Corticotropin releasing hormone receptor 2

Corticotropin releasing hormone receptor 2
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3N93​, 3N95​, 3N96​
Identifiers
Symbols	CRHR2 ; CRF-RB; CRF2; CRFR2; HM-CRF
External IDs	OMIM: 602034 MGI: 894312 HomoloGene: 55612 IUPHAR: 213 ChEMBL: 4069 GeneCards: CRHR2 Gene
Gene ontology Molecular function • hormone activity • protein binding • corticotrophin-releasing factor receptor activity • peptide hormone binding • corticotropin-releasing hormone receptor activity Cellular component • rough endoplasmic reticulum • Golgi apparatus • plasma membrane • integral component of plasma membrane • cell surface • dendrite • varicosity • perikaryon • axon terminus • cell body fiber Biological process • actin filament organization • cell surface receptor signaling pathway • adenylate cyclase-modulating G-protein coupled receptor signaling pathway • protein kinase C-activating G-protein coupled receptor signaling pathway • hormone-mediated signaling pathway • positive regulation of heart rate • negative regulation of gene expression • negative regulation of norepinephrine secretion • positive regulation of serotonin secretion • negative regulation of angiogenesis • sensory perception of pain • cerebellum development • hypothalamus development • negative regulation of cAMP biosynthetic process • positive regulation of cAMP biosynthetic process • epithelial cell differentiation • positive regulation of interleukin-6 production • negative regulation of epinephrine secretion • positive regulation of stress-activated MAPK cascade • negative regulation of luteinizing hormone secretion • gastric motility • catecholamine biosynthetic process • positive regulation of cAMP-mediated signaling • negative regulation of cAMP-mediated signaling • positive regulation of blood pressure • negative regulation of follicle-stimulating hormone secretion • skeletal muscle tissue growth • positive regulation of NF-kappaB transcription factor activity • long-term synaptic potentiation • negative regulation of insulin secretion involved in cellular response to glucose stimulus • regulation of ERK1 and ERK2 cascade • cellular response to corticotropin-releasing hormone stimulus • cellular response to glucocorticoid stimulus • negative regulation of calcium ion import • negative regulation of feeding behavior • negative regulation of defecation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1395	12922
Ensembl	ENSG00000106113	ENSMUSG00000003476
UniProt	Q13324	Q60748
RefSeq (mRNA)	NM_001202475	NM_001288618
RefSeq (protein)	NP_001189404	NP_001275547
Location (UCSC)	Chr 7: 30.65 – 30.7 Mb	Chr 6: 55.09 – 55.13 Mb
PubMed search

Corticotropin releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF₂,^[1] 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.^[2]

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,^[3] 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)^[4] comprising most of the multi-pass transmembrane domain followed by a cytoplasmic domain of 47 amino acids.

CRHR2 beta is expressed in 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.^[5]

See also

• Corticotropin releasing hormone receptor

References

1. "Entrez Gene: CRHR2 corticotropin releasing hormone receptor 2".
2. 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. PMID 20966082.
3. 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.
4. "Corticotropin-releasing factor receptor 2, UniProtKB/Swiss-Prot Q13324 (CRFR2_HUMAN)".
5. Hillhouse EW, Grammatopoulos DK (2001). "Control of intracellular signalling by corticotropin-releasing hormone in human myometrium". Frontiers of Hormone Research 27: 66–74. doi:10.1159/000061042. 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/en.133.6.3058. 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/en.137.1.72. 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/en.137.5.2167. 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 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.
• 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/me.12.8.1077. 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. 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.
• 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. 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.
• 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.

External links

• "Corticotropin-releasing Factor Receptors: CRF₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• Corticotropin-releasing hormone receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

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