Page last updated: 2024-10-24

histone H4K5 acetyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: acetyl-CoA + histone H4 L-lysine (position 5) = CoA + histone H4 N6-acetyl-L-lysine (position 5). [EC:2.3.1.48]

Histone H4K5 acetyltransferase activity refers to the enzymatic ability of certain proteins to catalyze the transfer of an acetyl group from acetyl coenzyme A (acetyl-CoA) to the epsilon-amino group of lysine 5 (K5) on histone H4. This modification is a key component of epigenetic regulation, influencing gene expression and other cellular processes.

Here's a detailed explanation of the molecular function:

1. **Substrate Recognition:** The acetyltransferase recognizes and binds to histone H4, specifically targeting the lysine 5 residue. This interaction involves specific amino acid sequences and electrostatic interactions that create a binding pocket for the histone.

2. **Acetyl-CoA Binding:** The acetyltransferase binds to acetyl-CoA, the donor molecule carrying the acetyl group. The enzyme's active site contains a cysteine residue that forms a thioester bond with the acetyl group, preparing it for transfer.

3. **Catalysis:** Through a complex series of steps, the acetyltransferase facilitates the transfer of the acetyl group from acetyl-CoA to the lysine 5 residue on histone H4. This involves nucleophilic attack by the epsilon-amino group of lysine 5 on the acetyl group, releasing CoA and forming an acetylated lysine residue.

4. **Product Release:** After acetylation, the enzyme releases the modified histone H4, allowing it to interact with other proteins or DNA.

**Significance of H4K5 Acetylation:**

* **Gene Regulation:** Acetylation of histone H4 at lysine 5 is associated with increased gene expression. It typically alters chromatin structure, making DNA more accessible to transcription factors and promoting transcription initiation.
* **Chromatin Remodeling:** This modification can influence the recruitment of other proteins involved in chromatin remodeling, such as ATP-dependent chromatin remodelers. These proteins can reposition nucleosomes, altering the accessibility of DNA and regulating gene expression.
* **Cellular Processes:** H4K5 acetylation is implicated in various cellular processes, including development, cell cycle regulation, and response to stress. It plays a role in maintaining genomic stability, DNA repair, and cell differentiation.

**Note:** Specific acetyltransferases responsible for H4K5 acetylation and their regulatory mechanisms are being actively investigated, and the exact roles of this modification in different cellular contexts continue to be explored.'
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Proteins (5)

ProteinDefinitionTaxonomy
Bromodomain and PHD finger-containing protein 3A bromodomain and PHD finger-containing protein 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9ULD4]Homo sapiens (human)
Histone acetyltransferase KAT8A histone acetyltransferase KAT8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H7Z6]Homo sapiens (human)
Histone acetyltransferase KAT8A histone acetyltransferase KAT8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H7Z6]Homo sapiens (human)
PeregrinA peregrin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P55201]Homo sapiens (human)
Bromodomain-containing protein 1A bromodomain-containing protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95696]Homo sapiens (human)

Compounds (18)

CompoundDefinitionClassesRoles
4-aminophenol4-aminophenol : An amino phenol (one of the three possible isomers) which has the single amino substituent located para to the phenolic -OH group.

4-aminophenol: RN given refers to parent cpd
aminophenolallergen;
metabolite
1-nitronaphthalene1-nitronaphthalene : A mononitronaphthalene substituted by a nitro group at position 1.

1-nitronaphthalene: RN given refers to cpd with locant for nitro moiety in 1 position

mononitronaphthalene : A nitronaphthalene carrying a single nitro group at unspecified position.

nitronaphthalene : A nitroarene that is naphthalene substituted by at least one nitro group.
mononitronaphthaleneenvironmental contaminant;
mouse metabolite
phenylhydrazinephenylhydrazinesxenobiotic
4-chloroaniline4-chloroaniline : A chloroaniline in which the chloro atom is para to the aniline amino group.

4-chloroaniline: RN given refers to parent cpd; structure
chloroaniline;
monochlorobenzenes
1-naphthylamine1-naphthylamine : A naphthylamine that is naphthalene substituted by an amino group at position 1.

1-Naphthylamine: A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.

naphthylamine : A primary arylamine that is naphthalene substituted by an amino group at unspecified position.
naphthylaminehuman xenobiotic metabolite
4-fluoroaniline4-fluoroaniline : A primary arylamine that is the derivative of aniline in which the hydrogen at position 4 has been substituted by fluorine. It is used as an intermediate in the manufacture of pharmaceuticals, herbicides and plant growth regulators.

4-fluoroaniline: chemical intermediate manufactured by the Halex process; RN given refers to parent cpd; structure given in first source
fluoroaniline;
primary arylamine
isocarbostyrilisoquinolinone : An isoquinoline containing one or more oxo groups.isoquinolines
ferrocin cN-methyl-2-quinolone: structure in first source
4-phenylpyridinephenylpyridine
tricyclazoletricyclazole : A triazolobenzothiazole that is [1,2,4]triazolo[3,4-b][1,3]benzothiazole which is substituted at position 5 by a methyl group. A fungicide used for the control of rice blast, it is not approved for use within the European Union.

tricyclazole: RN given refers to parent cpd
triazolobenzothiazoleantifungal agrochemical;
melanin synthesis inhibitor
phenylhydrazine hydrochloridephenylhydrazine hydrochloride : A hydrochloride resulting from the reaction of equimolar amounts of phenylhydrazine and hydrogen chloride.hydrochloride
4-fluorobenzylamine
4-hydroxyquinoline4-quinolone : A quinolone that is 1,4-dihydroquinoline substituted by an oxo group at position 4.monohydroxyquinoline;
quinolone
anacardic acidanacardic acid : A hydroxybenzoic acid that is salicylic acid substituted by a pentadecyl group at position 6. It is a major component of cashew nut shell liquid and exhibits an extensive range of bioactivities.

anacardic acid: isolated from Anacardium occidentale; monophenol monooxygenase inhibitor
hydroxy monocarboxylic acid;
hydroxybenzoic acid
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
apoptosis inducer;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
neuroprotective agent;
plant metabolite
2,8-dimercapto-6-hydroxypurine
2-hydroxy-6-[(8Z,11Z)-pentadeca-8,11,14-trien-1-yl]benzoic acidhydroxybenzoic acid
jq1 compoundcarboxylic ester;
organochlorine compound;
tert-butyl ester;
thienotriazolodiazepine
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
bromodomain-containing protein 4 inhibitor;
cardioprotective agent;
ferroptosis inducer
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