The protein encoded by this gene is an antagonist of angiopoietin 1 (ANGPT1) and endothelial TEK tyrosine kinase (TIE-2, TEK). The encoded protein disrupts the vascular remodeling ability of ANGPT1 and may induce endothelial cell apoptosis. Three transcript variants encoding three different isoforms have been found for this gene.
Angiotensinogen is a precursor of angiotensin II (Ang II),is expressed and synthesized largely in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. It has a key role in mediating vascular constriction and regulating salt and fluid homeostasis. The resulting product,angiotensin I,is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. Mutations in this gene are associated with susceptibility to essential hypertension,and can cause renal tubular dysgenesis,a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation,and inflammatory bowel disease.
Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Alternative splicing results in multiple transcript variants encoding distinct isoforms.
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