SCARB1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene.[1] SR-BI functions as a receptor for high-density lipoprotein.[2]

Function

Scavenger receptor class B, type I (SR-BI) is an integral membrane protein found in numerous cell types/tissues, including the liver and adrenal. 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.[3] 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 lipid soluble vitamin uptake.[4]

In melanocytic cells SCARB1 gene expression may be regulated by the MITF.[5]

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 SB-RI during egg development, indicating that cholesterol efflux may be at peak levels during developmental stages.[6]

Clinical significance

SCARB1 along with CD81 is the receptor for the entry of the Hepatitis C virus into liver cells.[7]

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.[8][9]

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.[10]

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. "Entrez Gene: SCARB1 Scavenger receptor class B, member 1".
  2. 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. doi:10.1126/science.271.5248.518. PMID 8560269.
  3. 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.
  4. 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: E1–7. doi:10.1111/j.1749-6632.2011.06205.x. PMID 22239457.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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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