Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWNQ74H)

• DOT Name: Dihydropyrimidinase-related protein 2 (DPYSL2)
• Synonyms: DRP-2; Collapsin response mediator protein 2; CRMP-2; N2A3; Unc-33-like phosphoprotein 2; ULIP-2
• Gene Name: DPYSL2
• Related Disease: Schizophrenia
• UniProt ID: DPYL2_HUMAN
• PDB ID: 2GSE; 2VM8; 5LXX; 5MKV; 5MLE; 5X1A; 5X1C; 5X1D; 5YZ5; 5YZA; 5YZB; 6JV9; 6JVB; 7X68; 8DNM
• Pfam ID: PF01979
• Sequence:
  MSYQGKKNIPRITSDRLLIKGGKIVNDDQSFYADIYMEDGLIKQIGENLIVPGGVKTIEA
  HSRMVIPGGIDVHTRFQMPDQGMTSADDFFQGTKAALAGGTTMIIDHVVPEPGTSLLAAF
  DQWREWADSKSCCDYSLHVDISEWHKGIQEEMEALVKDHGVNSFLVYMAFKDRFQLTDCQ
  IYEVLSVIRDIGAIAQVHAENGDIIAEEQQRILDLGITGPEGHVLSRPEEVEAEAVNRAI
  TIANQTNCPLYITKVMSKSSAEVIAQARKKGTVVYGEPITASLGTDGSHYWSKNWAKAAA
  FVTSPPLSPDPTTPDFLNSLLSCGDLQVTGSAHCTFNTAQKAVGKDNFTLIPEGTNGTEE
  RMSVIWDKAVVTGKMDENQFVAVTSTNAAKVFNLYPRKGRIAVGSDADLVIWDPDSVKTI
  SAKTHNSSLEYNIFEGMECRGSPLVVISQGKIVLEDGTLHVTEGSGRYIPRKPFPDFVYK
  RIKARSRLAELRGVPRGLYDGPVCEVSVTPKTVTPASSAKTSPAKQQAPPVRNLHQSGFS
  LSGAQIDDNIPRRTTQRIVAPPGGRANITSLG
• Function: Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. May play a role in endocytosis.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Axon guidance (hsa04360)
• Reactome Pathway:
  Recycling pathway of L1 (R-HSA-437239)
  CRMPs in Sema3A signaling (R-HSA-399956)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	No Known	Unknown	[1]

5 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 Dihydropyrimidinase-related protein 2 (DPYSL2).	[2]
G1	DMTV42K	Phase 1/2	G1 increases the phosphorylation of Dihydropyrimidinase-related protein 2 (DPYSL2).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Dihydropyrimidinase-related protein 2 (DPYSL2).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dihydropyrimidinase-related protein 2 (DPYSL2).	[23]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Dihydropyrimidinase-related protein 2 (DPYSL2).	[22]

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 Dihydropyrimidinase-related protein 2 (DPYSL2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[12]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[14]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[15]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[16]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Dihydropyrimidinase-related protein 2 (DPYSL2).	[25]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Dihydropyrimidinase-related protein 2 (DPYSL2).	[17]
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Dihydropyrimidinase-related protein 2 (DPYSL2).	[19]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal affects the binding of Dihydropyrimidinase-related protein 2 (DPYSL2).	[26]

References

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• [14] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
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• [20] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [21] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [22] 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.
• [23] 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.
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