Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIA7ZOQ)

DOT Name Nuclear envelope pore membrane protein POM 121 (POM121)
Synonyms Nuclear envelope pore membrane protein POM 121A; Nucleoporin Nup121; Pore membrane protein of 121 kDa
Gene Name POM121
Related Disease
Prostate cancer ( )
Prostate carcinoma ( )
Neuroblastoma ( )
Prader-Willi syndrome ( )
Squamous cell carcinoma ( )
UniProt ID
P121A_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5T6W
Pfam ID
PF15229
Sequence
MSPAAAAAGAGERRRPIASVRDGRGRGCGGPARAVLLGLSLVGLLLYLVPAAAALAWLTV
GATAAWWGLSREPRGSRPLSSFVRKARHRRPLSSFVRKARHRRTLFASPLAKSTANGNLL
EPRTLLEGPDPAELLLMGSYLGKPGPPQPAAAPEGQDLRDRPGRRPPARPAPRSPPPRSP
PPRSPPPSPPTHRAHHVYPSLPTPLLRPSRRPSPRDCGTLPNRFVITPRRRYPIHQAQYS
CLGVLPTVCWNGYHKKAVLSPRNSRMVCSPVTVRIAPPDRRFSRSAIPEQIISSTLSSPS
SNAPDPCAKETVLSALKEKEKKRTVEEEDQIFLDGQENKRRRHDSSGSGHSAFEPLVANG
VPASFVPKPGSLKRGLNSQSSDDHLNKRSRSSSMSSLTGAYASGIPSSSRNAITSSYSST
RGISQLWKRNGPSSSPFSSPASSRSQTPERPAKKIREEELCHHSSSSTPLAADRESQGEK
AADTTPRKKQNSNSQSTPGSSGQRKRKVQLLPSRRGEQLTLPPPPQLGYSITAEDLDLEK
KASLQWFNQALEDKSDAASNSVTETPPITQPSFTFTLPAAAPASPPTSLLAPSTNPLLES
LKKMQTPPSLPPCPESAGAATTEALSPPKTPSLLPPLGLSQSGPPGLLPSPSFDSKPPTT
LLGLIPAPSMVPATDTKAPPTLQAETATKPQATSAPSPAPKQSFLFGTQNTSPSSPAAPA
ASSAPPMFKPIFTAPPKSEKEGPTPPGPSVTATAPSSSSLPTTTSTTAPTFQPVFSSMGP
PASVPLPAPFFKQTTTPATAPTTTAPLFTGLASATSAVAPITSASPSTDSASKPAFGFGI
NSVSSSSVSTTTSTATAASQPFLFGAPQASAASFTPAMGSIFQFGKPPALPTTTTVTTFS
QSLHTAVPTATSSSAADFSGFGSTLATSAPATSSQPTLTFSNTSTPTFNIPFGSSAKSPL
PSYPGANPQPAFGAAEGQPPGAAKPALAPSFGSSFTFGNSAAPAAAPTPAPPSMIKVVPA
YVPTPIHPIFGGATHSAFGLKATASAFGAPASSQPAFGGSTAVFFGAATSSGFGATTQTA
SSGSSSSVFGSTTPSPFTFGGSAAPAGSGSFGINVATPGSSTTTGAFSFGAGQSGSTATS
TPFAGGLGQNALGTTGQSTPFAFNVSSTTESKPVFGGTATPTFGLNTPAPGVGTSGSSLS
FGASSAPAQGFVGVAPFGSAALSFSIGAGSKTPGARQRLQARRQHTRKK
Function
Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL).
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

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Prostate cancer DISF190Y Strong Biomarker [1]
Prostate carcinoma DISMJPLE Strong Biomarker [1]
Neuroblastoma DISVZBI4 moderate Altered Expression [2]
Prader-Willi syndrome DISYWMLU moderate Biomarker [3]
Squamous cell carcinoma DISQVIFL Limited Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Nuclear envelope pore membrane protein POM 121 (POM121). [5]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Nuclear envelope pore membrane protein POM 121 (POM121). [9]
Quercetin DM3NC4M Approved Quercetin decreases the phosphorylation of Nuclear envelope pore membrane protein POM 121 (POM121). [10]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Nuclear envelope pore membrane protein POM 121 (POM121). [10]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Nuclear envelope pore membrane protein POM 121 (POM121). [10]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Nuclear envelope pore membrane protein POM 121 (POM121). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Nuclear envelope pore membrane protein POM 121 (POM121). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Nuclear envelope pore membrane protein POM 121 (POM121). [8]
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References

1 Targeting Nucleoporin POM121-Importin Axis in Prostate Cancer.Cell Chem Biol. 2018 Sep 20;25(9):1056-1058. doi: 10.1016/j.chembiol.2018.09.003.
2 Noninvasive monitoring of apoptosis versus necrosis in a neuroblastoma cell line expressing a nuclear pore protein tagged with the green fluorescent protein.Exp Cell Res. 1998 Feb 1;238(2):371-6. doi: 10.1006/excr.1997.3846.
3 The imprinted NPAP1 gene in the Prader-Willi syndrome region belongs to a POM121-related family of retrogenes.Genome Biol Evol. 2014 Feb;6(2):344-51. doi: 10.1093/gbe/evu019.
4 POM121 is identified as a novel prognostic marker of oral squamous cell carcinoma.J Cancer. 2019 Jul 24;10(19):4473-4480. doi: 10.7150/jca.33368. eCollection 2019.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 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.
7 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
8 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
9 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
10 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.