| 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).
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| 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.
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