RENI_HUMAN
ID RENI_HUMAN Reviewed; 406 AA.
AC P00797; Q6FI38; Q6T5C2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 237.
DE RecName: Full=Renin {ECO:0000303|PubMed:6324167};
DE EC=3.4.23.15 {ECO:0000269|PubMed:12045255, ECO:0000269|PubMed:20927107};
DE AltName: Full=Angiotensinogenase;
DE Flags: Precursor;
GN Name=REN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=6324167; DOI=10.1073/pnas.80.24.7405;
RA Imai T., Miyazaki H., Hirose S., Hori H., Hayashi T., Kageyama R.,
RA Ohkubo H., Nakanishi S., Murakami K.;
RT "Cloning and sequence analysis of cDNA for human renin precursor.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:7405-7409(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RX PubMed=3530608; DOI=10.1042/cs0710345;
RA Morris B.J.;
RT "New possibilities for intracellular renin and inactive renin now that the
RT structure of the human renin gene has been elucidated.";
RL Clin. Sci. 71:345-355(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Fetal liver;
RX PubMed=6391881; DOI=10.1089/dna.1.1984.3.457;
RA Hardman J.A., Hort Y.J., Catanzaro D.F., Tellam J.T., Baxter J.D.,
RA Morris B.J., Shine J.;
RT "Primary structure of the human renin gene.";
RL DNA 3:457-468(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D.,
RA Toth E.J., Krauss R.M., Nickerson D.A.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Ovary;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 108-406 (ISOFORM 1).
RX PubMed=6138751; DOI=10.1093/nar/11.20.7181;
RA Soubrier F., Panthier J.-J., Corvol P., Rougeon F.;
RT "Molecular cloning and nucleotide sequence of a human renin cDNA
RT fragment.";
RL Nucleic Acids Res. 11:7181-7190(1983).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
RX PubMed=3032746; DOI=10.1016/0378-1119(86)90393-8;
RA Fukamizu A., Nishi K., Nishimatsu S., Miyazaki H., Hirose S., Murakami K.;
RT "Human renin gene of renin-secreting tumor.";
RL Gene 49:139-145(1986).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
RX PubMed=2540188; DOI=10.1016/s0021-9258(18)83241-0;
RA Burt D.W., Nakamura N., Kelley P., Dzau V.J.;
RT "Identification of negative and positive regulatory elements in the human
RT renin gene.";
RL J. Biol. Chem. 264:7357-7362(1989).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
RX PubMed=3516796; DOI=10.1016/0378-1119(86)90270-2;
RA Soubrier F., Panthier J.J., Houot A.-M., Rougeon F., Corvol P.;
RT "Segmental homology between the promoter region of the human renin gene and
RT the mouse ren1 and ren2 promoter regions.";
RL Gene 41:85-92(1986).
RN [13]
RP PROTEIN SEQUENCE OF 24-42 AND 67-86.
RX PubMed=2016271; DOI=10.1093/oxfordjournals.jbchem.a123347;
RA Ishizuka Y., Shoda A., Yoshida S., Kawamura Y., Haraguchi K., Murakami K.;
RT "Isolation and characterization of recombinant human prorenin in Chinese
RT hamster ovary cells.";
RL J. Biochem. 109:30-35(1991).
RN [14]
RP INTERACTION WITH ATP6AP2, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=12045255; DOI=10.1172/jci14276;
RA Nguyen G., Delarue F., Burckle C., Bouzhir L., Giller T., Sraer J.-D.;
RT "Pivotal role of the renin/prorenin receptor in angiotensin II production
RT and cellular responses to renin.";
RL J. Clin. Invest. 109:1417-1427(2002).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND GLYCOSYLATION AT ASN-71 AND
RP ASN-141.
RX PubMed=2493678; DOI=10.1126/science.2493678;
RA Sielecki A.R., Hayakawa K., Fujinaga M., Murphy M.E.P., Fraser M.,
RA Muir A.K., Carilli C.T., Lewicki J.A., Baxter J.D., James M.N.G.;
RT "Structure of recombinant human renin, a target for cardiovascular-active
RT drugs, at 2.5-A resolution.";
RL Science 243:1346-1351(1989).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=1608447; DOI=10.1038/357466a0;
RA Dhanaraj V., Dealwis C.G., Frazao C., Badasso M., Sibanda B.L.,
RA Tickle I.J., Cooper J.B., Driessen H.P.C., Newman M., Aguilar C.,
RA Wood S.P., Blundell T.L., Hobart P.M., Geoghegan K.F., Ammirati M.J.,
RA Danley D.E., O'Connor B.A., Hoover D.J.;
RT "X-ray analyses of peptide-inhibitor complexes define the structural basis
RT of specificity for human and mouse renins.";
RL Nature 357:466-472(1992).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (4.33 ANGSTROMS) OF 24-406 OF MUTANT ALA-292 IN
RP COMPLEX WITH ANGIOTENSINOGEN, DISULFIDE BONDS, FUNCTION, AND CATALYTIC
RP ACTIVITY.
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 [18]
RP VARIANTS RTD ASN-104 AND LYS-230.
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., Delezoide A.-L.,
RA Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., Joubert M.,
RA Antignac C., Gubler M.-C.;
RT "Mutations in genes in the renin-angiotensin system are associated with
RT autosomal recessive renal tubular dysgenesis.";
RL Nat. Genet. 37:964-968(2005).
RN [19]
RP VARIANT ADTKD4 ARG-16, AND CHARACTERIZATION OF VARIANT ADTKD4 ARG-16.
RX PubMed=19664745; DOI=10.1016/j.ajhg.2009.07.010;
RA Zivna M., Hulkova H., Matignon M., Hodanova K., Vylet'al P., Kalbacova M.,
RA Baresova V., Sikora J., Blazkova H., Zivny J., Ivanek R., Stranecky V.,
RA Sovova J., Claes K., Lerut E., Fryns J.P., Hart P.S., Hart T.C.,
RA Adams J.N., Pawtowski A., Clemessy M., Gasc J.M., Guebler M.C.,
RA Antignac C., Elleder M., Kapp K., Grimbert P., Bleyer A.J., Kmoch S.;
RT "Dominant renin gene mutations associated with early-onset hyperuricemia,
RT anemia, and chronic kidney failure.";
RL Am. J. Hum. Genet. 85:204-213(2009).
CC -!- FUNCTION: Renin is a highly specific endopeptidase, whose only known
CC function is to generate angiotensin I from angiotensinogen in the
CC plasma, initiating a cascade of reactions that produce an elevation of
CC blood pressure and increased sodium retention by the kidney.
CC {ECO:0000269|PubMed:12045255, ECO:0000269|PubMed:20927107}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of Leu-|-Xaa bond in angiotensinogen to generate
CC angiotensin I.; EC=3.4.23.15; Evidence={ECO:0000269|PubMed:12045255,
CC ECO:0000269|PubMed:20927107};
CC -!- ACTIVITY REGULATION: Interaction with ATP6AP2 results in a 5-fold
CC increased efficiency in angiotensinogen processing.
CC {ECO:0000269|PubMed:12045255}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1 uM for angiotensinogen (in absence of ATP6AP2)
CC {ECO:0000269|PubMed:12045255};
CC KM=0.15 uM for angiotensinogen (in presence of membrane-bound
CC ATP6AP2) {ECO:0000269|PubMed:12045255};
CC -!- SUBUNIT: Interacts with ATP6AP2. {ECO:0000269|PubMed:12045255}.
CC -!- INTERACTION:
CC P00797; P01019: AGT; NbExp=2; IntAct=EBI-715794, EBI-751728;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12045255}. Membrane
CC {ECO:0000269|PubMed:12045255}. Note=Associated to membranes via binding
CC to ATP6AP2. {ECO:0000269|PubMed:12045255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P00797-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00797-2; Sequence=VSP_012899;
CC -!- DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal
CC recessive severe disorder of renal tubular development characterized by
CC persistent fetal anuria and perinatal death, probably due to pulmonary
CC hypoplasia from early-onset oligohydramnios (the Potter phenotype).
CC {ECO:0000269|PubMed:16116425}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Tubulointerstitial kidney disease, autosomal dominant, 4
CC (ADTKD4) [MIM:613092]: A form of autosomal dominant tubulointerstitial
CC kidney disease, a genetically heterogeneous disorder characterized by
CC slowly progressive loss of kidney function, bland urinary sediment,
CC hyperuricemia, absent or mildly increased albuminuria, lack of severe
CC hypertension during the early stages, and normal or small kidneys on
CC ultrasound. Renal histology shows variable abnormalities including
CC interstitial fibrosis with tubular atrophy, microcystic dilatation of
CC the tubules, thickening of tubular basement membranes, medullary cysts,
CC and secondary glomerulosclerotic or glomerulocystic changes with
CC abnormal glomerular tufting. There is significant variability, as well
CC as incomplete penetrance. {ECO:0000269|PubMed:19664745}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Renin entry;
CC URL="https://en.wikipedia.org/wiki/Renin";
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DR EMBL; L00073; AAA60363.1; -; Genomic_DNA.
DR EMBL; L00064; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00065; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00066; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00067; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00068; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00069; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00070; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00071; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; L00072; AAA60363.1; JOINED; Genomic_DNA.
DR EMBL; M26901; AAA60364.1; -; Genomic_DNA.
DR EMBL; M26899; AAA60364.1; JOINED; Genomic_DNA.
DR EMBL; M26900; AAA60364.1; JOINED; Genomic_DNA.
DR EMBL; M10152; AAD03461.1; -; Genomic_DNA.
DR EMBL; M10030; AAD03461.1; JOINED; Genomic_DNA.
DR EMBL; M10128; AAD03461.1; JOINED; Genomic_DNA.
DR EMBL; M10150; AAD03461.1; JOINED; Genomic_DNA.
DR EMBL; M10151; AAD03461.1; JOINED; Genomic_DNA.
DR EMBL; AY436324; AAR03502.1; -; Genomic_DNA.
DR EMBL; CR536498; CAG38737.1; -; mRNA.
DR EMBL; EU332871; ABY87560.1; -; Genomic_DNA.
DR EMBL; AL592114; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592146; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033474; AAH33474.1; -; mRNA.
DR EMBL; BC047752; AAH47752.1; -; mRNA.
DR EMBL; M15410; AAA60263.1; -; Genomic_DNA.
DR EMBL; M26440; AAA60365.1; -; Genomic_DNA.
DR EMBL; M13253; AAA60262.1; -; Genomic_DNA.
DR CCDS; CCDS30981.1; -. [P00797-1]
DR PIR; A21454; REHUK.
DR RefSeq; NP_000528.1; NM_000537.3. [P00797-1]
DR PDB; 1BBS; X-ray; 2.80 A; A/B=67-406.
DR PDB; 1BIL; X-ray; 2.40 A; A/B=70-406.
DR PDB; 1BIM; X-ray; 2.80 A; A/B=70-406.
DR PDB; 1HRN; X-ray; 1.80 A; A/B=70-406.
DR PDB; 1RNE; X-ray; 2.40 A; A=67-406.
DR PDB; 2BKS; X-ray; 2.20 A; A/B=67-406.
DR PDB; 2BKT; X-ray; 2.30 A; A/B=67-406.
DR PDB; 2FS4; X-ray; 2.20 A; A/B=74-406.
DR PDB; 2G1N; X-ray; 2.90 A; A/B=74-406.
DR PDB; 2G1O; X-ray; 2.70 A; A/B=74-406.
DR PDB; 2G1R; X-ray; 2.42 A; A/B=74-406.
DR PDB; 2G1S; X-ray; 2.50 A; A/B=74-406.
DR PDB; 2G1Y; X-ray; 2.50 A; A/B=74-406.
DR PDB; 2G20; X-ray; 2.40 A; A/B=74-406.
DR PDB; 2G21; X-ray; 2.20 A; A/B=74-406.
DR PDB; 2G22; X-ray; 2.50 A; A/B=74-406.
DR PDB; 2G24; X-ray; 1.90 A; A/B=74-406.
DR PDB; 2G26; X-ray; 2.10 A; A/B=74-406.
DR PDB; 2G27; X-ray; 2.90 A; A/B=74-406.
DR PDB; 2I4Q; X-ray; 2.30 A; A/B=73-406.
DR PDB; 2IKO; X-ray; 1.90 A; A/B=67-406.
DR PDB; 2IKU; X-ray; 2.60 A; A/B=67-406.
DR PDB; 2IL2; X-ray; 2.24 A; A/B=67-406.
DR PDB; 2REN; X-ray; 2.50 A; A=67-406.
DR PDB; 2V0Z; X-ray; 2.20 A; C/O=67-406.
DR PDB; 2V10; X-ray; 3.10 A; C/O=67-406.
DR PDB; 2V11; X-ray; 3.10 A; C/O=67-406.
DR PDB; 2V12; X-ray; 3.20 A; C/O=67-406.
DR PDB; 2V13; X-ray; 2.80 A; A=67-406.
DR PDB; 2V16; X-ray; 2.80 A; C/O=67-406.
DR PDB; 2X0B; X-ray; 4.33 A; A/C/E/G=24-406.
DR PDB; 3D91; X-ray; 2.20 A; A/B=67-406.
DR PDB; 3G6Z; X-ray; 2.00 A; A/B=67-406.
DR PDB; 3G70; X-ray; 2.00 A; A/B=67-406.
DR PDB; 3G72; X-ray; 1.90 A; A/B=67-406.
DR PDB; 3GW5; X-ray; 2.00 A; A/B=70-406.
DR PDB; 3K1W; X-ray; 1.50 A; A/B=67-406.
DR PDB; 3KM4; X-ray; 1.90 A; A/B=70-406.
DR PDB; 3O9L; X-ray; 2.40 A; A/C=67-232, B/D=237-406.
DR PDB; 3OAD; X-ray; 2.17 A; A/C=67-232, B/D=237-406.
DR PDB; 3OAG; X-ray; 2.30 A; A/C=67-232, B/D=237-406.
DR PDB; 3OOT; X-ray; 2.55 A; A/B=67-406.
DR PDB; 3OQF; X-ray; 2.78 A; A/B=67-406.
DR PDB; 3OQK; X-ray; 2.90 A; A/B=67-406.
DR PDB; 3OWN; X-ray; 2.00 A; A/B=67-406.
DR PDB; 3Q3T; X-ray; 2.60 A; A/B=67-406.
DR PDB; 3Q4B; X-ray; 2.19 A; A/B=67-406.
DR PDB; 3Q5H; X-ray; 2.16 A; A/B=67-406.
DR PDB; 3SFC; X-ray; 2.10 A; A/B=67-406.
DR PDB; 3VCM; X-ray; 2.93 A; A/B=67-406, P/Q=24-66.
DR PDB; 3VSW; X-ray; 3.00 A; A/B=67-406.
DR PDB; 3VSX; X-ray; 2.80 A; A/B=67-406.
DR PDB; 3VUC; X-ray; 2.60 A; A/B=67-406.
DR PDB; 3VYD; X-ray; 2.81 A; A/B=67-406.
DR PDB; 3VYE; X-ray; 2.70 A; A/B=67-406.
DR PDB; 3VYF; X-ray; 2.80 A; A/B=67-406.
DR PDB; 4AMT; X-ray; 2.60 A; A=24-406.
DR PDB; 4GJ5; X-ray; 2.40 A; A/B=67-406.
DR PDB; 4GJ6; X-ray; 2.58 A; A/B=67-406.
DR PDB; 4GJ7; X-ray; 2.80 A; A/B=67-406.
DR PDB; 4GJ8; X-ray; 2.50 A; A/B=67-406.
DR PDB; 4GJ9; X-ray; 2.60 A; A/B=67-406.
DR PDB; 4GJA; X-ray; 2.60 A; A/B=67-406.
DR PDB; 4GJB; X-ray; 2.75 A; A/B=67-406.
DR PDB; 4GJC; X-ray; 2.40 A; A/B=67-406.
DR PDB; 4GJD; X-ray; 2.65 A; A/B=67-406.
DR PDB; 4PYV; X-ray; 2.65 A; A/B=67-406.
DR PDB; 4Q1N; X-ray; 2.09 A; A/B=67-406.
DR PDB; 4RYC; X-ray; 2.45 A; A/B=67-406.
DR PDB; 4RYG; X-ray; 2.65 A; A/B=67-406.
DR PDB; 4RZ1; X-ray; 2.60 A; A/B=67-406.
DR PDB; 4S1G; X-ray; 2.10 A; A/B=67-406.
DR PDB; 4XX3; X-ray; 2.40 A; A/B=67-406.
DR PDB; 4XX4; X-ray; 2.40 A; A/B=67-406.
DR PDB; 5KOQ; X-ray; 2.70 A; A/B=70-406.
DR PDB; 5KOS; X-ray; 2.41 A; A/B=70-406.
DR PDB; 5KOT; X-ray; 2.10 A; A/B=70-406.
DR PDB; 5SXN; X-ray; 2.10 A; A/B=68-406.
DR PDB; 5SY2; X-ray; 2.25 A; A/B=67-406.
DR PDB; 5SY3; X-ray; 2.30 A; A/B=68-406.
DR PDB; 5SZ9; X-ray; 2.85 A; A/B=68-406.
DR PDB; 5T4S; X-ray; 2.64 A; A/B=68-406.
DR PDB; 5TMG; X-ray; 2.20 A; A/B=70-406.
DR PDB; 5TMK; X-ray; 2.65 A; A/B=70-406.
DR PDB; 5V8V; X-ray; 2.60 A; A/B=70-406.
DR PDB; 5VPM; X-ray; 2.90 A; A/B=70-406.
DR PDB; 5VRP; X-ray; 3.22 A; A/B=70-406.
DR PDB; 6I3F; X-ray; 2.55 A; B=67-406.
DR PDBsum; 1BBS; -.
DR PDBsum; 1BIL; -.
DR PDBsum; 1BIM; -.
DR PDBsum; 1HRN; -.
DR PDBsum; 1RNE; -.
DR PDBsum; 2BKS; -.
DR PDBsum; 2BKT; -.
DR PDBsum; 2FS4; -.
DR PDBsum; 2G1N; -.
DR PDBsum; 2G1O; -.
DR PDBsum; 2G1R; -.
DR PDBsum; 2G1S; -.
DR PDBsum; 2G1Y; -.
DR PDBsum; 2G20; -.
DR PDBsum; 2G21; -.
DR PDBsum; 2G22; -.
DR PDBsum; 2G24; -.
DR PDBsum; 2G26; -.
DR PDBsum; 2G27; -.
DR PDBsum; 2I4Q; -.
DR PDBsum; 2IKO; -.
DR PDBsum; 2IKU; -.
DR PDBsum; 2IL2; -.
DR PDBsum; 2REN; -.
DR PDBsum; 2V0Z; -.
DR PDBsum; 2V10; -.
DR PDBsum; 2V11; -.
DR PDBsum; 2V12; -.
DR PDBsum; 2V13; -.
DR PDBsum; 2V16; -.
DR PDBsum; 2X0B; -.
DR PDBsum; 3D91; -.
DR PDBsum; 3G6Z; -.
DR PDBsum; 3G70; -.
DR PDBsum; 3G72; -.
DR PDBsum; 3GW5; -.
DR PDBsum; 3K1W; -.
DR PDBsum; 3KM4; -.
DR PDBsum; 3O9L; -.
DR PDBsum; 3OAD; -.
DR PDBsum; 3OAG; -.
DR PDBsum; 3OOT; -.
DR PDBsum; 3OQF; -.
DR PDBsum; 3OQK; -.
DR PDBsum; 3OWN; -.
DR PDBsum; 3Q3T; -.
DR PDBsum; 3Q4B; -.
DR PDBsum; 3Q5H; -.
DR PDBsum; 3SFC; -.
DR PDBsum; 3VCM; -.
DR PDBsum; 3VSW; -.
DR PDBsum; 3VSX; -.
DR PDBsum; 3VUC; -.
DR PDBsum; 3VYD; -.
DR PDBsum; 3VYE; -.
DR PDBsum; 3VYF; -.
DR PDBsum; 4AMT; -.
DR PDBsum; 4GJ5; -.
DR PDBsum; 4GJ6; -.
DR PDBsum; 4GJ7; -.
DR PDBsum; 4GJ8; -.
DR PDBsum; 4GJ9; -.
DR PDBsum; 4GJA; -.
DR PDBsum; 4GJB; -.
DR PDBsum; 4GJC; -.
DR PDBsum; 4GJD; -.
DR PDBsum; 4PYV; -.
DR PDBsum; 4Q1N; -.
DR PDBsum; 4RYC; -.
DR PDBsum; 4RYG; -.
DR PDBsum; 4RZ1; -.
DR PDBsum; 4S1G; -.
DR PDBsum; 4XX3; -.
DR PDBsum; 4XX4; -.
DR PDBsum; 5KOQ; -.
DR PDBsum; 5KOS; -.
DR PDBsum; 5KOT; -.
DR PDBsum; 5SXN; -.
DR PDBsum; 5SY2; -.
DR PDBsum; 5SY3; -.
DR PDBsum; 5SZ9; -.
DR PDBsum; 5T4S; -.
DR PDBsum; 5TMG; -.
DR PDBsum; 5TMK; -.
DR PDBsum; 5V8V; -.
DR PDBsum; 5VPM; -.
DR PDBsum; 5VRP; -.
DR PDBsum; 6I3F; -.
DR AlphaFoldDB; P00797; -.
DR SMR; P00797; -.
DR BioGRID; 111904; 11.
DR DIP; DIP-59219N; -.
DR ELM; P00797; -.
DR IntAct; P00797; 5.
DR STRING; 9606.ENSP00000272190; -.
DR BindingDB; P00797; -.
DR ChEMBL; CHEMBL286; -.
DR DrugBank; DB07113; (2S)-6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-2-(3,5-DIFLUOROPHENYL)-4-(3-METHOXYPROPYL)-2H-1,4-BENZOXAZIN-3(4H)-ONE.
DR DrugBank; DB04387; 1-Hydroxy-2-Amino-3-Cyclohexylpropane.
DR DrugBank; DB03968; 1-Methyl-2-Oxy-5,5-Dimethyl Pyrrolidine.
DR DrugBank; DB03736; 2-Cyclopropylmethylenepropanal.
DR DrugBank; DB03024; 2-Methyl-3-(2-Aminothiazolo)Propanal.
DR DrugBank; DB02803; 3-Phenyl-1,2-Propandiol.
DR DrugBank; DB07244; 5-{4-[(3,5-DIFLUOROBENZYL)AMINO]PHENYL}-6-ETHYLPYRIMIDINE-2,4-DIAMINE.
DR DrugBank; DB07174; 6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-4-(3-METHOXYPROPYL)-2,2-DIMETHYL-2H-1,4-BENZOXAZIN-3(4H)-ONE.
DR DrugBank; DB08099; 6-ethyl-5-[(2S)-1-(3-methoxypropyl)-2-phenyl-1,2,3,4-tetrahydroquinolin-7-yl]pyrimidine-2,4-diamine.
DR DrugBank; DB06967; 6-ETHYL-5-[9-(3-METHOXYPROPYL)-9H-CARBAZOL-2-YL]PYRIMIDINE-2,4-DIAMINE.
DR DrugBank; DB09026; Aliskiren.
DR DrugBank; DB03395; Enalkiren.
DR DrugBank; DB02296; Isoamyl alcohol.
DR DrugBank; DB00722; Lisinopril.
DR DrugBank; DB00350; Minoxidil.
DR DrugBank; DB01844; N,N-dimethylformamide.
DR DrugBank; DB04379; N-Methyl-N-(Methylbenzyl)Formamide.
DR DrugBank; DB06899; N-{2-[6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-2,2-DIMETHYL-3-OXO-2,3-DIHYDRO-4H-1,4-BENZOTHIAZIN-4-YL]ETHYL}ACETAMIDE.
DR DrugBank; DB07059; N-{2-[6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-2,2-DIMETHYL-3-OXO-2,3-DIHYDRO-4H-1,4-BENZOXAZIN-4-YL]ETHYL}ACETAMIDE.
DR DrugBank; DB00212; Remikiren.
DR DrugBank; DB05203; SPP1148.
DR DrugCentral; P00797; -.
DR GuidetoPHARMACOLOGY; 2413; -.
DR MEROPS; A01.007; -.
DR GlyConnect; 513; 19 N-Linked glycans.
DR GlyGen; P00797; 3 sites, 32 N-linked glycans (1 site).
DR iPTMnet; P00797; -.
DR PhosphoSitePlus; P00797; -.
DR BioMuta; REN; -.
DR DMDM; 132326; -.
DR MassIVE; P00797; -.
DR PaxDb; P00797; -.
DR PeptideAtlas; P00797; -.
DR PRIDE; P00797; -.
DR ProteomicsDB; 51287; -. [P00797-1]
DR ProteomicsDB; 51288; -. [P00797-2]
DR Antibodypedia; 1026; 780 antibodies from 40 providers.
DR DNASU; 5972; -.
DR Ensembl; ENST00000272190.9; ENSP00000272190.8; ENSG00000143839.15. [P00797-1]
DR GeneID; 5972; -.
DR KEGG; hsa:5972; -.
DR MANE-Select; ENST00000272190.9; ENSP00000272190.8; NM_000537.4; NP_000528.1.
DR UCSC; uc001haq.3; human. [P00797-1]
DR CTD; 5972; -.
DR DisGeNET; 5972; -.
DR GeneCards; REN; -.
DR GeneReviews; REN; -.
DR HGNC; HGNC:9958; REN.
DR HPA; ENSG00000143839; Tissue enriched (kidney).
DR MalaCards; REN; -.
DR MIM; 179820; gene.
DR MIM; 267430; phenotype.
DR MIM; 613092; phenotype.
DR neXtProt; NX_P00797; -.
DR OpenTargets; ENSG00000143839; -.
DR Orphanet; 217330; REN-related autosomal dominant tubulointerstitial kidney disease.
DR Orphanet; 97369; Renal tubular dysgenesis of genetic origin.
DR PharmGKB; PA297; -.
DR VEuPathDB; HostDB:ENSG00000143839; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000157898; -.
DR HOGENOM; CLU_013253_3_3_1; -.
DR InParanoid; P00797; -.
DR OMA; SWQITMK; -.
DR OrthoDB; 1619495at2759; -.
DR PhylomeDB; P00797; -.
DR TreeFam; TF314990; -.
DR BRENDA; 3.4.23.15; 2681.
DR PathwayCommons; P00797; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SignaLink; P00797; -.
DR SIGNOR; P00797; -.
DR BioGRID-ORCS; 5972; 13 hits in 1070 CRISPR screens.
DR EvolutionaryTrace; P00797; -.
DR GeneWiki; Renin; -.
DR GenomeRNAi; 5972; -.
DR Pharos; P00797; Tclin.
DR PRO; PR:P00797; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P00797; protein.
DR Bgee; ENSG00000143839; Expressed in decidua and 81 other tissues.
DR ExpressionAtlas; P00797; baseline and differential.
DR Genevisible; P00797; HS.
DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:HGNC-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0008233; F:peptidase activity; IDA:HGNC-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:HGNC-UCL.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IEA:Ensembl.
DR GO; GO:0002003; P:angiotensin maturation; IDA:HGNC-UCL.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0042756; P:drinking behavior; IEA:Ensembl.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IMP:BHF-UCL.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0001823; P:mesonephros development; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IDA:HGNC-UCL.
DR GO; GO:0008217; P:regulation of blood pressure; TAS:ProtInc.
DR GO; GO:0043408; P:regulation of MAPK cascade; IDA:HGNC-UCL.
DR GO; GO:0002018; P:renin-angiotensin regulation of aldosterone production; IEA:Ensembl.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0070305; P:response to cGMP; IEA:Ensembl.
DR GO; GO:0035902; P:response to immobilization stress; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR CDD; cd05487; renin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR012848; Aspartic_peptidase_N.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR034135; Renin-like_dom.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF07966; A1_Propeptide; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Aspartyl protease;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Hydrolase; Membrane;
KW Protease; Reference proteome; Secreted; Signal; Zymogen.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:2016271"
FT PROPEP 24..66
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:2016271"
FT /id="PRO_0000026081"
FT CHAIN 67..406
FT /note="Renin"
FT /id="PRO_0000026082"
FT DOMAIN 86..403
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 104
FT /evidence="ECO:0000269|PubMed:20927107"
FT ACT_SITE 292
FT /evidence="ECO:0000269|PubMed:20927107"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2493678"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2493678"
FT DISULFID 117..124
FT /evidence="ECO:0000269|PubMed:20927107"
FT DISULFID 283..287
FT /evidence="ECO:0000269|PubMed:20927107"
FT DISULFID 325..362
FT /evidence="ECO:0000269|PubMed:20927107"
FT VAR_SEQ 231..233
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_012899"
FT VARIANT 16
FT /note="L -> R (in ADTKD4; affects ER translocation and
FT processing of nascent preprorenin, resulting in abolished
FT prorenin and renin biosynthesis and secretion;
FT dbSNP:rs121917743)"
FT /evidence="ECO:0000269|PubMed:19664745"
FT /id="VAR_063770"
FT VARIANT 33
FT /note="R -> W (in dbSNP:rs11571098)"
FT /id="VAR_020375"
FT VARIANT 104
FT /note="D -> N (in RTD; dbSNP:rs868694193)"
FT /evidence="ECO:0000269|PubMed:16116425"
FT /id="VAR_035088"
FT VARIANT 160
FT /note="Q -> K (in dbSNP:rs11571083)"
FT /id="VAR_029171"
FT VARIANT 217
FT /note="G -> R (in dbSNP:rs11571117)"
FT /id="VAR_020376"
FT VARIANT 230
FT /note="R -> K (in RTD; dbSNP:rs121917742)"
FT /evidence="ECO:0000269|PubMed:16116425"
FT /id="VAR_035087"
FT CONFLICT 55
FT /note="R -> S (in Ref. 2; AAA60364)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="E -> Q (in Ref. 2; AAA60364)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="S -> C (in Ref. 2; AAA60364)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="V -> I (in Ref. 9)"
FT /evidence="ECO:0000305"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:4AMT"
FT HELIX 42..49
FT /evidence="ECO:0007829|PDB:4AMT"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:3VCM"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:3VCM"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:3K1W"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:3K1W"
FT TURN 93..96
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:4AMT"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 139..149
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 152..165
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 168..179
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 189..195
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 203..205
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 209..215
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 219..228
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 233..236
FT /evidence="ECO:0007829|PDB:3GW5"
FT STRAND 240..246
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 252..260
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:1BBS"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 279..282
FT /evidence="ECO:0007829|PDB:3K1W"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:2G27"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 296..300
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:3SFC"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:2G27"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 325..330
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 334..338
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 360..368
FT /evidence="ECO:0007829|PDB:3K1W"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:3K1W"
FT HELIX 383..386
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 389..394
FT /evidence="ECO:0007829|PDB:3K1W"
FT TURN 395..398
FT /evidence="ECO:0007829|PDB:3K1W"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:3K1W"
SQ SEQUENCE 406 AA; 45057 MW; 5AFDF8E973B21EDA CRC64;
MDGWRRMPRW GLLLLLWGSC TFGLPTDTTT FKRIFLKRMP SIRESLKERG VDMARLGPEW
SQPMKRLTLG NTTSSVILTN YMDTQYYGEI GIGTPPQTFK VVFDTGSSNV WVPSSKCSRL
YTACVYHKLF DASDSSSYKH NGTELTLRYS TGTVSGFLSQ DIITVGGITV TQMFGEVTEM
PALPFMLAEF DGVVGMGFIE QAIGRVTPIF DNIISQGVLK EDVFSFYYNR DSENSQSLGG
QIVLGGSDPQ HYEGNFHYIN LIKTGVWQIQ MKGVSVGSST LLCEDGCLAL VDTGASYISG
STSSIEKLME ALGAKKRLFD YVVKCNEGPT LPDISFHLGG KEYTLTSADY VFQESYSSKK
LCTLAIHAMD IPPPTGPTWA LGATFIRKFY TEFDRRNNRI GFALAR
