Patent Publication Number: US-2002001824-A1

Title: Ligand-gated anion channels of insects

Description:
FIELD OF THE INVENTION  
       [0001] The invention relates to ligand-gated anion channels of insects. More particularly, the invention relates to polypeptides which constitute novel subunits of ligand-gated anion channels of insects, to nucleic acids (also referred to as polynucleotides) encoding these polypeptides, and, in particular, to their use for finding active compounds for crop protection.  
       BACKGROUND OF THE INVENTION  
       [0002] Ligand-gated anion channels, such as, for example, the chloride-dependent GABA receptor or the glutamate receptor, play an important role in neurotransmission in the animal kingdom. Binding of the ligand to the receptor causes temporary opening of the channel and allows the flux of anions through it. It is assumed that a receptor is composed of five subunits grouped around a pore. Each of these subunits is a protein composed of an extracellular N-terminal portion, followed by three transmembrane regions, an intracellular portion, and a fourth transmembrane region and a short extracellular C-terminal portion (Hosie et al., 1997).  
       [0003] In insects, GABA and glutamate are the most important inhibitory neurotransmitters of the central nervous system (Cleland, 1996; Delgado et al., 1989). Accordingly, GABA and glutamate receptors can be detected electrophysiologically on preparations of central ganglia of insects. These receptors are, moreover, the molecular target of important natural and synthetic insecticides (Sattelle, 1990, 1992; Cully et al., 1994, 1996; Arena et al., 1995), which act as agonists (for example avermectin) and antagonists (for example fipronil) of ligand-gated anion channels. In addition the absence of the chloride-dependent glutamate receptor in higher animals (vertebrates) emphasizes its outstanding importance as a selective target.  
       [0004] The protein sequence of a number of chloride-dependent GABA and glutamate receptors of insects is already known. Thus, for example, the sequences of three different GABA receptor subunits and of a glutamate receptor subunit have been described for  Drosophila melanogaster  (ffrench-Constant et al., 1991; Harvey et al., 1994; Henderson et al., 1993; Cully et al., 1996).  
       [0005] Providing new subunits of ligand-gated anion channels from insects is of great practical importance, for example, for the search for new insecticides, particularly interesting ligand-gated anion channels being those which differ to a greater extent from the known ones than is the case between functional homologues.  
       SUMMARY OF THE INVENTION  
       [0006] Polypeptides of the present invention are involved in the synthesis of ligand-gated anion channels. Polynucleotides which encode the polypeptides may be used to form DNA constructs, vectors, host cells and transgenic invertebrates. 
     
    
    
     DETAILED DESCRIPTION  
     [0007] The present invention is therefore based in particular on the object of providing subunits of ligand-gated anion channels of insects and assay systems based thereon with a high throughput of compounds to be assayed (High Throughput Screening Assays; HTS assays).  
     [0008] The object is achieved by providing polypeptides which form part of a ligand-gated anion channel and comprise an amino acid sequence which has at least 70% identity, preferably at least 80% identity, especially preferably at least 90% identity, very especially preferably at least 95% identity, with a sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16 or 18 over a length of at least 20, preferably at least 25, especially preferably at least 30, consecutive amino acids and very especially preferably over their entire lengths.  
     [0009] The degree of identity of the amino acid sequences is preferably determined with the aid of the GAP program of the GCG package, Version 9.1, using standard settings (Devereux et al., 1984).  
     [0010] The term “polypeptides”, as used herein refers not only to short amino acid chains, which are usually termed peptides, oligopeptides or oligomers, but also to longer amino acid chains which are usually termed proteins. It encompasses amino acid chains which can be modified either by natural processes, such as post-translational processing, or by prior-art chemical methods. Such modifications may occur at different sites and repeatedly in a polypeptide, such as, for example, at the peptide backbone, at the amino acid side chain, at the amino and/or at the carboxyl terminus. They comprise, for example, acetylations, acylations, ADP-ribosylations, amidations, covalent linkages with flavins, haem moieties, nucleotides or nucleotide derivatives, lipids or lipid derivatives or phosphatidylinositol, cyclizations, disulphide bridge formations, demthylations, cystine formations, formylations, gamma-carboxylations, glycosylations, hydroxylations, iodinations, methylations, myristoylations, oxidations, proteolytic processings, phosphorylations, selenoylations and tRNA-mediated additions of amino acids.  
     [0011] The polypeptides according to the invention may exist in the form of “mature” proteins or as parts of larger proteins, for example as fusion proteins. They may furthermore exhibit secretion or leader sequences, pro-sequences, sequences which make possible simple purification, such as multiple histidine residues, or additional stabilizing amino acids.  
     [0012] A functional ligand-gated anion channel is preferably achieved by homo- or heteromerization of the polypeptides according to the invention.  
     [0013] The polypeptides according to the invention need not exhibit the length of naturally occurring anion channel subunits, but may also just be fragments thereof as long as they retain the ability of forming functional ligand-gated anion channels. Anion channels which, in comparison with channels composed of the polypeptides according to the invention with an amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16 or 18, exert an activity which is increased or reduced by 50% are still considered as according to the invention. In this context, it is not necessary that the polypeptides according to the invention can be derived from ligand-gated anion channels of  Drosophila melanogaster.  Polypeptides which correspond to ligand-gated anion channels of, for example, the following invertebrates, or to fragments thereof which retain the ability of exerting the biological activity of these channels, are also considered as according to the invention: insects, nematodes, arthropods, molluscs.  
     [0014] In comparison with the corresponding region of naturally occurring ligand-gated anion channels, the polypeptides according to the invention may exhibit deletions or amino acid substitutions as long as they retain the ability of forming functional channels. Conservative substitutions are preferred. Such conservative substitutions encompass variations, one amino acid being replaced by another amino acid from amongst the following group:  
     [0015] 1. Small aliphatic residues, unpolar residues or residues of little polarity: Ala, Ser, Thr, Pro and Gly;  
     [0016] 2. Polar, negatively charged residues and amides: Asp, Asn, Glu and Gln;  
     [0017] 3. Polar, positively charged residues: His, Arg and Lys;  
     [0018] 4. Large aliphatic unpolar residues: Met, Leu, Ile, Val and Cys; and  
     [0019] 5. Aromatic residues: Phe, Tyr and Trp.  
     [0020] Preferred conservative substitutions can be seen from the following list:  
                                   Original residue   Substitution                  Ala   Gly, Ser       Arg   Lys       Asn   Gln, His       Asp   Glu       Cys   Ser       Gln   Asn       Glu   Asp       Gly   Ala, Pro       His   Asn, Gln       lle   Leu, Val       Leu   Ile, Val       Lys   Arg, Gln, Glu       Met   Leu, Tyr, Ile       Phe   Met, Leu, Tyr       Ser   Thr       Thr   Ser       Trp   Tyr       Tyr   Trp, Phe       Val   Ile, Leu                  
 
     [0021] The term “functional ligand-gated anion channel” or “functional channel” as used herein refers to an anion channel which, after binding a ligand, becomes permeable to anions.  
     [0022] The subject-matter of the present invention further includes ligand-gated anion channels composed of the polypeptides according to the invention.  
     [0023] Preferred embodiments of the polypeptides according to the invention are those polypeptides which form part of ligand-gated anion channels of  Drosophila melanogaster  and which have an amino acid sequence of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16 or 18.  
     [0024] The present invention also relates to nucleic acid which encode the polypeptides according to the invention.  
     [0025] The nucleic acids according to the invention are, in particular, single-stranded or double-stranded deoxyribonucleic acids (DNA) or ribonucleic acids (RNA). Preferred embodiments are fragments of genomic DNA which may contain introns, and cDNAs.  
     [0026] cDNAs which have a nucleotide sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15 or 17 constitute preferred embodiments of the nucleic acid according to the invention.  
     [0027] The present invention also encompasses nucleic acids which hybridize under stringent conditions with sequences of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15 or 17.  
     [0028] The term “to hybridize” as used in the present context describes the process during which a single-stranded nucleic acid molecule undergoes base pairing with a complementary strand. Starting from the sequence information disclosed herein, this allows, for example, DNA fragments to be isolated from insects other than  Drosophila melanogaster  which encode subunits of ligand-gated anion channels.  
     [0029] Preferred hybridization conditions are stated hereinbelow: Hybridization solution: 6X SSC/0% formamide, preferred hybridization solution: 6X SSC/25% formamide Hybridization temperature: 34° C., preferred hybridization temperature: 42° C. Wash step 1:2X SSC at 40° C., Wash step 2:2X SSC at 45° C.; preferred wash step 2. 0,6X SSC at 55° C.;  
     [0030] especially preferred wash step 2: 0.3X SSC at 65° C.  
     [0031] The present invention furthermore encompasses nucleic acids which have at least 70% identity, preferably at least 80% identity, especially preferably at least 90% identity, very especially preferably at least 95% identity, with a sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15 or 17 over a length of at least 20, preferably at least 25, especially preferably at least 30, consecutive nucleotides, and very especially preferably over their full length.  
     [0032] The degree of identity of the nucleic acid sequences is preferably determined with the aid of the program GAP from the package GCG, Version 9.1, using standard settings.  
     [0033] The sequences in accordance with the Genbank Accession Nos. AC002502, AF145639 and AC004420 are incorporated into the present description by reference.  
     [0034] The present invention furthermore relates to DNA constructs which comprise a nucleic acid according to the invention and a heterologous promoter.  
     [0035] The term “heterologous promoter” as used in the present context refers to a promoter which has properties other than the promoter which controls the expression of the gene in question in the original organism. The term “promoter” as used in the present context generally refers to expression control sequences.  
     [0036] The choice of heterologous promoters depends on whether pro- or eukaryotic cells or cell-free systems are used for expression. Examples of heterologous promoters are the SV40 early or later promoter, the adenovirus early or late promoter or the cytomegalo virus early or late promoter, the lac system, the trp system, the main operator and promoter regions of phage lambda, the fd coat protein control regions, the 3-phosphoglycerate kinase promoter, the acid phosphatase promoter and the yeast α-mating factor promoter.  
     [0037] The invention furthermore relates to vectors which contain a nucleic acid according to the invention or a DNA construct according to the invention. All the plasmids, phasmids, cosmids, YACs or artificial chromosomes used in molecular biology laboratories can be used as vectors.  
     [0038] The present invention also relates to host cells containing a nucleic acid according to the invention, a DNA construct according to the invention or a vector according to the invention.  
     [0039] The term “host cell” as used in the present context refers to cells which do not naturally contain the nucleic acids according to the invention.  
     [0040] Suitable host cells are not only prokaryotic cells such as bacteria from the genera Bacillus, Pseudomonas, Streptomyces, Streptococcus, Staphylococcus, preferably  E. coli,  but also eukaryotic cells such as yeasts, mammalian cells, amphibian cells, insect cells or plant cells. Preferred eukaryotic host cells are HEK-293, Schneider S2, Spodoptera Sf9, Kc, CHO, COS1, COS7, HeLa, C127, 3T3 or BHK cells and, in particular, Xenopus oocytes.  
     [0041] The invention furthermore relates to antibodies which specifically bind to the abovementioned polypeptides or channels. Such antibodies are produced in the customary manner. For example, such antibodies may be produced by injecting a substantially immunocompetent host with such an amount of a polypeptide according to the invention or a fragment thereof which is effective for antibody production, and subsequently obtaining this antibody. Furthermore, an immortalized cell line which produces monoclonal antibodies may be produced in a manner known per se. If appropriate, the antibodies may be labelled with a detection reagent. Preferred examples of such a protection reagent are enzymes, radiolabelled elements, fluorescent chemicals or biotin. Instead of the complete antibody, fragments may also be employed which have the desired specific binding properties. The term “antibodies” as used in the present context therefore also extends to parts of complete antibodies, such as Fa, F(ab′) 2  or Fv fragments which are still capable of binding to the epitopes of the polypeptides according to the invention.  
     [0042] The nucleic acids according to the invention can be used, in particular, for generating transgenic invertebrates. These can be employed in assay systems which are based on an expression, of the polypeptides according to the invention, which deviates from the wild type. Based on the information disclosed herein, it is furthermore possible to generate transgenic invertebrates where expression of the polypeptides according to the invention is altered owing to the modification of other genes or promoters.  
     [0043] The transgenic invertebrates are generated, for example in the case of  Drosophila melanogaster,  by P-Element-mediated gene transfer (Hay et al., 1997) or, in  Caenorhabditis elegans,  by transposon-mediated gene transfer (for example by Tcl; Plasterk, 1996).  
     [0044] The invention thus also relates to transgenic invertebrates which contain at least one of the nucleic acids according to the invention, preferably transgenic invertebrates of the species  Drosophila melanogaster  or  Caenorhabditis elegans,  and to their transgenic progeny. The transgenic invertebrates preferably contain the polypeptides according to the invention in a form which deviates from the wild type.  
     [0045] The present invention furthermore relates to processes for producing the polypeptides according to the invention. Host cells which contain one of the nucleic acids according to the invention can be cultured under suitable conditions to produce the polypeptides encoded by the nucleic acids according to the invention. In doing this, the nucleic acid to be expressed may be adapted to the codon usage of the host cells. Thereupon, the desired polypeptides can be isolated from the cells or the culture medium in the customary manner. Polypeptides may also be produced in in vitro systems.  
     [0046] A rapid method of isolating the polypeptides according to the invention which are synthesized by host cells using a nucleic acid according to the invention starts with the expression of a fusion protein, it being possible for the fusion partner to be affinity-purified in a simple manner. For example, the fusion partner may be glutathione S-transferase. The fusion protein can then be purified on a glutathione affinity column. The fusion partner can then be removed by partial proteolytic cleavage, for example at linkers between the fusion partner and the polypeptide according to the invention to be purified. The linker can be designed such that it includes target amino acids such as arginine and lysine residues, which define sites for trypsin cleavage. To generate such linkers, standard cloning methods using oligonucleotides may be employed.  
     [0047] Other purification methods which are possible are based on preparative electrophoresis, FPLC, HPLC (for example using gel filtration, reversed-phase or moderately hydrophobic columns), gel filtration, differential precipitation, ion-exchange chromatography and affinity chromatography.  
     [0048] Since ligand-gated anion channels constitute membrane proteins, the purification methods preferably involve detergent extractions, for example using detergents which have no, or little, effect on the secondary and tertiary structures of the polypeptides, such as nonionic detergents.  
     [0049] The purification of the polypeptides according to the invention can encompass the isolation of membranes, starting from host cells which express the nucleic acids according to the invention. Such cells preferably express the polypeptides according to the invention in a sufficiently high copy number, so that the amount of polypeptide in a membrane fraction is at least 10 times higher than that found in comparable membranes of cells which naturally express ligand-gated anion channels; especially preferably, the amount is at least 100 times, very especially preferably at least 1000 times higher.  
     [0050] The terms “isolation or purification” as used in the present context mean that the polypeptides according to the invention are separated from other proteins or other macromolecules of the cell or of the tissue. The protein content of a composition containing the polypeptides according to the invention is preferably at least 10 times, especially preferably at least 100 times, higher than in a host cell preparation.  
     [0051] The polypeptides according to the invention may also be affinity-purified without a fusion partner with the aid of antibodies which bind to the polypeptides.  
     [0052] The present invention furthermore also relates to processes for the generation of the nucleic acids according to the invention. The nucleic acids according to the invention can be generated in the customary manner. For example, the complete nucleic acid molecules can be synthesized chemically. However, it is also possible to chemically synthesize only short sections of the sequences according to the invention, and such oligonucleotides can be radiolabelled or labelled with a fluorescent dye. The labelled oligonucleotides can be used for screening cDNA libraries generated starting from insect mRNA of for screening genomic libraries generated starting from insect genomic DNA. Clones which hybridize with the labelled oligonucleotides are chosen for isolating the DNA in question. After characterization of the DNA which has been isolated, the nucleic acids according to the invention are obtained in a simple manner.  
     [0053] Alternatively, the nucleic acids according to the invention can also be generated by means of PCR methods using chemically synthesized oligonucleotides.  
     [0054] The term “oligonucleotide(s)” as used in the present context denotes DNA molecules consisting of 10 to 50 nucleotides, preferably 15 to 30 nucleotides. They are synthesized chemically and can be used as probes.  
     [0055] The nucleic acids according to the invention allow new active compounds for crop protection and/or drugs for the treatment of humans and animals to be identified, such as chemicals which, being modulators, in particular agonists or antagonists, alter the properties of the ligand-gated anion channels according to the invention, to be identified. To this end, a recombinant DNA molecule comprising at least one nucleic acid according to the invention is introduced into a suitable host cell. The host cell is grown in the presence of a compound or a sample comprising a variety of compounds under conditions which allow expression of the receptors according to the invention. A change in the receptor properties can be detected as described hereinbelow in Example 2. This allows, for example, insecticidal substances to be found.  
     [0056] A functional ligand-gated anion channel can be detected by functionality assays or binding assays (Rudy et al., 1992). A functionality detection is, for example, the electrophysiological derivation of cells or oocytes which express ligand-gated anion channels and which respond to addition of ligands with an anion flux (which leads to changes in the potential at the cell membrane). Typically, the ligand-induced currents depend on the concentration of the ligand applied. Apart from the electrophysiological derivation, changes in the potential can also be visualized by, for example, potentiometric dyes. In a typical binding assay, potential agonists and antagonists are identified by their ability to displace known radiolabelled ligands from the channel. Examples of suitable known ligands are GABA, glutamate, glycine, muscimol, EBOB (n-propylethynyl bicycloorthobenzoate), BIDN (3,3-bis(trifluoromethyl)bicyclo-[2,2,1]heptane-2,2-dicarbonitrile), avermectin, fipronil.  
     [0057] Such assays can be used for finding agonists, antagonists or modulators in High Throughput Screening (HTS).  
     [0058] The term “agonist” as used in the present context refers to a molecule which activates ligand-gated anion channels.  
     [0059] The term “antagonist” as used in the present context refers to a molecule which displaces an agonist from its binding site.  
     [0060] The term “modulator” as used in the present invention constitutes the generic term for agonist and antagonist. Modulators can be small organochemical molecules, peptides or antibodies which bind to the polypeptides according to the invention. Further modulators may be small organochemical molecules, peptides or antibodies which bind to a molecule which, in turn, binds to the polypeptides according to the invention, thus influencing their biological activity. Modulators may constitute mimetics of natural substrates and ligands.  
     [0061] The modulators are preferably small organochemical compounds.  
     [0062] The binding of the modulators to the polypeptides according to the invention can alter the cellular processes in a manner which leads to the death of the insects treated therewith.  
     [0063] The present invention therefore also extends to the use of modulators of the polypeptides according to the invention or of the ligand-gated anion channels according to the invention as insecticides.  
     [0064] The nucleic acids according to the invention also allow compounds to be found which bind to the channels according to the invention. Again, they can be applied to plants as insecticides. For example, host cells which contain the nucleic acids according to the invention which express the corresponding channels or polypeptides, or the gene products themselves, are brought into contact with a compound or a mixture of compounds under conditions which permit the interaction of at least one compound with the host cells, the channels or the individual polypeptides.  
     [0065] Using host cells or transgenic invertebrates which contain the nucleic acids according to the invention, it is also possible to find substances which alter channel expression.  
     [0066] The above-described nucleic acids, vectors and regulatory regions according to the invention can furthermore be used for finding genes which encode polypeptides which are involved in the synthesis, in insects, of functionally similar ligand-gated anion channels. Functionally similar receptors are to be understood as meaning, in accordance with the present invention, channels which comprise polypeptides which, while differing from the amino acid sequence of the polypeptides described herein, essentially have the same functions.  
     [0067] Information on the sequence listing and on the figures:  
     [0068] SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15 and 17 show the nucleotide and amino acid sequences of the isolated ligand-gated anion channel cDNAs. SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16 and 18 furthermore show the amino acid sequences of the polypeptides deduced from the ligand-gated anion channel cDNA sequences.  
     EXAMPLES  
     Example 1  
     [0069] Isolation of the above-described polynucleotides  
     [0070] Polynucleotides were manipulated by standard methods of recombinant DNA technology (Sambrook et al., 1989). Nucleotide and protein sequences were bioinformatically processed using the package GCG Version 9.1 (GCG Genetics Computer Group, Inc., Madison Wis., U.S.A.).  
     Example 2  
     [0071] Generation of the expression constructs  
     [0072] The sequence regions of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15 and 17 were amplified by means of polymerase chain reaction (PCR) and cloned into the vectors pcDNA3.1/Neo(lnvitrogen, Groningen) and plE1-¾ (Novagen, Madison Wis., U.S.A.).  
     [0073] Heterologous expression  
     [0074] The ligand-gated anion channels from insects were expressed functionally in Sf9 cell lines and Xenopus oocytes. To this end, expression vectors with the various subunits were introduced into the cells/oocytes individually and in various combinations.  
     [0075] Measurements in Sf9 cells  
     [0076] 1. Cell culture  
     [0077] Sf9 cells were grown in 50 ml CELLSTAR cell culture flasks(Greiner, Nürtingen, Germany) at 26° C. in 5 ml of SF-900 II cell culture medium supplemented with L-glutamine (Gibco BRL, Karlsruhe, Germany).  
     [0078] 2. Transfection  
     [0079] For transfection, 1×10 5  cells were seeded per well of a 4-well NUNCLON cell culture dish (Nunc, Wiesbaden, Germany). Transfection was carried out with FuGENE 6 (Roche Molecular Biochemicals, Mannheim, Germany), following standard protocols. 1 μg of vector DNA was used per expression construct. The electrophysiological measurement was carried out 26 to 48 hours after transfection.  
     [0080] Oocyte measurements  
     [0081] 1. Oocyte preparation the oocytes were obtained from an adult female Xenopus laevis from (Horst Khler, Hamburg, Germany). The frogs were kept in large tanks with circulating water at a water temperature of 20-24° C. Parts of the frog ovary were removed through a small incision in the abdomen (approx. 1 cm), with full anaesthesia. The ovary was then treated for approximately 140 minutes with 25 ml of collagenase (type l, , C-0130, SIGMA-ALDRICH CHEMIE GmbH, Deisenhofen, Germany; 355U/ml, prepared with Barth&#39;s solution without calcium in mM: NaCl 88, KCl 1, MgSO4 0.82, NaHCO3 2.4, Tris/HCl 5, pH7.4), with constant shaking. Thereupon, the oocytes were washed with Barth&#39;s solution without calcium. Only oocytes at maturity stage V (Dumont, 1972) were selected for the further treatment and transferred into microtitre plates (Nunc MicroWell™ plates, cat. No. 245128+263339 (lid), Nunc GmbH &amp; Co. KG, Wiesbaden, Germany), filled with Barth&#39;s solution (in mM: NaCl 88, KCl 1, MgSO 4  0.82, Ca(NO 3 ) 2  0.33, CaCl 2  0.41, NaHCO3 2.4, Tris/HCl 5, pH7.4) and gentamicin (gentamicin sulphate, G-3632, SIGMA-ALDRICH CHEMIE GmbH, Deisenhofen, Germany; 100U/ml). Thereupon, the oocytes were stored at 19.2° C. in a cooling incubator (type KB 53, WTB Binder Labortechnik GmbH, Tuttlingen, Germany).  
     [0082] 2. Injecting the oocytes  
     [0083] Injection electrodes of diameter 10-15 μm, were prepared using a pipette-drawing device (type L/M-3P-A, List-electronic, Darmstadt-Eberstadt, Germany). Prior to injection, aliquots with the DNA were defrosted and diluted with water to a final concentration of 10 ng/μl. The DNA samples were centrifuged for 120 seconds at 3200 g (type Biofuge 13, Heraeus Instruments GmbH, Hanau, Germany). An extended PE tube was subsequently used as transfer tube to fill the pipettes from the rear end. The injection electrodes were attached to an X,Y,Z positioning system (treatment centre EP1090, isel-automation, Eiterfeld, Germany). With the aid of a Macintosh computer the oocytes in the microtitre plate wells were approached, and approximately 50 nl of the DNA solution were injected into the oocytes by briefly applying a pressure (0.5-3.0 bar, 3-6 seconds).  
     [0084] 3. Electrophysiological measurements  
     [0085] A two-electrode voltage terminal equipped with a TURBO TEC-10CD (npi electronic GmbH, Tamm, Germany) amplifier was used to carry out the electrophysiological measurements. The micropipettes required for this purpose were drawn in two movements from aluminium silicate glass (capillary tube, Art.-No. 14 630 29, l=100 mm, Ø ext =1.60 mm, Ø int =1.22 mm, Hilgenberg GmbH, Malsfeld, Germany) (Hamill et al., 1981). Current and voltage electrodes had a diameter of 1-3 μm and were filled with 1.5M KCl and 1.5M potassium acetate. The pipettes had a capacitance of 0.2-0.5 MW. To carry out the electrophysiological measurements, the oocytes were transferred into a small chamber which was flushed continuously with normal Rimland solution (in mM: KCl 90, MgCl 2  3, HEPES 5, pH 7.2). To apply a substance, the perfusion solution was exchanged for a substance solution with the same composition and additionally the desired substance concentration. To check the expression of the DNA, the holding potential (−60 mV) of the membrane was clamped in succession and stepped fashion onto 10 depolarizing and 10 hyperpolarizing potentials. The duration of the pulses was 100 ms. The voltage interval was 10 mV per step. Unresponsive oocytes were discarded. All the others were used for substance testing. The data were documented by means of a YT platter (YT platter, Model BD 111, Kipp &amp; Zonen Delft BV, AM Delft, Netherlands). When test substances were assayed in concentration series, these measurements were carried out on at least two different oocytes and at least five different concentrations. The substances have been assayed directly and without preincubation for their antagonism. The individual data were entered in Origin (evaluation software, Microcal Software, Inc., Northampton, Mass. 01060-4410 U.S.A. (Additive GmbH, Friedrichsdorf/Ts, Germany). Means and standard deviations were calculated using Origin. These measurements were carried out at least in duplicate.  
     [0086] References:  
     [0087] Arena J. P. et al. (1995), The mechanism of action of avermectins in  Caenorhabditis elegans:  correlation between activation of glutamate-sensitive chloride current, membrane binding, and biological activity, J. Parasitol. 81 (2), 286-294  
     [0088] Cleland T. A. (1996), Inhibitory glutamate receptor channels, Mol. Neurobiol. 13 (2), 97-136  
     [0089] Cully D. F. et al. (1994), Cloning of an avermectin-sensitive glutamate-gated chloride channel from  Caenorhabditis elegans,  Nature 371, 707-711  
     [0090] Cully D. F. et al. (1996), Identification of a  Drosophila melanogaster  glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin, J. Biol. Chem. 271 (33), 20187-20191  
     [0091] Delgado R. (1989), L-glutamate activates excitatory and inhibitory channels in Drosophila larval muscle, FEBS letters 243 (2), 337-342  
     [0092] Devereux et al. (1984), Nucleic Acids Research 12, 387  
     [0093] Dumont, J. N. (1972), Oogenesis in  Xenopus laevis  (Daudin). 1. Stages of oocyte development in laboratory maintained animals, J. Morphol. 136: 153-180  
     [0094] ffrench-Constant R. H. et al. (1991), Proc. Natl. Acad. Sci. U.S.A.88, 7209-7213  
     [0095] Harvey R. J. et al. (1994), Sequence of a Drosophila ligand-gated ion-channel polypeptide with an unusual amino-terminal extracellular domain, J. Neurochem. 62, 2480-2483  
     [0096] Hay et al. (1997), P element insertion-dependent gene activation in the Drosophila eye, Proceedings of The National Academy of Sciences of The United States of America 94 (10), 5195-5200  
     [0097] Henderson J. E. et al. (1993), Characterization of a putative gamma-aminobutyric acid (GABA) receptor beta subunit gene from  Drosophila melanogaster,  Biochem. Biophys. Res. Commun. 193, 474-482  
     [0098] Hosie A. M. et al. (1997), Molecular biology of insect neuronal GABA receptors, TINS 20, 578-583  
     [0099] Plasterk (1996), The Tcl/marinertransposon family, Transposable Elements/Current Topics in Microbiology and Immunology 204,125-143  
     [0100] Rudy et al., eds. (1992), Methods in Enzymology 207, Academic Press, Inc., San Diego, Calif.  
     [0101] Sambrook et al. (1989), Molecular Cloning, A Laboratory Manual, 2nd ed. Cold Spring Harbour Press  
     [0102] Sattelle D. B. (1990), GABA Receptors of Insects, Advances in Insect Physiology 22, 1-113  
     [0103] Satelle D. B. (1992), Receptors for L-glutamate and GABA in the nervous system of an insect (Periplaneta americana), Comp. Biochem. Physiol. C. 103 (3), 429-438  
     [0104] Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims.  
    
     
       
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             18  
           
           
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             1575  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1572)  
             
           
            1 

atg gag tgg tcg ctc atc ata tcg att ctg ctc aac tgc ctc tac gcc       48 
Met Glu Trp Ser Leu Ile Ile Ser Ile Leu Leu Asn Cys Leu Tyr Ala 
  1               5                  10                  15 

agc gcc tcc gcg ctc gac gag gat tgc ccc acc ttg gac gat ggg gac       96 
Ser Ala Ser Ala Leu Asp Glu Asp Cys Pro Thr Leu Asp Asp Gly Asp 
             20                  25                  30 

agt ttg tcg caa aca cag ctg ctg gat cgc tta acc cat ggc tgc cgc      144 
Ser Leu Ser Gln Thr Gln Leu Leu Asp Arg Leu Thr His Gly Cys Arg 
         35                  40                  45 

tac gat cgt ttg gaa cga ccc ata act tat tcg gaa act ggc cag cgg      192 
Tyr Asp Arg Leu Glu Arg Pro Ile Thr Tyr Ser Glu Thr Gly Gln Arg 
     50                  55                  60 

cta ccg gtg gac gtc tat atg cgc gcc tac atc tac ttc atg cag aac      240 
Leu Pro Val Asp Val Tyr Met Arg Ala Tyr Ile Tyr Phe Met Gln Asn 
 65                  70                  75                  80 

ctg gaa gca cac gat cta cag ttc aag atc tat gcg ctc ctc caa atg      288 
Leu Glu Ala His Asp Leu Gln Phe Lys Ile Tyr Ala Leu Leu Gln Met 
                 85                  90                  95 

cga tac ctc gat ccg cgt ctc aac ttt cgc aac gta agt ccc aag cgc      336 
Arg Tyr Leu Asp Pro Arg Leu Asn Phe Arg Asn Val Ser Pro Lys Arg 
            100                 105                 110 

agg cag ccg att ttg ggc gag gag cac ctg aga aac tcg ctc tgg atg      384 
Arg Gln Pro Ile Leu Gly Glu Glu His Leu Arg Asn Ser Leu Trp Met 
        115                 120                 125 

ccc cac ata ttt cta gcc aat gag cgc gac tcc agt att ttg ggt ctc      432 
Pro His Ile Phe Leu Ala Asn Glu Arg Asp Ser Ser Ile Leu Gly Leu 
    130                 135                 140 

acg gag aag gac atc ctc acc tcg ata tcg ccc gat ggc aca gtg atc      480 
Thr Glu Lys Asp Ile Leu Thr Ser Ile Ser Pro Asp Gly Thr Val Ile 
145                 150                 155                 160 

gtt tcg aat cgc atc aag gcg aca ctc tat tgc tgg ctc aac ctt aag      528 
Val Ser Asn Arg Ile Lys Ala Thr Leu Tyr Cys Trp Leu Asn Leu Lys 
                165                 170                 175 

aag ttc cca ttc gat gag cag cac tgc tcg acg gtg ctg gag agt tgg      576 
Lys Phe Pro Phe Asp Glu Gln His Cys Ser Thr Val Leu Glu Ser Trp 
            180                 185                 190 

atg tac aat acg tcg gaa ctg gtc ctc cac tgg gag cag aag cgt ccg      624 
Met Tyr Asn Thr Ser Glu Leu Val Leu His Trp Glu Gln Lys Arg Pro 
        195                 200                 205 

ata acc tac gat ggg gca ctg cat ctc acc gag ttt gtg ctg cag cgt      672 
Ile Thr Tyr Asp Gly Ala Leu His Leu Thr Glu Phe Val Leu Gln Arg 
    210                 215                 220 

tcc tgg tca aac gag acg gta atc aat gcc gat ttg agt gac ctg cgt      720 
Ser Trp Ser Asn Glu Thr Val Ile Asn Ala Asp Leu Ser Asp Leu Arg 
225                 230                 235                 240 

cat gga gcc ttt gcc ggc aac tac agc tcc ctc agc ttc acc gtt cac      768 
His Gly Ala Phe Ala Gly Asn Tyr Ser Ser Leu Ser Phe Thr Val His 
                245                 250                 255 

ctg acg cga gtg gtt ggc ttt tac ctg atg gac tac ttt cta ccc tcc      816 
Leu Thr Arg Val Val Gly Phe Tyr Leu Met Asp Tyr Phe Leu Pro Ser 
            260                 265                 270 

atg ctg att gtg gcc ata tcc tgg gta tcg ttc tgg ctg caa gca gat      864 
Met Leu Ile Val Ala Ile Ser Trp Val Ser Phe Trp Leu Gln Ala Asp 
        275                 280                 285 

cag gcg ccg ccg cgc atc acg ctg ggc acc agc acc ctg ctg aca ttc      912 
Gln Ala Pro Pro Arg Ile Thr Leu Gly Thr Ser Thr Leu Leu Thr Phe 
    290                 295                 300 

att acc ctg gcc tcg gca cag gga aag act ctg cca aag gtt agc tac      960 
Ile Thr Leu Ala Ser Ala Gln Gly Lys Thr Leu Pro Lys Val Ser Tyr 
305                 310                 315                 320 

atc aag gtg tca gag gtg tgg ttc ctg ggc tgc acc atc ttc ata ttt     1008 
Ile Lys Val Ser Glu Val Trp Phe Leu Gly Cys Thr Ile Phe Ile Phe 
                325                 330                 335 

ggc agc atg gtg gag ttc gcc ttt gtt aac acg att tgg cgt cgt aag     1056 
Gly Ser Met Val Glu Phe Ala Phe Val Asn Thr Ile Trp Arg Arg Lys 
            340                 345                 350 

aag agt gtg ccc gtc aag aaa ctg aac agc aaa cac atc ctg aag tca     1104 
Lys Ser Val Pro Val Lys Lys Leu Asn Ser Lys His Ile Leu Lys Ser 
        355                 360                 365 

act cta tcg ccg aat ctg ctc aga aga cgc agt cac gcc aga tcc aga     1152 
Thr Leu Ser Pro Asn Leu Leu Arg Arg Arg Ser His Ala Arg Ser Arg 
    370                 375                 380 

tcc ttt tcg ggc acg gct ctg cat aag aca gcg gat acc ggc tcg ctg     1200 
Ser Phe Ser Gly Thr Ala Leu His Lys Thr Ala Asp Thr Gly Ser Leu 
385                 390                 395                 400 

ggc ggt gcc ggt ttc aac aat tac cta acc gtc aat ttg ccc atc acc     1248 
Gly Gly Ala Gly Phe Asn Asn Tyr Leu Thr Val Asn Leu Pro Ile Thr 
                405                 410                 415 

acg att aag gag ggc caa gtt ctg gat cag cag agg acc agc cgc gtc     1296 
Thr Ile Lys Glu Gly Gln Val Leu Asp Gln Gln Arg Thr Ser Arg Val 
            420                 425                 430 

gtc cag aag atg gat gtt aac ttt gtg gag agt gcc ttt gga tcc atg     1344 
Val Gln Lys Met Asp Val Asn Phe Val Glu Ser Ala Phe Gly Ser Met 
        435                 440                 445 

ggc tct gcc cag tcc act gga gcg atc agt gct gcc agc agc agc caa     1392 
Gly Ser Ala Gln Ser Thr Gly Ala Ile Ser Ala Ala Ser Ser Ser Gln 
    450                 455                 460 

act ttg acc aac aat aac cga acg gag agc gcg ggg cac cag gag gag     1440 
Thr Leu Thr Asn Asn Asn Arg Thr Glu Ser Ala Gly His Gln Glu Glu 
465                 470                 475                 480 

atc gat ctg agt ggc tgg acc acg cta acg ccc cag gaa ata gcc atg     1488 
Ile Asp Leu Ser Gly Trp Thr Thr Leu Thr Pro Gln Glu Ile Ala Met 
                485                 490                 495 

tgg att gat agt cga gcc aga ttc gtt ttt ccg ctc tcc ttt ctc gtc     1536 
Trp Ile Asp Ser Arg Ala Arg Phe Val Phe Pro Leu Ser Phe Leu Val 
            500                 505                 510 

ttt aat ctg ttt ttc tgg aca ttt gtc tac tgt att taa                 1575 
Phe Asn Leu Phe Phe Trp Thr Phe Val Tyr Cys Ile 
        515                 520 

 
           
             2  
             524  
             PRT  
             Drosophila melanogaster  
           
            2 

Met Glu Trp Ser Leu Ile Ile Ser Ile Leu Leu Asn Cys Leu Tyr Ala 
  1               5                  10                  15 

Ser Ala Ser Ala Leu Asp Glu Asp Cys Pro Thr Leu Asp Asp Gly Asp 
             20                  25                  30 

Ser Leu Ser Gln Thr Gln Leu Leu Asp Arg Leu Thr His Gly Cys Arg 
         35                  40                  45 

Tyr Asp Arg Leu Glu Arg Pro Ile Thr Tyr Ser Glu Thr Gly Gln Arg 
     50                  55                  60 

Leu Pro Val Asp Val Tyr Met Arg Ala Tyr Ile Tyr Phe Met Gln Asn 
 65                  70                  75                  80 

Leu Glu Ala His Asp Leu Gln Phe Lys Ile Tyr Ala Leu Leu Gln Met 
                 85                  90                  95 

Arg Tyr Leu Asp Pro Arg Leu Asn Phe Arg Asn Val Ser Pro Lys Arg 
            100                 105                 110 

Arg Gln Pro Ile Leu Gly Glu Glu His Leu Arg Asn Ser Leu Trp Met 
        115                 120                 125 

Pro His Ile Phe Leu Ala Asn Glu Arg Asp Ser Ser Ile Leu Gly Leu 
    130                 135                 140 

Thr Glu Lys Asp Ile Leu Thr Ser Ile Ser Pro Asp Gly Thr Val Ile 
145                 150                 155                 160 

Val Ser Asn Arg Ile Lys Ala Thr Leu Tyr Cys Trp Leu Asn Leu Lys 
                165                 170                 175 

Lys Phe Pro Phe Asp Glu Gln His Cys Ser Thr Val Leu Glu Ser Trp 
            180                 185                 190 

Met Tyr Asn Thr Ser Glu Leu Val Leu His Trp Glu Gln Lys Arg Pro 
        195                 200                 205 

Ile Thr Tyr Asp Gly Ala Leu His Leu Thr Glu Phe Val Leu Gln Arg 
    210                 215                 220 

Ser Trp Ser Asn Glu Thr Val Ile Asn Ala Asp Leu Ser Asp Leu Arg 
225                 230                 235                 240 

His Gly Ala Phe Ala Gly Asn Tyr Ser Ser Leu Ser Phe Thr Val His 
                245                 250                 255 

Leu Thr Arg Val Val Gly Phe Tyr Leu Met Asp Tyr Phe Leu Pro Ser 
            260                 265                 270 

Met Leu Ile Val Ala Ile Ser Trp Val Ser Phe Trp Leu Gln Ala Asp 
        275                 280                 285 

Gln Ala Pro Pro Arg Ile Thr Leu Gly Thr Ser Thr Leu Leu Thr Phe 
    290                 295                 300 

Ile Thr Leu Ala Ser Ala Gln Gly Lys Thr Leu Pro Lys Val Ser Tyr 
305                 310                 315                 320 

Ile Lys Val Ser Glu Val Trp Phe Leu Gly Cys Thr Ile Phe Ile Phe 
                325                 330                 335 

Gly Ser Met Val Glu Phe Ala Phe Val Asn Thr Ile Trp Arg Arg Lys 
            340                 345                 350 

Lys Ser Val Pro Val Lys Lys Leu Asn Ser Lys His Ile Leu Lys Ser 
        355                 360                 365 

Thr Leu Ser Pro Asn Leu Leu Arg Arg Arg Ser His Ala Arg Ser Arg 
    370                 375                 380 

Ser Phe Ser Gly Thr Ala Leu His Lys Thr Ala Asp Thr Gly Ser Leu 
385                 390                 395                 400 

Gly Gly Ala Gly Phe Asn Asn Tyr Leu Thr Val Asn Leu Pro Ile Thr 
                405                 410                 415 

Thr Ile Lys Glu Gly Gln Val Leu Asp Gln Gln Arg Thr Ser Arg Val 
            420                 425                 430 

Val Gln Lys Met Asp Val Asn Phe Val Glu Ser Ala Phe Gly Ser Met 
        435                 440                 445 

Gly Ser Ala Gln Ser Thr Gly Ala Ile Ser Ala Ala Ser Ser Ser Gln 
    450                 455                 460 

Thr Leu Thr Asn Asn Asn Arg Thr Glu Ser Ala Gly His Gln Glu Glu 
465                 470                 475                 480 

Ile Asp Leu Ser Gly Trp Thr Thr Leu Thr Pro Gln Glu Ile Ala Met 
                485                 490                 495 

Trp Ile Asp Ser Arg Ala Arg Phe Val Phe Pro Leu Ser Phe Leu Val 
            500                 505                 510 

Phe Asn Leu Phe Phe Trp Thr Phe Val Tyr Cys Ile 
        515                 520 

 
           
             3  
             1269  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1266)  
             
           
            3 

atg caa agc cca act agc aaa ttg gta gaa ttc agg tgc ctg att gcg       48 
Met Gln Ser Pro Thr Ser Lys Leu Val Glu Phe Arg Cys Leu Ile Ala 
  1               5                  10                  15 

ttg gca ata tat ttg cac gcg ctg gag caa tcg atc cag cac tgc cat       96 
Leu Ala Ile Tyr Leu His Ala Leu Glu Gln Ser Ile Gln His Cys His 
             20                  25                  30 

tgt gtt cat ggt tac aga aat aac acg gag agc gcc gag ctg gtc tcc      144 
Cys Val His Gly Tyr Arg Asn Asn Thr Glu Ser Ala Glu Leu Val Ser 
         35                  40                  45 

cac tac gag tcg agt ctt tcg ctc ccg gac att ttg ccc att ccc tca      192 
His Tyr Glu Ser Ser Leu Ser Leu Pro Asp Ile Leu Pro Ile Pro Ser 
     50                  55                  60 

aag acg tac gac aag aac cgg gct ccc aag ctc ctc ggc cag ccc aca      240 
Lys Thr Tyr Asp Lys Asn Arg Ala Pro Lys Leu Leu Gly Gln Pro Thr 
 65                  70                  75                  80 

gta gtc tac ttc cat gtc acg gtc ctc tcc ctg gac tcc att aac gag      288 
Val Val Tyr Phe His Val Thr Val Leu Ser Leu Asp Ser Ile Asn Glu 
                 85                  90                  95 

gag tct atg acc tat gtg acg gac atc ttc ctt gca caa agc tgg cgt      336 
Glu Ser Met Thr Tyr Val Thr Asp Ile Phe Leu Ala Gln Ser Trp Arg 
            100                 105                 110 

gat cct cgc ctg cgg ttg cct gag aac atg agt gag cag tat cgc ata      384 
Asp Pro Arg Leu Arg Leu Pro Glu Asn Met Ser Glu Gln Tyr Arg Ile 
        115                 120                 125 

ttg gat gtc gac tgg ttg cac agc att tgg cgg ccc gat tgc ttc ttt      432 
Leu Asp Val Asp Trp Leu His Ser Ile Trp Arg Pro Asp Cys Phe Phe 
    130                 135                 140 

aag aac gcc aaa aag gtc acc ttc cat gag atg agc att ccc aat cac      480 
Lys Asn Ala Lys Lys Val Thr Phe His Glu Met Ser Ile Pro Asn His 
145                 150                 155                 160 

tat ctc tgg ctg tac cac gac aaa acg ctg ctc tat atg tcc aaa ctc      528 
Tyr Leu Trp Leu Tyr His Asp Lys Thr Leu Leu Tyr Met Ser Lys Leu 
                165                 170                 175 

acg ttg gtc ctg tcg tgc gcc atg aag ttt gag tcc tat ccg cat gac      576 
Thr Leu Val Leu Ser Cys Ala Met Lys Phe Glu Ser Tyr Pro His Asp 
            180                 185                 190 

acg caa atc tgc tcc atg atg atc gag agt tta tcc cat acg gtg gaa      624 
Thr Gln Ile Cys Ser Met Met Ile Glu Ser Leu Ser His Thr Val Glu 
        195                 200                 205 

gat ttg gtt ttc att tgg aac atg acc gac cca ctt gtg gtt aac acg      672 
Asp Leu Val Phe Ile Trp Asn Met Thr Asp Pro Leu Val Val Asn Thr 
    210                 215                 220 

gag att gag ttg ccg cag cta gac ata tca aat aac tac aca acc gac      720 
Glu Ile Glu Leu Pro Gln Leu Asp Ile Ser Asn Asn Tyr Thr Thr Asp 
225                 230                 235                 240 

tgt act ata gag tac tca aca ggt aac ttc acc tgc ctg gcc att gtg      768 
Cys Thr Ile Glu Tyr Ser Thr Gly Asn Phe Thr Cys Leu Ala Ile Val 
                245                 250                 255 

ttc aac ctg cgc cga cgc ctg ggt tac cat ttg ttc cac acc tac atc      816 
Phe Asn Leu Arg Arg Arg Leu Gly Tyr His Leu Phe His Thr Tyr Ile 
            260                 265                 270 

ccc tcg gct ctg att gtg gtc atg tct tgg ata tcg ttt tgg ata aaa      864 
Pro Ser Ala Leu Ile Val Val Met Ser Trp Ile Ser Phe Trp Ile Lys 
        275                 280                 285 

cca gaa gcg ata ccc gcc cgt gta act ctg gga gtg acc tca ctg cta      912 
Pro Glu Ala Ile Pro Ala Arg Val Thr Leu Gly Val Thr Ser Leu Leu 
    290                 295                 300 

acc ctg gcc acc cag aat acc cag tcg caa caa tcg ctg ccg ccg gtt      960 
Thr Leu Ala Thr Gln Asn Thr Gln Ser Gln Gln Ser Leu Pro Pro Val 
305                 310                 315                 320 

tcg tat gtc aag gct ata gac gtc tgg atg tcg tcc tgt tcg gtg ttt     1008 
Ser Tyr Val Lys Ala Ile Asp Val Trp Met Ser Ser Cys Ser Val Phe 
                325                 330                 335 

gta ttc ctt tct ctg atg gaa ttt gca gtg gtc aac aat ttt atg gga     1056 
Val Phe Leu Ser Leu Met Glu Phe Ala Val Val Asn Asn Phe Met Gly 
            340                 345                 350 

ccg gtg gcc aca aag gca atg aag ggg tat tcg gac gag aac atc agt     1104 
Pro Val Ala Thr Lys Ala Met Lys Gly Tyr Ser Asp Glu Asn Ile Ser 
        355                 360                 365 

gat ctg gac gac cta aag cat cat cgg gaa tcg att att gag ccc cag     1152 
Asp Leu Asp Asp Leu Lys His His Arg Glu Ser Ile Ile Glu Pro Gln 
    370                 375                 380 

ttc gac cct ttt tgc cat ggc cct gcc cca gcc ctt tat ata gac aaa     1200 
Phe Asp Pro Phe Cys His Gly Pro Ala Pro Ala Leu Tyr Ile Asp Lys 
385                 390                 395                 400 

ttc tcg cgc ttt ttc ttc ccg ttt tcg ttc ttt ata ctc aat att gtc     1248 
Phe Ser Arg Phe Phe Phe Pro Phe Ser Phe Phe Ile Leu Asn Ile Val 
                405                 410                 415 

tat tgg aca acg ttc cta tga                                         1269 
Tyr Trp Thr Thr Phe Leu 
            420 

 
           
             4  
             422  
             PRT  
             Drosophila melanogaster  
           
            4 

Met Gln Ser Pro Thr Ser Lys Leu Val Glu Phe Arg Cys Leu Ile Ala 
  1               5                  10                  15 

Leu Ala Ile Tyr Leu His Ala Leu Glu Gln Ser Ile Gln His Cys His 
             20                  25                  30 

Cys Val His Gly Tyr Arg Asn Asn Thr Glu Ser Ala Glu Leu Val Ser 
         35                  40                  45 

His Tyr Glu Ser Ser Leu Ser Leu Pro Asp Ile Leu Pro Ile Pro Ser 
     50                  55                  60 

Lys Thr Tyr Asp Lys Asn Arg Ala Pro Lys Leu Leu Gly Gln Pro Thr 
 65                  70                  75                  80 

Val Val Tyr Phe His Val Thr Val Leu Ser Leu Asp Ser Ile Asn Glu 
                 85                  90                  95 

Glu Ser Met Thr Tyr Val Thr Asp Ile Phe Leu Ala Gln Ser Trp Arg 
            100                 105                 110 

Asp Pro Arg Leu Arg Leu Pro Glu Asn Met Ser Glu Gln Tyr Arg Ile 
        115                 120                 125 

Leu Asp Val Asp Trp Leu His Ser Ile Trp Arg Pro Asp Cys Phe Phe 
    130                 135                 140 

Lys Asn Ala Lys Lys Val Thr Phe His Glu Met Ser Ile Pro Asn His 
145                 150                 155                 160 

Tyr Leu Trp Leu Tyr His Asp Lys Thr Leu Leu Tyr Met Ser Lys Leu 
                165                 170                 175 

Thr Leu Val Leu Ser Cys Ala Met Lys Phe Glu Ser Tyr Pro His Asp 
            180                 185                 190 

Thr Gln Ile Cys Ser Met Met Ile Glu Ser Leu Ser His Thr Val Glu 
        195                 200                 205 

Asp Leu Val Phe Ile Trp Asn Met Thr Asp Pro Leu Val Val Asn Thr 
    210                 215                 220 

Glu Ile Glu Leu Pro Gln Leu Asp Ile Ser Asn Asn Tyr Thr Thr Asp 
225                 230                 235                 240 

Cys Thr Ile Glu Tyr Ser Thr Gly Asn Phe Thr Cys Leu Ala Ile Val 
                245                 250                 255 

Phe Asn Leu Arg Arg Arg Leu Gly Tyr His Leu Phe His Thr Tyr Ile 
            260                 265                 270 

Pro Ser Ala Leu Ile Val Val Met Ser Trp Ile Ser Phe Trp Ile Lys 
        275                 280                 285 

Pro Glu Ala Ile Pro Ala Arg Val Thr Leu Gly Val Thr Ser Leu Leu 
    290                 295                 300 

Thr Leu Ala Thr Gln Asn Thr Gln Ser Gln Gln Ser Leu Pro Pro Val 
305                 310                 315                 320 

Ser Tyr Val Lys Ala Ile Asp Val Trp Met Ser Ser Cys Ser Val Phe 
                325                 330                 335 

Val Phe Leu Ser Leu Met Glu Phe Ala Val Val Asn Asn Phe Met Gly 
            340                 345                 350 

Pro Val Ala Thr Lys Ala Met Lys Gly Tyr Ser Asp Glu Asn Ile Ser 
        355                 360                 365 

Asp Leu Asp Asp Leu Lys His His Arg Glu Ser Ile Ile Glu Pro Gln 
    370                 375                 380 

Phe Asp Pro Phe Cys His Gly Pro Ala Pro Ala Leu Tyr Ile Asp Lys 
385                 390                 395                 400 

Phe Ser Arg Phe Phe Phe Pro Phe Ser Phe Phe Ile Leu Asn Ile Val 
                405                 410                 415 

Tyr Trp Thr Thr Phe Leu 
            420 

 
           
             5  
             1192  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1191)  
             
           
            5 

atg caa agc cca act agc aaa ttg gta gaa ttc agg tgc ctg att gcg       48 
Met Gln Ser Pro Thr Ser Lys Leu Val Glu Phe Arg Cys Leu Ile Ala 
  1               5                  10                  15 

ttg gca ata tat ttg cac gcg ctg gag caa tcg atc cag cac tgc cat       96 
Leu Ala Ile Tyr Leu His Ala Leu Glu Gln Ser Ile Gln His Cys His 
             20                  25                  30 

tgt gtt cat ggt tac aga aat aac acg gag agc gcc gag ctg gtc tcc      144 
Cys Val His Gly Tyr Arg Asn Asn Thr Glu Ser Ala Glu Leu Val Ser 
         35                  40                  45 

cac tac gag tcg agt ctt tcg ctc ccg gac att ttg ccc att ccc tca      192 
His Tyr Glu Ser Ser Leu Ser Leu Pro Asp Ile Leu Pro Ile Pro Ser 
     50                  55                  60 

aag acg tac gac aag aac cgg gct ccc aag ctc ctc ggc cag ccc aca      240 
Lys Thr Tyr Asp Lys Asn Arg Ala Pro Lys Leu Leu Gly Gln Pro Thr 
 65                  70                  75                  80 

gta gtc tac ttc cat gtc acg gtc ctc tcc ctg gac tcc att aac gag      288 
Val Val Tyr Phe His Val Thr Val Leu Ser Leu Asp Ser Ile Asn Glu 
                 85                  90                  95 

gag tct atg acc tat gtg acg gac atc ttc ctt gca caa agc tgg cgt      336 
Glu Ser Met Thr Tyr Val Thr Asp Ile Phe Leu Ala Gln Ser Trp Arg 
            100                 105                 110 

gat cct cgc ctg cgg ttg cct gag aac atg agt gag cag tat cgc ata      384 
Asp Pro Arg Leu Arg Leu Pro Glu Asn Met Ser Glu Gln Tyr Arg Ile 
        115                 120                 125 

ttg gat gtc gac tgg ttg cac agc att tgg cgg ccc gat tgc ttc ttt      432 
Leu Asp Val Asp Trp Leu His Ser Ile Trp Arg Pro Asp Cys Phe Phe 
    130                 135                 140 

aag aac gcc aaa aag gtc acc ttc cat gag atg agc att ccc aat cac      480 
Lys Asn Ala Lys Lys Val Thr Phe His Glu Met Ser Ile Pro Asn His 
145                 150                 155                 160 

tat ctc tgg ctg tac cac gac aaa acg ctg ctc tat atg tcc aaa ctc      528 
Tyr Leu Trp Leu Tyr His Asp Lys Thr Leu Leu Tyr Met Ser Lys Leu 
                165                 170                 175 

acg ttg gtc ctg tcg tgc gcc atg aag ttt gag tcc tat ccg cat gac      576 
Thr Leu Val Leu Ser Cys Ala Met Lys Phe Glu Ser Tyr Pro His Asp 
            180                 185                 190 

acg caa atc tgc tcc atg atg atc gag agt tta tcc cat acg gtg gaa      624 
Thr Gln Ile Cys Ser Met Met Ile Glu Ser Leu Ser His Thr Val Glu 
        195                 200                 205 

gat ttg gtt ttc att tgg aac atg acc gac cca ctt gtg gtt aac acg      672 
Asp Leu Val Phe Ile Trp Asn Met Thr Asp Pro Leu Val Val Asn Thr 
    210                 215                 220 

gag att gag ttg ccg cag cta gac ata tca aat aac tac aca acc gac      720 
Glu Ile Glu Leu Pro Gln Leu Asp Ile Ser Asn Asn Tyr Thr Thr Asp 
225                 230                 235                 240 

tgt act ata gag tac tca aca ggt aac ttc acc tgc ctg gcc att gtg      768 
Cys Thr Ile Glu Tyr Ser Thr Gly Asn Phe Thr Cys Leu Ala Ile Val 
                245                 250                 255 

ttc aac ctg cgc cga cgc ctg ggt tac cat ttg ttc cac acc tac atc      816 
Phe Asn Leu Arg Arg Arg Leu Gly Tyr His Leu Phe His Thr Tyr Ile 
            260                 265                 270 

ccc tcg gct ctg att gtg gtc atg tct tgg ata tcg ttt tgg ata aaa      864 
Pro Ser Ala Leu Ile Val Val Met Ser Trp Ile Ser Phe Trp Ile Lys 
        275                 280                 285 

cca gaa gcg ata ccc gcc cgt gta act ctg gga gtg acc tca ctg cta      912 
Pro Glu Ala Ile Pro Ala Arg Val Thr Leu Gly Val Thr Ser Leu Leu 
    290                 295                 300 

acc ctg gcc acc cag aat acc cag tcg caa caa tcg ctg ccg ccg gtt      960 
Thr Leu Ala Thr Gln Asn Thr Gln Ser Gln Gln Ser Leu Pro Pro Val 
305                 310                 315                 320 

tcg tat gtc aag gct ata gac gtc tgg atg tcg tcc tgt tcg gtg ttt     1008 
Ser Tyr Val Lys Ala Ile Asp Val Trp Met Ser Ser Cys Ser Val Phe 
                325                 330                 335 

gta ttc ctt tct ctg atg gaa ttt gca gtg gtc aac aat ttt atg gga     1056 
Val Phe Leu Ser Leu Met Glu Phe Ala Val Val Asn Asn Phe Met Gly 
            340                 345                 350 

ccg gtg gcc aca aag gca atg aag ggg tat tcg gac gag aac atc agt     1104 
Pro Val Ala Thr Lys Ala Met Lys Gly Tyr Ser Asp Glu Asn Ile Ser 
        355                 360                 365 

gat ctg gac gac cta aag cat cat cgg gaa tcg att att gag ccc cag     1152 
Asp Leu Asp Asp Leu Lys His His Arg Glu Ser Ile Ile Glu Pro Gln 
    370                 375                 380 

tac gac act ttc tgc cat ggc cat gcc acg cca ttt ata t               1192 
Tyr Asp Thr Phe Cys His Gly His Ala Thr Pro Phe Ile 
385                 390                 395 

 
           
             6  
             397  
             PRT  
             Drosophila melanogaster  
           
            6 

Met Gln Ser Pro Thr Ser Lys Leu Val Glu Phe Arg Cys Leu Ile Ala 
  1               5                  10                  15 

Leu Ala Ile Tyr Leu His Ala Leu Glu Gln Ser Ile Gln His Cys His 
             20                  25                  30 

Cys Val His Gly Tyr Arg Asn Asn Thr Glu Ser Ala Glu Leu Val Ser 
         35                  40                  45 

His Tyr Glu Ser Ser Leu Ser Leu Pro Asp Ile Leu Pro Ile Pro Ser 
     50                  55                  60 

Lys Thr Tyr Asp Lys Asn Arg Ala Pro Lys Leu Leu Gly Gln Pro Thr 
 65                  70                  75                  80 

Val Val Tyr Phe His Val Thr Val Leu Ser Leu Asp Ser Ile Asn Glu 
                 85                  90                  95 

Glu Ser Met Thr Tyr Val Thr Asp Ile Phe Leu Ala Gln Ser Trp Arg 
            100                 105                 110 

Asp Pro Arg Leu Arg Leu Pro Glu Asn Met Ser Glu Gln Tyr Arg Ile 
        115                 120                 125 

Leu Asp Val Asp Trp Leu His Ser Ile Trp Arg Pro Asp Cys Phe Phe 
    130                 135                 140 

Lys Asn Ala Lys Lys Val Thr Phe His Glu Met Ser Ile Pro Asn His 
145                 150                 155                 160 

Tyr Leu Trp Leu Tyr His Asp Lys Thr Leu Leu Tyr Met Ser Lys Leu 
                165                 170                 175 

Thr Leu Val Leu Ser Cys Ala Met Lys Phe Glu Ser Tyr Pro His Asp 
            180                 185                 190 

Thr Gln Ile Cys Ser Met Met Ile Glu Ser Leu Ser His Thr Val Glu 
        195                 200                 205 

Asp Leu Val Phe Ile Trp Asn Met Thr Asp Pro Leu Val Val Asn Thr 
    210                 215                 220 

Glu Ile Glu Leu Pro Gln Leu Asp Ile Ser Asn Asn Tyr Thr Thr Asp 
225                 230                 235                 240 

Cys Thr Ile Glu Tyr Ser Thr Gly Asn Phe Thr Cys Leu Ala Ile Val 
                245                 250                 255 

Phe Asn Leu Arg Arg Arg Leu Gly Tyr His Leu Phe His Thr Tyr Ile 
            260                 265                 270 

Pro Ser Ala Leu Ile Val Val Met Ser Trp Ile Ser Phe Trp Ile Lys 
        275                 280                 285 

Pro Glu Ala Ile Pro Ala Arg Val Thr Leu Gly Val Thr Ser Leu Leu 
    290                 295                 300 

Thr Leu Ala Thr Gln Asn Thr Gln Ser Gln Gln Ser Leu Pro Pro Val 
305                 310                 315                 320 

Ser Tyr Val Lys Ala Ile Asp Val Trp Met Ser Ser Cys Ser Val Phe 
                325                 330                 335 

Val Phe Leu Ser Leu Met Glu Phe Ala Val Val Asn Asn Phe Met Gly 
            340                 345                 350 

Pro Val Ala Thr Lys Ala Met Lys Gly Tyr Ser Asp Glu Asn Ile Ser 
        355                 360                 365 

Asp Leu Asp Asp Leu Lys His His Arg Glu Ser Ile Ile Glu Pro Gln 
    370                 375                 380 

Tyr Asp Thr Phe Cys His Gly His Ala Thr Pro Phe Ile 
385                 390                 395 

 
           
             7  
             1272  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1269)  
             
           
            7 

atg gag tcc gag tgc gtt tgc cca gtt tca tca gat tta cgc cac agg       48 
Met Glu Ser Glu Cys Val Cys Pro Val Ser Ser Asp Leu Arg His Arg 
  1               5                  10                  15 

gct gtt ctg ttc cac ata tgc aga aat aac acg gag agc gcc gag ctg       96 
Ala Val Leu Phe His Ile Cys Arg Asn Asn Thr Glu Ser Ala Glu Leu 
             20                  25                  30 

gtc tcc cac tac gag tcg agt ctt tcg ctc ccg gac att ttg ccc att      144 
Val Ser His Tyr Glu Ser Ser Leu Ser Leu Pro Asp Ile Leu Pro Ile 
         35                  40                  45 

ccc tca aag acg tac gac aag aac cgg gct ccc aag ctc ctc ggc cag      192 
Pro Ser Lys Thr Tyr Asp Lys Asn Arg Ala Pro Lys Leu Leu Gly Gln 
     50                  55                  60 

ccc aca gta gtc tac ttc cat gtc acg gtc ctc tcc ctg gac tcc att      240 
Pro Thr Val Val Tyr Phe His Val Thr Val Leu Ser Leu Asp Ser Ile 
 65                  70                  75                  80 

aac gag gag tct atg acc tat gtg acg gac atc ttc ctt gca caa agc      288 
Asn Glu Glu Ser Met Thr Tyr Val Thr Asp Ile Phe Leu Ala Gln Ser 
                 85                  90                  95 

tgg cgt gat cct cgc ctg cgg ttg cct gag aac atg agt gag cag tat      336 
Trp Arg Asp Pro Arg Leu Arg Leu Pro Glu Asn Met Ser Glu Gln Tyr 
            100                 105                 110 

cgc ata ttg gat gtc gac tgg ttg cac agc att tgg cgg ccc gat tgc      384 
Arg Ile Leu Asp Val Asp Trp Leu His Ser Ile Trp Arg Pro Asp Cys 
        115                 120                 125 

ttc ttt aag aac gcc aaa aag gtc acc ttc cat gag atg agc att ccc      432 
Phe Phe Lys Asn Ala Lys Lys Val Thr Phe His Glu Met Ser Ile Pro 
    130                 135                 140 

aat cac tat ctc tgg ctg tac cac gac aaa acg ctg ctc tat atg tcc      480 
Asn His Tyr Leu Trp Leu Tyr His Asp Lys Thr Leu Leu Tyr Met Ser 
145                 150                 155                 160 

aaa ctc acg ttg gtc ctg tcg tgc gcc atg aag ttt gag tcc tat ccg      528 
Lys Leu Thr Leu Val Leu Ser Cys Ala Met Lys Phe Glu Ser Tyr Pro 
                165                 170                 175 

cat gac acg caa atc tgc tcc atg atg atc gag agt tta tcc cat acg      576 
His Asp Thr Gln Ile Cys Ser Met Met Ile Glu Ser Leu Ser His Thr 
            180                 185                 190 

gtg gaa gat ttg gtt ttc att tgg aac atg acc gac cca ctt gtg gtt      624 
Val Glu Asp Leu Val Phe Ile Trp Asn Met Thr Asp Pro Leu Val Val 
        195                 200                 205 

aac acg gag att gag ttg ccg cag cta gac ata tca aat aac tac aca      672 
Asn Thr Glu Ile Glu Leu Pro Gln Leu Asp Ile Ser Asn Asn Tyr Thr 
    210                 215                 220 

acc gac tgt act ata gag tac tca aca ggt aac ttc acc tgc ctg gcc      720 
Thr Asp Cys Thr Ile Glu Tyr Ser Thr Gly Asn Phe Thr Cys Leu Ala 
225                 230                 235                 240 

att gtg ttc aac ctg cgc cga cgc ctg ggt tac cat ttg ttc cac acc      768 
Ile Val Phe Asn Leu Arg Arg Arg Leu Gly Tyr His Leu Phe His Thr 
                245                 250                 255 

tac atc ccc tcg gct ctg att gtg gtc atg tct tgg ata tcg ttt tgg      816 
Tyr Ile Pro Ser Ala Leu Ile Val Val Met Ser Trp Ile Ser Phe Trp 
            260                 265                 270 

ata aaa cca gaa gcg ata ccc gcc cgt gta act ctg gga gtg acc tca      864 
Ile Lys Pro Glu Ala Ile Pro Ala Arg Val Thr Leu Gly Val Thr Ser 
        275                 280                 285 

ctg cta acc ctg gcc acc cag aat acc cag tcg caa caa tcg ctg ccg      912 
Leu Leu Thr Leu Ala Thr Gln Asn Thr Gln Ser Gln Gln Ser Leu Pro 
    290                 295                 300 

ccg gtt tcg tat gtc aag gct ata gac gtc tgg atg tcg tcc tgt tcg      960 
Pro Val Ser Tyr Val Lys Ala Ile Asp Val Trp Met Ser Ser Cys Ser 
305                 310                 315                 320 

gtg ttt gta ttc ctt tct ctg atg gaa ttt gca gtg gtc aac aat ttt     1008 
Val Phe Val Phe Leu Ser Leu Met Glu Phe Ala Val Val Asn Asn Phe 
                325                 330                 335 

atg gga ccg gtg gcc aca aag gca atg aag ggg tat tcg gac gag aac     1056 
Met Gly Pro Val Ala Thr Lys Ala Met Lys Gly Tyr Ser Asp Glu Asn 
            340                 345                 350 

atc agt gat ctg gac gac cta aag gtt gtg cgg cag tta cag att gga     1104 
Ile Ser Asp Leu Asp Asp Leu Lys Val Val Arg Gln Leu Gln Ile Gly 
        355                 360                 365 

ctt cag cca gtt ctg aaa aag aag tta agc aat tac ttc aaa gtt cct     1152 
Leu Gln Pro Val Leu Lys Lys Lys Leu Ser Asn Tyr Phe Lys Val Pro 
    370                 375                 380 

aaa gcc ata ata aat gta ttt acc aat gat gcc ctt cgg agc ggt atc     1200 
Lys Ala Ile Ile Asn Val Phe Thr Asn Asp Ala Leu Arg Ser Gly Ile 
385                 390                 395                 400 

ttc gga ggt gtc ata gta acg aag ttg atg ctt aat aga gtc caa cga     1248 
Phe Gly Gly Val Ile Val Thr Lys Leu Met Leu Asn Arg Val Gln Arg 
                405                 410                 415 

acc atc gct gtt tcc agc cct tga                                     1272 
Thr Ile Ala Val Ser Ser Pro 
            420 

 
           
             8  
             423  
             PRT  
             Drosophila melanogaster  
           
            8 

Met Glu Ser Glu Cys Val Cys Pro Val Ser Ser Asp Leu Arg His Arg 
  1               5                  10                  15 

Ala Val Leu Phe His Ile Cys Arg Asn Asn Thr Glu Ser Ala Glu Leu 
             20                  25                  30 

Val Ser His Tyr Glu Ser Ser Leu Ser Leu Pro Asp Ile Leu Pro Ile 
         35                  40                  45 

Pro Ser Lys Thr Tyr Asp Lys Asn Arg Ala Pro Lys Leu Leu Gly Gln 
     50                  55                  60 

Pro Thr Val Val Tyr Phe His Val Thr Val Leu Ser Leu Asp Ser Ile 
 65                  70                  75                  80 

Asn Glu Glu Ser Met Thr Tyr Val Thr Asp Ile Phe Leu Ala Gln Ser 
                 85                  90                  95 

Trp Arg Asp Pro Arg Leu Arg Leu Pro Glu Asn Met Ser Glu Gln Tyr 
            100                 105                 110 

Arg Ile Leu Asp Val Asp Trp Leu His Ser Ile Trp Arg Pro Asp Cys 
        115                 120                 125 

Phe Phe Lys Asn Ala Lys Lys Val Thr Phe His Glu Met Ser Ile Pro 
    130                 135                 140 

Asn His Tyr Leu Trp Leu Tyr His Asp Lys Thr Leu Leu Tyr Met Ser 
145                 150                 155                 160 

Lys Leu Thr Leu Val Leu Ser Cys Ala Met Lys Phe Glu Ser Tyr Pro 
                165                 170                 175 

His Asp Thr Gln Ile Cys Ser Met Met Ile Glu Ser Leu Ser His Thr 
            180                 185                 190 

Val Glu Asp Leu Val Phe Ile Trp Asn Met Thr Asp Pro Leu Val Val 
        195                 200                 205 

Asn Thr Glu Ile Glu Leu Pro Gln Leu Asp Ile Ser Asn Asn Tyr Thr 
    210                 215                 220 

Thr Asp Cys Thr Ile Glu Tyr Ser Thr Gly Asn Phe Thr Cys Leu Ala 
225                 230                 235                 240 

Ile Val Phe Asn Leu Arg Arg Arg Leu Gly Tyr His Leu Phe His Thr 
                245                 250                 255 

Tyr Ile Pro Ser Ala Leu Ile Val Val Met Ser Trp Ile Ser Phe Trp 
            260                 265                 270 

Ile Lys Pro Glu Ala Ile Pro Ala Arg Val Thr Leu Gly Val Thr Ser 
        275                 280                 285 

Leu Leu Thr Leu Ala Thr Gln Asn Thr Gln Ser Gln Gln Ser Leu Pro 
    290                 295                 300 

Pro Val Ser Tyr Val Lys Ala Ile Asp Val Trp Met Ser Ser Cys Ser 
305                 310                 315                 320 

Val Phe Val Phe Leu Ser Leu Met Glu Phe Ala Val Val Asn Asn Phe 
                325                 330                 335 

Met Gly Pro Val Ala Thr Lys Ala Met Lys Gly Tyr Ser Asp Glu Asn 
            340                 345                 350 

Ile Ser Asp Leu Asp Asp Leu Lys Val Val Arg Gln Leu Gln Ile Gly 
        355                 360                 365 

Leu Gln Pro Val Leu Lys Lys Lys Leu Ser Asn Tyr Phe Lys Val Pro 
    370                 375                 380 

Lys Ala Ile Ile Asn Val Phe Thr Asn Asp Ala Leu Arg Ser Gly Ile 
385                 390                 395                 400 

Phe Gly Gly Val Ile Val Thr Lys Leu Met Leu Asn Arg Val Gln Arg 
                405                 410                 415 

Thr Ile Ala Val Ser Ser Pro 
            420 

 
           
             9  
             1608  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1605)  
             
           
            9 

atg gtg ttc caa ata ata atc ctg gtg atc tgc acc atc tgc atg aag       48 
Met Val Phe Gln Ile Ile Ile Leu Val Ile Cys Thr Ile Cys Met Lys 
  1               5                  10                  15 

cac tac gcc aaa ggg gag ttt caa caa agt ctg gcc ata acc gac atc       96 
His Tyr Ala Lys Gly Glu Phe Gln Gln Ser Leu Ala Ile Thr Asp Ile 
             20                  25                  30 

ctg ccc gag gac atc aag cgt tac gac aag atg aga ccg ccg aag aaa      144 
Leu Pro Glu Asp Ile Lys Arg Tyr Asp Lys Met Arg Pro Pro Lys Lys 
         35                  40                  45 

gag ggt cag ccg acg ata gtc tac ttc cat gtg acg gtg atg ggt ctg      192 
Glu Gly Gln Pro Thr Ile Val Tyr Phe His Val Thr Val Met Gly Leu 
     50                  55                  60 

gac tcc att gat gag aac tcg atg act tat gtg gcg gat gtg ttc ttt      240 
Asp Ser Ile Asp Glu Asn Ser Met Thr Tyr Val Ala Asp Val Phe Phe 
 65                  70                  75                  80 

gca cag acg tgg aag gat cat cgc ctg cga ttg ccg gag aat atg aca      288 
Ala Gln Thr Trp Lys Asp His Arg Leu Arg Leu Pro Glu Asn Met Thr 
                 85                  90                  95 

cag gaa tac cgc ctg ctc gag gtg gac tgg cta aaa aat atg tgg cgg      336 
Gln Glu Tyr Arg Leu Leu Glu Val Asp Trp Leu Lys Asn Met Trp Arg 
            100                 105                 110 

ccg gat tcg ttt ttc aaa aac gcc aaa tcg gtg acc ttt cag acc atg      384 
Pro Asp Ser Phe Phe Lys Asn Ala Lys Ser Val Thr Phe Gln Thr Met 
        115                 120                 125 

aca ata ccc aat cac tat atg tgg ctg tac aag gat aag acc att ctg      432 
Thr Ile Pro Asn His Tyr Met Trp Leu Tyr Lys Asp Lys Thr Ile Leu 
    130                 135                 140 

tac atg gtc aaa cta aca ctg aag ctg tcc tgc atc atg aac ttc gcc      480 
Tyr Met Val Lys Leu Thr Leu Lys Leu Ser Cys Ile Met Asn Phe Ala 
145                 150                 155                 160 

att tat cct cat gat aca cag gag tgc aag ctg caa atg gaa agc ctg      528 
Ile Tyr Pro His Asp Thr Gln Glu Cys Lys Leu Gln Met Glu Ser Leu 
                165                 170                 175 

tcc cac acc acg gat gac ttg ata ttc cag tgg gat cca aca acg ccc      576 
Ser His Thr Thr Asp Asp Leu Ile Phe Gln Trp Asp Pro Thr Thr Pro 
            180                 185                 190 

ctt gtg gtt gat gaa aac atc gaa ctg ccg cag gtg gcc ctc atc cga      624 
Leu Val Val Asp Glu Asn Ile Glu Leu Pro Gln Val Ala Leu Ile Arg 
        195                 200                 205 

aat gaa acg gcg gac tgt acc caa gtt tat tcc act ggc aac ttc aca      672 
Asn Glu Thr Ala Asp Cys Thr Gln Val Tyr Ser Thr Gly Asn Phe Thr 
    210                 215                 220 

tgc ctg gag gtg gtg ttc acc ctt aag cgt cgt ttg gtt tac tac gtt      720 
Cys Leu Glu Val Val Phe Thr Leu Lys Arg Arg Leu Val Tyr Tyr Val 
225                 230                 235                 240 

ttc aac acc tac att ccc acc tgc atg ata gtg atc atg tca tgg gta      768 
Phe Asn Thr Tyr Ile Pro Thr Cys Met Ile Val Ile Met Ser Trp Val 
                245                 250                 255 

tcc ttc tgg atc aaa ccg gag gcg gca cca gcc cgt gtg act ctg ggt      816 
Ser Phe Trp Ile Lys Pro Glu Ala Ala Pro Ala Arg Val Thr Leu Gly 
            260                 265                 270 

gtc acc tcc ttg cta acg ctt tcc acg caa cac gcc aaa tcg cag tcg      864 
Val Thr Ser Leu Leu Thr Leu Ser Thr Gln His Ala Lys Ser Gln Ser 
        275                 280                 285 

tct ttg cca cct gtt tcc tat ctc aag gca gtg gac gcc ttt atg tcc      912 
Ser Leu Pro Pro Val Ser Tyr Leu Lys Ala Val Asp Ala Phe Met Ser 
    290                 295                 300 

gtt tgc acg gtg ttc gtg ttt atg gcc ctc atg gag tat tgt cta ata      960 
Val Cys Thr Val Phe Val Phe Met Ala Leu Met Glu Tyr Cys Leu Ile 
305                 310                 315                 320 

aac atc gtc ctg agc gac acg ccc att ccc aag ccg atg gcc tat cca     1008 
Asn Ile Val Leu Ser Asp Thr Pro Ile Pro Lys Pro Met Ala Tyr Pro 
                325                 330                 335 

ccc aaa cct gtg gcg gga gat ggg ccc aag aaa gag ggc gag ggt gct     1056 
Pro Lys Pro Val Ala Gly Asp Gly Pro Lys Lys Glu Gly Glu Gly Ala 
            340                 345                 350 

cct cct ggg ggc agc aac tcg acg gcc agc aag caa caa gcc acc atg     1104 
Pro Pro Gly Gly Ser Asn Ser Thr Ala Ser Lys Gln Gln Ala Thr Met 
        355                 360                 365 

ttg cca ctg gcc gat gaa aag atc gag aaa att gag aag atc ttt gac     1152 
Leu Pro Leu Ala Asp Glu Lys Ile Glu Lys Ile Glu Lys Ile Phe Asp 
    370                 375                 380 

gag atg acc aag aat aga agg att gta acc acc aca cgc cgc gtg gtg     1200 
Glu Met Thr Lys Asn Arg Arg Ile Val Thr Thr Thr Arg Arg Val Val 
385                 390                 395                 400 

cgt ccg cca ttg gac gcc gat ggt ccg tgg att ccg cga cag gag tcg     1248 
Arg Pro Pro Leu Asp Ala Asp Gly Pro Trp Ile Pro Arg Gln Glu Ser 
                405                 410                 415 

cgg ata ata ctg acc ccg act atc gct ccg ccg cca ccg ccc cct cag     1296 
Arg Ile Ile Leu Thr Pro Thr Ile Ala Pro Pro Pro Pro Pro Pro Gln 
            420                 425                 430 

cca gcg gca ccg gaa ccg gaa ctg ccc aag ccg aaa ctc aca ccc gcc     1344 
Pro Ala Ala Pro Glu Pro Glu Leu Pro Lys Pro Lys Leu Thr Pro Ala 
        435                 440                 445 

cag gag cgg ctc aag cgg gct ata tat ata gat cgg tcc tcg cgc gtc     1392 
Gln Glu Arg Leu Lys Arg Ala Ile Tyr Ile Asp Arg Ser Ser Arg Val 
    450                 455                 460 

ctt ttc ccc gcc ctc ttc gcc agt ctg aat ggc atc tac tgg tgt caa     1440 
Leu Phe Pro Ala Leu Phe Ala Ser Leu Asn Gly Ile Tyr Trp Cys Gln 
465                 470                 475                 480 

ctt tgg atg gaa caa tgg aac ttg ctc gat ttt cta ccg cct gca gtc     1488 
Leu Trp Met Glu Gln Trp Asn Leu Leu Asp Phe Leu Pro Pro Ala Val 
                485                 490                 495 

ttc aaa cag ccg cag ggt gaa gag aaa cag act tat gaa tac cca att     1536 
Phe Lys Gln Pro Gln Gly Glu Glu Lys Gln Thr Tyr Glu Tyr Pro Ile 
            500                 505                 510 

aat tat gtt ggt cac acg ctc cac act ttt gcc ttt tca cgg tcg tta     1584 
Asn Tyr Val Gly His Thr Leu His Thr Phe Ala Phe Ser Arg Ser Leu 
        515                 520                 525 

gtg acg ctc gag caa aaa cta tga                                     1608 
Val Thr Leu Glu Gln Lys Leu 
    530                 535 

 
           
             10  
             535  
             PRT  
             Drosophila melanogaster  
           
            10 

Met Val Phe Gln Ile Ile Ile Leu Val Ile Cys Thr Ile Cys Met Lys 
  1               5                  10                  15 

His Tyr Ala Lys Gly Glu Phe Gln Gln Ser Leu Ala Ile Thr Asp Ile 
             20                  25                  30 

Leu Pro Glu Asp Ile Lys Arg Tyr Asp Lys Met Arg Pro Pro Lys Lys 
         35                  40                  45 

Glu Gly Gln Pro Thr Ile Val Tyr Phe His Val Thr Val Met Gly Leu 
     50                  55                  60 

Asp Ser Ile Asp Glu Asn Ser Met Thr Tyr Val Ala Asp Val Phe Phe 
 65                  70                  75                  80 

Ala Gln Thr Trp Lys Asp His Arg Leu Arg Leu Pro Glu Asn Met Thr 
                 85                  90                  95 

Gln Glu Tyr Arg Leu Leu Glu Val Asp Trp Leu Lys Asn Met Trp Arg 
            100                 105                 110 

Pro Asp Ser Phe Phe Lys Asn Ala Lys Ser Val Thr Phe Gln Thr Met 
        115                 120                 125 

Thr Ile Pro Asn His Tyr Met Trp Leu Tyr Lys Asp Lys Thr Ile Leu 
    130                 135                 140 

Tyr Met Val Lys Leu Thr Leu Lys Leu Ser Cys Ile Met Asn Phe Ala 
145                 150                 155                 160 

Ile Tyr Pro His Asp Thr Gln Glu Cys Lys Leu Gln Met Glu Ser Leu 
                165                 170                 175 

Ser His Thr Thr Asp Asp Leu Ile Phe Gln Trp Asp Pro Thr Thr Pro 
            180                 185                 190 

Leu Val Val Asp Glu Asn Ile Glu Leu Pro Gln Val Ala Leu Ile Arg 
        195                 200                 205 

Asn Glu Thr Ala Asp Cys Thr Gln Val Tyr Ser Thr Gly Asn Phe Thr 
    210                 215                 220 

Cys Leu Glu Val Val Phe Thr Leu Lys Arg Arg Leu Val Tyr Tyr Val 
225                 230                 235                 240 

Phe Asn Thr Tyr Ile Pro Thr Cys Met Ile Val Ile Met Ser Trp Val 
                245                 250                 255 

Ser Phe Trp Ile Lys Pro Glu Ala Ala Pro Ala Arg Val Thr Leu Gly 
            260                 265                 270 

Val Thr Ser Leu Leu Thr Leu Ser Thr Gln His Ala Lys Ser Gln Ser 
        275                 280                 285 

Ser Leu Pro Pro Val Ser Tyr Leu Lys Ala Val Asp Ala Phe Met Ser 
    290                 295                 300 

Val Cys Thr Val Phe Val Phe Met Ala Leu Met Glu Tyr Cys Leu Ile 
305                 310                 315                 320 

Asn Ile Val Leu Ser Asp Thr Pro Ile Pro Lys Pro Met Ala Tyr Pro 
                325                 330                 335 

Pro Lys Pro Val Ala Gly Asp Gly Pro Lys Lys Glu Gly Glu Gly Ala 
            340                 345                 350 

Pro Pro Gly Gly Ser Asn Ser Thr Ala Ser Lys Gln Gln Ala Thr Met 
        355                 360                 365 

Leu Pro Leu Ala Asp Glu Lys Ile Glu Lys Ile Glu Lys Ile Phe Asp 
    370                 375                 380 

Glu Met Thr Lys Asn Arg Arg Ile Val Thr Thr Thr Arg Arg Val Val 
385                 390                 395                 400 

Arg Pro Pro Leu Asp Ala Asp Gly Pro Trp Ile Pro Arg Gln Glu Ser 
                405                 410                 415 

Arg Ile Ile Leu Thr Pro Thr Ile Ala Pro Pro Pro Pro Pro Pro Gln 
            420                 425                 430 

Pro Ala Ala Pro Glu Pro Glu Leu Pro Lys Pro Lys Leu Thr Pro Ala 
        435                 440                 445 

Gln Glu Arg Leu Lys Arg Ala Ile Tyr Ile Asp Arg Ser Ser Arg Val 
    450                 455                 460 

Leu Phe Pro Ala Leu Phe Ala Ser Leu Asn Gly Ile Tyr Trp Cys Gln 
465                 470                 475                 480 

Leu Trp Met Glu Gln Trp Asn Leu Leu Asp Phe Leu Pro Pro Ala Val 
                485                 490                 495 

Phe Lys Gln Pro Gln Gly Glu Glu Lys Gln Thr Tyr Glu Tyr Pro Ile 
            500                 505                 510 

Asn Tyr Val Gly His Thr Leu His Thr Phe Ala Phe Ser Arg Ser Leu 
        515                 520                 525 

Val Thr Leu Glu Gln Lys Leu 
    530                 535 

 
           
             11  
             1458  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1455)  
             
           
            11 

atg gtg ttc caa ata ata atc ctg gtg atc tgc acc atc tgc atg aag       48 
Met Val Phe Gln Ile Ile Ile Leu Val Ile Cys Thr Ile Cys Met Lys 
  1               5                  10                  15 

cac tac gcc aaa ggg gag ttt caa caa agt ctg gcc ata acc gac atc       96 
His Tyr Ala Lys Gly Glu Phe Gln Gln Ser Leu Ala Ile Thr Asp Ile 
             20                  25                  30 

ctg ccc gag gac atc aag cgt tac gac aag atg aga ccg ccg aag aaa      144 
Leu Pro Glu Asp Ile Lys Arg Tyr Asp Lys Met Arg Pro Pro Lys Lys 
         35                  40                  45 

gag ggt cag ccg acg ata gtc tac ttc cat gtg acg gtg atg ggt ctg      192 
Glu Gly Gln Pro Thr Ile Val Tyr Phe His Val Thr Val Met Gly Leu 
     50                  55                  60 

gac tcc att gat gag aac tcg atg act tat gtg gcg gat gtg ttc ttt      240 
Asp Ser Ile Asp Glu Asn Ser Met Thr Tyr Val Ala Asp Val Phe Phe 
 65                  70                  75                  80 

gca cag acg tgg aag gat cat cgc ctg cga ttg ccg gag aat atg aca      288 
Ala Gln Thr Trp Lys Asp His Arg Leu Arg Leu Pro Glu Asn Met Thr 
                 85                  90                  95 

cag gaa tac cgc ctg ctc gag gtg gac tgg cta aaa aat atg tgg cgg      336 
Gln Glu Tyr Arg Leu Leu Glu Val Asp Trp Leu Lys Asn Met Trp Arg 
            100                 105                 110 

ccg gat tcg ttt ttc aaa aac gcc aaa tcg gtg acc ttt cag acc atg      384 
Pro Asp Ser Phe Phe Lys Asn Ala Lys Ser Val Thr Phe Gln Thr Met 
        115                 120                 125 

aca ata ccc aat cac tat atg tgg ctg tac aag gat aag acc att ctg      432 
Thr Ile Pro Asn His Tyr Met Trp Leu Tyr Lys Asp Lys Thr Ile Leu 
    130                 135                 140 

tac atg gtc aaa cta aca ctg aag ctg tcc tgc atc atg aac ttc gcc      480 
Tyr Met Val Lys Leu Thr Leu Lys Leu Ser Cys Ile Met Asn Phe Ala 
145                 150                 155                 160 

att tat cct cat gat aca cag gag tgc aag ctg caa atg gaa agc ctg      528 
Ile Tyr Pro His Asp Thr Gln Glu Cys Lys Leu Gln Met Glu Ser Leu 
                165                 170                 175 

tcc cac acc acg gat gac ttg ata ttc cag tgg gat cca aca acg ccc      576 
Ser His Thr Thr Asp Asp Leu Ile Phe Gln Trp Asp Pro Thr Thr Pro 
            180                 185                 190 

ctt gtg gtt gat gaa aac atc gaa ctg ccg cag gtg gcc ctc atc cga      624 
Leu Val Val Asp Glu Asn Ile Glu Leu Pro Gln Val Ala Leu Ile Arg 
        195                 200                 205 

aat gaa acg gcg gac tgt acc caa gtt tat tcc act ggc aac ttc aca      672 
Asn Glu Thr Ala Asp Cys Thr Gln Val Tyr Ser Thr Gly Asn Phe Thr 
    210                 215                 220 

tgc ctg gag gtg gtg ttc acc ctt aag cgt cgt ttg gtt tac tac gtt      720 
Cys Leu Glu Val Val Phe Thr Leu Lys Arg Arg Leu Val Tyr Tyr Val 
225                 230                 235                 240 

ttc aac acc tac att ccc acc tgc atg ata gtg atc atg tca tgg gta      768 
Phe Asn Thr Tyr Ile Pro Thr Cys Met Ile Val Ile Met Ser Trp Val 
                245                 250                 255 

tcc ttc tgg atc aaa ccg gag gcg gca cca gcc cgt gtg act ctg ggt      816 
Ser Phe Trp Ile Lys Pro Glu Ala Ala Pro Ala Arg Val Thr Leu Gly 
            260                 265                 270 

gtc acc tcc ttg cta acg ctt tcc acg caa cac gcc aaa tcg cag tcg      864 
Val Thr Ser Leu Leu Thr Leu Ser Thr Gln His Ala Lys Ser Gln Ser 
        275                 280                 285 

tct ttg cca cct gtt tcc tat ctc aag gca gtg gac gcc ttt atg tcc      912 
Ser Leu Pro Pro Val Ser Tyr Leu Lys Ala Val Asp Ala Phe Met Ser 
    290                 295                 300 

gtt tgc acg gtg ttc gtg ttt atg gcc ctc atg gag tat tgt cta ata      960 
Val Cys Thr Val Phe Val Phe Met Ala Leu Met Glu Tyr Cys Leu Ile 
305                 310                 315                 320 

aac atc gtc ctg agc gac acg ccc att ccc aag ccg atg gcc tat cca     1008 
Asn Ile Val Leu Ser Asp Thr Pro Ile Pro Lys Pro Met Ala Tyr Pro 
                325                 330                 335 

ccc aaa cct gtg gcg gga gat ggg ccc aag aaa gag ggc gag ggt gct     1056 
Pro Lys Pro Val Ala Gly Asp Gly Pro Lys Lys Glu Gly Glu Gly Ala 
            340                 345                 350 

cct cct ggg ggc agc aac tcg acg gcc agc aag caa caa gcc acc atg     1104 
Pro Pro Gly Gly Ser Asn Ser Thr Ala Ser Lys Gln Gln Ala Thr Met 
        355                 360                 365 

ttg cca ctg gcc gat gaa aag atc gag aaa att gag aag atc ttt gac     1152 
Leu Pro Leu Ala Asp Glu Lys Ile Glu Lys Ile Glu Lys Ile Phe Asp 
    370                 375                 380 

gag atg acc aag aat aga agg att gta acc acc aca cgc cgc gtg gtg     1200 
Glu Met Thr Lys Asn Arg Arg Ile Val Thr Thr Thr Arg Arg Val Val 
385                 390                 395                 400 

cgt ccg cca ttg gac gcc gat ggt ccg tgg att ccg cga cag gag tcg     1248 
Arg Pro Pro Leu Asp Ala Asp Gly Pro Trp Ile Pro Arg Gln Glu Ser 
                405                 410                 415 

cgg ata ata ctg acc ccg act atc gct ccg ccg cca ccg ccc cct cag     1296 
Arg Ile Ile Leu Thr Pro Thr Ile Ala Pro Pro Pro Pro Pro Pro Gln 
            420                 425                 430 

cca gcg gca ccg gaa ccg gaa ctg ccc aag ccg aaa ctc aca ccc gcc     1344 
Pro Ala Ala Pro Glu Pro Glu Leu Pro Lys Pro Lys Leu Thr Pro Ala 
        435                 440                 445 

cag gag cgg ctc aag cgg gct ata tat ata gat cgg tcc tcg cgc gtc     1392 
Gln Glu Arg Leu Lys Arg Ala Ile Tyr Ile Asp Arg Ser Ser Arg Val 
    450                 455                 460 

ctt ttc ccc gcc ctc ttc gcc agt ctg aat ggc atc tac tgg tgt gtg     1440 
Leu Phe Pro Ala Leu Phe Ala Ser Leu Asn Gly Ile Tyr Trp Cys Val 
465                 470                 475                 480 

ttc tac gag tat cta taa                                             1458 
Phe Tyr Glu Tyr Leu 
                485 

 
           
             12  
             485  
             PRT  
             Drosophila melanogaster  
           
            12 

Met Val Phe Gln Ile Ile Ile Leu Val Ile Cys Thr Ile Cys Met Lys 
  1               5                  10                  15 

His Tyr Ala Lys Gly Glu Phe Gln Gln Ser Leu Ala Ile Thr Asp Ile 
             20                  25                  30 

Leu Pro Glu Asp Ile Lys Arg Tyr Asp Lys Met Arg Pro Pro Lys Lys 
         35                  40                  45 

Glu Gly Gln Pro Thr Ile Val Tyr Phe His Val Thr Val Met Gly Leu 
     50                  55                  60 

Asp Ser Ile Asp Glu Asn Ser Met Thr Tyr Val Ala Asp Val Phe Phe 
 65                  70                  75                  80 

Ala Gln Thr Trp Lys Asp His Arg Leu Arg Leu Pro Glu Asn Met Thr 
                 85                  90                  95 

Gln Glu Tyr Arg Leu Leu Glu Val Asp Trp Leu Lys Asn Met Trp Arg 
            100                 105                 110 

Pro Asp Ser Phe Phe Lys Asn Ala Lys Ser Val Thr Phe Gln Thr Met 
        115                 120                 125 

Thr Ile Pro Asn His Tyr Met Trp Leu Tyr Lys Asp Lys Thr Ile Leu 
    130                 135                 140 

Tyr Met Val Lys Leu Thr Leu Lys Leu Ser Cys Ile Met Asn Phe Ala 
145                 150                 155                 160 

Ile Tyr Pro His Asp Thr Gln Glu Cys Lys Leu Gln Met Glu Ser Leu 
                165                 170                 175 

Ser His Thr Thr Asp Asp Leu Ile Phe Gln Trp Asp Pro Thr Thr Pro 
            180                 185                 190 

Leu Val Val Asp Glu Asn Ile Glu Leu Pro Gln Val Ala Leu Ile Arg 
        195                 200                 205 

Asn Glu Thr Ala Asp Cys Thr Gln Val Tyr Ser Thr Gly Asn Phe Thr 
    210                 215                 220 

Cys Leu Glu Val Val Phe Thr Leu Lys Arg Arg Leu Val Tyr Tyr Val 
225                 230                 235                 240 

Phe Asn Thr Tyr Ile Pro Thr Cys Met Ile Val Ile Met Ser Trp Val 
                245                 250                 255 

Ser Phe Trp Ile Lys Pro Glu Ala Ala Pro Ala Arg Val Thr Leu Gly 
            260                 265                 270 

Val Thr Ser Leu Leu Thr Leu Ser Thr Gln His Ala Lys Ser Gln Ser 
        275                 280                 285 

Ser Leu Pro Pro Val Ser Tyr Leu Lys Ala Val Asp Ala Phe Met Ser 
    290                 295                 300 

Val Cys Thr Val Phe Val Phe Met Ala Leu Met Glu Tyr Cys Leu Ile 
305                 310                 315                 320 

Asn Ile Val Leu Ser Asp Thr Pro Ile Pro Lys Pro Met Ala Tyr Pro 
                325                 330                 335 

Pro Lys Pro Val Ala Gly Asp Gly Pro Lys Lys Glu Gly Glu Gly Ala 
            340                 345                 350 

Pro Pro Gly Gly Ser Asn Ser Thr Ala Ser Lys Gln Gln Ala Thr Met 
        355                 360                 365 

Leu Pro Leu Ala Asp Glu Lys Ile Glu Lys Ile Glu Lys Ile Phe Asp 
    370                 375                 380 

Glu Met Thr Lys Asn Arg Arg Ile Val Thr Thr Thr Arg Arg Val Val 
385                 390                 395                 400 

Arg Pro Pro Leu Asp Ala Asp Gly Pro Trp Ile Pro Arg Gln Glu Ser 
                405                 410                 415 

Arg Ile Ile Leu Thr Pro Thr Ile Ala Pro Pro Pro Pro Pro Pro Gln 
            420                 425                 430 

Pro Ala Ala Pro Glu Pro Glu Leu Pro Lys Pro Lys Leu Thr Pro Ala 
        435                 440                 445 

Gln Glu Arg Leu Lys Arg Ala Ile Tyr Ile Asp Arg Ser Ser Arg Val 
    450                 455                 460 

Leu Phe Pro Ala Leu Phe Ala Ser Leu Asn Gly Ile Tyr Trp Cys Val 
465                 470                 475                 480 

Phe Tyr Glu Tyr Leu 
                485 

 
           
             13  
             1491  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1488)  
             
           
            13 

atg gcc aat gga tcg gtg gtg gtg tcg cct ttg aac acc acg gat gct       48 
Met Ala Asn Gly Ser Val Val Val Ser Pro Leu Asn Thr Thr Asp Ala 
  1               5                  10                  15 

ttc agt gtg tcc atc aac ctg tcg caa tcg act gtg aac aat tgt cct       96 
Phe Ser Val Ser Ile Asn Leu Ser Gln Ser Thr Val Asn Asn Cys Pro 
             20                  25                  30 

tcg ctg aaa aac gca gag tcc atg gcg ctg atg gag ctg ctg acg aga      144 
Ser Leu Lys Asn Ala Glu Ser Met Ala Leu Met Glu Leu Leu Thr Arg 
         35                  40                  45 

cta acc gcc ccc tgt cgc tat gac agg atg gtt cca ccc gtg gtc cac      192 
Leu Thr Ala Pro Cys Arg Tyr Asp Arg Met Val Pro Pro Val Val His 
     50                  55                  60 

aac aaa gat ggt gag gag gta ccc atg gac ata tat gcc cgg ttt tac      240 
Asn Lys Asp Gly Glu Glu Val Pro Met Asp Ile Tyr Ala Arg Phe Tyr 
 65                  70                  75                  80 

ata tat gtg atg aag aac ctg gac tcg agt gac ctg cag ttt acg gtg      288 
Ile Tyr Val Met Lys Asn Leu Asp Ser Ser Asp Leu Gln Phe Thr Val 
                 85                  90                  95 

cag ggt ctg ctg cag ttg cga tac ctg gac ccg cgc ctg gcc ttc tcc      336 
Gln Gly Leu Leu Gln Leu Arg Tyr Leu Asp Pro Arg Leu Ala Phe Ser 
            100                 105                 110 

agc tat ctg cct aac cga agg cag ccc ata atg ggg gag tcg gaa ctg      384 
Ser Tyr Leu Pro Asn Arg Arg Gln Pro Ile Met Gly Glu Ser Glu Leu 
        115                 120                 125 

aag aag atg ctc tgg gtg cca cat ata ttc ctg acc aac gaa cag gcc      432 
Lys Lys Met Leu Trp Val Pro His Ile Phe Leu Thr Asn Glu Gln Ala 
    130                 135                 140 

tcc act gtc ctg ggc acc agc gcc aag gac gag ctg acc agc att tat      480 
Ser Thr Val Leu Gly Thr Ser Ala Lys Asp Glu Leu Thr Ser Ile Tyr 
145                 150                 155                 160 

ccg aat ggc aca gtt ctt aca tcc acg cgg ctg cag gcc aca ctg tac      528 
Pro Asn Gly Thr Val Leu Thr Ser Thr Arg Leu Gln Ala Thr Leu Tyr 
                165                 170                 175 

tgc tgg atg aac ttc cag aag ttt ccg ttt gat gag cag aag tgt aag      576 
Cys Trp Met Asn Phe Gln Lys Phe Pro Phe Asp Glu Gln Lys Cys Lys 
            180                 185                 190 

acc aca ttg gaa agt tgg atg tac aac acc acg ctg gtg caa ctc cac      624 
Thr Thr Leu Glu Ser Trp Met Tyr Asn Thr Thr Leu Val Gln Leu His 
        195                 200                 205 

tgg gag acc gat aac cca gtg agt ttc gac aag caa ctt cag ctg acg      672 
Trp Glu Thr Asp Asn Pro Val Ser Phe Asp Lys Gln Leu Gln Leu Thr 
    210                 215                 220 

gaa tac aac cta att ggg tcg ctg tac aac gaa tcc atc cga gtg tcc      720 
Glu Tyr Asn Leu Ile Gly Ser Leu Tyr Asn Glu Ser Ile Arg Val Ser 
225                 230                 235                 240 

aac gaa tcc tac atg tcc cat ggc tcc ttg gag ggc aac tac agc atc      768 
Asn Glu Ser Tyr Met Ser His Gly Ser Leu Glu Gly Asn Tyr Ser Ile 
                245                 250                 255 

att agc ttc acc gtt ctg ctt act cgg gaa gtg ggc tac tac gtg atc      816 
Ile Ser Phe Thr Val Leu Leu Thr Arg Glu Val Gly Tyr Tyr Val Ile 
            260                 265                 270 

gac tac ttt ctg ccc tcg atc atg ata gtc acc att tcg tgg gtg tcc      864 
Asp Tyr Phe Leu Pro Ser Ile Met Ile Val Thr Ile Ser Trp Val Ser 
        275                 280                 285 

ttc tgg ctg cag gcg gat caa acc ccc gca agg act act ctg ggc tgc      912 
Phe Trp Leu Gln Ala Asp Gln Thr Pro Ala Arg Thr Thr Leu Gly Cys 
    290                 295                 300 

acc acg ctc cta tcc ttc atc act ctg tcc ttg tcc cag gag aac aat      960 
Thr Thr Leu Leu Ser Phe Ile Thr Leu Ser Leu Ser Gln Glu Asn Asn 
305                 310                 315                 320 

ctg atg aag gtg agc tac gtg acc atg tcg gag gtg tgg ttc ctg gtc     1008 
Leu Met Lys Val Ser Tyr Val Thr Met Ser Glu Val Trp Phe Leu Val 
                325                 330                 335 

tgc acc atc ttc att ttc ggc agc ctg gtg gag ttc gcc ttt gtc aac     1056 
Cys Thr Ile Phe Ile Phe Gly Ser Leu Val Glu Phe Ala Phe Val Asn 
            340                 345                 350 

acc atc tgg agg cga aac aac gat ctg caa ctc aag aag cga acc acc     1104 
Thr Ile Trp Arg Arg Asn Asn Asp Leu Gln Leu Lys Lys Arg Thr Thr 
        355                 360                 365 

aag tat ata gtc aag tcc aca ttt gtc cca cat ctg aag aaa cat cgg     1152 
Lys Tyr Ile Val Lys Ser Thr Phe Val Pro His Leu Lys Lys His Arg 
    370                 375                 380 

cgg cat gga tat aga agg acc gat agc act atg agc acc atg agc acc     1200 
Arg His Gly Tyr Arg Arg Thr Asp Ser Thr Met Ser Thr Met Ser Thr 
385                 390                 395                 400 

acc agc atg gac aag acc tgc ggt ccc aac aac acc gtg atc acc ata     1248 
Thr Ser Met Asp Lys Thr Cys Gly Pro Asn Asn Thr Val Ile Thr Ile 
                405                 410                 415 

gag aca cca att att att gga ggc agt ctt agt cgc gag gac tcg gcc     1296 
Glu Thr Pro Ile Ile Ile Gly Gly Ser Leu Ser Arg Glu Asp Ser Ala 
            420                 425                 430 

att agc ttg gac gag cag gac gag acc tcc acc tcg gag tcc agc gat     1344 
Ile Ser Leu Asp Glu Gln Asp Glu Thr Ser Thr Ser Glu Ser Ser Asp 
        435                 440                 445 

tcg tcg aag gag aaa ccc gcg cag acc ttc gcc acc atg aca ccc aag     1392 
Ser Ser Lys Glu Lys Pro Ala Gln Thr Phe Ala Thr Met Thr Pro Lys 
    450                 455                 460 

gag gtg tcc ctg tgg atc gac cgc aag atg cgg ttc gtc ttc cct ctg     1440 
Glu Val Ser Leu Trp Ile Asp Arg Lys Met Arg Phe Val Phe Pro Leu 
465                 470                 475                 480 

tcc ttc atc gtg ttc aac gcc ttg ttt tgg acc ctg gtc tac tgc ctt     1488 
Ser Phe Ile Val Phe Asn Ala Leu Phe Trp Thr Leu Val Tyr Cys Leu 
                485                 490                 495 
tga                                                                 1491 

 
           
             14  
             496  
             PRT  
             Drosophila melanogaster  
           
            14 

Met Ala Asn Gly Ser Val Val Val Ser Pro Leu Asn Thr Thr Asp Ala 
  1               5                  10                  15 

Phe Ser Val Ser Ile Asn Leu Ser Gln Ser Thr Val Asn Asn Cys Pro 
             20                  25                  30 

Ser Leu Lys Asn Ala Glu Ser Met Ala Leu Met Glu Leu Leu Thr Arg 
         35                  40                  45 

Leu Thr Ala Pro Cys Arg Tyr Asp Arg Met Val Pro Pro Val Val His 
     50                  55                  60 

Asn Lys Asp Gly Glu Glu Val Pro Met Asp Ile Tyr Ala Arg Phe Tyr 
 65                  70                  75                  80 

Ile Tyr Val Met Lys Asn Leu Asp Ser Ser Asp Leu Gln Phe Thr Val 
                 85                  90                  95 

Gln Gly Leu Leu Gln Leu Arg Tyr Leu Asp Pro Arg Leu Ala Phe Ser 
            100                 105                 110 

Ser Tyr Leu Pro Asn Arg Arg Gln Pro Ile Met Gly Glu Ser Glu Leu 
        115                 120                 125 

Lys Lys Met Leu Trp Val Pro His Ile Phe Leu Thr Asn Glu Gln Ala 
    130                 135                 140 

Ser Thr Val Leu Gly Thr Ser Ala Lys Asp Glu Leu Thr Ser Ile Tyr 
145                 150                 155                 160 

Pro Asn Gly Thr Val Leu Thr Ser Thr Arg Leu Gln Ala Thr Leu Tyr 
                165                 170                 175 

Cys Trp Met Asn Phe Gln Lys Phe Pro Phe Asp Glu Gln Lys Cys Lys 
            180                 185                 190 

Thr Thr Leu Glu Ser Trp Met Tyr Asn Thr Thr Leu Val Gln Leu His 
        195                 200                 205 

Trp Glu Thr Asp Asn Pro Val Ser Phe Asp Lys Gln Leu Gln Leu Thr 
    210                 215                 220 

Glu Tyr Asn Leu Ile Gly Ser Leu Tyr Asn Glu Ser Ile Arg Val Ser 
225                 230                 235                 240 

Asn Glu Ser Tyr Met Ser His Gly Ser Leu Glu Gly Asn Tyr Ser Ile 
                245                 250                 255 

Ile Ser Phe Thr Val Leu Leu Thr Arg Glu Val Gly Tyr Tyr Val Ile 
            260                 265                 270 

Asp Tyr Phe Leu Pro Ser Ile Met Ile Val Thr Ile Ser Trp Val Ser 
        275                 280                 285 

Phe Trp Leu Gln Ala Asp Gln Thr Pro Ala Arg Thr Thr Leu Gly Cys 
    290                 295                 300 

Thr Thr Leu Leu Ser Phe Ile Thr Leu Ser Leu Ser Gln Glu Asn Asn 
305                 310                 315                 320 

Leu Met Lys Val Ser Tyr Val Thr Met Ser Glu Val Trp Phe Leu Val 
                325                 330                 335 

Cys Thr Ile Phe Ile Phe Gly Ser Leu Val Glu Phe Ala Phe Val Asn 
            340                 345                 350 

Thr Ile Trp Arg Arg Asn Asn Asp Leu Gln Leu Lys Lys Arg Thr Thr 
        355                 360                 365 

Lys Tyr Ile Val Lys Ser Thr Phe Val Pro His Leu Lys Lys His Arg 
    370                 375                 380 

Arg His Gly Tyr Arg Arg Thr Asp Ser Thr Met Ser Thr Met Ser Thr 
385                 390                 395                 400 

Thr Ser Met Asp Lys Thr Cys Gly Pro Asn Asn Thr Val Ile Thr Ile 
                405                 410                 415 

Glu Thr Pro Ile Ile Ile Gly Gly Ser Leu Ser Arg Glu Asp Ser Ala 
            420                 425                 430 

Ile Ser Leu Asp Glu Gln Asp Glu Thr Ser Thr Ser Glu Ser Ser Asp 
        435                 440                 445 

Ser Ser Lys Glu Lys Pro Ala Gln Thr Phe Ala Thr Met Thr Pro Lys 
    450                 455                 460 

Glu Val Ser Leu Trp Ile Asp Arg Lys Met Arg Phe Val Phe Pro Leu 
465                 470                 475                 480 

Ser Phe Ile Val Phe Asn Ala Leu Phe Trp Thr Leu Val Tyr Cys Leu 
                485                 490                 495 

 
           
             15  
             1353  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1350)  
             
           
            15 

atg ttt ctg ttc gca gaa tac gac tct gat gga aaa cga ctg ccc att       48 
Met Phe Leu Phe Ala Glu Tyr Asp Ser Asp Gly Lys Arg Leu Pro Ile 
  1               5                  10                  15 

gtg gtg aag acg cgt att tat gtg tac ttc ctg cag aac ctc aac tcc       96 
Val Val Lys Thr Arg Ile Tyr Val Tyr Phe Leu Gln Asn Leu Asn Ser 
             20                  25                  30 

gac ctg ctg cag ttc aag atg cac gcg ctg ttg cag ctg cga ttt cag      144 
Asp Leu Leu Gln Phe Lys Met His Ala Leu Leu Gln Leu Arg Phe Gln 
         35                  40                  45 

gac aag cgg ctg gct tac aag gcc ttc aat cgc agc gac aac atc ctg      192 
Asp Lys Arg Leu Ala Tyr Lys Ala Phe Asn Arg Ser Asp Asn Ile Leu 
     50                  55                  60 

ggc cag aag cac ctg agc gaa cgc ctc tgg ctg ccg cac atc ttc ttt      240 
Gly Gln Lys His Leu Ser Glu Arg Leu Trp Leu Pro His Ile Phe Phe 
 65                  70                  75                  80 

gcc aac gaa cga gag tcc agt atc ctg ggc acg gac gag aag gac gtc      288 
Ala Asn Glu Arg Glu Ser Ser Ile Leu Gly Thr Asp Glu Lys Asp Val 
                 85                  90                  95 

ctg act tcg ctt tcg ccc gag gga aac gtg atc atc tcc acg cgc atg      336 
Leu Thr Ser Leu Ser Pro Glu Gly Asn Val Ile Ile Ser Thr Arg Met 
            100                 105                 110 

cag gcc agt ctc tac tgc tgg atg aac ttt cag aag ttt ccc ttt gac      384 
Gln Ala Ser Leu Tyr Cys Trp Met Asn Phe Gln Lys Phe Pro Phe Asp 
        115                 120                 125 

cag cag ttc tgc tcc acg gtc ctg gag agc tgg atg tac aac act tcc      432 
Gln Gln Phe Cys Ser Thr Val Leu Glu Ser Trp Met Tyr Asn Thr Ser 
    130                 135                 140 

gat ttg att ctg gag tgg gag ccg cac acg ccc atc tcc ttt gac ccg      480 
Asp Leu Ile Leu Glu Trp Glu Pro His Thr Pro Ile Ser Phe Asp Pro 
145                 150                 155                 160 

gaa atg agg ctc act gag tac aat atg gcc cag ttc tgg cac aac act      528 
Glu Met Arg Leu Thr Glu Tyr Asn Met Ala Gln Phe Trp His Asn Thr 
                165                 170                 175 

acg att gtg cag tcg gat ggg gac aat ctg cgg cat gga gct ttt gct      576 
Thr Ile Val Gln Ser Asp Gly Asp Asn Leu Arg His Gly Ala Phe Ala 
            180                 185                 190 

ggt aac tat agt tcg ctg agc ttt acg gtc aat ctg aag cga gaa att      624 
Gly Asn Tyr Ser Ser Leu Ser Phe Thr Val Asn Leu Lys Arg Glu Ile 
        195                 200                 205 

ggc ttc tat ttg ctc gac tat tac ctg ccc tcc atg atg atc gtg gcc      672 
Gly Phe Tyr Leu Leu Asp Tyr Tyr Leu Pro Ser Met Met Ile Val Ala 
    210                 215                 220 

atc tct tgg gtg tcc ttc tgg ctt cag gcg gac gca tct cct cca agg      720 
Ile Ser Trp Val Ser Phe Trp Leu Gln Ala Asp Ala Ser Pro Pro Arg 
225                 230                 235                 240 

att atg ctg gga acc agc acc atg ttg tcg ttc atc acg ctt tcc tca      768 
Ile Met Leu Gly Thr Ser Thr Met Leu Ser Phe Ile Thr Leu Ser Ser 
                245                 250                 255 

tcg cag agc aag aac ctg ccc aag gtg agc tac ata aag gtg tcg gag      816 
Ser Gln Ser Lys Asn Leu Pro Lys Val Ser Tyr Ile Lys Val Ser Glu 
            260                 265                 270 

gtg tgg tgc ctg ggc tgc acc ttc ttc atc ttc ggc agc ctg gtg gag      864 
Val Trp Cys Leu Gly Cys Thr Phe Phe Ile Phe Gly Ser Leu Val Glu 
        275                 280                 285 

ttt gcc ttt gtc aac acc att tgg cgc cgc aag gag aac att gag ctg      912 
Phe Ala Phe Val Asn Thr Ile Trp Arg Arg Lys Glu Asn Ile Glu Leu 
    290                 295                 300 

aag aag gtc aac agc aag tac atc ata aaa tcc aca ttg aca cca cga      960 
Lys Lys Val Asn Ser Lys Tyr Ile Ile Lys Ser Thr Leu Thr Pro Arg 
305                 310                 315                 320 

ccg gcc cgc cgt caa att ggc gga agt ttg agc aac gag tcc agg gct     1008 
Pro Ala Arg Arg Gln Ile Gly Gly Ser Leu Ser Asn Glu Ser Arg Ala 
                325                 330                 335 

aga tcg tgt tcc agt ttg gac aac att gtt tcc agc acg gag agc gtg     1056 
Arg Ser Cys Ser Ser Leu Asp Asn Ile Val Ser Ser Thr Glu Ser Val 
            340                 345                 350 

cgc aat ggc aat ggc act gtg aat cag ggc ttc aac aac tat ttg aca     1104 
Arg Asn Gly Asn Gly Thr Val Asn Gln Gly Phe Asn Asn Tyr Leu Thr 
        355                 360                 365 

gtg cat ccc aat tta ccc atc ata aga acg gag tgc gcc gag gca gat     1152 
Val His Pro Asn Leu Pro Ile Ile Arg Thr Glu Cys Ala Glu Ala Asp 
    370                 375                 380 

aca gtg tct atc tgc agt gcg cgt acg aac aac gat cat atc gtg gat     1200 
Thr Val Ser Ile Cys Ser Ala Arg Thr Asn Asn Asp His Ile Val Asp 
385                 390                 395                 400 

gtg gac aag gat aaa aag gac acg ccg ccc acc ttt acc acc atg aca     1248 
Val Asp Lys Asp Lys Lys Asp Thr Pro Pro Thr Phe Thr Thr Met Thr 
                405                 410                 415 

ccg cag gag atc gcc atg tgg ata gac cgg cgg tcg cga ttt ctt ttt     1296 
Pro Gln Glu Ile Ala Met Trp Ile Asp Arg Arg Ser Arg Phe Leu Phe 
            420                 425                 430 

ccg gcc atg ttc ctc gcc ttc aac gct ctg tat tgg acc ttc gtc tat     1344 
Pro Ala Met Phe Leu Ala Phe Asn Ala Leu Tyr Trp Thr Phe Val Tyr 
        435                 440                 445 

gtt ttg taa                                                         1353 
Val Leu 
    450 

 
           
             16  
             450  
             PRT  
             Drosophila melanogaster  
           
            16 

Met Phe Leu Phe Ala Glu Tyr Asp Ser Asp Gly Lys Arg Leu Pro Ile 
  1               5                  10                  15 

Val Val Lys Thr Arg Ile Tyr Val Tyr Phe Leu Gln Asn Leu Asn Ser 
             20                  25                  30 

Asp Leu Leu Gln Phe Lys Met His Ala Leu Leu Gln Leu Arg Phe Gln 
         35                  40                  45 

Asp Lys Arg Leu Ala Tyr Lys Ala Phe Asn Arg Ser Asp Asn Ile Leu 
     50                  55                  60 

Gly Gln Lys His Leu Ser Glu Arg Leu Trp Leu Pro His Ile Phe Phe 
 65                  70                  75                  80 

Ala Asn Glu Arg Glu Ser Ser Ile Leu Gly Thr Asp Glu Lys Asp Val 
                 85                  90                  95 

Leu Thr Ser Leu Ser Pro Glu Gly Asn Val Ile Ile Ser Thr Arg Met 
            100                 105                 110 

Gln Ala Ser Leu Tyr Cys Trp Met Asn Phe Gln Lys Phe Pro Phe Asp 
        115                 120                 125 

Gln Gln Phe Cys Ser Thr Val Leu Glu Ser Trp Met Tyr Asn Thr Ser 
    130                 135                 140 

Asp Leu Ile Leu Glu Trp Glu Pro His Thr Pro Ile Ser Phe Asp Pro 
145                 150                 155                 160 

Glu Met Arg Leu Thr Glu Tyr Asn Met Ala Gln Phe Trp His Asn Thr 
                165                 170                 175 

Thr Ile Val Gln Ser Asp Gly Asp Asn Leu Arg His Gly Ala Phe Ala 
            180                 185                 190 

Gly Asn Tyr Ser Ser Leu Ser Phe Thr Val Asn Leu Lys Arg Glu Ile 
        195                 200                 205 

Gly Phe Tyr Leu Leu Asp Tyr Tyr Leu Pro Ser Met Met Ile Val Ala 
    210                 215                 220 

Ile Ser Trp Val Ser Phe Trp Leu Gln Ala Asp Ala Ser Pro Pro Arg 
225                 230                 235                 240 

Ile Met Leu Gly Thr Ser Thr Met Leu Ser Phe Ile Thr Leu Ser Ser 
                245                 250                 255 

Ser Gln Ser Lys Asn Leu Pro Lys Val Ser Tyr Ile Lys Val Ser Glu 
            260                 265                 270 

Val Trp Cys Leu Gly Cys Thr Phe Phe Ile Phe Gly Ser Leu Val Glu 
        275                 280                 285 

Phe Ala Phe Val Asn Thr Ile Trp Arg Arg Lys Glu Asn Ile Glu Leu 
    290                 295                 300 

Lys Lys Val Asn Ser Lys Tyr Ile Ile Lys Ser Thr Leu Thr Pro Arg 
305                 310                 315                 320 

Pro Ala Arg Arg Gln Ile Gly Gly Ser Leu Ser Asn Glu Ser Arg Ala 
                325                 330                 335 

Arg Ser Cys Ser Ser Leu Asp Asn Ile Val Ser Ser Thr Glu Ser Val 
            340                 345                 350 

Arg Asn Gly Asn Gly Thr Val Asn Gln Gly Phe Asn Asn Tyr Leu Thr 
        355                 360                 365 

Val His Pro Asn Leu Pro Ile Ile Arg Thr Glu Cys Ala Glu Ala Asp 
    370                 375                 380 

Thr Val Ser Ile Cys Ser Ala Arg Thr Asn Asn Asp His Ile Val Asp 
385                 390                 395                 400 

Val Asp Lys Asp Lys Lys Asp Thr Pro Pro Thr Phe Thr Thr Met Thr 
                405                 410                 415 

Pro Gln Glu Ile Ala Met Trp Ile Asp Arg Arg Ser Arg Phe Leu Phe 
            420                 425                 430 

Pro Ala Met Phe Leu Ala Phe Asn Ala Leu Tyr Trp Thr Phe Val Tyr 
        435                 440                 445 

Val Leu 
    450 

 
           
             17  
             1257  
             DNA  
             Drosophila melanogaster  
             
               CDS  
               (1)..(1254)  
             
           
            17 

atg ctg agc gaa gcc acg gaa gcc cac atg aac tac aca gcc aag ccg       48 
Met Leu Ser Glu Ala Thr Glu Ala His Met Asn Tyr Thr Ala Lys Pro 
  1               5                  10                  15 

cga gta gtt ctt ccg cct aat tat gtc aag gaa ata cga ccg ccc tcg       96 
Arg Val Val Leu Pro Pro Asn Tyr Val Lys Glu Ile Arg Pro Pro Ser 
             20                  25                  30 

aag aag ggc tca cca gtg ata gta gac ttt agc ata ttc gtt gta gat      144 
Lys Lys Gly Ser Pro Val Ile Val Asp Phe Ser Ile Phe Val Val Asp 
         35                  40                  45 

att aac tca att aac gta gag gat atg gac ttt aga gta gac atg ttt      192 
Ile Asn Ser Ile Asn Val Glu Asp Met Asp Phe Arg Val Asp Met Phe 
     50                  55                  60 

ata cat cag cgc tgg ctg gag tcg cgt ctg gag atc cca gat gac ata      240 
Ile His Gln Arg Trp Leu Glu Ser Arg Leu Glu Ile Pro Asp Asp Ile 
 65                  70                  75                  80 

ttc gag gag ggc gac gac tac gtg acg ctg ctt cca gag gtc ttt gag      288 
Phe Glu Glu Gly Asp Asp Tyr Val Thr Leu Leu Pro Glu Val Phe Glu 
                 85                  90                  95 

aat ttt tgg cag ccg gat ccg tac ttt ctt aat tcc aaa att gcc gaa      336 
Asn Phe Trp Gln Pro Asp Pro Tyr Phe Leu Asn Ser Lys Ile Ala Glu 
            100                 105                 110 

ata gcg aca ctg acc cac aag ttc acg tcg gtg acg ctc tac aag aac      384 
Ile Ala Thr Leu Thr His Lys Phe Thr Ser Val Thr Leu Tyr Lys Asn 
        115                 120                 125 

aaa acg gtg cgc tat gcg gcc cgg atg cat gcg atc atc gcc tgc cag      432 
Lys Thr Val Arg Tyr Ala Ala Arg Met His Ala Ile Ile Ala Cys Gln 
    130                 135                 140 

atg gag ttc cag ctg tac ccc atg gac atc cag gtg tgt ccc atc tac      480 
Met Glu Phe Gln Leu Tyr Pro Met Asp Ile Gln Val Cys Pro Ile Tyr 
145                 150                 155                 160 

atc gag agc ttc tcg tcg aac aat caa aag gtt aag ctg cgc tgg tcc      528 
Ile Glu Ser Phe Ser Ser Asn Asn Gln Lys Val Lys Leu Arg Trp Ser 
                165                 170                 175 

gac tcc ggg gtg acc ctc aat ccg gaa ctg aag ctg ctg cag tac aat      576 
Asp Ser Gly Val Thr Leu Asn Pro Glu Leu Lys Leu Leu Gln Tyr Asn 
            180                 185                 190 

ctg ggc cag ccg ctg gaa ctg gag gag agc gac ggc tac atg ccg gag      624 
Leu Gly Gln Pro Leu Glu Leu Glu Glu Ser Asp Gly Tyr Met Pro Glu 
        195                 200                 205 

aag gtg ggg aac ttc tcc cgc ctc acc gta tac ttc cgc ttc gag cgc      672 
Lys Val Gly Asn Phe Ser Arg Leu Thr Val Tyr Phe Arg Phe Glu Arg 
    210                 215                 220 

cag att ggc cac cac ctc atc cag acc ttc gcc ccc tca tcg ctg gtg      720 
Gln Ile Gly His His Leu Ile Gln Thr Phe Ala Pro Ser Ser Leu Val 
225                 230                 235                 240 

ctt ctg gct ggg act gga cgc cat tcc ggg gcg cgt aac gct act ggt      768 
Leu Leu Ala Gly Thr Gly Arg His Ser Gly Ala Arg Asn Ala Thr Gly 
                245                 250                 255 

gac ctg cat gct gac cct ggt gac cat gtt acg ggc gcc gac att ccg      816 
Asp Leu His Ala Asp Pro Gly Asp His Val Thr Gly Ala Asp Ile Pro 
            260                 265                 270 

cca gtg gcc tac gtt aag gca ctg gat ctc tgg atg gcc ggg tgc atg      864 
Pro Val Ala Tyr Val Lys Ala Leu Asp Leu Trp Met Ala Gly Cys Met 
        275                 280                 285 

ctg tcc gtg ttc gcc gcg ctg gcc gag ttc gtg gtg gtg aaa gtg ctg      912 
Leu Ser Val Phe Ala Ala Leu Ala Glu Phe Val Val Val Lys Val Leu 
    290                 295                 300 

gac gtg cag tac cag tac cag gtg aac cgc ata ccc aag gta ctg ccc      960 
Asp Val Gln Tyr Gln Tyr Gln Val Asn Arg Ile Pro Lys Val Leu Pro 
305                 310                 315                 320 

atg cgc atc agc aat atg gag aag ggt cag tgt gcg acg gtg gcc agt     1008 
Met Arg Ile Ser Asn Met Glu Lys Gly Gln Cys Ala Thr Val Ala Ser 
                325                 330                 335 

tgg gag ggc gga gcg gtg cgg tcg cgg aag gcc act cag acg ccc acg     1056 
Trp Glu Gly Gly Ala Val Arg Ser Arg Lys Ala Thr Gln Thr Pro Thr 
            340                 345                 350 

aca ccg ggc cag ggt aac ggc gga ccg ccg aag cca gca aga cgt caa     1104 
Thr Pro Gly Gln Gly Asn Gly Gly Pro Pro Lys Pro Ala Arg Arg Gln 
        355                 360                 365 

agt cta ctt tcc gtg gcg tgg acg gat acg gat acc ggc gtg gag aag     1152 
Ser Leu Leu Ser Val Ala Trp Thr Asp Thr Asp Thr Gly Val Glu Lys 
    370                 375                 380 

atc atg tgg cga gag atc gac aag gtg tcc cgc gcc gta ttc ccc atc     1200 
Ile Met Trp Arg Glu Ile Asp Lys Val Ser Arg Ala Val Phe Pro Ile 
385                 390                 395                 400 

ctg ttc ttt gtg ttt gtg ctc ctg tac tgg ccg ata ctg ctg atg aag     1248 
Leu Phe Phe Val Phe Val Leu Leu Tyr Trp Pro Ile Leu Leu Met Lys 
                405                 410                 415 

tcg tcc tag                                                         1257 
Ser Ser 

 
           
             18  
             418  
             PRT  
             Drosophila melanogaster  
           
            18 

Met Leu Ser Glu Ala Thr Glu Ala His Met Asn Tyr Thr Ala Lys Pro 
  1               5                  10                  15 

Arg Val Val Leu Pro Pro Asn Tyr Val Lys Glu Ile Arg Pro Pro Ser 
             20                  25                  30 

Lys Lys Gly Ser Pro Val Ile Val Asp Phe Ser Ile Phe Val Val Asp 
         35                  40                  45 

Ile Asn Ser Ile Asn Val Glu Asp Met Asp Phe Arg Val Asp Met Phe 
     50                  55                  60 

Ile His Gln Arg Trp Leu Glu Ser Arg Leu Glu Ile Pro Asp Asp Ile 
 65                  70                  75                  80 

Phe Glu Glu Gly Asp Asp Tyr Val Thr Leu Leu Pro Glu Val Phe Glu 
                 85                  90                  95 

Asn Phe Trp Gln Pro Asp Pro Tyr Phe Leu Asn Ser Lys Ile Ala Glu 
            100                 105                 110 

Ile Ala Thr Leu Thr His Lys Phe Thr Ser Val Thr Leu Tyr Lys Asn 
        115                 120                 125 

Lys Thr Val Arg Tyr Ala Ala Arg Met His Ala Ile Ile Ala Cys Gln 
    130                 135                 140 

Met Glu Phe Gln Leu Tyr Pro Met Asp Ile Gln Val Cys Pro Ile Tyr 
145                 150                 155                 160 

Ile Glu Ser Phe Ser Ser Asn Asn Gln Lys Val Lys Leu Arg Trp Ser 
                165                 170                 175 

Asp Ser Gly Val Thr Leu Asn Pro Glu Leu Lys Leu Leu Gln Tyr Asn 
            180                 185                 190 

Leu Gly Gln Pro Leu Glu Leu Glu Glu Ser Asp Gly Tyr Met Pro Glu 
        195                 200                 205 

Lys Val Gly Asn Phe Ser Arg Leu Thr Val Tyr Phe Arg Phe Glu Arg 
    210                 215                 220 

Gln Ile Gly His His Leu Ile Gln Thr Phe Ala Pro Ser Ser Leu Val 
225                 230                 235                 240 

Leu Leu Ala Gly Thr Gly Arg His Ser Gly Ala Arg Asn Ala Thr Gly 
                245                 250                 255 

Asp Leu His Ala Asp Pro Gly Asp His Val Thr Gly Ala Asp Ile Pro 
            260                 265                 270 

Pro Val Ala Tyr Val Lys Ala Leu Asp Leu Trp Met Ala Gly Cys Met 
        275                 280                 285 

Leu Ser Val Phe Ala Ala Leu Ala Glu Phe Val Val Val Lys Val Leu 
    290                 295                 300 

Asp Val Gln Tyr Gln Tyr Gln Val Asn Arg Ile Pro Lys Val Leu Pro 
305                 310                 315                 320 

Met Arg Ile Ser Asn Met Glu Lys Gly Gln Cys Ala Thr Val Ala Ser 
                325                 330                 335 

Trp Glu Gly Gly Ala Val Arg Ser Arg Lys Ala Thr Gln Thr Pro Thr 
            340                 345                 350 

Thr Pro Gly Gln Gly Asn Gly Gly Pro Pro Lys Pro Ala Arg Arg Gln 
        355                 360                 365 

Ser Leu Leu Ser Val Ala Trp Thr Asp Thr Asp Thr Gly Val Glu Lys 
    370                 375                 380 

Ile Met Trp Arg Glu Ile Asp Lys Val Ser Arg Ala Val Phe Pro Ile 
385                 390                 395                 400 

Leu Phe Phe Val Phe Val Leu Leu Tyr Trp Pro Ile Leu Leu Met Lys 
                405                 410                 415 

Ser Ser