FKBP5

Fibulin-5
Identifiers
Symbol	?
NCBI gene	10516
HGNC	3607
OMIM	604580
RefSeq	NM_006329
UniProt	Q9UBX5
Search for Structures Swiss-model Domains InterPro

Fibulin-5 (FBLN5) is a protein encoded by the FBLN5 gene in humans. It is a member of the fibulin family of proteins, which are extracellular matrix proteins involved in the stabilization of elastic fibers. Fibulin-5 plays a crucial role in the development and maintenance of elastic tissues, such as those found in the skin, lungs, and blood vessels.

Structure

Fibulin-5 is a secreted glycoprotein that consists of several domains, including an N-terminal signal peptide, a unique N-terminal domain, five calcium-binding epidermal growth factor (EGF)-like domains, and a C-terminal fibulin-type module. The EGF-like domains are important for calcium binding, which is essential for the protein's structural integrity and function.

Function

Fibulin-5 is primarily involved in the assembly and organization of elastic fibers. It interacts with other extracellular matrix proteins such as elastin, fibrillin, and lysyl oxidase-like 1 (LOXL1) to facilitate the cross-linking and deposition of elastin fibers. This process is critical for the elasticity and resilience of tissues that undergo repetitive stretching and relaxation.

Fibulin-5 also plays a role in cell adhesion and migration, influencing processes such as wound healing and tissue repair. It has been shown to interact with integrins, which are cell surface receptors that mediate cell-extracellular matrix interactions.

Clinical Significance

Mutations in the FBLN5 gene have been associated with several disorders, most notably cutis laxa, a connective tissue disorder characterized by loose, sagging skin and other systemic manifestations. The loss of fibulin-5 function leads to defects in elastic fiber formation, contributing to the clinical features of the disease.

Fibulin-5 has also been implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss in the elderly. Alterations in the expression or function of fibulin-5 may affect the integrity of Bruch's membrane and the choroidal vasculature, contributing to the development of AMD.

Research Directions

Ongoing research is focused on understanding the precise molecular mechanisms by which fibulin-5 regulates elastic fiber assembly and its interactions with other matrix proteins. There is also interest in exploring the potential therapeutic applications of fibulin-5 in regenerative medicine and tissue engineering, particularly in the context of diseases involving elastic fiber defects.

Also see

• Elastic fiber
• Extracellular matrix
• Cutis laxa
• Age-related macular degeneration
• Fibrillin