Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTADT64E)

• DOT Name: Nucleoporin NUP42 (NUP42)
• Synonyms: NLP-1; NUP42 homolog; Nucleoporin hCG1; Nucleoporin-42; Nucleoporin-like protein 2
• Gene Name: NUP42
• Related Disease:
  Autosomal dominant nonsyndromic hearing loss 5
  Hemochromatosis
  Chronic obstructive pulmonary disease
  Stroke
  Type-1/2 diabetes
  Peroxisome biogenesis disorder
  Chronic renal failure
  End-stage renal disease
• UniProt ID: NUP42_HUMAN
• PDB ID: 6B4F; 6B4I; 6B4J
• Pfam ID: PF18044
• Sequence:
  MAICQFFLQGRCRFGDRCWNEHPGARGAGGGRQQPQQQPSGNNRRGWNTTSQRYSNVIQP
  SSFSKSTPWGGSRDQEKPYFSSFDSGASTNRKEGFGLSENPFASLSPDEQKDEKKLLEGI
  VKDMEVWESSGQWMFSVYSPVKKKPNISGFTDISPEELRLEYHNFLTSNNLQSYLNSVQR
  LINQWRNRVNELKSLNISTKVALLSDVKDGVNQAAPAFGFGSSQAATFMSPGFPVNNSSS
  DNAQNFSFKTNSGFAAASSGSPAGFGSSPAFGAAASTSSGISTSAPAFGFGKPEVTSAAS
  FSFKSPAASSFGSPGFSGLPASLATGPVRAPVAPAFGGGSSVAGFGSPGSHSHTAFSKPS
  SDTFGNSSISTSLSASSSIIATDNVLFTPRDKLTVEELEQFQSKKFTLGKIPLKPPPLEL
  LNV
• Function: Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm; (Microbial infection) In case of infection by HIV-1, it may participate in the docking of viral Vpr at the nuclear envelope.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway: Nucleocytoplasmic transport (hsa03013)
• 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)
  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

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant nonsyndromic hearing loss 5	DISZ795Z	Strong	Genetic Variation	[1]
Hemochromatosis	DISAPY0H	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[3]
Stroke	DISX6UHX	moderate	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[4]
Peroxisome biogenesis disorder	DISBQ6QJ	Disputed	Genetic Variation	[5]
Chronic renal failure	DISGG7K6	Limited	Biomarker	[6]
End-stage renal disease	DISXA7GG	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleoporin NUP42 (NUP42).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nucleoporin NUP42 (NUP42).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nucleoporin NUP42 (NUP42).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleoporin NUP42 (NUP42).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nucleoporin NUP42 (NUP42).	[11]

References

• [1] Refined mapping of a gene for autosomal dominant progressive sensorineural hearing loss (DFNA5) to a 2-cM region, and exclusion of a candidate gene that is expressed in the cochlea.Eur J Hum Genet. 1997 Nov-Dec;5(6):397-405.
• [2] Localization of seven new genes around the HLA-A locus.Hum Mol Genet. 1993 Jan;2(1):55-60. doi: 10.1093/hmg/2.1.55.
• [3] A genome-wide association study of chronic obstructive pulmonary disease in Hispanics.Ann Am Thorac Soc. 2015 Mar;12(3):340-8. doi: 10.1513/AnnalsATS.201408-380OC.
• [4] Clinical and molecular epidemiology of community-onset, extended-spectrum beta-lactamase-producing Escherichia coli infections in Thailand: a case-case-control study.Am J Infect Control. 2007 Nov;35(9):606-12. doi: 10.1016/j.ajic.2007.05.008.
• [5] Peroxisome biogenesis and molecular defects in peroxisome assembly disorders.Cell Biochem Biophys. 2000;32 Spring:155-64. doi: 10.1385/cbb:32:1-3:155.
• [6] A grading system that predicts the risk of dialysis induction in IgA nephropathy patients based on the combination of the clinical and histological severity.Clin Exp Nephrol. 2019 Jan;23(1):16-25. doi: 10.1007/s10157-018-1657-0. Epub 2018 Oct 26.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.