title: Peptidylarginine deiminase 4 and citrullination in health and disease.
abstract: Deimination is catalyzed by a family of calcium binding enzymes, called peptidylarginine deiminases (PADs). Among these, the PAD4 isoform has been more extensively studied for its role in some autoimmune diseases. PAD4 is localized in the cytoplasm of monocytes, T and B cells, neutrophils, eosinophils and NK cells and can move to the nucleus upon cell activation. PAD4 plays a physiological role in gene regulation via citrullination of histones. In rheumatoid arthritis (RA), PAD4 contributes to the generation of ACPA specific substrates and is itself a target of autoantibodies; alleles of the PADI4 gene confer susceptibility to RA in Asians but not in Caucasians. In multiple sclerosis, extensive deimination of brain proteins is observed in active lesions, but no role for the PADI4 gene in susceptibility to MS has been so far described.
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, University of Pisa, 56126 Pisa, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Anzilotti
authors.forename: Federico
authors.initials: F
authors.lastname: Pratesi
authors.forename: Cristina
authors.initials: C
authors.lastname: Tommasi
authors.forename: Paola
authors.initials: P
authors.lastname: Migliorini
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D002956:Citrulline / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
chemical_list: D002956:Citrulline; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases