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PR01722

Identifier
GABAARDELTA  [View Relations]  [View Alignment]  
Accession
PR01722
No. of Motifs
3
Creation Date
07-JUN-2002
Title
Gamma-aminobutyric-acid A receptor delta subunit signature
Database References
PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR
Literature References
1. WHITING, P.J., MCKERNAN, R.M. AND WAFFORD, K.A.
Structure and pharmacology of vertebrate GABA(A) receptor subtypes.
INT.REV.NEUROBIOL. 38 95-138 (1995).
 
2. ASHCROFT, F.M.
GABA(A) receptors.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.325-336.
 
3. RUDOLPH, U., CRESTANI, F. AND MOHLER, H.
GABA(A) receptor subtypes: dissecting their pharmacological functions.
TRENDS PHARMACOL.SCI. 22 188-194 (2001).
 
4. BARNARD, E.A., SKOLNICK, P., OLSEN, R.W., MOHLER, H., SIEGHART, W.,
BIGGIO, G., BRAESTRUP, C., BATESON, A.N. AND LANGER, S.Z.
International Union of Pharmacology: XV. Subtypes of gamma-aminobutyric acid
function.
PHARMACOL.REV. 50 291-313 (1998).
 
5. BONNERT, T.P., MCKERNAN, R.M., FARRAR, S., LE BOURDELLES, B.,
HEAVENS, R.P., SMITH, D.W., HEWSON, L., RIGBY, M.R., SIRINATHSINGHJI,
BROWN, N., WAFFORD, K.A. AND WHITING, P.J.
Theta, a novel gamma-aminobutyric acid type A receptor subunit.
PROC.NATL.ACAD.SCI.U.S.A. 96 9891-9896 (1999).
 
6. PRITCHETT, D.B., SONTHEIMER, H., SHIVERS, B.D., YMER, S., KETTENMANN, H.,
SCHOFIELD, P.R. AND SEEBERG, P.H.
Importance of a novel GABA(A) receptor subunit for benzodiazepine
pharmacology.
NATURE 338 582-585 (1989). 
 
7. SHIVERS, B.D., KILLISCH, I., SPRENGEL, R., SONTHEIMER, H., KOHLER, M., 
SCHOFIELD, P.R. AND SEEBERG, P.H.
Two novel GABAA receptor subunits exist in distinct neuronal subpopulations.
NEURON 3 327-337 (1989).

Documentation
Gamma-aminobutyric acid type A (GABAA) receptors are members of the neuro-
transmitter ligand-gated ion channels: they mediate neuronal inhibition on
binding GABA. The effects of GABA on GABAA receptors are modulated by a range
of therapeutically important drugs, including barbiturates, anaesthetics and
benzodiazepines (BZs) [1,2]. The BZs are a diverse range of compounds,
including widely prescribed drugs, such as librium and valium, and their
interaction with GABAA receptors provides the most potent pharmacological
means of distinguishing different GABAA receptor subtypes [1].
 
GABAA receptors are pentameric membrane proteins that operate GABA-gated
chloride channels [3]. Eight types of receptor subunit have been cloned,
with multiple subtypes within some classes: alpha 1-6, beta 1-4, gamma 1-4,
delta, epsilon, pi, rho 1-3 and theta [4,5]. Subunits are typically 50-60kDa
in size and comprise a long N-terminal extracellular domain, containing
a putative signal peptide and a disulphide-bonded beta structural loop; 4
putative transmembrane (TM) domains; and a large cytoplasmic loop connecting
the third and fourth TM domains [2]. Amongst family members, the large
cytoplasmic loop displays the most divergence in terms of primary structure,
the TM domains showing the highest level of sequence conservation [6].
 
Evidence suggests that the structure of GABAA receptors is analagous to that
of the nicotinic acetylcholine receptor, namely a pentameric protein with
the ion channel located in the centre of a rosette formed between five 
homologous subunits [4]. The majority of receptors contain one type of alpha
and beta subunit, and a single gamma polypeptide in a ratio of 2:2:1 [1].
 
Isolation of delta cDNA from a rat brain library was first reported in 1989
[7]. Orthologues were later identified in mouse and humans [1]. Delta mRNA
was found to be present in regions of the brain that were low in gamma 2, 
and insensitivity towards "classical" BZs was observed in receptors
containing the delta subunit. Furthermore, delta subunits are thought to 
preferentially pair with the alpha 6 polypeptides over other subtypes, and 
are often found in place of gamma subunits [4].   
 
GABAARDELTA is a 3-element fingerprint that provides a signature for GABAA
receptor delta subunits. The fingerprint was derived from an initial
alignment of 3 sequences: the motifs were drawn from conserved regions
spanning the full alignment length, focusing on those sections that
characterise delta subunits but distinguish them from the rest of the GABAA
receptor subunit family - motif 1 lies at the N-terminus; and motifs 2 and 3
reside within the large cytoplasmic loop between TM domains 3 and 4. Two 
iterations on SPTR40_20f were required to reach convergence, at which point
a true set comprising 4 sequences was identified.
Summary Information
4 codes involving  3 elements
0 codes involving 2 elements
Composite Feature Index
3444
2000
123
True Positives
GAD_HUMAN     GAD_MOUSE     GAD_RAT       Q8VBV6        
Sequence Titles
GAD_HUMAN   Gamma-aminobutyric-acid receptor delta subunit precursor (GABA(A) receptor) - Homo sapiens (Human). 
GAD_MOUSE Gamma-aminobutyric-acid receptor delta subunit precursor (GABA(A) receptor) - Mus musculus (Mouse).
GAD_RAT Gamma-aminobutyric-acid receptor delta subunit precursor (GABA(A) receptor) - Rattus norvegicus (Rat).
Q8VBV6 GAMMA-AMINOBUTYRIC ACID RECEPTOR, SUBUNIT DELTA - Mus musculus (Mouse).
Scan History
SPTR40_20f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
CTQPHHGARAMNDIGDYVGSNLE GAD_MOUSE 15 15 -
CTQPHHGARAMNDIGDYVGSNLE GAD_RAT 15 15 -
CAQQLRGTRAMNDIGDYVGSNLE GAD_HUMAN 15 15 -

Motif 2 width=19
Element Seqn Id St Int Rpt
HFNADYRKKRKAKVKVTKP GAD_MOUSE 332 294 -
HFNADYRKKRKAKVKVTKP GAD_RAT 332 294 -
HFNADYRKKQKAKVKVSRP GAD_HUMAN 332 294 -

Motif 3 width=22
Element Seqn Id St Int Rpt
SAAGVSQELAISRRQGRVPGNL GAD_MOUSE 366 15 -
SAAGVSQELAISRRQGRVPGNL GAD_RAT 366 15 -
SAAGVTQELAISRRQRRVPGNL GAD_HUMAN 366 15 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
CTQPHHGARAMNDIGDYVGSNLE GAD_MOUSE 15 15 -
CTQPHHGARAMNDIGDYVGSNLE GAD_RAT 15 15 -
CTQPHHGARAMNDIGDYVGSNLE Q8VBV6 15 15 -
CAQQLRGTRAMNDIGDYVGSNLE GAD_HUMAN 15 15 -

Motif 2 width=19
Element Seqn Id St Int Rpt
HFNADYRKKRKAKVKVTKP GAD_MOUSE 332 294 -
HFNADYRKKRKAKVKVTKP GAD_RAT 332 294 -
HFNADYRKKRKAKVKVTKP Q8VBV6 332 294 -
HFNADYRKKQKAKVKVSRP GAD_HUMAN 332 294 -

Motif 3 width=22
Element Seqn Id St Int Rpt
SAAGVSQELAISRRQGRVPGNL GAD_MOUSE 366 15 -
SAAGVSQELAISRRQGRVPGNL GAD_RAT 366 15 -
SAAGVSQELAISRRQDRVPGNL Q8VBV6 366 15 -
SAAGVTQELAISRRQRRVPGNL GAD_HUMAN 366 15 -