PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease.
Peptidylarginine deiminase (PAD, EC 3.5.3.15) enzymes catalyze the conversion of protein-bound arginine to citrulline. This post-translational modification may have a big impact on the structure and function of the target protein. In this review, we will discuss the effects of citrullination and its involvement in several human diseases, including rheumatoid arthritis and multiple sclerosis. So far, four isotypes of PAD have been described in mammals. We describe the existence of PAD in non-mammalian vertebrates and the existence of a fifth mammalian PAD. In addition, tissue-specific expression, genomic organization and evolutionary conservation of the different PAD isotypes will be discussed in detail. This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2003/25/v25.1106.html.
Vossenaar
Erik R
ER
Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands. e.vossenaar@ncmls.kun.nl
Zendman
Albert J W
AJ
van Venrooij
Walther J
WJ
Pruijn
Ger J M
GJ
D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology; D006801:Humans; D006867:Hydrolases / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D007527:Isoenzymes / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009103:Multiple Sclerosis / Q000201:enzymology; D010802:Phylogeny; D011487:Protein Conformation; D000076342:Protein-Arginine Deiminases; D011565:Psoriasis / Q000201:enzymology; D016415:Sequence Alignment
D007527:Isoenzymes; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases