Fibulins: a versatile family of extracellular matrix proteins

Key Points The fibulin protein family consists of five isoforms (fibulin-1, -2, -3, -4 and -5), which are localized to the extracellular matrix. Fibulin isoforms vary in size (50–200 kDa) and have an elongated multidomain structure that is dominated by numerous calcium-binding epidermal growth factor-like modules. The fibulins show a widespread deposition in various extracellular structures such as microfibrils, basement membranes and elastic fibres. The widespread distribution of fibulins correlates well with their broad binding repertoire for fibronectin, collagens, basement-membrane proteins, elastin and proteoglycans. The cell-biological activities of fibulins include the binding of integrin receptors and the modulation of cell proliferation and malignant transformation. New information on the biological roles of the fibulins is now becoming available from the analysis of inherited human diseases and transgenic animals. Fibulins are a newly recognized family of extracellular matrix proteins. The five known members of the family share an elongated structure and many calcium-binding sites, owing to the presence of tandem arrays of epidermal growth factor-like domains. They have overlapping binding sites for several basement-membrane proteins, tropoelastin, fibrillin, fibronectin and proteoglycans, and they participate in diverse supramolecular structures. New insights into their biological roles are now emerging from studies of transgenic mice and of some inherited human diseases.