Target Information
| Target General Information | Top | |||||
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| Target ID |
T73725
(Former ID: TTDI03103)
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| Target Name |
CDC-like kinase 2 (CLK2)
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| Synonyms |
Dual specificity protein kinase CLK2
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| Gene Name |
CLK2
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| Target Type |
Patented-recorded 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. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, 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 |
MPHPRRYHSSERGSRGSYREHYRSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYD
DRSSDRRVYDRRYCGSYRRNDYSRDRGDAYYDTDYRHSYEYQRENSSYRSQRSSRRKHRR RRRRSRTFSRSSSQHSSRRAKSVEDDAEGHLIYHVGDWLQERYEIVSTLGEGTFGRVVQC VDHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPDNKNLCVQMFDWFDYHGHMC ISFELLGLSTFDFLKDNNYLPYPIHQVRHMAFQLCQAVKFLHDNKLTHTDLKPENILFVN SDYELTYNLEKKRDERSVKSTAVRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQ PCDVWSIGCIIFEYYVGFTLFQTHDNREHLAMMERILGPIPSRMIRKTRKQKYFYRGRLD WDENTSAGRYVRENCKPLRRYLTSEAEEHHQLFDLIESMLEYEPAKRLTLGEALQHPFFA RLRAEPPNKLWDSSRDISR Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| 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 CLK2-KD(136-496)/CX-4945 at 1.95A | PDB:6FYL | ||||
| Method | X-ray diffraction | Resolution | 1.95 Å | Mutation | No | [3] |
| PDB Sequence |
EDDAEGHLIY
153 HVGDWLQERY163 EIVSTLGEGT173 FGRVVQCVDH183 RRGGARVALK193 IIKNVEKYKE 203 AARLEINVLE213 KINEKDPDNK223 NLCVQMFDWF233 DYHGHMCISF243 ELLGLSTFDF 253 LKDNNYLPYP263 IHQVRHMAFQ273 LCQAVKFLHD283 NKLTHTDLKP293 ENILFVNSDY 303 ELTYNLEKKR313 DERSVKSTAV323 RVVDFGSATF333 DHEHHSTIVS343 TRHYRAPEVI 353 LELGWSQPCD363 VWSIGCIIFE373 YYVGFTLFQT383 HDNREHLAMM393 ERILGPIPSR 403 MIRKTRKQKY413 FYRGRLDWDE423 NTSAGRYVRE433 NCKPLRRYLT443 SEAEEHHQLF 453 DLIESMLEYE463 PAKRLTLGEA473 LQHPFFARLR483
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LEU169
3.665
GLY170
3.585
GLU171
3.490
GLY172
3.906
PHE174
3.189
GLY175
4.499
ARG176
4.851
VAL177
3.708
ALA191
3.393
LYS193
3.054
GLU208
4.254
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: TG003 | Ligand Info | |||||
| Structure Description | X-ray Structure of CLK2-KD(130-496)/TG003 at 2.6A | PDB:6FYI | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
EGHLIYHVGD
157 WLQERYEIVS167 TLGEGTFGRV177 VQCVDHRRGG187 ARVALKIIKN197 VEKYKEAARL 207 EINVLEKINE217 KDPDNKNLCV227 QMFDWFDYHG237 HMCISFELLG247 LSTFDFLKDN 257 NYLPYPIHQV267 RHMAFQLCQA277 VKFLHDNKLT287 HTDLKPENIL297 FVNSDYELTY 307 NLEKKRDERS317 VKSTAVRVVD327 FGSATFDHEH337 HSTIVSTRHY347 RAPEVILELG 357 WSQPCDVWSI367 GCIIFEYYVG377 FTLFQTHDNR387 EHLAMMERIL397 GPIPSRMIRK 407 TRKQKYFYRG417 RLDWDENTSA427 GRYVRENCKP437 LRRYLTSEAE447 EHHQLFDLIE 457 SMLEYEPAKR467 LTLGEALQHP477 FFARLR
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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 Similarity Proteins
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| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. | |||||
| REF 2 | 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 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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