Microsomal glutathione S-transferase 2 (MGST2)

The protein contains 147 amino acids for an estimated molecular weight of 16621 Da.

 

Catalyzes several different glutathione-dependent reactions (PubMed:8703034, PubMed:9278457, PubMed:23409838, PubMed:26656251, PubMed:26066610). Catalyzes the glutathione-dependent reduction of lipid hydroperoxides, such as 5-HPETE (PubMed:9278457, PubMed:23409838). Has glutathione transferase activity, toward xenobiotic electrophiles, such as 1-chloro-2, 4-dinitrobenzene (CDNB) (PubMed:23409838, PubMed:8703034). Catalyzes also the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4 (LTC4) (PubMed:23409838, PubMed:26656251). Involved in oxidative DNA damage induced by ER stress and anticancer agents by activating LTC4 biosynthetic machinery in nonimmune cells (PubMed:26656251). (updated: June 17, 2020)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. 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.

This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 35

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VariantDescription
dbSNP:rs8192111

No binding partner found

The reference OMIM entry for this protein is 601733

Glutathione s-transferase, microsomal, 2; mgst2
Gst2

DESCRIPTION

Glutathione S-transferases (GSTs), such as MGST2, are products of a gene superfamily that catalyze the conjugation of glutathione with a variety of xenobiotics and their reactive metabolites (Jakobsson et al., 1996).

CLONING

Two proteins involved in leukotriene biosynthesis are 5-lipoxygenase-activating protein (FLAP; 603700) and leukotriene (LT) C4 synthase (LTC4S; 246530); these proteins are 31% identical at the amino acid level. Jakobsson et al. (1996) identified a novel human gene in the FLAP/LTC4 synthase gene family which they termed microsomal glutathione S-transferase II (microsomal GST-II). This gene encodes a 147-amino acid polypeptide which is 44% identical to LTC4 synthase, 33% identical to FLAP, and 11% identical to human microsomal GST1 (138330). Northern blot analysis found that the gene is expressed as a 0.6-kb transcript in a variety of human tissues, but only weakly expressed (if at all) in lung, brain, placenta, and bone marrow. In contrast, FLAP mRNA is expressed in lung, various organs of the immune system, and peripheral blood leukocytes. Sjostrom et al. (2001) found that MGST2 was the only GST expressed in human umbilical vein endothelial cells (HUVECs). Northern blot analysis of HUVECs detected major and minor mRNAs at about 0.7 and 0.6 kb, respectively. Western blot analysis of HUVEC lysate detected MGST2 at an apparent molecular mass of about 16 kD.

GENE FUNCTION

Jakobsson et al. (1996) showed that the enzyme encoded by the GST2 gene is associated with cell microsomes and can catalyze the production of LTC4 from LTA4 and reduced glutathione. Sjostrom et al. (2001) found that MGST2 accepted both the free acid and the methyl ester of LTA4 as substrate, but the free acid was the preferred substrate. MGST2 was susceptible to dose-dependent inhibition by its product, LTC4. The gamma-glutamyl-cysteinyl-glycyl moiety of LTC4 was important for inhibition of MGST2, presumably via interaction with a GSH-binding pocket.

MAPPING

Jakobsson et al. (1996) localized the MGST2 gene to human chromosome 4q28-q31 by fluorescence in situ hybridization. ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 601733 was added.

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

Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

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