LOCUS       NM_002412               4678 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens O-6-methylguanine-DNA methyltransferase (MGMT), mRNA.
ACCESSION   NM_002412
VERSION     NM_002412.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4678)
  AUTHORS   Huang,G., Ouyang,M., Xiao,K., Zhou,H., Zhong,Z., Long,S., Li,Z.,
            Zhang,Y., Li,L., Xiang,S. and Ding,X.
  TITLE     AP-2alpha decreases TMZ resistance of recurrent GBM by
            downregulating MGMT expression and improving DNA damage
  JOURNAL   Life Sci 357, 123111 (2024)
   PUBMED   39369843
  REMARK    GeneRIF: AP-2alpha decreases TMZ resistance of recurrent GBM by
            downregulating MGMT expression and improving DNA damage.
REFERENCE   2  (bases 1 to 4678)
  AUTHORS   Xu,J., Lou,X., Wang,F., Zhang,W., Xu,X., Ye,Z., Zhuo,Q., Wang,Y.,
            Jing,D., Fan,G., Chen,X., Zhang,Y., Zhou,C., Chen,J., Qin,Y., Yu,X.
            and Ji,S.
  TITLE     MEN1 Deficiency-Driven Activation of the beta-Catenin-MGMT Axis
            Promotes Pancreatic Neuroendocrine Tumor Growth and Confers
            Temozolomide Resistance
  JOURNAL   Adv Sci (Weinh) 11 (35), e2308417 (2024)
   PUBMED   39041891
  REMARK    GeneRIF: MEN1 Deficiency-Driven Activation of the beta-Catenin-MGMT
            Axis Promotes Pancreatic Neuroendocrine Tumor Growth and Confers
            Temozolomide Resistance.
REFERENCE   3  (bases 1 to 4678)
  AUTHORS   Schmitz,E., Guo,Y. and Wang,J.
  TITLE     Adaptive fine-tuning based transfer learning for the identification
            of MGMT promoter methylation status
  JOURNAL   Biomed Phys Eng Express 10 (5), 055018 (2024)
   PUBMED   39029475
  REMARK    GeneRIF: Adaptive fine-tuning based transfer learning for the
            identification of MGMT promoter methylation status.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4678)
  AUTHORS   Kurdi,M., Alkhotani,A., Sabbagh,A., Faizo,E., Lary,A.I.,
            Bamaga,A.K., Almansouri,M., Hafiz,B., Alsharif,T. and Baeesa,S.
  TITLE     The interplay mechanism between IDH mutation, MGMT-promoter
            methylation, and PRMT5 activity in the progression of grade 4
            astrocytoma: unraveling the complex triad theory
  JOURNAL   Oncol Res 32 (6), 1037-1045 (2024)
   PUBMED   38827324
  REMARK    GeneRIF: The interplay mechanism between IDH mutation,
            MGMT-promoter methylation, and PRMT5 activity in the progression of
            grade 4 astrocytoma: unraveling the complex triad theory.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 4678)
  AUTHORS   Al-Moghrabi,N., Al-Showimi,M., Alqahtani,A., Almalik,O.,
            Alhusaini,H., Almalki,G., Saad,A. and Alsunayi,E.
  TITLE     Constitutional BRCA1 and MGMT Methylation Are Significant Risk
            Factors for Triple-Negative Breast Cancer and High-Grade Serous
            Ovarian Cancer in Saudi Women
  JOURNAL   Int J Mol Sci 25 (6), 3108 (2024)
   PUBMED   38542081
  REMARK    GeneRIF: Constitutional BRCA1 and MGMT Methylation Are Significant
            Risk Factors for Triple-Negative Breast Cancer and High-Grade
            Serous Ovarian Cancer in Saudi Women.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4678)
  AUTHORS   Ayi,T.C., Loh,K.C., Ali,R.B. and Li,B.F.
  TITLE     Intracellular localization of human DNA repair enzyme
            methylguanine-DNA methyltransferase by antibodies and its
            importance
  JOURNAL   Cancer Res 52 (23), 6423-6430 (1992)
   PUBMED   1384961
REFERENCE   7  (bases 1 to 4678)
  AUTHORS   Slupphaug,G., Lettrem,I., Myrnes,B. and Krokan,H.E.
  TITLE     Expression of O6-methylguanine--DNA methyltransferase and
            uracil--DNA glycosylase in human placentae from smokers and
            non-smokers
  JOURNAL   Carcinogenesis 13 (10), 1769-1773 (1992)
   PUBMED   1423836
REFERENCE   8  (bases 1 to 4678)
  AUTHORS   Lee,S.M., Crowther,D., Scarffe,J.H., Dougal,M., Elder,R.H.,
            Rafferty,J.A. and Margison,G.P.
  TITLE     Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase
            activity in peripheral lymphocytes of patients undergoing bone
            marrow transplantation
  JOURNAL   Br J Cancer 66 (2), 331-336 (1992)
   PUBMED   1387001
REFERENCE   9  (bases 1 to 4678)
  AUTHORS   Wani,G., Wani,A.A. and D'Ambrosio,S.M.
  TITLE     In situ hybridization of human kidney tissue reveals
            cell-type-specific expression of the O6-methylguanine-DNA
            methyltransferase gene
  JOURNAL   Carcinogenesis 13 (3), 463-468 (1992)
   PUBMED   1547538
REFERENCE   10 (bases 1 to 4678)
  AUTHORS   Natarajan,A.T., Vermeulen,S., Darroudi,F., Valentine,M.B.,
            Brent,T.P., Mitra,S. and Tano,K.
  TITLE     Chromosomal localization of human O6-methylguanine-DNA
            methyltransferase (MGMT) gene by in situ hybridization
  JOURNAL   Mutagenesis 7 (1), 83-85 (1992)
   PUBMED   1635460
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK293593.1 and AL157832.14.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 25, 2018 this sequence version replaced NM_002412.4.
            
            Summary: 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].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803617.140741.1,
                                           SRR14038194.2278050.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000651593.1/ ENSP00000498729.1
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1315              AK293593.1         28-1342
            1316-4678           AL157832.14        75888-79250
FEATURES             Location/Qualifiers
     source          1..4678
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10q26.3"
     gene            1..4678
                     /gene="MGMT"
                     /note="O-6-methylguanine-DNA methyltransferase"
                     /db_xref="GeneID:4255"
                     /db_xref="HGNC:HGNC:7059"
                     /db_xref="MIM:156569"
     exon            1..56
                     /gene="MGMT"
                     /inference="alignment:Splign:2.1.0"
     exon            57..193
                     /gene="MGMT"
                     /inference="alignment:Splign:2.1.0"
     CDS             69..692
                     /gene="MGMT"
                     /EC_number="2.1.1.63"
                     /note="methylguanine-DNA methyltransferase;
                     O6-methylguanine-DNA methyltransferase;
                     O-6-methylguanine-DNA-alkyltransferase;
                     6-O-methylguanine-DNA methyltransferase"
                     /codon_start=1
                     /product="methylated-DNA--protein-cysteine
                     methyltransferase"
                     /protein_id="NP_002403.3"
                     /db_xref="CCDS:CCDS7660.3"
                     /db_xref="GeneID:4255"
                     /db_xref="HGNC:HGNC:7059"
                     /db_xref="MIM:156569"
                     /translation="MDKDCEMKRTTLDSPLGKLELSGCEQGLHEIKLLGKGTSAADAV
                     EVPAPAAVLGGPEPLMQCTAWLNAYFHQPEAIEEFPVPALHHPVFQQESFTRQVLWKL
                     LKVVKFGEVISYQQLAALAGNPKAARAVGGAMRGNPVPILIPCHRVVCSSGAVGNYSG
                     GLAVKEWLLAHEGHRLGKPGLGGSSGLAGAWLKGAGATSGSPPAGRN"
     exon            194..342
                     /gene="MGMT"
                     /inference="alignment:Splign:2.1.0"
     exon            343..482
                     /gene="MGMT"
                     /inference="alignment:Splign:2.1.0"
     exon            483..4678
                     /gene="MGMT"
                     /inference="alignment:Splign:2.1.0"
     regulatory      772..777
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MGMT"
                     /note="hexamer: ATTAAA"
     polyA_site      799
                     /gene="MGMT"
                     /note="major polyA site"
     regulatory      1706..1711
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MGMT"
                     /note="hexamer: AATAAA"
     polyA_site      1737
                     /gene="MGMT"
     regulatory      1921..1926
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MGMT"
                     /note="hexamer: AAGAAA"
     polyA_site      1942
                     /gene="MGMT"
     regulatory      3115..3120
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MGMT"
                     /note="hexamer: AAGAAA"
     polyA_site      3131
                     /gene="MGMT"
     regulatory      4657..4662
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MGMT"
                     /note="hexamer: ATTAAA"
     polyA_site      4678
                     /gene="MGMT"
ORIGIN      
        1 aacgctttgc gtcccgacgc ccgcaggtcc tcgcggtgcg caccgtttgc gacttggtac
       61 ttggaaaaat ggacaaggat tgtgaaatga aacgcaccac actggacagc cctttgggga
      121 agctggagct gtctggttgt gagcagggtc tgcacgaaat aaagctcctg ggcaagggga
      181 cgtctgcagc tgatgccgtg gaggtcccag cccccgctgc ggttctcgga ggtccggagc
      241 ccctgatgca gtgcacagcc tggctgaatg cctatttcca ccagcccgag gctatcgaag
      301 agttccccgt gccggctctt caccatcccg ttttccagca agagtcgttc accagacagg
      361 tgttatggaa gctgctgaag gttgtgaaat tcggagaagt gatttcttac cagcaattag
      421 cagccctggc aggcaacccc aaagccgcgc gagcagtggg aggagcaatg agaggcaatc
      481 ctgtccccat cctcatcccg tgccacagag tggtctgcag cagcggagcc gtgggcaact
      541 actccggagg actggccgtg aaggaatggc ttctggccca tgaaggccac cggttgggga
      601 agccaggctt gggagggagc tcaggtctgg caggggcctg gctcaaggga gcgggagcta
      661 cctcgggctc cccgcctgct ggccgaaact gagtatgtgc agtaggatgg atgtttgagc
      721 gacacacacg tgtaacactg catcggatgc ggggcgtgga ggcaccgctg tattaaagga
      781 agtggcagtg tcctgggaac aagcgtgtct gccctttctg tttccatatt ttacagcagg
      841 atgagttcag acgcccgcgg tcctgcacac atttgtttcc ttctctaacg ctgcccttgc
      901 tctatttttc atgtccatta aaacaggcca agtgagtgtg gaaggcctgg ctcatgttgg
      961 gccacagccc aggatggggc agtctggcac cctcaggcca cagacggctg ccatagccgc
     1021 tgtccagggc cagctaaggc ccatcccagg ccgtccacac tagaaagctg gccctgcccc
     1081 atccccacca tgcctccctt cctggctgtg tccatggctg tgatggcatt ctccactcag
     1141 cagttcctag catcccacac ccaggtctca ctgaaagaaa ggggaacagg ccatggcagt
     1201 cagtgcttac agaggttttc tagctttgtt tcctacctgc caaaaaggct aatgcaagat
     1261 gcatccactt atggtctgta tcaggtgaat agaaaataac catttgccaa gatttggaaa
     1321 gacagagagc tctctggaca cgggttcgat ggagcttgca cctctctgag agctgaagtc
     1381 aagtctcacc ctctctccat actccctggc ctagtgtgct ctgggcagca ggtaggaagg
     1441 gacagggacc tctcatctca agggctgccc caaagggccc tcagggacca tgggcctgtt
     1501 aggaccccag caccccagtg tcgatcctgg aagtcaaagg tcacgactgt ggggggccag
     1561 ctcatgtcac tgatggcagc aggcagggtt tccagcatgg gcggtgcgct gctgtctgat
     1621 acttcattat tgtgttgtca tcctagctgt ataattaact atatccaaaa gccggaaggg
     1681 aaacctgtag ctctgcatat ggagaaataa aacagagcat atgatgtata gagaaaatga
     1741 actgcaccca gctgtgcact agagcgccat gttcttaccc agcattcctt gccacggtgt
     1801 gaaccacagc agggaagctc gcatggttct acacgtcacc gaggcctgga tgaaaatgtg
     1861 gcctcacgat gtgtatggtt gggacccgcc ttctatttca ttttatctta acaccaacga
     1921 aagaaaaccg atttcagacg tttttcgctg atttatgatt tattatatcc ctttctggca
     1981 tcagccaaaa tctcggtttt tcctatgaca tgaagtgatg tgactcttac cccgttgtct
     2041 taactcttgg tatttttgaa gcaggataag tcacacagcg ggtcacgtag acacgtgctg
     2101 ttttgtggga caggccctgg gcctccttgc tcctggcagg cctcaggtgc cgcacgccgc
     2161 gtcaccgtca ggactcgcag gctgtctggt catttttgac gttgctgaag gtgagtggga
     2221 aaagctgggt gcactctgcc ccaaaggtgg tgccctgtgt cccccacaga tgatggccct
     2281 ccccagtgat ggccggtcac caggcacggc tttcccctct gcatgaacag aacagaagct
     2341 tctggctctc caaggcagca gcttggggcc tggtggcccg ggtgtgcgag ccgcgagtgc
     2401 tttccaacag agggcaccag agccgtgcgg tgtgctgtgg agaccccagc accacttccc
     2461 ctgctggagg atggatttga aggagggtgg ctgggcggca ccccgatggc tccctgtgct
     2521 ccctgagacc ctacaggccg ccctctgcag ccacacctgg accggcaggc atgcacgctg
     2581 caggcaggct gcctccgctg tttgggtccc atgaacgatg gaagcctccc agtgagatct
     2641 tcaggtctct catcaggcac aggctctgag ggagggtcct ggggccacat gactgcagcc
     2701 agcgagggcc gagcccccag aatccaggtc agctcctggt ggcaggggac ctgcccgtca
     2761 aagccgtcca aggtgagcca gcaaatccgt gtggcctggg agcacaggtg ggcctgctcg
     2821 gaccatgccc ttggtgcagt acaaaaccat gttctgcttc ctctccgagg gtttccgcgg
     2881 ccctgtcaga acaggcttga tagatgcccg gaggttccct ctgacagccg cagcagcagg
     2941 gctcaaaccg gcggggccgt gtaccgctcc aaggacaagc tctgccgagg ccgacatgaa
     3001 aagccagcac gcgggtcgcc tagagccgct ctgcctccaa gctgcagcgc cgttcgtgaa
     3061 aatacagagg gagagggaag gcacaaagaa atacaaaact attttccaaa taaaaagaaa
     3121 tgtcgaaaca agaaagctgt gttcttcagc cttggccctg ggtccccctc accctgtcgc
     3181 atttcccagc actgtgatgc tttgaaggcc gacaccgaga cccgccgtgc acgacagcca
     3241 cctcgcagcc actcagaccg gcggaccacg ctcccctgtt tccagagaga tgagagagtc
     3301 agaagtaata cttgtttttg cagaaccaca cttgtggcaa aataagttgc ctttggccac
     3361 gcaggagact gagttttgtg aggggttgtc cttctcccag tctctcttcc cgctgggaac
     3421 agaagtgtcc agtaaaccca cctgcattcc acgtgtcctg tggccgcctc cagtggtgag
     3481 tctgtgaggc cagagaagag aagctatgac cgtgcaaaca tgcatgttat ggtgttggct
     3541 gatgcggaat caggaagctt ggaggagctc ttgcatgagg aattgcagaa cttaggggca
     3601 tgaatttgca cttccagatg tgaaggttgc aggcaccggg cgttgcagag gaagtgggca
     3661 agctcacctt gtagagaact tacttggggt ttgtaatttg tatacacttc ttacccagca
     3721 gaaacagctt actgaacacc cctcgggtgg ctggatgatg tgctagcaac tgaaaccatc
     3781 tctgcgactt aagcttctct ggtgcgtcgc gccccacgtg cttctccaga atcccgtttg
     3841 gaggggccaa gcaagtccaa tatagatagg tttatactga agccatcagt tttgtttctt
     3901 acatcgtttg taaacagcag tattatcctg gaacttgttt cctacagaac tgtaagataa
     3961 ggataaaatc ccatccacct gaattgctga gaaacgtaag aggtggtgtg acccgctgga
     4021 gccctgtgga gtggcggact ctggggagta gctggtcagt gagattctcg cagcaatgtg
     4081 aggcatcctc ctcacagaaa tgcatttacg gatgttgctg tatcccctga cctggcctac
     4141 aaggacagaa cagccctggg ggccacgtcc cctcccggtc tcatctgccg cttgctcacc
     4201 ttggctgtcc atgcacccgt agctgtgacc atgggcggtg gcgccagctc ggacttcacc
     4261 ccgttggagc gggcaggatg tcacactgag ctaatgtgag attgttcatg aagctacaga
     4321 tcttagtgct acttgggctt ctcacagcac agaggaggat tctgaagtga gagataaatt
     4381 ggcttcatgt atgagcaagg gggaaagtgt tttattttac taggaagatt ttactgaaag
     4441 accaatcccg aaacggccct tgcttcggcc acagctgctg ggatgtcctc gggcctcccc
     4501 tgtttgtctg catgtcttct tgttgccatc ggggcagtgg agtccccgga aacagtccaa
     4561 ggccctgggg tgggggattt aaatttttgg cttccctcag acctcagacc gtgtgggttt
     4621 ttttttcttt ctttctttcc tgttcatggg catttgatta aaagtttgtg tttaaaga
//
