Tchem EPHA3 Ephrin type-A receptor 3

Protein Summary

Description

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P29320
• Q9H2V3
• Q9H2V4

Gene Name

• EPHA3

Ensembl ID

• ENST00000336596
• ENSP00000337451
• ENSG00000044524
• ENST00000452448
• ENSP00000399926

Symbol

• ETK
• ETK1
• HEK
• TYRO4
• EK4
• ETK
• HEK
• ETK1
• HEK4
• TYRO4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.99
transcription factor perturbation	0.94
microRNA	0.93
gene perturbation	0.8

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Eph Family / Ephrin Type-a Receptor 3

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: 228.46   (req: < 5)

Gene RIFs: 36   (req: <= 3)

Antibodies: 457   (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: 228.46   (req: >= 5)

Gene RIFs: 36   (req: > 3)

Antibodies: 457   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 24

Tchem

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

Active Ligands: 12

Tclin

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

Active Drugs: 2

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

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 (2)

Explore Approved Drugs

1 – 2 of 2

bosutinib

EPHA3Tchem Kinase

INHIBITOR pKd : 8.38

dasatinib

EPHA3Tchem Kinase

INHIBITOR pKd : 7.89

Active Ligands (12)

Explore Active Ligands

1 – 10 of 12

staurosporine

EPHA3Tchem Kinase

pKd : 7.89

foretinib

EPHA3Tchem Kinase

pKd : 7.92

PD-173955

EPHA3Tchem Kinase

pKd : 7.92

CHEMBL4568087

EPHA3Tchem Kinase

pIC50 : 8.89

CHEMBL249097

EPHA3Tchem Kinase

pKd : 8.3

CHEMBL1784637

EPHA3Tchem Kinase

pIC50 : 9.7

CHEMBL566515

EPHA3Tchem Kinase

pIC50 : 9.04

CHEMBL459850

EPHA3Tchem Kinase

pIC50 : 9

sitravatinib

EPHA3Tchem Kinase

pIC50 : 9.3

compound 20 [PMID: 23489211]

EPHA3Tchem Kinase

pIC50 : 5.82

Protein-Protein Interactions (134)

Explore Interacting Targets

1 – 10 of 134

• See Interactions on String-DB

EPHA7

Tchem

Family:  Kinase

Novelty:  0.01065563

p_int:  0.999935474

p_ni:  0.000064479

p_wrong:  4.7e-8

Score:  0.933

Data Source:  BioPlex,STRINGDB

EFNA5

Tbio

Novelty:  0.00134985

p_int:  0.999878385

p_ni:  0.000121615

Score:  0.999

Data Source:  BioPlex,STRINGDB

LRRIQ1

Tdark

Novelty:  1.8251367

p_int:  0.99128511

p_ni:  0.008713257

p_wrong:  0.000001632

Score:  0.554

Data Source:  BioPlex,STRINGDB

FAM118B

Tdark

Novelty:  0.48168976

p_int:  0.95513242

p_ni:  0.033751333

p_wrong:  0.011116247

Score:  0.165

Data Source:  BioPlex,STRINGDB

SLAMF1

Tbio

Novelty:  0.00112892

p_int:  0.946129735

p_ni:  0.041240495

p_wrong:  0.01262977

Score:  0.157

Data Source:  BioPlex,STRINGDB

HLA-DRA

Tbio

Novelty:  0.0060214

p_int:  0.881035982

p_ni:  0.091317198

p_wrong:  0.027646819

Score:  0.181

Data Source:  BioPlex,STRINGDB

TMEM231

Tbio

Novelty:  0.17100188

p_int:  0.781509957

p_ni:  0.193004433

p_wrong:  0.025485609

Score:  0.179

Data Source:  BioPlex,STRINGDB

CEACAM21

Tdark

Novelty:  0.46116153

p_int:  0.770190719

p_ni:  0.20593599

p_wrong:  0.02387329

Data Source:  BioPlex

EFNB2

Tbio

Novelty:  0.00255095

Score:  0.998

Data Source:  STRINGDB

EFNB1

Tbio

Novelty:  0.00523161

Score:  0.995

Data Source:  STRINGDB

Nearest Tclin Targets (1)

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Downstream (1)

1 – 1 of 1

ABL1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  1

1: Axon guidance

Pathways (11)

Reactome (4)

KEGG (1)

PathwayCommons (4)

WikiPathways (2)

Axon guidance (R-HSA-422475)

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Find Similar Targets

Items per page:

5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Axon guidance	533 targets	R-HSA-422475
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	EPH-Ephrin signaling	92 targets	R-HSA-2682334
Reactome	EPH-ephrin mediated repulsion of cells	49 targets	R-HSA-3928665

Name	Explore in Pharos	Explore in Source
Axon guidance	533 targets	R-HSA-422475
Developmental Biology	1055 targets	R-HSA-1266738
EPH-Ephrin signaling	92 targets	R-HSA-2682334
EPH-ephrin mediated repulsion of cells	49 targets	R-HSA-3928665

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (31)

Functions (5)

Components (7)

Processes (19)

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Items per page:

10

1 – 5 of 5

GO Term	Evidence	Assigned by
GPI-linked ephrin receptor activity	Inferred from Direct Assay (IDA)	UniProtKB
transmembrane receptor protein tyrosine kinase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transmembrane signaling receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
transmembrane-ephrin receptor activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (11)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 11

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
atrial fibrillation	EFO_0000275	2	2	0	1.1	53.7
mathematical ability	EFO_0004875	2	2	2		51.4
intelligence	EFO_0004337	2	3	0	5.6	44
smoking behaviour measurement	EFO_0005671	1	1	1		35
tea consumption measurement	EFO_0010091	2	1	2		35

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 11

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
atrial fibrillation	EFO_0000275	0	1.1	53.7
mathematical ability	EFO_0004875	2		51.4
intelligence	EFO_0004337	0	5.6	44
smoking behaviour measurement	EFO_0005671	1		35
tea consumption measurement	EFO_0010091	2		35

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Cell adhesion
Cell membrane
Complete proteome
Direct protein sequencing
Glycoprotein
Kinase
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
atrial fibrillation
BMI-adjusted waist-hip ratio
body mass index
C-reactive protein measurement
cleft lip
intelligence
mathematical ability
smoking behavior
smoking behaviour measurement
tea consumption measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
respiratory system phenotype

IDG Resources

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	EPH receptor A3	VGNC:1809	460531
Macaque	EPH receptor A3		694583
Mouse	Eph receptor A3	MGI:99612	13837
Rat	Eph receptor A3	RGD:68389	29210
Dog	EPH receptor A3	VGNC:40406	487930

Species	Name	OMA	EggNOG	Inparanoid
Chimp	EPH receptor A3
Macaque	EPH receptor A3
Mouse	Eph receptor A3
Rat	Eph receptor A3
Dog	EPH receptor A3

Publication Statistics

PubMed Score 228.46

PubMed score by year

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PubTator Score 103.27

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Patents

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Related Publications

Text Mined References (66)

GeneRif Annotations (36)

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PMID	Year	Title