Corticotropin-releasing hormone receptor 2

CRHR2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3N93, 3N95, 3N96
Identifiers
Aliases	CRHR2 , CRF-RB, CRF2, CRFR2, HM-CRF, corticotropin releasing hormone receptor 2
External IDs	OMIM: 602034; MGI: 894312; HomoloGene: 55612; GeneCards: CRHR2; OMA:CRHR2 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7p14.3 Start 30,651,942 bp [1] End 30,700,129 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6 B3|6 27.33 cM Start 55,067,034 bp [2] End 55,110,001 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle ganglionic eminence ventricular zone apex of heart anterior pituitary muscle of thigh right frontal lobe left ventricle gonad prefrontal cortex Top expressed in muscle of thigh masseter muscle skeletal muscle tissue soleus muscle lumbar spinal ganglion lip embryo esophagus intercostal muscle extraocular muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity protein binding corticotrophin-releasing factor receptor activity transmembrane signaling receptor activity peptide hormone binding corticotropin-releasing hormone receptor activity Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane axon dendrite axon terminus Biological process adenylate cyclase-modulating G protein-coupled receptor signaling pathway cell surface receptor signaling pathway signal transduction cellular response to corticotropin-releasing hormone stimulus G protein-coupled receptor signaling pathway hormone-mediated signaling pathway long-term potentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1395 12922 Ensembl ENSG00000106113 ENSMUSG00000003476 UniProt Q13324 Q60748 RefSeq (mRNA) NM_001202475 NM_001202481 NM_001202482 NM_001202483 NM_001883 NM_001288618 NM_001288619 NM_001288620 NM_009953 RefSeq (protein) NP_001189404 NP_001189410 NP_001189411 NP_001189412 NP_001874 NP_001275547 NP_001275548 NP_001275549 NP_034083 Location (UCSC) Chr 7: 30.65 – 30.7 Mb Chr 6: 55.07 – 55.11 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF₂, ^[5] that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF₂ receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF₂ receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF₂ receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH. ^[6]

Properties

The human CRHR2 gene contains 12 exons. Three major functional isoforms, alpha (411 amino acids), beta (438 amino acids), and gamma (397 amino acids), encoded by transcripts with alternative first exons, ^[7] differ only in the N-terminal sequence comprising the signal peptide and part of the extracellular domain (amino acids 18-108 of CRHR2 alpha); the unique N-terminal sequence of each isoform (34 amino acids in CRHR2 alpha; 61 amino acids in Hs CRHR2 beta; 20 amino acids in CRHR2 gamma) is followed by a sequence common to all isoforms (377 amino acids) ^[8] comprising most of the multi-pass transmembrane domain followed by a cytoplasmic domain of 47 amino acids.

CRHR2 beta is expressed in the human brain; CRHR2 alpha predominates in peripheral tissues. The N-terminal signal peptides of corticotropin-releasing hormone receptor 1 and CRHR2 beta are cleaved off in the endoplasmic reticulum to yield the mature receptors. In contrast, CRHR2 alpha contains a unique pseudo signal peptide that is not removed from the mature receptor. In adenylate cyclase activation assays, CRH-related peptides are 10 times more potent at stimulating CRHR2 beta than CRHR2 alpha and CRHR2 gamma, suggesting that the N-terminal sequence is involved in the ligand-receptor interaction. ^[9]

See also

• Corticotropin-releasing hormone receptor

References

1. GRCh38: Ensembl release 89: ENSG00000106113 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000003476 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: CRHR2 corticotropin releasing hormone receptor 2".
6. Pal K, Swaminathan K, Xu HE, Pioszak AA (Dec 2010). "Structural basis for hormone recognition by the Human CRFR2{alpha} G protein-coupled receptor". The Journal of Biological Chemistry. 285 (51): 40351–61. doi: 10.1074/jbc.m110.186072 . PMC   3001015 . PMID   20966082.
7. Catalano RD, Kyriakou T, Chen J, Easton A, Hillhouse EW (Mar 2003). "Regulation of corticotropin-releasing hormone type 2 receptors by multiple promoters and alternative splicing: identification of multiple splice variants". Molecular Endocrinology. 17 (3): 395–410. doi: 10.1210/me.2002-0302 . PMID   12554761.
8. "Corticotropin-releasing factor receptor 2, UniProtKB/Swiss-Prot Q13324 (CRFR2_HUMAN)".
9. Hillhouse EW, Grammatopoulos DK (2001). Control of intracellular signalling by corticotropin-releasing hormone in human myometrium. Frontiers of Hormone Research. Vol. 27. pp. 66–74. doi:10.1159/000061042. ISBN   3-8055-7195-X. PMID   11450436.

Further reading

• Perrin MH, Donaldson CJ, Chen R, Lewis KA, Vale WW (Dec 1993). "Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor". Endocrinology. 133 (6): 3058–61. doi:10.1210/endo.133.6.8243338. PMID   8243338.
• Liaw CW, Lovenberg TW, Barry G, Oltersdorf T, Grigoriadis DE, de Souza EB (Jan 1996). "Cloning and characterization of the human corticotropin-releasing factor-2 receptor complementary deoxyribonucleic acid". Endocrinology. 137 (1): 72–7. doi: 10.1210/endo.137.1.8536644 . PMID   8536644.
• Donaldson CJ, Sutton SW, Perrin MH, Corrigan AZ, Lewis KA, Rivier JE, Vaughan JM, Vale WW (May 1996). "Cloning and characterization of human urocortin". Endocrinology. 137 (5): 2167–70. doi: 10.1210/endo.137.5.8612563 . PMID   8612563.
• Meyer AH, Ullmer C, Schmuck K, Morel C, Wishart W, Lübbert H, Engels P (Feb 1997). "Localization of the human CRF2 receptor to 7p21-p15 by radiation hybrid mapping and FISH analysis". Genomics. 40 (1): 189–90. doi:10.1006/geno.1996.4521. PMID   9070940.
• Valdenaire O, Giller T, Breu V, Gottowik J, Kilpatrick G (May 1997). "A new functional isoform of the human CRF2 receptor for corticotropin-releasing factor". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1352 (2): 129–32. doi:10.1016/s0167-4781(97)00047-x. PMID   9199241.
• Gottowik J, Goetschy V, Henriot S, Kitas E, Fluhman B, Clerc RG, Moreau JL, Monsma FJ, Kilpatrick GJ (Oct 1997). "Labelling of CRF1 and CRF2 receptors using the novel radioligand, [3H]-urocortin". Neuropharmacology. 36 (10): 1439–46. doi:10.1016/S0028-3908(97)00098-1. PMID   9423932. S2CID   6235036.
• Kostich WA, Chen A, Sperle K, Largent BL (Aug 1998). "Molecular identification and analysis of a novel human corticotropin-releasing factor (CRF) receptor: the CRF2gamma receptor". Molecular Endocrinology. 12 (8): 1077–85. doi:10.1210/mend.12.8.0145. PMID   9717834.
• Willenberg HS, Bornstein SR, Hiroi N, Päth G, Goretzki PE, Scherbaum WA, Chrousos GP (Mar 2000). "Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function". Molecular Psychiatry. 5 (2): 137–41. doi: 10.1038/sj.mp.4000720 . PMID   10822340.
• Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, Hogenesch JB, Gulyas J, Rivier J, Vale WW, Sawchenko PE (Feb 2001). "Urocortin II: a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors". Proceedings of the National Academy of Sciences of the United States of America. 98 (5): 2843–8. Bibcode:2001PNAS...98.2843R. doi: 10.1073/pnas.051626398 . PMC   30227 . PMID   11226328.
• Hsu SY, Hsueh AJ (May 2001). "Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor". Nature Medicine. 7 (5): 605–11. doi:10.1038/87936. PMID   11329063. S2CID   22916906.
• Lewis K, Li C, Perrin MH, Blount A, Kunitake K, Donaldson C, Vaughan J, Reyes TM, Gulyas J, Fischer W, Bilezikjian L, Rivier J, Sawchenko PE, Vale WW (Jun 2001). "Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor". Proceedings of the National Academy of Sciences of the United States of America. 98 (13): 7570–5. Bibcode:2001PNAS...98.7570L. doi: 10.1073/pnas.121165198 . PMC   34709 . PMID   11416224.
• Wetzka B, Sehringer B, Schäfer WR, Biller S, Hör C, Benedek E, Deppert WR, Zahradnik HP (May 2003). "Expression patterns of CRH, CRH receptors, and CRH binding protein in human gestational tissue at term". Experimental and Clinical Endocrinology & Diabetes. 111 (3): 154–61. doi:10.1055/s-2003-39778. PMID   12784189.
• Karteris E, Hillhouse EW, Grammatopoulos D (Feb 2004). "Urocortin II is expressed in human pregnant myometrial cells and regulates myosin light chain phosphorylation: potential role of the type-2 corticotropin-releasing hormone receptor in the control of myometrial contractility". Endocrinology. 145 (2): 890–900. doi: 10.1210/en.2003-1210 . PMID   14592950.
• Seres J, Bornstein SR, Seres P, Willenberg HS, Schulte KM, Scherbaum WA, Ehrhart-Bornstein M (Feb 2004). "Corticotropin-releasing hormone system in human adipose tissue". The Journal of Clinical Endocrinology and Metabolism. 89 (2): 965–70. doi: 10.1210/jc.2003-031299 . PMID   14764822.
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW (Jun 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nature Biotechnology. 22 (6): 707–16. doi:10.1038/nbt971. PMID   15146197. S2CID   27764390.
• Nanda SA, Roseboom PH, Nash GA, Speers JM, Kalin NH (Dec 2004). "Characterization of the human corticotropin-releasing factor2(a) receptor promoter: regulation by glucocorticoids and the cyclic adenosine 5'-monophosphate pathway". Endocrinology. 145 (12): 5605–15. doi: 10.1210/en.2004-0907 . PMID   15331578.
• "Corticotropin-releasing Factor Receptors: CRF₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2015-12-22. Retrieved 2008-12-04.

External links

• Receptors, Corticotropin-Releasing Hormone at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt : Q60748 (Mouse Corticotropin-releasing factor receptor 2) at the PDBe-KB .

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