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.97-123.
3. SANSOM, M.S.
Putting the parts together.
CURR.BIOL. 9(19) R738-R741 (1999).
4. CONLEY, E.C. AND BRAMMER, W.J.
IN THE ION CHANNEL FACTSBOOK, VOLUME IV, ACADEMIC PRESS, 1999, PP.617-646.
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 .
Structurally, Kv channels belong to the subfamily of K+ channels whose
subunits contain 6 transmembrane (TM) domains: these are the voltage-
gated K+ (Kv) channels, the KCNQ channels, the EAG-like K+ channels and
3 kinds of Ca2+-activated K+ channels (BK, IK and SK) . 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 [1-2].
The Kv family can be divided into 4 subfamilies on the basis of sequence
similarity and function: Shaker (Kv1), Shab (Kv2), Shaw (Kv3) and Shal
(Kv4). All consist of pore-forming alpha subunits that associate with
different types of beta subunit. To form a functional K+ channel pore,
4 alpha subunits and 4 beta subunits are required. The alpha subunits
have 6 well-conserved TM domains, a pore loop region and variable length
N- and C-termini. TM domains 5/6 and the loop region form the K+
channel pore through which the K+ ions pass .
The first Shal (Kv4) sequence was found in Drosophila. Several vertebrate
K+ channels with similar amino acid sequences were subsequently found and,
together with the Drosophila Shal channel, now constitute the Shal (Kv4)
family. These channels support outward K+-selective currents and are
inhibited by free fatty acids . The Shal family can be further divided
into 3 families, designated Kv4.1, Kv4.2 and Kv4.3.
SHALCHANNEL is a 9-element fingerprint that provides a signature for the
Shal voltage-gated K+ channel family. The fingerprint was derived from an
initial alignment of 8 sequences: the motifs were drawn from conserved
regions spanning the full alignment length: motifs 1-3 reside at the
N-terminus; motif 4 spans putative TM domain 1; motif 5 spans the loop
between TM domains 1 and 2; motif 6 spans TM domain 5; and motifs 7-9 reside
at the C-terminus. Two iterations on SPTR39_14f were required to reach
convergence, at which point a true set comprising 22 sequences was
identified. Several partial matches were also found, all of which are
members of the Shal family or are closely related potassium channels that
fail to make significant matches with one or more motifs.