Tclin TNK2 Activated CDC42 kinase 1

Protein Summary

Description

Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). This gene encodes a tyrosine kinase that binds Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q07912
• Q6ZMQ0
• Q8N6U7
• Q96H59
• ACK-1

Gene Name

• TNK2

Ensembl ID

• ENST00000333602
• ENSP00000329425
• ENSG00000061938
• ENST00000381916
• ENSP00000371341
• ENST00000439230
• ENSP00000395588

Symbol

• ACK1
• ACK
• ACK1
• ACK-1
• p21cdc42Hs

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	1
transcription factor perturbation	0.88
hub protein	0.85
interacting protein	0.84

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: 127.31   (req: < 5)

Gene RIFs: 55   (req: <= 3)

Antibodies: 713   (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: 127.31   (req: >= 5)

Gene RIFs: 55   (req: > 3)

Antibodies: 713   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

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

Active Ligands: 116

Tclin

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

Active Drugs: 3

Protein Sequence and Structure

Residue Counts

Protein Sequence

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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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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (3)

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1 – 3 of 3

bosutinib

TNK2Tclin Kinase

pKd : 7.54

dasatinib

TNK2Tclin Kinase

pKd : 7.57

lorlatinib

TNK2Tclin Kinase

INHIBITOR pIC50 : 7.77

Active Ligands (116)

Explore Active Ligands

1 – 10 of 116

staurosporine

TNK2Tclin Kinase

pKd : 7.77

lestaurtinib

TNK2Tclin Kinase

pKd : 8.18

SID103905531

TNK2Tclin Kinase

pKi : 8.8

TAE-684

TNK2Tclin Kinase

pKd : 8.7

SID103904591

TNK2Tclin Kinase

pKi : 8.4

PD-173955

TNK2Tclin Kinase

pKd : 7.57

SID103904402

TNK2Tclin Kinase

pKi : 7.6

ilorasertib

TNK2Tclin Kinase

pKi : 8.1

PD166285

TNK2Tclin Kinase

pKi : 8.9

SID103904323

TNK2Tclin Kinase

pKi : 7.8

Protein-Protein Interactions (98)

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1 – 10 of 98

• See Interactions on String-DB

NCK1

Tbio

Novelty:  0.00352084

p_int:  0.999999964

p_ni:  3.4e-8

p_wrong:  1e-9

Score:  0.658

Data Source:  BioPlex,STRINGDB

NCK2

Tbio

Novelty:  0.02220251

p_int:  0.999999663

p_ni:  1.17e-7

p_wrong:  2.21e-7

Score:  0.428

Data Source:  BioPlex,STRINGDB

HSP90AB3P

Tdark

p_int:  0.999989975

p_ni:  0.000010024

p_wrong:  1e-9

Data Source:  BioPlex

ISG15

Tbio

Novelty:  0.00203781

p_int:  0.999975164

p_ni:  0.00000885

p_wrong:  0.000015986

Score:  0.274

Data Source:  BioPlex,STRINGDB

GRB2

Tchem

Novelty:  0.00091605

p_int:  0.983686966

p_ni:  7.95e-7

p_wrong:  0.016312239

Score:  0.924

Data Source:  BioPlex,STRINGDB

CDC37

Tbio

Novelty:  0.03730196

p_int:  0.786919817

p_ni:  0.213080183

Score:  0.358

Data Source:  BioPlex,STRINGDB

CDC42

Tchem

Family:  Enzyme

Novelty:  0.00032619

Score:  0.998

Data Source:  STRINGDB

BCAR1

Tbio

Novelty:  0.00329214

Score:  0.973

Data Source:  STRINGDB

AR

Tclin

Family:  NR

Novelty:  0.00013531

Score:  0.858

Data Source:  STRINGDB

WWOX

Tbio

Family:  Enzyme

Novelty:  0.00335243

Score:  0.849

Data Source:  STRINGDB

Pathways (6)

PathwayCommons (2)

WikiPathways (4)

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5

1 – 2 of 2

Data Source	Name	Explore in Pharos	Explore in Source
PathwayCommons: netpath	EGFR1	472 targets	PathwayCommons: netpath
PathwayCommons: pid	CDC42 signaling events	71 targets	PathwayCommons: pid

Name	Explore in Pharos	Explore in Source
EGFR1	472 targets	PathwayCommons: netpath
CDC42 signaling events	71 targets	PathwayCommons: pid

Gene Ontology Terms (32)

Functions (11)

Components (12)

Processes (9)

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10

1 – 10 of 11

GO Term	Evidence	Assigned by
epidermal growth factor receptor binding	Inferred from Direct Assay (IDA)	BHF-UCL
protein serine/threonine/tyrosine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
protein tyrosine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
non-membrane spanning protein tyrosine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
WW domain binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
GTPase inhibitor activity	Traceable Author Statement (TAS)	ProtInc
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

GWAS Traits (2)

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5

1 – 2 of 2

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
creatinine measurement	EFO_0004518	1	1	1		48.5
glomerular filtration rate	EFO_0005208	1	1	1		42.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 2 of 2

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
creatinine measurement	EFO_0004518	1		48.5
glomerular filtration rate	EFO_0005208	1		42.3

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Cell junction
Cell membrane
Coated pit
Complete proteome
Cytoplasm
Cytoplasmic vesicle
Endocytosis

GWAS Trait Find Similar Targets

No Header	No Header
creatinine measurement
glomerular filtration rate

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	tyrosine kinase non receptor 2		711655
Mouse	tyrosine kinase, non-receptor, 2	MGI:1858308	51789
Rat	tyrosine kinase, non-receptor, 2	RGD:1305957	303882
Dog	tyrosine kinase non receptor 2	VGNC:47680	488025
Horse	tyrosine kinase non receptor 2 [Source:HGNC Symbol;Acc:HGNC:19297]

Species	Name	OMA	EggNOG	Inparanoid
Macaque	tyrosine kinase non receptor 2
Mouse	tyrosine kinase, non-receptor, 2
Rat	tyrosine kinase, non-receptor, 2
Dog	tyrosine kinase non receptor 2
Horse	tyrosine kinase non receptor 2 [Source:HGNC Symbol;Acc:HGNC:19297]

Publication Statistics

PubMed Score 127.31

PubMed score by year

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PubTator Score 109.34

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