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Protein

Methylated-DNA--protein-cysteine methyltransferase

Gene

MGMT

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

Functioni

Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.

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.

Catalytic activityi

DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.PROSITE-ProRule annotation
DNA (containing 4-O-methylthymine) + protein L-cysteine = DNA (without 4-O-methylthymine) + 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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Methyltransferase, Transferase
Biological processDNA damage, DNA repair
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi2.1.1.63 2681
ReactomeiR-HSA-5657655 MGMT-mediated DNA damage reversal
SIGNORiP16455

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

EuPathDBiHostDB:ENSG00000170430.9
HGNCiHGNC:7059 MGMT
MIMi156569 gene
neXtProtiNX_P16455

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
DrugBankiDB04531 Benzylcysteine
DB00151 L-Cysteine
DB02216 S-Methylcysteine

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
ProteomicsDBi53365

PTM databases

iPTMnetiP16455
PhosphoSitePlusiP16455

Expressioni

Gene expression databases

BgeeiENSG00000170430 Expressed in 207 organ(s), highest expression level in liver
CleanExiHS_MGMT
ExpressionAtlasiP16455 baseline and differential
GenevisibleiP16455 HS

Organism-specific databases

HPAiCAB002786
CAB069881
HPA032135
HPA032136
HPA069497

Interactioni

Protein-protein interaction databases

BioGridi110411, 75 interactors
IntActiP16455, 1 interactor
STRINGi9606.ENSP00000302111

Chemistry databases

BindingDBiP16455

Structurei

Secondary structure

1207
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
InterProiView protein in InterPro
IPR001497 MethylDNA_cys_MeTrfase_AS
IPR014048 MethylDNA_cys_MeTrfase_DNA-bd
IPR036217 MethylDNA_cys_MeTrfase_DNAb
IPR008332 MethylG_MeTrfase_N
IPR036631 MGMT_N_sf
IPR036388 WH-like_DNA-bd_sf
PfamiView protein in Pfam
PF01035 DNA_binding_1, 1 hit
PF02870 Methyltransf_1N, 1 hit
SUPFAMiSSF46767 SSF46767, 1 hit
SSF53155 SSF53155, 1 hit
TIGRFAMsiTIGR00589 ogt, 1 hit
PROSITEiView protein in PROSITE
PS00374 MGMT, 1 hit

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 dbSNP:rs2020893Ensembl.1
Natural variantiVAR_05612953L → F. Corresponds to variant dbSNP:rs12917Ensembl.1
Natural variantiVAR_02911258P → S. Corresponds to variant dbSNP:rs2308322Ensembl.1
Natural variantiVAR_02035465W → C. Corresponds to variant dbSNP:rs2282164Ensembl.1
Natural variantiVAR_01475184L → F. Corresponds to variant dbSNP:rs12917Ensembl.1
Natural variantiVAR_056130112I → V. Corresponds to variant dbSNP:rs2308321Ensembl.1
Natural variantiVAR_014752143I → V. Corresponds to variant dbSNP:rs2308321Ensembl.1
Natural variantiVAR_014753160G → R. Corresponds to variant dbSNP:rs2308318Ensembl.1
Natural variantiVAR_014754166E → D. Corresponds to variant dbSNP:rs2308320Ensembl.1
Natural variantiVAR_014755178K → R. Corresponds to variant dbSNP:rs2308327Ensembl.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 Genomic DNA No translation available.
AL355531 Genomic DNA No translation available.
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

Entry informationi

Entry nameiMGMT_HUMAN
AccessioniPrimary (citable) accession number: P16455
Secondary accession number(s): Q5VY78
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: September 12, 2018
This is version 185 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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