Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG4RDYS)

• DOT Name: Nuclear pore complex protein Nup107 (NUP107)
• Synonyms: 107 kDa nucleoporin; Nucleoporin Nup107
• Gene Name: NUP107
• Related Disease:
  Female hypogonadism
  Cervical cancer
  Epithelial ovarian cancer
  Focal segmental glomerulosclerosis
  Galloway-Mowat syndrome 7
  Neoplasm
  Nephrotic syndrome, type 11
  Nephrotic syndrome, type 2
  Ovarian cancer
  Ovarian dysgenesis 1
  Ovarian dysgenesis 6
  Ovarian neoplasm
  Steroid-resistant nephrotic syndrome
  Gonadal dysgenesis
  46 XX gonadal dysgenesis
  Familial idiopathic steroid-resistant nephrotic syndrome
  Galloway-Mowat syndrome
  Adenocarcinoma
  Amyotrophic lateral sclerosis
  Nephrotic syndrome
• UniProt ID: NU107_HUMAN
• PDB ID: 3CQC; 3CQG; 3I4R; 5A9Q; 7PEQ; 7R5J; 7R5K
• Pfam ID: PF04121
• Sequence:
  MDRSGFGEISSPVIREAEVTRTARKQSAQKRVLLQASQDENFGNTTPRNQVIPRTPSSFR
  QPFTPTSRSLLRQPDISCILGTGGKSPRLTQSSGFFGNLSMVTNLDDSNWAAAFSSQRSG
  LFTNTEPHSITEDVTISAVMLREDDPGEAASMSMFSDFLQSFLKHSSSTVFDLVEEYENI
  CGSQVNILSKIVSRATPGLQKFSKTASMLWLLQQEMVTWRLLASLYRDRIQSALEEESVF
  AVTAVNASEKTVVEALFQRDSLVRQSQLVVDWLESIAKDEIGEFSDNIEFYAKSVYWENT
  LHTLKQRQLTSYVGSVRPLVTELDPDAPIRQKMPLDDLDREDEVRLLKYLFTLIRAGMTE
  EAQRLCKRCGQAWRAATLEGWKLYHDPNVNGGTELEPVEGNPYRRIWKISCWRMAEDELF
  NRYERAIYAALSGNLKQLLPVCDTWEDTVWAYFRVMVDSLVEQEIQTSVATLDETEELPR
  EYLGANWTLEKVFEELQATDKKRVLEENQEHYHIVQKFLILGDIDGLMDEFSKWLSKSRN
  NLPGHLLRFMTHLILFFRTLGLQTKEEVSIEVLKTYIQLLIREKHTNLIAFYTCHLPQDL
  AVAQYALFLESVTEFEQRHHCLELAKEADLDVATITKTVVENIRKKDNGEFSHHDLAPAL
  DTGTTEEDRLKIDVIDWLVFDPAQRAEALKQGNAIMRKFLASKKHEAAKEVFVKIPQDSI
  AEIYNQCEEQGMESPLPAEDDNAIREHLCIRAYLEAHETFNEWFKHMNSVPQKPALIPQP
  TFTEKVAHEHKEKKYEMDFGIWKGHLDALTADVKEKMYNVLLFVDGGWMVDVREDAKEDH
  ERTHQMVLLRKLCLPMLCFLLHTILHSTGQYQECLQLADMVSSERHKLYLVFSKEELRKL
  LQKLRESSLMLLDQGLDPLGYEIQL
• Function: Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. Required for the assembly of peripheral proteins into the NPC. May anchor NUP62 to the NPC. Involved in nephrogenesis.
• Tissue Specificity: Ubiquitously expressed in fetal and adult tissues.
• 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

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Female hypogonadism	DISWASB4	Definitive	Biomarker	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[3]
Focal segmental glomerulosclerosis	DISJNHH0	Strong	Genetic Variation	[4]
Galloway-Mowat syndrome 7	DISESCC3	Strong	Autosomal recessive	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Nephrotic syndrome, type 11	DISXG30I	Strong	Autosomal recessive	[6]
Nephrotic syndrome, type 2	DISIRFO1	Strong	GermlineCausalMutation	[7]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[3]
Ovarian dysgenesis 1	DISXIXHW	Strong	GermlineCausalMutation	[1]
Ovarian dysgenesis 6	DISLK2RR	Strong	Autosomal recessive	[8]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[3]
Steroid-resistant nephrotic syndrome	DISVEBC9	Strong	Genetic Variation	[9]
Gonadal dysgenesis	DISIL2ZI	moderate	Biomarker	[1]
46 XX gonadal dysgenesis	DISBB9HA	Supportive	Autosomal dominant	[1]
Familial idiopathic steroid-resistant nephrotic syndrome	DISQ53RS	Supportive	Autosomal dominant	[7]
Galloway-Mowat syndrome	DISVB7IM	Supportive	Autosomal recessive	[10]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[11]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[12]
Nephrotic syndrome	DISSPSC2	Limited	Genetic Variation	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Nuclear pore complex protein Nup107 (NUP107).	[14]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nuclear pore complex protein Nup107 (NUP107).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[19]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nuclear pore complex protein Nup107 (NUP107).	[20]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Nuclear pore complex protein Nup107 (NUP107).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[22]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Nuclear pore complex protein Nup107 (NUP107).	[23]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[24]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear pore complex protein Nup107 (NUP107).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nuclear pore complex protein Nup107 (NUP107).	[18]

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 Nuclear pore complex protein Nup107 (NUP107).	[27]

References

• [1] A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis. J Clin Invest. 2015 Nov 2;125(11):4295-304. doi: 10.1172/JCI83553. Epub 2015 Oct 20.
• [2] Nucleoporin 107 Promotes the Survival of Tumor Cells in Cervical Cancers.Gynecol Obstet Invest. 2020;85(1):41-52. doi: 10.1159/000502788. Epub 2019 Sep 5.
• [3] Single nucleotide variant in Nucleoporin 107 may be predictive of sensitivity to chemotherapy in patients with ovarian cancer.Pharmacogenet Genomics. 2017 Jul;27(7):264-269. doi: 10.1097/FPC.0000000000000288.
• [4] NUP107 mutations in children with steroid-resistant nephrotic syndrome.Nephrol Dial Transplant. 2017 Jun 1;32(6):1013-1017. doi: 10.1093/ndt/gfw103.
• [5] [Socialization of the nursing function. Development of the system of home nursing and home nursing seminars for the public]. Kango Tenbo. 1977 Mar;2(3):67-75.
• [6] Neonatal case history. Lamp. 1978 Aug;35(8):4-10.
• [7] Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome. Am J Hum Genet. 2015 Oct 1;97(4):555-66. doi: 10.1016/j.ajhg.2015.08.013. Epub 2015 Sep 24.
• [8] [The patient in the juridical relationship: observations on patients' rights]. Tijdschr Ziekenverpl. 1978 Oct 3;31(20):905-14.
• [9] Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome. Ann Neurol. 2018 Dec;84(6):814-828. doi: 10.1002/ana.25370.
• [10] Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome. J Med Genet. 2017 Jun;54(6):399-403. doi: 10.1136/jmedgenet-2016-104237. Epub 2017 Mar 9.
• [11] Isolation and characterization of human lung cancer antigens by serological screening with autologous antibodies.Cancer Lett. 2011 Feb 1;301(1):57-62. doi: 10.1016/j.canlet.2010.10.024. Epub 2010 Nov 20.
• [12] Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat.J Neurosci Res. 2017 Sep;95(9):1745-1759. doi: 10.1002/jnr.24005. Epub 2016 Dec 28.
• [13] 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.
• [14] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [19] 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.
• [20] 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.
• [21] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [22] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [23] 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.
• [24] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [25] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [26] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [27] 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.