Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0456 Transporter Info
Gene Name SLC6A4
Transporter Name Sodium-dependent serotonin transporter
Gene ID
6532
UniProt ID
P31645

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.2: Basic helix-loop-helix factors

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        MITF 

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       Transcriptional Phenomenon1

 Activation of SLC6A4 gene in melanoma condition [1]

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 SLC6A4 gene in melanoma condition, which leads to an increased expression of the drug transporter Sodium-dependent serotonin transporter.

      Class1.3: Basic helix-span-helix factors

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        TFAP2A 

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       Transcriptional Phenomenon1

 Direct binding to SLC6A4 gene [2]

TF Protein Name

 Transcription factor AP-2-alpha Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor AP-2-alpha (TFAP2A) can directly bind to the SLC6A4 gene, which in turn affects the expression or function of the drug transporter Sodium-dependent serotonin transporter.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

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        HNF4A 

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       Transcriptional Phenomenon1

 Binding to SLC6A4 gene in health condition [3]

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 SLC6A4 gene in health condition, which leads to an affected expression of the drug transporter Sodium-dependent serotonin transporter.

      Class2.2: Other C4 zinc finger-type factors

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        GATA1 

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       Transcriptional Phenomenon1

 Direct binding to SLC6A4 gene [4]

TF Protein Name

 Erythroid transcription factor Transcription Factor Info

Tissue

 Blood; Bone marrow

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Erythroid transcription factor (GATA1) can directly bind to the SLC6A4 gene, which in turn affects the expression or function of the drug transporter Sodium-dependent serotonin transporter.

      Class2.3: C2H2 zinc finger factors

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        CTCF 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of SLC6A4 gene in neurological conditions

TF Protein Name

 Transcriptional repressor CTCF Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Transcriptional repressor CTCF (CTCF) has been reported to repress the transcription of SLC6A4 gene in neurological conditions, which leads to a decreased expression of the drug transporter Sodium-dependent serotonin transporter.

       Transcriptional Phenomenon2

 Activation of SLC6A4 gene in gestational choriocarcinoma condition [5]

TF Protein Name

 Transcriptional repressor CTCF Transcription Factor Info

Studied Phenotype

 Gestational choriocarcinoma [ICD11: 2C75]

Tissue

 Trophoderm

Related DT Changes

 Up regulating

Experimental Material

 Human gestational choriocarcinoma cells (JAr)

Detailed Description

 Transcriptional repressor CTCF (CTCF) has been reported to activate the transcription of SLC6A4 gene in gestational choriocarcinoma condition, which leads to an increased expression of the drug transporter Sodium-dependent serotonin transporter.

TF Superclass3: Helix-turn-helix domains

      Class3.3: Fork head / winged helix factors

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        E2F1 

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       Transcriptional Phenomenon1

 Binding to SLC6A4 gene in MCF7 cells [2]

TF Protein Name

 Transcription factor E2F1 Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Transcription factor E2F1 (E2F1) has been reported to bind to the transcription of SLC6A4 gene in MCF7 cells, which leads to an affected expression of the drug transporter Sodium-dependent serotonin transporter.

      Class3.5: Tryptophan cluster factors

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        ERG 

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       Transcriptional Phenomenon1

 Direct binding to SLC6A4 gene [6]

TF Protein Name

 Transcriptional regulator ERG Transcription Factor Info

Tissue

 Aorta

Related DT Changes

 Direct regulating

Experiment method

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

Detailed Description

 Transcriptional regulator ERG (ERG) can directly bind to the SLC6A4 gene, which in turn affects the expression or function of the drug transporter Sodium-dependent serotonin transporter.

        FLI1 

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       Transcriptional Phenomenon1

 Binding to SLC6A4 gene in megakaryocytes condition [7]

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 SLC6A4 gene in megakaryocytes condition, which leads to an affected expression of the drug transporter Sodium-dependent serotonin 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 SLC6A4 gene in human embryonic stem cells (hESCs) condition [8]

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 SLC6A4 gene in human embryonic stem cells (hESCs) condition, which leads to an increased expression of the drug transporter Sodium-dependent serotonin transporter.

TF Superclass9: beta-Barrel DNA-binding domains

      Class9.1: Cold-shock domain factors

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        YBX1 

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       Transcriptional Phenomenon1

 Binding to SLC6A4 gene in affective disorders condition

TF Protein Name

 Y-box-binding protein 1 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Y-box-binding protein 1 (YBX1) has been reported to bind to the transcription of SLC6A4 gene in affective disorders condition, which leads to an affected expression of the drug transporter Sodium-dependent serotonin transporter.
References
1 Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma. Oncogene. 2011;30(20):2319-32.
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 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
4 NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013 Jan;41(D1):D991-5.
5 Differential regulation of the serotonin transporter gene by lithium is mediated by transcription factors, CCCTC binding protein and Y-box binding protein 1, through the polymorphic intron 2 variable number tandem repeat. J Neurosci. 2007 Mar 14;27(11):2793-801.
6 hTFtarget: A Comprehensive Database for Regulations of Human Transcription Factors and Their Targets. Genomics Proteomics Bioinformatics. 2020 Apr;18(2):120-206. (ID:ENSG00000108576)
7 Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev Cell. 2011;20(5):597-609.
8 Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. Dev Biol. 2011;357(2):492-504.

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