TIP39 explained

Tuberoinfundibular peptide of 39 residues is a protein that in humans is encoded by the PTH2 gene.^{[1] [2]}

TIP39 is related to parathyroid hormone (PTH; MIM 168450) and PTH-related protein (PTHRP; MIM 168470) and is a ligand for PTH receptor-2 (PTHR2; MIM 601469) (John et al., 2002).[supplied by OMIM]^[3]

The molecular interaction of TIP39 with the PTH2 receptor 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 ^[4]

Expression of TIP39 has been linked to social interaction in both zebrafish ^[5] and rats.^[6] In these species, mutations of TIP39 or its receptor lead to abnormal social behavior.^{[7] [8]}

Further reading

• Usdin TB, Hoare SR, Wang T, etal . TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. . Nat. Neurosci. . 2 . 11 . 941–3 . 1999 . 10526330 . 10.1038/14724 . 22744817 .
• 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.
• Dobolyi A, Ueda H, Uchida H, etal . Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 3 . 1651–6 . 2002 . 11818570 . 10.1073/pnas.042416199 . 122245 . 2002PNAS...99.1651D . free .
• Hansen IA, Jakob O, Wortmann S, etal . Characterization of the human and mouse genes encoding the tuberoinfundibular peptide of 39 residues, a ligand of the parathyroid hormone receptor family. . J. Endocrinol. . 174 . 1 . 95–102 . 2002 . 12098667 . 10.1677/joe.0.1740095 . 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 .
• Della Penna K, Kinose F, Sun H, etal . Tuberoinfundibular peptide of 39 residues (TIP39): molecular structure and activity for parathyroid hormone 2 receptor. . Neuropharmacology . 44 . 1 . 141–53 . 2003 . 12559132 . 10.1016/S0028-3908(02)00335-0 . 9974844 .
• Misiano P, Scott BB, Scheideler MA, Garnier M . PTH2 receptor-mediated inhibitory effect of parathyroid hormone and TIP39 on cell proliferation. . Eur. J. Pharmacol. . 468 . 3 . 159–66 . 2004 . 12754053 . 10.1016/S0014-2999(03)01673-X .
• 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 .

Notes and References

1. John MR, Arai M, Rubin DA, Jonsson KB, Juppner H . Identification and characterization of the murine and human gene encoding the tuberoinfundibular peptide of 39 residues . Endocrinology . 143 . 3 . 1047–57 . Feb 2002 . 11861531 . 10.1210/endo.143.3.8698 . free .
2. Web site: Entrez Gene: TIP39 tuberoinfundibular 39 residue protein precursor.
3. Web site: Entrez Gene: TIP39 tuberoinfundibular 39 residue protein precursor.
4. 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 .
5. Anneser L, Alcantara I, Gemmer A, Mirkes K, Ryu S, Schuman EM . The neuropeptide Pth2 dynamically senses others via mechanosensation. . Nature . 588 . 653–657. 2020. 7839 . 33268890. 10.1038/s41586-020-2988-z. 10871/123941. free.
6. Keller D, Láng T, Cservenák M, Puska G, Barna J, Csillag V, Farkas I, Zelena D, Dóra F, Küppers S, Barteczko L, Usdin TB, Palkovits M, Hasan MT, Grinevich V, Dobolyi A. A thalamo-preoptic pathway promotes social grooming in rodents. Current Biology. 32. 4593–4606. 2022. 21 . 36113471. 10.1016/j.cub.2022.08.062. free.
7. Anneser L, Gemmer A, Eilers T, Alcantara I, Loos AY, Ryu S, Schuman EM. The neuropeptide Pth2 modulates social behavior and anxiety in zebrafish.. iScience . 25. 2022. 3 . 103868. 35243231. 10.1016/j.isci.2022.103868. 8861652.
8. Gellén B, Zelena D, Usdin TB, Dobolyi A. The parathyroid hormone 2 receptor participates in physiological and behavioral alterations of mother mice.. Physiology and Behavior. 2017. 181. 51–58. 28890271. 10.1016/j.physbeh.2017.09.005. 40314841 .