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Gene Review

Antp  -  Antennapedia

Drosophila melanogaster

Synonyms: 3.4, ANT-C, ANT-P, ANTC, ANTP, ...
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Disease relevance of Antp

  • The homeodomain encoded by the Antennapedia (Antp) gene of Drosophila was overproduced in a T7 expression vector in Escherichia coli [1].
  • Instead, it mimics Antp in directing T2 denticle pattern, and it can rescue the cuticular loss-of-function phenotype of Antp mutants [2].
  • Protein transduction domains (PTDs), such as the third helix of the Drosophila Antennapedia homeobox gene (Antp) and the HIV TAT PTD, possess a characteristic positive charge on the basis of their enrichment for arginine and lysine residues [3].
  • Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency [4].
  • Fusion of W45 to membrane translocation signals from HIV-1 tat protein (YGRKKRRQRRRPP-LRK(5)H, DT-2) or Drosophila Antennapedia homeo-domain (RQIKIWFQNRRMKWKK-LRK(5)H, DT-3) proved to be an efficient method for intracellular delivery of these highly charged peptides [5].

Psychiatry related information on Antp

  • We suggest that Ns-protein deficiency, reduced cAMP levels, or both, are involved in the mental deficiency in these patients and probably in mental function in humans [4].

High impact information on Antp

  • In head and thorax the Ubx product overrides Sex combs reduced, Antennapedia, and probably other homeotic genes and dictates its own developmental program [6].
  • Here we describe a cotransfection assay in cultured D. melanogaster cells that is used to demonstrate that Ubx proteins (UBX) can repress an Antp promoter fusion and activate a Ubx promoter fusion, activities predicted from genetic studies [7].
  • A TAA-rich DNA sequence to which the Antp protein binds in vitro is sufficient to confer regulation on a heterologous promoter [8].
  • Sequences downstream of the Antp P1 and Ultrabithorax transcription start sites mediate the observed activation [8].
  • Using a cotransfection assay, we have shown that homeodomain proteins encoded by the homeotic gene Antennapedia (Antp) and the segmentation gene fushi tarazu, as well as a hybrid homeodomain protein, are activators of transcription from specific promoters in cultured Drosophila cells [8].

Biological context of Antp

  • The protein binds tightly to sequences near its own promoter and near the P1 promoter of Antenna-pedia (Antp), a homeotic gene Ubx is known to repress from genetic studies [9].
  • The binding sites occur in clusters downstream of the transcription start sites, and far upstream at Antp P1 [9].
  • The time course of the interaction and reporter gene fusion experiments suggests (but does not prove) a direct interaction between Antp and cis-regulatory elements of salm [10].
  • To obtain a more comprehensive view of how individual enhancers selectively interact with appropriate target genes, we used bioinformatic methods to identify new cis-regulatory DNAs in the approximately 50-kb Scr-Antp interval [11].
  • We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable [12].

Anatomical context of Antp

  • Antp is expressed in the nuclei of cells of the thoracic embryonic epidermis and several segments of the ventral and peripheral nervous systems [13].
  • Antp activates tsh in anterior midgut mesoderm [14].
  • We have sequenced the region containing the homeotic selector genes required for proper development of the head and anterior thorax, which is the counterpart of the ANTC in Drosophila [15].
  • Three observations rule out a cell autonomous role for ANTP in tarsus determination [16].
  • This hypothesis was tested by inserting the complementary DNA encoding the normal Antp protein into a heat-shock expression vector and subsequent germ-line transformation [17].

Associations of Antp with chemical compounds

  • These experiments indicate that the ninth amino acid of the recognition helix of the homeodomain, which is glutamine in all four of these Antp-type homeodomain proteins, is not sufficient to determine their DNA binding specificities [18].
  • Despite the hydrophobic nature of this tetrapeptide motif, the N-terminal arm consisting of residues -14 to 6 is flexibly disordered, and the well-defined part of the HD structure with residues 7-59 is indistinguishable from that of the shorter Antp HD polypeptide (where positions 0, 1, and 67 are methionine, arginine, and glycine, respectively) [19].
  • This hypoactive form of ANTP, but not the alanine-substituted form, is also reduced in its ability to bind to DNA cooperatively with the homeodomain protein Extradenticle [20].
  • The mobility shift assay was used to study the competition of the minor groove binder distamycin A with either an Antennapedia homeodomain (Antp HD) peptide or derivatives of a fushi tarazu homeodomain (ftz HD) peptide for their AT-rich DNA binding site [21].
  • Exposure of Ns and ssa40a larvae to half-lethal concentrations of 5-bromodeoxyuridine (BUdR) and flourouracil (FU) together or separately during the presumptive time of gene action suppresses the expressivity and penetrance of the mutants [22].

Physical interactions of Antp

  • The three Hox genes of the Bithorax Complex as well as Antennapedia (Antp) have been shown to be expressed in the posterior cardiac tube, while no Hox gene is expressed in the anterior aorta [23].
  • Restriction fragments containing ftz homeodomain binding sites were identified within a 90 kb stretch of DNA extending the Antp P1 and P2 promoters [24].
  • We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes [25].

Regulatory relationships of Antp

  • Taken together, these data indicate that hth is an antennal selector gene, and that Antp promotes leg development by repressing hth and consequently nuclear Exd [26].
  • Therefore, we conclude that Antp negatively regulates salm [10].
  • The good correlation between the in vitro DNA binding preferences of these four Antp-type homeodomain proteins and their ability to specifically regulate a Dfd enhancer element in the embryo, suggests that the modest binding differences that distinguish them make an important contribution to their unique regulatory specificities [18].
  • In the epidermis, Antp has been shown to negatively regulate Scr, but it positively regulates Scr in the visceral mesoderm [27].
  • We have mapped the cis-acting control sequences of the homeotic Antennapedia (Antp) gene regulated by Pc [28].

Other interactions of Antp

  • Here we assess the functional significance of some of these interactions by expressing the Antp, Ubx or both homoeotic genes under the control of the heat-shock promoter [29].
  • Third, Antp is a repressor of hth [26].
  • First, removing the function of exd or hth, which is required for the nuclear localization of Exd protein, transforms the antenna into leg; such transformations occur without activation of Antp [26].
  • Here we show that mutations in several of the gap genes strongly alter the early patterns of Antp and Abd-B expression [30].
  • DNA from each of these 3' exons also hybridized weakly to DNA from the fushi tarazu locus of the ANT-C [31].
  • BIP2 is a TATA-binding protein associated factor (also known as dTAFII3) that links ANTP to the basal transcriptional machinery [32].

Analytical, diagnostic and therapeutic context of Antp


  1. Isolation and sequence-specific DNA binding of the Antennapedia homeodomain. Müller, M., Affolter, M., Leupin, W., Otting, G., Wüthrich, K., Gehring, W.J. EMBO J. (1988) [Pubmed]
  2. Activity regulation of Hox proteins, a mechanism for altering functional specificity in development and evolution. Li, X., McGinnis, W. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Characterization of a class of cationic peptides able to facilitate efficient protein transduction in vitro and in vivo. Mi, Z., Mai, J., Lu, X., Robbins, P.D. Mol. Ther. (2000) [Pubmed]
  4. Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency. Farfel, Z., Friedman, E. Ann. Intern. Med. (1986) [Pubmed]
  5. Highly specific, membrane-permeant peptide blockers of cGMP-dependent protein kinase Ialpha inhibit NO-induced cerebral dilation. Dostmann, W.R., Taylor, M.S., Nickl, C.K., Brayden, J.E., Frank, R., Tegge, W.J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. The developmental effect of overexpressing a Ubx product in Drosophila embryos is dependent on its interactions with other homeotic products. González-Reyes, A., Morata, G. Cell (1990) [Pubmed]
  7. Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells. Krasnow, M.A., Saffman, E.E., Kornfeld, K., Hogness, D.S. Cell (1989) [Pubmed]
  8. Transcriptional activation by the Antennapedia and fushi tarazu proteins in cultured Drosophila cells. Winslow, G.M., Hayashi, S., Krasnow, M., Hogness, D.S., Scott, M.P. Cell (1989) [Pubmed]
  9. An Ultrabithorax protein binds sequences near its own and the Antennapedia P1 promoters. Beachy, P.A., Krasnow, M.A., Gavis, E.R., Hogness, D.S. Cell (1988) [Pubmed]
  10. Identification of target genes of the homeotic gene Antennapedia by enhancer detection. Wagner-Bernholz, J.T., Wilson, C., Gibson, G., Schuh, R., Gehring, W.J. Genes Dev. (1991) [Pubmed]
  11. Long-range enhancer-promoter interactions in the Scr-Antp interval of the Drosophila Antennapedia complex. Calhoun, V.C., Levine, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Homeotic response elements are tightly linked to tissue-specific elements in a transcriptional enhancer of the teashirt gene. McCormick, A., Coré, N., Kerridge, S., Scott, M.P. Development (1995) [Pubmed]
  13. The localization and regulation of Antennapedia protein expression in Drosophila embryos. Carroll, S.B., Laymon, R.A., McCutcheon, M.A., Riley, P.D., Scott, M.P. Cell (1986) [Pubmed]
  14. Role of the teashirt gene in Drosophila midgut morphogenesis: secreted proteins mediate the action of homeotic genes. Mathies, L.D., Kerridge, S., Scott, M.P. Development (1994) [Pubmed]
  15. Sequence of the Tribolium castaneum homeotic complex: the region corresponding to the Drosophila melanogaster antennapedia complex. Brown, S.J., Fellers, J.P., Shippy, T.D., Richardson, E.A., Maxwell, M., Stuart, J.J., Denell, R.E. Genetics (2002) [Pubmed]
  16. Tarsus determination in Drosophila melanogaster. Percival-Smith, A., Teft, W.A., Barta, J.L. Genome (2005) [Pubmed]
  17. Redesigning the body plan of Drosophila by ectopic expression of the homoeotic gene Antennapedia. Schneuwly, S., Klemenz, R., Gehring, W.J. Nature (1987) [Pubmed]
  18. Antp-type homeodomains have distinct DNA binding specificities that correlate with their different regulatory functions in embryos. Dessain, S., Gross, C.T., Kuziora, M.A., McGinnis, W. EMBO J. (1992) [Pubmed]
  19. NMR structure determination reveals that the homeodomain is connected through a flexible linker to the main body in the Drosophila Antennapedia protein. Qian, Y.Q., Otting, G., Furukubo-Tokunaga, K., Affolter, M., Gehring, W.J., Wüthrich, K. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. Jaffe, L., Ryoo, H.D., Mann, R.S. Genes Dev. (1997) [Pubmed]
  21. Distamycin-induced inhibition of homeodomain-DNA complexes. Dorn, A., Affolter, M., Müller, M., Gehring, W.J., Leupin, W. EMBO J. (1992) [Pubmed]
  22. Inhibition of two homeotic mutants of Drosophila by 5-bromodeoxyuridine and fluorouracil. Ibars, G.C., Selick, H.E., Kauffman, S.A. J. Exp. Zool. (1981) [Pubmed]
  23. Drosophila cardiac tube organogenesis requires multiple phases of Hox activity. Perrin, L., Monier, B., Ponzielli, R., Astier, M., Semeriva, M. Dev. Biol. (2004) [Pubmed]
  24. The interaction of proteins encoded by Drosophila homeotic and segmentation genes with specific DNA sequences. Laughon, A., Howell, W., Scott, M.P. Development (1988) [Pubmed]
  25. The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription. Vázquez, M., Moore, L., Kennison, J.A. Development (1999) [Pubmed]
  26. Control of antennal versus leg development in Drosophila. Casares, F., Mann, R.S. Nature (1998) [Pubmed]
  27. Expression and function of the homoeotic genes Antennapedia and Sex combs reduced in the embryonic midgut of Drosophila. Reuter, R., Scott, M.P. Development (1990) [Pubmed]
  28. Direct interaction of the Polycomb protein with Antennapedia regulatory sequences in polytene chromosomes of Drosophila melanogaster. Zink, B., Engström, Y., Gehring, W.J., Paro, R. EMBO J. (1991) [Pubmed]
  29. Are cross-regulatory interactions between homoeotic genes functionally significant? González-Reyes, A., Urquia, N., Gehring, W.J., Struhl, G., Morata, G. Nature (1990) [Pubmed]
  30. Gap genes define the limits of antennapedia and bithorax gene expression during early development in Drosophila. Harding, K., Levine, M. EMBO J. (1988) [Pubmed]
  31. Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. Scott, M.P., Weiner, A.J. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  32. The YPWM motif links Antennapedia to the basal transcriptional machinery. Prince, F., Katsuyama, T., Oshima, Y., Plaza, S., Resendez-Perez, D., Berry, M., Kurata, S., Gehring, W.J. Development (2008) [Pubmed]
  33. Regulation of Antennapedia transcript distribution by the bithorax complex in Drosophila. Hafen, E., Levine, M., Gehring, W.J. Nature (1984) [Pubmed]
  34. Identification of planarian homeobox sequences indicates the antiquity of most Hox/homeotic gene subclasses. Balavoine, G., Telford, M.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  35. Cloning and expression of rat homeo-box-containing sequences. Falzon, M., Sanderson, N., Chung, S.Y. Gene (1987) [Pubmed]
  36. Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy. Phillips, C.L., Vershon, A.K., Johnson, A.D., Dahlquist, F.W. Genes Dev. (1991) [Pubmed]
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