SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01499

Identifier
TREKCHANNEL  [View Relations]  [View Alignment]  
Accession
PR01499
No. of Motifs
12
Creation Date
26-FEB-2001
Title
Trek 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. 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).

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. 
Summary Information
   4 codes involving 12 elements
0 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
1 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
12444444444444
11000000000000
10000000000000
9000000000000
8000000000000
7000000000000
6000000000000
5000000000000
4000000000000
3000101000100
2000001000100
123456789101112
True Positives
O95069        P97438        Q9JIS4        Q9NRT2        
True Positive Partials
Codes involving 3 elements
Q9NYG8
Codes involving 2 elements
O88454
Sequence Titles
O95069      OUTWARD RECTIFYING POTASSIUM CHANNEL PROTEIN TREK-1 (TWO-PORE POTASSIUM CHANNEL TPKC1) (TREK-1 K+ CHANNEL SUBUNIT) - Homo sapiens (Human). 
P97438 OUTWARD RECTIFYING POTASSIUM CHANNEL PROTEIN TREK-1 (TWO-PORE POTASSIUM CHANNEL TPKC1) (TREK-1 K+ CHANNEL SUBUNIT) - Mus musculus (Mouse).
Q9JIS4 POTASSIUM CHANNEL TREK-2 - Rattus norvegicus (Rat).
Q9NRT2 TWO-PORE DOMAIN POTASSIUM CHANNEL TREK-1 - Homo sapiens (Human).

Q9NYG8 TANDEM PORE DOMAIN POTASSIUM CHANNEL TRAAK - Homo sapiens (Human).

O88454 TWIK-RELATED ARACHIDONIC ACID-STIMULATED POTASSIUM CHANNEL PROTEIN TRAAK - Mus musculus (Mouse).
Scan History
SPTR39_15f 2  40   NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MAAPDLLDPKSAAQ Q9NRT2 1 1 -
MAAPDLLDPKSAAQ P97438 1 1 -
VAAPDLLDPKSAAQ O95069 16 16 -
AAAPPVCQPKSATN Q9JIS4 22 22 -

Motif 2 width=18
Element Seqn Id St Int Rpt
TINVMKWKTVSTIFLVVV Q9NRT2 38 23 -
AINVMKWKTVSTIFLVVV P97438 38 23 -
TINVMKWKTVSTIFLVVV O95069 53 23 -
LQTVMKWKTVVAIFVVVV Q9JIS4 63 27 -

Motif 3 width=13
Element Seqn Id St Int Rpt
SQRTTIVIQKQTF Q9NRT2 75 19 -
SQRTTIVIQKQTF P97438 75 19 -
SQRTTIVIQKQTF O95069 90 19 -
SQKNTIALEKAEF Q9JIS4 100 19 -

Motif 4 width=19
Element Seqn Id St Int Rpt
SQHSCVNSTELDELIQQIV Q9NRT2 89 1 -
AQHACVNSTELDELIQQIV P97438 89 1 -
SQHSCVNSTELDELIQQIV O95069 104 1 -
RDHICVSPQELETLIQHAL Q9JIS4 114 1 -

Motif 5 width=13
Element Seqn Id St Int Rpt
PLGNTSNQISHWD Q9NRT2 116 8 -
PLGNSSNQVSHWD P97438 116 8 -
PLGNTSNQISHWD O95069 131 8 -
PVGNSSNSSSHWD Q9JIS4 141 8 -

Motif 6 width=20
Element Seqn Id St Int Rpt
GIPLFGFLLAGVGDQLGTIF Q9NRT2 166 37 -
GIPLFGFLLAGVGDQLGTIF P97438 166 37 -
GIPLFGFLLAGVGDQLGTIF O95069 181 37 -
GIPLFGFLLAGIGDQLGTIF Q9JIS4 191 37 -

Motif 7 width=20
Element Seqn Id St Int Rpt
GKGIAKVEDTFIKWNVSQTK Q9NRT2 186 0 -
GKGIAKVEDTFIKWNVSQTK P97438 186 0 -
GKGIAKVEDTFIKWNVSQTK O95069 201 0 -
GKSIARVEKVFRKKQVSQTK Q9JIS4 211 0 -

Motif 8 width=12
Element Seqn Id St Int Rpt
RIISTIIFILFG Q9NRT2 207 1 -
RIISTIIFILFG P97438 207 1 -
RIISTIIFILFG O95069 222 1 -
RVISTILFILAG Q9JIS4 232 1 -

Motif 9 width=16
Element Seqn Id St Int Rpt
SDIEYLDFYKPVVWFW Q9NRT2 262 43 -
SDIEYLDFYKPVVWFW P97438 262 43 -
SDIEYLDFYKPVVWFW O95069 277 43 -
AGINYREWYKPLVWFW Q9JIS4 288 44 -

Motif 10 width=12
Element Seqn Id St Int Rpt
YFAAVLSMIGDW Q9NRT2 284 6 -
YFAAVLSMIGDW P97438 284 6 -
YFAAVLSMIGRL O95069 299 6 -
YFAAVLSMIGDW Q9JIS4 310 6 -

Motif 11 width=17
Element Seqn Id St Int Rpt
RVISKKTKEEVGEFRAH Q9NRT2 297 1 -
RVISKKTKEEVGEFRAH P97438 297 1 -
RVISKKTKEEVGEFRAH O95069 312 1 -
RVLSKKTKEEVGEIKAH Q9JIS4 323 1 -

Motif 12 width=15
Element Seqn Id St Int Rpt
SVEIYDKFQRATSIK Q9NRT2 333 19 -
SVEIYDKFQRATSVK P97438 333 19 -
SVEIYDKFQRATSIK O95069 348 19 -
SVEIHDKLQRAATIR Q9JIS4 359 19 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
MAAPDLLDPKSAAQ Q9NRT2 1 1 -
MAAPDLLDPKSAAQ P97438 1 1 -
VAAPDLLDPKSAAQ O95069 16 16 -
AAAPPVCQPKSATN Q9JIS4 22 22 -

Motif 2 width=18
Element Seqn Id St Int Rpt
TINVMKWKTVSTIFLVVV Q9NRT2 38 23 -
AINVMKWKTVSTIFLVVV P97438 38 23 -
TINVMKWKTVSTIFLVVV O95069 53 23 -
LQTVMKWKTVVAIFVVVV Q9JIS4 63 27 -

Motif 3 width=13
Element Seqn Id St Int Rpt
SQRTTIVIQKQTF Q9NRT2 75 19 -
SQRTTIVIQKQTF P97438 75 19 -
SQRTTIVIQKQTF O95069 90 19 -
SQKNTIALEKAEF Q9JIS4 100 19 -

Motif 4 width=19
Element Seqn Id St Int Rpt
SQHSCVNSTELDELIQQIV Q9NRT2 89 1 -
AQHACVNSTELDELIQQIV P97438 89 1 -
SQHSCVNSTELDELIQQIV O95069 104 1 -
RDHICVSPQELETLIQHAL Q9JIS4 114 1 -

Motif 5 width=13
Element Seqn Id St Int Rpt
PLGNTSNQISHWD Q9NRT2 116 8 -
PLGNSSNQVSHWD P97438 116 8 -
PLGNTSNQISHWD O95069 131 8 -
PVGNSSNSSSHWD Q9JIS4 141 8 -

Motif 6 width=20
Element Seqn Id St Int Rpt
GIPLFGFLLAGVGDQLGTIF Q9NRT2 166 37 -
GIPLFGFLLAGVGDQLGTIF P97438 166 37 -
GIPLFGFLLAGVGDQLGTIF O95069 181 37 -
GIPLFGFLLAGIGDQLGTIF Q9JIS4 191 37 -

Motif 7 width=20
Element Seqn Id St Int Rpt
GKGIAKVEDTFIKWNVSQTK Q9NRT2 186 0 -
GKGIAKVEDTFIKWNVSQTK P97438 186 0 -
GKGIAKVEDTFIKWNVSQTK O95069 201 0 -
GKSIARVEKVFRKKQVSQTK Q9JIS4 211 0 -

Motif 8 width=12
Element Seqn Id St Int Rpt
RIISTIIFILFG Q9NRT2 207 1 -
RIISTIIFILFG P97438 207 1 -
RIISTIIFILFG O95069 222 1 -
RVISTILFILAG Q9JIS4 232 1 -

Motif 9 width=16
Element Seqn Id St Int Rpt
SDIEYLDFYKPVVWFW Q9NRT2 262 43 -
SDIEYLDFYKPVVWFW P97438 262 43 -
SDIEYLDFYKPVVWFW O95069 277 43 -
AGINYREWYKPLVWFW Q9JIS4 288 44 -

Motif 10 width=12
Element Seqn Id St Int Rpt
YFAAVLSMIGDW Q9NRT2 284 6 -
YFAAVLSMIGDW P97438 284 6 -
YFAAVLSMIGRL O95069 299 6 -
YFAAVLSMIGDW Q9JIS4 310 6 -

Motif 11 width=17
Element Seqn Id St Int Rpt
RVISKKTKEEVGEFRAH Q9NRT2 297 1 -
RVISKKTKEEVGEFRAH P97438 297 1 -
RVISKKTKEEVGEFRAH O95069 312 1 -
RVLSKKTKEEVGEIKAH Q9JIS4 323 1 -

Motif 12 width=15
Element Seqn Id St Int Rpt
SVEIYDKFQRATSIK Q9NRT2 333 19 -
SVEIYDKFQRATSVK P97438 333 19 -
SVEIYDKFQRATSIK O95069 348 19 -
SVEIHDKLQRAATIR Q9JIS4 359 19 -