HCRTR2 (hypocretin receptor 2)

Gene

• Entrez ID: 3062
• Gene name: Hypocretin receptor 2
• Gene symbol: HCRTR2
• Synonyms (NCBI Gene): ORXR2, OX2R, OXR2
• Chromosome: 6
• Chromosome location: 6p12.1
• Summary: The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor t

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004930	Function	G protein-coupled receptor activity	IEA
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005654	Component	Nucleoplasm	IDA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	26950369
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	9491897
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IEA
GO:0007200	Process	Phospholipase C-activating G protein-coupled receptor signaling pathway	IEA
GO:0007218	Process	Neuropeptide signaling pathway	IBA
GO:0007218	Process	Neuropeptide signaling pathway	IDA	26950369
GO:0007218	Process	Neuropeptide signaling pathway	IEA
GO:0007218	Process	Neuropeptide signaling pathway	TAS	9491897
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0007268	Process	Chemical synaptic transmission	TAS	9491897
GO:0007631	Process	Feeding behavior	IEA
GO:0007631	Process	Feeding behavior	TAS	9491897
GO:0008188	Function	Neuropeptide receptor activity	TAS	9491897
GO:0010840	Process	Regulation of circadian sleep/wake cycle, wakefulness	ISS
GO:0016020	Component	Membrane	IEA
GO:0016499	Function	Orexin receptor activity	IBA
GO:0016499	Function	Orexin receptor activity	IDA	26950369
GO:0016499	Function	Orexin receptor activity	IEA
GO:0017046	Function	Peptide hormone binding	IEA
GO:0022410	Process	Circadian sleep/wake cycle process	IEA
GO:0032870	Process	Cellular response to hormone stimulus	IBA
GO:0040011	Process	Locomotion	IEA
GO:0045202	Component	Synapse	IEA
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IDA	26950369
GO:0051480	Process	Regulation of cytosolic calcium ion concentration	IEA

Other IDs

• MIM: 602393
• HGNC: 4849
• e!Ensembl: ENSG00000137252

Protein

• UniProt ID: O43614
• Protein name: Orexin receptor type 2 (Ox-2-R) (Ox2-R) (Ox2R) (Hypocretin receptor type 2)
• Protein function: Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides (PubMed:26950369, PubMed:9491897). Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding (PubMed:26950369, PubMed:9491897). {ECO:000026
• PDB: 4S0V, 5WQC, 5WS3, 6TPG, 6TPJ, 6TPN, 7L1U, 7L1V, 7SQO, 7SR8, 7XRR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00001	7tm_1	71 → 364	7 transmembrane receptor (rhodopsin family)	Family
  PF03827	Orexin_rec2	387 → 444	Orexin receptor type 2	Family

• Sequence:

  MSGTKLEDSPPCRNWSSASELNETQEPFLNPTDYDDEEFLRYLWREYLHPKEYEWVLIAG
  YIIVFVVALIGNVLVCVAVWKNHHMRTVTNYFIVNLSLADVLVTITCLPATLVVDITETW
  FFGQSLCKVIPYLQTVSVSVSVLTLSCIALDRWYAICHPLMFKSTAKRARNSIVIIWIVS
  CIIMIPQAIVMECSTVFPGLANKTTLFTVCDERWGGEIYPKMYHICFFLVTYMAPLCLMV
  LAYLQIFRKLWCRQIPGTSSVVQRKWKPLQPVSQPRGPGQPTKSRMSAVAAEIKQIRARR
  KTARMLMIVLLVFAICYLPISILNVLKRVFGMFAHTEDRETVYAWFTFSHWLVYANSAAN
  PIIYNFLSGKFREEFKAAFSCCCLGVHHRQEDRLTRGRTSTESRKSLTTQISNFDNISKL
  SEQVVLTSISTLPAANGAGPLQNW

• Sequence length: 444

Pathways

KEGG:

Neuroactive ligand-receptor interaction
Hormone signaling

Reactome:

Orexin and neuropeptides FF and QRFP bind to their respective receptors
G alpha (q) signalling events

Associated diseases

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
HCRTR2-related disorder	Benign; Likely benign; Conflicting classifications of pathogenicity	rs2653349, rs113561951, rs143272352, rs41271310, rs150493791, rs41381449, rs12111299, rs141299250	RCV003974558 RCV003914122 RCV003934076 RCV003941685 RCV003939756 RCV003939351 RCV003925872 RCV003920683

Associations from Text Mining
Disease Name	Relationship Type	References
Anorexia	Associate	28487995
Carcinoma Endometrioid	Associate	23482607
Cluster Headache	Associate	29318394, 30652302
Depressive Disorder	Associate	28487995
Endometrial Neoplasms	Associate	23482607
Glioblastoma	Associate	33470396
Goiter	Associate	26289589
Mental Disorders	Associate	36901420
Myotonic Dystrophy	Associate	18195268
Narcolepsy	Associate	22028875, 29220370
Neoplasms	Associate	23482607
Pain	Associate	26289589
Pain Postoperative	Associate	26289589
Personality Disorders	Associate	26289589
Sleep Wake Disorders	Associate	22028875, 33568662
Tobacco Use Disorder	Associate	26289589