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Function

Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.

Angiotensin-2

Acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone (PubMed:10619573, PubMed:17138938). Acts by binding to angiotensin receptors AGTR1 and AGTR2 (PubMed:1567413). Also binds the DEAR/FBXW7-AS1 receptor (By similarity).

Angiotensin-3

Stimulates aldosterone release.

Angiotensin 1-7

Is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects. Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).

Involvement in disease

Essential hypertension

EHT

A condition in which blood pressure is consistently higher than normal with no identifiable cause.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Renal tubular dysgenesis

RTD

Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Beta-decarboxylation of Asp-25 in angiotensin-2, by mononuclear leukocytes produces alanine (PubMed:17138938). The resulting peptide form, angiotensin-A, has the same affinity for the AT1 receptor as angiotensin-2, but a higher affinity for the AT2 receptor (PubMed:17138938).

In response to low blood pressure, the enzyme renin/REN cleaves angiotensinogen to produce angiotensin-1 (PubMed:12045255). Angiotensin-1 is a substrate of ACE (angiotensin converting enzyme) that removes a dipeptide to yield the physiologically active peptide angiotensin-2 (PubMed:10969042, PubMed:4322742). Angiotensin-1 and angiotensin-2 can be further processed to generate angiotensin-3, angiotensin-4 (PubMed:10969042, PubMed:11815627). Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4 (PubMed:10969042, PubMed:11815627). Angiotensin 1-7 has also been proposed to be cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME (neprilysin) (PubMed:15283675).

The disulfide bond is labile. Angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized disulfide-bonded form, which preferentially interacts with receptor-bound renin.

Sequence similarities

Belongs to the serpin family.

Tissue specificity

Expressed by the liver and secreted in plasma.

Cellular localization

  • Secreted

Alternative names

SERPINA8, AGT, Angiotensinogen, Serpin A8

Target type

Proteins

Primary research area

Cardiovascular

Molecular weight

53154Da

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