryo-electron microscopy of membrane contact sites, hydrodynamic radius measurements, truncation mutants Developmental cell High 30905771
2021 Cryo-tomography of a reconstituted in vitro membrane contact site reveals that VAP-A is a highly flexible ER transmembrane protein allowing variable intermembrane distances; the tethering region of the OSBP dimer adopts a central dimeric helical T-shaped structure, and this geometry facilitates movement of the two lipid-transfer ORD domains between the apposed membranes. Cryo-electron tomography and subtomogram averaging of in vitro reconstituted MCS with two lipid bilayers, VAP-A, and OSBP Nature communications High 34103503
2022 Crystal structure of the lipid transfer domain (ORD) of human OSBP in complex with endogenous cholesterol shows that cholesterol's hydrocarbon tail and tetracyclic ring occupy a hydrophobic tunnel while the hydroxyl group forms a hydrogen-bond network at the tunnel bottom. Systematic mutagenesis (M446W, L590W) identified residues that confer tolerance to the inhibitor T-00127-HEV2, and use of the M446W variant as a functional replacement revealed additional residues required for enterovirus replication. X-ray crystallography of human OSBP ORD–cholesterol complex, site-directed mutagenesis, viral replication assay with inhibitor resistance ACS infectious diseases High 35613096
2015 The natural compound OSW-1 (and structurally unrelated itraconazole) inhibit enterovirus replication by directly targeting OSBP; OSBP overexpression rescues viral replication in the presence of OSW-1, establishing OSBP as an essential host factor for enterovirus genome replication. OSBP overexpression rescue of antiviral inhibition, dose-response viral replication assays across multiple cell types and enterovirus strains Antiviral research High 25752737
2018 Aichi virus (a picornavirus) directly recruits the cholesterol transport machinery (OSBP, VAP-A/B, SAC1) to viral RNA replication organelles through protein–protein interactions between viral proteins (2B, 2BC, 2C, 3A, 3AB), ACBD3, OSBP, VAP, and SAC1; the OSBP–2B interaction enables PI(4)P-independent OSBP recruitment; cholesterol accumulates at replication organelles, and inhibition of OSBP-mediated cholesterol transfer impairs RNA replication. Co-immunoprecipitation, siRNA knockdown, immunofluorescence co-localization, electron microscopy, cholesterol staining, OSBP inhibitor treatment Journal of virology Medium 29367253
2019 Salmonella effector SseJ binds OSBP1 and, together with another SPI-2 effector SseL, recruits OSBP1 to the Salmonella-containing vacuole in a SPI-2 TTSS-dependent manner; knockdown of OSBP1 or deletion of VAPA/B (OSBP1-binding ER proteins) reduces vacuolar integrity and increases cytoplasmic bacterial release, demonstrating OSBP1 is required for vacuole membrane stability during intracellular Salmonella infection. Co-immunoprecipitation (SseJ–OSBP1 interaction), OSBP1 siRNA knockdown, VAPA/B deletion, fluorescence microscopy of vacuolar integrity, bacterial localization assay Cell reports Medium 31091452
2024 OSBP is the direct, phenotypically relevant target of the antileukemic compound orpinolide; orpinolide disrupts Golgi homeostasis via a mechanism requiring active PI(4)P signaling at the ER-Golgi membrane interface; thermal proteome profiling and genome-scale CRISPR-Cas9 screens confirmed OSBP as the direct target. Thermal proteome profiling, genome-scale CRISPR-Cas9 screens, multiomics profiling, Golgi morphology assays Nature chemical biology High 38907113
2024 OSBP inhibition by oxybipins blocks retrograde trafficking and causes partial Golgi degradation in lysosomes; a biophysical sterol transport protein assay panel confirmed oxybipins potently and selectively inhibit OSBP without affecting other sterol transporters; OSBP inhibition attenuates Shiga toxin toxicity by blocking retrograde transport. Sterol transport protein biophysical assay panel, retrograde trafficking assay, Shiga toxin cytotoxicity assay, proteomics of Golgi protein degradation, glycosylation analysis Nature chemical biology High 38907112
2024 OSBP is recruited to ER–insulin secretory granule contact sites in a Ca2+-dependent manner, regulated positively by PI4-kinases and negatively by the PI(4)P phosphatase Sac2; OSBP-mediated PI(4)P–cholesterol exchange at these contacts is required for glucose-stimulated insulin secretion; both acute pharmacologic inhibition and siRNA knockdown of OSBP suppress insulin secretion without affecting intracellular Ca2+ signaling. Live-cell imaging of OSBP at ER-granule contacts, siRNA knockdown, pharmacologic inhibition, glucose-stimulated insulin secretion assay, Ca2+ imaging Cell reports Medium 38536815
2024 Modulating OSBP levels at ER:Golgi membrane contact sites produces reciprocal changes in Golgi PI(4)P levels; OSBP has high capacity for PI(4)P turnover even at orthologous organelle membranes; endogenous OSBP does not significantly affect PI(4)P levels at the plasma membrane, establishing OSBP as a major, compartment-selective determinant of Golgi PI(4)P homeostasis. Acute and chronic genetic manipulation of OSBP expression, orthogonal organelle targeting, genetically-encoded PI(4)P biosensors Contact Medium 38405037
2025 OSBP participates in lysosome transport in neurons: oxidative stress reduces OSBP protein levels, leading to lysosomal PI(4)P accumulation that disrupts anterograde lysosome transport. OSBP overexpression restores PI(4)P/PI(3)P balance, improves Arl8 binding to lysosomes (shown by protein–liposome binding assay), increases lysosome localization in neurites, and promotes axonal injury repair in vivo. H2O2-induced oxidative stress model, OSBP overexpression and knockdown, PI(4)P/PI(3)P measurements, protein–liposome binding assay, live imaging of lysosome transport, AAV in vivo delivery in TBI mouse model Molecular neurobiology Medium 39915357
2010 In Drosophila, OSBP works together with the testis-specific VAP protein FAN (genetically and physically) to regulate sterol trafficking during spermatid individualization; OSBP-positive, sterol-enriched speckles appear at the leading edge of the individualization complex in wild-type but not in Osbp or fan mutants; male sterility of Osbp mutants is partially rescued by dietary sterol supplementation. Drosophila genetic mutant analysis, co-immunoprecipitation of OSBP–FAN interaction, immunofluorescence of sterol-enriched speckles, fertility rescue with dietary sterols Development Medium 20943709
2008 OSBP1 overexpression downregulates amyloidogenic processing of APP (reducing Aβ production), while OSBP1 knockdown has the opposite effect; OSBP1 causes accumulation of APP-Notch2 dimers in the Golgi, an effect reversed by 25-hydroxycholesterol treatment, linking OSBP1 sterol-sensing to APP trafficking. OSBP1 overexpression and RNAi knockdown, APP processing/Aβ quantification, immunofluorescence of APP-Notch2 localization, 25-hydroxycholesterol treatment Molecular neurodegeneration Medium 18348724
2018 OSBP knockdown in pancreatic β-cells reduces insulin granule stability (young granules are lost to lysosomal degradation) and suppresses glucose-stimulated insulin secretion; these effects were not rescued by exogenous cholesterol, distinguishing OSBP's proximal ER function from downstream ABC transporter-dependent cholesterol concentrating steps. Dual knockdown of OSBP and ABCG1 or ABCA1 supports their serial function in cholesterol supply for granule formation. RNAi knockdown, insulin granule tracking, glucose-stimulated insulin secretion assay, cholesterol supplementation rescue, dual knockdown epistasis Molecular biology of the cell Medium 29540530
2011 Salmonella infection causes redistribution of OSBP; the SPI-2 effector SseL binds the N-terminus of OSBP; OSBP is required for efficient intracellular replication of S. Typhimurium. Co-immunoprecipitation mapping of SseL–OSBP interaction, immunofluorescence of OSBP redistribution upon infection, OSBP knockdown and bacterial replication assay Microbes and infection Medium 21988961
2005 OSBP knockdown by siRNA (~90% reduction) does not affect 25-hydroxycholesterol-induced inhibition of HMG-CoA reductase or squalene epoxidase transcription, demonstrating that OSBP is not required for 25-HC-mediated suppression of cholesterol biosynthesis gene transcription. siRNA knockdown (~90% reduction), RT-PCR of sterol-regulated genes, 25-HC treatment Genes to cells Medium 16098143
2025 Oxiconazole inhibits STING trafficking via OSBP, suppressing cGAS-STING pathway-mediated type I IFN production; pharmacologic OSBP inhibition blocks STING trafficking and downstream inflammatory signaling in macrophages and fibroblasts and alleviates autoimmune pathology in Trex1-/- mice. Pharmacologic OSBP inhibition (oxiconazole), STING trafficking assay, IFN reporter assay, Trex1-/- mouse model, Listeria infection model International immunopharmacology Medium 40319749

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 638 24209621
2005 Structural mechanism for sterol sensing and transport by OSBP-related proteins. Nature 352 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 102 12573443
2002 Oxysterol-binding-protein (OSBP)-related protein 4 binds 25-hydroxycholesterol and interacts with vimentin intermediate filaments. The Biochemical journal 96 11802775
2009 OSBP-related protein 2 is a sterol receptor on lipid droplets that regulates the metabolism of neutral lipids. Journal of lipid research 89 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 85 26811291
2010 Sterol binding by OSBP-related protein 1L regulates late endosome motility and function. Cellular and molecular life sciences : CMLS 77 20690035
2005 Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. Experimental cell research 77 16143324
2014 OSBP-related protein 3 (ORP3) coupling with VAMP-associated protein A regulates R-Ras activity. Experimental cell research 74 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 65 15859942
2015 Broad-range inhibition of enterovirus replication by OSW-1, a natural compound targeting OSBP. Antiviral research 62 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
2022 Coordination of inter-organelle communication and lipid fluxes by OSBP-related proteins. Progress in lipid research 54 34999137
2011 OSBP-related protein 8 (ORP8) regulates plasma and liver tissue lipid levels and interacts with the nucleoporin Nup62. PloS one 53 21698267
2010 Multivesicular body formation requires OSBP-related proteins and cholesterol. PLoS genetics 52 20700434
2006 The OSBP-related proteins (ORPs): global sterol sensors for co-ordination of cellular lipid metabolism, membrane trafficking and signalling processes? Biochemical Society transactions 52 16709169
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
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 51 29367253
2008 Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. The Journal of biological chemistry 51 18230613
2003 Subfamily III of mammalian oxysterol-binding protein (OSBP) homologues: the expression and intracellular localization of ORP3, ORP6, and ORP7. Cell and tissue research 51 14593528
2017 Uncovering oxysterol-binding protein (OSBP) as a target of the anti-enteroviral compound TTP-8307. Antiviral research 49 28088354
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
2021 Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites. Nature communications 45 34103503
2008 OSBP negatively regulates ABCA1 protein stability. The Journal of biological chemistry 45 18450749
2010 OSBP- and FAN-mediated sterol requirement for spermatogenesis in Drosophila. Development (Cambridge, England) 44 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
2019 Differing activities of oxysterol-binding protein (OSBP) targeting anti-viral compounds. Antiviral research 39 31271764
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
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 32 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 30 30576108
2015 MicroRNA124 Regulated Neurite Elongation by Targeting OSBP. Molecular neurobiology 27 26576957
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
2013 OSBP-related proteins: liganding by glycerophospholipids opens new insight into their function. Molecules (Basel, Switzerland) 25 24196413
2012 Silencing of OSBP-related protein 8 (ORP8) modifies the macrophage transcriptome, nucleoporin p62 distribution, and migration capacity. Experimental cell research 25 22683860
2021 The emerging roles of OSBP-related proteins in cancer: Impacts through phosphoinositide metabolism and protein-protein interactions. Biochemical pharmacology 24 33556339
2018 OSBP-related protein-2 (ORP2): a novel Akt effector that controls cellular energy metabolism. Cellular and molecular life sciences : CMLS 24 29947926
2022 Ligand Recognition by the Lipid Transfer Domain of Human OSBP Is Important for Enterovirus Replication. ACS infectious diseases 23 35613096
2018 Cadmium induced redistribution of cholesterol by upregulating ABCA1 and downregulating OSBP. Journal of inorganic biochemistry 22 30317066
2018 Structure-activity relationship study of itraconazole, a broad-range inhibitor of picornavirus replication that targets oxysterol-binding protein (OSBP). Antiviral research 21 29807040
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
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 19 30716465
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
2011 OSBP-related protein 7 interacts with GATE-16 and negatively regulates GS28 protein stability. Experimental cell research 18 21669198
2024 Orpinolide disrupts a leukemic dependency on cholesterol transport by inhibiting OSBP. Nature chemical biology 17 38907113
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 17 33860198
2024 Inhibition of OSBP blocks retrograde trafficking by inducing partial Golgi degradation. Nature chemical biology 16 38907112
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
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
2021 Structure of human ORP3 ORD reveals conservation of a key function and ligand specificity in OSBP-related proteins. PloS one 13 33857182
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 12 24326072
2007 Molecular characterization of a novel salt-inducible gene for an OSBP (oxysterol-binding protein)-homologue from soybean. Gene 12 17466467
2023 Structure-Activity Relationships of Ligand Binding to Oxysterol-Binding Protein (OSBP) and OSBP-Related Protein 4. Journal of medicinal chemistry 10 36916802
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
2024 OSBP-mediated PI(4)P-cholesterol exchange at endoplasmic reticulum-secretory granule contact sites controls insulin secretion. Cell reports 8 38536815
2024 Minimalist Natural ORPphilin Macarangin B Delineates OSBP Biological Function. Journal of medicinal chemistry 8 39704626
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 8 36898018
2024 OSBP is a Major Determinant of Golgi Phosphatidylinositol 4-Phosphate Homeostasis. Contact (Thousand Oaks (Ventura County, Calif.)) 7 38405037
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
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 5 37532305
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
2025 Anti-SARS-CoV-2 Small Molecule Targeting of Oxysterol-Binding Protein (OSBP) Activates Cellular Antiviral Innate Immunity. ACS infectious diseases 4 40255103
2024 Oxysterol binding protein (OSBP) contributes to hepatitis E virus replication. Virology journal 3 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

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