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PR01584

Identifier
TASK1CHANNEL  [View Relations]  [View Alignment]  
Accession
PR01584
No. of Motifs
4
Creation Date
10-SEP-2001
Title
TASK-1 K+ channel signature
Database References
PRINTS; PR00169 KCHANNEL; PR01333 2POREKCHANEL; PR01095 TASKCHANNEL
Literature References
1. KETCHUM, K.A., JOINER, W.J., SELLERS, A.J., KACZMAREK, L.K. AND
GOLDSTEIN, S.A.N.
A new family of outwardly rectifying potassium channel proteins with two
pore domains in tandem.
NATURE 376 690-695 (1995).
 
2. GOLDSTEIN, S.A.N., PRICE, L.A., ROSENTHAL, D.N. AND PAUSCH, M.H.
ORK1, a potassium-selective leak channel with two pore domains cloned from
Drosophila melanogaster by expression in Saccharomyces cerevisiae.
PROC.NATL.ACAD.SCI.U.S.A. 93 13256-13261 (1996).
 
3. FINK, M. DUPRAT, F., LESAGE, F., REYES, R., ROMEY, G., HEURTEAUX, C. AND
LAZDUNSKI, M.
Cloning, functional expression and brain localization of a novel
unconventional outward rectifier K+ channel.
EMBO J. 15 6854-6862 (1996).
 
4. LESAGE, F., GUILLEMARE, E., FINK, M., DUPRAT, F., LAZDUNSKI, M., ROMEY,
G. AND BARHANIN, J.
TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with novel
structure.
EMBO J. 15 1004-1011 (1996).
 
5. DUPRAT, F., LESAGE, F., FINK, M., REYES, R., HEURTEAUX, C. AND
LAZDUNSKI, M.
TASK, a human background K+ channel to sense external pH variations near
physiological pH.
EMBO J. 16 5464-5471 (1997).
 
6. FINK, M., LESAGE, F., DUPRAT, F., HEURTEAUX, C., REYES, R., FOSSET, M.
AND LAZDUNSKI, M.
A neuronal two P domain K+ channel stimulated by arachidonic acid and
polyunsaturated fatty acids.
EMBO J. 17 3297-3308 (1998).
 
7. PATEL, A.J. AND HONORE, E.
Properties and modulation of mammalian 2P-domain K+ channels.
TRENDS NEUROSCI. 24(6) 339-346 (2001).
 
8. LESAGE, F. AND LAZDUNSKI, M.
Molecular and functional properties of two pore-domain potassium channels.
AM.J.PHYSIOL. RENAL PHYSIOL. 279(5) 793-801 (2000).

Documentation
Potassium (K+) channels play a key role in many cellular functions, in both
excitable and non-excitable tissues. Among the ion channels, they form the
largest family in terms of both structure and function. K+ channel subunits
contain a conserved pore-forming motif, the P-domain, which is considered to
be an essential element of the aqueous K+-selective pore. Shaker-type and
Kir K+ channel subunits both contain a single P-domain, and four such
subunits are thought to associate to form a multimer, together with 
associated auxillary (regulatory) subunits. Recently, a new class of K+ 
channel subunits was cloned, which is clearly distinct from the Shaker and
Kir families; the new class contains not one but two P-domains in each 
subunit, and evidence suggests a complete channel may be formed by the 
dimerisation of two such subunits.
 
The first member of this family (TOK1) cloned from S.cerevisiae [1] was
predicted to have eight potential transmembrane (TM) helices. However,
subsequently-cloned two P-domain family members from Drosophila and
mammalian species are predicted to have only four TM segments. They are
usually referred to as TWIK-related channels (Tandem of P-domains in a 
Weakly Inward rectifying K+ channel) [2-6]. Functional characterisation of
these channels has revealed a diversity of properties in that they may show 
inward or outward rectification, their activity may be modulated in 
different directions by protein phosphorylation, and their sensitivity to
changes in intracellular or extracellular pH varies. Despite these disparate
properties, they are all thought to share the same topology of four TM 
segments, including two P-domains. That TWIK-related K+ channels all produce
instantaneous and non-inactivating K+ currents, which do not display a
voltage-dependent activation threshold, suggests that they are background 
(leak) K+ channels involved in the generation and modulation of the resting
membrane potential in various cell types. Further studies have revealed that
they may be found in many species, including: plants, invertebrates and 
mammals.
 
The TASK (TWIK-related acid-sensitive K+ channel) family contains five
members (TASK1-5), which share no more than 54% amino acid identity. These
form functional K+ channels in various cell types and encode background
K+ channels, thereby helping to set the resting membrane potential. All
members are very sensitive to variations in extracellular pH in the
physiological range, changing from fully-open to closed in approximately
0.5pH units around pH7.4. Thus, they may well constitute biological sensors
of external pH variations [7].
 
TASK-1 was the first member of the TASK family to be cloned. It is widely
distributed, being particularly abundant in the pancreas and placenta, but
is also found in the brain, heart, lung and kidney. In addition to the 
maintenance of the resting membrane potential, it is also involved in K+
transport associated with recycling/secretion and the modulation of
electrical activity of excitable cells [8].
 
TASK1CHANNEL is a 4-element fingerprint that provides a signature for the
TASK-1 K+ channel. The fingerprint was derived from an initial alignment of
3 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise 
TASK-1 channel proteins but distinguish them from related TASK family 
members - motif 1 is located in the second putative TM domain; motif 2 is 
situated in the C-terminus of the second P-domain; and motifs 3 and 4 span
the C-terminus. Two iterations on SPTR39.22_17.3f were required to reach
convergence, at which point a true set comprising 5 sequences was identified.
Summary Information
5 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
45555
30000
20000
1234
True Positives
O14649        O35111        O54912        Q9ESM4        
Q9ESM5
Sequence Titles
O14649      TWIK-RELATED ACID-SENSITIVE K+ CHANNEL - HOMO SAPIENS (HUMAN). 
O35111 CTBAK - MUS MUSCULUS (MOUSE).
O54912 TWIK-RELATED ACID-SENSITIVE K+ CHANNEL - RATTUS NORVEGICUS (RAT).
Q9ESM4 TWIK-RELATED ACID-SENSITIVE K+ CHANNEL SPRICE VARIANT (TASK1C) - Rattus norvegicus (Rat).
Q9ESM5 TASK1 SPLICE BVARIANT (TASK1B) - Rattus norvegicus (Rat).
Scan History
SPTR39.22_17.3f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
RHAEVSMANMVLIG O35111 150 150 -
RHAEVSMANMVLIG O54912 150 150 -
RRADVSMANMVLIG O14649 150 150 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KDQALQTQPQYVA O35111 210 46 -
KDQALQTQPQYVA O54912 210 46 -
KDQALQTQPQYVA O14649 210 46 -

Motif 3 width=16
Element Seqn Id St Int Rpt
HRALLTHNGQAVGLGG O35111 260 37 -
HRALLTHNGQAGGLGG O54912 260 37 -
HRALLTRNGQAGGGGG O14649 260 37 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NVYAEVLHFQSMC O35111 313 37 -
NVYAEMLHFQSMC O54912 315 39 -
NVYAEVLHFQSMC O14649 298 22 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
RHAEVSMANMVLIG O35111 150 150 -
RHAEVSMANMVLIG O54912 150 150 -
RHAEVSMANMVLIG Q9ESM4 40 40 -
RHAEVSMANMVLIG Q9ESM5 131 131 -
RRADVSMANMVLIG O14649 150 150 -

Motif 2 width=13
Element Seqn Id St Int Rpt
KDQALQTQPQYVA O35111 210 46 -
KDQALQTQPQYVA O54912 210 46 -
KDQALQTQPQYVA Q9ESM4 100 46 -
KDQALQTQPQYVA Q9ESM5 191 46 -
KDQALQTQPQYVA O14649 210 46 -

Motif 3 width=16
Element Seqn Id St Int Rpt
HRALLTHNGQAVGLGG O35111 260 37 -
HRALLTHNGQAGGLGG O54912 260 37 -
HRALLTHNGQAGGLGG Q9ESM4 150 37 -
HRALLTHNGQAGGLGG Q9ESM5 241 37 -
HRALLTRNGQAGGGGG O14649 260 37 -

Motif 4 width=13
Element Seqn Id St Int Rpt
NVYAEVLHFQSMC O35111 313 37 -
NVYAEMLHFQSMC O54912 315 39 -
NVYAEMLHFQSMC Q9ESM4 205 39 -
NVYAEMLHFQSMC Q9ESM5 296 39 -
NVYAEVLHFQSMC O14649 298 22 -