OX2R_CANLF
ID OX2R_CANLF Reviewed; 444 AA.
AC Q9TUP7;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Orexin receptor type 2;
DE Short=Ox-2-R;
DE Short=Ox2-R;
DE Short=Ox2R;
DE AltName: Full=Hypocretin receptor type 2;
GN Name=HCRTR2;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10458611; DOI=10.1016/s0092-8674(00)81965-0;
RA Lin L., Faraco J., Li R., Kadotani H., Rogers W., Lin X., Qiu X.,
RA de Jong P.J., Nishino S., Mignot E.;
RT "The sleep disorder canine narcolepsy is caused by a mutation in the
RT hypocretin receptor 2 gene.";
RL Cell 98:365-376(1999).
RN [2]
RP REVIEW.
RX PubMed=11340621; DOI=10.1002/bies.1058;
RA Hungs M., Mignot E.;
RT "Hypocretin/orexin, sleep and narcolepsy.";
RL Bioessays 23:397-408(2001).
RN [3]
RP REVIEW.
RX PubMed=11283317; DOI=10.1146/annurev.neuro.24.1.429;
RA Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M.;
RT "To eat or to sleep? Orexin in the regulation of feeding and wakefulness.";
RL Annu. Rev. Neurosci. 24:429-458(2001).
RN [4]
RP VARIANT NARCOLEPSY LYS-54, CHARACTERIZATION OF VARIANT LYS-54, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=11282968; DOI=10.1101/gr.gr-1610r;
RA Hungs M., Fan J., Lin L., Lin X., Maki R.A., Mignot E.;
RT "Identification and functional analysis of mutations in the hypocretin
RT (orexin) genes of narcoleptic canines.";
RL Genome Res. 11:531-539(2001).
CC -!- FUNCTION: Nonselective, high-affinity receptor for both orexin-A and
CC orexin-B neuropeptides. Triggers an increase in cytoplasmic Ca(2+)
CC levels in response to orexin-A binding. {ECO:0000269|PubMed:11282968}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11282968};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The N-terminal region is required for orexin signaling.
CC {ECO:0000250|UniProtKB:O43614}.
CC -!- DISEASE: Note=Defects in HCRTR2 are a cause of an autosomal recessive
CC form of narcolepsy, observed in labradors, dobermans and dachshunds.
CC Narcolepsy is a neurological sleep disorder affecting animals and
CC humans, characterized by excessive daytime sleepiness, sleep
CC fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep,
CC such as cataplexy, hypnagogic hallucinations, and sleep paralysis.
CC Cataplexy is a sudden loss of muscle tone triggered by emotions, which
CC is the most valuable clinical feature used to diagnose narcolepsy. As
CC in humans, most cases of canine narcolepsy are sporadic but an
CC autosomal recessive form was also observed.
CC {ECO:0000269|PubMed:10458611, ECO:0000269|PubMed:11282968}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF164626; AAD49333.1; -; mRNA.
DR RefSeq; NP_001002933.1; NM_001002933.1.
DR AlphaFoldDB; Q9TUP7; -.
DR SMR; Q9TUP7; -.
DR STRING; 9612.ENSCAFP00000003376; -.
DR ChEMBL; CHEMBL3337331; -.
DR PaxDb; Q9TUP7; -.
DR Ensembl; ENSCAFT00030028273; ENSCAFP00030024667; ENSCAFG00030015317.
DR Ensembl; ENSCAFT00040013762; ENSCAFP00040011917; ENSCAFG00040007394.
DR Ensembl; ENSCAFT00845020320; ENSCAFP00845015927; ENSCAFG00845011460.
DR GeneID; 399545; -.
DR KEGG; cfa:399545; -.
DR CTD; 3062; -.
DR VEuPathDB; HostDB:ENSCAFG00845011460; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230390; -.
DR HOGENOM; CLU_009579_6_3_1; -.
DR InParanoid; Q9TUP7; -.
DR OMA; AEVYPKM; -.
DR OrthoDB; 981089at2759; -.
DR TreeFam; TF315303; -.
DR Reactome; R-CFA-389397; Orexin and neuropeptides FF and QRFP bind to their respective receptors.
DR Reactome; R-CFA-416476; G alpha (q) signalling events.
DR Proteomes; UP000002254; Chromosome 12.
DR Bgee; ENSCAFG00000002328; Expressed in temporal lobe and 9 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0016499; F:orexin receptor activity; IDA:UniProtKB.
DR GO; GO:0022410; P:circadian sleep/wake cycle process; IEA:InterPro.
DR GO; GO:0007631; P:feeding behavior; IEA:InterPro.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0040011; P:locomotion; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0010840; P:regulation of circadian sleep/wake cycle, wakefulness; IMP:UniProtKB.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000204; Orexin_rcpt.
DR InterPro; IPR004060; Orexin_rcpt_2.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF03827; Orexin_rec2; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01522; OREXIN2R.
DR PRINTS; PR01064; OREXINR.
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 Cell membrane; Disease variant; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..444
FT /note="Orexin receptor type 2"
FT /id="PRO_0000069988"
FT TOPO_DOM 1..54
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 55..75
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 76..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 89..110
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 111..127
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 128..150
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 151..170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 171..191
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 192..222
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 223..243
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 244..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 305..326
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 327..342
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TRANSMEM 343..366
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT TOPO_DOM 367..444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 33..49
FT /note="Required for response to orexin-A"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT COMPBIAS 1..29
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 44
FT /note="Important for responses to orexin"
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT CARBOHYD 14
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 22
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 127..210
FT /evidence="ECO:0000250|UniProtKB:O43614"
FT VARIANT 54
FT /note="E -> K (in narcolepsy; autosomal recessive; loss of
FT function)"
FT /evidence="ECO:0000269|PubMed:11282968"
SQ SEQUENCE 444 AA; 50675 MW; D848A4536D485D6B CRC64;
MSGTKLEDSP PCRNWSSAPE LNETQEPFLN PTDYDDEEFL RYLWREYLHP KEYEWVLIAG
YIIVFVVALV GNVLVCVAVW KNHHMRTVTN YFIVNLSLAD VLVTITCLPA TLVVDITETW
FFGQSLCKVI PYLQTVSVSV SVLTLSCIAL DRWYAICHPL MFKSTAKRAR NSIVIIWIVS
CIIMIPQAIV MECSTMLPGL ANKTTLFTVC DERWGGEIYP KMYHICFFLV TYMAPLCLMV
LAYLQIFRKL WCRQIPGTSS VVQRKWKPLQ PASQPRGPGQ QTKSRISAVA AEIKQIRARR
KTARMLMVVL LVFAICYLPI SILNVLKRVF GMFTHTEDRE TVYAWFTFSH WLVYANSAAN
PIIYNFLSGK FREEFKAAFS CCCLGVHHRQ EDRLTRGRTS TESRKSLTTQ ISNFDNVSKL
SEQVVLTSIS TLPAANGAGP LQNW
