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. LITTLETON, J.T. AND GANETZKY, B.
Ion channels and synaptic organisation: analysis of the Drosophila genome.
NEURON 26 35-43 (2000).
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, EAG 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) . 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 . However, unlike other families within this structural class,
EAG channels possess a cyclic nucleotide binding domain within their
putative intracellular C-termini.
The first EAG K+ channel was identified in Drosophila, following a screen
for mutations giving rise to behavioural abnormalities. Disruption of the
Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies
have revealed a conserved multi-gene family of EAG-like K+ channels, which
are present in Homo sapiens and many other species. Based on the varying
functional properties of the channels, the family has been divided into
3 subfamilies: EAG, ELK and ERG. Interestingly, C.elegans appears to lack
the ELK type .
EAGCHANLFMLY is a 10-element fingerprint that provides a signature for the
EAG/ELK/ERG K+ channel family. The fingerprint was derived from an initial
alignment of 10 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that
characterise the EAG/ELK/ERG channels but distinguish them from other
members of the K+ channel superfamily; motifs 1 and 2 span putative TM
domain 2; motifs 3 and 4 encompass TM domain 3; motif 5 spans TM domain 4;
motifs 6-9 encompass TM domain 5; and motif 10 encodes TM domain
6. Three iterations on SPTR39_14f were required to reach convergence, at
which point a true set comprising 32 sequences was identified.