ID OX1R_HUMAN Reviewed; 425 AA. AC O43613; A8K3A6; Q9HBV6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 2. DT 27-MAR-2024, entry version 185. DE RecName: Full=Orexin/Hypocretin receptor type 1 {ECO:0000305|PubMed:11723285}; DE AltName: Full=Hypocretin receptor type 1 {ECO:0000312|HGNC:HGNC:4848}; DE AltName: Full=Orexin receptor type 1 {ECO:0000305|PubMed:9491897}; DE Short=Ox-1-R; DE Short=Ox1-R; DE Short=Ox1R; GN Name=HCRTR1 {ECO:0000312|HGNC:HGNC:4848}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=9491897; DOI=10.1016/s0092-8674(00)80949-6; RA Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R.M., Tanaka H., RA Williams S.C., Richardson J.A., Kozlowski G.P., Wilson S., Arch J.R.S., RA Buckingham R.E., Haynes A.C., Carr S.A., Annan R.S., McNulty D.E., RA Liu W.-S., Terrett J.A., Elshourbagy N.A., Bergsma D.J., Yanagisawa M.; RT "Orexins and orexin receptors: a family of hypothalamic neuropeptides and G RT protein-coupled receptors that regulate feeding behavior."; RL Cell 92:573-585(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10973318; DOI=10.1038/79690; RA Peyron C., Faraco J., Rogers W., Ripley B., Overeem S., Charnay Y., RA Nevsimalova S., Aldrich M., Reynolds D., Albin R., Li R., Hungs M., RA Pedrazzoli M., Padigaru M., Kucherlapati M., Fan J., Maki R., Lammers G.J., RA Bouras C., Kucherlapati R., Nishino S., Mignot E.; RT "A mutation in a case of early onset narcolepsy and a generalized absence RT of hypocretin peptides in human narcoleptic brains."; RL Nat. Med. 6:991-997(2000). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-167; GLN-279; HIS-281 RP AND VAL-408. RX PubMed=11723285; DOI=10.1212/wnl.57.10.1896; RA Olafsdottir B.R., Rye D.B., Scammell T.E., Matheson J.K., Stefansson K., RA Gulcher J.R.; RT "Polymorphisms in hypocretin/orexin pathway genes and narcolepsy."; RL Neurology 57:1896-1899(2001). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Yeager M., Welch R., Haque K., Bergen A.; RT "Genomic sequence of the hypocretin (orexin) receptor 1 (HCRTR1)."; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-408. RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] 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 [10] 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 [11] {ECO:0007744|PDB:4ZJ8, ECO:0007744|PDB:4ZJC} RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 1-246 AND 288-380 IN COMPLEXES RP WITH THE ANTAGONISTS SUVOREXANT AND SB-674042, DISULFIDE BONDS, FUNCTION, RP SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF 26-ASP--TYR-41; TRP-36 AND RP ASN-318, AND DOMAIN. RX PubMed=26950369; DOI=10.1038/nsmb.3183; RA Yin J., Babaoglu K., Brautigam C.A., Clark L., Shao Z., Scheuermann T.H., RA Harrell C.M., Gotter A.L., Roecker A.J., Winrow C.J., Renger J.J., RA Coleman P.J., Rosenbaum D.M.; RT "Structure and ligand-binding mechanism of the human OX1 and OX2 orexin RT receptors."; RL Nat. Struct. Mol. Biol. 23:293-299(2016). CC -!- FUNCTION: Moderately selective excitatory receptor for orexin-A and, CC with a lower affinity, for orexin-B neuropeptide (PubMed:9491897, CC PubMed:26950369). Triggers an increase in cytoplasmic Ca(2+) levels in CC response to orexin-A binding (PubMed:9491897, PubMed:26950369). CC {ECO:0000269|PubMed:26950369, ECO:0000269|PubMed:9491897}. CC -!- INTERACTION: CC O43613; P35414: APLNR; NbExp=6; IntAct=EBI-21914411, EBI-2875891; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26950369, CC ECO:0000269|PubMed:9491897}; Multi-pass membrane protein CC {ECO:0000269|PubMed:26950369}. CC -!- DOMAIN: The N-terminal region is required for orexin signaling. CC {ECO:0000269|PubMed:26950369}. CC -!- MISCELLANEOUS: The antagonists suvorexant and SB-674042 bind at the CC cognate neuropeptide binding site that is situated between the CC transmembrane helices and accessible from the extracellular side of the CC membrane. {ECO:0000269|PubMed:26950369}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF041243; AAC39601.1; -; mRNA. DR EMBL; AF202084; AAG28020.1; -; Genomic_DNA. DR EMBL; AF202078; AAG28020.1; JOINED; Genomic_DNA. DR EMBL; AF202079; AAG28020.1; JOINED; Genomic_DNA. DR EMBL; AF202080; AAG28020.1; JOINED; Genomic_DNA. DR EMBL; AF202081; AAG28020.1; JOINED; Genomic_DNA. DR EMBL; AF202082; AAG28020.1; JOINED; Genomic_DNA. DR EMBL; AF202083; AAG28020.1; JOINED; Genomic_DNA. DR EMBL; AY062030; AAL47214.1; -; Genomic_DNA. DR EMBL; AY070269; AAL50221.1; -; Genomic_DNA. DR EMBL; AK290521; BAF83210.1; -; mRNA. DR EMBL; AC114488; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07602.1; -; Genomic_DNA. DR EMBL; BC074796; AAH74796.1; -; mRNA. DR CCDS; CCDS344.1; -. DR RefSeq; NP_001516.2; NM_001525.2. DR RefSeq; XP_016856594.1; XM_017001105.1. DR RefSeq; XP_016856595.1; XM_017001106.1. DR PDB; 4ZJ8; X-ray; 2.75 A; A=1-246, A=288-380. DR PDB; 4ZJC; X-ray; 2.83 A; A=1-246, A=288-380. DR PDB; 6TO7; X-ray; 2.26 A; A/B=28-380. DR PDB; 6TOD; X-ray; 2.11 A; A/B=28-380. DR PDB; 6TOS; X-ray; 2.13 A; A/B=28-380. DR PDB; 6TOT; X-ray; 2.22 A; A/B=28-380. DR PDB; 6TP3; X-ray; 3.04 A; A/B=28-380. DR PDB; 6TP4; X-ray; 3.01 A; A/B=28-380. DR PDB; 6TP6; X-ray; 2.34 A; A/B=28-380. DR PDB; 6TQ4; X-ray; 2.30 A; A/B=28-380. DR PDB; 6TQ6; X-ray; 2.55 A; A/B=28-380. DR PDB; 6TQ7; X-ray; 2.66 A; A/B=28-380. DR PDB; 6TQ9; X-ray; 2.65 A; A/B=28-381. DR PDB; 6V9S; X-ray; 3.50 A; A=1-246, A=288-380. DR PDBsum; 4ZJ8; -. DR PDBsum; 4ZJC; -. DR PDBsum; 6TO7; -. DR PDBsum; 6TOD; -. DR PDBsum; 6TOS; -. DR PDBsum; 6TOT; -. DR PDBsum; 6TP3; -. DR PDBsum; 6TP4; -. DR PDBsum; 6TP6; -. DR PDBsum; 6TQ4; -. DR PDBsum; 6TQ6; -. DR PDBsum; 6TQ7; -. DR PDBsum; 6TQ9; -. DR PDBsum; 6V9S; -. DR AlphaFoldDB; O43613; -. DR SMR; O43613; -. DR BioGRID; 109311; 6. DR ELM; O43613; -. DR IntAct; O43613; 4. DR MINT; O43613; -. DR STRING; 9606.ENSP00000384387; -. DR BindingDB; O43613; -. DR ChEMBL; CHEMBL5113; -. DR DrugBank; DB15031; Daridorexant. DR DrugBank; DB11951; Lemborexant. DR DrugBank; DB09034; Suvorexant. DR DrugCentral; O43613; -. DR GuidetoPHARMACOLOGY; 321; -. DR GlyCosmos; O43613; 3 sites, 1 glycan. DR GlyGen; O43613; 3 sites, 1 O-linked glycan (2 sites). DR iPTMnet; O43613; -. DR PhosphoSitePlus; O43613; -. DR BioMuta; HCRTR1; -. DR MassIVE; O43613; -. DR PaxDb; 9606-ENSP00000384387; -. DR ProteomicsDB; 49081; -. DR Antibodypedia; 2934; 467 antibodies from 39 providers. DR DNASU; 3061; -. DR Ensembl; ENST00000373706.9; ENSP00000362810.5; ENSG00000121764.12. DR Ensembl; ENST00000403528.7; ENSP00000384387.2; ENSG00000121764.12. DR GeneID; 3061; -. DR KEGG; hsa:3061; -. DR MANE-Select; ENST00000403528.7; ENSP00000384387.2; NM_001525.3; NP_001516.2. DR UCSC; uc001btd.3; human. DR AGR; HGNC:4848; -. DR CTD; 3061; -. DR DisGeNET; 3061; -. DR GeneCards; HCRTR1; -. DR HGNC; HGNC:4848; HCRTR1. DR HPA; ENSG00000121764; Tissue enhanced (adrenal). DR MIM; 602392; gene. DR neXtProt; NX_O43613; -. DR OpenTargets; ENSG00000121764; -. DR PharmGKB; PA29222; -. DR VEuPathDB; HostDB:ENSG00000121764; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01070000253744; -. DR HOGENOM; CLU_009579_6_3_1; -. DR InParanoid; O43613; -. DR OMA; HTLCKVI; -. DR OrthoDB; 2949325at2759; -. DR PhylomeDB; O43613; -. DR TreeFam; TF315303; -. DR PathwayCommons; O43613; -. DR Reactome; R-HSA-389397; Orexin and neuropeptides FF and QRFP bind to their respective receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; O43613; -. DR SIGNOR; O43613; -. DR BioGRID-ORCS; 3061; 153 hits in 1144 CRISPR screens. DR ChiTaRS; HCRTR1; human. DR GeneWiki; Hypocretin_(orexin)_receptor_1; -. DR GenomeRNAi; 3061; -. DR Pharos; O43613; Tclin. DR PRO; PR:O43613; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O43613; Protein. DR Bgee; ENSG00000121764; Expressed in apex of heart and 99 other cell types or tissues. DR ExpressionAtlas; O43613; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc. DR GO; GO:0016499; F:orexin receptor activity; IDA:UniProtKB. DR GO; GO:0042277; F:peptide binding; IBA:GO_Central. DR GO; GO:0017046; F:peptide hormone binding; IEA:Ensembl. DR GO; GO:0032870; P:cellular response to hormone stimulus; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0007631; P:feeding behavior; TAS:ProtInc. DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IDA:UniProtKB. DR CDD; cd15208; 7tmA_OXR; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR000204; Orexin_rcpt. DR InterPro; IPR004059; OX1R. DR PANTHER; PTHR45695:SF24; G_PROTEIN_RECEP_F1_2 DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR45695; LEUCOKININ RECEPTOR-RELATED; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR01521; OREXIN1R. DR PRINTS; PR01064; OREXINR. DR SMART; SM01381; 7TM_GPCR_Srsx; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; O43613; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor; KW Glycoprotein; Membrane; Receptor; Reference proteome; Transducer; KW Transmembrane; Transmembrane helix. FT CHAIN 1..425 FT /note="Orexin/Hypocretin receptor type 1" FT /id="PRO_0000069984" FT TOPO_DOM 1..46 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 47..67 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 68..82 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 83..105 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 106..119 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 120..140 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 141..160 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 161..182 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 183..213 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 214..235 FT /note="Helical; Name=5" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 236..298 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 299..321 FT /note="Helical; Name=6" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 322..336 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:26950369" FT TRANSMEM 337..360 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:26950369" FT TOPO_DOM 361..425 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26950369" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 26..41 FT /note="Required for response to orexin-A" FT /evidence="ECO:0000269|PubMed:26950369" FT BINDING 318 FT /ligand="suvorexant" FT /ligand_id="ChEBI:CHEBI:82698" FT /ligand_note="antagonist" FT /evidence="ECO:0000269|PubMed:26950369, FT ECO:0007744|PDB:4ZJ8" FT SITE 36 FT /note="Important for responses to orexin" FT /evidence="ECO:0000269|PubMed:26950369" FT CARBOHYD 194 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 119..202 FT /evidence="ECO:0007744|PDB:4ZJ8, ECO:0007744|PDB:4ZJC" FT VARIANT 167 FT /note="G -> S (in dbSNP:rs144603792)" FT /evidence="ECO:0000269|PubMed:11723285" FT /id="VAR_044505" FT VARIANT 279 FT /note="R -> Q (in dbSNP:rs7516785)" FT /evidence="ECO:0000269|PubMed:11723285" FT /id="VAR_033480" FT VARIANT 281 FT /note="R -> H (in dbSNP:rs41439244)" FT /evidence="ECO:0000269|PubMed:11723285" FT /id="VAR_044506" FT VARIANT 408 FT /note="I -> V (in dbSNP:rs2271933)" FT /evidence="ECO:0000269|PubMed:11723285, FT ECO:0000269|PubMed:14702039" FT /id="VAR_022063" FT MUTAGEN 26..41 FT /note="Missing: Abolishes response to orexin-A." FT /evidence="ECO:0000269|PubMed:26950369" FT MUTAGEN 36 FT /note="W->A: Strongly impairs response to orexin-A." FT /evidence="ECO:0000269|PubMed:26950369" FT MUTAGEN 318 FT /note="N->A: Strongly impairs response to orexin-A." FT /evidence="ECO:0000269|PubMed:26950369" FT CONFLICT 280 FT /note="A -> G (in Ref. 1; AAC39601)" FT /evidence="ECO:0000305" FT HELIX 30..38 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 40..43 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 46..73 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 75..77 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 80..109 FT /evidence="ECO:0007829|PDB:6TOD" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:6TP6" FT HELIX 115..149 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 151..153 FT /evidence="ECO:0007829|PDB:4ZJ8" FT HELIX 158..175 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 177..182 FT /evidence="ECO:0007829|PDB:6TOD" FT STRAND 183..189 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:6TOD" FT TURN 193..195 FT /evidence="ECO:0007829|PDB:6TOD" FT STRAND 200..204 FT /evidence="ECO:0007829|PDB:6TOD" FT STRAND 207..210 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 211..223 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 225..242 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 287..322 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 333..361 FT /evidence="ECO:0007829|PDB:6TOD" FT HELIX 363..374 FT /evidence="ECO:0007829|PDB:6TOD" SQ SEQUENCE 425 AA; 47536 MW; B650B37F3A2CA096 CRC64; MEPSATPGAQ MGVPPGSREP SPVPPDYEDE FLRYLWRDYL YPKQYEWVLI AAYVAVFVVA LVGNTLVCLA VWRNHHMRTV TNYFIVNLSL ADVLVTAICL PASLLVDITE SWLFGHALCK VIPYLQAVSV SVAVLTLSFI ALDRWYAICH PLLFKSTARR ARGSILGIWA VSLAIMVPQA AVMECSSVLP ELANRTRLFS VCDERWADDL YPKIYHSCFF IVTYLAPLGL MAMAYFQIFR KLWGRQIPGT TSALVRNWKR PSDQLGDLEQ GLSGEPQPRA RAFLAEVKQM RARRKTAKML MVVLLVFALC YLPISVLNVL KRVFGMFRQA SDREAVYACF TFSHWLVYAN SAANPIIYNF LSGKFREQFK AAFSCCLPGL GPCGSLKAPS PRSSASHKSL SLQSRCSISK ISEHVVLTSV TTVLP //