Parathyroid hormone 1 receptor

PTH1R
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1BL1, 3C4M, 3H3G, 3L2J, 4Z8J
Identifiers
Aliases	PTH1R, PFE, PTHR, PTHR1, Parathyroid hormone 1 receptor, EKNS
External IDs	OMIM: 168468 MGI: 97801 HomoloGene: 267 GeneCards: PTH1R
Gene location (Human)
Chr.	Chromosome 3 (human)[1]
End	46,903,799 bp[1]
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)[2]
End	110,747,145 bp[2]
RNA expression pattern
	Top expressed in
	kidney; ; tibia; ; right lobe of liver; ; periodontal fiber; ; metanephric glomerulus; ; right lung; ; kidney tubule; ; renal medulla; ; spleen; ; canal of the cervix;
	Top expressed in
	proximal tubule; ; kidney; ; body of femur; ; calvaria; ; clavicle; ; dermis; ; internal carotid artery; ; dermal bone; ; ankle; ; external carotid artery;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	G protein-coupled receptor activity; parathyroid hormone receptor activity; signal transducer activity; protein self-association; peptide hormone binding; protein binding; transmembrane signaling receptor activity; protein homodimerization activity; G protein-coupled peptide receptor activity;
Cellular component	cytoplasm; integral component of membrane; membrane; receptor complex; plasma membrane; intracellular anatomical structure; brush border membrane; basolateral plasma membrane; apical plasma membrane; nucleus; integral component of plasma membrane;
Biological process	skeletal system development; G protein-coupled receptor signaling pathway; bone mineralization; chondrocyte differentiation; ossification; positive regulation of inositol phosphate biosynthetic process; adenylate cyclase-modulating G protein-coupled receptor signaling pathway; positive regulation of cytosolic calcium ion concentration; G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; human ageing; cellular calcium ion homeostasis; cell maturation; bone resorption; phospholipase C-activating G protein-coupled receptor signaling pathway; cell surface receptor signaling pathway; positive regulation of cell population proliferation; osteoblast development; signal transduction; negative regulation of cell population proliferation; adenylate cyclase-activating G protein-coupled receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	5745
	19228
	ENSG00000160801
	ENSMUSG00000032492
	Q03431
	P41593
	NM_000316; NM_001184744
	NM_001083935; NM_001083936; NM_011199
	NP_000307; NP_001171673
	NP_001077404; NP_001077405; NP_035329
	Wikidata
View/Edit Human	View/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.[5][6] 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 G_s G proteins, which activate adenylyl cyclase. Besides this, they also activate the phosphatidylinositol-calcium second messenger system.

Pathology

Defects in this receptor are known to be the cause of Jansen's metaphyseal chondrodysplasia (JMC) and chondrodysplasia Blomstrand type (BOCD) as well as enchondromatosis[7] and primary failure of tooth eruption.[8]

Interactions

Parathyroid hormone 1 receptor has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2[9] and Sodium-hydrogen antiporter 3 regulator 1.[9]

Model organisms

Model organisms have been used in the study of PTH1R function. A conditional knockout mouse line called Pth1r^{tm1a(EUCOMM)Hmgu} was generated at the Wellcome Trust Sanger Institute.[10] Male and female animals underwent a standardized phenotypic screen[11] to determine the effects of deletion.[12][13][14][15] Additional screens performed: - In-depth immunological phenotyping[16]

*Pth1r* knockout mouse phenotype
Characteristic	Phenotype
All data available at.[11][16]
Peripheral blood leukocytes 6 Weeks	Normal
Insulin	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

References

GRCh38: Ensembl release 89: ENSG00000160801 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000032492 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. doi:10.1152/ajprenal.1999.277.5.F665. PMID 10564229. Archived from the original on 2009-02-13. Retrieved 2007-12-17.
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/mend.10.5.8732687. PMID 8732687.
"Entrez Gene: PTH1R parathyroid hormone 1 receptor".
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. S2CID 23855913.
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. S2CID 4379134.
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. S2CID 85911512.
"International Mouse Phenotyping Consortium".
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 3572410. PMID 21677750.
Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
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. S2CID 18872015.
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 3717207. PMID 23870131.
"Infection and Immunity Immunophenotyping (3i) Consortium".

External links

"Parathyroid Hormone Receptors: PTH1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Receptor,+Parathyroid+Hormone,+Type+1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160801 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032492 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10564229-5] 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. doi:10.1152/ajprenal.1999.277.5.F665. PMID 10564229. Archived from the original on 2009-02-13. Retrieved 2007-12-17.

[pmid8732687-6] 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/mend.10.5.8732687. PMID 8732687.

[entrez-7] "Entrez Gene: PTH1R parathyroid hormone 1 receptor".

[pmid21404329-8] 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. S2CID 23855913.

[pmid12075354-9] 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. S2CID 4379134.

[mgp_reference-10] 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. S2CID 85911512.

[IMPCsearch_ref-11] "International Mouse Phenotyping Consortium".

[pmid21677750-12] 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 3572410. PMID 21677750.

[mouse_library-13] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-14] 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. S2CID 18872015.

[pmid23870131-15] 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 3717207. PMID 23870131.

[iii_ref-16] "Infection and Immunity Immunophenotyping (3i) Consortium".