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GR66A_DROME
ID   GR66A_DROME             Reviewed;         527 AA.
AC   Q9VSH2;
DT   02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   21-SEP-2011, sequence version 3.
DT   03-AUG-2022, entry version 141.
DE   RecName: Full=Gustatory receptor for bitter taste 66a;
GN   Name=Gr66a; ORFNames=CG7189;
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 [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   [2]
RP   GENOME REANNOTATION.
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   [3]
RP   IDENTIFICATION, AND TISSUE SPECIFICITY.
RX   PubMed=11516643; DOI=10.1016/s0960-9822(01)00258-5;
RA   Dunipace L., Meister S., McNealy C., Amrein H.;
RT   "Spatially restricted expression of candidate taste receptors in the
RT   Drosophila gustatory system.";
RL   Curr. Biol. 11:822-835(2001).
RN   [4]
RP   TISSUE SPECIFICITY, AND FUNCTION.
RX   PubMed=15202999; DOI=10.1016/j.cub.2004.05.019;
RA   Thorne N., Chromey C., Bray S., Amrein H.;
RT   "Taste perception and coding in Drosophila.";
RL   Curr. Biol. 14:1065-1079(2004).
RN   [5]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX   PubMed=16979558; DOI=10.1016/j.cub.2006.07.024;
RA   Moon S.J., Kottgen M., Jiao Y., Xu H., Montell C.;
RT   "A taste receptor required for the caffeine response in vivo.";
RL   Curr. Biol. 16:1812-1817(2006).
RN   [6]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=16423701; DOI=10.1016/j.neuron.2005.11.037;
RA   Marella S., Fischler W., Kong P., Asgarian S., Rueckert E., Scott K.;
RT   "Imaging taste responses in the fly brain reveals a functional map of taste
RT   category and behavior.";
RL   Neuron 49:285-295(2006).
RN   [7]
RP   FUNCTION.
RX   PubMed=19618260; DOI=10.1007/s10519-009-9286-8;
RA   Lacaille F., Everaerts C., Ferveur J.F.;
RT   "Feminization and alteration of Drosophila taste neurons induce reciprocal
RT   effects on male avoidance behavior.";
RL   Behav. Genet. 39:554-563(2009).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=19246397; DOI=10.1073/pnas.0811744106;
RA   Lee Y., Moon S.J., Montell C.;
RT   "Multiple gustatory receptors required for the caffeine response in
RT   Drosophila.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:4495-4500(2009).
RN   [9]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=20797533; DOI=10.1016/j.neuron.2010.07.006;
RA   Lee Y., Kim S.H., Montell C.;
RT   "Avoiding DEET through insect gustatory receptors.";
RL   Neuron 67:555-561(2010).
RN   [10]
RP   TISSUE SPECIFICITY.
RX   PubMed=22031876; DOI=10.1523/jneurosci.3363-11.2011;
RA   Kwon J.Y., Dahanukar A., Weiss L.A., Carlson J.R.;
RT   "Molecular and cellular organization of the taste system in the Drosophila
RT   larva.";
RL   J. Neurosci. 31:15300-15309(2011).
RN   [11]
RP   FUNCTION.
RX   PubMed=22798487; DOI=10.1534/genetics.112.142455;
RA   Joseph R.M., Heberlein U.;
RT   "Tissue-specific activation of a single gustatory receptor produces
RT   opposing behavioral responses in Drosophila.";
RL   Genetics 192:521-532(2012).
RN   [12]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22279227; DOI=10.1523/jneurosci.4630-11.2012;
RA   Lee Y., Kang M.J., Shim J., Cheong C.U., Moon S.J., Montell C.;
RT   "Gustatory receptors required for avoiding the insecticide L-canavanine.";
RL   J. Neurosci. 32:1429-1435(2012).
CC   -!- FUNCTION: Gustatory receptor required for response to the bitter in
CC       taste neurons. Gr66a cells respond to bitter compounds such as
CC       caffeine, theophylline, threonine or valine. Flies avoid bitter
CC       substances, suggesting that Gr66a neuron activity is sufficient to
CC       mediate avoidance behavior. Required for sensing and avoiding N,N-
CC       Diethyl-meta-toluamide (DEET), the most widely used insect repellent
CC       worldwide, as well as to L-canavanine, a plant-derived insecticide.
CC       Gr66a neurons are also involved in the sex-specific perception of
CC       molecules inducing male avoidance behavior, probably through sensing 7-
CC       tricosene (7-T), a male cuticular pheromone and leading to inhibition
CC       of male-male courtship. Finally, also plays a role in oviposition
CC       behavior, in which females evaluate their environment and choose to lay
CC       eggs on substrates they may find aversive in other contexts.
CC       {ECO:0000269|PubMed:15202999, ECO:0000269|PubMed:16423701,
CC       ECO:0000269|PubMed:16979558, ECO:0000269|PubMed:19246397,
CC       ECO:0000269|PubMed:19618260, ECO:0000269|PubMed:20797533,
CC       ECO:0000269|PubMed:22279227, ECO:0000269|PubMed:22798487}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Taste hairs in labial palps, labral and cibarial
CC       sense organs and forelegs. In larvae, is expressed in neurons of the
CC       terminal external chemosensory organ, as well as in the dorsal,
CC       ventral, and posterior pharyngeal sense organs.
CC       {ECO:0000269|PubMed:11516643, ECO:0000269|PubMed:15202999,
CC       ECO:0000269|PubMed:16423701, ECO:0000269|PubMed:16979558,
CC       ECO:0000269|PubMed:22031876}.
CC   -!- DISRUPTION PHENOTYPE: Disrupts fly aversion to caffeine, N,N-Diethyl-
CC       meta-toluamide (DEET), and L-canavanine. {ECO:0000269|PubMed:16979558,
CC       ECO:0000269|PubMed:19246397, ECO:0000269|PubMed:20797533,
CC       ECO:0000269|PubMed:22279227}.
CC   -!- SIMILARITY: Belongs to the insect chemoreceptor superfamily. Gustatory
CC       receptor (GR) family. Gr66a subfamily. {ECO:0000305}.
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DR   EMBL; AE014296; AAF50447.3; -; Genomic_DNA.
DR   RefSeq; NP_523971.3; NM_079247.3.
DR   AlphaFoldDB; Q9VSH2; -.
DR   STRING; 7227.FBpp0289508; -.
DR   GlyGen; Q9VSH2; 2 sites.
DR   PaxDb; Q9VSH2; -.
DR   EnsemblMetazoa; FBtr0300280; FBpp0289508; FBgn0035870.
DR   GeneID; 38935; -.
DR   KEGG; dme:Dmel_CG7189; -.
DR   CTD; 38935; -.
DR   FlyBase; FBgn0035870; Gr66a.
DR   VEuPathDB; VectorBase:FBgn0035870; -.
DR   eggNOG; ENOG502S2QD; Eukaryota.
DR   GeneTree; ENSGT00940000166130; -.
DR   HOGENOM; CLU_555838_0_0_1; -.
DR   InParanoid; Q9VSH2; -.
DR   OMA; SWKTSQA; -.
DR   OrthoDB; 550351at2759; -.
DR   PhylomeDB; Q9VSH2; -.
DR   SignaLink; Q9VSH2; -.
DR   BioGRID-ORCS; 38935; 0 hits in 1 CRISPR screen.
DR   GenomeRNAi; 38935; -.
DR   PRO; PR:Q9VSH2; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0035870; Expressed in gustatory receptor neuron (Drosophila) and 4 other tissues.
DR   ExpressionAtlas; Q9VSH2; baseline and differential.
DR   Genevisible; Q9VSH2; DM.
DR   GO; GO:0030424; C:axon; IDA:FlyBase.
DR   GO; GO:0030425; C:dendrite; IDA:FlyBase.
DR   GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008527; F:taste receptor activity; NAS:UniProtKB.
DR   GO; GO:0007635; P:chemosensory behavior; IMP:FlyBase.
DR   GO; GO:0050912; P:detection of chemical stimulus involved in sensory perception of taste; NAS:UniProtKB.
DR   GO; GO:0031000; P:response to caffeine; IMP:FlyBase.
DR   GO; GO:0017085; P:response to insecticide; IMP:FlyBase.
DR   GO; GO:1901354; P:response to L-canavanine; IMP:FlyBase.
DR   GO; GO:0050913; P:sensory perception of bitter taste; IMP:FlyBase.
DR   GO; GO:0050909; P:sensory perception of taste; NAS:FlyBase.
DR   GO; GO:0007165; P:signal transduction; IEA:UniProtKB-KW.
DR   InterPro; IPR013604; 7TM_chemorcpt.
DR   PANTHER; PTHR21143; PTHR21143; 1.
DR   Pfam; PF08395; 7tm_7; 2.
PE   2: Evidence at transcript level;
KW   Cell membrane; Glycoprotein; Membrane; Receptor; Reference proteome;
KW   Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..527
FT                   /note="Gustatory receptor for bitter taste 66a"
FT                   /id="PRO_0000216535"
FT   TOPO_DOM        1..46
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        47..67
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        68..80
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        81..101
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        102..144
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        145..165
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        166..174
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        175..195
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        196..345
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        346..366
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        367..382
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        383..403
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        404..460
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        461..481
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        482..527
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        496
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        510
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   527 AA;  59081 MW;  E3C0F6335C89B232 CRC64;
     MAQAEDAVQP LLQQFQQLFF ISKIAGILPQ DLEKFRSRNL LEKSRNGMIY MLSTLILYVV
     LYNILIYSFG EEDRSLKASQ STLTFVIGLF LTYIGLIMMV SDQLTALRNQ GRIGELYERI
     RLVDERLYKE GCVMDNSTIG RRIRIMLIMT VIFELSILVS TYVKLVDYSQ WMSLLWIVSA
     IPTFINTLDK IWFAVSLYAL KERFEAINAT LEELVDTHEK HKLWLRGNQE VPPPLDSSQP
     PQYDSNLEYL YKELGGMDIG SIGKSSVSGS GKNKVAPVAH SMNSFGEAID AASRKPPPPP
     LATNMVHESE LGNAAKVEEK LNNLCQVHDE ICEIGKALNE LWSYPILSLM AYGFLIFTAQ
     LYFLYCATQY QSIPSLFRSA KNPFITVIVL SYTSGKCVYL IYLSWKTSQA SKRTGISLHK
     CGVVADDNLL YEIVNHLSLK LLNHSVDFSA CGFFTLDMET LYGVSGGITS YLIILIQFNL
     AAQQAKEAIQ TFNSLNDTAG LVGAATDMDN ISSTLRDFVT TTMTPAV
 
 
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