| Literature References | 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).
|
| Documentation | 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 neotnatal epilepsy [5].
The KCNQ3 channel subunit is thought to form active channels by hetero-
tetramerisation with KCNQ2, although some K+ channel activity does result
from the expression of KCNQ3 alone [6]. Channel function is modulated by
phosphorylation; 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 in which infants suffer
convulsions within the first 3 days of life. These symptoms usually
disappear after about 3 months, but affected individuals have a higher
than average chance of subsequently developing epilepsy (10-15%) in later
life [5].
KCNQ3CHANNEL is a 9-element fingerprint that provides a signature for the
KCNQ3 voltage-gated potassium channel subtype. The fingerprint was derived
from an initial alignment of 3 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length, focusing
on those sections that characterise the KCNQ3 channel but distinguish it
from other members of the K+ channel superfamily - motif 1 lies within the
N-terminal intracellular region; motif 2 encodes the putative extracellular
loop between TM domains 1 and 2; motif 3 spans the C-terminal half of
putative TM domain 3; motif 4 encodes the putative cytoplasmic loop between
TM domains 4 and 5; and motifs 5-9 reside within the C-terminal intra-
cellular region. A single iteration on SPTR39_14f was required to reach
convergence, no further sequences being identified beyond the starting set.
|