Protein AGT

URN urn:agi-llid:183
Name AGT
Description angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
Connectivity 2286
Notes 235T allele of angiotensinogen was also associated with an increased risk of presenting 3-vessel disease 235T allele of angiotensinogen was also associated with an increased risk of presenting 3-vessel disease. : In normal subjects the expression of local renin and angiotensinogen mRNA was organ specific, but with increase of the expression locally, the organ-specificity became lost in cirrhotic patients. A role for AGT in genetic susceptibility to preeclampsia. AGT M235T polymorphism does not confer any increased risk for MI in young South African Indians. AGT T174M polymorphism was associated with higher diastolic blood pressure levels in younger and non-overweight Japanese and was more evident among subjects with higher sodium intake. AGT expression in kidney proximal tubules adapts in the long-term to changes in glomerular filtration rate. ANG II activates rapamycin-sensitive mTOR signaling pathway in human coronary smooth muscle cells and involves activation of phosphatidylinositol 3-kinase, p70(S6k), and eukaryotic initiation factor-4E, leading to activation of protein synthesis. ANG II, via AT(1)R, modulates the secretion of TNF-alpha and MMP-2 from vascular endothelial cellsANG II, via AT(1)R, modulates the secretion of TNF-alpha and MMP-2 from endothelial cells and TNF-alpha mediates the effects of ANG II on MMP-2 release. ANG II-induced ROS generation plays a pivotal role in several pathophysiological situations, leading to renal growth regulation and remodeling after injury. Alcohol drinking might be specifically associated with the HNBP in M allele carriers of angiotensinogen gene T174M polymorphism. Ang II increased cytosolic Ca2+ release from Ca stores, enhanced calcineurin synthesis & activity, & stimulated NF-kappaB DNA-binding in cultured human neutrophils, demonstrating for the 1st time a stimulatory role of Ang II in phagocytic cell activation. Ang II stimulates IL-6 and IL-8 production and release from human adipocytes by a NF-kappaB-dependent pathway. This proinflammatory action of Ang II seems to be mediated by the AT1. AngII stimulates platelet superoxide production through activation of vascular NAD(P)H oxidase via the AT1 receptor and protein kinase C. Angiotensin II activates mineralocorticoid-receptor-mediated gene transcription via the AT1 receptor. Angiotensin II increases Pax-2 expression in fetal kidney cells via the AT2 receptor. Angiotensin II mediates the inflammatory gene expression effects of IL-18 by inducing the expression of the IL-18 receptor alpha subunit in vascular smooth muscle cells (VSMCs) via STAT-3 activation. Angiotensinogen 235T polymorphism is associated with blood pressure phenotypes. Angiotensinogen gene haplotypes are associated with hypertension and might act synergistically with I allele of the angiotensin-converting enzyme gene. CAML is an important signal transducer for the actions of Ang II in regulating the calcineurin-NFAT pathway and the interaction of CAML with ATRAP may mediate the Ang II actions in vascular physiology. Dissection of DNA cis elements that are demonstrably indispensable for regulating both the level and cell type specificity of hAGT gene transcription. Double homozygous combinations for normal alleles (MM of AGT, II of ACE and AA of AGTR1) had a lower risk of AMI (odds ratio<0.38), indicating a protective effect in these individuals. EGF and angiotensin II activation of phospholipase Cgamma through src is mediated by GIT1. Homozygosity of AGT M235T mutation is associated with high levels of cholesterol with no regard to the young age of patients with polycystic ovary syndrome. IL-6-inducible expression of the hAGT promoter is mediated by physical association of the COOH terminus of STAT3 with p300/CBP, the recruitment of which targets histone acetylation and results in chromatin remodeling. In this hypertensive population, the association of ACE inhibitor use with risk of nonfatal stroke varied by AGT genotype. There is a protective association between ACE inhibitor use and nonfatal stroke risk among individuals with ThrThr genotype of AGT. Increased plasma Ang-(1-7) in normal pregnant subjects compared with nonpregnant subjects and decreased Ang-(1-7) in preeclamptic subjects compared with normal pregnant subjects, consistent with the development of hypertension. Inreased premature coronary heart disease(CHD) risk is associated with higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a synergistic contribution of ACE DD and AGT MM polymorphisms to the development of premature CHD. Isolation of Ang II in supernatants of mononuclear leukocytes adds a further physiological source of Ang II to the current view of angiotensin metabolism. Release found under present conditions is at least sufficient to elicit vasoconstriction. Localization of expression in the nucleus of human astrocytes of CCF-STTG1 line. Locally generated Ang II amplifies the immunomediated inflammatory process of coronary microvessels occurring in unstable angina. Low-glomerular filtration rate cirrhotic patients had worse survival rate associated with more severe contraction of effective arterial blood volume, higher active renin /angiotensin II ratio and lower angiotensin-converting enzyme levels. M235 T polymorphism may be associated with persistent pulmonary hypertension in newborns with congenital diaphragmatic hernia. M235T and A(-20)C genotype of angiotensinogen can influence therapeutic efficacy of renin-angiotensin system blockade on renal survival in IgA nephropathy. Maternal and fetal angiotensinogen Thr235 genotypes are associated with an increased risk of intra-uterine growth retardation. No association was noted between the haplotypes of AGT gene and hypertension in tested people, but T235 allele might play an important role in increased risk for essential hypertension. No influence of angiotensinogen genetic polymorphisms in the development of lupus nephropathy. No significant differences in the distribution of any of these polymorphisms were found between patients with pre-eclampsia or eclampsia and the normal control. No statistically significant differences between groups were found in the allele frequency and genotype distribution for ACE and AGT polymorphisms. One angiotensinogen single nucleotide polymorphism (rs943580) significantly associated with transmitral early peak filling velocity in blacks; no haplotypes significantly associated with left ventricular phenotypes. Our results designate the C-532T and G-6A as the best candidates for functional studies on the AGT gene. PPARalpha and HNF-4 competitively affect the human angiotensinogen promoter through the C region. Patients homozygous for the T allele had a reduced carotid distensibility and an increased stiffness of the carotid wall material. Polymorphism in essential arterial hypertension in childhood. Polymorphism is associated with diabetic retinopathy in NIDDM in Chinese patients. Polymorphism is not associated with increased risk of developing chronic kidney allograft dysfunction. Polymorphism of the AGT M235T gene but not ACE I/D gene is associated with greater left ventricular mass index and relative wall thickness, indicating more concentric LVH, in Chinese peritoneal dialysis patients. Polymorphism of the promoter region of the angiotensinogen gene (ATG) and an angiotensin I-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism were studied in Kazakhs with hypertension and cardiovascular disease. Polymorphisms of genes encoding angiotensinogen as risk factors for orthostatic hypotension. Relationship of angiotensinogen single nucleotide polymorphisms with elevated blood pressure and risk of cardiovascular disease. Relationship of single-nucleotide polymorphisms of the angiotensinogen gene and susceptibility to hypertension. Results indicate that the AGT A(-6) allele frequency differs markedly between African Americans and white left ventricular hypertrophy individuals. Results suggest that connective tissue growth factor mediates angiotensin II-induced fibrosis in the heart and kidneys via blood pressure and calcineurin-dependent pathways. Results suggest that the polymorphism of A(-6)G in 5' upstream core promoter of the AGT gene may be involved in the pathogenesis of essential hypertension. Review. Angiotensin exerts mitogenic and growth promoting effects on cardiac myocytes and non-myocytic elements; and both of these effects significantly contribute to the development and progression of hypertensive heart disease. Significant association between the -217A variant of the AGT gene and hypertension. This variant plays a functional role in basal transcription of AGT, and may confer a risk for hypertension in Taiwanese populations. Significant association of AGT M235T with blood pressure and cholesterol metabolism in an Afro-Caribbean population in ""genetic context"" of RH blood group system. T174M polymorphism associated with higher risk of essential hypertension in people aged over 45. The AC/CC genotype of this polymorphism may be associated with an increased severity of proteinuria, suggesting that this polymorphism may play a significant role in the progression of IgA nephropathy in Japanese children. The ACE-I/D polymorphism is not associated with HAPE susceptibility in Japanese subjects. The AT(1)R gene polymorphisms may likely associate with HAPE susceptibility. The AGT A-20C genotypes may influence resting blood pressure (BP) response to strength training(ST). The Cl- -dependent effects of ANG II on Ca2+ transients may be mediated, at least in part, by a Cl- -dependent Ins(1,4,5)P3 accumulation in vascular smooth muscle cells. The M235 allele in exon 2 of the AGT gene, the G-6 and G-217 alleles in its promoter, & the corresponding haplotypes were associated with non-familial structural atrial fibrillation. The M235T polymorphism of the AGT gene is associated with MVPS in the Chinese population of Taiwan. The association of the TT genotype with MVPS is more noteworthy than an overall increase in the frequency of the T allele at the M235T locus. The M235T variant of the angiotensinogen gene and the body mass index are useful markers for prevention of hypertension in pregnancy: a tree-based analysis of gene-environment interaction. The prostate may be a source of the secreted angiotensin II found in seminal plasma. The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure and in the pathogenesis of essential hypertension and preeclampsia. Variants at two AGT sites together, in conjunction with age, may be significantly associated with elevated systolic blood pressure, whereas the single-site models are as good models of diastolic blood pressure. A molecular variant of ACE, but not angiotensinogen, gene is associated with preeclampsia in Korean women. Angiotensin II and lipopolysaccharide regulate the human tumor necrosis factor-alpha promoter in human cardiac fibroblasts. Angiotensin II may act on the pre-existing pancreatic arteries around neoplasms, leading to formation of hypovascular or avascular regions. Angiotensin II-dependent activation of steroidogenic acute regulatory protein transcription requires janus kinase 2 and calcium. Angiotensinogen (serine (or cysteine) peptidase inhibitor, clade A, member 8). Angiotensinogen (serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 8). Angiotensinogen M235T polymorphism was associated with adipocyte size in cultured adipocytes from obese subjects. Angiotensinogen T174M and M235T and the AT1-receptor A1166C polymorphisms were related to the change in LVH during antihypertensive treatment with an AT1-receptor antagonist. Autocrine/paracrine mechanism whereby angiotensin II, formed at adrenergic nerve endings in myocardial ischemia, elicits carrier-mediated norepinephrine release by activating adjacent AT(1) receptors. Common haplotype of the angiotensinogen gene is linked to angiotensinogen levels. Data fall short of showing significant association between a variant of the promoter of interleukin-1beta, polymorphism of angiotensinogen, and the missense variant of endothelial nitric oxide synthase and occurrence of idiopathic recurrent miscarriage. Data show that Ang II promotes coronary inflammation and remodeling, in part independent of blood pressure but dependent upon endothelin signal. Determine whether the M235T angiotensinogen (AGT) polymorphism, either interacting with habitual physical activity (PA) levels or independently, was associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. Dual production of renin and angiotensinogen in the renal proximal tubule can result in a systemic increase in arterial pressure. Findings suggest that obstructive sleep apnea mediates hypertension, at least in part, via a stimulation of angiotensin II production. Findings suggest that the AGT and angiotensin II type 1 receptor gene polymorphisms would not have an effect on hypertension or the end stage renal disease in autosomal dominant polycystic kidney disease. Gene polymorphisms in Turkish hypertensive patients. Human renin and human angiotensinogen have roles in development of hypertension in transgenic mice, and may predispose to spontaneous stroke. In hypertensive subjects with activated renin-angiotensin system, unopposed activity of angiotensin II is not involved in L-NAME-induced pressor and renal vasoconstrictor response. In patients with nephrotic syndrome due to biopsy proven focal segmental glomerulosclerosis, AGT-M235T polymorphism was associated with the severity of arterial hypertension. Lack of a significant effect of AGT M235T polymorphism on blood pressure level, but the difference in pulse pressure in the older population suggests that further investigations of this polymorphism should be made in the Japanese population. Leukocyte level strongly correlates with steady-state of plasma glucose concentration and significantly correlates with body mass index, plasma insulin, and leptin levels in essential hypertension; may be directly associated with insulin resistance. Neuronal AGT may play an important role in regulating salt intake and salt appetite. Polymorphism in angiogensinogen is associated with hypertension in African Americans. Rare variants in the promoter and coding regions are associated with different blood AGT levels. Relationship to intragraft messenger RNA expression of angiotensinogen and to chronic allograft nephropathy in kidney transplant patients. Results indicate that the change of vascular smooth muscle cells (VSMC) from contractile to synthetic phenotype sequentially increases expression of proteases, production of Ang II, and productions of growth factors, culminating in VSMC proliferation. Results suggest elevated glucose levels stimulate AII production via mechanisms dependent on glucose-induced PKC activation in mesangial cells and locally produced AII partly mediates the increase in mesangial matrix synthesis in high-glucose conditions. Results suggest that bile acids negatively regulate the human angiotensinogen gene through the inhibitory effect of small heterodimer partner on hepatocyte nuclear factor-4. Role of the M235T polymorphism in the AGT gene in modifying the blood pressure response to regular exercise. Single nucleotide polymorphism and haplotype structure in two populations, Japanese and white. Statistical evidence for the association of AGT promoter region with essential hypertension. Studies indicate that the angiotensin-converting enzyme-Angiotensin II-Angiotensin II receptor type 1 system serves as a positive feedback loop and fosters pulmonary artery adventitial fibroblasts proliferation under hypoxic conditions. Study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation. Study shows that the M235T variant in the gene encoding angiotensinogen could be a risk factor in mild and severe pre-eclampsia. The AGT-M235T gene did not contributeto QTc prolongation in end stage renal disease.

Swiss-Prot Accession B0ZBE2
B2R5S1
P01019
Q53GY3
Q53YY1
Q59EP2
Q86U78
Q3UTR7
P11859
Q8VCN0
P01015
Q5T0X3

Unigene ID Hs.19383
Mm.301626
Rn.6319

KEGG ID hsa:183
rno:24179
mmu:11606

Swiss-Prot ID ANGT_HUMAN
ANGT_RAT
B0ZBE2_HUMAN
B2R5S1_HUMAN
Q3UTR7_MOUSE

Cell Localization Extracellular

GO ID 0010698
0008083
0005179
0004867
0031702
0031703
0007199
0007200
0001998
0048143
0001568
0001974
0002035
0007267
0007160
0042756
0008065
0007588
0030198
0042445
0001822
0034374
0008285
0051387
0043524
0007263
0001543
0006800
0030432
0043410
0033864
0051092
0043065
0010613
0032270
0001819
0010595
0045742
0045723
0048146
0010744
0050729
0040018
0046622
0050731
0014068
0045940
0008217
0001558
0003078
0002019
0019229
0001999
0002018
0009409
0014873
0009651
0051145
0048659
0001658
0005737
0005576
0005615
0005625
0050880
0001991
0042310
0004937
0031701
0007186
0007202
0007166
0006883
0030147
0030308
0043085
0048169
0014061
0044444
0007565
0004866

Pathway AngiotensinR -> CREB/ELK-SRF/TP53 signaling
AngiotensinR -> STAT signaling
PPARbeta BCL6 Targets
Donna Regulators
PPARG Targets
FXR Targets
VDR Targets

IPI ID IPI00032220
IPI00654069
IPI00209744

Ariadne Ontology Neuromodulator

Mouse chromosome position 8 68.0 cM

GO Molecular Function hormone activity
growth factor activity
angiotensin receptor binding
type 1 angiotensin receptor binding
type 2 angiotensin receptor binding
acetyltransferase activator activity
serine-type endopeptidase inhibitor activity
alpha1-adrenergic receptor activity

Homologene ID 14

Hugo ID 333

GO Cellular Component extracellular region
soluble fraction
cytoplasm
cytoplasmic part
extracellular space

MGI ID 87963
2142488

Human chromosome position 1q42-q43

GO Biological Process cell-matrix adhesion
negative regulation of cell proliferation
negative regulation of cell growth
negative regulation of nerve growth factor receptor signaling pathway
negative regulation of neuron apoptosis
positive regulation of epidermal growth factor receptor signaling pathway
positive regulation of phosphoinositide 3-kinase cascade
positive regulation of MAPKKK cascade
positive regulation of apoptosis
positive regulation of foam cell differentiation
positive regulation of endothelial cell migration
positive regulation of fibroblast proliferation
positive regulation of cellular protein metabolic process
positive regulation of fatty acid biosynthetic process
positive regulation of steroid metabolic process
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of multicellular organism growth
positive regulation of organ growth
positive regulation of cytokine production
positive regulation of cardiac muscle hypertrophy
positive regulation of inflammatory response
regulation of cell growth
regulation of long-term neuronal synaptic plasticity
regulation of norepinephrine secretion
positive regulation of NF-kappaB transcription factor activity
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger
G-protein signaling, coupled to cGMP nucleotide second messenger
nitric oxide mediated signal transduction
regulation of natriuresis
regulation of vasoconstriction
regulation of blood pressure
cellular sodium ion homeostasis
natriuresis
angiotensin mediated vasoconstriction involved in regulation of systemic arterial blood pressure
brain renin-angiotensin system
regulation of systemic arterial blood pressure by circulatory renin-angiotensin
regulation of renal output by angiotensin
renin-angiotensin regulation of aldosterone production
renal response to blood flow during renin-angiotensin regulation of systemic arterial blood pressure
hormone metabolic process
regulation of blood vessel size
vasoconstriction
positive regulation of catalytic activity
activation of phospholipase C activity
positive regulation of NAD(P)H oxidase activity
astrocyte activation
cell-cell signaling
smooth muscle cell proliferation
extracellular matrix organization
low-density lipoprotein particle remodeling
establishment of blood-nerve barrier
smooth muscle cell differentiation
oxygen and reactive oxygen species metabolic process
ureteric bud branching
blood vessel remodeling
kidney development
ovarian follicle rupture
blood vessel development
excretion
response to muscle activity involved in regulation of muscle adaptation
peristalsis
drinking behavior
response to salt stress
response to cold

Rat chromosome position 19q12

GenBank ID NC_000001
NM_000029
NP_000020
NT_004559
NW_001838549
NW_927128
AC_000133
AC_000044
AL158214
CAI15356
AL512328
CAI14864
AY436323
AAR03501
CH471098
EAW69918
EAW69919
EU326304
ACA05910
M24689
AAA51679
S78529
AAD14287
S78530
AAD14288
X15324
CAA33385
AB209769
BAD93006
AK222798
BAD96518
AK222815
BAD96535
AK293507
BAG56991
AK303755
BAG64725
AK307978
AK312291
BAG35218
AU128714
AW128887
BC011519
AAH11519
BF338744
BT006851
AAP35497
CR591984
CR592799
CR595628
CR601683
CR606672
CR607896
CR607898
CR615493
CR615499
CR618295
CR618811
CR618903
CR619790
CR625369
CR625415
DC412932
K02215
AAA51731
M69110
AAA52282
T97863
W01494
P01019
Q53GY3
Q53YY1
Q59EP2
Q86U78
DQ891016
ABM81942
DQ894196
ABM85122
NC_000074
NM_007428
NP_031454
NT_078575
NW_001030904
AC_000030
AC126930
AF045883
AF045884
AAC01765
AF045885
AF045886
AF045887
CH466525
EDL11771
AK005354
AK018763
AK139179
BAE23913
BB869708
BC019496
AAH19496
BC028877
AAH28877
BC054387
AAH54387
BM899343
P11859
Q3UTR7
Q8VCN0
BC156111
AAI56112
BC156904
AAI56905
NC_005118
NM_134432
NP_602308
NW_047536
NW_001084745
AC_000087
CH474054
EDL96732
EDL96733
L00090
L00091
AAA98779
L00092
L00093
L00094
BC078741
AAH78741
BC087679
AAH87679
P01015
Q5T0X3
BG075626
NW_000349
BG088170

Group Neuromodulator
extracellular region
soluble fraction
cytoplasm
cytoplasmic part
extracellular space
hormone activity
growth factor activity
angiotensin receptor binding
type 1 angiotensin receptor binding
type 2 angiotensin receptor binding
acetyltransferase activator activity
serine-type endopeptidase inhibitor activity
alpha1-adrenergic receptor activity
cell-matrix adhesion
negative regulation of cell proliferation
negative regulation of cell growth
negative regulation of nerve growth factor receptor signaling pathway
negative regulation of neuron apoptosis
positive regulation of epidermal growth factor receptor signaling pathway
positive regulation of phosphoinositide 3-kinase cascade
positive regulation of MAPKKK cascade
positive regulation of apoptosis
positive regulation of foam cell differentiation
positive regulation of endothelial cell migration
positive regulation of fibroblast proliferation
positive regulation of cellular protein metabolic process
positive regulation of fatty acid biosynthetic process
positive regulation of steroid metabolic process
positive regulation of peptidyl-tyrosine phosphorylation
positive regulation of multicellular organism growth
positive regulation of organ growth
positive regulation of cytokine production
positive regulation of cardiac muscle hypertrophy
positive regulation of inflammatory response
regulation of cell growth
regulation of long-term neuronal synaptic plasticity
regulation of norepinephrine secretion
positive regulation of NF-kappaB transcription factor activity
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
activation of phospholipase C activity by G-protein coupled receptor protein signaling pathway coupled to IP3 second messenger
G-protein signaling, coupled to cGMP nucleotide second messenger
nitric oxide mediated signal transduction
regulation of natriuresis
regulation of vasoconstriction
regulation of blood pressure
cellular sodium ion homeostasis
natriuresis
angiotensin mediated vasoconstriction involved in regulation of systemic arterial blood pressure
brain renin-angiotensin system
regulation of systemic arterial blood pressure by circulatory renin-angiotensin
regulation of renal output by angiotensin
renin-angiotensin regulation of aldosterone production
renal response to blood flow during renin-angiotensin regulation of systemic arterial blood pressure
hormone metabolic process
regulation of blood vessel size
vasoconstriction
positive regulation of catalytic activity
activation of phospholipase C activity
positive regulation of NAD(P)H oxidase activity
astrocyte activation
cell-cell signaling
smooth muscle cell proliferation
extracellular matrix organization
low-density lipoprotein particle remodeling
establishment of blood-nerve barrier
smooth muscle cell differentiation
oxygen and reactive oxygen species metabolic process
ureteric bud branching
blood vessel remodeling
kidney development
ovarian follicle rupture
blood vessel development
excretion
response to muscle activity involved in regulation of muscle adaptation
peristalsis
drinking behavior
response to salt stress
response to cold

RGD ID 2069

LocusLink ID 183
11606
24179
102019

Alias ANHU
FLJ92595
FLJ97926
SERPINA8
angiotensinogen
angiotensin I
angiotensin II
OTTHUMP00000035878
pre-angiotensinogen
alpha-1 antiproteinase, antitrypsin
serine (or cysteine) proteinase inhibitor
Aogen
AI265500
angiotensin ll
Ang
PAT
ANRT
AngII
MGC105326
angiotensinogen (PAT)
angiotensinogen precursor
angiotensin
angiotensinogen (serine (or cysteine) proteinase inhibitor, clade A (alpha-
angiotensin II precursor
ANG II
5-Isoleucine-angiotensin II
angiotensin ii human
Angiotensin II, ile(5)-
Human angiotensin II
Isoleucine5-angiotensin II
ANG I
angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
AGT

Organism Homo sapiens
Mus musculus
Rattus norvegicus

OMIM ID 106150
145500
267430