DNA (cytosine-5)-methyltransferase 3B

Details

Name
DNA (cytosine-5)-methyltransferase 3B
Synonyms
  • 2.1.1.37
  • DNA methyltransferase HsaIIIB
  • DNA MTase HsaIIIB
  • Dnmt3b
  • M.HsaIIIB
Gene Name
DNMT3B
UniProtKB Entry
Q9UBC3Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0052502|DNA (cytosine-5)-methyltransferase 3B
MKGDTRHLNGEEDAGGREDSILVNGACSDQSSDSPPILEAIRTPEIRGRRSSSRLSKREV
SSLLSYTQDLTGDGDGEDGDGSDTPVMPKLFRETRTRSESPAVRTRNNNSVSSRERHRPS
PRSTRGRQGRNHVDESPVEFPATRSLRRRATASAGTPWPSPPSSYLTIDLTDDTEDTHGT
PQSSSTPYARLAQDSQQGGMESPQVEADSGDGDSSEYQDGKEFGIGDLVWGKIKGFSWWP
AMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRK
AMYHALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGFKPTGIEGLKPNNTQPVVNKS
KVRRAGSRKLESRKYENKTRRRTADDSATSDYCPAPKRLKTNCYNNGKDRGDEDQSREQM
ASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTV
CCEGRELLLCSNTSCCRCFCVECLEVLVGTGTAAEAKLQEPWSCYMCLPQRCHGVLRRRK
DWNVRLQAFFTSDTGLEYEAPKLYPAIPAARRRPIRVLSLFDGIATGYLVLKELGIKVGK
YVASEVCEESIAVGTVKHEGNIKYVNDVRNITKKNIEEWGPFDLVIGGSPCNDLSNVNPA
RKGLYEGTGRLFFEFYHLLNYSRPKEGDDRPFFWMFENVVAMKVGDKRDISRFLECNPVM
IDAIKVSAAHRARYFWGNLPGMNRPVIASKNDKLELQDCLEYNRIAKLKKVQTITTKSNS
IKQGKNQLFPVVMNGKEDVLWCTELERIFGFPVHYTDVSNMGRGARQKLLGRSWSVPVIR
HLFAPLKDYFACE
Number of residues
853
Molecular Weight
95750.18
Theoretical pI
Not Available
GO Classification
Functions
DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates
Processes
methylation
Components
catalytic complex
General Function
Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Functions as a transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells (PubMed:27153398)
Specific Function
Dna (cytosine-5-)-methyltransferase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0052503|DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
ATGAAGGGAGACACCAGGCATCTCAATGGAGAGGAGGACGCCGGCGGGAGGGAAGACTCG
ATCCTCGTCAACGGGGCCTGCAGCGACCAGTCCTCCGACTCGCCCCCAATCCTGGAGGCT
ATCCGCACCCCGGAGATCAGAGGCCGAAGATCAAGCTCGCGACTCTCCAAGAGGGAGGTG
TCCAGTCTGCTAAGCTACACACAGGACTTGACAGGCGATGGCGACGGGGAAGATGGGGAT
GGCTCTGACACCCCAGTCATGCCAAAGCTCTTCCGGGAAACCAGGACTCGTTCAGAAAGC
CCAGCTGTCCGAACTCGAAATAACAACAGTGTCTCCAGCCGGGAGAGGCACAGGCCTTCC
CCACGTTCCACCCGAGGCCGGCAGGGCCGCAACCATGTGGACGAGTCCCCCGTGGAGTTC
CCGGCTACCAGGTCCCTGAGACGGCGGGCAACAGCATCGGCAGGAACGCCATGGCCGTCC
CCTCCCAGCTCTTACCTTACCATCGACCTCACAGACGACACAGAGGACACACATGGGACG
CCCCAGAGCAGCAGTACCCCCTACGCCCGCCTAGCCCAGGACAGCCAGCAGGGGGGCATG
GAGTCCCCGCAGGTGGAGGCAGACAGTGGAGATGGAGACAGTTCAGAGTATCAGGATGGG
AAGGAGTTTGGAATAGGGGACCTCGTGTGGGGAAAGATCAAGGGCTTCTCCTGGTGGCCC
GCCATGGTGGTGTCTTGGAAGGCCACCTCCAAGCGACAGGCTATGTCTGGCATGCGGTGG
GTCCAGTGGTTTGGCGATGGCAAGTTCTCCGAGGTCTCTGCAGACAAACTGGTGGCACTG
GGGCTGTTCAGCCAGCACTTTAATTTGGCCACCTTCAATAAGCTCGTCTCCTATCGAAAA
GCCATGTACCATGCTCTGGAGAAAGCTAGGGTGCGAGCTGGCAAGACCTTCCCCAGCAGC
CCTGGAGACTCATTGGAGGACCAGCTGAAGCCCATGTTGGAGTGGGCCCACGGGGGCTTC
AAGCCCACTGGGATCGAGGGCCTCAAACCCAACAACACGCAACCAGTGGTTAATAAGTCG
AAGGTGCGTCGTGCAGGCAGTAGGAAATTAGAATCAAGGAAATACGAGAACAAGACTCGA
AGACGCACAGCTGACGACTCAGCCACCTCTGACTACTGCCCCGCACCCAAGCGCCTCAAG
ACAAATTGCTATAACAACGGCAAAGACCGAGGGGATGAAGATCAGAGCCGAGAACAAATG
GCTTCAGATGTTGCCAACAACAAGAGCAGCCTGGAAGATGGCTGTTTGTCTTGTGGCAGG
AAAAACCCCGTGTCCTTCCACCCTCTCTTTGAGGGGGGGCTCTGTCAGACATGCCGGGAT
CGCTTCCTTGAGCTGTTTTACATGTATGATGACGATGGCTATCAGTCTTACTGCACTGTG
TGCTGCGAGGGCCGAGAGCTGCTGCTTTGCAGCAACACGAGCTGCTGCCGGTGTTTCTGT
GTGGAGTGCCTGGAGGTGCTGGTGGGCACAGGCACAGCGGCCGAGGCCAAGCTTCAGGAG
CCCTGGAGCTGTTACATGTGTCTCCCGCAGCGCTGTCATGGCGTCCTGCGGCGCCGGAAG
GACTGGAACGTGCGCCTGCAGGCCTTCTTCACCAGTGACACGGGGCTTGAATATGAAGCC
CCCAAGCTGTACCCTGCCATTCCCGCAGCCCGAAGGCGGCCCATTCGAGTCCTGTCATTG
TTTGATGGCATCGCGACAGGCTACCTAGTCCTCAAAGAGTTGGGCATAAAGGTAGGAAAG
TACGTCGCTTCTGAAGTGTGTGAGGAGTCCATTGCTGTTGGAACCGTGAAGCACGAGGGG
AATATCAAATACGTGAACGACGTGAGGAACATCACAAAGAAAAATATTGAAGAATGGGGC
CCATTTGACTTGGTGATTGGCGGAAGCCCATGCAACGATCTCTCAAATGTGAATCCAGCC
AGGAAAGGCCTGTATGAGGGTACAGGCCGGCTCTTCTTCGAATTTTACCACCTGCTGAAT
TACTCACGCCCCAAGGAGGGTGATGACCGGCCGTTCTTCTGGATGTTTGAGAATGTTGTA
GCCATGAAGGTTGGCGACAAGAGGGACATCTCACGGTTCCTGGAGTGTAATCCAGTGATG
ATTGATGCCATCAAAGTTTCTGCTGCTCACAGGGCCCGATACTTCTGGGGCAACCTACCC
GGGATGAACAGGCCCGTGATAGCATCAAAGAATGATAAACTCGAGCTGCAGGACTGCTTG
GAATACAATAGGATAGCCAAGTTAAAGAAAGTACAGACAATAACCACCAAGTCGAACTCG
ATCAAACAGGGGAAAAACCAACTTTTCCCTGTTGTCATGAATGGCAAAGAAGATGTTTTG
TGGTGCACTGAGCTCGAAAGGATCTTTGGCTTTCCTGTGCACTACACAGACGTGTCCAAC
ATGGGCCGTGGTGCCCGCCAGAAGCTGCTGGGAAGGTCCTGGAGCGTGCCTGTCATCCGA
CACCTCTTCGCCCCTCTGAAGGACTACTTTGCATGTGAATAG
Chromosome Location
20
Locus
20q11.21
External Identifiers
ResourceLink
UniProtKB IDQ9UBC3
UniProtKB Entry NameDNM3B_HUMAN
GeneCard IDDNMT3B
HGNC IDHGNC:2979
PDB ID(s)3FLG, 3QKJ, 5CIU, 5NR3, 5NRR, 5NRS, 5NRV, 5NV0, 5NV2, 5NV7, 5NVO, 6KDA, 6KDB, 6KDL, 6KDP, 6KDT, 6PA7, 6R3E, 6U8P, 6U8V, 6U8W, 6U8X, 6U90, 6U91, 7O45, 7V0E, 7X9D, 8EIH, 8EII, 8EIJ, 8EIK
KEGG IDhsa:1789
NCBI Gene ID1789
General References
  1. Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E: Cloning, expression and chromosome locations of the human DNMT3 gene family. Gene. 1999 Aug 5;236(1):87-95. [Article]
  2. Xu GL, Bestor TH, Bourc'his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Pequignot E: Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature. 1999 Nov 11;402(6758):187-91. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [Article]
  5. Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA: The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res. 1999 Jun 1;27(11):2291-8. [Article]
  6. Kang ES, Park CW, Chung JH: Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1. Biochem Biophys Res Commun. 2001 Dec 14;289(4):862-8. [Article]
  7. Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S: Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J. 2002 Aug 1;21(15):4183-95. [Article]
  8. Li H, Rauch T, Chen ZX, Szabo PE, Riggs AD, Pfeifer GP: The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006 Jul 14;281(28):19489-500. Epub 2006 May 8. [Article]
  9. Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F: The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006 Feb 16;439(7078):871-4. Epub 2005 Dec 14. [Article]
  10. Kim SH, Park J, Choi MC, Kim HP, Park JH, Jung Y, Lee JH, Oh DY, Im SA, Bang YJ, Kim TY: Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression. Biochem Biophys Res Commun. 2007 Apr 6;355(2):318-23. Epub 2007 Feb 8. [Article]
  11. Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, Bergman Y, Simon I, Cedar H: Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat Genet. 2007 Feb;39(2):232-6. Epub 2006 Dec 31. [Article]
  12. Sun L, Huang L, Nguyen P, Bisht KS, Bar-Sela G, Ho AS, Bradbury CM, Yu W, Cui H, Lee S, Trepel JB, Feinberg AP, Gius D: DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer Res. 2008 Apr 15;68(8):2726-35. doi: 10.1158/0008-5472.CAN-07-6654. [Article]
  13. Kim SH, Park J, Choi MC, Park JH, Kim HP, Lee JH, Oh DY, Im SA, Bang YJ, Kim TY: DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription. Int J Biochem Cell Biol. 2008;40(11):2462-71. doi: 10.1016/j.biocel.2008.04.018. Epub 2008 May 18. [Article]
  14. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  15. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  16. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  17. Hendriks IA, Lyon D, Young C, Jensen LJ, Vertegaal AC, Nielsen ML: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat Struct Mol Biol. 2017 Mar;24(3):325-336. doi: 10.1038/nsmb.3366. Epub 2017 Jan 23. [Article]
  18. Wu H, Zeng H, Lam R, Tempel W, Amaya MF, Xu C, Dombrovski L, Qiu W, Wang Y, Min J: Structural and histone binding ability characterizations of human PWWP domains. PLoS One. 2011;6(6):e18919. doi: 10.1371/journal.pone.0018919. Epub 2011 Jun 20. [Article]
  19. Okano M, Bell DW, Haber DA, Li E: DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999 Oct 29;99(3):247-57. [Article]
  20. Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM: The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14412-7. [Article]
  21. Wijmenga C, Hansen RS, Gimelli G, Bjorck EJ, Davies EG, Valentine D, Belohradsky BH, van Dongen JJ, Smeets DF, van den Heuvel LP, Luyten JA, Strengman E, Weemaes C, Pearson PL: Genetic variation in ICF syndrome: evidence for genetic heterogeneity. Hum Mutat. 2000 Dec;16(6):509-17. [Article]
  22. Jiang YL, Rigolet M, Bourc'his D, Nigon F, Bokesoy I, Fryns JP, Hulten M, Jonveaux P, Maraschio P, Megarbane A, Moncla A, Viegas-Pequignot E: DNMT3B mutations and DNA methylation defect define two types of ICF syndrome. Hum Mutat. 2005 Jan;25(1):56-63. [Article]
  23. Kaya N, Al-Muhsen S, Al-Saud B, Al-Bakheet A, Colak D, Al-Ghonaium A, Al-Dhekri H, Al-Mousa H, Arnaout R, Al-Owain M, Iqbal M: ICF syndrome in Saudi Arabia: immunological, cytogenetic and molecular analysis. J Clin Immunol. 2011 Apr;31(2):245-52. doi: 10.1007/s10875-010-9488-0. Epub 2010 Dec 1. [Article]
  24. van den Boogaard ML, Lemmers RJLF, Balog J, Wohlgemuth M, Auranen M, Mitsuhashi S, van der Vliet PJ, Straasheijm KR, van den Akker RFP, Kriek M, Laurense-Bik MEY, Raz V, van Ostaijen-Ten Dam MM, Hansson KBM, van der Kooi EL, Kiuru-Enari S, Udd B, van Tol MJD, Nishino I, Tawil R, Tapscott SJ, van Engelen BGM, van der Maarel SM: Mutations in DNMT3B Modify Epigenetic Repression of the D4Z4 Repeat and the Penetrance of Facioscapulohumeral Dystrophy. Am J Hum Genet. 2016 May 5;98(5):1020-1029. doi: 10.1016/j.ajhg.2016.03.013. [Article]
  25. Rechavi E, Lev A, Eyal E, Barel O, Kol N, Barhom SF, Pode-Shakked B, Anikster Y, Somech R, Simon AJ: A Novel Mutation in a Critical Region for the Methyl Donor Binding in DNMT3B Causes Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome (ICF). J Clin Immunol. 2016 Nov;36(8):801-809. doi: 10.1007/s10875-016-0340-z. Epub 2016 Oct 12. [Article]

Associated Data

Bio-Entities
Bio-EntityType
DNA (cytosine-5)-methyltransferase 3B (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Decitabineapproved, investigationalunknowntargetinhibitorDetails
S-adenosyl-L-homocysteineexperimentalyestargetinhibitorDetails
Curcuminapproved, investigationalyestargetinhibitorDetails