Target Regulator(s) Information (Transcription Factor)
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T82841 | Target Info | |||
| Target Name | Insulin (INS) | ||||
| Synonyms | Insulin | ||||
| Target Type | Successful Target | ||||
| Gene Name | INS | ||||
| UniProt ID | |||||
| The Transcription Factors (TFs) Regulating This Target | Top | ||||
|---|---|---|---|---|---|
| TF Name | Steroidogenic factor 1 (STF1) | ||||
| Classification | Superclass | Zinc-coordinating DNA-binding domains | |||
| Class | Cys4 zinc finger of nuclear receptor type | ||||
| Regulation Type | Increase | ||||
| Regulation Mechanism | Decreased STF1 binding is associated with decreased INS promoter activity in HIT cells chronically cultured in a supraphysiological glucose concentration. | [1] | |||
| Evidence Score (E-score) | 2 | + | |||
| 1 | Chloramphenicol Acetyltransferase Assay, Electrophoretic Mobility Shift Assay | [1] | |||
| 2 | Electrophoretic Mobility Shift Assay | [3] | |||
| UniProt ID | |||||
| Sequence |
MDYSYDEDLDELCPVCGDKVSGYHYGLLTCESCKGFFKRTVQNNKHYTCTESQSCKIDKT
QRKRCPFCRFQKCLTVGMRLEAVRADRMRGGRNKFGPMYKRDRALKQQKKAQIRANGFKL ETGPPMGVPPPPPPAPDYVLPPSLHGPEPKGLAAGPPAGPLGDFGAPALPMAVPGAHGPL AGYLYPAFPGRAIKSEYPEPYASPPQPGLPYGYPEPFSGGPNVPELILQLLQLEPDEDQV RARILGCLQEPTKSRPDQPAAFGLLCRMADQTFISIVDWARRCMVFKELEVADQMTLLQN CWSELLVFDHIYRQVQHGKEGSILLVTGQEVELTTVATQAGSLLHSLVLRAQELVLQLLA LQLDRQEFVCLKFIILFSLDLKFLNNHILVKDAQEKANAALLDYTLCHYPHCGDKFQQLL LCLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEMLQAKQT |
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| The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes | |||||
| G protein-coupled receptors | [+] 1 G protein-coupled receptors Co-regulated By This TF | + | |||
| 1 | Melanocortin receptor 2 (MC2R) | Successful Target | Target Info | [4] | |
| Hormones | [+] 1 Hormones Co-regulated By This TF | + | |||
| 1 | Insulin (INS) | Successful Target | Target Info | [1] | |
| Oxidoreductases | [+] 1 Oxidoreductases Co-regulated By This TF | + | |||
| 1 | Cholesterol desmolase (CYP11A1) | Successful Target | Target Info | [5] | |
| 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 | The INS expressing cell line contains thyroid hormone and RARs at least, and that these receptors are able to recognize the Ink sequence. Three copies of the Ink sequence were placed upstream of the thymidine kinase promoter and firefly luciferase reporter gene. | [2] | |||
| Evidence Score (E-score) | 1 | + | |||
| 1 | Electrophoretic Mobility Shift Assay | [2] | |||
| UniProt ID | |||||
| Sequence |
MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPAT
IETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNM VYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTL TPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTV EFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNA GFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALK VYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGL DTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP |
||||
| 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 | [6] | |
| 2 | Apolipoprotein C-III (ApoCIII) | Clinical trial Target | Target Info | [7] | |
| Growth factors | [+] 1 Growth factors Co-regulated By This TF | + | |||
| 1 | Thrombomodulin (THBD) | Discontinued Target | Target Info | [8] | |
| Hormones | [+] 1 Hormones Co-regulated By This TF | + | |||
| 1 | Insulin (INS) | Successful Target | Target Info | [2] | |
| Immunoglobulins | [+] 1 Immunoglobulins Co-regulated By This TF | + | |||
| 1 | Intercellular adhesion molecule ICAM-1 (ICAM1) | Successful Target | Target Info | [9] | |
| Mitochondrial carriers | [+] 1 Mitochondrial carriers Co-regulated By This TF | + | |||
| 1 | Mitochondrial uncoupling protein 3 (UCP3) | Clinical trial Target | Target Info | [10] | |
| Nuclear hormone receptors | [+] 3 Nuclear hormone receptors Co-regulated By This TF | + | |||
| 1 | Hepatocyte nuclear factor 4-alpha (HNF4A) | Literature-reported Target | Target Info | [11] | |
| 2 | Retinoic acid receptor beta (RARB) | Successful Target | Target Info | [12] | |
| 3 | Retinoic acid receptor gamma (RARG) | Successful Target | Target Info | [13] | |
| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Glucose rapidly and reversibly decreases INS-1 cell insulin gene transcription via decrements in STF-1 and C1 activator transcription factor activity. Mol Endocrinol. 1998 Feb;12(2):207-19. | ||||
| REF 2 | 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 3 | Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10465-9. | ||||
| REF 4 | Three steroidogenic factor-1 binding elements are required for constitutive and cAMP-regulated expression of the human adrenocorticotropin receptor gene. Biochem Biophys Res Commun. 1999 Feb 5;255(1):28-33. | ||||
| REF 5 | Regulatory mechanisms of cAMP-dependent and cell-specific expression of human steroidogenic cytochrome P450scc (CYP11A1) gene. Eur J Biochem. 1994 Jun 15;222(3):825-34. | ||||
| REF 6 | 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 7 | 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 8 | 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 9 | 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 10 | 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 11 | Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression. Mol Cell Biol. 2001 Nov;21(21):7320-30. | ||||
| REF 12 | Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature. 1990 Jan 11;343(6254):177-80. | ||||
| REF 13 | 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. | ||||
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