Target Information
| Target General Information | Top | |||||
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| Target ID |
T15636
(Former ID: TTDR00588)
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| Target Name |
Tau-tubulin kinase (TTBK1)
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| Synonyms |
Tau-tubulin kinase 1; KIAA1855; Brain-derived tau kinase; BDTK
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| Gene Name |
TTBK1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU.
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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 |
MQCLAAALKDETNMSGGGEQADILPANYVVKDRWKVLKKIGGGGFGEIYEAMDLLTRENV
ALKVESAQQPKQVLKMEVAVLKKLQGKDHVCRFIGCGRNEKFNYVVMQLQGRNLADLRRS QPRGTFTLSTTLRLGKQILESIEAIHSVGFLHRDIKPSNFAMGRLPSTYRKCYMLDFGLA RQYTNTTGDVRPPRNVAGFRGTVRYASVNAHKNREMGRHDDLWSLFYMLVEFAVGQLPWR KIKDKEQVGMIKEKYEHRMLLKHMPSEFHLFLDHIASLDYFTKPDYQLIMSVFENSMKER GIAENEAFDWEKAGTDALLSTSTSTPPQQNTRQTAAMFGVVNVTPVPGDLLRENTEDVLQ GEHLSDQENAPPILPGRPSEGLGPSPHLVPHPGGPEAEVWEETDVNRNKLRINIGKSPCV EEEQSRGMGVPSSPVRAPPDSPTTPVRSLRYRRVNSPESERLSTADGRVELPERRSRMDL PGSPSRQACSSQPAQMLSVDTGHADRQASGRMDVSASVEQEALSNAFRSVPLAEEEDFDS KEWVIIDKETELKDFPPGAEPSTSGTTDEEPEELRPLPEEGEERRRLGAEPTVRPRGRSM QALAEEDLQHLPPQPLPPQLSQGDGRSETSQPPTPGSPSHSPLHSGPRPRRRESDPTGPQ RQVFSVAPPFEVNGLPRAVPLSLPYQDFKRDLSDYRERARLLNRVRRVGFSHMLLTTPQV PLAPVQPQANGKEEEEEEEEDEEEEEEDEEEEEEEEEEEEEEEEEEEEEEEAAAAVALGE VLGPRSGSSSEGSERSTDRSQEGAPSTLLADDQKESRGRASMADGDLEPEEGSKTLVLVS PGDMKKSPVTAELAPDPDLGTLAALTPQHERPQPTGSQLDVSEPGTLSSVLKSEPKPPGP GAGLGAGTVTTGVGGVAVTSSPFTKVERTFVHIAEKTHLNVMSSGGQALRSEEFSAGGEL GLELASDGGAVEEGARAPLENGLALSGLNGAEIEGSALSGAPRETPSEMATNSLPNGPAL ADGPAPVSPLEPSPEKVATISPRRHAMPGSRPRSRIPVLLSEEDTGSEPSGSLSAKERWS KRARPQQDLARLVMEKRQGRLLLRLASGASSSSSEEQRRASETLSGTGSEEDTPASEPAA ALPRKSGRAAATRSRIPRPIGLRMPMPVAAQQPASRSHGAAPALDTAITSRLQLQTPPGS ATAADLRPKQPPGRGLGPGRAQAGARPPAPRSPRLPASTSAARNASASPRSQSLSRRESP SPSHQARPGVPPPRGVPPARAQPDGTPSPGGSKKGPRGKLQAQRATTKGRAGGAEGRAGA R 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: 4-[3-Hydroxyanilino]-6,7-Dimethoxyquinazoline | Ligand Info | |||||
| Structure Description | TTBK1 in complex with inhibitor | PDB:4BTK | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [2] |
| PDB Sequence |
DILPANYVVK
55 DRWKVLKKIG65 GGEIYEAMDL78 LTRENVALKV88 ESAQQPKQVL98 KMEVAVLKKL 108 QGKDHVCRFI118 GCGRNEKFNY128 VVMQLQGRNL138 ADLRRSQPRG148 TFTLSTTLRL 158 GKQILESIEA168 IHSVGFLHRD178 IKPSNFAMGR188 LPSTYRKCYM198 LDFGLARQYT 208 NTTGDVRPPR218 NVAGFRGTVR228 YASVNAHKNR238 EMGRHDDLWS248 LFYMLVEFAV 258 GQLPWRKIKD268 KEQVGMIKEK278 YEHRMLLKHM288 PSEFHLFLDH298 IASLDYFTKP 308 DYQLIMSVFE318 NSMKERGIAE328 NEAFDWE
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| Ligand Name: adenosine diphosphate | Ligand Info | |||||
| Structure Description | TTBK1 in complex with ATP | PDB:4BTJ | ||||
| Method | X-ray diffraction | Resolution | 2.16 Å | Mutation | No | [2] |
| PDB Sequence |
ADILPANYVV
54 KDRWKVLKKI64 GGGGFGEIYE74 AMDLLTRENV84 ALKVESAQQP94 KQVLKMEVAV 104 LKKLQGKDHV114 CRFIGCGRNE124 KFNYVVMQLQ134 GRNLADLRRS144 QPRGTFTLST 154 TLRLGKQILE164 SIEAIHSVGF174 LHRDIKPSNF184 AMGRLPSTYR194 KCYMLDFGLA 204 RQYTNTTGDV214 RPPRNVAGFR224 GTVRYASVNA234 HKNREMGRHD244 DLWSLFYMLV 254 EFAVGQLPWR264 KIKDKEQVGM274 IKEKYEHRML284 LKHMPSEFHL294 FLDHIASLDY 304 FTKPDYQLIM314 SVFENSMKER324 GIAENEAFDW334 EK
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ILE64
3.529
GLY65
3.571
GLY66
3.159
GLY67
4.515
GLY68
3.338
PHE69
4.994
GLY70
4.589
ILE72
3.491
ALA85
3.389
LYS87
2.708
GLU101
4.862
CYS115
3.725
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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 | Tau as a drug target in Alzheimer's disease. J Mol Neurosci. 2002 Dec;19(3):337-8. | |||||
| REF 2 | X-ray structural analysis of tau-tubulin kinase?1 and its interactions with small molecular inhibitors. ChemMedChem. 2013 Nov;8(11):1846-54. | |||||
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