Methylated-DNA--protein-cysteine methyltransferase

Details

Name
Methylated-DNA--protein-cysteine methyltransferase
Synonyms
  • 2.1.1.63
  • 6-O-methylguanine-DNA methyltransferase
  • MGMT
  • O-6-methylguanine-DNA-alkyltransferase
Gene Name
MGMT
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010800|Methylated-DNA--protein-cysteine methyltransferase
MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL
AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG
LGGSSGLAGAWLKGAGATSGSPPAGRN
Number of residues
207
Molecular Weight
21645.83
Theoretical pI
8.23
GO Classification
Functions
calcium ion binding / damaged DNA binding / DNA binding / DNA-methyltransferase activity / methylated-DNA-[protein]-cysteine S-methyltransferase activity / methyltransferase activity
Processes
cellular response to ionizing radiation / cellular response to organic cyclic compound / cellular response to oxidative stress / DNA dealkylation involved in DNA repair / DNA ligation / DNA methylation / DNA repair / mammary gland epithelial cell differentiation / negative regulation of cell death / positive regulation of DNA repair / regulation of cysteine-type endopeptidase activity involved in apoptotic process / response to drug / response to ethanol / response to folic acid / response to toxic substance
Components
membrane / nucleoplasm / nucleus
General Function
Methyltransferase activity
Specific Function
Involved 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 Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0002276|624 bp
ATGGACAAGGATTGTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGCTGGAG
CTGTCTGGTTGTGAGCAGGGTCTGCACGAAATAAAGCTCCTGGGCAAGGGGACGTCTGCA
GCTGATGCCGTGGAGGTCCCAGCCCCCGCTGCGGTTCTCGGAGGTCCGGAGCCCCTGATG
CAGTGCACAGCCTGGCTGAATGCCTATTTCCACCAGCCCGAGGCTATCGAAGAGTTCCCC
GTGCCGGCACTTCACCATCCCGTTTTCCAGCAAGAGTCGTTCACCAGACAGGTGTTATGG
AAGCTGCTGAAGGTTGTGAAATTCGGAGAAGTGATTTCTTACCAGCAATTAGCAGCCCTG
GCAGGCAACCCCAAAGCCGCGCGAGCAGTGGGAGGAGCAATGAGAGGCAATCCTGTCCCC
ATCCTCATCCCGTGCCACAGAGTGGTCTGCAGCAGCGGAGCCGTGGGCAACTACTCCGGA
GGACTGGCCGTGAAGGAATGGCTTCTGGCCCATGAAGGCCACCGGTTGGGGAAGCCAGGC
TTGGGAGGGAGCTCAGGTCTGGCAGGGGCCTGGCTCAAGGGAGCGGGAGCTACCTCGGGC
TCCCCGCCTGCTGGCCGAAACTGA
Chromosome Location
Not Available
Locus
10q26
External Identifiers
ResourceLink
UniProtKB IDP16455
UniProtKB Entry NameMGMT_HUMAN
GenBank Protein ID34559
GenBank Gene IDX54228
GenAtlas IDMGMT
HGNC IDHGNC:7059
General 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02216S-MethylcysteineexperimentalunknownDetails
DB04531S-BenzylcysteineexperimentalunknownDetails
DB00151Cysteineapproved, nutraceuticalunknownDetails
DB01593Zincapproved, investigationalunknownDetails
DB11831DinitrochlorobenzeneinvestigationalunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownstabilizationDetails
DB14548Zinc sulfate, unspecified formapproved, experimentalunknownstabilizationDetails