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 MGI: 894312 HomoloGene: 55612 GeneCards: CRHR2
Gene location (Human)
Ideogram human chromosome 7.svg
Chr. Chromosome 7 (human) [1]
Human chromosome 7 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 7p14.3Start30,651,943 bp [1]
End30,700,129 bp [1]
RNA expression pattern
PBB GE CRHR2 207897 at fs.png

PBB GE CRHR2 211510 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

1395

12922

Ensembl

ENSG00000106113

ENSMUSG00000003476

UniProt

Q13324

Q60748

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: 55.09 – 55.13 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]

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

Corticotropin-releasing hormone protein-coding gene in the species Homo sapiens

Corticotropin-releasing hormone (CRH) is a peptide hormone involved in the stress response. 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 ACTH, as part of the HPA Axis.

G protein Type of proteins

G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases.

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.

An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature messenger RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome.

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]

Endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cis

The endoplasmic reticulum (ER) is a type of organelle found in eukaryotic cells that forms an interconnected network of flattened, membrane-enclosed sacs or tube-like structures known as cisternae. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum occurs in most types of eukaryotic cells, but is absent from red blood cells and spermatozoa.

See also

Related Research Articles

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.

Proopiomelanocortin protein-coding gene in the species Homo sapiens

Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in the pituitary from the 285-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-amino-acid-long signal peptide sequence during translation.

Corticotropin-releasing factor, CRF 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.

Gonadotropin-releasing hormone protein-coding gene in the species Homo sapiens

Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

Urocortin protein-coding gene in the species Homo sapiens

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.

Corticotropin-releasing hormone receptors (CRHRs), also known as corticotropin-releasing factor receptors (CRFRs) are a G protein-coupled receptor family that binds corticotropin-releasing hormone (CRH). There are two receptors in the family, designated as type 1 and 2, each encoded by a separate gene.

Growth hormone-binding protein (GHBP) is a soluble carrier protein for growth hormone (GH). The function of GHBP is still unknown. Current research suggests that the protein is associated with regulation of the GH supply in the circulatory system as well as GH receptor function.

Corticotropin-releasing hormone receptor 1 protein-coding gene in the species Homo sapiens

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.

Thyroid hormone receptor alpha protein-coding gene in the species Homo sapiens

Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the THRA gene.

CRHBP 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.

UCN2 protein-coding gene in the species Homo sapiens

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

UCN3 protein-coding gene in the species Homo sapiens

Urocortin-3 is a protein that in humans is encoded by the UCN3 gene.

Antalarmin 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.

Astressin-B (AST) is a nonselective corticotropin releasing hormone antagonist that reduces the synthesis of ACTH and cortisol.

Verucerfont 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 protein that functions as a neuropeptide. It is 40 amino acids in length, and has 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 sauvagei, but has been hypothesised to be produced endogenously by mammals, as it produces similar physiological effects to endogenous neuropeptides such as corticotropin-releasing hormone.

Emicerfont chemical compound

Emicerfont (GW-876,008) 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: CRF1 and CRF2. This then triggers the release of corticotropin (ACTH), another hormone which is involved in the physiological response to stress.

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:".
  4. ↑ "Mouse PubMed Reference:".
  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  Lock-green.svg. 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. Frontiers of Hormone Research. 27: 66–74. doi:10.1159/000061042. ISBN   3-8055-7195-X. PMID   11450436.

Further reading

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