KR101819591B1 - biomarker comprising AGL gene in common associating aging, cancer and obesity and diagnosis kit using thereof - Google Patents

Abstract

The present invention relates to AGL (amylo-alpha-1,6-glucosidase, 4-alpha-glucanotransferase, CG9485) gene commonly associated with aging, obesity and cancer, and more specifically, .
The gene and diagnostic kit according to the present invention finds AGL (amylo-alpha-1,6-glucosidase, 4-alpha-glucanotransferase, CG9485) gene which is commonly involved in aging, obesity and cancer induction and development, And to provide a biomarker capable of analyzing progress of aging, obesity and cancer. Through this process, it is possible to comprehensively analyze or diagnose whether or not the progress of aging of mammals or insects other than humans and humans, cancer occurrence and obesity occurrence.

Description

Biomarkers comprising AGL genes commonly associated with aging, obesity and cancer, and biomarker comprising AGL gene in common associating aging, cancer and obesity and diagnosis kit uses thereof,

The present invention relates to AGL (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase, CG9485) gene commonly associated with aging, obesity and cancer, and more specifically relates to a diagnostic kit will be.

Studies on genes regulating senescence began in the early 1990s and are now actively under way. The genes regulating senescence so far have been classified into functional groups: catalase, superoxide dismutase, insulin / IGF-1 signaling pathway (including insulin, InR, PI3K, Akt and Foxo) (sirtuins), cancer suppression systems (p53, etc.), material delivery systems (sodium dicarboxylate cotransporter, etc.), and telomere control systems. These genes are closely involved in the regulation of senescence.

On the other hand, when aging progresses, cancer development also increases. Interestingly, cancer suppressor genes such as p53 regulate senescence at the same time. (Ras, Rac, Rap, Rala, Rhoa, etc.), Akt related genes (Akt / PKB, PKC, PKA, RAF, etc.) with serine / threonine kinase activity, , hedgehog-related genes, and protooncogene (c-Myc), and p53 and NFkB as cancer-suppressing genes. In particular, HGF and its receptor HGFR (c-met) are mainly associated with liver cancer. In addition, PTEN, a cancer-suppressing gene, inhibits the activity of PI3K. Overexpression of PTEN reduces the activity of the insulin / IGF-1 signal transduction system and increases its lifespan. In addition, all of these genes have been found in model organisms such as yeast, nematodes, Drosophila and mice, and research on human genes having functions to control cancer and aging in general has not been well studied yet.

Also, as aging progresses, obesity tends to occur. The causes of obesity related to aging include lack of exercise, growth hormone (GH) and hypothyroid hormone secretion. When the secretion of GH decreases, the metabolic effects of GH degrading carbohydrates, fats, Production is reduced and fat accumulation is induced. GH increases the secretion of IGF-1 in the liver, and thus, the decrease in GH secretion following aging will alter the activity of the insulin / IGF-1 signaling pathway and will be involved in the regulation of life span. For example, in the case of FIRKO mice in which insulin receptor is removed from adipocytes, fat accumulation may not occur even when overeating, and the body fat content of the fruit fly, an animal model of senescence, increases as aging proceeds . Therefore, despite the fact that obesity and aging are closely related, research on human genes that have the function of controlling aging and obesity in general is scarce.

In order to develop a biomarker, a diagnostic kit, a screening method, and the like that can discover genes that commonly control aging, cancer, and obesity, and can commonly diagnose aging, cancer, and obesity by confirming the expression of these genes There is a problem that the research is insufficient now.

On the other hand, Korean Patent Laid-Open Publication No. 10-2012-0021401 (Patent Document 1) has been disclosed as a prior art document related to the present invention, and Patent Document 1 discloses that the Atg5 gene is over- There is no disclosure or suggestion about a biomarker, a diagnostic kit and a screening method using a gene that commonly controls aging, cancer, and obesity, and the like, .

Patent Document 1. Korean Patent Laid-Open No. 10-2012-0021401

DISCLOSURE OF THE INVENTION The object of the present invention is to solve the above-mentioned problems, and it is an object of the present invention to provide a method for detecting a gene commonly involved in aging, cancer and obesity, And to provide a biomarker capable of quickly and accurately diagnosing cancer.

The present invention also provides a kit using the same and a method of discriminating or diagnosing the same.

In order to accomplish the above object, the present invention provides a recombinant DNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, And an mRNA thereof. The present invention also provides a biomarker for discriminating the progress of aging.

As the aging of the diagnostic subject is promoted, the expression amount of the biomarker is reduced.

In order to accomplish the above-mentioned other objects, the present invention provides a nucleotide sequence of any one selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, A nucleotide sequence, and a nucleotide sequence of any one of the nucleotide sequences and an mRNA thereof.

The amount of expression of the biomarker is decreased as the fat accumulation of the diagnostic subject is increased and the obesity is increased.

According to another aspect of the present invention, there is provided a recombinant DNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, And a base sequence of any one of the nucleotide sequence and mRNA thereof.

And the expression amount of the biomarker is decreased as the occurrence of cancer cells or cancer tissues of the diagnostic individual is increased.

According to another aspect of the present invention, there is provided a biomarker for determining aging progress. And a hybridization solution.

The biomarker may be present in a dispersed form in solution. And is present in the form of a microarray immobilized on a substrate.

According to another aspect of the present invention, there is provided a biomarker for obesity discrimination. And a hybridization solution.

The biomarker may be present in a dispersed form in solution. And is present in the form of a microarray immobilized on a substrate.

According to another aspect of the present invention, there is provided a biomarker for cancer diagnosis. And a hybridization solution.

The biomarker may be present in a dispersed form in solution. And is present in the form of a microarray immobilized on a substrate.

According to another aspect of the present invention, there is provided a biomarker comprising: And a hybridization solution; and a kit for complex diagnosis that simultaneously detects an aging process discrimination, an obesity discrimination, and a cancer diagnosis.

According to another aspect of the present invention, there is provided an aging process discriminating method comprising the steps of:

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or cDNA synthesized therefrom with the aging-progression-determining kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

According to another aspect of the present invention, there is provided an obesity discrimination method comprising the steps of:

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or the synthesized cDNA with the obesity-determining kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

According to another aspect of the present invention, there is provided a cancer diagnosis method comprising the steps of:

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or the synthesized cDNA with the cancer diagnostic kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

According to another aspect of the present invention, there is provided a method for detecting progression of aging, discrimination of increase in obesity, and cancer diagnosis including the following steps.

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or cDNA synthesized therefrom with the complex diagnostic kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

The gene and diagnostic kit according to the present invention finds AGL (amylo-alpha-1,6-glucosidase, 4-alpha-glucanotransferase, CG9485) gene which is commonly involved in aging, obesity and cancer induction and development, Thereby enabling the analysis of aging progress, obesity and cancer. Thus, it is possible to comprehensively analyze or diagnose whether progress of human aging, cancer occurrence, and obesity has occurred.

Figure 1 is a graph showing Actin-GS-Gal4 / + W1118 lifetime curves for RU486 treatment.
FIG. 2 shows the results of decreasing the amount of AGL mRNA when AGL expression was inhibited using Actin-GS-Gal4 and UAS-AGL RNAi.
FIG. 3 is a graph showing the results of confirming that the lifespan is shortened when the expression of AGL is decreased.
FIG. 4 shows the change in the triglyceride content of wild-type fruit fly fed with RU486.
FIG. 5 shows the results of the addition of Actin-GS-Gal4 / +; UAS-AGL RNAi / + Drosophila.
Fig. 6 is a confocal microscopic photograph of the fat body tissue of Actin-GS-Gal4 / UAS-nls. GFP fruit flies fed with RU486.
FIG. 7 is a photograph of a confocal microscope taken after Nil red staining of fat of fat tissue of Actin-GS-Gal4 / UAS-AGL RNAi fruit fly fed with RU486.
8 shows the results of comparison of the blade lengths of cancer growth model flies (UAS-PI3K; c765-Gal4) and cancer-proliferation model flies (UAS-Ras85D; c765-Gal4).
FIG. 9 is a result of comparison of the blade lengths of cancer growth model flies (UAS-PI3K / +; c765-Gal4 / UAS-AGL RNAi) inhibiting AGL gene expression.
Fig. 10 shows the results of comparison of wing areas of cancer growth model flies (UAS-PI3K / +; c765-Gal4 / UAS-AGL RNAi) inhibiting AGL gene expression.
11 is a comparison of the wing length of cancer growth model flies (UAS-Ras85D / +; c765-Gal4 / UAS-AGL RNAi) inhibiting AGL gene expression.
12 is a comparison of the wing area of cancer growth model flies (UAS-Ras85D / +; c765-Gal4 / UAS-AGL RNAi) inhibiting AGL gene expression.

Therefore, the present inventors have made intensive efforts to discover genes commonly involved in aging, obesity and cancer. As a result, it has been found that amylo-alpha-1,6-glucosidase (AGL), which is commonly involved in aging, obesity, 4-alpha-glucanotransferase, CG9485) gene.

Hereinafter, the present invention will be described in more detail.

It is an object of the present invention to provide a biomarker capable of promptly and simply discriminating the progress of aging of a mammal or an insect other than human or human.

One aspect of the present invention is a nucleotide sequence of any one selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, And a biomarker for determining the progress of aging comprising at least one base sequence selected from the group consisting of SEQ ID NOs.

A gene consisting of any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, The expression level decreases as aging, which is a phenotype of the life span of the diagnostic individual, is promoted.

Thus, using this characteristic, the nucleotide sequence is a biomarker capable of discriminating the progress of aging by comparing the standard amount of the nucleotide sequence in the same species as that of the diagnostic individual and the expression amount of the nucleotide sequence in the diagnostic individual Can be utilized.

In this specification, a biomarker for determining the progress of aging means a biomarker capable of qualitatively discriminating the life span, that is, the progress of aging.

As described above, the mammalian animals or insects except humans or humans according to the present invention have genetic differences with each other, and the average degree of progression of aging is completely different. However, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences and their mRNA The present invention provides a biomarker for determining the progress of aging, whereby the progress of aging of a diagnostic object can be quickly, accurately, and simply determined for each species.

Any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 is usually UAS 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 5 as long as they are extracted from a Drosophila mutant that controls the expression of a specific gene by the GAL4 system. The nucleotide sequence of SEQ ID NO: 6 is the amylo-alpha-1,6-glucosidase, 4-alpha-glucanotransferase (CG9485) gene of Drosophila.

In the present invention, GAL / UAS expression system was used for evaluating the function of candidate genes using Drosophila. Specifically, a Gene Switch (GS) GAL / UAS expression system was used. GAL4 was originally a yeast protein. GAL4, which is expressed by introducing it into Drosophila, binds to a DNA sequence called Upstream Activating Sequencers (UAS) when a drug called RU486 (mifepristone) is present and activates the transcription of a specific gene after UAS , And transcription of a specific gene is inactivated if RU486 is not present. Using this, AGL RNAi activity was regulated to control AGL gene expression and its function was confirmed.

A nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, a complementary base sequence thereof, Specific nucleotide sequence promotes senescence of Drosophila when expression is specifically reduced.

Specifically, after the expression of the gene of the UAS-GAL4 gene has been exposed to RU486, the effect of decreasing the expression of the specific gene by more than 2-fold was confirmed through repeated experiments. As a result, From any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, When the expression of the gene containing at least one selected nucleotide sequence is decreased more than 2 times, it has been confirmed that the senescence further progresses. As a result, the above-mentioned gene is a biomarker for discriminating the aging of a mammal or an insect, .

Furthermore, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, (Homologue) with the gene of ADHFE1 (alcohol dehydrogenase, iron containing, 1, NP_653251.2 467 aa) of human, it is possible to use the biomarker according to the present invention as an insect It is also possible to determine whether a person is aging or not.

Any one selected from the group consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, The above base sequence is a cDNA having no intron, and the cDNA is prepared by complementary DNA using mRNA produced by transcription from genomic DNA.

That is, when the biomarker is used, the progress of aging of mammals and insects other than humans and humans can be discriminated, and thus it is expected to be useful for discriminating and responding to the progress of aging of diagnostic objects.

It is an object of the present invention to provide a biomarker capable of promptly and simply discriminating obesity of a mammal or an insect other than human or human.

One aspect of the present invention is a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, mRNA, which comprises at least one nucleotide sequence selected from the group consisting of:

A gene consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, The nucleotide sequence of any one selected from the group consisting of these mRNAs decreases in expression level as the diagnostic individual is obese (specifically, the content of triglycerides increases and the size and density of lipids in fat tissue increase).

Therefore, using the above characteristics, the nucleotide sequence can be used as a biomarker capable of discriminating the increase in obesity by comparing the standard amount of the nucleotide sequence of the same species as that of the diagnostic individual with the expression amount of the nucleotide sequence measured in the diagnostic individual .

In this specification, biomarker for discrimination of obesity means a biomarker capable of qualitatively discriminating the increase in obesity (specifically, increase in triglyceride content and increase in size and density of fat globule in fat body tissue).

As described above, since mammals or insects other than humans or humans according to the present invention have genetic differences with each other, there will be a difference in obesity. However, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences and their mRNA Can be used as a biomarker for discriminating obesity, whereby it is possible to quickly, accurately, and simply determine the obesity of a diagnostic individual for each species.

Any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 ordinarily controls the expression of a specific gene by the UAS-GAL4 system But is not limited to, any one selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 The nucleotide sequence is the AGL (amylo-alpha-1,6-glucosidase, 4-alpha-glucanotransferase, CG9485) gene of Drosophila.

In the present invention, GAL / UAS expression system was used for evaluating the function of candidate genes using Drosophila. Specifically, a Gene Switch (GS) GAL / UAS expression system was used. GAL4 was originally a yeast protein. GAL4, which is expressed by introducing it into Drosophila, binds to a DNA sequence called Upstream Activating Sequencers (UAS) when a drug called RU486 (mifepristone) is present and activates the transcription of a specific gene after UAS , And transcription of a specific gene is inactivated if RU486 is not present. Using this, AGL RNAi activity was regulated to control AGL gene expression and its function was confirmed.

From any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, One or more of the selected base sequences is specifically reduced in expression as the triglyceride content of Drosophila and the size and density of lipids in fat tissue are greatly increased.

Specifically, after the expression of the gene of the UAS-GAL4 gene has been exposed to RU486, the effect of decreasing the expression of the specific gene by more than 2-fold was confirmed through repeated experiments. As a result, From any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, It was confirmed that obesity increases when the expression of a gene comprising at least one selected nucleotide sequence is reduced by a factor of two or more. As a result, the above-mentioned gene is a biomarker for determining the obesity of a mammal or an insect, Can be used.

Furthermore, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, (Homologue) with the gene of ADHFE1 (alcohol dehydrogenase, iron containing, 1, NP_653251.2 467 aa) of human, it is possible to use the biomarker according to the present invention as an insect It can also determine whether a person is obese.

Any one selected from the group consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, The above base sequence is a cDNA having no intron, and the cDNA is prepared by complementary DNA using mRNA produced by transcription from genomic DNA.

That is, when the biomarker is used, it is possible to discriminate the triglyceride contents of mammals and insects other than humans and humans, and the size and density of lipids in fat body tissues. .

It is an object of the present invention to provide a biomarker capable of rapidly and simply diagnosing cancer of a mammal or an insect other than human or human.

One aspect of the present invention is a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, mRNA. The present invention also relates to a biomarker for cancer diagnosis comprising at least one base sequence selected from the group consisting of mRNAs.

A gene consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, a complementary base sequence thereof, , The expression level decreases as the cancer occurrence or proliferation (specifically, the phenotype of the cancer growth model Drosophila) increases in the diagnostic individual.

Therefore, by using such a characteristic, the nucleotide sequence can be determined by comparing the standard onset amount of the base sequence in the same species as the diagnostic individual and the expression amount of the determined base sequence in the diagnostic individual to determine a biomarker .

In the present specification, biomarker for cancer diagnosis means a biomarker capable of qualitatively discriminating whether cancer cells and tissues proliferate or grow.

As described above, since the mammalian animal or insect except the human or human according to the present invention has a genetic difference with each other, the occurrence of cancer is completely different. However, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences and their mRNA Can be used as a cancer diagnostic diagnostic biomarker, it is possible to promptly, accurately, and simply determine the cancer occurrence or growth of a diagnostic individual for each species.

Any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 ordinarily controls the expression of a specific gene by the UAS-GAL4 system Preferably, the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 is selected from the group consisting of AGL -alpha-1,6-glucosidase, 4-alpha-glucanotransferase, CG9485) gene.

In the present invention, GAL / UAS expression system was used for evaluating the function of candidate genes using Drosophila. Specifically, a Gene Switch (GS) GAL / UAS expression system was used. GAL4 was originally a yeast protein. GAL4, which is expressed by introducing it into Drosophila, binds to a DNA sequence called Upstream Activating Sequencers (UAS) when a drug called RU486 (mifepristone) is present and activates the transcription of a specific gene after UAS , And transcription of a specific gene is inactivated if RU486 is not present. Using this, AGL RNAi activity was regulated to control AGL gene expression and its function was confirmed.

From the group consisting of any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, One or more of the selected base sequences is specifically reduced in expression as the triglyceride content of Drosophila and the size and density of lipids in fat tissue are greatly increased.

Specifically, the effect of the expression of a specific gene on the expression of RU486 after the expression of a specific gene was controlled by the UAS-GAL4 system was more than twice as much as that of the wild-type mutant (SEQ ID NO: 1), SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6 , Complementary nucleotide sequences thereof, and mRNAs thereof, the expression of the gene comprising the nucleotide sequence of SEQ ID NO: 1, 2, Or as a biomarker for diagnosing the occurrence of cancer in a mammal or an insect other than a human.

Furthermore, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, (Homologue) with the gene of ADHFE1 (alcohol dehydrogenase, iron containing, 1, NP_653251.2 467 aa) of human, it is possible to use the biomarker according to the present invention as an insect It is also possible to diagnose whether a person has cancer or proliferation.

Any one selected from the group consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, The above base sequence is a cDNA having no intron, and the cDNA is prepared by complementary DNA using mRNA produced by transcription from genomic DNA.

That is, when the biomarker is used, it is possible to determine whether the mammals and insects except humans and humans are able to generate and proliferate cancer, and thus it is expected to be useful for diagnosing and responding to cancer of each diagnostic object.

In addition, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, mRNA, can detect aging discrimination, obesity discrimination, and cancer diagnosis as described above. At the same time, the biomarker including any one or more of the nucleotide sequences selected from the group consisting of mRNAs can detect aging progress, obesity increase, .

As described above, any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, their complementary base sequences, , The aging of the fruit fly mutant which reduces the expression of a specific gene is further promoted by using the UAS-GAl4 system, and the fat purity of the triglyceride and lipid body tissues is increased, Based on the increase in size and the decrease in cancer incidence, the standard outbreak of biomarker in the same species as the diagnostic individual and the measured biomarker expression level in the diagnostic individual were compared to find out whether progress of aging, Can be detected at the same time.

In the present invention, the biomarker may be any one selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, As well as the mRNA of the base sequence. The protein may be any one or more of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12.

The protein represented by any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 may also be used as an agonist, Cancer can be distinguished and diagnosed.

The kit using the protein may include a kit for ELISA (Enzyme linked immunosorbent assay), and the antibody specifically binding to the protein may be administered to a biological sample selected from a cell, tissue, urine, blood, serum, Through the step of contacting the sample, the antigen-antibody complex can be quantitatively detected.

The detection result may be compared with a standard protein expression amount in a diagnostic subject to discriminate and diagnose any one or more selected from aging, obesity and cancer of the diagnostic subject.

Analysis methods for measuring protein expression include Western blotting, enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, , Immunoprecipitation, Complement fixation assay, FACS, Protein chip, etc., and are not limited to the described methods.

Through the above analysis method, it is possible to compare the amount of the standard antigen-antibody complex formed in the same species as the diagnostic individual with the amount of the antigen-antibody complex formed in the diagnostic individual, and the significant expression level of the protein expressed by the amino acid sequence 2 , It is possible to discriminate or diagnose any one or more of aging progression, obesity increase, and cancer development.

Another aspect of the present invention relates to a kit for determining the progress of aging comprising the biomarker and the hybridization solution.

The biomarker is as described above, and may be stored in a solution, or the biomarker may be immobilized on the substrate at a high density. In other words, the biomarkers may be in a microarray form immobilized in a predetermined region. Such microarrays are well known in the art.

The kit may be dispersed in a solution or hybridized with the biomarker immobilized on the substrate and mRNA or cDNA extracted from a diagnostic object to confirm whether mRNA or cDNA of the same sequence is expressed.

Therefore, a biomarker used in the kit requires a process of removing one strand from its base sequence.

Refers to any substrate to which the biomarker can be coupled under conditions where the substrate retains the hybridization property and the background level of hybridization is kept low when the biomarker is in the form of a microarray immobilized on a substrate. Typically, the substrate can be a microtiter plate, a membrane (e.g., nylon or nitrocellulose) or a microsphere (bead) or chip.

Before application or fixation to the membrane, the biomarker may be modified to immobilize or improve the hybridization efficiency. Such modifications may include coupling with different reactive functional groups such as homopolymer tailings, aliphatic groups, NH2 groups, SH groups and carboxyl groups, or coupling with biotin, haptens or proteins.

"Hybridization" means a process in which two complementary strands of a nucleic acid are combined to form a double stranded molecule (hybrid).

The hybridization solution is a buffer solution that allows hybridization of the biomarker and the mRNA or cDNA extracted from the diagnostic object, and a solution known in the art can be used.

The kit may further include a detector capable of detecting a nucleic acid of a diagnostic object hybridized with the biomarker. The detector may be a scanner, a spectrophotometer, a liquid scintillation counter, or the like, but is not limited thereto. The kit of the present invention may further include a user's manual describing optimal reaction performance conditions.

The kit can qualitatively detect the progress of aging by comparing the standard outbreak amount of the biomarker in the same species as the diagnostic subject and the measured biomarker expression amount in the diagnostic subject. Specifically, Of the biomarker of the present invention and the amount of expression of the biomarker measured in the diagnostic individual are compared with each other, it is accurately determined that the amount of expression in the diagnostic subject is decreased, It can be quickly identified.

Another aspect of the present invention relates to an obesity-determining kit comprising the biomarker and the hybridization solution.

The biomarker is as described above, and may be stored in a solution, or the biomarker may be immobilized on the substrate at a high density. In other words, the biomarkers may be in a microarray form immobilized in a predetermined region. Such microarrays are well known in the art.

The kit may be dispersed in a solution or hybridized with the biomarker immobilized on the substrate and mRNA or cDNA extracted from a diagnostic object to confirm whether mRNA or cDNA of the same sequence is expressed.

Therefore, a biomarker used in the kit requires a process of removing one strand from its base sequence.

Refers to any substrate to which the biomarker can be coupled under conditions where the substrate retains the hybridization property and the background level of hybridization is kept low when the biomarker is in the form of a microarray immobilized on a substrate. Typically, the substrate can be a microtiter plate, a membrane (e.g., nylon or nitrocellulose) or a microsphere (bead) or chip.

Before application or fixation to the membrane, the biomarker may be modified to immobilize or improve the hybridization efficiency. Such modifications may include coupling with different reactive functional groups such as homopolymer tailings, aliphatic groups, NH2 groups, SH groups and carboxyl groups, or coupling with biotin, haptens or proteins.

"Hybridization" means a process in which two complementary strands of a nucleic acid are combined to form a double stranded molecule (hybrid).

The hybridization solution is a buffer solution that allows hybridization of the biomarker and the mRNA or cDNA extracted from the diagnostic object, and a solution known in the art can be used.

The kit may further include a detector capable of detecting a nucleic acid of a diagnostic object hybridized with the biomarker. The detector may be a scanner, a spectrophotometer, a liquid scintillation counter, or the like, but is not limited thereto. The kit of the present invention may further include a user's manual describing optimal reaction performance conditions.

The kit can qualitatively detect the degree of obesity by comparing the standard amount of biomarker of the same species as the diagnostic individual and the measured biomarker expression amount in the diagnostic individual. Specifically, When the expression level of the biomarker is compared with the standard expression level of the biomarker and the expression level of the biomarker measured in the diagnostic subject, if the expression level in the diagnostic subject is decreased, the diagnostic subject has a higher average triglyceride content and liposome size and density State can be accurately and quickly determined.

Another aspect of the present invention relates to a cancer diagnostic kit comprising the biomarker and the hybridization solution.

The biomarker is as described above, and may be stored in a solution, or the biomarker may be immobilized on the substrate at a high density. In other words, the biomarkers may be in a microarray form immobilized in a predetermined region. Such microarrays are well known in the art.

The kit may be dispersed in a solution or hybridized with the biomarker immobilized on the substrate and mRNA or cDNA extracted from a diagnostic object to confirm whether mRNA or cDNA of the same sequence is expressed.

Therefore, a biomarker used in the kit requires a process of removing one strand from its base sequence.

Refers to any substrate to which the biomarker can be coupled under conditions where the substrate retains the hybridization property and the background level of hybridization is kept low when the biomarker is in the form of a microarray immobilized on a substrate. Typically, the substrate can be a microtiter plate, a membrane (e.g., nylon or nitrocellulose) or a microsphere (bead) or chip.

Before application or fixation to the membrane, the biomarker may be modified to immobilize or improve the hybridization efficiency. Such modifications may include coupling with different reactive functional groups such as homopolymer tailings, aliphatic groups, NH2 groups, SH groups and carboxyl groups, or coupling with biotin, haptens or proteins.

"Hybridization" means a process in which two complementary strands of a nucleic acid are combined to form a double stranded molecule (hybrid).

The hybridization solution is a buffer solution that allows hybridization of the biomarker and the mRNA or cDNA extracted from the diagnostic object, and a solution known in the art can be used.

The kit may further include a detector capable of detecting a nucleic acid of a diagnostic object hybridized with the biomarker. The detector may be a scanner, a spectrophotometer, a liquid scintillation counter, or the like, but is not limited thereto. The kit of the present invention may further include a user's manual describing optimal reaction performance conditions.

The kit can qualitatively detect the degree of obesity by comparing the standard amount of biomarker of the same species as the diagnostic individual and the measured biomarker expression amount in the diagnostic individual. Specifically, When the standard expression level of the biomarker is compared with the expression level of the biomarker measured in the diagnostic subject, if the expression level in the diagnostic subject is decreased, the diagnostic subject can accurately and promptly show that the cancer develops or grows Can be diagnosed.

In addition, the kit according to the present invention can be used for aging discrimination, obesity discrimination and cancer diagnosis as described above, but can also be used as a complex diagnosis kit for simultaneously detecting aging progress, obesity increase, and cancer occurrence.

As described above, the complex diagnostic kit may comprise any one of the nucleotide sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, And a hybridization solution containing at least one of the nucleotide sequences selected from the group consisting of mRNAs of the genes and the hybridization solution of the biomarkers, wherein the expression of the biomarkers is decreased, Based on the progressive aging of the mutant, the increase in lipid density and size in triglyceride and lipid body tissues, and the reduction in cancer incidence, the standard biomarker biomarker and diagnostic The amount of biomarker expressed in the individual was compared to determine whether progression of aging, increase in obesity, And can be used as a complex diagnostic kit.

Another aspect of the present invention relates to a method of determining aging progress comprising the following steps.

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or cDNA synthesized therefrom with the aging-progression-determining kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

A method known in the art can be used as a method for separating RNA from the diagnostic entity. Specifically, it may be a step of isolating RNA from the cells of the separated diagnostic subject in vitro using cells separated from the diagnostic subject.

According to an embodiment of the present invention, the cDNA may be a first strand cDNA synthesized using the separated RNA as a template. The first strand cDNA can be synthesized by a method commonly used in the art, for example, a reverse transcriptase, an RNase block ribonuclease inhibitor, or the like. Examples of reverse transcriptase enzymes include, but are not limited to, reverse transcriptase from a variety of sources such as avian myeloblastosis virus-derived virus reverse transcriptase (AMV RTase), mouse leukemia virus-derived reverse transcriptase murine leukemia virus-derived virus reverse transcriptase (MMLV RTase) and Rous-associated virus 2 reverse transcriptase (RAV-2 RTase).

Preferably, the cDNA can be labeled with a detectable labeling substance. The labeling substance may be a fluorescent, phosphorescent or radioactive substance, but is not limited thereto. Preferably, the labeling substance is Cy5 or Cy3. When the first strand cDNA is synthesized by labeling Cy5 or Cy3 at the 5'-end of the primer, the target sequence may be labeled with a detectable fluorescent labeling substance. When the radioactive isotope such as ³² P or ³⁵ S is added to the reaction solution during the synthesis of the first strand cDNA, the synthesis product is synthesized and the radioactive is incorporated into the synthesis product and the synthesis product is labeled with radioactivity have.

The step of detecting the degree of hybridization may be performed through capillary electrophoresis, gel electrophoresis, radioactivity measurement, fluorescence measurement or phosphorescence measurement.

According to another embodiment of the present invention, the aging progress discrimination method may further include a step of comparing aging progress of the diagnostic subject by comparing the detection result with the standard of the diagnostic subject.

On the other hand, the aging progression discrimination method is for providing information necessary for discriminating the aging progress of the diagnostic subject, separating RNA from the cells of the separated diagnostic subject in vitro using the cells isolated from the diagnostic subject, A probe capable of detecting the expression of any one of the nucleotide sequences selected from the group consisting of SEQ ID NOS: 1 to 6 or the expression of any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 1 to 6 or a protein comprising any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 is detected by adding an antibody having the amino acid sequence of SEQ ID NO: .

The method may further include comparing the detected expression level of the gene and protein with the standard of the diagnostic subject to determine whether or not the diagnostic subject is progressing to aging.

The diagnostic object may be a mammal or an insect other than human or human.

Another aspect of the present invention relates to an obesity discrimination method comprising the following steps.

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or the synthesized cDNA with the obesity-determining kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

A method known in the art can be used as a method for separating RNA from the diagnostic entity.

Specifically, it may be a step of isolating RNA from the cells of the separated diagnostic subject in vitro using cells separated from the diagnostic subject.

According to an embodiment of the present invention, the cDNA may be a first strand cDNA synthesized using the separated RNA as a template. The first strand cDNA can be synthesized by a method commonly used in the art, for example, a reverse transcriptase, an RNase block ribonuclease inhibitor, or the like. Examples of reverse transcriptase enzymes include, but are not limited to, reverse transcriptase from a variety of sources such as avian myeloblastosis virus-derived virus reverse transcriptase (AMV RTase), mouse leukemia virus-derived reverse transcriptase murine leukemia virus-derived virus reverse transcriptase (MMLV RTase) and Rous-associated virus 2 reverse transcriptase (RAV-2 RTase).

Preferably, the cDNA can be labeled with a detectable labeling substance. The labeling substance may be a fluorescent, phosphorescent or radioactive substance, but is not limited thereto. Preferably, the labeling substance is Cy5 or Cy3. When the first strand cDNA is synthesized by labeling Cy5 or Cy3 at the 5'-end of the primer, the target sequence may be labeled with a detectable fluorescent labeling substance. When the radioactive isotope such as ³² P or ³⁵ S is added to the reaction solution during the synthesis of the first strand cDNA, the synthesis product is synthesized and the radioactive is incorporated into the synthesis product and the synthesis product is labeled with radioactivity have.

The step of detecting the degree of hybridization may be performed through capillary electrophoresis, gel electrophoresis, radioactivity measurement, fluorescence measurement or phosphorescence measurement.

According to another embodiment of the present invention, the above-mentioned method of discriminating obesity comprises comparing the detection result with the standard of the diagnostic object, thereby determining an increase in the triglyceride content of the diagnostic subject, Based on the result of the determination.

On the other hand, the above-mentioned obesity discrimination method is for providing information necessary for discrimination of obesity of the diagnosis object, and separating RNA from the cells of the separated diagnosis subject in vitro using the cells isolated from the diagnosis subject, A probe capable of detecting the expression of any one of the nucleotide sequences selected from the group consisting of SEQ ID NOS: 1 to 6 or an antibody capable of detecting the expression of any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 1 to 6 or a protein comprising any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 by the addition of the nucleotide sequence of SEQ ID NO: .

The step of comparing the detected gene and protein expression level with the standard of the diagnostic subject to determine whether the diagnostic subject is obese (increase in the triglyceride content and increase in the size and density of the fat sphere in the fat body tissue) .

The diagnostic object may be a mammal or an insect other than human or human.

Another aspect of the invention relates to a method of diagnosing cancer comprising the steps of:

I) isolating and extracting RNA from a diagnostic individual;

II) contacting the isolated RNA or the synthesized cDNA with the cancer diagnostic kit to hybridize the RNA or cDNA with the biomarker; And

III) detecting the degree of hybridization between the biomarker and the RNA or cDNA.

A method known in the art can be used as a method for separating RNA from the diagnostic entity. Specifically, it may be a step of isolating RNA from the cells of the separated diagnostic subject in vitro using cells separated from the diagnostic subject.

According to an embodiment of the present invention, the cDNA may be a first strand cDNA synthesized using the separated RNA as a template. The first strand cDNA can be synthesized by a method commonly used in the art, for example, a reverse transcriptase, an RNase block ribonuclease inhibitor, or the like. Examples of reverse transcriptase enzymes include, but are not limited to, reverse transcriptase from a variety of sources such as avian myeloblastosis virus-derived virus reverse transcriptase (AMV RTase), mouse leukemia virus-derived reverse transcriptase murine leukemia virus-derived virus reverse transcriptase (MMLV RTase) and Rous-associated virus 2 reverse transcriptase (RAV-2 RTase).

Preferably, the cDNA can be labeled with a detectable labeling substance. The labeling substance may be a fluorescent, phosphorescent or radioactive substance, but is not limited thereto. Preferably, the labeling substance is Cy5 or Cy3. When the first strand cDNA is synthesized by labeling Cy5 or Cy3 at the 5'-end of the primer, the target sequence may be labeled with a detectable fluorescent labeling substance. When the radioactive isotope such as ³² P or ³⁵ S is added to the reaction solution during the synthesis of the first strand cDNA, the synthesis product is synthesized and the radioactive is incorporated into the synthesis product and the synthesis product is labeled with radioactivity have.

The step of detecting the degree of hybridization may be performed through capillary electrophoresis, gel electrophoresis, radioactivity measurement, fluorescence measurement or phosphorescence measurement.

According to another embodiment of the present invention, the cancer diagnosis method may further include a step of comparing the detection result with the standard of the diagnostic object to diagnose cancer through the cancer occurrence or growth of the diagnostic object.

On the other hand, the cancer diagnosis method is for providing information necessary for cancer diagnosis of the diagnostic individual, separating RNA from the cells of the separated diagnostic individual in vitro using the cells isolated from the diagnostic individual, A probe capable of detecting the expression of any one of the nucleotide sequences selected from the group consisting of SEQ ID NOS: 1 to 6 or an antibody capable of detecting the expression of any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 1 to 6 or a protein comprising any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 7 to 12 by the addition of the nucleotide sequence of SEQ ID NO: .

The method may further include the step of diagnosing cancer occurrence and growth of the diagnostic subject by comparing the detected gene and protein expression level with the standard of the diagnostic subject.

The diagnostic object may be a mammal or an insect other than human or human.

In the present invention, it is possible to simultaneously detect progress of aging, increase in obesity, and whether or not cancer has occurred by using the above-described multiple diagnosis kit according to the present invention. It is possible.

As described above, the complex diagnosis kit is performed in the same manner as the determination method using each of the above-described kits.

However, the detection result can be compared with the standard of the diagnostic subject to determine whether the diagnosis subject is aged, obese, cancerous, or growing.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

Example

<Preparation process>

In order to investigate the progression of aging, we first examined whether Actin-GS-Gal4 Drosophila and wild-type (w1118) Drosophila were crossed to affect the lifespan of RU486. As a result, RU486 did not affect the lifespan (See Figure 1 below).

Actin-GS-Gal4 is expressed in Drosophila when RU486 is present. UAS-AGL RNAi is reduced in expression of AGL due to RNAi action of AGL when Gal4 is produced. The amount of AGL mRNA was detected by RT-PCR in order to determine whether expression of AGL was decreased in the offspring (F1) fruit fly obtained by crossing Actin-GS-Gal4 with UAS-AGL RNAi Drosophila. The amount of AGL mRNA Was significantly reduced compared to when it did not feed RU486. This result demonstrates that Actin-GS-Gal4 and UAS-AGL RNAi are functioning normally (see FIG. 2 below).

[Example 1: Actin-GS-Gal4> RT-PCR of UAS-AGL RNAi]

To confirm that UAS-AGL RNAi Drosophila is working properly, Actin-GS-Gal4 Drosophila females and UAS-AGL RNAi Drosophila males were mated to collect F1 males of F1 generation and cultured in media containing RU486 (150 μM) Alpha-1, 6-glucosidase, 4 (AGL) was grown for 10 days on medium without agar, 0.7% agar, 6.1% corn flour, 2.6% yeast, 1.6% Tegosept and 80.7% -alpha-glucanotransferase, CG9485) was performed by reverse transcriptase-mediated PCR (RT-PCR). As a result, it was confirmed that UAS-AGL RNAi was activated and the amount of AGL mRNA of cultured fruit flies was significantly decreased in the medium containing RU486 compared with the control.

[Example 2: Lifetime measurement of Actin-GS-Gal4 > UAS-AGL RNAi Drosophila fed RU486]

Actin-GS-Gal4 Drosophila females and UAS-AGL RNAi Drosophila males were mated to collect males of F1 generation, and 120 rats were placed in a medium containing RU486 (150 μM) and RU486-free medium. The lifespan was measured while growing at 25 ° C, 50% relative humidity, and 12:12 hour light cycle. The experiment measuring the lifetime was repeated three times. As shown in the results of FIG. 3, it can be seen that when the expression of AGL is decreased, the life span decreases, that is, aging progresses further (see FIG. 3).

[Example 3: Actin-GS-Gal4 fed with RU486] Measurement of Neutral Fat in UAS-AGL RNAi Drosophila]

Actin-GS-Gal4 Drosophila females and UAS-AGL RNAi Drosophila males were mated to collect males of F1 generation and grown for about 10 days in a medium containing RU486 (150 μM) and a medium containing no RU486 The neutral fat was measured using thin layer chromatography (TLC) (see FIG. 4 below as a result of measurement of the change in the triglyceride content of wild type Drosophila fed with RU486). 10 μl of Drosophila was placed in an Eppendorf tube, and 100 μl of an extraction solvent (10 mM Tris, 1 mM EDTA, 0.1% TritonX-100) was added for 5 minutes and centrifuged. 5 μl of the supernatant was subjected to TLC And then dropped on a plate. TLC eluting solvent composition for the separation of triglyceride was hexane; diethylether; acetic acid (70: 30: 1) and sesame oil (Sigma-Aldrich S3547-250ML). After developing on the TLC plate, the TLC plate was dried, placed in an iodine saturation box, stained with TLC plates, pictures were taken, and neutral fat bands were quantified using the Image J program. As a result, it was confirmed that the triglyceride content in RU486-fed Drosophila, that is, the group in which AGL expression was inhibited, was significantly increased (see FIG. 5).

[Example 4: Actin-GS-Gal4 fed with RU486] Analysis of liposome confocal microscope of UAS-AGL RNAi fruit flies [

In order to observe lipid size, Actin-GS-Gal4 Drosophila females and UAS-AGL RNAi Drosophila males were mated to collect males of F1 generation and cultured for 10 days in media containing RU486 (150 μM) and RU486 And dyed with Nile red. Drosophila was dissected and fixed in 4% paraformaldehyde solution dissolved in PBS for 30 minutes at room temperature. After washing with PBS, 0.5 mg / ml Nile red (Sigma) solution was diluted 1: 2,500 and incubated at room temperature for 30 minutes After staining, wash with distilled water twice. The dyed samples were then placed in a 80% glycerol solution on a slide glass and measured by a confocal microscope (see FIG. 6, below). Actin-GS-Gal4 / UAS-nls. GFP fed with RU486 Focus confocal microscope photo). As a result, it was confirmed that the size and density of lipids were increased (see FIG. 7).

Example 5: Production of cancer growth model flies (UAS-PI3K; c765-Gal4)

In order to carry out a study on cancer, c765-Gal4 Drosophila and UAS-PI3K Drosophila were crossed to produce cancer growth model flies.

[Example 6: preparation of cancer proliferation model fruit fly (UAS-Ras85D; c765-Gal4)] [

In order to carry out a study on cancer, the cancer growth model flies were prepared by crossing c765-Gal4 Drosophila and UAS-Ras85D Drosophila.

[Example 7: phenotypic analysis of cancer growth model flies (UAS-PI3K; c765-Gal4)

Fabricated UAS-PI3K; C765-Gal4 / + CS10, UAS-PI3K / + CS10 and UAS-PI3K / + CS10 crossing wild-type flies (CS10) with c765-Gal4 and CS10 to analyze the phenotype of the c765-Gal4 cancer proliferation blackfly flies model. The wing length of c765-Gal4 / + CS10 was compared with UAS-PI3K / + CS10; The wing length of c765-Gal4 / + CS10 was longer than that of the three control groups. The wing length was compared with the length of the chest to compensate for the difference between the individual flies. That is, cancer proliferation assay model (see FIG. 8 below).

[Example 8: phenotypic analysis of cancer proliferation model fruit fly (UAS-Ras85D; c765-Gal4)] [

Manufactured UAS-Ras85D; C765-Gal4 / + CS10, UAS-Ras85D / + CS10 and UAS-Ras85D / + CS10 which crossed wild-type Drosophila (CS10) with c765-gal4 and CS10 to analyze the phenotype of the c765-Gal4 cancer growth blackfly flies model. As a result of comparing the blade lengths of c765-Gal4 / + CS10, UAS-Ras85D / + CS10; The wing length of c765-Gal4 / + CS10 was longer than that of the three control groups. The wing length was compared with the length of the chest to compensate for the difference between the individual flies. That is, a cancer proliferation assay model (see FIG. 8 below)

[Example 9: Influence of inhibition of AGL gene expression on phenotype in cancer growth model flies (UAS-PI3K; c765-Gal4)] [

In order to estimate the effect of inhibition of AGL gene expression on cancer growth, the wing phenotype of the F1 generation obtained by crossing the cancer growth model Drosophila (UAS-PI3K; c765-Gal4) and UAS-AGL RNAi Drosophila was examined. As a result, it was confirmed that the increased blade length and area due to PI3K overexpression were significantly reduced when the expression of AGL was inhibited (see FIGS. 9 and 10 below).

[Example 10: Influence of inhibition of AGL gene expression on phenotype in cancer proliferation model floss (UAS-Ras85D; c765-Gal4)] [

In order to estimate the effect of inhibition of AGL gene expression on cancer growth, the wing phenotype of the F1 generation obtained by crossing the cancer growth model flies (UAS-Ras85D; c765-Gal4) with the UAS-AGL RNAi Drosophila was examined. As a result, it was confirmed that the increased blade length and area due to overexpression of Ras85D decreased significantly when the expression of AGL was suppressed (see FIGS. 11 'and 12').

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. It is natural.

<110> Korea University Research and Business Foundation <120> AGL gene common associating life-reduction, cancer and obesity <130> HPC-6031 <160> 12 <170> KoPatentin 3.0 <210> 1 <211> 4890 <212> DNA <213> Drosophila sp. <400> 1 atgcgttatc agctcttccg atggctttat ggactaatag cgactgttga taacgaaccg 60 ctaccgttac aaatcaaaag cgaagaggaa gcgttcgggg aaaacaagaa gaagaagcag 120 ctggcgagtc tggagaatgc catctccccc ggaaaattgg attcagtcgc gattagaacc 180 gttccaagtg caaatgcgaa tgcaatgggc aatgcaggca gtgccgagat cgtatcaaat 240 caaatcatcc gccgccgtga gatgagcacc atgggcaagg agacggagtc gcatagcata 300 cccatcagcg agggccagga tgcggagcat atcctgtacc gtctgaagcg gggttccaag 360 ctgagtgttc atccggatgc ctcgttgctg ggcaggaaga tcgtattgta caccaactat 420 cccgccgagg gacagaagtt tgtgcgtacg gagtatcgcg tgctgggatg gcaactcagc 480 aatggcaagc agattacctc tgtaatgcat ccggaggccc atgtggtaga tactgacatt 540 cgtagtcagg tggagctcaa catgtccggc acctaccact tttacttccg gtatctggaa 600 agacccgaca ctggctgctc cggagcagat ggagctctat atgtgcaagt ggagcccacg 660 ctgcatgttg ggccgcctgg cgcccagaag accattccct tggactcggt gcgctgccaa 720 acggtgctgg ccaagctcct gggaccactg gacacttggg agcctaagct gcgcgtggca 780 aaggaggccg gatacaatgt gatccacttc actcccatcc aggagttggg tggctcccga 840 tcctgctatt cgctgcgtga tcaactcaag gtcaactccc attttgcacc ccaaaaggga 900 ggtaagatca gttttgagga tgtggagaag gtcatcaaga agtgccgcca ggagtggggg 960 gtggcctcca tctgcgacat cgtgctcaat cacaccgcca acgagtccga ttggctacta 1020 cagcatccgg atgccaccta ctcatgcgcc acctgtccct acctccgccc cgccttcctg 1080 ctggacgcca cattcgccca gtgcggagcg gacatagccg agggcagcct ggagcatgta 1140 ggcgtacctg cggtcatcga gcaggagtgc catttggaag cgttaaagta ccagttgcac 1200 acctcctaca tgtccaaggt caatatacac gagctgtatc agtgcgatgt gatgaagtac 1260 gtgaacgagt tcatgtccca ggtgcgaact cgcgagccac cgaagaatgt ggccaacgag 1320 tgtcgcttcc aggaaatcca actgatacag gacccgcaat atcgacgctt ggccagcacc 1380 attaatttcg agctggcgct ggagatcttt aatgctttcc atggcgactg cttcgatgag 1440 gagtcacggt tccgcaagtg cgccgaaacc ctccgccggc atctcgatgc cctcaacgat 1500 cgtgtgcgct gcgaggttca aggctacata aactatgcga tagacaatgt tttggccgga 1560 gttcgctacg aaagagtcca gggcgatggg cccagagtga aggagatctc cgagaagcac 1620 tcggtcttta tggtctactt tacgcatacc ggcacccagg gaaaatcgct cactgagatc 1680 gggcggata tgtataccaa ggctggagag ttcttcatgg cccacaacgg ttgggtcatg 1740 ggatacagcg atcctctgag ggattttgct gaggagcaac ctggacgcgc caatgtctac 1800 ctcaagcggg agctcatctc gtggggcgat agtgtgaagt tgcgcttcgg cagacggccg 1860 gaggacagtc cctacctatg gcagcacatg accgagtacg ttcagaccac agcgcgcatc 1920 ttcgacggtg tgcgattgga caactgccac tccacgccat tgcacgtagc tgagtacctt 1980 ctcgatgcag ctcgtaagat caacccagag ctgtatgtgg tggctgaact gttcaccaat 2040 tccgattaca ccgacaatgt gtttgtgaac cgattgggta tcacctcctt gatccgtgaa 2100 gctctttccg cttgggactc ccacgagcaa ggccgcttag tgtatcggta tggaggagtg 2160 cctgtaggtg gtttccaagc aaactcatcg cgccacgagg ccaccagtgt cgctcatgcc 2220 ctcttcctgg acctcaccca cgataatccg tctccggtgg agaagcgttc cgtgtacgat 2280 cttctaccat cggcggcact ggtttccatg gcatgctgtg ccacaggaag taaccgtggt 2340 tacgacgaac tggtccccca tcatatccat gtcgtagatg aggaacgcac ctaccaagaa 2400 tggggcaaag gtgttgactc gaagtccgga attatgggtg ccaaaagagc actgaatttg 2460 ctgcatggac agctcgcaga ggagggattt agccaagttt acgtagacca gatggatccc 2520 aacgtagttg cagttactcg tcattcgcca atcacgcatc agtcagttat tctcgtggcc 2580 cacactgcct ttggctatcc ctctcctaat gccggaccca ccggaatccg cccgctgcgt 2640 ttcgagggtg tgctggacga gatcatcctg gaggccagct tgaccatgca gagtgacaag 2700 ccattcgatc gtcctgctcc attcaaaaag gatccgaatg taatcaacgg ctttactcag 2760 ttccagttga atctgcagga gcacatcccg ctggctaagt cgacagtgtt tcagacccaa 2820 gcctattcgg atggcaacaa cacggagcta aactttgcca atctacgacc cggcactgtg 2880 gtggccatca gagtgtctat gcatcctggt cctcgcacca gtttcgataa gctccagaaa 2940 atctcggctg ccctgcgtat tggatctggc gaggagtatt cccagctgca ggctatcgtc 3000 tccaagttgg atctggtggc acttagtggt gcccttttca gctgcgatga tgaggagagg 3060 gatcttggca aaggtggcac cgcctacgac attcccaact ttggaaagat cgtttactgc 3120 ggattgcaag gattcatttc cctgttgacg gagatttcgc ctaaaaatga cttgggacat 3180 ccgctttgta acaatctgcg cgacggaaac tggatgatgg attacatttc tgatcgccta 3240 actagttatg aagacctgaa accactctcc gcctggttca aagctacctt tgagccactg 3300 aagaatattc cacgctacct cataccctgc tactttgatg ccattgtcag cggggtttac 3360 aatgtgctca tcaaccaggt caacgaacta atgccagact tcattaagaa tggccacagt 3420 ttcccacaat ccctggccct gtccacgttg cagttcctct ccgtttgcaa gtcggccaat 3480 ctgccgggat tcagtcctgc tctaagtcca cccaagcctc caaagcaatg tgtgactcta 3540 tctgctggtc tgccgcattt ctcaacgggc tatatgcggt gctggggccg tgataccttc 3600 atcgctctgc gtggctccat gttcctcact ggccgttaca acgaggctcg cttcatcatc 3660 attggatttg gtcagaccct tcgacacgga ctcattccga atcttttgga cagcggcagc 3720 aagccgagat tcaactgccg cgatgctatc tggtggtgga tgtactgcat caagcagtat 3780 gtggaggatg cccccaaggg tgccgagatc ctgaaggaca aggtgtcccg catatttccg 3840 tacgacgatg ccgatgccca tgctccaggt gccttcgacc aacttctctt cgacgtgatg 3900 caggaggcac tgcaggtgca ttttcagggc ttgcagtata gggagcgcaa tgcaggctat 3960 gagatcgatg cgcacatggt ggaccagggc tttaacaatc agatcggaat tcacccggag 4020 actggctttg tattcggagg caataacttc aactgcggca cttggatgga caaaatggga 4080 tcctcacaga aggccggaaa caagggacgt ccaagtacgc cgcgcgacgg atcagccgtg 4140 gagctcgttg gcctccagta tgccgtactc cggtttatgc aaagcctagc cgaaaaggag 4200 gttatcccgt acaccggcgt ggaacgaaag ggtccatcgg gcgaagtgac caagtggagc 4260 tacaaggagt gggcggatcg catcaagaac aactttgaca agtatttctt tgtatccgaa 4320 tcggaaacct gctcggtggc caacaagaag cttatctaca aggacagcta tggagccacc 4380 cagagttgga cggactacca gctgcgatgc aacttcccca tcaccttgac cgtggctccc 4440 gcctgtgca atcctcagaa tgcctggcgt gcactggagc gcgccaaaaa gtatcttctg 4500 ggaccgctgg gcatgaagac gatggatccc gaggactgga actatagggc caactatgac 4560 aactcaaatg actccaccga ttgcactgta gcccatggcg caaactacca ccaggggccg 4620 gagtgggtat ggcccatcgg tttttacctg cgggcgcgcc tgatcttcgc caaaaagtgt 4680 ggccatttgg acgagaccat tgccgagacc tgggccatac tacgggccca tctccgagag 4740 ctacagacat cccattggcg cggattgccc gagttgacca acgataatgg ctcctactgc 4800 ggtgactcct gtcgcacgca ggcctggagt gttgctgcca ttttggaagt cctgtacgat 4860 ctgcactcct tgggagcaga cgtggcctaa 4890 <210> 2 <211> 4629 <212> DNA <213> Drosophila sp. <400> 2 atgagcacca tgggcaagga gacggagtcg catagcatac ccatcagcga gggccaggat 60 gcggagcata tcctgtaccg tctgaagcgg ggttccaagc tgagtgttca tccggatgcc 120 tcgttgctgg gcaggaagat cgtattgtac accaactatc ccgccgaggg acagaagttt 180 gtgcgtacgg agtatcgcgt gctgggatgg caactcagca atggcaagca gattacctct 240 gtaatgcatc cggaggccca tgtggtagat actgacattc gtagtcaggt ggagctcaac 300 atgtccggca cctaccactt ttacttccgg tatctggaaa gacccgacac tggctgctcc 360 ggagcagatg gagctctata tgtgcaagtg gagcccacgc tgcatgttgg gccgcctggc 420 gcccagaaga ccattccctt ggactcggtg cgctgccaaa cggtgctggc caagctcctg 480 ggaccactgg acacttggga gcctaagctg cgcgtggcaa aggaggccgg atacaatgtg 540 atccacttca ctcccatcca ggagttgggt ggctcccgat cctgctattc gctgcgtgat 600 caactcaagg tcaactccca ttttgcaccc caaaagggag gtaagatcag ttttgaggat 660 gtggagaagg tcatcaagaa gtgccgccag gagtgggggg tggcctccat ctgcgacatc 720 gtgctcaatc acaccgccaa cgagtccgat tggctactac agcatccgga tgccacctac 780 tcatgcgcca cctgtcccta cctccgcccc gccttcctgc tggacgccac attcgcccag 840 tgcggagcgg acatagccga gggcagcctg gagcatgtag gcgtacctgc ggtcatcgag 900 caggagtgcc atttggaagc gttaaagtac cagttgcaca cctcctacat gtccaaggtc 960 aatatacacg agctgtatca gtgcgatgtg atgaagtacg tgaacgagtt catgtcccag 1020 gtgcgaactc gcgagccacc gaagaatgtg gccaacgagt gtcgcttcca ggaaatccaa 1080 ctgatacagg acccgcaata tcgacgcttg gccagcacca ttaatttcga gctggcgctg 1140 gagatcttta atgctttcca tggcgactgc ttcgatgagg agtcacggtt ccgcaagtgc 1200 gccgaaaccc tccgccggca tctcgatgcc ctcaacgatc gtgtgcgctg cgaggttcaa 1260 ggctacataa actatgcgat agacaatgtt ttggccggag ttcgctacga aagagtccag 1320 ggcgatgggc ccagagtgaa ggagatctcc gagaagcact cggtctttat ggtctacttt 1380 acgcataccg gcacccaggg aaaatcgctc actgagatcg aggcggatat gtataccaag 1440 gctggagagt tcttcatggc ccacaacggt tgggtcatgg gatacagcga tcctctgagg 1500 gattttgctg aggagcaacc tggacgcgcc aatgtctacc tcaagcggga gctcatctcg 1560 tggggcgata gtgtgaagtt gcgcttcggc agacggccgg aggacagtcc ctacctatgg 1620 cagcacatga ccgagtacgt tcagaccaca gcgcgcatct tcgacggtgt gcgattggac 1680 aactgccact ccacgccatt gcacgtagct gagtaccttc tcgatgcagc tcgtaagatc 1740 aacccagagc tgtatgtggt ggctgaactg ttcaccaatt ccgattacac cgacaatgtg 1800 tttgtgaacc gattgggtat cacctccttg atccgtgaag ctctttccgc ttgggactcc 1860 cacgagcaag gccgcttagt gtatcggtat ggaggagtgc ctgtaggtgg tttccaagca 1920 aactcatcgc gccacgaggc caccagtgtc gctcatgccc tcttcctgga cctcacccac 1980 gataatccgt ctccggtgga gaagcgttcc gtgtacgatc ttctaccatc ggcggcactg 2040 gtttccatgg catgctgtgc cacaggaagt aaccgtggtt acgacgaact ggtcccccat 2100 catatccatg tcgtagatga ggaacgcacc taccaagaat ggggcaaagg tgttgactcg 2160 aagtccggaa ttatgggtgc caaaagagca ctgaatttgc tgcatggaca gctcgcagag 2220 gagggattta gccaagttta cgtagaccag atggatccca acgtagttgc agttactcgt 2280 cattcgccaa tcacgcatca gtcagttatt ctcgtggccc acactgcctt tggctatccc 2340 tctcctaatg ccggacccac cggaatccgc ccgctgcgtt tcgagggtgt gctggacgag 2400 atcatcctgg aggccagctt gaccatgcag agtgacaagc cattcgatcg tcctgctcca 2460 ttcaaaaagg atccgaatgt aatcaacggc tttactcagt tccagttgaa tctgcaggag 2520 cacatcccgc tggctaagtc gacagtgttt cagacccaag cctattcgga tggcaacaac 2580 acggagctaa actttgccaa tctacgaccc ggcactgtgg tggccatcag agtgtctatg 2640 catcctggtc ctcgcaccag tttcgataag ctccagaaaa tctcggctgc cctgcgtatt 2700 ggatctggcg aggagtattc ccagctgcag gctatcgtct ccaagttgga tctggtggca 2760 cttagtggtg cccttttcag ctgcgatgat gaggagaggg atcttggcaa aggtggcacc 2820 gcctacgaca ttcccaactt tggaaagatc gtttactgcg gattgcaagg attcatttcc 2880 ctgttgacgg agatttcgcc taaaaatgac ttgggacatc cgctttgtaa caatctgcgc 2940 gacggaaact ggatgatgga ttacatttct gatcgcctaa ctagttatga agacctgaaa 3000 ccactctccg cctggttcaa agctaccttt gagccactga agaatattcc acgctacctc 3060 ataccctgct actttgatgc cattgtcagc ggggtttaca atgtgctcat caaccaggtc 3120 aacgaactaa tgccagactt cattaagaat ggccacagtt tcccacaatc cctggccctg 3180 tccacgttgc agttcctctc cgtttgcaag tcggccaatc tgccgggatt cagtcctgct 3240 ctaagtccac ccaagcctcc aaagcaatgt gtgactctat ctgctggtct gccgcatttc 3300 tcaacgggct atatgcggtg ctggggccgt gataccttca tcgctctgcg tggctccatg 3360 ttcctcactg gccgttacaa cgaggctcgc ttcatcatca ttggatttgg tcagaccctt 3420 cgacacggac tcattccgaa tcttttggac agcggcagca agccgagatt caactgccgc 3480 gatgctatct ggtggtggat gtactgcatc aagcagtatg tggaggatgc ccccaagggt 3540 gccgagatcc tgaaggacaa ggtgtcccgc atatttccgt acgacgatgc cgatgcccat 3600 gctccaggtg ccttcgacca acttctcttc gacgtgatgc aggaggcact gcaggtgcat 3660 tttcagggct tgcagtatag ggagcgcaat gcaggctatg agatcgatgc gcacatggtg 3720 gaccagggct ttaacaatca gatcggaatt cacccggaga ctggctttgt attcggaggc 3780 aataacttca actgcggcac ttggatggac aaaatgggat cctcacagaa ggccggaaac 3840 aagggacgtc caagtacgcc gcgcgacgga tcagccgtgg agctcgttgg cctccagtat 3900 gccgtactcc ggtttatgca aagcctagcc gaaaaggagg ttatcccgta caccggcgtg 3960 gaacgaaagg gtccatcggg cgaagtgacc aagtggagct acaaggagtg ggcggatcgc 4020 atcaagaaca actttgacaa gtatttcttt gtatccgaat cggaaacctg ctcggtggcc 4080 aacaagaagc ttatctacaa ggacagctat ggagccaccc agagttggac ggactaccag 4140 ctgcgatgca acttccccat caccttgacc gtggctcccg acctgtgcaa tcctcagaat 4200 gcctggcgtg cactggagcg cgccaaaaag tatcttctgg gaccgctggg catgaagacg 4260 atggatcccg aggactggaa ctatagggcc aactatgaca actcaaatga ctccaccgat 4320 tgcactgtag cccatggcgc aaactaccac caggggccgg agtgggtatg gcccatcggt 4380 ttttacctgc gggcgcgcct gatcttcgcc aaaaagtgtg gccatttgga cgagaccatt 4440 gccgagacct gggccatact acgggcccat ctccgagagc tacagacatc ccattggcgc 4500 ggattgcccg agttgaccaa cgataatggc tcctactgcg gtgactcctg tcgcacgcag 4560 gcctggagtg ttgctgccat tttggaagtc ctgtacgatc tgcactcctt gggagcagac 4620 gtggcctaa 4629 <210> 3 <211> 4641 <212> DNA <213> Drosophila sp. <400> 3 atgcctttgg ctatgagcac catgggcaag gagacggagt cgcatagcat acccatcagc 60 gagggccagg atgcggagca tatcctgtac cgtctgaagc ggggttccaa gctgagtgtt 120 catccggatg cctcgttgct gggcaggaag atcgtattgt acaccaacta tcccgccgag 180 ggacagaagt ttgtgcgtac ggagtatcgc gtgctgggat ggcaactcag caatggcaag 240 cagattacct ctgtaatgca tccggaggcc catgtggtag atactgacat tcgtagtcag 300 gtggagctca acatgtccgg cacctaccac ttttacttcc ggtatctgga aagacccgac 360 actggctgct ccggagcaga tggagctcta tatgtgcaag tggagcccac gctgcatgtt 420 gggccgcctg gcgcccagaa gaccattccc ttggactcgg tgcgctgcca aacggtgctg 480 gccaagctcc tgggaccact ggacacttgg gagcctaagc tgcgcgtggc aaaggaggcc 540 ggatacaatg tgatccactt cactcccatc caggagttgg gtggctcccg atcctgctat 600 tcgctgcgtg atcaactcaa ggtcaactcc cattttgcac cccaaaaggg aggtaagatc 660 agttttgagg atgtggagaa ggtcatcaag aagtgccgcc aggagtgggg ggtggcctcc 720 atctgcgaca tcgtgctcaa tcacaccgcc aacgagtccg attggctact acagcatccg 780 gatgccacct actcatgcgc cacctgtccc tacctccgcc ccgccttcct gctggacgcc 840 acattcgccc agtgcggagc ggacatagcc gagggcagcc tggagcatgt aggcgtacct 900 gcggtcatcg agcaggagtg ccatttggaa gcgttaaagt accagttgca cacctcctac 960 atgtccaagg tcaatataca cgagctgtat cagtgcgatg tgatgaagta cgtgaacgag 1020 ttcatgtccc aggtgcgaac tcgcgagcca ccgaagaatg tggccaacga gtgtcgcttc 1080 caggaaatcc aactgataca ggacccgcaa tatcgacgct tggccagcac cattaatttc 1140 gagctggcgc tggagatctt taatgctttc catggcgact gcttcgatga ggagtcacgg 1200 ttccgcaagt gcgccgaaac cctccgccgg catctcgatg ccctcaacga tcgtgtgcgc 1260 tgcgaggttc aaggctacat aaactatgcg atagacaatg ttttggccgg agttcgctac 1320 gaaagagtcc agggcgatgg gcccagagtg aaggagatct ccgagaagca ctcggtcttt 1380 atggtctact ttacgcatac cggcacccag ggaaaatcgc tcactgagat cgaggcggat 1440 atgtatacca aggctggaga gttcttcatg gcccacaacg gttgggtcat gggatacagc 1500 gatcctctga gggattttgc tgaggagcaa cctggacgcg ccaatgtcta cctcaagcgg 1560 gagctcatct cgtggggcga tagtgtgaag ttgcgcttcg gcagacggcc ggaggacagt 1620 ccctacctat ggcagcacat gccgagtac gttcagacca cagcgcgcat cttcgacggt 1680 gtgcgattgg acaactgcca ctccacgcca ttgcacgtag ctgagtacct tctcgatgca 1740 gctcgtaaga tcaacccaga gctgtatgtg gtggctgaac tgttcaccaa ttccgattac 1800 accgacaatg tgtttgtgaa ccgattgggt atcacctcct tgatccgtga agctctttcc 1860 gcttgggact cccacgagca aggccgctta gtgtatcggt atggaggagt gcctgtaggt 1920 ggtttccaag caaactcatc gcgccacgag gccaccagtg tcgctcatgc cctcttcctg 1980 gacctcaccc acgataatcc gtctccggtg gagaagcgtt ccgtgtacga tcttctacca 2040 tcggcggcac tggtttccat ggcatgctgt gccacaggaa gtaaccgtgg ttacgacgaa 2100 ctggtccccc atcatatcca tgtcgtagat gaggaacgca cctaccaaga atggggcaaa 2160 ggtgttgact cgaagtccgg aattatgggt gccaaaagag cactgaattt gctgcatgga 2220 cagctcgcag aggagggatt tagccaagtt tacgtagacc agatggatcc caacgtagtt 2280 gcagttactc gtcattcgcc aatcacgcat cagtcagtta ttctcgtggc ccacactgcc 2340 tttggctatc cctctcctaa tgccggaccc accggaatcc gcccgctgcg tttcgagggt 2400 gtgctggacg agatcatcct ggaggccagc ttgaccatgc agagtgacaa gccattcgat 2460 cgtcctgctc cattcaaaaa ggatccgaat gtaatcaacg gctttactca gttccagttg 2520 aatctgcagg agcacatccc gctggctaag tcgacagtgt ttcagaccca agcctattcg 2580 gatggcaaca acacggagct aaactttgcc aatctacgac ccggcactgt ggtggccatc 2640 agagtgtcta tgcatcctgg tcctcgcacc agtttcgata agctccagaa aatctcggct 2700 gccctgcgta ttggatctgg cgaggagtat tcccagctgc aggctatcgt ctccaagttg 2760 gatctggtgg cacttagtgg tgcccttttc agctgcgatg atgaggagag ggatcttggc 2820 aaaggtggca ccgcctacga cattcccaac tttggaaaga tcgtttactg cggattgcaa 2880 ggattcattt ccctgttgac ggagatttcg cctaaaaatg acttgggaca tccgctttgt 2940 aacaatctgc gcgacggaaa ctggatgatg gattacattt ctgatcgcct aactagttat 3000 gaagacctga aaccactctc cgcctggttc aaagctacct ttgagccact gaagaatatt 3060 ccacgctacc tcataccctg ctactttgat gccattgtca gcggggttta caatgtgctc 3120 atcaaccagg tcaacgaact aatgccagac ttcattaaga atggccacag tttcccacaa 3180 tccctggccc tgtccacgtt gcagttcctc tccgtttgca agtcggccaa tctgccggga 3240 ttcagtcctg ctctaagtcc acccaagcct ccaaagcaat gtgtgactct atctgctggt 3300 ctgccgcatt tctcaacggg ctatatgcgg tgctggggcc gtgatacctt catcgctctg 3360 cgtggctcca tgttcctcac tggccgttac aacgaggctc gcttcatcat cattggattt 3420 ggtcagaccc ttcgacacgg actcattccg aatcttttgg acagcggcag caagccgaga 3480 ttcaactgcc gcgatgctat ctggtggtgg atgtactgca tcaagcagta tgtggaggat 3540 gcccccaagg gtgccgagat cctgaaggac aaggtgtccc gcatatttcc gtacgacgat 3600 gccgatgccc atgctccagg tgccttcgac caacttctct tcgacgtgat gcaggaggca 3660 ctgcaggtgc attttcaggg cttgcagtat agggagcgca atgcaggcta tgagatcgat 3720 gcgcacatgg tggaccaggg ctttaacaat cagatcggaa ttcacccgga gactggcttt 3780 gtattcggag gcaataactt caactgcggc acttggatgg acaaaatggg atcctcacag 3840 aaggccggaa acaagggacg tccaagtacg ccgcgcgacg gatcagccgt ggagctcgtt 3900 ggcctccagt atgccgtact ccggtttatg caaagcctag ccgaaaagga ggttatcccg 3960 tacaccggcg tggaacgaaa gggtccatcg ggcgaagtga ccaagtggag ctacaaggag 4020 tgggcggatc gcatcaagaa caactttgac aagtatttct ttgtatccga atcggaaacc 4080 tgctcggtgg ccaacaagaa gcttatctac aaggacagct atggagccac ccagagttgg 4140 acggactacc agctgcgatg caacttcccc atcaccttga ccgtggctcc cgacctgtgc 4200 aatcctcaga atgcctggcg tgcactggag cgcgccaaaa agtatcttct gggaccgctg 4260 ggcatgaaga cgatggatcc cgaggactgg aactataggg ccaactatga caactcaaat 4320 gactccaccg attgcactgt agcccatggc gcaaactacc accaggggcc ggagtgggta 4380 tggcccatcg gtttttacct gcgggcgcgc ctgatcttcg ccaaaaagtg tggccatttg 4440 gcgagacca ttgccgagac ctgggccata ctacgggccc atctccgaga gctacagaca 4500 tcccattggc gcggattgcc cgagttgacc aacgataatg gctcctactg cggtgactcc 4560 tgtcgcacgc aggcctggag tgttgctgcc attttggaag tcctgtacga tctgcactcc 4620 ttgggagcag acgtggccta a 4641 <210> 4 <211> 4692 <212> DNA <213> Drosophila sp. <400> 4 atgagcacca tgggcaagga gacggagtcg catagcatac ccatcagcga gggccaggat 60 gcggagcata tcctgtaccg tctgaagcgg ggttccaagc tgagtgttca tccggatgcc 120 tcgttgctgg gcaggaagat cgtattgtac accaactatc ccgccgaggg acagaagttt 180 gtgcgtacgg agtatcgcgt gctgggatgg caactcagca atggcaagca gattacctct 240 gtaatgcatc cggaggccca tgtggtagat actgacattc gtagtcaggt ggagctcaac 300 atgtccggca cctaccactt ttacttccgg tatctggaaa ggttcgaaac tatacttttc 360 cgcattgatt ttgctttagc attaatgtgt gtcaacattt tcagacccga cactggctgc 420 tccggagcag atggagctct atatgtgcaa gtggagccca cgctgcatgt tgggccgcct 480 ggcgcccaga agaccattcc cttggactcg gtgcgctgcc aaacggtgct ggccaagctc 540 ctgggaccac tggacacttg ggagcctaag ctgcgcgtgg caaaggaggc cggatacaat 600 gtgatccact tcactcccat ccaggagttg ggtggctccc gatcctgcta ttcgctgcgt 660 gatcaactca aggtcaactc ccattttgca ccccaaaagg gaggtaagat cagttttgag 720 gatgtggaga aggtcatcaa gaagtgccgc caggagtggg gggtggcctc catctgcgac 780 atcgtgctca atcacaccgc caacgagtcc gattggctac tacagcatcc ggatgccacc 840 tactcatgcg ccacctgtcc ctacctccgc cccgccttcc tgctggacgc cacattcgcc 900 cgtgcggag cggacatagc cgagggcagc ctggagcatg taggcgtacc tgcggtcatc 960 gagcaggagt gccatttgga agcgttaaag taccagttgc acacctccta catgtccaag 1020 gtcaatatac acgagctgta tcagtgcgat gtgatgaagt acgtgaacga gttcatgtcc 1080 caggtgcgaa ctcgcgagcc accgaagaat gtggccaacg agtgtcgctt ccaggaaatc 1140 caactgatac aggacccgca atatcgacgc ttggccagca ccattaattt cgagctggcg 1200 ctggagatct ttaatgcttt ccatggcgac tgcttcgatg aggagtcacg gttccgcaag 1260 tgcgccgaaa ccctccgccg gcatctcgat gccctcaacg atcgtgtgcg ctgcgaggtt 1320 caaggctaca taaactatgc gatagacaat gttttggccg gagttcgcta cgaaagagtc 1380 cagggcgatg ggcccagagt gaaggagatc tccgagaagc actcggtctt tatggtctac 1440 tttacgcata ccggcaccca gggaaaatcg ctcactgaga tcgaggcgga tatgtatacc 1500 aaggctggag agttcttcat ggcccacaac ggttgggtca tgggatacag cgatcctctg 1560 agggattttg ctgaggagca acctggacgc gccaatgtct acctcaagcg ggagctcatc 1620 tcgtggggcg atagtgtgaa gttgcgcttc ggcagacggc cggaggacag tccctaccta 1680 tggcagcaca tgaccgagta cgttcagacc acagcgcgca tcttcgacgg tgtgcgattg 1740 gacaactgcc actccacgcc attgcacgta gctgagtacc ttctcgatgc agctcgtaag 1800 atcaacccag agctgtatgt ggtggctgaa ctgttcacca attccgatta caccgacaat 1860 gtgtttgtga accgattggg tatcacctcc ttgatccgtg aagctctttc cgcttgggac 1920 tcccacgagc aaggccgctt agtgtatcgg tatggaggag tgcctgtagg tggtttccaa 1980 gcaaactcat cgcgccacga ggccaccagt gtcgctcatg ccctcttcct ggacctcacc 2040 ccgataatc cgtctccggt ggagaagcgt tccgtgtacg atcttctacc atcggcggca 2100 ctggtttcca tggcatgctg tgccacagga agtaaccgtg gttacgacga actggtcccc 2160 catcatatcc atgtcgtaga tgaggaacgc acctaccaag aatggggcaa aggtgttgac 2220 tcgaagtccg gaattatggg tgccaaaaga gcactgaatt tgctgcatgg acagctcgca 2280 gaggagggat ttagccaagt ttacgtagac cagatggatc ccaacgtagt tgcagttact 2340 cgtcattcgc caatcacgca tcagtcagtt attctcgtgg cccacactgc ctttggctat 2400 ccctctccta atgccggacc caccggaatc cgcccgctgc gtttcgaggg tgtgctggac 2460 gagatcatcc tggaggccag cttgaccatg cagagtgaca agccattcga tcgtcctgct 2520 ccattcaaaa aggatccgaa tgtaatcaac ggctttactc agttccagtt gaatctgcag 2580 gagcacatcc cgctggctaa gtcgacagtg tttcagaccc aagcctattc ggatggcaac 2640 aacacggagc taaactttgc caatctacga cccggcactg tggtggccat cagagtgtct 2700 atgcatcctg gtcctcgcac cagtttcgat aagctccaga aaatctcggc tgccctgcgt 2760 attggatctg gcgaggagta ttcccagctg caggctatcg tctccaagtt ggatctggtg 2820 gcacttagtg gtgccctttt cagctgcgat gatgaggaga gggatcttgg caaaggtggc 2880 accgcctacg acattcccaa ctttggaaag atcgtttact gcggattgca aggattcatt 2940 tccctgttga cggagatttc gcctaaaaat gacttgggac atccgctttg taacaatctg 3000 cgcgacggaa actggatgat ggattacatt tctgatcgcc taactagtta tgaagacctg 3060 aaaccactct ccgcctggtt caaagctacc tttgagccac tgaagaatat tccacgctac 3120 ctcataccct gctactttga tgccattgtc agcggggttt acaatgtgct catcaaccag 3180 gtcaacgaac taatgccaga cttcattaag aatggccaca gtttcccaca atccctggcc 3240 ctgtccacgt tgcagttcct ctccgtttgc aagtcggcca atctgccggg attcagtcct 3300 gctctaagtc cacccaagcc tccaaagcaa tgtgtgactc tatctgctgg tctgccgcat 3360 ttctcaacgg gctatatgcg gtgctggggc cgtgatacct tcatcgctct gcgtggctcc 3420 atgttcctca ctggccgtta caacgaggct cgcttcatca tcattggatt tggtcagacc 3480 cttcgacacg gactcattcc gaatcttttg gacagcggca gcaagccgag attcaactgc 3540 cgcgatgcta tctggtggtg gatgtactgc atcaagcagt atgtggagga tgcccccaag 3600 ggtgccgaga tcctgaagga caaggtgtcc cgcatatttc cgtacgacga tgccgatgcc 3660 catgctccag gtgccttcga ccaacttctc ttcgacgtga tgcaggaggc actgcaggtg 3720 cattttcagg gcttgcagta tagggagcgc aatgcaggct atgagatcga tgcgcacatg 3780 gtggaccagg gctttaacaa tcagatcgga attcacccgg agactggctt tgtattcgga 3840 ggcaataact tcaactgcgg cacttggatg gacaaaatgg gatcctcaca gaaggccgga 3900 aacaagggac gtccaagtac gccgcgcgac ggatcagccg tggagctcgt tggcctccag 3960 tatgccgtac tccggtttat gcaaagccta gccgaaaagg aggttatccc gtacaccggc 4020 gtggaacgaa agggtccatc gggcgaagtg accaagtgga gctacaagga gtgggcggat 4080 cgcatcaaga acaactttga caagtatttc tttgtatccg aatcggaaac ctgctcggtg 4140 gccaacaaga agcttatcta caaggacagc tatggagcca cccagagttg gacggactac 4200 cagctgcgat gcaacttccc catcaccttg accgtggctc ccgacctgtg caatcctcag 4260 aatgcctggc gtgcactgga gcgcgccaaa aagtatcttc tgggaccgct gggcatgaag 4320 acgatggatc ccgaggactg gaactatagg gccaactatg acaactcaaa tgactccacc 4380 gattgcactg tagcccatgg cgcaaactac caccaggggc cggagtgggt atggcccatc 4440 ggtttttacc tgcgggcgcg cctgatcttc gccaaaaagt gtggccattt ggacgagacc 4500 attgccgaga cctgggccat actacgggcc catctccgag agctacagac atcccattgg 4560 cgcggattgc ccgagttgac caacgataat ggctcctact gcggtgactc ctgtcgcacg 4620 caggcctgga gtgttgctgc cattttggaa gtcctgtacg atctgcactc cttgggag 4680 gacgtggcct aa 4692 <210> 5 <211> 4629 <212> DNA <213> Drosophila sp. <400> 5 atgagcacca tgggcaagga gacggagtcg catagcatac ccatcagcga gggccaggat 60 gcggagcata tcctgtaccg tctgaagcgg ggttccaagc tgagtgttca tccggatgcc 120 tcgttgctgg gcaggaagat cgtattgtac accaactatc ccgccgaggg acagaagttt 180 gtgcgtacgg agtatcgcgt gctgggatgg caactcagca atggcaagca gattacctct 240 gtaatgcatc cggaggccca tgtggtagat actgacattc gtagtcaggt ggagctcaac 300 atgtccggca cctaccactt ttacttccgg tatctggaaa gacccgacac tggctgctcc 360 ggagcagatg gagctctata tgtgcaagtg gagcccacgc tgcatgttgg gccgcctggc 420 gcccagaaga ccattccctt ggactcggtg cgctgccaaa cggtgctggc caagctcctg 480 ggaccactgg acacttggga gcctaagctg cgcgtggcaa aggaggccgg atacaatgtg 540 atccacttca ctcccatcca ggagttgggt ggctcccgat cctgctattc gctgcgtgat 600 caactcaagg tcaactccca ttttgcaccc caaaagggag gtaagatcag ttttgaggat 660 gtggagaagg tcatcaagaa gtgccgccag gagtgggggg tggcctccat ctgcgacatc 720 gtgctcaatc acaccgccaa cgagtccgat tggctactac agcatccgga tgccacctac 780 tcatgcgcca cctgtcccta cctccgcccc gccttcctgc tggacgccac attcgcccag 840 tgcggagcgg acatagccga gggcagcctg gagcatgtag gcgtacctgc ggtcatcgag 900 caggagtgcc atttggaagc gttaaagtac cagttgcaca cctcctacat gtccaaggtc 960 aatatacacg agctgtatca gtgcgatgtg atgaagtacg tgaacgagtt catgtcccag 1020 gtgcgaactc gcgagccacc gaagaatgtg gccaacgagt gtcgcttcca ggaaatccaa 1080 ctgatacagg acccgcaata tcgacgcttg gccagcacca ttaatttcga gctggcgctg 1140 gagatcttta atgctttcca tggcgactgc ttcgatgagg agtcacggtt ccgcaagtgc 1200 gccgaaaccc tccgccggca tctcgatgcc ctcaacgatc gtgtgcgctg cgaggttcaa 1260 ggctacataa actatgcgat agacaatgtt ttggccggag ttcgctacga aagagtccag 1320 ggcgatgggc ccagagtgaa ggagatctcc gagaagcact cggtctttat ggtctacttt 1380 acgcataccg gcacccaggg aaaatcgctc actgagatcg aggcggatat gtataccaag 1440 gctggagagt tcttcatggc ccacaacggt tgggtcatgg gatacagcga tcctctgagg 1500 gattttgctg aggagcaacc tggacgcgcc aatgtctacc tcaagcggga gctcatctcg 1560 tggggcgata gtgtgaagtt gcgcttcggc agacggccgg aggacagtcc ctacctatgg 1620 cagcacatga ccgagtacgt tcagaccaca gcgcgcatct tcgacggtgt gcgattggac 1680 aactgccact ccacgccatt gcacgtagct gagtaccttc tcgatgcagc tcgtaagatc 1740 aacccagagc tgtatgtggt ggctgaactg ttcaccaatt ccgattacac cgacaatgtg 1800 tttgtgaacc gattgggtat cacctccttg atccgtgaag ctctttccgc ttgggactcc 1860 cacgagcaag gccgcttagt gtatcggtat ggaggagtgc ctgtaggtgg tttccaagca 1920 aactcatcgc gccacgaggc caccagtgtc gctcatgccc tcttcctgga cctcacccac 1980 gataatccgt ctccggtgga gaagcgttcc gtgtacgatc ttctaccatc ggcggcactg 2040 gtttccatgg catgctgtgc cacaggaagt aaccgtggtt acgacgaact ggtcccccat 2100 catatccatg tcgtagatga ggaacgcacc taccaagaat ggggcaaagg tgttgactcg 2160 aagtccggaa ttatgggtgc caaaagagca ctgaatttgc tgcatggaca gctcgcagag 2220 gagggattta gccaagttta cgtagaccag atggatccca acgtagttgc agttactcgt 2280 cattcgccaa tcacgcatca gtcagttatt ctcgtggccc acactgcctt tggctatccc 2340 tctcctaatg ccggacccac cggaatccgc ccgctgcgtt tcgagggtgt gctggacgag 2400 atcatcctgg aggccagctt gaccatgcag agtgacaagc cattcgatcg tcctgctcca 2460 ttcaaaaagg atccgaatgt aatcaacggc tttactcagt tccagttgaa tctgcaggag 2520 cacatcccgc tggctaagtc gacagtgttt cagacccaag cctattcgga tggcaacaac 2580 acggagctaa actttgccaa tctacgaccc ggcactgtgg tggccatcag agtgtctatg 2640 catcctggtc ctcgcaccag tttcgataag ctccagaaaa tctcggctgc cctgcgtatt 2700 ggatctggcg aggagtattc ccagctgcag gctatcgtct ccaagttgga tctggtggca 2760 cttagtggtg cccttttcag ctgcgatgat gaggagaggg atcttggcaa aggtggcacc 2820 gcctacgaca ttcccaactt tggaaagatc gtttactgcg gattgcaagg attcatttcc 2880 ctgttgacgg agatttcgcc taaaaatgac ttgggacatc cgctttgtaa caatctgcgc 2940 gacggaaact ggatgatgga ttacatttct gatcgcctaa ctagttatga agacctgaaa 3000 ccactctccg cctggttcaa agctaccttt gagccactga agaatattcc acgctacctc 3060 ataccctgct actttgatgc cattgtcagc ggggtttaca atgtgctcat caaccaggtc 3120 aacgaactaa tgccagactt cattaagaat ggccacagtt tcccacaatc cctggccctg 3180 tccacgttgc agttcctctc cgtttgcaag tcggccaatc tgccgggatt cagtcctgct 3240 ctaagtccac ccaagcctcc aaagcaatgt gtgactctat ctgctggtct gccgcatttc 3300 tcaacgggct atatgcggtg ctggggccgt gataccttca tcgctctgcg tggctccatg 3360 ttcctcactg gccgttacaa cgaggctcgc ttcatcatca ttggatttgg tcagaccctt 3420 cgacacggac tcattccgaa tcttttggac agcggcagca agccgagatt caactgccgc 3480 gatgctatct ggtggtggat gtactgcatc aagcagtatg tggaggatgc ccccaagggt 3540 gccgagatcc tgaaggacaa ggtgtcccgc atatttccgt acgacgatgc cgatgcccat 3600 gctccaggtg ccttcgacca acttctcttc gacgtgatgc aggaggcact gcaggtgcat 3660 tttcagggct tgcagtatag ggagcgcaat gcaggctatg agatcgatgc gcacatggtg 3720 gaccagggct ttaacaatca gatcggaatt cacccggaga ctggctttgt attcggaggc 3780 aataacttca actgcggcac ttggatggac aaaatgggat cctcacagaa ggccggaaac 3840 aagggacgtc caagtacgcc gcgcgacgga tcagccgtgg agctcgttgg cctccagtat 3900 gccgtactcc ggtttatgca aagcctagcc gaaaaggagg ttatcccgta caccggcgtg 3960 gaacgaaagg gtccatcggg cgaagtgacc aagtggagct acaaggagtg ggcggatcgc 4020 atcaagaaca actttgacaa gtatttcttt gtatccgaat cggaaacctg ctcggtggcc 4080 aacaagaagc ttatctacaa ggacagctat ggagccaccc agagttggac ggactaccag 4140 ctgcgatgca acttccccat caccttgacc gtggctcccg acctgtgcaa tcctcagaat 4200 gcctggcgtg cactggagcg cgccaaaaag tatcttctgg gaccgctggg catgaagacg 4260 atggatcccg aggactggaa ctatagggcc aactatgaca actcaaatga ctccaccgat 4320 tgcactgtag cccatggcgc aaactaccac caggggccgg agtgggtatg gcccatcggt 4380 ttttacctgc gggcgcgcct gatcttcgcc aaaaagtgtg gccatttgga cgagaccatt 4440 gccgagacct gggccatact acgggcccat ctccgagagc tacagacatc ccattggcgc 4500 ggattgcccg agttgaccaa cgataatggc tcctactgcg gtgactcctg tcgcacgcag 4560 gcctggagtg ttgctgccat tttggaagtc ctgtacgatc tgcactcctt gggagcagac 4620 gtggcctaa 4629 <210> 6 <211> 4629 <212> DNA <213> Drosophila sp. <400> 6 atgagcacca tgggcaagga gacggagtcg catagcatac ccatcagcga gggccaggat 60 gcggagcata tcctgtaccg tctgaagcgg ggttccaagc tgagtgttca tccggatgcc 120 tcgttgctgg gcaggaagat cgtattgtac accaactatc ccgccgaggg acagaagttt 180 gtgcgtacgg agtatcgcgt gctgggatgg caactcagca atggcaagca gattacctct 240 gtaatgcatc cggaggccca tgtggtagat actgacattc gtagtcaggt ggagctcaac 300 atgtccggca cctaccactt ttacttccgg tatctggaaa gacccgacac tggctgctcc 360 ggagcagatg gagctctata tgtgcaagtg gagcccacgc tgcatgttgg gccgcctggc 420 gcccagaaga ccattccctt ggactcggtg cgctgccaaa cggtgctggc caagctcctg 480 ggaccactgg acacttggga gcctaagctg cgcgtggcaa aggaggccgg atacaatgtg 540 atccacttca ctcccatcca ggagttgggt ggctcccgat cctgctattc gctgcgtgat 600 caactcaagg tcaactccca ttttgcaccc caaaagggag gtaagatcag ttttgaggat 660 gtggagaagg tcatcaagaa gtgccgccag gagtgggggg tggcctccat ctgcgacatc 720 gtgctcaatc acaccgccaa cgagtccgat tggctactac agcatccgga tgccacctac 780 tcatgcgcca cctgtcccta cctccgcccc gccttcctgc tggacgccac attcgcccag 840 tgcggagcgg acatagccga gggcagcctg gagcatgtag gcgtacctgc ggtcatcgag 900 caggagtgcc atttggaagc gttaaagtac cagttgcaca cctcctacat gtccaaggtc 960 aatatacacg agctgtatca gtgcgatgtg atgaagtacg tgaacgagtt catgtcccag 1020 gtgcgaactc gcgagccacc gaagaatgtg gccaacgagt gtcgcttcca ggaaatccaa 1080 ctgatacagg acccgcaata tcgacgcttg gccagcacca ttaatttcga gctggcgctg 1140 gagatcttta atgctttcca tggcgactgc ttcgatgagg agtcacggtt ccgcaagtgc 1200 gccgaaaccc tccgccggca tctcgatgcc ctcaacgatc gtgtgcgctg cgaggttcaa 1260 ggctacataa actatgcgat agacaatgtt ttggccggag ttcgctacga aagagtccag 1320 ggcgatgggc ccagagtgaa ggagatctcc gagaagcact cggtctttat ggtctacttt 1380 acgcataccg gcacccaggg aaaatcgctc actgagatcg aggcggatat gtataccaag 1440 gctggagagt tcttcatggc ccacaacggt tgggtcatgg gatacagcga tcctctgagg 1500 gattttgctg aggagcaacc tggacgcgcc aatgtctacc tcaagcggga gctcatctcg 1560 tggggcgata gtgtgaagtt gcgcttcggc agacggccgg aggacagtcc ctacctatgg 1620 cagcacatga ccgagtacgt tcagaccaca gcgcgcatct tcgacggtgt gcgattggac 1680 aactgccact ccacgccatt gcacgtagct gagtaccttc tcgatgcagc tcgtaagatc 1740 aacccagagc tgtatgtggt ggctgaactg ttcaccaatt ccgattacac cgacaatgtg 1800 tttgtgaacc gattgggtat cacctccttg atccgtgaag ctctttccgc ttgggactcc 1860 cacgagcaag gccgcttagt gtatcggtat ggaggagtgc ctgtaggtgg tttccaagca 1920 aactcatcgc gccacgaggc caccagtgtc gctcatgccc tcttcctgga cctcacccac 1980 gataatccgt ctccggtgga gaagcgttcc gtgtacgatc ttctaccatc ggcggcactg 2040 gtttccatgg catgctgtgc cacaggaagt aaccgtggtt acgacgaact ggtcccccat 2100 catatccatg tcgtagatga ggaacgcacc taccaagaat ggggcaaagg tgttgactcg 2160 aagtccggaa ttatgggtgc caaaagagca ctgaatttgc tgcatggaca gctcgcagag 2220 gagggattta gccaagttta cgtagaccag atggatccca acgtagttgc agttactcgt 2280 cattcgccaa tcacgcatca gtcagttatt ctcgtggccc acactgcctt tggctatccc 2340 tctcctaatg ccggacccac cggaatccgc ccgctgcgtt tcgagggtgt gctggacgag 2400 atcatcctgg aggccagctt gaccatgcag agtgacaagc cattcgatcg tcctgctcca 2460 ttcaaaaagg atccgaatgt aatcaacggc tttactcagt tccagttgaa tctgcaggag 2520 cacatcccgc tggctaagtc gacagtgttt cagacccaag cctattcgga tggcaacaac 2580 acggagctaa actttgccaa tctacgaccc ggcactgtgg tggccatcag agtgtctatg 2640 catcctggtc ctcgcaccag tttcgataag ctccagaaaa tctcggctgc cctgcgtatt 2700 ggatctggcg aggagtattc ccagctgcag gctatcgtct ccaagttgga tctggtggca 2760 cttagtggtg cccttttcag ctgcgatgat gaggagaggg atcttggcaa aggtggcacc 2820 gcctacgaca ttcccaactt tggaaagatc gtttactgcg gattgcaagg attcatttcc 2880 ctgttgacgg agatttcgcc taaaaatgac ttgggacatc cgctttgtaa caatctgcgc 2940 gacggaaact ggatgatgga ttacatttct gatcgcctaa ctagttatga agacctgaaa 3000 ccactctccg cctggttcaa agctaccttt gagccactga agaatattcc acgctacctc 3060 ataccctgct actttgatgc cattgtcagc ggggtttaca atgtgctcat caaccaggtc 3120 aacgaactaa tgccagactt cattaagaat ggccacagtt tcccacaatc cctggccctg 3180 tccacgttgc agttcctctc cgtttgcaag tcggccaatc tgccgggatt cagtcctgct 3240 ctaagtccac ccaagcctcc aaagcaatgt gtgactctat ctgctggtct gccgcatttc 3300 tcaacgggct atatgcggtg ctggggccgt gataccttca tcgctctgcg tggctccatg 3360 ttcctcactg gccgttacaa cgaggctcgc ttcatcatca ttggatttgg tcagaccctt 3420 cgacacggac tcattccgaa tcttttggac agcggcagca agccgagatt caactgccgc 3480 gatgctatct ggtggtggat gtactgcatc aagcagtatg tggaggatgc ccccaagggt 3540 gccgagatcc tgaaggacaa ggtgtcccgc atatttccgt acgacgatgc cgatgcccat 3600 gctccaggtg ccttcgacca acttctcttc gacgtgatgc aggaggcact gcaggtgcat 3660 tttcagggct tgcagtatag ggagcgcaat gcaggctatg agatcgatgc gcacatggtg 3720 gaccagggct ttaacaatca gatcggaatt cacccggaga ctggctttgt attcggaggc 3780 aataacttca actgcggcac ttggatggac aaaatgggat cctcacagaa ggccggaaac 3840 aagggacgtc caagtacgcc gcgcgacgga tcagccgtgg agctcgttgg cctccagtat 3900 gccgtactcc ggtttatgca aagcctagcc gaaaaggagg ttatcccgta caccggcgtg 3960 gaacgaaagg gtccatcggg cgaagtgacc aagtggagct acaaggagtg ggcggatcgc 4020 atcaagaaca actttgacaa gtatttcttt gtatccgaat cggaaacctg ctcggtggcc 4080 aacaagaagc ttatctacaa ggacagctat ggagccaccc agagttggac ggactaccag 4140 ctgcgatgca acttccccat caccttgacc gtggctcccg acctgtgcaa tcctcagaat 4200 gcctggcgtg cactggagcg cgccaaaaag tatcttctgg gaccgctggg catgaagacg 4260 atggatcccg aggactggaa ctatagggcc aactatgaca actcaaatga ctccaccgat 4320 tgcactgtag cccatggcgc aaactaccac caggggccgg agtgggtatg gcccatcggt 4380 ttttacctgc gggcgcgcct gatcttcgcc aaaaagtgtg gccatttgga cgagaccatt 4440 gccgagacct gggccatact acgggcccat ctccgagagc tacagacatc ccattggcgc 4500 ggattgcccg agttgaccaa cgataatggc tcctactgcg gtgactcctg tcgcacgcag 4560 gcctggagtg ttgctgccat tttggaagtc ctgtacgatc tgcactcctt gggagcagac 4620 gtggcctaa 4629 <210> 7 <211> 1629 <212> PRT <213> Drosophila sp. <400> 7 Met Arg Tyr Gln Leu Phe Arg Trp Leu Tyr Gly Leu Ile Ala Thr Val   1 5 10 15 Asp Asn Glu Pro Leu Pro Leu Gln Ile Lys Ser Glu Glu Glu Ala Phe              20 25 30 Gly Glu Asn Lys Lys Lys Lys Gln Leu Ala Ser Leu Glu Asn Ala Ile          35 40 45 Ser Pro Gly Lys Leu Asp Ser Val Ala Ile Arg Thr Val Ser Ser Ala      50 55 60 Asn Ala Asn Ala Gly Asn Ala Gly Ser Ala Glu Ile Val Ser Asn  65 70 75 80 Gln Ile Ile Arg Arg Arg Glu Met Ser Thr Met Gly Lys Glu Thr Glu                  85 90 95 Ser His Ser Ile Ser Ser Glu Gly Gln Asp Ala Glu His Ile Leu             100 105 110 Tyr Arg Leu Lys Arg Gly Ser Lys Leu Ser Val His Pro Asp Ala Ser         115 120 125 Leu Leu Gly Arg Lys Ile Val Leu Tyr Thr Asn Tyr Pro Ala Glu Gly     130 135 140 Gln Lys Phe Val Arg Thr Glu Tyr Arg Val Leu Gly Trp Gln Leu Ser 145 150 155 160 Asn Gly Lys Gln Ile Thr Ser Val Met His Pro Glu Ala His Val Val                 165 170 175 Asp Thr Asp Ile Arg Ser Gln Val Glu Leu Asn Met Ser Gly Thr Tyr             180 185 190 His Phe Tyr Phe Arg Tyr Leu Glu Arg Pro Asp Thr Gly Cys Ser Gly         195 200 205 Ala Asp Gly Ala Leu Tyr Val Gln Val Glu Pro Thr Leu His Val Gly     210 215 220 Pro Pro Gly Ala Gln Lys Thr Ile Pro Leu Asp Ser Val Arg Cys Gln 225 230 235 240 Thr Val Leu Ala Lys Leu Leu Gly Pro Leu Asp Thr Trp Glu Pro Lys                 245 250 255 Leu Arg Val Ala Lys Glu Ala Gly Tyr Asn Val Ile His Phe Thr Pro             260 265 270 Ile Gln Glu Leu Gly Gly Ser Arg Ser Ser Cys Tyr Ser Leu Arg Asp Gln         275 280 285 Leu Lys Val Asn Ser His Phe Ala Pro Gln Lys Gly Gly Lys Ile Ser     290 295 300 Phe Glu Asp Val Glu Lys Val Ile Lys Lys Cys Arg Gln Glu Trp Gly 305 310 315 320 Val Ala Ser Ile Cys Asp Ile Val Leu Asn His Thr Ala Asn Glu Ser                 325 330 335 Asp Trp Leu Leu Gln His Pro Asp Ala Thr Tyr Ser Cys Ala Thr Cys             340 345 350 Pro Tyr Leu Arg Pro Ala Phe Leu Leu Asp Ala Thr Phe Ala Gln Cys         355 360 365 Gly Ala Asp Ile Ala Glu Gly Ser Leu Glu His Val Gly Val Pro Ala     370 375 380 Val Ile Glu Gln Glu Cys His Leu Glu Ala Leu Lys Tyr Gln Leu His 385 390 395 400 Thr Ser Tyr Met Ser Lys Val Asn Ile His Glu Leu Tyr Gln Cys Asp                 405 410 415 Val Met Lys Tyr Val Asn Glu Phe Met Ser Gln Val Arg Thr Arg Glu             420 425 430 Pro Pro Lys Asn Val Ala Asn Glu Cys Arg Phe Gln Glu Ile Gln Leu         435 440 445 Ile Gln Asp Pro Gln Tyr Arg Arg Leu Ala Ser Thr Ile Asn Phe Glu     450 455 460 Leu Ala Leu Glu Ile Phe Asn Ala Phe His Gly Asp Cys Phe Asp Glu 465 470 475 480 Glu Ser Arg Phe Arg Lys Cys Ala Glu Thr Leu Arg Arg His Leu Asp                 485 490 495 Ala Leu Asn Asp Arg Val Cys Glu Val Gln Gly Tyr Ile Asn Tyr             500 505 510 Ala Ile Asp Asn Val Leu Ala Gly Val Arg Tyr Glu Arg Val Gln Gly         515 520 525 Asp Gly Pro Arg Val Lys Glu Ile Ser Glu Lys His Ser Val Phe Met     530 535 540 Val Tyr Phe Thr His Thr Gly Thr Gln Gly Lys Ser Leu Thr Glu Ile 545 550 555 560 Glu Ala Asp Met Tyr Thr Lys Ala Gly Glu Phe Phe Met Ala His His                 565 570 575 Gly Trp Val Met Gly Tyr Ser Asp Pro Leu Arg Asp Phe Ala Glu Glu             580 585 590 Gln Pro Gly Arg Ala Asn Val Tyr Leu Lys Arg Glu Leu Ile Ser Trp         595 600 605 Gly Asp Ser Val Lys Leu Arg Phe Gly Arg Arg Pro Glu Asp Ser Pro     610 615 620 Tyr Leu Trp Gln His Met Thr Glu Tyr Val Gln Thr Thr Ala Arg Ile 625 630 635 640 Phe Asp Gly Val Arg Leu Asp Asn Cys His Ser Thr Pro Leu His Val                 645 650 655 Ala Glu Tyr Leu Leu Asp Ala Ala Arg Lys Ile Asn Pro Glu Leu Tyr             660 665 670 Val Val Ala Glu Leu Phe Thr Asn Ser Asp Tyr Thr Asp Asn Val Phe         675 680 685 Val Asn Arg Leu Gly Ile Thr Ser Leu Ile Arg Glu Ala Leu Ser Ala     690 695 700 Trp Asp Ser His Glu Gln Gly Arg Leu Val Tyr Arg Tyr Gly Gly Val 705 710 715 720 Pro Val Gly Gly Phe Gln Ala Asn Ser Ser Arg His Glu Ala Thr Ser                 725 730 735 Val Ala His Ala Leu Phe Leu Asp Leu Thr His Asp Asn Pro Ser Pro             740 745 750 Val Glu Lys Arg Ser Val Tyr Asp Leu Leu Ser Ser Ala Leu Val         755 760 765 Ser Met Ala Cys Cys Ala Thr Gly Ser Asn Arg Gly Tyr Asp Glu Leu     770 775 780 Val Pro His His Ile His Val Val Asp Glu Glu Arg Thr Tyr Gln Glu 785 790 795 800 Trp Gly Lys Gly Val Asp Ser Lys Ser Gly Ile Met Gly Ala Lys Arg                 805 810 815 Ala Leu Asn Leu Leu His Gly Gln Leu Ala Glu Glu Gly Phe Ser Gln             820 825 830 Val Tyr Val Asp Gln Met Asp Pro Asn Val Val Ala Val Thr Arg His         835 840 845 Ser Pro Ile Thr His Gln Ser Val Ile Leu Val Ala His Thr Ala Phe     850 855 860 Gly Tyr Pro Ser Pro Asn Ala Gly Pro Thr Gly Ile Arg Pro Leu Arg 865 870 875 880 Phe Glu Gly Val Leu Asp Glu Ile Ile Leu Glu Ala Ser Leu Thr Met                 885 890 895 Gln Ser Asp Lys Pro Phe Asp Arg Pro Ala Pro Phe Lys Lys Asp Pro             900 905 910 Asn Val Ile Asn Gly Phe Thr Gln Phe Gln Leu Asn Leu Gln Glu His         915 920 925 Ile Pro Leu Ala Lys Ser Thr Val Phe Gln Thr Gln Ala Tyr Ser Asp     930 935 940 Gly Asn Asn Thr Glu Leu Asn Phe Ala Asn Leu Arg Pro Gly Thr Val 945 950 955 960 Val Ala Ile Arg Val Ser Met His Pro Gly Pro Arg Thr Ser Phe Asp                 965 970 975 Lys Leu Gln Lys Ile Ser Ala Ala Leu Arg Ile Gly Ser Gly Glu Glu             980 985 990 Tyr Ser Gln Leu Gln Ala Ile Val Ser Lys Leu Asp Leu Val Ala Leu         995 1000 1005 Ser Gly Ala Leu Phe Ser Cys Asp Asp Glu Glu Arg Asp Leu Gly Lys    1010 1015 1020 Gly Gly Thr Ala Tyr Asp Ile Pro Asn Phe Gly Lys Ile Val Tyr Cys 1025 1030 1035 1040 Gly Leu Gln Gly Phe Ile Ser Leu Leu Thr Glu Ile Ser Pro Lys Asn                1045 1050 1055 Asp Leu Gly His Pro Leu Cys Asn Asn Leu Arg Asp Gly Asn Trp Met            1060 1065 1070 Met Asp Tyr Ile Ser Asp Arg Leu Thr Ser Tyr Glu Asp Leu Lys Pro        1075 1080 1085 Leu Ser Ala Trp Phe Lys Ala Thr Phe Glu Pro Leu Lys Asn Ile Pro    1090 1095 1100 Arg Tyr Leu Ile Pro Cys Tyr Phe Asp Ala Ile Val Ser Gly Val Tyr 1105 1110 1115 1120 Asn Val Leu Ile Asn Gln Val Asn Glu Leu Met Pro Asp Phe Ile Lys                1125 1130 1135 Asn Gly His Ser Phe Pro Gln Ser Leu Ala Leu Ser Thr Leu Gln Phe            1140 1145 1150 Leu Ser Val Cys Lys Ser Ala Asn Leu Pro Gly Phe Ser Pro Ala Leu        1155 1160 1165 Ser Pro Pro Lys Pro Pro Lys Gln Cys Val Thr Leu Ser Ala Gly Leu    1170 1175 1180 Pro His Phe Ser Thr Gly Tyr Met Arg Cys Trp Gly Arg Asp Thr Phe 1185 1190 1195 1200 Ile Ala Leu Arg Gly Ser Met Phe Leu Thr Gly Arg Tyr Asn Glu Ala                1205 1210 1215 Arg Phe Ile Ile Ile Gly Phe Gly Gln Thr Leu Arg His Gly Leu Ile            1220 1225 1230 Pro Asn Leu Leu Asp Ser Gly Ser Lys Pro Arg Phe Asn Cys Arg Asp        1235 1240 1245 Ala Ile Trp Trp Trp Met Tyr Cys Ile Lys Gln Tyr Val Glu Asp Ala    1250 1255 1260 Pro Lys Gly Ala Glu Ile Leu Lys Asp Lys Val Ser Arg Ile Phe Pro 1265 1270 1275 1280 Tyr Asp Asp Ala Asp Ala His Ala Pro Gly Ala Phe Asp Gln Leu Leu                1285 1290 1295 Phe Asp Val Met Gln Glu Ala Leu Gln Val His Phe Gln Gly Leu Gln            1300 1305 1310 Tyr Arg Glu Arg Asn Ala Gly Tyr Glu Ile Asp Ala His Met Val Asp        1315 1320 1325 Gln Gly Phe Asn Asn Gln Ile Gly Ile His Pro Glu Thr Gly Phe Val    1330 1335 1340 Phe Gly Gly Asn Asn Phe Asn Cys Gly Thr Trp Met Asp Lys Met Gly 1345 1350 1355 1360 Ser Ser Gln Lys Ala Gly Asn Lys Gly Arg Pro Ser Thr Pro Arg Asp                1365 1370 1375 Gly Ser Ala Val Glu Leu Val Gly Leu Gln Tyr Ala Val Leu Arg Phe            1380 1385 1390 Met Gln Ser Leu Ala Glu Lys Glu Val Ile Pro Tyr Thr Gly Val Glu        1395 1400 1405 Arg Lys Gly Pro Ser Gly Glu Val Thr Lys Trp Ser Tyr Lys Glu Trp    1410 1415 1420 Ala Asp Arg Ile Lys Asn Asn Phe Asp Lys Tyr Phe Phe Val Ser Glu 1425 1430 1435 1440 Ser Glu Thr Cys Ser Val Ala Asn Lys Lys Leu Ile Tyr Lys Asp Ser                1445 1450 1455 Tyr Gly Ala Thr Gln Ser Trp Thr Asp Tyr Gln Leu Arg Cys Asn Phe            1460 1465 1470 Pro Ile Thr Leu Thr Val Ala Pro Asp Leu Cys Asn Pro Gln Asn Ala        1475 1480 1485 Trp Arg Ala Leu Glu Arg Ala Lys Lys Tyr Leu Leu Gly Pro Leu Gly    1490 1495 1500 Met Lys Thr Met Asp Pro Glu Asp Trp Asn Tyr Arg Ala Asn Tyr Asp 1505 1510 1515 1520 Asn Ser Asn Asp Ser Thr Asp Cys Thr Val Ala His Gly Ala Asn Tyr                1525 1530 1535 His Gln Gly Pro Glu Trp Val Trp Pro Ile Gly Phe Tyr Leu Arg Ala            1540 1545 1550 Arg Leu Ile Phe Ala Lys Lys Cys Gly His Leu Asp Glu Thr Ile Ala        1555 1560 1565 Glu Thr Trp Ala Ile Leu Arg Ala His Leu Arg Glu Leu Gln Thr Ser    1570 1575 1580 His Trp Arg Gly Leu Pro Glu Leu Thr Asn Asp Asn Gly Ser Tyr Cys 1585 1590 1595 1600 Gly Asp Ser Cys Arg Thr Gln Ala Trp Ser Val Ala Ile Leu Glu                1605 1610 1615 Val Leu Tyr Asp Leu His Ser Leu Gly Ala Asp Val Ala            1620 1625 <210> 8 <211> 1542 <212> PRT <213> Drosophila sp. <400> 8 Met Ser Thr Met Gly Lys Glu Thr Glu Ser His Ser Ile Pro Ile Ser   1 5 10 15 Glu Gly Gln Asp Ala Glu His Ile Leu Tyr Arg Leu Lys Arg Gly Ser              20 25 30 Lys Leu Ser Val His Pro Asp Ala Ser Leu Leu Gly Arg Lys Ile Val          35 40 45 Leu Tyr Thr Asn Tyr Pro Ala Glu Gly Gln Lys Phe Val Arg Thr Glu      50 55 60 Tyr Arg Val Leu Gly Trp Gln Leu Ser Asn Gly Lys Gln Ile Thr Ser  65 70 75 80 Val Met His Pro Glu Ala His Val Val Asp Thr Asp Ile Arg Ser Gln                  85 90 95 Val Glu Leu Asn Met Ser Gly Thr Tyr His Phe Tyr Phe Arg Tyr Leu             100 105 110 Glu Arg Pro Asp Thr Gly Cys Ser Gly Ala Asp Gly Ala Leu Tyr Val         115 120 125 Gln Val Glu Pro Thr Leu His Val Gly Pro Pro Gly Ala Gln Lys Thr     130 135 140 Ile Pro Leu Asp Ser Val Arg Cys Gln Thr Val Leu Ala Lys Leu Leu 145 150 155 160 Gly Pro Leu Asp Thr Trp Glu Pro Lys Leu Arg Val Ala Lys Glu Ala                 165 170 175 Gly Tyr Asn Val Ile His Phe Thr Pro Ile Gln Glu Leu Gly Gly Ser             180 185 190 Arg Ser Cys Tyr Ser Leu Arg Asp Gln Leu Lys Val Asn Ser His Phe         195 200 205 Ala Pro Gln Lys Gly Gly Lys Ile Ser Phe Glu Asp Val Glu Lys Val     210 215 220 Ile Lys Lys Cys Arg Gln Glu Trp Gly Val Ala Ser Ile Cys Asp Ile 225 230 235 240 Val Leu Asn His Thr Ala Asn Glu Ser Asp Trp Leu Leu Gln His Pro                 245 250 255 Asp Ala Thr Tyr Ser Cys Ala Thr Cys Pro Tyr Leu Arg Pro Ala Phe             260 265 270 Leu Leu Asp Ala Thr Phe Ala Gln Cys Gly Ala Asp Ile Ala Glu Gly         275 280 285 Ser Leu Glu His Val Gly Val Pro Ala Val Ile Glu Gln Glu Cys His     290 295 300 Leu Glu Ala Leu Lys Tyr Gln Leu His Thr Ser Tyr Met Ser Lys Val 305 310 315 320 Asn Ile His Glu Leu Tyr Gln Cys Asp Val Met Lys Tyr Val Asn Glu                 325 330 335 Phe Met Ser Gln Val Arg Thr Arg Glu Pro Pro Lys Asn Val Ala Asn             340 345 350 Glu Cys Arg Phe Gln Glu Ile Gln Leu Ile Gln Asp Pro Gln Tyr Arg         355 360 365 Arg Leu Ala Ser Thr Ile Asn Phe Glu Leu Ala Leu Glu Ile Phe Asn     370 375 380 Ala Phe His Gly Asp Cys Phe Asp Glu Glu Ser Arg Phe Arg Lys Cys 385 390 395 400 Ala Glu Thr Leu Arg Arg His Leu Asp Ala Leu Asn Asp Arg Val Arg                 405 410 415 Cys Glu Val Gln Gly Tyr Ile Asn Tyr Ala Ile Asp Asn Val Leu Ala             420 425 430 Gly Val Arg Tyr Glu Arg Val Gln Gly Asp Gly Pro Arg Val Lys Glu         435 440 445 Ile Ser Glu Lys His Ser Val Phe Met Val Tyr Phe Thr His Thr Gly     450 455 460 Thr Gln Gly Lys Ser Leu Thr Glu Ile Glu Ala Asp Met Tyr Thr Lys 465 470 475 480 Ala Gly Glu Phe Phe Met Ala His His Gly Trp Val Met Gly Tyr Ser                 485 490 495 Asp Pro Leu Arg Asp Phe Ala Glu Glu Gln Pro Gly Arg Ala Asn Val             500 505 510 Tyr Leu Lys Arg Glu Leu Ile Ser Trp Gly Asp Ser Val Lys Leu Arg         515 520 525 Phe Gly Arg Arg Pro Glu Asp Ser Pro Tyr Leu Trp Gln His Met Thr     530 535 540 Glu Tyr Val Gln Thr Thr Ala Arg Ile Phe Asp Gly Val Arg Leu Asp 545 550 555 560 Asn Cys His Ser Thr Pro Leu His Val Ala Glu Tyr Leu Leu Asp Ala                 565 570 575 Ala Arg Lys Ile Asn Pro Glu Leu Tyr Val Val Ala Glu Leu Phe Thr             580 585 590 Asn Ser Asp Tyr Thr Asp Asn Val Phe Val Asn Arg Leu Gly Ile Thr         595 600 605 Ser Leu Ile Arg Glu Ala Leu Ser Ala Trp Asp Ser His Glu Gln Gly     610 615 620 Arg Leu Val Tyr Arg Tyr Gly Gly Val Val Gly Gly Phe Gln Ala 625 630 635 640 Asn Ser Ser Arg His Glu Ala Thr Ser Val Ala His Ala Leu Phe Leu                 645 650 655 Asp Leu Thr His Asp Asn Pro Ser Pro Val Glu Lys Arg Ser Val Tyr             660 665 670 Asp Leu Leu Pro Ser Ala Leu Val Ser Ala Cys Cys Ala Thr         675 680 685 Gly Ser Asn Arg Gly Tyr Asp Glu Leu Val Pro His His Ile His Val     690 695 700 Val Asp Glu Glu Arg Thr Tyr Gln Glu Trp Gly Lys Gly Val Asp Ser 705 710 715 720 Lys Ser Gly Ile Met Gly Ala Lys Arg Ala Leu Asn Leu Leu His Gly                 725 730 735 Gln Leu Ala Glu Glu Gly Phe Ser Gln Val Tyr Val Asp Gln Met Asp             740 745 750 Pro Asn Val Ala Val Thr Arg His Ser Pro Ile Thr His Gln Ser         755 760 765 Val Ile Leu Val Ala His Thr Ala Phe Gly Tyr Pro Ser Pro Asn Ala     770 775 780 Gly Pro Thr Gly Ile Arg Pro Leu Arg Phe Glu Gly Val Leu Asp Glu 785 790 795 800 Ile Ile Leu Glu Ala Ser Leu Thr Met Gln Ser Asp Lys Pro Phe Asp                 805 810 815 Arg Pro Ala Pro Phe Lys Lys Asp Pro Asn Val Ile Asn Gly Phe Thr             820 825 830 Gln Phe Gln Leu Asn Leu Gln Glu His Ile Pro Leu Ala Lys Ser Thr         835 840 845 Val Phe Gln Thr Gln Ala Tyr Ser Asp Gly Asn Asn Thr Glu Leu Asn     850 855 860 Phe Ala Asn Leu Arg Pro Gly Thr Val Val Ala Ile Arg Val Ser Met 865 870 875 880 His Pro Gly Pro Arg Thr Ser Phe Asp Lys Leu Gln Lys Ile Ser Ala                 885 890 895 Ala Leu Arg Ile Gly Ser Gly Glu Glu Tyr Ser Gln Leu Gln Ala Ile             900 905 910 Val Ser Lys Leu Asp Leu Val Ala Leu Ser Gly Ala Leu Phe Ser Cys         915 920 925 Asp Asp Glu Glu Arg Asp Leu Gly Lys Gly Gly Thr Ala Tyr Asp Ile     930 935 940 Pro Asn Phe Gly Lys Ile Val Tyr Cys Gly Leu Gln Gly Phe Ile Ser 945 950 955 960 Leu Leu Thr Glu Ile Ser Pro Lys Asn Asp Leu Gly His Pro Leu Cys                 965 970 975 Asn Asn Leu Arg Asp Gly Asn Trp Met Met Asp Tyr Ile Ser Asp Arg             980 985 990 Leu Thr Ser Tyr Glu Asp Leu Lys Pro Leu Ser Ala Trp Phe Lys Ala         995 1000 1005 Thr Phe Glu Pro Leu Lys Asn Ile Pro Arg Tyr Leu Ile Pro Cys Tyr    1010 1015 1020 Phe Asp Ala Ile Val Ser Gly Val Tyr Asn Val Leu Ile Asn Gln Val 1025 1030 1035 1040 Asn Glu Leu Met Pro Asp Phe Ile Lys Asn Gly His Ser Phe Pro Gln                1045 1050 1055 Ser Leu Ala Leu Ser Thr Leu Gln Phe Leu Ser Val Cys Lys Ser Ala            1060 1065 1070 Asn Leu Pro Gly Phe Ser Pro Ala Leu Ser Pro Pro Lys Pro Pro Lys        1075 1080 1085 Gln Cys Val Thr Leu Ser Ala Gly Leu Pro His Phe Ser Thr Gly Tyr    1090 1095 1100 Met Arg Cys Trp Gly Arg Asp Thr Phe Ile Ala Leu Arg Gly Ser Met 1105 1110 1115 1120 Phe Leu Thr Gly Arg Tyr Asn Gly Ala Arg Phe Ile Ile Ile Gly Phe                1125 1130 1135 Gly Gln Thr Leu Arg His Gly Leu Ile Pro Asn Leu Leu Asp Ser Gly            1140 1145 1150 Ser Lys Pro Arg Phe Asn Cys Arg Asp Ala Ile Trp Trp Trp Met Tyr        1155 1160 1165 Cys Ile Lys Gln Tyr Val Glu Asp Ala Pro Lys Gly Ala Glu Ile Leu    1170 1175 1180 Lys Asp Lys Val Ser Arg Ile Phe Pro Tyr Asp Asp Ala Asp Ala His 1185 1190 1195 1200 Ala Pro Gly Ala Phe Asp Gln Leu Leu Phe Asp Val Met Gln Glu Ala                1205 1210 1215 Leu Gln Val His Phe Gln Gly Leu Gln Tyr Arg Glu Arg Asn Ala Gly            1220 1225 1230 Tyr Glu Ile Asp Ala His Met Val Asp Gln Gly Phe Asn Asn Gln Ile        1235 1240 1245 Gly Ile His Pro Glu Thr Gly Phe Val Phe Gly Gly Asn Asn Phe Asn    1250 1255 1260 Cys Gly Thr Trp Met Asp Lys Met Gly Ser Ser Gln Lys Ala Gly Asn 1265 1270 1275 1280 Lys Gly Arg Pro Ser Thr Pro Arg Asp Gly Ser Ala Val Glu Leu Val                1285 1290 1295 Gly Leu Gln Tyr Ala Val Leu Arg Phe Met Gln Ser Leu Ala Glu Lys            1300 1305 1310 Glu Val Ile Pro Tyr Thr Gly Val Glu Arg Lys Gly Pro Ser Gly Glu        1315 1320 1325 Val Thr Lys Trp Ser Tyr Lys Glu Trp Ala Asp Arg Ile Lys Asn Asn    1330 1335 1340 Phe Asp Lys Tyr Phe Phe Val Ser Glu Ser Glu Thr Cys Ser Val Ala 1345 1350 1355 1360 Asn Lys Lys Leu Ile Tyr Lys Asp Ser Tyr Gly Ala Thr Gln Ser Trp                1365 1370 1375 Thr Asp Tyr Gln Leu Arg Cys Asn Phe Pro Ile Thr Leu Thr Val Ala            1380 1385 1390 Pro Asp Leu Cys Asn Pro Gln Asn Ala Trp Arg Ala Leu Glu Arg Ala        1395 1400 1405 Lys Lys Tyr Leu Leu Gly Pro Leu Gly Met Lys Thr Met Asp Pro Glu    1410 1415 1420 Asp Trp Asn Tyr Arg Ala Asn Tyr Asp Asn Ser Asn Asp Ser Thr Asp 1425 1430 1435 1440 Cys Thr Val Ala His Gly Ala Asn Tyr His Gln Gly Pro Glu Trp Val                1445 1450 1455 Trp Pro Ile Gly Phe Tyr Leu Arg Ala Arg Leu Ile Phe Ala Lys Lys            1460 1465 1470 Cys Gly His Leu Asp Glu Thr Ile Ala Glu Thr Trp Ala Ile Leu Arg        1475 1480 1485 Ala His Leu Arg Glu Leu Gln Thr Ser His Trp Arg Gly Leu Pro Glu    1490 1495 1500 Leu Thr Asn Asp Asn Gly Ser Tyr Cys Gly Asp Ser Cys Arg Thr Gln 1505 1510 1515 1520 Ala Trp Ser Val Ala Ile Leu Glu Val Leu Tyr Asp Leu His Ser                1525 1530 1535 Leu Gly Ala Asp Val Ala            1540 <210> 9 <211> 1546 <212> PRT <213> Drosophila sp. <400> 9 Met Pro Leu Ala Met Ser Thr Met Gly Lys Glu Thr Glu Ser His Ser   1 5 10 15 Ile Pro Ile Ser Glu Gly Gln Asp Ala Glu His Ile Leu Tyr Arg Leu              20 25 30 Lys Arg Gly Ser Lys Leu Ser Val His Pro Asp Ala Ser Leu Leu Gly          35 40 45 Arg Lys Ile Val Leu Tyr Thr Asn Tyr Pro Ala Glu Gly Gln Lys Phe      50 55 60 Val Arg Thr Glu Tyr Arg Val Leu Gly Trp Gln Leu Ser Asn Gly Lys  65 70 75 80 Gln Ile Thr Ser Val Met His Pro Glu Ala His Val Val Asp Thr Asp                  85 90 95 Ile Arg Ser Gln Val Glu Leu Asn Met Ser Gly Thr Tyr His Phe Tyr             100 105 110 Phe Arg Tyr Leu Glu Arg Pro Asp Thr Gly Cys Ser Gly Ala Asp Gly         115 120 125 Ala Leu Tyr Val Gln Val Glu Pro Thr Leu His Val Gly Pro Pro Gly     130 135 140 Ala Gln Lys Thr Ile Pro Leu Asp Ser Val Arg Cys Gln Thr Val Leu 145 150 155 160 Ala Lys Leu Leu Gly Pro Leu Asp Thr Trp Glu Pro Lys Leu Arg Val                 165 170 175 Ala Lys Glu Ala Gly Tyr Asn Val Ile His Phe Thr Pro Ile Gln Glu             180 185 190 Leu Gly Gly Ser Ser Ser Cys Tyr Ser Leu Arg Asp Gln Leu Lys Val         195 200 205 Asn Ser His Phe Ala Pro Gln Lys Gly Gly Lys Ile Ser Phe Glu Asp     210 215 220 Val Glu Lys Val Ile Lys Lys Cys Arg Gln Glu Trp Gly Val Ala Ser 225 230 235 240 Ile Cys Asp Ile Val Leu Asn His Thr Ala Asn Glu Ser Asp Trp Leu                 245 250 255 Leu Gln His Pro Asp Ala Thr Tyr Ser Cys Ala Thr Cys Pro Tyr Leu             260 265 270 Arg Pro Ala Phe Leu Leu Asp Ala Thr Phe Ala Gln Cys Gly Ala Asp         275 280 285 Ile Ala Glu Gly Ser Leu Glu His Val Gly Val Pro Ala Val Ile Glu     290 295 300 Gln Glu Cys His Leu Glu Ala Leu Lys Tyr Gln Leu His Thr Ser Tyr 305 310 315 320 Met Ser Lys Val Asn Ile His Glu Leu Tyr Gln Cys Asp Val Met Lys                 325 330 335 Tyr Val Asn Glu Phe Met Ser Gln Val Arg Thr Arg Glu Pro Pro Lys             340 345 350 Asn Val Ala Asn Glu Cys Arg Phe Gln Glu Ile Gln Leu Ile Gln Asp         355 360 365 Pro Gln Tyr Arg Arg Leu Ala Ser Thr Ile Asn Phe Glu Leu Ala Leu     370 375 380 Glu Ile Phe Asn Ala Phe His Gly Asp Cys Phe Asp Glu Glu Ser Arg 385 390 395 400 Phe Arg Lys Cys Ala Glu Thr Leu Arg Arg His Leu Asp Ala Leu Asn                 405 410 415 Asp Arg Val Cys Glu Val Gln Gly Tyr Ile Asn Tyr Ala Ile Asp             420 425 430 Asn Val Leu Ala Gly Val Arg Tyr Glu Arg Val Gln Gly Asp Gly Pro         435 440 445 Arg Val Lys Glu Ile Ser Glu Lys His Ser Val Phe Met Val Tyr Phe     450 455 460 Thr His Thr Gly Thr Gln Gly Lys Ser Leu Thr Glu Ile Glu Ala Asp 465 470 475 480 Met Tyr Thr Lys Ala Gly Glu Phe Phe Met Ala His His Gly Trp Val                 485 490 495 Met Gly Tyr Ser Asp Pro Leu Arg Asp Phe Ala Glu Glu Gln Pro Gly             500 505 510 Arg Ala Asn Val Tyr Leu Lys Arg Glu Leu Ile Ser Trp Gly Asp Ser         515 520 525 Val Lys Leu Arg Phe Gly Arg Arg Pro Glu Asp Ser Pro Tyr Leu Trp     530 535 540 Gln His Met Thr Glu Tyr Val Gln Thr Thr Ala Arg Ile Phe Asp Gly 545 550 555 560 Val Arg Leu Asp Asn Cys His Ser Thr Pro Leu His Val Ala Glu Tyr                 565 570 575 Leu Leu Asp Ala Ala Arg Lys Asle Pro Glu Leu Tyr Val Val Ala             580 585 590 Glu Leu Phe Thr Asn Ser Asp Tyr Thr Asp Asn Val Phe Val Asn Arg         595 600 605 Leu Gly Ile Thr Ser Leu Ile Arg Glu Ala Leu Ser Ala Trp Asp Ser     610 615 620 His Glu Gln Gly Arg Leu Val Tyr Arg Tyr Gly Gly Val Pro Val Gly 625 630 635 640 Gly Phe Gln Ala Asn Ser Ser Arg His Glu Ala Thr Ser Val Ala His                 645 650 655 Ala Leu Phe Leu Asp Leu Thr His Asp Asn Pro Ser Pro Val Glu Lys             660 665 670 Arg Ser Val Tyr Asp Leu Leu Ser Ser Ala Leu Val Ser Ala         675 680 685 Cys Cys Ala Thr Gly Ser Asn Arg Gly Tyr Asp Glu Leu Val Pro His     690 695 700 His Ile His Val Val Asp Glu Glu Arg Thr Tyr Gln Glu Trp Gly Lys 705 710 715 720 Gly Val Asp Ser Lys Ser Gly Ile Met Gly Ala Lys Arg Ala Leu Asn                 725 730 735 Leu Leu His Gly Gln Leu Ala Glu Glu Gly Phe Ser Gln Val Tyr Val             740 745 750 Asp Gln Met Asp Pro Asn Val Val Ala Val Thr Arg His Ser Pro Ile         755 760 765 Thr His Gln Ser Val Ile Leu Val Ala His Thr Ala Phe Gly Tyr Pro     770 775 780 Ser Pro Asn Ala Gly Pro Thr Gly Ile Arg Pro Leu Arg Phe Glu Gly 785 790 795 800 Val Leu Asp Glu Ile Ile Leu Glu Ala Ser Leu Thr Met Gln Ser Asp                 805 810 815 Lys Pro Phe Asp Arg Pro Ala Pro Phe Lys Lys Asp Pro Asn Val Ile             820 825 830 Asn Gly Phe Thr Gln Phe Gln Leu Asn Leu Gln Glu His Ile Pro Leu         835 840 845 Ala Lys Ser Thr Val Phe Gln Thr Gln Ala Tyr Ser Asp Gly Asn Asn     850 855 860 Thr Glu Leu Asn Phe Ala Asn Leu Arg Pro Gly Thr Val Val Ala Ile 865 870 875 880 Arg Val Ser Met Met Pro Gly Pro Arg Thr Ser Phe Asp Lys Leu Gln                 885 890 895 Lys Ile Ser Ala Leu Arg Ile Gly Ser Gly Glu Glu Tyr Ser Gln             900 905 910 Leu Gln Ala Ile Val Ser Lys Leu Asp Leu Val Ala Leu Ser Gly Ala         915 920 925 Leu Phe Ser Cys Asp Asp Glu Glu Arg Asp Leu Gly Lys Gly Gly Thr     930 935 940 Ala Tyr Asp Ile Pro Asn Phe Gly Lys Ile Val Tyr Cys Gly Leu Gln 945 950 955 960 Gly Phe Ile Ser Leu Leu Thr Glu Ile Ser Pro Lys Asn Asp Leu Gly                 965 970 975 His Pro Leu Cys Asn Asn Leu Arg Asp Gly Asn Trp Met Met Asp Tyr             980 985 990 Ile Ser Asp Arg Leu Thr Ser Tyr Glu Asp Leu Lys Pro Leu Ser Ala         995 1000 1005 Trp Phe Lys Ala Thr Phe Glu Pro Leu Lys Asn Ile Pro Arg Tyr Leu    1010 1015 1020 Ile Pro Cys Tyr Phe Asp Ala Ile Val Ser Gly Val Tyr Asn Val Leu 1025 1030 1035 1040 Ile Asn Gln Val Asn Glu Leu Met Pro Asp Phe Ile Lys Asn Gly His                1045 1050 1055 Ser Phe Pro Gln Ser Leu Ala Leu Ser Thr Leu Gln Phe Leu Ser Val            1060 1065 1070 Cys Lys Ser Ala Asn Leu Pro Gly Phe Ser Pro Ala Leu Ser Pro Pro        1075 1080 1085 Lys Pro Pro Lys Gln Cys Val Thr Leu Ser Ala Gly Leu Pro His Phe    1090 1095 1100 Ser Thr Gly Tyr Met Arg Cys Trp Gly Arg Asp Thr Phe Ile Ala Leu 1105 1110 1115 1120 Arg Gly Ser Met Phe Leu Thr Gly Arg Tyr Asn Glu Ala Arg Phe Ile                1125 1130 1135 Ile Ile Gly Phe Gly Gln Thr Leu Arg His Gly Leu Ile Pro Asn Leu            1140 1145 1150 Leu Asp Ser Gly Ser Lys Pro Arg Phe Asn Cys Arg Asp Ala Ile Trp        1155 1160 1165 Trp Trp Met Tyr Cys Ile Lys Gln Tyr Val Glu Asp Ala Pro Lys Gly    1170 1175 1180 Ala Glu Ile Leu Lys Asp Lys Val Ser Arg Ile Phe Pro Tyr Asp Asp 1185 1190 1195 1200 Ala Asp Ala His Ala Pro Gly Ala Phe Asp Gln Leu Leu Phe Asp Val                1205 1210 1215 Met Gln Glu Ala Leu Gln Val His Phe Gln Gly Leu Gln Tyr Arg Glu            1220 1225 1230 Arg Asn Ala Gly Tyr Glu Ile Asp Ala His Met Val Asp Gln Gly Phe        1235 1240 1245 Asn Asn Gln Ile Gly Ile His Pro Glu Thr Gly Phe Val Phe Gly Gly    1250 1255 1260 Asn Asn Phe Asn Cys Gly Thr Trp Met Asp Lys Met Gly Ser Ser Gln 1265 1270 1275 1280 Lys Ala Gly Asn Lys Gly Arg Pro Ser Thr Pro Arg Asp Gly Ser Ala                1285 1290 1295 Val Glu Leu Val Gly Leu Gln Tyr Ala Val Leu Arg Phe Met Gln Ser            1300 1305 1310 Leu Ala Glu Lys Glu Val Ile Pro Tyr Thr Gly Val Glu Arg Lys Gly        1315 1320 1325 Pro Ser Gly Glu Val Thr Lys Trp Ser Tyr Lys Glu Trp Ala Asp Arg    1330 1335 1340 Ile Lys Asn Asn Phe Asp Lys Tyr Phe Phe Val Ser Glu Ser Glu Thr 1345 1350 1355 1360 Cys Ser Val Ala Asn Lys Lys Leu Ile Tyr Lys Asp Ser Tyr Gly Ala                1365 1370 1375 Thr Gln Ser Trp Thr Asp Tyr Gln Leu Arg Cys Asn Phe Pro Ile Thr            1380 1385 1390 Leu Thr Val Ala Pro Asp Leu Cys Asn Pro Gln Asn Ala Trp Arg Ala        1395 1400 1405 Leu Glu Arg Ala Lys Lys Tyr Leu Leu Gly Pro Leu Gly Met Lys Thr    1410 1415 1420 Met Asp Pro Glu Asp Trp Asn Tyr Arg Ala Asn Tyr Asp Asn Ser Asn 1425 1430 1435 1440 Asp Ser Thr Asp Cys Thr Val Ala His Gly Ala Asn Tyr His Gln Gly                1445 1450 1455 Pro Glu Trp Val Trp Pro Ile Gly Phe Tyr Leu Arg Ala Arg Leu Ile            1460 1465 1470 Phe Ala Lys Lys Cys Gly His Leu Asp Glu Thr Ile Ala Glu Thr Trp        1475 1480 1485 Ala Ile Leu Arg Ala His Leu Arg Glu Leu Gln Thr Ser His Trp Arg    1490 1495 1500 Gly Leu Pro Glu Leu Thr Asn Asp Asn Gly Ser Tyr Cys Gly Asp Ser 1505 1510 1515 1520 Cys Arg Thr Gln Ala Trp Ser Val Ala Ile Leu Glu Val Leu Tyr                1525 1530 1535 Asp Leu His Ser Leu Gly Ala Asp Val Ala            1540 1545 <210> 10 <211> 1563 <212> PRT <213> Drosophila sp. <400> 10 Met Ser Thr Met Gly Lys Glu Thr Glu Ser His Ser Ile Pro Ile Ser   1 5 10 15 Glu Gly Gln Asp Ala Glu His Ile Leu Tyr Arg Leu Lys Arg Gly Ser              20 25 30 Lys Leu Ser Val His Pro Asp Ala Ser Leu Leu Gly Arg Lys Ile Val          35 40 45 Leu Tyr Thr Asn Tyr Pro Ala Glu Gly Gln Lys Phe Val Arg Thr Glu      50 55 60 Tyr Arg Val Leu Gly Trp Gln Leu Ser Asn Gly Lys Gln Ile Thr Ser  65 70 75 80 Val Met His Pro Glu Ala His Val Val Asp Thr Asp Ile Arg Ser Gln                  85 90 95 Val Glu Leu Asn Met Ser Gly Thr Tyr His Phe Tyr Phe Arg Tyr Leu             100 105 110 Glu Arg Phe Glu Thr Ile Leu Phe Arg Ile Asp Phe Ala Leu Ala Leu         115 120 125 Met Cys Val Asn Ile Phe Arg Pro Asp Thr Gly Cys Ser Gly Ala Asp     130 135 140 Gly Ala Leu Tyr Val Gln Val Glu Pro Thr Leu His Val Gly Pro Pro 145 150 155 160 Gly Ala Gln Lys Thr Ile Pro Leu Asp Ser Val Arg Cys Gln Thr Val                 165 170 175 Leu Ala Lys Leu Leu Gly Pro Leu Asp Thr Trp Glu Pro Lys Leu Arg             180 185 190 Val Ala Lys Glu Ala Gly Tyr Asn Val Ile His Phe Thr Pro Ile Gln         195 200 205 Glu Leu Gly Gly Ser Ser Arg Cys Tyr Ser Leu Arg Asp Gln Leu Lys     210 215 220 Val Asn Ser His Phe Ala Pro Gln Lys Gly Gly Lys Ile Ser Phe Glu 225 230 235 240 Asp Val Glu Lys Val Ile Lys Lys Cys Arg Gln Glu Trp Gly Val Ala                 245 250 255 Ser Ile Cys Asp Ile Val Leu Asn His Thr Ala Asn Glu Ser Asp Trp             260 265 270 Leu Leu Gln His Pro Asp Ala Thr Tyr Ser Cys Ala Thr Cys Pro Tyr         275 280 285 Leu Arg Pro Ala Phe Leu Leu Asp Ala Thr Phe Ala Gln Cys Gly Ala     290 295 300 Asp Ile Ala Glu Gly Ser Leu Glu His Val Gly Val Pro Ala Val Ile 305 310 315 320 Glu Gln Glu Cys His Leu Glu Ala Leu Lys Tyr Gln Leu His Thr Ser                 325 330 335 Tyr Met Ser Lys Val Asn Ile His Glu Leu Tyr Gln Cys Asp Val Met             340 345 350 Lys Tyr Val Asn Glu Phe Met Ser Gln Val Arg Thr Arg Glu Pro Pro         355 360 365 Lys Asn Val Ala Asn Glu Cys Arg Phe Gln Glu Ile Gln Leu Ile Gln     370 375 380 Asp Pro Gln Tyr Arg Arg Leu Ala Ser Thr Ile Asn Phe Glu Leu Ala 385 390 395 400 Leu Glu Ile Phe Asn Ala Phe His Gly Asp Cys Phe Asp Glu Glu Ser                 405 410 415 Arg Phe Arg Lys Cys Ala Glu Thr Leu Arg Arg His Leu Asp Ala Leu             420 425 430 Asn Asp Arg Val Cys Glu Val Gln Gly Tyr Ile Asn Tyr Ala Ile         435 440 445 Asp Asn Val Leu Ala Gly Val Arg Tyr Glu Arg Val Gln Gly Asp Gly     450 455 460 Pro Arg Val Lys Glu Ile Ser Glu Lys His Ser Val Phe Met Val Tyr 465 470 475 480 Phe Thr His Thr Gly Thr Gln Gly Lys Ser Leu Thr Glu Ile Glu Ala                 485 490 495 Asp Met Tyr Thr Lys Ala Gly Glu Phe Phe Met Ala His Asn Gly Trp             500 505 510 Val Met Gly Tyr Ser Asp Pro Leu Arg Asp Phe Ala Glu Glu Gln Pro         515 520 525 Gly Arg Ala Asn Val Tyr Leu Lys Arg Glu Leu Ile Ser Trp Gly Asp     530 535 540 Ser Val Lys Leu Arg Phe Gly Arg Arg Pro Glu Asp Ser Pro Tyr Leu 545 550 555 560 Trp Gln His Met Thr Glu Tyr Val Gln Thr Thr Ala Arg Ile Phe Asp                 565 570 575 Gly Val Arg Leu Asp Asn Cys His Ser Thr Pro Leu His Val Ala Glu             580 585 590 Tyr Leu Leu Asp Ala Ala Arg Lys Ile Asn Pro Glu Leu Tyr Val Val         595 600 605 Ala Glu Leu Phe Thr Asn Ser Asp Tyr Thr Asp Asn Val Phe Val Asn     610 615 620 Arg Leu Gly Ile Thr Ser Leu Ile Arg Glu Ala Leu Ser Ala Trp Asp 625 630 635 640 Ser His Glu Gln Gly Arg Leu Val Tyr Arg Tyr Gly Gly Val Val Val                 645 650 655 Gly Gly Phe Gln Ala Asn Ser Ser Arg His Glu Ala Thr Ser Val Ala             660 665 670 His Ala Leu Phe Leu Asp Leu Thr His Asp Asn Pro Ser Pro Val Glu         675 680 685 Lys Arg Ser Val Tyr Asp Leu Leu Ser Ser Ala Leu Val Ser Met     690 695 700 Ala Cys Cys Ala Thr Gly Ser Asn Arg Gly Tyr Asp Glu Leu Val Pro 705 710 715 720 His His Ile His Val Val Asp Glu Glu Arg Thr Tyr Gln Glu Trp Gly                 725 730 735 Lys Gly Val Asp Ser Lys Ser Gly Ile Met Gly Ala Lys Arg Ala Leu             740 745 750 Asn Leu Leu His Gly Gln Leu Ala Glu Glu Gly Phe Ser Gln Val Tyr         755 760 765 Val Asp Gln Met Asp Pro Asn Val Val Ala Val Thr Arg His Ser Pro     770 775 780 Ile Thr His Gln Ser Val Ile Leu Val Ala His Thr Ala Phe Gly Tyr 785 790 795 800 Pro Ser Pro Asn Ala Gly Pro Thr Gly Ile Arg Pro Leu Arg Phe Glu                 805 810 815 Gly Val Leu Asp Glu Ile Ile Leu Glu Ala Ser Leu Thr Met Gln Ser             820 825 830 Asp Lys Pro Phe Asp Arg Pro Ala Pro Phe Lys Lys Asp Pro Asn Val         835 840 845 Ile Asn Gly Phe Thr Gln Phe Gln Leu Asn Leu Gln Glu His Ile Pro     850 855 860 Leu Ala Lys Ser Thr Val Phe Gln Thr Gln Ala Tyr Ser Asp Gly Asn 865 870 875 880 Asn Thr Glu Leu Asn Phe Ala Asn Leu Arg Pro Gly Thr Val Val Ala                 885 890 895 Ile Arg Val Ser Met Met Pro Gly Pro Arg Thr Ser Phe Asp Lys Leu             900 905 910 Gln Lys Ile Ser Ala Ala Leu Arg Ile Gly Ser Gly Glu Glu Tyr Ser         915 920 925 Gln Leu Gln Ale Ile Val Ser Lys Leu Asp Leu Val Ala Leu Ser Gly     930 935 940 Ala Leu Phe Ser Cys Asp Asp Glu Glu Arg Asp Leu Gly Lys Gly Gly 945 950 955 960 Thr Ala Tyr Asp Ile Pro Asn Phe Gly Lys Ile Val Tyr Cys Gly Leu                 965 970 975 Gln Gly Phe Ile Ser Leu Leu Thr Glu Ile Ser Pro Lys Asn Asp Leu             980 985 990 Gly His Pro Leu Cys Asn Asn Leu Arg Asp Gly Asn Trp Met Met Asp         995 1000 1005 Tyr Ile Ser Asp Arg Leu Thr Ser Tyr Glu Asp Leu Lys Pro Leu Ser    1010 1015 1020 Ala Trp Phe Lys Ala Thr Phe Glu Pro Leu Lys Asn Ile Pro Arg Tyr 1025 1030 1035 1040 Leu Ile Pro Cys Tyr Phe Asp Ala Ile Val Ser Gly Val Tyr Asn Val                1045 1050 1055 Leu Ile Asn Gln Val Asn Glu Leu Met Pro Asp Phe Ile Lys Asn Gly            1060 1065 1070 His Ser Phe Pro Gln Ser Leu Ala Leu Ser Thr Leu Gln Phe Leu Ser        1075 1080 1085 Val Cys Lys Ser Ala Asn Leu Pro Gly Phe Ser Pro Ala Leu Ser Pro    1090 1095 1100 Pro Lys Pro Pro Lys Gln Cys Val Thr Leu Ser Ala Gly Leu Pro His 1105 1110 1115 1120 Phe Ser Thr Gly Tyr Met Arg Cys Trp Gly Arg Asp Thr Phe Ile Ala                1125 1130 1135 Leu Arg Gly Ser Met Phe Leu Thr Gly Arg Tyr Asn Glu Ala Arg Phe            1140 1145 1150 Ile Ile Ile Gly Phe Gly Ile Ile Pro Asn        1155 1160 1165 Leu Leu Asp Ser Gly Ser Lys Pro Arg Phe Asn Cys Arg Asp Ala Ile    1170 1175 1180 Trp Trp Trp Met Tyr Cys Ile Lys Gln Tyr Val Glu Asp Ala Pro Lys 1185 1190 1195 1200 Gly Ala Glu Ile Leu Lys Asp Lys Val Ser Arg Ile Phe Pro Tyr Asp                1205 1210 1215 Asp Ala Asp Ala His Ala Pro Gly Ala Phe Asp Gln Leu Leu Phe Asp            1220 1225 1230 Val Met Gln Glu Ala Leu Gln Val His Phe Gln Gly Leu Gln Tyr Arg        1235 1240 1245 Glu Arg Asn Ala Gly Tyr Glu Ile Asp Ala His Met Val Asp Gln Gly    1250 1255 1260 Phe Asn Asn Gln Ile Gly Ile His Pro Glu Thr Gly Phe Val Phe Gly 1265 1270 1275 1280 Gly Asn Asn Phe Asn Cys Gly Thr Trp Met Asp Lys Met Gly Ser Ser                1285 1290 1295 Gln Lys Ala Gly Asn Lys Gly Arg Pro Ser Thr Pro Arg Asp Gly Ser            1300 1305 1310 Ala Val Glu Leu Val Gly Leu Gln Tyr Ala Val Leu Arg Phe Met Gln        1315 1320 1325 Ser Leu Ala Glu Lys Glu Val Ile Pro Tyr Thr Gly Val Glu Arg Lys    1330 1335 1340 Gly Pro Ser Gly Glu Val Thr Lys Trp Ser Tyr Lys Glu Trp Ala Asp 1345 1350 1355 1360 Arg Ile Lys Asn Asn Phe Asp Lys Tyr Phe Phe Val Ser Glu Ser Glu                1365 1370 1375 Thr Cys Ser Val Ala Asn Lys Lys Leu Ile Tyr Lys Asp Ser Tyr Gly            1380 1385 1390 Ala Thr Gln Ser Trp Thr Asp Tyr Gln Leu Arg Cys Asn Phe Pro Ile        1395 1400 1405 Thr Leu Thr Val Ala Pro Asp Leu Cys Asn Pro Gln Asn Ala Trp Arg    1410 1415 1420 Ala Leu Glu Arg Ala Lys Lys Tyr Leu Leu Gly Pro Leu Gly Met Lys 1425 1430 1435 1440 Thr Met Asp Pro Glu Asp Trp Asn Tyr Arg Ala Asn Tyr Asp Asn Ser                1445 1450 1455 Asn Asp Ser Thr Asp Cys Thr Val Ala His Gly Ala Asn Tyr His Gln            1460 1465 1470 Gly Pro Glu Trp Val Trp Pro Ile Gly Phe Tyr Leu Arg Ala Arg Leu        1475 1480 1485 Ile Phe Ala Lys Lys Cys Gly His Leu Asp Glu Thr Ile Ala Glu Thr    1490 1495 1500 Trp Ala Ile Leu Arg Ala His Leu Arg Glu Leu Gln Thr Ser His Trp 1505 1510 1515 1520 Arg Gly Leu Pro Glu Leu Thr Asn Asp Asn Gly Ser Tyr Cys Gly Asp                1525 1530 1535 Ser Cys Arg Thr Gln Ala Trp Ser Val Ala Ile Leu Glu Val Leu            1540 1545 1550 Tyr Asp Leu His Ser Leu Gly Ala Asp Val Ala        1555 1560 <210> 11 <211> 1542 <212> PRT <213> Drosophila sp. <400> 11 Met Ser Thr Met Gly Lys Glu Thr Glu Ser His Ser Ile Pro Ile Ser   1 5 10 15 Glu Gly Gln Asp Ala Glu His Ile Leu Tyr Arg Leu Lys Arg Gly Ser              20 25 30 Lys Leu Ser Val His Pro Asp Ala Ser Leu Leu Gly Arg Lys Ile Val          35 40 45 Leu Tyr Thr Asn Tyr Pro Ala Glu Gly Gln Lys Phe Val Arg Thr Glu      50 55 60 Tyr Arg Val Leu Gly Trp Gln Leu Ser Asn Gly Lys Gln Ile Thr Ser  65 70 75 80 Val Met His Pro Glu Ala His Val Val Asp Thr Asp Ile Arg Ser Gln                  85 90 95 Val Glu Leu Asn Met Ser Gly Thr Tyr His Phe Tyr Phe Arg Tyr Leu             100 105 110 Glu Arg Pro Asp Thr Gly Cys Ser Gly Ala Asp Gly Ala Leu Tyr Val         115 120 125 Gln Val Glu Pro Thr Leu His Val Gly Pro Pro Gly Ala Gln Lys Thr     130 135 140 Ile Pro Leu Asp Ser Val Arg Cys Gln Thr Val Leu Ala Lys Leu Leu 145 150 155 160 Gly Pro Leu Asp Thr Trp Glu Pro Lys Leu Arg Val Ala Lys Glu Ala                 165 170 175 Gly Tyr Asn Val Ile His Phe Thr Pro Ile Gln Glu Leu Gly Gly Ser             180 185 190 Arg Ser Cys Tyr Ser Leu Arg Asp Gln Leu Lys Val Asn Ser His Phe         195 200 205 Ala Pro Gln Lys Gly Gly Lys Ile Ser Phe Glu Asp Val Glu Lys Val     210 215 220 Ile Lys Lys Cys Arg Gln Glu Trp Gly Val Ala Ser Ile Cys Asp Ile 225 230 235 240 Val Leu Asn His Thr Ala Asn Glu Ser Asp Trp Leu Leu Gln His Pro                 245 250 255 Asp Ala Thr Tyr Ser Cys Ala Thr Cys Pro Tyr Leu Arg Pro Ala Phe             260 265 270 Leu Leu Asp Ala Thr Phe Ala Gln Cys Gly Ala Asp Ile Ala Glu Gly         275 280 285 Ser Leu Glu His Val Gly Val Pro Ala Val Ile Glu Gln Glu Cys His     290 295 300 Leu Glu Ala Leu Lys Tyr Gln Leu His Thr Ser Tyr Met Ser Lys Val 305 310 315 320 Asn Ile His Glu Leu Tyr Gln Cys Asp Val Met Lys Tyr Val Asn Glu                 325 330 335 Phe Met Ser Gln Val Arg Thr Arg Glu Pro Pro Lys Asn Val Ala Asn             340 345 350 Glu Cys Arg Phe Gln Glu Ile Gln Leu Ile Gln Asp Pro Gln Tyr Arg         355 360 365 Arg Leu Ala Ser Thr Ile Asn Phe Glu Leu Ala Leu Glu Ile Phe Asn     370 375 380 Ala Phe His Gly Asp Cys Phe Asp Glu Glu Ser Arg Phe Arg Lys Cys 385 390 395 400 Ala Glu Thr Leu Arg Arg His Leu Asp Ala Leu Asn Asp Arg Val Arg                 405 410 415 Cys Glu Val Gln Gly Tyr Ile Asn Tyr Ala Ile Asp Asn Val Leu Ala             420 425 430 Gly Val Arg Tyr Glu Arg Val Gln Gly Asp Gly Pro Arg Val Lys Glu         435 440 445 Ile Ser Glu Lys His Ser Val Phe Met Val Tyr Phe Thr His Thr Gly     450 455 460 Thr Gln Gly Lys Ser Leu Thr Glu Ile Glu Ala Asp Met Tyr Thr Lys 465 470 475 480 Ala Gly Glu Phe Phe Met Ala His His Gly Trp Val Met Gly Tyr Ser                 485 490 495 Asp Pro Leu Arg Asp Phe Ala Glu Glu Gln Pro Gly Arg Ala Asn Val             500 505 510 Tyr Leu Lys Arg Glu Leu Ile Ser Trp Gly Asp Ser Val Lys Leu Arg         515 520 525 Phe Gly Arg Arg Pro Glu Asp Ser Pro Tyr Leu Trp Gln His Met Thr     530 535 540 Glu Tyr Val Gln Thr Thr Ala Arg Ile Phe Asp Gly Val Arg Leu Asp 545 550 555 560 Asn Cys His Ser Thr Pro Leu His Val Ala Glu Tyr Leu Leu Asp Ala                 565 570 575 Ala Arg Lys Ile Asn Pro Glu Leu Tyr Val Val Ala Glu Leu Phe Thr             580 585 590 Asn Ser Asp Tyr Thr Asp Asn Val Phe Val Asn Arg Leu Gly Ile Thr         595 600 605 Ser Leu Ile Arg Glu Ala Leu Ser Ala Trp Asp Ser His Glu Gln Gly     610 615 620 Arg Leu Val Tyr Arg Tyr Gly Gly Val Val Gly Gly Phe Gln Ala 625 630 635 640 Asn Ser Ser Arg His Glu Ala Thr Ser Val Ala His Ala Leu Phe Leu                 645 650 655 Asp Leu Thr His Asp Asn Pro Ser Pro Val Glu Lys Arg Ser Val Tyr             660 665 670 Asp Leu Leu Pro Ser Ala Leu Val Ser Ala Cys Cys Ala Thr         675 680 685 Gly Ser Asn Arg Gly Tyr Asp Glu Leu Val Pro His His Ile His Val     690 695 700 Val Asp Glu Glu Arg Thr Tyr Gln Glu Trp Gly Lys Gly Val Asp Ser 705 710 715 720 Lys Ser Gly Ile Met Gly Ala Lys Arg Ala Leu Asn Leu Leu His Gly                 725 730 735 Gln Leu Ala Glu Glu Gly Phe Ser Gln Val Tyr Val Asp Gln Met Asp             740 745 750 Pro Asn Val Ala Val Thr Arg His Ser Pro Ile Thr His Gln Ser         755 760 765 Val Ile Leu Val Ala His Thr Ala Phe Gly Tyr Pro Ser Pro Asn Ala     770 775 780 Gly Pro Thr Gly Ile Arg Pro Leu Arg Phe Glu Gly Val Leu Asp Glu 785 790 795 800 Ile Ile Leu Glu Ala Ser Leu Thr Met Gln Ser Asp Lys Pro Phe Asp                 805 810 815 Arg Pro Ala Pro Phe Lys Lys Asp Pro Asn Val Ile Asn Gly Phe Thr             820 825 830 Gln Phe Gln Leu Asn Leu Gln Glu His Ile Pro Leu Ala Lys Ser Thr         835 840 845 Val Phe Gln Thr Gln Ala Tyr Ser Asp Gly Asn Asn Thr Glu Leu Asn     850 855 860 Phe Ala Asn Leu Arg Pro Gly Thr Val Val Ala Ile Arg Val Ser Met 865 870 875 880 His Pro Gly Pro Arg Thr Ser Phe Asp Lys Leu Gln Lys Ile Ser Ala                 885 890 895 Ala Leu Arg Ile Gly Ser Gly Glu Glu Tyr Ser Gln Leu Gln Ala Ile             900 905 910 Val Ser Lys Leu Asp Leu Val Ala Leu Ser Gly Ala Leu Phe Ser Cys         915 920 925 Asp Asp Glu Glu Arg Asp Leu Gly Lys Gly Gly Thr Ala Tyr Asp Ile     930 935 940 Pro Asn Phe Gly Lys Ile Val Tyr Cys Gly Leu Gln Gly Phe Ile Ser 945 950 955 960 Leu Leu Thr Glu Ile Ser Pro Lys Asn Asp Leu Gly His Pro Leu Cys                 965 970 975 Asn Asn Leu Arg Asp Gly Asn Trp Met Met Asp Tyr Ile Ser Asp Arg             980 985 990 Leu Thr Ser Tyr Glu Asp Leu Lys Pro Leu Ser Ala Trp Phe Lys Ala         995 1000 1005 Thr Phe Glu Pro Leu Lys Asn Ile Pro Arg Tyr Leu Ile Pro Cys Tyr    1010 1015 1020 Phe Asp Ala Ile Val Ser Gly Val Tyr Asn Val Leu Ile Asn Gln Val 1025 1030 1035 1040 Asn Glu Leu Met Pro Asp Phe Ile Lys Asn Gly His Ser Phe Pro Gln                1045 1050 1055 Ser Leu Ala Leu Ser Thr Leu Gln Phe Leu Ser Val Cys Lys Ser Ala            1060 1065 1070 Asn Leu Pro Gly Phe Ser Pro Ala Leu Ser Pro Pro Lys Pro Pro Lys        1075 1080 1085 Gln Cys Val Thr Leu Ser Ala Gly Leu Pro His Phe Ser Thr Gly Tyr    1090 1095 1100 Met Arg Cys Trp Gly Arg Asp Thr Phe Ile Ala Leu Arg Gly Ser Met 1105 1110 1115 1120 Phe Leu Thr Gly Arg Tyr Asn Gly Ala Arg Phe Ile Ile Ile Gly Phe                1125 1130 1135 Gly Gln Thr Leu Arg His Gly Leu Ile Pro Asn Leu Leu Asp Ser Gly            1140 1145 1150 Ser Lys Pro Arg Phe Asn Cys Arg Asp Ala Ile Trp Trp Trp Met Tyr        1155 1160 1165 Cys Ile Lys Gln Tyr Val Glu Asp Ala Pro Lys Gly Ala Glu Ile Leu    1170 1175 1180 Lys Asp Lys Val Ser Arg Ile Phe Pro Tyr Asp Asp Ala Asp Ala His 1185 1190 1195 1200 Ala Pro Gly Ala Phe Asp Gln Leu Leu Phe Asp Val Met Gln Glu Ala                1205 1210 1215 Leu Gln Val His Phe Gln Gly Leu Gln Tyr Arg Glu Arg Asn Ala Gly            1220 1225 1230 Tyr Glu Ile Asp Ala His Met Val Asp Gln Gly Phe Asn Asn Gln Ile        1235 1240 1245 Gly Ile His Pro Glu Thr Gly Phe Val Phe Gly Gly Asn Asn Phe Asn    1250 1255 1260 Cys Gly Thr Trp Met Asp Lys Met Gly Ser Ser Gln Lys Ala Gly Asn 1265 1270 1275 1280 Lys Gly Arg Pro Ser Thr Pro Arg Asp Gly Ser Ala Val Glu Leu Val                1285 1290 1295 Gly Leu Gln Tyr Ala Val Leu Arg Phe Met Gln Ser Leu Ala Glu Lys            1300 1305 1310 Glu Val Ile Pro Tyr Thr Gly Val Glu Arg Lys Gly Pro Ser Gly Glu        1315 1320 1325 Val Thr Lys Trp Ser Tyr Lys Glu Trp Ala Asp Arg Ile Lys Asn Asn    1330 1335 1340 Phe Asp Lys Tyr Phe Phe Val Ser Glu Ser Glu Thr Cys Ser Val Ala 1345 1350 1355 1360 Asn Lys Lys Leu Ile Tyr Lys Asp Ser Tyr Gly Ala Thr Gln Ser Trp                1365 1370 1375 Thr Asp Tyr Gln Leu Arg Cys Asn Phe Pro Ile Thr Leu Thr Val Ala            1380 1385 1390 Pro Asp Leu Cys Asn Pro Gln Asn Ala Trp Arg Ala Leu Glu Arg Ala        1395 1400 1405 Lys Lys Tyr Leu Leu Gly Pro Leu Gly Met Lys Thr Met Asp Pro Glu    1410 1415 1420 Asp Trp Asn Tyr Arg Ala Asn Tyr Asp Asn Ser Asn Asp Ser Thr Asp 1425 1430 1435 1440 Cys Thr Val Ala His Gly Ala Asn Tyr His Gln Gly Pro Glu Trp Val                1445 1450 1455 Trp Pro Ile Gly Phe Tyr Leu Arg Ala Arg Leu Ile Phe Ala Lys Lys            1460 1465 1470 Cys Gly His Leu Asp Glu Thr Ile Ala Glu Thr Trp Ala Ile Leu Arg        1475 1480 1485 Ala His Leu Arg Glu Leu Gln Thr Ser His Trp Arg Gly Leu Pro Glu    1490 1495 1500 Leu Thr Asn Asp Asn Gly Ser Tyr Cys Gly Asp Ser Cys Arg Thr Gln 1505 1510 1515 1520 Ala Trp Ser Val Ala Ile Leu Glu Val Leu Tyr Asp Leu His Ser                1525 1530 1535 Leu Gly Ala Asp Val Ala            1540 <210> 12 <211> 1542 <212> PRT <213> Drosophila sp. <400> 12 Met Ser Thr Met Gly Lys Glu Thr Glu Ser His Ser Ile Pro Ile Ser   1 5 10 15 Glu Gly Gln Asp Ala Glu His Ile Leu Tyr Arg Leu Lys Arg Gly Ser              20 25 30 Lys Leu Ser Val His Pro Asp Ala Ser Leu Leu Gly Arg Lys Ile Val          35 40 45 Leu Tyr Thr Asn Tyr Pro Ala Glu Gly Gln Lys Phe Val Arg Thr Glu      50 55 60 Tyr Arg Val Leu Gly Trp Gln Leu Ser Asn Gly Lys Gln Ile Thr Ser  65 70 75 80 Val Met His Pro Glu Ala His Val Val Asp Thr Asp Ile Arg Ser Gln                  85 90 95 Val Glu Leu Asn Met Ser Gly Thr Tyr His Phe Tyr Phe Arg Tyr Leu             100 105 110 Glu Arg Pro Asp Thr Gly Cys Ser Gly Ala Asp Gly Ala Leu Tyr Val         115 120 125 Gln Val Glu Pro Thr Leu His Val Gly Pro Pro Gly Ala Gln Lys Thr     130 135 140 Ile Pro Leu Asp Ser Val Arg Cys Gln Thr Val Leu Ala Lys Leu Leu 145 150 155 160 Gly Pro Leu Asp Thr Trp Glu Pro Lys Leu Arg Val Ala Lys Glu Ala                 165 170 175 Gly Tyr Asn Val Ile His Phe Thr Pro Ile Gln Glu Leu Gly Gly Ser             180 185 190 Arg Ser Cys Tyr Ser Leu Arg Asp Gln Leu Lys Val Asn Ser His Phe         195 200 205 Ala Pro Gln Lys Gly Gly Lys Ile Ser Phe Glu Asp Val Glu Lys Val     210 215 220 Ile Lys Lys Cys Arg Gln Glu Trp Gly Val Ala Ser Ile Cys Asp Ile 225 230 235 240 Val Leu Asn His Thr Ala Asn Glu Ser Asp Trp Leu Leu Gln His Pro                 245 250 255 Asp Ala Thr Tyr Ser Cys Ala Thr Cys Pro Tyr Leu Arg Pro Ala Phe             260 265 270 Leu Leu Asp Ala Thr Phe Ala Gln Cys Gly Ala Asp Ile Ala Glu Gly         275 280 285 Ser Leu Glu His Val Gly Val Pro Ala Val Ile Glu Gln Glu Cys His     290 295 300 Leu Glu Ala Leu Lys Tyr Gln Leu His Thr Ser Tyr Met Ser Lys Val 305 310 315 320 Asn Ile His Glu Leu Tyr Gln Cys Asp Val Met Lys Tyr Val Asn Glu                 325 330 335 Phe Met Ser Gln Val Arg Thr Arg Glu Pro Pro Lys Asn Val Ala Asn             340 345 350 Glu Cys Arg Phe Gln Glu Ile Gln Leu Ile Gln Asp Pro Gln Tyr Arg         355 360 365 Arg Leu Ala Ser Thr Ile Asn Phe Glu Leu Ala Leu Glu Ile Phe Asn     370 375 380 Ala Phe His Gly Asp Cys Phe Asp Glu Glu Ser Arg Phe Arg Lys Cys 385 390 395 400 Ala Glu Thr Leu Arg Arg His Leu Asp Ala Leu Asn Asp Arg Val Arg                 405 410 415 Cys Glu Val Gln Gly Tyr Ile Asn Tyr Ala Ile Asp Asn Val Leu Ala             420 425 430 Gly Val Arg Tyr Glu Arg Val Gln Gly Asp Gly Pro Arg Val Lys Glu         435 440 445 Ile Ser Glu Lys His Ser Val Phe Met Val Tyr Phe Thr His Thr Gly     450 455 460 Thr Gln Gly Lys Ser Leu Thr Glu Ile Glu Ala Asp Met Tyr Thr Lys 465 470 475 480 Ala Gly Glu Phe Phe Met Ala His His Gly Trp Val Met Gly Tyr Ser                 485 490 495 Asp Pro Leu Arg Asp Phe Ala Glu Glu Gln Pro Gly Arg Ala Asn Val             500 505 510 Tyr Leu Lys Arg Glu Leu Ile Ser Trp Gly Asp Ser Val Lys Leu Arg         515 520 525 Phe Gly Arg Arg Pro Glu Asp Ser Pro Tyr Leu Trp Gln His Met Thr     530 535 540 Glu Tyr Val Gln Thr Thr Ala Arg Ile Phe Asp Gly Val Arg Leu Asp 545 550 555 560 Asn Cys His Ser Thr Pro Leu His Val Ala Glu Tyr Leu Leu Asp Ala                 565 570 575 Ala Arg Lys Ile Asn Pro Glu Leu Tyr Val Val Ala Glu Leu Phe Thr             580 585 590 Asn Ser Asp Tyr Thr Asp Asn Val Phe Val Asn Arg Leu Gly Ile Thr         595 600 605 Ser Leu Ile Arg Glu Ala Leu Ser Ala Trp Asp Ser His Glu Gln Gly     610 615 620 Arg Leu Val Tyr Arg Tyr Gly Gly Val Val Gly Gly Phe Gln Ala 625 630 635 640 Asn Ser Ser Arg His Glu Ala Thr Ser Val Ala His Ala Leu Phe Leu                 645 650 655 Asp Leu Thr His Asp Asn Pro Ser Pro Val Glu Lys Arg Ser Val Tyr             660 665 670 Asp Leu Leu Pro Ser Ala Leu Val Ser Ala Cys Cys Ala Thr         675 680 685 Gly Ser Asn Arg Gly Tyr Asp Glu Leu Val Pro His His Ile His Val     690 695 700 Val Asp Glu Glu Arg Thr Tyr Gln Glu Trp Gly Lys Gly Val Asp Ser 705 710 715 720 Lys Ser Gly Ile Met Gly Ala Lys Arg Ala Leu Asn Leu Leu His Gly                 725 730 735 Gln Leu Ala Glu Glu Gly Phe Ser Gln Val Tyr Val Asp Gln Met Asp             740 745 750 Pro Asn Val Ala Val Thr Arg His Ser Pro Ile Thr His Gln Ser         755 760 765 Val Ile Leu Val Ala His Thr Ala Phe Gly Tyr Pro Ser Pro Asn Ala     770 775 780 Gly Pro Thr Gly Ile Arg Pro Leu Arg Phe Glu Gly Val Leu Asp Glu 785 790 795 800 Ile Ile Leu Glu Ala Ser Leu Thr Met Gln Ser Asp Lys Pro Phe Asp                 805 810 815 Arg Pro Ala Pro Phe Lys Lys Asp Pro Asn Val Ile Asn Gly Phe Thr             820 825 830 Gln Phe Gln Leu Asn Leu Gln Glu His Ile Pro Leu Ala Lys Ser Thr         835 840 845 Val Phe Gln Thr Gln Ala Tyr Ser Asp Gly Asn Asn Thr Glu Leu Asn     850 855 860 Phe Ala Asn Leu Arg Pro Gly Thr Val Val Ala Ile Arg Val Ser Met 865 870 875 880 His Pro Gly Pro Arg Thr Ser Phe Asp Lys Leu Gln Lys Ile Ser Ala                 885 890 895 Ala Leu Arg Ile Gly Ser Gly Glu Glu Tyr Ser Gln Leu Gln Ala Ile             900 905 910 Val Ser Lys Leu Asp Leu Val Ala Leu Ser Gly Ala Leu Phe Ser Cys         915 920 925 Asp Asp Glu Glu Arg Asp Leu Gly Lys Gly Gly Thr Ala Tyr Asp Ile     930 935 940 Pro Asn Phe Gly Lys Ile Val Tyr Cys Gly Leu Gln Gly Phe Ile Ser 945 950 955 960 Leu Leu Thr Glu Ile Ser Pro Lys Asn Asp Leu Gly His Pro Leu Cys                 965 970 975 Asn Asn Leu Arg Asp Gly Asn Trp Met Met Asp Tyr Ile Ser Asp Arg             980 985 990 Leu Thr Ser Tyr Glu Asp Leu Lys Pro Leu Ser Ala Trp Phe Lys Ala         995 1000 1005 Thr Phe Glu Pro Leu Lys Asn Ile Pro Arg Tyr Leu Ile Pro Cys Tyr    1010 1015 1020 Phe Asp Ala Ile Val Ser Gly Val Tyr Asn Val Leu Ile Asn Gln Val 1025 1030 1035 1040 Asn Glu Leu Met Pro Asp Phe Ile Lys Asn Gly His Ser Phe Pro Gln                1045 1050 1055 Ser Leu Ala Leu Ser Thr Leu Gln Phe Leu Ser Val Cys Lys Ser Ala            1060 1065 1070 Asn Leu Pro Gly Phe Ser Pro Ala Leu Ser Pro Pro Lys Pro Pro Lys        1075 1080 1085 Gln Cys Val Thr Leu Ser Ala Gly Leu Pro His Phe Ser Thr Gly Tyr    1090 1095 1100 Met Arg Cys Trp Gly Arg Asp Thr Phe Ile Ala Leu Arg Gly Ser Met 1105 1110 1115 1120 Phe Leu Thr Gly Arg Tyr Asn Gly Ala Arg Phe Ile Ile Ile Gly Phe                1125 1130 1135 Gly Gln Thr Leu Arg His Gly Leu Ile Pro Asn Leu Leu Asp Ser Gly            1140 1145 1150 Ser Lys Pro Arg Phe Asn Cys Arg Asp Ala Ile Trp Trp Trp Met Tyr        1155 1160 1165 Cys Ile Lys Gln Tyr Val Glu Asp Ala Pro Lys Gly Ala Glu Ile Leu    1170 1175 1180 Lys Asp Lys Val Ser Arg Ile Phe Pro Tyr Asp Asp Ala Asp Ala His 1185 1190 1195 1200 Ala Pro Gly Ala Phe Asp Gln Leu Leu Phe Asp Val Met Gln Glu Ala                1205 1210 1215 Leu Gln Val His Phe Gln Gly Leu Gln Tyr Arg Glu Arg Asn Ala Gly            1220 1225 1230 Tyr Glu Ile Asp Ala His Met Val Asp Gln Gly Phe Asn Asn Gln Ile        1235 1240 1245 Gly Ile His Pro Glu Thr Gly Phe Val Phe Gly Gly Asn Asn Phe Asn    1250 1255 1260 Cys Gly Thr Trp Met Asp Lys Met Gly Ser Ser Gln Lys Ala Gly Asn 1265 1270 1275 1280 Lys Gly Arg Pro Ser Thr Pro Arg Asp Gly Ser Ala Val Glu Leu Val                1285 1290 1295 Gly Leu Gln Tyr Ala Val Leu Arg Phe Met Gln Ser Leu Ala Glu Lys            1300 1305 1310 Glu Val Ile Pro Tyr Thr Gly Val Glu Arg Lys Gly Pro Ser Gly Glu        1315 1320 1325 Val Thr Lys Trp Ser Tyr Lys Glu Trp Ala Asp Arg Ile Lys Asn Asn    1330 1335 1340 Phe Asp Lys Tyr Phe Phe Val Ser Glu Ser Glu Thr Cys Ser Val Ala 1345 1350 1355 1360 Asn Lys Lys Leu Ile Tyr Lys Asp Ser Tyr Gly Ala Thr Gln Ser Trp                1365 1370 1375 Thr Asp Tyr Gln Leu Arg Cys Asn Phe Pro Ile Thr Leu Thr Val Ala            1380 1385 1390 Pro Asp Leu Cys Asn Pro Gln Asn Ala Trp Arg Ala Leu Glu Arg Ala        1395 1400 1405 Lys Lys Tyr Leu Leu Gly Pro Leu Gly Met Lys Thr Met Asp Pro Glu    1410 1415 1420 Asp Trp Asn Tyr Arg Ala Asn Tyr Asp Asn Ser Asn Asp Ser Thr Asp 1425 1430 1435 1440 Cys Thr Val Ala His Gly Ala Asn Tyr His Gln Gly Pro Glu Trp Val                1445 1450 1455 Trp Pro Ile Gly Phe Tyr Leu Arg Ala Arg Leu Ile Phe Ala Lys Lys            1460 1465 1470 Cys Gly His Leu Asp Glu Thr Ile Ala Glu Thr Trp Ala Ile Leu Arg        1475 1480 1485 Ala His Leu Arg Glu Leu Gln Thr Ser His Trp Arg Gly Leu Pro Glu    1490 1495 1500 Leu Thr Asn Asp Asn Gly Ser Tyr Cys Gly Asp Ser Cys Arg Thr Gln 1505 1510 1515 1520 Ala Trp Ser Val Ala Ile Leu Glu Val Leu Tyr Asp Leu His Ser                1525 1530 1535 Leu Gly Ala Asp Val Ala            1540

Claims (17)

A nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, a complementary base sequence thereof, Wherein the nucleotide sequence is at least one nucleotide sequence selected from the group consisting of SEQ ID NOs. The method according to claim 1,
Wherein the amount of the biomarker expressed is reduced as the progress of aging of the diagnostic subject is promoted. delete delete delete delete A biomarker composition according to claim 1; And a hybridization solution. 8. The method of claim 7,
The biomarker may be present in a dispersed form in solution. Wherein the agar plate is present in the form of a microarray immobilized on a substrate. delete delete delete delete A nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, a complementary base sequence thereof, A biomarker composition comprising any one of the base sequences; And a hybridization solution; and a diagnostic kit for simultaneous detection of aging progression discrimination, obesity discrimination and cancer diagnosis I) isolating and extracting RNA from isolated cells or tissues of the diagnostic individual;
II) contacting the separated RNA or a cDNA synthesized therefrom with the kit according to claim 7 to hybridize the RNA or cDNA with the biomarker; And
III) detecting the degree of hybridization between the biomarker and the RNA or cDNA, and providing information necessary for the determination of aging progress. delete delete I) isolating and extracting RNA from isolated cells or tissues of the diagnostic individual;
II) contacting the isolated RNA or a cDNA synthesized therefrom with the kit according to claim 13 to hybridize the RNA or cDNA with the biomarker; And
III) detecting the degree of hybridization between the biomarker and the RNA or cDNA, and simultaneously providing information necessary for the determination of aging progress, discrimination of increase in obesity, and cancer diagnosis.

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