Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG1A0QP)

• DOT Name: Dynein axonemal intermediate chain 3 (DNAI3)
• Synonyms: Testis development protein NYD-SP29; WD repeat-containing protein 63
• Gene Name: DNAI3
• UniProt ID: DNAI3_HUMAN
• PDB ID: 8J07
• Sequence:
  MAPKQKKKTSRGKKRLKPVLAASEDMEPVNMESMGHPEIYPLVLTTKTQEIFNCRIDEDV
  TDEQPYKLINKEDIFEDLRNRAAVSDFHPVKKIVQEYPGNELLLVYDKDFKYGLNFYLIA
  TEEGKENYLNPPEVPEEQEEYKEHIPEDVYIYKPPVSKPWVSLGSEKEIEEESVTESTKQ
  ITYMISRKRSEFGAPIKFSDQNASSVKDAYIECTAYPDKNFTLKQLEKDVGMQVIPQIKD
  ISTQTKWTYPKNATTQYYPREFSEEEKETLKQSKPLVDFLNNASISVEIALQQNEIMNTF
  IDDWKYLAEEEGTFGDKTDTHLKEYQSFTDLHSPTEKMITCVSWHPTIYGLIAVSVAVRL
  SFEDRVHFSGKLLLQPSLILFWSFSDPIHPQLMLESPDDIFCFKFCPSDPNIIAGGCING
  QIVMWDITAHADRIENIKAGGSRSKRATLKPMFLLEPESNKEAMYIRHCAVSSIENGHKK
  VITDIHWLSDTFEINRMGSVFENRSGICCQLVTCSADCTICFWDIRPQKPLTPQTTEKKK
  EESIEIPFDVPSTFLHLDLSWKPLTKVRLSKGETSLDHCPTKISLNEDHLLCKTQDKMLA
  QSKTEKAEEMNPYHNLESGMANLLKPIDDFCTKFFVGTEEGEVIYTDWKMEKDPETGRLM
  SKKPVSHHTIHDGTVHTIQRSPFYNDIILTVGGWNVAIWKEGVMTGPLLQSCCAPKRYTS
  GHWSLTRPGVFYIGREDGYIDIWDLLEKTHEPAQSQNICITMITYIKPWIFSSKQQFIAT
  ADYYGTLHILEIPWTLSRPSTNEMASVNHYFEREVKHLEYVEQRKKIREQEKKEMELEMA
  KKKVKTYQKSKEQMQAELKMDYESYLELEKTVLINLGLIKVTEKGSYMEVM
• Function: Acts as a negative regulator of cell migration, invasion, and metastasis downstream of p53/TP53, through inhibition of Arp2/3 complex-mediated actin polymerization. Via its association with the multisubunit axonemal dynein complex, is potentially involved in the regulation of cilia function. May play a role in osteogenesis of dental tissue-derived mesenchymal stem cells.
• KEGG Pathway: Motor proteins (hsa04814)

Molecular Interaction Atlas (MIA) of This DOT

11 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 Dynein axonemal intermediate chain 3 (DNAI3).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[3]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[4]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[5]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[5]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[6]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Dynein axonemal intermediate chain 3 (DNAI3).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [5] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [6] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.