KMT2D
Template:PBB Histone-lysine N-methyltransferase 2D (KMT2D) previously known as myeloid/lymphoid or mixed-lineage leukemia protein 2 (MLL2) is an enzyme that in humans is encoded by the KMT2D gene.[1][2] The gene is located on chromosome 12.This is a Trithorax-group protein.
Nomenclature
This gene is also generally known as MLL4 in the literature. This nomenclature has caused much confusion in the data bases. Originally MLL2 was used to describe the sister gene of MLL1, which is also a trithorax-group histone methyltransferase.
The MLL1 gene was originally named MLL after myeloid/lymphoid or mixed-lineage leukemia cases. Its closest homologue is a very similar gene (not the gene described here), which is also called MLL2, but sometimes unfortunately called MLL4. The gene described here as MLL2 should properly be called MLL4 because along with its closely related homologue MLL3, it is closely related to a different Drosophila homologue of trithorax. The material included below refers to the trithorax group protein that is associated with MLL3 and a protein complex, not containing menin but including PTIP. It is listed as MLL2 but it should properly be called MLL4. It is now understood that its effect in lymphomagenesis is via the disruption of chromatin regulation.[3]
Clinical significance
Two thirds of a sample of 53 cases of Kabuki Syndrome have a loss-of-function mutation in the KMT2D gene.[4]
Mutations of this gene are common in various types of B-cell lymphoma [3] and are also associated with medulloblastoma [5] and pheochromocytoma.[6]
References
- ^ Prasad R, Zhadanov AB, Sedkov Y, Bullrich F, Druck T, Rallapalli R, Yano T, Alder H, Croce CM, Huebner K, Mazo A, Canaani E (Aug 1997). "Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax". Oncogene. 15 (5): 549–60. doi:10.1038/sj.onc.1201211. PMID 9247308.
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: CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: MLL2 myeloid/lymphoid or mixed-lineage leukemia 2".
- ^ a b Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJ, Connors JM, Hirst M, Gascoyne RD, Marra MA (August 2011). "Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma". Nature. 476 (7360): 298–303. doi:10.1038/nature10351. PMC 3210554. PMID 21796119.
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: CS1 maint: multiple names: authors list (link) - ^ Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J (September 2010). "Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome". Nat. Genet. 42 (9): 790–3. doi:10.1038/ng.646. PMC 2930028. PMID 20711175.
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: CS1 maint: multiple names: authors list (link) - ^ Jones DT, Jäger N, Kool M, Zichner T, Hutter B, Sultan M, Cho YJ, Pugh TJ, Hovestadt V, Stütz AM, Rausch T, Warnatz HJ, Ryzhova M, Bender S, Sturm D, Pleier S, Cin H, Pfaff E, Sieber L, Wittmann A, Remke M, Witt H, Hutter S, Tzaridis T, Weischenfeldt J, Raeder B, Avci M, Amstislavskiy V, Zapatka M, Weber UD, Wang Q, Lasitschka B, Bartholomae CC, Schmidt M, von Kalle C, Ast V, Lawerenz C, Eils J, Kabbe R, Benes V, van Sluis P, Koster J, Volckmann R, Shih D, Betts MJ, Russell RB, Coco S, Tonini GP, Schüller U, Hans V, Graf N, Kim YJ, Monoranu C, Roggendorf W, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, von Deimling A, Witt O, Maass E, Rössler J, Ebinger M, Schuhmann MU, Frühwald MC, Hasselblatt M, Jabado N, Rutkowski S, von Bueren AO, Williamson D, Clifford SC, McCabe MG, Collins VP, Wolf S, Wiemann S, Lehrach H, Brors B, Scheurlen W, Felsberg J, Reifenberger G, Northcott PA, Taylor MD, Meyerson M, Pomeroy SL, Yaspo ML, Korbel JO, Korshunov A, Eils R, Pfister SM, Lichter P (July 2012). "Dissecting the genomic complexity underlying medulloblastoma". Nature. 488 (7409): 100–5. doi:10.1038/nature11284. PMC 3662966. PMID 22832583.
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: CS1 maint: multiple names: authors list (link) - ^ Juhlin CC, Stenman A, Haglund F, Clark VE, Brown TC, Baranoski J, Bilguvar K, Goh G, Welander J, Svahn F, Rubinstein JC, Caramuta S, Yasuno K, Günel M, Bäckdahl M, Gimm O, Söderkvist P, Prasad ML, Korah R, Lifton RP, Carling T (May 2015). "Whole-exome sequencing defines the mutational landscape of pheochromocytoma and identifies KMT2D as a recurrently mutated gene". Genes Chromosomes Cancer. 54 (9): 542–54. doi:10.1002/gcc.22267. PMID 26032282.
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: CS1 maint: multiple names: authors list (link)
Further reading
- Jiang JX, Deprez RH, Zwarthoff EC, Riegman PH (1996). "Characterization of four novel CAG repeat-containing cDNAs". Genomics. 30 (1): 91–3. doi:10.1006/geno.1995.0015. PMID 8595911.
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: CS1 maint: multiple names: authors list (link) - Imbert G, Saudou F, Yvert G, Devys D, Trottier Y, Garnier JM, Weber C, Mandel JL, Cancel G, Abbas N, Dürr A, Didierjean O, Stevanin G, Agid Y, Brice A (1996). "Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats". Nat. Genet. 14 (3): 285–91. doi:10.1038/ng1196-285. PMID 8896557.
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: CS1 maint: multiple names: authors list (link) - Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
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: CS1 maint: multiple names: authors list (link) - Goo YH, Sohn YC, Kim DH, Kim SW, Kang MJ, Jung DJ, Kwak E, Barlev NA, Berger SL, Chow VT, Roeder RG, Azorsa DO, Meltzer PS, Suh PG, Song EJ, Lee KJ, Lee YC, Lee JW (2003). "Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins". Mol. Cell. Biol. 23 (1): 140–9. doi:10.1128/MCB.23.1.140-149.2003. PMC 140670. PMID 12482968.
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: CS1 maint: multiple names: authors list (link) - Hughes CM, Rozenblatt-Rosen O, Milne TA, Copeland TD, Levine SS, Lee JC, Hayes DN, Shanmugam KS, Bhattacharjee A, Biondi CA, Kay GF, Hayward NK, Hess JL, Meyerson M (2004). "Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus". Mol. Cell. 13 (4): 587–97. doi:10.1016/S1097-2765(04)00081-4. PMID 14992727.
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: CS1 maint: multiple names: authors list (link) - Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (2004). "Functional proteomics mapping of a human signaling pathway". Genome Res. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
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: CS1 maint: multiple names: authors list (link) - Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
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: CS1 maint: multiple names: authors list (link) - Mo R, Rao SM, Zhu YJ (2006). "Identification of the MLL2 complex as a coactivator for estrogen receptor alpha". J. Biol. Chem. 281 (23): 15714–20. doi:10.1074/jbc.M513245200. PMID 16603732.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
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: CS1 maint: multiple names: authors list (link) - Issaeva I, Zonis Y, Rozovskaia T, Orlovsky K, Croce CM, Nakamura T, Mazo A, Eisenbach L, Canaani E (2007). "Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth". Mol. Cell. Biol. 27 (5): 1889–903. doi:10.1128/MCB.01506-06. PMC 1820476. PMID 17178841.
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: CS1 maint: multiple names: authors list (link)
External links
- GeneReviews/NCBI/NIH/UW entry on Kabuki syndrome, Kabuki Make-Up Syndrome, Niikawa-Kuroki Syndrome
- MLL2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.