Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0452 Transporter Info
Gene Name SLC6A2
Transporter Name Sodium-dependent noradrenaline transporter
Gene ID
6530
UniProt ID
P23975

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.2: Basic helix-loop-helix factors

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        MYC 

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       Transcriptional Phenomenon1

 Binding to SLC6A2 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 SLC6A2 gene in embryonic stem cells condition, which leads to an affected expression of the drug transporter Sodium-dependent noradrenaline transporter.

      Class1.3: Basic helix-span-helix factors

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        TFAP2A 

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       Transcriptional Phenomenon1

 Binding to SLC6A2 gene in health condition [2]

TF Protein Name

 Transcription factor AP-2-alpha Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor AP-2-alpha (TFAP2A) has been reported to bind to the transcription of SLC6A2 gene in health condition, which leads to an affected expression of the drug transporter Sodium-dependent noradrenaline transporter.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

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        AR 

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       Transcriptional Phenomenon1

 Binding to SLC6A2 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 SLC6A2 gene in prostate cancer condition, which leads to an affected expression of the drug transporter Sodium-dependent noradrenaline transporter.

        NR3C1 

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       Transcriptional Phenomenon1

 Activation of SLC6A2 gene in brain neuroblastoma condition [4]

TF Protein Name

 Glucocorticoid receptor Transcription Factor Info

Studied Phenotype

 Brain neuroblastoma [ICD11: 2A00.11]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 human neuroblastoma cells (SK-N-BE(2)-M17)

Detailed Description

 Glucocorticoid receptor (NR3C1) has been reported to activate the transcription of SLC6A2 gene in brain neuroblastoma condition, which leads to an increased expression of the drug transporter Sodium-dependent noradrenaline transporter.

      Class2.3: C2H2 zinc finger factors

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        SCRT1 

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       Transcriptional Phenomenon1

 Repression of SLC6A2 gene in attention deficit hyperactivity disorder condition [5]

TF Protein Name

 Transcriptional repressor scratch 1 Transcription Factor Info

Studied Phenotype

 Attention deficit hyperactivity disorder [ICD11: 6A05]

Tissue

 Brain

Related DT Changes

 Down regulating

Experimental Material

 Human attention-deficit hyperactivity disorder cell isolates

Detailed Description

 Transcriptional repressor scratch 1 (SCRT1) has been reported to repress the transcription of SLC6A2 gene in attention deficit hyperactivity disorder condition, which leads to a decreased expression of the drug transporter Sodium-dependent noradrenaline transporter.

        SNAI2 

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       Transcriptional Phenomenon1

 Repression of SLC6A2 gene in attention deficit hyperactivity disorder condition [5]

TF Protein Name

 Zinc finger protein SNAI2 Transcription Factor Info

Studied Phenotype

 Attention deficit hyperactivity disorder [ICD11: 6A05]

Tissue

 Brain

Related DT Changes

 Down regulating

Experimental Material

 Human attention-deficit hyperactivity disorder cell isolates

Detailed Description

 Zinc finger protein SNAI2 (SNAI2) has been reported to repress the transcription of SLC6A2 gene in attention deficit hyperactivity disorder condition, which leads to a decreased expression of the drug transporter Sodium-dependent noradrenaline transporter.

TF Superclass3: Helix-turn-helix domains

      Class3.1: Homeo domain factors

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        HOXA5 

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       Transcriptional Phenomenon1

 Activation of SLC6A2 gene in brain neuroblastoma condition [6]

TF Protein Name

 Homeobox protein Hox-A5 Transcription Factor Info

Studied Phenotype

 Brain neuroblastoma [ICD11: 2A00.11]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 human neuroblastoma cells (SK-N-BE(2)-C)

Detailed Description

 Homeobox protein Hox-A5 (HOXA5) has been reported to activate the transcription of SLC6A2 gene in brain neuroblastoma condition, which leads to an increased expression of the drug transporter Sodium-dependent noradrenaline transporter.

        PHOX2A 

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       Transcriptional Phenomenon1

 Activation of SLC6A2 gene in brain neuroblastoma condition [6]

TF Protein Name

 Paired mesoderm homeobox protein 2A Transcription Factor Info

Studied Phenotype

 Brain neuroblastoma [ICD11: 2A00.11]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 human neuroblastoma cells (SK-N-BE(2)-C)

Detailed Description

 Paired mesoderm homeobox protein 2A (PHOX2A) has been reported to activate the transcription of SLC6A2 gene in brain neuroblastoma condition, which leads to an increased expression of the drug transporter Sodium-dependent noradrenaline transporter.

      Class3.3: Fork head / winged helix factors

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        FOXO3 

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       Transcriptional Phenomenon1

 Activation of SLC6A2 gene in DLD1 condition [7]

TF Protein Name

 Forkhead box protein O3 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Forkhead box protein O3 (FOXO3) has been reported to activate the transcription of SLC6A2 gene in DLD1 condition, which leads to an increased expression of the drug transporter Sodium-dependent noradrenaline transporter.

      Class3.5: Tryptophan cluster factors

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        FLI1 

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       Transcriptional Phenomenon1

 Binding to SLC6A2 gene in megakaryocytes condition [8]

TF Protein Name

 Friend leukemia integration 1 transcription factor Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Friend leukemia integration 1 transcription factor (FLI1) has been reported to bind to the transcription of SLC6A2 gene in megakaryocytes condition, which leads to an affected expression of the drug transporter Sodium-dependent noradrenaline transporter.

TF Superclass6: Immunoglobulin fold

      Class6.4: Runt domain factors

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        RUNX2 

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       Transcriptional Phenomenon1

 Activation of SLC6A2 gene in prostate cancer condition [9]

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 SLC6A2 gene in prostate cancer condition, which leads to an increased expression of the drug transporter Sodium-dependent noradrenaline transporter.

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

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

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        SMAD4 

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       Transcriptional Phenomenon1

 Activation of SLC6A2 gene in human embryonic stem cells (hESCs) condition [10]

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 SLC6A2 gene in human embryonic stem cells (hESCs) condition, which leads to an increased expression of the drug transporter Sodium-dependent noradrenaline transporter.
References
1 Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-Myc. PLoS One. 2009;4(11):e7839.
2 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.
3 Integrated expression profiling and ChIP-seq analyses of the growth inhibition response program of the androgen receptor. PLoS One. 2009;4(8):e6589.
4 Dexamethasone-induced up-regulation of the human norepinephrine transporter involves the glucocorticoid receptor and increased binding of C/EBP-beta to the proximal promoter of norepinephrine transporter. J Neurochem. 2011 Nov;119(3):654-63.
5 A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder. Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19164-9.
6 A proximal promoter domain containing a homeodomain-binding core motif interacts with multiple transcription factors, including HoxA5 and Phox2 proteins, and critically regulates cell type-specific transcription of the human norepinephrine transporter gene. J Neurosci. 2002 Apr 1;22(7):2579-89.
7 Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling. Mol Syst Biol. 2013;9:638.
8 Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev Cell. 2011;20(5):597-609.
9 Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion. Nucleic Acids Res. 2012;40(8):3538-47.
10 Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. Dev Biol. 2011;357(2):492-504.

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