| Literature References | 1. KOFUJI, P., WANG, J.B., MOSS, S.J., HUGANIR, R.L. AND BURT, D.R.
Generation of two forms of the gamma-aminobutyric acid A receptor gamma
2-subunit in mice by alternative splicing.
J.NEUROCHEM. 56 713-715 (1991).
2. WANG, J.B., KOFUJI, P., FERNANDO, J.C., MOSS, S.J., HUGANIR, R.L.
AND BURT, D.R.
The alpha 1, alpha 2, and alpha 3 subunits of GABAA receptors: comparison
in seizure-prone and -resistant mice and during development.
J.MOL.NEUROSCIENCE 3 177-184 (1992).
3. LEVITAN, E.S., SCHOFIELD, P.R., BURT, D.R., RHEE, L.M., WISDEN, W.,
KOHLER, M., FUJITA, N., RODRIGUEZ, H.F., STEPHENSON, A., DARLISON, M.G.,
BARNARD, E.A. AND SEEBURG, P.H.
Structural and functional basis for GABAA receptor heterogeneity.
NATURE 335 76-79 (1988).
4. KHRESTCHATISKY, M., MACLENNAN, A.J., TILLAKARATNE, N.J., CHIANG, M.Y.
AND TOBIN, A.J.
Sequence and regional distribution of the mRNA encoding the alpha 2
polypeptide of rat gamma-aminobutyric acid A receptors.
J.NEUROCHEM. 56 1717-1722 (1991).
5. THOMPSON, M., SHOTKOSKI, F. AND FFRENCH-CONSTANT, R.
Cloning and sequencing of the cyclodiene insecticide resistance gene from
the yellow fever mosquito Aedes aegypti. Conservation of the gene and
resistance associated mutation with Drosophila.
FEBS LETT. 325(3) 187-90 (1993).
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| Documentation | Gamma-aminobutyric acid (GABA) receptors are members of the neurotransmitter
ligand-gated ion channels: they mediate neuronal inhibition by opening
chloride channels on binding GABA [1,2]. There are 5 classes of receptor
subunit (alpha, beta, gamma, delta and rho), with variants in each class
[3]. Each subunit contains 4 proposed transmembrane (TM) domains, with a
large intracellular loop between the third and fourth domain. Active
receptors contain 5 subunits of varying classes and variants - the use
of highly similar receptor subtypes, which differ in functionality, is a
common feature of brain receptors [3].
The neurotransmitter action of the subtype A receptor (GABAA) is
potentiated by both benzodiazepines and barbiturates [3]. Alpha subunits
largely determine benzodiazepine binding properties [4], and gamma-2
subunits appear to be essential for benzodiazepine modulation of receptor
function [1]. In insects, cyclodiene (an insecticide) resistence is due to
insensitivity of the cyclodiene/picrotoxinin binding site on the GABAA
receptor-chloride ionophore complex [5].
GABAARECEPTR is a 4 element fingerprint that provides a signature for GABAA
receptors. The fingerprint was derived from an initial alignment of 15
sequences: the motifs were drawn from the 4 putative TM regions. Two
iterations on OWL24.0 were required to reach convergence, at which point a
true set comprising 60 sequences was identified: these include a number of
glycine receptors, which are inhibitory chloride ion channels known to
share a high degree of similarity with the GABA receptors.
An update on SPTR37_9f identified a true set of 113 sequences, and 10
partial matches.
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