Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWYT1VS)

DOT Name Adenylate kinase 9 (AK9)
Synonyms AK 9; EC 2.7.4.4; EC 2.7.4.6; Adenylate kinase domain-containing protein 1; Adenylate kinase domain-containing protein 2
Gene Name AK9
Related Disease
Major depressive disorder ( )
Acute myelogenous leukaemia ( )
Postsynaptic congenital myasthenic syndrome ( )
UniProt ID
KAD9_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.4.4; 2.7.4.6
Pfam ID
PF00406
Sequence
MTSQEKTEEYPFADIFDEDETERNFLLSKPVCFVVFGKPGVGKTTLARYITQAWKCIRVE
ALPILEEQIAAETESGVMLQSMLISGQSIPDELVIKLMLEKLNSPEVCHFGYIITEIPSL
SQDAMTTLQQIELIKNLNLKPDVIINIKCPDYDLCQRISGQRQHNNTGYIYSRDQWDPEV
IENHRKKKKEAQKDGKGEEEEEEEEQEEEEAFIAEMQMVAEILHHLVQRPEDYLENVENI
VKLYKETILQTLEEVMAEHNPQYLIELNGNKPAEELFMIVMDRLKYLNLKRAAILTKLQG
AEEEINDTMENDELFRTLASYKLIAPRYRWQRSKWGRTCPVNLKDGNIYSGLPDYSVSFL
GKIYCLSSEEALKPFLLNPRPYLLPPMPGPPCKVFILGPQYSGKTTLCNMLAENYKGKVV
DYAQLVQPRFDKARETLVENTIAEATAAAIKVVKEKLLRELQARKQAETALREFQRQYEK
MEFGVFPMEATHSSIDEEGYIQGSQRDRGSSLVDTEEAKTKSENVLHDQAAKVDKDDGKE
TGETFTFKRHSQDASQDVKLYSDTAPTEDLIEEVTADHPEVVTMIEETIKMSQDINFEQP
YEKHAEILQEVLGEVMEENKDRFPGAPKYGGWIVDNCPIVKELWMALIKKGIIPDLVIYL
SDTENNGKCLFNRIYLQKKSEIDSKILERLLEELQKKKKEEEEARKATEEELRLEEENRR
LLELMKVKAKEAEETDNEDEEEIEGDELEVHEEPEASHDTRGSWLPEEFEASEVPETEPE
AVSEPIEETTVETEIPKGSKEGLEIEKLSETVVLPEFPEDSYPDVPEMEPFKEKIGSFII
LWKQLEATISEAYIKILNLEIADRTPQELLQKVVETMEKPFQYTAWELTGEDYEEETEDY
QTEAEVDEELEEEEEEEGEDKMKERKRHLGDTKHFCPVVLKENFILQPGNTEEAAKYREK
IYYFSSAEAKEKFLEHPEDYVAHEEPLKAPPLRICLVGPQGSGKTMCGRQLAEKLNIFHI
QFEEVLQEKLLLKTEKKVGPEFEEDSENEQAAKQELEELAIQANVKVEEENTKKQLPEVQ
LTEEEEVIKSSLMENEPLPPEILEVILSEWWLKEPIRSTGFILDGFPRYPEEAQFLGDRG
FFPDAAVFIQVDDQDIFDRLLPAQIEKWKLKQKKKLERKKLIKDMKAKIRVDTIAKRRAE
LILERDKKRRENVVRDDEEISEEELEEDNDDIENILEDEFPKDEEEMSGEEDEEQETDAI
ERLRGELGEKFEADTHNLQIIQDELERYLIPIISINGARRNHIVQYTLNMKLKPLVENRA
SIFEKCHPIPAPLAQKMLTFTYKYISSFGYWDPVKLSEGETIKPVENAENPIYPVIHRQY
IYFLSSKETKEKFMKNPIKYIRQPKPKPTVPIRIIIVGPPKSGKTTVAKKITSEYGLKHL
SIGGALRYVLNNHPETELALMLNWHLHKGMTAPDELAIQALELSLMESVCNTAGVVIDGY
PVTKHQMNLLEARSIIPMVIFELSVPSKEIFKRLLLEKENEQRLPYPLHNSAQIVAVNNV
KYRKNIGEIRQYYQEQHQNWYVIDGFHSKWWVWNEVIKNVQMVNKYMQTYLERIKAGKAA
CIDKLCITPQELLSRLGEFEQFCPVSLAESQELFDCSATDSLEFAAEFRGHYYKMSSQEK
LNKFLENPELYVPPLAPHPLPSADMIPKRLTLSELKSRFPKCAELQGYCPVTYKDGNQRY
EALVPGSINYALEYHNRIYICENKEKLQKFLRSPLKYWEQKLPHKLPPLREPILLTSLPL
PGYLEQGIATSLIKAMNAAGCLKPKFPFLSIRRSALLYIALHLKAFNPKGSEYTRKKYKK
KMEQFMESCELITYLGAKMTRKYKEPQFRAIDFDHKLKTFLSLRNIDPING
Function
Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Has both nucleoside monophosphate and diphosphate kinase activities. Catalyzes the phosphorylation of AMP, dAMP, CMP and dCMP with ATP as phosphate donor and of CMP with GTP as phosphate donor. Also catalyzes the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and TTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donor. Shows substrate preference of CDP > UDP > ADP > GDP > TDP.
KEGG Pathway
Purine metabolism (hsa00230 )
Pyrimidine metabolism (hsa00240 )
Metabolic pathways (hsa01100 )
Nucleotide metabolism (hsa01232 )
Biosynthesis of cofactors (hsa01240 )
Reactome Pathway
Interconversion of nucleotide di- and triphosphates (R-HSA-499943 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Major depressive disorder DIS4CL3X Strong Genetic Variation [1]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [2]
Postsynaptic congenital myasthenic syndrome DIS92VN2 Supportive Autosomal recessive [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 Adenylate kinase 9 (AK9). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Adenylate kinase 9 (AK9). [10]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Adenylate kinase 9 (AK9). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Adenylate kinase 9 (AK9). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Adenylate kinase 9 (AK9). [7]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Adenylate kinase 9 (AK9). [8]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Adenylate kinase 9 (AK9). [9]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Adenylate kinase 9 (AK9). [11]
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⏷ Show the Full List of 6 Drug(s)

References

1 GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.J Affect Disord. 2019 Jan 15;243:16-22. doi: 10.1016/j.jad.2018.09.003. Epub 2018 Sep 7.
2 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
3 Limb girdle myasthenia with digenic RAPSN and a novel disease gene AK9 mutations. Eur J Hum Genet. 2017 Feb;25(2):192-199. doi: 10.1038/ejhg.2016.162. Epub 2016 Dec 14.
4 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.
5 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.
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 Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems. Toxicol Lett. 2016 Jan 5;240(1):50-9.
8 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.
9 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
10 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.
11 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.