TNIK

TNIK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2X7F, 5CWZ, 5AX9
Identifiers
Aliases	TNIK , TRAF2 and NCK interacting kinase, MRT54
External IDs	OMIM: 610005; MGI: 1916264; HomoloGene: 77943; GeneCards: TNIK; OMA:TNIK - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3q26.2-q26.31 Start 171,058,414 bp [1] End 171,460,408 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3|3 A3 Start 28,317,363 bp [2] End 28,730,007 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte caudate nucleus jejunal mucosa secondary oocyte nucleus accumbens putamen corpus callosum internal globus pallidus duodenum Brodmann area 46 Top expressed in superior cervical ganglion lateral septal nucleus trigeminal ganglion ventromedial nucleus temporal lobe mammillary body lateral hypothalamus superior frontal gyrus amygdala olfactory bulb More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding kinase activity protein serine/threonine kinase activity protein binding ATP binding MAP kinase kinase kinase kinase activity Cellular component cytoplasm recycling endosome endosome nucleoplasm apical plasma membrane extracellular exosome cytoskeleton nucleus cytosol presynapse glutamatergic synapse postsynaptic density, intracellular component Biological process actin cytoskeleton reorganization microvillus assembly positive regulation of protein phosphorylation intracellular signal transduction phosphorylation Wnt signaling pathway nervous system development regulation of dendrite morphogenesis protein phosphorylation cytoskeleton organization protein autophosphorylation protein localization to plasma membrane regulation of mitotic cell cycle regulation of apoptotic process MAPK cascade signal transduction stress-activated protein kinase signaling cascade activation of protein kinase activity neuron projection morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23043 665113 Ensembl ENSG00000154310 ENSMUSG00000027692 UniProt Q9UKE5 P83510 RefSeq (mRNA) NM_001161560 NM_001161561 NM_001161562 NM_001161563 NM_001161564 NM_001161565 NM_001161566 NM_015028 NM_001163007 NM_001163008 NM_001163009 NM_026910 RefSeq (protein) NP_001155032 NP_001155033 NP_001155034 NP_001155035 NP_001155036 NP_001155037 NP_001155038 NP_055843 NP_001156479 NP_001156480 NP_001156481 NP_081186 Location (UCSC) Chr 3: 171.06 – 171.46 Mb Chr 3: 28.32 – 28.73 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

TRAF2 and NCK-interacting protein kinase is an enzyme that in humans is encoded by the TNIK gene. ^{[5] [6] [7]} TNIK is involved in various cellular processes, including signal transduction, gene transcription, and cytoskeletal organization. As an emerging area of therapeutic research, TNIK inhibitors have shown potential in addressing a range of diseases, including cancer, neurological disorders, and inflammatory conditions. ^{[8] [9] [10]}

Structure

Germinal center kinases (GCKs), such as TNIK, are characterized by an N-terminal kinase domain and a C-terminal GCK domain that serves a regulatory function. ^{[6] [7]}

Function

TNIK is a serine/threonine kinase that plays a central role in diverse cellular processes, most notably as a key regulator of the Wnt signaling pathway. ^[11] TNIK is recruited to the promoters of Wnt target genes where it interacts with both β-catenin and TCF4; it phosphorylates TCF4 to enable TCF/LEF-dependent transcriptional activation of Wnt target genes, a function critical for cell proliferation and stem cell maintenance, especially in intestinal and cancerous tissues. ^[11]

Interactions

TNIK has been shown to interact with KIAA0090, ^[12] although the significance is unclear. TNIK has been shown to phosphorylate Gelsolin, a protein involved in F-actin depolymerisation thus inducing cytoskeletal changes. ^[6]

Clinical significance

TNIK plays an important role in pulmonary fibrosis. TNIK inhibitors are used in the treatment of pulmonary fibrosis. ^[9] TNIK has increasingly been of interest in research into the biology of ageing. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000154310 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027692 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, et al. (Aug 1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (1): 31–39. doi: 10.1093/dnares/5.1.31 . PMID   9628581.
6. Fu CA, Shen M, Huang BC, Lasaga J, Payan DG, Luo Y (Nov 1999). "TNIK, a novel member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and regulates the cytoskeleton". Journal of Biological Chemistry. 274 (43): 30729–30737. doi: 10.1074/jbc.274.43.30729 . PMID   10521462.
7. "Entrez Gene: TNIK TRAF2 and NCK interacting kinase".
8. Yamada T, Masuda M (May 2017). "Emergence of TNIK inhibitors in cancer therapeutics". Cancer Science. 108 (5): 818–823. doi:10.1111/cas.13203. PMC   5448614 . PMID   28208209.
9. Garneau-Tsodikova S, Thannickal VJ (2008). "Protein kinase inhibitors in the treatment of pulmonary fibrosis". Current Medicinal Chemistry. 15 (25): 2632–2640. doi:10.2174/092986708785908969. ISSN   0929-8673. PMID   18855683.
10. Ewald CY, Pulous FE, Lok SW, Pun FW, Aliper A, Ren F, et al. (June 2024). "TNIK's emerging role in cancer, metabolism, and age-related diseases". Trends in Pharmacological Sciences. 45 (6): 478–489. doi:10.1016/j.tips.2024.04.010. hdl: 20.500.11850/677315 . PMID   38777670.
11. Mahmoudi T, Li VS, Ng SS, Taouatas N, Vries RG, Mohammed S, et al. (November 2009). "The kinase TNIK is an essential activator of Wnt target genes". The EMBO Journal. 28 (21): 3329–40. doi:10.1038/emboj.2009.285. PMC   2776109 . PMID   19816403.
12. Prieto C, De Las Rivas J (July 2006). "APID: Agile Protein Interaction DataAnalyzer". Nucleic Acids Research. 34 (Web Server issue): W298 –W302. doi:10.1093/nar/gkl128. PMC   1538863 . PMID   16845013. Archived from the original on 2010-04-09.
13. Ewald CY, Pulous FE, Lok SW, Pun FW, Aliper A, Ren F, et al. (June 1, 2024). "TNIK's emerging role in cancer, metabolism, and age-related diseases". Trends in Pharmacological Sciences. 45 (6): 478–489. doi:10.1016/j.tips.2024.04.010. hdl: 20.500.11850/677315 . PMID   38777670 – via www.cell.com.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi: 10.1093/dnares/9.3.99 . PMID   12168954.
• Yonekura H, Migita H, Sakurai S, Wang H, Harada S, Abedin MJ, et al. (Jul 1999). "Antisense display--a method for functional gene screening: evaluation in a cell-free system and isolation of angiogenesis-related genes". Nucleic Acids Research. 27 (13): 2591–2600. doi:10.1093/nar/27.13.2591. PMC   148466 . PMID   10373574.
• Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC (May 2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Analytical Chemistry. 76 (10): 2763–2772. doi:10.1021/ac035352d. PMID   15144186.
• Taira K, Umikawa M, Takei K, Myagmar BE, Shinzato M, Machida N, et al. (Nov 2004). "The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton". Journal of Biological Chemistry. 279 (47): 49488–49496. doi: 10.1074/jbc.M406370200 . PMID   15342639.
• Wissing J, Jansch L, Nimtz M, Dieterich G, Hornberger R, Keri G, et al. (Mar 2007). "Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry". Molecular & Cellular Proteomics. 6 (3): 537–547. doi: 10.1074/mcp.T600062-MCP200 . hdl: 10033/19756 . PMID   17192257.