NPFR_DROME
ID NPFR_DROME Reviewed; 485 AA.
AC Q9VNM1; D2CFP0; D2CFP1; D2CFP2; D2CFP3; D2CFP4; Q7KFF8; Q8SZ35; Q967T7;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Neuropeptide F receptor {ECO:0000303|PubMed:11897397, ECO:0000312|EMBL:AAF51909.3};
DE Short=DmNPFR1 {ECO:0000303|PubMed:11897397};
GN Name=NPFR {ECO:0000312|FlyBase:FBgn0037408}; Synonyms=NPFR1;
GN ORFNames=CG1147;
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] {ECO:0000305, ECO:0000312|EMBL:AAK50050.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), FUNCTION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RC TISSUE=Larva {ECO:0000269|PubMed:11897397};
RX PubMed=11897397; DOI=10.1016/s0196-9781(01)00647-7;
RA Garczynski S.F., Brown M.R., Shen P., Murray T.F., Crim J.W.;
RT "Characterization of a functional neuropeptide F receptor from Drosophila
RT melanogaster.";
RL Peptides 23:773-780(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:ABH01175.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; A; B; C AND D).
RA Joergensen L.M., Grimmelikhuijzen C.J.P.;
RT "Molecular cloning of splice variant 1 of DmNPFR1.";
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAF51909.3}
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] {ECO:0000305, ECO:0000312|EMBL:AAF51909.3}
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] {ECO:0000305, ECO:0000312|EMBL:ABH01175.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL48774.1}; TISSUE=Embryo;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:ABH01175.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL48774.1};
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15677721; DOI=10.1073/pnas.0406814102;
RA Wen T., Parrish C.A., Xu D., Wu Q., Shen P.;
RT "Drosophila neuropeptide F and its receptor, NPFR1, define a signaling
RT pathway that acutely modulates alcohol sensitivity.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:2141-2146(2005).
RN [8] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19837040; DOI=10.1016/j.cell.2009.08.035;
RA Krashes M.J., DasGupta S., Vreede A., White B., Armstrong J.D., Waddell S.;
RT "A neural circuit mechanism integrating motivational state with memory
RT expression in Drosophila.";
RL Cell 139:416-427(2009).
RN [9] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20164335; DOI=10.1523/jneurosci.3262-09.2010;
RA Xu J., Li M., Shen P.;
RT "A G-protein-coupled neuropeptide Y-like receptor suppresses behavioral and
RT sensory response to multiple stressful stimuli in Drosophila.";
RL J. Neurosci. 30:2504-2512(2010).
RN [10] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22422983; DOI=10.1126/science.1215932;
RA Shohat-Ophir G., Kaun K.R., Azanchi R., Heberlein U.;
RT "Sexual deprivation increases ethanol intake in Drosophila.";
RL Science 335:1351-1355(2012).
CC -!- FUNCTION: Receptor for NPF. Integral part of the sensory system that
CC mediates food signaling, providing the neural basis for the regulation
CC of food response; coordinates larval foraging and social behavior
CC changes during development. Required in dopaminergic (DA) neurons that
CC innervate the mushroom body for satiety to suppress appetitive memory
CC performance; a key factor in the internal state of hunger in the brain.
CC NPF neurons coordinately modulate diverse sensory and motor neurons
CC important for feeding, flight, and locomotion. NPF/NPFR pathway exerts
CC its suppressive effect on larval aversion to diverse stressful stimuli
CC (chemical stress and noxious heat) through attenuation of TRP channel-
CC induced neuronal excitation. NPF neural signaling system plays a
CC physiological role in acute modulation of alcohol sensitivity in
CC adults, rather than a general response to intoxication by sedative
CC agents. Activation and inhibition of the NPF system reduces and
CC enhances ethanol preference, respectively. Sexual experience, the NPF
CC system activity and ethanol consumption are all linked; sexual
CC deprivation is a major contributor to enhanced ethanol preference.
CC {ECO:0000269|PubMed:11897397, ECO:0000269|PubMed:15677721,
CC ECO:0000269|PubMed:19837040, ECO:0000269|PubMed:20164335,
CC ECO:0000269|PubMed:22422983}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=A {ECO:0000269|PubMed:10731132}; Synonyms=variant 1
CC {ECO:0000269|Ref.2};
CC IsoId=Q9VNM1-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|Ref.2};
CC IsoId=Q9VNM1-2; Sequence=VSP_043735, VSP_043736;
CC Name=B {ECO:0000269|PubMed:10731132}; Synonyms=variant 3
CC {ECO:0000269|Ref.2};
CC IsoId=Q9VNM1-3; Sequence=VSP_043736, VSP_043737;
CC Name=D {ECO:0000269|PubMed:10731132}; Synonyms=variant 4
CC {ECO:0000269|Ref.2};
CC IsoId=Q9VNM1-4; Sequence=VSP_043737;
CC Name=C {ECO:0000269|PubMed:10731132}; Synonyms=variant 5
CC {ECO:0000269|Ref.2};
CC IsoId=Q9VNM1-5; Sequence=VSP_043736;
CC Name=6 {ECO:0000269|PubMed:10731132, ECO:0000269|PubMed:11897397};
CC IsoId=Q9VNM1-6; Sequence=VSP_043735;
CC -!- TISSUE SPECIFICITY: Expressed in midgut, brain lobes and ventral nerve
CC cord of larvae. In adults, expressed in a pair of dorsolateral neurons
CC in the protocerebrum, and the central complex and a small number of
CC neurons in the subesophageal ganglion (at protein level). Expressed in
CC a subset of sugar-responsive PAIN neurons in the thoracic body but is
CC absent from other peripheral PAIN neurons.
CC {ECO:0000269|PubMed:11897397, ECO:0000269|PubMed:15677721,
CC ECO:0000269|PubMed:19837040, ECO:0000269|PubMed:20164335,
CC ECO:0000269|PubMed:22422983}.
CC -!- DISRUPTION PHENOTYPE: Increased NPF or NPFR activity dominantly
CC suppresses PAIN-mediated food aversion in postfeeding larvae.
CC Deficiency in NPF/NPFR signaling causes decreased alcohol sensitivity
CC and overexpression causes a hypersensitive response to alcohol
CC sedation. Controlled functional disruption of NPF or NPFR neurons
CC rapidly triggers acute resistance to ethanol sedation.
CC {ECO:0000269|PubMed:11897397, ECO:0000269|PubMed:15677721,
CC ECO:0000269|PubMed:20164335, ECO:0000269|PubMed:22422983}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF364400; AAK50050.1; -; mRNA.
DR EMBL; DQ666847; ABH01175.1; -; mRNA.
DR EMBL; DQ666848; ABH01176.1; -; mRNA.
DR EMBL; DQ666849; ABH01177.1; -; mRNA.
DR EMBL; DQ666850; ABH01178.1; -; mRNA.
DR EMBL; DQ666851; ABH01179.1; -; mRNA.
DR EMBL; AE014297; AAF51909.3; -; Genomic_DNA.
DR EMBL; AY071152; AAL48774.1; -; mRNA.
DR EMBL; BT044552; ACI12877.1; -; mRNA.
DR RefSeq; NP_001246946.1; NM_001260017.2. [Q9VNM1-5]
DR RefSeq; NP_524245.3; NM_079521.4. [Q9VNM1-1]
DR AlphaFoldDB; Q9VNM1; -.
DR SMR; Q9VNM1; -.
DR IntAct; Q9VNM1; 1.
DR STRING; 7227.FBpp0300637; -.
DR ChEMBL; CHEMBL3879841; -.
DR PaxDb; Q9VNM1; -.
DR PRIDE; Q9VNM1; -.
DR DNASU; 40754; -.
DR EnsemblMetazoa; FBtr0078590; FBpp0078239; FBgn0037408. [Q9VNM1-1]
DR EnsemblMetazoa; FBtr0308316; FBpp0300635; FBgn0037408. [Q9VNM1-3]
DR EnsemblMetazoa; FBtr0308317; FBpp0300636; FBgn0037408. [Q9VNM1-5]
DR EnsemblMetazoa; FBtr0308318; FBpp0300637; FBgn0037408. [Q9VNM1-4]
DR GeneID; 40754; -.
DR KEGG; dme:Dmel_CG1147; -.
DR UCSC; CG1147-RA; d. melanogaster. [Q9VNM1-1]
DR CTD; 40754; -.
DR FlyBase; FBgn0037408; NPFR.
DR VEuPathDB; VectorBase:FBgn0037408; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00940000168939; -.
DR InParanoid; Q9VNM1; -.
DR OMA; CSEPTNV; -.
DR PhylomeDB; Q9VNM1; -.
DR BioGRID-ORCS; 40754; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40754; -.
DR PRO; PR:Q9VNM1; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037408; Expressed in oviduct (Drosophila) and 19 other tissues.
DR ExpressionAtlas; Q9VNM1; baseline and differential.
DR Genevisible; Q9VNM1; DM.
DR GO; GO:0016021; C:integral component of membrane; ISS:FlyBase.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:FlyBase.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042923; F:neuropeptide binding; IPI:FlyBase.
DR GO; GO:0042263; F:neuropeptide F receptor activity; IPI:FlyBase.
DR GO; GO:0008188; F:neuropeptide receptor activity; IBA:GO_Central.
DR GO; GO:0004983; F:neuropeptide Y receptor activity; IEA:InterPro.
DR GO; GO:0038002; P:endocrine signaling; IMP:FlyBase.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISM:FlyBase.
DR GO; GO:0030536; P:larval feeding behavior; IMP:FlyBase.
DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; IDA:FlyBase.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:FlyBase.
DR GO; GO:0042048; P:olfactory behavior; IMP:FlyBase.
DR GO; GO:1990834; P:response to odorant; IMP:FlyBase.
DR GO; GO:0007217; P:tachykinin receptor signaling pathway; ISS:FlyBase.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000611; NPY_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01012; NRPEPTIDEYR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Behavior; Disulfide bond; G-protein coupled receptor;
KW Membrane; Neuropeptide; Receptor; Reference proteome; Stress response;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..485
FT /note="Neuropeptide F receptor"
FT /id="PRO_0000417447"
FT TOPO_DOM 1..91
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..112
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..122
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..163
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..202
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 224..262
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..317
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..355
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 377..485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DISULFID 161..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1..4
FT /note="Missing (in isoform 2 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11897397, ECO:0000303|Ref.2"
FT /id="VSP_043735"
FT VAR_SEQ 382..404
FT /note="Missing (in isoform 2, isoform B and isoform C)"
FT /evidence="ECO:0000303|PubMed:10731132, ECO:0000303|Ref.2"
FT /id="VSP_043736"
FT VAR_SEQ 485
FT /note="R -> RLEQY (in isoform B and isoform D)"
FT /evidence="ECO:0000303|PubMed:10731132, ECO:0000303|Ref.2"
FT /id="VSP_043737"
FT CONFLICT 65
FT /note="R -> M (in Ref. 5; AAL48774)"
FT /evidence="ECO:0000305"
FT CONFLICT 162
FT /note="K -> E (in Ref. 2; ABH01175)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="M -> V (in Ref. 2; ABH01178)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="R -> W (in Ref. 2; ABH01178)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="A -> T (in Ref. 2; ABH01177)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="V -> A (in Ref. 2; ABH01175)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="R -> K (in Ref. 2; ABH01177)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 485 AA; 53537 MW; 8E92C4A83BE08DC8 CRC64;
MIISMNQTEP AQLADGEHLS GYASSSNSVR YLDDRHPLDY LDLGTVHALN TTAINTSDLN
ETGSRPLDPV LIDRFLSNRA VDSPWYHMLI SMYGVLIVFG ALGNTLVVIA VIRKPIMRTA
RNLFILNLAI SDLLLCLVTM PLTLMEILSK YWPYGSCSIL CKTIAMLQAL CIFVSTISIT
AIAFDRYQVI VYPTRDSLQF VGAVTILAGI WALALLLASP LFVYKELINT DTPALLQQIG
LQDTIPYCIE DWPSRNGRFY YSIFSLCVQY LVPILIVSVA YFGIYNKLKS RITVVAVQAS
SAQRKVERGR RMKRTNCLLI SIAIIFGVSW LPLNFFNLYA DMERSPVTQS MLVRYAICHM
IGMSSACSNP LLYGWLNDNF RKEFQELLCR CSDTNVALNG HTTGCNVQAA ARRRRKLGAE
LSKGELKLLG PGGAQSGTAG GEGGLAATDF MTGHHEGGLR SAITESVALT DHNPVPSEVT
KLMPR
