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  7. Tyrosine-protein kinase TXK

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

Ligand Count 17
NCBI Gene PubMed Count 25
PubMed Score 191.09
PubTator Score 294.26

Knowledge Summary

Patent (50,553)

TINX Plot

  Disease (4)

Disease Target Count P-value
lung carcinoma 2843 1.9e-20
malignant mesothelioma 3232 1.1e-06
osteosarcoma 7950 2.1e-03
Common variable immunodeficiency 101 2.1e-02
Disease Target Count Z-score Confidence
Carcinoma 11493 0.0 0.7

Expression

  Differential Expression (4)

Disease log2 FC p
Common variable immunodeficiency -1.421 2.1e-02
lung carcinoma -1.500 1.9e-20
malignant mesothelioma -1.900 1.1e-06
osteosarcoma -1.760 2.1e-03

Synonym

Accession P42681 Q14220
Symbols RLK
TKL
BTKL
PTK4
PSCTK5

Gene

TXK

  Ortholog (10)

Species Source Disease
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA EggNOG
Inparanoid OMA
OMA EggNOG
Inparanoid OMA EggNOG

 UniProt Keyword (23)

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 GO Function (5)

 GO Component (3)

 GO Process (17)

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 Compartment GO Term (23)

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 IMPC Phenotype (3)

 MGI Phenotype (2)

 GWAS Trait (2)

 HCA RNA Cell Line (47)

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Pathway (7)

PDB (1)

Drug (5)

Structure of dasatinib

dasatinib
pKd 8.68

Structure of ibrutinib

ibrutinib
pIC50 8.70

Structure of dasatinib

dasatinib
pKd 8.68

Structure of acalabrutinib

acalabrutinib
pIC50 6.43

Structure of bosutinib

bosutinib
pIC50 9.52

Ligand (11)

Structure of CHEMBL398422

CHEMBL398422
pIC50 7.55

Structure of CHEMBL249097

CHEMBL249097
pKd 8.00

Structure of CHEMBL3290142

CHEMBL3290142
pIC50 8.72

Structure of CHEMBL3290148

CHEMBL3290148
pIC50 8.85

Structure of CHEMBL249317

CHEMBL249317
pIC50 9.40

Structure of compound 23 [PMID: 17600705]

compound 23 [PMID: 17600705]
pIC50 9.40

Structure of compound 31 [PMID: 24915291]

compound 31 [PMID: 24915291]
pIC50 8.72

Structure of compound 38 [PMID: 24915291]

compound 38 [PMID: 24915291]
pIC50 8.85

Structure of compound 7 [PMID: 22464456]

compound 7 [PMID: 22464456]
pIC50 7.11

Structure of compound 9 [PMID: 26006010]

compound 9 [PMID: 26006010]
pIC50 7.39

Structure of PRN694

PRN694
pIC50 8.85

Gene RIF (8)

AA Sequence 

MILSSYNTIQSVFCCCCCCSVQKRQMRTQISLSTDEELPEKYTQRRRPWLSQLSNKKQSNTGRVQPSKRK      1 - 70
PLPPLPPSEVAEEKIQVKALYDFLPREPCNLALRRAEEYLILEKYNPHWWKARDRLGNEGLIPSNYVTEN     71 - 140
KITNLEIYEWYHRNITRNQAEHLLRQESKEGAFIVRDSRHLGSYTISVFMGARRSTEAAIKHYQIKKNDS    141 - 210
GQWYVAERHAFQSIPELIWYHQHNAAGLMTRLRYPVGLMGSCLPATAGFSYEKWEIDPSELAFIKEIGSG    211 - 280
QFGVVHLGEWRSHIQVAIKAINEGSMSEEDFIEEAKVMMKLSHSKLVQLYGVCIQRKPLYIVTEFMENGC    281 - 350
LLNYLRENKGKLRKEMLLSVCQDICEGMEYLERNGYIHRDLAARNCLVSSTCIVKISDFGMTRYVLDDEY    351 - 420
VSSFGAKFPIKWSPPEVFLFNKYSSKSDVWSFGVLMWEVFTEGKMPFENKSNLQVVEAISEGFRLYRPHL    421 - 490
APMSIYEVMYSCWHEKPEGRPTFAELLRAVTEIAETW                                     491 - 527
//

Text Mined References (28)

PMID Year Title