Parathyroid hormone 2 receptor explained

Parathyroid hormone 2 receptor is a protein that in humans is encoded by the PTH2R gene.^[1]

Function

The protein encoded by this gene is a member of the G protein-coupled receptor family 2. This protein is a receptor for parathyroid hormone (PTH). This receptor is more selective in ligand recognition and has a more specific tissue distribution compared to parathyroid hormone 1 receptor (PTH1R). It is activated by PTH but not by parathyroid hormone-like hormone (PTHLH) and is particularly abundant in the brain and pancreas.

The molecular interaction of the PTH2 receptor with the peptide TIP39 has been characterized in full 3D molecular detail, identifying among other residues Tyr-318 in transmembrane helix 5 as a key residue for high affinity binding.^[2]

Mechanism

It is a member of the secretin family of G protein-coupled receptors. The activity of this receptor is mediated by G_s protein, which activates adenylyl cyclase.^[3]

See also

• Parathyroid hormone receptor

Further reading

• Usdin TB, Gruber C, Bonner TI . Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor. . J. Biol. Chem. . 270 . 26 . 15455–8 . 1995 . 7797535 . 10.1074/jbc.270.26.15455 . free .
• Usdin TB, Modi W, Bonner TI . Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. . Genomics . 37 . 1 . 140–1 . 1997 . 8921382 . 10.1006/geno.1996.0532 .
• Clark JA, Bonner TI, Kim AS, Usdin TB . Multiple regions of ligand discrimination revealed by analysis of chimeric parathyroid hormone 2 (PTH2) and PTH/PTH-related peptide (PTHrP) receptors. . Mol. Endocrinol. . 12 . 2 . 193–206 . 1998 . 9482662 . 10.1210/mend.12.2.0063 . free .
• Hoare SR, Clark JA, Usdin TB . Molecular determinants of tuberoinfundibular peptide of 39 residues (TIP39) selectivity for the parathyroid hormone-2 (PTH2) receptor. N-terminal truncation of TIP39 reverses PTH2 receptor/PTH1 receptor binding selectivity. . J. Biol. Chem. . 275 . 35 . 27274–83 . 2000 . 10854439 . 10.1074/jbc.M003910200 . free .
• John MR, Arai M, Rubin DA, etal . Identification and characterization of the murine and human gene encoding the tuberoinfundibular peptide of 39 residues. . Endocrinology . 143 . 3 . 1047–57 . 2002 . 11861531 . 10.1210/endo.143.3.8698 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Seeliger S, Hausberg M, Eue I, etal . The parathyroid hormone-2 receptor is expressed on human leukocytes and down-regulated in hyperparathyroidism. . Clin. Nephrol. . 59 . 6 . 429–35 . 2003 . 12834174 . 10.5414/CNP59429.
• Bisello A, Manen D, Pierroz DD, etal . Agonist-specific regulation of parathyroid hormone (PTH) receptor type 2 activity: structural and functional analysis of PTH- and tuberoinfundibular peptide (TIP) 39-stimulated desensitization and internalization. . Mol. Endocrinol. . 18 . 6 . 1486–98 . 2004 . 14988434 . 10.1210/me.2003-0487 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928.
• Mahon MJ, Shimada M . Calmodulin interacts with the cytoplasmic tails of the parathyroid hormone 1 receptor and a sub-set of class b G-protein coupled receptors. . FEBS Lett. . 579 . 3 . 803–7 . 2005 . 15670850 . 10.1016/j.febslet.2004.12.056 . 6471940 . free . 2005FEBSL.579..803M .
• Weaver RE, Mobarec JC, Wigglesworth MJ, Reynolds CA, Donnelly D . High affinity binding of the peptide agonist TIP-39 to the Parathyroid hormone 2 (PTH2) receptor requires the hydroxyl group of Tyr-318 on transmembrane helix 5. . Biochemical Pharmacology . 127. 71–81. 2017 . 28012961. 5303546 . 10.1016/j.bcp.2016.12.013 .

External links

• Web site: Parathyroid Hormone Receptors: PTH2 . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-09 . 2016-03-03 . https://web.archive.org/web/20160303192534/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2970 . dead .

Notes and References

1. Web site: Entrez Gene: PTH2R parathyroid hormone 2 receptor .
2. Weaver RE, Mobarec JC, Wigglesworth MJ, Reynolds CA, Donnelly D . High affinity binding of the peptide agonist TIP-39 to the Parathyroid hormone 2 (PTH2) receptor requires the hydroxyl group of Tyr-318 on transmembrane helix 5. . Biochemical Pharmacology . 127. 71–81. 2017 . 28012961. 5303546 . 10.1016/j.bcp.2016.12.013 .
3. Dobolyi . Arpad . Dimitrov . Eugene . Palkovits . Miklos . Usdin . Ted B. . The neuroendocrine functions of the parathyroid hormone 2 receptor . Frontiers in Endocrinology . 3 . 121 . 10.3389/fendo.2012.00121 . 2012. free . 23060860 . 3465808 .