Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV8G50L)

• DOT Name: Perilipin-5 (PLIN5)
• Synonyms: Lipid storage droplet protein 5
• Gene Name: PLIN5
• Related Disease:
  Advanced cancer
  Metastatic malignant neoplasm
  Non-insulin dependent diabetes
  Arteriosclerosis
  Atherosclerosis
  B-cell neoplasm
  Cardiac failure
  Congestive heart failure
  Fatty liver disease
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Non-alcoholic fatty liver disease
  Obesity
  Prostate cancer
  Prostate carcinoma
  Coronary atherosclerosis
  Myocardial ischemia
  Rhabdomyosarcoma
• UniProt ID: PLIN5_HUMAN
• Pfam ID: PF03036
• Sequence:
  MSEEEAAQIPRSSVWEQDQQNVVQRVVALPLVRATCTAVCDVYSAAKDRHPLLGSACRLA
  ENCVCGLTTRALDHAQPLLEHLQPQLATMNSLACRGLDKLEEKLPFLQQPSETVVTSAKD
  VVASSVTGVVDLARRGRRWSVELKRSVSHAVDVVLEKSEELVDHFLPMTEEELAALAAEA
  EGPEVGSVEDQRRQQGYFVRLGSLSARIRHLAYEHSVGKLRQSKHRAQDTLAQLQETLEL
  IDHMQCGVTPTAPACPGKVHELWGEWGQRPPESRRRSQAELETLVLSRSLTQELQGTVEA
  LESSVRGLPAGAQEKVAEVRRSVDALQTAFADARCFRDVPAAALAEGRGRVAHAHACVDE
  LLELVVQAVPLPWLVGPFAPILVERPEPLPDLADLVDEVIGGPDPRWAHLDWPAQQRAWE
  AEHRDGSGNGDGDRMGVAGDICEQEPETPSCPVKHTLMPELDF
• Function: Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE.
• Tissue Specificity: Expressed in skeletal muscle, liver, heart and kidney.
• KEGG Pathway: PPAR sig.ling pathway (hsa03320)

Molecular Interaction Atlas (MIA) of This DOT

18 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Genetic Variation	[1]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[2]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Cardiac failure	DISDC067	Strong	Biomarker	[5]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[8]
Obesity	DIS47Y1K	Strong	Genetic Variation	[9]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[10]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[10]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[11]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[11]
Rhabdomyosarcoma	DISNR7MS	moderate	Altered Expression	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Perilipin-5 (PLIN5).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Perilipin-5 (PLIN5).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Perilipin-5 (PLIN5).	[15]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Perilipin-5 (PLIN5).	[16]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Perilipin-5 (PLIN5).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Perilipin-5 (PLIN5).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Perilipin-5 (PLIN5).	[19]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 increases the expression of Perilipin-5 (PLIN5).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Perilipin-5 (PLIN5).	[22]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Perilipin-5 (PLIN5).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Perilipin-5 (PLIN5).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Perilipin-5 (PLIN5).	[24]

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 decreases the methylation of Perilipin-5 (PLIN5).	[21]

References

• [1] Redox state of adipose tissue for patients with gastric cancer and its connection with the body mass index and distance from the tumor.Obes Res Clin Pract. 2020 Jan-Feb;14(1):34-38. doi: 10.1016/j.orcp.2019.10.003. Epub 2019 Nov 9.
• [2] Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of perilipin 5?.J Physiol. 2018 Mar 1;596(5):857-868. doi: 10.1113/JP275182. Epub 2017 Nov 23.
• [3] Perilipin 5 deficiency promotes atherosclerosis progression through accelerating inflammation, apoptosis, and oxidative stress.J Cell Biochem. 2019 Nov;120(11):19107-19123. doi: 10.1002/jcb.29238. Epub 2019 Jul 11.
• [4] Lipid storage droplet protein 5 reduces sodium palmitateinduced lipotoxicity in human normal liver cells by regulating lipid metabolismrelated factors.Mol Med Rep. 2019 Aug;20(2):879-886. doi: 10.3892/mmr.2019.10360. Epub 2019 Jun 6.
• [5] Plin5 deficiency exacerbates pressure overload-induced cardiac hypertrophy and heart failure by enhancing myocardial fatty acid oxidation and oxidative stress.Free Radic Biol Med. 2019 Sep;141:372-382. doi: 10.1016/j.freeradbiomed.2019.07.006. Epub 2019 Jul 7.
• [6] Perilipin 5 alleviates HCV NS5A-induced lipotoxic injuries in liver.Lipids Health Dis. 2019 Apr 6;18(1):87. doi: 10.1186/s12944-019-1022-7.
• [7] Perilipin 5 and Lipocalin 2 Expression in Hepatocellular Carcinoma.Cancers (Basel). 2019 Mar 19;11(3):385. doi: 10.3390/cancers11030385.
• [8] 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.
• [9] Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance.Physiol Behav. 2009 Mar 23;96(4-5):723-8. doi: 10.1016/j.physbeh.2009.01.011.
• [10] Polymorphisms in XPC gene and risk for prostate cancer.Mol Biol Rep. 2019 Feb;46(1):1117-1125. doi: 10.1007/s11033-018-4572-2. Epub 2018 Dec 14.
• [11] Perilipin 5 is protective in the ischemic heart.Int J Cardiol. 2016 Sep 15;219:446-54. doi: 10.1016/j.ijcard.2016.06.037. Epub 2016 Jun 16.
• [12] Widespread expression of perilipin 5 in normal human tissues and in diseases is restricted to distinct lipid droplet subpopulations.Cell Tissue Res. 2018 Oct;374(1):121-136. doi: 10.1007/s00441-018-2845-7. Epub 2018 May 11.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] 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.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 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.
• [17] 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.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [21] 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.
• [22] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [23] 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.
• [24] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.