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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
Corresponding disease
RTD1 renal tubular dysgenesis 1
Location 1q42.2      Physical location : 230.838.273 - 230.850.336
Synonym name
  • angiotensin I
  • angiotensin II
  • serine (or cysteine) proteinase inhibitor
  • serpin A8
  • angiotensinogen (serine (or cysteine) proteinase inhibitor, (clade A member 8)
  • alpha-1 antiproteinase, antitrypsin
  • Synonym symbol(s) SERPINA8, ANHU, FLJ92595, FLJ97926, ANG2
    DNA
    TYPE functioning gene
    STRUCTURE 12.07 kb     5 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • a regulatory element at the 3'-downstream region
  • 5'-flanking region in the promoter identified the GGATGG-like elements
  • activation of the AGT promoter in hepatocytes through the IL6/STAT3 signaling mechanism
  • high-affinity HNF4A binding sites in its promoter
  • CEBP binding site in the promoter was hypomethylated in tissues with high expression of AGT, but not in those with low expression
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2587 49.8 485 - 2006 16949687
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   predominantly
    Nervousbrain   highly
    Urinarykidneytubuleconvoluted tubuleproximal tubule  Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte
    Urinaryepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion serum, plasma
    at STAGE
    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