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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000029 5 - 2587 NP_000020 49.8 485 - 2006 16949687

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive liver       predominantly Nervous brain       highly Urinary kidney tubule convoluted tubule proximal tubule   Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose

cells

System Cell Pubmed Species Stage Rna symbol Digestive hepatocyte Urinary epithelial 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