Tchem EPHB2 Ephrin type-B receptor 2

Protein Summary

Description

Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. This gene encodes a member of the Eph receptor family of receptor tyrosine kinase transmembrane glycoproteins. These receptors are composed of an N-terminal glycosylated ligand-binding domain, a transmembrane region and an intracellular kinase domain. They bind ligands called ephrins and are involved in diverse cellular processes including motility, division, and differentiation. A distinguishing characteristic of Eph-ephrin signaling is that both receptors and ligands are competent to transduce a signaling cascade, resulting in bidirectional signaling. This protein belongs to a subgroup of the Eph receptors called EphB. Proteins of this subgroup are distinguished from other members of the family by sequence homology and preferential binding affinity for membrane-bound ephrin-B ligands. Allelic variants are associated with prostate and brain cancer susceptibility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

Uniprot Accession IDs

• P29323
• O43477
• Q5T0U6
• Q5T0U7
• Q5T0U8

Gene Name

• EPHB2

Ensembl ID

• ENST00000374630
• ENSP00000363761
• ENSG00000133216
• ENST00000374632
• ENSP00000363763
• ENST00000400191
• ENSP00000383053

Symbol

• DRT
• EPHT3
• EPTH3
• ERK
• HEK5
• TYRO5
• DRT
• EK5
• ERK
• CAPB
• Hek5
• PCBC
• EPHT3
• Tyro5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
co-expressed gene	1
protein domain	1
molecular function	0.99
transcription factor perturbation	0.88
biological process	0.86

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Eph Family / Ephrin Type-b Receptor 2

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: 513.12   (req: < 5)

Gene RIFs: 74   (req: <= 3)

Antibodies: 611   (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: 513.12   (req: >= 5)

Gene RIFs: 74   (req: > 3)

Antibodies: 611   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 52

Tchem

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

Active Ligands: 11

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

EPHB2Tchem Kinase

INHIBITOR pKd : 8.38

dasatinib

EPHB2Tchem Kinase

INHIBITOR pKd : 7.89

tivozanib

EPHB2Tchem Kinase

INHIBITOR pIC50 : 9.62

Active Ligands (11)

Explore Active Ligands

1 – 10 of 11

foretinib

EPHB2Tchem Kinase

pKd : 7.92

PD-173955

EPHB2Tchem Kinase

pKd : 7.92

CHEMBL4568087

EPHB2Tchem Kinase

pIC50 : 8.89

TG-100572

EPHB2Tchem Kinase

pKd : 9.05

CHEMBL249097

EPHB2Tchem Kinase

pKd : 8.3

CHEMBL566515

EPHB2Tchem Kinase

pIC50 : 9.04

DDR1/2 inhibitor 5n

EPHB2Tchem Kinase

pKd : 7.96

compound 20 [PMID: 23489211]

EPHB2Tchem Kinase

pIC50 : 5.82

CHEMBL3426225

EPHB2Tchem Kinase

pIC50 : 9.1

CHEMBL3426917

EPHB2Tchem Kinase

pIC50 : 8.62

Protein-Protein Interactions (245)

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1 – 10 of 245

• See Interactions on String-DB

SPSB2

Tbio

Novelty:  0.07223184

p_int:  0.999999981

p_ni:  1.7e-8

p_wrong:  2e-9

Score:  0.557

Data Source:  BioPlex,STRINGDB

EFNB2

Tbio

Novelty:  0.00255095

p_int:  0.999999861

p_ni:  5.9e-8

p_wrong:  8e-8

Score:  0.999

Data Source:  BioPlex,STRINGDB

MYCBP2

Tbio

Family:  Enzyme

Novelty:  0.00413684

p_int:  0.999796533

p_ni:  0.000203468

Data Source:  BioPlex

FBXO45

Tbio

Novelty:  0.05784607

p_int:  0.999685567

p_ni:  0.000305167

p_wrong:  0.000009266

Data Source:  BioPlex

HSPA5

Tchem

Novelty:  0.00043424

p_int:  0.90002893

p_ni:  0.09997107

Score:  0.157

Data Source:  BioPlex,STRINGDB

EFNA5

Tbio

Novelty:  0.00134985

Score:  0.999

Data Source:  STRINGDB

EFNB1

Tbio

Novelty:  0.00523161

Score:  0.997

Data Source:  STRINGDB

EFNA1

Tbio

Family:  Kinase

Novelty:  0.00732252

Score:  0.993

Data Source:  STRINGDB

EFNA3

Tbio

Novelty:  0.01819539

Score:  0.993

Data Source:  STRINGDB

EFNA2

Tbio

Novelty:  0.01184859

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 (208)

Reactome (6)

KEGG (1)

PathwayCommons (7)

WikiPathways (194)

Axon guidance (R-HSA-422475)

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Find Similar Targets

Items per page:

5

1 – 5 of 6

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
Reactome	Ephrin signaling	19 targets	R-HSA-3928664

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
Ephrin signaling	19 targets	R-HSA-3928664

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (67)

Functions (10)

Components (15)

Processes (42)

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Items per page:

10

1 – 10 of 10

GO Term	Evidence	Assigned by
protein tyrosine kinase activity	Inferred from Experiment (EXP)	Reactome
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
amyloid-beta binding	Inferred from Sequence or structural Similarity (ISS)	ARUK-UCL
protein-containing complex binding	Inferred from Sequence or structural Similarity (ISS)	ARUK-UCL
transmembrane-ephrin receptor activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
axon guidance receptor activity	Inferred from Electronic Annotation (IEA)	Ensembl
identical protein binding	Inferred from Electronic Annotation (IEA)	Ensembl
signaling receptor binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (7)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	1	1	1		31.4
triiodothyronine measurement	EFO_0008392	2	1	2		26.1
thyroxine measurement	EFO_0005130	1	1	1		24.5
body mass index	EFO_0004340	1	1	1		21.4
waist-hip ratio	EFO_0004343	1	1	1		10.3

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean corpuscular volume	EFO_0004526	1		31.4
triiodothyronine measurement	EFO_0008392	2		26.1
thyroxine measurement	EFO_0005130	1		24.5
body mass index	EFO_0004340	1		21.4
waist-hip ratio	EFO_0004343	1		10.3

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Cell membrane
Cell projection
Complete proteome
Developmental protein
Disease mutation
Disulfide bond
Glycoprotein

GWAS Trait Find Similar Targets

No Header	No Header
BMI-adjusted hip circumference
body height
body mass index
mean corpuscular volume
thyroxine measurement
triiodothyronine measurement
waist-hip ratio

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
hearing/vestibular/ear phenotype
nervous system phenotype
renal/urinary system phenotype
reproductive system phenotype
vision/eye phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	EPH receptor B2	VGNC:10612	456613
Mouse	Eph receptor B2	MGI:99611	13844
Rat	Eph receptor B2	RGD:1564232	313633
Dog	EPH receptor B2	VGNC:40411	487380
Cow	EPH receptor B2	VGNC:54424	535137

Species	Name	OMA	EggNOG	Inparanoid
Chimp	EPH receptor B2
Mouse	Eph receptor B2
Rat	Eph receptor B2
Dog	EPH receptor B2
Cow	EPH receptor B2

Publication Statistics

PubMed Score 513.12

PubMed score by year

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PubTator Score 379.27

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Patents

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Related Publications

Text Mined References (139)

GeneRif Annotations (74)

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PMID	Year	Title