fibronectin; FN; cold-insoluble globulin; CIG; contains: anastellin; Ugl-Y1; Ugl-Y2; Ugl-Y3 (FN1, FN)

Function

• adhesive glycoproteins
  • reversible binding to the surfaces of cells, collagen, fibrin, heparin, DNA, actin
• cell adhesion
• cell motility
• opsonization
• wound healing
• maintenance of cell shape
• component of the blood-brain barrier (very small amounts in healthy people)
• interaction with TNR mediates inhibition of cell adhesion & neurite outgrowth
• interacts with FBLN1, AMBP, TNR, LGALS3BP

Structure

• length: 60 nm, width: 2.5 nm
• contains 12 fibronectin type-1 domains
• contains 2 fibronectin type-2 domains
• contains 16 fibronectin F3 modules
• fibrin-binding domain of fibronectin facilitates cross- linking of fibrin to fibronectin catalyzed by coagulation factor XIII
• fibroblasts & other cells that repair the site of injury adhere to the clot by interacting with the cell-binding region of fibronectin in the clot.
• collagen-binding domain of fibronectin in connection with the cell surface adhesion site (binding site for fibronectin receptor) facilitates adherance of cells to collagen; both bindings are reversible facilitating movement of cells on collagen sufaces
• heparan sulfate-binding site of fibronectin in connection with the cell surface adhesion site (binding site for fibronectin receptor) facilitates adherance of cells to proteoglycans
• H2N-Fibrin-Collagen-E3B-RGD-E3A-V-Fibrin-COOH

Compartment

secreted, extracellular matrix

Alternative splicing

• named isoforms=15
• additional isoforms seem to exist

Expression

• plasma fibronectin (soluble dimeric form) is secreted by hepatocytes; when present in plasma are called cold insoluble globulins.
• cellular fibronectin (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial & other cell types, is deposited as fibrils in the extracellular matrix
• Ugl-Y1, Ugl-Y2 & Ugl-Y3 are found in urine (0-17 years of age)

Pathology

• fibronectin is lost or reduced when cells undergo viral or chemical transformation
• highly susceptible to proteolysis
• fibronectins accumulate in insoluble form in cartilage & insoluble form in synovial fluid in rheumatoid & osteoarthritis
• mutations in FN1 cause glomerulopathy with fibronectin deposits
• excess fibronectin may be present in the blood-brain barrier of patients with Alzheimer's disease*
  • vascular deposition of FN1 is related to the pathogenicity of APOE(epsilon)4

* a loss-of function variant of the fibronectin gene appears to prevent buildup of fibronectin in the blood-brain barrier

Comparative biology

• null mutation is lethal during embryogenesis in mice

Notes

• from the Latin fibra (fiber) & necter (to bind or connect

More general terms

• glycoprotein
• blood protein
• cell adhesion protein
• globulin
• matrix protein
• oligomerizing protein

Additional terms

• CD49 or Very Late Antigen (VLA)
• fetal fibronectin in cervical-vaginal fluid
• glycoprotein IIB/IIIA
• scavenger receptor

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2335
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:2335
• OMIM: https://mirror.omim.org/entry/135600
• OMIM: https://mirror.omim.org/entry/601894
• UniProt: http://www.uniprot.org/uniprot/P02751.html