Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3NU4DH)

• DOT Name: Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4)
• Synonyms: AGAP-4; Centaurin-gamma-like family member 1; Centaurin-gamma-like family member 5
• Gene Name: AGAP4
• Related Disease: Hepatocellular carcinoma
• UniProt ID: AGAP4_HUMAN
• Pfam ID: PF12796 ; PF01412
• Sequence:
  MGNILTCRVHPSVSLEFDQQQGSVCPSESEIYEAGAGDRMAGAPMAAAVQPAEVTVEVGE
  DLHMHHVRDREMPEALEFNPSANPEASTIFQRNSQTDVVEIRRSNCTNHVSTVRFSQQYS
  LCSTIFLDDSTAIQHYLTMTIISVTLEIPHHITQRDADRSLSIPDEQLHSFAVSTVHIMK
  KRNGGGSLNNYSSSIPSTPSTSQEDPQFSVPPTANTPTPVCKRSMRWSNLFTSEKGSDPD
  KERKAPENHADTIGSGRAIPIKQGMLLKRSGKWLKTWKKKYVTLCSNGVLTYYSSLGDYM
  KNIHKKEIDLQTSTIKVPGKWPSLATSACTPISTSKSNGLSKDMDTGLGDSICFSPSISS
  TTSPKLNPPPSPHANKKKHLKKKSTNNFMIVSATGQTWHFEATTYEERDAWVQAIQSQIL
  ASLQSCESSKSKSQLTSQSKAMALQSIQNMRGNAHCVDCETQNPKWASLNLGVLMCIECS
  GIHRSLGTRLSRVRSLELDDWPVELRKVMSSIGNDLANSIWEGSSQGQTKPSEKSTREEK
  ERWIRSKYEEKLFLAPLPCTELSLGQQLLRATADEDLQTAILLLAHGSREEVNETCGEGD
  GCTALHLACRKGNVVLAQLLIWYGVDVMARDAHGNTALTYARQASSQECINVLLQYGCPD
  KCV
• Function: Putative GTPase-activating protein.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

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

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 Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[4]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 4 (AGAP4).	[8]

References

• [1] ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion.J Biol Chem. 2008 May 30;283(22):14915-26. doi: 10.1074/jbc.M709717200. Epub 2008 Apr 8.
• [2] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.