Table 2.
PAD isozymes tissue distribution, target substrates, physiological functions and disease association.
| Isozyme | Tissue distribution (Protein level) | Target substrates | Physiological functions | Disease association |
|---|---|---|---|---|
| PAD1 | Skin epidermis, uterus (55) and hair follicles (56) | Keratin and filaggrin (57, 58) | Skin keratinization (59) | Psoriasis (39) |
| PAD2 | Brain, skeletal muscle, spleen, spinal cord, uterus, secretory glands and pancreas (55, 60–62), leukocytes [macrophages (63), neutrophils (64) and T cells (65)] | Myelin basic protein (66), vimentin (63), actin (67), histones (68), fibrinogen and α- enolase (69) | Disassembly of vimentin filaments (70), CNS plasticity (9), epigenetic and transcriptional regulation (71), immune response (65, 72) | Rheumatoid arthritis, multiple sclerosis (73), Alzheimer disease (74) and prion diseases (75) |
| PAD3 | Skin epidermis and hair follicles (55, 56) | Filaggrin, trichohyalin (56, 57), apoptosis-inducing factor (76) | Regulation of epidermal functions (57) | Unknown |
| PAD4 | Leukocytes [mainly granulocytes, such as neutrophils and eosinophils (77, 78), monocytes, macrophages (63) and T cells (65)] and neurons (79) | Histones, nucleophosmin (80), nuclear lamin C (81), antithrombin (82), ING4 (83), NF-Kb (84), fibrinogen and α- enolase (69) | Epigenetic and transcriptional regulation (71), NET formation (85), immune response (65, 85) | Rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (86) and cancers (87) |
| PAD6 | Egg, early embryo and ovary (88) | No substrates identified; no activity in vitro (89) | Oocyte cytoskeletal formation and female fertility (90) | Unknown |
ING4, inhibitor of growth 4; CNS, central nervous system; NET, neutrophil extracellular trap.