Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TXK (P42681) - Overview - Molecular Target Synopsis

Protein


TXK, Tyrosine-protein kinase TXK
Enzyme Classification 2.7.10.2
UniProt P42681

Also Known as TXK_HUMAN, TXK, PTK4, RLK

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. Interacts with PARP1 and EEF1A1. Interacts with SH2D2A.

2DM0
SOLUTION STRUCTURE OF THE SH2 DOMAIN OF HUMAN TYROSINE- PROTEIN KINASE TXK
RCSB/PDB
Inspect Structure
See all 3D Structures for TXK

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: TXK is active in the following subcellular-locations: cell membrane, cytoplasm, nucleus.
GO terms: TXK is active in the following subcellular-locations: cytoplasm, nucleus, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TXK has gain in 1 cell-lines, loss in 4 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, HL_60, NCI_H460

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: DOR 13, SK-MEL-24, Panc 03.27

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


For TXK there are:
1 structures (1 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TXK has been screened with 675 compounds (1262 bioactivities), 30 compounds have bioactivities that show binding affinity of <= 500nM (35 bioactivities). (see details)