ID:TXK_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein kinase TXK; EC=2.7.10.2; AltName: Full=Protein-tyrosine kinase 4; AltName: Full=Resting lymphocyte kinase; FUNCTION: Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T- cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskekleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell- specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr- 201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Activated by phosphorylation by FYN. SUBUNIT: Interacts with PARP1 and EEF1A1. Interacts with SH2D2A (By similarity). SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. Translocates into the nucleus and enhances IFN-gamma gene transcription in T-cells. TISSUE SPECIFICITY: Expressed in T-cells and some myeloid cell lines. Expressed in Th1/Th0 cells with IFN-gamma-producing potential. PTM: Phosphorylated at Tyr-420 by FYN. Autophosphorylation at Tyr- 91 is critical for the activation of TXK, leading to the up- regulation of IFN-gamma gene transcription. PTM: The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. CAUTION: Unlike the other TEC subfamily members, TXK is activated independently of the activity of phosphatidylinositol 3-kinase, consistent with its lack of a PH domain. Membrane association is performed through palmitoylation at the N-terminus.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P42681
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000166 nucleotide binding GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0001012 RNA polymerase II regulatory region DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0004672 protein kinase activity GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0016301 kinase activity GO:0016740 transferase activity GO:0005102 receptor binding
Biological Process: GO:0001816 cytokine production GO:0002250 adaptive immune response GO:0002376 immune system process GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006468 protein phosphorylation GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007202 activation of phospholipase C activity GO:0007229 integrin-mediated signaling pathway GO:0010543 regulation of platelet activation GO:0016310 phosphorylation GO:0030154 cell differentiation GO:0032729 positive regulation of interferon-gamma production GO:0038083 peptidyl-tyrosine autophosphorylation GO:0042127 regulation of cell proliferation GO:0042246 tissue regeneration GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046777 protein autophosphorylation GO:0050852 T cell receptor signaling pathway GO:0060335 positive regulation of interferon-gamma-mediated signaling pathway
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
