Recombinant Human Ephrin type-A receptor 3 (EPHA3), partial (Active)

Function

Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling (PubMed:11870224, PubMed:12794130). Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5 (By similarity). Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration (PubMed:11870224). Also activated by EFNA1, inhibiting epithelial-to-mesenchymal transition of cardiac cells and playing a role in heart development (PubMed:12794130). Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development (By similarity)

Subcellular Location

Secreted

Disease Association

Colorectal cancer (CRC) : A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. [The gene represented in this entry may be involved in disease pathogenesis]

Tissue Specificity

Widely expressed. Highest level in placenta

Subunit

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling (By similarity). Interacts (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts (phosphorylated) with CRK; mediates EFNA5-EPHA3 signaling through RHOA GTPase activation

• Wicks I.P. et al. Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines. — Proc. Natl. Acad. Sci. U.S.A. (1992)
• Chiari R. et al. Identification of a tumor-specific shared antigen derived from an Eph receptor and presented to CD4 T cells on HLA class II molecules. — Cancer Res. (2000)
• Boyd A.W. et al. Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. — J. Biol. Chem. (1992)
• Unified nomenclature for Eph family receptors and their ligands, the ephrins. — Cell (1997)
• Lawrenson I.D. et al. Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. — J. Cell Sci. (2002)
• Sharfe N. et al. Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation in T cells. — J. Immunol. (2003)
• Bardelli A. et al. Mutational analysis of the tyrosine kinome in colorectal cancers. — Science (2003)
• Smith F.M. et al. Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen. — J. Biol. Chem. (2004)