WORKLIST ENTRIES (1):

SKCHANNEL View alignment        Calcium-activated SK potassium channel signature
 Type of fingerprint: COMPOUND with 2  elements
Links:
   PRINTS; PR00169 KCHANNEL; PR01449 BKCHANNELA; PR01450 BKCHANNELB 

 Creation date 05-DEC-2000

   1. MILLER, C.
   An overview of the potassium channel family.
   GENOME BIOL. 1(4) 1-5 (2000).

   2. ASHCROFT, F.M.
   Ca2+-activated K+ channels.
   IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.125-133.

   3. VERGARA, C., LATORRE, R., MARRION, N.V. AND ADELMAN, J.P.
   Calcium-activated potassium channels.
   CURR.OPIN.NEUROBIOL. 8(3) 321-329 (1998).

   4. ISHII, T.M., MAYLIE, J. AND ADELMAN, J.P.
   Determinants of apamin and d-tubocurarine block in SK potassium channels.
   J.BIOL.CHEM. 272(37) 23195-23200 (1997).

   5. BOND, C.T., MAYLIE, J. AND ADELMAN, J.P.
   Small-conductance calcium-activated potassium channels.
   ANN.N.Y.ACAD.SCI. 868 370-378 (1999).

   6. CASTLE, N.A.
   Recent advances in the biology of small-conductance calcium-activated
   potassium channels.
   PERSPECTIVES DRUG DISCOVERY DESIGN 16 131-154 (1999).

   Potassium ion (K+) channels are a structurally diverse group of proteins
   that facilitate the flow of K+ ions across cell membranes. They are
   ubiquitous, being present in virtually all cell types. Activation of K+
   channels tends to hyperpolarise cells, reducing the membrane's electrical
   resistance, dampening nervous activity. In eukaryotic cells, K+ channels
   are involved in neural signalling and generation of the cardiac rhythm, and
   act as effectors in signal transduction pathways involving G protein-
   coupled receptors (GPCRs). In prokaryotic cells, they play a role in the
   maintenance of ionic homeostasis [1].
  
   Structurally, calcium (Ca2+) activated channels belong to the subfamily of
   K+ channels whose subunits contain 6 transmembrane (TM) domains: these are
   the voltage-gated K+ (Kv) channels, the KCNQ channels, the EAG-like K+ 
   channels and 3 kinds of Ca2+-activated K+ channel (BK, IK and SK) [2]. All
   K+ channels share a characteristic sequence feature: a TMxTVGYG motif that
   resides between the 2 C-terminal membrane-spanning helices, and forms
   the K+-selective pore domain [1].
   
   Ca2+-activated K+ channels are a diverse group of channels that are
   activated by an increase in intracellular Ca2+ concentration. They are
   found in the majority of nerve cells, where they modulate cell excitability
   and action potential. Three types of Ca2+-activated K+ channel have been
   characterised, termed small-conductance (SK), intermediate conductance (IK)
   and large conductance (BK) respectively [2-3].
   
   SK channels are thought to play an important role in the functioning of
   all excitable tissues. To date, 3 subtypes (designated SK1-SK3) have been
   cloned, each of which possesses a different tissue expression profile: SK1
   channels are expressed in the heart; SK2 channels are found in the adrenal
   gland; and SK3 channels are known to be present in skeletal muscle.
  
   Although SK channels have been classified as belonging to the 6TM domain
   voltage-gated K+ channel family, they show little or no sequence similarity
   to other family members. The fourth TM domain resembles the S4 voltage
   sensor domain of Kv channels, since it contains 3 positively charged 
   residues. However, despite similarity to the Kv voltage-sensory motif, SK 
   channel activation is not voltage sensitive.
   
   SKCHANNEL is a 2-element fingerprint that provides a signature for the
   calcium-activated SK potassium channels. The fingerprint was derived from 
   an initial alignment of 2 sequences: the motifs were drawn from conserved
   regions within the N-terminal portion of the alignment, focusing on those
   sections that characterise the SK potassium channels but distinguish them
   from other members of the K+ channel superfamily. Three iterations on
   SPTR39_14f were required to reach convergence, at which point a true set
   comprising 7 sequences was identified.

  SUMMARY INFORMATION
      7 codes involving  2 elements

   COMPOSITE FINGERPRINT INDEX
  
    2|   7    7  
   --+-----------
     |   1    2  

True positives..
 P70605         Q9UGI6         P70604         Q9PTS9         
 O43517         P70606         Q92952         


  PROTEIN TITLES
   P70605           CALCIUM-ACTIVATED POTASSIUM CHANNEL RSK3 - Rattus norvegicus
   Q9UGI6           SK3 PROTEIN - Homo sapiens (Human).
   P70604           CALCIUM-ACTIVATED POTASSIUM CHANNEL RSK2 - Rattus norvegicus
   Q9PTS9           SMALL-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNEL - Gall
   O43517           CALCIUM-ACTIVATED POTASSIUM CHANNEL - Homo sapiens (Human).
   P70606           CALCIUM-ACTIVATED POTASSIUM CHANNEL RSK1 - Rattus norvegicus
   Q92952           CALCIUM-ACTIVATED POTASSIUM CHANNEL HSK1 - Homo sapiens (Hum

SCAN HISTORY SPTR39_14f 3 100 NSINGLE INITIAL MOTIF SETS SKCHANNEL1 Length of motif = 21 Motif number = 1 Calcium-activated SK potassium channel motif I - 1 PCODE ST INT RLGHRRALFEKRKRLSDYALI P70606 88 88 KLGHRRALFEKRKRLSDYALI P70604 121 121 SKCHANNEL2 Length of motif = 19 Motif number = 2 Calcium-activated SK potassium channel motif II - 1 PCODE ST INT ELAVCAIHPVPGHYRFTWT P70606 188 79 EILVCAIHPIPGNYTFTWT P70604 221 79 FINAL MOTIF SETS SKCHANNEL1 Length of motif = 21 Motif number = 1 Calcium-activated SK potassium channel motif I - 3 PCODE ST INT KLGHRRALFEKRKRLSDYALI P70605 270 270 KLGHRRALFEKRKRLSDYALI Q9UGI6 274 274 KLGHRRALFEKRKRLSDYALI P70604 121 121 KLGHRRALFEKRKRLSDYALI Q9PTS9 94 94 KLGHRRAPFEKRKRLSDYALI O43517 269 269 RLGHRRALFEKRKRLSDYALI P70606 88 88 RLGHRRALFEKRKRLSDYALI Q92952 110 110 SKCHANNEL2 Length of motif = 19 Motif number = 2 Calcium-activated SK potassium channel motif II - 3 PCODE ST INT EMLVCAIHPIPGEYKFFWT P70605 370 79 EMLVCAIHPIPGEYKFFWT Q9UGI6 374 79 EILVCAIHPIPGNYTFTWT P70604 221 79 EILVCAIHPIPGNYTFTWT Q9PTS9 194 79 EMLVCAIHPIPGEYKFFWT O43517 369 79 ELAVCAIHPVPGHYRFTWT P70606 188 79 ELAVCAIHPVPGHYRFTWT Q92952 210 79

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