Information on EC 2.3.1.32 - lysine N-acetyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Archaea, Bacteria

EC NUMBER
COMMENTARY hide
2.3.1.32
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RECOMMENDED NAME
GeneOntology No.
lysine N-acetyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
acetyl phosphate + L-lysine = phosphate + N6-acetyl-L-lysine
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acyl group transfer
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Lysine degradation
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lysine metabolism
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SYSTEMATIC NAME
IUBMB Comments
acetyl-phosphate:L-lysine N6-acetyltransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
37257-12-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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)
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 phosphate + L-lysine
phosphate + N6-acetyl-L-lysine
show the reaction diagram
-
-
-
?
acetyl phosphate + L-ornithine
phosphate + N5-acetyl-L-ornithine
show the reaction diagram
-
best substrate
-
?
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 + acetyl-histone
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, 30°C
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-
?
acetyl-CoA + L-Lys
?
show the reaction diagram
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-
-
-
?
acetyl-CoA + L-lysine
CoA + N6-acetyl-L-lysine
show the reaction diagram
-
-
-
-
?
Acs (AMP forming) + L-Lys
?
show the reaction diagram
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-
-
-
?
septin protein + acetyl-CoA
?
show the reaction diagram
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TAP-tagged septin proteins are cleaved from the magnetic beads during the KAT assay. Multiple sites of acetylation on four of the five yeast mitotic septins, Cdc3, Cdc10, Cdc12 and Shs1 are discovered. In addition to acetylating itself, NuA4 is capable of acetylating Cdc3, Cdc12 and Shs1 in vitro, acetylation on Cdc10 is not detected
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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 phosphate + L-lysine
phosphate + N6-acetyl-L-lysine
show the reaction diagram
-
-
-
?
acetyl phosphate + L-ornithine
phosphate + N5-acetyl-L-ornithine
show the reaction diagram
-
best substrate
-
?
acetyl-CoA + beta-site amyloid precursor protein-cleaving enzyme 1
CoA + acetylated beta-site amyloid precursor protein-cleaving enzyme 1
show the reaction diagram
Q9UHF3
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-
-
?
acetyl-CoA + histone
CoA + acetyl-histone
show the reaction diagram
acetyl-CoA + L-lysine
CoA + N6-acetyl-L-lysine
show the reaction diagram
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-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
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slight stimulation
Mg2+
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slight stimulation
additional information
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no activation by Zn2+, Mn2+, Co2+, Ni2+, Fe3+ or acetate
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
anacardic acid
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%
phosphate
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above 0.1 mM
Plumbagin
siRNA
silencing of enzyme gene
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
histone chaperone
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Rtt109 associates with chaperone Vps75 (H3K9 and H3K23 acetylation in vivo) or Asf1 (H3K56 acetylation in vivo), stimulation of catalytic activity by chaperones, R55109 stimulates histone deposition by the chaperones, the complex of enzyme + chaperone alters substrate specificity, targets to specific loci, enhances acetyltransferase activity, restricts access of non-target proteins, and coordinates the multiple enzyme activities of the complex
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membrane transporter
for acetyl-CoA and acetyltransferase from cytosol into lumen of the ER/ER Golgi intermediate compartment
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methylated histone
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stimulates interaction of NuA4 complex with histone
NuA4
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cooperation with the NuA4 complex to enhance its functions but independent contribution to acetylation
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piccolo NuA4 complex
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accessory proteins to support the function of Esa1, stimulating the catalytic activity of the enzyme
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SAGA
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cooperation with the Gcn5 complex to enhance its functions but independent contribution to acetylation
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SAGA complex
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histone ubiquitin protease Ubp8 and histone acetyltransferase Gcn5 form a complex
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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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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.35 - 12.4
acetyl phosphate
0.0003 - 0.04
acetyl-CoA
0.132
Acs (AMP forming)
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pH 7.0, 37°C
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0.075 - 1.4
histone
4.24
L-lysine
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1.32
L-ornithine
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.3
acetyl-CoA
Salmonella enterica
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K0.5, pH 7.0, 37°C
8
Acs (AMP forming)
Salmonella enterica
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pH 7.0, 37°C
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0.0017 - 1.7
histone
4.1
histone peptide
Saccharomyces cerevisiae
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p300
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
60
Acs (AMP forming)
Salmonella enterica
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pH 7.0, 37°C
42171
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.002 - 0.02
Plumbagin
additional information
additional information
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.43
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
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assay at
8.6
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various buffer systems
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.3 - 9.2
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about half-maximal activity at pH 8.3, about 70% of maximal activity at pH 9.2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
38
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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p53 modulation assay
Manually annotated by BRENDA team
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liver cancer cell line, histones are hyperacetylated in hepatocarcinomas
Manually annotated by BRENDA team
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novel taste learning elicited biphasic (acute and long-tasting) activation of two distinct lysine acetyltransferase activities along with the EPK/MAPK cascade in insular cortex
Manually annotated by BRENDA team
neuroblastoma
Manually annotated by BRENDA team
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
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20000
SDS-PAGE, rough estimation from figure
28000
SDS-PAGE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0°C, 5 h
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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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described elsewhere
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed as a His-tagged fusion protein
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nuclear enzyme overexpression in HEK-293 cells
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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; recombinant PCAF expressed in baculovirus
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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
an enrichment of TgGCN5-A at the upstream regions of genes activated by alkaline pH exposure is detected
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expression of the abl operon is strictly salt dependent. Expression of ablA and ablB at the standard NaCl concentration of 38.5 mM is not detectable, but it increases drastically with increasing salt concentrations in the growth medium. The level of transcription of the abl operon is identical in cells grown with 400 or 800 mM NaCl
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
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
L254P
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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
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
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