Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI61WXQ)

• DOT Name: Basic leucine zipper transcriptional factor ATF-like 3 (BATF3)
• Synonyms: B-ATF-3; 21 kDa small nuclear factor isolated from T-cells; Jun dimerization protein p21SNFT
• Gene Name: BATF3
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Fatty liver disease
  Glioma
  Inflammatory bowel disease
  Leprosy
  Malignant soft tissue neoplasm
  Neoplasm
  Sarcoma
  B-cell neoplasm
  Bacterial infection
  Colorectal carcinoma
  Lymphoma
  Advanced cancer
  Anaplastic large cell lymphoma
  Classic Hodgkin lymphoma
  Melanoma
  Schistosomiasis
• UniProt ID: BATF3_HUMAN
• Pfam ID: PF00170
• Sequence:
  MSQGLPAAGSVLQRSVAAPGNQPQPQPQQQSPEDDDRKVRRREKNRVAAQRSRKKQTQKA
  DKLHEEYESLEQENTMLRREIGKLTEELKHLTEALKEHEKMCPLLLCPMNFVPVPPRPDP
  VAGCLPR
• Function: AP-1 family transcription factor that controls the differentiation of CD8(+) thymic conventional dendritic cells in the immune system. Required for development of CD8-alpha(+) classical dendritic cells (cDCs) and related CD103(+) dendritic cells that cross-present antigens to CD8 T-cells and produce interleukin-12 (IL12) in response to pathogens. Acts via the formation of a heterodimer with JUN family proteins that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3' and regulates expression of target genes.
• KEGG Pathway: PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[5]
Leprosy	DISAA4UI	Strong	Biomarker	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[8]
Sarcoma	DISZDG3U	Strong	Biomarker	[7]
B-cell neoplasm	DISVY326	moderate	Biomarker	[9]
Bacterial infection	DIS5QJ9S	moderate	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	moderate	Altered Expression	[11]
Lymphoma	DISN6V4S	moderate	Biomarker	[9]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[12]
Anaplastic large cell lymphoma	DISP4D1R	Limited	Biomarker	[9]
Classic Hodgkin lymphoma	DISV1LU6	Limited	Biomarker	[9]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[13]
Schistosomiasis	DIS6PD44	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[19]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[23]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[24]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Basic leucine zipper transcriptional factor ATF-like 3 (BATF3).	[25]

References

• [1] JDP1 (DNAJC12/Hsp40) expression in breast cancer and its association with estrogen receptor status.Int J Mol Med. 2006 Feb;17(2):363-7.
• [2] Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells.Sci Immunol. 2017 May 19;2(11):eaal1713. doi: 10.1126/sciimmunol.aal1713.
• [3] Murine CD103(+) dendritic cells protect against steatosis progression towards steatohepatitis.J Hepatol. 2017 Jun;66(6):1241-1250. doi: 10.1016/j.jhep.2017.01.008. Epub 2017 Jan 18.
• [4] Upregulation of circular RNA circ_0034642 indicates unfavorable prognosis in glioma and facilitates cell proliferation and invasion via the miR-1205/BATF3 axis.J Cell Biochem. 2019 Aug;120(8):13737-13744. doi: 10.1002/jcb.28646. Epub 2019 Apr 2.
• [5] The transcription factor Batf3 inhibits the differentiation of regulatory T cells in the periphery.Exp Mol Med. 2017 Nov 17;49(11):e393. doi: 10.1038/emm.2017.157.
• [6] Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.Nat Genet. 2015 Mar;47(3):267-71. doi: 10.1038/ng.3212. Epub 2015 Feb 2.
• [7] Batf3-Dependent Genes Control Tumor Rejection Induced by Dendritic Cells Independently of Cross-Presentation.Cancer Immunol Res. 2019 Jan;7(1):29-39. doi: 10.1158/2326-6066.CIR-18-0138. Epub 2018 Nov 27.
• [8] Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity.J Exp Med. 2019 Jun 3;216(6):1359-1376. doi: 10.1084/jem.20180660. Epub 2019 Apr 18.
• [9] Ectopic expression of transcription factor BATF3 induces B-cell lymphomas in a murine B-cell transplantation model.Oncotarget. 2018 Mar 23;9(22):15942-15951. doi: 10.18632/oncotarget.24639. eCollection 2018 Mar 23.
• [10] A Batf3/Nlrp3/IL-18 Axis Promotes Natural Killer Cell IL-10 Production during Listeria monocytogenes Infection.Cell Rep. 2018 May 29;23(9):2582-2594. doi: 10.1016/j.celrep.2018.04.106.
• [11] MiR-760 suppresses human colorectal cancer growth by targeting BATF3/AP-1/cyclinD1 signaling.J Exp Clin Cancer Res. 2018 Apr 16;37(1):83. doi: 10.1186/s13046-018-0757-8.
• [12] Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics.J Immunother Cancer. 2019 Jan 9;7(1):6. doi: 10.1186/s40425-018-0495-7.
• [13] The Expression Quantitative Trait Loci in Immune Pathways and their Effect on Cutaneous Melanoma Prognosis.Clin Cancer Res. 2016 Jul 1;22(13):3268-80. doi: 10.1158/1078-0432.CCR-15-2066. Epub 2016 Jan 5.
• [14] Absence of Batf3 results in reduced liver pathology in mice infected with Schistosoma japonicum.Parasit Vectors. 2017 Jun 24;10(1):306. doi: 10.1186/s13071-017-2250-1.
• [15] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [16] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [17] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [23] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [24] 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.
• [25] 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.