The EPHA2 is composed of 17 exons and 16 intervening introns spanning in a region of 31,73 kb.

The transcribed mRNA was 3970 bp (NM_004431).

EPHA2 receptor is a transmembrane glycoprotein composed of 976 amino acid residues, with a calculated molecular mass of 130 kDa and an isoelectric point 6.1398. It is one member of the largest EPH (erythropoietin-producing hepatoma amplified sequence) family receptor tyrosine kinases. The family of Eph kinases binds ligands (known as ephrins) that are anchored to the membrane adjacent cells and consists of 16 known members across species, 14 of which are found in mammals and characterized by shared features in both the extracellular and intracellular domains.
EPH class receptors contain a single transmembrane spanning domain. Like other receptor tyrosine kinases, the extracellular domain of EPHA2 mediates ligand binding whereas the intacellular domain possesses intrinsic enzymatic activity.
The extracellular domain is glycosylated and is composed of globular, amino terminal domain followed by a cysteine-rich region with an epidermal growth factor-like motif and two fibronectin III-type repeats. The globular, amino-terminal domain contains immunoglobulin-like motifs and is both necessary and sufficient for ephrin-binding.
The intracellular domain includes a juxtamembrane region, a tyrosine kinase domain, a sterile alpha motif (SAM) and a PDZ-binding motif in the carboxy terminal end. The kinase domain and juxtamembrane region contain tyrosine residues and phosphorylation of these tyrosine residues creates docking sites for interaction with signalling proteins containing SH2/SH3 (Src - homology - 2/3) domains. SAM domain forms homodimers and may regulate receptor dimerization. The PDZ-binding motif binds to PDZ domain-containing proteins, which are though to serve as scaffolds for the assembly of multi-protein signalling complexes at the membrane.
EPHA2 shows 25-35% sequence homologies with other EPH receptors, and the tyrosine residues are conserved within the juxtamembrane and kinase domain.

EPHA2 is largely restricted at low levels on adult proliferating epithelial cells and enriched within sites of cell-cell adhesion in normal epithelial cells. EPHA2 expression has been detected in the brain, skin, bone marrow, lung, thymus, small intestine, colon, urinary bladder, kidney, liver, spleen, uterus, testis and prostate. EPHA2 expression levels in the colon, skin, kidney and lung were over 10-fold compared to those of the bone marrow. EPHA2 is also expressed during gastrulation in the ectodermal cells and early embryogenesis in the developing hind brain. In the skin, EphA2 is present in keratinocytes of epidermis and hair follicles but not in dermal cells, such as fibroblasts, vascular cells and inflammatory cells. EPHA2 has also been detected in proliferating mammary glands in female mice at puberty and differentially expressed during the estrous cycle. EPHA2 is widely unregulated and functionally altered in a variety of carcinomas and is implicated in cell transformation, primary tumor initiation, angiogenesis and metastasis in advanced cancer models. Overexpression has been shown both at the mRNA and protein level in established cell lines and human clinical specimens. Consistent findings indicate the prevalence of EPHA2 overexpression in many cancers, including glioblastoma, colorectal, gastric, esophageal, breast, thyroid, ovarian, endometrial, cervical, pancreatic, prostate, melanoma, bladder, renal cell, lung and hepatocellular carcinoma.

The EPHA2 is localized to the cell membrane.

The ligands for the EPH receptors are ephrins, which are 9 members and also fall into 2 subclasses: the GPI (glycosylphosphatidylinositol) anchored A-class of ligands (Ephrin A1-6) and the transmembrane B-class of ligands (B1-3).
EPH receptors interact with their cognate membrane anchored ligands at cell-cell contact sites to activate bidirectional signaling pathways effecting diverse physiologic processes including cell adhesion, repulsion, morphology, migration, differentiation and proliferation. Specifically, EPHA2 is activated by the ligand ephrin A1/EFNA1 and regulates migration, proliferation, integrin-mediated adhesion and differentiation of cells.
EPH receptor signaling has been implicated in many biological processes such as axon guidance and fasciculation, tissue border formation, neuronal targeting and angiogenesis during embryonic development. Especially, EPHA2 is involved in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. EPHA2 with ephrin A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. It also engaged with the ephrin A5/EFNA5 and may regulate lens fiber cells shape and interactions and be critical for lens transparency development and maintenance.
Emerging evidence implicates EPHA2 overexpression in cell transformation, primary tumor initiation, progression, angiogenesis and metastasis in a variety of cancer models.

Human EPHA2 shares 96% amino acid identity with the chimpanzee, 95% amino acid identity with dogs, 94% with cows, 93% with mouse, 92% with rats and 56% amino acid identity with zebrafish.

Congenital cataract (CC) is one of the most significant causes of visual impairment and blidness in childhood. Approximately, up to 25% of all CC could be inherited, most often transmitting as an autosomal dominant trait and showing considerable inter- and intra-familial phenotypic variation.

Loci for autosomal dominant posterior polar CC and total CC have both been mapped to chromosom 1p36 harboring the EPHA2 gene. Two missense mutations and one frameshift in the EPHA2 gene have been linked with posterior polar CC and one splicing mutation have been associated with total CC.
The c.2819 C>T (p.T940I) missense mutation changes an oligomerization interface of the SAM domain, most likely inactivating the EPHA2 signalling function by destroying its SAM domain.
The c.2842 G>T (p.G648W) missense mutation identified in exon 17 and occured at the first base of codon 948 and was predicted to result in substitution of glycine to tryptophan at the level of translation, placing it in the cytoplasmic SAM domain of EPHA2 gene.
The c.2915_2916delTG deletion of 2 bp discovered in exon 7 of EPHA2 gene and was predicted to result in a frameshift mutation creating a mutant protein with a novel C-terminal polypeptide of 39 amino acid residues.
The c.2826-9G>A is a splicing mutation with a single base substitution in intron 16 which creates a novel splice acceptor site causing an intronic sequence of 7 bp to be included in the processed transcript. This aberrant splicing is predicted to result in translational of a novel C-terminal polypeptide of 71 amino acid residues of which the last 39 are identical to that of the nove polypeptide produced bt the c.2915_2916delTG.