Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0GTBXO)

• DOT Name: Tumor protein p53-inducible nuclear protein 2 (TP53INP2)
• Synonyms: Diabetes and obesity-regulated gene; p53-inducible protein U; PIG-U
• Gene Name: TP53INP2
• Related Disease:
  Adenoma
  Adult lymphoma
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cerebellar ataxia
  Constipation
  Fibromyalgia
  Head-neck squamous cell carcinoma
  Lymphoma
  Nephropathy
  Pediatric lymphoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Colorectal carcinoma
  Liposarcoma
  Melanoma
• UniProt ID: T53I2_HUMAN
• PDB ID: 7YO9
• Pfam ID: PF14839
• Sequence:
  MFQRLSSLFFSTPSPPEDPDCPRAFVSEEDEVDGWLIIDLPDSYAAPPSPGAAPAPAGRP
  PPAPSLMDESWFVTPPACFTAEGPGLGPARLQSSPLEDLLIEHPSMSVYVTGSTIVLEPG
  SPSPLPDAALPDGDLSEGELTPARREPRAARHAAPLPARAALLEKAGQVRRLQRARQRAE
  RHALSAKAVQRQNRARESRPRRSKNQSSFIYQPCQRQFNY
• Function: Dual regulator of transcription and autophagy. Positively regulates autophagy and is required for autophagosome formation and processing. May act as a scaffold protein that recruits MAP1LC3A, GABARAP and GABARAPL2 and brings them to the autophagosome membrane by interacting with VMP1 where, in cooperation with the BECN1-PI3-kinase class III complex, they trigger autophagosome development. Acts as a transcriptional activator of THRA.
• KEGG Pathway: Autophagy - animal (hsa04140)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenoma	DIS78ZEV	Strong	Biomarker	[1]
Adult lymphoma	DISK8IZR	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[5]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[6]
Constipation	DISRQXWI	Strong	Biomarker	[7]
Fibromyalgia	DISZJDS2	Strong	Altered Expression	[8]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[9]
Lymphoma	DISN6V4S	Strong	Altered Expression	[2]
Nephropathy	DISXWP4P	Strong	Altered Expression	[10]
Pediatric lymphoma	DIS51BK2	Strong	Altered Expression	[2]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[11]
Liposarcoma	DIS8IZVM	moderate	Altered Expression	[12]
Melanoma	DIS1RRCY	Limited	Altered Expression	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[16]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[15]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[18]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[19]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[19]
Marinol	DM70IK5	Approved	Marinol increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[20]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[21]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[22]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[26]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[28]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[29]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[30]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tumor protein p53-inducible nuclear protein 2 (TP53INP2).	[25]

References

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• [5] CDC91L1 (PIG-U) mRNA expression in urothelial cell carcinomas.Int J Cancer. 2005 Aug 20;116(2):282-4. doi: 10.1002/ijc.21040.
• [6] The coding region of TP53INP2, a gene expressed in the developing nervous system, is not altered in a family with autosomal recessive non-progressive infantile ataxia on chromosome 20q11-q13.Dev Dyn. 2007 Mar;236(3):843-52. doi: 10.1002/dvdy.21064.
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• [8] Skin cytokine expression in patients with fibromyalgia syndrome is not different from controls.BMC Neurol. 2014 Sep 22;14:185. doi: 10.1186/s12883-014-0185-0.
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• [12] TP53INP2-related basal autophagy is involved in the growth and malignant progression in human liposarcoma cells.Biomed Pharmacother. 2017 Apr;88:562-568. doi: 10.1016/j.biopha.2017.01.110. Epub 2017 Feb 24.
• [13] miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy.Oncotarget. 2015 Feb 20;6(5):2966-80. doi: 10.18632/oncotarget.3070.
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• [17] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [20] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [21] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [22] Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem. 2004 Mar;88(5):1211-9. doi: 10.1046/j.1471-4159.2003.02247.x.
• [23] Capsaicin inhibits the migration, invasion and EMT of renal cancer cells by inducing AMPK/mTOR-mediated autophagy. Chem Biol Interact. 2022 Oct 1;366:110043. doi: 10.1016/j.cbi.2022.110043. Epub 2022 Aug 28.
• [24] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
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• [27] 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.
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• [29] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [30] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
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