Corticotropin-releasing hormone receptor 2

Last updated
CRHR2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CRHR2 , CRF-RB, CRF2, CRFR2, HM-CRF, corticotropin releasing hormone receptor 2
External IDs OMIM: 602034 MGI: 894312 HomoloGene: 55612 GeneCards: CRHR2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001202475
NM_001202481
NM_001202482
NM_001202483
NM_001883

Contents

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 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

Related Research Articles

<span class="mw-page-title-main">Adrenocorticotropic hormone</span> Pituitary hormone

Adrenocorticotropic hormone is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress. Its principal effects are increased production and release of cortisol and androgens by the cortex and medulla of the adrenal gland, respectively. ACTH is also related to the circadian rhythm in many organisms.

<span class="mw-page-title-main">Proopiomelanocortin</span> Mammalian protein found in Homo sapiens

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in corticotrophs of the anterior pituitary from the 267-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation. POMC is part of the central melanocortin system.

<span class="mw-page-title-main">Corticotropin-releasing hormone</span> Mammalian protein found in humans

Corticotropin-releasing hormone (CRH) is a peptide hormone involved in stress responses. It is a releasing hormone that belongs to corticotropin-releasing factor family. In humans, it is encoded by the CRH gene. Its main function is the stimulation of the pituitary synthesis of adrenocorticotropic hormone (ACTH), as part of the hypothalamic–pituitary–adrenal axis.

Corticotropin-releasing factor family, CRF family is a family of related neuropeptides in vertebrates. This family includes corticotropin-releasing hormone, urotensin-I, urocortin, and sauvagine. The family can be grouped into 2 separate paralogous lineages, with urotensin-I, urocortin and sauvagine in one group and CRH forming the other group. Urocortin and sauvagine appear to represent orthologues of fish urotensin-I in mammals and amphibians, respectively. The peptides have a variety of physiological effects on stress and anxiety, vasoregulation, thermoregulation, growth and metabolism, metamorphosis and reproduction in various species, and are all released as prohormones.

Corticotropes are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulating hormone (MSH). These cells are stimulated by corticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary. The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies of parvocellular neurosecretory cells within the paraventricular nucleus of the hypothalamus and passes to the corticotropes in the anterior pituitary via the hypophyseal portal system. Adrenocorticotropin hormone stimulates the adrenal cortex to release glucocorticoids and plays an important role in the stress response.

<span class="mw-page-title-main">Urocortin</span>

Urocortin is a protein that in humans is encoded by the UCN gene. Urocortin belongs to the corticotropin-releasing factor (CRF) family of proteins which includes CRF, urotensin I, sauvagine, urocortin II and urocortin III. Urocortin is involved in the mammalian stress response, and regulates aspects of appetite and stress response.

Urocortin 2 (Ucn2) is an endogenous peptide in the corticotrophin-releasing factor (CRF) family.

Urocortin III, a 38–41 amino acid peptide, is a member of the CRF, also known as CRH family of peptides, with a long evolutionary lineage.

Growth hormone-binding protein (GHBP) is a soluble carrier protein for growth hormone (GH). The full range of functions of GHBP remains to be determined however, current research suggests that the protein is associated with regulation of the GH availability and half-life in the circulatory system, as well as modulating GH receptor function.

<span class="mw-page-title-main">Somatostatin receptor 2</span> Protein-coding gene in the species Homo sapiens

Somatostatin receptor type 2 is a protein that in humans is encoded by the SSTR2 gene.

<span class="mw-page-title-main">Corticotropin-releasing hormone receptor 1</span> Protein and coding gene in humans

Corticotropin-releasing hormone receptor 1 (CRHR1) is a protein, also known as CRF1, with the latter (CRF1) now being the IUPHAR-recommended name. In humans, CRF1 is encoded by the CRHR1 gene at region 17q21.31, beside micrototubule-associated protein tau MAPT.

<span class="mw-page-title-main">CRHBP</span> Protein-coding gene in the species Homo sapiens

Corticotropin-releasing factor-binding protein is a protein that in humans is encoded by the CRHBP gene. It belongs to corticotropin-releasing hormone binding protein family.

<span class="mw-page-title-main">UCN2</span> Protein-coding gene in the species Homo sapiens

Urocortin-2 is a protein that in humans is encoded by the UCN2 gene.

<span class="mw-page-title-main">UCN3</span> Protein-coding gene in the species Homo sapiens

Urocortin-3 is a protein that, in humans, is encoded by the UCN3 gene. It belongs to the corticotropin-releasing hormone family.

<span class="mw-page-title-main">Antalarmin</span> Chemical compound

Antalarmin (CP-156,181) is a drug that acts as a CRH1 antagonist.

A Corticotropin-releasing hormone antagonist is a specific type of receptor antagonist that blocks the receptor sites for corticotropin-releasing hormone, also known as corticotropin-releasing factor (CRF), which synchronizes the behavioral, endocrine, autonomic, and immune responses to stress by controlling the hypothalamic-pituitary-adrenal axis. CRH antagonists thereby block the consequent secretions of ACTH and cortisol due to stress, among other effects.

Corticotropin-releasing hormone binding protein (CRH-BP) binds corticotropin-releasing hormone (CRH) and several related peptide hormones. It is an ancient, highly conserved protein whose origin predates the divergence of protostomes and deuterostomes.

<span class="mw-page-title-main">Astressin-B</span>

Astressin-B is a nonselective corticotropin releasing hormone antagonist that reduces the synthesis of adrenocorticotropic hormone and cortisol.

<span class="mw-page-title-main">Verucerfont</span> Chemical compound

Verucerfont (GSK-561,679) is a drug developed by GlaxoSmithKline which acts as a CRF-1 antagonist. Corticotropin releasing factor (CRF), also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress, and activates the two corticotropin-releasing hormone receptors CRH-1 and CRH-2. This then triggers the release of corticotropin (ACTH), another hormone which is involved in the physiological response to stress.

Sauvagine is a neuropeptide from the corticotropin-releasing factor (CRF) family of peptides and is orthologous to the mammalian hormone, urocortin 1, and the teleost fish hormone, urotensin 1. It is 40 amino acids in length, and has the sequence XGPPISIDLSLELLRKMIEIEKQEKEKQQAANNRLLLDTI-NH2, with a pyrrolidone carboxylic acid modification at the N-terminal and amidation of the C-terminal isoleucine residue. It was originally isolated from the skin of the frog Phyllomedusa sauvagii. Given its relation to other CRF-related peptides, it exerts similar physiological effects as corticotropin-releasing hormone.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000106113 - Ensembl, May 2017
  2. 1 2 3 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

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