UniProt functional annotation for P08263



	UniProt functional annotation for P08263

UniProt code: P08263.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (Probable). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene- 3,17-dione and may therefore play an important role in hormone biosynthesis (PubMed:11152686). Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)- hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid (PubMed:16624487). {ECO:0000269|PubMed:11152686, ECO:0000269|PubMed:16624487, ECO:0000269|PubMed:9084911, ECO:0000305|PubMed:20606271}.

Catalytic activity: Reaction=glutathione + RX = a halide anion + an S-substituted glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378, ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925, ChEBI:CHEBI:90779; EC=2.5.1.18; Evidence={ECO:0000269|PubMed:20606271}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438; Evidence={ECO:0000305|PubMed:20606271};

Catalytic activity: Reaction=glutathione + prostaglandin A2 = prostaglandin A2-S-(R)- glutathione; Xref=Rhea:RHEA:50796, ChEBI:CHEBI:57925, ChEBI:CHEBI:133370, ChEBI:CHEBI:133768; Evidence={ECO:0000269|PubMed:9084911}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50797; Evidence={ECO:0000305|PubMed:9084911};

Catalytic activity: Reaction=glutathione + prostaglandin J2 = prostaglandin J2-S-(R)- glutathione; Xref=Rhea:RHEA:50804, ChEBI:CHEBI:57925, ChEBI:CHEBI:133396, ChEBI:CHEBI:133771; Evidence={ECO:0000269|PubMed:9084911}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50805; Evidence={ECO:0000305|PubMed:9084911};

Catalytic activity: Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850; Evidence={ECO:0000269|PubMed:16624487}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889; Evidence={ECO:0000305|PubMed:16624487};

Catalytic activity: Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione; Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865; Evidence={ECO:0000269|PubMed:11152686}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937; Evidence={ECO:0000305|PubMed:11152686};

Activity regulation: The isomerase activity is inhibited by S- methylglutathione (GSMe). {ECO:0000269|PubMed:11152686}.

Biophysicochemical properties: Kinetic parameters: KM=160 uM for prostaglandin A2 (at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:9084911}; KM=160 uM for glutathione (at pH 8.0) {ECO:0000269|PubMed:11152686}; KM=58 uM for androst-5-ene-3,17-dione (at pH 8.0) {ECO:0000269|PubMed:11152686}; Vmax=121 nmol/min/mg enzyme for the formation of the glutathione-S- conjugate of prostaglandin A2 (at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:9084911}; Vmax=40 umol/min/mg enzyme for the isomerization of androst-5-ene- 3,17-dione (at pH 8.0) {ECO:0000269|PubMed:11152686}; Note=kcat is 29.3 sec(-1) for the isomerization of androst-5-ene- 3,17-dione. {ECO:0000269|PubMed:11152686}; pH dependence: Optimum pH is 8.0 for the isomerization of androst-5-ene-3,17-dione. {ECO:0000269|PubMed:11152686};

Subunit: Homodimer or heterodimer of GSTA1 and GSTA2. {ECO:0000269|PubMed:12211029, ECO:0000269|PubMed:15333749, ECO:0000269|PubMed:15893769, ECO:0000269|PubMed:16421451, ECO:0000269|PubMed:19618965, ECO:0000269|PubMed:20606271, ECO:0000269|PubMed:8331657, ECO:0000269|PubMed:8591048}.

Subcellular location: Cytoplasm.

Tissue specificity: Liver.

Domain: The C-terminal domain may form a component of the hydrophobic substrate-binding site, but in contrast appears not to be directly involved in GSH binding and is not absolutely essential for catalytic activity.

Similarity: Belongs to the GST superfamily. Alpha family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (Probable). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene- 3,17-dione and may therefore play an important role in hormone biosynthesis (PubMed:11152686). Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)- hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid (PubMed:16624487). {ECO:0000269\|PubMed:11152686, ECO:0000269\|PubMed:16624487, ECO:0000269\|PubMed:9084911, ECO:0000305\|PubMed:20606271}.


Catalytic activity:		Reaction=glutathione + RX = a halide anion + an S-substituted glutathione + H(+); Xref=Rhea:RHEA:16437, ChEBI:CHEBI:15378, ChEBI:CHEBI:16042, ChEBI:CHEBI:17792, ChEBI:CHEBI:57925, ChEBI:CHEBI:90779; EC=2.5.1.18; Evidence={ECO:0000269\|PubMed:20606271}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16438; Evidence={ECO:0000305\|PubMed:20606271};
Catalytic activity:		Reaction=glutathione + prostaglandin A2 = prostaglandin A2-S-(R)- glutathione; Xref=Rhea:RHEA:50796, ChEBI:CHEBI:57925, ChEBI:CHEBI:133370, ChEBI:CHEBI:133768; Evidence={ECO:0000269\|PubMed:9084911}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50797; Evidence={ECO:0000305\|PubMed:9084911};
Catalytic activity:		Reaction=glutathione + prostaglandin J2 = prostaglandin J2-S-(R)- glutathione; Xref=Rhea:RHEA:50804, ChEBI:CHEBI:57925, ChEBI:CHEBI:133396, ChEBI:CHEBI:133771; Evidence={ECO:0000269\|PubMed:9084911}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50805; Evidence={ECO:0000305\|PubMed:9084911};
Catalytic activity:		Reaction=(13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O; Xref=Rhea:RHEA:48888, ChEBI:CHEBI:15377, ChEBI:CHEBI:57466, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297, ChEBI:CHEBI:90850; Evidence={ECO:0000269\|PubMed:16624487}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48889; Evidence={ECO:0000305\|PubMed:16624487};
Catalytic activity:		Reaction=androst-5-ene-3,17-dione = androst-4-ene-3,17-dione; Xref=Rhea:RHEA:43936, ChEBI:CHEBI:16422, ChEBI:CHEBI:83865; Evidence={ECO:0000269\|PubMed:11152686}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43937; Evidence={ECO:0000305\|PubMed:11152686};
Activity regulation:		The isomerase activity is inhibited by S- methylglutathione (GSMe). {ECO:0000269\|PubMed:11152686}.
Biophysicochemical properties:		Kinetic parameters: KM=160 uM for prostaglandin A2 (at pH 7.0 and 37 degrees Celsius) {ECO:0000269\|PubMed:9084911}; KM=160 uM for glutathione (at pH 8.0) {ECO:0000269\|PubMed:11152686}; KM=58 uM for androst-5-ene-3,17-dione (at pH 8.0) {ECO:0000269\|PubMed:11152686}; Vmax=121 nmol/min/mg enzyme for the formation of the glutathione-S- conjugate of prostaglandin A2 (at pH 7.0 and 37 degrees Celsius) {ECO:0000269\|PubMed:9084911}; Vmax=40 umol/min/mg enzyme for the isomerization of androst-5-ene- 3,17-dione (at pH 8.0) {ECO:0000269\|PubMed:11152686}; Note=kcat is 29.3 sec(-1) for the isomerization of androst-5-ene- 3,17-dione. {ECO:0000269\|PubMed:11152686}; pH dependence: Optimum pH is 8.0 for the isomerization of androst-5-ene-3,17-dione. {ECO:0000269\|PubMed:11152686};
Subunit:		Homodimer or heterodimer of GSTA1 and GSTA2. {ECO:0000269\|PubMed:12211029, ECO:0000269\|PubMed:15333749, ECO:0000269\|PubMed:15893769, ECO:0000269\|PubMed:16421451, ECO:0000269\|PubMed:19618965, ECO:0000269\|PubMed:20606271, ECO:0000269\|PubMed:8331657, ECO:0000269\|PubMed:8591048}.
Subcellular location:		Cytoplasm.
Tissue specificity:		Liver.
Domain:		The C-terminal domain may form a component of the hydrophobic substrate-binding site, but in contrast appears not to be directly involved in GSH binding and is not absolutely essential for catalytic activity.
Similarity:		Belongs to the GST superfamily. Alpha family. {ECO:0000305}.