Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJDIQ3C)

• DOT Name: Dihydropyrimidinase-related protein 1 (CRMP1)
• Synonyms: DRP-1; Collapsin response mediator protein 1; CRMP-1; Inactive dihydropyrimidinase; Unc-33-like phosphoprotein 3; ULIP-3
• Gene Name: CRMP1
• UniProt ID: DPYL1_HUMAN
• PDB ID: 4B3Z
• Pfam ID: PF01979
• Sequence:
  MSYQGKKSIPHITSDRLLIKGGRIINDDQSLYADVYLEDGLIKQIGENLIVPGGVKTIEA
  NGRMVIPGGIDVNTYLQKPSQGMTAADDFFQGTRAALVGGTTMIIDHVVPEPGSSLLTSF
  EKWHEAADTKSCCDYSLHVDITSWYDGVREELEVLVQDKGVNSFQVYMAYKDVYQMSDSQ
  LYEAFTFLKGLGAVILVHAENGDLIAQEQKRILEMGITGPEGHALSRPEELEAEAVFRAI
  TIAGRINCPVYITKVMSKSAADIIALARKKGPLVFGEPIAASLGTDGTHYWSKNWAKAAA
  FVTSPPLSPDPTTPDYLTSLLACGDLQVTGSGHCPYSTAQKAVGKDNFTLIPEGVNGIEE
  RMTVVWDKAVATGKMDENQFVAVTSTNAAKIFNLYPRKGRIAVGSDADVVIWDPDKLKTI
  TAKSHKSAVEYNIFEGMECHGSPLVVISQGKIVFEDGNINVNKGMGRFIPRKAFPEHLYQ
  RVKIRNKVFGLQGVSRGMYDGPVYEVPATPKYATPAPSAKSSPSKHQPPPIRNLHQSNFS
  LSGAQIDDNNPRRTGHRIVAPPGGRSNITSLG
• Function: Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance. During the axon guidance process, acts downstream of SEMA3A to promote FLNA dissociation from F-actin which results in the rearrangement of the actin cytoskeleton and the collapse of the growth cone. Involved in invasive growth and cell migration. May participate in cytokinesis.
• Tissue Specificity: Brain.
• Reactome Pathway: CRMPs in Sema3A signaling (R-HSA-399956)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Dihydropyrimidinase-related protein 1 (CRMP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Dihydropyrimidinase-related protein 1 (CRMP1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dihydropyrimidinase-related protein 1 (CRMP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dihydropyrimidinase-related protein 1 (CRMP1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Dihydropyrimidinase-related protein 1 (CRMP1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dihydropyrimidinase-related protein 1 (CRMP1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the phosphorylation of Dihydropyrimidinase-related protein 1 (CRMP1).	[4]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of Dihydropyrimidinase-related protein 1 (CRMP1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Dihydropyrimidinase-related protein 1 (CRMP1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Dihydropyrimidinase-related protein 1 (CRMP1).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] 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.
• [9] 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.