TNIK
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. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443).
Involvement in disease
Intellectual developmental disorder, autosomal recessive 54
MRT54
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT54 patients manifest intellectual disability, delayed speech and hyperactivity.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autophosphorylated. Autophosphorylation is activated by RAP2A and induces association to the cytoskeletal fraction.
Sequence Similarities
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Tissue Specificity
Expressed ubiquitously. Highest levels observed in heart, brain and skeletal muscle. Expressed in normal colonic epithelia and colorectal cancer tissues.
Cellular localization
- Nucleus
- Cytoplasm
- Recycling endosome
- Cytoplasm
- Cytoskeleton
- Associated with recycling endosomes and the cytoskeletal fraction upon RAP2A overexpression.
Alternative names
KIAA0551, TNIK, TRAF2 and NCK-interacting protein kinase