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

EPHA2 (P29317) - Overview - Molecular Target Synopsis

Protein


EPHA2, Ephrin type-A receptor 2
Enzyme Classification 2.7.10.1
UniProt P29317

Also Known as EPHA2_HUMAN, EPHA2, ECK

Receptor tyrosine kinase which binds promiscuously membrane-bound 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis., (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. Homodimer. Interacts with SLA. Interacts (phosphorylated form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3); critical for the EFNA1-induced activation of RAC1 which stimulates cell migration (By similarity). Interacts with INPPL1; regulates activated EPHA2 endocytosis and degradation. Interacts (inactivated form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16, DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4 and may regulate tight junctions. Interacts with ACP1. Interacts (via SAM domain) with ANKS1A (via SAM domain). Interacts with CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell migration and adhesion.

6NK2
EPHA2 LBD IN COMPLEX WITH BA-WLA-YRPK BIO PEPTIDE
RCSB/PDB
Inspect Structure
See all 3D Structures for EPHA2

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
976ENSG00000142627ENST00000358432ENSP00000351209P29317-1
497P29317-2

Drugs


EPHA2 is targeted by Approved Drugs Dasatinib, Vandetanib. (see details)
Dasatinib
Vandetanib

Sub-cellular localization


UniProt: EPHA2 is active in the following subcellular-locations: cell junction, cell membrane, cell projection, focal adhesion, lamellipodium membrane, ruffle membrane.
GO terms: EPHA2 is active in the following subcellular-locations: cell surface, focal adhesion, integral component of plasma membrane, lamellipodium, lamellipodium membrane, leading edge membrane, neuron projection, plasma membrane, receptor complex, ruffle membrane, tight junction.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project EPHA2 has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_3, PC_3, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-74, COV318, HCC366

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, A549, HUVEC

(see details)

RNA Interference


EPHA2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: 93VU, H23. (see details)

3D Structures


For EPHA2 there are:
63 structures (95 chains) solved
41 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

EPHA2 is solved in complex with the approved drug(s):

1N1/DASATINIB (5I9Y_A),
DB8/BOSUTINIB (5I9X_A),
ACA/AMINOCAPROIC ACID (6NK0_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EPHA2 has been screened with 1510 compounds (2262 bioactivities), 280 compounds have bioactivities that show binding affinity of <= 500nM (288 bioactivities). (see details)