CBR1_HUMAN
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 03-AUG-2022, entry version 225.
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:18449627, PubMed:15799708, PubMed:17912391,
CC PubMed:7005231, PubMed:1921984, PubMed:17344335, PubMed:18826943). 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:18826943, PubMed:17344335). 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 + H(+) + NADPH;
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 + H(+) + NADPH;
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=NADP(+) + prostaglandin F2alpha = H(+) + NADPH + prostaglandin
CC E2; 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=NADP(+) + prostaglandin E1 = 15-oxoprostaglandin E1 + H(+) +
CC NADPH; 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=H(+) + menadione + NADPH = 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=NADP(+) + prostaglandin D2 = 15-oxoprostaglandin D2 + H(+) +
CC NADPH; 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=NADP(+) + prostaglandin E2 = 15-oxoprostaglandin E2 + H(+) +
CC NADPH; 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=NADP(+) + prostaglandin F2alpha = 15-oxoprostaglandin F2alpha
CC + H(+) + NADPH; 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 + H(+) + NADPH = 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=H(+) + NADPH + S-nitrosoglutathione = NADP(+) + sulfinamide
CC glutathione; Xref=Rhea:RHEA:63500, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:145544,
CC ChEBI:CHEBI:145547; Evidence={ECO:0000269|PubMed:18826943};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisol + H(+) + NADPH = 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 + H(+) + NADPH = 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 -!- 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 -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cbr1/";
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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_001286789.1. [P16152-2]
DR RefSeq; NP_001748.1; NM_001757.3. [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 PDBsum; 1WMA; -.
DR PDBsum; 2PFG; -.
DR PDBsum; 3BHI; -.
DR PDBsum; 3BHJ; -.
DR PDBsum; 3BHM; -.
DR PDBsum; 4Z3D; -.
DR AlphaFoldDB; P16152; -.
DR SMR; P16152; -.
DR BioGRID; 107319; 129.
DR DIP; DIP-33136N; -.
DR IntAct; P16152; 50.
DR MINT; P16152; -.
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; 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; 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 UCD-2DPAGE; P16152; -.
DR CPTAC; CPTAC-329; -.
DR CPTAC; CPTAC-330; -.
DR EPD; P16152; -.
DR jPOST; P16152; -.
DR MassIVE; P16152; -.
DR MaxQB; P16152; -.
DR PaxDb; P16152; -.
DR PeptideAtlas; P16152; -.
DR PRIDE; P16152; -.
DR ProteomicsDB; 4051; -.
DR ProteomicsDB; 53298; -. [P16152-1]
DR TopDownProteomics; P16152-1; -. [P16152-1]
DR Antibodypedia; 8245; 490 antibodies from 37 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 CTD; 873; -.
DR DisGeNET; 873; -.
DR GeneCards; CBR1; -.
DR HGNC; HGNC:1548; CBR1.
DR HPA; ENSG00000159228; Tissue enhanced (intestine).
DR MIM; 114830; gene.
DR neXtProt; NX_P16152; -.
DR OpenTargets; ENSG00000159228; -.
DR PharmGKB; PA26121; -.
DR VEuPathDB; HostDB:ENSG00000159228; -.
DR eggNOG; KOG1208; Eukaryota.
DR GeneTree; ENSGT00510000046499; -.
DR HOGENOM; CLU_010194_9_0_1; -.
DR InParanoid; P16152; -.
DR OMA; LALQYPK; -.
DR OrthoDB; 1259665at2759; -.
DR PhylomeDB; P16152; -.
DR TreeFam; TF329359; -.
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 BioGRID-ORCS; 873; 5 hits in 1084 CRISPR screens.
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 192 other tissues.
DR ExpressionAtlas; P16152; baseline and differential.
DR Genevisible; P16152; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; ISS:UniProtKB.
DR GO; GO:0047020; F:15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0008106; F:alcohol dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome.
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: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 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 Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Lipid metabolism; NADP; Oxidoreductase;
KW Phosphoprotein; 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 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..114
FT /evidence="ECO:0007829|PDB:1WMA"
FT HELIX 116..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
