Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT667KTL)

DOT Name Neuron navigator 1 (NAV1)
Synonyms Pore membrane and/or filament-interacting-like protein 3; Steerin-1; Unc-53 homolog 1; unc53H1
Gene Name NAV1
Related Disease
Breast cancer ( )
Breast carcinoma ( )
Cardiovascular disease ( )
Schizophrenia ( )
Neuroblastoma ( )
UniProt ID
NAV1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLGSSVKSVQPEVELSSGGGDEGADEPRGAGRKAAAADGRGMLPKRAKAPGGGGGMAKAS
AAELKVFKSGSVDSRVPGGPPASNLRKQKSLTNLSFLTDSEKKLQLYEPEWSDDMAKAPK
GLGKVGSKGREAPLMSKTLSKSEHSLFQAKGSPAGGAKTPLAPLAPNLGKPSRIPRGPYA
EVKPLSKAPEAAVSEDGKSDDELLSSKAKAQKSSGPVPSAKGQEERAFLKVDPELVVTVL
GDLEQLLFSQMLDPESQRKRTVQNVLDLRQNLEETMSSLRGSQVTHSSLEMTCYDSDDAN
PRSVSSLSNRSSPLSWRYGQSSPRLQAGDAPSVGGSCRSEGTPAWYMHGERAHYSHTMPM
RSPSKLSHISRLELVESLDSDEVDLKSGYMSDSDLMGKTMTEDDDITTGWDESSSISSGL
SDASDNLSSEEFNASSSLNSLPSTPTASRRNSTIVLRTDSEKRSLAESGLSWFSESEEKA
PKKLEYDSGSLKMEPGTSKWRRERPESCDDSSKGGELKKPISLGHPGSLKKGKTPPVAVT
SPITHTAQSALKVAGKPEGKATDKGKLAVKNTGLQRSSSDAGRDRLSDAKKPPSGIARPS
TSGSFGYKKPPPATGTATVMQTGGSATLSKIQKSSGIPVKPVNGRKTSLDVSNSAEPGFL
APGARSNIQYRSLPRPAKSSSMSVTGGRGGPRPVSSSIDPSLLSTKQGGLTPSRLKEPTK
VASGRTTPAPVNQTDREKEKAKAKAVALDSDNISLKSIGSPESTPKNQASHPTATKLAEL
PPTPLRATAKSFVKPPSLANLDKVNSNSLDLPSSSDTTHASKVPDLHATSSASGGPLPSC
FTPSPAPILNINSASFSQGLELMSGFSVPKETRMYPKLSGLHRSMESLQMPMSLPSAFPS
STPVPTPPAPPAAPTEEETEELTWSGSPRAGQLDSNQRDRNTLPKKGLRYQLQSQEETKE
RRHSHTIGGLPESDDQSELPSPPALPMSLSAKGQLTNIVSPTAATTPRITRSNSIPTHEA
AFELYSGSQMGSTLSLAERPKGMIRSGSFRDPTDDVHGSVLSLASSASSTYSSAEERMQS
EQIRKLRRELESSQEKVATLTSQLSANANLVAAFEQSLVNMTSRLRHLAETAEEKDTELL
DLRETIDFLKKKNSEAQAVIQGALNASETTPKELRIKRQNSSDSISSLNSITSHSSIGSS
KDADAKKKKKKSWVYELRSSFNKAFSIKKGPKSASSYSDIEEIATPDSSAPSSPKLQHGS
TETASPSIKSSTSSSVGTDVTEGPAHPAPHTRLFHANEEEEPEKKEVSELRSELWEKEMK
LTDIRLEALNSAHQLDQLRETMHNMQLEVDLLKAENDRLKVAPGPSSGSTPGQVPGSSAL
SSPRRSLGLALTHSFGPSLADTDLSPMDGISTCGPKEEVTLRVVVRMPPQHIIKGDLKQQ
EFFLGCSKVSGKVDWKMLDEAVFQVFKDYISKMDPASTLGLSTESIHGYSISHVKRVLDA
EPPEMPPCRRGVNNISVSLKGLKEKCVDSLVFETLIPKPMMQHYISLLLKHRRLVLSGPS
GTGKTYLTNRLAEYLVERSGREVTEGIVSTFNMHQQSCKDLQLYLSNLANQIDRETGIGD
VPLVILLDDLSEAGSISELVNGALTCKYHKCPYIIGTTNQPVKMTPNHGLHLSFRMLTFS
NNVEPANGFLVRYLRRKLVESDSDINANKEELLRVLDWVPKLWYHLHTFLEKHSTSDFLI
GPCFFLSCPIGIEDFRTWFIDLWNNSIIPYLQEGAKDGIKVHGQKAAWEDPVEWVRDTLP
WPSAQQDQSKLYHLPPPTVGPHSIASPPEDRTVKDSTPSSLDSDPLMAMLLKLQEAANYI
ESPDRETILDPNLQATL
Function May be involved in neuronal migration.
Tissue Specificity Broadly expressed at low levels. Expressed at high levels in heart, skeletal muscle and placenta.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Strong Biomarker [1]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [2]
Schizophrenia DISSRV2N Strong Biomarker [3]
Neuroblastoma DISVZBI4 Limited Altered Expression [4]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
21 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 Neuron navigator 1 (NAV1). [5]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Neuron navigator 1 (NAV1). [6]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Neuron navigator 1 (NAV1). [7]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Neuron navigator 1 (NAV1). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Neuron navigator 1 (NAV1). [9]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Neuron navigator 1 (NAV1). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Neuron navigator 1 (NAV1). [11]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of Neuron navigator 1 (NAV1). [12]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Neuron navigator 1 (NAV1). [13]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Neuron navigator 1 (NAV1). [14]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Neuron navigator 1 (NAV1). [12]
Dexamethasone DMMWZET Approved Dexamethasone decreases the expression of Neuron navigator 1 (NAV1). [15]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Neuron navigator 1 (NAV1). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Neuron navigator 1 (NAV1). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Neuron navigator 1 (NAV1). [17]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Neuron navigator 1 (NAV1). [18]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Neuron navigator 1 (NAV1). [19]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Neuron navigator 1 (NAV1). [21]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Neuron navigator 1 (NAV1). [22]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone decreases the expression of Neuron navigator 1 (NAV1). [23]
Forskolin DM6ITNG Investigative Forskolin decreases the expression of Neuron navigator 1 (NAV1). [23]
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⏷ Show the Full List of 21 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Neuron navigator 1 (NAV1). [20]
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References

1 Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer.Hum Mol Genet. 2010 Nov 1;19(21):4273-7. doi: 10.1093/hmg/ddq351. Epub 2010 Aug 19.
2 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
3 Lack of change in markers of presynaptic terminal abundance alongside subtle reductions in markers of presynaptic terminal plasticity in prefrontal cortex of schizophrenia patients.Biol Psychiatry. 2011 Jan 1;69(1):71-9. doi: 10.1016/j.biopsych.2010.09.036.
4 Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression.Oncotarget. 2016 Apr 19;7(16):21840-52. doi: 10.18632/oncotarget.8187.
5 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
6 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
7 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
8 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.
9 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.
10 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.
11 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
12 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
13 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
14 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
15 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
16 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
17 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
18 BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
19 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
20 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.
21 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.
22 Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
23 Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.