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Identification
HMDB Protein ID HMDBP02029
Secondary Accession Numbers
  • 7487
Name Methylated-DNA--protein-cysteine methyltransferase
Synonyms
  1. 6-O-methylguanine-DNA methyltransferase
  2. MGMT
  3. O-6-methylguanine-DNA-alkyltransferase
Gene Name MGMT
Protein Type Unknown
Biological Properties
General Function Involved in methylated-DNA-[protein]-cysteine S-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
Pathways Not Available
Reactions Not Available
GO Classification
Function
methylated-dna-[protein]-cysteine s-methyltransferase activity
catalytic activity
transferase activity
s-methyltransferase activity
transferase activity, transferring one-carbon groups
methyltransferase activity
Process
metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
dna metabolic process
dna repair
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location Chromosome:1
Locus 10q26
SNPs MGMT
Gene Sequence
>624 bp
ATGGACAAGGATTGTGAAATGAAACGCACCACACTGGACAGCCCTTTGGGGAAGCTGGAG
CTGTCTGGTTGTGAGCAGGGTCTGCACGAAATAAAGCTCCTGGGCAAGGGGACGTCTGCA
GCTGATGCCGTGGAGGTCCCAGCCCCCGCTGCGGTTCTCGGAGGTCCGGAGCCCCTGATG
CAGTGCACAGCCTGGCTGAATGCCTATTTCCACCAGCCCGAGGCTATCGAAGAGTTCCCC
GTGCCGGCACTTCACCATCCCGTTTTCCAGCAAGAGTCGTTCACCAGACAGGTGTTATGG
AAGCTGCTGAAGGTTGTGAAATTCGGAGAAGTGATTTCTTACCAGCAATTAGCAGCCCTG
GCAGGCAACCCCAAAGCCGCGCGAGCAGTGGGAGGAGCAATGAGAGGCAATCCTGTCCCC
ATCCTCATCCCGTGCCACAGAGTGGTCTGCAGCAGCGGAGCCGTGGGCAACTACTCCGGA
GGACTGGCCGTGAAGGAATGGCTTCTGGCCCATGAAGGCCACCGGTTGGGGAAGCCAGGC
TTGGGAGGGAGCTCAGGTCTGGCAGGGGCCTGGCTCAAGGGAGCGGGAGCTACCTCGGGC
TCCCCGCCTGCTGGCCGAAACTGA
Protein Properties
Number of Residues 207
Molecular Weight 21645.8
Theoretical pI 8.23
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Methylated-DNA--protein-cysteine methyltransferase
MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAVEVPAPAAVLGGPEPLM
QCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKLLKVVKFGEVISYQQLAAL
AGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSGGLAVKEWLLAHEGHRLGKPG
LGGSSGLAGAWLKGAGATSGSPPAGRN
GenBank ID Protein 34559
UniProtKB/Swiss-Prot ID P16455
UniProtKB/Swiss-Prot Entry Name MGMT_HUMAN
PDB IDs
GenBank Gene ID X54228
GeneCard ID MGMT
GenAtlas ID MGMT
HGNC ID HGNC:7059
References
General References
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  2. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP: Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9. [PubMed:15302935 ]
  3. Imami K, Sugiyama N, Kyono Y, Tomita M, Ishihama Y: Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal Sci. 2008 Jan;24(1):161-6. [PubMed:18187866 ]
  4. 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. [PubMed:15164054 ]
  5. 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. [PubMed:2405387 ]
  6. 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. [PubMed:2188979 ]
  7. 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. [PubMed:2394694 ]
  8. 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. [PubMed:2359121 ]
  9. 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. [PubMed:1985934 ]
  10. 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. [PubMed:8202360 ]
  11. 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. [PubMed:7954470 ]
  12. 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. [PubMed:7766621 ]
  13. Edara S, Goodtzova K, Pegg AE: The role of tyrosine-158 in O6-alkylguanine-DNA alkyltransferase activity. Carcinogenesis. 1995 Jul;16(7):1637-42. [PubMed:7614699 ]
  14. 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. [PubMed:10747039 ]
  15. 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. [PubMed:10606635 ]
  16. 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. [PubMed:15964013 ]