PROSITE documentation PDOC51728Rtt109-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>), CBP/p300, Rtt109 and MYST 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.
Rtt109, also known as KAT11, is a recently characterized fungal-specific HAT that modifies histone H3 lysine 56 (H3K56) to promote genome stability and resistance to a variety of DNA-damaging agents. Rtt109 does not show sequence conservation with other known HATs and depends on association with either of two histone chaperones, Asf1 or Vps75, for HAT activity [1,2,3].
The Rtt109-type HAT domain consists of a core HAT subdomain, which binds the acetyl-CoA cofactor. A second subdomain, the activation subdomain, is tightly associated with the HAT subdomain. Autoacetylation of a lysine within the activation subdomain is required for stabilizing the interaction between the two subdomains and is essential for catalysis. The Rtt109-type HAT domain contains eight β strands and nine α helices and displays mixed three-layered α/β architecture with eight β strands sandwiched by five α helices (α1-α5) from one side, and four α helices (α6-α9) from the other side (see<PDB:2RIM>) [1,2,3].
The profile we developed covers the entire Rtt109-type HAT domain.
Last update:July 2014 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Lin C. Yuan Y.A. |
| Title | Structural insights into histone H3 lysine 56 acetylation by Rtt109. | |
| Source | Structure 16:1503-1510(2008). | |
| PubMed ID | 18707894 | |
| DOI | 10.1016/j.str.2008.07.006 |
| 2 | Authors | Tang Y. Holbert M.A. Wurtele H. Meeth K. Rocha W. Gharib M. Jiang E. Thibault P. Verreault A. Cole P.A. Marmorstein R. |
| Title | Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBP. | |
| Source | Nat. Struct. Mol. Biol. 15:738-745(2008). | |
| PubMed ID | 18568037 | |
| DOI | 10.1038/nsmb.1448 |
| 3 | Authors | Stavropoulos P. Nagy V. Blobel G. Hoelz A. |
| Title | Molecular basis for the autoregulation of the protein acetyl transferase Rtt109. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 105:12236-12241(2008). | |
| PubMed ID | 18719104 | |
| DOI | 10.1073/pnas.0805813105 |
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