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PR01602

Identifier
VDCCGAMMA2  [View Relations]  [View Alignment]  
Accession
PR01602
No. of Motifs
3
Creation Date
07-SEP-2001
Title
Voltage-dependent calcium channel gamma-2 subunit signature
Database References
PRINTS; PR01792 VDCCGAMMA
MIM; 602911
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. LETTS, V., FELIX, R., BIDDLECOME, G., ARIKKATH, J., MAHAFFEY, C.,
VALENZULA, A., BARTLETT, F, MORI, Y., CAMPBELL, K. AND FRANKEL, W. 
The mouse stargazer gene encodes a neuronal Ca(2+)-channel gamma subunit. 
NAT.GENET. 19 340-347 (1998). 
 
7. CHEN, L., CHETKOVICH, D., PETRALLA, R., SWEENEY, N., KAWASKI, Y.,
WENTHOLD, R., BREDT, D. AND NICOLI, R.
Stargazin regulates synaptic targeting of AMPA receptors by two distinct 
mechanisms.
NATURE 408 936-943 (2000). 

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-2 subunit (also known as stargazin) was isolated by identifying 
the locus of the genetic disruption in the epileptic mouse mutant line
known as stargazer [6]. VDCCG-2 subunits are brain specific and enriched in
synaptic plasma membranes. In vitro studies using recombinant P/Q-type 
calcium channels show that VDCCG-2 subunit expression increases steady-state
channel inactivation, leading to the suggestion that, in stargazer mutants, 
inappropriate calcium entry may contribute to the seizure phenotype [6].
 
VDCCG-2 subunits are also implicated in cellular trafficking. They interact 
with ionotropic glutamate AMPA receptor subunits, a process that has been
shown to be essential in delivering functional AMPA receptors to the surface
membranes of cerebellar granule cells [7]. In addition, VDCCG-2 subunits
are capable of associating with PDZ proteins, such as PSD-95, through their 
C-terminal PDZ binding domains. This interaction is required to target AMPA
receptors to cerebellar synapses [7].
 
VDCCGAMMA2 is a 3-element fingerprint that provides a signature for the
voltage-dependent calcium channel gamma-2 subunit proteins. The fingerprint
was derived from an initial alignment of 3 sequences: the motifs were drawn
from conserved regions in the C-terminal portion of the alignment, focusing
on those sections that characterise the VDCCG-2 subunits but distinguish 
them from other family members - motifs 1, 2 and 3 all lie within the C-
terminal cytoplasmic tail region. A single iteration on SPTR39.22_17.3f was
required to reach convergence, no further sequences being identified beyond 
the starting set.
Summary Information
3 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3333
2000
123
True Positives
CCG2_HUMAN    CCG2_MOUSE    Q99PR9        
Sequence Titles
CCG2_HUMAN  Voltage-dependent calcium channel gamma-2 subunit (Neuronal voltage- gated calcium channel gamma-2 subunit) - Homo sapiens (Human). 
CCG2_MOUSE Voltage-dependent calcium channel gamma-2 subunit (Neuronal voltage- gated calcium channel gamma-2 subunit) (Stargazin) - Mus musculus (Mouse).
Q99PR9 IPR328 PROTEIN - Rattus norvegicus (Rat).
Scan History
SPTR39.22_17.3f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
LQASAITRIP CCG2_MOUSE 218 218 -
LQASAITRIP Q99PR9 218 218 -
LQASAITRIP CCG2_HUMAN 218 218 -

Motif 2 width=10
Element Seqn Id St Int Rpt
KAATTPTATY CCG2_MOUSE 279 51 -
KAATTPIATY Q99PR9 279 51 -
KAATTPTATY CCG2_HUMAN 279 51 -

Motif 3 width=13
Element Seqn Id St Int Rpt
HNCIQKDSKDSLH CCG2_MOUSE 300 11 -
HNCIQKDSKDSLH Q99PR9 300 11 -
HNCIQKENKDSLH CCG2_HUMAN 300 11 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
LQASAITRIP CCG2_MOUSE 218 218 -
LQASAITRIP Q99PR9 218 218 -
LQASAITRIP CCG2_HUMAN 218 218 -

Motif 2 width=10
Element Seqn Id St Int Rpt
KAATTPTATY CCG2_MOUSE 279 51 -
KAATTPIATY Q99PR9 279 51 -
KAATTPTATY CCG2_HUMAN 279 51 -

Motif 3 width=13
Element Seqn Id St Int Rpt
HNCIQKDSKDSLH CCG2_MOUSE 300 11 -
HNCIQKDSKDSLH Q99PR9 300 11 -
HNCIQKENKDSLH CCG2_HUMAN 300 11 -