Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4XBZC9)

• DOT Name: Basic leucine zipper transcriptional factor ATF-like 2 (BATF2)
• Synonyms: B-ATF-2; Suppressor of AP-1 regulated by IFN; SARI
• Gene Name: BATF2
• Related Disease:
  Colitis
  Gastric cancer
  Pneumonia
  Respiratory disease
  Respiratory syncytial virus infection
  Stomach cancer
  Anxiety
  Anxiety disorder
  Colorectal carcinoma
  Depression
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Metastatic malignant neoplasm
  Mixed anxiety and depressive disorder
  Mycobacterium infection
  Non-small-cell lung cancer
  Tuberculosis
  Adult glioblastoma
  Glioblastoma multiforme
  Influenza
  Pharyngitis
  Advanced cancer
• UniProt ID: BATF2_HUMAN
• Pfam ID: PF00170
• Sequence:
  MHLCGGNGLLTQTDPKEQQRQLKKQKNRAAAQRSRQKHTDKADALHQQHESLEKDNLALR
  KEIQSLQAELAWWSRTLHVHERLCPMDCASCSAPGLLGCWDQAEGLLGPGPQGQHGCREQ
  LELFQTPGSCYPAQPLSPGPQPHDSPSLLQCPLPSLSLGPAVVAEPPVQLSPSPLLFASH
  TGSSLQGSSSKLSALQPSLTAQTAPPQPLELEHPTRGKLGSSPDNPSSALGLARLQSREH
  KPALSAATWQGLVVDPSPHPLLAFPLLSSAQVHF
• Function: AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system. Following infection, participates in the differentiation of CD8(+) thymic conventional dendritic cells in the immune system. 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. Selectively suppresses CCN1 transcription and hence blocks the downstream cell proliferation signals produced by CCN1 and inhibits CCN1-induced anchorage-independent growth and invasion in several cancer types, such as breast cancer, malignant glioma and metastatic melanoma. Possibly acts by interfering with AP-1 binding to CCN1 promoter.
• KEGG Pathway: PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colitis	DISAF7DD	Definitive	Biomarker	[1]
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[2]
Pneumonia	DIS8EF3M	Definitive	Biomarker	[3]
Respiratory disease	DISGGAGJ	Definitive	Genetic Variation	[3]
Respiratory syncytial virus infection	DIS7FWHY	Definitive	Biomarker	[3]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[2]
Anxiety	DISIJDBA	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Depression	DIS3XJ69	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[7]
Lung cancer	DISCM4YA	Strong	Biomarker	[8]
Lung carcinoma	DISTR26C	Strong	Biomarker	[8]
Melanoma	DIS1RRCY	Strong	Biomarker	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[8]
Mixed anxiety and depressive disorder	DISV809X	Strong	Biomarker	[4]
Mycobacterium infection	DISNSMUD	Strong	Biomarker	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[8]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[11]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[12]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[12]
Influenza	DIS3PNU3	moderate	Biomarker	[13]
Pharyngitis	DISSN548	moderate	Biomarker	[14]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[1]

1 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 Basic leucine zipper transcriptional factor ATF-like 2 (BATF2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2).	[17]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2).	[18]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2).	[19]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Basic leucine zipper transcriptional factor ATF-like 2 (BATF2).	[20]

References

• [1] SARI suppresses colitis-associated cancer development by maintaining MCP-1-mediated tumour-associated macrophage recruitment.J Cell Mol Med. 2020 Jan;24(1):189-201. doi: 10.1111/jcmm.14699. Epub 2019 Oct 2.
• [2] BATF2 inhibits chemotherapy resistance by suppressing AP-1 in vincristine-resistant gastric cancer cells.Cancer Chemother Pharmacol. 2019 Dec;84(6):1279-1288. doi: 10.1007/s00280-019-03958-4. Epub 2019 Sep 23.
• [3] Evaluation of case definitions to detect respiratory syncytial virus infection in hospitalized children below 5 years in Rural Western Kenya, 2009-2013.BMC Infect Dis. 2016 May 21;16:218. doi: 10.1186/s12879-016-1532-0.
• [4] Family contributions to sport performance and their utility in predicting appropriate referrals to mental health optimization programmes.Eur J Sport Sci. 2019 Aug;19(7):972-982. doi: 10.1080/17461391.2019.1574906. Epub 2019 Feb 8.
• [5] Calycosin suppresses TGF--induced epithelial-to-mesenchymal transition and migration by upregulating BATF2 to target PAI-1 via the Wnt and PI3K/Akt signaling pathways in colorectal cancer cells.J Exp Clin Cancer Res. 2019 Jun 7;38(1):240. doi: 10.1186/s13046-019-1243-7.
• [6] Decreased expression of BATF2 is associated with a poor prognosis in hepatocellular carcinoma.Int J Cancer. 2011 Feb 15;128(4):771-7. doi: 10.1002/ijc.25407.
• [7] The function of SARI in modulating epithelial-mesenchymal transition and lung adenocarcinoma metastasis.PLoS One. 2012;7(9):e38046. doi: 10.1371/journal.pone.0038046. Epub 2012 Sep 26.
• [8] Decreased SARI expression predicts poor prognosis of Chinese patients with non-small cell lung cancer.Int J Clin Exp Pathol. 2013 Sep 15;6(10):2056-63. eCollection 2013.
• [9] Novel mechanism of MDA-7/IL-24 cancer-specific apoptosis through SARI induction.Cancer Res. 2014 Jan 15;74(2):563-74. doi: 10.1158/0008-5472.CAN-13-1062. Epub 2013 Nov 26.
• [10] Targeting Batf2 for infectious diseases and cancer.Oncotarget. 2015 Sep 29;6(29):26575-82. doi: 10.18632/oncotarget.5576.
• [11] Blood Transcriptomic Stratification of Short-term Risk in Contacts of Tuberculosis.Clin Infect Dis. 2020 Feb 14;70(5):731-737. doi: 10.1093/cid/ciz252.
• [12] Inhibition of Bevacizumab-induced Epithelial-Mesenchymal Transition by BATF2 Overexpression Involves the Suppression of Wnt/-Catenin Signaling in Glioblastoma Cells.Anticancer Res. 2017 Aug;37(8):4285-4294. doi: 10.21873/anticanres.11821.
• [13] Attributable Fraction of Influenza Virus Detection to Mild and Severe Respiratory Illnesses in HIV-Infected and HIV-Uninfected Patients, South Africa, 2012-2016.Emerg Infect Dis. 2017 Jul;23(7):1124-1132. doi: 10.3201/eid2307.161959.
• [14] Validity of clinical case definitions for influenza surveillance among hospitalized patients: results from a rural community in North India.Influenza Other Respir Viruses. 2013 May;7(3):321-9. doi: 10.1111/j.1750-2659.2012.00401.x. Epub 2012 Jul 16.
• [15] 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.
• [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] 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.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] 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.