WORKLIST ENTRIES (1):
LVDCCALPHA1D View alignment Voltage-dependent L-type calcium channel alpha-1D subunit signature
Type of fingerprint: COMPOUND with 5 elements
Links:
PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1
PRINTS; PR01631 NVDCCALPHA1; PR01632 PQVDCCALPHA1; PR01633 RVDCCALPHA1
PRINTS; PR01634 LVDCCALPHA1S; PR01635 LVDCCALPHA1C
Creation date 20-DEC-2001
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).
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 FINGERPRINT INDEX
5| 4 4 4 4 4
4| 0 0 0 0 0
3| 0 0 0 0 0
2| 0 0 0 1 1
--+--------------------------
| 1 2 3 4 5
True positives..
CCAD_HUMAN CCAD_RAT CCAD_MESAU CCAD_CHICK
Subfamily: Codes involving 2 elements
Subfamily True positives..
Q9UDC3
PROTEIN TITLES
CCAD_HUMAN Voltage-dependent L-type calcium channel alpha-1D subunit (C
CCAD_RAT Voltage-dependent L-type calcium channel alpha-1D subunit (C
CCAD_MESAU Voltage-dependent L-type calcium channel alpha-1D subunit (C
CCAD_CHICK Voltage-dependent L-type calcium channel alpha-1D subunit (C
Q9UDC3 NEURONAL-TYPE VOLTAGE-GATED CA2+ CHANNEL CLASS D ALPHA 1 SUB
SCAN HISTORY
SPTR40_18f 1 100 NSINGLE
INITIAL MOTIF SETS
LVDCCALPHA1D1 Length of motif = 20 Motif number = 1
Voltage-dependent L-type calcium channel alpha-1D subunit motif I - 1
PCODE ST INT
EANYARGTRLPLSGEGPTSQ CCAD_HUMAN 23 23
EANYARGTRLPISGEGPTSQ CCAD_RAT 23 23
EANYASSTRIPLPGDGPTTQ CCAD_CHICK 15 15
EANYARGTRPPISGEGPTSQ CCAD_MESAU 22 22
LVDCCALPHA1D2 Length of motif = 12 Motif number = 2
Voltage-dependent L-type calcium channel alpha-1D subunit motif II - 1
PCODE ST INT
QTMSTSAPPPVG CCAD_HUMAN 67 24
QTMSTSAPPPVG CCAD_RAT 67 24
QNMNTTTAQPVG CCAD_CHICK 62 27
QTMSTSAPPPVG CCAD_MESAU 66 24
LVDCCALPHA1D3 Length of motif = 14 Motif number = 3
Voltage-dependent L-type calcium channel alpha-1D subunit motif III - 1
PCODE ST INT
ETEGGNHSSGKSGG CCAD_HUMAN 220 141
ETEGGNHSSGKSGG CCAD_RAT 220 141
ETEGGSHSGGKPGG CCAD_CHICK 215 141
ETEGGNHSSGKSGG CCAD_MESAU 219 141
LVDCCALPHA1D4 Length of motif = 18 Motif number = 4
Voltage-dependent L-type calcium channel alpha-1D subunit motif IV - 1
PCODE ST INT
ENKKNNKPEVNQIANSDN CCAD_HUMAN 784 550
ENKKNNKPEVNQIANSDN CCAD_RAT 843 609
ENKKSEKSEGDQKKPKDS CCAD_CHICK 805 576
ENKKNNKPEVNQIANSDN CCAD_MESAU 783 550
LVDCCALPHA1D5 Length of motif = 16 Motif number = 5
Voltage-dependent L-type calcium channel alpha-1D subunit motif V - 1
PCODE ST INT
KDPYPPCDVPVGEEEE CCAD_HUMAN 815 13
KDPYPPCDVPVGEEEE CCAD_RAT 874 13
KDPYPPCDVPVGEDEE CCAD_CHICK 837 14
KDPYPPCDVPVGEEEE CCAD_MESAU 814 13
FINAL MOTIF SETS
LVDCCALPHA1D1 Length of motif = 20 Motif number = 1
Voltage-dependent L-type calcium channel alpha-1D subunit motif I - 1
PCODE ST INT
EANYARGTRLPLSGEGPTSQ CCAD_HUMAN 23 23
EANYARGTRLPISGEGPTSQ CCAD_RAT 23 23
EANYARGTRPPISGEGPTSQ CCAD_MESAU 22 22
EANYASSTRIPLPGDGPTTQ CCAD_CHICK 15 15
LVDCCALPHA1D2 Length of motif = 12 Motif number = 2
Voltage-dependent L-type calcium channel alpha-1D subunit motif II - 1
PCODE ST INT
QTMSTSAPPPVG CCAD_HUMAN 67 24
QTMSTSAPPPVG CCAD_RAT 67 24
QTMSTSAPPPVG CCAD_MESAU 66 24
QNMNTTTAQPVG CCAD_CHICK 62 27
LVDCCALPHA1D3 Length of motif = 14 Motif number = 3
Voltage-dependent L-type calcium channel alpha-1D subunit motif III - 1
PCODE ST INT
ETEGGNHSSGKSGG CCAD_HUMAN 220 141
ETEGGNHSSGKSGG CCAD_RAT 220 141
ETEGGNHSSGKSGG CCAD_MESAU 219 141
ETEGGSHSGGKPGG CCAD_CHICK 215 141
LVDCCALPHA1D4 Length of motif = 18 Motif number = 4
Voltage-dependent L-type calcium channel alpha-1D subunit motif IV - 1
PCODE ST INT
ENKKNNKPEVNQIANSDN CCAD_HUMAN 784 550
ENKKNNKPEVNQIANSDN CCAD_RAT 843 609
ENKKNNKPEVNQIANSDN CCAD_MESAU 783 550
ENKKSEKSEGDQKKPKDS CCAD_CHICK 805 576
LVDCCALPHA1D5 Length of motif = 16 Motif number = 5
Voltage-dependent L-type calcium channel alpha-1D subunit motif V - 1
PCODE ST INT
KDPYPPCDVPVGEEEE CCAD_HUMAN 815 13
KDPYPPCDVPVGEEEE CCAD_RAT 874 13
KDPYPPCDVPVGEEEE CCAD_MESAU 814 13
KDPYPPCDVPVGEDEE CCAD_CHICK 837 14
User query: Display/Full Code "LVDCCALPHA1D"