TISIDB

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
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 projection, ruffle. Membrane Note=Colocalizes with KHDRBS1, KHDRBS2 or KHDRBS3, within the nucleus. Nuclear localization in epithelial cells of normal prostate but cytoplasmic localization in cancer prostate.
Domain	PF07714 Protein tyrosine kinase PF00017 SH2 domain PF00018 SH3 domain
Function	Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.; FUNCTION: Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins.

> Gene Ontology [ TOP ]
Biological Process	GO:0001101 response to acid chemical GO:0001933 negative regulation of protein phosphorylation GO:0002065 columnar/cuboidal epithelial cell differentiation GO:0006469 negative regulation of protein kinase activity GO:0007173 epidermal growth factor receptor signaling pathway GO:0007259 JAK-STAT cascade GO:0007260 tyrosine phosphorylation of STAT protein GO:0010720 positive regulation of cell development GO:0010975 regulation of neuron projection development GO:0010976 positive regulation of neuron projection development GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0031346 positive regulation of cell projection organization GO:0032526 response to retinoic acid GO:0033673 negative regulation of kinase activity GO:0038083 peptidyl-tyrosine autophosphorylation GO:0038127 ERBB signaling pathway GO:0038128 ERBB2 signaling pathway GO:0042058 regulation of epidermal growth factor receptor signaling pathway GO:0042326 negative regulation of phosphorylation GO:0042503 tyrosine phosphorylation of Stat3 protein GO:0042506 tyrosine phosphorylation of Stat5 protein GO:0042509 regulation of tyrosine phosphorylation of STAT protein GO:0042516 regulation of tyrosine phosphorylation of Stat3 protein GO:0042517 positive regulation of tyrosine phosphorylation of Stat3 protein GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein GO:0045666 positive regulation of neuron differentiation GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway GO:0045787 positive regulation of cell cycle GO:0045926 negative regulation of growth GO:0046425 regulation of JAK-STAT cascade GO:0046427 positive regulation of JAK-STAT cascade GO:0046777 protein autophosphorylation GO:0048565 digestive tract development GO:0050730 regulation of peptidyl-tyrosine phosphorylation GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation GO:0050732 negative regulation of peptidyl-tyrosine phosphorylation GO:0050769 positive regulation of neurogenesis GO:0051348 negative regulation of transferase activity GO:0051962 positive regulation of nervous system development GO:0055123 digestive system development GO:0060575 intestinal epithelial cell differentiation GO:0061097 regulation of protein tyrosine kinase activity GO:0061099 negative regulation of protein tyrosine kinase activity GO:0071229 cellular response to acid chemical GO:0071300 cellular response to retinoic acid GO:0071396 cellular response to lipid GO:0097696 STAT cascade GO:1901184 regulation of ERBB signaling pathway GO:1901186 positive regulation of ERBB signaling pathway GO:1904892 regulation of STAT cascade GO:1904894 positive regulation of STAT cascade
Molecular Function	GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity
Cellular Component	GO:0001726 ruffle 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:0031252 cell leading edge GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1640170: Cell Cycle R-HSA-69278: Cell Cycle, Mitotic R-HSA-69656: Cyclin A R-HSA-69202: Cyclin E associated events during G1/S transition R-HSA-8847993: ERBB2 Activates PTK6 Signaling R-HSA-69206: G1/S Transition R-HSA-453279: Mitotic G1-G1/S phases R-HSA-8849474: PTK6 Activates STAT3 R-HSA-8849472: PTK6 Down-Regulation R-HSA-8849473: PTK6 Expression R-HSA-8849470: PTK6 Regulates Cell Cycle R-HSA-8849468: PTK6 Regulates Proteins Involved in RNA Processing R-HSA-8849471: PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases R-HSA-8849469: PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 R-HSA-8857538: PTK6 promotes HIF1A stabilization R-HSA-69242: S Phase R-HSA-187577: SCF(Skp2)-mediated degradation of p27/p21 R-HSA-162582: Signal Transduction R-HSA-1227986: Signaling by ERBB2 R-HSA-8848021: Signaling by PTK6

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-1640170: Cell Cycle
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-69656: Cyclin A
R-HSA-69202: Cyclin E associated events during G1/S transition
R-HSA-8847993: ERBB2 Activates PTK6 Signaling
R-HSA-69206: G1/S Transition
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-8849474: PTK6 Activates STAT3
R-HSA-8849472: PTK6 Down-Regulation
R-HSA-8849473: PTK6 Expression
R-HSA-8849470: PTK6 Regulates Cell Cycle
R-HSA-8849468: PTK6 Regulates Proteins Involved in RNA Processing
R-HSA-8849471: PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases
R-HSA-8849469: PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
R-HSA-8857538: PTK6 promotes HIF1A stabilization
R-HSA-69242: S Phase
R-HSA-187577: SCF(Skp2)-mediated degradation of p27/p21
R-HSA-162582: Signal Transduction
R-HSA-1227986: Signaling by ERBB2
R-HSA-8848021: Signaling by PTK6

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PTK6 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 ]
There is no record.

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
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 PTK6 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	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
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 PTK6 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	0.28	0.61
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.719	0.413
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.02	0.168
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.206	0.739
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.237	0.908
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.151	0.944
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.801	0.215
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.188	0.211
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.449	0.653
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-1.357	0.0369
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	-1.872	0.0265
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.256	0.347

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PTK6 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	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	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	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	9.1	-1.4	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	9.1	0	9.1	0.458
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PTK6. 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	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PTK6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PTK6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PTK6. 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	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PTK6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PTK6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PTK6
Name	protein tyrosine kinase 6
Aliases	BRK; PTK6 protein tyrosine kinase 6; breast tumor kinase; protein-tyrosine kinase BRK; tyrosine-protein kina ......
Chromosomal Location	20q13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PTK6 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PTK6.

ID	Name	Drug Type	Targets	#Targets
DB05294	Vandetanib	Small Molecule	EGFR, PTK6, RET, TEK, VEGFA	5

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