Details of Drug Off-Target (DOT)

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

• DOT Name: Nucleoporin p54 (NUP54)
• Synonyms: 54 kDa nucleoporin
• Gene Name: NUP54
• Related Disease:
  Chromosomal disorder
  Neoplasm
  Dystonia 37, early-onset, with striatal lesions
• UniProt ID: NUP54_HUMAN
• PDB ID: 4JNU; 4JNV; 4JO7; 4JO9; 5IJN; 5IJO; 7N8R; 7PER; 7R5J; 7R5K
• Pfam ID: PF13874 ; PF18437
• Sequence:
  MAFNFGAPSGTSGTAAATAAPAGGFGGFGTTSTTAGSAFSFSAPTNTGTTGLFGGTQNKG
  FGFGTGFGTTTGTSTGLGTGLGTGLGFGGFNTQQQQQTTLGGLFSQPTQAPTQSNQLINT
  ASALSAPTLLGDERDAILAKWNQLQAFWGTGKGYFNNNIPPVEFTQENPFCRFKAVGYSC
  MPSNKDEDGLVVLVFNKKETEIRSQQQQLVESLHKVLGGNQTLTVNVEGTKTLPDDQTEV
  VIYVVERSPNGTSRRVPATTLYAHFEQANIKTQLQQLGVTLSMTRTELSPAQIKQLLQNP
  PAGVDPIIWEQAKVDNPDSEKLIPVPMVGFKELLRRLKVQDQMTKQHQTRLDIISEDISE
  LQKNQTTSVAKIAQYKRKLMDLSHRTLQVLIKQEIQRKSGYAIQADEEQLRVQLDTIQGE
  LNAPTQFKGRLNELMSQIRMQNHFGAVRSEERYYIDADLLREIKQHLKQQQEGLSHLISI
  IKDDLEDIKLVEHGLNETIHIRGGVFS
• Function: Component of the nuclear pore complex, a complex required for the trafficking across the nuclear membrane.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  Transport of the SLBP independent Mature mRNA (R-HSA-159227)
  Transport of the SLBP Dependant Mature mRNA (R-HSA-159230)
  Transport of Mature mRNA Derived from an Intronless Transcript (R-HSA-159231)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)
  Rev-mediated nuclear export of HIV RNA (R-HSA-165054)
  Transport of Ribonucleoproteins into the Host Nucleus (R-HSA-168271)
  NS1 Mediated Effects on Host Pathways (R-HSA-168276)
  Viral Messenger RNA Synthesis (R-HSA-168325)
  NEP/NS2 Interacts with the Cellular Export Machinery (R-HSA-168333)
  Regulation of Glucokinase by Glucokinase Regulatory Protein (R-HSA-170822)
  Nuclear import of Rev protein (R-HSA-180746)
  Vpr-mediated nuclear import of PICs (R-HSA-180910)
  snRNP Assembly (R-HSA-191859)
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  SUMOylation of ubiquitinylation proteins (R-HSA-3232142)
  Nuclear Pore Complex (NPC) Disassembly (R-HSA-3301854)
  Regulation of HSF1-mediated heat shock response (R-HSA-3371453)
  SUMOylation of SUMOylation proteins (R-HSA-4085377)
  SUMOylation of chromatin organization proteins (R-HSA-4551638)
  SUMOylation of RNA binding proteins (R-HSA-4570464)
  SUMOylation of DNA replication proteins (R-HSA-4615885)
  Transcriptional regulation by small RNAs (R-HSA-5578749)
  Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) (R-HSA-5619107)
  tRNA processing in the nucleus (R-HSA-6784531)
  HCMV Early Events (R-HSA-9609690)
  HCMV Late Events (R-HSA-9610379)
  Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  ISG15 antiviral mechanism (R-HSA-1169408)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Dystonia 37, early-onset, with striatal lesions	DISM732R	Limited	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleoporin p54 (NUP54).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleoporin p54 (NUP54).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleoporin p54 (NUP54).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nucleoporin p54 (NUP54).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nucleoporin p54 (NUP54).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Nucleoporin p54 (NUP54).	[8]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Nucleoporin p54 (NUP54).	[9]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Nucleoporin p54 (NUP54).	[9]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Nucleoporin p54 (NUP54).	[9]

1 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 Nucleoporin p54 (NUP54).	[10]

References

• [1] Nucleoporin 54 contributes to homologous recombination repair and post-replicative DNA integrity.Nucleic Acids Res. 2018 Sep 6;46(15):7731-7746. doi: 10.1093/nar/gky569.
• [2] LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma.World J Gastroenterol. 2010 Apr 28;16(16):2046-54. doi: 10.3748/wjg.v16.i16.2046.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [10] 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.