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Information on EC 2.3.1.48 - histone acetyltransferase and Organism(s) Saccharomyces cerevisiae and UniProt Accession Q04751
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2.3.1.48 histone acetyltransferaseIUBMB Comments
A group of enzymes acetylating histones. Several of the enzymes can also acetylate lysines in other proteins [3,4].
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Word Map
- 2.3.1.48
- rhythm
-
oscillation
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suprachiasmatic
- chromatin
-
entrain
-
night
- scn
- sleep
- melatonin
- drosophila
-
diurnal
-
pacemaker
-
locomotor
-
light-dark
- nuclei
- deacetylases
-
pineal
-
morning
-
photoperiodic
- retinal
-
draw
- hypothalamus
- hdacs
-
light-induced
- melanogaster
- photoreceptors
-
noise
-
bayesian
-
nocturnal
-
evening
-
daytime
-
deacetylation
-
coherent
-
co-activator
-
oscillatory
- dementia
-
transactivation
- flies
-
neuropeptide
-
wake
-
schedule
-
24-hour
-
pulses
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circuit
- medicine
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lengthen
- molecular biology
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trichostatin
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mood
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verbal
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neuropsychological
- drug development
- tick
- analysis
- pharmacology
The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
clock, histone acetyltransferase, n-acetyltransferase, tip60, histone acetyltransferases, cbp/p300, creb-binding protein, ep300, crebbp, creb binding protein, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetyltransferase, histone
-
-
-
-
Esa1
factor acetyltransferase
-
enzyme form A is also able to acetylate nonhistone proteins, mostly transcription factors, overview
FAT
-
when acetylating nonhistone transcription factor proteins, factor specific, overview
GNAT-related histone acetyltransferase complex
-
SAGA, ADA or HAT-A2
HAT
histone acetokinase
-
-
-
-
histone acetylase
-
-
-
-
histone acetyltransferase
histone transacetylase
-
-
-
-
KAT
KAT11
lysine acetyltransferase
MYST-related histone acetyltransferase complex
-
NuA4, NuA3 or ASA(SAS-I)
NuA4
nucleosome-histone acetyltransferase
-
-
-
-
Rtt109
additional information
HAT
-
-
NuA4
the NuA4 histone acetyltransferase complex is composed of at least ACT1, ARP4, EAF3, EAF5, EAF6, EAF7, EPL1, ESA1, SWC4, TRA1, VID21, YAF9 and YNG2 subunits
additional information
-
enzymes with histone acetyltransferase and transcription cofactor activity belong to the MYST protein family
additional information
-
enzymes with histone acetyltransferase and transcription cofactor activity belong to the MYST protein family
additional information
-
enzymes with histone acetyltransferase and transcription cofactor activity belong to the MYST protein family
additional information
-
Esa1 and MOZ belong to the MYST family of histone acetyltransferases
additional information
-
Hat1, together with Hat2 and Hif1, forms the histone acetyltransferase B, HAT-B, complex
additional information
-
the enzyme belongs to the MYST acetyltransferase family
additional information
-
the enzyme belongs to the MYST family histone acetyltransferases which is divided in three sub-families, overview
additional information
-
type A enzymes are localized in the nuclei and acetylate nucleosomal histones as well as nonhistone proteins, type B enzymes can be found in the cytoplasmic fraction and are responsible for acetylation of newly synthesized histones before their translocation into the nucleus for chromatin assembly during DNA replication
additional information
-
type A enzymes can be grouped into different families based on amino acid sequence comparison and binding motifs, overview
additional information
the enzyme belongs to the MYST family histone acetyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
acetylation of lysine 5, 8, 12, and 16 of free histone H4
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
mechanisms
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
ternary complexed mechanism for PCAF and Gnc5
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
enzymes are also active as transcription coactivators and corepressors of transcription factors in gene regulation, acetylation of transcription factors, overview
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
PCAF and Gcn5 protein, fully ordered Bi-Bi kinetic mechanism with acetyl-CoA binding before histone H3
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
binding motifs
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
ordered sequential catalytic mechanism of the MYST HAT with a direct-attack mechanism and direct acetyl transfer mechanism, not mediated by Cys304, within an Esa1acetyl-CoAhistone ternary complex, acetyl-CoA binds first and CoA is the last product released
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
conserved catalytic mechanisms of HATs, overview. p300 utilizes a special type of sequential mechanism with a short-lived ternary complex, known as a Theorell-Chance mechanism. For Gcn5, p/CAF, and p300, only 3 to 5 residues on either side of the substrate lysine are required for efficient binding and catalysis by the catalytic domain
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
non-processive mechanism, where the NuA4 histone acetyltransferasecomplex dissociates from substrate after each acetylation event
-
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
sequential mechanism in which acetyl-CoA and H3 bind to a complex of isoform Rtt109 and histone chaperone Vps75 without obligate order, followed by the direct attack of the unprotonated epsilon-amino group on acetyl-CoA, transferring the acetyl-group to H3 lysine residues The chemical attack of substrate lysine on the bound acetyl-CoA is the rate-limiting step of catalysis
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:[protein]-L-lysine acetyltransferase
A group of enzymes acetylating histones. Several of the enzymes can also acetylate lysines in other proteins [3,4].
CAS REGISTRY NUMBER
COMMENTARY
9054-51-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + histone H2A
Nalpha-acetylated-histone H2A + CoA
-
-
-
?
acetyl-CoA + histone H4
Nalpha-acetylated-histone H4 + CoA
acetylation of N-terminal Ser
-
-
?
4 acetyl-CoA + histone H4
4 CoA + tetraacetylhistone H4
-
-
NuA4 randomly acetylates free and nucleosomal H4, with a small preference for lysines 5, 8, and 12 over 16
-
?
acetyl-CoA + histone H3 tail peptide
CoA + acetylhistone H3 peptide
H3 peptide substrate, amino acid sequence ARTKQTARKSTGGKAPRKQL
-
-
?
acetyl-CoA + histone H3-peptide
CoA + acetylhistone H3 -peptide
-
-
-
-
?
acetyl-CoA + histone H3-peptide
CoA + acetylhistone H3-peptide
-
-
-
-
?
acetyl-CoA + histone H4
peptide CoA + acetylhistone H4 peptide
-
-
-
?
acetyl-CoA + protamine sulfate
?
-
enzyme form A, not enzyme form B
-
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine
CoA + [histone H3]-N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine14
CoA + [histone H3]-N6-acetyl-L-lysine14
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine23
CoA + [histone H3]-N6-acetyl-L-lysine23
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine56
CoA + [histone H3]-N6-acetyl-L-lysine56
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine9
CoA + [histone H3]-N6-acetyl-L-lysine9
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine12
CoA + [histone H4]-N6-acetyl-L-lysine12
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine5
CoA + [histone H4]-N6-acetyl-L-lysine5
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine8
CoA + [histone H4]-N6-acetyl-L-lysine8
-
-
-
?
activated RNA polymerase II transcriptional coactivator p15 + 4-pentynoyl-CoA
?
-
-
-
-
?
histone H2A + acetyl-CoA
acetyl-histone H2A + CoA
-
acetylation of the tail of the histone, the enzyme is organized in the NuA4 subcomplex acting on the nucleosome, overview
-
-
?
histone H2B + acetyl-CoA
acetyl-histone H2B + CoA
-
acetylation of the tail of the histone, the enzyme is organized in the catalytic Ada2/Ada3/Gcn5 subcomplex of SAGA acting on the nucleosome, overview
-
-
?
histone H3 tail peptide + acetyl-CoA
acetyl-histone H3 tail peptide + CoA
-
-
-
-
?
isoform 1 of DNA polymerase zeta catalytic subunit + 4-pentynoyl-CoA
?
-
-
-
-
?
isoform 1 of transcription factor BTF3 + 4-pentynoyl-CoA
?
-
-
-
-
?
piccoloNuA4 peptide + acetyl-CoA
acetyl-piccoloNuA4 peptide + CoA
the peptide is part of the physiologic enzme complex, overview
-
-
?
piccoloNuA4 peptide + propionyl-CoA
propionyl-piccoloNuA4 peptide + CoA
-
-
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
chicken erythrocyte histones, enzyme form A and B
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
a group of enzymes with differing specificity towards histone acceptors, specificity of different enzyme forms
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
a group of enzymes with differing specificity towards histone acceptors, specificity of different enzyme forms
-
r
acetyl-CoA + histone
CoA + acetylhistone
-
Esa1 protein is involved in cell cycle regulation
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
involved in chromatin remodeling and DNA repair
-
r
acetyl-CoA + histone
CoA + acetylhistone
-
histone H3 is the preferred substrate
-
r
acetyl-CoA + histone
CoA + acetylhistone
-
neutralization of positively charged lysine residues by acetylation lowering the affinity of histone octamers for the negatively charged DNA
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
the acetyl groups function as signals for interaction of histones with other regulatory proteins, chromatin remodeling
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
histone acetylation on Lys16 by Sas2
-
-
?
acetyl-CoA + histone H2A
CoA + acetylhistone H2A
-
NuA4-like protein acetylates histone H4 and H2A
-
?
acetyl-CoA + histone H2B
CoA + acetylhistone H2B
-
histone H2B: preferred substrate of enzyme form A
-
?
acetyl-CoA + histone H2B
CoA + acetylhistone H2B
-
GNAT-related histone acetyltransferase complexes SAGA, ADA or H2B
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
-
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Gcn5 protein: specific for Lys14 of histone H3
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Gcn5 protein: preferred substrate, acetylation at Lys14
-
r
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
histone H3: preferred substrate
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
histone H3 preferred substrate of enzyme form A
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
recombinant and native SAS complex acetylates Lys14
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
GNAT-related histone acetyltransferase complexes SAGA, ADA or HAT-A2, MYST-related histone acetyltransferase complex NuA3
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
strong preference for free histones relative to chromatin substrate
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
acetylation of Lys56
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Rtt109 association with distinct histone chaperones directs substrate selection between N-terminal lysines, H3K9, H3K23, and those within the histone fold domain, H3K56
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Rtt109 is specific for histone H3, acetylation at Lys9 and Lys56. RTT109 has functions in addition to maintaining genome stability
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Rtt109 association with distinct histone chaperones directs substrate selection between N-terminal lysines, H3K9, H3K23, and those within the histone fold domain, H3K56. The sequence G-K-X-P within histone H3, which includes the primary Gcn5 substrate K14, makes several key contacts within the active site that are conserved with other GNAT members
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Rtt109 is specific for histone H3, acetylation at Lys9 and Lys56
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
acetylation at Lys18
-
-
?
acetyl-CoA + histone H3 peptide
CoA + acetylhistone H3 peptide
-
Lys14 of histone H3 and a peptide containing Lys14 thereof are the preferred substrates for Gnc5 and PCAF protein, as well as Gnc5 and PCAF catalytic domain
-
?
acetyl-CoA + histone H3 peptide
CoA + acetylhistone H3 peptide
-
peptides H3p19, H3p27, H3p11 are substrates for the catalytic domain of Gcn5 and PCAF
-
?
acetyl-CoA + histone H3 peptide
CoA + acetylhistone H3 peptide
-
peptide H3p20
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
Gcn5 protein acetylates H4 when purified and presented separately to the enzyme at Lys8 and Lys16
-
r
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
NuA4-like protein acetylates histone H4 and H2A
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
SAS complex, native and recombinant, acetylates Lys16
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
enzyme form B has a marked specificity for histone H4
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
histone H4 is the preferred substrate
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
histone H4 is the preferred substrate
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
histone H4 is the preferred substrate
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
acetylation of histone H4 by NuA4 is required for the cellular resistance to spindle stress. The NuA4 histone acetyltransferase subunit Yaf9, is required for the cellular response to spindle stress in yeast
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
exclusively acetylates of Lys16 of histone H4, the enzyme is required for bulk of H4 lysine 16 acetylation in vivo, role of SAS complex in antagonizing the speading of Sir proteins at silent loci in Saccharomyces cerevisiae
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
the level of HAT-B-dependent acK12H4 may be very low under normal growth condition
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
acetyltion of Lys16, acetylates free histones and weakly acetylates nucleosomes
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
MYST-related histone acetyltransferase complex NuA4 or SAS(SAS-I)
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
specifically acetylates Lys12, and to a lesser extent Lys5 of free, non-chromatin-bound histone H4
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
both Lys12 and Lys5 of soluble, non-chromatin-bound histone H4 are in vivo targets of acetylation for the yeast HAT-B enzyme. Lys12/Lys5-acetylated histone H4 is bound to the HAT-B complex in the soluble cell fraction. Exchange of Lys for Arg at position 12 of histone H4 do not interfere with histone H4 association with the complex, but prevented acetylation on Lys5 by the HAT-B enzyme, in vivo as well as in vitro
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
full-length histone H4 is acetylated 2000fold faster than histone tail peptides
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
substrates are synthetic N-terminal H4 peptides. The HAT-B complex acetylates only Lys12, recombinant Hat1 is able to modify Lys12 and Lys5. Exchange of Lys for Arg at position 12 of histone H4 does not interfere with histone H4 association with the complex, but prevents acetylation on Lys5 by the HAT-B enzyme, in vivo as well as in vitro
-
-
?
acetyl-CoA + [histone H4]-L-lysine
CoA + [histone H4]-N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine
CoA + [histone H4]-N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + [protein]-L-lysine
CoA + [protein]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [protein]-L-lysine
CoA + [protein]-N6-acetyl-L-lysine
-
-
-
?
histone + acetyl-CoA
acetyl-histone + CoA
-
key enzyme in post-translational modification of histones associated with transcriptionally active genes
-
-
?
histone H3 + acetyl-CoA
acetyl-histone H3 + CoA
-
acetylation of the tail of the histone, the enzyme is organized in the catalytic Ada2/Ada3/Gcn5 subcomplex of SAGA acting on the nucleosome, overview
-
-
?
histone H4 + acetyl-CoA
acetyl-histone H4 + CoA
-
acetylation of the tail of the histone, the enzyme is organized in the NuA4 subcomplex acting on the nucleosome, overview
-
-
?
additional information
?
-
no acetylation of adrenocorticotropin or a H3 peptide
-
-
?
additional information
?
-
-
HeLa nucleosome or core histones are no substrate for recombinant SAS complex
-
-
?
additional information
?
-
-
for acetylation activity of Sas2, Sas4 is absolutely required, while Sas5 stimulate
-
-
?
additional information
?
-
-
Gcn5 is a coactivator of transcription
-
-
?
additional information
?
-
-
Gcn5 and PCAF protein are transcription cofactors
-
-
?
additional information
?
-
-
Gcn5 and PCAF protein are transcription cofactors
-
-
?
additional information
?
-
-
Gcn5 and PCAF protein are transcription cofactors
-
-
?
additional information
?
-
-
Gcn5 and PCAF protein are transcription cofactors
-
-
?
additional information
?
-
-
enzyme activity is regulated by phosphorylation and interaction with other regulating protein factors
-
-
?
additional information
?
-
-
MYST-related histone acetyltransferase complex NuA4: required for cell growth, required for p53-dependent transcription activation in yeast, presumably through its Yng2 subunit, homolog of the tumor suppressor ING1. GNAT-related histone acetyltransferase complex SAGA can stimulate Gal4-VP16 activation in a manner dependent on HAT activity. D´SAGA can be recruited by several yeast activators. SAGA is targeted to promoter regions proximal to the activator binding site. Once targeted, SAGA acetylates histone h3 in the vicinity of the promoter. Targeted acetylation by SAGA stabilizes its binding and that of a targeted SWI/SNF chromatin-remodeling complex. SAGA is required for both activation of the yeast ARG1 promoter by Gcn4 activator and repression by the ArgR/Mcm1 repressor complex
-
-
?
additional information
?
-
in the absence of histone acceptor, slow rates of enzyme autoacetylation and of CoA formation occur
-
-
?
additional information
?
-
-
Esa1 is the catalytic subunit of at least two multiprotein complexes, NuA4 and Piccolo NuA4, picNuA4
-
-
?
additional information
?
-
-
HATs perform a conserved mechanism of acetyl-transfer, where the lysine-containing substrate directly attacks enzyme-bound acetyl-CoA. The ability of HATs to form distinct multi-subunit complexes provide a means to regulate HAT activity by altering substrate specificity, targeting to specific loci, enhancing acetyltransferase activity, restricting access of non-target proteins, and coordinating the multiple enzyme activities of the complex
-
-
?
additional information
?
-
-
HBO1, Sas2 and Sas3 are involved in transcriptional repression enhancing Sir1-mediated epigenetic gene silencing. NuA3 and NuA4 complexes contain the MYST HATs Sas3 and Esa1, respectively. Sas2 histone acetylation of H4K16 opposed by Sir2 deacetylation of H4K16 at the euchromatin/heterochromatin interface maintains the boundary between regions of transcriptionally active and silent telomeric chromatin. Esa1 plays a role in maintaining the integrity of the DNA, rather than open chromatin structure and high-level transcriptional activity
-
-
?
additional information
?
-
-
in addition to Asf1, Rtt109 is also functionally linked to Rtt101, Mms1, and Mms22
-
-
?
additional information
?
-
-
Rtt109 facilitates error-free replication to prevent CAG/CTG repeat contractions. The Rtt107/Rtt101 complex is recruited to stalled replication forks in an Rtt109-dependent manner
-
-
?
additional information
?
-
-
soluble histone H4 Hat1-dependently acetylated on Lys12 is present in cells arrested at all cell cycle stages, G1, S, G2/M and also G0. Histone H3 seems to be no substrate for the HAT-B complex
-
-
?
additional information
?
-
-
Gcn5 and p300 appear to be constituitive HATs that do not require helper proteins to exhibit full catalytic activity. Esa1 and Rtt109 represent low-activity HATs that are stimulated by regulatory helper proteins, Yng2-Epl1 and Vps75/Asf1, respectively. p300/CBP exhibits the broadest protein specificity, p300 prefers histone acetylation sites with a positive charge in the -3 or +4 position. Ability of some HATs to utilize longer chain acyl-CoA, i.e. propionyl-CoA
-
-
?
additional information
?
-
-
histone chaperone Vps75 acts as activiating subunit. The rate-determining step of the activated complex is the transfer of the acetyl group from acetyl-CoA to the acceptor lysine residue. Vps75 stimulates catalysis more than 250fold, not by contributing a catalytic base, but by stabilizing the catalytically active conformation of enzyme Rtt109
-
-
?
additional information
?
-
-
removal of lysine residues does not substantially affect the ability of NuA4 histone actyltransferase complex to acetylate remaining sites, and insertion of an additional lysine into the substrate histone H4 tail leads to rapid quintuple-acetylation. Conversion of the native histone H2A tail to an H4-like sequence results in enhanced multi-site acetylation. NuA4's site selectivity is dictated by accessibility on the nucleosome surface, the relative proximity from the histone fold domain, and a preference for intervening glycine residues with a minimal (n + 2) spacing between lysines
-
-
?
additional information
?
-
NuA4 targets histone and nonhistone proteins
-
-
-
additional information
?
-
-
NuA4 targets histone and nonhistone proteins
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview. Hpa3 also acts as D-amino-acid N-acetyltransferase, EC 2.3.1.36
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview. Hpa3 also acts as D-amino-acid N-acetyltransferase, EC 2.3.1.36
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview. Hpa3 also acts as D-amino-acid N-acetyltransferase, EC 2.3.1.36
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview. Hpa3 also acts as D-amino-acid N-acetyltransferase, EC 2.3.1.36
-
-
-
additional information
?
-
high-resolution mass spectrometry investigations identifies 1750 proteins as substrates of the posttranslational modification of acetylation, overview. Hpa3 also acts as D-amino-acid N-acetyltransferase, EC 2.3.1.36
-
-
-
additional information
?
-
Nut1 is a mediator of RNA polymerase II transcription subunit 5, that also has histone acetylase activity
-
-
-
additional information
?
-
Nut1 is a mediator of RNA polymerase II transcription subunit 5, that also has histone acetylase activity
-
-
-
additional information
?
-
Nut1 is a mediator of RNA polymerase II transcription subunit 5, that also has histone acetylase activity
-
-
-
additional information
?
-
Nut1 is a mediator of RNA polymerase II transcription subunit 5, that also has histone acetylase activity
-
-
-
additional information
?
-
Nut1 is a mediator of RNA polymerase II transcription subunit 5, that also has histone acetylase activity
-
-
-
additional information
?
-
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
-
-
additional information
?
-
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
-
-
additional information
?
-
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
-
-
additional information
?
-
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
-
-
additional information
?
-
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4 acetyl-CoA + histone H4
4 CoA + tetraacetylhistone H4
-
-
NuA4 randomly acetylates free and nucleosomal H4, with a small preference for lysines 5, 8, and 12 over 16
-
?
acetyl-CoA + [alpha-tubulin]-L-lysine
CoA + [alpha-tubulin]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine
CoA + [histone H3]-N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine14
CoA + [histone H3]-N6-acetyl-L-lysine14
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine23
CoA + [histone H3]-N6-acetyl-L-lysine23
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine56
CoA + [histone H3]-N6-acetyl-L-lysine56
-
-
-
?
acetyl-CoA + [histone H3]-L-lysine9
CoA + [histone H3]-N6-acetyl-L-lysine9
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine12
CoA + [histone H4]-N6-acetyl-L-lysine12
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine5
CoA + [histone H4]-N6-acetyl-L-lysine5
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine8
CoA + [histone H4]-N6-acetyl-L-lysine8
-
-
-
?
piccoloNuA4 peptide + acetyl-CoA
acetyl-piccoloNuA4 peptide + CoA
the peptide is part of the physiologic enzme complex, overview
-
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
Esa1 protein is involved in cell cycle regulation
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
involved in chromatin remodeling and DNA repair
-
r
acetyl-CoA + histone
CoA + acetylhistone
-
histone H3 is the preferred substrate
-
r
acetyl-CoA + histone
CoA + acetylhistone
-
neutralization of positively charged lysine residues by acetylation lowering the affinity of histone octamers for the negatively charged DNA
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
the acetyl groups function as signals for interaction of histones with other regulatory proteins, chromatin remodeling
-
?
acetyl-CoA + histone
CoA + acetylhistone
-
histone acetylation on Lys16 by Sas2
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
acetylation of Lys56
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Rtt109 association with distinct histone chaperones directs substrate selection between N-terminal lysines, H3K9, H3K23, and those within the histone fold domain, H3K56
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
Rtt109 is specific for histone H3, acetylation at Lys9 and Lys56. RTT109 has functions in addition to maintaining genome stability
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
-
acetylation at Lys18
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
acetylation of histone H4 by NuA4 is required for the cellular resistance to spindle stress. The NuA4 histone acetyltransferase subunit Yaf9, is required for the cellular response to spindle stress in yeast
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
exclusively acetylates of Lys16 of histone H4, the enzyme is required for bulk of H4 lysine 16 acetylation in vivo, role of SAS complex in antagonizing the speading of Sir proteins at silent loci in Saccharomyces cerevisiae
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
the level of HAT-B-dependent acK12H4 may be very low under normal growth condition
-
-
?
acetyl-CoA + histone H4
CoA + acetylhistone H4
-
both Lys12 and Lys5 of soluble, non-chromatin-bound histone H4 are in vivo targets of acetylation for the yeast HAT-B enzyme. Lys12/Lys5-acetylated histone H4 is bound to the HAT-B complex in the soluble cell fraction. Exchange of Lys for Arg at position 12 of histone H4 do not interfere with histone H4 association with the complex, but prevented acetylation on Lys5 by the HAT-B enzyme, in vivo as well as in vitro
-
-
?
acetyl-CoA + [histone H4]-L-lysine
CoA + [histone H4]-N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + [histone H4]-L-lysine
CoA + [histone H4]-N6-acetyl-L-lysine
-
-
-
?
acetyl-CoA + [protein]-L-lysine
CoA + [protein]-N6-acetyl-L-lysine
-
-
-
-
?
acetyl-CoA + [protein]-L-lysine
CoA + [protein]-N6-acetyl-L-lysine
-
-
-
?
histone + acetyl-CoA
acetyl-histone + CoA
-
key enzyme in post-translational modification of histones associated with transcriptionally active genes
-
-
?
additional information
?
-
-
enzyme activity is regulated by phosphorylation and interaction with other regulating protein factors
-
-
?
additional information
?
-
-
MYST-related histone acetyltransferase complex NuA4: required for cell growth, required for p53-dependent transcription activation in yeast, presumably through its Yng2 subunit, homolog of the tumor suppressor ING1. GNAT-related histone acetyltransferase complex SAGA can stimulate Gal4-VP16 activation in a manner dependent on HAT activity. D´SAGA can be recruited by several yeast activators. SAGA is targeted to promoter regions proximal to the activator binding site. Once targeted, SAGA acetylates histone h3 in the vicinity of the promoter. Targeted acetylation by SAGA stabilizes its binding and that of a targeted SWI/SNF chromatin-remodeling complex. SAGA is required for both activation of the yeast ARG1 promoter by Gcn4 activator and repression by the ArgR/Mcm1 repressor complex
-
-
?
additional information
?
-
-
Esa1 is the catalytic subunit of at least two multiprotein complexes, NuA4 and Piccolo NuA4, picNuA4
-
-
?
additional information
?
-
-
HATs perform a conserved mechanism of acetyl-transfer, where the lysine-containing substrate directly attacks enzyme-bound acetyl-CoA. The ability of HATs to form distinct multi-subunit complexes provide a means to regulate HAT activity by altering substrate specificity, targeting to specific loci, enhancing acetyltransferase activity, restricting access of non-target proteins, and coordinating the multiple enzyme activities of the complex
-
-
?
additional information
?
-
-
HBO1, Sas2 and Sas3 are involved in transcriptional repression enhancing Sir1-mediated epigenetic gene silencing. NuA3 and NuA4 complexes contain the MYST HATs Sas3 and Esa1, respectively. Sas2 histone acetylation of H4K16 opposed by Sir2 deacetylation of H4K16 at the euchromatin/heterochromatin interface maintains the boundary between regions of transcriptionally active and silent telomeric chromatin. Esa1 plays a role in maintaining the integrity of the DNA, rather than open chromatin structure and high-level transcriptional activity
-
-
?
additional information
?
-
-
in addition to Asf1, Rtt109 is also functionally linked to Rtt101, Mms1, and Mms22
-
-
?
additional information
?
-
-
Rtt109 facilitates error-free replication to prevent CAG/CTG repeat contractions. The Rtt107/Rtt101 complex is recruited to stalled replication forks in an Rtt109-dependent manner
-
-
?
additional information
?
-
-
soluble histone H4 Hat1-dependently acetylated on Lys12 is present in cells arrested at all cell cycle stages, G1, S, G2/M and also G0. Histone H3 seems to be no substrate for the HAT-B complex
-
-
?
additional information
?
-
NuA4 targets histone and nonhistone proteins
-
-
-
additional information
?
-
-
NuA4 targets histone and nonhistone proteins
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetyl-CoA
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
NaCl
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(propan-2-ylidene)hydrazine
-
i.e. BF1, shows substrate selectivity for histone H3 acetylation and inhibitory activity in vitro on recombinant HATs Gcn5 and p300. Both global acetylation of histone H3 and specific acetylation at lysine 18 (H3AcK18) are lowered by BF1 treatment
3-quinolinecarboxylic acid ethyl ester
-
effects in vivo, inhibitory effect on the transcription is not fully GCN5-specific, overview
acetylated histone H3 peptide
-
noncompetitive versus acetyl-CoA and histone H3
-
desulfo-coenzyme A
-
dead-end inhibitor, competitive versus acetyl-CoA, Gcn5 protein
DNA
-
enzyme form A activated by low concentrations, enzyme form B inhibited
ethyl 2-methylquinoline-3-carboxylate
-
effects in vivo, inhibitory effect on the transcription is fully GCN5-specific, overview
p-chloromercuribenzoate
-
enzyme form B less sensitive than enzyme form A
additional information
-
screening for small molecule inhibitors reducing the cell growth, overview
-
additional information
-
protein factors such as E1A and Nap1 can modulate p300/CBP HAT activity
-
additional information
-
synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors active both in vitro and in vivo, overview
-
additional information
analysis of KATi, bisubstrate analogues, natural compounds and synthetic derivatives, mechanism of action, structure-activity relationships, and pharmacokinetic/pharmacodynamic properties, overview
-
additional information
analysis of KATi, bisubstrate analogues, natural compounds and synthetic derivatives, mechanism of action, structure-activity relationships, and pharmacokinetic/pharmacodynamic properties, overview
-
additional information
analysis of KATi, bisubstrate analogues, natural compounds and synthetic derivatives, mechanism of action, structure-activity relationships, and pharmacokinetic/pharmacodynamic properties, overview
-
additional information
analysis of KATi, bisubstrate analogues, natural compounds and synthetic derivatives, mechanism of action, structure-activity relationships, and pharmacokinetic/pharmacodynamic properties, overview
-
additional information
analysis of KATi, bisubstrate analogues, natural compounds and synthetic derivatives, mechanism of action, structure-activity relationships, and pharmacokinetic/pharmacodynamic properties, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DNA
-
enzyme form A activated by low concentration, enzyme form B inhibited
methylated histone
-
stimulates interaction of NuA4 complex with histone
NuA4
-
cooperation with the NuA4 complex to enhance its functions but independent contribution to acetylation
-
SAGA
-
cooperation with the Gcn5 complex to enhance its functions but independent contribution to acetylation
-
Sas4
-
absolutely required for acetylation activity of Sas2 in SAS complex
-
Vps75/Asf1
-
helper proteins required by Rtt109 for full catalytic activity. Stimulation of Rtt109 activity by Vps75 results in 50fold increase of the kcat value with unaltered Km
-
Yng2/Epl1
-
helper proteins required by Esa1 for full catalytic activity. Esa1 minimally requires Yng2 and Epl1 for full catalytic activity and nucleosome recognition
-
VPS75
-
Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by histone chaperone Vps75, Asf1, and Vps75 are both required for acetylation of Lys9 on H3 in vivo by Rtt109, whereas acetylation of Lys56 on H3 in vivo requires only Asf1
-
additional information
-
phosphorylation of histone H3 enhances Gcn5 enzyme activity
-
additional information
-
Hat1 and Hat2, but not Hif1, of the HAT-B complex are required for the Lys12/Lys5-specific acetylation and for histone H4 binding
-
additional information
-
protein factors such as E1A and Nap1 can modulate p300/CBP HAT activity. Rtt109 requires a histone chaperone for efficient catalysis. HATs form multisubunit complexes, and HAT interacting partners appear to regulate HAT activity by altering substrate specificity, targeting to specific loci, enhancing acetyltransferase activity, restricting access of non-target proteins, and coordinating the multiple enzyme activities of the complex
-
additional information
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
additional information
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
additional information
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
additional information
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
additional information
Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0023
acetyl-CoA
-
wild-type, presence of 0.4 equivalents of chaperone Vps75, pH 7.5, 25°C
0.0039
acetyl-CoA
-
wild-type, presence of 0.2 equivalents of chaperone Vps75, pH 7.5, 25°C
0.0063
acetyl-CoA
-
wild-type, presence of 1 equivalent of chaperone Vps75, pH 7.5, 25°C
0.0065
acetyl-CoA
-
wild-type, presence of 2 equivalents of chaperone Vps75, pH 7.5, 25°C
0.0065
acetyl-CoA
-
wild-type, presence of 8 equivalents of chaperone Vps75, pH 7.5, 25°C
0.044
histone H3 tail peptide
mutant D287A/D288A, pH 7.5, 25°C
-
additional information
additional information
-
Gcn5 protein mutants
-
additional information
additional information
steady-state kinetic analyses, kinetic mechanism
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
Gcn5 protein mutants
-
0.031
acetyl-CoA
-
mutant E374A/E378A/D301K, presence of chaperone Vps75, pH 7.5, 25°C
0.035
acetyl-CoA
-
mutant E374K/E378K, presence of chaperone Vps75, pH 7.5, 25°C
0.07
acetyl-CoA
-
wild-type, wild-type, presence of 0.2 equivalents of chaperone Vps75, pH 7.5, 25°C
0.08
acetyl-CoA
-
wild-type, presence of 0.4 equivalents of chaperone Vps75, pH 7.5, 25°C
0.16
acetyl-CoA
-
mutant E374A/E378A, presence of chaperone Vps75, pH 7.5, 25°C
0.28
acetyl-CoA
-
wild-type, presence of 1 equivalent of chaperone Vps75, pH 7.5, 25°C
0.48
acetyl-CoA
-
wild-type, presence of 2 equivalents of chaperone Vps75, pH 7.5, 25°C
0.62
acetyl-CoA
-
wild-type, presence of 8 equivalents of chaperone Vps75, pH 7.5, 25°C
0.0011
histone H3 tail peptide
mutant D287A/D288A, pH 7.5, 25°C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
18
acetyl-CoA
-
wild-type, presence of 0.2 equivalents of chaperone Vps75, pH 7.5, 25°C
35
acetyl-CoA
-
wild-type, presence of 0.4 equivalents of chaperone Vps75, pH 7.5, 25°C
44
acetyl-CoA
-
wild-type, presence of 1 equivalent of chaperone Vps75, pH 7.5, 25°C
73
acetyl-CoA
-
wild-type, presence of 2 equivalents of chaperone Vps75, pH 7.5, 25°C
97
acetyl-CoA
-
wild-type, presence of 8 equivalents of chaperone Vps75, pH 7.5, 25°C
0.025
histone H3 tail peptide
mutant D287A/D288A, pH 7.5, 25°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
methods for the analysis of histone acetyltransferase activity in vitro
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 9.5
-
less than 10% of activity maximum below pH 6.5 and above pH 9.5
additional information
pH profiles of wild-type and mutant enzymes
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
fairly constant levels of Hat1 protein throughout the cell cycle, soluble histone H4 Hat1-dependently acetylated on Lys12 is present in cells arrested at all cell cycle stages, G1, S, G2/M and also G0
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
recruitment of Hat1p to chromatin is linked to DNA double-strand breaks, e.g. at the MAT locus, nuclear Hat1p-associated histone chaperone Hif1p is also recruited to an endonuclease HO-induced double-strand break with a similar distribution, the enzyme influences the chromatin structure at double-strand breaks, its recruitment to double-strand breaks is independent of recombinational repair, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
-
acetyltransferases are very well conserved through evolution
evolution
the enzyme belongs to the nuclear receptors coactivators. Fungal enzyme Rtt109 shows low sequence similarity to members of other KAT families. It is comparable to p300 in terms of its tertiary structure, but has a different catalytic mechanism
evolution
the enzyme TAF1/TBP belongs to the components of transcription factor complexes
evolution
the KATs belong to the enzyme families Gcn5 (KAT2A), PCAF (p300/CBP associated factor, KAT2B), Elp3 (KAT9), Hpa2 (KAT10), Hpa3, and Nut1. The common feature is the presence of four conserved 15-33 amino acid motifs indicated as A, B, C and D, in addition to various chromo- and bromodomains that can bind methylated or acetylated lysines, respectively. The A motif is the most conserved and contains the R/Q-X-X-G-X-G/A sequence that is essential for acetyl-CoA recognition and binding. Despite the structural similarities that characterize an enzyme family, the N- and C-terminal domains are quite different, and allow each enzyme to be specific for a particular substrate
malfunction
-
cells lacking RTT109 have a high level of CAG/CTG repeat contractions and a twofold increase in breakage at CAG/CTG repeats
malfunction
-
GCN5 deletion differently affects the growth of two strains, i.e. W303-1A and D273-10B/A1. The defective mitochondrial phenotype is related to a marked decrease in mtDNA content, which also involves the deletion of specific regions of the molecule. W303-1A cells deleted of the GCN5 gene show a thermosensitive phenotype. The ratio of mtDNA to nuclear DNA is strongly decreased (50 times) in the W303-1A mutant cells compared to wild-type cells. This defect is not observed in the D273-10B/1A cells. The different level of mtDNA in the two gcn5DELTA strains is consistent with their different phenotypes and with the higher respiratory competence of W303-1A compared to D273-10B/A1 cells. Deletion of GCN5 differently affects fermentative and respirative growth. The dynamics of mtDNA depletion during cell duplication indicates the loss of specific regions
malfunction
NuA4 mutants induce the expression of the inositol-3-phosphate synthase gene, INO1, which leads to excessive accumulation of inositol, a key metabolite used for phospholipid biosynthesis, called an Opi- phenotype. High-throughput genomic screens have identified many other mutants that derepress INO1 transcription, besides Opil mutants, and cause excessive accumulation of inositol, including mutants of the NuA4 complex (EAF1, EAF3, EAF5, EAF7, YAF9, and ESA1). NuA4 mutants exacerbate the growth defects of sec14-1ts under inositol-depleted conditions. As NuA4 mutants exhibit a derepression of INO1 and excessive inositol production, or Opi- phenotype, NuA4 mutants suppress the growth defect in sec14-1ts under inositol-depleted conditions. Lipid droplet dynamics are impaired in eaf1DELTA cells. The eaf1DELTA mutant negative genetic interaction with sec14-1ts and the decreased lipid droplet staining in eaf1D originate from defects within the fatty acid biosynthesis pathway
metabolism
-
acetylation, which targets a broad range of histone and non-histone proteins, is a reversible mechanism and plays a critical role in eukaryotic genes activation/deactivation
metabolism
analysis of connections between NuA4, inositol, and Sec14, which is a phosphatidylinositol/phosphatidylcholine transfer protein. Overview of phospholipid metabolism. Sec14 (UniProt ID P24280) is an essential phospholipid-binding protein that coordinates the metabolism of phosphatidylinositol-4-phosphate with phosphatidylcholine (PC) at the Golgi to create a lipid environment necessary for trafficking events
metabolism
exogenous acetate and reduced expression of ACC1 decreases glucose-deprived stress granule formation
metabolism
stress granule formation is a conserved cellular stress response. Elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. NuA4 mutant cells exhibit reduced Pab1-GFP cytoplasmic foci upon glucose deprivation. Suppression of glucose-deprived stress granule formation by eaf7DELTA mutants is mediated by increased acetyl-CoA. Acc1 activity is reduced in eaf1DELTA cells
physiological function
-
Esa1 catalytic HAT activity is essential in yeast binding acetyl-CoA or lysine substrates and positively regulating the activities of NuA4 and Piccolo NuA4, Esa1 is involved in DNA damage repair
physiological function
-
Esa1 mediates increased H4 acetylation and enhanced chromatin remodeling complex RSC occupancy and histone eviction in coding sequences and stimulates the rate of transcription elongation by polymerase II
physiological function
-
role for Rtt109 and H3K56 acetylation in maintaining repetitive DNA sequences in Saccharomyces cerevisiae
physiological function
-
Rtt109 is important for repairing replication-associated lesions and has functions in addition to maintaining genome stability
physiological function
-
Sas2 is required for subtelomeric reporter transgene silencing, but also for transcriptional activity of transgenes integrated into rDNA, for transcriptional activation of a mutated HMRE silent mating type locus and for protection of euchromatin from heterochromatin spreading
physiological function
-
the SAGA complex contains the histone ubiquitin protease Ubp8 and the histone acetyltransferase Gcn5 and is responsible for efficient transcription of SAGA regulated genes such as GAL1 and ADH2
physiological function
MYST protein acetyltransferase activity requires active site lysine autoacetylation
physiological function
-
transcriptional coactivytor gcn5 gene replacement mutants show a mild growth deficiency. Gcn5 is required for adaptation to stresses mediated by KCl and CaCl2, calcoflour white, MnCl2 and caffeine. The histone acetyltransferase activity of Gcn5 is required for its role in stress response. Gcn5-dependent KCl response genes include membrane transporter VMR1 and heat-shock-response gene SSA4. The FLO8 gene, which encodes a transcriptional regulator, is up-regulated in the mutant. During KCl stress adaptation, Gcn5 shows a tendency for redistribution from short genes to the transcribed regions of long genes
physiological function
-
in Saccharomyces cerevisiae the lysine-acetyltransferase Gcn5 (KAT2) is part of the SAGA complex and is responsible for histone acetylation widely or at specific lysines. In wild-type mitochondria the Gcn5 protein is present in the mitoplasts, suggesting a distinct mitochondrial function for Gcn5 independent from the SAGA complex and possibly another function for this protein connecting epigenetics and metabolism, role of Gcn5 as a factor involved in respiratory metabolism, overview
physiological function
lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts
physiological function
lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. Rtt109 has a low catalytic efficiency in isolation, but it is much more active when associated with the histone chaperones Asf1 and Vps75. The two chaperones also determine substrate specificity, with the preferred substrate being H3K56 when Rtt109 is associated with Asf1, whereas H3K9 and H3K23 are acetylated when in complex with Vps75
physiological function
the lysine acetyltransferase complex NuA4 plays a role in phospholipid homeostasis. One role for NuA4 is the regulation of chromatin remodeling and gene transcription through the acetylation of histones H4 andH2A-Z, and NuA4 also targets nonhistone proteins
physiological function
the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule (SG) formation upon glucose deprivation but not heat stress. The impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels via the acetyl-CoA carboxylase Acc1. Both NuA4 and the metabolite acetyl-CoA are critical signaling pathways regulating the formation of glucose-deprived stress granules. Functionally redundant roles for Eaf7 and Gcn5 in SG formation upon glucose deprivation, overview. NuA4 is required for glucose deprivation stress granule formation but does not impact processing bodies. NuA4 does not regulate the formation of stress granules through the inhibition of translation initiation or the Snf1 pathway. Eaf1 and Eaf7 are not required for the inhibition of translation initiation upon 10 minutes glucose deprivation
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis. Tertiary structure analysis of Rtt109 with bound acetyl-CoA (PDB ID 3qm0)
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis. Tertiary structure analysis of Rtt109 with bound acetyl-CoA (PDB ID 3qm0)
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis. Tertiary structure analysis of Rtt109 with bound acetyl-CoA (PDB ID 3qm0)
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis. Tertiary structure analysis of Rtt109 with bound acetyl-CoA (PDB ID 3qm0)
additional information
mechanism of action and structural analysis of KATs, detailed overview. All KATs are characterized by a similar tertiary structure in the central core. This structure consists of an alpha/beta fold, which is important for co-substrate binding and catalysis. Tertiary structure analysis of Rtt109 with bound acetyl-CoA (PDB ID 3qm0)
additional information
NuA4 is a 13-subunit KAT complex containing the essential catalytic domain Esa1 and held together by the scaffolding protein Eaf1
additional information
-
NuA4 is a 13-subunit KAT complex containing the essential catalytic domain Esa1 and held together by the scaffolding protein Eaf1
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
-
1 * 44000 + 1 * 75000 + 1 * 29000, the SAS complex consists of Sas2, Sas4 and Sas5, mass spectrometry analysis
43000
-
x * 43000, recombinant Ada2/Ada3/Gcn5-enzyme complex, SDS-PAGE, x * 43200, recombinant Piccolo NuA4-enzyme complex, SDS-PAGE
43200
-
x * 43000, recombinant Ada2/Ada3/Gcn5-enzyme complex, SDS-PAGE, x * 43200, recombinant Piccolo NuA4-enzyme complex, SDS-PAGE
44000
-
1 * 44000 + 1 * 75000 + 1 * 29000, the SAS complex consists of Sas2, Sas4 and Sas5, mass spectrometry analysis
75000
-
1 * 44000 + 1 * 75000 + 1 * 29000, the SAS complex consists of Sas2, Sas4 and Sas5, mass spectrometry analysis
additional information
additional information
-
three-dimensional structure of the ternary complex of tGcn5 domain
additional information
-
three-dimensional structure of the ternary complex of tGcn5 domain
additional information
-
enzyme is part of a bridging complex, containing Ada2 and Ada3, for gene activation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 43000, recombinant Ada2/Ada3/Gcn5-enzyme complex, SDS-PAGE, x * 43200, recombinant Piccolo NuA4-enzyme complex, SDS-PAGE
multimer
the NuA4 histone acetyltransferase complex is composed of at least ACT1, ARP4, EAF3, EAF5, EAF6, EAF7, EPL1, ESA1, SWC4, TRA1, VID21, YAF9 and YNG2 subunits
trimer
additional information
trimer
-
1 * 44000 + 1 * 75000 + 1 * 29000, the SAS complex consists of Sas2, Sas4 and Sas5, mass spectrometry analysis
trimer
-
heterotrimeric HAT-B complex in which Hat2 bridges Hat1 and Hif1 proteins
additional information
-
ability of HATs to form distinct multi-subunit complexes. The SAGA complex contains the histone ubiquitin protease Ubp8 and the histone acetyltransferase Gcn5
additional information
isoform Rtt109 and histone chaperone Vps75 form a stable complex with nanomolar binding affinity
additional information
NuA4 is a multi-subunit complex, composed of the essential catalytic subunit Esa1, five other essential subunits Act1, Arp4, Epl1, Swc4, Tra1, and seven non-essential subunits Eaf1, Eaf3, Eaf5, Eaf6, Eaf7, Yaf9, and Yng2. Molecular and structural dissection has revealed NuA4 to be modular in nature, assembly of its multiple sub-complexes depends on the Eaf1 subunit
additional information
-
NuA4 is a multi-subunit complex, composed of the essential catalytic subunit Esa1, five other essential subunits Act1, Arp4, Epl1, Swc4, Tra1, and seven non-essential subunits Eaf1, Eaf3, Eaf5, Eaf6, Eaf7, Yaf9, and Yng2. Molecular and structural dissection has revealed NuA4 to be modular in nature, assembly of its multiple sub-complexes depends on the Eaf1 subunit
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
acetyltransferase activity requires active site lysine autoacetylation at a conserved lysine K262
additional information
-
acetyltransferase activity requires active site lysine autoacetylation at a conserved lysine K262
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallization of the catalytic domains of Gcn5 and p/CAF with a number of peptide substrates including sequences from histone and p53
-
molecular model of the complex between enzyme Rtt109 and histone chaperone Vps75 based on X-ray diffraction of crystals. The model reveals distinct negative electrostatic surfaces on an Rtt109 molecule that interface with complementary electropositive ends of a symmetrical Vps75 dimer. Rtt109 variants with interface point substitutions lack the ability to be fully activated by Vps75, yet these variants show no adverse effect on Asf1-dependent Rtt109 activities in vitro and in vivo. Molecular model with a 1:2 complex of Rtt109-Vps75 which acetylates a heterodimer of H3-H4
-
the X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A190S
-
site-directed mutagenesis, mutant of Gcn5, similar kinetics to wild-type
A190T
-
site-directed mutagenesis, mutant of Gcn5, decreased Km for acetyl-CoA
C303A
-
site-directed mutagenesis of Sas3, exchange in zinc finger motif, remaining activity: 4.5% of wild-type activity
C304A
site-directed mutagenesis, the mutant shows activity and pH-dependence similar to the wild-type enzyme
C304S
C304S/E338Q
-
site-directed mutagenesis, the mutant protein is intrinsically unstable and catalytically inactive, the mutant cell is lethal
C306A
-
site-directed mutagenesis of Sas3, exchange in zinc finger motif, remaining activity: 11.1% of wild-type activity
C323A
-
site-directed mutagenesis of Sas3, exchange in zinc finger motif, no remaining activity
D287A/D288A
mutation does not substantially change the shape of the kcat-pH profile, suggesting these conserved residues do not function as base catalysts for histone acetylation
D287N
mutation does not substantially change the shape of the kcat-pH profile, suggesting these conserved residues do not function as base catalysts for histone acetylation
D288N
mutation does not substantially change the shape of the kcat-pH profile, suggesting these conserved residues do not function as base catalysts for histone acetylation. Mutant reveals a dramatic 1000fold decrease in kcat/Km for acetyl-CoA
D343V
-
site-directed mutagenesis, the mutant shows reduced histone H4 acetylation compared to the wild-type Esa1
E173Q
-
site-directed mutagenesis, 500-600 decrease in turnover, no effect on substrate binding, Glu173 is the general base catalyst
E299K/E300K/D301K
-
similar activity toward H3 in comparison to wild-type enzyme, more than 10fold reduction in activation by chaperone Vps75
E338Q
E374A/E378A
-
similar activity toward H3 in comparison to wild-type enzyme
E374K/E378K
-
similar activity toward H3 in comparison to wild-type enzyme, more than 10fold reduction in activation by chaperone Vps75
G429E
-
site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, no remaining activity
G431A
-
site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, nearly no remaining activity: 0.8% of wild-type activity
H319A
-
site-directed mutagenesis of Sas3, exchange in zinc finger motif, nearly no remaining activity: 1.2% of wild-type activity
K262R
mutant does not support growth of yeast cells, mutant is catalytically inactive
K428A
-
site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 55.9% of wild-type activity
K56Q
-
mutation of the acetylation site of histone H3, the mutant shows CAG repeat contractions similar to the wild-type enzyme
K56R
-
mutation of the acetylation site of histone H3, regulation of H3K56 acetylation plays a role in preventing CAG repeat contractions, but may not account for the full effect of deleting the RTT109 gene
L254P
-
esa1 mutant (reduced histone H4 acetylation) at 36°C (restrictive temperature) is sensitive to 6-azauracil (inhibitor impeding elongation by lowering nucleotide pools) but shows little effect at 30°C (permissive temperature), gene length dependent defects in transcription
L357H
-
site-directed mutagenesis, the mutant shows 41% reduced histone H4 acetylation compared to the wild-type Esa1
Q426A
-
site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 38.6% of wild-type activity
W66R
-
site-directed mutagenesis, the mutant shows reduced histone H4 acetylation compared to the wild-type Esa1
Y430A
-
site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 16.7% of wild-type activity
Y430L
-
site-directed mutagenesis of Sas3, exchange in acetyl-CoA binding motif, remaining activity: 87.0% of wild-type activity
additional information
C304S
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
C304S
-
site-directed mutagenesis, the mutant shows 97.4% reduced histone H4 acetylation at pH 8.0 compared to the wild-type Esa1
E338Q
site-directed mutagenesis, the mutant shows 200fold reduced kcat at pH 7.5 compared to the wild-type enzyme
E338Q
-
site-directed mutagenesis, the mutant shows 99.5% reduced histone H4 acetylation at pH 8.0 compared to the wild-type Esa1, recombinant Esa1-E338Q displays detectable HATactivity at elevated pH of 9.2
additional information
-
temperature sensitive Esa1 mutant strain shows reduced activity in vitro and needs histone H4 acetylated at Lys5 as substrate in vivo
additional information
-
comparison of enzyme activity and cell growth in wild-type and hat1-deficient cells, overview
additional information
-
deletion of either ASF1 or RTT109 in cycling cells ablates H3-K56 acetylation and leads to elevated levels of DNA damage-associated gammaH2A and Rad53 phopshorylation
additional information
-
double mutant esa1/gcn5 at 36°C is very sensitive to 6-azauracil (inhibitor impeding elongation by lowering nucleotide pools) and shows littler but still strong effect at 30°C (permissive temperature), gene length dependent defects in transcription
additional information
-
effects of sas2 mutation in yeast are quite specific to the euchromatin/heterochromatin boundary
additional information
-
gcn5 deletion mutant (reduced H3 acetylation) at 36°C (restrictive temperature) is very sensitive to 6-azauracil (inhibitor impeding elongation by lowering nucleotide pools) but shows less effect at 30°C (permissive temperature), gene length dependent defects in transcription
additional information
-
mutant cells lacking RTT109 have a high level of CAG/CTG repeat contractions and a twofold increase in breakage at CAG/CTG repeats. Dnl4 and Rad51-dependent pathways do play a role in creating some of the repeat contractions in rtt109-deficient cells
additional information
wild-type, mutants of core stress-granule (SG) subunits pbp1DELTA and pub1DELTA, along with NuA4 non-essential mutants eaf1DELTA and eaf7DELTA, are transformed with a Pab1-GFP expressing plasmid. None of the mutants examined display a significant increase or constitutive formation of SGs under glucose conditions compared to wild-type. Upon glucose deprivation (GD), Pab1-GFP SGs are induced in wild-type cells but the induction is significantly reduced in pub1DELTA and pbp1DELTA cells. Upon glucose deprivation eaf1DELTA and eaf7DELTA cells show a decrease in Pab1-GFP SGs to a similar extent as pbp1DELTA and pub1DELTA cells. Decreases in GD-SG formation are seen for NuA4 mutants' eaf3DELTA and eaf5DELTA. Furthermore, while the temperature-sensitive allele of ESA1, esa1-L254P (esa1-ts) form GD-SGs at the permissive temperature (25°C), when pre-incubated at the non-permissive temperature (37°C) prior to 10 minutes of glucose deprivation, there is a significant decrease in Pab1-GFP foci formation, indicating that the catalytic activity of NuA4 is required for Pab1-GFP SG formation. While gcn5DELTA cells do not display a significant reduction in GD-SG assembly compared to wild-type cells using the endogenously integrated Pab1-GFP, eaf7DELTAgcn5DELTA cells display a significant reduction in GD-SG formation at 10 minutes compared to both wild-type and single KAT mutants
additional information
-
wild-type, mutants of core stress-granule (SG) subunits pbp1DELTA and pub1DELTA, along with NuA4 non-essential mutants eaf1DELTA and eaf7DELTA, are transformed with a Pab1-GFP expressing plasmid. None of the mutants examined display a significant increase or constitutive formation of SGs under glucose conditions compared to wild-type. Upon glucose deprivation (GD), Pab1-GFP SGs are induced in wild-type cells but the induction is significantly reduced in pub1DELTA and pbp1DELTA cells. Upon glucose deprivation eaf1DELTA and eaf7DELTA cells show a decrease in Pab1-GFP SGs to a similar extent as pbp1DELTA and pub1DELTA cells. Decreases in GD-SG formation are seen for NuA4 mutants' eaf3DELTA and eaf5DELTA. Furthermore, while the temperature-sensitive allele of ESA1, esa1-L254P (esa1-ts) form GD-SGs at the permissive temperature (25°C), when pre-incubated at the non-permissive temperature (37°C) prior to 10 minutes of glucose deprivation, there is a significant decrease in Pab1-GFP foci formation, indicating that the catalytic activity of NuA4 is required for Pab1-GFP SG formation. While gcn5DELTA cells do not display a significant reduction in GD-SG assembly compared to wild-type cells using the endogenously integrated Pab1-GFP, eaf7DELTAgcn5DELTA cells display a significant reduction in GD-SG formation at 10 minutes compared to both wild-type and single KAT mutants
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 10
-
irreversible loss of activity below pH 6.0 and above pH 10.0
487068
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native SAS complex and recombinant SAS complex, the latter with Sas2 protein being His-tagged
-
recombinant His-tagged enzyme in Ada2/Ada3/Gcn5 subcomplex of SAGA or in the Piccolo NuA4 complex from Escherichia coli strain BL21(DE3) by metal affinity chromatography followed by anion or cation exchange chromatography, and hydrophobicinteraction chromatography, method development, overview
-
recombinant wild-type Sas3 protein and mutants as GST-fusion proteins from E. coli
-
using talon metal affinity chromatography, anion-exchange chromatography and cation-exchange chromatography. Typical yields of the yeast Ada2/Ada3/Gcn5 complex are approximately 0.5-0.8 mg/L of culture
-
using talon metal affinity chromatography, anion-exchange chromatography, cation-exchange chromatography and hydrophobic interaction chromatography. Typical yields of the Piccolo NuA4 complex are of the 1-3 mg per liter of culture
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli of SAS complex, consisting of Sas2, Sas4, and Sas5, Sas2 is His-tagged, coexpression
-
expression of Gcn5 and mutants thereof in Escherichia coli BL21 (DE3)
-
expression of Gcn5 protein catalytic domain in Escherichia coli BL21 (DE3)
-
expression of His6-tagged wild-type and mutant Esa1s in Escherichia coli strain BL21(DE3)
-
expression of the His-tagged enzyme bound in the Ada2/Ada3/Gcn5 subcomplex of SAGA or the Piccolo NuA4 complex in Escherichia coli strain BL21(DE3), polycistronic vector, method development, overview
-
expression of wild-type Sas3 protein and mutants as GST-fusion proteins in Escherichia coli
-
gene hat1, expression of HA-tagged Hat1, HAT-tagged Hat2 and Myc-tagged Hif1 in yeast cells
-
overexpression of enzyme domain, yGcn5 consists of amino acid residues 99-262
-
successful expression using Escherichia coli BL-21 by using a His-tagged Ada3 subunit of the yeast Ada2/Ada3/Gcn5 complex
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
methods for the analysis of histone acetyltransferase activity in vitro
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TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lopez-Rodas, G.; Perez-Ortin, J.E.; Tordera, V.; Salvador, M.L.; Franco, L.
Partial purification and properties of two histone acetyltransferases from the yeast, Saccharomyces cerevisiae
Arch. Biochem. Biophys.
239
184-190
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Saccharomyces cerevisiae
Travis, G.H.; Colavito-Shepanski, M.; Grunstein, M.
Extensive purification and characterization of chromatin-bound histone acetyltransferase from Saccharomyces cerevisiae
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Saccharomyces cerevisiae
Berger, S.L.
Gene activation by histone and factor acetyltransferases
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11
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Saccharomyces cerevisiae, Homo sapiens, Tetrahymena sp., Homo sapiens GCN5
Takechi, S.; Nakayama, T.
Sas3 is a histone acetyltransferase and requires a zinc finger motif
Biochem. Biophys. Res. Commun.
266
405-410
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Saccharomyces cerevisiae
Clarke, A.S.; Lowell, J.E.; Jacobson, S.J.; Pillus, L.
Esa1p is an essential histone acetyltransferase required for cell cycle progression
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19
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Saccharomyces cerevisiae
Ohba, R.; Steger, D.J.; Brownell, J.E.; Mizzen, C.A.; Cook, R.G.; Cote, J.; Workman, J.L.; Allis, C.D.
A novel H2A/H4 nucleosomal histone acetyltransferase in Tetrahymena thermophila
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Saccharomyces cerevisiae, Tetrahymena thermophila
Tanner, K.G.; Langer, M.R.; Kim, Y.; Denu, J.M.
Kinetic mechanism of the histone acetyltransferase GCN5 from yeast
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275
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Saccharomyces cerevisiae
Trievel, R.C.; Li, F.Y.; Marmorstein, R.
Application of a fluorescent histone acetyltransferase assay to probe the substrate specificity of the human p300/CBP-associated factor
Anal. Biochem.
287
319-328
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Saccharomyces cerevisiae, Homo sapiens, Tetrahymena thermophila, Homo sapiens GCN5, Tetrahymena thermophila GCN5
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Mutational analysis of conserved residues in the GCN5 family of histone acetyltransferases
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31321-31331
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Saccharomyces cerevisiae
Hasan, S.; Hottiger, M.O.
Histone acetyl transferases: a role in DNA repair and DNA replication
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80
463-474
2002
Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus, Tetrahymena thermophila, Homo sapiens GCN5
Langer, M.R.; Fry, C.J.; Peterson, C.L.; Denu, J.M.
Modulating acetyl-CoA binding in the GCN5 family of histone acetyltransferases
J. Biol. Chem.
277
27337-27344
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Saccharomyces cerevisiae, Homo sapiens, Tetrahymena thermophila, Homo sapiens GCN5, Tetrahymena thermophila GCN5
Sutton, A.; Shia, W.J.; Band, D.; Kaufman, P.D.; Osada, S.; Workman, J.L.; Sternglanz, R.
Sas4 and Sas5 are required for the histone acetyltransferase activity of Sas2 in the SAS complex
J. Biol. Chem.
278
16887-16892
2003
Saccharomyces cerevisiae
Sklenar, A.R.; Parthun, M.R.
Characterization of yeast histone H3-specific type B histone acetyltransferases identifies an ADA2-independent Gcn5p activity
BMC Biochem.
5
11
2004
Saccharomyces cerevisiae
Song, O.k.; Wang, X.; Waterborg, J.H.; Sternglanz, R.
An Nalpha-acetyltransferase responsible for acetylation of the N-terminal residues of histones H4 and H2A
J. Biol. Chem.
278
38109-38112
2003
Saccharomyces cerevisiae (Q04751)
Poveda, A.; Pamblanco, M.; Tafrov, S.; Tordera, V.; Sternglanz, R.; Sendra, R.
Hif1 is a component of yeast histone acetyltransferase B, a complex mainly localized in the nucleus
J. Biol. Chem.
279
16033-16043
2004
Saccharomyces cerevisiae
Shia, W.J.; Osada, S.; Florens, L.; Swanson, S.K.; Washburn, M.P.; Workman, J.L.
Characterization of the yeast trimeric-SAS acetyltransferase complex
J. Biol. Chem.
280
11987-11994
2005
Saccharomyces cerevisiae
Benson, L.J.; Annunziato, A.T.
In vitro analysis of histone acetyltransferase activity
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33
45-52
2004
Saccharomyces cerevisiae, Homo sapiens
Le Masson, I.; Yu, D.Y.; Jensen, K.; Chevalier, A.; Courbeyrette, R.; Boulard, Y.; Smith, M.M.; Mann, C.
Yaf9, a novel NuA4 histone acetyltransferase subunit, is required for the cellular response to spindle stress in yeast
Mol. Cell. Biol.
23
6086-6102
2003
Saccharomyces cerevisiae (P53930), Saccharomyces cerevisiae
Carrozza, M.J.; Utley, R.T.; Workman, J.L.; Cote, J.
The diverse functions of histone acetyltransferase complexes
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19
321-329
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Saccharomyces cerevisiae, Homo sapiens
Berndsen, C.E.; Albaugh, B.N.; Tan, S.; Denu, J.M.
Catalytic mechanism of a MYST family histone acetyltransferase
Biochemistry
46
623-629
2007
Saccharomyces cerevisiae (Q08649)
Mai, A.; Rotili, D.; Tarantino, D.; Ornaghi, P.; Tosi, F.; Vicidomini, C.; Sbardella, G.; Nebbioso, A.; Miceli, M.; Altucci, L.; Filetici, P.
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49
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2006
Saccharomyces cerevisiae, Homo sapiens
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Expression and purification of recombinant yeast Ada2/Ada3/Gcn5 and Piccolo NuA4 histone acetyltransferase complexes
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41
271-277
2007
Saccharomyces cerevisiae
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Recruitment of the type B histone acetyltransferase Hat1p to chromatin is linked to DNA double-strand breaks
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26
3649-3658
2006
Saccharomyces cerevisiae
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MYST family histone acetyltransferases take center stage in stem cells and development
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31
1050-1061
2009
Arabidopsis thaliana, Danio rerio, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Danio rerio zMoz
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Catalysis and substrate selection by histone/protein lysine acetyltransferases
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18
682-689
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Saccharomyces cerevisiae, Homo sapiens, Tetrahymena sp., Tetrahymena sp. GCN5
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The Rtt109 histone acetyltransferase facilitates error-free replication to prevent CAG/CTG repeat contractions
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9
414-420
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Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4705
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Site specificity of yeast histone acetyltransferase B complex in vivo
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275
2122-2136
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Saccharomyces cerevisiae
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178
1209-1220
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Saccharomyces cerevisiae
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Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109
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28
4342-4353
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Saccharomyces cerevisiae
Ginsburg, D.S.; Govind, C.K.; Hinnebusch, A.G.
NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5
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29
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Saccharomyces cerevisiae
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49
6375-6385
2010
Saccharomyces cerevisiae (Q07794)
Arnold, K.M.; Lee, S.; Denu, J.M.
Processing mechanism and substrate selectivity of the core NuA4 histone acetyltransferase complex
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50
727-737
2011
Saccharomyces cerevisiae
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21
4976-4979
2011
Saccharomyces cerevisiae
Xue-Franzen, Y.; Johnsson, A.; Brodin, D.; Henriksson, J.; Buerglin, T.R.; Wright, A.P.
Genome-wide characterisation of the Gcn5 histone acetyltransferase in budding yeast during stress adaptation reveals evolutionarily conserved and diverged roles
BMC Genomics
11
200
2010
Saccharomyces cerevisiae, Lachancea kluyveri
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
Homo sapiens, Saccharomyces cerevisiae (Q08649), Saccharomyces cerevisiae
Kolonko, E.M.; Albaugh, B.N.; Lindner, S.E.; Chen, Y.; Satyshur, K.A.; Arnold, K.M.; Kaufman, P.D.; Keck, J.L.; Denu, J.M.
Catalytic activation of histone acetyltransferase Rtt109 by a histone chaperone
Proc. Natl. Acad. Sci. USA
107
20275-20280
2010
Saccharomyces cerevisiae
Secci, D.; Carradori, S.; Bizzarri, B.; Bolasco, A.; Ballario, P.; Patramani, Z.; Fragapane, P.; Vernarecci, S.; Canzonetta, C.; Filetici, P.
Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors
Bioorg. Med. Chem.
22
1680-1689
2014
Saccharomyces cerevisiae, Homo sapiens
Ouyang, C.; Mu, J.; Lu, Q.; Li, J.; Zhu, H.; Wang, Q.; Zou, M.H.; Xie, Z.
Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/alpha-tubulin acetylation
Autophagy
2019
1-18
2019
Saccharomyces cerevisiae, Homo sapiens (Q92830), Homo sapiens, Saccharomyces cerevisiae D273-10B/A1, Saccharomyces cerevisiae W303-1A
Fiorentino, F.; Mai, A.; Rotili, D.
Lysine acetyltransferase inhibitors structure-activity relationships and potential therapeutic implications
Future Med. Chem.
10
1067-1091
2018
Drosophila melanogaster (O02193), Drosophila melanogaster (P51123), Drosophila melanogaster (Q960X4), Homo sapiens (O15516), Homo sapiens (O95251), Homo sapiens (P21675), Homo sapiens (Q15788), Homo sapiens (Q8WYB5), Homo sapiens (Q92793), Homo sapiens (Q92794), Homo sapiens (Q92830), Homo sapiens (Q92831), Homo sapiens (Q92993), Homo sapiens (Q9BQG0), Homo sapiens (Q9H7Z6), Homo sapiens (Q9H9T3), Homo sapiens (Q9UKN8), Homo sapiens (Q9Y6Q9), Homo sapiens, Saccharomyces cerevisiae (P39979), Saccharomyces cerevisiae (P46677), Saccharomyces cerevisiae (P53114), Saccharomyces cerevisiae (Q06592), Saccharomyces cerevisiae (Q07794), Saccharomyces cerevisiae ATCC 204508 (P39979), Saccharomyces cerevisiae ATCC 204508 (P46677), Saccharomyces cerevisiae ATCC 204508 (P53114), Saccharomyces cerevisiae ATCC 204508 (Q06592), Saccharomyces cerevisiae ATCC 204508 (Q07794)
Dacquay, L.; Flint, A.; Butcher, J.; Salem, D.; Kennedy, M.; Kaern, M.; Stintzi, A.; Baetz, K.
NuA4 lysine acetyltransferase complex contributes to phospholipid homeostasis in Saccharomyces cerevisiae
G3 (Bethesda)
7
1799-1809
2017
Saccharomyces cerevisiae (Q08649), Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741 (Q08649)
Rollins, M.; Huard, S.; Morettin, A.; Takuski, J.; Pham, T.T.; Fullerton, M.D.; Cote, J.; Baetz, K.
Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae
PLoS Genet.
13
e1006626
2017
Saccharomyces cerevisiae (Q08649), Saccharomyces cerevisiae, Homo sapiens (Q92993), Homo sapiens, Saccharomyces cerevisiae BY4741 (Q08649)
EXTERNAL LINKS (specific for EC-Number 2.3.1.48)
Transporter Classification Database (TCDB): 1.I.1.1.3
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