PAD2 (human, recombinant)

Peptidyl arginine deiminase 2 (PAD2) 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 composed of an α/β propeller domain, an IgG1 domain that contains calcium binding sites, and an IgG2 domain. PAD2 changes conformation upon calcium binding to the IgG1 domain, which activates PAD2 and allows its substrates to bind.² It is ubiquitously expressed with high expression in the brain, spleen, muscle, and spinal cord and is localized primarily to the cytoplasm but can translocate to the nucleus in response to calcium signaling.^1,3,4,5 PAD2 citrullinates non-histone proteins, such as glial fibrillary acid protein (GFAP), myelin basic protein (MBP), and retinoic acid receptor-related orphan receptor γ (RORγ), as well as histone H3 at arginine 26 (H3R26), to regulate diverse processes ranging from myelination to immune function.³ PADI2, the gene encoding PAD2, is highly expressed in tumors from patients with breast cancer and associated with poor prognosis. It is also overexpressed in a variety of other cancers, including castration-resistant prostate, ovarian, and lung cancers, among others. PAD2 has been found in the synovial fluid of patients with rheumatoid arthritis (RA), and anti-PAD2 antibodies are associated with less severe RA than patients with autoantibodies to PAD4.⁴ Cayman’s PAD2 (human recombinant) protein can be used for enzyme activity assays.

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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. Slade, D.J., Fang, P., Dreyton, C.J., et al. Protein arginine deiminase 2 binds calcium in an ordered fashion: Implications for inhibitor design. ACS Chem. Biol. 10(4), 1043-1053 (2015).

3. Beato, M., and Sharma, P. Peptidyl arginine deiminase 2 (PADI2)-mediated arginine citrullination modulates transcription in cancer. Int. J. Mol. Sci. 21(4), 1351 (2020).

4. Curran, A.M., Naik, P., Giles, J.T., et al. PAD enzymes in rheumatoid arthritis: Pathogenic effectors and autoimmune targets. Nat. Rev. Rheumatol. 16(6), 301-315 (2020).

5. Zheng, L., Nagar, M., Maurais, A.J., et al. Calcium regulates the nuclear localization of protein arginine deiminase 2. Biochemistry 58(27), 3042-3056 (2019).

Gorzeń, O., Mikołajczyk-Martinez, A., Mamun, A.A., et al. Isoform-selective PAD2/PAD4 substrates with unnatural amino acids enable cellular peptidylarginine deiminase activity profiling and reveal vimentin citrullination effects in macrophages. Biochemistry 64(19), 4105-4120 (2025).

Martin, M., Nilsson, S.C., Eikrem, D., et al. Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis. Front. Immunol. 14, 1203506 (2023).

Martín Monreal, M.T., Hansen, B.E., Iversen, P.F., et al. Citrullination of myelin basic protein induces a Th17-cell response in healthy individuals and enhances the presentation of MBP85-99 in patients with multiple sclerosis. J. Autoimmun. 139, 103092 (2023).

Crestani, E., Harb, H., Charbonnier, L.M., et al. Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma. J. Allergy Clin. Immunol. 145(3), 897-906 (2020).

Yao, H., Cao, G., Liu, Z., et al. Inhibition of netosis with PAD inhibitor attenuates endotoxin shock induced systemic inflammation. Int. J. Mol. Sci. 23(21), 13264 (2022).

Monreal, M.T.M., Rebak, A.S., Massarenti, L., et al. Applicability of small-molecule inhibitors in the study of peptidyl arginine deiminase 2 (PAD2) and PAD4. Front. Immunol. 12, 716250 (2021).

Damiana, T., Damgaard, D., Sidelmann, J.J., et al. Citrullination of fibrinogen by peptidylarginine deiminase 2 impairs fibrin clot structure. Clin. Chim. Acta 501, 6-11 (2020).

Damgaard, D., Bawadekar, M., Senolt, L., et al. Relative efficiencies of peptidylarginine deiminase 2 and 4 in generating target sites for anti-citrullinated protein antibodies in fibrinogen, alpha-enolase and histone H3. PLoS One 13(8), e0203214 (2018).