Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOB42TH)

• DOT Name: Activating transcription factor 7-interacting protein 2 (ATF7IP2)
• Synonyms: ATF7-interacting protein 2; MBD1-containing chromatin-associated factor 2
• Gene Name: ATF7IP2
• UniProt ID: MCAF2_HUMAN
• Pfam ID: PF16788 ; PF16794
• Sequence:
  MASPDRSKRKILKAKKTMPLSCRKQVEMLNKSRNVEALKTAIGSNVPSGNQSFSPSVITR
  TTEITKCSPSENGASSLDSNKNSISEKSKVFSQNCIKPVEEIVHSETKLEQVVCSYQKPS
  RTTESPSRVFTEEAKDSLNTSENDSEHQTNVTRSLFEHEGACSLKSSCCPPSVLSGVVQM
  PESTVTSTVGDKKTDQMVFHLETNSNSESHDKRQSDNILCSEDSGFVPVEKTPNLVNSVT
  SNNCADDILKTDECSRTSISNCESADSTWQSSLDTNNNSHYQKKRMFSENEENVKRMKTS
  EQINENICVSLERQTAFLEQVRHLIQQEIYSINYELFDKKLKELNQRIGKTECRNKHEGI
  ADKLLAKIAKLQRRIKTVLLFQRNCLKPNMLSSNGASKVANSEAMILDKNLESVNSPIEK
  SSVNYEPSNPSEKGSKKINLSSDQNKSVSESNNDDVMLISVESPNLTTPITSNPTDTRKI
  TSGNSSNSPNAEVMAVQKKLDSIIDLTKEGLSNCNTESPVSPLESHSKAASNSKETTPLA
  QNAVQVPESFEHLPPLPEPPAPLPELVDKTRDTLPPQKPELKVKRVFRPNGIALTWNITK
  INPKCAPVESYHLFLCHENSNNKLIWKKIGEIKALPLPMACTLSQFLASNRYYFTVQSKD
  IFGRYGPFCDIKSIPGFSENLT
• Function: Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context. Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing SETDB1. The complex formed with MBD1 and SETDB1 represses transcription and probably couples DNA methylation and histone H3 'Lys-9' trimethylation (H3K9me3) activity (Probable).

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[1]

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 affects the methylation of Activating transcription factor 7-interacting protein 2 (ATF7IP2).	[6]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [8] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.