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Gene Review

OSBP  -  oxysterol binding protein

Homo sapiens

Synonyms: OSBP1, Oxysterol-binding protein 1
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High impact information on OSBP

  • There have been recent advances in the study of lipid transfer proteins, such as ceramide transfer protein (CERT) and homologues of oxysterol binding protein (OSBP) [1].
  • Here, evidence that OSBP and ORPs are bona fide sterol carriers is discussed [2].
  • The crystal structure of a homolog of oxysterol binding protein solved by Jim Hurley and coworkers (Im et al., 2005) shows that this large family acts as cholesterol transporters, taking not only the lipid but also large numbers of water molecules into an internal pocket [3].
  • Identification of Kes1p as a negative effector for Golgi function provides the first direct insight into the biological role of any member of the OSBP family, and describes a novel pathway for the regulation of Golgi-derived transport vesicle biogenesis [4].
  • Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis [4].

Biological context of OSBP


Anatomical context of OSBP

  • In the yeast Saccharomyces cerevisiae an OSBP homologue is involved in membrane trafficking through the Golgi complex [6].
  • Thus, cholesterol functions through its interaction with OSBP outside of membranes to regulate the assembly of an oligomeric phosphatase that controls a key signaling pathway in the cell [9].
  • Novel members of the human oxysterol-binding protein family bind phospholipids and regulate vesicle transport [10].
  • In human tissues there was specific isoform distribution, with most tissues expressing varied levels of isoforms with the complete OSBP domain; while only whole brain, kidney, spleen, thymus, and thyroid expressed high levels of the isoforms associated with the truncated OSBP domain [11].
  • We previously demonstrated that this gene is highly expressed in CD34(+) hematopoietic progenitor cells, and deduced that the "full-length" ORP3 gene comprises 23 exons and encodes a predicted protein of 887 amino acids with a C-terminal OSBP domain and an N-terminal pleckstrin homology domain [11].

Associations of OSBP with chemical compounds

  • Together with OSBP, the identified gene products constitute a novel human protein family that may provide a link between organellar sterol status and membrane dynamics [6].
  • Our study implicates this new yeast gene family in ergosterol synthesis and provides comparative evidence of a role for human OSBP in cholesterol synthesis [12].
  • Cytosolic OSBP formed a approximately 440-kilodalton oligomer with a member of the PTPPBS family of tyrosine phosphatases, the serine/threonine phosphatase PP2A, and cholesterol [9].
  • Upon addition of 25-hydroxycholesterol, most of the OSBP became concentrated in large perinuclear structures that stained with lentil lectin, a protein that stains the Golgi apparatus [13].
  • The structures that contained OSBP were disrupted by brefeldin A, confirming their identification as Golgi [13].

Physical interactions of OSBP


Regulatory relationships of OSBP

  • OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation [9].
  • Analysis of a chimeric ORP3:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of ORP3 [18].
  • We found that decreasing OSBP expression by approximately 90% did not affect 25-HC-induced inhibition of transcription of 3-hydoxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and squalene epoxidase to any extent [19].

Other interactions of OSBP

  • We have investigated the structure, oxysterol-binding activity, cellular localization and function of ORP4 (also designated OSBP2 or HLM), a homologue that shares the highest degree of similarity with OSBP [16].
  • Here, OSBP was found to function as a cholesterol-binding scaffolding protein coordinating the activity of two phosphatases to control the extracellular signal-regulated kinase (ERK) signaling pathway [9].
  • ORP2 [OSBP (oxysterol-binding protein)-related protein 2] belongs to the 12-member mammalian ORP gene/protein family [20].
  • The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs [18].
  • The previously noted potential leucine zipper sequence in OSBP was not required for Golgi localization, nor was it essential for homodimer formation [13].

Analytical, diagnostic and therapeutic context of OSBP


  1. Inter-organelle membrane contact sites: through a glass, darkly. Levine, T., Loewen, C. Curr. Opin. Cell Biol. (2006) [Pubmed]
  2. Nonvesicular sterol transport: two protein families and a sterol sensor? Yang, H. Trends Cell Biol. (2006) [Pubmed]
  3. A new way for sterols to walk on water. Levine, T. Mol. Cell (2005) [Pubmed]
  4. Kes1p shares homology with human oxysterol binding protein and participates in a novel regulatory pathway for yeast Golgi-derived transport vesicle biogenesis. Fang, M., Kearns, B.G., Gedvilaite, A., Kagiwada, S., Kearns, M., Fung, M.K., Bankaitis, V.A. EMBO J. (1996) [Pubmed]
  5. Molecular and biochemical characterization of a novel oxysterol-binding protein (OSBP2) highly expressed in retina. Moreira, E.F., Jaworski, C., Li, A., Rodriguez, I.R. J. Biol. Chem. (2001) [Pubmed]
  6. Family of human oxysterol binding protein (OSBP) homologues. A novel member implicated in brain sterol metabolism. Laitinen, S., Olkkonen, V.M., Ehnholm, C., Ikonen, E. J. Lipid Res. (1999) [Pubmed]
  7. cDNA cloning of human oxysterol-binding protein and localization of the gene to human chromosome 11 and mouse chromosome 19. Levanon, D., Hsieh, C.L., Francke, U., Dawson, P.A., Ridgway, N.D., Brown, M.S., Goldstein, J.L. Genomics (1990) [Pubmed]
  8. A family of 12 human genes containing oxysterol-binding domains. Jaworski, C.J., Moreira, E., Li, A., Lee, R., Rodriguez, I.R. Genomics (2001) [Pubmed]
  9. OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Wang, P.Y., Weng, J., Anderson, R.G. Science (2005) [Pubmed]
  10. Novel members of the human oxysterol-binding protein family bind phospholipids and regulate vesicle transport. Xu, Y., Liu, Y., Ridgway, N.D., McMaster, C.R. J. Biol. Chem. (2001) [Pubmed]
  11. ORP3 splice variants and their expression in human tissues and hematopoietic cells. Collier, F.M., Gregorio-King, C.C., Apostolopoulos, J., Walder, K., Kirkland, M.A. DNA Cell Biol. (2003) [Pubmed]
  12. A new family of yeast genes implicated in ergosterol synthesis is related to the human oxysterol binding protein. Jiang, B., Brown, J.L., Sheraton, J., Fortin, N., Bussey, H. Yeast (1994) [Pubmed]
  13. Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. Ridgway, N.D., Dawson, P.A., Ho, Y.K., Brown, M.S., Goldstein, J.L. J. Cell Biol. (1992) [Pubmed]
  14. The OSBP-related protein family in humans. Lehto, M., Laitinen, S., Chinetti, G., Johansson, M., Ehnholm, C., Staels, B., Ikonen, E., Olkkonen, V.M. J. Lipid Res. (2001) [Pubmed]
  15. The oxysterol-binding protein homologue ORP1L interacts with Rab7 and alters functional properties of late endocytic compartments. Johansson, M., Lehto, M., Tanhuanpää, K., Cover, T.L., Olkkonen, V.M. Mol. Biol. Cell (2005) [Pubmed]
  16. Oxysterol-binding-protein (OSBP)-related protein 4 binds 25-hydroxycholesterol and interacts with vimentin intermediate filaments. Wang, C., JeBailey, L., Ridgway, N.D. Biochem. J. (2002) [Pubmed]
  17. Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum. Wyles, J.P., McMaster, C.R., Ridgway, N.D. J. Biol. Chem. (2002) [Pubmed]
  18. Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. Lehto, M., Hynynen, R., Karjalainen, K., Kuismanen, E., Hyvärinen, K., Olkkonen, V.M. Exp. Cell Res. (2005) [Pubmed]
  19. Inhibition of cholesterol biosynthesis by 25-hydroxycholesterol is independent of OSBP. Nishimura, T., Inoue, T., Shibata, N., Sekine, A., Takabe, W., Noguchi, N., Arai, H. Genes Cells (2005) [Pubmed]
  20. Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis. Hynynen, R., Laitinen, S., Käkelä, R., Tanhuanpää, K., Lusa, S., Ehnholm, C., Somerharju, P., Ikonen, E., Olkkonen, V.M. Biochem. J. (2005) [Pubmed]
  21. Golgi localization and phosphorylation of oxysterol binding protein in Niemann-Pick C and U18666A-treated cells. Mohammadi, A., Perry, R.J., Storey, M.K., Cook, H.W., Byers, D.M., Ridgway, N.D. J. Lipid Res. (2001) [Pubmed]
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