SPRINT Home UMBER Home Contents Standard Search Advanced Search Relation Search

==SPRINT==> PRINTS View



  selected as


PR01725

Identifier
GABAARTHETA  [View Relations]  [View Alignment]  
Accession
PR01725
No. of Motifs
5
Creation Date
07-JUN-2002
Title
Gamma-aminobutyric-acid A receptor theta subunit signature
Database References
PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR
MIM; 300349
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).    

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].
 
Identification and characterisation of the theta subunit was first reported
in 1999 [5]. Cloning of the full-length cDNA was performed using a human
whole-brain library, yielding a deduced open reading frame of 627 amino
acids. This polypeptide was found to be most similar to the beta 1 subunit
with regard to sequence identity, and was able to co-assemble with alpha 2,
beta 1 and gamma 1 subunits, yielding heteromeric assemblies with a 4-fold
increase in sensitivity towards GABA. Furthermore, theta mRNA was found 
to have a unique spatial distribution, with significant expression within
monoaminergic neurons of both human and monkey brain.      
 
GABAARTHETA is a 5-element fingerprint that provides a signature for GABAA
receptor theta 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 theta subunits but distinguish them from the rest of the GABAA
receptor subunit family - motif 1 lies at the N-terminus; and motifs 2-5
reside within the large cytoplasmic loop between TM domains 3 and 4. A
single iteration on SPTR40_20f was required to reach convergence, no further
sequences being identified beyond the starting set.  
Summary Information
3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
300000
200000
12345
True Positives
GAAT_HUMAN    GAAT_MOUSE    Q91ZM7        
Sequence Titles
GAAT_HUMAN  Gamma-aminobutyric-acid receptor theta subunit precursor (GABA(A) receptor) - Homo sapiens (Human). 
GAAT_MOUSE Gamma-aminobutyric-acid receptor theta subunit precursor (GABA(A) receptor) - Mus musculus (Mouse).
Q91ZM7 GABA THETA SUBUNIT - Rattus norvegicus (Rat).
Scan History
SPTR40_20f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
FHFELSSSMPEVILDLFNCKNCANE Q91ZM7 27 27 -
FHFELSSSTPEVILDLFNCKNCANE GAAT_MOUSE 32 32 -
FHFEFSSAVPEVVLNLFNCKNCANE GAAT_HUMAN 32 32 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LPDSPMQAHLASQ Q91ZM7 397 345 -
LPDSPMQAHLASQ GAAT_MOUSE 402 345 -
LPITPAQAPLASP GAAT_HUMAN 399 342 -

Motif 3 width=14
Element Seqn Id St Int Rpt
GFLTNDSILPIKIR Q91ZM7 468 58 -
GFLTNDSIIPIKIH GAAT_MOUSE 473 58 -
GFQADDSIFPTEIR GAAT_HUMAN 470 58 -

Motif 4 width=22
Element Seqn Id St Int Rpt
KGDADSIWSLTDEELMACDQEK Q91ZM7 552 70 -
KGDADSIWSLTDEELMACDQEK GAAT_MOUSE 557 70 -
KCDTNSTWGLNDDELMAHGQEK GAAT_HUMAN 551 67 -

Motif 5 width=25
Element Seqn Id St Int Rpt
ESEESCSPSPGCSFNEGFSFQLFNP Q91ZM7 580 6 -
ESEENCSPSPGCSFNEGFSFQLFKP GAAT_MOUSE 583 4 -
ESEDSCPPSPGCSFTEGFSFDLFNP GAAT_HUMAN 577 4 -
Final Motifs
Motif 1  width=25
Element Seqn Id St Int Rpt
FHFELSSSMPEVILDLFNCKNCANE Q91ZM7 27 27 -
FHFELSSSTPEVILDLFNCKNCANE GAAT_MOUSE 32 32 -
FHFEFSSAVPEVVLNLFNCKNCANE GAAT_HUMAN 32 32 -

Motif 2 width=13
Element Seqn Id St Int Rpt
LPDSPMQAHLASQ Q91ZM7 397 345 -
LPDSPMQAHLASQ GAAT_MOUSE 402 345 -
LPITPAQAPLASP GAAT_HUMAN 399 342 -

Motif 3 width=14
Element Seqn Id St Int Rpt
GFLTNDSILPIKIR Q91ZM7 468 58 -
GFLTNDSIIPIKIH GAAT_MOUSE 473 58 -
GFQADDSIFPTEIR GAAT_HUMAN 470 58 -

Motif 4 width=22
Element Seqn Id St Int Rpt
KGDADSIWSLTDEELMACDQEK Q91ZM7 552 70 -
KGDADSIWSLTDEELMACDQEK GAAT_MOUSE 557 70 -
KCDTNSTWGLNDDELMAHGQEK GAAT_HUMAN 551 67 -

Motif 5 width=25
Element Seqn Id St Int Rpt
ESEESCSPSPGCSFNEGFSFQLFNP Q91ZM7 580 6 -
ESEENCSPSPGCSFNEGFSFQLFKP GAAT_MOUSE 583 4 -
ESEDSCPPSPGCSFTEGFSFDLFNP GAAT_HUMAN 577 4 -