Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWSSXX0)

• DOT Name: Protein Red (IK)
• Synonyms: Cytokine IK; IK factor; Protein RER
• Gene Name: IK
• Related Disease:
  Arthritis
  Fatty liver disease
  Prostate cancer
  Crouzon syndrome
  Eating disorder
  Hepatitis E virus infection
  Dental caries
  Neoplasm
  Neuralgic amyotrophy
  Non-insulin dependent diabetes
• UniProt ID: RED_HUMAN
• PDB ID: 5O9Z; 6Q8I
• Pfam ID: PF07807 ; PF07808
• Sequence:
  MPERDSEPFSNPLAPDGHDVDDPHSFHQSKLTNEDFRKLLMTPRAAPTSAPPSKSRHHEM
  PREYNEDEDPAARRRKKKSYYAKLRQQEIERERELAEKYRDRAKERRDGVNKDYEETELI
  STTANYRAVGPTAEADKSAAEKRRQLIQESKFLGGDMEHTHLVKGLDFALLQKVRAEIAS
  KEKEEEELMEKPQKETKKDEDPENKIEFKTRLGRNVYRMLFKSKAYERNELFLPGRMAYV
  VDLDDEYADTDIPTTLIRSKADCPTMEAQTTLTTNDIVISKLTQILSYLRQGTRNKKLKK
  KDKGKLEEKKPPEADMNIFEDIGDYVPSTTKTPRDKERERYRERERDRERDRDRDRERER
  ERDRERERERDREREEEKKRHSYFEKPKVDDEPMDVDKGPGSTKELIKSINEKFAGSAGW
  EGTESLKKPEDKKQLGDFFGMSNSYAECYPATMDDMAVDSDEEVDYSKMDQGNKKGPLGR
  WDFDTQEEYSEYMNNKEALPKAAFQYGIKMSEGRKTRRFKETNDKAELDRQWKKISAIIE
  KRKKMEADGVEVKRPKY
• Function: Involved in pre-mRNA splicing as a component of the spliceosome. Auxiliary spliceosomal protein that regulates selection of alternative splice sites in a small set of target pre-mRNA species (Probable). Required for normal mitotic cell cycle progression. Recruits MAD1L1 and MAD2L1 to kinetochores, and is required to trigger the spindle assembly checkpoint. Required for normal accumulation of SMU1 ; (Microbial infection) Required, together with SMU1, for normal splicing of influenza A virus NS1 pre-mRNA, which is required for the production of the exportin NS2 and for the production of influenza A virus particles. Not required for the production of VSV virus particles.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[3]
Crouzon syndrome	DISIAVZU	moderate	Genetic Variation	[4]
Eating disorder	DISVGXN0	moderate	Biomarker	[5]
Hepatitis E virus infection	DIS0TXIR	Disputed	Biomarker	[6]
Dental caries	DISRBCMD	Limited	Biomarker	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
Neuralgic amyotrophy	DISYRI69	Limited	Biomarker	[9]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein Red (IK).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein Red (IK).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein Red (IK).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein Red (IK).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein Red (IK).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein Red (IK).	[16]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein Red (IK).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Protein Red (IK).	[18]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein Red (IK).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein Red (IK).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein Red (IK).	[21]

1 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 increases the sumoylation of Protein Red (IK).	[20]

References

• [1] Recombinant Adeno-Associated Virus Expressing Truncated IK Cytokine Diminishes the Symptoms of Inflammatory Arthritis.J Microbiol Biotechnol. 2017 Oct 28;27(10):1892-1895. doi: 10.4014/jmb.1705.05018.
• [2] Purple corn extract induces long-lasting reprogramming and M2 phenotypic switch of adipose tissue macrophages in obese mice.J Transl Med. 2019 Jul 23;17(1):237. doi: 10.1186/s12967-019-1972-6.
• [3] A genome-wide association study of prostate cancer in West African men.Hum Genet. 2014 May;133(5):509-21. doi: 10.1007/s00439-013-1387-z. Epub 2013 Nov 2.
• [4] Midface correction in patients with Crouzon syndrome is Le Fort III distraction osteogenesis with a rigid external distraction device the gold standard?.J Craniomaxillofac Surg. 2019 Mar;47(3):420-430. doi: 10.1016/j.jcms.2018.11.028. Epub 2018 Dec 31.
• [5] Eating Disorders in Athletes: From Risk Management to Therapy.Endocr Metab Immune Disord Drug Targets. 2020;20(1):2-14. doi: 10.2174/1871530319666190418121446.
• [6] Presence of Hepatitis E Virus in a RED Deer (Cervus elaphus) Population in Central Italy.Transbound Emerg Dis. 2017 Feb;64(1):137-143. doi: 10.1111/tbed.12353. Epub 2015 Apr 19.
• [7] Inhibition of Streptococcus mutans Biofilms by the Natural Stilbene Piceatannol Through the Inhibition of Glucosyltransferases.ACS Omega. 2018 Jul 31;3(7):8378-8385. doi: 10.1021/acsomega.8b00367. Epub 2018 Jul 30.
• [8] Engineered mesenchymal stem cells as vectors in a suicide gene therapy against preclinical murine models for solid tumors.J Control Release. 2016 Oct 10;239:82-91. doi: 10.1016/j.jconrel.2016.08.019. Epub 2016 Aug 23.
• [9] Focused high-resolution sonography of the suprascapular nerve: A simple surrogate marker for neuralgic amyotrophy?.Clin Neurophysiol. 2017 Aug;128(8):1438-1444. doi: 10.1016/j.clinph.2017.04.030. Epub 2017 May 19.
• [10] Improving Assessment of the Spectrum of Reward-Related Eating: The RED-13.Front Psychol. 2017 May 30;8:795. doi: 10.3389/fpsyg.2017.00795. eCollection 2017.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [15] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [16] 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.
• [17] 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.
• [18] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] 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.
• [21] 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.