Orexin/Hypocretin receptor type 1

Function

G protein-coupled receptor that binds the neuropeptide orexin-A with high affinity, and orexin-B with lower affinity, two peptides derived from a common precursor, prepro-orexin. Its activity is mediated via a G(q)-protein-coupled pathway, which activates the phosphatidylinositol-calcium second messenger system in response to orexin-A binding. In addition to G(q)-mediated signaling, orexin-A stimulation also promotes beta-arrestin recruitment, leading to receptor internalization. Plays a significant role in the regulation of food intake (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Orexin_rcpt, OX1R

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 14

• 4ZJ8 X-ray 2.75A
• 4ZJC X-ray 2.83A
• 6TO7 X-ray 2.26A
• 6TOD X-ray 2.11A
• 6TOS X-ray 2.13A
• 6TOT X-ray 2.22A
• 6TP3 X-ray 3.04A
• 6TP4 X-ray 3.01A
• 6TP6 X-ray 2.34A
• 6TQ4 X-ray 2.30A
• 6TQ6 X-ray 2.55A
• 6TQ7 X-ray 2.66A
• … and 2 more

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0005886 plasma membrane
• GO:0045202 synapse
• GO:0004930 G protein-coupled receptor activity
• GO:0016499 orexin receptor activity
• GO:0017046 peptide hormone binding
• GO:0032870 cellular response to hormone stimulus
• GO:0007268 chemical synaptic transmission
• GO:0007631 feeding behavior
• GO:0007218 neuropeptide signaling pathway
• GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
• GO:0051480 regulation of cytosolic calcium ion concentration

Drugs targeting this protein · 7

• SUVOREXANT antagonist
• SB-649868 antagonist
• FILOREXANT antagonist
• LEMBOREXANT antagonist
• DARIDOREXANT antagonist
• ALMOREXANT antagonist
• DARIDOREXANT HYDROCHLORIDE antagonist

Related proteins · sequence + function similarity

• Orexin/Hypocretin receptor type 1 1.00
• Orexin/Hypocretin receptor type 1 1.00
• Orexin/Hypocretin receptor type 1 1.00
• Orexin/Hypocretin receptor type 1 0.99
• Neuropeptide FF receptor 1 0.94
• Neuropeptide FF receptor 1 0.92
• Orexin receptor type 2 0.90
• Orexin receptor type 2 0.89
• Orexin receptor type 2 0.88
• Orexin receptor type 2 0.88
• Orexin receptor type 2 0.88
• Prolactin-releasing peptide receptor 0.86

Co-cited proteins · studied together in the literature

• Orexin receptor type 2 4 shared papers
• Hypocretin neuropeptide precursor 2 shared papers
• Orexin receptor type 2 1 shared papers
• Hypocretin neuropeptide precursor 1 shared papers
• Orexin/Hypocretin receptor type 1 1 shared papers
• Hypocretin neuropeptide precursor 1 shared papers
• Hypocretin neuropeptide precursor 1 shared papers

Literature · 10 cited papers

• Structure-based development of a subtype-selective orexin 1 receptor antagonist. Proc. Natl. Acad. Sci. U.S.A. · 2020
• Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis. J. Med. Chem. · 2020
• Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors. Nat. Struct. Mol. Biol. · 2016
• The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
• The sustainability of interactions between the orexin-1 receptor and beta-arrestin-2 is defined by a single C-terminal cluster of hydroxy amino acids and modulates the kinetics of ERK MAPK regulation. Biochem. J. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Polymorphisms in hypocretin/orexin pathway genes and narcolepsy. Neurology · 2001
• A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat. Med. · 2000
• Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell · 1998