Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0545 Transporter Info
Gene Name KCNK2
Transporter Name Potassium channel subfamily K member 2
Gene ID
3776
UniProt ID
O95069
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Mycotoxins

  Aflatoxin B1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 results in increased methylation of KCNK2 intron [11]

Regulation Mechanism

 Transcription Factor Info

Chemical Compound

  Arachidonic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Arachidonic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  aristolochic acid I

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 aristolochic acid I results in decreased expression of KCNK2 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Asbestos, Serpentine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Asbestos, Serpentine results in decreased methylation of KCNK2 gene [14]

Regulation Mechanism

 Transcription Factor Info

  Benzo(a)pyrene

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene affects the methylation of KCNK2 exon [15]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene affects the methylation of KCNK2 intron [11]

Regulation Mechanism

 Transcription Factor Info

  benzo(e)pyrene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 benzo(e)pyrene affects the methylation of KCNK2 intron [11]

Regulation Mechanism

 Transcription Factor Info

  bisphenol A

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 bisphenol A results in decreased methylation of KCNK2 gene [16]

Regulation Mechanism

 Transcription Factor Info

  Camptothecin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 KCNK2 mRNA results in decreased susceptibility to Camptothecin [17]

Regulation Mechanism

 Transcription Factor Info

  CGP 52608

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 CGP 52608 promotes the reaction RORA protein binds to KCNK2 gene [18]

Regulation Mechanism

 Transcription Factor Info

  Copper

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NSC 689534 binds to Copper which results in decreased expression of KCNK2 mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  Diltiazem

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Diltiazem inhibits the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  Flufenamic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Flufenamic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  FR900359

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 FR900359 results in increased phosphorylation of KCNK2 protein [20]

Regulation Mechanism

 Transcription Factor Info

  Halothane

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Halothane promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  lead acetate

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 lead acetate results in decreased expression of KCNK2 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  Mefenamic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Mefenamic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  Methapyrilene

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Methapyrilene affects the methylation of KCNK2 intron [11]

Regulation Mechanism

 Transcription Factor Info

  Niflumic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Niflumic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  NSC 689534

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 NSC 689534 binds to Copper which results in decreased expression of KCNK2 mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  Potassium

            6 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Arachidonic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Diltiazem inhibits the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Flufenamic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation4

 Halothane promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation5

 Mefenamic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation6

 Niflumic Acid promotes the reaction KCNK2 protein results in increased transport of Potassium [12]

Regulation Mechanism

 Transcription Factor Info

  potassium chromate(VI)

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 potassium chromate(VI) results in increased expression of KCNK2 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  S-(1,2-dichlorovinyl)cysteine

            3 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 S-(1,2-dichlorovinyl)cysteine affects the susceptibility to Lipopolysaccharides which results in increased expression of KCNK2 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 S-(1,2-dichlorovinyl)cysteine co-treated with Lipopolysaccharides results in increased expression of KCNK2 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 S-(1,2-dichlorovinyl)cysteine results in increased expression of KCNK2 mRNA [24]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 sodium arsenite results in decreased expression of KCNK2 mRNA [21]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 sodium arsenite results in increased expression of KCNK2 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

  Vanadates

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Vanadates results in increased expression of KCNK2 mRNA [22]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Dasatinib

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Dasatinib inhibits the expression of KCNK2 [2]

  Arsenic Trioxide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Arsenic Trioxide inhibits the expression of KCNK2 [3]

  Fluoxetine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Fluoxetine inhibits the activity of KCNK2 [1]

Drug in Phase 2 Trial

  Genistein

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Genistein inhibits the expression of KCNK2 [7]

Drug in Phase 1 Trial

  Sodium arsenite

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sodium arsenite increases the expression of KCNK2 [10]

Drug in Preclinical Test

  (+)-JQ1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 (+)-JQ1 inhibits the expression of KCNK2 [6]

Discontinued Drug

  Sipatrigine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Sipatrigine inhibits the activity of KCNK2 [1]

Cell System

 Human embryonic kidney 293 cells (HEK293)-KCNK2

Patented Pharmaceutical Agent

  GSK-J4

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 GSK-J4 increases the expression of KCNK2 [8]

Natural Product

  14-deoxy-11,12-didehydroandrographolide

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 14-deoxy-11,12-didehydroandrographolide inhibits the expression of KCNK2 [4]

  Tobacco Smoke Pollution

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tobacco Smoke Pollution inhibits the expression of KCNK2 [9]

  Resveratrol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Plant Extracts co-treated with Resveratrol results in decreased expression of KCNK2 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

Acute Toxic Substance

  Cadmium

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Cadmium inhibits the expression of KCNK2 [5]
References
1 Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target? J Med Chem. 2016 Jun 9;59(11):5149-57.
2 Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
3 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
4 Identification of genes involved in the regulation of 14-deoxy-11,12-didehydroandrographolide-induced toxicity in T-47D mammary cells. Food Chem Toxicol. 2012 Feb;50(2):431-44.
5 Using expression profiling to understand the effects of chronic cadmium exposure on MCF-7 breast cancer cells. PLoS One. 2013 Dec 20;8(12):e84646.
6 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
7 Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein. Toxicol Sci. 2016 May;151(1):71-87.
8 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J Biol Chem. 2018 Feb 16;293(7):2422-2437.
9 Integration of transcriptome analysis with pathophysiological endpoints to evaluate cigarette smoke toxicity in an in vitro human airway tissue model. Arch Toxicol. 2021 May;95(5):1739-1761.
10 Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer. Arch Toxicol. 2021 Jul;95(7):2351-2365.
11 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018;121:214-223.
12 Fenamates and diltiazem modulate lipid-sensitive mechano-gated 2P domain K(+) channels. Pflugers Arch. 2005;451(3):474-8.
13 Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells. Toxicol In Vitro. 2021;70:105054.
14 DNA methylation profiling of asbestos-treated MeT5A cell line reveals novel pathways implicated in asbestos response. Arch Toxicol. 2018;92(5):1785-1795.
15 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
16 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019;11(1):138.
17 ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014;74(23):6968-79.
18 Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines. Exp Cell Res. 2017;353(1):6-15.
19 A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radic Biol Med. 2011 Jan 1;50(1):110-21.
20 Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses. Mol Cell Proteomics. 2023;22(11):100649.
21 High-Throughput Transcriptomics of Nontumorigenic Breast Cells Exposed to Environmentally Relevant Chemicals. Environ Health Perspect. 2024;132(4):47002.
22 Gene expression changes in human lung cells exposed to arsenic, chromium, nickel or vanadium indicate the first steps in cancer. Metallomics. 2012 Aug;4(8):784-93.
23 One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.
24 The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model. Toxicol In Vitro. 2022;84:105429.

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