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Gene Review

CNTNAP1  -  contactin associated protein 1

Homo sapiens

Synonyms: CASPR, CNTNAP, Caspr, Caspr1, Contactin-associated protein 1, ...
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Disease relevance of CNTNAP1


High impact information on CNTNAP1

  • From its novel two-chain structure, we deduced that p190 was the prototype of a new class of tyrosine kinase receptors [6].
  • We also show that the high level of p190 found in the GTL-16 cell line is accompanied by amplification and overexpression of c-met [6].
  • Our evidence indicates that purified p190 can alter the course of parasitaemia in monkeys with falciparum malaria [5].
  • P190 BCR/ABL induced lymphoid leukemia with shorter latency than P210 or P230 [7].
  • Paranodin/contactin-associated protein (caspr) is a transmembrane glycoprotein of the neurexin superfamily that is highly enriched in the paranodal regions of myelinated axons [8].

Chemical compound and disease context of CNTNAP1


Biological context of CNTNAP1

  • In this study, we physically mapped the Caspr1 gene on chromosome 17q21.1 and determined its genomic structure [1].
  • We found that activation of v-Src induced association of tyrosine phosphorylated p190 with p120(RasGAP) and stimulation of p120(RasGAP)-associated RhoGAP activity, although p120(RasGAP) itself was not a target for phosphorylation by v-Src in chicken embryo cells [14].
  • Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and 3BP-1 [15].
  • We now show that p190 is indistinguishable from the protein encoded by the c-met proto-oncogene and that the alpha beta-subunit structure is conserved in other human cell lines [6].
  • Ph(+) ALL cells harbor a bcrabl fusion gene (e1a2) encoding a 190-kDa fusion protein (p190) involved in disease pathogenesis [16].

Anatomical context of CNTNAP1

  • Since molecular alterations in septate-like junctions at the paranodes might have important consequences for the function of the nerve fiber, we considered that Caspr1 could be involved in the pathogenesis of inherited peripheral neuropathies [1].
  • Furthermore, these effects were rapidly reversible since switching off v-Src led to dissociation of the p190/p120(RasGAP) complex, inactivation of p120(RasGAP)-associated RhoGAP activity and re-induction of actin stress fibres [14].
  • NF-Fc significantly inhibited nodal clustering of Na(+) channels, ankyrin(G), and betaIV spectrin, and modestly reduced Caspr clustering at paranodal junctions; it did not significantly affect lengths or numbers of myelin-positive segments, axon initial segments, or accumulations of phosphorylated-ERM proteins in Schwann cell nodal microvilli [17].
  • In both peripheral and central nervous systems, some paranodal loops failed to attach to the axolemma, and immunostaining of Caspr and NF155 was attenuated [18].
  • Changes occurring in the transition from the soluble to membrane-bound state of the C-terminal 190-residue channel polypeptide of colicin E1 (P190) bound to anionic membranes are described [19].

Associations of CNTNAP1 with chemical compounds

  • Under conditions of estradiol-dependent growth, estradiol treatment of human mammary cancer MCF-7 cells triggers rapid and transient activation of the mitogen-activated (MAP) kinases, erk-1 and erk-2, increases the active form of p21ras, tyrosine phosphorylation of Shc and p190 protein and induces association of p190 to p21ras-GAP [20].
  • In this report, we demonstrate that RA-induced CD38 protein from human myeloid (HL-60) leukemia cells coimmunoprecipitates with another protein of molecular mass approximately190 kDa (p190) [21].
  • Inhibition by p190 was prevented by GTP gamma S, a nonhydrolyzable analogue of GTP [22].
  • We suggest that activation of the alpha6beta1 integrin signaling regulates the tyrosine phosphorylation state of p190 which in turn connects downstream signaling pathways through Rho family GTPases to actin cytoskeleton in invadopodia, thus promoting membrane-protrusive and degradative activities necessary for cell invasion [23].
  • To characterize the p120.p190 interaction further, we used bacterially expressed glutathione S-transferase fusion polypeptides to map the regions of p120 necessary for its interactions with p190 [24].

Other interactions of CNTNAP1

  • The catalytic efficiencies (Kcat/Km) of the GAP domains of Bcr, 3BP-1, and p190 on Cdc42 are found to be 60-, 160-, and over 500-fold less than that of Cdc42GAP, respectively, and the differences are due, to a large part, to differences in Km [25].
  • p120GAP forms distinct complexes with two phosphoproteins, p62 and p190 [26].
  • Partial sequence analysis of rhoGAP has led to the identification of a family of related proteins which now includes bcr, chimaerin, p190, p85, and 3BP-1 [27].
  • The MRD1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes [28].
  • Follow up of patient 1 showed a progressive increase in WT-1 and in p-190 transcript, which was followed by cytogenetic and hematological relapse [29].

Analytical, diagnostic and therapeutic context of CNTNAP1

  • In cells from 24 leukemias, single bcr-abl PCR products were detected that corresponded to breakpoints in the minor breakpoint cluster region (mbcr in intron 1 of the bcr gene) associated with production of the P190 fusion protein [30].
  • Moreover, using a novel and very sensitive Western blot technique, we detected relevant amounts of P190 protein in addition to P210 from peripheral cells of two of the patients [31].
  • BCR-ABL RT-PCR is confirmed as a sensitive, rapid method to diagnose t(9;22), and p190 and p210 are unequivocally demonstrated as the most important predictors of poor long-term survival despite intensified chemotherapy [32].
  • By immunoprecipitation of surface-labeled CD45 molecules from MN thymocytes, a proportion of the CD45 is in fact of low molecular mass but does not include epitopes recognized by CD45R0, nor by CD45RB mAb specific for the p190 [33].
  • In addition, the localized matrix degradation and membrane-protrusive activities were blocked by treatment of LOX cells with tyrosine kinase inhibitors as well as microinjection of antibodies directed against p190 but not by non-perturbing antibodies or control buffers [23].


  1. Caspr1/Paranodin/Neurexin IV is most likely not a common disease-causing gene for inherited peripheral neuropathies. Venken, K., Meuleman, J., Irobi, J., Ceuterick, C., Martini, R., De Jonghe, P., Timmerman, V. Neuroreport (2001) [Pubmed]
  2. Distinct but Overlapping Functions for the Closely Related p190 RhoGAPs in Neural Development. Matheson, S.F., Hu, K.Q., Brouns, M.R., Sordella, R., Vanderheide, J.D., Settleman, J. Dev. Neurosci. (2006) [Pubmed]
  3. Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis. Coman, I., Aigrot, M.S., Seilhean, D., Reynolds, R., Girault, J.A., Zalc, B., Lubetzki, C. Brain (2006) [Pubmed]
  4. Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. Korsmeyer, S.J. Annu. Rev. Immunol. (1992) [Pubmed]
  5. Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. Hall, R., Hyde, J.E., Goman, M., Simmons, D.L., Hope, I.A., Mackay, M., Scaife, J., Merkli, B., Richle, R., Stocker, J. Nature (1984) [Pubmed]
  6. Tyrosine kinase receptor indistinguishable from the c-met protein. Giordano, S., Ponzetto, C., Di Renzo, M.F., Cooper, C.S., Comoglio, P.M. Nature (1989) [Pubmed]
  7. The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. Li, S., Ilaria, R.L., Million, R.P., Daley, G.Q., Van Etten, R.A. J. Exp. Med. (1999) [Pubmed]
  8. The glycosylphosphatidyl inositol-anchored adhesion molecule F3/contactin is required for surface transport of paranodin/contactin-associated protein (caspr). Faivre-Sarrailh, C., Gauthier, F., Denisenko-Nehrbass, N., Le Bivic, A., Rougon, G., Girault, J.A. J. Cell Biol. (2000) [Pubmed]
  9. Resistance to imatinib of bcr/abl p190 lymphoblastic leukemia cells. Mishra, S., Zhang, B., Cunnick, J.M., Heisterkamp, N., Groffen, J. Cancer Res. (2006) [Pubmed]
  10. Analysis of P210bcr-abl tyrosine protein kinase activity in various subtypes of Philadelphia chromosome-positive cells from chronic myelogenous leukemia patients. Maxwell, S.A., Kurzrock, R., Parsons, S.J., Talpaz, M., Gallick, G.E., Kloetzer, W.S., Arlinghaus, R.B., Kouttab, N.M., Keating, M.J., Gutterman, J.U. Cancer Res. (1987) [Pubmed]
  11. Treatment of P190 Bcr/Abl lymphoblastic leukemia cells with inhibitors of the serine/threonine kinase CK2. Mishra, S., Pertz, V., Zhang, B., Kaur, P., Shimada, H., Groffen, J., Kazimierczuk, Z., Pinna, L.A., Heisterkamp, N. Leukemia (2007) [Pubmed]
  12. AMN107, a novel aminopyrimidine inhibitor of p190 Bcr-Abl activation and of in vitro proliferation of Philadelphia-positive acute lymphoblastic leukemia cells. Verstovsek, S., Golemovic, M., Kantarjian, H., Manshouri, T., Estrov, Z., Manley, P., Sun, T., Arlinghaus, R.B., Alland, L., Dugan, M., Cortes, J., Giles, F., Beran, M. Cancer (2005) [Pubmed]
  13. Non-P-glycoprotein multidrug resistance in cell lines which are defective in the cellular accumulation of drug. Center, M.S. Cytotechnology. (1993) [Pubmed]
  14. Regulation of p190 Rho-GAP by v-Src is linked to cytoskeletal disruption during transformation. Fincham, V.J., Chudleigh, A., Frame, M.C. J. Cell. Sci. (1999) [Pubmed]
  15. Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and 3BP-1. Zhang, B., Zheng, Y. Biochemistry (1998) [Pubmed]
  16. A novel maxizyme vector targeting a bcr-abl fusion gene induced specific cell death in Philadelphia chromosome-positive acute lymphoblastic leukemia. Soda, Y., Tani, K., Bai, Y., Saiki, M., Chen, M., Izawa, K., Kobayashi, S., Takahashi, S., Uchimaru, K., Kuwabara, T., Warashina, M., Tanabe, T., Miyoshi, H., Sugita, K., Nakazawa, S., Tojo, A., Taira, K., Asano, S. Blood (2004) [Pubmed]
  17. Neurofascin interactions play a critical role in clustering sodium channels, ankyrin(G) and betaIV spectrin at peripheral nodes of Ranvier. Koticha, D., Maurel, P., Zanazzi, G., Kane-Goldsmith, N., Basak, S., Babiarz, J., Salzer, J., Grumet, M. Dev. Biol. (2006) [Pubmed]
  18. Gangliosides contribute to stability of paranodal junctions and ion channel clusters in myelinated nerve fibers. Susuki, K., Baba, H., Tohyama, K., Kanai, K., Kuwabara, S., Hirata, K., Furukawa, K., Furukawa, K., Rasband, M.N., Yuki, N. Glia (2007) [Pubmed]
  19. Membrane-bound state of the colicin E1 channel domain as an extended two-dimensional helical array. Zakharov, S.D., Lindeberg, M., Griko, Y., Salamon, Z., Tollin, G., Prendergast, F.G., Cramer, W.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  20. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. Migliaccio, A., Di Domenico, M., Castoria, G., de Falco, A., Bontempo, P., Nola, E., Auricchio, F. EMBO J. (1996) [Pubmed]
  21. Post-translational modification of CD38 protein into a high molecular weight form alters its catalytic properties. Umar, S., Malavasi, F., Mehta, K. J. Biol. Chem. (1996) [Pubmed]
  22. Regulation of NADPH oxidase activity by Rac GTPase activating protein(s). Heyworth, P.G., Knaus, U.G., Settleman, J., Curnutte, J.T., Bokoch, G.M. Mol. Biol. Cell (1993) [Pubmed]
  23. Activation of beta1 integrin signaling stimulates tyrosine phosphorylation of p190RhoGAP and membrane-protrusive activities at invadopodia. Nakahara, H., Mueller, S.C., Nomizu, M., Yamada, Y., Yeh, Y., Chen, W.T. J. Biol. Chem. (1998) [Pubmed]
  24. Two SH2 domains of p120 Ras GTPase-activating protein bind synergistically to tyrosine phosphorylated p190 Rho GTPase-activating protein. Bryant, S.S., Briggs, S., Smithgall, T.E., Martin, G.A., McCormick, F., Chang, J.H., Parsons, S.J., Jove, R. J. Biol. Chem. (1995) [Pubmed]
  25. Characterization of the interactions between the small GTPase Cdc42 and its GTPase-activating proteins and putative effectors. Comparison of kinetic properties of Cdc42 binding to the Cdc42-interactive domains. Zhang, B., Wang, Z.X., Zheng, Y. J. Biol. Chem. (1997) [Pubmed]
  26. p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking. Burbelo, P.D., Miyamoto, S., Utani, A., Brill, S., Yamada, K.M., Hall, A., Yamada, Y. J. Biol. Chem. (1995) [Pubmed]
  27. Characterization of rhoGAP. A GTPase-activating protein for rho-related small GTPases. Lancaster, C.A., Taylor-Harris, P.M., Self, A.J., Brill, S., van Erp, H.E., Hall, A. J. Biol. Chem. (1994) [Pubmed]
  28. The MRD1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes. Martel, J., Payet, M.D., Dupuis, G. Leuk. Res. (1997) [Pubmed]
  29. Monitoring molecular response by BCR-ABL, JH and WT-1 in Ph+ all treated with imatinib containing regimen: preliminary report of two cases. Miglino, M., Varaldo, R., Colombo, N., Grasso, R., Clavio, M., Garuti, A., Aquino, S., Albarello, A., Sessarego, M., Gobbi, M. J. Exp. Clin. Cancer Res. (2006) [Pubmed]
  30. Consistent involvement of the bcr gene by 9;22 breakpoints in pediatric acute leukemias. Suryanarayan, K., Hunger, S.P., Kohler, S., Carroll, A.J., Crist, W., Link, M.P., Cleary, M.L. Blood (1991) [Pubmed]
  31. Consistent amounts of acute leukemia-associated P190BCR/ABL transcripts are expressed by chronic myelogenous leukemia patients at diagnosis. Saglio, G., Pane, F., Gottardi, E., Frigeri, F., Buonaiuto, M.R., Guerrasio, A., de Micheli, D., Parziale, A., Fornaci, M.N., Martinelli, G., Salvatore, F. Blood (1996) [Pubmed]
  32. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Gleissner, B., Gökbuget, N., Bartram, C.R., Janssen, B., Rieder, H., Janssen, J.W., Fonatsch, C., Heyll, A., Voliotis, D., Beck, J., Lipp, T., Munzert, G., Maurer, J., Hoelzer, D., Thiel, E. Blood (2002) [Pubmed]
  33. Prolonged expression of high molecular mass CD45RA isoform during the differentiation of human progenitor thymocytes to CD3+ cells in vitro. Deans, J.P., Wilkins, J.A., Caixia, S., Pruski, E., Pilarski, L.M. J. Immunol. (1991) [Pubmed]
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