Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJE1KXL)

DOT Name Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2)
Synonyms Phosphorylase kinase alpha L subunit
Gene Name PHKA2
Related Disease
Glycogen storage disease IXa1 ( )
Advanced cancer ( )
Disorder of glycogen metabolism ( )
Glycogen storage disease I ( )
Glycogen storage disease due to liver phosphorylase kinase deficiency ( )
Gerstmann-Straussler-Scheinker syndrome ( )
UniProt ID
KPB2_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
MRSRSNSGVRLDGYARLVQQTILCYQNPVTGLLSASHEQKDAWVRDNIYSILAVWGLGMA
YRKNADRDEDKAKAYELEQNVVKLMRGLLQCMMRQVAKVEKFKHTQSTKDSLHAKYNTAT
CGTVVGDDQWGHLQVDATSLFLLFLAQMTASGLRIIFTLDEVAFIQNLVFYIEAAYKVAD
YGMWERGDKTNQGIPELNASSVGMAKAALEAIDELDLFGAHGGRKSVIHVLPDEVEHCQS
ILFSMLPRASTSKEIDAGLLSIISFPAFAVEDVNLVNVTKNEIISKLQGRYGCCRFLRDG
YKTPREDPNRLHYDPAELKLFENIECEWPVFWTYFIIDGVFSGDAVQVQEYREALEGILI
RGKNGIRLVPELYAVPPNKVDEEYKNPHTVDRVPMGKVPHLWGQSLYILSSLLAEGFLAA
GEIDPLNRRFSTSVKPDVVVQVTVLAENNHIKDLLRKHGVNVQSIADIHPIQVQPGRILS
HIYAKLGRNKNMNLSGRPYRHIGVLGTSKLYVIRNQIFTFTPQFTDQHHFYLALDNEMIV
EMLRIELAYLCTCWRMTGRPTLTFPISRTMLTNDGSDIHSAVLSTIRKLEDGYFGGARVK
LGNLSEFLTTSFYTYLTFLDPDCDEKLFDNASEGTFSPDSDSDLVGYLEDTCNQESQDEL
DHYINHLLQSTSLRSYLPPLCKNTEDRHVFSAIHSTRDILSVMAKAKGLEVPFVPMTLPT
KVLSAHRKSLNLVDSPQPLLEKVPESDFQWPRDDHGDVDCEKLVEQLKDCSNLQDQADIL
YILYVIKGPSWDTNLSGQHGVTVQNLLGELYGKAGLNQEWGLIRYISGLLRKKVEVLAEA
CTDLLSHQKQLTVGLPPEPREKIISAPLPPEELTKLIYEASGQDISIAVLTQEIVVYLAM
YVRAQPSLFVEMLRLRIGLIIQVMATELARSLNCSGEEASESLMNLSPFDMKNLLHHILS
GKEFGVERSVRPIHSSTSSPTISIHEVGHTGVTKTERSGINRLRSEMKQMTRRFSADEQF
FSVGQAASSSAHSSKSARSSTPSSPTGTSSSDSGGHHIGWGERQGQWLRRRRLDGAINRV
PVGFYQRVWKILQKCHGLSIDGYVLPSSTTREMTPHEIKFAVHVESVLNRVPQPEYRQLL
VEAIMVLTLLSDTEMTSIGGIIHVDQIVQMASQLFLQDQVSIGAMDTLEKDQATGICHFF
YDSAPSGAYGTMTYLTRAVASYLQELLPNSGCQMQ
Function Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
Tissue Specificity Predominantly expressed in liver and other non-muscle tissues.
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:HS00576-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glycogen storage disease IXa1 DISNBY0U Definitive X-linked [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Disorder of glycogen metabolism DISYGNOB Strong Genetic Variation [3]
Glycogen storage disease I DISY4Q9T Strong Biomarker [4]
Glycogen storage disease due to liver phosphorylase kinase deficiency DISTTAS6 Supportive Autosomal recessive [5]
Gerstmann-Straussler-Scheinker syndrome DISIO6KC Disputed Genetic Variation [6]
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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
11 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 Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [8]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [10]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [11]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [12]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [13]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [7]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [14]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the expression of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [18]
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⏷ Show the Full List of 11 Drug(s)
3 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 alpha, liver isoform (PHKA2). [16]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [17]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Phosphorylase b kinase regulatory subunit alpha, liver isoform (PHKA2). [17]
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References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 A critical review of the role of M(2)PYK in the Warburg effect.Biochim Biophys Acta Rev Cancer. 2019 Apr;1871(2):225-239. doi: 10.1016/j.bbcan.2019.01.004. Epub 2019 Jan 29.
3 Clinical and genetic characteristics of 17 Chinese patients with glycogen storage disease type IXa.Gene. 2017 Sep 5;627:149-156. doi: 10.1016/j.gene.2017.06.026. Epub 2017 Jun 13.
4 Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type I and II. Am J Hum Genet. 1999 Jun;64(6):1541-9. doi: 10.1086/302399.
5 Clinical Practice Guidelines for Rare Diseases: The Orphanet Database. PLoS One. 2017 Jan 18;12(1):e0170365. doi: 10.1371/journal.pone.0170365. eCollection 2017.
6 Mutation in PHKA2 leading to childhood glycogen storage disease type IXa: A case report and literature review.Medicine (Baltimore). 2019 Nov;98(46):e17775. doi: 10.1097/MD.0000000000017775.
7 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.
8 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.
9 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.
10 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.
11 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
12 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.
13 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.
14 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.
15 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
16 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.
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 Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.