EGF-like domains

EGF-like domains were identified in extracellular proteins such as fibrillin-1. EGF-modules contain about 40-45 amino acids including six cysteine residues which normally build S-S disulfide bond bridges. Mutations in the fibrillin-1 gene cause Marfan syndrome and related disorders. 

EGF Epidermal growth factor (EGF)-like domain E(MFP) 0(0) 62(158) 1A3P... 

L-Asp hydroxylated at the /3-carbon to generate 7a ro-3-hydroxyl-L-aspartic acid has so far only been detected in cinnamycin and the duramycins, lantibiotics produced by actinomycetes. " This modification has also been found in mammalian proteins, such as the vitamin K-dependent protein C, and the epidermal growth factor (EGF)-like domain in human plasma factor IX. Both bovine and human aspartyl-/3-hydroxylases have been purified and characterized and their in vitro hydroxylation activity has been shown using proteins... 

EF hand domains, 46 442, 443-445 EGF-like domains, 46 471-479 extracellular, 46 442, 470-485 intracellular, 46 442, 443-456 ligand preferences, 46 442 binding sites, 42 113-114 biological coordination chemistry, 46 442 biological roles, 46 441-442 cation, nuclear properties, 27 11 complexes... 

Ca2+ which helps to tie these proteins to the phospholipids of platelet surfaces. In factors VII, IX, X, and protein C this Ca2+-binding domain is followed by two epidermal growth factor (EGF)-like domains, each containing one residue of en/Firo-P-hydroxyaspartate or hydroxyasparagine formed by hydroxylation of an aspartate or asparagine residue in the first EGF-like domain.540,540a,b The C-terminal catalytic domain of each enzyme contains the protease active site. 

Jacobsen NE, Abadi N, Sliwkowski MX, Reilly D, Skelton NJ, Fairbrother WJ. High resolution solution structure of the EGF-like domain of heregulin-a. Biochemistry 1996 35 3402-3417. 

The NRG1-ICD is essential for cell survival. Mice in which a stop codon was introduced immediately following the transmembrane domain die during mid-gestation with a phenotype indistinguishable from that of mice in which all NRG1 isoform expression has been disrupted (the EGF-like domain, or pan-Nrg knockouts) (Liu et al., 1998a). 

A large protein family that contains extracellular domains homologous to EGF is called the EGF-domain proteins. EGF-like domains or modules are often found in many extracellular and membrane proteins (>70). They are involved in blood coagulation, fibrinolysis and the complement systems, matrix proteins, cell surface receptors, the low-density hpoprotein receptor and the developmentally important receptor. Notch. EGF-like domains may exist as multiple copies within proteins such as in the Drosophila protein Notch with 36 copies or as a single copy as in EGF itself It can also be found in conjunction with other modules. 

A protein S, the cofactor of activated protein C, has four EGF-like modules in tandem. The stracture of N-terminal EGF modules is very similar to that of non-calcium-binding modules. Calcium binding only results in a limited local conformational change. The N-terminal loop is better defined and moves toward the major /3-sheet. The N-terminal non-catalytic Gla and EGF-like domains provide coagulation serine proteases with different calcium affinities for certain biological membranes, and also mediate protein-protein interactions. ... 

Selectins are cell-adhesion molecules that mediate leukocyte recruitment in irmnune reactions and signal transduction. Selectins comprise three members termed E-, P-, and L-selectin. The CRD is located at the N-terminus, followed by an EGF-hke domain. There are various numbers of consensus repeat sequences following the EGF-like domain. P-selectin, L-selectin and E-selectin contain nine, six, and two repeats, respectively. A transmembrane segment and a cytoplasmic tail are located at the C-terminal. The key domains for target recognition and sugar binding are the N-terminal CRD and EGF-like domain. ... 

Figure 26.20. Structure of Propeller Domaiu. The six-bladed propeller domain and an adjacent EGF-like domain of the LDL receptor.

Also see color figure.) Tissue factor-factor Vila complex. The three-dimensional structure of the complex of factor Vila and tissue factor (minus the transmembrane polypeptide domain of the tissue factor) in the absence of membrane surface. It is approximately 115 A in length and has a diameter of 40-50 A. Factor Vila shows its four distinct domains the Gla domain, two EGF-like domains, and the proteinase domain. Tissue factor contacts factor VHa via the interface between the two fibronectin type Ill-like domains. All four domains of factor Vila appear to be involved in the interaction between tissue factor and factor Vila. The Gla domain of factor Vila is folded very similarly to the Gla domain of prothrombin (Gla domain of prothrombin fragment 1). Activation of factor VII can be catalyzed by thrombin, factor Xa, factor Vila, and factor Xlla—all by cleavage at Arg -Ile . Secondary structures are shown in the center diagram two views of the close interactions between TF and factor Vila are shown in the two diagrams at each side. 

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