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Gene Review

HOXB5  -  homeobox B5

Homo sapiens

Synonyms: HHO.C10, HOX2, HOX2A, HU-1, Homeobox protein HHO.C10, ...
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Disease relevance of HOXB5

  • We hypothesized that Hoxb-5 is similarly involved in human lung branching morphogenesis, and is abnormally expressed in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), both of which are congenital lung malformations with abnormal airway development [1].
  • Six contiguous genes of the HOX2 locus, highly expressed in acute non-lymphocytic leukemia, are switched off in chronic myelogenous leukemia, suggesting that down-regulation of HOX2 genes might be required for cell maturation of the myeloid lineages [2].
  • The glioblastoma cell line, 251-MG expresses almost all of the genes of the HOX2 locus [3].
  • The two uninduced neuroblastoma cell lines show a similar pattern of expression for a number of HOX2 genes although the levels of expression are different for individual cell lines [3].
  • The embryonal carcinoma cell line F9 expresses low levels of several HOX2 genes which is restricted to the 5' region of the HOX2 cluster [3].

High impact information on HOXB5

  • Quite unexpectedly, hoxb-5, hoxb-6 transheterozygotes (hoxb-5-hoxb-6+/hoxb-5+ hoxb-6-) also show the third phenotype [4].
  • The third phenotype, an anteriorizing homeotic transformation of the cervicothoracic vertebrae from C6 through T1, is common to both hoxb-5- and hoxb-6- homozygotes [4].
  • The human HoxB5 (Hox-2.1) gene product is a sequence-specific DNA binding protein [5].
  • Recently, it has been shown that expression of human HOX 2 genes is sequentially activated by RA beginning from Hox 2.9 at the 3' end of the HOX 2 cluster (A. Simeone, D. Acampora, L. Arcioni, P. W. Andrews, E. Boncinelli, and F. Mavilio, Nature [London] 346:763-766, 1990) [6].
  • HOX2 includes 9 homeoboxes in 180 kb on chromosome 17 [7].

Biological context of HOXB5

  • Neuron and glia differentiation of NCCs are concomitant with HOXB5 down-regulation in NCCs and the mesenchyme [8].
  • CONCLUSIONS: Hoxb-5 expression during human lung branching morphogenesis, which is similar to that observed in mouse lung development, indicates that it plays a role in controlling airway patterning [1].
  • The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5 [9].
  • They have the same 5'-3' transcriptional orientation and are clustered with three previously described HOX-2 homeoboxes (5'-2.5-2.4-2.3-2.2-2.1-2.6-2.7-2.8-3') [10].
  • We have investigated the structure of the human HOX-2 locus, which encompasses a 90-kb region on chromosome 17q21 [10].

Anatomical context of HOXB5

  • HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts [8].
  • Immunocytochemistry showed Hoxb-5 protein expression in mesenchymal cells around branching airways in the pseuodglandular period, subepithelial fibroblast localization (especially at airway branch points) in the CAN and minimal expression in the ALV [1].
  • Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system [10].
  • The only exception was the lung carcinoma cell line HU-1 [11].
  • Human HU-1 carcinoma cells in culture synthesize several homologous laminin chains and regulate the process of assembly, secretion and deposition of laminin variants into tumor basement membranes [11].

Associations of HOXB5 with chemical compounds

  • Expression of hoxa-4, hoxd-3, and hoxb-5 was increased in cardiogenic tissue treated with RA in culture conditions that also produced changes in positionally restricted cardiomyogenic phenotypes [12].
  • Streptozotocin treatment increased expression of Hoxb-5 at 18 d of gestation, but did not affect Hoxa-5 expression [13].

Other interactions of HOXB5

  • Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation [4].
  • Thyroid transcription factor 1 and Hoxb5 are down-regulated by TO, suggesting that duration and timing of occlusion are important in balancing the effects of TO on lung growth vs lung maturation [14].
  • The authors previously have shown that the homeobox gene Hoxb-5 is necessary for normal airway branching during lung development [15].

Analytical, diagnostic and therapeutic context of HOXB5

  • Viral antigen-positive cells detected by immunofluorescence using an antibody specific for the IE-1 antigen of HCMV appeared as clusters among the population of cells in which the HOX2A transcript was detected [16].
  • Western blots showed high Hoxb-5 protein levels in the pseudoglandular period (PSG), decreased but sustained levels in the canalicular period (CAN), and negligible levels during the alveolar period (ALV) [1].
  • We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis [10].


  1. Expression of Hoxb-5 during human lung development and in congenital lung malformations. Volpe, M.V., Pham, L., Lessin, M., Ralston, S.J., Bhan, I., Cutz, E., Nielsen, H.C. Birth defects research. Part A, Clinical and molecular teratology. (2003) [Pubmed]
  2. Characteristic patterns of HOX gene expression in different types of human leukemia. Celetti, A., Barba, P., Cillo, C., Rotoli, B., Boncinelli, E., Magli, M.C. Int. J. Cancer (1993) [Pubmed]
  3. Modulation of HOX2 gene expression following differentiation of neuronal cell lines. Safaei, R., Prochazka, V., Detmer, K., Boncinelli, E., Lawrence, H.J., Largman, C. Differentiation (1992) [Pubmed]
  4. Genetic interaction between hoxb-5 and hoxb-6 is revealed by nonallelic noncomplementation. Rancourt, D.E., Tsuzuki, T., Capecchi, M.R. Genes Dev. (1995) [Pubmed]
  5. Cooperative DNA binding of the human HoxB5 (Hox-2.1) protein is under redox regulation in vitro. Galang, C.K., Hauser, C.A. Mol. Cell. Biol. (1993) [Pubmed]
  6. 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]
  7. The human HOX gene family. Acampora, D., D'Esposito, M., Faiella, A., Pannese, M., Migliaccio, E., Morelli, F., Stornaiuolo, A., Nigro, V., Simeone, A., Boncinelli, E. Nucleic Acids Res. (1989) [Pubmed]
  8. HOXB5 expression is spatially and temporarily regulated in human embryonic gut during neural crest cell colonization and differentiation of enteric neuroblasts. Fu, M., Chi Hang Lui, V., Har Sham, M., Nga Yin Cheung, A., Kwong Hang Tam, P. Dev. Dyn. (2003) [Pubmed]
  9. Unusual gene order and organization of the sea urchin hox cluster. Cameron, R.A., Rowen, L., Nesbitt, R., Bloom, S., Rast, J.P., Berney, K., Arenas-Mena, C., Martinez, P., Lucas, S., Richardson, P.M., Davidson, E.H., Peterson, K.J., Hood, L. J. exp. zool. B. Mol. Dev. Evol. (2006) [Pubmed]
  10. Differential expression of human HOX-2 genes along the anterior-posterior axis in embryonic central nervous system. Giampaolo, A., Acampora, D., Zappavigna, V., Pannese, M., D'Esposito, M., Carè, A., Faiella, A., Stornaiuolo, A., Russo, G., Simeone, A. Differentiation (1989) [Pubmed]
  11. Selective assembly of laminin variants by human carcinoma cells. Wewer, U.M., Wayner, E.A., Hoffstrom, B.G., Lan, F., Meyer-Nielsen, B., Engvall, E., Albrechtsen, R. Lab. Invest. (1994) [Pubmed]
  12. Analysis of Hox gene expression during early avian heart development. Searcy, R.D., Yutzey, K.E. Dev. Dyn. (1998) [Pubmed]
  13. Fetal lung mRNA levels of Hox genes are differentially altered by maternal diabetes and butyrate in rats. Jacobs, H.C., Bogue, C.W., Pinter, E., Wilson, C.M., Warshaw, J.B., Gross, I. Pediatr. Res. (1998) [Pubmed]
  14. Tracheal occlusion in fetal rats alters expression of mesenchymal nuclear transcription factors without affecting surfactant protein expression. Danzer, E., Robinson, L.E., Davey, M.G., Schwarz, U., Volpe, M., Adzick, N.S., Flake, A.W., Hedrick, H.L. J. Pediatr. Surg. (2006) [Pubmed]
  15. Association of bronchopulmonary sequestration with expression of the homeobox protein Hoxb-5. Volpe, M.V., Archavachotikul, K., Bhan, I., Lessin, M.S., Nielsen, H.C. J. Pediatr. Surg. (2000) [Pubmed]
  16. Relationship between HOX2 homeobox gene expression and the human cytomegalovirus immediate early genes. Kadota, C., Nagahama, M., Tsutsui, Y. J. Gen. Virol. (1992) [Pubmed]
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