| 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.97-123.
3. LITTLETON, J.T. AND GANETZKY, B.
Ion channels and synaptic organisation: analysis of the Drosophila genome.
NEURON 26 35-43 (2000).
4. MIYAKE, A., MOCHIZUKI, S., YOKOI, H., KOHDA, M. AND FURUICHI, K.
New ether-a-go-go K+ channel family members localised in human
telencephalon.
J.BIOL.CHEM. 274 25018-25025 (1999).
5. TRUDEAU, M.C., TITUS, S.A., BRANCHAW, J.L., GANETZKY, B.
AND ROBERTSON, G.A.
Functional analysis of a mouse brain Elk-type K+ channel.
J.NEUROSCIENCE 19(8) 2905-2918 (1999).
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| 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, 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) [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]. 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 [3].
Little is known about the properties of channels of the ELK subfamily.
However, when expressed in frog oocytes, they show properties between those
of the EAG and ERG subtypes. Included in this family are Bec1 and Bec2,
brain-specific genes found in the human telencephalon regions. It is thought
that they are involved in cellular excitability of restricted neurons in the
human central nervous system. Phylogenetic analysis reveals that these genes
constitute a subfamily with Elk within the Eag family [4]. Recently, a
further Elk subfamily member has been identified in mouse (Melk). On the
basis of sequence similarity, this indicates a distinct subclass within
this family [5].
ELKCHANNEL is a 6-element fingerprint that provides a signature for the ELK
potassium channel family. The fingerprint was derived from an initial
alignment of 4 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that
characterise the ELK channels but distinguish them from other members of
the K+ channel superfamily - motifs 1 and 2 reside within the N-terminal
domain; motif 3 spans the loop between putative TM domains 2 and 3; motif 4
encodes the loop between TM domains 4 and 5; motif 5 spans TM domain 6; and
motif 6 spans the C-terminal nucleotide binding domain. Three iterations on
SPTR39_14f were required to reach convergence, at which point a true set
comprising 9 sequences was identified.
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