Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP38GVK)

DOT Name TBC domain-containing protein kinase-like protein (TBCK)
Gene Name TBCK
Related Disease
Epilepsy ( )
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 ( )
Intellectual disability ( )
Kidney cancer ( )
Renal carcinoma ( )
Lysosomal storage disease ( )
Neuronal ceroid lipofuscinosis ( )
UniProt ID
TBCK_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00069 ; PF00566 ; PF00581
Sequence
MFPLKDAEMGAFTFFASALPHDVCGSNGLPLTPNSIKILGRFQILKTITHPRLCQYVDIS
RGKHERLVVVAEHCERSLEDLLRERKPVSCSTVLCIAFEVLQGLQYMNKHGIVHRALSPH
NILLDRKGHIKLAKFGLYHMTAHGDDVDFPIGYPSYLAPEVIAQGIFKTTDHMPSKKPLP
SGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDTLIVLAEEHGCLDIIK
ELPETVIDLLNKCLTFHPSKRPTPDQLMKDKVFSEVSPLYTPFTKPASLFSSSLRCADLT
LPEDISQLCKDINNDYLAERSIEEVYYLWCLAGGDLEKELVNKEIIRSKPPICTLPNFLF
EDGESFGQGRDRSSLLDDTTVTLSLCQLRNRLKDVGGEAFYPLLEDDQSNLPHSNSNNEL
SAAATLPLIIREKDTEYQLNRIILFDRLLKAYPYKKNQIWKEARVDIPPLMRGLTWAALL
GVEGAIHAKYDAIDKDTPIPTDRQIEVDIPRCHQYDELLSSPEGHAKFRRVLKAWVVSHP
DLVYWQGLDSLCAPFLYLNFNNEALAYACMSAFIPKYLYNFFLKDNSHVIQEYLTVFSQM
IAFHDPELSNHLNEIGFIPDLYAIPWFLTMFTHVFPLHKIFHLWDTLLLGNSSFPFCIGV
AILQQLRDRLLANGFNECILLFSDLPEIDIERCVRESINLFCWTPKSATYRQHAQPPKPS
SDSSGGRSSAPYFSAECPDPPKTDLSRESIPLNDLKSEVSPRISAEDLIDLCELTVTGHF
KTPSKKTKSSKPKLLVVDIRNSEDFIRGHISGSINIPFSAAFTAEGELTQGPYTAMLQNF
KGKVIVIVGHVAKHTAEFAAHLVKMKYPRICILDGGINKIKPTGLLTIPSPQI
Function
Involved in the modulation of mTOR signaling and expression of mTOR complex components. Involved in the regulation of cell proliferation and growth. Involved in the control of actin-cytoskeleton organization.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Epilepsy DISBB28L Strong Genetic Variation [1]
Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 DISBHWAX Strong Autosomal recessive [2]
Intellectual disability DISMBNXP Strong Genetic Variation [1]
Kidney cancer DISBIPKM moderate Biomarker [3]
Renal carcinoma DISER9XT moderate Biomarker [3]
Lysosomal storage disease DIS6QM6U Limited Biomarker [4]
Neuronal ceroid lipofuscinosis DIS9A4K4 Limited Genetic Variation [4]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [6]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [12]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of TBC domain-containing protein kinase-like protein (TBCK). [13]
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⏷ Show the Full List of 7 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of TBC domain-containing protein kinase-like protein (TBCK). [8]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of TBC domain-containing protein kinase-like protein (TBCK). [11]
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References

1 Homozygous boricua TBCK mutation causes neurodegeneration and aberrant autophagy.Ann Neurol. 2018 Jan;83(1):153-165. doi: 10.1002/ana.25130.
2 Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy. Am J Hum Genet. 2016 Apr 7;98(4):772-81. doi: 10.1016/j.ajhg.2016.01.016. Epub 2016 Mar 31.
3 MiR-1208 Increases the Sensitivity to Cisplatin by Targeting TBCK in Renal Cancer Cells.Int J Mol Sci. 2019 Jul 19;20(14):3540. doi: 10.3390/ijms20143540.
4 Homozygous TBC1 domain-containing kinase (TBCK) mutation causes a novel lysosomal storage disease - a new type of neuronal ceroid lipofuscinosis (CLN15)?.Acta Neuropathol Commun. 2018 Dec 27;6(1):145. doi: 10.1186/s40478-018-0646-6.
5 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.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
10 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
11 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.
12 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.
13 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.