Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS42VUL)

• DOT Name: Speckle-type POZ protein-like (SPOPL)
• Synonyms: HIB homolog 2; Roadkill homolog 2
• Gene Name: SPOPL
• Related Disease: Medulloblastoma
• UniProt ID: SPOPL_HUMAN
• Pfam ID: PF00651 ; PF00917
• Sequence:
  MSREPTPPLPGDMSTGPIAESWCYTQVKVVKFSYMWTINNFSFCREEMGEVLKSSTFSSG
  PSDKMKWCLRVNPKGLDDESKDYLSLYLLLVSCPKSEVRAKFKFSLLNAKREETKAMESQ
  RAYRFVQGKDWGFKKFIRRDFLLDEANGLLPDDKLTLFCEVSVVQDSVNISGHTNTNTLK
  VPECRLAEDLGNLWENTRFTDCSFFVRGQEFKAHKSVLAARSPVFNAMFEHEMEESKKNR
  VEINDLDPEVFKEMMRFIYTGRAPNLDKMADNLLAAADKYALERLKVMCEEALCSNLSVE
  NVADTLVLADLHSAEQLKAQAIDFINRCSVLRQLGCKDGKNWNSNQATDIMETSGWKSMI
  QSHPHLVAEAFRALASAQCPQFGIPRKRLKQS
• Function: Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, but with relatively low efficiency. Cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL are less efficient than ubiquitin ligase complexes containing only SPOP. May function to down-regulate the activity of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain SPOP.
• KEGG Pathway: Hedgehog sig.ling pathway (hsa04340)
• Reactome Pathway: Hedgehog 'on' state (R-HSA-5632684)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Speckle-type POZ protein-like (SPOPL).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Speckle-type POZ protein-like (SPOPL).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Speckle-type POZ protein-like (SPOPL).	[4]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Speckle-type POZ protein-like (SPOPL).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Speckle-type POZ protein-like (SPOPL).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Speckle-type POZ protein-like (SPOPL).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Speckle-type POZ protein-like (SPOPL).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Speckle-type POZ protein-like (SPOPL).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Speckle-type POZ protein-like (SPOPL).	[8]

References

• [1] Expression and clinical relevance of SPOPL in medulloblastoma.Oncol Lett. 2017 Sep;14(3):3051-3056. doi: 10.3892/ol.2017.6500. Epub 2017 Jun 30.
• [2] 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.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.