|PROSITE documentation PDOC51550|
The Eph receptors, which bind a group of cell-membrane-anchored ligands known as ephrins, represent the largest subfamily of receptor tyrosine kinases (RTKs) (see <PDOC00629>). The Eph receptors and their ephrin ligands control a diverse array of cell-cell interactions in the nervous and vascular systems. On ephrin binding, the Eph kinase domain is activated, initiating 'forward' signaling in the receptor-expressing cells. Simultaneously, signals are also induced in the ligand-expressing cells a phenomenon referred to as 'reverse' signalling. The extracellular Eph receptor region contains a conserved 180-amino-acid N-terminal ligand-binding domain (LBD) which is both necessary and sufficient for bindings of the receptors to their ephrin ligands. An adjacent cysteine-rich region might be involved in receptor-receptor oligomerization often observed on ligand binding, whereas the next two fibronectin type III repeats (see <PDOC50853>) have yet to be assigned a clear biological function. The cytoplasmic Eph receptor region contains a kinase domain (see <PDOC00100>), a sterile α motif (SAM) domain (see <PDOC50105>), and a PDZ-binding motif. The ligand-binding domain (LBD) of Eph receptors is unique to this family of RTKs ans shares no significant amino-acid-sequence homology with other known proteins [1,2,3].
The Eph LBD domain forms a compact globular structure which folds into a jellyroll β-sandwich composed of 11 antiparallel β-strands (see <PDB:1NUK>). It has two antiparallel β-sheets, with the usual left-handed twist, packed against each other to form a compact β-sandwich, and a short 3(10) helix [1,2,3].
The profile we developed covers the entire Eph LBD domain.Last update:
October 2011 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Himanen J.-P. Henkemeyer M. Nikolov D.B.|
|Title||Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2.|
|2||Authors||Himanen J.-P. Rajashankar K.R. Lackmann M. Cowan C.A. Henkemeyer M. Nikolov D.B.|
|Title||Crystal structure of an Eph receptor-ephrin complex.|
|3||Authors||Himanen J.-P. Goldgur Y. Miao H. Myshkin E. Guo H. Buck M. Nguyen M. Rajashankar K.R. Wang B. Nikolov D.B.|
|Title||Ligand recognition by A-class Eph receptors: crystal structures of the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex.|
|Source||EMBO Rep. 10:722-728(2009).|