Fibulin
Encyclopedia
Fibulin (now known as Fibulin-1 FBLN1
) is the prototypic member of a multigene family, currently with seven members. Fibulin-1 is a calcium-binding glycoprotein. In vertebrates, fibulin-1 is found in blood
and extracellular matrices. In the extracellular matrix, fibulin-1 associates with basement membrane
s and elastic fibers. The association with these matrix structures is mediated by its ability to interact with numerous extracellular matrix constituents including fibronectin
, proteoglycan
s, laminin
s and tropoelastin
. In blood, fibulin-1 binds to fibrinogen
and incorporates into clots.
Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers. 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. The amino-terminal domain I of fibulin consists of three anaphylatoxin
-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilized by three disulphide bridges in the pattern Cys14, Cys25 and Cys36 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats.
FBLN1
FBLN1 is the gene encoding fibulin-1, an extracellular matrix and plasma protein.- Function :Fibulin-1 is a secreted glycoprotein that is found in association with extracellular matrix structures including fibronectin-containing fibers, elastin-containing fibers and basement membranes...
) is the prototypic member of a multigene family, currently with seven members. Fibulin-1 is a calcium-binding glycoprotein. In vertebrates, fibulin-1 is found in blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
and extracellular matrices. In the extracellular matrix, fibulin-1 associates with basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
s and elastic fibers. The association with these matrix structures is mediated by its ability to interact with numerous extracellular matrix constituents including fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
, proteoglycan
Proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan chain. The point of attachment is a Ser residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge...
s, laminin
Laminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
s and tropoelastin
Tropoelastin
Tropoelastin is a water-soluble molecule with a molecular weight of approximately 72,000 daltons. Multiple tropoelastin molecules covalently bind together with crosslinks to form the protein elastin that is very prevalent in the body. There is only one gene for this molecule and so only one protein...
. In blood, fibulin-1 binds to fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
and incorporates into clots.
Fibulins are secreted glycoproteins that become incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers. 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. The amino-terminal domain I of fibulin consists of three anaphylatoxin
Anaphylatoxin
Anaphylatoxins, or anaphylotoxins, are fragments that are produced as part of the activation of the complement system.. Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense...
-like (AT) modules, each approximately 40 residues long and containing four or six cysteines. The structure of an AT module was determined for the complement-derived anaphylatoxin C3a, and was found to be a compact alpha-helical fold that is stabilized by three disulphide bridges in the pattern Cys14, Cys25 and Cys36 (where Cys is cysteine). The bulk of the remaining portion of the fibulin molecule is a series of nine EGF-like repeats.
Genes
- FBLN1FBLN1FBLN1 is the gene encoding fibulin-1, an extracellular matrix and plasma protein.- Function :Fibulin-1 is a secreted glycoprotein that is found in association with extracellular matrix structures including fibronectin-containing fibers, elastin-containing fibers and basement membranes...
, FBLN2FBLN2Fibulin-2 is a protein that in humans is encoded by the FBLN2 gene.-Interactions:FBLN2 has been shown to interact with Laminin, alpha 1, Laminin, alpha 5 and Perlecan.-Further reading:...
, FBLN3, FBLN4, FBLN5FBLN5Fibulin-5 is a protein that in humans is encoded by the FBLN5 gene.-Clinical relevance:FBLN5 mutations have been described in patients with age-related macular degeneration, as well as being involved in Charcot-Marie-Tooth neuropathies....
, FBLN7 and HMCN1HMCN1Hemicentin-1 is a protein that in humans is encoded by the HMCN1 gene.-Further reading:...
is also known as "fibulin-6".