LOCUS       NM_001276270            2394 bp    mRNA    linear   PRI 23-APR-2024
DEFINITION  Homo sapiens methyl-CpG binding domain 4, DNA glycosylase (MBD4),
            transcript variant 2, mRNA.
ACCESSION   NM_001276270
VERSION     NM_001276270.2
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 2394)
  AUTHORS   Villy,M.C., Le Ven,A., Le Mentec,M., Masliah-Planchon,J., Houy,A.,
            Bieche,I., Vacher,S., Vincent-Salomon,A., Dubois d'Enghien,C.,
            Schwartz,M., Piperno-Neumann,S., Matet,A., Malaise,D., Bubien,V.,
            Lortholary,A., Ait Omar,A., Cavaille,M., Stoppa-Lyonnet,D.,
            Cassoux,N., Stern,M.H., Rodrigues,M., Golmard,L. and Colas,C.
  TITLE     Familial uveal melanoma and other tumors in 25 families with
            monoallelic germline MBD4 variants
  JOURNAL   J Natl Cancer Inst 116 (4), 580-587 (2024)
   PUBMED   38060262
  REMARK    GeneRIF: Familial uveal melanoma and other tumors in 25 families
            with monoallelic germline MBD4 variants.
REFERENCE   2  (bases 1 to 2394)
  AUTHORS   Papin,C., Ibrahim,A., Sabir,J.S.M., Le Gras,S., Stoll,I.,
            Albiheyri,R.S., Zari,A.T., Bahieldin,A., Bellacosa,A., Bronner,C.
            and Hamiche,A.
  TITLE     MBD4 loss results in global reactivation of promoters and
            retroelements with low methylated CpG density
  JOURNAL   J Exp Clin Cancer Res 42 (1), 301 (2023)
   PUBMED   37957685
  REMARK    GeneRIF: MBD4 loss results in global reactivation of promoters and
            retroelements with low methylated CpG density.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2394)
  AUTHORS   Saint-Ghislain,M., Derrien,A.C., Geoffrois,L., Gastaud,L.,
            Lesimple,T., Negrier,S., Penel,N., Kurtz,J.E., Le Corre,Y.,
            Dutriaux,C., Gardrat,S., Barnhill,R., Matet,A., Cassoux,N.,
            Houy,A., Ramtohul,T., Servois,V., Mariani,P., Piperno-Neumann,S.,
            Stern,M.H. and Rodrigues,M.
  TITLE     MBD4 deficiency is predictive of response to immune checkpoint
            inhibitors in metastatic uveal melanoma patients
  JOURNAL   Eur J Cancer 173, 105-112 (2022)
   PUBMED   35863105
  REMARK    GeneRIF: MBD4 deficiency is predictive of response to immune
            checkpoint inhibitors in metastatic uveal melanoma patients.
REFERENCE   4  (bases 1 to 2394)
  AUTHORS   Pidugu,L.S., Bright,H., Lin,W.J., Majumdar,C., Van Ostrand,R.P.,
            David,S.S., Pozharski,E. and Drohat,A.C.
  TITLE     Structural Insights into the Mechanism of Base Excision by MBD4
  JOURNAL   J Mol Biol 433 (15), 167097 (2021)
   PUBMED   34107280
  REMARK    GeneRIF: Structural Insights into the Mechanism of Base Excision by
            MBD4.
REFERENCE   5  (bases 1 to 2394)
  AUTHORS   Alekseeva,I.V., Bakman,A.S., Iakovlev,D.A., Kuznetsov,N.A. and
            Fedorova,O.S.
  TITLE     [Comparative Analysis of the Activity of the Polymorphic Variants
            of Human Uracil-DNA-Glycosylases SMUG1 and MBD4]
  JOURNAL   Mol Biol (Mosk) 55 (2), 277-288 (2021)
   PUBMED   33871441
  REMARK    GeneRIF: [Comparative Analysis of the Activity of the Polymorphic
            Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4].
REFERENCE   6  (bases 1 to 2394)
  AUTHORS   Hendrich,B., Hardeland,U., Ng,H.H., Jiricny,J. and Bird,A.
  TITLE     The thymine glycosylase MBD4 can bind to the product of deamination
            at methylated CpG sites
  JOURNAL   Nature 401 (6750), 301-304 (1999)
   PUBMED   10499592
  REMARK    Erratum:[Nature 2000 Mar 30;404(6777):525]
REFERENCE   7  (bases 1 to 2394)
  AUTHORS   Hendrich,B., Abbott,C., McQueen,H., Chambers,D., Cross,S. and
            Bird,A.
  TITLE     Genomic structure and chromosomal mapping of the murine and human
            Mbd1, Mbd2, Mbd3, and Mbd4 genes
  JOURNAL   Mamm Genome 10 (9), 906-912 (1999)
   PUBMED   10441743
REFERENCE   8  (bases 1 to 2394)
  AUTHORS   Bellacosa,A., Cicchillitti,L., Schepis,F., Riccio,A., Yeung,A.T.,
            Matsumoto,Y., Golemis,E.A., Genuardi,M. and Neri,G.
  TITLE     MED1, a novel human methyl-CpG-binding endonuclease, interacts with
            DNA mismatch repair protein MLH1
  JOURNAL   Proc Natl Acad Sci U S A 96 (7), 3969-3974 (1999)
   PUBMED   10097147
REFERENCE   9  (bases 1 to 2394)
  AUTHORS   Boland,C.R., Thibodeau,S.N., Hamilton,S.R., Sidransky,D.,
            Eshleman,J.R., Burt,R.W., Meltzer,S.J., Rodriguez-Bigas,M.A.,
            Fodde,R., Ranzani,G.N. and Srivastava,S.
  TITLE     A National Cancer Institute Workshop on Microsatellite Instability
            for cancer detection and familial predisposition: development of
            international criteria for the determination of microsatellite
            instability in colorectal cancer
  JOURNAL   Cancer Res 58 (22), 5248-5257 (1998)
   PUBMED   9823339
  REMARK    Review article
REFERENCE   10 (bases 1 to 2394)
  AUTHORS   Hendrich,B. and Bird,A.
  TITLE     Identification and characterization of a family of mammalian
            methyl-CpG binding proteins
  JOURNAL   Mol Cell Biol 18 (11), 6538-6547 (1998)
   PUBMED   9774669
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BP370521.1, BC011752.2 and
            DB568237.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_001276270.1.
            
            Summary: The protein encoded by this gene is a member of a family
            of nuclear proteins related by the presence of a methyl-CpG binding
            domain (MBD). These proteins are capable of binding specifically to
            methylated DNA, and some members can also repress transcription
            from methylated gene promoters. This protein contains an MBD domain
            at the N-terminus that functions both in binding to methylated DNA
            and in protein interactions and a C-terminal mismatch-specific
            glycosylase domain that is involved in DNA repair. Alternatively
            spliced transcript variants encoding multiple isoforms have been
            observed for this gene. [provided by RefSeq, Jan 2013].
            
            Transcript Variant: This variant (2) uses an alternate in-frame
            splice site in the 5' coding region, compared to variant 1. This
            results in a shorter protein (isoform 2), compared to isoform 1.
            
            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 :: BC011752.2, CR450305.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000429544.7/ ENSP00000394080.2
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-72                BP370521.1         233-304
            73-2064             BC011752.2         1-1992
            2065-2394           DB568237.1         153-482
FEATURES             Location/Qualifiers
     source          1..2394
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q21.3"
     gene            1..2394
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /note="methyl-CpG binding domain 4, DNA glycosylase"
                     /db_xref="GeneID:8930"
                     /db_xref="HGNC:HGNC:6919"
                     /db_xref="MIM:603574"
     exon            1..219
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     CDS             116..1840
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /note="isoform 2 is encoded by transcript variant 2;
                     3,N(4)-ethenocytosine glycosylase; G/T mismatch
                     glycosylase; G/U mismatch glycosylase; methyl-CpG binding
                     domain protein 4; G/5-fluorouracil mismatch glycosylase
                     with biphasic kinetics; putative methyl-CpG binding
                     protein; methyl-CpG-binding protein MBD4;
                     methyl-CpG-binding endonuclease 1; mismatch-specific DNA
                     N-glycosylase"
                     /codon_start=1
                     /product="methyl-CpG-binding domain protein 4 isoform 2"
                     /protein_id="NP_001263199.1"
                     /db_xref="CCDS:CCDS63768.1"
                     /db_xref="GeneID:8930"
                     /db_xref="HGNC:HGNC:6919"
                     /db_xref="MIM:603574"
                     /translation="MGTTGLESLSLGDRGAAPTVTSSERLVPDPPNDLRKEDVAMELE
                     RVGEDEEQMMIKRSSECNPLLQEPIASAQFGATAGTECRKSVPCGWERVVKQRLFGKT
                     AGRFDVYFISPQGLKFRSKSSLANYLHKNGETSLKPEDFDFTVLSKRGIKSRYKDCSM
                     AALTSHLQNQSNNSNWNLRTRSKCKKDVFMPPSSSSELQESRGLSNFTSTHLLLKEDE
                     GVDDVNFRKVRKPKGKVTILKGIPIKKTKKGCRKSCSGFVQSDSKRESVCNKADAESE
                     PVAQKSQLDRTVCISDAGACGETLSVTSEENSLVKKKERSLSSGSNFCSEQKTSGIIN
                     KFCSAKDSEHNEKYEDTFLESEEIGTKVEVVERKEHLHTDILKRGSEMDNNCSPTRKD
                     FTEDTIPRTQIERRKTSLYFSSKYNKEALSPPRRKAFKKWTPPRSPFNLVQETLFHDP
                     WKLLIATIFLNRTSGKMAIPVLWKFLEKYPSAEVARTADWRDVSELLKPLGLYDLRAK
                     TIVKFSDEYLTKQWKYPIELHGIGKYGNDSYRIFCVNEWKQVHPEDHKLNKYHDWLWE
                     NHEKLSLS"
     exon            220..450
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     exon            451..1298
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1299..1373
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1374..1508
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1509..1658
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1659..1762
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     exon            1763..2394
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2370..2375
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /note="hexamer: AATAAA"
     polyA_site      2394
                     /gene="MBD4"
                     /gene_synonym="MED1; TPDS2; UVM1"
                     /note="major polyA site"
ORIGIN      
        1 attcagacct cggttgcagc ccggtgccgt gagctgaaga ggtttcacat cttactccgc
       61 cccacaccct gggcgttgcg gcgctgggct cgttgctgca gccggaccct gctcgatggg
      121 cacgactggg ctggagagtc tgagtctggg ggaccgcgga gctgccccca ccgtcacctc
      181 tagtgagcgc ctagtcccag acccgccgaa tgacctccgc aaagaagatg ttgctatgga
      241 attggaaaga gtgggagaag atgaggaaca aatgatgata aaaagaagca gtgaatgtaa
      301 tcccttgcta caagaaccca tcgcttctgc tcagtttggt gctactgcag gaacagaatg
      361 ccgtaagtct gtcccatgtg gatgggaaag agttgtgaag caaaggttat ttgggaagac
      421 agcaggaaga tttgatgtgt actttatcag cccacaagga ctgaagttca gatccaaaag
      481 ttcacttgct aattatcttc acaaaaatgg agagacttct cttaagccag aagattttga
      541 ttttactgta ctttctaaaa ggggtatcaa gtcaagatat aaagactgca gcatggcagc
      601 cctgacatcc catctacaaa accaaagtaa caattcaaac tggaacctca ggacccgaag
      661 caagtgcaaa aaggatgtgt ttatgccgcc aagtagtagt tcagagttgc aggagagcag
      721 aggactctct aactttactt ccactcattt gcttttgaaa gaagatgagg gtgttgatga
      781 tgttaacttc agaaaggtta gaaagcccaa aggaaaggtg actattttga aaggaatccc
      841 aattaagaaa actaaaaaag gatgtaggaa gagctgttca ggttttgttc aaagtgatag
      901 caaaagagaa tctgtgtgta ataaagcaga tgctgaaagt gaacctgttg cacaaaaaag
      961 tcagcttgat agaactgtct gcatttctga tgctggagca tgtggtgaga ccctcagtgt
     1021 gaccagtgaa gaaaacagcc ttgtaaaaaa aaaagaaaga tcattgagtt caggatcaaa
     1081 tttttgttct gaacaaaaaa cttctggcat cataaacaaa ttttgttcag ccaaagactc
     1141 agaacacaac gagaagtatg aggatacctt tttagaatct gaagaaatcg gaacaaaagt
     1201 agaagttgtg gaaaggaaag aacatttgca tactgacatt ttaaaacgtg gctctgaaat
     1261 ggacaacaac tgctcaccaa ccaggaaaga cttcactgaa gataccatcc cacgaacaca
     1321 gatagaaaga aggaaaacaa gcctgtattt ttccagcaaa tataacaaag aagctcttag
     1381 ccccccacga cgtaaagcct ttaagaaatg gacacctcct cggtcacctt ttaatctcgt
     1441 tcaagaaaca ctttttcatg atccatggaa gcttctcatc gctactatat ttctcaatcg
     1501 gacctcaggc aaaatggcaa tacctgtgct ttggaagttt ctggagaagt atccttcagc
     1561 tgaggtagca agaaccgcag actggagaga tgtgtcagaa cttcttaaac ctcttggtct
     1621 ctacgatctt cgggcaaaaa ccattgtcaa gttctcagat gaatacctga caaagcagtg
     1681 gaagtatcca attgagcttc atgggattgg taaatatggc aacgactctt accgaatttt
     1741 ttgtgtcaat gagtggaagc aggtgcaccc tgaagaccac aaattaaata aatatcatga
     1801 ctggctttgg gaaaatcatg aaaaattaag tctatcttaa actctgcagc tttcaagctc
     1861 atctgttatg catagctttg cacttcaaaa aagcttaatt aagtacaacc aaccaccttt
     1921 ccagccatag agattttaat tagcccaact agaagcctag tgtgtgtgct ttcttaatgt
     1981 gtgtgccaat ggtggatctt tgctactgaa tgtgtttgaa catgttttga gattttttta
     2041 aaataaatta ttatttgaca acaatccaaa aaaaatacgg cttttccaat gatgaaatat
     2101 aatcagaaga tgaaaaatag ttctaaacta tcaataatac aaagcaaatt tctatcagcc
     2161 ttgctaaagc taggggccca ctaaatattt ttatcggcta ggcgtggtgg tgcatgcctg
     2221 taatctcgga aggctgaggc aggaggatca tttgagctca tgagggccca ggaggtcaag
     2281 gcttcagtga gccatgatca tgccactgca ctccagtctg gatgacagag agagaccctg
     2341 tctcaaaaaa tatatattta aaaaataaaa ataaaagctg accccaaaga caaa
//
