HPGDS_RAT
ID HPGDS_RAT Reviewed; 199 AA.
AC O35543; O35351;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Hematopoietic prostaglandin D synthase;
DE Short=H-PGDS;
DE EC=5.3.99.2 {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:9323136};
DE AltName: Full=GST class-sigma;
DE AltName: Full=Glutathione S-transferase;
DE EC=2.5.1.18 {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:9323136};
DE AltName: Full=Glutathione-dependent PGD synthase;
DE AltName: Full=Glutathione-requiring prostaglandin D synthase;
DE AltName: Full=Prostaglandin-H2 D-isomerase;
GN Name=Hpgds {ECO:0000312|RGD:69251}; Synonyms=Gsts, Pgds, Ptgds2;
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], X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN
RP COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Spleen;
RX PubMed=9323136; DOI=10.1016/s0092-8674(00)80374-8;
RA Kanaoka Y., Ago H., Inagaki E., Nanayama T., Miyano M., Kikuno R.,
RA Fujii Y., Eguchi N., Toh H., Urade Y., Hayaishi O.;
RT "Cloning and crystal structure of hematopoietic prostaglandin D synthase.";
RL Cell 90:1085-1095(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
RX PubMed=11672424; DOI=10.1042/0264-6021:3590507;
RA Jowsey I.R., Thomson A.M., Flanagan J.U., Murdock P.R., Moore G.B.,
RA Meyer D.J., Murphy G.J., Smith S.A., Hayes J.D.;
RT "Mammalian class Sigma glutathione S-transferases: catalytic properties and
RT tissue-specific expression of human and rat GSH-dependent prostaglandin D2
RT synthases.";
RL Biochem. J. 359:507-516(2001).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 39-198.
RC STRAIN=Sprague-Dawley; TISSUE=Spleen;
RA Yuan Y., Reddy R.G., Kim H.;
RT "Purification and cloning of rat glutathione-dependent prostaglandin D
RT synthase.";
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-8; ARG-14; TRP-104; LYS-112; TYR-152; CYS-156; LYS-198
RP AND LEU-199.
RX PubMed=10871602; DOI=10.1074/jbc.m000750200;
RA Pinzar E., Miyano M., Kanaoka Y., Urade Y., Hayaishi O.;
RT "Structural basis of hematopoietic prostaglandin D synthase activity
RT elucidated by site-directed mutagenesis.";
RL J. Biol. Chem. 275:31239-31244(2000).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16547010; DOI=10.1074/jbc.m506431200;
RA Aritake K., Kado Y., Inoue T., Miyano M., Urade Y.;
RT "Structural and functional characterization of HQL-79, an orally selective
RT inhibitor of human hematopoietic prostaglandin D synthase.";
RL J. Biol. Chem. 281:15277-15286(2006).
CC -!- FUNCTION: Bifunctional enzyme which catalyzes both the conversion of
CC PGH2 to PGD2, a prostaglandin involved in smooth muscle
CC contraction/relaxation and a potent inhibitor of platelet aggregation,
CC and the conjugation of glutathione with a wide range of aryl halides
CC and organic isothiocyanates. Also exhibits low glutathione-peroxidase
CC activity towards cumene hydroperoxide. {ECO:0000269|PubMed:10871602,
CC ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:16547010,
CC ECO:0000269|PubMed:9323136}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = prostaglandin D2; Xref=Rhea:RHEA:10600,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:57406; EC=5.3.99.2;
CC Evidence={ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424,
CC ECO:0000269|PubMed:16547010, ECO:0000269|PubMed:9323136};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10601;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutathione + RX = a halide anion + an S-substituted
CC glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:90779; EC=2.5.1.18;
CC Evidence={ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424,
CC ECO:0000269|PubMed:9323136};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-glyceryl-prostaglandin H2 = 2-glyceryl-prostaglandin D2;
CC Xref=Rhea:RHEA:51232, ChEBI:CHEBI:85166, ChEBI:CHEBI:133979;
CC Evidence={ECO:0000250|UniProtKB:O60760};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51233;
CC Evidence={ECO:0000250|UniProtKB:O60760};
CC -!- COFACTOR:
CC Name=glutathione; Xref=ChEBI:CHEBI:57925;
CC Evidence={ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Note=Glutathione is required for the prostaglandin D synthase activity.
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100 uM for glutathione for the prostaglandin D synthase activity
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC KM=500 uM for glutathione for the glutathione-conjugating activity
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC KM=500 uM for PGH2 for the prostaglandin D synthase activity
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC KM=3 mM for 1-chloro-2,4-dinitrobenzene {ECO:0000269|PubMed:10871602,
CC ECO:0000269|PubMed:11672424};
CC Vmax=17.6 umol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as
CC substrate {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Vmax=9.2 umol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as
CC substrate {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Vmax=48.3 umol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as
CC substrate {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Vmax=17.9 umol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as
CC substrate {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Vmax=0.35 umol/min/mg enzyme with cumene hydroperoxide as substrate
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Vmax=10.2 umol/min/mg enzyme with allyl isothiocyanate as substrate
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC Vmax=11.3 umol/min/mg enzyme with benzyl isothiocyanate as substrate
CC {ECO:0000269|PubMed:10871602, ECO:0000269|PubMed:11672424};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:9323136}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen and bone marrow. Lower
CC levels of expression in small intestine, colon, liver, pancreas and
CC skin. Not detected in brain, heart, lung or kidney (at protein level).
CC {ECO:0000269|PubMed:11672424, ECO:0000269|PubMed:9323136}.
CC -!- SIMILARITY: Belongs to the GST superfamily. Sigma family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB72099.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D82071; BAA22898.1; -; mRNA.
DR EMBL; BC087590; AAH87590.1; -; mRNA.
DR EMBL; AF021882; AAB72099.1; ALT_FRAME; mRNA.
DR RefSeq; NP_113832.1; NM_031644.2.
DR PDB; 1PD2; X-ray; 2.30 A; 1/2=1-199.
DR PDB; 5Y9Z; X-ray; 1.09 A; A/B=1-199.
DR PDB; 6N69; X-ray; 2.00 A; A/B=1-199.
DR PDBsum; 1PD2; -.
DR PDBsum; 5Y9Z; -.
DR PDBsum; 6N69; -.
DR AlphaFoldDB; O35543; -.
DR SMR; O35543; -.
DR STRING; 10116.ENSRNOP00000008826; -.
DR BindingDB; O35543; -.
DR ChEMBL; CHEMBL4523131; -.
DR PaxDb; O35543; -.
DR Ensembl; ENSRNOT00000008826; ENSRNOP00000008826; ENSRNOG00000006583.
DR GeneID; 58962; -.
DR KEGG; rno:58962; -.
DR UCSC; RGD:69251; rat.
DR CTD; 27306; -.
DR RGD; 69251; Hpgds.
DR eggNOG; KOG1695; Eukaryota.
DR GeneTree; ENSGT00940000160278; -.
DR HOGENOM; CLU_039475_1_0_1; -.
DR InParanoid; O35543; -.
DR OMA; TEMEQCH; -.
DR OrthoDB; 1162336at2759; -.
DR PhylomeDB; O35543; -.
DR TreeFam; TF105321; -.
DR BRENDA; 5.3.99.2; 5301.
DR Reactome; R-RNO-156590; Glutathione conjugation.
DR Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR SABIO-RK; O35543; -.
DR EvolutionaryTrace; O35543; -.
DR PRO; PR:O35543; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000006583; Expressed in spleen and 15 other tissues.
DR Genevisible; O35543; RN.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0004667; F:prostaglandin-D synthase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0006749; P:glutathione metabolic process; IBA:GO_Central.
DR GO; GO:2000255; P:negative regulation of male germ cell proliferation; ISO:RGD.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; TAS:RGD.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISS:UniProtKB.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR040079; Glutathione_S-Trfase.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR004046; GST_C.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF14497; GST_C_3; 1.
DR Pfam; PF02798; GST_N; 1.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS50405; GST_CTER; 1.
DR PROSITE; PS50404; GST_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism;
KW Isomerase; Lipid biosynthesis; Lipid metabolism;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Transferase.
FT CHAIN 1..199
FT /note="Hematopoietic prostaglandin D synthase"
FT /id="PRO_0000185936"
FT DOMAIN 2..79
FT /note="GST N-terminal"
FT DOMAIN 81..199
FT /note="GST C-terminal"
FT BINDING 8
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:9323136"
FT BINDING 14
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:9323136"
FT BINDING 39
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:9323136"
FT BINDING 49..51
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:9323136"
FT BINDING 63..64
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:9323136"
FT MUTAGEN 8
FT /note="Y->F: Moderate reduction of protein expression
FT levels. Abolishes both prostaglandin D synthase and
FT glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 14
FT /note="R->E: Moderate reduction of protein expression
FT levels. Abolishes both prostaglandin D synthase and
FT glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 14
FT /note="R->K: Moderate reduction of protein expression
FT levels. Abolishes both prostaglandin D synthase and
FT glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 104
FT /note="W->I: No significant effect on protein expression
FT levels. Abolishes both prostaglandin D synthase and
FT glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 112
FT /note="K->E: Significant reduction of protein expression
FT levels. Significantly reduces prostaglandin D synthase and
FT moderately reduces glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 152
FT /note="Y->F: Significant reduction of protein expression
FT levels. Moderately reduces prostaglandin D synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 156
FT /note="C->L: No significant effect on protein expression
FT levels. Abolishes prostaglandin D synthase and
FT significantly reduces glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 156
FT /note="C->Y: Significant reduction of protein expression
FT levels. Abolishes prostaglandin D synthase and
FT significantly reduces glutathione-conjugating activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 198
FT /note="K->E: Moderate reduction of protein expression
FT levels. No significant effect on catalytic activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT MUTAGEN 199
FT /note="L->F: Moderate reduction of protein expression
FT levels. No significant effect on catalytic activities."
FT /evidence="ECO:0000269|PubMed:10871602"
FT CONFLICT 194
FT /note="R -> S (in Ref. 4; AAB72099)"
FT /evidence="ECO:0000305"
FT STRAND 5..12
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT STRAND 59..62
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 82..99
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 109..121
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 124..135
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 148..163
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT TURN 165..170
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:5Y9Z"
FT HELIX 185..193
FT /evidence="ECO:0007829|PDB:5Y9Z"
SQ SEQUENCE 199 AA; 23297 MW; E5EF934D89DC240F CRC64;
MPNYKLLYFN MRGRAEIIRY IFAYLDIKYE DHRIEQADWP KIKPTLPFGK IPVLEVEGLT
LHQSLAIARY LTKNTDLAGK TELEQCQVDA VVDTLDDFMS LFPWAEENQD LKERTFNDLL
TRQAPHLLKD LDTYLGDKEW FIGNYVTWAD FYWDICSTTL LVLKPDLLGI YPRLVSLRNK
VQAIPAISAW ILKRPQTKL
