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MGP003225

UniProt Annotations

Entry Information

Gene Name	TXK tyrosine kinase
Protein Entry	TXK_HUMAN
UniProt ID	P42681
Species	Human

Comments

Comment type	Description
Catalytic Activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255\|PROSITE- ProRule:PRU10028}.
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. {ECO:0000305}.
Enzyme Regulation	Activated by phosphorylation by FYN. {ECO:0000269\|PubMed:12081135}.
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 cytoskeleton. 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. {ECO:0000269\|PubMed:10523612, ECO:0000269\|PubMed:11564877, ECO:0000269\|PubMed:11859127, ECO:0000269\|PubMed:17177976, ECO:0000269\|PubMed:9813138}.
Interaction	P10721:KIT; NbExp=3; IntAct=EBI-7877438, EBI-1379503;
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. {ECO:0000269\|PubMed:12081135}.
Ptm	The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location. {ECO:0000250}.
Similarity	Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Similarity	Contains 1 SH2 domain. {ECO:0000255\|PROSITE- ProRule:PRU00191}.
Similarity	Contains 1 SH3 domain. {ECO:0000255\|PROSITE- ProRule:PRU00192}.
Subcellular Location	Cytoplasm {ECO:0000269\|PubMed:17177976}. Nucleus {ECO:0000269\|PubMed:17177976}. Cell membrane {ECO:0000269\|PubMed:17177976}; Peripheral membrane protein {ECO:0000269\|PubMed:17177976}. 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.
Subunit	Interacts with PARP1 and EEF1A1. Interacts with SH2D2A (By similarity). {ECO:0000250}.
Tissue Specificity	Expressed in T-cells and some myeloid cell lines. Expressed in Th1/Th0 cells with IFN-gamma-producing potential. {ECO:0000269\|PubMed:10523612, ECO:0000269\|PubMed:7951233}.