Peptidylarginine deiminase 2 (PADI2)

Peptidylarginine deiminase 2 (PADI2) is a calcium-dependent protein-arginine deiminase that catalyzes the post-translational deimination (citrullination) of peptidyl-arginine residues to peptidyl-citrulline, changing protein charge, conformation, and function[1][3][5][6][8]. It is one of five mammalian PADI isozymes and is the most widely expressed family member, present in brain, spinal cord, skeletal muscle, secretory glands, and multiple immune cell types[1][3][5][8]. PADI2 acts on diverse substrates including myelin basic protein, vimentin, histones (such as histone H3 R26), the C-terminal domain of RNA polymerase II, fibrinogen, antithrombin, chemokines, cytokines, and transcription factors such as RUNX2[1][2][3][5]. Through citrullination, PADI2 regulates gene transcription, chromatin decondensation, antigen generation, extracellular trap formation, pyroptosis, apoptosis, macrophage differentiation, and osteoblast differentiation and bone formation[2][3][5]. Dysregulated PADI2 expression or activity has been implicated in autoimmune diseases (via generation of citrullinated autoantigens), inflammatory and thrombotic conditions, sepsis, neurodegeneration, and cancer biology, making it an active area of investigation as a therapeutic enzyme target with several experimental PAD inhibitors under preclinical study[3][4][5][7].

Other names

Peptidyl arginine deiminase type-2Protein-arginine deiminase type-2Protein-arginine deiminase 2PAD2Peptidylarginine deiminase type IIPDI2

Covalent or reversible inhibition of the active-site cysteine of PADI2, blocking calcium-dependent deimination of arginine residues to citrulline in target proteins, thereby modulating gene transcription, immune cell death pathways, and inflammatory signaling[4][5].