Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAP7L6G)

• DOT Name: PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1)
• Synonyms: Liver-related putative tumor suppressor; Pin2-interacting protein X1; Protein 67-11-3; TRF1-interacting protein 1
• Gene Name: PINX1
• UniProt ID: PINX1_HUMAN
• Pfam ID: PF01585
• Sequence:
  MSMLAERRRKQKWAVDPQNTAWSNDDSKFGQRMLEKMGWSKGKGLGAQEQGATDHIKVQV
  KNNHLGLGATINNEDNWIAHQDDFNQLLAELNTCHGQETTDSSDKKEKKSFSLEEKSKIS
  KNRVHYMKFTKGKDLSSRSKTDLDCIFGKRQSKKTPEGDASPSTPEENETTTTSAFTIQE
  YFAKRMAALKNKPQVPVPGSDISETQVERKRGKKRNKEATGKDVESYLQPKAKRHTEGKP
  ERAEAQERVAKKKSAPAEEQLRGPCWDQSSKASAQDAGDHVQPPEGRDFTLKPKKRRGKK
  KLQKPVEIAEDATLEETLVKKKKKKDSK
• Function: Microtubule-binding protein essential for faithful chromosome segregation. Mediates TRF1 and TERT accumulation in nucleolus and enhances TRF1 binding to telomeres. Inhibits telomerase activity. May inhibit cell proliferation and act as tumor suppressor.
• Tissue Specificity: Ubiquitous; expressed at low levels. Not detectable in a number of hepatocarcinoma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of PIN2/TERF1-interacting telomerase inhibitor 1 (PINX1).	[4]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [3] Cytotoxic effect of arsenic trioxide on acute promyelocytic leukemia cells through suppression of NFk-dependent induction of hTERT due to down-regulation of Pin1 transcription. Hematology. 2012 Jul;17(4):198-206. doi: 10.1179/1607845412Y.0000000008.
• [4] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [6] 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.