Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NVSWU)

• DOT Name: Tuftelin-interacting protein 11 (TFIP11)
• Synonyms: Septin and tuftelin-interacting protein 1; STIP-1
• Gene Name: TFIP11
• Related Disease:
  Allergic asthma
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Colitis
  Inflammatory bowel disease
  Non-small-cell lung cancer
  Pachyonychia congenita 3
  Pancreatic ductal carcinoma
  Pancreatic tumour
  Pancreatitis
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Gastric cancer
  Stomach cancer
  Acute lymphocytic leukaemia
  Atopic dermatitis
  Carcinoma
  Chronic urticaria
  Colorectal carcinoma
  Dental caries
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lymphoid leukemia
  Metastatic malignant neoplasm
  Pancreatic cancer
• UniProt ID: TFP11_HUMAN
• Pfam ID: PF01585 ; PF07842 ; PF12457
• Sequence:
  MSLSHLYRDGEGRIDDDDDERENFEITDWDLQNEFNPNRQRHWQTKEEATYGVWAERDSD
  DERPSFGGKRARDYSAPVNFISAGLKKGAAEEAELEDSDDEEKPVKQDDFPKDFGPRKLK
  TGGNFKPSQKGFAGGTKSFMDFGSWERHTKGIGQKLLQKMGYVPGRGLGKNAQGIINPIE
  AKQRKGKGAVGAYGSERTTQSMQDFPVVDSEEEAEEEFQKELSQWRKDPSGSKKKPKYSY
  KTVEELKAKGRISKKLTAPQKELSQVKVIDMTGREQKVYYSYSQISHKHNVPDDGLPLQS
  QQLPQSGKEAKAPGFALPELEHNLQLLIDLTEQEIIQNDRQLQYERDMVVNLFHELEKMT
  EVLDHEERVISNLSKVLEMVEECERRMQPDCSNPLTLDECARIFETLQDKYYEEYRMSDR
  VDLAVAIVYPLMKEYFKEWDPLKDCTYGTEIISKWKSLLENDQLLSHGGQDLSADAFHRL
  IWEVWMPFVRNIVTQWQPRNCDPMVDFLDSWVHIIPVWILDNILDQLIFPKLQKEVENWN
  PLTDTVPIHSWIHPWLPLMQARLEPLYSPIRSKLSSALQKWHPSDSSAKLILQPWKDVFT
  PGSWEAFMVKNIVPKLGMCLGELVINPHQQHMDAFYWVIDWEGMISVSSLVGLLEKHFFP
  KWLQVLCSWLSNSPNYEEITKWYLGWKSMFSDQVLAHPSVKDKFNEALDIMNRAVSSNVG
  AYMQPGARENIAYLTHTERRKDFQYEAMQERREAENMAQRGIGVAASSVPMNFKDLIETK
  AEEHNIVFMPVIGKRHEGKQLYTFGRIVIYIDRGVVFVQGEKTWVPTSLQSLIDMAK
• Function: Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events. Intron turnover seems to proceed through reactions in two lariat-intron associated complexes termed Intron Large (IL) and Intron Small (IS). In cooperation with DHX15 seems to mediate the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns. May play a role in the differentiation of ameloblasts and odontoblasts or in the forming of the enamel extracellular matrix.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic asthma	DISHF0H3	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[3]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Pachyonychia congenita 3	DISZLC6C	Strong	Biomarker	[7]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[8]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[9]
Pancreatitis	DIS0IJEF	Strong	Altered Expression	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Psoriasis	DIS59VMN	Strong	Biomarker	[10]
Gastric cancer	DISXGOUK	moderate	Biomarker	[11]
Stomach cancer	DISKIJSX	moderate	Biomarker	[11]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[12]
Atopic dermatitis	DISTCP41	Limited	Biomarker	[13]
Carcinoma	DISH9F1N	Limited	Biomarker	[14]
Chronic urticaria	DISMBYB0	Limited	Altered Expression	[13]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[15]
Dental caries	DISRBCMD	Limited	Genetic Variation	[16]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[17]
leukaemia	DISS7D1V	Limited	Biomarker	[12]
Leukemia	DISNAKFL	Limited	Biomarker	[12]
Lymphoid leukemia	DIS65TYQ	Limited	Altered Expression	[12]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[17]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Tuftelin-interacting protein 11 (TFIP11).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tuftelin-interacting protein 11 (TFIP11).	[19]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Tuftelin-interacting protein 11 (TFIP11).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Tuftelin-interacting protein 11 (TFIP11).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tuftelin-interacting protein 11 (TFIP11).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Tuftelin-interacting protein 11 (TFIP11).	[23]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Tuftelin-interacting protein 11 (TFIP11).	[22]

References

• [1] Beneficial Effects of Neurotensin in Murine Model of Hapten-Induced Asthma.Int J Mol Sci. 2019 Oct 11;20(20):5025. doi: 10.3390/ijms20205025.
• [2] Protective Effect of Notoginsenoside R1 on an APP/PS1 Mouse Model of Alzheimer's Disease by Up-Regulating Insulin Degrading Enzyme and Inhibiting A Accumulation.CNS Neurol Disord Drug Targets. 2015;14(3):360-9. doi: 10.2174/1871527314666150225141521.
• [3] De novo single-nucleotide and copy number variation in discordant monozygotic twins reveals disease-related genes. Eur J Hum Genet. 2019 Jul;27(7):1121-1133. doi: 10.1038/s41431-019-0376-7. Epub 2019 Mar 18.
• [4] Neurotensin Promotes the Development of Colitis and Intestinal Angiogenesis via Hif-1-miR-210 Signaling.J Immunol. 2016 May 15;196(10):4311-21. doi: 10.4049/jimmunol.1501443. Epub 2016 Apr 13.
• [5] Insulin-like growth factor-1 receptor transactivation modulates the inflammatory and proliferative responses of neurotensin in human colonic epithelial cells.J Biol Chem. 2011 Feb 25;286(8):6092-9. doi: 10.1074/jbc.M110.192534. Epub 2011 Jan 6.
• [6] STIP overexpression confers oncogenic potential to human non-small cell lung cancer cells by regulating cell cycle and apoptosis.J Cell Mol Med. 2015 Dec;19(12):2806-17. doi: 10.1111/jcmm.12670. Epub 2015 Sep 10.
• [7] Development of Bispecific NT-PSMA Heterodimer for Prostate Cancer Imaging: A Potential Approach to Address Tumor Heterogeneity.Bioconjug Chem. 2019 May 15;30(5):1314-1322. doi: 10.1021/acs.bioconjchem.9b00252. Epub 2019 May 7.
• [8] Evaluation of neurotensin receptor 1 as a potential imaging target in pancreatic ductal adenocarcinoma.Amino Acids. 2017 Aug;49(8):1325-1335. doi: 10.1007/s00726-017-2430-5. Epub 2017 May 23.
• [9] Development of [(18)F]AlF-NOTA-NT as PET Agents of Neurotensin Receptor-1 Positive Pancreatic Cancer.Mol Pharm. 2018 Aug 6;15(8):3093-3100. doi: 10.1021/acs.molpharmaceut.8b00192. Epub 2018 Jun 26.
• [10] Serum neurotensin (NT) is increased in psoriasis and NT induces vascular endothelial growth factor release from human mast cells.Br J Dermatol. 2012 Jun;166(6):1349-52. doi: 10.1111/j.1365-2133.2012.10843.x. Epub 2012 May 14.
• [11] Validation of Neurotensin Receptor 1 as a Therapeutic Target for Gastric Cancer.Mol Cells. 2018 Jun;41(6):591-602. doi: 10.14348/molcells.2018.0025. Epub 2018 May 24.
• [12] STIP Regulates ERK1/2 Signaling Pathway Involved in Interaction with PP1 in Lymphoblastic Leukemia.Curr Mol Med. 2016;16(8):767-775. doi: 10.2174/1566524016666161018154401.
• [13] Neurotensin serum levels and skin gene expression are increased in atopic dermatitis.Br J Dermatol. 2013 Sep;169(3):695-9. doi: 10.1111/bjd.12413.
• [14] Neurotensin receptor-1 mRNA analysis in normal pancreas and pancreatic disease.Clin Cancer Res. 2000 Feb;6(2):566-71.
• [15] Suppression of neurotensin receptor type 1 expression and function by histone deacetylase inhibitors in human colorectal cancers.Mol Cancer Ther. 2010 Aug;9(8):2389-98. doi: 10.1158/1535-7163.MCT-09-1080. Epub 2010 Jul 27.
• [16] Effects of enamel matrix genes on dental caries are moderated by fluoride exposures.Hum Genet. 2015 Feb;134(2):159-67. doi: 10.1007/s00439-014-1504-7. Epub 2014 Nov 6.
• [17] Neurotensin/IL-8 pathway orchestrates local inflammatory response and tumor invasion by inducing M2 polarization of Tumor-Associated macrophages and epithelial-mesenchymal transition of hepatocellular carcinoma cells.Oncoimmunology. 2018 Mar 13;7(7):e1440166. doi: 10.1080/2162402X.2018.1440166. eCollection 2018.
• [18] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood. 2005 Feb 1;105(3):1214-21. doi: 10.1182/blood-2004-03-1182. Epub 2004 Sep 28.
• [21] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [22] 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.
• [23] 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.