PTGR1_RAT
ID PTGR1_RAT Reviewed; 329 AA.
AC P97584; Q5EBD3;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Prostaglandin reductase 1;
DE Short=PRG-1 {ECO:0000250|UniProtKB:Q14914};
DE AltName: Full=15-oxoprostaglandin 13-reductase {ECO:0000303|PubMed:11524419};
DE EC=1.3.1.48 {ECO:0000250|UniProtKB:Q14914};
DE AltName: Full=Dithiolethione-inducible gene 1 protein {ECO:0000303|PubMed:8968041};
DE Short=D3T-inducible gene 1 protein {ECO:0000303|PubMed:8968041};
DE Short=DIG-1 {ECO:0000303|PubMed:8968041};
DE AltName: Full=Leukotriene B4 12-hydroxydehydrogenase {ECO:0000303|PubMed:11524419};
DE AltName: Full=NAD(P)H-dependent alkenal/one oxidoreductase;
DE EC=1.3.1.74 {ECO:0000269|PubMed:11524419};
GN Name=Ptgr1; Synonyms=Dig1, Ltb4dh;
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], AND INDUCTION BY DITHIOLETHIONE.
RC STRAIN=Fischer 344;
RX PubMed=8968041; DOI=10.1093/carcin/17.11.2297;
RA Primiano T., Gastel J.A., Kensler T.W., Sutter T.R.;
RT "Isolation of cDNAs representing dithiolethione-responsive genes.";
RL Carcinogenesis 17:2297-2303(1996).
RN [2]
RP SEQUENCE REVISION.
RA Kensler T.W.;
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11524419; DOI=10.1074/jbc.m105487200;
RA Dick R.A., Kwak M.K., Sutter T.R., Kensler T.W.;
RT "Antioxidative function and substrate specificity of NAD(P)H-dependent
RT alkenal/one oxidoreductase. A new role for leukotriene B4 12-
RT hydroxydehydrogenase/15-oxoprostaglandin 13-reductase.";
RL J. Biol. Chem. 276:40803-40810(2001).
CC -!- FUNCTION: NAD(P)H-dependent oxidoreductase involved in metabolic
CC inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins
CC (PG), leukotrienes (LT) and lipoxins (LX) (By similarity). Catalyzes
CC with high efficiency the reduction of the 13,14 double bond of 15-
CC oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-
CC oxo-PGF2-alpha (PubMed:11524419) (By similarity). Catalyzes with lower
CC efficiency the oxidation of the hydroxyl group at C12 of LTB4 and its
CC derivatives, converting them into biologically less active 12-oxo-LTB4
CC metabolites (By similarity). Reduces 15-oxo-LXA4 to 13,14 dihydro-15-
CC oxo-LXA4, enhancing neutrophil recruitment at the inflammatory site (By
CC similarity). Plays a role in metabolic detoxification of alkenals and
CC ketones. Reduces alpha,beta-unsaturated alkenals and ketones,
CC particularly those with medium-chain length, showing highest affinity
CC toward (2E)-decenal and (3E)-3-nonen-2-one (PubMed:11524419).
CC Inactivates 4-hydroxy-2-nonenal, a cytotoxic lipid constituent of
CC oxidized low-density lipoprotein particles (PubMed:11524419).
CC {ECO:0000250|UniProtKB:Q14914, ECO:0000250|UniProtKB:Q29073,
CC ECO:0000269|PubMed:11524419}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-prostaglandin E1 + NADP(+) = 15-
CC oxoprostaglandin E1 + H(+) + NADPH; Xref=Rhea:RHEA:50584,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57401, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:133408;
CC Evidence={ECO:0000269|PubMed:11524419};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50586;
CC Evidence={ECO:0000305|PubMed:11524419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-prostaglandin E2 + NADP(+) = 15-
CC oxoprostaglandin E2 + H(+) + NADPH; Xref=Rhea:RHEA:11912,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57400, ChEBI:CHEBI:57402,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.48;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11914;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-prostaglandin F1alpha + NADP(+) = 15-
CC oxoprostaglandin F1alpha + H(+) + NADPH; Xref=Rhea:RHEA:50592,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:79072, ChEBI:CHEBI:133411;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50594;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13,14-dihydro-15-oxo-PGF2alpha + NADP(+) = 15-oxoprostaglandin
CC F2alpha + H(+) + NADPH; Xref=Rhea:RHEA:50588, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133374,
CC ChEBI:CHEBI:133409; Evidence={ECO:0000250|UniProtKB:Q14914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50590;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=leukotriene B4 + NADP(+) = 12-oxo-leukotriene B4 + H(+) +
CC NADPH; Xref=Rhea:RHEA:50608, ChEBI:CHEBI:15378, ChEBI:CHEBI:57461,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133309;
CC Evidence={ECO:0000250|UniProtKB:Q29073,
CC ECO:0000250|UniProtKB:Q9EQZ5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50609;
CC Evidence={ECO:0000250|UniProtKB:Q29073,
CC ECO:0000250|UniProtKB:Q9EQZ5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20-hydroxy-leukotriene B4 + NADP(+) = 12-oxo-20-hydroxy-
CC leukotriene B4 + H(+) + NADPH; Xref=Rhea:RHEA:51208,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57460, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:133346;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51209;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-trans-leukotriene B4 + NADP(+) = 12-oxo-(5S)-hydroxy-
CC (6E,8E,10E,14Z)-eicosatetraenoate + H(+) + NADPH;
CC Xref=Rhea:RHEA:51204, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:90723, ChEBI:CHEBI:133974;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51205;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S,12S)-dihydroxy-(6E,10E,12E,14Z)-eicosatetraenoate +
CC NADP(+) = 12-oxo-(5S)-hydroxy-(6E,8E,10E,14Z)-eicosatetraenoate +
CC H(+) + NADPH; Xref=Rhea:RHEA:51212, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133974,
CC ChEBI:CHEBI:133975; Evidence={ECO:0000250|UniProtKB:Q29073};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51213;
CC Evidence={ECO:0000250|UniProtKB:Q29073};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an n-alkanal + NADP(+) = an alk-2-enal + H(+) + NADPH;
CC Xref=Rhea:RHEA:13737, ChEBI:CHEBI:12834, ChEBI:CHEBI:13757,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.74;
CC Evidence={ECO:0000269|PubMed:11524419};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13739;
CC Evidence={ECO:0000305|PubMed:11524419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexanal + NADP(+) = (E)-hex-2-enal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50776, ChEBI:CHEBI:15378, ChEBI:CHEBI:28913,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:88528;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50778;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + octanal = (2E)-octenal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50780, ChEBI:CHEBI:15378, ChEBI:CHEBI:17935,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61748;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50782;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanal + NADP(+) = (2E)-decenal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50612, ChEBI:CHEBI:15378, ChEBI:CHEBI:31457,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133455;
CC Evidence={ECO:0000269|PubMed:11524419};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50614;
CC Evidence={ECO:0000305|PubMed:11524419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanal + NADP(+) = (2E)-dodecenal + H(+) + NADPH;
CC Xref=Rhea:RHEA:50784, ChEBI:CHEBI:15378, ChEBI:CHEBI:27836,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:133741;
CC Evidence={ECO:0000269|PubMed:11524419};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50786;
CC Evidence={ECO:0000305|PubMed:11524419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxynonanal + NADP(+) = (E)-4-hydroxynon-2-enal + H(+) +
CC NADPH; Xref=Rhea:RHEA:64736, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:58968, ChEBI:CHEBI:156112;
CC Evidence={ECO:0000269|PubMed:11524419};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64738;
CC Evidence={ECO:0000305|PubMed:11524419};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + pentan-2-one = (E)-pent-3-en-2-one + H(+) + NADPH;
CC Xref=Rhea:RHEA:50788, ChEBI:CHEBI:15378, ChEBI:CHEBI:16472,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:145276;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50790;
CC Evidence={ECO:0000250|UniProtKB:Q14914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + nonan-2-one = (3E)-nonen-2-one + H(+) + NADPH;
CC Xref=Rhea:RHEA:50616, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:77927, ChEBI:CHEBI:133457;
CC Evidence={ECO:0000269|PubMed:11524419};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:50618;
CC Evidence={ECO:0000305|PubMed:11524419};
CC -!- SUBUNIT: Monomer or homodimer. {ECO:0000250|UniProtKB:Q9EQZ5}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q29073}.
CC -!- INDUCTION: Up-regulated by 1,2-dithiole-3-thione (D3T).
CC {ECO:0000269|PubMed:8968041}.
CC -!- SIMILARITY: Belongs to the NADP-dependent oxidoreductase L4BD family.
CC {ECO:0000305}.
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DR EMBL; U66322; AAB88912.2; -; mRNA.
DR EMBL; BC089775; AAH89775.1; -; mRNA.
DR RefSeq; NP_620218.1; NM_138863.2.
DR AlphaFoldDB; P97584; -.
DR SMR; P97584; -.
DR STRING; 10116.ENSRNOP00000020335; -.
DR BindingDB; P97584; -.
DR ChEMBL; CHEMBL4166; -.
DR iPTMnet; P97584; -.
DR PhosphoSitePlus; P97584; -.
DR jPOST; P97584; -.
DR PaxDb; P97584; -.
DR PRIDE; P97584; -.
DR GeneID; 192227; -.
DR KEGG; rno:192227; -.
DR UCSC; RGD:621195; rat.
DR CTD; 22949; -.
DR RGD; 621195; Ptgr1.
DR VEuPathDB; HostDB:ENSRNOG00000015072; -.
DR eggNOG; KOG1196; Eukaryota.
DR HOGENOM; CLU_026673_29_3_1; -.
DR InParanoid; P97584; -.
DR OMA; GKDKCDY; -.
DR OrthoDB; 884151at2759; -.
DR PhylomeDB; P97584; -.
DR TreeFam; TF324201; -.
DR PRO; PR:P97584; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000015072; Expressed in esophagus and 19 other tissues.
DR Genevisible; P97584; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0036185; F:13-lipoxin reductase activity; ISS:UniProtKB.
DR GO; GO:0036132; F:13-prostaglandin reductase activity; IDA:UniProtKB.
DR GO; GO:0047522; F:15-oxoprostaglandin 13-oxidase activity; IBA:GO_Central.
DR GO; GO:0035798; F:2-alkenal reductase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0097257; F:leukotriene B4 12-hydroxy dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0036102; P:leukotriene B4 metabolic process; ISS:UniProtKB.
DR GO; GO:2001302; P:lipoxin A4 metabolic process; ISS:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD.
DR GO; GO:0097327; P:response to antineoplastic agent; IEP:RGD.
DR CDD; cd08294; leukotriene_B4_DH_like; 1.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR041694; ADH_N_2.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR045010; MDR_fam.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR014190; PTGR1.
DR PANTHER; PTHR43205; PTHR43205; 1.
DR Pfam; PF16884; ADH_N_2; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR02825; B4_12hDH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Fatty acid metabolism; Hydroxylation;
KW Lipid metabolism; NADP; Oxidoreductase; Phosphoprotein;
KW Prostaglandin metabolism; Reference proteome.
FT CHAIN 1..329
FT /note="Prostaglandin reductase 1"
FT /id="PRO_0000218069"
FT BINDING 152..155
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT BINDING 178
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT BINDING 193
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT BINDING 217
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT BINDING 239..245
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT BINDING 270..272
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT BINDING 321
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT MOD_RES 18
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT MOD_RES 178
FT /note="N6-(2-hydroxyisobutyryl)lysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q14914"
FT MOD_RES 178
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91YR9"
SQ SEQUENCE 329 AA; 35718 MW; 8E91165086A05BA9 CRC64;
MVQAKTWTLK KHFEGFPTDS NFELRTTELP PLNNGEVLLE ALFLSVDPYM RVAAKKLKEG
DSMMGEQVAR VVESKNSAFP TGTIVVALLG WTSHSISDGN GLRKLPAEWP DKLPLSLALG
TVGMPGLTAY FGLLDICGLK GGETVLVNAA AGAVGSVVGQ IAKLKGCKVV GTAGSDEKVA
YLKKLGFDVA FNYKTVKSLE EALRTASPDG YDCYFDNVGG EFSNTVILQM KTFGRIAICG
AISQYNRTGP CPPGPSPEVI IYQQLRMEGF IVTRWQGEVR QKALTDLMNW VSEGKIRYHE
YITEGFEKMP AAFMGMLKGD NLGKTIVKA
