{PDOC01003}
{PS01299; EPHRIN_RBD_1}
{PS51551; EPHRIN_RBD_2}
{BEGIN}
*********************************************************************
* Ephrin receptor-binding (ephrin RBD) domain signature and profile *
*********************************************************************

Ephrins are a family of proteins [1] that are ligands of class V (EPH-related)
receptor protein-tyrosine  kinases  (see <PDOC00629>). Initially identified as
regulators of  axon pathfinding and neuronal cell migration, the Eph receptors
and their  ephrin  ligands are now known to have roles in many other cell-cell
interactions, including  those  of  vascular endothelial cells and specialized
epithelia [2].

Ephrins are  membrane-attached  proteins  of  205  to 340 residues. Attachment
appears to be crucial for their normal function. Type-A ephrins  are linked to
the membrane  via  a  GPI  linkage,  while  type-B ephrins are type-I membrane
proteins.

The globular  ephrin  receptor-binding  domain  (ephrin  RBD) is a beta barrel
composed of  eight  strands  arranged  in two sheets around a hydrophobic core
(see <PDB:1IKO>).  Interspersed between beta strands are two alpha helices and
one 3(10)  helix.  The  sheets are composed of mixed parallel and antiparallel
beta strands  arranged  in  a  Greek  key  topology.  Like  other cell-surface
proteins, ephrins  contain  disulfide  bonds  to enhance stability. Two buried
disulfide bonds are present: one pair holds together beta strands C and F, and
the other  pair  anchors  two small helices, E and I, at the top of the barrel
[2,3].

We developed  both  a  pattern  and  a  profile for the ephrin RBD domain. The
profile covers the entire ephrin RBD domain.

-Consensus pattern: [KRQ]-[LF]-[CST]-x-K-[IF]-Q-x-[FY]-[ST]-[PA]-x(3)-G-x-E-F-
                    x(5)-[FY](2)-x(2)-[SA]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: October 2011 / Text revised; profile added.

[ 1] Kozlosky C.J., Maraskovsky E., McGrew J.T., Vandenbos T., Teepe M.,
     Lyman S.D., Srinivasan S., Fletcher F.A., Gayle R.B. III, Cerretti D.P.,
     Beckmann M.P.
     "Ligands for the receptor tyrosine kinases hek and elk: isolation of
     cDNAs encoding a family of proteins."
     Oncogene 10:299-306(1995).
     PubMed=7838529
[ 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] Toth J., Cutforth T., Gelinas A.D., Bethoney K.A., Bard J.,
     Harrison C.J.
     "Crystal structure of an ephrin ectodomain."
     Dev. Cell 1:83-92(2001).
     PubMed=11703926

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}