Target Information
| Target General Information | Top | |||||
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| Target ID |
T72534
(Former ID: TTDI03585)
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| Target Name |
TRAF2 and NCK interacting kinase (TNIK)
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| Synonyms |
TRAF2 and NCK-interacting protein kinase; KIAA0551
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| Gene Name |
TNIK
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322.
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| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
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| Sequence |
MASDSPARSLDEIDLSALRDPAGIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTG
DEEEEIKQEINMLKKYSHHRNIATYYGAFIKKNPPGMDDQLWLVMEFCGAGSVTDLIKNT KGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR TVGRRNTFIGTPYWMAPEVIACDENPDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMR ALFLIPRNPAPRLKSKKWSKKFQSFIESCLVKNHSQRPATEQLMKHPFIRDQPNERQVRI QLKDHIDRTKKKRGEKDETEYEYSGSEEEEEENDSGEPSSILNLPGESTLRRDFLRLQLA NKERSEALRRQQLEQQQRENEEHKRQLLAERQKRIEEQKEQRRRLEEQQRREKELRKQQE REQRRHYEEQMRREEERRRAEHEQEYIRRQLEEEQRQLEILQQQLLHEQALLLEYKRKQL EEQRQAERLQRQLKQERDYLVSLQHQRQEQRPVEKKPLYHYKEGMSPSEKPAWAKEVEER SRLNRQSSPAMPHKVANRISDPNLPPRSESFSISGVQPARTPPMLRPVDPQIPHLVAVKS QGPALTASQSVHEQPTKGLSGFQEALNVTSHRVEMPRQNSDPTSENPPLPTRIEKFDRSS WLRQEEDIPPKVPQRTTSISPALARKNSPGNGSALGPRLGSQPIRASNPDLRRTEPILES PLQRTSSGSSSSSSTPSSQPSSQGGSQPGSQAGSSERTRVRANSKSEGSPVLPHEPAKVK PEESRDITRPSRPASYKKAIDEDLTALAKELRELRIEETNRPMKKVTDYSSSSEESESSE EEEEDGESETHDGTVAVSDIPRLIPTGAPGSNEQYNVGMVGTHGLETSHADSFSGSISRE GTLMIRETSGEKKRSGHSDSNGFAGHINLPDLVQQSHSPAGTPTEGLGRVSTHSQEMDSG TEYGMGSSTKASFTPFVDPRVYQTSPTDEDEEDEESSAAALFTSELLRQEQAKLNEARKI SVVNVNPTNIRPHSDTPEIRKYKKRFNSEILCAALWGVNLLVGTENGLMLLDRSGQGKVY NLINRRRFQQMDVLEGLNVLVTISGKKNKLRVYYLSWLRNRILHNDPEVEKKQGWITVGD LEGCIHYKVVKYERIKFLVIALKNAVEIYAWAPKPYHKFMAFKSFADLQHKPLLVDLTVE EGQRLKVIFGSHTGFHVIDVDSGNSYDIYIPSHIQGNITPHAIVILPKTDGMEMLVCYED EGVYVNTYGRITKDVVLQWGEMPTSVAYIHSNQIMGWGEKAIEIRSVETGHLDGVFMHKR AQRLKFLCERNDKVFFASVRSGGSSQVFFMTLNRNSMMNW 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: Phosphonothreonine | Ligand Info | |||||
| Structure Description | Human tnik in complex with compound 9 | PDB:6RA7 | ||||
| Method | X-ray diffraction | Resolution | 1.20 Å | Mutation | No | [2] |
| PDB Sequence |
IDLSALRDPA
22 GIFELVELVG32 NGTYGQVYKG42 RHVKTGQLAA52 IKVMDVTGDE62 EEEIKQEINM 72 LKKYSHHRNI82 ATYYGAFIKK92 NPPGMDDQLW102 LVMEFCGAGS112 VTDLIKNTKG 122 NTLKEEWIAY132 ICREILRGLS142 HLHQHKVIHR152 DIKGQNVLLT162 ENAEVKLVDF 172 GVSAQLDRVG183 RRNFIGTPYW194 MAPEVIACDE204 NPDATYDFKS214 DLWSLGITAI 224 EMAEGAPPLC234 DMHPMRALFL244 IPRNPAPRLK254 SKKWSKKFQS264 FIESCLVKNH 274 SQRPATEQLM284 KHPFIRDQPN294 ERQVRIQLKD304 HIDRTKKKRG314 |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 1,4-Butanediol | Ligand Info | |||||
| Structure Description | Crystal structure of TNIK-thiopeptide TP1 complex | PDB:7XZQ | ||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [3] |
| PDB Sequence |
DEIDLSALRD
20 PAGIFELVEL30 VGNGTYGQVY40 KGRHVKTGQL50 AAIKVMDVTG60 DEEEEIKQEI 70 NMLKKYSHHR80 NIATYYGAFI90 KKNPPGMDDQ100 LWLVMEFCGA110 GSVTDLIKNT 120 KGNTLKEEWI130 AYICREILRG140 LSHLHQHKVI150 HRDIKGQNVL160 LTENAEVKLV 170 DFGVSAQLDR180 VGRRNFIGTP192 YWMAPEVIAC202 DENPDATYDF212 KSDLWSLGIT 222 AIEMAEGAPP232 LCDMHPMRAL242 FLIPRNPAPR252 LKSKKWSKKF262 QSFIESCLVK 272 NHSQRPATEQ282 LMKHPFIRDQ292 PNERQVRIQL302 KDHIDRTK
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THR35
3.093
VAL39
4.562
ALA52
3.175
LYS54
4.504
ALA83
4.239
MET105
3.909
GLU106
2.923
PHE107
3.966
CYS108
3.026
THR124
4.582
GLU127
4.897
LYS155
3.229
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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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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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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| Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 5.19E-04 |
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| Closeness centrality | 2.31E-01 | Radiality | 1.41E+01 | Clustering coefficient | 1.00E-01 |
| Neighborhood connectivity | 6.16E+01 | Topological coefficient | 2.15E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| References | Top | |||||
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| REF 1 | Discovery of 4-phenyl-2-phenylaminopyridine based TNIK inhibitors. Bioorg Med Chem Lett. 2013 Jan 15;23(2):569-73. | |||||
| REF 2 | Tool inhibitors and assays to interrogate the biology of the TRAF2 and NCK interacting kinase | |||||
| REF 3 | De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors. J Am Chem Soc. 2022 Nov 9;144(44):20332-20341. | |||||
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