Methylated-DNA--protein-cysteine methyltransferase (MGMT)
The protein contains 207 amino acids for an estimated molecular weight of 21646 Da.
Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
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The reference OMIM entry for this protein is 156569
Methylguanine-dna methyltransferase; mgmt
CLONING
O(6)-alkylguanine is the major mutagenic and carcinogenic lesion in DNA induced by simple alkylating mutagens because of its preference for pairing with thymine during DNA replication. This adduct in DNA is removed by a ubiquitous and unique repair protein, O(6)-methylguanine-DNA methyltransferase (EC 2.1.1.63). This protein, unlike true enzymes, accepts the alkyl group from the lesion in a stoichiometric second-order reaction. The methyl-acceptor residue is cysteine. Tano et al. (1990) cloned the cDNA of the human MGMT gene in an expression vector on the basis of its rescue of a methyltransferase-deficient E. coli host.GENE STRUCTURE
Rydberg et al. (1990) concluded that the methyltransferase gene spans at least 15 kb.MAPPING
By study of DNA from mouse/human hybrid cell lines, Rydberg et al. (1990) mapped the MGMT gene to chromosome 10. Zunino et al. (1991) likewise mapped the MGMT gene to chromosome 10 by study of somatic cell hybrids. Using a panel of 5 human/rodent cell hybrids that divide chromosome 10 into 6 regions, Gardner et al. (1991) refined the localization of the gene to 10q24.33-qter. By nonradioactive in situ hybridization, Natarajan et al. (1992) mapped the MGMT gene to 10q26.GENE FUNCTION
Esteller et al. (2000) analyzed the MGMT promoter in tumor DNA by a methylation-specific PCR assay to determine whether methylation of the MGMT promoter is related to the responsiveness of gliomas (137800) to alkylating agents. The MGMT promoter was methylated in gliomas from 19 of 47 patients (40%). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status. The authors concluded that methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents. In an evaluation of combined radiotherapy and temozolomide for newly diagnosed glioblastoma, Hegi et al. (2004) found that methylation of the MGMT promoter in the tumor was associated with longer survival. Stupp et al. (2005) showed that the addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. Hegi et al. (2005) studied methylation of the MGMT promoter in newly diagnosed glioblastomas and found that patients with a methylated MGMT promoter in the glioblastoma benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit. Testicular germ cell tumors are classified into 2 major histologic subgroups, seminomas and nonseminomas. In a series of 70 testicular germ cell tumors, Smith-Sorensen et al. (2002) analyzed for methylation of CpG sites in the MGMT gene promoter and in exon 1-alpha of the cyclin-dependent kinase inhibitor 2A gene (CDKN2A; 600160). None of 55 tumors showed methylation of CDKN2A. On the other hand, high frequencies of MGMT promoter methylation and allelic imbalances at 10q markers were found in 32 of 69 (46%) and 50 of 70 (71%) tumors, respectively. A significantly higher methylation frequency was found in 24 of 35 nonseminomas (69%) compared to 8 of 33 seminomas (24%). Immunohistochemical analysis of the MGMT protein in a subgroup of the testicular tumors supported the hypothesis of gene silencing being the functional consequen ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 156569 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).