Details of Drug Off-Target (DOT)

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

• DOT Name: Axin interactor, dorsalization-associated protein (AIDA)
• Synonyms: Axin interaction partner and dorsalization antagonist
• Gene Name: AIDA
• Related Disease:
  Myocardial infarction
  Obesity
  Promyelocytic leukaemia
  Pneumonia
  Coronary atherosclerosis
  Coronary heart disease
• UniProt ID: AIDA_HUMAN
• Pfam ID: PF14186 ; PF08910
• Sequence:
  MSEVTRSLLQRWGASFRRGADFDSWGQLVEAIDEYQILARHLQKEAQAQHNNSEFTEEQK
  KTIGKIATCLELRSAALQSTQSQEEFKLEDLKKLEPILKNILTYNKEFPFDVQPVPLRRI
  LAPGEEENLEFEEDEEEGGAGAGSPDSFPARVPGTLLPRLPSEPGMTLLTIRIEKIGLKD
  AGQCIDPYITVSVKDLNGIDLTPVQDTPVASRKEDTYVHFNVDIELQKHVEKLTKGAAIF
  FEFKHYKPKKRFTSTKCFAFMEMDEIKPGPIVIELYKKPTDFKRKKLQLLTKKPLYLHLH
  QTLHKE
• Function: Acts as a ventralizing factor during embryogenesis. Inhibits axin-mediated JNK activation by binding axin and disrupting axin homodimerization. This in turn antagonizes a Wnt/beta-catenin-independent dorsalization pathway activated by AXIN/JNK-signaling.
• Tissue Specificity: Widely expressed in adult tissues, with highest expression in the heart and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Biomarker	[2]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[3]
Pneumonia	DIS8EF3M	Disputed	Biomarker	[4]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[5]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Axin interactor, dorsalization-associated protein (AIDA).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Axin interactor, dorsalization-associated protein (AIDA).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Axin interactor, dorsalization-associated protein (AIDA).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Axin interactor, dorsalization-associated protein (AIDA).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Axin interactor, dorsalization-associated protein (AIDA).	[10]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Axin interactor, dorsalization-associated protein (AIDA).	[11]

References

• [1] Cardiac Magnetic Resonance Myocardial Feature Tracking for Optimized Prediction of Cardiovascular Events Following Myocardial Infarction.JACC Cardiovasc Imaging. 2018 Oct;11(10):1433-1444. doi: 10.1016/j.jcmg.2017.11.034. Epub 2018 Feb 14.
• [2] AIDA Selectively Mediates Downregulation of Fat Synthesis Enzymes by ERAD to Retard Intestinal Fat Absorption and Prevent Obesity.Cell Metab. 2018 Apr 3;27(4):843-853.e6. doi: 10.1016/j.cmet.2018.02.021.
• [3] AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance.Blood. 2011 May 5;117(18):4716-25. doi: 10.1182/blood-2010-08-302950. Epub 2011 Mar 8.
• [4] Relationship Between the Quorum Network (Sensing/Quenching) and Clinical Features of Pneumonia and Bacteraemia Caused by A. baumannii.Front Microbiol. 2018 Dec 17;9:3105. doi: 10.3389/fmicb.2018.03105. eCollection 2018.
• [5] Integrative analysis of vascular endothelial cell genomic features identifies AIDA as a coronary artery disease candidate gene.Genome Biol. 2019 Jul 8;20(1):133. doi: 10.1186/s13059-019-1749-5.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [11] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.