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P16455 (MGMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methylated-DNA--protein-cysteine methyltransferase

EC=2.1.1.63
Alternative name(s):
6-O-methylguanine-DNA methyltransferase
Short name=MGMT
O-6-methylguanine-DNA-alkyltransferase
Gene names
Name:MGMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length207 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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.

Cofactor

Binds 1 zinc ion.

Subcellular location

Nucleus.

Miscellaneous

This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocatalyst that acts repeatedly and over many reaction cycles.

Sequence similarities

Belongs to the MGMT family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionMethyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA dealkylation involved in DNA repair

Inferred from electronic annotation. Source: Ensembl

DNA ligation

Traceable author statement Ref.2. Source: ProtInc

DNA methylation

Traceable author statement Ref.1. Source: GOC

DNA repair

Traceable author statement. Source: Reactome

cellular response to ionizing radiation

Inferred from electronic annotation. Source: Ensembl

cellular response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

cellular response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

mammary gland epithelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA repair

Inferred from electronic annotation. Source: Ensembl

regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to folic acid

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement Ref.2. Source: ProtInc

   Molecular_functionDNA binding

Traceable author statement Ref.2. Source: ProtInc

DNA-methyltransferase activity

Traceable author statement Ref.1. Source: ProtInc

calcium ion binding

Inferred from electronic annotation. Source: Ensembl

methylated-DNA-[protein]-cysteine S-methyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

methyltransferase activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 207207Methylated-DNA--protein-cysteine methyltransferase
PRO_0000139359

Sites

Active site1451Nucleophile; methyl group acceptor
Metal binding51Zinc
Metal binding241Zinc
Metal binding291Zinc
Metal binding851Zinc
Binding site951DNA; via amide nitrogen
Binding site1141DNA
Binding site1151DNA; via amide nitrogen
Binding site1231DNA
Binding site1281DNA
Binding site1511DNA; via amide nitrogen

Natural variations

Natural variant301E → K.
Corresponds to variant rs2020893 [ dbSNP | Ensembl ].
VAR_014750
Natural variant531L → F.
Corresponds to variant rs12917 [ dbSNP | Ensembl ].
VAR_056129
Natural variant581P → S.
Corresponds to variant rs2308322 [ dbSNP | Ensembl ].
VAR_029112
Natural variant651W → C.
Corresponds to variant rs2282164 [ dbSNP | Ensembl ].
VAR_020354
Natural variant841L → F.
Corresponds to variant rs12917 [ dbSNP | Ensembl ].
VAR_014751
Natural variant1121I → V.
Corresponds to variant rs2308321 [ dbSNP | Ensembl ].
VAR_056130
Natural variant1431I → V.
Corresponds to variant rs2308321 [ dbSNP | Ensembl ].
VAR_014752
Natural variant1601G → R.
Corresponds to variant rs2308318 [ dbSNP | Ensembl ].
VAR_014753
Natural variant1661E → D.
Corresponds to variant rs2308320 [ dbSNP | Ensembl ].
VAR_014754
Natural variant1781K → R.
Corresponds to variant rs2308327 [ dbSNP | Ensembl ].
VAR_014755

Experimental info

Mutagenesis1141Y → A: Decreases activity towards methylated DNA over 1000-fold. Slightly reduced reactivity with O6-benzylguanine. Ref.12
Mutagenesis1141Y → E: Loss of DNA repair activity. Slightly reduced reactivity with O6-benzylguanine. Ref.12
Mutagenesis1281R → A or D: Decreases activity towards methylated DNA over 1000-fold. No effect on reactivity with O6-benzylguanine. Ref.12 Ref.14
Mutagenesis1281R → G: Loss of DNA repair activity. Ref.12 Ref.14
Mutagenesis1281R → K or L: Slightly reduced DNA repair activity. Ref.12 Ref.14
Mutagenesis1381P → K: Decreased reactivity with O6-benzylguanine. Ref.11
Mutagenesis1401P → A: Decreased reactivity with O6-benzylguanine. Ref.11
Mutagenesis1451C → A: Loss of DNA repair activity. Ref.12 Ref.14
Mutagenesis1561G → A: Decreased reactivity with O6-benzylguanine. Ref.11
Mutagenesis1581Y → A: Reduced DNA repair activity. Decreased reactivity with O6-benzylguanine. Ref.13
Mutagenesis1581Y → F: Slightly reduced DNA repair activity. Ref.13
Sequence conflict1271A → T in AAA52317. Ref.2

Secondary structure

............................ 207
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16455 [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: 76BBF19DFC4512D6

FASTA20721,646
        10         20         30         40         50         60 
MDKDCEMKRT TLDSPLGKLE LSGCEQGLHE IKLLGKGTSA ADAVEVPAPA AVLGGPEPLM 

        70         80         90        100        110        120 
QCTAWLNAYF HQPEAIEEFP VPALHHPVFQ QESFTRQVLW KLLKVVKFGE VISYQQLAAL 

       130        140        150        160        170        180 
AGNPKAARAV GGAMRGNPVP ILIPCHRVVC SSGAVGNYSG GLAVKEWLLA HEGHRLGKPG 

       190        200 
LGGSSGLAGA WLKGAGATSG SPPAGRN 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and structural characterization of a cDNA clone encoding the human DNA repair protein for O6-alkylguanine."
Tano K., Shiota S., Collier J., Foote R.S., Mitra S.
Proc. Natl. Acad. Sci. U.S.A. 87:686-690(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-8.
[2]"cDNA cloning and chromosomal assignment of the human O6-methylguanine-DNA methyltransferase. cDNA expression in Escherichia coli and gene expression in human cells."
Rydberg B., Spurr N., Karran P.
J. Biol. Chem. 265:9563-9569(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Purification, structure, and biochemical properties of human O6-methylguanine-DNA methyltransferase."
Koike G., Maki H., Takeya H., Hayakawa H., Sekiguchi M.
J. Biol. Chem. 265:14754-14762(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Expression and cloning of complementary DNA for a human enzyme that repairs O6-methylguanine in DNA."
Hayakawa H., Koike G., Sekiguchi M.
J. Mol. Biol. 213:739-747(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[9]"Structural and immunological comparison of indigenous human O6-methylguanine-DNA methyltransferase with that encoded by a cloned cDNA."
von Wronski M.A., Shiota S., Tano K., Mitra S., Bigner D.D., Brent T.P.
J. Biol. Chem. 266:1064-1070(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, ALKYL GROUP ACCEPTOR.
[10]"Specificities of human, rat and E. coli O6-methylguanine-DNA methyltransferases towards the repair of O6-methyl and O6-ethylguanine in DNA."
Liem L.-K., Lim A., Li B.F.L.
Nucleic Acids Res. 22:1613-1619(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[11]"Mutations in human O6-alkylguanine-DNA alkyltransferase imparting resistance to O6-benzylguanine."
Crone T.M., Goodtzova K., Edara S., Pegg A.E.
Cancer Res. 54:6221-6227(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-138; PRO-140 AND GLY-156.
[12]"Alteration of arginine-128 to alanine abolishes the ability of human O6-alkylguanine-DNA alkyltransferase to repair methylated DNA but has no effect on its reaction with O6-benzylguanine."
Kanugula S., Goodtzova K., Edara S., Pegg A.E.
Biochemistry 34:7113-7119(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TYR-114; ARG-128 AND CYS-145.
[13]"The role of tyrosine-158 in O6-alkylguanine-DNA alkyltransferase activity."
Edara S., Goodtzova K., Pegg A.E.
Carcinogenesis 16:1637-1642(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF TYR-158.
[14]"Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding."
Daniels D.S., Mol C.D., Arvai A.S., Kanugula S., Pegg A.E., Tainer J.A.
EMBO J. 19:1719-1730(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH DNA AND ZINC IONS, MUTAGENESIS OF ARG-128 AND CYS-145.
[15]"Crystal structure of the human O(6)-alkylguanine-DNA alkyltransferase."
Wibley J.E., Pegg A.E., Moody P.C.
Nucleic Acids Res. 28:393-401(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-176.
[16]"The structure of the human AGT protein bound to DNA and its implications for damage detection."
Duguid E.M., Rice P.A., He C.
J. Mol. Biol. 350:657-666(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-179 IN COMPLEX WITH DNA AND ZINC IONS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X54228 mRNA. Translation: CAA38137.1.
M29971 mRNA. Translation: AAA59596.1.
M31767 mRNA. Translation: AAA52317.1.
M60761 mRNA. Translation: AAA59594.1.
BT006714 mRNA. Translation: AAP35360.1.
AL157832, AL355531 Genomic DNA. Translation: CAH70060.1.
AL355531, AL157832 Genomic DNA. Translation: CAH72190.1.
CH471066 Genomic DNA. Translation: EAW49166.1.
BC000824 mRNA. Translation: AAH00824.1.
PIRXUHUMC. A34889.
RefSeqXP_005252739.1. XM_005252682.1.
UniGeneHs.501522.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EH6X-ray2.00A1-207[»]
1EH7X-ray2.00A1-207[»]
1EH8X-ray2.50A1-207[»]
1QNTX-ray1.90A1-176[»]
1T38X-ray3.20A1-176[»]
1T39X-ray3.30A/B1-176[»]
1YFHX-ray3.01A/B/C1-179[»]
ProteinModelPortalP16455.
SMRP16455. Positions 6-176.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP16455. 1 interaction.
MINTMINT-5002466.
STRING9606.ENSP00000302111.

Chemistry

BindingDBP16455.
ChEMBLCHEMBL2864.
DrugBankDB00151. L-Cysteine.

PTM databases

PhosphoSiteP16455.

Polymorphism databases

DMDM127069.

Proteomic databases

MaxQBP16455.
PaxDbP16455.
PeptideAtlasP16455.
PRIDEP16455.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000306010; ENSP00000302111; ENSG00000170430.
GeneID4255.
KEGGhsa:4255.

Organism-specific databases

CTD4255.
GeneCardsGC10P131195.
H-InvDBHIX0009309.
HGNCHGNC:7059. MGMT.
HPACAB002786.
MIM156569. gene.
neXtProtNX_P16455.
Orphanet251579. Giant cell glioblastoma.
251576. Gliosarcoma.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0350.
HOGENOMHOG000244137.
HOVERGENHBG001146.
InParanoidP16455.
KOK00567.
OrthoDBEOG7RRF9D.
PhylomeDBP16455.
TreeFamTF314064.

Enzyme and pathway databases

BRENDA2.1.1.63. 2681.
ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressP16455.
BgeeP16455.
CleanExHS_MGMT.
GenevestigatorP16455.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001497. MethylDNA_cys_MeTrfase_AS.
IPR014048. MethylDNA_cys_MeTrfase_DNA-bd.
IPR008332. MethylG_MeTrfase_N.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF01035. DNA_binding_1. 1 hit.
PF02870. Methyltransf_1N. 1 hit.
[Graphical view]
SUPFAMSSF46767. SSF46767. 1 hit.
SSF53155. SSF53155. 1 hit.
TIGRFAMsTIGR00589. ogt. 1 hit.
PROSITEPS00374. MGMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16455.
GeneWikiO-6-methylguanine-DNA_methyltransferase.
GenomeRNAi4255.
PROP16455.
SOURCESearch...

Entry information

Entry nameMGMT_HUMAN
AccessionPrimary (citable) accession number: P16455
Secondary accession number(s): Q5VY78
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: May 14, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM