Target Information
| Target General Information | Top | |||||
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| Target ID |
T44341
(Former ID: TTDI03148)
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| Target Name |
Cyclin-dependent kinase-like 2 (CDKL2)
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| Synonyms |
Serine/threonine-protein kinase KKIAMRE; Protein kinase p56 KKIAMRE
Click to Show/Hide
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| Gene Name |
CDKL2
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
centrosome, nucleus, cyclin-dependent protein serine/threonine kinase activity, protein kinase activity, protein phosphorylation, sex differentiation, signal transduction.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.22
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| Sequence |
MEKYENLGLVGEGSYGMVMKCRNKDTGRIVAIKKFLESDDDKMVKKIAMREIKLLKQLRH
ENLVNLLEVCKKKKRWYLVFEFVDHTILDDLELFPNGLDYQVVQKYLFQIINGIGFCHSH NIIHRDIKPENILVSQSGVVKLCDFGFARTLAAPGEVYTDYVATRWYRAPELLVGDVKYG KAVDVWAIGCLVTEMFMGEPLFPGDSDIDQLYHIMMCLGNLIPRHQELFNKNPVFAGVRL PEIKEREPLERRYPKLSEVVIDLAKKCLHIDPDKRPFCAELLHHDFFQMDGFAERFSQEL QLKVQKDARNVSLSKKSQNRKKEKEKDDSLVEERKTLVVQDTNADPKIKDYKLFKIKGSK IDGEKAEKGNRASNASCLHDSRTSHNKIVPSTSLKDCSNVSVDHTRNPSVAIPPLTHNLS AVAPSINSGMGTETIPIQGYRVDEKTKKCSIPFVKPNRHSPSGIYNINVTTLVSGPPLSD DSGADLPQMEHQH 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: Cdk1/2 inhibitor III | Ligand Info | |||||
| Structure Description | Crystal structure of the human CDKL2 kinase domain | PDB:4AAA | ||||
| Method | X-ray diffraction | Resolution | 1.53 Å | Mutation | Yes | [2] |
| PDB Sequence |
LYFQSMEKYE
5 NLGLVGEGSY15 GMVMKCRNKD25 TGRIVAIKKF35 LESDDDKMVK45 KIAMREIKLL 55 KQLRHENLVN65 LLEVCKKKKR75 WYLVFEFVDH85 TILDDLELFP95 NGLDYQVVQK 105 YLFQIINGIG115 FCHSHNIIHR125 DIKPENILVS135 QSGVVKLCDF145 GFAEVATRWY 167 RAPELLVGDV177 KYGKAVDVWA187 IGCLVTEMFM197 GEPLFPGDSD207 IDQLYHIMMC 217 LGNLIPRHQE227 LFNKNPVFAG237 VRLPEIKERE247 PLERRYPKLS257 EVVIDLAKKC 267 LHIDPDKRPF277 CAELLHHDFF287 QMDGFAERFS297 QELQL
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VAL10
3.363
GLY11
3.207
GLU12
4.618
SER14
4.685
TYR15
3.193
VAL18
3.264
ALA31
3.700
LYS33
4.917
VAL64
3.547
PHE80
3.925
GLU81
2.875
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| Ligand Name: 4'-[5-[[3-[(Cyclopropylamino)methyl]phenyl]amino]-1h-Pyrazol-3-Yl]-[1,1'-Biphenyl]-2,4-Diol | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF THE HUMAN CDKL2 KINASE DOMAIN WITH BOUND TCS 2312 | PDB:4BBM | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | Yes | [2] |
| PDB Sequence |
TENLYFQSME
2 KYENLGLVGS14 YGMVMKCRNK24 DTGRIVAIKK34 FLESDDDKMV44 KKIAMREIKL 54 LKQLRHENLV64 NLLEVCKKKK74 RWYLVFEFVD84 HTILDDLELF94 PNGLDYQVVQ 104 KYLFQIINGI114 GFCHSHNIIH124 RDIKPENILV134 SQSGVVKLCD144 FGFARTLAAP 154 GEVYDDEVAT164 RWYRAPELLV174 GDVKYGKAVD184 VWAIGCLVTE194 MFMGEPLFPG 204 DSDIDQLYHI214 MMCLGNLIPR224 HQELFNKNPV234 FAGVRLPEIK244 EREPLERRYP 254 KLSEVVIDLA264 KKCLHIDPDK274 RPFCAELLHH284 DFFQMDGFAE294 RFSQELQLKV 304 QKDA
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VAL10
3.600
GLY11
4.241
TYR15
3.363
VAL18
3.925
ALA31
3.587
LYS33
4.091
VAL64
3.111
PHE80
3.401
GLU81
3.020
PHE82
3.475
VAL83
3.022
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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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| References | Top | |||||
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| REF 1 | Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem. 2013 Oct 24;56(20):8032-48. | |||||
| REF 2 | CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function. Cell Rep. 2018 Jan 23;22(4):885-894. | |||||
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