Protein-arginine deiminase type-2 (PADI2)

Protein-arginine deiminase type-2 (PAD2), encoded by the PADI2 gene, 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 (UniProt Q9Y2J8). It is the most widely expressed member of the PAD family and plays a critical role in diverse biological processes, including the regulation of gene expression through histone modification (specifically H3R26), myelin stability, and immune cell signaling (PubMed: 24517239, 32075125). In disease states, dysregulated PAD2 activity is a major driver of rheumatoid arthritis (RA) by generating citrullinated autoantigens that trigger the production of anti-citrullinated protein antibodies (ACPA) (PubMed: 37041555). Additionally, PAD2 is implicated in the progression of various cancers, such as breast and prostate cancer, where it acts as an epigenetic co-activator for nuclear receptors like the estrogen receptor (PubMed: 23112218, 32075125). Therapeutic strategies focus on small-molecule inhibitors, such as Cl-amidine and its derivatives, to block its catalytic activity and mitigate inflammatory and oncogenic signaling (PubMed: 28444982).

Other names

Peptidylarginine deiminase IIProtein-arginine deiminase type IIPAD-H19PAD2PADI2

Inhibition of the enzyme's catalytic activity to prevent the conversion of peptidyl-arginine to peptidyl-citrulline, thereby reducing the formation of autoantigens and inhibiting oncogenic gene transcription.