The EGF-like domain includes 6 cysteine residues which in the epidermal growth factor have been shown to form 3 disulfide bonds.

[4] The differentiation of cEGF-like and hEGF-like domains and their subtypes is based on structural features and the connectivity of their disulfide bonds.

cEGF- and hEGF-like domains have a distinct shape and orientation of the minor sheet and one C-terminal half-cystine has a different position.

The differentiation of cEGF into subtype 1 and 2, which probably occurred after its split from hEGF, is based on different residue numbers between the distinct half-cystines.

The biological role of this post-translational modification is unclear,[4] but mice with a knockout of the aspartyl-β-hydroxylation enzyme show developmental defects.

In addition to the aforementioned three disulfide hEGF- and cEGF-like types, there are proteins carrying a four-disulfide EGF-like domain like laminin and integrin.

[4] The two main EGF-like domain subtypes hEGF and cEGF are not just distinct in their structure and conformation but also have different functions.

Kansas and co-workers were able to show that the EGF-like domain is not required for maximal cellular adhesion in L-selectin (expressed on lymphocytes).

[8] Immature human dendritic cells appear to require interactions with the EGF-like domains of selectins during their maturation process.

[10] Phan et al. could show that the artificial insertion of an N-glycosylation site into the EGF-like domains in P- and L-selectins increased the affinities of selectins to their ligands and led to slower rolling.

In conclusion, the EGF-like domain appears to play a vital role in immune responses as well as in eliminating dead cells in the organism.

Coordination of calcium strongly correlates with an unusual posttranslational modification of cbEGF-like domains: either an asparagine or aspartate is beta-hydroxylated giving rise to erythro-beta-hydroxyasparagine (Hyn) or erythro-beta-hydroxyaspartic acid (Hya), respectively.

Glycosylation in the form of O-linked di- or trisaccharides may occur at a serine residue between the first two cysteines of blood coagulation factors VII and IX.

[20] Multiple cbEGF domains are often connected by one or two amino acids to form larger, repetitive arrays, here referred to as 'cbEGF modules'.

Point mutations resulting in decreased affinity of factor IX to calcium are thought to be implicated in this bleeding disorder.

A similar problem occurs in patients with hemophilia B and carrying a mutation (Glu78Lys) in factor IX that prevents interaction of the two cbEGF modules with one another.

[24] Thus, domain-domain interactions (partially facilitated by calcium coordination) are crucial for the catalytic activity of proteins involved in the blood-clotting cascade.