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FLASH GENE
Symbol AGT contributors: mct - updated : 19-11-2016
HGNC name angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
HGNC id 333
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
conjugated GlycoP
isoforms Precursor pre-angiotensinogen cleaved by renin then by ACE to generate angiotensin II
HOMOLOGY
interspecies homolog to murine Agt
Homologene
FAMILY
  • serpin family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    intracellular,cytoplasm
    basic FUNCTION
  • serine protease inhibitor involved in maintaining blood pressure and in the pathogenesis of essential HTA and preeclampsia
  • fundamental role for AGT/AGTR1 in age-induced vascular dysfunction
  • potential role of AGT in the modulation of retinal neurons and glia
  • involved in renal injury by inducing systemic or glomerular hypertension
  • regulating the activity of ERK5
  • has a crucial role in both the acute and chronic regulation of blood pressure
  • plays a role in the growth of AGTR1-positive breast cancer cells through PI3-kinase/Akt pathway activation
  • increases the permeability and plasmalemmal vesicle-1 (PV-1) expression of endothelial cells
  • plays a relevant role in perpetuating glomerular injury diabetic nephropathy via persistent activation of NOTCH1 and SNAI1 signaling in podocytes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cardiovascular
    text regulator of blood pressure
    PATHWAY
    metabolism
    signaling
  • AGT /ERK pathway has an important role in the production of MMP9 in human nonsyndromic thoracic aortic aneurysms (TAAs)
    • a component
  • activation of STAR gene is a critical component in the AGT-dependent increase in aldosterone biosynthesis in the adrenal gland
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • stimulating secretion of aldosterone promoting the release of ADH
  • NSEP1 to modulating AGT expression
  • interaction with EGFR (potent mitogen in renal cells)implicated in in progression of renal kidney disease
  • interacting with RREB1 by its binding elements in the 5'-flanking region
  • TTF1 plays potentially a role in the circadian rhythm regulation of the AGT gene expression via interacting with PER proteins
  • AGT may be involved in mediating load-induced activation of MGP expression
  • ELF3 is an AGT-inducible transcription factor that plays an important counter-regulatory role in the setting of vascular inflammation and remodeling
  • stimulates likely angiogenesis via transactivation of the EGF receptor, which promotes the phosphorylation of FLT1 and activation of SYK independent of VEGFA expression
  • BGLAP transforms adventitial fibroblasts to myofibroblasts through stimulating AGT release and subsequent activation of PKCD/TLR4/reactive oxygen species/cyclooxygenase-2 signaling cascade
  • AGT promotes apoptosis in intestinal epithelial cells through GATA6 and the Bax pathway in an AT2 receptor-dependent manner
  • melatonin directly ameliorates AGT-induced vascular endothelial damage partly via its antioxidative properties
  • RGN prevented cardiac hypertrophy and diastolic dysfunction by AGT
  • CEBPA binding initiates chromatin relaxation and transcription, which are followed by DNA demethylation around a CEBPA binding site and a transcription start site in the AGT promoter
  • AGT induced aggregation of RPL27 specifically in proximal tubules, again without apparent change in antiaggregating proteins or the aggresome–autophagosome markers
  • CAV1 plays a critical role for the development of abdominal aortic aneurysm at least in part via its specific alteration of AGT signalling within caveolae
  • MSR1 is critical for AGT-induced vascular remodeling by regulating macrophage polarization
  • AGT regulates ARHGDIA stability by SUMOylation and ubiquitination via AT1R activation and thus affects VSMC proliferation and vascular remodeling
    • cell & other
    REGULATION
    Other angiotensin II is regulated by ERP44, a factor involved in disulfide bond formation in the ER
    ASSOCIATED DISORDERS
    corresponding disease(s) RTD1
    Susceptibility
  • to chronic renal failure in patients with interstitial nephritis (ESRD)
  • to preeclampsia (PE)
  • to pediatric hypertrophic cardiomyopathy with poor outcome
  • to essential hypertension, AGT
  • vascular dementia
    • Variant & Polymorphism SNP , other
  • T235M
  • associated with progressive septal hypertrophy and left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy
  • T allele or TT homozygote is associated with the onset of ESRD in Caucasians
  • AGT M235T polymorphism is associated with PE in Chinese women
    • Candidate gene
    Marker
    Therapy target
  • targeting AGT/AGTR1 signaling could be a novel therapeutic for breast cancer )
    • ANIMAL & CELL MODELS