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PR01587

Identifier
TWIK2CHANNEL  [View Relations]  [View Alignment]  
Accession
PR01587
No. of Motifs
5
Creation Date
10-SEP-2001
Title
TWIK-2 K+ channel signature
Database References
PRINTS; PR00169 KCHANNEL; PR01333 2POREKCHANEL; PR01586 TWIKCHANNEL
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. CHAVEZ, R.A., GRAY, A.T., ZHAO, B.B., KINDLER, C.H., MAZUREK, M.J.,
MEHTA, Y., FORSAYETH, J.R. AND YOST, C.S.
TWIK-2, a new weak inward rectifying member of the tandem pore domain
potassium channel family.
J.BIOL.CHEM. 274 7887-7892 (1999).
 
8. PATEL, A.J., MAINGRET, F., MAGNONE, V., FOSSET, M., LAZDUNSKI, M. AND
HONORE, E.
TWIK-2, an inactivating 2P-domain K+ channel.
J.BIOL.CHEM. 275(37) 28722-28730 (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.
 
TWIK family members (TWIK-1 and TWIK-2) produce constitutive K+ currents of
weak amplitude [4,7]. They are present in a variety of tissues, including
brain and cells of the immune system. Together with their functional 
properties, their wide distribution suggests that these channels may be
involved in the control of background K+ conductances in many cell types.
 
TWIK-2 is expressed in the gastrointestinal tract, as well as the brain 
and immune system. The transient and delayed activities of TWIK-2 suggests
that it may play an important role in cell electrogenesis [7,8]. 
Pharmacologically, TWIK-2 channels are distinct from TWIK-1 channels in 
terms of their response to quinidine and barium. They are inhibited by 
intracellular, but not extracellular, acidification [7].
 
TWIK2CHANNEL is a 5-element fingerprint that provides a signature for the
TWIK-2 K+ channel. The fingerprint was derived from an initial alignment of
4 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise
TWIK-2 channel proteins but distinguish them from closely related TWIK
family members - motif 1 is located in the N-terminus of the first P-
domain; motif 2 spans the third putative TM domain; motif 3 is situated in
the fourth TM domain; and motifs 4 and 5 lie in the C-terminus. A single
iteration on SPTR39.22_17.3f was required to reach convergence, no further
sequences being identified beyond the starting set.
Summary Information
4 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
544444
400000
300000
200000
12345
True Positives
CIW6_HUMAN    Q9ERU4        Q9ERU5        Q9HB47        
Sequence Titles
CIW6_HUMAN  POTASSIUM CHANNEL SUBFAMILY K MEMBER 6 (INWARD RECTIFYING POTASSIUM CHANNEL PROTEIN TWIK-2) (TWIK-ORIGINATED SIMILARITY SEQUENCE) - Homo sapiens (Human). 
Q9ERU4 2P DOMAIN K+ CHANNEL TWIK-2 - Rattus norvegicus (Rat).
Q9ERU5 2P DOMAIN K+ CHANNEL TWIK-2 - Rattus norvegicus (Rat).
Q9HB47 2P DOMAIN K+ CHANNEL TWIK-2 - Homo sapiens (Human).
Scan History
SPTR39.22_17.3f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
PLSWLSMRWGWDPRR CIW6_HUMAN 153 153 -
PLSWLSMRWGWDPRR Q9HB47 19 19 -
PLSWLSLRWGWHPQR Q9ERU5 153 153 -
PLSWLSLRWGWHPQR Q9ERU4 19 19 -

Motif 2 width=11
Element Seqn Id St Int Rpt
WHLVALLGVVV CIW6_HUMAN 171 3 -
WHLVALLGVVV Q9HB47 37 3 -
WHLVALLMVIV Q9ERU5 171 3 -
WHLVALLMVIV Q9ERU4 37 3 -

Motif 3 width=13
Element Seqn Id St Int Rpt
YLFLGLVAMVLVL CIW6_HUMAN 241 59 -
YLFLGLVAMVLVL Q9HB47 107 59 -
YLFLGLVAMVLVL Q9ERU5 241 59 -
YLFLGLVAMVLVL Q9ERU4 107 59 -

Motif 4 width=17
Element Seqn Id St Int Rpt
TFRHVSDLHGLTELILL CIW6_HUMAN 255 1 -
TFRHVSDLHGLTELILL Q9HB47 121 1 -
TFRRVSDLHGLTELILL Q9ERU5 255 1 -
TFRRVSDLHGLTELILL Q9ERU4 121 1 -

Motif 5 width=14
Element Seqn Id St Int Rpt
DEDDRVDILGPQPE CIW6_HUMAN 282 10 -
DEDDRVDILGPQPE Q9HB47 148 10 -
DEDDQVDILDARTD Q9ERU5 282 10 -
DEDDQVDILDARTD Q9ERU4 148 10 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
PLSWLSMRWGWDPRR CIW6_HUMAN 153 153 -
PLSWLSMRWGWDPRR Q9HB47 19 19 -
PLSWLSLRWGWHPQR Q9ERU5 153 153 -
PLSWLSLRWGWHPQR Q9ERU4 19 19 -

Motif 2 width=11
Element Seqn Id St Int Rpt
WHLVALLGVVV CIW6_HUMAN 171 3 -
WHLVALLGVVV Q9HB47 37 3 -
WHLVALLMVIV Q9ERU5 171 3 -
WHLVALLMVIV Q9ERU4 37 3 -

Motif 3 width=13
Element Seqn Id St Int Rpt
YLFLGLVAMVLVL CIW6_HUMAN 241 59 -
YLFLGLVAMVLVL Q9HB47 107 59 -
YLFLGLVAMVLVL Q9ERU5 241 59 -
YLFLGLVAMVLVL Q9ERU4 107 59 -

Motif 4 width=17
Element Seqn Id St Int Rpt
TFRHVSDLHGLTELILL CIW6_HUMAN 255 1 -
TFRHVSDLHGLTELILL Q9HB47 121 1 -
TFRRVSDLHGLTELILL Q9ERU5 255 1 -
TFRRVSDLHGLTELILL Q9ERU4 121 1 -

Motif 5 width=14
Element Seqn Id St Int Rpt
DEDDRVDILGPQPE CIW6_HUMAN 282 10 -
DEDDRVDILGPQPE Q9HB47 148 10 -
DEDDQVDILDARTD Q9ERU5 282 10 -
DEDDQVDILDARTD Q9ERU4 148 10 -