WORKLIST ENTRIES (1):
KCNQ2CHANNEL View alignment KCNQ2 voltage-gated potassium channel signature
Type of fingerprint: COMPOUND with 4 elements
Links:
PRINTS; PR00169 KCHANNEL; PR01459 KCNQCHANNEL; PR01460 KCNQ1CHANNEL
PRINTS; PR01462 KCNQ3CHANNEL
Creation date 01-DEC-2000
1. MILLER, C.
An overview of the potassium channel family.
GENOME BIOL. 1(4) 1-5 (2000).
2. ASHCROFT, F.M.
Voltage-gated K+ channels.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.111-116.
3. SANGUINETTI, M. C.
Maximal function of minimal K+ channel subunits.
TRENDS PHARMACOL.SCI. 21 199-201 (2000).
4. WANG Q., CURRAN, M.E., SPLAWSKI, I., BURN, T.C., MILLHOLLAND, J.M.,
VANRAAY, T.J., SHEN, J., TIMOTHY, K.W., VINCENT, G.M., DE JAGER, T.,
SCHWARTZ, P.J., TOUBIN, J.A., MOSS, A.J., ATKINSON, D.L., LANDES, G.M.,
CONNORS, T.D. AND KEATING, M.T.
Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause
cardiac arrhythmias.
NAT.GENET. 12(1) 17-23 (1996).
5. BIERVERT, C., SCHROEDER, B.C., KUBISCH, C., BERKOVIC, S.F., PROPPING, P.,
JENTSCH, T.J. AND STEINLEIN O.K.
A potassium channel mutation in neonatal human epilepsy.
SCIENCE 279 403-406 (1998).
6. SCHROEDER, B.C., KUBISCH, C., STEIN, V. AND JENTSCH, T.J.
Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels
causes epilepsy.
NATURE 396 687-690 (1998).
Potassium ion (K+) channels are a structurally diverse group of proteins
that facilitate the flow of K+ ions across cell membranes. They are
ubiquitous, being present in virtually all cell types. Activation of K+
channels tends to hyperpolarise cells, reducing the membrane's electrical
resistance, dampening nervous activity. In eukaryotic cells, K+ channels
are involved in neural signalling and generation of the cardiac rhythm, and
act as effectors in signal transduction pathways involving G protein-
coupled receptors (GPCRs). In prokaryotic cells, they play a role in the
maintenance of ionic homeostasis [1].
Structurally, KCNQ channels belong to the subfamily of K+ channels whose
subunits contain 6 transmembrane (TM) domains: these are the voltage-gated
K+ channels, the KCNQ channels, the EAG-like K+ channels and 3 kinds of
Ca2+-activated K+ channel (BK, IK and SK) [2]. All K+ channels share a
characteristic sequence feature: a TMxTVGYG motif that resides between
the 2 C-terminal membrane-spanning helices, and forms the K+-selective
pore domain [1].
KCNQ channels differ from other voltage-gated 6 TM helix channels, chiefly
in that they possess no tetramerisation domain. Consequently, they rely on
interaction with accessory subunits, or form heterotetramers with other
members of the family [3]. Currently, 5 members of the KCNQ family are
known. These have been found to be widely distributed within the body,
having been shown to be expressed in the heart, brain, pancreas, lung,
placenta and ear. They were initially cloned as a result of a search for
proteins involved in cardiac arhythmia. Subsequently, mutations in other
KCNQ family members have been shown to be responsible for some forms of
hereditary deafness [4] and benign familial neonatal epilepsy [5].
The KCNQ2 channel subunit is thought to form active channels by hetero-
tetramerisation with KCNQ3, although some K+ channel activity does results
from the expression of KCNQ2 alone [6]. Channel function is modulated by
phosphorylation, since experiments have demonstrated that an increase in
intracellular cAMP concentration can enhance channel activity [2].
Frameshift mutations in both KCNQ2 and KCNQ3 are associated with benign
familial neonatal epilepsy [6], a disorder where an infant begins to suffer
convulsions, within the first three days of life. These symptoms usually
disappear after approximately three months, but affected individuals have a
higher than average chance of subsequently developing epilepsy (10-15%), in
later life [5].
KCNQ2CHANNEL is a 4-element fingerprint that provides a signature for the
KCNQ2 voltage-gated potassium channel. The fingerprint was derived from an
initial alignment of 16 sequences: the motifs were drawn from conserved
regions spanning the N-terminal third of the alignment, focusing on those
sections that characterise the KCNQ2 channel but distinguish it from other
members of the K+ channel superfamily - motifs 1 and 2 span the N-terminal
intracellular region; and motifs 3 and 4 span putative TM domains 1 and 2,
and the extracellular loop connecting them. Two iterations on SPTR39_14f
were required to reach convergence, at which point a true set comprising 17
sequences was identified. A single partial match was also found, CIQ4_HUMAN,
the closely related human KCNQ4 channel, which matches motifs 3 and 4.
SUMMARY INFORMATION
17 codes involving 4 elements
0 codes involving 3 elements
1 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
4| 17 17 17 17
3| 0 0 0 0
2| 0 0 1 1
--+---------------------
| 1 2 3 4
True positives..
O88943 Q9Z351 Q9Z350 Q9Z349
Q9Z348 Q9Z347 Q9Z345 Q9Z344
Q9Z343 Q9Z342 Q9QWN9 Q99454
O95845 O75580 O43796 O43526
Q9Z346
Subfamily: Codes involving 2 elements
Subfamily True positives..
CIQ4_HUMAN
PROTEIN TITLES
O88943 POTASSIUM CHANNEL - Rattus norvegicus (Rat).
Q9Z351 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z350 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z349 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z348 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z347 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z345 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z344 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z343 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9Z342 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q9QWN9 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
Q99454 NEUROBLASTOMA-SPECIFIC POTASSIUM CHANNEL PROTEIN - Homo sapi
O95845 POTASSIUM CHANNEL - Homo sapiens (Human).
O75580 NEURONAL DELAYED-RECTIFIER VOLTAGE-GATED POTASSIUM CHANNEL S
O43796 VOLTAGE GATED POTASSIUM CHANNEL - Homo sapiens (Human).
O43526 POTASSIUM CHANNEL - Homo sapiens (Human).
Q9Z346 ALTERNATIVE SPLICING:SEE ACCESSION BETWEEN AB000494 AND AB00
CIQ4_HUMAN VOLTAGE-GATED POTASSIUM CHANNEL PROTEIN KQT-LIKE 4 - Homo sa
SCAN HISTORY
SPTR39_14f 2 200 NSINGLE
INITIAL MOTIF SETS
KCNQ2CHANNEL1 Length of motif = 20 Motif number = 1
KCNQ2 voltage-gated potassium channel motif I - 1
PCODE ST INT
MVQKSRNGGVYPGPSGEKKL O75580 1 1
MVQKSRNGGVYPGTSGEKKL O88943 1 1
MVQKSRNGGVYPGPSGEKKL O43526 1 1
MVQKSRNGGVYPGPSGEKKL O95845 1 1
MVQKSRNGGVYPGPSGEKKL O43796 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z351 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z349 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z350 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z348 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z347 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z346 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z345 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z344 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z343 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z342 1 1
MVQKSRNGGVYPGPSGEKKL Q99454 1 1
KCNQ2CHANNEL2 Length of motif = 17 Motif number = 2
KCNQ2 voltage-gated potassium channel motif II - 1
PCODE ST INT
KVGFVGLDPGAPDSTRD O75580 21 0
KVGFVGLDPGAPDSTRD O88943 21 0
KVGFVGLDPGAPDSTRD O43526 21 0
KVGFVGLDPGAPDSTRD O95845 21 0
KVGFVGLDPGAPDSTRD O43796 21 0
KVGFVGLDPGAPDSTRD Q9Z351 21 0
KVGFVGLDPGAPDSTRD Q9Z349 21 0
KVGFVGLDPGAPDSTRD Q9Z350 21 0
KVGFVGLDPGAPDSTRD Q9Z348 21 0
KVGFVGLDPGAPDSTRD Q9Z347 21 0
KVGFVGLDPGAPDSTRD Q9Z346 21 0
KVGFVGLDPGAPDSTRD Q9Z345 21 0
KVGFVGLDPGAPDSTRD Q9Z344 21 0
KVGFVGLDPGAPDSTRD Q9Z343 21 0
KVGFVGLDPGAPDSTRD Q9Z342 21 0
KVGFVGLDPGAPDSTRD Q99454 21 0
KCNQ2CHANNEL3 Length of motif = 19 Motif number = 3
KCNQ2 voltage-gated potassium channel motif III - 1
PCODE ST INT
CLVLSVFSTIKEYEKSSEG O75580 106 68
CLVLSVFSTIKEYEKSSEG O88943 106 68
CLVLSVFSTIKEYEKSSEG O43526 106 68
CLVLSVFSTIKEYEKSSEG O95845 106 68
CLVLSVFSTIKEYEKSSEG O43796 106 68
CLVLSVFSTIKEYEKSSEG Q9Z351 106 68
CLVLSVFSTIKEYEKSSEG Q9Z349 106 68
CLVLSVFSTIKEYEKSSEG Q9Z350 106 68
CLVLSVFSTIKEYEKSSEG Q9Z348 106 68
CLVLSVFSTIKEYEKSSEG Q9Z347 106 68
CLVLSVFSTIKEYEKSSEG Q9Z346 106 68
CLVLSVFSTIKEYEKSSEG Q9Z345 106 68
CLVLSVFSTIKEYEKSSEG Q9Z344 106 68
CLVLSVFSTIKEYEKSSEG Q9Z343 106 68
CLVLSVFSTIKEYEKSSEG Q9Z342 106 68
CLVLSVFSTIKEYEKSSEG Q99454 106 68
KCNQ2CHANNEL4 Length of motif = 12 Motif number = 4
KCNQ2 voltage-gated potassium channel motif IV - 1
PCODE ST INT
ALYILEIVTIVV O75580 125 0
ALYILEIVTIVV O88943 125 0
ALYILEIVTIVV O43526 125 0
ALYILEIVTIVV O95845 125 0
ALYILEIVTIVV O43796 125 0
ALYILEIVTIVV Q9Z351 125 0
ALYILEIVTIVV Q9Z349 125 0
ALYILEIVTIVV Q9Z350 125 0
ALYILEIVTIVV Q9Z348 125 0
ALYILEIVTIVV Q9Z347 125 0
PLYILEIVTIVV Q9Z346 125 0
ALYILEIVTIVV Q9Z345 125 0
ALYILEIVTIVV Q9Z344 125 0
ALYILEIVTIVV Q9Z343 125 0
ALYILEIVTIVV Q9Z342 125 0
ALYILEIVTIVV Q99454 125 0
FINAL MOTIF SETS
KCNQ2CHANNEL1 Length of motif = 20 Motif number = 1
KCNQ2 voltage-gated potassium channel motif I - 2
PCODE ST INT
MVQKSRNGGVYPGTSGEKKL O88943 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z351 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z350 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z349 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z348 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z347 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z345 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z344 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z343 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z342 1 1
MVQKSRNGGVYPGTSGEKKL Q9QWN9 1 1
MVQKSRNGGVYPGPSGEKKL O43526 1 1
MVQKSRNGGVYPGPSGEKKL O43796 1 1
MVQKSRNGGVYPGPSGEKKL O75580 1 1
MVQKSRNGGVYPGPSGEKKL O95845 1 1
MVQKSRNGGVYPGPSGEKKL Q99454 1 1
MVQKSRNGGVYPGTSGEKKL Q9Z346 1 1
KCNQ2CHANNEL2 Length of motif = 17 Motif number = 2
KCNQ2 voltage-gated potassium channel motif II - 2
PCODE ST INT
KVGFVGLDPGAPDSTRD O88943 21 0
KVGFVGLDPGAPDSTRD Q9Z351 21 0
KVGFVGLDPGAPDSTRD Q9Z350 21 0
KVGFVGLDPGAPDSTRD Q9Z349 21 0
KVGFVGLDPGAPDSTRD Q9Z348 21 0
KVGFVGLDPGAPDSTRD Q9Z347 21 0
KVGFVGLDPGAPDSTRD Q9Z345 21 0
KVGFVGLDPGAPDSTRD Q9Z344 21 0
KVGFVGLDPGAPDSTRD Q9Z343 21 0
KVGFVGLDPGAPDSTRD Q9Z342 21 0
KVGFVGLDPGAPDSTRD Q9QWN9 21 0
KVGFVGLDPGAPDSTRD O43526 21 0
KVGFVGLDPGAPDSTRD O43796 21 0
KVGFVGLDPGAPDSTRD O75580 21 0
KVGFVGLDPGAPDSTRD O95845 21 0
KVGFVGLDPGAPDSTRD Q99454 21 0
KVGFVGLDPGAPDSTRD Q9Z346 21 0
KCNQ2CHANNEL3 Length of motif = 19 Motif number = 3
KCNQ2 voltage-gated potassium channel motif III - 2
PCODE ST INT
CLVLSVFSTIKEYEKSSEG O88943 106 68
CLVLSVFSTIKEYEKSSEG Q9Z351 106 68
CLVLSVFSTIKEYEKSSEG Q9Z350 106 68
CLVLSVFSTIKEYEKSSEG Q9Z349 106 68
CLVLSVFSTIKEYEKSSEG Q9Z348 106 68
CLVLSVFSTIKEYEKSSEG Q9Z347 106 68
CLVLSVFSTIKEYEKSSEG Q9Z345 106 68
CLVLSVFSTIKEYEKSSEG Q9Z344 106 68
CLVLSVFSTIKEYEKSSEG Q9Z343 106 68
CLVLSVFSTIKEYEKSSEG Q9Z342 106 68
CLVLSVFSTIKEYEKSSEG Q9QWN9 106 68
CLVLSVFSTIKEYEKSSEG O43526 106 68
CLVLSVFSTIKEYEKSSEG O43796 106 68
CLVLSVFSTIKEYEKSSEG O75580 106 68
CLVLSVFSTIKEYEKSSEG O95845 106 68
CLVLSVFSTIKEYEKSSEG Q99454 106 68
CLVLSVFSTIKEYEKSSEG Q9Z346 106 68
KCNQ2CHANNEL4 Length of motif = 12 Motif number = 4
KCNQ2 voltage-gated potassium channel motif IV - 2
PCODE ST INT
ALYILEIVTIVV O88943 125 0
ALYILEIVTIVV Q9Z351 125 0
ALYILEIVTIVV Q9Z350 125 0
ALYILEIVTIVV Q9Z349 125 0
ALYILEIVTIVV Q9Z348 125 0
ALYILEIVTIVV Q9Z347 125 0
ALYILEIVTIVV Q9Z345 125 0
ALYILEIVTIVV Q9Z344 125 0
ALYILEIVTIVV Q9Z343 125 0
ALYILEIVTIVV Q9Z342 125 0
ALYILEIVTIVV Q9QWN9 125 0
ALYILEIVTIVV O43526 125 0
ALYILEIVTIVV O43796 125 0
ALYILEIVTIVV O75580 125 0
ALYILEIVTIVV O95845 125 0
ALYILEIVTIVV Q99454 125 0
PLYILEIVTIVV Q9Z346 125 0
User query: Display/Full Code "KCNQ2CHANNEL"