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UniProtKB/Swiss-Prot entry P00797


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name RENI_HUMAN
Primary accession number P00797
Secondary accession number Q6T5C2
Integrated into Swiss-Prot on July 21, 1986
Sequence was last modified on January 1, 1988 (Sequence version 1)
Annotations were last modified on    April 29, 2008 (Entry version 110)
Name and origin of the protein
Protein name Renin [Precursor]
Synonyms EC 3.4.23.15
Angiotensinogenase
Gene name
Name: REN
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
PubMed=6324167 [NCBI, ExPASy, EBI, Israel, Japan]
Imai T., Miyazaki H., Hirose S., Hori H., Hayashi T., Kageyama R., Ohkubo H., Nakanishi S., Murakami K.;
"Cloning and sequence analysis of cDNA for human renin precursor.";
Proc. Natl. Acad. Sci. U.S.A. 80:7405-7409(1983).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
PubMed=3530608 [NCBI, ExPASy, EBI, Israel, Japan]
Morris B.J.;
"New possibilities for intracellular renin and inactive renin now that the structure of the human renin gene has been elucidated.";
Clin. Sci. 71:345-355(1986).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Fetal liver;
PubMed=6391881 [NCBI, ExPASy, EBI, Israel, Japan]
Hardman J.A., Hort Y.J., Catanzaro D.F., Tellam J.T., Baxter J.D., Morris B.J., Shine J.;
"Primary structure of the human renin gene.";
DNA 3:457-468(1984).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D., Toth E.J., Krauss R.M., Nickerson D.A.;
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature04727; PubMed=16710414 [NCBI, ExPASy, EBI, Israel, Japan]
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Colon, and Ovary;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 108-406 (ISOFORM 1).
DOI=10.1093/nar/11.20.7181; PubMed=6138751 [NCBI, ExPASy, EBI, Israel, Japan]
Soubrier F., Panthier J.-J., Corvol P., Rougeon F.;
"Molecular cloning and nucleotide sequence of a human renin cDNA fragment.";
Nucleic Acids Res. 11:7181-7190(1983).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
DOI=10.1016/0378-1119(86)90393-8; PubMed=3032746 [NCBI, ExPASy, EBI, Israel, Japan]
Fukamizu A., Nishi K., Nishimatsu S., Miyazaki H., Hirose S., Murakami K.;
"Human renin gene of renin-secreting tumor.";
Gene 49:139-145(1986).
[9]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
PubMed=2540188 [NCBI, ExPASy, EBI, Israel, Japan]
Burt D.W., Nakamura N., Kelley P., Dzau V.J.;
"Identification of negative and positive regulatory elements in the human renin gene.";
J. Biol. Chem. 264:7357-7362(1989).
[10]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
DOI=10.1016/0378-1119(86)90270-2; PubMed=3516796 [NCBI, ExPASy, EBI, Israel, Japan]
Soubrier F., Panthier J.J., Houot A.-M., Rougeon F., Corvol P.;
"Segmental homology between the promoter region of the human renin gene and the mouse ren1 and ren2 promoter regions.";
Gene 41:85-92(1986).
[11]
PARTIAL PROTEIN SEQUENCE OF 24-42 AND 67-86.
PubMed=2016271 [NCBI, ExPASy, EBI, Israel, Japan]
Ishizuka Y., Shoda A., Yoshida S., Kawamura Y., Haraguchi K., Murakami K.;
"Isolation and characterization of recombinant human prorenin in Chinese hamster ovary cells.";
J. Biochem. 109:30-35(1991).
[12]
INTERACTION WITH ATP6AP2, AND CHARACTERIZATION.
PubMed=12045255 [NCBI, ExPASy, EBI, Israel, Japan]
Nguyen G., Delarue F., Burckle C., Bouzhir L., Giller T., Sraer J.-D.;
"Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin.";
J. Clin. Invest. 109:1417-1427(2002).
[13]
X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
PubMed=2493678 [NCBI, ExPASy, EBI, Israel, Japan]
Sielecki A.R., Hayakawa K., Fujinaga M., Murphy M.E.P., Fraser M., Muir A.K., Carilli C.T., Lewicki J.A., Baxter J.D., James M.N.G.;
"Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5-A resolution.";
Science 243:1346-1351(1989).
[14]
X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
DOI=10.1038/357466a0; PubMed=1608447 [NCBI, ExPASy, EBI, Israel, Japan]
Dhanaraj V., Dealwis C.G., Frazao C., Badasso M., Sibanda B.L., Tickle I.J., Cooper J.B., Driessen H.P.C., Newman M., Aguilar C., Wood S.P., Blundell T.L., Hobart P.M., Geoghegan K.F., Ammirati M.J., Danley D.E., O'Connor B.A., Hoover D.J.;
"X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins.";
Nature 357:466-472(1992).
[15]
VARIANTS RTD ASN-104 AND LYS-230.
DOI=10.1038/ng1623; PubMed=16116425 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis.";
Nat. Genet. 37:964-968(2005).
Comments
  • FUNCTION: Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
  • CATALYTIC ACTIVITY: Cleavage of Leu-|-Xaa bond in angiotensinogen to generate angiotensin I.
  • ENZYME REGULATION: Interaction with ATP6AP2 results in a 5-fold increased efficiency in angiotensinogen processing.
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=1 µM for angiotensinogen (in absence of ATP6AP2);
    KM=0.15 µM for angiotensinogen (in presence of membrane-bound ATP6AP2);
  • SUBUNIT: Interacts with ATP6AP2.
  • SUBCELLULAR LOCATION: Secreted. Membrane. Note=Associated to membranes via binding to ATP6AP2.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP00797-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP00797-2
    Features which should be applied to build the isoform sequence: VSP_012899.
  • DISEASE: Defects in REN 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 peptidase A1 family [view classification].
  • WEB RESOURCE: Name=Wikipedia; Note=Renin entry; URL="http://en.wikipedia.org/wiki/Renin";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
L00073; AAA60363.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00064; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00065; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00066; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00067; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00068; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00069; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00070; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00071; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L00072; AAA60363.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26901; AAA60364.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26899; AAA60364.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26900; AAA60364.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10152; AAD03461.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10030; AAD03461.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10128; AAD03461.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10150; AAD03461.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10151; AAD03461.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY436324; AAR03502.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL592114; CAH71224.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL592146; CAH71224.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL592146; CAI16594.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AL592114; CAI16594.1; JOINED; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC033474; AAH33474.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC047752; AAH47752.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M15410; AAA60263.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M26440; AAA60365.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M13253; AAA60262.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A21454; REHUK.
RefSeq NP_000528.1; -.
UniGene Hs.3210
3D structure databases
PDB
1BBS; X-ray; 2.80 A; A/B=67-406.[ExPASy / RCSB / EBI]
1BIL; X-ray; 2.40 A; A/B=70-406.[ExPASy / RCSB / EBI]
1BIM; X-ray; 2.80 A; A/B=70-406.[ExPASy / RCSB / EBI]
1HRN; X-ray; 1.80 A; A/B=70-406.[ExPASy / RCSB / EBI]
1RNE; X-ray; 2.40 A; A=67-406.[ExPASy / RCSB / EBI]
2BKS; X-ray; 2.20 A; A/B=67-406.[ExPASy / RCSB / EBI]
2BKT; X-ray; 2.30 A; A/B=67-406.[ExPASy / RCSB / EBI]
2FS4; X-ray; 2.20 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G1N; X-ray; 2.90 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G1O; X-ray; 2.70 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G1R; X-ray; 2.42 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G1S; X-ray; 2.50 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G1Y; X-ray; 2.50 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G20; X-ray; 2.40 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G21; X-ray; 2.20 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G22; X-ray; 2.50 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G24; X-ray; 1.90 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G26; X-ray; 2.10 A; A/B=74-406.[ExPASy / RCSB / EBI]
2G27; X-ray; 2.90 A; A/B=74-406.[ExPASy / RCSB / EBI]
2I4Q; X-ray; 2.30 A; A/B=71-406.[ExPASy / RCSB / EBI]
2IKO; X-ray; 1.90 A; A/B=67-406.[ExPASy / RCSB / EBI]
2IKU; X-ray; 2.60 A; A/B=67-406.[ExPASy / RCSB / EBI]
2IL2; X-ray; 2.24 A; A/B=67-406.[ExPASy / RCSB / EBI]
2REN; X-ray; 2.50 A; A=67-406.[ExPASy / RCSB / EBI]
2V0Z; X-ray; 2.20 A; C/O=67-406.[ExPASy / RCSB / EBI]
2V10; X-ray; 3.10 A; C/O=67-406.[ExPASy / RCSB / EBI]
2V11; X-ray; 3.10 A; C/O=67-406.[ExPASy / RCSB / EBI]
2V12; X-ray; 3.20 A; C/O=67-406.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1BBS; -.
1BIL; -.
1BIM; -.
1HRN; -.
1RNE; -.
2BKS; -.
2BKT; -.
2FS4; -.
2G1N; -.
2G1O; -.
2G1R; -.
2G1S; -.
2G1Y; -.
2G20; -.
2G21; -.
2G22; -.
2G24; -.
2G26; -.
2G27; -.
2I4Q; -.
2IKO; -.
2IKU; -.
2IL2; -.
2REN; -.
2V0Z; -.
2V10; -.
2V11; -.
2V12; -.
ModBase P00797.
Protein family/group databases
MEROPS A01.007; -.
PTM databases
GlycoSuiteDB P00797; -.
Organism-specific databases
HGNC HGNC:9958; REN.
GeneLynx REN; Homo sapiens.
GenAtlas REN.
HPA HPA005131; -.
MIM 179820; gene. [NCBI / EBI]
267430; phenotype. [NCBI / EBI]
Orphanet 3033; Renal tubular dysgenesis.
PharmGKB PA297; -.
GeneCards P00797.
Gene expression databases
ArrayExpress P00797; -.
CleanEx HS_REN; -.
GermOnline ENSG00000143839; Homo sapiens.
Ontologies
GO
GO:0005615; Cellular component: extracellular space (inferred from direct assay from HGNC).
GO:0005102; Molecular function: receptor binding (inferred from physical interaction from HGNC).
GO:0004195; Molecular function: renin activity (inferred from direct assay from HGNC).
GO:0002003; Biological process: angiotensin maturation (inferred from direct assay from HGNC).
GO:0043408; Biological process: regulation of MAPKKK cascade (inferred from direct assay from HGNC).
QuickGo view.
Family and domain databases
InterPro IPR001969; Pept_Asp_AS.
IPR009007; Pept_Aspartc_cat.
IPR001461; Peptidase_A1.
IPR012848; Propep_A1.
Graphical view of domain structure.
Gene3D G3DSA:2.40.70.10; Pept_Aspartc_cat; 1.
PANTHER PTHR13683; Peptidase_A1; 1.
Pfam PF07966; A1_Propeptide; 1.
PF00026; Asp; 1.
Pfam graphical view of domain structure.
PRINTS PR00792; PEPSIN.
PROSITE PS00141; ASP_PROTEASE; 2.
BLOCKS P00797.
Genome annotation databases
Ensembl ENSG00000143839; Homo sapiens. [Contig view]
GeneID 5972; -.
KEGG hsa:5972; -.
Other
DrugBank DB01258; Aliskiren.
DB00212; Remikiren.
LinkHub P00797; -.
SOURCE REN; Homo sapiens.
ProtoNet P00797.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Aspartyl protease; Cleavage on pair of basic residues; Direct protein sequencing; Disease mutation; Glycoprotein; Hydrolase; Membrane; Polymorphism; Protease; Secreted; Signal; Zymogen.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    23  23      
PROPEP   24    66  43     Activation peptide. PRO_0000026081
CHAIN   67   406  340     Renin. PRO_0000026082
ACT_SITE   104   104         
ACT_SITE   292   292         
CARBOHYD   71    71        N-linked (GlcNAc...). 
CARBOHYD   141   141        N-linked (GlcNAc...). 
DISULFID   117   124         
DISULFID   283   287         
DISULFID   325   362         
VAR_SEQ   231   233        Missing (in isoform 2). VSP_012899
VARIANT   33    33  1     R -> W (in dbSNP:rs11571098 [NCBI]). VAR_020375 
VARIANT   104   104  1     D -> N (in RTD). VAR_035088 [3D]
VARIANT   160   160  1     Q -> K (in dbSNP:rs11571083 [NCBI]). VAR_029171 [3D]
VARIANT   217   217  1     G -> R (in dbSNP:rs11571117 [NCBI]). VAR_020376 [3D]
VARIANT   230   230  1     R -> K (in RTD). VAR_035087 [3D]
CONFLICT   55    55        R -> S (in Ref. 2; AAA60364). 
CONFLICT   189   189        E -> Q (in Ref. 2; AAA60364). 
CONFLICT   304   304        S -> C (in Ref. 2; AAA60364). 
CONFLICT   351   351        V -> I (in Ref. 7). 
STRAND   74    81  8      
TURN   82    84  3      
STRAND   85    92  8      
TURN   93    96  4      
STRAND   97   104  8      
STRAND   110   114  5      
HELIX   122   125  4      
HELIX   132   134  3      
STRAND   139   149  11      
STRAND   152   165  14      
STRAND   168   179  12      
HELIX   182   185  4      
STRAND   192   195  4      
HELIX   199   201  3      
HELIX   203   205  3      
HELIX   209   214  6      
TURN   215   217  3      
STRAND   219   228  10      
STRAND   240   246  7      
HELIX   249   251  3      
STRAND   252   260  9      
STRAND   268   271  4      
STRAND   273   276  4      
STRAND   279   283  5      
STRAND   287   291  5      
STRAND   296   300  5      
HELIX   302   312  11      
STRAND   321   324  4      
TURN   325   327  3      
HELIX   328   330  3      
STRAND   334   338  5      
STRAND   341   345  5      
HELIX   347   350  4      
STRAND   360   368  9      
TURN   373   375  3      
STRAND   379   381  3