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Plasmin
Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin thrombus, clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encoded by the ''PLG'' gene. Function Plasmin is a serine protease that acts to dissolve fibrin blood clots. Apart from fibrinolysis, plasmin proteolysis, proteolyses proteins in various other systems: It activates collagenases, some mediators of the complement system, and weakens the wall of the Graafian follicle, leading to ovulation. Plasmin is also integrally involved in inflammation. It cleaves fibrin, fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin, like trypsin, belongs to the family of serine proteases. Plasmin is released as a zymogen called plasminogen (PLG) from the liver into the systemic circulation. Two major glycoforms of plasminogen are present in humans - type I plasminogen contains two g ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alpha 2-antiplasmin
Alpha 2-antiplasmin (or α2-antiplasmin or plasmin inhibitor) is a serine protease inhibitor (serpin) responsible for inactivating plasmin. Plasmin is an important enzyme that participates in fibrinolysis and degradation of various other proteins. This protein is encoded by the ''SERPINF2'' gene. Structure Alpha 2-antiplasmin (α2AP) is a member of the serine protease inhibitor (serpin) superfamily and is structurally characterized by a central serpin domain flanked by unique N-terminal, N- and C-terminal extensions. The mature human α2AP protein consists of 452 amino acids, with a 12-residue N-terminus, a central serpin domain, and a C-terminal tail of approximately 55 residues. The reactive center loop, which is crucial for its inhibitory function, protrudes from the central serpin domain and contains the Arg364-Met365 peptide bond that is specifically targeted and cleaved by plasmin. There are two main circulating form ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tissue Plasminogen Activator
Tissue-type plasminogen activator, short name tPA, is a protein that facilitates the breakdown of blood clots. It acts as an enzyme to convert plasminogen into its active form plasmin, the major enzyme responsible for clot breakdown. It is a serine protease () found on endothelial cells lining the blood vessels. Human tPA is encoded by the ''PLAT'' gene, and has a molecular weight of ~70 kDa in the single-chain form. tPA can be manufactured using recombinant biotechnology techniques, producing types of recombinant tissue plasminogen activator (rtPA) such as alteplase, reteplase, and tenecteplase. These drugs are used in clinical medicine to treat embolic or thrombotic stroke, but they are contraindicated and dangerous in cases of hemorrhagic stroke and head trauma. The antidote for tPA in case of toxicity is aminocaproic acid. Medical uses tPA is used in some cases of diseases that feature blood clots, such as pulmonary embolism, myocardial infarction, and stroke, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Urokinase
Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally isolated from human urine, and it is also present in the blood and in the extracellular matrix of many tissues. The primary physiological substrate of this enzyme is plasminogen, which is an inactive form ( zymogen) of the serine protease plasmin. Activation of plasmin triggers a proteolytic cascade that, depending on the physiological environment, participates in thrombolysis or extracellular matrix degradation. This cascade had been involved in vascular diseases and cancer progression. Urokinase is encoded in humans by the ''PLAU'' gene, which stands for "plasminogen activator, urokinase". The same symbol represents the gene in other animal species. Function The ''PLAU'' gene encodes a serine protease () involved in degradation of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other cause. In fibrinolysis, a fibrin clot, the product of coagulation, is broken down. Its main enzyme plasmin cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidney and liver. Physiology Plasmin is produced in an inactive form, plasminogen, in the liver. Although plasminogen cannot cleave fibrin, it still has an affinity for it, and is incorporated into the clot when it is formed. Tissue plasminogen activator (t-PA) and urokinase are the agents that convert plasminogen to the active plasmin, thus allowing fibrinolysis to occur. t-PA is released into the blood slowly by the damaged endothelium of the blood vessels, such that, after several days (when th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Urokinase Receptor
The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAUR gene. It is a multidomain glycoprotein tethered to the cell membrane with a (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase (also known as uPA) on the cell surface. Structure uPAR consists of three tandem LU domains, which are protein domains of the three-finger protein family. The structure of uPAR has been solved by X-ray crystallography in complex with a peptide antagonist and with its native ligand, urokinase. All three three-finger domains are necessary for high affinity binding of the primary ligand, urokinase. In addition, uPAR also interacts with several other proteins, including vitronectin, the uPAR associated protein ( uPARAP) and the integrin family of membrane proteins. It has been possible to express uPAR recombinantly in CHO-cells and S2 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kringle Domain
Kringle domains are autonomous protein domains that fold into large loops stabilized by three disulfide linkages. These are important in protein–protein interactions with blood coagulation factors. Their name refers to the Kringle, a Scandinavian pastry which they somewhat resemble. Kringle domains have been found in plasminogen, hepatocyte growth factors, prothrombin, and apolipoprotein(a). Kringles are found throughout the blood clotting and fibrinolytic proteins. Kringle domains are believed to play a role in binding mediators (e.g., membranes, other proteins or phospholipids), and in the regulation of proteolytic activity. Kringle domains are characterised by a triple loop, 3-disulfide bridge structure, whose conformation is defined by a number of hydrogen bonds and small pieces of anti-parallel beta-sheet. They are found in a varying number of copies in some plasma proteins including prothrombin and urokinase-type plasminogen activator, which are serine proteases b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PAN Domain
PAN domains have significant functional versatility fulfilling diverse biological roles by mediating protein-protein and protein-carbohydrate interactions. These domains contain a hair-pin loop like structure, similar to that found in knottins but with a different pattern of disulfide bonds. It has been shown that the N-terminal domains of members of the plasminogen/hepatocyte growth factor family, the apple domains of the plasma prekallikrein/ coagulation factor XI family, and domains of various nematode proteins belong to the same module superfamily, the PAN module. The PAN domain contains a conserved core of three disulfide bridges. In some members of the family there is an additional fourth disulfide bridge that links the N- and C-termini of the domain. The apple domain, as well as other examples of the PAN domain, consists of seven β-strands that fold into a curved antiparallel sheet cradling an α-helix An alpha helix (or α-helix) is a sequence of amino acids i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thrombus
A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulation step in hemostasis in or out of the circulatory system. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cross-linked fibrin protein. The substance making up a thrombus is sometimes called cruor. A thrombus is a healthy response to injury intended to stop and prevent further bleeding, but can be harmful in thrombosis, when a clot obstructs blood flow through a healthy blood vessel in the circulatory system. In the microcirculation consisting of the very small and smallest blood vessels the capillaries, tiny thrombi known as microclots can obstruct the flow of blood in the capillaries. This can cause a number of problems particularly affecting the pulmonary alveolus, alveoli ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Angiostatin
Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor (i.e., it blocks the growth of new blood vessels). Clinical trials have been undertaken for its use in anticancer therapy. Structure Angiostatin is a 38 kDa fragment of a larger protein, plasmin (itself a fragment of plasminogen) enclosing three to five contiguous kringle modules. Each module contains two small beta sheets and three disulfide bonds. There are four different structural variants to angiostatin differing in the combination of kringle domains: K1-3, K1-4, K1-5, K1-4 with a fragment of K-5. Each kringle domain contributes a different element of inhibition to the cytokine. Recent studies through recombinant angiostatin have shown however that K1-3 is pivotal is the inhibitory nature of angiostatin. K1-3 form the “triangular bowl-like structure” of angiostatin. This structure is stabilized by interactions between inter-kringle p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein (encoded by ''KLKB1 gene'') has no known paralogue, while tissue kallikrein-related peptidases (''KLKs'') encode a family of fifteen closely related serine proteases. These genes are localised to chromosome Chromosome 19 (human), 19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation. Occurrence In 1934, Eugen Werle reported finding a substance in the pancreas of humans and various animals in such large amounts that the pancreas could be taken for its site of origin. He named it kallikrein, by derivation from the Greek word καλλίκρεας (''kallíkreas'') 'pancreas'. Since then, similar enzymes have been found in the biological fluids of humans and other mammals, as we ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor XII
Coagulation factor XII, also known as Hageman factor, is a plasma protein involved in coagulation. It is the zymogen form of factor XIIa (), an enzyme of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by ''F12'' gene. Genetics The gene for factor XII is located on the tip of the long arm of the fifth chromosome (5q33-qter). Structure Human Factor XII is 596 amino acids long and consists of two chains, the heavy chain (353 residues) and light chain (243 residues) held together by a disulfide bond. It is 80,000 daltons in molecular weight. The heavy chain contains two fibronectin-type domains (type I and II), two epidermal growth factor-like domains, a kringle domain, and a proline-rich region, while the light chain contains the protease domain. FXII can be cleaved sequentially at two sites, Arg353 and Arg334, with the second cleavage liberating the light chain and forming β-FXIIa. The structure of the FnI-EGF-like tandem domain ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
