Reviewed, UniProtKB/Swiss-Prot P01019 (ANGT_HUMAN)

Names and origin

Protein names

Recommended name:
    Angiotensinogen
Alternative name(s):
    Serpin A8
Cleaved into the following 3 chains:
    1- Recommended name:
            Angiotensin-1
        Alternative name(s):
            Angiotensin I
              Short name=Ang I
    2- Recommended name:
            Angiotensin-2
        Alternative name(s):
            Angiotensin II
              Short name=Ang II
    3- Recommended name:
            Angiotensin-3
        Alternative name(s):
            Angiotensin III
              Short name=Ang III
            Des-Asp[1]-angiotensin II

Gene names

Name:	AGT
Synonyms:	SERPINA8

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	485 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	In response to lowered blood pressure, the enzyme renin cleaves angiotensin-1, from angiotensinogen. ACE (angiotensin converting enzyme) then removes a dipeptide to yield the physiologically active peptide angiotensin-2, the most potent pressor substance known, which helps regulate volume and mineral balance of body fluids. Angiotensin-3 stimulates aldosterone release.
Subunit structure	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.
Post-translational modification	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.
Involvement in disease	Defects in AGT are associated with susceptibility to essential hypertension [MIM:145500]. Hypertension also occurs in 5-7% of all pregnancies where it is a leading cause of maternal, fetal and neonatal morbidity and mortality. Among pregnancy-induced hypertension cases, severe pre-eclampsia [MIM:189800] is characterized by the development of hypertension and proteinuria after the 20th week of pregnancy and is the most distinctive, life-threatening form. 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).
Sequence similarities	Belongs to the serpin family.
Caution	It is uncertain whether Met-1 or Met-10 is the initiator.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Vasoactive Vasoconstrictor
PTM	Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to IP3 second messenger (phospholipase C activating) Non-traceable author statement. Source: UniProtKB G-protein signaling, coupled to cGMP nucleotide second messenger Traceable author statement. Source: UniProtKB blood vessel remodeling Traceable author statement. Source: UniProtKB cell-cell signaling Ref.16 Traceable author statement. Source: ProtInc negative regulation of nerve growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB nitric oxide mediated signal transduction Traceable author statement. Source: UniProtKB oxygen and reactive oxygen species metabolic process Traceable author statement. Source: UniProtKB positive regulation of NAD(P)H oxidase activity Traceable author statement. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Traceable author statement. Source: UniProtKB positive regulation of apoptosis Inferred from direct assay. Source: UniProtKB positive regulation of cardiac muscle hypertrophy Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cytokine production Traceable author statement. Source: UniProtKB positive regulation of endothelial cell migration Inferred from direct assay. Source: UniProtKB positive regulation of epidermal growth factor receptor signaling pathway Inferred from direct assay. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of inflammatory response Traceable author statement. Source: UniProtKB positive regulation of peptidyl-tyrosine phosphorylation Inferred from direct assay. Source: UniProtKB positive regulation of phosphoinositide 3-kinase cascade Inferred from direct assay. Source: UniProtKB regulation of cell growth Non-traceable author statement. Source: UniProtKB regulation of natriuresis Non-traceable author statement. Source: UniProtKB regulation of renal output by angiotensin Non-traceable author statement. Source: UniProtKB regulation of vasoconstriction Non-traceable author statement. Source: UniProtKB renin-angiotensin regulation of aldosterone production Non-traceable author statement. Source: UniProtKB response to muscle activity involved in regulation of muscle adaptation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HPA extracellular space Inferred by curator. Source: UniProtKB soluble fraction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	growth factor activity Traceable author statement. Source: UniProtKB hormone activity Inferred by curator. Source: UniProtKB serine-type endopeptidase inhibitor activity Traceable author statement. Source: ProtInc type 1 angiotensin receptor binding Inferred from physical interaction. Source: UniProtKB type 2 angiotensin receptor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 33	33
	Chain	34 – 485	452	Angiotensinogen		PRO_0000032456
	Peptide	34 – 43	10	Angiotensin-1		PRO_0000032457
	Peptide	34 – 41	8	Angiotensin-2		PRO_0000032458
	Peptide	35 – 41	7	Angiotensin-3		PRO_0000032459
Amino acid modifications
	Modified residue	34	1	Beta-decarboxylated aspartate; in form angiotensin-A
	Glycosylation	47	1	N-linked (GlcNAc...)
	Glycosylation	170	1	N-linked (GlcNAc...)
	Glycosylation	304	1	N-linked (GlcNAc...)
	Glycosylation	328	1	N-linked (GlcNAc...)
Natural variations
	Natural variant	43	1	L → F in pre-eclampsia; alters the reactions with renin and angiotensin-converting enzyme. dbSNP rs41271499.		VAR_022933
	Natural variant	98	1	E → K: dbSNP rs11568032.		VAR_029166
	Natural variant	137	1	T → M: dbSNP rs34829218.		VAR_035431
	Natural variant	207	1	T → M Associated with hypertension. dbSNP rs4762.		VAR_007093
	Natural variant	242	1	T → I in hypertension.		VAR_007094
	Natural variant	244	1	L → R in hypertension. dbSNP rs5041.		VAR_007095
	Natural variant	268	1	M → I: dbSNP rs11568053.		VAR_029167
	Natural variant	268	1	M → T Associated with essential hypertension and pre-eclampsia. dbSNP rs699.		VAR_007096
	Natural variant	281	1	Y → C in hypertension; alters the structure, glycosylation and secretion of angiotensinogen.		VAR_007097
	Natural variant	335	1	P → S: dbSNP rs17856352.		VAR_035432
	Natural variant	375	1	R → Q in RTD.		VAR_035433
	Natural variant	392	1	L → M: dbSNP rs1805090.		VAR_014573
Experimental info
	Sequence conflict	51	1	C → S AA sequence Ref.7
	Sequence conflict	58	1	N → D AA sequence Ref.7
	Sequence conflict	333	1	Q → E in AAA51679. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P01019-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 5026C2DFB2DD236E	FASTA	485	53,154
	10 20 30 40 50 60 MRKRAPQSEM APAGVSLRAT ILCLLAWAGL AAGDRVYIHP FHLVIHNEST CEQLAKANAG 70 80 90 100 110 120 KPKDPTFIPA PIQAKTSPVD EKALQDQLVL VAAKLDTEDK LRAAMVGMLA NFLGFRIYGM 130 140 150 160 170 180 HSELWGVVHG ATVLSPTAVF GTLASLYLGA LDHTADRLQA ILGVPWKDKN CTSRLDAHKV 190 200 210 220 230 240 LSALQAVQGL LVAQGRADSQ AQLLLSTVVG VFTAPGLHLK QPFVQGLALY TPVVLPRSLD 250 260 270 280 290 300 FTELDVAAEK IDRFMQAVTG WKTGCSLMGA SVDSTLAFNT YVHFQGKMKG FSLLAEPQEF 310 320 330 340 350 360 WVDNSTSVSV PMLSGMGTFQ HWSDIQDNFS VTQVPFTESA CLLLIQPHYA SDLDKVEGLT 370 380 390 400 410 420 FQQNSLNWMK KLSPRTIHLT MPQLVLQGSY DLQDLLAQAE LPAILHTELN LQKLSNDRIR 430 440 450 460 470 480 VGEVLNSIFF ELEADEREPT ESTQQLNKPE VLEVTLNRPF LFAVYDQSAT ALHFLGRVAN PLSTA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence." Kageyama R., Ohkubo H., Nakanishi S. Biochemistry 23:3603-3609(1984) [PubMed: 6089875] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Structure of human angiotensinogen gene." Gaillard I., Clauser E., Corvol P. DNA 8:87-99(1989) [PubMed: 2924688] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter." Fukamizu A., Takahashi S., Seo M.S., Tada M., Tanimoto K., Uehara S., Murakami K. J. Biol. Chem. 265:7576-7582(1990) [PubMed: 1692023] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-335. Tissue: Brain.
[5]	"Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in rat heart." Kunapuli S.P., Kumar A. Circ. Res. 60:786-790(1987) [PubMed: 2885106] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-338.
[6]	"Tissue specific hormonal regulation of the rat angiotensinogen gene expression." Kunapuli S.P., Benedict C.R., Kumar A. Arch. Biochem. Biophys. 254:642-646(1987) [PubMed: 3579322] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-184.
[7]	"The amino terminal amino acid sequence of human angiotensinogen." Tewksbury D.A., Dart R.A., Travis J. Biochem. Biophys. Res. Commun. 99:1311-1315(1981) [PubMed: 7259779] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-58.
[8]	"Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma." Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., Stigbrand T., Gleich G.J., Sottrup-Jensen L. J. Biol. Chem. 270:13645-13651(1995) [PubMed: 7539791] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-45, SUBUNIT. Tissue: Serum.
[9]	"Enzymatic degradation and electrophoresis of human angiotensin I." Arakawa K., Minohara A., Yamada J., Nakamura M. Biochim. Biophys. Acta 168:106-112(1968) [PubMed: 4300938] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-43.
[10]	"Processing of rat and human angiotensinogen precursors by microsomal membranes." Campbell D.J., Bouhnik J., Coezy E., Menard J., Corvol P. Mol. Cell. Endocrinol. 43:31-40(1985) [PubMed: 3934016] [Abstract] Cited for: GLYCOSYLATION AT ASN-47; ASN-170; ASN-304 AND ASN-328.
[11]	"Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system." Goodfriend T.L., Peach M.J. Circ. Res. 36:38-48(1975) [PubMed: 1132082] [Abstract] Cited for: FUNCTION OF ANGIOTENSIN-3.
[12]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-47, MASS SPECTROMETRY. Tissue: Plasma.
[13]	"Mass-spectrometric identification of a novel angiotensin peptide in human plasma." Jankowski V., Vanholder R., van der Giet M., Tolle M., Karadogan S., Gobom J., Furkert J., Oksche A., Krause E., Tran T.N., Tepel M., Schuchardt M., Schluter H., Wiedon A., Beyermann M., Bader M., Todiras M., Zidek W., Jankowski J. Arterioscler. Thromb. Vasc. Biol. 27:297-302(2007) [PubMed: 17138938] [Abstract] Cited for: DECARBOXYLATION AT ASP-34, FUNCTION, MASS SPECTROMETRY.
[14]	"The octapeptide angiotensin II adopts a well-defined structure in a phospholipid environment." Carpenter K.A., Wilkes B.C., Schiller P.W. Eur. J. Biochem. 251:448-453(1998) [PubMed: 9492317] [Abstract] Cited for: STRUCTURE BY NMR OF ANGIOTENSIN-2.
[15]	"Molecular basis of human hypertension: role of angiotensinogen." Jeunemaitre X., Soubrier F., Kotelevtsev Y.V., Lifton R.P., Williams C.S., Charru A., Hunt S.C., Hopkins P.N., Williams R.R., Lalouel J.-M., Corvol P. Cell 71:169-180(1992) [PubMed: 1394429] [Abstract] Cited for: VARIANTS MET-207; THR-268 AND CYS-281.
[16]	"A molecular variant of angiotensinogen associated with preeclampsia." Ward K., Hata A., Jeunemaitre X., Helin C., Nelson L., Namikawa C., Farrington P.F., Ogasawara M., Suzumori K., Tomoda S., Berrebi S., Sasaki M., Corvol P., Lifton R.P., Lalouel J.-M. Nat. Genet. 4:59-61(1993) [PubMed: 8513325] [Abstract] Cited for: VARIANT THR-268.
[17]	"Detection and characterization of new mutations in the human angiotensinogen gene (AGT)." Hixson J.E., Powers P.K. Hum. Genet. 96:110-112(1995) [PubMed: 7607642] [Abstract] Cited for: VARIANTS ILE-242; ARG-244 AND CYS-281.
[18]	"A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system." Inoue I., Rohrwasser A., Helin C., Jeunemaitre X., Crain P., Bohlender J., Lifton R.P., Corvol P., Ward K., Lalouel J.-M. J. Biol. Chem. 270:11430-11436(1995) [PubMed: 7744780] [Abstract] Cited for: VARIANT PRE-ECLAMPSIA PHE-43.
[19]	"The natural mutation Y248C of human angiotensinogen leads to abnormal glycosylation and altered immunological recognition of the protein." Gimenez-Roqueplo A.P., Leconte I., Cohen P., Simon D., Guyene T.T., Celerier J., Pau B., Corvol P., Clauser E., Jeunemaitre X. J. Biol. Chem. 271:9838-9844(1996) [PubMed: 8621667] [Abstract] Cited for: CHARACTERIZATION OF VARIANT CYS-281.
[20]	"Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis." Gribouval O., Gonzales M., Neuhaus T., Aziza J., Bieth E., Laurent N., Bouton J.M., Feuillet F., Makni S., Ben Amar H., Laube G., Delezoide A.-L., Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., Joubert M., Antignac C., Gubler M.-C. Nat. Genet. 37:964-968(2005) [PubMed: 16116425] [Abstract] Cited for: VARIANT RTD GLN-375.
+	Additional computationally mapped references.

Web resources

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Angiotensin entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

ANHU. A35203.

RefSeq

NP_000020.1.

UniGene

Hs.19383

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N9U	NMR	-	A	34-43	[»]
1N9V	NMR	-	A	34-41	[»]
2JP8	NMR	-	P	34-40	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:309N.

IntAct

P01019.

Protein family/group databases

MEROPS

I04.953.

2-D gel databases

SWISS-2DPAGE

P01019.

Proteomic databases

PeptideAtlas

P01019.

Genome annotation databases

Ensembl

ENSG00000135744. Homo sapiens. [Contig view]

GeneID

183.

KEGG

hsa:183.

Organism-specific databases

H-InvDB

HIX0001686.

HGNC

HGNC:333. AGT.

HPA

HPA001557.

MIM

106150. gene.
145500. phenotype.
267430. phenotype.

Orphanet

3033. Renal tubular dysgenesis.

PharmGKB

PA42.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P01019.

Gene expression databases

ArrayExpress

P01019.

CleanEx

HS_AGT.

GermOnline

ENSG00000135744. Homo sapiens.

Family and domain databases

InterPro

IPR000227. Angiotensngn.
IPR000215. Protease_inhib_I4_serpin.
[Graphical view]

PANTHER

PTHR11461. Prot_inh_serpin. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

PRINTS

PR00654. ANGIOTENSNGN.

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01258. Aliskiren.
DB01076. Atorvastatin.
DB01340. Cilazapril.
DB01029. Irbesartan.
DB00722. Lisinopril.
DB01092. Ouabain.
DB00641. Simvastatin.

NextBio

748.

SOURCE

Search...

Entry information

Entry name

ANGT_HUMAN

Accession

Primary (citable) accession number: P01019
Secondary accession number(s): Q16358, Q16359, Q96F91

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	November 25, 2008
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)