WORKLIST ENTRIES (1):

NACHANNEL1 View alignment       Voltage-gated Na+ channel alpha 1 subunit signature
 Type of fingerprint: COMPOUND with 4  elements
Links:
   PRINTS; PR00170 NACHANNEL; PR01665 NACHANNEL4; PR01666 NACHANNEL5 
   PRINTS; PR01667 NACHANNEL8

 Creation date 13-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. BRAMMER, W.J.
   VLG Na (Voltage-gated sodium channels).
   IN THE ION CHANNEL FACTSBOOK VOLUME IV, ACADEMIC PRESS, 1999, PP.768-838. 

   7. ABOU-KHALIL,B., GE, Q., DESAI, R., RYTHER, R., BAZYK, A., BAILEY, R.,
   HAINES, J.L., SUTCLIFFE, J.S. AND GEORGE, A.L.
   Partial and generalized epilepsy with febrile seizures plus and a novel
   SCN1A mutation.
   NEUROLOGY 26 57(12) 2265-2272 (2001).

   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 SCN1A gene encodes the NaB1 channel and is particularly expressed in
   the brain, but is also found in a variety of other tissues, ranging from the
   retina to the olfactory bulb [6]. Epilepsy, a disorder of neuronal
   hyperexcitability, has been associated with altered kinetics of SCN1A, as
   well as delayed inactivation of SCN2A [7].
  
   NACHANNEL1 is a 4-element fingerprint that provides a signature for the
   voltage-gated Na+ channel alpha 1 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 1 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 in the first repeat; and
   motifs 3 and 4 lie in the C-terminus of the fourth repeat. 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  4 elements
      0 codes involving  3 elements
      0 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    4|   3    3    3    3  
    3|   0    0    0    0  
    2|   0    0    0    0  
   --+---------------------
     |   1    2    3    4  

True positives..
 CIN1_HUMAN     Q9C008         CIN1_RAT       


  PROTEIN TITLES
   CIN1_HUMAN       Sodium channel protein, brain I alpha subunit - Homo sapiens
   Q9C008           VOLTAGE-GATED SODIUM CHANNEL ALPHA SUBUNIT SCN1A - Homo sapi
   CIN1_RAT         Sodium channel protein, brain I alpha subunit - Rattus norve

SCAN HISTORY SPTR40_18f 1 100 NSINGLE INITIAL MOTIF SETS NACHANNEL11 Length of motif = 15 Motif number = 1 Voltage-gated Na+ channel alpha 1 subunit motif I - 1 PCODE ST INT TNASLEEHSIEKNIT CIN1_HUMAN 283 283 TNASLEEHSIEKNVT CIN1_RAT 283 283 TNASLEEHSIEKNIT Q9C008 283 283 NACHANNEL12 Length of motif = 13 Motif number = 2 Voltage-gated Na+ channel alpha 1 subunit motif II - 1 PCODE ST INT KSYIQDSRYHYFL CIN1_HUMAN 315 17 KSYIQDSRYHYFL CIN1_RAT 315 17 KSYIQDSRYHYFL Q9C008 315 17 NACHANNEL13 Length of motif = 19 Motif number = 3 Voltage-gated Na+ channel alpha 1 subunit motif III - 1 PCODE ST INT EKTDLTMSTAACPPSYDRV CIN1_HUMAN 1971 1643 EKTDLTMSTAACPPSYDRV CIN1_RAT 1971 1643 EKTDLTMSTAACPPSYDRV Q9C008 1961 1633 NACHANNEL14 Length of motif = 18 Motif number = 4 Voltage-gated Na+ channel alpha 1 subunit motif IV - 1 PCODE ST INT PIVEKHEQEGKDEKAKGK CIN1_HUMAN 1992 2 PIVEKHEQEGKDEKAKGK CIN1_RAT 1992 2 PIVEKHEQEGKDEKAKGK Q9C008 1982 2 FINAL MOTIF SETS NACHANNEL11 Length of motif = 15 Motif number = 1 Voltage-gated Na+ channel alpha 1 subunit motif I - 1 PCODE ST INT TNASLEEHSIEKNIT CIN1_HUMAN 283 283 TNASLEEHSIEKNIT Q9C008 283 283 TNASLEEHSIEKNVT CIN1_RAT 283 283 NACHANNEL12 Length of motif = 13 Motif number = 2 Voltage-gated Na+ channel alpha 1 subunit motif II - 1 PCODE ST INT KSYIQDSRYHYFL CIN1_HUMAN 315 17 KSYIQDSRYHYFL Q9C008 315 17 KSYIQDSRYHYFL CIN1_RAT 315 17 NACHANNEL13 Length of motif = 19 Motif number = 3 Voltage-gated Na+ channel alpha 1 subunit motif III - 1 PCODE ST INT EKTDLTMSTAACPPSYDRV CIN1_HUMAN 1971 1643 EKTDLTMSTAACPPSYDRV Q9C008 1961 1633 EKTDLTMSTAACPPSYDRV CIN1_RAT 1971 1643 NACHANNEL14 Length of motif = 18 Motif number = 4 Voltage-gated Na+ channel alpha 1 subunit motif IV - 1 PCODE ST INT PIVEKHEQEGKDEKAKGK CIN1_HUMAN 1992 2 PIVEKHEQEGKDEKAKGK Q9C008 1982 2 PIVEKHEQEGKDEKAKGK CIN1_RAT 1992 2

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