General Information of Drug Off-Target (DOT) (ID: OT3PXV3H)

DOT Name DNA-directed RNA polymerases I, II, and III subunit RPABC4 (POLR2K)
Synonyms RNA polymerases I, II, and III subunit ABC4; ABC10-alpha; DNA-directed RNA polymerase II subunit K; RNA polymerase II 7.0 kDa subunit; RPB7.0; RPB10alpha
Gene Name POLR2K
Related Disease
Hepatocellular carcinoma ( )
UniProt ID
RPAB4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5IY6; 5IY7; 5IY8; 5IY9; 5IYA; 5IYB; 5IYC; 5IYD; 6DRD; 6O9L; 6XRE; 7A6H; 7AE1; 7AE3; 7AEA; 7AST; 7D58; 7D59; 7DN3; 7DU2; 7FJI; 7FJJ; 7LBM; 7OB9; 7OBA; 7OBB; 7VBA; 7VBB; 7VBC; 8A43; 8ITY; 8IUE; 8IUH
Pfam ID
PF03604
Sequence
MDTQKDVQPPKQQPMIYICGECHTENEIKSRDPIRCRECGYRIMYKKRTKRLVVFDAR
Function
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and a small RNAs, such as 5S rRNA and tRNAs, respectively.
KEGG Pathway
R. polymerase (hsa03020 )
Nucleotide excision repair (hsa03420 )
Cytosolic D.-sensing pathway (hsa04623 )
Huntington disease (hsa05016 )
Reactome Pathway
Formation of the Early Elongation Complex (R-HSA-113418 )
Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152 )
Formation of the HIV-1 Early Elongation Complex (R-HSA-167158 )
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection (R-HSA-167160 )
HIV Transcription Initiation (R-HSA-167161 )
RNA Polymerase II HIV Promoter Escape (R-HSA-167162 )
Transcription of the HIV genome (R-HSA-167172 )
Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200 )
Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238 )
Abortive elongation of HIV-1 transcript in the absence of Tat (R-HSA-167242 )
Tat-mediated HIV elongation arrest and recovery (R-HSA-167243 )
Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246 )
HIV elongation arrest and recovery (R-HSA-167287 )
Pausing and recovery of HIV elongation (R-HSA-167290 )
Viral Messenger RNA Synthesis (R-HSA-168325 )
Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949 )
MicroRNA (miRNA) biogenesis (R-HSA-203927 )
NoRC negatively regulates rRNA expression (R-HSA-427413 )
B-WICH complex positively regulates rRNA expression (R-HSA-5250924 )
Transcriptional regulation by small RNAs (R-HSA-5578749 )
PIWI-interacting RNA (piRNA) biogenesis (R-HSA-5601884 )
Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472 )
RNA Polymerase II Pre-transcription Events (R-HSA-674695 )
Formation of TC-NER Pre-Incision Complex (R-HSA-6781823 )
Transcription-Coupled Nucleotide Excision Repair (TC-NER) (R-HSA-6781827 )
Dual incision in TC-NER (R-HSA-6782135 )
Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210 )
TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648 )
FGFR2 alternative splicing (R-HSA-6803529 )
RNA polymerase II transcribes snRNA genes (R-HSA-6807505 )
mRNA Capping (R-HSA-72086 )
mRNA Splicing - Major Pathway (R-HSA-72163 )
mRNA Splicing - Minor Pathway (R-HSA-72165 )
Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203 )
RNA Polymerase I Transcription Initiation (R-HSA-73762 )
RNA Polymerase I Promoter Escape (R-HSA-73772 )
RNA Polymerase II Promoter Escape (R-HSA-73776 )
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening (R-HSA-73779 )
RNA Polymerase III Chain Elongation (R-HSA-73780 )
RNA Polymerase I Transcription Termination (R-HSA-73863 )
RNA Polymerase III Transcription Termination (R-HSA-73980 )
RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476 )
RNA Polymerase II Transcription Initiation (R-HSA-75953 )
RNA Polymerase II Transcription Elongation (R-HSA-75955 )
RNA Polymerase II Transcription Initiation And Promoter Clearance (R-HSA-76042 )
RNA Polymerase III Transcription Initiation From Type 1 Promoter (R-HSA-76061 )
RNA Polymerase III Transcription Initiation From Type 2 Promoter (R-HSA-76066 )
RNA Polymerase III Transcription Initiation From Type 3 Promoter (R-HSA-76071 )
RNA Pol II CTD phosphorylation and interaction with CE (R-HSA-77075 )
Signaling by FGFR2 IIIa TM (R-HSA-8851708 )
Estrogen-dependent gene expression (R-HSA-9018519 )
Inhibition of DNA recombination at telomere (R-HSA-9670095 )
Formation of RNA Pol II elongation complex (R-HSA-112382 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hepatocellular carcinoma DIS0J828 Strong Biomarker [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 DNA-directed RNA polymerases I, II, and III subunit RPABC4 (POLR2K). [2]
Selenium DM25CGV Approved Selenium decreases the expression of DNA-directed RNA polymerases I, II, and III subunit RPABC4 (POLR2K). [3]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of DNA-directed RNA polymerases I, II, and III subunit RPABC4 (POLR2K). [4]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of DNA-directed RNA polymerases I, II, and III subunit RPABC4 (POLR2K). [5]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of DNA-directed RNA polymerases I, II, and III subunit RPABC4 (POLR2K). [6]
------------------------------------------------------------------------------------

References

1 Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray.Oncol Rep. 2007 Oct;18(4):943-51.
2 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.
3 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
4 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
5 Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
6 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.