CBR1_MOUSE
ID CBR1_MOUSE Reviewed; 277 AA.
AC P48758; Q91X28;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 3.
DT 03-AUG-2022, entry version 163.
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|MGI:MGI:88284};
GN Synonyms=Cbr {ECO:0000312|MGI:MGI:88284};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CBA/CJ; TISSUE=Cerebellum;
RX PubMed=8661038; DOI=10.1006/geno.1996.0255;
RA Wei J., Dlouhy S.R., Hara A., Ghetti B., Hodes M.E.;
RT "Cloning a cDNA for carbonyl reductase (Cbr) from mouse cerebellum: murine
RT genes that express cbr map to chromosomes 16 and 11.";
RL Genomics 34:147-148(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 [3]
RP PROTEIN SEQUENCE OF 59-71; 80-96 AND 221-232, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Klug S., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-30, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=33785425; DOI=10.1016/j.molmet.2021.101225;
RA Bell R.M.B., Villalobos E., Nixon M., Miguelez-Crespo A., Murphy L.,
RA Fawkes A., Coutts A., Sharp M.G.F., Koerner M.V., Allan E., Meijer O.C.,
RA Houtman R., Odermatt A., Beck K.R., Denham S.G., Lee P., Homer N.Z.M.,
RA Walker B.R., Morgan R.A.;
RT "Carbonyl reductase 1 amplifies glucocorticoid action in adipose tissue and
RT impairs glucose tolerance in lean mice.";
RL Mol. Metab. 48:101225-101225(2021).
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 (By similarity). Can convert prostaglandin E to
CC prostaglandin F2-alpha (By similarity). Can bind glutathione, which
CC explains its higher affinity for glutathione-conjugated substrates.
CC Catalyzes the reduction of S-nitrosoglutathione. In addition,
CC participates in the glucocorticoid metabolism by catalyzing the NADPH-
CC dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF)
CC or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1
CC and NR3C2 in adipose tissue (PubMed:28878267, PubMed:33785425).
CC {ECO:0000250|UniProtKB:P16152, ECO:0000250|UniProtKB:Q28960,
CC ECO:0000269|PubMed:28878267, ECO:0000269|PubMed:33785425}.
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:P16152};
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:33785425};
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=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:0000269|PubMed:33785425};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70220;
CC Evidence={ECO:0000269|PubMed:33785425};
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 -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q28960}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q28960}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal. {ECO:0000269|PubMed:33785425}.
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; U31966; AAB19006.1; -; mRNA.
DR EMBL; BC012714; AAH12714.1; -; mRNA.
DR CCDS; CCDS28341.1; -.
DR RefSeq; NP_031646.2; NM_007620.2.
DR AlphaFoldDB; P48758; -.
DR SMR; P48758; -.
DR BioGRID; 198531; 8.
DR STRING; 10090.ENSMUSP00000049394; -.
DR iPTMnet; P48758; -.
DR PhosphoSitePlus; P48758; -.
DR SwissPalm; P48758; -.
DR REPRODUCTION-2DPAGE; P48758; -.
DR CPTAC; non-CPTAC-3416; -.
DR CPTAC; non-CPTAC-3775; -.
DR EPD; P48758; -.
DR jPOST; P48758; -.
DR MaxQB; P48758; -.
DR PaxDb; P48758; -.
DR PRIDE; P48758; -.
DR ProteomicsDB; 265567; -.
DR DNASU; 12408; -.
DR Ensembl; ENSMUST00000039659; ENSMUSP00000049394; ENSMUSG00000051483.
DR GeneID; 12408; -.
DR KEGG; mmu:12408; -.
DR UCSC; uc007zzr.1; mouse.
DR CTD; 873; -.
DR MGI; MGI:88284; Cbr1.
DR VEuPathDB; HostDB:ENSMUSG00000051483; -.
DR eggNOG; KOG1208; Eukaryota.
DR GeneTree; ENSGT00510000046499; -.
DR HOGENOM; CLU_010194_9_0_1; -.
DR InParanoid; P48758; -.
DR OMA; LALQYPK; -.
DR OrthoDB; 1259665at2759; -.
DR PhylomeDB; P48758; -.
DR TreeFam; TF329359; -.
DR BRENDA; 1.1.1.184; 3474.
DR Reactome; R-MMU-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR SABIO-RK; P48758; -.
DR BioGRID-ORCS; 12408; 3 hits in 79 CRISPR screens.
DR ChiTaRS; Cbr1; mouse.
DR PRO; PR:P48758; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; P48758; protein.
DR Bgee; ENSMUSG00000051483; Expressed in epithelium of stomach and 274 other tissues.
DR ExpressionAtlas; P48758; baseline and differential.
DR Genevisible; P48758; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0035003; C:subapical complex; IDA:MGI.
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; ISS: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; ISO:MGI.
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:0008211; P:glucocorticoid metabolic process; IDA:UniProtKB.
DR GO; GO:0042376; P:phylloquinone catabolic process; ISO:MGI.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:1905344; P:prostaglandin catabolic process; ISO:MGI.
DR GO; GO:0032355; P:response to estradiol; ISO:MGI.
DR GO; GO:0032570; P:response to progesterone; ISO:MGI.
DR GO; GO:0006706; P:steroid catabolic process; ISO:MGI.
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_0000054603"
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:0000250|UniProtKB:P47727"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 239
FT /note="N6-1-carboxyethyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT CONFLICT 90
FT /note="N -> K (in Ref. 1; AAB19006)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="K -> E (in Ref. 1; AAB19006)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="G -> E (in Ref. 1; AAB19006)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 277 AA; 30641 MW; 6053423B6D5F82B7 CRC64;
MSSSRPVALV TGANKGIGFA ITRDLCRKFS GDVVLAARDE ERGQTAVQKL QAEGLSPRFH
QLDIDNPQSI RALRDFLLKE YGGLDVLVNN AGIAFKVNDD TPFHIQAEVT MKTNFFGTRD
VCKELLPLIK PQGRVVNVSS MVSLRALKNC RLELQQKFRS ETITEEELVG LMNKFVEDTK
KGVHAEEGWP NSAYGVTKIG VTVLSRILAR KLNEQRRGDK ILLNACCPGW VRTDMAGPKA
TKSPEEGAET PVYLALLPPD AEGPHGQFVQ DKKVEPW
