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Gene Review

NRXN1  -  neurexin 1

Homo sapiens

Synonyms: Hs.22998, KIAA0578, PTHSL2, SCZD17
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High impact information on NRXN1

  • Neuroligation: building synapses around the neurexin-neuroligin link [1].
  • The three-dimensional structures of LG/LNS domains from neurexin, the laminin alpha 2 chain and sex hormone-binding globulin reveal a close structural relationship to the carbohydrate-binding pentraxins and other lectins [2].
  • Thousands of neurexin isoforms are generated from three genes by usage of alternative promoters and alternative splicing [3].
  • This review describes the properties of the neurexin protein family and their potential roles in neuronal cell adhesion and intercellular signaling [3].
  • Our study nominates several novel genes, such as Neurexin 1 (NRXN1), in the development of nicotine dependence while also identifying a known candidate gene, the beta3 nicotinic cholinergic receptor [4].

Biological context of NRXN1


Anatomical context of NRXN1


Associations of NRXN1 with chemical compounds

  • Interestingly, on subsequent removal of Ca(2+), alpha-latrotoxin dissociates from neurexin but remains in the membrane and continues to form pores [10].
  • In skeletal muscle, dystroglycan is a component of the dystrophin-glycoprotein complex. alpha-Dystroglycan is an extracellular peripheral membrane glycoprotein that binds to beta-dystroglycan, which is a transmembrane glycoprotein. alpha-Dystroglycan is heavily glycosylated and its sugars have a role in binding to laminin, neurexin and agrin [11].

Physical interactions of NRXN1

  • The three-dimensional models of the AF-6 PDZ-Neurexin C-terminal peptide complex and the AF-6 PDZ-Bcr C-terminal peptide complex were built up by molecular dynamics simulations [12].
  • The paired, but not the isolated PDZ domains of syntenin bind also strongly to the immobilized cytoplasmic domains of neurexin and B-class ephrins [13].

Other interactions of NRXN1

  • Unexpectedly, two of these, NRXN1 ( approximately 1.1 Mb) and NRXN3 ( approximately 1.7 Mb), are among the largest known human genes [5].
  • Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr [12].
  • Neuroligin and neurexin form an intercellular adhesion complex sufficient to trigger formation of functional presynaptic elements in vitro [14].
  • We report the expression of neurexin 1, Neuro D1, dlx1, and dlx2 in untreated and cAMP treated epithelial prostate cells [15].
  • Recently, the three-dimensional (3D) structure of LG domains from plasma SHBG, laminin and neurexin have been reported and were found related to the pentraxin family [16].

Analytical, diagnostic and therapeutic context of NRXN1


  1. Neuroligation: building synapses around the neurexin-neuroligin link. Rao, A., Harms, K.J., Craig, A.M. Nat. Neurosci. (2000) [Pubmed]
  2. LG/LNS domains: multiple functions -- one business end? Rudenko, G., Hohenester, E., Muller, Y.A. Trends Biochem. Sci. (2001) [Pubmed]
  3. Neurexins: three genes and 1001 products. Missler, M., Südhof, T.C. Trends Genet. (1998) [Pubmed]
  4. Novel genes identified in a high-density genome wide association study for nicotine dependence. Bierut, L.J., Madden, P.A., Breslau, N., Johnson, E.O., Hatsukami, D., Pomerleau, O.F., Swan, G.E., Rutter, J., Bertelsen, S., Fox, L., Fugman, D., Goate, A.M., Hinrichs, A.L., Konvicka, K., Martin, N.G., Montgomery, G.W., Saccone, N.L., Saccone, S.F., Wang, J.C., Chase, G.A., Rice, J.P., Ballinger, D.G. Hum. Mol. Genet. (2007) [Pubmed]
  5. Analysis of the human neurexin genes: alternative splicing and the generation of protein diversity. Rowen, L., Young, J., Birditt, B., Kaur, A., Madan, A., Philipps, D.L., Qin, S., Minx, P., Wilson, R.K., Hood, L., Graveley, B.R. Genomics (2002) [Pubmed]
  6. A 500-kb sequence-ready cosmid contig and transcript map of the MEN1 region on 11q13. Bergman, L., Silins, G., Grimmond, S., Hummerich, H., Stewart, C., Little, P., Hayward, N. Genomics (1999) [Pubmed]
  7. BMP growth factors and Phox2 transcription factors can induce synaptotagmin I and neurexin I during sympathetic neuron development. Patzke, H., Reissmann, E., Stanke, M., Bixby, J.L., Ernsberger, U. Mech. Dev. (2001) [Pubmed]
  8. Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Ibeta gene expression followed by late-onset neuromotor deterioration. Andres, C., Beeri, R., Friedman, A., Lev-Lehman, E., Henis, S., Timberg, R., Shani, M., Soreq, H. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Solution structure of GOPC PDZ domain and its interaction with the C-terminal motif of neuroligin. Li, X., Zhang, J., Cao, Z., Wu, J., Shi, Y. Protein Sci. (2006) [Pubmed]
  10. Latrophilin, neurexin, and their signaling-deficient mutants facilitate alpha -latrotoxin insertion into membranes but are not involved in pore formation. Volynski, K.E., Meunier, F.A., Lelianova, V.G., Dudina, E.E., Volkova, T.M., Rahman, M.A., Manser, C., Grishin, E.V., Dolly, J.O., Ashley, R.H., Ushkaryov, Y.A. J. Biol. Chem. (2000) [Pubmed]
  11. Aberrant glycosylation of alpha-dystroglycan and congenital muscular dystrophies. Endo, T. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases. (2005) [Pubmed]
  12. Solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr. Zhou, H., Xu, Y., Yang, Y., Huang, A., Wu, J., Shi, Y. J. Biol. Chem. (2005) [Pubmed]
  13. Syntenin-syndecan binding requires syndecan-synteny and the co-operation of both PDZ domains of syntenin. Grootjans, J.J., Reekmans, G., Ceulemans, H., David, G. J. Biol. Chem. (2000) [Pubmed]
  14. Synapse formation: if it looks like a duck and quacks like a duck .... Cantallops, I., Cline, H.T. Curr. Biol. (2000) [Pubmed]
  15. cAMP induced modifications of HOX D gene expression in prostate cells allow the identification of a chromosomal area involved in vivo with neuroendocrine differentiation of human advanced prostate cancers. Cantile, M., Kisslinger, A., Cindolo, L., Schiavo, G., D'Antò, V., Franco, R., Altieri, V., Gallo, A., Villacci, A., Tramontano, D., Cillo, C. J. Cell. Physiol. (2005) [Pubmed]
  16. Three-dimensional model of the SHBG-like region of anticoagulant protein S: new structure-function insights. Villoutreix, B.O., Dahlbäck, B., Borgel, D., Gandrille, S., Muller, Y.A. Proteins (2001) [Pubmed]
  17. Reduction of endogenous TGF-beta does not affect phenotypic development of sympathoadrenal progenitors into adrenal chromaffin cells. Combs, S.E., Ernsberger, U., Krieglstein, K., Unsicker, K. Mech. Dev. (2001) [Pubmed]
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