{PDOC51726}
{PS51726; MYST_HAT}
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* MYST-type histone acetyltransferase (HAT) domain profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: July 2014 / First entry.

[ 1] Yan Y., Barlev N.A., Haley R.H., Berger S.L., Marmorstein R.
     "Crystal structure of yeast Esa1 suggests a unified mechanism for
     catalysis and substrate binding by histone acetyltransferases."
     Mol. Cell 6:1195-1205(2000).
     PubMed=11106757
[ 2] Yang C., Wu J., Sinha S.H., Neveu J.M., Zheng Y.G.
     "Autoacetylation of the MYST lysine acetyltransferase MOF protein."
     J. Biol. Chem. 287:34917-34926(2012).
     PubMed=22918831; DOI=10.1074/jbc.M112.359356
[ 3] Holbert M.A., Sikorski T., Carten J., Snowflack D., Hodawadekar S.,
     Marmorstein R.
     "The human monocytic leukemia zinc finger histone acetyltransferase
     domain contains DNA-binding activity implicated in chromatin
     targeting."
     J. Biol. Chem. 282:36603-36613(2007).
     PubMed=17925393; DOI=10.1074/jbc.M705812200
[ 4] 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.
     "MYST protein acetyltransferase activity requires active site lysine
     autoacetylation."
     EMBO J. 31:58-70(2012).
     PubMed=22020126; DOI=10.1038/emboj.2011.382
[ 5] Decker P.V., Yu D.Y., Iizuka M., Qiu Q., Smith M.M.
     "Catalytic-site mutations in the MYST family histone Acetyltransferase
     Esa1."
     Genetics 178:1209-1220(2008).
     PubMed=18245364; DOI=10.1534/genetics.107.080135

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