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.
Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila)
Protein MLL PDB 2j2s.png
PDB rendering based on 2j2s.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MLL ; ALL-1; CXXC7; HRX; HTRX1; KMT2A; MLL/GAS7; MLL1A; TET1-MLL; TRX1; WDSTS
External IDs OMIM159555 MGI96995 HomoloGene4338 ChEMBL: 1293299 GeneCards: MLL 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 NR, Gill HJ, Espinosa R, Patel Y, Harden A, Rubinelli P, Smith SD, LeBeau MM, Rowley JD (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 NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE (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, Leshkowitz D, Croce CM, Canaani E (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 RH, Korsmeyer SJ (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 MG, Jenner RG, Chevalier B, Nakamura T, Croce CM, Canaani E, Young RA (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 HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S (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 BA, Pronold M, Long R, Smaoui N, Slavotinek AM (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: 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 DJ, Kitabayashi I, Herr W, Cleary ML (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 NK, Zor T, Martinez-Yamout M, Dyson HJ, Wright PE (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 RH, Korsmeyer SJ (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 ZB, Anderson M, Diaz MO, Zeleznik-Le NJ (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 MO (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 HT, Chinery R, Wu DY, Kussick SJ, Payne JM, Fornace AJ, Tkachuk DC (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 (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 TH (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 ZY, Liu DP, Liang CC (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 (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]