Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0331 Transporter Info
Gene Name SLC38A4
Transporter Name Sodium-coupled neutral amino acid transporter 4
Gene ID
55089
UniProt ID
Q969I6

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.3: Basic helix-span-helix factors

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

        TFAP2A 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 gene in MCF7 cells [1]

TF Protein Name

 Transcription factor AP-2-alpha Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor AP-2-alpha (TFAP2A) has been reported to bind to the transcription of SLC38A4 gene in MCF7 cells, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

        TFAP2C 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC38A4 gene in severe placental abnormalities condition [2]

TF Protein Name

 Transcription factor AP-2 gamma Transcription Factor Info

Studied Phenotype

 Severe placental abnormalities [ICD11: JA8A.1]

Tissue

 Placenta

Related DT Changes

 Down regulating

Experimental Material

 129-SV Tpbpa-Cre transgenic mice

Detailed Description

 Transcription factor AP-2 gamma (TFAP2C) has been reported to repress the transcription of SLC38A4 gene in severe placental abnormalities condition, which leads to a decreased expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

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 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 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 SLC38A4 gene in prostate cancer condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

        HNF4A 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 gene in health condition [4]

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 SLC38A4 gene in health condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

        PPARD 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC38A4 gene in myofibroblasts condition [5]

TF Protein Name

 Peroxisome proliferator-activated receptor delta Transcription Factor Info

Related DT Changes

 Down regulating

Detailed Description

 Peroxisome proliferator-activated receptor delta (PPARD) has been reported to repress the transcription of SLC38A4 gene in myofibroblasts condition, which leads to a decreased expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

       Transcriptional Phenomenon2

 Repression of SLC38A4 gene in breast cancer condition [6]

TF Protein Name

 Peroxisome proliferator-activated receptor delta Transcription Factor Info

Affected Drug/Substrate

 ST247 and DG172

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Peroxisome proliferator-activated receptor delta (PPARD) has been reported to repress the transcription of SLC38A4 gene in breast cancer condition, which leads to a decreased expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

        RARA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC38A4 gene in teratocarcinoma condition [7]

TF Protein Name

 Retinoic acid receptor alpha Transcription Factor Info

Studied Phenotype

 Teratocarcinoma [ICD11: 2C12.0Y]

Tissue

 Embryo

Related DT Changes

 Down regulating

Experimental Material

 Mouse teratocarcinoma cells (F9)

Detailed Description

 Retinoic acid receptor alpha (RARA) has been reported to repress the transcription of SLC38A4 gene in teratocarcinoma condition, which leads to a decreased expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

      Class2.2: Other C4 zinc finger-type factors

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

        GATA6 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC38A4 gene in gastric cancer condition [8]

TF Protein Name

 Transcription factor GATA-6 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Transcription factor GATA-6 (GATA6) has been reported to activate the transcription of SLC38A4 gene in gastric cancer condition, which leads to an increased expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

      Class2.3: C2H2 zinc finger factors

Click to Show/Hide the Full List of 3 TF(s) Regulating This DT

        MAZ 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to SLC38A4 gene [9]

TF Protein Name

 Myc-associated zinc finger protein Transcription Factor Info

Tissue

 Blood; Bone marrow; Lung

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 SLC38A4 gene, which in turn affects the expression or function of the drug transporter Sodium-coupled neutral amino acid transporter 4.

        PEG3 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC38A4 gene in health condition [10]

TF Protein Name

 Paternally-expressed gene 3 protein Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Brain

Related DT Changes

 Down regulating

Experimental Material

 C57BL/6J mice

Detailed Description

 Paternally-expressed gene 3 protein (PEG3) has been reported to repress the transcription of SLC38A4 gene in health condition, which leads to a decreased expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

        ZNF217 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 gene in breast cancer condition [11]

TF Protein Name

 Zinc finger protein 217 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Zinc finger protein 217 (ZNF217) has been reported to bind to the transcription of SLC38A4 gene in breast cancer condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

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 SLC38A4 gene in health condition [4]

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 SLC38A4 gene in health condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

TF Superclass6: Immunoglobulin fold

      Class6.1: Rel homology region factors

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

        RBPJ 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 gene in immortal lymphoblast cell lines (LCLs) condition [12]

TF Protein Name

 Recombining binding protein suppressor of hairless Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Recombining binding protein suppressor of hairless (RBPJ) has been reported to bind to the transcription of SLC38A4 gene in immortal lymphoblast cell lines (LCLs) condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

      Class6.2: STAT domain factors

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

        STAT3 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 gene in glioblastoma multiforme condition [13]

TF Protein Name

 Signal transducer and activator of transcription 3 Transcription Factor Info

Affected Drug/Substrate

 Temozolomide

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Signal transducer and activator of transcription 3 (STAT3) has been reported to bind to the transcription of SLC38A4 gene in glioblastoma multiforme condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

      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 SLC38A4 gene in epithelial to mesenchymal transition 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 SLC38A4 gene in epithelial to mesenchymal transition condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

       Transcriptional Phenomenon2

 Binding to SLC38A4 gene in health condition [15]

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 SLC38A4 gene in health condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.

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 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC38A4 gene in epithelial ovarian cancer condition [16]

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 SLC38A4 gene in epithelial ovarian cancer condition, which leads to an affected expression of the drug transporter Sodium-coupled neutral amino acid transporter 4.
References
1 A computational genomics approach to identify cis-regulatory modules from chromatin immunoprecipitation microarray data--a case study using E2F1. Genome Res. 2006;16(12):1585-95.
2 Tpbpa-Cre-mediated deletion of TFAP2C leads to deregulation of Cdkn1a, Akt1 and the ERK pathway, causing placental growth arrest. Development. 2016 Mar 1;143(5):787-98.
3 Inhibition of p53 expression modifies the specificity of chromatin binding by the androgen receptor. Oncotarget. 2012;3(2):183-94.
4 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
5 Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor. PLoS One. 2011;6(1):e16344.
6 Inverse PPAR agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene. 2013;32(44):5241-52.
7 Epigenetic regulation by RAR-alpha maintains ligand-independent transcriptional activity. Nucleic Acids Res. 2012 Jan;40(1):102-15.
8 Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development. Gut. 2015;64(5):707-19.
9 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-288. (ID:ENSG00000139209)
10 DNA-Binding Motif of the Imprinted Transcription Factor PEG3. PLoS One. 2015 Dec 21;10(12):e0145531.
11 Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha. BMC Genomics. 2014;15(1):520.
12 Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth. Proc Natl Acad Sci U S A. 2011;108(36):14902-7.
13 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.
14 p63 attenuates epithelial to mesenchymal potential in an experimental prostate cell model. PLoS One. 2013;8(5):e62547.
15 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.
16 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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