PADI4: Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1. Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA). It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context. Belongs to the protein arginine deiminase family.
Protein type: Nuclear receptor co-regulator; EC 3.5.3.15; Hydrolase
Chromosomal Location of Human Ortholog: 1p36.13
Cellular Component: cytosol; nucleoplasm; nucleus
Molecular Function: arginine deiminase activity; calcium ion binding; protein binding; protein-arginine deiminase activity
Biological Process: chromatin modification; chromatin remodeling; establishment and/or maintenance of chromatin architecture; innate immune response; nucleosome assembly; peptidyl-citrulline biosynthetic process from peptidyl-arginine; protein modification process; regulation of transcription, DNA-dependent; stem cell maintenance; transcription, DNA-dependent
Disease: Rheumatoid Arthritis
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