EPH receptor A3

EPH receptor A3 is a protein that in humans is encoded by the EPHA3 gene. This gene is a member of 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.

Function

EPH receptor A3 plays a critical role in the regulation of cell migration, development, and assembly. The interaction of this receptor with its ephrin ligands located on adjacent cells leads to contact-dependent bidirectional signaling into neighboring cells. The signaling process is important for the development and function of many tissues, including the nervous system. EPH receptor A3 is involved in various developmental processes, particularly in the patterning of the neural system and in the development of other organ systems. It has also been implicated in the regulation of cancer cell behavior, influencing tumor growth, invasion, and metastasis.

Clinical Significance

Alterations in the expression of EPHA3 have been associated with several types of cancer, including lung, colorectal, and gastric cancers. The aberrant expression of EPH receptor A3 can contribute to the oncogenic process by affecting cell adhesion, migration, and invasion. As such, EPH receptor A3 is being studied as a potential target for cancer therapy. Inhibitors of EPH receptor A3 are being explored for their therapeutic potential to block tumor growth and spread.

Gene

The EPHA3 gene is located on human chromosome 3 at position 3p11.2. It spans approximately 100 kilobases and consists of 17 exons. The gene encodes a protein of 983 amino acids with a predicted molecular weight of approximately 108 kDa. The structure of the EPH receptor A3 protein includes an extracellular region with a globular domain, a cysteine-rich domain, two fibronectin type III domains, a transmembrane region, and a cytoplasmic region with a juxtamembrane domain, a kinase domain, a sterile alpha motif (SAM) domain, and a PDZ-binding motif.

Interaction

EPH receptor A3 interacts with its ligands, the ephrins, through its extracellular domain. This interaction initiates bidirectional signaling that affects both the receptor-expressing and the ligand-expressing cells. The receptor has been shown to interact with various intracellular proteins that mediate its signaling, including Src family kinases, which are involved in the regulation of cell adhesion and migration.

See Also

• EPH receptor
• Protein-tyrosine kinase
• Cancer
• Cell migration