SCARB1

Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene.[5] SR-BI functions as a receptor for high-density lipoprotein.[6]

SCARB1
Identifiers
AliasesSCARB1, CD36L1, CLA-1, CLA1, HDLQTL6, SR-BI, SRB1, scavenger receptor class B member 1
External IDsOMIM: 601040 MGI: 893578 HomoloGene: 21132 GeneCards: SCARB1
Orthologs
SpeciesHumanMouse
Entrez

949

20778

Ensembl

ENSG00000073060

ENSMUSG00000037936

UniProt

Q8WTV0

Q61009

RefSeq (mRNA)

NM_005505
NM_001082959

NM_001205082
NM_001205083
NM_016741

RefSeq (protein)

NP_001192011
NP_001192012
NP_058021

Location (UCSC)Chr 12: 124.78 – 124.88 MbChr 5: 125.35 – 125.42 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

Scavenger receptor class B, type I (SR-BI) is an integral membrane protein found in numerous cell types/tissues, including enterocytes, the liver and adrenal gland. It is best known for its role in facilitating the uptake of cholesteryl esters from high-density lipoproteins in the liver. This process drives the movement of cholesterol from peripheral tissues towards the liver, where cholesterol can either be secreted via the bile duct or be used to synthesise steroid hormones.[7] This movement of cholesterol is known as reverse cholesterol transport and is a protective mechanism against the development of atherosclerosis, which is the principal cause of heart disease and stroke.

SR-BI is crucial in carotenoid and vitamin E uptake in the small intestine.[8][9] SR-B1 is upregulated in times of vitamin A deficiency and downregulated if vitamin A status is in the normal range.[10]

In melanocytic cells SCARB1 gene expression may be regulated by the MITF.[11]

Species distribution

SR-BI has also been identified in the livers of non-mammalian species (turtle, goldfish, shark, chicken, frog, and skate), suggesting it emerged early in vertebrate evolutionary history. The turtle also seems to upregulate SR-BI during egg development, indicating that cholesterol efflux may be at peak levels during developmental stages.[12]

Clinical significance

SCARB1 along with CD81 is the receptor for the entry of the Hepatitis C virus into liver cells.[13]

Preclinical research

Although malignant tumors are known to display extreme heterogeneity, overexpression of SR-B1 is a relatively consistent marker in cancerous tissues. While SR-B1 normally mediates the transfer of cholesterol between high-density lipoproteins (HDL) and healthy cells, it also facilitates the selective uptake of cholesterol by malignant cells. In this way, upregulation of the SR-B1 receptor becomes an enabling factor for self-sufficient proliferation in cancerous tissue.[14][15]

SR-B1 mediated delivery has also been used in the transfection of cancer cells with siRNA, or small interfering RNAs. This therapy causes RNA interference, in which short segments of double stranded RNA acts to silence targeted oncogenes post-transcription. SR-B1 mediation reduces siRNA degradation and off-target accumulation while enhancing delivery to targeted tissues. In "metastatic and taxane-resistant models of ovarian cancer, rHDL-mediated siren delivery improved responses.[16]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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Statin Pathway edit
  1. The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

References

  1. GRCh38: Ensembl release 89: ENSG00000073060 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000037936 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: SCARB1 Scavenger receptor class B, member 1".
  6. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M (January 1996). "Identification of scavenger receptor SR-BI as a high density lipoprotein receptor". Science. 271 (5248): 518–20. Bibcode:1996Sci...271..518A. doi:10.1126/science.271.5248.518. PMID 8560269. S2CID 249922.
  7. Rhainds D, Brissette L (January 2004). "The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders". The International Journal of Biochemistry & Cell Biology. 36 (1): 39–77. doi:10.1016/s1357-2725(03)00173-0. PMID 14592533.
  8. Valacchi G, Sticozzi C, Lim Y, Pecorelli A (July 2011). "Scavenger receptor class B type I: a multifunctional receptor". Annals of the New York Academy of Sciences. 1229 (1): E1-7. Bibcode:2011NYASA1229E...1V. doi:10.1111/j.1749-6632.2011.06205.x. PMID 22239457. S2CID 7844031.
  9. van Bennekum A, Werder M, Thuahnai ST, Han CH, Duong P, Williams DL, et al. (March 2005). "Class B scavenger receptor-mediated intestinal absorption of dietary beta-carotene and cholesterol". Biochemistry. 44 (11): 4517–25. doi:10.1021/bi0484320. PMID 15766282.
  10. Blaner WS (2020). "Vitamin A". In BP Marriott, DF Birt, VA Stallings, AA Yates (eds.). Present Knowledge in Nutrition, Eleventh Edition. London, United Kingdom: Academic Press (Elsevier). pp. 73–92. ISBN 978-0-323-66162-1.
  11. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
  12. Duggan AE, Marie RS, Callard IP (April 2002). "Expression of SR-BI (Scavenger Receptor Class B Type I) in turtle (Chrysemys picta) tissues and other nonmammalian vertebrates". The Journal of Experimental Zoology. 292 (5): 430–4. doi:10.1002/jez.10067. PMID 11857477.
  13. Kapadia SB, Barth H, Baumert T, McKeating JA, Chisari FV (January 2007). "Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I" (PDF). Journal of Virology. 81 (1): 374–83. doi:10.1128/JVI.01134-06. PMC 1797271. PMID 17050612.
  14. Mooberry LK, Sabnis NA, Panchoo M, Nagarajan B, Lacko AG (December 2016). "Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging". Frontiers in Pharmacology. 7 (466): 466. doi:10.3389/fphar.2016.00466. PMC 5156841. PMID 28018216.
  15. Gutierrez-Pajares JL, Ben Hassen C, Chevalier S, Frank PG (2016). "SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer". Frontiers in Pharmacology. 7: 338. doi:10.3389/fphar.2016.00338. PMC 5054001. PMID 27774064.
  16. Rajora MA, Zheng G (2016). "Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy". Frontiers in Pharmacology. 7 (Art. 326): 326. doi:10.3389/fphar.2016.00326. PMC 5037127. PMID 27729859.

Further reading

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