Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPZH72U)

• DOT Name: Nucleoporin Nup37 (NUP37)
• Synonyms: p37; Nup107-160 subcomplex subunit Nup37
• Gene Name: NUP37
• Related Disease:
  Gastric cancer
  Hepatocellular carcinoma
  Narcolepsy
  Stomach cancer
  Lyme disease
  Familial idiopathic steroid-resistant nephrotic syndrome
  Nephrotic syndrome, type 2
  Advanced cancer
  Nephrotic syndrome
  Schizophrenia
• UniProt ID: NUP37_HUMAN
• PDB ID: 5A9Q; 7PEQ; 7R5J; 7R5K
• Pfam ID: PF00400
• Sequence:
  MKQDASRNAAYTVDCEDYVHVVEFNPFENGDSGNLIAYGGNNYVVIGTCTFQEEEADVEG
  IQYKTLRTFHHGVRVDGIAWSPETRLDSLPPVIKFCTSAADMKIRLFTSDLQDKNEYKVL
  EGHTDFINGLVFDPKEGQEIASVSDDHTCRIWNLEGVQTAHFVLHSPGMSVCWHPEETFK
  LMVAEKNGTIRFYDLLAQQAILSLESEQVPLMSAHWCLKNTFKVGAVAGNDWLIWDITRS
  SYPQNKRPVHMDRACLFRWSTISENLFATTGYPGKMASQFQIHHLGHPQPILMGSVAVGS
  GLSWHRTLPLCVIGGDHKLLFWVTEV
• Function: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation.
• 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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[3]
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]
Lyme disease	DISO70G5	moderate	Biomarker	[4]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[5]
Nephrotic syndrome, type 2	DISIRFO1	Disputed	GermlineCausalMutation	[5]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[6]
Nephrotic syndrome	DISSPSC2	Limited	Biomarker	[5]
Schizophrenia	DISSRV2N	Limited	Biomarker	[7]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Nucleoporin Nup37 (NUP37) decreases the response to substance of Arsenic trioxide.	[17]

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 Nucleoporin Nup37 (NUP37).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nucleoporin Nup37 (NUP37).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nucleoporin Nup37 (NUP37).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nucleoporin Nup37 (NUP37).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nucleoporin Nup37 (NUP37).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nucleoporin Nup37 (NUP37).	[12]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Nucleoporin Nup37 (NUP37).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nucleoporin Nup37 (NUP37).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nucleoporin Nup37 (NUP37).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nucleoporin Nup37 (NUP37).	[16]

References

• [1] Mycoplasma hyorhinis infection in gastric carcinoma and its effects on the malignant phenotypes of gastric cancer cells.BMC Gastroenterol. 2010 Nov 10;10:132. doi: 10.1186/1471-230X-10-132.
• [2] Mycoplasma infection promotes tumor progression via interaction of the mycoplasmal protein p37 and epithelial cell adhesion molecule in hepatocellular carcinoma.Cancer Lett. 2019 Jul 10;454:44-52. doi: 10.1016/j.canlet.2019.04.007. Epub 2019 Apr 10.
• [3] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [4] The Borrelia burgdorferi 37-kilodalton immunoblot band (P37) used in serodiagnosis of early lyme disease is the flaA gene product.J Clin Microbiol. 1999 Mar;37(3):548-52. doi: 10.1128/JCM.37.3.548-552.1999.
• [5] 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.
• [6] Mapping of a Mycoplasma-Neutralizing Epitope on the Mycoplasmal p37 Protein.PLoS One. 2016 Dec 30;11(12):e0169091. doi: 10.1371/journal.pone.0169091. eCollection 2016.
• [7] Transcription of PIK3CD in human brain and schizophrenia: regulation by proinflammatory cytokines.Hum Mol Genet. 2019 Oct 1;28(19):3188-3198. doi: 10.1093/hmg/ddz144.
• [8] 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.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [13] Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.