Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3OAAZ4)

• DOT Name: Perilipin-1 (PLIN1)
• Synonyms: Lipid droplet-associated protein
• Gene Name: PLIN1
• Related Disease: PLIN1-related familial partial lipodystrophy
• UniProt ID: PLIN1_HUMAN
• Pfam ID: PF03036
• Sequence:
  MAVNKGLTLLDGDLPEQENVLQRVLQLPVVSGTCECFQKTYTSTKEAHPLVASVCNAYEK
  GVQSASSLAAWSMEPVVRRLSTQFTAANELACRGLDHLEEKIPALQYPPEKIASELKDTI
  STRLRSARNSISVPIASTSDKVLGAALAGCELAWGVARDTAEFAANTRAGRLASGGADLA
  LGSIEKVVEYLLPPDKEESAPAPGHQQAQKSPKAKPSLLSRVGALTNTLSRYTVQTMARA
  LEQGHTVAMWIPGVVPLSSLAQWGASVAMQAVSRRRSEVRVPWLHSLAAAQEEDHEDQTD
  TEGEDTEEEEELETEENKFSEVAALPGPRGLLGGVAHTLQKTLQTTISAVTWAPAAVLGM
  AGRVLHLTPAPAVSSTKGRAMSLSDALKGVTDNVVDTVVHYVPLPRLSLMEPESEFRDID
  NPPAEVERREAERRASGAPSAGPEPAPRLAQPRRSLRSAQSPGAPPGPGLEDEVATPAAP
  RPGFPAVPREKPKRRVSDSFFRPSVMEPILGRTHYSQLRKKS
• Function: Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels.
• Tissue Specificity: Detected in adipocytes from white adipose tissue (at protein level) . Detected in visceral adipose tissue and mammary gland .
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Apelin sig.ling pathway (hsa04371)
  Thermogenesis (hsa04714)
  Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway:
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose (R-HSA-9031528)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
PLIN1-related familial partial lipodystrophy	DISAHT2X	Strong	Autosomal dominant	[1]

10 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 Perilipin-1 (PLIN1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Perilipin-1 (PLIN1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Perilipin-1 (PLIN1).	[4]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Perilipin-1 (PLIN1).	[5]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Perilipin-1 (PLIN1).	[6]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Perilipin-1 (PLIN1).	[7]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Perilipin-1 (PLIN1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Perilipin-1 (PLIN1).	[9]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Perilipin-1 (PLIN1).	[10]
Oleic acid	DM54O1Z	Investigative	Oleic acid increases the expression of Perilipin-1 (PLIN1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Perilipin-1 (PLIN1).	[8]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [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] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [6] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [7] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [8] 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.
• [9] Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease. Food Chem Toxicol. 2014 Aug;70:9-18. doi: 10.1016/j.fct.2014.04.011. Epub 2014 May 1.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [11] A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: application to acetaminophen. Toxicol Appl Pharmacol. 2016 Feb 1;292:40-55.