CBR1_PIG
ID CBR1_PIG Reviewed; 289 AA.
AC Q28960;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Carbonyl reductase [NADPH] 1 {ECO:0000305};
DE EC=1.1.1.184 {ECO:0000269|PubMed:1597188};
DE AltName: Full=15-hydroxyprostaglandin dehydrogenase [NADP(+)] {ECO:0000303|PubMed:1597188};
DE EC=1.1.1.196 {ECO:0000269|PubMed:1597188};
DE EC=1.1.1.197 {ECO:0000250|UniProtKB:P16152};
DE AltName: Full=20-beta-hydroxysteroid dehydrogenase {ECO:0000303|PubMed:1377683};
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:0000303|PubMed:1597188};
DE Short=PG-9-KR {ECO:0000303|PubMed:1597188};
DE AltName: Full=Prostaglandin-E(2) 9-reductase {ECO:0000303|PubMed:1597188};
DE EC=1.1.1.189 {ECO:0000269|PubMed:1597188};
GN Name=CBR1 {ECO:0000250|UniProtKB:P16152}; Synonyms=CBR, CRN;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 80-111; 113-127; 131-152;
RP 160-174; 187-211; 221-239 AND 243-272, FUNCTION, CATALYTIC ACTIVITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=1377683; DOI=10.1016/s0021-9258(18)42232-6;
RA Tanaka M., Ohno S., Nakajin S., Shinoda M., Nagahama Y.;
RT "Pig testicular 20-beta-hydroxysteroid dehydrogenase exhibits carbonyl
RT reductase-like structure and activity: cDNA cloning of pig testicular 2-
RT beta-hydroxysteroid dehydrogenase.";
RL J. Biol. Chem. 267:13451-13455(1992).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
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 [3]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH NADP, AND SUBUNIT
RP STRUCTURE.
RX PubMed=11279087; DOI=10.1074/jbc.m100538200;
RA Ghosh D., Sawicki M., Pletnev V., Erman M., Ohno S., Nakajin S., Duax W.L.;
RT "Porcine carbonyl reductase. Structural basis for a functional monomer in
RT short chain dehydrogenases/reductases.";
RL J. Biol. Chem. 276:18457-18463(2001).
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. Can convert prostaglandin E2 to prostaglandin F2-
CC alpha (PubMed:1377683, PubMed:1597188). 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:0000269|PubMed:1377683,
CC ECO:0000269|PubMed:1597188}.
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:1597188};
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=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:1597188};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:24510;
CC Evidence={ECO:0000305|PubMed:1597188};
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:0000269|PubMed:1597188};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20745;
CC Evidence={ECO:0000305|PubMed:1597188};
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:0000269|PubMed:1597188};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63477;
CC Evidence={ECO:0000305|PubMed:1597188};
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:0000269|PubMed:1597188};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63481;
CC Evidence={ECO:0000305|PubMed:1597188};
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:1377683, ECO:0000269|PubMed:1597188};
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:1597188};
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:0000269|PubMed:1597188};
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=160 uM for prostaglandin E2 {ECO:0000269|PubMed:1597188};
CC KM=310 uM for menadione {ECO:0000269|PubMed:1597188};
CC KM=2.3 uM for 9,1 O-phenanthrene-quinone
CC {ECO:0000269|PubMed:1597188};
CC KM=450 uM for 4-nitrobenzaldehyde {ECO:0000269|PubMed:1597188};
CC KM=5.2 uM for NADPH {ECO:0000269|PubMed:1597188};
CC Vmax=0.059 umol/min/mg enzyme towards prostaglandin E2
CC {ECO:0000269|PubMed:1597188};
CC Vmax=9.4 umol/min/mg enzyme towards menadione
CC {ECO:0000269|PubMed:1597188};
CC Vmax=15.2 umol/min/mg enzyme towards 9,1 O-phenanthrene-quinone
CC {ECO:0000269|PubMed:1597188};
CC Vmax=1.9 umol/min/mg enzyme towards 4-nitrobenzaldehyde
CC {ECO:0000269|PubMed:1597188};
CC Note=kcats are 2 min(-1), 285 min(-1), 460 min(-1), 58 min(-1) for
CC prostaglandin E2, menadione, 9,1 O-phenanthrene-quinone and 4-
CC nitrobenzaldehyde as substrates, respectively.
CC {ECO:0000269|PubMed:1597188};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11279087}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney (at protein level).
CC {ECO:0000269|PubMed:1597188}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in testis from newborns. After 30
CC days the levels are markedly decreased. {ECO:0000269|PubMed:1377683}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; M80709; AAA30980.1; -; mRNA.
DR PIR; A42912; A42912.
DR RefSeq; NP_999238.1; NM_214073.1.
DR PDB; 1N5D; X-ray; 2.30 A; A=2-289.
DR PDBsum; 1N5D; -.
DR AlphaFoldDB; Q28960; -.
DR SMR; Q28960; -.
DR SwissLipids; SLP:000001473; -.
DR PeptideAtlas; Q28960; -.
DR PRIDE; Q28960; -.
DR Ensembl; ENSSSCT00000062193; ENSSSCP00000052333; ENSSSCG00000031111.
DR Ensembl; ENSSSCT00045036349; ENSSSCP00045025284; ENSSSCG00045021225.
DR Ensembl; ENSSSCT00065082755; ENSSSCP00065036060; ENSSSCG00065060377.
DR Ensembl; ENSSSCT00070022530; ENSSSCP00070018650; ENSSSCG00070011561.
DR GeneID; 397143; -.
DR KEGG; ssc:397143; -.
DR CTD; 873; -.
DR GeneTree; ENSGT00510000046499; -.
DR InParanoid; Q28960; -.
DR OMA; YRYSASD; -.
DR OrthoDB; 1259665at2759; -.
DR BRENDA; 1.1.1.184; 6170.
DR BRENDA; 1.1.1.189; 6170.
DR EvolutionaryTrace; Q28960; -.
DR Proteomes; UP000008227; Chromosome 13.
DR Proteomes; UP000314985; Chromosome 13.
DR Bgee; ENSSSCG00000031111; Expressed in lymph node and 14 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0047021; F:15-hydroxyprostaglandin dehydrogenase (NADP+) activity; IDA: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:0050221; F:prostaglandin-E2 9-reductase activity; IDA: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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT CHAIN 2..289
FT /note="Carbonyl reductase [NADPH] 1"
FT /id="PRO_0000054604"
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:0000269|PubMed:11279087"
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 239
FT /note="N6-1-carboxyethyl lysine"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT STRAND 7..12
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 16..28
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 30..39
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 40..51
FT /evidence="ECO:0007829|PDB:1N5D"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 67..81
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 103..114
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 116..125
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 129..138
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 152..159
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 165..180
FT /evidence="ECO:0007829|PDB:1N5D"
FT TURN 184..188
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 193..215
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:1N5D"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:1N5D"
FT HELIX 249..255
FT /evidence="ECO:0007829|PDB:1N5D"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:1N5D"
SQ SEQUENCE 289 AA; 31693 MW; 47A587FFE3F682C2 CRC64;
MSSNTRVALV TGANKGIGFA IVRDLCRQFA GDVVLTARDV ARGQAAVKQL QAEGLSPRFH
QLDIIDLQSI RALCDFLRKE YGGLDVLVNN AAIAFQLDNP TPFHIQAELT MKTNFMGTRN
VCTELLPLIK PQGRVVNVSS TEGVRALNEC SPELQQKFKS ETITEEELVG LMNKFVEDTK
NGVHRKEGWS DSTYGVTKIG VSVLSRIYAR KLREQRAGDK ILLNACCPGW VRTDMGGPKA
PKSPEVGAET PVYLALLPSD AEGPHGQFVT DKKVVEWGVP PESYPWVNA
