Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDHOA74)

• DOT Name: Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL)
• Gene Name: BNIPL
• Related Disease: Hepatocellular carcinoma
• UniProt ID: BNIPL_HUMAN
• Pfam ID: PF12496 ; PF13716
• Sequence:
  MGTIQEAGKKTDVGVREIAEAPELGAALRHGELELKEEWQDEEFPRLLPEEAGTSEDPED
  PKGDSQAAAGTPSTLALCGQRPMRKRLSAPELRLSLTKGPGNDGASPTQSAPSSPDGSSD
  LEIDELETPSDSEQLDSGHEFEWEDELPRAEGLGTSETAERLGRGCMWDVTGEDGHHWRV
  FRMGPREQRVDMTVIEPYKKVLSHGGYHGDGLNAVILFASCYLPRSSIPNYTYVMEHLFR
  YMVGTLELLVAENYLLVHLSGGTSRAQVPPLSWIRQCYRTLDRRLRKNLRALVVVHATWY
  VKAFLALLRPFISSKFTRKIRFLDSLGELAQLISLDQVHIPEAVRQLDRDLHGSGGT
• Function: May be a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death.
• Tissue Specificity: Isoform 2 is expressed in placenta and lung.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]

2 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 Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein (BNIPL).	[7]

References

• [1] cDNA expression array analysis of gene expression in human hepatocarcinoma Hep3B cells induced by BNIPL-1.Acta Biochim Biophys Sin (Shanghai). 2005 Sep;37(9):618-24. doi: 10.1111/j.1745-7270.2005.00086.x.
• [2] 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.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.