Target Information
| Target General Information | Top | |||||
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| Target ID |
T21585
(Former ID: TTDI03104)
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| Target Name |
CDC-like kinase 3 (CLK3)
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| Synonyms |
Dual specificity protein kinase CLK3
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| Gene Name |
CLK3
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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. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. 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 |
MPVLSARRRELADHAGSGRRSGPSPTARSGPHLSALRAQPARAAHLSGRGTYVRRDTAGG
GPGQARPLGPPGTSLLGRGARRSGEGWCPGAFESGARAARPPSRVEPRLATAASREGAGL PRAEVAAGSGRGARSGEWGLAAAGAWETMHHCKRYRSPEPDPYLSYRWKRRRSYSREHEG RLRYPSRREPPPRRSRSRSHDRLPYQRRYRERRDSDTYRCEERSPSFGEDYYGPSRSRHR RRSRERGPYRTRKHAHHCHKRRTRSCSSASSRSQQSSKRSSRSVEDDKEGHLVCRIGDWL QERYEIVGNLGEGTFGKVVECLDHARGKSQVALKIIRNVGKYREAARLEINVLKKIKEKD KENKFLCVLMSDWFNFHGHMCIAFELLGKNTFEFLKENNFQPYPLPHVRHMAYQLCHALR FLHENQLTHTDLKPENILFVNSEFETLYNEHKSCEEKSVKNTSIRVADFGSATFDHEHHT TIVATRHYRPPEVILELGWAQPCDVWSIGCILFEYYRGFTLFQTHENREHLVMMEKILGP IPSHMIHRTRKQKYFYKGGLVWDENSSDGRYVKENCKPLKSYMLQDSLEHVQLFDLMRRM LEFDPAQRITLAEALLHPFFAGLTPEERSFHTSRNPSR 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 CLK3-KD(GP-[275-632], NON-PHOS.)/CX-4945 AT 2.29A | PDB:6FYP | ||||
| Method | X-ray diffraction | Resolution | 2.29 Å | Mutation | No | [3] |
| PDB Sequence |
SVEDDKEGHL
144 VCRIGDWLQE154 RYEIVGNLGE164 GTFGKVVECL174 DHARGKSQVA184 LKIIRNVGKY 194 REAARLEINV204 LKKIKEKDKE214 NKFLCVLMSD224 WFNFHGHMCI234 AFELLGKNTF 244 EFLKENNFQP254 YPLPHVRHMA264 YQLCHALRFL274 HENQLTHTDL284 KPENILFVNS 294 EFETLYNEHK304 SCEEKSVKNT314 SIRVADFGSA324 TFDHEHHTTI334 VATRHYRPPE 344 VILELGWAQP354 CDVWSIGCIL364 FEYYRGFTLF374 QTHENREHLV384 MMEKILGPIP 394 SHMIHRTRKQ404 KYFYKGGLVW414 DENSSDGRYV424 KENCKPLKSY434 MLQDSLEHVQ 444 LFDLMRRMLE454 FDPAQRITLA464 EALLHPFFAG474 LTPEERSF
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LEU162
3.483
GLY163
3.714
GLU164
3.514
GLY165
4.261
PHE167
3.454
VAL170
3.760
ALA184
3.275
LYS186
2.755
GLU201
4.503
VAL220
3.853
PHE236
3.484
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Cdk1/2 inhibitor III | Ligand Info | |||||
| Structure Description | Crystal Structure of the Human CLK3 in complex with DKI | PDB:2WU6 | ||||
| Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [1] |
| PDB Sequence |
RSVEDDKEGH
143 LVCRIGDWLQ153 ERYEIVGNLG163 EGTFGKVVEC173 LDHARGKSQV183 ALKIIRNVGK 193 YREAARLEIN203 VLKKIKEKDK213 ENKFLCVLMS223 DWFNFHGHMC233 IAFELLGKNT 243 FEFLKENNFQ253 PYPLPHVRHM263 AYQLCHALRF273 LHENQLTHTD283 LKPENILFVN 293 SEFETLYNEH303 KSCEEKSVKN313 TSIRVADFGS323 ATFDHEHHTT333 IVATRHYRPP 343 EVILELGWAQ353 PCDVWSIGCI363 LFEYYRGFTL373 FQTHENREHL383 VMMEKILGPI 393 PSHMIHRTRK403 QKYFYKGGLV413 WDENSSDGRY423 VKENCKPLKS433 YMLQDSLEHV 443 QLFDLMRRML453 EFDPAQRITL463 AEALLHPFFA473 GLTPEERSFH483 |
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ASN161
4.255
LEU162
2.837
GLY163
4.927
PHE167
4.678
VAL170
3.258
ALA184
3.430
LYS186
4.155
VAL220
3.637
PHE236
3.560
GLU237
2.919
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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 Similarity Proteins
Human Tissue Distribution
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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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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing. Chem Biol. 2011 Jan 28;18(1):67-76. | |||||
| REF 2 | Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem. 2011 Jun 23;54(12):4172-86. | |||||
| REF 3 | 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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