PROSITE documentation PDOC51726
MYST-type histone acetyltransferase (HAT) domain profile


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:

  • Yeast Sas2 (Something About Silencing 2), encodes a positive regulator of transcriptional silencing.
  • Yeast Sas3, related to Sas2.
  • Yeast Esa1 (essential Sas2-related acetyltransferase), is important for G2/M cell cycle progression that is dependent on the checkpoint gene RAD9.
  • MOZ (monocytic leukemia zinc finger protein), an oncoprotein.
  • Tip60 (Tat interacting protein 60), interacts with HIV-1 Tat to augment Tat-mediated transactivation of HIV-1 gene expression.
  • Drosophila MOF (male absent from the first) is a component of the MSL complex that regulates dosage compensation.
  • Human MORF, bears strong sequence similarity to MOZ.
  • Human HBO1, interacts with the origin recognition complex.

The profile we developed covers the entire MYST-type HAT domain.

Last update:

July 2014 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

MYST_HAT, PS51726; MYST-type histone acetyltransferase (HAT) domain profile  (MATRIX)


1AuthorsYan Y. Barlev N.A. Haley R.H. Berger S.L. Marmorstein R.
TitleCrystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.
SourceMol. Cell 6:1195-1205(2000).
PubMed ID11106757

2AuthorsYang C. Wu J. Sinha S.H. Neveu J.M. Zheng Y.G.
TitleAutoacetylation of the MYST lysine acetyltransferase MOF protein.
SourceJ. Biol. Chem. 287:34917-34926(2012).
PubMed ID22918831

3AuthorsHolbert M.A. Sikorski T. Carten J. Snowflack D. Hodawadekar S. Marmorstein R.
TitleThe human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting.
SourceJ. Biol. Chem. 282:36603-36613(2007).
PubMed ID17925393

4AuthorsYuan 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.
TitleMYST protein acetyltransferase activity requires active site lysine autoacetylation.
SourceEMBO J. 31:58-70(2012).
PubMed ID22020126

5AuthorsDecker P.V. Yu D.Y. Iizuka M. Qiu Q. Smith M.M.
TitleCatalytic-site mutations in the MYST family histone Acetyltransferase Esa1.
SourceGenetics 178:1209-1220(2008).
PubMed ID18245364

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