Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX21QTE)

• DOT Name: Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1IP)
• Synonyms: Pituitary tumor-transforming gene protein-binding factor; PBF; PTTG-binding factor
• Gene Name: PTTG1IP
• Related Disease:
  Bone osteosarcoma
  Breast cancer
  Carcinoma of esophagus
  Estrogen-receptor positive breast cancer
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Human papillomavirus infection
  Malignant soft tissue neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Pituitary tumor
  Sarcoma
  Thyroid cancer
  Thyroid gland carcinoma
  Type-1/2 diabetes
  Advanced cancer
  Asthma
  Breast carcinoma
  Chromosomal disorder
  Differentiated thyroid carcinoma
  Thyroid tumor
• UniProt ID: PTTG_HUMAN
• Sequence:
  MAPGVARGPTPYWRLRLGGAALLLLLIPVAAAQEPPGAACSQNTNKTCEECLKNVSCLWC
  NTNKACLDYPVTSVLPPASLCKLSSARWGVCWVNFEALIITMSVVGGTLLLGIAICCCCC
  CRRKRSRKPDRSEEKAMREREERRIRQEERRAEMKTRHDEIRKKYGLFKEENPYARFENN
• Function: May facilitate PTTG1 nuclear translocation.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[2]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Genetic Variation	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[6]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[6]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[6]
Human papillomavirus infection	DISX61LX	Strong	Altered Expression	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[8]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[1]
Pituitary tumor	DISN67JD	Strong	Genetic Variation	[9]
Sarcoma	DISZDG3U	Strong	Altered Expression	[7]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[10]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[10]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[11]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[9]
Asthma	DISW9QNS	Limited	Biomarker	[12]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[2]
Chromosomal disorder	DISM5BB5	Limited	Altered Expression	[10]
Differentiated thyroid carcinoma	DIS1V20Y	Limited	Genetic Variation	[13]
Thyroid tumor	DISLVKMD	Limited	Biomarker	[10]

2 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 affects the methylation of Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1IP).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1IP).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1IP).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Pituitary tumor-transforming gene 1 protein-interacting protein (PTTG1IP).	[17]

References

• [1] Development of a T-cell receptor multimer with high avidity for detecting a naturally presented tumor-associated antigen on osteosarcoma cells.Cancer Sci. 2019 Jan;110(1):40-51. doi: 10.1111/cas.13854. Epub 2018 Dec 1.
• [2] PTTG1-interacting protein (PTTG1IP/PBF) predicts breast cancer survival.BMC Cancer. 2017 Oct 27;17(1):705. doi: 10.1186/s12885-017-3694-6.
• [3] PBF, a Proto-oncogene in Esophageal Carcinoma.Open Med (Wars). 2019 Oct 13;14:748-756. doi: 10.1515/med-2019-0086. eCollection 2019.
• [4] Functional variable number of tandem repeats variation in the promoter of proto-oncogene PTTG1IP is associated with risk of estrogen receptor-positive breast cancer.Cancer Sci. 2012 Jun;103(6):1121-8. doi: 10.1111/j.1349-7006.2012.02266.x. Epub 2012 Apr 12.
• [5] MicroRNA-584 functions as a tumor suppressor and targets PTTG1IP in glioma.Int J Clin Exp Pathol. 2014 Dec 1;7(12):8573-82. eCollection 2014.
• [6] PTTG and PBF Functionally Interact with p53 and Predict Overall Survival in Head and Neck Cancer.Cancer Res. 2018 Oct 15;78(20):5863-5876. doi: 10.1158/0008-5472.CAN-18-0855. Epub 2018 Aug 28.
• [7] Specific targeting of a naturally presented osteosarcoma antigen, papillomavirus binding factor peptide, using an artificial monoclonal antibody.J Biol Chem. 2014 Aug 8;289(32):22035-47. doi: 10.1074/jbc.M114.568725. Epub 2014 Jun 24.
• [8] A Novel Antagonist of the Immune Checkpoint Protein Adenosine A2a Receptor Restores Tumor-Infiltrating Lymphocyte Activity in the Context of the Tumor Microenvironment.Neoplasia. 2017 Jul;19(7):530-536. doi: 10.1016/j.neo.2017.02.004. Epub 2017 Jun 3.
• [9] Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF.Endocr Relat Cancer. 2017 Sep;24(9):459-474. doi: 10.1530/ERC-16-0340. Epub 2017 Jul 4.
• [10] Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer.Oncogene. 2017 Sep 14;36(37):5296-5308. doi: 10.1038/onc.2017.154. Epub 2017 May 15.
• [11] Effects of Excessive Body Fat Accumulation on Long-Term Outcomes During Peritoneal Dialysis.Perit Dial Int. 2019 May-Jun;39(3):268-275. doi: 10.3747/pdi.2018.00164. Epub 2019 Mar 6.
• [12] PTTG1IP and MAML3, novel genomewide association study genes for severity of hyperresponsiveness in adult asthma.Allergy. 2017 May;72(5):792-801. doi: 10.1111/all.13062. Epub 2016 Nov 21.
• [13] The PTTG1-binding factor (PBF/PTTG1IP) regulates p53 activity in thyroid cells.Endocrinology. 2014 Apr;155(4):1222-34. doi: 10.1210/en.2013-1646. Epub 2014 Feb 7.
• [14] 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.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.