Angiopoietin-like 3, also known as ANGPTL3, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''ANGPTL3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
The protein encoded by this gene is a member of the
angiopoietin
Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from pree ...
-like family of secreted factors. It is expressed predominantly in the liver, and has the characteristic structure of angiopoietins, consisting of a
signal peptide
A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...
,
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
coiled-coil
A coiled coil is a structural motif in proteins in which 2–7
alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...
domain, and the
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
fibrinogen
Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...
(FBN)-like domain. The FBN-like domain in angiopoietin-like 3 protein was shown to bind
alpha-5/beta-3 integrins, and this binding induced endothelial
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
and
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
. This protein may also play a role in the regulation of
angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
.
Angptl3 also acts as dual inhibitor of
lipoprotein lipase
Lipoprotein lipase (LPL) (EC 3.1.1.34, systematic name triacylglycerol acylhydrolase (lipoprotein-dependent)) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-soluble ...
(LPL) and
endothelial lipase
Endothelial lipase (LIPG) is a form of lipase secreted by vascular endothelial cells in tissues with high metabolic rates and vascularization, such as the liver, lung, kidney, and thyroid gland. The LIPG enzyme is a vital component to many biologi ...
(EL),
thereby increasing plasma triglyceride, LDL cholesterol and HDL cholesterol in mice and humans.
ANGPTL3 inhibits endothelial lipase
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of HDL-phospholipid (PL), thereby increasing HDL-PL levels. Circulating PL-rich HDL particles have high cholesterol efflux abilities.
Angptl3 plays a major role in promoting uptake of circulating triglycerides into white adipose tissue in the fed state,
likely through activation by Angptl8, a feeding-induced hepatokine,
to inhibit postprandial LPL activity in cardiac and skeletal muscles,
as suggested by the ANGPTL3-4-8 model.
Clinical significance
In human, ANGPTL3 is a determinant factor of HDL level and positively correlates with plasma HDL cholesterol.
In humans with genetic loss-of-function variants in one copy of ''ANGPTL3'', the serum LDL-C levels are reduced. In those with loss-of-function variants in both copies of ''ANGPTL3'', low LDL-C, low HDL-C, and low triglycerides are seen ("
familial combined hypolipidemia").
References
Further reading
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External links
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* {{PDBe-KB2, Q9Y5C1, Angiopoietin-related protein 3