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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
 
 
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