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Protein

Methylated-DNA--protein-cysteine methyltransferase

Gene

MGMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 activityi

DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.PROSITE-ProRule annotation

Cofactori

Zn2+Note: Binds 1 zinc ion.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi5Zinc1
Metal bindingi24Zinc1
Metal bindingi29Zinc1
Metal bindingi85Zinc1
Binding sitei95DNA; via amide nitrogen2 Publications1
Binding sitei114DNA2 Publications1
Binding sitei115DNA; via amide nitrogen2 Publications1
Binding sitei123DNA2 Publications1
Binding sitei128DNA2 Publications1
Active sitei145Nucleophile; methyl group acceptor1
Binding sitei151DNA; via amide nitrogen2 Publications1

GO - Molecular functioni

  • calcium ion binding Source: Ensembl
  • damaged DNA binding Source: GO_Central
  • DNA binding Source: ProtInc
  • DNA-methyltransferase activity Source: ProtInc
  • methylated-DNA-[protein]-cysteine S-methyltransferase activity Source: GO_Central
  • methyltransferase activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS10127-MONOMER.
BRENDAi2.1.1.63. 2681.
ReactomeiR-HSA-5657655. MGMT-mediated DNA damage reversal.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:MGMT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:7059. MGMT.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi114Y → A: Decreases activity towards methylated DNA over 1000-fold. Slightly reduced reactivity with O6-benzylguanine. 1 Publication1
Mutagenesisi114Y → E: Loss of DNA repair activity. Slightly reduced reactivity with O6-benzylguanine. 1 Publication1
Mutagenesisi128R → A or D: Decreases activity towards methylated DNA over 1000-fold. No effect on reactivity with O6-benzylguanine. 2 Publications1
Mutagenesisi128R → G: Loss of DNA repair activity. 2 Publications1
Mutagenesisi128R → K or L: Slightly reduced DNA repair activity. 2 Publications1
Mutagenesisi138P → K: Decreased reactivity with O6-benzylguanine. 1 Publication1
Mutagenesisi140P → A: Decreased reactivity with O6-benzylguanine. 1 Publication1
Mutagenesisi145C → A: Loss of DNA repair activity. 2 Publications1
Mutagenesisi156G → A: Decreased reactivity with O6-benzylguanine. 1 Publication1
Mutagenesisi158Y → A: Reduced DNA repair activity. Decreased reactivity with O6-benzylguanine. 1 Publication1
Mutagenesisi158Y → F: Slightly reduced DNA repair activity. 1 Publication1

Organism-specific databases

DisGeNETi4255.
MalaCardsiMGMT.
Orphaneti251579. Giant cell glioblastoma.
251576. Gliosarcoma.

Chemistry databases

ChEMBLiCHEMBL2864.
DrugBankiDB00151. L-Cysteine.

Polymorphism and mutation databases

DMDMi127069.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001393591 – 207Methylated-DNA--protein-cysteine methyltransferaseAdd BLAST207

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14PhosphoserineCombined sources1
Modified residuei201PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP16455.
MaxQBiP16455.
PaxDbiP16455.
PeptideAtlasiP16455.
PRIDEiP16455.

PTM databases

iPTMnetiP16455.
PhosphoSitePlusiP16455.

Expressioni

Gene expression databases

BgeeiENSG00000170430.
CleanExiHS_MGMT.
ExpressionAtlasiP16455. baseline and differential.
GenevisibleiP16455. HS.

Organism-specific databases

HPAiCAB002786.
HPA032135.
HPA032136.

Interactioni

Protein-protein interaction databases

BioGridi110411. 74 interactors.
IntActiP16455. 1 interactor.
MINTiMINT-5002466.
STRINGi9606.ENSP00000302111.

Chemistry databases

BindingDBiP16455.

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 12Combined sources5
Beta strandi19 – 24Combined sources6
Beta strandi27 – 33Combined sources7
Beta strandi50 – 52Combined sources3
Helixi57 – 71Combined sources15
Helixi73 – 78Combined sources6
Helixi87 – 90Combined sources4
Helixi94 – 105Combined sources12
Helixi114 – 120Combined sources7
Turni124 – 126Combined sources3
Helixi127 – 134Combined sources8
Beta strandi138 – 140Combined sources3
Helixi145 – 147Combined sources3
Helixi162 – 171Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP16455.
SMRiP16455.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16455.

Family & Domainsi

Sequence similaritiesi

Belongs to the MGMT family.Curated

Phylogenomic databases

eggNOGiKOG4062. Eukaryota.
COG0350. LUCA.
HOGENOMiHOG000244137.
HOVERGENiHBG001146.
InParanoidiP16455.
OrthoDBiEOG091G11SR.
PhylomeDBiP16455.
TreeFamiTF314064.

Family and domain databases

CDDicd06445. ATase. 1 hit.
Gene3Di1.10.10.10. 1 hit.
InterProiIPR001497. MethylDNA_cys_MeTrfase_AS.
IPR014048. MethylDNA_cys_MeTrfase_DNA-bd.
IPR008332. MethylG_MeTrfase_N.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF01035. DNA_binding_1. 1 hit.
PF02870. Methyltransf_1N. 1 hit.
[Graphical view]
SUPFAMiSSF46767. SSF46767. 1 hit.
SSF53155. SSF53155. 1 hit.
TIGRFAMsiTIGR00589. ogt. 1 hit.
PROSITEiPS00374. MGMT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P16455-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDKDCEMKRT TLDSPLGKLE LSGCEQGLHE IKLLGKGTSA ADAVEVPAPA
60 70 80 90 100
AVLGGPEPLM QCTAWLNAYF HQPEAIEEFP VPALHHPVFQ QESFTRQVLW
110 120 130 140 150
KLLKVVKFGE VISYQQLAAL AGNPKAARAV GGAMRGNPVP ILIPCHRVVC
160 170 180 190 200
SSGAVGNYSG GLAVKEWLLA HEGHRLGKPG LGGSSGLAGA WLKGAGATSG

SPPAGRN
Length:207
Mass (Da):21,646
Last modified:August 1, 1990 - v1
Checksum:i76BBF19DFC4512D6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127A → T in AAA52317 (PubMed:2188979).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01475030E → K.Corresponds to variant rs2020893dbSNPEnsembl.1
Natural variantiVAR_05612953L → F.Corresponds to variant rs12917dbSNPEnsembl.1
Natural variantiVAR_02911258P → S.Corresponds to variant rs2308322dbSNPEnsembl.1
Natural variantiVAR_02035465W → C.Corresponds to variant rs2282164dbSNPEnsembl.1
Natural variantiVAR_01475184L → F.Corresponds to variant rs12917dbSNPEnsembl.1
Natural variantiVAR_056130112I → V.Corresponds to variant rs2308321dbSNPEnsembl.1
Natural variantiVAR_014752143I → V.Corresponds to variant rs2308321dbSNPEnsembl.1
Natural variantiVAR_014753160G → R.Corresponds to variant rs2308318dbSNPEnsembl.1
Natural variantiVAR_014754166E → D.Corresponds to variant rs2308320dbSNPEnsembl.1
Natural variantiVAR_014755178K → R.Corresponds to variant rs2308327dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA34889. XUHUMC.
RefSeqiXP_005252739.1. XM_005252682.2.
UniGeneiHs.501522.

Genome annotation databases

EnsembliENST00000306010; ENSP00000302111; ENSG00000170430.
GeneIDi4255.
UCSCiuc001lkh.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiA34889. XUHUMC.
RefSeqiXP_005252739.1. XM_005252682.2.
UniGeneiHs.501522.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP16455.
SMRiP16455.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110411. 74 interactors.
IntActiP16455. 1 interactor.
MINTiMINT-5002466.
STRINGi9606.ENSP00000302111.

Chemistry databases

BindingDBiP16455.
ChEMBLiCHEMBL2864.
DrugBankiDB00151. L-Cysteine.

PTM databases

iPTMnetiP16455.
PhosphoSitePlusiP16455.

Polymorphism and mutation databases

DMDMi127069.

Proteomic databases

EPDiP16455.
MaxQBiP16455.
PaxDbiP16455.
PeptideAtlasiP16455.
PRIDEiP16455.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306010; ENSP00000302111; ENSG00000170430.
GeneIDi4255.
UCSCiuc001lkh.3. human.

Organism-specific databases

CTDi4255.
DisGeNETi4255.
GeneCardsiMGMT.
H-InvDBHIX0009309.
HGNCiHGNC:7059. MGMT.
HPAiCAB002786.
HPA032135.
HPA032136.
MalaCardsiMGMT.
MIMi156569. gene.
neXtProtiNX_P16455.
Orphaneti251579. Giant cell glioblastoma.
251576. Gliosarcoma.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4062. Eukaryota.
COG0350. LUCA.
HOGENOMiHOG000244137.
HOVERGENiHBG001146.
InParanoidiP16455.
OrthoDBiEOG091G11SR.
PhylomeDBiP16455.
TreeFamiTF314064.

Enzyme and pathway databases

BioCyciZFISH:HS10127-MONOMER.
BRENDAi2.1.1.63. 2681.
ReactomeiR-HSA-5657655. MGMT-mediated DNA damage reversal.

Miscellaneous databases

ChiTaRSiMGMT. human.
EvolutionaryTraceiP16455.
GeneWikiiO-6-methylguanine-DNA_methyltransferase.
GenomeRNAii4255.
PROiP16455.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170430.
CleanExiHS_MGMT.
ExpressionAtlasiP16455. baseline and differential.
GenevisibleiP16455. HS.

Family and domain databases

CDDicd06445. ATase. 1 hit.
Gene3Di1.10.10.10. 1 hit.
InterProiIPR001497. MethylDNA_cys_MeTrfase_AS.
IPR014048. MethylDNA_cys_MeTrfase_DNA-bd.
IPR008332. MethylG_MeTrfase_N.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF01035. DNA_binding_1. 1 hit.
PF02870. Methyltransf_1N. 1 hit.
[Graphical view]
SUPFAMiSSF46767. SSF46767. 1 hit.
SSF53155. SSF53155. 1 hit.
TIGRFAMsiTIGR00589. ogt. 1 hit.
PROSITEiPS00374. MGMT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMGMT_HUMAN
AccessioniPrimary (citable) accession number: P16455
Secondary accession number(s): Q5VY78
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 2, 2016
This is version 176 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.