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PR01666

Identifier
NACHANNEL5  [View Relations]  [View Alignment]  
Accession
PR01666
No. of Motifs
7
Creation Date
13-MAR-2002
Title
Voltage-gated Na+ channel alpha 5 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. BREMMER, D.J.
VLG Na (Voltage-gated sodium channels).
IN THE ION CHANNEL FACTSBOOK IV, ACADEMIC PRESS, 1999, PP.768-838.
 
7. WANG, Q., SHEN, J., SPLAWSKI, I., ATKINSON, D., LI, Z., ROBINSON, J.L.,
MOSS, A.J., TOWBIN, J.A. AND KEATING, M.T.
SCN5A mutations associated with an inherited cardiac arrhythmia, long QT
syndrome.
CELL 10 80(5) 805-11 (1995).
 
8. ANTZELEVITCH, C.
Ion channels and ventricular arrhythmias: cellular and ionic mechanisms
underlying the Brugada syndrome.
CURR.OPIN.CARDIOL. 14(3) 274-279 (1999).
 
9. SCHOTT, J.J., ALSHINAWI, C., KYNDT, F., PROBST, W., HOORNTJE, T.M.
HULSBEEK, M., WILDE, A.A., ESCANDE, D., MANNENS, M.M. AND LE MAREC, H.
Cardiac conduction defects associate with mutations in SCN5A.
NAT.GENET. 23 (1) 20-21 (1999).

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 SCN5A gene encodes the NaH1 channel and is expressed in cardiac muscle,
foetal skeletal muscle and denervated adult skeletal muscle [6]. Mutations
in the SCN5A gene affect the function of NaH1 channels in the heart and are
one of the three causes of Long QT syndrome, an inherited cardiac arrhythmia
that can cause abrupt loss of consciousness, seizures and sudden death [7]; 
it is also associated  with Brugada syndrome [8] and conduction system
disease [9].
 
NACHANNEL5 is a 7-element fingerprint that provides a signature for the
voltage-gated Na+ channel alpha 5 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-5 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 of the first repeat; motifs 
3-5 lie in the loop between TM domain 6 of the first repeat and TM domain 1
of the second repeat; and motifs 6 and 7 encompass the loop between TM 6 of
the second repeat and TM 1 of the third. 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  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
73333333
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
CIN5_HUMAN    CIN5_RAT      Q9JJV9        
Sequence Titles
CIN5_HUMAN  Sodium channel protein, cardiac muscle alpha-subunit (HH1) - Homo sapiens (Human). 
CIN5_RAT Sodium channel protein, cardiac muscle alpha-subunit - Rattus norvegicus (Rat).
Q9JJV9 VOLTAGE-GATED SODIUM CHANNEL - Mus musculus (Mouse).
Scan History
SPTR40_18f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
DGLVWNSLDVYLNDP CIN5_RAT 298 298 -
DGIVWNSLDVYLNDP Q9JJV9 297 297 -
DGLVWESLDLYLSDP CIN5_HUMAN 297 297 -

Motif 2 width=14
Element Seqn Id St Int Rpt
NYLLKNGTTDVLLC CIN5_RAT 314 1 -
NYLLKNGTTDVLLC Q9JJV9 313 1 -
NYLLKNGTSDVLLC CIN5_HUMAN 313 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EHEALTIRGVDTVSR CIN5_RAT 445 117 -
EHEALTIRGVDTVSR Q9JJV9 444 117 -
EHEALTIRGVDTVSR CIN5_HUMAN 444 117 -

Motif 4 width=21
Element Seqn Id St Int Rpt
ALNQLSLTHGLSRTSMRPRSS CIN5_RAT 506 46 -
ALNQLSLTHGLSRTSMRPRSS Q9JJV9 505 46 -
AMNHLSLTRGLSRTSMKPRSS CIN5_HUMAN 505 46 -

Motif 5 width=18
Element Seqn Id St Int Rpt
PPDTTTPSEEPGGPQMLT CIN5_RAT 628 101 -
PPDTTTPSEEPGGPQMLT Q9JJV9 627 101 -
PPDTTTPSEEPGGPQMLT CIN5_HUMAN 627 101 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KRTTWDFCCGILRRRPKKP CIN5_RAT 977 331 -
KRTTWDFCCGLLRRRPKKP Q9JJV9 976 331 -
KRTTWDFCCGLLRHRPQKP CIN5_HUMAN 974 329 -

Motif 7 width=17
Element Seqn Id St Int Rpt
RKETRFEEDKRPGQGTP CIN5_RAT 1026 30 -
RKETRFEEDKRPGQGTP Q9JJV9 1025 30 -
RKETQFEEGEQPGQGTP CIN5_HUMAN 1023 30 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
DGLVWNSLDVYLNDP CIN5_RAT 298 298 -
DGIVWNSLDVYLNDP Q9JJV9 297 297 -
DGLVWESLDLYLSDP CIN5_HUMAN 297 297 -

Motif 2 width=14
Element Seqn Id St Int Rpt
NYLLKNGTTDVLLC CIN5_RAT 314 1 -
NYLLKNGTTDVLLC Q9JJV9 313 1 -
NYLLKNGTSDVLLC CIN5_HUMAN 313 1 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EHEALTIRGVDTVSR CIN5_RAT 445 117 -
EHEALTIRGVDTVSR Q9JJV9 444 117 -
EHEALTIRGVDTVSR CIN5_HUMAN 444 117 -

Motif 4 width=21
Element Seqn Id St Int Rpt
ALNQLSLTHGLSRTSMRPRSS CIN5_RAT 506 46 -
ALNQLSLTHGLSRTSMRPRSS Q9JJV9 505 46 -
AMNHLSLTRGLSRTSMKPRSS CIN5_HUMAN 505 46 -

Motif 5 width=18
Element Seqn Id St Int Rpt
PPDTTTPSEEPGGPQMLT CIN5_RAT 628 101 -
PPDTTTPSEEPGGPQMLT Q9JJV9 627 101 -
PPDTTTPSEEPGGPQMLT CIN5_HUMAN 627 101 -

Motif 6 width=19
Element Seqn Id St Int Rpt
KRTTWDFCCGILRRRPKKP CIN5_RAT 977 331 -
KRTTWDFCCGLLRRRPKKP Q9JJV9 976 331 -
KRTTWDFCCGLLRHRPQKP CIN5_HUMAN 974 329 -

Motif 7 width=17
Element Seqn Id St Int Rpt
RKETRFEEDKRPGQGTP CIN5_RAT 1026 30 -
RKETRFEEDKRPGQGTP Q9JJV9 1025 30 -
RKETQFEEGEQPGQGTP CIN5_HUMAN 1023 30 -