Parathyroid hormone 1 receptor

PTH1R
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases PTH1R, PFE, PTHR, PTHR1, Parathyroid hormone 1 receptor
External IDs MGI: 97801 HomoloGene: 267 GeneCards: PTH1R
Targeted by Drug
Teriparatide[1]
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

5745

19228

Ensembl

ENSG00000160801

ENSMUSG00000032492

UniProt

Q03431

P41593

RefSeq (mRNA)

NM_000316
NM_001184744

NM_001083935
NM_001083936
NM_011199

RefSeq (protein)

NP_000307.1
NP_001171673.1

NP_001077404.1
NP_001077405.1
NP_035329.2

Location (UCSC) Chr 3: 46.88 – 46.9 Mb Chr 9: 110.72 – 110.75 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/Edit Mouse

Parathyroid hormone/parathyroid hormone-related peptide receptor also known as parathyroid hormone 1 receptor (PTH1R) is a protein that in humans is encoded by the PTH1R gene. PTH1R functions as a receptor for parathyroid hormone (PTH) and for parathyroid hormone-related protein (PTHrP), also called parathyroid hormone-like hormone (PTHLH).

Function

This "classical" PTH receptor is expressed in high levels in bone and kidney and regulates calcium ion homeostasis through activation of adenylate cyclase and phospholipase C.[4][5] In bone, it is expressed on the surface of osteoblasts. When the receptor is activated through PTH binding, osteoblasts express RANKL (Receptor Activator of Nuclear Factor kB Ligand), which binds to RANK (Receptor Activator of Nuclear Factor kB) on osteoclasts. This turns on osteoclasts to ultimately increase the resorption rate.

Mechanism

It is a member of the secretin family of G protein-coupled receptors. The activity of this receptor is mediated by Gs G proteins which activate adenylyl cyclase. Besides, they also activate phosphatidylinositol-calcium second messenger system.

Pathology

Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchondromatosis [6] and primary failure of tooth eruption. [7]

Interactions

Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2[8] and Sodium-hydrogen antiporter 3 regulator 1.[8]

Model organisms

Model organisms have been used in the study of PTH1R function. A conditional knockout mouse line called Pth1rtm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15]


See also

References

  1. ↑ "Drugs that physically interact with Parathyroid hormone/parathyroid hormone-related peptide receptor view/edit references on wikidata".
  2. ↑ "Human PubMed Reference:".
  3. ↑ "Mouse PubMed Reference:".
  4. ↑ Mannstadt M, Jüppner H, Gardella TJ (Nov 1999). "Receptors for PTH and PTHrP: their biological importance and functional properties". The American Journal of Physiology. 277 (5 Pt 2): F665–75. PMID 10564229.
  5. ↑ Offermanns S, Iida-Klein A, Segre GV, Simon MI (May 1996). "G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells". Molecular Endocrinology. 10 (5): 566–74. doi:10.1210/me.10.5.566. PMID 8732687.
  6. ↑ "Entrez Gene: PTH1R parathyroid hormone 1 receptor".
  7. ↑ Yamaguchi T, Hosomichi K, Narita A, Shirota T, Tomoyasu Y, Maki K, Inoue I (Jul 2011). "Exome resequencing combined with linkage analysis identifies novel PTH1R variants in primary failure of tooth eruption in Japanese". Journal of Bone and Mineral Research. 26 (7): 1655–61. doi:10.1002/jbmr.385. PMID 21404329.
  8. 1 2 Mahon MJ, Donowitz M, Yun CC, Segre GV (Jun 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature. 417 (6891): 858–61. doi:10.1038/nature00816. PMID 12075354.
  9. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  10. 1 2 "International Mouse Phenotyping Consortium".
  11. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410Freely accessible. PMID 21677750.
  12. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  13. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  14. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207Freely accessible. PMID 23870131.
  15. 1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

  • Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE (Apr 2010). "Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation". The Journal of Biological Chemistry. 285 (16): 12435–44. doi:10.1074/jbc.M109.093138. PMID 20172855. 
  • Bonaventure J, Silve C (Nov 2005). "[Hereditary skeletal dysplasias and FGFR3 and PTHR1 signaling pathways]". Médecine Sciences. 21 (11): 954–61. doi:10.1051/medsci/20052111954. PMID 16274647. 
  • Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–20. doi:10.1016/S0163-4453(05)80037-4. PMID 1602151. 
  • Schipani E, Kruse K, Jüppner H (Apr 1995). "A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia". Science. 268 (5207): 98–100. doi:10.1126/science.7701349. PMID 7701349. 
  • Schipani E, Weinstein LS, Bergwitz C, Iida-Klein A, Kong XF, Stuhrmann M, Kruse K, Whyte MP, Murray T, Schmidtke J (May 1995). "Pseudohypoparathyroidism type Ib is not caused by mutations in the coding exons of the human parathyroid hormone (PTH)/PTH-related peptide receptor gene". The Journal of Clinical Endocrinology and Metabolism. 80 (5): 1611–21. doi:10.1210/jc.80.5.1611. PMID 7745008. 
  • Pausova Z, Bourdon J, Clayton D, Mattei MG, Seldin MF, Janicic N, Rivière M, Szpirer J, Levan G, Szpirer C (Mar 1994). "Cloning of a parathyroid hormone/parathyroid hormone-related peptide receptor (PTHR) cDNA from a rat osteosarcoma (UMR 106) cell line: chromosomal assignment of the gene in the human, mouse, and rat genomes". Genomics. 20 (1): 20–6. doi:10.1006/geno.1994.1122. PMID 8020952. 
  • McCuaig KA, Clarke JC, White JH (May 1994). "Molecular cloning of the gene encoding the mouse parathyroid hormone/parathyroid hormone-related peptide receptor". Proceedings of the National Academy of Sciences of the United States of America. 91 (11): 5051–5. doi:10.1073/pnas.91.11.5051. PMC 43929Freely accessible. PMID 8197183. 
  • Schipani E, Karga H, Karaplis AC, Potts JT, Kronenberg HM, Segre GV, Abou-Samra AB, Jüppner H (May 1993). "Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor". Endocrinology. 132 (5): 2157–65. doi:10.1210/en.132.5.2157. PMID 8386612. 
  • Schneider H, Feyen JH, Seuwen K, Movva NR (Jul 1993). "Cloning and functional expression of a human parathyroid hormone receptor". European Journal of Pharmacology. 246 (2): 149–55. doi:10.1016/0922-4106(93)90092-N. PMID 8397094. 
  • Schipani E, Langman CB, Parfitt AM, Jensen GS, Kikuchi S, Kooh SW, Cole WG, Jüppner H (Sep 1996). "Constitutively activated receptors for parathyroid hormone and parathyroid hormone-related peptide in Jansen's metaphyseal chondrodysplasia". The New England Journal of Medicine. 335 (10): 708–14. doi:10.1056/NEJM199609053351004. PMID 8703170. 
  • Zhou AT, Bessalle R, Bisello A, Nakamoto C, Rosenblatt M, Suva LJ, Chorev M (Apr 1997). "Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking". Proceedings of the National Academy of Sciences of the United States of America. 94 (8): 3644–9. doi:10.1073/pnas.94.8.3644. PMC 20494Freely accessible. PMID 9108031. 
  • Schipani E, Jensen GS, Pincus J, Nissenson RA, Gardella TJ, Jüppner H (Jun 1997). "Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia". Molecular Endocrinology. 11 (7): 851–8. doi:10.1210/me.11.7.851. PMID 9178745. 
  • Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C (Jul 1998). "Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia". The Journal of Clinical Investigation. 102 (1): 34–40. doi:10.1172/JCI2918. PMC 509062Freely accessible. PMID 9649554. 
  • Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF (Sep 1998). "Binding domain of human parathyroid hormone receptor: from conformation to function". Biochemistry. 37 (37): 12737–43. doi:10.1021/bi981265h. PMID 9737850. 
  • Zhang P, Jobert AS, Couvineau A, Silve C (Sep 1998). "A homozygous inactivating mutation in the parathyroid hormone/parathyroid hormone-related peptide receptor causing Blomstrand chondrodysplasia". The Journal of Clinical Endocrinology and Metabolism. 83 (9): 3365–8. doi:10.1210/jc.83.9.3373. PMID 9745456. 
  • Adams AE, Bisello A, Chorev M, Rosenblatt M, Suva LJ (Nov 1998). "Arginine 186 in the extracellular N-terminal region of the human parathyroid hormone 1 receptor is essential for contact with position 13 of the hormone". Molecular Endocrinology. 12 (11): 1673–83. doi:10.1210/me.12.11.1673. PMID 9817594. 
  • Matsuzaki K, Katayama K, Takahashi Y, Nakamura I, Udagawa N, Tsurukai T, Nishinakamura R, Toyama Y, Yabe Y, Hori M, Takahashi N, Suda T (Feb 1999). "Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene". Endocrinology. 140 (2): 925–32. doi:10.1210/en.140.2.925. PMID 9927325. 
  • Schipani E, Langman C, Hunzelman J, Le Merrer M, Loke KY, Dillon MJ, Silve C, Jüppner H (Sep 1999). "A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia". The Journal of Clinical Endocrinology and Metabolism. 84 (9): 3052–7. doi:10.1210/jc.84.9.3052. PMID 10487664. 
  • Karperien M, van der Harten HJ, van Schooten R, Farih-Sips H, den Hollander NS, Kneppers SL, Nijweide P, Papapoulos SE, Löwik CW (Oct 1999). "A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia". The Journal of Clinical Endocrinology and Metabolism. 84 (10): 3713–20. doi:10.1210/jc.84.10.3713. PMID 10523019. 
  • Watson PH, Fraher LJ, Natale BV, Kisiel M, Hendy GN, Hodsman AB (Mar 2000). "Nuclear localization of the type 1 parathyroid hormone/parathyroid hormone-related peptide receptor in MC3T3-E1 cells: association with serum-induced cell proliferation". Bone. 26 (3): 221–5. doi:10.1016/S8756-3282(99)00264-1. PMID 10709993. 
  • Truneh A, Sharma S, Silverman C, Khandekar S, Reddy MP, Deen KC, McLaughlin MM, Srinivasula SM, Livi GP, Marshall LA, Alnemri ES, Williams WV, Doyle ML (Jul 2000). "Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor". The Journal of Biological Chemistry. 275 (30): 23319–25. doi:10.1074/jbc.M910438199. PMID 10770955. 

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