Peptidyl Arginine Deiminase Type IV (PADI4)

PAD; PADI5; PDI4; PDI5; Peptidyl Arginine Deiminase Type V; Peptidylarginine deiminase IV

SPN	R127
HGNC	18368
MGI	1338898
PubMed	21655091
RGD	3290
UniProt	Q9UM07
Wiki	PADI4

PADI4 is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response.

The deduced 663-amino acid protein, approximately 50% identical to rat PAD types I, II, and III and 73% identical with rat keratinocyte PAD IV, is most conserved in the C terminal two-thirds of the sequence. Functional analysis indicated that the recombinant protein is fully active against arginine-containing substrates. Western blot analysis showed that expression of a 67-kD protein is induced by incubation of HL60 cells with differentiation factors.

Reference

"Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3)."
J. Biol. Chem. 274:27786-27792(1999) [PubMed] [Europe PMC] [Abstract]

"Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6."
Gene 330:19-27(2004) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and biological annotation of human chromosome 1."
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils."
J. Leukoc. Biol. 70:46-51(2001) [PubMed] [Europe PMC] [Abstract]

"Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis."
Nat. Genet. 34:395-402(2003) [PubMed] [Europe PMC] [Abstract]

"Histone deimination antagonizes arginine methylation."
Cell 118:545-553(2004) [PubMed] [Europe PMC] [Abstract]

"Human PAD4 regulates histone arginine methylation levels via demethylimination."
Science 306:279-283(2004) [PubMed] [Europe PMC] [Abstract]

"Comparison of enzymatic properties between hPADI2 and hPADI4."
Biochem. Biophys. Res. Commun. 327:192-200(2005) [PubMed] [Europe PMC] [Abstract]

"Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination."
Proc. Natl. Acad. Sci. U.S.A. 102:3611-3616(2005) [PubMed] [Europe PMC] [Abstract]

"Histone deimination as a response to inflammatory stimuli in neutrophils."
J. Immunol. 180:1895-1902(2008) [PubMed] [Europe PMC] [Abstract]

"Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation."
Arthritis Rheum. 62:1630-1640(2010) [PubMed] [Europe PMC] [Abstract]

"Structural basis for Ca(2+)-induced activation of human PAD4."
Nat. Struct. Mol. Biol. 11:777-783(2004) [PubMed] [Europe PMC] [Abstract]

"Structural basis for histone N-terminal recognition by human peptidylarginine deiminase 4."
Proc. Natl. Acad. Sci. U.S.A. 103:5291-5296(2006) [PubMed] [Europe PMC] [Abstract]

"Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization."
Biochemistry 45:11727-11736(2006) [PubMed] [Europe PMC] [Abstract]

"Structural and biochemical analyses of the human PAD4 variant encoded by a functional haplotype gene."
Acta Crystallogr. D 67:112-118(2011) [PubMed] [Europe PMC] [Abstract]

"The development of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-Carboxyl)benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) as second generation protein arginine deiminase (PAD) inhibitors."
J. Med. Chem. 54:6919-6935(2011) [PubMed] [Europe PMC] [Abstract]

"Synthesis and screening of a haloacetamidine containing library to identify PAD4 selective inhibitors."
ACS Chem. Biol. 7:160-165(2012) [PubMed] [Europe PMC] [Abstract]

"High variability of peptidylarginine deiminase 4 (PADI4) in a healthy white population: characterization of six new variants of PADI4 exons 2-4 by a novel haplotype-specific sequencing-based approach."
J. Mol. Med. 82:762-767(2004) [PubMed] [Europe PMC] [Abstract]