histone H3R2 arginine deiminase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: H2O + histone H3 L-arginyl (position 2)= histone H3 L-citrullyl (position 2) + NH4+, resulting in histone H3 citrullination at position 2. [PMID:15339660]

Histone H3R2 arginine deiminase activity refers to the enzymatic ability of certain proteins to catalyze the conversion of arginine residues within the histone H3 protein, specifically at the R2 position, to citrulline. This process, known as citrullination, is a post-translational modification that plays a crucial role in regulating chromatin structure and function.

Histone H3 is a core component of nucleosomes, the fundamental building blocks of chromatin. These nucleosomes are composed of DNA wrapped around a histone octamer, which consists of two copies each of histones H2A, H2B, H3, and H4. The N-terminal tails of histone proteins, including histone H3, protrude from the nucleosome and are subject to various modifications, including citrullination.

Arginine deiminases, also known as peptidylarginine deiminases (PADs), are a family of enzymes responsible for catalyzing the citrullination of arginine residues. These enzymes are calcium-dependent and require the presence of a specific arginine residue within a protein substrate, along with flanking residues that contribute to the substrate binding site.

The citrullination of histone H3R2 by PAD enzymes results in the conversion of a positively charged arginine residue to a neutral citrulline residue. This modification alters the electrostatic interactions between histone H3 and DNA, leading to changes in chromatin structure and accessibility.

Specifically, citrullination at H3R2 has been shown to:

* **Increase chromatin accessibility:** Citrullination at H3R2 reduces the positive charge of the histone tail, weakening its interaction with DNA. This increased accessibility allows for the recruitment of transcription factors and other regulatory proteins, promoting gene expression.
* **Alter chromatin compaction:** Citrullination at H3R2 can affect nucleosome stability and chromatin compaction. This, in turn, can influence the accessibility of DNA to regulatory proteins and ultimately affect gene expression.
* **Regulate DNA replication and repair:** Citrullination at H3R2 has been implicated in the regulation of DNA replication and repair processes. This is likely due to its effects on chromatin structure and accessibility.

In addition to its roles in gene expression, DNA replication, and repair, citrullination at H3R2 has also been linked to various cellular processes, including:

* **Immune responses:** Citrullination at H3R2 is involved in immune responses, particularly in the context of autoimmune diseases. This modification can trigger the production of antibodies that target citrullinated proteins, leading to inflammation and tissue damage.
* **Neurological function:** Citrullination at H3R2 has been implicated in neurological function and diseases. For example, elevated levels of citrullinated histones have been observed in the brains of patients with Alzheimer's disease.

Overall, histone H3R2 arginine deiminase activity represents a crucial post-translational modification that influences chromatin structure, accessibility, and function. This activity plays a critical role in regulating gene expression, DNA replication and repair, and a wide range of cellular processes, including immune responses and neurological function.'
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Proteins (1)

Compounds (19)