Information on EC 2.3.1.48 - histone acetyltransferase and Organism(s) Homo sapiens and UniProt Accession O14929

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Homo sapiens
UNIPROT: O14929


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.3.1.48
-
RECOMMENDED NAME
GeneOntology No.
histone acetyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N6-acetyl-L-lysine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
9054-51-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + histone H4 peptide
CoA + acetylpeptide of histone H4
show the reaction diagram
residues 1-20 of histone H4
-
-
?
acetyl-CoA + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
show the reaction diagram
acetyl-CoA + histone
CoA + acetylhistone
show the reaction diagram
acetyl-CoA + histone H1
CoA + acetylhistone H1
show the reaction diagram
acetyl-CoA + histone H2A
CoA + acetylhistone H2A
show the reaction diagram
acetyl-CoA + histone H2B
CoA + acetylhistone H2B
show the reaction diagram
acetyl-CoA + histone H3
CoA + acetylhistone
show the reaction diagram
-
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
show the reaction diagram
acetyl-CoA + histone H3 N-terminal tail
CoA + acetylated histone H3 N-terminal tail
show the reaction diagram
-
50 mM Tris-HCl, pH 8.0, 30C
-
-
?
acetyl-CoA + histone H3 peptide
CoA + acetylhistone H3 peptide
show the reaction diagram
acetyl-CoA + histone H3 peptide
CoA + actylhistone H3
show the reaction diagram
-
residues 1-21 of human histone H3
-
-
-
acetyl-CoA + histone H4
CoA + acetylhistone H4
show the reaction diagram
acetyl-CoA + histone H4
peptide CoA + acetylhistone H4 peptide
show the reaction diagram
-
specific acetylation of Lys16
-
-
?
acetyl-CoA + histone H4 peptide
CoA + acetylhistone H4 peptide
show the reaction diagram
-
a synthetic peptide corresponding to the first 20 amino acids of the histone H4 N-terminus
-
-
?
acetyl-CoA + histone H4 peptide
CoA + actylhistone H4
show the reaction diagram
-
residues 2-24 of human histone H4
-
-
-
acetyl-CoA + p50 protein
CoA + acetyl-p50 protein
show the reaction diagram
acetyl-CoA + p53
CoA + acetyl-p53
show the reaction diagram
acetyl-CoA + p65 protein
CoA + acetyl-p65 protein
show the reaction diagram
acetyl-CoA + protein p53
CoA + acetylprotein p53
show the reaction diagram
acetyl-CoA + transcription factor TFIIE
CoA + acetylated transcription factor TFIIE
show the reaction diagram
-
substrate is a basal transcription factor
-
-
?
acetyl-CoA + transcription factor TFIIF
CoA + acetylated transcription factor TFIIF
show the reaction diagram
-
substrate is a basal transcription factor
-
-
?
alpha-tubulin + acetyl-CoA
acetyl-alpha-tubulin + CoA
show the reaction diagram
-
-
-
-
?
androgen receptor + acetyl-CoA
acetylated androgen receptor + CoA
show the reaction diagram
ATM kinase + acetyl-CoA
acetylated ATM kinase + CoA
show the reaction diagram
H4 peptide + acetyl-CoA
?
show the reaction diagram
-
-
-
-
?
histone + acetyl-CoA
acetyl-histone + CoA
show the reaction diagram
histone H3 + acetyl-CoA
acetyl-histone H3 + CoA
show the reaction diagram
histone H4 + acetyl-CoA
acetyl-histone H4 + CoA
show the reaction diagram
promyelotic leukemia zinc finger gene + acetyl-CoA
acetylated promyelotic leukemia zinc finger gene + CoA
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
show the reaction diagram
-
-
-
-
?
acetyl-CoA + histone
CoA + acetylhistone
show the reaction diagram
acetyl-CoA + histone H2A
CoA + acetylhistone H2A
show the reaction diagram
-
acetylation at Lys5 by Tip60
-
-
?
acetyl-CoA + histone H3
CoA + acetylhistone H3
show the reaction diagram
acetyl-CoA + histone H4
CoA + acetylhistone H4
show the reaction diagram
acetyl-CoA + p50 protein
CoA + acetyl-p50 protein
show the reaction diagram
-
acetylation of p50 by p300 independent of shear stress
-
-
?
acetyl-CoA + p53
CoA + acetyl-p53
show the reaction diagram
Q9H7Z6
p53 protein-acetylation of the Lys120 residue
-
-
?
acetyl-CoA + p65 protein
CoA + acetyl-p65 protein
show the reaction diagram
-
acetylation of p65 by p300 during translocation into the nuclei in response to shear stress
-
-
?
androgen receptor + acetyl-CoA
acetylated androgen receptor + CoA
show the reaction diagram
-
receptor signaling in prostate cancer cells is augmented by the androgen receptor coactivator p300, which transactivates and acetylates the androgen receptor in the presence of 100 nM dihydrotestosterone, involvement of p300 in neuropeptide activation of androgen receptor signaling, overview
-
-
?
ATM kinase + acetyl-CoA
acetylated ATM kinase + CoA
show the reaction diagram
-
ATM protein kinase regulates the cells response to DNA damage through the phosphorylation of proteins involved in cell-cycle checkpoints and DNA repair, suppression of Tip60 blocks the activation of ATMs kinase activity, ATM autophosphorylation e.g. at Ser1981, and prevents the ATM-dependent phosphorylation of p53 and chk2, inactivation of Tip60 sensitizes cells to ionizing radiation, overview
-
-
?
histone + acetyl-CoA
acetyl-histone + CoA
show the reaction diagram
histone H3 + acetyl-CoA
acetyl-histone H3 + CoA
show the reaction diagram
histone H4 + acetyl-CoA
acetyl-histone H4 + CoA
show the reaction diagram
-
-
-
-
?
promyelotic leukemia zinc finger gene + acetyl-CoA
acetylated promyelotic leukemia zinc finger gene + CoA
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetyl-CoA
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2R,3S)-4-methylidene-5-oxo-2-propyltetrahydrofuran-3-carboxylic acid
-
i.e. butyrolactone MB-3, a GCN5 inhibitor
(4E)-2-(4-acetylphenyl)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-5-methyl-2,4-dihydro-3H-pyrazol-3-one
-
-
1,7-bis(3-bromo-4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
-
-
1-(4-(3-nitrophenyl)thiazol-2-yl)-2-(propan-2-ylidene)hydrazine
-
-
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
2,5-diphenylisothiazol-3(2H)-one
-
-
2,6-bis(3-bromo-4-hydroxybenzylidene)cyclohexanone
-
-
2-(2-cyclopentylidenehydrazinyl)-4-(3-methoxyphenyl)-1,3-thiazole
-
-
2-(2-cyclopentylidenehydrazinyl)-4-(3-nitrophenyl)-1,3-thiazole
-
-
2-(2-cyclopentylidenehydrazinyl)-4-(4-fluorophenyl)-1,3-thiazole
-
-
2-(2-cyclopentylidenehydrazinyl)-4-(4-methoxyphenyl)-1,3-thiazole
-
-
2-(2-cyclopentylidenehydrazinyl)-4-phenyl-1,3-thiazole
-
-
2-(2-pyridyl)-isothiazol-3(2H)-one
-
-
2-(3-chloro-4-fluorophenyl)isothiazol-3(2H)-one
-
-
2-(3-methoxyphenyl)isothiazolo[5,4-b]pyridin-3(2H)-one
-
antiproliferative effects in cancer cells, GI50 value 0.007 mM with SK-N-SH cell
2-(3-pyridyl)-isothiazol-3(2H)-one
-
-
2-(4-(trifluoromethyl)benzyl)isothiazolo[5,4-b]pyridin-3(2H)-one
-
antiproliferative effects in cancer cells, GI50 value 0.0005 mM with SK-N-SH cell, 0.030 mM with MCF-7 cell
2-(4-dimethylaminoaniline)-isothiazol-3(2H)-one
-
-
2-(4-fluorophenyl)isothiazolo[5,4-b]pyridin-3(2H)-one
-
antiproliferative effects in cancer cells, GI50 value 0.010 mM with SK-N-SH cell, 0.037 mM with MCF-7 cell
2-(4-methylphenyl)isothiazolo[5,4-b]pyridin-3(2H)-one
-
antiproliferative effects in cancer cells, GI50 value 0.006 mM with SK-N-SH cell
2-(4-morpholinoaniline)-isothiazol-3(2H)-one
-
-
2-(4-pyridyl)-isothiazol-3(2H)-one
-
-
2-(heptylsulfanyl)-1-(2-hydroxyphenyl)ethan-1-one
-
-
2-(phenyl)-isothiazolo[5,4-b]pyridin-3(2H)-one
-
-
2-butyl-6-hydroxybenzoic acid
-
-
2-decyl-4-hydroxyquinoline-3-carboxylic acid
-
-
2-decyl-6-hydroxybenzoic acid
2-dodecylmalonate
-
compound induces hyperacetylation of specific lysine residues of histone H3, in particular residues K9 and K18, and raises the level of pan-acetylated H4. Compound inhibits the acetylation of all the other H3 and H4 lysines, with the exception of residue K8Ac of histone H4
2-ethylisothiazol-3(2H)-one
-
-
2-hydroxy-5-pentadecylbenzoic acid
2-hydroxy-5-pentylbenzoic acid
-
-
2-hydroxy-6-(11-hydroxyundecyl)benzoic acid
-
-
2-hydroxy-6-(5-hydroxypentyl)benzoic acid
-
-
2-hydroxy-6-pentadecylbenzoic acid
2-pentylisothiazol-3(2H)-one
-
-
2-phenyl-5-(trityloxymethyl)isothiazol-3(2H)-one
-
-
2-phenylisothiazol-3(2H)-one
-
-
2-tert-butyl-5-(dodecylthio)isothiazol-3(2H)-one-1-oxide
-
-
2-tert-butyl-5-chloroisothiazol-3(2H)-one 1-oxide
-
-
2-tridecylmalonate
-
inhibition of the acetylation of histone H3 residuesK9/K18, being practically inactive in all the other assays
2-undecylmalonate
-
compound exhibits a significant inhibition of the acetylation of almost any lysine residue explored, with the sole exception of residue K8 of H4. Compound reduces the level of K5Ac of H4 and, more markedly, K16Ac of H4
2-[(1E)-1-[2-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hydrazinylidene]ethyl]pyridine
-
-
3-(Z)-(benzylsulfanyl)propenoic acid
-
-
3-(Z)-(benzylsulfinyl)-2-N-(4-dimethylaminoanilino)-propenamide
-
-
3-(Z)-(benzylsulfinyl)-2-N-(4-morpholinoanilino)-propenamide
-
-
3-(Z)-(benzylsulfinyl)-N-(2-pyridyl)propenamide
-
-
3-(Z)-(benzylsulfinyl)-N-(3-pyridyl)propenamide
-
-
3-(Z)-(benzylsulfinyl)-N-(4-pyridyl)propenamide
-
-
3-pentadecylidenepentane-2,4-dione
-
inhibition of the acetylation of histone H3 residuesK9/K14, being practically inactive in all the other assays
3-quinolinecarboxylic acid ethyl ester
-
effects in vivo, overview
3-Z-benzylsulfanyl-4-trityloxy-but-2-enoic acid phenylamide
-
-
3-Z-benzylsulfinyl-4-trityloxy-but-2-enoic acid phenylamide
-
-
3-[(1E)-1-[2-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hydrazinylidene]ethyl]-2H-1-benzopyran-2-one
-
-
3-[(E)-[2-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]hydrazinylidene]methyl]-2,3-dihydro-1H-indole
-
-
3-[2-[(2Z)-2-(3-methylcyclopentylidene)hydrazinyl]-1,3-thiazol-4-yl]-2H-1-benzopyran-2-one
-
-
3-[2-[2-(propan-2-ylidene)hydrazinyl]-1,3-thiazol-4-yl]-2H-1-benzopyran-2-one
-
-
4,5-dichloro-2-ethylisothiazol-3(2H)-one
-
-
4,5-dichloro-2-ethylisothiazol-3(2H)-one-1-oxide
-
-
4-(4-bromophenyl)-2-[2-(propan-2-ylidene)hydrazinyl]-1,3-thiazole
-
-
4-(4-chlorophenyl)-2-[(2E)-2-[1-(1,3-thiazol-2-yl)ethylidene]hydrazinyl]-1,3-thiazole
-
-
4-(4-chlorophenyl)-2-[2-(propan-2-ylidene)hydrazinyl]-1,3-thiazole
-
-
4-azidomethyl-2-phenyl-isothiazol-3(2H)-one
-
-
4-bromomethyl-2-phenylisothiazol-3(2H)-one
-
-
4-hydroxy-2-methylquinoline-3-carboxylic acid
-
-
4-hydroxy-2-pentadecylquinoline-3-carboxylic acid
-
-
4-hydroxy-2-pentylquinoline-3-carboxylate
-
effects in vivo, overview, in vitro clear reduction of the acetylation extents of both histone H3 and alpha-tubulin at 0.1 mM
4-hydroxy-2-pentylquinoline-3-carboxylic acid
-
-
4-methoxymethyl-2-phenyl-isothiazol-3(2H)-one
-
-
4-methyl-2-phenylisothiazol-3(2H)-one
-
-
4-methyl-5-methoxy-2-phenyl-isothiazol-3(2H)-one
-
-
4-trityloxy-but-2-ynoic acid phenylamide
-
-
5-acetoxymethyl-2-phenylisothiazol-3(2H)-one
-
-
5-azidomethyl-2-phenylisothiazol-3(2H)-one
-
-
5-chloro-2-(3-chloro-4-fluorophenyl)isothiazol-3(2H)-one
-
-
5-chloro-2-ethyl-4-methylisothiazol-3(2H)-one
-
-
5-chloro-2-ethyl-4-methylisothiazol-3(2H)-one-1-oxide
-
-
5-chloro-2-ethylisothiazol-3(2H)-one
-
-
5-chloro-2-ethylisothiazol-3(2H)-one-1-oxide
-
-
5-chloro-2-pentylisothiazol-3(2H)-one
-
-
5-chloro-4-methyl-2-phenylisothiazol-3(2H)-one
-
-
5-decyl-2-hydroxybenzoic acid
5-hydroxymethyl-2-phenylisothiazol-3(2H)-one
-
-
5-methyl-2-phenylisothiazol-3(2H)-one
-
-
5-phenylureidomethyl-2-phenylisothiazol-3(2H)-one
-
-
6-(4-chlorophenyl)-2-(2-(3-methylcyclopentylidene)hydrazinyl)pyrimidin-4(3H)-one
-
-
6-(4-chlorophenyl)-2-(2-cyclopentylidenehydrazinyl)pyrimidin-4(3H)-one
-
-
acetylated histone H3 peptide
-
acetylated at Lys14, product inhibition of PCAF protein, noncompetitive against both substrates
-
allspice hot water extract
-
leads to a potent anti-HAT activity since the allspice hot water extract possesses a strong inhibitory effect on p300 and CBP (40% at 0.1 ng/ml). Chromatin immunoprecipitation indicates that the acetylation of histone H3 in the PSA and B2M promoter regions was also repressed
-
anacardic acid
anarcadic acid
-
-
benzyl [2-(5-chloro-3-oxoisothiazol-2(3H)-yl)ethyl]carbamate
-
-
bisubstrate analogue histone H3-peptide-coenzyme A
-
bisubstrate analogue methyl-histone H3-peptide-coenzyme A
-
peptide consisting of 20 and 7 amino acid residues
-
CCT004463
-
in vivo cell proliferation inhibition
CCT004464
-
in vivo cell proliferation inhibition
CCT004465
-
in vivo cell proliferation inhibition
CCT004466
-
in vivo cell proliferation inhibition
CCT004467
-
in vivo cell proliferation inhibition
CCT077791
-
IC50: 0.0022-0.0073 mM, in vivo cell proliferation inhibition, reduces acetylation of histones H3 and H4 and alpha-tubulin in cancer cell lines
CCT077792
-
IC50: 0.0027-0.015 mM, in vivo cell proliferation inhibition
CCT077796
-
IC50: 0.0187-0.0202 mM, in vivo cell proliferation inhibition
CCT079769
-
IC50: 0.0547 mM, in vivo cell proliferation inhibition
chondroitin sulfate
-
-
CoA
-
product inhibition of PCAF protein, competitive against acetyl-CoA
curcumin
desulfo-coenzyme A
-
dead-end inhibitor, noncompetitive versus histone H3-peptide and competitive versus actyl-CoA
diethyl 2-tetradecylidenemalonate
-
compound exhibits a significant inhibition of the acetylation of almost any lysine residue explored, with the sole exception of residue K8 of H4. Compound reduces the level of K5Ac of H4 and, more markedly, K16Ac of H4
DNA
-
acetylation of histone H1by the enzymes PCAF and GNC5 is inhibited in vivo by complexing of H1 with DNA
ethyl 2-decyl-4-hydroxyquinoline-3-carboxylate
-
-
ethyl 2-methylquinoline-3-carboxylate
-
effects in vivo, overview
ethyl 3-(5-chloro-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
ethyl 4-hydroxy-2-methylquinoline-3-carboxylate
-
-
ethyl 4-hydroxy-2-pentadecylquinoline-3-carboxylate
-
-
ethyl 4-hydroxy-2-pentylquinoline-3-carboxylate
-
-
garcinol
geminin
-
a Cdt1 repressor, inhibits HBO1 acetylase activity in a a Cdt1-dependent manner in the context of a Cdt1-HBO1 complex, and it associates with origins and inhibits H4 acetylation and licensing in vivo, but geminin does not block the interaction of Cdt1 with HBO1 in vitro or Cdt1-dependent recruitment of HBO1 to replication origins in vivo
-
H3-CoA-20
H3-CoA-20-Tat
-
IC50: 0.012 mM, recombinant enzyme
-
heparan sulfate proteoglycans
-
heparan sulfate proteoglycans isolated from corneal and pulmonary fibroblasts inhibit HAT activity with similar effectiveness as heparin
-
heparin
-
ability of heparin to inhibit HAT is dependent upon its size and structure: small heparin-derived oligosaccharides (above 8 sugars) and N-desulfated or O-desulfated heparin show reduced inhibitory activity. Heparin is shown to bind to pCAF. Enzyme assays indicate that heparin shows the characteristics of a competitive-like inhibitor causing a 50fold increase in the Km of pCAF for histone H4
histone H3-peptide mutant K14A
-
dead-end inhibitor analogue, mutant histone H3 -peptide consisting of amino acid residues 3-20 K14A
-
hyaluronic acid
-
-
isogarcinol
isothiazolone
Keratan sulfate
-
-
LTK14
Lys-CoA
Lys-CoA-Tat
-
IC50: 250 nM, recombinant enzyme, complete inhibtion of acetylation of the promyelotic leukemia zinc finger gene
MB-3
-
-
methyl 2-(5-chloro-3-oxoisothiazol-2(3H)-yl)ethanoate
-
-
methyl 3-(3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-(4,5-dichloro-1-oxido-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-(4,5-dichloro-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-(5-chloro-1-oxido-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-(5-chloro-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-(5-chloro-3-oxoisothiazol-2(3H)-yl)propanoic acid
-
-
methyl 3-(5-chloro-4-methyl-1-oxido-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-(5-chloro-4-methyl-3-oxoisothiazol-2(3H)-yl)propanoate
-
-
methyl 3-[(5-chloroisothiazol-3-yl)amino]propanoate
-
-
methyl 3-[4-chloro-5-(dodecylthio)-1-oxido-3-oxoisothiazol-2(3H)-yl]propanoate
-
-
methyl 3-[4-{[(benzyloxy)carbonyl]amino}-5-chloro-3-oxoisothiazol-2(3H)-yl]propanoate
-
-
methyl 3-[5-(dodecylthio)-1-oxido-3-oxoisothiazol-2(3H)-yl] propanoate
-
-
methyl 4-(3-oxoisothiazol-2(3H)-yl)butanoate
-
-
methyl 4-(5-chloro-3-oxoisothiazol-2(3H)-yl)butanoate
-
-
methyl 5-(5-chloro-3-oxoisothiazol-2(3H)-yl)pentanoate
-
-
methyl 6-(5-chloro-3-oxoisothiazol-2(3H)-yl)hexanoate
-
-
montelukast
-
decreases HAT activity by attenuating the activating effect of TNF-alpha
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-decyl-6-ethoxybenzamide
-
inhibits human p300 recombinant enzyme similar to anacardic acid
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-ethoxy-6-octylbenzamide
-
inhibits human p300 recombinant enzyme similar to anacardic acid, moreover this inhibitor induces significant apoptosis at 0.05 nM in U937 leukemia cells
Plumbagin
siRNA
-
silencing of enzyme gene
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-chloro-4-trifluoromethyl benzamide
-
activates the enzyme, the relative position of the -CF3 and -Cl is crucial for p300 HAT activity enhancement, overview
2-dodecylmalonate
-
compound induces hyperacetylation of specific lysine residues of histone H3, in particular residues K9 and K18, and raises the level of pan-acetylated H4. Compound inhibits the acetylation of all the other H3 and H4 lysines, with the exception of residue K8Ac of histone H4
4-chloro-2-trifluoromethyl benzamide
-
activates the enzyme, the relative position of the -CF3 and -Cl is crucial for p300 HAT activity enhancement, overview
bleomycin
-
activation of the ATM-associated enzyme by bleomycin, the free, non-ATM-associated, Tip60 activity is not activated by bleomycin
CDT1
-
licensing factor Cdt1 stabilizes HBO1 at origins. HBO1 directly interacts with Cdt1, and it enhances Cdt1-dependent rereplication
-
diethyl 2-pentadecylidenemalonate
-
compound induces hyperacetylation of specific lysine residues of histone H3, in particular residues K9 and K18, and raises the level of pan-acetylated H4
E2F1
the transcription factor associates with and recruits GCN5 to sites of DNA damage. E2F1 is required for the GCN5-mediated regulation of lung cancer cell growth and for theG1/S transition. Cyclin D1 and cyclin E1 are downstream targets of E2F1. GCN5 is enriched at the E2F1-binding site of the cyclin D1, cyclin E1, or E2F1 promoters
-
laminar shear stress
-
laminar shear stress stimulates acetylation of histones 3 and 4 at the region of the eNOS promoter SSRE and extends 3' toward the eNOS coding region. Laminar shear stress induces p300 binding to p65 and leads to increase of p300 histone acetyltransferase activity by 2.5fold and to increase of acetylation of p65, but not of p50 acetylation, overview
-
membrane transporter
-
for acetyl-CoA and acetyltransferase from cytosol into lumen of the ER/ER Golgi intermediate compartment
-
TNF-alpha
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0067
acetyl-CoA
wild-type, pH not specified in the publication, temperature not specified in the publication
0.0208 - 0.197
histone H4 peptide
-
0.00027 - 0.046
acetyl-CoA
0.039 - 0.7
histone H3
-
0.05
histone H3-peptide
-
PCAF catalytic domain
-
1.12
histone H3-peptide p19
-
PCAF catalytic domain
-
0.75
histone H3-peptide p27
-
PCAF catalytic domain
-
0.0000053 - 0.5
histone H4
1.28 - 4.63
protein p53
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.14
acetyl-CoA
wild-type, pH not specified in the publication, temperature not specified in the publication
0.15 - 4.28
histone H4 peptide
-
0.0033 - 0.0467
acetyl-CoA
0.18 - 0.22
histone H3
-
0.0117 - 0.0667
histone H3-peptide
-
0.131
histone H3-peptide p19
-
PCAF catalytic domain
-
0.00317 - 0.0583
histone H3-peptide p20
-
0.17
histone H3-peptide p27
-
PCAF catalytic domain
-
0.0018 - 0.0062
histone H4
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
619
acetyl-CoA
wild-type, pH not specified in the publication, temperature not specified in the publication
1.41 - 205
histone H4 peptide
-
2.73 - 9.73
histone H3
-
0.036 - 0.068
protein p53
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0198
2,5-diphenylisothiazol-3(2H)-one
-
PCAF
0.019 - 0.028
2-(2-pyridyl)-isothiazol-3(2H)-one
0.0065 - 0.0144
2-(3-pyridyl)-isothiazol-3(2H)-one
0.0054
2-(4-dimethylaminoaniline)-isothiazol-3(2H)-one
-
PCAF
0.0075 - 0.0099
2-(4-morpholinoaniline)-isothiazol-3(2H)-one
0.0015 - 0.003
2-(4-pyridyl)-isothiazol-3(2H)-one
0.037
2-decyl-6-hydroxybenzoic acid
-
pH and temperature not specified in the publication
0.079
2-hydroxy-5-pentadecylbenzoic acid
-
pH and temperature not specified in the publication
0.157
2-hydroxy-6-(11-hydroxyundecyl)benzoic acid
-
pH and temperature not specified in the publication
0.064
2-hydroxy-6-pentadecylbenzoic acid
-
pH and temperature not specified in the publication
0.023 - 0.028
2-phenylisothiazol-3(2H)-one
0.0427
4-azidomethyl-2-phenyl-isothiazol-3(2H)-one
-
PCAF
0.102
4-methoxymethyl-2-phenyl-isothiazol-3(2H)-one
-
PCAF
0.032
4-methyl-2-phenylisothiazol-3(2H)-one
-
PCAF
0.2
4-methyl-5-methoxy-2-phenyl-isothiazol-3(2H)-one
-
above, PCAF
0.162
5-acetoxymethyl-2-phenylisothiazol-3(2H)-one
-
PCAF
0.058
5-azidomethyl-2-phenylisothiazol-3(2H)-one
-
PCAF
0.2
5-chloro-4-methyl-2-phenylisothiazol-3(2H)-one
-
above, PCAF
0.057
5-decyl-2-hydroxybenzoic acid
-
pH and temperature not specified in the publication
0.109
5-hydroxymethyl-2-phenylisothiazol-3(2H)-one
-
PCAF
0.2
5-methyl-2-phenylisothiazol-3(2H)-one
-
above, PCAF
0.2
5-phenylureidomethyl-2-phenylisothiazol-3(2H)-one
-
above, PCAF
0.00066
acetylated histone H3 peptide
-
PCAF catalytic domain
-
0.00044
coenzyme A
-
PCAF catalytic domain
0.0049
garcinol
-
-
0.0039
isogarcinol
-
-
0.0051
LTK14
-
-
0.00002
Lys-CoA
-
inhibition of peptide acetylation
additional information
additional information
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.32
(4E)-2-(4-acetylphenyl)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]-5-methyl-2,4-dihydro-3H-pyrazol-3-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.005
1,7-bis(3-bromo-4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
Homo sapiens;
-
-
0.033
2,6-bis(3-bromo-4-hydroxybenzylidene)cyclohexanone
Homo sapiens;
-
-
0.00503
2-(3-methoxyphenyl)isothiazolo[5,4-b]pyridin-3(2H)-one
Homo sapiens;
-
substrate histone H3 peptide, pH 7.5, 30C
0.0255 - 0.13
2-(4-(trifluoromethyl)benzyl)isothiazolo[5,4-b]pyridin-3(2H)-one
0.00072 - 0.00164
2-(4-fluorophenyl)isothiazolo[5,4-b]pyridin-3(2H)-one
0.00463
2-(4-methylphenyl)isothiazolo[5,4-b]pyridin-3(2H)-one
Homo sapiens;
-
substrate histone H3 peptide, pH 7.5, 30C
0.01
2-tert-butyl-5-(dodecylthio)isothiazol-3(2H)-one-1-oxide
Homo sapiens;
-
above
0.01
2-tert-butyl-5-chloroisothiazol-3(2H)-one 1-oxide
Homo sapiens;
-
above
0.0024
4,5-dichloro-2-ethylisothiazol-3(2H)-one
Homo sapiens;
-
-
0.01
4,5-dichloro-2-ethylisothiazol-3(2H)-one-1-oxide
Homo sapiens;
-
above
0.01
5-chloro-2-ethyl-4-methylisothiazol-3(2H)-one
Homo sapiens;
-
above
0.01
5-chloro-2-ethyl-4-methylisothiazol-3(2H)-one-1-oxide
Homo sapiens;
-
above
0.003
5-chloro-2-ethylisothiazol-3(2H)-one
Homo sapiens;
-
-
0.01
5-chloro-2-ethylisothiazol-3(2H)-one-1-oxide
Homo sapiens;
-
above
0.0022 - 0.0073
CCT077791
Homo sapiens;
-
IC50: 0.0022-0.0073 mM, in vivo cell proliferation inhibition, reduces acetylation of histones H3 and H4 and alpha-tubulin in cancer cell lines
0.0027 - 0.015
CCT077792
Homo sapiens;
-
IC50: 0.0027-0.015 mM, in vivo cell proliferation inhibition
0.0187 - 0.0202
CCT077796
Homo sapiens;
-
IC50: 0.0187-0.0202 mM, in vivo cell proliferation inhibition
0.0547
CCT079769
Homo sapiens;
-
IC50: 0.0547 mM, in vivo cell proliferation inhibition
0.4
curcumin
Homo sapiens;
-
value above 0.4
0.034 - 0.064
H3-CoA-20
Homo sapiens;
-
IC50: 0.034-0.064 mM
0.012
H3-CoA-20-Tat
Homo sapiens;
-
IC50: 0.012 mM, recombinant enzyme
-
0.0001 - 0.03
Lys-CoA
0.00025
Lys-CoA-Tat
Homo sapiens;
-
IC50: 250 nM, recombinant enzyme, complete inhibtion of acetylation of the promyelotic leukemia zinc finger gene
0.01
methyl 3-(4,5-dichloro-1-oxido-3-oxoisothiazol-2(3H)-yl)propanoate
Homo sapiens;
-
above
0.0026
methyl 3-(4,5-dichloro-3-oxoisothiazol-2(3H)-yl)propanoate
Homo sapiens;
-
-
0.0056
methyl 3-(5-chloro-1-oxido-3-oxoisothiazol-2(3H)-yl)propanoate
Homo sapiens;
-
-
0.0018
methyl 3-(5-chloro-3-oxoisothiazol-2(3H)-yl)propanoate
Homo sapiens;
-
-
0.01
methyl 3-(5-chloro-4-methyl-1-oxido-3-oxoisothiazol-2(3H)-yl)propanoate
Homo sapiens;
-
above
0.01
methyl 3-(5-chloro-4-methyl-3-oxoisothiazol-2(3H)-yl)propanoate
Homo sapiens;
-
above
0.01
methyl 3-[4-chloro-5-(dodecylthio)-1-oxido-3-oxoisothiazol-2(3H)-yl]propanoate
Homo sapiens;
-
above
0.01
methyl 3-[5-(dodecylthio)-1-oxido-3-oxoisothiazol-2(3H)-yl] propanoate
Homo sapiens;
-
above
0.002 - 0.02
Plumbagin
additional information
additional information
Homo sapiens;
-
10, 25, 50 microM inhibit FLAG-tagged recombinant PCAF in vitro with an IC50 beyond 50 microM with purified human HeLa core histone as substrate; Hep-G2 hepatocarcinoma cells: with 5 microM plumbagin 50% reduction of histone H3 acetylation, with 25 microM 90% reduction, significant overall acetylation status of histones, prominent reduction in H3 and H4, immunofluorescence analysis (anti-acetylated histone H3 polyclonal antibodies) of HeLa cells (treated with deacetylase inhibitors to induce histone acetylation) confirm the inhibitory effect of plumbagin with 5 microM inhibitor, with 25 microM almost complete reduction in acetylation level
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
7.6
-
assay at
7.9
assay at
additional information
-
reaction kinetic is pH-dependent
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 9.5
-
PCAF protein
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22 - 37
-
assay at
37
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
HBO1
Manually annotated by BRENDA team
-
from brain tumor
Manually annotated by BRENDA team
high expression evel of CBP/p300 in hepatocarcinoma tissue
Manually annotated by BRENDA team
-
P300/CBP-associated factor expression level analysis
Manually annotated by BRENDA team
-
colon tumor cell line
Manually annotated by BRENDA team
-
human embryonic kidney A293 cells
Manually annotated by BRENDA team
leukemic
Manually annotated by BRENDA team
-
from neuronal tissue
Manually annotated by BRENDA team
high GCN5 expression level which correlates with tumor size
Manually annotated by BRENDA team
-
neuroblastoma
Manually annotated by BRENDA team
-
HBO1
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
catalytic site facing the lumen of the endoplasmic reticulum/endoplasmic reticulum Goli intermediate compartment (ER/ERGIC)
Manually annotated by BRENDA team
-
catalytic site facing the lumen of the endoplasmic reticulum/endoplasmic reticulum Goli intermediate compartment (ER/ERGIC)
Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
O14929
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20000
-
SDS-PAGE, rough estimation from figure
28000
-
SDS-PAGE
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with acetyl coenzyme A and histone H4 peptide, i.e. residues 1-20, to 1.9 A resolution. The cofactor and the side chain of lysine 12 of histone H4 peptide are placed in the canyon between the central and C-terminal domains. Histone H4 peptide adopts a well-defined conformation and establishes an extensive set of interactions with the enzyme including invariant residues Glu64 and Trp199, which together govern substrate-binding specificity. There is a cumulative effect of the active-site residues Glu187, Glu276, and Asp277 on deprotonation of the epsilon-amino group of reactive Lys12 for direct attack of the acetyl group of the cofactor
modeling of the initial complex between acetyltransferase Gcn5, acetyl-CoA and histone H3 and 20 ns molecular dynamics simulation. Glu80 acts as the general base for deprotonation of residue Lys171 from H3. Glu80, water180 and Lys171 form a proton-wire for the deprotonation process of Lys171. Both loop alpha7-beta7 and loop alpha1-alpha2 play a critical role in binding substrate H3
-
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
-
visualization of multifunctional transcription activator p300 by atomic force microscopy. p300 is almost prolate ellipsoidal in shape, having several bulges. The functionally significant N-terminal and C-terminal regions are located near one end and centre of the molecule, respectively. The presence of N- and C-terminal regions near the central portion of the prolate ellipsoid suggests that all four domain could exist spatially close near the central portion of the molecule and hence capable of binding all four domains simultaneously. The complex between p300 and tumor suppressor protein p53 is elongated in shape. p53 binds at the central region of p300
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA stabilizes the enzyme form PCAF
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cells are lysed after centrifugation in 100 mM Tris-HCl buffer, pH 7.6, immunoprecipitation, affinity purification with ProFound c-Myc-Tag IP/Co-IP kit, subcellular fractionation of homogenized cells in 10 mM triethanolamine, 10 mM acetic acid, 250 mM sucrose, 1 mM EDTA, and 1 mM dithiothreitol, pH 7.4, centrifuged, membrane pellet resuspended in 5% Nycodenz and layered on top of a Nycodenz solution gradient in 10 mM HEPES, pH 7.4, fractions collected and further concentrated by ultracentrifugation
-
recombinant Atac2 fused to two HA and two FLAG tags from nuclear extracts of HEK-293 cells and murine C2C12 cells by M2-agarose affinity chromatography and gel filtration
recombinant catalytic domain of PCAF protein from E. coli
-
recombinant enzyme domains of PCAF and Gcn5
-
recombinant from Sf9 insect cells via baculovirus infection, FLAG-tagged MORF protein
recombinant GST- and FLAG-tagged KAT6B histone acetyltransferase domain from Escherichia coli by affinity chromatography
recombinant GST-tagged enzyme from Escherichia coli by glutathione affinity chromatography
-
recombinant His-tagged catalytic domain of PCAF protein from E. coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression of isoform a in Escherichia coli
ATAC2, DNA and amino acid sequence determination and analysis, Atac2 fused to two HA and two FLAG tags is stably expressed in nuclei of HEK-293 cells and in murine C2C12 cells
expressed in Escherichia coli
-
expression in HEK-293 cell
-
expression of full-length MORF and PCAF proteins in Sf9 cells
-
expression of His6-tagged enzyme in Spodoptora frugiperda Sf21 cell using the baculovirus infection system
-
expression of MORF protein as FLAG-tagged protein in Sf9 insect cells via baculovirus infection, and as Gal4-fusion protein in 293T cells, amino acid sequence
expression of mutant HATG485. Coexpression of HBO1 and Jade-1
-
expression of the catalytic domain of PCAF protein, amino acid residues 493-658, in Escherichia coli BL21 (DE3)
-
expression of the GST-tagged enzyme in Escherichia coli
-
expression of wild-type and inactive mutant Tip60 in HeLa cells and 293T cells
-
expression of wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus expression system, genetic regulation of enzyme expression, overview
-
gene GCN5, recombinant expression in HEK-293T cells
gene KAT6B, genotyping in small cell lung cancer cell lines, recombinant expression of GST- and FLAG-tagged KAT6B histone acetyltransferase domain in Escherichia coli
in vitro transcription and translation of p300 by rabbit reticulocyte extracts, transient expression of an enzyme-GAL4 reporter gene construct in 293T cells, in HeLa cells, and in KG1 cells
-
MYST1, sequence comparison, phylogenetic tree
-
overexpression of enzyme domain PCAF amino acid residues 493-658 in Escherichia coli
-
overexpression of recombinant histone acetyltransferase domain of p300/CBP-associated factor, residues 157657, in Escherichia coli
-
PCR-amplification, stable transfection of CHO cells, with myc-tag, overexpressing enzyme
-
real-time RT-PCR analysis
-
recombinant p300 is expressed in baculovirus, and K1358A HAT mutant gene is expressed in Escherichia coli BL21; recombinant PCAF expressed in baculovirus
-
stable overexpression of FLAG-tagged MOF-conbtaining complex subunits in HEK293/FRT or HeLa S3 cells, overview
T7-coupled in vitro transcription and translation of FLAG-tagged enzyme
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
although downregulation of UHRF1 by RNA interference enhances Tip60 expression, a significant decrease of the level of acetylated H2AK5 is observed
-
down-regulation of p300 by siRNA prevents UV-induced matrix metalloproteinase MMP-1 expression and inhibits UV-enhanced phosphorylation of H2AX, p53 level, and acetyl-H3
-
down-regulation of Tip60 and DNMT1 by RNA interference, dramatically reduced the levels of acetylated H2AK5
-
downregulation by RNA interference decreases the MYST1 content in human cells and results in lowered Lys16 acetylation in histone H4
-
transfected cells increase acetyltransferase activity 2fold, and by the treatment with the lipid second messenger ceramide; transfected cells increase acetyltransferase activity 3fold, and by the treatment with the lipid second messenger ceramide
-
UV irradiation of cultured human dermal fibroblasts induces matrix metalloproteinase MMP-1 expression and increases the level of phosphorylation of H2AX, p53 and the acetylation of histone H3
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D277N
strong decrease in catalytic efficiency
D62A
4fold increase in Km value
E187Q
strong decrease in catalytic efficiency
E276Q
strong decrease in catalytic efficiency
E64A
6fold increase in Km value
W199A
3fold increase in Km value
C746A
-
site-directed mutagenesis, mutation in the HAT domain, leads to only slightly reduced catalytic activity, but highly reduced cyclin D1 transcription in the cells
D551G/V582A/D639E
-
random and site-directed mutagenesis
D639V
-
random mutagenesis
E611K
-
random mutagenesis
E649D
-
random mutagenesis
E742Q
-
site-directed mutagenesis, mutation in the HAT domain, leads to only slightly reduced catalytic activity, but highly reduced cyclin D1 transcription in the cells
F605L
-
random mutagenesis
G485
-
a HBO1 mutant, which contains a mutation of an invariant glycine in the histone acetyltransferase domain that abolishes enzymatic activity
G923/925D
-
site-directed mutagenesis, mutation in the HAT domain, leads to only slightly reduced catalytic activity, but highly reduced cyclin D1 transcription in the cells
H524Q
-
random mutagenesis
H592R
-
random mutagenesis
H600R
-
random mutagenesis
I511T/M529I
-
random and site-directed mutagenesis
K1358A
-
site directed mutagenesis of lysine 1358 of the p300 acetyltransferase domain reveals that inhibitor binds via a hydrogen bond to this lysine residue in the wild-type, in the mutant no binding leads to total loss of acetyltransferase activity
K274R
-
mutant is catalytically inactive
K542E/D601G/Y612C
-
random and site-directed mutagenesis
K542E/D639E
-
random and site-directed mutagenesis
K627R/D639E
-
random and site-directed mutagenesis
L503P/D601G
-
random and site-directed mutagenesis
L503P/D601G/Y612C
-
random and site-directed mutagenesis
N504I/Q519L/V572A/V582A
-
random and site-directed mutagenesis
P655R
-
random mutagenesis
Q519R
-
random mutagenesis
S1834A
-
site-directed mutagenesis, the mutant shows no histone acetylation and ICAM-1 gene expression, overview
S1834E
-
site-directed mutagenesis, the mutant shows no histone acetylation and ICAM-1 gene expression, overview
T535A/D551G
-
random and site-directed mutagenesis
V582A
-
random mutagenesis
V582A/D639E
-
random and site-directed mutagenesis
V582A/Y612C
-
random and site-directed mutagenesis
V582D
-
random mutagenesis
V582D/D639V
-
random and site-directed mutagenesis
Y1467F
-
the mutant shows a 150fold reduction in catalytic activity relative to wild-type enzyme
Y612C
-
random mutagenesis
Y612C/P655R
-
random and site-directed mutagenesis
Y638A
-
mutant of PCAF catalytic domain, increased Km and decreased kcat compared to wild-type
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
methods for the analysis of histone acetyltransferase activity in vitro
medicine