The human gene is found on the short arm of Chromosome 1 near the telomere (1p36.13). It is located on the Watson (plus) strand and is 55,806 bases long. The protein is 663 amino acids long with a molecular weight of 74,095 Da.[5]
This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine to citrulline residues (citrullination). This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response.[6] PADI4 plays a role in the epigenetics,[7] the deimination of arginines on histones H3 and H4 can act antagonistically to arginine methylation.[8]
The protein may be found in oligomers and binds 5 calcium ions per subunit. It catalyses the reaction:
Protein L-arginine + H2O = protein L-citrulline + NH4+
Asaga H, Nakashima K, Senshu T, Ishigami A, Yamada M (July 2001). "Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils". Journal of Leukocyte Biology. 70 (1): 46–51. doi:10.1189/jlb.70.1.46. PMID11435484. S2CID11448270.
Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, et al. (August 2003). "Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis". Nature Genetics. 34 (4): 395–402. doi:10.1038/ng1206. PMID12833157. S2CID20136298.
Barton A, Bowes J, Eyre S, Spreckley K, Hinks A, John S, Worthington J (April 2004). "A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population". Arthritis and Rheumatism. 50 (4): 1117–1121. doi:10.1002/art.20169. PMID15077293.
Chavanas S, Méchin MC, Takahara H, Kawada A, Nachat R, Serre G, Simon M (April 2004). "Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6". Gene. 330: 19–27. doi:10.1016/j.gene.2003.12.038. PMID15087120.
Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M (August 2004). "Structural basis for Ca(2+)-induced activation of human PAD4". Nature Structural & Molecular Biology. 11 (8): 777–783. doi:10.1038/nsmb799. PMID15247907. S2CID11947135.
Hoppe B, Heymann GA, Tolou F, Kiesewetter H, Doerner T, Salama A (November 2004). "High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach". Journal of Molecular Medicine. 82 (11): 762–767. doi:10.1007/s00109-004-0584-6. PMID15338034. S2CID8356741.
Nakayama-Hamada M, Suzuki A, Kubota K, Takazawa T, Ohsaka M, Kawaida R, et al. (February 2005). "Comparison of enzymatic properties between hPADI2 and hPADI4". Biochemical and Biophysical Research Communications. 327 (1): 192–200. doi:10.1016/j.bbrc.2004.11.152. PMID15629448.
Kearney PL, Bhatia M, Jones NG, Yuan L, Glascock MC, Catchings KL, et al. (August 2005). "Kinetic characterization of protein arginine deiminase 4: a transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis". Biochemistry. 44 (31): 10570–10582. doi:10.1021/bi050292m. PMID16060666.
Ikari K, Kuwahara M, Nakamura T, Momohara S, Hara M, Yamanaka H, et al. (October 2005). "Association between PADI4 and rheumatoid arthritis: a replication study". Arthritis and Rheumatism. 52 (10): 3054–3057. doi:10.1002/art.21309. PMID16200584.
Chang X, Han J (March 2006). "Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors". Molecular Carcinogenesis. 45 (3): 183–196. doi:10.1002/mc.20169. PMID16355400. S2CID40916607.
