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Gene Review

FYN  -  FYN proto-oncogene, Src family tyrosine...

Homo sapiens

Synonyms: MGC45350, Proto-oncogene Syn, Proto-oncogene c-Fyn, SLK, SYN, ...
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Disease relevance of FYN

  • Loss of a FYN-regulated differentiation and growth arrest pathway in advanced stage neuroblastoma [1].
  • Altered p59Fyn kinase expression accompanies disease progression in Alzheimer's disease: implications for its functional role [2].
  • Rabbit antisera raised against human FYN-specific peptides were used to evaluate the expression of the fyn gene product in normal and murine polyomavirus middle tumor antigen (MTAg)-transformed rat cells [3].
  • These include hepatitis B virus pre-S1, human SYN-kinase, rodent Gi alpha, and bovine transducin-alpha [4].
  • Expression of SLK mRNA and protein and kinase activity are increased during kidney development and recovery from ischemic acute renal failure [5].

High impact information on FYN

  • Similarly, chorionic gonadotropin kills KS SLK, cells from another neoplastic cell line (established from a non-HIV-associated KS), as well as the hyperplastic KS cells from clinical specimens grown in short-term culture, but does not kill normal endothelial cells [6].
  • Compared to CON, patients with SYN had blunted increases in MSNA at low tilt levels, followed by a progressive decrease and ultimately complete disappearance of MSNA with syncope [7].
  • SYN patients also had attenuation of norepinephrine increases and lower baroreflex slope sensitivity, both during tilt and after pharmacologic testing [7].
  • Fc gamma RIIA-mediated signal transduction was defective in a transfected mutant T-cell line exhibiting reduced expression of the tyrosine kinases LCK and FYN [8].
  • Acquisition of transforming properties by FYN, a normal SRC-related human gene [9].

Chemical compound and disease context of FYN


Biological context of FYN


Anatomical context of FYN

  • However, in this report, we now demonstrate that neither LCK nor FYN are obligatory for IL-2-induced growth of HTLV-I-infected human T cells [12].
  • We recently described another member of this family, designated FYN, whose cDNA was isolated from normal human fibroblasts [9].
  • To examine the possible role of FYN as an oncogene, we investigated the effects of FYN overexpression on NIH 3T3 cells [9].
  • These results indicate that the induction of germ-line C epsilon transcripts in IL-4-stimulated DND39 cells is essentially dependent on the activation of tyrosine kinase, possibly FYN kinase [15].
  • Cleavage occurs in the N-terminal domain of p59Fyn between Asp19 and Gly20 and is accompanied by relocation of an active p57Fyn kinase to cytoplasm of Fas-stimulated Jurkat cells as judged by both biochemical and confocal microscopy experiments [14].

Associations of FYN with chemical compounds

  • A mechanism for the inhibition of TCR signaling by nocodazole was suggested by in vitro assays, which revealed that the drug inhibited the kinase activity of LCK and, to a lesser extent, FYN [16].
  • Here we report the presence in human sperm of alpha7, alpha9, alpha3, alpha5, and beta4 nicotinic acetylcholine receptor subunits and the following proteins known to be associated with the receptor in the somatic cell: rapsyn and the tyrosine kinases c-SRC and FYN [17].
  • Furthermore, this phosphotyrosine was essential for coimmunoprecipitation of FYN with mSKAP55R [18].
  • The 3'-untranslated region (3'-UTR) of SLK mRNA contains multiple adenine and uridine-rich elements, suggesting that 3'-UTR may regulate mRNA stability [5].
  • The structures obtained show a trans-syn cyclobutane linkage and the glycosidic angles are SYN and ANTI for thymidine and deoxyadenosine, respectively [19].

Physical interactions of FYN

  • Short-term GC treatment induces dissociation of this protein complex, resulting in impaired TCR signalling as a consequence of abrogated LCK/FYN activation [20].

Enzymatic interactions of FYN

  • The MTAg molecules immunoprecipitated by FYN antisera were phosphorylated on tyrosine during immune-complex kinase reactions at sites similar to those found on MTAg in complexes with pp60c-src [3].

Regulatory relationships of FYN

  • IL-6 induced the activation and tyrosine phosphorylation of p59Fyn, p56/59Hck, and p56Lyn [21].
  • TLX is predominately expressed in the brain and maps to RMD-2 at 6q21 between DNA markers FYN and D6S447, in a YAC clone that also contains marker D6S246 [22].

Other interactions of FYN

  • Lack of expression of LCK or FYN in the HTLV-I-infected T cell lines was demonstrated by a combination of Northern blotting, polymerase chain reaction, Western blotting, and in vitro kinase activity [12].
  • Coprecipitation experiments with anti-Hck, anti-Lyn, anti-Fyn, and anti-gp130 antibodies revealed a physical association with gp130 of p56/59Hck and p56Lyn, but not p59Fyn, in LP-1 cells [21].
  • RESULTS: The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually [23].
  • SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55 [24].
  • The SH2(CHK) binding to the two sites is direct and not through phosphorylated intermediates such as FYN or SHC [25].

Analytical, diagnostic and therapeutic context of FYN


  1. Loss of a FYN-regulated differentiation and growth arrest pathway in advanced stage neuroblastoma. Berwanger, B., Hartmann, O., Bergmann, E., Bernard, S., Nielsen, D., Krause, M., Kartal, A., Flynn, D., Wiedemeyer, R., Schwab, M., Schäfer, H., Christiansen, H., Eilers, M. Cancer Cell (2002) [Pubmed]
  2. Altered p59Fyn kinase expression accompanies disease progression in Alzheimer's disease: implications for its functional role. Ho, G.J., Hashimoto, M., Adame, A., Izu, M., Alford, M.F., Thal, L.J., Hansen, L.A., Masliah, E. Neurobiol. Aging (2005) [Pubmed]
  3. Association of p60fyn with middle tumor antigen in murine polyomavirus-transformed rat cells. Horak, I.D., Kawakami, T., Gregory, F., Robbins, K.C., Bolen, J.B. J. Virol. (1989) [Pubmed]
  4. Myristoyl CoA:protein N-myristoyltransferase activities from rat liver and yeast possess overlapping yet distinct peptide substrate specificities. Towler, D.A., Adams, S.P., Eubanks, S.R., Towery, D.S., Jackson-Machelski, E., Glaser, L., Gordon, J.I. J. Biol. Chem. (1988) [Pubmed]
  5. The 3'-untranslated region of the Ste20-like kinase SLK regulates SLK expression. Cybulsky, A.V., Takano, T., Papillon, J., Hao, W., Mancini, A., Di Battista, J.A., Cybulsky, M.I. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  6. Tumorigenesis and metastasis of neoplastic Kaposi's sarcoma cell line in immunodeficient mice blocked by a human pregnancy hormone. Lunardi-Iskandar, Y., Bryant, J.L., Zeman, R.A., Lam, V.H., Samaniego, F., Besnier, J.M., Hermans, P., Thierry, A.R., Gill, P., Gallo, R.C. Nature (1995) [Pubmed]
  7. Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt. Mosqueda-Garcia, R., Furlan, R., Fernandez-Violante, R., Desai, T., Snell, M., Jarai, Z., Ananthram, V., Robertson, R.M., Robertson, D. J. Clin. Invest. (1997) [Pubmed]
  8. Transfection of an Fc gamma receptor cDNA induces T cells to become phagocytic. Hunter, S., Kamoun, M., Schreiber, A.D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. Acquisition of transforming properties by FYN, a normal SRC-related human gene. Kawakami, T., Kawakami, Y., Aaronson, S.A., Robbins, K.C. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  10. Invasion of human epithelial cells by Pseudomonas aeruginosa involves src-like tyrosine kinases p60Src and p59Fyn. Esen, M., Grassmé, H., Riethmüller, J., Riehle, A., Fassbender, K., Gulbins, E. Infect. Immun. (2001) [Pubmed]
  11. The effects of macrolide and quinolone antibiotics in methicillin-resistant Staphylococcus aureus biofilm growth. Dasgupta, M.K., Shishido, H., Salama, S., Singh, R., Larabie, M., Micetich, R.G. Advances in peritoneal dialysis. Conference on Peritoneal Dialysis. (1997) [Pubmed]
  12. Neither the LCK nor the FYN kinases are obligatory for IL-2-mediated signal transduction in HTLV-I-infected human T cells. Mills, G.B., Arima, N., May, C., Hill, M., Schmandt, R., Li, J., Miyamoto, N.G., Greene, W.C. Int. Immunol. (1992) [Pubmed]
  13. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. Semba, K., Nishizawa, M., Miyajima, N., Yoshida, M.C., Sukegawa, J., Yamanashi, Y., Sasaki, M., Yamamoto, T., Toyoshima, K. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  14. Cleavage and relocation of the tyrosine kinase P59FYN during Fas-mediated apoptosis in T lymphocytes. Ricci, J.E., Maulon, L., Luciano, F., Guerin, S., Livolsi, A., Mari, B., Breittmayer, J.P., Peyron, J.F., Auberger, P. Oncogene (1999) [Pubmed]
  15. Possible role of tyrosine kinase activity in interleukin 4-induced expression of germ-line C epsilon transcripts in a human Burkitt lymphoma B-cell line, DND39. Ikizawa, K., Kajiwara, K., Koshio, T., Yanagihara, Y. J. Allergy Clin. Immunol. (1994) [Pubmed]
  16. Nocodazole inhibits signal transduction by the T cell antigen receptor. Huby, R.D., Weiss, A., Ley, S.C. J. Biol. Chem. (1998) [Pubmed]
  17. Nicotinic acetylcholine receptor subunits and associated proteins in human sperm. Kumar, P., Meizel, S. J. Biol. Chem. (2005) [Pubmed]
  18. Adaptor protein SKAP55R is associated with myeloid differentiation and growth arrest. Curtis, D.J., Jane, S.M., Hilton, D.J., Dougherty, L., Bodine, D.M., Begley, C.G. Exp. Hematol. (2000) [Pubmed]
  19. The solution structure of the intramolecular photoproduct of d(TpA) derived with the use of NMR and a combination of distance geometry and molecular dynamics. Koning, T.M., Davies, R.J., Kaptein, R. Nucleic Acids Res. (1990) [Pubmed]
  20. Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN. L??wenberg, M., Verhaar, A.P., Bilderbeek, J., Marle, J., Buttgereit, F., Peppelenbosch, M.P., van Deventer, S.J., Hommes, D.W. EMBO Rep. (2006) [Pubmed]
  21. Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines. Hallek, M., Neumann, C., Schäffer, M., Danhauser-Riedl, S., von Bubnoff, N., de Vos, G., Druker, B.J., Yasukawa, K., Griffin, J.D., Emmerich, B. Exp. Hematol. (1997) [Pubmed]
  22. The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21. Jackson, A., Panayiotidis, P., Foroni, L. Genomics (1998) [Pubmed]
  23. Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment. Moore, D.J., Masliah, E., Rippeth, J.D., Gonzalez, R., Carey, C.L., Cherner, M., Ellis, R.J., Achim, C.L., Marcotte, T.D., Heaton, R.K., Grant, I. AIDS (2006) [Pubmed]
  24. SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55. Marie-Cardine, A., Verhagen, A.M., Eckerskorn, C., Schraven, B. FEBS Lett. (1998) [Pubmed]
  25. Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes. Price, D.J., Rivnay, B., Fu, Y., Jiang, S., Avraham, S., Avraham, H. J. Biol. Chem. (1997) [Pubmed]
  26. Tyrosine phosphorylation in early embryonic growth cones. Bixby, J.L., Jhabvala, P. J. Neurosci. (1993) [Pubmed]
  27. Neuron-specific splicing of C-SRC RNA in human brain. Pyper, J.M., Bolen, J.B. J. Neurosci. Res. (1989) [Pubmed]
  28. Autophosphorylation promotes complex formation of recombinant hepatocyte growth factor receptor with cytoplasmic effectors containing SH2 domains. Bardelli, A., Maina, F., Gout, I., Fry, M.J., Waterfield, M.D., Comoglio, P.M., Ponzetto, C. Oncogene (1992) [Pubmed]
  29. Detection of low numbers of neuroblastoma cells in vitro. Lai, P.S., Chee, S., Chiu, L.L., Sano, K. Ann. Acad. Med. Singap. (1997) [Pubmed]
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