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Protein

Angiotensinogen

Gene

AGT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
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.
Angiotensin-3: stimulates aldosterone release.
Angiotensin 1-7: is a ligand for the G-protein coupled receptor MAS1. Has vasodilator and antidiuretic effects. Has an antithrombotic effect that involves MAS1-mediated release of nitric oxide from platelets.By similarity3 Publications

Caution

It is uncertain whether Met-1 or Met-10 is the initiator.Curated

GO - Molecular functioni

  • growth factor activity Source: BHF-UCL
  • hormone activity Source: BHF-UCL
  • receptor ligand activity Source: BHF-UCL
  • serine-type endopeptidase inhibitor activity Source: ProtInc
  • sodium channel regulator activity Source: BHF-UCL
  • superoxide-generating NADPH oxidase activator activity Source: BHF-UCL
  • type 1 angiotensin receptor binding Source: BHF-UCL
  • type 2 angiotensin receptor binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionVasoactive, Vasoconstrictor

Enzyme and pathway databases

ReactomeiR-HSA-1989781 PPARA activates gene expression
R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-416476 G alpha (q) signalling events
R-HSA-418594 G alpha (i) signalling events
SIGNORiP01019

Protein family/group databases

MEROPSiI04.953

Names & Taxonomyi

Protein namesi
Recommended name:
Angiotensinogen
Alternative name(s):
Serpin A8
Cleaved into the following 8 chains:
Alternative name(s):
Angiotensin 1-10
Angiotensin I
Short name:
Ang I
Alternative name(s):
Angiotensin 1-8
Angiotensin II
Short name:
Ang II
Alternative name(s):
Angiotensin 2-8
Angiotensin III
Short name:
Ang III
Des-Asp[1]-angiotensin II
Alternative name(s):
Angiotensin 3-8
Angiotensin IV
Short name:
Ang IV
Gene namesi
Name:AGT
Synonyms:SERPINA8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000135744.7
HGNCiHGNC:333 AGT
MIMi106150 gene
neXtProtiNX_P01019

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Essential hypertension (EHT)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA condition in which blood pressure is consistently higher than normal with no identifiable cause.
See also OMIM:145500
Renal tubular dysgenesis (RTD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal 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).
See also OMIM:267430
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035433375R → Q in RTD. 1 PublicationCorresponds to variant dbSNP:rs74315283EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi183
MalaCardsiAGT
MIMi145500 phenotype
267430 phenotype
OpenTargetsiENSG00000135744
Orphaneti243761 Essential hypertension
97369 Renal tubular dysgenesis of genetic origin
PharmGKBiPA42

Chemistry databases

ChEMBLiCHEMBL3596085
DrugBankiDB05206 PS433540

Polymorphism and mutation databases

BioMutaiAGT
DMDMi113880

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 333 PublicationsAdd BLAST33
ChainiPRO_000003245634 – 485AngiotensinogenAdd BLAST452
PeptideiPRO_000003245734 – 43Angiotensin-110
PeptideiPRO_000042065934 – 42Angiotensin 1-99
PeptideiPRO_000003245834 – 41Angiotensin-28
PeptideiPRO_000042066034 – 40Angiotensin 1-77
PeptideiPRO_000042066134 – 38Angiotensin 1-55
PeptideiPRO_000042066234 – 37Angiotensin 1-44
PeptideiPRO_000003245935 – 41Angiotensin-37
PeptideiPRO_000042066336 – 41Angiotensin-46

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34Beta-decarboxylated aspartate; in form angiotensin-A1 Publication1
Glycosylationi47N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi51 ↔ 1711 Publication
Glycosylationi170N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi304N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi328N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

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.1 Publication
In response to low blood pressure, the enzyme renin/REN cleaves angiotensinogen to produce angiotensin-1. Angiotensin-1 is a substrate of ACE (angiotensin converting enzyme) that removes a dipeptide to yield the physiologically active peptide angiotensin-2. Angiotensin-1 and angiotensin-2 can be further processed to generate angiotensin-3, angiotensin-4. Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4. Angiotensin 1-7 has also been proposed to be cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME (neprilysin).2 Publications
The disulfide bond is labile. Angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized disulfide-bonded form, which preferentially interacts with receptor-bound renin.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP01019
MaxQBiP01019
PaxDbiP01019
PeptideAtlasiP01019
PRIDEiP01019
ProteomicsDBi51306

2D gel databases

SWISS-2DPAGEiP01019

PTM databases

CarbonylDBiP01019
GlyConnecti703
iPTMnetiP01019
PhosphoSitePlusiP01019

Miscellaneous databases

PMAP-CutDBiP01019

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

BgeeiENSG00000135744 Expressed in 211 organ(s), highest expression level in liver
CleanExiHS_AGT
ExpressionAtlasiP01019 baseline and differential
GenevisibleiP01019 HS

Organism-specific databases

HPAiCAB025798
HPA001557

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106690, 15 interactors
CORUMiP01019
DIPiDIP-309N
IntActiP01019, 10 interactors
MINTiP01019
STRINGi9606.ENSP00000355627

Structurei

Secondary structure

1485
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP01019
SMRiP01019
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01019

Family & Domainsi

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00890000139531
HOVERGENiHBG004233
InParanoidiP01019
KOiK09821
OMAiRFMQAVT
OrthoDBiEOG091G077M
PhylomeDBiP01019
TreeFamiTF343201

Family and domain databases

CDDicd02054 angiotensinogen, 1 hit
InterProiView protein in InterPro
IPR000227 Angiotensinogen
IPR033834 Angiotensinogen_serpin
IPR023795 Serpin_CS
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PTHR11461:SF13 PTHR11461:SF13, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
PRINTSiPR00654 ANGIOTENSNGN
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit
PROSITEiView protein in PROSITE
PS00284 SERPIN, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01019-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MRKRAPQSEM APAGVSLRAT ILCLLAWAGL AAGDRVYIHP FHLVIHNEST
60 70 80 90 100
CEQLAKANAG KPKDPTFIPA PIQAKTSPVD EKALQDQLVL VAAKLDTEDK
110 120 130 140 150
LRAAMVGMLA NFLGFRIYGM HSELWGVVHG ATVLSPTAVF GTLASLYLGA
160 170 180 190 200
LDHTADRLQA ILGVPWKDKN CTSRLDAHKV LSALQAVQGL LVAQGRADSQ
210 220 230 240 250
AQLLLSTVVG VFTAPGLHLK QPFVQGLALY TPVVLPRSLD FTELDVAAEK
260 270 280 290 300
IDRFMQAVTG WKTGCSLMGA SVDSTLAFNT YVHFQGKMKG FSLLAEPQEF
310 320 330 340 350
WVDNSTSVSV PMLSGMGTFQ HWSDIQDNFS VTQVPFTESA CLLLIQPHYA
360 370 380 390 400
SDLDKVEGLT FQQNSLNWMK KLSPRTIHLT MPQLVLQGSY DLQDLLAQAE
410 420 430 440 450
LPAILHTELN LQKLSNDRIR VGEVLNSIFF ELEADEREPT ESTQQLNKPE
460 470 480
VLEVTLNRPF LFAVYDQSAT ALHFLGRVAN PLSTA
Length:485
Mass (Da):53,154
Last modified:July 21, 1986 - v1
Checksum:i5026C2DFB2DD236E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti51C → S AA sequence (PubMed:7259779).Curated1
Sequence conflicti58N → D AA sequence (PubMed:7259779).Curated1
Sequence conflicti333Q → E in AAA51679 (PubMed:2924688).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02293343L → F Associated with susceptibility to pre-eclampsia; alters the reactions with renin and angiotensin-converting enzyme. 1 PublicationCorresponds to variant dbSNP:rs41271499Ensembl.1
Natural variantiVAR_02916698E → K. Corresponds to variant dbSNP:rs11568032Ensembl.1
Natural variantiVAR_051939114G → C. Corresponds to variant dbSNP:rs2229389Ensembl.1
Natural variantiVAR_035431137T → M. Corresponds to variant dbSNP:rs34829218Ensembl.1
Natural variantiVAR_007093207T → M Associated with hypertension. 1 PublicationCorresponds to variant dbSNP:rs4762EnsemblClinVar.1
Natural variantiVAR_007094242T → I Associated with susceptibility to hypertension. 1 PublicationCorresponds to variant dbSNP:rs765678426Ensembl.1
Natural variantiVAR_007095244L → R Associated with susceptibility to hypertension. 1 PublicationCorresponds to variant dbSNP:rs5041Ensembl.1
Natural variantiVAR_029167268M → I. Corresponds to variant dbSNP:rs11568053Ensembl.1
Natural variantiVAR_007096268M → T Associated with essential hypertension and pre-eclampsia. 2 PublicationsCorresponds to variant dbSNP:rs699EnsemblClinVar.1
Natural variantiVAR_007097281Y → C Associated with susceptibility to hypertension; alters the structure, glycosylation and secretion of angiotensinogen. 3 PublicationsCorresponds to variant dbSNP:rs56073403Ensembl.1
Natural variantiVAR_035432335P → S1 PublicationCorresponds to variant dbSNP:rs17856352Ensembl.1
Natural variantiVAR_035433375R → Q in RTD. 1 PublicationCorresponds to variant dbSNP:rs74315283EnsemblClinVar.1
Natural variantiVAR_014573392L → M. Corresponds to variant dbSNP:rs1805090Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02215 mRNA Translation: AAA51731.1
M24689
, M24686, M24687, M24688 Genomic DNA Translation: AAA51679.1
X15324
, X15325, X15326, X15327 Genomic DNA Translation: CAA33385.1
BC011519 mRNA Translation: AAH11519.1
M69110 mRNA Translation: AAA52282.1
S78529 Genomic DNA Translation: AAD14287.1
S78530 Genomic DNA Translation: AAD14288.1
CCDSiCCDS1585.1
PIRiA35203 ANHU
RefSeqiNP_000020.1, NM_000029.3
UniGeneiHs.19383

Genome annotation databases

EnsembliENST00000366667; ENSP00000355627; ENSG00000135744
GeneIDi183
KEGGihsa:183
UCSCiuc001hty.6 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Angiotensin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02215 mRNA Translation: AAA51731.1
M24689
, M24686, M24687, M24688 Genomic DNA Translation: AAA51679.1
X15324
, X15325, X15326, X15327 Genomic DNA Translation: CAA33385.1
BC011519 mRNA Translation: AAH11519.1
M69110 mRNA Translation: AAA52282.1
S78529 Genomic DNA Translation: AAD14287.1
S78530 Genomic DNA Translation: AAD14288.1
CCDSiCCDS1585.1
PIRiA35203 ANHU
RefSeqiNP_000020.1, NM_000029.3
UniGeneiHs.19383

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N9UNMR-A34-43[»]
1N9VNMR-A34-41[»]
2JP8NMR-P34-40[»]
2WXWX-ray3.30A34-485[»]
2X0BX-ray4.33B/D/F/H34-485[»]
3CK0X-ray3.00P34-41[»]
3WOOX-ray1.80C/D36-41[»]
3WORX-ray2.10C/D34-41[»]
4AA1X-ray1.99P34-41[»]
4APHX-ray1.99P34-41[»]
4FYSX-ray2.01C36-41[»]
5E2QX-ray2.40B34-41[»]
5M3XX-ray2.63A/B44-485[»]
5M3YX-ray2.30A34-485[»]
ProteinModelPortaliP01019
SMRiP01019
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106690, 15 interactors
CORUMiP01019
DIPiDIP-309N
IntActiP01019, 10 interactors
MINTiP01019
STRINGi9606.ENSP00000355627

Chemistry databases

ChEMBLiCHEMBL3596085
DrugBankiDB05206 PS433540

Protein family/group databases

MEROPSiI04.953

PTM databases

CarbonylDBiP01019
GlyConnecti703
iPTMnetiP01019
PhosphoSitePlusiP01019

Polymorphism and mutation databases

BioMutaiAGT
DMDMi113880

2D gel databases

SWISS-2DPAGEiP01019

Proteomic databases

EPDiP01019
MaxQBiP01019
PaxDbiP01019
PeptideAtlasiP01019
PRIDEiP01019
ProteomicsDBi51306

Protocols and materials databases

DNASUi183
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366667; ENSP00000355627; ENSG00000135744
GeneIDi183
KEGGihsa:183
UCSCiuc001hty.6 human

Organism-specific databases

CTDi183
DisGeNETi183
EuPathDBiHostDB:ENSG00000135744.7
GeneCardsiAGT
HGNCiHGNC:333 AGT
HPAiCAB025798
HPA001557
MalaCardsiAGT
MIMi106150 gene
145500 phenotype
267430 phenotype
neXtProtiNX_P01019
OpenTargetsiENSG00000135744
Orphaneti243761 Essential hypertension
97369 Renal tubular dysgenesis of genetic origin
PharmGKBiPA42
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00890000139531
HOVERGENiHBG004233
InParanoidiP01019
KOiK09821
OMAiRFMQAVT
OrthoDBiEOG091G077M
PhylomeDBiP01019
TreeFamiTF343201

Enzyme and pathway databases

ReactomeiR-HSA-1989781 PPARA activates gene expression
R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-375276 Peptide ligand-binding receptors
R-HSA-416476 G alpha (q) signalling events
R-HSA-418594 G alpha (i) signalling events
SIGNORiP01019

Miscellaneous databases

ChiTaRSiAGT human
EvolutionaryTraceiP01019
GeneWikiiAngiotensin
GenomeRNAii183
PMAP-CutDBiP01019
PROiPR:P01019
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135744 Expressed in 211 organ(s), highest expression level in liver
CleanExiHS_AGT
ExpressionAtlasiP01019 baseline and differential
GenevisibleiP01019 HS

Family and domain databases

CDDicd02054 angiotensinogen, 1 hit
InterProiView protein in InterPro
IPR000227 Angiotensinogen
IPR033834 Angiotensinogen_serpin
IPR023795 Serpin_CS
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PTHR11461:SF13 PTHR11461:SF13, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
PRINTSiPR00654 ANGIOTENSNGN
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit
PROSITEiView protein in PROSITE
PS00284 SERPIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiANGT_HUMAN
AccessioniPrimary (citable) accession number: P01019
Secondary accession number(s): Q16358, Q16359, Q96F91
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: September 12, 2018
This is version 218 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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