Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PTK6 (Q13882) - Overview - Molecular Target Synopsis

Protein


PTK6, Protein-tyrosine kinase 6
Enzyme Classification 2.7.10.2
UniProt Q13882

Also Known as PTK6_HUMAN, PTK6, BRK

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., Isoform 2 inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins. Interacts with GAP-A.p65 (By similarity). Interacts (via SH3 and SH2 domains) with KHDRBS1. Interacts (via SH3 and SH2 domains) with phosphorylated IRS4. Interacts with ADAM15. Interacts (via SH3 domain) with SFPQ. Interacts with EGFR and ERBB2. Interacts with STAP2. Interacts with PNX. Interacts with SFPQ. Interacts with PTK/ATK. Interacts with CTNNB1.

6CZ2
STRUCTURE OF THE PTK6 KINASE DOMAIN
RCSB/PDB
Inspect Structure
See all 3D Structures for PTK6

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
451ENSG00000101213ENST00000217185ENSP00000217185Q13882-1
350ENSG00000101213ENST00000542869ENSP00000442460
134Q13882-2

Drugs


PTK6 is targeted by Approved Drug Vandetanib. (see details)
Vandetanib

Sub-cellular localization


UniProt: PTK6 is active in the following subcellular-locations: cell projection, cytoplasm, membrane, nucleus, ruffle.
GO terms: PTK6 is active in the following subcellular-locations: cytoplasm, cytosol, extrinsic component of cytoplasmic side of plasma membrane, nuclear body, nucleoplasm, nucleus, plasma membrane, ruffle.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PTK6 has gain in 7 cell-lines, loss in 1 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: COLO205, HCC_2998, T47D

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SNU-C1, BxPC-3, PK-59

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHEK, HeLa-S3, MCF-7

(see details)

RNA Interference


PTK6 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: PCI30, SKGT4. (see details)

3D Structures


For PTK6 there are:
8 structures (14 chains) solved
5 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

PTK6 is solved in complex with the approved drug(s):

1N1/DASATINIB (5H2U_A, 5H2U_B, 5H2U_C, 5H2U_D).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PTK6 has been screened with 932 compounds (1669 bioactivities), 111 compounds have bioactivities that show binding affinity of <= 500nM (155 bioactivities). (see details)