DNMT3A

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DNA (cytosine-5-)-methyltransferase 3 alpha
Protein DNMT3A PDB 2QRV.png
Rendering based on PDB 2QRV.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DNMT3A ; DNMT3A2; M.HsaIIIA
External IDs OMIM602769 MGI1261827 HomoloGene7294 ChEMBL: 1992 GeneCards: DNMT3A Gene
EC number 2.1.1.37
RNA expression pattern
PBB GE DNMT3A 218457 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1788 13435
Ensembl ENSG00000119772 ENSMUSG00000020661
UniProt Q9Y6K1 O88508
RefSeq (mRNA) NM_022552 NM_001271753
RefSeq (protein) NP_072046 NP_001258682
Location (UCSC) Chr 2:
25.46 – 25.57 Mb
Chr 12:
3.81 – 3.91 Mb
PubMed search [1] [2]

DNA (cytosine-5)-methyltransferase 3A is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.[1][2]

Function[edit]

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than the maintenance of existing methylated sites. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. Alternative splicing results in multiple transcript variants encoding different isoforms.[3]


Clinical relevance[edit]

The study of this gene in mice has shown its reduced expression in ageing animals causes cognitive long-term memory decline.[4]

Interactions[edit]

DNMT3A has been shown to interact with:

References[edit]

  1. ^ Okano M, Xie S, Li E (July 1998). "Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases". Nat Genet 19 (3): 219–20. doi:10.1038/890. PMID 9662389. 
  2. ^ Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E (September 1999). "Cloning, expression and chromosome locations of the human DNMT3 gene family". Gene 236 (1): 87–95. doi:10.1016/S0378-1119(99)00252-8. PMID 10433969. 
  3. ^ "Entrez Gene: DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha". 
  4. ^ Oliveira AM, Hemstedt TJ, Bading H (2012). "Rescue of aging-associated decline in Dnmt3a2 expression restores cognitive abilities". Nat. Neurosci. 15 (8): 1111–3. doi:10.1038/nn.3151. PMID 22751036. 
  5. ^ a b Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (August 2002). "Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases". EMBO J. 21 (15): 4183–95. PMC 126147. PMID 12145218. 
  6. ^ a b c d Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD. "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription". Nucleic Acids Res. 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048. 
  7. ^ Lehnertz B, Ueda Y, Derijck AA, Braunschweig U, Perez-Burgos L, Kubicek S, Chen T, Li E, Jenuwein T, Peters AH (July 2003). "Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin". Curr. Biol. 13 (14): 1192–200. PMID 12867029. 
  8. ^ a b Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T (May 2001). "Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription". EMBO J. 20 (10): 2536–44. doi:10.1093/emboj/20.10.2536. PMC 125250. PMID 11350943. 
  9. ^ Brenner C, Deplus R, Didelot C, Loriot A, Viré E, De Smet C, Gutierrez A, Danovi D, Bernard D, Boon T, Pelicci PG, Amati B, Kouzarides T, de Launoit Y, Di Croce L, Fuks F (January 2005). "Myc represses transcription through recruitment of DNA methyltransferase corepressor". EMBO J. 24 (2): 336–46. doi:10.1038/sj.emboj.7600509. PMC 545804. PMID 15616584. 
  10. ^ Fuks F, Hurd PJ, Deplus R, Kouzarides T (May 2003). "The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase". Nucleic Acids Res. 31 (9): 2305–12. PMC 154218. PMID 12711675. 

Further reading[edit]