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Protein

Orexin receptor type 2

Gene

HCRTR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides (PubMed:9491897, PubMed:26950369). Triggers an increase in cytoplasmic Ca2+ levels in response to orexin-A binding (PubMed:9491897, PubMed:26950369).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei44Important for responses to orexin1 Publication1
Binding sitei324Agonist1 Publication1

GO - Molecular functioni

  • neuropeptide receptor activity Source: ProtInc
  • orexin receptor activity Source: UniProtKB
  • peptide binding Source: GO_Central
  • peptide hormone binding Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137252-MONOMER.
ReactomeiR-HSA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiO43614.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:4849. HCRTR2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 54Extracellular1 Publication1 PublicationAdd BLAST54
Transmembranei55 – 75Helical; Name=11 PublicationAdd BLAST21
Topological domaini76 – 88Cytoplasmic1 PublicationAdd BLAST13
Transmembranei89 – 110Helical; Name=21 PublicationAdd BLAST22
Topological domaini111 – 127Extracellular1 PublicationAdd BLAST17
Transmembranei128 – 150Helical; Name=31 PublicationAdd BLAST23
Topological domaini151 – 170Cytoplasmic1 PublicationAdd BLAST20
Transmembranei171 – 191Helical; Name=41 PublicationAdd BLAST21
Topological domaini192 – 222Extracellular1 PublicationAdd BLAST31
Transmembranei223 – 243Helical; Name=51 PublicationAdd BLAST21
Topological domaini244 – 304Cytoplasmic1 PublicationAdd BLAST61
Transmembranei305 – 326Helical; Name=61 PublicationAdd BLAST22
Topological domaini327 – 342Extracellular1 PublicationAdd BLAST16
Transmembranei343 – 366Helical; Name=71 PublicationAdd BLAST24
Topological domaini367 – 444Cytoplasmic1 PublicationAdd BLAST78

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi33 – 49Missing : Abolishes response to orexin-A. 1 PublicationAdd BLAST17
Mutagenesisi44W → N: Abolishes response to orexin-A. 1 Publication1
Mutagenesisi324N → A: Strongly impairs response to orexin-A. 1 Publication1

Organism-specific databases

DisGeNETi3062.
OpenTargetsiENSG00000137252.
PharmGKBiPA29223.

Chemistry databases

ChEMBLiCHEMBL4792.
DrugBankiDB09034. Suvorexant.
GuidetoPHARMACOLOGYi322.

Polymorphism and mutation databases

BioMutaiHCRTR2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000699891 – 444Orexin receptor type 2Add BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi14N-linked (GlcNAc...)Sequence analysis1
Glycosylationi22N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi127 ↔ 210Combined sources
Glycosylationi202N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO43614.
PaxDbiO43614.
PeptideAtlasiO43614.
PRIDEiO43614.

PTM databases

iPTMnetiO43614.
PhosphoSitePlusiO43614.

Expressioni

Gene expression databases

BgeeiENSG00000137252.
CleanExiHS_HCRTR2.
ExpressionAtlasiO43614. baseline and differential.
GenevisibleiO43614. HS.

Organism-specific databases

HPAiHPA054516.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000359899.

Chemistry databases

BindingDBiO43614.

Structurei

Secondary structure

1444
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi54 – 81Combined sources28
Helixi83 – 85Combined sources3
Helixi88 – 106Combined sources19
Helixi108 – 117Combined sources10
Helixi124 – 156Combined sources33
Helixi166 – 183Combined sources18
Helixi185 – 190Combined sources6
Beta strandi191 – 196Combined sources6
Beta strandi207 – 212Combined sources6
Beta strandi215 – 217Combined sources3
Helixi218 – 231Combined sources14
Helixi233 – 251Combined sources19
Helixi294 – 328Combined sources35
Helixi340 – 367Combined sources28
Helixi369 – 378Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4S0VX-ray2.50A3-254[»]
A294-388[»]
ProteinModelPortaliO43614.
SMRiO43614.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni33 – 49Required for response to orexin-A1 PublicationAdd BLAST17

Domaini

The N-terminal region is required for orexin signaling.1 Publication

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.
InParanoidiO43614.
KOiK04239.
OMAiNSIVVIW.
OrthoDBiEOG091G0ZDG.
PhylomeDBiO43614.
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.

O43614-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGTKLEDSP PCRNWSSASE LNETQEPFLN PTDYDDEEFL RYLWREYLHP
60 70 80 90 100
KEYEWVLIAG YIIVFVVALI GNVLVCVAVW KNHHMRTVTN YFIVNLSLAD
110 120 130 140 150
VLVTITCLPA TLVVDITETW FFGQSLCKVI PYLQTVSVSV SVLTLSCIAL
160 170 180 190 200
DRWYAICHPL MFKSTAKRAR NSIVIIWIVS CIIMIPQAIV MECSTVFPGL
210 220 230 240 250
ANKTTLFTVC DERWGGEIYP KMYHICFFLV TYMAPLCLMV LAYLQIFRKL
260 270 280 290 300
WCRQIPGTSS VVQRKWKPLQ PVSQPRGPGQ PTKSRMSAVA AEIKQIRARR
310 320 330 340 350
KTARMLMIVL LVFAICYLPI SILNVLKRVF GMFAHTEDRE TVYAWFTFSH
360 370 380 390 400
WLVYANSAAN PIIYNFLSGK FREEFKAAFS CCCLGVHHRQ EDRLTRGRTS
410 420 430 440
TESRKSLTTQ ISNFDNISKL SEQVVLTSIS TLPAANGAGP LQNW
Length:444
Mass (Da):50,694
Last modified:September 23, 2008 - v2
Checksum:iC4C9A153D42254C6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04450710P → S.1 PublicationCorresponds to variant rs41271310dbSNPEnsembl.1
Natural variantiVAR_04450811P → T.1 PublicationCorresponds to variant rs41271312dbSNPEnsembl.1
Natural variantiVAR_044509293I → V.1 PublicationCorresponds to variant rs74720027dbSNPEnsembl.1
Natural variantiVAR_044510308I → V.2 PublicationsCorresponds to variant rs2653349dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041245 mRNA. Translation: AAC39602.1.
AY062031 Genomic DNA. Translation: AAL47215.1.
AL591718, AL449104 Genomic DNA. Translation: CAH73407.1.
AL449104, AL591718 Genomic DNA. Translation: CAI19665.1.
CH471081 Genomic DNA. Translation: EAX04440.1.
CCDSiCCDS4956.1.
RefSeqiNP_001517.2. NM_001526.3.
UniGeneiHs.151624.
Hs.699147.

Genome annotation databases

EnsembliENST00000370862; ENSP00000359899; ENSG00000137252.
ENST00000615358; ENSP00000477548; ENSG00000137252.
GeneIDi3062.
KEGGihsa:3062.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041245 mRNA. Translation: AAC39602.1.
AY062031 Genomic DNA. Translation: AAL47215.1.
AL591718, AL449104 Genomic DNA. Translation: CAH73407.1.
AL449104, AL591718 Genomic DNA. Translation: CAI19665.1.
CH471081 Genomic DNA. Translation: EAX04440.1.
CCDSiCCDS4956.1.
RefSeqiNP_001517.2. NM_001526.3.
UniGeneiHs.151624.
Hs.699147.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4S0VX-ray2.50A3-254[»]
A294-388[»]
ProteinModelPortaliO43614.
SMRiO43614.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000359899.

Chemistry databases

BindingDBiO43614.
ChEMBLiCHEMBL4792.
DrugBankiDB09034. Suvorexant.
GuidetoPHARMACOLOGYi322.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO43614.
PhosphoSitePlusiO43614.

Polymorphism and mutation databases

BioMutaiHCRTR2.

Proteomic databases

EPDiO43614.
PaxDbiO43614.
PeptideAtlasiO43614.
PRIDEiO43614.

Protocols and materials databases

DNASUi3062.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370862; ENSP00000359899; ENSG00000137252.
ENST00000615358; ENSP00000477548; ENSG00000137252.
GeneIDi3062.
KEGGihsa:3062.

Organism-specific databases

CTDi3062.
DisGeNETi3062.
GeneCardsiHCRTR2.
HGNCiHGNC:4849. HCRTR2.
HPAiHPA054516.
MIMi602393. gene.
neXtProtiNX_O43614.
OpenTargetsiENSG00000137252.
PharmGKBiPA29223.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000230498.
HOVERGENiHBG101173.
InParanoidiO43614.
KOiK04239.
OMAiNSIVVIW.
OrthoDBiEOG091G0ZDG.
PhylomeDBiO43614.
TreeFamiTF315303.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137252-MONOMER.
ReactomeiR-HSA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiO43614.

Miscellaneous databases

GeneWikiiHypocretin_(orexin)_receptor_2.
GenomeRNAii3062.
PROiO43614.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137252.
CleanExiHS_HCRTR2.
ExpressionAtlasiO43614. baseline and differential.
GenevisibleiO43614. HS.

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...

Entry informationi

Entry nameiOX2R_HUMAN
AccessioniPrimary (citable) accession number: O43614
Secondary accession number(s): Q5VTM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 23, 2008
Last modified: November 2, 2016
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. 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.