Human Gene AGT (ENST00000366667.5)
  Description: Homo sapiens angiotensinogen (AGT), transcript variant 2, mRNA. (from RefSeq NM_001382817)
RefSeq Summary (NM_001384479): 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, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. 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. [provided by RefSeq, Nov 2019].
Gencode Transcript: ENST00000366667.5
Gencode Gene: ENSG00000135744.8
Transcript (Including UTRs)
   Position: hg38 chr1:230,702,523-230,714,122 Size: 11,600 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg38 chr1:230,703,141-230,710,850 Size: 7,710 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:230,702,523-230,714,122)mRNA (may differ from genome)Protein (485 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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LynxMGImyGene2neXtProtOMIMPubMed
ReactomeUniProtKB

-  Comments and Description Text from UniProtKB
  ID: ANGT_HUMAN
DESCRIPTION: RecName: Full=Angiotensinogen; AltName: Full=Serpin A8; Contains: RecName: Full=Angiotensin-1; AltName: Full=Angiotensin I; Short=Ang I; Contains: RecName: Full=Angiotensin-2; AltName: Full=Angiotensin II; Short=Ang II; Contains: RecName: Full=Angiotensin-3; AltName: Full=Angiotensin III; Short=Ang III; AltName: Full=Des-Asp[1]-angiotensin II; Flags: Precursor;
FUNCTION: Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis. In response to lowered blood pressure, the enzyme renin cleaves angiotensinogen to produce angiotensin-1 (angiotensin 1-10). 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.
FUNCTION: Angiotensin-2 acts directly on vascular smooth muscle as a potent vasoconstrictor, affects cardiac contractility and heart rate through its action on the sympathetic nervous system, and alters renal sodium and water absorption through its ability to stimulate the zona glomerulosa cells of the adrenal cortex to synthesize and secrete aldosterone.
FUNCTION: Angiotensin-3 stimulates aldosterone release.
FUNCTION: Angiotensin 1-7 is a ligand for the G-protein coupled receptor MAS1 (By similarity). Has vasodilator and antidiuretic effects (By similarity). Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets (By similarity).
SUBUNIT: During pregnancy, exists as a disulfide-linked 2:2 heterotetramer with the proform of PRG2 and as a complex (probably a 2:2:2 heterohexamer) with pro-PRG2 and C3dg.
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
PTM: 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.
DISEASE: Genetic variations in AGT are a cause of susceptibility to essential hypertension (EHT) [MIM:145500]. Essential hypertension is a condition in which blood pressure is consistently higher than normal with no identifiable cause.
DISEASE: Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
SIMILARITY: Belongs to the serpin family.
CAUTION: It is uncertain whether Met-1 or Met-10 is the initiator.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/AGT";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=AGT";
WEB RESOURCE: Name=Wikipedia; Note=Angiotensin entry; URL="http://en.wikipedia.org/wiki/Angiotensin";

-  MalaCards Disease Associations
  MalaCards Gene Search: AGT
Diseases sorted by gene-association score: renal tubular dysgenesis* (1625), hypertension, essential* (352), renal dysplasia* (231), renal tubular dysgenesis, agt-related* (100), cardiovascular disease risk factor )* (50), microvascular complications of diabetes 3 (13), anuria (12), pediatric hypertension (10), oligohydramnios (10), aortic valve disease 2 (10), malignant hypertension (9), familial sick sinus syndrome (9), gitelman syndrome (9), vesicoureteral reflux (9), diastolic heart failure (8), posterior urethral valves (8), chronic kidney failure (8), familial hypertension (8), hypertensive heart disease (8), mitral valve disease (8), muscle hypertrophy (7), placental abruption (6), otosclerosis (6), pre-eclampsia (6), sick sinus syndrome (6), interstitial nephritis (6), meningococcal infection (6), aldosteronism, glucocorticoid-remediable (6), end stage renal failure (6), aortic coarctation (6), hypercholesterolemia, familial (5), heart disease (5), fibromuscular dysplasia (5), atrial fibrillation (5), ischemic optic neuropathy (4), epileptic encephalopathy, childhood-onset (4), diabetes mellitus, insulin-dependent (4), hypotropia (4), diabetes mellitus, noninsulin-dependent (3), artery disease (3), autosomal dominant polycystic kidney disease (3), myocardial infarction (2), preeclampsia/eclampsia 1 (1), pulmonary fibrosis, idiopathic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 630.32 RPKM in Liver
Total median expression: 2204.85 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -8.0040-0.200 Picture PostScript Text
3' UTR -180.70618-0.292 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000227 - Angiotensngn
IPR023795 - Protease_inhib_I4_serpin_CS
IPR023796 - Serpin_dom
IPR000215 - Serpin_fam

Pfam Domains:
PF00079 - Serpin (serine protease inhibitor)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1N9U
- NMR

1N9V
- NMR

2JP8
- NMR
To conserve bandwidth, only the images from the first 3 structures are shown.
2WXW - X-ray MuPIT 2X0B - X-ray MuPIT 4FYS - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P01019
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
      
      
 RGDEnsembl   
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004867 serine-type endopeptidase inhibitor activity
GO:0005179 hormone activity
GO:0005515 protein binding
GO:0008083 growth factor activity
GO:0016176 superoxide-generating NADPH oxidase activator activity
GO:0017080 sodium channel regulator activity
GO:0031701 angiotensin receptor binding
GO:0031702 type 1 angiotensin receptor binding
GO:0031703 type 2 angiotensin receptor binding
GO:0048018 receptor agonist activity

Biological Process:
GO:0001558 regulation of cell growth
GO:0001819 positive regulation of cytokine production
GO:0001822 kidney development
GO:0001974 blood vessel remodeling
GO:0002016 regulation of blood volume by renin-angiotensin
GO:0002018 renin-angiotensin regulation of aldosterone production
GO:0002019 regulation of renal output by angiotensin
GO:0002027 regulation of heart rate
GO:0002034 regulation of blood vessel diameter by renin-angiotensin
GO:0003014 renal system process
GO:0003051 angiotensin-mediated drinking behavior
GO:0003081 regulation of systemic arterial blood pressure by renin-angiotensin
GO:0003331 positive regulation of extracellular matrix constituent secretion
GO:0006606 protein import into nucleus
GO:0006883 cellular sodium ion homeostasis
GO:0007166 cell surface receptor signaling pathway
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007199 G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger
GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007202 activation of phospholipase C activity
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007263 nitric oxide mediated signal transduction
GO:0007267 cell-cell signaling
GO:0007565 female pregnancy
GO:0007568 aging
GO:0008217 regulation of blood pressure
GO:0008284 positive regulation of cell proliferation
GO:0008306 associative learning
GO:0010469 regulation of receptor activity
GO:0010536 positive regulation of activation of Janus kinase activity
GO:0010595 positive regulation of endothelial cell migration
GO:0010613 positive regulation of cardiac muscle hypertrophy
GO:0010629 negative regulation of gene expression
GO:0010666 positive regulation of cardiac muscle cell apoptotic process
GO:0010744 positive regulation of macrophage derived foam cell differentiation
GO:0010873 positive regulation of cholesterol esterification
GO:0010951 negative regulation of endopeptidase activity
GO:0010976 positive regulation of neuron projection development
GO:0014061 regulation of norepinephrine secretion
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0014824 artery smooth muscle contraction
GO:0014873 response to muscle activity involved in regulation of muscle adaptation
GO:0016525 negative regulation of angiogenesis
GO:0019216 regulation of lipid metabolic process
GO:0019229 regulation of vasoconstriction
GO:0030308 negative regulation of cell growth
GO:0032270 positive regulation of cellular protein metabolic process
GO:0032355 response to estradiol
GO:0032930 positive regulation of superoxide anion generation
GO:0033864 positive regulation of NAD(P)H oxidase activity
GO:0034104 negative regulation of tissue remodeling
GO:0034374 low-density lipoprotein particle remodeling
GO:0035106 operant conditioning
GO:0035813 regulation of renal sodium excretion
GO:0035815 positive regulation of renal sodium excretion
GO:0038166 angiotensin-activated signaling pathway
GO:0042127 regulation of cell proliferation
GO:0042310 vasoconstriction
GO:0042311 vasodilation
GO:0042981 regulation of apoptotic process
GO:0043085 positive regulation of catalytic activity
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway
GO:0045777 positive regulation of blood pressure
GO:0045893 positive regulation of transcription, DNA-templated
GO:0048144 fibroblast proliferation
GO:0048146 positive regulation of fibroblast proliferation
GO:0048169 regulation of long-term neuronal synaptic plasticity
GO:0048659 smooth muscle cell proliferation
GO:0050663 cytokine secretion
GO:0050729 positive regulation of inflammatory response
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050880 regulation of blood vessel size
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051387 negative regulation of neurotrophin TRK receptor signaling pathway
GO:0051403 stress-activated MAPK cascade
GO:0051924 regulation of calcium ion transport
GO:0051969 regulation of transmission of nerve impulse
GO:0061049 cell growth involved in cardiac muscle cell development
GO:0061098 positive regulation of protein tyrosine kinase activity
GO:0070371 ERK1 and ERK2 cascade
GO:0070471 uterine smooth muscle contraction
GO:0071260 cellular response to mechanical stimulus
GO:0090190 positive regulation of branching involved in ureteric bud morphogenesis
GO:1901201 regulation of extracellular matrix assembly
GO:1902632 positive regulation of membrane hyperpolarization
GO:1903598 positive regulation of gap junction assembly
GO:1903779 regulation of cardiac conduction
GO:1904385 cellular response to angiotensin
GO:1904707 positive regulation of vascular smooth muscle cell proliferation
GO:1904754 positive regulation of vascular associated smooth muscle cell migration
GO:1905010 positive regulation of L-lysine import into cell
GO:1905589 positive regulation of L-arginine import across plasma membrane
GO:2000379 positive regulation of reactive oxygen species metabolic process
GO:2000650 negative regulation of sodium ion transmembrane transporter activity
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001275 positive regulation of glucose import in response to insulin stimulus

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0070062 extracellular exosome
GO:0072562 blood microparticle


-  Descriptions from all associated GenBank mRNAs
  K02215 - Human angiotensinogen mRNA, complete CDS.
AK222798 - Homo sapiens mRNA for angiotensinogen precursor variant, clone: HEP02859.
AK222815 - Homo sapiens mRNA for angiotensinogen precursor variant, clone: HEP05443.
AK293507 - Homo sapiens cDNA FLJ52255 complete cds, highly similar to Angiotensinogen precursor.
AB209769 - Homo sapiens mRNA for angiotensinogen precursor variant protein.
BC011519 - Homo sapiens angiotensinogen (serpin peptidase inhibitor, clade A, member 8), mRNA (cDNA clone MGC:17092 IMAGE:4213559), complete cds.
JD563396 - Sequence 544420 from Patent EP1572962.
JD534591 - Sequence 515615 from Patent EP1572962.
JD535585 - Sequence 516609 from Patent EP1572962.
JD228004 - Sequence 209028 from Patent EP1572962.
AK303755 - Homo sapiens cDNA FLJ53950 complete cds, highly similar to Angiotensinogen precursor.
JD133052 - Sequence 114076 from Patent EP1572962.
JD450302 - Sequence 431326 from Patent EP1572962.
JD230672 - Sequence 211696 from Patent EP1572962.
JD039592 - Sequence 20616 from Patent EP1572962.
JD176735 - Sequence 157759 from Patent EP1572962.
AK312291 - Homo sapiens cDNA, FLJ92595, highly similar to Homo sapiens angiotensinogen (serine (or cysteine) proteinaseinhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 8)(AGT), mRNA.
KJ896397 - Synthetic construct Homo sapiens clone ccsbBroadEn_05791 AGT gene, encodes complete protein.
KR709691 - Synthetic construct Homo sapiens clone CCSBHm_00005221 AGT (AGT) mRNA, encodes complete protein.
KR709692 - Synthetic construct Homo sapiens clone CCSBHm_00005224 AGT (AGT) mRNA, encodes complete protein.
KR709693 - Synthetic construct Homo sapiens clone CCSBHm_00005228 AGT (AGT) mRNA, encodes complete protein.
KR709694 - Synthetic construct Homo sapiens clone CCSBHm_00005229 AGT (AGT) mRNA, encodes complete protein.
BT006851 - Homo sapiens angiotensinogen (serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 8) mRNA, complete cds.
DQ891016 - Synthetic construct clone IMAGE:100003646; FLH168544.01X; RZPDo839A0794D angiotensinogen (serpin peptidase inhibitor, clade A, member 8) (AGT) gene, encodes complete protein.
DQ894196 - Synthetic construct Homo sapiens clone IMAGE:100008656; FLH168540.01L; RZPDo839A0793D angiotensinogen (serpin peptidase inhibitor, clade A, member 8) (AGT) gene, encodes complete protein.
AB222866 - Homo sapiens hFLT1 mRNA for fetal-liver predominant transporter 1, partial cds.
AB529142 - Synthetic construct DNA, clone: pF1KB5178, Homo sapiens AGT gene for angiotensinogen, without stop codon, in Flexi system.
AK307978 - Homo sapiens cDNA, FLJ97926.
M69110 - Human angiotensinogen mRNA, 5' end.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04270 - Vascular smooth muscle contraction
hsa04614 - Renin-angiotensin system
hsa05410 - Hypertrophic cardiomyopathy (HCM)

Reactome (by CSHL, EBI, and GO)

Protein P01019 (Reactome details) participates in the following event(s):

R-HSA-374173 Angiotensin II binds to angiotensin II receptor (types 1 and 2)
R-HSA-2022379 ACE2 hydrolyzes Angiotensin-(1-8) to Angiotensin-(1-7)
R-HSA-2022399 ENPEP hydrolyzes Angiotensin-(1-8) to Angiotensin-(2-8)
R-HSA-2022381 Cathepsin Z (Cathepsin X) hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2022383 Chymase hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2022405 ACE hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2022411 Cathepsin G hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2065355 Secreted ACE hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2022403 Renin:Prorenin Receptor hydrolyzes Angiotensinogen to Angiotensin-(1-10)
R-HSA-2022412 Renin hydrolyzes Angiotensinogen to Angiotensin-(1-10)
R-HSA-2065357 Prorenin:Prorenin Receptor hydrolyzes Angiotensinogen to Angiotensin-(1-10)
R-HSA-2022378 ACE2 hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-9)
R-HSA-2022396 Neprilysin hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-7)
R-HSA-2028294 Mast Cell Carboxypeptidase hydrolyzes Angiotensin-(1-10) to Yield Angiotensin-(1-9)
R-HSA-2022368 Neprilysin hydrolyzes Angiotensin-(1-9) to Angiotensin-(1-7)
R-HSA-2022398 ACE hydrolyzes Angiotensin-(1-9) to Angiotensin-(1-7)
R-NUL-2022369 ANPEP hydrolyzes Angiotensin III to Angiotensin IV
R-HSA-2022393 ANPEP hydrolyzes Angiotensin-(2-8) to Angiotensin-(3-8)
R-HSA-8851929 AOPEP:Zn2+ hydrolyses AGT(35-41) to AGT(36-41)
R-HSA-749454 The Ligand:GPCR:Gi complex dissociates
R-HSA-749452 The Ligand:GPCR:Gq complex dissociates
R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi
R-HSA-749448 Liganded Gq-activating GPCRs bind inactive heterotrimeric Gq
R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi
R-HSA-379048 Liganded Gq/11-activating GPCRs act as GEFs for Gq/11
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-1989781 PPARA activates gene expression
R-HSA-418594 G alpha (i) signalling events
R-HSA-416476 G alpha (q) signalling events
R-HSA-373076 Class A/1 (Rhodopsin-like receptors)
R-HSA-2980736 Peptide hormone metabolism
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-388396 GPCR downstream signalling
R-HSA-500792 GPCR ligand binding
R-HSA-392499 Metabolism of proteins
R-HSA-556833 Metabolism of lipids
R-HSA-372790 Signaling by GPCR
R-HSA-1430728 Metabolism
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: ANGT_HUMAN, ENST00000366667.1, ENST00000366667.2, ENST00000366667.3, ENST00000366667.4, NM_001382817, P01019, Q16358, Q16359, Q96F91, SERPINA8, uc001hty.1, uc001hty.2, uc001hty.3, uc001hty.4, uc001hty.5, uc001hty.6, uc001hty.7
UCSC ID: ENST00000366667.5
RefSeq Accession: NM_001384479
Protein: P01019 (aka ANGT_HUMAN)
CCDS: CCDS1585.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.