Details of Drug Off-Target (DOT)

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

DOT Name Serine/threonine-protein kinase Nek11 (NEK11)
Synonyms EC 2.7.11.1; Never in mitosis A-related kinase 11; NimA-related protein kinase 11
Gene Name NEK11
Related Disease
Advanced cancer ( )
Epithelial ovarian cancer ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Colorectal carcinoma ( )
UniProt ID
NEK11_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
MLKFQEAAKCVSGSTAISTYPKTLIARRYVLQQKLGSGSFGTVYLVSDKKAKRGEELKVL
KEISVGELNPNETVQANLEAQLLSKLDHPAIVKFHASFVEQDNFCIITEYCEGRDLDDKI
QEYKQAGKIFPENQIIEWFIQLLLGVDYMHERRILHRDLKSKNVFLKNNLLKIGDFGVSR
LLMGSCDLATTLTGTPHYMSPEALKHQGYDTKSDIWSLACILYEMCCMNHAFAGSNFLSI
VLKIVEGDTPSLPERYPKELNAIMESMLNKNPSLRPSAIEILKIPYLDEQLQNLMCRYSE
MTLEDKNLDCQKEAAHIINAMQKRIHLQTLRALSEVQKMTPRERMRLRKLQAADEKARKL
KKIVEEKYEENSKRMQELRSRNFQQLSVDVLHEKTHLKGMEEKEEQPEGRLSCSPQDEDE
ERWQGREEESDEPTLENLPESQPIPSMDLHELESIVEDATSDLGYHEIPEDPLVAEEYYA
DAFDSYCEESDEEEEEIALERPEKEIRNEGSQPAYRTNQQDSDIEALARCLENVLGCTSL
DTKTITTMAEDMSPGPPIFNSVMARTKMKRMRESAMQKLGTEVFEEVYNYLKRARHQNAS
EAEIRECLEKVVPQASDCFEVDQLLYFEEQLLITMGKEPTLQNHL
Function
Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation.
Tissue Specificity Poorly expressed in cerebellum, trachea, lung, appendix, and uterus.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Definitive Biomarker [1]
Epithelial ovarian cancer DIS56MH2 Definitive Biomarker [1]
Ovarian cancer DISZJHAP Definitive Biomarker [1]
Ovarian neoplasm DISEAFTY Definitive Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [2]
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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 Serine/threonine-protein kinase Nek11 (NEK11). [3]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the methylation of Serine/threonine-protein kinase Nek11 (NEK11). [7]
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5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase Nek11 (NEK11). [4]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Serine/threonine-protein kinase Nek11 (NEK11). [5]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Serine/threonine-protein kinase Nek11 (NEK11). [6]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Serine/threonine-protein kinase Nek11 (NEK11). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Nek11 (NEK11). [9]
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References

1 Downregulation of NEK11 is associated with drug resistance in ovarian cancer.Int J Oncol. 2014 Sep;45(3):1266-74. doi: 10.3892/ijo.2014.2503. Epub 2014 Jun 18.
2 Loss of Nek11 Prevents G2/M Arrest and Promotes Cell Death in HCT116 Colorectal Cancer Cells Exposed to Therapeutic DNA Damaging Agents.PLoS One. 2015 Oct 26;10(10):e0140975. doi: 10.1371/journal.pone.0140975. eCollection 2015.
3 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.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
6 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
7 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.
8 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
9 Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.