WORKLIST ENTRIES (1):
GABAARRHO1 View alignment Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit signature
Type of fingerprint: COMPOUND with 3 elements
Links:
PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR; PR01670 GABAARRHO
PRINTS; PR01672 GABAARRHO2
MIM; 137161
Creation date 13-MAR-2002
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. RUDOLPH, U., CRESTANI, F. AND MOHLER, H.
GABA(A) receptor subtypes: dissecting their pharmacological functions.
TRENDS PHARMACOL.SCI. 22 188-194 (2001).
3. 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
(A) receptors: classification on the basis of subunit structure and receptor
function.
PHARMACOL.REV. 50 291-313 (1998).
4. BONNERT, T.P., MCKERNAN, R.M., FARRAR, S., LE BOURDELLES, B.,
HEAVENS, R.P., SMITH, D.W., HEWSON, L., RIGBY, M.R., SIRINATHSINGHJI, D.J.,
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).
5. ASHCROFT, F.M.
GABA(A) receptors.
IN ION CHANNELS AND DISEASE, ACADEMIC PRESS, 2000, PP.325-336.
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. ZHANG, D., PAN, Z.H., AWOBULUYI, M. AND LIPTON, S.A.
Structure and function of GABA(C) receptors: a comparison of native versus
recombinant receptors.
TRENDS PHARMACOL.SCI. 22(3) 121-132 (2001).
8. DREW, C.A., JOHNSTON, G.A. AND WEATHERBY, R.P.
Bicuculline-insensitive GABA receptors: studies on the binding of
(-)-baclofen to rat cerebellar membranes.
NEUROSCI.LETT. 52 317-321 (1984).
Gamma-aminobutyric acid type (GABA) is the major inhibitory neurotransmitter
in the vertebrate central nervous system (CNS). It modulates inhibitory tone
by interacting with two classes of receptor: ionotropic type A (GABAA) and
metabotropic type B (GABAB) receptors [1]. GABAA receptors are pentameric
membrane proteins that operate GABA-gated chloride channels [2] and belong
to the ligand-gated ion channel superfamily [1]. 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 [3,4].
Subunits are typically 50-60kDa in size and comprise a long N-terminal
extracellular domain; 4 putative transmembrane (TM) domains; and a large
cytoplasmic loop connecting the third and fourth TM domains [5]. 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].
The effects of GABA on GABAA receptors are modulated by a range of
therapeutically important drugs, including barbiturates, anaesthetics and
benzodiazepines (BZs), which include the widely prescribed drugs librium and
valium [1,5]. Furthermore, they are characterised by their sensitivity
towards a selective antagonist, bicuculline [7]. A second type of ionotropic
GABA receptor has been identified that is insensitive to bicuculline and
classical GABAA modulators but has an enhanced affinity for GABA. This
receptor was found to be composed principally of rho subunits and was termed
'GABAC' in recognition of its altered pharmacology [8]. Despite this
distinction, rho subunits are generally considered to be part of the GABAA
family of receptor proteins due to similarities in sequence and topology.
Whilst early studies supported the view that rho subunits assembled to form
a homopentamer, it has been shown that a mutant rho 1 protein is able to
coassemble with GABAA gamma 2 subunits as well as the glycine receptor alpha
subunit [7]. Rho subunit mRNA occurs prominently in both human and rat
retina [3], each subunit showing a characteristic pattern of spatial
expression. In rat retina, rho 1 mRNA has been detected only in bipolar
cells, whereas rho 2 transcripts have been detected in both bipolar and
ganglion cells. In retinal tissues, expression of rho 3 mRNA is exclusive to
ganglion cells [7]. Reverse transcriptase PCR (RT-PCR) and in situ
hybridisation have shown rho transcripts also to be present in other regions
of the brain, specifically those involved in visual signal processing, such
as the superior colliculus and visual cortex [7].
The gene encoding the rho 1 subunit is located on chromosome six, together
with the gene for rho 2. Labelling of rho subunit protein is only observed
in cells that express rho 1 mRNA. This finding suggests that either rho 1
has the highest level of expression or coassembly with rho 1 protein is
necessary for stable expression of other subunits [7].
GABAARRHO1 is a 3-element fingerprint that provides a signature for GABAA
receptor rho 1 subunits. 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 rho 1 subunits but distinguish them from the rest of the GABAA
receptor rho subunit family - motifs 1 and 2 lie at the N-terminus; and
motif 3 resides within the long cytoplasmic loop connecting TM domains 3 and
4 [7]. A single iteration on SPTR40_18f was required to reach convergence,
no further sequences being identified beyond the starting set.
SUMMARY INFORMATION
4 codes involving 3 elements
0 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
3| 4 4 4
2| 0 0 0
--+----------------
| 1 2 3
True positives..
GAR1_MOUSE GAR1_RAT GAR1_HUMAN O42157
PROTEIN TITLES
GAR1_MOUSE Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GA
GAR1_RAT Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GA
GAR1_HUMAN Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GA
O42157 GABAC RECEPTOR SUBUNIT RHO-1B - Morone americana (White perc
SCAN HISTORY
SPTR40_18f 1 300 NSINGLE
INITIAL MOTIF SETS
GABAARRHO11 Length of motif = 13 Motif number = 1
Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit motif I - 1
PCODE ST INT
GWVLAAESTAHWP GAR1_MOUSE 11 11
GWVLAAESTVHWP GAR1_RAT 11 11
GWVLATESRMHWP GAR1_HUMAN 11 11
CLVVIGECRKHKS O42157 13 13
GABAARRHO12 Length of motif = 12 Motif number = 2
Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit motif II - 1
PCODE ST INT
QRQRRGAHDDAH GAR1_MOUSE 38 14
QRQRRGAHDDAH GAR1_RAT 38 14
QRQRREVHEDAH GAR1_HUMAN 37 13
RKKRWSAPAETH O42157 26 0
GABAARRHO13 Length of motif = 13 Motif number = 3
Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit motif III - 1
PCODE ST INT
NGEKPDRMMVQLT GAR1_MOUSE 411 361
NGEKPDRMMVQLT GAR1_RAT 411 361
NGEKPDRMMVQLT GAR1_HUMAN 410 361
ASEKQERMVVHLS O42157 412 374
FINAL MOTIF SETS
GABAARRHO11 Length of motif = 13 Motif number = 1
Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit motif I - 1
PCODE ST INT
GWVLAAESTAHWP GAR1_MOUSE 11 11
GWVLAAESTVHWP GAR1_RAT 11 11
GWVLATESRMHWP GAR1_HUMAN 11 11
CLVVIGECRKHKS O42157 13 13
GABAARRHO12 Length of motif = 12 Motif number = 2
Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit motif II - 1
PCODE ST INT
QRQRRGAHDDAH GAR1_MOUSE 38 14
QRQRRGAHDDAH GAR1_RAT 38 14
QRQRREVHEDAH GAR1_HUMAN 37 13
RKKRWSAPAETH O42157 26 0
GABAARRHO13 Length of motif = 13 Motif number = 3
Gamma-aminobutyric-acid A (GABAA) receptor rho 1 subunit motif III - 1
PCODE ST INT
NGEKPDRMMVQLT GAR1_MOUSE 411 361
NGEKPDRMMVQLT GAR1_RAT 411 361
NGEKPDRMMVQLT GAR1_HUMAN 410 361
ASEKQERMVVHLS O42157 412 374
User query: Display/Full Code "GABAARRHO1"