Detail Information of Transcriptional Regulations

General Information of Drug Transporter (DT)
DT ID DTD0014 Transporter Info
Gene Name ABCB11
Transporter Name Bile salt export pump
Gene ID
8647
UniProt ID
O95342

Transcriptional Regulation of This DT (TSR)

TF Superclass1: Basic domains

      Class1.1: Basic leucine zipper factors

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

        NFE2L2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in hepatoblastoma condition [1]

TF Protein Name

 Nuclear factor erythroid 2-related factor 2 Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Nuclear factor erythroid 2-related factor 2 (NFE2L2) has been reported to activate the transcription of ABCB11 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Bile salt export pump.

TF Superclass2: Zinc-coordinating DNA-binding domains

      Class2.1: Nuclear receptors with C4 zinc fingers

Click to Show/Hide the Full List of 8 TF(s) Regulating This DT

        HNF4A 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Direct binding to ABCB11 gene [2]

TF Protein Name

 Hepatocyte nuclear factor 4-alpha Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Hepatocyte nuclear factor 4-alpha (HNF4A) can directly bind to the ABCB11 gene, which in turn affects the expression or function of the drug transporter Bile salt export pump.

        mutated NR1H4 (T442E) 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in colon cancer condition [3]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Colon cancer [ICD11: 2B90]

Tissue

 Colon

Related DT Changes

 Up regulating

Experimental Material

 Human colon adenocarcinoma cells (Caco-2)

Detailed Description

 mutated Bile acid receptor (mutated NR1H4 (T442E)) has been reported to activate the transcription of ABCB11 gene in colon cancer condition, which leads to an increased expression of the drug transporter Bile salt export pump.

        NR1H4 

Click to Show/Hide to Show 4 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in hepatoblastoma condition [4]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Bile acid receptor (NR1H4) has been reported to activate the transcription of ABCB11 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon2

 Activation of ABCB11 gene in colon cancer condition [3]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Colon cancer [ICD11: 2B90]

Tissue

 Colon

Related DT Changes

 Up regulating

Experimental Material

 Human colon adenocarcinoma cells (Caco-2)

Detailed Description

 Bile acid receptor (NR1H4) has been reported to activate the transcription of ABCB11 gene in colon cancer condition, which leads to an increased expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon3

 Activation of ABCB11 gene in health condition [5]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Liver

Related DT Changes

 up regulating

Experimental Material

 C57/BL6 mice

Detailed Description

 Bile acid receptor (NR1H4), influenced by the exogenous guggulsterone, has been reported to activate the transcription of ABCB11 gene in health condition , which leads to an increased expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon4

 Activation of ABCB11 gene in obstructive cholestasis condition [6]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Obstructive cholestasis [DC10.02]

Tissue

 Liver

Related DT Changes

 up regulating

Experimental Material

 C57BL6/J mice

Detailed Description

 Bile acid receptor (NR1H4), influenced by the exogenous guggulsterone, has been reported to activate the transcription of ABCB11 gene in obstructive cholestasis condition , which leads to an increased expression of the drug transporter Bile salt export pump.

        NR1I2 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in cholestatic liver disease condition [7]

TF Protein Name

 Nuclear receptor subfamily 1 group I member 2 Transcription Factor Info

Studied Phenotype

 Cholestatic liver disease [ICD11: DB99]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 C57BL/6 mice

Detailed Description

 Nuclear receptor subfamily 1 group I member 2 (NR1I2) has been reported to activate the transcription of ABCB11 gene in cholestatic liver disease condition, which leads to an increased expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon2

 Repression of ABCB11 gene in health condition [8]

TF Protein Name

 Nuclear receptor subfamily 1 group I member 2 Transcription Factor Info

Studied Phenotype

 Heallth [ICD11: N.A]

Tissue

 Liver

Related DT Changes

 down regulating

Experimental Material

 Human hepatocytes (HH1089)

Detailed Description

 Nuclear receptor subfamily 1 group I member 2 (NR1I2), influenced by the exogenous rifampin, has been reported to repress the transcription of ABCB11 gene in health condition , which leads to a decreased expression of the drug transporter Bile salt export pump.

        NR5A2 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in hepatocellular carcinoma condition [9]

TF Protein Name

 Nuclear receptor subfamily 5 group A member 2 Transcription Factor Info

Studied Phenotype

 Hepatocellular carcinoma [ICD11: 2C12.02]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human adult hepatocellular carcinoma cells (Huh7)

Detailed Description

 Nuclear receptor subfamily 5 group A member 2 (NR5A2) has been reported to activate the transcription of ABCB11 gene in hepatocellular carcinoma condition, which leads to an increased expression of the drug transporter Bile salt export pump.

        phosphorylated NR1H4 (p.T442A) 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of ABCB11 gene in colon cancer condition [3]

TF Protein Name

 Bile acid receptor Transcription Factor Info

Studied Phenotype

 Colon cancer [ICD11: 2B90]

Tissue

 Colon

Related DT Changes

 Down regulating

Experimental Material

 Human colon adenocarcinoma cells (Caco-2)

Detailed Description

 phosphorylated Bile acid receptor (phosphorylated NR1H4 (p.T442A)) has been reported to repress the transcription of ABCB11 gene in colon cancer condition, which leads to a decreased expression of the drug transporter Bile salt export pump.

        PPARD 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Repression of ABCB11 gene in myofibroblast condition [10]

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 ABCB11 gene in myofibroblast condition, which leads to a decreased expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon2

 Repression of ABCB11 gene in breast cancer condition [11]

TF Protein Name

 Peroxisome proliferator-activated receptor delta Transcription Factor Info

Affected Drug/Substrate

 ST247, DG172

Studied Phenotype

 .

Related DT Changes

 Down regulating

Detailed Description

 Peroxisome proliferator-activated receptor delta (PPARD) has been reported to repress the transcription of ABCB11 gene in breast cancer condition, which leads to a decreased expression of the drug transporter Bile salt export pump.

        RXRA 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in hepatoblastoma condition [12]

TF Protein Name

 Retinoic acid receptor RXR-alpha Transcription Factor Info

Studied Phenotype

 Hepatoblastoma [ICD11: 2C12.01]

Tissue

 Liver

Related DT Changes

 Up regulating

Experimental Material

 Human hepatoblastoma cells (HepG2)

Detailed Description

 Retinoic acid receptor RXR-alpha (RXRA) has been reported to activate the transcription of ABCB11 gene in hepatoblastoma condition, which leads to an increased expression of the drug transporter Bile salt export pump.

      Class2.2: Other C4 zinc finger-type factors

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

        GATA1 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB11 gene in health condition [13]

TF Protein Name

 Erythroid transcription factor Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Erythroid transcription factor (GATA1) has been reported to bind to the transcription of ABCB11 gene in health condition, which leads to an affected expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon2

 Binding to ABCB11 gene in megakaryocytes condition [14]

TF Protein Name

 Erythroid transcription factor Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Erythroid transcription factor (GATA1) has been reported to bind to the transcription of ABCB11 gene in megakaryocytes condition, which leads to an affected expression of the drug transporter Bile salt export pump.

        GATA2 

Click to Show/Hide to Show 2 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB11 gene in megakaryocytes condition [14]

TF Protein Name

 Endothelial transcription factor GATA-2 Transcription Factor Info

Related DT Changes

 Direct regulating

Detailed Description

 Endothelial transcription factor GATA-2 (GATA2) has been reported to bind to the transcription of ABCB11 gene in megakaryocytes condition, which leads to an affected expression of the drug transporter Bile salt export pump.

       Transcriptional Phenomenon2

 Activation of ABCB11 gene in health condition [13]

TF Protein Name

 Endothelial transcription factor GATA-2 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Endothelial transcription factor GATA-2 (GATA2) has been reported to activate the transcription of ABCB11 gene in health condition, which leads to an increased expression of the drug transporter Bile salt export pump.

      Class2.3: C2H2 zinc finger factors

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

        SALL4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB11 gene in health condition [15]

TF Protein Name

 Sal-like protein 4 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Direct regulating

Detailed Description

 Sal-like protein 4 (SALL4) has been reported to bind to the transcription of ABCB11 gene in health condition, which leads to an affected expression of the drug transporter Bile salt export pump.

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 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Binding to ABCB11 gene in epithelial to mesenchymal transition condition [16]

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 ABCB11 gene in epithelial to mesenchymal transition condition, which leads to an affected expression of the drug transporter Bile salt export pump.

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 2 TF(s) Regulating This DT

        SMAD3 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in human embryonic stem cells (hESCs) condition [17]

TF Protein Name

 Mothers against decapentaplegic homolog 3 Transcription Factor Info

Studied Phenotype

 .

Related DT Changes

 Up regulating

Detailed Description

 Mothers against decapentaplegic homolog 3 (SMAD3) has been reported to activate the transcription of ABCB11 gene in human embryonic stem cells (hESCs) condition, which leads to an increased expression of the drug transporter Bile salt export pump.

        SMAD4 

Click to Show/Hide to Show 1 Transcriptional Phenomena      

       Transcriptional Phenomenon1

 Activation of ABCB11 gene in health condition [17]

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 ABCB11 gene in health condition, which leads to an increased expression of the drug transporter Bile salt export pump.
References
1 Nuclear factor erythroid 2-related factor 2 is a positive regulator of human bile salt export pump expression. Hepatology. 2009 Nov;50(5):1588-96.
2 Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing. Nucleic Acids Res. 2009;37(22):7498-508.
3 The membrane protein ATPase class I type 8B member 1 signals through protein kinase C zeta to activate the farnesoid X receptor. Hepatology. 2008 Dec;48(6):1896-905.
4 Hepatobiliary transport of bile acids and organic anions. J Hepatobiliary Pancreat Surg. 2002;9(4):443-7.
5 Role of nuclear bile acid receptor, FXR, in adaptive ABC transporter regulation by cholic and ursodeoxycholic acid in mouse liver, kidney and intestine. J Hepatol. 2003 Oct;39(4):480-8.
6 miR-199a-5p inhibits the expression of ABCB11 in obstructive cholestasis. J Biol Chem. 2021 Dec;297(6):101400.
7 The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J Pharmacol Exp Ther. 2005 Feb;312(2):841-8.
8 Establishing Transcriptional Signatures to Differentiate PXR-, CAR-, and AhR-Mediated Regulation of Drug Metabolism and Transport Genes in Cryopreserved Human Hepatocytes. J Pharmacol Exp Ther. 2018 May;365(2):262-271.
9 Liver receptor homolog 1 transcriptionally regulates human bile salt export pump expression. J Lipid Res. 2008 May;49(5):973-84.
10 Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor. PLoS One. 2011;6(1):e16344.
11 Inverse PPAR agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene. 2013;32(44):5241-52.
12 Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J Biol Chem. 2001 Aug 3;276(31):28857-65.
13 Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy. Mol Cell. 2009;36(4):667-81.
14 Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators. Dev Cell. 2011;20(5):597-609.
15 SALL4 is a key transcription regulator in normal human hematopoiesis. Transfusion. 2013;53(5):1037-49.
16 p63 attenuates epithelial to mesenchymal potential in an experimental prostate cell model. PLoS One. 2013;8(5):e62547.
17 Chromatin and transcriptional signatures for Nodal signaling during endoderm formation in hESCs. Dev Biol. 2011;357(2):492-504.

If you find any error in data or bug in web service, please kindly report it to Dr. Li and Dr. Fu.