WORKLIST ENTRIES (1):
GABAARGAMMA3 View alignment Gamma-aminobutyric-acid A receptor gamma 3 subunit signature
Type of fingerprint: COMPOUND with 4 elements
Links:
PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR; PR01620 GABAARGAMMA
PRINTS; PR01621 GABAARGAMMA1; PR01622 GABAARGAMMA2
MIM; 600233
Creation date 12-DEC-2001
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
(A) receptors: classification on the basis of subunit structure and receptor
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. MOHLER, H., CRESTANI, F. AND RUDOLPH, U.
GABA(A)-receptor subtypes: a new pharmacology.
CURR.OPIN.PHARMACOL. 1 22-25 (2001).
8. HERB, A., WISDEN, W., LUDDENS, H., PUIA, G., VICINI, S. AND SEEBERG, P.H.
The third gamma subunit of the gamma-aminobutyric acid type A receptor
family.
PROC.NATL.ACAD.SCI.U.S.A. 89 1433-1437 (1992).
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]. The large cytoplasmic loop displays the
most divergence in terms of primary structure amongst family members, with
the TM domains showing the highest level of sequence conservation [6].
Immunoprecipitation studies have shown that most GABAA receptors contain one
type of alpha and beta subunit, and a single gamma polypeptide in a ratio of
2:2:1 [1]. Whilst the critical residue involved in BZ binding is believed to
be located within the alpha subunit [7], the BZ binding site is considered
to be located at the interface between adjacent alpha and gamma subunits:
replacement of gamma subunits with delta and epsilon renders the receptor
insensitive to BZs due to disruption of the binding site [4]. Three
mammalian gamma subunits have been identified (gamma 1 to 3), each encoded
by a separate gene, plus an avian gamma 4 subunit.
The presence of a gamma 2 subunit, together with alpha 1, confers
'classical' BZ-binding activity to GABAA receptors; substitution for
gamma 1 or 3 leads to an altered binding profile for BZs [4]. The gamma 3
subunit confers a slightly reduced binding affinity for BZs when compared
to gamma 2-containing receptors [1], although the difference is not as
great as that observed for gamma 1-containing receptor subtypes.
GABAARGAMMA3 is a 4-element fingerprint that provides a signature for GABAA
gamma 3 subunits. The fingerprint was derived from an initial alignment of 3
sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise
gamma 3 subunits but distinguish them from the rest of the GABAA receptor
gamma subunit family - motif 1 resides in the extracellular N-terminal
domain; and motifs 2-4 lie in the cytoplasmic loop between TM domains 3 and
4 [8]. A single iteration on SPTR40_18f was required to reach convergence,
no further sequences being identified beyond the starting set.
SUMMARY INFORMATION
3 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
COMPOSITE FINGERPRINT INDEX
4| 3 3 3 3
3| 0 0 0 0
2| 0 0 0 0
--+---------------------
| 1 2 3 4
True positives..
GAC3_MOUSE GAC3_RAT GAC3_HUMAN
PROTEIN TITLES
GAC3_MOUSE Gamma-aminobutyric-acid receptor gamma-3 subunit precursor (
GAC3_RAT Gamma-aminobutyric-acid receptor gamma-3 subunit precursor (
GAC3_HUMAN Gamma-aminobutyric-acid receptor gamma-3 subunit precursor (
SCAN HISTORY
SPTR40_18f 1 300 NSINGLE
INITIAL MOTIF SETS
GABAARGAMMA31 Length of motif = 23 Motif number = 1
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif I - 1
PCODE ST INT
MAAKLLLLLCLFSGLHARSRRVE GAC3_MOUSE 1 1
MAAKLLLLLCLFSGLHARSRRVE GAC3_RAT 1 1
MAPKLLLLLCLFSGLHARSRKVE GAC3_HUMAN 1 1
GABAARGAMMA32 Length of motif = 19 Motif number = 2
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif II - 1
PCODE ST INT
CRKPTIRKKKTSLLHPDST GAC3_MOUSE 343 319
CRKPTIRKKKTSLLHPDST GAC3_RAT 343 319
CRKPTTTKKTTSLLHPDSS GAC3_HUMAN 343 319
GABAARGAMMA33 Length of motif = 18 Motif number = 3
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif III - 1
PCODE ST INT
WIPDRISLQAPSNYSLLD GAC3_MOUSE 363 1
WIPDRISLQAPSNYSLLD GAC3_RAT 363 1
WIPERISLQAPSNYSLLD GAC3_HUMAN 363 1
GABAARGAMMA34 Length of motif = 14 Motif number = 4
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif IV - 1
PCODE ST INT
MITLNNSMYWQEFE GAC3_MOUSE 388 7
MITLNNSMYWQEFE GAC3_RAT 388 7
MITLNNSVYWQEFE GAC3_HUMAN 388 7
FINAL MOTIF SETS
GABAARGAMMA31 Length of motif = 23 Motif number = 1
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif I - 1
PCODE ST INT
MAAKLLLLLCLFSGLHARSRRVE GAC3_MOUSE 1 1
MAAKLLLLLCLFSGLHARSRRVE GAC3_RAT 1 1
MAPKLLLLLCLFSGLHARSRKVE GAC3_HUMAN 1 1
GABAARGAMMA32 Length of motif = 19 Motif number = 2
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif II - 1
PCODE ST INT
CRKPTIRKKKTSLLHPDST GAC3_MOUSE 343 319
CRKPTIRKKKTSLLHPDST GAC3_RAT 343 319
CRKPTTTKKTTSLLHPDSS GAC3_HUMAN 343 319
GABAARGAMMA33 Length of motif = 18 Motif number = 3
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif III - 1
PCODE ST INT
WIPDRISLQAPSNYSLLD GAC3_MOUSE 363 1
WIPDRISLQAPSNYSLLD GAC3_RAT 363 1
WIPERISLQAPSNYSLLD GAC3_HUMAN 363 1
GABAARGAMMA34 Length of motif = 14 Motif number = 4
Gamma-aminobutyric-acid A receptor gamma 3 subunit motif IV - 1
PCODE ST INT
MITLNNSMYWQEFE GAC3_MOUSE 388 7
MITLNNSMYWQEFE GAC3_RAT 388 7
MITLNNSVYWQEFE GAC3_HUMAN 388 7
User query: Display/Full Code "GABAARGAMMA3"