PGDH_RAT
ID PGDH_RAT Reviewed; 266 AA.
AC O08699; Q6P687;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=15-hydroxyprostaglandin dehydrogenase [NAD(+)];
DE Short=15-PGDH;
DE EC=1.1.1.141 {ECO:0000305|PubMed:9099857};
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Intestine;
RX PubMed=9099857; DOI=10.1016/s0378-1119(96)00774-3;
RA Zhang H., Matsuo M., Zhou H., Ensor C.M., Tai H.-H.;
RT "Cloning and expression of the cDNA for rat NAD+-dependent 15-
RT hydroxyprostaglandin dehydrogenase.";
RL Gene 188:41-44(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 (PubMed:9099857) (By similarity). Decreases the levels of the pro-
CC proliferative prostaglandins such as prostaglandin E2 (whose activity
CC is increased in cancer because of an increase in the expression of
CC cyclooxygenase 2) and generates oxo-fatty acid products that can
CC profoundly influence cell function by abrogating pro-inflammatory
CC cytokine expression. Converts resolvins E1, D1 and D2 to their oxo
CC products, which represents a mode of resolvin inactivation. Resolvin E1
CC plays important roles during the resolution phase of acute
CC inflammation, while resolvins D1 and D2 have a unique role in obesity-
CC induced adipose inflammation (By similarity).
CC {ECO:0000250|UniProtKB:P15428, ECO:0000269|PubMed:9099857}.
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:0000305|PubMed:9099857};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11877;
CC Evidence={ECO:0000305|PubMed:9099857};
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; U44750; AAB53027.1; -; mRNA.
DR EMBL; BC062399; AAH62399.1; -; mRNA.
DR RefSeq; NP_077366.2; NM_024390.2.
DR AlphaFoldDB; O08699; -.
DR SMR; O08699; -.
DR STRING; 10116.ENSRNOP00000014229; -.
DR BindingDB; O08699; -.
DR iPTMnet; O08699; -.
DR PhosphoSitePlus; O08699; -.
DR PaxDb; O08699; -.
DR Ensembl; ENSRNOT00000014229; ENSRNOP00000014229; ENSRNOG00000010610.
DR GeneID; 79242; -.
DR KEGG; rno:79242; -.
DR UCSC; RGD:620087; rat.
DR CTD; 3248; -.
DR RGD; 620087; Hpgd.
DR eggNOG; KOG4169; Eukaryota.
DR GeneTree; ENSGT00940000154593; -.
DR HOGENOM; CLU_010194_2_16_1; -.
DR InParanoid; O08699; -.
DR OMA; QGIHFQN; -.
DR OrthoDB; 1053465at2759; -.
DR PhylomeDB; O08699; -.
DR TreeFam; TF324093; -.
DR BRENDA; 1.1.1.141; 5301.
DR Reactome; R-RNO-2142700; Synthesis of Lipoxins (LX).
DR Reactome; R-RNO-9018676; Biosynthesis of D-series resolvins.
DR Reactome; R-RNO-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR PRO; PR:O08699; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000010610; Expressed in duodenum and 19 other tissues.
DR Genevisible; O08699; RN.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0016404; F:15-hydroxyprostaglandin dehydrogenase (NAD+) activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
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; ISO:RGD.
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; IEP:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
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:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0006693; P:prostaglandin metabolic process; IDA:RGD.
DR GO; GO:1905828; P:regulation of prostaglandin catabolic process; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IDA:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0070493; P:thrombin-activated receptor signaling pathway; IEP: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 1: Evidence at protein level;
KW Cytoplasm; Fatty acid metabolism; Lipid metabolism; NAD; Oxidoreductase;
KW Prostaglandin metabolism; Reference proteome; Tumor suppressor.
FT CHAIN 1..266
FT /note="15-hydroxyprostaglandin dehydrogenase [NAD(+)]"
FT /id="PRO_0000253627"
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"
FT CONFLICT 146
FT /note="A -> T (in Ref. 1; AAB53027)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 266 AA; 28939 MW; AF9CCD6185ABD6C0 CRC64;
MHVNGKVALV TGAAQGIGKA FTEALLLHGA KVALVDWNLE TGVKCKAALD EQFEPQKTLF
IQCDVADQKQ LRDTFRKVVD HFGRLDILVN NAGVNNEKNW EQTLQINLVS VISGTYLGLD
YMSKQNGGEG GIIINISSIA GLMPVAQQPV YCASKHGIIG FTRSAAMAAN LMKSGVRLNV
ICPGFVKTPI LESIEKEENM GQYIEYTDQI KAMMKFYGIL DPSAIANGLI NLIEDDALNG
AIMKITASKG IHFQDYDLFP SFSKAP
