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PR01636

Identifier
LVDCCALPHA1D  [View Relations]  [View Alignment]  
Accession
PR01636
No. of Motifs
5
Creation Date
20-DEC-2001
Title
Voltage-dependent L-type calcium channel alpha-1D 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. KOSCHAK, A. REIMER, D. HUBER, I. GRABNER, M. GLOSSMANN, H. ENGEL, J. AND
STRIESSNIG, J.
Alpha-1D (Cav1.3) subunits can form L-type Ca2+ channels activating at
negative voltages.
J.BIOL.CHEM. 276(25) 22100-22106 (2001).
 
7. MOSER, T. AND BEUTNER, D.
Kinetics of exocytosis and endocytosis at the cochlear inner hair cell
afferent synapse of the mouse.
PROC.NATL.ACAD.SCI.U.S.A. 97 883-888 (2000).
 
8. MAGEE, J.C., AVERY, R.B., CHRISTIE, B.R. AND JOHNSTON, D.
Dihydropyridine-sensitive, voltage-gated Ca2+ channels contribute to the
resting intracellular Ca2+ concentration of hippocampal CA1 pyramidal
neurons.
J.NEUROPHYSIOL. 76 3460-3470 (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].
 
Alpha-1D subunits are expressed in the lung and heart, in particular the
aorta and atrium. Although expressed in the same areas as the alpha-1C
subunit, they are less abundant [5]. Alpha-1D subunits allow cells to slowly
inactivate voltage-gated Ca2+ influx to weak depolarisations [6]. This
property allows them to participate in important physiological functions,
such as tonic neurotransmitter release in cochlear inner hair cells [7]. 
In addition, these properties make them ideally suited to contribute to
subthreshold Ca2+ signalling, for example in hippocampal pyramidal cells [8].
 
LVDCCALPHA1D is a 5-element fingerprint that provides a signature for the
voltage-dependent L-type calcium channel alpha-1D subunit. The fingerprint
was derived from an initial alignment of 4 sequences: the motifs were drawn 
from conserved regions spanning the N-terminal portion of the alignment,
focusing on those sections that characterise the alpha-1D subunit but
distinguish it from other members of the alpha-1 subunit family - motifs 1
and 2 reside in the N-terminus; motif 3 lies in the cytoplasmic region 
between TM domains 3 and 4 of the first repeat; and motifs 4 and 5 span the
cytoplasmic region between TM domain 6 of repeat II and TM domain I of 
repeat III. A single iteration on SPTR40_18f was required to reach
convergence, no further sequences being identified beyond the starting set.
A single partial match was found, Q9UDC3, a human neuronal-type voltage-
gated Ca2+ channel class D alpha 1 subunit that matches motifs 4 and 5.
Summary Information
   4 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
544444
400000
300000
200011
12345
True Positives
CCAD_MESAU    CICB_RAT      O73700        Q01668        
True Positive Partials
Codes involving 2 elements
Q9UDC3
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). 
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).
O73700 L-TYPE VOLTAGE-GATED CALCIUM CHANNEL ALPHA1D SUBUNIT CHCACHA1D - GALLUS GALLUS (CHICKEN).
Q01668 VOLTAGE-DEPENDENT L-TYPE CALCIUM CHANNEL ALPHA-1D SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 2) - HOMO SAPIENS (HUMAN).

Q9UDC3 NEURONAL-TYPE VOLTAGE-GATED CA2+ CHANNEL CLASS D ALPHA 1 SUBUNIT, VGCC CLASS D ALPHA 1 - Homo sapiens (Human).
Scan History
SPTR40_18f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EANYARGTRLPLSGEGPTSQ Q01668 23 23 -
EANYARGTRLPISGEGPTSQ CICB_RAT 23 23 -
EANYARGTRPPISGEGPTSQ CCAD_MESAU 22 22 -
EANYASSTRIPLPGDGPTTQ O73700 15 15 -

Motif 2 width=12
Element Seqn Id St Int Rpt
QTMSTSAPPPVG Q01668 67 24 -
QTMSTSAPPPVG CICB_RAT 67 24 -
QTMSTSAPPPVG CCAD_MESAU 66 24 -
QNMNTTTAQPVG O73700 62 27 -

Motif 3 width=14
Element Seqn Id St Int Rpt
ETEGGNHSSGKSGG Q01668 220 141 -
ETEGGNHSSGKSGG CICB_RAT 220 141 -
ETEGGNHSSGKSGG CCAD_MESAU 219 141 -
ETEGGSHSGGKPGG O73700 215 141 -

Motif 4 width=18
Element Seqn Id St Int Rpt
ENKKNNKPEVNQIANSDN Q01668 784 550 -
ENKKNNKPEVNQIANSDN CICB_RAT 843 609 -
ENKKNNKPEVNQIANSDN CCAD_MESAU 783 550 -
ENKKSEKSEGDQKKPKDS O73700 805 576 -

Motif 5 width=16
Element Seqn Id St Int Rpt
KDPYPPCDVPVGEEEE Q01668 815 13 -
KDPYPPCDVPVGEEEE CICB_RAT 874 13 -
KDPYPPCDVPVGEEEE CCAD_MESAU 814 13 -
KDPYPPCDVPVGEDEE O73700 837 14 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
EANYARGTRLPLSGEGPTSQ Q01668 23 23 -
EANYARGTRLPISGEGPTSQ CICB_RAT 23 23 -
EANYARGTRPPISGEGPTSQ CCAD_MESAU 22 22 -
EANYASSTRIPLPGDGPTTQ O73700 15 15 -

Motif 2 width=12
Element Seqn Id St Int Rpt
QTMSTSAPPPVG Q01668 67 24 -
QTMSTSAPPPVG CICB_RAT 67 24 -
QTMSTSAPPPVG CCAD_MESAU 66 24 -
QNMNTTTAQPVG O73700 62 27 -

Motif 3 width=14
Element Seqn Id St Int Rpt
ETEGGNHSSGKSGG Q01668 220 141 -
ETEGGNHSSGKSGG CICB_RAT 220 141 -
ETEGGNHSSGKSGG CCAD_MESAU 219 141 -
ETEGGSHSGGKPGG O73700 215 141 -

Motif 4 width=18
Element Seqn Id St Int Rpt
ENKKNNKPEVNQIANSDN Q01668 784 550 -
ENKKNNKPEVNQIANSDN CICB_RAT 843 609 -
ENKKNNKPEVNQIANSDN CCAD_MESAU 783 550 -
ENKKSEKSEGDQKKPKDS O73700 805 576 -

Motif 5 width=16
Element Seqn Id St Int Rpt
KDPYPPCDVPVGEEEE Q01668 815 13 -
KDPYPPCDVPVGEEEE CICB_RAT 874 13 -
KDPYPPCDVPVGEEEE CCAD_MESAU 814 13 -
KDPYPPCDVPVGEDEE O73700 837 14 -