Tuberoinfundibular peptide of 39 residues

experimental

Also known as: Parathyroid hormone 2, PTH2, Q96A98

Tuberoinfundibular peptide of 39 residues (TIP39), also known as parathyroid hormone 2 (PTH2), is a neuropeptide that acts as a potent and selective agonist for the parathyroid hormone 2 receptor (PTH2R). Its primary mechanism involves binding to PTH2R, which is a G protein-coupled receptor, leading to activation of adenyl cyclase and subsequent elevation of intracellular cyclic AMP levels. Additionally, TIP39 signaling can increase intracellular calcium concentrations, likely through downstream pathways involving phospholipase C. This dual signaling distinguishes TIP39 from parathyroid hormone (PTH), which primarily activates PTH1R. Research on TIP39 remains at an experimental stage, with limited PubMed-indexed studies (3 references). Key findings indicate that TIP39 is predominantly expressed in the central nervous system, particularly in regions such as the hypothalamus and brainstem, suggesting roles in neuroendocrine regulation and pain modulation. Preclinical studies have implicated TIP39 in stress responses, thermoregulation, and nociception, though its precise physiological functions are not fully characterized. The peptide's selective activation of PTH2R, which has a distinct tissue distribution from PTH1R, highlights its potential as a tool for dissecting PTH receptor signaling pathways. Clinically, TIP39 has no established therapeutic applications, and its relevance is confined to basic research. The limited number of studies and experimental status preclude any translational conclusions. Further investigation is needed to clarify its role in human physiology and disease, particularly in neurological or endocrine contexts. For research purposes only — not medical advice.

Key data

Category
Cognitive & Neuroprotective
Sequence
METRQVSRSPRVRLLLLLLLLLVVPWGVRTASGVALPPVGVLSLRPPGRAWADPATPRPRRSLALADDAAFRERARLLAALERRHWLNSYMHKLLVLDAP
Molecular weight
11202 g/mol
Research status
experimental
References
3
Tags
uniprot, 3d-structure, cleavage-on-pair-of-basic-residues, neuropeptide, proteomics-identification, reference-proteome, secreted, signal

Mechanism of action

Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation. Induces protein kinase C beta activation, recruitment of beta-arrestin and PTH2R internalization. May inhibit cell proliferation via its action on PTH2R activation. Neuropeptide which may also have a role in spermatogenesis. May activate nociceptors and nociceptive circuits

Research & studies

Neuropeptide TIP39 as a pluripotent brain molecule and its potential functions in postpartum depression
Frontiers in endocrinology · 2026 · PubMed

TIP39 is a small peptide from the PTH-related family that specifically binds PTH2R and regulates mood, maternal behavior, and social functions.; The review hypothesizes TIP39 as a common pathway linking depressive mood and maternal behavior deficits in PPD.; TIP39's multifunctional nature suggests it could be a promising therapeutic target for PPD treatment.

The parathyroid hormone 2 receptor participates in physiological and behavioral alterations of mother mice
Physiology & behavior · 2017 · PubMed
Enhanced long-term fear memory and increased anxiety and depression-like behavior after exposure to an aversive event in mice lacking TIP39 signaling
Behavioural brain research · 2011 · PubMed

Mice lacking TIP39 signaling show enhanced fear recall after a traumatic event.; These mice also display increased anxiety and depression-like behavior two weeks later.; TIP39 is suggested to modulate long-term fear memory and limit consequences of aversive experiences.

Frequently asked questions

What is Tuberoinfundibular peptide of 39 residues?

Tuberoinfundibular peptide of 39 residues (TIP39), also known as parathyroid hormone 2 (PTH2), is a neuropeptide that acts as a potent and selective agonist for the parathyroid hormone 2 receptor (PTH2R). Its primary mechanism involves binding to PTH2R, which is a G protein-coupled receptor, leading to activation of ad

How does Tuberoinfundibular peptide of 39 residues work?

Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation. Induces protein kinase C beta activation, recruitment of beta-arrestin and PTH2R internalization. May inhibit cell proliferation via its action on PTH2R activation. Neuropeptide which may also have a role in spermatogenesis. May activate nociceptors and nocicep

What is the research status of Tuberoinfundibular peptide of 39 residues?

Tuberoinfundibular peptide of 39 residues is currently classified as experimental, with 3 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Tuberoinfundibular peptide of 39 residues?

Tuberoinfundibular peptide of 39 residues has a molecular weight of approximately 11202 g/mol.

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