Summary: A neuronal calcium sensor protein that is expressed as several isoforms and can interact with ACTIN; TUBULIN; and CLATHRIN.

Top Publications

  1. Bernstein H, Becker A, Keilhoff G, Spilker C, Gorczyca W, Braunewell K, et al. Brain region-specific changes in the expression of calcium sensor proteins after repeated applications of ketamine to rats. Neurosci Lett. 2003;339:95-8 pubmed
    ..G., Braunewell, K.-H., Spilker, C., Danos, P., Baumann, B., Funke, S., Diekmann, S., Gundelfinger, E.D. and Bogerts, B., NeuroReport, 13 (2002) 393-396]. ..
  2. Ladant D. Calcium and membrane binding properties of bovine neurocalcin delta expressed in Escherichia coli. J Biol Chem. 1995;270:3179-85 pubmed
    ..I have examined the calcium and membrane binding properties of recombinant myristoylated and unmyristoylated neurocalcin delta...
  3. Krishnan A, Venkataraman V, Fik Rymarkiewicz E, Duda T, Sharma R. Structural, biochemical, and functional characterization of the calcium sensor neurocalcin delta in the inner retinal neurons and its linkage with the rod outer segment membrane guanylate cyclase transduction system. Biochemistry. 2004;43:2708-23 pubmed the previously characterized ROS-GC1 from the photoreceptor outer segments (PROS), and its new modulator is neurocalcin delta...
  4. Haynes L, Fitzgerald D, Wareing B, O Callaghan D, Morgan A, Burgoyne R. Analysis of the interacting partners of the neuronal calcium-binding proteins L-CaBP1, hippocalcin, NCS-1 and neurocalcin delta. Proteomics. 2006;6:1822-32 pubmed
    ..Three proteins of the neuronal calcium sensor (NCS) family, hippocalcin, NCS-1 and neurocalcin delta were prepared as N-terminally tagged GST fusion proteins, and the less closely related protein L-CaBP1 ..
  5. Zhao C, Noack C, Brackmann M, Gloveli T, Maelicke A, Heinemann U, et al. Neuronal Ca2+ sensor VILIP-1 leads to the upregulation of functional alpha4beta2 nicotinic acetylcholine receptors in hippocampal neurons. Mol Cell Neurosci. 2009;40:280-92 pubmed publisher
  6. Braunewell K, Klein Szanto A, Szanto A. Visinin-like proteins (VSNLs): interaction partners and emerging functions in signal transduction of a subfamily of neuronal Ca2+ -sensor proteins. Cell Tissue Res. 2009;335:301-16 pubmed publisher
    ..protein (VSNL) subfamily, including VILIP-1 (the founder protein), VILIP-2, VILIP-3, hippocalcin, and neurocalcin delta, constitute a highly homologous subfamily of neuronal calcium sensor (NCS) proteins...
  7. Dai F, Zhang Y, Kang Y, Wang Q, Gaisano H, Braunewell K, et al. The neuronal Ca2+ sensor protein visinin-like protein-1 is expressed in pancreatic islets and regulates insulin secretion. J Biol Chem. 2006;281:21942-53 pubmed
    ..Increased VILIP-1 enhanced insulin secretion in a cAMP-associated manner. Down-regulation of VILIP-1 was accompanied by decreased cAMP accumulation but increased insulin gene transcription. ..
  8. Fu J, Fong K, Bellacosa A, Ross E, Apostolou S, Bassi D, et al. VILIP-1 downregulation in non-small cell lung carcinomas: mechanisms and prediction of survival. PLoS ONE. 2008;3:e1698 pubmed publisher
  9. Lin L, Braunewell K, Gundelfinger E, Anand R. Functional analysis of calcium-binding EF-hand motifs of visinin-like protein-1. Biochem Biophys Res Commun. 2002;296:827-32 pubmed

More Information


  1. Brackmann M, Schuchmann S, Anand R, Braunewell K. Neuronal Ca2+ sensor protein VILIP-1 affects cGMP signalling of guanylyl cyclase B by regulating clathrin-dependent receptor recycling in hippocampal neurons. J Cell Sci. 2005;118:2495-505 pubmed
    ..g. by influencing cGMP-signalling. ..
  2. Wang W, Zhou Z, Zhao W, Huang Y, Tang R, Ying K, et al. Molecular cloning, mapping and characterization of the human neurocalcin delta gene (NCALD). Biochim Biophys Acta. 2001;1518:162-7 pubmed
    We identified a new human gene that encodes a cognate of the bovine neurocalcin delta from a human fetal brain cDNA library; hence we named it human neurocalcin delta (NCALD) gene...
  3. Vijay Kumar S, Kumar V. Crystal structure of recombinant bovine neurocalcin. Nat Struct Biol. 1999;6:80-8 pubmed
    The crystal structure of calcium-bound unmyristoylated bovine neurocalcin from Escherichia coli has been determined at 2.4 A resolution...
  4. Kato M, Watanabe Y, Iino S, Takaoka Y, Kobayashi S, Haga T, et al. Cloning and expression of a cDNA encoding a new neurocalcin isoform (neurocalcin alpha) from bovine brain. Biochem J. 1998;331 ( Pt 3):871-6 pubmed
    b>Neurocalcin (NC), a neuron-specific EF-hand Ca2+-binding protein, purified from bovine brain [Terasawa, Nakano, Kobayashi and Hidaka (1992) J. Biol. Chem. 267, 19596-19599] contains multiple isoforms...
  5. Braunewell K, Gundelfinger E. Low level expression of calcium-sensor protein VILIP induces cAMP-dependent differentiation in rat C6 glioma cells. Neurosci Lett. 1997;234:139-42 pubmed
    ..These results suggest that depending on myristoylation, low level ectopic expression of VILIP affects basal cAMP homeostasis differentially, thereby influencing differentiation of C6 model cells. ..
  6. Okazaki K, Obata N, Inoue S, Hidaka H. S100 beta is a target protein of neurocalcin delta, an abundant isoform in glial cells. Biochem J. 1995;306 ( Pt 2):551-5 pubmed
    To clarify the function of neurocalcin delta, an isoform found abundantly in glial cells, we attempted to find its target proteins by using neurocalcin delta-affinity chromatography and the 125I-neurocalcin delta gel-overlay method...
  7. Wickborn C, Klein Szanto A, Schlag P, Braunewell K. Correlation of visinin-like-protein-1 expression with clinicopathological features in squamous cell carcinoma of the esophagus. Mol Carcinog. 2006;45:572-81 pubmed
    ..The protein expression level significantly correlates with invasive features, such as depth of tumor invasion and local lymph node metastasis, but not with proliferation rate of tumor cells. ..
  8. Faurobert E, Chen C, Hurley J, Teng D. Drosophila neurocalcin, a fatty acylated, Ca2+-binding protein that associates with membranes and inhibits in vitro phosphorylation of bovine rhodopsin. J Biol Chem. 1996;271:10256-62 pubmed
    ..Previously, we reported the cloning and initial characterization of neurocalcin in Drosophila melanogaster (Teng, D. H.-F., Chen, C.-K., and Hurley, J. B. (1994) J. Biol. Chem...
  9. Braunewell K, Brackmann M, Schaupp M, Spilker C, Anand R, Gundelfinger E. Intracellular neuronal calcium sensor (NCS) protein VILIP-1 modulates cGMP signalling pathways in transfected neural cells and cerebellar granule neurones. J Neurochem. 2001;78:1277-86 pubmed
    ..Together with the observed colocalization of GC-B, but not GC-A, with VILIP-1 in cerebellar granule cells, these results suggest that VILIP-1 may be a physiological regulator of GC-B. ..
  10. Long P, Veney S. Neurocalcin protein labeling reveals a dimorphism within the developing zebra finch brain. Brain Res. 2010;1315:11-8 pubmed publisher
    ..One product that may play a role is the calcium binding protein, neurocalcin. A previous study indicated that neurocalcin mRNA was widely distributed throughout the zebra finch ..
  11. Li C, Pan W, Braunewell K, Ames J. Structural analysis of Mg2+ and Ca2+ binding, myristoylation, and dimerization of the neuronal calcium sensor and visinin-like protein 1 (VILIP-1). J Biol Chem. 2011;286:6354-66 pubmed publisher
    ..We present the structure of the VILIP-1 dimer and a Ca(2+)-myristoyl switch to provide structural insights into Ca(2+)-induced trafficking of nicotinic acetylcholine receptors. ..
  12. Mahloogi H, Gonzalez Guerrico A, Lopez De Cicco R, Bassi D, Goodrow T, Braunewell K, et al. Overexpression of the calcium sensor visinin-like protein-1 leads to a cAMP-mediated decrease of in vivo and in vitro growth and invasiveness of squamous cell carcinoma cells. Cancer Res. 2003;63:4997-5004 pubmed
    ..These results indicate that VILIP-1 plays an important role in regulating tumor cell invasiveness and that its loss could aid in enhancing the advanced malignant phenotype. ..
  13. Terasawa M, Nakano A, Kobayashi R, Hidaka H. Neurocalcin: a novel calcium-binding protein from bovine brain. J Biol Chem. 1992;267:19596-9 pubmed
    A novel calcium-binding protein (molecular weight 23,000-24,000, pI 5.3-5.5), which we term neurocalcin, was identified in bovine brain...
  14. Venkataraman V, Duda T, Ravichandran S, Sharma R. Neurocalcin delta modulation of ROS-GC1, a new model of Ca(2+) signaling. Biochemistry. 2008;47:6590-601 pubmed publisher
    ..b>Neurocalcin delta is a CD-GCAP...
  15. Okazaki K, Watanabe M, Ando Y, Hagiwara M, Terasawa M, Hidaka H. Full sequence of neurocalcin, a novel calcium-binding protein abundant in central nervous system. Biochem Biophys Res Commun. 1992;185:147-53 pubmed
    We determined the cDNA sequence for neurocalcin, a novel calcium-binding protein in bovine brain...
  16. Gierke P, Zhao C, Bernstein H, Noack C, Anand R, Heinemann U, et al. Implication of neuronal Ca2+ -sensor protein VILIP-1 in the glutamate hypothesis of schizophrenia. Neurobiol Dis. 2008;32:162-75 pubmed publisher
  17. Gonzalez Guerrico A, Jaffer Z, Page R, Braunewell K, Chernoff J, Klein Szanto A. Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in squamous carcinoma cells. Oncogene. 2005;24:2307-16 pubmed
    ..Decreased or absent VILIP-1 expression in SCC cell subpopulations may lead to a more advanced malignant phenotype characterized by changes in adhesive ability and increased cell motility, suggestive of a tumor suppressor function. ..
  18. Braunewell K, Brackmann M, Manahan Vaughan D. Group I mGlu receptors regulate the expression of the neuronal calcium sensor protein VILIP-1 in vitro and in vivo: implications for mGlu receptor-dependent hippocampal plasticity?. Neuropharmacology. 2003;44:707-15 pubmed
    ..A specific role for group I mGlu receptors is evident. Furthermore, the sensor proteins may function as molecular switches for the long-term regulation of synaptic plasticity. ..
  19. Lin L, Jeanclos E, Treuil M, Braunewell K, Gundelfinger E, Anand R. The calcium sensor protein visinin-like protein-1 modulates the surface expression and agonist sensitivity of the alpha 4beta 2 nicotinic acetylcholine receptor. J Biol Chem. 2002;277:41872-8 pubmed
    ..Collectively, these results suggest that VILIP-1 represents a novel modulator of alpha4beta2 AChRs that increases their surface expression levels and agonist sensitivity in response to changes in the intracellular levels of calcium. ..
  20. Corns R, Hidaka H, Santer R. Neurocalcin-alpha immunoreactivity in the enteric nervous system of young and aged rats. Cell Calcium. 2002;31:53-8 pubmed
    The distribution of the calcium binding protein neurocalcin a has been examined in the enteric nervous system of young adult (3 months) and aged (24+ months) male rats by immunofluorescence...
  21. Ivings L, Pennington S, Jenkins R, Weiss J, Burgoyne R. Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin. Biochem J. 2002;363:599-608 pubmed
    ..One of the family members is neurocalcin delta, the function of which is unknown...
  22. Murias A, Weruaga E, Recio J, Airado C, Diaz D, Alonso J. Distribution of neurocalcin-containing neurons reveals sexual dimorphism in the mouse olfactory bulb. Chem Senses. 2007;32:673-80 pubmed
    ..There are no data indicating sex-related differences in the neurochemistry of intrinsic olfactory elements. Neurocalcin (NC) is a calcium-binding protein that is expressed in specific neuronal populations of the central nervous ..
  23. Braunewell K, Spilker C, Behnisch T, Gundelfinger E. The neuronal calcium-sensor protein VILIP modulates cyclic AMP accumulation in stably transfected C6 glioma cells: amino-terminal myristoylation determines functional activity. J Neurochem. 1997;68:2129-39 pubmed
    ..These results suggest that VILIP acts as a calcium sensor molecule that modulates cell signaling cascades, possibly by direct or indirect regulation of adenylyl cyclase activity. ..
  24. Lee J, Blennow K, Andreasen N, Laterza O, Modur V, Olander J, et al. The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clin Chem. 2008;54:1617-23 pubmed publisher
    ..635) but not Abeta(1-42) (r = -0.233). VLP-1 was the only biomarker that correlated with MMSE score (r = -0.384, P = 0.030). These results suggest that neuronal injury markers such as VLP-1 may have utility as biomarkers for AD. ..
  25. Chen K, Wang L, Chang L. Regulatory elements and functional implication for the formation of dimeric visinin-like protein-1. J Pept Sci. 2009;15:89-94 pubmed publisher
    ..Together with disulfide dimer of VILIP-1 detected in rat brain extracts, our data may imply the functional contribution of disulfide dimer to the interaction of VILIP-1 with its physiological target(s). ..
  26. Hidaka H, Okazaki K. Neurocalcin family: a novel calcium-binding protein abundant in bovine central nervous system. Neurosci Res. 1993;16:73-7 pubmed
    We purified and sequenced from bovine brain a novel calcium-binding protein. This protein which we named neurocalcin has 3 putative EF hand motifs and a close homology with recoverin which activates guanylate cyclase Ca2+ dependently...
  27. Iino S, Kobayashi S, Hidaka H. Neurocalcin-immunopositive nerve terminals in the muscle spindle, Golgi tendon organ and motor endplate. Brain Res. 1998;808:294-9 pubmed
    The present study revealed the immunohistochemical distribution of neurocalcin, a three EF-hand calcium-binding protein, in the rat muscles and tendons...
  28. Beveridge N, Tooney P, Carroll A, Gardiner E, Bowden N, Scott R, et al. Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet. 2008;17:1156-68 pubmed publisher
    ..This study suggests altered miRNA levels could be a significant factor in the dysregulation of cortical gene expression in schizophrenia. ..
  29. Kamiyama M, Kobayashi M, Araki S, Iida A, Tsunoda T, Kawai K, et al. Polymorphisms in the 3' UTR in the neurocalcin delta gene affect mRNA stability, and confer susceptibility to diabetic nephropathy. Hum Genet. 2007;122:397-407 pubmed
    ..single nucleotide polymorphisms (SNPs) in Japanese type 2 diabetic patients, we have identified a gene encoding neurocalcin delta (NCALD) as a candidate for a susceptibility gene to diabetic nephropathy; the landmark SNP was found in ..
  30. Spilker C, Dresbach T, Braunewell K. Reversible translocation and activity-dependent localization of the calcium-myristoyl switch protein VILIP-1 to different membrane compartments in living hippocampal neurons. J Neurosci. 2002;22:7331-9 pubmed
  31. Mathisen P, Johnson J, Kawczak J, Tuohy V. Visinin-like protein (VILIP) is a neuron-specific calcium-dependent double-stranded RNA-binding protein. J Biol Chem. 1999;274:31571-6 pubmed
    ..Given that VILIP is also expressed in the hippocampus, these data suggest that VILIP may employ a novel, calcium-dependent mechanism to regulate its binding to important localized mRNAs in the central nervous system. ..
  32. Spilker C, Braunewell K. Calcium-myristoyl switch, subcellular localization, and calcium-dependent translocation of the neuronal calcium sensor protein VILIP-3, and comparison with VILIP-1 in hippocampal neurons. Mol Cell Neurosci. 2003;24:766-78 pubmed
    ..Thus, VILIPs co-expressed in the same neuron show clear differences in calcium-dependent localization which may allow neurons a highly selective response to various calcium stimuli. ..
  33. Germana A, del Valle M, Laura R, Ciriaco E, Vega J, Germana G. Effects of neurotrophin-3 gene mutation in the expression of neurocalcin. Ital J Anat Embryol. 2005;110:37-47 pubmed
    b>Neurocalcin (NC) is a neuron-specific "EF-hand" calcium-binding protein present in a non-fully characterized subpopulation of dorsal root ganglion (DRG) neurons, some kinds of mechanoreceptors and proprioceptors, and in motor ..
  34. Ola R, Lefebvre S, Braunewell K, Sainio K, Sariola H. The expression of Visinin-like 1 during mouse embryonic development. Gene Expr Patterns. 2012;12:53-62 pubmed publisher
    ..g. taste buds, cochlea, thyroid, tooth, salivary and adrenal gland. The stage specific expression pattern of Vsnl1 makes it a potentially useful marker particularly in studies of cardiac and vascular morphogenesis. ..
  35. Kajimoto Y, Shirai Y, Mukai H, Kuno T, Tanaka C. Molecular cloning of two additional members of the neural visinin-like Ca(2+)-binding protein gene family. J Neurochem. 1993;61:1091-6 pubmed
    ..These results suggest that NVP-2 and NVP-3 are additional members of the NVP gene family. ..
  36. Braunewell K, Riederer P, Spilker C, Gundelfinger E, Bogerts B, Bernstein H. Abnormal localization of two neuronal calcium sensor proteins, visinin-like proteins (vilips)-1 and -3, in neocortical brain areas of Alzheimer disease patients. Dement Geriatr Cogn Disord. 2001;12:110-6 pubmed
    ..Our morphological and neurochemical findings point to an involvement of these two neuronal calcium sensor proteins in pathology and possibly pathophysiology of changed calcium homeostasis in AD. ..
  37. Masutani T, Taguchi K, Kumanogoh H, Nakamura S, Maekawa S. Molecular interaction of neurocalcin alpha with alsin (ALS2). Neurosci Lett. 2008;438:26-8 pubmed publisher
    ..b>Neurocalcin alpha (NCalpha) is a member of neuronal calcium sensor (NCS) protein family and shows Ca(2+)-dependent binding ..
  38. Spilker C, Gundelfinger E, Braunewell K. Evidence for different functional properties of the neuronal calcium sensor proteins VILIP-1 and VILIP-3: from subcellular localization to cellular function. Biochim Biophys Acta. 2002;1600:118-27 pubmed
  39. Laterza O, Modur V, Crimmins D, Olander J, Landt Y, Lee J, et al. Identification of novel brain biomarkers. Clin Chem. 2006;52:1713-21 pubmed
    ..One of the biomarkers identified, VLP-1, was increased in a rat model of stroke and in plasma of patients after stroke. More extensive, prospective studies of the candidate biomarkers identified appear warranted. ..
  40. Verbeek M, Olde Rikkert M. Cerebrospinal fluid biomarkers in the evaluation of Alzheimer disease. Clin Chem. 2008;54:1589-91 pubmed publisher
  41. Findeisen P, Röckel M, Nees M, Roder C, Kienle P, von Knebel Doeberitz M, et al. Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients. Int J Oncol. 2008;33:1001-10 pubmed
    ..In conclusion SERPINB5 seems to be a promising marker for detection of circulating tumor cells in peripheral blood of colorectal cancer patients. ..
  42. Iino S, Kobayashi S, Hidaka H. Heterogeneous distribution of neurocalcin-immunoreactive nerve terminals in the mouse adrenal medulla. Cell Tissue Res. 1997;289:439-44 pubmed
    b>Neurocalcin is a novel calcium-binding protein found in bovine brain tissue. We investigated immunoreactivity for neurocalcin in the mouse adrenal medulla using light and electron microscopy...
  43. Ohya S, Horowitz B. Differential transcriptional expression of Ca2+ BP superfamilies in murine gastrointestinal smooth muscles. Am J Physiol Gastrointest Liver Physiol. 2002;283:G1290-7 pubmed
    ..On the other hand, of seven CaBPs including alternatively spliced variants, only CaBP1L transcripts were detected in GISMs. ..
  44. Winterer G. Why do patients with schizophrenia smoke?. Curr Opin Psychiatry. 2010;23:112-9 pubmed publisher
    ..Heavy smoking in schizophrenia cannot simply be viewed as a 'bad habit'. Rather, self-medication of clinical symptoms and side effects of antipsychotic drugs appear to play a major role. ..
  45. Stejskal D, Sporova L, Svestak M, Karpisek M. Determination of serum visinin like protein-1 and its potential for the diagnosis of brain injury due to the stroke: a pilot study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011;155:263-8 pubmed publisher
    ..Our results support the hypothesis that serum VILIP-1 may be associated with ischemic stroke. The ELISA VILIP-1 assay offers a new research tool for the diagnosis and pathophysiology of stroke and other CNS diseases. ..
  46. Liu M, Yang H, Fang D, Yang J, Cai J, Wan Y, et al. Upregulation of P2X3 receptors by neuronal calcium sensor protein VILIP-1 in dorsal root ganglions contributes to the bone cancer pain in rats. Pain. 2013;154:1551-68 pubmed publisher
    ..Pharmacological blockade of P2X3 receptors or knockdown of VILIP-1 in DRGs would be used as innovative strategies for the treatment of bone cancer pain. ..
  47. Martinez Guijarro F, Briñón J, Blasco Ibáñez J, Okazaki K, Hidaka H, Alonso J. Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons. Hippocampus. 1998;8:2-23 pubmed
    b>Neurocalcin (NC) is a recently described calcium-binding protein isolated and characterized from bovine brain...
  48. McFerran B, Graham M, Burgoyne R. Neuronal Ca2+ sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin and PC12 cells and regulates neurosecretion from dense-core granules. J Biol Chem. 1998;273:22768-72 pubmed
    ..No effect of overexpression was seen on GH release because of Ca2+ in permeabilized cells suggesting that NCS-1 may have a regulatory but not direct role in neurosecretion. ..
  49. Duda T, Sharma R. ONE-GC membrane guanylate cyclase, a trimodal odorant signal transducer. Biochem Biophys Res Commun. 2008;367:440-5 pubmed publisher
    ..Its intracellular region contains Ca(2+) sensor recognition domains linked to GCAP1 and to neurocalcin delta, and a catalytic module. These domains sense increments in free Ca(2+) and stimulate the catalytic module...
  50. Xie Y, Chan H, Fan J, Chen Y, Young J, Li W, et al. Involvement of visinin-like protein-1 (VSNL-1) in regulating proliferative and invasive properties of neuroblastoma. Carcinogenesis. 2007;28:2122-30 pubmed
    ..These results suggested that distinct roles of proliferative and invasive phenotypes contributed to neuroblastoma progression and strongly demonstrated that VSNL-1 played a very important role in neuroblastoma metastasis. ..
  51. Jheng F, Wang L, Lee L, Chang L. Functional contribution of Ca2+ and Mg2+ to the intermolecular interaction of visinin-like proteins. Protein J. 2006;25:250-6 pubmed
  52. Beven L, Adenier H, Kichenama R, Homand J, Redeker V, Le Caer J, et al. Ca2+-myristoyl switch and membrane binding of chemically acylated neurocalcins. Biochemistry. 2001;40:8152-60 pubmed
    b>Neurocalcin is a member of a novel family of neuronal calcium sensors that belongs to the superfamily of EF-hand Ca(2+)-binding proteins...
  53. Duda T, Fik Rymarkiewicz E, Venkataraman V, Krishnan A, Sharma R. Calcium-modulated ciliary membrane guanylate cyclase transduction machinery: constitution and operational principles. Mol Cell Biochem. 2004;267:107-22 pubmed
    ..Myristoylated (myr)-neurocalcin delta is the Ca2+ -sensor component and the cyclase, ONE-GC, the transduction component of the machinery...