Target Regulator(s) Information (Transcription Factor)
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T57392 | Target Info | |||
| Target Name | Debrisoquine 4-hydroxylase (CYP2D6) | ||||
| Synonyms | P450-DB1; Cytochrome P450-DB1; Cytochrome P450 2D6; CYPIID6; CYP2DL1 | ||||
| Target Type | Successful Target | ||||
| Gene Name | CYP2D6 | ||||
| Biochemical Class | Paired donor oxygen oxidoreductase | ||||
| UniProt ID | |||||
| The Transcription Factors (TFs) Regulating This Target | Top | ||||
|---|---|---|---|---|---|
| TF Name | Hepatocyte nuclear factor 4-alpha (HNF-4A) homodimer | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | Cys4 zinc finger of nuclear receptor type | ||||
| Family | Thyroid hormone receptor-like factors | ||||
| Subfamily | Hepatocyte nuclear factor 4 | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | Experiments in COS-7 cells showed thatHNF-4 could activate theCYP2D6promoter 30-fold. | [1] | |||
| Evidence Score (E-score) | 2 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| 2 | Electrophoretic Mobility Shift Assay | [2] | |||
| UniProt ID | |||||
| Sequence |
MRLSKTLVDMDMADYSAALDPAYTTLEFENVQVLTMGNDTSPSEGTNLNAPNSLGVSALC
AICGDRATGKHYGASSCDGCKGFFRRSVRKNHMYSCRFSRQCVVDKDKRNQCRYCRLKKC FRAGMKKEAVQNERDRISTRRSSYEDSSLPSINALLQAEVLSRQITSPVSGINGDIRAKK IASIADVCESMKEQLLVLVEWAKYIPAFCELPLDDQVALLRAHAGEHLLLGATKRSMVFK DVLLLGNDYIVPRHCPELAEMSRVSIRILDELVLPFQELQIDDNEYAYLKAIIFFDPDAK GLSDPGKIKRLRSQVQVSLEDYINDRQYDSRGRFGELLLLLPTLQSITWQMIEQIQFIKL FGMAKIDNLLQEMLLGGSPSDAPHAHHPLHPHLMQEHMGTNVIVANTMPTHLSNGQMCEW PRPRGQAATPETPQPSPPGGSGSEPYKLLPGAVATIVKPLSAIPQPTITKQEVI |
||||
| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Apolipoproteins | [+] 4 Apolipoproteins Co-regulated By This TF | + | |||
| 1 | Apolipoprotein A-I (APOA1) | Clinical trial Target | Target Info | [3] | |
| 2 | Apolipoprotein A-II (APOA2) | Literature-reported Target | Target Info | [4] | |
| 3 | Apolipoprotein B-100 (APOB) | Clinical trial Target | Target Info | [5] | |
| 4 | Apolipoprotein C-III (ApoCIII) | Clinical trial Target | Target Info | [6] | |
| Coagulation factors | [+] 1 Coagulation factors Co-regulated By This TF | + | |||
| 1 | Coagulation factor VIII (F8) | Successful Target | Target Info | [7] | |
| Hormones | [+] 1 Hormones Co-regulated By This TF | + | |||
| 1 | Erythropoietin (EPO) | Clinical trial Target | Target Info | [8] | |
| Nuclear hormone receptors | [+] 1 Nuclear hormone receptors Co-regulated By This TF | + | |||
| 1 | Hepatocyte nuclear factor 4-alpha (HNF4A) | Literature-reported Target | Target Info | [9] | |
| Oxidoreductases | [+] 2 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | Debrisoquine 4-hydroxylase (CYP2D6) | Successful Target | Target Info | [1] | |
| 2 | Heme oxygenase 1 (HMOX1) | Clinical trial Target | Target Info | [10] | |
| Peptidases | [+] 1 Peptidases Co-regulated By This TF | + | |||
| 1 | Coagulation factor IX (F9) | Successful Target | Target Info | [11] | |
| Serpin proteins | [+] 1 Serpin proteins Co-regulated By This TF | + | |||
| 1 | Angiotensinogen (AGT) | Literature-reported Target | Target Info | [12] | |
| Transferrins | [+] 1 Transferrins Co-regulated By This TF | + | |||
| 1 | Transferrin (TF) | Clinical trial Target | Target Info | [13] | |
| TF Name | COUP transcription factor (COUP-TF) homo/heterodimer | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | Cys4 zinc finger of nuclear receptor type | ||||
| Regulation Mechanism | COUP-TFI was shown to inhibitHNF4 stimulation of theCYP2D6promoter in COS-7 cells, suggesting thatCOUP-TFI could attenuate the effect ofHNF4 in HepG2 cells. | [1] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| UniProt ID | |||||
| Sequence |
MAMVVSSWRDPQDDVAGGNPGGPNPAAQAARGGGGGAGEQQQQAGSGAPHTPQTPGQPGA
PATPGTAGDKGQGPPGSGQSQQHIECVVCGDKSSGKHYGQFTCEGCKSFFKRSVRRNLTY TCRANRNCPIDQHHRNQCQYCRLKKCLKVGMRREAVQRGRMPPTQPNPGQYALTNGDPLN GHCYLSGYISLLLRAEPYPTSRYGSQCMQPNNIMGIENICELAARLLFSAVEWARNIPFF PDLQITDQVSLLRLTWSELFVLNAAQCSMPLHVAPLLAAAGLHASPMSADRVVAFMDHIR IFQEQVEKLKALHVDSAEYSCLKAIVLFTSDACGLSDAAHIESLQEKSQCALEEYVRSQY PNQPSRFGKLLLRLPSLRTVSSSVIEQLFFVRLVGKTPIETLIRDMLLSGSSFNWPYMSI QCS |
||||
| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Nuclear hormone receptors | [+] 1 Nuclear hormone receptors Co-regulated By This TF | + | |||
| 1 | Retinoic acid receptor RXR-gamma (RXRG) | Successful Target | Target Info | [14] | |
| Oxidoreductases | [+] 1 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | Debrisoquine 4-hydroxylase (CYP2D6) | Successful Target | Target Info | [1] | |
| Serpin proteins | [+] 1 Serpin proteins Co-regulated By This TF | + | |||
| 1 | Angiotensinogen (AGT) | Literature-reported Target | Target Info | [12] | |
| Transferrins | [+] 1 Transferrins Co-regulated By This TF | + | |||
| 1 | Transferrin (TF) | Clinical trial Target | Target Info | [15] | |
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Characterization of the human cytochrome P4502D6 promoter. A potential role for antagonistic interactions between members of the nuclear receptor family. J Biol Chem. 1996 Oct 11;271(41):25269-76. | ||||
| REF 2 | Contribution of hepatocyte nuclear factor-4 to down-regulation of CYP2D6 gene expression by nitric oxide. Mol Pharmacol. 2002 Jan;61(1):194-200. | ||||
| REF 3 | Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1. Mol Cell Biol. 1999 Oct;19(10):6509-22. | ||||
| REF 4 | Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, AR... J Biol Chem. 1992 Aug 5;267(22):15849-60. | ||||
| REF 5 | Identification and characterization of a 315-base pair enhancer, located more than 55 kilobases 5' of the apolipoprotein B gene, that confers expression in the intestine. J Biol Chem. 2000 Aug 25;275(34):26637-48. | ||||
| REF 6 | Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4. J Biol Chem. 1999 Nov 12;274(46):33050-6. | ||||
| REF 7 | cis-acting elements and transcription factors involved in the promoter activity of the human factor VIII gene. J Biol Chem. 1995 May 19;270(20):11828-38. | ||||
| REF 8 | The orphan receptor hepatic nuclear factor 4 functions as a transcriptional activator for tissue-specific and hypoxia-specific erythropoietin gene expression and is antagonized by EAR3/COUP-TF1. Mol Cell Biol. 1995 Apr;15(4):2135-44. | ||||
| REF 9 | Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol Cell Biol. 2001 Nov;21(21):7320-30. | ||||
| REF 10 | Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line. Biochem J. 2002 Nov 1;367(Pt 3):641-52. | ||||
| REF 11 | Disruption of a C/EBP binding site in the factor IX promoter is associated with haemophilia B. Nature. 1990 May 31;345(6274):444-6. | ||||
| REF 12 | Regulated expression of human angiotensinogen gene by hepatocyte nuclear factor 4 and chicken ovalbumin upstream promoter-transcription factor. J Biol Chem. 1999 Dec 3;274(49):34605-12. | ||||
| REF 13 | A different combination of transcription factors modulates the expression of the human transferrin promoter in liver and Sertoli cells. J Biol Chem. 1993 Nov 5;268(31):23399-408. | ||||
| REF 14 | Identification of thyroid hormone response elements in the human fatty acid synthase promoter. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12260-5. | ||||
| REF 15 | Brain-specific expression of the human transferrin gene. Similar elements govern transcription in oligodendrocytes and in a neuronal cell line. J Biol Chem. 1994 Sep 30;269(39):24504-10. | ||||
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