Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1NJK2)

DOT Name Protein RRP5 homolog (PDCD11)
Synonyms NF-kappa-B-binding protein; NFBP; Programmed cell death protein 11
Gene Name PDCD11
Related Disease
Primary cutaneous T-cell lymphoma ( )
High blood pressure ( )
Stroke ( )
Type-1/2 diabetes ( )
UniProt ID
RRP5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1WI5
Pfam ID
PF00575 ; PF05843
Sequence
MANLEESFPRGGTRKIHKPEKAFQQSVEQDNLFDISTEEGSTKRKKSQKGPAKTKKLKIE
KRESSKSAREKFEILSVESLCEGMRILGCVKEVNELELVISLPNGLQGFVQVTEICDAYT
KKLNEQVTQEQPLKDLLHLPELFSPGMLVRCVVSSLGITDRGKKSVKLSLNPKNVNRVLS
AEALKPGMLLTGTVSSLEDHGYLVDIGVDGTRAFLPLLKAQEYIRQKNKGAKLKVGQYLN
CIVEKVKGNGGVVSLSVGHSEVSTAIATEQQSWNLNNLLPGLVVKAQVQKVTPFGLTLNF
LTFFTGVVDFMHLDPKKAGTYFSNQAVRACILCVHPRTRVVHLSLRPIFLQPGRPLTRLS
CQNLGAVLDDVPVQGFFKKAGATFRLKDGVLAYARLSHLSDSKNVFNPEAFKPGNTHKCR
IIDYSQMDELALLSLRTSIIEAQYLRYHDIEPGAVVKGTVLTIKSYGMLVKVGEQMRGLV
PPMHLADILMKNPEKKYHIGDEVKCRVLLCDPEAKKLMMTLKKTLIESKLPVITCYADAK
PGLQTHGFIIRVKDYGCIVKFYNNVQGLVPKHELSTEYIPDPERVFYTGQVVKVVVLNCE
PSKERMLLSFKLSSDPEPKKEPAGHSQKKGKAINIGQLVDVKVLEKTKDGLEVAVLPHNI
RAFLPTSHLSDHVANGPLLHHWLQAGDILHRVLCLSQSEGRVLLCRKPALVSTVEGGQDP
KNFSEIHPGMLLIGFVKSIKDYGVFIQFPSGLSGLAPKAIMSDKFVTSTSDHFVEGQTVA
AKVTNVDEEKQRMLLSLRLSDCGLGDLAITSLLLLNQCLEELQGVRSLMSNRDSVLIQTL
AEMTPGMFLDLVVQEVLEDGSVVFSGGPVPDLVLKASRYHRAGQEVESGQKKKVVILNVD
LLKLEVHVSLHQDLVNRKARKLRKGSEHQAIVQHLEKSFAIASLVETGHLAAFSLTSHLN
DTFRFDSEKLQVGQGVSLTLKTTEPGVTGLLLAVEGPAAKRTMRPTQKDSETVDEDEEVD
PALTVGTIKKHTLSIGDMVTGTVKSIKPTHVVVTLEDGIIGCIHASHILDDVPEGTSPTT
KLKVGKTVTARVIGGRDMKTFKYLPISHPRFVRTIPELSVRPSELEDGHTALNTHSVSPM
EKIKQYQAGQTVTCFLKKYNVVKKWLEVEIAPDIRGRIPLLLTSLSFKVLKHPDKKFRVG
QALRATVVGPDSSKTLLCLSLTGPHKLEEGEVAMGRVVKVTPNEGLTVSFPFGKIGTVSI
FHMSDSYSETPLEDFVPQKVVRCYILSTADNVLTLSLRSSRTNPETKSKVEDPEINSIQD
IKEGQLLRGYVGSIQPHGVFFRLGPSVVGLARYSHVSQHSPSKKALYNKHLPEGKLLTAR
VLRLNHQKNLVELSFLPGDTGKPDVLSASLEGQLTKQEERKTEAEERDQKGEKKNQKRNE
KKNQKGQEEVEMPSKEKQQPQKPQAQKRGGRECRESGSEQERVSKKPKKAGLSEEDDSLV
DVYYREGKEEAEETNVLPKEKQTKPAEAPRLQLSSGFAWNVGLDSLTPALPPLAESSDSE
EDEKPHQATIKKSKKERELEKQKAEKELSRIEEALMDPGRQPESADDFDRLVLSSPNSSI
LWLQYMAFHLQATEIEKARAVAERALKTISFREEQEKLNVWVALLNLENMYGSQESLTKV
FERAVQYNEPLKVFLHLADIYAKSEKFQEAGELYNRMLKRFRQEKAVWIKYGAFLLRRSQ
AAASHRVLQRALECLPSKEHVDVIAKFAQLEFQLGDAERAKAIFENTLSTYPKRTDVWSV
YIDMTIKHGSQKDVRDIFERVIHLSLAPKRMKFFFKRYLDYEKQHGTEKDVQAVKAKALE
YVEAKSSVLED
Function Essential for the generation of mature 18S rRNA, specifically necessary for cleavages at sites A0, 1 and 2 of the 47S precursor. Directly interacts with U3 snoRNA; Involved in the biogenesis of rRNA.
Reactome Pathway
Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226 )
rRNA modification in the nucleus and cytosol (R-HSA-6790901 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Primary cutaneous T-cell lymphoma DIS35WVW Definitive Biomarker [1]
High blood pressure DISY2OHH Disputed Genetic Variation [2]
Stroke DISX6UHX Disputed Biomarker [2]
Type-1/2 diabetes DISIUHAP Disputed Genetic Variation [2]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 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 Protein RRP5 homolog (PDCD11). [3]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Protein RRP5 homolog (PDCD11). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Protein RRP5 homolog (PDCD11). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Protein RRP5 homolog (PDCD11). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Protein RRP5 homolog (PDCD11). [7]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Protein RRP5 homolog (PDCD11). [8]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Protein RRP5 homolog (PDCD11). [9]
Clozapine DMFC71L Approved Clozapine increases the expression of Protein RRP5 homolog (PDCD11). [9]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial decreases the expression of Protein RRP5 homolog (PDCD11). [10]
Motexafin gadolinium DMEJKRF Approved Motexafin gadolinium decreases the expression of Protein RRP5 homolog (PDCD11). [10]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Protein RRP5 homolog (PDCD11). [7]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Protein RRP5 homolog (PDCD11). [13]
------------------------------------------------------------------------------------
⏷ Show the Full List of 12 Drug(s)
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Protein RRP5 homolog (PDCD11). [11]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Protein RRP5 homolog (PDCD11). [12]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Protein RRP5 homolog (PDCD11). [12]
------------------------------------------------------------------------------------

References

1 The human Exonuclease-1 interactome and phosphorylation sites.Biochem Biophys Res Commun. 2019 Jun 30;514(3):567-573. doi: 10.1016/j.bbrc.2019.04.171. Epub 2019 May 2.
2 Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack.Oncotarget. 2017 Dec 24;9(10):8836-8848. doi: 10.18632/oncotarget.23653. eCollection 2018 Feb 6.
3 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.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 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.
6 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.
7 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.
8 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.
9 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
10 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
11 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
12 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.
13 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.