Function: Receptor for members of the ephrin-A family. Binds to ephrin-A1, -A3, -A4 and -A5. Plays an important role in angiogenesis and tumor neovascularization. The recruitement of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly (By similarity). Induces apoptosis in a p53/TP53-independent, caspase-8-dependent manner. Tissue specificity: Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g., skin, intestine, lung, and ovary. Disease: Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:613020]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision. Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:116600]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity. Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. Contains 2 fibronectin type-III domains. Contains 1 protein kinase domain. Contains 1 SAM (sterile alpha motif) domain. PTM: Activated by EFNA1 via tyrosine phosphorylation. Phosphorylated residues Tyr-588 and Tyr-594 are required for binding VAV2 and VAV3 while phosphorylated residues Tyr-735 and Tyr-930 are required for binding PI3-kinase p85 subunit. These phosphorylated residues are critical for recruitment of VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream signaling to activate RAC1 GTPase and endothelial cell migration. They also play a critical role in transducing EPHA2 signaling in vascular endothelial cells during tumor angiogenesis.