Tchem TXK Tyrosine-protein kinase TXK

Protein Summary

Description

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.

Uniprot Accession IDs

• P42681
• Q14220

Gene Name

• TXK

Ensembl ID

• ENST00000264316
• ENSP00000264316
• ENSG00000074966

Symbol

• PTK4
• RLK
• RLK
• TKL
• BTKL
• PTK4
• PSCTK5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	0.97
biological process	0.95
tissue sample	0.66
disease perturbation	0.62

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Tec Family / Tyrosine-protein Kinase Txk

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 446.77   (req: < 5)

Gene RIFs: 7   (req: <= 3)

Antibodies: 244   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 446.77   (req: >= 5)

Gene RIFs: 7   (req: > 3)

Antibodies: 244   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 37

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 6