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Protein

Orexin receptor type 1

Gene

HCRTR1

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

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

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: GO_Central
  • 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
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

EuPathDBiHostDB:ENSG00000121764.11
HGNCiHGNC:4848 HCRTR1
MIMi602392 gene
neXtProtiNX_O43613

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 – 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

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...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO43613
PRIDEiO43613
ProteomicsDBi49081

PTM databases

iPTMnetiO43613
PhosphoSitePlusiO43613

Expressioni

Gene expression databases

BgeeiENSG00000121764 Expressed in 63 organ(s), highest expression level in apex of heart
CleanExiHS_HCRTR1
ExpressionAtlasiO43613 baseline and differential
GenevisibleiO43613 HS

Organism-specific databases

HPAiHPA014018

Interactioni

Protein-protein interaction databases

BioGridi109311, 2 interactors
ELMiO43613
STRINGi9606.ENSP00000362810

Chemistry databases

BindingDBiO43613

Structurei

Secondary structure

1425
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
GeneTreeiENSGT00930000150833
HOGENOMiHOG000230498
HOVERGENiHBG101173
InParanoidiO43613
KOiK04238
OMAiDEHWADD
OrthoDBiEOG091G0ZDG
PhylomeDBiO43613
TreeFamiTF315303

Family and domain databases

CDDicd15208 7tmA_OXR, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR000204 Orexin_rcpt
IPR004059 Orexin_rcpt_1
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01521 OREXIN1R
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A6NMV7A6NMV7_HUMAN
Orexin receptor type 1
HCRTR1
389Annotation score:

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 → S1 PublicationCorresponds to variant dbSNP:rs144603792Ensembl.1
Natural variantiVAR_033480279R → Q1 PublicationCorresponds to variant dbSNP:rs7516785Ensembl.1
Natural variantiVAR_044506281R → H1 PublicationCorresponds to variant dbSNP:rs41439244Ensembl.1
Natural variantiVAR_022063408I → V2 PublicationsCorresponds to variant dbSNP:rs2271933Ensembl.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

Similar proteinsi

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
ELMiO43613
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
ProteomicsDBi49081

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
EuPathDBiHostDB:ENSG00000121764.11
GeneCardsiHCRTR1
HGNCiHGNC:4848 HCRTR1
HPAiHPA014018
MIMi602392 gene
neXtProtiNX_O43613
OpenTargetsiENSG00000121764
PharmGKBiPA29222
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00930000150833
HOGENOMiHOG000230498
HOVERGENiHBG101173
InParanoidiO43613
KOiK04238
OMAiDEHWADD
OrthoDBiEOG091G0ZDG
PhylomeDBiO43613
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
SIGNORiO43613

Miscellaneous databases

ChiTaRSiHCRTR1 human
GeneWikiiHypocretin_(orexin)_receptor_1
GenomeRNAii3061
PROiPR:O43613
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121764 Expressed in 63 organ(s), highest expression level in apex of heart
CleanExiHS_HCRTR1
ExpressionAtlasiO43613 baseline and differential
GenevisibleiO43613 HS

Family and domain databases

CDDicd15208 7tmA_OXR, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR000204 Orexin_rcpt
IPR004059 Orexin_rcpt_1
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01521 OREXIN1R
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 nameiOX1R_HUMAN
AccessioniPrimary (citable) accession number: O43613
Secondary accession number(s): A8K3A6, Q9HBV6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 22, 2008
Last modified: November 7, 2018
This is version 154 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 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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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