AGT

Protein identityUniProt · HPA

UniProt accession

P01019

Gene

AGT

Ensembl

ENSG00000135744

Chromosome

1

Canonical length

476 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

476 residues, UniProt reviewed canonical sequence.

>P01019|AGT
     1  MAPAGVSLRA TILCLLAWAG LAAGDRVYIH PFHLVIHNES TCEQLAKANA GKPKDPTFIP
    61  APIQAKTSPV DEKALQDQLV LVAAKLDTED KLRAAMVGML ANFLGFRIYG MHSELWGVVH
   121  GATVLSPTAV FGTLASLYLG ALDHTADRLQ AILGVPWKDK NCTSRLDAHK VLSALQAVQG
   181  LLVAQGRADS QAQLLLSTVV GVFTAPGLHL KQPFVQGLAL YTPVVLPRSL DFTELDVAAE
   241  KIDRFMQAVT GWKTGCSLMG ASVDSTLAFN TYVHFQGKMK GFSLLAEPQE FWVDNSTSVS
   301  VPMLSGMGTF QHWSDIQDNF SVTQVPFTES ACLLLIQPHY ASDLDKVEGL TFQQNSLNWM
   361  KKLSPRTIHL TMPQLVLQGS YDLQDLLAQA ELPAILHTEL NLQKLSNDRI RVGEVLNSIF
   421  FELEADEREP TESTQQLNKP EVLEVTLNRP FLFAVYDQSA TALHFLGRVA NPLSTA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AGT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

1,555 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AGT.

Disease | AllUniProt

Conditions AGT is implicated in, by any mechanism.

• Essential hypertension (EHT) MIM:145500
• Renal tubular dysgenesis (RTD) MIM:267430

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 266 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Renal tubular dysgenesis of genetic origin
• Renal tubular dysgenesis
• Essential hypertension, genetic
• Anhydramnios
• Large fontanelles

Disease | AutoantibodyPubMed

Conditions in which antibodies against AGT are reported. Each links to that disease's full target list.

• Pre-Eclampsia 31
• Hypertension 14
• COVID-19 7
• Scleroderma, Systemic 4

Showing 4 of 5 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for AGT from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.45

gnomAD pLI

0

gnomAD missense Z

-0.2

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiotensin-activated signaling pathway
• blood vessel remodeling
• cell-cell signaling
• G protein-coupled receptor signaling pathway
• G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger
• kidney development
• low-density lipoprotein particle remodeling
• maintenance of blood vessel diameter homeostasis by renin-angiotensin
• negative regulation of MAP kinase activity
• negative regulation of neurotrophin TRK receptor signaling pathway
• nitric oxide-cGMP-mediated signaling
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of branching involved in ureteric bud morphogenesis
• positive regulation of cardiac muscle hypertrophy
• positive regulation of cholesterol metabolic process
• positive regulation of cytokine production
• positive regulation of DNA-templated transcription
• positive regulation of endothelial cell migration
• positive regulation of epidermal growth factor receptor signaling pathway
• positive regulation of epithelial to mesenchymal transition
• positive regulation of extracellular matrix assembly
• positive regulation of extrinsic apoptotic signaling pathway
• positive regulation of fibroblast proliferation
• positive regulation of gap junction assembly
• positive regulation of inflammatory response
• positive regulation of macrophage derived foam cell differentiation
• positive regulation of miRNA transcription
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of reactive oxygen species metabolic process
• regulation of apoptotic process
• regulation of blood pressure
• regulation of cardiac conduction
• regulation of cell growth
• regulation of cell population proliferation
• regulation of extracellular matrix assembly
• regulation of renal output by angiotensin
• regulation of renal sodium excretion
• regulation of vasoconstriction
• renal system process
• renin-angiotensin regulation of aldosterone production
• response to angiotensin
• response to muscle activity involved in regulation of muscle adaptation
• vasoconstriction
• regulation of blood volume by renin-angiotensin

Molecular functions

• growth factor activity
• hormone activity
• serine-type endopeptidase inhibitor activity
• type 1 angiotensin receptor binding
• type 2 angiotensin receptor binding

Cellular components

• blood microparticle
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Serpin family
• Serpin, conserved site
• Serpin domain
• Serpin superfamily
• Serpin superfamily, domain 1
• Serpin superfamily, domain 2
• Serpin (serine protease inhibitor)
• Angiotensinogen
• Angiotensinogen, serpin domain

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Secreted
• Signal
• Vasoactive
• Vasoconstrictor

InteractionsUniProt · HPA

Protein binding partners of AGT in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• REN