Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTB3L8N)

• DOT Name: Axonemal dynein light intermediate polypeptide 1 (DNALI1)
• Synonyms: Inner dynein arm light chain, axonemal; hp28
• Gene Name: DNALI1
• Related Disease:
  B-cell neoplasm
  Neoplasm
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Autoimmune disease
  Brain neoplasm
  Bruton-type agammaglobulinemia
  Carcinoma of esophagus
  Encephalitis
  Glioma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Multiple sclerosis
  Myocardial infarction
  Myopia
  Schizophrenia
  Breast cancer
  Breast carcinoma
  Influenza
  Melanoma
  Nervous system inflammation
  Spermatogenic failure 83
• UniProt ID: IDLC_HUMAN
• PDB ID: 8J07
• Pfam ID: PF10211
• Sequence:
  MIPPADSLLKYDTPVLVSRNTEKRSPKARLLKVSPQQPGPSGSAPQPPKTKLPSTPCVPD
  PTKQAEEILNAILPPREWVEDTQLWIQQVSSTPSTRMDVVHLQEQLDLKLQQRQARETGI
  CPVRRELYSQCFDELIREVTINCAERGLLLLRVRDEIRMTIAAYQTLYESSVAFGMRKAL
  QAEQGKSDMERKIAELETEKRDLERQVNEQKAKCEATEKRESERRQVEEKKHNEEIQFLK
  RTNQQLKAQLEGIIAPKK
• Function: Involved in sperm flagellum assembly.
• Tissue Specificity: Expressed in many tissues. A smaller 0.9 kb and a larger 2.5 kb transcripts were detected at the highest level in the testis, at medium levels in the prostate, heart, liver, lung and pancreas, at low levels in the ovary, skeletal muscle and small intestine. Not detected in spleen, colon epithelium, thymus or peripheral blood leukocytes. The 0.9 kb transcript is expressed at a 20-fold higher level than the 2.5 kb transcript in the testis. Expressed in spermatozoa and airway epithelial cells (at protein level) .
• KEGG Pathway:
  Motor proteins (hsa04814)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Pathways of neurodegeneration - multiple diseases (hsa05022)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[5]
Bruton-type agammaglobulinemia	DISQ5ZYP	Strong	Biomarker	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[7]
Encephalitis	DISLD1RL	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[4]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[12]
Myopia	DISK5S60	Strong	Biomarker	[13]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[14]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[15]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[15]
Influenza	DIS3PNU3	moderate	Altered Expression	[16]
Melanoma	DIS1RRCY	moderate	Altered Expression	[15]
Nervous system inflammation	DISB3X5A	Limited	Altered Expression	[17]
Spermatogenic failure 83	DISGFKIT	Limited	Unknown	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[27]

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 Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Axonemal dynein light intermediate polypeptide 1 (DNALI1).	[26]

References

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• [8] Dysregulation of sonic hedgehog pathway and pericytes in the brain after lentiviral infection.J Neuroinflammation. 2019 Apr 13;16(1):86. doi: 10.1186/s12974-019-1463-y.
• [9] Antibodies to peptides detect new hepatitis B antigen: serological correlation with hepatocellular carcinoma.Science. 1985 Jan 25;227(4685):429-33. doi: 10.1126/science.2981434.
• [10] Interleukin 27 polymorphisms in HCV RNA positive patients: is there an impact on response to interferon therapy?.BMC Infect Dis. 2014;14 Suppl 5(Suppl 5):S5. doi: 10.1186/1471-2334-14-S5-S5. Epub 2014 Sep 5.
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• [12] Profiling analysis of long non-coding RNAs in early postnatal mouse hearts.Sci Rep. 2017 Mar 7;7:43485. doi: 10.1038/srep43485.
• [13] Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice.Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4362-70. doi: 10.1167/iovs.09-3998. Epub 2010 May 19.
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• [16] Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity.Front Microbiol. 2019 Mar 6;10:432. doi: 10.3389/fmicb.2019.00432. eCollection 2019.
• [17] IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells.J Immunol. 2009 May 1;182(9):5748-56. doi: 10.4049/jimmunol.0801162.
• [18] ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6. Am J Hum Genet. 2013 Aug 8;93(2):336-45. doi: 10.1016/j.ajhg.2013.06.007. Epub 2013 Jul 25.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [21] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [22] 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.
• [23] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [24] 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.
• [25] 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.
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