TRAF2 & NCK-interacting protein kinase (TNIK, KIAA0551)
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Function
- serine/threonine protein kinase
- activates Wnt signaling pathway
- recruited to promoters of Wnt target genes & 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 & TNIK which regulates neuronal dendrite extension & arborization during development
- more generally, it may play a role in cytoskeletal rearrangements & regulate cell spreading
- phosphorylates SMAD1 on Thr-322
- autophosphorylated
- autophosphorylation is induced by RAP2A & results in association with the cytoskeletal fraction
- interacts (via the CNH domain) with RAP2A (GTP-bound form preferentially)
- interaction is required for activation of TNIK by RAP2A
- interacts with NEDD4; recruits RAP2A to NEDD4
- interacts with TRAF2 & NCK
- interacts with TCF7L2/TCF4 & CTNNB1
- interacts with TANC1
Structure
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily
- contains 1 CNH domain
- contains 1 protein kinase domain
Compartment
- nucleus, cytoplasm, recycling endosome, cytoskeleton
- associated with recycling endosomes & the cytoskeletal upon RAP2A overexpression
Alternative splicing
named isoforms=8
Expression
- expressed ubiquitously
- highest levels observed in heart, brain & skeletal muscle
- expressed in normal colonic epithelia & colorectal carcinoma tissue
Pathology
- a small molecule inhibitor of TNIK has antifibrotic properties across different organs[2]
More general terms
Additional terms
- nck adaptor protein
- TNF receptor-associated factor 2; tumor necrosis factor type 2 receptor-associated protein 3 (TRAF2, TRAP3)
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q9UKE5.html
- ↑ 2.0 2.1 Ren F, Aliper A, Chen J et al A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models. Nat Biotechnol 2024. March 8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38459338 https://www.nature.com/articles/s41587-024-02143-0