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.[1]
The molecular interaction of the PTH2 receptor with the peptideTIP39 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]
↑Weaver RE, Mobarec JC, Wigglesworth MJ, Reynolds CA, Donnelly D (2017). "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. doi:10.1016/j.bcp.2016.12.013.
Further reading
Usdin TB, Gruber C, Bonner TI (1995). "Identification and functional expression of a receptor selectively recognizing parathyroid hormone, the PTH2 receptor". J. Biol. Chem. 270 (26): 15455–8. doi:10.1074/jbc.270.26.15455. PMID7797535.
Usdin TB, Modi W, Bonner TI (1997). "Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization". Genomics. 37 (1): 140–1. doi:10.1006/geno.1996.0532. PMID8921382.
Clark JA, Bonner TI, Kim AS, Usdin TB (1998). "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. doi:10.1210/me.12.2.193. PMID9482662.
Hoare SR, Clark JA, Usdin TB (2000). "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. doi:10.1074/jbc.M003910200. PMID10854439.
John MR, Arai M, Rubin DA, et al. (2002). "Identification and characterization of the murine and human gene encoding the tuberoinfundibular peptide of 39 residues". Endocrinology. 143 (3): 1047–57. doi:10.1210/en.143.3.1047. PMID11861531.
Seeliger S, Hausberg M, Eue I, et al. (2003). "The parathyroid hormone-2 receptor is expressed on human leukocytes and down-regulated in hyperparathyroidism". Clin. Nephrol. 59 (6): 429–35. PMID12834174.
Bisello A, Manen D, Pierroz DD, et al. (2004). "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. doi:10.1210/me.2003-0487. PMID14988434.
Mahon MJ, Shimada M (2005). "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. doi:10.1016/j.febslet.2004.12.056. PMID15670850.
Weaver RE, Mobarec JC, Wigglesworth MJ, Reynolds CA, Donnelly D (2017). "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. doi:10.1016/j.bcp.2016.12.013.
