antennapedia homeodomain protein


Summary: Antennapedia homeodomain protein is a homeobox protein involved in limb patterning in ARTHROPODS. Mutations in the gene for the antennapedia homeodomain protein are associated with the conversion of antenna to leg or leg to antenna DROSOPHILA.

Top Publications

  1. Drin G, Cottin S, Blanc E, Rees A, Temsamani J. Studies on the internalization mechanism of cationic cell-penetrating peptides. J Biol Chem. 2003;278:31192-201 pubmed
    ..Altogether, our results suggest that SynB and pAntp-(43-58) peptides penetrate into cells by an adsorptive-mediated endocytosis process rather than temperature-independent translocation. ..
  2. Plescia J, Salz W, Xia F, Pennati M, Zaffaroni N, Daidone M, et al. Rational design of shepherdin, a novel anticancer agent. Cancer Cell. 2005;7:457-68 pubmed
    ..Systemic administration of shepherdin in vivo is well tolerated, and inhibits human tumor growth in mice without toxicity. Shepherdin could provide a potent and selective anticancer agent in humans. ..
  3. Joliot A, Pernelle C, Deagostini Bazin H, Prochiantz A. Antennapedia homeobox peptide regulates neural morphogenesis. Proc Natl Acad Sci U S A. 1991;88:1864-8 pubmed
  4. Prochiantz A. Getting hydrophilic compounds into cells: lessons from homeopeptides. Curr Opin Neurobiol. 1996;6:629-34 pubmed
    ..e. other peptides and oligonucleotides) into the cytoplasm and nucleus of all cell types. This article describes our present understanding of this phenomenon and discusses its potential applications in cell biology. ..
  5. Derossi D, Calvet S, Trembleau A, Brunissen A, Chassaing G, Prochiantz A. Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent. J Biol Chem. 1996;271:18188-93 pubmed
    ..1995) J. Neurosci. 15, 7158-7167). Therefore, in addition to their physiological implications (Prochiantz, A., and Théodore, L.(1995) BioEssays 17, 39-45), the present results open the way to the molecular design of cellular vectors. ..
  6. Terrone D, Sang S, Roudaia L, Silvius J. Penetratin and related cell-penetrating cationic peptides can translocate across lipid bilayers in the presence of a transbilayer potential. Biochemistry. 2003;42:13787-99 pubmed
  7. Persson D, Thorén P, Lincoln P, Norden B. Vesicle membrane interactions of penetratin analogues. Biochemistry. 2004;43:11045-55 pubmed
    ..Finally, significant changes of the contributions to CD spectra from aromatic residues due to their insertion into the membrane were observed. ..
  8. Rogers F, Manoharan M, Rabinovitch P, Ward D, Glazer P. Peptide conjugates for chromosomal gene targeting by triplex-forming oligonucleotides. Nucleic Acids Res. 2004;32:6595-604 pubmed
    ..These results suggest that peptide conjugation may enhance intranuclear delivery of reagents designed to bind to chromosomal DNA. ..
  9. Monteiro A, Schierwater B, Dellaporta S, Holland P. A low diversity of ANTP class homeobox genes in Placozoa. Evol Dev. 2006;8:174-82 pubmed
    ..The low diversity of ANTP class genes isolated in Trichoplax can be reconciled with the low anatomical complexity of this animal, although the finding that these genes are assignable to recognized gene families is intriguing. ..

More Information


  1. Richelle Maurer E, Boury Esnault N, Itskovich V, Manuel M, Pomponi S, Van de Vyver G, et al. Conservation and phylogeny of a novel family of non-Hox genes of the Antp class in Demospongiae (porifera). J Mol Evol. 2006;63:222-30 pubmed
    ..As for their expression, high levels of Demox transcripts were found in adult tissues. Our data add to the number of published poriferan homeobox sequences and provide independent confirmation of the current Demospongiae phylogenies. ..
  2. Kamm K, Schierwater B. Ancient complexity of the non-Hox ANTP gene complement in the anthozoan Nematostella vectensis: implications for the evolution of the ANTP superclass. J Exp Zool B Mol Dev Evol. 2006;306:589-96 pubmed
    ..We conclude that the last cnidarian/bilaterian ancestor already harboured the almost full complement of non-Hox ANTP genes before the Hox system evolved. ..
  3. Holland P, Booth H, Bruford E. Classification and nomenclature of all human homeobox genes. BMC Biol. 2007;5:47 pubmed
    ..The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass. ..
  4. Papadopoulos D, Resendez Perez D, Cárdenas Chávez D, Villanueva Segura K, Canales del Castillo R, Felix D, et al. Functional synthetic Antennapedia genes and the dual roles of YPWM motif and linker size in transcriptional activation and repression. Proc Natl Acad Sci U S A. 2011;108:11959-64 pubmed publisher
  5. Gorfinkiel N, Fanti L, Melgar T, García E, Pimpinelli S, Guerrero I, et al. The Drosophila Polycomb group gene Sex combs extra encodes the ortholog of mammalian Ring1 proteins. Mech Dev. 2004;121:449-62 pubmed
    ..We also show that Ring/Sce interacts directly with PcG proteins, as it occurs in mammals. ..
  6. Larroux C, Fahey B, Degnan S, Adamski M, Rokhsar D, Degnan B. The NK homeobox gene cluster predates the origin of Hox genes. Curr Biol. 2007;17:706-10 pubmed
    ..The maintenance of the NK cluster in sponges and bilaterians for greater than 550 million years is likely to reflect regulatory constraints inherent to the organization of this ancient cluster...
  7. Kabouridis P. Biological applications of protein transduction technology. Trends Biotechnol. 2003;21:498-503 pubmed
    ..It also considers future directions and the potential of this technology to move from the laboratory into the clinic. ..
  8. Bellet Amalric E, Blaudez D, Desbat B, Graner F, Gauthier F, Renault A. Interaction of the third helix of Antennapedia homeodomain and a phospholipid monolayer, studied by ellipsometry and PM-IRRAS at the air-water interface. Biochim Biophys Acta. 2000;1467:131-43 pubmed
    ..Determination of the structure and orientation of peptides and lipids (separately or together) evidenced that electrostatic rather than amphiphilic interactions determine the peptide adsorption and its action on lipids. ..
  9. Derossi D, Joliot A, Chassaing G, Prochiantz A. The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem. 1994;269:10444-50 pubmed
    ..Finally, substitution of two tryptophans by two phenylalanines strongly diminishes translocation, raising the possibility that the internalization of the third helix is not solely based on its general hydrophobicity. ..
  10. Li X, McGinnis W. Activity regulation of Hox proteins, a mechanism for altering functional specificity in development and evolution. Proc Natl Acad Sci U S A. 1999;96:6802-7 pubmed
    ..The acquisition of novel activation and repression potentials in Hox proteins may be an important mechanism underlying the generation of subtle morphological differences during evolution. ..
  11. Cribbs D, Benassayag C, Randazzo F, Kaufman T. Levels of homeotic protein function can determine developmental identity: evidence from low-level expression of the Drosophila homeotic gene proboscipedia under Hsp70 control. EMBO J. 1995;14:767-78 pubmed
    ..These observations support a crucial role for quantitative aspects of pb function in determining segmental identity, including cross-regulatory events involved in this determination. ..
  12. Carroll S, Weatherbee S, Langeland J. Homeotic genes and the regulation and evolution of insect wing number. Nature. 1995;375:58-61 pubmed
  13. Avignolo C, Bagnasco L, Biasotti B, Melchiori A, Tomati V, Bauer I, et al. Internalization via Antennapedia protein transduction domain of an scFv antibody toward c-Myc protein. FASEB J. 2008;22:1237-45 pubmed
    ..Miniantibodies capable of penetrating cell membranes dramatically broaden the potential for innovative therapeutic agents and attack of new targets. ..
  14. Roy S, Jiang N, Hart C. Lack of the Drosophila BEAF insulator proteins alters regulation of genes in the Antennapedia complex. Mol Genet Genomics. 2011;285:113-23 pubmed publisher
    ..A control gene, Dref, was not affected. A full understanding of the regulation of ANT-C genes during development will have to take the role of BEAF into account. ..
  15. Zhang H, Shinmyo Y, Mito T, Miyawaki K, Sarashina I, Ohuchi H, et al. Expression patterns of the homeotic genes Scr, Antp, Ubx, and abd-A during embryogenesis of the cricket Gryllus bimaculatus. Gene Expr Patterns. 2005;5:491-502 pubmed
    ..abd-A is expressed in the posterior compartment of the first abdominal segment and the remaining abdominal segments in all three insects, although its posterior border varies among them. ..
  16. Casares F, Mann R. The ground state of the ventral appendage in Drosophila. Science. 2001;293:1477-80 pubmed
    ..These results raise the possibility that, during evolution, leglike appendages could have developed without selector gene activity. ..
  17. Hayward D, Patel N, Rehm E, Goodman C, Ball E. Sequence and expression of grasshopper antennapedia: comparison to Drosophila. Dev Biol. 1995;172:452-65 pubmed publisher
    ..In the CNS expression is initially limited to a few neurons, but eventually becomes widespread. Both insects show strong expression in certain homologous identified neurons and similar temporal modulation of expression...
  18. Bello B, Holbro N, Reichert H. Polycomb group genes are required for neural stem cell survival in postembryonic neurogenesis of Drosophila. Development. 2007;134:1091-9 pubmed
    ..Moreover, together with data on mammalian PcG genes, they imply that repression of aberrant reactivation of Hox genes may be a general and evolutionarily conserved role for PcG genes in CNS development. ..
  19. Kotelevets L, van Hengel J, Bruyneel E, Mareel M, van Roy F, Chastre E. Implication of the MAGI-1b/PTEN signalosome in stabilization of adherens junctions and suppression of invasiveness. FASEB J. 2005;19:115-7 pubmed
  20. Bantignies F, Roure V, Comet I, Leblanc B, Schuettengruber B, Bonnet J, et al. Polycomb-dependent regulatory contacts between distant Hox loci in Drosophila. Cell. 2011;144:214-26 pubmed publisher
    ..Thus, the three-dimensional organization of Polycomb target genes in the cell nucleus stabilizes the maintenance of epigenetic gene silencing. ..
  21. Perrin L, Monier B, Ponzielli R, Astier M, Semeriva M. Drosophila cardiac tube organogenesis requires multiple phases of Hox activity. Dev Biol. 2004;272:419-31 pubmed
    ..This analysis illustrates the mechanisms by which Hox genes can orchestrate organogenesis and, in particular, allows a clear uncoupling of the different phases of Hox activity in this process. ..
  22. Gutierrez L, Oktaba K, Scheuermann J, Gambetta M, Ly Hartig N, Muller J. The role of the histone H2A ubiquitinase Sce in Polycomb repression. Development. 2012;139:117-27 pubmed publisher
    ..Sce synergizes with the Polycomb repressive deubiquitinase (PR-DUB) complex to repress transcription at class I genes, suggesting that H2A monoubiquitylation must be appropriately balanced for their transcriptional repression. ..
  23. Zhu L, Schwegler Berry D, Castranova V, He P. Internalization of caveolin-1 scaffolding domain facilitated by Antennapedia homeodomain attenuates PAF-induced increase in microvessel permeability. Am J Physiol Heart Circ Physiol. 2004;286:H195-201 pubmed
  24. Takano M, Meneshian A, Sheikh E, Yamakawa Y, Wilkins K, Hopkins E, et al. Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation. Am J Physiol Heart Circ Physiol. 2002;283:H2054-61 pubmed
  25. Miller D, Holtzman S, Kalkbrenner A, Kaufman T. Homeotic Complex (Hox) gene regulation and homeosis in the mesoderm of the Drosophila melanogaster embryo: the roles of signal transduction and cell autonomous regulation. Mech Dev. 2001;102:17-32 pubmed
    ..We find that extrinsic specification of cell fate by signaling can be overridden by Hox protein expression in mesodermal cells and propose the term autonomic dominance for this phenomenon. ..
  26. Kremser T, Hasenpusch Theil K, Wagner E, Buttgereit D, Renkawitz Pohl R. Expression of the beta3 tubulin gene (beta Tub60D) in the visceral mesoderm of Drosophila is dependent on a complex enhancer that binds Tinman and UBX. Mol Gen Genet. 1999;262:643-58 pubmed
    ..Thus the vm1 enhancer of the beta3 tubulin gene contains a complex array of elements that are involved in transactivation by a combination of tissue- and position-specific factors including Tinman and UBX. ..
  27. Dong P, Chu J, Panganiban G. Coexpression of the homeobox genes Distal-less and homothorax determines Drosophila antennal identity. Development. 2000;127:209-16 pubmed
    ..Based on their genetic and biochemical properties, we propose that Homothorax and Extradenticle may serve as antenna-specific cofactors for Distal-less. ..
  28. Hui J, McDougall C, Monteiro A, Holland P, Arendt D, Balavoine G, et al. Extensive chordate and annelid macrosynteny reveals ancestral homeobox gene organization. Mol Biol Evol. 2012;29:157-65 pubmed publisher
    ..dumerilii and chordates. This implies a very low rate of interchromosomal genome rearrangement in the lineages leading to P. dumerilii and the chordate ancestor since the time of the PDA. ..
  29. Brodu V, Elstob P, Gould A. abdominal A specifies one cell type in Drosophila by regulating one principal target gene. Development. 2002;129:2957-63 pubmed
    ..This raises the possibility that much of the overall Hox downstream complexity results from cascades of indirect regulation and cell-to-cell heterogeneity. ..
  30. Furukubo Tokunaga K, Flister S, Gehring W. Functional specificity of the Antennapedia homeodomain. Proc Natl Acad Sci U S A. 1993;90:6360-4 pubmed
  31. Garcia Echeverria C, Furet P, Chene P. Coupling of the antennapedia third helix to a potent antagonist of the p53/hdm2 protein-protein interaction. Bioorg Med Chem Lett. 2001;11:2161-4 pubmed
    ..To accomplish this, a protocol has been implemented to couple the antennapedia third helix (residues 43-58) to a potent antagonist of the p53/hdm2 protein-protein interaction without affecting its in vitro inhibitory activity. ..
  32. Khadjeh S, Turetzek N, Pechmann M, Schwager E, Wimmer E, Damen W, et al. Divergent role of the Hox gene Antennapedia in spiders is responsible for the convergent evolution of abdominal limb repression. Proc Natl Acad Sci U S A. 2012;109:4921-6 pubmed publisher
    ..Our results illustrate an interesting example of convergent evolution of abdominal leg repression in arthropods by altering the role of distinct Hox genes at different levels of their action...
  33. Takeshita K, Bollekens J, Hijiya N, Ratajczak M, Ruddle F, Gewirtz A. A homeobox gene of the Antennapedia class is required for human adult erythropoiesis. Proc Natl Acad Sci U S A. 1993;90:3535-8 pubmed
    ..These results show that Hox-3.3 is involved in an early step in the proliferation of the erythroid colony-forming unit subset of progenitor cells. ..
  34. Hudecz F, Bánóczi Z, Csík G. Medium-sized peptides as built in carriers for biologically active compounds. Med Res Rev. 2005;25:679-736 pubmed
    ..A brief note will refer to the present understanding on the uptake mechanism at the end of each section. ..
  35. Wu X, Gehring W. Cellular uptake of the Antennapedia homeodomain polypeptide by macropinocytosis. Biochem Biophys Res Commun. 2014;443:1136-40 pubmed publisher
    ..Our results identify macropinocytosis as a major mechanism by which Antennapedia homeodomain obtains the access to the interior of cells, providing a novel perspective in the field of protein translocation and transduction. ..
  36. Michaut L, Jansen H, Bardine N, Durston A, Gehring W. Analyzing the function of a hox gene: an evolutionary approach. Dev Growth Differ. 2011;53:982-93 pubmed publisher
    ..The results indicate that relatively few of the early Hox target genes are conserved: these are mainly involved in the specification of the antero-posterior body axis and in gastrulation. ..
  37. Hueber S, Rauch J, Djordjevic M, Gunter H, Weiller G, Frickey T. Analysis of central Hox protein types across bilaterian clades: on the diversification of central Hox proteins from an Antennapedia/Hox7-like protein. Dev Biol. 2013;383:175-85 pubmed publisher
  38. Gould A, Morrison A, Sproat G, White R, Krumlauf R. Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns. Genes Dev. 1997;11:900-13 pubmed
    ..Therefore, despite many well documented aspects of Hox structural and functional conservation, there are mechanistic differences in Hox complex regulation between arthropods and vertebrates. ..
  39. Miller C, McGehee R, Habener J. IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene. EMBO J. 1994;13:1145-56 pubmed
  40. Ekker S, Jackson D, von Kessler D, Sun B, Young K, Beachy P. The degree of variation in DNA sequence recognition among four Drosophila homeotic proteins. EMBO J. 1994;13:3551-60 pubmed
    ..This and other patterns of residue conservation suggest that differential DNA sequence recognition may play a role in HOM protein function in a wide range of organisms. ..
  41. Percival Smith A, Teft W, Barta J. Tarsus determination in Drosophila melanogaster. Genome. 2005;48:712-21 pubmed
    ..Therefore, the possibility exists that normal tarsus determination is HOX independent. ..
  42. Roy S, Sen S. Homology modeling based solution structure of Hoxc8-DNA complex: role of context bases outside TAAT stretch. J Biomol Struct Dyn. 2005;22:707-18 pubmed
    ..The predictions based on the model are also amenable to experimental verification. ..
  43. Gutmanas A, Billeter M. Specific DNA recognition by the Antp homeodomain: MD simulations of specific and nonspecific complexes. Proteins. 2004;57:772-82 pubmed
    ..The shift from a water-dominated to a more "dry" interface may prove important in the design of proteins binding DNA in a specific manner. ..
  44. Qian Y, Otting G, Furukubo Tokunaga K, Affolter M, Gehring W, Wuthrich K. NMR structure determination reveals that the homeodomain is connected through a flexible linker to the main body in the Drosophila Antennapedia protein. Proc Natl Acad Sci U S A. 1992;89:10738-42 pubmed
  45. Adamson A, Shearn A. Molecular genetic analysis of Drosophila ash2, a member of the trithorax group required for imaginal disc pattern formation. Genetics. 1996;144:621-33 pubmed
    ..On immunoblots these affinity-purified antibodies detect a 70-kDa protein in larvae and a 53-kDa protein in pupae. ..
  46. Le S, Maizel J. A common RNA structural motif involved in the internal initiation of translation of cellular mRNAs. Nucleic Acids Res. 1997;25:362-69 pubmed
    ..We suggest that the common RNA structural motif conserved in the diverse BiP and FGF-2 mRNAs has a general function in the internal ribosome binding mechanism of cellular mRNAs. ..
  47. Schubert F, Nieselt Struwe K, Gruss P. The Antennapedia-type homeobox genes have evolved from three precursors separated early in metazoan evolution. Proc Natl Acad Sci U S A. 1993;90:143-7 pubmed
    ..These genes later independently gave rise to the 13 groups of paralogous genes in vertebrates and to the 11 Antennapedia-type genes in the Drosophila complexes. ..
  48. Burlina F, Sagan S, Bolbach G, Chassaing G. Quantification of the cellular uptake of cell-penetrating peptides by MALDI-TOF mass spectrometry. Angew Chem Int Ed Engl. 2005;44:4244-7 pubmed
  49. Prince F, Katsuyama T, Oshima Y, Plaza S, Resendez Perez D, Berry M, et al. The YPWM motif links Antennapedia to the basal transcriptional machinery. Development. 2008;135:1669-79 pubmed publisher
    ..BIP2 is a TATA-binding protein associated factor (also known as dTAFII3) that links ANTP to the basal transcriptional machinery. ..
  50. Terol J, Perez Alonso M, De Frutos R. Molecular characterization of the zerknüllt region of the Antennapedia complex of D. subobscura. Chromosoma. 1995;103:613-24 pubmed
    ..melanogaster and for D. pseudoobscura. Finally, we present cytological evidence showing that the ANT-C is inverted in D. subobscura as compared to D. melanogaster. ..
  51. Oh S, Sarnow P. Gene regulation: translational initiation by internal ribosome binding. Curr Opin Genet Dev. 1993;3:295-300 pubmed
  52. Schwartz J, Zhang S. Peptide-mediated cellular delivery. Curr Opin Mol Ther. 2000;2:162-7 pubmed
    ..A fundamentally new property of these moieties will allow the therapeutic intervention in the biochemistry of the target cell without the need to alter its genome. ..
  53. Ohtsuki S, Levine M, Cai H. Different core promoters possess distinct regulatory activities in the Drosophila embryo. Genes Dev. 1998;12:547-56 pubmed
    ..These results provide in vivo evidence that different core promoters possess distinct regulatory activities. We discuss the possibility that an invariant TFIID complex can adopt different conformations on the core promoter. ..