Growth hormone receptor

Details

Name
Growth hormone receptor
Synonyms
  • GH receptor
  • Somatotropin receptor
Gene Name
GHR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000150|Growth hormone receptor
MDLWQLLLTLALAGSSDAFSGSEATAAILSRAPWSLQSVNPGLKTNSSKEPKFTKCRSPE
RETFSCHWTDEVHHGTKNLGPIQLFYTRRNTQEWTQEWKECPDYVSAGENSCYFNSSFTS
IWIPYCIKLTSNGGTVDEKCFSVDEIVQPDPPIALNWTLLNVSLTGIHADIQVRWEAPRN
ADIQKGWMVLEYELQYKEVNETKWKMMDPILTTSVPVYSLKVDKEYEVRVRSKQRNSGNY
GEFSEVLYVTLPQMSQFTCEEDFYFPWLLIIIFGIFGLTVMLFVFLFSKQQRIKMLILPP
VPVPKIKGIDPDLLKEGKLEEVNTILAIHDSYKPEFHSDDSWVEFIELDIDEPDEKTEES
DTDRLLSSDHEKSHSNLGVKDGDSGRTSCCEPDILETDFNANDIHEGTSEVAQPQRLKGE
ADLLCLDQKNQNNSPYHDACPATQQPSVIQAEKNKPQPLPTEGAESTHQAAHIQLSNPSS
LSNIDFYAQVSDITPAGSVVLSPGQKNKAGMSQCDMHPEMVSLCQENFLMDNAYFCEADA
KKCIPVAPHIKVESHIQPSLNQEDIYITTESLTTAAGRPGTGEHVPGSEMPVPDYTSIHI
VQSPQGLILNATALPLPDKEFLSSCGYVSTDQLNKIMP
Number of residues
638
Molecular Weight
71498.885
Theoretical pI
4.51
GO Classification
Functions
cytokine receptor activity / growth factor binding / peptide hormone binding / proline-rich region binding / protein homodimerization activity / protein kinase binding
Processes
2-oxoglutarate metabolic process / activation of JAK2 kinase activity / activation of MAPK activity / allantoin metabolic process / cellular response to hormone stimulus / citrate metabolic process / creatine metabolic process / creatinine metabolic process / endocytosis / fatty acid metabolic process / growth hormone receptor signaling pathway / insulin-like growth factor receptor signaling pathway / isoleucine metabolic process / JAK-STAT cascade / JAK-STAT cascade involved in growth hormone signaling pathway / multicellular organismal metabolic process / oxaloacetate metabolic process / positive regulation of multicellular organism growth / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of tyrosine phosphorylation of Stat3 protein / positive regulation of tyrosine phosphorylation of Stat5 protein / receptor internalization / regulation of multicellular organism growth / response to cycloheximide / response to estradiol / succinate metabolic process / taurine metabolic process / valine metabolic process
Components
cell surface / extracellular region / extracellular space / growth hormone receptor complex / integral component of membrane / integral component of plasma membrane / intracellular / plasma membrane / receptor complex
General Function
Protein kinase binding
Specific Function
Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to the JAK2/STAT5 pathway (By similarity).The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.Isoform 2 up-regulates the production of GHBP and acts as a negative inhibitor of GH signaling.
Pfam Domain Function
Transmembrane Regions
265-288
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010152|Growth hormone receptor (GHR)
ATGGATCTCTGGCAGCTGCTGTTGACCTTGGCACTGGCAGGATCAAGTGATGCTTTTTCT
GGAAGTGAGGCCACAGCAGCTATCCTTAGCAGAGCACCCTGGAGTCTGCAAAGTGTTAAT
CCAGGCCTAAAGACAAATTCTTCTAAGGAGCCTAAATTCACCAAGTGCCGTTCACCTGAG
CGAGAGACTTTTTCATGCCACTGGACAGATGAGGTTCATCATGGTACAAAGAACCTAGGA
CCCATACAGCTGTTCTATACCAGAAGGAACACTCAAGAATGGACTCAAGAATGGAAAGAA
TGCCCTGATTATGTTTCTGCTGGGGAAAACAGCTGTTACTTTAATTCATCGTTTACCTCC
ATCTGGATACCTTATTGTATCAAGCTAACTAGCAATGGTGGTACAGTGGATGAAAAGTGT
TTCTCTGTTGATGAAATAGTGCAACCAGATCCACCCATTGCCCTCAACTGGACTTTACTG
AACGTCAGTTTAACTGGGATTCATGCAGATATCCAAGTGAGATGGGAAGCACCACGCAAT
GCAGATATTCAGAAAGGATGGATGGTTCTGGAGTATGAACTTCAATACAAAGAAGTAAAT
GAAACTAAATGGAAAATGATGGACCCTATATTGACAACATCAGTTCCAGTGTACTCATTG
AAAGTGGATAAGGAATATGAAGTGCGTGTGAGATCCAAACAACGAAACTCTGGAAATTAT
GGCGAGTTCAGTGAGGTGCTCTATGTAACACTTCCTCAGATGAGCCAATTTACATGTGAA
GAAGATTTCTACTTTCCATGGCTCTTAATTATTATCTTTGGAATATTTGGGCTAACAGTG
ATGCTATTTGTATTCTTATTTTCTAAACAGCAAAGGATTAAAATGCTGATTCTGCCCCCA
GTTCCAGTTCCAAAGATTAAAGGAATCGATCCAGATCTCCTCAAGGAAGGAAAATTAGAG
GAGGTGAACACAATCTTAGCCATTCATGATAGCTATAAACCCGAATTCCACAGTGATGAC
TCTTGGGTTGAATTTATTGAGCTAGATATTGATGAGCCAGATGAAAAGACTGAGGAATCA
GACACAGACAGACTTCTAAGCAGTGACCATGAGAAATCACATAGTAACCTAGGGGTGAAG
GATGGCGACTCTGGACGTACCAGCTGTTGTGAACCTGACATTCTGGAGACTGATTTCAAT
GCCAATGACATACATGAGGGTACCTCAGAGGTTGCTCAGCCACAGAGGTTAAAAGGGGAA
GCAGATCTCTTATGCCTTGACCAGAAGAATCAAAATAACTCACCTTATCATGATGCTTGC
CCTGCTACTCAGCAGCCCAGTGTTATCCAAGCAGAGAAAAACAAACCACAACCACTTCCT
ACTGAAGGAGCTGAGTCAACTCACCAAGCTGCCCATATTCAGCTAAGCAATCCAAGTTCA
CTGTCAAACATCGACTTTTATGCCCAGGTGAGCGACATTACACCAGCAGGTAGTGTGGTC
CTTTCCCCGGGCCAAAAGAATAAGGCAGGGATGTCCCAATGTGACATGCACCCGGAAATG
GTCTCACTCTGCCAAGAAAACTTCCTTATGGACAATGCCTACTTCTGTGAGGCAGATGCC
AAAAAGTGCATCCCTGTGGCTCCTCACATCAAGGTTGAATCACACATACAGCCAAGCTTA
AACCAAGAGGACATTTACATCACCACAGAAAGCCTTACCACTGCTGCTGGGAGGCCTGGG
ACAGGAGAACATGTTCCAGGTTCTGAGATGCCTGTCCCAGACTATACCTCCATTCATATA
GTACAGTCCCCACAGGGCCTCATACTCAATGCGACTGCCTTGCCCTTGCCTGACAAAGAG
TTTCTCTCATCATGTGGCTATGTGAGCACAGACCAACTGAACAAAATCATGCCTTAG
Chromosome Location
5
Locus
5p13-p12
External Identifiers
ResourceLink
UniProtKB IDP10912
UniProtKB Entry NameGHR_HUMAN
GenBank Protein ID31738
GenBank Gene IDX06562
GenAtlas IDGHR
HGNC IDHGNC:4263
General References
  1. Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI: Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987 Dec 10-16;330(6148):537-43. [Article]
  2. Godowski PJ, Leung DW, Meacham LR, Galgani JP, Hellmiss R, Keret R, Rotwein PS, Parks JS, Laron Z, Wood WI: Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8083-7. [Article]
  3. Urbanek M, MacLeod JN, Cooke NE, Liebhaber SA: Expression of a human growth hormone (hGH) receptor isoform is predicted by tissue-specific alternative splicing of exon 3 of the hGH receptor gene transcript. Mol Endocrinol. 1992 Feb;6(2):279-87. [Article]
  4. Dastot F, Sobrier ML, Duquesnoy P, Duriez B, Goossens M, Amselem S: Alternatively spliced forms in the cytoplasmic domain of the human growth hormone (GH) receptor regulate its ability to generate a soluble GH-binding protein. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10723-8. [Article]
  5. Amit T, Bergman T, Dastot F, Youdim MB, Amselem S, Hochberg Z: A membrane-fixed, truncated isoform of the human growth hormone receptor. J Clin Endocrinol Metab. 1997 Nov;82(11):3813-7. [Article]
  6. Ross RJ, Esposito N, Shen XY, Von Laue S, Chew SL, Dobson PR, Postel-Vinay MC, Finidori J: A short isoform of the human growth hormone receptor functions as a dominant negative inhibitor of the full-length receptor and generates large amounts of binding protein. Mol Endocrinol. 1997 Mar;11(3):265-73. [Article]
  7. Urbanek M, Russell JE, Cooke NE, Liebhaber SA: Functional characterization of the alternatively spliced, placental human growth hormone receptor. J Biol Chem. 1993 Sep 5;268(25):19025-32. [Article]
  8. Pantel J, Machinis K, Sobrier ML, Duquesnoy P, Goossens M, Amselem S: Species-specific alternative splice mimicry at the growth hormone receptor locus revealed by the lineage of retroelements during primate evolution. J Biol Chem. 2000 Jun 23;275(25):18664-9. [Article]
  9. Fuh G, Mulkerrin MG, Bass S, McFarland N, Brochier M, Bourell JH, Light DR, Wells JA: The human growth hormone receptor. Secretion from Escherichia coli and disulfide bonding pattern of the extracellular binding domain. J Biol Chem. 1990 Feb 25;265(6):3111-5. [Article]
  10. Conte F, Salles JP, Raynal P, Fernandez L, Molinas C, Tauber M, Bieth E: Identification of a region critical for proteolysis of the human growth hormone receptor. Biochem Biophys Res Commun. 2002 Jan 18;290(2):851-7. [Article]
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  12. de Vos AM, Ultsch M, Kossiakoff AA: Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992 Jan 17;255(5042):306-12. [Article]
  13. Sundstrom M, Lundqvist T, Rodin J, Giebel LB, Milligan D, Norstedt G: Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution. J Biol Chem. 1996 Dec 13;271(50):32197-203. [Article]
  14. Amselem S, Duquesnoy P, Attree O, Novelli G, Bousnina S, Postel-Vinay MC, Goossens M: Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med. 1989 Oct 12;321(15):989-95. [Article]
  15. Kou K, Lajara R, Rotwein P: Amino acid substitutions in the intracellular part of the growth hormone receptor in a patient with the Laron syndrome. J Clin Endocrinol Metab. 1993 Jan;76(1):54-9. [Article]
  16. Amselem S, Duquesnoy P, Duriez B, Dastot F, Sobrier ML, Valleix S, Goossens M: Spectrum of growth hormone receptor mutations and associated haplotypes in Laron syndrome. Hum Mol Genet. 1993 Apr;2(4):355-9. [Article]
  17. Edery M, Rozakis-Adcock M, Goujon L, Finidori J, Levi-Meyrueis C, Paly J, Djiane J, Postel-Vinay MC, Kelly PA: Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism. J Clin Invest. 1993 Mar;91(3):838-44. [Article]
  18. Duquesnoy P, Sobrier ML, Duriez B, Dastot F, Buchanan CR, Savage MO, Preece MA, Craescu CT, Blouquit Y, Goossens M, et al.: A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization. EMBO J. 1994 Mar 15;13(6):1386-95. [Article]
  19. Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, Rundle AC, Wells JA, Carlsson LM: Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med. 1995 Oct 26;333(17):1093-8. [Article]
  20. Sobrier ML, Dastot F, Duquesnoy P, Kandemir N, Yordam N, Goossens M, Amselem S: Nine novel growth hormone receptor gene mutations in patients with Laron syndrome. J Clin Endocrinol Metab. 1997 Feb;82(2):435-7. [Article]
  21. Walker JL, Crock PA, Behncken SN, Rowlinson SW, Nicholson LM, Boulton TJ, Waters MJ: A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab. 1998 Jul;83(7):2554-61. [Article]
  22. Sanchez JE, Perera E, Baumbach L, Cleveland WW: Growth hormone receptor mutations in children with idiopathic short stature. J Clin Endocrinol Metab. 1998 Nov;83(11):4079-83. [Article]
  23. Wojcik J, Berg MA, Esposito N, Geffner ME, Sakati N, Reiter EO, Dower S, Francke U, Postel-Vinay MC, Finidori J: Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. J Clin Endocrinol Metab. 1998 Dec;83(12):4481-9. [Article]
  24. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [Article]
  25. Enberg B, Luthman H, Segnestam K, Ritzen EM, Sundstrom M, Norstedt G: Characterisation of novel missense mutations in the GH receptor gene causing severe growth retardation. Eur J Endocrinol. 2000 Jul;143(1):71-6. [Article]
  26. Takada D, Ezura Y, Ono S, Iino Y, Katayama Y, Xin Y, Wu LL, Larringa-Shum S, Stephenson SH, Hunt SC, Hopkins PN, Emi M: Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred. Am J Med Genet A. 2003 Aug 30;121A(2):136-40. [Article]
  27. Jorge AA, Souza SC, Arnhold IJ, Mendonca BB: The first homozygous mutation (S226I) in the highly-conserved WSXWS-like motif of the GH receptor causing Laron syndrome: supression of GH secretion by GnRH analogue therapy not restored by dihydrotestosterone administration. Clin Endocrinol (Oxf). 2004 Jan;60(1):36-40. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00052Somatotropinapproved, investigationalyesligandDetails
DB00082PegvisomantapprovedyesantagonistDetails
DB09098Somatremapproved, investigational, withdrawnyesagonistDetails
DB15093Somapacitanapproved, investigationalunknownagonistDetails
DB16220Lonapegsomatropinapproved, investigationalyesligandDetails