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Protein

Orexin receptor type 2

Gene

HCRTR2

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-CFA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-CFA-416476. G alpha (q) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Orexin receptor type 2
Short name:
Ox-2-R
Short name:
Ox2-R
Short name:
Ox2R
Alternative name(s):
Hypocretin receptor type 2
Gene namesi
Name:HCRTR2
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 12

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 5454ExtracellularSequence analysisAdd
BLAST
Transmembranei55 – 7521Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini76 – 8813CytoplasmicSequence analysisAdd
BLAST
Transmembranei89 – 11022Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini111 – 12717ExtracellularSequence analysisAdd
BLAST
Transmembranei128 – 15023Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini151 – 17222CytoplasmicSequence analysisAdd
BLAST
Transmembranei173 – 19321Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini194 – 22431ExtracellularSequence analysisAdd
BLAST
Transmembranei225 – 24723Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini248 – 30457CytoplasmicSequence analysisAdd
BLAST
Transmembranei305 – 32723Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini328 – 34215ExtracellularSequence analysisAdd
BLAST
Transmembranei343 – 36624Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini367 – 44478CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in HCRTR2 are a cause of an autosomal recessive form of narcolepsy, observed in labradors, dobermans and dachshunds. Narcolepsy is a neurological sleep disorder affecting animals and humans, characterized by excessive daytime sleepiness, sleep fragmentation, symptoms of abnormal rapid-eye-movement (REM) sleep, such as cataplexy, hypnagogic hallucinations, and sleep paralysis. Cataplexy is a sudden loss of muscle tone triggered by emotions, which is the most valuable clinical feature used to diagnose narcolepsy. As in humans, most cases of canine narcolepsy are sporadic but an autosomal recessive form was also observed.

Keywords - Diseasei

Disease mutation

Chemistry

ChEMBLiCHEMBL3337331.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444Orexin receptor type 2PRO_0000069988Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi14 – 141N-linked (GlcNAc...)Sequence analysis
Glycosylationi22 – 221N-linked (GlcNAc...)Sequence analysis
Glycosylationi202 – 2021N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9TUP7.

Interactioni

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000003376.

Structurei

3D structure databases

ProteinModelPortaliQ9TUP7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000230498.
HOVERGENiHBG101173.
InParanoidiQ9TUP7.
KOiK04239.
OMAiNSIVVIW.
OrthoDBiEOG7CG72H.
TreeFamiTF315303.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000204. Orexin_rcpt.
IPR004060. Orexin_rcpt_2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
PF03827. Orexin_rec2. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01522. OREXIN2R.
PR01064. OREXINR.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9TUP7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGTKLEDSP PCRNWSSAPE LNETQEPFLN PTDYDDEEFL RYLWREYLHP
60 70 80 90 100
KEYEWVLIAG YIIVFVVALV GNVLVCVAVW KNHHMRTVTN YFIVNLSLAD
110 120 130 140 150
VLVTITCLPA TLVVDITETW FFGQSLCKVI PYLQTVSVSV SVLTLSCIAL
160 170 180 190 200
DRWYAICHPL MFKSTAKRAR NSIVIIWIVS CIIMIPQAIV MECSTMLPGL
210 220 230 240 250
ANKTTLFTVC DERWGGEIYP KMYHICFFLV TYMAPLCLMV LAYLQIFRKL
260 270 280 290 300
WCRQIPGTSS VVQRKWKPLQ PASQPRGPGQ QTKSRISAVA AEIKQIRARR
310 320 330 340 350
KTARMLMVVL LVFAICYLPI SILNVLKRVF GMFTHTEDRE TVYAWFTFSH
360 370 380 390 400
WLVYANSAAN PIIYNFLSGK FREEFKAAFS CCCLGVHHRQ EDRLTRGRTS
410 420 430 440
TESRKSLTTQ ISNFDNVSKL SEQVVLTSIS TLPAANGAGP LQNW
Length:444
Mass (Da):50,675
Last modified:May 1, 2000 - v1
Checksum:iD848A4536D485D6B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti54 – 541E → K in narcolepsy; autosomal recessive; loss of function. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF164626 mRNA. Translation: AAD49333.1.
RefSeqiNP_001002933.1. NM_001002933.1.
UniGeneiCfa.3650.

Genome annotation databases

EnsembliENSCAFT00000003647; ENSCAFP00000003376; ENSCAFG00000002328.
GeneIDi399545.
KEGGicfa:399545.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF164626 mRNA. Translation: AAD49333.1.
RefSeqiNP_001002933.1. NM_001002933.1.
UniGeneiCfa.3650.

3D structure databases

ProteinModelPortaliQ9TUP7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000003376.

Chemistry

ChEMBLiCHEMBL3337331.

Protein family/group databases

GPCRDBiSearch...

Proteomic databases

PaxDbiQ9TUP7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCAFT00000003647; ENSCAFP00000003376; ENSCAFG00000002328.
GeneIDi399545.
KEGGicfa:399545.

Organism-specific databases

CTDi3062.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000230498.
HOVERGENiHBG101173.
InParanoidiQ9TUP7.
KOiK04239.
OMAiNSIVVIW.
OrthoDBiEOG7CG72H.
TreeFamiTF315303.

Enzyme and pathway databases

ReactomeiR-CFA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-CFA-416476. G alpha (q) signalling events.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000204. Orexin_rcpt.
IPR004060. Orexin_rcpt_2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
PF03827. Orexin_rec2. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01522. OREXIN2R.
PR01064. OREXINR.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin receptor 2 gene."
    Lin L., Faraco J., Li R., Kadotani H., Rogers W., Lin X., Qiu X., de Jong P.J., Nishino S., Mignot E.
    Cell 98:365-376(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Hypocretin/orexin, sleep and narcolepsy."
    Hungs M., Mignot E.
    Bioessays 23:397-408(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  3. "To eat or to sleep? Orexin in the regulation of feeding and wakefulness."
    Willie J.T., Chemelli R.M., Sinton C.M., Yanagisawa M.
    Annu. Rev. Neurosci. 24:429-458(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  4. "Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines."
    Hungs M., Fan J., Lin L., Lin X., Maki R.A., Mignot E.
    Genome Res. 11:531-539(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT NARCOLEPSY LYS-54, CHARACTERIZATION OF VARIANT LYS-54.

Entry informationi

Entry nameiOX2R_CANLF
AccessioniPrimary (citable) accession number: Q9TUP7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.