Conserved Site

Tyrosine-protein kinase, receptor class V, conserved site (IPR001426)

Short name: Tyr_kinase_rcpt_V_CS

Description

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [PMID: 3291115]:

  • Serine/threonine-protein kinases
  • Tyrosine-protein kinases
  • Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human [PMID: 12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PMID: 12368087]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [PMID: 15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PMID: 15320712].

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups [PMID: 12471243]:

  • Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis [PMID: 19275641]. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction [PMID: 16700535].

  • Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [PMID: 15845350].

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 [PMID: 3052279]. These receptor tyrosine kinases (RTK) all share the same topology: an extracellular ligand-binding domain, a single transmembrane region and a cytoplasmic kinase domain and have been classified into at least five groups on the basis of sequence similarities.

The extracellular domain of class V RTK's has 16 conserved cysteine residues that are probably involved in disulphide bonds; this region is followed by two copies of a fibronectin type III domain. The ligands for these receptors are proteins known as ephrins. The EPHA subtype receptors bind to GPI-anchored ephrins while the EPHB subtype receptors bind to type-I membrane ephrins.

GO terms

Biological Process

GO:0006468 protein phosphorylation
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway

Molecular Function

GO:0005524 ATP binding
GO:0005003 ephrin receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns
PROSITE patterns