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PR01635

Identifier
LVDCCALPHA1C  [View Relations]  [View Alignment]  
Accession
PR01635
No. of Motifs
13
Creation Date
20-DEC-2001
Title
Voltage-dependent L-type calcium channel alpha-1C 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. TAKIMOTO, K., LI, D., NERBONNE, J.M. AND LEVITAN, E.S.
Distribution, splicing and glucocorticoid-induced expression of cardiac
alpha 1C and alpha 1D voltage-gated Ca2+ channel mRNAs.
J.MOL.CELL CARDIOL. 29(11) 3035-42 (1997).
 
6. SOLDATOV, N.M., ZUHLKE, R.D., BOURON, A. AND REUTER, H.
Molecular structures involved in L-type calcium channel inactivation. Role
of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in
the kinetics and Ca2+ dependence of inactivation.
J.BIOL.CHEM. 272 3560-3566 (1997).
 
7. WEI, X., NEELY, A., OLCESE, R., LANG, W., STEFANI, E. AND BIRNBAUMER, L.
Increase in Ca2+ channel expression by deletions at the amino terminus of
the cardiac alpha 1C subunit.
RECEPTORS CHANNELS 4(4) 205-215 (1996).

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].
 
Alpha1-C subunits can be found in a number of excitable tissues, as well as
the heart and lungs [5]. The variability in the C-terminal region of the
alpha-1C subunit generated by alternative splicing influences the kinetics,
calcium- and voltage-dependence of L-type channels [6]. The N-terminus
is also a site of significant structural diversity [7].
 
LVDCCALPHA1C is a 13-element fingerprint that provides a signature for the
voltage-dependent L-type calcium channel alpha-1C subunit. The fingerprint
was derived from an initial alignment of 5 sequences: the motifs were drawn 
from conserved regions spanning the full alignment length, focusing on those
sections that characterise the alpha-1C subunit but distinguish it from
other members of the alpha-1 subunit family - motifs 1-3 reside at the 
N-terminus; motifs 4-6 lie in the cytoplasmic region between TM domain 6 of 
repeat II and TM domain 1 of repeat III; motif 7 encodes part of repeat IV;
and motifs 8-13 span the cytoplasmic region between TM domain 6 of repeat IV
and TM domain 1 of repeat V. A single iteration on SPTR40_18f was required
to reach convergence, no further sequences being identified beyond the 
starting set.
Summary Information
5 codes involving 13 elements
0 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
135555555555555
120000000000000
110000000000000
100000000000000
90000000000000
80000000000000
70000000000000
60000000000000
50000000000000
40000000000000
30000000000000
20000000000000
12345678910111213
True Positives
CICC_RABIT    CICC_RAT      Q01815        Q13936        
Q9Z305
Sequence Titles
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).
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).
Q13936 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1C SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 1, CARDIAC MUSCLE) - HOMO SAPIENS (HUMAN).
Q9Z305 L-TYPE CALCIUM CHANNEL ALPHA 1 SUBUNIT - Cavia porcellus (Guinea pig).
Scan History
SPTR40_18f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GSNYGSPRPAHANMNA CICC_RAT 47 47 -
GSNYGSPRPAHANMNA Q01815 17 17 -
GSNYGSPRPAHANMNA Q13936 17 17 -
GSNYGSPRPAHANMNA CICC_RABIT 47 47 -
GSNYGSPRPAHANINA Q9Z305 46 46 -

Motif 2 width=16
Element Seqn Id St Int Rpt
NAAAGLAPEHIPTPGA CICC_RAT 63 0 -
NAAAGLAPEHIPTPGA Q01815 33 0 -
NAAAGLAPEHIPTPGA Q13936 33 0 -
NAAAGLAPEHIPTPGA CICC_RABIT 63 0 -
NAAAGLAPEHIPTPGA Q9Z305 62 0 -

Motif 3 width=17
Element Seqn Id St Int Rpt
LMGSAGNATISTVSSTQ CICC_RAT 94 15 -
LMGSAGNATISTVSSTQ Q01815 64 15 -
LMGSAGNATISTVSSTQ Q13936 64 15 -
LMGSAGNATISTVSSTQ CICC_RABIT 94 15 -
LMGSAGNTTISTVSSTQ Q9Z305 93 15 -

Motif 4 width=20
Element Seqn Id St Int Rpt
QEVMEKPAVEESKEEKIELK CICC_RAT 818 707 -
QEVMEKPAVEESKEEKIELK Q01815 788 707 -
QELVEKPAVGESKEEKIELK Q13936 788 707 -
QEVVGKPALEEAKEEKIELK CICC_RABIT 818 707 -
QEVVEKPAVEETKEEKIELK Q9Z305 817 707 -

Motif 5 width=20
Element Seqn Id St Int Rpt
SITADGESPPTTKINMDDLQ CICC_RAT 838 0 -
SITADGESPPTTKINMDDLQ Q01815 808 0 -
SITADGESPPATKINMDDLQ Q13936 808 0 -
SITADGESPPTTKINMDDLQ CICC_RABIT 838 0 -
SITADGESPPTTKINMDDLQ Q9Z305 837 0 -

Motif 6 width=17
Element Seqn Id St Int Rpt
PSENEDKSPHSNPDTAG CICC_RAT 858 0 -
PSENEDKSPHSNPDTAG Q01815 828 0 -
PNENEDKSPYPNPETTG Q13936 828 0 -
PNESEDKSPYPNPETTG CICC_RABIT 858 0 -
PNENEDKSPYPNPDAAG Q9Z305 857 0 -

Motif 7 width=15
Element Seqn Id St Int Rpt
APESEPSNSTEGETP CICC_RAT 1461 586 -
APESEPSNSTEGETP Q01815 1432 587 -
APESEPSNSTEGETP Q13936 1480 635 -
APESEPHNSTEGETP CICC_RABIT 1462 587 -
APESDPSNSTEGETP Q9Z305 1461 587 -

Motif 8 width=13
Element Seqn Id St Int Rpt
LDKAMKEAVSAAS CICC_RAT 1708 232 -
LDKAMKEAVSAAS Q01815 1679 232 -
LDKAMKEAVSAAS Q13936 1727 232 -
LDKAMKEAVSAAS CICC_RABIT 1709 232 -
LDKAMKEAVSAAS Q9Z305 1708 232 -

Motif 9 width=19
Element Seqn Id St Int Rpt
TESPSHEKLVDSTFTPSSY CICC_RAT 1769 48 -
TESPSHEKLVDSTFTPSSY Q01815 1740 48 -
TESPSHEKLVDSTFTPSSY Q13936 1788 48 -
TESPSHEKLVDSTFTPSSY CICC_RABIT 1770 48 -
TESPSHEKLVDSTFTPSSY Q9Z305 1769 48 -

Motif 10 width=17
Element Seqn Id St Int Rpt
SSTGSNANINNANNTAL CICC_RAT 1788 0 -
SSTGSNANINNANNTAL Q01815 1759 0 -
SSTGSNANINNANNTAL Q13936 1807 0 -
SSTGSNANINNANNTAL CICC_RABIT 1789 0 -
SSTGSNANISNANNTAL Q9Z305 1788 0 -

Motif 11 width=21
Element Seqn Id St Int Rpt
EYCSEPSLLSTDILSYQDDEN CICC_RAT 1875 70 -
EYCSEPSLLSTDMFSYQEDEH Q01815 1845 69 -
EACSEPSLLSTEMLSYQDDEN Q13936 1929 105 -
ECCSEPSLLSTEMLSYQDDEN CICC_RABIT 1876 70 -
EYCSEPSLLSTEMLSYKDDEN Q9Z305 1875 70 -

Motif 12 width=11
Element Seqn Id St Int Rpt
GGDISQKTALP CICC_RAT 1940 44 -
GGDISQKTALP Q01815 1910 44 -
GGDISQKTVLP Q13936 1994 44 -
GGDISQKTVLP CICC_RABIT 1941 44 -
GGDISQKTVLP Q9Z305 1940 44 -

Motif 13 width=15
Element Seqn Id St Int Rpt
PIPTLRLEGAESSEK CICC_RAT 1997 46 -
PIPTLRLEGAESSEK Q01815 1967 46 -
PVPTLRLEGVESSEK Q13936 2051 46 -
PIPTLRLEGADSSEK CICC_RABIT 1998 46 -
PIPTLRLEGAESCEK Q9Z305 1997 46 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
GSNYGSPRPAHANMNA CICC_RAT 47 47 -
GSNYGSPRPAHANMNA Q01815 17 17 -
GSNYGSPRPAHANMNA Q13936 17 17 -
GSNYGSPRPAHANMNA CICC_RABIT 47 47 -
GSNYGSPRPAHANINA Q9Z305 46 46 -

Motif 2 width=16
Element Seqn Id St Int Rpt
NAAAGLAPEHIPTPGA CICC_RAT 63 0 -
NAAAGLAPEHIPTPGA Q01815 33 0 -
NAAAGLAPEHIPTPGA Q13936 33 0 -
NAAAGLAPEHIPTPGA CICC_RABIT 63 0 -
NAAAGLAPEHIPTPGA Q9Z305 62 0 -

Motif 3 width=17
Element Seqn Id St Int Rpt
LMGSAGNATISTVSSTQ CICC_RAT 94 15 -
LMGSAGNATISTVSSTQ Q01815 64 15 -
LMGSAGNATISTVSSTQ Q13936 64 15 -
LMGSAGNATISTVSSTQ CICC_RABIT 94 15 -
LMGSAGNTTISTVSSTQ Q9Z305 93 15 -

Motif 4 width=20
Element Seqn Id St Int Rpt
QEVMEKPAVEESKEEKIELK CICC_RAT 818 707 -
QEVMEKPAVEESKEEKIELK Q01815 788 707 -
QELVEKPAVGESKEEKIELK Q13936 788 707 -
QEVVGKPALEEAKEEKIELK CICC_RABIT 818 707 -
QEVVEKPAVEETKEEKIELK Q9Z305 817 707 -

Motif 5 width=20
Element Seqn Id St Int Rpt
SITADGESPPTTKINMDDLQ CICC_RAT 838 0 -
SITADGESPPTTKINMDDLQ Q01815 808 0 -
SITADGESPPATKINMDDLQ Q13936 808 0 -
SITADGESPPTTKINMDDLQ CICC_RABIT 838 0 -
SITADGESPPTTKINMDDLQ Q9Z305 837 0 -

Motif 6 width=17
Element Seqn Id St Int Rpt
PSENEDKSPHSNPDTAG CICC_RAT 858 0 -
PSENEDKSPHSNPDTAG Q01815 828 0 -
PNENEDKSPYPNPETTG Q13936 828 0 -
PNESEDKSPYPNPETTG CICC_RABIT 858 0 -
PNENEDKSPYPNPDAAG Q9Z305 857 0 -

Motif 7 width=15
Element Seqn Id St Int Rpt
APESEPSNSTEGETP CICC_RAT 1461 586 -
APESEPSNSTEGETP Q01815 1432 587 -
APESEPSNSTEGETP Q13936 1480 635 -
APESEPHNSTEGETP CICC_RABIT 1462 587 -
APESDPSNSTEGETP Q9Z305 1461 587 -

Motif 8 width=13
Element Seqn Id St Int Rpt
LDKAMKEAVSAAS CICC_RAT 1708 232 -
LDKAMKEAVSAAS Q01815 1679 232 -
LDKAMKEAVSAAS Q13936 1727 232 -
LDKAMKEAVSAAS CICC_RABIT 1709 232 -
LDKAMKEAVSAAS Q9Z305 1708 232 -

Motif 9 width=19
Element Seqn Id St Int Rpt
TESPSHEKLVDSTFTPSSY CICC_RAT 1769 48 -
TESPSHEKLVDSTFTPSSY Q01815 1740 48 -
TESPSHEKLVDSTFTPSSY Q13936 1788 48 -
TESPSHEKLVDSTFTPSSY CICC_RABIT 1770 48 -
TESPSHEKLVDSTFTPSSY Q9Z305 1769 48 -

Motif 10 width=17
Element Seqn Id St Int Rpt
SSTGSNANINNANNTAL CICC_RAT 1788 0 -
SSTGSNANINNANNTAL Q01815 1759 0 -
SSTGSNANINNANNTAL Q13936 1807 0 -
SSTGSNANINNANNTAL CICC_RABIT 1789 0 -
SSTGSNANISNANNTAL Q9Z305 1788 0 -

Motif 11 width=21
Element Seqn Id St Int Rpt
EYCSEPSLLSTDILSYQDDEN CICC_RAT 1875 70 -
EYCSEPSLLSTDMFSYQEDEH Q01815 1845 69 -
EACSEPSLLSTEMLSYQDDEN Q13936 1929 105 -
ECCSEPSLLSTEMLSYQDDEN CICC_RABIT 1876 70 -
EYCSEPSLLSTEMLSYKDDEN Q9Z305 1875 70 -

Motif 12 width=11
Element Seqn Id St Int Rpt
GGDISQKTALP CICC_RAT 1940 44 -
GGDISQKTALP Q01815 1910 44 -
GGDISQKTVLP Q13936 1994 44 -
GGDISQKTVLP CICC_RABIT 1941 44 -
GGDISQKTVLP Q9Z305 1940 44 -

Motif 13 width=15
Element Seqn Id St Int Rpt
PIPTLRLEGAESSEK CICC_RAT 1997 46 -
PIPTLRLEGAESSEK Q01815 1967 46 -
PVPTLRLEGVESSEK Q13936 2051 46 -
PIPTLRLEGADSSEK CICC_RABIT 1998 46 -
PIPTLRLEGAESCEK Q9Z305 1997 46 -