EGF domains are modular protein subunits found singly or in tandem, mostly in the extracellular milieu, where they are involved in a diverse array of functions. Intercellular signaling mediated by EGF-containing ligands and their cognate receptors are important regulators of growth and development. Many EGF-containing molecules, including human epidermal growth factor receptor family (HER tyrosine kinase receptor) ligands such as EGF and TGF-α, are shed from the surface by extracellular proteases, resulting in longer range extracellular signaling. EGF domains play an important structural role as a spacer at the cellular level.
Structurally, the EGF domain is typically described as a small domain of 30–40 amino acids primarily stabilized by three disulfides with disulfide connectivity ababcc. The EGF domain consists of two β-sheets, usually referred to as the major (N-terminal) and minor (C-terminal) sheets. The half-cystines of the abc motif are arranged in a triangle on the major sheet.
The EGF-like domain is an evolutionary conserved protein domain. The EGF-like domain is a sequence of about thirty to forty amino-acid residues long firstly found in the sequence of epidermal growth factor (EGF). It has been shown to be present, in a more or less conserved form, in a large number of proteins. The EGF-like domain contains six cysteines which form disulfide bonds within the domain (C1-C3, C2-C4, C5-C6).
It is suggested that EGF-like domains in laminin, in other ECM proteins and in the extracellular portions of some membrane proteins are signals for cellular growth and differentiation. Because they are integral parts of large molecules and often of supramolecular assemblies these domains are well suited to stimulate neighboring cells in a specific and vectorial way.