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Information on EC 2.3.1.32 - lysine N-acetyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9UHF3
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2.3.1.32 lysine N-acetyltransferaseSpecify your search results
Word Map
- 2.3.1.32
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coactivator
- chromatin
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transactivation
- e1a
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creb-binding
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gnat
- adenovirus
- oncoproteins
- deacetylases
- hdacs
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nucleosomal
- creb
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hypoxia-inducible
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deacetylation
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element-binding
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bromodomains
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p300-mediated
- smads
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hyperacetylation
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acetylase
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trichostatin
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h3k27ac
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corepressors
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non-histone
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p300-dependent
- accoa
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p53-dependent
- myod
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p53-mediated
- tax
- htlv-1
- medicine
- brd4
- pharmacology
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tata-binding
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selangor
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h3k4me1
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
p300/cbp, p/caf, acetyltransferase p300, gcn5-related n-acetyltransferase, p300 acetyltransferase, atase2, atase1, sepat, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetyltransferase, lysine
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lysine acetyltransferase
lysine acetyltransferase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
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SYSTEMATIC NAME
IUBMB Comments
acetyl-phosphate:L-lysine N6-acetyltransferase
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CAS REGISTRY NUMBER
COMMENTARY
37257-12-8
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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 + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
acetyl-CoA + histone H3 N-terminal tail
CoA + acetylated histone H3 N-terminal tail
50 mM Tris-HCl, pH 8.0, 30°C
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-
?
acetyl-CoA + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
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-
-
?
acetyl-CoA + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
50 mM Tris-HCl, pH 8.0, 30°C
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-
?
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
acetyl-CoA + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
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?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
curcumin
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25 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 75%
garcinol
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10 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 80%
isogarcinol
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10 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 70%
LTK14
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20 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 70%
additional information
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no inhibition of p300 by 5-methoxy-2-methyl-1,4-naphthoquinone (RTK2, alkyl substitution of hydroxyl group), 5-ethoxy-2-methyl-1,4-naphthoquinone (RTK3, alkyl substitution of hydroxyl group), 5-isopropoxy-2-methyl-1,4-naphthoquinone (RTK4, alkyl substitution of hydroxyl group), and 5-[2-(dimethylamino)-ethoxy]-2-methyl-1,4-naphthoquinone (RTK10, N,N-dimethylamine substitution of hydroxyl group), less than 10% inhibition with 6-methyl-5,8-dioxo-5,8-dihydronaphthalen-1-yl acetate (RTK5, acetyl substitution of hydroxyl group), 6-methyl-5,8-dioxo-5,8-dihydronaphthalen-1-yl methanesulfonate (RTK6, sulfonyl substitution of hydroxyl group), 2-methyl-5-(2-piperidin-1-ylethoxy)-1,4-naphthoquinone (RTK7, piperidine substitution of hydroxyl group), 2-methyl-5-(2-morpholin-4-ylethoxy)-1,4-naphthoquinone (RTK8, morpholine substitution of hydroxyl group), and ethyl [(6-methyl-5,8-dioxo-5,8-dihydronaphthalen-1-yl)-oxy]acetate (RTK9, ester substitution of hydroxyl group)
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anacardic acid
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10 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 95%
Plumbagin
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RTK1, naturally occurring hydroxynaphthoquinone, isolated from Plumbago rosea roots, inhibits histone acetylation, and induces apoptosis at higher concentrations, it inhibits p300/CBP-mediated acetylation of p53 lysine 373 non-competitively, 25 microM inhibit histidine-tagged recombinant p300 with purified human HeLa core histone as substrate by about 60% compared to control
Plumbagin
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RTK1, naturally occurring hydroxynaphthoquinone, isolated from Plumbago rosea roots, it does not inhibit PCAF acetylation of p53 lysine 320 in vivo in HEK-293 cells (pretreated with acetylation inducer doxorubicin), but 10, 25, and 50 microM inhibit FLAG-tagged recombinant PCAF in vitro (30°C) with purified human HeLa core histone as substrate
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
membrane transporter
for acetyl-CoA and acetyltransferase from cytosol into lumen of the ER/ER Golgi intermediate compartment
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additional information
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the phosphorylation of the receptor-interacting protein 140 (RIP140) by extracellular-signal-related kinase 2 (Erk2) stimulates p300 acetyltransferase to acetylate the RIP140's lysine 158 and lysine 287 residues
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Homo sapiens
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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
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additional information
additional information
Homo sapiens
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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
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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liver cancer cell line, histones are hyperacetylated in hepatocarcinomas
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
catalytic site facing the lumen of the endoplasmic reticulum/endoplasmic reticulum Goli intermediate compartment (ER/ERGIC)
catalytic site facing the lumen of the endoplasmic reticulum/endoplasmic reticulum Goli intermediate compartment (ER/ERGIC)
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is acetylated in seven lysine residues that face the lumen of the ER and ER Golgi intermediate compartment (ERGIC)
malfunction
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dysfunction is associated with diseases like asthma, cardiovascular disorders, diabetes, and cancer
physiological function
physiological function
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specific lysine 158 and lysine 287 acetylation of RIP140 (receptor-interacting protein 140) which is a co-regulator for many transcription factors, acetylation directly enhances the regulator's trans-repressive activity, role in fat accumulation
physiological function
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transcriptional regulation via histone complex acetylation, possibility of longer chain acyl-CoA transfers is proposed for histone acetyltransferases
physiological function
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the acetyltransferases cyclic adenosine monophosphate response element-binding binding protein (CBP) and acetyltransferase p300 attenuate transcriptional activity of the mineralocorticoid receptor through its acetylation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K1358A
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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
additional information
additional information
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Lysine 158 and 287 in the RIP140 (receptor-interacting protein 140) are targets for acetylation by p300 acetyltransferase as shown by site directed mutagenesis of these residues, lysine 158 and 287 replaced by glutamine (mimicking acetylation) turn the RIP140 repressive in the absence of p300, while the alanine replacements (preventing acetylation) prevents responsiveness to p300, the double mutants show stronger effects in the same directions, while lysine 111 and 311 seem not to be targets for the p300 acetyltransferase. Mitogen-activated protein kinase (MAPK) target mutants that mimic (T202E/T207E) or abolish (T202A/T207A) threonine phosphorylation of RIP140 enhance or reduce the stimulation of p300 acetyltransferase, respectively, extracellular-signal-related kinase 2 (Erk2) is identified as the responsible MAPK in this pathway
additional information
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in human embryonic kidney 293 cells, overexpression of cyclic adenosine monophosphate response element-binding binding protein, CBP, or p300, but not p300/CBP-associated factor, increases mineralocorticoid receptor acetylation and decreases expression of mineralocorticoid receptor target genes
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
cells are washed with PBS, harvested in Tris-HCl, pH 7.4, containing 0.5% deoxycholic acid, 150 mM NaCl, 0.1% SDS, 4 mM EDTA, and 1% NP-40, with a protease inhibitor cocktail, 1 mM PMSF, 1 mM sodium fluoride, and 1 mM sodium orthovanadate, centrifugation, supernatant subjected to SDS-PAGE, or for immunoprecipitation lysed cells are collected with 50 mM Tris-HCl, pH 8.0, with 10% glycerol, 100 mM NaCl, 1 mM EDTA, and 0.1% NP-40 with proteinase inhibitor cocktail, 1 mM PMSF, 1 mM sodium fluoride, and 1 mM sodium orthovanadate, incubation with antibodies and G beads, washing, elution of proteins by boiling in 2X Laemmli loading buffer
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
PCR-amplification, stable transfection of CHO cells, with myc-tag, overexpressing enzyme
recombinant p300 is expressed in baculovirus, and K1358A HAT mutant gene is expressed in Escherichia coli BL21
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transfection of COS-1 cells (African green monkey cell line) with plasmids of wild-type enzyme, deficient enzyme or single site mutants fused to reporter genes
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
pathogenesis of late-onset Alzheimer disease, post-translational regulation of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) levels, a membrane protein that acts as the rate-limiting enzyme in the generation of Alzheimer disease amyloid beta-peptide, acetylation protect the protein from degradation
pharmacology
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cyclic adenosine monophosphate response element-binding binding protein and p300 are lysine acetyltransferases responsible for the regulation of mineralocorticoid receptor providing therapeutic targets for the treatment of hypertension
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ho, P.C.; Gupta, P.; Tsui, Y.C.; Ha, S.G.; Huq, M.; Wei, L.N.
Modulation of lysine acetylation-stimulated repressive activity by Erk2-mediated phosphorylation of RIP140 in adipocyte differentiation
Cell. Signal.
20
1911-1919
2008
Homo sapiens
Berndsen, C.E.; Denu, J.M.
Catalysis and substrate selection by histone/protein lysine acetyltransferases
Curr. Opin. Struct. Biol.
18
682-689
2008
Saccharomyces cerevisiae, Homo sapiens
Ravindra, K.C.; Selvi, B.R.; Arif, M.; Reddy, B.A.; Thanuja, G.R.; Agrawal, S.; Pradhan, S.K.; Nagashayana, N.; Dasgupta, D.; Kundu, T.K.
Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin
J. Biol. Chem.
284
24453-24464
2009
Homo sapiens, Mus musculus
Ko, M.H.; Puglielli, L.
Two endoplasmic reticulum (ER)/ER intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels
J. Biol. Chem.
284
2482-2492
2009
Homo sapiens (Q9UHF3)
Seo, M.; Song, M.; Seok, Y.M.; Kang, S.H.; Lee, H.A.; Sohn, U.D.; Kim, I.K.
Lysine acetyltransferases cyclic adenosine monophosphate response element-binding binding protein and acetyltransferase p300 attenuate transcriptional activity of the mineralocorticoid receptor through its acetylation
Clin. Exp. Pharmacol. Physiol.
42
559-566
2015
Homo sapiens
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