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methylated-DNA-protein-cysteine methyltransferase; 6-O-methylguanine-DNA methyltransferase; MGMT; O-6-methylguanine-DNA-alkyltransferase (MGMT)
Function:
- DNA repair protein
- O6-MGMT removes carcinogen induced O6-methylguanine adducts from DNA which result in G -> A mutations if left unrepaired
- stoichiometrically transfers the methyl group at the O-6 position to a Cys in the enzyme; this is a suicide reaction: the enzyme is irreversibly inactivated (thus technically not an enzyme)
DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine
Cofactor: binds 1 Zn+2
Structure: belongs to the MGMT family
Compartment: nucleus
Pathology:
- promoter hypermethylation of the gene & epigenetic silencing is associated with colon, lung, lymphoid & other tumors
General
DNA-binding protein
O-methyl transferase
phosphoprotein
Properties
SIZE: entity length = 207 aa
MW = 22 kD
COMPARTMENT: cell nucleus
MOTIF: Zn+2-binding site
SITE: 5-5
Thr phosphorylation site {T10}
Thr phosphorylation site {T11}
Zn+2-binding site
SITE: 24-24
Zn+2-binding site
SITE: 29-29
Zn+2-binding site
SITE: 85-85
binding site
SITE: 95-95
FOR-BINDING-OF: DNA; via amide nitrogen
DNA-binding motif
SITE: 114-114
binding site
SITE: 115-115
FOR-BINDING-OF: DNA; via amide nitrogen
DNA-binding motif
SITE: 123-123
DNA-binding motif
SITE: 128-128
cysteine residue {C145}
binding site
SITE: 151-151
FOR-BINDING-OF: DNA; via amide nitrogen
Ser phosphorylation site {S201}
Database Correlations
OMIM 156569
UniProt P16455
PFAM correlations
ENZYME 2.1.1.63
References
- UniProt :accession P16455
- Jones PA, Baylin SB.
The fundamental role of epigenetic events in cancer.
Nat Rev Genet. 2002 Jun;3(6):415-28. Review.
PMID: 12042769