KMT5B explained

Histone-lysine N-methyltransferase KMT5B is an enzyme that in humans is encoded by the KMT5B gene.^{[1] [2] [3]} The enzyme along with WHSC1 is responsible for dimethylation of lysine 20 on histone H4 in mouse and humans.^{[4] [5]}

This gene encodes a protein that contains a SET domain. SET domains appear to be protein-protein interaction domains that mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). Two alternatively spliced transcript variants have been found for this gene.

Role in pathology

Mutations of the KMT5B gene cause autosomal dominant intellectual developmental disorder 51, a condition first described in 2017 by Stessman et al.^[6]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Tryndyak VP, Kovalchuk O, Pogribny IP . Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins . Cancer Biol. Ther. . 5 . 1 . 65–70 . 2006 . 16322686 . 10.4161/cbt.5.1.2288 . 12268423 .
• Ewing RM, Chu P, Elisma F, etal . Large-scale mapping of human protein–protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 .

Notes and References

1. Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W . Identification of Novel Human Genes Evolutionarily Conserved in Caenorhabditis elegans by Comparative Proteomics . Genome Res . 10 . 5 . 703–13 . Aug 2000 . 10810093 . 310876 . 10.1101/gr.10.5.703 .
2. Twells RC, Metzker ML, Brown SD, Cox R, Garey C, Hammond H, Hey PJ, Levy E, Nakagawa Y, Philips MS, Todd JA, Hess JF . The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13 . Genomics . 72 . 3 . 231–42 . Jun 2001 . 11401438 . 10.1006/geno.2000.6492 .
3. Web site: KMT5B lysine methyltransferase 5B [Homo sapiens (human) ]].
4. 18676810 . 10.1101/gad.476008 . 22 . A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse . 2492754 . 2008 . Genes Dev. . 2048–61 . Schotta G, Sengupta R, Kubicek S, Malin S, Kauer M, Callén E, Celeste A, Pagani M, Opravil S, De La Rosa-Velazquez IA, Espejo A, Bedford MT, Nussenzweig A, Busslinger M, Jenuwein T. 15 .
5. 21293379 . 10.1038/nature09658 . 470 . MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites . 3064261 . 2011 . Nature . 124–8 . Pei H, Zhang L, Luo K, Qin Y, Chesi M, Fei F, Bergsagel PL, Wang L, You Z, Lou Z. 7332 . 2011Natur.470..124P .
6. Stessman HA, Xiong B, Coe BP, Wang T, Hoekzema K, Fenckova M, Kvarnung M, Gerdts J, Trinh S, Cosemans N, Vives L, Lin J, Turner TN, Santen G, Ruivenkamp C, Kriek M, van Haeringen A, Aten E, Friend K, Liebelt J, Barnett C, Haan E, Shaw M, Gecz J, Anderlid BM, Nordgren A, Lindstrand A, Schwartz C, Kooy RF, Vandeweyer G, Helsmoortel C, Romano C, Alberti A, Vinci M, Avola E, Giusto S, Courchesne E, Pramparo T, Pierce K, Nalabolu S, Amaral DG, Scheffer IE, Delatycki MB, Lockhart PJ, Hormozdiari F, Harich B, Castells-Nobau A, Xia K, Peeters H, Nordenskjöld M, Schenck A, Bernier RA, Eichler EE . Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases . Nature Genetics . 49 . 4 . 515–526 . April 2017 . 28191889 . 5374041 . 10.1038/ng.3792 .