| Literature References | 1. BITO, H., DEISSEROTH, K. AND TSIEN, R.
Ca2+-dependent regulation in neuronal gene expression.
CURR.OPIN.NEUROBIOL. 7 419-429 (1997).
2. DUNLAP, K., LEUBKE, J. AND TURNER, T.
Exocytotic calcium channels in mammalian central neurons.
TRENDS NEUROSCI. 18 89-98 (1995).
3. AHLIJANIAN, M., WESTENBROEK, R. AND CATTERALL, W.
Subunit structure and localization of dihydropyridine-sensitive calcium
channels in mammalian brain, spinal cord, and retina.
NEURON 4 819-832 (1990).
4. WITCHER, D., DE WAARD, M., SAKAMOTO, J., FRANZINI-ARMSTRONG, C.,
PRAGNELL, M., KAHL, S. AND CAMPBELL, K.
Subunit identification and reconstitution of the N-type Ca2+ channel complex
purified from brain.
SCIENCE 261 486-489 (1993).
5. BURGESS, D., GEFRIDES, L., FOREMAN, P. AND NOEBELS, J.
A cluster of three novel Ca2+ channel gamma subunit genes on chromosome
19q13.4: evolution and expression profile of the gamma subunit gene family.
GENOMICS 71 339-350 (2001).
6. KLUGBAUER, N., DAI, S., SPECHT, V., LACINOVA, L., MARAIS, E., BOHN, G.
AND HOFMANN, F.
A family of gamma-like calcium channel subunits.
FEBS LETT. 470 189-197 (2000).
7. ROUSSET, M., CENS, T., RESTITUITO, S., BARRERE, C., BLACK, J., MCENERY,
M. AND CHARNET, P.
Functional roles of gamma2, gamma3 and gamma4, three new Ca2+ channel
subunits, in P/Q-type Ca2+ channel expressed in Xenopus oocytes.
J.PHYSIOL. 532 583-593 (2001).
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| Documentation | Voltage-dependent calcium channels are a diverse family of proteins that
encompass a variety of biological functions, including presynaptic
neurotransmitter release and protein signalling within the cell [1,2]. The
high voltage-activated channels (L-, N-, P-, Q- and R-type channels)
comprise the alpha-1 subunit, which creates the pore for the import of
extracellular calcium ions [2]. The activity of this pore is modulated by
four tightly-coupled subunits: an intracellular beta subunit; a
transmembrane (TM) gamma subunit; and a disulphide-linked complex of alpha-2
and delta subunits, which are proteolytically cleaved from the same gene
product [3,4].
The voltage-dependent calcium channel gamma (VDCCG) subunit family consists
of at least 8 members, which share a number of common structural features
[5]. Each member is predicted to possess four TM domains, with intracellular
N- and C- termini. The first extracellular loop contains a highly conserved
N-glycosylation site and a pair of conserved cysteine residues. The
C-terminal seven residues of VDCCG-2, -3, -4 and -8 are also conserved and
contain a consensus site for phosphorylation by cAMP and cGMP-dependent
protein kinases, and a target site for binding by PDZ domain proteins [5].
The VDCCG-4 subunit is predominantly expressed in neuronal tissue, although
there is some evidence for expression in lung and prostate [5,6]. The
modulatory properties of the subunit have been investigated using
heterologous expression systems. Coexpression of the VDCGG-4 subunit with
P/Q-type channels shifts the steady-state inactivation curve of these
channels to more hyperpolarised potentials [6,7].
VDCCGAMMA4 is a 5-element fingerprint that provides a signature for the
voltage-dependent calcium channel gamma-4 subunit proteins. The fingerprint
was derived from an initial alignment of 2 sequences: the motifs were drawn
from conserved regions spanning virtually the full alignment length,
focusing on those sections that characterise the VDCCG-4 sunbunits but
distinguish them from other family members - motif 1 lies in the first
extracellular loop; motif two spans part of TM domain 2 and extends into
the intracellular loop; and motifs 3, 4 and 5 lie in the C-terminal
cytoplasmic region. A single iteration on SPTR39.22_17.3f was required to
reach convergence, no further sequences being identified beyond the
starting set.
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