TISIDB

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm Nucleus Cell membrane Peripheral membrane protein 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.
Domain	PF07714 Protein tyrosine kinase PF00017 SH2 domain PF00018 SH3 domain
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.

> Gene Ontology [ TOP ]
Biological Process	GO:0001819 positive regulation of cytokine production GO:0001959 regulation of cytokine-mediated signaling pathway GO:0001961 positive regulation of cytokine-mediated signaling pathway GO:0002250 adaptive immune response GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0007202 activation of phospholipase C activity GO:0007229 integrin-mediated signaling pathway GO:0007596 blood coagulation GO:0007599 hemostasis GO:0010517 regulation of phospholipase activity GO:0010518 positive regulation of phospholipase activity GO:0010543 regulation of platelet activation GO:0010863 positive regulation of phospholipase C activity GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0030168 platelet activation GO:0030193 regulation of blood coagulation GO:0031099 regeneration GO:0031349 positive regulation of defense response GO:0032609 interferon-gamma production GO:0032649 regulation of interferon-gamma production GO:0032729 positive regulation of interferon-gamma production GO:0034341 response to interferon-gamma GO:0038083 peptidyl-tyrosine autophosphorylation GO:0042246 tissue regeneration GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0046777 protein autophosphorylation GO:0050817 coagulation GO:0050818 regulation of coagulation GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0050865 regulation of cell activation GO:0050878 regulation of body fluid levels GO:0060191 regulation of lipase activity GO:0060193 positive regulation of lipase activity GO:0060330 regulation of response to interferon-gamma GO:0060332 positive regulation of response to interferon-gamma GO:0060333 interferon-gamma-mediated signaling pathway GO:0060334 regulation of interferon-gamma-mediated signaling pathway GO:0060335 positive regulation of interferon-gamma-mediated signaling pathway GO:0060759 regulation of response to cytokine stimulus GO:0060760 positive regulation of response to cytokine stimulus GO:0061041 regulation of wound healing GO:0071346 cellular response to interferon-gamma GO:1900046 regulation of hemostasis GO:1900274 regulation of phospholipase C activity GO:1903034 regulation of response to wounding
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001159 core promoter proximal region DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity
Cellular Component	GO:0009898 cytoplasmic side of plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04670 Leukocyte transendothelial migration
Reactome	R-HSA-2871809: FCERI mediated Ca+2 mobilization R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TXK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

[ TOP ]

Literatures describing the relation between TXK and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28274958	Prostate Carcinoma	Inhibit immunity (infiltration)	Here, we show that cabozantinib rapidly eradicates invasive, poorly differentiated PTEN/p53-deficient murine prostate cancer. This was associated with enhanced release of neutrophil chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils into the tumor.
27863995	Melanoma	Inhibit immunity (infiltration)	To effectively treat this aggressive tumor, a multi-target receptor tyrosine kinase inhibitor, sunitinib base, was efficiently encapsulated into a targeted polymeric micelle nano-delivery system (SUNb-PM), working in a synergistic manner with vaccine therapy in an advanced mouse melanoma model. SUNb-PM not only increased cytotoxic T-cell infiltration and decreased the number and percentage of MDSCs and Tregs in the TME, but also induced a shift in cytokine expression from Th2 to Th1 type while remodeling the tumor-associated fibroblasts, collagen, and blood vessels in the tumor.
28895560	Acute Myeloid Leukemia	Resistant to immunotherapy	Tyrosine kinase inhibition increases the cell surface localization of FLT3-ITD and enhances FLT3-directed immunotherapy of acute myeloid leukemia. TKI treatment increased the surface expression through upregulation of FLT3 and glycosylation of FLT3-ITD and FLT3-D835Y mutants.

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of TXK in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of TXK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.236	0.206
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.507	0.193
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.035	0.91
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.355	0.4
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.507	0.677
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.164	0.91
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.045	0.923
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.451	0.54
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.305	0.683
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.691	0.413
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.102	0.931
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.006	0.971

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of TXK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	16.7	-4.2	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TXK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TXK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TXK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TXK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TXK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TXK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TXK
Name	TXK tyrosine kinase
Aliases	TKL; PSCTK5; BTKL; RLK; PTK4; PTK4 protein tyrosine kinase 4; protein-tyrosine kinase 4; resting lymphocyte ......
Chromosomal Location	4p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TXK collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse TXK