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Protein

Orexin receptor type 2

Gene

HCRTR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • G protein-coupled receptor activity Source: GO_Central
  • neuropeptide receptor activity Source: ProtInc
  • orexin receptor activity Source: UniProtKB
  • peptide hormone binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000137252.9
HGNCiHGNC:4849 HCRTR2
MIMi602393 gene
neXtProtiNX_O43614

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Glycosylationi22N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi127 ↔ 210Combined sources
Glycosylationi202N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiO43614
PaxDbiO43614
PeptideAtlasiO43614
PRIDEiO43614
ProteomicsDBi49082

PTM databases

iPTMnetiO43614
PhosphoSitePlusiO43614

Expressioni

Gene expression databases

BgeeiENSG00000137252 Expressed in 32 organ(s), highest expression level in frontal cortex
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

3D structure databases

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
GeneTreeiENSGT00930000150833
HOGENOMiHOG000230498
HOVERGENiHBG101173
InParanoidiO43614
KOiK04239
OMAiHWLIYAN
OrthoDBiEOG091G0ZDG
PhylomeDBiO43614
TreeFamiTF315303

Family and domain databases

CDDicd15208 7tmA_OXR, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR000204 Orexin_rcpt
IPR004060 Orexin_rcpt_2
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PF03827 Orexin_rec2, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01522 OREXIN2R
PR01064 OREXINR
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 → S1 PublicationCorresponds to variant dbSNP:rs41271310Ensembl.1
Natural variantiVAR_04450811P → T1 PublicationCorresponds to variant dbSNP:rs41271312Ensembl.1
Natural variantiVAR_044509293I → V1 PublicationCorresponds to variant dbSNP:rs74720027Ensembl.1
Natural variantiVAR_044510308I → V2 PublicationsCorresponds to variant dbSNP:rs2653349Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041245 mRNA Translation: AAC39602.1
AY062031 Genomic DNA Translation: AAL47215.1
AL591718 Genomic DNA No translation available.
AL449104 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04440.1
CCDSiCCDS4956.1
RefSeqiNP_001517.2, NM_001526.4
UniGeneiHs.151624
Hs.699147

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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 Genomic DNA No translation available.
AL449104 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04440.1
CCDSiCCDS4956.1
RefSeqiNP_001517.2, NM_001526.4
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[»]
5WQCX-ray1.96A3-254[»]
A294-386[»]
5WS3X-ray2.30A3-254[»]
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
ProteomicsDBi49082

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
EuPathDBiHostDB:ENSG00000137252.9
GeneCardsiHCRTR2
HGNCiHGNC:4849 HCRTR2
HPAiHPA054516
MIMi602393 gene
neXtProtiNX_O43614
OpenTargetsiENSG00000137252
PharmGKBiPA29223
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00930000150833
HOGENOMiHOG000230498
HOVERGENiHBG101173
InParanoidiO43614
KOiK04239
OMAiHWLIYAN
OrthoDBiEOG091G0ZDG
PhylomeDBiO43614
TreeFamiTF315303

Enzyme and pathway databases

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

ChiTaRSiHCRTR2 human
GeneWikiiHypocretin_(orexin)_receptor_2
GenomeRNAii3062
PROiPR:O43614
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137252 Expressed in 32 organ(s), highest expression level in frontal cortex
CleanExiHS_HCRTR2
ExpressionAtlasiO43614 baseline and differential
GenevisibleiO43614 HS

Family and domain databases

CDDicd15208 7tmA_OXR, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR000204 Orexin_rcpt
IPR004060 Orexin_rcpt_2
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PF03827 Orexin_rec2, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01522 OREXIN2R
PR01064 OREXINR
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiOX2R_HUMAN
AccessioniPrimary (citable) accession number: O43614
Secondary accession number(s): Q5VTM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 23, 2008
Last modified: November 7, 2018
This is version 149 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  7. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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