Angiostatin (PLG) Antibody – Mouse Monoclonal

The protein encoded by this gene is a secreted blood zymogen that is activated by proteolysis and converted to plasmin and angiostatin. Plasmin dissolves fibrin in blood clots and is an important protease in many other cellular processes while angiostatin inhibits angiogenesis. Defects in this gene are likely a cause of thrombophilia and ligneous conjunctivitis. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

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. Ref.26Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo. Ref.26

Catalytic activity: Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa; higher selectivity than trypsin. Converts fibrin into soluble products. Ref.29

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. Ref.26

Subunit structure: 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. Ref.19 Ref.24 Ref.25 Ref.27 Ref.30

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. Ref.24 Ref.26

Tissue specificity: Present in plasma and many other extracellular fluids. It is synthesized in the liver.

Domain: Kringle domains mediate interaction with CSPG4. Ref.25

Post-translational modification: 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).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.

Involvement in disease: Plasminogen deficiency (PLGD) [MIM:217090]: A disorder 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.48 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56

Miscellaneous: Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot.

Sequence similarities: Belongs to the peptidase S1 family. Plasminogen subfamily.Contains 5 kringle domains.Contains 1 PAN domain.Contains 1 peptidase S1 domain.