Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTB5SV7)

• DOT Name: Polymerase delta-interacting protein 3 (POLDIP3)
• Synonyms: 46 kDa DNA polymerase delta interaction protein; p46; S6K1 Aly/REF-like target; SKAR
• Gene Name: POLDIP3
• Related Disease:
  Subarachnoid hemorrhage
  Advanced cancer
  Disorder of glycogen metabolism
  Gastric cancer
  Gerstmann-Straussler-Scheinker syndrome
  Hepatitis C virus infection
  Metabolic disorder
  Stomach cancer
  Autosomal dominant prognathism
  Hepatocellular carcinoma
  Amyotrophic lateral sclerosis
• UniProt ID: PDIP3_HUMAN
• Pfam ID: PF00076
• Sequence:
  MADISLDELIRKRGAAAKGRLNARPGVGGVRSRVGIQQGLLSQSTRTATFQQRFDARQKI
  GLSDARLKLGVKDAREKLLQKDARFRIKGKVQDAREMLNSRKQQTTVPQKPRQVADAREK
  ISLKRSSPAAFINPPIGTVTPALKLTKTIQVPQQKAMAPLHPHPAGMRINVVNNHQAKQN
  LYDLDEDDDGIASVPTKQMKFAASGGFLHHMAGLSSSKLSMSKALPLTKVVQNDAYTAPA
  LPSSIRTKALTNMSRTLVNKEEPPKELPAAEPVLSPLEGTKMTVNNLHPRVTEEDIVELF
  CVCGALKRARLVHPGVAEVVFVKKDDAITAYKKYNNRCLDGQPMKCNLHMNGNVITSDQP
  ILLRLSDSPSMKKESELPRRVNSASSSNPPAEVDPDTILKALFKSSGASVTTQPTEFKIK
  L
• Function: Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex.
• Reactome Pathway:
  mRNA 3'-end processing (R-HSA-72187)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Disorder of glycogen metabolism	DISYGNOB	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[2]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Genetic Variation	[3]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[4]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[5]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[2]
Autosomal dominant prognathism	DIS2G3FF	moderate	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[7]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[8]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Polymerase delta-interacting protein 3 (POLDIP3) increases the response to substance of Dexamethasone.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Polymerase delta-interacting protein 3 (POLDIP3).	[17]

2 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 affects the phosphorylation of Polymerase delta-interacting protein 3 (POLDIP3).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Polymerase delta-interacting protein 3 (POLDIP3).	[15]

References

• [1] Selective Toll-Like Receptor 4 Antagonists Prevent Acute Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Mice.Mol Neurobiol. 2019 Feb;56(2):976-985. doi: 10.1007/s12035-018-1145-2. Epub 2018 May 31.
• [2] Enhanced expression of p46 Shc in the nucleus and p52 Shc in the cytoplasm of human gastric cancer.Int J Oncol. 2005 Apr;26(4):905-11.
• [3] New lessons in the regulation of glucose metabolism taught by the glucose 6-phosphatase system.Eur J Biochem. 2000 Mar;267(6):1533-49. doi: 10.1046/j.1432-1327.2000.01160.x.
• [4] The ribonuclease L-dependent antiviral roles of human 2',5'-oligoadenylate synthetase family members against hepatitis C virus.FEBS Lett. 2013 Jan 16;587(2):156-64. doi: 10.1016/j.febslet.2012.11.010. Epub 2012 Nov 26.
• [5] Anthocyanins Function as Anti-Inflammatory Agents in a Drosophila Model for Adipose Tissue Macrophage Infiltration.Biomed Res Int. 2018 Mar 12;2018:6413172. doi: 10.1155/2018/6413172. eCollection 2018.
• [6] Skeletal and dentoalveolar effects of hybrid rapid palatal expansion and facemask treatment in growing skeletal Class III patients.Am J Orthod Dentofacial Orthop. 2018 Feb;153(2):262-268. doi: 10.1016/j.ajodo.2017.06.022.
• [7] An alternative POLDIP3 transcript promotes hepatocellular carcinoma progression.Biomed Pharmacother. 2017 May;89:276-283. doi: 10.1016/j.biopha.2017.01.139. Epub 2017 Feb 24.
• [8] Alteration of POLDIP3 splicing associated with loss of function of TDP-43 in tissues affected with ALS.PLoS One. 2012;7(8):e43120. doi: 10.1371/journal.pone.0043120. Epub 2012 Aug 10.
• [9] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [10] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 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.
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL. Eur J Cancer. 2010 Jul;46(10):1848-55. doi: 10.1016/j.ejca.2010.03.026. Epub 2010 Apr 17.