Details of Drug Off-Target (DOT)

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

• DOT Name: Butyrophilin subfamily 3 member A1 (BTN3A1)
• Synonyms: CD antigen CD277
• Gene Name: BTN3A1
• Related Disease:
  Acute leukaemia
  Advanced cancer
  Colorectal carcinoma
  Major depressive disorder
  Neoplasm
  Schizophrenia
  Epithelial ovarian cancer
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Small-cell lung cancer
• UniProt ID: BT3A1_HUMAN
• PDB ID: 4F80; 4F9L; 4F9P; 4JKW; 4K55; 4N7I; 4N7U; 4V1P; 5HM7; 5LYG; 5LYK; 5ZXK; 6ISM; 6ITA; 6J06; 6XLQ; 8DFX; 8IXV; 8IZE; 8IZG; 8JYC; 8JYE
• Pfam ID: PF13765 ; PF00622 ; PF07686
• Sequence:
  MKMASFLAFLLLNFRVCLLLLQLLMPHSAQFSVLGPSGPILAMVGEDADLPCHLFPTMSA
  ETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIHNVTASD
  SGKYLCYFQDGDFYEKALVELKVAALGSDLHVDVKGYKDGGIHLECRSTGWYPQPQIQWS
  NNKGENIPTVEAPVVADGVGLYAVAASVIMRGSSGEGVSCTIRSSLLGLEKTASISIADP
  FFRSAQRWIAALAGTLPVLLLLLGGAGYFLWQQQEEKKTQFRKKKREQELREMAWSTMKQ
  EQSTRVKLLEELRWRSIQYASRGERHSAYNEWKKALFKPADVILDPKTANPILLVSEDQR
  SVQRAKEPQDLPDNPERFNWHYCVLGCESFISGRHYWEVEVGDRKEWHIGVCSKNVQRKG
  WVKMTPENGFWTMGLTDGNKYRTLTEPRTNLKLPKPPKKVGVFLDYETGDISFYNAVDGS
  HIHTFLDVSFSEALYPVFRILTLEPTALTICPA
• Function: Plays a role in T-cell activation and in the adaptive immune response. Regulates the proliferation of activated T-cells. Regulates the release of cytokines and IFNG by activated T-cells. Mediates the response of T-cells toward infected and transformed cells that are characterized by high levels of phosphorylated metabolites, such as isopentenyl pyrophosphate.
• Tissue Specificity: Detected on T-cells, natural killer cells, dendritic cells and macrophages (at protein level). Ubiquitous. Highly expressed in heart, pancreas and lung, Moderately expressed in placenta, liver and muscle.
• Reactome Pathway: Butyrophilin (BTN) family interactions (R-HSA-8851680)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute leukaemia	DISDQFDI	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[6]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[7]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[6]
Small-cell lung cancer	DISK3LZD	Limited	Genetic Variation	[7]

1 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 Butyrophilin subfamily 3 member A1 (BTN3A1).	[8]

7 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 Butyrophilin subfamily 3 member A1 (BTN3A1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Butyrophilin subfamily 3 member A1 (BTN3A1).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Butyrophilin subfamily 3 member A1 (BTN3A1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Butyrophilin subfamily 3 member A1 (BTN3A1).	[12]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Butyrophilin subfamily 3 member A1 (BTN3A1).	[13]
Epanova	DMHEAGL	Approved	Epanova decreases the expression of Butyrophilin subfamily 3 member A1 (BTN3A1).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Butyrophilin subfamily 3 member A1 (BTN3A1).	[15]

References

• [1] A Case of Acute Myeloid Leukemia with Novel Translocation t(6;11)(p22.2;q23) and Concurrent Insertion ins(11;9)(q23;p21.3p21.3).Adv Exp Med Biol. 2017;1021:93-98. doi: 10.1007/5584_2017_86.
• [2] Evaluating in vivo efficacy - toxicity profile of TEG001 in humanized mice xenografts against primary human AML disease and healthy hematopoietic cells.J Immunother Cancer. 2019 Mar 12;7(1):69. doi: 10.1186/s40425-019-0558-4.
• [3] Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector T cells with antitumor activity.Oncoimmunology. 2017 Jan 6;6(3):e1278099. doi: 10.1080/2162402X.2016.1278099. eCollection 2017.
• [4] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways.Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.
• [5] Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
• [6] CD277 is a negative co-stimulatory molecule universally expressed by ovarian cancer microenvironmental cells.Oncotarget. 2010 Sep;1(5):329-38. doi: 10.18632/oncotarget.165.
• [7] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [8] 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.
• [9] 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.
• [10] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [11] 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.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [14] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [15] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.