Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT42BLWH)

• DOT Name: WW domain-binding protein 4
• Synonyms: WBP-4; Formin-binding protein 21; WW domain-containing-binding protein 4
• Gene Name: WBP4
• UniProt ID: WBP4_HUMAN
• PDB ID: 2DK1; 2JXW; 5O9Z; 6AHD; 7OS1
• Pfam ID: PF00397 ; PF06220
• Sequence:
  MADYWKSQPKKFCDYCKCWIADNRPSVEFHERGKNHKENVAKRISEIKQKSLDKAKEEEK
  ASKEFAAMEAAALKAYQEDLKRLGLESEILEPSITPVTSTIPPTSTSNQQKEKKEKKKRK
  KDPSKGRWVEGITSEGYHYYYDLISGASQWEKPEGFQGDLKKTAVKTVWVEGLSEDGFTY
  YYNTETGESRWEKPDDFIPHTSDLPSSKVNENSLGTLDESKSSDSHSDSDGEQEAEEGGV
  STETEKPKIKFKEKNKNSDGGSDPETQKEKSIQKQNSLGSNEEKSKTLKKSNPYGEWQEI
  KQEVESHEEVDLELPSTENEYVSTSEADGGGEPKVVFKEKTVTSLGVMADGVAPVFKKRR
  TENGKSRNLRQRGDDQ
• Function: Involved in pre-mRNA splicing as a component of the spliceosome. May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of WW domain-binding protein 4.	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of WW domain-binding protein 4.	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of WW domain-binding protein 4.	[3]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of WW domain-binding protein 4.	[4]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of WW domain-binding protein 4.	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of WW domain-binding protein 4.	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of WW domain-binding protein 4.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of WW domain-binding protein 4.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Borrelidin	DMBSQTR	Investigative	Borrelidin affects the binding of WW domain-binding protein 4.	[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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [5] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [6] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [7] 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.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Borrelidin modulates the alternative splicing of VEGF in favour of anti-angiogenic isoforms. Chem Sci. 2011 Feb 1;2011(2):273-278. doi: 10.1039/C0SC00297F.