ID CBR1_HUMAN Reviewed; 277 AA. AC P16152; B2RBZ7; B4DFK7; Q3LHW8; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 02-SEP-2026, entry version 244. DE RecName: Full=Carbonyl reductase [NADPH] 1 {ECO:0000305}; DE EC=1.1.1.184 {ECO:0000269|PubMed:17344335, ECO:0000269|PubMed:1921984, ECO:0000269|PubMed:7005231}; DE AltName: Full=15-hydroxyprostaglandin dehydrogenase [NADP(+)]; DE EC=1.1.1.196 {ECO:0000250|UniProtKB:Q28960}; DE EC=1.1.1.197 {ECO:0000269|PubMed:7005231}; DE AltName: Full=20-beta-hydroxysteroid dehydrogenase; DE AltName: Full=Alcohol dehydrogenase [NAD(P)+] CBR1; DE EC=1.1.1.71 {ECO:0000269|PubMed:7005231}; DE AltName: Full=NADPH-dependent carbonyl reductase 1; DE AltName: Full=Prostaglandin 9-ketoreductase {ECO:0000303|PubMed:1597188}; DE Short=PG-9-KR {ECO:0000303|PubMed:1597188}; DE AltName: Full=Prostaglandin-E(2) 9-reductase {ECO:0000250|UniProtKB:Q28960}; DE EC=1.1.1.189 {ECO:0000269|PubMed:17344335}; DE AltName: Full=Short chain dehydrogenase/reductase family 21C member 1; GN Name=CBR1 {ECO:0000312|HGNC:HGNC:1548}; Synonyms=CBR, CRN, SDR21C1; 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 [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Placenta; RX PubMed=3141401; DOI=10.1016/s0021-9258(18)37576-8; RA Wermuth B., Bohren K.M., Heinemann G., von Wartburg J.-P., Gabbay K.H.; RT "Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino RT acid sequence of the encoded protein."; RL J. Biol. Chem. 263:16185-16188(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Mammary gland; RX PubMed=2182121; DOI=10.1016/0167-4781(90)90050-c; RA Forrest G.L., Akman S., Krutzik S., Paxton R.J., Sparkes R.S., Doroshow J., RA Felsted R.L., Mohandas T., Bachur N.R.; RT "Induction of a human carbonyl reductase gene located on chromosome 21."; RL Biochim. Biophys. Acta 1048:149-155(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=1921984; RA Forrest G.L., Akman S., Doroshow J., Rivera H., Kaplan W.D.; RT "Genomic sequence and expression of a cloned human carbonyl reductase gene RT with daunorubicin reductase activity."; RL Mol. Pharmacol. 40:502-507(1991). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9740676; DOI=10.1006/geno.1998.5380; RA Watanabe K., Sugawara C., Ono A., Fukuzumi Y., Itakura S., Yamazaki M., RA Tashiro H., Osoegawa K., Soeda E., Nomura T.; RT "Mapping of a novel human carbonyl reductase, CBR3, and ribosomal RT pseudogenes to human chromosome 21q22.2."; RL Genomics 52:95-100(1998). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RA Terada T., Mizobuchi H.; RT "Human fetal brain carbonyl reductases."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT SER-131. RG SeattleSNPs variation discovery resource; RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; 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 [13] RP PARTIAL PROTEIN SEQUENCE, AND POST-TRANSLATIONAL MODIFICATION AT LYS-239. RX PubMed=8421682; DOI=10.1073/pnas.90.2.502; RA Krook M., Ghosh D., Stroemberg R., Carlquist M., Joernvall H.; RT "Carboxyethyllysine in a protein: native carbonyl reductase/NADP(+)- RT dependent prostaglandin dehydrogenase."; RL Proc. Natl. Acad. Sci. U.S.A. 90:502-506(1993). RN [14] RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=7005231; DOI=10.1016/s0021-9258(19)69950-3; RA Wermuth B.; RT "Purification and properties of an NADPH-dependent carbonyl reductase from RT human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic RT ketone reductase."; RL J. Biol. Chem. 256:1206-1213(1981). RN [15] RP TISSUE SPECIFICITY. RX PubMed=1597188; DOI=10.1111/j.1432-1033.1992.tb16952.x; RA Schieber A., Frank R.W., Ghisla S.; RT "Purification and properties of prostaglandin 9-ketoreductase from pig and RT human kidney. Identity with human carbonyl reductase."; RL Eur. J. Biochem. 206:491-502(1992). RN [16] RP ACTIVITY REGULATION, FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF RP VARIANT ILE-88. RX PubMed=18449627; DOI=10.1007/s11095-008-9592-5; RA Gonzalez-Covarrubias V., Kalabus J.L., Blanco J.G.; RT "Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the RT cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER)."; RL Pharm. Res. 25:1730-1734(2008). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28878267; DOI=10.1038/s41598-017-10410-1; RA Morgan R.A., Beck K.R., Nixon M., Homer N.Z.M., Crawford A.A., Melchers D., RA Houtman R., Meijer O.C., Stomby A., Anderson A.J., Upreti R., Stimson R.H., RA Olsson T., Michoel T., Cohain A., Ruusalepp A., Schadt E.E., RA Bjoerkegren J.L.M., Andrew R., Kenyon C.J., Hadoke P.W.F., Odermatt A., RA Keen J.A., Walker B.R.; RT "Carbonyl reductase 1 catalyzes 20beta-reduction of glucocorticoids, RT modulating receptor activation and metabolic complications of obesity."; RL Sci. Rep. 7:10633-10633(2017). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 2-276 IN COMPLEX WITH THE RP SYNTHETIC INHIBITOR HYDROXY-PP AND NADP, IDENTIFICATION BY MASS RP SPECTROMETRY, PARTIAL PROTEIN SEQUENCE, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15799708; DOI=10.1371/journal.pbio.0030128; RA Tanaka M., Bateman R., Rauh D., Vaisberg E., Ramachandani S., Zhang C., RA Hansen K.C., Burlingame A.L., Trautman J.K., Shokat K.M., Adams C.L.; RT "An unbiased cell morphology-based screen for new, biologically active RT small molecules."; RL PLoS Biol. 3:E128-E128(2005). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP AND RP FORMALDEHYDE-GLUTATHIONE ADDUCT, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=17912391; DOI=10.1039/b707602a; RA Bateman R., Rauh D., Shokat K.M.; RT "Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane RT adduct."; RL Org. Biomol. Chem. 5:3363-3367(2007). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP, RP SUBSTRATE ANALOGS, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=18826943; DOI=10.1074/jbc.m807125200; RA Bateman R.L., Rauh D., Tavshanjian B., Shokat K.M.; RT "Human carbonyl reductase 1 is an S-nitrosoglutathione reductase."; RL J. Biol. Chem. 283:35756-35762(2008). RN [23] RP VARIANT ILE-88, CHARACTERIZATION OF VARIANT ILE-88, BIOPHYSICOCHEMICAL RP PROPERTIES, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY. RX PubMed=17344335; DOI=10.1124/dmd.107.014779; RA Gonzalez-Covarrubias V., Ghosh D., Lakhman S.S., Pendyala L., Blanco J.G.; RT "A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 RT V88I) impacts on catalytic activity and NADPH binding affinity."; RL Drug Metab. Dispos. 35:973-980(2007). CC -!- FUNCTION: NADPH-dependent reductase with broad substrate specificity. CC Catalyzes the reduction of a wide variety of carbonyl compounds CC including quinones, prostaglandins, menadione, plus various CC xenobiotics. Catalyzes the reduction of the antitumor anthracyclines CC doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol CC and daunorubicinol (PubMed:15799708, PubMed:17344335, PubMed:17912391, CC PubMed:18449627, PubMed:18826943, PubMed:1921984, PubMed:7005231). Can CC convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can CC bind glutathione, which explains its higher affinity for glutathione- CC conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione CC (PubMed:17344335, PubMed:18826943). In addition, participates in the CC glucocorticoid metabolism by catalyzing the NADPH-dependent CC cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or CC 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and CC NR3C2 in adipose tissue (PubMed:28878267). CC {ECO:0000250|UniProtKB:Q28960, ECO:0000269|PubMed:15799708, CC ECO:0000269|PubMed:17344335, ECO:0000269|PubMed:17912391, CC ECO:0000269|PubMed:18449627, ECO:0000269|PubMed:18826943, CC ECO:0000269|PubMed:1921984, ECO:0000269|PubMed:28878267, CC ECO:0000269|PubMed:7005231}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a secondary alcohol + NADP(+) = a ketone + NADPH + H(+); CC Xref=Rhea:RHEA:19257, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087, CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.184; Evidence={ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:1921984, ECO:0000269|PubMed:7005231}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a primary alcohol + NADP(+) = an aldehyde + NADPH + H(+); CC Xref=Rhea:RHEA:15937, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734, CC ChEBI:CHEBI:17478, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.71; CC Evidence={ECO:0000269|PubMed:7005231}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin F2alpha + NADP(+) = prostaglandin E2 + NADPH + CC H(+); Xref=Rhea:RHEA:24508, ChEBI:CHEBI:15378, ChEBI:CHEBI:57404, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:606564; CC EC=1.1.1.189; Evidence={ECO:0000269|PubMed:17344335}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24510; CC Evidence={ECO:0000250|UniProtKB:Q28960}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin E1 + NADP(+) = 15-oxoprostaglandin E1 + NADPH + CC H(+); Xref=Rhea:RHEA:11636, ChEBI:CHEBI:15378, ChEBI:CHEBI:57397, CC ChEBI:CHEBI:57401, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.197; Evidence={ECO:0000269|PubMed:7005231}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11637; CC Evidence={ECO:0000305|PubMed:7005231}; CC -!- CATALYTIC ACTIVITY: CC Reaction=menadione + NADPH + H(+) = menadiol + NADP(+); CC Xref=Rhea:RHEA:63492, ChEBI:CHEBI:6746, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:28869, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:15799708, ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18449627, CC ECO:0000269|PubMed:7005231}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin D2 + NADP(+) = 15-oxoprostaglandin D2 + NADPH + CC H(+); Xref=Rhea:RHEA:20744, ChEBI:CHEBI:15378, ChEBI:CHEBI:57406, CC ChEBI:CHEBI:57408, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.196; Evidence={ECO:0000250|UniProtKB:Q28960}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20745; CC Evidence={ECO:0000250|UniProtKB:Q28960}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin E2 + NADP(+) = 15-oxoprostaglandin E2 + NADPH + CC H(+); Xref=Rhea:RHEA:63476, ChEBI:CHEBI:15378, ChEBI:CHEBI:57400, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:606564; CC Evidence={ECO:0000250|UniProtKB:Q28960}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63477; CC Evidence={ECO:0000250|UniProtKB:Q28960}; CC -!- CATALYTIC ACTIVITY: CC Reaction=prostaglandin F2alpha + NADP(+) = 15-oxoprostaglandin F2alpha CC + NADPH + H(+); Xref=Rhea:RHEA:63480, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57404, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:133409; Evidence={ECO:0000250|UniProtKB:Q28960}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63481; CC Evidence={ECO:0000250|UniProtKB:Q28960}; CC -!- CATALYTIC ACTIVITY: CC Reaction=daunorubicin + NADPH + H(+) = 13-dihydrodaunorubicin + CC NADP(+); Xref=Rhea:RHEA:63504, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64677, ChEBI:CHEBI:75296; CC Evidence={ECO:0000269|PubMed:17344335, ECO:0000269|PubMed:18449627, CC ECO:0000269|PubMed:1921984, ECO:0000269|PubMed:7005231}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63505; CC Evidence={ECO:0000305|PubMed:17344335, ECO:0000305|PubMed:1921984}; CC -!- CATALYTIC ACTIVITY: CC Reaction=S-nitrosoglutathione + NADPH + H(+) = S- CC (hydroxysulfenamide)glutathione + NADP(+); Xref=Rhea:RHEA:63500, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, CC ChEBI:CHEBI:145544, ChEBI:CHEBI:229723; CC Evidence={ECO:0000269|PubMed:18826943}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cortisol + NADPH + H(+) = 20beta-dihydrocortisol + NADP(+); CC Xref=Rhea:RHEA:70215, ChEBI:CHEBI:15378, ChEBI:CHEBI:17650, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:139311; CC Evidence={ECO:0000269|PubMed:28878267}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70216; CC Evidence={ECO:0000305|PubMed:28878267}; CC -!- CATALYTIC ACTIVITY: CC Reaction=corticosterone + NADPH + H(+) = 20beta-dihydrocorticosterone + CC NADP(+); Xref=Rhea:RHEA:70219, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:189050; CC Evidence={ECO:0000250|UniProtKB:P48758}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70220; CC Evidence={ECO:0000250|UniProtKB:P48758}; CC -!- ACTIVITY REGULATION: Inhibited by quercetin, rutenin and its CC derivatives. {ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:18449627}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=30 uM for S-nitrosoglutathione {ECO:0000269|PubMed:18826943}; CC KM=22 uM for menadione {ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:18826943}; CC KM=309 uM for prostaglandin E2 {ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:18826943}; CC KM=450 uM for prostaglandin E1 {ECO:0000269|PubMed:7005231}; CC KM=4 mM for phenylglyoxal {ECO:0000269|PubMed:7005231}; CC KM=1.6 mM for 4-nitrobenzaldehyde {ECO:0000269|PubMed:7005231}; CC KM=17 uM for ubiquinone-1 {ECO:0000269|PubMed:7005231}; CC KM=173 uM for daunorubicin {ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:18826943}; CC KM=247 uM for NADPH {ECO:0000269|PubMed:17344335, CC ECO:0000269|PubMed:18826943}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15799708, CC ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18826943}. CC -!- INTERACTION: CC P16152; O75828: CBR3; NbExp=4; IntAct=EBI-351348, EBI-714504; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P16152-1; Sequence=Displayed; CC Name=2; CC IsoId=P16152-2; Sequence=VSP_054796, VSP_054797; CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level). CC {ECO:0000269|PubMed:1597188}. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) CC family. {ECO:0000305}. 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; J04056; AAA52070.1; -; mRNA. DR EMBL; M62420; AAA17881.1; -; Genomic_DNA. DR EMBL; AB003151; BAA33498.1; -; Genomic_DNA. DR EMBL; AP000688; BAA89424.1; -; Genomic_DNA. DR EMBL; AB124848; BAE45940.1; -; mRNA. DR EMBL; BT019843; AAV38646.1; -; mRNA. DR EMBL; CR541708; CAG46509.1; -; mRNA. DR EMBL; AK294142; BAG57468.1; -; mRNA. DR EMBL; AK314879; BAG37394.1; -; mRNA. DR EMBL; EF141836; ABK97430.1; -; Genomic_DNA. DR EMBL; AP001724; BAA95508.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09754.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09755.1; -; Genomic_DNA. DR EMBL; BC002511; AAH02511.1; -; mRNA. DR EMBL; BC015640; AAH15640.1; -; mRNA. DR CCDS; CCDS13641.1; -. [P16152-1] DR CCDS; CCDS68202.1; -. [P16152-2] DR PIR; A61271; RDHUCB. DR RefSeq; NP_001273718.1; NM_001286789.2. [P16152-2] DR RefSeq; NP_001748.1; NM_001757.4. [P16152-1] DR PDB; 1WMA; X-ray; 1.24 A; A=2-277. DR PDB; 2PFG; X-ray; 1.54 A; A=2-277. DR PDB; 3BHI; X-ray; 2.27 A; A=2-277. DR PDB; 3BHJ; X-ray; 1.77 A; A=2-277. DR PDB; 3BHM; X-ray; 1.80 A; A=2-277. DR PDB; 4Z3D; X-ray; 1.80 A; A/B/C/D=2-277. DR AlphaFoldDB; P16152; -. DR SMR; P16152; -. DR BioGRID; 107319; 189. DR DIP; DIP-33136N; -. DR FunCoup; P16152; 434. DR IntAct; P16152; 96. DR MINT; P16152; -. DR NDEx; IQUERY-CP-CBR1; 6 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000290349; -. DR BindingDB; P16152; -. DR ChEMBL; CHEMBL5586; -. DR DrugBank; DB03556; 2-(2-{2-[2-(2-{2-[2-(2-Ethoxy-Ethoxy)-Ethoxy]-Ethoxy}-Ethoxy)-Ethoxy]-Ethoxy}-Ethoxy)-Ethanol, Polyethyleneglycol Peg400. DR DrugBank; DB04463; 3-(4-Amino-1-Tert-Butyl-1h-Pyrazolo[3,4-D]Pyrimidin-3-Yl)Phenol. DR DrugBank; DB00414; Acetohexamide. DR DrugBank; DB06263; Amrubicin. DR DrugBank; DB11672; Curcumin. DR DrugBank; DB14635; Curcumin sulfate. DR DrugBank; DB00694; Daunorubicin. DR DrugBank; DB12161; Deutetrabenazine. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB01039; Fenofibrate. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB03394; Heptaethylene glycol. DR DrugBank; DB09212; Loxoprofen. DR DrugBank; DB01046; Lubiprostone. DR DrugBank; DB12206; N-6022. DR DrugBank; DB00776; Oxcarbazepine. DR DrugBank; DB04216; Quercetin. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB01698; Rutin. DR DrugBank; DB05197; Sofalcone. DR DrugBank; DB04844; Tetrabenazine. DR DrugCentral; P16152; -. DR GuidetoPHARMACOLOGY; 1383; -. DR GlyGen; P16152; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P16152; -. DR MetOSite; P16152; -. DR PhosphoSitePlus; P16152; -. DR SwissPalm; P16152; -. DR BioMuta; CBR1; -. DR DMDM; 118519; -. DR REPRODUCTION-2DPAGE; IPI00295386; -. DR CPTAC; CPTAC-329; -. DR CPTAC; CPTAC-330; -. DR jPOST; P16152; -. DR MassIVE; P16152; -. DR PaxDb; 9606-ENSP00000290349; -. DR PeptideAtlas; P16152; -. DR PRIDE; P16152; -. DR ProteomicsDB; 4051; -. DR ProteomicsDB; 53298; -. [P16152-1] DR Pumba; P16152; -. DR TopDownProteomics; P16152-1; -. [P16152-1] DR Antibodypedia; 8245; 502 antibodies from 39 providers. DR DNASU; 873; -. DR Ensembl; ENST00000290349.11; ENSP00000290349.6; ENSG00000159228.13. [P16152-1] DR Ensembl; ENST00000530908.5; ENSP00000434613.1; ENSG00000159228.13. [P16152-2] DR GeneID; 873; -. DR KEGG; hsa:873; -. DR MANE-Select; ENST00000290349.11; ENSP00000290349.6; NM_001757.4; NP_001748.1. DR UCSC; uc002yvb.3; human. [P16152-1] DR AGR; HGNC:1548; -. DR ClinPGx; PA26121; -. DR CTD; 873; -. DR DisGeNET; 873; -. DR GeneCards; CBR1; -. DR HGNC; HGNC:1548; CBR1. DR HPA; ENSG00000159228; Tissue enhanced (choroid plexus, intestine). DR MIM; 114830; gene. DR OpenTargets; ENSG00000159228; -. DR VEuPathDB; HostDB:ENSG00000159228; -. DR eggNOG; KOG1208; Eukaryota. DR GeneTree; ENSGT00510000046499; -. DR HOGENOM; CLU_010194_9_0_1; -. DR InParanoid; P16152; -. DR OMA; GAQTPVM; -. DR OrthoDB; 7289984at2759; -. DR PAN-GO; P16152; 1 GO annotation based on evolutionary models. DR PhylomeDB; P16152; -. DR BioCyc; MetaCyc:HS08378-MONOMER; -. DR BRENDA; 1.1.1.184; 2681. DR PathwayCommons; P16152; -. DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX). DR SABIO-RK; P16152; -. DR SignaLink; P16152; -. DR Agora; ENSG00000159228; -. DR BioGRID-ORCS; 873; 7 hits in 1165 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; CBR1; human. DR EvolutionaryTrace; P16152; -. DR GeneWiki; CBR1; -. DR GenomeRNAi; 873; -. DR Pharos; P16152; Tchem. DR PRO; PR:P16152; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P16152; protein. DR Bgee; ENSG00000159228; Expressed in jejunal mucosa and 194 other cell types or tissues. DR ExpressionAtlas; P16152; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB. DR GO; GO:0047021; F:15-hydroxyprostaglandin dehydrogenase (NADP+) activity; EXP:UniProtKB. DR GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; ISS:UniProtKB. DR GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; EXP:UniProtKB. DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:UniProtKB. DR GO; GO:0008753; F:NADPH dehydrogenase (quinone) activity; IEA:RHEA. DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB. DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IDA:UniProtKB. DR GO; GO:0050221; F:prostaglandin E2 9-reductase activity; EXP:UniProtKB. DR GO; GO:0160163; F:S-nitrosoglutathione reductase (NADPH) activity; EXP:UniProtKB. DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB. DR GO; GO:0008211; P:glucocorticoid metabolic process; IDA:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB. DR GO; GO:0046457; P:prostanoid biosynthetic process; TAS:Reactome. DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProtKB. DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB. DR CDD; cd05324; carb_red_PTCR-like_SDR_c; 1. DR FunFam; 3.40.50.720:FF:000164; Carbonyl reductase [NADPH] 1; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR045313; CBR1-like. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR020904; Sc_DH/Rdtase_CS. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR43963; CARBONYL REDUCTASE 1-RELATED; 1. DR PANTHER; PTHR43963:SF2; CARBONYL REDUCTASE [NADPH] 1; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR PRINTS; PR00080; SDRFAMILY. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00061; ADH_SHORT; 1. DR PDBsum; 1WMA; -. DR PDBsum; 2PFG; -. DR PDBsum; 3BHI; -. DR PDBsum; 3BHJ; -. DR PDBsum; 3BHM; -. DR PDBsum; 4Z3D; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase; KW Phosphoprotein; Proteomics identification; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..277 FT /note="Carbonyl reductase [NADPH] 1" FT /id="PRO_0000054602" FT ACT_SITE 194 FT /note="Proton acceptor" FT BINDING 10..34 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:15799708, FT ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18826943" FT BINDING 63..64 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:15799708, FT ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18826943" FT BINDING 90 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:15799708, FT ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18826943" FT BINDING 95..97 FT /ligand="glutathione" FT /ligand_id="ChEBI:CHEBI:57925" FT BINDING 106 FT /ligand="glutathione" FT /ligand_id="ChEBI:CHEBI:57925" FT BINDING 140 FT /ligand="substrate" FT BINDING 193..194 FT /ligand="glutathione" FT /ligand_id="ChEBI:CHEBI:57925" FT BINDING 194..198 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:15799708, FT ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18826943" FT BINDING 231..233 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:15799708, FT ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18826943" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P47727" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48758" FT MOD_RES 239 FT /note="N6-1-carboxyethyl lysine" FT /evidence="ECO:0000269|PubMed:8421682" FT VAR_SEQ 133..173 FT /note="GRVVNVSSIMSVRALKSCSPELQQKFRSETITEEELVGLMN -> ASCVLSA FT WSCLSQNPSGGKSKPLAWFTEMSIICRCLTLGPF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054796" FT VAR_SEQ 174..277 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054797" FT VARIANT 88 FT /note="V -> I (reduced affinity for NADPH and reduced FT activity towards daunorubicin and prostaglandin E2; FT dbSNP:rs1143663)" FT /evidence="ECO:0000269|PubMed:17344335, FT ECO:0000269|PubMed:18449627" FT /id="VAR_059053" FT VARIANT 131 FT /note="P -> S (in dbSNP:rs41557318)" FT /evidence="ECO:0000269|Ref.9" FT /id="VAR_031706" FT HELIX 4..6 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 7..12 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 16..28 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 29..39 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 40..52 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 58..61 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 67..81 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 82..89 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 103..111 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 112..117 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 118..125 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 126..128 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 129..138 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 141..148 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 152..159 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 165..180 FT /evidence="ECO:0007829|PDB:1WMA" FT TURN 184..188 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 193..215 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 222..227 FT /evidence="ECO:0007829|PDB:1WMA" FT TURN 234..236 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 244..247 FT /evidence="ECO:0007829|PDB:1WMA" FT HELIX 249..255 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 268..270 FT /evidence="ECO:0007829|PDB:1WMA" FT STRAND 273..275 FT /evidence="ECO:0007829|PDB:1WMA" SQ SEQUENCE 277 AA; 30375 MW; 51A5A495EB4F4EC3 CRC64; MSSGIHVALV TGGNKGIGLA IVRDLCRLFS GDVVLTARDV TRGQAAVQQL QAEGLSPRFH QLDIDDLQSI RALRDFLRKE YGGLDVLVNN AGIAFKVADP TPFHIQAEVT MKTNFFGTRD VCTELLPLIK PQGRVVNVSS IMSVRALKSC SPELQQKFRS ETITEEELVG LMNKFVEDTK KGVHQKEGWP SSAYGVTKIG VTVLSRIHAR KLSEQRKGDK ILLNACCPGW VRTDMAGPKA TKSPEEGAET PVYLALLPPD AEGPHGQFVS EKRVEQW //