MGMT

Protein identityUniProt · HPA

UniProt accession

P16455

Gene

MGMT

Ensembl

ENSG00000170430

Chromosome

10

Canonical length

207 aa

Protein class

Cancer-related genes, Enzymes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

Alkylating agents are potent carcinogens that can result in cell death, mutation and cancer. The protein encoded by this gene is a DNA repair protein that is involved in cellular defense against mutagenesis and toxicity from alkylating agents. The protein catalyzes transfer of methyl groups from O(6)-alkylguanine and other methylated moieties of the DNA to its own molecule, which repairs the toxic lesions. Methylation of the genes promoter has been associated with several cancer types, including colorectal cancer, lung cancer, lymphoma and glioblastoma. [provided by RefSeq, Sep 2015]

Canonical amino-acid sequenceUniProt

207 residues, UniProt reviewed canonical sequence.

>P16455|MGMT
     1  MDKDCEMKRT TLDSPLGKLE LSGCEQGLHE IKLLGKGTSA ADAVEVPAPA AVLGGPEPLM
    61  QCTAWLNAYF HQPEAIEEFP VPALHHPVFQ QESFTRQVLW KLLKVVKFGE VISYQQLAAL
   121  AGNPKAARAV GGAMRGNPVP ILIPCHRVVC SSGAVGNYSG GLAVKEWLLA HEGHRLGKPG
   181  LGGSSGLAGA WLKGAGATSG SPPAGRN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MGMT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

126 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for MGMT from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.78

gnomAD pLI

0

gnomAD missense Z

-0.62

DepMap mean gene effect

0.09

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• DNA alkylation repair
• DNA repair
• methylation
• negative regulation of apoptotic process
• positive regulation of double-strand break repair

Molecular functions

• DNA binding
• DNA-methyltransferase activity
• metal ion binding
• methyltransferase activity
• methylated-DNA-[protein]-cysteine S-methyltransferase activity

Cellular components

• membrane
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Winged helix-like DNA-binding domain superfamily
• Methylated-DNA-[protein]-cysteine S-methyltransferase, active site
• Methylguanine DNA methyltransferase, ribonuclease-like domain
• Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding
• Methylated DNA-protein cysteine methyltransferase, DNA binding domain
• Methylated DNA-protein cysteine methyltransferase domain superfamily
• 6-O-methylguanine DNA methyltransferase, DNA binding domain
• 6-O-methylguanine DNA methyltransferase, ribonuclease-like domain

KeywordsUniProt

• DNA damage
• DNA repair
• DNA-binding
• Metal-binding
• Methyltransferase
• Nucleus
• Phosphoprotein
• Transferase
• Zinc