Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQT4M45)

• DOT Name: Ankyrin repeat and SOCS box protein 14 (ASB14)
• Synonyms: ASB-14
• Gene Name: ASB14
• Related Disease:
  Cardiac failure
  Congestive heart failure
• UniProt ID: ASB14_HUMAN
• Pfam ID: PF12796 ; PF07525
• Sequence:
  MDNYTSDEDIDEDFDTQLIIQQSLQDIYKPGTAQHAPKDESLHSFLSADYKKIVETIEKV
  GKEDALSHLTKYHSAFGEADEIGWIPLHKAAVQLNRKILEITLSASDPSLWEQTTHNGET
  PLFLAVSSCLLENATFLLLNGCNPNAKNFEGNSPLLAAVLRDCYDMAALLINYGADVNLR
  CANERTALHEAAKLGREDMVKLMLVSGAHPDPQSTYGFTPLALAAQSGHTEIMEMLLRKG
  KIFCLASDSSSILLEAASGGNPDAVALLLEYGADANIPKNSGHLPIHVAADRGHLLALKI
  LIPVTDLAAIKQSGISPVHCAAAGAHPQCLELLIQAGFDVNFMLDQRINKHYDDHRKSAL
  YFAVSNSDLSSVKLLLSAGALPNQDPVNCLQIALRMGNYELISLLLRHGANVNYFCRVNP
  LHFPSALQYTLKDEVMLRMLLNYGYDTERCFDCPHGDKVHPSYTVEGWTSTVIKDTKFCE
  VITLSWLQHLSGKVVRVMLDYVDQVRICSKLKAVLQKQGIWSEIHFILTNPRSLKHLCRL
  KIRKCMGRLHLRCPVFMSFLPLPNRLKAYVLYKEYDLYGQGIFTGTW
• Function: May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ankyrin repeat and SOCS box protein 14 (ASB14).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Ankyrin repeat and SOCS box protein 14 (ASB14).	[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 decreases the methylation of Ankyrin repeat and SOCS box protein 14 (ASB14).	[4]

References

• [1] Potential biomarkers for heart failure.J Cell Physiol. 2019 Jun;234(6):9467-9474. doi: 10.1002/jcp.27632. Epub 2018 Oct 28.
• [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] 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.