Tchem PTK6 Protein-tyrosine kinase 6

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Src Family / Protein-tyrosine Kinase 6

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• Q13882
• B2RCR3
• B4DW46
• Q58F01

Gene Name

• PTK6

Ensembl ID

• ENST00000217185
• ENSP00000217185
• ENSG00000101213
• ENST00000542869
• ENSP00000442460

Symbol

• BRK
• BRK

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.97
molecular function	0.95
biological process	0.89
biological term	0.57
gene perturbation	0.56

Related Tools

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 240.82   (req: < 5)

Gene RIFs: 73   (req: <= 3)

Antibodies: 478   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 240.82   (req: >= 5)

Gene RIFs: 73   (req: > 3)

Antibodies: 478   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 22

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 60

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2

Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

dasatinib

PTK6Tchem Kinase

Kd : 8.11

ibrutinib

PTK6Tchem Kinase

IC50 : 8.48

Active Ligands (60)

Explore Active Ligands

1 – 10 of 60

TAE-684

PTK6Tchem Kinase

Ki : 7.9

foretinib

PTK6Tchem Kinase

Kd : 8.37

SID103904418

PTK6Tchem Kinase

Ki : 7.9

CHEMBL249097

PTK6Tchem Kinase

Kd : 8.7

CHEMBL3647967

PTK6Tchem Kinase

IC50 : 8.48

SID103904991

PTK6Tchem Kinase

Ki : 8.5

PP1

PTK6Tchem Kinase

Ki : 8.1

tirabrutinib

PTK6Tchem Kinase

Kd : 7.6

SID103904796

PTK6Tchem Kinase

Ki : 7.8

SID103904891

PTK6Tchem Kinase

Ki : 7.8

GWAS Traits (12)

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5

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glomerular filtration rate	EFO_0005208	2	2	2		70.5
electrocardiography	EFO_0004327	1	2	32		61.8
hair shape measurement	EFO_0007824	1	1	1		61
daytime rest measurement	EFO_0007828	1	1	1		55.2
reticulocyte count	EFO_0007986	1	1	1		31.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glomerular filtration rate	EFO_0005208	2		70.5
electrocardiography	EFO_0004327	32		61.8
hair shape measurement	EFO_0007824	1		61
daytime rest measurement	EFO_0007828	1		55.2
reticulocyte count	EFO_0007986	1		31.4

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Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	PTK6 protein tyrosine kinase 6	MGI:99683	20459
Rat	protein tyrosine kinase 6	RGD:1309098	366275
Horse	protein tyrosine kinase 6	VGNC:22004	100060532
Cow	protein tyrosine kinase 6	VGNC:33520	529814
Opossum	protein tyrosine kinase 6		100025045

Species	Name	OMA	EggNOG	Inparanoid
Mouse	PTK6 protein tyrosine kinase 6
Rat	protein tyrosine kinase 6
Horse	protein tyrosine kinase 6
Cow	protein tyrosine kinase 6
Opossum	protein tyrosine kinase 6

Protein Structure (8 Structures, 1 AlphaFold Model)

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Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q13882-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 8

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (27)

Reactome (24)

PathwayCommons (1)

WikiPathways (2)

Cell Cycle (R-HSA-1640170)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle, Mitotic	495 targets	R-HSA-69278
Reactome	Cyclin A:Cdk2-associated events at S phase entry	86 targets	R-HSA-69656
Reactome	Cyclin D associated events in G1	45 targets	R-HSA-69231
Reactome	Cyclin E associated events during G1/S transition	84 targets	R-HSA-69202

Name	Explore in Pharos	Explore in Source
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle, Mitotic	495 targets	R-HSA-69278
Cyclin A:Cdk2-associated events at S phase entry	86 targets	R-HSA-69656
Cyclin D associated events in G1	45 targets	R-HSA-69231
Cyclin E associated events during G1/S transition	84 targets	R-HSA-69202

Gene Ontology Terms (30)

Functions (5)

Components (8)

Processes (17)

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10

1 – 5 of 5

GO Term	Evidence	Assigned by
protein tyrosine kinase activity	Inferred from Experiment (EXP)	Reactome
non-membrane spanning protein tyrosine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
signaling receptor binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (83)

Explore Interacting Targets

1 – 10 of 83

• See Interactions on String-DB

KHDRBS1

Tbio

Novelty:  0.00647929

Score:  0.988

Data Source:  Reactome,STRINGDB

STAP2

Tbio

Novelty:  0.00375696

Score:  0.984

Data Source:  Reactome,STRINGDB

PXN

Tbio

Novelty:  0.00082031

Score:  0.971

Data Source:  Reactome,STRINGDB

STAT3

Tchem

Family:  TF

Novelty:  0.00011808

Score:  0.968

Data Source:  Reactome,STRINGDB

ARHGAP35

Tbio

Family:  Enzyme

Novelty:  0.00970784

Score:  0.967

Data Source:  Reactome,STRINGDB

BCAR1

Tbio

Novelty:  0.00329214

Score:  0.964

Data Source:  Reactome,STRINGDB

KHDRBS3

Tbio

Novelty:  0.00490069

Score:  0.964

Data Source:  Reactome,STRINGDB

EGFR

Tclin

Family:  Kinase

Novelty:  0.00007274

Score:  0.953

Data Source:  Reactome,STRINGDB

KHDRBS2

Tbio

Novelty:  0.01986638

Score:  0.953

Data Source:  Reactome,STRINGDB

ERBB2

Tclin

Family:  Kinase

Novelty:  0.00003761

Score:  0.952

Data Source:  Reactome,STRINGDB

Publication Statistics

PubMed Score  240.82

PubMed score by year

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PubTator Score  94.84

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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Ortholog Sequence Conservation

WebLogo Color Code

PolarG S T Y C

NeutralQ N

BasicK R H

AcidicD E

HydrophobicA V L I P W F M

Compare across kinases on ProKinO

Structural Annotations

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UniProt Keyword Find Similar Targets

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3D-structure
Alternative splicing
ATP-binding
Cell projection
Complete proteome
Cytoplasm
Kinase
Membrane
Nucleotide-binding
Nucleus

GWAS Trait Find Similar Targets

No Header	No Header
autism spectrum disorder
basophil count
creatinine measurement
daytime rest measurement
electrocardiography
glomerular filtration rate
hair shape measurement
mean reticulocyte volume
reticulocyte count
reticulocyte measurement

MGI Phenotype Find Similar Targets

No Header	No Header
digestive/alimentary phenotype
renal/urinary system phenotype