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Gene Review

TLX2  -  T-cell leukemia homeobox 2

Homo sapiens

Synonyms: Enx, HOX11L1, Homeobox protein Hox-11L1, NCX, Neural crest homeobox protein, ...
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Disease relevance of TLX2


Psychiatry related information on TLX2


High impact information on TLX2

  • The plasma membrane Na+/Ca2+ exchanger (NCX) is almost certainly the major Ca2+ extrusion mechanism in cardiac myocytes [7].
  • Specific point mutations in either domain largely allow the interchange of their functionality and uncover the mechanism underlying Ca2+ sensing in NCX [7].
  • Effects of a nitroxybutylester derivative of aspirin (NCX 4215) on platelet aggregation and prostanoid synthesis were compared to the effects of aspirin [8].
  • NCX 4215 did not alter systemic arterial blood pressure when administered intravenously to the rat [8].
  • The sodium-calcium exchanger (NCX) is a critical mediator of calcium homeostasis [9].

Chemical compound and disease context of TLX2


Biological context of TLX2

  • Such interaction was also confirmed in vivo by means of chromatin immunoprecipitation assay and, in addition, up-regulation of endogenous TLX2 mRNA level was demonstrated following PHOX2B over-expression, by quantitative real-time PCR [1].
  • Taken together, these results support the PHOX2B-TLX2 promoter interaction, suggesting a physiological role in the transcription-factor cascade underlying the differentiation of neuronal lineages of the ANS during human embryogenesis [1].
  • After characterizing a sequence displaying enhancer property in its 5' flanking region, we confirmed the functional link between the human PHOX2B and TLX2 genes [1].
  • The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells [1].
  • Gel shift assays performed with oligonucleotides spanning this promoter sequence showed a change of the SP1 interaction with its binding sites, consequent to transfection with HOX11L1 [15].

Anatomical context of TLX2


Associations of TLX2 with chemical compounds

  • NCX 4215 was approximately seven times more potent than aspirin as an inhibitor of thrombin-induced human platelet aggregation in vitro, but did not inhibit platelet thromboxane synthesis or gastric prostaglandin synthesis [8].
  • In the present study, employing two unrelated Na+/Ca2+ exchange inhibitors, 3',4'-dichlorobenzamil (DCB) and bepridil, we investigated the role of NCX in platelet activation induced by various agonists in detail [17].
  • Biochemical and ultrastructural analyses showed that NCX inhibitors, particularly DCB, made platelets "thrombasthenic". These findings suggest that the NCX is involved in the common steps of inside-out signaling through integrin IIbbeta3 [17].
  • Studies in cell lines and animal models have shown that flurbiprofen racemate, its R-enantiomer and its nitric oxide (NO)-releasing derivatives, HCT 1026 and NCX 2216, are effective on AD amyloid pathology [18].
  • In hypertrophic neonatal rat cardiomyocytes subjected to chronic phenylephrine treatment, we observed a marked depression of NCX activity measured as the rate of Na(+)(i)-dependent (45)Ca(2+) uptake or the rate of Na(+)(o)-dependent (45)Ca(2+) efflux [4].

Other interactions of TLX2


Analytical, diagnostic and therapeutic context of TLX2

  • Aspirin (10-120 mg/kg) caused extensive hemorrhagic erosion formation in the stomach of the rat within 3 h of oral administration, while NCX 4215 did not produce significant damage at doses of up to 300 mg/kg, nor when given daily for two weeks at 166 mg/kg [8].
  • NCX mRNA levels were studied using RNase Protection Assay (RPA) and NCX protein levels were assessed by Western blot [20].
  • In reverse transcription polymerase chain reaction (RT-PCR) analysis, EBER-1 mRNAwas expressed in 74% (23/31) of ICC, 83% (19/23) of CIN, 37% (13/35) of NCX [21].
  • The NCX formed between dynorphin 1-7 and Mini Gastrin I is used as a model system for comparison to previous MALDI experiments (Woods, A. S.; Huestis, M. A. J. Am. Soc. Mass Spectrom. 2001, 12, 88-96) [22].
  • Surface plasmon resonance assays in NF MPs allowed us to demonstrate direct interaction between the NCX and caveolin-3 and immobilized annexin A5 [23].


  1. The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells. Borghini, S., Bachetti, T., Fava, M., Di Duca, M., Cargnin, F., Fornasari, D., Ravazzolo, R., Ceccherini, I. Biochem. J. (2006) [Pubmed]
  2. HOX11L1, a gene involved in peripheral nervous system development, maps to human chromosome 2p13.1-->p12 and mouse chromosome 6C3-D1. Puliti, A., Cinti, R., Betsos, N., Romeo, G., Ceccherini, I. Cytogenet. Cell Genet. (1999) [Pubmed]
  3. HOX11L2 expression defines a clinical subtype of pediatric T-ALL associated with poor prognosis. Ballerini, P., Blaise, A., Busson-Le Coniat, M., Su, X.Y., Zucman-Rossi, J., Adam, M., van den Akker, J., Perot, C., Pellegrino, B., Landman-Parker, J., Douay, L., Berger, R., Bernard, O.A. Blood (2002) [Pubmed]
  4. Calcineurin inhibits Na+/Ca2+ exchange in phenylephrine-treated hypertrophic cardiomyocytes. Katanosaka, Y., Iwata, Y., Kobayashi, Y., Shibasaki, F., Wakabayashi, S., Shigekawa, M. J. Biol. Chem. (2005) [Pubmed]
  5. Dynamic regulation of microglial functions by the non-steroidal anti-inflammatory drug NCX 2216: implications for chronic treatments of neurodegenerative diseases. Bernardo, A., Gasparini, L., Ongini, E., Minghetti, L. Neurobiol. Dis. (2006) [Pubmed]
  6. In vitro effects of a novel class of nitric oxide (NO) donating compounds on isolated human erectile tissue. Seidler, M., Uckert, S., Waldkirch, E., Stief, C.G., Oelke, M., Tsikas, D., Sohn, M., Jonas, U. Eur. Urol. (2002) [Pubmed]
  7. Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors. Hilge, M., Aelen, J., Vuister, G.W. Mol. Cell (2006) [Pubmed]
  8. Anti-thrombotic effects of a nitric oxide-releasing, gastric-sparing aspirin derivative. Wallace, J.L., McKnight, W., Del Soldato, P., Baydoun, A.R., Cirino, G. J. Clin. Invest. (1995) [Pubmed]
  9. Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs. Riedel, M.J., Baczk??, I., Searle, G.J., Webster, N., Fercho, M., Jones, L., Lang, J., Lytton, J., Dyck, J.R., Light, P.E. EMBO J. (2006) [Pubmed]
  10. Inhibitory effect of NO-releasing ciprofloxacin (NCX 976) on Mycobacterium tuberculosis survival. Ciccone, R., Mariani, F., Cavone, A., Persichini, T., Venturini, G., Ongini, E., Colizzi, V., Colasanti, M. Antimicrob. Agents Chemother. (2003) [Pubmed]
  11. Loss of beta-adrenoceptor response in myocytes overexpressing the Na+/Ca(2+)-exchanger. Sato, M., Gong, H., Terracciano, C.M., Ranu, H., Harding, S.E. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  12. Alkalosis stimulates endothelial nitric oxide synthase in cultured human pulmonary arterial endothelial cells. Mizuno, S., Demura, Y., Ameshima, S., Okamura, S., Miyamori, I., Ishizaki, T. Am. J. Physiol. Lung Cell Mol. Physiol. (2002) [Pubmed]
  13. Amiloride kills malignant glioma cells independent of its inhibition of the sodium-hydrogen exchanger. Hegde, M., Roscoe, J., Cala, P., Gorin, F. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  14. Salt intake and depletion increase circulating levels of endogenous ouabain in normal men. Manunta, P., Hamilton, B.P., Hamlyn, J.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  15. An in vitro approach to test the possible role of candidate factors in the transcriptional regulation of the RET proto-oncogene. Bachetti, T., Borghini, S., Ravazzolo, R., Ceccherini, I. Gene Expr. (2005) [Pubmed]
  16. Association of the TLX-2 homeodomain and 14-3-3eta signaling proteins. Tang, S.J., Suen, T.C., McInnes, R.R., Buchwald, M. J. Biol. Chem. (1998) [Pubmed]
  17. Involvement of Na+/Ca2+ exchanger in inside-out signaling through the platelet integrin IIbbeta3. Shiraga, M., Tomiyama, Y., Honda, S., Suzuki, H., Kosugi, S., Tadokoro, S., Kanakura, Y., Tanoue, K., Kurata, Y., Matsuzawa, Y. Blood (1998) [Pubmed]
  18. Activity of flurbiprofen and chemically related anti-inflammatory drugs in models of Alzheimer's disease. Gasparini, L., Ongini, E., Wilcock, D., Morgan, D. Brain Res. Brain Res. Rev. (2005) [Pubmed]
  19. DQX1, an RNA-dependent ATPase homolog with a novel DEAQ box: expression pattern and genomic sequence comparison of the human and mouse genes. Ji, W., Chen, F., Do, T., Do, A., Roe, B.A., Meisler, M.H. Mamm. Genome (2001) [Pubmed]
  20. Gene expression of Na+/Ca2+ exchanger during development in human heart. Qu, Y., Ghatpande, A., el-Sherif, N., Boutjdir, M. Cardiovasc. Res. (2000) [Pubmed]
  21. Epstein-Barr virus (EBV) genes expression in cervical intraepithelial neoplasia and invasive cervical cancer: a comparative study with human papillomavirus (HPV) infection. Sasagawa, T., Shimakage, M., Nakamura, M., Sakaike, J., Ishikawa, H., Inoue, M. Hum. Pathol. (2000) [Pubmed]
  22. A study of peptide-peptide interactions using MALDI ion mobility o-TOF and ESI mass spectrometry. Woods, A.S., Koomen, J.M., Ruotolo, B.T., Gillig, K.J., Russel, D.H., Fuhrer, K., Gonin, M., Egan, T.F., Schultz, J.A. J. Am. Soc. Mass Spectrom. (2002) [Pubmed]
  23. Association of annexin A5 with Na+/Ca2+ exchanger and caveolin-3 in non-failing and failing human heart. Camors, E., Charue, D., Trouvé, P., Monceau, V., Loyer, X., Russo-Marie, F., Charlemagne, D. J. Mol. Cell. Cardiol. (2006) [Pubmed]
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