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NameMethylated-DNA--protein-cysteine methyltransferase
Synonyms
  • 2.1.1.63
  • 6-O-methylguanine-DNA methyltransferase
  • MGMT
  • O-6-methylguanine-DNA-alkyltransferase
Gene NameMGMT
OrganismHuman
Amino acid sequence
>lcl|BSEQ0010800|Methylated-DNA--protein-cysteine methyltransferase
MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL
AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG
LGGSSGLAGAWLKGAGATSGSPPAGRN
Number of residues207
Molecular Weight21645.83
Theoretical pI8.23
GO Classification
Functions
  • methylated-DNA-[protein]-cysteine S-methyltransferase activity
  • damaged DNA binding
  • methyltransferase activity
  • calcium ion binding
  • DNA-methyltransferase activity
  • DNA binding
Processes
  • DNA dealkylation involved in DNA repair
  • response to drug
  • positive regulation of DNA repair
  • DNA repair
  • regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • DNA methylation
  • cellular response to oxidative stress
  • response to toxic substance
  • DNA ligation
  • response to ethanol
  • mammary gland epithelial cell differentiation
  • response to folic acid
  • negative regulation of cell death
  • cellular response to organic cyclic compound
  • cellular response to ionizing radiation
Components
  • nucleoplasm
  • membrane
  • nucleus
General FunctionMethyltransferase activity
Specific FunctionInvolved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID34559
UniProtKB IDP16455
UniProtKB Entry NameMGMT_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0002276|624 bp
ATGGACAAGGATTGTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGCTGGAG
CTGTCTGGTTGTGAGCAGGGTCTGCACGAAATAAAGCTCCTGGGCAAGGGGACGTCTGCA
GCTGATGCCGTGGAGGTCCCAGCCCCCGCTGCGGTTCTCGGAGGTCCGGAGCCCCTGATG
CAGTGCACAGCCTGGCTGAATGCCTATTTCCACCAGCCCGAGGCTATCGAAGAGTTCCCC
GTGCCGGCACTTCACCATCCCGTTTTCCAGCAAGAGTCGTTCACCAGACAGGTGTTATGG
AAGCTGCTGAAGGTTGTGAAATTCGGAGAAGTGATTTCTTACCAGCAATTAGCAGCCCTG
GCAGGCAACCCCAAAGCCGCGCGAGCAGTGGGAGGAGCAATGAGAGGCAATCCTGTCCCC
ATCCTCATCCCGTGCCACAGAGTGGTCTGCAGCAGCGGAGCCGTGGGCAACTACTCCGGA
GGACTGGCCGTGAAGGAATGGCTTCTGGCCCATGAAGGCCACCGGTTGGGGAAGCCAGGC
TTGGGAGGGAGCTCAGGTCTGGCAGGGGCCTGGCTCAAGGGAGCGGGAGCTACCTCGGGC
TCCCCGCCTGCTGGCCGAAACTGA
GenBank Gene IDX54228
GeneCard IDNot Available
GenAtlas IDMGMT
HGNC IDHGNC:7059
Chromosome LocationNot Available
Locus10q26
References
  1. Tano K, Shiota S, Collier J, Foote RS, Mitra S: Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine. Proc Natl Acad Sci U S A. 1990 Jan;87(2):686-90. 2405387
  2. Rydberg B, Spurr N, Karran P: cDNA cloning and chromosomal assignment of the human O6-methylguanine-DNA methyltransferase. cDNA expression in Escherichia coli and gene expression in human cells. J Biol Chem. 1990 Jun 5;265(16):9563-9. 2188979
  3. Koike G, Maki H, Takeya H, Hayakawa H, Sekiguchi M: Purification, structure, and biochemical properties of human O6-methylguanine-DNA methyltransferase. J Biol Chem. 1990 Sep 5;265(25):14754-62. 2394694
  4. Hayakawa H, Koike G, Sekiguchi M: Expression and cloning of complementary DNA for a human enzyme that repairs O6-methylguanine in DNA. J Mol Biol. 1990 Jun 20;213(4):739-47. 2359121
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  7. von Wronski MA, Shiota S, Tano K, Mitra S, Bigner DD, Brent TP: Structural and immunological comparison of indigenous human O6-methylguanine-DNA methyltransferase with that encoded by a cloned cDNA. J Biol Chem. 1991 Jan 15;266(2):1064-70. 1985934
  8. Liem LK, Lim A, Li BF: Specificities of human, rat and E. coli O6-methylguanine-DNA methyltransferases towards the repair of O6-methyl and O6-ethylguanine in DNA. Nucleic Acids Res. 1994 May 11;22(9):1613-9. 8202360
  9. Crone TM, Goodtzova K, Edara S, Pegg AE: Mutations in human O6-alkylguanine-DNA alkyltransferase imparting resistance to O6-benzylguanine. Cancer Res. 1994 Dec 1;54(23):6221-7. 7954470
  10. Kanugula S, Goodtzova K, Edara S, Pegg AE: Alteration of arginine-128 to alanine abolishes the ability of human O6-alkylguanine-DNA alkyltransferase to repair methylated DNA but has no effect on its reaction with O6-benzylguanine. Biochemistry. 1995 May 30;34(21):7113-9. 7766621
  11. Edara S, Goodtzova K, Pegg AE: The role of tyrosine-158 in O6-alkylguanine-DNA alkyltransferase activity. Carcinogenesis. 1995 Jul;16(7):1637-42. 7614699
  12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  13. Daniels DS, Mol CD, Arvai AS, Kanugula S, Pegg AE, Tainer JA: Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding. EMBO J. 2000 Apr 3;19(7):1719-30. 10747039
  14. Wibley JE, Pegg AE, Moody PC: Crystal structure of the human O(6)-alkylguanine-DNA alkyltransferase. Nucleic Acids Res. 2000 Jan 15;28(2):393-401. 10606635
  15. Duguid EM, Rice PA, He C: The structure of the human AGT protein bound to DNA and its implications for damage detection. J Mol Biol. 2005 Jul 22;350(4):657-66. 15964013