Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2DNESG)

DOT Name	Tripartite motif-containing protein 29 (TRIM29)
Synonyms	Ataxia telangiectasia group D-associated protein
Gene Name	TRIM29
Related Disease	Carcinoma of liver and intrahepatic biliary tract ( ) Invasive breast carcinoma ( ) Liver cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Thyroid gland papillary carcinoma ( ) Advanced cancer ( ) Ataxia-telangiectasia ( ) Benign neoplasm ( ) Bladder cancer ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Cervical cancer ( ) Cervical carcinoma ( ) Colorectal carcinoma ( ) Cytomegalovirus infection ( ) Epithelial neoplasm ( ) Estrogen-receptor positive breast cancer ( ) Herpes simplex infection ( ) Matthew-Wood syndrome ( ) Nasopharyngeal carcinoma ( ) Neoplasm ( ) Prostate neoplasm ( ) Squamous cell carcinoma ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Niemann-Pick disease type C ( ) Pancreatic adenocarcinoma ( ) Pancreatic cancer ( ) Pancreatic ductal carcinoma ( ) Stroke ( ) Adenocarcinoma ( ) Bone osteosarcoma ( ) Gastric cancer ( ) Glioma ( ) Hepatocellular carcinoma ( ) Lung cancer ( ) Malignant glioma ( ) Mixed glioma ( ) Non-small-cell lung cancer ( ) Osteosarcoma ( ) Patent ductus arteriosus ( ) Stomach cancer ( ) Thyroid cancer ( ) Thyroid gland carcinoma ( ) Thyroid tumor ( )
UniProt ID	TRI29_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2CSV
Pfam ID	PF00643
Sequence	MEAADASRSNGSSPEARDARSPSGPSGSLENGTKADGKDAKTTNGHGGEAAEGKSLGSAL KPGEGRSALFAGNEWRRPIIQFVESGDDKNSNYFSMDSMEGKRSPYAGLQLGAAKKPPVT FAEKGELRKSIFSESRKPTVSIMEPGETRRNSYPRADTGLFSRSKSGSEEVLCDSCIGNK QKAVKSCLVCQASFCELHLKPHLEGAAFRDHQLLEPIRDFEARKCPVHGKTMELFCQTDQ TCICYLCMFQEHKNHSTVTVEEAKAEKETELSLQKEQLQLKIIEIEDEAEKWQKEKDRIK SFTTNEKAILEQNFRDLVRDLEKQKEEVRAALEQREQDAVDQVKVIMDALDERAKVLHED KQTREQLHSISDSVLFLQEFGALMSNYSLPPPLPTYHVLLEGEGLGQSLGNFKDDLLNVC MRHVEKMCKADLSRNFIERNHMENGGDHRYVNNYTNSFGGEWSAPDTMKRYSMYLTPKGG VRTSYQPSSPGRFTKETTQKNFNNLYGTKGNYTSRVWEYSSSIQNSDNDLPVVQGSSSFS LKGYPSLMRSQSPKAQPQTWKSGKQTMLSHYRPFYVNKGNGIGSNEAP
Function	Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. Mechanistically, TRIM29 interacts with IKBKG/NEMO in the lysosome where it induces its 'Lys-48' ubiquitination and subsequent degradation. In turn, the expression of type I interferons and the production of pro-inflammatory cytokines are inhibited. Additionally, induces the 'Lys-48' ubiquitination of STING1 in a similar way, leading to its degradation.
Tissue Specificity	Expressed in placenta, prostate and thymus.
Reactome Pathway	Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Biomarker	[1]
Invasive breast carcinoma	DISANYTW	Definitive	Biomarker	[2]
Liver cancer	DISDE4BI	Definitive	Biomarker	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Definitive	Altered Expression	[3]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[6]
Benign neoplasm	DISDUXAD	Strong	Altered Expression	[7]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[8]
Cervical cancer	DISFSHPF	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[10]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[11]
Epithelial neoplasm	DIS0T594	Strong	Biomarker	[7]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Altered Expression	[12]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[13]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[14]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Altered Expression	[15]
Neoplasm	DISZKGEW	Strong	Biomarker	[16]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[17]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[7]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[6]
Niemann-Pick disease type C	DIS492ZO	moderate	Altered Expression	[18]
Pancreatic adenocarcinoma	DISKHX7S	moderate	Biomarker	[19]
Pancreatic cancer	DISJC981	moderate	Biomarker	[19]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Altered Expression	[19]
Stroke	DISX6UHX	moderate	Genetic Variation	[20]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[21]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[22]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[23]
Glioma	DIS5RPEH	Limited	Biomarker	[24]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[16]
Lung cancer	DISCM4YA	Limited	Altered Expression	[25]
Malignant glioma	DISFXKOV	Limited	Biomarker	[24]
Mixed glioma	DIS64UY3	Limited	Biomarker	[24]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[21]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[22]
Patent ductus arteriosus	DIS9P8YS	Limited	Biomarker	[26]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[23]
Thyroid cancer	DIS3VLDH	Limited	Altered Expression	[27]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[27]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[27]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tripartite motif-containing protein 29 (TRIM29).	[28]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Tripartite motif-containing protein 29 (TRIM29).	[31]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Tripartite motif-containing protein 29 (TRIM29).	[32]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Tripartite motif-containing protein 29 (TRIM29).	[32]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tripartite motif-containing protein 29 (TRIM29).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tripartite motif-containing protein 29 (TRIM29).	[30]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[33]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[34]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[35]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Tripartite motif-containing protein 29 (TRIM29).	[36]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[37]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Tripartite motif-containing protein 29 (TRIM29).	[36]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[35]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Tripartite motif-containing protein 29 (TRIM29).	[38]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[39]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of Tripartite motif-containing protein 29 (TRIM29).	[40]
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⏷ Show the Full List of 12 Drug(s)

References

1	TRIM29 prevents hepatocellular carcinoma progression by inhibiting Wnt/-catenin signaling pathway.Acta Biochim Biophys Sin (Shanghai). 2019 Jan 1;51(1):68-77. doi: 10.1093/abbs/gmy151.
2	TRIM29 suppresses TWIST1 and invasive breast cancer behavior.Cancer Res. 2014 Sep 1;74(17):4875-87. doi: 10.1158/0008-5472.CAN-13-3579. Epub 2014 Jun 20.
3	TRIM29 as a novel prostate basal cell marker for diagnosis of prostate cancer.Acta Histochem. 2014 Jun;116(5):708-12. doi: 10.1016/j.acthis.2013.12.009. Epub 2014 Jan 30.
4	LncRNA HOXA11-AS accumulation-induced microRNA-761 downregulation regulates cell growth by targeting TRIM29 in papillary thyroid cancer.Am J Transl Res. 2019 Nov 15;11(11):6826-6837. eCollection 2019.
5	Loss of TRIM29 suppresses cancer stem cell-like characteristics of PDACs via accelerating ISG15 degradation.Oncogene. 2020 Jan;39(3):546-559. doi: 10.1038/s41388-019-0992-2. Epub 2019 Sep 9.
6	ATDC mediates a TP63-regulated basal cancer invasive program.Oncogene. 2019 May;38(18):3340-3354. doi: 10.1038/s41388-018-0646-9. Epub 2019 Jan 14.
7	Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma.Cancer Res. 2018 Dec 15;78(24):6795-6806. doi: 10.1158/0008-5472.CAN-18-1495. Epub 2018 Nov 2.
8	The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia.J Biol Chem. 2016 Oct 7;291(41):21541-21552. doi: 10.1074/jbc.M116.730960. Epub 2016 Aug 17.
9	TRIM29 overexpression is associated with poor prognosis and promotes tumor progression by activating Wnt/-catenin pathway in cervical cancer.Oncotarget. 2016 May 10;7(19):28579-91. doi: 10.18632/oncotarget.8686.
10	TRIM29 facilitates the epithelial-to-mesenchymal transition and the progression of colorectal cancer via the activation of the Wnt/-catenin signaling pathway.J Exp Clin Cancer Res. 2019 Feb 27;38(1):104. doi: 10.1186/s13046-019-1098-y.
11	Identification of the E3 Ligase TRIM29 as a Critical Checkpoint Regulator of NK Cell Functions.J Immunol. 2019 Aug 15;203(4):873-880. doi: 10.4049/jimmunol.1900171. Epub 2019 Jul 3.
12	TRIM29 functions as a tumor suppressor in nontumorigenic breast cells and invasive ER+ breast cancer.Am J Pathol. 2012 Feb;180(2):839-47. doi: 10.1016/j.ajpath.2011.10.020. Epub 2011 Dec 2.
13	TRIM29 promotes DNA virus infections by inhibiting innate immune response.Nat Commun. 2017 Oct 16;8(1):945. doi: 10.1038/s41467-017-00101-w.
14	ATDC/TRIM29 phosphorylation by ATM/MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells.Cancer Res. 2014 Mar 15;74(6):1778-88. doi: 10.1158/0008-5472.CAN-13-2289. Epub 2014 Jan 27.
15	MicroRNA?22 acts as tumor suppressor by targeting TRIM29 and blocking the activity of PI3K/AKT signaling in nasopharyngeal carcinoma invitro.Mol Med Rep. 2018 Jun;17(6):8244-8252. doi: 10.3892/mmr.2018.8894. Epub 2018 Apr 19.
16	MicroRNA-424-5p acts as a potential biomarker and inhibits proliferation and invasion in hepatocellular carcinoma by targeting TRIM29.Life Sci. 2019 May 1;224:1-11. doi: 10.1016/j.lfs.2019.03.028. Epub 2019 Mar 12.
17	Marked gene transcript level alterations occur early during radical prostatectomy.Eur Urol. 2008 Feb;53(2):333-44. doi: 10.1016/j.eururo.2007.03.075. Epub 2007 Apr 9.
18	Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway.Oncotarget. 2016 Mar 22;7(12):13634-50. doi: 10.18632/oncotarget.7215.
19	TRIM29 as a novel biomarker in pancreatic adenocarcinoma.Dis Markers. 2014;2014:317817. doi: 10.1155/2014/317817. Epub 2014 Apr 22.
20	A genome-wide association study identifies a gene network of ADAMTS genes in the predisposition to pediatric stroke.Blood. 2012 Dec 20;120(26):5231-6. doi: 10.1182/blood-2012-07-442038. Epub 2012 Sep 18.
21	Significance of TRIM29 and -catenin expression in non-small-cell lung cancer.J Chin Med Assoc. 2012 Jun;75(6):269-74. doi: 10.1016/j.jcma.2012.04.015. Epub 2012 May 31.
22	High expression of TRIM29(ATDC) contributes to poor prognosis and tumor metastasis by inducing epithelialmesenchymal transition in osteosarcoma.Oncol Rep. 2017 Sep;38(3):1645-1654. doi: 10.3892/or.2017.5842. Epub 2017 Jul 21.
23	Prognostic value of tripartite motif containing 29 expression in patients with gastric cancer following surgical resection.Oncol Lett. 2018 Apr;15(4):5792-5798. doi: 10.3892/ol.2018.8059. Epub 2018 Feb 15.
24	ATDC contributes to sustaining the growth and invasion of glioma cells through regulating Wnt/-catenin signaling.Chem Biol Interact. 2019 May 25;305:148-155. doi: 10.1016/j.cbi.2019.03.033. Epub 2019 Mar 29.
25	Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.PLoS One. 2014 Mar 20;9(3):e91805. doi: 10.1371/journal.pone.0091805. eCollection 2014.
26	ATDC is required for the initiation of KRAS-induced pancreatic tumorigenesis.Genes Dev. 2019 Jun 1;33(11-12):641-655. doi: 10.1101/gad.323303.118. Epub 2019 May 2.
27	TRIM29 promotes progression of thyroid carcinoma via activating P13K/AKT signaling pathway.Oncol Rep. 2017 Mar;37(3):1555-1564. doi: 10.3892/or.2017.5364. Epub 2017 Jan 13.
28	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.
29	Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
30	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.
31	Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
32	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.
33	Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
34	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.
35	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
36	Activation of PPAR and inhibition of cell proliferation reduces key proteins associated with the basal subtype of bladder cancer in As3+-transformed UROtsa cells. PLoS One. 2020 Aug 21;15(8):e0237976. doi: 10.1371/journal.pone.0237976. eCollection 2020.
37	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
38	Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
39	Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
40	The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.