ID ANGT_HUMAN Reviewed; 485 AA. AC P01019; Q16358; Q16359; Q96F91; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 13-FEB-2019, entry version 222. DE RecName: Full=Angiotensinogen; DE AltName: Full=Serpin A8; DE Contains: DE RecName: Full=Angiotensin-1; DE AltName: Full=Angiotensin 1-10; DE AltName: Full=Angiotensin I; DE Short=Ang I; DE Contains: DE RecName: Full=Angiotensin-2; DE AltName: Full=Angiotensin 1-8; DE AltName: Full=Angiotensin II; DE Short=Ang II; DE Contains: DE RecName: Full=Angiotensin-3; DE AltName: Full=Angiotensin 2-8; DE AltName: Full=Angiotensin III; DE Short=Ang III; DE AltName: Full=Des-Asp[1]-angiotensin II; DE Contains: DE RecName: Full=Angiotensin-4; DE AltName: Full=Angiotensin 3-8; DE AltName: Full=Angiotensin IV; DE Short=Ang IV; DE Contains: DE RecName: Full=Angiotensin 1-9; DE Contains: DE RecName: Full=Angiotensin 1-7; DE Contains: DE RecName: Full=Angiotensin 1-5; DE Contains: DE RecName: Full=Angiotensin 1-4; DE Flags: Precursor; GN Name=AGT; Synonyms=SERPINA8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6089875; DOI=10.1021/bi00311a006; RA Kageyama R., Ohkubo H., Nakanishi S.; RT "Primary structure of human preangiotensinogen deduced from the cloned RT cDNA sequence."; RL Biochemistry 23:3603-3609(1984). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2924688; DOI=10.1089/dna.1.1989.8.87; RA Gaillard I., Clauser E., Corvol P.; RT "Structure of human angiotensinogen gene."; RL DNA 8:87-99(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1692023; RA Fukamizu A., Takahashi S., Seo M.S., Tada M., Tanimoto K., Uehara S., RA Murakami K.; RT "Structure and expression of the human angiotensinogen gene. RT Identification of a unique and highly active promoter."; RL J. Biol. Chem. 265:7576-7582(1990). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-335. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-338. RX PubMed=2885106; DOI=10.1161/01.RES.60.5.786; RA Kunapuli S.P., Kumar A.; RT "Molecular cloning of human angiotensinogen cDNA and evidence for the RT presence of its mRNA in rat heart."; RL Circ. Res. 60:786-790(1987). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 32-184. RX PubMed=3579322; DOI=10.1016/0003-9861(87)90148-2; RA Kunapuli S.P., Benedict C.R., Kumar A.; RT "Tissue specific hormonal regulation of the rat angiotensinogen gene RT expression."; RL Arch. Biochem. Biophys. 254:642-646(1987). RN [7] RP PROTEIN SEQUENCE OF 34-58. RX PubMed=7259779; DOI=10.1016/0006-291X(81)90762-2; RA Tewksbury D.A., Dart R.A., Travis J.; RT "The amino terminal amino acid sequence of human angiotensinogen."; RL Biochem. Biophys. Res. Commun. 99:1311-1315(1981). RN [8] RP PROTEIN SEQUENCE OF 34-45, AND SUBUNIT. RC TISSUE=Serum; RX PubMed=7539791; DOI=10.1074/jbc.270.23.13645; RA Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., RA Stigbrand T., Gleich G.J., Sottrup-Jensen L.; RT "Identification of angiotensinogen and complement C3dg as novel RT proteins binding the proform of eosinophil major basic protein in RT human pregnancy serum and plasma."; RL J. Biol. Chem. 270:13645-13651(1995). RN [9] RP PROTEIN SEQUENCE OF 34-43. RX PubMed=4300938; RA Arakawa K., Minohara A., Yamada J., Nakamura M.; RT "Enzymatic degradation and electrophoresis of human angiotensin I."; RL Biochim. Biophys. Acta 168:106-112(1968). RN [10] RP GLYCOSYLATION AT ASN-47; ASN-170; ASN-304 AND ASN-328. RX PubMed=3934016; DOI=10.1016/0303-7207(85)90039-5; RA Campbell D.J., Bouhnik J., Coezy E., Menard J., Corvol P.; RT "Processing of rat and human angiotensinogen precursors by microsomal RT membranes."; RL Mol. Cell. Endocrinol. 43:31-40(1985). RN [11] RP FUNCTION OF ANGIOTENSIN-3. RX PubMed=1132082; DOI=10.1161/01.RES.36.6.38; RA Goodfriend T.L., Peach M.J.; RT "Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and RT speculation for its role as an important agonist in the renin RT - angiotensin system."; RL Circ. Res. 36:38-48(1975). RN [12] RP FUNCTION OF ANGIOTENSIN-2. RX PubMed=10619573; DOI=10.1016/S0895-7061(99)00103-X; RA Weir M.R., Dzau V.J.; RT "The renin-angiotensin-aldosterone system: a specific target for RT hypertension management."; RL Am. J. Hypertens. 12:205S-213S(1999). RN [13] RP CLEAVAGE BY ACE AND ACE2. RX PubMed=10969042; DOI=10.1161/01.RES.87.5.e1; RA Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., RA Stagliano N., Donovan M., Woolf B., Robison K., Jeyaseelan R., RA Breitbart R.E., Acton S.; RT "A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) RT converts angiotensin I to angiotensin 1-9."; RL Circ. Res. 87:E1-E9(2000). RN [14] RP CLEAVAGE OF ANGIOTENSIN-1 AND ANGIOTENSIN-2 BY ACE2. RX PubMed=11815627; DOI=10.1074/jbc.M200581200; RA Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., RA Godbout K., Parsons T., Baronas E., Hsieh F., Acton S., Patane M.A., RA Nichols A., Tummino P.; RT "Hydrolysis of biological peptides by human angiotensin-converting RT enzyme-related carboxypeptidase."; RL J. Biol. Chem. 277:14838-14843(2002). RN [15] RP ANGIOTENSIN PEPTIDES METABOLISM. RX PubMed=15283675; DOI=10.1042/BJ20040634; RA Rice G.I., Thomas D.A., Grant P.J., Turner A.J., Hooper N.M.; RT "Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 RT and neprilysin in angiotensin peptide metabolism."; RL Biochem. J. 383:45-51(2004). RN [16] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-47. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., RA Moore R.J., Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [17] RP DECARBOXYLATION AT ASP-34, FUNCTION, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=17138938; DOI=10.1161/01.ATV.0000253889.09765.5f; RA Jankowski V., Vanholder R., van der Giet M., Tolle M., Karadogan S., RA Gobom J., Furkert J., Oksche A., Krause E., Tran T.N., Tepel M., RA Schuchardt M., Schluter H., Wiedon A., Beyermann M., Bader M., RA Todiras M., Zidek W., Jankowski J.; RT "Mass-spectrometric identification of a novel angiotensin peptide in RT human plasma."; RL Arterioscler. Thromb. Vasc. Biol. 27:297-302(2007). RN [18] RP REVIEW ON THE RENIN-ANGIOTENSIN SYSTEM. RX PubMed=18793332; DOI=10.1111/j.1365-2796.2008.01981.x; RA Fyhrquist F., Saijonmaa O.; RT "Renin-angiotensin system revisited."; RL J. Intern. Med. 264:224-236(2008). RN [19] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-47. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP STRUCTURE BY NMR OF ANGIOTENSIN-2. RX PubMed=9492317; DOI=10.1046/j.1432-1327.1998.2510448.x; RA Carpenter K.A., Wilkes B.C., Schiller P.W.; RT "The octapeptide angiotensin II adopts a well-defined structure in a RT phospholipid environment."; RL Eur. J. Biochem. 251:448-453(1998). RN [23] RP STRUCTURE BY NMR OF 34-43, AND STRUCTURE BY NMR OF 34-41. RX PubMed=12752436; DOI=10.1046/j.1432-1033.2003.03573.x; RA Spyroulias G.A., Nikolakopoulou P., Tzakos A., Gerothanassis I.P., RA Magafa V., Manessi-Zoupa E., Cordopatis P.; RT "Comparison of the solution structures of angiotensin I & II. RT Implication for structure-function relationship."; RL Eur. J. Biochem. 270:2163-2173(2003). RN [24] RP X-RAY CRYSTALLOGRAPHY (4.33 ANGSTROMS) OF 34-485 IN COMPLEX WITH RP RENIN, AND DISULFIDE BOND. RX PubMed=20927107; DOI=10.1038/nature09505; RA Zhou A., Carrell R.W., Murphy M.P., Wei Z., Yan Y., Stanley P.L., RA Stein P.E., Broughton Pipkin F., Read R.J.; RT "A redox switch in angiotensinogen modulates angiotensin release."; RL Nature 468:108-111(2010). RN [25] RP VARIANTS MET-207; THR-268 AND CYS-281. RX PubMed=1394429; DOI=10.1016/0092-8674(92)90275-H; RA Jeunemaitre X., Soubrier F., Kotelevtsev Y.V., Lifton R.P., RA Williams C.S., Charru A., Hunt S.C., Hopkins P.N., Williams R.R., RA Lalouel J.-M., Corvol P.; RT "Molecular basis of human hypertension: role of angiotensinogen."; RL Cell 71:169-180(1992). RN [26] RP VARIANT THR-268. RX PubMed=8513325; DOI=10.1038/ng0593-59; RA Ward K., Hata A., Jeunemaitre X., Helin C., Nelson L., Namikawa C., RA Farrington P.F., Ogasawara M., Suzumori K., Tomoda S., Berrebi S., RA Sasaki M., Corvol P., Lifton R.P., Lalouel J.-M.; RT "A molecular variant of angiotensinogen associated with RT preeclampsia."; RL Nat. Genet. 4:59-61(1993). RN [27] RP VARIANTS ILE-242; ARG-244 AND CYS-281. RX PubMed=7607642; DOI=10.1007/BF00214197; RA Hixson J.E., Powers P.K.; RT "Detection and characterization of new mutations in the human RT angiotensinogen gene (AGT)."; RL Hum. Genet. 96:110-112(1995). RN [28] RP VARIANT PHE-43. RX PubMed=7744780; DOI=10.1074/jbc.270.19.11430; RA Inoue I., Rohrwasser A., Helin C., Jeunemaitre X., Crain P., RA Bohlender J., Lifton R.P., Corvol P., Ward K., Lalouel J.-M.; RT "A mutation of angiotensinogen in a patient with preeclampsia leads to RT altered kinetics of the renin-angiotensin system."; RL J. Biol. Chem. 270:11430-11436(1995). RN [29] RP CHARACTERIZATION OF VARIANT CYS-281. RX PubMed=8621667; DOI=10.1074/jbc.271.16.9838; RA Gimenez-Roqueplo A.P., Leconte I., Cohen P., Simon D., Guyene T.T., RA Celerier J., Pau B., Corvol P., Clauser E., Jeunemaitre X.; RT "The natural mutation Y248C of human angiotensinogen leads to abnormal RT glycosylation and altered immunological recognition of the protein."; RL J. Biol. Chem. 271:9838-9844(1996). RN [30] RP VARIANT RTD GLN-375. RX PubMed=16116425; DOI=10.1038/ng1623; RA Gribouval O., Gonzales M., Neuhaus T., Aziza J., Bieth E., Laurent N., RA Bouton J.M., Feuillet F., Makni S., Ben Amar H., Laube G., RA Delezoide A.-L., Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., RA Joubert M., Antignac C., Gubler M.-C.; RT "Mutations in genes in the renin-angiotensin system are associated RT with autosomal recessive renal tubular dysgenesis."; RL Nat. Genet. 37:964-968(2005). CC -!- FUNCTION: Essential component of the renin-angiotensin system CC (RAS), a potent regulator of blood pressure, body fluid and CC electrolyte homeostasis. CC -!- FUNCTION: Angiotensin-2: acts directly on vascular smooth muscle CC as a potent vasoconstrictor, affects cardiac contractility and CC heart rate through its action on the sympathetic nervous system, CC and alters renal sodium and water absorption through its ability CC to stimulate the zona glomerulosa cells of the adrenal cortex to CC synthesize and secrete aldosterone. CC -!- FUNCTION: Angiotensin-3: stimulates aldosterone release. CC -!- FUNCTION: Angiotensin 1-7: is a ligand for the G-protein coupled CC receptor MAS1. Has vasodilator and antidiuretic effects. Has an CC antithrombotic effect that involves MAS1-mediated release of CC nitric oxide from platelets. {ECO:0000250, CC ECO:0000269|PubMed:10619573, ECO:0000269|PubMed:1132082, CC ECO:0000269|PubMed:17138938}. CC -!- SUBUNIT: During pregnancy, exists as a disulfide-linked 2:2 CC heterotetramer with the proform of PRG2 and as a complex (probably CC a 2:2:2 heterohexamer) with pro-PRG2 and C3dg. CC {ECO:0000269|PubMed:20927107, ECO:0000269|PubMed:7539791}. CC -!- INTERACTION: CC P30556:AGTR1; NbExp=2; IntAct=EBI-6622938, EBI-6623016; CC P25095:Agtr1 (xeno); NbExp=10; IntAct=EBI-751728, EBI-764979; CC P50052:AGTR2; NbExp=2; IntAct=EBI-2927577, EBI-1748067; CC Q10714:Ance (xeno); NbExp=2; IntAct=EBI-751728, EBI-115736; CC P00797:REN; NbExp=2; IntAct=EBI-751728, EBI-715794; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma. CC -!- PTM: Beta-decarboxylation of Asp-34 in angiotensin-2, by CC mononuclear leukocytes produces alanine. The resulting peptide CC form, angiotensin-A, has the same affinity for the AT1 receptor as CC angiotensin-2, but a higher affinity for the AT2 receptor. CC {ECO:0000269|PubMed:17138938}. CC -!- PTM: In response to low blood pressure, the enzyme renin/REN CC cleaves angiotensinogen to produce angiotensin-1. Angiotensin-1 is CC a substrate of ACE (angiotensin converting enzyme) that removes a CC dipeptide to yield the physiologically active peptide angiotensin- CC 2. Angiotensin-1 and angiotensin-2 can be further processed to CC generate angiotensin-3, angiotensin-4. Angiotensin 1-9 is cleaved CC from angiotensin-1 by ACE2 and can be further processed by ACE to CC produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4. CC Angiotensin 1-7 has also been proposed to be cleaved from CC angiotensin-2 by ACE2 or from angiotensin-1 by MME (neprilysin). CC {ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:11815627}. CC -!- PTM: The disulfide bond is labile. Angiotensinogen is present in CC the circulation in a near 40:60 ratio with the oxidized disulfide- CC bonded form, which preferentially interacts with receptor-bound CC renin. CC -!- DISEASE: Essential hypertension (EHT) [MIM:145500]: A condition in CC which blood pressure is consistently higher than normal with no CC identifiable cause. {ECO:0000269|PubMed:1394429, CC ECO:0000269|PubMed:8513325}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal CC recessive severe disorder of renal tubular development CC characterized by persistent fetal anuria and perinatal death, CC probably due to pulmonary hypoplasia from early-onset CC oligohydramnios (the Potter phenotype). CC {ECO:0000269|PubMed:16116425}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-10 is the initiator. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and CC polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=AGT"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Angiotensin entry; CC URL="https://en.wikipedia.org/wiki/Angiotensin"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; K02215; AAA51731.1; -; mRNA. DR EMBL; M24689; AAA51679.1; -; Genomic_DNA. DR EMBL; M24686; AAA51679.1; JOINED; Genomic_DNA. DR EMBL; M24687; AAA51679.1; JOINED; Genomic_DNA. DR EMBL; M24688; AAA51679.1; JOINED; Genomic_DNA. DR EMBL; X15324; CAA33385.1; -; Genomic_DNA. DR EMBL; X15325; CAA33385.1; JOINED; Genomic_DNA. DR EMBL; X15326; CAA33385.1; JOINED; Genomic_DNA. DR EMBL; X15327; CAA33385.1; JOINED; Genomic_DNA. DR EMBL; BC011519; AAH11519.1; -; mRNA. DR EMBL; M69110; AAA52282.1; -; mRNA. DR EMBL; S78529; AAD14287.1; -; Genomic_DNA. DR EMBL; S78530; AAD14288.1; -; Genomic_DNA. DR CCDS; CCDS1585.1; -. DR PIR; A35203; ANHU. DR RefSeq; NP_000020.1; NM_000029.3. DR UniGene; Hs.19383; -. DR PDB; 1N9U; NMR; -; A=34-43. DR PDB; 1N9V; NMR; -; A=34-41. DR PDB; 2JP8; NMR; -; P=34-40. DR PDB; 2WXW; X-ray; 3.30 A; A=34-485. DR PDB; 2X0B; X-ray; 4.33 A; B/D/F/H=34-485. DR PDB; 3CK0; X-ray; 3.00 A; P=34-41. DR PDB; 3WOO; X-ray; 1.80 A; C/D=36-41. DR PDB; 3WOR; X-ray; 2.10 A; C/D=34-41. DR PDB; 4AA1; X-ray; 1.99 A; P=34-41. DR PDB; 4APH; X-ray; 1.99 A; P=34-41. DR PDB; 4FYS; X-ray; 2.01 A; C=36-41. DR PDB; 5E2Q; X-ray; 2.40 A; B=34-41. DR PDB; 5M3X; X-ray; 2.63 A; A/B=44-485. DR PDB; 5M3Y; X-ray; 2.30 A; A=34-485. DR PDB; 5XJM; X-ray; 3.20 A; B=35-40. DR PDB; 6I3F; X-ray; 2.55 A; A=34-485. DR PDB; 6I3I; X-ray; 2.97 A; A=34-485. DR PDBsum; 1N9U; -. DR PDBsum; 1N9V; -. DR PDBsum; 2JP8; -. DR PDBsum; 2WXW; -. DR PDBsum; 2X0B; -. DR PDBsum; 3CK0; -. DR PDBsum; 3WOO; -. DR PDBsum; 3WOR; -. DR PDBsum; 4AA1; -. DR PDBsum; 4APH; -. DR PDBsum; 4FYS; -. DR PDBsum; 5E2Q; -. DR PDBsum; 5M3X; -. DR PDBsum; 5M3Y; -. DR PDBsum; 5XJM; -. DR PDBsum; 6I3F; -. DR PDBsum; 6I3I; -. DR ProteinModelPortal; P01019; -. DR SMR; P01019; -. DR BioGrid; 106690; 15. DR CORUM; P01019; -. DR DIP; DIP-309N; -. DR IntAct; P01019; 10. DR MINT; P01019; -. DR STRING; 9606.ENSP00000355627; -. DR ChEMBL; CHEMBL3596085; -. DR DrugBank; DB05206; PS433540. DR MEROPS; I04.953; -. DR CarbonylDB; P01019; -. DR GlyConnect; 703; -. DR iPTMnet; P01019; -. DR PhosphoSitePlus; P01019; -. DR BioMuta; AGT; -. DR DMDM; 113880; -. DR SWISS-2DPAGE; P01019; -. DR EPD; P01019; -. DR jPOST; P01019; -. DR MaxQB; P01019; -. DR PaxDb; P01019; -. DR PeptideAtlas; P01019; -. DR PRIDE; P01019; -. DR ProteomicsDB; 51306; -. DR DNASU; 183; -. DR Ensembl; ENST00000366667; ENSP00000355627; ENSG00000135744. DR GeneID; 183; -. DR KEGG; hsa:183; -. DR UCSC; uc001hty.6; human. DR CTD; 183; -. DR DisGeNET; 183; -. DR EuPathDB; HostDB:ENSG00000135744.7; -. DR GeneCards; AGT; -. DR HGNC; HGNC:333; AGT. DR HPA; CAB025798; -. DR HPA; HPA001557; -. DR MalaCards; AGT; -. DR MIM; 106150; gene. DR MIM; 145500; phenotype. DR MIM; 267430; phenotype. DR neXtProt; NX_P01019; -. DR OpenTargets; ENSG00000135744; -. DR Orphanet; 243761; NON RARE IN EUROPE: Essential hypertension. DR Orphanet; 97369; Renal tubular dysgenesis of genetic origin. DR PharmGKB; PA42; -. DR eggNOG; KOG2392; Eukaryota. DR eggNOG; COG4826; LUCA. DR GeneTree; ENSGT00890000139531; -. DR HOVERGEN; HBG004233; -. DR InParanoid; P01019; -. DR KO; K09821; -. DR OMA; TYVHFQG; -. DR OrthoDB; 450590at2759; -. DR PhylomeDB; P01019; -. DR TreeFam; TF343201; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SIGNOR; P01019; -. DR ChiTaRS; AGT; human. DR EvolutionaryTrace; P01019; -. DR GeneWiki; Angiotensin; -. DR GenomeRNAi; 183; -. DR PMAP-CutDB; P01019; -. DR PRO; PR:P01019; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000135744; Expressed in 211 organ(s), highest expression level in liver. DR ExpressionAtlas; P01019; baseline and differential. DR Genevisible; P01019; HS. DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; TAS:BHF-UCL. DR GO; GO:0005179; F:hormone activity; ISS:BHF-UCL. DR GO; GO:0048018; F:receptor ligand activity; IDA:BHF-UCL. DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central. DR GO; GO:0017080; F:sodium channel regulator activity; IMP:BHF-UCL. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; TAS:BHF-UCL. DR GO; GO:0031702; F:type 1 angiotensin receptor binding; IPI:BHF-UCL. DR GO; GO:0031703; F:type 2 angiotensin receptor binding; IPI:BHF-UCL. DR GO; GO:0007202; P:activation of phospholipase C activity; IEA:Ensembl. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0038166; P:angiotensin-activated signaling pathway; IDA:BHF-UCL. DR GO; GO:0003051; P:angiotensin-mediated drinking behavior; IEA:Ensembl. DR GO; GO:0014824; P:artery smooth muscle contraction; IEA:Ensembl. DR GO; GO:0008306; P:associative learning; IEA:Ensembl. DR GO; GO:0001974; P:blood vessel remodeling; TAS:BHF-UCL. DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:1904385; P:cellular response to angiotensin; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0006883; P:cellular sodium ion homeostasis; IEA:Ensembl. DR GO; GO:0050663; P:cytokine secretion; IEA:Ensembl. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0007199; P:G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger; TAS:BHF-UCL. DR GO; GO:0001822; P:kidney development; IMP:BHF-UCL. DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; NAS:BHF-UCL. DR GO; GO:0016525; P:negative regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl. DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0051387; P:negative regulation of neurotrophin TRK receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; TAS:BHF-UCL. DR GO; GO:0034104; P:negative regulation of tissue remodeling; IEA:Ensembl. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; TAS:BHF-UCL. DR GO; GO:0035106; P:operant conditioning; IEA:Ensembl. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; NAS:BHF-UCL. DR GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; IMP:UniProtKB. DR GO; GO:0045777; P:positive regulation of blood pressure; IEA:Ensembl. DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; IDA:UniProtKB. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:BHF-UCL. DR GO; GO:0032270; P:positive regulation of cellular protein metabolic process; IDA:BHF-UCL. DR GO; GO:0010873; P:positive regulation of cholesterol esterification; IDA:BHF-UCL. DR GO; GO:0001819; P:positive regulation of cytokine production; TAS:BHF-UCL. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; IEA:Ensembl. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:BHF-UCL. DR GO; GO:1903598; P:positive regulation of gap junction assembly; IGI:BHF-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; TAS:BHF-UCL. DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IEA:Ensembl. DR GO; GO:1905589; P:positive regulation of L-arginine import across plasma membrane; IEA:Ensembl. DR GO; GO:1905010; P:positive regulation of L-lysine import across plasma membrane; IEA:Ensembl. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IC:BHF-UCL. DR GO; GO:1902632; P:positive regulation of membrane hyperpolarization; IMP:BHF-UCL. DR GO; GO:0033864; P:positive regulation of NAD(P)H oxidase activity; TAS:BHF-UCL. DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL. DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL. DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; TAS:BHF-UCL. DR GO; GO:0035815; P:positive regulation of renal sodium excretion; IEA:Ensembl. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IEA:Ensembl. DR GO; GO:1904707; P:positive regulation of vascular smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl. DR GO; GO:0008217; P:regulation of blood pressure; IGI:BHF-UCL. DR GO; GO:0002034; P:regulation of blood vessel diameter by renin-angiotensin; TAS:BHF-UCL. DR GO; GO:0002016; P:regulation of blood volume by renin-angiotensin; NAS:BHF-UCL. DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl. DR GO; GO:1903779; P:regulation of cardiac conduction; IGI:BHF-UCL. DR GO; GO:0001558; P:regulation of cell growth; NAS:BHF-UCL. DR GO; GO:0042127; P:regulation of cell population proliferation; NAS:BHF-UCL. DR GO; GO:1901201; P:regulation of extracellular matrix assembly; IGI:BHF-UCL. DR GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl. DR GO; GO:0019216; P:regulation of lipid metabolic process; TAS:Reactome. DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:0014061; P:regulation of norepinephrine secretion; IEA:Ensembl. DR GO; GO:0002019; P:regulation of renal output by angiotensin; NAS:BHF-UCL. DR GO; GO:0035813; P:regulation of renal sodium excretion; NAS:BHF-UCL. DR GO; GO:0051969; P:regulation of transmission of nerve impulse; IEA:Ensembl. DR GO; GO:0019229; P:regulation of vasoconstriction; NAS:BHF-UCL. DR GO; GO:0003014; P:renal system process; IDA:UniProtKB. DR GO; GO:0002018; P:renin-angiotensin regulation of aldosterone production; NAS:BHF-UCL. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0014873; P:response to muscle activity involved in regulation of muscle adaptation; ISS:BHF-UCL. DR GO; GO:0048659; P:smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0051403; P:stress-activated MAPK cascade; IEA:Ensembl. DR GO; GO:0070471; P:uterine smooth muscle contraction; IEA:Ensembl. DR GO; GO:0042311; P:vasodilation; IEA:Ensembl. DR CDD; cd02054; angiotensinogen; 1. DR InterPro; IPR000227; Angiotensinogen. DR InterPro; IPR033834; Angiotensinogen_serpin. DR InterPro; IPR023795; Serpin_CS. DR InterPro; IPR023796; Serpin_dom. DR InterPro; IPR000215; Serpin_fam. DR InterPro; IPR036186; Serpin_sf. DR PANTHER; PTHR11461; PTHR11461; 1. DR PANTHER; PTHR11461:SF13; PTHR11461:SF13; 1. DR Pfam; PF00079; Serpin; 1. DR PRINTS; PR00654; ANGIOTENSNGN. DR SMART; SM00093; SERPIN; 1. DR SUPFAM; SSF56574; SSF56574; 1. DR PROSITE; PS00284; SERPIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Disease mutation; Disulfide bond; Glycoprotein; Polymorphism; KW Reference proteome; Secreted; Signal; Vasoactive; Vasoconstrictor. FT SIGNAL 1 33 {ECO:0000269|PubMed:4300938, FT ECO:0000269|PubMed:7259779, FT ECO:0000269|PubMed:7539791}. FT CHAIN 34 485 Angiotensinogen. FT /FTId=PRO_0000032456. FT PEPTIDE 34 43 Angiotensin-1. FT /FTId=PRO_0000032457. FT PEPTIDE 34 42 Angiotensin 1-9. FT /FTId=PRO_0000420659. FT PEPTIDE 34 41 Angiotensin-2. FT /FTId=PRO_0000032458. FT PEPTIDE 34 40 Angiotensin 1-7. FT /FTId=PRO_0000420660. FT PEPTIDE 34 38 Angiotensin 1-5. FT /FTId=PRO_0000420661. FT PEPTIDE 34 37 Angiotensin 1-4. FT /FTId=PRO_0000420662. FT PEPTIDE 35 41 Angiotensin-3. FT /FTId=PRO_0000032459. FT PEPTIDE 36 41 Angiotensin-4. FT /FTId=PRO_0000420663. FT MOD_RES 34 34 Beta-decarboxylated aspartate; in form FT angiotensin-A. FT {ECO:0000269|PubMed:17138938}. FT CARBOHYD 47 47 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:3934016}. FT CARBOHYD 170 170 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:3934016}. FT CARBOHYD 304 304 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:3934016}. FT CARBOHYD 328 328 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:3934016}. FT DISULFID 51 171 {ECO:0000269|PubMed:20927107}. FT VARIANT 43 43 L -> F (associated with susceptibility to FT pre-eclampsia; alters the reactions with FT renin and angiotensin-converting enzyme; FT dbSNP:rs41271499). FT {ECO:0000269|PubMed:7744780}. FT /FTId=VAR_022933. FT VARIANT 98 98 E -> K (in dbSNP:rs11568032). FT /FTId=VAR_029166. FT VARIANT 114 114 G -> C (in dbSNP:rs2229389). FT /FTId=VAR_051939. FT VARIANT 137 137 T -> M (in dbSNP:rs34829218). FT /FTId=VAR_035431. FT VARIANT 207 207 T -> M (associated with hypertension; FT dbSNP:rs4762). FT {ECO:0000269|PubMed:1394429}. FT /FTId=VAR_007093. FT VARIANT 242 242 T -> I (associated with susceptibility to FT hypertension; dbSNP:rs765678426). FT {ECO:0000269|PubMed:7607642}. FT /FTId=VAR_007094. FT VARIANT 244 244 L -> R (associated with susceptibility to FT hypertension; dbSNP:rs5041). FT {ECO:0000269|PubMed:7607642}. FT /FTId=VAR_007095. FT VARIANT 268 268 M -> I (in dbSNP:rs11568053). FT /FTId=VAR_029167. FT VARIANT 268 268 M -> T (associated with essential FT hypertension and pre-eclampsia; FT dbSNP:rs699). FT {ECO:0000269|PubMed:1394429, FT ECO:0000269|PubMed:8513325}. FT /FTId=VAR_007096. FT VARIANT 281 281 Y -> C (associated with susceptibility to FT hypertension; alters the structure, FT glycosylation and secretion of FT angiotensinogen; dbSNP:rs56073403). FT {ECO:0000269|PubMed:1394429, FT ECO:0000269|PubMed:7607642, FT ECO:0000269|PubMed:8621667}. FT /FTId=VAR_007097. FT VARIANT 335 335 P -> S (in dbSNP:rs17856352). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_035432. FT VARIANT 375 375 R -> Q (in RTD; dbSNP:rs74315283). FT {ECO:0000269|PubMed:16116425}. FT /FTId=VAR_035433. FT VARIANT 392 392 L -> M (in dbSNP:rs1805090). FT /FTId=VAR_014573. FT CONFLICT 51 51 C -> S (in Ref. 7; AA sequence). FT {ECO:0000305}. FT CONFLICT 58 58 N -> D (in Ref. 7; AA sequence). FT {ECO:0000305}. FT CONFLICT 333 333 Q -> E (in Ref. 2; AAA51679). FT {ECO:0000305}. FT TURN 42 44 {ECO:0000244|PDB:2WXW}. FT TURN 48 50 {ECO:0000244|PDB:5M3Y}. FT STRAND 59 62 {ECO:0000244|PDB:2WXW}. FT HELIX 81 93 {ECO:0000244|PDB:5M3Y}. FT HELIX 97 119 {ECO:0000244|PDB:5M3Y}. FT STRAND 122 124 {ECO:0000244|PDB:5M3Y}. FT TURN 125 127 {ECO:0000244|PDB:5M3Y}. FT STRAND 128 131 {ECO:0000244|PDB:5M3Y}. FT HELIX 136 148 {ECO:0000244|PDB:5M3Y}. FT HELIX 152 162 {ECO:0000244|PDB:5M3Y}. FT STRAND 167 169 {ECO:0000244|PDB:5M3Y}. FT TURN 171 173 {ECO:0000244|PDB:2WXW}. FT HELIX 177 192 {ECO:0000244|PDB:5M3Y}. FT TURN 195 197 {ECO:0000244|PDB:2WXW}. FT STRAND 203 213 {ECO:0000244|PDB:5M3Y}. FT HELIX 221 230 {ECO:0000244|PDB:5M3Y}. FT STRAND 234 238 {ECO:0000244|PDB:5M3Y}. FT HELIX 244 259 {ECO:0000244|PDB:5M3Y}. FT STRAND 276 287 {ECO:0000244|PDB:5M3Y}. FT STRAND 291 293 {ECO:0000244|PDB:5M3Y}. FT STRAND 298 300 {ECO:0000244|PDB:5M3Y}. FT STRAND 302 305 {ECO:0000244|PDB:5M3Y}. FT STRAND 308 310 {ECO:0000244|PDB:5M3Y}. FT STRAND 312 324 {ECO:0000244|PDB:5M3Y}. FT TURN 325 328 {ECO:0000244|PDB:5M3Y}. FT STRAND 329 349 {ECO:0000244|PDB:5M3Y}. FT HELIX 350 352 {ECO:0000244|PDB:5M3Y}. FT HELIX 353 360 {ECO:0000244|PDB:5M3Y}. FT HELIX 363 369 {ECO:0000244|PDB:5M3Y}. FT STRAND 373 382 {ECO:0000244|PDB:5M3Y}. FT STRAND 385 391 {ECO:0000244|PDB:5M3Y}. FT HELIX 392 395 {ECO:0000244|PDB:5M3Y}. FT TURN 396 400 {ECO:0000244|PDB:5M3Y}. FT HELIX 401 404 {ECO:0000244|PDB:5M3Y}. FT STRAND 407 409 {ECO:0000244|PDB:2WXW}. FT TURN 412 414 {ECO:0000244|PDB:5M3Y}. FT STRAND 421 433 {ECO:0000244|PDB:5M3Y}. FT STRAND 452 455 {ECO:0000244|PDB:5M3Y}. FT STRAND 460 466 {ECO:0000244|PDB:5M3Y}. FT TURN 467 470 {ECO:0000244|PDB:5M3Y}. FT STRAND 471 479 {ECO:0000244|PDB:5M3Y}. SQ SEQUENCE 485 AA; 53154 MW; 5026C2DFB2DD236E CRC64; MRKRAPQSEM APAGVSLRAT ILCLLAWAGL AAGDRVYIHP FHLVIHNEST CEQLAKANAG KPKDPTFIPA PIQAKTSPVD EKALQDQLVL VAAKLDTEDK LRAAMVGMLA NFLGFRIYGM HSELWGVVHG ATVLSPTAVF GTLASLYLGA LDHTADRLQA ILGVPWKDKN CTSRLDAHKV LSALQAVQGL LVAQGRADSQ AQLLLSTVVG VFTAPGLHLK QPFVQGLALY TPVVLPRSLD FTELDVAAEK IDRFMQAVTG WKTGCSLMGA SVDSTLAFNT YVHFQGKMKG FSLLAEPQEF WVDNSTSVSV PMLSGMGTFQ HWSDIQDNFS VTQVPFTESA CLLLIQPHYA SDLDKVEGLT FQQNSLNWMK KLSPRTIHLT MPQLVLQGSY DLQDLLAQAE LPAILHTELN LQKLSNDRIR VGEVLNSIFF ELEADEREPT ESTQQLNKPE VLEVTLNRPF LFAVYDQSAT ALHFLGRVAN PLSTA //