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TRAF2 & NCK-interacting protein kinase (TNIK, KIAA0551)

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]

Related

nck adaptor protein TNF receptor-associated factor 2; tumor necrosis factor type 2 receptor-associated protein 3 (TRAF2, TRAP3)

General

nuclear protein serine/threonine kinase

Properties

SIZE: entity length = 1360 aa MW = 155 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: kinase domain SITE: 25-289 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 31-39 ATP-binding site NAME: ATP-binding site SITE: 54-54 aspartate residue {D153} Mediates interaction with NEDD4 {290-1047} MOTIF: Thr phosphorylation site {T319} Tyr phosphorylation site {Y321} Tyr phosphorylation site {Y323} Ser phosphorylation site {S324} Ser phosphorylation site {S326} Ser phosphorylation site {S335} Ser phosphorylation site {S560} Thr phosphorylation site {T581} Ser phosphorylation site {S640} Thr phosphorylation site {T677} Ser phosphorylation site {S678} Ser phosphorylation site {S680} Ser phosphorylation site {S688} Ser phosphorylation site {S707} Ser phosphorylation site {S720} Ser phosphorylation site {S726} Ser phosphorylation site {S755} Ser phosphorylation site {S764} Ser phosphorylation site {S766} Ser phosphorylation site {S769} Ser phosphorylation site {S830} Ser phosphorylation site {S831} Ser phosphorylation site {S832} Ser phosphorylation site {S833} Ser phosphorylation site {S838} Ser phosphorylation site {S839} Ser phosphorylation site {S951} Tyr phosphorylation site {Y982} Thr phosphorylation site {T987} Thr phosphorylation site {T1036} CNH {1047-1334} STATE: active state

Database Correlations

OMIM 610005 UniProt Q9UKE5 PFAM correlations Entrez Gene 23043 Kegg hsa:23043 ENZYME 2.7.11.1

References

  1. UniProt :accession Q9UKE5
  2. 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: 38459338 https://www.nature.com/articles/s41587-024-02143-0