| 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).
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| 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].
LVDCCALPHA1 is a 6-element fingerprint that provides a signature for the
L-type voltage-dependent calcium channel alpha-1 subunit. The fingerprint
was derived from an initial alignment of 13 sequences: the motifs were drawn
from conserved regions spanning the full alignment length: motif 1 lies in
the extracellular region between TM domains 1 and 2 of repeat I; motif 2
resides in TM domain 3 of repeat I; motif 3 encodes the cytoplasmic region
between TM domain 6 of repeat I and TM domain 1 of repeat II; motif 4 lies
in the cytoplasmic region of repeat II; motif 5 spans TM domain 3 of repeat
II; and motif 6 resides in the extracellular region between TM domains
5 and 6 in repeat II. Two iterations on SPTR40_18f were required to reach
convergence, at which point a true set comprising 18 sequences was
identified. Several partial matches were also found, all of which are
members of the L-type voltage-dependent calcium channel family that fail
to make significant matches with one or more motifs.
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| Sequence Titles | CCAD_MESAU Voltage-dependent L-type calcium channel alpha-1D subunit (Calcium channel, L type, alpha-1 polypeptide isoform 2) - Mesocricetus auratus (Golden hamster).
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).
CICB_RAT VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1D SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 2) (RAT BRAIN CLASS D) (RBD) - RATTUS NORVEGICUS (RAT).
CICC_RABIT VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1C SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 1, CARDIAC MUSCLE) (SMOOTH MUSCLE CALCIUM CHANNEL BLOCKER RECEPTOR) (CACB-RECEPTOR) - ORYCTOLAGUS CUNICULUS (RABBIT).
CICC_RAT VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL, ALPHA-1C SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 1, CARDIAC MUSCLE) (RAT BRAIN CLASS C) (RBC) - RATTUS NORVEGICUS (RAT).
O57483 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL, ALPHA-1S SUBUNIT (FGALPHA1S) - Rana catesbeiana (Bull frog).
O60840 L-TYPE CALCIUM CHANNEL ALPHA-1 SUBUNIT - HOMO SAPIENS (HUMAN).
O73700 L-TYPE VOLTAGE-GATED CALCIUM CHANNEL ALPHA1D SUBUNIT CHCACHA1D - GALLUS GALLUS (CHICKEN).
O95226 VOLTAGE-GATED L-TYPE CALCIUM CHANNEL ALPHA-1 SUBUNIT - Homo sapiens (Human).
Q01668 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1D SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 2) - HOMO SAPIENS (HUMAN).
Q01815 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL, ALPHA-1C SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 1, CARDIAC MUSCLE) (MOUSE BRAIN CLASS C) (MBC) (MELC-CC) - MUS MUSCULUS (MOUSE).
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).
Q13936 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1C SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 1, CARDIAC MUSCLE) - HOMO SAPIENS (HUMAN).
Q9JIS7 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1F SUBUNIT - Mus musculus (Mouse).
Q9UHB1 VOLTAGE-GATED L-TYPE CALCIUM CHANNEL ALPHA-1 SUBUNIT - Homo sapiens (Human).
Q9Z305 L-TYPE CALCIUM CHANNEL ALPHA 1 SUBUNIT - Cavia porcellus (Guinea pig).
O96057 ASCIDIAN CALCIUM CHANNEL ALPHA1-SUBUNIT - Halocynthia roretzi (Sea squirt).
O17050 PUTATIVE L-TYPE CALCIUM CHANNEL ALPHA 1 SUBUNIT - Caenorhabditis elegans.
O97017 L-TYPE CALCIUM CHANNEL ALPHA-1 SUBUNIT - Stylophora pistillata.
Q18698 HYPOTHETICAL PROTEIN C48A7.1 - Caenorhabditis elegans.
Q24270 CALCIUM CHANNEL ALPHA-1 SUBUNIT - DROSOPHILA MELANOGASTER (FRUIT FLY).
Q25452 VOLTAGE DEPENDENT CALCIUM CHANNEL ALPHA1 SUBUNIT - MUSCA DOMESTICA (HOUSE FLY).
Q9V3P7 CA-ALPHA1D PROTEIN - Drosophila melanogaster (Fruit fly).
O02038 VOLTAGE-GATED CALCIUM CHANNEL ALPHA-1 SUBUNIT - Cyanea capillata (Lion's mane jellyfish).
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