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Gene Review

CNTN2  -  contactin 2 (axonal)

Homo sapiens

Synonyms: AXT, Axonal glycoprotein TAG-1, Axonin-1, Contactin-2, FAME5, ...
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Disease relevance of CNTN2

  • To address the question of whether 1q32 carries 2 independent amplification targets or a common target other than MDM4 and CNTN2, we analyzed primary malignant gliomas for amplification and overexpression of 17 different genes from this region [1].
  • TAG-1 is expressed in restricted subsets of central and peripheral neurons, not only during development but also in adulthood, and is implicated in neurite outgrowth, axon guidance and fasciculation, as well as neuronal migration [2].
  • Tax1, a potent activator of human T-cell lymphotropic virus type 1 (HTLV-1) transcription, has been shown to modulate expression of many cellular genes [3].
  • Immunohistochemical analysis revealed abundant levels of TAX-1 in neoplastic glial cells of glioblastoma multiforme tumors [4].
  • The involvement of axonin-1/SC2 in mediating notochord-derived chemorepulsive activities for dorsal root ganglion neurites [5].

High impact information on CNTN2

  • The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion [6].
  • We have determined the crystal structure of the ligand binding fragment of the neural cell adhesion molecule axonin-1/TAG-1 comprising the first four immunoglobulin (Ig) domains [6].
  • The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans [7].
  • Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals [7].
  • We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2 [7].

Chemical compound and disease context of CNTN2


Biological context of CNTN2

  • We investigated the domains responsible for the neurite outgrowth promoting activity of TAG-1 as well as its interactions with other cell adhesion molecules [11].
  • The transient axonal glycoprotein TAG-1 induces cell aggregation through homophilic interaction of its fibronectin repeats [11].
  • Like its chicken homologue, the human TAX-1 gene consists of 23 exons [12].
  • The upstream regulatory region of the gene for the human homologue of the adhesion molecule TAG-1 contains elements driving neural specific expression in vivo [2].
  • In an attempt to identify the regulatory elements that guide the neuronal expression of TAG-1, we have isolated genomic clones containing 4 kb of the TAX-1 upstream sequence and used them to drive the expression of the LacZ reporter gene in transgenic mice [2].

Anatomical context of CNTN2


Associations of CNTN2 with chemical compounds

  • While interactions of neurofascin with F11 are only slightly modulated, binding to axonin-1 and TN-R is strongly regulated by alternatively spliced stretches located in the NH2-terminal half, and by the proline-alanine-threonine-rich segment [17].
  • We also show that in vitro-translated NF-YB specifically bound to a glutathione S-transferase-Tax1 fusion protein [3].
  • Polymerase chain reaction (PCR) primers were designed to regions conserved in both TAG-1 and axonin-1 using deoxyinosine at ambiguous positions [18].
  • The three variables studied were 1) the tax1 gene (presence or absence), 2) gender (male or female), and 3) dietary level of folic acid (0.11 or 11.34 mumol folic acid per kilogram of controlled amino acid-based diet) [19].
  • Two regions containing upstream sequences between positions -362/-324 and -323/-276 of the c-fos promoter responded to this activation and also conferred tax1 responsiveness to the heterologous herpesvirus thymidine kinase promoter [20].

Physical interactions of CNTN2

  • However, NF-YB did interact with the C-terminal Tax1 mutants M22 (130TL-AS) and M47 (319LL-RS) [3].

Regulatory relationships of CNTN2

  • These results suggest that axonin-1 is released from the membrane by an endogenously expressed glycosylPtdIns-specific phospholipase D in vivo [8].

Other interactions of CNTN2

  • CNTN2 was found to be coamplified with MDM4 in 3 malignant gliomas but overexpressed in only 1 of these tumors [1].
  • Many of them, including the drosophila fasciclin 1 as well as the mammalian glycoproteins Thy-1, TAG1, N-CAM and F11,F3, contactin are members of the immunoglobulin gene superfamily [21].
  • Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons [22].
  • Further, Tax1 coimmunoprecipitated with NF-Y from nuclear extracts of HTLV-1-transformed cells, providing evidence for in vivo interaction of Tax1 and NF-YB [3].
  • In this study we demonstrate that two neural CAMs, L1-CAM and TAG-1, induce the homophilic aggregation of Drosophila S2 cells but are unable to interact with each other when expressed on different cells (trans-interaction) [16].

Analytical, diagnostic and therapeutic context of CNTN2


  1. Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target. Riemenschneider, M.J., Knobbe, C.B., Reifenberger, G. Int. J. Cancer (2003) [Pubmed]
  2. The upstream regulatory region of the gene for the human homologue of the adhesion molecule TAG-1 contains elements driving neural specific expression in vivo. Denaxa, M., Pavlou, O., Tsiotra, P., Papadopoulos, G.C., Liapaki, K., Theodorakis, K., Papadaki, C., Karagogeos, D., Papamatheakis, J. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  3. Physical and functional interaction between the human T-cell lymphotropic virus type 1 Tax1 protein and the CCAAT binding protein NF-Y. Pise-Masison, C.A., Dittmer, J., Clemens, K.E., Brady, J.N. Mol. Cell. Biol. (1997) [Pubmed]
  4. The gene for the axonal cell adhesion molecule TAX-1 is amplified and aberrantly expressed in malignant gliomas. Rickman, D.S., Tyagi, R., Zhu, X.X., Bobek, M.P., Song, S., Blaivas, M., Misek, D.E., Israel, M.A., Kurnit, D.M., Ross, D.A., Kish, P.E., Hanash, S.M. Cancer Res. (2001) [Pubmed]
  5. The involvement of axonin-1/SC2 in mediating notochord-derived chemorepulsive activities for dorsal root ganglion neurites. Masuda, T., Okado, N., Shiga, T. Dev. Biol. (2000) [Pubmed]
  6. The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion. Freigang, J., Proba, K., Leder, L., Diederichs, K., Sonderegger, P., Welte, W. Cell (2000) [Pubmed]
  7. Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. Fujii, M., Tsuchiya, H., Chuhjo, T., Akizawa, T., Seiki, M. Genes Dev. (1992) [Pubmed]
  8. The neuronal cell-adhesion molecule axonin-1 is specifically released by an endogenous glycosylphosphatidylinositol-specific phospholipase. Lierheimer, R., Kunz, B., Vogt, L., Savoca, R., Brodbeck, U., Sonderegger, P. Eur. J. Biochem. (1997) [Pubmed]
  9. Intracellular signaling is changed after clustering of the neural cell adhesion molecules axonin-1 and NgCAM during neurite fasciculation. Kunz, S., Ziegler, U., Kunz, B., Sonderegger, P. J. Cell Biol. (1996) [Pubmed]
  10. Thauera selenatis gen. nov., sp. nov., a member of the beta subclass of Proteobacteria with a novel type of anaerobic respiration. Macy, J.M., Rech, S., Auling, G., Dorsch, M., Stackebrandt, E., Sly, L.I. Int. J. Syst. Bacteriol. (1993) [Pubmed]
  11. Analysis of interactions of the adhesion molecule TAG-1 and its domains with other immunoglobulin superfamily members. Pavlou, O., Theodorakis, K., Falk, J., Kutsche, M., Schachner, M., Faivre-Sarrailh, C., Karagogeos, D. Mol. Cell. Neurosci. (2002) [Pubmed]
  12. The human TAX1 gene encoding the axon-associated cell adhesion molecule TAG-1/axonin-1: genomic structure and basic promoter. Kozlov, S.V., Giger, R.J., Hasler, T., Korvatska, E., Schorderet, D.F., Sonderegger, P. Genomics (1995) [Pubmed]
  13. Transgenic mice expressing F3/contactin from the TAG-1 promoter exhibit developmentally regulated changes in the differentiation of cerebellar neurons. Bizzoca, A., Virgintino, D., Lorusso, L., Buttiglione, M., Yoshida, L., Polizzi, A., Tattoli, M., Cagiano, R., Rossi, F., Kozlov, S., Furley, A., Gennarini, G. Development (2003) [Pubmed]
  14. Spatial regulation of axonal glycoprotein expression on subsets of embryonic spinal neurons. Dodd, J., Morton, S.B., Karagogeos, D., Yamamoto, M., Jessell, T.M. Neuron (1988) [Pubmed]
  15. Implications for the domain arrangement of axonin-1 derived from the mapping of its NgCAM binding site. Rader, C., Kunz, B., Lierheimer, R., Giger, R.J., Berger, P., Tittmann, P., Gross, H., Sonderegger, P. EMBO J. (1996) [Pubmed]
  16. Cis-activation of L1-mediated ankyrin recruitment by TAG-1 homophilic cell adhesion. Malhotra, J.D., Tsiotra, P., Karagogeos, D., Hortsch, M. J. Biol. Chem. (1998) [Pubmed]
  17. Dissection of complex molecular interactions of neurofascin with axonin-1, F11, and tenascin-R, which promote attachment and neurite formation of tectal cells. Volkmer, H., Zacharias, U., Nörenberg, U., Rathjen, F.G. J. Cell Biol. (1998) [Pubmed]
  18. cDNA cloning, structural features, and eucaryotic expression of human TAG-1/axonin-1. Hasler, T.H., Rader, C., Stoeckli, E.T., Zuellig, R.A., Sonderegger, P. Eur. J. Biochem. (1993) [Pubmed]
  19. Delayed tumor onset in transgenic mice fed a low-folate diet. Bills, N.D., Hinrichs, S.H., Morgan, R., Clifford, A.J. J. Natl. Cancer Inst. (1992) [Pubmed]
  20. c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I. Fujii, M., Sassone-Corsi, P., Verma, I.M. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  21. Glycosylphosphatidylinositol anchored recognition molecules that function in axonal fasciculation, growth and guidance in the nervous system. Walsh, F.S., Doherty, P. Cell Biol. Int. Rep. (1991) [Pubmed]
  22. Interference with axonin-1 and NrCAM interactions unmasks a floor-plate activity inhibitory for commissural axons. Stoeckli, E.T., Sonderegger, P., Pollerberg, G.E., Landmesser, L.T. Neuron (1997) [Pubmed]
  23. Neurite outgrowth on immobilized axonin-1 is mediated by a heterophilic interaction with L1(G4). Kuhn, T.B., Stoeckli, E.T., Condrau, M.A., Rathjen, F.G., Sonderegger, P. J. Cell Biol. (1991) [Pubmed]
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