Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKWD5FY)

DOT Name Serine/threonine-protein kinase Nek3 (NEK3)
Synonyms EC 2.7.11.1; HSPK 36; Never in mitosis A-related kinase 3; NimA-related protein kinase 3
Gene Name NEK3
Related Disease
Advanced cancer ( )
Gastric cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Stomach cancer ( )
Breast cancer ( )
Breast carcinoma ( )
UniProt ID
NEK3_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
PF00069
Sequence
MDDYMVLRMIGEGSFGRALLVQHESSNQMFAMKEIRLPKSFSNTQNSRKEAVLLAKMKHP
NIVAFKESFEAEGHLYIVMEYCDGGDLMQKIKQQKGKLFPEDMILNWFTQMCLGVNHIHK
KRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLSNPMAFACTYVGTPYYVPPEIWENLPYN
NKSDIWSLGCILYELCTLKHPFQANSWKNLILKVCQGCISPLPSHYSYELQFLVKQMFKR
NPSHRPSATTLLSRGIVARLVQKCLPPEIIMEYGEEVLEEIKNSKHNTPRKKTNPSRIRI
ALGNEASTVQEEEQDRKGSHTDLESINENLVESALRRVNREEKGNKSVHLRKASSPNLHR
RQWEKNVPNTALTALENASILTSSLTAEDDRGGSVIKYSKNTTRKQWLKETPDTLLNILK
NADLSLAFQTYTIYRPGSEGFLKGPLSEETEASDSVDGGHDSVILDPERLEPGLDEEDTD
FEEEDDNPDWVSELKKRAGWQGLCDR
Function
Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2.
Tissue Specificity Up-regulated in malignant versus normal breast tissue. Isoform 2 shows a high level of expression in testis, ovary and brain.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Gastric cancer DISXGOUK Strong Altered Expression [1]
Prostate cancer DISF190Y Strong Biomarker [2]
Prostate carcinoma DISMJPLE Strong Biomarker [2]
Stomach cancer DISKIJSX Strong Altered Expression [1]
Breast cancer DIS7DPX1 moderate Altered Expression [3]
Breast carcinoma DIS2UE88 moderate Altered Expression [3]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Serine/threonine-protein kinase Nek3 (NEK3). [4]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Serine/threonine-protein kinase Nek3 (NEK3). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Serine/threonine-protein kinase Nek3 (NEK3). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serine/threonine-protein kinase Nek3 (NEK3). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate affects the expression of Serine/threonine-protein kinase Nek3 (NEK3). [8]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Serine/threonine-protein kinase Nek3 (NEK3). [9]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Serine/threonine-protein kinase Nek3 (NEK3). [11]
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⏷ Show the Full List of 7 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 affects the phosphorylation of Serine/threonine-protein kinase Nek3 (NEK3). [10]
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References

1 Overexpression of NEK3 is associated with poor prognosis in patients with gastric cancer.Medicine (Baltimore). 2018 Jan;97(3):e9630. doi: 10.1097/MD.0000000000009630.
2 Is there any association between nek3 and cancers with frequent 13q14 deletion?.Cancer Invest. 2006 Nov;24(7):682-8. doi: 10.1080/07357900600981364.
3 T cell recognition of novel shared breast cancer antigens is frequently observed in peripheral blood of breast cancer patients.Oncoimmunology. 2019 Sep 30;8(12):e1663107. doi: 10.1080/2162402X.2019.1663107. eCollection 2019.
4 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
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 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.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
10 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.
11 Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.