| 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. MAINGRET, F., LAURITZEN, I., PATEL, A.J., HEURTEAUX, C., REYES, R.,
LESAGE, F., LAZDUNSKI, M. AND HONORE, E.
TREK-1 is a heat activated background K+ channel.
EMBO J. 19 2483-2491 (2000).
8. BANG, H., KIM, Y. AND KIM, D.
TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family.
J.BIOL.CHEM. 275(23) 17412-17419 (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 subunit 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], is
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.
TREK is a member of the TWIK-related (2-pore domain) K+ channel family
identifed in human tissues. It has two members, designate TREK-1 and TREK-2.
TREK-1 is distributed in neuronal, cardiac and smooth muscle cells, whereas
TREK-2 has been shown to be expressed in the cerebellum [7,8]. Both members
are known as mechano-sensitive and unsaturated fatty acid-activated K+
channels as they are opened by membrane stretch, cell swelling, shear
stress and polyunsaturated fatty acids, such as arachidonic acid [8].
TREKCHANNEL is a 12-element fingerprint that provides a signature for the
Trek K+ channel. The fingerprint was derived from an initial alignment of 4
sequences: the motifs were drawn from conserved regions spanning the full
alignment length: motif 1 resides in the N-terminus; motif 2 spans part of
the first putative TM domain; motifs 3, 4 and 5 span the loop between TM
domains 1 and 2; motif 6 spans TM domain 2; motif 7 resides in the loop
between TM domains 2 and 3; motif 8 lies in TM domain 3; motifs 9 and 10
span TM domain 4; and motifs 11 and 12 reside within the C-terminus. Two
iterations on SPTR39_15f were required to reach convergence, at which point
a true set comprising 4 sequences was identified. Two partial matches
were also found, Q9NYG8 and O88454, which are human and mouse TWIK-related
arachidonic acid-stimulated potassium channel TRAAK proteins that match
motifs 4, 6 and 10.
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