fibrillin3

Fibrillin-3 (FBN3) is a member of the fibrillin family of extracellular matrix glycoproteins. Like its relatives FBN1 and FBN2, fibrillin-3 is predicted to contribute to the formation and integrity of microfibrils, which are thread-like structures that support elastic fibers in connective tissues and help regulate signaling molecules such as transforming growth factor beta (TGF-β).

Structure: Fibrillin proteins are large secreted proteins characterized by a series of calcium-binding EGF-like domains and unique domains such as TB (transforming growth factor beta binding) domains. FBN3 shares this general domain organization and sequence similarity with other fibrillins, but it shows distinct tissue distribution and functional properties. The protein is secreted into the extracellular matrix where it assembles into microfibrils, often in concert with other ECM components.

Expression and regulation: FBN3 transcripts have been detected in several human tissues, with expression patterns reported to vary during development and in specific cell types. The regulatory elements controlling FBN3 expression are not as well characterized as those for FBN1 and FBN2.

Function: Through its incorporation into microfibrils, fibrillin-3 is thought to contribute to matrix assembly and to modulate the bioavailability of growth factors sequestered in the extracellular matrix, including TGF-β and possibly BMPs. Its precise interactions with other ECM proteins and its role in elastic fiber physiology are active areas of study.

Clinical relevance: Compared with FBN1 and FBN2, FBN3 mutations are not clearly associated with a defined heritable disorder. Rare variants have been reported, but robust genotype-phenotype correlations have not been established. Ongoing research explores whether FBN3 contributes to connective tissue biology or to disease in ways that are subtler or tissue-specific.

Research status: FBN3 remains less characterized than other fibrillins; model organisms and high-throughput expression studies are used to elucidate its functions and interactions.