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PR01629

Identifier
TVDCCALPHA1  [View Relations]  [View Alignment]  
Accession
PR01629
No. of Motifs
5
Creation Date
11-DEC-2001
Title
T-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. CRIBBS, L., LEE, J.H., YANG, J., SATIN, J., ZHANG, Y., DAUD, A., 
BARCLAY, J., WILLIAMSON, M.P., FOX, M., REES, M. AND PEREZ-REYES, E.
Cloning and characterization of alpha1H from human heart, a member of the
T-type Ca2+ channel gene family.
CIRC.RES. 83 103-109 (1998).
 
6. HUGUENARD, J.R.
Low-threshold calcium currents in central nervous system neurons.
ANNU.REV.PHYSIOL. 58 329-348 (1996).
 
7. ENYEART, J.J., MLINAR, B. AND ENYEART, J.A.
T-type Ca2+ channels are required for adrenocorticotropin-stimulated
cortisol production by bovine adrenal zona fasciculata cells.
MOL.ENDOCRINOL. 7 1031-1040 (1993).
 
8. AKAIKE, N., KOSTYUK, P.G. AND OSIPCHUK, Y.V.
Dihydropyridine-sensitive low-threshold calcium channels in isolated rat
hypothalamic neurones.
J.PHYSIOL. 412 181-195 (1989).

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]. T-type calcium channels are 
composed of alpha-1G and alpha-1H subunits [5]. They exhibit unique voltage-
dependent kinetics, small single channel conductance, rapid inactivation,
slow deactivation and a relatively high permeability to calcium [6]. They
are primarily responsible for rebound burst firing in central neurons and
are implicated in normal brain functions, such as slow wave sleep, and in
diseased states, such as epilepsy [6]. They also play an important role in
hormone secretion [7] and smooth muscle excitability [8].
 
TVDCCALPHA1 is a 5-element fingerprint that provides a signature for the
T-type voltage-dependent calcium channel alpha-1 subunit. The fingerprint
was derived from an initial alignment of 6 sequences: the motifs were drawn
from conserved regions spanning the full alignment length: motif 1 lies in
the cytoplasmic N-terminus; motif 2 resides in the extracellular region
between TM domains 1 and 2 of repeat I; motif 3 spans the cytoplasmic region
between TM domain 6 of repeat I and TM domain 1 of repeat II; motif 4 
spans part of TM domain 1 of repeat II and the following extracellular
region; and motif 5 lies in the cytoplasmic region between TM domain 6 of
repeat III and domain I in repeat IV. Two iterations on SPTR40_18f were
required to reach convergence, at which point a true set comprising 12
sequences was identified. A single partial match was also found, Q9W433,
a family member from Drosophila that fails to make significant matches with 
motifs 1 and 5.
Summary Information
  12 codes involving  5 elements
0 codes involving 4 elements
1 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51212121212
400000
301110
200000
12345
True Positives
CCAG_HUMAN    CCAH_HUMAN    CCAI_RAT      O54898        
Q9EQ59 Q9EQ60 Q9JKU5 Q9NZC8
Q9P0X4 Q9UNE6 Q9WUB8 Q9WUT2
True Positive Partials
Codes involving 3 elements
Q9W433
Sequence Titles
CCAG_HUMAN  Voltage-dependent T-type calcium channel alpha-1G subunit (NBR13) (Cav3.1c) - Homo sapiens (Human). 
CCAH_HUMAN Voltage-dependent T-type calcium channel alpha-1H subunit - Homo sapiens (Human).
CCAI_RAT Voltage-dependent T-type calcium channel alpha-1I subunit (CAVT.3) - Rattus norvegicus (Rat).
O54898 LOW VOLTAGE-ACTIVATED, T-TYPE CALCIUM CHANNEL ALPHA SUBUNIT - RATTUS NORVEGICUS (RAT).
Q9EQ59 CALCIUM CHANNEL ALPHA-1-I SUBUNIT - Rattus norvegicus (Rat).
Q9EQ60 CALCIUM CHANNEL ALPHA-1-H SUBUNIT - Rattus norvegicus (Rat).
Q9JKU5 LOW-VOLTAGE-ACTIVATED CALCIUM CHANNEL ALPHA13.2 SUBUNIT - Mus musculus (Mouse).
Q9NZC8 T-TYPE CALCIUM CHANNEL ALPHA1 SUBUNIT ALPHA1I-A ISOFORM - Homo sapiens (Human).
Q9P0X4 T CALCIUM CHANNEL ALPHA1I SUBUNIT, DELTA36B SPLICE VARIANT - Homo sapiens (Human).
Q9UNE6 T-TYPE CALCIUM CHANNEL ALPHA1I SUBUNIT - Homo sapiens (Human).
Q9WUB8 T-TYPE CALCIUM CHANNEL ISOFORM - Rattus norvegicus (Rat).
Q9WUT2 VOLTAGE-GATED CALCIUM CHANNEL, ALPHA-1-G SUBUNIT - Mus musculus (Mouse).

Q9W433 CG4222 PROTEIN - Drosophila melanogaster (Fruit fly).
Scan History
SPTR40_18f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
FFCLRQTTSPRNWCIKM Q9UNE6 59 59 -
FFCLRQTTSPRNWCIKM CCAI_RAT 57 57 -
FFCLRQTTSPRNWCIKM Q9EQ59 57 57 -
FFYLSQDSRPRSWCLRT CCAG_HUMAN 61 61 -
FFYLSQDSRPRSWCLRT O54898 61 61 -
FFCLGQTTRPRSWCLRL CCAH_HUMAN 80 80 -

Motif 2 width=17
Element Seqn Id St Int Rpt
PCDDMDCLSDRCKILQV Q9UNE6 101 25 -
PCDDMECLSDRCKILQV CCAI_RAT 99 25 -
PCDDMECLSDRCKILQV Q9EQ59 99 25 -
PCEDIACDSQRCRILQA CCAG_HUMAN 103 25 -
PCEDIACDSQRCRILQA O54898 103 25 -
PCEDVECGSERCNILEA CCAH_HUMAN 122 25 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EPGDCYEEIFQYVCH Q9UNE6 430 312 -
EPGDCYEEIFQYVCH CCAI_RAT 428 312 -
EPGDCYEEIFQYVCH Q9EQ59 428 312 -
EPGSCYEELLKYLVY CCAG_HUMAN 428 308 -
EPGSCYEELLKYLVY O54898 428 308 -
EPGSCYEELLKYVGH CCAH_HUMAN 452 313 -

Motif 4 width=14
Element Seqn Id St Int Rpt
GIEHHEQPEELTNI Q9UNE6 658 213 -
GIEHHEQPEELTNI CCAI_RAT 616 173 -
GIEHHEQPEELTNI Q9EQ59 616 173 -
GIEYHEQPEELTNA CCAG_HUMAN 761 318 -
GIEYHEQPEELTNA O54898 762 319 -
GVEYHEQPEELTNA CCAH_HUMAN 811 344 -

Motif 5 width=16
Element Seqn Id St Int Rpt
EAEEARRREEKRLRRL Q9UNE6 1442 770 -
EAEEARRREEKRLRRL CCAI_RAT 1401 771 -
EAEEARRREEKRLRRL Q9EQ59 1400 770 -
EEEEARRREEKRLRRL CCAG_HUMAN 1548 773 -
EEEEARRREEKRLRRL O54898 1527 751 -
EAEEARRREEKRLRRL CCAH_HUMAN 1566 741 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
FFCLRQTTSPRNWCIKM Q9NZC8 59 59 -
FFCLRQTTSPRNWCIKM Q9UNE6 59 59 -
FFCLRQTTSPRNWCIKM Q9P0X4 59 59 -
FFCLRQTTSPRNWCIKM CCAI_RAT 57 57 -
FFCLRQTTSPRNWCIKM Q9EQ59 57 57 -
FFYLSQDSRPRSWCLRT CCAG_HUMAN 61 61 -
FFYLSQDSRPRSWCLRT O54898 61 61 -
FFYLSQDSRPRSWCLRT Q9WUB8 61 61 -
FFYLSQDSRPRSWCLRT Q9WUT2 61 61 -
FFCLGQTTRPRSWCLRL CCAH_HUMAN 80 80 -
FFCLGQTTRPRSWCLRL Q9EQ60 80 80 -
FFCLGQTTRPRSWCLRL Q9JKU5 80 80 -

Motif 2 width=17
Element Seqn Id St Int Rpt
PCDDMDCLSDRCKILQV Q9NZC8 101 25 -
PCDDMDCLSDRCKILQV Q9UNE6 101 25 -
PCDDMDCLSDRCKILQV Q9P0X4 101 25 -
PCDDMECLSDRCKILQV CCAI_RAT 99 25 -
PCDDMECLSDRCKILQV Q9EQ59 99 25 -
PCEDIACDSQRCRILQA CCAG_HUMAN 103 25 -
PCEDIACDSQRCRILQA O54898 103 25 -
PCEDIACDSQRCRILQA Q9WUB8 103 25 -
PCEDIACDSQRCRILQA Q9WUT2 103 25 -
PCEDVECGSERCNILEA CCAH_HUMAN 122 25 -
PCEDVECRSERCSILEA Q9EQ60 122 25 -
PCEDVECRSERCSILEA Q9JKU5 122 25 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EPGDCYEEIFQYVCH Q9NZC8 430 312 -
EPGDCYEEIFQYVCH Q9UNE6 430 312 -
EPGDCYEEIFQYVCH Q9P0X4 430 312 -
EPGDCYEEIFQYVCH CCAI_RAT 428 312 -
EPGDCYEEIFQYVCH Q9EQ59 428 312 -
EPGSCYEELLKYLVY CCAG_HUMAN 428 308 -
EPGSCYEELLKYLVY O54898 428 308 -
EPGSCYEELLKYLVY Q9WUB8 428 308 -
EPGSCYEELLKYLVY Q9WUT2 428 308 -
EPGSCYEELLKYVGH CCAH_HUMAN 452 313 -
EPGSCYEELLKYVGH Q9EQ60 452 313 -
EPGSCYEELLKYVGH Q9JKU5 452 313 -

Motif 4 width=14
Element Seqn Id St Int Rpt
GIEHHEQPEELTNI Q9NZC8 623 178 -
GIEHHEQPEELTNI Q9UNE6 658 213 -
GIEHHEQPEELTNI Q9P0X4 658 213 -
GIEHHEQPEELTNI CCAI_RAT 616 173 -
GIEHHEQPEELTNI Q9EQ59 616 173 -
GIEYHEQPEELTNA CCAG_HUMAN 761 318 -
GIEYHEQPEELTNA O54898 762 319 -
GIEYHEQPEELTNA Q9WUB8 762 319 -
GIEYHEQPEELTNA Q9WUT2 761 318 -
GVEYHEQPEELTNA CCAH_HUMAN 811 344 -
GVEYHEQPEELTNA Q9EQ60 808 341 -
GVEYHEQPDELTNA Q9JKU5 808 341 -

Motif 5 width=16
Element Seqn Id St Int Rpt
EAEEARRREEKRLRRL Q9NZC8 1407 770 -
EAEEARRREEKRLRRL Q9UNE6 1442 770 -
EAEEARRREEKRLRRL Q9P0X4 1442 770 -
EAEEARRREEKRLRRL CCAI_RAT 1401 771 -
EAEEARRREEKRLRRL Q9EQ59 1400 770 -
EEEEARRREEKRLRRL CCAG_HUMAN 1548 773 -
EEEEARRREEKRLRRL O54898 1527 751 -
EEEEARRREEKRLRRL Q9WUB8 1550 774 -
EEEEARRREEKRLKRL Q9WUT2 1549 774 -
EAEEARRREEKRLRRL CCAH_HUMAN 1566 741 -
EAEEARRREEKRLRRL Q9EQ60 1577 755 -
EAEEARRREEKRLRRL Q9JKU5 1577 755 -