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    Mgmt O-6-methylguanine-DNA methyltransferase [ Mus musculus (house mouse) ]

    Gene ID: 17314, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Mgmtprovided by MGI
    Official Full Name
    O-6-methylguanine-DNA methyltransferaseprovided by MGI
    Primary source
    MGI:MGI:96977
    See related
    Ensembl:ENSMUSG00000054612 AllianceGenome:MGI:96977
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    AGT; Agat
    Summary
    Enables methyltransferase activity. Acts upstream of or within DNA dealkylation involved in DNA repair and regulation of cysteine-type endopeptidase activity involved in apoptotic process. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. Is expressed in embryo and forelimb bud. Human ortholog(s) of this gene implicated in several diseases, including carcinoma (multiple); endocrine gland cancer (multiple); granulosa cell tumor; nervous system cancer (multiple); and urinary bladder cancer. Orthologous to human MGMT (O-6-methylguanine-DNA methyltransferase). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Ubiquitous expression in liver adult (RPKM 5.7), subcutaneous fat pad adult (RPKM 5.0) and 24 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    7 F3; 7 82.07 cM
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 7 NC_000073.7 (136496315..136732001)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 7 NC_000073.6 (136894463..137128193)

    Chromosome 7 - NC_000073.7Genomic Context describing neighboring genes Neighboring gene predicted gene 6249 Neighboring gene predicted gene, 29978 Neighboring gene STARR-seq mESC enhancer starr_20376 Neighboring gene 3-phosphoglycerate dehydrogenase pseudogene Neighboring gene STARR-seq mESC enhancer starr_20378 Neighboring gene predicted gene, 39108 Neighboring gene STARR-seq mESC enhancer starr_20380 Neighboring gene STARR-seq mESC enhancer starr_20381 Neighboring gene predicted gene, 30061 Neighboring gene early B cell factor 3 Neighboring gene predicted gene 10578

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Malignant progression in O6-methylguanine-DNA methyltransferase-deficient esophageal cancer cells is associated with Ezrin protein. Su Y, et al. DNA Cell Biol, 2012 May. PMID 22196440
    2. The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner. Kisby GE, et al. PLoS One, 2011. PMID 21731631, Free PMC Article
    3. Mgmt deficiency alters the in vivo mutational spectrum of tissues exposed to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Sandercock LE, et al. Carcinogenesis, 2008 Apr. PMID 18281247
    4. In vivo selection of hematopoietic stem cells transduced at a low multiplicity-of-infection with a foamy viral MGMT(P140K) vector. Cai S, et al. Exp Hematol, 2008 Mar. PMID 18279716, Free PMC Article
    5. Role of O6-methylguanine-DNA methyltransferase in protecting from alkylating agent-induced toxicity and mutations in mice. Hansen RJ, et al. Carcinogenesis, 2007 May. PMID 17116724

    See all (74) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.
      Title: Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma.
    2. Magnetic resonance imaging reveals specific anatomical changes in the brain of Agat- and Gamt-mice attributed to creatine depletion and guanidinoacetate alteration.
      Title: Magnetic resonance imaging reveals specific anatomical changes in the brain of Agat- and Gamt-mice attributed to creatine depletion and guanidinoacetate alteration.
    3. Muscle phenotype of AGAT- and GAMT-deficient mice after simvastatin exposure.
      Title: Muscle phenotype of AGAT- and GAMT-deficient mice after simvastatin exposure.
    4. This study shows that when cell death and cell cycle arrest pathways are inhibited, p53 can still mediate MGMT-dependent repair, to promote cell survival upon DNA damage.
      Title: The proline rich domain of p53 is dispensable for MGMT-dependent DNA repair and cell survival following alkylation damage.
    5. Snell, GHKRO, and PAPPA-KO mice express high levels of two proteins involved in DNA repair, O-6-methylguanine-DNA methyltransferase (MGMT) and N-myc downstream-regulated gene 1 (NDRG1).
      Title: mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice.
    6. This study demonstrates for the first time a non-linear dose-response for alkylation-induced colorectal carcinogenesis and reveals DNA repair by MGMT, but not AAG, as a key node in determining a carcinogenic threshold.
      Title: DNA repair by MGMT, but not AAG, causes a threshold in alkylation-induced colorectal carcinogenesis.
    7. Findings suggest that O6-methylguanine-DNA methyltransferase (MGMT)-mediated temozolomide resistance is associated with increased histone acetylation.
      Title: Inhibition of histone deacetylation potentiates the evolution of acquired temozolomide resistance linked to MGMT upregulation in glioblastoma xenografts.
    8. Loss of MGMT expression and high Ezrin protein expression leads to esophageal cancer.
      Title: Malignant progression in O6-methylguanine-DNA methyltransferase-deficient esophageal cancer cells is associated with Ezrin protein.
    9. Both base excision repair and O6-methylguanine-DNA methyltransferase protect against methylation-induced colon carcinogenesis.
      Title: Both base excision repair and O6-methylguanine-DNA methyltransferase protect against methylation-induced colon carcinogenesis.
    10. ta indicate that Zik1 and Gja9 demonstrated cancer-specific aberrant DNA methylation, whereas, Cdkn2a/p16, Igfbp3, Mgmt, Id4, and Cxcr4 were methylated in both the AOM tumors and normal colon mucosa.
      Title: Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Gene trapped (1) 
    • Targeted (5)  1 citation
    • Endonuclease-mediated (3) 

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC107020

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium ion binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables catalytic activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables methylated-DNA-[protein]-cysteine S-methyltransferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables methylated-DNA-[protein]-cysteine S-methyltransferase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables methyltransferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within DNA alkylation repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA alkylation repair ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within DNA damage response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within methylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of apoptotic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of DNA repair ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of double-strand break repair ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within regulation of cysteine-type endopeptidase activity involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in nucleoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    methylated-DNA--protein-cysteine methyltransferase
    Names
    6-O-methylguanine-DNA methyltransferase
    O-6-alkylguanine-DNA alkyltransferase
    O-6-methylguanine-DNA-alkyltransferase
    NP_001363966.1
    NP_001399626.1
    NP_001399627.1
    NP_001399628.1
    NP_001399629.1
    NP_001399630.1
    NP_001399631.1
    NP_001399632.1
    NP_001399633.1
    NP_032624.1
    XP_006507472.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001377037.2 → NP_001363966.1  methylated-DNA--protein-cysteine methyltransferase isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC132594, AC135639, AC148997
      UniProtKB/Swiss-Prot
      P26187, Q54A49
      UniProtKB/TrEMBL
      Q4VA39
      Conserved Domains (1) summary
      COG0350
      Location:6 → 178
      AdaB; O6-methylguanine-DNA--protein-cysteine methyltransferase [Replication, recombination and repair]

    2. NM_001412697.1 → NP_001399626.1  methylated-DNA--protein-cysteine methyltransferase isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC132594, AC135639, AC148997

    3. NM_001412698.1 → NP_001399627.1  methylated-DNA--protein-cysteine methyltransferase isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    4. NM_001412699.1 → NP_001399628.1  methylated-DNA--protein-cysteine methyltransferase isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    5. NM_001412700.1 → NP_001399629.1  methylated-DNA--protein-cysteine methyltransferase isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    6. NM_001412701.1 → NP_001399630.1  methylated-DNA--protein-cysteine methyltransferase isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    7. NM_001412702.1 → NP_001399631.1  methylated-DNA--protein-cysteine methyltransferase isoform 4

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    8. NM_001412703.1 → NP_001399632.1  methylated-DNA--protein-cysteine methyltransferase isoform 5

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    9. NM_001412704.1 → NP_001399633.1  methylated-DNA--protein-cysteine methyltransferase isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC132594, AC135639, AC148997
      UniProtKB/Swiss-Prot
      P26187, Q54A49

    10. NM_008598.4 → NP_032624.1  methylated-DNA--protein-cysteine methyltransferase isoform 1

      See identical proteins and their annotated locations for NP_032624.1

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997
      Consensus CDS
      CCDS21945.1
      UniProtKB/Swiss-Prot
      P26187, Q54A49
      UniProtKB/TrEMBL
      Q4VA39
      Related
      ENSMUSP00000080224.3, ENSMUST00000081510.4
      Conserved Domains (1) summary
      COG0350
      Location:6 → 178
      AdaB; O6-methylguanine-DNA--protein-cysteine methyltransferase [Replication, recombination and repair]

    RNA

    1. NR_182026.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    2. NR_182027.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    3. NR_182028.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC132122, AC132594, AC135639, AC148997

    4. NR_182029.1 RNA Sequence

      Status: VALIDATED

      Source sequence(s)
      AC132594, AC135639, AC148997

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000073.7 Reference GRCm39 C57BL/6J

      Range
      136496315..136732001
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006507409.4 → XP_006507472.1  methylated-DNA--protein-cysteine methyltransferase isoform X4

      See identical proteins and their annotated locations for XP_006507472.1

      UniProtKB/Swiss-Prot
      P26187, Q54A49
      UniProtKB/TrEMBL
      Q4VA39
      Conserved Domains (1) summary
      COG0350
      Location:6 → 178
      AdaB; O6-methylguanine-DNA--protein-cysteine methyltransferase [Replication, recombination and repair]
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P26187.3 GenPept UniProtKB/Swiss-Prot:P26187

    Gene LinkOut

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