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PR01160

Identifier
GABAARBETA  [View Relations]  [View Alignment]  
Accession
PR01160
No. of Motifs
4
Creation Date
21-MAR-1999
Title
Gamma-aminobutyric-acid A receptor beta subunit signature
Database References
PRINTS; PR00252 NRIONCHANNEL; PR00253 GABAARECEPTR
INTERPRO; IPR002289
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). 
 
6. HADINGHAM ,K.L., WINGROVE, P.B., WAFFORD, K.A., BAIN, C., KEMP, J.A.,
PALMER, K.J., WILSON, A.W., WILCOX, A.S., SIKELA, J.M. AND RAGAN, C.I.
Role of the beta subunit in determining the pharmacology of human gamma-
aminobutyric acid type A receptors.
MOL.PHARMACOL. 44 1211-1218 (1993).

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].
 
A cDNA encoding the human GABAA receptor beta 2 subunit has been cloned and
sequenced [6]. Expression of recombinant human GABAA receptors containing
different beta subunits (beta 1, beta 2 or beta 3) in both transfected
cells and Xenopus oocytes, has revealed the influence of the beta subunit on
the pharmacology of the receptor. For a number of benzodiazepine binding
site compounds, a barbiturate, and several neurosteroids, neither the
affinity nor the efficacy of the compounds is influenced by the type of
beta subunit present in the receptor molecule [6]. These observations
suggest that the beta subunit does not significantly influence the
benzodiazepine, barbiturate, or steroid site pharmacologies of human GABAA
receptor subtypes [6].
 
GABAARBETA is a 4-element fingerprint that provides a signature for GABAA
beta subunit precursors. The fingerprint was derived from an initial 
alignment of 13 sequences: the motifs were drawn from short conserved
regions spanning virtually the full alignment length, focusing on those
sections that characterise the beta subunits but distinguish them from 
the rest of the GABA receptor superfamily - motifs 1 and 2 lie within the
putative N-terminal extracellular domain; motif 3 encodes part of TM domain
3; and motif 4 lies at the C-terminus of the probable cytoplasmic domain.
Three iterations on SPTR37_9f were required to reach convergence, at which
point a true set comprising 19 sequences was identified. Several partial
matches were also found, which are largely GABA pi and rho subunits or 
glycine receptors that match 2 motifs.
Summary Information
  19 codes involving  4 elements
1 codes involving 3 elements
24 codes involving 2 elements
Composite Feature Index
419191919
30111
21152210
1234
True Positives
GAB1_BOVIN    GAB1_HUMAN    GAB1_MOUSE    GAB1_RAT      
GAB2_HUMAN GAB2_MOUSE GAB3_CHICK GAB3_DROME
GAB3_HUMAN GAB3_MOUSE GAB4_CHICK GAB_DROME
GAB_LYMST O17145 O18468 P92138
Q16323 Q16896 Q24561
True Positive Partials
Codes involving 3 elements
O18276
Codes involving 2 elements
DPYD_CAEEL GAAP_HUMAN GAAP_RAT GAR1_HUMAN
GAR1_MOUSE GAR1_RAT GRA1_HUMAN GRA1_MOUSE
GRA1_RAT GRA2_HUMAN GRA2_RAT GRA3_HUMAN
GRA3_RAT GRB_HUMAN GRB_MOUSE GRB_RAT
O23603 O33906 O72756 O75816
Q08861 Q18518 Q21005 YLJ2_CAEEL
Sequence Titles
GAB1_BOVIN  GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - BOS TAURUS (BOVINE). 
GAB1_HUMAN GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - HOMO SAPIENS (HUMAN).
GAB1_MOUSE GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - MUS MUSCULUS (MOUSE).
GAB1_RAT GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-1 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - RATTUS NORVEGICUS (RAT).
GAB2_HUMAN GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-2 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - HOMO SAPIENS (HUMAN).
GAB2_MOUSE GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-2 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - MUS MUSCULUS (MOUSE), AND RATTUS NORVEGICUS (RAT).
GAB3_CHICK GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-3 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - GALLUS GALLUS (CHICKEN).
GAB3_DROME GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-LIKE SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - DROSOPHILA MELANOGASTER (FRUIT FLY).
GAB3_HUMAN GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-3 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - HOMO SAPIENS (HUMAN).
GAB3_MOUSE GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-3 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - MUS MUSCULUS (MOUSE), AND RATTUS NORVEGICUS (RAT).
GAB4_CHICK GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA-4 SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - GALLUS GALLUS (CHICKEN).
GAB_DROME GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA SUBUNIT PRECURSOR (GABA(A) RECEPTOR) (CYCLODIENE RESISTANCE PROTEIN) - DROSOPHILA MELANOGASTER (FRUIT FLY).
GAB_LYMST GAMMA-AMINOBUTYRIC-ACID RECEPTOR BETA SUBUNIT PRECURSOR (GABA(A) RECEPTOR) - LYMNAEA STAGNALIS (GREAT POND SNAIL).
O17145 GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT - LUCILIA CUPRINA (GREENBOTTLE FLY) (AUSTRALIAN SHEEP BLOWFLY).
O18468 GABA-GATED CHLORIDE CHANNEL ISOFORM A2 - HELIOTHIS VIRESCENS (NOCTUID MOTH) (OWLET MOTH).
P92138 GABA-A RECEPTOR (GAMMA-AMINOBUTYRIC ACID RECEPTOR) - DROSOPHILA MELANOGASTER (FRUIT FLY).
Q16323 GABAA RECEPTOR BETA 2 SUBUNIT - HOMO SAPIENS (HUMAN).
Q16896 GABA RECEPTOR SUBUNIT - AEDES AEGYPTI (YELLOWFEVER MOSQUITO).
Q24561 GABA RECEPTOR - DROSOPHILA MELANOGASTER (FRUIT FLY).

O18276 ZC482.1 PROTEIN - CAENORHABDITIS ELEGANS.

DPYD_CAEEL PROBABLE DIHYDROPYRIMIDINE DEHYDROGENASE [NADP+] (EC 1.3.1.2) (DPD) (DIHYDROURACIL DEHYDROGENASE) (DIHYDROTHYMINE DEHYDROGENASE) - CAENORHABDITIS ELEGANS.
GAAP_HUMAN Gamma-aminobutyric-acid receptor pi subunit precursor (GABA(A) receptor) - Homo sapiens (Human).
GAAP_RAT Gamma-aminobutyric-acid receptor pi subunit precursor (GABA(A) receptor) - Rattus norvegicus (Rat).
GAR1_HUMAN Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GABA(A) receptor) - Homo sapiens (Human).
GAR1_MOUSE Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GABA(A) receptor) - Mus musculus (Mouse).
GAR1_RAT Gamma-aminobutyric-acid receptor rho-1 subunit precursor (GABA(A) receptor) - Rattus norvegicus (Rat).
GRA1_HUMAN Glycine receptor alpha-1 chain precursor (48 kDa) (Strychnine binding subunit) - Homo sapiens (Human).
GRA1_MOUSE Glycine receptor alpha-1 chain precursor (48 kDa) (Strychnine binding subunit) - Mus musculus (Mouse).
GRA1_RAT Glycine receptor alpha-1 chain precursor (48 kDa) (Strychnine binding subunit) - Rattus norvegicus (Rat).
GRA2_HUMAN Glycine receptor alpha-2 chain precursor - Homo sapiens (Human).
GRA2_RAT Glycine receptor alpha-2* chain precursor (Neonatal isoform) (Glycine receptor strychnine binding subunit) - Rattus norvegicus (Rat).
GRA3_HUMAN Glycine receptor alpha-3 chain precursor - Homo sapiens (Human).
GRA3_RAT Glycine receptor alpha-3 chain precursor - Rattus norvegicus (Rat).
GRB_HUMAN Glycine receptor beta chain precursor - Homo sapiens (Human).
GRB_MOUSE Glycine receptor beta chain precursor - Mus musculus (Mouse).
GRB_RAT Glycine receptor beta chain precursor (58 kDa) - Rattus norvegicus (Rat).
O23603 HYPOTHETICAL 130.3 KD PROTEIN - ARABIDOPSIS THALIANA (MOUSE-EAR CRESS).
O33906 HYPOTHETICAL 216.9 KD PROTEIN - SHEWANELLA SP. SCRC-2738.
O72756 B19R PROTEIN - COWPOX VIRUS (CPV).
O75816 GLYCINE RECEPTOR ALPHA 3 SUBUNIT - HOMO SAPIENS (HUMAN).
Q08861 GAMMA-AMINOBUTYRIC ACID-GATED CHLORIDE-ION CHANNEL/RECEPTOR, ZETA SUBUNIT PRECURSOR - LYMNAEA STAGNALIS (GREAT POND SNAIL).
Q18518 C39B10.2 PROTEIN - CAENORHABDITIS ELEGANS.
Q21005 F58G6.4 PROTEIN - CAENORHABDITIS ELEGANS.
YLJ2_CAEEL HYPOTHETICAL 256.3 KD PROTEIN C50C3.2 IN CHROMOSOME III - CAENORHABDITIS ELEGANS.
Scan History
SPTR37_9f  2  414  NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
RLSYSGIPLNLTLDN GAB1_RAT 96 96 -
RLSYSGIPLNLTLDN GAB1_MOUSE 96 96 -
RLSYSGIPLNLTLDN GAB1_HUMAN 96 96 -
RLSYSGIPLNLTLDN GAB1_BOVIN 96 96 -
RLAYSGIPLNLTLDN GAB3_HUMAN 96 96 -
RLAYSGIPLNLTLDN GAB3_MOUSE 96 96 -
RLAYAGIPLNLTLDN GAB3_CHICK 96 96 -
RLSYNVIPLNLTLDN GAB2_MOUSE 95 95 -
RLSYNVIPLNLTLDN GAB2_HUMAN 95 95 -
RLAYNDLPLNLTLDN GAB4_CHICK 95 95 -
RLAYRKRPGVETLSV GAB_DROME 118 118 -
RLAFNIFGQYFDDEN GAB3_DROME 99 99 -
RLQFIFNESLDLGEN GAB_LYMST 92 92 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VTGVNKIELPQFSI GAB1_RAT 200 89 -
VTGVNKIELPQFSI GAB1_MOUSE 200 89 -
VTGVNKIELPQFSI GAB1_HUMAN 200 89 -
VTGVNKIELPQFSI GAB1_BOVIN 200 89 -
VTGVERIELPQFSI GAB3_HUMAN 200 89 -
VTGVERIELPQFSI GAB3_MOUSE 200 89 -
VTGVERIELPQFSI GAB3_CHICK 200 89 -
VTGVTKIELPQFSI GAB2_MOUSE 199 89 -
VTGVTKIELPQFSI GAB2_HUMAN 199 89 -
VTGMEVLELPQFTI GAB4_CHICK 199 89 -
VGMSSEVELPQFRV GAB_DROME 224 91 -
VRGVEDAELPQFTI GAB3_DROME 213 99 -
VTGVEDVSLPQFSI GAB_LYMST 206 99 -

Motif 3 width=13
Element Seqn Id St Int Rpt
IPYVKAIDIYLMG GAB1_RAT 300 86 -
IPYVKAIDIYLMG GAB1_MOUSE 300 86 -
IPYVKAIDIYLMG GAB1_HUMAN 300 86 -
IPYVKAIDIYLMG GAB1_BOVIN 300 86 -
IPYVKAIDMYLMG GAB3_HUMAN 300 86 -
IPYVKAIDMYLMG GAB3_MOUSE 300 86 -
IPYVKAIDMYLMG GAB3_CHICK 300 86 -
IPYVKAIDMYLMG GAB2_MOUSE 299 86 -
IPYVKAIDMYLMG GAB2_HUMAN 299 86 -
IPYVKAIDVYLMG GAB4_CHICK 299 86 -
ISYVKSIDVYLGT GAB_DROME 324 86 -
ISYVKAIDIYLVM GAB3_DROME 313 86 -
ISYVKAIDIYLVM GAB_LYMST 306 86 -

Motif 4 width=15
Element Seqn Id St Int Rpt
IPDLTDVNSIDKWSR GAB1_RAT 440 127 -
IPDLTDVNSIDKWSR GAB1_MOUSE 440 127 -
IPDLTDVNSIDKWSR GAB1_HUMAN 440 127 -
IPDLTDVNSIDKWSR GAB1_BOVIN 440 127 -
IPDLTDVNAIDRWSR GAB3_HUMAN 439 126 -
IPDLTDVNAIDRWSR GAB3_MOUSE 439 126 -
IPDLTDVNAIDRWSR GAB3_CHICK 442 129 -
IPDLTDVNAIDRWSR GAB2_MOUSE 440 128 -
IPDLTDVNAIDRWSR GAB2_HUMAN 440 128 -
IPDLTDVSTIDKWSR GAB4_CHICK 454 142 -
KLLGITPSDIDKYSR GAB_DROME 557 220 -
IPKIKDVNIIDKYSR GAB3_DROME 461 135 -
IPRVQDVNTIDKYAR GAB_LYMST 464 145 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
RLSYSGIPLNLTLDN GAB1_RAT 96 96 -
RLSYSGIPLNLTLDN GAB1_MOUSE 96 96 -
RLSYSGIPLNLTLDN GAB1_HUMAN 96 96 -
RLSYSGIPLNLTLDN GAB1_BOVIN 96 96 -
RLAYSGIPLNLTLDN GAB3_HUMAN 96 96 -
RLAYSGIPLNLTLDN GAB3_MOUSE 96 96 -
RLAYAGIPLNLTLDN GAB3_CHICK 96 96 -
RLSYNVIPLNLTLDN Q16323 95 95 -
RLSYNVIPLNLTLDN GAB2_MOUSE 95 95 -
RLSYNVIPLNLTLDN GAB2_HUMAN 95 95 -
RLAYNDLPLNLTLDN GAB4_CHICK 95 95 -
RLAYRKRPGVETLSV GAB_DROME 118 118 -
RLAYRKRPGVETLSV P92138 113 113 -
RLAYRKRPGVETLSV Q16896 113 113 -
RLAYGKRPGVETLSV Q24561 118 118 -
RLAYRKRPGVETLSV O17145 116 116 -
RLAYKKRTGVETLSV O18468 102 102 -
RLAFNIFGQYFDDEN GAB3_DROME 99 99 -
RLQFIFNESLDLGEN GAB_LYMST 92 92 -

Motif 2 width=14
Element Seqn Id St Int Rpt
VTGVNKIELPQFSI GAB1_RAT 200 89 -
VTGVNKIELPQFSI GAB1_MOUSE 200 89 -
VTGVNKIELPQFSI GAB1_HUMAN 200 89 -
VTGVNKIELPQFSI GAB1_BOVIN 200 89 -
VTGVERIELPQFSI GAB3_HUMAN 200 89 -
VTGVERIELPQFSI GAB3_MOUSE 200 89 -
VTGVERIELPQFSI GAB3_CHICK 200 89 -
VTGVTKIELPQFSI Q16323 199 89 -
VTGVTKIELPQFSI GAB2_MOUSE 199 89 -
VTGVTKIELPQFSI GAB2_HUMAN 199 89 -
VTGMEVLELPQFTI GAB4_CHICK 199 89 -
VGMSSEVELPQFRV GAB_DROME 224 91 -
VGMSSEVELPQFRV P92138 219 91 -
VGMSSEVELPQFRV Q16896 219 91 -
VGVSSEVSLPQFKV Q24561 224 91 -
VGVSNEVSLPQFKV O17145 222 91 -
VGVSSEVSLPQFKV O18468 208 91 -
VRGVEDAELPQFTI GAB3_DROME 213 99 -
VTGVEDVSLPQFSI GAB_LYMST 206 99 -

Motif 3 width=13
Element Seqn Id St Int Rpt
IPYVKAIDIYLMG GAB1_RAT 300 86 -
IPYVKAIDIYLMG GAB1_MOUSE 300 86 -
IPYVKAIDIYLMG GAB1_HUMAN 300 86 -
IPYVKAIDIYLMG GAB1_BOVIN 300 86 -
IPYVKAIDMYLMG GAB3_HUMAN 300 86 -
IPYVKAIDMYLMG GAB3_MOUSE 300 86 -
IPYVKAIDMYLMG GAB3_CHICK 300 86 -
IPYVKAIDMYLMG Q16323 299 86 -
IPYVKAIDMYLMG GAB2_MOUSE 299 86 -
IPYVKAIDMYLMG GAB2_HUMAN 299 86 -
IPYVKAIDVYLMG GAB4_CHICK 299 86 -
ISYVKSIDVYLGT GAB_DROME 324 86 -
ISYVKSIDVYLGT P92138 319 86 -
ISYVKSIDVYLGT Q16896 319 86 -
ISYVKSIDVYLGT Q24561 324 86 -
ISYVKSIDVYLGA O17145 322 86 -
ISYVKSIDVYLGT O18468 308 86 -
ISYVKAIDIYLVM GAB3_DROME 313 86 -
ISYVKAIDIYLVM GAB_LYMST 306 86 -

Motif 4 width=15
Element Seqn Id St Int Rpt
IPDLTDVNSIDKWSR GAB1_RAT 440 127 -
IPDLTDVNSIDKWSR GAB1_MOUSE 440 127 -
IPDLTDVNSIDKWSR GAB1_HUMAN 440 127 -
IPDLTDVNSIDKWSR GAB1_BOVIN 440 127 -
IPDLTDVNAIDRWSR GAB3_HUMAN 439 126 -
IPDLTDVNAIDRWSR GAB3_MOUSE 439 126 -
IPDLTDVNAIDRWSR GAB3_CHICK 442 129 -
IPDLTDVNAIDRWSR Q16323 478 166 -
IPDLTDVNAIDRWSR GAB2_MOUSE 440 128 -
IPDLTDVNAIDRWSR GAB2_HUMAN 440 128 -
IPDLTDVSTIDKWSR GAB4_CHICK 454 142 -
KLLGITPSDIDKYSR GAB_DROME 557 220 -
KLLGITPSDIDKYSR P92138 552 220 -
KLLGITPSDIDKYSR Q16896 483 151 -
KLLGITPSDIDKYSR Q24561 557 220 -
KLLGITPSDIDKYSR O17145 501 166 -
KLLGTTPSDIDKYSR O18468 446 125 -
IPKIKDVNIIDKYSR GAB3_DROME 461 135 -
IPRVQDVNTIDKYAR GAB_LYMST 464 145 -