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PR01632

Identifier
PQVDCCALPHA1  [View Relations]  [View Alignment]  
Accession
PR01632
No. of Motifs
5
Creation Date
11-DEC-2001
Title
P/Q-type voltage-dependent calcium channel alpha-1 subunit signature
Database References
PRINTS; PR00167 CACHANNEL
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. DIRIONG, S., LORY, P., WILLIAMS, M.E., ELLIS, S.B., HARPOLD, M.M. AND
TAVIAUX, S.
Chromosomal localization of the human genes for alpha 1A, alpha 1B, and
alpha 1E voltage-dependent Ca2+ channel subunits.
GENOMICS 30 605-609 (1995).

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]. P- and Q-type channels are 
formed from alpha-1A subunits and function in transmitter release [5].
P-type channels are prevalent in cerebellar Purkinje cells, but are also 
expressed in many central and peripheral neurons, such as the spinal cord 
and visual cortex. By contrast, Q-type channels are found in cerebellar 
granule neurones and the hippocampus. Different mutations in the alpha-1A
subunit produce 3 human diseases: (1) episodic ataxia type-2; (2) familial
hemiplegic migraine; and (3) spinocerebellar ataxia type-6. All 3 diseases
result in cerebellar atrophy, but they differ in the extent and rate of 
progression of neuronal degeneration [3].
 
PQVDCCALPHA1 is a 5-element fingerprint that provides a signature for the
P/Q-type voltage-dependent calcium channel alpha-1 subunits. The fingerprint
was derived from an initial alignment of 4 sequences: the motifs were drawn
from conserved regions spanning the central portion of the alignment: motifs
1-4 lie in the cytoplasmic region between repeats I and II; and motif 5
encodes part of the extracellular region between TM domains 5 and 6 of
repeat IV. 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  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
555555
400000
300000
200000
12345
True Positives
CB12_RABIT    CCP1_RAT      O00555        P97445        
Q9NS88
Sequence Titles
CB12_RABIT  VOLTAGE-DEPENDENT P/Q-TYPE CALCIUM CHANNEL ALPHA-1A SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 4) (BRAIN CALCIUM CHANNEL I) (BI) - ORYCTOLAGUS CUNICULUS (RABBIT). 
CCP1_RAT VOLTAGE-DEPENDENT P/Q-TYPE CALCIUM CHANNEL ALPHA-1A SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE, ISOFORM 4) (BRAIN CALCIUM CHANNEL I) (BI) (RAT BRAIN CLASS A) (RBA-I) - RATTUS NORVEGICUS (RAT).
O00555 VOLTAGE-DEPENDENT P/Q-TYPE CALCIUM CHANNEL ALPHA-1A SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 4) (BRAIN CALCIUM CHANNEL I) (BI) - HOMO SAPIENS (HUMAN).
P97445 VOLTAGE-DEPENDENT P/Q-TYPE CALCIUM CHANNEL ALPHA-1A SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 4) (BRAIN CALCIUM CHANNEL I) (BI) - MUS MUSCULUS (MOUSE).
Q9NS88 ALPHA1A-VOLTAGE-DEPENDENT CALCIUM CHANNEL - Homo sapiens (Human).
Scan History
SPTR40_18f 2  200  NSINGLE    
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
DARRAWPGSPERAPGREGPYG P97445 811 811 -
DARRAWPSSPERAPGREGPYG CCP1_RAT 859 859 -
DARRPWAGSQEAELSREGPYG O00555 879 879 -
DARRPWAGSQEAELSREGPYG CB12_RABIT 881 881 -

Motif 2 width=19
Element Seqn Id St Int Rpt
DADTERAKAGDAPRRHTHR P97445 851 19 -
DADPERAKAGDAPRRHTHR CCP1_RAT 899 19 -
EGEAERGKAGDPHRRHVHR O00555 918 18 -
EGEAERGKAGDPHRRHAHR CB12_RABIT 920 18 -

Motif 3 width=15
Element Seqn Id St Int Rpt
RERRHRRRKENQGSG P97445 932 62 -
RERRHRRRKESQGSG CCP1_RAT 980 62 -
KERRHRRRKENQGSG O00555 1023 86 -
RERRHRRRKDTQGSG CB12_RABIT 1033 94 -

Motif 4 width=22
Element Seqn Id St Int Rpt
PDPLPKKEEEKKEEEEADPGED P97445 1095 148 -
PDPLPKKEEEKKEEEEADPGED CCP1_RAT 1143 148 -
PDPLPKKEEEKKEEEEDDRGED O00555 1192 154 -
PDPLPKKEDEKKEEVDEGPGED CB12_RABIT 1201 153 -

Motif 5 width=15
Element Seqn Id St Int Rpt
GIDGEDEDSDEDEFQ P97445 1621 504 -
GIDGEDEDSDEDEFQ CCP1_RAT 1669 504 -
GIDVEDEDSDEDEFQ O00555 1718 504 -
GIDMEDEDSDEDEFQ CB12_RABIT 1727 504 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
DARRAWPGSPERAPGREGPYG P97445 811 811 -
DARRAWPSSPERAPGREGPYG CCP1_RAT 859 859 -
DARRPWAGSQEAELSREGPYG O00555 879 879 -
DARRPWAGSQEAELSREGPYG CB12_RABIT 881 881 -
DARRPWAGSQEAELSREDPYG Q9NS88 878 878 -

Motif 2 width=19
Element Seqn Id St Int Rpt
DADTERAKAGDAPRRHTHR P97445 851 19 -
DADPERAKAGDAPRRHTHR CCP1_RAT 899 19 -
EGEAERGKAGDPHRRHVHR O00555 918 18 -
EGEAERGKAGDPHRRHAHR CB12_RABIT 920 18 -
EGEAERGKAGDPHRRHVHR Q9NS88 917 18 -

Motif 3 width=15
Element Seqn Id St Int Rpt
RERRHRRRKENQGSG P97445 932 62 -
RERRHRRRKESQGSG CCP1_RAT 980 62 -
KERRHRRRKENQGSG O00555 1023 86 -
RERRHRRRKDTQGSG CB12_RABIT 1033 94 -
KERRHRRRKENQGSG Q9NS88 1022 86 -

Motif 4 width=22
Element Seqn Id St Int Rpt
PDPLPKKEEEKKEEEEADPGED P97445 1095 148 -
PDPLPKKEEEKKEEEEADPGED CCP1_RAT 1143 148 -
PDPLPKKEEEKKEEEEDDRGED O00555 1192 154 -
PDPLPKKEDEKKEEVDEGPGED CB12_RABIT 1201 153 -
PDPLPKKEEEKKEEEEDDRGED Q9NS88 1191 154 -

Motif 5 width=15
Element Seqn Id St Int Rpt
GIDGEDEDSDEDEFQ P97445 1621 504 -
GIDGEDEDSDEDEFQ CCP1_RAT 1669 504 -
GIDVEDEDSDEDEFQ O00555 1718 504 -
GIDMEDEDSDEDEFQ CB12_RABIT 1727 504 -
GIDVEDEDSDEDEFQ Q9NS88 1717 504 -