Growth hormone receptor

GHR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A22, 1AXI, 1HWG, 1HWH, 1KF9, 2AEW, 3HHR
Identifiers
Aliases	GHR, GHBP, GHIP, growth hormone receptor
External IDs	OMIM: 600946 MGI: 95708 HomoloGene: 134 GeneCards: GHR
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p13.1-p12 Start 42,423,439 bp[1] End 42,721,878 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 A1|15 1.84 cM Start 3,347,242 bp[2] End 3,612,974 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in deltoid muscle vastus lateralis muscle liver Achilles tendon tibialis anterior muscle triceps brachii muscle adipose tissue right lobe of liver thoracic diaphragm glomerulus Top expressed in proximal tubule white adipose tissue left lobe of liver kidney intercostal muscle subcutaneous adipose tissue ankle sternocleidomastoid muscle triceps brachii muscle temporal muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity growth factor binding peptide hormone binding protein binding cytokine receptor activity proline-rich region binding protein kinase binding identical protein binding growth hormone receptor activity cytokine binding Cellular component integral component of membrane membrane receptor complex integral component of plasma membrane extracellular region cell surface growth hormone receptor complex extracellular space cytosol plasma membrane cytoplasmic ribonucleoprotein granule external side of plasma membrane Biological process insulin-like growth factor receptor signaling pathway receptor signaling pathway via JAK-STAT growth hormone receptor signaling pathway via JAK-STAT response to estradiol endocytosis allantoin metabolic process regulation of multicellular organism growth cytokine-mediated signaling pathway citrate metabolic process receptor internalization response to cycloheximide 2-oxoglutarate metabolic process creatinine metabolic process oxaloacetate metabolic process fatty acid metabolic process succinate metabolic process cellular response to hormone stimulus growth hormone receptor signaling pathway taurine metabolic process valine metabolic process positive regulation of multicellular organism growth positive regulation of peptidyl-tyrosine phosphorylation creatine metabolic process isoleucine metabolic process positive regulation of tyrosine phosphorylation of STAT protein activation of Janus kinase activity hormone metabolic process positive regulation of receptor signaling pathway via JAK-STAT Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2690 14600 Ensembl ENSG00000112964 ENSMUSG00000055737 UniProt P10912 P16882 RefSeq (mRNA) NM_000163 NM_001242399 NM_001242400 NM_001242401 NM_001242402 NM_001242403 NM_001242404 NM_001242405 NM_001242406 NM_001242460 NM_001242461 NM_001242462 NM_001048147 NM_001048178 NM_010284 NM_001286370 RefSeq (protein) NP_000154 NP_001229328 NP_001229329 NP_001229330 NP_001229331 NP_001229332 NP_001229333 NP_001229334 NP_001229335 NP_001229389 NP_001229391 NP_001041643 NP_001273299 NP_034414 Location (UCSC) Chr 5: 42.42 – 42.72 Mb Chr 15: 3.35 – 3.61 Mb PubMed search [3] [4]
Wikidata
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Growth hormone receptor is a protein that in humans is encoded by the GHR gene.^[5] GHR orthologs^[6] have been identified in most mammals.

Structure

Growth hormone receptor (GHR) is a transmembrane protein consisting of 620 amino acids. The receptor is part of the Type I cytokine receptor family of receptors. GHR exists in two forms as a full length membrane-bound receptor and as a soluble GH binding protein (GHBP).^[7][8] GHR contains two fibronectin type III β domains in its extracellular domain, whereas the intracellular domain contains tyrosine Kinase JAK2 binding sites for SH2 proteins. JAK2 is the primary signal transducer for growth hormone.^[9]

Function

This gene encodes a protein that is a transmembrane receptor for growth hormone.^[10][11] Binding of growth hormone to the receptor leads to reorientation of a pre-assembled receptor dimer dimerization (the receptor may however also exist as monomers on the cell surface ^[12]) and the activation of an intra- and intercellular signal transduction pathway leading to growth.^[13] A common alternate allele of this gene, called GHRd3, lacks exon three and has been well characterized. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature (proportional dwarfism). Other splice variants, including one encoding a soluble form of the protein (GHRtr), have been observed but have not been thoroughly characterized.^[5] Laron mice (that is mice genetically engineered to carry defective Ghr), have a dramatic reduction in body mass (only reaching 50% of the weight of normal siblings), and also show a ~40% increase in lifespan.

Interactions

Growth hormone receptor has been shown to interact with SGTA,^[15] PTPN11,^[16][17] Janus kinase 2,^[18][19][20] Suppressor of cytokine signaling 1^[21] and CISH.^[21]

Evolution

The GHR gene is used in animals as a nuclear DNA phylogenetic marker.^[6] The exon 10 has first been experienced to explore the phylogeny of the major groups of Rodentia.^[22][23][24] GHR has also proven useful at lower taxonomic levels, e.g., in octodontoid,^[25][14] arvicoline,^[26] muroid,^[27][28] murine,^[29] and peromyscine ^[30] rodents, in arctoid ^[31] and felid^[32] carnivores, and in dermopterans.^[33] Note that the GHR intron 9 has also been used to investigate the mustelid^[34] and hyaenid ^[35] carnivores phylogenetics.

Antagonists

Growth hormone receptor antagonists such as pegvisomant (trade name Somavert) are used in the treatment of acromegaly.^[36] They are used if the tumor of the pituitary gland causing the acromegaly cannot be controlled with surgery or radiation, and the use of somatostatin analogues is unsuccessful. Pegvisomant is delivered as a powder that is mixed with water and injected under the skin.^[37]

See also

• Hypothalamic–pituitary–somatic axis

References

External links

• Somatotropin+receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Illustration at nih.gov
• Overview
• Growth Hormone Receptor Archived 2015-10-16 at the Wayback Machine: Molecule of the Month by Shuchismita Dutta and David Goodsell (April 2004)
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Growth hormone receptor