Contents

Search

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

Function: 1) adhesive glycoproteins - reversible binding to the surfaces of cells, collagen, fibrin, heparin, DNA, actin 2) cell adhesion 3) cell motility 4) opsonization 5) wound healing 6) maintenance of cell shape 7) component of the blood-brain barrier (very small amounts in healthy people) 8) interaction with TNR mediates inhibition of cell adhesion & neurite outgrowth 9) 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* [9] - vascular deposition of FN1 is related to the pathogenicity of APOE(epsilon)4 [9] * a loss-of function variant of the fibronectin gene appears to prevent buildup of fibronectin in the blood-brain barrier [9] Comparative biology: - null mutation is lethal during embryogenesis in mice [6] Notes: - from the Latin fibra (fiber) & necter (to bind or connect

Interactions

molecular events

Related

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

General

blood protein cell adhesion protein globulin glycoprotein matrix protein oligomerizing protein

Properties

CONFIGURATION: dimer SIZE: MW = 250 kD MW = 440-500 kD entity length = 2386 aa COMPARTMENT: plasma membrane blood MOTIF: signal sequence {1-31} fibronectin type I domain or F1 module {50-90} binding site SITE: 52-272 FOR-BINDING-OF: fibrin heparan sulfate MOTIF: cysteine residue {C52} MODIFICATION: cysteine residue {C78} cysteine residue {C76} MODIFICATION: cysteine residue {C87} cysteine residue {C78} MODIFICATION: cysteine residue {C52} cysteine residue {C87} MODIFICATION: cysteine residue {C76} fibronectin type I domain or F1 module {95-228} (3) fibronectin type I domain or F1 module {229-345} MOTIF: cysteine residue {C231} MODIFICATION: cysteine residue {C260} cysteine residue {C258} MODIFICATION: cysteine residue {C270} cysteine residue {C260} MODIFICATION: cysteine residue {C231} cysteine residue {C270} MODIFICATION: cysteine residue {C258} fibronectin type I domain or F1 module {306-345} binding site SITE: 308-608 FOR-BINDING-OF: collagen MOTIF: cysteine residue {C308} MODIFICATION: cysteine residue {C335} cysteine residue {C333} MODIFICATION: cysteine residue {C342} cysteine residue {C335} MODIFICATION: cysteine residue {C308} cysteine residue {C342} MODIFICATION: cysteine residue {C333} fibronectin type II domain or F2 module (2) SITE: 355-403 FOR-BINDING-OF: collagen MOTIF: cysteine residue {*1} MODIFICATION: cysteine residue {*3} cysteine residue {*2} MODIFICATION: cysteine residue {*4} cysteine residue {*3} MODIFICATION: cysteine residue {*1} cysteine residue {*4} MODIFICATION: cysteine residue {*2} N-glycosylation site {N430} (3) fibronectin type I domain or F1 module {468-558} (3) fibronectin type III domain or F3 module {607-898} (3) DNA-binding motif SITE: 907-1172 MOTIF: fibronectin type III domain or F3 module {908-1172} (3) fibronectin type III domain or F3 module {1173-1265} MOTIF: N-glycosylation site {N1244} fibronectin type III domain or F3 module {1266-1720} (5) MOTIF: RGD cell-attachment sequence SITE: 1533-1536 FOR-BINDING-OF: integrin binding site SITE: 1721-1991 FOR-BINDING-OF: heparan sulfate MOTIF: fibronectin type III domain or F3 module {1723-1991} (3) Thr glycosylation site {T2064} (2) fibronectin type III domain or F3 module {2100-2190} MOTIF: N-glycosylation site {N2108} fibronectin type I domain or F1 module {2204-2248} binding site SITE: 2206-2337 FOR-BINDING-OF: fibrin MOTIF: cysteine residue {C2206} MODIFICATION: cysteine residue {C2235} cysteine residue {C2233} MODIFICATION: cysteine residue {C2245} cysteine residue {C2235} MODIFICATION: cysteine residue {C2206} cysteine residue {C2245} MODIFICATION: cysteine residue {C2233} fibronectin type I domain or F1 module {2249-2336} (2) cysteine residue {C2367} MODIFICATION: cysteine residue {C2371} cysteine residue {C2371} MODIFICATION: cysteine residue {C2367} Ser phosphorylation site {S2384} SECRETED-BY: endothelial cell macrophage synovial cell hepatocyte

Database Correlations

OMIM correlations UniProt P02751 PFAM correlations Entrez Gene 2335 Kegg hsa:2335

References

  1. Baron M, Norman DG, Campbell ID. Protein modules. Trends Biochem Sci. 1991 Jan;16(1):13-7. Review. PMID: 2053133
  2. Stryer Biochemistry WH Freeman & Co, New York, 1988 pg 277
  3. Clinical Guide to Laboratory Tests, 3rd edition, NW Tietz ed, WB Saunders, Philadelphia, 1995
  4. Peters JH, Carsons S, Yoshida M, Ko F, McDougall S, Loredo GA, Hahn TJ. Electrophoretic characterization of species of fibronectin bearing sequences from the N-terminal heparin-binding domain in synovial fluid samples from patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2003;5(6):R329-39. Epub 2003 Sep 8. PMID: 14680507
  5. Castelletti F et al. Mutations in FN1 cause glomerulopathy with fibronectin deposits. Proc Natl Acad Sci USA 2008;105:2538-2543 PMID: 18268355
  6. White ES, Baralle FE, Muro AF. New insights into form and function of fibronectin splice variants. J Pathol. 2008 Sep;216(1):1-14. Review. PMID: 18680111
  7. Wikipedia - fibronectin entry http://en.wikipedia.org/wiki/fibronectin
  8. UniProt :accession P02751
  9. Bhattarai P, Gunasekaran TI, Belloy ME et al Rare genetic variation in fibronectin 1 (FN1) protects against APOE(epsilon)4 in Alzheimer's disease. Acta Neuropathol. 2024 Apr 10;147(1):70. PMID: 38598053

Component-of

molecular complex