Fibulins: physiological and disease perspectives

Abstract

The fibulins are a family of proteins that are associated with basement membranes and elastic extracellular matrix fibres. This review summarizes findings from studies of animal models of fibulin deficiency, human fibulin gene mutations, human tumours and injury models that have advanced our understanding of the normal and pathological roles of members of this formerly obscure family.

Figure 1

Modular structures of the fibulins. The most recent addition to the family, fibulin 6 (hemicentin), was originally identified in the nematode (Vogel & Hedgecock, 2001), with orthologues in other species (human, mouse and rat) having now been identified. Nine of the 48 immunoglobulin domains in fibulin 6 are shown (double slashes indicate where the omitted domains occur). Alternative splice variants are known for fibulins 1–4, albeit only variants for fibulin 1 (designated A–D) are displayed.

Figure 2

Alignment of fibulin-type module sequences from the human fibulins. The carboxy-terminal regions of the fibulins were aligned using ClustalW 1.82, and Boxshade 3.21 was used to highlight conserved amino acids. Identical residues are indicated in the blue background and chemically similar residues with green shading. The GenBank accession numbers for the sequences depicted are as follows: fibulin 1C, ; fibulin 1D, ; fibulin 2, ; fibulin 3, ; fibulin 4, ; fibulin 5, ; fibulin 6, .