EphB6 is located on chromosome 7q33-q35.

Size: 16056 bases.
Orientation: plus strand.

EphB6 mRNA size is 4044 bp.

Not reported.

The crystal structure of EphB6 has not yet been determined. However, based on amino acid sequence and domain arrangement it is classified as a type I transmembrane protein. It has a highly conserved N-terminal domain in the extracellular region that is involved in ligand recognition and binding (Labrador et al., 1997). The N-terminal domain is followed by a cysteine rich region and two fibronectin type-III repeats. These repeats are involved in mediating protein-protein interactions and receptor dimerization (Lackmann et al., 1998). The intracellular region contains a juxtamembrane domain, a conserved kinase domain, a sterile α-motif (SAM) domain and a PSD95/Dlg/ZO1 (PDZ) domain (Kalo and Pasquale, 1999).

Eph (erythropoietin producing hepatocellular carcinoma) receptors belong to a family of receptor tyrosine kinases, which are activated by binding to ephrin ligands. These receptors are involved in a diverse array of signal transduction processes in humans. Such diversity of signaling and the resulting functional output is partly attributed to differential expression and interactions among these receptors. Based on sequence homology and affinity for ephrin ligands, Eph receptors are classified into A and B groups. EphB6 is a kinase-deficient receptor (Gurniak and Berg, 1996) that has been shown to interact with two kinase-active receptors, namely, EphB2 and EphA2 (Fox and Kandpal, 2011). Ephrin B2 has been reported as a ligand for this receptor (Munthe et al., 2000). The loss of EphB6 expression in breast carcinoma cell lines has been correlated to their invasiveness (Fox and Kandpal, 2004; Fox and Kandpal, 2006), and its role as a tumor suppressor has also been reported (Fox and Kandpal, 2009; Yu et al., 2010).

Eph receptors are expressed in a wide variety of tissues and cells (Andres et al., 1994; Fox et al., 1995; Ciossek et al., 1995; Lickliter et al., 1996; Muñoz et al., 2002). In addition to other tissues and cells, EphB6 receptor expression has been shown in breast, prostate, thymus, mature T-cells and leukemia cells (Shimoyama et al., 2000; Luo et al., 2001; Luo et al., 2002; Fox and Kandpal, 2004; Fox et al., 2006). EphB6 deficient mice develop normally and do not display any abnormality in their general appearance (Shimoyama et al., 2002).

Cellular. EphB6 is a transmembrane protein.

A variety of Eph receptors and their ligands are involved in regulating cell pattern formation during organogenesis (Xu and Wilkinson, 1997; Flanagan and Vanderhaeghen, 1998; Holmberg et al., 2000; Leighton et al., 2001; Kullander et al., 2001; Gerlai, 2001). EphB6 has been shown to facilitate T-cell activation (Luo et al., 2002). Metastasis/invasion suppressor role of EphB6 in non-small cell lung carcinoma and breast carcinoma (Müller-Tidow et al., 2005; Fox and Kandpal, 2009) suggests its involvement in cell adhesion and migration.

Amino acid homology between EphB6 and other EphB family members varies between 47% and 60%. Mouse and human homologs of EphB6 share greater than 90% amino acid identity (Gurniak and Berg, 1996; Matsuoka et al., 1997). The kinase domain in EphB6 is mutated.