Parathyroid hormone 1 receptor

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Parathyroid hormone 1 receptor
PDB 1bl1 EBI.jpg
Rendering of 1BL1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PTH1R ; PFE; PTHR; PTHR1
External IDs OMIM168468 MGI97801 HomoloGene267 IUPHAR: 331 ChEMBL: 1793 GeneCards: PTH1R Gene
RNA expression pattern
PBB GE PTHR1 205911 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5745 19228
Ensembl ENSG00000160801 ENSMUSG00000032492
UniProt Q03431 P41593
RefSeq (mRNA) NM_000316 NM_001083935
RefSeq (protein) NP_000307 NP_001077404
Location (UCSC) Chr 3:
46.92 – 46.95 Mb
Chr 9:
110.72 – 110.74 Mb
PubMed search [1] [2]

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[edit]

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.[1][2] 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[edit]

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[edit]

Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC), chondrodysplasia Blomstrand type (BOCD), as well as enchondromatosis [3] and primary failure of tooth eruption. [4]

Interactions[edit]

Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2[5] and Sodium-hydrogen antiporter 3 regulator 1.[5]

Model organisms[edit]

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 [6]. Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12]




See also[edit]

References[edit]

  1. ^ Mannstadt M, Jüppner H, Gardella TJ (1999). "Receptors for PTH and PTHrP: their biological importance and functional properties". Am. J. Physiol. 277 (5 Pt 2): F665–75. PMID 10564229. 
  2. ^ Offermanns S, Iida-Klein A, Segre GV, Simon MI (1996). "G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells". Mol. Endocrinol. 10 (5): 566–74. doi:10.1210/me.10.5.566. PMID 8732687. 
  3. ^ "Entrez Gene: PTH1R parathyroid hormone 1 receptor". 
  4. ^ Yamaguchi, T; Hosomichi, K; Narita, A; Shirota, T; Tomoyasu, Y; Maki, K; Inoue, I (Mar 14, 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 : the official journal of the American Society for Bone and Mineral Research 26 (7): 1655–61. doi:10.1002/jbmr.385. PMID 21404329. 
  5. ^ a b Mahon, Matthew J; Donowitz Mark; Yun C Chris; Segre Gino V (Jun 2002). "Na(+)/H(+ ) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling". Nature (England) 417 (6891): 858–61. doi:10.1038/nature00816. ISSN 0028-0836. PMID 12075354. 
  6. ^ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Opthalmologica 88: 925-7.doi:10.1111/j.1755-3768.2010.4142.x: Wiley. 
  7. ^ a b "International Mouse Phenotyping Consortium". 
  8. ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (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 3572410. PMID 21677750. 
  9. ^ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  10. ^ 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. 
  11. ^ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN et al. (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. PMID 23870131. 
  12. ^ a b "Infection and Immunity Immunophenotyping (3i) Consortium". 

Further reading[edit]

External links[edit]

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