Details of Drug Off-Target (DOT)

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

DOT Name Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1)
Synonyms Phosphorylase kinase alpha M subunit
Gene Name PHKA1
Related Disease
Disorder of glycogen metabolism ( )
Glycogen storage disease IXd ( )
Hypothyroidism ( )
Myopathy ( )
UniProt ID
KPB1_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
MRSRSNSGVRLDGYARLVQQTILCHQNPVTGLLPASYDQKDAWVRDNVYSILAVWGLGLA
YRKNADRDEDKAKAYELEQSVVKLMRGLLHCMIRQVDKVESFKYSQSTKDSLHAKYNTKT
CATVVGDDQWGHLQLDATSVYLLFLAQMTASGLHIIHSLDEVNFIQNLVFYIEAAYKTAD
FGIWERGDKTNQGISELNASSVGMAKAALEALDELDLFGVKGGPQSVIHVLADEVQHCQS
ILNSLLPRASTSKEVDASLLSVVSFPAFAVEDSQLVELTKQEIITKLQGRYGCCRFLRDG
YKTPKEDPNRLYYEPAELKLFENIECEWPLFWTYFILDGVFSGNAEQVQEYKEALEAVLI
KGKNGVPLLPELYSVPPDRVDEEYQNPHTVDRVPMGKLPHMWGQSLYILGSLMAEGFLAP
GEIDPLNRRFSTVPKPDVVVQVSILAETEEIKTILKDKGIYVETIAEVYPIRVQPARILS
HIYSSLGCNNRMKLSGRPYRHMGVLGTSKLYDIRKTIFTFTPQFIDQQQFYLALDNKMIV
EMLRTDLSYLCSRWRMTGQPTITFPISHSMLDEDGTSLNSSILAALRKMQDGYFGGARVQ
TGKLSEFLTTSCCTHLSFMDPGPEGKLYSEDYDDNYDYLESGNWMNDYDSTSHARCGDEV
ARYLDHLLAHTAPHPKLAPTSQKGGLDRFQAAVQTTCDLMSLVTKAKELHVQNVHMYLPT
KLFQASRPSFNLLDSPHPRQENQVPSVRVEIHLPRDQSGEVDFKALVLQLKETSSLQEQA
DILYMLYTMKGPDWNTELYNERSATVRELLTELYGKVGEIRHWGLIRYISGILRKKVEAL
DEACTDLLSHQKHLTVGLPPEPREKTISAPLPYEALTQLIDEASEGDMSISILTQEIMVY
LAMYMRTQPGLFAEMFRLRIGLIIQVMATELAHSLRCSAEEATEGLMNLSPSAMKNLLHH
ILSGKEFGVERSVRPTDSNVSPAISIHEIGAVGATKTERTGIMQLKSEIKQVEFRRLSIS
AESQSPGTSMTPSSGSFPSAYDQQSSKDSRQGQWQRRRRLDGALNRVPVGFYQKVWKVLQ
KCHGLSVEGFVLPSSTTREMTPGEIKFSVHVESVLNRVPQPEYRQLLVEAILVLTMLADI
EIHSIGSIIAVEKIVHIANDLFLQEQKTLGADDTMLAKDPASGICTLLYDSAPSGRFGTM
TYLSKAAATYVQEFLPHSICAMQ
Function Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
Tissue Specificity Muscle specific. Isoform 1 is predominant in vastus lateralis muscle. Isoform 2 predominates slightly in heart, and it predominates clearly in the other tissues tested.
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:HS00901-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Disorder of glycogen metabolism DISYGNOB Strong Genetic Variation [1]
Glycogen storage disease IXd DISJOJP9 Strong X-linked [2]
Hypothyroidism DISR0H6D Strong Biomarker [3]
Myopathy DISOWG27 Strong Genetic Variation [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [11]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [12]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [6]
Acetaminophen DMUIE76 Approved Acetaminophen affects the expression of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [8]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [9]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [10]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform (PHKA1). [13]
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⏷ Show the Full List of 6 Drug(s)

References

1 Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three cases and review of literature.Eur J Pediatr. 2014 May;173(5):647-53. doi: 10.1007/s00431-013-2223-0. Epub 2013 Dec 11.
2 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
3 Phosphorylase a formation in protein-glycogen particles isolated from fast-twitch muscle of euthyroid and hypothyroid rats.Arch Biochem Biophys. 1989 Oct;274(1):120-9. doi: 10.1016/0003-9861(89)90422-0.
4 Myopathy and phosphorylase kinase deficiency caused by a mutation in the PHKA1 gene. Am J Med Genet A. 2005 Feb 15;133A(1):82-4. doi: 10.1002/ajmg.a.30517.
5 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.
6 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
7 Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
10 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
11 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.
12 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.
13 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.