Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF2GQC1)

• DOT Name: Nucleoporin NDC1 (NDC1)
• Synonyms: hNDC1; Transmembrane protein 48
• Gene Name: NDC1
• Related Disease:
  Lung carcinoma
  Advanced cancer
  Lung cancer
  Neoplasm
  Non-small-cell lung cancer
  Meningioma
• UniProt ID: NDC1_HUMAN
• PDB ID: 7R5J; 7R5K
• Pfam ID: PF09531
• Sequence:
  MATAVSRPCAGRSRDILWRVLGWRIVASIVWSVLFLPICTTVFIIFSRIDLFHPIQWLSD
  SFSDLYSSYVIFYFLLLSVVIIIISIFNVEFYAVVPSIPCSRLALIGKIIHPQQLMHSFI
  HAAMGMVMAWCAAVITQGQYSFLVVPCTGTNSFGSPAAQTCLNEYHLFFLLTGAFMGYSY
  SLLYFVNNMNYLPFPIIQQYKFLRFRRSLLLLVKHSCVESLFLVRNFCILYYFLGYIPKA
  WISTAMNLHIDEQVHRPLDTVSGLLNLSLLYHVWLCGVFLLTTWYVSWILFKIYATEAHV
  FPVQPPFAEGSDECLPKVLNSNPPPIIKYLALQDLMLLSQYSPSRRQEVFSLSQPGGHPH
  NWTAISRECLNLLNGMTQKLILYQEAAATNGRVSSSYPVEPKKLNSPEETAFQTPKSSQM
  PRPSVPPLVKTSLFSSKLSTPDVVSPFGTPFGSSVMNRMAGIFDVNTCYGSPQSPQLIRR
  GPRLWTSASDQQMTEFSNPSPSTSISAEGKTMRQPSVIYSWIQNKREQIKNFLSKRVLIM
  YFFSKHPEASIQAVFSDAQMHIWALEGLSHLVAASFTEDRFGVVQTTLPAILNTLLTLQE
  AVDKYFKLPHASSKPPRISGSLVDTSYKTLRFAFRASLKTAIYRITTTFGEHLNAVQASA
  EHQKRLQQFLEFKE
• Function: Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung carcinoma	DISTR26C	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Meningioma	DISPT4TG	moderate	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nucleoporin NDC1 (NDC1).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nucleoporin NDC1 (NDC1).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleoporin NDC1 (NDC1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleoporin NDC1 (NDC1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nucleoporin NDC1 (NDC1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleoporin NDC1 (NDC1).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Nucleoporin NDC1 (NDC1).	[11]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Nucleoporin NDC1 (NDC1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nucleoporin NDC1 (NDC1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Nucleoporin NDC1 (NDC1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nucleoporin NDC1 (NDC1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Nucleoporin NDC1 (NDC1).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nucleoporin NDC1 (NDC1).	[19]

3 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 Nucleoporin NDC1 (NDC1).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Nucleoporin NDC1 (NDC1).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nucleoporin NDC1 (NDC1).	[15]

References

• [1] TMEM Proteins in Cancer: A Review.Front Pharmacol. 2018 Dec 6;9:1345. doi: 10.3389/fphar.2018.01345. eCollection 2018.
• [2] miRNA-mediated apoptosis activation through TMEM 48 inhibition in A549 cell line.Biochem Biophys Res Commun. 2018 Sep 3;503(1):323-329. doi: 10.1016/j.bbrc.2018.06.023. Epub 2018 Jun 14.
• [3] Overexpression and biological function of TMEM48 in non-small cell lung carcinoma.Tumour Biol. 2016 Feb;37(2):2575-86. doi: 10.1007/s13277-015-4014-x. Epub 2015 Sep 21.
• [4] A comparison of the prevalence and risk factors of complications in intracranial tumor embolization between the Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and JR-NET3.Acta Neurochir (Wien). 2019 Aug;161(8):1675-1682. doi: 10.1007/s00701-019-03970-w. Epub 2019 Jun 7.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] 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.
• [8] 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.
• [9] 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.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [15] 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.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.