Tchem EPHB3 Ephrin type-B receptor 3

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. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. In addition to its role in axon guidance plays also an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt. Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. This gene encodes a receptor for ephrin-B family members. [provided by RefSeq, Mar 2010]

Uniprot Accession IDs

• P54753
• Q7Z740

Gene Name

• EPHB3

Ensembl ID

• ENST00000330394
• ENSP00000332118
• ENSG00000182580

Symbol

• ETK2
• HEK2
• TYRO6
• EK2
• ETK2
• HEK2
• TYRO6

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.98
PubMedID	0.82
biological process	0.78
transcription factor binding site profile	0.72

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: 100.94   (req: < 5)

Gene RIFs: 18   (req: <= 3)

Antibodies: 510   (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: 100.94   (req: >= 5)

Gene RIFs: 18   (req: > 3)

Antibodies: 510   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 31

Tchem

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

Active Ligands: 2

Tclin

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

Active Drug: 1

Approved Drugs (1)

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1 – 1 of 1

dasatinib

EPHB3Tchem Kinase

Kd: 8.16

Active Ligands (2)

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1 – 2 of 2

CHEMBL566515

EPHB3Tchem Kinase

IC50: 7.82000017

compound 20 [PMID: 23489211]

EPHB3Tchem Kinase

IC50: 5.36000013

Protein Data Bank (4)

1 – 4 of 4

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (14)

Reactome (5)

KEGG (1)

PathwayCommons (4)

WikiPathways (4)

Axon guidance (R-HSA-422475)

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5

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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

Gene Ontology Terms (39)

Functions (7)

Components (8)

Processes (24)

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10

1 – 7 of 7

GO Term	Evidence	Assigned by
protein tyrosine kinase activity	Inferred from Experiment (EXP)	Reactome
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
axon guidance receptor activity	Inferred from Electronic Annotation (IEA)	Ensembl

Protein-Protein Interactions (126)

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1 – 10 of 126

• See Interactions on String-DB

EFNB2

Tbio

Novelty: 0.00309066

p_int: 0.999988876

p_ni: 0.000011124

Score: 0.998

Data Source: BioPlex,STRINGDB

C16orf58

Tdark

Novelty: 0.00625312

p_int: 0.999584618

p_ni: 0.000414807

p_wrong: 5.74e-7

Score: 0.189

Data Source: BioPlex,STRINGDB

ADGRG5

Tdark

Family: GPCR

Novelty: 0.38877844

p_int: 0.998203905

p_ni: 0.001780833

p_wrong: 0.000015262

Score: 0.159

Data Source: BioPlex,STRINGDB

EFNA5

Tbio

Novelty: 0.00173565

Score: 0.997

Data Source: STRINGDB

EFNB3

Tbio

Novelty: 0.01171599

Score: 0.995

Data Source: STRINGDB

EFNB1

Tbio

Novelty: 0.00491089

Score: 0.995

Data Source: STRINGDB

EFNA3

Tbio

Novelty: 0.01717372

Score: 0.993

Data Source: STRINGDB

EFNA2

Tbio

Novelty: 0.0109729

Score: 0.992

Data Source: STRINGDB

EFNA4

Tbio

Novelty: 0.02322294

Score: 0.992

Data Source: STRINGDB

EFNA1

Tbio

Family: Kinase

Novelty: 0.00738582

Score: 0.992

Data Source: STRINGDB

Publication Statistics

PubMed Score  100.94

PubMed score by year

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PubTator Score  48.52

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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

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Structural Annotations

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UniProt Keyword Find Similar Targets

3D-structure
Angiogenesis
ATP-binding
Cell membrane
Cell projection
Complete proteome
Developmental protein
Disulfide bond
Glycoprotein
Kinase

GWAS Trait Find Similar Targets

nose morphology measurement

MGI Phenotype Find Similar Targets

cellular phenotype
nervous system phenotype