This entry represents the ligand-binding domain found in ephrin type-B receptor 2 (EphB2). EphB2 plays a role in cell positioning in the gastrointestinal tract by being expressed in proliferating progenitor cells []. It also has been implicated in colorectal cancer [, ]. A loss of EphB2, as well as EphA4, also precedes memory decline in a murine model of Alzheimers disease [].Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EhpB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands [].Ephrin receptors (EphRs) comprise the largest subfamily of receptor tyrosine kinases (RTKs). EphRs contain a ligand binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyrosine kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling) [].
Sterile alpha motif (SAM) domains are known to be involved in diverse protein-protein interactions, associating with both SAM-containing and non-SAM-containing proteins pathway []. SAM domains exhibit a conserved structure, consisting of a 4-5-helical bundle of two orthogonally packed alpha-hairpins. However SAM domains display a diversity of function, being involved in interactions with proteins, DNA and RNA []. The name sterile alpha motif arose from its presence in proteins that are essential for yeast sexual differentiation. The SAM domain has had various names, including SPM, PTN (pointed), SEP (yeast sterility, Ets-related, PcG proteins), NCR (N-terminal conserved region) and HLH (helix-loop-helix) domain, all of which are related and can be classified as SAM domains.SAM domains occur in eukaryotic and in some bacterial proteins. Structures have been determined for several proteins that contain SAM domains, including Ets-1 transcription factor, which plays a role in the development and invasion of tumour cells by regulating the expression of matrix-degrading proteases []; Etv6 transcription factor, gene rearrangements of which have been demonstrated in several malignancies []; EphA4 receptor tyrosine kinase, which is believed to be important for the correct localization of a motoneuron pool to a specific position in the spinal cord []; EphB2 receptor, which is involved in spine morphogenesis via intersectin, Cdc42 and N-Wasp []; p73, a p53 homologue involved in neuronal development []; and polyhomeotic, which is a member of the Polycomb group of genes (Pc-G) required for the maintenance of the spatial expression pattern of homeotic genes [].
