Summary: A neuronal calcium-sensor protein that was initially found in the NEURONS of the HIPPOCAMPUS. It interacts with NEURONAL APOPTOSIS-INHIBITORY PROTEIN.

Top Publications

  1. Kobayashi M, Takamatsu K, Saitoh S, Miura M, Noguchi T. Molecular cloning of hippocalcin, a novel calcium-binding protein of the recoverin family exclusively expressed in hippocampus. Biochem Biophys Res Commun. 1992;189:511-7 pubmed
    ..Northern blot, in situ hybridization, immunoblot and immunohistochemical analyses revealed that the protein is exclusively expressed in pyramidal layer of the hippocampus. The protein was therefore designated hippocalcin.
  2. Tzingounis A, Nicoll R. Contribution of KCNQ2 and KCNQ3 to the medium and slow afterhyperpolarization currents. Proc Natl Acad Sci U S A. 2008;105:19974-9 pubmed publisher
    ..We also present data suggesting that the neuronal calcium sensor protein hippocalcin may allow for these dual signaling processes.
  3. Koh P. Melatonin regulates the calcium-buffering proteins, parvalbumin and hippocalcin, in ischemic brain injury. J Pineal Res. 2012;53:358-65 pubmed publisher
    ..Calcium-buffering proteins including parvalbumin and hippocalcin are involved in neuronal differentiation and maturation through calcium signaling...
  4. Korhonen L, Hansson I, Kukkonen J, Brännvall K, Kobayashi M, Takamatsu K, et al. Hippocalcin protects against caspase-12-induced and age-dependent neuronal degeneration. Mol Cell Neurosci. 2005;28:85-95 pubmed
    b>Hippocalcin is a neuronal calcium binding protein, but its physiological function in brain is unknown...
  5. O Callaghan D, Tepikin A, Burgoyne R. Dynamics and calcium sensitivity of the Ca2+/myristoyl switch protein hippocalcin in living cells. J Cell Biol. 2003;163:715-21 pubmed
    b>Hippocalcin is a neuronal calcium sensor protein that possesses a Ca2+/myristoyl switch allowing it to translocate to membranes...
  6. Rudinskiy N, Kaneko Y, Beesen A, Gokce O, Regulier E, Déglon N, et al. Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons. J Neurochem. 2009;111:460-72 pubmed publisher
    b>Hippocalcin is a neuronal calcium sensor protein previously implicated in regulating neuronal viability and plasticity...
  7. 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. ..
  8. Jo J, Son G, Winters B, Kim M, Whitcomb D, Dickinson B, et al. Muscarinic receptors induce LTD of NMDAR EPSCs via a mechanism involving hippocalcin, AP2 and PSD-95. Nat Neurosci. 2010;13:1216-24 pubmed publisher
    ..suggest that the molecular mechanism involves a dynamic interaction between the neuronal calcium sensor protein hippocalcin, the clathrin adaptor molecule AP2, the postsynaptic density enriched protein PSD-95 and NMDARs...
  9. Kim K, Kobayashi M, Takamatsu K, Tzingounis A. Hippocalcin and KCNQ channels contribute to the kinetics of the slow afterhyperpolarization. Biophys J. 2012;103:2446-54 pubmed publisher
    ..Here, we test whether KCNQ channels shape the sAHP rise and decay kinetics in wild-type mice and mice lacking Hippocalcin, the putative sAHP calcium sensor...

More Information


  1. Kobayashi M, Takamatsu K, Fujishiro M, Saitoh S, Noguchi T. Molecular cloning of a novel calcium-binding protein structurally related to hippocalcin from human brain and chromosomal mapping of its gene. Biochim Biophys Acta. 1994;1222:515-8 pubmed
    A cDNA clone (hHLP2) encoding a novel calcium-binding protein structurally related to hippocalcin has been isolated from the human hippocampus cDNA library...
  2. Kobayashi M, Takamatsu K, Saitoh S, Miura M, Noguchi T. Molecular cloning of hippocalcin, a novel calcium-binding protein of the recoverin family exclusively expressed in hippocampus. Biochem Biophys Res Commun. 1993;196:1017 pubmed
  3. 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 ..
  4. Krishnan A, Duda T, Pertzev A, Kobayashi M, Takamatsu K, Sharma R. Hippocalcin, new Ca(2+) sensor of a ROS-GC subfamily member, ONE-GC, membrane guanylate cyclase transduction system. Mol Cell Biochem. 2009;325:1-14 pubmed publisher
    b>Hippocalcin is a member of the neuronal Ca(2+) sensor protein family...
  5. O Callaghan D, Ivings L, Weiss J, Ashby M, Tepikin A, Burgoyne R. Differential use of myristoyl groups on neuronal calcium sensor proteins as a determinant of spatio-temporal aspects of Ca2+ signal transduction. J Biol Chem. 2002;277:14227-37 pubmed
    The localizations of three members of the neuronal calcium sensor (NCS) family were studied in HeLa cells. Using hippocalcin-EYFP and NCS-1-ECFP, it was found that their localization differed dramatically in resting cells...
  6. Burgoyne R, Weiss J. The neuronal calcium sensor family of Ca2+-binding proteins. Biochem J. 2001;353:1-12 pubmed
    ..In the present review we describe the known sequences and structures of the NCS proteins, information on their interactions with target proteins and current knowledge about their cellular and physiological functions. ..
  7. Mercer E, Korhonen L, Skoglösa Y, Olsson P, Kukkonen J, Lindholm D. NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways. EMBO J. 2000;19:3597-607 pubmed
    ..its third baculovirus inhibitory repeat domain (BIR3), binds the neuron-restricted calcium-binding protein, hippocalcin, in an interaction promoted by calcium...
  8. Palmer C, Lim W, Hastie P, Toward M, Korolchuk V, Burbidge S, et al. Hippocalcin functions as a calcium sensor in hippocampal LTD. Neuron. 2005;47:487-94 pubmed
    ..Here we show that the neuronal Ca(2+) sensor hippocalcin binds the beta2-adaptin subunit of the AP2 adaptor complex and that along with GluR2 these coimmunoprecipitate ..
  9. Oh D, Yon C, Oh K, Lee K, Han J. Hippocalcin increases phospholipase D2 expression through extracellular signal-regulated kinase activation and lysophosphatidic acid potentiates the hippocalcin-induced phospholipase D2 expression. J Cell Biochem. 2006;97:1052-65 pubmed
    ..a rat brain which was found to be involved in activating phospholipsae D (PLD), and identified the protein as hippocalcin through sequence analysis...
  10. Kobayashi M, Takamatsu K, Saitoh S, Noguchi T. Myristoylation of hippocalcin is linked to its calcium-dependent membrane association properties. J Biol Chem. 1993;268:18898-904 pubmed
    b>Hippocalcin, a recently identified Ca(2+)-binding protein of the recoverin family exclusively expressed in the hippocampus, has a primary structure containing three putative Ca(2+)-binding sites (EF-hands) and a possible NH2-terminal ..
  11. Tzingounis A, Kobayashi M, Takamatsu K, Nicoll R. Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells. Neuron. 2007;53:487-93 pubmed
    ..Here we report that the key intermediate between calcium and the sAHP channels is the diffusible calcium sensor hippocalcin. Brief depolarizations sufficient to activate the I(sAHP) in wild-type mice do not elicit the I(sAHP) in ..
  12. Oh D, Cho J, Park S, Kim Y, Yoon Y, Yoon S, et al. A novel role of hippocalcin in bFGF-induced neurite outgrowth of H19-7 cells. J Neurosci Res. 2008;86:1557-65 pubmed publisher
    b>Hippocalcin is a Ca2+-binding protein that is expressed mainly in pyramidal nerve cells of the hippocampus. However, its functions and mechanism in the brain remain unclear...
  13. Tanaka T, Ames J, Harvey T, Stryer L, Ikura M. Sequestration of the membrane-targeting myristoyl group of recoverin in the calcium-free state. Nature. 1995;376:444-7 pubmed
    ..The myristoyl group is sequestered in a deep hydrophobic pocket formed by many aromatic and other hydrophobic residues from five flanking helices. ..
  14. Markova O, Fitzgerald D, Stepanyuk A, Dovgan A, Cherkas V, Tepikin A, et al. Hippocalcin signaling via site-specific translocation in hippocampal neurons. Neurosci Lett. 2008;442:152-7 pubmed publisher
    b>Hippocalcin is a Ca(2+)-binding protein, which belongs to the family of neuronal Ca(2+) sensors...
  15. Senin I, Fischer T, Komolov K, Zinchenko D, Philippov P, Koch K. Ca2+-myristoyl switch in the neuronal calcium sensor recoverin requires different functions of Ca2+-binding sites. J Biol Chem. 2002;277:50365-72 pubmed
    ..We discuss this mechanism as one critical step for inhibition of rhodopsin kinase by recoverin. ..
  16. Masuo Y, Ogura A, Kobayashi M, Masaki T, Furuta Y, Ono T, et al. Hippocalcin protects hippocampal neurons against excitotoxin damage by enhancing calcium extrusion. Neuroscience. 2007;145:495-504 pubmed
    b>Hippocalcin, which is a member of the neuronal calcium-sensor protein family, is highly expressed in hippocampal pyramidal cells...
  17. Dovgan A, Cherkas V, Stepanyuk A, Fitzgerald D, Haynes L, Tepikin A, et al. Decoding glutamate receptor activation by the Ca2+ sensor protein hippocalcin in rat hippocampal neurons. Eur J Neurosci. 2010;32:347-58 pubmed publisher
    b>Hippocalcin is a Ca(2+)-binding protein that belongs to a family of neuronal Ca(2+)sensors and is a key mediator of many cellular functions including synaptic plasticity and learning...
  18. O Callaghan D, Haynes L, Burgoyne R. High-affinity interaction of the N-terminal myristoylation motif of the neuronal calcium sensor protein hippocalcin with phosphatidylinositol 4,5-bisphosphate. Biochem J. 2005;391:231-8 pubmed
    ..In the case of hippocalcin and NCS-1, or alternatively KChIP1 (K+ channel-interacting protein 1), their N-terminal myristoylation motifs ..
  19. Lim Y, Giese M, Shepherd C, Halliday G, Kobayashi M, Takamatsu K, et al. Role of hippocalcin in mediating A? toxicity. Biochim Biophys Acta. 2012;1822:1247-57 pubmed publisher
    ..Interestingly, it is the latter brain area where the calcium-sensing enzyme hippocalcin is highly expressed...
  20. Lindholm D, Mercer E, Yu L, Chen Y, Kukkonen J, Korhonen L, et al. Neuronal apoptosis inhibitory protein: Structural requirements for hippocalcin binding and effects on survival of NGF-dependent sympathetic neurons. Biochim Biophys Acta. 2002;1600:138-47 pubmed
    ..Recently, NAIP was shown to interact with hippocalcin, which belongs to the neuronal calcium sensor (NCS) protein family...
  21. Kobayashi M, Masaki T, Hori K, Masuo Y, Miyamoto M, Tsubokawa H, et al. Hippocalcin-deficient mice display a defect in cAMP response element-binding protein activation associated with impaired spatial and associative memory. Neuroscience. 2005;133:471-84 pubmed
    b>Hippocalcin is a member of the neuronal calcium sensor (NCS) protein family that is highly expressed in hippocampal pyramidal cells and moderately expressed in the neurons of cerebral cortex, cerebellum and striatum...
  22. Ohguro H, Maruyama I, Nakazawa M, Oohira A. Antirecoverin antibody in the aqueous humor of a patient with cancer-associated retinopathy. Am J Ophthalmol. 2002;134:605-7 pubmed
    ..To describe a patient with cancer-associated retinopathy (CAR) in whom antirecoverin antibody was found in the aqueous humor...
  23. Nettelbeck D, Rivera A, Kupsch J, Dieckmann D, Douglas J, Kontermann R, et al. Retargeting of adenoviral infection to melanoma: combining genetic ablation of native tropism with a recombinant bispecific single-chain diabody (scDb) adapter that binds to fiber knob and HMWMAA. Int J Cancer. 2004;108:136-45 pubmed
  24. Ohguro H, Yokoi Y, Ohguro I, Mamiya K, Ishikawa F, Yamazaki H, et al. Clinical and immunologic aspects of cancer-associated retinopathy. Am J Ophthalmol. 2004;137:1117-9 pubmed
    ..For diagnosis of cancer-associated retinopathy, the presence of serum autoantibody toward recoverin is essentially required in addition to the characteristic clinical aspects noted above. ..
  25. Adamus G. Autoantibody-induced apoptosis as a possible mechanism of autoimmune retinopathy. Autoimmun Rev. 2003;2:63-8 pubmed
    ..Thus, autoantibody-induced apoptosis may be a common pathway that leads to retinal death and blindness. ..
  26. Elliott R, Miles M, Lowenstein D. Overlapping microarray profiles of dentate gyrus gene expression during development- and epilepsy-associated neurogenesis and axon outgrowth. J Neurosci. 2003;23:2218-27 pubmed
  27. Brown D, Lancaster B, Shah M. Hippocalcin: a new solution to an old puzzle. Neuron. 2007;53:467-8 pubmed
    ..In this issue of Neuron, Tzingounis et al. now show that calcium binding to hippocalcin, a member of the NCS family, is one of the necessary steps involved in production of the sAHP.
  28. Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases. Arch Ophthalmol. 1999;117:471-7 pubmed
  29. Sun L, Tu L, Lu Y. Targeting YAP acetylation in cancer. J Biol Chem. 2012;287:35442; author reply 35443 pubmed publisher
  30. Jiang S, Miao B, Song X, Jiang Z. Inactivation of GABA(A) receptor reduces ginsenoside Rb3 neuroprotection in mouse hippocampal slices after oxygen-glucose deprivation. J Ethnopharmacol. 2011;133:914-6 pubmed publisher
    ..The results indicate that the activation of the GABA(A) receptor is correlated with the neuroprotective mechanisms of ginsenoside Rb(3). ..
  31. Thirkill C, Tait R, Tyler N, Roth A, Keltner J. The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci. 1992;33:2768-72 pubmed
    ..Nucleotide sequence analysis suggests that the CAR antigen shows approximately 90% homology to the published amino acid sequence of bovine recoverin. ..
  32. Palczewski K, Subbaraya I, Gorczyca W, Helekar B, Ruiz C, Ohguro H, et al. Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase-activating protein. Neuron. 1994;13:395-404 pubmed
  33. Suzuki T, Obara Y, Sato Y, Saito G, Ichiwata T, Uchiyama T. Cancer-associated retinopathy with presumed vasculitis. Am J Ophthalmol. 1996;122:125-7 pubmed
    ..Cancer-associated retinopathy was diagnosed. The staining seen on the angiogram appears to indicate vasculitis, which would cause the characteristic attenuation of retinal vessels in this disease. ..
  34. Kawamura S, Tachibanaki S. S-modulin. Adv Exp Med Biol. 2002;514:61-8 pubmed
    ..With this mechanism, S-modulin is believed to regulate the waveform of a photoresponse and the efficiency of the light in the generation of a photoresponse. ..
  35. Ohguro H, Ogawa K, Maeda T, Maruyama I, Maeda A, Takano Y, et al. Retinal dysfunction in cancer-associated retinopathy is improved by Ca(2+) antagonist administration and dark adaptation. Invest Ophthalmol Vis Sci. 2001;42:2589-95 pubmed
  36. Philippov P. Phototransduction and calcium. Membr Cell Biol. 2000;13:195-206 pubmed
    ..This review describes the overall picture of phototransduction molecular mechanisms with special emphasis on participation of Ca2+ in visual cell signalling. ..
  37. Wiechmann A, Sinacola M. Diurnal expression of recoverin in the rat retina. Brain Res Mol Brain Res. 1997;45:321-4 pubmed
  38. Whitcup S, Vistica B, Milam A, Nussenblatt R, Gery I. Recoverin-associated retinopathy: a clinically and immunologically distinctive disease. Am J Ophthalmol. 1998;126:230-7 pubmed
    ..We propose that this immunologically and clinically distinctive condition be termed recoverin-associated retinopathy, and we suggest that a cellular immune response against recoverin may be a distinguishing feature of the disorder. ..
  39. Ohguro H, Ogawa K, Maeda T, Maeda A, Maruyama I. Cancer-associated retinopathy induced by both anti-recoverin and anti-hsc70 antibodies in vivo. Invest Ophthalmol Vis Sci. 1999;40:3160-7 pubmed
    ..These observations suggest that anti-recoverin- and anti-hsc 70 antibody-induced retinal dysfunction in Lewis rat is a good model to study the pathophysiology of CAR. ..
  40. Takamatsu K, Kobayashi M, Saitoh S, Fujishiro M, Noguchi T. Molecular cloning of human hippocalcin cDNA and chromosomal mapping of its gene. Biochem Biophys Res Commun. 1994;200:606-11 pubmed
    We have isolated a cDNA clone encoding human hippocalcin from a human hippocampus cDNA library...
  41. Kawamura S, Hisatomi O, Kayada S, Tokunaga F, Kuo C. Recoverin has S-modulin activity in frog rods. J Biol Chem. 1993;268:14579-82 pubmed
    ..Here, we show that recoverin has similar activity as S-modulin, and the amino acid sequences of both proteins are similar. The results strongly suggest that recoverin is bovine S-modulin and regulates PDE activation. ..
  42. Wiechmann A, Hammarback J. Molecular cloning and nucleotide sequence of a cDNA encoding recoverin from human retina. Exp Eye Res. 1993;56:463-70 pubmed
    ..Direct sequencing of a Y79 retinoblastoma cDNA polymerase chain reaction (PCR) product confirmed the presence of recoverin in this human cell line. ..
  43. Robey R, Zhan Z, Piekarz R, Kayastha G, Fojo T, Bates S. Increased MDR1 expression in normal and malignant peripheral blood mononuclear cells obtained from patients receiving depsipeptide (FR901228, FK228, NSC630176). Clin Cancer Res. 2006;12:1547-55 pubmed
    ..These studies suggest that depsipeptide induces its own mechanism of resistance and thus provide a basis for clinical trials evaluating depsipeptide in combination with a Pgp inhibitor...
  44. Permiakov S, Uverskiĭ V, Cherskaia A, Shul ga Morskoĭ S, Zinchenko D, Alekseev A, et al. [Point amino acid substitutions in Ca2+-binding centers of recoverin. III. Mutant with the fourth reconstructed Ca2+-binding site]. Bioorg Khim. 2000;26:285-9 pubmed
  45. Chen W, Elias R, Cao W, Lerious V, McGinnis J. Anti-recoverin antibodies cause the apoptotic death of mammalian photoreceptor cells in vitro. J Neurosci Res. 1999;57:706-18 pubmed
    ..The results suggest that anti-recoverin antibodies play a key role in the apoptotic death of photoreceptors in CAR. ..
  46. Win Shwe T, Yamamoto S, Fujitani Y, Hirano S, Fujimaki H. Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust. Neurotoxicology. 2008;29:940-7 pubmed publisher
    ..These results indicate that co-exposure of NRDE and LTA could affect spatial learning and memory function-related gene expressions in mouse hippocampus. ..
  47. Permiakov S, Senin I, Uverskiĭ V, Cherskaia A, Shul ga Morskoĭ S, Zinchenko D, et al. [Point amino acid substitutions in the Ca2+-binding centers of recoverin. I. Mechanism of successive filling of Ca2+-binding centers]. Bioorg Khim. 1999;25:742-6 pubmed
    ..The binding constants for the third and the second Ca(2+)-binding sites of recoverin determined by spectrofluorimetric titration are 3.7 x 10(6) and 3.1 x 10(5) M-1, respectively. ..
  48. Hahn P, Lindsten T, Ying G, Bennett J, Milam A, Thompson C, et al. Proapoptotic bcl-2 family members, Bax and Bak, are essential for developmental photoreceptor apoptosis. Invest Ophthalmol Vis Sci. 2003;44:3598-605 pubmed
    ..Future studies will investigate the potential role of Bax and Bak in mediating pathologic photoreceptor death. ..
  49. Chen C. Recoverin and rhodopsin kinase. Adv Exp Med Biol. 2002;514:101-7 pubmed
    ..This interaction imparts a negative feedback loop at the receptor level and may play an important role in light adaptation and in recovery. ..
  50. Weiergräber O, Senin I, Philippov P, Granzin J, Koch K. Impact of N-terminal myristoylation on the Ca2+-dependent conformational transition in recoverin. J Biol Chem. 2003;278:22972-9 pubmed
    ..e. the T conformation) during the stepwise transition toward the fully Ca2+-occupied state. On the basis of these observations, a refined model for the role of the myristoyl group as an intrinsic allosteric modulator is proposed. ..
  51. Valentine K, Mesleh M, Opella S, Ikura M, Ames J. Structure, topology, and dynamics of myristoylated recoverin bound to phospholipid bilayers. Biochemistry. 2003;42:6333-40 pubmed
    ..These results demonstrate that membrane binding by recoverin is achieved primarily by insertion of the myristoyl group inside the bilayer with apparently little rearrangement of the protein structure. ..
  52. Permyakov S, Cherskaya A, Wasserman L, Khokhlova T, Senin I, Zargarov A, et al. Recoverin is a zinc-binding protein. J Proteome Res. 2003;2:51-7 pubmed
    ..Possible implications of these findings to the functioning of recoverin are discussed. ..
  53. Yamada G, Ohguro H, Aketa K, Itoh T, Shijubo N, Takahashi H, et al. Invasive thymoma with paraneoplastic retinopathy. Hum Pathol. 2003;34:717-9 pubmed
    ..Immunofluorescence staining showed that thymoma cells also expressed recoverin. These observations strongly suggested that similar pathogenesis of CAR was involved in the presented case. ..