PE2R_RABIT
ID PE2R_RABIT Reviewed; 323 AA.
AC P80508;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Prostaglandin-E(2) 9-reductase;
DE EC=1.1.1.189;
DE AltName: Full=20-alpha-hydroxysteroid dehydrogenase;
DE Short=20-alpha-HSD;
DE EC=1.1.1.149;
GN Name=AKR1C5;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Ovary;
RX PubMed=8446108; DOI=10.1210/mend.7.1.8446108;
RA Lacy W.R., Washenick K.J., Cook R.G., Dunbar B.S.;
RT "Molecular cloning and expression of an abundant rabbit ovarian protein
RT with 20 alpha-hydroxysteroid dehydrogenase activity.";
RL Mol. Endocrinol. 7:58-66(1993).
RN [2]
RP ERRATUM OF PUBMED:8446108.
RX PubMed=8247025; DOI=10.1210/mend.7.9.8247025;
RA Lacy W.R., Dunbar B.S.;
RL Mol. Endocrinol. 7:1239-1239(1993).
RN [3]
RP PROTEIN SEQUENCE OF 134-170 AND 279-314.
RC TISSUE=Corpus luteum;
RX PubMed=8529651; DOI=10.1111/j.1432-1033.1995.264_c.x;
RA Wintergalen N., Thole H.H., Galla H.-J., Schlegel W.;
RT "Prostaglandin-E2 9-reductase from corpus luteum of pseudopregnant rabbit
RT is a member of the aldo-keto reductase superfamily featuring 20 alpha-
RT hydroxysteroid dehydrogenase activity.";
RL Eur. J. Biochem. 234:264-270(1995).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.32 ANGSTROMS) IN COMPLEX WITH NADPH; NADP AND
RP TESTOSTERONE, AND MUTAGENESIS OF PHE-54 AND VAL-306.
RX PubMed=15123423; DOI=10.1016/j.jmb.2004.03.035;
RA Couture J.-F., Legrand P., Cantin L., Labrie F., Luu-The V., Breton R.;
RT "Loop relaxation, a mechanism that explains the reduced specificity of
RT rabbit 20alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto
RT reductase superfamily.";
RL J. Mol. Biol. 339:89-102(2004).
CC -!- FUNCTION: Can convert prostaglandin E2 to prostaglandin F2-alpha.
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;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NADP(+) = 17alpha-
CC hydroxyprogesterone + H(+) + NADPH; Xref=Rhea:RHEA:15857,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16418, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.149;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(17R,20S)-17,20-dihydroxypregn-4-en-3-one + NAD(+) = 17alpha-
CC hydroxyprogesterone + H(+) + NADH; Xref=Rhea:RHEA:15853,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16418, ChEBI:CHEBI:17252,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.149;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; L17006; AAA31155.1; -; mRNA.
DR PIR; A45366; A45366.
DR RefSeq; NP_001075719.1; NM_001082250.1.
DR PDB; 1Q13; X-ray; 2.08 A; A/B=1-323.
DR PDB; 1Q5M; X-ray; 1.32 A; A/B=2-323.
DR PDBsum; 1Q13; -.
DR PDBsum; 1Q5M; -.
DR AlphaFoldDB; P80508; -.
DR SMR; P80508; -.
DR STRING; 9986.ENSOCUP00000017578; -.
DR GeneID; 100009071; -.
DR KEGG; ocu:100009071; -.
DR CTD; 100009071; -.
DR eggNOG; KOG1577; Eukaryota.
DR HOGENOM; CLU_023205_0_0_1; -.
DR InParanoid; P80508; -.
DR OMA; RMNFPAR; -.
DR OrthoDB; 1016440at2759; -.
DR TreeFam; TF106492; -.
DR EvolutionaryTrace; P80508; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0047006; F:17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050221; F:prostaglandin-E2 9-reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd19108; AKR_AKR1C1-35; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044482; AKR1C.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; NADP; Oxidoreductase; Prostaglandin biosynthesis;
KW Prostaglandin metabolism; Reference proteome.
FT CHAIN 1..323
FT /note="Prostaglandin-E(2) 9-reductase"
FT /id="PRO_0000124651"
FT ACT_SITE 55
FT /note="Proton donor"
FT BINDING 23..24
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15123423"
FT BINDING 24
FT /ligand="substrate"
FT BINDING 50
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15123423"
FT BINDING 117
FT /ligand="substrate"
FT BINDING 166..167
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15123423"
FT BINDING 190
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15123423"
FT BINDING 216..221
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15123423"
FT BINDING 270..280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15123423"
FT SITE 54
FT /note="Required for substrate specificity"
FT SITE 84
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT MUTAGEN 54
FT /note="F->L: 49% reduction in 20alpha-HSD activity; little
FT effect on 3-alpha-HSD."
FT /evidence="ECO:0000269|PubMed:15123423"
FT MUTAGEN 54
FT /note="F->V: 73% reduction in 20alpha-HSD activity; little
FT effect on 3-alpha-HSD."
FT /evidence="ECO:0000269|PubMed:15123423"
FT MUTAGEN 306
FT /note="V->F: Greatly reduced 3alpha-HSD activity toward
FT DHT; little effect on 20alpha-HSD activity."
FT /evidence="ECO:0000269|PubMed:15123423"
FT HELIX 3..5
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 7..9
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 15..22
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 31..44
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 92..106
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:1Q13"
FT HELIX 144..156
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 159..167
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 200..208
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:1Q5M"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 252..261
FT /evidence="ECO:0007829|PDB:1Q5M"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 274..281
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:1Q5M"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:1Q5M"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:1Q5M"
SQ SEQUENCE 323 AA; 36670 MW; 110ADD9FF56061B7 CRC64;
MDPKFQRVAL SDGHFIPVLG FGTYAPEEVP KSKAMEATKI AIDAGFRHID SAYFYKNEKE
VGLAIRSKIA DGTVKREDIF YTSKLWCTFH RPELVRPSLE DSLKNLQLDY VDLYIIHFPT
ALKPGVEIIP TDEHGKAIFD TVDICATWEA MEKCKDAGLA KSIGVSNFNR RQLEMILNKP
GLKYKPVCNQ VECHPYLNQG KLLEFCKSKG IVLVAYSALG SHREPEWVDQ SAPVLLEDPL
IGALAKKHQQ TPALIALRYQ LQRGIVVLAK SFTEKRIKEN IQVFEFQLPS EDMKVIDSLN
RNFRYVTADF AIGHPNYPFS DEY
