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Gene Review

SCARB1  -  scavenger receptor class B, member 1

Homo sapiens

Synonyms: CD36 and LIMPII analogous 1, CD36 antigen-like 1, CD36L1, CLA-1, CLA1, ...
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Disease relevance of SCARB1

  • Finally, E2 recognition by SR-BI was competed out in an isolate-specific manner both on the hepatoma cell line and on the human SR-BI-transfected cell line by an anti-HVR1 monoclonal antibody [1].
  • RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005) [2].
  • We tested for a significant contribution of common variant of these genes to coronary heart disease (CHD) risk and hypothesized that genetic-mediated PON activity and CLA-1/SR-BI receptor functional properties jointly reduce plasma oxidation status [3].
  • The scavenger receptor class B type I (SR-BI) has recently been shown to interact with hepatitis C virus (HCV) envelope glycoprotein E2, suggesting that it might be involved at some step of HCV entry into host cells [4].
  • With respect to efflux of cholesterol, the mRNA levels of NCEH and ABCA-1 were unchanged, whereas CLA-1 mRNA was slightly higher in atheroma [5].

High impact information on SCARB1

  • Studies of genetically manipulated strains of mice have established that SR-BI plays a key role in regulating lipoprotein metabolism and cholesterol transport to steroidogenic tissues and to the liver for biliary secretion [6].
  • The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues [6].
  • In addition, analysis of SR-BI-deficient mice has shown that SR-BI expression is important for alpha-tocopherol and nitric oxide metabolism, as well as normal red blood cell maturation and female fertility [6].
  • HDL also induces multiple cellular signals, which in endothelium occur through SR-BI and converge to activate eNOS [7].
  • HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner [8].

Chemical compound and disease context of SCARB1


Biological context of SCARB1

  • In contrast to known ligand-dependent apoptotic pathways, SR-BI-induced apoptosis is ligand-independent [14].
  • Further studies revealed that the sequenced cDNA clone may result by alternative splicing from a longer mRNA form having an insertion of 300 nucleotides located 126 nucleotides downstream from the initiation codon of cloned CLA-1 [15].
  • We found that liver-type fatty acid binding protein expression level is higher in SR-BI-overexpressing cells and that caveolin-1 and sterol response element binding protein-2 levels are reduced [9].
  • The SR-BI-apoE interactions may contribute to overall cholesterol homeostasis in cells and tissues that express SR-BI and apoE [16].
  • Thus our results demonstrate that EDL mediates both HDL binding and uptake, and the selective uptake of HDL-CE, independently of lipolysis and CLA-1 [17].

Anatomical context of SCARB1

  • We have identified the receptor responsible for E2 binding to human hepatic cells as the human scavenger receptor class B type I (SR-BI) [1].
  • When HDL levels are low, oxidative stress causes the relocation of eNOS away from caveolae, which turns on SR-BI-induced apoptosis and rapidly clears damaged cells to prevent further inflammatory damage to neighboring cells [14].
  • In both cultivated HepG2 hepatocytes and primary human monocyte-derived macrophages, testosterone led to a dose-dependent up-regulation of SR-BI, which was assessed on both the mRNA and the protein levels [18].
  • Furthermore, immunohistochemical analysis showed that immunoreactive mass of hSR-BI was detected in foam cells in human aortic atherosclerotic lesions and that there was no significant difference of staining patterns between the two Abs [19].
  • We propose that this direct interaction could modify SR-BI structure in cell membranes and potentiate CE uptake [20].

Associations of SCARB1 with chemical compounds

  • In Chinese hamster ovary cells, SAA promoted cellular cholesterol efflux in an SR-BI-dependent manner, whereas apoA-I did not [21].
  • To assess the effect of SAA on SR-BI-mediated efflux to high density lipoprotein (HDL), we compared normal HDL, acute phase HDL (AP-HDL, prepared from mice injected with lipopolysaccharide), and AdSAA-HDL (HDL prepared from mice overexpressing SAA) [21].
  • A mutant SR-BI (SR-BIdel509) that lacked only the leucine in the PDZ-interacting domain failed to interact with PDZK1 in vitro, while showing normal selective uptake function in nonpolarized cells [22].
  • In line with the ligand-binding specificity of CLA-1, phosphatidylcholine did not compete for selective HDL(3)-CE uptake [23].
  • Competition experiments demonstrated that CLA-1 ligands (oxidized HDL, oxidized and acetylated low-density lipoprotein and phosphatidylserine) inhibited selective HDL(3)-CE uptake [23].

Physical interactions of SCARB1

  • In an effort to elucidate the role of this interaction in vivo, the PDZK1-interacting domain of SR-BI was identified and mutated and expressed liver-specifically in mice [22].
  • SR-BI mediates cholesterol efflux via its interactions with lipid-bound ApoE. Structural mutations in SR-BI diminish cholesterol efflux [16].
  • We demonstrate that this functional HDL/SR-BI interaction only interferes with antibodies blocking HCV-E2 binding to CD81, a major HCV receptor, reflecting its prominent role during the cell entry process [24].
  • Thus, CD36 has been reported to bind oxidized LDL (OxLDL) and acetylated LDL (AcLDL), while SR-BI also binds native LDL and HDL [25].
  • The data confirmed that E2 through the ERs can positively regulate the HDL-R SR-BI through binding and activation of three ERE(1/2) motifs and identified SREBP-1a as a potential coactivator of the E2-ER-dependent effects on the HDL-R SR-BI gene [26].

Regulatory relationships of SCARB1

  • We conclude that SR-BII may influence cellular cholesterol trafficking and homeostasis in a manner that is distinct from SR-BI [27].
  • We conclude that HDL binding to SR-BI stimulates eNOS by increasing intracellular ceramide levels and is independent of an increase in intracellular calcium or Akt kinase phosphorylation [28].
  • Here we show that PDZK1 controls in a tissue-specific and post-transcriptional fashion the expression of SR-BI in vivo [29].
  • LPL stimulated [3H]cholesteryl oleyl ether uptake from labeled HDL3 by HEK 293 cells substantially, showing that LPL can induce selective CE uptake from HDL3 independent of SR-BI [30].

Other interactions of SCARB1

  • Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family [15].
  • Apolipoprotein E (apoE) and the lipoprotein receptor SR-BI play critical roles in lipid and lipoprotein metabolism [16].
  • These data, together with the phylogenetic analysis carried out for the members of this family, indicate that the LIMPII, CLA-1, and CD36 genes diverged early in evolution from an ancestor gene, possibly before the divergence between the arthropods and the vertebrates [31].
  • CONCLUSION: Two complementary cellular models providing SR-BI and ABCA1-dependent efflux should be used to measure the capacity of a biological fluid which contains a wide variety of components to promote cholesterol efflux [32].
  • Thus, in this hepatic cell model, SR-BI is associated with membrane rafts devoid of caveolin and its expression affects intracellular lipid binding and lipid sensor proteins [9].

Analytical, diagnostic and therapeutic context of SCARB1


  1. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. Scarselli, E., Ansuini, H., Cerino, R., Roccasecca, R.M., Acali, S., Filocamo, G., Traboni, C., Nicosia, A., Cortese, R., Vitelli, A. EMBO J. (2002) [Pubmed]
  2. Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques. Svensson, P.A., Englund, M.C., Snäckestrand, M.S., Hägg, D.A., Ohlsson, B.G., Stemme, V., Mattsson-Hulten, L., Thelle, D.S., Fagerberg, B., Wiklund, O., Carlsson, L.M., Carlsson, B. BMC cardiovascular disorders [electronic resource]. (2005) [Pubmed]
  3. Allelic variants of the human scavenger receptor class B type 1 and paraoxonase 1 on coronary heart disease: genotype-phenotype correlations. Rodríguez-Esparragón, F., Rodríguez-Pérez, J.C., Hernández-Trujillo, Y., Macías-Reyes, A., Medina, A., Caballero, A., Ferrario, C.M. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  4. High density lipoproteins facilitate hepatitis C virus entry through the scavenger receptor class B type I. Voisset, C., Callens, N., Blanchard, E., Op De Beeck, A., Dubuisson, J., Vu-Dac, N. J. Biol. Chem. (2005) [Pubmed]
  5. Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression. Forcheron, F., Legedz, L., Chinetti, G., Feugier, P., Letexier, D., Bricca, G., Beylot, M. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  6. The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. Rigotti, A., Miettinen, H.E., Krieger, M. Endocr. Rev. (2003) [Pubmed]
  7. Cholesterol binding, efflux, and a PDZ-interacting domain of scavenger receptor-BI mediate HDL-initiated signaling. Assanasen, C., Mineo, C., Seetharam, D., Yuhanna, I.S., Marcel, Y.L., Connelly, M.A., Williams, D.L., de la Llera-Moya, M., Shaul, P.W., Silver, D.L. J. Clin. Invest. (2005) [Pubmed]
  8. HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner. Gong, M., Wilson, M., Kelly, T., Su, W., Dressman, J., Kincer, J., Matveev, S.V., Guo, L., Guerin, T., Li, X.A., Zhu, W., Uittenbogaard, A., Smart, E.J. J. Clin. Invest. (2003) [Pubmed]
  9. Localization and regulation of SR-BI in membrane rafts of HepG2 cells. Rhainds, D., Bourgeois, P., Bourret, G., Huard, K., Falstrault, L., Brissette, L. J. Cell. Sci. (2004) [Pubmed]
  10. Normal and pathological human testes express hormone-sensitive lipase and the lipid receptors CLA-1/SR-BI and CD36. Arenas, M.I., Lobo, M.V., Caso, E., Huerta, L., Paniagua, R., Martín-Hidalgo, M.A. Hum. Pathol. (2004) [Pubmed]
  11. Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines. Khovidhunkit, W., Moser, A.H., Shigenaga, J.K., Grunfeld, C., Feingold, K.R. J. Lipid Res. (2001) [Pubmed]
  12. Comparison of expression and regulation of the high-density lipoprotein receptor SR-BI and the low-density lipoprotein receptor in human adrenocortical carcinoma NCI-H295 cells. Martin, G., Pilon, A., Albert, C., Vallé, M., Hum, D.W., Fruchart, J.C., Najib, J., Clavey, V., Staels, B. Eur. J. Biochem. (1999) [Pubmed]
  13. Probucol enhances the expression of human hepatic scavenger receptor class B type I, possibly through a species-specific mechanism. Hirano, K., Ikegami, C., Tsujii, K., Zhang, Z., Matsuura, F., Nakagawa-Toyama, Y., Koseki, M., Masuda, D., Maruyama, T., Shimomura, I., Ueda, Y., Yamashita, S. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  14. A novel ligand-independent apoptotic pathway induced by scavenger receptor class B, type I and suppressed by endothelial nitric-oxide synthase and high density lipoprotein. Li, X.A., Guo, L., Dressman, J.L., Asmis, R., Smart, E.J. J. Biol. Chem. (2005) [Pubmed]
  15. Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family. Calvo, D., Vega, M.A. J. Biol. Chem. (1993) [Pubmed]
  16. SR-BI mediates cholesterol efflux via its interactions with lipid-bound ApoE. Structural mutations in SR-BI diminish cholesterol efflux. Chroni, A., Nieland, T.J., Kypreos, K.E., Krieger, M., Zannis, V.I. Biochemistry (2005) [Pubmed]
  17. Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity. Strauss, J.G., Zimmermann, R., Hrzenjak, A., Zhou, Y., Kratky, D., Levak-Frank, S., Kostner, G.M., Zechner, R., Frank, S. Biochem. J. (2002) [Pubmed]
  18. Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux from macrophages. Langer, C., Gansz, B., Goepfert, C., Engel, T., Uehara, Y., von Dehn, G., Jansen, H., Assmann, G., von Eckardstein, A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  19. Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions. Hirano, K., Yamashita, S., Nakagawa, Y., Ohya, T., Matsuura, F., Tsukamoto, K., Okamoto, Y., Matsuyama, A., Matsumoto, K., Miyagawa, J., Matsuzawa, Y. Circ. Res. (1999) [Pubmed]
  20. Lipid free apolipoprotein E binds to the class B Type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from lipoproteins. Bultel-Brienne, S., Lestavel, S., Pilon, A., Laffont, I., Tailleux, A., Fruchart, J.C., Siest, G., Clavey, V. J. Biol. Chem. (2002) [Pubmed]
  21. Serum amyloid A promotes cholesterol efflux mediated by scavenger receptor B-I. van der Westhuyzen, D.R., Cai, L., de Beer, M.C., de Beer, F.C. J. Biol. Chem. (2005) [Pubmed]
  22. A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver. Silver, D.L. J. Biol. Chem. (2002) [Pubmed]
  23. The human breast carcinoma cell line HBL-100 acquires exogenous cholesterol from high-density lipoprotein via CLA-1 (CD-36 and LIMPII analogous 1)-mediated selective cholesteryl ester uptake. Pussinen, P.J., Karten, B., Wintersperger, A., Reicher, H., McLean, M., Malle, E., Sattler, W. Biochem. J. (2000) [Pubmed]
  24. High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. Dreux, M., Pietschmann, T., Granier, C., Voisset, C., Ricard-Blum, S., Mangeot, P.E., Keck, Z., Foung, S., Vu-Dac, N., Dubuisson, J., Bartenschlager, R., Lavillette, D., Cosset, F.L. J. Biol. Chem. (2006) [Pubmed]
  25. CLA-1 is an 85-kD plasma membrane glycoprotein that acts as a high-affinity receptor for both native (HDL, LDL, and VLDL) and modified (OxLDL and AcLDL) lipoproteins. Calvo, D., Gómez-Coronado, D., Lasunción, M.A., Vega, M.A. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  26. Estrogen activates the high-density lipoprotein receptor gene via binding to estrogen response elements and interaction with sterol regulatory element binding protein-1A. Lopez, D., Sanchez, M.D., Shea-Eaton, W., McLean, M.P. Endocrinology (2002) [Pubmed]
  27. High density lipoprotein uptake by scavenger receptor SR-BII. Eckhardt, E.R., Cai, L., Sun, B., Webb, N.R., van der Westhuyzen, D.R. J. Biol. Chem. (2004) [Pubmed]
  28. High density lipoprotein binding to scavenger receptor, Class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner. Li, X.A., Titlow, W.B., Jackson, B.A., Giltiay, N., Nikolova-Karakashian, M., Uittenbogaard, A., Smart, E.J. J. Biol. Chem. (2002) [Pubmed]
  29. Targeted disruption of the PDZK1 gene in mice causes tissue-specific depletion of the high density lipoprotein receptor scavenger receptor class B type I and altered lipoprotein metabolism. Kocher, O., Yesilaltay, A., Cirovic, C., Pal, R., Rigotti, A., Krieger, M. J. Biol. Chem. (2003) [Pubmed]
  30. Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI. Rinninger, F., Brundert, M., Brosch, I., Donarski, N., Budzinski, R.M., Greten, H. J. Lipid Res. (2001) [Pubmed]
  31. The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) gene family: cellular distribution, chromosomal location, and genetic evolution. Calvo, D., Dopazo, J., Vega, M.A. Genomics (1995) [Pubmed]
  32. Comparison of different cellular models measuring in vitro the whole human serum cholesterol efflux capacity. Mweva, S., Paul, J.L., Cambillau, M., Goudouneche, D., Beaune, P., Simon, A., Fournier, N. Eur. J. Clin. Invest. (2006) [Pubmed]
  33. Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake. Cai, L., de Beer, M.C., de Beer, F.C., van der Westhuyzen, D.R. J. Biol. Chem. (2005) [Pubmed]
  34. Human retinal pigment epithelial cells express scavenger receptors BI and BII. Duncan, K.G., Bailey, K.R., Kane, J.P., Schwartz, D.M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
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