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Description:
Methylated-DNA--protein-cysteine methyltransferase (EC 2.1.1.63) (6-O-methylguanine-DNA methyltransferase) (MGMT) (O-6-methylguanine-DNA-alkyltransferase).
Molecular weight: 21646
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA ligation( GO:0006266 ) DNA repair( GO:0006281 )
Important dates:
01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
01-AUG-1990, sequence version 1.
07-MAR-2006, entry version 66.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein MGMT_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X54228 | CAA38137.1 | - |
| EMBL | M29971 | AAA59596.1 | - |
| EMBL | M31767 | AAA52317.1 | - |
| EMBL | M60761 | AAA59594.1 | - |
| EMBL | BT006714 | AAP35360.1 | - |
| EMBL | BC000824 | AAH00824.1 | - |
| PIR | A34889 | XUHUMC. | |
| PDB | 1EH6 | X-ray | A=1-207. |
| PDB | 1EH7 | X-ray | A=1-207. |
| PDB | 1EH8 | X-ray | A=1-207. |
| PDB | 1QNT | X-ray | A=1-176. |
| PDB | 1T38 | X-ray | A=1-176. |
| PDB | 1T39 | X-ray | A/B=1-176. |
| PDB | 1YFH | X-ray | A/B/C=1-179. |
| Ensembl | ENSG00000170430 | Homo sapiens.1 | |
| H-InvDB | HIX0009309 | -.1 | |
| HGNC | HGNC:7059 | MGMT.1 | |
| MIM | 156569 | gene. | |
| Reactome | P16455 | -.1 | |
| GO | GO:0005634 | C:nucleus | TAS. |
| GO | GO:0003677 | F:DNA binding | TAS. |
| GO | GO:0009008 | F:DNA-methyltransferase activity | TAS. |
| GO | GO:0006266 | P:DNA ligation | TAS. |
| InterPro | IPR008332 | MethylG_mtfrase. | |
| InterPro | IPR001497 | Methyltransf_1. | |
| InterPro | IPR011991 | Wing_hlx_DNA_bd. | |
| Pfam | PF01035 | DNA_binding_1 | 1. |
| Pfam | PF02870 | Methyltransf_1N | 1. |
| TIGRFAMs | TIGR00589 | ogt | 1. |
| PROSITE | PS00374 | MGMT | 1. |
Keywords:
3D-structure; Direct protein sequencing; DNA damage; DNA repair; Methyltransferase; Nuclear protein; Phosphorylation; Polymorphism; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-8.
RX MEDLINE=90138892; PubMed=2405387;
RA Tano K., Shiota S., Collier J., Foote R.S., Mitra S.;
RT "Isolation and structural characterization of a cDNA clone encoding
RT the human DNA repair protein for O6-alkylguanine.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:686-690(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=90264461; PubMed=2188979;
RA Rydberg B., Spurr N., Karran P.;
RT "cDNA cloning and chromosomal assignment of the human O6-
RT methylguanine-DNA methyltransferase. cDNA expression in Escherichia
RT coli and gene expression in human cells.";
RL J. Biol. Chem. 265:9563-9569(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=90368638; PubMed=2394694;
RA Koike G., Maki H., Takeya H., Hayakawa H., Sekiguchi M.;
RT "Purification, structure, and biochemical properties of human O6-
RT methylguanine-DNA methyltransferase.";
RL J. Biol. Chem. 265:14754-14762(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=90294292; PubMed=2359121;
RA Hayakawa H., Koike G., Sekiguchi M.;
RT "Expression and cloning of complementary DNA for a human enzyme that
RT repairs O6-methylguanine in DNA.";
RL J. Mol. Biol. 213:739-747(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [7]
RP PARTIAL PROTEIN SEQUENCE, AND ALKYL GROUP ACCEPTOR.
RX MEDLINE=91093213; PubMed=1985934;
RA von Wronski M.A., Shiota S., Tano K., Mitra S., Bigner D.D.,
RA Brent T.P.;
RT "Structural and immunological comparison of indigenous human O6-
RT methylguanine-DNA methyltransferase with that encoded by a cloned
RT cDNA.";
RL J. Biol. Chem. 266:1064-1070(1991).
RN [8]
RP CHARACTERIZATION.
RX MEDLINE=94261426; PubMed=8202360;
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
RT in DNA.";
RL Nucleic Acids Res. 22:1613-1619(1994).
RN [9]
RP PHOSPHORYLATION SITE SER-201.
RX PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
Feature:
CHAIN 1 207 Methylated-DNA--protein-cysteine
methyltransferase.
/FTId=PRO_0000139359.
ACT_SITE 145 145 Alkyl group acceptor.
MOD_RES 201 201 Phosphoserine.
VARIANT 30 30 E -> K (in dbSNP:2020893).
/FTId=VAR_014750.
VARIANT 65 65 W -> C (in dbSNP:2282164).
/FTId=VAR_020354.
VARIANT 84 84 L -> F (in dbSNP:12917).
/FTId=VAR_014751.
VARIANT 143 143 I -> V (in dbSNP:2308321).
/FTId=VAR_014752.
VARIANT 160 160 G -> R (in dbSNP:2308318).
/FTId=VAR_014753.
VARIANT 166 166 E -> D (in dbSNP:2308320).
/FTId=VAR_014754.
VARIANT 178 178 K -> R (in dbSNP:2308327).
/FTId=VAR_014755.
CONFLICT 127 127 A -> T (in Ref. 2).
STRAND 8 12
TURN 15 16
STRAND 17 17
STRAND 19 24
TURN 25 26
STRAND 27 33
STRAND 45 46
STRAND 51 52
STRAND 56 56
HELIX 57 71
HELIX 73 78
STRAND 79 79
STRAND 84 84
HELIX 87 90
STRAND 91 91
HELIX 94 105
TURN 108 109
STRAND 112 113
HELIX 114 120
TURN 121 122
TURN 124 125
HELIX 127 134
TURN 135 136
STRAND 138 140
TURN 141 142
STRAND 143 143
HELIX 145 147
STRAND 148 149
TURN 151 152
STRAND 153 153
TURN 159 160
HELIX 162 171
TURN 172 173
Comments:
-!- FUNCTION: Involved in the cellular defense against the biological
effects of O6-methylguanine (O6-MeG) in DNA. Repairs alkylated
guanine in DNA by stoichiometrically transferring the alkyl group
at the O-6 position to a cysteine residue in the enzyme. This is a
suicide reaction: the enzyme is irreversibly inactivated.
-!- CATALYTIC ACTIVITY: DNA (containing 6-O-methylguanine) + protein
L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-
cysteine.
-!- SUBCELLULAR LOCATION: Nucleus.
-!- SIMILARITY: Belongs to the MGMT family.
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Sequence length: 207
MDKDCEMKRT TLDSPLGKLE LSGCEQGLHE IKLLGKGTSA ADAVEVPAPA AVLGGPEPLM
QCTAWLNAYF HQPEAIEEFP VPALHHPVFQ QESFTRQVLW KLLKVVKFGE VISYQQLAAL
AGNPKAARAV GGAMRGNPVP ILIPCHRVVC SSGAVGNYSG GLAVKEWLLA HEGHRLGKPG
LGGSSGLAGA WLKGAGATSG SPPAGRN