Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHYEB4W)

• DOT Name: Phospholipase B-like 1 (PLBD1)
• Synonyms: EC 3.1.1.-; LAMA-like protein 1; Lamina ancestor homolog 1; Phospholipase B domain-containing protein 1
• Gene Name: PLBD1
• Related Disease: Non-small-cell lung cancer
• UniProt ID: PLBL1_HUMAN
• EC Number: 3.1.1.-
• Pfam ID: PF04916
• Sequence:
  MTRGGPGGRPGLPQPPPLLLLLLLLPLLLVTAEPPKPAGVYYATAYWMPAEKTVQVKNVM
  DKNGDAYGFYNNSVKTTGWGILEIRAGYGSQTLSNEIIMFVAGFLEGYLTAPHMNDHYTN
  LYPQLITKPSIMDKVQDFMEKQDKWTRKNIKEYKTDSFWRHTGYVMAQIDGLYVGAKKRA
  ILEGTKPMTLFQIQFLNSVGDLLDLIPSLSPTKNGSLKVFKRWDMGHCSALIKVLPGFEN
  ILFAHSSWYTYAAMLRIYKHWDFNVIDKDTSSSRLSFSSYPGFLESLDDFYILSSGLILL
  QTTNSVFNKTLLKQVIPETLLSWQRVRVANMMADSGKRWADIFSKYNSGTYNNQYMVLDL
  KKVKLNHSLDKGTLYIVEQIPTYVEYSEQTDVLRKGYWPSYNVPFHEKIYNWSGYPLLVQ
  KLGLDYSYDLAPRAKIFRRDQGKVTDTASMKYIMRYNNYKKDPYSRGDPCNTICCREDLN
  SPNPSPGGCYDTKVADIYLASQYTSYAISGPTVQGGLPVFRWDRFNKTLHQGMPEVYNFD
  FITMKPILKLDIK
• Function: In view of the small size of the putative binding pocket, it has been proposed that it may act as an amidase or a peptidase. Exhibits a weak phospholipase activity, acting on various phospholipids, including phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and lysophospholipids.
• Tissue Specificity: Expressed in neutrophils and monocytes.
• Reactome Pathway:
  Acyl chain remodelling of PE (R-HSA-1482839)
  Acyl chain remodelling of PI (R-HSA-1482922)
  Hydrolysis of LPC (R-HSA-1483115)
  Acyl chain remodelling of PC (R-HSA-1482788)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	Phospholipase B-like 1 (PLBD1) affects the response to substance of Gefitinib.	[1]

12 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 Phospholipase B-like 1 (PLBD1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phospholipase B-like 1 (PLBD1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Phospholipase B-like 1 (PLBD1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phospholipase B-like 1 (PLBD1).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Phospholipase B-like 1 (PLBD1).	[6]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Phospholipase B-like 1 (PLBD1).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Phospholipase B-like 1 (PLBD1).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phospholipase B-like 1 (PLBD1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Phospholipase B-like 1 (PLBD1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phospholipase B-like 1 (PLBD1).	[11]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Phospholipase B-like 1 (PLBD1).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Phospholipase B-like 1 (PLBD1).	[12]

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 affects the methylation of Phospholipase B-like 1 (PLBD1).	[9]

References

• [1] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [9] 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.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.