Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4QNL67)

• DOT Name: IQ domain-containing protein K (IQCK)
• Gene Name: IQCK
• Related Disease:
  Familial Alzheimer disease
  Obesity
  Alzheimer disease
• UniProt ID: IQCK_HUMAN
• Sequence:
  MAAPRQIPSHIVRLKPSCSTDSSFTRTPVPTVSLASRELPVSSWQVTEPSSKNLWEQICK
  EYEAEQPPFPEGYKVKQEPVITVAPVEEMLFHGFSAEHYFPVSHFTMISRTPCPQDKSET
  INPKTCSPKEYLETFIFPVLLPGMASLLHQAKKEKCFERKRTKFIACDFLTEWLYNQNPK
  RAGEPFTEFFSIPFVEERLKQHPRPPIPLSLLLTEEEAALYIQSFWRACVVRCDPEIQEL
  RQWQKKLREAKHIHQQVKIFWAKQEQKVKCKMEDDAVPAAKMKIPSS

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Limited	Biomarker	[1]

14 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 IQ domain-containing protein K (IQCK).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of IQ domain-containing protein K (IQCK).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of IQ domain-containing protein K (IQCK).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of IQ domain-containing protein K (IQCK).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of IQ domain-containing protein K (IQCK).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of IQ domain-containing protein K (IQCK).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of IQ domain-containing protein K (IQCK).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of IQ domain-containing protein K (IQCK).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of IQ domain-containing protein K (IQCK).	[11]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of IQ domain-containing protein K (IQCK).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of IQ domain-containing protein K (IQCK).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of IQ domain-containing protein K (IQCK).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of IQ domain-containing protein K (IQCK).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of IQ domain-containing protein K (IQCK).	[17]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of IQ domain-containing protein K (IQCK).	[13]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of IQ domain-containing protein K (IQCK).	[14]

References

• [1] Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A, tau, immunity and lipid processing.Nat Genet. 2019 Mar;51(3):414-430. doi: 10.1038/s41588-019-0358-2. Epub 2019 Feb 28.
• [2] Genetic variation at the CELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity.Am J Med Genet B Neuropsychiatr Genet. 2014 Jun;165B(4):283-93. doi: 10.1002/ajmg.b.32234. Epub 2014 May 1.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [14] 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.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.