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PR01634

Identifier
LVDCCALPHA1S  [View Relations]  [View Alignment]  
Accession
PR01634
No. of Motifs
3
Creation Date
20-DEC-2001
Title
Voltage-dependent L-type calcium channel alpha-1S subunit signature
Database References
PRINTS; PR00167 CACHANNEL; PR01630 LVDCCALPHA1
Literature References
1. WILLIAMS, M.E., BRUST. P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., 
MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M.
Structure and functional expression of an omega-conotoxin sensitive human
N-type calcium channel.
SCIENCE 257 389-395 (1992).
 
2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., 
BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., 
IMOTO, K., TANABE, T. AND NUMA, S.
Primary structure and functional expression from complementary DNA of a 
brain calcium channel.
NATURE 350 398-402 (1991).
 
3. ASHCROFT, F.M.
Voltage-gated Ca2+ channels.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.161-183.
 
4. KOCH, W.J., ELLINOR, P.T. AND SCHWARTZ, A.
cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta -
evidence for the existence of alternatively spliced forms.
J.BIOL.CHEM. 265(29) 17786-17791 (1990).
 
5. TANABE, T. TAKESHIMA, H., MIKAMI, A., FLOCKERZI, V., TAKAHASHI, H.,
KANGAWA, K., KOJIMA, M., MATSUO, H., HIROSE, T. AND NUMA, S. 
Primary structure of the receptor for calcium channel blockers from skeletal
muscle. 
NATURE 328 313-318 (1987).
 
6. HOFMANN, F., BIEL, M. AND FLOCKERZI, V.
Molecular basis for Ca2+ channel diversity.
ANNU.REV.NEUROSCI. 17 399-418 (1994).
 
7. CONLEY, E.C. AND BRAMMAR, W.J.
Voltage-gated calcium channels.
IN THE ION CHANNEL FACTSBOOK, VOLUME IV, ACADEMIC PRESS, 1999, PP.22-153.

Documentation
Calcium channel proteins are involved in the control of neurotransmitter
release from neurons [1], and play an important role in the regulation of a
variety of cellular functions, including membrane excitability, muscle
contraction and synaptic transmission [2]. Voltage-gated calcium channels
are classified as T, L, N, P, Q and R, and are distinguished by their
sensitivity to pharmacological blocks, single-channel conductance kinetics,
and voltage-dependence. On the basis of their voltage activation
properties, the voltage-gated calcium classes can be further divided into
two broad groups: the low (T-type) and high (L, N, P, Q and R-type)
threshold-activated channels [3].
 
Generally, the channel proteins are composed of 4 tightly-coupled subunits
(alpha-1, alpha-2, beta and gamma), the alpha-1 subunit from each creating
the pore for the import of extracellular calcium ions. The alpha-1 subunit
shares sequence characteristics with all voltage-dependent cation channels,
and exploits the same 6-helix bundle structural motif - in both sodium and
calcium channels, this motif is repeated 4 times within the sequence to give
a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM)
segments (S1, S2, S3, S5, S6) are hydrophobic and one is positively charged
(S4) - the latter is characterised by charged amino acids at very third
position, and probably represents the voltage-sensor.
 
Several genes encoding alpha-1 subunits have been identified, each forming
a distinct electrophysiological channel [4]. L-type calcium channels are
formed from alpha-1S, alpha-1C and alpha-1D subunits. They are widely 
distributed and are well characterised in the heart, smooth and skeletal
muscle, and some neurons. Their primary functions are in both excitation-
contraction and excitation-secretion coupling. In skeletal muscle, the 
L-type calcium channels act as a voltage sensor for excitation-contraction
coupling and, in cardiac muscle, they provide a pathway for calcium influx. 
Mutations affecting L-type channel subunits result in three diseases: 
(1) muscular dystrophy, which is characterised by a lack of functional 
skeletal muscle; (2) hypokalaemic periodic paralysis, which is characterised
by episodic attacks of skeletal muscle weakness; and (3) malignant
hyperthermia, which is the main cause of death due to anaesthesia [3].
 
The cDNA encoding the alpha-1S subunit from rabbit skeletal muscle was the
first calcium channel subunit sequence to be cloned [5]. The alpha-1S 
subunit is present in skeletal muscle and has also been detected in kidney
and brain [5,6]. In the skeletal muscle, it is present in two size variants,
a full-length, minor (~5%) form of ~212kDa, and a major (~95%) species of
~190kDa, derived from the longer protein by post-translational cleavage [7].
 
LVDCCALPHA1S is a 3-element fingerprint that provides a signature for the
voltage-dependent L-type calcium channel alpha-1S subunit. The fingerprint
was derived from an initial alignment of 3 sequences: the motifs were drawn 
from conserved regions spanning the N-terminal portion of the alignment,
focusing on those sections that characterise the alpha-1S subunit but
distinguish it from other members of the alpha-1 subunit family - motif 1
lies in the cytoplasmic region between TM domain 6 of repeat I and TM domain
1 of repeat II; and motifs 2 and 3 reside in the cytoplasmic region between
TM domain 6 of repeat II and TM domain 1 of repeat III. Two iterations on
SPTR40_18f were required to reach convergence, at which point a true set
comprising 5 sequences was identified.
Summary Information
5 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3555
2000
123
True Positives
CIC1_CYPCA    CIC1_RABIT    O57483        Q02789        
Q13698
Sequence Titles
CIC1_CYPCA  DIHYDROPYRIDINE-SENSITIVE L-TYPE, SKELETAL MUSCLE CALCIUM CHANNEL ALPHA-1 SUBUNIT - CYPRINUS CARPIO (COMMON CARP). 
CIC1_RABIT DIHYDROPYRIDINE-SENSITIVE L-TYPE, SKELETAL MUSCLE CALCIUM CHANNEL ALPHA-1 SUBUNIT - ORYCTOLAGUS CUNICULUS (RABBIT).
O57483 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL, ALPHA-1S SUBUNIT (FGALPHA1S) - Rana catesbeiana (Bull frog).
Q02789 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL, ALPHA-1S SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 3, SKELETAL MUSCLE) - Mus musculus (Mouse).
Q13698 DIHYDROPRYRIDINE-SENSITIVE L-TYPE, SKELETAL MUSCLE CALCIUM CHANNEL ALPHA-1 SUBUNIT - HOMO SAPIENS (HUMAN).
Scan History
SPTR40_18f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
SDTESLYEIE CIC1_RABIT 393 393 -
SDTESLYEIA Q13698 393 393 -
SESDSLYQML CIC1_CYPCA 409 409 -

Motif 2 width=17
Element Seqn Id St Int Rpt
EGIPTTAKLKVDEFESN CIC1_RABIT 712 309 -
EGIPTTAKLKIDEFESN Q13698 712 309 -
EGMPTTAKLKIDEFESN CIC1_CYPCA 728 309 -

Motif 3 width=15
Element Seqn Id St Int Rpt
VNEVKDPYPSADFPG CIC1_RABIT 729 0 -
VNEVKDPYPSADFPG Q13698 729 0 -
VNEVKDPFPPADFPG CIC1_CYPCA 745 0 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
SDTESLYEIE Q02789 393 393 -
SDTESLYEIE CIC1_RABIT 393 393 -
SDTESLYEIA Q13698 393 393 -
SETDSLYEIE O57483 392 392 -
SESDSLYQML CIC1_CYPCA 409 409 -

Motif 2 width=17
Element Seqn Id St Int Rpt
EGIPTTAKLKIDEFESN Q02789 712 309 -
EGIPTTAKLKVDEFESN CIC1_RABIT 712 309 -
EGIPTTAKLKIDEFESN Q13698 712 309 -
EGIPTTARLKIDEFESN O57483 710 308 -
EGMPTTAKLKIDEFESN CIC1_CYPCA 728 309 -

Motif 3 width=15
Element Seqn Id St Int Rpt
VNEVKDPYPSADFPG Q02789 729 0 -
VNEVKDPYPSADFPG CIC1_RABIT 729 0 -
VNEVKDPYPSADFPG Q13698 729 0 -
VNEIKDPYPSADFPG O57483 727 0 -
VNEVKDPFPPADFPG CIC1_CYPCA 745 0 -