Candidate Genes Diabetic Retinopathy

Angiotensinogen (serpin peptidase inhibitor, clade A, member 8)

Official Symbol
AGT
Alternative Names
serpin A8
angiotensin I
angiotensin II
pre-angiotensinogen
alpha-1 antiproteinase, antitrypsin
serine (or cysteine) proteinase inhibitor
Description
The angiotensin family of peptides is important in the regulation of blood volume, vascular resistance and electrolyte balance. Angiotensin II, the main peptide of the renin-angiotensin system, produces a variety of physiological effects. It is produced in a cascade whereby the precursor peptide angiotensinogen is cleaved to produce renin and angiotensin I. Angiotensin-converting enzyme then acts on angiotensin I to yield the octapeptide angiotensin II, and further processing generates angiotensins III and IV . These peptides act on three angiotensin receptor subtypes, AT1, AT2 and AT4, the properties of which are summarized below. The actions of angiotensin II are primarily mediated by AT1, whereas AT2 preferentially binds angiotensin III and AT4 is selective for angiotensin IV. 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.
Location
1q42.2
Map
Chr 17
Start: 230,838,269 bp from pter
End: 230,850,336 bp from pter
Size: 12,068 bases
Orientation: minus strand
Exons and Introns
5 exons and 15 distinct introns (13 gt-ag, 1 gc-ag, 1 other)
Location
1391 bp
Nucleotide Sequence
Aminoacid Sequence
Variation
rs699 C/T
Motif
Pfam: Serpin
PROSITE: SERPIN
Pathway
Renin-angiotensin system
Interactors
Protein interactors
Prolylcarboxypeptidase
Aspartyl aminopeptidase
Proteoglycan 2
Prolyl endopeptidase
Meprin A alpha
Anigotensin 1 converting enzyme 2
Kininogen
Chymase 1
Post Translational Modification
Beta-decarboxylation of Asp-34 in angiotensin-2, by mononuclear leukocytes produces alanine. 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.

Disulfide bond
Glycosylation
Proteolytic Cleavage
Molecular Weight
53154 da
Molecular Class
Peptide hormone
Molecular Function
Vasoconstrictor
Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis. Angiotensin-1 is a substrate of ACE (angiotensin converting enzyme) that removes a dipeptide to yield the physiologically active peptide angiotensin-2 (angiotensin 1-8). Angiotensin-1 and angiotensin-2 can be further processed to generate angiotensin-3 (angiotensin 2-8), angiotensin-4 (angiotensin 3-8). Angiotensin 1-7 is cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME (neprilysin). Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 Angiotensin-3 stimulates aldosterone release Angiotensin 1-7 is a ligand for the G-protein coupled receptor MAS1. Has vasodilator and antidiuretic effects. Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets
3D Structure