WORKLIST ENTRIES (1):
NACHANNEL8 View alignment Voltage-gated Na+ channel alpha 8 subunit signature
Type of fingerprint: COMPOUND with 3 elements
Links:
PRINTS; PR00170 NACHANNEL; PR01664 NACHANNEL1; PR01665 NACHANNEL4
PRINTS; PR01666 NACHANNEL5
Creation date 27-MAR-2002
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).
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 FINGERPRINT INDEX
3| 7 7 7
2| 1 1 2
--+----------------
| 1 2 3
True positives..
O95788 Q9UQD0 Q9NYX2 Q9WTU3
O88420 O88421 Q9DF53
Subfamily: Codes involving 2 elements
Subfamily True positives..
Q63541 Q60858
PROTEIN TITLES
O95788 VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT - Homo sapiens (H
Q9UQD0 SODIUM CHANNEL - Homo sapiens (Human).
Q9NYX2 VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT - Homo sapiens (H
Q9WTU3 NEURONAL VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT - Mus mu
O88420 VOLTAGE-GATED SODIUM CHANNEL RPN4 - Rattus norvegicus (Rat).
O88421 VOLTAGE-GATED SODIUM CHANNEL VARIANT RPN4A - Rattus norvegic
Q9DF53 SODIUM CHANNEL PROTEIN SCN8A - Brachydanio rerio (Zebrafish)
Q63541 SODIUM CHANNEL PROTEIN 6 - Rattus norvegicus (Rat).
Q60858 SODIUM CHANNEL, VOLTAGE-GATED, TYPE VIII, ALPHA POLYPEPTIDE
SCAN HISTORY
SPTR40_18f 2 150 NSINGLE
INITIAL MOTIF SETS
NACHANNEL81 Length of motif = 15 Motif number = 1
Voltage-gated Na+ channel alpha 8 subunit motif I - 1
PCODE ST INT
TVSEDAIEEEGEEGG O95788 457 457
TVSEDVVEDDGDGEG Q9DF53 458 458
TVSEDAIEEEGEDGV Q9WTU3 457 457
NACHANNEL82 Length of motif = 15 Motif number = 2
Voltage-gated Na+ channel alpha 8 subunit motif II - 1
PCODE ST INT
KKKGPGSLLVSMDQL O95788 674 202
KKKLSGSLMVSVEQL Q9DF53 642 169
KKKGPGSLLVSMEQL Q9WTU3 672 200
NACHANNEL83 Length of motif = 18 Motif number = 3
Voltage-gated Na+ channel alpha 8 subunit motif III - 1
PCODE ST INT
EADEVKPLDELYEKKANC O95788 1027 338
VTDEAKPLDDMYDRKLNC Q9DF53 996 339
EADEVKPLDELYEKKANC Q9WTU3 1025 338
FINAL MOTIF SETS
NACHANNEL81 Length of motif = 15 Motif number = 1
Voltage-gated Na+ channel alpha 8 subunit motif I - 2
PCODE ST INT
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
NACHANNEL82 Length of motif = 15 Motif number = 2
Voltage-gated Na+ channel alpha 8 subunit motif II - 2
PCODE ST INT
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
NACHANNEL83 Length of motif = 18 Motif number = 3
Voltage-gated Na+ channel alpha 8 subunit motif III - 2
PCODE ST INT
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
User query: Display/Full Code "NACHANNEL8"