Table 1.
Proprotein convertases. The table depicts the main characteristics of the PCs, including the recognition and cleavage sequence, localization, and cognate pathophysiological processes.
| PC | Cleavage sequence | Subcellular localization | Tissue distribution | Proteins activated after PC cleavage | Pathophysiological processes | Ref. |
|---|---|---|---|---|---|---|
| PCSK-1 | (K/R)-(X)-(K/R) | Vesicles in neuroendocrine tissue | Neuroendocrine tissue, brain Pancreas, heart | Proenkephalin, Proopiomelanocortin | Dwarfism Obesity | [102] [103–107] |
| PCSK-2 | (K/R)-(X)-(K/R) | Vesicles | Neuroendocrine tissue, brain | Proopiomelanocortin Prodynorphin | Susceptibility to diabetes | [108] |
|
PCSK-3 Furin |
(K/R)-(X)-(K/R) | TGN/PM | Ubiquitous | Membrane-type metalloproteinases, IGF-1R | Cancer | |
| PCSK-4 | (K/R)-(X)-(K/R) | (acrosomal) PM | Epididymis Spermatocyte | ADAM-1, IGF-2 (?) | Infertility | [109, 110] |
| PCSK-5 | (K/R)-(X)-(K/R) | PCSK-5A: extracellular PCSK-5B: dense secretory granules | Heart, great blood vessels Kidneys, small intestine |
Pro-renin Integrin α subunit MT1-MMP | Cardiovascular disease | [111] |
| PCSK-6 | (K/R)-(X)-(K/R) | Extracellular | Ubiquitous | Similar to furin | Prostate cancer | [16, 17] |
| PCSK-7 | (K/R)-(X)-(K/R) | TGN/PM | Ubiquitous | Pro-EGF | Learning and memory impairments | [112, 113] |
|
PCSK-8 (SKI-1) |
(R/K)X(hydrophobic)Z | TGN/PM | Ubiquitous | Pro-neurotrophic derived factor SREBP-1 and 2 | Viral glycoproteins | [2, 114, 115] |
| PCSK-9 | LVFAQSIP | ER/endosomes | Hepatocytes | PCSK-9 targets LDLR to lysosomal degradation | Atherosclerosis | [32, 116] |