Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFGCB9U)

• DOT Name: Plasmolipin (PLLP)
• Synonyms: Plasma membrane proteolipid
• Gene Name: PLLP
• Related Disease:
  Bardet biedl syndrome
  Bardet-Biedl syndrome 2
  Demyelinating polyneuropathy
  Malignant mesothelioma
  Schizophrenia
  Keratoconus
• UniProt ID: PLLP_HUMAN
• Pfam ID: PF01284
• Sequence:
  MAEFPSKVSTRTSSPAQGAEASVSALRPDLGFVRSRLGALMLLQLVLGLLVWALIADTPY
  HLYPAYGWVMFVAVFLWLVTIVLFNLYLFQLHMKLYMVPWPLVLMIFNISATVLYITAFI
  ACSAAVDLTSLRGTRPYNQRAAASFFACLVMIAYGVSAFFSYQAWRGVGSNAATSQMAGG
  YA
• Function: Appears to be involved in myelination. Could also participate in ion transport events as addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K(+)-selective.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bardet biedl syndrome	DISTBNZW	Strong	Genetic Variation	[1]
Bardet-Biedl syndrome 2	DIS1WLAX	Strong	Biomarker	[1]
Demyelinating polyneuropathy	DIS7IO4W	Strong	Biomarker	[1]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Keratoconus	DISOONXH	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Plasmolipin (PLLP) decreases the response to substance of Arsenic trioxide.	[25]

19 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 Plasmolipin (PLLP).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Plasmolipin (PLLP).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Plasmolipin (PLLP).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Plasmolipin (PLLP).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Plasmolipin (PLLP).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Plasmolipin (PLLP).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Plasmolipin (PLLP).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Plasmolipin (PLLP).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Plasmolipin (PLLP).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Plasmolipin (PLLP).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Plasmolipin (PLLP).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Plasmolipin (PLLP).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Plasmolipin (PLLP).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Plasmolipin (PLLP).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Plasmolipin (PLLP).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Plasmolipin (PLLP).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Plasmolipin (PLLP).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Plasmolipin (PLLP).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Plasmolipin (PLLP).	[24]

2 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 Plasmolipin (PLLP).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Plasmolipin (PLLP).	[19]

References

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• [2] MicroRNA and mRNA features of malignant pleural mesothelioma and benign asbestos-related pleural effusion.Biomed Res Int. 2015;2015:635748. doi: 10.1155/2015/635748. Epub 2015 Feb 1.
• [3] Microarray analysis of postmortem temporal cortex from patients with schizophrenia.J Neurosci Res. 2004 Sep 15;77(6):858-66. doi: 10.1002/jnr.20208.
• [4] RNA-Seq analysis and comparison of corneal epithelium in keratoconus and myopia patients.Sci Rep. 2018 Jan 10;8(1):389. doi: 10.1038/s41598-017-18480-x.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [15] 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.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [21] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [22] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [25] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.