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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; P21266; HS. 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 //