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Gene Review

LBX1  -  ladybird homeobox 1

Homo sapiens

Synonyms: HPX-6, HPX6, LBX1H, Ladybird homeobox protein homolog 1, Transcription factor LBX1, ...
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Disease relevance of LBX1


Psychiatry related information on LBX1


High impact information on LBX1


Chemical compound and disease context of LBX1


Biological context of LBX1

  • PURPOSE: A previous study demonstrated that CTCF (CCCTC binding factor) regulates homeobox Pax6 gene expression in early embryonic stages and plays a dominant role in eye development [19].
  • Altogether, our results strongly suggest the absolute requirement for cooperative events in association with homeobox gene up-regulation to induce T-cell leukemogenesis [20].
  • Deletions of 2q14 that include the homeobox engrailed 1 (EN1) transcription factor are compatible with a normal phenotype [21].
  • The identification of five new genes using a subclass-specific 5' primer, designed from the engrailed and Xanf1 sequences, suggests that there still remain several uncharacterized HB genes in the human genome [22].
  • Within the serial array of vertebrate homeobox genes in the Hox complexes, it is possible to define a subgroup that is structurally homologous to the Drosophila homeotic gene Deformed (Dfd) [23].

Anatomical context of LBX1


Associations of LBX1 with chemical compounds


Physical interactions of LBX1

  • Here we show for the first time that SIRT2 interacts with the homeobox transcription factor, HOXA10, which was identified in a two-hybrid screen [33].
  • Previously, we have demonstrated that GBX genes, a homeobox-containing human family of DNA-binding transcription factors consisting of GBX1 and GBX2, are overexpressed in a panel of human prostatic cancer cell lines (ie., TSU-pr1, PC3, DU145, and LNCaP) compared to normal prostate [34].
  • Recently, inappropriate activation of the intestine-specific transcription factor like the homeobox gene complex CDX1 and CDX2 are found to be an important contributing factor in the induction of intestinal metaplasia in the stomach [35].
  • The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes [36].
  • Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis [37].

Enzymatic interactions of LBX1

  • We show that HOXC13, but not a homeobox-deleted HOXC13, strongly activated the promoters of the genes, with the respective proximal promoter regions being sufficient for optimal activation [38].
  • Our studies of human CFTR transcription focus on identifying transcription factors bound to an inverted CCAAT consensus or "Y-box element." The human homeodomain CCAAT displacement protein/cut homolog (CDP/cut) can bind to the Y-box element through a cut repeat and homeobox [39].

Regulatory relationships of LBX1

  • This is the first report of a homeobox gene being specifically regulated by PBX2 and the second report of a vertebrate homeobox target gene of a PBX protein [40].
  • CDX2 is known to regulate class I homeobox genes and its expression in hematopoietic cells may critically alter the balance between differentiation and proliferation [41].
  • These results suggest that MLL fusion proteins impose a reversible block on myeloid differentiation through aberrant activation of a limited set of homeobox genes and Hox coregulators that are consistently expressed in MLL-associated leukemias [42].
  • Multiple copies of the GLUT2TAAT motif were ligated 5' to a heterologous promoter and transfected into a PDX-1-expressing cell line (beta TC3) and into cell lines lacking the homeobox factor (InR1-G9 and JEG-3) [43].
  • The present study examined the effects of SNH on homeobox genes in the colon cancer cell line HT 29 that expresses VIP receptors [44].

Other interactions of LBX1

  • This duplicated region contained a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and beta-TRCP genes, known to be involved in limb development [45].
  • Thus, LBX1 and the protooncogene HOX11 map to a common chromosomal region, as do their Drosophila counterparts, the lady bird and 93Bal genes [1].
  • Here, we report the cloning and sequencing of 31 homeobox (HB) sequences, identified using degenerate oligodeoxyribonucleotide primers, in a polymerase chain reaction with cDNA derived from a purified CD34+ population of human haemopoietic cells [22].
  • Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects [46].
  • A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD [47].

Analytical, diagnostic and therapeutic context of LBX1

  • Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR [48].
  • Immunohistochemistry on appendicular sections after E10.5 demonstrated that Pitx2 neatly marked the areas of muscle anlagen, that Pax3, Lbx1, and the muscle regulatory factors (MRFs) stained only subsets of Pitx2(+) cells within these areas, and that virtually all Pitx2(+) cells in these areas express at least one of these known myogenic markers [49].
  • Gene targeting in mouse embryo-derived stem cells has been used to disrupt the homeobox gene hox-1 [50].
  • Zmhox1a (Zea mays homeobox) is an unidentified maize gene mapping to the long arm of chromosome 8 [51].
  • Sequence analysis and expression patterns divide the maize knotted1-like homeobox genes into two classes [52].


  1. Mouse Lbx1 and human LBX1 define a novel mammalian homeobox gene family related to the Drosophila lady bird genes. Jagla, K., Dollé, P., Mattei, M.G., Jagla, T., Schuhbaur, B., Dretzen, G., Bellard, F., Bellard, M. Mech. Dev. (1995) [Pubmed]
  2. HOXD3-overexpression increases integrin alphavbeta3 expression and deprives E-cadherin while it enhances cell motility in A549 cells. Ohta, H., Hamada, J., Tada, M., Aoyama, T., Furuuchi, K., Takahashi, Y., Totsuka, Y., Moriuchi, T. Clin. Exp. Metastasis (2006) [Pubmed]
  3. Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Glaser, T., Walton, D.S., Maas, R.L. Nat. Genet. (1992) [Pubmed]
  4. Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. Hiroi, Y., Kudoh, S., Monzen, K., Ikeda, Y., Yazaki, Y., Nagai, R., Komuro, I. Nat. Genet. (2001) [Pubmed]
  5. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Dattani, M.T., Martinez-Barbera, J.P., Thomas, P.Q., Brickman, J.M., Gupta, R., Mårtensson, I.L., Toresson, H., Fox, M., Wales, J.K., Hindmarsh, P.C., Krauss, S., Beddington, R.S., Robinson, I.C. Nat. Genet. (1998) [Pubmed]
  6. Decreased thalamic expression of the homeobox gene DLX1 in psychosis. Kromkamp, M., Uylings, H.B., Smidt, M.P., Hellemons, A.J., Burbach, J.P., Kahn, R.S. Arch. Gen. Psychiatry (2003) [Pubmed]
  7. The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development. Gottlieb, S., Emanuel, B.S., Driscoll, D.A., Sellinger, B., Wang, Z., Roe, B., Budarf, M.L. Am. J. Hum. Genet. (1997) [Pubmed]
  8. Transcriptional control of the cell cycle in mammary gland development and tumorigenesis. Coletta, R.D., Jedlicka, P., Gutierrez-Hartmann, A., Ford, H.L. Journal of mammary gland biology and neoplasia. (2004) [Pubmed]
  9. Similarities in genetic mental retardation and neuroteratogenic syndromes. Adams, J. Pharmacol. Biochem. Behav. (1996) [Pubmed]
  10. The roles of retinoids in vertebrate development. Means, A.L., Gudas, L.J. Annu. Rev. Biochem. (1995) [Pubmed]
  11. Homeobox galore: when reproduction goes RHOX and roll. Hogeveen, K.N., Sassone-Corsi, P. Cell (2005) [Pubmed]
  12. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/- compound mutant mice. Aoki, K., Tamai, Y., Horiike, S., Oshima, M., Taketo, M.M. Nat. Genet. (2003) [Pubmed]
  13. Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Amiel, J., Laudier, B., Attié-Bitach, T., Trang, H., de Pontual, L., Gener, B., Trochet, D., Etchevers, H., Ray, P., Simonneau, M., Vekemans, M., Munnich, A., Gaultier, C., Lyonnet, S. Nat. Genet. (2003) [Pubmed]
  14. Sequential activation of HOX2 homeobox genes by retinoic acid in human embryonal carcinoma cells. Simeone, A., Acampora, D., Arcioni, L., Andrews, P.W., Boncinelli, E., Mavilio, F. Nature (1990) [Pubmed]
  15. Alteration of homeobox gene expression by N-ras transformation of PA-1 human teratocarcinoma cells. Buettner, R., Yim, S.O., Hong, Y.S., Boncinelli, E., Tainsky, M.A. Mol. Cell. Biol. (1991) [Pubmed]
  16. Gene expression profiling of human sarcomas: insights into sarcoma biology. Baird, K., Davis, S., Antonescu, C.R., Harper, U.L., Walker, R.L., Chen, Y., Glatfelter, A.A., Duray, P.H., Meltzer, P.S. Cancer Res. (2005) [Pubmed]
  17. A role for the homeobox protein Distal-less 3 in the activation of the glycoprotein hormone alpha subunit gene in choriocarcinoma cells. Roberson, M.S., Meermann, S., Morasso, M.I., Mulvaney-Musa, J.M., Zhang, T. J. Biol. Chem. (2001) [Pubmed]
  18. A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer. He, W.W., Sciavolino, P.J., Wing, J., Augustus, M., Hudson, P., Meissner, P.S., Curtis, R.T., Shell, B.K., Bostwick, D.G., Tindall, D.J., Gelmann, E.P., Abate-Shen, C., Carter, K.C. Genomics (1997) [Pubmed]
  19. Pax6 Regulation in Retinal Cells by CCCTC Binding Factor. Li, T., Lu, Z., Lu, L. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  20. Transforming potential of the T-cell acute lymphoblastic leukemia-associated homeobox genes HOXA13, TLX1, and TLX3. Su, X., Drabkin, H., Clappier, E., Morgado, E., Busson, M., Romana, S., Soulier, J., Berger, R., Bernard, O.A., Lavau, C. Genes Chromosomes Cancer (2006) [Pubmed]
  21. Deletions of 2q14 that include the homeobox engrailed 1 (EN1) transcription factor are compatible with a normal phenotype. Barber, J.C., Maloney, V.K., Bewes, B., Wakeling, E. Eur. J. Hum. Genet. (2006) [Pubmed]
  22. Identification of homeobox genes expressed in human haemopoietic progenitor cells. Moretti, P., Simmons, P., Thomas, P., Haylock, D., Rathjen, P., Vadas, M., D'Andrea, R. Gene (1994) [Pubmed]
  23. Human Hox-4.2 and Drosophila deformed encode similar regulatory specificities in Drosophila embryos and larvae. McGinnis, N., Kuziora, M.A., McGinnis, W. Cell (1990) [Pubmed]
  24. Nuclear Factor Y Drives Basal Transcription of the Human TLX3, a Gene Overexpressed in T-Cell Acute Lymphocytic Leukemia. Borghini, S., Vargiolu, M., Di Duca, M., Ravazzolo, R., Ceccherini, I. Mol. Cancer Res. (2006) [Pubmed]
  25. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. Self, M., Lagutin, O.V., Bowling, B., Hendrix, J., Cai, Y., Dressler, G.R., Oliver, G. EMBO J. (2006) [Pubmed]
  26. Effect of CTCF-binding motif on regulation of PAX6 transcription. Wu, D., Li, T., Lu, Z., Dai, W., Xu, M., Lu, L. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  27. Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor. Freund, C.L., Gregory-Evans, C.Y., Furukawa, T., Papaioannou, M., Looser, J., Ploder, L., Bellingham, J., Ng, D., Herbrick, J.A., Duncan, A., Scherer, S.W., Tsui, L.C., Loutradis-Anagnostou, A., Jacobson, S.G., Cepko, C.L., Bhattacharya, S.S., McInnes, R.R. Cell (1997) [Pubmed]
  28. Retinopathy and attenuated circadian entrainment in Crx-deficient mice. Furukawa, T., Morrow, E.M., Li, T., Davis, F.C., Cepko, C.L. Nat. Genet. (1999) [Pubmed]
  29. Involvement of Per-Arnt-Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose. da Silva Xavier, G., Rutter, J., Rutter, G.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  30. Lymphoid expression and TATAA binding of a human protein containing an Antennapedia homeodomain. Baier, L.J., Hannibal, M.C., Hanley, E.W., Nabel, G.J. Blood (1991) [Pubmed]
  31. Mutation in the RIEG1 gene in patients with iridogoniodysgenesis syndrome. Kulak, S.C., Kozlowski, K., Semina, E.V., Pearce, W.G., Walter, M.A. Hum. Mol. Genet. (1998) [Pubmed]
  32. Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers. Voeller, H.J., Augustus, M., Madike, V., Bova, G.S., Carter, K.C., Gelmann, E.P. Cancer Res. (1997) [Pubmed]
  33. Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10. Bae, N.S., Swanson, M.J., Vassilev, A., Howard, B.H. J. Biochem. (2004) [Pubmed]
  34. Down-regulation of homeobox gene GBX2 expression inhibits human prostate cancer clonogenic ability and tumorigenicity. Gao, A.C., Lou, W., Isaacs, J.T. Cancer Res. (1998) [Pubmed]
  35. Pathogenesis of pre-neoplastic lesions of the stomach: targets for prevention. Leung, W.K., Sung, J.J. Digestive diseases (Basel, Switzerland) (2004) [Pubmed]
  36. The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes. Dear, T.N., Sanchez-Garcia, I., Rabbitts, T.H. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  37. Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis. Park, K., Kim, K., Rho, S.B., Choi, K., Kim, D., Oh, S.H., Park, J., Lee, S.H., Lee, J.H. Cancer Res. (2005) [Pubmed]
  38. HOXC13 is involved in the regulation of human hair keratin gene expression. Jave-Suarez, L.F., Winter, H., Langbein, L., Rogers, M.A., Schweizer, J. J. Biol. Chem. (2002) [Pubmed]
  39. Transcriptional repression of the cystic fibrosis transmembrane conductance regulator gene, mediated by CCAAT displacement protein/cut homolog, is associated with histone deacetylation. Li, S., Moy, L., Pittman, N., Shue, G., Aufiero, B., Neufeld, E.J., LeLeiko, N.S., Walsh, M.J. J. Biol. Chem. (1999) [Pubmed]
  40. A complex containing PBX2 contributes to activation of the proto-oncogene HOX11. Brake, R.L., Kees, U.R., Watt, P.M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  41. Fusion of ETV6 to the caudal-related homeobox gene CDX2 in acute myeloid leukemia with the t(12;13)(p13;q12). Chase, A., Reiter, A., Burci, L., Cazzaniga, G., Biondi, A., Pickard, J., Roberts, I.A., Goldman, J.M., Cross, N.C. Blood (1999) [Pubmed]
  42. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Zeisig, B.B., Milne, T., García-Cuéllar, M.P., Schreiner, S., Martin, M.E., Fuchs, U., Borkhardt, A., Chanda, S.K., Walker, J., Soden, R., Hess, J.L., Slany, R.K. Mol. Cell. Biol. (2004) [Pubmed]
  43. Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Waeber, G., Thompson, N., Nicod, P., Bonny, C. Mol. Endocrinol. (1996) [Pubmed]
  44. A vasoactive intestinal peptide receptor analog alters the expression of homeobox genes. Steingart, R.A., Heldenberg, E., Pinhasov, A., Brenneman, D.E., Fridkin, M., Gozes, I. Life Sci. (2002) [Pubmed]
  45. A genomic rearrangement resulting in a tandem duplication is associated with split hand-split foot malformation 3 (SHFM3) at 10q24. de Mollerat, X.J., Gurrieri, F., Morgan, C.T., Sangiorgi, E., Everman, D.B., Gaspari, P., Amiel, J., Bamshad, M.J., Lyle, R., Blouin, J.L., Allanson, J.E., Le Marec, B., Wilson, M., Braverman, N.E., Radhakrishna, U., Delozier-Blanchet, C., Abbott, A., Elghouzzi, V., Antonarakis, S., Stevenson, R.E., Munnich, A., Neri, G., Schwartz, C.E. Hum. Mol. Genet. (2003) [Pubmed]
  46. Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects. Mavrogiannis, L.A., Antonopoulou, I., Baxová, A., Kutílek, S., Kim, C.A., Sugayama, S.M., Salamanca, A., Wall, S.A., Morriss-Kay, G.M., Wilkie, A.O. Nat. Genet. (2001) [Pubmed]
  47. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Semina, E.V., Ferrell, R.E., Mintz-Hittner, H.A., Bitoun, P., Alward, W.L., Reiter, R.S., Funkhauser, C., Daack-Hirsch, S., Murray, J.C. Nat. Genet. (1998) [Pubmed]
  48. High Expression of the ETS Transcription Factor ERG Predicts Adverse Outcome in Acute T-Lymphoblastic Leukemia in Adults. Baldus, C.D., Burmeister, T., Martus, P., Schwartz, S., G??kbuget, N., Bloomfield, C.D., Hoelzer, D., Thiel, E., Hofmann, W.K. J. Clin. Oncol. (2006) [Pubmed]
  49. Expression pattern of the homeodomain transcription factor Pitx2 during muscle development. Shih, H.P., Gross, M.K., Kioussi, C. Gene Expr. Patterns (2007) [Pubmed]
  50. Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Chisaka, O., Capecchi, M.R. Nature (1991) [Pubmed]
  51. Zmhox1a, the product of a novel maize homeobox gene, interacts with the Shrunken 26 bp feedback control element. Bellmann, R., Werr, W. EMBO J. (1992) [Pubmed]
  52. Sequence analysis and expression patterns divide the maize knotted1-like homeobox genes into two classes. Kerstetter, R., Vollbrecht, E., Lowe, B., Veit, B., Yamaguchi, J., Hake, S. Plant Cell (1994) [Pubmed]
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