Peptidyl arginine deiminase (PADI) 4, PADI2 and PADI3 are able to convert peptidyl arginine to peptidyl citrulline. The guanidino group of arginine is hydrolyzed, yielding a ureido group and ammonia. This deimination (citrullination) mechanism is proposed as an alternative pathway for the reversal of arginine methylation (Cuthbert et al. 2004, Wang et al. 2004), whereby the methyl group was removed from a monomethylarginine residue by conversion of the residue to citrulline, releasing methylamine instead of ammonia. PADI4 was reported to specifically deiminate methylated arginine residues 3, 9, 18, and 27 in Histone H3, preventing arginine methylation by CARM1 (Cuthbert et al. 2004). Deimination may stabilize interactions between Histone H2A and H2B (Shimoyama et al. 2010).
Dysregulation of PADI activity is associated with a range of diseases, including rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis, neural degeneration, COPD, and cancer (Lange et al. 2011, McElwee et al. 2012).