Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6LMZ17)

• DOT Name: Dynein axonemal intermediate chain 4 (DNAI4)
• Synonyms: WD repeat-containing protein 78
• Gene Name: DNAI4
• UniProt ID: DNAI4_HUMAN
• PDB ID: 8J07
• Pfam ID: PF00400
• Sequence:
  MTPGKHSGASARAANGGAWGYRDFRGGQKKGWCTTPQLVATMPVSPAGSHKQQNFGLNNA
  TQPKKSISFFATMKATSVKGYTGANQSRMAVSKTVLIPPELKTVEKPNPNIKTTQVFDIN
  GTDVTPRPLYHPDPLTGTAKPSKLLTSQEGSLGSEFISSYSLYQNTINPSTLGQFTRSVL
  GSSTVSKSSVSASESIAEDLEEPSYKRERLTSFTDLQVIRAAPEKIVTKEDLEKNIEIIL
  TETETLRFFDLPTVMVSVESEEAEKVTQRNKNYEVLCRNRLGNDLYVERMMQTFNGAPKN
  KDVQCDKIIMEDKGIMSTAWDLYDSYNAMELVSLSVKQSVVESSSKANVLPKDQDQRLPG
  STTEKNSETSSLMDIENVILAKIHEDEEDHSDAILKSDKFHQDLFFMERVLMENIFQPKL
  AAYRQLPVLKEPEPEEPEDVLESAKHEEVEEESKKEEEEEIHAEESTIPANLERLWSFSC
  DLTKGLNVSSLAWNKTNPDLLAVGYGHFGFKEQKRGLACCWSIKNPMWPERIYQSPYGVT
  AVDFSIGAPNLLAVGYHNGTIAIYNVRSNSNVPVLDSSESPQKHLGPVWQLQWIEQDRGT
  TGDGKREILVSISADGRISKWVIRKGLDCYDLMRLKRTTAASNKKGGEKEKKDEALISRQ
  APGMCFAFHPKDTNIYLAGTEEGHIHKCSCSYNEQYLDTYRGHKGPVYKVTWNPFCHDVF
  LSCSADWGVIIWQQENVKPSLSFYPATSVVYDVAWSPKSSYIFAAANENRVEIWDLHIST
  LDPLIVNTANPGIKFTTILFAKQTDCLLVGDSDGQVSVYELRNMPTVLETGRGDIMDTLL
  GSKSNQSA
• Function: Plays a critical role in the assembly of axonemal dynein complex, thereby playing a role in ciliary motility.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Dynein axonemal intermediate chain 4 (DNAI4).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Dynein axonemal intermediate chain 4 (DNAI4).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Dynein axonemal intermediate chain 4 (DNAI4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dynein axonemal intermediate chain 4 (DNAI4).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Dynein axonemal intermediate chain 4 (DNAI4).	[4]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Dynein axonemal intermediate chain 4 (DNAI4).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [4] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [5] 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.
• [6] 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.