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PR01664

Identifier
NACHANNEL1  [View Relations]  [View Alignment]  
Accession
PR01664
No. of Motifs
4
Creation Date
13-MAR-2002
Title
Voltage-gated Na+ channel alpha 1 subunit signature
Database References
PRINTS; PR00170 NACHANNEL
Literature References
1. GEORGE, A.L., KNITTLE, T.J. AND TAMKUN, M.M.
Molecular cloning of an atypical voltage-gated sodium channel expressed in
human heart and uterus - Evidence for a distinct gene family.
PROC.NATL.ACAD.SCI.U.S.A. 89(11) 4893-4897 (1992).
 
2. NODA, M., IKEDA, T., KAYANO, T., SUZUKI, H., TAKESHIMA, H., 
KURASAKI, M., TAKAHASHI, H. AND NUMA, S.
Existence of distinct sodium channel messenger RNAs in rat brain.
NATURE 320 188-192 (1986).
 
3. NODA, M., SHIMIZU, S., TANABE, T., TAKAI, T., KAYANO, T., IKEDA, T., 
TAKAHASHI, H., NAKAYAMA, H., KANAOKA, Y., MINAMINO, M., KANGAWA, K., 
MATSUO, H., RAFTERY, M.A., HIROSE, T., INAYAMA, S., HAYASHIDA, H, 
MIYATA, T. AND NUMA, S.
Primary structure of Electrophorus electricus sodium channel deduced from 
cDNA sequence.
NATURE 312 121-127 (1984).
 
4. ROGART, R.B., CRIBBS, L.L., MUGLIA, L.K., KEPHART, D.D. AND KAISER, M.W.
Molecular cloning of a putative tetrodotoxin resistant rat heart Na+
channel isoform.
PROC.NATL.ACAD.SCI.U.S.A. 86(20) 8170-8174 (1989).
 
5. SATO, C. AND MATSUMOTO, G.
Proposed tertiary structure of the sodium channel.
BIOCHEM.BIOPHYS.RES.COMMUN. 186 1158-1167 (1992).
 
6. BRAMMER, W.J.
VLG Na (Voltage-gated sodium channels).
IN THE ION CHANNEL FACTSBOOK VOLUME IV, ACADEMIC PRESS, 1999, PP.768-838. 
 
7. ABOU-KHALIL,B., GE, Q., DESAI, R., RYTHER, R., BAZYK, A., BAILEY, R.,
HAINES, J.L., SUTCLIFFE, J.S. AND GEORGE, A.L.
Partial and generalized epilepsy with febrile seizures plus and a novel
SCN1A mutation.
NEUROLOGY 26 57(12) 2265-2272 (2001).

Documentation
Voltage-dependent sodium channels are transmembrane (TM) proteins
responsible for the depolarising phase of the action potential in most
electrically excitable cells [1]. They may exist in 3 states [3]: the
resting state, where the channel is closed; the activated state, where the
channel is open; and the inactivated state, where the channel is closed
and refractory to opening. Several different structurally and functionally
distinct isoforms are found in mammals, coded for by a multigene family
[4], these being responsible for the different types of sodium ion currents
found in excitable tissues.
                  
The structure of sodium channels is based on 4 internal repeats of a 6-helix
bundle [2] (in which 5 of the membrane-spanning segments are hydrophobic and
the other is positively charged), forming a 24-helical bundle. The charged
segments are believed to be localised within clusters formed by their 5 
hydrophobic neighbours: it is postulated that the charged domain may be the
voltage sensor region, possibly moving outward on depolarisation, causing a
conformational change. This model, proposed by Noda et al. [2], contrasts
with that of Sato and Matsumoto [5], in which the TM segments are juxtaposed
octagonally. The basic structural motif (the 6-helix bundle) is also found 
in potassium and calcium channel alpha subunits.
 
The SCN1A gene encodes the NaB1 channel and is particularly expressed in
the brain, but is also found in a variety of other tissues, ranging from the
retina to the olfactory bulb [6]. Epilepsy, a disorder of neuronal
hyperexcitability, has been associated with altered kinetics of SCN1A, as
well as delayed inactivation of SCN2A [7].
 
NACHANNEL1 is a 4-element fingerprint that provides a signature for the
voltage-gated Na+ channel alpha 1 subunit. The fingerprint was derived from
an initial alignment of 3 sequences: the motifs were drawn from conserved
regions spanning the N-terminal third of the alignment, focusing on those
sections that characterise the alpha 1 subunits but distinguish them from
the rest of the voltage-gated Na+ channel superfamily - motifs 1 and 2
reside in the loop between TM domains 5 and 6 in the first repeat; and
motifs 3 and 4 lie in the C-terminus of the fourth repeat. A single
iteration on SPTR40_18f was required to reach convergence, no further
sequences being identified beyond the starting set.
Summary Information
3 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
CIN1_HUMAN    CIN1_RAT      Q9C008        
Sequence Titles
CIN1_HUMAN  Sodium channel protein, brain I alpha subunit - Homo sapiens (Human). 
CIN1_RAT Sodium channel protein, brain I alpha subunit - Rattus norvegicus (Rat).
Q9C008 VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT SCN1A - Homo sapiens (Human).
Scan History
SPTR40_18f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
TNASLEEHSIEKNIT CIN1_HUMAN 283 283 -
TNASLEEHSIEKNIT Q9C008 283 283 -
TNASLEEHSIEKNVT CIN1_RAT 283 283 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KSYIQDSRYHYFL CIN1_HUMAN 315 17 -
KSYIQDSRYHYFL Q9C008 315 17 -
KSYIQDSRYHYFL CIN1_RAT 315 17 -

Motif 3 width=19
Element Seqn Id St Int Rpt
EKTDLTMSTAACPPSYDRV CIN1_HUMAN 1971 1643 -
EKTDLTMSTAACPPSYDRV Q9C008 1961 1633 -
EKTDLTMSTAACPPSYDRV CIN1_RAT 1971 1643 -

Motif 4 width=18
Element Seqn Id St Int Rpt
PIVEKHEQEGKDEKAKGK CIN1_HUMAN 1992 2 -
PIVEKHEQEGKDEKAKGK Q9C008 1982 2 -
PIVEKHEQEGKDEKAKGK CIN1_RAT 1992 2 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
TNASLEEHSIEKNIT CIN1_HUMAN 283 283 -
TNASLEEHSIEKNIT Q9C008 283 283 -
TNASLEEHSIEKNVT CIN1_RAT 283 283 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KSYIQDSRYHYFL CIN1_HUMAN 315 17 -
KSYIQDSRYHYFL Q9C008 315 17 -
KSYIQDSRYHYFL CIN1_RAT 315 17 -

Motif 3 width=19
Element Seqn Id St Int Rpt
EKTDLTMSTAACPPSYDRV CIN1_HUMAN 1971 1643 -
EKTDLTMSTAACPPSYDRV Q9C008 1961 1633 -
EKTDLTMSTAACPPSYDRV CIN1_RAT 1971 1643 -

Motif 4 width=18
Element Seqn Id St Int Rpt
PIVEKHEQEGKDEKAKGK CIN1_HUMAN 1992 2 -
PIVEKHEQEGKDEKAKGK Q9C008 1982 2 -
PIVEKHEQEGKDEKAKGK CIN1_RAT 1992 2 -