KAT6A explained

K(lysine) acetyltransferase 6A (KAT6A), is an enzyme that, in humans, is encoded by the KAT6A gene.^{[1] [2]} This gene is located on human chromosome 8, band 8p11.21. ^[3]

Protein function

The KAT6A protein^[4] contains two nuclear localization domains, a C₂HC₃ zinc finger and an acetyltransferase domain. This structure suggests that KAT6A functions as a chromatin-bound acetyltransferase.^[2] KAT6A is important for the proper development of hematopoietic stem cells.^[5]

Arboleda-Tham syndrome

See main article: Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome. Arboleda-Tham syndrome (ARTHS),^[6] also referred to as KAT6A Syndrome (Arboleda-Tham Syndrome), is a rare autosomal dominant developmental disorder, caused by various missense, nonsense, and frameshift mutations in the KAT6A gene. The main characteristics of this syndrome are developmental delay, impaired intellectual development, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications. ^[7]

Further reading

• Schuler GD, Boguski MS, Stewart EA, etal . A gene map of the human genome. . Science . 274 . 5287 . 540–6 . 1996 . 8849440 . 10.1126/science.274.5287.540 . 1996Sci...274..540S . 22619 .
• Borrow J, Stanton VP, Andresen JM, etal . The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. . Nat. Genet. . 14 . 1 . 33–41 . 1996 . 8782817 . 10.1038/ng0996-33 . 205342752 .
• Carapeti M, Aguiar RC, Goldman JM, Cross NC . A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. . Blood . 91 . 9 . 3127–33 . 1998 . 9558366 . 10.1182/blood.V91.9.3127. free .
• Chaffanet M, Gressin L, Preudhomme C, etal . MOZ is fused to p300 in an acute monocytic leukemia with t(8;22). . Genes Chromosomes Cancer . 28 . 2 . 138–44 . 2000 . 10824998 . 10.1002/(SICI)1098-2264(200006)28:2<138::AID-GCC2>3.0.CO;2-2 . 12096923 .
• Champagne N, Pelletier N, Yang XJ . The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. . Oncogene . 20 . 3 . 404–9 . 2001 . 11313971 . 10.1038/sj.onc.1204114 . free .
• Kitabayashi I, Aikawa Y, Nguyen LA, etal . Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. . EMBO J. . 20 . 24 . 7184–96 . 2002 . 11742995 . 10.1093/emboj/20.24.7184 . 125775 .
• Pelletier N, Champagne N, Stifani S, Yang XJ . MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. . Oncogene . 21 . 17 . 2729–40 . 2002 . 11965546 . 10.1038/sj.onc.1205367 . free .
• 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 .
• Deguchi K, Ayton PM, Carapeti M, etal . MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP. . Cancer Cell . 3 . 3 . 259–71 . 2003 . 12676584 . 10.1016/S1535-6108(03)00051-5 . free .
• Bristow CA, Shore P . Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ. . Nucleic Acids Res. . 31 . 11 . 2735–44 . 2003 . 12771199 . 10.1093/nar/gkg401 . 156734 .
• 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 .
• Kindle KB, Troke PJ, Collins HM, etal . MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function. . Mol. Cell. Biol. . 25 . 3 . 988–1002 . 2005 . 15657427 . 10.1128/MCB.25.3.988-1002.2005 . 544007 .
• Cereseto A, Manganaro L, Gutierrez MI, etal . Acetylation of HIV-1 integrase by p300 regulates viral integration. . EMBO J. . 24 . 17 . 3070–81 . 2005 . 16096645 . 10.1038/sj.emboj.7600770 . 1201351 .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 .
• Collins HM, Kindle KB, Matsuda S, etal . MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta2 promoter: differential effects of MOZ fusion proteins on CBP- and MOZ-dependent activators. . J. Biol. Chem. . 281 . 25 . 17124–33 . 2006 . 16613851 . 10.1074/jbc.M602633200 . free .
• Lim J, Hao T, Shaw C, etal . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Kim SC, Sprung R, Chen Y, etal . Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. . Mol. Cell . 23 . 4 . 607–18 . 2006 . 16916647 . 10.1016/j.molcel.2006.06.026 . free .
• Olsen JV, Blagoev B, Gnad F, etal . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Topper M, Luo Y, Zhadina M, etal . Posttranslational acetylation of the human immunodeficiency virus type 1 integrase carboxyl-terminal domain is dispensable for viral replication. . J. Virol. . 81 . 6 . 3012–7 . 2007 . 17182677 . 10.1128/JVI.02257-06 . 1865993 .

Notes and References

1. Web site: Entrez Gene: MYST3 MYST histone acetyltransferase (monocytic leukemia) 3.
2. Borrow J, Stanton VP, Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dubé I, Frischauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE, Housman DE . The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein . Nat. Genet. . 14 . 1 . 33–41 . September 1996 . 8782817 . 10.1038/ng0996-33 . 205342752 .
3. https://www.ncbi.nlm.nih.gov/gene/7994 - KAT6A NCBI
4. omim.org/entry/601408
5. Yang XJ, Ullah M . MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells . Oncogene . 26 . 37 . 5408–19 . August 2007 . 17694082 . 10.1038/sj.onc.1210609 . free .
6. Web site: OMIM Entry - # 616268 - ARBOLEDA-THAM SYNDROME; ARTHS .
7. Kennedy, J., Goudie, D., Blair, E. et al. KAT6A Syndrome: genotype–phenotype correlation in 76 patients with pathogenic KAT6A variants. Genet Med 21, 850–860 (2019). https://doi.org/10.1038/s41436-018-0259-2