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 . They may exist in 3 states : 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 , 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  (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. , contrasts with that of Sato and Matsumoto , 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 . 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 . 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
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