PGDH_CAVPO
ID PGDH_CAVPO Reviewed; 265 AA.
AC P70684;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=15-hydroxyprostaglandin dehydrogenase [NAD(+)];
DE Short=15-PGDH;
DE EC=1.1.1.141 {ECO:0000250|UniProtKB:P15428};
DE AltName: Full=Eicosanoid/docosanoid dehydrogenase [NAD(+)];
DE EC=1.1.1.- {ECO:0000250|UniProtKB:P15428};
DE EC=1.1.1.232 {ECO:0000250|UniProtKB:P15428};
DE AltName: Full=Prostaglandin dehydrogenase 1;
GN Name=HPGD; Synonyms=PGDH1;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Dunkin-Hartley; TISSUE=Uterus;
RX PubMed=8977409; DOI=10.1210/endo.138.1.4889;
RA Bracken K.E., Elger W., Jantke I., Nanninga A., Gellersen B.;
RT "Cloning of guinea pig cyclooxygenase-2 and 15-hydroxyprostaglandin
RT dehydrogenase complementary deoxyribonucleic acids: steroid-modulated gene
RT expression correlates to prostaglandin F2 alpha secretion in cultured
RT endometrial cells.";
RL Endocrinology 138:237-247(1997).
CC -!- FUNCTION: Catalyzes the NAD-dependent dehydrogenation (oxidation) of a
CC broad array of hydroxylated polyunsaturated fatty acids (mainly
CC eicosanoids and docosanoids, including prostaglandins, lipoxins and
CC resolvins), yielding their corresponding keto (oxo) metabolites.
CC Decreases the levels of the pro-proliferative prostaglandins such as
CC prostaglandin E2 (whose activity is increased in cancer because of an
CC increase in the expression of cyclooxygenase 2) and generates oxo-fatty
CC acid products that can profoundly influence cell function by abrogating
CC pro-inflammatory cytokine expression. Converts resolvins E1, D1 and D2
CC to their oxo products, which represents a mode of resolvin
CC inactivation. Resolvin E1 plays important roles during the resolution
CC phase of acute inflammation, while resolvins D1 and D2 have a unique
CC role in obesity-induced adipose inflammation.
CC {ECO:0000250|UniProtKB:P15428}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + prostaglandin E2 = 15-oxoprostaglandin E2 + H(+) +
CC NADH; Xref=Rhea:RHEA:11876, ChEBI:CHEBI:15378, ChEBI:CHEBI:57400,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:606564;
CC EC=1.1.1.141; Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11877;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + NAD(+) = 15-
CC oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H(+) + NADH;
CC Xref=Rhea:RHEA:23260, ChEBI:CHEBI:15378, ChEBI:CHEBI:57409,
CC ChEBI:CHEBI:57410, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.232; Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23261;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate + NAD(+) = 11-
CC oxo-(5Z,8Z,12E,14Z)-eicosatetraenoate + H(+) + NADH;
CC Xref=Rhea:RHEA:48640, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78836, ChEBI:CHEBI:90697;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48641;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lipoxin A4 + NAD(+) = 15-oxo-(5S,6R)-dihydroxy-
CC (7E,9E,11Z,13E)-eicosatetraenoate + H(+) + NADH;
CC Xref=Rhea:RHEA:41572, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:67026, ChEBI:CHEBI:78311;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41573;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z)-eicosatrienoate + H(+) +
CC NADH = (5S,6R,15S)-trihydroxy-(7E,9E,11Z)-eicosatrienoate + NAD(+);
CC Xref=Rhea:RHEA:41596, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:78325, ChEBI:CHEBI:78329;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41597;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + prostaglandin A1 = 15-oxo-prostaglandin A1 + H(+) +
CC NADH; Xref=Rhea:RHEA:41263, ChEBI:CHEBI:15378, ChEBI:CHEBI:57398,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:85072;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41264;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + prostaglandin E1 = 15-oxoprostaglandin E1 + H(+) +
CC NADH; Xref=Rhea:RHEA:16477, ChEBI:CHEBI:15378, ChEBI:CHEBI:57397,
CC ChEBI:CHEBI:57401, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16478;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=14-hydroxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + NAD(+) =
CC 14-oxo-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate + H(+) + NADH;
CC Xref=Rhea:RHEA:48952, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:90866, ChEBI:CHEBI:90867;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48953;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + resolvin E1 = 18-oxo-resolvin E1 + H(+) + NADH;
CC Xref=Rhea:RHEA:49244, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:91000, ChEBI:CHEBI:91001;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49245;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + resolvin D1 = 8-oxoresolvin D1 + H(+) + NADH;
CC Xref=Rhea:RHEA:50124, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:132079, ChEBI:CHEBI:132080;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50125;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + resolvin D1 = 17-oxoresolvin D1 + H(+) + NADH;
CC Xref=Rhea:RHEA:50128, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:132079, ChEBI:CHEBI:132081;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50129;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + resolvin D2 = 7-oxoresolvin D2 + H(+) + NADH;
CC Xref=Rhea:RHEA:53584, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:133367, ChEBI:CHEBI:137497;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53585;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NAD(+) + resolvin D2 = 16-oxoresolvin D2 + H(+) + NADH;
CC Xref=Rhea:RHEA:53588, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:133367, ChEBI:CHEBI:137498;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53589;
CC Evidence={ECO:0000250|UniProtKB:P15428};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; Y07953; CAA69251.1; -; mRNA.
DR RefSeq; NP_001166432.1; NM_001172961.1.
DR AlphaFoldDB; P70684; -.
DR SMR; P70684; -.
DR STRING; 10141.ENSCPOP00000001789; -.
DR GeneID; 100135538; -.
DR KEGG; cpoc:100135538; -.
DR CTD; 3248; -.
DR eggNOG; KOG4169; Eukaryota.
DR InParanoid; P70684; -.
DR OrthoDB; 1053465at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016404; F:15-hydroxyprostaglandin dehydrogenase (NAD+) activity; ISS:UniProtKB.
DR GO; GO:0051287; F:NAD binding; ISS:UniProtKB.
DR GO; GO:0070403; F:NAD+ binding; ISS:UniProtKB.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; ISS:UniProtKB.
DR GO; GO:0004957; F:prostaglandin E receptor activity; ISS:UniProtKB.
DR GO; GO:0097070; P:ductus arteriosus closure; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0030728; P:ovulation; ISS:UniProtKB.
DR GO; GO:0007567; P:parturition; ISS:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISS:UniProtKB.
DR GO; GO:1905828; P:regulation of prostaglandin catabolic process; ISS:UniProtKB.
DR GO; GO:0070493; P:thrombin-activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
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 Cytoplasm; Fatty acid metabolism; Lipid metabolism; NAD; Oxidoreductase;
KW Prostaglandin metabolism; Reference proteome; Tumor suppressor.
FT CHAIN 1..265
FT /note="15-hydroxyprostaglandin dehydrogenase [NAD(+)]"
FT /id="PRO_0000253625"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 12..20
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 36..37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 63..65
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 151..155
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 186..188
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 265 AA; 28886 MW; 842D1B8D1C951A20 CRC64;
MHVNGKVALV TGAAQGIGRA FAEGLLHKGA KVALVDWNLE AGVKCKAALD EEFEPQKTLF
IQCDVADQEQ LRDTFTKVVD YFGRLDILVN NAGVNNEKNW EKTLQINLVS VISGTYLGLD
YMSKQHGGEG GVIINMSSLA GLMPVAQQPV YCASKHGIIG FTRSAAMARK LMNSGVRMNA
ICPGFVNTSI LQSIEKEENM GPYIEYTGHI KDMMKCYGIL DPEMIANGLI TLIEDDDLNG
AIMKITTSNG IHFQDYDTAP SYAKD
