Scientific background: |
PADI4 (Peptidylarginine Deiminase, Type IV), also known as PAD or PAD4, is a human protein which in humans is encoded by the PADI4 gene. Peptidylarginine deiminases, such as PADI4, make up a family of posttranslational modification enzymes that convert arginine residues to citrulline residues in the presence of calcium ion (Nakashima et al., 1999). Suzuki et al. (2003) found from sequence data that the PADI4 gene maps to 1p36. Cuthbert et al. (2004) described a process, deimination, that converts histone arginine to citrulline and antagonizes arginine methylation. They showed that PADI4 specifically deiminated arg2, arg8, arg17, and arg26 in the H3 tail. Deimination by PADI4 prevented arginine methylation by CARM1. Dimethylation of arginines prevented deimination by PADI4, although monomethylation still allowed deimination to take place. In vivo targeting experiments on an endogenous promoter demonstrated that PADI4 could repress hormone receptor-mediated gene induction. PADI4 was recruited to the pS2 promoter following hormone induction when the gene was transcriptionally downregulated, consistent with a repressive role for PADI4. |
References: |
1. Cuthbert, G. L., Daujat, S., Snowden, A. W., Erdjument-Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P. D., Tempst, P., Bannister, A. J., Kouzarides, T. Histone deimination antagonizes arginine methylation. Cell 118: 545-553, 2004.
2. Nakashima, K., Hagiwara, T., Ishigami, A., Nagata, S., Asaga, H., Kuramoto, M., Senshu, T., Yamada, M. Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1-alpha,25-dihydroxyvitamin D(3). J. Biol. Chem. 274: 27786-27792, 1999.
3. Suzuki, A., Yamada, R., Chang, X., Tokuhiro, S., Sawada, T., Suzuki, M., Nagasaki, M., Nakayama-Hamada, M., Kawaida, R., Ono, M., Ohtsuki, M., Furukawa, H., and 13 others. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nature Genet. 34: 395-402, 2003
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