Details of Drug Off-Target (DOT)

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

DOT Name Phosphorylase b kinase regulatory subunit beta (PHKB)
Synonyms Phosphorylase kinase subunit beta
Gene Name PHKB
Related Disease
Carcinoma of liver and intrahepatic biliary tract ( )
Glycogen storage disease IXb ( )
Liver cancer ( )
Colorectal carcinoma ( )
Disorder of glycogen metabolism ( )
UniProt ID
KPBB_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00723 ; PF19292
Sequence
MAGAAGLTAEVSWKVLERRARTKRSGSVYEPLKSINLPRPDNETLWDKLDHYYRIVKSTL
LLYQSPTTGLFPTKTCGGDQKAKIQDSLYCAAGAWALALAYRRIDDDKGRTHELEHSAIK
CMRGILYCYMRQADKVQQFKQDPRPTTCLHSVFNVHTGDELLSYEEYGHLQINAVSLYLL
YLVEMISSGLQIIYNTDEVSFIQNLVFCVERVYRVPDFGVWERGSKYNNGSTELHSSSVG
LAKAALEAINGFNLFGNQGCSWSVIFVDLDAHNRNRQTLCSLLPRESRSHNTDAALLPCI
SYPAFALDDEVLFSQTLDKVVRKLKGKYGFKRFLRDGYRTSLEDPNRCYYKPAEIKLFDG
IECEFPIFFLYMMIDGVFRGNPKQVQEYQDLLTPVLHHTTEGYPVVPKYYYVPADFVEYE
KNNPGSQKRFPSNCGRDGKLFLWGQALYIIAKLLADELISPKDIDPVQRYVPLKDQRNVS
MRFSNQGPLENDLVVHVALIAESQRLQVFLNTYGIQTQTPQQVEPIQIWPQQELVKAYLQ
LGINEKLGLSGRPDRPIGCLGTSKIYRILGKTVVCYPIIFDLSDFYMSQDVFLLIDDIKN
ALQFIKQYWKMHGRPLFLVLIREDNIRGSRFNPILDMLAALKKGIIGGVKVHVDRLQTLI
SGAVVEQLDFLRISDTEELPEFKSFEELEPPKHSKVKRQSSTPSAPELGQQPDVNISEWK
DKPTHEILQKLNDCSCLASQAILLGILLKREGPNFITKEGTVSDHIERVYRRAGSQKLWL
AVRYGAAFTQKFSSSIAPHITTFLVHGKQVTLGAFGHEEEVISNPLSPRVIQNIIYYKCN
THDEREAVIQQELVIHIGWIISNNPELFSGMLKIRIGWIIHAMEYELQIRGGDKPALDLY
QLSPSEVKQLLLDILQPQQNGRCWLNRRQIDGSLNRTPTGFYDRVWQILERTPNGIIVAG
KHLPQQPTLSDMTMYEMNFSLLVEDTLGNIDQPQYRQIVVELLMVVSIVLERNPELEFQD
KVDLDRLVKEAFNEFQKDQSRLKEIEKQDDMTSFYNTPPLGKRGTCSYLTKAVMNLLLEG
EVKPNNDDPCLIS
Function
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
Insulin sig.ling pathway (hsa04910 )
Glucagon sig.ling pathway (hsa04922 )
Reactome Pathway
Glycogen breakdown (glycogenolysis) (R-HSA-70221 )
BioCyc Pathway
MetaCyc:HS02424-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Definitive Biomarker [1]
Glycogen storage disease IXb DISXSG96 Definitive Autosomal recessive [2]
Liver cancer DISDE4BI Definitive Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [3]
Disorder of glycogen metabolism DISYGNOB Strong Biomarker [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [6]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [8]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [11]
Vorinostat DMWMPD4 Approved Vorinostat affects the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [12]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [13]
Bortezomib DMNO38U Approved Bortezomib increases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [14]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [16]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Phosphorylase b kinase regulatory subunit beta (PHKB). [18]
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⏷ Show the Full List of 12 Drug(s)
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 affects the methylation of Phosphorylase b kinase regulatory subunit beta (PHKB). [15]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Phosphorylase b kinase regulatory subunit beta (PHKB). [17]
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References

1 Phosphorylase Kinase Represents a Novel Prognostic Biomarker and Inhibits Malignant Phenotypes of Liver Cancer Cell.Int J Biol Sci. 2019 Sep 7;15(12):2596-2606. doi: 10.7150/ijbs.33278. eCollection 2019.
2 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
3 Phosphorylase kinase affects colorectal cancer cell growth and represents a novel prognostic biomarker.J Cancer Res Clin Oncol. 2017 Jun;143(6):971-980. doi: 10.1007/s00432-017-2362-1. Epub 2017 Mar 8.
4 Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.Brain. 2016 Nov 1;139(11):2844-2854. doi: 10.1093/brain/aww221.
5 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
6 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
7 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.
8 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.
9 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
10 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.
11 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.
12 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.
13 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
14 The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
15 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
16 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.
17 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.
18 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.