Target Regulator(s) Information (Transcription Factor)
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T69146 | Target Info | |||
| Target Name | Mitochondrial uncoupling protein 3 (UCP3) | ||||
| Synonyms | UCP 3; Solute carrier family 25 member 9; SLC25A9 | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | UCP3 | ||||
| Biochemical Class | Mitochondrial carrier | ||||
| UniProt ID | |||||
| The Transcription Factors (TFs) Regulating This Target | Top | ||||
|---|---|---|---|---|---|
| TF Name | Retinoic acid receptor alpha (RAR-A) | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | Cys4 zinc finger of nuclear receptor type | ||||
| Family | Thyroid hormone receptor-like factors | ||||
| Subfamily | Retinoic acid receptors | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | Human UCP3 promoter activity is dependent on MyoD and inducible by all trans-RA. The action of all trans-RA is increased by co-transfection with RAR. | [1] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| UniProt ID | |||||
| Sequence |
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP |
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| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Apolipoproteins | [+] 2 Apolipoproteins Co-regulated By This TF | + | |||
| 1 | Apolipoprotein A-I (APOA1) | Clinical trial Target | Target Info | [2] | |
| 2 | Apolipoprotein C-III (ApoCIII) | Clinical trial Target | Target Info | [3] | |
| Growth factors | [+] 1 Growth factors Co-regulated By This TF | + | |||
| 1 | Thrombomodulin (THBD) | Discontinued Target | Target Info | [4] | |
| Hormones | [+] 1 Hormones Co-regulated By This TF | + | |||
| 1 | Insulin (INS) | Successful Target | Target Info | [5] | |
| Immunoglobulins | [+] 1 Immunoglobulins Co-regulated By This TF | + | |||
| 1 | Intercellular adhesion molecule ICAM-1 (ICAM1) | Successful Target | Target Info | [6] | |
| Mitochondrial carriers | [+] 1 Mitochondrial carriers Co-regulated By This TF | + | |||
| 1 | Mitochondrial uncoupling protein 3 (UCP3) | Clinical trial Target | Target Info | [1] | |
| Nuclear hormone receptors | [+] 3 Nuclear hormone receptors Co-regulated By This TF | + | |||
| 1 | Hepatocyte nuclear factor 4-alpha (HNF4A) | Literature-reported Target | Target Info | [7] | |
| 2 | Retinoic acid receptor beta (RARB) | Successful Target | Target Info | [8] | |
| 3 | Retinoic acid receptor gamma (RARG) | Successful Target | Target Info | [9] | |
| TF Name | Retinoid X receptor alpha (RXR-A) | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | Cys4 zinc finger of nuclear receptor type | ||||
| Family | Thyroid hormone receptor-like factors | ||||
| Subfamily | Retinoid X receptors | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | Deletion and point-mutation analysis of the hUCP3promoterled to identify a direct-repeat element with one base-pair spacing (DR1) at position -71/-59 responsible for the induction by RA of the activity of thepromoter. This DR1 element bound a nuclear protein complex from muscle cells that contain RAR and retinoid X receptor (RXR).. | [1] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [1] | |||
| UniProt ID | |||||
| Sequence |
MDTKHFLPLDFSTQVNSSLTSPTGRGSMAAPSLHPSLGPGIGSPGQLHSPISTLSSPING
MGPPFSVISSPMGPHSMSVPTTPTLGFSTGSPQLSSPMNPVSSSEDIKPPLGLNGVLKVP AHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLID KRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVERILEAEL AVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVIL LRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDM QMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLL RLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQMT |
||||
| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| Acyltransferases | [+] 1 Acyltransferases Co-regulated By This TF | + | |||
| 1 | Carnitine O-palmitoyltransferase I (CPT1B) | Successful Target | Target Info | [10] | |
| Apolipoproteins | [+] 4 Apolipoproteins Co-regulated By This TF | + | |||
| 1 | Apolipoprotein A-I (APOA1) | Clinical trial Target | Target Info | [11] | |
| 2 | Apolipoprotein A-II (APOA2) | Literature-reported Target | Target Info | [12] | |
| 3 | Apolipoprotein C-III (ApoCIII) | Clinical trial Target | Target Info | [13] | |
| 4 | Apolipoprotein E (APOE) | Clinical trial Target | Target Info | [14] | |
| Ester hydrolases | [+] 1 Ester hydrolases Co-regulated By This TF | + | |||
| 1 | Lipoprotein lipase (LPL) | Successful Target | Target Info | [15] | |
| G protein-coupled receptors | [+] 1 G protein-coupled receptors Co-regulated By This TF | + | |||
| 1 | Extracellular calcium-sensing receptor (CASR) | Successful Target | Target Info | [16] | |
| Glycoproteins | [+] 2 Glycoproteins Co-regulated By This TF | + | |||
| 1 | Cholesteryl ester transfer protein (CETP) | Clinical trial Target | Target Info | [17] | |
| 2 | Phospholipid transfer protein (PLTP) | Literature-reported Target | Target Info | [18] | |
| Kinases | [+] 1 Kinases Co-regulated By This TF | + | |||
| 1 | Epidermal growth factor receptor (EGFR) | Successful Target | Target Info | [19] | |
| Mitochondrial carriers | [+] 1 Mitochondrial carriers Co-regulated By This TF | + | |||
| 1 | Mitochondrial uncoupling protein 3 (UCP3) | Clinical trial Target | Target Info | [1] | |
| Nuclear hormone receptors | [+] 4 Nuclear hormone receptors Co-regulated By This TF | + | |||
| 1 | Hepatocyte nuclear factor 4-alpha (HNF4A) | Literature-reported Target | Target Info | [7] | |
| 2 | Retinoic acid receptor beta (RARB) | Successful Target | Target Info | [20] | |
| 3 | Retinoic acid receptor gamma (RARG) | Successful Target | Target Info | [9] | |
| 4 | Retinoic acid receptor RXR-gamma (RXRG) | Successful Target | Target Info | [21] | |
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | The human uncoupling protein-3 gene promoter requires MyoD and is induced by retinoic acid in muscle cells. FASEB J. 2000 Nov;14(14):2141-3. | ||||
| REF 2 | Differential transcriptional regulation of the apoAI gene by retinoic acid receptor homo- and heterodimers in yeast. Nucleic Acids Res. 1996 Feb 15;24(4):566-72. | ||||
| REF 3 | Binding specificity and modulation of the human ApoCIII promoter activity by heterodimers of ligand-dependent nuclear receptors. Biochemistry. 1999 Jan 19;38(3):964-75. | ||||
| REF 4 | Acceleration of thrombomodulin gene transcription by retinoic acid: retinoic acid receptors and Sp1 regulate the promoter activity through interactions with two different sequences in the 5'-flanking region of human gene. J Biol Chem. 2001 Jan 26;276(4):2440-50. | ||||
| REF 5 | Identification and characterization of a functional retinoic acid/thyroid hormone-response element upstream of the human insulin gene enhancer. Biochem J. 1995 Aug 1;309 ( Pt 3):863-70. | ||||
| REF 6 | Heterodimeric retinoic acid receptor-beta and retinoid X receptor-alpha complexes stimulate expression of the intercellular adhesion molecule-1 gene. Cell Growth Differ. 1995 May;6(5):515-21. | ||||
| REF 7 | Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol Cell Biol. 2001 Nov;21(21):7320-30. | ||||
| REF 8 | Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature. 1990 Jan 11;343(6254):177-80. | ||||
| REF 9 | RAR gamma 2 expression is regulated through a retinoic acid response element embedded in Sp1 sites. Mol Cell Biol. 1992 Jul;12(7):2976-85. | ||||
| REF 10 | Co-regulation of tissue-specific alternative human carnitine palmitoyltransferase Ibeta gene promoters by fatty acid enzyme substrate. J Biol Chem. 1998 Dec 4;273(49):32901-9. | ||||
| REF 11 | Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element. J Clin Invest. 2002 Apr;109(7):961-71. | ||||
| REF 12 | Retinoids increase human apolipoprotein A-11 expression through activation of the retinoid X receptor but not the retinoic acid receptor. Mol Cell Biol. 1996 Jul;16(7):3350-60. | ||||
| REF 13 | Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III. J Biol Chem. 1995 Jun 2;270(22):13470-5. | ||||
| REF 14 | LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):507-12. | ||||
| REF 15 | PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996 Oct 1;15(19):5336-48. | ||||
| REF 16 | Human calcium-sensing receptor gene. Vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem. 2002 Aug 16;277(33):30337-50. | ||||
| REF 17 | The orphan nuclear receptor LRH-1 potentiates the sterol-mediated induction of the human CETP gene by liver X receptor. J Biol Chem. 2001 Jul 6;276(27):24767-73. | ||||
| REF 18 | The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. J Biol Chem. 2000 Dec 15;275(50):39313-7. | ||||
| REF 19 | T3 receptor suppression of Sp1-dependent transcription from the epidermal growth factor receptor promoter via overlapping DNA-binding sites. J Biol Chem. 1993 Jul 25;268(21):16065-73. | ||||
| REF 20 | Vitamin D represses retinoic acid-dependent transactivation of the retinoic acid receptor-beta2 promoter: the AF-2 domain of the vitamin D receptor is required for transrepression. Endocrinology. 1999 Jun;140(6):2898-907. | ||||
| REF 21 | 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. | ||||
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