PTK6 Gene

HGNC Family	SH2 domain containing
Name	protein tyrosine kinase 6
Description	The protein encoded by this gene is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. The encoded protein has been shown to undergo autophosphorylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein tyrosine kinase 6 (PTK6), also known as breast tumor kinase (Brk), is a non‐receptor tyrosine kinase whose aberrant expression has been documented in a wide range of epithelial cancers including breast, prostate, colon, pancreatic, ovarian, and even esophageal carcinomas. In normal epithelia PTK6 is often localized to the nucleus where it may be involved in differentiation and growth control; however, in tumors it is frequently overexpressed and redistributes to the cytoplasm and plasma membrane, where it functions to propagate signals from growth factor receptors (e.g. EGFR, HER2, Met) and other upstream stimuli. Such signaling events promote cell proliferation, migration, invasion, and survival, thereby contributing to tumor progression and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PTK6 exerts its function by phosphorylating a diverse array of substrates such as paxillin, Sam68, p190RhoGAP, STAT3, and IRS-4, among others. Through these substrates it modulates critical downstream pathways—including Ras/MAPK, AKT, β-catenin/TCF, and focal adhesion kinase (FAK) cascades—thereby controlling cytoskeletal dynamics, cell cycle progression, and survival signaling. In addition, the kinase activity of PTK6 (often marked by phosphorylation of its activation loop tyrosine residue [Y342]) and its regulation by intramolecular interactions involving the SH3 and SH2 domains are essential for substrate recognition and subsequent signaling output. Its activity is further modulated by several regulatory proteins and phosphatases (for example, PTEN, Hsp90/CHIP, and SOCS3) which can either attenuate or potentiate its signaling functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe oncogenic potential of PTK6 is tightly linked to its subcellular localization and the contexts in which it is activated. When targeted to the plasma membrane, PTK6 drives epithelial-to-mesenchymal transition (EMT), enhances cell motility, and promotes anchorage-independent growth and metastasis via activation of effectors such as FAK, ERK, AKT, and STAT family members. In contrast, nuclear PTK6 appears to exert growth‐inhibitory functions by attenuating β‑catenin/TCF transcription. Moreover, PTK6 facilitates stress response signaling, collaborates with adaptor proteins like STAP-2, IRS-4, and Dok1, and modulates cell cycle regulators (e.g. via p27 phosphorylation facilitating cdk4 activation), thereby contributing to tumor progression and drug resistance across diverse cancer types. These multifaceted roles not only underscore its potential as a prognostic marker but also highlight PTK6 as an attractive target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hsin-Yi Chen, Che-Hung Shen, Yuh-Tyng Tsai, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Altered localization and activity of the intracellular tyrosine kinase BRK/Sik in prostate tumor cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1206465"}], "href": "https://doi.org/10.1038/sj.onc.1206465"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12833144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12833144"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Michael S Serfas, Angela L Tyner "}, {"type": "b", "children": [{"type": "t", "text": "Brk, Srm, Frk, and Src42A form a distinct family of intracellular Src-like tyrosine kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/096504003108748438"}], "href": "https://doi.org/10.3727/096504003108748438"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12725532"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12725532"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "John H Coyle, Brian W Guzik, Yeou-Cherng Bor, et al. 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Synonyms	BRK
Proteins	PTK6_HUMAN
NCBI Gene ID	5753
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PTK6 has 6,017 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 110 datasets.

Click the + buttons to view associations for PTK6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PTK6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PTK6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PTK6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PTK6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PTK6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PTK6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PTK6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTK6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PTK6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PTK6 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PTK6 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PTK6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PTK6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PTK6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PTK6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PTK6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PTK6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PTK6 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PTK6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PTK6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PTK6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PTK6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PTK6 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PTK6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PTK6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PTK6 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PTK6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PTK6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PTK6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PTK6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PTK6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PTK6 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PTK6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PTK6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PTK6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PTK6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PTK6 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PTK6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PTK6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PTK6 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of PTK6 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.