Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBUCUW6)

DOT Name Serine/threonine-protein kinase Nek1 (NEK1)
Synonyms EC 2.7.11.1; Never in mitosis A-related kinase 1; NimA-related protein kinase 1; Renal carcinoma antigen NY-REN-55
Gene Name NEK1
Related Disease
Amyotrophic lateral sclerosis, susceptibility to, 24 ( )
Short-rib thoracic dysplasia 6 with or without polydactyly ( )
Orofaciodigital syndrome type II ( )
Short rib-polydactyly syndrome, Majewski type ( )
UniProt ID
NEK1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
4APC; 4B9D
EC Number
2.7.11.1
Pfam ID
PF00069
Sequence
MEKYVRLQKIGEGSFGKAILVKSTEDGRQYVIKEINISRMSSKEREESRREVAVLANMKH
PNIVQYRESFEENGSLYIVMDYCEGGDLFKRINAQKGVLFQEDQILDWFVQICLALKHVH
DRKILHRDIKSQNIFLTKDGTVQLGDFGIARVLNSTVELARTCIGTPYYLSPEICENKPY
NNKSDIWALGCVLYELCTLKHAFEAGSMKNLVLKIISGSFPPVSLHYSYDLRSLVSQLFK
RNPRDRPSVNSILEKGFIAKRIEKFLSPQLIAEEFCLKTFSKFGSQPIPAKRPASGQNSI
SVMPAQKITKPAAKYGIPLAYKKYGDKKLHEKKPLQKHKQAHQTPEKRVNTGEERRKISE
EAARKRRLEFIEKEKKQKDQIISLMKAEQMKRQEKERLERINRAREQGWRNVLSAGGSGE
VKAPFLGSGGTIAPSSFSSRGQYEHYHAIFDQMQQQRAEDNEAKWKREIYGRGLPERGIL
PGVRPGFPYGAAGHHHFPDADDIRKTLKRLKAVSKQANANRQKGQLAVERAKQVEEFLQR
KREAMQNKARAEGHMVYLARLRQIRLQNFNERQQIKAKLRGEKKEANHSEGQEGSEEADM
RRKKIESLKAHANARAAVLKEQLERKRKEAYEREKKVWEEHLVAKGVKSSDVSPPLGQHE
TGGSPSKQQMRSVISVTSALKEVGVDSSLTDTRETSEEMQKTNNAISSKREILRRLNENL
KAQEDEKGKQNLSDTFEINVHEDAKEHEKEKSVSSDRKKWEAGGQLVIPLDELTLDTSFS
TTERHTVGEVIKLGPNGSPRRAWGKSPTDSVLKILGEAELQLQTELLENTTIRSEISPEG
EKYKPLITGEKKVQCISHEINPSAIVDSPVETKSPEFSEASPQMSLKLEGNLEEPDDLET
EILQEPSGTNKDESLPCTITDVWISEEKETKETQSADRITIQENEVSEDGVSSTVDQLSD
IHIEPGTNDSQHSKCDVDKSVQPEPFFHKVVHSEHLNLVPQVQSVQCSPEESFAFRSHSH
LPPKNKNKNSLLIGLSTGLFDANNPKMLRTCSLPDLSKLFRTLMDVPTVGDVRQDNLEID
EIEDENIKEGPSDSEDIVFEETDTDLQELQASMEQLLREQPGEEYSEEEESVLKNSDVEP
TANGTDVADEDDNPSSESALNEEWHSDNSDGEIASECECDSVFNHLEELRLHLEQEMGFE
KFFEVYEKIKAIHEDEDENIEICSKIVQNILGNEHQHLYAKILHLVMADGAYQEDNDE
Function
Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. Involved in DNA damage checkpoint control and for proper DNA damage repair. In response to injury that includes DNA damage, NEK1 phosphorylates VDAC1 to limit mitochondrial cell death. May be implicated in the control of meiosis. Involved in cilium assembly.
Tissue Specificity High fetal expression in the brain and kidney.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Amyotrophic lateral sclerosis, susceptibility to, 24 DISIQNXO Definitive Autosomal dominant [1]
Short-rib thoracic dysplasia 6 with or without polydactyly DISEN8P1 Definitive Autosomal recessive [2]
Orofaciodigital syndrome type II DIS4O7OQ Supportive Autosomal recessive [3]
Short rib-polydactyly syndrome, Majewski type DIS0GCAA Supportive Autosomal recessive [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Serine/threonine-protein kinase Nek1 (NEK1). [5]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [6]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [7]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [11]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [13]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [14]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [15]
Selenium DM25CGV Approved Selenium decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [16]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [17]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Serine/threonine-protein kinase Nek1 (NEK1). [18]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Nek1 (NEK1). [19]
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⏷ Show the Full List of 16 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of Serine/threonine-protein kinase Nek1 (NEK1). [20]
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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 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
3 Compound heterozygous NEK1 variants in two siblings with oral-facial-digital syndrome type II (Mohr syndrome). Eur J Hum Genet. 2016 Dec;24(12):1752-1760. doi: 10.1038/ejhg.2016.103. Epub 2016 Aug 17.
4 Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):165-74. doi: 10.1002/ajmg.c.31336. Epub 2012 Jul 12.
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 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.
7 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.
8 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
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 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.
13 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
14 Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
15 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.
16 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
17 Cellular response to 5-fluorouracil (5-FU) in 5-FU-resistant colon cancer cell lines during treatment and recovery. Mol Cancer. 2006 May 18;5:20. doi: 10.1186/1476-4598-5-20.
18 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
19 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
20 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.