KMT2A

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"HRX" redirects here. For the bank holding, see Hypo Real Estate. For a language, the ISO 639-3 code of which is hrx, see Riograndenser Hunsrückisch German.
Lysine (K)-specific methyltransferase 2A
Protein MLL PDB 2j2s.png
PDB rendering based on 2j2s.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols KMT2A ; ALL-1; CXXC7; HRX; HTRX1; MLL; MLL/GAS7; MLL1; MLL1A; TET1-MLL; TRX1; WDSTS
External IDs OMIM159555 MGI96995 HomoloGene4338 ChEMBL: 1293299 GeneCards: KMT2A Gene
EC number 2.1.1.43
RNA expression pattern
PBB GE MLL 212080 at tn.png
PBB GE MLL 212076 at tn.png
PBB GE MLL 212078 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4297 214162
Ensembl ENSG00000118058 ENSMUSG00000002028
UniProt Q03164 P55200
RefSeq (mRNA) NM_001197104 NM_001081049
RefSeq (protein) NP_001184033 NP_001074518
Location (UCSC) Chr 11:
118.31 – 118.4 Mb
Chr 9:
44.8 – 44.88 Mb
PubMed search [1] [2]

Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the KMT2A gene (lysine (K)-specific methyltransferase 2A; synonyms MLL, ALL1). "MLL" stands for myeloid/lymphoid, or mixed-lineage, leukemia.[1]

MLL is a histone methyltransferase deemed a positive global regulator of gene transcription. This protein belongs to the group of histone-modifying enzymes comprising transactivation domain 9aaTAD[2] and is involved in the epigenetic maintenance of transcriptional memory.

Rearrangements of the MLL gene are associated with aggressive acute leukemias, both lymphoblastic and myeloid.[3] It also may participate in the process of GAD67 downregulation in schizophrenia.[4]

Clinical significance[edit]

Mutations in MLL cause Wiedemann-Steiner syndrome .[5]

Interactions[edit]

MLL (gene) has been shown to interact with:

References[edit]

  1. ^ Ziemin-van der Poel S, McCabe N, Gill H, Espinosa R, Patel Y, Harden A et al. (January 1992). "Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias". Proc Natl Acad Sci U S A 88 (23): 10735–9. doi:10.1073/pnas.88.23.10735. PMC 53005. PMID 1720549. 
  2. ^ Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics 89 (6): 756–68. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953. ; Piskacek M (November 2009). "Common Transactivation Motif 9aaTAD recruits multiple general co-activators TAF9, MED15, CBP and p300". Nature Precedings: Prepublication research and preliminary findings. doi:10.1038/npre.2009.3488.2. ; Piskacek M (November 2009). "9aaTADs mimic DNA to interact with a pseudo-DNA Binding Domain KIX of Med15 (Molecular Chameleons)". Nature Precedings: Prepublication research and preliminary findings. doi:10.1038/npre.2009.3939.1. ; Goto N, Zor T, Martinez-Yamout M, Dyson H, Wright P (November 2002). "Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain". J. Biol. Chem. 277 (45): 43168–74. doi:10.1074/jbc.M207660200. PMID 12205094. ; Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y et al. (December 1995). "Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12160–4. doi:10.1073/pnas.92.26.12160. PMC 40316. PMID 8618864. ; Ernst P, Wang J, Huang M, Goodman R, Korsmeyer S (April 2001). "MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein". Mol. Cell. Biol. 21 (7): 2249–58. doi:10.1128/MCB.21.7.2249-2258.2001. PMC 86859. PMID 11259575. 
  3. ^ Guenther M, Jenner R, Chevalier B, Nakamura T, Croce C, Canaani E et al. (June 2005). "Global and Hox-specific roles for the MLL1 methyltransferase". Proc. Natl. Acad. Sci. U.S.A. 102 (24): 8603–8. doi:10.1073/pnas.0503072102. PMC 1150839. PMID 15941828. 
  4. ^ Huang H, Matevossian A, Whittle C, Kim S, Schumacher A, Baker S et al. (October 2007). "Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters". J. Neurosci. 27 (42): 11254–62. doi:10.1523/JNEUROSCI.3272-07.2007. PMID 17942719. 
  5. ^ Mendelsohn B, Pronold M, Long R, Smaoui N, Slavotinek A (2014). "Advanced bone age in a girl with Wiedemann-Steiner syndrome and an exonic deletion in KMT2A (MLL)". American Journal of Medical Genetics Part A 164 (8): n/a. doi:10.1002/ajmg.a.36590. PMID 24818805. 
  6. ^ a b c d e Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero D, Kitabayashi I et al. (July 2004). "Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression". Mol. Cell. Biol. 24 (13): 5639–49. doi:10.1128/MCB.24.13.5639-5649.2004. PMC 480881. PMID 15199122. 
  7. ^ Goto N, Zor T, Martinez-Yamout M, Dyson H, Wright P (November 2002). "Cooperativity in transcription factor binding to the coactivator CREB-binding protein (CBP). The mixed lineage leukemia protein (MLL) activation domain binds to an allosteric site on the KIX domain". J. Biol. Chem. 277 (45): 43168–74. doi:10.1074/jbc.M207660200. PMID 12205094. 
  8. ^ Ernst P, Wang J, Huang M, Goodman R, Korsmeyer S (April 2001). "MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein". Mol. Cell. Biol. 21 (7): 2249–58. doi:10.1128/MCB.21.7.2249-2258.2001. PMC 86859. PMID 11259575. 
  9. ^ a b Xia Z, Anderson M, Diaz M, Zeleznik-Le N (July 2003). "MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein". Proc. Natl. Acad. Sci. U.S.A. 100 (14): 8342–7. doi:10.1073/pnas.1436338100. PMC 166231. PMID 12829790. 
  10. ^ Fair K, Anderson M, Bulanova E, Mi H, Tropschug M, Diaz M (May 2001). "Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells". Mol. Cell. Biol. 21 (10): 3589–97. doi:10.1128/MCB.21.10.3589-3597.2001. PMC 100280. PMID 11313484. 
  11. ^ Adler H, Chinery R, Wu D, Kussick S, Payne J, Fornace A et al. (October 1999). "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins". Mol. Cell. Biol. 19 (10): 7050–60. PMC 84700. PMID 10490642. 

MLL is fused to TET1 (Lorsbach et al. 2003)

Further reading[edit]

  • Marschalek R, Nilson I, Löchner K, Greim R, Siegler G, Greil J et al. (1998). "The structure of the human ALL-1/MLL/HRX gene". Leuk. Lymphoma 27 (5–6): 417–28. doi:10.3109/10428199709058308. PMID 9477123. 
  • Eguchi M, Eguchi-Ishimae M, Greaves M (2004). "The role of the MLL gene in infant leukemia". Int. J. Hematol. 78 (5): 390–401. doi:10.1007/BF02983811. PMID 14704031. 
  • Daser A, Rabbitts T (2004). "Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis". Genes Dev. 18 (9): 965–74. doi:10.1101/gad.1195504. PMID 15132992. 
  • Li Z, Liu D, Liang C (2005). "New insight into the molecular mechanisms of MLL-associated leukemia". Leukemia 19 (2): 183–90. doi:10.1038/sj.leu.2403602. PMID 15618964. 
  • Douet-Guilbert N, Morel F, Le Bris M, Sassolas B, Giroux J, De Braekeleer M (2005). "Rearrangement of MLL in a patient with congenital acute monoblastic leukemia and granulocytic sarcoma associated with a t(1;11)(p36;q23) translocation". Leuk. Lymphoma 46 (1): 143–6. doi:10.1080/104281904000010783. PMID 15621793. 

External links[edit]