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Description

Ephrin type-A receptor 2 (UniProt: P29317, also known as EC: 2.7.10.1, Epithelial cell kinase, Tyrosine-protein kinase receptor ECK) is encoded by the EPHA2 (also known as ECK) gene (Gene ID: 1969) in human. Ephrin type-A receptor 2 is a homodimeric single-pass type I membrane protein that is expressed in brain and glioma tissue and in glioma cell lines. It is also highly expressed in tissues that contain a high proportion of epithelial cells. Its levels are shown to be up-regulated by UV irradiation via a TP53-independent, MAPK-dependent mechanism. Ephrin type-A receptor 2 serves as a receptor tyrosine kinase that binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. It is involved in the regulation of migration, integrin-mediated adhesion, and in proliferation and differentiation of cells. Ephrin type-A receptor 2 is phosphorylated on tyrosine residues upon binding and activation by EFNA1. Phosphorylation on Tyr 588 and Tyr 594 is reported to be essential for binding VAV2 and VAV3 while phosphorylation on Tyr 735 and Tyr 930 are required for binding PI3-kinase p85 subunit. It is synthesized with a signal peptide (aa 1-23) that is cleaved off in the mature form. The mature form has an extracellular domain (aa 24-537), a short transmembrane domain (aa 538-558), and a cytoplasmic domain (aa 559-976). Two isoforms of Ephrin type-A receptor 2 have been described that are produced by alternative splicing. EphA2 is reported to be overexpressed in skin tumors murine models and its overexpression may represent a compensatory feedback mechanism during tumorigenesis. (Ref.: Guo, H., et al. (2006). Cancer Res. 66(14), 7050-7058).