Urokinase
Explore a selection of our essential drug information below, or:
Overview
- Description
- An anticoagulant or "blood thinner" used to treat blood clots in various illnesses including heart attacks.
- Description
- An anticoagulant or "blood thinner" used to treat blood clots in various illnesses including heart attacks.
- DrugBank ID
- DB00013
- Type
- Biotech
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 1
- Phase 2
- 8
- Phase 3
- 12
- Phase 4
- 6
- Mechanism of Action
- PlasminogenActivator
- Urokinase plasminogen activator surface receptorInducerModulator
- Plasminogen activator inhibitor 1SubstrateInducer
- + 1 more target
- Plasminogen
Identification
- Summary
Urokinase is a low molecular weight form of human urokinase used to treat pulmonary embolism and myocardial infarction as well as to clear IV lines.
- Brand Names
- Kinlytic
- Generic Name
- Urokinase
- DrugBank Accession Number
- DB00013
- Background
Urokinase is an endogenous peptide that is cleaved in the presence of plasmin between lysine 158 and isoleucine 159 to yield active urokinase.2 Urokinase remains connected between these 2 chains by a sulfhydryl bond.2
Urokinase was granted FDA approval on 16 January 1978.3
- Type
- Biotech
- Groups
- Approved, Investigational, Withdrawn
- Biologic Classification
- Protein Based Therapies
Blood factors - Protein Structure
- Protein Chemical Formula
- C1376H2145N383O406S18
- Protein Average Weight
- 31126.5 Da
- Sequences
>DB00013 sequence KPSSPPEELKFQCGQKTLRPRFKIIGGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLMS PCWVISATHCFIDYPKKEDYIVYLGRSRLNSNTQGEMKFEVENLILHKDYSADTLAHHND IALLKIRSKEGRCAQPSRTIQTICLPSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMT VVKLISHRECQQPHYYGSEVTTKMLCAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVS WGRGCALKDKPGVYTRVSHFLPWIRSHTKEENGLAL
Download FASTA Format- Synonyms
- Kinase (enzyme-activating), uro-urokinase
- TCUK
- Tissue culture urokinase
- Two-chain urokinase
- Urochinasi
- Urokinase
- Urokinasum
- Uroquinasa
- External IDs
- WIN 22005
Pharmacology
- Indication
In Canada, urokinase is indicated for lysis of acute massive pulmonary emboli, acute thrombi obstructing coronary arteries, occlusive thromboemboli in peripheral arteries and grafts, and restoration of patency to intravenous catheters.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Acute massive pulmonary embolism •••••••••••• ••••• ••••••••• Treatment of Obstruction; catheter, infusion catheter (vascular) •••••••••••• ••••• ••••••••• Treatment of Pulmonary embolism •••••••••••• ••••• ••••••••••••••• •••••••• ••••••••• Treatment of Thromboembolism of the coronary artery •••••••••••• ••••• ••••••••• Treatment of Thromboembolism of the graft •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Urokinase is a serine protease that activates plasminogen to an active fibrinolytic protease.1 The duration of action is short due to the short half life.3 Patients should be counselled regarding the risk of bleeding, anaphylaxis, infusion reactions, and cholesterol embolization.[L12138
- Mechanism of action
Urokinase is a serine protease.1 It cleaves plasminogen to form the active fibrinolytic protease, plasmin.1
Target Actions Organism APlasminogen activatorHumans AUrokinase plasminogen activator surface receptor inducermodulatorHumans APlasminogen activator inhibitor 1 substrateinducerHumans APlasminogen activator inhibitor 2 substrateinducerHumans UPlasma serine protease inhibitor substrateHumans ULow-density lipoprotein receptor-related protein 2 substrateHumans USuppressor of tumorigenicity 14 protein substrateHumans UNidogen-1 ligandHumans - Absorption
Urokinase is delivered intravenously, so the bioavailability is high.
- Volume of distribution
The volume of distribution of urokinase is 11.5L.3
- Protein binding
Data regarding the protein binding of urokinase in plasma is not readily available.
- Metabolism
Because urokinase is a protein, it is expected to be metabolized by proteases to smaller proteins and amino acids.
- Route of elimination
Urokinase is eliminated in the bile and urine.3
- Half-life
Urokinase has a half life of 12.6±6.2 minutes.3
- Clearance
Data regarding the clearance of urokinase is not readily available.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Patients experiencing an overdose may present with bleeding.4 Treat patients with symptomatic and supportive measures which may include application of local pressure, administration of whole blood or plasma, and administration of aminocaproic acid.4
- Pathways
Pathway Category Urokinase Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab Urokinase may increase the anticoagulant activities of Abciximab. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Urokinase. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Urokinase is combined with Acemetacin. Acenocoumarol Urokinase may increase the anticoagulant activities of Acenocoumarol. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Urokinase. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Abbokinase (Abbott Laboratories)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kinlytic Injection, powder, lyophilized, for solution 250000 [iU]/5mL Intravenous ImaRx Therapeutics, Inc. 2007-06-08 Not applicable US Kinlytic (urokinase for Injection) Powder, for solution 250000 unit / vial Intravenous Microbix Biosystems Inc 1988-12-31 2009-10-28 Canada Kinlytic Open-cath Powder, for solution 5000 unit / vial Intravenous Microbix Biosystems Inc 1991-12-31 2009-10-28 Canada
Categories
- ATC Codes
- B01AD04 — Urokinase
- Drug Categories
- Agents causing angioedema
- Amino Acids, Peptides, and Proteins
- Anticoagulants
- Biological Factors
- Blood and Blood Forming Organs
- Blood Proteins
- Endopeptidases
- Enzymes
- Enzymes and Coenzymes
- Fibrinolytic Agents
- Hydrolases
- Increased Thrombolysis
- Peptide Hydrolases
- Plasminogen Activators
- Proteins
- Serine Endopeptidases
- Serine Proteases
- Urokinase-Type Plasminogen Activator, antagonists & inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 83G67E21XI
- CAS number
- 9039-53-6
References
- Synthesis Reference
Koji Sasaki, Yasukazu Harada, "Urokinase preparation for oral administration." U.S. Patent US4258030, issued November, 1975.
US4258030- General References
- Urano T, Castellino FJ, Suzuki Y: Regulation of plasminogen activation on cell surfaces and fibrin. J Thromb Haemost. 2018 May 20. doi: 10.1111/jth.14157. [Article]
- Kasai S, Arimura H, Nishida M, Suyama T: Primary structure of single-chain pro-urokinase. J Biol Chem. 1985 Oct 5;260(22):12382-9. [Article]
- FDA Approved Drug Products: Kinlytic Urokinase Injection (Discontinued) [Link]
- Health Canada Approved Drug Products: Urokinase Injection [Link]
- External Links
- UniProt
- P00749
- Genbank
- X02419
- PubChem Substance
- 46506299
- 11055
- ChEMBL
- CHEMBL1201420
- Therapeutic Targets Database
- DAP001194
- PharmGKB
- PA451836
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Urokinase
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Aneurysmal Subarachnoid Hemorrhage (A-sah) / Cerebral Vasospasm / Hydrocephaly 1 somestatus stop reason just information to hide Not Available Completed Not Available Ischemic Stroke 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Acute Ischemic Stroke 1 somestatus stop reason just information to hide Not Available Unknown Status Treatment Venous Thrombosis (Disorder) 1 somestatus stop reason just information to hide Not Available Withdrawn Not Available Ischemic Stroke 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Microbix biosystems inc
- Packagers
- Hospira Inc.
- ImaRx Therapeutics
- Microbix Biosystems Inc.
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 250000 [iU]/5mL Powder, for solution Intravenous 250000 unit / vial Powder, for solution Intravenous 5000 unit / vial Solution Injection, powder, lyophilized, for solution Parenteral 500000 IU Injection, powder, for solution Intravenous 100000 IU Injection, powder, for solution Intravenous 1000000 IU Injection, powder, for solution Intravenous 25000 IU Injection, powder, for solution Intravenous 250000 IU Injection, powder, for solution Intravenous 500000 IU Injection, powder, for solution Intravenous bolus; Intravenous drip; Intravitreal 100000 IU/2ML Injection, powder, for solution Intravenous bolus; Intravenous drip; Intravitreal 1000000 IU/5ML Injection, powder, for solution Intravenous bolus; Intravenous drip; Intravitreal 25000 IU/2ML Injection, powder, for solution Intravenous bolus; Intravenous drip; Intravitreal 500000 IU/5ML Injection, powder, for solution Parenteral 1000.000 U.I./5ML Injection, powder, for solution Parenteral 250000 U.I./5ML Injection, powder, for solution Parenteral 500000 U.I./5ML Injection, powder, for solution Injection, powder, lyophilized, for solution Intra-arterial; Intravenous 250000 iu Injection, powder, lyophilized, for solution Intra-arterial; Intravenous 500000 iu Injection, powder, for solution Parenteral Injection, powder, for solution Intravenous 60000 iu Injection, powder, for solution Parenteral 1000.000 UI Powder, for solution Intravenous 500000 UI Powder 60000 IU/1vial - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) 76 °C at pH 4.5 Nowak, U.K. et al., Biochemistry 33:2951-2960 (1994) hydrophobicity -0.466 Not Available isoelectric point 8.66 Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Activator
- General 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
- Specific Function
- apolipoprotein binding
- Gene Name
- PLG
- Uniprot ID
- P00747
- Uniprot Name
- Plasminogen
- Molecular Weight
- 90568.415 Da
References
- Zhang X, Zhou H, Shen G, Liu Z, Hu Y, Wei W, Song S: Study on the mechanism of the annexin II-mediated co-assembly of t-PA and plasminogen. J Huazhong Univ Sci Technolog Med Sci. 2002;22(1):21-3, 76. [Article]
- Lopez-Alemany R, Longstaff C, Hawley S, Mirshahi M, Fabregas P, Jardi M, Merton E, Miles LA, Felez J: Inhibition of cell surface mediated plasminogen activation by a monoclonal antibody against alpha-Enolase. Am J Hematol. 2003 Apr;72(4):234-42. [Article]
- Hashimoto M, Oiwa K, Matsuo O, Ueshima S, Okada K, Okada Y, Okamoto S, Giddings JC, Yamamoto J: Suppression of argatroban-induced endogenous thrombolysis by PKSI-527, and antibodies to TPA and UPA, evaluated in a rat arterial thrombolysis model. Thromb Haemost. 2003 May;89(5):820-5. [Article]
- Guda K, Claffey KP, Dong M, Nambiar PR, Rosenberg DW: Defective processing of the transforming growth factor-beta1 in azoxymethane-induced mouse colon tumors. Mol Carcinog. 2003 May;37(1):51-9. [Article]
- Chang H, Shyu KG, Lin S, Wang BW, Liu YC, Lee CC: Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Commun Adhes. 2002 Sep-Dec;9(5-6):239-47. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- FDA Approved Drug Products: Kinlytic Urokinase Injection (Discontinued) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InducerModulator
- General Function
- Acts as a receptor for urokinase plasminogen activator (PubMed:15677461). Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form
- Specific Function
- enzyme binding
- Gene Name
- PLAUR
- Uniprot ID
- Q03405
- Uniprot Name
- Urokinase plasminogen activator surface receptor
- Molecular Weight
- 36977.62 Da
References
- Czekay RP, Aertgeerts K, Curriden SA, Loskutoff DJ: Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. J Cell Biol. 2003 Mar 3;160(5):781-91. [Article]
- Fuchs T, Allgayer H: Transcriptional regulation of the urokinase receptor (u-PAR)--a central molecule of invasion and metastasis. Biol Chem. 2003 May;384(5):755-61. [Article]
- Kanse SM, Chavakis T, Al-Fakhri N, Hersemeyer K, Monard D, Preissner KT: Reciprocal regulation of urokinase receptor (CD87)-mediated cell adhesion by plasminogen activator inhibitor-1 and protease nexin-1. J Cell Sci. 2004 Jan 26;117(Pt 3):477-85. Epub 2003 Dec 16. [Article]
- Beaufort N, Leduc D, Rousselle JC, Magdolen V, Luther T, Namane A, Chignard M, Pidard D: Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G. J Immunol. 2004 Jan 1;172(1):540-9. [Article]
- Guerrero J, Santibanez JF, Gonzalez A, Martinez J: EGF receptor transactivation by urokinase receptor stimulus through a mechanism involving Src and matrix metalloproteinases. Exp Cell Res. 2004 Jan 1;292(1):201-8. [Article]
- Gutova M, Najbauer J, Gevorgyan A, Metz MZ, Weng Y, Shih CC, Aboody KS: Identification of uPAR-positive chemoresistant cells in small cell lung cancer. PLoS One. 2007 Feb 28;2(2):e243. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInducer
- General Function
- Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:17912461, PubMed:8481516, PubMed:9207454). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084)
- Specific Function
- protease binding
- Gene Name
- SERPINE1
- Uniprot ID
- P05121
- Uniprot Name
- Plasminogen activator inhibitor 1
- Molecular Weight
- 45059.695 Da
References
- Gamberi G, Serra M, Ragazzini P, Magagnoli G, Pazzaglia L, Ponticelli F, Ferrari C, Zanasi M, Bertoni F, Picci P, Benassi MS: Identification of markers of possible prognostic value in 57 giant cell tumors of bone. Oncol Rep. 2003 Mar-Apr;10(2):351-6. [Article]
- Shetty S, Bdeir K, Cines DB, Idell S: Induction of plasminogen activator inhibitor-1 by urokinase in lung epithelial cells. J Biol Chem. 2003 May 16;278(20):18124-31. Epub 2003 Mar 17. [Article]
- Hellgren M: Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-30. [Article]
- Chang H, Shyu KG, Lin S, Wang BW, Liu YC, Lee CC: Cell adhesion induces the plasminogen activator inhibitor-1 gene expression through phosphatidylinositol 3-kinase/Akt activation in anchorage dependent cells. Cell Commun Adhes. 2002 Sep-Dec;9(5-6):239-47. [Article]
- Gerstein ES, Shcherbakov AM, Kaz'min AI, Ognerubov NA, Kushlinskii NE: [Urokinase and tissue type plasminogen activators and their type-1 inhibitor (PAI-1) in gastric cancer]. Vopr Onkol. 2003;49(2):165-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- SubstrateInducer
- General Function
- Inhibits urokinase-type plasminogen activator. The monocyte derived PAI-2 is distinct from the endothelial cell-derived PAI-1
- Specific Function
- serine-type endopeptidase inhibitor activity
- Gene Name
- SERPINB2
- Uniprot ID
- P05120
- Uniprot Name
- Plasminogen activator inhibitor 2
- Molecular Weight
- 46595.84 Da
References
- Swartz JM, Bystrom J, Dyer KD, Nitto T, Wynn TA, Rosenberg HF: Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes. J Leukoc Biol. 2004 Oct;76(4):812-9. Epub 2004 Jul 26. [Article]
- Wygrecka M, Markart P, Ruppert C, Kuchenbuch T, Fink L, Bohle RM, Grimminger F, Seeger W, Gunther A: Compartment- and cell-specific expression of coagulation and fibrinolysis factors in the murine lung undergoing inhalational versus intravenous endotoxin application. Thromb Haemost. 2004 Sep;92(3):529-40. [Article]
- Iglesias D, Alegre J, Aleman C, Ruiz E, Soriano T, Armadans LI, Segura RM, Angles A, Monasterio J, de Sevilla TF: Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions. Eur Respir J. 2005 Jan;25(1):104-9. [Article]
- Grebenchtchikov N, Maguire TM, Riisbro R, Geurts-Moespot A, O'Donovan N, Schmitt M, McGreal G, McDermott E, O'Higgins N, Brunner N, Sweep CG, Duffy MJ: Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration. Oncol Rep. 2005 Jul;14(1):235-9. [Article]
- Fernandez-Soria V, Lleonart ME, Diaz-Fuertes M, Villuendas R, Sanchez-Prieto R, Fabra A, Ramon Y Cajal S: Adenovirus E1A orchestrates the urokinase-plasminogen activator system and upregulates PAI-2 expression, supporting a tumor suppressor effect. Int J Oncol. 2006 Jan;28(1):143-8. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and pro-inflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue- and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid
- Specific Function
- acrosin binding
- Gene Name
- SERPINA5
- Uniprot ID
- P05154
- Uniprot Name
- Plasma serine protease inhibitor
- Molecular Weight
- 45674.315 Da
References
- Uhrin P, Schofer C, Zaujec J, Ryban L, Hilpert M, Weipoltshammer K, Jerabek I, Pirtzkall I, Furtmuller M, Dewerchin M, Binder BR, Geiger M: Male fertility and protein C inhibitor/plasminogen activator inhibitor-3 (PCI): localization of PCI in mouse testis and failure of single plasminogen activator knockout to restore spermatogenesis in PCI-deficient mice. Fertil Steril. 2007 Oct;88(4 Suppl):1049-57. Epub 2007 Apr 16. [Article]
- Espana F, Navarro S, Medina P, Zorio E, Estelles A: The role of protein C inhibitor in human reproduction. Semin Thromb Hemost. 2007 Feb;33(1):41-5. [Article]
- Odet F, Guyot R, Leduque P, Le Magueresse-Battistoni B: Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development. Endocrinology. 2004 Mar;145(3):1481-9. Epub 2003 Nov 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Low-density lipoprotein receptor-related protein 2 mediates endocytosis of urokinase.
- General Function
- Multiligand endocytic receptor (By similarity). Acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity). Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B (By similarity). In the kidney, mediates the tubular uptake and clearance of leptin (By similarity). Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium (By similarity). Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight (By similarity). Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells (By similarity). Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP (By similarity). Mediates renal uptake of metallothionein-bound heavy metals (PubMed:15126248). Together with CUBN, mediates renal reabsorption of myoglobin (By similarity). Mediates renal uptake and subsequent lysosomal degradation of APOM (By similarity). Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1 (By similarity). Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity). Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH (By similarity). Also mediates ShhN transcytosis (By similarity). In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon (By similarity). Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH (By similarity). During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure (By similarity). In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed (By similarity). In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid (By similarity). Involved in neurite branching (By similarity). During optic nerve development, required for SHH-mediated migration and proliferation of oligodendrocyte precursor cells (By similarity). Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent (By similarity). Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG (By similarity). Mediates endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis of angiotensis 1-7 (By similarity). Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation (By similarity). Required for embryonic heart development (By similarity). Required for normal hearing, possibly through interaction with estrogen in the inner ear (By similarity)
- Specific Function
- calcium ion binding
- Gene Name
- LRP2
- Uniprot ID
- P98164
- Uniprot Name
- Low-density lipoprotein receptor-related protein 2
- Molecular Weight
- 521952.77 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Kanalas JJ: Effect of the nephritogenic autoantibody of Heymann's nephritis on plasminogen-binding to gp330 and activation by urokinase. Biochim Biophys Acta. 1993 Nov 25;1225(1):101-6. [Article]
- Kanalas JJ: Analysis of plasmin binding and urokinase activation of plasminogen bound to the Heymann nephritis autoantigen, gp330. Arch Biochem Biophys. 1992 Dec;299(2):255-60. [Article]
- Korenberg JR, Argraves KM, Chen XN, Tran H, Strickland DK, Argraves WS: Chromosomal localization of human genes for the LDL receptor family member glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1). Genomics. 1994 Jul 1;22(1):88-93. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Suppressor of tumorigenicity 14 protein activates urokinase.
- General Function
- Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site (PubMed:10373424). Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing (PubMed:18843291). Proteolytically cleaves and therefore activates TMPRSS13 (PubMed:28710277)
- Specific Function
- serine-type endopeptidase activity
- Gene Name
- ST14
- Uniprot ID
- Q9Y5Y6
- Uniprot Name
- Suppressor of tumorigenicity 14 protein
- Molecular Weight
- 94769.01 Da
References
- Suzuki M, Kobayashi H, Kanayama N, Saga Y, Suzuki M, Lin CY, Dickson RB, Terao T: Inhibition of tumor invasion by genomic down-regulation of matriptase through suppression of activation of receptor-bound pro-urokinase. J Biol Chem. 2004 Apr 9;279(15):14899-908. Epub 2004 Jan 27. [Article]
- Kirchhofer D, Peek M, Li W, Stamos J, Eigenbrot C, Kadkhodayan S, Elliott JM, Corpuz RT, Lazarus RA, Moran P: Tissue expression, protease specificity, and Kunitz domain functions of hepatocyte growth factor activator inhibitor-1B (HAI-1B), a new splice variant of HAI-1. J Biol Chem. 2003 Sep 19;278(38):36341-9. Epub 2003 Jun 18. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Ligand
- General Function
- Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin. Also binds to collagen IV and perlecan. It probably has a role in cell-extracellular matrix interactions
- Specific Function
- calcium ion binding
- Gene Name
- NID1
- Uniprot ID
- P14543
- Uniprot Name
- Nidogen-1
- Molecular Weight
- 136375.93 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Stephens RW, Aumailley M, Timpl R, Reisberg T, Tapiovaara H, Myohanen H, Murphy-Ullrich J, Vaheri A: Urokinase binding to laminin-nidogen. Structural requirements and interactions with heparin. Eur J Biochem. 1992 Aug 1;207(3):937-42. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3
- Specific Function
- calcium ion binding
- Gene Name
- MMP12
- Uniprot ID
- P39900
- Uniprot Name
- Macrophage metalloelastase
- Molecular Weight
- 54001.175 Da
References
- Andolfo A, English WR, Resnati M, Murphy G, Blasi F, Sidenius N: Metalloproteases cleave the urokinase-type plasminogen activator receptor in the D1-D2 linker region and expose epitopes not present in the intact soluble receptor. Thromb Haemost. 2002 Aug;88(2):298-306. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2024 03:50