Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TNIK (Q9UKE5) - Overview - Molecular Target Synopsis

Protein


TNIK, TRAF2 and NCK-interacting protein kinase
Enzyme Classification 2.7.11.1
UniProt Q9UKE5

Also Known as TNIK_HUMAN, TNIK, KIAA0551

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. Interacts (via the CNH domain) with RAP2A (GTP-bound form preferentially); the interaction is direct and required for the activation of TNIK by RAP2A. Interacts with NEDD4; recruits RAP2A to NEDD4. Interacts with TRAF2 and NCK. Interacts with TCF7L2/TCF4 and CTNNB1; the interaction is direct. Interacts with TANC1.

5D7A
CRYSTAL STRUCTURE OF THE KINASE DOMAIN OF TRAF2 AND NCK-INTERACTING PROTEIN KINASE WITH NCB-0846
RCSB/PDB
Inspect Structure
See all 3D Structures for TNIK

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: TNIK is active in the following subcellular-locations: cytoplasm, cytoskeleton, nucleus, recycling endosome.
GO terms: TNIK is active in the following subcellular-locations: apical plasma membrane, cytoplasm, cytoskeleton, cytosol, extracellular exosome, glutamatergic synapse, nucleoplasm, nucleus, postsynaptic density, presynapse, recycling endosome.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TNIK has gain in 17 cell-lines, loss in 0 cell-lines and no signal in 988 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: U251, SK_MEL_28, COLO205

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H446, NCI-H2198, Panc 03.27

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, NHLF

(see details)

RNA Interference


TNIK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OE19, TE6. (see details)

3D Structures


For TNIK there are:
4 structures (14 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TNIK has been screened with 415 compounds (548 bioactivities), 135 compounds have bioactivities that show binding affinity of <= 500nM (160 bioactivities). (see details)