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Gene Review

TFG  -  TRK-fused gene

Homo sapiens

Synonyms: FLJ36137, HMSNP, SPG57, TF6, TRKT3
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Disease relevance of TFG

  • Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity [1].
  • TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma [2].
  • RESULTS: A RS <0% was associated with greater gains in lumen diameter and smaller reference diameters after PCI (p < 0.001 for each), with a trend toward less frequent Thrombolysis In Myocardial Infarction flow grade (TFG) 3 [3].
  • In the present study, we investigated the association of transforming growth factor-beta 1 (TFG-beta 1) gene expression in human liver disease [4].
  • We conclude that extracellular calmodulin should be considered, in addition to PDGF, TFG-beta and EGF, as a potential mitogen involved in the stromal reaction of idiopathic myelofibrosis [5].

High impact information on TFG

  • The organizer is formed in an equatorial sector of the blastula stage amphibian embryo by cells that have responded to two maternal agents: a general mesoendoderm inducer (involving the TFG-beta signaling pathway) and a dorsal modifier (probably involving the Wnt signaling pathway) [6].
  • Here we have identified TRK-fused gene (TFG) as a new ALK partner in 2 ALCL, 1 of which exhibited a t(2;3)(p23;q21) [7].
  • The breakpoint producing the TRK-T3 oncogene occurs within exons of both the TFG gene and the NTRK1 gene and produces a chimeric exon that undergoes alternative splicing [8].
  • The TFG gene is ubiquitously expressed and is located on chromosome 3 [8].
  • The TRK-T3 amino acid sequence displays, within the TFG region, a coiled-coil motif that could endow the oncoprotein with the capability to form complexes [8].

Chemical compound and disease context of TFG


Biological context of TFG

  • Encoding a protein with a putative coiled-coil structure, TFG previously was identified by a homology search in the Expressed Sequence Tag Database as having an SPYGQ-rich region similar to the N-terminal parts of EWS and TLS [2].
  • We found 100% identity between the 5' part of the consensus sequence and the 598-bp-long sequence named TFG [10].
  • We hypothesized that endothelial activation, as measured by a rise in von Willebrand Factor (DeltavWF), was influenced by the thrombolysis in myocardial infarction flow grade (TFG), the corrected TIMI frame count (CTFC) and the choice of anticoagulant therapy after fibrinolysis in ST elevation myocardial infarction (STEMI) [11].
  • Thus, DSA validates that TMPG 3 is associated with normal kinetics of myocardial perfusion, and this likely accounts for the low (0.7%) 30 day mortality observed among those patients with TFG 3 and TMPG 3 [12].
  • We did not observe great differences in cell proliferation and TFG-beta secretion [13].

Anatomical context of TFG

  • The thyroid TRK-T3 oncogene consists of the NTRK1 tyrosine kinase domain fused in-frame with sequences of the TFG (TRK-fused gene), encoding a protein of unknown function [14].
  • In situ hybridization with a TFG probe in 10, 5-day whole mouse embryos showed preferential staining of the limb buds, branchial arches, nasal processes, and brain, and weak staining of the primitive spinal cord and dorsal root ganglia [15].
  • Transforming growth factor beta (TFG-beta) is a multifunctional growth factor that promotes the growth of fibroblasts, collagen synthesis and angiogenesis, and stimulates monocyte migration and activation, but suppresses the growth and differentiation of immune lymphocytes and killer cells [16].
  • In each experiment, some of the subjects received true feedback (TFG), while others received reverse, or false, feedback (RFG) about the pH of their stomach contents [17].
  • These results suggest that growth factors such as TFG alpha or FGF, which may be derived from the adjacent mammary stroma, might influence in a paracrine manner the phenotypic characteristics of a population of human mammary epithelial cells toward transformation [18].

Associations of TFG with chemical compounds

  • Spinal serotonergic system, but not endogenous opioid system, was involved in TFG induced analgesia (in the second phase of formalin test) [19].
  • Trifluoromethylated a-diketone (TF1, CF3COCOPh) and alpha-hydroxy ketones (TF2, CF3CH(OH)COPh; TF3, CF3CH(OH)COCH2Ph) showed higher tumor-specific cytotoxic activity than the corresponding non-fluorinated analogs (TF5, CH3COCOPh; TF6, CH3CH(OH)COPh), while the anti-tumor potency of trifluoromethyl ketone (TF4, CF3COCH2Ph) was lower [20].

Physical interactions of TFG

  • Based on the presence of a putative SHP-1 SH2-binding site within the TFG sequences, we have investigated the role of the SHP-1 phosphatase in TRK-T3 oncoprotein signaling [14].
  • The effect of TGF-beta on cell surface binding was maximal after 2 h of exposure to TFG-beta and did not require epidermal growth factor or protein synthesis [21].

Other interactions of TFG

  • Moreover, it reveals TFG as a novel protein able to modulate SHP-1 activity [14].
  • The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway [22].
  • The thyroid TRK oncogenes are activated by recombination with at least three different genes: the gene coding for tropomyosin and TPR, both on chromosome 1,and TFG on chromosome 3 [23].
  • The profile of TGF beta 1 binding proteins was the same in HMEC that were, and were not growth suppressed by TFG beta [24].
  • These RT-PCR findings were confirmed using immunohistochemical staining of EGF and TFG-beta, whereas TGF-alpha protein was always found associated with discocytes [25].

Analytical, diagnostic and therapeutic context of TFG


  1. Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity. Hernández, L., Beà, S., Bellosillo, B., Pinyol, M., Falini, B., Carbone, A., Ott, G., Rosenwald, A., Fernández, A., Pulford, K., Mason, D., Morris, S.W., Santos, E., Campo, E. Am. J. Pathol. (2002) [Pubmed]
  2. TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Hisaoka, M., Ishida, T., Imamura, T., Hashimoto, H. Genes Chromosomes Cancer (2004) [Pubmed]
  3. Association of a negative residual stenosis following rescue/adjunctive percutaneous coronary intervention with impaired myocardial perfusion and adverse outcomes among ST-segment elevation myocardial infarction patients. Gibson, C.M., Kirtane, A.J., Boundy, K., Ly, H., Karmpaliotis, D., Murphy, S.A., Giugliano, R.P., Cannon, C.P., Antman, E.M., Braunwald, E. J. Am. Coll. Cardiol. (2005) [Pubmed]
  4. Increased transforming growth factor-beta 1 gene expression in human liver disease. Annoni, G., Weiner, F.R., Zern, M.A. J. Hepatol. (1992) [Pubmed]
  5. Investigation of calmodulin and basic fibroblast growth factor (bFGF) in idiopathic myelofibrosis: evidence for a role of extracellular calmodulin in fibroblast proliferation. Dalley, A., Smith, J.M., Reilly, J.T., Neil, S.M. Br. J. Haematol. (1996) [Pubmed]
  6. Formation and function of Spemann's organizer. Harland, R., Gerhart, J. Annu. Rev. Cell Dev. Biol. (1997) [Pubmed]
  7. TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. Hernández, L., Pinyol, M., Hernández, S., Beà, S., Pulford, K., Rosenwald, A., Lamant, L., Falini, B., Ott, G., Mason, D.Y., Delsol, G., Campo, E. Blood (1999) [Pubmed]
  8. The DNA rearrangement that generates the TRK-T3 oncogene involves a novel gene on chromosome 3 whose product has a potential coiled-coil domain. Greco, A., Mariani, C., Miranda, C., Lupas, A., Pagliardini, S., Pomati, M., Pierotti, M.A. Mol. Cell. Biol. (1995) [Pubmed]
  9. Vitamin A and causes of maternal mortality: association and biological plausibility. Faisel, H., Pittrof, R. Public health nutrition. (2000) [Pubmed]
  10. Characterization and chromosomal mapping of the human TFG gene involved in thyroid carcinoma. Mencinger, M., Panagopoulos, I., Andreasson, P., Lassen, C., Mitelman, F., Aman, P. Genomics (1997) [Pubmed]
  11. Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome: An ENTIRE-TIMI 23 substudy. Ray, K.K., Morrow, D.A., Gibson, C.M., Murphy, S., Antman, E.M., Braunwald, E. Eur. Heart J. (2005) [Pubmed]
  12. Methodologic and clinical validation of the TIMI myocardial perfusion grade in acute myocardial infarction. Gibson, C.M., de Lemos, J.A., Murphy, S.A., Marble, S.J., Dauterman, K.W., Michaels, A., Barron, H.V., Antman, E.M. J. Thromb. Thrombolysis (2002) [Pubmed]
  13. Potential of human bone marrow stromal cells to accelerate wound healing in vitro. Han, S.K., Yoon, T.H., Lee, D.G., Lee, M.A., Kim, W.K. Annals of plastic surgery. (2005) [Pubmed]
  14. Analysis of SHP-1-mediated down-regulation of the TRK-T3 oncoprotein identifies Trk-fused gene (TFG) as a novel SHP-1-interacting protein. Roccato, E., Miranda, C., Raho, G., Pagliardini, S., Pierotti, M.A., Greco, A. J. Biol. Chem. (2005) [Pubmed]
  15. Characterization of TFG in mus musculus and Caenorhabditis elegans. Mencinger, M., Aman, P. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  16. Immunohistochemical evidence of a role for transforming growth factor beta in the pathogenesis of nodular sclerosing Hodgkin's disease. Kadin, M.E., Agnarsson, B.A., Ellingsworth, L.R., Newcom, S.R. Am. J. Pathol. (1990) [Pubmed]
  17. Experimental modification of digestive pathology. Welgan, P.R. Neuroscience and biobehavioral reviews. (1981) [Pubmed]
  18. Stromal influences on transformation of human mammary epithelial cells overexpressing c-myc and SV40T. Valverius, E.M., Ciardiello, F., Heldin, N.E., Blondel, B., Merlo, G., Smith, G., Stampfer, M.R., Lippman, M.E., Dickson, R.B., Salomon, D.S. J. Cell. Physiol. (1990) [Pubmed]
  19. Probable role of spinal purinoceptors in the analgesic effect of Trigonella foenum (TFG) leaves extract. Parvizpur, A., Ahmadiani, A., Kamalinejad, M. Journal of ethnopharmacology. (2006) [Pubmed]
  20. Cytotoxic activity of selected trifluoromethyl ketones against oral tumor cells. Ideo, A., Sasaki, M., Nakamura, C., Mori, K., Shimada, J., Kanda, Y., Kunii, S., Kawase, M., Sakagami, H. Anticancer Res. (2006) [Pubmed]
  21. Transforming growth factor beta increases cell surface binding and assembly of exogenous (plasma) fibronectin by normal human fibroblasts. Allen-Hoffmann, B.L., Crankshaw, C.L., Mosher, D.F. Mol. Cell. Biol. (1988) [Pubmed]
  22. The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway. Miranda, C., Roccato, E., Raho, G., Pagliardini, S., Pierotti, M.A., Greco, A. J. Cell. Physiol. (2006) [Pubmed]
  23. Chromosome 1 rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes. Greco, A., Miranda, C., Pagliardini, S., Fusetti, L., Bongarzone, I., Pierotti, M.A. Genes Chromosomes Cancer (1997) [Pubmed]
  24. TGF beta induction of extracellular matrix associated proteins in normal and transformed human mammary epithelial cells in culture is independent of growth effects. Stampfer, M.R., Yaswen, P., Alhadeff, M., Hosoda, J. J. Cell. Physiol. (1993) [Pubmed]
  25. Transforming and epidermal growth factors in degenerated intervertebral discs. Konttinen, Y.T., Kemppinen, P., Li, T.F., Waris, E., Pihlajamäki, H., Sorsa, T., Takagi, M., Santavirta, S., Schultz, G.S., Humphreys-Beher, M.G. The Journal of bone and joint surgery. British volume. (1999) [Pubmed]
  26. Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and myocardial reperfusion. Giugliano, R.P., Sabatine, M.S., Gibson, C.M., Roe, M.T., Harrington, R.A., Murphy, S.A., Morrow, D.A., Antman, E.M., Braunwald, E. Am. J. Cardiol. (2004) [Pubmed]
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