Description: Homo sapiens plasminogen (PLG), transcript variant 1, mRNA. RefSeq Summary (NM_000301): The plasminogen protein encoded by this gene is a serine protease that circulates in blood plasma as an inactive zymogen and is converted to the active protease, plasmin, by several plasminogen activators such as tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562. Plasmin cleavage also releases the angiostatin protein which inhibits angiogenesis. Plasmin degrades many blood plasma proteins, including fibrin-containing blood clots. As a serine protease, plasmin cleaves many products in addition to fibrin such as fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin is inactivated by proteins such as alpha-2-macroglobulin and alpha-2-antiplasmin in addition to inhibitors of the various plasminogen activators. Plasminogen also interacts with plasminogen receptors which results in the retention of plasmin on cell surfaces and in plasmin-induced cell signaling. The localization of plasminogen on cell surfaces plays a role in the degradation of extracellular matrices, cell migration, inflamation, wound healing, oncogenesis, metastasis, myogenesis, muscle regeneration, neurite outgrowth, and fibrinolysis. This protein may also play a role in acute respiratory distress syndrome (ARDS) which, in part, is caused by enhanced clot formation and the suppression of fibrinolysis. Compared to other mammals, the cluster of plasminogen-like genes to which this gene belongs has been rearranged in catarrhine primates. [provided by RefSeq, May 2020]. Transcript (Including UTRs) Position: hg19 chr6:161,123,225-161,175,085 Size: 51,861 Total Exon Count: 19 Strand: + Coding Region Position: hg19 chr6:161,123,337-161,174,093 Size: 50,757 Coding Exon Count: 19
ID:PLMN_HUMAN DESCRIPTION: RecName: Full=Plasminogen; EC=3.4.21.7; Contains: RecName: Full=Plasmin heavy chain A; Contains: RecName: Full=Activation peptide; Contains: RecName: Full=Angiostatin; Contains: RecName: Full=Plasmin heavy chain A, short form; Contains: RecName: Full=Plasmin light chain B; Flags: Precursor; FUNCTION: Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells. FUNCTION: Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo. CATALYTIC ACTIVITY: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products. ENZYME REGULATION: Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin. Activated with catalytic amounts of streptokinase. Plasmin activity inhibited by SERPINE2. SUBUNIT: Interacts (both mature PLG and the angiostatin peptide) with CSPG4 and AMOT. Interacts (via the Kringle domains) with HRG; the interaction tethers PLG to the cell surface and enhances its activation (By similarity). INTERACTION: Q6V4L1:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984250; Q6V4L4:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984286; Q6V4L5:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984118; Q6V4L9:- (xeno); NbExp=2; IntAct=EBI-999394, EBI-984197; P00779:skc (xeno); NbExp=2; IntAct=EBI-999394, EBI-1035089; SUBCELLULAR LOCATION: Secreted. Note=Locates to the cell surface where it is proteolytically cleaved to produce the active plasmin. Interaction with HRG tethers it to the cell surface. TISSUE SPECIFICITY: Present in plasma and many other extracellular fluids. It is synthesized in the liver. DOMAIN: Kringle domains mediate interaction with CSPG4. PTM: N-linked glycan contains N-acetyllactosamine and sialic acid. O-linked glycans consist of Gal-GalNAc disaccharide modified with up to 2 sialic acid residues (microheterogeneity). PTM: In the presence of the inhibitor, the activation involves only cleavage after Arg-580, yielding two chains held together by two disulfide bonds. In the absence of the inhibitor, the activation involves additionally the removal of the activation peptide. DISEASE: Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:217090]. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. MISCELLANEOUS: Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot. SIMILARITY: Belongs to the peptidase S1 family. Plasminogen subfamily. SIMILARITY: Contains 5 kringle domains. SIMILARITY: Contains 1 PAN domain. SIMILARITY: Contains 1 peptidase S1 domain. WEB RESOURCE: Name=Wikipedia; Note=Plasmin entry; URL="http://en.wikipedia.org/wiki/Plasmin"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/plg/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P00747
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.