Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

EPHB3 (P54753) - Overview - Molecular Target Synopsis

Protein


EPHB3, Ephrin type-B receptor 3
Enzyme Classification 2.7.10.1
UniProt P54753

Also Known as EPHB3_HUMAN, EPHB3, ETK2, HEK2, TYRO6

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. Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses.

5L6O
EPHB3 KINASE DOMAIN COVALENTLY BOUND TO AN IRREVERSIBLE INHIBITOR (COMPOUND 3)
RCSB/PDB
Inspect Structure
See all 3D Structures for EPHB3

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
998ENSG00000182580ENST00000330394ENSP00000332118P54753-1

Drugs


EPHB3 is targeted by Approved Drug Vandetanib. (see details)
Vandetanib

Sub-cellular localization


UniProt: EPHB3 is active in the following subcellular-locations: cell membrane, cell projection, dendrite.
GO terms: EPHB3 is active in the following subcellular-locations: cytosol, dendrite, extracellular region, integral component of plasma membrane, neuron projection, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project EPHB3 has gain in 11 cell-lines, loss in 1 cell-lines and no signal in 992 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: COLO205, T47D, U251

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: LS 174T, MT-3, SW 1463

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, NHLF, A549

(see details)

RNA Interference


EPHB3 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: H1838, HOSMNNG. (see details)

3D Structures


For EPHB3 there are:
4 structures (7 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EPHB3 has been screened with 773 compounds (1386 bioactivities), 20 compounds have bioactivities that show binding affinity of <= 500nM (21 bioactivities). (see details)