Protein-arginine deiminase type-3 (PAD3)

Protein-arginine deiminase type-3 (PAD3) is a calcium-dependent enzyme that catalyzes the post-translational modification of arginine residues into citrulline, a process known as deimination or citrullination [1, 8]. This modification significantly alters the charge and structural properties of proteins such as trichohyalin and filaggrin, which are essential for proper hair follicle formation and epidermal differentiation [3, 7]. PAD3 is primarily expressed in the skin's stratum corneum and hair follicles, and its activity is crucial for maintaining the cylindrical shape of the hair shaft [1, 20]. Mutations in the PADI3 gene are the primary cause of Uncombable Hair Syndrome 1 and have been linked to Central Centrifugal Cicatricial Alopecia [3, 6, 18]. Beyond its role in dermatology, PAD3 is implicated in the pathogenesis of rheumatoid arthritis and various cancers, where it can act as either a tumor suppressor or a driver of drug resistance [4, 13, 17]. Therapeutic targeting of PAD3 involves small-molecule inhibitors like Streptonigrin and haloacetamidine derivatives, which aim to modulate its enzymatic activity in inflammatory and oncological settings [9, 10, 19].

Other names

PADI3Peptidylarginine deiminase IIIPeptidyl arginine deiminase type IIIUHS1

Inhibition of calcium-dependent peptidylarginine deiminase activity, preventing the post-translational conversion of peptidyl-arginine to peptidyl-citrulline and thereby modulating protein-protein interactions and structural stability.