Tchem EPHA4 Ephrin type-A receptor 4

Protein Summary

Description

Receptor tyrosine kinase which binds 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, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

Uniprot Accession IDs

• P54764
• A8K2P1
• B2R601
• B7Z6Q8
• Q2M380

Gene Name

• EPHA4

Ensembl ID

• ENST00000281821
• ENSP00000281821
• ENSG00000116106
• ENST00000409938
• ENSP00000386829

Symbol

• HEK8
• SEK
• TYRO1
• EK8
• SEK
• HEK8
• TYRO1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
protein domain	1
biological process	0.97
PubMedID	0.97
transcription factor perturbation	0.96

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Eph Family / Ephrin Type-a Receptor 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1846.85   (req: < 5)

Gene RIFs: 52   (req: <= 3)

Antibodies: 635   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1846.85   (req: >= 5)

Gene RIFs: 52   (req: > 3)

Antibodies: 635   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 48

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 15

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 2