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FLASH GENE
Symbol TNK2 contributors: mct - updated : 26-05-2014
HGNC name tyrosine kinase, non-receptor, 2
HGNC id 19297
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region, with the C-lobe of the kinase domain, and the SH3 domain
  • one CRIB domain
  • C-terminal Mig6 homology region (MHR) (residues 802-990) participates in inhibitory intramolecular interactions , and an SH3 motif and a proline-rich C terminus
  • HOMOLOGY
    interspecies homolog to murine Cos1
    Homologene
    FAMILY
  • Tyr protein kinase family
  • CATEGORY enzyme , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,nucleus
    basic FUNCTION
  • may be involved in a regulatory mechanism that sustains the GTP-bound active form of CDC42 and which is directly linked to a tyrosine phosphorylation signal transduction pathway
  • playing a role in transducing CDC42 signals directly to the nucleus
  • involved in extracellular matrix-induced integrin signaling, ultimately activating signaling processes like the activation of the small GTPase Rac
  • tyrosine kinase linked to many components involved in vesicle dynamics including clathrin, AP2 and synaptojanin-1
  • ability of TNK2 to modulate AXL and perhaps anaplastic lymphoma kinase (altered in anaplastic large cell lymphomas) might explain why TNK2 can promote metastatic and transformed behavior in a number of cancers
  • nonreceptor tyrosine kinase that participates in tumorigenesis, cell survival, and migration
  • by positively regulating pro-survival factors such as AKT and AR, TNK2 is emerging as a critical player in cancer biology
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CDC42
  • interacting with SYNJ1 and SNX9
  • interacting with NPHP1 (TNK2 is a novel interaction partner of nephrocystin-1 and implicate cell-cell junctions and the renal collecting duct in the pathology of nephronophthisis)
  • NEDD4L binds TNK2 via a conserved PPXY-containing region
  • concentrated at clathrin-coated pits, and binds clathrin heavy chain via two clathrin boxes
  • GRB2 mediates the interaction of TNK2 with EGFR through binding to the EBD and activates TNK2 by releasing the auto-inhibition
  • interaction of TNK2 with SIAH1 and the induction of proteasomal degradation of TNK2 by SIAH1 are independent of ACK1 kinase activity
  • required for TNFSF10-induced cell death in multiple epithelial cell lines (PMId: 24085293)
  • is an essential player in the spatial regulation of TNFSR10A, TNFSR10B (PMId: 24085293)
  • cell & other
    REGULATION
    Other is not autoinhibited but requires SRC for activation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cancer cell lines with invasive phenotype
    tumoral   amplification    
    is an independent predictor of a poor prognosis in patients with gastric carcinoma (GC) and leads to an increase in the malignant potential of GC cells
    constitutional germinal mutation      
    in autosomal recessive, infantile onset epilepsy and intellectual disability
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS