Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0446 Transporter Info
Gene Name SLC6A14
Transporter Name Amino acid transporter ATB0+
Gene ID
11254
UniProt ID
Q9UN76
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 Estradiol affects the expression of SLC6A14 mRNA [25]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Estradiol results in increased expression of SLC6A14 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone results in increased expression of SLC6A14 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Coumestrol co-treated with Resveratrol results in increased expression of SLC6A14 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene results in increased methylation of SLC6A14 3' UTR [22]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Benzo(a)pyrene results in increased methylation of SLC6A14 promoter [22]

Regulation Mechanism

 Transcription Factor Info

  1-Methyl-3-isobutylxanthine

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

  DT Modulation1

 Dexamethasone co-treated with 8-Bromo Cyclic Adenosine Monophosphate co-treated with 1-Methyl-3-isobutylxanthine results in increased expression of SLC6A14 mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  2,3-bis(3'-hydroxybenzyl)butyrolactone

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

  DT Modulation1

 Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone results in increased expression of SLC6A14 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

  7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide

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

  DT Modulation1

 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide results in increased expression of SLC6A14 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  8-Bromo Cyclic Adenosine Monophosphate

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

  DT Modulation1

 Dexamethasone co-treated with 8-Bromo Cyclic Adenosine Monophosphate co-treated with 1-Methyl-3-isobutylxanthine results in increased expression of SLC6A14 mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  abrine

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

  DT Modulation1

 abrine results in decreased expression of SLC6A14 mRNA [20]

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 increased expression of SLC6A14 mRNA [2]

Regulation Mechanism

 Transcription Factor Info

  Cadmium Chloride

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

  DT Modulation1

 Cadmium Chloride results in increased abundance of Cadmium which results in increased expression of SLC6A14 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

  cyfluthrin

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

  DT Modulation1

 cyfluthrin results in decreased expression of SLC6A14 protein [11]

Regulation Mechanism

 Transcription Factor Info

  Dexamethasone

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

  DT Modulation1

 Dexamethasone co-treated with 8-Bromo Cyclic Adenosine Monophosphate co-treated with 1-Methyl-3-isobutylxanthine results in increased expression of SLC6A14 mRNA [19]

Regulation Mechanism

 Transcription Factor Info

  dicrotophos

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

  DT Modulation1

 dicrotophos results in decreased expression of SLC6A14 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

  formononetin

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

  DT Modulation1

 formononetin results in decreased expression of SLC6A14 mRNA [26]

Regulation Mechanism

 Transcription Factor Info

  Furaldehyde

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

  DT Modulation1

 Furaldehyde co-treated with pyrogallol 1,3-dimethyl ether results in decreased expression of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Sodium Chloride co-treated with Furaldehyde results in decreased expression of and affects the localization of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Sodium Chloride co-treated with Furaldehyde results in decreased expression of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  Lactic Acid

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

  DT Modulation1

 Lactic Acid results in decreased expression of SLC6A14 mRNA [17]

Regulation Mechanism

 Transcription Factor Info

  pirinixic acid

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

  DT Modulation1

 pirinixic acid binds to and results in increased activity of PPARA protein which results in increased expression of SLC6A14 mRNA [28]

Regulation Mechanism

 Transcription Factor Info

  pyrogallol 1,3-dimethyl ether

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

  DT Modulation1

 Furaldehyde co-treated with pyrogallol 1,3-dimethyl ether results in decreased expression of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Sodium Chloride co-treated with pyrogallol 1,3-dimethyl ether results in increased expression of and affects the localization of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  sodium arsenite

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

  DT Modulation1

 sodium arsenite results in decreased expression of SLC6A14 mRNA [18]

Regulation Mechanism

 Transcription Factor Info

  Sodium Chloride

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

  DT Modulation1

 Sodium Chloride co-treated with Furaldehyde results in decreased expression of and affects the localization of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation2

 Sodium Chloride co-treated with Furaldehyde results in decreased expression of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation3

 Sodium Chloride co-treated with pyrogallol 1,3-dimethyl ether results in increased expression of and affects the localization of SLC6A14 protein [27]

Regulation Mechanism

 Transcription Factor Info

  tert-Butylhydroperoxide

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

  DT Modulation1

 tert-Butylhydroperoxide affects the expression of SLC6A14 mRNA [5]

Regulation Mechanism

 Transcription Factor Info

  Tetrachlorodibenzodioxin

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

  DT Modulation1

 Tetrachlorodibenzodioxin results in decreased expression of SLC6A14 mRNA [29]

Regulation Mechanism

 Transcription Factor Info

  urushiol

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

  DT Modulation1

 urushiol results in increased expression of SLC6A14 mRNA [30]

Regulation Mechanism

 Transcription Factor Info

  Vitamin K 3

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

  DT Modulation1

 Vitamin K 3 affects the expression of SLC6A14 mRNA [5]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Bortezomib

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

  DT Modulation1

 Bortezomib inhibits the activity of SLC6A14 [1]

Cell System

 Human embryonic kidney 293 cells (HEK293)-ATB0

  Diethylstilbestrol

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

  DT Modulation1

 Diethylstilbestrol increases the expression of SLC6A14 [2]

  Ampicillin

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

  DT Modulation1

 Ampicillin increases the expression of SLC6A14 [3]

  Azathioprine

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

  DT Modulation1

 Azathioprine inhibits the expression of SLC6A14 [4]

  Hydrogen Peroxide

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

  DT Modulation1

 Hydrogen Peroxide affects the expression of SLC6A14 [5]

  Menadione

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

  DT Modulation1

 Menadione affects the expression of SLC6A14 [5]

  Cyclosporine

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

  DT Modulation1

 Cyclosporine inhibits the expression of SLC6A14 [6]

  Urethane

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

  DT Modulation1

 Urethane inhibits the expression of SLC6A14 [7]

  Doxorubicin

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

  DT Modulation1

 Doxorubicin inhibits the expression of SLC6A14 [8]

  Estradiol

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

  DT Modulation1

 Estradiol inhibits the expression of SLC6A14 [9]

Drug in Phase 2 Trial

  Bisphenol A

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

  DT Modulation1

 Bisphenol A increases the expression of SLC6A14 [10]

  Genistein

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

  DT Modulation1

 Genistein increases the expression of SLC6A14 [10]

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 inhibits the expression of SLC6A14 [18]

Investigative Drug

  Coumestrol

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

  DT Modulation1

 Coumestrol increases the expression of SLC6A14 [12]

  Milchsaure

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

  DT Modulation1

 Milchsaure inhibits the expression of SLC6A14 [17]

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 SLC6A14 [15]

Natural Product

  Tobacco Smoke Pollution

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

  DT Modulation1

 Tobacco Smoke Pollution affects the expression of SLC6A14 [16]

  Caffeine

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

  DT Modulation1

 Caffeine results in decreased phosphorylation of SLC6A14 protein [24]

Regulation Mechanism

 Transcription Factor Info

  Resveratrol

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

  DT Modulation1

 Coumestrol co-treated with Resveratrol results in increased expression of SLC6A14 mRNA [12]

Regulation Mechanism

 Transcription Factor Info

Environmental toxicant

  Polychlorinated dibenzodioxin

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

  DT Modulation1

 Polychlorinated dibenzodioxin inhibits the expression of SLC6A14 [3]

Mycotoxins

  Aflatoxin B1

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

  DT Modulation1

 Aflatoxin B1 inhibits the expression of SLC6A14 [3]

  DT Modulation2

 Aflatoxin B1 results in decreased methylation of SLC6A14 gene [21]

Regulation Mechanism

 Transcription Factor Info

Carcinogen

  Polychlorinated Biphenyls

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

  DT Modulation1

 Polychlorinated Biphenyls increases the expression of SLC6A14 [10]

  Benzo(a)pyrene

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

  DT Modulation1

 Benzo(a)pyrene increases the expression of SLC6A14 [13]

  Cadmium

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

  DT Modulation1

 Cadmium Chloride results in increased abundance of Cadmium which results in increased expression of SLC6A14 mRNA [23]

Regulation Mechanism

 Transcription Factor Info

Pesticide/Insecticide

  Cyfluthrin

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

  DT Modulation1

 Cyfluthrin inhibits the expression of SLC6A14 [11]

  Dicrotophos

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

  DT Modulation1

 Dicrotophos inhibits the expression of SLC6A14 [14]

Health and Environmental Toxicant

  Zeranol

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

  DT Modulation1

 Zeranol increases the expression of SLC6A14 [2]
References
1 Trafficking of the amino acid transporter B0,+(SLC6A14) to the plasma membrane involves an exclusive interaction with SEC24C for its exit from the endoplasmic reticulum. Biochim Biophys Acta Mol Cell Res. 2019 Feb;1866(2):252-263.
2 Oestrogenic potencies of Zeranol, oestradiol, diethylstilboestrol, Bisphenol-A and genistein: implications for exposure assessment of potential endocrine disrupters. Hum Reprod. 2001 May;16(5):1037-45.
3 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
4 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
5 Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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 17 beta-Estradiol Activates HSF1 via MAPK Signaling in ER alpha-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533.
10 Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
11 The common insecticides cyfluthrin and chlorpyrifos alter the expression of a subset of genes with diverse functions in primary human astrocytes. Toxicol Sci. 2006 Sep;93(1):125-35.
12 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
13 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
14 Molecular mechanisms of discrotophos-induced toxicity in HepG2 cells: The role of CSA in oxidative stress. Food Chem Toxicol. 2017 May;103:253-260.
15 Inhibition of histone H3K27 demethylases selectively modulates inflammatory phenotypes of natural killer cells. J Biol Chem. 2018 Feb 16;293(7):2422-2437.
16 Multi-omics analysis: Repeated exposure of a 3D bronchial tissue culture to whole-cigarette smoke. Toxicol In Vitro. 2019 Feb;54:251-262.
17 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
18 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.
19 Role of endogenous TGF-beta in glucocorticoid-induced lung type II cell differentiation. Am J Physiol Lung Cell Mol Physiol. 2007;292(1):L249-57.
20 Integration of transcriptomics, proteomics and metabolomics data to reveal the biological mechanisms of abrin injury in human lung epithelial cells. Toxicol Lett. 2019;312:1-10.
21 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
22 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
23 Cadmium Exposure Inhibits Branching Morphogenesis and Causes Alterations Consistent With HIF-1 Inhibition in Human Primary Breast Organoids. Toxicol Sci. 2018;164(2):592-602.
24 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022;449:116110.
25 Research Resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014;28(12):2072-81.
26 Identification of formononetin as the active compound of CR-SR in hepatocellular carcinoma treatment: An integrated approach combining network pharmacology and weighted gene co-expression networks. Chem Biol Drug Des. 2024;103(1):e14363.
27 Human Keratinocyte Responses to Woodsmoke Chemicals. Chem Res Toxicol. 2024;37(5):675-684.
28 Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One. 2009;4(8):e6796.
29 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.
30 CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020;386:114828.

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