ABCA1
Encyclopedia
ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA), also known as the cholesterol efflux regulatory protein (CERP) is a protein
which in humans is encoded by the ABCA1 gene
. This transporter is a major regulator of cellular cholesterol
and phospholipid
homeostasis
.
and phospholipid
s to lipid-poor apolipoprotein
s (apo-A1 and apoE), which then form nascent high-density lipoproteins (HDL). It also mediates the transport of lipids between Golgi and cell membrane
. Since this protein is needed throughout the body it is expressed
ubiquitously as a 220-kDa
protein. It is present in higher quantities in tissues that shuttle or are involved in the turnover of lipids such as the liver, the small intestine and adipose tissue.
Factors that act upon the ABCA1 transporter's expression or its posttranslational modification
are also molecules that are involved in its subsequent function like fatty acid
s, cholesterol and also cytokine
s and cyclic adenosine monophosphate
.
and familial high-density lipoprotein deficiency. ABCA1 has been shown to be reduced in Tangier disease
which features physiological deficiencies of HDL.
with Apolipoprotein A1
, FADD
, XPC
and SNTB2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the ABCA1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. This transporter is a major regulator of cellular cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
.
Tangier's Disease
ABCA1 was discovered as the mutation causing Tangier's Disease by several groups in 1998. Gerd Schmitz's group in Germany and Michael Hayden's group in British Columbia were using standard genetics techniques and DNA from family pedigrees to locate the mutation. Richard Lawn's group at CV Therapeutics in Palo Alto, CA used cDNA microarrays, which were relatively new at the time, to assess gene expression profiles from cell lines created from normal and effected individuals. They showed cell lines from patients with Tangier's disease showed differential regulation of the ABCA1 gene. Subsequent sequencing of the gene identified the mutations. This group received an award from the American Heart Association for their discovery.Function
The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABCA, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABCA subfamily. Members of the ABCA subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. With cholesterol as its substrate, this protein functions as a cholesterol efflux pump in the cellular lipid removal pathway.Physiological role
ABCA1 mediates the efflux of cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s to lipid-poor apolipoprotein
Apolipoprotein
Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....
s (apo-A1 and apoE), which then form nascent high-density lipoproteins (HDL). It also mediates the transport of lipids between Golgi and cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. Since this protein is needed throughout the body it is expressed
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
ubiquitously as a 220-kDa
DA
DA, da, or dA may refer to:* Da , a Tony-winning play by Hugh Leonard* Da , a movie adaptation of the play by Hugh Leonard* Adi Da, a spiritual leader once known as Da Free John, and Da Love-Ananda...
protein. It is present in higher quantities in tissues that shuttle or are involved in the turnover of lipids such as the liver, the small intestine and adipose tissue.
Factors that act upon the ABCA1 transporter's expression or its posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
are also molecules that are involved in its subsequent function like fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s, cholesterol and also cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and cyclic adenosine monophosphate
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
.
Clinical significance
Mutations in this gene have been associated with Tangier diseaseTangier disease
Tangier disease is a rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein , often referred to as "good cholesterol," in the bloodstream.-Diagnosis:...
and familial high-density lipoprotein deficiency. ABCA1 has been shown to be reduced in Tangier disease
Tangier disease
Tangier disease is a rare inherited disorder characterized by a severe reduction in the amount of high density lipoprotein , often referred to as "good cholesterol," in the bloodstream.-Diagnosis:...
which features physiological deficiencies of HDL.
Interactions
ABCA1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Apolipoprotein A1
Apolipoprotein A1
Apolipoprotein A-I is a protein that in humans is encoded by the APOA1 gene. It has a specific role in lipid metabolism.Apolipoprotein A-I is the major protein component of high density lipoprotein in plasma. Chylomicrons secreted from the intestinal enterocyte also contain ApoA1 but it is quickly...
, FADD
FADD
Fas-Associated protein with Death Domain is an adaptor molecule that bridges the Fas-receptor, and other death receptors, to caspase-8 through its death domain to form the death-inducing signaling complex during apoptosis. -Signalling:...
, XPC
XPC (gene)
Xeroderma pigmentosum, complementation group C, also known as XPC, is a protein which in humans is encoded by the XPC gene. XPC is involved in the recognition of bulky DNA adducts in nucleotide excision repair.- Function :...
and SNTB2
SNTB2
Beta-2-syntrophin is a protein that in humans is encoded by the SNTB2 gene.-Further reading:...
.