GBRB_DROME
ID GBRB_DROME Reviewed; 606 AA.
AC P25123; P92138; Q24561; Q26302; Q7JPX8; Q8IQB5; Q8IQB6; Q961R4; Q9TX51;
AC Q9VSV0;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 4.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit beta;
DE AltName: Full=GABA(A) receptor subunit beta;
DE AltName: Full=Protein cyclodiene resistance;
DE Flags: Precursor;
GN Name=Rdl; ORFNames=CG10537;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), AND RNA EDITING OF POSITION 283.
RC TISSUE=Embryo;
RX PubMed=1651498; DOI=10.1073/pnas.88.16.7209;
RA ffrench-Constant R.H., Mortlock D.P., Shaffer C.D., Macintyre R.J.,
RA Roush R.T.;
RT "Molecular cloning and transformation of cyclodiene resistance in
RT Drosophila: an invertebrate gamma-aminobutyric acid subtype A receptor
RT locus.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:7209-7213(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, ACTIVITY REGULATION, AND
RP RNA EDITING OF POSITIONS 122; 283 AND 360.
RC TISSUE=Head;
RX PubMed=8016117; DOI=10.1073/pnas.91.13.6069;
RA Chen R., Belelli D., Reyes A., Lambert J.J., Peters J.A., Lan N.C.;
RT "Cloning and functional expression of a Drosophila gamma-aminobutyric acid
RT receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6069-6073(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D), AND RNA EDITING OF
RP POSITION 283.
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 70-113 (ISOFORMS A/D).
RX PubMed=7684073; DOI=10.1111/j.1471-4159.1993.tb03523.x;
RA ffrench-Constant R.H., Rocheleau T.A.;
RT "Drosophila gamma-aminobutyric acid receptor gene Rdl shows extensive
RT alternative splicing.";
RL J. Neurochem. 60:2323-2326(1993).
RN [7]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ALA-301.
RX PubMed=8389005; DOI=10.1038/363449a0;
RA Ffrench-Constant R.H., Rocheleau T.A., Steichen J.C., Chalmers A.E.;
RT "A point mutation in a Drosophila GABA receptor confers insecticide
RT resistance.";
RL Nature 363:449-451(1993).
RN [8]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ALA-301.
RX PubMed=7527461; DOI=10.1113/jphysiol.1994.sp020278;
RA Zhang H.G., ffrench-Constant R.H., Jackson M.B.;
RT "A unique amino acid of the Drosophila GABA receptor with influence on drug
RT sensitivity by two mechanisms.";
RL J. Physiol. (Lond.) 479:65-75(1994).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=8882620; DOI=10.1111/j.1476-5381.1996.tb16720.x;
RA Hosie A.M., Sattelle D.B.;
RT "Allosteric modulation of an expressed homo-oligomeric GABA-gated chloride
RT channel of Drosophila melanogaster.";
RL Br. J. Pharmacol. 117:1229-1237(1996).
RN [10]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=12805302; DOI=10.1523/jneurosci.23-11-04625.2003;
RA Lee D., Su H., O'Dowd D.K.;
RT "GABA receptors containing Rdl subunits mediate fast inhibitory synaptic
RT transmission in Drosophila neurons.";
RL J. Neurosci. 23:4625-4634(2003).
RN [11]
RP RNA EDITING.
RX PubMed=12907802; DOI=10.1126/science.1086763;
RA Hoopengardner B., Bhalla T., Staber C., Reenan R.;
RT "Nervous system targets of RNA editing identified by comparative
RT genomics.";
RL Science 301:832-836(2003).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=18093529; DOI=10.1016/j.neuron.2007.10.036;
RA Liu X., Krause W.C., Davis R.L.;
RT "GABAA receptor RDL inhibits Drosophila olfactory associative learning.";
RL Neuron 56:1090-1102(2007).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF ALA-301 AND MET-360.
RX PubMed=18223647; DOI=10.1038/nn2046;
RA Agosto J., Choi J.C., Parisky K.M., Stilwell G., Rosbash M., Griffith L.C.;
RT "Modulation of GABAA receptor desensitization uncouples sleep onset and
RT maintenance in Drosophila.";
RL Nat. Neurosci. 11:354-359(2008).
RN [14]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19038223; DOI=10.1016/j.neuron.2008.10.042;
RA Parisky K.M., Agosto J., Pulver S.R., Shang Y., Kuklin E., Hodge J.J.,
RA Kang K., Kang K., Liu X., Garrity P.A., Rosbash M., Griffith L.C.;
RT "PDF cells are a GABA-responsive wake-promoting component of the Drosophila
RT sleep circuit.";
RL Neuron 60:672-682(2008).
RN [15]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19230663; DOI=10.1016/j.cub.2009.01.040;
RA Chung B.Y., Kilman V.L., Keath J.R., Pitman J.L., Allada R.;
RT "The GABA(A) receptor RDL acts in peptidergic PDF neurons to promote sleep
RT in Drosophila.";
RL Curr. Biol. 19:386-390(2009).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19193904; DOI=10.1523/jneurosci.4763-08.2009;
RA Liu X., Buchanan M.E., Han K.A., Davis R.L.;
RT "The GABAA receptor RDL suppresses the conditioned stimulus pathway for
RT olfactory learning.";
RL J. Neurosci. 29:1573-1579(2009).
RN [17]
RP FUNCTION, INTERACTION WITH NLG4, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=24068821; DOI=10.1523/jneurosci.0819-13.2013;
RA Li Y., Zhou Z., Zhang X., Tong H., Li P., Zhang Z.C., Jia Z., Xie W.,
RA Han J.;
RT "Drosophila neuroligin 4 regulates sleep through modulating GABA
RT transmission.";
RL J. Neurosci. 33:15545-15554(2013).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24241395; DOI=10.1038/nn.3581;
RA Yuan Q., Song Y., Yang C.H., Jan L.Y., Jan Y.N.;
RT "Female contact modulates male aggression via a sexually dimorphic
RT GABAergic circuit in Drosophila.";
RL Nat. Neurosci. 17:81-88(2014).
RN [19]
RP FUNCTION (ISOFORM D), ACTIVITY REGULATION (ISOFORM D), MUTAGENESIS OF
RP ALA-301, AND CHARACTERIZATION OF VARIANT-283.
RX PubMed=24823815; DOI=10.1371/journal.pone.0097468;
RA Lees K., Musgaard M., Suwanmanee S., Buckingham S.D., Biggin P.,
RA Sattelle D.;
RT "Actions of agonists, fipronil and ivermectin on the predominant in vivo
RT splice and edit variant (RDLbd, I/V) of the Drosophila GABA receptor
RT expressed in Xenopus laevis oocytes.";
RL PLoS ONE 9:e97468-e97468(2014).
RN [20]
RP FUNCTION, INTERACTION WITH FBXL4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INDUCTION BY NEURONAL ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29174887; DOI=10.1016/j.cub.2017.10.052;
RA Li Q., Li Y., Wang X., Qi J., Jin X., Tong H., Zhou Z., Zhang Z.C., Han J.;
RT "Fbxl4 Serves as a Clock Output Molecule that Regulates Sleep through
RT Promotion of Rhythmic Degradation of the GABAA Receptor.";
RL Curr. Biol. 27:3616-3625.e5(2017).
RN [21]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=31535971; DOI=10.7554/elife.49373;
RA Molina-Obando S., Vargas-Fique J.F., Henning M., Guer B., Schladt T.M.,
RA Akhtar J., Berger T.K., Silies M.;
RT "ON selectivity in the Drosophila visual system is a multisynaptic process
RT involving both glutamatergic and GABAergic inhibition.";
RL Elife 8:0-0(2019).
RN [22]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32075756; DOI=10.1016/j.celrep.2020.01.061;
RA Keles M.F., Hardcastle B.J., Staedele C., Xiao Q., Frye M.A.;
RT "Inhibitory Interactions and Columnar Inputs to an Object Motion Detector
RT in Drosophila.";
RL Cell Rep. 30:2115-2124.e5(2020).
RN [23]
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF ALA-301.
RX PubMed=32339168; DOI=10.1371/journal.pgen.1008727;
RA Maurer G.W., Malita A., Nagy S., Koyama T., Werge T.M., Halberg K.A.,
RA Texada M.J., Rewitz K.;
RT "Analysis of genes within the schizophrenia-linked 22q11.2 deletion
RT identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep
RT control.";
RL PLoS Genet. 16:e1008727-e1008727(2020).
CC -!- FUNCTION: Gamma-aminobutyric acid (GABA) receptor voltage channel
CC subunit (PubMed:8016117, PubMed:8389005, PubMed:7527461,
CC PubMed:8882620, PubMed:12805302, PubMed:24823815). GABA, an inhibitory
CC neurotransmitter, mediates neuronal inhibition by binding to the GABA
CC receptor and opening an integral chloride channel (PubMed:8389005,
CC PubMed:7527461, PubMed:12805302). Together with glutamate receptor
CC GluClalpha, plays an important role in the visual response by
CC regulating the activity of ON/OFF-selective neurons (PubMed:31535971,
CC PubMed:32075756). Plays a role in promoting sleep and sleep latency by
CC regulating the activity of peptidergic PDF neurons (PubMed:18223647,
CC PubMed:19038223, PubMed:19230663). In large ventral lateral clock
CC neurons, clustering is mediated by Nlg4 and protein levels undergo
CC daily degradation in response to the circadian clock (PubMed:24068821,
CC PubMed:29174887). In neurons in the mushroom bodies, has a role in odor
CC memory acquisition where it inhibits appetitive and aversive olfactory
CC learning, probably upstream of adenylyl cyclase rut and GTPase
CC activating protein Nf1 (PubMed:18093529, PubMed:19193904). In male-
CC specific GABAergic neurons, plays a role in inhibiting male aggressive
CC behavior during courtship (PubMed:24241395).
CC {ECO:0000269|PubMed:12805302, ECO:0000269|PubMed:18093529,
CC ECO:0000269|PubMed:18223647, ECO:0000269|PubMed:19038223,
CC ECO:0000269|PubMed:19193904, ECO:0000269|PubMed:19230663,
CC ECO:0000269|PubMed:24068821, ECO:0000269|PubMed:24241395,
CC ECO:0000269|PubMed:24823815, ECO:0000269|PubMed:29174887,
CC ECO:0000269|PubMed:31535971, ECO:0000269|PubMed:32075756,
CC ECO:0000269|PubMed:7527461, ECO:0000269|PubMed:8016117,
CC ECO:0000269|PubMed:8389005, ECO:0000269|PubMed:8882620}.
CC -!- FUNCTION: [Isoform D]: Gamma-aminobutyric acid (GABA) receptor voltage
CC channel subunit. {ECO:0000269|PubMed:24823815}.
CC -!- ACTIVITY REGULATION: Activated by agonist muscimol (PubMed:8016117,
CC PubMed:12805302, PubMed:8389005, PubMed:24823815). Insensitive to zinc,
CC glycine, glutamate, and baclofen, loreclezole, to antagonist
CC bicuculline, glycine-receptor antagonist strychnine, and nonselective
CC GABA and glycine antagonist RU 5135 (PubMed:8016117, PubMed:8389005,
CC PubMed:8882620, PubMed:12805302). Insensitive to flunitrazepam,
CC pentobarbitone or pregnane steroids such as 5alpha-pregnan-3alpha-ol-
CC 20-one (PubMed:8016117, PubMed:8882620, PubMed:12805302). Inhibited by
CC insecticides picrotoxin (PTX), cyclodiene dieldrin, TBPS and lindane
CC (PubMed:8016117, PubMed:8389005, PubMed:7527461). Inhibited by
CC ivermectin, fipronil and pyrafluprole (PubMed:24823815).
CC {ECO:0000269|PubMed:12805302, ECO:0000269|PubMed:24823815,
CC ECO:0000269|PubMed:7527461, ECO:0000269|PubMed:8016117,
CC ECO:0000269|PubMed:8389005, ECO:0000269|PubMed:8882620}.
CC -!- ACTIVITY REGULATION: [Isoform D]: Inhibited by insecticides picrotoxin
CC (PTX). {ECO:0000269|PubMed:24823815}.
CC -!- SUBUNIT: Forms oligomers (PubMed:8882620). Interacts with Nlg4; the
CC interaction mediates Rdl clustering (PubMed:24068821). Interacts with
CC Fbxl4; the interaction mediates Rdl degradation (PubMed:29174887).
CC {ECO:0000269|PubMed:24068821, ECO:0000269|PubMed:29174887,
CC ECO:0000269|PubMed:8882620}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24068821,
CC ECO:0000269|PubMed:29174887}; Multi-pass membrane protein
CC {ECO:0000255}. Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:P15431}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P15431}. Cell projection, dendrite
CC {ECO:0000269|PubMed:18093529}. Cell projection, axon
CC {ECO:0000269|PubMed:18093529, ECO:0000269|PubMed:24068821}.
CC Note=Localizes to large ventral lateral clock neurons axonal
CC varicosities which are synaptic inputs to ventral lateral neuron
CC dendrites. {ECO:0000269|PubMed:24068821}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A; Synonyms=F;
CC IsoId=P25123-2; Sequence=Displayed;
CC Name=C;
CC IsoId=P25123-1; Sequence=VSP_054455, VSP_054456;
CC Name=D {ECO:0000303|PubMed:24823815}; Synonyms=B
CC {ECO:0000303|PubMed:24823815};
CC IsoId=P25123-3; Sequence=VSP_054456, VSP_054457, VSP_054458;
CC -!- TISSUE SPECIFICITY: Expressed in different parts of the brain: the
CC mushroom bodies (alpha, alpha', beta, beta', gamma lobes and
CC peduncles), the neurons projecting to the columnar-type neuron LC9
CC optic glomerulus, in interneurons connecting the paired olfactory
CC lobes, antennal lobes, PDF-expressing small and large ventral lateral
CC neurons (LNvs) of the circadian clock and lobula columnar neuron 11
CC (LC11) (at protein level) (PubMed:18093529, PubMed:19038223,
CC PubMed:32339168, PubMed:19230663, PubMed:24068821, PubMed:29174887,
CC PubMed:32075756). Expressed in all major ON pathway medulla neurons
CC (Mi1, Tm3, Mi4, and Mi9) and in OFF pathway neurons (Tm1, Tm2, Tm4, and
CC Tm9) (PubMed:31535971). {ECO:0000269|PubMed:18093529,
CC ECO:0000269|PubMed:19038223, ECO:0000269|PubMed:19230663,
CC ECO:0000269|PubMed:24068821, ECO:0000269|PubMed:29174887,
CC ECO:0000269|PubMed:31535971, ECO:0000269|PubMed:32075756,
CC ECO:0000269|PubMed:32339168}.
CC -!- INDUCTION: In large ventral lateral neurons (lLNvs), undergoes daily
CC rhythmic degradation which is inversely correlated with the activity of
CC lLNvs, which is involved in the circadian clock (PubMed:29174887).
CC Degradation levels are increased in the early hours of the morning and
CC mediated by the E3 ubiquitin ligase Fbxl4 (PubMed:29174887).
CC {ECO:0000269|PubMed:29174887}.
CC -!- RNA EDITING: Modified_positions=122 {ECO:0000269|PubMed:12907802,
CC ECO:0000269|PubMed:8016117}, 283 {ECO:0000269|PubMed:12537569,
CC ECO:0000269|PubMed:12907802, ECO:0000269|PubMed:1651498,
CC ECO:0000269|PubMed:8016117}, 294 {ECO:0000269|PubMed:12907802}, 360
CC {ECO:0000269|PubMed:12907802, ECO:0000269|PubMed:8016117};
CC Note=Partially edited.;
CC -!- DISRUPTION PHENOTYPE: In lobula columnar neurons 11 (LC11) results in a
CC reduction of visual responses to the motion of small objects
CC (PubMed:32075756). RNAi-mediated knockdown in neurons leads to dis-
CC inhibition of male aggressive behavior (PubMed:24241395). RNAi-mediated
CC knockdown in neurons in the alpha/beta mushroom bodies enhances
CC learning (PubMed:18093529). RNAi-mediated knockdown in mushroom bodies
CC enhances appetitive olfactory learning (PubMed:19193904). RNAi-mediated
CC knockdown in PDF-expressing neurons results in decreased sleep but does
CC not alter waking activity, circadian period, or rhythmicity under dark-
CC dark conditions (PubMed:19230663). Simultaneous knockout of adenylate
CC cyclase rut does not enhance the phenotype (PubMed:19193904).
CC Simultaneous knockout of E3 ligase Fbxl4 results in significantly
CC increased duration of daytime sleep and nighttime sleep as well as
CC shortened sleep onset latency (PubMed:29174887).
CC {ECO:0000269|PubMed:18093529, ECO:0000269|PubMed:19193904,
CC ECO:0000269|PubMed:19230663, ECO:0000269|PubMed:24241395,
CC ECO:0000269|PubMed:29174887, ECO:0000269|PubMed:32075756}.
CC -!- MISCELLANEOUS: Resistance is thought to be due to insensitivity of the
CC cyclodiene/picrotoxinin binding site on the GABA(A) receptor-chloride
CC ionophore complex.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28557.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA28558.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK92842.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M69057; AAA28556.1; -; mRNA.
DR EMBL; M69057; AAA28557.1; ALT_INIT; mRNA.
DR EMBL; M69057; AAA28558.1; ALT_INIT; mRNA.
DR EMBL; U02042; AAA19249.1; -; mRNA.
DR EMBL; AE014296; AAF50311.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11988.1; -; Genomic_DNA.
DR EMBL; AE014296; AAN11989.2; -; Genomic_DNA.
DR EMBL; AY051418; AAK92842.1; ALT_FRAME; mRNA.
DR EMBL; S61113; AAB26669.1; -; mRNA.
DR PIR; A41145; A41145.
DR RefSeq; NP_001261616.1; NM_001274687.1. [P25123-2]
DR RefSeq; NP_523991.2; NM_079267.4. [P25123-2]
DR RefSeq; NP_729461.1; NM_168321.3. [P25123-1]
DR RefSeq; NP_729462.2; NM_168322.3. [P25123-3]
DR AlphaFoldDB; P25123; -.
DR SMR; P25123; -.
DR BioGRID; 64454; 7.
DR STRING; 7227.FBpp0305970; -.
DR TCDB; 1.A.9.5.11; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; P25123; 2 sites.
DR PaxDb; P25123; -.
DR EnsemblMetazoa; FBtr0076534; FBpp0076261; FBgn0004244. [P25123-2]
DR EnsemblMetazoa; FBtr0076536; FBpp0076263; FBgn0004244. [P25123-1]
DR EnsemblMetazoa; FBtr0309054; FBpp0301075; FBgn0004244. [P25123-3]
DR EnsemblMetazoa; FBtr0333835; FBpp0305969; FBgn0004244. [P25123-2]
DR GeneID; 39054; -.
DR KEGG; dme:Dmel_CG10537; -.
DR CTD; 39054; -.
DR FlyBase; FBgn0004244; Rdl.
DR VEuPathDB; VectorBase:FBgn0004244; -.
DR eggNOG; KOG3643; Eukaryota.
DR GeneTree; ENSGT00940000169322; -.
DR InParanoid; P25123; -.
DR OMA; IRYKWNA; -.
DR Reactome; R-DME-977443; GABA receptor activation.
DR BioGRID-ORCS; 39054; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 39054; -.
DR PRO; PR:P25123; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0004244; Expressed in second segment of antenna (Drosophila) and 8 other tissues.
DR ExpressionAtlas; P25123; baseline and differential.
DR Genevisible; P25123; DM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:FlyBase.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IDA:FlyBase.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0032589; C:neuron projection membrane; IDA:FlyBase.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; ISS:FlyBase.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004890; F:GABA-A receptor activity; TAS:FlyBase.
DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IDA:FlyBase.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IDA:UniProtKB.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0002121; P:inter-male aggressive behavior; IMP:FlyBase.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; IDA:UniProtKB.
DR GO; GO:0050805; P:negative regulation of synaptic transmission; IMP:FlyBase.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0042048; P:olfactory behavior; IMP:FlyBase.
DR GO; GO:0042749; P:regulation of circadian sleep/wake cycle; IMP:FlyBase.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0090328; P:regulation of olfactory learning; IMP:FlyBase.
DR GO; GO:0009612; P:response to mechanical stimulus; IGI:FlyBase.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:FlyBase.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0030431; P:sleep; IMP:FlyBase.
DR Gene3D; 1.20.58.390; -; 2.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR002289; GABAAb_rcpt.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR InterPro; IPR006201; Neur_channel.
DR InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR InterPro; IPR038050; Neuro_actylchol_rec.
DR InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR PANTHER; PTHR18945; PTHR18945; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR01160; GABAARBETA.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR00252; NRIONCHANNEL.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Chloride;
KW Chloride channel; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Receptor;
KW Reference proteome; RNA editing; Signal; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..44
FT /evidence="ECO:0000255"
FT CHAIN 45..606
FT /note="Gamma-aminobutyric acid receptor subunit beta"
FT /id="PRO_0000000452"
FT TOPO_DOM 45..268
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 333..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..568
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 569..590
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 376..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 482..542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 376..393
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 185..199
FT /evidence="ECO:0000250"
FT VAR_SEQ 97..101
FT /note="LSEVK -> VSEVL (in isoform C)"
FT /evidence="ECO:0000303|PubMed:1651498"
FT /id="VSP_054455"
FT VAR_SEQ 216..248
FT /note="KWNEGPNSVGVSSEVSLPQFKVLGHRQRAMEIS -> FWRDGLSSVGMSSEV
FT ELPQFRVLGHRQRATEIN (in isoform C and isoform D)"
FT /evidence="ECO:0000303|PubMed:12537569,
FT ECO:0000303|PubMed:1651498"
FT /id="VSP_054456"
FT VAR_SEQ 448..476
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_054457"
FT VAR_SEQ 552
FT /note="K -> KKV (in isoform D)"
FT /evidence="ECO:0000303|PubMed:12537569"
FT /id="VSP_054458"
FT VARIANT 122
FT /note="R -> G (in RNA edited version)"
FT /evidence="ECO:0000269|PubMed:8016117,
FT ECO:0000269|PubMed:8389005"
FT VARIANT 283
FT /note="I -> V (in RNA edited version; does not alter GABA
FT receptor activity; retains inhibition by picrotoxin; shows
FT resistance to picrotoxinin; when associated with S-301)"
FT /evidence="ECO:0000269|PubMed:12537569,
FT ECO:0000269|PubMed:1651498, ECO:0000269|PubMed:24823815,
FT ECO:0000269|PubMed:8016117, ECO:0000269|PubMed:8389005"
FT VARIANT 294
FT /note="N -> D (in RNA edited version)"
FT /evidence="ECO:0000269|PubMed:8389005"
FT VARIANT 360
FT /note="M -> V (in RNA edited version)"
FT /evidence="ECO:0000269|PubMed:8016117,
FT ECO:0000269|PubMed:8389005"
FT MUTAGEN 301
FT /note="A->S: Reduces in-current for inward flow of chloride
FT ions, results in slower and incomplete desensitization
FT which ultimately increases single channel open durations.
FT Resistant to picrotoxinin (PTX) and cyclodiene dieldrin
FT insecticides. Retains partial sensitivity to TBPS and
FT lindane. Decreases sleep latency, increases total sleep
FT time and shows resistance to carbamazepine sleep-induced
FT effects on sleep both by itself or when associated with I-
FT 360. Restores defective sleep in Nlg4 and Lztr1 mutants.
FT Retains resistance to picrotoxinin; when associated with V-
FT 283."
FT /evidence="ECO:0000269|PubMed:18223647,
FT ECO:0000269|PubMed:24068821, ECO:0000269|PubMed:24823815,
FT ECO:0000269|PubMed:32339168, ECO:0000269|PubMed:7527461,
FT ECO:0000269|PubMed:8389005"
FT MUTAGEN 360
FT /note="M->I: Decreases sleep latency; when associated with
FT S-301."
FT /evidence="ECO:0000269|PubMed:18223647"
FT CONFLICT 38
FT /note="H -> N (in Ref. 2; AAA19249)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="V -> I (in Ref. 2; AAA19249)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="G -> R (in Ref. 2; AAA19249)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 606 AA; 65656 MW; 25BDDCB03DAD54F8 CRC64;
MSDSKMDKLA RMAPLPRTPL LTIWLAINMA LIAQETGHKR IHTVQAATGG GSMLGDVNIS
AILDSFSVSY DKRVRPNYGG PPVEVGVTMY VLSISSLSEV KMDFTLDFYF RQFWTDPRLA
YRKRPGVETL SVGSEFIKNI WVPDTFFVNE KQSYFHIATT SNEFIRVHHS GSITRSIRLT
ITASCPMNLQ YFPMDRQLCH IEIESFGYTM RDIRYKWNEG PNSVGVSSEV SLPQFKVLGH
RQRAMEISLT TGNYSRLACE IQFVRSMGYY LIQIYIPSGL IVIISWVSFW LNRNATPARV
ALGVTTVLTM TTLMSSTNAA LPKISYVKSI DVYLGTCFVM VFASLLEYAT VGYMAKRIQM
RKQRFMAIQK IAEQKKQQLD GANQQQANPN PNANVGGPGG VGVGPGGPGG PGGGVNVGVG
MGMGPEHGHG HGHHAHSHGH PHAPKQTVSN RPIGFSNIQQ NVGTRGCSIV GPLFQEVRFK
VHDPKAHSKG GTLENTVNGG RGGPQSHGPG PGQGGGPPGG GGGGGGGGGP PEGGGDPEAA
VPAHLLHPGK VKKDINKLLG ITPSDIDKYS RIVFPVCFVC FNLMYWIIYL HVSDVVADDL
VLLGEE
