The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NCS1  -  neuronal calcium sensor 1

Homo sapiens

Synonyms: FLUP, FREQ, Frequenin homolog, Frequenin-like protein, Frequenin-like ubiquitous protein, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of FREQ


Psychiatry related information on FREQ


High impact information on FREQ

  • In intact cells, enhanced expression of NCS-1 resulted in increased intracellular calcium release upon stimulation of the phosphoinositide signaling pathway [7].
  • Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium [7].
  • We propose that NCS-1 is a novel survival-promoting factor up-regulated in injured neurons that mediates the GDNF survival signal via the phosphatidylinositol 3-kinase-Akt pathway [8].
  • In this study, we demonstrate that an EF-hand Ca2+-binding protein neuronal Ca2+ sensor-1 (NCS-1), one of the key proteins for various neuronal functions, also acts as an important survival factor [8].
  • Overexpression of NCS-1 rendered cultured neurons more tolerant to cell death caused by several kinds of stressors, whereas the dominant-negative mutant (E120Q) accelerated it [8].

Chemical compound and disease context of FREQ

  • Enzyme-linked immunoadsorbent assay revealed that NCS-1 cells expressed a 75-kDa glycoprotein which was identified as a marker of highly differentiated melanoma cells [4].

Biological context of FREQ

  • This result suggests that the interaction between variation in the DRD2 and FREQ genes, which both encode components of the D2 dopamine receptor signal transduction pathway, impacts the efficacy of NRT [5].
  • The localization of NCS-1 was unaffected by mutations in all functional EF hands, indicating that its localization was independent of Ca(2+) [9].
  • In striatum, NCS-1 and D2 receptors were found to colocalize within sites of synaptic transmission and in close proximity to intracellular calcium stores [10].
  • NCS-1-D2 receptor interaction may serve to couple dopamine and calcium signaling pathways, thereby providing a critical component in the regulation of dopaminergic signaling in normal and diseased brain [10].
  • Analysis of D2 receptors expressed in human embryonic kidney 293 cells indicates that NCS-1 attenuates agonist-induced receptor internalization via a mechanism that involves a reduction in D2 receptor phosphorylation [10].

Anatomical context of FREQ


Associations of FREQ with chemical compounds


Physical interactions of FREQ

  • These results together indicate that NCS-1 is able to interact with PI4Kbeta also in mammalian cells and may play a role in the regulation of this enzyme in specific cellular compartments affecting vesicular trafficking [13].
  • CPZ binds myristoylated as well as non-myristoylated NCS-1 in Ca(2+)-dependent manner, with dynamic interaction to myristoylated protein [16].

Other interactions of FREQ

  • Upon the elevation of intracellular Ca(2+), hippocalcin rapidly translocated to the same perinuclear compartment as NCS-1 [9].
  • Similarly, in vitro translated NCS-1, but not its myristoylation-defective mutant, was found associated with recombinant- or in vitro translated PI4Kbeta in PI4Kbeta-immunoprecipitates [13].
  • Furthermore, schizophrenia-associated alterations in the levels of calcyon and NCS-1 messages were correlated [17].
  • Mutant NCS-1 does not inhibit surface-expression of TRPC5 but generally suppresses channel activity, irrespective of whether it is evoked by carbachol, store depletion, lanthanides or elevated intracellular calcium [18].

Analytical, diagnostic and therapeutic context of FREQ

  • Allele-specific PCR studies of selected subjects indicated the existence of the CYP2D6B allele (freq = 0.17; C.I.95% = 0.085, 0.29; n = 30 unrelated subjects), in addition to the wild-type [19].
  • DMB parameters (mean DMB, DMB Freq. Max. and Heterogeneity Index of the individual distributions of DMB) were measured using quantitative microradiography in cortical, cancellous, and total bone and expressed as g mineral/cm(3) bone [20].
  • A clear cell sarcoma (CCS) cell line, designated as NCS-1, was established in monolayer culture from a xenograft line originating from a metastatic CCS [4].
  • Recently, a linear, analytical distributed model for capacitive micromachined ultrasonic transducers (CMUTs) was presented, and an electromechanical equivalent circuit based on the theory reported was used to describe the behavior of the transducer [IEEE Trans. Ultrason. Ferroelectr. Freq. Control 49, 159-168 (2002)] [21].


  1. IL1 receptor accessory protein like, a protein involved in X-linked mental retardation, interacts with Neuronal Calcium Sensor-1 and regulates exocytosis. Bahi, N., Friocourt, G., Carrié, A., Graham, M.E., Weiss, J.L., Chafey, P., Fauchereau, F., Burgoyne, R.D., Chelly, J. Hum. Mol. Genet. (2003) [Pubmed]
  2. Paclitaxel induces calcium oscillations via an inositol 1,4,5-trisphosphate receptor and neuronal calcium sensor 1-dependent mechanism. Boehmerle, W., Splittgerber, U., Lazarus, M.B., McKenzie, K.M., Johnston, D.G., Austin, D.J., Ehrlich, B.E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Preoperative staging of rectal cancer using a 7.5 MHz front-loading US probe. Akahoshi, K., Kondoh, A., Nagaie, T., Koyanagi, N., Nakanishi, K., Harada, N., Nawata, H. Gastrointest. Endosc. (2000) [Pubmed]
  4. Establishment and characterization of a clear-cell sarcoma (malignant melanoma of soft parts) cell line. Takenouchi, T., Ito, K., Kazama, T., Ito, M. Arch. Dermatol. Res. (1994) [Pubmed]
  5. Interaction between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in predicting response to nicotine replacement therapy for tobacco dependence. Dahl, J.P., Jepson, C., Levenson, R., Wileyto, E.P., Patterson, F., Berrettini, W.H., Lerman, C. Pharmacogenomics J. (2006) [Pubmed]
  6. Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients. Koh, P.O., Undie, A.S., Kabbani, N., Levenson, R., Goldman-Rakic, P.S., Lidow, M.S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium. Schlecker, C., Boehmerle, W., Jeromin, A., DeGray, B., Varshney, A., Sharma, Y., Szigeti-Buck, K., Ehrlich, B.E. J. Clin. Invest. (2006) [Pubmed]
  8. Novel role of neuronal Ca2+ sensor-1 as a survival factor up-regulated in injured neurons. Nakamura, T.Y., Jeromin, A., Smith, G., Kurushima, H., Koga, H., Nakabeppu, Y., Wakabayashi, S., Nabekura, J. J. Cell Biol. (2006) [Pubmed]
  9. Differential use of myristoyl groups on neuronal calcium sensor proteins as a determinant of spatio-temporal aspects of Ca2+ signal transduction. O'Callaghan, D.W., Ivings, L., Weiss, J.L., Ashby, M.C., Tepikin, A.V., Burgoyne, R.D. J. Biol. Chem. (2002) [Pubmed]
  10. Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. Kabbani, N., Negyessy, L., Lin, R., Goldman-Rakic, P., Levenson, R. J. Neurosci. (2002) [Pubmed]
  11. Effective association of Kv channel-interacting proteins with Kv4 channel is mediated with their unique core peptide. Ren, X., Shand, S.H., Takimoto, K. J. Biol. Chem. (2003) [Pubmed]
  12. Human neuronal calcium sensor-1 shows the highest expression level in cerebral cortex. Chen, C., Yu, L., Zhang, P., Jiang, J., Zhang, Y., Chen, X., Wu, Q., Wu, Q., Zhao, S. Neurosci. Lett. (2002) [Pubmed]
  13. Interaction of neuronal calcium sensor-1 (NCS-1) with phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and affects membrane trafficking in COS-7 cells. Zhao, X., Várnai, P., Tuymetova, G., Balla, A., Tóth, Z.E., Oker-Blom, C., Roder, J., Jeromin, A., Balla, T. J. Biol. Chem. (2001) [Pubmed]
  14. Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta stimulate extracellular signal-regulated kinase 1/2 signaling by accelerating recycling through the endocytic recycling compartment. Kapp-Barnea, Y., Ninio-Many, L., Hirschberg, K., Fukuda, M., Jeromin, A., Sagi-Eisenberg, R. Mol. Biol. Cell (2006) [Pubmed]
  15. Neuronal calcium sensor-1 and phosphatidylinositol 4-kinase beta regulate IgE receptor-triggered exocytosis in cultured mast cells. Kapp-Barnea, Y., Melnikov, S., Shefler, I., Jeromin, A., Sagi-Eisenberg, R. J. Immunol. (2003) [Pubmed]
  16. Calcium and chlorpromazine binding to the EF-hand peptides of neuronal calcium sensor-1. Muralidhar, D., Kunjachen Jobby, M., Jeromin, A., Roder, J., Thomas, F., Sharma, Y. Peptides (2004) [Pubmed]
  17. Abnormalities in the dopamine system in schizophrenia may lie in altered levels of dopamine receptor-interacting proteins. Bai, J., He, F., Novikova, S.I., Undie, A.S., Dracheva, S., Haroutunian, V., Lidow, M.S. Biol. Psychiatry (2004) [Pubmed]
  18. Calcium-sensing mechanism in TRPC5 channels contributing to retardation of neurite outgrowth. Hui, H., McHugh, D., Hannan, M., Zeng, F., Xu, S.Z., Khan, S.U., Levenson, R., Beech, D.J., Weiss, J.L. J. Physiol. (Lond.) (2006) [Pubmed]
  19. Evolutionary pharmacogenetics of CYP2D6 in Ngawbe Guaymi of Panama: allele-specific PCR detection of the CYP2D6B allele and RFLP analysis. Jorge, L.F., Arias, T.D., Griese, U., Nebert, D.W., Eichelbaum, M. Pharmacogenetics (1993) [Pubmed]
  20. Influence of estrogen therapy at conventional and high doses on the degree of mineralization of iliac bone tissue: a quantitative microradiographic analysis in postmenopausal women. Boivin, G., Vedi, S., Purdie, D.W., Compston, J.E., Meunier, P.J. Bone (2005) [Pubmed]
  21. Electromechanical coupling factor of capacitive micromachined ultrasonic transducers. Caronti, A., Carotenuto, R., Pappalardo, M. The Journal of the Acoustical Society of America. (2003) [Pubmed]
WikiGenes - Universities