JPH0870875A - Recombined alkali phosphatase-fused protein - Google Patents

Abstract

PURPOSE: To obtain the recombined alkali phosphatase-fused antibody high in activity, excellent in uniformity, and suitable as a target antibody used for an immunochemical measurement requiring high sensitivity and high accuracy. CONSTITUTION: This recombined alkali phosphatase-fused antibody is obtained by culturing a host cell transformed with a single expression vector and/or a set of plural expression vectors which can independently express three kinds of genes consisting of the first gene: a gene coding the H chain V and CH1 regions of an antibody, or the amino acid sequence of its derivative, the second gene: a gene coding the L chain of the antibody or the amino acid sequence of its derivative, the third gene: a gene coding alkali phosphatase or the amino acid sequence of its derivative, and subsequently separating the expression product of the above-mentioned gene from the culture product. The antibody is preferably used for immunochemical measurements.

Description

【発明の詳細な説明】Detailed Description of the Invention

【０００１】[0001]

【産業上の利用分野】本発明は、組換えアルカリフォス
ファタ−ゼ融合タンパク質に関するものである。TECHNICAL FIELD The present invention relates to a recombinant alkaline phosphatase fusion protein.

【０００２】[0002]

【従来の技術】アルカリフォスファタ−ゼ（以下、「Ａ
Ｐ」）は、最適ｐＨをアルカリ性に持ち、リン酸モノエ
ステル結合を加水分解する酵素で、免疫化学的測定法の
標識酵素等として頻繁に利用されている。肝骨腎由来、
胎盤由来、腸管由来等の多くのアイソタイプが知られて
いるが、免疫化学的測定等の目的では、入手が容易な牛
小腸由来のものが用いられている。2. Description of the Related Art Alkaline phosphatase (hereinafter referred to as "A
P ") is an enzyme that has an optimum pH alkaline and hydrolyzes a phosphate monoester bond, and is frequently used as a labeling enzyme for immunochemical assay. Derived from hepato-osseous kidney,
Many isotypes such as those derived from placenta and intestinal tract are known, but those derived from bovine small intestine that are easily available are used for the purpose of immunochemical measurement and the like.

【０００３】免疫化学的測定においては、ＡＰを抗体等
の免疫試薬と結合して使用するのが普通であるが、通
常、結合には化学的な方法が用いられている。化学的な
方法としては、例えば、ＳＡＭＳＡ（Ｓ−アセチルメル
カプトサクシニルアンヒドライド）やＳＰＤＰ（Ｎ−サ
クシイミジル３−（２−ピリジルジチオ）プロピオネ−
ト）によるＮＨ₂ 基へのＳＨ基の導入と２つのＳＨ基の
酸化による方法等が知られている。[0003] In immunochemical measurement, AP is usually used in combination with an immunoreagent such as an antibody, but a chemical method is usually used for binding. Examples of the chemical method include SAMSA (S-acetylmercaptosuccinyl anhydride) and SPDP (N-succinimidyl 3- (2-pyridyldithio) propione-).
The method of introducing an SH group into the NH ₂ group and oxidizing the two SH groups is known.

【０００４】[0004]

【従来技術の課題】以下、抗体とＡＰとの化学的結合を
例に記載するが、免疫化学的測定等において使用される
他の試薬、例えば競合測定において使用されるリガンド
とＡＰとの結合タンパク質等についても状況は同様であ
る。化学的結合では、まず、官能基を特定の場所に導入
することが不可能である。例えば、ＳＡＭＳＡにより抗
体及びＡＰ分子にＳＨ基を導入する際には、タンパク質
のＮ末端のＮＨ₂ 基、リジン残基のＮＨ₂ 基及びアルギ
ニン残基のＮＨ₂ 基の全てが対象となるため、反応の強
度の調節により分子当たりの平均的な導入数は調節し得
ても、各分子への導入場所や導入数のばらつきは調節し
得ない。導入位置によっては機能部位の破壊や立体構造
の歪みが起こり得るため、この様な官能基の導入によ
り、一定の比率で抗体やＡＰの本来の機能が損なわれる
恐れもある。2. Description of the Related Art A chemical bond between an antibody and AP will be described below as an example, but other reagents used in immunochemical assay, for example, a binding protein between AP and a ligand used in competitive assay. The situation is the same for such cases. First, it is impossible to introduce a functional group into a specific place by chemical bonding. For example, when introducing an SH group in the antibodies and AP molecules by SAMSA, since the NH ₂ groups of the N-terminus of the protein, all of NH ₂ groups of NH ₂ groups and arginine residues of lysine residues of interest, Although the average number of introductions per molecule can be adjusted by adjusting the intensity of the reaction, it is not possible to adjust the site of introduction into each molecule and the variation in the number of introductions. Since the functional site may be destroyed or the three-dimensional structure may be distorted depending on the introduction position, introduction of such a functional group may impair the original function of the antibody or AP at a constant ratio.

【０００５】次に、官能基を導入した抗体とＡＰを結合
させる場合にも、目的とする抗体とＡＰとの結合タンパ
ク質だけを作製することは不可能である。例えば、ＳＨ
基を導入したＡＰと同じくＳＨ基を導入した抗体を混合
して結合反応を行わせると、目的とするＡＰ結合抗体だ
けでなく、ＡＰ同志の結合物、抗体同志の結合物等も生
じてしまう。また、反応の強度の調節により平均的な結
合数は調節し得ても、結合数を均一化することは不可能
である。さらに融合の際に使われた官能基の位置によっ
ては、機能部位の破壊や立体構造の歪みが起こり、結合
の結果、一定の比率で機能し得ないものが生じることを
防ぎ得ない。[0005] Next, even in the case of binding AP with a functional group-introduced antibody, it is impossible to produce only a binding protein of the target antibody and AP. For example, SH
When a group-introduced AP and an SH-group-introduced antibody are mixed and the binding reaction is performed, not only the target AP-bound antibody but also the AP-bound product, antibody-bound product, etc. are produced. . Further, even if the average number of bonds can be adjusted by adjusting the intensity of the reaction, it is impossible to make the number of bonds uniform. Further, depending on the position of the functional group used in the fusion, destruction of the functional site or distortion of the three-dimensional structure may occur, and as a result of binding, it may not be possible to prevent the generation of some that cannot function at a certain ratio.

【０００６】この様に、化学的結合法は広く使用されて
いるが、目的の性能を有する均一な結合タンパク質を得
るのは困難である。さらに、目的の性能を有しない融合
物を除くことが考えられるが、例えばＡＰと他のタンパ
ク質が１分子ずつ結合した結合タンパク質を目的とした
場合、それ以外の結合タンパク質や未反応タンパク質を
除いて分離精製する場合は収率の低下を招く。また、分
離した結合タンパク質の中から、性能を保持するものと
保持しないものを分離するのは不可能である。以上に説
明してきた様に、抗体はＡＰと結合して用いられる代表
的なタンパク質である。実際の免疫化学的測定法で用い
られているＡＰ結合抗体（いわゆる標識抗体）は、種々
の形態の結合タンパク質及び未反応物の混合物であるこ
とが多い。As described above, although the chemical conjugation method is widely used, it is difficult to obtain a homogeneous bound protein having the desired performance. Furthermore, it is possible to remove fusions that do not have the desired performance. For example, in the case of aiming at a binding protein in which AP and another protein are bound one molecule at a time, other binding proteins and unreacted proteins are excluded. When separated and purified, the yield is lowered. In addition, it is impossible to separate, from the separated binding proteins, those that retain the performance and those that do not retain the performance. As described above, the antibody is a typical protein used by binding to AP. The AP-binding antibody (so-called labeled antibody) used in the actual immunochemical assay method is often a mixture of various forms of binding protein and unreacted antibody.

【０００７】このため、活性を有しかつ均一なＡＰ結合
抗体を用いた免疫化学的測定法は、化学的結合で作製し
たＡＰ結合抗体を用いた場合と比較して、感度や精度を
向上できる可能性がある。特に、微量にしか存在しない
物質を測定することが求められる診断分野、環境分野等
で使用される免疫化学的測定法では、高感度化及び高精
度化が求められる場合が多い。Therefore, the immunochemical assay method using an active and uniform AP-bound antibody can improve the sensitivity and accuracy as compared with the case of using the AP-bound antibody prepared by chemical binding. there is a possibility. In particular, in immunochemical assay methods used in the fields of diagnosis, environment, etc., in which it is required to measure substances that exist only in trace amounts, high sensitivity and high accuracy are often required.

【０００８】近年の遺伝子工学の進歩により、各種タン
パク質を遺伝子工学的に作製することが可能となった。
ＡＰの遺伝子工学的生産方法としては、大腸菌由来ＡＰ
（Mandeckiら、Protein Engineering, 4, p801, 1991年
参照）、ヒト胎盤ＡＰ（Bergerら、J. Biol. Chem., 26
3, p10016, 1988 年参照) 、ヒト小腸ＡＰ（保川ら、特
願平５−７６８８３号）が報告されている。また、抗体
の遺伝子工学的生産方法に関しても多くの報告例がある
（例えばWinterら、Nature、349 、p293、1991年等参
照）。宿主は大腸菌や動物細胞等多岐に渡り、発現抗体
の形態も天然のＩｇＧ型からＦａｂ、Ｆｖ、一本鎖Ｆｖ
等が報告されている。[0008] Recent advances in genetic engineering have made it possible to produce various proteins by genetic engineering.
As a genetically engineered production method of AP, Escherichia coli-derived AP is used.
(See Mandecki et al., Protein Engineering, 4, p801, 1991), human placental AP (Berger et al., J. Biol. Chem., 26.
3, p10016, 1988), and human small intestine AP (Yasukawa et al., Japanese Patent Application No. 5-76883). In addition, there are many reports on methods for producing antibodies by genetic engineering (see, for example, Winter et al., Nature, 349, p293, 1991). There are various hosts such as Escherichia coli and animal cells, and the form of expressed antibody is Fab, Fv, single chain Fv from natural IgG type.
Etc. have been reported.

【０００９】このような技術により調製される、組換え
ＡＰ融合抗体、即ち、ＡＰのアミノ酸配列をコ−ドする
遺伝子と抗体のアミノ酸配列をコ−ドする遺伝子が連結
した遺伝子を含有する発現ベクタ−で形質転換された宿
主を培養し、培養物から採取されるＡＰ融合抗体は、ア
ミノ酸レベルでＡＰと抗体が結合しており、化学的結合
を必要としないため、上記問題を根本的に解決できる可
能性がある。A recombinant AP fusion antibody prepared by such a technique, that is, an expression vector containing a gene in which a gene encoding the amino acid sequence of AP and a gene encoding the amino acid sequence of the antibody are linked The AP-fused antibody obtained by culturing a host transformed with − and collected from the culture has the AP and antibody bound at the amino acid level and does not require chemical binding, and thus fundamentally solves the above problems. There is a possibility.

【００１０】現に、組換えＡＰ融合タンパク質として、
大腸菌で発現させた大腸菌由来アルカリフォスファタ−
ゼ（ＢＡＰ）融合抗体が報告されている（Ducancelら、
Biotechnology 、11、p601〜、1993年参照）。この例で
は、抗原との結合活性やＡＰ酵素活性が確認されている
が、免疫化学的測定に使用するにはＡＰ活性が不十分で
ある。At present, as a recombinant AP fusion protein,
E. coli-derived alkaline phosphatase expressed in E. coli
ZE (BAP) fusion antibody has been reported (Ducancel et al.,
Biotechnology, 11, p601-, 1993). In this example, the binding activity to the antigen and the AP enzyme activity have been confirmed, but the AP activity is insufficient for use in immunochemical measurements.

【００１１】[0011]

【課題を解決するための手段】免疫化学的測定等に使用
するのに十分な活性と均一な性質を有するＡＰ融合抗体
等のＡＰ融合タンパク質の調製に関し、組換えＡＰ融合
タンパク質を鋭意研究した結果、本発明者らは、上記目
的を達成し得る組換えＡＰ融合タンパク質を作成し、本
発明を完成した。即ち本発明は、少なくとも下記３種類
の遺伝子を独立して発現し得る形態で含有する、組換え
ＡＰ融合抗体製造用の単一発現ベクタ−又は複数の発現
ベクタ−のセットである。[Means for Solving the Problems] As a result of diligent research on recombinant AP fusion proteins for the preparation of AP fusion proteins such as AP fusion antibodies having sufficient activity and uniform properties for use in immunochemical measurements and the like. The present inventors have completed the present invention by producing a recombinant AP fusion protein that can achieve the above object. That is, the present invention is a single expression vector or a set of a plurality of expression vectors for producing a recombinant AP fusion antibody, which contains at least the following three kinds of genes in a form capable of independently expressing.

【００１２】第１の遺伝子；抗体のＨ鎖Ｖ及びＣＨ１領
域、又はその誘導体のアミノ酸配列をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にＡＰ又はその誘導体のアミノ酸配列をコ−
ドする遺伝子を含み、その発現により抗体のＨ鎖Ｖ及び
ＣＨ１領域、又はその誘導体とＡＰ又はその誘導体との
融合タンパク質か、あるいは、抗体のＬ鎖又はその誘導
体とＡＰ又はその誘導体との融合タンパク質を発現し得
るものである）。First gene; gene encoding the amino acid sequence of antibody H chain V and CH1 regions or derivatives thereof Second gene; gene encoding the amino acid sequence of antibody L chain or its derivatives A third gene; a gene encoding the amino acid sequence of AP or its derivative (either the first gene or the second gene is further coded downstream with the amino acid sequence of AP or its derivative).
Fusion protein of the antibody H chain V and CH1 region or its derivative with AP or its derivative, or a fusion protein of the antibody L chain or its derivative with AP or its derivative. Can be expressed).

【００１３】また本発明は、少なくとも下記２種類の遺
伝子を独立して発現し得る形態で含有する、組換えＡＰ
融合タンパク質製造用の単一発現ベクタ−又は複数の発
現ベクタ−のセットである。The present invention also provides a recombinant AP containing at least the following two types of genes in a form capable of being independently expressed.
A single expression vector or a set of plural expression vectors for producing a fusion protein.

【００１４】第１の遺伝子；任意のタンパク質又はその
誘導体のアミノ酸配列をコ−ドする遺伝子とその下流の
ＡＰ又はその誘導体のアミノ酸配列をコ−ドする遺伝子
を含み、その発現により任意のタンパク質又はその誘導
体とＡＰ又はその誘導体との融合タンパク質を発現し得
る遺伝子 第２の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 また本発明は、少なくとも下記３種類の遺伝子を独立し
て発現し得る、単一発現ベクタ−及び／又は複数の発現
ベクタ−のセットで形質転換した宿主細胞を培養し、培
養物から前記遺伝子の発現物を取得することを特徴とす
る組換えＡＰ融合抗体の製造方法である。The first gene includes a gene encoding the amino acid sequence of an arbitrary protein or its derivative and a gene encoding the amino acid sequence of AP or its derivative downstream thereof, and the expression of the arbitrary gene or Gene capable of expressing fusion protein of its derivative and AP or its derivative Second gene; Gene encoding amino acid sequence of AP or its derivative Also, the present invention independently expresses at least the following three types of genes. Of a recombinant AP fusion antibody, which comprises culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors, and obtaining an expression product of the gene from the culture. It is a manufacturing method.

【００１５】第１の遺伝子；抗体のＨ鎖Ｖ及びＣＨ１領
域、又はその誘導体のアミノ酸配列をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にＡＰ又はその誘導体のアミノ酸配列をコ−
ドする遺伝子を含み、その発現により抗体のＨ鎖Ｖ及び
ＣＨ１領域、又はその誘導体とＡＰ又はその誘導体との
融合タンパク質か、あるいは、抗体のＬ鎖又はその誘導
体とＡＰ又はその誘導体との融合タンパク質を発現し得
るものである）。First gene; gene encoding the amino acid sequence of antibody H chain V and CH1 region or its derivative Second gene; gene encoding the amino acid sequence of antibody L chain or its derivative A third gene; a gene encoding the amino acid sequence of AP or its derivative (either the first gene or the second gene is further coded downstream with the amino acid sequence of AP or its derivative).
Fusion protein of the antibody H chain V and CH1 region or its derivative with AP or its derivative, or a fusion protein of the antibody L chain or its derivative with AP or its derivative. Can be expressed).

【００１６】また本発明は、少なくとも下記２種類の遺
伝子を独立して発現し得る、単一発現ベクタ−及び／又
は複数の発現ベクタ−のセットで形質転換した宿主細胞
を培養し、培養物から前記遺伝子の発現物を取得するこ
とを特徴とする組換えＡＰ融合タンパク質の製造方法で
ある。 第１の遺伝子；任意のタンパク質又はその誘導体のアミ
ノ酸配列をコ−ドする遺伝子とその下流のＡＰ又はその
誘導体のアミノ酸配列をコ−ドする遺伝子を含み、その
発現により任意のタンパク質又はその誘導体とＡＰ又は
その誘導体との融合タンパク質を発現し得る遺伝子 第２の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 そして本発明は、少なくとも下記３種類の遺伝子を独立
して発現し得る、単一発現ベクタ−及び／又は複数の発
現ベクタ−のセットで形質転換した宿主細胞を培養して
取得される組換えＡＰ融合抗体を使用する、免疫化学的
測定方法である。 第１の遺伝子；抗体のＨ鎖Ｖ及びＣ
Ｈ１領域、又はその誘導体のアミノ酸配列
をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にＡＰ又はその誘導体のアミノ酸配列をコ−
ドする遺伝子を含み、その発現により抗体のＨ鎖Ｖ及び
ＣＨ１領域、又はその誘導体とＡＰ又はその誘導体との
融合タンパク質か、あるいは、抗体のＬ鎖又はその誘導
体とＡＰ又はその誘導体との融合タンパク質を発現し得
るものである）。The present invention also comprises culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following two genes, A method for producing a recombinant AP fusion protein, which comprises obtaining an expression product of the gene. A first gene; including a gene encoding the amino acid sequence of an arbitrary protein or its derivative and a gene encoding the amino acid sequence of AP or its derivative downstream thereof, and expressing it as an arbitrary protein or its derivative A gene capable of expressing a fusion protein with AP or a derivative thereof; a second gene; a gene encoding the amino acid sequence of AP or a derivative thereof, and the present invention can independently express at least the following three types of genes, An immunochemical assay method using a recombinant AP fusion antibody obtained by culturing a host cell transformed with a single expression vector and / or a set of multiple expression vectors. First gene; antibody H chains V and C
Amino acid sequence of H1 region or its derivative
Gene encoding the amino acid sequence of the antibody L chain or its derivative Third gene; Gene encoding the amino acid sequence of AP or its derivative (First gene Alternatively, either one of the second gene and the amino acid sequence of AP or its derivative is further downstream.
Fusion protein of the antibody H chain V and CH1 region or its derivative with AP or its derivative, or a fusion protein of the antibody L chain or its derivative with AP or its derivative. Can be expressed).

【００１７】そして本発明は、少なくとも下記２種類の
遺伝子を独立して発現し得る、単一発現ベクタ−及び／
又は複数の発現ベクタ−のセットで形質転換した宿主細
胞を培養して取得される組換えＡＰ融合タンパク質を使
用する、免疫化学的測定方法である。The present invention provides a single expression vector capable of independently expressing at least the following two types of genes, and / or
Alternatively, it is an immunochemical assay method using a recombinant AP fusion protein obtained by culturing a host cell transformed with a set of a plurality of expression vectors.

【００１８】第１の遺伝子；任意のタンパク質又はその
誘導体のアミノ酸配列をコ−ドする遺伝子とその下流の
ＡＰ又はその誘導体のアミノ酸配列をコ−ドする遺伝子
を含み、その発現により任意のタンパク質又はその誘導
体とＡＰ又はその誘導体との融合タンパク質を発現し得
る遺伝子 第２の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 そして本発明は、少なくとも下記３種類の遺伝子を独立
して発現し得る、単一発現ベクタ−及び／又は複数の発
現ベクタ−のセットで形質転換した宿主細胞を培養して
取得される組換えＡＰ融合抗体を含む、免疫化学的測定
用キットである。 第１の遺伝子；抗体のＨ鎖Ｖ及びＣ
Ｈ１領域、又はその誘導体のアミノ酸配列
をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にＡＰ又はその誘導体のアミノ酸配列をコ−
ドする遺伝子を含み、その発現により抗体のＨ鎖Ｖ及び
ＣＨ１領域、又はその誘導体とＡＰ又はその誘導体との
融合タンパク質か、あるいは、抗体のＬ鎖又はその誘導
体とＡＰ又はその誘導体との融合タンパク質を発現し得
るものである）。The first gene includes a gene encoding the amino acid sequence of an arbitrary protein or its derivative and a gene encoding the amino acid sequence of AP or its derivative downstream thereof, and the expression of the arbitrary gene or Gene capable of expressing fusion protein of its derivative and AP or its derivative Second gene; Gene encoding amino acid sequence of AP or its derivative And the present invention independently expresses at least the following three kinds of genes A kit for immunochemical assay, which comprises a recombinant AP fusion antibody obtained by culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors that can be used. First gene; antibody H chains V and C
Amino acid sequence of H1 region or its derivative
Gene encoding the amino acid sequence of the antibody L chain or its derivative Third gene; Gene encoding the amino acid sequence of AP or its derivative (First gene Alternatively, either one of the second gene and the amino acid sequence of AP or its derivative is further downstream.
Fusion protein of the antibody H chain V and CH1 region or its derivative with AP or its derivative, or a fusion protein of the antibody L chain or its derivative with AP or its derivative. Can be expressed).

【００１９】更に本発明は、少なくとも下記２種類の遺
伝子を独立して発現し得る、単一発現ベクタ−及び／又
は複数の発現ベクタ−のセットで形質転換した宿主細胞
を培養して取得される組換えＡＰ融合タンパク質を含
む、免疫化学的測定用キットである。 第１の遺伝子；任意のタンパク質又はその誘導体のアミ
ノ酸配列をコ−ドする遺伝子とその下流のＡＰ又はその
誘導体のアミノ酸配列をコ−ドする遺伝子を含み、その
発現により任意のタンパク質又はその誘導体とＡＰ又は
その誘導体との融合タンパク質を発現し得る遺伝子 第２の遺伝子；ＡＰ又はその誘導体のアミノ酸配列をコ
−ドする遺伝子 本発明で使用するＡＰのアミノ酸配列をコ−ドする遺伝
子は、それが発現した場合に免疫化学的測定法等に用い
るのに十分な比活性があるＡＰを発現し得るものであれ
ば、いかなる動物種由来のものでも良い。例えば、大腸
菌由来のＡＰ（ＢＡＰ）のアミノ酸配列をコ−ドする遺
伝子でも良いが、十分な比活性を発揮し得るという観点
からは、牛小腸由来又はヒト小腸由来のＡＰのアミノ酸
配列をコ−ドする遺伝子が特に好ましい。Further, the present invention is obtained by culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following two kinds of genes. An immunochemical assay kit containing a recombinant AP fusion protein. A first gene; including a gene encoding the amino acid sequence of an arbitrary protein or its derivative and a gene encoding the amino acid sequence of AP or its derivative downstream thereof, and expressing it as an arbitrary protein or its derivative Gene capable of expressing fusion protein with AP or its derivative Second gene; Gene encoding amino acid sequence of AP or its derivative The gene encoding the amino acid sequence of AP used in the present invention is It may be derived from any animal species as long as it can express AP having a specific activity sufficient to be used for immunochemical assay etc. when expressed. For example, a gene encoding the amino acid sequence of Escherichia coli-derived AP (BAP) may be used, but from the viewpoint of exhibiting sufficient specific activity, the amino acid sequence of AP derived from bovine small intestine or human small intestine is encoded. The gene to be added is particularly preferable.

【００２０】本発明で使用するＡＰのアミノ酸配列をコ
−ドする遺伝子は、天然のアミノ酸配列に１以上のアミ
ノ酸残基が付加され、天然のアミノ酸配列の１以上のア
ミノ酸残基が欠損し又は天然のアミノ酸配列の１以上の
アミノ酸残基が他のアミノ酸残基に置換された、いわゆ
る誘導体であっても良い。The gene coding for the amino acid sequence of AP used in the present invention has one or more amino acid residues added to the natural amino acid sequence, and has one or more amino acid residues deleted from the natural amino acid sequence. It may be a so-called derivative in which one or more amino acid residues in the natural amino acid sequence are replaced with other amino acid residues.

【００２１】本発明で、ＡＰと融合させるタンパク質
は、それ自身の遺伝子工学的な発現が公知であるタンパ
ク質であれば特に制限はない。従って本発明では、これ
らの天然のアミノ酸配列や、天然のアミノ酸配列に１以
上のアミノ酸残基が付加され、天然のアミノ酸配列の１
以上のアミノ酸残基が欠損し又は天然のアミノ酸配列の
１以上のアミノ酸残基が他のアミノ酸残基に置換され
た、いわゆる誘導体をコ−ドする遺伝子を使用すれば良
い。In the present invention, the protein to be fused with AP is not particularly limited as long as it is a protein whose expression by genetic engineering is known. Therefore, in the present invention, these natural amino acid sequences or one or more amino acid residues added to the natural amino acid sequence are used to
A gene coding for a so-called derivative in which the above amino acid residues are deleted or one or more amino acid residues in the natural amino acid sequence are replaced with other amino acid residues may be used.

【００２２】この様なタンパク質として、具体的に抗体
を例示することができる。使用する遺伝子により発現さ
れる抗体は、いかなる抗原を認識する抗体でも良い。抗
体の由来についても種別に制限はないが、遺伝子レベル
の知見の多い、マウスやヒト由来の抗体が特に好まし
い。抗体の形態については、天然のＩｇＧ型、Ｆａｂ
型、Ｆｖ型又は一本鎖Ｆｖ型等、特に制限はない。Specific examples of such a protein include an antibody. The antibody expressed by the gene used may be an antibody that recognizes any antigen. The origin of the antibody is not limited to any particular type, but an antibody of mouse or human origin, which has many gene-level findings, is particularly preferable. As for the form of the antibody, a natural IgG type, Fab
Type, Fv type, single chain Fv type, etc. are not particularly limited.

【００２３】通常、モノクロ−ナル抗体は、抗原感作マ
ウスの脾臓細胞とミエロ−マ細胞の融合体であるハイブ
リド−マを作製し、該ハイブリド−マの産生物として調
製される。このようなハイブリド−マから抗体遺伝子を
単離する場合には、ゲノム遺伝子から単離する方法
（例：T. Kaneko ら、J. Biochemistry, 113, p114, 19
93年参照）やmRNAから単離する方法（ファルマシア製キ
ット）が知られており、どのような方法でも良い。Usually, a monoclonal antibody is prepared as a product of a hybridoma, which is a fusion of spleen cells and myeloma cells of an antigen-sensitized mouse. When an antibody gene is isolated from such a hybridoma, a method of isolating it from a genomic gene (eg, T. Kaneko et al., J. Biochemistry, 113, p114, 19).
(See 1993) and methods for isolating from mRNA (Pharmacia kit) are known, and any method may be used.

【００２４】抗体活性の発現のためには、Ｈ鎖及びＬ鎖
が必要であるため、上記本発明の組換えＡＰ融合抗体製
造用ベクタ−においては、少なくとも前記第１〜３の遺
伝子が必要である。従って本発明の組換えＡＰ融合抗体
製造用の単一発現ベクタ−又は複数の発現ベクタ−のセ
ットは、第１の遺伝子（抗体のＨ鎖Ｖ及びＣＨ１領域、
又はその誘導体のアミノ酸配列をコ−ドする遺伝子）、
第２の遺伝子（抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子）及び第３の遺伝子（ＡＰ又はそ
の誘導体のアミノ酸配列をコ−ドする遺伝子）を含有す
るものである。なお、第１の遺伝子又は第２の遺伝子の
いずれか一方は、更にその下流にＡＰ又はその誘導体の
アミノ酸配列をコ−ドする遺伝子を含み、その発現によ
り抗体のＨ鎖Ｖ及びＣＨ１領域、又はその誘導体とＡＰ
又はその誘導体との融合タンパク質か、あるいは、抗体
のＬ鎖又はその誘導体とＡＰ又はその誘導体との融合タ
ンパク質を発現し得るものである。Since H chain and L chain are required for expression of antibody activity, at least the first to third genes are required in the above-mentioned vector for producing recombinant AP fusion antibody of the present invention. is there. Therefore, the set of a single expression vector or a plurality of expression vectors for producing the recombinant AP fusion antibody of the present invention comprises the first gene (H chain V and CH1 regions of the antibody,
Or a gene encoding the amino acid sequence of its derivative),
It contains a second gene (a gene encoding the amino acid sequence of the antibody L chain or its derivative) and a third gene (a gene encoding the amino acid sequence of AP or its derivative). Either the first gene or the second gene further contains a gene coding the amino acid sequence of AP or a derivative thereof in the downstream thereof, and its expression causes the H chain V and CH1 regions of the antibody, or Derivatives and AP
Or a fusion protein with a derivative thereof, or a fusion protein with an antibody L chain or a derivative thereof and AP or a derivative thereof.

【００２５】このことは、即ち、単一のベクタ−であれ
ば上記第１〜３の遺伝子の全てを含有していることを意
味し、また複数（２又は３）のベクタ−であれは、例え
ば上記第１の遺伝子を含むものと第２及び３の遺伝子を
含むものの２つのベクタ−のセットや、それぞれ遺伝子
を含む３つのベクタ−のセット等が例示できる。This means that a single vector contains all of the above-mentioned first to third genes, and a plurality of vectors (2 or 3), For example, a set of two vectors, one containing the first gene and one containing the second and third genes, a set of three vectors each containing the gene, and the like can be exemplified.

【００２６】一方、本発明の組換えＡＰ融合タンパク質
製造用の単一発現ベクタ−又は複数の発現ベクタ−のセ
ットは、第１の遺伝子（任意のタンパク質又はその誘導
体のアミノ酸配列をコ−ドする遺伝子とその下流のＡＰ
又はその誘導体のアミノ酸配列をコ−ドする遺伝子を含
み、その発現により任意のタンパク質又はその誘導体と
ＡＰ又はその誘導体との融合タンパク質を発現し得る遺
伝子）及び第２の遺伝子（ＡＰ又はその誘導体のアミノ
酸配列をコ−ドする遺伝子）を含有するものである。従
って、単一のベクタ−であれば上記第１及び２の遺伝子
の全てを含有していることを意味し、また複数（２）の
ベクタ−であれは、上記第１の遺伝子を含むものと第２
の遺伝子を含むものの２つのベクタ−のセットである。On the other hand, the single expression vector or the set of plural expression vectors for producing the recombinant AP fusion protein of the present invention encodes the amino acid sequence of the first gene (arbitrary protein or its derivative). Gene and AP downstream
Or a gene containing a gene encoding the amino acid sequence of its derivative, and capable of expressing a fusion protein of any protein or its derivative with AP or its derivative by its expression) and a second gene (of AP or its derivative) It contains a gene encoding an amino acid sequence). Therefore, it means that a single vector contains all of the above-mentioned first and second genes, and a plurality (2) of vectors contains the above-mentioned first gene. Second
Is a set of two vectors containing the genes of.

【００２７】本発明の組換えＡＰ融合抗体製造用の発現
ベクタ−において、第３のＡＰ遺伝子に加え、第１の遺
伝子又は第２の遺伝子のいずれか一方の下流に、ＡＰ又
はその誘導体のアミノ酸配列をコ−ドする遺伝子を含有
させ、その発現により抗体のＨ鎖Ｖ及びＣＨ１領域、又
はその誘導体とＡＰ又はその誘導体との融合タンパク質
か、あるいは、抗体のＬ鎖又はその誘導体とＡＰ又はそ
の誘導体との融合タンパク質を発現し得る様にしたの
は、抗体のアミノ酸配列と融合したＡＰと融合していな
い遊離のＡＰの２種類を発現させ、ＡＰが抗体と融合し
た状態でより高活性を発揮する２量体として存在させる
ためである。この様な意味においても、特にＡＰは、そ
の２量体化が阻害されない範囲であれば、前記のごとく
誘導体化されていても良い。In the expression vector for producing the recombinant AP fusion antibody of the present invention, in addition to the third AP gene, the amino acid of AP or its derivative is provided downstream of either the first gene or the second gene. A fusion protein comprising an antibody H chain V and CH1 region or a derivative thereof and AP or a derivative thereof by containing a gene encoding a sequence, or an antibody L chain or a derivative thereof and AP or its It was made possible to express a fusion protein with a derivative by expressing two types of AP, which is an amino acid sequence of an antibody, fused AP and unfused free AP, and shows higher activity in the state where AP is fused with an antibody. This is because it exists as a dimer that exerts its effect. Even in this sense, AP may be derivatized as described above, as long as the dimerization is not inhibited.

【００２８】なお発現ベクタ−は、前記の遺伝子を発現
させるためのＤＮＡ配列を有し、後記のごとき宿主細胞
を形質転換できるものであれば、特に制限はない。遺伝
子を発現させるためのＤＮＡ配列としては、プロモ−タ
−系が重要であり、乳糖プロモ−タ−系、トリプトファ
ンプロモ−タ−系、ＧＡＬ４プロモ−タ−系、ＳＶ４０
プロモ−タ−系又はアデノウイルスプロモ−タ−系等が
例示できるが、宿主細胞との関係において適宜選定すれ
ば良い。またこれらのベクタ−は、選定された宿主細胞
を形質転換する操作にあたり、ベクタ−が導入されなか
った宿主と導入された宿主との選別を可能にするため、
例えば、ネオマイシン等の薬剤に対する耐性を宿主細胞
に付与するためのＤＮＡ配列（いわゆるマ−カ−ＤＮ
Ａ）を含んでいることが望ましい。The expression vector is not particularly limited as long as it has a DNA sequence for expressing the above gene and can transform a host cell as described below. As a DNA sequence for expressing a gene, a promoter system is important, and a lactose promoter system, a tryptophan promoter system, a GAL4 promoter system, SV40.
Examples thereof include a promoter system and an adenovirus promoter system, which may be appropriately selected in relation to the host cell. Further, these vectors, in the operation of transforming the selected host cells, to allow selection of the host into which the vector was not introduced and the host into which the vector was introduced,
For example, a DNA sequence for imparting resistance to a host cell to a drug such as neomycin (so-called marker DN).
It is desirable to include A).

【００２９】本発明の組換えＡＰ融合抗体又はＡＰ融合
タンパク質の製造方法は、前記したような単一の発現用
ベクタ−及び／又は複数の発現ベクタ−のセットで形質
転換した宿主細胞を培養し、培養物から前記遺伝子の発
現物を取得することを特徴とする。当然のことながら、
本発明の単一の発現用ベクタ−と複数の発現ベクタ−の
セットは、同時に使用することも可能である。The method for producing the recombinant AP fusion antibody or AP fusion protein of the present invention comprises culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors as described above. And obtaining an expression product of the gene from a culture. As a matter of course,
The set of a single expression vector and a plurality of expression vectors of the present invention can be used simultaneously.

【００３０】単一の発現用ベクタ−を用いる場合には、
単にそれを用いて適当な宿主細胞を形質転換すれば良い
が、複数の発現ベクタ−のセットを用いる場合には、そ
れらベクタ−の全てを宿主細胞に導入することが必要と
なるため、全ベクタ−による形質転換の有無確認作業の
ため、各ベクタ−に異なるマ−カ−ＤＮＡを導入してお
くことが好ましい。When a single expression vector is used,
It suffices to simply transform an appropriate host cell using it. However, when using a set of a plurality of expression vectors, it is necessary to introduce all of these vectors into the host cell. It is preferable to introduce a different marker DNA into each vector in order to confirm the presence or absence of transformation by-.

【００３１】使用する宿主細胞としては、例えば大腸
菌、酵母、枯草菌又は培養細胞等が例示できる。特に培
養細胞としては、例えばＣＯＳ細胞（猿の腎臓繊維芽細
胞）、ＣＨＯ細胞（チャイニ−ズハムスタ−の卵巣細
胞）、Ｃ１２７細胞（マウス癌細胞）を例示することが
できる。Examples of host cells used include Escherichia coli, yeast, Bacillus subtilis, cultured cells and the like. In particular, examples of the cultured cells include COS cells (monkey kidney fibroblasts), CHO cells (chinese hamster ovary cells), and C127 cells (mouse cancer cells).

【００３２】以上の様にして形質転換した宿主細胞を、
当該宿主細胞に適した培地で培養することにより、組換
えＡＰ融合抗体又は組換えＡＰ融合タンパク質を製造す
ることができる。製造された組換えＡＰ融合抗体又は組
換えＡＰ融合タンパク質は、特に免疫化学的測定方法に
好適である。The host cell transformed as described above is
Recombinant AP fusion antibody or recombinant AP fusion protein can be produced by culturing in a medium suitable for the host cell. The produced recombinant AP fusion antibody or recombinant AP fusion protein is particularly suitable for an immunochemical assay method.

【００３３】即ち、遺伝子工学的に製造された、均一な
性質、免疫測定に十分なＡＰ活性及び通常の抗体活性を
有する組換えＡＰ融合抗体は、例えば従来のサンドイッ
チ免疫測定法等における標識抗体として使用することが
可能であり、その均一性に由来して従来より高感度化、
高精度化を図ることができる。また同様に均一な性質、
免疫測定に十分なＡＰ活性及び通常の抗体活性を有する
組換えＡＰ融合タンパク質は、例えば従来の競合的免疫
測定法等における標識抗原として使用することが可能で
あり、その均一性に由来して従来より高感度化、高精度
化を図ることができる。That is, a recombinant AP fusion antibody produced by genetic engineering and having uniform properties, sufficient AP activity for immunoassay and ordinary antibody activity is used as a labeled antibody in, for example, a conventional sandwich immunoassay. It is possible to use, and due to its uniformity, higher sensitivity than before,
Higher accuracy can be achieved. Also with uniform properties,
A recombinant AP fusion protein having sufficient AP activity for immunoassay and ordinary antibody activity can be used as a labeled antigen in, for example, a conventional competitive immunoassay method, and has been conventionally used because of its homogeneity. Higher sensitivity and higher accuracy can be achieved.

【００３４】[0034]

【実施例】以下に本発明をさらに詳細に説明するために
実施例を示すが、本発明はこれら実施例に限定されるも
のではない。なお、実施例の記載に当たり、配列表に記
載したＤＮＡの塩基配列を引用するが、配列番号１はプ
ラスミドｐＨＩＰのヒトＡＰ（本実施例においては、以
下「ｈＩＰ」と略する）をコ−ドする部分の塩基配列と
推定されるアミノ酸配列とを示し、配列番号２はヒトＩ
ｇＧのコンスタント領域をコ−ドするゲノム遺伝子の、
イントロンを含む塩基配列と推定されるアミノ酸配列を
示し、配列番号３はプラスミドｐＶＰ５の融合抗体をコ
−ドする部分のイントロンを含む塩基配列と推定される
アミノ酸配列を示し、配列番号４はプラスミドｐＶＰ３
の融合抗体をコ−ドする部分のイントロンを含む塩基配
列と推定されるアミノ酸配列を示し、配列番号５はプラ
スミドｐＺＰ１の融合抗体をコ−ドする部分のイントロ
ンを含む塩基配列と推定されるアミノ酸配列を示し、配
列番号６はプラスミドｐＺＰ２の融合抗体をコ−ドする
部分のイントロンを含む塩基配列と推定されるアミノ酸
配列を示し、配列番号７はプラスミドｐＸＰＣの融合抗
体と選択遺伝子Ｅｃｏｇｐｔをコ−ドする部分のイント
ロン及びノンコ−ディング領域を含む塩基配列と推定さ
れるアミノ酸配列を示し、配列番号８はプラスミドｐＸ
ＰＤの融合抗体と選択遺伝子Ｅｃｏｇｐｔをコ−ドする
部分のイントロン及びノンコ−ディング領域を含む塩基
配列と推定されるアミノ酸配列を示し、配列番号９はプ
ラスミドｐＸＰＥの融合抗体と選択遺伝子Ｅｃｏｇｐｔ
をコ−ドする部分のイントロン及びノンコ−ディング領
域を含む塩基配列と推定されるアミノ酸配列を示し、配
列番号１０はプラスミドｐＣＨＩＰ１の融合抗体をコ−
ドする部分のイントロンを含む塩基配列と推定されるア
ミノ酸配列を示す。EXAMPLES Examples will be shown below to explain the present invention in more detail, but the present invention is not limited to these examples. In the description of the examples, the nucleotide sequences of the DNAs listed in the sequence listing are cited, but SEQ ID NO: 1 is a code for human AP of plasmid pHIP (hereinafter, abbreviated as “hIP” in this example). Shows the nucleotide sequence of the portion of the amino acid sequence and the deduced amino acid sequence.
of the genomic gene encoding the constant region of gG,
The amino acid sequence deduced to be a nucleotide sequence containing an intron is shown, and SEQ ID NO: 3 is an amino acid sequence deduced to be a nucleotide sequence containing an intron of a portion encoding a fusion antibody of plasmid pVP5, and SEQ ID NO: 4 is a plasmid pVP3.
Shows an amino acid sequence deduced to be a nucleotide sequence containing the intron of the portion encoding the fusion antibody of SEQ ID NO: 5, and SEQ ID NO: 5 is an amino acid deduced to be the nucleotide sequence containing the intron of the portion encoding the fusion antibody of plasmid pZP1. SEQ ID NO: 6 shows the amino acid sequence deduced to be the nucleotide sequence containing the intron of the portion encoding the fusion antibody of plasmid pZP2, and SEQ ID NO: 7 shows the fusion antibody of plasmid pXPC and the selection gene Ecogpt. Shows an amino acid sequence deduced to be a nucleotide sequence containing an intron and a non-coding region of the coding region, and SEQ ID NO: 8 is a plasmid pX.
A fusion antibody of PD and an amino acid sequence deduced to be a nucleotide sequence including an intron and a noncoding region of a portion encoding the selection gene Ecogpt are shown. SEQ ID NO: 9 is a fusion antibody of plasmid pXPE and a selection gene Ecogpt.
Shows an amino acid sequence deduced to be a nucleotide sequence containing an intron and a non-coding region of the region encoding SEQ. NO .: 10 is a fusion antibody of plasmid pCHIP1.
The amino acid sequence presumed to be the nucleotide sequence containing the intron of the region to be added is shown.

【００３５】実施例１．アルカリ・フォスファタ−ゼ融
合抗体ベクタ−の作製 以下の方法により、ヒト抗体Ｈ鎖コンスタント領域をコ
−ドするゲノム遺伝子のｈｉｎｇｅ、ＣＨ２及びＣＨ３
領域のＣ末端側にｈＩＰ遺伝子が融合したプラスミドを
作成した。Example 1. Preparation of Alkaline-Phosphatase Fusion Antibody Vector By the following method, the hinge genes, CH2 and CH3, of the genomic genes encoding the human antibody H chain constant region were coded.
A plasmid in which the hIP gene was fused to the C-terminal side of the region was prepared.

【００３６】塩基配列の決定にはシ−クエネ−ス・キッ
ト（ＵＳＢ社）を使用し、添付のマニュアルにしたがっ
て実験を行った。各スケ−ルでのプラスミドの調整は、
Ｍｏｌｅｃｕｌａｒ Ｃｌｏｎｉｎｇ（Ｔ．Ｍａｎｉａ
ｔｉｓら、Ｃｏｌｄ Ｓｐｒｉｎｇ Ｈａｒｂｏｒ刊）
にしたがった。The sequence sequence kit (USB company) was used to determine the nucleotide sequence, and the experiment was conducted according to the attached manual. Preparation of plasmids on each scale
Molecular Cloning (T. Mania
(published by tis et al., Cold Spring Harbor)
According to.

【００３７】ｈＩＰ遺伝子をクロ−ン化したプラスミド
ｐＨＩＰ（Ｈｉｇａｓｈｉｎｏら、Ｃｌｉｎｉｃａ Ｃ
ｈｉｍｉｃａ Ａｃｔａ、１８６、Ｐ１５１、１９８９
年参照。なお、ｐＨＩＰのＤＮＡ配列を配列表の配列番
号１に示す）より、ＰｖｕＩＩによる部分的切断後Ｓｐ
ｅＩリンカ−を連結することにより成熟ｈＩＰの第４番
目の残基もしくは第１７番目の残基の前にＳｐｅＩ部位
を導入しそれぞれｐＩＰ０２及びｐＩＰ０３とした。さ
らに、ＢｐｍＨＩによる切断、Ｔ４ ＤＮＡｐｏｌｙｍ
ｅｒａｓｅによる末端平滑化の後ＸｂａＩリンカ−を挿
入し、終止コドンを導入し、各リンカ−導入部位の塩基
配列を確認しそれぞれｐＩＰ１１及びｐＩＰ１３とし
た。A plasmid pHIP cloned from the hIP gene (Higasino et al., Clinica C
himica Acta, 186, P151, 1989
See year. The DNA sequence of pHIP is shown in SEQ ID NO: 1 of the sequence listing), showing that Spv after partial cleavage with PvuII.
An SpeI site was introduced in front of the 4th residue or the 17th residue of the mature hIP by ligating an eI linker to obtain pIP02 and pIP03, respectively. Furthermore, cleavage with BpmHI, T4 DNApolym
After blunting the ends with erase, an XbaI linker was inserted, a stop codon was introduced, the nucleotide sequences of the respective linker-introduced sites were confirmed, and they were designated as pIP11 and pIP13, respectively.

【００３８】ヒト抗体Ｈ鎖コンスタント領域をコ−ドす
るゲノム遺伝子をクロ−ン化したプラスミドｐＳＶ２−
ＨＧ１ｇｐｔ（特開平６−１５３９５５号参照。なお、
プラスミドのＤＮＡ配列を配列表に配列番号２として示
す）よりＣＨ１領域、ｈｉｎｇｅ、ＣＨ２（Ｎ末側）領
域を含む約１０６０塩基対のＳａｃＩＩ断片をｐＢｌｕ
ｅｓｃｒｉｐｔＩＩ（東洋紡（株）製）のＳａｃＩＩ部
位に挿入して得たプラスミドｐＹＰ０１に、５´−ＣＡ
ＧＣＡＣＣＴＧＡＧＣＴＣＣＴＧＧＧＧＧ−３´の配列
を有する合成ＤＮＡを作製し、部位特異的変異導入シス
テム（アマシャム製）を用いて、ＣＨ２領域にＳａｃＩ
部位を導入し、塩基配列を確認の後、プラスミドｐＹＰ
０９とした。Plasmid pSV2-cloned genomic gene coding for human antibody heavy chain constant region
HG1 gpt (see JP-A-6-153955.
The DNA sequence of the plasmid is shown in the sequence listing as SEQ ID NO: 2), and a SacII fragment of about 1060 base pairs including CH1 region, hinge, CH2 (N-terminal side) region is pBlue
5'-CA was added to plasmid pYP01 obtained by inserting it into the SacII site of escriptII (manufactured by Toyobo Co., Ltd.).
A synthetic DNA having the sequence of GCACCTGAGCTCCTGGGGG-3 'was prepared, and SacI was added to the CH2 region using a site-directed mutagenesis system (manufactured by Amersham).
After introducing the site and confirming the nucleotide sequence, plasmid pYP
It was set to 09.

【００３９】ＳａｃＩ部位の導入されたｐＹＰ０９の約
１０６０塩基対のＳａｃＩＩ断片をｐＳＶ２−ＨＧ１ｇ
ｐｔの対応する断片と交換してｐＹＰ１０を作製した。
ｐＵＣ１９のＳｓｐＩ部位にＥｃｏＲＩリンカ−を連結
し、ＥｃｏＲＩによる切断、連結により、部分欠失プラ
スミドｐＹＥ０１を作製した。さらにｐＹＥ０１のＥｃ
ｏＲＩ−ＰｖｕＩＩ間にｐＹＰ１０のヒト抗体Ｈ鎖コン
スタント領域を含む約２９００塩基対のＥｃｏＲＩ−Ｐ
ｖｕＩＩ断片を挿入し、ｐＹＥ０２を作製した。ｐＳＶ
２−ＨＧ１ｇｐｔをＢａｍＨＩ、ＰｖｕＩＩで切断後、
ｋｌｅｎｏｗ断片で末端平滑化して得られるＥ．ｃｏｌ
ｉ ｘａｎｔｈｉｎｅ−ｇｕａｎｉｎｅｐｈｏｓｐｈｏ
ｒｉｂｏｓｙｌｔｒａｎｓｆｅｒａｓｅ（Ｅｃｏｇｐ
ｔ）遺伝子を含む約２２００塩基対の断片をｐＹＥ０２
のＰｖｕＩＩ部位に挿入して、ｐＨＣＧ１を作製した。
ｐＨＣＧ１の概要を図１に、そのＤＮＡの塩基配列を配
列表の配列番号２に示す）。The SacII fragment of about 1060 base pairs of pYP09 having the SacI site introduced was transformed with pSV2-HG1g.
Replacement of the corresponding fragment of pt created pYP10.
An EcoRI linker was ligated to the SspI site of pUC19, and a partial deletion plasmid pYE01 was prepared by cutting with EcoRI and ligation. Furthermore, Ec of pYE01
EcoRI-P of about 2900 base pairs containing the human antibody heavy chain constant region of pYP10 between oRI-PvuII
The vuII fragment was inserted to create pYE02. pSV
After cutting 2-HG1gpt with BamHI and PvuII,
E. coli obtained by blunting the ends with the Klenow fragment. col
i xanthine-guaninephospho
ribosyltransferase (Ecogp
t) A fragment of about 2200 base pairs containing the gene was designated as pYE02.
Was inserted into the PvuII site of the gene to prepare pHCG1.
An outline of pHCG1 is shown in FIG. 1, and the nucleotide sequence of its DNA is shown in SEQ ID NO: 2 in the sequence listing).

【００４０】ｐＩＰ１１及びｐＩＰ１３のそれぞれをＳ
ｐｅＩ、ＥｃｏＲＩによる切断、ｋｌｅｎｏｗ断片によ
る末端平滑化して得られるｈＩＰ遺伝子を含むそれぞれ
約１４１０、１３７０塩基対の断片を、ｐＨＣＧ１をＳ
ａｃＩによる切断、Ｔ４ ＤＮＡ ｐｏｌｙｍｅｒａｓ
ｅにより末端平滑化した部位に挿入し、連結部位が正し
いフレ−ムで融合していることを確認してｐＶＰ５及び
ｐＶＰ３とした。これらの概要を図２又は３に、またこ
れらのＤＮＡの塩基配列を配列表の配列番号３又は４に
示す。Suppose each of pIP11 and pIP13
Approximately 1410 and 1370 base pair fragments containing the hIP gene obtained by digestion with peI and EcoRI and blunting the ends with the Klenow fragment, respectively, and pHCG1 into S
Cleavage with acI, T4 DNA polymers
It was inserted into the site blunted by e, and it was confirmed that the ligation site was fused with the correct frame, and designated as pVP5 and pVP3. An outline of these is shown in FIG. 2 or 3, and the nucleotide sequences of these DNAs are shown in SEQ ID NO: 3 or 4 of the sequence listing.

【００４１】ｐＩＰ１１及びｐＩＰ１３のそれぞれをＳ
ｐｅＩ、ＥｃｏＲＩによる切断、ｋｌｅｎｏｗ断片によ
る末端平滑化して得られるｈＩＰ遺伝子を含むそれぞれ
約１４１０、１３７０塩基対の断片を、ｐＨＣＧ１をＸ
ｍｎＩにより部分分解した部位に挿入し、連結部位が正
しいフレ−ムで融合していることを確認してｐＺＰ１及
びｐＺＰ２とした。これらの概要を図４又は５に、また
これらのＤＮＡの塩基配列を配列表の配列番号５又は６
に示す。Suppose each of pIP11 and pIP13
Approximately 1410 and 1370 base pair fragments containing the hIP gene obtained by digestion with peI and EcoRI and blunting the ends with the Klenow fragment, respectively, and pHCG1 with X.
It was inserted into the site partially digested with mnI, and it was confirmed that the ligation site was fused with the correct frame, and the plasmids were named pZP1 and pZP2. An outline of these is shown in FIG. 4 or 5, and the nucleotide sequences of these DNAs are shown in SEQ ID NO: 5 or 6 of the sequence listing.
Shown in

【００４２】ｐＨＣＧ１のＰｖｕＩＩ部位にＳｐｅＩリ
ンカ−を、ＣＨ３領域のＸｍｎＩ部位にＸｂａＩリンカ
−をそれぞれ挿入し、ｐＹＥ１４を作製した。ｐＩＰ１
１をＰｓｔＩ、ＸｂａＩによる切断をして得られるＨＩ
Ｐを含む約１３４０塩基対の断片を、ｐＹＥ１４のＰｓ
ｔＩ−ＸｂａＩ間に挿入し、ｐＹＥ１６を作製した。ｐ
ＳＶ２−ＨＧ１ｇｐｔをＢａｍＨＩ、ＨｉｎｄＩＩＩに
よる切断をして得られるＥｃｏｇｐｔ遺伝子を含む約２
０００塩基対の断片をｐＢｌｕｅｓｃｒｉｐｔＩＩに挿
入して、ｐＹＥ２８を作製した。ｐＹＥ２８をＢｇｌＩ
Ｉによる切断、Ｔ４ ＤＮＡ ｐｏｌｙｍｅｒａｓｅに
よる末端平滑化、ＳｐｅＩによる切断をして得られる約
１９００塩基対の断片を、ｐＹＥ１６をＸｂａＩによる
切断、末端平滑化、ＳｐｅＩによる切断をした間に挿入
し、ｐＹＥ２９を作製した。ｐＶＰ５をＰｓｔＩによる
切断をして得られる約２５０塩基対の断片をｐＹＥ２９
のＰｓｔＩ部位に挿入してｐＸＰＣを作製した。ｐＸＰ
Ｃの概要を図６に、またこのＤＮＡの塩基配列を配列表
の配列番号７に示す。A SpeI linker was inserted into the PvuII site of pHCG1 and an XbaI linker was inserted into the XmnI site of the CH3 region to prepare pYE14. pIP1
HI obtained by digesting 1 with PstI and XbaI
A fragment of about 1340 base pairs containing P was designated as Ps of pYE14.
It was inserted between tI and XbaI to prepare pYE16. p
About 2 containing the Ecogpt gene obtained by cleaving SV2-HG1gpt with BamHI and HindIII
The 000 base pair fragment was inserted into pBluescript II to create pYE28. pYE28 to BglI
A fragment of about 1900 base pairs obtained by digestion with I, blunting with T4 DNA polymerase and digestion with SpeI was inserted between pYE16 digested with XbaI, blunted and digested with SpeI to give pYE29. It was made. A fragment of about 250 base pairs obtained by digesting pVP5 with PstI was designated as pYE29.
Was inserted into the PstI site of pXPC to prepare pXPC. pXP
The outline of C is shown in FIG. 6, and the nucleotide sequence of this DNA is shown in SEQ ID NO: 7 in the sequence listing.

【００４３】下記の配列 ５´−ＣＣＣＡＡＧＧＡＣＧ
ＴＣＣＴＣＡＴＧＡＴＣ−３´を有する合成ＤＮＡを作
製し、部位特異的変異導入システム（アマシャム）を用
いて、ｐＹＰ０１にクロ−ン化されたＣＨ２領域にＡａ
ｔＩＩ部位を導入し、塩基配列を確認してｐＹＥ２３を
作製した。ｐＨＩＰよりＥｃｏＲＩ、ＢａｍＨＩによる
切断をして得られるｈＩＰのＮ末端部分を含む約３６０
塩基対の断片をｐＢｌｕｅｓｃｒｉｐｔＩＩに挿入し
て、ｐＹＥ２０を作製した。下記の配列 ５´−ＣＴＣ
ＴＣＣＣＴＧＧＡＣＧＴＣＡＴＣＣＣＡＧ−３´を有す
る合成ＤＮＡを作製し、部位特異的変異導入システム
（アマシャム）を用いて、ｐＹＥ２０にＡａｔＩＩ部位
を導入し、塩基配列を確認してｐＹＥ２４を作製した。
ｐＹＥ２４をＳａｃＩＩ、ＡａｔＩＩによる切断をして
得られる約１８０塩基対の断片を、ｐＹＥ２３のＳａｃ
ＩＩ、ＡａｔＩＩ部位間に挿入して、ｐＹＥ２５を作製
した。ｐＹＥ２５をＰｓｔＩによる切断して得られる約
３２０塩基対の断片をｐＹＥ２９のＰｓｔＩ部位に挿入
して、ｐＸＰＤを作製した。ｐＸＰＤの概要を図７に、
またこのＤＮＡの塩基配列を配列表の配列番号８に示
す。The following sequence 5'-CCCAAGGACG
A synthetic DNA having TCCTCATGATC-3 ′ was prepared, and a site-directed mutagenesis system (Amersham) was used to Aa the CH2 region cloned into pYP01.
The tII site was introduced, the nucleotide sequence was confirmed, and pYE23 was prepared. Approximately 360 including the N-terminal part of hIP obtained by digestion with pHRI with EcoRI and BamHI
The base pair fragment was inserted into pBluescript II to create pYE20. The following sequence 5'-CTC
A synthetic DNA having TCCCTGGACGTCATCCCAG-3 ′ was prepared, an AatII site was introduced into pYE20 using a site-directed mutagenesis system (Amersham), and the nucleotide sequence was confirmed to prepare pYE24.
A fragment of about 180 base pairs obtained by cleaving pYE24 with SacII and AatII was used as the Sac of pYE23.
It was inserted between the II and AatII sites to create pYE25. A fragment of about 320 base pairs obtained by cutting pYE25 with PstI was inserted into the PstI site of pYE29 to prepare pXPD. Figure 7 shows the outline of pXPD.
The base sequence of this DNA is shown in SEQ ID NO: 8 in the sequence listing.

【００４４】下記の２種類の配列を有する合成ＤＮＡ、
５´−ＣＧＧＴＧＧＣＧＧＣＧＧＴＴＣＡＧＧＣＧＧＴ
ＧＧＴＧＧＡＴＣＴＧＧＴＧＧＴＧＧＣＧＧＧＴＣＡＧ
ＡＣＧＴ−３´、５´−ＣＴＧＡＣＣＣＧＣＣＡＣＣＡ
ＣＣＡＧＡＴＣＣＡＣＣＡＣＣＧＣＣＴＧＡＡＣＣＧＣ
ＣＧＣＣＡＣＣＧＡＣＧＴ−３´を作製し、６５度で５
分間変性し、３７度で３０分間アニ−リングを行い、Ｔ
４ ｐｏｌｙｎｕｃｌｅｏｔｉｄｅ ｋｉｎａｓｅによ
り末端リン酸化したのち、ｐＹＥ２５のＡａｔＩＩ部位
に挿入して、ｐＹＥ２６を作製した。ｐＹＥ２６を塩基
配列確認の後ＰｓｔＩによる切断をして得られる約３６
０塩基対の断片を、ｐＹＥ２９のＰｓｔＩ部位に挿入し
て、ｐＸＰＥを作製した。ｐＸＰＥの概要を図８に、ま
たこのＤＮＡの塩基配列を配列表の配列番号９に示す。A synthetic DNA having the following two types of sequences,
5'-CGGTGGCGGGCGGTTCAGGGCGGT
GGTGGATCTGGGTGGTGGCGGGTCAG
ACGT-3 ', 5'-CTGACCCGCGCCACCA
CCAGATCCACCACCCGCCTGAACCGC
CGCCACCGACGT-3 'was made and the temperature was 5 degrees at 65 degrees.
Denature for 30 minutes, anneal at 37 degrees for 30 minutes, and
After terminal phosphorylation with 4 polynucleotide kinase, it was inserted into the AatII site of pYE25 to prepare pYE26. About 36 obtained by cleaving pYE26 with PstI after confirming the nucleotide sequence
The 0 base pair fragment was inserted into the PstI site of pYE29 to create pXPE. An outline of pXPE is shown in FIG. 8, and the nucleotide sequence of this DNA is shown in SEQ ID NO: 9 in the sequence listing.

【００４５】以下の２種類の配列を有する合成ＤＮＡ、
５´−ＧＡＧＣＣＣＡＡＡＴＶＴＴＧＴＧＧＴＧＧＣＧ
ＧＣＧＧＴＴＣＡＧＧＣＧＧＴＧＧＴＧＧＡＴＣＴＧＧ
ＴＧＧＴＧＧＣＧＧＧＡ−３´、５´−ＣＴＡＧＴＣＣ
ＣＧＣＣＡＣＣＡＣＣＡＧＡＴＣＣＡＣＣＡＣＣＧＣＣ
ＴＧＡＡＣＣＧＣＣＧＣＣＡＣＣＡＣＡＡＧＡＴＴＴＧ
ＧＧＣＴＣＴＧＣＡ−３´を作製し６５度で５分間変性
し、３７度で３０分間アニ−リングを行い、Ｔ４ ｐｏ
ｌｙｎｕｃｌｅｏｔｉｄｅ ｋｉｎａｓｅにより末端リ
ン酸化したのち、ｐＢｌｕｅｓｃｒｉｐｔＩＩのＰｓｔ
Ｉ−ＳｐｅＩ部位間に挿入し、ｐＢＫＳＭ−Ｌｉｎｋｅ
ｒを作製し、塩基配列の確認を行った。ｐＨＣＧ１のＥ
ｃｏＲＩ、ＰｓｔＩによる切断によって得られるＣＨ１
領域をコ−ドする約９００塩基対の断片をｐＢＫＳＭ−
ＬｉｎｋｅｒのＥｃｏＲＩ−ＰｓｔＩ部位に挿入してｐ
ＢＫＳＭ−ＣＨ１Ｌｉｎｋｅｒを作製した。ｐＥＣＥｄ
ｈｆｒ（Ｙａｓｕｋａｗａら、Ｊ．Ｂｉｏｃｈｅｍ、１
０８巻、ｐ６７３、１９９０年参照）のＢａｍＨＩ切
断、末端平滑化、ＸｂａＩ切断して得られるＳＶ４０ｐ
ｏｌｙａｄｅｎｙｌａｔｉｏｎ ｓｉｇｎａｌをコ−ド
する断片をｐＢｌｕｅｓｃｒｉｐｔＩＩのＳａｃＩ切
断、末端平滑化、ＸｂａＩ切断して得られる部位間に挿
入し、ｐＢＫＳＭ−ｐｏｌｙＡを作製した。ｐＩＰ１３
をＳｐｅＩ、ＸｂａＩ切断して得られるｈＩＰをコ−ド
する断片を、ｐＢＫＳＭ−ｐｏｌｙＡのＳｐｅＩ、Ｘｂ
ａＩ部位間に挿入し、ｈＩＰをコ−ドする遺伝子の３´
末端側にＳＶ４０ ｐｏｌｙａｄｅｎｙｌａｔｉｏｎ
ｓｉｇｎａｌを有するｐＢＫＳＭ−ＨＩＰｐｏｌｙＡを
作製した。ｐＢＫＳＭ−ＣＨ１ＬｉｎｋｅｒをＥｃｏＲ
Ｉ、ＳｐｅＩ切断して得られる断片をｐＢＫＳＭ−ＨＩ
ＰｐｏｌｙＡのＥｃｏＲＩ、ＳｐｅＩ部位間に挿入して
ｐＣＨＩＰ１を作製した。ｐＣＨＩＰ１の概要を図９
に、またこのＤＮＡの塩基配列を配列表の配列番号１０
に示す。Synthetic DNA having the following two kinds of sequences,
5'-GAGCCCAAATVTTGTGGGTGGGCG
GCGGTTCAGGCGGGTGGTGGATCTGG
TGGTGGGCGGGA-3 ', 5'-CTAGTCC
CGCCACCACCAGATCCACCACCCGCC
TGAACCGCCGCCACCACAAGATTTG
GGCTCTGCA-3 ′ was prepared, denatured at 65 ° C. for 5 minutes, annealed at 37 ° C. for 30 minutes, and then T4 po
After terminal phosphorylation by nucleotide kinase, Pst of pBluescript II
Inserted between I-SpeI sites, pBKSM-Linke
r was prepared and the nucleotide sequence was confirmed. E of pHCG1
CH1 obtained by digestion with coRI and PstI
A fragment of about 900 base pairs coding for the region was designated as pBKSM-
P was inserted into the EcoRI-PstI site of the Linker.
BKSM-CH1Linker was produced. pECED
hfr (Yasukawa et al., J. Biochem, 1
Sv40p obtained by BamHI digestion, end blunting, and XbaI digestion (see Vol. 08, p673, 1990).
The fragment encoding the oleadenylation signal was inserted between the sites obtained by digesting pBluescript II with SacI, blunting the ends and digesting with XbaI to prepare pBKSM-polyA. pIP13
Was digested with SpeI and XbaI to obtain a fragment encoding hIP, which was designated as SpeI and Xb of pBKSM-polyA.
3'of the gene inserted between aI sites and coding for hIP
SV40 polyadenylation on the terminal side
pBKSM-HIPpolyA having a signal was prepared. pBKSM-CH1Linker EcoR
The fragment obtained by digesting with I and SpeI was designated as pBKSM-HI.
It was inserted between the EcoRI and SpeI sites of PpolyA to prepare pCHIP1. Figure 9 shows an overview of pCHIP1.
In addition, the base sequence of this DNA is SEQ ID NO: 10 in the sequence listing.
Shown in

【００４６】実施例２．発現ベクタ−の作製 ｐＶＰ３のＥｃｏＲＩ部位に、ｐＢＬＵＥ／ＨＥ７（特
開平６−１５３９５５号参照）のＨ鎖可変領域を含む約
３０００塩基対のＥｃｏＲＩ断片を挿入し、ｐＶＰ３−
Ｈ１８Ａを作製した。同様にして、ｐＶＰ５、ｐＺＰ
１、ｐＺＰ２を元にして、ｐＶＰ５−Ｈ１８Ａ、ｐＺＰ
１−Ｈ１８Ａ、ｐＺＰ２−Ｈ１８Ａを作製した。ｐＶＰ
３−Ｈ１８Ａの概要を図１０に示す。Example 2. Preparation of Expression Vector An EcoRI fragment of about 3000 base pairs containing the heavy chain variable region of pBLUE / HE7 (see Japanese Patent Laid-Open No. 6-153955) was inserted into the EcoRI site of pVP3, and pVP3-
H18A was produced. Similarly, pVP5 and pZP
1, based on pZP2, pVP5-H18A, pZP
1-H18A and pZP2-H18A were produced. pVP
An outline of 3-H18A is shown in FIG.

【００４７】ｐＸＰＣのＥｃｏＲＩ部位に、ｐＴＺ−Ｔ
Ｈ８Ｅ（特願平５−１５６７０７）のＨ鎖可変領域を含
む約４１００塩基対のＥｃｏＲＩ断片を挿入し、ｐＸＰ
Ｃ−ＴＳＨを作製した。。同様にして、それぞれｐＸＰ
Ｄ、ｐＸＰＥ、ｐＣＨＩＰ１を元として、ｐＸＰＤ−Ｔ
ＳＨ、ｐＸＰＥ−ＴＳＨ、ｐＣＨＩＰ１−ＴＨ８Ｅを作
製した。At the EcoRI site of pXPC, pTZ-T
An EcoRI fragment of about 4100 base pairs containing the H chain variable region of H8E (Japanese Patent Application No. 5-156707) was inserted into pXP
C-TSH was produced. . Similarly, pXP
Based on D, pXPE, and pCHIP1, pXPD-T
SH, pXPE-TSH, pCHIP1-TH8E were prepared.

【００４８】実施例３．アルカリ・フォスファタ−ゼ融
合抗体発現細胞の作製 マウス・ミエロ−マ細胞ＳＰ２／０を１０％のウシ胎児
血清（ＦＣＳ）を含むＤＭＥＭ培地中で対数増殖期中期
（約３から６×１０⁵個／ｍｌ）まで増殖させ、これを
ＰＢＳを用いて２回洗浄した。細胞２×１０⁷個と、ｐ
ＶＰ５−Ｈ１８Ａ、ｐＳＶ２−ＨＣκｎｅｏ／ＨＨγ３
（特開平６−１５３９５５号参照）、ｐＥＣＥｄｈｆｒ
−ＩＰ４７５（特願平５−７６８８３号）の３種のプラ
スミドそれぞれ３０μｇを８００μｌのＰＢＳに懸濁
し、５分間氷上で冷却した。ＧｅｎｅＰｕｌｓｅｒ（バ
イオラッド製）を用いて２５μファラッド、１０００ボ
ルトの条件で電気パルスをかける事により形質転換を行
った。さらに、５分間の氷上での冷却の後、ＤＭＥＭ−
１０％ＦＣＳ培地２０ｍｌに懸濁し、２日間培養した。
培地をｎｅｏ遺伝子の選択培地、すなわち８００μｇ／
ｍｌのＧ４１８（ギブコ）を含むＤＭＥＭ−１０％ＦＣ
Ｓ培地２０ｍｌに交換し、９６穴プレ−トにまいた。約
３週間後、コロニ−の成長を確認し、Ｅｃｏｇｐｔ遺伝
子の選択培地、２μｇ／ｍｌのミコフェノ−ル酸と７０
μｇ／ｍｌのキサンチンを含むＤＭＥＭ−１０％ＦＣＳ
培地に交換した。約１週間後十分な細胞の成長を確認し
て、アルカリ・フォスファタ−ゼ融合抗体の検出を行っ
た。Example 3. Preparation of Alkaline-Phosphatase Fusion Antibody-Expressing Cells Mouse myeloma cells SP2 / 0 were cultured in DMEM medium containing 10% fetal calf serum (FCS) in the mid-logarithmic growth phase (about 3 to 6 × 10 ⁵ cells / ml), which was washed twice with PBS. 2 × 10 ⁷ cells and p
VP5-H18A, pSV2-HCκneo / HHγ3
(See JP-A-6-153955), pECEdhfr
30 μg of each of three types of plasmids —IP475 (Japanese Patent Application No. 5-76883) was suspended in 800 μl of PBS, and cooled on ice for 5 minutes. Transformation was performed using GenePulser (manufactured by Bio-Rad) by applying an electric pulse under the conditions of 25 μfarad and 1000 V. Further, after cooling on ice for 5 minutes, DMEM-
The cells were suspended in 20 ml of 10% FCS medium and cultured for 2 days.
The medium is a neo gene selection medium, ie, 800 μg /
DMEM-10% FC with ml G418 (Gibco)
The medium was replaced with 20 ml of S medium and seeded on a 96-well plate. After about 3 weeks, growth of colonies was confirmed, and Ecogpt gene selection medium, 2 μg / ml of mycophenolic acid and 70% of the medium were used.
DMEM-10% FCS containing μg / ml xanthine
The medium was replaced. After about 1 week, sufficient cell growth was confirmed and the alkaline phosphatase fusion antibody was detected.

【００４９】ＥＬＩＳＡ用９６穴プレ−トにヒトＩｇＧ
のＦ（ａｂ´）₂に特異的な２．５μｇ／ｍｌの抗体を
各ウエル１００μｌずつ分注し、２時間以上室温で固定
化した。ＰＢＳにて洗浄後０．５％ＢＳＡを含むＰＢＳ
を各ウエル２００μｌずつ分注し、室温で２時間以上ブ
ロッキングを行った。ＰＢＳにて洗浄後、前記の細胞培
養上清１００μｌを入れ、室温で２時間放置した。ＰＢ
Ｓにて洗浄後、２μｇ／ｍｌのパラニトロフェニルリン
酸を含む１Ｍジエタノ−ルアミン−１ｍＭ ＭｇＣｌ₂
（ｐＨ９．８）を各ウエル１００μｌずつ分注し室温に
て発色させ、４０５ｎｍの吸光度を測定した。Human IgG on 96-well plate for ELISA
100 μl of each well of 2.5 μg / ml antibody specific for F (ab ′) ₂ was dispensed and immobilized at room temperature for 2 hours or more. After washing with PBS, PBS containing 0.5% BSA
Each well was dispensed in an amount of 200 μl and blocked at room temperature for 2 hours or more. After washing with PBS, 100 μl of the above cell culture supernatant was added and left at room temperature for 2 hours. PB
After washing with S, 1 M diethanolamine-1 mM MgCl ₂ containing ₂ μg / ml para-nitrophenyl phosphate
100 μl of (pH 9.8) was dispensed into each well, color was developed at room temperature, and the absorbance at 405 nm was measured.

【００５０】同様に、ＥＬＩＳＡ用９６穴プレ−トにヒ
トκＬ鎖に特異的な２．５μｇ／ｍｌの抗体を各ウエル
１００μｌずつ分注し、２時間以上室温で固定化した。
ＰＢＳにて洗浄後０．５％ＢＳＡを含むＰＢＳを各ウエ
ル２００μｌずつ分注し、室温で２時間以上ブロッキン
グを行った。ＰＢＳにて洗浄後、前期の細胞培養上清１
００μｌを入れ、室温で２時間放置した。ＰＢＳにて洗
浄後、２μｇ／ｍｌのパラニトロフェニルリン酸を含む
１Ｍジエタノ−ルアミン−１ｍＭ ＭｇＣｌ₂（ｐＨ
９．８）を各ウエル１００μｌずつ分注し室温にて発色
させ、４０５ｎｍの吸光度を測定した。Similarly, to the 96-well plate for ELISA, 2.5 μg / ml of an antibody specific for human κ L chain was dispensed in an amount of 100 μl / well and immobilized at room temperature for 2 hours or more.
After washing with PBS, 200 μl of PBS containing 0.5% BSA was dispensed in each well, and blocking was performed at room temperature for 2 hours or more. After washing with PBS, the cell culture supernatant 1 from the previous period
00 μl was added and left at room temperature for 2 hours. After washing with PBS, 1 M diethylamine-1 mM MgCl ₂ (pH containing ₂ μg / ml para-nitrophenyl phosphate)
9.8) was dispensed into each well by 100 μl, color was developed at room temperature, and the absorbance at 405 nm was measured.

【００５１】上記２種の測定法で顕著なアルカリ・フォ
スファタ−ゼ活性を示した細胞について常法によるクロ
−ニングを２回行った。すなわち、各ウエルに平均１個
の細胞が入る濃度に細胞を選択培地にて希釈して９６穴
プレ−トに分注した。２から３週間後に十分な増殖を確
認した後上記の方法にてアルカリ・フォスファタ−ゼ活
性を測定し、顕著なアルカリ・フォスファタ−ゼ活性を
示した細胞を再度、各ウエルに平均１個の細胞が入る濃
度に細胞を選択培地にて希釈して９６穴プレ−トに分注
した。この様にして、アルカリ・フォスファタ−ゼ融合
抗体を発現する細胞Ｈ１８Ａ・ＶＰ５ＩＰ−３を作成し
た。The cells showing remarkable alkaline phosphatase activity by the above-mentioned two measuring methods were subjected to conventional cloning twice. That is, the cells were diluted with a selective medium to a concentration such that an average of one cell was in each well, and the cells were dispensed into a 96-well plate. After confirming sufficient proliferation after 2 to 3 weeks, the alkaline phosphatase activity was measured by the above-mentioned method, and the cells showing remarkable alkaline phosphatase activity were re-administered to an average of 1 cell in each well. The cells were diluted with a selective medium to a concentration allowing to be dispensed into 96-well plates. In this manner, a cell H18A.VP5IP-3 expressing the alkaline phosphatase fusion antibody was prepared.

【００５２】同様にして、それぞれｐＶＰ３−Ｈ１８
Ａ、ｐＺＰ１−Ｈ１８Ａ、ｐＺＰ２−Ｈ１８Ａ、を用い
て融合抗体を発現する細胞を樹立した。Similarly, pVP3-H18
A, pZP1-H18A, pZP2-H18A were used to establish cells expressing the fusion antibody.

【００５３】同様にして、ｐＸＰＤ−ＴＳＨ、ｐＳＶ２
−ＨＣκｎｅｏ−ＴＬ６、ｐＥＣＥｄｈｆｒ−ＩＰ４７
５をそれぞれ３０μｇずつ用いてＳＰ２／０を形質転換
し、選択、活性測定、クロ−ニングを行うことにより融
合抗体発現細胞を樹立した。同様にして、ｐＸＰＣ−Ｔ
ＳＨ、ｐＸＰＥ−ＴＳＨ、ｐＣＨＩＰ１−ＴＨ８Ｅを用
いてＳＰ２／０を形質転換し、選択、活性測定、クロ−
ニングを行うことにより融合抗体発現細胞を樹立した。Similarly, pXPD-TSH, pSV2
-HCκneo-TL6, pECEdhfr-IP47
30 μg of each of 5 was used to transform SP2 / 0, and fusion antibody-expressing cells were established by performing selection, activity measurement, and cloning. Similarly, pXPC-T
SH2 / pXPE-TSH, pCHIP1-TH8E was used to transform SP2 / 0, and selection, activity measurement, and cloning were performed.
The fusion antibody-expressing cells were established by performing the cloning.

【００５４】実施例４．アルカリ・フォスファタ−ゼ融
合抗体の精製 実施例３により作製された細胞Ｈ１８Ａ・ＶＰ５ＩＰ−
３をＥ−ＲＤＦ（極東（株）製）−１％ＦＣＳ培地にて
増殖させた後、無血清のＥ−ＲＤＦ培地に約３×１０⁵
個／ｍｌの濃度で懸濁し、３日後遠心、フィルタ−濾過
により上清を回収した。上清９００ｍｌを限外濾過膜に
より約２０倍濃縮し、下記開始バッファ−にて透析後、
遠心上清を陰イオン交換カラムにより精製した。開始バ
ッファ−を１０ｍＭ Ｔｒｉｓ・ＨＣｌ（ｐＨ７）、溶
出バッファ−を１０ｍＭ Ｔｒｉｓ・ＨＣｌ−５００ｍ
Ｍ ＮａＣｌ（ｐＨ７）とし、５０ｍｌのＤＥＡＥ−Ｔ
ｏｙｏｐｅａｒｌ６５０Ｓ（東ソ−（株）製）を充填し
たカラムを５倍容量の開始バッファ−により平衡化し、
上記サンプルをアプライした。開始バッファ−から溶出
バッファ−へのそれぞれ５００ｍｌを用いた直線濃度勾
配により分画を行った。各画分を実施例３にある方法に
て活性測定を行い、アルカリ・フォスファタ−ゼ融合抗
体は、約０．１３Ｍ ＮａＣｌ付近に溶出することを確
認した。図１１に溶出パタ−ン、グラジエント、アルカ
リ・ファスファタ−ゼ活性について示す。Example 4. Purification of Alkaline-Phosphatase Fusion Antibody Cell H18A • VP5IP- Produced According to Example 3
3 was grown in E-RDF (Kyokuto Co., Ltd.)-1% FCS medium, and then added to serum-free E-RDF medium at about 3 × 10 ^5.
The cells were suspended at a concentration of 8 cells / ml, and after 3 days, the supernatant was recovered by centrifugation and filter-filtration. 900 ml of the supernatant was concentrated about 20 times with an ultrafiltration membrane, dialyzed with the following starting buffer,
The centrifugation supernatant was purified by an anion exchange column. Starting buffer is 10 mM Tris.HCl (pH 7), elution buffer is 10 mM Tris.HCl-500 m
M NaCl (pH 7), 50 ml DEAE-T
Equilibrate the column packed with oyopearl650S (manufactured by Toso Co., Ltd.) with 5 times the volume of the starting buffer,
The above sample was applied. Fractionation was performed by a linear concentration gradient using 500 ml each from the starting buffer to the elution buffer. The activity of each fraction was measured by the method described in Example 3, and it was confirmed that the alkaline phosphatase fusion antibody was eluted near about 0.13M NaCl. FIG. 11 shows the elution pattern, gradient, and alkaline phosphatase activity.

【００５５】さらに、開始バッファ−を５０ｍＭ Ｔｒ
ｉｓ・ＨＣｌ−１Ｍ 硫酸アンモニウム（ｐＨ７）、溶
出バッファ−を５０ｍＭ Ｔｒｉｓ・ＨＣｌ（ｐＨ７）
とし、Ｐｈｅｎｙｌ−５ＰＷ（東ソ−（株）製）を用い
て、開始バッファ−から溶出バッファ−へ１００ｍｌで
の直線濃度勾配により分画を行った。ＤＥＡＥ−Ｔｏｙ
ｏｐｅａｒｌ６５０Ｓからの画分８．５ｍｌに１．５ｇ
の硫酸アンモニウムを加え、上記精製を行ったところ、
アルカリフォスファタ−ゼは０．６Ｍ、アルカリ・フォ
スファタ−ゼ融合抗体は０．５Ｍ硫酸アンモニウム付近
に溶出した。Furthermore, the starting buffer was set to 50 mM Tr.
is · HCl-1M ammonium sulfate (pH 7), elution buffer is 50 mM Tris · HCl (pH 7)
Then, using Phenyl-5PW (manufactured by Toso Co., Ltd.), fractionation was performed from the starting buffer to the elution buffer by a linear concentration gradient of 100 ml. DEAE-Toy
Fraction from opearl 650S 1.5 g in 8.5 ml
Ammonium sulphate was added and the above purification was performed,
Alkaline phosphatase was eluted at 0.6M, and alkaline phosphatase fusion antibody was eluted near 0.5M ammonium sulfate.

【００５６】実施例５．アルカリ・フォスファタ−ゼ融
合抗体の抗原認識能の確認 実施例４に記載の融合抗体の抗原であるフコシルＳＳＥ
Ａ−１を固相化したＥＬＩＳＡ用プレ−トは特開平６−
１５３９５５号に記載の方法により作製した。実施例４
により作成した精製サンプルを適当な濃度に希釈して用
い、実験対照区としてはキメラＨ１８Ａ抗体を用いた。
これらのサンプルを各ウエル１００μｌずつ分注し２時
間放置後、ＰＢＳにて洗浄した。キメラＨ１８Ａ抗体に
対しては、検出用抗体であるホ−スラディッシュ・ペル
オキシダ−ゼ（ＨＲＰ）が結合されている坑ヒトＩｇκ
を加え２時間放置後洗浄した。アルカリ・フォスファタ
−ゼ、ＨＲＰ用基質を添加、発色の後、それぞれ４０
５、４１５ｎｍの吸光度を測定した。結果を図１２に示
す。図１２で明らかなように、アルカリ・フォスファタ
−ゼ融合抗体は本来の抗原認識能を保持し、アルカリ・
フォスファタ−ゼ活性を保持していた。Example 5. Confirmation of Antigen Recognition Ability of Alkaline-Phosphatase Fusion Antibody Fucosyl SSE which is the antigen of the fusion antibody described in Example 4
A plate for ELISA in which A-1 is immobilized is disclosed in JP-A-6-
It was prepared by the method described in No. 153955. Example 4
The purified sample prepared in 1 above was diluted to an appropriate concentration and used, and a chimeric H18A antibody was used as an experimental control.
100 μl of each sample was dispensed into each well, left for 2 hours, and then washed with PBS. For the chimeric H18A antibody, an anti-human Igκ to which a detection antibody, horseradish peroxidase (HRP), is bound.
Was added, and the mixture was left for 2 hours and washed. After adding alkaline phosphatase and HRP substrate and developing color, 40
The absorbance at 5,415 nm was measured. Results are shown in FIG. As is clear from FIG. 12, the alkaline phosphatase fusion antibody retains the original antigen recognition ability and
It retained phosphatase activity.

【００５７】[0057]

【発明の効果】本発明によれば、均一な性質を有する組
換えＡＰ融合抗体又は組換えＡＰ融合タンパク質を製造
するための発現ベクタ−や、それを用いた前記融合抗体
又はタンパク質の製造方法等が提供される。INDUSTRIAL APPLICABILITY According to the present invention, an expression vector for producing a recombinant AP fusion antibody or recombinant AP fusion protein having a uniform property, a method for producing the fusion antibody or protein using the expression vector, etc. Will be provided.

【００５８】本発明では、発現ベクタ−中に融合抗体や
融合タンパク質と融合タンパク質を発現する様、これら
抗体等をコ−ドする遺伝子と融合配置されたＡＰ遺伝
子、及び、遊離ＡＰ分子を発現する様、これら抗体等を
コ−ドする遺伝子とは独立して配置されたＡＰ遺伝子
の、２種のＡＰ遺伝子を使用する。これにより、抗体等
と強固にペプチド結合したＡＰ分子と遊離のＡＰ分子を
発現させ、後にこれらを二量体化させることで、従来の
ＡＰ融合抗体等と比較して、極めてＡＰ活性の高い組換
えＡＰ融合抗体等を得ることができる。In the present invention, an AP gene fused with a gene encoding these antibodies or the like and a free AP molecule are expressed so that the fusion antibody or the fusion protein and the fusion protein are expressed in the expression vector. Similarly, two kinds of AP genes, which are AP genes arranged independently of genes encoding these antibodies and the like, are used. As a result, by expressing an AP molecule strongly peptide-bonded to an antibody and the like and a free AP molecule and dimerizing these later, a group having an extremely high AP activity as compared with a conventional AP fusion antibody and the like. A modified AP fusion antibody or the like can be obtained.

【００５９】本発明により得られる組換えＡＰ融合タン
パク質等は、その均一性、高活性等から、特に高感度化
及び高精度化が必要なサンドイッチ又は競合免疫測定に
使用する標識抗体又は標識抗原として好適である。The recombinant AP fusion protein or the like obtained by the present invention is used as a labeled antibody or a labeled antigen for sandwich or competitive immunoassay, which requires particularly high sensitivity and precision because of its homogeneity and high activity. It is suitable.

【図面の簡単な説明】[Brief description of drawings]

【図１】図１はプラスミドｐＨＣＧ１のおもな制限酵素
部位のおよその位置と、遺伝子の各部分の構成を示すも
のである。FIG. 1 shows the approximate positions of major restriction enzyme sites of plasmid pHCG1 and the constitution of each part of the gene.

【図２】図２はプラスミドｐＶＰ５のおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 2 shows the approximate positions of major restriction enzyme sites of plasmid pVP5 and the constitution of each part of the gene.

【図３】図３はプラスミドｐＶＰ３のおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 3 shows the approximate positions of major restriction enzyme sites of plasmid pVP3 and the constitution of each part of the gene.

【図４】図４はプラスミドｐＺＰ１のおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 4 shows the approximate positions of major restriction enzyme sites of plasmid pZP1 and the constitution of each part of the gene.

【図５】図５はプラスミドｐＺＰ２のおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 5 shows the approximate positions of major restriction enzyme sites of plasmid pZP2 and the constitution of each part of the gene.

【図６】図６はプラスミドｐＸＰＣのおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 6 shows the approximate positions of major restriction enzyme sites of plasmid pXPC and the constitution of each part of the gene.

【図７】図７はプラスミドｐＸＰＤのおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 7 shows the approximate positions of major restriction enzyme sites of the plasmid pXPD and the constitution of each part of the gene.

【図８】図８はプラスミドｐＸＰＥのおもな制限酵素部
位のおよその位置と、遺伝子の各部分の構成を示すもの
である。FIG. 8 shows the approximate positions of major restriction enzyme sites of plasmid pXPE and the constitution of each part of the gene.

【図９】図９はプラスミドｐＣＨＩＰ１のおもな制限酵
素部位のおよその位置と、遺伝子の各部分の構成を示す
ものである。FIG. 9 shows the approximate positions of major restriction enzyme sites of plasmid pCHIP1 and the constitution of each part of the gene.

【図１０】図１０はプラスミドｐＶＰ３−Ｈ１８Ａのお
もな制限酵素部位のおよその位置と、遺伝子の各部分の
構成を示すものである。FIG. 10 shows the approximate positions of major restriction enzyme sites of plasmid pVP3-H18A and the constitution of each part of the gene.

【図１１】図１１はＨ１８Ａ・ＶＰ５ＩＰ−３の培養上
清のＤＥＡＥ−Ｔｏｙｏｐｅａｒｌでの精製の状況を示
す。実線は２８０ｎｍにおける吸光度を、点線はＮａＣ
ｌのグラジエントを、黒丸は実施例３に記した測定法に
基づき、抗ヒトＦ（ａｂ´）₂抗体に結合するアルカリ
フォスファタ−ゼの活性を測定したものである。FIG. 11 shows the state of purification of culture supernatant of H18A · VP5IP-3 with DEAE-Toyopearl. The solid line is the absorbance at 280 nm and the dotted line is NaC.
Based on the measurement method described in Example 3, the gradient of 1 is based on the measurement method described in Example 3, and the activity of alkaline phosphatase bound to the anti-human F (ab ′) ₂ antibody is measured.

【図１２】図１２は、融合抗体の抗原認識能を調べたも
のである。横軸方向は、プレ−トに固定する抗原の希釈
度を示し、縦軸はそれぞれの活性を吸光度で示したもの
である。図中白丸を実線で結んだものは、アルカリフォ
スファタ−ゼを融合させた抗体であり、四角を点線で結
んだものは、実験対照のキメラ抗体である。FIG. 12 shows the examination of the antigen recognition ability of the fusion antibody. The horizontal axis represents the dilution of the antigen immobilized on the plate, and the vertical axis represents the respective activities in terms of absorbance. In the figure, the white circles connected by a solid line are the antibodies fused with alkaline phosphatase, and the squares connected by the dotted lines are the experimental control chimeric antibodies.

【配列表】配列番号：１ 配列の長さ：１５８７ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 ATG CAG GGG CCC TGG GTG CTG CTG CTG CTG GGC CTG AGG CTA CAG 45 Met Gln Gly Pro Trp Val Leu Leu Leu Leu Gly Leu Arg Leu Gln CTC TCC CTG GGC GTC ATC CCA GCT GAG GAG GAG AAC CCG GCC TTC 90 Leu Ser Leu Gly Val Ile Pro Ala Glu Glu Glu Asn Pro Ala Phe TGG AAC CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC AAG AAG CTG 135 Trp Asn Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala Lys Lys Leu CAG CCC ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC 180 Gln Pro Ile Gln Lys Val Ala Lys Asn Leu Ile Leu Phe Leu Gly GAT GGG TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG 225 Asp Gly Leu Gly Val Pro Thr Val Thr Ala Thr Arg Ile Leu Lys GGG CAG AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG 270 Gly Gln Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro Leu Ala Met GAC CGC TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC 315 Asp Arg Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp AGA CAG GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC 360 Arg Gln Val Pro Asp Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys GGG GTC AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC 405 Gly Val Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala CGC TTT AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC 450 Arg Phe Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu Val Ile Ser GTG ATG AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG 495 Val Met Asn Arg Ala Lys Gln Ala Gly Lys Ser Val Gly Val Val ACC ACC ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA 540 Thr Thr Thr Arg Val Gln His Ala Ser Pro Ala Gly Thr Tyr Ala CAC ACA GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC 585 His Thr Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala TCA GCC CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC 630 Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile TCC AAC ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC 675 Ser Asn Met Asp Ile Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr ATG TTT CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC 720 Met Phe Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala AGC CAG AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA 765 Ser Gln Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu Val Gln Glu TGG CTG GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT 810 Trp Leu Ala Lys His Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr GAG CTC ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG 855 Glu Leu Met Gln Ala Ser Leu Asp Gln Ser Val Thr His Leu Met GGC CTC TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC 900 Gly Leu Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp CCC ACA CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG 945 Pro Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu CGC CTG CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG 990 Arg Leu Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu GGC GGC CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG 1035 Gly Gly Arg Ile Asp His Gly His His Glu Gly Val Ala Tyr Gln GCA GTC ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG 1080 Ala Val Thr Glu Ala Val Met Phe Asp Asp Ala Ile Glu Arg Ala GGC CAG CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT 1125 Gly Gln Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu Val Thr Ala GAC CAC TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG 1170 Asp His Ser His Val Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly AGC TCC ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA 1215 Ser Ser Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys GCC TAC ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC 1260 Ala Tyr Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe AAC TCA GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC 1305 Asn Ser Gly Val Arg Pro Asp Val Asn Glu Ser Glu Ser Gly Ser CCC GAT TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC 1350 Pro Asp Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser Ser Glu Thr CAC GGA GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG 1395 His Gly Gly Glu Asp Val Ala Val Phe Ala Arg Gly Pro Gln Ala CAC CTG GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC 1440 His Leu Val His Gly Val Gln Glu Gln Ser Phe Val Ala His Val ATG GCC TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC TGC GAC CTG 1485 Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys Asp Leu GCG CTC CCC GCC TGC ACC ACC GAC GCC GCG CAC CCA GTT GCC GCG 1530 Ala Leu Pro Ala Cys Thr Thr Asp Ala Ala His Pro Val Ala Ala TCG CTG CCA CTG CTG GCC GGG ACC CTG CTG CTG CTG GGG GCG TCC 1575 Ser Leu Pro Leu Leu Ala Gly Thr Leu Leu Leu Leu Gly Ala Ser GCT GCT CCC TGA 1587 Ala Ala Pro *** 配列番号：２ 配列の長さ：２００９ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG 241 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu GCA CCC TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC 286 Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly TGC CTG GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG 331 Cys Leu Val Lys AspTyr Phe Pro Glu Pro Val Thr Val Ser Trp AAC TCA GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC 376 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val CTA CAG TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG 421 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val CCC TCC AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT 466 Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn CAC AAG CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC 562 TGGACGCATC CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA ACCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp Lys ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC CCC CCA AAA 1101 Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys CCC AAG GAC ACC CTC ATG ATC TCC CGG ACC CCT GAG GTC ACA TGC 1146 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys GTG GTG GTG GAC GTG AGC CAC GAA GAC CCT GAG GTC AAG TTC AAC 1191 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn TGG TAC GTG GAC GGC GTG GAG GTG CAT AAT GCC AAG ACA AAG CCG 1236 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro CGG GAG GAG CAG TAC AAC AGC ACG TAC CGG GTG GTC AGC GTC CTC 1281 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu ACC GTC CTG CAC CAG GAC TGG CTG AAT GGC AAG GAG TAC AAG TGC 1326 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys AAG GTC TCC AAC AAA GCC CTC CCA GCC CCC ATC GAG AAA ACC ATC 1371 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile TCC AAA GCC AAA GGTGGGACCC GTGGGGTGCG AGGGCCACAT GGACAGAGGC 1423 Ser Lys Ala Lys CGGCTCGGCC CACCCTCTGC CCTGAGAGTG ACCGCTGTAC CAACCTCTGT 1473 CCTACA GGG CAG CCC CGA GAA CCA CAG GTG TAC ACC CTG CCC CCA 1518 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro TCC CGG GAT GAG CTG ACC AAG AAC CAG GTC AGC CTG ACC TGC CTG 1563 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu GTC AAA GGC TTC TAT CCC AGC GAC ATC GCC GTG GAG TGG GAG AGC 1608 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AAT GGG CAG CCG GAG AAC AAC TAC AAG ACC ACG CCT CCC GTG CTG 1653 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu GAC TCC GAC GGC TCC TTC TTC CTC TAC AGC AAG CTC ACC GTG GAC 1698 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp AAG AGC AGG TGG CAG CAG GGG AAC GTC TTC TCA TGC TCC GTG ATG 1743 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met CAT GAG GCT CTG CAC AAC CAC TAC ACG CAG AAG AGC CTC TCC CTG 1788 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu TCT CCG GGT AAA TGA GTGCGACGGC CGGCAAGCCC CGCTCCCCGG 1833 Ser Pro Gly Lys *** GCTCTCGCGG TCGCACGAGG ATGCTTGGCA CGTACCCCCT GTACATACTT 1883 CCCGGGCGCC CAGCATGGAA ATAAAGCACC CAGCGCTGCC CTGGGCCCCT 1933 GCGAGACTGT GATGGTTCTT TCCACGGGTC AGGCCGAGTC TGAGGCCTGA 1983 GTGGCATGAG GGAGGCAGAG CGGGTC 2009 配列番号：３ 配列の長さ：２４８４ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCA GCC TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA CCC 247 ??? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC TGGACGCATC 572 CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCTAACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGC AGA GCC CAA ATC TTG TGA CAA AAC TCA CAC 919 Glu Pro Lys Ser Cys Asp Lys Thr His Thr ATG CCC ACC GTG CCC AGGTAAGCCA GCCCAGGCCT CGCCCTCCAG 964 Cys Pro Pro Cys Pro CTCAAGGCGG GACAGGTGCC CTAGAGTAGC CTGCATCCAG GGACAGGCCC 1014 CAGCCGGGTG CTGACACGTC CACCTCCATC TCTTCCTCA GCA CCT GCT AGT 1065 Ala Pro Ala Ser CCT GAG GAG GAG AAC CCG GCC TTC TGG AAC CGC CAG GCA GCT GAG 1110 Pro Glu Glu Glu Asn Pro Ala Phe Trp Asn Arg Gln Ala Ala Glu GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC 1155 Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG 1200 Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG 1245 Val Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT 1290 Gly Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA 1335 Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG 1380 Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG 1425 Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA 1470 Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC 1515 Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG 1560 Ala Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC 1605 Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG 1650 Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA 1695 Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG 1740 Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT 1785 Asp Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG 1830 Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC 1875 Asp Gln Ser Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG 1920 Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC 1965 Met Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT 2010 Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG 2055 His His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG 2100 Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC 2145 Asp Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC 2190 Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC 2235 Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC 2280 Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG 2325 Val Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG 2370 Ala Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG 2415 Val Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG 2460 Glu Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu GAG CCC TAC ACG GCC TGC CTC TAG 2484 Glu Pro Tyr Thr Ala Cys Leu *** 配列番号：４ 配列の長さ：２４６０ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCA GCC TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA CCC 247 ??? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC TGGACGCATC 572 CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCTAACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA ACT CAC ACA 919 Glu Pro Lys Ser Cys Asp Lys Thr His Thr TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC GCCCTCCAGC 965 Cys Pro Pro Cys Pro TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG GACAGGCCCC 1015 AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA CCT GCT AGT 1065 Ala Pro Ala Ser CCT GAG GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG 1110 Pro Glu Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG 1155 Val Ala Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC 1200 Pro Thr Val Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC 1245 Lys Leu Gly Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC 1290 Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC 1335 Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC 1380 Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC 1425 Asn Thr Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG 1470 Lys Gln Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC 1515 Gln His Ala Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG 1560 Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT 1605 Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG 1650 Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC 1695 Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC 1740 Arg Leu Asp Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG 1785 Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC 1830 Ser Leu Asp Gln Ser Val Thr His Leu Met Gly Leu Phe Glu Pro GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC 1875 Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG 1920 Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC 1965 Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG 2010 His Gly His His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC 2055 Val Met Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC 2100 Glu Glu Asp Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG 2145 Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC 2190 Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA 2235 Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG 2280 Pro Asp Val Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC 2325 Gln Ala Ala Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT 2370 Val Ala Val Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC 2415 Val Gln Glu Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala TGT CTG GAG CCC TAC ACG GCC TGC CTC TAG 2445 Cys Leu Glu Pro Tyr Thr Ala Cys Leu *** 配列番号：５ 配列の長さ：３１０８ 配列の型：核酸 配列の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA 244 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala CCC TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC 289 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys CTG GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC 334 Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn TCA GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA 379 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu CAG TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC 424 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro TCC AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC 469 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His AAG CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC 562 TGGACGCATC CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp Lys ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC CCC CCA AAA 1101 Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys CCC AAG GAC ACC CTC ATG ATC TCC CGG ACC CCT GAG GTC ACA TGC 1146 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys GTG GTG GTG GAC GTG AGC CAC GAA GAC CCT GAG GTC AAG TTC AAC 1191 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn TGG TAC GTG GAC GGC GTG GAG GTG CAT AAT GCC AAG ACA AAG CCG 1236 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro CGG GAG GAG CAG TAC AAC AGC ACG TAC CGG GTG GTC AGC GTC CTC 1281 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu ACC GTC CTG CAC CAG GAC TGG CTG AAT GGC AAG GAG TAC AAG TGC 1326 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys AAG GTC TCC AAC AAA GCC CTC CCA GCC CCC ATC GAG AAA ACC ATC 1371 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile TCC AAA GCC AAA GGTGGGACCC GTGGGGTGCG AGGGCCACAT GGACAGAGGC 1423 Ser Lys Ala Lys CGGCTCGGCC CACCCTCTGC CCTGAGAGTG ACCGCTGTAC CAACCTCTGT 1473 CCTACA GGG CAG CCC CGA GAA CCA CAG GTG TAC ACC CTG CCC CCA 1518 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro TCC CGG GAT GAG CTG ACC AAG AAC CAG GTC AGC CTG ACC TGC CTG 1563 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu GTC AAA GGC TTC TAT CCC AGC GAC ATC GCC GTG GAG TGG GAG AGC 1608 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AAT GGG CAG CCG GAG AAC AAC TAC AAG ACC ACG CCT CCC GTG CTG 1653 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu GAC TCC GAC GGC TCC TTC TTC CTC TAC AGC AAG CTC ACC GTG GAC 1698 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp AAG AGC AGG TGG CAG CAG GGG AAC GCT AGT CCT GAG GCC CTG GAT 1743 Lys Ser Arg Trp Gln Gln Gly Asn Ala Ser Pro Glu Ala Leu Asp GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC AAG AAC CTC 1788 Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala Lys Asn Leu ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG GTG ACA GCC 1833 Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr Val Thr Ala ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG GGG CCT GAG 1878 Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu Gly Pro Glu ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT CTG TCC AAG 1923 Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala Leu Ser Lys ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA GCC ACA GCC 1968 Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala Ala Thr Ala ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG ACC ATC GGC 2013 Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln Thr Ile Gly TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG ACA CGC GGC 2058 Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr Thr Arg Gly AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA GCA GGA AAG 2103 Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln Ala Gly Lys TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC GCC TCG CCA 2148 Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His Ala Ser Pro GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG TAC TCA GAT 2193 Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr Ser Asp GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC CAG GAC ATC 2238 Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG ATC CTT GGC 2283 Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile Leu Gly GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA GAC CCT GAG 2328 Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro Asp Pro Glu TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG GAC GGG AAG 2373 Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu Asp Gly Lys AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT GCC TGG TAT 2418 Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly Ala Trp Tyr GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG GAC CAG TCT 2463 Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu Asp Gln Ser GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC ACG AAA TAT 2508 Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp Thr Lys Tyr GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG ATG GAG ATG 2553 Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu Met Glu Met ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC CGC GGC TTC 2598 Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro Arg Gly Phe TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT CAT CAT GAG 2643 Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly His His Glu GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG TTC GAC GAC 2688 Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met Phe Asp Asp GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG GAC ACG CTG 2733 Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu Asp Thr Leu ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC TTT GGT GGC 2778 Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser Phe Gly Gly TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC CCC AGC AAG 2823 Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala Pro Ser Lys GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC GGC AAT GGC 2868 Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr Gly Asn Gly CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC GTG AAT GAG 2913 Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp Val Asn Glu AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG GCG GTG CCC 2958 Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala Ala Val Pro CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG GTG TTT GCG 3003 Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ala CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG GAG CAG AGC 3048 Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln Glu Gln Ser TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG GAG CCC TAC 3093 Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr ACG GCC TGC CTC TAG 3108 Thr Ala Cys Leu *** 配列番号：６ 配列の長さ：３１４７ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA 244 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala CCC TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC 289 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys CTG GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC 334 Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn TCA GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA 379 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu CAG TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC 424 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro TCC AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC 469 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His AAG CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC 562 TGGACGCATC CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp LyS ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC CCC CCA AAA 1101 Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys CCC AAG GAC ACC CTC ATG ATC TCC CGG ACC CCT GAG GTC ACA TGC 1146 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys GTG GTG GTG GAC GTG AGC CAC GAA GAC CCT GAG GTC AAG TTC AAC 1191 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn TGG TAC GTG GAC GGC GTG GAG GTG CAT AAT GCC AAG ACA AAG CCG 1236 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro CGG GAG GAG CAG TAC AAC AGC ACG TAC CGG GTG GTC AGC GTC CTC 1281 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu ACC GTC CTG CAC CAG GAC TGG CTG AAT GGC AAG GAG TAC AAG TGC 1326 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys AAG GTC TCC AAC AAA GCC CTC CCA GCC CCC ATC GAG AAA ACC ATC 1371 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile TCC AAA GCC AAA GGTGGGACCC GTGGGGTGCG AGGGCCACAT GGACAGAGGC 1423 Ser Lys Ala Lys CGGCTCGGCC CACCCTCTGC CCTGAGAGTG ACCGCTGTAC CAACCTCTGT 1473 CCTACA GGG CAG CCC CGA GAA CCA CAG GTG TAC ACC CTG CCC CCA 1518 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro TCC CGG GAT GAG CTG ACC AAG AAC CAG GTC AGC CTG ACC TGC CTG 1563 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu GTC AAA GGC TTC TAT CCC AGC GAC ATC GCC GTG GAG TGG GAG AGC 1608 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AAT GGG CAG CCG GAG AAC AAC TAC AAG ACC ACG CCT CCC GTG CTG 1653 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu GAC TCC GAC GGC TCC TTC TTC CTC TAC AGC AAG CTC ACC GTG GAC 1698 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp AAG AGC AGG TGG CAG CAG GGG AAC GCT AGT CCT GAG GAG GAG AAC 1743 Lys Ser Arg Trp Gln Gln Gly Asn Ala Ser Pro Glu Glu Glu Asn CCG GCC TTC TGG AAC CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC 1788 Pro Ala Phe Trp Asn Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC 1833 Lys Lys Leu Gln Pro Ile Gln Lys Val Ala Lys Asn Leu Ile Leu TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG 1878 Phe Leu Gly Asp Gly Leu Gly Val Pro Thr Val Thr Ala Thr Arg ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC 1923 Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC 1968 Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC 2013 Asn Val Asp Arg Gln Val Pro Asp Ser Ala Ala Thr Ala Thr Ala TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT 2058 Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG 2103 Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA 2148 Val Ile Ser Val Met Asn Arg Ala Lys Gln Ala Gly Lys Ser Val GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC 2193 Gly Val Val Thr Thr Thr Arg Val Gln His Ala Ser Pro Ala Gly ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC 2238 Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT 2283 Met Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC 2328 Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile Leu Gly Gly Gly CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA 2373 Arg Lys Tyr Met Phe Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG 2418 Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG 2463 Val Gln Glu Trp Leu Ala Lys His Gln Gly Ala Trp Tyr Val Trp AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC 2508 Asn Arg Thr Glu Leu Met Gln Ala Ser Leu Asp Gln Ser Val Thr CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC 2553 His Leu Met Gly Leu Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG 2598 Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC 2643 Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG 2688 Phe Val Glu Gly Gly Arg Ile Asp His Gly His His Glu Gly Val GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT 2733 Ala Tyr Gln Ala Val Thr Glu Ala Val Met Phe Asp Asp Ala Ile GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC 2778 Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC 2823 Val Thr Ala Asp His Ser His Val Phe Ser Phe Gly Gly Tyr Thr TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG 2868 Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC 2913 Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG 2958 Tyr Val Phe Asn Ser Gly Val Arg Pro Asp Val Asn Glu Ser Glu AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG 3003 Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC 3048 Ser Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ala Arg Gly CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA 3093 Pro Gln Ala His Leu Val His Gly Val Gln Glu Gln Ser Phe Val GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC 3138 Ala His Val Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala TGC CTC TAG 3147 Cys Leu *** 配列番号：７ 配列の長さ：３０２２ 配列の型：ＤＮＡ 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA CCC 247 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC TGGACGCATC 572 CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCTAACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA ACT CAC ACA 920 Glu Pro Lys Ser Cys Asp Lys Thr His Thr TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC GCCCTCCAGC 965 Cys Pro Pro Cys Pro TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG GACAGGCCCC 1015 AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA CCT GCT AGT 1065 Ala Pro Ala Ser CCT GAG GAG GAG AAC CCG GCC TTC TGG AAC CGC CAG GCA GCT GAG 1110 Pro Glu Glu Glu Asn Pro Ala Phe Trp Asn Arg Gln Ala Ala Glu GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC 1155 Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG 1200 Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG 1245 Val Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT 1290 Gly Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA 1335 Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG 1380 Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG 1425 Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA 1470 Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC 1515 Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG 1560 Ala Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC 1605 Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG 1650 Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA 1695 Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG 1740 Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT 1785 Asp Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG 1830 Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC 1875 Asp Gl nSer Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG 1920 Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC 1965 Met Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT 2010 Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG 2055 His His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG 2100 Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC 2145 Asp Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC 2190 Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC 2235 Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC 2280 Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG 2325 Val Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG 2370 Ala Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG 2415 Val Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG 2460 Glu Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu GAG CCC TAC ACG GCC TGC CTC TAG ATCTCTATAA TCTCGCGCAA 2504 Glu Pro Tyr Thr Ala Cys Leu *** CCTATTTTCC CCTCGAGAAC ACTTTTTAAG CCGTAGATAA ACAGGCTGGG 2554 ACACTTCAC ATG AGC GAA AAA TAC ATC GTC ACC TGG GAC ATG TTG 2599 Met Ser Glu Lys Tyr Ile Val Thr Trp Asp Met Leu CAG ATC CAT GCA CGT AAA CTC GCA AGC CGA CTG ATG CCT TCT GAA 2644 Gln Ile His Ala Arg Lys Leu Ala Ser Arg Leu Met Pro Ser Glu CAA TGG AAA GGC ATT ATT GCC GTA AGC CGT GGC GGT CTG GTA CCG 2689 Gln Trp Lys Gly Ile Ile Ala Val Ser Arg Gly Gly Leu Val Pro GGT GCG TTA CTG GCG CGT GAA CTG GGT ATT CGT CAT GTC GAT ACC 2734 Gly Ala Leu Leu Ala Arg Glu Leu Gly Ile Arg His Val Asp Thr GTT TGT ATT TCC AGC TAC GAT CAC GAC AAC CAG CGC GAG CTT AAA 2779 Val Cys Ile Ser Ser Tyr Asp His Asp Asn Gln Arg Glu Leu Lys GTG CTG AAA CGC GCA GAA GGC GAT GGC GAA GGC TTC ATC GTT ATT 2824 Val Leu Lys Arg Ala Glu Gly Asp Gly Glu Gly Phe Ile Val Ile GAT GAC CTG GTG GAT ACC GGT GGT ACT GCG GTT GCG ATT CGT GAA 2869 Asp Asp Leu Val Asp Thr Gly Gly Thr Ala Val Ala Ile Arg Glu ATG TAT CCA AAA GCG CAC TTT GTC ACC ATC TTC GCA AAA CCG GCT 2914 Met Tyr Pro Lys Ala His Phe Val Thr Ile Phe Ala Lys Pro Ala GGT CGT CCG CTG GTT GAT GAC TAT GTT GTT GAT ATC CCG CAA GAT 2959 Gly Arg Pro Leu Val Asp Asp Tyr Val Val Asp Ile Pro Gln Asp ACC TGG ATT GAA CAG CCG TGG GAT ATG GGC GTC GTA TTC GTC CCG 3004 Thr Trp Ile Glu Gln Pro Trp Asp Met Gly Val Val Phe Val Pro CCA ATC TCC GGT CGC TAA 3022 Pro Ile Ser Gly Arg *** 配列番号：８ 配列の長さ：３０７６ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA CCC 247 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC 562 TGGACGCATC CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp Lys ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC CCC CCA AAA 1101 Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys CCC AAG GAC GTC ATC CCA GCT GAG GAG GAG AAC CCG GCC TTC TGG 1146 Pro Lys Asp Val Ile Pro Ala Glu Glu Glu Asn Pro Ala Phe Trp AAC CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC AAG AAG CTG CAG 1191 Asn Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala Lys Lys Leu Gln CCC ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC GAT 1236 Pro Ile Gln Lys Val Ala Lys Asn Leu Ile Leu Phe Leu Gly Asp GGG TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG GGG 1281 Gly Leu Gly Val Pro Thr Val Thr Ala Thr Arg Ile Leu Lys Gly CAG AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG GAC 1326 Gln Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro Leu Ala Met Asp CGC TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC AGA 1371 Arg Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp Arg CAG GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC GGG 1416 Gln Val Pro Asp Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys Gly GTC AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC CGC 1461 Val Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg TTT AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC GTG 1506 Phe Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu Val Ile Ser Val ATG AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG ACC 1551 Met Asn Arg Ala Lys Gln Ala Gly Lys Ser Val Gly Val Val Thr ACC ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA CAC 1596 Thr Thr Arg Val Gln His Ala Ser Pro Ala Gly Thr Tyr Ala His ACA GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC TCA 1641 Thr Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala Ser GCC CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC TCC 1686 Ala Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile Ser AAC ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC ATG 1731 Asn Met Asp Ile Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr Met TTT CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC AGC 1776 Phe Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala Ser CAG AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA TGG 1821 Gln Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu Val Gln Glu Trp CTG GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT GAG 1866 Leu Ala Lys His Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr Glu CTC ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG GGC 1911 Leu Met Gln Ala Ser Leu Asp Gln Ser Val Thr His Leu Met Gly CTC TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC CCC 1956 Leu Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp Pro ACA CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG CGC 2001 Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg CTG CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG GGC 2046 Leu Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu Gly GGC CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG GCA 2091 Gly Arg Ile Asp His Gly His His Glu Gly Val Ala Tyr Gln Ala GTC ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG GGC 2136 Val Thr Glu Ala Val Met Phe Asp Asp Ala Ile Glu Arg Ala Gly CAG CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT GAC 2181 Gln Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu Val Thr Ala Asp CAC TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG AGC 2226 His Ser His Val Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly Ser TCC ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA GCC 2271 Ser Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys Ala TAC ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC AAC 2316 Tyr Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe Asn TCA GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC CCC 2361 Ser Gly Val Arg Pro Asp Val Asn Glu Ser Glu Ser Gly Ser Pro GAT TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC CAC 2406 Asp Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser Ser Glu Thr His GGA GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG CAC 2451 Gly Gly Glu Asp Val Ala Val Phe Ala Arg Gly Pro Gln Ala His CTG GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC ATG 2496 Leu Val His Gly Val Gln Glu Gln Ser Phe Val Ala His Val Met GCC TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC TGC CTC TAG 2538 Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys Leu *** ATCTCTATAA TCTCGCGCAA CCTATTTTCC CCTCGAGAAC ACTTTTTAAG 2588 CCGTAGATAA ACAGGCTGGG ACACTTCAC ATG AGC GAA AAA TAC ATC GTC 2638 Met Ser Glu Lys Tyr Ile Val ACC TGG GAC ATG TTG CAG ATC CAT GCA CGT AAA CTC GCA AGC CGA 2683 Thr Trp Asp Met Leu Gln Ile His Ala Arg Lys Leu Ala Ser Arg CTG ATG CCT TCT GAA CAA TGG AAA GGC ATT ATT GCC GTA AGC CGT 2728 Leu Met Pro Ser Glu Gln Trp Lys Gly Ile Ile Ala Val Ser Arg GGC GGT CTG GTA CCG GGT GCG TTA CTG GCG CGT GAA CTG GGT ATT 2773 Gly Gly Leu Val Pro Gly Ala Leu Leu Ala Arg Glu Leu Gly Ile CGT CAT GTC GAT ACC GTT TGT ATT TCC AGC TAC GAT CAC GAC AAC 2818 Arg His Val Asp Thr Val Cys Ile Ser Ser Tyr Asp His Asp Asn CAG CGC GAG CTT AAA GTG CTG AAA CGC GCA GAA GGC GAT GGC GAA 2863 Gln Arg Glu Leu Lys Val Leu Lys Arg Ala Glu Gly Asp Gly Glu GGC TTC ATC GTT ATT GAT GAC CTG GTG GAT ACC GGT GGT ACT GCG 2908 Gly Phe Ile Val Ile Asp Asp Leu Val Asp Thr Gly Gly Thr Ala GTT GCG ATT CGT GAA ATG TAT CCA AAA GCG CAC TTT GTC ACC ATC 2953 Val Ala Ile Arg Glu Met Tyr Pro Lys Ala His Phe Val Thr Ile TTC GCA AAA CCG GCT GGT CGT CCG CTG GTT GAT GAC TAT GTT GTT 2998 Phe Ala Lys Pro Ala Gly Arg Pro Leu Val Asp Asp Tyr Val Val GAT ATC CCG CAA GAT ACC TGG ATT GAA CAG CCG TGG GAT ATG GGC 3043 Asp Ile Pro Gln Asp Thr Trp Ile Glu Gln Pro Trp Asp Met Gly GTC GTA TTC GTC CCG CCA ATC TCC GGT CGC TAA 3076 Val Val Phe Val Pro Pro Ile Ser Gly Arg *** 配列番号：９ 配列の長さ：３１２７ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA CCC 247 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC TGGACGCATC 572 CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCTAACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA ACT CAC ACA 920 Glu Pro Lys Ser Cys Asp Lys Thr His Thr TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC GCCCTCCAGC 965 Cys Pro Pro Cys Pro TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG GACAGGCCCC 1015 AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA CCT GAA CTC 1065 Ala Pro Glu Leu CTG GGG GGA CCG TCA GTC TTC CTC TTC CCC CCA AAA CCC AAG GAC 1110 Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp GTC GGT GGC GGC GGT TCA GGC GGT GGT GGA TCT GGT GGT GGC GGG 1155 Val Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly TCA GAC GTC ATC CCA GCT GAG GAG GAG AAC CCG GCC TTC TGG AAC 1200 Ser Asp Val Ile Pro Ala Glu Glu Glu Asn Pro Ala Phe Trp Asn CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC 1245 Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG 1290 Ile Gln Lys Val Ala Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG 1335 Leu Gly Val Pro Thr Val Thr Ala Thr Arg Ile Leu Lys Gly Gln AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC 1380 Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro Leu Ala Met Asp Arg TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG 1425 Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC 1470 Val Pro Asp Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT 1515 Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG 1560 Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu Val Ile Ser Val Met AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC 1605 Asn Arg Ala Lys Gln Ala Gly Lys Ser Val Gly Val Val Thr Thr ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA 1650 Thr Arg Val Gln His Ala Ser Pro Ala Gly Thr Tyr Ala His Thr GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC 1695 Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC 1740 Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT 1785 Met Asp Ile Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG 1830 Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG 1875 Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu Val Gln Glu Trp Leu GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC 1920 Ala Lys His Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC 1965 Met Gln Ala Ser Leu Asp Gln Ser Val Thr His Leu Met Gly Leu TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA 2010 Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG 2055 Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg Leu CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC 2100 Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC 2145 Arg Ile Asp His Gly His His Glu Gly Val Ala Tyr Gln Ala Val ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG 2190 Thr Glu Ala Val Met Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC 2235 Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu Val Thr Ala Asp His TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC 2280 Ser His Val Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC 2325 Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA 2370 Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT 2415 Gly Val Arg Pro Asp Val Asn Glu Ser Glu Ser Gly Ser Pro Asp TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA 2460 Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser Ser Glu Thr His Gly GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG 2505 Gly Glu Asp Val Ala Val Phe Ala Arg Gly Pro Gln Ala His Leu GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC 2550 Val His Gly Val Gln Glu Gln Ser Phe Val Ala His Val Met Ala TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC TGC CTC TAG 2589 Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys Leu *** ATCTCTATAA TCTCGCGCAA CCTATTTTCC CCTCGAGAAC ACTTTTTAAG 2639 CCGTAGATAA ACAGGCTGGG ACACTTCAC ATG AGC GAA AAA TAC ATC GTC 2689 Met Ser Glu Lys Tyr Ile Val ACC TGG GAC ATG TTG CAG ATC CAT GCA CGT AAA CTC GCA AGC CGA 2734 Thr Trp Asp Met Leu Gln Ile His Ala Arg Lys Leu Ala Ser Arg CTG ATG CCT TCT GAA CAA TGG AAA GGC ATT ATT GCC GTA AGC CGT 2779 Leu Met Pro Ser Glu Gln Trp Lys Gly Ile Ile Ala Val Ser Arg GGC GGT CTG GTA CCG GGT GCG TTA CTG GCG CGT GAA CTG GGT ATT 2824 Gly Gly Leu Val Pro Gly Ala Leu Leu Ala Arg Glu Leu Gly Ile CGT CAT GTC GAT ACC GTT TGT ATT TCC AGC TAC GAT CAC GAC AAC 2869 Arg His Val Asp Thr Val Cys Ile Ser Ser Tyr Asp His Asp Asn CAG CGC GAG CTT AAA GTG CTG AAA CGC GCA GAA GGC GAT GGC GAA 2914 Gln Arg Glu Leu Lys Val Leu Lys Arg Ala Glu Gly Asp Gly Glu GGC TTC ATC GTT ATT GAT GAC CTG GTG GAT ACC GGT GGT ACT GCG 2959 Gly Phe Ile Val Ile Asp Asp Leu Val Asp Thr Gly Gly Thr Ala GTT GCG ATT CGT GAA ATG TAT CCA AAA GCG CAC TTT GTC ACC ATC 3004 Val Ala Ile Arg Glu Met Tyr Pro Lys Ala His Phe Val Thr Ile TTC GCA AAA CCG GCT GGT CGT CCG CTG GTT GAT GAC TAT GTT GTT 3049 Phe Ala Lys Pro Ala Gly Arg Pro Leu Val Asp Asp Tyr Val Val GAT ATC CCG CAA GAT ACC TGG ATT GAA CAG CCG TGG GAT ATG GGC 3094 Asp Ile Pro Gln Asp Thr Trp Ile Glu Gln Pro Trp Asp Met Gly GTC GTA TTC GTC CCG CCA ATC TCC GGT CGC TAA 3127 Val Val Phe Val Pro Pro Ile Ser Gly Arg *** 配列番号：１０ 配列の長さ：２３７２ 配列の型：核酸 鎖の数：二本鎖 トポロジ−：直鎖状 配列 AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG 100 CCCAGACACT GGACGCTGAA CCTCGCGGAC AGTTAAGAAC CCAGGGGCCT 150 CTGCGCCTGG GCCCAGCTCT GTCCCACACC GCGGTCACAT GGCACCACCT 200 CTCTTGCAGC C TCC ACC AAG GGC CCA TCG GTC TTC CCC CTG GCA CCC 247 ?? ? Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCAG CGCTCCTGCC 562 TGGACGCATC CCGGCTATGC AGCCCCAGTC CAGGGCAGCA AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GGT GGC 911 Glu Pro Lys Ser Cys Gly Gly GGC GGT TCA GGC GGT GGT GGA TCT GGT GGT GGC GGG ACT AGT CCT 956 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Pro GAG GAG GAG AAC CCG GCC TTC TGG AAC CGC CAG GCA GCT GAG GCC 1001 Glu Glu Glu Asn Pro Ala Phe Trp Asn Arg Gln Ala Ala Glu Ala CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC AAG 1046 Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala Lys AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG GTG 1091 Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr Val ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG GGG 1136 Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu Gly CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT CTG 1181 Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala Leu TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA GCC 1226 Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala Ala ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG ACC 1271 Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln Thr ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG ACA 1316 Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr Thr CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA GCA 1361 Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln Ala GGA AAG TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC GCC 1406 Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His Ala TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG TAC 1451 Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC CAG 1496 Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG ATC 1541 Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA GAC 1586 Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro Asp CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG GAC 1631 Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu Asp GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT GCC 1676 Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly Ala TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG GAC 1721 Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu Asp CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC ACG 1766 Gln Ser Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp Thr AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG ATG 1811 Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu Met GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC CGC 1856 Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro Arg GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT CAT 1901 Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly His CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG TTC 1946 His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met Phe GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG GAC 1991 Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu Asp ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC TTT 2036 Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser Phe GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC CCC 2081 Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala Pro AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC GGC 2126 Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr Gly AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC GTG 2171 Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp Val AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG GCG 2216 Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala Ala GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG GTG 2261 Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala Val TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG GAG 2306 Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln Glu CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG GAG 2351 Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu Glu CCC TAC ACG GCC TGC CTC TAG 2372 Pro Tyr Thr Ala Cys Leu ***[Sequence listing] SEQ ID NO: 1 Sequence length: 1587 Sequence type: Number of nucleic acid strands: Double-stranded topology-: Linear sequence ATG CAG GGG CCC TGG GTG CTG CTG CTG CTG GGC CTG AGG CTA CAG 45 Met Gln Gly Pro Trp Val Leu Leu Leu Leu Gly Leu Arg Leu Gln CTC TCC CTG GGC GTC ATC CCA GCT GAG GAG GAG AAC CCG GCC TTC 90 Leu Ser Leu Gly Val Ile Pro Ala Glu Glu Glu Asn Pro Ala Phe TGG AAC CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC AAG AAG CTG 135 Trp Asn Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala Lys Lys Leu CAG CCC ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC 180 Gln Pro Ile Gln Lys Val Ala Lys Asn Leu Ile Leu Phe Leu Gly GAT GGG TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG 225 Asp Gly Leu Gly Val Pro Thr Val Thr Ala Thr Arg Ile Leu Lys GGG CAG AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG 270 Gly Gln Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro Leu Ala Met GAC CGC TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC 315 Asp Arg Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp AGA CAG GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC 360 Arg Gln Val Pro Asp Ser Ala Ala Thr Ala Thr Ala Tyr L eu Cys GGG GTC AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC 405 Gly Val Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala CGC TTT AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC 450 Arg Phe Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu Val Ile Ser GTG ATG AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG 495 Val Met Asn Arg Ala Lys Gln Ala Gly Lys Ser Val Gly Val Val ACC ACC ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA 540 Thr Thr Thr Arg Val Gln His Ala Ser Pro Ala Gly Thr Tyr Ala CAC ACA GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC 585 His Thr Val Asn Arg Asn Trp Tyr Arg Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala TCA GCC CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC 630 Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile TCC AAC ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC 675 Ser Asn Met Asp Ile Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr ATG TTT CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC 720 Met Phe Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala A GC CAG AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA 765 Ser Gln Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu Val Gln Glu TGG CTG GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT 810 Trp Leu Ala Lys His Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr GAG CTC ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG 855 Glu Leu Met Gln Ala Ser Leu Asp Gln Ser Val Thr His Leu Met GGC CTC TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC 900 Gly Leu Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp CCC ACA CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG 945 Pro Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu CGC CTG CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG 990 Arg Leu Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu GGC GGC CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG 1035 Gly Gly Arg Ile Asp His Gly His His Glu Gly Val Ala Tyr Gln GCA GTC ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG 1080 Ala Val Thr Glu Ala Val Met Phe Asp Asp Ala Ile Glu Arg Ala GGC CA G CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT 1125 Gly Gln Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu Val Thr Ala GAC CAC TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG 1170 Asp His Ser His Val Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly AGC TCC ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA 1215 Ser Ser Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys GCC TAC ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC 1260 Ala Tyr Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe AAC TCA GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC 1305 Asn Ser Gly Val Arg Pro Asp Val Asn Glu Ser Glu Ser Gly Ser CCC GAT TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC 1350 Pro Asp Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser Ser Glu Thr CAC GGA GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG 1395 His Gly Gly Glu Asp Val Ala Val Phe Ala Arg Gly Pro Gln Ala CAC CTG GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC 1440 His Leu Val His Gly Val Gln Glu Gln Ser Phe Val Ala His Val ATG GC C TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC TGC GAC CTG 1485 Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys Asp Leu GCG CTC CCC GCC TGC ACC ACC GAC GCC GCG CAC CCA GTT GCC GCG 1530 Ala Leu Pro Ala Cys Thr Thr Asp Ala Ala His Pro Val Ala Ala TCG CTG CCA CTG CTG GCC GGG ACC CTG CTG CTG CTG GGG GCG TCC 1575 Ser Leu Pro Leu Leu Ala Gly Thr Leu Leu Leu Leu Gly Ala Ser GCT GCT CCC TGA 1587 Ala Ala Pro *** SEQ ID: 2 Array length: 2009 Array type: Number of nucleic acid strands: Double-stranded topology-: Linear Sequence AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGAG ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu GCA CCC TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC 286 Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly TGC CTG GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG 331 Cys Leu Val Lys AspTyr Phe Pro Glu Pro Val Thr Val Ser Trp AAC TCA GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC 376 Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val CTA CAG TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG 421 Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val CCC TCC AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT 466 Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn CAC AAG CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCGCC CGCTGATGCCTG562 AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA ACCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTG C 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp Lys ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC Pro Gly Glu CCA TTC Pro Ghealu Pro Lys CCC AAG GAC ACC CTC ATG ATC TCC CGG ACC CCT GAG GTC ACA TGC 1146 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys GTG GTG GTG GAC GTG AGC CAC GAA GAC CCT GAG GTC AAG TTC AAC 1191 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn TGG TAC GTG GAC GGC GTG GAG GTG CAT AAT GCC AAG ACA AAG CCG 1236 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro CGG GAG G AG CAG TAC AAC AGC ACG TAC CGG GTG GTC AGC GTC CTC 1281 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu ACC GTC CTG CAC CAG GAC TGG CTG AAT GGC AAG GAG TAC AAG TGC 1326 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys AAG GTC TCC AAC AAA GCC CTC CCA GCC CCC ATC GAG AAA ACC ATC 1371 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile TCC AAA GCC AAA GGTGGGACCC GTGGGGCGACAGAGCCACAT Ser Lys Ala Lys CGGCTCGGCC CACCCTCTGC CCTGAGAGTG ACCGCTGTAC CAACCTCTGT 1473 CCTACA GGG CAG CCC CGA GAA CCA CAG GTG TAC ACC CTG CCC CCA 1518 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thru Le Pro Pro TCC CGG GAT GAG AAC CAG GAT GAG AAG CTG ACC TGC CTG 1563 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu GTC AAA GGC TTC TAT CCC AGC GAC ATC GCC GTG GAG TGG GAG AGC 1608 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AAT GGG CAG CCG GAG AAC AAC TAC AAG ACC ACG CCT CCC GTG CTG 1653 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu GA C TCC GAC GGC TCC TTC TTC CTC TAC AGC AAG CTC ACC GTG GAC 1698 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp AAG AGC AGG TGG CAG CAG GGG AAC GTC TTC TCA TGC TCC GTG ATG 1743 Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met CAT GAG GCT CTG CAC AAC CAC TAC ACG CAG AAG AGC CTC TCC CTG 1788 His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu TCT CCG GGT AAA TGA GTGCGACGGC CGGCAAGCCC CGCTCCCCGG 1833 Ser Pro Gly Lys *** GCTCTCGCGG TCGCACGAGG ATGCTTGGCA CGTACCCCCT GTACATACTT 1883 CCCGGGCGCC CAGCATGGAA ATAAAGCACC CAGCGCTGCC CTGGGCCCCT 1933 GCGAGACTGT GATGGTTCTT TCCACGGGTC AGGCCGAGTC TGAGGCAGAG 1983 GTGAGGCAGAG 3 Sequence length: 2484 Sequence type: Number of nucleic acid strands: Double-stranded topology-: Linear array AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATG GCCCGC CTC GCCCG CTC GCCCA GCCCAGCTC GCCGCTC GCCCAGCTC GCT ? ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTCGCTG CCGACGCATCCCCGGACGCATCCC72 CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCT AACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGC AGA GCC CAA ATC TTG TGA CAA AAC TCA CAC 919 Glu Pro Lys Ser Cys Asp Lys Thr His Thr ATG CCC ACC GTG CCC AGGTAAGCCA GCCCAGGCCT CGCCCTCCAG 964 Cys Pro Pro Cys Pro CTCAAGGCGG GACAGGTGCC CTAGAGTAGC CTGCATCCAG GGACAGGCCC 1014 CAGCCGGGTG CTGACACGTC CACCTCCATC TCTTCCTCA GCA CCT GCT AGT 1065 Ala Pro Ala Ser CCT GAG GAC Trp Asn Arg Gln Ala Ala Glu GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC 1155 Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GTG GTG CCC ACG 1200 Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG 1245 Val Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT 1290 Gly Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA 1335 Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG 1380 Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG 1425 Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA 1470 Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC ACC ACA CGG GTG CAG CAC CAC 1515 Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG 1560 Ala Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC 1605 Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG 1650 Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA 1695 Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG 1740 Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT 1785 Asp Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG 1830 Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC 1875 Asp Gln Ser Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG 1920 Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC 1965 Met Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT 2010 Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG 2055 His His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG 2100 Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC 2145 Asp Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC 2190 Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC 2235 Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC 2280 Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG 2325 Val Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG 2370 Ala Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG 2415 Val Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG 2460 Glu Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu GAG CCC TAC ACG GCC TGC CTC TAG 2484 Glu Pro Tyr Thr Ala Cys Leu *** SEQ ID NO: 4 Sequence length: 2460 Array type: Number of nucleic acid strands: Double-stranded topology-: Linear array AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATG GCCCGC CTC GCCCG CTC GCCCA GCCCAGCTC GCCGCTC GCCCAGCTC GCT ? ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTCGCTG CCGACGCATCCCCGGACGCATCCC72 CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCTA ACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA ACT CAC ACA 919 Glu Pro Lys Ser Cys Asp Lys Thr His Thr TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC GCCCTCCAGC 965 Cys Pro Pro Cys Pro TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG GACAGGCCCC 1015 AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA CCT GCT AGT 1065 Ala Pro Ala Ser CCT GAG Cla Gla GLA CAAla ACC CCC GAG ACA Alu Lys Leu Gln Pro Ile Gln Lys GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG 1155 Val Ala Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC 1200 Pro Thr Val Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC 1245 Lys Leu Gly Pro Glu Thr Pro Leu Ala Met Asp Arg Phe P ro Tyr CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC 1290 Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC 1335 Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC 1380 Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC 1425 Asn Thr Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG 1470 Lys Gln Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC 1515 Gln His Ala Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG 1560 Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT 1605 Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG 1650 Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC 1695 Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC 1740 Arg Leu Asp Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG 1785 Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC 1830 Ser Leu Asp Gln Ser Val Thr His Leu Met Gly Leu Phe Glu Pro GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC 1875 Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG 1920 Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC 1965 Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG 2010 His Gly His His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC 2055 Val Met Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC 2100 Glu Glu Asp Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG 2145 Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC 2190 Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA 2235 Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG 2280 Pro Asp Val Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC 2325 Gln Ala Ala Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT 2370 Val Ala Val Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC 2415 Val Gln Glu Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala TGT CTG GAG CCC TAC ACG GCC TGC CTC TAG 2445 Cys Leu Glu Pro Tyr Thr Ala Cys Leu *** SEQ ID NO: 5 Sequence length: 3108 Array type: Number of nucleic acid sequences: Double-stranded topology-: Linear array AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGA GC ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala CCC TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC 289 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys CTG GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC 334 Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn TCA GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA 379 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu CAG TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC 424 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro TCC AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC 469 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His AAG CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCGCC CGCTGATGCG AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp Lys ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC C Pro Glu Cu Clu Clu CCA AAA Lys CCC AAG GAC ACC CTC ATG ATC TCC CGG ACC CCT GAG GTC ACA TGC 1146 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys GTG GTG GTG GAC GTG AGC CAC GAA GAC CCT GAG GTC AAG TTC AAC 1191 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn TGG TAC GTG GAC GGC GTG GAG GTG CAT AAT GCC AAG ACA AAG CCG 1236 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro CGG GAG GAG CAG TAC AAC AGC ACG TAC CGG GTG GTC AGC GTC CTC 1281 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu ACC GTC CTG CAC CAG GAC TGG CTG AAT GGC AAG GAG TAC AAG TGC 1326 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys AAG GTC TCC AAC AAA GCC CTC CCA GCC CCC ATC GAG AAA ACC ATC 1371 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile TCC AAA GCC AAA GGTGGGGGACCC GTGGGGTG23 CAGGGAGGCCAT GGA Lys Ala Lys CGGCTCGGCC CACCCTCTGC CCTGAGAGTG ACCGCTGTAC CAACCTCTGT 1473 CCTACA GGG CAG CCC CGA GAA CCA CAG GTG TAC ACC CTG CCC CCA 1518 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro TCC CGG GAT GAG CAC ACC TGC CTG 1563 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu GTC AAA GGC TTC TAT CCC AGC GAC ATC GCC GTG GAG TGG GAG AGC 1608 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AAT GGG CAG CCG GAG AAC AAC TAC AAG ACC ACG CCT CCC GTG CTG 1653 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu GAC TCC GAC GGC TCC TTC TTC CTC TAC AGC AAG CTC ACC GTG GAC 1698 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp AAG AGC AGG TGG CAG CAG GGG AAC GCT AGT CCT GAG GCC CTG GAT 1743 Lys Ser Arg Trp Gln Gln Gly Asn Ala Ser Pro Glu Ala Leu Asp GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC AAG AAC CTC 1788 Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala Lys Asn Leu ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG GTG ACA GCC 1833 Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr Val Thr Ala ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG GGG CCT GAG 1878 Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu Gly Pro Glu ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT CTG TCC AAG 1923 Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala Leu Ser Lys ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA GCC ACA GCC 1968 Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala Ala Thr Ala ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG ACC ATC GGC 2013 Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln Thr Ile Gly TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG ACA CGC GGC 2058 Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr Thr Arg Gly AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA GCA GGA AAG 2103 Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln Ala Gly Lys TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC GCC TCG CCA 2148 Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His Ala Ser Pro GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG TAC TCA GAT 2193 Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr Ser Asp GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC CAG GAC ATC 2238 Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG ATC CTT GGC 2283 Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile Leu Gly GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA GAC CCT GAG 2328 Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro Asp Pro Glu TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG GAC GGG AAG 2373 Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu Asp Gly Lys AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT GCC TGG TAT 2418 Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly Ala Trp Tyr GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG GAC CAG TCT 2463 Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu Asp Gln Ser GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC ACG AAA TAT 2508 Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp Thr Lys Tyr GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG ATG GAG ATG 2553 Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu Met Glu Met ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC CGC GGC TTC 2598 Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro Arg Gly Phe TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT CAT CAT GAG 2643 Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly His His Glu GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG TTC GAC GAC GAC 2688 Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met Phe Asp Asp GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG GAC ACG CTG 2733 Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu Asp Thr Leu ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC TTT GGT GGC 2778 Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser Phe Gly Gly TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC CCC AGC AAG 2823 Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala Pro Ser Lys GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC GGC AAT GGC 2868 Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr Gly Asn Gly CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC GTG AAT GAG 2913 Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp Val Asn Glu AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG GCG GTG CCC 2958 Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala Ala Val Pro CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG GTG TTT GCG 3003 Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ala CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG GAG CAG AGC 3048 Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln Glu Gln Ser TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG GAG CCC TAC 3093 Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr AC G GCC TGC CTC TAG 3108 Thr Ala Cys Leu *** SEQ ID NO: 6 Sequence length: 3147 Array type: Number of nucleic acid strands: Double-stranded topology-: Linear array AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATGA GC ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala CCC TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC 289 Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys CTG GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC 334 Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn TCA GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA 379 Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu CAG TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC 424 Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro TCC AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC 469 Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His AAG CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGG AGGGAGGGTG TCTGCTGGAA GCAGGCTCGCC CGCTGATGCG AGGCAGGCCC 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 7 12 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp LyS ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA GTC TTC CTC TTC C Pro Glu Cu Clu Clu CCA AAA Lys CCC AAG GAC ACC CTC ATG ATC TCC CGG ACC CCT GAG GTC ACA TGC 1146 Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys GTG GTG GTG GAC GTG AGC CAC GAA GAC CCT GAG GTC AAG TTC AAC 1191 Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn TGG TAC GTG GAC GGC GTG GAG GTG CAT AAT GCC AAG ACA AAG CCG 1236 Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro CGG GAG GAG C AG TAC AAC AGC ACG TAC CGG GTG GTC AGC GTC CTC 1281 Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu ACC GTC CTG CAC CAG GAC TGG CTG AAT GGC AAG GAG TAC AAG TGC 1326 Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys AAG GTC TCC AAC AAA GCC CTC CCA GCC CCC ATC GAG AAA ACC ATC 1371 Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile TCC AAA GCC AAA GGTGGGGGACCC GTGGGGTG23 CAGGGAGGCCAT GGA Lys Ala Lys CGGCTCGGCC CACCCTCTGC CCTGAGAGTG ACCGCTGTAC CAACCTCTGT 1473 CCTACA GGG CAG CCC CGA GAA CCA CAG GTG TAC ACC CTG CCC CCA 1518 Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro TCC CGG GAT GAG CAC ACC TGC CTG 1563 Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu GTC AAA GGC TTC TAT CCC AGC GAC ATC GCC GTG GAG TGG GAG AGC 1608 Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AAT GGG CAG CCG GAG AAC AAC TAC AAG ACC ACG CCT CCC GTG CTG 1653 Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu GAC TC C GAC GGC TCC TTC TTC CTC TAC AGC AAG CTC ACC GTG GAC 1698 Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp AAG AGC AGG TGG CAG CAG GGG AAC GCT AGT CCT GAG GAG GAG AAC 1743 Lys Ser Arg Trp Gln Gln Gly Asn Ala Ser Pro Glu Glu Glu Asn CCG GCC TTC TGG AAC CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC 1788 Pro Ala Phe Trp Asn Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC 1833 Lys Lys Leu Gln Pro Ile Gln Lys Val Ala Lys Asn Leu Ile Leu TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG 1878 Phe Leu Gly Asp Gly Leu Gly Val Pro Thrr Val Thr Ala Thr Arg ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC 1923 Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC 1968 Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC 2013 Asn Val Asp Arg Gln Val Pro Asp Ser Ala Ala Thr Ala Thr Ala TAC C TG TGC GGG GTC AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT 2058 Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG 2103 Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA 2148 Val Ile Ser Val Met Asn Arg Ala Lys Gln Ala Gly Lys Ser Val GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC 2193 Gly Val Val Thr Thr Thr Arg Val Gln His Ala Ser Pro Ala Gly ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC 2238 Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT 2283 Met Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC 2328 Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile Leu Gly Gly Gly CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA 2373 Arg Lys Tyr Met Phe Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro GCT G AT GCC AGC CAG AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG 2418 Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG 2463 Val Gln Glu Trp Leu Ala Lys His Gln Gly Ala Trp Tyr Val Trp AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC 2508 Asn Arg Thr Glu Leu Met Gln Ala Ser Leu Asp Gln Ser Val Thr CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC 2553 His Leu Met Gly Leu Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG 2598 Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC 2643 Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG 2688 Phe Val Glu Gly Gly Arg Ile Asp His Gly His His Glu Gly Val GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT 2733 Ala Tyr Gln Ala Val Thr Glu Ala Val Met Phe Asp Asp Ala Ile GAG A GG GCG GGC CAG CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC 2778 Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC 2823 Val Thr Ala Asp His Ser His Val Phe Ser Phe Gly Gly Tyr Thr TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG 2868 Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC 2913 Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG 2958 Tyr Val Phe Asn Ser Gly Val Arg Pro Asp Val Asn Glu Ser Glu AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG 3003 Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC 3048 Ser Glu Thr His Gly Gly Glu Asp Val Ala Val Phe Ala Arg Gly CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA 3093 Pro Gln Ala His Leu Val His Gly Val Gln Glu Gln Ser Phe Val GCG C AT GTC ATG GCC TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC 3138 Ala His Val Met Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala TGC CTC TAG 3147 Cys Leu *** SEQ ID NO: 7 Sequence length: 3022 Array type: Number of DNA strands: Double-stranded topology-: Linear sequence AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATC GCTCGCTC GCCGCTCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCCAGCTC ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTCGCTG CCGACGCATCCCCGGACGCATCCC72 CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCTA ACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA ACT CAC ACA 920 Glu Pro Lys Ser Cys Asp Lys Thr His Thr TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC GCCCTCCAGC 965 Cys Pro Pro Cys Pro TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG GACAGGCCCC 1015 AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA CCT GCT AGT 1065 Ala Pro Ala Ser CCT GAG Glu GTC GTC GTC GTC GTC TTC TGG Trp Asn Arg Gln Ala Ala Glu GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC 1155 Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GTG GTG CCC ACG 1200 Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG 1245 Val Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly L ys Leu GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT 1290 Gly Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA 1335 Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG 1380 Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG 1425 Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA 1470 Thr Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC ACC ACA CGG GTG CAG CAC CAC 1515 Ala Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG 1560 Ala Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC 1605 Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu G ly Cys CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG 1650 Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA 1695 Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG 1740 Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT 1785 Asp Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG 1830 Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC 1875 Asp Gl nSer Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG 1920 Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC 1965 Met Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT 2010 Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG 2055 His His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG 2100 Phe Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC 2145 Asp Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC 2190 Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC 2235 Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC 2280 Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG 2325 Val Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG 2370 Ala Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG 2415 Val Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG 2460 Glu Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu GAG CCC TAC ACG GCC TGC CTC TAG ATCTCTATAA TCTCGCGCGCAA 2504 Glu Pro Tyr Thr Ala Cys Leu *** CCTATTTTCC CCTCGAGAAC ACTTTTTAAG CCGTAGATAA ACAGGCTGGG 2554 ACACTTCAC ATG AGC GAA AAA TAC ATC GTC ACC TGG GAC ATG TTG 2599 Met Ser Glu Lyt Tup As CAT GCA CGT AAA CTC GCA AGC CGA CTG ATG CCT TCT GAA 2644 Gln Ile His Ala Arg Lys Leu Ala Ser Arg Leu Met Pro Ser Glu CAA TGG AAA GGC ATT ATT GCC GTA AGC CGT GGC GGT CTG GTA CCG 2689 Gln Trp Lys Gly Ile Ile Ala Val Ser Arg Gly Gly Leu Val Pro GGT GCG TTA CTG GCG CGT GAA CTG GGT ATT CGT CAT GTC GAT ACC 2734 Gly Ala Leu Leu Ala Arg Glu Leu Gly Ile Arg His Val Asp Thr GTT TGT ATT TCC AGC TAC GAT CAC GAC AAC CAG CGC GAG CTT AAA 2779 Val Cys Ile Ser Ser Tyr Asp His Asp Asn Gln Arg Glu Leu Lys GTG CTG AAA CGC GCA GAA GGC GAT GGC GAA GGC TTC ATC GTT ATT 2824 Val Leu Lys Arg Ala Glu Gly Asp Gly Glu Gly Phe Ile Val Ile GAT GAC CTG GTG GAT ACC GGT GGT ACT GCG GTT GCG ATT CGT GAA 2869 Asp Asp Leu Val Asp Thr Gly Gly Thr Ala Val Ala Ile Arg Glu ATG TAT CCA AAA GCG CAC TTT GTC ACC ATC TTC GCA AAA CCG GCT 2914 Met Tyr Pro Lys Ala His Phe Val Thr Ile Phe Ala Lys Pro Ala GGT CGT CCG CTG GTT GAT GAC TAT GTT GTT GAT ATC CCG CAA GAT 2959 Gly Arg Pro Leu Val Asp Asp Tyr Val Val Asp Ile Pro Gln Asp ACC TGG ATT GAA CAG CCG TGG GAT ATG GGC GTC GTA TTC GTC CCG 3004 Thr Trp Ile Glu Gln Pro Trp Asp Met Gly Val Val Phe Val Pro CCA ATC TCC GGT CGC TAA 3022 Pro Ile Ser Gly Arg *** SEQ ID NO: 8 Sequence length: 3076 Array type: Number of nucleic acid strands: Double-stranded topology-: Linear sequence AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATC GCTCGCTC GCCGCTCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCCAGCTC ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGGAGGGAGAGGGTG TCTGCTGGAA GCAGGCTCAGCCGCGCTCGCGCC562 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 CCCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA 911 Glu Pro Lys Ser Cys Asp Lys ACT CAC ACA TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC 955 Thr His Thr Cys Pro Pro Cys Pro GCCCTCCAGC TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG 1005 GACAGGCCCC AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA 1056 Ala CCT GAA CTC CTG GGG GGA CCG TCA Prolyshe Pro1 Leu1 CCC AAG GAC GTC ATC CCA GCT GAG GAG GAG AAC CCG GCC TTC TGG 1146 Pro Lys Asp Val Ile Pro Ala Glu Glu Glu Asn Pro Ala Phe Trp AAC CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC AAG AAG CTG CAG 1191 Asn Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala Lys Lys Leu Gln CCC ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC GAT 1236 Pro Ile Gln Lys Val Ala Lys Asn Leu Ile Leu Phe Leu Gly Asp GGG TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG GGG 1281 Gly Leu Gly Val Pro Thr Val Thr Ala Thr Arg Ile Leu Lys Gly CAG AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG GAC 1326 Gln Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro Leu Ala Met Asp CGC TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC AGA 1371 Arg Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp Arg CAG GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC GGG 1416 Gln Val Pro Asp Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys Gly GTC AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC CGC 1461 Val Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg TTT AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC GTG 1506 Phe Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu Val Ile Ser Val ATG AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG ACC 1551 Met Asn Arg Ala Lys Gln Ala Gly Lys Ser Val Gly Val Val Thr ACC ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC ACC TAC TAC GCA CAC 1596 Thr Thr Arg Val Gln His Ala Ser Pro Ala Gly Thr Tyr Ala His ACA GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC TCA 1641 Thr Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala Ser GCC CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC TCC 1686 Ala Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile Ser AAC ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC ATG 1731 Asn Met Asp Ile Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr Met TTT CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC AGC 1776 Phe Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala Ser CAG AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA TGG 1821 Gln Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu Val Gln Glu Trp CTG GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT GAG 1866 Leu Ala Lys His Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr Glu CTC ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG GGC 1911 Leu Met Gln Ala Ser Leu Asp Gln Ser Val Thr His Leu Met Gly CTC TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC CCC 1956 Leu Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp Pro ACA CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG CGC 2001 Thr Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg CTG CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG GGC 2046 Leu Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu Gly GGC CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG GCA 2091 Gly Arg Ile Asp His Gly His His Glu Gly Val Ala Tyr Gln Ala GTC ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG GGC 2136 Val Thr Glu Ala Val Met Phe Asp Asp Ala Ile Glu Arg Ala Gly CAG CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT GAC 2181 Gln Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu Val Thr Ala Asp CAC TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG AGC 2226 His Ser His Val Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly Ser TCC ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA GCC 2271 Ser Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys Ala TAC ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC AAC 2316 Tyr Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe Asn TCA GGC GTG CG A CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC CCC 2361 Ser Gly Val Arg Pro Asp Val Asn Glu Ser Glu Ser Gly Ser Pro GAT TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC CAC 2406 Asp Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser Ser Glu Thr His GGA GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG CAC 2451 Gly Gly Glu Asp Val Ala Val Phe Ala Arg Gly Pro Gln Ala His CTG GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC ATG 2496 Leu Val His Gly Val Gln Glu Gln Ser Phe Val Ala His Val Met GCC TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC TGC CTC TAG 2538 Ala Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys Leu * ** ATCTCTATAA TCTCGCGCAA CCTATTTTCC CCTCGAGAAC ACTTTTTAAG 2588 CCGTAGATAA ACAGGCTGGG ACACTTCAC ATG AGC GAA AAA TAC ATC GTC 2638 Met Ser Glu Lys Tyr Ile Val ACC TGG GAC ATG TTG CAG ATC Tle CAGle Au CTC G683 Au Ala Arg Lys Leu Ala Ser Arg CTG ATG CCT TCT GAA CAA TGG AAA GGC ATT ATT GCC GTA AGC CGT 2728 Leu Met Pro Ser Glu Gln Trp Lys Gly Ile Ile Ala Val Se r Arg GGC GGT CTG GTA CCG GGT GCG TTA CTG GCG CGT GAA CTG GGT ATT 2773 Gly Gly Leu Val Pro Gly Ala Leu Leu Ala Arg Glu Leu Gly Ile CGT CAT GTC GAT ACC GTT TGT ATT TCC AGC TAC GAT CAC GAC AAC 2818 Arg His Val Asp Thr Val Cys Ile Ser Ser Tyr Asp His Asp Asn CAG CGC GAG CTT AAA GTG CTG AAA CGC GCA GAA GGC GAT GGC GAA 2863 Gln Arg Glu Leu Lys Val Leu Lys Arg Ala Glu Gly Asp Gly Glu GGC TTC ATC GTT ATT GAT GAC CTG GTG GAT ACC GGT GGT ACT GCG 2908 Gly Phe Ile Val Ile Asp Asp Leu Val Asp Thr Gly Gly Thr Ala GTT GCG ATT CGT GAA ATG TAT CCA AAA GCG CAC TTT GTC ACC ATC 2953 Val Ala Ile Arg Glu Met Tyr Pro Lys Ala His Phe Val Thr Ile TTC GCA AAA CCG GCT GGT CGT CCG CTG GTT GAT GAC TAT GTT GTT 2998 Phe Ala Lys Pro Ala Gly Arg Pro Leu Val Asp Asp Tyr Val Val GAT ATC CCG CAA GAT ACC TGG ATT GAA CAG CCG TGG GAT ATG GGC 3043 Asp Ile Pro Gln Asp Thr Trp Ile Glu Gln Pro Trp Asp Met Gly GTC GTA TTC GTC CCG CCA ATC TCC GGT CGC TAA 3076 Val Val Phe Val Pro Pro Ile Ser Gly Arg *** SEQ ID NO: 9 Sequence length: 3127 Array type: Number of nucleic acid strands: Double-stranded topology-: Linear sequence AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATC GCTCGCTC GCCGCTCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCCAGCTC ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC CAGCACAGGG 522 Pro Ser Asn Thr Lys Val Asp Lys Lys Val AGGGAGGGTCGCTG CCGACGCATCCCCGGACGCATCCC72 CGTCTGCCTC 622 TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA GAGGGTCTTC 672 TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC CCCT AACCCA 722 GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG CCAAGAGCCA 772 TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA AGGCCAAACT 822 CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT TCCAGTAACT 872 CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GAC AAA ACT CAC ACA 920 Glu Pro Lys Ser Cys Asp Lys Thr His Thr TGC CCA CCG TGC CCA GGTAAGCCAG CCCAGGCCTC GCCCTCCAGC 965 Cys Pro Pro Cys Pro TCAAGGCGGG ACAGGTGCCC TAGAGTAGCC TGCATCCAGG GACAGGCCCC 1015 AGCCGGGTGC TGACACGTCC ACCTCCATCT CTTCCTCA GCA CCT GAA CTC 1065 Ala Pro Glu Leu CTG GCC CTC GAG CCG TCA CCC CTC Phe Pro Pro Lys Pro Lys Asp GTC GGT GGC GGC GGT TCA GGC GGT GGT GGA TCT GGT GGT GGC GGG 1155 Val Gly Gly Gly Gly Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly TCA GAC GTC ATC CCA GCT GAG GAG GAG AAC CCG GCC TTC TGG AAC 1200 Ser Asp Val Ile Pro Ala Glu Glu Glu Asn Pro Ala Phe Trp Asn CGC CAG GCA GCT GAG GCC CTG GAT GCT GCC AAG AAG CTG CAG CCC 1245 Arg Gln Ala Ala Glu Ala Leu Asp Ala Ala Lys Lys Leu Gln Pro ATC CAG AAG GTC GCC AAG AAC CTC ATC CTC TTC CTG GGC GAT GGG 1290 Ile Gln Lys Val Ala Lys Asn Leu Ile Leu Phe Leu Gly Asp Gly TTG GGG GTG CCC ACG GTG ACA GCC ACC AGG ATC CTA AAG GGG CAG 1335 Leg Gly Val Pro Thr Val Thr Ala Thr Arg Ile Leu Lys Gly Gln AAG AAT GGC AAA CTG GGG CCT GAG ACG CCC CTG GCC ATG GAC CGC 1380 Lys Asn Gly Lys Leu Gly Pro Glu Thr Pro Leu Ala Met Asp Arg TTC CCA TAC CTG GCT CTG TCC AAG ACA TAC AAT GTG GAC AGA CAG 1425 Phe Pro Tyr Leu Ala Leu Ser Lys Thr Tyr Asn Val Asp Arg Gln GTG CCA GAC AGC GCA GCC ACA GCC ACG GCC TAC CTG TGC GGG GTC 1470 Val Pro Asp Ser Ala Ala Thr Ala Thr Ala Tyr Leu Cys Gly Val AAG GCC AAC TTC CAG ACC ATC GGC TTG AGT GCA GCC GCC CGC TTT 1515 Lys Ala Asn Phe Gln Thr Ile Gly Leu Ser Ala Ala Ala Arg Phe AAC CAG TGC AAC ACG ACA CGC GGC AAT GAG GTC ATC TCC GTG ATG 1560 Asn Gln Cys Asn Thr Thr Arg Gly Asn Glu Val Ile Ser Val Met AAC CGG GCC AAG CAA GCA GGA AAG TCA GTA GGA GTG GTG ACC ACC 1605 Asn Arg Ala Lys Gln Ala Gly Lys Ser Val Gly Val Val Thr Thr ACA CGG GTG CAG CAC GCC TCG CCA GCC GGC ACC TAC GCA CAC ACA 1650 Thr Arg Val Gln His Ala Ser Pro Ala Gly Thr Tyr Ala His Thr GTG AAC CGC AAC TGG TAC TCA GAT GCT GAC ATG CCT GCC TCA GCC 1695 Val Asn Arg Asn Trp Tyr Ser Asp Ala Asp Met Pro Ala Ser Ala CGC CAG GAG GGG TGC CAG GAC ATC GCC ACT CAG CTC ATC TCC AAC 1740 Arg Gln Glu Gly Cys Gln Asp Ile Ala Thr Gln Leu Ile Ser Asn ATG GAC ATT GAC GTG ATC CTT GGC GGA GGC CGC AAG TAC ATG TTT 1785 Met Asp Ile Asp Val Ile Leu Gly Gly Gly Arg Lys Tyr Met Phe CCC ATG GGG ACC CCA GAC CCT GAG TAC CCA GCT GAT GCC AGC CAG 1830 Pro Met Gly Thr Pro Asp Pro Glu Tyr Pro Ala Asp Ala Ser Gln AAT GGA ATC AGG CTG GAC GGG AAG AAC CTG GTG CAG GAA TGG CTG 1875 Asn Gly Ile Arg Leu Asp Gly Lys Asn Leu Val Gln Glu Trp Leu GCA AAG CAC CAG GGT GCC TGG TAT GTG TGG AAC CGC ACT GAG CTC 1920 Ala Lys His Gln Gly Ala Trp Tyr Val Trp Asn Arg Thr Glu Leu ATG CAG GCG TCC CTG GAC CAG TCT GTG ACC CAT CTC ATG GGC CTC 1965 Met Gln Ala Ser Leu Asp Gln Ser Val Thr His Leu Met Gly Leu TTT GAG CCC GGA GAC ACG AAA TAT GAG ATC CTC CGA GAC CCC ACA 2010 Phe Glu Pro Gly Asp Thr Lys Tyr Glu Ile Leu Arg Asp Pro Thr CTG GAC CCC TCC CTG ATG GAG ATG ACA GAG GCT GCC CTG CGC CTG 2055 Leu Asp Pro Ser Leu Met Glu Met Thr Glu Ala Ala Leu Arg Leu CTG AGC AGG AAC CCC CGC GGC TTC TAC CTC TTT GTG GAG GGC GGC 2100 Leu Ser Arg Asn Pro Arg Gly Phe Tyr Leu Phe Val Glu Gly Gly CGC ATC GAC CAT GGT CAT CAT GAG GGT GTG GCT TAC CAG GCA GTC 2145 Arg Ile Asp His Gly His His Glu Gly Val Ala Tyr Gln Ala Val ACT GAG GCG GTC ATG TTC GAC GAC GCC ATT GAG AGG GCG GGC CAG 2190 Thr Glu Ala Val Met Phe Asp Asp Asp Ala Ile Glu Arg Ala Gly Gln CTC ACC AGC GAG GAG GAC ACG CTG ACC CTC GTC ACC GCT GAC CAC 2235 Leu Thr Ser Glu Glu Asp Thr Leu Thr Leu Val Thr Ala Asp His TCC CAT GTC TTC TCC TTT GGT GGC TAC ACC TTG CGA GGG AGC TCC 2280 Ser His Val Phe Ser Phe Gly Gly Tyr Thr Leu Arg Gly Ser Ser ATC TTC GGG TTG GCC CCC AGC AAG GCT CAG GAC AGC AAA GCC TAC 2325 Ile Phe Gly Leu Ala Pro Ser Lys Ala Gln Asp Ser Lys Ala Tyr ACG TCC ATC CTG TAC GGC AAT GGC CCG GGC TAC GTG TTC AAC TCA 2370 Thr Ser Ile Leu Tyr Gly Asn Gly Pro Gly Tyr Val Phe Asn Ser GGC GTG CGA CCA GAC GTG AAT GAG AGC GAG AGC GGG AGC CCC GAT 2415 Gly Val Arg Pro Asp Val Asn Glu Ser Glu Ser Gly Ser Pro Asp TAC CAG CAG CAG GCG GCG GTG CCC CTG TCG TCC GAG ACC CAC GGA 2460 Tyr Gln Gln Gln Ala Ala Val Pro Leu Ser Ser Glu Thr His Gly GGC GAA GAC GTG GCG GTG TTT GCG CGC GGC CCG CAG GCG CAC CTG 2505 Gly Glu Asp Val Ala Val Phe Ala Arg Gly Pro Gln Ala His Leu GTG CAT GGT GTG CAG GAG CAG AGC TTC GTA GCG CAT GTC ATG GCC 2550 Val His Gly Val Gln Glu Gln Ser Phe Val Ala His Val Met Ala TTC GCT GCC TGT CTG GAG CCC TAC ACG GCC TGC CTC TAG 2589 Phe Ala Ala Cys Leu Glu Pro Tyr Thr Ala Cys Leu *** ATCTCTATAA TCTCGCGCAA CCTATTTTCC CCTCGAGAAC ACTTTTTAAG 2639 CCGTAGTACAACACAGGC ATC GTC 2689 Met Ser Glu Lys Tyr Ile Val ACC TGG GAC ATG TTG CAG ATC CAT GCA CGT AAA CTC GCA AGC CGA 2734 Thr Trp Asp Met Leu Gln Ile His Ala Arg Lys Leu Ala Ser Arg CTG ATG CCT TCT GAA CAA TGG AAA GGC ATT ATT GCC GTA AGC CGT 2779 Leu Met Pro Ser Glu Gln Trp Lys Gly Ile Ile Ala Val Ser Arg GGC GGT CTG GTA CCG GGT GCG TTA CTG GCG CGT GAA CTG GGT ATT 2824 Gly Gly Leu Val Pro Gly Ala Leu Leu Ala Arg Glu Leu Gly Ile CGT CAT GTC GAT ACC GTT TGT ATT TCC AGC TAC GAT CAC GAC AAC 2869 Arg His Val Asp Thr Val Cys Ile Ser Ser Tyr Asp His Asp Asn CAG CGC GAG CTT AAA GTG CTG AAA CGC GCA GAA GGC GAT GGC GAA 2914 Gln Arg Glu Leu Lys Val Leu Lys Arg Ala Glu Gly Asp Gly Glu GGC TTC ATC GTT ATT GAT GAC CTG GTG GAT ACC GGT GGT ACT GCG 2959 Gly Phe Ile Val Ile Asp Asp Leu Val Asp Thr Gly Gly Thr Ala GTT GCG ATT CGT GAA ATG TAT CCA AAA GCG CAC TTT GTC ACC ATC 3004 Val Ala Ile Arg Glu Met Tyr Pro Lys Ala His Phe Val Thr Ile TTC GCA AAA CCG GCT GGT CGT CCG CTG GTT GAT GAC TAT GTT GTT 3049 Phe Ala Lys Pro Ala Gly Arg Pro Leu Val Asp Asp Tyr Val Val GAT ATC CCG CAA GAT ACC TGG ATT GAA CAG CCG TGG GAT ATG GGC 3094 Asp Ile Pro Gln Asp Thr Trp Ile Glu Gln Pro Trp Asp Met Gly GTC GTA TTC GTC CCG CCA ATC TCC GGT CGC TAA 3127 Val Val Phe Val Pro Pro Ile Ser Gly Arg *** SEQ ID NO: 10 Sequence length: 2372 Array Type: Number of nucleic acid strands: Double-stranded topology-: Linear sequence AGCTTTCTGG GGCAGGCCAG GCCTGACCTT GGCTTTGGGG CAGGGAGGGG 50 GCTAAGGTGA GGCAGGTGGC GCCAGCAGGT GCACACCCAA TGCCCATC GCTCGCTC GCCGCTCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCGCCAGCTC ?  ?  Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro TCC TCC AAG AGC ACC TCT GGG GGC ACA GCG GCC CTG GGC TGC CTG 292 Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu GTC AAG GAC TAC TTC CCC GAA CCG GTG ACG GTG TCG TGG AAC TCA 337 Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser GGC GCC CTG ACC AGC GGC GTG CAC ACC TTC CCG GCT GTC CTA CAG 382 Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln TCC TCA GGA CTC TAC TCC CTC AGC AGC GTG GTG ACC GTG CCC TCC 427 Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser AGC AGC TTG GGC ACC CAG ACC TAC ATC TGC AAC GTG AAT CAC AAG 472 Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys CCC AGC AAC ACC AAG GTG GAC AAG AAA GTT GGTGAGAGGC 512 Pro Ser Asn Thr Lys Val Asp Lys Lys Val CAGCACAGGGAGGGAGAGGGTG TCTGCTGGAA GCAGGCTCAGCCGCGCTCGCGCC562 612 CGTCTGCCTC TTCACCCGGA GCCTCTGCCC GCCCCACTCA TGCTCAGGGA 662 GAGGGTCTTC TGGCTTTTTC CCAGGCTCTG GGCAGGCACA GGCTAGGTGC 712 C CCTAACCCA GGCCCTGCAC ACAAAGGGGC AGGTGCTGGG CTCAGACCTG 762 CCAAGAGCCA TATCCGGGAG GACCCTGCCC CTGACCTAAG CCCACCCCAA 812 AGGCCAAACT CTCCACTCCC TCAGCTCGGA CACCTTCTCT CCTCCCAGAT 862 TCCAGTAACT CCCAATCTTC TCTCTGCA GAG CCC AAA TCT TGT GGT GGC 911 Glu Pro Lys Ser Cys Gly Gly GGC GGT TCA GGC GGT GGT GGA TCT GGT GGT GGC GGG ACT AGT CCT 956 Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Thr Pro GAG GAG GAG AAC CCG GCC TTC TGG AAC CGC CAG GCA GCT GAG GCC 1001 Glu Glu Glu Asn Pro Ala Phe Trp Asn Arg Gln Ala Ala Glu Ala CTG GAT GCT GCC AAG AAG CTG CAG CCC ATC CAG AAG GTC GCC AAG 1046 Leu Asp Ala Ala Lys Lys Leu Gln Pro Ile Gln Lys Val Ala Lys AAC CTC ATC CTC TTC CTG GGC GAT GGG TTG GGG GTG CCC ACG GTG 1091 Asn Leu Ile Leu Phe Leu Gly Asp Gly Leu Gly Val Pro Thr Val ACA GCC ACC AGG ATC CTA AAG GGG CAG AAG AAT GGC AAA CTG GGG 1136 Thr Ala Thr Arg Ile Leu Lys Gly Gln Lys Asn Gly Lys Leu Gly CCT GAG ACG CCC CTG GCC ATG GAC CGC TTC CCA TAC CTG GCT CTG 1181 Pro Glu Thr Pro Leu Ala Met Asp Arg Phe Pro Tyr Leu Ala Leu TCC AAG ACA TAC AAT GTG GAC AGA CAG GTG CCA GAC AGC GCA GCC 1226 Ser Lys Thr Tyr Asn Val Asp Arg Gln Val Pro Asp Ser Ala Ala ACA GCC ACG GCC TAC CTG TGC GGG GTC AAG GCC AAC TTC CAG ACC 1271 Thr Ala Thr Ala Tyr Leu Cys Gly Val Lys Ala Asn Phe Gln Thr ATC GGC TTG AGT GCA GCC GCC CGC TTT AAC CAG TGC AAC ACG ACA 1316 Ile Gly Leu Ser Ala Ala Ala Arg Phe Asn Gln Cys Asn Thr Thr CGC GGC AAT GAG GTC ATC TCC GTG ATG AAC CGG GCC AAG CAA GCA 1361 Arg Gly Asn Glu Val Ile Ser Val Met Asn Arg Ala Lys Gln Ala GGA AAG TCA GTA GGA GTG GTG ACC ACC ACA CGG GTG CAG CAC GCC 1406 Gly Lys Ser Val Gly Val Val Thr Thr Thr Arg Val Gln His Ala TCG CCA GCC GGC ACC TAC GCA CAC ACA GTG AAC CGC AAC TGG TAC 1451 Ser Pro Ala Gly Thr Tyr Ala His Thr Val Asn Arg Asn Trp Tyr TCA GAT GCT GAC ATG CCT GCC TCA GCC CGC CAG GAG GGG TGC CAG 1496 Ser Asp Ala Asp Met Pro Ala Ser Ala Arg Gln Glu Gly Cys Gln GAC ATC GCC ACT CAG CTC ATC TCC AAC ATG GAC ATT GAC GTG ATC 1541 Asp Ile Ala Thr Gln Leu Ile Ser Asn Met Asp Ile Asp Val Ile CTT GGC GGA GGC CGC AAG TAC ATG TTT CCC ATG GGG ACC CCA GAC 1586 Leu Gly Gly Gly Arg Lys Tyr Met Phe Pro Met Gly Thr Pro Asp CCT GAG TAC CCA GCT GAT GCC AGC CAG AAT GGA ATC AGG CTG GAC 1631 Pro Glu Tyr Pro Ala Asp Ala Ser Gln Asn Gly Ile Arg Leu Asp GGG AAG AAC CTG GTG CAG GAA TGG CTG GCA AAG CAC CAG GGT GCC 1676 Gly Lys Asn Leu Val Gln Glu Trp Leu Ala Lys His Gln Gly Ala TGG TAT GTG TGG AAC CGC ACT GAG CTC ATG CAG GCG TCC CTG GAC 1721 Trp Tyr Val Trp Asn Arg Thr Glu Leu Met Gln Ala Ser Leu Asp CAG TCT GTG ACC CAT CTC ATG GGC CTC TTT GAG CCC GGA GAC ACG 1766 Gln Ser Val Thr His Leu Met Gly Leu Phe Glu Pro Gly Asp Thr AAA TAT GAG ATC CTC CGA GAC CCC ACA CTG GAC CCC TCC CTG ATG 1811 Lys Tyr Glu Ile Leu Arg Asp Pro Thr Leu Asp Pro Ser Leu Met GAG ATG ACA GAG GCT GCC CTG CGC CTG CTG AGC AGG AAC CCC CGC 1856 Glu Met Thr Glu Ala Ala Leu Arg Leu Leu Ser Arg Asn Pro Arg GGC TTC TAC CTC TTT GTG GAG GGC GGC CGC ATC GAC CAT GGT CAT 1901 Gly Phe Tyr Leu Phe Val Glu Gly Gly Arg Ile Asp His Gly His CAT GAG GGT GTG GCT TAC CAG GCA GTC ACT GAG GCG GTC ATG TTC 1946 His Glu Gly Val Ala Tyr Gln Ala Val Thr Glu Ala Val Met Phe GAC GAC GCC ATT GAG AGG GCG GGC CAG CTC ACC AGC GAG GAG GAC 1991 Asp Asp Ala Ile Glu Arg Ala Gly Gln Leu Thr Ser Glu Glu Asp ACG CTG ACC CTC GTC ACC GCT GAC CAC TCC CAT GTC TTC TCC TTT 2036 Thr Leu Thr Leu Val Thr Ala Asp His Ser His Val Phe Ser Phe GGT GGC TAC ACC TTG CGA GGG AGC TCC ATC TTC GGG TTG GCC CCC 2081 Gly Gly Tyr Thr Leu Arg Gly Ser Ser Ile Phe Gly Leu Ala Pro AGC AAG GCT CAG GAC AGC AAA GCC TAC ACG TCC ATC CTG TAC GGC 2126 Ser Lys Ala Gln Asp Ser Lys Ala Tyr Thr Ser Ile Leu Tyr Gly AAT GGC CCG GGC TAC GTG TTC AAC TCA GGC GTG CGA CCA GAC GTG 2171 Asn Gly Pro Gly Tyr Val Phe Asn Ser Gly Val Arg Pro Asp Val AAT GAG AGC GAG AGC GGG AGC CCC GAT TAC CAG CAG CAG GCG GCG 2216 Asn Glu Ser Glu Ser Gly Ser Pro Asp Tyr Gln Gln Gln Ala Ala GTG CCC CTG TCG TCC GAG ACC CAC GGA GGC GAA GAC GTG GCG GTG 2261 Val Pro Leu Ser Ser Glu Thr His Gly Gly Glu Asp Val Ala Val TTT GCG CGC GGC CCG CAG GCG CAC CTG GTG CAT GGT GTG CAG GAG 2306 Phe Ala Arg Gly Pro Gln Ala His Leu Val His Gly Val Gln Glu CAG AGC TTC GTA GCG CAT GTC ATG GCC TTC GCT GCC TGT CTG GAG 2351 Gln Ser Phe Val Ala His Val Met Ala Phe Ala Ala Cys Leu Glu CCC TAC ACG GCC TGC CTC TAG 2372 Pro Tyr Thr Ala Cys Leu ***

Claims (8)

【特許請求の範囲】[Claims] 【請求項１】少なくとも下記３種類の遺伝子を独立して
発現し得る形態で含有する、組換えアルカリフォスファ
タ−ゼ融合抗体製造用の単一発現ベクタ−又は複数の発
現ベクタ−のセット。 第１の遺伝子；抗体のＨ鎖Ｖ及びＣＨ１領域、又はその
誘導体のアミノ酸配列をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にアルカリフォスファタ−ゼ又はその誘導体
のアミノ酸配列をコ−ドする遺伝子を含み、その発現に
より抗体のＨ鎖Ｖ及びＣＨ１領域、又はその誘導体とア
ルカリフォスファタ−ゼ又はその誘導体との融合タンパ
ク質か、あるいは、抗体のＬ鎖又はその誘導体とアルカ
リフォスファタ−ゼ又はその誘導体との融合タンパク質
を発現し得るものである）。1. A single expression vector or a set of a plurality of expression vectors for producing a recombinant alkaline phosphatase fusion antibody, which contains at least the following three kinds of genes in a form capable of being independently expressed. First gene; gene encoding the amino acid sequence of antibody H chain V and CH1 region or its derivative Second gene; gene encoding the amino acid sequence of antibody L chain or its derivative Third gene Gene; a gene encoding the amino acid sequence of alkaline phosphatase or a derivative thereof (either the first gene or the second gene is further downstream of the amino acid sequence of alkaline phosphatase or a derivative thereof). Or a fusion protein of an antibody H chain V and CH1 region or a derivative thereof with an alkaline phosphatase or a derivative thereof, or an antibody L chain or a derivative thereof with an alkali. It is capable of expressing a fusion protein with phosphatase or a derivative thereof). 【請求項２】少なくとも下記２種類の遺伝子を独立して
発現し得る形態で含有する、組換えアルカリフォスファ
タ−ゼ融合タンパク質製造用の単一発現ベクタ−又は複
数の発現ベクタ−のセット。 第１の遺伝子；任意のタンパク質又はその誘導体のアミ
ノ酸配列をコ−ドする遺伝子とその下流のアルカリフォ
スファタ−ゼ又はその誘導体のアミノ酸配列をコ−ドす
る遺伝子を含み、その発現により任意のタンパク質又は
その誘導体とアルカリフォスファタ−ゼ又はその誘導体
との融合タンパク質を発現し得る遺伝子 第２の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子2. A single expression vector or a set of a plurality of expression vectors for producing a recombinant alkaline phosphatase fusion protein, which contains at least the following two kinds of genes in a form capable of being independently expressed. First gene; including a gene encoding an amino acid sequence of an arbitrary protein or its derivative and a gene encoding an amino acid sequence of alkaline phosphatase or its derivative downstream thereof, an arbitrary protein depending on its expression Or a gene capable of expressing a fusion protein of its derivative with alkaline phosphatase or its derivative; second gene; a gene encoding the amino acid sequence of alkaline phosphatase or its derivative 【請求項３】少なくとも下記３種類の遺伝子を独立して
発現し得る、単一発現ベクタ−及び／又は複数の発現ベ
クタ−のセットで形質転換した宿主細胞を培養し、培養
物から前記遺伝子の発現物を取得することを特徴とする
組換えアルカリフォスファタ−ゼ融合抗体の製造方法。 第１の遺伝子；抗体のＨ鎖Ｖ及びＣＨ１領域、又はその
誘導体のアミノ酸配列をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にアルカリフォスファタ−ゼ又はその誘導体
のアミノ酸配列をコ−ドする遺伝子を含み、その発現に
より抗体のＨ鎖Ｖ及びＣＨ１領域、又はその誘導体とア
ルカリフォスファタ−ゼ又はその誘導体との融合タンパ
ク質か、あるいは、抗体のＬ鎖又はその誘導体とアルカ
リフォスファタ−ゼ又はその誘導体との融合タンパク質
を発現し得るものである）。3. A host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following three types of genes, and culturing the host cells of the gene from the culture. A method for producing a recombinant alkaline phosphatase fusion antibody, which comprises obtaining an expression product. First gene; gene encoding the amino acid sequence of antibody H chain V and CH1 region or its derivative Second gene; gene encoding the amino acid sequence of antibody L chain or its derivative Third gene Gene; a gene encoding the amino acid sequence of alkaline phosphatase or a derivative thereof (either the first gene or the second gene is further downstream of the amino acid sequence of alkaline phosphatase or a derivative thereof). Or a fusion protein of an antibody H chain V and CH1 region or a derivative thereof with an alkaline phosphatase or a derivative thereof, or an antibody L chain or a derivative thereof with an alkali. It is capable of expressing a fusion protein with phosphatase or a derivative thereof). 【請求項４】少なくとも下記２種類の遺伝子を独立して
発現し得る、単一発現ベクタ−及び／又は複数の発現ベ
クタ−のセットで形質転換した宿主細胞を培養し、培養
物から前記遺伝子の発現物を取得することを特徴とする
組換えアルカリフォスファタ−ゼ融合タンパク質の製造
方法。 第１の遺伝子；任意のタンパク質又はその誘導体のアミ
ノ酸配列をコ−ドする遺伝子とその下流のアルカリフォ
スファタ−ゼ又はその誘導体のアミノ酸配列をコ−ドす
る遺伝子を含み、その発現により任意のタンパク質又は
その誘導体とアルカリフォスファタ−ゼ又はその誘導体
との融合タンパク質を発現し得る遺伝子 第２の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子4. A host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following two kinds of genes, and culturing the host cell, and culturing the above gene from the culture. A method for producing a recombinant alkaline phosphatase fusion protein, which comprises obtaining an expression product. First gene; including a gene encoding an amino acid sequence of an arbitrary protein or its derivative and a gene encoding an amino acid sequence of alkaline phosphatase or its derivative downstream thereof, an arbitrary protein depending on its expression Or a gene capable of expressing a fusion protein of its derivative with alkaline phosphatase or its derivative; second gene; a gene encoding the amino acid sequence of alkaline phosphatase or its derivative 【請求項５】少なくとも下記３種類の遺伝子を独立して
発現し得る、単一発現ベクタ−及び／又は複数の発現ベ
クタ−のセットで形質転換した宿主細胞を培養して取得
される組換えアルカリフォスファタ−ゼ融合抗体を使用
する、免疫化学的測定方法。 第１の遺伝子；抗体のＨ鎖Ｖ及びＣＨ１領域、又はその
誘導体のアミノ酸配列をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にアルカリフォスファタ−ゼ又はその誘導体
のアミノ酸配列をコ−ドする遺伝子を含み、その発現に
より抗体のＨ鎖Ｖ及びＣＨ１領域、又はその誘導体とア
ルカリフォスファタ−ゼ又はその誘導体との融合タンパ
ク質か、あるいは、抗体のＬ鎖又はその誘導体とアルカ
リフォスファタ−ゼ又はその誘導体との融合タンパク質
を発現し得るものである）。5. A recombinant alkali obtained by culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following three kinds of genes. An immunochemical assay method using a phosphatase fusion antibody. First gene; gene encoding the amino acid sequence of antibody H chain V and CH1 region or its derivative Second gene; gene encoding the amino acid sequence of antibody L chain or its derivative Third gene Gene; a gene encoding the amino acid sequence of alkaline phosphatase or a derivative thereof (either the first gene or the second gene is further downstream of the amino acid sequence of alkaline phosphatase or a derivative thereof). Or a fusion protein of an antibody H chain V and CH1 region or a derivative thereof with an alkaline phosphatase or a derivative thereof, or an antibody L chain or a derivative thereof with an alkali. It is capable of expressing a fusion protein with phosphatase or a derivative thereof). 【請求項６】少なくとも下記２種類の遺伝子を独立して
発現し得る、単一発現ベクタ−及び／又は複数の発現ベ
クタ−のセットで形質転換した宿主細胞を培養して取得
される組換えアルカリフォスファタ−ゼ融合タンパク質
を使用する、免疫化学的測定方法。 第１の遺伝子；任意のタンパク質又はその誘導体のアミ
ノ酸配列をコ−ドする遺伝子とその下流のアルカリフォ
スファタ−ゼ又はその誘導体のアミノ酸配列をコ−ドす
る遺伝子を含み、その発現により任意のタンパク質又は
その誘導体とアルカリフォスファタ−ゼ又はその誘導体
との融合タンパク質を発現し得る遺伝子 第２の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子6. A recombinant alkali obtained by culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following two genes. An immunochemical assay method using a phosphatase fusion protein. First gene; including a gene encoding an amino acid sequence of an arbitrary protein or its derivative and a gene encoding an amino acid sequence of alkaline phosphatase or its derivative downstream thereof, an arbitrary protein depending on its expression Or a gene capable of expressing a fusion protein of its derivative with alkaline phosphatase or its derivative; second gene; a gene encoding the amino acid sequence of alkaline phosphatase or its derivative 【請求項７】少なくとも下記３種類の遺伝子を独立して
発現し得る、単一発現ベクタ−及び／又は複数の発現ベ
クタ−のセットで形質転換した宿主細胞を培養して取得
される組換えアルカリフォスファタ−ゼ融合抗体を含
む、免疫化学的測定用キット。 第１の遺伝子；抗体のＨ鎖Ｖ及びＣＨ１領域、又はその
誘導体のアミノ酸配列をコ−ドする遺伝子 第２の遺伝子；抗体のＬ鎖又はその誘導体のアミノ酸配
列をコ−ドする遺伝子 第３の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子 （第１の遺伝子又は第２の遺伝子のいずれか一方は、更
にその下流にアルカリフォスファタ−ゼ又はその誘導体
のアミノ酸配列をコ−ドする遺伝子を含み、その発現に
より抗体のＨ鎖Ｖ及びＣＨ１領域、又はその誘導体とア
ルカリフォスファタ−ゼ又はその誘導体との融合タンパ
ク質か、あるいは、抗体のＬ鎖又はその誘導体とアルカ
リフォスファタ−ゼ又はその誘導体との融合タンパク質
を発現し得るものである）。7. A recombinant alkali obtained by culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following three kinds of genes: An immunochemical assay kit containing a phosphatase fusion antibody. First gene; gene encoding the amino acid sequence of antibody H chain V and CH1 region or its derivative Second gene; gene encoding the amino acid sequence of antibody L chain or its derivative Third gene Gene; a gene encoding the amino acid sequence of alkaline phosphatase or a derivative thereof (either the first gene or the second gene is further downstream of the amino acid sequence of alkaline phosphatase or a derivative thereof). Or a fusion protein of an antibody H chain V and CH1 region or a derivative thereof with an alkaline phosphatase or a derivative thereof, or an antibody L chain or a derivative thereof with an alkali. It is capable of expressing a fusion protein with phosphatase or a derivative thereof). 【請求項８】少なくとも下記２種類の遺伝子を独立して
発現し得る、単一発現ベクタ−及び／又は複数の発現ベ
クタ−のセットで形質転換した宿主細胞を培養して取得
される組換えアルカリフォスファタ−ゼ融合タンパク質
を含む、免疫化学的測定用キット。 第１の遺伝子；任意のタンパク質又はその誘導体のアミ
ノ酸配列をコ−ドする遺伝子とその下流のアルカリフォ
スファタ−ゼ又はその誘導体のアミノ酸配列をコ−ドす
る遺伝子を含み、その発現により任意のタンパク質又は
その誘導体とアルカリフォスファタ−ゼ又はその誘導体
との融合タンパク質を発現し得る遺伝子 第２の遺伝子；アルカリフォスファタ−ゼ又はその誘導
体のアミノ酸配列をコ−ドする遺伝子8. A recombinant alkali obtained by culturing a host cell transformed with a single expression vector and / or a set of a plurality of expression vectors capable of independently expressing at least the following two kinds of genes. An immunochemical assay kit containing a phosphatase fusion protein. First gene; including a gene encoding an amino acid sequence of an arbitrary protein or its derivative and a gene encoding an amino acid sequence of alkaline phosphatase or its derivative downstream thereof, an arbitrary protein depending on its expression Or a gene capable of expressing a fusion protein of its derivative with alkaline phosphatase or its derivative; second gene; a gene encoding the amino acid sequence of alkaline phosphatase or its derivative