Target Information
| Target General Information | Top | |||||
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| Target ID |
T42447
(Former ID: TTDI03159)
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| Target Name |
Doublecortin-like kinase 1 (DCLK1)
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| Synonyms |
Serine/threonine-protein kinase DCLK1; KIAA0369; Doublecortin-like and CAM kinase-like 1; Doublecortin domain-containing protein 3A; DCDC3A; DCAMKL1
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| Gene Name |
DCLK1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
May also participate in functions of the mature nervous system. Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MSFGRDMELEHFDERDKAQRYSRGSRVNGLPSPTHSAHCSFYRTRTLQTLSSEKKAKKVR
FYRNGDRYFKGIVYAISPDRFRSFEALLADLTRTLSDNVNLPQGVRTIYTIDGLKKISSL DQLVEGESYVCGSIEPFKKLEYTKNVNPNWSVNVKTTSASRAVSSLATAKGSPSEVRENK DFIRPKLVTIIRSGVKPRKAVRILLNKKTAHSFEQVLTDITDAIKLDSGVVKRLYTLDGK QVMCLQDFFGDDDIFIACGPEKFRYQDDFLLDESECRVVKSTSYTKIASSSRRSTTKSPG PSRRSKSPASTSSVNGTPGSQLSTPRSGKSPSPSPTSPGSLRKQRSSQHGGSSTSLASTK VCSSMDENDGPGEEVSEEGFQIPATITERYKVGRTIGDGNFAVVKECVERSTAREYALKI IKKSKCRGKEHMIQNEVSILRRVKHPNIVLLIEEMDVPTELYLVMELVKGGDLFDAITST NKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQDGSKSLKLGDFGLATIV DGPLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRGSGDDQEVLFDQ ILMGQVDFPSPYWDNVSDSAKELITMMLLVDVDQRFSAVQVLEHPWVNDDGLPENEHQLS VAGKIKKHFNTGPKPNSTAAGVSVIATTALDKERQVFRRRRNQDVRSRYKAQPAPPELNS ESEDYSPSSSETVRSPNSPF 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: Ruxolitinib | Ligand Info | |||||
| Structure Description | Crystal structure of DCLK1 kinase domain in complex with ruxolitinib | PDB:7F3G | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
SEEGFQIPAT
385 ITERYKVGRT395 IGDGNFAVVK405 ECVERSTARE415 YALKIIKKSK425 CRGKEHMIQN 435 EVSILRRVKH445 PNIVLLIEEM455 DVPTELYLVM465 ELVKGGDLFD475 AITSTNKYTE 485 RDASGMLYNL495 ASAIKYLHSL505 NIVHRDIKPE515 NLLVYEHQDG525 SKSLKLGDFG 535 LATIVDGPLY545 TVCGTPTYVA555 PEIIAETGYG565 LKVDIWAAGV575 ITYILLCGFP 585 PFRGSGDDQE595 VLFDQILMGQ605 VDFPSPYWDN615 VSDSAKELIT625 MMLLVDVDQR 635 FSAVQVLEHP645 WVN
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ILE396
3.518
GLY397
3.557
ASP398
3.728
GLY399
4.215
ALA402
3.982
VAL403
4.574
VAL404
3.527
ALA417
3.348
LYS419
3.685
VAL449
3.336
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| Ligand Name: NVP-TAE684 | Ligand Info | |||||
| Structure Description | Crystal structure of DCLK1-KD in complex with NVP-TAE684 | PDB:5JZN | ||||
| Method | X-ray diffraction | Resolution | 2.85 Å | Mutation | No | [3] |
| PDB Sequence |
GFQIPATITE
388 RYKVGRTIGD398 GNFAVVKECV408 ERSTAREYAL418 KIIKKSKCRG428 KEHMIQNEVS 438 ILRRVKHPNI448 VLLIEEMDVP458 TELYLVMELV468 KGGDLFDAIT478 STNKYTERDA 488 SGMLYNLASA498 IKYLHSLNIV508 HRDIKPENLL518 VYEHQDGSKS528 LKLGDFGLAT 538 IVDGPLYTVC548 GTPTYVAPEI558 IAETGYGLKV568 DIWAAGVITY578 ILLCGFPPFR 588 GSDQEVLFDQ600 ILMGQVDFPS610 PYWDNVSDSA620 KELITMMLLV630 DVDQRFSAVQ 640 VLEHPWVN
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ARG394
4.395
ILE396
3.202
GLY397
3.854
ASP398
4.984
VAL404
3.678
GLU406
3.821
ALA417
3.927
LYS419
3.149
VAL449
4.173
MET465
4.015
GLU466
3.197
LEU467
3.830
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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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| References | Top | |||||
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| REF 1 | Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. Bioorg Med Chem. 2010 Jun 15;18(12):4351-62. | |||||
| REF 2 | Structural Basis of Inhibition of DCLK1 by Ruxolitinib. Int J Mol Sci. 2021 Aug 6;22(16):8488. | |||||
| REF 3 | Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1. Structure. 2016 Sep 6;24(9):1550-61. | |||||
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