Full text data of CBR1
CBR1
(CBR, CRN)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Carbonyl reductase [NADPH] 1; 1.1.1.184 (15-hydroxyprostaglandin dehydrogenase [NADP(+)]; 1.1.1.197; NADPH-dependent carbonyl reductase 1; Prostaglandin 9-ketoreductase; Prostaglandin-E(2) 9-reductase; 1.1.1.189)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Carbonyl reductase [NADPH] 1; 1.1.1.184 (15-hydroxyprostaglandin dehydrogenase [NADP(+)]; 1.1.1.197; NADPH-dependent carbonyl reductase 1; Prostaglandin 9-ketoreductase; Prostaglandin-E(2) 9-reductase; 1.1.1.189)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00295386
IPI00295386 Carbonyl reductase [NADPH] 1 Carbonyl reductase [NADPH] 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00295386 Carbonyl reductase [NADPH] 1 Carbonyl reductase [NADPH] 1 membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P16152
ID CBR1_HUMAN Reviewed; 277 AA.
AC P16152; B2RBZ7; Q3LHW8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Carbonyl reductase [NADPH] 1;
DE EC=1.1.1.184;
DE AltName: Full=15-hydroxyprostaglandin dehydrogenase [NADP(+)];
DE EC=1.1.1.197;
DE AltName: Full=NADPH-dependent carbonyl reductase 1;
DE AltName: Full=Prostaglandin 9-ketoreductase;
DE AltName: Full=Prostaglandin-E(2) 9-reductase;
DE EC=1.1.1.189;
GN Name=CBR1; Synonyms=CBR, CRN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Placenta;
RX PubMed=3141401;
RA Wermuth B., Bohren K.M., Heinemann G., von Wartburg J.-P.,
RA Gabbay K.H.;
RT "Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and
RT amino acid sequence of the encoded protein.";
RL J. Biol. Chem. 263:16185-16188(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], 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.,
RA Doroshow J., Felsted R.L., Mohandas T., Bachur N.R.;
RT "Induction of a human carbonyl reductase gene located on chromosome
RT 21.";
RL Biochim. Biophys. Acta 1048:149-155(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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
RT gene with daunorubicin reductase activity.";
RL Mol. Pharmacol. 40:502-507(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9740676; DOI=10.1006/geno.1998.5380;
RA Watanabe K., Sugawara C., Ono A., Fukuzumi Y., Itakura S.,
RA Yamazaki M., 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].
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].
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., 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].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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], 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.,
RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP PARTIAL PROTEIN SEQUENCE, AND N6-1-CARBOXYETHYLATION 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 ENZYME REGULATION, AND FUNCTION.
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 2-276 IN COMPLEX WITH THE
RP SYNTHETIC INHIBITOR HYDROXY-PP AND NADP, MASS SPECTROMETRY, PARTIAL
RP PROTEIN SEQUENCE, AND FUNCTION.
RX PubMed=15799708; DOI=10.1371/journal.pbio.0030128;
RA Tanaka M., Bateman R., Rauh D., Vaisberg E., Ramachandani S.,
RA Zhang C., Hansen K.C., Burlingame A.L., Trautman J.K., Shokat K.M.,
RA 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 [18]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP
RP AND FORMALDEHYDE-GLUTATHIONE ADDUCT, AND FUNCTION.
RX PubMed=17912391; DOI=10.1039/b707602a;
RA Bateman R., Rauh D., Shokat K.M.;
RT "Glutathione traps formaldehyde by formation of a
RT bicyclo[4.4.1]undecane adduct.";
RL Org. Biomol. Chem. 5:3363-3367(2007).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP,
RP SUBSTRATE ANALOGS, FUNCTION, AND BIOPHYSICOCHEMICAL 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 [20]
RP VARIANT ILE-88, CHARACTERIZATION OF VARIANT ILE-88, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ENZYME REGULATION.
RX PubMed=17344335; DOI=10.1124/dmd.107.014779;
RA Gonzalez-Covarrubias V., Ghosh D., Lakhman S.S., Pendyala L.,
RA 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
CC specificity. Catalyzes the reduction of a wide variety of carbonyl
CC compounds including quinones, prostaglandins, menadione, plus
CC various xenobiotics. Catalyzes the reduction of the antitumor
CC anthracyclines doxorubicin and daunorubicin to the cardiotoxic
CC compounds doxorubicinol and daunorubicinol. Can convert
CC prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione,
CC which explains its higher affinity for glutathione-conjugated
CC substrates. Catalyzes the reduction of S-nitrosoglutathione.
CC -!- CATALYTIC ACTIVITY: R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.
CC -!- CATALYTIC ACTIVITY: (5Z,13E)-(15S)-9-alpha,11-alpha,15-
CC trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-11-
CC alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH.
CC -!- CATALYTIC ACTIVITY: (13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-
CC 13-enoate + NADP(+) = (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-
CC enoate + NADPH.
CC -!- ENZYME REGULATION: Inhibited by quercetin, rutenin and its
CC derivatives.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for S-nitrosoglutathione;
CC KM=22 uM for menadione;
CC KM=309 uM for prostaglandin E2;
CC KM=173 uM for daunorubicin;
CC KM=247 uM for NADPH;
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases
CC (SDR) family.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cbr1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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; AK314879; BAG37394.1; -; mRNA.
DR EMBL; EF141836; ABK97430.1; -; Genomic_DNA.
DR EMBL; AP001724; BAA95508.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09755.1; -; Genomic_DNA.
DR EMBL; BC002511; AAH02511.1; -; mRNA.
DR EMBL; BC015640; AAH15640.1; -; mRNA.
DR PIR; A61271; RDHUCB.
DR RefSeq; NP_001748.1; NM_001757.3.
DR UniGene; Hs.606200; -.
DR UniGene; Hs.88778; -.
DR PDB; 1WMA; X-ray; 1.24 A; A=2-276.
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 PDBsum; 1WMA; -.
DR PDBsum; 2PFG; -.
DR PDBsum; 3BHI; -.
DR PDBsum; 3BHJ; -.
DR PDBsum; 3BHM; -.
DR ProteinModelPortal; P16152; -.
DR SMR; P16152; 3-277.
DR DIP; DIP-33136N; -.
DR IntAct; P16152; 9.
DR MINT; MINT-1418935; -.
DR STRING; 9606.ENSP00000290349; -.
DR BindingDB; P16152; -.
DR ChEMBL; CHEMBL5586; -.
DR DrugBank; DB00414; Acetohexamide.
DR DrugBank; DB01046; Lubiprostone.
DR PhosphoSite; P16152; -.
DR DMDM; 118519; -.
DR REPRODUCTION-2DPAGE; IPI00295386; -.
DR UCD-2DPAGE; P16152; -.
DR PaxDb; P16152; -.
DR PeptideAtlas; P16152; -.
DR PRIDE; P16152; -.
DR DNASU; 873; -.
DR Ensembl; ENST00000290349; ENSP00000290349; ENSG00000159228.
DR GeneID; 873; -.
DR KEGG; hsa:873; -.
DR UCSC; uc002yvb.1; human.
DR CTD; 873; -.
DR GeneCards; GC21P037442; -.
DR HGNC; HGNC:1548; CBR1.
DR HPA; HPA018433; -.
DR MIM; 114830; gene.
DR neXtProt; NX_P16152; -.
DR PharmGKB; PA26121; -.
DR eggNOG; COG1028; -.
DR HOVERGEN; HBG001909; -.
DR InParanoid; P16152; -.
DR KO; K00079; -.
DR OMA; VIGVIRV; -.
DR PhylomeDB; P16152; -.
DR BRENDA; 1.1.1.184; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P16152; -.
DR EvolutionaryTrace; P16152; -.
DR GeneWiki; CBR1; -.
DR GenomeRNAi; 873; -.
DR NextBio; 3634; -.
DR PRO; PR:P16152; -.
DR ArrayExpress; P16152; -.
DR Bgee; P16152; -.
DR CleanEx; HS_CBR1; -.
DR Genevestigator; P16152; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0047021; F:15-hydroxyprostaglandin dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR GO; GO:0050221; F:prostaglandin-E2 9-reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome.
DR GO; GO:0017144; P:drug metabolic process; IDA:UniProtKB.
DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR002198; DH_sc/Rdtase_SDR.
DR InterPro; IPR002347; Glc/ribitol_DH.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 277 Carbonyl reductase [NADPH] 1.
FT /FTId=PRO_0000054602.
FT NP_BIND 10 34 NADP.
FT NP_BIND 63 64 NADP.
FT NP_BIND 194 198 NADP.
FT NP_BIND 231 233 NADP.
FT REGION 95 97 Glutathione binding.
FT REGION 193 194 Glutathione binding.
FT ACT_SITE 194 194 Proton acceptor.
FT BINDING 90 90 NADP; via carbonyl oxygen.
FT BINDING 106 106 Glutathione.
FT BINDING 140 140 Substrate.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 239 239 N6-1-carboxyethyl lysine.
FT VARIANT 88 88 V -> I (reduced affinity for NADPH and
FT reduced activity towards daunorubicin and
FT prostaglandin E2; dbSNP:rs1143663).
FT /FTId=VAR_059053.
FT VARIANT 131 131 P -> S (in dbSNP:rs41557318).
FT /FTId=VAR_031706.
FT STRAND 7 12
FT HELIX 16 28
FT STRAND 29 39
FT HELIX 40 52
FT STRAND 58 61
FT HELIX 67 81
FT STRAND 82 89
FT HELIX 103 114
FT HELIX 116 125
FT HELIX 126 128
FT STRAND 129 138
FT HELIX 141 148
FT HELIX 152 159
FT HELIX 165 180
FT TURN 184 188
FT HELIX 193 215
FT STRAND 222 227
FT TURN 234 236
FT HELIX 244 247
FT HELIX 249 255
FT STRAND 268 270
FT STRAND 273 275
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
//
ID CBR1_HUMAN Reviewed; 277 AA.
AC P16152; B2RBZ7; Q3LHW8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Carbonyl reductase [NADPH] 1;
DE EC=1.1.1.184;
DE AltName: Full=15-hydroxyprostaglandin dehydrogenase [NADP(+)];
DE EC=1.1.1.197;
DE AltName: Full=NADPH-dependent carbonyl reductase 1;
DE AltName: Full=Prostaglandin 9-ketoreductase;
DE AltName: Full=Prostaglandin-E(2) 9-reductase;
DE EC=1.1.1.189;
GN Name=CBR1; Synonyms=CBR, CRN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Placenta;
RX PubMed=3141401;
RA Wermuth B., Bohren K.M., Heinemann G., von Wartburg J.-P.,
RA Gabbay K.H.;
RT "Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and
RT amino acid sequence of the encoded protein.";
RL J. Biol. Chem. 263:16185-16188(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], 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.,
RA Doroshow J., Felsted R.L., Mohandas T., Bachur N.R.;
RT "Induction of a human carbonyl reductase gene located on chromosome
RT 21.";
RL Biochim. Biophys. Acta 1048:149-155(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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
RT gene with daunorubicin reductase activity.";
RL Mol. Pharmacol. 40:502-507(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9740676; DOI=10.1006/geno.1998.5380;
RA Watanabe K., Sugawara C., Ono A., Fukuzumi Y., Itakura S.,
RA Yamazaki M., 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].
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].
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
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., 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].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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], 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.,
RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y.,
RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K.,
RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D.,
RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W.,
RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S.,
RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E.,
RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P.,
RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H.,
RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E.,
RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP PARTIAL PROTEIN SEQUENCE, AND N6-1-CARBOXYETHYLATION 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 ENZYME REGULATION, AND FUNCTION.
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 2-276 IN COMPLEX WITH THE
RP SYNTHETIC INHIBITOR HYDROXY-PP AND NADP, MASS SPECTROMETRY, PARTIAL
RP PROTEIN SEQUENCE, AND FUNCTION.
RX PubMed=15799708; DOI=10.1371/journal.pbio.0030128;
RA Tanaka M., Bateman R., Rauh D., Vaisberg E., Ramachandani S.,
RA Zhang C., Hansen K.C., Burlingame A.L., Trautman J.K., Shokat K.M.,
RA 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 [18]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP
RP AND FORMALDEHYDE-GLUTATHIONE ADDUCT, AND FUNCTION.
RX PubMed=17912391; DOI=10.1039/b707602a;
RA Bateman R., Rauh D., Shokat K.M.;
RT "Glutathione traps formaldehyde by formation of a
RT bicyclo[4.4.1]undecane adduct.";
RL Org. Biomol. Chem. 5:3363-3367(2007).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP,
RP SUBSTRATE ANALOGS, FUNCTION, AND BIOPHYSICOCHEMICAL 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 [20]
RP VARIANT ILE-88, CHARACTERIZATION OF VARIANT ILE-88, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ENZYME REGULATION.
RX PubMed=17344335; DOI=10.1124/dmd.107.014779;
RA Gonzalez-Covarrubias V., Ghosh D., Lakhman S.S., Pendyala L.,
RA 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
CC specificity. Catalyzes the reduction of a wide variety of carbonyl
CC compounds including quinones, prostaglandins, menadione, plus
CC various xenobiotics. Catalyzes the reduction of the antitumor
CC anthracyclines doxorubicin and daunorubicin to the cardiotoxic
CC compounds doxorubicinol and daunorubicinol. Can convert
CC prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione,
CC which explains its higher affinity for glutathione-conjugated
CC substrates. Catalyzes the reduction of S-nitrosoglutathione.
CC -!- CATALYTIC ACTIVITY: R-CHOH-R' + NADP(+) = R-CO-R' + NADPH.
CC -!- CATALYTIC ACTIVITY: (5Z,13E)-(15S)-9-alpha,11-alpha,15-
CC trihydroxyprosta-5,13-dienoate + NADP(+) = (5Z,13E)-(15S)-11-
CC alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH.
CC -!- CATALYTIC ACTIVITY: (13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-
CC 13-enoate + NADP(+) = (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-
CC enoate + NADPH.
CC -!- ENZYME REGULATION: Inhibited by quercetin, rutenin and its
CC derivatives.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=30 uM for S-nitrosoglutathione;
CC KM=22 uM for menadione;
CC KM=309 uM for prostaglandin E2;
CC KM=173 uM for daunorubicin;
CC KM=247 uM for NADPH;
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases
CC (SDR) family.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cbr1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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; AK314879; BAG37394.1; -; mRNA.
DR EMBL; EF141836; ABK97430.1; -; Genomic_DNA.
DR EMBL; AP001724; BAA95508.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09755.1; -; Genomic_DNA.
DR EMBL; BC002511; AAH02511.1; -; mRNA.
DR EMBL; BC015640; AAH15640.1; -; mRNA.
DR PIR; A61271; RDHUCB.
DR RefSeq; NP_001748.1; NM_001757.3.
DR UniGene; Hs.606200; -.
DR UniGene; Hs.88778; -.
DR PDB; 1WMA; X-ray; 1.24 A; A=2-276.
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 PDBsum; 1WMA; -.
DR PDBsum; 2PFG; -.
DR PDBsum; 3BHI; -.
DR PDBsum; 3BHJ; -.
DR PDBsum; 3BHM; -.
DR ProteinModelPortal; P16152; -.
DR SMR; P16152; 3-277.
DR DIP; DIP-33136N; -.
DR IntAct; P16152; 9.
DR MINT; MINT-1418935; -.
DR STRING; 9606.ENSP00000290349; -.
DR BindingDB; P16152; -.
DR ChEMBL; CHEMBL5586; -.
DR DrugBank; DB00414; Acetohexamide.
DR DrugBank; DB01046; Lubiprostone.
DR PhosphoSite; P16152; -.
DR DMDM; 118519; -.
DR REPRODUCTION-2DPAGE; IPI00295386; -.
DR UCD-2DPAGE; P16152; -.
DR PaxDb; P16152; -.
DR PeptideAtlas; P16152; -.
DR PRIDE; P16152; -.
DR DNASU; 873; -.
DR Ensembl; ENST00000290349; ENSP00000290349; ENSG00000159228.
DR GeneID; 873; -.
DR KEGG; hsa:873; -.
DR UCSC; uc002yvb.1; human.
DR CTD; 873; -.
DR GeneCards; GC21P037442; -.
DR HGNC; HGNC:1548; CBR1.
DR HPA; HPA018433; -.
DR MIM; 114830; gene.
DR neXtProt; NX_P16152; -.
DR PharmGKB; PA26121; -.
DR eggNOG; COG1028; -.
DR HOVERGEN; HBG001909; -.
DR InParanoid; P16152; -.
DR KO; K00079; -.
DR OMA; VIGVIRV; -.
DR PhylomeDB; P16152; -.
DR BRENDA; 1.1.1.184; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P16152; -.
DR EvolutionaryTrace; P16152; -.
DR GeneWiki; CBR1; -.
DR GenomeRNAi; 873; -.
DR NextBio; 3634; -.
DR PRO; PR:P16152; -.
DR ArrayExpress; P16152; -.
DR Bgee; P16152; -.
DR CleanEx; HS_CBR1; -.
DR Genevestigator; P16152; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0047021; F:15-hydroxyprostaglandin dehydrogenase (NADP+) activity; IEA:UniProtKB-EC.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:UniProtKB.
DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; IDA:UniProtKB.
DR GO; GO:0050221; F:prostaglandin-E2 9-reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome.
DR GO; GO:0017144; P:drug metabolic process; IDA:UniProtKB.
DR GO; GO:0042373; P:vitamin K metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR002198; DH_sc/Rdtase_SDR.
DR InterPro; IPR002347; Glc/ribitol_DH.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; NADP; Oxidoreductase; Polymorphism;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 277 Carbonyl reductase [NADPH] 1.
FT /FTId=PRO_0000054602.
FT NP_BIND 10 34 NADP.
FT NP_BIND 63 64 NADP.
FT NP_BIND 194 198 NADP.
FT NP_BIND 231 233 NADP.
FT REGION 95 97 Glutathione binding.
FT REGION 193 194 Glutathione binding.
FT ACT_SITE 194 194 Proton acceptor.
FT BINDING 90 90 NADP; via carbonyl oxygen.
FT BINDING 106 106 Glutathione.
FT BINDING 140 140 Substrate.
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 239 239 N6-1-carboxyethyl lysine.
FT VARIANT 88 88 V -> I (reduced affinity for NADPH and
FT reduced activity towards daunorubicin and
FT prostaglandin E2; dbSNP:rs1143663).
FT /FTId=VAR_059053.
FT VARIANT 131 131 P -> S (in dbSNP:rs41557318).
FT /FTId=VAR_031706.
FT STRAND 7 12
FT HELIX 16 28
FT STRAND 29 39
FT HELIX 40 52
FT STRAND 58 61
FT HELIX 67 81
FT STRAND 82 89
FT HELIX 103 114
FT HELIX 116 125
FT HELIX 126 128
FT STRAND 129 138
FT HELIX 141 148
FT HELIX 152 159
FT HELIX 165 180
FT TURN 184 188
FT HELIX 193 215
FT STRAND 222 227
FT TURN 234 236
FT HELIX 244 247
FT HELIX 249 255
FT STRAND 268 270
FT STRAND 273 275
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
//
MIM
114830
*RECORD*
*FIELD* NO
114830
*FIELD* TI
*114830 CARBONYL REDUCTASE 1; CBR1
;;CARBONYL REDUCTASE; CBR
*FIELD* TX
DESCRIPTION
read more
Carbonyl reductase (EC 1.1.1.184) is 1 of several monomeric,
NADPH-dependent oxidoreductases having wide specificity for carbonyl
compounds that are generally referred to as aldo-keto reductases. Others
include aldehyde reductase (EC 1.1.1.2; 103830) and aldose reductase (EC
1.1.1.21; 103880).
CLONING
Wermuth et al. (1988) isolated and characterized a cDNA complementary to
carbonyl reductase mRNA from a human placenta cDNA library. The cDNA
contained an open reading frame encoding a protein comprised of 277
amino acids with a molecular weight of 30,375. Comparison of the
predicted protein sequence with the primary structures of other
aldo-keto reductases showed no significant homologies. A possible
homology, on the other hand, was found between carbonyl reductase and
'short' subunit alcohol/polyol dehydrogenases. The enzyme is widely
distributed in human tissues and also occurs in other mammalian and
nonmammalian species.
In a carbonyl reductase cDNA cloned from a breast cancer cell line,
Forrest et al. (1990) demonstrated 1,219 basepairs. Southern analysis of
genomic DNA digested with several restriction enzymes and analyzed by
hybridization with a labeled cDNA probe indicated that carbonyl
reductase is probably coded by a single gene and does not belong to a
family of structurally similar enzymes. Carbonyl reductase mRNA was
induced 3- or 4-fold in 24 hours with BHA, beta-naphthoflavone, or Sudan
1.
MAPPING
By Southern blot analysis of 17 mouse/human somatic cell hybrids,
Forrest et al. (1990) showed that the CBR gene is located on chromosome
21.
Avramopoulos et al. (1992) confirmed assignment to chromosome 21 by
genetic linkage mapping using a DNA polymorphism from the 3-prime
untranslated region of the CBR gene. They demonstrated, furthermore,
that the gene lies between the interferon-alpha receptor gene (107450)
and D21S55, being about 3.4 and 7.2 cM, respectively, from the 2
flanking loci. The findings placed CBR in the telomeric band 21q22.3.
By high-resolution fluorescence in situ hybridization, Lemieux et al.
(1993) mapped the CBR gene to 21q22.12, very close to the SOD1 locus at
position 21q22.11. CBR displayed gene dosage effects in trisomy 21 human
lymphoblasts at both the DNA and the mRNA levels. With increasing
chromosome 21 ploidy, lymphoblasts also showed increased aldo-keto
reductase activity and increased quinone reductase activity. Both of
these activities have been shown to be associated with carbonyl
reductase. The location of CBR near SOD1 and the increased enzyme
activity and potential for free radical modulation in trisomy 21 cells
implicate CBR as a candidate for contributing to the pathology of Down
syndrome.
Wei et al. (1996) mapped the mouse Cbr1 gene to distal chromosome 16, as
had others. They identified a second carbonyl reductase gene in mouse
(Cbr2) and found that it mapped to distal chromosome 11.
GENE STRUCTURE
By sequence analysis of human chromosome region 21q22.2, Watanabe et al.
(1998) determined that the CBR1 gene contains 3 exons and spans 3.3 kb.
They identified a related gene, CBR3 (603608), 62 kb telomeric to CBR1.
GENE FUNCTION
Carbonyl reductase catalyzes the reduction of a great variety of
carbonyl compounds, e.g., quinones derived from polycyclic aromatic
hydrocarbons, 9-ketoprostaglandins, and the antitumor anthracycline
antibiotics daunorubicin and doxorubicin (Wermuth et al., 1988).
*FIELD* RF
1. Avramopoulos, D.; Cox, T.; Forrest, G. L.; Chakravarti, A.; Antonarakis,
S. E.: Linkage mapping of the carbonyl reductase (CBR) gene on human
chromosome 21 using a DNA polymorphism in the 3-prime untranslated
region. Genomics 13: 447-448, 1992.
2. Forrest, G. L.; Akman, S.; Krutzik, S.; Paxton, R. J.; Sparkes,
R. S.; Doroshow, J.; Felsted, R. L.; Glover, C. J.; Mohandas, T.;
Bachur, N. R.: Induction of a human carbonyl reductase gene located
on chromosome 21. Biochim. Biophys. Acta 1048: 149-155, 1990.
3. Lemieux, N.; Malfoy, B.; Forrest, G. L.: Human carbonyl reductase
(CBR) localized to band 21q22.1 by high-resolution fluorescence in
situ hybridization displays gene dosage effects in trisomy 21 cells. Genomics 15:
169-172, 1993.
4. Watanabe, K.; Sugawara, C.; Ono, A.; Fukuzumi, Y.; Itakura, S.;
Yamazaki, M.; Tashiro, H.; Osoegawa, K.; Soeda, E.; Nomura, T.: Mapping
of a novel human carbonyl reductase, CBR3, and ribosomal pseudogenes
to human chromosome 21q22.2. Genomics 52: 95-100, 1998.
5. Wei, J.; Dlouhy, S. R.; Hara, A.; Ghetti, B.; Hodes, M. E.: Cloning
a cDNA for carbonyl reductase (Cbr) from mouse cerebellum: murine
genes that express Cbr map to chromosomes 16 and 11. Genomics 34:
147-148, 1996.
6. Wermuth, B.; Bohren, K. M.; Heinemann, G.; von Wartburg, J.-P.;
Gabbay, K. H.: Human carbonyl reductase: nucleotide sequence analysis
of a cDNA and amino acid sequence of the encoded protein. J. Biol.
Chem. 263: 16185-16188, 1988.
*FIELD* CN
Rebekah S. Rasooly - updated: 3/4/1999
*FIELD* CD
Victor A. McKusick: 12/20/1988
*FIELD* ED
carol: 07/09/2009
joanna: 2/2/2009
mgross: 3/4/1999
alopez: 8/25/1998
terry: 6/5/1996
terry: 6/3/1996
carol: 2/11/1993
carol: 6/26/1992
carol: 6/24/1992
supermim: 3/16/1992
carol: 2/20/1991
carol: 10/10/1990
*RECORD*
*FIELD* NO
114830
*FIELD* TI
*114830 CARBONYL REDUCTASE 1; CBR1
;;CARBONYL REDUCTASE; CBR
*FIELD* TX
DESCRIPTION
read more
Carbonyl reductase (EC 1.1.1.184) is 1 of several monomeric,
NADPH-dependent oxidoreductases having wide specificity for carbonyl
compounds that are generally referred to as aldo-keto reductases. Others
include aldehyde reductase (EC 1.1.1.2; 103830) and aldose reductase (EC
1.1.1.21; 103880).
CLONING
Wermuth et al. (1988) isolated and characterized a cDNA complementary to
carbonyl reductase mRNA from a human placenta cDNA library. The cDNA
contained an open reading frame encoding a protein comprised of 277
amino acids with a molecular weight of 30,375. Comparison of the
predicted protein sequence with the primary structures of other
aldo-keto reductases showed no significant homologies. A possible
homology, on the other hand, was found between carbonyl reductase and
'short' subunit alcohol/polyol dehydrogenases. The enzyme is widely
distributed in human tissues and also occurs in other mammalian and
nonmammalian species.
In a carbonyl reductase cDNA cloned from a breast cancer cell line,
Forrest et al. (1990) demonstrated 1,219 basepairs. Southern analysis of
genomic DNA digested with several restriction enzymes and analyzed by
hybridization with a labeled cDNA probe indicated that carbonyl
reductase is probably coded by a single gene and does not belong to a
family of structurally similar enzymes. Carbonyl reductase mRNA was
induced 3- or 4-fold in 24 hours with BHA, beta-naphthoflavone, or Sudan
1.
MAPPING
By Southern blot analysis of 17 mouse/human somatic cell hybrids,
Forrest et al. (1990) showed that the CBR gene is located on chromosome
21.
Avramopoulos et al. (1992) confirmed assignment to chromosome 21 by
genetic linkage mapping using a DNA polymorphism from the 3-prime
untranslated region of the CBR gene. They demonstrated, furthermore,
that the gene lies between the interferon-alpha receptor gene (107450)
and D21S55, being about 3.4 and 7.2 cM, respectively, from the 2
flanking loci. The findings placed CBR in the telomeric band 21q22.3.
By high-resolution fluorescence in situ hybridization, Lemieux et al.
(1993) mapped the CBR gene to 21q22.12, very close to the SOD1 locus at
position 21q22.11. CBR displayed gene dosage effects in trisomy 21 human
lymphoblasts at both the DNA and the mRNA levels. With increasing
chromosome 21 ploidy, lymphoblasts also showed increased aldo-keto
reductase activity and increased quinone reductase activity. Both of
these activities have been shown to be associated with carbonyl
reductase. The location of CBR near SOD1 and the increased enzyme
activity and potential for free radical modulation in trisomy 21 cells
implicate CBR as a candidate for contributing to the pathology of Down
syndrome.
Wei et al. (1996) mapped the mouse Cbr1 gene to distal chromosome 16, as
had others. They identified a second carbonyl reductase gene in mouse
(Cbr2) and found that it mapped to distal chromosome 11.
GENE STRUCTURE
By sequence analysis of human chromosome region 21q22.2, Watanabe et al.
(1998) determined that the CBR1 gene contains 3 exons and spans 3.3 kb.
They identified a related gene, CBR3 (603608), 62 kb telomeric to CBR1.
GENE FUNCTION
Carbonyl reductase catalyzes the reduction of a great variety of
carbonyl compounds, e.g., quinones derived from polycyclic aromatic
hydrocarbons, 9-ketoprostaglandins, and the antitumor anthracycline
antibiotics daunorubicin and doxorubicin (Wermuth et al., 1988).
*FIELD* RF
1. Avramopoulos, D.; Cox, T.; Forrest, G. L.; Chakravarti, A.; Antonarakis,
S. E.: Linkage mapping of the carbonyl reductase (CBR) gene on human
chromosome 21 using a DNA polymorphism in the 3-prime untranslated
region. Genomics 13: 447-448, 1992.
2. Forrest, G. L.; Akman, S.; Krutzik, S.; Paxton, R. J.; Sparkes,
R. S.; Doroshow, J.; Felsted, R. L.; Glover, C. J.; Mohandas, T.;
Bachur, N. R.: Induction of a human carbonyl reductase gene located
on chromosome 21. Biochim. Biophys. Acta 1048: 149-155, 1990.
3. Lemieux, N.; Malfoy, B.; Forrest, G. L.: Human carbonyl reductase
(CBR) localized to band 21q22.1 by high-resolution fluorescence in
situ hybridization displays gene dosage effects in trisomy 21 cells. Genomics 15:
169-172, 1993.
4. Watanabe, K.; Sugawara, C.; Ono, A.; Fukuzumi, Y.; Itakura, S.;
Yamazaki, M.; Tashiro, H.; Osoegawa, K.; Soeda, E.; Nomura, T.: Mapping
of a novel human carbonyl reductase, CBR3, and ribosomal pseudogenes
to human chromosome 21q22.2. Genomics 52: 95-100, 1998.
5. Wei, J.; Dlouhy, S. R.; Hara, A.; Ghetti, B.; Hodes, M. E.: Cloning
a cDNA for carbonyl reductase (Cbr) from mouse cerebellum: murine
genes that express Cbr map to chromosomes 16 and 11. Genomics 34:
147-148, 1996.
6. Wermuth, B.; Bohren, K. M.; Heinemann, G.; von Wartburg, J.-P.;
Gabbay, K. H.: Human carbonyl reductase: nucleotide sequence analysis
of a cDNA and amino acid sequence of the encoded protein. J. Biol.
Chem. 263: 16185-16188, 1988.
*FIELD* CN
Rebekah S. Rasooly - updated: 3/4/1999
*FIELD* CD
Victor A. McKusick: 12/20/1988
*FIELD* ED
carol: 07/09/2009
joanna: 2/2/2009
mgross: 3/4/1999
alopez: 8/25/1998
terry: 6/5/1996
terry: 6/3/1996
carol: 2/11/1993
carol: 6/26/1992
carol: 6/24/1992
supermim: 3/16/1992
carol: 2/20/1991
carol: 10/10/1990