Target Information
| Target General Information | Top | |||||
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| Target ID |
T98225
(Former ID: TTDI03105)
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| Target Name |
CDC-like kinase 4 (CLK4)
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| Synonyms |
Dual specificity protein kinase CLK4
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| Gene Name |
CLK4
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.12.1
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| Sequence |
MRHSKRTHCPDWDSRESWGHESYRGSHKRKRRSHSSTQENRHCKPHHQFKESDCHYLEAR
SLNERDYRDRRYVDEYRNDYCEGYVPRHYHRDIESGYRIHCSKSSVRSRRSSPKRKRNRH CSSHQSRSKSHRRKRSRSIEDDEEGHLICQSGDVLRARYEIVDTLGEGAFGKVVECIDHG MDGMHVAVKIVKNVGRYREAARSEIQVLEHLNSTDPNSVFRCVQMLEWFDHHGHVCIVFE LLGLSTYDFIKENSFLPFQIDHIRQMAYQICQSINFLHHNKLTHTDLKPENILFVKSDYV VKYNSKMKRDERTLKNTDIKVVDFGSATYDDEHHSTLVSTRHYRAPEVILALGWSQPCDV WSIGCILIEYYLGFTVFQTHDSKEHLAMMERILGPIPQHMIQKTRKRKYFHHNQLDWDEH SSAGRYVRRRCKPLKEFMLCHDEEHEKLFDLVRRMLEYDPTQRITLDEALQHPFFDLLKK K Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| 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: CX-4945 | Ligand Info | |||||
| Structure Description | X-RAY STRUCTURE OF CLK4-KD(146-480)/CX-4945 AT 2.46A | PDB:6FYV | ||||
| Method | X-ray diffraction | Resolution | 2.46 Å | Mutation | No | [2] |
| PDB Sequence |
ICQSGDVLRA
159 RYEIVDTLGE169 GAFGKVVECI179 DHGMDGMHVA189 VKIVKNVGRY199 REAARSEIQV 209 LEHLNSTDPN219 SVFRCVQMLE229 WFDHHGHVCI239 VFELLGLSTY249 DFIKENSFLP 259 FQIDHIRQMA269 YQICQSINFL279 HHNKLTHTDL289 KPENILFVKS299 DYVVKYNKRD 312 ERTLKNTDIK322 VVDFGSATYD332 DEHHSTLVST342 RHYRAPEVIL352 ALGWSQPCDV 362 WSIGCILIEY372 YLGFTVFQTH382 DSKEHLAMME392 RILGPIPQHM402 IQKTRKRKYF 412 HHNQLDWDEH422 SSAGRYVRRR432 CKPLKEFMLC442 HDEEHEKLFD452 LVRRMLEYDP 462 TQRITLDEAL472 QHPFFDLLK
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LEU167
3.480
GLY168
3.482
GLU169
3.477
GLY170
4.344
PHE172
3.368
VAL175
3.756
ALA189
3.512
LYS191
2.788
GLU206
3.794
VAL225
4.140
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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).
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
Biological Network Descriptors
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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| References | Top | |||||
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| REF 1 | Small-molecule pyrimidine inhibitors of the cdc2-like (Clk) and dual specificity tyrosine phosphorylation-regulated (Dyrk) kinases: development of chemical probe ML315. Bioorg Med Chem Lett. 2013 Jun15;23(12):3654-61. | |||||
| REF 2 | X-ray Structures and Feasibility Assessment of CLK2 Inhibitors for Phelan-McDermid Syndrome. ChemMedChem. 2018 Sep 19;13(18):1997-2007. | |||||
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