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Gene Review

FN1  -  fibronectin 1

Homo sapiens

Synonyms: CIG, Cold-insoluble globulin, ED-B, FINC, FN, ...
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Disease relevance of FN1


Psychiatry related information on FN1


High impact information on FN1


Chemical compound and disease context of FN1


Biological context of FN1


Anatomical context of FN1

  • An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors [1].
  • Finally, extracellular fibronectin matrix assembly by VHL-/- mouse embryos and mouse embryo fibroblasts (MEFs), unlike their VHL+/+ counterparts, was grossly impaired [26].
  • In contrast with the activating CD29 mAb 8A2, a combination of blocking CD49 mAbs or the nonactivating but blocking CD29 mAb AIIB2 failed to inhibit completely eosinophil migration over FN-preincubated or HUVEC-covered filters. mAb 8A2 stimulated binding to FN but not to HUVEC [27].
  • Our studies identify a novel VLA4 and VLA5/FN-mediated pathway likely to be involved in regulating cell traffic between the cortex and medulla of the thymus [23].
  • Incubating monocytes with postreperfusion cardiac lymph that contained these FN fragments selectively reduced expression of VLA-5, an effect suppressed by specific immunoadsorption of the fragments [4].

Associations of FN1 with chemical compounds


Physical interactions of FN1

  • With the use of immunoprecipitation, it was found that CD95L binds directly to fibronectin [32].
  • Human epidermal keratinocytes obtained from normal skin attached and spread on thrombospondin (TSP)-coated plastic dishes but failed to attach and spread on untreated plastic culture dishes or dishes coated with fibronectin or laminin [33].
  • This pathway may represent a general mechanism, since PAI-1 also can detach cells from fibronectin and type-1 collagen [34].
  • For example, an antibody to the beta 1 subfamily of integrins partially inhibited binding of cells to intact CT but did not inhibit cell binding to the third FN type III repeat [35].
  • During S phase transit, adhesion to Fn was transiently increased while binding to VCAM-1 was reversibly decreased, after which adhesion to both ligands returned to baseline levels with cell cycle completion [36].

Enzymatic interactions of FN1

  • In situ degradation and cell adhesion assays showed that proteins produced from KLK8 splice variants modify the extracellular microenvironment by cleaving fibronectin [37].
  • Free hK2 was able to hydrolyze semenogelins and fibronectin in vitro [38].
  • Rather, PECAM-1 supports homophilic binding on HUVEC with similar characteristics to those we have previously reported for leukocytes and becomes tyrosine phosphorylated after homophilic PECAM-1 and integrin/fibronectin engagement [39].
  • Here we report that a specific octapeptide, SRNRCNDQ-NH2, consisting of residues 196-203 of the fibronectin molecule is a potent stimulator of t-PA-catalyzed plasminogen activation, resulting in a 15-fold increase in the kcat/Km of the activation reaction [40].
  • Comparison by two-dimensional phosphopeptide analyses indicated that the major sites of tyrosine and serine phosphorylation detected in the assays in vitro co-migrate with phosphopeptides derived from paxillin phosphorylated in vivo in response to plating cells on fibronectin [41].

Co-localisations of FN1


Regulatory relationships of FN1


Other interactions of FN1

  • In contrast to the extensive platelet spreading observed on fibronectin at all shear rates, platelet spreading on thrombospondin occurred only sporadically and at high shear rates [51].
  • MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin [52].
  • The shape of receptor clusters was slightly different and a colocalization of the two receptors was found when ECs were cultured on a mixed matrix of fn plus vn [53].
  • Disruption of uPAR-alpha5beta1 complexes in uPAR-rich cells with antibodies or a peptide that disrupts uPAR-beta1 interactions, reduced the FN-dependent ERK1/2 activation [54].
  • IGFBP-5 was found to bind to types III and IV collagen, laminin, and fibronectin [55].
  • Knockdown of perlecan expression by small interference RNA significantly abrogated the inhibitory effect of NK4 on fibronectin assembly and cell spreading [56].

Analytical, diagnostic and therapeutic context of FN1


  1. Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors. Prasad, M.L., Pellegata, N.S., Huang, Y., Nagaraja, H.N., de la Chapelle, A., Kloos, R.T. Mod. Pathol. (2005) [Pubmed]
  2. Differentially expressed genes in neurofibromatosis 1-associated neurofibromas and malignant peripheral nerve sheath tumors. Holtkamp, N., Mautner, V.F., Friedrich, R.E., Harder, A., Hartmann, C., Theallier-Janko, A., Hoffmann, K.T., von Deimling, A. Acta Neuropathol. (2004) [Pubmed]
  3. Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye. Connor, T.B., Roberts, A.B., Sporn, M.B., Danielpour, D., Dart, L.L., Michels, R.G., de Bustros, S., Enger, C., Kato, H., Lansing, M. J. Clin. Invest. (1989) [Pubmed]
  4. Fibronectin fragments modulate monocyte VLA-5 expression and monocyte migration. Trial, J., Baughn, R.E., Wygant, J.N., McIntyre, B.W., Birdsall, H.H., Youker, K.A., Evans, A., Entman, M.L., Rossen, R.D. J. Clin. Invest. (1999) [Pubmed]
  5. Inhibition of fibronectin binding and fibronectin-mediated cell adhesion to collagen by a peptide from the second type I repeat of thrombospondin. Sipes, J.M., Guo, N., Nègre, E., Vogel, T., Krutzsch, H.C., Roberts, D.D. J. Cell Biol. (1993) [Pubmed]
  6. Increased fibronectin expression in lung in the setting of chronic alcohol abuse. Burnham, E.L., Moss, M., Ritzenthaler, J.D., Roman, J. Alcohol. Clin. Exp. Res. (2007) [Pubmed]
  7. Evidence that autologous idiotypic regulation of anti-arginine-glycine-aspartic acid autoantibodies may influence development and progression of syphilitic lesions in infected rabbits. Baughn, R.E., Musher, D.M. Infect. Immun. (1992) [Pubmed]
  8. The preterm prediction study: patterns of cervicovaginal fetal fibronectin as predictors of spontaneous preterm delivery. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Goldenberg, R.L., Mercer, B.M., Iams, J.D., Moawad, A.H., Meis, P.J., Das, A., McNellis, D., Miodovnik, M., Menard, M.K., Caritis, S.N., Thurnau, G.R., Bottoms, S.F. Am. J. Obstet. Gynecol. (1997) [Pubmed]
  9. Fibronectin staining detects micro-organisms in aged and Alzheimer's disease brain. Howard, J., Pilkington, G.J. Neuroreport (1992) [Pubmed]
  10. Appearance of localized immunoreactivity for the alpha 4 integrin subunit and for fibronectin in brains from Alzheimer's, Lewy body dementia patients and aged controls. Van Gool, D., Carmeliet, G., Triau, E., Cassiman, J.J., Dom, R. Neurosci. Lett. (1994) [Pubmed]
  11. The molecular structure of cell adhesion molecules. Chothia, C., Jones, E.Y. Annu. Rev. Biochem. (1997) [Pubmed]
  12. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Jan, Y., Matter, M., Pai, J.T., Chen, Y.L., Pilch, J., Komatsu, M., Ong, E., Fukuda, M., Ruoslahti, E. Cell (2004) [Pubmed]
  13. Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Martignetti, J.A., Aqeel, A.A., Sewairi, W.A., Boumah, C.E., Kambouris, M., Mayouf, S.A., Sheth, K.V., Eid, W.A., Dowling, O., Harris, J., Glucksman, M.J., Bahabri, S., Meyer, B.F., Desnick, R.J. Nat. Genet. (2001) [Pubmed]
  14. Integrin activation by R-ras. Zhang, Z., Vuori, K., Wang, H., Reed, J.C., Ruoslahti, E. Cell (1996) [Pubmed]
  15. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Hughes, J., Ward, C.J., Peral, B., Aspinwall, R., Clark, K., San Millán, J.L., Gamble, V., Harris, P.C. Nat. Genet. (1995) [Pubmed]
  16. Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells. Pöllänen, J., Saksela, O., Salonen, E.M., Andreasen, P., Nielsen, L., Danø, K., Vaheri, A. J. Cell Biol. (1987) [Pubmed]
  17. Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Sanz-Rodríguez, F., Hidalgo, A., Teixidó, J. Blood (2001) [Pubmed]
  18. Retinoic acid increases tyrosine phosphorylation of focal adhesion kinase and paxillin in MCF-7 human breast cancer cells. Zhu, W.Y., Jones, C.S., Amin, S., Matsukuma, K., Haque, M., Vuligonda, V., Chandraratna, R.A., De Luca, L.M. Cancer Res. (1999) [Pubmed]
  19. Fibronectin Increases Matrix Metalloproteinase 9 Expression through Activation of c-Fos via Extracellular-regulated Kinase and Phosphatidylinositol 3-Kinase Pathways in Human Lung Carcinoma Cells. Han, S., Ritzenthaler, J.D., Sitaraman, S.V., Roman, J. J. Biol. Chem. (2006) [Pubmed]
  20. Matriptase-2, a membrane-bound mosaic serine proteinase predominantly expressed in human liver and showing degrading activity against extracellular matrix proteins. Velasco, G., Cal, S., Quesada, V., Sánchez, L.M., López-Otín, C. J. Biol. Chem. (2002) [Pubmed]
  21. A genetic map of nine loci on bovine chromosome 2. Beever, J.E., Da, Y., Ron, M., Lewin, H.A. Mamm. Genome (1994) [Pubmed]
  22. In situ hybridization applied to Waardenburg syndrome. Wu, B.L., Milunsky, A., Wyandt, H., Hoth, C., Baldwin, C., Skare, J. Cytogenet. Cell Genet. (1993) [Pubmed]
  23. Cell adhesion and migration are regulated at distinct stages of thymic T cell development: the roles of fibronectin, VLA4, and VLA5. Crisa, L., Cirulli, V., Ellisman, M.H., Ishii, J.K., Elices, M.J., Salomon, D.R. J. Exp. Med. (1996) [Pubmed]
  24. T cell receptor- and beta 1 integrin-mediated signals synergize to induce tyrosine phosphorylation of focal adhesion kinase (pp125FAK) in human T cells. Maguire, J.E., Danahey, K.M., Burkly, L.C., van Seventer, G.A. J. Exp. Med. (1995) [Pubmed]
  25. Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins. Lévesque, J.P., Leavesley, D.I., Niutta, S., Vadas, M., Simmons, P.J. J. Exp. Med. (1995) [Pubmed]
  26. The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Ohh, M., Yauch, R.L., Lonergan, K.M., Whaley, J.M., Stemmer-Rachamimov, A.O., Louis, D.N., Gavin, B.J., Kley, N., Kaelin, W.G., Iliopoulos, O. Mol. Cell (1998) [Pubmed]
  27. Freezing adhesion molecules in a state of high-avidity binding blocks eosinophil migration. Kuijpers, T.W., Mul, E.P., Blom, M., Kovach, N.L., Gaeta, F.C., Tollefson, V., Elices, M.J., Harlan, J.M. J. Exp. Med. (1993) [Pubmed]
  28. Thrombospondin binds to monocytes-macrophages and mediates platelet-monocyte adhesion. Silverstein, R.L., Nachman, R.L. J. Clin. Invest. (1987) [Pubmed]
  29. VLA-5 is expressed by mouse and human long-term repopulating hematopoietic cells and mediates adhesion to extracellular matrix protein fibronectin. van der Loo, J.C., Xiao, X., McMillin, D., Hashino, K., Kato, I., Williams, D.A. J. Clin. Invest. (1998) [Pubmed]
  30. Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. Lawler, J., Weinstein, R., Hynes, R.O. J. Cell Biol. (1988) [Pubmed]
  31. Caveolin-1-dependent beta1 integrin endocytosis is a critical regulator of fibronectin turnover. Shi, F., Sottile, J. J. Cell. Sci. (2008) [Pubmed]
  32. Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity. Aoki, K., Kurooka, M., Chen, J.J., Petryniak, J., Nabel, E.G., Nabel, G.J. Nat. Immunol. (2001) [Pubmed]
  33. Thrombospondin-induced adhesion of human keratinocytes. Varani, J., Nickoloff, B.J., Riser, B.L., Mitra, R.S., O'Rourke, K., Dixit, V.M. J. Clin. Invest. (1988) [Pubmed]
  34. Plasminogen activator inhibitor-1 detaches cells from extracellular matrices by inactivating integrins. Czekay, R.P., Aertgeerts, K., Curriden, S.A., Loskutoff, D.J. J. Cell Biol. (2003) [Pubmed]
  35. Multiple integrins mediate cell attachment to cytotactin/tenascin. Prieto, A.L., Edelman, G.M., Crossin, K.L. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  36. Adhesion of synchronized human hematopoietic progenitor cells to fibronectin and vascular cell adhesion molecule-1 fluctuates reversibly during cell cycle transit in ex vivo culture. Huygen, S., Giet, O., Artisien, V., Di Stefano, I., Beguin, Y., Gothot, A. Blood (2002) [Pubmed]
  37. Human kallikrein 8 protease confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness. Sher, Y.P., Chou, C.C., Chou, R.H., Wu, H.M., Wayne Chang, W.S., Chen, C.H., Yang, P.C., Wu, C.W., Yu, C.L., Peck, K. Cancer Res. (2006) [Pubmed]
  38. Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesicle proteins after ejaculation. Deperthes, D., Frenette, G., Brillard-Bourdet, M., Bourgeois, L., Gauthier, F., Tremblay, R.R., Dubé, J.Y. J. Androl. (1996) [Pubmed]
  39. Homophilic PECAM-1(CD31) interactions prevent endothelial cell apoptosis but do not support cell spreading or migration. Bird, I.N., Taylor, V., Newton, J.P., Spragg, J.H., Simmons, D.L., Salmon, M., Buckley, C.D. J. Cell. Sci. (1999) [Pubmed]
  40. Modulation of tissue plasminogen activator-catalyzed plasminogen activation by synthetic peptides derived from the amino-terminal heparin binding domain of fibronectin. Stack, M.S., Pizzo, S.V. J. Biol. Chem. (1993) [Pubmed]
  41. Adhesion of fibroblasts to fibronectin stimulates both serine and tyrosine phosphorylation of paxillin. Bellis, S.L., Perrotta, J.A., Curtis, M.S., Turner, C.E. Biochem. J. (1997) [Pubmed]
  42. Latent transforming growth factor-beta 1 and its binding protein are components of extracellular matrix microfibrils. Taipale, J., Saharinen, J., Hedman, K., Keski-Oja, J. J. Histochem. Cytochem. (1996) [Pubmed]
  43. Biological functions of entactin. Chung, A.E., Dong, L.J., Wu, C., Durkin, M.E. Kidney Int. (1993) [Pubmed]
  44. The receptor for urokinase-type plasminogen activator regulates fibronectin matrix assembly in human skin fibroblasts. Monaghan, E., Gueorguiev, V., Wilkins-Port, C., McKeown-Longo, P.J. J. Biol. Chem. (2004) [Pubmed]
  45. Localization of fibronectin matrix assembly sites on fibroblasts and endothelial cells. Christopher, R.A., Kowalczyk, A.P., McKeown-Longo, P.J. J. Cell. Sci. (1997) [Pubmed]
  46. Interaction of alphaPIX (ARHGEF6) with beta-parvin (PARVB) suggests an involvement of alphaPIX in integrin-mediated signaling. Rosenberger, G., Jantke, I., Gal, A., Kutsche, K. Hum. Mol. Genet. (2003) [Pubmed]
  47. TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. Hocevar, B.A., Brown, T.L., Howe, P.H. EMBO J. (1999) [Pubmed]
  48. Fibronectin matrix regulates activation of RHO and CDC42 GTPases and cell cycle progression. Bourdoulous, S., Orend, G., MacKenna, D.A., Pasqualini, R., Ruoslahti, E. J. Cell Biol. (1998) [Pubmed]
  49. Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways. Esparza, J., Vilardell, C., Calvo, J., Juan, M., Vives, J., Urbano-Márquez, A., Yagüe, J., Cid, M.C. Blood (1999) [Pubmed]
  50. Conformational regulation of the fibronectin binding and alpha 3beta 1 integrin-mediated adhesive activities of thrombospondin-1. Rodrigues, R.G., Guo , N., Zhou, L., Sipes, J.M., Williams, S.B., Templeton, N.S., Gralnick, H.R., Roberts, D.D. J. Biol. Chem. (2001) [Pubmed]
  51. Thrombospondin-platelet interactions. Role of divalent cations, wall shear rate, and platelet membrane glycoproteins. Agbanyo, F.R., Sixma, J.J., de Groot, P.G., Languino, L.R., Plow, E.F. J. Clin. Invest. (1993) [Pubmed]
  52. Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production. Azzam, H.S., Arand, G., Lippman, M.E., Thompson, E.W. J. Natl. Cancer Inst. (1993) [Pubmed]
  53. Fibronectin and vitronectin regulate the organization of their respective Arg-Gly-Asp adhesion receptors in cultured human endothelial cells. Dejana, E., Colella, S., Conforti, G., Abbadini, M., Gaboli, M., Marchisio, P.C. J. Cell Biol. (1988) [Pubmed]
  54. Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. Aguirre Ghiso, J.A., Kovalski, K., Ossowski, L. J. Cell Biol. (1999) [Pubmed]
  55. Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I. Jones, J.I., Gockerman, A., Busby, W.H., Camacho-Hubner, C., Clemmons, D.R. J. Cell Biol. (1993) [Pubmed]
  56. Angioinhibitory action of NK4 involves impaired extracellular assembly of fibronectin mediated by perlecan-NK4 association. Sakai, K., Nakamura, T., Matsumoto, K., Nakamura, T. J. Biol. Chem. (2009) [Pubmed]
  57. Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering. Rüegg, C., Postigo, A.A., Sikorski, E.E., Butcher, E.C., Pytela, R., Erle, D.J. J. Cell Biol. (1992) [Pubmed]
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