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	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.

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

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

• 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 in UniProtKB/Swiss-Prot known to belong to this class: 52
  • detected by PS00790: 49 (true positives)
  • undetected by PS00790: 3 (1 false negative and 2 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00790:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00790
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00790
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00790
• View ligand binding statistics of PS00790
• Matching PDB structures: 1KGY 1SHW 2X10 2X11 ... [ALL]

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

• 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 in UniProtKB/Swiss-Prot known to belong to this class: 52
  • detected by PS00791: 51 (true positives)
  • undetected by PS00791: 1 (0 false negative and 1 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00791:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00791
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00791
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00791
• View ligand binding statistics of PS00791
• Matching PDB structures: 2X10 2X11 3FL7 3MBW ... [ALL]

1	Authors	Yarden Y., Ullrich A.
	Title	Growth factor receptor tyrosine kinases.
	Source	Annu. Rev. Biochem. 57:443-478(1988).
	PubMed ID	3052279
	DOI	10.1146/annurev.bi.57.070188.002303

2	Authors	Sajjadi F.G., Pasquale E.B., Subramani S.
	Title	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.
	Source	New Biol. 3:769-778(1991).
	PubMed ID	1657122

3	Authors	Wicks I.P., Wilkinson D., Salvaris E., Boyd A.W.
	Title	Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines.
	Source	Proc. Natl. Acad. Sci. U.S.A. 89:1611-1615(1992).
	PubMed ID	1311845

E1

Source

http://depts.washington.edu/eph/

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