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PR01588

Identifier
THIKCHANNEL  [View Relations]  [View Alignment]  
Accession
PR01588
No. of Motifs
7
Creation Date
10-SEP-2001
Title
THIK K+ channel signature
Database References
PRINTS; PR00169 KCHANNEL; PR01333 2POREKCHANEL
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. RAJAN, S., WISCHMEYER, E., KARSCHIN, C., PREISIG-MULLER, R., GRZESCHIK,
K.H., DAUT, J., KARSCHIN, A. AND DERST, C.
THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels.
J.BIOL.CHEM. 276(10) 7302-7311 (2001).

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 THIK (Tandem pore-domain Halothane Inhibited K+ channel) family
contains two members: THIK-1 and THIK-2. Both proteins were first isolated
from rat and have subsequently been found in human. THIK-1 is expressed
ubiquitously and is activated by arachidonic acid and inhibited by the
volatile anaesthetic halothane. The second member, THIK-2, shares 58% amino
acid identity with THIK-1, but is not functionally expressed. THIK-2 is 
strongly expressed in several tissues, and is particularly abundant in the
brain [7].
 
THIKCHANNEL is a 7-element fingerprint that provides a signature for the
THIK 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
THIK channel proteins but distinguish them from related two P-domain K+
channel sequences - motif 1 is situated in the first putative TM domain; 
motifs 2 and 3 are located in the N-terminus of the first P-domain; motif 4
lies in the C-terminus of the first P-domain; motif 5 spans the N-terminus
of the second P-domain; motif 6 lies in the fourth TM domain; and motif 7
resides 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  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
74444444
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
Q9ERS0        Q9ERS1        Q9HB14        Q9HB15        
Sequence Titles
Q9ERS0      TANDEM PORE DOMAIN POTASSIUM CHANNEL THIK-1 - Rattus norvegicus (Rat). 
Q9ERS1 TANDEM PORE DOMAIN POTASSIUM CHANNEL THIK-2 - Rattus norvegicus (Rat).
Q9HB14 TANDEM PORE DOMAIN POTASSIUM CHANNEL THIK-1 - Homo sapiens (Human).
Q9HB15 TANDEM PORE DOMAIN POTASSIUM CHANNEL THIK-2 - Homo sapiens (Human).
Scan History
SPTR39.22_17.3f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
LNEDTGRFVLLAALIG Q9ERS1 32 32 -
LNEDTGRFVLLAALIG Q9HB15 32 32 -
LNEDNARFLLLAALIV Q9HB14 13 13 -
LNEDNARFLLLAGLIL Q9ERS0 13 13 -

Motif 2 width=13
Element Seqn Id St Int Rpt
EPELRAFLRHYEA Q9ERS1 87 39 -
EPELRAFLRHYEA Q9HB15 87 39 -
RDELRGFLRHYEE Q9HB14 68 39 -
REELRGFLRHYEE Q9ERS0 68 39 -

Motif 3 width=13
Element Seqn Id St Int Rpt
LAAGVRADALRPR Q9ERS1 101 1 -
LAAGVRADALRPR Q9HB15 101 1 -
TRAGIRVDNVRPR Q9HB14 82 1 -
TKAGIRMDSVRPR Q9ERS0 82 1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GCAGTILFFNLFLER Q9ERS1 153 39 -
GCAGTILFFNLFLER Q9HB15 153 39 -
GCSSTILFFNLFLER Q9HB14 134 39 -
GCASTILFFNLFLER Q9ERS0 134 39 -

Motif 5 width=14
Element Seqn Id St Int Rpt
SAMYTSVEGWDYVD Q9ERS1 232 64 -
SAMYTSVEGWDYVD Q9HB15 232 64 -
SAMYTPIEGWSYFD Q9HB14 213 64 -
SALYTTMEGWSYFD Q9ERS0 213 64 -

Motif 6 width=13
Element Seqn Id St Int Rpt
NFLFILLGVCCIY Q9ERS1 280 34 -
NFLFILLGVCCIY Q9HB15 280 34 -
NFVFILMGVCCIY Q9HB14 261 34 -
NFFFILMGVCCIY Q9ERS0 261 34 -

Motif 7 width=13
Element Seqn Id St Int Rpt
SLALLQKQLSETA Q9ERS1 381 88 -
SLALLQKQLSETA Q9HB15 381 88 -
SLAILQKQLSEMA Q9HB14 359 85 -
SLAILQKQLSEMA Q9ERS0 356 82 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
LNEDTGRFVLLAALIG Q9ERS1 32 32 -
LNEDTGRFVLLAALIG Q9HB15 32 32 -
LNEDNARFLLLAALIV Q9HB14 13 13 -
LNEDNARFLLLAGLIL Q9ERS0 13 13 -

Motif 2 width=13
Element Seqn Id St Int Rpt
EPELRAFLRHYEA Q9ERS1 87 39 -
EPELRAFLRHYEA Q9HB15 87 39 -
RDELRGFLRHYEE Q9HB14 68 39 -
REELRGFLRHYEE Q9ERS0 68 39 -

Motif 3 width=13
Element Seqn Id St Int Rpt
LAAGVRADALRPR Q9ERS1 101 1 -
LAAGVRADALRPR Q9HB15 101 1 -
TRAGIRVDNVRPR Q9HB14 82 1 -
TKAGIRMDSVRPR Q9ERS0 82 1 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GCAGTILFFNLFLER Q9ERS1 153 39 -
GCAGTILFFNLFLER Q9HB15 153 39 -
GCSSTILFFNLFLER Q9HB14 134 39 -
GCASTILFFNLFLER Q9ERS0 134 39 -

Motif 5 width=14
Element Seqn Id St Int Rpt
SAMYTSVEGWDYVD Q9ERS1 232 64 -
SAMYTSVEGWDYVD Q9HB15 232 64 -
SAMYTPIEGWSYFD Q9HB14 213 64 -
SALYTTMEGWSYFD Q9ERS0 213 64 -

Motif 6 width=13
Element Seqn Id St Int Rpt
NFLFILLGVCCIY Q9ERS1 280 34 -
NFLFILLGVCCIY Q9HB15 280 34 -
NFVFILMGVCCIY Q9HB14 261 34 -
NFFFILMGVCCIY Q9ERS0 261 34 -

Motif 7 width=13
Element Seqn Id St Int Rpt
SLALLQKQLSETA Q9ERS1 381 88 -
SLALLQKQLSETA Q9HB15 381 88 -
SLAILQKQLSEMA Q9HB14 359 85 -
SLAILQKQLSEMA Q9ERS0 356 82 -