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PR01586

Identifier
TWIKCHANNEL  [View Relations]  [View Alignment]  
Accession
PR01586
No. of Motifs
6
Creation Date
10-SEP-2001
Title
TWIK-1/TWIK-2 K+ channel family signature
Database References
PRINTS; PR00169 KCHANNEL; PR01333 2POREKCHANEL; PR01096 TWIK1CHANNEL
PRINTS; PR01587 TWIK2CHANNEL
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. 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.
 
TWIKCHANNEL is a 6-element fingerprint that provides a signature for the
TWIK K+ channel family. 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 channel proteins but distinguish them from related
two P-domain K+ channel sequences - motifs 1 and 2 lie in the first putative
TM domain; motif 3 is situated in the second TM domain; motif 4 is located
in the C-terminus of the second P-domain; and motifs 5 and 6 span the fourth
TM domain and the C-terminus respectively. Two iterations on SPTR39.22_17.3f
were required to reach convergence, at which point a true set comprising 6
sequences was identified. Several partial matches were also found, all of
which are members of the TWIK K+ channel family that fail to make
significant matches with one or more motifs. 
Summary Information
   6 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
2 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
6666666
5000000
4000000
3000222
2001100
123456
True Positives
CIW6_HUMAN    O00180        O08581        Q99L99        
Q9ERU5 Q9Z2T2
True Positive Partials
Codes involving 3 elements
Q9ERU4 Q9HB47
Codes involving 2 elements
Q9NEV3
Sequence Titles
CIW6_HUMAN  POTASSIUM CHANNEL SUBFAMILY K MEMBER 6 (INWARD RECTIFYING POTASSIUM CHANNEL PROTEIN TWIK-2) (TWIK-ORIGINATED SIMILARITY SEQUENCE) - Homo sapiens (Human). 
O00180 POTASSIUM CHANNEL KCNO1 - HOMO SAPIENS (HUMAN).
O08581 POTASSIUM INWARDLY-RECTIFYING CHANNEL, SUBFAMILY K, MEMBER 1 (TWIK-1 K+ CHANNEL)
Q99L99 POTASSIUM CHANNEL, SUBFAMILY K, MEMBER 1 - Mus musculus (Mouse).
Q9ERU5 2P DOMAIN K+ CHANNEL TWIK-2 - Rattus norvegicus (Rat).
Q9Z2T2 PUTATIVE POTASSIUM CHANNEL TWIK - Rattus norvegicus (Rat).

Q9ERU4 2P DOMAIN K+ CHANNEL TWIK-2 - Rattus norvegicus (Rat).
Q9HB47 2P DOMAIN K+ CHANNEL TWIK-2 - Homo sapiens (Human).

Q9NEV3 Y39B6B.F PROTEIN - Caenorhabditis elegans.
Scan History
SPTR39.22_17.3f 2  90   NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
CLSEPQLEQFLGR O08581 69 69 -
CLSEQQLEQFLGR O00180 69 69 -
CVAAPALDAFVER CIW6_HUMAN 53 53 -
CVAAHALDAFVER Q9ERU5 53 53 -

Motif 2 width=17
Element Seqn Id St Int Rpt
LEASNYGVSVLSNASGN O08581 83 1 -
LEASNYGVSVLSNASGN O00180 83 1 -
LAAGRLGRVVLANASGS CIW6_HUMAN 67 1 -
LAAGRLGRAVLANASGP Q9ERU5 67 1 -

Motif 3 width=13
Element Seqn Id St Int Rpt
PFTLLFLTALVQR O08581 143 43 -
PFTLLFLTAVVQR O00180 143 43 -
PTTMLLLTASAQR CIW6_HUMAN 132 48 -
PITMLLLTASAQR Q9ERU5 132 48 -

Motif 4 width=14
Element Seqn Id St Int Rpt
PGEGYNQKFRELYK O08581 233 77 -
PGEGYNQKFRELYK O00180 233 77 -
PGEAPGQPYRALYK CIW6_HUMAN 222 77 -
PGEAPGQPYRSLYK Q9ERU5 222 77 -

Motif 5 width=14
Element Seqn Id St Int Rpt
TCYLLLGLITMLVV O08581 250 3 -
TCYLLLGLIAMLVV O00180 250 3 -
TVYLFLGLVAMVLV CIW6_HUMAN 239 3 -
TAYLFLGLVAMVLV Q9ERU5 239 3 -

Motif 6 width=19
Element Seqn Id St Int Rpt
ETFCELHELKKFRKMFYVK O08581 265 1 -
ETFCELHELKKFRKMFYVK O00180 265 1 -
QTFRHVSDLHGLTELILLP CIW6_HUMAN 254 1 -
QTFRRVSDLHGLTELILLP Q9ERU5 254 1 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
CLSEPQLEQFLGR Q99L99 69 69 -
CLSEPQLEQFLGR Q9Z2T2 69 69 -
CLSEPQLEQFLGR O08581 69 69 -
CLSEQQLEQFLGR O00180 69 69 -
CVAAPALDAFVER CIW6_HUMAN 53 53 -
CVAAHALDAFVER Q9ERU5 53 53 -

Motif 2 width=17
Element Seqn Id St Int Rpt
LEASNYGVSVLSNASGN Q99L99 83 1 -
LEASNYGVSVLSNASGN Q9Z2T2 83 1 -
LEASNYGVSVLSNASGN O08581 83 1 -
LEASNYGVSVLSNASGN O00180 83 1 -
LAAGRLGRVVLANASGS CIW6_HUMAN 67 1 -
LAAGRLGRAVLANASGP Q9ERU5 67 1 -

Motif 3 width=13
Element Seqn Id St Int Rpt
PFTLLFLTAVVQR Q99L99 143 43 -
PFTLLFLTAVVQR Q9Z2T2 143 43 -
PFTLLFLTALVQR O08581 143 43 -
PFTLLFLTAVVQR O00180 143 43 -
PTTMLLLTASAQR CIW6_HUMAN 132 48 -
PITMLLLTASAQR Q9ERU5 132 48 -

Motif 4 width=14
Element Seqn Id St Int Rpt
PGEGYNQKFRELYK Q99L99 233 77 -
PGEGYNQKFRELYK Q9Z2T2 233 77 -
PGEGYNQKFRELYK O08581 233 77 -
PGEGYNQKFRELYK O00180 233 77 -
PGEAPGQPYRALYK CIW6_HUMAN 222 77 -
PGEAPGQPYRSLYK Q9ERU5 222 77 -

Motif 5 width=14
Element Seqn Id St Int Rpt
TCYLLLGLIAMLVV Q99L99 250 3 -
TCYLLLGLIAMLVV Q9Z2T2 250 3 -
TCYLLLGLITMLVV O08581 250 3 -
TCYLLLGLIAMLVV O00180 250 3 -
TVYLFLGLVAMVLV CIW6_HUMAN 239 3 -
TAYLFLGLVAMVLV Q9ERU5 239 3 -

Motif 6 width=19
Element Seqn Id St Int Rpt
ETFCELHELKKFRKMFYVK Q99L99 265 1 -
ETFCELHELKKFRKMFYVK Q9Z2T2 265 1 -
ETFCELHELKKFRKMFYVK O08581 265 1 -
ETFCELHELKKFRKMFYVK O00180 265 1 -
QTFRHVSDLHGLTELILLP CIW6_HUMAN 254 1 -
QTFRRVSDLHGLTELILLP Q9ERU5 254 1 -