Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''SCARB1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. SR-BI functions as a receptor for

high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

Function

Scavenger receptor class B, type I (SR-BI) is an

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...

found in numerous cell types/tissues, including

enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase ...

s, the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

and

adrenal The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...

gland. It is best known for its role in facilitating the uptake of

cholesteryl ester 300px, Cholesteryl oleate, a member of the cholesteryl ester family Cholesteryl esters are a type of dietary lipid and are ester derivatives of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl g ...

s from

s in the liver. This process drives the movement of

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

from peripheral tissues towards the

, where cholesterol can either be secreted via the bile duct or be used to synthesise steroid hormones. This movement of

is known as

reverse cholesterol transport Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine. Enhancing reverse cholesterol transport is considered a po ...

and is a protective mechanism against the development of

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

, which is the principal cause of

heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...

and

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

. SR-BI is crucial in

carotenoid Carotenoids () are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, archaea, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, corn, tomatoes, cana ...

and

vitamin E Vitamin E is a group of eight compounds related in molecular structure that includes four tocopherols and four tocotrienols. The tocopherols function as fat-soluble antioxidants which may help protect cell membranes from reactive oxygen speci ...

uptake in the small intestine. SR-B1 is upregulated in times of vitamin A deficiency and downregulated if vitamin A status is in the normal range. In melanocytic cells SCARB1 gene expression may be regulated by the

MITF Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...

Species distribution

SR-BI has also been identified in the livers of non-mammalian species (

turtle Turtles are reptiles of the order (biology), order Testudines, characterized by a special turtle shell, shell developed mainly from their ribs. Modern turtles are divided into two major groups, the Pleurodira (side necked turtles) and Crypt ...

goldfish The goldfish (''Carassius auratus'') is a freshwater fish in the family Cyprinidae of the order Cypriniformes. It is commonly kept as a pet in indoor aquariums, and is one of the most popular aquarium fish. Goldfish released into the w ...

shark Sharks are a group of elasmobranch cartilaginous fish characterized by a ribless endoskeleton, dermal denticles, five to seven gill slits on each side, and pectoral fins that are not fused to the head. Modern sharks are classified within the ...

chicken The chicken (''Gallus gallus domesticus'') is a domesticated subspecies of the red junglefowl (''Gallus gallus''), originally native to Southeast Asia. It was first domesticated around 8,000 years ago and is now one of the most common and w ...

frog A frog is any member of a diverse and largely semiaquatic group of short-bodied, tailless amphibian vertebrates composing the order (biology), order Anura (coming from the Ancient Greek , literally 'without tail'). Frog species with rough ski ...

, 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.

Clinical significance

SCARB1 along with

CD81 CD81 molecule, also known as CD81 (Cluster of Differentiation 81), is a protein which in humans is encoded by the ''CD81'' gene. It is also known as 26 kDa cell surface protein, TAPA-1 (Target of the Antiproliferative Antibody 1), and Tetraspanin- ...

is the receptor for the entry of the

Hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepatoc ...

into liver cells.

Preclinical research

Although malignant tumors are known to display extreme

heterogeneity Homogeneity and heterogeneity are concepts relating to the uniformity of a substance, process or image. A homogeneous feature is uniform in composition or character (i.e., color, shape, size, weight, height, distribution, texture, language, i ...

, overexpression of SR-B1 is a relatively consistent marker in cancerous tissues. While SR-B1 normally mediates the transfer of cholesterol between

s (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. SR-B1 mediated delivery has also been used in the transfection of cancer cells with

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20–24 base pairs in length, similar to microRNA (miRNA), and operating within the RN ...

, or small interfering RNAs. This therapy causes

RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...

, in which short segments of double stranded RNA acts to silence targeted

oncogenes An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

post-transcription. SR-B1 mediation reduces siRNA degradation and off-target accumulation while enhancing delivery to targeted tissues. In "metastatic and

taxane Taxanes are a class of diterpenes. They were originally identified from plants of the genus ''Taxus'' (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA app ...

-resistant models of ovarian cancer, rHDL-mediated siren delivery improved responses.

Function

Species distribution

Clinical significance

Preclinical research

Interactive pathway map

References

Further reading