Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7Z6F1F)

• DOT Name: Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6)
• Synonyms: AGAP-6; Centaurin-gamma-like family member 3
• Gene Name: AGAP6
• UniProt ID: AGAP6_HUMAN
• Pfam ID: PF12796 ; PF01412
• Sequence:
  MGNILTCRVHPSVSLEFDQQQGSVCPSESETYEAGARDRMAGAPMAAAVQPAEVTVEVGE
  DLHMHHVRDREMPEALEFNPSANPEASTIFQRNSQTDVVEIRRSNCTNHVSAVRFSQQYS
  LCSTIFLDDSTAIQHYLTMTIISVTLEIPHHITQRDADRTLSIPDEQLHSFAVSTVHIMK
  KRNGGGSLNNYSSSIPSTPSTSQEDPQFSVPPTANTPTPVCKRSMRWSNLFTSEKGSDPD
  KERKAPENHADTIGSGRAIPIKQGMLLKRSGKWLKTWKKKYVTLCSNGMLTYYSSLGDYM
  KNIHKKEIDLQTSTIKVPGKWPSLATSACTPISSSKSNGLSKDMDTGLGDSICFSPSISS
  TTSPKLNPPPSPHANKKKHLKKKSTNNFMIVSATGQTWHFEATTYEERDAWVQAIQSQIL
  ASLQSCESSKSKSQLTSQSEAMALQSIQNMRGNAHCVDCETQNPKWASLNLGVLMCIECS
  GIHRSLGPHLSRVRSLELDDWPVELRKVMSSIVNDLANSIWEGSSQGQTKPSEKSTREEK
  ERWIRSKYEEKLFLAPLPCTELSLGQQLLRATADEDLQTAILLLAHGSCEEVNETCGEGD
  GCTALHLACRKGNVVLAQLLIWYGVDVMARDAHGNTALTYARQASSQECINVLLQYGCPD
  ECV
• Function: Putative GTPase-activating protein.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

5 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 Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 6 (AGAP6).	[5]

References

• [1] 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.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [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.