| Tchem | Tyrosine-protein kinase TXK |
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.
Comments
Property Summary
| NCBI Gene PubMed Count | 25 |
| Grant Count | 36 |
| R01 Count | 18 |
| Funding | $4,904,944.91 |
| PubMed Score | 168.17 |
| PubTator Score | 294.26 |
| Disease | log2 FC | p |
|---|---|---|
| malignant mesothelioma | -1.900 | 0.000 |
| osteosarcoma | -1.760 | 0.002 |
| Common variable immunodeficiency | -1.421 | 0.021 |
| lung carcinoma | -1.500 | 0.000 |
CHEMBL398422
pIC50 7.55
CHEMBL249097
pKd 8.00
CHEMBL3290142
pIC50 8.72
CHEMBL3290148
pIC50 8.85
CHEMBL249317
pIC50 9.40
| PMID | Text |
|---|---|
| 25593320 | These data indicate that PRN694 is a highly selective and potent covalent inhibitor of ITK and RLK, and its extended target residence time enables durable attenuation of effector cells in vitro and in vivo. |
| 20800603 | Observational study of gene-disease association. (HuGE Navigator) |
| 20628086 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) |
| 20379614 | Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator) |
| 19913121 | Observational study of gene-disease association. (HuGE Navigator) |
| 18941202 | Itk and Txk exert their effects on T helper (Th) cell differentiation and function at the level of expression; transgenic Txk is not a specific regulator of Th1 responses. |
| 16809408 | Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with Behcet's disease. |
| 11859127 | fuctions as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription |
MILSSYNTIQSVFCCCCCCSVQKRQMRTQISLSTDEELPEKYTQRRRPWLSQLSNKKQSNTGRVQPSKRK 1 - 70 PLPPLPPSEVAEEKIQVKALYDFLPREPCNLALRRAEEYLILEKYNPHWWKARDRLGNEGLIPSNYVTEN 71 - 140 KITNLEIYEWYHRNITRNQAEHLLRQESKEGAFIVRDSRHLGSYTISVFMGARRSTEAAIKHYQIKKNDS 141 - 210 GQWYVAERHAFQSIPELIWYHQHNAAGLMTRLRYPVGLMGSCLPATAGFSYEKWEIDPSELAFIKEIGSG 211 - 280 QFGVVHLGEWRSHIQVAIKAINEGSMSEEDFIEEAKVMMKLSHSKLVQLYGVCIQRKPLYIVTEFMENGC 281 - 350 LLNYLRENKGKLRKEMLLSVCQDICEGMEYLERNGYIHRDLAARNCLVSSTCIVKISDFGMTRYVLDDEY 351 - 420 VSSFGAKFPIKWSPPEVFLFNKYSSKSDVWSFGVLMWEVFTEGKMPFENKSNLQVVEAISEGFRLYRPHL 421 - 490 APMSIYEVMYSCWHEKPEGRPTFAELLRAVTEIAETW 491 - 527 //
| PMID | Year | Title |
|---|---|---|
| 25593320 | 2015 | Targeting interleukin-2-inducible T-cell kinase (ITK) and resting lymphocyte kinase (RLK) using a novel covalent inhibitor PRN694. |
| 24728074 | 2014 | Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome. |
| 23128233 | 2012 | Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. |
| 20800603 | 2010 | Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. |
| 20379614 | Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. | |
| 19913121 | 2009 | Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. |
| 19290923 | 2009 | Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk. |
| 18941202 | 2008 | Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses. |
| 17344846 | 2007 | Patterns of somatic mutation in human cancer genomes. |
| More... |
