Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC1AM7S)

• DOT Name: Squamous cell carcinoma antigen recognized by T-cells 3 (SART3)
• Synonyms: SART-3; Tat-interacting protein of 110 kDa; Tip110; p110 nuclear RNA-binding protein
• Gene Name: SART3
• Related Disease:
  B-cell lymphoma
  OPTN-related open angle glaucoma
  Acute myocardial infarction
  Adult T-cell leukemia/lymphoma
  Alzheimer disease
  Bipolar disorder
  Bladder cancer
  Bone disease
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colitis
  Colon cancer
  Colorectal neoplasm
  Hepatitis C virus infection
  Lung cancer
  Lung carcinoma
  Multiple sclerosis
  Neuroblastoma
  Neuromyelitis optica
  Non-small-cell lung cancer
  Plasma cell myeloma
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Seminoma
  T-cell leukaemia
  Zika virus infection
  Disseminated superficial actinic porokeratosis
  Melanoma
  Non-insulin dependent diabetes
  Optic neuritis
  Type-1 diabetes
  Adult lymphoma
  Anxiety
  Anxiety disorder
  Cardiomyopathy
  Hepatocellular carcinoma
  Lymphoma
  Malignant soft tissue neoplasm
  Parkinson disease
  Pediatric lymphoma
  Primary cutaneous T-cell lymphoma
  Sarcoma
  Thyroid gland papillary carcinoma
  Type-1/2 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: SART3_HUMAN
• PDB ID: 2DO4; 5CTQ; 5CTR; 5CTT; 5JJW; 5JJX; 5JPZ; 7XX8; 7XX9
• Pfam ID: PF16605 ; PF05391 ; PF00076
• Sequence:
  MATAAETSASEPEAESKAGPKADGEEDEVKAARTRRKVLSRAVAAATYKTMGPAWDQQEE
  GVSESDGDEYAMASSAESSPGEYEWEYDEEEEKNQLEIERLEEQLSINVYDYNCHVDLIR
  LLRLEGELTKVRMARQKMSEIFPLTEELWLEWLHDEISMAQDGLDREHVYDLFEKAVKDY
  ICPNIWLEYGQYSVGGIGQKGGLEKVRSVFERALSSVGLHMTKGLALWEAYREFESAIVE
  AARLEKVHSLFRRQLAIPLYDMEATFAEYEEWSEDPIPESVIQNYNKALQQLEKYKPYEE
  ALLQAEAPRLAEYQAYIDFEMKIGDPARIQLIFERALVENCLVPDLWIRYSQYLDRQLKV
  KDLVLSVHNRAIRNCPWTVALWSRYLLAMERHGVDHQVISVTFEKALNAGFIQATDYVEI
  WQAYLDYLRRRVDFKQDSSKELEELRAAFTRALEYLKQEVEERFNESGDPSCVIMQNWAR
  IEARLCNNMQKARELWDSIMTRGNAKYANMWLEYYNLERAHGDTQHCRKALHRAVQCTSD
  YPEHVCEVLLTMERTEGSLEDWDIAVQKTETRLARVNEQRMKAAEKEAALVQQEEEKAEQ
  RKRARAEKKALKKKKKIRGPEKRGADEDDEKEWGDDEEEQPSKRRRVENSIPAAGETQNV
  EVAAGPAGKCAAVDVEPPSKQKEKAASLKRDMPKVLHDSSKDSITVFVSNLPYSMQEPDT
  KLRPLFEACGEVVQIRPIFSNRGDFRGYCYVEFKEEKSALQALEMDRKSVEGRPMFVSPC
  VDKSKNPDFKVFRYSTSLEKHKLFISGLPFSCTKEELEEICKAHGTVKDLRLVTNRAGKP
  KGLAYVEYENESQASQAVMKMDGMTIKENIIKVAISNPPQRKVPEKPETRKAPGGPMLLP
  QTYGARGKGRTQLSLLPRALQRPSAAAPQAENGPAAAPAVAAPAATEAPKMSNADFAKLF
  LRK
• Function: U6 snRNP-binding protein that functions as a recycling factor of the splicing machinery. Promotes the initial reassembly of U4 and U6 snRNPs following their ejection from the spliceosome during its maturation. Also binds U6atac snRNPs and may function as a recycling factor for U4atac/U6atac spliceosomal snRNP, an initial step in the assembly of U12-type spliceosomal complex. The U12-type spliceosomal complex plays a role in the splicing of introns with non-canonical splice sites. May also function as a substrate-targeting factor for deubiquitinases like USP4 and USP15. Recruits USP4 to ubiquitinated PRPF3 within the U4/U5/U6 tri-snRNP complex, promoting PRPF3 deubiquitination and thereby regulating the spliceosome U4/U5/U6 tri-snRNP spliceosomal complex disassembly. May also recruit the deubiquitinase USP15 to histone H2B and mediate histone deubiquitination, thereby regulating gene expression and/or DNA repair. May play a role in hematopoiesis probably through transcription regulation of specific genes including MYC; Regulates Tat transactivation activity through direct interaction. May be a cellular factor for HIV-1 gene expression and viral replication.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Definitive	Biomarker	[1]
OPTN-related open angle glaucoma	DISDR98A	Definitive	Biomarker	[2]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[3]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Biomarker	[7]
Bone disease	DISE1F82	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[9]
Colitis	DISAF7DD	Strong	Genetic Variation	[10]
Colon cancer	DISVC52G	Strong	Altered Expression	[11]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[12]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[13]
Lung cancer	DISCM4YA	Strong	Altered Expression	[14]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[14]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[15]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[16]
Neuromyelitis optica	DISBFGKL	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[18]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[19]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[20]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[20]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Seminoma	DIS3J8LJ	Strong	Altered Expression	[22]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[4]
Zika virus infection	DISQUCTY	Strong	Biomarker	[23]
Disseminated superficial actinic porokeratosis	DISELZ77	Moderate	Autosomal dominant	[24]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[25]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[26]
Optic neuritis	DISDYCHC	Disputed	Biomarker	[17]
Type-1 diabetes	DIS7HLUB	Disputed	Biomarker	[27]
Adult lymphoma	DISK8IZR	Limited	Genetic Variation	[28]
Anxiety	DISIJDBA	Limited	Biomarker	[29]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[29]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[30]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[31]
Lymphoma	DISN6V4S	Limited	Genetic Variation	[28]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Genetic Variation	[32]
Parkinson disease	DISQVHKL	Limited	Biomarker	[33]
Pediatric lymphoma	DIS51BK2	Limited	Genetic Variation	[28]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Genetic Variation	[28]
Sarcoma	DISZDG3U	Limited	Genetic Variation	[32]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[32]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[34]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[7]

4 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 Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[35]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[39]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[38]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[40]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[41]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[42]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[44]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Squamous cell carcinoma antigen recognized by T-cells 3 (SART3).	[48]

References

• [1] Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.Oncogene. 2017 Jul 20;36(29):4224-4232. doi: 10.1038/onc.2017.90. Epub 2017 Apr 3.
• [2] A comparative study of structural, functional and circulatory parameters in glaucoma diagnostics.PLoS One. 2018 Aug 23;13(8):e0201599. doi: 10.1371/journal.pone.0201599. eCollection 2018.
• [3] Protective effects of PI3KCG gene on acute myocardial infarction.J Thorac Dis. 2018 Feb;10(2):941-953. doi: 10.21037/jtd.2018.01.59.
• [4] Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product: implications for viral latency.Mol Cell Biol. 1994 Feb;14(2):1374-82. doi: 10.1128/mcb.14.2.1374-1382.1994.
• [5] Electrophysiological evidence of altered facial expressions recognition in Alzheimer's disease: A comprehensive ERP study.Clin Neurophysiol. 2019 Oct;130(10):1813-1824. doi: 10.1016/j.clinph.2019.06.229. Epub 2019 Jul 12.
• [6] Systematic review of cognitive event related potentials in euthymic bipolar disorder.Clin Neurophysiol. 2018 Sep;129(9):1854-1865. doi: 10.1016/j.clinph.2018.05.025. Epub 2018 Jun 27.
• [7] p85 Inactivates MMP-2 and Suppresses Bladder Cancer Invasion by Inhibiting MMP-14 Transcription and TIMP-2 Degradation.Neoplasia. 2019 Sep;21(9):908-920. doi: 10.1016/j.neo.2019.07.007. Epub 2019 Aug 8.
• [8] NF-kappaB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism.J Clin Invest. 2009 Oct;119(10):3024-34. doi: 10.1172/JCI38716. Epub 2009 Sep 21.
• [9] Opposing roles of Nfkb2 gene products p100 and p52 in the regulation of breast cancer stem cells. Breast Cancer Res Treat. 2017 Apr;162(3):465-477. doi: 10.1007/s10549-017-4149-0. Epub 2017 Feb 11.
• [10] Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model.Biomed Pharmacother. 2017 Jan;85:687-696. doi: 10.1016/j.biopha.2016.11.080. Epub 2016 Dec 7.
• [11] SND1, a component of RNA-induced silencing complex, is up-regulated in human colon cancers and implicated in early stage colon carcinogenesis.Cancer Res. 2007 Oct 1;67(19):9568-76. doi: 10.1158/0008-5472.CAN-06-2707.
• [12] Expression of tumor rejection antigens in colorectal carcinomas.Cancer. 2002 Mar 15;94(6):1636-41. doi: 10.1002/cncr.10421.
• [13] The ribonuclease L-dependent antiviral roles of human 2',5'-oligoadenylate synthetase family members against hepatitis C virus.FEBS Lett. 2013 Jan 16;587(2):156-64. doi: 10.1016/j.febslet.2012.11.010. Epub 2012 Nov 26.
• [14] p100 functions as a metastasis activator and is targeted by tumor suppressing microRNA-320a in lung cancer.Thorac Cancer. 2018 Jan;9(1):152-158. doi: 10.1111/1759-7714.12564. Epub 2017 Nov 21.
• [15] Relationship between thiol-disulphide homeostasis and visual evoked potentials in patients with multiple sclerosis.Neurol Sci. 2019 Feb;40(2):385-391. doi: 10.1007/s10072-018-3660-3. Epub 2018 Dec 1.
• [16] Expression of mdr1/P-glycoprotein and p110 in neuroblastoma.J Pathol. 1995 Jan;175(1):13-22. doi: 10.1002/path.1711750104.
• [17] Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders.Neurology. 2020 Jan 28;94(4):e407-e418. doi: 10.1212/WNL.0000000000008684. Epub 2019 Dec 3.
• [18] The RNA-binding protein SART3 promotes miR-34a biogenesis and G(1) cell cycle arrest in lung cancer cells.J Biol Chem. 2019 Nov 15;294(46):17188-17196. doi: 10.1074/jbc.AC119.010419. Epub 2019 Oct 16.
• [19] The effect of marrow stromal cells on TRAF6 expression levels in myeloma cells.Oncol Lett. 2017 Aug;14(2):1464-1470. doi: 10.3892/ol.2017.6322. Epub 2017 Jun 6.
• [20] Loss of negative feedback control of nuclear factor-kappaB2 activity in lymphocytes leads to fatal lung inflammation.Am J Pathol. 2010 Jun;176(6):2646-57. doi: 10.2353/ajpath.2010.090751. Epub 2010 Apr 2.
• [21] Capability of SART3(109-118) peptide to induce cytotoxic T lymphocytes from prostate cancer patients with HLA class I-A11, -A31 and -A33 alleles.Int J Oncol. 2009 Feb;34(2):529-36.
• [22] Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas.Am J Pathol. 2000 Nov;157(5):1597-604. doi: 10.1016/S0002-9440(10)64797-9.
• [23] Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR.J Biol Chem. 2019 Nov 29;294(48):18168-18180. doi: 10.1074/jbc.RA119.009113. Epub 2019 Oct 21.
• [24] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [25] Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma.Mol Cancer. 2018 Aug 17;17(1):124. doi: 10.1186/s12943-018-0868-z.
• [26] Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications.Redox Biol. 2017 Apr;11:637-645. doi: 10.1016/j.redox.2017.01.013. Epub 2017 Jan 16.
• [27] Neurophysiological Evidence for a Compensatory Activity during a Simple Oddball Task in Adolescents with Type 1 Diabetes Mellitus.J Diabetes Res. 2018 Jul 8;2018:8105407. doi: 10.1155/2018/8105407. eCollection 2018.
• [28] Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes.Oncogene. 2000 Mar 2;19(10):1334-45. doi: 10.1038/sj.onc.1203432.
• [29] A Rodent Model of Anxiety: The Effect of Perinatal Immune Challenges on Gastrointestinal Inflammation and Integrity.Neuroimmunomodulation. 2018;25(3):163-175. doi: 10.1159/000493320. Epub 2018 Nov 9.
• [30] Drp1/Fis1 interaction mediates mitochondrial dysfunction in septic cardiomyopathy.J Mol Cell Cardiol. 2019 May;130:160-169. doi: 10.1016/j.yjmcc.2019.04.006. Epub 2019 Apr 11.
• [31] ADAR1 p110 Enhances Adhesion of Tumor Cells to Extracellular Matrix in Hepatocellular Carcinoma via Up-Regulating ITGA2 Expression.Med Sci Monit. 2019 Feb 24;25:1469-1479. doi: 10.12659/MSM.911944.
• [32] Genetic alterations in the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways in the follicular variant of papillary thyroid carcinoma.Cancer. 2010 Jun 15;116(12):2974-83. doi: 10.1002/cncr.25061.
• [33] A novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity.J Cell Sci. 2013 Feb 1;126(Pt 3):789-802. doi: 10.1242/jcs.114439. Epub 2012 Dec 13.
• [34] Pattern Visual Evoked Potential Changes in Diabetic Patients without Retinopathy.J Ophthalmol. 2017;2017:8597629. doi: 10.1155/2017/8597629. Epub 2017 Mar 14.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] 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.
• [39] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [40] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [41] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [42] 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.
• [43] 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.
• [44] 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.
• [45] 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.
• [46] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [47] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [48] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.