Page last updated: 2024-10-24

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)

ProteinDefinitionTaxonomy
Protein-arginine deiminase type-4A protein-arginine deiminase type-4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UM07]Homo sapiens (human)

Compounds (19)

CompoundDefinitionClassesRoles
azathioprineazathioprine : A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS.

Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)
aryl sulfide;
C-nitro compound;
imidazoles;
thiopurine
antimetabolite;
antineoplastic agent;
carcinogenic agent;
DNA synthesis inhibitor;
hepatotoxic agent;
immunosuppressive agent;
prodrug
leflunomideleflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide.

Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.
(trifluoromethyl)benzenes;
isoxazoles;
monocarboxylic acid amide
antineoplastic agent;
antiparasitic agent;
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
hepatotoxic agent;
immunosuppressive agent;
non-steroidal anti-inflammatory drug;
prodrug;
pyrimidine synthesis inhibitor;
tyrosine kinase inhibitor
mesalaminemesalamine : A monohydroxybenzoic acid that is salicylic acid substituted by an amino group at the 5-position.

Mesalamine: An anti-inflammatory agent, structurally related to the SALICYLATES, which is active in INFLAMMATORY BOWEL DISEASE. It is considered to be the active moiety of SULPHASALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed)
amino acid;
aromatic amine;
monocarboxylic acid;
monohydroxybenzoic acid;
phenols
non-steroidal anti-inflammatory drug
streptonigrinpyridines;
quinolone
antimicrobial agent;
antineoplastic agent
sulfamethoxazolesulfamethoxazole : An isoxazole (1,2-oxazole) compound having a methyl substituent at the 5-position and a 4-aminobenzenesulfonamido group at the 3-position.

Sulfamethoxazole: A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p208)
isoxazoles;
substituted aniline;
sulfonamide;
sulfonamide antibiotic
antibacterial agent;
antiinfective agent;
antimicrobial agent;
drug allergen;
EC 1.1.1.153 [sepiapterin reductase (L-erythro-7,8-dihydrobiopterin forming)] inhibitor;
EC 2.5.1.15 (dihydropteroate synthase) inhibitor;
environmental contaminant;
epitope;
P450 inhibitor;
xenobiotic
sulfapyridinesulfapyridine : A sulfonamide consisting of pyridine with a 4-aminobenzenesulfonamido group at the 2-position.

Sulfapyridine: Antibacterial, potentially toxic, used to treat certain skin diseases.
pyridines;
substituted aniline;
sulfonamide;
sulfonamide antibiotic
antiinfective agent;
dermatologic drug;
drug allergen;
environmental contaminant;
xenobiotic
trimethoprimtrimethoprim : An aminopyrimidine antibiotic whose structure consists of pyrimidine 2,4-diamine and 1,2,3-trimethoxybenzene moieties linked by a methylene bridge.

Trimethoprim: A pyrimidine inhibitor of dihydrofolate reductase, it is an antibacterial related to PYRIMETHAMINE. It is potentiated by SULFONAMIDES and the TRIMETHOPRIM, SULFAMETHOXAZOLE DRUG COMBINATION is the form most often used. It is sometimes used alone as an antimalarial. TRIMETHOPRIM RESISTANCE has been reported.
aminopyrimidine;
methoxybenzenes
antibacterial drug;
diuretic;
drug allergen;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
environmental contaminant;
xenobiotic
streptomycinantibiotic antifungal drug;
antibiotic fungicide;
streptomycins
antibacterial drug;
antifungal agrochemical;
antimicrobial agent;
antimicrobial drug;
bacterial metabolite;
protein synthesis inhibitor
n-benzoyl-l-arginineN-benzoyl-L-arginine : An N-acyl-L-arginine that is L-arginine in which one of the hydrogens attached to the alpha-amino group has been replaced by a benzoyl group.

N-benzoyl-L-arginine: RM given refers to (l)-isomer; structure
benzamides;
N-acyl-L-arginine
benzoylarginine ethyl esterbenzoylarginine ethyl ester: used as substrate for trypsin; RN given refers to parent cpd
methotrexatedicarboxylic acid;
monocarboxylic acid amide;
pteridines
abortifacient;
antimetabolite;
antineoplastic agent;
antirheumatic drug;
dermatologic drug;
DNA synthesis inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
immunosuppressive agent
benzoyl l-arginine methyl esterbenzoyl L-arginine methyl ester: RN given refers to (L-Arg)-isomer
n(alpha)-benzoylarginineamideN(alpha)-benzoylarginineamide: RN given refers to parent cpd(S)-isomer
clindamycinclindamycin : A carbohydrate-containing antibiotic that is the semisynthetic derivative of lincomycin, a natural antibiotic.

Clindamycin: An antibacterial agent that is a semisynthetic analog of LINCOMYCIN.
zithromaxazithromycin : A macrolide antibiotic useful for the treatment of bacterial infections.

Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.
macrolide antibioticantibacterial drug;
environmental contaminant;
xenobiotic
n-alpha-benzoyl-n5-(2-chloro-1-iminoethyl)-l-ornithine amidebenzenes
tetracyclinetetracycline : A broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria.

Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.
chlortetracyclinechlortetracycline : A member of the class of tetracyclines with formula C22H23ClN2O8 isolated from Streptomyces aureofaciens.

Chlortetracycline: A TETRACYCLINE with a 7-chloro substitution.
minocyclineminocycline : A tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5.

Minocycline: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.