Corticotropin releasing hormone receptor 2

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Corticotropin releasing hormone receptor 2
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM602034 MGI894312 HomoloGene55612 IUPHAR: 213 ChEMBL: 4069 GeneCards: CRHR2 Gene
RNA expression pattern
PBB GE CRHR2 207897 at tn.png
PBB GE CRHR2 211510 s at tn.png
More reference expression data
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 [1] [2]

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]

Biosynthesis and Properties[edit]

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[edit]


  1. ^ "Entrez Gene: CRHR2 corticotropin releasing hormone receptor 2". 
  2. ^ Pal K, Swaminathan K, Xu HE, Pioszak AA (December 2010). "Structural basis for hormone recognition by the Human CRFR2{alpha} G protein-coupled receptor". J. Biol. Chem. 285 (51): 40351–61. doi:10.1074/jbc.m110.186072. PMID 20966082. 
  3. ^ Catalano RD, Kyriakou T, Chen J, Easton A, Hillhouse EW (March 2003). "Regulation of corticotropin-releasing hormone type 2 receptors by multiple promoters and alternative splicing: identification of multiple splice variants". Mol. Endocrinol. 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". Front Horm Res 27: 66–74. doi:10.1159/000061042. PMID 11450436. 

Further reading[edit]

External links[edit]

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