Details of Drug Off-Target (DOT)

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

DOT Name Alpha-protein kinase 3 (ALPK3)
Synonyms EC 2.7.11.1; Muscle alpha-protein kinase
Gene Name ALPK3
Related Disease
Hypertrophic cardiomyopathy ( )
Brugada syndrome 1 ( )
Cardiomyopathy ( )
Cardiomyopathy, familial hypertrophic 27 ( )
Dilated cardiomyopathy ( )
Stroke ( )
Wolcott-Rallison syndrome ( )
UniProt ID
ALPK3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.1
Pfam ID
PF02816 ; PF07679
Sequence
MGSRRAPSRGWGAGGRSGAGGDGEDDGPVWIPSPASRSYLLSVRPETSLSSNRLSHPSSG
RSTFCSIIAQLTEETQPLFETTLKSRSVSEDSDVRFTCIVTGYPEPEVTWYKDDTELDRY
CGLPKYEITHQGNRHTLQLYRCREEDAAIYQASAQNSKGIVSCSGVLEVGTMTEYKIHQR
WFAKLKRKAAAKLREIEQSWKHEKAVPGEVDTLRKLSPDRFQRKRRLSGAQAPGPSVPTR
EPEGGTLAAWQEGETETAQHSGLGLINSFASGEVTTNGEAAPENGEDGEHGLLTYICDAM
ELGPQRALKEESGAKKKKKDEESKQGLRKPELEKAAQSRRSSENCIPSSDEPDSCGTQGP
VGVEQVQTQPRGRAARGPGSSGTDSTRKPASAVGTPDKAQKAPGPGPGQEVYFSLKDMYL
ENTQAVRPLGEEGPQTLSVRAPGESPKGKAPLRARSEGVPGAPGQPTHSLTPQPTRPFNR
KRFAPPKPKGEATTDSKPISSLSQAPECGAQSLGKAPPQASVQVPTPPARRRHGTRDSTL
QGQAGHRTPGEVLECQTTTAPTMSASSSSDVASIGVSTSGSQGIIEPMDMETQEDGRTSA
NQRTGSKKNVQADGKIQVDGRTRGDGTQTAQRTRADRKTQVDAGTQESKRPQSDRSAQKG
MMTQGRAETQLETTQAGEKIQEDRKAQADKGTQEDRRMQGEKGMQGEKGTQSEGSAPTAM
EGQSEQEVATSLGPPSRTPKLPPTAGPRAPLNIECFVQTPEGSCFPKKPGCLPRSEEAVV
TASRNHEQTVLGPLSGNLMLPAQPPHEGSVEQVGGERCRGPQSSGPVEAKQEDSPFQCPK
EERPGGVPCMDQGGCPLAGLSQEVPTMPSLPGTGLTASPKAGPCSTPTSQHGSTATFLPS
EDQVLMSSAPTLHLGLGTPTQSHPPETMATSSEGACAQVPDVEGRTPGPRSCDPGLIDSL
KNYLLLLLKLSSTETSGAGGESQVGAATGGLVPSATLTPTVEVAGLSPRTSRRILERVEN
NHLVQSAQTLLLSPCTSRRLTGLLDREVQAGRQALAAARGSWGPGPSSLTVPAIVVDEED
PGLASEGASEGEGEVSPEGPGLLGASQESSMAGRLGEAGGQAAPGQGPSAESIAQEPSQE
EKFPGEALTGLPAATPEELALGARRKRFLPKVRAAGDGEATTPEERESPTVSPRGPRKSL
VPGSPGTPGRERRSPTQGRKASMLEVPRAEEELAAGDLGPSPKAGGLDTEVALDEGKQET
LAKPRKAKDLLKAPQVIRKIRVEQFPDASGSLKLWCQFFNILSDSVLTWAKDQRPVGEVG
RSAGDEGPAALAIVQASPVDCGVYRCTIHNEHGSASTDFCLSPEVLSGFISREEGEVGEE
IEMTPMVFAKGLADSGCWGDKLFGRLVSEELRGGGYGCGLRKASQAKVIYGLEPIFESGR
TCIIKVSSLLVFGPSSETSLVGRNYDVTIQGCKIQNMSREYCKIFAAEARAAPGFGEVPE
IIPLYLIYRPANNIPYATLEEDLGKPLESYCSREWGCAEAPTASGSSEAMQKCQTFQHWL
YQWTNGSFLVTDLAGVDWKMTDVQIATKLRGYQGLKESCFPALLDRFASSHQCNAYCELL
GLTPLKGPEAAHPQAKAKGSKSPSAGRKGSQLSPQPQKKGLPSPQGTRKSAPSSKATPQA
SEPVTTQLLGQPPTQEEGSKAQGMR
Function Involved in cardiomyocyte differentiation.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hypertrophic cardiomyopathy DISQG2AI Definitive Autosomal recessive [1]
Brugada syndrome 1 DISKBA7V Strong Autosomal dominant [2]
Cardiomyopathy DISUPZRG Strong Genetic Variation [3]
Cardiomyopathy, familial hypertrophic 27 DISA8NB0 Strong Autosomal dominant [4]
Dilated cardiomyopathy DISX608J Strong Biomarker [4]
Stroke DISX6UHX Strong Biomarker [5]
Wolcott-Rallison syndrome DISKVKXN Strong Genetic Variation [6]
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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
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Gemcitabine DMSE3I7 Approved Alpha-protein kinase 3 (ALPK3) increases the Neutropenia ADR of Gemcitabine. [19]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Alpha-protein kinase 3 (ALPK3). [7]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Alpha-protein kinase 3 (ALPK3). [8]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Alpha-protein kinase 3 (ALPK3). [9]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Alpha-protein kinase 3 (ALPK3). [10]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Alpha-protein kinase 3 (ALPK3). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Alpha-protein kinase 3 (ALPK3). [13]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Alpha-protein kinase 3 (ALPK3). [14]
Testosterone DM7HUNW Approved Testosterone increases the expression of Alpha-protein kinase 3 (ALPK3). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Alpha-protein kinase 3 (ALPK3). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Alpha-protein kinase 3 (ALPK3). [17]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Alpha-protein kinase 3 (ALPK3). [18]
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⏷ Show the Full List of 11 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 Alpha-protein kinase 3 (ALPK3). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Alpha-protein kinase 3 (ALPK3). [16]
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References

1 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.
2 Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy. Eur Heart J. 2021 Aug 21;42(32):3063-3073. doi: 10.1093/eurheartj/ehab424.
3 Phenotypic spectrum of ALPK3-related cardiomyopathy.Am J Med Genet A. 2019 Jul;179(7):1235-1240. doi: 10.1002/ajmg.a.61176. Epub 2019 May 10.
4 Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy. J Am Coll Cardiol. 2016 Feb 9;67(5):515-25. doi: 10.1016/j.jacc.2015.10.093.
5 Cardiomyopathy in -kinase 3 (ALPK3)-deficient mice. Vet Pathol. 2012 Jan;49(1):131-41. doi: 10.1177/0300985811402841. Epub 2011 Mar 25.
6 Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome.J Pediatr Endocrinol Metab. 2014 Sep;27(9-10):967-70. doi: 10.1515/jpem-2013-0469.
7 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
8 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.
9 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
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 Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
12 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.
13 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
14 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.
15 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
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 Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
18 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
19 Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.