ATP-binding cassette, sub-family B member 11 (ABCB11), also known as the bile salt export pump (BSEP), 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 ...
which in humans is encoded by the
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 ...
.
Function
The product of the ''ABCB11'' gene is an ABC transporter named BSEP (bile salt export pump), or sPgp (sister of P-glycoprotein). This membrane-associated protein is a member of the superfamily of
ATP-binding cassette
The ABC transporters, ATP synthase (ATP)-binding cassette transporters are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to huma ...
(ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White).
This protein is a member of the MDR/TAP subfamily. Some members of the MDR/TAP subfamily are involved in
multidrug resistance
Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are ...
. This particular protein is responsible for the transport of
taurocholate and other cholate conjugates from
hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, bi ...
s (liver cells) to the
bile
Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
. In humans, the activity of this transporter is the major determinant of bile formation and bile flow.
Clinical significance
''ABCB11'' is a gene associated with
progressive familial intrahepatic cholestasis
Progressive familial intrahepatic cholestasis (PFIC) is a group of Genetic disorder, familial cholestasis, cholestatic conditions caused by defects in bile, biliary Epithelium, epithelial transporters. The clinical presentation usually occurs firs ...
type 2 (PFIC2).
PFIC2 caused by mutations in the ''ABCB11'' gene increases the risk of
hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
HCC most common ...
in early life.
Benign recurrent intrahepatic cholestasis
Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer.
A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...
(BRIC) is associated with episodic cholestatic jaundice and mutations in ''
ATP8B1
Probable phospholipid-transporting ATPase IC is an enzyme that in humans is encoded by the ''ATP8B1'' gene. This protein is associated with progressive familial intrahepatic cholestasis type 1 as well as benign recurrent intrahepatic cholestasis ...
'' or ''ABCB11''.
Bile salt
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
s from the
cytoplasm
The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
of
hepatocyte
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, bi ...
s are transported by the bile salt export pump (BSEP) into bile canaliculi. When bile salt export is deficient due to mutation in the ''ABCB11'' gene, this can lead to intrahepatic toxic accumulation of the bile salts. Individuals with such mutations have an increased incidence of
hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
HCC most common ...
or
cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...
.
References
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External links
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{{DEFAULTSORT:Abcb11