Table 9:
Cardiovascular and Metabolic Diseases, and Stroke
| Protease/Inhibitor | Uniprot | Action |
|---|---|---|
| Factor VII (F7) | P08709 | Complexes with Tissue Factor |
| VIIa/TF converts/activates X to XA | ||
| VIIa/TF converts/activates IX to IXa | ||
| Factor IX (or Christmas factor) (F9) | P00740 | Converts/activates factor X |
| Activates factor VII to form factor VIIa | ||
| Activates factor X to form factor Xa | ||
| Factor X (Stuart–Prower factor) (F10) | P00742 | Converts/activates prothrombin to thrombin |
| Complexes with phospholipids & calcium | ||
| Activates factor VII to form factor VIIa | ||
| Thrombin (Prothrombin) | P00734 | Converts fibrinogen to fibrin |
| Activates factors V, VII, VIII, XI, XIII | ||
| Complexes with thrombomodulin | ||
| Thrombin/thrombomodulin activates protein C | ||
| Factor XI (Plasma thromboplastin antecedent) | P03951 | Activates factor IX |
| Inhibited by protein Z-dependent protease inhibitor (ZPI) | ||
| Coagulation factor XII (Hageman factor) | P00748 | Reciprocal activation of Prekallikrein |
| Prekallikrein (Plasma kallikrein) | P03952 | Reciprocal activation of factor XII |
| C1-inhibitor (Plasma protease C1 inhibitor)* | P05155 | Complexes with/Inactivates C1r, C1s, MASP 1, MASP 2, chymotrypsin, kallikrein, fXIa, FXIIa |
| * complement activation, blood coagulation, fibrinolysis and the generation of kinins | ||
| Protein C (Vitamin Kdependent protein C) | P04070 | Inactivates factors Va and VIIIa in the presence of calcium ions and phospholipids |
| Activated by Thrombin/thrombomodulin complex | ||
| Factor V | P12259 | Cofactor required by factor Xa |
| Activated by Thrombin | ||
| Degraded by protein C | ||
| Factor VIII (FVIII) | P00451 | Cofactor required by factor IXa |
| Deficiency results in hemophillia A | ||
| High levels implicated in deep vein thrombosis and pulmonary embolism | ||
| Antithrombin (Antithrombin-III) | P01008 | Inhibits thrombin & factors IXa, Xa and XIa |
| Activity enhanced by heparin | ||
| Heparin cofactor II | P05546 | Inhibits thrombin & factors IXa, Xa and XIa |
| Inhibits chymotrypsin | ||
| Alpha 2-antiplasmin (or α2-antiplasmin or plasmin inhibitor) | P08697 | Inhibits plasmin and trypsin |
| Inactivates matriptase-3/TMPRSS7 and chymotrypsin | ||
| Plasmin | P00747 | Dissolves the fibrin of blood clots |
| tPA (Tissue plasminogen activator) | P00750 | Converts plasminogen to plasmin on the fibrin surface |
| Displaces plasmin from fibrin, promoting inhibition by alpha-2-antiplasmin | ||
| Mast cell chymase | P23946 | Major secreted protease of mast cells |
| Release may promote inflammatory response | ||
| Converts angiotensin I to angiotensin II | ||
| Tryptase {6 isoforms, see previous list table} | Major neutral protease present in mast cells | |
| Resistant to endogenous proteinase inhibitors | ||
| Active only as heparin-stabilized tetramers | ||
| Six Isoforms: Tryptase alpha/beta-1(Q15661) | ||
| Tryptase beta-2(P20231), Tryptase delta(Q9BZJ3) | ||
| Tryptase gamma(Q9NRR2), Brain-specific serine protease 4(Q9GZN4) | ||
| pro-MMP-9 (MMP-9) | P14780 | Cleaves collagen IV and V and fibronectin |
| Implicated in neovascularization in malignant gliomas | ||
| pro-MMP-1 (MMP-1) | P03956 | Cleaves collagens I, II, III, VII, and X |
| Mediates neurotoxicity of HIV viral Tat protein | ||
| pro-MMP-2 (MMP-2) | P08253 | Degrades extracellular matrix proteins, including collagen I and IV |
| pro-MMP-3 (MMP-3) | P08254 | Degrades fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans |
| Activates MMPs 1, 7, and 9 | ||
| Proteinase-3 (PRTN3) | P24158 | Degrades elastin, fibronectin, and collagen (in vitro) |
| Target antigen for anti-neutrophil cytoplasmic antibodies (ANCA) | ||
| Kallikrein 13 | Q9UKR3 | cleaves kininogen to the pro-inflammatory bradykinin |
| Cathepsin A | P10619 | Protects beta-galactosidase and neuraminidase |
| Cathepsin C (CTSC) | P53634 | Activates elastase, cathepsin G, granzymes A and B, neuraminidase, factor XIII, chymase, and tryptase |
| Cathepsin D | P07339 | Intracellular degradation and protein turnover |
| Used by macrophages to degrade bacterial proteins | ||
| Activates ADAM30, implicated in Alzheimer’s progression | ||
| Implicated in metastasis in breast cancer | ||
| Cathepsin L1 | P07711 | Intracellular degradation and protein turnover |
| Degrades collagen ad elastin | ||
| Degrades alpha-1 protease inhibitor | ||
| Cathepsin X/Z/P | Q9UBR2 | Lysosomal protease, cleaves C-terminal residue |
| Calpain-10 | Q9HC96 | Limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction |
| Cathepsin K | P43235 | Cleaves elastin, collagen, and gelatin |
| Involved in breakdown of bone for remodeling | ||
| Implicated in emphysema | ||
| Activated by inflammatory cytokines | ||
| Degraded by cathepsin S | ||
| Caspase-3 (CASP3) | P42574 | Activates caspases 6, 7, and 9 |
| Activated by caspases 8 and 9 | ||
| Cleaves poly(ADP-ribose) polymerase (PARP) | ||
| Cleaves and activates sterol regulatory element binding proteins (SREBPs) | ||
| Implicated in Huntington's disease | ||
| Caspase-6 | P55212 | Dis-inhibits immune system, cleaves interleukin-10 and interleukin-1 receptor-associated kinase 3 |
| Cleaves poly(ADP-ribose) polymerase (PARP) and lamins | ||
| Implicated in Huntington's and Alzheimer's | ||
| Caspase-8 | Q14790 | Activates caspases 3, 4, 6, 7, 9, and 10 |
| Activated by death receptors via FADD | ||
| Factor VII activating protease (FSAP) | Q14520 | Activates factor VII and pro-urokinase |
| May act as tumor suppressor | ||
| Tissue inhibitor of metalloproteinase-1 (TIMP-1) | P01033 | Irreversibly inhibits MMP 1, 2, 3, 7, 8, 9, 10, 11, 12, 13, and 16 |
| Activates integrin signaling via CD63 and ITGB1 |
Cardiovascular and Metabolic Diseases, and Stroke: Activities and uniprot ID codes (where applicable) of proteases, protease inhibitors, and cofactors associated with cardiovascular disease, metabolic diseases, and stroke.