MGMT_MOUSE
ID MGMT_MOUSE Reviewed; 211 AA.
AC P26187; Q54A49;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 160.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1371399; DOI=10.1021/bi00122a001;
RA Shiota S., von Wronski M.A., Tano K., Bigner D.D., Brent T.P., Mitra S.;
RT "Characterization of cDNA encoding mouse DNA repair protein O6-
RT methylguanine-DNA methyltransferase and high-level expression of the wild-
RT type and mutant proteins in Escherichia coli.";
RL Biochemistry 31:1897-1903(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/HeJ, and C57BL/6J; TISSUE=Thymus;
RA Shimada Y., Kakinuma S., Kubo A., Nishimura M.;
RT "MGMT sequence of B6 and C3H mice.";
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; M84524; AAA37126.1; -; mRNA.
DR EMBL; AB092489; BAC16763.1; -; mRNA.
DR EMBL; AB092490; BAC16764.1; -; mRNA.
DR EMBL; BC031888; AAH31888.1; -; mRNA.
DR CCDS; CCDS21945.1; -.
DR PIR; A41809; A41809.
DR RefSeq; NP_032624.1; NM_008598.2.
DR RefSeq; XP_006507472.1; XM_006507409.3.
DR RefSeq; XP_006507473.1; XM_006507410.3.
DR AlphaFoldDB; P26187; -.
DR SMR; P26187; -.
DR BioGRID; 201415; 2.
DR STRING; 10090.ENSMUSP00000080224; -.
DR iPTMnet; P26187; -.
DR PhosphoSitePlus; P26187; -.
DR EPD; P26187; -.
DR MaxQB; P26187; -.
DR PaxDb; P26187; -.
DR PeptideAtlas; P26187; -.
DR PRIDE; P26187; -.
DR ProteomicsDB; 292236; -.
DR Antibodypedia; 32507; 898 antibodies from 42 providers.
DR DNASU; 17314; -.
DR Ensembl; ENSMUST00000081510; ENSMUSP00000080224; ENSMUSG00000054612.
DR GeneID; 17314; -.
DR KEGG; mmu:17314; -.
DR UCSC; uc009keq.1; mouse.
DR CTD; 4255; -.
DR MGI; MGI:96977; Mgmt.
DR VEuPathDB; HostDB:ENSMUSG00000054612; -.
DR eggNOG; KOG4062; Eukaryota.
DR GeneTree; ENSGT00390000015799; -.
DR HOGENOM; CLU_000445_52_2_1; -.
DR InParanoid; P26187; -.
DR OMA; SPEMQRC; -.
DR OrthoDB; 1573162at2759; -.
DR PhylomeDB; P26187; -.
DR TreeFam; TF314064; -.
DR BioGRID-ORCS; 17314; 5 hits in 112 CRISPR screens.
DR ChiTaRS; Mgmt; mouse.
DR PRO; PR:P26187; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P26187; protein.
DR Bgee; ENSMUSG00000054612; Expressed in proximal tubule and 64 other tissues.
DR Genevisible; P26187; MM.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003908; F:methylated-DNA-[protein]-cysteine S-methyltransferase activity; ISO:MGI.
DR GO; GO:0008168; F:methyltransferase activity; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IDA:MGI.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISO:MGI.
DR GO; GO:2000781; P:positive regulation of double-strand break repair; ISO:MGI.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
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..211
FT /note="Methylated-DNA--protein-cysteine methyltransferase"
FT /id="PRO_0000139360"
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 211 AA; 22435 MW; 838BB92B9A1083D6 CRC64;
MAETCKMKYS VLDSPLGKME LSGCERGLHG IRLLSGKTPN TDPTEAPATP EVLGGPEGVP
EPLVQCTAWL EAYFREPAAT EGLPLPALHH PVFQQDSFTR QVLWKLLKVV KFGETVSYQQ
LAALAGNPKA ARAVGGAMRS NPVPILIPCH RVVRSDGAIG HYSGGGQAVK EWLLAHEGIP
TGQPASKGLG LTGTWLKSSF ESTSSEPSGR N
