PADI4 deiminates Histones

Stable Identifier
Reaction [transition]
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
15345777 Human PAD4 regulates histone arginine methylation levels via demethylimination

Stallcup, MR, Dou, Y, Coonrod, SA, Wang, Y, McDonald, CH, Lee, YH, Cook, RG, Clarke, S, Wysocka, J, Perlin, JR, Allis, CD, Leonelli, L, Sayegh, J, Roeder, RG, Sonbuchner, LS

Science 2004
15339660 Histone deimination antagonizes arginine methylation

Hagiwara, T, Cuthbert, GL, Gregory, PD, Daujat, S, Bannister, AJ, Snowden, AW, Schneider, R, Kouzarides, T, Tempst, P, Yamada, M, Erdjument-Bromage, H

Cell 2004
17303166 Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro

Egberts, WV, Vossenaar, ER, van Veelen, PA, Drijfhout, JW, Soede-Huijbregts, C, Pruijn, GJ, Raijmakers, R, Raats, J, Zendman, AJ, Rutjes, FP

J. Mol. Biol. 2007
Catalyst Activity

protein-arginine deiminase activity of PADI4,(PADI1,PADI2,PADI3, PADI6) [nucleoplasm]

Orthologous Events
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