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 24-JAN-2024, entry version 245. 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"; 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; 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 PDB; 7XGK; X-ray; 2.40 A; A/B=67-406. DR PDB; 7XGO; X-ray; 2.10 A; A/B=67-406. DR PDB; 7XGP; X-ray; 2.65 A; 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 PDBsum; 7XGK; -. DR PDBsum; 7XGO; -. DR PDBsum; 7XGP; -. 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 GlyCosmos; P00797; 2 sites, 32 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; 9606-ENSP00000272190; -. DR PeptideAtlas; P00797; -. DR ProteomicsDB; 51287; -. [P00797-1] DR ProteomicsDB; 51288; -. [P00797-2] DR Antibodypedia; 1026; 836 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 AGR; HGNC:9958; -. 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; KMPSIRD; -. DR OrthoDB; 1120702at2759; -. 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 1154 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 cell types or tissues. DR ExpressionAtlas; P00797; baseline and differential. DR GO; GO:0045177; C:apical part of cell; IDA:BHF-UCL. 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:0072051; P:juxtaglomerular apparatus development; 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; Acid Proteases; 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; BETA-SITE APP-CLEAVING ENZYME, ISOFORM A-RELATED; 1. DR PANTHER; PTHR47966:SF24; RENIN; 1. DR Pfam; PF07966; A1_Propeptide; 1. DR Pfam; PF00026; Asp; 1. DR PRINTS; PR00792; PEPSIN. DR SUPFAM; SSF50630; Acid proteases; 1. DR PROSITE; PS00141; ASP_PROTEASE; 2. DR PROSITE; PS51767; PEPTIDASE_A1; 1. DR Genevisible; P00797; HS. 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 //