Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR3K733)

• DOT Name: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2)
• Synonyms: EC 3.1.3.67; Lipid phosphatase TPIP; TPTE and PTEN homologous inositol lipid phosphatase
• Gene Name: TPTE2
• Related Disease:
  Parkinson disease
  Coronary heart disease
  Gallbladder cancer
  Gallbladder carcinoma
• UniProt ID: TPTE2_HUMAN
• EC Number: 3.1.3.67
• Pfam ID: PF00520 ; PF10409 ; PF00102
• Sequence:
  MNESPQTNEFKGTTEEAPAKESPHTSEFKGAALVSPISKSMLERLSKFEVEDAENVASYD
  SKIKKIVHSIVSSFAFGIFGVFLVLLDVTLLLADLIFTDSKLYIPLEYRSISLAIGLFFL
  MDVLLRVFVEGRQQYFSDLFNILDTAIIVIPLLVDVIYIFFDIKLLRNIPRWTHLVRLLR
  LIILIRIFHLLHQKRQLEKLMRRLVSENKRRYTRDGFDLDLTYVTERIIAMSFPSSGRQS
  FYRNPIEEVVRFLDKKHRNHYRVYNLCSERAYDPKHFHNRVSRIMIDDHNVPTLHEMVVF
  TKEVNEWMAQDLENIVAIHCKGGKGRTGTMVCALLIASEIFLTAEESLYYFGERRTNKTH
  SNKFQGVETPSQNRYVGYFAQVKHLYNWNLPPRRILFIKRFIIYSIRGDVCDLKVQVVME
  KKVVFSSTSLGNCSILHDIETDKILINVYDGPPLYDDVKVQFFSSNLPKYYDNCPFFFWF
  NTSFIQNNRLCLPRNELDNPHKQKAWKIYPPEFAVEILFGEK
• Function: Acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate; [Isoform 4]: Shows no phosphoinositide phosphatase activity.
• Tissue Specificity: Isoform 3 is expressed in testis, brain and stomach while isoform 4 seems to be testis-specific.
• Reactome Pathway: Synthesis of PIPs at the Golgi membrane (R-HSA-1660514)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[2]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[3]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2).	[4]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2).	[5]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2).	[6]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase TPTE2 (TPTE2).	[8]

References

• [1] Genome-wide association study identifies candidate genes for Parkinson's disease in an Ashkenazi Jewish population.BMC Med Genet. 2011 Aug 3;12:104. doi: 10.1186/1471-2350-12-104.
• [2] Genomewide association analysis of coronary artery disease.N Engl J Med. 2007 Aug 2;357(5):443-53. doi: 10.1056/NEJMoa072366. Epub 2007 Jul 18.
• [3] Downregulation of TPTE2P1 Inhibits Migration and Invasion of Gallbladder Cancer Cells.Chem Biol Drug Des. 2015 Oct;86(4):656-62. doi: 10.1111/cbdd.12533. Epub 2015 May 11.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [7] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.