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TLX

NR2E1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNR2E1, TLL, TLX, XTLL, nuclear receptor subfamily 2 group E member 1
External IDsOMIM: 603849 MGI: 1100526 HomoloGene: 37750 GeneCards: NR2E1
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for NR2E1
Genomic location for NR2E1
Band6q21Start108,166,058 bp[1]
End108,188,809 bp[1]
RNA expression pattern
PBB GE NR2E1 207443 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001286102
NM_003269

NM_152229

RefSeq (protein)

NP_001273031
NP_003260

NP_689415

Location (UCSC)Chr 6: 108.17 – 108.19 MbChr 10: 42.56 – 42.58 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000112333 - Ensembl, May 2017
  2. ^ a b c 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. 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.
  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.
  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

External links