MGMT_YEAST
ID MGMT_YEAST Reviewed; 188 AA.
AC P26188; D6VRF4;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Methylated-DNA--protein-cysteine methyltransferase;
DE EC=2.1.1.63 {ECO:0000269|PubMed:1993655, ECO:0000269|PubMed:2065659};
DE AltName: Full=6-O-methylguanine-DNA methyltransferase;
DE Short=MGMT;
DE AltName: Full=DNA repair MTase;
DE AltName: Full=O-6-methylguanine-DNA-alkyltransferase;
GN Name=MGT1; OrderedLocusNames=YDL200C; ORFNames=D1204;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=2065659; DOI=10.1002/j.1460-2075.1991.tb07753.x;
RA Xiao W., Derfler B., Chen J., Samson L.;
RT "Primary sequence and biological functions of a Saccharomyces cerevisiae
RT O6-methylguanine/O4-methylthymine DNA repair methyltransferase gene.";
RL EMBO J. 10:2179-2186(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION.
RC STRAIN=ATCC 44774 / DBY747;
RX PubMed=1641326; DOI=10.1093/nar/20.14.3599;
RA Xiao W., Samson L.;
RT "The Saccharomyces cerevisiae MGT1 DNA repair methyltransferase gene: its
RT promoter and entire coding sequence, regulation and in vivo biological
RT functions.";
RL Nucleic Acids Res. 20:3599-3606(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=9046097;
RX DOI=10.1002/(sici)1097-0061(199702)13:2<163::aid-yea54>3.0.co;2-4;
RA Bahr A., Moeller-Rieker S., Hankeln T., Kraemer C., Protin U.,
RA Schmidt E.R.;
RT "The nucleotide sequence of a 39 kb segment of yeast chromosome IV: 12 new
RT open reading frames, nine known genes and one gene for Gly-tRNA.";
RL Yeast 13:163-169(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-135.
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8896272;
RX DOI=10.1002/(sici)1097-0061(199609)12:10b<1065::aid-yea995>3.0.co;2-f;
RA Verhasselt P., Voet M., Mathys J., Volckaert G.;
RT "The sequence of 23 kb surrounding the SNF3 locus on the left arm of yeast
RT chromosome IV reveals the location of five known genes and characterizes at
RT least six new open reading frames including putative genes for ribosomal
RT protein L35 and a sugar transport protein.";
RL Yeast 12:1065-1070(1996).
RN [7]
RP FUNCTION, CHARACTERIZATION, AND LEVEL OF PROTEIN EXPRESSION.
RX PubMed=2403555; DOI=10.1016/s0021-9258(19)40188-9;
RA Sassanfar M., Samson L.;
RT "Identification and preliminary characterization of an O6-methylguanine DNA
RT repair methyltransferase in the yeast Saccharomyces cerevisiae.";
RL J. Biol. Chem. 265:20-25(1990).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1993655; DOI=10.1016/s0021-9258(18)49912-7;
RA Sassanfar M., Dosanjh M.K., Essigmann J.M., Samson L.;
RT "Relative efficiencies of the bacterial, yeast, and human DNA
RT methyltransferases for the repair of O6-methylguanine and O4-
RT methylthymine.";
RL J. Biol. Chem. 266:2767-2771(1991).
RN [9]
RP INDUCTION.
RX PubMed=7549791;
RA Joo J.H., Rho J.K., Kim J.H., Kim W.J., Choe S.Y., Park S.D.;
RT "Expression of yeast O6-methylguanine-DNA methyltransferase (MGMT) gene.";
RL Cell. Mol. Biol. 41:545-553(1995).
RN [10]
RP IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=12748633; DOI=10.1038/nature01644;
RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.;
RT "Sequencing and comparison of yeast species to identify genes and
RT regulatory elements.";
RL Nature 423:241-254(2003).
RN [11]
RP IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=12775844; DOI=10.1126/science.1084337;
RA Cliften P.F., Sudarsanam P., Desikan A., Fulton L., Fulton B., Majors J.,
RA Waterston R., Cohen B.A., Johnston M.;
RT "Finding functional features in Saccharomyces genomes by phylogenetic
RT footprinting.";
RL Science 301:71-76(2003).
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. Prefers
CC double-stranded DNA over single-stranded DNA as substrate.
CC {ECO:0000269|PubMed:1993655, ECO:0000269|PubMed:2065659,
CC ECO:0000269|PubMed:2403555}.
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 ECO:0000269|PubMed:1993655, ECO:0000269|PubMed:2065659};
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 ECO:0000269|PubMed:1993655, ECO:0000269|PubMed:2065659};
CC -!- INTERACTION:
CC P26188; P39009: DUN1; NbExp=2; IntAct=EBI-10873, EBI-6194;
CC P26188; P19812: UBR1; NbExp=2; IntAct=EBI-10873, EBI-19909;
CC P26188; P33202: UFD4; NbExp=2; IntAct=EBI-10873, EBI-20010;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- INDUCTION: In contrast to some bacterial and mammalian enzymes, MGT1 is
CC not induced by alkylating agents. {ECO:0000269|PubMed:7549791}.
CC -!- MISCELLANEOUS: Present with 150 molecules/cell in log phase YPD medium,
CC but not detectable in stationary phase cells.
CC {ECO:0000269|PubMed:2403555}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA34780.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA42920.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA67469.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA98777.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA98778.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X60368; CAA42920.1; ALT_INIT; Genomic_DNA.
DR EMBL; M94227; AAA34780.1; ALT_INIT; Genomic_DNA.
DR EMBL; X99000; CAA67469.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z74248; CAA98778.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z74247; CAA98777.1; ALT_INIT; Genomic_DNA.
DR EMBL; X83276; CAA58247.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11664.1; -; Genomic_DNA.
DR PIR; S29370; XUBYMC.
DR RefSeq; NP_010081.2; NM_001180260.1.
DR AlphaFoldDB; P26188; -.
DR SMR; P26188; -.
DR BioGRID; 31846; 168.
DR DIP; DIP-7461N; -.
DR IntAct; P26188; 50.
DR STRING; 4932.YDL200C; -.
DR PaxDb; P26188; -.
DR PRIDE; P26188; -.
DR EnsemblFungi; YDL200C_mRNA; YDL200C; YDL200C.
DR GeneID; 851327; -.
DR KEGG; sce:YDL200C; -.
DR SGD; S000002359; MGT1.
DR VEuPathDB; FungiDB:YDL200C; -.
DR eggNOG; KOG4062; Eukaryota.
DR GeneTree; ENSGT00390000015799; -.
DR HOGENOM; CLU_000445_52_2_1; -.
DR InParanoid; P26188; -.
DR OMA; TFIETEV; -.
DR BioCyc; YEAST:G3O-29584-MON; -.
DR PRO; PR:P26188; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P26188; protein.
DR GO; GO:0005634; C:nucleus; IC:SGD.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003908; F:methylated-DNA-[protein]-cysteine S-methyltransferase activity; IDA:SGD.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IMP:SGD.
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; 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 TIGRFAMs; TIGR00589; ogt; 1.
DR PROSITE; PS00374; MGMT; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA repair; DNA-binding; Methyltransferase; Nucleus;
KW Reference proteome; Transferase.
FT CHAIN 1..188
FT /note="Methylated-DNA--protein-cysteine methyltransferase"
FT /id="PRO_0000139362"
FT ACT_SITE 151
FT /note="Nucleophile; methyl group acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10017"
FT BINDING 120
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 121
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 157
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
SQ SEQUENCE 188 AA; 21499 MW; 956E71B47016E47D CRC64;
MKELLYYTFI ETEVTGAFLV FREKTQNLVF ASLGNDKLFL LGKVEGFLKK HEKQDTMYDL
QELKEAETYK KSIENYTICL ENKMPLPSGA IPFEFLFGTD FQRKVWNELL NVEHGHVVTY
GDIAKRIGKP TAARSVGRAC GSNNLALLVP CHRIVGSNRK LTGYKWSCKL KEQLLNNEKE
NSLSLSRL
