Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7USYCY)

• DOT Name: Vesicle transport protein SEC20 (BNIP1)
• Synonyms: BCL2/adenovirus E1B 19 kDa protein-interacting protein 1; Transformation-related gene 8 protein; TRG-8
• Gene Name: BNIP1
• Related Disease:
  Breast cancer
  Breast carcinoma
  High blood pressure
  Open-angle glaucoma
  Cervical carcinoma
  Amyotrophic lateral sclerosis
  Frontotemporal dementia
  Progressive supranuclear palsy
• UniProt ID: SEC20_HUMAN
• Pfam ID: PF03908
• Sequence:
  MAAPQDVHVRICNQEIVKFDLEVKALIQDIRDCSGPLSALTELNTKVKEKFQQLRHRIQD
  LEQLAKEQDKESEKQLLLQEVENHKKQMLSNQASWRKANLTCKIAIDNLEKAELLQGGDL
  LRQRKTTKESLAQTSSTITESLMGISRMMAQQVQQSEEAMQSLVTSSRTILDANEEFKSM
  SGTIQLGRKLITKYNRRELTDKLLIFLALALFLATVLYIVKKRLFPFL
• Function: As part of a SNARE complex may be involved in endoplasmic reticulum membranes fusion and be required for the maintenance of endoplasmic reticulum organization. Also plays a role in apoptosis. It is for instance required for endoplasmic reticulum stress-induced apoptosis. As a substrate of RNF185 interacting with SQSTM1, might also be involved in mitochondrial autophagy (Probable).
• Tissue Specificity: Isoform 1 is highly expressed in heart, brain, liver skeletal muscle and pancreas. Isoform 3 is moderately expressed in placenta, lung and kidney. Isoform 4 is highly expressed in testis and small intestine.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway: COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)

Molecular Interaction Atlas (MIA) of This DOT

8 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]
High blood pressure	DISY2OHH	Strong	Biomarker	[2]
Open-angle glaucoma	DISSZEE8	Strong	Genetic Variation	[3]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[4]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[5]
Frontotemporal dementia	DISKYHXL	Limited	Genetic Variation	[5]
Progressive supranuclear palsy	DISO5KRQ	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Vesicle transport protein SEC20 (BNIP1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Vesicle transport protein SEC20 (BNIP1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Vesicle transport protein SEC20 (BNIP1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Vesicle transport protein SEC20 (BNIP1).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Vesicle transport protein SEC20 (BNIP1).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Vesicle transport protein SEC20 (BNIP1).	[10]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Vesicle transport protein SEC20 (BNIP1).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Vesicle transport protein SEC20 (BNIP1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Vesicle transport protein SEC20 (BNIP1).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Vesicle transport protein SEC20 (BNIP1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Vesicle transport protein SEC20 (BNIP1).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Vesicle transport protein SEC20 (BNIP1).	[14]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Vesicle transport protein SEC20 (BNIP1).	[15]

References

• [1] NIP1/DUOXA1 expression in epithelial breast cancer cells: regulation of cell adhesion and actin dynamics.Breast Cancer Res Treat. 2010 Feb;119(3):773-86. doi: 10.1007/s10549-009-0372-7. Epub 2009 Mar 26.
• [2] A neural network model for constructing endophenotypes of common complex diseases: an application to male young-onset hypertension microarray data.Bioinformatics. 2009 Apr 15;25(8):981-8. doi: 10.1093/bioinformatics/btp106. Epub 2009 Feb 23.
• [3] A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nat Commun. 2018 Jun 11;9(1):2278. doi: 10.1038/s41467-018-04555-4.
• [4] BNIP1 inhibits cell proliferation, migration and invasion, and promotes apoptosis by mTOR in cervical cancer cells.Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1397-1407. doi: 10.26355/eurrev_201902_17096.
• [5] Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum.JAMA Neurol. 2018 Jul 1;75(7):860-875. doi: 10.1001/jamaneurol.2018.0372.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [10] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [11] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Identification of genes associated with paraquat-induced toxicity in SH-SY5Y cells by PCR array focused on apoptotic pathways. J Toxicol Environ Health A. 2008;71(22):1457-67. doi: 10.1080/15287390802329364.