|PROSITE documentation PDOC51726|
Histone acetyltransferase (HAT) enzymes play important roles in the regulation of chromatin assembly, RNA transcription, DNA repair and other DNA-templated reactions through the lysine side-chain acetylation of histones and other transcription factors. HATs fall into at least four different families based on sequence conservation within the HAT domain. This includes Gcn5/PCAF (see <PDOC51186>), p300/CBP, Rtt109 and MYST (named for the founding members MOZ, Ybf2/Sas3, Sas2 and Tip 60) families. The different HAT families contain a structurally conserved central region associated with acetyl-Coenzyme A (Ac-CoA) cofactor binding but distinct catalytic mechanisms and structurally divergent flanking regions that mediate different chromatin regulatory functions. Protein acetylation extends beyond histones to other nuclear proteins and even cytoplasmic proteins to regulate diverse biological processes including the regulation of cell cycle, vesicular trafficking, cytoskeleton reorganization and metabolism.
The MYST proteins represent the largest family of HATs. They are conserved from yeast to man and mediate diverse biological functions including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. MYST proteins have also been shown to acetylate several non-histone substrates.
The MYST-type HAT domain contains three regions: a central region associated with acetyl-CoA cofactor binding and catalysis in addition to flanking N- and C-terminal regions harboring respectively a C2HC-type zinc finger and a helix-turn-helix DNA-binding motif (see <PDB:1FY7>). The N- and C-terminal segments directly flanking the catalytic core are likely to play an important role in histone substrate binding [1,3]. The catalytic mechanism for the MYST-type HAT domain is still unresolved but seems to involve a conserved glutamate that functions to abstract a proton from lysine to promote the nucleophilic attack on the acetyl carbonyl carbon of acetyl-CoA [1,2,4,5].
Some proteins known to contain a MYST-type HAT domain are listed below:
The profile we developed covers the entire MYST-type HAT domain.Last update:
July 2014 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Yan Y. Barlev N.A. Haley R.H. Berger S.L. Marmorstein R.|
|Title||Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.|
|Source||Mol. Cell 6:1195-1205(2000).|
|2||Authors||Yang C. Wu J. Sinha S.H. Neveu J.M. Zheng Y.G.|
|Title||Autoacetylation of the MYST lysine acetyltransferase MOF protein.|
|Source||J. Biol. Chem. 287:34917-34926(2012).|
|3||Authors||Holbert M.A. Sikorski T. Carten J. Snowflack D. Hodawadekar S. Marmorstein R.|
|Title||The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting.|
|Source||J. Biol. Chem. 282:36603-36613(2007).|
|4||Authors||Yuan H. Rossetto D. Mellert H. Dang W. Srinivasan M. Johnson J. Hodawadekar S. Ding E.C. Speicher K. Abshiru N. Perry R. Wu J. Yang C. Zheng Y.G. Speicher D.W. Thibault P. Verreault A. Johnson F.B. Berger S.L. Sternglanz R. McMahon S.B. Cote J. Marmorstein R.|
|Title||MYST protein acetyltransferase activity requires active site lysine autoacetylation.|
|Source||EMBO J. 31:58-70(2012).|
|5||Authors||Decker P.V. Yu D.Y. Iizuka M. Qiu Q. Smith M.M.|
|Title||Catalytic-site mutations in the MYST family histone Acetyltransferase Esa1.|