InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TXK

Summary

InnateDB Protein

IDBP-17238.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TXK

Protein Name

TXK tyrosine kinase

Synonyms

BTKL; PSCTK5; PTK4; RLK; TKL;

Species

Homo sapiens

Ensembl Protein

ENSP00000264316

InnateDB Gene

IDBG-17234 (TXK)

Protein Structure

UniProt Annotation

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:0000269PubMed:10523612, ECO:0000269PubMed:11564877, ECO:0000269PubMed:11859127, ECO:0000269PubMed:17177976, ECO:0000269PubMed:9813138}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:17177976}. Nucleus {ECO:0000269PubMed:17177976}. Cell membrane {ECO:0000269PubMed:17177976}; Peripheral membrane protein {ECO:0000269PubMed: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.

Disease Associations

Tissue Specificity

Expressed in T-cells and some myeloid cell lines. Expressed in Th1/Th0 cells with IFN-gamma-producing potential. {ECO:0000269PubMed:10523612, ECO:0000269PubMed:7951233}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	6 [view]
Protein-Protein	5 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001012	RNA polymerase II regulatory region DNA binding
GO:0004672	protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0001816	cytokine production
GO:0001865	NK T cell differentiation
GO:0002250	adaptive immune response
GO:0006351	transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006468	protein phosphorylation
GO:0007202	activation of phospholipase C activity
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0032609	interferon-gamma production
GO:0032633	interleukin-4 production
GO:0032729	positive regulation of interferon-gamma production
GO:0046777	protein autophosphorylation
GO:0050852	T cell receptor signaling pathway
GO:0060335	positive regulation of interferon-gamma-mediated signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001452 SH3 domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF00017
PF14633
PF07714
PF00018
PF14604

PRINTS

PR00401
PR00109
PR00452

PIRSF

SMART

SM00252
SM00326
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt