CBR1_RAT
ID CBR1_RAT Reviewed; 277 AA.
AC P47727; O08558; Q3KR58;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Carbonyl reductase [NADPH] 1 {ECO:0000305};
DE EC=1.1.1.184 {ECO:0000250|UniProtKB:P16152};
DE AltName: Full=15-hydroxyprostaglandin dehydrogenase [NADP(+)];
DE EC=1.1.1.196 {ECO:0000250|UniProtKB:Q28960};
DE EC=1.1.1.197 {ECO:0000250|UniProtKB:P16152};
DE AltName: Full=20-beta-hydroxysteroid dehydrogenase {ECO:0000250|UniProtKB:Q28960};
DE AltName: Full=Alcohol dehydrogenase [NAD(P)+] CBR1;
DE EC=1.1.1.71 {ECO:0000250|UniProtKB:P16152};
DE AltName: Full=NADPH-dependent carbonyl reductase 1;
DE AltName: Full=Prostaglandin 9-ketoreductase {ECO:0000250|UniProtKB:Q28960};
DE Short=PG-9-KR {ECO:0000250|UniProtKB:Q28960};
DE AltName: Full=Prostaglandin-E(2) 9-reductase {ECO:0000250|UniProtKB:Q28960};
DE EC=1.1.1.189 {ECO:0000250|UniProtKB:Q28960};
GN Name=Cbr1 {ECO:0000312|RGD:2286}; Synonyms=Cbr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=7705364; DOI=10.1111/j.1432-1033.1995.tb20286.x;
RA Wermuth B., Maeder-Heinemann G., Ernst E.;
RT "Cloning and expression of carbonyl reductase from rat testis.";
RL Eur. J. Biochem. 228:473-479(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9015353; DOI=10.1006/bbrc.1996.5995;
RA Aoki H., Okada T., Mizutani T., Numata Y., Minegishi T., Miyamoto K.;
RT "Identification of two closely related genes, inducible and noninducible
RT carbonyl reductases in the rat ovary.";
RL Biochem. Biophys. Res. Commun. 230:518-523(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [4]
RP PROTEIN SEQUENCE OF 6-14; 17-24 AND 59-71, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus, and Spinal cord;
RA Lubec G., Diao W., Afjehi-Sadat L., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP PROTEIN SEQUENCE OF 104-138, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8198567; DOI=10.1006/bbrc.1994.1681;
RA Toft E., Soederstroem M., Ahlberg M.B., DePierre J.W.;
RT "A novel 34 kDa glutathione-binding protein in mature rat ovary.";
RL Biochem. Biophys. Res. Commun. 201:149-154(1994).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 xenobiotics
CC (PubMed:8198567, PubMed:7705364). Catalyzes the reduction of the
CC antitumor anthracyclines doxorubicin and daunorubicin to the
CC cardiotoxic compounds doxorubicinol and daunorubicinol (By similarity).
CC Can convert prostaglandin E to prostaglandin F2-alpha (By similarity).
CC Can bind glutathione, which explains its higher affinity for
CC glutathione-conjugated substrates. Catalyzes the reduction of S-
CC nitrosoglutathione. In addition, participates in the glucocorticoid
CC metabolism by catalyzing the NADPH-dependent cortisol/corticosterone
CC into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-
CC DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue (By
CC similarity). {ECO:0000250|UniProtKB:P16152,
CC ECO:0000250|UniProtKB:Q28960, ECO:0000269|PubMed:7705364,
CC ECO:0000269|PubMed:8198567}.
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:0000250|UniProtKB:P16152};
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:0000250|UniProtKB:Q28960};
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:0000250|UniProtKB:P16152};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11637;
CC Evidence={ECO:0000250|UniProtKB:P16152};
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:7705364, ECO:0000269|PubMed:8198567};
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:0000250|UniProtKB:P16152};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63505;
CC Evidence={ECO:0000250|UniProtKB:P16152};
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:0000250|UniProtKB:Q28960};
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:0000250|UniProtKB:P16152};
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:0000250|UniProtKB:P16152};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70216;
CC Evidence={ECO:0000250|UniProtKB:P16152};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.10 mM for menadione {ECO:0000269|PubMed:7705364};
CC KM=0.24 mM for prostaglandin E2 {ECO:0000269|PubMed:7705364};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q28960}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q28960}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; X84349; CAA59088.1; -; mRNA.
DR EMBL; X95986; CAA65230.1; -; Genomic_DNA.
DR EMBL; D89069; BAA19007.1; -; mRNA.
DR EMBL; BC105893; AAI05894.1; -; mRNA.
DR PIR; S68982; JC5284.
DR RefSeq; NP_062043.1; NM_019170.2.
DR AlphaFoldDB; P47727; -.
DR SMR; P47727; -.
DR BioGRID; 247902; 1.
DR IntAct; P47727; 1.
DR MINT; P47727; -.
DR STRING; 10116.ENSRNOP00000064050; -.
DR iPTMnet; P47727; -.
DR PhosphoSitePlus; P47727; -.
DR jPOST; P47727; -.
DR PaxDb; P47727; -.
DR PRIDE; P47727; -.
DR GeneID; 29224; -.
DR KEGG; rno:29224; -.
DR UCSC; RGD:2286; rat.
DR CTD; 873; -.
DR RGD; 2286; Cbr1.
DR eggNOG; KOG1208; Eukaryota.
DR InParanoid; P47727; -.
DR OrthoDB; 1259665at2759; -.
DR PhylomeDB; P47727; -.
DR TreeFam; TF329359; -.
DR Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR PRO; PR:P47727; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005902; C:microvillus; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0035003; C:subapical complex; ISO:RGD.
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:RGD.
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; ISO:RGD.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; ISO:RGD.
DR GO; GO:0050221; F:prostaglandin-E2 9-reductase activity; ISS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0008211; P:glucocorticoid metabolic process; ISO:RGD.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IEP:RGD.
DR GO; GO:0042376; P:phylloquinone catabolic process; IDA:RGD.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:1905344; P:prostaglandin catabolic process; IDA:RGD.
DR GO; GO:0032355; P:response to estradiol; IDA:RGD.
DR GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0032570; P:response to progesterone; IDA:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0006706; P:steroid catabolic process; IDA:RGD.
DR GO; GO:0042373; P:vitamin K metabolic process; ISS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS: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 Acetylation; Cytoplasm; Direct protein sequencing; Lipid metabolism; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT CHAIN 2..277
FT /note="Carbonyl reductase [NADPH] 1"
FT /id="PRO_0000054607"
FT REGION 258..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 10..34
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 63..64
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 95..97
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 106
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 140
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 193..194
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 194..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT BINDING 231..233
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 239
FT /note="N6-1-carboxyethyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT CONFLICT 22
FT /note="V -> T (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="V -> D (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="V -> H (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 141..144
FT /note="SVSL -> GMSR (in Ref. 2; BAA19007)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="I -> V (in Ref. 3; AAI05894)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="N -> T (in Ref. 3; AAI05894)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="A -> T (in Ref. 2; BAA19007)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="K -> E (in Ref. 2; BAA19007)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 277 AA; 30578 MW; B0F4738C40011B5B CRC64;
MSSDRPVALV TGANKGIGFA IVRDLCRKFL GDVVLTARDE SRGHEAVKQL QTEGLSPRFH
QLDIDNPQSI RALRDFLLQE YGGLNVLVNN AGIAFKVVDP TPFHIQAEVT MKTNFFGTQD
VCKELLPIIK PQGRVVNVSS SVSLRALKSC SPELQQKFRS ETITEEELVG LMNKFIEDAK
KGVHAKEGWP NSAYGVTKIG VTVLSRIYAR KLNEERREDK ILLNACCPGW VRTDMAGPKA
TKSPEEGAET PVYLALLPPG AEGPHGQFVQ DKKVEPW
