Target Information
| Target General Information | Top | |||||
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| Target ID |
T74363
(Former ID: TTDR00369)
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| Target Name |
Urokinase plasminogen activator surface receptor (PLAUR)
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| Synonyms |
Urokinase-type plasminogen activator receptor; Urokinase plasminogen activator receptor; Monocyte activation antigenMo3; CD87 antigen; CD87
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| Gene Name |
PLAUR
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Myeloproliferative neoplasm [ICD-11: 2A20] | |||||
| 2 | Thrombocytosis [ICD-11: 3B63] | |||||
| Function |
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. Acts as a receptor for urokinase plasminogen activator.
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| UniProt ID | ||||||
| Sequence |
MGHPPLLPLLLLLHTCVPASWGLRCMQCKTNGDCRVEECALGQDLCRTTIVRLWEEGEEL
ELVEKSCTHSEKTNRTLSYRTGLKITSLTEVVCGLDLCNQGNSGRAVTYSRSRYLECISC GSSDMSCERGRHQSLQCRSPEEQCLDVVTHWIQEGEEGRPKDDRHLRGCGYLPGCPGSNG FHNNDTFHFLKCCNTTKCNEGPILELENLPQNGRQCYSCKGNSTHGCSSEETFLIDCRGP MNQCLVATGTHEPKNQSYMVRGCATASMCQHAHLGDAFSMNHIDVSCCTKSGCNHPDLDV QYRSGAAPQPGPAHLSLTITLLMTARLWGGTLLWT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T82F70 | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Ruxolitinib | Drug Info | Approved | High-risk myelofibrosis | [2], [3], [4], [5] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Ruxolitinib | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 2-(Acetylamino)-2-Deoxy-a-D-Glucopyranose | Ligand Info | |||||
| Structure Description | Structure of Human Urokinase Plasminogen Activator in Complex with Urokinase Receptor and an anti-upar antibody at 1.9 A | PDB:2FD6 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [6] |
| PDB Sequence |
SLRCMQCKTN
9 GDCRVEECAL19 GQDLCRTTIV29 RLWEELELVE42 KSCTHSEKTN52 RTLSYRTGLK 62 ITSLTEVVCG72 LDLCNQGNYL93 ECISCGSSDM103 SCERGRHQSL113 QCRSPEEQCL 123 DVVTHWDDRH143 LRGCGYLPGC153 PGSNGFHNND163 TFHFLKCCNT173 TKCNEGPILE 183 LENLPQNGRQ193 CYSCKGNSTH203 GCSSEETFLI213 DCRGPMNQCL223 VATGTHEPKN 233 QSYMVRGCAT243 ASMCQLGDAF256 SMNHIDVSCC266 TKSGCNHPD
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| Ligand Name: 2-Ethoxyethanol | Ligand Info | |||||
| Structure Description | Structure of Human Urokinase Plasminogen Activator in Complex with Urokinase Receptor and an anti-upar antibody at 1.9 A | PDB:2FD6 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [6] |
| PDB Sequence |
SLRCMQCKTN
9 GDCRVEECAL19 GQDLCRTTIV29 RLWEELELVE42 KSCTHSEKTN52 RTLSYRTGLK 62 ITSLTEVVCG72 LDLCNQGNYL93 ECISCGSSDM103 SCERGRHQSL113 QCRSPEEQCL 123 DVVTHWDDRH143 LRGCGYLPGC153 PGSNGFHNND163 TFHFLKCCNT173 TKCNEGPILE 183 LENLPQNGRQ193 CYSCKGNSTH203 GCSSEETFLI213 DCRGPMNQCL223 VATGTHEPKN 233 QSYMVRGCAT243 ASMCQLGDAF256 SMNHIDVSCC266 TKSGCNHPD
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Complement and coagulation cascades | hsa04610 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 19 | Degree centrality | 2.04E-03 | Betweenness centrality | 1.28E-03 |
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| Closeness centrality | 2.40E-01 | Radiality | 1.42E+01 | Clustering coefficient | 2.05E-01 |
| Neighborhood connectivity | 3.61E+01 | Topological coefficient | 8.51E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5688). | |||||
| REF 3 | ClinicalTrials.gov (NCT02038036) Ruxolitinib Efficacy and Safety in Patients With HU Resistant or Intolerant Polycythemia Vera vs Best Available Therapy.. U.S. National Institutes of Health. | |||||
| REF 4 | Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. | |||||
| REF 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 6 | Structure of human urokinase plasminogen activator in complex with its receptor. Science. 2006 Feb 3;311(5761):656-9. | |||||
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