Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3BLQ9M)

• DOT Name: Nuclear pore membrane glycoprotein 210 (NUP210)
• Synonyms: Nuclear pore protein gp210; Nuclear envelope pore membrane protein POM 210; POM210; Nucleoporin Nup210; Pore membrane protein of 210 kDa
• Gene Name: NUP210
• Related Disease:
  Colorectal carcinoma
  Endometriosis
  Liver cirrhosis
  Lung adenocarcinoma
  Myocardial infarction
  Primary biliary cholangitis
  Coronary heart disease
  Type-1 diabetes
  Liver failure
  Schizophrenia
• UniProt ID: PO210_HUMAN
• PDB ID: 7R5J; 7R5K
• Pfam ID: PF02368
• Sequence:
  MAARGRGLLLLTLSVLLAAGPSAAAAKLNIPKVLLPFTRATRVNFTLEASEGCYRWLSTR
  PEVASIEPLGLDEQQCSQKAVVQARLTQPARLTSIIFAEDITTGQVLRCDAIVDLIHDIQ
  IVSTTRELYLEDSPLELKIQALDSEGNTFSTLAGLVFEWTIVKDSEADRFSDSHNALRIL
  TFLESTYIPPSYISEMEKAAKQGDTILVSGMKTGSSKLKARIQEAVYKNVRPAEVRLLIL
  ENILLNPAYDVYLMVGTSIHYKVQKIRQGKITELSMPSDQYELQLQNSIPGPEGDPARPV
  AVLAQDTSMVTALQLGQSSLVLGHRSIRMQGASRLPNSTIYVVEPGYLGFTVHPGDRWVL
  ETGRLYEITIEVFDKFSNKVYVSDNIRIETVLPAEFFEVLSSSQNGSYHRIRALKRGQTA
  IDAALTSVVDQDGGVHILQVPVWNQQEVEIHIPITLYPSILTFPWQPKTGAYQYTIRAHG
  GSGNFSWSSSSHLVATVTVKGVMTTGSDIGFSVIQAHDVQNPLHFGEMKVYVIEPHSMEF
  APCQVEARVGQALELPLRISGLMPGGASEVVTLSDCSHFDLAVEVENQGVFQPLPGRLPP
  GSEHCSGIRVKAEAQGSTTLLVSYRHGHVHLSAKITIAAYLPLKAVDPSSVALVTLGSSK
  EMLFEGGPRPWILEPSKFFQNVTAEDTDSIGLALFAPHSSRNYQQHWILVTCQALGEQVI
  ALSVGNKPSLTNPFPAVEPAVVKFVCAPPSRLTLAPVYTSPQLDMSCPLLQQNKQVVPVS
  SHRNPRLDLAAYDQEGRRFDNFSSLSIQWESTRPVLASIEPELPMQLVSQDDESGQKKLH
  GLQAILVHEASGTTAITATATGYQESHLSSARTKQPHDPLVPLSASIELILVEDVRVSPE
  EVTIYNHPGIQAELRIREGSGYFFLNTSTADVVKVAYQEARGVAMVHPLLPGSSTIMIHD
  LCLVFPAPAKAVVYVSDIQELYIRVVDKVEIGKTVKAYVRVLDLHKKPFLAKYFPFMDLK
  LRAASPIITLVALDEALDNYTITFLIRGVAIGQTSLTASVTNKAGQRINSAPQQIEVFPP
  FRLMPRKVTLLIGATMQVTSEGGPQPQSNILFSISNESVALVSAAGLVQGLAIGNGTVSG
  LVQAVDAETGKVVIISQDLVQVEVLLLRAVRIRAPIMRMRTGTQMPIYVTGITNHQNPFS
  FGNAVPGLTFHWSVTKRDVLDLRGRHHEASIRLPSQYNFAMNVLGRVKGRTGLRVVVKAV
  DPTSGQLYGLARELSDEIQVQVFEKLQLLNPEIEAEQILMSPNSYIKLQTNRDGAASLSY
  RVLDGPEKVPVVHVDEKGFLASGSMIGTSTIEVIAQEPFGANQTIIVAVKVSPVSYLRVS
  MSPVLHTQNKEALVAVPLGMTVTFTVHFHDNSGDVFHAHSSVLNFATNRDDFVQIGKGPT
  NNTCVVRTVSVGLTLLRVWDAEHPGLSDFMPLPVLQAISPELSGAMVVGDVLCLATVLTS
  LEGLSGTWSSSANSILHIDPKTGVAVARAVGSVTVYYEVAGHLRTYKEVVVSVPQRIMAR
  HLHPIQTSFQEATASKVIVAVGDRSSNLRGECTPTQREVIQALHPETLISCQSQFKPAVF
  DFPSQDVFTVEPQFDTALGQYFCSITMHRLTDKQRKHLSMKKTALVVSASLSSSHFSTEQ
  VGAEVPFSPGLFADQAEILLSNHYTSSEIRVFGAPEVLENLEVKSGSPAVLAFAKEKSFG
  WPSFITYTVGVLDPAAGSQGPLSTTLTFSSPVTNQAIAIPVTVAFVVDRRGPGPYGASLF
  QHFLDSYQVMFFTLFALLAGTAVMIIAYHTVCTPRDLAVPAALTPRASPGHSPHYFAASS
  PTSPNALPPARKASPPSGLWSPAYASH
• Function: Nucleoporin essential for nuclear pore assembly and fusion, nuclear pore spacing, as well as structural integrity.
• Tissue Specificity: Ubiquitous expression, with highest levels in lung, liver, pancreas, testis, and ovary, intermediate levels in brain, kidney, and spleen, and lowest levels in heart and skeletal muscle.
• 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)
  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
Colorectal carcinoma	DIS5PYL0	Definitive	Genetic Variation	[1]
Endometriosis	DISX1AG8	Strong	Genetic Variation	[2]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[5]
Primary biliary cholangitis	DIS43E0O	Strong	Biomarker	[6]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[7]
Type-1 diabetes	DIS7HLUB	moderate	Genetic Variation	[7]
Liver failure	DISLGEL6	Limited	Biomarker	[8]
Schizophrenia	DISSRV2N	No Known	Unknown	[9]

17 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 Nuclear pore membrane glycoprotein 210 (NUP210).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[16]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[17]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[19]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[20]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[26]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Nuclear pore membrane glycoprotein 210 (NUP210).	[27]

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 decreases the phosphorylation of Nuclear pore membrane glycoprotein 210 (NUP210).	[24]

References

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• [2] Functional polymorphism within NUP210 encoding for nucleoporin GP210 is associated with the risk of endometriosis.Fertil Steril. 2019 Aug;112(2):343-352.e1. doi: 10.1016/j.fertnstert.2019.04.011. Epub 2019 Jun 27.
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• [18] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [19] 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.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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• [24] 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.
• [25] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
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