Active • Host: E. coli • AA: 2-663 (full length) • Tag: N-terminal His-GST • MW: 103.2 kDa
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PAD4 (human, recombinant; His- and GST-tagged)

Item No. 25915

Technical Information
Synonyms
  • PADI4
  • PADI5
  • Peptidylarginine Deiminase 4
  • Protein Arginine Deiminase Type 4
  • Protein Arginine Deiminase Type IV
Purity
≥80% estimated by SDS-PAGE
Source
Active recombinant N-terminal His-GST-tagged PAD4 expressed in E. coli
Amino Acids
2-663 (full length)
MW
103.2 kDa
50 mM HEPES, pH 8.0, 300 mM sodium chloride, 1mM DTT, and 10% glycerol
Specific Activity
batch specific
UniProt Accession №
Q9UM07
Shipping & Storage Information
Storage
-80°C
Shipping
Dry ice in continental US; may vary elsewhere
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    NET Formation Screening & Analysis Services
    Our experts are here to help.
    • Detection of NET formation ex vivo and screening for modulators using:
      • High-content imaging
      • Enzymatic detection
      • Citrullination/carbamylation detection
    • Experienced scientists skilled in neutrophil biology, isolation, and handling
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    Product Description

    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 Serum PAD4 autoantibodies have been found in patients with rheumatoid arthritis and are associated with disease severity.7 Cayman’s PAD4 (human, recombinant; His- and GST-tagged) protein can be used for enzyme activity assays. This protein contains two types of affinity tags, His and GST, that allow for flexibility in the removal of PAD4 following citrullination reactions and an enterokinase cleavage site that facilitates removal of both the His and GST tags.

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. van Beers, J.J.B.C., Zendman, A.J.W., Raijmakers, R., et alPeptidylarginine 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 alPriming of neutrophils toward NETosis promotes tumor growth. Oncoimmunology 5(5), e1134073 (2016).

    3. Jones, J.E., Causey, C.P., Knuckley, B., et alProtein 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 alPAD4 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 alNETosis 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 alVWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice. Blood 123(1), 141-148 (2014).

    7. Halvorsen, E.H., Pollmann, S., Gilboe, I.M., et alSerum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity. Ann. Rheum. Dis. 67(3), 414-417 (2008).