UniProt functional annotation for O60760

UniProt code: O60760.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide.
 
Catalytic activity: (5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15- hydroxyprosta-5,13-dienoate = (5Z,13E,15S)-9-alpha,15-dihydroxy- 11-oxoprosta-5,13-dienoate.
Catalytic activity: RX + glutathione = HX + R-S-glutathione.
Cofactor: Glutathione. Required for the prostaglandin D synthase activity.
Enzyme regulation: Prostaglandin PGD2 synthesis is stimulated by calcium and magnesium ions. One calcium or magnesium ion is bound between the subunits of the homodimer. The interactions with the protein are for the most part mediated via water molecules. Magnesium increases the affinity for glutathione, while calcium has no effect on the affinity for glutathione.
Biophysicochemical properties: Kinetic parameters: KM=8 mM for glutathione for the glutathione-conjugating activity; KM=0.6 mM for glutathione for the prostaglandin D synthase activity in the presence of EDTA; KM=0.14 mM for glutathione for the prostaglandin D synthase activity in the presence of magnesium ions; Vmax=8.6 umol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate; Vmax=5.1 umol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate; Vmax=44.3 umol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate; Vmax=10.7 umol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate; Vmax=6.8 umol/min/mg enzyme with allyl isothiocyanate as substrate; Vmax=6.3 umol/min/mg enzyme with benzyl isothiocyanate as substrate; Vmax=0.05 umol/min/mg enzyme with cumene hydroperoxide as substrate;
Subunit: Homodimer.
Subcellular location: Cytoplasm.
Tissue specificity: Expressed in a number of megakaryocytic cell lines but not in platelets. Highly expressed in adipose tissue, macrophages and placenta. Also expressed at lower levels in lung, heart, lymph nodes, appendix, bone marrow and fetal liver.
Developmental stage: Highest levels in immature megakaryocytic cells. Disappears after final differentiation to platelets.
Induction: By 12-O-tetradecanoylphorbol-13-acetate (TPA).
Similarity: Belongs to the GST superfamily. Sigma family.
Similarity: Contains 1 GST C-terminal domain.
Similarity: Contains 1 GST N-terminal domain.

Annotations taken from UniProtKB at the EBI.