EPHA2
Description
The EPHA2 (EPH receptor A2) is a protein-coding gene located on chromosome 1.
EPH receptor A2 (ephrin type-A receptor 2) is a protein that in humans is encoded by the EPHA2 gene. 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 two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. It may be implicated in BRAF mutated melanomas becoming resistant to BRAF-inhibitors and MEK inhibitors. It is also the receptor by which Kaposi's sarcoma-associated herpesvirus (KSHV) enters host cells; small molecule inhibitors of EphA2 have shown some ability to block KSHV entry into human cells. EPH receptor A2 has been shown to interact with: Ephrin A1, ACP1, Grb2, PIK3R1, and SHC1. It was also shown that doxazosin is a small molecule agonist of EPH receptor A2.
EPHA2 is a receptor tyrosine kinase that binds to membrane-bound ephrin-A family ligands on neighboring cells, initiating contact-dependent bidirectional signaling. This signaling process involves 'forward' signaling, triggered by the receptor, and 'reverse' signaling, initiated by the ephrin ligand. EPHA2 activation by ephrin-A1 (EFNA1) influences cell migration, integrin-mediated adhesion, proliferation, and differentiation. It regulates cell adhesion and differentiation through desmoglein-1 (DSG1) and inhibition of the ERK1/ERK2 (MAPK3/MAPK1) signaling pathway. Additionally, EPHA2 may be involved in UV radiation-induced apoptosis and exhibits a ligand-independent stimulatory effect on chemotactic cell migration. During development, EPHA2 plays a role in pattern formation and the development of various fetal tissues, including angiogenesis, early hindbrain development, and epithelial proliferation and branching morphogenesis during mammary gland development. Interaction with ephrin-A5 (EFNA5) influences lens fiber cell shape and interactions, contributing to lens transparency development and maintenance. In conjunction with ephrin-A2 (EFNA2), EPHA2 participates in bone remodeling by regulating osteoclastogenesis and osteoblastogenesis.
EPHA2 is also known as ARCC2, CTPA, CTPP1, CTRCT6, ECK.
