{PDOC00629}
{PS00790; RECEPTOR_TYR_KIN_V_1}
{PS00791; RECEPTOR_TYR_KIN_V_2}
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* Receptor tyrosine kinase class V signatures *
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A number of growth factors  stimulate mitogenesis by interacting with a family
of   cell  surface receptors which   possess  an  intrinsic, ligand-sensitive,
protein tyrosine kinase activity [1].   These  receptor tyrosine kinases (RTK)
all share the same topology: an  extracellular ligand-binding domain, a single
transmembrane  region and a cytoplasmic  kinase domain.   However  they can be
classified into at  least  five groups on the basis of  sequence similarities.
The extracellular domain of class V RTK's consist  of  a  region  of about 300
amino acids,  amongst  which  16  conserved    cysteines  probably involved in
disulfide bonds;  this  region is followed by two copies of a fibronectin type
III domain.  The ligands  for these receptors are proteins of about 200 to 300
residues collectively  known  as  Ephrins  (see  <PDOC01003>).  The  receptors
currently known to belong to class V are [2,3,E1]:

 - EPHA1 (Eph-1; Esk).
 - EPHA2 (Eck; Mpk-5; Sek-2).
 - EPHA3 (Etk-1; Hek; Mek4; Tyro4; Rek4; Cek4).
 - EPHA4 (Sek; Hek8; Mpk-3; Cek8).
 - EPHA5 (Ehk-1; Hek7; Bsk; Cek7).
 - EPHA6 (Ehk-2).
 - EPHA7 (Ehk-3; Hek11; Mdk-1; Ebk).
 - EPHA8 (Eek).
 - EPHB1 (Eph-2; Elk; Net).
 - EPHB2 (Eph-3; Hek5; Drt; Erk; Nuk; Sek-3; Cek5; Qek5).
 - EPHB3 (Hek-2; Mdk-5).
 - EPHB4 (Htk; Mdk-2; Myk-1).
 - EPHB5 (Cek9).
 - EPHB6 (HEP).

The EPHA subtype receptors bind to GPI-anchored ephrins while the EPHB subtype
receptors bind to type-I membrane ephrins.

We developed  two  signature  patterns  for  this  class  of RTK's, which each
include some of the conserved cysteine residues.

-Consensus pattern: F-x-[DN]-x-[GAW]-[GAS]-C-[LIVM]-[SA]-[LIVM](2)-[SA]-[LV]-
                    [KRHQ]-[LIVA]-x(3)-[KREQT]-C-[PSAWR]
                    [The 2 C's may be involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: C-x(2)-[DE]-G-[DEQKRG]-W-x(2,3)-[PAQ]-[LIVMT]-[GT]-x-C-
                    x-C-x(2)-G-[HFY]-[EQ]
                    [The 3 C's may be involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2006 / Pattern revised.

[ 1] Yarden Y., Ullrich A.
     "Growth factor receptor tyrosine kinases."
     Annu. Rev. Biochem. 57:443-478(1988).
     PubMed=3052279; DOI=10.1146/annurev.bi.57.070188.002303
[ 2] Sajjadi F.G., Pasquale E.B., Subramani S.
     "Identification of a new eph-related receptor tyrosine kinase gene
     from mouse and chicken that is developmentally regulated and encodes
     at least two forms of the receptor."
     New Biol. 3:769-778(1991).
     PubMed=1657122
[ 3] Wicks I.P., Wilkinson D., Salvaris E., Boyd A.W.
     "Molecular cloning of HEK, the gene encoding a receptor tyrosine
     kinase expressed by human lymphoid tumor cell lines."
     Proc. Natl. Acad. Sci. U.S.A. 89:1611-1615(1992).
     PubMed=1311845
[E1] http://depts.washington.edu/eph/

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