Protein-coding gene in the species Homo sapiens
| DNMT3B |
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| Available structures |
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| PDB | Ortholog search: PDBe RCSB |
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| List of PDB id codes |
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3QKJ, 3FLG, 5CIU |
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| Identifiers |
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| Aliases | DNMT3B, ICF, ICF1, M.HsaIIIB, DNA (cytosine-5-)-methyltransferase 3 beta, DNA methyltransferase 3 beta, FSHD4 |
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| External IDs | OMIM: 602900; MGI: 1261819; HomoloGene: 56000; GeneCards: DNMT3B; OMA:DNMT3B - orthologs |
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| Gene location (Human) |
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 | | Chr. | Chromosome 20 (human)[1] |
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| | Band | 20q11.21 | Start | 32,762,385 bp[1] |
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| End | 32,809,356 bp[1] |
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| Gene location (Mouse) |
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 | | Chr. | Chromosome 2 (mouse)[2] |
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| | Band | 2|2 H1 | Start | 153,491,370 bp[2] |
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| End | 153,529,650 bp[2] |
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| RNA expression pattern |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - secondary oocyte
- hair follicle
- sperm
- embryo
- gonad
- testicle
- ganglionic eminence
- body of pancreas
- ventricular zone
- corpus epididymis
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| | Top expressed in | - epiblast
- primitive streak
- embryo
- pelvic part of vagina
- paramesonephric duct
- epithelium of vagina
- ejaculatory duct
- tail of embryo
- abdominal wall
- embryo
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| | More reference expression data |
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| BioGPS |  | | More reference expression data |
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| Gene ontology |
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| Molecular function | - methyltransferase activity
- transferase activity
- DNA binding
- transcription corepressor activity
- DNA-methyltransferase activity
- chromatin binding
- metal ion binding
- protein binding
- DNA (cytosine-5-)-methyltransferase activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- histone deacetylase binding
| | Cellular component | - cytoplasm
- intracellular membrane-bounded organelle
- nucleoplasm
- nucleus
| | Biological process | - response to ionizing radiation
- C-5 methylation of cytosine
- response to estradiol
- response to hypoxia
- cellular response to hyperoxia
- negative regulation of transcription by RNA polymerase II
- response to activity
- cellular response to dexamethasone stimulus
- response to vitamin A
- DNA methylation
- methylation
- positive regulation of gene expression
- negative regulation of gene expression, epigenetic
- positive regulation of histone H3-K4 methylation
- positive regulation of neuron differentiation
- negative regulation of histone H3-K9 methylation
- regulation of gene expression
- response to caffeine
- response to toxic substance
- response to cocaine
| | Sources:Amigo / QuickGO |
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| Orthologs |
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| Species | Human | Mouse |
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| Entrez | | |
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| Ensembl | | |
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| UniProt | | |
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| RefSeq (mRNA) | NM_001207055
NM_001207056
NM_006892
NM_175848
NM_175849
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NM_175850 |
| NM_001003960
NM_001003961
NM_001003963
NM_001122997
NM_001271744
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NM_001271745
NM_001271746
NM_001271747
NM_010068 |
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| RefSeq (protein) | NP_001193984
NP_001193985
NP_008823
NP_787044
NP_787045
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NP_787046 |
| NP_001003960
NP_001003961
NP_001003963
NP_001116469
NP_001258673
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NP_001258674
NP_001258675
NP_001258676
NP_034198 |
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| Location (UCSC) | Chr 20: 32.76 – 32.81 Mb | Chr 2: 153.49 – 153.53 Mb |
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| PubMed search | [3] | [4] |
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| Wikidata |
| View/Edit Human | View/Edit Mouse |
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DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene.[5] Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome.[6]
Function
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 which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined.[5]
Clinical significance
Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a result of defects in lymphocyte maturation resulting from aberrant DNA methylation caused by mutations in the DNMT3B gene.[6]
Variants of the gene can also contribute to nicotine dependency.[7]
Interactions
DNMT3B has been shown to interact with:
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000088305 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027478 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta".
- ^ a b Ehrlich M (October 2003). "The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease". Clinical Immunology. 109 (1): 17–28. doi:10.1016/S1521-6616(03)00201-8. PMID 14585272.
- ^ Hancock DB, Guo Y, Reginsson GW, Gaddis NC, Lutz SM, Sherva R, et al. (October 2017). "Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence". Molecular Psychiatry. 23 (9): 1911–1919. doi:10.1038/mp.2017.193. PMC 5882602. PMID 28972577.
- ^ a b c 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". Current Biology. 13 (14): 1192–200. Bibcode:2003CBio...13.1192L. doi:10.1016/s0960-9822(03)00432-9. PMID 12867029. S2CID 2320997.
- ^ 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". The EMBO Journal. 21 (15): 4183–95. doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
- ^ Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD (2004). "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 Research. 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048.
- ^ a b c Geiman TM, Sankpal UT, Robertson AK, Chen Y, Mazumdar M, Heale JT, Schmiesing JA, Kim W, Yokomori K, Zhao Y, Robertson KD (2004). "Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery". Nucleic Acids Research. 32 (9): 2716–29. doi:10.1093/nar/gkh589. PMC 419596. PMID 15148359.
- ^ a b Kang ES, Park CW, Chung JH (December 2001). "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochemical and Biophysical Research Communications. 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. PMID 11735126.
Further reading
- Wijmenga C, Hansen RS, Gimelli G, Björck EJ, Davies EG, Valentine D, Belohradsky BH, van Dongen JJ, Smeets DF, van den Heuvel LP, Luyten JA, Strengman E, Weemaes C, Pearson PL (December 2000). "Genetic variation in ICF syndrome: evidence for genetic heterogeneity". Human Mutation. 16 (6): 509–17. doi:10.1002/1098-1004(200012)16:6<509::AID-HUMU8>3.0.CO;2-V. PMID 11102980. S2CID 6746943.
- Okano M, Xie S, Li E (July 1998). "Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases". Nature Genetics. 19 (3): 219–20. doi:10.1038/890. PMID 9662389. S2CID 256263.
- Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (June 1999). "The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors". Nucleic Acids Research. 27 (11): 2291–8. doi:10.1093/nar/27.11.2291. PMC 148793. PMID 10325416.
- Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E (August 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.
- Okano M, Bell DW, Haber DA, Li E (October 1999). "DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development". Cell. 99 (3): 247–57. doi:10.1016/S0092-8674(00)81656-6. PMID 10555141. S2CID 15122892.
- Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM (December 1999). "The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome". Proceedings of the National Academy of Sciences of the United States of America. 96 (25): 14412–7. Bibcode:1999PNAS...9614412H. doi:10.1073/pnas.96.25.14412. PMC 24450. PMID 10588719.
- Xu GL, Bestor TH, Bourc'his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Péquignot E (November 1999). "Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene". Nature. 402 (6758): 187–91. Bibcode:1999Natur.402..187X. doi:10.1038/46052. PMID 10647011. S2CID 4338524.
- Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- 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". The EMBO Journal. 20 (10): 2536–44. doi:10.1093/emboj/20.10.2536. PMC 125250. PMID 11350943.
- Kang ES, Park CW, Chung JH (December 2001). "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochemical and Biophysical Research Communications. 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. PMID 11735126.
- Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B (April 2002). "DNMT1 and DNMT3b cooperate to silence genes in human cancer cells". Nature. 416 (6880): 552–6. Bibcode:2002Natur.416..552R. doi:10.1038/416552a. PMID 11932749. S2CID 4397868.
- Hata K, Okano M, Lei H, Li E (April 2002). "Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice". Development. 129 (8): 1983–93. doi:10.1242/dev.129.8.1983. PMID 11934864.
- Beaulieu N, Morin S, Chute IC, Robert MF, Nguyen H, MacLeod AR (August 2002). "An essential role for DNA methyltransferase DNMT3B in cancer cell survival". The Journal of Biological Chemistry. 277 (31): 28176–81. doi:10.1074/jbc.M204734200. PMID 12015329.
- Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S (July 2002). "Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis". Proceedings of the National Academy of Sciences of the United States of America. 99 (15): 10060–5. Bibcode:2002PNAS...9910060S. doi:10.1073/pnas.152121799. PMC 126624. PMID 12110732.
- 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". The EMBO Journal. 21 (15): 4183–95. doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
- Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, Fuks F (September 2002). "Dnmt3L is a transcriptional repressor that recruits histone deacetylase". Nucleic Acids Research. 30 (17): 3831–8. doi:10.1093/nar/gkf509. PMC 137431. PMID 12202768.
- Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q (September 2002). "A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer". Cancer Research. 62 (17): 4992–5. PMID 12208751.
- Shirohzu H, Kubota T, Kumazawa A, Sado T, Chijiwa T, Inagaki K, Suetake I, Tajima S, Wakui K, Miki Y, Hayashi M, Fukushima Y, Sasaki H (September 2002). "Three novel DNMT3B mutations in Japanese patients with ICF syndrome". American Journal of Medical Genetics. 112 (1): 31–7. doi:10.1002/ajmg.10658. PMID 12239717.
External links
1khc: Crystal Structure of the PWWP Domain of Mammalian DNA Methyltransferase Dnmt3b
