Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZA7MR)

• DOT Name: Perilipin-3 (PLIN3)
• Synonyms: 47 kDa mannose 6-phosphate receptor-binding protein; 47 kDa MPR-binding protein; Cargo selection protein TIP47; Mannose-6-phosphate receptor-binding protein 1; Placental protein 17; PP17
• Gene Name: PLIN3
• Related Disease:
  Fatty liver disease
  Hepatitis C virus infection
  Non-alcoholic fatty liver disease
  Obesity
  Adrenoleukodystrophy
  Clear cell renal carcinoma
  Kidney cancer
  Renal carcinoma
  Renal cell carcinoma
  Cervical carcinoma
  Lung carcinoma
• UniProt ID: PLIN3_HUMAN
• Pfam ID: PF03036
• Sequence:
  MSADGAEADGSTQVTVEEPVQQPSVVDRVASMPLISSTCDMVSAAYASTKESYPHIKTVC
  DAAEKGVRTLTAAAVSGAQPILSKLEPQIASASEYAHRGLDKLEENLPILQQPTEKVLAD
  TKELVSSKVSGAQEMVSSAKDTVATQLSEAVDATRGAVQSGVDKTKSVVTGGVQSVMGSR
  LGQMVLSGVDTVLGKSEEWADNHLPLTDAELARIATSLDGFDVASVQQQRQEQSYFVRLG
  SLSERLRQHAYEHSLGKLRATKQRAQEALLQLSQVLSLMETVKQGVDQKLVEGQEKLHQM
  WLSWNQKQLQGPEKEPPKPEQVESRALTMFRDIAQQLQATCTSLGSSIQGLPTNVKDQVQ
  QARRQVEDLQATFSSIHSFQDLSSSILAQSRERVASAREALDHMVEYVAQNTPVTWLVGP
  FAPGITEKAPEEKK
• Function: Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets. Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network.
• Reactome Pathway:
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  Lipophagy (R-HSA-9613354)
  Chaperone Mediated Autophagy (R-HSA-9613829)
  Late endosomal microautophagy (R-HSA-9615710)
  RHOBTB3 ATPase cycle (R-HSA-9706019)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fatty liver disease	DIS485QZ	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[2]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[3]
Obesity	DIS47Y1K	Strong	Biomarker	[4]
Adrenoleukodystrophy	DISTUD1F	moderate	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[6]
Kidney cancer	DISBIPKM	moderate	Biomarker	[6]
Renal carcinoma	DISER9XT	moderate	Biomarker	[6]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[6]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[7]
Lung carcinoma	DISTR26C	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Perilipin-3 (PLIN3) affects the response to substance of Fluorouracil.	[24]

15 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 Perilipin-3 (PLIN3).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Perilipin-3 (PLIN3).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Perilipin-3 (PLIN3).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Perilipin-3 (PLIN3).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Perilipin-3 (PLIN3).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Perilipin-3 (PLIN3).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Perilipin-3 (PLIN3).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Perilipin-3 (PLIN3).	[13]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Perilipin-3 (PLIN3).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Perilipin-3 (PLIN3).	[17]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Perilipin-3 (PLIN3).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Perilipin-3 (PLIN3).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Perilipin-3 (PLIN3).	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Perilipin-3 (PLIN3).	[22]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Perilipin-3 (PLIN3).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Perilipin-3 (PLIN3).	[20]

References

• [1] The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis.J Lipid Res. 2017 Feb;58(2):420-432. doi: 10.1194/jlr.M073734. Epub 2016 Dec 10.
• [2] miR-148a and miR-30a limit HCV-dependent suppression of the lipid droplet protein, ADRP, in HCV infected cell models.J Med Virol. 2017 Apr;89(4):653-659. doi: 10.1002/jmv.24677. Epub 2016 Sep 20.
• [3] Oleic acid-induced perilipin 5 expression and lipid droplets formation are regulated by the PI3K/PPAR pathway in HepG2 cells.Appl Physiol Nutr Metab. 2019 Aug;44(8):840-848. doi: 10.1139/apnm-2018-0729. Epub 2019 Jul 5.
• [4] The role of perilipin in human obesity and insulin resistance.Curr Opin Lipidol. 2007 Apr;18(2):152-6. doi: 10.1097/MOL.0b013e328086aeab.
• [5] Plin3 protects against alcoholic liver injury by facilitating lipid export from the endoplasmic reticulum.J Cell Biochem. 2019 Sep;120(9):16075-16087. doi: 10.1002/jcb.28889. Epub 2019 May 22.
• [6] PLIN3 is up-regulated and correlates with poor prognosis in clear cell renal cell carcinoma.Urol Oncol. 2018 Jul;36(7):343.e9-343.e19. doi: 10.1016/j.urolonc.2018.04.006.
• [7] Overexpression of placental tissue protein 17b/TIP47 in cervical dysplasias and cervical carcinoma.Anticancer Res. 2001 Jan-Feb;21(1B):639-42.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [19] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.