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0  structures 37  species 0  interactions 46  sequences 2  architectures

Family: Orexin_rec2 (PF03827)

Summary: Orexin receptor type 2

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This is the Wikipedia entry entitled "Hypocretin (orexin) receptor 2". More...

Hypocretin (orexin) receptor 2 Edit Wikipedia article

Hypocretin (orexin) receptor 2
Identifiers
Symbols HCRTR2; OX2R
External IDs OMIM602393 MGI2680765 HomoloGene1168 IUPHAR: OX2 ChEMBL: 4792 GeneCards: HCRTR2 Gene
RNA expression pattern
PBB GE HCRTR2 207393 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3062 387285
Ensembl ENSG00000137252 ENSMUSG00000032360
UniProt O43614 P58308
RefSeq (mRNA) NM_001526 NM_198962
RefSeq (protein) NP_001517 NP_945200
Location (UCSC) Chr 6:
55.04 – 55.15 Mb
Chr 9:
76.23 – 76.32 Mb
PubMed search [1] [2]
Orexin receptor type 2
Identifiers
Symbol Orexin_rec2
Pfam PF03827
InterPro IPR004060

Orexin receptor type 2 (Ox2R or OX2), also known as hypocretin receptor type 2, is a protein that in humans is encoded by the HCRTR2 gene.[1]

Function[edit]

OX2 is a G-protein coupled receptor expressed exclusively in the brain. It has 64% identity with OX1. OX2 binds both orexin A and orexin B neuropeptides. OX2 is involved in the central feedback mechanism that regulates feeding behaviour.[1]

Ligands[edit]

Agonists[edit]

Antagonists[edit]

See also[edit]

References[edit]

  1. ^ a b "Entrez Gene: HCRTR2 hypocretin (orexin) receptor 2". 
  2. ^ McAtee LC, Sutton SW, Rudolph DA, Li X, Aluisio LE, Phuong VK, Dvorak CA, Lovenberg TW, Carruthers NI, Jones TK (August 2004). "Novel substituted 4-phenyl-[1,3]dioxanes: potent and selective orexin receptor 2 (OX(2)R) antagonists". Bioorg. Med. Chem. Lett. 14 (16): 4225–9. doi:10.1016/j.bmcl.2004.06.032. PMID 15261275. 
  3. ^ Cole AG, Stroke IL, Qin LY, Hussain Z, Simhadri S, Brescia MR, Waksmunski FS, Strohl B, Tellew JE, Williams JP, Saunders J, Appell KC, Henderson I, Webb ML (October 2008). "Synthesis of (3,4-dimethoxyphenoxy)alkylamino acetamides as orexin-2 receptor antagonists". Bioorg. Med. Chem. Lett. 18 (20): 5420–3. doi:10.1016/j.bmcl.2008.09.038. PMID 18815029. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Orexin receptor". More...

Orexin receptor Edit Wikipedia article

hypocretin (orexin) receptor 1
Identifiers
Symbol HCRTR1
Entrez 3061
HUGO 4848
OMIM 602392
RefSeq NM_001525
UniProt O43613
Other data
Locus Chr. 1 p33
hypocretin (orexin) receptor 2
Identifiers
Symbol HCRTR2
Entrez 3062
HUGO 4849
OMIM 602393
RefSeq NM_001526
UniProt O43614
Other data
Locus Chr. 6 p11-q11
Orexin receptor type 2
Identifiers
Symbol Orexin_rec2
Pfam PF03827
InterPro IPR004060

The orexin receptor (also referred to as the hypocretin receptor) is a G-protein-coupled receptor that binds the neuropeptide hormone orexin. There are two variants, OX1 and OX2, each encoded by a different gene (HCRTR1, HCRTR2).[1]

Both orexin receptors exhibit a similar pharmacology - the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors.[2]

Several orexin receptor antagonists are in development for potential use in sleep disorders.

References[edit]

  1. ^ Spinazzi R, Andreis PG, Rossi GP, Nussdorfer GG (2006). "Orexins in the regulation of the hypothalamic-pituitary-adrenal axis". Pharmacol. Rev. 58 (1): 46–57. doi:10.1124/pr.58.1.4. PMID 16507882. 
  2. ^ Smart D, Jerman JC, Brough SJ, Rushton SL, Murdock PR, Jewitt F, Elshourbagy NA, Ellis CE, Middlemiss DN, Brown F (September 1999). "Characterization of recombinant human orexin receptor pharmacology in a Chinese hamster ovary cell-line using FLIPR". Br. J. Pharmacol. 128 (1): 1–3. doi:10.1038/sj.bjp.0702780. PMC 1571615. PMID 10498827. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR004060

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004060

G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. We use the term clan to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PUBMED:8170923]. The currently known clan members include the rhodopsin-like GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs (http://www.gpcr.org/7tm/).

The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [PUBMED:2111655, PUBMED:2830256, PUBMED:8386361].

The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis [PUBMED:9491897]. A new family of neuropeptides, orexins, have been identified that bind and activate two closely related (previously) orphan GPCRs [PUBMED:9491897, PUBMED:9656726]. Orexins stimulate appetite and food consumption [PUBMED:9656726]. Their genes are expressed bilaterally and symmetrically in the lateral hypothalamus, which has been shown to be the "feeding centre". By contrast, the "satiety centre" is expressed in the ventromedial hypothalamus and is dominated by the leptin-regulated neuropeptide network.

Both orexin receptors exhibit a similar pharmacology - the 2 orexin peptides, orexin-A and orexin-B, bind to both receptors and, in each case, agonist binding results in an increase in intracellular calcium levels. However, orexin-B shows a 10-fold selectivity for orexin receptor type 2, whilst orexin-A is equipotent at both receptors [PUBMED:10498827].

Gene Ontology

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Domain organisation

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Alignments

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  Seed
(3)
Full
(46)
Representative proteomes NCBI
(36)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(12)
RP75
(28)
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  Seed
(3)
Full
(46)
Representative proteomes NCBI
(36)
Meta
(0)
RP15
(1)
RP35
(4)
RP55
(12)
RP75
(28)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Seed source: PRINTS
Previous IDs: none
Type: Family
Author: Griffiths-Jones SR
Number in seed: 3
Number in full: 46
Average length of the domain: 57.30 aa
Average identity of full alignment: 70 %
Average coverage of the sequence by the domain: 13.61 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 28.2 27.0
Noise cut-off 21.9 18.7
Model length: 61
Family (HMM) version: 8
Download: download the raw HMM for this family

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