Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV5C5VT)

• DOT Name: Tuberoinfundibular peptide of 39 residues (PTH2)
• Synonyms: TIP39; Parathyroid hormone 2
• Gene Name: PTH2
• Related Disease:
  Small-cell lung cancer
  Darier disease
• UniProt ID: TIP39_HUMAN
• PDB ID: 7F16
• Pfam ID: PF14980
• Sequence:
  METRQVSRSPRVRLLLLLLLLLVVPWGVRTASGVALPPVGVLSLRPPGRAWADPATPRPR
  RSLALADDAAFRERARLLAALERRHWLNSYMHKLLVLDAP
• Function: 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.
• Tissue Specificity: Highly expressed in fetal and adult brain, cerebellum and trachea. Weakly expressed in spinal cord, fetal liver, kidney and heart.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Class B/2 (Secretin family receptors) (R-HSA-373080)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small-cell lung cancer	DISK3LZD	Strong	Altered Expression	[1]
Darier disease	DIS4WI7S	Limited	Biomarker	[2]

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tuberoinfundibular peptide of 39 residues (PTH2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tuberoinfundibular peptide of 39 residues (PTH2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tuberoinfundibular peptide of 39 residues (PTH2).	[5]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tuberoinfundibular peptide of 39 residues (PTH2).	[6]

References

• [1] Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines.Oncogene. 1998 Jan 8;16(1):89-93. doi: 10.1038/sj.onc.1201512.
• [2] The parathyroid hormone family member TIP39 interacts with sarco/endoplasmic reticulum Ca(2+) - ATPase activity by influencing calcium homoeostasis.Exp Dermatol. 2017 Sep;26(9):792-797. doi: 10.1111/exd.13294. Epub 2017 Apr 21.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.