TLX

Nuclear receptor TLX (homologue of the Drosophila tailless gene) also known as NR2E1 (Nuclear receptor subfamily 2 group E member 1) is a protein that in humans is encoded by the NR2E1 gene.[5] TLX is a member of the nuclear receptor family of intracellular transcription factors.

NR2E1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4XAJ
Identifiers
Aliases	NR2E1, TLL, TLX, XTLL, nuclear receptor subfamily 2 group E member 1
External IDs	OMIM: 603849 MGI: 1100526 HomoloGene: 37750 GeneCards: NR2E1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6q21 Start 108,166,058 bp[1] End 108,188,809 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B2|10 22.89 cM Start 42,561,963 bp[2] End 42,583,632 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • sequence-specific DNA binding • DNA binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • zinc ion binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • histone deacetylase binding • metal ion binding • steroid hormone receptor activity • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific • enzyme binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • GO:0001948 protein binding Cellular component • nucleoplasm • cell nucleus Biological process • glial cell migration • cell fate commitment • negative regulation of astrocyte differentiation • regulation of transcription, DNA-templated • negative regulation of neuron differentiation • somatic stem cell population maintenance • dentate gyrus development • negative regulation of neural precursor cell proliferation • regulation of cellular component organization • extracellular matrix organization • negative regulation of apoptotic process • negative regulation of transcription from RNA polymerase II promoter • behavioral fear response • regulation of timing of neuron differentiation • transcription, DNA-templated • nervous system development • positive regulation of angiogenesis • anterior commissure morphogenesis • regulation of dendrite morphogenesis • positive regulation of neural precursor cell proliferation • multicellular organism development • brain development • positive regulation of cell cycle • amygdala development • retina development in camera-type eye • forebrain generation of neurons • layer formation in cerebral cortex • positive regulation of cell proliferation • cerebral cortex development • social organism behavior • cerebral cortex neuron differentiation • regulation of cell migration involved in sprouting angiogenesis • camera-type eye development • olfactory bulb development • transcription initiation from RNA polymerase II promoter • positive regulation of stem cell proliferation • aggressive behavior • visual perception • steroid hormone mediated signaling pathway • positive regulation of transcription from RNA polymerase II promoter • long-term synaptic potentiation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7101	21907
Ensembl	ENSG00000112333	ENSMUSG00000019803
UniProt	Q9Y466	Q64104
RefSeq (mRNA)	NM_001286102 NM_003269	NM_152229
RefSeq (protein)	NP_001273031 NP_003260	NP_689415
Location (UCSC)	Chr 6: 108.17 – 108.19 Mb	Chr 10: 42.56 – 42.58 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

TLX regulates the expression of another nuclear receptor, RAR.[6]

TLX also is essential for normal brain-eye coordination and appears to play a role in control of aggressive behavior.[7]

Adult neural stem cells are nuclear receptor TLX-positive and TLX expression in these cells is crucial in maintaining their undifferentiated state.[8] Furthermore, TLX regulates adult neural stem cell proliferation. Removal of TLX from the adult mouse brain resulted in a reduction of stem cell proliferation and spatial learning.[9]

Tlx-positive cells of the subventricular zone of adult mouse brain are self-renewing stem cells. Mutation of the Tlx gene in adult mouse brain leads to complete loss of neurogenesis in the subventricular zone. Tlx is also required for transition from radial glial cells to astrocyte-like neural stem cells.[10]

Ligands

TLX belongs to a small family of NRs that lack two helices in the ligand-binding domain, forming an enlarged binding pocket. Three compounds, termed ccrp1–3 (famprofazone, 1-(1,5-dimethylpyrazole-3-carbonyl)-4-(diphenylmethyl)piperazine, dydrogesterone), have been discovered in high-throughput screening that enhance TLX's ability of transcription repression with high potency.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000112333 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019803 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Jackson A, Panayiotidis P, Foroni L (May 1998). "The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21". Genomics. 50 (1): 34–43. doi:10.1006/geno.1998.5270. PMID 9628820.
6. Kobayashi M, Yu RT, Yasuda K, Umesono K (December 2000). "Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX". Molecular and Cellular Biology. 20 (23): 8731–9. doi:10.1128/MCB.20.23.8731-8739.2000. PMC 86495. PMID 11073974.
7. Abrahams BS, Kwok MC, Trinh E, Budaghzadeh S, Hossain SM, Simpson EM (July 2005). "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1" (PDF). The Journal of Neuroscience. 25 (27): 6263–70. doi:10.1523/JNEUROSCI.4757-04.2005. PMC 6725287. PMID 16000615.
8. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, et al. (January 2004). "Expression and function of orphan nuclear receptor TLX in adult neural stem cells". Nature. 427 (6969): 78–83. Bibcode:2004Natur.427...78S. doi:10.1038/nature02211. PMID 14702088. S2CID 6495861.
9. Zhang CL, Zou Y, He W, Gage FH, Evans RM (February 2008). "A role for adult TLX-positive neural stem cells in learning and behaviour". Nature. 451 (7181): 1004–7. Bibcode:2008Natur.451.1004Z. doi:10.1038/nature06562. PMID 18235445. S2CID 14445703.
10. Liu HK, Belz T, Bock D, Takacs A, Wu H, Lichter P, et al. (September 2008). "The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone". Genes & Development. 22 (18): 2473–8. doi:10.1101/gad.479308. PMC 2546695. PMID 18794344.
11. Benod C, Villagomez R, Filgueira CS, Hwang PK, Leonard PG, Poncet-Montange G, et al. (2014). "The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable". PLOS ONE. 9 (6): e99440. Bibcode:2014PLoSO...999440B. doi:10.1371/journal.pone.0099440. PMC 4060991. PMID 24936658.

Further reading

• Yu RT, McKeown M, Evans RM, Umesono K (August 1994). "Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx". Nature. 370 (6488): 375–9. Bibcode:1994Natur.370..375Y. doi:10.1038/370375a0. PMID 8047143. S2CID 4326071.
• Kobayashi M, Yu RT, Yasuda K, Umesono K (December 2000). "Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX". Molecular and Cellular Biology. 20 (23): 8731–9. doi:10.1128/MCB.20.23.8731-8739.2000. PMC 86495. PMID 11073974.
• Abrahams BS, Mak GM, Berry ML, Palmquist DL, Saionz JR, Tay A, et al. (July 2002). "Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci". Genomics. 80 (1): 45–53. doi:10.1006/geno.2002.6795. PMID 12079282.
• Abrahams BS, Kwok MC, Trinh E, Budaghzadeh S, Hossain SM, Simpson EM (July 2005). "Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1" (PDF). The Journal of Neuroscience. 25 (27): 6263–70. doi:10.1523/JNEUROSCI.4757-04.2005. PMC 6725287. PMID 16000615.
• Kumar RA, Leach S, Bonaguro R, Chen J, Yokom DW, Abrahams BS, et al. (August 2007). "Mutation and evolutionary analyses identify NR2E1-candidate-regulatory mutations in humans with severe cortical malformations". Genes, Brain, and Behavior. 6 (6): 503–16. doi:10.1111/j.1601-183X.2006.00277.x. PMC 2040186. PMID 17054721.
• Kumar RA, Everman DB, Morgan CT, Slavotinek A, Schwartz CE, Simpson EM (July 2007). "Absence of mutations in NR2E1 and SNX3 in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes". BMC Medical Genetics. 8: 48. doi:10.1186/1471-2350-8-48. PMC 1950490. PMID 17655765.
• Sun G, Yu RT, Evans RM, Shi Y (September 2007). "Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation". Proceedings of the National Academy of Sciences of the United States of America. 104 (39): 15282–7. Bibcode:2007PNAS..10415282S. doi:10.1073/pnas.0704089104. PMC 2000559. PMID 17873065.

External links

• NR2E1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)