Gene Symbol: Padi4
Description: peptidyl arginine deiminase, type IV
Alias: Pad4, Pdi4, protein-arginine deiminase type-4, PAD type IV, peptidylarginine deiminase IV, protein-arginine deiminase type IV
Species: mouse
Products:     Padi4

Top Publications

  1. Cuthbert G, Daujat S, Snowden A, Erdjument Bromage H, Hagiwara T, Yamada M, et al. Histone deimination antagonizes arginine methylation. Cell. 2004;118:545-53 pubmed
    ..We show that peptidyl arginine deiminase 4 (PADI4) specifically deiminates, arginine residues R2, R8, R17, and R26 in the H3 tail...
  2. Wood D, Ackerley C, Brand B, Zhang L, Raijmakers R, Mastronardi F, et al. Myelin localization of peptidylarginine deiminases 2 and 4: comparison of PAD2 and PAD4 activities. Lab Invest. 2008;88:354-64 pubmed publisher
    ..Two of these, PAD2 and PAD4, were localized to the myelin sheath by immunogold electron microscopy...
  3. Li P, Li M, Lindberg M, Kennett M, Xiong N, Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207:1853-62 pubmed publisher
    ..We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation...
  4. Rus d A, Ikejiri Y, Ono H, Yonekawa T, Shiraiwa M, Kawada A, et al. Molecular cloning of cDNAs of mouse peptidylarginine deiminase type I, type III and type IV, and the expression pattern of type I in mouse. Eur J Biochem. 1999;259:660-9 pubmed
    ..contains 664 amino acids (75,098 Da) deduced from the coding region of 1995 bases, and the primary structure of PAD type IV consists of 666 amino acids (74,475 Da) deduced from the coding region of 2001 bases...
  5. Hemmers S, Teijaro J, Arandjelovic S, Mowen K. PAD4-mediated neutrophil extracellular trap formation is not required for immunity against influenza infection. PLoS ONE. 2011;6:e22043 pubmed publisher
    ..The role of NETs during virus-mediated lung inflammation is unknown. Peptidylarginine deiminase 4 (PAD4)-mediated deimination of histone H3 and H4 is required for NET formation...
  6. Tanikawa C, Espinosa M, Suzuki A, Masuda K, Yamamoto K, Tsuchiya E, et al. Regulation of histone modification and chromatin structure by the p53-PADI4 pathway. Nat Commun. 2012;3:676 pubmed publisher
    ..vitro citrullination of the arginine 3 residue of histone H4 (cit-H4R3) in response to DNA damage through the p53-PADI4 pathway. We also show DNA damage-induced citrullination of Lamin C...
  7. Kolaczkowska E, Jenne C, Surewaard B, Thanabalasuriar A, Lee W, Sanz M, et al. Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature. Nat Commun. 2015;6:6673 pubmed publisher
    ..By contrast, inhibition of NET production as modelled by PAD4-deficiency, or prevention of NET formation and proteolytic activity as modelled in NE(-/-) mice prevent collateral ..
  8. Wong S, Demers M, Martinod K, Gallant M, Wang Y, Goldfine A, et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med. 2015;21:815-9 pubmed publisher
    ..Expression of peptidylarginine deiminase 4 (PAD4, encoded by Padi4 in mice), an enzyme important in chromatin decondensation, was elevated in neutrophils from individuals with ..
  9. Ham A, Rabadi M, Kim M, Brown K, Ma Z, D AGATI V, et al. Peptidyl arginine deiminase-4 activation exacerbates kidney ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2014;307:F1052-62 pubmed publisher
    ..Here, we tested the hypothesis that PAD4 contributes to ischemic acute kidney injury (AKI) by exacerbating the inflammatory response after renal ischemia-..

More Information


  1. Hägglöf T, Sedimbi S, Yates J, Parsa R, Salas B, Harris R, et al. Neutrophils license iNKT cells to regulate self-reactive mouse B cell responses. Nat Immunol. 2016;17:1407-1414 pubmed publisher
    ..Neutrophils can thus license iNKT cells to regulate potentially harmful autoreactive B cell responses during inflammasome-driven inflammation. ..
  2. Savchenko A, Borissoff J, Martinod K, De Meyer S, Gallant M, Erpenbeck L, et al. VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice. Blood. 2014;123:141-8 pubmed publisher
    ..Finally, we examined the impact of histone citrullination and NETosis by peptidylarginine deiminase 4 (PAD4) on MI/R. We used a 24-hour MI/R mouse surgical model...
  3. Martinod K, Witsch T, Erpenbeck L, Savchenko A, Hayashi H, Cherpokova D, et al. Peptidylarginine deiminase 4 promotes age-related organ fibrosis. J Exp Med. 2017;214:439-458 pubmed publisher
    ..The release of neutrophil extracellular traps (NETs [NETosis]), orchestrated by peptidylarginine deiminase 4 (PAD4), damages organs in acute inflammatory models...
  4. Erpenbeck L, Chowdhury C, Zsengellér Z, Gallant M, Burke S, Cifuni S, et al. PAD4 Deficiency Decreases Inflammation and Susceptibility to Pregnancy Loss in a Mouse Model. Biol Reprod. 2016;95:132 pubmed publisher
    ..factor-mediated pregnancy loss in wild-type (WT) mice and in mice deficient in peptidylarginine deiminase 4 (Padi4-/-) that are unable to form NETs...
  5. Bawadekar M, Shim D, Johnson C, Warner T, Rebernick R, Damgaard D, et al. Peptidylarginine deiminase 2 is required for tumor necrosis factor alpha-induced citrullination and arthritis, but not neutrophil extracellular trap formation. J Autoimmun. 2017;80:39-47 pubmed publisher
    ..However, it is not known which peptidylarginine deiminase (PAD) catalyzes the citrullination seen in inflammation. PAD4 exacerbates inflammatory arthritis and is critical for neutrophil extracellular traps (NETs)...
  6. Leppkes M, Maueröder C, Hirth S, Nowecki S, Günther C, Billmeier U, et al. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis. Nat Commun. 2016;7:10973 pubmed publisher
    ..Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs)...
  7. Subramaniam S, Jurk K, Hobohm L, Jäckel S, Saffarzadeh M, Schwierczek K, et al. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood. 2017;129:2291-2302 pubmed publisher
  8. Biron B, Chung C, Chen Y, Wilson Z, Fallon E, Reichner J, et al. PAD4 Deficiency Leads to Decreased Organ Dysfunction and Improved Survival in a Dual Insult Model of Hemorrhagic Shock and Sepsis. J Immunol. 2018;200:1817-1828 pubmed publisher
    ..activated neutrophils into the extracellular space; they are regulated by the enzyme peptidylarginine deiminase 4 (PAD4) through mediation of chromatin decondensation via citrullination of target histones...
  9. Chavanas S, Méchin M, Takahara H, Kawada A, Nachat R, Serre G, et al. Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene. 2004;330:19-27 pubmed
    ..This study is the first description of the human PADI6 gene and encoded protein, and the first step towards a better understanding of the coordinated regulation of PADI gene expression. ..
  10. Nakashima K, Arai S, Suzuki A, Nariai Y, Urano T, Nakayama M, et al. PAD4 regulates proliferation of multipotent haematopoietic cells by controlling c-myc expression. Nat Commun. 2013;4:1836 pubmed publisher
    Peptidylarginine deiminase 4 (PAD4) functions as a transcriptional coregulator by catalyzing the conversion of histone H3 arginine residues to citrulline residues...
  11. Moscarello M, Lei H, Mastronardi F, Winer S, Tsui H, Li Z, et al. Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis. Dis Model Mech. 2013;6:467-78 pubmed publisher
    ..2CA essentially prevented disease when administered before disease onset or before autoimmune induction, making hypercitrullination, and specifically PAD enzymes, a therapeutic target in MS models and thus possibly in MS. ..
  12. Christophorou M, Castelo Branco G, Halley Stott R, Oliveira C, Loos R, Radzisheuskaya A, et al. Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature. 2014;507:104-8 pubmed publisher
    ..b>PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in ..
  13. Rohrbach A, Hemmers S, Arandjelovic S, Corr M, Mowen K. PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis. Arthritis Res Ther. 2012;14:R104 pubmed publisher
    Both murine and human genome-wide association studies have implicated peptidyl arginine deiminase (PAD4) as a susceptibility gene in rheumatoid arthritis (RA)...
  14. McDonald B, Davis R, Kim S, Tse M, Esmon C, Kolaczkowska E, et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood. 2017;129:1357-1367 pubmed publisher
    ..Together, these data demonstrate, for the first time in an in vivo model of infection, a dynamic NET-platelet-thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis. ..
  15. Rosilio C, Nebout M, Imbert V, Griessinger E, Neffati Z, Benadiba J, et al. L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia. Leukemia. 2015;29:1253-66 pubmed publisher
  16. Seri Y, Shoda H, Suzuki A, Matsumoto I, Sumida T, Fujio K, et al. Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-6-phosphate isomerase-induced arthritis model. Sci Rep. 2015;5:13041 pubmed publisher
    ..Genetic polymorphisms in the PADI4 gene encoding PAD4 are associated with RA susceptibility...
  17. Knight J, Luo W, O Dell A, Yalavarthi S, Zhao W, Subramanian V, et al. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ Res. 2014;114:947-56 pubmed publisher
    ..These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses. ..
  18. Martinod K, Demers M, Fuchs T, Wong S, Brill A, Gallant M, et al. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci U S A. 2013;110:8674-9 pubmed publisher
    ..we adopted a stenosis model of deep vein thrombosis and analyzed venous thrombi in peptidylarginine deiminase 4 (PAD4)-deficient mice that cannot citrullinate histones, a process required for chromatin decondensation and NET ..
  19. Arandjelovic S, McKenney K, Leming S, Mowen K. ATP induces protein arginine deiminase 2-dependent citrullination in mast cells through the P2X7 purinergic receptor. J Immunol. 2012;189:4112-22 pubmed publisher
    ..Our results suggest that P2X7 activation of mast cells may play a role in inflammation by providing PAD2 and PAD2 substrates access to the extracellular space...