Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO3JDX5)

• DOT Name: Protein ITPRID2 (ITPRID2)
• Synonyms: Cleavage signal-1 protein; CS-1; ITPR-interacting domain-containing protein 2; Ki-ras-induced actin-interacting protein; Sperm-specific antigen 2
• Gene Name: ITPRID2
• Related Disease:
  Neoplasm
  Adult germ cell tumor
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Germ cell tumor
  Germ cell tumour
  Glioblastoma multiforme
  Glioma
  Non-small-cell lung cancer
  Nongerminomatous germ cell tumor
  Obesity
  Plasma cell myeloma
  Testicular germ cell tumor
  Type-1/2 diabetes
• UniProt ID: ITPI2_HUMAN
• Pfam ID: PF14722 ; PF14723
• Sequence:
  MDRPLSSSAEAEEELEWQVASRRRKAWAKCRSSWQASETEDLSTEATTQDEEEDEEEDLP
  GAQLPAAGGRGNVPNEKIAIWLKDCRTPLGASLDEQSSSTLKGVLVRNGGSFEDDLSLGA
  EANHLHESDAQIENCNNILAKERRLQFHQKGRSMNSTGSGKSSGTVSSVSELLELYEEDP
  EEILYNLGFGRDEPDIASKIPSRFFNSSSFAKGIDIKVFLSAQMQRMEVENPNYALTSRF
  RQIEVLTTVANAFSSLYSQVSGTPLQRIGSMSSVTSNKETDPPPPLTRSNTANRLMKTLS
  KLNLCVDKTEKGESSSPSPSAEKGKILNVSVIEESGNKNDQKSQKIMKKKESSSMLATVK
  EEVSGSSAAVTENADSDRISDEANSNFNQGTENEQSKETQSHESKLGEESGIVESKLDSD
  FNISSHSELENSSELKSVHISTPEKEPCAPLTIPSIRNIMTQQKDSFEMEEVQSTEGEAP
  HVPATYQLGLTKSKRDHLLRTASQHSDSSGFAEDSTDCLSLNHLQVQESLQAMGSSADSC
  DSETTVTSLGEDLATPTAQDQPYFNESEEESLVPLQKGLEKAAAVADKRKSGSQDFPQCN
  TIENTGTKQSTCSPGDHIIEITEVEEDLFPAETVELLREASAESDVGKSSESEFTQYTTH
  HILKSLASIEAKCSDMSSENTTGPPSSMDRVNTALQRAQMKVCSLSNQRMGRSLLKSKDL
  LKQRYLFAKAGYPLRRSQSLPTTLLSPVRVVSSVNVRLSPGKETRCSPPSFTYKYTPEEE
  QELEKRVMEHDGQSLVKSTIFISPSSVKKEEAPQSEAPRVEECHHGRTPTCSRLAPPPMS
  QSTCSLHSIHSEWQERPLCEHTRTLSTHSVPNISGATCSAFASPFGCPYSHRHATYPYRV
  CSVNPPSAIEMQLRRVLHDIRNSLQNLSQYPMMRGPDPAAAPYSTQKSSVLPLYENTFQE
  LQVMRRSLNLFRTQMMDLELAMLRQQTMVYHHMTEEERFEVDQLQGLRNSVRMELQDLEL
  QLEERLLGLEEQLRAVRMPSPFRSSALMGMCGSRSADNLSCPSPLNVMEPVTELMQEQSY
  LKSELGLGLGEMGFEIPPGESSESVFSQATSESSSVCSGPSHANRRTGVPSTASVGKSKT
  PLVARKKVFRASVALTPTAPSRTGSVQTPPDLESSEEVDAAEGAPEVVGPKSEVEEGHGK
  LPSMPAAEEMHKNVEQDELQQVIREIKESIVGEIRREIVSGLLAAVSSSKASNSKQDYH
• Tissue Specificity: Strongly expressed in pancreas and testis. Present in colon cancer cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Adult germ cell tumor	DISJUCQ7	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Germ cell tumor	DIS62070	Strong	Biomarker	[2]
Germ cell tumour	DISOF3TK	Strong	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Nongerminomatous germ cell tumor	DISQOQJU	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[8]
Testicular germ cell tumor	DIS5RN24	Strong	Genetic Variation	[2]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[5]

5 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 Protein ITPRID2 (ITPRID2).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Protein ITPRID2 (ITPRID2).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein ITPRID2 (ITPRID2).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein ITPRID2 (ITPRID2).	[21]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Protein ITPRID2 (ITPRID2).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein ITPRID2 (ITPRID2).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein ITPRID2 (ITPRID2).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein ITPRID2 (ITPRID2).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein ITPRID2 (ITPRID2).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat affects the expression of Protein ITPRID2 (ITPRID2).	[14]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein ITPRID2 (ITPRID2).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Protein ITPRID2 (ITPRID2).	[13]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Protein ITPRID2 (ITPRID2).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein ITPRID2 (ITPRID2).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein ITPRID2 (ITPRID2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein ITPRID2 (ITPRID2).	[20]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Protein ITPRID2 (ITPRID2).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein ITPRID2 (ITPRID2).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein ITPRID2 (ITPRID2).	[24]

References

• [1] Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer.PLoS One. 2014 Oct 31;9(10):e110990. doi: 10.1371/journal.pone.0110990. eCollection 2014.
• [2] Economy of Standards: European Association of Urology Guideline Changes Influence Treatment Costs in Stage I Testicular Cancer Patients.Urol Int. 2018;100(3):279-287. doi: 10.1159/000486343. Epub 2018 Mar 7.
• [3] Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study.J Cell Biochem. 2018 Jul;119(7):5186-5221. doi: 10.1002/jcb.26554. Epub 2018 Mar 25.
• [4] Analysis of KRAP expression and localization, and genes regulated by KRAP in a human colon cancer cell line.J Hum Genet. 2007;52(12):978-984. doi: 10.1007/s10038-007-0204-8. Epub 2007 Oct 13.
• [5] KRAS-induced actin-interacting protein: a potent target for obesity, diabetes and cancer.Anticancer Res. 2011 Jul;31(7):2413-7.
• [6] Molecular mechanism of SSFA2 deletion inhibiting cell proliferation and promoting cell apoptosis in glioma.Pathol Res Pract. 2019 Mar;215(3):600-606. doi: 10.1016/j.prp.2018.12.035. Epub 2018 Dec 31.
• [7] Impact of Staging With Positron-emission Tomography (PET) and Comorbidities on Management and Survival of American Veterans With Stage I-III Non-Small Cell Lung Cancer.Am J Clin Oncol. 2018 May;41(5):513-518. doi: 10.1097/COC.0000000000000316.
• [8] Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma.Mol Cancer Ther. 2009 Sep;8(9):2616-24. doi: 10.1158/1535-7163.MCT-09-0483. Epub 2009 Sep 1.
• [9] 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.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] 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.
• [12] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [13] 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.
• [14] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [15] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [16] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [20] 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.
• [21] 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.
• [22] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [24] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [25] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.