Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0455 Transporter Info
Gene Name SLC6A3
Transporter Name Sodium-dependent dopamine transporter
Gene ID
6531
UniProt ID
Q01959

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

        HEY1 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC6A3 gene in brain neuroblastoma condition [1]

TF Protein Name

 Hairy/enhancer-of-split related with YRPW motif protein 1 Transcription Factor Info

Studied Phenotype

 Brain neuroblastoma [ICD11: 2A00.11]

Tissue

 Brain

Related DT Changes

 Down regulating

Experimental Material

 Human neuroblastoma cells (SH-SY5Y)

Detailed Description

 Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) has been reported to repress the transcription of SLC6A3 gene in brain neuroblastoma condition, which leads to a decreased expression of the drug transporter Sodium-dependent dopamine transporter.

       Transcriptional Phenomenon2

 Repression of SLC6A3 gene in health condition [2]

TF Protein Name

 Hairy/enhancer-of-split related with YRPW motif protein 1 Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Brain

Related DT Changes

 Down regulating

Experimental Material

 C57BL/6-129/Sv hybrid mice

Detailed Description

 Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) has been reported to repress the transcription of SLC6A3 gene in health condition, which leads to a decreased expression of the drug transporter Sodium-dependent dopamine transporter.

        MITF 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in melanoma condition [3]

TF Protein Name

 Microphthalmia-associated transcription factor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Microphthalmia-associated transcription factor (MITF) has been reported to activate the transcription of SLC6A3 gene in melanoma condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

      Class1.3: Basic helix-span-helix factors

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

        TFAP2C 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in breast cancer condition [4]

TF Protein Name

 Transcription factor AP-2 gamma Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Transcription factor AP-2 gamma (TFAP2C) has been reported to activate the transcription of SLC6A3 gene in breast cancer condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

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

        NR4A2 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in health condition [5]

TF Protein Name

 Nuclear receptor subfamily 4 group A member 2 Transcription Factor Info

Affected Drug/Substrate

 Dopamine

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 E12.5 mice

Detailed Description

 Nuclear receptor subfamily 4 group A member 2 (NR4A2) has been reported to activate the transcription of SLC6A3 gene in health condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

       Transcriptional Phenomenon2

 Activation of SLC6A3 gene in nicotine dependence condition [6]

TF Protein Name

 Nuclear receptor subfamily 4 group A member 2 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Nuclear receptor subfamily 4 group A member 2 (NR4A2) has been reported to activate the transcription of SLC6A3 gene in nicotine dependence condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

        PPARD 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC6A3 gene in myofibroblast condition [7]

TF Protein Name

 Peroxisome proliferator-activated receptor delta Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Peroxisome proliferator-activated receptor delta (PPARD) has been reported to repress the transcription of SLC6A3 gene in myofibroblast condition, which leads to a decreased expression of the drug transporter Sodium-dependent dopamine transporter.

      Class2.3: C2H2 zinc finger factors

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

        EGR1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC6A3 gene in erythroleukemia condition [8]

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 SLC6A3 gene in erythroleukemia condition, which leads to an affected expression of the drug transporter Sodium-dependent dopamine transporter.

        ZBTB14 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in adrenal gland pheochromocytoma condition [9]

TF Protein Name

 Zinc finger and BTB domain-containing protein 14 Transcription Factor Info

Studied Phenotype

 Adrenal gland pheochromocytoma [ICD11: 2D11.1]

Tissue

 Adrenal gland

Related DT Changes

 Up regulating

Experimental Material

 Rat adrenal gland pheochromocytoma cells (PC12)

Detailed Description

 Zinc finger and BTB domain-containing protein 14 (ZBTB14) has been reported to activate the transcription of SLC6A3 gene in adrenal gland pheochromocytoma condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

TF Superclass3: Helix-turn-helix domains

      Class3.1: Homeo domain factors

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

        OTP 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in health condition [10]

TF Protein Name

 Homeobox protein orthopedia Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Embryo

Related DT Changes

 Up regulating

Experimental Material

 Zebrafish

Detailed Description

 Homeobox protein orthopedia (OTP) has been reported to activate the transcription of SLC6A3 gene in health condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

        PITX3 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in health condition [11]

TF Protein Name

 Pituitary homeobox 3 Transcription Factor Info

Affected Drug/Substrate

 Dopamine

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 C57BL/6 Pitx3 KO mice

Detailed Description

 Pituitary homeobox 3 (PITX3) has been reported to activate the transcription of SLC6A3 gene in health condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

      Class3.5: Tryptophan cluster factors

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

        ELF1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC6A3 gene [12]

TF Protein Name

 ETS-related transcription factor Elf-1 Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 ETS-related transcription factor Elf-1 (ELF1) has been reported to bind to the transcription of SLC6A3 gene in . condition, which leads to a affected expression of the drug transporter Sodium-dependent dopamine transporter.

TF Superclass6: Immunoglobulin fold

      Class6.2: STAT domain factors

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

        STAT6 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 gene in health condition [13]

TF Protein Name

 Signal transducer and activator of transcription 6 Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Brain

Related DT Changes

 Up regulating

Experimental Material

 Sata6 KO mice

Detailed Description

 Signal transducer and activator of transcription 6 (STAT6) has been reported to activate the transcription of SLC6A3 gene in health condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.

      Class6.4: Runt domain factors

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

        RUNX1 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to SLC6A3 gene in health condition [14]

TF Protein Name

 Runt-related transcription factor 1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Runt-related transcription factor 1 (RUNX1) has been reported to bind to the transcription of SLC6A3 gene in health condition, which leads to a affected expression of the drug transporter Sodium-dependent dopamine transporter.

        RUNX2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of SLC6A3 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 SLC6A3 gene in prostate cancer condition, which leads to an increased expression of the drug transporter Sodium-dependent dopamine transporter.
References
1 Identification and characterization of the Hesr1/Hey1 as a candidate trans-acting factor on gene expression through the 3' non-coding polymorphic region of the human dopamine transporter (DAT1) gene. J Biochem. 2005 Feb;137(2):205-16.
2 Hesr1 knockout mice exhibit behavioral alterations through the dopaminergic nervous system. J Neurosci Res. 2006 Nov 15;84(7):1555-63.
3 Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma. Oncogene. 2011;30(20):2319-32.
4 Identification of primary gene targets of TFAP2C in hormone responsive breast carcinoma cells. Genes Chromosomes Cancer. 2010;49(10):948-62.
5 Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur J Neurosci. 2003 Oct;18(7):1731-8.
6 Dopamine genes and nicotine dependence in treatment-seeking and community smokers. Neuropsychopharmacology. 2009;34(10):2252-64.
7 Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor. PLoS One. 2011;6(1):e16344.
8 Global analysis of in vivo EGR1-binding sites in erythroleukemia cell using chromatin immunoprecipitation and massively parallel sequencing. Electrophoresis. 2010;31(17):2936-43.
9 Human zinc finger protein 161, a novel transcriptional activator of the dopamine transporter. Biochem Biophys Res Commun. 2004 Jan 23;313(4):969-76.
10 Orthopedia homeodomain protein is essential for diencephalic dopaminergic neuron development. Curr Biol. 2007 May 15;17(10):873-80.
11 Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons. J Neurochem. 2009 Dec;111(5):1202-12.
12 Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo. EMBO J. 2010;29(13):2147-60.
13 Down-regulation of dopamine transporter and abnormal behavior in STAT6-deficient mice. Int J Mol Med. 2005 May;15(5):819-25.
14 Genome-wide analyses reveal properties of redundant and specific promoter occupancy within the ETS gene family. Genes Dev. 2007;21(15):1882-94.
15 Genome-wide Runx2 occupancy in prostate cancer cells suggests a role in regulating secretion. Nucleic Acids Res. 2012;40(8):3538-47.

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