Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVL01TR)

• DOT Name: Phospholipid phosphatase-related protein type 5 (PLPPR5)
• Synonyms: Lipid phosphate phosphatase-related protein type 5; Phosphatidic acid phosphatase type 2d; Plasticity-related gene 5 protein; PRG-5
• Gene Name: PLPPR5
• Related Disease:
  Breast cancer
  Breast carcinoma
  Cervical carcinoma
• UniProt ID: PLPR5_HUMAN
• Pfam ID: PF01569
• Sequence:
  MPLLPAALTSSMLYFQMVIMAGTVMLAYYFEYTDTFTVNVQGFFCHDSAYRKPYPGPEDS
  SAVPPVLLYSLAAGVPVLVIIVGETAVFCLQLATRDFENQEKTILTGDCCYINPLVRRTV
  RFLGIYTFGLFATDIFVNAGQVVTGNLAPHFLALCKPNYTALGCQQYTQFISGEEACTGN
  PDLIMRARKTFPSKEAALSVYAAMYLTMYITNTIKAKGTRLAKPVLCLGLMCLAFLTGLN
  RVAEYRNHWSDVIAGFLVGISIAVFLVVCVVNNFKGRQAENEHIHMDNLAQMPMISIPRV
  ESPLEKVTSVQNHITAFAEVT
• Function: Induces filopodia formation and promotes neurite growth in a CDC42-independent manner; impedes neurite growth inhibitory-mediated axonal retraction.
• Tissue Specificity: Isoform 1 is expressed in brain, lung, kidney and colon. Isoform 2 is expressed in placenta, skeletal muscle and kidney.
• Reactome Pathway: Lysosphingolipid and LPA receptors (R-HSA-419408)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Phospholipid phosphatase-related protein type 5 (PLPPR5).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phospholipid phosphatase-related protein type 5 (PLPPR5).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Phospholipid phosphatase-related protein type 5 (PLPPR5).	[5]

3 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 Phospholipid phosphatase-related protein type 5 (PLPPR5).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Phospholipid phosphatase-related protein type 5 (PLPPR5).	[7]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Phospholipid phosphatase-related protein type 5 (PLPPR5).	[8]

References

• [1] Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions.J Cell Biochem. 1995 Apr;57(4):680-90. doi: 10.1002/jcb.240570413.
• [2] New approach to human high-risk papillomavirus (HR-HPV) genotyping.Neoplasma. 2002;49(4):217-24.
• [3] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.