Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZH80H)

DOT Name Tumor necrosis factor alpha-induced protein 2 (TNFAIP2)
Synonyms TNF alpha-induced protein 2; Primary response gene B94 protein
Gene Name TNFAIP2
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
Glioma ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
Nasopharyngeal carcinoma ( )
Neoplasm ( )
Promyelocytic leukaemia ( )
Stomach cancer ( )
Transitional cell carcinoma ( )
Urothelial carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Rheumatoid arthritis ( )
UniProt ID
TNAP2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF06046
Sequence
MSEASSEDLVPPLEAGAAPYREEEEAAKKKKEKKKKSKGLANVFCVFTKGKKKKGQPSSA
EPEDAAGSRQGLDGPPPTVEELKAALERGQLEAARPLLALERELAAAAAAGGVSEEELVR
RQSKVEALYELLRDQVLGVLRRPLEAPPERLRQALAVVAEQEREDRQAAAAGPGTSGLAA
TRPRRWLQLWRRGVAEAAEERMGQRPAAGAEVPESVFLHLGRTMKEDLEAVVERLKPLFP
AEFGVVAAYAESYHQHFAAHLAAVAQFELCERDTYMLLLWVQNLYPNDIINSPKLVGELQ
GMGLGSLLPPRQIRLLEATFLSSEAANVRELMDRALELEARRWAEDVPPQRLDGHCHSEL
AIDIIQITSQAQAKAESITLDLGSQIKRVLLVELPAFLRSYQRAFNEFLERGKQLTNYRA
NVIANINNCLSFRMSMEQNWQVPQDTLSLLLGPLGELKSHGFDTLLQNLHEDLKPLFKRF
THTRWAAPVETLENIIATVDTRLPEFSELQGCFREELMEALHLHLVKEYIIQLSKGRLVL
KTAEQQQQLAGYILANADTIQHFCTQHGSPATWLQPALPTLAEIIRLQDPSAIKIEVATY
ATCYPDFSKGHLSAILAIKGNLSNSEVKRIRSILDVSMGAQEPSRPLFSLIKVG
Function May play a role as a mediator of inflammation and angiogenesis.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [2]
Gastric cancer DISXGOUK Strong Genetic Variation [3]
Glioma DIS5RPEH Strong Biomarker [4]
Head and neck cancer DISBPSQZ Strong Genetic Variation [5]
Head and neck carcinoma DISOU1DS Strong Genetic Variation [5]
Head-neck squamous cell carcinoma DISF7P24 Strong Genetic Variation [6]
Nasopharyngeal carcinoma DISAOTQ0 Strong Altered Expression [7]
Neoplasm DISZKGEW Strong Altered Expression [8]
Promyelocytic leukaemia DISYGG13 Strong Biomarker [9]
Stomach cancer DISKIJSX Strong Genetic Variation [3]
Transitional cell carcinoma DISWVVDR Strong Altered Expression [8]
Urothelial carcinoma DISRTNTN Strong Altered Expression [8]
Cervical cancer DISFSHPF Limited Genetic Variation [10]
Cervical carcinoma DIST4S00 Limited Genetic Variation [10]
Rheumatoid arthritis DISTSB4J Limited Biomarker [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 17 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
28 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 necrosis factor alpha-induced protein 2 (TNFAIP2). [12]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [13]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [14]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [15]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [16]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [17]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [18]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [19]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [11]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [21]
Selenium DM25CGV Approved Selenium increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [22]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [23]
Hydroquinone DM6AVR4 Approved Hydroquinone increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [24]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [11]
Menthol DMG2KW7 Approved Menthol increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [25]
Prednisolone DMQ8FR2 Approved Prednisolone decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [11]
Methylprednisolone DM4BDON Approved Methylprednisolone decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [11]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [26]
Tamibarotene DM3G74J Phase 3 Tamibarotene increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [28]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [29]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [30]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [31]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [32]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [33]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [34]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [35]
N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE DM2D4KY Investigative N-(3-METHYLBUT-2-EN-1-YL)-9H-PURIN-6-AMINE increases the expression of Tumor necrosis factor alpha-induced protein 2 (TNFAIP2). [19]
------------------------------------------------------------------------------------
⏷ Show the Full List of 28 Drug(s)
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 necrosis factor alpha-induced protein 2 (TNFAIP2). [27]
------------------------------------------------------------------------------------

References

1 KLF5 promotes breast cancer proliferation, migration and invasion in part by upregulating the transcription of TNFAIP2.Oncogene. 2016 Apr 21;35(16):2040-51. doi: 10.1038/onc.2015.263. Epub 2015 Jul 20.
2 Downregulation of TNFAIP2 suppresses proliferation and metastasis in esophageal squamous cell carcinoma through activation of the Wnt/-catenin signaling pathway.Oncol Rep. 2017 May;37(5):2920-2928. doi: 10.3892/or.2017.5557. Epub 2017 Apr 5.
3 The miR-184 binding-site rs8126 T>C polymorphism in TNFAIP2 is associated with risk of gastric cancer.PLoS One. 2013 May 28;8(5):e64973. doi: 10.1371/journal.pone.0064973. Print 2013.
4 MicroRNA-184 inhibits cell proliferation and invasion, and specifically targets TNFAIP2 in Glioma.J Exp Clin Cancer Res. 2015 Mar 26;34(1):27. doi: 10.1186/s13046-015-0142-9.
5 A functional TNFAIP2 3'-UTR rs8126 genetic polymorphism contributes to risk of esophageal squamous cell carcinoma.PLoS One. 2014 Nov 10;9(11):e109318. doi: 10.1371/journal.pone.0109318. eCollection 2014.
6 A functional variant at the miR-184 binding site in TNFAIP2 and risk of squamous cell carcinoma of the head and neck.Carcinogenesis. 2011 Nov;32(11):1668-74. doi: 10.1093/carcin/bgr209. Epub 2011 Sep 20.
7 NF-B-mediated transcriptional upregulation of TNFAIP2 by the Epstein-Barr virus oncoprotein, LMP1, promotes cell motility in nasopharyngeal carcinoma.Oncogene. 2014 Jul 10;33(28):3648-59. doi: 10.1038/onc.2013.345. Epub 2013 Aug 26.
8 TNFAIP2 expression induces epithelial-to-mesenchymal transition and confers platinum resistance in urothelial cancer cells.Lab Invest. 2019 Nov;99(11):1702-1713. doi: 10.1038/s41374-019-0285-y. Epub 2019 Jul 1.
9 Identification of B94 (TNFAIP2) as a potential retinoic acid target gene in acute promyelocytic leukemia.Cancer Res. 2000 Apr 1;60(7):1824-9.
10 Utilization of the human genome sequence localizes human papillomavirus type 16 DNA integrated into the TNFAIP2 gene in a fatal cervical cancer from a 39-year-old woman.Clin Cancer Res. 2002 Feb;8(2):549-54.
11 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
12 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.
13 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
14 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
15 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
16 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
17 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.
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 Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65.
20 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
21 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
22 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
23 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
24 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
25 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
26 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.
27 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
28 BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
29 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
30 Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
31 Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect. 2007 Oct;115(10):1460-6. doi: 10.1289/ehp.10180.
32 Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
33 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
34 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
35 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.