Peptidylarginine deiminase 2 (PAD2) (PAD2)

Peptidylarginine deiminase 2 (PAD2) is a calcium-dependent enzyme that catalyzes the post-translational conversion of arginine residues in proteins to citrulline, a process known as citrullination or deimination [1, 6]. As the most widely expressed member of the PAD family, PAD2 is found in various tissues, including the central nervous system, skeletal muscle, and immune cells [6, 10]. It plays a critical role in biological processes such as the regulation of gene expression through histone modification, the modulation of immune responses like NETosis and pyroptosis, and the maintenance of myelin sheath stability [1, 2, 10]. Dysregulation of PAD2 activity is strongly implicated in the pathogenesis of several diseases, most notably rheumatoid arthritis, where it generates citrullinated neoantigens that trigger autoantibody production [1, 10, 19]. It is also linked to neurodegenerative conditions like multiple sclerosis and amyotrophic lateral sclerosis, as well as various cancers, including breast and colorectal cancer, where it acts as an epigenetic regulator [1, 8, 20]. Therapeutic development focuses on selective small-molecule inhibitors, such as AFM-30a and Cl-amidine, which aim to reduce pathological citrullination while minimizing off-target effects on other PAD isozymes [9, 16, 23].

Other names

PADI2Protein-arginine deiminase type-2Peptidyl arginine deiminase, type IIPAD-H19PDI2Peptidylarginine deiminase II

Inhibition of protein citrullination (deimination) through covalent or allosteric binding to the enzyme's active site, typically in a calcium-dependent manner.