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PTH2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 332

Nomenclature: PTH2 receptor

Family: Parathyroid hormone receptors

Contents:

Gene and Protein Information Click here for help
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 550 2q34 PTH2R parathyroid hormone 2 receptor 28,31
Mouse 7 546 1 33.05 cM Pth2r parathyroid hormone 2 receptor
Rat 7 546 9q32 Pth2r parathyroid hormone 2 receptor 27
Previous and Unofficial Names Click here for help
PTHR2
Database Links Click here for help
Specialist databases
GPCRdb pth2r_human (Hs), pth2r_mouse (Mm)
Other databases
Alphafold P49190 (Hs), Q91V95 (Mm), P70555 (Rn)
CATH/Gene3D 4.10.1240.10
ChEMBL Target CHEMBL4105836 (Hs)
DrugBank Target P49190 (Hs)
Ensembl Gene ENSG00000144407 (Hs), ENSMUSG00000025946 (Mm), ENSRNOG00000015259 (Rn)
Entrez Gene 5746 (Hs), 213527 (Mm), 81753 (Rn)
Human Protein Atlas ENSG00000144407 (Hs)
KEGG Gene hsa:5746 (Hs), mmu:213527 (Mm), rno:81753 (Rn)
OMIM 601469 (Hs)
Pharos P49190 (Hs)
RefSeq Nucleotide NM_005048 (Hs), NM_139270 (Mm), NM_031089 (Rn)
RefSeq Protein NP_005039 (Hs), NP_644676 (Mm), NP_112351 (Rn)
UniProtKB P49190 (Hs), Q91V95 (Mm), P70555 (Rn)
Wikipedia PTH2R (Hs)
Natural/Endogenous Ligands Click here for help
PTH {Sp: Human} , PTH {Sp: Mouse} , PTH {Sp: Rat}
PTHrP-(1-36) {Sp: Human}
PTHrP-(1-34) (human)
TIP39 {Sp: Human, Bovine} , TIP39 {Sp: Mouse, Rat}
Comments: PTH is a weak partial agonist in rat. PTHrP has very low efficacy. Other endogenous fragments of parathyroid hormone-related protein precursor are PTHrP-(107-139) (human)/PTHrP-(107-139) (mouse)/PTHrP-(107-139) (rat) and PTHrP-(38-94).
Potency order of endogenous ligands (Human)
TIP39 (PTH2, Q96A98), PTH (PTH, P01270) >> PTHrP (PTHLH, P12272)

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I][Nle8,21,Tyr34]PTH-(1-34)-NH2 (rat) Peptide Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 8.1 pKd 3
⤷ pKd 8.1 [3]
TIP39 {Sp: Mouse, Rat} Peptide Hs Full agonist 8.8 pIC50 17
⤷ pIC50 8.8 [17]
TIP39 {Sp: Human, Bovine} Peptide Click here for species-specific activity table Hs Full agonist 7.6 – 9.2 pIC50 17,19
⤷ pIC50 7.6 – 9.2 [17,19]
PTH-(1-34) (rat) Peptide Click here for species-specific activity table Hs Full agonist 7.2 – 9.5 pIC50 4,17,19
⤷ pIC50 7.2 – 9.5 [4,17,19]
TIP39 {Sp: Mouse, Rat} Peptide Ligand is endogenous in the given species Rn Full agonist 8.1 pIC50 17
⤷ pIC50 8.1 [17]
teriparatide Peptide Approved drug Click here for species-specific activity table Hs Full agonist 7.7 – 7.8 pIC50 16-17
⤷ pIC50 7.7 – 7.8 [16-17]
[Ile5,Trp23,Tyr36]PTHrP-(1-36)-NH2 (human) Peptide Click here for species-specific activity table Hs Full agonist 7.7 pIC50 3
⤷ pIC50 7.7 [3]
[Ile5,Trp23]PTHrP-(1-36) (human) Peptide Click here for species-specific activity table Hs Full agonist 7.1 – 8.0 pIC50 4,16
⤷ pIC50 7.1 – 8.0 [4,16]
[Trp23]PTHrP-(1-36) (human) Peptide Click here for species-specific activity table Hs Full agonist 7.5 pIC50 16
⤷ pIC50 7.5 [16]
[Trp23,Tyr36]PTHrP-(1-36)-NH2 (human) Peptide Click here for species-specific activity table Hs Full agonist 7.4 pIC50 3
⤷ pIC50 7.4 [3]
[Ile5,Trp23]PTHrP-(2-36) (human) Peptide Click here for species-specific activity table Hs Full agonist 7.3 pIC50 4
⤷ pIC50 7.3 [4]
[Ile5,Trp23]PTHrP-(3-36) (human) Peptide Click here for species-specific activity table Hs Full agonist 7.2 pIC50 4
⤷ pIC50 7.2 [4]
TIP39 {Sp: Human, Bovine} Peptide Rn Full agonist 7.0 pIC50 17
⤷ pIC50 7.0 [17]
[Ile5,Trp23]PTHrP-(5-36) (human) Peptide Hs Full agonist 7.0 pIC50 4
⤷ pIC50 7.0 [4]
[Ile5,Trp23]PTHrP-(4-36) (human) Peptide Click here for species-specific activity table Hs Full agonist 6.8 pIC50 4
⤷ pIC50 6.8 [4]
PTH-(1-34) (rat) Peptide Rn Full agonist 6.8 pIC50 17
⤷ pIC50 6.8 [17]
[His5]PTH-(1-34) (human) Peptide Click here for species-specific activity table Hs Full agonist 6.6 pIC50 16
⤷ pIC50 6.6 [16]
[Phe23]PTH-(1-34) (human) Peptide Click here for species-specific activity table Hs Full agonist 6.3 pIC50 16
⤷ pIC50 6.3 [16]
teriparatide Peptide Approved drug Click here for species-specific activity table Rn Full agonist 6.3 pIC50 17
⤷ pIC50 6.3 [17]
[Ile5]PTHrP-(1-36) Peptide Hs Full agonist 6.2 pIC50 17
⤷ pIC50 6.2 [17]
PTHrP-(1-34) (human) Peptide Ligand is endogenous in the given species Hs Full agonist 6.1 pIC50 17
⤷ pIC50 6.1 [17]
PTHrP-(1-36) {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 5.7 pIC50 16
⤷ pIC50 5.7 [16]
PTHrP-(1-34) (human) Peptide Click here for species-specific activity table Ligand is endogenous in the given species Rn Full agonist 5.3 pIC50 17
⤷ pIC50 5.3 [17]
View species-specific agonist tables
Agonist Comments
The species of peptide ligand is stated in parentheses. This can include synthetic peptides made based on the sequence of the stated species.

The amino acide sequences of human and bovine TIP39 are identical. Mouse TIP39 differs in four positions at the carboxyl-terminal of the polypeptide.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[His4, Tyr5, Trp6, His7]TIP39 (human) Peptide Rn Antagonist 7.6 pA2
⤷ pA2 7.6
TIP39-(7-39) (mouse) Peptide Hs Antagonist 8.2 pIC50 17
⤷ pIC50 8.2 [17]
PTHrP-(1-21)/PTH-(22-34) (human) Peptide Click here for species-specific activity table Hs Antagonist 7.0 – 8.0 pIC50 16-17
⤷ pIC50 7.0 – 8.0 [16-17]
[D-Trp12]PTH-(7-34) (bovine) Peptide Hs Antagonist 7.3 pIC50 17
⤷ pIC50 7.3 [17]
TIP39-(7-39) (human/bovine) Peptide Click here for species-specific activity table Hs Antagonist 7.0 – 7.2 pIC50 17,20
⤷ pIC50 7.0 – 7.2 [17,20]
[Ile5,Trp23]PTHrP-(5-36) Peptide Click here for species-specific activity table Hs Antagonist 7.0 pIC50 4
⤷ pIC50 7.0 [4]
[D-Trp12,Tyr34]PTH-(7-34) (bovine) Peptide Click here for species-specific activity table Hs Antagonist 6.9 pIC50 20
⤷ pIC50 6.9 [20]
PTHrP-(7-34) (human, rat, mouse) Peptide Click here for species-specific activity table Hs Antagonist 6.7 pIC50 20
⤷ pIC50 6.7 [20]
TIP39-(7-39) (mouse) Peptide Rn Antagonist 6.5 pIC50 17
⤷ pIC50 6.5 [17]
[D-Trp12]PTH-(7-34) (bovine) Peptide Rn Antagonist 6.3 pIC50 17
⤷ pIC50 6.3 [17]
TIP39-(7-39) (human/bovine) Peptide Rn Antagonist 6.1 pIC50 17
⤷ pIC50 6.1 [17]
PTHrP-(1-21)/PTH-(22-34) (human) Peptide Rn Antagonist 5.5 pIC50 17
⤷ pIC50 5.5 [17]
View species-specific antagonist tables
Antagonist Comments
The species of peptide ligand is stated in parentheses. This can include synthetic peptides made based on the sequence of the stated species.
Tissue Distribution Click here for help
Brain: medial prefrontal, insular, and ectorhinal cortices, lateral septal nucleus, bed nucleus of the stria terminalis, fundus striati, amygdala, ventral subiculum, hypothalamus, midline and intralaminar thalamic nuclei, medial geniculate body, periaqueductal gray, ventral tegmental area, superior and inferior colliculi, parabrachial nuclei, locus coeruleus, subcoeruleus and periolivary areas, nucleus of the solitary tract.
Species:  Mouse
Technique:  In situ hybridisation and immunohistochemistry.
References:  14
Pancreas (somatostatin-producing pancreatic islets), thyroid gland (parafollicular cells), gastrointestinal tract (peptide-producing cells in the gastric epithelium, parasympathetic ganglion cells in the submucosal and myenteric plexuses), cardiovascular system (vascular endothelium and smooth muscle), chondrocytes in tracheal cartilage, kidney (near the vascular pole of glomeruli), brain, adrenal medulla, zona glomerulosa of the adrenal cortex, parathyroid gland, pulmonary bronchioles.
Species:  Rat
Technique:  in situ hybridisation.
References:  27
Thyroid parafollicular cells, pancreatic islet D cells, some gastrointestinal peptide synthesising cells.
Species:  Rat
Technique:  Immunohistochemistry.
References:  29
CNS: cerebral cortex, striatum, septum, midline thalamic nuclei, hypothalamus (periventricular and arcuate nuclei), external zone of the median eminence, superficial layers of the caudal spinal trigeminal tract, spinal cord dorsal horn.
Species:  Rat
Technique:  In situ hybridisation and immunohistochemistry.
References:  11,32
CNS: spinal cord and dorsal root ganglia.
Species:  Rat
Technique:  in situ hybridisation.
References:  12
Renal vessels, aorta.
Species:  Rat
Technique:  RT-PCR.
References:  13
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in F-11 cells (a fusion of rat DRG neurons expressing the PTH2 receptor and a mouse neuroblastoma cell line).
Species:  Rat
Tissue:  F-11 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  30
Measurement of cAMP levels in COS-7 cells transfected with the human PTH2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  5,18,28,30
Measurement of cAMP levels in COS-7 cells transfected with the rat PTH2 receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  18,30
Measurement of cAMP levels in HEK 293 cells transfected with the human PTH2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Stimulation of cAMP accumulation.
References:  1-2,19,23,26
Measurement of Ca2+ levels in HEK 293 cells transfected with the PTH2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in intracellular Ca2+ concentration.
References:  1-2
Measurement of cell proliferation in HEK 293 cells transfected with the human PTH2 receptor, using an ATP bioluminescence assay.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cell proliferation.
References:  23
Measurement of Ca2+ levels in COS-7 cells transfected with the human PTH2 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Stimulation of Ca2+ mobilisation.
References:  17
Measurement of Ca2+ levels in COS-7 cells transfected with the rat PTH2 receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Stimulation of Ca2+ mobilisation.
References:  17
Physiological Functions Click here for help
Stimulation of hypothalamic releasing factor secretion
Species:  Rat
Tissue:  Hypothalamic explants
References:  33
Positive inotropy
Species:  Rat
Tissue:  Isolated heart
References:  21
Modulation of nociceptive transmission in the spinal cord
Species:  Mouse
Tissue:  in vivo
References:  12
Supraspinal modulation of nociception
Species:  Mouse
Tissue:  in vivo
References:  10
Modulation of Hypothalamo-Pituitary Adrenal Axis
Species:  Mouse
Tissue:  in vivo
References:  8
Stressor-dependent modulation of anxiety-like behavior and memory performance
Species:  Mouse
Tissue:  in vivo
References:  6,15
Modulation of prolactin section by lactating dams
Species:  Rat
Tissue:  in vivo
References:  7
Facilitation of thermal response to cold exposure
Species:  Mouse
Tissue:  in vivo
References:  9
Supression of arginine vasopressin release
Species:  Rat
Tissue:  in vivo
References:  25
Modulation of renal vessel tone
Species:  Rat
Tissue:  Isolated renal vessels
References:  13
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A Ala225 -> Ser polymorphism may be linked to osteoarthritis.
Amino acid change:  A225S
References:  22
General Comments
See [24] for a study describing the molecular modelling of the interaction between PTH and the PTH1 and PTH2 receptors.

References

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1. Behar V, Nakamoto C, Greenberg Z, Bisello A, Suva LJ, Rosenblatt M, Chorev M. (1996) Histidine at position 5 is the specificity "switch" between two parathyroid hormone receptor subtypes. Endocrinology, 137 (10): 4217-24. [PMID:8828480]

2. Behar V, Pines M, Nakamoto C, Greenberg Z, Bisello A, Stueckle SM, Bessalle R, Usdin TB, Chorev M, Rosenblatt M, Suva LJ. (1996) The human PTH2 receptor: binding and signal transduction properties of the stably expressed recombinant receptor. Endocrinology, 137: 2748-2757. [PMID:8770894]

3. Bergwitz C, Jusseaume SA, Luck MD, Jüppner H, Gardella TJ. (1997) Residues in the membrane-spanning and extracellular loop regions of the parathyroid hormone (PTH)-2 receptor determine signaling selectivity for PTH and PTH-related peptide. J Biol Chem, 272 (46): 28861-8. [PMID:9360953]

4. Carter PH, Jüppner H, Gardella TJ. (1999) Studies of the N-terminal region of a parathyroid hormone-related peptide (1-36) analog: receptor subtype-selective agonists, antagonists, and photochemical cross-linking agents. Endocrinology, 140 (11): 4972-81. [PMID:10537121]

5. 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. [PMID:9482662]

6. Coutellier L, Logemann A, Kuo J, Rusnak M, Usdin TB. (2011) TIP39 modulates effects of novelty-induced arousal on memory. Genes Brain Behav, 10 (1): 90-9. [PMID:20796031]

7. Cservenák M, Bodnár I, Usdin TB, Palkovits M, Nagy GM, Dobolyi A. (2010) Tuberoinfundibular peptide of 39 residues is activated during lactation and participates in the suckling-induced prolactin release in rat. Endocrinology, 151 (12): 5830-40. [PMID:20861230]

8. Dimitrov E, Usdin TB. (2010) Tuberoinfundibular peptide of 39 residues modulates the mouse hypothalamic-pituitary-adrenal axis via paraventricular glutamatergic neurons. J Comp Neurol, 518 (21): 4375-94. [PMID:20853513]

9. Dimitrov EL, Kim YY, Usdin TB. (2011) Regulation of hypothalamic signaling by tuberoinfundibular peptide of 39 residues is critical for the response to cold: a novel peptidergic mechanism of thermoregulation. J Neurosci, 31 (49): 18166-79. [PMID:22159128]

10. Dimitrov EL, Petrus E, Usdin TB. (2010) Tuberoinfundibular peptide of 39 residues (TIP39) signaling modulates acute and tonic nociception. Exp Neurol, 226 (1): 68-83. [PMID:20696160]

11. Dobolyi A, Irwin S, Wang J, Usdin TB. (2006) The distribution and neurochemistry of the parathyroid hormone 2 receptor in the rat hypothalamus. Neurochem Res, 31 (2): 227-36. [PMID:16570212]

12. Dobolyi A, Ueda H, Uchida H, Palkovits M, Usdin TB. (2002) Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception. Proc Natl Acad Sci USA, 99 (3): 1651-6. [PMID:11818570]

13. Eichinger A, Fiaschi-Taesch N, Massfelder T, Fritsch S, Barthelmebs M, Helwig JJ. (2002) Transcript expression of the tuberoinfundibular peptide (TIP)39/PTH2 receptor system and non-PTH1 receptor-mediated tonic effects of TIP39 and other PTH2 receptor ligands in renal vessels. Endocrinology, 143 (8): 3036-43. [PMID:12130570]

14. Faber CA, Dobolyi A, Sleeman M, Usdin TB. (2007) Distribution of tuberoinfundibular peptide of 39 residues and its receptor, parathyroid hormone 2 receptor, in the mouse brain. J Comp Neurol, 502 (4): 563-83. [PMID:17394159]

15. Fegley DB, Holmes A, Riordan T, Faber CA, Weiss JR, Ma S, Batkai S, Pacher P, Dobolyi A, Murphy A et al.. (2008) Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues. Genes Brain Behav, 7 (8): 933-42. [PMID:18700839]

16. Gardella TJ, Luck MD, Jensen GS, Usdin TB, Jüppner H. (1996) Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-2 receptor agonist. J Biol Chem, 271 (33): 19888-93. [PMID:8702701]

17. Goold CP, Usdin TB, Hoare SR. (2001) Regions in rat and human parathyroid hormone (PTH) 2 receptors controlling receptor interaction with PTH and with antagonist ligands. J Pharmacol Exp Ther, 299 (2): 678-90. [PMID:11602681]

18. Hoare SR, Bonner TI, Usdin TB. (1999) Comparison of rat and human parathyroid hormone 2 (PTH2) receptor activation: PTH is a low potency partial agonist at the rat PTH2 receptor. Endocrinology, 140: 4419-4425. [PMID:10499494]

19. 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. [PMID:10854439]

20. Hoare SR, Usdin TB. (2000) Tuberoinfundibular peptide (7-39) [TIP(7-39)], a novel, selective, high-affinity antagonist for the parathyroid hormone-1 receptor with no detectable agonist activity. J Pharmacol Exp Ther, 295 (2): 761-70. [PMID:11046116]

21. LaBuda CJ, Dobolyi A, Usdin TB. (2004) Tuberoinfundibular peptide of 39 residues produces anxiolytic and antidepressant actions. Neuroreport, 15 (5): 881-5. [PMID:15073536]

22. Meulenbelt I, Min JL, van Duijn CM, Kloppenburg M, Breedveld FC, Slagboom PE. (2006) Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes. Eur J Hum Genet, 14 (12): 1280-7. [PMID:16912703]

23. Misiano P, Scott BB, Scheideler MA, Garnier M. (2003) PTH2 receptor-mediated inhibitory effect of parathyroid hormone and TIP39 on cell proliferation. Eur J Pharmacol, 468 (3): 159-66. [PMID:12754053]

24. Rölz C, Pellegrini M, Mierke DF. (1999) Molecular characterization of the receptor-ligand complex for parathyroid hormone. Biochemistry, 38 (20): 6397-405. [PMID:10350457]

25. Sugimura Y, Murase T, Ishizaki S, Tachikawa K, Arima H, Miura Y, Usdin TB, Oiso Y. (2003) Centrally administered tuberoinfundibular peptide of 39 residues inhibits arginine vasopressin release in conscious rats. Endocrinology, 144 (7): 2791-6. [PMID:12810532]

26. Turner PR, Mefford S, Bambino T, Nissenson RA. (1998) Transmembrane residues together with the amino terminus limit the response of the parathyroid hormone (PTH) 2 receptor to PTH-related peptide. J Biol Chem, 273: 3830-3837. [PMID:9461563]

27. Usdin TB, Bonner TI, Harta G, Mezey E. (1996) Distribution of parathyroid hormone-2 receptor messenger ribonucleic acid in rat. Endocrinology, 137 (10): 4285-97. [PMID:8828488]

28. 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. [PMID:7797535]

29. Usdin TB, Hilton J, Vertesi T, Harta G, Segre G, Mezey E. (1999) Distribution of the parathyroid hormone 2 receptor in rat: immunolocalization reveals expression by several endocrine cells. Endocrinology, 140: 3363-3371. [PMID:10385434]

30. Usdin TB, Hoare SR, Wang T, Mezey E, Kowalak JA. (1999) TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Nat Neurosci, 2 (11): 941-3. [PMID:10526330]

31. Usdin TB, Modi W, Bonner TI. (1996) Assignment of the human PTH2 receptor gene (PTHR2) to chromosome 2q33 by fluorescence in situ hybridization. Genomics, 37 (1): 140-1. [PMID:8921382]

32. Wang T, Palkovits M, Rusnak M, Mezey E, Usdin TB. (2000) Distribution of parathyroid hormone-2 receptor-like immunoreactivity and messenger RNA in the rat nervous system. Neuroscience, 100 (3): 629-49. [PMID:11098126]

33. Ward HL, Small CJ, Murphy KG, Kennedy AR, Ghatei MA, Bloom SR. (2001) The actions of tuberoinfundibular peptide on the hypothalamo-pituitary axes. Endocrinology, 142 (8): 3451-6. [PMID:11459790]

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