TLX

For other uses, see TLX (disambiguation).

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; OMA:NR2E1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6q21 Start 108,166,022 bp End 108,188,805 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10 B2|10 22.89 cM Start 42,437,959 bp End 42,459,628 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone secondary oocyte ganglionic eminence retinal pigment epithelium caudate nucleus internal globus pallidus amygdala putamen nucleus accumbens entorhinal cortex Top expressed in zygote secondary oocyte ventricular zone primary oocyte olfactory epithelium medial ganglionic eminence retinal pigment epithelium male urethra pretectal area neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sequence-specific DNA binding DNA binding DNA-binding transcription factor activity zinc ion binding DNA-binding transcription activator activity, RNA polymerase II-specific histone deacetylase binding metal ion binding steroid hormone receptor activity DNA-binding transcription repressor activity, RNA polymerase II-specific enzyme binding DNA-binding transcription factor activity, RNA polymerase II-specific protein binding Cellular component nucleoplasm 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 by RNA polymerase II 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 population proliferation cerebral cortex development social 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 by RNA polymerase II long-term 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: 42.44 – 42.46 Mb PubMed search
Wikidata
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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. TLX is a member of the nuclear receptor family of intracellular transcription factors.

Function

TLX regulates the expression of another nuclear receptor, RAR.

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

Adult neural stem cells are nuclear receptor TLX-positive and TLX expression in these cells is crucial in maintaining their undifferentiated state. 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.

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.

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.

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". 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)