Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0009 Transporter Info
Gene Name SLC22A3
Transporter Name Organic cation transporter 3
Gene ID
6581
UniProt ID
O75751

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.2: Basic helix-loop-helix factors

Click to Show/Hide the Full List of 2 TF(s) Regulating This DT

        MYC 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in embryonic stem cells condition [1]

TF Protein Name

 Myc proto-oncogene protein Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Myc proto-oncogene protein (MYC) has been reported to bind to the transcription of SLC22A3 gene in embryonic stem cells condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

        TCF4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in glioblastoma multiforme condition [2]

TF Protein Name

 Transcription factor 4 Transcription Factor Info

Affected Drug/Substrate

 Temozolomide

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor 4 (TCF4) has been reported to bind to the transcription of SLC22A3 gene in glioblastoma multiforme condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

Click to Show/Hide the Full List of 4 TF(s) Regulating This DT

        AR 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in prostate cancer condition [3]

TF Protein Name

 Androgen receptor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Androgen receptor (AR) has been reported to bind to the transcription of SLC22A3 gene in prostate cancer condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

       Transcriptional Phenomenon2

 Activation of SLC22A3 gene in castration-resistant prostate cancers condition [4]

TF Protein Name

 Androgen receptor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Androgen receptor (AR) has been reported to activate the transcription of SLC22A3 gene in castration-resistant prostate cancers condition, which leads to a increased expression of the drug transporter Organic cation transporter 3.

        HNF4A 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in health condition [5]

TF Protein Name

 Hepatocyte nuclear factor 4-alpha Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Hepatocyte nuclear factor 4-alpha (HNF4A) has been reported to bind to the transcription of SLC22A3 gene in health condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

        NR3C1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A3 gene in ER(-) breast cancer condition [6]

TF Protein Name

 Glucocorticoid receptor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Glucocorticoid receptor (NR3C1) has been reported to activate the transcription of SLC22A3 gene in ER(-) breast cancer condition, which leads to an increased expression of the drug transporter Organic cation transporter 3.

        PPARA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A3 gene in health condition [7]

TF Protein Name

 Peroxisome proliferator-activated receptor alpha Transcription Factor Info

Affected Drug/Substrate

 L-carnitine

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Kidney

Related DT Changes

 Up regulating

Experimental Material

 129S1/SvImJ mice

Detailed Description

 Peroxisome proliferator-activated receptor alpha (PPARA) has been reported to activate the transcription of SLC22A3 gene in health condition, which leads to an increased expression of the drug transporter Organic cation transporter 3.

      Class2.2: Other C4 zinc finger-type factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        GATA4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A3 gene in gastric cancer condition [8]

TF Protein Name

 Transcription factor GATA-4 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Transcription factor GATA-4 (GATA4) has been reported to activate the transcription of SLC22A3 gene in gastric cancer condition, which leads to an increased expression of the drug transporter Organic cation transporter 3.

      Class2.3: C2H2 zinc finger factors

Click to Show/Hide the Full List of 4 TF(s) Regulating This DT

        EGR1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in erythroleukemia condition [9]

TF Protein Name

 Early growth response protein 1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Early growth response protein 1 (EGR1) has been reported to bind to the transcription of SLC22A3 gene in erythroleukemia condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

        KLF5 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC22A3 gene [10]

TF Protein Name

 Krueppel-like factor 5 Transcription Factor Info

Tissue

 Colon; Pancreatic ductal

Related DT Changes

 Direct regulating

Experiment method

 TF-transporter regulations were collected from ChIP-Seq datasets.

Detailed Description

 Krueppel-like factor 5 (KLF5) can directly bind to the SLC22A3 gene, which in turn affects the expression or function of the drug transporter Organic cation transporter 3.

        MAZ 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC22A3 gene [11]

TF Protein Name

 Myc-associated zinc finger protein Transcription Factor Info

Tissue

 Liver

Related DT Changes

 Direct regulating

Experiment method

 TF-transporter regulations were collected from ChIP-Seq datasets.

Detailed Description

 Myc-associated zinc finger protein (MAZ) can directly bind to the SLC22A3 gene, which in turn affects the expression or function of the drug transporter Organic cation transporter 3.

        ZNF263 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC22A3 gene [12]

TF Protein Name

 Zinc finger protein 263 Transcription Factor Info

Tissue

 Kidney

Related DT Changes

 Direct regulating

Experiment method

 TF-transporter regulations were collected from ChIP-Seq datasets.

Detailed Description

 Zinc finger protein 263 (ZNF263) can directly bind to the SLC22A3 gene, which in turn affects the expression or function of the drug transporter Organic cation transporter 3.

TF Superclass3: Helix-turn-helix domains

      Class3.3: Fork head / winged helix factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        FOXA2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in health condition [5]

TF Protein Name

 Hepatocyte nuclear factor 3-beta Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Hepatocyte nuclear factor 3-beta (FOXA2) has been reported to bind to the transcription of SLC22A3 gene in health condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

TF Superclass6: Immunoglobulin fold

      Class6.3: p53 domain factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        TP63 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC22A3 gene in epithelial to mesenchymal transition condition [13]

TF Protein Name

 Tumor protein 63 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Tumor protein 63 (TP63) has been reported to bind to the transcription of SLC22A3 gene in epithelial to mesenchymal transition condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

       Transcriptional Phenomenon2

 Binding to SLC22A3 gene in health condition [14]

TF Protein Name

 Tumor protein 63 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Tumor protein 63 (TP63) has been reported to bind to the transcription of SLC22A3 gene in health condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.

      Class6.4: Runt domain factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        RUNX2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A3 gene in prostate cancer condition [15]

TF Protein Name

 Runt-related transcription factor 2 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Runt-related transcription factor 2 (RUNX2) has been reported to activate the transcription of SLC22A3 gene in prostate cancer condition, which leads to an increased expression of the drug transporter Organic cation transporter 3.

TF Superclass7: beta-Hairpin exposed by an alpha/beta-scaffold

      Class7.1: SMAD/NF-1 DNA-binding domain factors

Click to Show/Hide the Full List of 1 TF(s) Regulating This DT

        SMAD4 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC22A3 gene in hESCs condition [16]

TF Protein Name

 Mothers against decapentaplegic homolog 4 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Mothers against decapentaplegic homolog 4 (SMAD4) has been reported to activate the transcription of SLC22A3 gene in human embryonic stem cells (hESCs) condition, which leads to an increased expression of the drug transporter Organic cation transporter 3.

       Transcriptional Phenomenon2

 Binding to SLC22A3 gene in epithelial ovarian cancer condition [17]

TF Protein Name

 Mothers against decapentaplegic homolog 4 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Mothers against decapentaplegic homolog 4 (SMAD4) has been reported to bind to the transcription of SLC22A3 gene in epithelial ovarian cancer condition, which leads to an affected expression of the drug transporter Organic cation transporter 3.
References
1 Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-Myc. PLoS One. 2009;4(11):e7839.
2 Unique genome-wide map of TCF4 and STAT3 targets using ChIP-seq reveals their association with new molecular subtypes of glioblastoma. Neuro Oncol. 2013;15(3):279-89.
3 Inhibition of p53 expression modifies the specificity of chromatin binding by the androgen receptor. Oncotarget. 2012;3(2):183-94.
4 Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer. Oncogene. 2012;31(17):2153-63.
5 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
6 Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. Cancer Res. 2011;71(20):6360-70.
7 PPAR alpha mediates transcriptional upregulation of novel organic cation transporters-2 and -3 and enzymes involved in hepatic carnitine synthesis. Exp Biol Med (Maywood). 2008 Mar;233(3):356-65.
8 Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development. Gut. 2015;64(5):707-19.
9 Global analysis of in vivo EGR1-binding sites in erythroleukemia cell using chromatin immunoprecipitation and massively parallel sequencing. Electrophoresis. 2010;31(17):2936-43.
10 NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013 Jan;41(D1):D991-5.
11 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-318. (ID:ENSG00000146477)
12 Closure of the NCBI SRA and implications for the long-term future of genomics data storage. Genome Biol. 2011;12(3):402.
13 p63 attenuates epithelial to mesenchymal potential in an experimental prostate cell model. PLoS One. 2013;8(5):e62547.
14 Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation. Nucleic Acids Res. 2012;40(15):7190-206.
15 Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion. Nucleic Acids Res. 2012;40(8):3538-47.
16 Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. Dev Biol. 2011;357(2):492-504.
17 ChIP-seq defined genome-wide map of TGF/SMAD4 targets: implications with clinical outcome of ovarian cancer. PLoS One. 2011;6(7):e22606.

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