{PDOC51550}
{PS51550; EPH_LBD}
{BEGIN}
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* Eph receptor ligand binding (Eph LBD) domain profile *
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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 alpha 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 beta-sandwich   composed   of   11  antiparallel  beta-strands  (see
<PDB:1NUK>). It  has  two antiparallel beta-sheets, with the usual left-handed
twist, packed  against each other to form a compact beta-sandwich, and a short
3(10) helix [1,2,3].

The profile we developed covers the entire Eph LBD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: October 2011 / First entry.

[ 1] Himanen J.-P., Henkemeyer M., Nikolov D.B.
     "Crystal structure of the ligand-binding domain of the receptor
     tyrosine kinase EphB2."
     Nature 396:486-491(1998).
     PubMed=9853759; DOI=10.1038/24904
[ 2] Himanen J.-P., Rajashankar K.R., Lackmann M., Cowan C.A.,
     Henkemeyer M., Nikolov D.B.
     "Crystal structure of an Eph receptor-ephrin complex."
     Nature 414:933-938(2001).
     PubMed=11780069; DOI=10.1038/414933a
[ 3] Himanen J.-P., Goldgur Y., Miao H., Myshkin E., Guo H., Buck M.,
     Nguyen M., Rajashankar K.R., Wang B., Nikolov D.B.
     "Ligand recognition by A-class Eph receptors: crystal structures of
     the EphA2 ligand-binding domain and the EphA2/ephrin-A1 complex."
     EMBO Rep. 10:722-728(2009).
     PubMed=19525919; DOI=10.1038/embor.2009.91

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