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Protein

Orexin receptor type 1

Gene

HCRTR1

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

Functioni

Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide (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
Sitei36Important for responses to orexin1 Publication1
Binding sitei318AgonistCombined sources1 Publication1

GO - Molecular functioni

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

GO - Biological processi

  • cellular response to hormone stimulus Source: GO_Central
  • chemical synaptic transmission Source: ProtInc
  • feeding behavior Source: ProtInc
  • neuropeptide signaling pathway Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  • regulation of circadian sleep/wake cycle, sleep Source: GO_Central
  • regulation of cytosolic calcium ion concentration Source: UniProtKB
  • response to peptide Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121764-MONOMER.
ReactomeiR-HSA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiO43613.

Names & Taxonomyi

Protein namesi
Recommended name:
Orexin receptor type 1
Short name:
Ox-1-R
Short name:
Ox1-R
Short name:
Ox1R
Alternative name(s):
Hypocretin receptor type 1
Gene namesi
Name:HCRTR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:4848. HCRTR1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 46Extracellular1 PublicationAdd BLAST46
Transmembranei47 – 67Helical; Name=11 PublicationAdd BLAST21
Topological domaini68 – 82Cytoplasmic1 PublicationAdd BLAST15
Transmembranei83 – 105Helical; Name=21 PublicationAdd BLAST23
Topological domaini106 – 119Extracellular1 PublicationAdd BLAST14
Transmembranei120 – 140Helical; Name=31 PublicationAdd BLAST21
Topological domaini141 – 160Cytoplasmic1 PublicationAdd BLAST20
Transmembranei161 – 182Helical; Name=41 PublicationAdd BLAST22
Topological domaini183 – 213Extracellular1 PublicationAdd BLAST31
Transmembranei214 – 235Helical; Name=51 PublicationAdd BLAST22
Topological domaini236 – 298Cytoplasmic1 PublicationAdd BLAST63
Transmembranei299 – 321Helical; Name=61 PublicationAdd BLAST23
Topological domaini322 – 336Extracellular1 PublicationAdd BLAST15
Transmembranei337 – 360Helical; Name=71 PublicationAdd BLAST24
Topological domaini361 – 425Cytoplasmic1 PublicationAdd BLAST65

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
Mutagenesisi26 – 41Missing : Abolishes response to orexin-A. 1 PublicationAdd BLAST16
Mutagenesisi36W → A: Strongly impairs response to orexin-A. 1 Publication1
Mutagenesisi318N → A: Strongly impairs response to orexin-A. 1 Publication1

Organism-specific databases

DisGeNETi3061.
OpenTargetsiENSG00000121764.
PharmGKBiPA29222.

Chemistry databases

ChEMBLiCHEMBL5113.
DrugBankiDB09034. Suvorexant.
GuidetoPHARMACOLOGYi321.

Polymorphism and mutation databases

BioMutaiHCRTR1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000699841 – 425Orexin receptor type 1Add BLAST425

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi119 ↔ 202Combined sources
Glycosylationi194N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO43613.
PRIDEiO43613.

PTM databases

iPTMnetiO43613.
PhosphoSitePlusiO43613.

Expressioni

Gene expression databases

BgeeiENSG00000121764.
CleanExiHS_HCRTR1.
ExpressionAtlasiO43613. baseline and differential.
GenevisibleiO43613. HS.

Organism-specific databases

HPAiHPA014018.

Interactioni

Protein-protein interaction databases

BioGridi109311. 2 interactors.
STRINGi9606.ENSP00000362810.

Chemistry databases

BindingDBiO43613.

Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi28 – 36Combined sources9
Helixi47 – 73Combined sources27
Helixi80 – 109Combined sources30
Helixi116 – 149Combined sources34
Helixi151 – 153Combined sources3
Helixi158 – 174Combined sources17
Helixi177 – 182Combined sources6
Beta strandi183 – 186Combined sources4
Beta strandi201 – 204Combined sources4
Beta strandi207 – 209Combined sources3
Helixi210 – 223Combined sources14
Helixi225 – 242Combined sources18
Helixi288 – 322Combined sources35
Helixi334 – 361Combined sources28
Helixi363 – 371Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZJ8X-ray2.75A1-246[»]
A288-380[»]
4ZJCX-ray2.83A1-246[»]
A288-380[»]
ProteinModelPortaliO43613.
SMRiO43613.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni26 – 41Required for response to orexin-A1 PublicationAdd BLAST16

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.
InParanoidiO43613.
KOiK04238.
OMAiLMEPSAT.
OrthoDBiEOG091G0ZDG.
PhylomeDBiO43613.
TreeFamiTF315303.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000204. Orexin_rcpt.
IPR004059. Orexin_rcpt_1.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01521. OREXIN1R.
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.

O43613-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPSATPGAQ MGVPPGSREP SPVPPDYEDE FLRYLWRDYL YPKQYEWVLI
60 70 80 90 100
AAYVAVFVVA LVGNTLVCLA VWRNHHMRTV TNYFIVNLSL ADVLVTAICL
110 120 130 140 150
PASLLVDITE SWLFGHALCK VIPYLQAVSV SVAVLTLSFI ALDRWYAICH
160 170 180 190 200
PLLFKSTARR ARGSILGIWA VSLAIMVPQA AVMECSSVLP ELANRTRLFS
210 220 230 240 250
VCDERWADDL YPKIYHSCFF IVTYLAPLGL MAMAYFQIFR KLWGRQIPGT
260 270 280 290 300
TSALVRNWKR PSDQLGDLEQ GLSGEPQPRA RAFLAEVKQM RARRKTAKML
310 320 330 340 350
MVVLLVFALC YLPISVLNVL KRVFGMFRQA SDREAVYACF TFSHWLVYAN
360 370 380 390 400
SAANPIIYNF LSGKFREQFK AAFSCCLPGL GPCGSLKAPS PRSSASHKSL
410 420
SLQSRCSISK ISEHVVLTSV TTVLP
Length:425
Mass (Da):47,536
Last modified:July 22, 2008 - v2
Checksum:iB650B37F3A2CA096
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti280A → G in AAC39601 (PubMed:9491897).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_044505167G → S.1 PublicationCorresponds to variant rs144603792dbSNPEnsembl.1
Natural variantiVAR_033480279R → Q.1 PublicationCorresponds to variant rs7516785dbSNPEnsembl.1
Natural variantiVAR_044506281R → H.1 PublicationCorresponds to variant rs41439244dbSNPEnsembl.1
Natural variantiVAR_022063408I → V.2 PublicationsCorresponds to variant rs2271933dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041243 mRNA. Translation: AAC39601.1.
AF202084
, AF202078, AF202079, AF202080, AF202081, AF202082, AF202083 Genomic DNA. Translation: AAG28020.1.
AY062030 Genomic DNA. Translation: AAL47214.1.
AY070269 Genomic DNA. Translation: AAL50221.1.
AK290521 mRNA. Translation: BAF83210.1.
AC114488 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07602.1.
BC074796 mRNA. Translation: AAH74796.1.
CCDSiCCDS344.1.
RefSeqiNP_001516.2. NM_001525.2.
XP_016856594.1. XM_017001105.1.
XP_016856595.1. XM_017001106.1.
UniGeneiHs.388226.

Genome annotation databases

EnsembliENST00000373706; ENSP00000362810; ENSG00000121764.
ENST00000403528; ENSP00000384387; ENSG00000121764.
GeneIDi3061.
KEGGihsa:3061.
UCSCiuc001btd.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF041243 mRNA. Translation: AAC39601.1.
AF202084
, AF202078, AF202079, AF202080, AF202081, AF202082, AF202083 Genomic DNA. Translation: AAG28020.1.
AY062030 Genomic DNA. Translation: AAL47214.1.
AY070269 Genomic DNA. Translation: AAL50221.1.
AK290521 mRNA. Translation: BAF83210.1.
AC114488 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07602.1.
BC074796 mRNA. Translation: AAH74796.1.
CCDSiCCDS344.1.
RefSeqiNP_001516.2. NM_001525.2.
XP_016856594.1. XM_017001105.1.
XP_016856595.1. XM_017001106.1.
UniGeneiHs.388226.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZJ8X-ray2.75A1-246[»]
A288-380[»]
4ZJCX-ray2.83A1-246[»]
A288-380[»]
ProteinModelPortaliO43613.
SMRiO43613.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109311. 2 interactors.
STRINGi9606.ENSP00000362810.

Chemistry databases

BindingDBiO43613.
ChEMBLiCHEMBL5113.
DrugBankiDB09034. Suvorexant.
GuidetoPHARMACOLOGYi321.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO43613.
PhosphoSitePlusiO43613.

Polymorphism and mutation databases

BioMutaiHCRTR1.

Proteomic databases

PaxDbiO43613.
PRIDEiO43613.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373706; ENSP00000362810; ENSG00000121764.
ENST00000403528; ENSP00000384387; ENSG00000121764.
GeneIDi3061.
KEGGihsa:3061.
UCSCiuc001btd.3. human.

Organism-specific databases

CTDi3061.
DisGeNETi3061.
GeneCardsiHCRTR1.
HGNCiHGNC:4848. HCRTR1.
HPAiHPA014018.
MIMi602392. gene.
neXtProtiNX_O43613.
OpenTargetsiENSG00000121764.
PharmGKBiPA29222.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000230498.
HOVERGENiHBG101173.
InParanoidiO43613.
KOiK04238.
OMAiLMEPSAT.
OrthoDBiEOG091G0ZDG.
PhylomeDBiO43613.
TreeFamiTF315303.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121764-MONOMER.
ReactomeiR-HSA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiO43613.

Miscellaneous databases

ChiTaRSiHCRTR1. human.
GeneWikiiHypocretin_(orexin)_receptor_1.
GenomeRNAii3061.
PROiO43613.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121764.
CleanExiHS_HCRTR1.
ExpressionAtlasiO43613. baseline and differential.
GenevisibleiO43613. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000204. Orexin_rcpt.
IPR004059. Orexin_rcpt_1.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01521. OREXIN1R.
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 nameiOX1R_HUMAN
AccessioniPrimary (citable) accession number: O43613
Secondary accession number(s): A8K3A6, Q9HBV6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 22, 2008
Last modified: November 2, 2016
This is version 139 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

Miscellaneous

The antagonists suvorexant and SB-674042 bind at the cognate neuropeptide binding site that is situated between the transmembrane helices and accessible from the extracellular side of the membrane.1 Publication

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 1
    Human chromosome 1: 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.