Urokinase
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| Urokinase
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| Systematic (IUPAC) name | |
| Human urokinase | |
| Identifiers | |
| CAS number | |
| ATC code | B01 |
| PubChem | ? |
| DrugBank | |
| Chemical data | |
| Formula | C1376H2145N383O406S18 |
| Mol. mass | 31126.5 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
| plasminogen activator, urokinase
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| Identifiers | |
| Symbol | PLAU |
| Entrez | 5328 |
| HUGO | 9052 |
| OMIM | 191840 |
| RefSeq | NM_002658 |
| UniProt | P00749 |
| Other data | |
| EC number | 3.4.21.31 |
| Locus | Chr. 10 q24 |
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WikiDoc Resources for Urokinase | |
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Most recent articles on Urokinase | |
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Evidence Based Medicine | |
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Clinical Trials | |
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Ongoing Trials on Urokinase at Clinical Trials.gov Clinical Trials on Urokinase at Google
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Guidelines / Policies / Govt | |
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US National Guidelines Clearinghouse on Urokinase
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Commentary | |
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Definitions | |
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Patient Resources / Community | |
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Patient resources on Urokinase Discussion groups on Urokinase Directions to Hospitals Treating Urokinase Risk calculators and risk factors for Urokinase
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Healthcare Provider Resources | |
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Causes & Risk Factors for Urokinase | |
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Overview
Urokinase (Abbokinase), also called urokinase-type Plasminogen Activator (uPA), is a serine protease (EC 3.4.21.73). Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix. The primary physiological substrate is plasminogen, which is an inactive zymogen form of the serine protease plasmin. Activation of plasmin triggers a proteolysis cascade which, depending on the physiological environment participate in thrombolysis or extracellular matrix degradation. This links urokinase to vascular diseases and cancer.
Molecular characteristics
Urokinase is a 411 residue protein, consisting of three domains: the serine protease domain, the kringle domain and the growth factor domain. Urokinase is synthesized as a zymogen form (prourokinase or single chain urokinase), and is activated by proteolytic cleavage between L158 and I159. The two resulting chains are kept together by a disulfide bond.
Interaction partners
The most important inhibitors of urokinase are the serpins plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2), which inhibits the protease activity irreversibly. In the extracellular matrix urokinase is tethered to the cell membrane by its interaction to the urokinase receptor.
 Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition. |
Urokinase and cancer
Elevated expression levels of urokinase and several other components of the plasminogen activation system are found to be correlated with tumor malignancy. It is believed that the tissue degradation following plasminogen activation, facilitates tissue invasion and thus contributes to metastasis. This makes urokinase an attractive drug target and inhibitors have been sought to be used as anticancer agents. However incompatibilities between the human and murine system hampers clinical evaluation of these agents. Through its interaction with the urokinase receptor, urokinase affects several other aspects of cancer biology such as cells adhesion, migration and cellular mitotic pathways.
Clinical applications
Urokinase is used clinically as a thrombolytic agent in the treatment of severe or massive deep venous thrombosis, pulmonary embolism, myocardial infarction, and occluded intravenous or dialysis cannulas. Recently, Alteplase has replaced urokinase as a thrombolytic drug in acute infarction.
Proteins: coagulation | |
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| Coagulation factors | intrinsic pathway (FXII, FXI, FIX, FVIII) - extrinsic pathway (Tissue factor, FVII) - common pathway (FX, FV, (Pro)thrombin / FII, Fibrin / FI, FXIII) - HMWK - vWF - Kallikrein |
| Inhibitors | Antithrombin - Protein C - Protein S - Protein Z - ZPI - TFPI |
| Fibrinolysis | Plasmin - tPA/urokinase - PAI-1/2 - α2-AP - α2-macroglobulin - TAFI |
Endopeptidases: serine proteases/serine endopeptidases (EC 3.4.21) | |
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| Digestive system | Enteropeptidase - Trypsin - Chymotrypsin - Elastase (Neutrophil, Pancreatic) |
| Complement system | Factor B - Factor D - Factor I - MASP (MASP1, MASP2) - C3-convertase |
| Coagulation | factors: Thrombin - Factor VIIa - Factor IXa - Factor Xa - Factor XIa - Factor XIIa - Kallikrein (PSA) fibrinolysis: Plasmin - Tissue plasminogen activator - Urinary plasminogen activator |
| Immune system | Chymase - Granzyme - Tryptase - Proteinase 3/Myeloblastin |
| Venombin | Ancrod - Batroxobin |
| Other | Acrosin - Pronase - Proprotein convertases (1, 2) - Subtilisin/Furin - Streptokinase - Prolyl endopeptidase |
WikiDoc Research Resources for Urokinase | |
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| Articles on Urokinase | Most recent articles on Urokinase • Most cited articles on Urokinase • Review articles on Urokinase • Articles on Urokinase in N Eng J Med, Lancet, BMJ |
| Media (Slides, Video, Images, MP3) on Urokinase | Powerpoint slides on Urokinase • Images of Urokinase • Photos of Urokinase • Podcasts & MP3s on Urokinase • Videos on Urokinase |
| Evidence Based Medicine Regarding Urokinase | Cochrane Collaboration on Urokinase • Bandolier on Urokinase • TRIP on Urokinase |
| Cost Effectiveness of Urokinase | Cost Effectiveness of Urokinase |
| Clinical Trials Involving Urokinase | Ongoing Trials on Urokinase at Clinical Trials.gov • Trial results on Urokinase • Clinical Trials on Urokinase at Google |
| Guidelines / Policies / Government Resources (FDA/CDC) Regarding Urokinase | US National Guidelines Clearinghouse on Urokinase • NICE Guidance on Urokinase • NHS PRODIGY Guidance • FDA on Urokinase • CDC on Urokinase |
| Textbook Information on Urokinase | Books and Textbook Information on Urokinase |
| Pharmacology Resources on Urokinase | Dosing of Urokinase • Drug interactions with Urokinase • Side effects of Urokinase • Allergic reactions to Urokinase • Overdose information on Urokinase • Carcinogenicity information on Urokinase • Urokinase in pregnancy • Pharmacokinetics of Urokinase • |
| Genetics, Pharmacogenomics, and Proteinomics of Urokinase | Genetics of Urokinase • Pharmacogenomics of Urokinase • Proteomics of Urokinase |
| Newstories on Urokinase | Urokinase in the news • Be alerted to news on Urokinase • News trends on Urokinase |
| Commentary on Urokinase | Blogs on Urokinase |
| Patient Resources on Urokinase | Patient resources on Urokinase • Discussion groups on Urokinase • Patient Handouts on Urokinase • Directions to Hospitals Treating Urokinase • Risk calculators and risk factors for Urokinase |
| Healthcare Provider Resources on Urokinase | Symptoms of Urokinase • Causes & Risk Factors for Urokinase • Diagnostic studies for Urokinase • Treatment of Urokinase |
| Continuing Medical Education (CME) Programs on Urokinase | CME Programs on Urokinase |
| International Resources on Urokinase | Urokinase en Espanol • Urokinase en Francais |
| Business Resources on Urokinase | Urokinase in the Marketplace • Patents on Urokinase |
| Informatics Resources on Urokinase | List of terms related to Urokinase |
it:Attivatore dell'u-plasminogeno
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
