PAD4 (human, recombinant) - Biotinylated

Protein arginine deiminase 4 (PAD4) catalyzes the conversion of arginine residues to citrulline within cellular protein substrates, resulting in the loss of a positive charge, which can alter protein structure and/or function.¹ It is expressed in neutrophils, as well as a variety of tissues, including the brain, liver, lung, and kidney.^1,2,3 PAD4 has a key role in NETosis, a lytic form of cell death characterized by the release of neutrophil extracellular traps (NETs).¹ Upon neutrophil activation, PAD4 translocates to the nucleus where it citrullinates histones, initiating chromatin decondensation and the release of NETs.^2,4,5 Neutrophils isolated from Pad4^-/- mice exhibit decreased citrullination of histone H3 under both basal and LPS-stimulated conditions and are defective for NET formation in response to stimulation with LPS, phorbol 12-myristate 13-acetate (PMA; Item No. 10008014), or hydrogen peroxide.⁴ Pad4^-/- mice exhibit larger lesions than wild-type mice in a model of necrotizing fasciitis induced by M1 group A S. pyogenes lacking the extracellular DNase Sda1. Pad4-deficient mice also exhibit reduced infarct size in a model of myocardial ischemia-reperfusion injury and reduced tumor growth in a Lewis lung carcinoma model.^6,2 PADI4 SNPs, including G55S, V82A, and G112A, are associated with rheumatoid arthritis in humans.⁷ Cayman’s PAD4 (human, recombinant) - Biotinylated protein contains the G55S, V82A, and G112A SNPs and can be used for enzyme activity assays.

WARNING This product is not for human or veterinary use.

1. van Beers, J.J.B.C., Zendman, A.J.W., Raijmakers, R., et al. Peptidylarginine deiminase expression and activity in PAD2 knock-out and PAD4-low mice. Biochimie 95(2), 299-308 (2013).

2. Demers, M., Wong, S.L., Martinod, K., et al. Priming of neutrophils toward NETosis promotes tumor growth. Oncoimmunology 5(5), e1134073 (2016).

3. Jones, J.E., Causey, C.P., Knuckley, B., et al. Protein arginine deiminase 4 (PAD4): Current understanding and future therapeutic potential. Curr. Opin. Drug Discov. Devel. 12(5), 616-627 (2009).

4. Li, P., Li, M., Lindberg, M.R., et al. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J. Exp. Med. 207(9), 1853-1862 (2010).

5. Thiam, H.R., Wong, S.L., Qiu, R., et al. NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture. Proc. Natl. Acad. Sci. USA 117(13), 7326-7337 (2020).

6. Savchenko, A.S., Borissoff, J.I., Martinod, K., et al. VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice. Blood 123(1), 141-148 (2014).

7. Suzuki, A., Yamada, R., Chang, X., et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat. Genet. 34(4), 395-402 (2003).