Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFE3RCV)

• DOT Name: Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1)
• Synonyms: EC 3.1.4.2; Glycerophosphodiester phosphodiesterase 5
• Gene Name: GPCPD1
• Related Disease:
  Eating disorder
  Endometrial carcinoma
  Obesity
• UniProt ID: GPCP1_HUMAN
• PDB ID: 2Z0B
• EC Number: 3.1.4.2
• Pfam ID: PF00686 ; PF03009
• Sequence:
  MTPSQVAFEIRGTLLPGEVFAICGSCDALGNWNPQNAVALLPENDTGESMLWKATIVLSR
  GVSVQYRYFKGYFLEPKTIGGPCQVIVHKWETHLQPRSITPLESEIIIDDGQFGIHNGVE
  TLDSGWLTCQTEIRLRLHYSEKPPVSITKKKLKKSRFRVKLTLEGLEEDDDDRVSPTVLH
  KMSNSLEISLISDNEFKCRHSQPECGYGLQPDRWTEYSIQTMEPDNLELIFDFFEEDLSE
  HVVQGDALPGHVGTACLLSSTIAESGKSAGILTLPIMSRNSRKTIGKVRVDYIIIKPLPG
  YSCDMKSSFSKYWKPRIPLDVGHRGAGNSTTTAQLAKVQENTIASLRNAASHGAAFVEFD
  VHLSKDFVPVVYHDLTCCLTMKKKFDADPVELFEIPVKELTFDQLQLLKLTHVTALKSKD
  RKESVVQEENSFSENQPFPSLKMVLESLPEDVGFNIEIKWICQQRDGMWDGNLSTYFDMN
  LFLDIILKTVLENSGKRRIVFSSFDADICTMVRQKQNKYPILFLTQGKSEIYPELMDLRS
  RTTPIAMSFAQFENLLGINVHTEDLLRNPSYIQEAKAKGLVIFCWGDDTNDPENRRKLKE
  LGVNGLIYDRIYDWMPEQPNIFQVEQLERLKQELPELKSCLCPTVSRFVPSSLCGESDIH
  VDANGIDNVENA
• Function: May be involved in the negative regulation of skeletal muscle differentiation, independently of its glycerophosphocholine phosphodiesterase activity.
• Tissue Specificity: Widely expressed, with highest expression in spinal chord.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Hydrolysis of LPE (R-HSA-1483152)
  Hydrolysis of LPC (R-HSA-1483115)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Eating disorder	DISVGXN0	Strong	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[19]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Glycerophosphocholine phosphodiesterase GPCPD1 (GPCPD1).	[10]

References

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• [2] Choline-releasing glycerophosphodiesterase EDI3 drives tumor cell migration and metastasis.Proc Natl Acad Sci U S A. 2012 May 22;109(21):8155-60. doi: 10.1073/pnas.1117654109. Epub 2012 May 8.
• [3] 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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• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] 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.
• [12] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [18] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.