SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01667

Identifier
NACHANNEL8  [View Relations]  [View Alignment]  
Accession
PR01667
No. of Motifs
3
Creation Date
27-MAR-2002
Title
Voltage-gated Na+ channel alpha 8 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. VEGA-SAENZ DE MIERA, E.C., RUDY, B., SUGIMORI, M. AND LLINAS, R.
Molecular characterization of the sodium channel subunits expressed in
mammalian cerebellar purkinje cells.
PROC.NATL.ACAD.SCI.U.S.A. 94(13) 7059-7064 (1997).
 
7. SMITH, M.R., SMITH, R.D., PLUMMER, N.W., MEISLER, M.H. AND GOLDIN, A.L.
Functional analysis of the mouse Scn8a sodium channel.
J.NEUROSCI. 18(16) 6093-6102 (1998).

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 gene SCN8A encodes the voltage-gated Na+ channel alpha 8 subunit and is
strongly expressed in Purkinje cells. Sodium currents are known to generate
the rising phase and the prolonged plateau phase of cerebellar purkinje cell
action potentials. Experiments in mice with mutated SCN8A subunits suggest
its involvement in the persistent sodium current responsible for the
prolonged plateau phase [6]. The SCN8A gene is abundantly expressed
throughout the CNS and in the spinal cord. Mutations in mouse SCN8A result
in a number of neurological disorders, including paralysis, ataxia and
dystonia [7].
 
NACHANNEL8 is a 3-element fingerprint that provides a signature for the
voltage-gated Na+ channel alpha 8 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 8 subunits but distinguish them from
other members of the voltage-gated Na+ channel superfamily. Two iterations
on SPTR40_18f were required to reach convergence, at which point a true set
comprising 7 sequences was identified. Two partial matches were also found,
both of which are closely related sodium channel proteins.
Summary Information
   7 codes involving  3 elements
2 codes involving 2 elements
Composite Feature Index
3777
2112
123
True Positives
O88420        O88421        O95788        Q9DF53        
Q9NYX2 Q9UQD0 Q9WTU3
True Positive Partials
Codes involving 2 elements
Q60858 Q63541
Sequence Titles
O88420      VOLTAGE-GATED SODIUM CHANNEL RPN4 - Rattus norvegicus (Rat). 
O88421 VOLTAGE-GATED SODIUM CHANNEL VARIANT RPN4A - Rattus norvegicus (Rat).
O95788 VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT - Homo sapiens (Human).
Q9DF53 SODIUM CHANNEL PROTEIN SCN8A - Brachydanio rerio (Zebrafish) (Zebra danio).
Q9NYX2 VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT - Homo sapiens (Human).
Q9UQD0 SODIUM CHANNEL - Homo sapiens (Human).
Q9WTU3 NEURONAL VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT - Mus musculus (Mouse).

Q60858 SODIUM CHANNEL, VOLTAGE-GATED, TYPE VIII, ALPHA POLYPEPTIDE (SCN8A) - Mus musculus (Mouse).
Q63541 SODIUM CHANNEL PROTEIN 6 - Rattus norvegicus (Rat).
Scan History
SPTR40_18f 2  150  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
TVSEDAIEEEGEEGG O95788 457 457 -
TVSEDAIEEEGEDGV Q9WTU3 457 457 -
TVSEDVVEDDGDGEG Q9DF53 458 458 -

Motif 2 width=15
Element Seqn Id St Int Rpt
KKKGPGSLLVSMDQL O95788 674 202 -
KKKGPGSLLVSMEQL Q9WTU3 672 200 -
KKKLSGSLMVSVEQL Q9DF53 642 169 -

Motif 3 width=18
Element Seqn Id St Int Rpt
EADEVKPLDELYEKKANC O95788 1027 338 -
EADEVKPLDELYEKKANC Q9WTU3 1025 338 -
VTDEAKPLDDMYDRKLNC Q9DF53 996 339 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
TVSEDAIEEEGEEGG O95788 457 457 -
TVSEDAIEEEGEEGG Q9UQD0 457 457 -
TVSEDAIEEEGEEGG Q9NYX2 457 457 -
TVSEDAIEEEGEDGV Q9WTU3 457 457 -
TVSEDAIEEEGEDGV O88420 457 457 -
TVSEDAIEEEGEDGV O88421 457 457 -
TVSEDVVEDDGDGEG Q9DF53 458 458 -

Motif 2 width=15
Element Seqn Id St Int Rpt
KKKGPGSLLVSMDQL O95788 674 202 -
KKKGPGSLLVSMDQL Q9UQD0 674 202 -
KKKGPGSLLVSMDQL Q9NYX2 674 202 -
KKKGPGSLLVSMEQL Q9WTU3 672 200 -
KKKGPGSLLVSMDQL O88420 672 200 -
KKKGPGSLLVSMDQL O88421 682 210 -
KKKLSGSLMVSVEQL Q9DF53 642 169 -

Motif 3 width=18
Element Seqn Id St Int Rpt
EADEVKPLDELYEKKANC O95788 1027 338 -
EADEVKPLDELYEKKANC Q9UQD0 1027 338 -
EADEVKPLDELYEKKANC Q9NYX2 1027 338 -
EADEVKPLDELYEKKANC Q9WTU3 1025 338 -
EADEVKPLDELYEKKANC O88420 1025 338 -
EADEVKPLDELYEKKANC O88421 1035 338 -
VTDEAKPLDDMYDRKLNC Q9DF53 996 339 -