Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGAOL01)

DOT Name Neuron navigator 2 (NAV2)
Synonyms EC 3.6.4.12; Helicase APC down-regulated 1; Pore membrane and/or filament-interacting-like protein 2; Retinoic acid inducible in neuroblastoma 1; Steerin-2; Unc-53 homolog 2; unc53H2
Gene Name NAV2
Related Disease
Alzheimer disease ( )
Atrial fibrillation ( )
Colorectal carcinoma ( )
Hepatitis ( )
Rheumatoid arthritis ( )
Venous thromboembolism ( )
Acute myelogenous leukaemia ( )
Familial atrial fibrillation ( )
Neuroblastoma ( )
Colon cancer ( )
Cutaneous melanoma ( )
Melanoma ( )
UniProt ID
NAV2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2YRN
EC Number
3.6.4.12
Pfam ID
PF00307
Sequence
MPAILVASKMKSGLPKPVHSAAPILHVPPARAGPQPCYLKLGSKVEVSKTTYPSQIPLKS
QVLQGLQEPAGEGLPLRKSGSVENGFDTQIYTDWANHYLAKSGHKRLIRDLQQDVTDGVL
LAQIIQVVANEKIEDINGCPKNRSQMIENIDACLNFLAAKGINIQGLSAEEIRNGNLKAI
LGLFFSLSRYKQQQQQPQKQHLSSPLPPAVSQVAGAPSQCQAGTPQQQVPVTPQAPCQPH
QPAPHQQSKAQAEMQSSASSKDSSQSKIIRFTLGQKKISRLPGPTARVSAAGSEAKTRGG
STTANNRRSQSFNNYDKSKPVTSPPPPPSSHEKEPLASSASSHPGMSDNAPASLESGSSS
TPTNCSTSSAIPQPGAATKPWRSKSLSVKHSATVSMLSVKPPGPEAPRPTPEAMKPAPNN
QKSMLEKLKLFNSKGGSKAGEGPGSRDTSCERLETLPSFEESEELEAASRMLTTVGPASS
SPKIALKGIAQRTFSRALTNKKSSLKGNEKEKEKQQREKDKEKSKDLAKRASVTERLDLK
EEPKEDPSGAAVPEMPKKSSKIASFIPKGGKLNSAKKEPMAPSHSGIPKPGMKSMPGKSP
SAPAPSKEGERSRSGKLSSGLPQQKPQLDGRHSSSSSSLASSEGKGPGGTTLNHSISSQT
VSGSVGTTQTTGSNTVSVQLPQPQQQYNHPNTATVAPFLYRSQTDTEGNVTAESSSTGVS
VEPSHFTKTGQPALEELTGEDPEARRLRTVKNIADLRQNLEETMSSLRGTQVTHSTLETT
FDTNVTTEMSGRSILSLTGRPTPLSWRLGQSSPRLQAGDAPSMGNGYPPRANASRFINTE
SGRYVYSAPLRRQLASRGSSVCHVDVSDKAGDEMDLEGISMDAPGYMSDGDVLSKNIRTD
DITSGYMTDGGLGLYTRRLNRLPDGMAVVRETLQRNTSLGLGDADSWDDSSSVSSGISDT
IDNLSTDDINTSSSISSYANTPASSRKNLDVQTDAEKHSQVERNSLWSGDDVKKSDGGSD
SGIKMEPGSKWRRNPSDVSDESDKSTSGKKNPVISQTGSWRRGMTAQVGITMPRTKPSAP
AGALKTPGTGKTDDAKVSEKGRLSPKASQVKRSPSDAGRSSGDESKKPLPSSSRTPTANA
NSFGFKKQSGSAAGLAMITASGVTVTSRSATLGKIPKSSALVSRSAGRKSSMDGAQNQDD
GYLALSSRTNLQYRSLPRPSKSNSRNGAGNRSSTSSIDSNISSKSAGLPVPKLREPSKTA
LGSSLPGLVNQTDKEKGISSDNESVASCNSVKVNPAAQPVSSPAQTSLQPGAKYPDVASP
TLRRLFGGKPTKQVPIATAENMKNSVVISNPHATMTQQGNLDSPSGSGVLSSGSSSPLYS
KNVDLNQSPLASSPSSAHSAPSNSLTWGTNASSSSAVSKDGLGFQSVSSLHTSCESIDIS
LSSGGVPSHNSSTGLIASSKDDSLTPFVRTNSVKTTLSESPLSSPAASPKFCRSTLPRKQ
DSDPHLDRNTLPKKGLRYTPTSQLRTQEDAKEWLRSHSAGGLQDTAANSPFSSGSSVTSP
SGTRFNFSQLASPTTVTQMSLSNPTMLRTHSLSNADGQYDPYTDSRFRNSSMSLDEKSRT
MSRSGSFRDGFEEESWEKSSVDNFVSRLHSSLHFSLPLFHHARYELVHGSSLSLVSSTSS
VYSTPEEKCQSEIRKLRRELDASQEKVSALTTQLTANAHLVAAFEQSLGNMTIRLQSLTM
TAEQKDSELNELRKTIELLKKQNAAAQAAINGVINTPELNCKGNGTAQSADLRIRRQHSS
DSVSSINSATSHSSVGSNIESDSKKKKRKNWVNELRSSFKQAFGKKKSPKSASSHSDIEE
MTDSSLPSSPKLPHNGSTGSTPLLRNSHSNSLISECMDSEAETVMQLRNELRDKEMKLTD
IRLEALSSAHQLDQLREAMNRMQSEIEKLKAENDRLKSESQGSGCSRAPSQVSISASPRQ
SMGLSQHSLNLTESTSLDMLLDDTGECSARKEGGRHVKIVVSFQEEMKWKEDSRPHLFLI
GCIGVSGKTKWDVLDGVVRRLFKEYIIHVDPVSQLGLNSDSVLGYSIGEIKRSNTSETPE
LLPCGYLVGENTTISVTVKGLAENSLDSLVFESLIPKPILQRYVSLLIEHRRIILSGPSG
TGKTYLANRLSEYIVLREGRELTDGVIATFNVDHKSSKELRQYLSNLADQCNSENNAVDM
PLVIILDNLHHVSSLGEIFNGLLNCKYHKCPYIIGTMNQATSSTPNLQLHHNFRWVLCAN
HTEPVKGFLGRFLRRKLMETEISGRVRNMELVKIIDWIPKVWHHLNRFLEAHSSSDVTIG
PRLFLSCPIDVDGSRVWFTDLWNYSIIPYLLEAVREGLQLYGRRAPWEDPAKWVMDTYPW
AASPQQHEWPPLLQLRPEDVGFDGYSMPREGSTSKQMPPSDAEGDPLMNMLMRLQEAANY
SSPQSYDSDSNSNSHHDDILDSSLESTL
Function Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs.
Tissue Specificity Highly expressed in the brain, kidney and liver. Also expressed in the thyroid, mammary gland, spinal cord, heart, placenta and lung. Abundantly expressed in colon cancers.

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Genetic Variation [1]
Atrial fibrillation DIS15W6U Strong Genetic Variation [2]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [3]
Hepatitis DISXXX35 Strong Genetic Variation [4]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [5]
Venous thromboembolism DISUR7CR Strong Genetic Variation [6]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [7]
Familial atrial fibrillation DISL4AGF moderate Biomarker [2]
Neuroblastoma DISVZBI4 moderate Biomarker [8]
Colon cancer DISVC52G Limited Altered Expression [9]
Cutaneous melanoma DIS3MMH9 Limited Altered Expression [10]
Melanoma DIS1RRCY Limited Posttranslational Modification [11]
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⏷ Show the Full List of 12 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 Neuron navigator 2 (NAV2). [12]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Neuron navigator 2 (NAV2). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Neuron navigator 2 (NAV2). [28]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Neuron navigator 2 (NAV2). [30]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Neuron navigator 2 (NAV2). [31]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Neuron navigator 2 (NAV2). [30]
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⏷ Show the Full List of 6 Drug(s)
18 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 Neuron navigator 2 (NAV2). [13]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Neuron navigator 2 (NAV2). [14]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Neuron navigator 2 (NAV2). [15]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Neuron navigator 2 (NAV2). [16]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Neuron navigator 2 (NAV2). [17]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Neuron navigator 2 (NAV2). [18]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Neuron navigator 2 (NAV2). [20]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Neuron navigator 2 (NAV2). [21]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Neuron navigator 2 (NAV2). [22]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Neuron navigator 2 (NAV2). [23]
Marinol DM70IK5 Approved Marinol increases the expression of Neuron navigator 2 (NAV2). [24]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Neuron navigator 2 (NAV2). [25]
Selenium DM25CGV Approved Selenium decreases the expression of Neuron navigator 2 (NAV2). [26]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Neuron navigator 2 (NAV2). [27]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Neuron navigator 2 (NAV2). [29]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Neuron navigator 2 (NAV2). [32]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Neuron navigator 2 (NAV2). [33]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE DMNQL17 Investigative 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Neuron navigator 2 (NAV2). [34]
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⏷ Show the Full List of 18 Drug(s)

References

1 Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease.J Neuroimmunol. 2017 Sep 15;310:60-65. doi: 10.1016/j.jneuroim.2017.06.010. Epub 2017 Jun 27.
2 Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
3 Neuron navigator 2 overexpression indicates poor prognosis of colorectal cancer and promotes invasion through the SSH1L/cofilin-1 pathway.J Exp Clin Cancer Res. 2015 Oct 9;34:117. doi: 10.1186/s13046-015-0237-3.
4 Genome-wide association study of hepatitis in korean populations.Genomics Inform. 2014 Dec;12(4):203-7. doi: 10.5808/GI.2014.12.4.203. Epub 2014 Dec 31.
5 Genome-wide association study of response to tumour necrosis factor inhibitor therapy in rheumatoid arthritis.Pharmacogenomics J. 2018 Sep;18(5):657-664. doi: 10.1038/s41397-018-0040-6. Epub 2018 Aug 31.
6 Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism.Blood. 2019 Nov 7;134(19):1645-1657. doi: 10.1182/blood.2019000435.
7 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.
8 A mammalian homolog of unc-53 is regulated by all-trans retinoic acid in neuroblastoma cells and embryos.Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3422-7. doi: 10.1073/pnas.052017399.
9 Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas.Oncogene. 2002 Sep 12;21(41):6387-94. doi: 10.1038/sj.onc.1205751.
10 NAV2 facilitates invasion of cutaneous melanoma cells by targeting SNAI2 through the GSK-3/-catenin pathway.Arch Dermatol Res. 2019 Jul;311(5):399-410. doi: 10.1007/s00403-019-01909-w. Epub 2019 Apr 17.
11 DNA hypermethylation is associated with invasive phenotype of malignant melanoma.Exp Dermatol. 2020 Jan;29(1):39-50. doi: 10.1111/exd.14047. Epub 2019 Nov 14.
12 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.
13 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.
14 Role of all-trans retinoic acid in neurite outgrowth and axonal elongation. J Neurobiol. 2006 Jun;66(7):739-56. doi: 10.1002/neu.20241.
15 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.
16 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
17 The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
18 Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
19 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.
20 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.
21 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.
22 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
23 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.
24 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
25 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
26 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.
27 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
28 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.
29 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
30 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.
31 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
32 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.
33 The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.
34 Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.