PROSITE documentation PDOC00629
Receptor tyrosine kinase class V signatures


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.

Last update:

April 2006 / Pattern revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

RECEPTOR_TYR_KIN_V_1, PS00790; Receptor tyrosine kinase class V signature 1  (PATTERN)

RECEPTOR_TYR_KIN_V_2, PS00791; Receptor tyrosine kinase class V signature 2  (PATTERN)


1AuthorsYarden Y. Ullrich A.
TitleGrowth factor receptor tyrosine kinases.
SourceAnnu. Rev. Biochem. 57:443-478(1988).
PubMed ID3052279

2AuthorsSajjadi F.G. Pasquale E.B. Subramani S.
TitleIdentification 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.
SourceNew Biol. 3:769-778(1991).
PubMed ID1657122

3AuthorsWicks I.P. Wilkinson D. Salvaris E. Boyd A.W.
TitleMolecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines.
SourceProc. Natl. Acad. Sci. U.S.A. 89:1611-1615(1992).
PubMed ID1311845


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 prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)