Plasmin
Encyclopedia
Plasmin is an important enzyme
present in blood
that degrades many blood plasma
proteins, most notably, fibrin
clots
. The degradation of fibrin is termed fibrinolysis
. In humans, the plasmin protein is encoded by the PLG gene
.
that acts to dissolve fibrin
blood clots. Apart from fibrinolysis, plasmin 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
). It cleaves fibrin
, fibronectin
, thrombospondin
, laminin, and von Willebrand factor
. Plasmin, like trypsin
, belongs to the family of serine protease
s.
Plasmin is released as a zymogen
called plasminogen (PLG) from the liver into the systemic circulation. Plasminogen is converted into active plasmin by a variety of enzymes, including tissue plasminogen activator
(tPA), urokinase plasminogen activator (uPA), kallikrein
, and factor XII
(Hageman factor). Fibrin is a cofactor for plasminogen activation by tissue plasminogen activator. Urokinase plasminogen activator receptor (uPAR) is a cofactor for plasminogen activation by urokinase plasminogen activator. The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-560 and Val-561.
Plasmin cleavage produces angiostatin
.
, as clots are not degraded adequately. Plasminogen deficiency in mice leads to defective liver repair, defective wound healing, reproductive abnormalities.
In human, a rare disorder called plasminogen deficiency type I (OMIM 217090) is caused by mutations of the PLG gene and is often manifested by ligneous conjunctivitis.
with Thrombospondin 1
, Alpha 2-antiplasmin
and IGFBP3
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
present in blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
that degrades many blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
proteins, most notably, fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
clots
Thrombus
A thrombus , or blood clot, is the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system...
. The degradation of fibrin is termed fibrinolysis
Fibrinolysis
Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. This process has two types: primary fibrinolysis and secondary fibrinolysis...
. In humans, the plasmin protein is encoded by the PLG gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Plasmin is a serine proteaseSerine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
that acts to dissolve fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
blood clots. Apart from fibrinolysis, plasmin proteolyses
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
proteins in various other systems: It activates collagenases, some mediators of the complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
and weakens the wall of the Graafian follicle (leading to ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
). It cleaves fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
, fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
, thrombospondin
Thrombospondin
Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.-Types:The thrombospondins are a family of multifunctional proteins...
, laminin, and von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
. Plasmin, like trypsin
Trypsin
Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...
, belongs to the family of serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
s.
Plasmin is released as a zymogen
Zymogen
A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...
called plasminogen (PLG) from the liver into the systemic circulation. Plasminogen is converted into active plasmin by a variety of enzymes, including tissue plasminogen activator
Tissue plasminogen activator
Tissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown...
(tPA), urokinase plasminogen activator (uPA), kallikrein
Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein has no known homologue, while tissue kallikrein-related peptidases encode a family of fifteen closely related serine proteases...
, and factor XII
Factor XII
Coagulation factor XII also known as Hageman factor is a plasma protein. It is the zymogen form of factor XIIa, an enzyme of the serine protease class. In humans, factor XII is encoded by the F12 gene.- Function :...
(Hageman factor). Fibrin is a cofactor for plasminogen activation by tissue plasminogen activator. Urokinase plasminogen activator receptor (uPAR) is a cofactor for plasminogen activation by urokinase plasminogen activator. The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-560 and Val-561.
Plasmin cleavage produces angiostatin
Angiostatin
Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor , and it is currently undergoing clinical trials for its use in anticancer therapy.-Structure:Angiostatin is a 38 kDa fragment of a larger protein, plasmin ...
.
Pathology
Deficiency in plasmin may lead to thrombosisThrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, as clots are not degraded adequately. Plasminogen deficiency in mice leads to defective liver repair, defective wound healing, reproductive abnormalities.
In human, a rare disorder called plasminogen deficiency type I (OMIM 217090) is caused by mutations of the PLG gene and is often manifested by ligneous conjunctivitis.
Interactions
Plasmin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Thrombospondin 1
Thrombospondin 1
Thrombospondin 1, also known as THBS1, is a protein that in humans in encoded by the THBS1 gene.Thrombospondin 1 is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to...
, Alpha 2-antiplasmin
Alpha 2-antiplasmin
Alpha 2-antiplasmin is a serine protease inhibitor responsible for inactivating plasmin, an important enzyme that participates in fibrinolysis and degradation of various other proteins...
and IGFBP3
IGFBP3
Insulin-like growth factor-binding protein 3, also known as IGFBP3, is a protein that, in humans, is encoded by the IGFBP3 gene.- Function :...
.
Further reading
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: S01.233