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

EPHA8 (P29322) - Overview - Molecular Target Synopsis

Protein


EPHA8, Ephrin type-A receptor 8
Enzyme Classification 2.7.10.1
UniProt P29322

Also Known as EPHA8_HUMAN, EPHA8, EEK, HEK3, KIAA1459

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. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth. 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. May also form heterodimers with other ephrin receptors (By similarity). Interacts with FYN; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PIK3CG; regulates integrin-mediated cell adhesion to substrate. Interacts with TIAM1; regulates clathrin-mediated endocytosis of EPHA8. Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-independent but stimulated by EPHA8 ubiquitination.

3KUL
KINASE DOMAIN OF HUMAN EPHRIN TYPE-A RECEPTOR 8 (EPHA8)
RCSB/PDB
Inspect Structure
See all 3D Structures for EPHA8

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
1005ENSG00000070886ENST00000166244ENSP00000166244P29322-1
495ENSG00000070886ENST00000374644, ENST00000538803ENSP00000363775, ENSP00000440274P29322-2

Drugs


EPHA8 is targeted by Approved Drug Vandetanib. (see details)
Vandetanib

Sub-cellular localization


UniProt: EPHA8 is active in the following subcellular-locations: cell membrane, cell projection, early endosome membrane.
GO terms: EPHA8 is active in the following subcellular-locations: early endosome membrane, integral component of plasma membrane, neuron projection, plasma membrane, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project EPHA8 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, MDA_MB_435, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: COLO-704, NCI-H82, SCLC-21H

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: SK-N-SH, NHLF, HSMM

(see details)

RNA Interference


EPHA8 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, HS578T. (see details)

3D Structures


For EPHA8 there are:
3 structures (4 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EPHA8 has been screened with 322 compounds (566 bioactivities), 15 compounds have bioactivities that show binding affinity of <= 500nM (24 bioactivities). (see details)