Details of Drug Off-Target (DOT)

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

• DOT Name: Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1)
• Synonyms: Oligosaccharyl transferase subunit DAD1; Defender against cell death 1; DAD-1
• Gene Name: DAD1
• Related Disease:
  Advanced cancer
  Allergic asthma
  Asthma
  Barrett esophagus
  Familial multiple trichoepithelioma
  Carcinoid tumor
  Small-cell lung cancer
  Neuroendocrine neoplasm
• UniProt ID: DAD1_HUMAN
• PDB ID: 6S7O; 6S7T; 8B6L
• Pfam ID: PF02109
• Sequence:
  MSASVVSVISRFLEEYLSSTPQRLKLLDAYLLYILLTGALQFGYCLLVGTFPFNSFLSGF
  ISCVGSFILAVCLRIQINPQNKADFQGISPERAFADFLFASTILHLVVMNFVG
• Function: Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. Required for the assembly of both SST3A- and SS3B-containing OST complexes. Loss of the DAD1 protein triggers apoptosis.
• KEGG Pathway:
  N-Glycan biosynthesis (hsa00510)
  Various types of N-glycan biosynthesis (hsa00513)
  Metabolic pathways (hsa01100)
  Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Maturation of spike protein (R-HSA-9694548)
  Asparagine N-linked glycosylation (R-HSA-446203)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[2]
Asthma	DISW9QNS	Strong	Biomarker	[2]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[3]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Posttranslational Modification	[3]
Carcinoid tumor	DISMNRDC	moderate	Genetic Variation	[4]
Small-cell lung cancer	DISK3LZD	moderate	Biomarker	[5]
Neuroendocrine neoplasm	DISNPLOO	Limited	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1) increases the Apoptosis ADR of Paclitaxel.	[23]

18 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 Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[18]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[21]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 (DAD1).	[20]

References

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• [12] Apoptosis-related mRNA expression profiles of ovarian cancer cell lines following cisplatin treatment. J Gynecol Oncol. 2010 Dec 30;21(4):255-61. doi: 10.3802/jgo.2010.21.4.255. Epub 2010 Dec 31.
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• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [16] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
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• [18] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [19] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.