Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTC294HE)

• DOT Name: Nuclear pore complex protein Nup133 (NUP133)
• Synonyms: 133 kDa nucleoporin; Nucleoporin Nup133
• Gene Name: NUP133
• Related Disease:
  Cystic kidney disease
  Galloway-Mowat syndrome 8
  Isolated congenital microcephaly
  Plasma cell myeloma
  Familial idiopathic steroid-resistant nephrotic syndrome
  Galloway-Mowat syndrome
  Nephrotic syndrome, type 2
  Nephrotic syndrome
  Nephrotic syndrome, type 18
• UniProt ID: NU133_HUMAN
• PDB ID: 1XKS; 3CQC; 3CQG; 3I4R; 5A9Q; 7PEQ; 7R5J; 7R5K
• Pfam ID: PF03177
• Sequence:
  MFPAAPSPRTPGTGSRRGPLAGLGPGSTPRTASRKGLPLGSAVSSPVLFSPVGRRSSLSS
  RGTPTRMFPHHSITESVNYDVKTFGSSLPVKVMEALTLAEVDDQLTINIDEGGWACLVCK
  EKLIIWKIALSPITKLSVCKELQLPPSDFHWSADLVALSYSSPSGEAHSTQAVAVMVATR
  EGSIRYWPSLAGEDTYTEAFVDSGGDKTYSFLTAVQGGSFILSSSGSQLIRLIPESSGKI
  HQHILPQGQGMLSGIGRKVSSLFGILSPSSDLTLSSVLWDRERSSFYSLTSSNISKWELD
  DSSEKHAYSWDINRALKENITDAIWGSESNYEAIKEGVNIRYLDLKQNCDGLVILAAAWH
  SADNPCLIYYSLITIEDNGCQMSDAVTVEVTQYNPPFQSEDLILCQLTVPNFSNQTAYLY
  NESAVYVCSTGTGKFSLPQEKIVFNAQGDSVLGAGACGGVPIIFSRNSGLVSITSRENVS
  ILAEDLEGSLASSVAGPNSESMIFETTTKNETIAQEDKIKLLKAAFLQYCRKDLGHAQMV
  VDELFSSHSDLDSDSELDRAVTQISVDLMDDYPASDPRWAESVPEEAPGFSNTSLIILHQ
  LEDKMKAHSFLMDFIHQVGLFGRLGSFPVRGTPMATRLLLCEHAEKLSAAIVLKNHHSRL
  SDLVNTAILIALNKREYEIPSNLTPADVFFREVSQVDTICECLLEHEEQVLRDAPMDSIE
  WAEVVINVNNILKDMLQAASHYRQNRNSLYRREESLEKEPEYVPWTATSGPGGIRTVIIR
  QHEIVLKVAYPQADSNLRNIVTEQLVALIDCFLDGYVSQLKSVDKSSNRERYDNLEMEYL
  QKRSDLLSPLLSLGQYLWAASLAEKYCDFDILVQMCEQTDNQSRLQRYMTQFADQNFSDF
  LFRWYLEKGKRGKLLSQPISQHGQLANFLQAHEHLSWLHEINSQELEKAHATLLGLANME
  TRYFAKKKTLLGLSKLAALASDFSEDMLQEKIEEMAEQERFLLHQETLPEQLLAEKQLNL
  SAMPVLTAPQLIGLYICEENRRANEYDFKKALDLLEYIDEEEDININDLKLEILCKALQR
  DNWSSSDGKDDPIEVSKDSIFVKILQKLLKDGIQLSEYLPEVKDLLQADQLGSLKSNPYF
  EFVLKANYEYYVQGQI
• Function: Involved in poly(A)+ RNA transport. Involved in nephrogenesis.
• Tissue Specificity: Widely expressed in fetal and adult tissues. Expressed in the brain and kidney.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  Amyotrophic lateral sclerosis (hsa05014)
• Reactome Pathway:
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)
  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)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  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)
  RHO GTPases Activate Formins (R-HSA-5663220)
  tRNA processing in the nucleus (R-HSA-6784531)
  Mitotic Prometaphase (R-HSA-68877)
  HCMV Early Events (R-HSA-9609690)
  HCMV Late Events (R-HSA-9610379)
  Postmitotic nuclear pore complex (NPC) reformation (R-HSA-9615933)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  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

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic kidney disease	DISRT1LM	Strong	Biomarker	[1]
Galloway-Mowat syndrome 8	DISSH64O	Strong	Autosomal recessive	[2]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[2]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[3]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[4]
Galloway-Mowat syndrome	DISVB7IM	Supportive	Autosomal recessive	[2]
Nephrotic syndrome, type 2	DISIRFO1	Disputed	GermlineCausalMutation	[4]
Nephrotic syndrome	DISSPSC2	Limited	Altered Expression	[1]
Nephrotic syndrome, type 18	DISKTVM3	Limited	Unknown	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Nuclear pore complex protein Nup133 (NUP133).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nuclear pore complex protein Nup133 (NUP133).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[14]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Nuclear pore complex protein Nup133 (NUP133).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Nuclear pore complex protein Nup133 (NUP133).	[13]

References

• [1] Moderate Nucleoporin 133 deficiency leads to glomerular damage in zebrafish.Sci Rep. 2019 Mar 18;9(1):4750. doi: 10.1038/s41598-019-41202-4.
• [2] Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome. Ann Neurol. 2018 Dec;84(6):814-828. doi: 10.1002/ana.25370.
• [3] High expression of nucleoporin 133 mRNA in bone marrow CD138+ cells is a poor prognostic factor in multiple myeloma.Oncotarget. 2018 May 18;9(38):25127-25135. doi: 10.18632/oncotarget.25350. eCollection 2018 May 18.
• [4] Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome. J Clin Invest. 2018 Oct 1;128(10):4313-4328. doi: 10.1172/JCI98688. Epub 2018 Sep 4.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene. 2001 Jan 10;262(1-2):207-14. doi: 10.1016/s0378-1119(00)00530-8.
• [10] 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.
• [11] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [12] 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.
• [13] 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.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [15] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.