JP5780693B2 - 免疫原性組成物 - Google Patents
免疫原性組成物 Download PDFInfo
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- JP5780693B2 JP5780693B2 JP2008546433A JP2008546433A JP5780693B2 JP 5780693 B2 JP5780693 B2 JP 5780693B2 JP 2008546433 A JP2008546433 A JP 2008546433A JP 2008546433 A JP2008546433 A JP 2008546433A JP 5780693 B2 JP5780693 B2 JP 5780693B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/085—Staphylococcus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/70—Multivalent vaccine
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Description
(a)配列群2の任意の配列のアミノ酸配列に対して少なくとも85%の同一性、好ましくは少なくとも90%の同一性、より好ましくは少なくとも95%の同一性、最も好ましくは少なくとも97%、98%、若しくは99%の同一性又は厳密な同一性を有するアミノ酸配列を含む単離されたポリペプチド;
(b)配列群1の任意の配列に対して、配列群1の選択される配列の全長にわたって、少なくとも85%の同一性、好ましくは少なくとも90%の同一性、より好ましくは少なくとも95%の同一性、さらにより好ましくは少なくとも97%、98%、若しくは99%の同一性又は厳密な同一性を有するポリヌクレオチド配列を含む単離されたポリヌクレオチドによってコードされるポリペプチド;あるいは
(c)配列群2の任意の配列のアミノ酸配列に対して少なくとも85%の同一性、好ましくは少なくとも90%の同一性、より好ましくは少なくとも95%の同一性、さらにより好ましくは少なくとも97〜99%の同一性又は厳密な同一性を有するポリペプチドをコードするポリヌクレオチド配列を含む単離されたポリヌクレオチドによってコードされるポリペプチド
を提供する。
本発明は、上述した本発明のポリペプチドのいずれか1つをコードする任意のポリヌクレオチドを開示する。
(a)配列群1の任意の配列に対して、上記配列群1のポリヌクレオチド配列の全長にわたって少なくとも85%の同一性、好ましくは少なくとも90%の同一性、より好ましくは少なくとも95%の同一性、さらにより好ましくは少なくとも97%、98%、若しくは99%の同一性又は厳密な同一性を有するポリヌクレオチド配列、あるいは
(b)配列群2から選択される任意のアミノ酸配列に対して、上記配列群2のアミノ酸配列の全長にわたって少なくとも85%の同一性、好ましくは少なくとも90%の同一性、より好ましくは少なくとも95%の同一性、さらにより好ましくは少なくとも97%、98%、若しくは99%の同一性又は100%の厳密性を有するポリペプチドをコードするポリヌクレオチド配列
を含むか、又はそれからなる単離されたポリヌクレオチドを提供する。
本発明は、本発明の1又は複数のポリヌクレオチドを含むベクター、本発明のベクターで遺伝子改変された宿主細胞、及び組換え技法による本発明のポリペプチドの産生にも関する。かかるタンパク質を産生するのに、本発明のDNA構築物に由来するRNAを用いた無細胞翻訳系を利用することもできる。
本発明の免疫原性組成物は、場合により別の抗原と組み合わせてもよい。ブドウ球菌IgG結合タンパク質の中和によって、別の抗原に対して生起される免疫応答が改善されることがある。
5型
→4)-β-D-ManNAcA(3OAc)-(1→4)-α-L-FucNAc(1→3)-β-D-FucNAc-(1→
8型
→3)-β-D-ManNAcA(4OAc)-(1→3)-α-L-FucNAc(1→3)-β-D-FucNAc-(1→
5型
→4)-β-D-ManNAcA-(1→4)-α-L-FucNAc(3OAc)-(1→3)-β-D-FucNAc-(1→
8型
→3)-β-D-ManNAcA(4OAc)-(1→3)-α-L-FucNAc(1→3)-α-D-FucNAc(1→
・a群)以下からなる群より選択される、少なくとも1つのブドウ球菌細胞外成分結合タンパク質又はその断片:Ebh、エラスチン結合タンパク質(EbpS)、EFB(FIB)、ClfA、ClfB、SdrC、SdrG、FnbA、SsaA、SasA、Aap、AhpC、ペニシリン結合タンパク質4、IsaA/PisA;
・b群)以下からなる群より選択される、少なくとも1つのブドウ球菌輸送タンパク質又はその断片:IsdA、IsdB、IsdC、HarA;
・c群)以下からなる群より選択される、少なくとも1つのブドウ球菌毒性・トキシン調節因子又はその断片:αトキシン(Hla)、αトキシンH35R変異体、RAP。
本発明の別の態様は、本発明の免疫原性組成物及び薬学的に許容される担体を含むワクチンである。
65kDaのプロテインA−Sbi融合タンパク質は、プロテインA遺伝子の断片とSbi遺伝子の断片を融合し、発現ベクターTCMP14にクローニングし、融合タンパク質を大腸菌において発現させることにより作製した。
方法:
4週齢のCD1雌マウス25匹の群を、8μgのプロテインA(ProtA)又はProtA−SBI融合タンパク質(いずれもAlPO4アジュバントを添加)で3回(第0日、第14日、及び第28日)、筋内注射により免疫した。対照マウスには、等量のAlPO4アジュバント又は死滅全細胞黄色ブドウ球菌5血清型Reynolds(5 108CFU)(AlPO4アジュバントを添加)を免疫した。第42日に、5%のムチンを添加した500μlの黄色ブドウ球菌5 Reynolds株(3 106CFU)をマウスの腹腔内に投与してチャレンジした。チャレンジ後4日目までマウスの死亡を調べた。
結果を図4に示す。予想されたとおり、AlPO4単独で免疫したマウスでは防御が観察されなかった。同種の死滅全細胞で免疫した陽性対照群では非常に良好な防御が観察された。ProtAで免疫した後に防御は観察されなかった。ProtA−SBI構築物で免疫したマウスにおいては、統計学的に有意ではないが、高い生存率(24%)が観察された。
融合タンパク質におけるプロテインAとSbi IgGドメインの組み合わせの免疫によって、プロテインA単独での免疫よりも高い防御をもたらすことができる。このモデルにおけるプロテインA−Sbi融合タンパク質での免疫により誘導される黄色ブドウ球菌感染に対する防御は、有効な黄色ブドウ球菌ワクチンを得るためにこの抗原を他の候補と組み合わせて使用することができることを示唆している。
ClustalWプログラムを用いて黄色ブドウ球菌Col株、Mu50株、NCTC8325株、N315株、Mw2株、MRSA252株及びMSSA476株由来のSbi配列を比較し、同一性%を計算した。このアライメントを図5に示すが、配列は92〜100%の同一性を有することがわかった。
sdrGをProtA遺伝子とSbi遺伝子の間のBamHI部位に挿入することにより実施例1に記載のプロテインA−Sbi構築物にsdrG遺伝子をクローニングし、ProtA−SdrG−Sbi構築物を作製した。
配列番号1:Sbi ドメイン1
TQNNYVTDQQKAFYQVLHLKGITEEQRNQYIKTLREHPERAQEVFSESLKDS
KNPDRRVAQQNAFYNVLKNDNLTEQEKNNYIAQIKENPDRSQQVWVESVQSSKA
TQNNYVTDQQKAFYQVLHLKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKN
PDRRVAQQNAFYNVLKNDNLTEQEKNNYIAQIKENPDRSQQVWVESVQSSKA
SENTQQTSTKHQTTQNNYVTDQQKAFYQVLHLKGITEEQRNQYIKTLREHPERAQEVFSE
SLKDSKNPDRRVAQQNAFYNVLKNDNLTEQEKNNYIAQIKENPDRSQQVWVESVQSSKAK
ERQNIENADKAIKDFQDNKAPHDKSAAYEANSKLPKDLRDKNNRFVEKVSIEKA
MKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQVLH
LKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQE
KNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEAN
SKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNEKDSIENRRLAQREVNKA
PMDVKEHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKVESPKVEVPQIQSPKVE
VPQSKLLGYYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNTYYKYKGAIDQTVLTVL
GSGSKSYIQPLKVDDKNGYLAKSYAQVRNYVTESINTGKVLYTFYQNPTLVKTAIKAQET
ASSIKNTLSNLLSFWK
MHMKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQV
LHLKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTE
QEKNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYE
ANSKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNEKDSIENRRLAQREVN
KAPMDVKEHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKAESPKVEVPQSKLLG
YYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNTYYKYKGAIDQTVLTVLGSGSKSYI
QPLKVDDKNGYLAKSYAQVRNYVTESINTGKVLYTFYQNPTLVKTAIKAQETASSIKNTL
SNLLSFWK
MKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQVLH
LKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQE
KNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEAN
SKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNEKDSIENRRLAQREVNKA
PMDVQKHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKAESPKVEVPQIQSPKVE
VPQSKLLGYYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNKYYQYKGLIDKTVLTTI
GSGYGSYIKPLEVSKESGNLAKSYAQVRNYVTESINTGKVLYAFYQKPELVKTAIKAQET
ATTFKNALTGIFKSFWK
MKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQVLH
LKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQE
KNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEAN
SKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNVKDSIENRRLAQREVNKA
PMDVKEHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKAESPKVEVPQIQSPKVE
VPQSKLLGYYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNTYYKYKGAIDKAVLTLL
GDGSKSYIQPLKVDDKNGYLAKSYAQVRNYVTESINTGKVLYTFYQNPTLVKTAIKAQET
ASSIKNTITGLFNSFWK
MKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQVLH
LKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQE
KNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEAN
SKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNVKDSIENRRLAQREVNKA
PMDVKEHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKAESPKVEVPQIQSPKVE
VPQSKLLGYYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNTYYKYKGAIDKAVLTLL
GDGSKSYIQPLKVDDKNGYLAKSYAQVRNYVTESINTGKVLYTFYQNPTLVKTAIKAQET
ASSIKNTITGLFNSFWK
MKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQVLH
LKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQE
KNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEAN
SKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNEKDSIENRRLAQREVNKA
PMDVKEHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKAESPKVEVPQIQSPKVE
VPQSKLLGYYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNTYYKYKGAIDQTVLTVL
GSGSKSYIQPLKVDDKNGYLAKSYAQVRNYVTESINTGKVLYTFYQNPTLVKTAIKAQET
ASSIKNTLSNLLSFWK
MKNKYISKLLVGAATITLATMISNGEAKASENTQQTSTKHQTTQNNYVTDQQKAFYQVLH
LKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQE
KNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEAN
SKLPKDLRDKNNRFVEKVSIEKAIVRHDERVKSANDAISKLNEKDSIENRRLAQREVNKA
PMDVKEHLQKQLDALVAQKDAEKKVAPKVEAPQIQSPQIEKPKVESPKVEVPQIQSPKVE
VPQSKLLGYYQSLKDSFNYGYKYLTDTYKSYKEKYDTAKYYYNTYYKYKGAIDQTVLTVL
GSGSKSYIQPLKVDDKNGYLAKSYAQVRNYVTESINTGKVLYTFYQNPTLVKTAIKAQET
ASSIKNTLSNLLSFWK
NAAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDS
配列番号13:SPA ドメイン2 (V8)
QQNKFNKDQQSAFYEILNMPNLNEEQRNGFIQSLKDDPSQSTNVLGEAKKLNES
配列番号14:ドメイン2 (Mu50)
QQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEAKKLNES
ADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNES
配列番号16:ドメイン3 (V8)
ADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDA
配列番号17:ドメイン3 (MU50)
ADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANLLSEAKKLNES
ADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDA
配列番号19:ドメイン4 (V8)
ADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDA
配列番号20:ドメイン4 (MU50)
ADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSVSKEILAEAKKLNDA
ADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDA
MAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQ
APKADAQQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNES
QQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNES
ADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDA
ADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKD
DPSVSKEILAEAKKLNDAQA
MAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQ
APKADAQQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNES
QQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDA
QAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKD
DPSVSKEILAEAKKLNDAQA
AQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQ
APKADAQQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDA
QQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKD
DPSVSKEILAEAKKLNDAQA
AQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQ
APKADAQQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKD
DPSVSKEILAEAKKLNDAQA
MAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQ
APKADAQQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEA
KKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANL
LSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQ
SANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFIQSLKD
DPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKEDNNKPGKEDNNKPG
KEDNNKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDGNK
PGKEDGNGVHVG
MKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEA
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFI
QSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKEDNNKPGKEDNNKPGK
EDNNKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDGNKPGKEDGN
GVHVVKPGDTVNDIAKANGTTADKIAADNKLADKNMIKPGQELVVDKKQPANHADANKAQ
ALPETGEENPFIGTTVFGGLSLALGAALLAGRRREL
MKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEA
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNKKPGKEDGNKPGKEDGNKPGKEDNKKP
GKEDGNKPGKEDNNKPGKEDGNKPGKEDNNKPGKEDGNKPGKEDGNKPGKEDGNGVHVVK
PGDTVNDIAKANGTTADKIAADNKLADKNMIKPGQELVVDKKQPANHADANKAQALPETG
EENPFIGTTVFGGLSLALGAALLAGRRREL
MKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEA
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNKKPGKEDGNKPGKEDGNKPGKEDNKKP
GKEDGNKPGKEDNNKPGKEDGNKPGKEDNNKPGKEDGNKPGKEDGNKPGKEDGNGVHVVK
PGDTVNDIAKANGTTADKIAADNKLADKNMIKPGQELVVDKKQPANHADANKAQALPETG
EENPFIGTTVFGGLSLALGAALLAGRRREL
MKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEA
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFI
QSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDGNKPGKEDGNKPGKEDNNKPGK
EDGNKPGKEDNKKPGKEDGNKPGKEDNNKPGKEDGNGVHVVKPGDTVNDIAKANGTTADK
IAADNKLADKNMIKPGQELVVDKKQPANHADANKAQALPETGEENPFIGTTVFGGLSLAL
GAALLAGRRREL
LKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEA
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFI
QSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKEDNNKPGKEDNNKPGK
EDGNKPGKEDNKKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDGNKPGKEDGNGVHVVKPG
DTVNDIAKANGTTADKIAADNKLADKNMIKPGQELVVDKKQPANHADANKAQALPETGEE
NPFIGTTVFGGLSLALGAALLAGRRREL
LKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNKFNKDQQSAFYEILNMPNLNEE
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLAEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFI
QSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKEDGNKPGKEDNKKPGK
EDGNKPGKEDNKKPGKEDGNKPGKEDGNKPGKEDGNKPGKEDGNKPGKEDGNKPGKEDGN
GVHVVKPGDTVNDIAKANGTTADKIAADNKLADKNMIKPGQELVVDKKQPANHADANKAQ
ALPETGEENPFIGTTVFGGLSLALGAALLAGRRREL
LKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFYQVLNMPNLNADQ
RNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMPNLNEA
QRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQR
NGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNG
FIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEILHLPNLTEEQRNGFI
QSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDGNKPGKEDGNKPGKEDNNKPGK
EDGNKPGKEDNKKPGKEDGNKPGKEDNNKPGKEDGNGVHVVKPGDTVNDIAKANGTTADK
IAADNKLADKNMIKPGQELVVDKKQPANHADANKAQALPETGEENPFIGTTVFGGLSLAL
GAALLAGRRREL
MMTLQIHTGGINLKKKNIYSIRKLGVGIASVTLGTLLISGGVTPAANAAQHDEAQQNAFY
QVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNKFNKDQQSAF
YEILNMPNLNEEQRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYE
ILNMPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFNKEQQNAFYEIL
HLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKED
GNKPGKEDNKKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDGNKPGKEDGNKPGKEDGNGV
HVVKPGDTVNDIAKANGTTADKIAVDNKLADKNMIKPGQELVVDKKQPANHADANKAQAL
PETGEENPFIGTTVFGGLSLALGAALLAGRRREL
MAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADA
QQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKAD
NNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNK
FNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFN
KEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPG
KEDNNKPGKEDNNKPGKEDNNKPGKEDNNKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDN
KKPGKEDGNKPGKEDGNKPGKEDGNGVHVGGSSENTQQTSTKHQTTQNNYVTDQQKAFYQ
VLHLKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLT
EQEKNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAY
EANSKLPKDLRDKNNRFVEKVSIEKA
MAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADA
QQNNFNKDQQSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKAD
NNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSANLLSEAKKLNESQAPKADNK
FNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFN
KEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPG
KEDNNKPGKEDNNKPGKEDNNKPGKEDNNKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDN
KKPGKEDGNKPGKEDGNKPGKEDGNGVHVGGSSENTQQTSTKHQTTQNNYVTDQQKAFYQ
VLHLKGITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLT
EQEKNNYIAQIKENPDRSQQVWVESVQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAY
EANSKLPKDLRDKNNRFVEKVSIEKATSGHHHHHH
ACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACATCTAAAAG
GTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCAGAACGTGC
ACAAGAAGTATTCTCTGAATCACTTAAAGACAGC
配列番号44:Sbiドメイン2
AAGAACCCAGACCGACGTGTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATA
ACTTAACTGAACAAGAAAAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAG
CCAACAAGTTTGGGTAGAATCAGTACAATCTTCTAAAGCT
ACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACATCTAAAAG
GTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCAGAACGTGC
ACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGTGTTGCACAA
CAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAAAAAAATAATT
ACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTAGAATCAGTACA
ATCTTCTAAAGCT
AGTGAAAACACGCAACAAACTTCAACTAAGCACCAAACAACTCAAAACAACTACGTAACAG
ATCAACAAAAAGCTTTTTATCAAGTATTACATCTAAAAGGTATCACAGAAGAACAACGTAA
CCAATACATCAAAACATTACGCGAACACCCAGAACGTGCACAAGAAGTATTCTCTGAATCA
CTTAAAGACAGCAAGAACCCAGACCGACGTGTTGCACAACAAAACGCTTTTTACAATGTTC
TTAAAAATGATAACTTAACTGAACAAGAAAAAAATAATTACATTGCACAAATTAAAGAAAA
CCCTGATAGAAGCCAACAAGTTTGGGTAGAATCAGTACAATCTTCTAAAGCTAAAGAACGT
CAAAATATTGAAAATGCGGATAAAGCAATTAAAGATTTCCAAGATAACAAAGCACCACACG
ATAAATCAGCAGCATATGAAGCTAACTCAAAATTACCTAAAGATTTACGTGATAAAAACAA
CCGCTTTGTAGAAAAAGTTTCAATTGAAAAAGCA
ATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACGTTAGCTACA
ATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACTAAGCAC
CAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACAT
CTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCA
GAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGT
GTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAA
AAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTA
GAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCA
ATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAAGCTAAC
TCAAAATTACCTAAAGATTTACGTGATAAAAACAACCGCTTTGTAGAAAAAGTTTCAATT
GAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATCTCAAAA
TTAAATGAAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAACAAAGCA
CCTATGGATGTAAAAGAGCATTTACAGAAACAATTAGACGCATTAGTTGCTCAAAAAGAT
GCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAAATTGAA
AAACCTAAAGTAGAATCACCAAAAGTTGAAGTCCCTCAAATTCAATCACCAAAAGTTGAG
GTTCCTCAATCTAAATTATTAGGTTACTACCAATCATTAAAAGATTCATTTAACTATGGT
TACAAGTATTTAACAGATACTTATAAAAGCTATAAAGAAAAATATGATACAGCAAAGTAC
TACTATAATACGTACTATAAATACAAAGGTGCGATTGATCAAACAGTATTAACAGTACTA
GGTAGTGGTTCTAAATCTTACATCCAACCATTGAAAGTTGATGATAAAAACGGCTACTTA
GCTAAATCATATGCACAAGTAAGAAACTATGTAACTGAGTCAATCAATACTGGTAAAGTA
TTATATACTTTCTACCAAAACCCAACATTAGTAAAAACAGCTATTAAAGCTCAAGAAACT
GCATCATCAATCAAAAATACATTAAGTAATTTATTATCATTCTGGAAATAA
ATACACATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACTTTA
GCTACAATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACT
AAGCACCAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTA
TTACATCTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAA
CACCCAGAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGAC
CGACGTGTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAA
CAAGAAAAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTT
TGGGTAGAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGAT
AAAGCAATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAA
GCTAACTCAAAATTACCTAAAGATTTACGCGATAAAAATAACCGCTTTGTAGAAAAAGTT
TCAATTGAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATC
TCAAAATTAAATGAAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAAC
AAAGCACCTATGGATGTAAAAGAGCATTTACAGAAACAATTAGACGCATTAGTAGCTCAA
AAAGATGCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAA
ATTGAAAAACCTAAAGCAGAATCACCAAAAGTTGAAGTCCCTCAATCTAAATTATTAGGT
TACTACCAATCATTAAAAGATTCATTTAACTATGGTTACAAGTATTTAACAGATACTTAT
AAAAGCTATAAAGAAAAATATGATACAGCAAAGTACTACTATAATACGTACTATAAATAC
AAAGGTGCGATTGATCAAACAGTATTAACAGTACTAGGTAGTGGTTCTAAATCTTACATC
CAACCATTGAAAGTTGATGATAAAAACGGCTACTTAGCTAAATCATATGCACAAGTAAGA
AACTATGTAACTGAGTCAATCAATACTGGTAAAGTATTATATACTTTCTACCAAAACCCA
ACATTAGTAAAAACAGCTATTAAAGCTCAAGAAACTGCATCATCAATCAAAAATACATTA
AGTAATTTATTATCATTCTGGAAATAA
ATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACTTTAGCTACA
ATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACTAAGCAC
CAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACAT
CTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCA
GAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGT
GTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAA
AAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTA
GAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCA
ATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAAGCTAAC
TCAAAATTACCTAAAGATTTACGTGATAAAAATAACCGCTTTGTAGAAAAAGTTTCAATT
GAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATCTCAAAA
TTAAATGAAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAATAAAGCA
CCTATGGATGTACAAAAGCATTTACAGAAACAATTAGACGCATTAGTAGCTCAAAAAGAT
GCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAAATTGAA
AAACCTAAAGCAGAATCACCAAAAGTTGAAGTCCCTCAAATTCAATCACCAAAAGTTGAG
GTTCCTCAATCTAAATTATTAGGTTACTACCAATCATTAAAAGATTCATTTAACTATGGT
TACAAGTATTTAACAGATACTTATAAAAGCTATAAAGAAAAATATGATACAGCAAAGTAC
TACTATAATAAATATTACCAATATAAAGGTTTGATTGATAAAACAGTTTTAACAACTATC
GGTAGTGGCTATGGTTCATACATTAAACCTCTTGAAGTAAGCAAAGAAAGCGGGAACTTA
GCTAAATCATATGCACAAGTAAGAAACTATGTAACTGAGTCAATCAACACTGGTAAAGTG
TTATACGCATTCTACCAAAAACCAGAATTAGTAAAAACAGCTATTAAAGCTCAAGAAACA
GCAACAACTTTCAAAAACGCTTTAACAGGCATATTCAAATCATTCTGGAAATAA
ATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACTTTAGCTACA
ATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACTAAGCAC
CAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACAT
CTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCA
GAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGT
GTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAA
AAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTA
GAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCA
ATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAAGCTAAC
TCAAAATTACCTAAAGATTTACGTGATAAAAATAACCGCTTTGTAGAAAAAGTTTCAATT
GAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATCTCAAAA
TTAAATGTAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAACAAAGCA
CCTATGGATGTAAAAGAGCATTTACAGAAACAATTAGACGCATTAGTAGCTCAAAAAGAT
GCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAAATTGAA
AAACCTAAAGCAGAATCACCAAAAGTTGAAGTCCCTCAAATCCAATCACCAAAAGTTGAG
GTTCCTCAATCTAAATTATTAGGTTACTACCAATCATTAAAAGATTCATTTAACTATGGT
TACAAGTATTTAACAGATACTTATAAAAGCTATAAAGAAAAATATGATACAGCAAAGTAC
TACTATAATACGTACTATAAATACAAAGGTGCGATTGACAAAGCTGTATTAACTTTACTT
GGCGATGGTTCTAAATCTTATATCCAACCATTGAAAGTTGATGATAAAAATGGCTATTTA
GCTAAATCATATGCACAAGTAAGAAACTATGTAACTGAGTCAATCAATACTGGTAAAGTA
TTATATACTTTCTACCAAAACCCAACATTAGTAAAAACAGCTATTAAAGCTCAAGAAACT
GCATCATCAATCAAAAATACAATAACTGGATTATTTAACTCATTCTGGAAATAA
ATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACTTTAGCTACA
ATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACTAAGCAC
CAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACAT
CTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCA
GAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGT
GTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAA
AAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTA
GAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCA
ATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAAGCTAAC
TCAAAATTACCTAAAGATTTACGTGATAAAAATAACCGCTTTGTAGAAAAAGTTTCAATT
GAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATCTCAAAA
TTAAATGTAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAACAAAGCA
CCTATGGATGTAAAAGAGCATTTACAGAAACAATTAGACGCATTAGTAGCTCAAAAAGAT
GCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAAATTGAA
AAACCTAAAGCAGAATCACCAAAAGTTGAAGTCCCTCAAATCCAATCACCAAAAGTTGAG
GTTCCTCAATCTAAATTATTAGGTTACTACCAATCATTAAAAGATTCATTTAACTATGGT
TACAAGTATTTAACAGATACTTATAAAAGCTATAAAGAAAAATATGATACAGCAAAGTAC
TACTATAATACGTACTATAAATACAAAGGTGCGATTGACAAAGCTGTATTAACTTTACTT
GGCGATGGTTCTAAATCTTATATCCAACCATTGAAAGTTGATGATAAAAATGGCTATTTA
GCTAAATCATATGCACAAGTAAGAAACTATGTAACTGAGTCAATCAATACTGGTAAAGTA
TTATATACTTTCTACCAAAACCCAACATTAGTAAAAACAGCTATTAAAGCTCAAGAAACT
GCATCATCAATCAAAAATACAATAACTGGATTATTTAACTCATTCTGGAAATAA
ATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACTTTAGCTACA
ATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACTAAGCAC
CAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACAT
CTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCA
GAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGT
GTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAA
AAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTA
GAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCA
ATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAAGCTAAC
TCAAAATTACCTAAAGATTTACGCGATAAAAATAACCGCTTTGTAGAAAAAGTTTCAATT
GAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATCTCAAAA
TTAAATGAAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAACAAAGCA
CCTATGGATGTAAAAGAGCATTTACAGAAACAATTAGACGCATTAGTAGCTCAAAAAGAT
GCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAAATTGAA
AAACCTAAAGCAGAATCACCAAAAGTTGAAGTCCCTCAAATCCAATCACCAAAAGTTGAG
GTTCCTCAATCTAAATTATTAGGTTACTACCAATCATTAAAAGATTCATTTAACTATGGT
TACAAGTATTTAACAGATACTTATAAAAGCTATAAAGAAAAATATGATACAGCAAAGTAC
TACTATAATACGTACTATAAATACAAAGGTGCGATTGATCAAACAGTATTAACAGTACTA
GGTAGTGGTTCTAAATCTTACATCCAACCATTGAAAGTTGATGATAAAAACGGCTACTTA
GCTAAATCATATGCACAAGTAAGAAACTATGTAACTGAGTCAATCAATACTGGTAAAGTA
TTATATACTTTCTACCAAAACCCAACATTAGTAAAAACAGCTATTAAAGCTCAAGAAACT
GCATCATCAATCAAAAATACATTAAGTAATTTATTATCATTCTGGAAATAA
ATGAAAAATAAATATATCTCGAAGTTGCTAGTTGGGGCAGCAACAATTACGTTAGCTACA
ATGATTTCAAATGGGGAAGCAAAAGCGAGTGAAAACACGCAACAAACTTCAACTAAGCAC
CAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACAT
CTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCA
GAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCAGACCGACGT
GTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACTGAACAAGAA
AAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTA
GAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCA
ATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATATGAAGCTAAC
TCAAAATTACCTAAAGATTTACGTGATAAAAACAACCGCTTTGTAGAAAAAGTTTCAATT
GAAAAAGCAATCGTTCGTCATGATGAGCGTGTGAAATCAGCAAATGATGCAATCTCAAAA
TTAAATGAAAAAGATTCAATTGAAAACAGACGTTTAGCACAACGTGAAGTTAACAAAGCA
CCTATGGATGTAAAAGAGCATTTACAGAAACAATTAGACGCATTAGTTGCTCAAAAAGAT
GCTGAAAAGAAAGTGGCGCCAAAAGTTGAGGCTCCTCAAATTCAATCACCACAAATTGAA
AAACCTAAAGTAGAATCACCAAAAGTTGAAGTCCCTCAAATTCAATCACCAAAAGTTGAG
GTTCCTCAATCTAAATTATTAGGTTACTACCAATCATTAAAAGATTCATTTAACTATGGT
TACAAGTATTTAACAGATACTTATAAAAGCTATAAAGAAAAATATGATACAGCAAAGTAC
TACTATAATACGTACTATAAATACAAAGGTGCGATTGATCAAACAGTATTAACAGTACTA
GGTAGTGGTTCTAAATCTTACATCCAACCATTGAAAGTTGATGATAAAAACGGCTACTTA
GCTAAATCATATGCACAAGTAAGAAACTATGTAACTGAGTCAATCAATACTGGTAAAGTA
TTATATACTTTCTACCAAAACCCAACATTAGTAAAAACAGCTATTAAAGCTCAAGAAACT
GCATCATCAATCAAAAATACATTAAGTAATTTATTATCATTCTGGAAATAA
AATGCTGCGCAACACGATGAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCT
AACTTAAATGCTGATCAACGCAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAA
AGTGCTAACGTTTTAGGTGAAGCTCAAAAACTTAATGACTCT
配列番号55:SPAドメイン2 (V8)
CAACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGA
GCAACGCAATGGTTTCATTCAAAGTCTTAAAGACGATCCAAGCCAAAGCACTAACGTTTT
AGGTGAAGCTAAAAAATTAAACGAATCT
配列番号56:ドメイン2 (Mu50)
CAACAAAATAACTTCAACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCT
AACTTAAACGAAGCGCAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAA
AGCACTAATGTTTTAGGTGAAGCTAAAAAATTAAACGAATCT
GCTGACAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCT
AACTTGAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAA
AGTGCTAACCTTTTAGCAGAAGCTAAAAAGTTAAATGAATCT
配列番号58:ドメイン3 (V8)
GCTGACAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCT
AACTTGAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAA
AGTGCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCA
配列番号59:ドメイン3 (MU50)
GCTGATAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCT
AACTTAAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAA
AGTGCTAACCTATTGTCAGAAGCTAAAAAGTTAAATGAATCT
GCTGATAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCT
AACTTAAATGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAA
AGCGCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCA
配列番号61:ドメイン4 (V8)
GCTGACAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCT
AACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCTTCAGTG
AGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTAAACGATGCT
配列番号62:ドメイン4 (MU50)
GCGGATAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCT
AACTTAAACGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCTTCAGTG
AGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTAAACGATGCT
GCTGACAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCT
AACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCTTCAGTG
AGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTAAACGATGCT
ATGGCGCAACACGATGAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCTAAC
TTAAATGCTGATCAACGCAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGT
GCTAACGTTTTAGGTGAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCG
CAACAAAATAACTTCAACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCT
AACTTAAACGAAGCGCAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAA
AGCACTAACGTTTTAGGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGAT
AACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTA
AACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCT
AACCTATTGTCAGAAGCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAA
TTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAA
GAACAACGCAATGGTTTCATCCAAAGCCTAAAAGATGACCCAAGCCAAAGCGCTAACCTT
TTAGCAGAAGCTAAAAAGCTAAATGATGCTCAAGCACCAAAAGCTGACAACAAATTCAAC
AAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAA
CGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCA
GAAGCTAAAAAGCTAAACGATGCTCAAGCACCAAAAGAGGAAGACAATAACAAGCCTGGC
AAAGAAGACAATAACAAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGACAAC
AACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGCAAAGAAGACGGCAACAAGCCTGGT
AAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACAAC
AAAAAACCTGGTAAAGAAGACGGCAACAAGCCTGGCAAAGAAGATGGCAACAAACCTGGT
AAAGAAGATGGTAACGGAGTACATGTCGGC
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCTAACTTAAATGCTGATCAA
CGCAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAACTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGCG
CAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAAAGCACTAACGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGATAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTAAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCTAACCTATTGTCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGCAATGGT
TTCATCCAAAGCCTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAA
AAGCTAAATGATGCTCAAGCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAAT
GCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATC
CAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTA
AACGATGCTCAAGCACCAAAAGAGGAAGACAATAACAAGCCTGGCAAAGAAGACAATAAC
AAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGTAAA
GAAGACAACAACAAGCCTGGCAAAGAAGACGGCAACAAGCCTGGTAAAGAAGACAACAAA
AAACCTGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACAACAAAAAACCTGGTAAA
GAAGACGGCAACAAGCCTGGCAAAGAAGATGGCAACAAACCTGGTAAAGAAGATGGTAAC
GGAGTACATGTCGTTAAACCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACT
ACTGCTGACAAAATTGCTGCAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGT
CAAGAACTTGTTGTTGATAAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAA
GCATTACCAGAAACTGGTGAAGAAAATCCATTCATCGGTACAACTGTATTTGGTGGATTA
TCATTAGCCTTAGGTGCAGCGTTATTAGCTGGACGTCGTCGCGAACTATAA
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTGTTAAATATGCCTAACTTAAACGCTGATCAA
CGTAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAACTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGCG
CAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAAAGCACTAATGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGATAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTAAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCTAACCTATTGTCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGTAACGGC
TTCATCCAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAA
AAGCTAAACGATGCTCAAGCACCAAAAGAGGAAGACAACAAAAAACCTGGTAAAGAAGAC
GGCAACAAACCTGGCAAAGAAGACGGCAACAAGCCTGGTAAAGAAGACAACAAAAAACCT
GGTAAAGAAGACGGCAACAAGCCTGGTAAAGAAGACAACAACAAACCTGGCAAAGAAGAC
GGCAACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGTAAAGAAGACGGCAACAAGCCT
GGTAAAGAAGACGGCAACAAACCTGGTAAAGAAGACGGCAACGGAGTACATGTCGTTAAA
CCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACTACTGCTGACAAAATTGCT
GCAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGTCAAGAACTTGTTGTTGAT
AAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAAGCATTACCAGAAACTGGT
GAAGAAAATCCATTCATCGGTACAACTGTATTTGGTGGATTATCATTAGCCTTAGGTGCA
GCGTTATTAGCTGGACGTCGTCGCGAACTATAA
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTGTTAAATATGCCTAACTTAAACGCTGATCAA
CGTAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAACTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGCG
CAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAAAGCACTAATGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGATAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTAAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCTAACCTATTGTCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGTAACGGC
TTCATCCAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAA
AAGCTAAACGATGCTCAAGCACCAAAAGAGGAAGACAACAAAAAACCTGGTAAAGAAGAC
GGCAACAAACCTGGCAAAGAAGACGGCAACAAGCCTGGTAAAGAAGACAACAAAAAACCT
GGTAAAGAAGACGGCAACAAGCCTGGTAAAGAAGACAACAACAAACCTGGCAAAGAAGAC
GGCAACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGTAAAGAAGACGGCAACAAGCCT
GGTAAAGAAGACGGCAACAAACCTGGTAAAGAAGACGGCAACGGAGTACATGTCGTTAAA
CCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACTACTGCTGACAAAATTGCT
GCAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGTCAAGAACTTGTTGTTGAT
AAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAAGCATTACCAGAAACTGGT
GAAGAAAATCCATTCATCGGTACAACTGTATTTGGTGGATTATCATTAGCCTTAGGTGCA
GCGTTATTAGCTGGACGTCGTCGCGAACTATAA
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTGTTAAATATGCCTAACTTAAACGCTGATCAA
CGTAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAACTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGCG
CAACGCAATGGTTTCATTCAAAGTCTTAAAGACGATCCAAGCCAAAGCACTAACGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGACAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCTAACTTGAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAAAGTGCTAACCTATTGTCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGCAATGGT
TTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAA
AAGCTAAATGATGCACAAGCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAAT
GCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATC
CAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTA
AACGATGCTCAAGCACCAAAAGAGGAAGACAACAACAAACCTGGTAAAGAAGACGGCAAC
AAACCTGGCAAAGAAGACGGCAACAAACCTGGCAAAGAAGACAACAACAAGCCTGGCAAA
GAAGACGGCAACAAACCTGGTAAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAAC
AAGCCTGGCAAAGAAGACAACAACAAACCTGGTAAAGAAGACGGCAACGGAGTACATGTC
GTTAAACCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACTACTGCTGACAAA
ATTGCTGCAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGTCAAGAACTTGTT
GTTGATAAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAAGCATTACCAGAA
ACTGGTGAAGAAAATCCATTCATTGGTACAACTGTATTTGGTGGATTATCATTAGCGTTA
GGTGCAGCGTTATTAGCTGGACGTCGTCGCGAACTATAA
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCTAACTTAAATGCTGATCAA
CGCAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAACTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGCG
CAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAAAGCACTAACGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGATAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTAAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCTAACCTATTGTCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGCAATGGT
TTCATCCAAAGCCTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAA
AAGCTAAATGATGCTCAAGCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAAT
GCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATC
CAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTA
AACGATGCTCAAGCACCAAAAGAGGAAGACAATAACAAGCCTGGCAAAGAAGACAATAAC
AAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGCAAA
GAAGACGGCAACAAGCCTGGTAAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAAC
AAGCCTGGTAAAGAAGACAACAAAAAACCTGGTAAAGAAGACGGCAACAAGCCTGGCAAA
GAAGATGGCAACAAACCTGGTAAAGAAGATGGTAACGGAGTACATGTCGTTAAACCTGGT
GATACAGTAAATGACATTGCAAAAGCAAACGGCACTACTGCTGACAAAATTGCTGCAGAT
AACAAATTAGCTGATAAAAACATGATCAAACCTGGTCAAGAACTTGTTGTTGATAAGAAG
CAACCAGCAAACCATGCAGATGCTAACAAAGCTCAAGCATTACCAGAAACTGGTGAAGAA
AATCCATTCATCGGTACAACTGTATTTGGTGGATTATCATTAGCCTTAGGTGCAGCGTTA
TTAGCTGGACGTCGTCGCGAACTATAA
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTGTTAAATATGCCTAACTTAAACGCTGATCAA
CGTAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAAGTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGAG
CAACGCAATGGTTTCATTCAAAGTCTTAAAGACGATCCAAGCCAAAGCACTAACGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGACAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCTAACTTGAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAAAGTGCTAACCTTTTAGCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCTGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAATGAAGAACAACGCAATGGT
TTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAA
AAGCTAAATGATGCACAAGCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAAT
GCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATC
CAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTA
AACGATGCTCAAGCACCAAAAGAGGAAGACAACAACAAGCCTGGCAAAGAAGACAACAAC
AAGCCTGGTAAAGAAGACGGCAACAAACCTGGTAAAGAAGACAACAAAAAACCTGGCAAA
GAAGACGGCAACAAACCTGGTAAAGAAGACAACAAAAAACCTGGCAAAGAAGATGGCAAC
AAACCTGGTAAAGAAGACGGCAACAAGCCTGGTAAAGAAGATGGCAACAAGCCTGGTAAA
GAAGATGGCAACAAGCCTGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACGGCAAC
GGAGTACATGTCGTTAAACCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACT
ACTGCTGACAAAATTGCTGCAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGT
CAAGAACTTGTTGTTGATAAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAA
GCATTACCAGAAACTGGTGAAGAAAATCCATTCATCGGTACAACTGTATTTGGTGGATTA
TCATTAGCGTTAGGTGCAGCGTTATTAGCTGGACGTCGTCGCGAACTATAA
TTGAAAAAGAAAAACATTTATTCAATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACT
TTAGGTACATTACTTATATCTGGTGGCGTAACACCTGCTGCAAATGCTGCGCAACACGAT
GAAGCTCAACAAAATGCTTTTTATCAAGTGTTAAATATGCCTAACTTAAACGCTGATCAA
CGTAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGT
GAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCGCAACAAAATAACTTC
AACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCTAACTTAAACGAAGCG
CAACGCAATGGTTTCATTCAAAGTCTTAAAGACGATCCAAGCCAAAGCACTAACGTTTTA
GGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGACAACAATTTCAACAAA
GAACAACAAAATGCTTTCTATGAAATCTTGAACATGCCTAACTTGAACGAAGAACAACGC
AATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGTCAAAGTGCTAACCTATTGTCAGAA
GCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAA
CAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGCAATGGT
TTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAA
AAGCTAAATGATGCACAAGCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAAT
GCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATC
CAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTA
AACGATGCTCAAGCACCAAAAGAGGAAGACAACAACAAACCTGGTAAAGAAGACGGCAAC
AAACCTGGTAAAGAAGACGGCAACAAACCTGGCAAAGAAGACAACAACAAGCCTGGCAAA
GAAGACGGCAACAAACCTGGTAAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAAC
AAGCCTGGCAAAGAAGACAACAACAAACCTGGTAAAGAAGACGGCAACGGAGTACATGTC
GTTAAACCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACTACTGCTGACAAA
ATTGCTGCAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGTCAAGAACTTGTT
GTTGATAAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAAGCATTACCAGAA
ACTGGTGAAGAAAATCCATTCATTGGTACAACTGTATTTGGTGGATTATCATTAGCGTTA
GGTGCAGCGTTATTAGCTGGACGTCGTCGCGAACTATAA
ATGATGACTTTACAAATACATACAGGGGGTATTAATTTGAAAAAGAAAAACATTTATTCA
ATTCGTAAACTAGGTGTAGGTATTGCATCTGTAACTTTAGGTACATTACTTATATCTGGT
GGCGTAACACCTGCTGCAAATGCTGCGCAACACGATGAAGCTCAACAAAATGCTTTTTAT
CAAGTGTTAAATATGCCTAACTTAAACGCTGATCAACGTAATGGTTTTATCCAAAGCCTT
AAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGTGAAGCTCAAAAACTTAATGACTCT
CAAGCTCCAAAAGCTGATGCGCAACAAAATAAGTTCAACAAAGATCAACAAAGCGCCTTC
TATGAAATCTTGAACATGCCTAACTTAAACGAAGAGCAACGCAATGGTTTCATTCAAAGT
CTTAAAGACGATCCAAGCCAAAGCACTAACGTTTTAGGTGAAGCTAAAAAATTAAACGAA
TCTCAAGCACCGAAAGCTGACAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAA
ATCTTGAACATGCCTAACTTGAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAA
GATGACCCAAGTCAAAGTGCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCACAA
GCACCAAAAGCTGACAACAAATTCAACAAAGAACAACAAAATGCTTTCTATGAAATTTTA
CATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAGCCTTAAAGACGAT
CCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTAAACGATGCTCAAGCACCA
AAAGAGGAAGACAACAACAAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGAC
GGCAACAAACCTGGTAAAGAAGACAACAAAAAACCTGGCAAAGAAGACGGCAACAAACCT
GGTAAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAACAAACCTGGTAAAGAAGAC
GGCAACAAGCCTGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACGGCAACGGAGTA
CATGTCGTTAAACCTGGTGATACAGTAAATGACATTGCAAAAGCAAACGGCACTACTGCT
GACAAAATTGCTGTAGATAACAAATTAGCTGATAAAAACATGATCAAACCTGGTCAAGAA
CTTGTTGTTGATAAGAAGCAACCAGCAAACCATGCAGATGCTAACAAAGCTCAAGCATTA
CCAGAAACTGGTGAAGAAAATCCATTCATCGGTACAACTGTATTTGGTGGATTATCATTA
GCGTTAGGTGCAGCGTTATTAGCTGGACGTCGTCGCGAACTATAA
ATGGCGCAACACGATGAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCTAAC
TTAAATGCTGATCAACGCAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGT
GCTAACGTTTTAGGTGAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCG
CAACAAAATAACTTCAACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCT
AACTTAAACGAAGCGCAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAA
AGCACTAACGTTTTAGGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGAT
AACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTA
AACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCT
AACCTATTGTCAGAAGCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAA
TTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAA
GAACAACGCAATGGTTTCATCCAAAGCCTAAAAGATGACCCAAGCCAAAGCGCTAACCTT
TTAGCAGAAGCTAAAAAGCTAAATGATGCTCAAGCACCAAAAGCTGACAACAAATTCAAC
AAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAA
CGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCA
GAAGCTAAAAAGCTAAACGATGCTCAAGCACCAAAAGAGGAAGACAATAACAAGCCTGGC
AAAGAAGACAATAACAAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGACAAC
AACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGCAAAGAAGACGGCAACAAGCCTGGT
AAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACAAC
AAAAAACCTGGTAAAGAAGACGGCAACAAGCCTGGCAAAGAAGATGGCAACAAACCTGGT
AAAGAAGATGGTAACGGAGTACATGTCGGCGGATCCAGTGAAAACACGCAACAAACTTCA
ACTAAGCACCAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAA
GTATTACATCTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGC
GAACACCCAGAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCA
GACCGACGTGTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACT
GAACAAGAAAAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAA
GTTTGGGTAGAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCG
GATAAAGCAATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATAT
GAAGCTAACTCAAAATTACCTAAAGATTTACGTGATAAAAACAACCGCTTTGTAGAAAAA
GTTTCAATTGAAAAAGCA
ATGGCGCAACACGATGAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCTAAC
TTAAATGCTGATCAACGCAATGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGT
GCTAACGTTTTAGGTGAAGCTCAAAAACTTAATGACTCTCAAGCTCCAAAAGCTGATGCG
CAACAAAATAACTTCAACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCT
AACTTAAACGAAGCGCAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAA
AGCACTAACGTTTTAGGTGAAGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGAT
AACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTGAATATGCCTAACTTA
AACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCT
AACCTATTGTCAGAAGCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAA
TTCAACAAAGAACAACAAAATGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAA
GAACAACGCAATGGTTTCATCCAAAGCCTAAAAGATGACCCAAGCCAAAGCGCTAACCTT
TTAGCAGAAGCTAAAAAGCTAAATGATGCTCAAGCACCAAAAGCTGACAACAAATTCAAC
AAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAA
CGTAACGGCTTCATCCAAAGCCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCA
GAAGCTAAAAAGCTAAACGATGCTCAAGCACCAAAAGAGGAAGACAATAACAAGCCTGGC
AAAGAAGACAATAACAAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGACAAC
AACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGCAAAGAAGACGGCAACAAGCCTGGT
AAAGAAGACAACAAAAAACCTGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACAAC
AAAAAACCTGGTAAAGAAGACGGCAACAAGCCTGGCAAAGAAGATGGCAACAAACCTGGT
AAAGAAGATGGTAACGGAGTACATGTCGGCGGATCCAGTGAAAACACGCAACAAACTTCA
ACTAAGCACCAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAA
GTATTACATCTAAAAGGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGC
GAACACCCAGAACGTGCACAAGAAGTATTCTCTGAATCACTTAAAGACAGCAAGAACCCA
GACCGACGTGTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACTTAACT
GAACAAGAAAAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAA
GTTTGGGTAGAATCAGTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCG
GATAAAGCAATTAAAGATTTCCAAGATAACAAAGCACCACACGATAAATCAGCAGCATAT
GAAGCTAACTCAAAATTACCTAAAGATTTACGTGATAAAAACAACCGCTTTGTAGAAAAA
GTTTCAATTGAAAAAGCAACTAGTGGCCACCATCACCATCACCATTAA
atgGCGCAACACGATGAAGCTCAACAAAATGCTTTTTATCAAGTCTTAAATATGCCTAACTTAAATGCTGATCAACGCAA
TGGTTTTATCCAAAGCCTTAAAGATGATCCAAGCCAAAGTGCTAACGTTTTAGGTGAAGCTCAAAAACTTAATGACTCTC
AAGCTCCAAAAGCTGATGCGCAACAAAATAACTTCAACAAAGATCAACAAAGCGCCTTCTATGAAATCTTGAACATGCCT
AACTTAAACGAAGCGCAACGTAACGGCTTCATTCAAAGTCTTAAAGACGACCCAAGCCAAAGCACTAACGTTTTAGGTGA
AGCTAAAAAATTAAACGAATCTCAAGCACCGAAAGCTGATAACAATTTCAACAAAGAACAACAAAATGCTTTCTATGAAA
TCTTGAATATGCCTAACTTAAACGAAGAACAACGCAATGGTTTCATCCAAAGCTTAAAAGATGACCCAAGCCAAAGTGCT
AACCTATTGTCAGAAGCTAAAAAGTTAAATGAATCTCAAGCACCGAAAGCGGATAACAAATTCAACAAAGAACAACAAAA
TGCTTTCTATGAAATCTTACATTTACCTAACTTAAACGAAGAACAACGCAATGGTTTCATCCAAAGCCTAAAAGATGACC
CAAGCCAAAGCGCTAACCTTTTAGCAGAAGCTAAAAAGCTAAATGATGCTCAAGCACCAAAAGCTGACAACAAATTCAAC
AAAGAACAACAAAATGCTTTCTATGAAATTTTACATTTACCTAACTTAACTGAAGAACAACGTAACGGCTTCATCCAAAG
CCTTAAAGACGATCCTTCAGTGAGCAAAGAAATTTTAGCAGAAGCTAAAAAGCTAAACGATGCTCAAGCACCAAAAGAGG
AAGACAATAACAAGCCTGGCAAAGAAGACAATAACAAGCCTGGCAAAGAAGACAACAACAAGCCTGGTAAAGAAGACAAC
AACAAGCCTGGTAAAGAAGACAACAACAAGCCTGGCAAAGAAGACGGCAACAAGCCTGGTAAAGAAGACAACAAAAAACC
TGGTAAAGAAGATGGCAACAAGCCTGGTAAAGAAGACAACAAAAAACCTGGTAAAGAAGACGGCAACAAGCCTGGCAAAG
AAGATGGCAACAAACCTGGTAAAGAAGATGGTAACGGAGTACATGTCGGCggatccGAGGAGAATTCAGTACAAGACGTT
AAAGATTCGAATACGGATGATGAATTATCAGACAGCAATGATCAGTCTAGTGATGAAGAAAAGAATGATGTGATCAATAA
TAATCAGTCAATAAACACCGACGATAATAACCAAATAATTAAAAAAGAAGAAACGAATAACTACGATGGCATAGAAAAAC
GCTCAGAAGATAGAACAGAGTCAACAACAAATGTAGATGAAAACGAAGCAACATTTTTACAAAAGACCCCTCAAGATAAT
ACTCATCTTACAGAAGAAGAGGTAAAAGAATCCTCATCAGTCGAATCCTCAAATTCATCAATTGATACTGCCCAACAACC
ATCTCACACAACAATAAATAGAGAAGAATCTGTTCAAACAAGTGATAATGTAGAAGATTCACACGTATCAGATTTTGCTA
ACTCTAAAATAAAAGAGAGTAACACTGAATCTGGTAAAGAAGAGAATACTATAGAGCAACCTAATAAAGTAAAAGAAGAT
TCAACAACAAGTCAGCCGTCTGGCTATACAAATATAGATGAAAAAATTTCAAATCAAGATGAGTTATTAAATTTACCAAT
AAATGAATATGAAAATAAGGCTAGACCATTATCTACAACATCTGCCCAACCATCGATTAAACGTGTAACCGTAAATCAAT
TAGCGGCGGAACAAGGTTCGAATGTTAATCATTTAATTAAAGTTACTGATCAAAGTATTACTGAAGGATATGATGATAGT
GAAGGTGTTATTAAAGCACATGATGCTGAAAACTTAATCTATGATGTAACTTTTGAAGTAGATGATAAGGTGAAATCTGG
TGATACGATGACAGTGGATATAGATAAGAATACAGTTCCATCAGATTTAACCGATAGCTTTACAATACCAAAAATAAAAG
ATAATTCTGGAGAAATCATCGCTACAGGTACTTATGATAACAAAAATAAACAAATCACCTATACTTTTACAGATTATGTA
GATAAGTATGAAAATATTAAAGCACACCTTAAATTAACGTCATACATTGATAAATCAAAGGTTCCAAATAATAATACCAA
GTTAGATGTAGAATATAAAACGGCCCTTTCATCAGTAAATAAAACAATTACGGTTGAATATCAAAGACCTAACGAAAATC
GGACTGCTAACCTTCAAAGTATGTTTACAAACATAGATACGAAAAATCATACAGTTGAGCAAACGATTTATATTAACCCT
CTTCGTTATTCAGCCAAGGAAACAAATGTAAATATTTCAGGGAATGGTGATGAAGGTTCAACAATTATAGACGATAGCAC
AATAATTAAAGTTTATAAGGTTGGAGATAATCAAAATTTACCAGATAGTAACAGAATTTATGATTACAGTGAATATGAAG
ATGTCACAAATGATGATTATGCCCAATTAGGAAATAATAATGATGTGAATATTAATTTTGGTAATATAGATTCACCATAT
ATTATTAAAGTTATTAGTAAATATGACCCTAATAAGGATGATTACACGACTATACAGCAAACTGTGACAATGCAGACGAC
TATAAATGAGTATACTGGTGAGTTTAGAACAGCATCCTATGATAATACAATTGCTTTCTCTACAAGTTCAGGTCAAGGAC
AAGGTGACTTGCCTCCTGAAAAAACTTATAAAATCGGAGATTACGTATGGGAAGATGTAGATAAAGATGGTATTCAAAAT
ACAAATGATAATGAAAAACCGCTTAGTAATGTATTGGTAACTTTGACGTATCCTGATGGAACTTCAAAATCAGTCAGAAC
AGATGAAGATGGGAAATATCAATTTGATGGATTGAAAAACGGATTGACTTATAAAATTACATTCGAAACACCTGAAGGAT
ATACGCCGACGCTTAAACATTCAGGAACAAATCCTGCACTAGACTCAGAAGGTAATTCTGTATGGGTAACTATTAATGGA
CAAGACGATATGACGATTGATAGTGGATTTTATCAAACACCTAAATACAGCTTAGGGAACTATGTATGGTATGACACTAA
TAAAGATGGTATTCAAGGTGATGATGAAAAAGGAATCTCTGGAGTTAAAGTGACGTTAAAAGATGAAAACGGAAATATCA
TTAGTACAACTACAACCGATGAAAATGGAAAGTATCAATTTGATAATTTAAATAGTGGTAATTATATTGTTCATTTTGAT
AAACCTTCAGGTATGACTCAAACAACAACAGATTCTGGTGATGATGACGAACAGGATGCTGATGGGGAAGAAGTTCATGT
AACAATTACTGATCATGATGACTTTAGTATAGATAACGGATACTATGATGACGAAggatccAGTGAAAACACGCAACAAA
CTTCAACTAAGCACCAAACAACTCAAAACAACTACGTAACAGATCAACAAAAAGCTTTTTATCAAGTATTACATCTAAAA
GGTATCACAGAAGAACAACGTAACCAATACATCAAAACATTACGCGAACACCCAGAACGTGCACAAGAAGTATTCTCTGA
ATCACTTAAAGACAGCAAGAACCCAGACCGACGTGTTGCACAACAAAACGCTTTTTACAATGTTCTTAAAAATGATAACT
TAACTGAACAAGAAAAAAATAATTACATTGCACAAATTAAAGAAAACCCTGATAGAAGCCAACAAGTTTGGGTAGAATCA
GTACAATCTTCTAAAGCTAAAGAACGTCAAAATATTGAAAATGCGGATAAAGCAATTAAAGATTTCCAAGATAACAAAGC
ACCACACGATAAATCAGCAGCATATGAAGCTAACTCAAAATTACCTAAAGATTTACGTGATAAAAACAACCGCTTTGTAG
AAAAAGTTTCAATTGAAAAAGCAactagtGGCCACCATCACCATCACCATTAA
MAQHDEAQQNAFYQVLNMPNLNADQRNGFIQSLKDDPSQSANVLGEAQKLNDSQAPKADAQQNNFNKDQQSAFYEILNMP
NLNEAQRNGFIQSLKDDPSQSTNVLGEAKKLNESQAPKADNNFNKEQQNAFYEILNMPNLNEEQRNGFIQSLKDDPSQSA
NLLSEAKKLNESQAPKADNKFNKEQQNAFYEILHLPNLNEEQRNGFIQSLKDDPSQSANLLAEAKKLNDAQAPKADNKFN
KEQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNDAQAPKEEDNNKPGKEDNNKPGKEDNNKPGKEDN
NKPGKEDNNKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDNKKPGKEDGNKPGKEDGNKPGKEDGNGVHVGGSEENSVQDV
KDSNTDDELSDSNDQSSDEEKNDVINNNQSINTDDNNQIIKKEETNNYDGIEKRSEDRTESTTNVDENEATFLQKTPQDN
THLTEEEVKESSSVESSNSSIDTAQQPSHTTINREESVQTSDNVEDSHVSDFANSKIKESNTESGKEENTIEQPNKVKED
STTSQPSGYTNIDEKISNQDELLNLPINEYENKARPLSTTSAQPSIKRVTVNQLAAEQGSNVNHLIKVTDQSITEGYDDS
EGVIKAHDAENLIYDVTFEVDDKVKSGDTMTVDIDKNTVPSDLTDSFTIPKIKDNSGEIIATGTYDNKNKQITYTFTDYV
DKYENIKAHLKLTSYIDKSKVPNNNTKLDVEYKTALSSVNKTITVEYQRPNENRTANLQSMFTNIDTKNHTVEQTIYINP
LRYSAKETNVNISGNGDEGSTIIDDSTIIKVYKVGDNQNLPDSNRIYDYSEYEDVTNDDYAQLGNNNDVNINFGNIDSPY
IIKVISKYDPNKDDYTTIQQTVTMQTTINEYTGEFRTASYDNTIAFSTSSGQGQGDLPPEKTYKIGDYVWEDVDKDGIQN
TNDNEKPLSNVLVTLTYPDGTSKSVRTDEDGKYQFDGLKNGLTYKITFETPEGYTPTLKHSGTNPALDSEGNSVWVTING
QDDMTIDSGFYQTPKYSLGNYVWYDTNKDGIQGDDEKGISGVKVTLKDENGNIISTTTTDENGKYQFDNLNSGNYIVHFD
KPSGMTQTTTDSGDDDEQDADGEEVHVTITDHDDFSIDNGYYDDEGSSENTQQTSTKHQTTQNNYVTDQQKAFYQVLHLK
GITEEQRNQYIKTLREHPERAQEVFSESLKDSKNPDRRVAQQNAFYNVLKNDNLTEQEKNNYIAQIKENPDRSQQVWVES
VQSSKAKERQNIENADKAIKDFQDNKAPHDKSAAYEANSKLPKDLRDKNNRFVEKVSIEKATSGHHHHHH
Claims (13)
- それぞれがIgG結合ドメインを含む2つの異なる単離されたブドウ球菌ポリペプチドを含む免疫原性組成物であって、黄色ブドウ球菌に由来する単離されたプロテインAポリペプチド又は5つのIgG結合ドメインを含むその断片と、黄色ブドウ球菌に由来する単離されたSbiポリペプチド又は2つのIgG結合ドメインを含むその断片と、別のブドウ球菌抗原とを含み、ヒト被験体に投与した後、ブドウ球菌IgG結合タンパク質の中和をもたらす、上記免疫原性組成物。
- 単離されたプロテインAポリペプチドが、配列番号31〜40に対して少なくとも90%の同一性を有する配列又はIgG結合ドメインを含むその断片を有する、請求項1記載の免疫原性組成物。
- 単離されたSbiポリペプチドが、配列番号3〜11に対して少なくとも90%の同一性を有する配列又はIgG結合ドメインを含むその断片を有する、請求項1記載の免疫原性組成物。
- 単離されたプロテインAポリペプチド又はその断片が単離されたSbiポリペプチド又はその断片と共有結合して融合タンパク質を形成している、請求項1〜3のいずれか1項に記載の免疫原性組成物。
- 融合タンパク質が、配列番号41〜42若しくは76の配列に対して少なくとも90%の同一性を有するポリペプチド配列を有する、請求項4記載の免疫原性組成物。
- (a)配列番号31〜40からなる群より選択されるアミノ酸配列に対して少なくとも90%の同一性を有するアミノ酸配列を有するプロテインA部分、又は少なくとも5つのIgG結合ドメインを含むその免疫原性断片と、(b)配列番号3〜11からなる群より選択されるアミノ酸配列に対して少なくとも90%の同一性を有するアミノ酸配列を有するSbi部分、又は少なくとも2つのIgG結合ドメインを含むその免疫原性断片とを含むポリペプチドであって、ヒト被験体に投与した後、ブドウ球菌IgG結合タンパク質の中和をもたらす、上記ポリペプチド。
- 配列番号41又は42又は76に対して少なくとも90%の同一性を有するアミノ酸配列を有する、請求項6記載のポリペプチド。
- (a)配列番号64〜72からなる群より選択されるポリヌクレオチド配列に対して少なくとも90%の同一性を有するプロテインAコード領域、又は少なくとも5つのIgG結合ドメインをコードするその断片と、(b)配列番号45〜53からなる群より選択されるポリヌクレオチド配列に対して少なくとも90%の同一性を有するSbiコード領域、又は少なくとも2つのIgG結合ドメインをコードするその断片と、を含むポリヌクレオチド。
- (a)配列番号31〜40からなる群より選択されるアミノ酸配列に対して少なくとも90%の同一性を有するプロテインA様部分、又は少なくとも5つのIgG結合ドメインを含むその免疫原性断片と、(b)配列番号3〜11からなる群より選択されるアミノ酸配列に対して少なくとも90%の同一性を有するSbi様部分、又は任意選択で少なくとも2つのIgG結合ドメインを含んでもよいその免疫原性断片と、を含む融合タンパク質をコードするポリヌクレオチド。
- 請求項1〜5のいずれか1項に記載の免疫原性組成物又は請求項6若しくは7記載のポリペプチド、及び薬学的に許容される担体を含むワクチン。
- 請求項1〜5のいずれか1項に記載の免疫原性組成物又は請求項6若しくは7記載のポリペプチドに薬学的に許容される賦形剤を添加するステップを含む、請求項10記載のワクチンの製造方法。
- ブドウ球菌疾患の治療又は予防に使用するための請求項1〜5のいずれか1項に記載の免疫原性組成物。
- ブドウ球菌疾患を治療又は予防するための医薬の製造における請求項1〜5のいずれか1項に記載の免疫原性組成物の使用。
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GB0526038A GB0526038D0 (en) | 2005-12-21 | 2005-12-21 | Immunogenic composition |
GB0526038.5 | 2005-12-21 | ||
PCT/EP2006/069944 WO2007071692A2 (en) | 2005-12-21 | 2006-12-19 | Immunogenic composition |
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EP (1) | EP1962890B1 (ja) |
JP (2) | JP5780693B2 (ja) |
CA (1) | CA2634898A1 (ja) |
ES (1) | ES2558703T3 (ja) |
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WO2021215462A1 (ja) * | 2020-04-23 | 2021-10-28 | ブライトパス・バイオ株式会社 | 改良ペプチドワクチン |
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GB0610776D0 (en) * | 2006-05-31 | 2006-07-12 | Univ Bath | Novel applications for staphylococcus aureus Sbi protein |
WO2008127457A2 (en) | 2006-12-06 | 2008-10-23 | Repligen Corporation | Nucleic acids encoding recombinant protein a |
BRPI1010307B1 (pt) | 2009-04-03 | 2021-07-27 | University Of Chicago | Polipeptídeos variantes de proteína a (spa), composição imunogênica compreendendo os mesmos, vacina, método de produção da referida vacina, bem como uso dos referidos polipeptídeos |
NZ612315A (en) | 2009-04-14 | 2014-10-31 | Novartis Ag | Compositions for immunising against staphylococcus aureus |
CA2779798C (en) | 2009-09-30 | 2019-03-19 | Novartis Ag | Conjugation of staphylococcus aureus type 5 and type 8 capsular polysaccharides |
CN102971009A (zh) | 2009-10-30 | 2013-03-13 | 诺华有限公司 | 金黄色葡萄球菌5型和8型荚膜多糖的纯化 |
ES2655701T3 (es) * | 2010-07-02 | 2018-02-21 | The University Of Chicago | Composiciones y métodos relacionados con variantes de la proteína A (SpA) |
US9095540B2 (en) * | 2010-09-09 | 2015-08-04 | The University Of Chicago | Methods and compositions involving protective staphylococcal antigens |
US9988439B2 (en) | 2011-12-23 | 2018-06-05 | Nicholas B. Lydon | Immunoglobulins and variants directed against pathogenic microbes |
WO2013096948A1 (en) * | 2011-12-23 | 2013-06-27 | Lydon Nicholas B | Immunoglobulins and variants directed against pathogenic microbes |
CN102698260B (zh) * | 2012-04-20 | 2013-09-25 | 西北农林科技大学 | 预防山羊葡萄球菌***炎的亚单位疫苗的制备方法及应用 |
US9974848B2 (en) | 2013-11-14 | 2018-05-22 | Duke University | Tetanus toxoid and CCL3 improve DC vaccines |
JP2016540764A (ja) * | 2013-12-04 | 2016-12-28 | グリコヴァキシン アーゲー | 大腸菌で合成された糖タンパク質ワクチンによる黄色ブドウ球菌感染の予防 |
CN103694322B (zh) * | 2013-12-09 | 2016-08-17 | 成都欧林生物科技股份有限公司 | 金黄色葡萄球菌SpA5突变体及其制备方法和应用 |
SI3122378T1 (sl) | 2014-03-26 | 2020-03-31 | Glaxosmithkline Biologicals S.A. | Mutantni stafilokokni antigeni |
GB201619965D0 (en) * | 2016-11-25 | 2017-01-11 | Univ Of Bath The | Immunogenic compositions comprising sbi protein and uses thereof |
GB201802339D0 (en) | 2018-02-13 | 2018-03-28 | Glaxosmithkline Biologicals Sa | Immunogenic composition |
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GB0107661D0 (en) * | 2001-03-27 | 2001-05-16 | Chiron Spa | Staphylococcus aureus |
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KR101359930B1 (ko) * | 2004-09-22 | 2014-02-12 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | 스태필로코쿠스에 대한 예방접종에 사용하기 위한 면역원성조성물 |
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2005
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- 2006-12-19 US US12/097,820 patent/US20080311146A1/en not_active Abandoned
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2013
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EP1962890A2 (en) | 2008-09-03 |
WO2007071692A2 (en) | 2007-06-28 |
JP2009520758A (ja) | 2009-05-28 |
GB0526038D0 (en) | 2006-02-01 |
WO2007071692A3 (en) | 2007-09-13 |
US20080311146A1 (en) | 2008-12-18 |
US20150125481A1 (en) | 2015-05-07 |
EP1962890B1 (en) | 2015-11-11 |
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CA2634898A1 (en) | 2007-06-28 |
ES2558703T3 (es) | 2016-02-08 |
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