Contents:
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 385 | 6q21 | NR2E1 | nuclear receptor subfamily 2 group E member 1 | 2 |
| Mouse | 385 | 10 22.89 cM | Nr2e1 | nuclear receptor subfamily 2, group E, member 1 | 15 |
| Rat | - | 20 | Nr2e1 | nuclear receptor subfamily 2, group E, member 1 | |
| Previous and Unofficial Names |
| tailless homologue | TLL | frc | Mtll | XTLL | nuclear receptor subfamily 2 |
| Database Links |
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| Alphafold | Q9Y466 (Hs), Q64104 (Mm) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL1961788 (Hs) |
| Ensembl Gene | ENSG00000112333 (Hs), ENSMUSG00000019803 (Mm), ENSRNOG00000050550 (Rn) |
| Entrez Gene | 7101 (Hs), 21907 (Mm), 684085 (Rn) |
| Human Protein Atlas | ENSG00000112333 (Hs) |
| KEGG Gene | hsa:7101 (Hs), mmu:21907 (Mm), rno:684085 (Rn) |
| OMIM | 603849 (Hs) |
| Pharos | Q9Y466 (Hs) |
| RefSeq Nucleotide | NM_003269 (Hs), NM_152229 (Mm), NM_001113197 (Rn) |
| RefSeq Protein | NP_003260 (Hs), NP_689415 (Mm), NP_001106668 (Rn) |
| UniProtKB | Q9Y466 (Hs), Q64104 (Mm) |
| Wikipedia | NR2E1 (Hs) |
| Natural/Endogenous Ligands |
| Comments: Orphan |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| DNA Binding |
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| DNA Binding Comments | |||||||
| Response element for TLX is composed of the hexameric sequence AAGTCA which differs from the classical consensus sequence AGGTCA. | |||||||
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| Gfap | Mouse | Repressed | Transient transfection, EMSA, Other | TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells. | 11 |
| PAX2 | Human | Repressed | Transient transfection, EMSA, Other | The identification of Pax 2 as a TLX regulated gene is significant, because Pax2 is known to be involved in retinal development in both the human and the mouse eye. This repression by TLX is also observed in rodents and all other mammals | 15 |
| RARB | Human | Activated | Transient transfection, EMSA, Other | TLX interacts with the SET element present in the RAR β2 promoter and allows RA-dependent activation of this promoter by relieving the silencing effect of the SET element. This is also seen in other species including rodents. | 4 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| In mouse, the expression starts at day 7.5 in the head ectoderm, it is specifically localised in the developing telencephalon and in dorsal midbrain; It harbour also a dynamic expression pattern in two structures whose development requires inductive signals from the forebrain : the eye and the nose. This expression in the central nervous system persist until birth. Recently, NR2E1 was shown to be strongly expressed in the proangiogenic astrocytes, which secrete VEGF and fibronectin. NR2E1 expression by retinal astrocytes is controlled by oxygen concentration and rapidly downregulated upon contact with blood vessels. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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References
1. Faudone G, Zhubi R, Celik F, Knapp S, Chaikuad A, Heering J, Merk D. (2022) Design of a Potent TLX Agonist by Rational Fragment Fusion. J Med Chem, 65 (3): 2288-2296. [PMID:34989568]
2. Finley KD, Taylor BJ, Milstein M, McKeown M. (1997) dissatisfaction, a gene involved in sex-specific behavior and neural development of Drosophila melanogaster. Proc Natl Acad Sci USA, 94 (3): 913-8. [PMID:9023356]
3. Griffett K, Bedia-Diaz G, Hegazy L, de Vera IMS, Wanninayake US, Billon C, Koelblen T, Wilhelm ML, Burris TP. (2020) The Orphan Nuclear Receptor TLX Is a Receptor for Synthetic and Natural Retinoids. Cell Chem Biol, 27 (10): 1272-1284.e4. [PMID:32763139]
4. Kobayashi M, Yu RT, Yasuda K, Umesono K. (2000) Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX. Mol Cell Biol, 20 (23): 8731-9. [PMID:11073974]
5. Land PW, Monaghan AP. (2003) Expression of the transcription factor, tailless, is required for formation of superficial cortical layers. Cereb Cortex, 13 (9): 921-31. [PMID:12902391]
6. Land PW, Monaghan AP. (2005) Abnormal development of zinc-containing cortical circuits in the absence of the transcription factor Tailless. Brain Res Dev Brain Res, 158 (1-2): 97-101. [PMID:15950290]
7. Miyawaki T, Uemura A, Dezawa M, Yu RT, Ide C, Nishikawa S, Honda Y, Tanabe Y, Tanabe T. (2004) Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina. J Neurosci, 24 (37): 8124-34. [PMID:15371513]
8. Monaghan AP, Bock D, Gass P, Schwäger A, Wolfer DP, Lipp HP, Schütz G. (1997) Defective limbic system in mice lacking the tailless gene. Nature, 390 (6659): 515-7. [PMID:9394001]
9. Roy K, Kuznicki K, Wu Q, Sun Z, Bock D, Schutz G, Vranich N, Monaghan AP. (2004) The Tlx gene regulates the timing of neurogenesis in the cortex. J Neurosci, 24 (38): 8333-45. [PMID:15385616]
10. Roy K, Thiels E, Monaghan AP. (2002) Loss of the tailless gene affects forebrain development and emotional behavior. Physiol Behav, 77 (4-5): 595-600. [PMID:12527005]
11. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, Gage FH, Evans RM. (2004) Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature, 427 (6969): 78-83. [PMID:14702088]
12. Stenman J, Yu RT, Evans RM, Campbell K. (2003) Tlx and Pax6 co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon. Development, 130 (6): 1113-22. [PMID:12571103]
13. Uemura A, Kusuhara S, Wiegand SJ, Yu RT, Nishikawa S. (2006) Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes. J Clin Invest, 116 (2): 369-77. [PMID:16424942]
14. Young KA, Berry ML, Mahaffey CL, Saionz JR, Hawes NL, Chang B, Zheng QY, Smith RS, Bronson RT, Nelson RJ, Simpson EM. (2002) Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent. Behav Brain Res, 132 (2): 145-58. [PMID:11997145]
15. Yu RT, Chiang MY, Tanabe T, Kobayashi M, Yasuda K, Evans RM, Umesono K. (2000) The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision. Proc Natl Acad Sci USA, 97 (6): 2621-5. [PMID:10706625]
16. Yu RT, McKeown M, Evans RM, Umesono K. (1994) Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature, 370 (6488): 375-9. [PMID:8047143]
How to cite this page
2E. Tailless-like receptors: TLX. Last modified on 07/01/2022. Accessed on 31/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=615.
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