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   27-MAR-2024, entry version 175.
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   PhosphoSitePlus; O35543; -.
DR   PaxDb; 10116-ENSRNOP00000008826; -.
DR   Ensembl; ENSRNOT00000008826.6; ENSRNOP00000008826.3; ENSRNOG00000006583.6.
DR   Ensembl; ENSRNOT00055024716; ENSRNOP00055020197; ENSRNOG00055014398.
DR   Ensembl; ENSRNOT00060037634; ENSRNOP00060031027; ENSRNOG00060021729.
DR   Ensembl; ENSRNOT00065051465; ENSRNOP00065042379; ENSRNOG00065029784.
DR   GeneID; 58962; -.
DR   KEGG; rno:58962; -.
DR   UCSC; RGD:69251; rat.
DR   AGR; RGD:69251; -.
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; ENEWFIG; -.
DR   OrthoDB; 1385810at2759; -.
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 cell types or tissues.
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; IEA:UniProtKB-EC.
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: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   CDD; cd10295; GST_C_Sigma; 1.
DR   CDD; cd03039; GST_N_Sigma_like; 1.
DR   Gene3D; 1.20.1050.10; -; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
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   PANTHER; PTHR11571; GLUTATHIONE S-TRANSFERASE; 1.
DR   PANTHER; PTHR11571:SF224; HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE; 1.
DR   Pfam; PF14497; GST_C_3; 1.
DR   Pfam; PF02798; GST_N; 1.
DR   SFLD; SFLDG01205; AMPS.1; 1.
DR   SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR   SUPFAM; SSF47616; GST C-terminal domain-like; 1.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS50405; GST_CTER; 1.
DR   PROSITE; PS50404; GST_NTER; 1.
DR   Genevisible; O35543; RN.
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
//