Tchem EPHA5 Ephrin type-A receptor 5

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Eph Family / 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

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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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: 88.64   (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: 88.64   (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: 5

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

bosutinib

EPHA5Tchem Kinase

Kd : 7.57

dasatinib

EPHA5Tchem Kinase

Kd : 9.62

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

CHEMBL1230609

EPHA5Tchem Kinase

Kd : 8.18

CHEMBL386051

EPHA5Tchem Kinase

Kd : 7.85

CHEMBL249097

EPHA5Tchem Kinase

Kd : 8.52

CHEMBL566515

EPHA5Tchem Kinase

IC50 : 8.52000046

compound 20 [PMID: 23489211]

EPHA5Tchem Kinase

IC50 : 5.61999989

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		95.5
self reported educational attainment	EFO_0004784	2	3	3		89.1
cognitive function measurement	EFO_0008354	1	1	1		82
intelligence	EFO_0004337	1	1	1		25.4
schizophrenia	EFO_0000692	1	1	1		25.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 6

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4		95.5
self reported educational attainment	EFO_0004784	3		89.1
cognitive function measurement	EFO_0008354	1		82
intelligence	EFO_0004337	1		25.4
schizophrenia	EFO_0000692	1		25.4

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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

Protein Structure (2 Structures, 1 AlphaFold Model)

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-P54756-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2

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 (8)

Reactome (4)

KEGG (1)

PathwayCommons (3)

Axon guidance (R-HSA-422475)

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Find Similar Targets

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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

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

Protein-Protein Interactions (120)

Explore Interacting Targets

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

Publication Statistics

PubMed Score  88.64

PubMed score by year

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PubTator Score  33.29

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

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

GWAS Trait Find Similar Targets

cognitive function measurement
intelligence
mathematical ability
risk-taking behaviour
schizophrenia
self reported educational attainment

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
nervous system phenotype