Tchem EPHA5 Ephrin type-A receptor 5

Protein Summary

Description

Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion (By similarity). 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. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

Uniprot Accession IDs

• P54756
• Q7Z3F2

Gene Name

• EPHA5

Ensembl ID

• ENST00000273854
• ENSP00000273854
• ENSG00000145242
• ENST00000354839
• ENSP00000346899

Symbol

• BSK
• EHK1
• HEK7
• TYRO4
• EK7
• CEK7
• EHK1
• HEK7
• EHK-1
• TYRO4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.99
kinase perturbation	0.81
microRNA	0.77
virus perturbation	0.72

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Eph Family / Ephrin Type-a Receptor 5

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: 92.71   (req: < 5)

Gene RIFs: 15   (req: <= 3)

Antibodies: 487   (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: 92.71   (req: >= 5)

Gene RIFs: 15   (req: > 3)

Antibodies: 487   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 19

Tchem

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

Active Ligands: 7

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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Expression Data (0 Tissues)

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No expression data found

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

EPHA5Tchem Kinase

INHIBITOR pKd : 8.38

dasatinib

EPHA5Tchem Kinase

INHIBITOR pKd : 7.89

ponatinib

EPHA5Tchem Kinase

INHIBITOR pKi : 8.8

Active Ligands (7)

Explore Active Ligands

1 – 7 of 7

staurosporine

EPHA5Tchem Kinase

pKd : 7.89

foretinib

EPHA5Tchem Kinase

pKd : 7.92

PD-173955

EPHA5Tchem Kinase

pKd : 7.92

TG-100572

EPHA5Tchem Kinase

pKd : 9.05

CHEMBL249097

EPHA5Tchem Kinase

pKd : 8.3

CHEMBL566515

EPHA5Tchem Kinase

pIC50 : 9.04

compound 20 [PMID: 23489211]

EPHA5Tchem Kinase

pIC50 : 5.82

Protein-Protein Interactions (120)

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1 – 10 of 120

• See Interactions on String-DB

EFNA5

Tbio

Novelty:  0.00134985

p_int:  0.999997399

p_ni:  3.11e-7

p_wrong:  0.00000229

Score:  0.998

Data Source:  BioPlex,STRINGDB

CST9L

Tdark

Novelty:  0.21941207

p_int:  0.999606149

p_ni:  0.000004429

p_wrong:  0.000389423

Data Source:  BioPlex

TSPAN3

Tbio

Novelty:  0.06362133

p_int:  0.99769917

p_ni:  3.56e-7

p_wrong:  0.002300474

Score:  0.77

Data Source:  BioPlex,STRINGDB

EFNB2

Tbio

Novelty:  0.00255095

p_int:  0.996609814

p_ni:  3.14e-7

p_wrong:  0.003389872

Score:  0.999

Data Source:  BioPlex,STRINGDB

EFNA1

Tbio

Family:  Kinase

Novelty:  0.00732252

Score:  0.995

Data Source:  STRINGDB

EFNA3

Tbio

Novelty:  0.01819539

Score:  0.995

Data Source:  STRINGDB

EFNA2

Tbio

Novelty:  0.01184859

Score:  0.995

Data Source:  STRINGDB

EFNA4

Tbio

Novelty:  0.03628159

Score:  0.995

Data Source:  STRINGDB

EFNB1

Tbio

Novelty:  0.00523161

Score:  0.993

Data Source:  STRINGDB

EFNB3

Tbio

Novelty:  0.0120367

Score:  0.993

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 (8)

Reactome (4)

KEGG (1)

PathwayCommons (3)

Axon guidance (R-HSA-422475)

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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 (30)

Functions (6)

Components (11)

Processes (13)

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Items per page:

10

1 – 6 of 6

GO Term	Evidence	Assigned by
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
ephrin receptor activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
GPI-linked ephrin receptor activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (6)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4	2	4		77.8
self reported educational attainment	EFO_0004784	2	3	3		72
cognitive function measurement	EFO_0008354	1	1	1		56.8
risk-taking behaviour	EFO_0008579	1	1	1		42.3
schizophrenia	EFO_0000692	1	1	1		33.1

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4		77.8
self reported educational attainment	EFO_0004784	3		72
cognitive function measurement	EFO_0008354	1		56.8
risk-taking behaviour	EFO_0008579	1		42.3
schizophrenia	EFO_0000692	1		33.1

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UniProt Keyword Find Similar Targets

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3D-structure
Alternative splicing
ATP-binding
Cell membrane
Cell projection
Complete proteome
Glycoprotein
Kinase
Membrane
Neurogenesis

GWAS Trait Find Similar Targets

No Header	No Header
cognitive function measurement
intelligence
mathematical ability
risk-taking behaviour
schizophrenia
self reported educational attainment

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	EPH receptor A5	VGNC:2035	461299
Macaque	EPH receptor A5		712074
Mouse	Eph receptor A5	MGI:99654	13839
Rat	EPH receptor A5	RGD:620831	79208
Dog	EPH receptor A5	VGNC:40408	100684553

Species	Name	OMA	EggNOG	Inparanoid
Chimp	EPH receptor A5
Macaque	EPH receptor A5
Mouse	Eph receptor A5
Rat	EPH receptor A5
Dog	EPH receptor A5

Publication Statistics

PubMed Score 92.71

PubMed score by year

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PubTator Score 33.29

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Patents

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Related Publications

Text Mined References (41)

GeneRif Annotations (15)

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PMID	Year	Title