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Gene Review

SCARB2  -  scavenger receptor class B, member 2

Homo sapiens

Synonyms: 85 kDa lysosomal membrane sialoglycoprotein, AMRF, CD36 antigen-like 2, CD36L2, EPM4, ...
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Disease relevance of SCARB2


High impact information on SCARB2

  • LIMP-2/LGP85 also seems to have specific functions in maintaining endosomal transport and lysosomal biogenesis [5].
  • By analysis of hydrophobicity plots and by analogy to rat LIMPII, which has a 60% homology to CD36, a two-transmembrane domain model has been proposed [6].
  • The high density lipoprotein (HDL) receptor Scavenger Receptor BII (SR-BII) is encoded by an alternatively spliced mRNA from the SR-BI gene and is expressed in various tissues [7].
  • We have shown that SR-BII mediates HDL endocytosis through aclathrin-dependent, caveolae-independent pathway [7].
  • We conclude that SR-BII may influence cellular cholesterol trafficking and homeostasis in a manner that is distinct from SR-BI [8].

Biological context of SCARB2

  • The deduced amino acid sequence shows that hLGP85 consists of 478 amino acid residues (MW. 54,289) [9].
  • A full length cDNA for a human lysosomal membrane sialoglycoprotein (hLGP85) was isolated as a probe of the cDNA of rat LGP85 (rLGP85) from the cDNA library prepared from total mRNA of QGP-1NL cells, a human pancreatic islet tumor cell with a high metastatic activity [9].
  • We conclude that although human SR-BII is expressed by macrophages, contains cytoplasmic signalling motifs and localizes to caveolae, its ability to stimulate cholesterol efflux does not reflect enhanced hydrolysis of stored cholesteryl esters [10].
  • Whereas SR-BI was mainly ( approximately 70%) localized on the surface of transfected Chinese hamster ovary cells, as determined by biotinylation, HDL binding at 4 degrees C, and studies of enhanced green fluorescent protein-tagged SR-BI/II fusion proteins, the majority of SR-BII ( approximately 80-90%) was expressed intracellularly [8].
  • Moreover, mammalian class B scavenger receptors (SRs) conferred uptake of bacteria into nonphagocytic cells, with SR-BI and SR-BII uniquely mediating uptake of M. fortuitum, which suggests a conserved role for class B SRs in pattern recognition and innate immunity [11].

Anatomical context of SCARB2

  • Transcripts corresponding to SR-BI and SR-BII were detected in macrophages [12].
  • Thus, these findings provide important new insights into the role of LGP85 in the biogenesis and the maintenance of endosomes/lysosomes [13].
  • Despite being the abundant molecule of these compartments, whether LGP85 merely resides as one of the constituents of these membranes or plays a role in the regulation of endosome and lysosome biogenesis remains unclear [13].
  • Isolation and sequencing of a cDNA clone encoding the 85 kDa human lysosomal sialoglycoprotein (hLGP85) in human metastatic pancreas islet tumor cells [9].
  • Specific anti-peptide antisera identified SR-BII in human monocyte/macrophage THP-1 cells and, in recombinant cells, revealed receptor localization to caveolae, a plasma membrane microdomain that concentrates signal-transducer molecules and acts as a conduit for cholesterol flux between cells and lipoproteins [10].

Associations of SCARB2 with chemical compounds

  • We further demonstrate that overexpression of LGP85 impairs the endocytic membrane traffic out of these enlarged compartments, which may be correlated with or account for the accumulation of cholesterol observed in these compartments [13].
  • LGP85 (LIMP II) is a type III transmembrane glycoprotein that is located primarily in the limiting membranes of lysosomes and late endosomes [13].
  • Cytoplasmic tails of LIMPII and the invariant chain contain similar leucine-based sorting signals, but the invariant chain interacts only with AP1 and AP2, whereas LIMPII interacts strongly with AP3 [14].
  • Despite more rapid HDL uptake by SR-BII than SR-BI, selective cholesteryl ether uptake was significantly lower [8].
  • SR-BI and SR-BII levels were not correlated with serum testosterone levels [2].
  • These data support a role for LIMP-2 as the mannose-6-phosphate-independent trafficking receptor for beta-glucocerebrosidase [15].

Physical interactions of SCARB2

  • In solid phase binding assays, purified 125I-TSP1 bound to immobilized GST/LIMPII in a time-dependent and saturable manner [1].

Co-localisations of SCARB2

  • HDL protein that was internalized by SR-BII largely co-localized with transferrin in the endosomal recycling compartment [8].

Other interactions of SCARB2

  • 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 [16].
  • LIMPII.TSP1 complex formation was specifically blocked by soluble LIMPII fusion protein, by monospecific rabbit IgG directed against the LIMPII peptide and by CD36 fusion proteins containing the TSP1 binding domain [1].
  • To explore the existence of other related members, we have used the polymerase chain reaction with primers derived from highly conserved amino acid regions between CD36 and rat LIMPII [17].
  • In the active ROCK transfected cells the lysosomal proteins, cathepsin D, LIMPII, and LAMP1, were found throughout the cytoplasm in dispersed small vesicles, which were accessible to the endocytosed Texas Red-labeled transferrin [18].
  • Disruption of the lmpA gene encoding a protein (DdLIMP) belonging to the CD36/LIMPII family suppressed, to different degrees, most of the profilin-minus defects, including the increase in F-actin, but did not rescue the secretion defect [19].

Analytical, diagnostic and therapeutic context of SCARB2

  • In situ hybridization studies revealed that the S. domuncula CD36/LIMPII receptor is localized in the pinacocytes that surround the canals of the sponge [20].
  • Development of an isoform-specific Taqman Real Time PCR system and generation of isoform-specific polyclonal antibodies allowed us to measure SR-BI and SR-BII expression in various rabbit organs on mRNA and protein levels, respectively [21].
  • As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling motifs, we suggest that in brain SR-BII functions as a signal transducer receptor [22].
  • SR-BII was detected by Western blotting of immune precipitated crude cellular extracts [23].
  • SR-BI and SR-BII proteins were also detected by immunofluorescence staining of RPE cells in culture [23].


  1. Lysosomal integral membrane protein II binds thrombospondin-1. Structure-function homology with the cell adhesion molecule CD36 defines a conserved recognition motif. Crombie, R., Silverstein, R. J. Biol. Chem. (1998) [Pubmed]
  2. The predominance of one of the SR-BI isoforms is associated with increased esterified cholesterol levels not apoptosis in mink testis. Akpovi, C.D., Yoon, S.R., Vitale, M.L., Pelletier, R.M. J. Lipid Res. (2006) [Pubmed]
  3. Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors. Tserentsoodol, N., Gordiyenko, N.V., Pascual, I., Lee, J.W., Fliesler, S.J., Rodriguez, I.R. Mol. Vis. (2006) [Pubmed]
  4. LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice. Gamp, A.C., Tanaka, Y., Lüllmann-Rauch, R., Wittke, D., D'Hooge, R., De Deyn, P.P., Moser, T., Maier, H., Hartmann, D., Reiss, K., Illert, A.L., von Figura, K., Saftig, P. Hum. Mol. Genet. (2003) [Pubmed]
  5. At the acidic edge: emerging functions for lysosomal membrane proteins. Eskelinen, E.L., Tanaka, Y., Saftig, P. Trends Cell Biol. (2003) [Pubmed]
  6. A carboxyl terminal truncation mutant of CD36 is secreted and binds thrombospondin: evidence for a single transmembrane domain. Pearce, S.F., Wu, J., Silverstein, R.L. Blood (1994) [Pubmed]
  7. High density lipoprotein endocytosis by scavenger receptor SR-BII is clathrin-dependent and requires a carboxyl-terminal dileucine motif. Eckhardt, E.R., Cai, L., Shetty, S., Zhao, Z., Szanto, A., Webb, N.R., Van der Westhuyzen, D.R. J. Biol. Chem. (2006) [Pubmed]
  8. 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]
  9. Isolation and sequencing of a cDNA clone encoding the 85 kDa human lysosomal sialoglycoprotein (hLGP85) in human metastatic pancreas islet tumor cells. Fujita, H., Takata, Y., Kono, A., Tanaka, Y., Takahashi, T., Himeno, M., Kato, K. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  10. Human scavenger receptor class B type II (SR-BII) and cellular cholesterol efflux. Mulcahy, J.V., Riddell, D.R., Owen, J.S. Biochem. J. (2004) [Pubmed]
  11. Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection. Philips, J.A., Rubin, E.J., Perrimon, N. Science (2005) [Pubmed]
  12. 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]
  13. A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology. Kuronita, T., Eskelinen, E.L., Fujita, H., Saftig, P., Himeno, M., Tanaka, Y. J. Cell. Sci. (2002) [Pubmed]
  14. Structural requirements for interactions between leucine-sorting signals and clathrin-associated adaptor protein complex AP3. Rodionov, D.G., Höning, S., Silye, A., Kongsvik, T.L., von Figura, K., Bakke, O. J. Biol. Chem. (2002) [Pubmed]
  15. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Reczek, D., Schwake, M., Schröder, J., Hughes, H., Blanz, J., Jin, X., Brondyk, W., Van Patten, S., Edmunds, T., Saftig, P. Cell (2007) [Pubmed]
  16. 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]
  17. 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]
  18. Overexpression of ROCK in human breast cancer cells: evidence that ROCK activity mediates intracellular membrane traffic of lysosomes. Nishimura, Y., Itoh, K., Yoshioka, K., Tokuda, K., Himeno, M. Pathol. Oncol. Res. (2003) [Pubmed]
  19. Inactivation of lmpA, encoding a LIMPII-related endosomal protein, suppresses the internalization and endosomal trafficking defects in profilin-null mutants. Temesvari, L., Zhang, L., Fodera, B., Janssen, K.P., Schleicher, M., Cardelli, J.A. Mol. Biol. Cell (2000) [Pubmed]
  20. Matrix-mediated canal formation in primmorphs from the sponge Suberites domuncula involves the expression of a CD36 receptor-ligand system. Müller, W.E., Thakur, N.L., Ushijima, H., Thakur, A.N., Krasko, A., Le Pennec, G., Indap, M.M., Perovic-Ottstadt, S., Schröder, H.C., Lang, G., Bringmann, G. J. Cell. Sci. (2004) [Pubmed]
  21. Molecular characterization of rabbit scavenger receptor class B types I and II: portal to central vein gradient of expression in the liver. Ritsch, A., Tancevski, I., Schgoer, W., Pfeifhofer, C., Gander, R., Eller, P., Foeger, B., Stanzl, U., Patsch, J.R. J. Lipid Res. (2004) [Pubmed]
  22. Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction. Thilakawardhana, S., Everett, D.M., Murdock, P.R., Dingwall, C., Owen, J.S. Neurobiol. Aging (2005) [Pubmed]
  23. 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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