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PR00170

Identifier
NACHANNEL  [View Relations]  [View Alignment]  
Accession
PR00170
No. of Motifs
2
Creation Date
06-MAY-1993  (UPDATE 22-MAY-2000)
Title
Voltage-gated Na+ channel alpha subunit signature
Database References
PRINTS; PR01664 NACHANNEL1; PR01665 NACHANNEL4; PR01666 NACHANNEL5
PRINTS; PR01667 NACHANNEL8
INTERPRO; IPR001696
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).

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 channels alpha
subunits.
 
NACHANNEL is a 2-element fingerprint that provides a signature for voltage-
gated Na+ channel alpha subunits. The fingerprint was derived from an
initial alignment of 34 sequences: motif 1 lies on the sixth TM domain, of
the fourth internal repeat; and motif 2 encodes a portion of the putative 
cytoplasmic C-terminus. Two iterations on SPTR37_10f were required to reach
convergence, at which point a true set comprising 49 sequences was
identified.
Summary Information
49 codes involving  2 elements
Composite Feature Index
24949
12
True Positives
CIN1_LOLBL    CIN1_RAT      CIN2_RAT      CIN3_RAT      
CIN4_HUMAN CIN4_RAT CIN5_HUMAN CIN5_RAT
CIN6_HUMAN CINA_DROME CINA_ELEEL O01306
O01307 O02037 O44930 O46669
O62604 O70611 O88420 O88421
O88457 O95788 P70276 P90670
P97706 Q14472 Q15478 Q15858
Q17314 Q24528 Q24529 Q24530
Q24531 Q24532 Q25150 Q25377
Q25439 Q25440 Q28371 Q28644
Q60858 Q62205 Q62243 Q62467
Q62968 Q63541 Q63554 Q94615
Q9YGN7
Sequence Titles
CIN1_LOLBL  SODIUM CHANNEL PROTEIN I, BRAIN - LOLIGO BLEEKERI (BLEEKER'S SQUID). 
CIN1_RAT Sodium channel protein, brain I alpha subunit - Rattus norvegicus (Rat).
CIN2_RAT SODIUM CHANNEL PROTEIN, BRAIN II ALPHA SUBUNIT - RATTUS NORVEGICUS (RAT).