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

EPHB4 (P54760) - Overview - Molecular Target Synopsis

Protein


EPHB4, Ephrin type-B receptor 4
Enzyme Classification 2.7.10.1
UniProt P54760

Also Known as EPHB4_HUMAN, EPHB4, HTK, MYK1, TYRO11

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. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis. 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.

6FNI
CRYSTAL STRUCTURE OF EPHRIN B4 (EPHB4) RECEPTOR PROTEIN KINASE WITH NVP-BHG712
RCSB/PDB
Inspect Structure
See all 3D Structures for EPHB4

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
987ENSG00000196411ENST00000358173ENSP00000350896P54760-1
935ENSG00000196411ENST00000360620ENSP00000353833
516P54760-2
414P54760-4
306P54760-3

Drugs


EPHB4 is targeted by Approved Drug Vandetanib. (see details)
Vandetanib

Sub-cellular localization


UniProt: EPHB4 is active in the following subcellular-locations: cell membrane.
GO terms: EPHB4 is active in the following subcellular-locations: cytosol, extracellular exosome, 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 EPHB4 has gain in 7 cell-lines, loss in 1 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, PC_3, MDA_MB_231

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SNU-719, EPLC-272H, IM-95

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, HUVEC, HMEC

(see details)

RNA Interference


EPHB4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MCF12A, OVAS. (see details)

3D Structures


For EPHB4 there are:
23 structures (27 chains) solved
18 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

EPHB4 is solved in complex with the approved drug(s):

1N1/DASATINIB (6FNM_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EPHB4 has been screened with 1433 compounds (2267 bioactivities), 193 compounds have bioactivities that show binding affinity of <= 500nM (281 bioactivities). (see details)