The structure and function of the homeodomain

Scott, Matthew P.; Tamkun, John W.; Hartzell, George W.

doi:10.1016/0304-419x(89)90033-4

Cited by 625 publications

(645 citation statements)

References 127 publications

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“…In adults, the mRNA and protein have also been detected in some tissues, including liver, lung, kidney, and central nervous system (Odenwald et al 1987;Garbem et al 1989). DNA-binding assays showed that Hox-l.3 high-affinity binding sites contain an ATTA core motif , which is also the core of Drosophila Antp class high-affinity binding sites (for review, see Scott et al 1989). Nevertheless, the biological function of Hox-1.3 is unknown.…”

mentioning

confidence: 99%

The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene.

Zhao¹,

Lazzarini²,

Pick³

1993

Genes Dev.

109

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mentioning

confidence: 99%

The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene.

Zhao¹,

Lazzarini²,

Pick³

1993

Genes Dev.

109

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“…It is now recognized that the homeo domain is a DNA-binding motif of -61 residues found in many transcriptional regulators {for review, see Hayashi and Scott 1990). There are >90 known members of the homeo domain superfamily, many with extremely similar amino acid sequences {Scott et al 1989). This conservation can extend between species; for example, the Drosophila Antennapedia (Antp) homeo domain is identical to the mouse Hox-1.1 borneo domain at 56 of 61 positions.…”

mentioning

confidence: 99%

Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy.

Phillips¹,

Vershon²,

Johnson³

et al. 1991

Genes Dev.

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The yeast a2 protein is a regulator of cell type in Saccharomyces cerevisiae. It represses transcription of a set of target genes by binding to an operator located upstream of each of these genes. The c~2 protein shares weak sequence similarity with members of the homeo domain family; the homeo domain is a 60-amino-acid segment found in many eukaryotic transcriptional regulators. In this paper we address the question of whether ~2 is structurally related to prototypical members of the homeo domain family. We used solution ~H and lSN nuclear magnetic resonance (NMR) spectroscopy to determine the secondary structure of an 83-amino-acid residue fragment of ~2 that contains the homeo domain homology. We have obtained resonance assignments for the backbone protons and nitrogens of the entire 60-residue region of the putative homeo domain and for most of the remainder of the ,Y2 fragment. The secondary structure was determined by using NOE connectivities between backbone protons, 3J~N_H. coupling constants, and dynamical information from the hydrogen exchange kinetics of the backbone amides. Three helical segments exist in the c~2 fragment consisting of residues 11-23, 32-42, and 46-60 (corresponding to residues 138-150, 159-169, and 173-187 of the intact protein). The positions of these three helices correspond extremely well to those of the Drosophila Antennapedia (Antp) and engrailed (en) homeo domains, whose three-dimensional structures have recently been determined by NMR spectroscopy and X-ray crystallography, respectively. This study reveals that in spite of low sequence similarity between the homeo domain of a2 and that of higher eukaryotes, the secondary structures of these proteins are well conserved.

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“…Similarly to optimal peptide substrates for Abl, Fps and Src protein tyrosine kinases [39], THRP contains several tyrosine residues. Interestingly, the basic N-terminal region of THRP exhibits 40-50 % similarity over a 53-residue stretch to the DNA-binding region of homeodomain proteins [40][41][42]. Homeodomain proteins have been implicated in specifying positional information in the embryo during development and in the control of cell lineages by regulating the expression of cell type-specific genes…”

Section: Speciesmentioning

confidence: 99%

“…The 6.5 kb mRNA seen was not THR. [41]. Noteworthy is the observation that all of the residues in the homeodomain that are implicated in contacting the DNA major groove are conserved in the basic region of THRP.…”

Section: Figure 3 Representative Northern Blot Analysis Of Thr Mrnamentioning

confidence: 99%

Cloning and characterization of a complementary DNA for a thyroid hormone-responsive protein in mature rat cerebral tissue

Shah

Schneiderjohn

et al. 1997

Biochemical Journal

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A gene responsive to thyroid hormone (TH) has been identified in the adult rat brain cerebral tissue. A cDNA probe differentially expressed in euthyroid, hypothyroid and hyperthyroid rat cerebral tissue, generated by reverse transcriptase-PCR differential display of mRNA, was used to screen the rat brain cDNA library. A 3.4 kb positive clone hybridized in Northern blots with a 3.8 kb mRNA that proved to be TH responsive (THR). The remaining coding sequence and a part of the 5ʹ untranslated region of this cDNA were obtained by 5ʹ rapid amplification of cDNA ends. The deduced amino acid sequence revealed that THR protein (THRP), a 68 kDa moiety, has 83% sequence similarity with c-Abl interactor protein (Abi-2), which is a substrate for tyrosine kinase activity of c-Abl. The extensive similarity between the two proteins suggests a potential role for THRP as a substrate for c-Abl. Northern analysis showed that the expression of THR mRNA in hyperthyroid rats is 6-fold that in euthyroid rats. There is also a 4-6-fold increase in the concentration of THRP, as analysed by Western analysis. Owing to the extensive similarity between rat THRP and human Abi-2, a polyclonal anti- (human Abi-2) antibody was successfully used for Western analysis of proteins from the rat tissues. The observed increase in both the mRNA and the protein did not decline after β-adrenergic system blockade with propranolol, suggesting that the action of TH on the expression of this gene is not mediated through the β-adrenergic system. Immunohistochemical studies revealed that neuronal cells were particularly rich in THRP. Both THR mRNA and THRP are rapidly induced in vivo after intravenous administration of thyroxine. Tissue distribution studies indicated that the cerebral tissue was particularly enriched with THR mRNA and 68 kDa THRP. A cDNA clone for a THR gene could provide a useful tool to study the molecular mechanisms of TH effects on cerebral tissue in adult animals.

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The structure and function of the homeodomain

Cited by 625 publications

References 127 publications

The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene.

The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene.

Secondary structure of the homeo domain of yeast alpha 2 repressor determined by NMR spectroscopy.

Cloning and characterization of a complementary DNA for a thyroid hormone-responsive protein in mature rat cerebral tissue

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