Fibronectin

Fibronectin 1
PDB rendering based on 1e88.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1e88​, 1e8b​, 1fbr​, 1fna​, 1fnf​, 1fnh​, 1j8k​, 1o9a​, 1oww​, 1q38​, 1qgb​, 1qo6​, 1ttf​, 1ttg​, 2cg6​, 2cg7​, 2cku​, 2fn2​, 2fnb​, 2gee​, 2h41​, 2h45​, 2ha1​
Identifiers
Symbols	FN1 ; CIG; DKFZp686F10164; DKFZp686H0342; DKFZp686I1370; DKFZp686O13149; FINC; FN; LETS; MSF
External IDs	Template:OMIM5 Template:MGI HomoloGene: 1533
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Fibronectin is a high-molecular-weight glycoprotein containing about 5% carbohydrate that binds to membrane spanning receptor proteins called integrins. In addition to integrins, they also bind extracellular matrix components such as collagen, fibrin and heparan sulfate.

Fibronectin can be found in the blood plasma in its soluble form which is composed of two 250 kDa subunits joined together by disulfide bonds. Plasma fibronectin is made in the liver by hepatocytes. The insoluble form that was formerly called cold-insoluble globulin is a large complex of cross-linked subunits.

There are several isoforms of fibronectin all of which are the product of a single gene. The structure of these isoforms are made of three types of repeated internal regions called I, II and III which exhibit different lengths and presence or absence of disulfide bonds. Alternative splicing of the Pre-mRNA leads to the combination of these three types of regions but also to a variable region.

Fibronectin is involved in the wound healing process and so can be used as a therapeutic agent. It is also one of the few proteins for which production increases with age without any associated pathology. Fibronectin is also found in normal human saliva, which helps prevent colonization of the oral cavity and pharynx by potentially pathogenic bacteria.

Fibronectin and cancer

Fibronectin has been implicated in carcinoma development. In lung carcinoma, fibronectin expression is increased, especially in non–small cell lung carcinoma. The adhesion of lung carcinoma cells to fibronectin enhances tumorigenicity and confers resistance to apoptosis induced by standard chemotherapeutic agents. Fibronectin has been shown to stimulate the phosphatidylinositol 3-kinase (PI3K), which is capable of controlling the expression of cyclin D and related genes involved in cell cycle control. This suggests that fibronectin promotes lung tumor growth/survival and resistance to therapy and could represent a novel target for the development of new anticancer drugs.

Structure of fibronectin

Fibronectin is composed of two similar polypeptide chains of approximately 30 modules. These polypeptide chains are attached by disulfide bridges, and are folded into a linear series of 5 or 6 functional units. These functional units contain interaction sites for other Extracellular components or cell surface molecules.

Functions of fibronectin

Other than the ones stated previously, Fibronectin has numerous functions that ensure the normal functioning of life. One of its more notable functions is its role as a 'guide' in cellular migration pathways in mammalian development, particularly the Neural Crest (ectoderm cells that will develop into skin pigment cells as well as some bones of the skull). Fibronectin helps maintain the shape of cells by lining up and organizing intracellular cytoskeleton by means of receptors. It helps stabilize the attachment of ECM (Extracellular matrix) to cells by acting as binding sites for cell surface receptors. More generally though, Fibronectin helps create a cross-linked network within the Extracellular Matrix by having binding sites for other ECM components.

Further reading

• ffrench-Constant C (1996). "Alternative splicing of fibronectin--many different proteins but few different functions". Exp. Cell Res. 221 (2): 261–71. doi:10.1006/excr.1995.1374. PMID 7493623.
• Snásel J, Pichová I (1997). "The cleavage of host cell proteins by HIV-1 protease". Folia Biol. (Praha). 42 (5): 227–30. PMID 8997639.
• Schor SL, Schor AM (2003). "Phenotypic and genetic alterations in mammary stroma: implications for tumour progression". Breast Cancer Res. 3 (6): 373–9. PMID 11737888.
• Przybysz M, Katnik-Prastowska I (2002). "[Multifunction of fibronectin]". Postȩpy higieny i medycyny doświadczalnej. 55 (5): 699–713. PMID 11795204.
• Rameshwar P, Oh HS, Yook C; et al. (2003). "Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis". Acta Haematol. 109 (1): 1–10. PMID 12486316.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Cho J, Mosher DF (2006). "Role of fibronectin assembly in platelet thrombus formation". J. Thromb. Haemost. 4 (7): 1461–9. doi:10.1111/j.1538-7836.2006.01943.x. PMID 16839338.
• Schmidt DR, Kao WJ (2007). "The interrelated role of fibronectin and interleukin-1 in biomaterial-modulated macrophage function". Biomaterials. 28 (3): 371–82. doi:10.1016/j.biomaterials.2006.08.041. PMID 16978691.
• Dallas SL, Chen Q, Sivakumar P (2006). "Dynamics of assembly and reorganization of extracellular matrix proteins". Curr. Top. Dev. Biol. 75: 1–24. doi:10.1016/S0070-2153(06)75001-3. PMID 16984808.CS1 maint: Multiple names: authors list (link)

See also

• Fetal fibronectin
• Fibronectin type II domain

External links

• The Fibronectin Protein
• Fibronectin at the US National Library of Medicine Medical Subject Headings (MeSH)
• Fibronectin molecular interactions