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

EPHA3 (P29320) - Overview - Molecular Target Synopsis

Protein


EPHA3, Ephrin type-A receptor 3
Enzyme Classification 2.7.10.1
UniProt P29320

Also Known as EPHA3_HUMAN, EPHA3, ETK, ETK1, HEK, TYRO4

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. 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. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling (By similarity). Interacts (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling through RHOA GTPase activation.

4TWO
HUMAN EPHA3 KINASE DOMAIN IN COMPLEX WITH COMPOUND 164
RCSB/PDB
Inspect Structure
See all 3D Structures for EPHA3

Isoforms / Transcripts (Protein Coding)


Drugs


EPHA3 is targeted by Approved Drug Vandetanib. (see details)
Vandetanib

Sub-cellular localization


UniProt: EPHA3 is active in the following subcellular-locations: cell membrane, secreted.
GO terms: EPHA3 is active in the following subcellular-locations: early endosome, 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 EPHA3 has gain in 3 cell-lines, loss in 10 cell-lines and no signal in 992 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_19, MDA_MB_435, U251

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1581, NCI-H446, COLO 699

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: GM12878, SK-N-SH, NHLF

(see details)

RNA Interference


EPHA3 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, SUM44. (see details)

3D Structures


For EPHA3 there are:
27 structures (27 chains) solved
15 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EPHA3 has been screened with 722 compounds (1344 bioactivities), 19 compounds have bioactivities that show binding affinity of <= 500nM (25 bioactivities). (see details)