ID GSTM3_HUMAN Reviewed; 225 AA.
AC P21266; O60550; Q96HA3;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 229.
DE RecName: Full=Glutathione S-transferase Mu 3;
DE EC=2.5.1.18;
DE AltName: Full=GST class-mu 3;
DE AltName: Full=GSTM3-3;
DE Short=hGSTM3-3;
GN Name=GSTM3; Synonyms=GST5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Brain, and Testis;
RX PubMed=2345169; DOI=10.1016/s0021-9258(19)38830-1;
RA Campbell E., Takahashi Y., Abramovitz M., Peretz M., Listowsky I.;
RT "A distinct human testis and brain mu-class glutathione S-transferase.
RT Molecular cloning and characterization of a form present even in
RT individuals lacking hepatic type mu isoenzymes.";
RL J. Biol. Chem. 265:9188-9193(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9882431; DOI=10.1006/abbi.1998.0964;
RA Patskovsky Y.V., Huang M.Q., Takayama T., Listowsky I., Pearson W.R.;
RT "Distinctive structure of the human GSTM3 gene-inverted orientation
RT relative to the mu class glutathione transferase gene cluster.";
RL Arch. Biochem. Biophys. 361:85-93(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-224.
RC TISSUE=Brain, and Uterus;
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 [5]
RP PROTEIN SEQUENCE OF N-TERMINUS.
RC TISSUE=Testis;
RX PubMed=8373352; DOI=10.1042/bj2940373;
RA Ross V.L., Board P.G.;
RT "Molecular cloning and heterologous expression of an alternatively spliced
RT human Mu class glutathione S-transferase transcript.";
RL Biochem. J. 294:373-380(1993).
RN [6]
RP PROTEIN SEQUENCE OF 190-209.
RX PubMed=8218382; DOI=10.1016/0167-4838(93)90047-u;
RA Hussey A.J., Hayes J.D.;
RT "Human Mu-class glutathione S-transferases present in liver, skeletal
RT muscle and testicular tissue.";
RL Biochim. Biophys. Acta 1203:131-141(1993).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-54 AND LYS-73, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), CATALYTIC ACTIVITY, FUNCTION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND MUTAGENESIS OF TYR-120 AND
RP ASN-213.
RX PubMed=10587441; DOI=10.1021/bi991714t;
RA Patskovsky Y.V., Patskovska L.N., Listowsky I.;
RT "An asparagine-phenylalanine substitution accounts for catalytic
RT differences between hGSTM3-3 and other human class mu glutathione S-
RT transferases.";
RL Biochemistry 38:16187-16194(1999).
CC -!- FUNCTION: Conjugation of reduced glutathione to a wide number of
CC exogenous and endogenous hydrophobic electrophiles. May govern uptake
CC and detoxification of both endogenous compounds and xenobiotics at the
CC testis and brain blood barriers. {ECO:0000269|PubMed:10587441}.
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:10587441};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.1 mM for 1-chloro-2,4-dinitrobenzene
CC {ECO:0000269|PubMed:10587441};
CC KM=0.084 mM for glutathione {ECO:0000269|PubMed:10587441};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10587441}.
CC -!- INTERACTION:
CC P21266; Q5SYC1: CLVS2; NbExp=3; IntAct=EBI-350350, EBI-12357161;
CC P21266; P21266: GSTM3; NbExp=10; IntAct=EBI-350350, EBI-350350;
CC P21266; Q03013: GSTM4; NbExp=4; IntAct=EBI-350350, EBI-713363;
CC P21266; P46439: GSTM5; NbExp=12; IntAct=EBI-350350, EBI-4312072;
CC P21266; Q12836: ZP4; NbExp=2; IntAct=EBI-350350, EBI-11783805;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Testis and brain.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the GST superfamily. Mu family. {ECO:0000305}.
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DR EMBL; J05459; AAA60964.1; -; mRNA.
DR EMBL; AF043105; AAC17866.1; -; Genomic_DNA.
DR EMBL; BT019945; AAV38748.1; -; mRNA.
DR EMBL; BC000088; AAH00088.1; -; mRNA.
DR EMBL; BC008790; AAH08790.1; -; mRNA.
DR CCDS; CCDS812.1; -.
DR PIR; A35295; A35295.
DR RefSeq; NP_000840.2; NM_000849.4.
DR PDB; 3GTU; X-ray; 2.80 A; B/D=2-225.
DR PDBsum; 3GTU; -.
DR AlphaFoldDB; P21266; -.
DR SMR; P21266; -.
DR BioGRID; 109202; 156.
DR IntAct; P21266; 25.
DR MINT; P21266; -.
DR STRING; 9606.ENSP00000354357; -.
DR ChEMBL; CHEMBL2242; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00291; Chlorambucil.
DR DrugBank; DB14002; D-alpha-Tocopherol acetate.
DR DrugBank; DB03619; Deoxycholic acid.
DR DrugBank; DB00143; Glutathione.
DR DrugBank; DB03310; Glutathione disulfide.
DR DrugBank; DB00163; Vitamin E.
DR MoonProt; P21266; -.
DR GlyGen; P21266; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P21266; -.
DR MetOSite; P21266; -.
DR PhosphoSitePlus; P21266; -.
DR SwissPalm; P21266; -.
DR BioMuta; GSTM3; -.
DR DMDM; 21264423; -.
DR OGP; P21266; -.
DR REPRODUCTION-2DPAGE; IPI00246975; -.
DR EPD; P21266; -.
DR jPOST; P21266; -.
DR MassIVE; P21266; -.
DR PaxDb; 9606-ENSP00000256594; -.
DR PeptideAtlas; P21266; -.
DR ProteomicsDB; 53855; -.
DR Pumba; P21266; -.
DR Antibodypedia; 33773; 250 antibodies from 32 providers.
DR CPTC; P21266; 3 antibodies.
DR DNASU; 2947; -.
DR Ensembl; ENST00000256594.7; ENSP00000256594.3; ENSG00000134202.12.
DR Ensembl; ENST00000361066.7; ENSP00000354357.2; ENSG00000134202.12.
DR GeneID; 2947; -.
DR KEGG; hsa:2947; -.
DR MANE-Select; ENST00000361066.7; ENSP00000354357.2; NM_000849.5; NP_000840.2.
DR AGR; HGNC:4635; -.
DR CTD; 2947; -.
DR DisGeNET; 2947; -.
DR GeneCards; GSTM3; -.
DR HGNC; HGNC:4635; GSTM3.
DR HPA; ENSG00000134202; Tissue enhanced (choroid).
DR MalaCards; GSTM3; -.
DR MIM; 138390; gene.
DR neXtProt; NX_P21266; -.
DR OpenTargets; ENSG00000134202; -.
DR Orphanet; 586; Cystic fibrosis.
DR PharmGKB; PA29024; -.
DR VEuPathDB; HostDB:ENSG00000134202; -.
DR eggNOG; KOG1695; Eukaryota.
DR GeneTree; ENSGT00940000157663; -.
DR HOGENOM; CLU_039475_2_0_1; -.
DR InParanoid; P21266; -.
DR OMA; KWANKRA; -.
DR OrthoDB; 5488107at2759; -.
DR PhylomeDB; P21266; -.
DR TreeFam; TF353040; -.
DR BRENDA; 2.5.1.18; 2681.
DR PathwayCommons; P21266; -.
DR Reactome; R-HSA-156590; Glutathione conjugation.
DR SABIO-RK; P21266; -.
DR SignaLink; P21266; -.
DR BioGRID-ORCS; 2947; 6 hits in 1155 CRISPR screens.
DR EvolutionaryTrace; P21266; -.
DR GeneWiki; GSTM3; -.
DR GenomeRNAi; 2947; -.
DR Pharos; P21266; Tbio.
DR PRO; PR:P21266; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P21266; Protein.
DR Bgee; ENSG00000134202; Expressed in right testis and 209 other cell types or tissues.
DR ExpressionAtlas; P21266; baseline and differential.
DR Genevisible; P21266; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0035686; C:sperm fibrous sheath; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0043295; F:glutathione binding; IDA:BHF-UCL.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
DR GO; GO:0070458; P:cellular detoxification of nitrogen compound; IDA:BHF-UCL.
DR GO; GO:0008065; P:establishment of blood-nerve barrier; TAS:ProtInc.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB.
DR GO; GO:0018916; P:nitrobenzene metabolic process; IDA:BHF-UCL.
DR GO; GO:0043627; P:response to estrogen; IEP:UniProtKB.
DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:BHF-UCL.
DR CDD; cd03209; GST_C_Mu; 1.
DR CDD; cd03075; GST_N_Mu; 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; IPR003081; GST_mu.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR11571; GLUTATHIONE S-TRANSFERASE; 1.
DR PANTHER; PTHR11571:SF133; GLUTATHIONE S-TRANSFERASE MU 3; 1.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF02798; GST_N; 1.
DR PRINTS; PR01267; GSTRNSFRASEM.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Isopeptide bond;
KW Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..225
FT /note="Glutathione S-transferase Mu 3"
FT /id="PRO_0000185822"
FT DOMAIN 5..92
FT /note="GST N-terminal"
FT DOMAIN 94..212
FT /note="GST C-terminal"
FT BINDING 11..12
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P08515"
FT BINDING 50..54
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P08515"
FT BINDING 63..64
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P08515"
FT BINDING 76..77
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P08515"
FT BINDING 120
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT CROSSLNK 54
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 73
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 224
FT /note="V -> I (in dbSNP:rs7483)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_014498"
FT MUTAGEN 120
FT /note="Y->A: No effect."
FT /evidence="ECO:0000269|PubMed:10587441"
FT MUTAGEN 120
FT /note="Y->F: Strongly increased catalytic activity."
FT /evidence="ECO:0000269|PubMed:10587441"
FT MUTAGEN 213
FT /note="N->F: Strongly increased catalytic activity."
FT /evidence="ECO:0000269|PubMed:10587441"
FT MUTAGEN 213
FT /note="N->G: No effect."
FT /evidence="ECO:0000269|PubMed:10587441"
FT CONFLICT 147
FT /note="G -> W (in Ref. 1; AAA60964)"
FT /evidence="ECO:0000305"
FT STRAND 7..15
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 19..27
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 77..87
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 95..120
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 124..146
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 159..174
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 183..193
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 196..203
FT /evidence="ECO:0007829|PDB:3GTU"
FT HELIX 205..208
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:3GTU"
FT STRAND 217..220
FT /evidence="ECO:0007829|PDB:3GTU"
SQ SEQUENCE 225 AA; 26560 MW; 79093161ECEF5396 CRC64;
MSCESSMVLG YWDIRGLAHA IRLLLEFTDT SYEEKRYTCG EAPDYDRSQW LDVKFKLDLD
FPNLPYLLDG KNKITQSNAI LRYIARKHNM CGETEEEKIR VDIIENQVMD FRTQLIRLCY
SSDHEKLKPQ YLEELPGQLK QFSMFLGKFS WFAGEKLTFV DFLTYDILDQ NRIFDPKCLD
EFPNLKAFMC RFEALEKIAA YLQSDQFCKM PINNKMAQWG NKPVC
//
