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PR01631

Identifier
NVDCCALPHA1  [View Relations]  [View Alignment]  
Accession
PR01631
No. of Motifs
7
Creation Date
11-DEC-2001
Title
N-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. LUEBKE, J.I., DUNLAP, K. AND TURNER, T.J.
Multiple calcium channel types control glutamatergic synaptic transmission
in the hippocampus.
NEURON 11 895-902 (1993).
 
6. TURNER, T.J., ADAMS, M.E. AND DUNLAP, K.
Multiple Ca2+ channel types coexist to regulate synaptosomal
neurotransmitter release.
PROC.NATL.ACAD.SCI.U.S.A. 90 9518-9522 (1993).
 
7. HIRNING, L.D., FOX, A.P., MCCLESKEY, E.W., OLIVERA, B.M., THAYER, S.A.,
MILLER, R.J. AND TSIEN, R.E.
Dominant role of N-type Ca2+ channels in evoked release of norepinephrine
from sympathetic neurons.
SCIENCE 239 57-61 (1988).

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]. N-type calcium channels are
composed from alpha-1B subunits. Experiments employing CTX have demonstrated
the physiological importance of the N-type calcium channels in the nervous
system, where they have a significant developmental role in the migration 
of immature neurons before the establishment of their synaptic circuit. In 
peripheral neurons, such as autonomic neurons, motor neurons and spinal
cord neurons, they have also been shown to be critically involved in the
release of neurotransmitters, including glutamate [5], gamma-amino-butyric
acid, acetylcholine, dopamine [6] and norepinephrine [7].
 
NVDCCALPHA1 is a 7-element fingerprint that provides a signature for the
N-type voltage-dependent calcium channel alpha-1 subunit. The fingerprint
was derived from an initial alignment of 5 sequences: the motifs were drawn
from conserved regions spanning the full alignment length: motif 1 lies in
the extracellular region between TM domains 5 and 6 of repeat I; motifs 2-6
encode the cytoplasmic region between the sixth TM domain of repeat II and
TM domain 1 of repeat III; and motif 7 resides in the cytoplasmic C-terminus.
Two iterations on SPTR40_18f were required to reach convergence, at which 
point a true set comprising 15 sequences was identified.
Summary Information
15 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
715151515151515
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
CCAB_DISOM    CIC5_HUMAN    CIC5_RAT      O55017        
O89089 Q05152 Q9PUM3 Q9PUM4
Q9PUM5 Q9PUM6 Q9PW44 Q9PW45
Q9PW46 Q9PW47 Q9TTA4
Sequence Titles
CCAB_DISOM  Probable voltage-dependent N-type calcium channel alpha-1B subunit (DOE-4) - Discopyge ommata (Electric ray). 
CIC5_HUMAN VOLTAGE-DEPENDENT N-TYPE CALCIUM CHANNEL ALPHA-1B SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 5) (BRAIN CALCIUM CHANNEL III) (BIII) - HOMO SAPIENS (HUMAN).
CIC5_RAT VOLTAGE-DEPENDENT N-TYPE CALCIUM CHANNEL ALPHA-1B SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 5) (BRAIN CALCIUM CHANNEL III) (BIII) - RATTUS NORVEGICUS (RAT).
O55017 VOLTAGE-DEPENDENT N-TYPE CALCIUM CHANNEL ALPHA-1B SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 5) (BRAIN CALCIUM CHANNEL III) (BIII) - MUS MUSCULUS (MOUSE).
O89089 PORE-FORMING CALCIUM CHANNEL ALPHA-1B SUBUNIT VARIANT A - Rattus norvegicus (Rat).
Q05152 VOLTAGE-DEPENDENT N-TYPE CALCIUM CHANNEL ALPHA-1B SUBUNIT (CALCIUM CHANNEL, L TYPE, ALPHA-1 POLYPEPTIDE ISOFORM 5) (BRAIN CALCIUM CHANNEL III) (BIII) - ORYCTOLAGUS CUNICULUS (RABBIT).
Q9PUM3 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB4 VARIANT - Gallus gallus (Chicken).
Q9PUM4 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB3 VARIANT - Gallus gallus (Chicken).
Q9PUM5 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB2 VARIANT - Gallus gallus (Chicken).
Q9PUM6 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB1 VARIANT - Gallus gallus (Chicken).
Q9PW44 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB8 VARIANT - Gallus gallus (Chicken).
Q9PW45 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB7 VARIANT - Gallus gallus (Chicken).
Q9PW46 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB6 VARIANT - Gallus gallus (Chicken).
Q9PW47 N-TYPE CALCIUM CHANNEL ALPHA-1B CDB5 VARIANT - Gallus gallus (Chicken).
Q9TTA4 N-TYPE CALCIUM CHANNEL ALPHA1B SUBUNIT - Bos taurus (Bovine).
Scan History
SPTR40_18f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
DPVGDFPCGKEAP Q05152 261 261 -
EPVGDFPCGKEAP CIC5_HUMAN 261 261 -
DPVGDFPCGREAP Q9TTA4 261 261 -
EPVGDFPCGKDPP O55017 261 261 -
EPVEEFPCGTKYP CCAB_DISOM 253 253 -

Motif 2 width=14
Element Seqn Id St Int Rpt
LRLQNLRASCEALY Q05152 776 502 -
LRLQNLRASCEALY CIC5_HUMAN 775 501 -
LRLQNLRASCEALY Q9TTA4 775 501 -
LRLQNLRASCEALY O55017 775 501 -
LRRQHILTSQEALF CCAB_DISOM 766 500 -

Motif 3 width=17
Element Seqn Id St Int Rpt
APEGADPPRRHHRHRDK Q05152 842 52 -
APEGVDPPRRHHRHRDK CIC5_HUMAN 841 52 -
AGEGADPPRRHHRHRDR Q9TTA4 841 52 -
ATESADLPRRHHRHRDR O55017 841 52 -
QPESCEAPRRSHRHRDK CCAB_DISOM 838 58 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RHHRRGSPEEAA Q05152 922 63 -
RHHRRGSPEEAA CIC5_HUMAN 917 59 -
RHHRRGSPEEAA Q9TTA4 920 62 -
RHHRRGSPEEAT O55017 909 51 -
HHHAQSSLDDAP CCAB_DISOM 912 57 -

Motif 5 width=16
Element Seqn Id St Int Rpt
PSTCLQKVEEQPEDAD Q05152 1049 115 -
PSTCLQKVEEQPEDAD CIC5_HUMAN 1044 115 -
PSTCLEKVEEQPEDAD Q9TTA4 1037 105 -
PSTCLQKVDEQPEDAD O55017 1033 112 -
PPIGLQHLPQQPEDAD CCAB_DISOM 1035 111 -

Motif 6 width=17
Element Seqn Id St Int Rpt
TTVHIPVTLTGPPGETT Q05152 1081 16 -
TIVHIPVMLTGPLGEAT CIC5_HUMAN 1076 16 -
TAVRIPVTLTGPPGETT Q9TTA4 1069 16 -
TTVHVPVTLTGPPGETP O55017 1065 16 -
ATVNIPVTVTTPAAEMT CCAB_DISOM 1069 18 -

Motif 7 width=20
Element Seqn Id St Int Rpt
HHHRCHRRRDRKQRSLEKGP Q05152 2053 955 -
HHHRCHRRRDRKQRSLEKGP CIC5_HUMAN 2052 959 -
HHHRCHRRRDRKQKSLEKGP Q9TTA4 2042 956 -
HHHRCHRRRDKKQRSLEKGP O55017 2042 960 -
HHHRCHHRREKKQRSLERAT CCAB_DISOM 2044 958 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
EPVGDFPCGKEAP CIC5_HUMAN 261 261 -
EPVGDFPCGKEAP CIC5_RAT 261 261 -
EPVGDFPCGKEAP O89089 261 261 -
DPVGDFPCGREAP Q9TTA4 261 261 -
EPVGDFPCGKDPP O55017 261 261 -
EPVEEFPCGTKYP CCAB_DISOM 253 253 -
EEVGDFPCGEEPP Q9PUM3 252 252 -
EEVGDFPCGEEPP Q9PW47 252 252 -
EEVGDFPCGEEPP Q9PW46 252 252 -
EEVGDFPCGEEPP Q9PW45 252 252 -
EEVGDFPCGEEPP Q9PW44 252 252 -
EEVGDFPCGEEPP Q9PUM6 252 252 -
DPVGDFPCGKEAP Q05152 261 261 -
EEVGDFPCGEEPP Q9PUM5 252 252 -
EEVGDFPCGEEPP Q9PUM4 252 252 -

Motif 2 width=14
Element Seqn Id St Int Rpt
IRMHNFRASCEALY Q9PUM6 791 526 -
LRLQNLRASCEALY Q05152 776 502 -
LRLQNLRASCEALY CIC5_HUMAN 775 501 -
LRLQNLRASCEALY CIC5_RAT 776 502 -
LRLQNLRASCEALY O89089 775 501 -
LRLQNLRASCEALY Q9TTA4 775 501 -
LRLQNLRASCEALY O55017 775 501 -
LRRQHILTSQEALF CCAB_DISOM 766 500 -
IRMHNFRASCEALY Q9PUM3 755 490 -
IRMHNFRASCEALY Q9PW47 780 515 -
IRMHNFRASCEALY Q9PW46 780 515 -
IRMHNFRASCEALY Q9PW45 766 501 -
IRMHNFRASCEALY Q9PW44 766 501 -
IRMHNFRASCEALY Q9PUM5 791 526 -
IRMHNFRASCEALY Q9PUM4 755 490 -

Motif 3 width=17
Element Seqn Id St Int Rpt
APEGADPPRRHHRHRDK Q05152 842 52 -
APEGVDPPRRHHRHRDK CIC5_HUMAN 841 52 -
ATEGADPPRRHHRHRDR CIC5_RAT 842 52 -
ATEGADPPRRHHRHRDR O89089 841 52 -
AGEGADPPRRHHRHRDR Q9TTA4 841 52 -
ATESADLPRRHHRHRDR O55017 841 52 -
QPESCEAPRRSHRHRDK CCAB_DISOM 838 58 -
STDGAEAPRKHHRHRDK Q9PUM3 827 58 -
STDGAEAPRKHHRHRDK Q9PW47 852 58 -
STDGAEAPRKHHRHRDK Q9PUM4 827 58 -
STDGAEAPRKHHRHRDK Q9PW46 852 58 -
STDGAEAPRKHHRHRDK Q9PW45 838 58 -
STDGAEAPRKHHRHRDK Q9PW44 838 58 -
STDGAEAPRKHHRHRDK Q9PUM6 863 58 -
STDGAEAPRKHHRHRDK Q9PUM5 863 58 -

Motif 4 width=12
Element Seqn Id St Int Rpt
RHHRRGSPEEAA Q05152 922 63 -
RHHRRGSPEEAA CIC5_HUMAN 917 59 -
RHHRRGSPEEAT CIC5_RAT 915 56 -
RHHRRGSPEEAT O89089 914 56 -
RHHRRGSPEEAA Q9TTA4 920 62 -
RHHRRGSPEEAT O55017 909 51 -
HHHAQSSLDDAP CCAB_DISOM 912 57 -
RHHRRGSVEEGV Q9PUM3 901 57 -
RHHRRGSVEEGV Q9PW47 926 57 -
RHHRRGSVEEGV Q9PW46 926 57 -
RHHRRGSVEEGV Q9PW45 912 57 -
RHHRRGSVEEGV Q9PW44 912 57 -
RHHRRGSVEEGV Q9PUM6 937 57 -
RHHRRGSVEEGV Q9PUM5 937 57 -
RHHRRGSVEEGV Q9PUM4 901 57 -

Motif 5 width=16
Element Seqn Id St Int Rpt
PSTCLQKVEEQPEDAD Q05152 1049 115 -
PSTCLQKVEEQPEDAD CIC5_HUMAN 1044 115 -
PSTCLQKVDEQPEDAD CIC5_RAT 1042 115 -
PSTCLQKVDEQPEDAD O89089 1041 115 -
PSTCLEKVEEQPEDAD Q9TTA4 1037 105 -
PSTCLQKVDEQPEDAD O55017 1033 112 -
PPIGLQHLPQQPEDAD CCAB_DISOM 1035 111 -
PSTYLQKVPEQPEDAD Q9PUM3 1030 117 -
PSTYLQKVPEQPEDAD Q9PW47 1055 117 -
PSTYLQKVPEQPEDAD Q9PW46 1055 117 -
PSTYLQKVPEQPEDAD Q9PW45 1041 117 -
PSTYLQKVPEQPEDAD Q9PW44 1041 117 -
PSTYLQKVPEQPEDAD Q9PUM6 1066 117 -
PSTYLQKVPEQPEDAD Q9PUM5 1066 117 -
PSTYLQKVPEQPEDAD Q9PUM4 1030 117 -

Motif 6 width=17
Element Seqn Id St Int Rpt
TTVHIPVTLTGPPGETT Q05152 1081 16 -
TIVHIPVMLTGPLGEAT CIC5_HUMAN 1076 16 -
TTVHVPVTLTGPPGEAT CIC5_RAT 1074 16 -
TTVHVPVTLTGPPGEAT O89089 1073 16 -
TAVRIPVTLTGPPGETT Q9TTA4 1069 16 -
TTVHVPVTLTGPPGETP O55017 1065 16 -
ATVNIPVTVTTPAAEMT CCAB_DISOM 1069 18 -
TTVNIPVTITAPPGETT Q9PUM3 1062 16 -
TTVNIPVTITAPPGETT Q9PW47 1087 16 -
TTVNIPVTITAPPGETT Q9PW46 1087 16 -
TTVNIPVTITAPPGETT Q9PW45 1073 16 -
TTVNIPVTITAPPGETT Q9PW44 1073 16 -
TTVNIPVTITAPPGETT Q9PUM6 1098 16 -
TTVNIPVTITAPPGETT Q9PUM5 1098 16 -
TTVNIPVTITAPPGETT Q9PUM4 1062 16 -

Motif 7 width=20
Element Seqn Id St Int Rpt
HHHRCHRRRDRKQRSLEKGP Q05152 2053 955 -
HHHRCHRRRDRKQRSLEKGP CIC5_HUMAN 2052 959 -
HHHRCHRRRDKKQRSLEKGP CIC5_RAT 2051 960 -
HHHRCHRRRDKKQRSLEKGP O89089 2048 958 -
HHHRCHRRRDRKQKSLEKGP Q9TTA4 2042 956 -
HHHRCHRRRDKKQRSLEKGP O55017 2042 960 -
HHHRCHHRREKKQRSLERAT CCAB_DISOM 2044 958 -
HHHRCHRRKEKKQKSLDRTT Q9PUM3 2045 966 -
HHHRCHRRKEKKQKSLDRTT Q9PW47 2070 966 -
HHHRCHRRKEKKQKSLDRTT Q9PW46 2070 966 -
HHHRCHRRKEKKQKSLDRTT Q9PW45 2056 966 -
HHHRCHRRKEKKQKSLDRTT Q9PW44 2056 966 -
HHHRCHRRKEKKQKSLDRTT Q9PUM6 2081 966 -
HHHRCHRRKEKKQKSLDRTT Q9PUM5 2081 966 -
HHHRCHRRKEKKQKSLDRTT Q9PUM4 2045 966 -