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Protein-arginine deiminase type-4

Definition:

Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Required for the formation of neutrophil extracellular traps (NETs); NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.

References:

[1]. Graeme L Cuthbert, et al. Histone deimination antagonizes arginine methylation. Cell. 2004 Sep 3;118(5):545-53. [Content Brief]

[2]. Indira Neeli, et al. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol. 2008 Feb 1;180(3):1895-902. [Content Brief]

[3]. Yanming Wang, et al. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science. 2004 Oct 8;306(5694):279-83. [Content Brief]

[4]. Kyouhei Arita, et al. Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4. Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5291-6. [Content Brief]

[5]. Young-Ho Lee, et al. Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3611-6. [Content Brief]

[6]. Naoki Horikoshi, et al. Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene. Acta Crystallogr D Biol Crystallogr. 2011 Feb;67(Pt 2):112-8. [Content Brief]

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