UniProtKB - P08263 (GSTA1_HUMAN)
Protein
Glutathione S-transferase A1
Gene
GSTA1
Organism
Homo sapiens (Human)
Status
Functioni
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).1 Publication3 Publications
Catalytic activityi
- EC:2.5.1.181 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- (13S)-hydroperoxy-(9Z,11E)-octadecadienoate + 2 glutathione = (13S)-hydroxy-(9Z,11E)-octadecadienoate + glutathione disulfide + H2O1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Activity regulationi
The isomerase activity is inhibited by S-methylglutathione (GSMe).1 Publication
Kineticsi
kcat is 29.3 sec(-1) for the isomerization of androst-5-ene-3,17-dione.1 Publication
- KM=160 µM for prostaglandin A2 (at pH 7.0 and 37 degrees Celsius)1 Publication
- KM=160 µM for glutathione (at pH 8.0)1 Publication
- KM=58 µM for androst-5-ene-3,17-dione (at pH 8.0)1 Publication
- 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)1 Publication
- Vmax=40 µmol/min/mg enzyme for the isomerization of androst-5-ene-3,17-dione (at pH 8.0)1 Publication
pH dependencei
Optimum pH is 8.0 for the isomerization of androst-5-ene-3,17-dione.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 9 | Glutathione2 Publications | 1 | |
Binding sitei | 45 | Glutathione2 Publications | 1 |
GO - Molecular functioni
- fatty acid binding Source: BHF-UCL
- glutathione peroxidase activity Source: BHF-UCL
- glutathione transferase activity Source: UniProtKB
- steroid delta-isomerase activity Source: UniProtKB
GO - Biological processi
- epithelial cell differentiation Source: UniProtKB
- glutathione derivative biosynthetic process Source: UniProtKB
- glutathione metabolic process Source: UniProtKB
- linoleic acid metabolic process Source: BHF-UCL
- prostaglandin metabolic process Source: UniProtKB
- xenobiotic metabolic process Source: GO_Central
Keywordsi
Molecular function | Isomerase, Oxidoreductase, Peroxidase, Transferase |
Enzyme and pathway databases
BioCyci | MetaCyc:G66-32542-MONOMER |
BRENDAi | 2.5.1.18, 2681 |
PathwayCommonsi | P08263 |
Reactomei | R-HSA-156590, Glutathione conjugation R-HSA-189483, Heme degradation |
SABIO-RKi | P08263 |
SIGNORi | P08263 |
Chemistry databases
SwissLipidsi | SLP:000001476 |
Names & Taxonomyi
Protein namesi | Recommended name: Glutathione S-transferase A12 Publications (EC:2.5.1.181 Publication)Alternative name(s): 13-hydroperoxyoctadecadienoate peroxidase1 Publication (EC:1.11.1.-1 Publication) Androst-5-ene-3,17-dione isomerase1 Publication (EC:5.3.3.-1 Publication) GST HA subunit 1 GST class-alpha member 1 GST-epsilon GSTA1-1 GTH1 Cleaved into the following chain: |
Gene namesi | Name:GSTA1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000243955.5 |
HGNCi | HGNC:4626, GSTA1 |
MIMi | 138359, gene |
neXtProti | NX_P08263 |
Subcellular locationi
Other locations
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 9 | Y → F: Decreased isomerase activity. 1 Publication | 1 | |
Mutagenesisi | 71 | I → A or V: No significant effect on enzyme activity. Reduces protein stability. 1 Publication | 1 | |
Mutagenesisi | 216 | A → H: Confers ability to hydrolyze S-glutathionyl benzoate to glutathione and benzoic acid. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2938 |
OpenTargetsi | ENSG00000243955 |
PharmGKBi | PA29016 |
Miscellaneous databases
Pharosi | P08263, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3409 |
DrugBanki | DB02486, 2-Hydroxyethyl Disulfide DB00993, Azathioprine DB01008, Busulfan DB11672, Curcumin DB00143, Glutathione DB03310, Glutathione disulfide DB03003, Glutathione sulfonic acid DB13014, Hypericin DB02943, N-(4-Aminobutanoyl)-S-(4-methoxybenzyl)-L-cysteinylglycine DB03602, S-benzylglutathione DB04132, S-Hexylglutathione DB01915, S-Hydroxycysteine |
DrugCentrali | P08263 |
Polymorphism and mutation databases
BioMutai | GSTA1 |
DMDMi | 121730 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000423203 | 1 – 222 | Glutathione S-transferase A1Add BLAST | 222 | |
Initiator methioninei | Removed; alternateBy similarity1 Publication | |||
ChainiPRO_0000185783 | 2 – 222 | Glutathione S-transferase A1, N-terminally processedAdd BLAST | 221 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineBy similarity | 1 | |
Modified residuei | 2 | N-acetylalanine; in Glutathione S-transferase A1, N-terminally processedBy similarity | 1 | |
Modified residuei | 4 | N6-succinyllysineBy similarity | 1 |
Keywords - PTMi
AcetylationProteomic databases
jPOSTi | P08263 |
MassIVEi | P08263 |
MaxQBi | P08263 |
PaxDbi | P08263 |
PeptideAtlasi | P08263 |
PRIDEi | P08263 |
ProteomicsDBi | 12637 52103 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00657682 |
PTM databases
iPTMneti | P08263 |
PhosphoSitePlusi | P08263 |
Expressioni
Tissue specificityi
Liver.
Gene expression databases
Bgeei | ENSG00000243955, Expressed in nephron tubule and 163 other tissues |
ExpressionAtlasi | P08263, baseline and differential |
Genevisiblei | P08263, HS |
Organism-specific databases
HPAi | ENSG00000243955, Group enriched (adrenal gland, intestine, kidney, liver, testis) |
Interactioni
Subunit structurei
Homodimer or heterodimer of GSTA1 and GSTA2.
8 PublicationsProtein-protein interaction databases
BioGRIDi | 109193, 15 interactors |
IntActi | P08263, 12 interactors |
STRINGi | 9606.ENSP00000335620 |
Chemistry databases
BindingDBi | P08263 |
Miscellaneous databases
RNActi | P08263, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P08263 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P08263 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 3 – 83 | GST N-terminalAdd BLAST | 81 | |
Domaini | 85 – 207 | GST C-terminalAdd BLAST | 123 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 54 – 55 | Glutathione binding2 Publications | 2 | |
Regioni | 67 – 68 | Glutathione binding2 Publications | 2 |
Domaini
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.
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1695, Eukaryota |
GeneTreei | ENSGT00940000164034 |
HOGENOMi | CLU_039475_4_0_1 |
InParanoidi | P08263 |
OMAi | FIEQPED |
PhylomeDBi | P08263 |
TreeFami | TF105321 |
Family and domain databases
DisProti | DP01506 |
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR010987, Glutathione-S-Trfase_C-like IPR036282, Glutathione-S-Trfase_C_sf IPR040079, Glutathione_S-Trfase IPR004045, Glutathione_S-Trfase_N IPR003080, GST_alpha IPR004046, GST_C IPR036249, Thioredoxin-like_sf |
Pfami | View protein in Pfam PF00043, GST_C, 1 hit PF02798, GST_N, 1 hit |
PRINTSi | PR01266, GSTRNSFRASEA |
SFLDi | SFLDS00019, Glutathione_Transferase_(cytos, 1 hit |
SUPFAMi | SSF47616, SSF47616, 1 hit SSF52833, SSF52833, 1 hit |
PROSITEi | View protein in PROSITE PS50405, GST_CTER, 1 hit PS50404, GST_NTER, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P08263-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAEKPKLHYF NARGRMESTR WLLAAAGVEF EEKFIKSAED LDKLRNDGYL
60 70 80 90 100
MFQQVPMVEI DGMKLVQTRA ILNYIASKYN LYGKDIKERA LIDMYIEGIA
110 120 130 140 150
DLGEMILLLP VCPPEEKDAK LALIKEKIKN RYFPAFEKVL KSHGQDYLVG
160 170 180 190 200
NKLSRADIHL VELLYYVEEL DSSLISSFPL LKALKTRISN LPTVKKFLQP
210 220
GSPRKPPMDE KSLEEARKIF RF
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 18 | S → C in AAA36174 (PubMed:3678589).Curated | 1 | |
Sequence conflicti | 51 | M → T in AAT06769 (Ref. 7) Curated | 1 | |
Sequence conflicti | 56 – 58 | PMV → AML in AAA36174 (PubMed:3678589).Curated | 3 | |
Sequence conflicti | 212 | S → L AA sequence (PubMed:2604726).Curated | 1 | |
Sequence conflicti | 216 | A → S AA sequence (PubMed:8431482).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_033978 | 19 | T → I. Corresponds to variant dbSNP:rs1051578Ensembl. | 1 | |
Natural variantiVAR_049482 | 113 | P → Q. Corresponds to variant dbSNP:rs1051745Ensembl. | 1 | |
Natural variantiVAR_049483 | 117 | K → Q. Corresponds to variant dbSNP:rs1051757Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15872 mRNA Translation: AAA70226.1 M21758 mRNA Translation: AAA52615.1 M25627 mRNA Translation: AAA36174.1 M14777 mRNA Translation: AAA52618.1 S76235 , S76221, S76223, S76225, S76228, S76232 Genomic DNA Translation: AAB20973.1 S49975 mRNA Translation: AAB24012.1 AY532928 mRNA Translation: AAT06769.1 CR407656 mRNA Translation: CAG28584.1 AL590363 Genomic DNA No translation available. CH471081 Genomic DNA Translation: EAX04385.1 BC053578 mRNA Translation: AAH53578.1 BC110891 mRNA Translation: AAI10892.1 |
CCDSi | CCDS4945.1 |
PIRi | A25909, A56666 S29657 |
RefSeqi | NP_665683.1, NM_145740.4 |
Genome annotation databases
Ensembli | ENST00000334575; ENSP00000335620; ENSG00000243955 |
GeneIDi | 2938 |
KEGGi | hsa:2938 |
UCSCi | uc003paz.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15872 mRNA Translation: AAA70226.1 M21758 mRNA Translation: AAA52615.1 M25627 mRNA Translation: AAA36174.1 M14777 mRNA Translation: AAA52618.1 S76235 , S76221, S76223, S76225, S76228, S76232 Genomic DNA Translation: AAB20973.1 S49975 mRNA Translation: AAB24012.1 AY532928 mRNA Translation: AAT06769.1 CR407656 mRNA Translation: CAG28584.1 AL590363 Genomic DNA No translation available. CH471081 Genomic DNA Translation: EAX04385.1 BC053578 mRNA Translation: AAH53578.1 BC110891 mRNA Translation: AAI10892.1 |
CCDSi | CCDS4945.1 |
PIRi | A25909, A56666 S29657 |
RefSeqi | NP_665683.1, NM_145740.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1GSD | X-ray | 2.50 | A/B/C/D | 2-222 | [»] | |
1GSE | X-ray | 2.00 | A/B | 2-222 | [»] | |
1GSF | X-ray | 2.70 | A/B/C/D | 2-222 | [»] | |
1GUH | X-ray | 2.60 | A/B/C/D | 2-222 | [»] | |
1K3L | X-ray | 1.50 | A/B | 2-222 | [»] | |
1K3O | X-ray | 1.80 | A/B | 2-222 | [»] | |
1K3Y | X-ray | 1.30 | A/B | 2-222 | [»] | |
1LBK | X-ray | 1.86 | A/B | 208-213 | [»] | |
1PKW | X-ray | 2.00 | A/B | 1-222 | [»] | |
1PKZ | X-ray | 2.10 | A/B | 1-222 | [»] | |
1PL1 | X-ray | 1.75 | A/B | 1-222 | [»] | |
1PL2 | X-ray | 1.80 | A/B | 1-222 | [»] | |
1USB | X-ray | 2.07 | A/B | 2-222 | [»] | |
1XWG | X-ray | 1.85 | A/B | 2-222 | [»] | |
1YDK | X-ray | 1.95 | A/B | 1-222 | [»] | |
2R3X | X-ray | 1.80 | A/B | 1-222 | [»] | |
2R6K | X-ray | 2.51 | A/B | 1-222 | [»] | |
3I69 | X-ray | 2.38 | A/B/C/D/E/F/G/H | 1-222 | [»] | |
3I6A | X-ray | 1.98 | A/B/C/D/E/F/G/H | 1-222 | [»] | |
3IK9 | X-ray | 2.20 | A/B/C/D/E/F/G/H | 1-222 | [»] | |
3KTL | X-ray | 1.75 | A/B | 2-222 | [»] | |
3L0H | X-ray | 2.13 | A/B | 1-222 | [»] | |
3Q74 | X-ray | 1.79 | A/B | 2-222 | [»] | |
3U6V | X-ray | 2.20 | A/B | 1-222 | [»] | |
3ZFB | X-ray | 1.86 | A/B | 1-222 | [»] | |
3ZFL | X-ray | 1.88 | A/B | 1-222 | [»] | |
4HJ2 | X-ray | 2.10 | A/B | 4-220 | [»] | |
5JCU | X-ray | 1.93 | A/B/C/D | 2-222 | [»] | |
5LCZ | X-ray | 2.33 | A/B | 1-100 | [»] | |
A/B | 201-222 | [»] | ||||
5LD0 | X-ray | 1.60 | A | 1-85 | [»] | |
A | 214-222 | [»] | ||||
6ATO | X-ray | 1.55 | A/B | 2-222 | [»] | |
6ATP | X-ray | 1.70 | A/B | 2-222 | [»] | |
6ATQ | X-ray | 2.00 | A/B | 2-222 | [»] | |
6ATR | X-ray | 1.29 | A/B | 2-222 | [»] | |
6YAW | X-ray | 2.19 | A/B | 1-222 | [»] | |
SMRi | P08263 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109193, 15 interactors |
IntActi | P08263, 12 interactors |
STRINGi | 9606.ENSP00000335620 |
Chemistry databases
BindingDBi | P08263 |
ChEMBLi | CHEMBL3409 |
DrugBanki | DB02486, 2-Hydroxyethyl Disulfide DB00993, Azathioprine DB01008, Busulfan DB11672, Curcumin DB00143, Glutathione DB03310, Glutathione disulfide DB03003, Glutathione sulfonic acid DB13014, Hypericin DB02943, N-(4-Aminobutanoyl)-S-(4-methoxybenzyl)-L-cysteinylglycine DB03602, S-benzylglutathione DB04132, S-Hexylglutathione DB01915, S-Hydroxycysteine |
DrugCentrali | P08263 |
SwissLipidsi | SLP:000001476 |
PTM databases
iPTMneti | P08263 |
PhosphoSitePlusi | P08263 |
Polymorphism and mutation databases
BioMutai | GSTA1 |
DMDMi | 121730 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00657682 |
Proteomic databases
jPOSTi | P08263 |
MassIVEi | P08263 |
MaxQBi | P08263 |
PaxDbi | P08263 |
PeptideAtlasi | P08263 |
PRIDEi | P08263 |
ProteomicsDBi | 12637 52103 |
Protocols and materials databases
Antibodypediai | 30937, 472 antibodies |
DNASUi | 2938 |
Genome annotation databases
Ensembli | ENST00000334575; ENSP00000335620; ENSG00000243955 |
GeneIDi | 2938 |
KEGGi | hsa:2938 |
UCSCi | uc003paz.4, human |
Organism-specific databases
CTDi | 2938 |
DisGeNETi | 2938 |
EuPathDBi | HostDB:ENSG00000243955.5 |
GeneCardsi | GSTA1 |
HGNCi | HGNC:4626, GSTA1 |
HPAi | ENSG00000243955, Group enriched (adrenal gland, intestine, kidney, liver, testis) |
MIMi | 138359, gene |
neXtProti | NX_P08263 |
OpenTargetsi | ENSG00000243955 |
PharmGKBi | PA29016 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1695, Eukaryota |
GeneTreei | ENSGT00940000164034 |
HOGENOMi | CLU_039475_4_0_1 |
InParanoidi | P08263 |
OMAi | FIEQPED |
PhylomeDBi | P08263 |
TreeFami | TF105321 |
Enzyme and pathway databases
BioCyci | MetaCyc:G66-32542-MONOMER |
BRENDAi | 2.5.1.18, 2681 |
PathwayCommonsi | P08263 |
Reactomei | R-HSA-156590, Glutathione conjugation R-HSA-189483, Heme degradation |
SABIO-RKi | P08263 |
SIGNORi | P08263 |
Miscellaneous databases
BioGRID-ORCSi | 2938, 5 hits in 817 CRISPR screens |
ChiTaRSi | GSTA1, human |
EvolutionaryTracei | P08263 |
GeneWikii | Glutathione_S-transferase_A1 |
GenomeRNAii | 2938 |
Pharosi | P08263, Tchem |
PROi | PR:P08263 |
RNActi | P08263, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000243955, Expressed in nephron tubule and 163 other tissues |
ExpressionAtlasi | P08263, baseline and differential |
Genevisiblei | P08263, HS |
Family and domain databases
DisProti | DP01506 |
Gene3Di | 3.40.30.10, 1 hit |
InterProi | View protein in InterPro IPR010987, Glutathione-S-Trfase_C-like IPR036282, Glutathione-S-Trfase_C_sf IPR040079, Glutathione_S-Trfase IPR004045, Glutathione_S-Trfase_N IPR003080, GST_alpha IPR004046, GST_C IPR036249, Thioredoxin-like_sf |
Pfami | View protein in Pfam PF00043, GST_C, 1 hit PF02798, GST_N, 1 hit |
PRINTSi | PR01266, GSTRNSFRASEA |
SFLDi | SFLDS00019, Glutathione_Transferase_(cytos, 1 hit |
SUPFAMi | SSF47616, SSF47616, 1 hit SSF52833, SSF52833, 1 hit |
PROSITEi | View protein in PROSITE PS50405, GST_CTER, 1 hit PS50404, GST_NTER, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GSTA1_HUMAN | |
Accessioni | P08263Primary (citable) accession number: P08263 Secondary accession number(s): Q14750, Q5GHF8, Q5SZC1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1988 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 215 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations