Urokinase

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
US Approved
YES
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
1
Phase 2
8
Phase 3
12
Phase 4
6
Therapeutic Categories
  • Fibrinolytic Agents

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Approved, Investigational, Withdrawn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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAcute massive pulmonary embolism••••••••••••••••••••••••••
Treatment ofObstruction; catheter, infusion catheter (vascular)••••••••••••••••••••••••••
Treatment ofPulmonary embolism•••••••••••••••••••••••••••••••• •••••••••••••••••
Treatment ofThromboembolism of the coronary artery••••••••••••••••••••••••••
Treatment ofThromboembolism of the graft••••••••••••••••••••••••••
Contraindications & Blackbox Warnings
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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

TargetActionsOrganism
APlasminogen
activator
Humans
AUrokinase plasminogen activator surface receptor
inducer
modulator
Humans
APlasminogen activator inhibitor 1
substrate
inducer
Humans
APlasminogen activator inhibitor 2
substrate
inducer
Humans
UPlasma serine protease inhibitor
substrate
Humans
ULow-density lipoprotein receptor-related protein 2
substrate
Humans
USuppressor of tumorigenicity 14 protein
substrate
Humans
UNidogen-1
ligand
Humans
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
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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
PathwayCategory
Urokinase Action PathwayDrug 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.
DrugInteraction
AbciximabUrokinase may increase the anticoagulant activities of Abciximab.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Urokinase.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Urokinase is combined with Acemetacin.
AcenocoumarolUrokinase may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidAcetylsalicylic 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

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International/Other Brands
Abbokinase (Abbott Laboratories)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KinlyticInjection, powder, lyophilized, for solution250000 [iU]/5mLIntravenousImaRx Therapeutics, Inc.2007-06-08Not applicableUS flag
Kinlytic (urokinase for Injection)Powder, for solution250000 unit / vialIntravenousMicrobix Biosystems Inc1988-12-312009-10-28Canada flag
Kinlytic Open-cathPowder, for solution5000 unit / vialIntravenousMicrobix Biosystems Inc1991-12-312009-10-28Canada flag

Categories

ATC Codes
B01AD04 — Urokinase
Drug Categories
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
  1. 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]
  2. 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]
  3. FDA Approved Drug Products: Kinlytic Urokinase Injection (Discontinued) [Link]
  4. Health Canada Approved Drug Products: Urokinase Injection [Link]
UniProt
P00749
Genbank
X02419
PubChem Substance
46506299
RxNav
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
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableAneurysmal Subarachnoid Hemorrhage (A-sah) / Cerebral Vasospasm / Hydrocephaly1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableIschemic Stroke1somestatusstop reasonjust information to hide
Not AvailableRecruitingNot AvailableAcute Ischemic Stroke1somestatusstop reasonjust information to hide
Not AvailableUnknown StatusTreatmentVenous Thrombosis (Disorder)1somestatusstop reasonjust information to hide
Not AvailableWithdrawnNot AvailableIschemic Stroke1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Microbix biosystems inc
Packagers
  • Hospira Inc.
  • ImaRx Therapeutics
  • Microbix Biosystems Inc.
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous250000 [iU]/5mL
Powder, for solutionIntravenous250000 unit / vial
Powder, for solutionIntravenous5000 unit / vial
Solution
Injection, powder, lyophilized, for solutionParenteral500000 IU
Injection, powder, for solutionIntravenous100000 IU
Injection, powder, for solutionIntravenous1000000 IU
Injection, powder, for solutionIntravenous25000 IU
Injection, powder, for solutionIntravenous250000 IU
Injection, powder, for solutionIntravenous500000 IU
Injection, powder, for solutionIntravenous bolus; Intravenous drip; Intravitreal100000 IU/2ML
Injection, powder, for solutionIntravenous bolus; Intravenous drip; Intravitreal1000000 IU/5ML
Injection, powder, for solutionIntravenous bolus; Intravenous drip; Intravitreal25000 IU/2ML
Injection, powder, for solutionIntravenous bolus; Intravenous drip; Intravitreal500000 IU/5ML
Injection, powder, for solutionParenteral1000.000 U.I./5ML
Injection, powder, for solutionParenteral250000 U.I./5ML
Injection, powder, for solutionParenteral500000 U.I./5ML
Injection, powder, for solution
Injection, powder, lyophilized, for solutionIntra-arterial; Intravenous250000 iu
Injection, powder, lyophilized, for solutionIntra-arterial; Intravenous500000 iu
Injection, powder, for solutionParenteral
Injection, powder, for solutionIntravenous60000 iu
Injection, powder, for solutionParenteral1000.000 UI
Powder, for solutionIntravenous500000 UI
Powder60000 IU/1vial
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)76 °C at pH 4.5Nowak, U.K. et al., Biochemistry 33:2951-2960 (1994)
hydrophobicity-0.466Not Available
isoelectric point8.66Not Available

Targets

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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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. FDA Approved Drug Products: Kinlytic Urokinase Injection (Discontinued) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inducer
Modulator
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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
Substrate
Inducer
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
  1. 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]
  2. 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]
  3. Hellgren M: Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-30. [Article]
  4. 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]
  5. 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
Substrate
Inducer
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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
  1. 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]
  2. 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]
  3. 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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. 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]
  3. 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]
  4. 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]
  5. 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
  1. 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]
  2. 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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. 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]
  3. 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
  1. 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