MGMT_RAT
ID MGMT_RAT Reviewed; 209 AA.
AC P24528;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 156.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2049083; DOI=10.1016/0006-291x(91)91830-6;
RA Rahden-Staron I., Laval F.;
RT "cDNA cloning of the rat O6-methylguanine-DNA-methyltransferase.";
RL Biochem. Biophys. Res. Commun. 177:597-602(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2013136; DOI=10.1093/carcin/12.4.727;
RA Potter P.M., Rafferty J.A., Cawkwell L., Wilkinson M.C., Cooper D.P.,
RA O'Connor P.J., Margison G.P.;
RT "Isolation and cDNA cloning of a rat O6-alkylguanine-DNA-alkyltransferase
RT gene, molecular analysis of expression in rat liver.";
RL Carcinogenesis 12:727-733(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8467487;
RA Potter P.M., Harris L.C., Remack J.S., Edwards C.C., Brent T.P.;
RT "Ribozyme-mediated modulation of human O6-methylguanine-DNA
RT methyltransferase expression.";
RL Cancer Res. 53:1731-1734(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1945835; DOI=10.1093/nar/19.20.5597;
RA Sakumi K., Shiraishi A., Hayakawa H., Sekiguchi M.;
RT "Cloning and expression of cDNA for rat O6-methylguanine-DNA
RT methyltransferase.";
RL Nucleic Acids Res. 19:5597-5601(1991).
RN [5]
RP CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=8202360; DOI=10.1093/nar/22.9.1613;
RA Liem L.-K., Lim A., Li B.F.L.;
RT "Specificities of human, rat and E. coli O6-methylguanine-DNA
RT methyltransferases towards the repair of O6-methyl and O6-ethylguanine in
RT DNA.";
RL Nucleic Acids Res. 22:1613-1619(1994).
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; S61804; AAB20187.1; -; mRNA.
DR EMBL; M76704; AAA42052.1; -; mRNA.
DR EMBL; X54862; CAA38648.1; -; mRNA.
DR PIR; JN0071; XURTMC.
DR RefSeq; NP_036993.1; NM_012861.1.
DR AlphaFoldDB; P24528; -.
DR SMR; P24528; -.
DR STRING; 10116.ENSRNOP00000021537; -.
DR iPTMnet; P24528; -.
DR PhosphoSitePlus; P24528; -.
DR PaxDb; P24528; -.
DR Ensembl; ENSRNOT00000119456; ENSRNOP00000079311; ENSRNOG00000016038.
DR GeneID; 25332; -.
DR KEGG; rno:25332; -.
DR CTD; 4255; -.
DR RGD; 3087; Mgmt.
DR eggNOG; KOG4062; Eukaryota.
DR GeneTree; ENSGT00390000015799; -.
DR HOGENOM; CLU_000445_52_2_1; -.
DR InParanoid; P24528; -.
DR OMA; SPEMQRC; -.
DR OrthoDB; 1573162at2759; -.
DR PhylomeDB; P24528; -.
DR TreeFam; TF314064; -.
DR PRO; PR:P24528; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016038; Expressed in pancreas and 18 other tissues.
DR Genevisible; P24528; RN.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003908; F:methylated-DNA-[protein]-cysteine S-methyltransferase activity; IDA:RGD.
DR GO; GO:0008168; F:methyltransferase activity; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEP:RGD.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; IEP:RGD.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IDA:RGD.
DR GO; GO:0006281; P:DNA repair; ISO:RGD.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IEP:RGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0060548; P:negative regulation of cell death; IDA:RGD.
DR GO; GO:0045739; P:positive regulation of DNA repair; IDA:RGD.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; ISO:RGD.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0051593; P:response to folic acid; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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 1: Evidence at protein level;
KW Direct protein sequencing; DNA damage; DNA repair; DNA-binding;
KW Metal-binding; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..209
FT /note="Methylated-DNA--protein-cysteine methyltransferase"
FT /id="PRO_0000139361"
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"
SQ SEQUENCE 209 AA; 22244 MW; 61F8F51C8937D4A7 CRC64;
MAEICKMKYT VLDSPLGKIE LSGCERGLHG IRFLSGKTPN TDPTEAPACP EVLGGPEGVP
EPLVQCTAWL EAYFHEPAAT EGLPLPALHH PVFQQDSFTR QVLWKLLKVV KFGEMVSYQQ
LAALAGNPKA ARAVGGAMRS NPVPILIPCH RVIRSDGAIG NYSGGGQTVK EWLLAHEGIP
TGQPASKGLG LIGSWLKPSF ESSSPKPSG
