Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRHL1AP)

• DOT Name: Dynein assembly factor with WD repeat domains 1 (DAW1)
• Synonyms: Outer row dynein assembly protein 16 homolog; WD repeat-containing protein 69
• Gene Name: DAW1
• Related Disease: Allergic rhinitis
• UniProt ID: DAW1_HUMAN
• PDB ID: 5NNZ
• Pfam ID: PF00400
• Sequence:
  MKLKSLLLRYYPPGIMLEYEKHGELKTKSIDLLDLGPSTDVSALVEEIQKAEPLLTASRT
  EQVKLLIQRLQEKLGQNSNHTFYLFKVLKAHILPLTNVALNKSGSCFITGSYDRTCKLWD
  TASGEELNTLEGHRNVVYAIAFNNPYGDKIATGSFDKTCKLWSVETGKCYHTFRGHTAEI
  VCLSFNPQSTLVATGSMDTTAKLWDIQNGEEVYTLRGHSAEIISLSFNTSGDRIITGSFD
  HTVVVWDADTGRKVNILIGHCAEISSASFNWDCSLILTGSMDKTCKLWDATNGKCVATLT
  GHDDEILDSCFDYTGKLIATASADGTARIFSAATRKCIAKLEGHEGEISKISFNPQGNHL
  LTGSSDKTARIWDAQTGQCLQVLEGHTDEIFSCAFNYKGNIVITGSKDNTCRIWR
• Function: Required for axonemal dynein assembly and ciliary motility in ciliated organs, including Kupffer's vesicle, during embryogenesis. Facilitates the onset of robust cilia motility during development.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Allergic rhinitis	DIS3U9HN	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[5]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[6]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Dynein assembly factor with WD repeat domains 1 (DAW1).	[10]

2 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 Dynein assembly factor with WD repeat domains 1 (DAW1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Dynein assembly factor with WD repeat domains 1 (DAW1).	[9]

References

• [1] Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nat Genet. 2018 Aug;50(8):1072-1080. doi: 10.1038/s41588-018-0157-1. Epub 2018 Jul 16.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [8] 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.
• [9] 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.
• [10] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.