Glutathione S-transferase Mu 1 (GSTM1)

The protein contains 218 amino acids for an estimated molecular weight of 25712 Da.

 

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). (updated: June 17, 2020)

Protein identification was indicated in the following studies:

  1. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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VariantDescription
allele GSTM1B
dbSNP:rs449856

The reference OMIM entry for this protein is 138350

Glutathione s-transferase, mu-1; gstm1
Glutathione s-transferase m1
Glutathione transferase, class mu, 1
Gst1
Liver and fibroblast gst1

DESCRIPTION

The glutathione S-transferases (GST; EC 2.5.1.18) are a family of enzymes responsible for the metabolism of a broad range of xenobiotics and carcinogens (Mannervik, 1985). This enzyme catalyzes the reaction of glutathione with a wide variety of organic compounds to form thioethers, a reaction that is sometimes a first step in a detoxification process leading to mercapturic acid formation. Based on amino acid sequence similarities and antibody cross-reactivities, the mammalian cytosolic GSTs are divided into several classes, including alpha (e.g., 138359), mu, kappa (602321), theta (e.g., 600436), pi (134660), omega (605482), and zeta (603758). In addition, there is a class of microsomal GSTs (e.g., 138330). Each class is encoded by a single gene or a gene family.

CLONING

Board (1981) showed that the most active GSTs of liver are the products of 2 autosomal loci, GST1 (GSTM1) and GST2 (GSTA2; 138360), both of which are polymorphic. Strange et al. (1984) reported that GST1 is easily demonstrable in adult liver, kidney, adrenal and stomach but is only weakly expressed in skeletal and cardiac muscle and not at all in fetal liver, fibroblasts, erythrocytes, lymphocytes and platelets. GST2 is not detectable in the last 4 tissues but is found in many other tissues including fetal liver. GST3 (GSTP1; 134660) is found in every tissue except adult liver. DeJong et al. (1988) isolated a cDNA clone that encodes a human liver GST H(b) subunit representing GST1.

MAPPING

By in situ hybridization, DeJong et al. (1988) mapped the GST1 gene to chromosome 1p31. Zhong et al. (1992) used oligonucleotide primers specific for intron 5 sequences in the GSTM1 gene to amplify a unique 718-bp fragment. They confirmed the assignment to 1p by analysis of DNA from a panel of somatic cell hybrids and refined the localization to 1p13 by linkage analysis in 3-generation CEPH families. Pearson et al. (1993) used locus-specific PCR primer pairs spanning exon 6, intron 6, and exon 7 as probes on DNA from human/hamster somatic cell hybrids to map 5 glutathione transferase genes to chromosome 1: GSTM1, GSTM2 (138380), GSTM3 (138390), GSTM4 (138333), and GSTM5 (138385). For GSTM1, the assignment was confirmed by Southern blot hybridization. The organization of the 5 genes was confirmed by the isolation of a YAC clone that contained all 5. With this clone, the location of this cluster on chromosome 1 was confirmed by fluorescence in situ hybridization and regionalized to a point in or near 1p13.3. Xu et al. (1998) reported that 4 mu GST genes are tightly clustered. These genes are spaced approximately 20 kb apart and are arranged in the following order: 5-prime--GSTM4--GSTM2--GSTM1--GSTM5--3-prime. Islam et al. (1989) mapped a GST mu gene to human chromosome 3 (138385).

NOMENCLATURE

Mannervik et al. (1992) gave recommendations on nomenclature for human glutathione transferases.

MOLECULAR GENETICS

Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988). A null allele at the GSTM1 locus has a high frequency of about 0.7 (Board et al., 1990). The GST1 null phenotype has a frequency of greater than 50% among Caucasian, Chinese, and Indian populations (Board, 1981; Board et al., 1990). The GSTM1 null phenotype appears to be caused by the deletion of the GSTM1 gene (Seidegard et al., 1988, 1990). The close physical proximity of the GSTM1 and GSTM2 loci, which share 99% nucleotide s ... More on the omim web site

Subscribe to this protein entry history

June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 138350 was added.