WORKLIST ENTRIES (1):

PQVDCCALPHA1 View alignment     P/Q-type voltage-dependent calcium channel alpha-1 subunit signature
 Type of fingerprint: COMPOUND with 5  elements
Links:
   PRINTS; PR00167 CACHANNEL; PR01629 TVDCCALPHA1; PR01630 LVDCCALPHA1
   PRINTS; PR01631 NVDCCALPHA1; PR01633 RVDCCALPHA1 

 Creation date 11-DEC-2001

   1. WILLIAMS, M.E., BRUST, P.F., FELDMAN, D.H., PATTHI, S., SIMERSON, S., 
   MAROUFI, A., MCCUE, A.F., VELICELBI, G., ELLIS, S.B. AND HARPOLD, M.M.
   Structure and functional expression of an omega-conotoxin sensitive human
   N-type calcium channel.
   SCIENCE 257 389-395 (1992).

   2. MORI, Y., FRIEDRICH, T., KIM, MS., MIKAMI, A., NAKAI, J., RUTH, P., 
   BOSSE, E., HOFMANN, F., FLOCKERZI, V., FURUICHI, T., MIKOSHIBA, K., 
   IMOTO, K., TANABE, T. AND NUMA, S.
   Primary structure and functional expression from complementary DNA of a 
   brain calcium channel.
   NATURE 350 398-402 (1991).

   3. ASHCROFT, F.M.
   Voltage-gated Ca2+ channels.
   IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.161-183.

   4. KOCH, W.J., ELLINOR, P.T. AND SCHWARTZ, A.
   cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta -
   evidence for the existence of alternatively spliced forms.
   J.BIOL.CHEM. 265(29) 17786-17791 (1990).

   5. DIRIONG, S., LORY, P., WILLIAMS, M.E., ELLIS, S.B., HARPOLD, M.M. AND
   TAVIAUX, S.
   Chromosomal localization of the human genes for alpha 1A, alpha 1B, and
   alpha 1E voltage-dependent Ca2+ channel subunits.
   GENOMICS 30 605-609 (1995).

   Calcium channel proteins are involved in the control of neurotransmitter
   release from neurons [1], and play an important role in the regulation of a
   variety of cellular functions, including membrane excitability, muscle
   contraction and synaptic transmission [2]. Voltage-gated calcium channels
   are classified as T, L, N, P, Q and R, and are distinguished by their
   sensitivity to pharmacological blocks, single-channel conductance kinetics,
   and voltage-dependence. On the basis of their voltage activation
   properties, the voltage-gated calcium classes can be further divided into
   two broad groups: the low (T-type) and high (L, N, P, Q and R-type)
   threshold-activated channels [3].
   
   Generally, the channel proteins are composed of 4 tightly-coupled subunits
   (alpha-1, alpha-2, beta and gamma), the alpha-1 subunit from each creating
   the pore for the import of extracellular calcium ions. The alpha-1 subunit
   shares sequence characteristics with all voltage-dependent cation channels,
   and exploits the same 6-helix bundle structural motif - in both sodium and
   calcium channels, this motif is repeated 4 times within the sequence to give
   a 24-helix bundle. Within each of these repeats, 5 of the transmembrane (TM)
   segments (S1, S2, S3, S5, S6) are hydrophobic and one is positively charged
   (S4) - the latter is characterised by charged amino acids at very third
   position, and probably represents the voltage-sensor.
  
   Several genes encoding alpha-1 subunits have been identified, each forming
   a distinct electrophysiological channel [4]. P- and Q-type channels are 
   formed from alpha-1A subunits and function in transmitter release [5].
   P-type channels are prevalent in cerebellar Purkinje cells, but are also 
   expressed in many central and peripheral neurons, such as the spinal cord 
   and visual cortex. By contrast, Q-type channels are found in cerebellar 
   granule neurones and the hippocampus. Different mutations in the alpha-1A
   subunit produce 3 human diseases: (1) episodic ataxia type-2; (2) familial
   hemiplegic migraine; and (3) spinocerebellar ataxia type-6. All 3 diseases
   result in cerebellar atrophy, but they differ in the extent and rate of 
   progression of neuronal degeneration [3].
  
   PQVDCCALPHA1 is a 5-element fingerprint that provides a signature for the
   P/Q-type voltage-dependent calcium channel alpha-1 subunits. The fingerprint
   was derived from an initial alignment of 4 sequences: the motifs were drawn
   from conserved regions spanning the central portion of the alignment: motifs
   1-4 lie in the cytoplasmic region between repeats I and II; and motif 5
   encodes part of the extracellular region between TM domains 5 and 6 of
   repeat IV. Two iterations on SPTR40_18f were required to reach convergence,
   at which point a true set comprising 5 sequences was identified.

  SUMMARY INFORMATION
      5 codes involving  5 elements
      0 codes involving  4 elements
      0 codes involving  3 elements
      0 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    5|   5    5    5    5    5  
    4|   0    0    0    0    0  
    3|   0    0    0    0    0  
    2|   0    0    0    0    0  
   --+--------------------------
     |   1    2    3    4    5  

True positives..
 CCAA_MOUSE     CCAA_RAT       CCAA_HUMAN     CCAA_RABIT     
 Q9NS88         


  PROTEIN TITLES
   CCAA_MOUSE       Voltage-dependent P/Q-type calcium channel alpha-1A subunit 
   CCAA_RAT         Voltage-dependent P/Q-type calcium channel alpha-1A subunit 
   CCAA_HUMAN       Voltage-dependent P/Q-type calcium channel alpha-1A subunit 
   CCAA_RABIT       Voltage-dependent P/Q-type calcium channel alpha-1A subunit 
   Q9NS88           ALPHA1A-VOLTAGE-DEPENDENT CALCIUM CHANNEL - Homo sapiens (Hu

SCAN HISTORY SPTR40_18f 2 200 NSINGLE INITIAL MOTIF SETS PQVDCCALPHA11 Length of motif = 21 Motif number = 1 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif I - 1 PCODE ST INT DARRPWAGSQEAELSREGPYG CCAA_HUMAN 879 879 DARRAWPGSPERAPGREGPYG CCAA_MOUSE 811 811 DARRPWAGSQEAELSREGPYG CCAA_RABIT 881 881 DARRAWPSSPERAPGREGPYG CCAA_RAT 859 859 PQVDCCALPHA12 Length of motif = 19 Motif number = 2 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif II - 1 PCODE ST INT EGEAERGKAGDPHRRHVHR CCAA_HUMAN 918 18 DADTERAKAGDAPRRHTHR CCAA_MOUSE 851 19 EGEAERGKAGDPHRRHAHR CCAA_RABIT 920 18 DADPERAKAGDAPRRHTHR CCAA_RAT 899 19 PQVDCCALPHA13 Length of motif = 15 Motif number = 3 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif III - 1 PCODE ST INT KERRHRRRKENQGSG CCAA_HUMAN 1023 86 RERRHRRRKENQGSG CCAA_MOUSE 932 62 RERRHRRRKDTQGSG CCAA_RABIT 1033 94 RERRHRRRKESQGSG CCAA_RAT 980 62 PQVDCCALPHA14 Length of motif = 22 Motif number = 4 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif IV - 1 PCODE ST INT PDPLPKKEEEKKEEEEDDRGED CCAA_HUMAN 1192 154 PDPLPKKEEEKKEEEEADPGED CCAA_MOUSE 1095 148 PDPLPKKEDEKKEEVDEGPGED CCAA_RABIT 1201 153 PDPLPKKEEEKKEEEEADPGED CCAA_RAT 1143 148 PQVDCCALPHA15 Length of motif = 15 Motif number = 5 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif V - 1 PCODE ST INT GIDVEDEDSDEDEFQ CCAA_HUMAN 1718 504 GIDGEDEDSDEDEFQ CCAA_MOUSE 1621 504 GIDMEDEDSDEDEFQ CCAA_RABIT 1727 504 GIDGEDEDSDEDEFQ CCAA_RAT 1669 504 FINAL MOTIF SETS PQVDCCALPHA11 Length of motif = 21 Motif number = 1 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif I - 2 PCODE ST INT DARRAWPGSPERAPGREGPYG CCAA_MOUSE 811 811 DARRAWPSSPERAPGREGPYG CCAA_RAT 859 859 DARRPWAGSQEAELSREGPYG CCAA_HUMAN 879 879 DARRPWAGSQEAELSREGPYG CCAA_RABIT 881 881 DARRPWAGSQEAELSREDPYG Q9NS88 878 878 PQVDCCALPHA12 Length of motif = 19 Motif number = 2 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif II - 2 PCODE ST INT DADTERAKAGDAPRRHTHR CCAA_MOUSE 851 19 DADPERAKAGDAPRRHTHR CCAA_RAT 899 19 EGEAERGKAGDPHRRHVHR CCAA_HUMAN 918 18 EGEAERGKAGDPHRRHAHR CCAA_RABIT 920 18 EGEAERGKAGDPHRRHVHR Q9NS88 917 18 PQVDCCALPHA13 Length of motif = 15 Motif number = 3 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif III - 2 PCODE ST INT RERRHRRRKENQGSG CCAA_MOUSE 932 62 RERRHRRRKESQGSG CCAA_RAT 980 62 KERRHRRRKENQGSG CCAA_HUMAN 1023 86 RERRHRRRKDTQGSG CCAA_RABIT 1033 94 KERRHRRRKENQGSG Q9NS88 1022 86 PQVDCCALPHA14 Length of motif = 22 Motif number = 4 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif IV - 2 PCODE ST INT PDPLPKKEEEKKEEEEADPGED CCAA_MOUSE 1095 148 PDPLPKKEEEKKEEEEADPGED CCAA_RAT 1143 148 PDPLPKKEEEKKEEEEDDRGED CCAA_HUMAN 1192 154 PDPLPKKEDEKKEEVDEGPGED CCAA_RABIT 1201 153 PDPLPKKEEEKKEEEEDDRGED Q9NS88 1191 154 PQVDCCALPHA15 Length of motif = 15 Motif number = 5 P/Q-type voltage-dependent calcium channel alpha-1 subunit motif V - 2 PCODE ST INT GIDGEDEDSDEDEFQ CCAA_MOUSE 1621 504 GIDGEDEDSDEDEFQ CCAA_RAT 1669 504 GIDVEDEDSDEDEFQ CCAA_HUMAN 1718 504 GIDMEDEDSDEDEFQ CCAA_RABIT 1727 504 GIDVEDEDSDEDEFQ Q9NS88 1717 504

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