CBR1_PONAB
ID CBR1_PONAB Reviewed; 277 AA.
AC Q5RCU5;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 89.
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:0000250|UniProtKB:P16152};
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC {ECO:0000250|UniProtKB:P16152, ECO:0000250|UniProtKB:Q28960}.
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:0000250|UniProtKB:P16152};
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 -!- 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; CR858173; CAH90412.1; -; mRNA.
DR RefSeq; NP_001125206.1; NM_001131734.1.
DR AlphaFoldDB; Q5RCU5; -.
DR SMR; Q5RCU5; -.
DR STRING; 9601.ENSPPYP00000012724; -.
DR GeneID; 100172097; -.
DR KEGG; pon:100172097; -.
DR CTD; 873; -.
DR eggNOG; KOG1208; Eukaryota.
DR InParanoid; Q5RCU5; -.
DR OrthoDB; 1259665at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0050221; F:prostaglandin-E2 9-reductase activity; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Lipid metabolism; NADP; Oxidoreductase;
KW 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_0000054605"
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:0000250|UniProtKB:P48758"
FT MOD_RES 239
FT /note="N6-1-carboxyethyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P16152"
SQ SEQUENCE 277 AA; 30391 MW; 457D1755F56ADBD2 CRC64;
MSSGMHVALV TGGNKGIGLA IVRDLCRLFS GDVVLTARDV ARGQAAVQQL QAEGLSPRFH
QLDIDDLQSI RALRDFLRKE YGGLDVLVNN AGIAFKVADP TPFHIQAEVT MKTNFFGTRD
VCTELLPLIK PQGRVVNVSS IMSVRALKSC SPELQQKFRS ETITEEELVG LMNKFVEDTK
KGVHQKEGWP SSAYGVTKIG VTVLSRIHAR KLSEQRKGDR ILLNACCPGW VRTDMAGPKA
TKSPEEGAET PVYLALLPPD AEGPHGQFVS EKRVEQW
