Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW0JG0U)

• DOT Name: Protein yippee-like 2
• Gene Name: YPEL2
• Related Disease: Retinitis pigmentosa
• UniProt ID: YPEL2_HUMAN
• Pfam ID: PF03226
• Sequence:
  MVKMTRSKTFQAYLPSCHRTYSCIHCRAHLANHDELISKSFQGSQGRAYLFNSVVNVGCG
  PAEERVLLTGLHAVADIYCENCKTTLGWKYEHAFESSQKYKEGKYIIELAHMIKDNGWD
• Tissue Specificity: Widely expressed. Detected in fetal and adult kidney, heart, liver, lung and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Retinitis pigmentosa	DISCGPY8	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein yippee-like 2.	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein yippee-like 2.	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein yippee-like 2.	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein yippee-like 2.	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein yippee-like 2.	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein yippee-like 2.	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein yippee-like 2.	[7]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Protein yippee-like 2.	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein yippee-like 2.	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein yippee-like 2.	[7]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Protein yippee-like 2.	[10]
GDC0941	DM1YAK6	Phase 2	GDC0941 increases the expression of Protein yippee-like 2.	[11]
GDC-0980/RG7422	DMF3MV1	Phase 2	GDC-0980/RG7422 increases the expression of Protein yippee-like 2.	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein yippee-like 2.	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein yippee-like 2.	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein yippee-like 2.	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Protein yippee-like 2.	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein yippee-like 2.	[17]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein yippee-like 2.	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein yippee-like 2.	[19]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Protein yippee-like 2.	[20]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of Protein yippee-like 2.	[21]

References

• [1] Structural Variants Create New Topological-Associated Domains and Ectopic Retinal Enhancer-Gene Contact in Dominant Retinitis Pigmentosa. Am J Hum Genet. 2020 Nov 5;107(5):802-814. doi: 10.1016/j.ajhg.2020.09.002. Epub 2020 Oct 5.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] 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.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [11] Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models. Clin Cancer Res. 2012 Dec 15;18(24):6771-83. doi: 10.1158/1078-0432.CCR-12-2347. Epub 2012 Nov 7.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] 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.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [21] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.