P09488 (GSTM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutathione S-transferase Mu 1
EC=2.5.1.18

Alternative name(s):
GST HB subunit 4
GST class-mu 1
GSTM1-1
GSTM1a-1a
GSTM1b-1b
GTH4

Gene names

Name:	GSTM1
Synonyms:	GST1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	218 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Ref.18
Catalytic activity	RX + glutathione = HX + R-S-glutathione. Ref.18
Subunit structure	Homodimer.
Subcellular location	Cytoplasm.
Tissue specificity	Liver (at protein level). Ref.8
Polymorphism	There are two alleles; GSTM1A and GSTM1B which differ in position 173.
Sequence similarities	Belongs to the GST superfamily. Mu family. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular detoxification of nitrogen compound Inferred from direct assay PubMed 8373352. Source: BHF-UCL glutathione metabolic process Inferred from direct assay PubMed 8373352. Source: BHF-UCL nitrobenzene metabolic process Inferred from direct assay PubMed 8373352. Source: BHF-UCL xenobiotic catabolic process Inferred from direct assay PubMed 8373352. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	glutathione binding Inferred from direct assay PubMed 8373352. Source: BHF-UCL glutathione transferase activity Inferred from direct assay PubMed 8373352. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P09488-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P09488-2)

The sequence of this isoform differs from the canonical sequence as follows:
     153-189: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Chain

2 – 218

217

Glutathione S-transferase Mu 1

PRO_0000185816

Regions

Domain

2 – 88

87

GST N-terminal

Domain

90 – 208

119

GST C-terminal

Region

7 – 8

2

Glutathione binding

Region

46 – 50

5

Glutathione binding

Region

59 – 60

2

Glutathione binding

Region

72 – 73

2

Glutathione binding

Sites

Binding site

116

1

Substrate

Amino acid modifications

Modified residue

23

1

Phosphotyrosine By similarity

Modified residue

33

1

Phosphotyrosine By similarity

Modified residue

34

1

Phosphothreonine By similarity

Natural variations

Alternative sequence

153 – 189

37

Missing in isoform 2.

VSP_036618

Natural variant

173

1

K → N in allele GSTM1B. Ref.3 Ref.5
Corresponds to variant rs1065411 [ dbSNP | Ensembl ].

VAR_003617

Natural variant

210

1

S → T.
Corresponds to variant rs449856 [ dbSNP | Ensembl ].

VAR_014497

Experimental info

Mutagenesis

7

1

Y → F: Reduces catalytic activity 100-fold. Ref.18

Mutagenesis

108

1

H → Q: Reduces catalytic activity by half. Ref.17 Ref.18

Mutagenesis

108

1

H → S: Changes the properties of the enzyme toward some substrates. Ref.17 Ref.18

Mutagenesis

109

1

M → I: Reduces catalytic activity by half. Ref.18

Mutagenesis

116

1

Y → A: Reduces catalytic activity 10-fold. Ref.18

Mutagenesis

116

1

Y → F: Slight increase of catalytic activity. Ref.18

Sequence conflict

44

1

S → T in CAA48636. Ref.7

Sequence conflict

207

1

P → T in AAT06767. Ref.4

Secondary structure

1

.

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218

Helix Strand Turn

Details...

Beta strand

3 – 11

9

Helix

12 – 14

3

Helix

15 – 23

9

Beta strand

28 – 33

6

Turn

38 – 41

4

Helix

44 – 50

7

Beta strand

60 – 65

6

Beta strand

68 – 72

5

Helix

73 – 83

11

Helix

91 – 115

25

Helix

120 – 142

23

Beta strand

146 – 152

7

Helix

156 – 170

15

Turn

172 – 177

6

Helix

179 – 189

11

Helix

192 – 198

7

Beta strand

200 – 202

3

Beta strand

214 – 216

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 98FB03E87B83A31B	FASTA	218	25,712
	10 20 30 40 50 60 MPMILGYWDI RGLAHAIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL 70 80 90 100 110 120 PYLIDGAHKI TQSNAILCYI ARKHNLCGET EEEKIRVDIL ENQTMDNHMQ LGMICYNPEF 130 140 150 160 170 180 EKLKPKYLEE LPEKLKLYSE FLGKRPWFAG NKITFVDFLV YDVLDLHRIF EPKCLDAFPN 190 200 210 LKDFISRFEG LEKISAYMKS SRFLPRPVFS KMAVWGNK
	Isoform 2 [UniParc]. Checksum: 1FB16A0418115A26	FASTA	181	21,253
	10 20 30 40 50 60 MPMILGYWDI RGLAHAIRLL LEYTDSSYEE KKYTMGDAPD YDRSQWLNEK FKLGLDFPNL 70 80 90 100 110 120 PYLIDGAHKI TQSNAILCYI ARKHNLCGET EEEKIRVDIL ENQTMDNHMQ LGMICYNPEF 130 140 150 160 170 180 EKLKPKYLEE LPEKLKLYSE FLGKRPWFAG NKGLEKISAY MKSSRFLPRP VFSKMAVWGN K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human liver glutathione S-transferase gene superfamily: expression and chromosome mapping of an Hb subunit cDNA." Dejong J.L., Chang C.M., Whang Peng J., Knutsen T., Tu C.-P.D. Nucleic Acids Res. 16:8541-8554(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Hereditary differences in the expression of the human glutathione transferase active on trans-stilbene oxide are due to a gene deletion." Seidegaard J., Vorachek W.R., Pero R.W., Pearson W.R. Proc. Natl. Acad. Sci. U.S.A. 85:7293-7297(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	Chen P., Wu Y., Zhang C., Han L., Wu Y., Xie D., Chen L. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ASN-173. Tissue: Liver.
[4]	Chen P., Zhang C., Xie D., Wu Y., Han L., Chen L. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Liver.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASN-173.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[7]	"Deduced amino acid sequence, gene structure and chromosomal location of a novel human class Mu glutathione S-transferase, GSTM4." Zhong S., Spurr N.K., Hayes J.D., Wolf C.R. Biochem. J. 291:41-50(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-189 (ISOFORM 1).
[8]	"Immunochemical evidence for the occurrence of Mu class glutathione S-transferase in human fetal livers." Mera N., Ohmori S., Itahashi K., Kiuchi M., Igarashi T., Rikihisa T., Kitada M. J. Biochem. 116:315-320(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-31, TISSUE SPECIFICITY. Tissue: Fetal liver.
[9]	"Purification and characterization of glutathione transferases with an activity toward nitroglycerin from human aorta and heart. Multiplicity of the human class Mu forms." Tsuchida S., Maki T., Sato K. J. Biol. Chem. 265:7150-7157(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-25. Tissue: Aorta and Heart.
[10]	"Structural evidence for three different types of glutathione transferase in human tissues." Alin P., Mannervik B., Joernvall H. FEBS Lett. 182:319-322(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-24.
[11]	"Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties." Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M.K., Warholm M., Joernvall H. Proc. Natl. Acad. Sci. U.S.A. 82:7202-7206(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-24.
[12]	"Purification and characterization of human muscle glutathione S-transferases: evidence that glutathione S-transferase zeta corresponds to a locus distinct from GST1, GST2, and GST3." Singhal S.S., Ahmad H., Sharma R., Gupta S., Haque A.K., Awasthi Y.C. Arch. Biochem. Biophys. 285:64-73(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-15.
[13]	"Gender related differences in the expression and characteristics of glutathione S-transferases of human colon." Singhal S.S., Saxena M., Awasthi S., Ahmad H., Sharma R., Awasthi Y.C. Biochim. Biophys. Acta 1171:19-26(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-13. Tissue: Colon.
[14]	"Human ERp29: isolation, primary structural characterisation and two-dimensional gel mapping." Hubbard M.J., McHugh N.J. Electrophoresis 21:3785-3796(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 53-60, MASS SPECTROMETRY. Tissue: Liver.
[15]	"GST1 gene deletion determined by polymerase chain reaction." Comstock K.E., Sanderson B.J.S., Claflin G., Henner W.D. Nucleic Acids Res. 18:3670-3670(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 60-118.
[16]	"Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13." Pearson W.R., Vorachek W.R., Xu S.J., Berger R., Hart I., Vannais D., Patterson D. Am. J. Hum. Genet. 53:220-233(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 125-186.
[17]	"Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a." Patskovsky Y.V., Patskovska L.N., Listowsky I. Biochemistry 38:1193-1202(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS), MUTAGENESIS OF HIS-108.
[18]	"Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a." Patskovsky Y., Patskovska L., Almo S.C., Listowsky I. Biochemistry 45:3852-3862(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH GLUTAHIONE ANALOGS, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF TYR-7; HIS-108; MET-109 AND TYR-116.
+	Additional computationally mapped references.

Web resources

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X08020 mRNA. Translation: CAA30821.1.
J03817 mRNA. Translation: AAA59203.1.
AY510272 mRNA. Translation: AAR85979.1.
AY532926 mRNA. Translation: AAT06767.1.
AY532927 mRNA. Translation: AAT06768.1.
CR541868 mRNA. Translation: CAG46666.1.
BC024005 mRNA. Translation: AAH24005.1.
X68676 Genomic DNA. Translation: CAA48636.1.
X51451 Genomic DNA. Translation: CAA35817.1.

IPI

IPI00152326.
IPI00218831.

PIR

S01719.

RefSeq

NP_000552.2. NM_000561.3.
NP_666533.1. NM_146421.2.

UniGene

Hs.301961.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GTU	X-ray	2.68	A/B/C/D	2-218	[»]
1XW6	X-ray	1.90	A/B/C/D	2-217	[»]
1XWK	X-ray	2.30	A/B/C	2-217	[»]
1YJ6	X-ray	2.50	A/B/C	2-217	[»]
2F3M	X-ray	2.70	A/B/C/D/E/F	1-217	[»]

ProteinModelPortal

P09488.

ModBase

Search...

Protein-protein interaction databases

IntAct

P09488. 6 interactions.

STRING

9606.ENSP00000311469.

PTM databases

PhosphoSite

P09488.

Polymorphism databases

DMDM

121735.

Proteomic databases

PaxDb

P09488.

PRIDE

P09488.

Protocols and materials databases

DNASU

2944.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309851; ENSP00000311469; ENSG00000134184.
ENST00000349334; ENSP00000234981; ENSG00000134184.

GeneID

2944.

KEGG

hsa:2944.

UCSC

uc001dyk.3. human.
uc001dyl.3. human.

Organism-specific databases

CTD

2944.

GeneCards

GC01P110231.

HGNC

HGNC:4632. GSTM1.

HPA

CAB022669.
CAB047357.

MIM

138350. gene.

neXtProt

NX_P09488.

PharmGKB

PA182.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG300089.

HOGENOM

HOG000115735.

HOVERGEN

HBG106842.

KO

K00799.

PhylomeDB

P09488.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P09488.

Gene expression databases

ArrayExpress

P09488.

Bgee

P09488.

CleanEx

HS_GSTM1.

Genevestigator

P09488.

GermOnline

ENSG00000134184. Homo sapiens.

Family and domain databases

Gene3D

1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR004046. GST_C.
IPR003081. GST_mu.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Pfam

PF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]

PRINTS

PR01267. GSTRNSFRASEM.

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P09488.

ChEMBL

CHEMBL2081.

ChiTaRS

GSTM1. human.

DrugBank

DB00143. Glutathione.

EvolutionaryTrace

P09488.

GenomeRNAi

2944.

NextBio

11663.

SOURCE

Search...

Entry information

Entry name

GSTM1_HUMAN

Accession

Primary (citable) accession number: P09488
Secondary accession number(s): Q5GHG0 , Q6FH88, Q8TC98, Q9UC96

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 151 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.