Details of Drug Off-Target (DOT)

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

DOT Name BTB/POZ domain-containing protein KCTD17 (KCTD17)
Gene Name KCTD17
Related Disease
Dystonia ( )
Fatty liver disease ( )
Myoclonic dystonia 11 ( )
Myoclonic dystonia 26 ( )
Non-alcoholic fatty liver disease ( )
Myoclonus-dystonia syndrome ( )
UniProt ID
KCD17_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5A6R
Pfam ID
PF02214
Sequence
MRMEAGEAAPPAGAGGRAAGGWGKWVRLNVGGTVFLTTRQTLCREQKSFLSRLCQGEELQ
SDRDETGAYLIDRDPTYFGPILNFLRHGKLVLDKDMAEEGVLEEAEFYNIGPLIRIIKDR
MEEKDYTVTQVPPKHVYRVLQCQEEELTQMVSTMSDGWRFEQLVNIGSSYNYGSEDQAEF
LCVVSKELHSTPNGLSSESSRKTKSTEEQLEEQQQQEEEVEEVEVEQVQVEADAQEKAQS
SQDPANLFSLPPLPPPPLPAGGSRPHPLRPEAELAVRASPRPLARPQSCHPCCYKPEAPG
CEAPDHLQGLGVPI
Function
Substrate-adapter for CUL3-RING ubiquitin ligase complexes which mediates the ubiquitination and subsequent proteasomal degradation of TCHP, a protein involved in ciliogenesis down-regulation. Thereby, positively regulates ciliogenesis, playing a crucial role in the initial steps of axoneme extension. May also play a role in endoplasmic reticulum calcium ion homeostasis.
Tissue Specificity Highly expressed in brain. Highest expression is observed in the putamen and the thalamus.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Dystonia DISJLFGW Strong Biomarker [1]
Fatty liver disease DIS485QZ Strong Altered Expression [2]
Myoclonic dystonia 11 DISMVAWP Strong GermlineCausalMutation [3]
Myoclonic dystonia 26 DISGQSF5 Strong Autosomal dominant [3]
Non-alcoholic fatty liver disease DISDG1NL Strong Altered Expression [2]
Myoclonus-dystonia syndrome DISYK06B Supportive Autosomal dominant [3]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of BTB/POZ domain-containing protein KCTD17 (KCTD17). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of BTB/POZ domain-containing protein KCTD17 (KCTD17). [8]
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4 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 BTB/POZ domain-containing protein KCTD17 (KCTD17). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of BTB/POZ domain-containing protein KCTD17 (KCTD17). [6]
Selenium DM25CGV Approved Selenium increases the expression of BTB/POZ domain-containing protein KCTD17 (KCTD17). [7]
KOJIC ACID DMP84CS Investigative KOJIC ACID decreases the expression of BTB/POZ domain-containing protein KCTD17 (KCTD17). [9]
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References

1 Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High-Throughput Sequencing.Mov Disord. 2016 Apr;31(4):471-7. doi: 10.1002/mds.26600. Epub 2016 Mar 17.
2 Degradation of PHLPP2 by KCTD17, via a Glucagon-Dependent Pathway, Promotes Hepatic Steatosis.Gastroenterology. 2017 Dec;153(6):1568-1580.e10. doi: 10.1053/j.gastro.2017.08.039. Epub 2017 Aug 30.
3 A missense mutation in KCTD17 causes autosomal dominant myoclonus-dystonia. Am J Hum Genet. 2015 Jun 4;96(6):938-47. doi: 10.1016/j.ajhg.2015.04.008. Epub 2015 May 14.
4 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
5 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
6 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.
7 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.
8 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.
9 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.