Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX0PCR3)

• DOT Name: T-cell immunomodulatory protein (ITFG1)
• Synonyms: Protein TIP; Integrin-alpha FG-GAP repeat-containing protein 1; Linkin
• Gene Name: ITFG1
• Related Disease:
  Acute graft versus host disease
  Acute otitis media
  Adult teratoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cystic fibrosis
  Invasive breast carcinoma
  Joubert syndrome
  Neoplasm
  Otitis media
  Teratoma
  Graft-versus-host disease
• UniProt ID: TIP_HUMAN
• Pfam ID: PF13517
• Sequence:
  MAAAGRLPSSWALFSPLLAGLALLGVGPVPARALHNVTAELFGAEAWGTLAAFGDLNSDK
  QTDLFVLRERNDLIVFLADQNAPYFKPKVKVSFKNHSALITSVVPGDYDGDSQMDVLLTY
  LPKNYAKSELGAVIFWGQNQTLDPNNMTILNRTFQDEPLIMDFNGDLIPDIFGITNESNQ
  PQILLGGNLSWHPALTTTSKMRIPHSHAFIDLTEDFTADLFLTTLNATTSTFQFEIWENL
  DGNFSVSTILEKPQNMMVVGQSAFADFDGDGHMDHLLPGCEDKNCQKSTIYLVRSGMKQW
  VPVLQDFSNKGTLWGFVPFVDEQQPTEIPIPITLHIGDYNMDGYPDALVILKNTSGSNQQ
  AFLLENVPCNNASCEEARRMFKVYWELTDLNQIKDAMVATFFDIYEDGILDIVVLSKGYT
  KNDFAIHTLKNNFEADAYFVKVIVLSGLCSNDCPRKITPFGVNQPGPYIMYTTVDANGYL
  KNGSAGQLSQSAHLALQLPYNVLGLGRSANFLDHLYVGIPRPSGEKSIRKQEWTAIIPNS
  QLIVIPYPHNVPRSWSAKLYLTPSNIVLLTAIALIGVCVFILAIIGILHWQEKKADDREK
  RQEAHRFHFDAM
• Function: Modulator of T-cell function. Has a protective effect in graft versus host disease model.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute graft versus host disease	DIS8KLVM	Strong	Biomarker	[1]
Acute otitis media	DISL8D8G	Strong	Biomarker	[2]
Adult teratoma	DISBY81U	Strong	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[6]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[7]
Invasive breast carcinoma	DISANYTW	Strong	Biomarker	[5]
Joubert syndrome	DIS7P5CO	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Otitis media	DISGZDUO	Strong	Biomarker	[2]
Teratoma	DIS6ICY4	Strong	Genetic Variation	[3]
Graft-versus-host disease	DIS0QADF	Limited	Biomarker	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of T-cell immunomodulatory protein (ITFG1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of T-cell immunomodulatory protein (ITFG1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of T-cell immunomodulatory protein (ITFG1).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of T-cell immunomodulatory protein (ITFG1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of T-cell immunomodulatory protein (ITFG1).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of T-cell immunomodulatory protein (ITFG1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of T-cell immunomodulatory protein (ITFG1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of T-cell immunomodulatory protein (ITFG1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of T-cell immunomodulatory protein (ITFG1).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of T-cell immunomodulatory protein (ITFG1).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of T-cell immunomodulatory protein (ITFG1).	[17]

References

• [1] Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria.Korean J Parasitol. 2019 Apr;57(2):101-115. doi: 10.3347/kjp.2019.57.2.101. Epub 2019 Apr 30.
• [2] The "TIP algorithm" for the accurate diagnosis of pediatric otitis media.Int J Pediatr Otorhinolaryngol. 2019 Sep;124:185-189. doi: 10.1016/j.ijporl.2019.05.028. Epub 2019 May 27.
• [3] Surgical Management of Patients with Advanced Germ Cell Tumors Following Salvage Chemotherapy: Memorial Sloan Kettering Cancer Center (MSKCC) Experience.Urology. 2019 Feb;124:174-178. doi: 10.1016/j.urology.2018.09.024. Epub 2018 Oct 6.
• [4] TIP: A Web Server for Resolving Tumor Immunophenotype Profiling.Cancer Res. 2018 Dec 1;78(23):6575-6580. doi: 10.1158/0008-5472.CAN-18-0689. Epub 2018 Aug 28.
• [5] RUVBL1-ITFG1 interaction is required for collective invasion in breast cancer.Biochim Biophys Acta Gen Subj. 2017 Jul;1861(7):1788-1800. doi: 10.1016/j.bbagen.2017.03.016. Epub 2017 Mar 21.
• [6] #NAME?
• [7] Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.Clin Drug Investig. 2017 Aug;37(8):795-805. doi: 10.1007/s40261-017-0537-9.
• [8] A CEP104-CSPP1 Complex Is Required for Formation of Primary Cilia Competent in Hedgehog Signaling.Cell Rep. 2019 Aug 13;28(7):1907-1922.e6. doi: 10.1016/j.celrep.2019.07.025.
• [9] TIP, a T-cell factor identified using high-throughput screening increases survival in a graft-versus-host disease model.Nat Biotechnol. 2003 Mar;21(3):302-7. doi: 10.1038/nbt797. Epub 2003 Feb 24.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [12] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [16] 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.
• [17] 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.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [19] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.