Target Information
Target General Information | Top | |||||
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Target ID |
T15882
(Former ID: TTDI02312)
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Target Name |
Leukocyte proteinase-3 (PRTN3)
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Synonyms |
Wegener autoantigen; PR3; PR-3; P29; Neutrophil proteinase 4; NP4; NP-4; Myeloblastin; MBN; Leukocyte proteinase 3; CANCA antigen; C-ANCA antigen; AGP7
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Gene Name |
PRTN3
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
2 | Myocardial infarction [ICD-11: BA41-BA43] | |||||
Function |
By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration. May play a role in neutrophil transendothelial migration, probably when associated with CD177. Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro).
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BioChemical Class |
Peptidase
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UniProt ID | ||||||
EC Number |
EC 3.4.21.76
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Sequence |
MAHRPPSPALASVLLALLLSGAARAAEIVGGHEAQPHSRPYMASLQMRGNPGSHFCGGTL
IHPSFVLTAAHCLRDIPQRLVNVVLGAHNVRTQEPTQQHFSVAQVFLNNYDAENKLNDVL LIQLSSPANLSASVATVQLPQQDQPVPHGTQCLAMGWGRVGAHDPPAQVLQELNVTVVTF FCRPHNICTFVPRRKAGICFGDSGGPLICDGIIQGIDSFVIWGCATRLFPDFFTRVALYV DWIRSTLRRVEAKGRP Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | Combined PR1/WT1 vaccine | Drug Info | Phase 2 | Myeloid leukaemia | [2] | |
2 | Tiprelestat | Drug Info | Phase 2 | Myocardial infarction | [3] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Tiprelestat | Drug Info | [4] | |||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | PMID22595175C4g | Drug Info | [5] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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).
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
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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Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 6.39E-05 |
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Closeness centrality | 1.83E-01 | Radiality | 1.31E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 5.00E+00 | Topological coefficient | 2.11E-01 | 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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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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PID Pathway | [+] 1 PID Pathways | + | ||||
1 | C-MYB transcription factor network | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Common Pathway of Fibrin Clot Formation |
References | Top | |||||
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REF 1 | Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008 Jan 1;111(1):236-42. | |||||
REF 2 | Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies. Front Immunol. 2015 Feb 4;6:36. | |||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021706) | |||||
REF 4 | Company report (Proteo Biotech AG) | |||||
REF 5 | N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3993-7. |
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