Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLBLG11)

• DOT Name: F-box/WD repeat-containing protein 10 (FBXW10)
• Synonyms: F-box and WD-40 domain-containing protein 10; Ubiquitin ligase-specificity factor
• Gene Name: FBXW10
• Related Disease:
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: FBW10_HUMAN
• Pfam ID: PF00400
• Sequence:
  MENLESRLKNAPYFRCEKGTDSIPLCRKCETCVLAWKIFSTKEWFCRINDISQRRFLVGI
  LKQLNSLYLLHYFQNILQTTQGKDFIYNRSRINLSKKEGKVVKSSLNQMLDKTVEQKMKE
  ILYWFANSTQWTKANYTLLLLQMCNPKLLLTAANVIRVLFLREENNISGLNQDITDVCFS
  PEKDHSSKSATSQVYWTAKTQHTSLPLSKAPENEHLLGAASNPEEPWRNSLRCISEMNRL
  FSGKGDITKPGYDPCNLLVDLDDIRDLSSGFSKYRDFIRYLPIHLSKYILRMLDRHTLNK
  CASVSQHWAAMAQQVKMDLSAHGFIQNQITFLQGSYTRGIDPNYANKVSIPVPKMVDDGK
  SMRVKHPKWKLRTKNEYNLWTAYQNEETQQVLIEERNVFCGTYNVRILSDTWDQNRVIHY
  SGGDLIAVSSNRKIHLLDIIQVKAIPVEFRGHAGSVRALFLCEEENFLLSGSYDLSIRYW
  DLKSGVCTRIFGGHQGTITCMDLCKNRLVSGGRDCQVKVWDVDTGKCLKTFRHKDPILAT
  RINDTYIVSSCERGLVKVWHIAMAQLVKTLSGHEGAVKCLFFDQWHLLSGSTDGLVMAWS
  MVGKYERCLMAFKHPKEVLDVSLLFLRVISACADGKIRIYNFLNGNCMKVLKANGRGDPV
  LSFFIQGNRMVVNTESNVLMFQFEHIKWQYAVEKTKQKKNKEKEEEKEENSLMEILSKCN
  IQVHSPRESVSSKQTVIQELLPGKPPKSRVLLKPAKFSSAVLIEELQSQGKSKSPRRDAD
  DVEKAQKQGQLETPGKLPSHPKKKSWKIPMSPDQFLLTVSALQHAHNSGEFAYPCRPQTE
  ITDVWGPSISYPRKVLNFKGKSIQRAVDRLRLSNPPIDVKRTSIPLEIQKLQPNLKISLH
  SPRVQSTIPQPMIIRSRFSGSLKGGDQVTSSIERAVCSTGPLTSMQVIKPNRMLAPQVGT
  ATLSLKKERPRIYTALDPFRVNTEFVLLTVKEEKEHQEAKMKEYQARESTGVVDPGKVSK
  AAWIRKIKGLPIDNFTKQGKTAAPELGQNVFI
• Function: Probable substrate-recognition component of a SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Overexpression is leading to degradation of CBX5 and CBX1.
• Reactome Pathway:
  Neddylation (R-HSA-8951664)
  Antigen processing (R-HSA-983168)
  Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of F-box/WD repeat-containing protein 10 (FBXW10).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of F-box/WD repeat-containing protein 10 (FBXW10).	[3]

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 increases the methylation of F-box/WD repeat-containing protein 10 (FBXW10).	[4]

References

• [1] FBXW10 promotes hepatocarcinogenesis in male patients and mice.Carcinogenesis. 2020 Jul 10;41(5):689-698. doi: 10.1093/carcin/bgz138.
• [2] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [3] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [4] 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.