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Gene Review

NR2E1  -  nuclear receptor subfamily 2, group E,...

Homo sapiens

Synonyms: Nuclear receptor TLX, Nuclear receptor subfamily 2 group E member 1, Protein tailless homolog, TLL, TLX, ...
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Disease relevance of NR2E1

  • Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci [1].
  • In fierce mutants carrying human NR2E1, structural brain defects were eliminated and eye abnormalities ameliorated [2].
  • 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 [3].
  • It is proposed that such TLX alloantigens are central in establishing maternal recognition and protection of the blastocyst, and that lack of recognition results in implantation failure and spontaneous abortion [4].
  • The corresponding proliferative responses to BCG were 19,908 cpm in the TLL group and 7908 in the ULL group [5].

High impact information on NR2E1

  • Antisera to human syncytiotrophoblast microvillous cell surface membranes from different placentas are cytotoxic for lymphocytes from some people but not others, demonstrating the presence of allotypic trophoblast-lymphocyte cross-reactive (TLX) antigens [4].
  • Exploratory principal components factor analysis, performed on limited data consisting of 300 cytotoxic reactions produced by ten separate trophoblast antisera on a panel of lymphocytes from 30 random donors, suggested the presence of three distinct TLX antigen groupings [4].
  • Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1 [6].
  • Ectopic expression of TLX in fibroblasts resulted in increased sensitivity to RA induction, an effect that is conserved between chick and mammals [7].
  • We have identified a cis element, the silencing element relieved by TLX (SET), within the RARbeta2 promoter region which confers TLX- and RA-dependent transactivation [7].

Biological context of NR2E1

  • A high degree of conservation across NR2E1 combined with a lack of interspersed repeats suggests that an array of regulatory elements embedded within the gene is required for proper gene expression [1].
  • Because no artificial promoter was used to drive transgene expression, promoter and regulatory elements within the human NR2E1 clone are functional in mouse [2].
  • Heterologous sera raised to human trophoblast (TLX antisera) have been shown to recognize peripheral blood lymphocytes (PBL); in unrelated studies noncytotoxic Fc receptors blocking B lymphocyte antibodies have been found in the sera of women during normal pregnancies [8].
  • Evidence id presented for the presence of trophoblast-lymphocyte cross-reaction (TLX) cell surface antigens [9].
  • 2. Allotypic seminal plasma TLX antigens may provide the antigenic stimuli for persistent maternal humoral immunity [10].

Anatomical context of NR2E1


Associations of NR2E1 with chemical compounds


Regulatory relationships of NR2E1

  • TLX is predominately expressed in the brain and maps to RMD-2 at 6q21 between DNA markers FYN and D6S447, in a YAC clone that also contains marker D6S246 [3].

Analytical, diagnostic and therapeutic context of NR2E1

  • Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans [13].
  • The most potent antigen on the placenta is a class I molecule different from the classical transplantation antigens: Pa in the rat and TLX in the human [15].
  • Xenogeneic anti-TLX sera were studied with the use of enzyme-linked-immunosorbent (ELISA) and immunochemical assays to determine the TLX status of seminal plasma [10].
  • Well-defined monoclonal antibodies directed against HLA class I and class II molecules as well as beta 2-microglobulin and a TLX molecule were used in a standard indirect immunofluorescence test and some immunogold techniques at the electron microscopic level [16].
  • As additional therapy, stent insertion and peripheral (Aa. poplitea Tll/tibial) angioplasty was performed (4 patients per group) [17].


  1. Novel vertebrate genes and putative regulatory elements identified at kidney disease and NR2E1/fierce loci. Abrahams, B.S., Mak, G.M., Berry, M.L., Palmquist, D.L., Saionz, J.R., Tay, A., Tan, Y.H., Brenner, S., Simpson, E.M., Venkatesh, B. Genomics (2002) [Pubmed]
  2. Pathological aggression in "fierce" mice corrected by human nuclear receptor 2E1. Abrahams, B.S., Kwok, M.C., Trinh, E., Budaghzadeh, S., Hossain, S.M., Simpson, E.M. J. Neurosci. (2005) [Pubmed]
  3. 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. Jackson, A., Panayiotidis, P., Foroni, L. Genomics (1998) [Pubmed]
  4. Human trophoblast-lymphocyte cross-reactive (TLX) antigens define a new alloantigen system. McIntyre, J.A., Faulk, W.P., Verhulst, S.J., Colliver, J.A. Science (1983) [Pubmed]
  5. Mycobacterium leprae reactive T cell clones from lepromatous leprosy patients after prolonged dapsone chemotherapy. Gill, H.K., Ridley, D.S., Ganesan, J., Mustafa, A.S., Rees, R.J., Godal, T. Leprosy review. (1990) [Pubmed]
  6. Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1. Zhang, C.L., Zou, Y., Yu, R.T., Gage, F.H., Evans, R.M. Genes Dev. (2006) [Pubmed]
  7. Cell-type-specific regulation of the retinoic acid receptor mediated by the orphan nuclear receptor TLX. Kobayashi, M., Yu, R.T., Yasuda, K., Umesono, K. Mol. Cell. Biol. (2000) [Pubmed]
  8. Differential expression of trophoblast lymphocyte cross-reactive (TLX) antigens on T and B lymphocytes. MacLeod, A.M., Catto, G.R., Stewart, K.N., Mather, A.J., Mason, R.J., Power, D.A., McIntyre, J.A. American journal of reproductive immunology and microbiology : AJRIM. (1986) [Pubmed]
  9. Allotypic trophoblast-lymphocyte cross-reactive (TLX) cell surface antigens. McIntyre, J.A., Faulk, W.P. Hum. Immunol. (1982) [Pubmed]
  10. Trophoblast antigens in human seminal plasma. Kajino, T., Torry, D.S., McIntyre, J.A., Faulk, W.P. American journal of reproductive immunology and microbiology : AJRIM. (1988) [Pubmed]
  11. Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies. Nishimura, M., Naito, S., Yokoi, T. Drug Metab. Pharmacokinet. (2004) [Pubmed]
  12. Isolation and identification of trophoblast lymphocyte cross-reactive (TLX) antigens from human lymphocytes. Kim, I.C. J. Biol. Chem. (1989) [Pubmed]
  13. Relation between MR abnormalities and patterns of cognitive impairment in multiple sclerosis. Rovaris, M., Filippi, M., Falautano, M., Minicucci, L., Rocca, M.A., Martinelli, V., Comi, G. Neurology (1998) [Pubmed]
  14. Seminal vesicles: a source of trophoblast lymphocyte cross-reactive antigen. Thaler, C.J., Critser, J.K., McIntyre, J.A., Faulk, W.P. Fertil. Steril. (1989) [Pubmed]
  15. Immunological and genetic factors influencing pregnancy and development. Gill, T.J. American journal of reproductive immunology and microbiology : AJRIM. (1986) [Pubmed]
  16. HLA and TLX antigen expression on the human oocyte, zona pellucida and granulosa cells. Dohr, G. Hum. Reprod. (1987) [Pubmed]
  17. Intra-arterial Doppler flowmetry in the superficial femoral artery following angioplasty. Beyer-Enke, S.A., Adamus, R., Loose, R., Zeitler, E. European radiology. (2000) [Pubmed]
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