MGMT_CRIGR
ID MGMT_CRIGR Reviewed; 209 AA.
AC P26186;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Methylated-DNA--protein-cysteine methyltransferase;
DE EC=2.1.1.63;
DE AltName: Full=6-O-methylguanine-DNA methyltransferase;
DE Short=MGMT;
DE AltName: Full=O-6-methylguanine-DNA-alkyltransferase;
GN Name=MGMT;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=1579490; DOI=10.1093/nar/20.8.1891;
RA Rafferty J.A., Elder R.H., Watson A.J., Cawkwell L., Potter P.M.,
RA Margison G.P.;
RT "Isolation and partial characterisation of a Chinese hamster O6-
RT alkylguanine-DNA alkyltransferase cDNA.";
RL Nucleic Acids Res. 20:1891-1895(1992).
CC -!- FUNCTION: Involved in the cellular defense against the biological
CC effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in
CC DNA. Repairs the methylated nucleobase in DNA by stoichiometrically
CC transferring the methyl group to a cysteine residue in the enzyme. This
CC is a suicide reaction: the enzyme is irreversibly inactivated.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 6-O-methyl-2'-deoxyguanosine in DNA + L-cysteinyl-[protein]
CC = a 2'-deoxyguanosine in DNA + S-methyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:24000, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132,
CC Rhea:RHEA-COMP:11367, Rhea:RHEA-COMP:11368, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:82612, ChEBI:CHEBI:85445, ChEBI:CHEBI:85448; EC=2.1.1.63;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10017};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-O-methyl-thymidine in DNA + L-cysteinyl-[protein] = a
CC thymidine in DNA + S-methyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:53428, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132,
CC Rhea:RHEA-COMP:13555, Rhea:RHEA-COMP:13556, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:82612, ChEBI:CHEBI:137386, ChEBI:CHEBI:137387;
CC EC=2.1.1.63; Evidence={ECO:0000255|PROSITE-ProRule:PRU10017};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- MISCELLANEOUS: This enzyme catalyzes only one turnover and therefore is
CC not strictly catalytic. According to one definition, an enzyme is a
CC biocatalyst that acts repeatedly and over many reaction cycles.
CC -!- SIMILARITY: Belongs to the MGMT family. {ECO:0000305}.
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DR EMBL; X65081; CAA46209.1; -; mRNA.
DR AlphaFoldDB; P26186; -.
DR SMR; P26186; -.
DR STRING; 10029.XP_007608309.1; -.
DR eggNOG; KOG4062; Eukaryota.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003908; F:methylated-DNA-[protein]-cysteine S-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0006304; P:DNA modification; IEA:UniProt.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd06445; ATase; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001497; MethylDNA_cys_MeTrfase_AS.
DR InterPro; IPR014048; MethylDNA_cys_MeTrfase_DNA-bd.
DR InterPro; IPR036217; MethylDNA_cys_MeTrfase_DNAb.
DR InterPro; IPR008332; MethylG_MeTrfase_N.
DR InterPro; IPR036631; MGMT_N_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF01035; DNA_binding_1; 1.
DR Pfam; PF02870; Methyltransf_1N; 1.
DR SUPFAM; SSF46767; SSF46767; 1.
DR SUPFAM; SSF53155; SSF53155; 1.
DR TIGRFAMs; TIGR00589; ogt; 1.
DR PROSITE; PS00374; MGMT; 1.
PE 2: Evidence at transcript level;
KW DNA damage; DNA repair; DNA-binding; Metal-binding; Methyltransferase;
KW Nucleus; Phosphoprotein; Transferase; Zinc.
FT CHAIN 1..209
FT /note="Methylated-DNA--protein-cysteine methyltransferase"
FT /id="PRO_0000139358"
FT REGION 35..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Nucleophile; methyl group acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10017"
FT BINDING 5
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 29
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 99
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 118
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 119
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16455"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16455"
SQ SEQUENCE 209 AA; 22333 MW; 38CD50618BAB8A8D CRC64;
MAETCKMKYT VFHSPLGKIE LCGCERGLHG IRFLSGKTPS SDPKEAPASP ELLGGPEDLP
ESLVQCTTWL EAYFQEPAAT EGLPLPALHH PVFQQDSFTR QVLWKLLKVV KFGEMVSYQQ
LAALAGNPKA ARAVGGAMRN NPVPILIPCH RVICSNGSIG NYSGGGQAVK EWLLAHEGIP
TRQPACKDLG LTGTRLKPSG GSTSSKLSG
