Target type: molecularfunction
Catalysis of the reaction: H2O + L-arginyl-[protein] = L-citrullyl-[protein] + NH4+, resulting in citrullination of the target protein. This reaction is calcium-dependent. [PMID:27393304]
Protein-arginine deiminase (PAD) activity is a crucial molecular function catalyzed by a family of enzymes that modify proteins by converting arginine residues to citrulline. This post-translational modification, known as citrullination, plays a pivotal role in various cellular processes. PAD enzymes utilize calcium as a cofactor and require the presence of a specific amino acid sequence surrounding the target arginine for efficient activity.
The primary function of PAD enzymes is to deiminate arginine residues within proteins. This process involves the removal of an amino group from the guanidinium group of arginine, replacing it with a keto group, resulting in the formation of citrulline. Citrulline, unlike arginine, lacks a positive charge, leading to alterations in the protein's electrostatic properties and structural conformation.
Citrullination mediated by PAD enzymes can have significant consequences for protein function. It can impact protein-protein interactions, alter enzymatic activity, and modify the susceptibility of proteins to degradation. The effects of citrullination are context-dependent and can vary depending on the specific protein and cellular environment.
PAD activity is tightly regulated and dysregulation of PAD enzymes has been implicated in various pathological conditions, including autoimmune diseases, neurodegenerative disorders, and cancer. In autoimmune diseases like rheumatoid arthritis, PAD activity is linked to the production of autoantibodies against citrullinated proteins, contributing to inflammation and joint damage.
In neurodegenerative disorders like Alzheimer's disease, PAD activity has been associated with the aggregation of amyloid-beta peptides, a key pathological feature of the disease. PAD enzymes have also been shown to play roles in cancer development and progression by modifying proteins involved in cell growth, proliferation, and invasion.
In summary, protein-arginine deiminase activity is a multifaceted molecular function with diverse biological roles. It regulates protein function through citrullination, a post-translational modification that can have significant consequences for cellular processes and contribute to various pathological conditions.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Protein-arginine deiminase type-4 | A protein-arginine deiminase type-4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UM07] | Homo sapiens (human) |
| Protein-arginine deiminase type-2 | A protein-arginine deiminase type-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y2J8] | Homo sapiens (human) |
| Protein-arginine deiminase type-4 | A protein-arginine deiminase type-4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UM07] | Homo sapiens (human) |
| Protein-arginine deiminase type-3 | A protein-arginine deiminase type-3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9ULW8] | Homo sapiens (human) |
| Protein-arginine deiminase type-1 | A protein-arginine deiminase type-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9ULC6] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| azathioprine | azathioprine : 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 |
| leflunomide | leflunomide : 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 |
| mesalamine | mesalamine : 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 |
| streptonigrin | pyridines; quinolone | antimicrobial agent; antineoplastic agent | |
| sulfamethoxazole | sulfamethoxazole : 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 |
| sulfapyridine | sulfapyridine : 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 |
| trimethoprim | trimethoprim : 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 |
| streptomycin | antibiotic antifungal drug; antibiotic fungicide; streptomycins | antibacterial drug; antifungal agrochemical; antimicrobial agent; antimicrobial drug; bacterial metabolite; protein synthesis inhibitor | |
| n-benzoyl-l-arginine | N-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 ester | benzoylarginine ethyl ester: used as substrate for trypsin; RN given refers to parent cpd | ||
| methotrexate | dicarboxylic 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 ester | benzoyl L-arginine methyl ester: RN given refers to (L-Arg)-isomer | ||
| n(alpha)-benzoylarginineamide | N(alpha)-benzoylarginineamide: RN given refers to parent cpd(S)-isomer | ||
| clindamycin | clindamycin : 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. | ||
| zithromax | azithromycin : 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 antibiotic | antibacterial drug; environmental contaminant; xenobiotic |
| n-alpha-benzoyl-n5-(2-chloro-1-iminoethyl)-l-ornithine amide | benzenes | ||
| tetracycline | tetracycline : 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. | ||
| chlortetracycline | chlortetracycline : A member of the class of tetracyclines with formula C22H23ClN2O8 isolated from Streptomyces aureofaciens. Chlortetracycline: A TETRACYCLINE with a 7-chloro substitution. | ||
| minocycline | minocycline : 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. |