Details of Drug Off-Target (DOT)

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

• DOT Name: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L)
• Synonyms: Adenovirus E1B19K-binding protein B5; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3A; NIP3-like protein X; NIP3L
• Gene Name: BNIP3L
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Advanced cancer
  Autosomal dominant optic atrophy, classic form
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiac disease
  Cardiac failure
  Congestive heart failure
  Epithelial ovarian cancer
  Essential thrombocythemia
  Leber hereditary optic neuropathy
  Matthew-Wood syndrome
  Myelodysplastic syndrome
  Myocardial infarction
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Pancreatitis
  Parkinson disease
  Schizophrenia
  Triple negative breast cancer
  Ductal breast carcinoma in situ
  Intracerebral hemorrhage
  Mantle cell lymphoma
  Type-1/2 diabetes
  Amyotrophic lateral sclerosis
  Lysosomal storage disease
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
• UniProt ID: BNI3L_HUMAN
• Pfam ID: PF06553
• Sequence:
  MSSHLVEPPPPLHNNNNNCEENEQSLPPPAGLNSSWVELPMNSSNGNDNGNGKNGGLEHV
  PSSSSIHNGDMEKILLDAQHESGQSSSRGSSHCDSPSPQEDGQIMFDVEMHTSRDHSSQS
  EEEVVEGEKEVEALKKSADWVSDWSSRPENIPPKEFHFRHPKRSVSLSMRKSGAMKKGGI
  FSAEFLKVFIPSLFLSHVLALGLGIYIGKRLSTPSASTY
• Function: Induces apoptosis. Interacts with viral and cellular anti-apoptosis proteins. Can overcome the suppressors BCL-2 and BCL-XL, although high levels of BCL-XL expression will inhibit apoptosis. Inhibits apoptosis induced by BNIP3. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. May function as a tumor suppressor.
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway: TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Genetic Variation	[5]
Cardiac disease	DISVO1I5	Strong	Biomarker	[6]
Cardiac failure	DISDC067	Strong	Altered Expression	[7]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[5]
Essential thrombocythemia	DISWWK11	Strong	Altered Expression	[8]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Genetic Variation	[9]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[10]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[11]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[5]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[5]
Pancreatic cancer	DISJC981	Strong	Biomarker	[10]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Biomarker	[14]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[15]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[2]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[16]
Intracerebral hemorrhage	DISC81BT	moderate	Biomarker	[17]
Mantle cell lymphoma	DISFREOV	moderate	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[19]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[20]
Lysosomal storage disease	DIS6QM6U	Limited	Altered Expression	[21]
Prostate cancer	DISF190Y	Limited	Biomarker	[22]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[22]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[22]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L) increases the response to substance of 3R14S-OCHRATOXIN A.	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[29]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[31]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[32]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[33]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[34]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[35]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[37]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[39]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[40]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[41]
Aspirin	DM672AH	Approved	Aspirin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[42]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[43]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[44]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[45]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[46]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[47]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[48]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[48]
Vandetanib	DMRICNP	Approved	Vandetanib increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[49]
Lamivudine	DMI347A	Approved	Lamivudine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[46]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[50]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[51]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[52]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[53]
Clioquinol	DM746BZ	Withdrawn from market	Clioquinol decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[55]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[56]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[58]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[59]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[60]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[61]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[18]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[38]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L).	[54]

References

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