Hippocalcin Explained

Hippocalcin is a protein that in humans is encoded by the HPCA gene.^{[1] [2]}

Hippocalcin is a calcium-binding protein that belongs to the neuronal calcium sensor (NCS) family of proteins.^{[3] [4]} It is expressed in mammalian brains especially in the hippocampus. It possesses a Ca²⁺/myristoyl switch.^[5]

Processes

Hippocalcin takes part in the following processes:

• Activation of PLD1 and PLD2 expression
• Inhibition of apoptosis
• MAP kinase signalling
• Involved in long term depression in hippocampal neuron
• Required for normal spatial learning

Interactions

Hippocalcin interacts with following proteins:

• Neuronal apoptosis inhibitory protein (NAIP)
• Mixed lineage kinase 2 (MLK2) – MLK2 is myosin light chain kinase 2
• The b2 adaptin of the AP2 complex
• Calcium-dependent activator protein for secretion (CADPS)

Further reading

• Hidaka H, Okazaki K . Neurocalcin family: a novel calcium-binding protein abundant in bovine central nervous system . Neurosci. Res. . 16 . 2 . 73–7 . 1993 . 8387172 . 10.1016/0168-0102(93)90074-Z . 4210072 .
• Nagao M, Hayashi H . Mixed lineage kinase 2 and hippocalcin are localized in Lewy bodies of Parkinson's disease . J. Neurol. Sci. . 281 . 1–2 . 51–4 . 2009 . 19332348 . 10.1016/j.jns.2009.02.375 . 13177773 .
• Kobayashi M, Takamatsu K, Saitoh S, etal . Molecular cloning of hippocalcin, a novel calcium-binding protein of the recoverin family exclusively expressed in hippocampus . Biochem. Biophys. Res. Commun. . 189 . 1 . 511–7 . 1992 . 1280427 . 10.1016/0006-291X(92)91587-G .
• Nagata K, Puls A, Futter C, etal . The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3 . EMBO J. . 17 . 1 . 149–58 . 1998 . 9427749 . 1170366 . 10.1093/emboj/17.1.149 .
• Kobayashi M, Takamatsu K, Saitoh S, Noguchi T . Myristoylation of hippocalcin is linked to its calcium-dependent membrane association properties . J. Biol. Chem. . 268 . 25 . 18898–904 . 1993 . 10.1016/S0021-9258(17)46711-1 . 8360179 . free .
• Rudinskiy N, Kaneko YA, Beesen AA, etal . Diminished hippocalcin expression in Huntington's disease brain does not account for increased striatal neuron vulnerability as assessed in primary neurons . J. Neurochem. . 111 . 2 . 460–72 . 2009 . 19686238 . 10.1111/j.1471-4159.2009.06344.x . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Mercer EA, Korhonen L, Skoglösa Y, etal . NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways . EMBO J. . 19 . 14 . 3597–607 . 2000 . 10899114 . 313967 . 10.1093/emboj/19.14.3597 .
• Ivings L, Pennington SR, Jenkins R, etal . Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin . Biochem. J. . 363 . Pt 3 . 599–608 . 2002 . 11964161 . 1222513 . 10.1042/0264-6021:3630599 .
• O'Callaghan DW, Haynes LP, Burgoyne RD . High-affinity interaction of the N-terminal myristoylation motif of the neuronal calcium sensor protein hippocalcin with phosphatidylinositol 4,5-bisphosphate . Biochem. J. . 391 . Pt 2 . 231–8 . 2005 . 16053445 . 1276920 . 10.1042/BJ20051001 .
• O'Callaghan DW, Ivings L, Weiss JL, etal . Differential use of myristoyl groups on neuronal calcium sensor proteins as a determinant of spatio-temporal aspects of Ca2+ signal transduction . J. Biol. Chem. . 277 . 16 . 14227–37 . 2002 . 11836243 . 10.1074/jbc.M111750200 . free .
• Markova 0, Fitzgerald D, Stepanyuk A. Hippocalcin signaling via site-specific translocation in hippocampal neurons . Neurosci. Lett. . 442 . 2 . 152–7 . 2009 . 18634855 . 2572729 . 10.1016/j.neulet.2008.06.089 . etal.

External links

• NCS proteins

Notes and References

1. 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. . 200 . 1 . 606–11 . April 1994 . 8166736 . 10.1006/bbrc.1994.1491 .
2. Masaki T, Sakai E, Furuta Y, Kobayashi M, Takamatsu K . Genomic structure and chromosomal mapping of the human and mouse hippocalcin genes . Gene . 225 . 1–2 . 117–24 . December 1998 . 9931466 . 10.1016/S0378-1119(98)00526-5.
3. Burgoyne RD. Neuronal Calcium Sensor Proteins: Generating Diversity in Neuronal Ca2+ Signalling. Nat. Rev. Neurosci. . 8 . 3 . 182–193 . 2007 . 17311005 . 1887812 . 10.1038/nrn2093 .
4. Burgoyne RD, O'Callaghan DW, Hasdemir B, Haynes LP, Tepikin AV . Neuronal Ca2+-sensor proteins: multitalented regulators of neuronal function . Trends Neurosci. . 27 . 4 . 203–9 . 2004 . 15046879 . 10.1016/j.tins.2004.01.010 . 24156457 .
5. 10.1083/jcb.200306042 . O'Callaghan DW, Tepikin AV, Burgoyne RD . Dynamics and calcium sensitivity of the Ca2+/myristoyl switch protein hippocalcin in living cells. J. Cell Biol. . 163 . 4 . 715–721 . 2003 . 14638856 . 2173692 .