Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX7NIQ5)

DOT Name Serine/threonine-protein kinase N3 (PKN3)
Synonyms EC 2.7.11.13; Protein kinase PKN-beta; Protein-kinase C-related kinase 3
Gene Name PKN3
UniProt ID
PKN3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.7.11.13
Pfam ID
PF02185 ; PF00069 ; PF00433
Sequence
MEEGAPRQPGPSQWPPEDEKEVIRRAIQKELKIKEGVENLRRVATDRRHLGHVQQLLRSS
NRRLEQLHGELRELHARILLPGPGPGPAEPVASGPRPWAEQLRARHLEALRRQLHVELKV
KQGAENMTHTCASGTPKERKLLAAAQQMLRDSQLKVALLRMKISSLEASGSPEPGPELLA
EELQHRLHVEAAVAEGAKNVVKLLSSRRTQDRKALAEAQAQLQESSQKLDLLRLALEQLL
EQLPPAHPLRSRVTRELRAAVPGYPQPSGTPVKPTALTGTLQVRLLGCEQLLTAVPGRSP
AAALASSPSEGWLRTKAKHQRGRGELASEVLAVLKVDNRVVGQTGWGQVAEQSWDQTFVI
PLERARELEIGVHWRDWRQLCGVAFLRLEDFLDNACHQLSLSLVPQGLLFAQVTFCDPVI
ERRPRLQRQERIFSKRRGQDFLRASQMNLGMAAWGRLVMNLLPPCSSPSTISPPKGCPRT
PTTLREASDPATPSNFLPKKTPLGEEMTPPPKPPRLYLPQEPTSEETPRTKRPHMEPRTR
RGPSPPASPTRKPPRLQDFRCLAVLGRGHFGKVLLVQFKGTGKYYAIKALKKQEVLSRDE
IESLYCEKRILEAVGCTGHPFLLSLLACFQTSSHACFVTEFVPGGDLMMQIHEDVFPEPQ
ARFYVACVVLGLQFLHEKKIIYRDLKLDNLLLDAQGFLKIADFGLCKEGIGFGDRTSTFC
GTPEFLAPEVLTQEAYTRAVDWWGLGVLLYEMLVGECPFPGDTEEEVFDCIVNMDAPYPG
FLSVQGLEFIQKLLQKCPEKRLGAGEQDAEEIKVQPFFRTTNWQALLARTIQPPFVPTLC
GPADLRYFEGEFTGLPPALTPPAPHSLLTARQQAAFRDFDFVSERFLEP
Function Contributes to invasiveness in malignant prostate cancer.
Tissue Specificity Expressed in prostate tumors and various cancer cell lines. Not expressed in adult tissues.
KEGG Pathway
PI3K-Akt sig.ling pathway (hsa04151 )
Reactome Pathway
RHOA GTPase cycle (R-HSA-8980692 )
RHOB GTPase cycle (R-HSA-9013026 )
RHOC GTPase cycle (R-HSA-9013106 )
RHO GTPases activate PKNs (R-HSA-5625740 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Serine/threonine-protein kinase N3 (PKN3). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Serine/threonine-protein kinase N3 (PKN3). [7]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Serine/threonine-protein kinase N3 (PKN3). [11]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [2]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [3]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [4]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Serine/threonine-protein kinase N3 (PKN3). [5]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [6]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [8]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [9]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase N3 (PKN3). [10]
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⏷ Show the Full List of 8 Drug(s)

References

1 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.
2 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.
3 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
4 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5 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.
6 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
7 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.
8 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
9 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
10 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.
11 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.