KR20160002880A - 엔도솜 포집을 극복하기 위해 설계된 인공 전사 인자 - Google Patents

엔도솜 포집을 극복하기 위해 설계된 인공 전사 인자 Download PDF

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KR20160002880A
KR20160002880A KR1020157031592A KR20157031592A KR20160002880A KR 20160002880 A KR20160002880 A KR 20160002880A KR 1020157031592 A KR1020157031592 A KR 1020157031592A KR 20157031592 A KR20157031592 A KR 20157031592A KR 20160002880 A KR20160002880 A KR 20160002880A
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알버트 네우트체트너
조세프 플래머
앨리스 헉슬리
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알리오프타 아게
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Abstract

본 발명은 세포에 형질 도입 후 엔도솜 포집(endosomal entrapment)을 극복하기 위해 설계된, 특히 유전자 프로모터를 표적으로 하는 다지성 아연 집게 단백질(polydactyl zinc finger protein)을 포함하는 인공 전사 인자에 관한 것이다. 이러한 인공 전사 인자는 억제(inhibitory) 또는 활성(activatory) 단백질 도메인에 융합된 다지성 아연 집게 단백질, 핵 국소화 서열(nuclear localization sequence), 단백질 전달 영역(protein transduction domain), 및 엔도솜 특이적 프로테아제 인식 부위를 포함한다. 이러한 전달 가능(transducible)한 인공 전사 인자는 단상부족성(haploinsufficient) 유전자의 핵 수용체 단백질 또는 생산물인, 막-결합 수용체 단백질에 의하거나 조절되는 질병의 치료에 특히 유용하다.

Description

엔도솜 포집을 극복하기 위해 설계된 인공 전사 인자{Artificial transcription factors engineered to overcome endosomal entrapment}
본 발명은 세포 내로 형질 도입 후 엔도솜 포집(endosomal entrapment)을 극복하기 위해 설계된 특히 유전자 프로모터를 타겟으로 하는 다지성 아연 집게 단백질(polydactyl zinc finger protein) 및 단백질 전달 영역(protein transduction domain)에 관한 것이다.
인공 전사 인자(Artificial transcription factors)는 유전자 발현을 조절하는데 유용한 도구로 제안되어 왔다 (Sera T., 2009, Adv Drug Deliv Rev 61, 513-526). 자연적으로 발생하는 많은 전사 인자는, 유전자 전사의 억제 또는 활성화 모두를 통해 유전자 발현에 영향을 미치며, 특정 DNA 서열의 인식을 위한 복잡한 특정 도메인을 갖는다. 이는 하나가 자신의 특이성 및 대상 유전자(들)을 수정하고자하는 조작에 매력적이다. 그러나, 전사 인자의 특정 클래스는 소위 아연 집게(zinc finger; ZF) 도메인으로 불리는 모듈을 포함하며, 따라서 유전 공학에 이용된다. 아연 집게는 짧은(30개 아미노산) DNA가 거의 독립적으로 세 DNA 염기쌍을 표적하는 모티프(motifs)에 결합한다. 같이 융합된 여러 아연 집게를 포함하는 단백질은 따라서 긴 DNA 서열을 인식할 수 있다. 육량체(hexameric)의 아연 집게 단백질(ZFP)은 18 염기 쌍(bp) DNA 타겟을 인식하며, 전체 인간 게놈에서 거의 유일하다. 아연 집게에 대하여 초기에는 완전히 문맥 독립적으로 생각되었지만, 몇 가지 상황에 특이적으로 더욱 깊이 있는 분석이 밝혀졌다(Klug A., 2010, Annu Rev Biochem 79, 213-231). ZF 모듈의 결합 특이성을 변화시키는 아연 집게 인식 표면에서 특정 아미노산의 변이는 5'-GNN-3', 5'-CNN-3', 5'-ANN-3'의 대부분 및 5'-TNN-3' 코돈에 대한 정의된 ZF 빌딩 블록 결과는 나타낸다(즉, 소위 Barbas 모듈이라 불림, Dreier B., Barbas C.F. 3rd et al., 2005, J Biol Chem 280, 35588-35597 참조). 인공 전사 인자에 대한 초기 연구가 공지된 3 bp 표적 서열과 함께 미리 선택된 아연 집게와의 결합을 기초로 한 합리적 설계에 집중된 반면에, 아연 집게의 특정 문맥 특이성의 실현이 FACS 분석을 이용한 박테리아 또는 효모 원 하이브리드(bacterial or yeast one hybrid), 파아지 디스플레이(phage display), 분류된 리보솜 디스플레이(compartmentalized ribosome display) 또는 생체 내 선택(in vivo selection)과 같은 정교한 방법을 이용하여 정보를 얻은 큰 아연 집게 라이브러리의 생성을 필요로 하였다.
이러한 인공 아연 집게 단백질을 이용하여, 인간 게놈 내의 DNA 위치(loci)는 높은 특이성으로 표적될 수 있다. 따라서, 이러한 아연 집게 단백질은 관심 있는 유전자의 발현의 조절 결과 특이적 프로모터 서열에 대한 전사-조절성 활성과 함께 단백질 도메인 수송하는데 이상적인 도구이다. 전사의 침묵(silencing)을 위한 적절한 도메인은 N-말단(서열번호 1) 또는 C-말단(서열번호 2) KRAB 도메인과 같은 Krueppel-관련된 도메인(KRAB), Sin3-상호작용 도메인(SID, 서열번호 3) 및 ERF 억제자 도메인(ERD, 서열번호 4)이며, 반면에 유전자 전사의 활성화는 헤르페스 바이러스 심플렉스(herpes virus simplex) VP16(서열번호 5) 또는 VP64(tetrameric repeat of VP16, 서열번호 6) 도메인(Beerli R.R. 등, 1998, Proc Natl Acad Sci USA 95, 14628-14633)을 통해 얻는다. 전사 활성을 부여하는 것으로 간주되는 추가적인 도메인은 CJ7 (서열번호 7), p65-TA1 (서열번호 8), SAD (서열번호 9), NF-1 (서열번호 10), AP-2 (서열번호 11), SP1-A (서열번호 12), SP1-B (서열번호 13), Oct-1 (서열번호 14), Oct-2 (서열번호 15), Oct-2_5x (서열번호 16), MTF-1 (서열번호 17), BTEB-2 (서열번호 18) 및 LKLF (서열번호 19)이다. 또한, 유전자 온톨로지(gene ontology) GO: 0001071 (http://amigo.geneontology.org/cgi bin/amigo/term_details?term=GO:0001071)에 의해 정의된 단백질의 전사적 활성 도메인은 표적 단백질의 전사 조절을 달성하는 것으로 간주 된다. 조작된 아연 집게 단백질뿐 아니라 조절 도메인(regulatory domains)을 포함하는 융합 단백질은 인공 전사 인자로써 참조 된다.
작은 분자 약물은 특정 기능의 높은 보존 때문에 항상 선택적으로 주어진 단백질 패밀리의 특정 구성원을 대상으로 할 수 없지만, 생물학적 제제(biologicals)은 항체 지반의 새로운 의약품과 같이 큰 특이성을 부여한다. 그러나, 거의 모든 생물학적 제제는 지금까지 세포 외로 활성 한다. 특히 상기 언급한 인공 전사 인자는 치료적으로 유용한 방법으로 유전자 전사에 영향을 미치는 것에 적합하다. 그러나, 작용 부위에 이러한 인자의 전달(핵)은 용이하지 않아서, 치료적 인공 전사 인자의 유용성 저해는, 예를 들면 세포 형질 전환을 위한 면역적 및 잠재적인 이러한 방법의 모든 단점을 가지는 레트로 바이러스 전달(Lund C.V. et al., 2005, Mol Cell Biol 25, 9082-9091)에 이어서 접근한다.
소위 불리는 단백질 형질 도입 도메인(PTDs)는 세포질/핵질(cytosol/nucleoplasm)로 원형질 막(plasma membrane)을 걸쳐 단백질 전좌(translocation)를 촉진하기 위해 도시되었다. TAT 펩티드 (서열번호 20)로 유도된 HIV, mT02 (서열번호 21), mT03 (서열번호 22), R9 (서열번호 23), ANTP (서열번호 24) 및 기타와 같은 짧은 펩티드는 화물 단백질(cargo proteins)에 융합될 때 세포 타입 독립적 macropinocytotic uptake를 유도하는 것으로 보여진다(Wadia J.S. et al., 2004, Nat Med 10, 310-315). 세포질에 도착하면, 이러한 융합 단백질은 생물학적 활성을 갖는 것으로 나타났다. 흥미롭게도, 잘못 접힌 단백질은 세포 내 샤페론(chaperones)의 작용을 통해 대부분 단백질 수송 후 기능화될 수 있다. 그러나, 세포에 치료적 화물(therapeutic cargo)을 수송하기 위해 단백질 수송 도메인의 사용을 위한 주요한 장애는 핵과 같은 다른 세포 내 국부화에 대한 엔도좀 구획으로부터 이러한 단백질의 배출이 제한된다는 것이다(Koren E and Torchilin V.P., 2012, Trends in Mol Med 18, 385-393). 단백질의 수송 후 화물 단백질의 엔도좀 배출을 증가시키기 위해 필요한 것은 오랫동안 인식되는 것이며, 엔도솜 배출의 향상을 위한 두 주요 접근 방식이 사용된다: 우선, HA2 (서열번호 25), KALA (서열번호 26) 또는 GALA (서열번호 27)과 같은 소위 융합생성 단백질(fusogenic peptides)이라 불리는 펩티드의 공동 수송(co-delivery)은 세포의 세포질 내로 단백질 수송을 증가시키기 위한 것으로 보여진다. 엔도솜 내부에, 이러한 펩티드는 자신의 성분을 해방시키는 이러한 소체(vesicles)의 파단(rupture)에 이르는 엔도솜 막과 상호작용이 가능하다. 두 번째로, 엔도솜 구획을 방해하는 것으로 알려진 클로로퀸(chloroquine)과 같은 lysosomotropic 제제는 엔도솜으로부터 화물 단백질의 배출을 증가시키는 것으로 보여진다. 엔도섬 배출을 증가시키는 다른 접근 방법은 융해 지질(fusogenic lipids) 및 PEI와 같은 막 파열(membrane-disruptive) 폴리머를 포함한다(El Sayed A. et al., 2009, AAPS J 11, 13-22). 지금까지, 단백질 수송 후 화물 단백질(cargo proteins)의 엔도 배출(endosomal escape)을 증가시키기 위한 모든 접근 방법은 엔도솜 막을 방해할 수 있는 제제를 포함한다.
알려진 모든 약물 표적의 큰 비율은 종종 오프 타겟 활성(off-target activities)으로 간주 될 수 있는 작은 분자 약물의 작용에 의해 자극되거나 차단되는 수용체 분자이다. 이러한 수용체에 대한 예는 히스타민 H1 수용체 또는 알파- 및 베타-아드레도 수용체(adrenoreceptors)가 있지만, 일반적인 단백질은 유전자 온톨로지 GO:0004888 및 GO:0004930에 의해 정의된다.
혈관 활성 엔도텔린(vasoactive endothelin) 시스템은 다양한 질병의 발명 기전에 중요한 역할을 한다. 한편, 엔도텔린은 혈액 공급 조절에 관여하고 있으며, 한편으로는 저산소증(hypoxia)에 의해 유도된 사건(cascade of events)에서 중요한 역할을 한다. 엔도텔린은, 예를 들어, 뇌혈관 또는 망막 혈관 장벽 및 신생 혈관(neovascularisation)의 고장에 관여한다. 엔도텔린은 또한 신경 퇴행(neurodegeneration)뿐 아니라 통증 감각(pain sensation) 또는 갈증 느낌(thirst feeling)의 임계치의 조절에 관여한다. 엔도텔린은 또한 안압 조절(intraocular pressure)에 관여한다.
엔도텔린의 작용은 일반적으로 혈관 주변 평활근 세포에 위치하는, 주로 엔도텔린 수용체 A인 이의 동종 수용체에 의해 매개 된다. 엔도텔린 시스템(전신적 또는 국소적)의 영향은 예컨데 지주막하(subarachnoidal) 출혈 또는 뇌출혈(brain hemorrhages)과 같은 많은 질환의 치료를 위한 것이다. 엔도텔린은 또한 다발 경화증(multiple sclerosis)의 과정에 영향을 미친다. 엔도텔린은 (폐)고혈압(hypertension)에 기여할 뿐만 아니라 동맥 저혈압(arterial hypotension), 심근증(cardiomyopathy)에 기여하며 레이노 증후군(Raynaud syndrome), 이형 협심증(variant angina) 및 심혈관계 질환(cardiovascular diseases)에 기여한다. 엔도텔린은 당뇨병성 신장증(diabetic nephropathy) 및 당뇨병성 망막증(diabetic retinopathy)에 관여한다. 눈에 있어서, 이는 또한 녹내장성 신경 변성(glaucomatous neurodegeneration), 망막 정맥 폐쇄(retinal vein occlusion), 거대 세포 관절염(giant cell arthritis), 색소성 망막염(retinitis pigmentosa), 연령 관련 황반 변성(age related macula degeneration), 중심 장액성 맥락 망막 병증(central serous chorioretinopathy), Morbus Leber, Susac 증후군, 안구 출혈(intraocular hemorrhages), 망막 신경교증(epiretinal gliosis) 및 기타 병리학적 조건에 대한 역할을 한다.
눈은 높은 산소 요구량을 충족하기에 충분한 균형잡힌 관류에 강하게 의존하는 정교한 기관이다. 충분하고 안정적인 산소 공급을 제공하지 않으면 정상 또는 정규화된 안압임에도 불구하고 질병의 진행과 함께 녹내장 환자에게서 괄찰되는 것과 같은 신경 교세포 활성화(glial activation) 및 신경 파손을 이끄는 허혈-재관류(ischemia-reperfusion) 손상이 발생한다. 불충분한 혈액 공급은 또한 당뇨성 망막 병증 또는 노화에 따른 망막 변성 동안 발생하는 것과 같은 추가적인 망막 손상의 가능성과 함께 신생 혈관의 폭주에 의해서 저산소증으로 연결된다. 안구 조직 관류는 복잡한 제어하에 있으며 혈압, 안압뿐만 아니라 혈관 직경을 조절하는 국부적 인자에 의존한다. 이러한 국부적 인자는 예를 들면 엔도텔린, 강한 혈관 수축 활성을 갖는 짧은 펩티드를 언급할 수 있다. 엔도텔린의 세 가지 아형(ET-1, ET-2, 및 ET-3)은 혈관 벽에 편재된 엔도텔린 세포에 의해 분비된 전구체 분자로부터의 전환된 효소인 엔도텔린에 의해 생산된다. 성숙한 ET를 위한 두 동족 수용체는 ETRA 및 ETRB으로 알려져 있다. ETRA인 혈관벽을 형성하고 혈관 수축(vasoconstriction)을 촉진하는 평활근에 위치하는 반면에, ETRB는 주로 내피세포(endothelial cells)에서 발현하며 산화 질소 방출을 촉진함으로써 vasodilatatory 역할을 하여 평활근 이완을 일으킨다. ETRA 및 ETRB은 7 개의 트랜스멤브레인 헬릭스 수용체에 결합된 G-단백질의 큰 클래스에 속한다. ETRA 및 ETRB에 대한 ET의 결합은 G-단백질 활성화를 나타내고, 따라서 세포 내 칼슘 농도 증가를 유발하여 세포 활성의 광범위한 배열을 유발한다.
ET 시스템의 영향은 약학적으로 여러 상황에서 유용할 수 있으며, 여기서 ET 수준은 상승하고 ET가 망막 정맥 폐쇄, 녹내장성 신경 퇴행, 색소성 망막염, 거대 세포 동맥염, 중심 장액 맥락 망막 병증, 다발성 경화증, 시신경염, 류마티스 관절염, Susac 증후군, 방사선 망막 병증, 망막 신경교증, 섬유 근육통 및 당뇨 망막 병증과 같은 해로운 방식에서 작용한다. 이를 위해, ETRA의 하향 조절이 질병의 결과를 변조하는데 도움이 된다. 그러나 예를 들어, 각막 외상이나 각막 궤양에서 복구하는 동안 각막 상처 치유를 촉진하기 위해 특정 상환에서, ETRA의 상향 조절 및 이에 따른 ET에 대한 향상된 민감성은 바람직할 수 있다.
ETRB-매개 신호는 예를 들면 암 줄기세포 유지 및 종양 성장 동안과 같은 병리 생리학적(pathophysiological) 과정에 연결된다. 또한, 녹내장에서 ETRB의 억제가 신경보호(neuroprotective) 역할을 하는 것을 보이는 반면 ETRB의 상향 조절은 녹내장 신경 퇴행과 연관된다. 또한, ETRB는 염증에서 상향조절된다.
리포폴리사카라이드(LPS)와 같은 박테리아 세포 벽 성분은 다양한 질병의 발병 기전에 중요한 역할을 한다. 신체에서 LPS의 존재는 면역 시스템에 의해 다루어질 필요가 있는 박테리아 감염을 지적한다. LPS는 그람 음성균의 일반적인 구성 요소이기 때문에, LPS는 면역 시스템을 활성화할 수 있는 소위 위험 신호를 구성한다. LPS는 다양한 위험 신호 또는 박테리아 또는 바이러스 감염에 관련된 병원체 분자 패턴(PAMPs)의 인식에 연관된 Toll-유사 수용체의 큰 패밀리의 구성군인 Toll-like receptor 4 (TLR4)에 의해 인식된다. 위험 신호로써 LPS의 인식은 선천성 면역(innate immunity)의 중요한 부분인 반면에, TLR4 수용체의 과자극 또는 장기간 자극은 만성 염증과 관련된 다양한 병리적 상태에 연관된다. 예로는 알콜성 간질환, 비알콜성 지방간 질환, 비알콜성 지방간염, 만성 간염 B 또는 C 바이러스(HCV) 감염, 및 HIV-HCV 동시 감염과 같은 다양한 간 질환이다. TLR4 신호와 관련된 다른 질환은 류마티스 관절염, 동맥 경화증, 건선, 크론병, 포도막염, 콘택트 렌즈 관련 각막염 및 각막 염증이다. 또한, TLR4 매개 신호는 화학 요법에 대한 암 진행 및 저항에 관여한다.
면역 글로불린의 아이소타입 E(IgE)는 적응 면역 시스템의 일부이며 감염으로부터 보호뿐만 아니라 종양 변형에 관여한다. IgE는 비만 세포(mast cells) 및 호염기성(basophile) 세포에 위치한 높은 친화성 IgE 수용체(FCER1)에 의해 결합된다. 알레젠(allergens)으로 불리는 특이적 항원을 통한 이러한 복합체의 가교결합 후 FCER1에 대한 IgE의 결합은 알레르기 반응을 일으키는 비만 세포 및 호염기구로부터의 다양한 인자의 방출을 유도한다. 이러한 인자는 히스타민(histamine), 류코트리엔(leukotrienes), 다양한 사이토카인이지만, 또한 라이소자임(lysozyme), 트립타아제(tryptase) 또는 β-hexosaminidase이다. 이러한 인자의 방출은 알레르기성 비염, 천식, 습진 및 아나필락시스(anaphylaxis) 같은 알레르기 질환과 연관된다.
핵 수용체는 리간드 활성화 전사 인자의 단백질 상과(superfamily)이다. 그들은, 다른 세포 수용체와 달리, 세포질 또는 핵질에 현지화된 수용성 단백질이다. 핵 수용체를 위한 리간드는 이들 사이에서, 친유성 분자, 스테로이드 및 갑상선 호르몬, 지방산 및 담즙산, 레티노산, 비타민 D3 및 프로스타글란딘(prostaglandins)이다(McEwan I.J., Methods in Molecular Biology: The Nuclear Receptor Superfamily, 505, 3-17). 핵 수용체 이량체화 같은 리간드가 결합하면, 전사 인자 특이적 DNA에 특이적 결합을 일으키는 것이 유전자 발현의 활성화 또는 억제 모두를 야기하는 리간드 반응적 유전자 프로모터 내부의 요소에 반응한다. 핵 수용체가 스테로이드 및 중요 대사와 같은 많은 다양한 작용 호르몬의 활성의 매개 책임이 있음을 감안할 때, 핵 수용체의 miss- 및 기능장애(dysfunction)는 많은 질병의 자연 경과에 관여한다.
핵 수용체의 활성을 조절하기 위한 작용제(agonists) 또는 길항제(antagonists)를 사용은 치료 목적을 위해 이용되었다. 작용제 덱사메타손(dexamethasone)과 같은 코르티코스테로이드(corticosteroids)를 이용한 glucocorticoid receptor (NR3C1) 기능의 조절은 염증성 질환에 영향을 미치는 공통 임상 실행이다. 핵 수용체 활성의 다른 조절은 경구 피임(oral contraception)에서 예시되며, 여기서 에스트로겐 수용체(ESR1/ER) 및 프로게스테론 수용체의 활성화는 여성에서 수정을 방지하기 위해 사용된다. 또 다른 예로는, 플루타미드(flutamide) 또는 바이칼루타미드(bicalutamide)와 같은 항 안드로젠을 이용한 안드로젠 수용체(AR)의 차단은 AR 의존적인 전립선 암의 치료에 유용함을 입증하였다. 또한, 에스트로겐 합성의 차단에 의한 에스트로겐 수용체의 차단 및 이로써 에스트로겐의 가용성은 여성의 유방암 또는 남성의 유방비대증(gynaecomastia) 치료의 표준이다.
유전적 돌연변이는 많은 유전 질환의 핵심이다. 일반적으로, 이와 같은 변이는 이들의 유전 모드에 따라 우성(dominant) 또는 열성(recessive)으로 분류되며, 우성 돌연변이는 모계 또는 부계의 오직 하나의 유전자가 카피되어도 질병 표현형을 야기할 수 있고, 반면에 질병을 일으키는 열성 돌연변이는 모계 및 부계 모두로부터 유전자 카피가 돌연변이가 될 필요가 있다. 우성 돌연변이는 우성 음성 작용(dominant-negative action) 또는 단상부족(haploinsufficiency)에 각각에 의한, 두 일반적인 메커니즘의 하나에 의해 질병을 야기할 수 있다. 우성 음성 돌연변이의 경우, 유전자 생산물은 독성 및 질환 표현형을 야기하는 새롭고 비정상적인 작용을 얻는다. 예를 들면 상기 유전자 복합체의 적절한 기능을 방지하는 돌연변이에 따른 다량 단백질 복합체의 서브유닛이다. 우성 방식에서 지배적인 질환은 단상부족에 의해 야기되며, 여기서 상기 돌연변이가 유도한 질환은 영향받은 유전자를 불활성화시켜서 유전자 도즈(dose)를 낮추는데 효과적이다. 이러한 상황에서, 두 번째로, 온전한 유전자 카피는 정상적인 기능을 위해 충분한 유전자 생산물을 제공하는 것이 가능하다. 약 12,000 인간 유전자는 단상부족인 것으로 추정되며(Huang et al., 2010, PLoS Genet. 6(10), e1001154), 약 300 유전자가 이러한 질환과 연관되어 있다고 알려져 있다.
신경 세포의 생존은 매우 많은 신경 퇴행성 질환의 중심에서 미토콘드리아 장애와 미토콘드리아 기능에 따라 달라진다(Karbowski M., Neutzner A., 2012, Acta Neuropathol 123(2), 157-71). ATP의 형태로 에너지를 제공하는 자신의 필수적인 기능 외에, 미토콘드리아는 칼슘 버퍼링, 다양한 이화(catabolic)뿐만 아니라 대사 과정 및 프로그램된 세포 사멸에 결정적으로 참여하고 있다. 미토콘드리아의 중요한 기능은 미토콘드리아를 유지하고 미토콘드리아 장애에 이어서 세포 사멸을 방지하기 위해 많은 세포 메커니즘에서 반영된다(Neutzner A. et al., 2012, Semin Cell Dev Biol 23, 499-508). 이러한 과정 중에서 중요한 역할은 균형 잡힌 미토콘드리아 형태로 동적 미토콘드리아 네트워크의 유지 보수를 수행한다. 이는, Drp1, Fis1, MFF, MiD49 및 MiD51의 경우에서 미토콘드리아의 분열 또는 Mfn1, Mfn2 및 OPA1의 경우에서 미토콘드리아 세관의 융합을 촉진하는 소위 미토콘드리아 morphogens에 의해 달성된다. 미토콘드리아 융합 손실은 ATP 생산의 손실을 촉진하는 것으로 알려져 있으며 신경 퇴행성 장애와 연관된 신경 세포 사멸에 대한 프로세스를 연결하는 자극 아포토시스 세포를 민감하게 하기 때문에 미토콘드리아 형태를 균형화 잡는 것은 필수적이다.
미토콘드리아 융합의 과정에서 중요한 역할은 시신경 위축(optic atrophy) 1 또는 OPA1이다. OPA1은 OPA1 유전자에 의해 암호화되는 큰 GTPase이며 미토콘드리아 융합에 필수적이다. 또한, OPA1는 cristae의 성분으로써 미토콘드리아 구조인 내부를 유지하는데 중요한 역할을 한다. OPA1 유전자 발현의 하향 조절은 융합의 손실 및 아폽토시스 자극에 세포를 민감하게 하여 미토콘드리아 단편화를 야기하는 것으로 나타났다. OPA1에서 돌연변이는 약 70%의 Kjer의 시신경 병증(Kjer's optic neuropathy) 또는 염색체 우성 위축(autosomal dominant atrophy; ADOA)인 것으로 확인되었다. 대분분의 인구에서, ADOA는 1/10,000 및 3/100,000 사이에서 일반적이며 유아기 때부터 시작하여 시력 감소가 서서히 진행되는 특징이 있다. 시력장애는 가벼운 것에서부터 정식적인 맹검의 범위이며, 망막 신경절 세포(RGCs)의 느린 변성에 의해 야기되며 비가역적이다. 대부분의 경우, ADOA는 비-증후군(non-syndromic)이나, 약 15%의 청각 신경 난청(sensori-neural hearing loss)와 같은 신생 근육 증상, 안외(extra-ocular) 환자가 발생한다. 지금까지, 본 질병에 관한 가능한 치료는 없었다. 흥미롭게도, 특정 OPA1 대립유전자는 정상 안압에 연결되었으나, 높은 안압 녹내장이 아닌, 정상적인 미토콘드리아 생리를 유지하기 위해 OPA1의 중요성을 다시 강조하였다.
발명의 요약
본 발명은 억제(inhibitory) 또는 활성(activatory) 단백질 도메인에 융합된 유전자 프로모터를 특이적으로 표적으로 하는 다지성 아연 집게 단백질(polydactyl zinc finger protein), 핵 국소화 서열(nuclear localization sequence), 단백질 전달 영역(protein transduction domain), 및 엔도솜 특이적 프로테아제 인식 부위를 포함하는 인공 전사 인자(artificial transcription factor), 및 상기 인공 전사 인자를 포함하는 약학적 조성물에 관한 것이다.
또한, 본 발명은 유전자 발현을 조절하기 위한 인공 전사 인자의 용도, 및 상기 유전자 발현의 조절이 유용한 질병을 치료하기 위한 용도에 관한 것이다.
구체적인 실시형태에서, 본 발명의 인공 전사 인자에 의해 표적화된 유전자 프로모터는 수용체 유전자 프로모터이다.
다른 구체적인 실시형태에서, 본 발명의 인공 전사 인자에 의해 표적화된 유전자 프로모터는 핵 수용체 유전자 프로모터이다.
다른 구체적인 실시형태에서, 본 발명의 인공 전사 인자에 의해 표적화된 유전자 프로모터는 단상부족성(haploinsufficient) 이다.
다른 구체적인 실시형태에서, 상기 엔도좀 특이적 프로테아제 인식 부위는 카텝신 인식 부위(cathepsin recognition site)이며, 바람직하게는 카텝신 B 인식 부위(cathepsin B recognition site)이고, 예를들어, 카텝신 B 인식 부위는 생체 외 기판 프로레닌(prorenin) 상에서 카텝신 B에 포함된다(QPMKRLTLGN, 서열번호 28).
다른 구체적인 실시형태에서, 본 발명은 억제(inhibitory) 또는 활성(activatory) 단백질 도메인에 융합된 유전자 프로모터를 특이적으로 표적으로 하는 다지성 아연 집게 단백질(polydactyl zinc finger protein), 핵 국소화 서열(nuclear localization sequence), 및 엔도솜 특이적 프로테아제 인식 부위를 포함하는 인공 전사 인자(artificial transcription factor) 변이체에 관한 것이다.
구체적인 실시형태에서, 상기 수용체 유전자 프로모터는 엔도텔린(endothelin) 수용체 A 프로모터(서열번호 29)이다. 다른 구체적인 실시형태에서 본 발명은 엔도텔린 수용체 A 수준을 낮추거나 증가시키는, 엔도텔린에 대한의 세포 반응 영향에 사용하기 위한 인공 전사 인자에 관한 것이며, 엔도텔린에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 엔도텔린에 의해 조절되는 질병의 치료 방법에 관한 것이다.
구체적인 실시형태에서, 상기 수용체 유전자 프로모터는 엔도텔린(endothelin) 수용체 B 프로모터(서열번호 30)이다. 다른 구체적인 실시형태에서 본 발명은 엔도텔린 수용체 B 수준을 낮추거나 증가시키는, 엔도텔린에 대한 세포 반응 영향에 사용하기 위한 인공 전사 인자에 관한 것이며, 엔도텔린에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 엔도텔린에 의해 조절되는 질병의 치료 방법에 관한 것이다.
다른 구체적인 실시형태에서, 상기 수용체 유전자 프로모터는 Toll-유사 수용체 4(Toll-like receptor 4) 프로모터(서열번호 31)이다. 다른 구체적인 실시형태에서 본 발명은 Toll-유사 수용체 4 프로모터 수준을 낮추거나 증가시키는, 지질다당류(lipopolysaccharide)에 대한 세포 반응 영향에 사용하기 위한 인공 전사 인자에 관한 것이며, 지질다당류에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 지질다당류에 의해 조절되는 질병의 치료 방법에 관한 것이다.
다른 구체적인 실시형태에서, 상기 수용체 유전자 프로모터는 높은 친화력 글로불린 입실론 수용체 알파 소단위(high-affinity immunoglobulin epsilon receptor subunit alpha; FcER1A) 프로모터(서열번호 32)이다. 다른 구체적인 실시형태에서 본 발명은 높은 친화력 글로불린 입실론 수용체 알파 소단위 프로모터 수준을 낮추거나 증가시키는, 면역글로불린 E(immunoglobulin E; IgE)에 대한 세포 반응 영향에 사용하기 위한 인공 전사 인자에 관한 것이며, IgE에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 IgE에 의해 조절되는 질병의 치료 방법에 관한 것이다.
다른 구체적인 실시형태에서, 상기 핵 수용체 유전자의 프로모터 영역은 글루코코르티코이드 수용체(glucocorticoid receptor) 프로모터(서열번호 33)이다. 다른 구체적인 실시형태에서 본 발명은 글루코코르티코이드 수용체 프로모터 수준을 낮추거나 증가시키는, 글루코코르티코이드에 대한 세포 반응 영향에 사용하기 위한 글루코코르티코이드 수용체 프로모터를 표적으로 하는 인공 전사 인자에 관한 것이며, 글루코코르티코이드에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 글루코코르티코이드 수용체 프로모터를 표적으로 하는 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 글루코코르티코이드에 의해 조절되는 질병의 치료 방법에 관한 것이다.
다른 구체적인 실시형태에서, 상기 핵 수용체 유전자의 프로모터 영역은 안드로겐 수용체(androgen receptor) 프로모터(서열번호 34)이다. 다른 구체적인 실시형태에서 본 발명은 안드로겐 수용체 프로모터 수준을 낮추거나 증가시키는, 테스토스테론(testosterone)에 대한 세포 반응 영향에 사용하기 위한 안드로겐 수용체 프로모터를 표적으로 하는 인공 전사 인자에 관한 것이며, 테스토스테론에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 안드로겐 수용체 프로모터를 표적으로 하는 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 테스토스테론에 의해 조절되는 질병의 치료 방법에 관한 것이다.
다른 구체적인 실시형태에서, 상기 핵 수용체 유전자의 프로모터 영역은 에스트로겐(estrogen receptor) 프로모터(서열번호 35)이다. 다른 구체적인 실시형태에서 본 발명은 에스트로겐 수용체 프로모터 수준을 낮추거나 증가시키는, 에스트로겐에 대한 세포 반응 영향에 사용하기 위한 에스트로겐 수용체 프로모터를 표적으로 하는 인공 전사 인자에 관한 것이며, 에스트로겐에 의해 조절되는 질병의 치료, 특히 안과 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 에스트로겐 수용체 프로모터를 표적으로 하는 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 에스트로겐에 의해 조절되는 질병의 치료 방법에 관한 것이다.
또한, 본 발명은 단상부족성(haploinsufficient) 유전자 프로모터로부터의 발현 증가 및 단상부족성 유전자 프로모터에 의하거나 영향을 받는 질병 치료에 사용하기 위한 상기 인공 전사 인자의 용도에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 단상부족성 유전자 프로모터를 표적으로 하는 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 단상부족성에 의하거나 조절되는 질병의 치료 방법에 관한 것이다.
구체적인 실시형태에서, 단상부족성 유전자 프로모터는 OPA1 프로모터(서열번호 36)이다. 이러한 구체적인 실시형태에서, 본 발명은 OPA1 유전자의 발현을 향상시키고, 낮은 OPA1 수준에 의해 야기되거나 조절되는 질병, 특히 눈 질환의 치료에 사용하기 위한 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 치료적으로 유효한 양을 투여하는 것을 포함하는 OPA1에 영향을 받는 질병의 치료 방법에 관한 것이다.
본 발명은 또한 본 발명의 인공 전사 인자를 암호화하는 핵산, 이를 포함하는 벡터 및 상기 벡터를 포함하는 숙주 세포에 관한 것이다.
도 1: 프로테아제-민감성 전달가능( transducible )한 인공 전사 인자
유전자(G)의 프로모터 영역(P)에 특이적인, 단백질 전달 도메인(protein transduction domain; PTD), 엔도솜 특이적 프로테아제 절단 부위(endosome-specific protease cleavage site; PS), 전사 조절 활성 도메인(domain with transcription regulating activity;RD), 핵 국소화 서열(nuclear localization sequence; NLS), 및 다지성 아연 집게(polydactyl zinc finger; ZF) 단백질을 포함하는 인공 전사 인자는 엔도시토시스(endocytotic) 메커니즘을 통해 세포 내로 들어온다. 도 1A에서 상기 인공 전사 인자는 핵(n)에 효율적으로 도달할 수 없는 엔조솜 구획(e) 안에 갇혀있다. 도 1B에서, 엔도솜-특이적 프로테아제(가위로 표시)는 엔도좀이 성숙되는 동안 활성화되며, PS를 인식하고 인공 전사 인자를 절단하여 RD-NLS-ZFn로부터 PTD를 분리한다. 도 1C를 보면, 엔도솜 소포의 파멸에 따라, 절단된 인공 전사 인자는 엔도솜 구획을 남길 수 있고 핵으로 운반된다. 유전자 G의 프로모터 영역 P에서 표적 부위에 결합함으로써, mRNA(m)의 생산은 상향 또는 하향 조절되며(+ 또는 -), 조절 도메인 RD의 전사 조절 활성에 따른다.
도 2: ETRA 를 표적하는 인공 전사 인자
HeLa 세포는 SID 도메인을 포함하는 ETRA-특이적 인공 전사 인자인 AO74V, 및 ETRA 프로모터(AO74V)를 포함하는 Gaussia luciferase/SEAP 수용체 플라스미드와 함께 공동 형질 감염시켰다. AO74V 대신 YFP를 발현하는 세포는 대조군(c)으로 사용하였다. 형질감염 48시간 후, 루시퍼라제 활성을 측정하였고, SEAP 활성에 표준화하였으며 대조군 비율에서 상대적인 루시퍼라아제 활성(RLuA)으로 나타내었다.
도 3: ETRA -특이적 인공 전사 인자는 내인성 ETRA 유전자의 발현을 억제할 수 있다
(A)+(B) 테트라사이클린(tetracycline) 유도성 프로모터의 대조군 하에서 ETRA_TS+74 (AO74V로 표지된)을 표적으로 하는 ETRA-특이적 인공 전사 인자를 안정적으로 발현하는 HEK 293 FlpIn TRex 세포는 24시간 동안 테트라사이틀린(tet)와 함께 처리되거나 처리되지 않고 ETRA nRNA 수준은 정량적 RT-PCR을 이용하여 측정된다. 안정적으로 통합된 공 벡터(M으로 표지) 또는 모든 시스테인 잔기가 결여된 AO74V의 비활성 버전을 포함하는 세포는 대조군으로 사용되는 아연 복합체(C로 표지)에 관여한다. 구조체의 발현은 AAVS1 safe harbor(패널 B의 세포)로 상동 재조합 또는 TALEN-매개 이중 가닥 수리(double-strand repair)를 통해, 이러한 세포에서 존재하는 FlpIn 부위(패널 A의 세포)로 통합된다. (C) AAVS1 locus에서 AO74V를 위한 테트라사이클린 유도성 발현 구조체(AO74V로 표지), 비활성 AO74V (C로 표지) 또는 공벡터 대조군(M으로 표지)를 포함하는 HeLa세포는 24시간 동안 테트라사이클린(tet)로 유도되거나 처리하지 않은 채로 남기고, ETRA mRNA 수준은 RT-PCT에 의해 정량된다. 이러한 유도되지 않은 세포에 상대적으로 테트라사이클린 유도 세포의 ETRA 발현(FC)의 세 번의 독립적인 실험의 평균 변화를 나타내었다. 오차 막대는 SD로 나타내었다.
도 4: ETRA -특이적 인공 전사 인자는 ET -1 의존적 칼슘 신호( calcium signaling)를 차단한다
SID 도메인을 포함하는 ETRA-특이적 인공 전사 인자인 AO74V를 위한 테트라사이클린 유도 가능한 발현 벡터로 안정적 형질 감염된 HEK 293 FlpIn TRex 세포는 1 μg/ml의 테트라사이클린(B)으로 유도되거나 유도되지 않고(A) 0 (채워진 원), 100 (빈 원), 또는 1000 (삼각형) ng/ml의 ET-1으로 처리된다. 칼슘 플럭스(Calcium flux)는 측정되었으며 시간(초, s) 대 베이스 라인의 비율에서 상대적인 형광(RF)으로 나타내었다.
도 5: ETRA -특이적 인공 전사 인자는 ET -1 의존성 인간 자궁 평활근 세포 수축을 차단한다
ETRA+74VrepSNPS는 ET-1 의존성 인간 자궁 평활근 세포(hUtSMC)의 수축을 차단한다. hUtSMC는 3차원 콜라겐 격자에 삽입되었다. C= 대조군으로써 버퍼로 처리된 세포. B= 버퍼 및 ET-1으로 처리된 세포. V= ETRA+74VrepSNPS 및 ET-1으로 처리된 세포. RLA= 대조군(C)의 %에서 상대적인 격자 영역. 자세한 사항을 아래 설명되어 있다.
도 6: ETRA +74 VrepSNPS 와 비교하여 ETRA +74 VrepS 의 증가된 엔도솜 배출( escape )
HeLa 세포는 2시간 동안 1 μM 카텝신(cathepsin) B-둔감성(insensitive) ETRA+74VrepSNPS (NPS로 표시) 또는 카텝신 B-민감성(sensitive) ETRA+74VrepS(PS로 표시)로 처리된 OptiMEM 배지에서 2시간 동안 배양되었다. 세포는 고정되어 인공 전사 인자를 검출하기 위해 항-myc 에피토프(epitope) 항체를 이용하여 염색되었고, 이미지를 촬영하였다. 인공 전사 인자의 핵 수입(NI)은 이미지 분석을 이용하여 측정하고, 최대 형광 신호의 백분율로 나타내었다. 200 cells/experiment로 세 번의 독립적인 실험의 평균을 나타내었다.
도 7: 카텝신 B 인식 부위의 봉입체는 루시퍼라제 리포터 분석에서 ETRA -특이적 인공 전사 인자의 활성을 증가시킨다
하이브리드 CMV/TS+74 (target site for ETRA+74VrepS/NPS) 의 대조군 하의 Gaussia 루시퍼라제의 안정적 발현 및 구성적 CMV 프로모터의 대조군 하의 알칼리 포스파타아제가 분비되는 HEK 293 FlpIn 세포는 ETRA+74VrepS (카텝신 부위 포함- PS로 표지) 또는 ETRA+74VrepSNPS (카텝신 부위 없음- NPS로 표지)으로 처리되었다. 모든 아연 복합체 시스테인 잔기가 결여된 ETRA+74VrepS 비활성 변이체의 처리는 대조군(C로 표지)로 사용되었다. 루시퍼라제 및 분비된 알칼리성 포스파타제 활성은 처리 후 24시간에 측정되었다. 루시퍼라제 활성은 분비된 알칼리 포스파타제 활성으로 표준화되며 대조군의 백분율로써 나타내었다. 세 번의 기술 반복으로써 세 번의 독립적인 실험의 평균을 나타내었다. 통계적 유의성은 Tukey HSD posthoc test와 함께 one-way ANOVA를 이용하여 분석하였다. C로 표시된 그룹, NPS 및 PS는 유의적인 차이가 있다(P<0.05).
도 8: 카텝신 B 인식 부위의 봉입체는 루시퍼라아제 리포터 분석에서 TLR4 특이적 인공 전사 인자의 활성을 증가시킨다
하이브리드 CMV/TS-222 (target site for TLR4-222ArepS/NPS)의 대조군 하에서 Gaussia 루시퍼라제의 안정적 발현 및 구조적 CMV 프로모터의 대조군 하에서 알칼리성 포스파타제가 분비되는 HEK 293 FlpIn 세포는 TLR4-222ArepS (카텝신 부위 포함- PS로 표지) 또는 TLR4-222ArepSNPS (카텝신 부위 없음- NPS로 표지)으로 처리되었다. 관련 없는 인공 전사 인자로 처리된 것은 대조군(C로 표지)으로 사용하였다. 루시퍼라제 및 알카리 포스파타제의 분비 활성은 처리 후 24시간에 측정하였다. 루시퍼라제 활성은 분비된 알칼리 포스파타제 활성으로 표준화되었고 대조군의 백분율로 표시되었다. 세 번의 기술 반복으로써 세 번의 독립적인 실험의 평균을 나타내었다. 오차 막대는 SD로 나타내었다.
도 9: 카텝신 B 인식 부위의 봉입체는 루시퍼라아제 리포터 분석에서 AR 특이적 인공 전사 인자의 활성을 증가시킨다
하이브리드 CMV/TS-236 (target site for AR-236ArepS/NPS)의 대조군 하에서 Gaussia 루시퍼라제의 안정적 발현 및 구조적 CMV 프로모터의 대조군 하에서 알칼리성 포스파타제가 분비되는 HEK 293 FlpIn 세포는 AR-236ArepS (카텝신 부위 포함- PS로 표지) 또는 AR-236ArepSNPS (카텝신 부위 없음- NPS로 표지)로 처리되었다. 관련 없는 인공 전사 인자로 처리된 것은 대조군(C로 표지)으로 사용하였다. 루시퍼라제 및 알카리 포스파타제의 분비 활성은 처리 후 24시간에 측정하였다. 루시퍼라제 활성은 분비된 알칼리 포스파타제 활성으로 표준화되었고 대조군의 백분율로 표시되었다. 세 번의 기술 반복으로써 세 번의 독립적인 실험의 평균을 나타내었다. 오차 막대는 SD로 나타내었다.
도 10: 카텝신 B 인식 부위의 봉입체는 루시퍼라아제 리포터 분석에서 FcER1A 특이적 인공 전사 인자의 활성을 증가시킨다
하이브리드 CMV/TS-147 (target site for IgER-147ArepS/NPS)의 대조군 하에서 Gaussia 루시퍼라제의 안정적 발현 및 구조적 CMV 프로모터의 대조군 하에서 알칼리성 포스파타제가 분비되는 HEK 293 FlpIn 세포는 IgER-147ArepS (카텝신 부위 포함- PS로 표지) 또는 IgER-147ArepSNPS (카텝신 부위 없음- NPS로 표지)로 처리되었다. 관련 없는 인공 전사 인자로 처리된 것은 대조군(C로 표지)으로 사용하였다. 루시퍼라제 및 알카리 포스파타제의 분비 활성은 처리 후 24시간에 측정하였다. 루시퍼라제 활성은 분비된 알칼리 포스파타제 활성으로 표준화되었고 대조군의 백분율로 표시되었다. 세 번의 기술 반복으로써 세 번의 독립적인 실험의 평균을 나타내었다. 오차 막대는 SD로 나타내었다.
도 11: ETRA +74 VrepS 의 처리는 ET -1 의존적 인간 관상 동백 혈관의 수축을 감소한다
분리된 인간 관상 동백 혈관 고리는 3일 동안 1 μM의 ETRA-특이적, 카텝신 B-민감성 인공 전사 인자 ETRA+74VrepS 또는 버퍼 대조군과 함께 배양되었다. 혈관 고리는 와이어 근운동 기록기(myograph)로 계수하였으며 ET-1의 농도 증가 뿐만 아니라 혈관 수축에 대한 혈관의 반응은 측정되었다. 혈관의 ET-1반응은 U46619 반응의 백분율로 나타내었다. 한 사람의 심장 기증자로부터 조건 당 8 혈관의 평균을 나타내었다. 오차 막대는 SD로 나타내었다.
도 12: IgER -147 ArepS 와 함께 인간화 NSG 마우스의 치료는 과민성 쇼크( anaphylactic shock)의 유도 후 사멸의 지연을 야기한다
인간화 NSG 마우스(NOD-scid IL2Rgnull implanted with human CD34+ cells)는 항-dinitrophenyl(anti-DNP) IgE 항체 주입 5일 및 2일 전 용매대조군(C로 표지) 또는 IgER-147ArepS으로 처리되었다. DNP-BSA (DNP coupled to bovine serum albumin)의 주입은 BSA의 주입을 대조군(-AS로 표지)으로 사용하는 반면, 아나필락시스(+AS로 표지)를 유도하기 위해 사용하였다. 시간(t[분]으로 표지)에 걸쳐 생존한 동물(NOSA)의 수를 나타내었다. 용매 대조군(원)으로 처리된 마우스에서 아나필락시스의 유도는 동물의 빠른 죽음으로 이르게 하고, 반면에 FCER1A 특이적 인공 전사 인자 IgER-147ArepS의 전처리는 처리된 동물의 생존을 연장시켰다.
본 발명은 특이적 유전자 프로모터(gene promoter)를 표적으로 하는 다지성(polydactyl) 아연 집게(zinc finger) 단백질로 구성된 인공 전사 인자(artificial transcription factor)에 관한 것으로, 예를 들면 수용체 유전자의 프로모터(receptor gene promoter), 특히 멤브레인-결합(membrane-bound) 수용체 유전자 프로모터 또는 핵 수용체(nuclear receptor) 유전자 프로모터 또는 단상부족성(haploinsufficient) 유전자 프로모터, 퓨전된 억제(inhibitory) 또는 활성(activatory) 단백질 도메인, 핵 이동 서열(nuclear localization sequence), 단백질 전달 도메인(protein transduction domain) 및 엔도좀-특이적 프로테아제 인식 부위(endosome-specific protease recognition site), 및 이러한 인공 전사 인자(artificial transcription factor)로 구성된 약학적 조성물. 또한, 본 발명은 유전자의 발현을 조절하는 인공 전사 인자의 용도에 관한 것으로, 예를 들어 멤브레인-결합 또는 핵 수용체 유전자같은 수용체 유전자, 또는 단상부족성(haploinsufficient) 유전자 및 유전자에 의해 암호화된 단백질의 조절 및 유발에 의한 질병의 치료, 본 발명의 전사 인자에 의해 표전된 프로모터, 예를 들어, 멤브레인-결합 또는 핵 수용체 단백질과 같은 수용체 단백질, 또는 단상부족성(haploinsufficient) 유전자에 의해 생산된 단백질.
본 발명의 문맥에서, 프로모터는 당업계에 공지된 유전자 조졀 영역(regulatory region)으로 정의된다. 다시 이러한 상황에서, 유전자뿐만 아니라 단백질 또는 RNA의 생산하는 유전자 조절 서열을 포함하는 유전적 영역(regulatory sequences)은 당업계에 공지된 대로 정의된다.
본 발명의 문맥에서, "특이적(specifically)" 유전자 프로모터를 타겟팅하는 다지성(polydactyl) 아연 집게(zinc finger) 단백질은 단백질이 그것의 DNA 타겟을 향해 20 nM 또는 그 이하의 결합 친화도(binding affinity)를 갖는다는 것을 의미한다.
본 발명의 문맥에서, 멤브레인-결합 수용체 유전자는 단백질의 생산 또는 세포 반응을 유발하는 세포 멤브레인을 가로지르는 리간드 결합의 신호 전달 및 세포 외 리간드와 결합이 가능한 단백질 복합체의 일부분인 단백질이다. 또한, 본 발명의 문맥에서, 핵 수용체(nuclear receptor)는 세포 투과성(cell-permeable ) 리간드 결합을 할 핵(nucleus) 또는 세포질(cytosol)로 이동된 수용성 단백질의 생산을 유발하며 그들의 동족 리간드 결합시 유전자 발현 조절을 위해 전사 인자 또는 부수적인(accessory) 전사인자로 작동할 수 있다.
본 발명의 맥락에서, 단상부족성(haploinsufficient) 유전자는 오직 유전자에서 두 가지 기능성 유전자 카피(copy)가 존재할 경우 모든 상황에서 모든 유형의 세포에 충분한 유전자 생산을 생산할 수 있는 유전자로 정의된다. 따라서, 단상부족성(haploinsufficient) 유전자의 하나의 유전자 카피(copy)의 돌연변이는 일부 또는 모든 생리적 상황(physiological circumstances)에서 유기체의 모든 또는 일부의 세포에 유전자 생산 발생이 불충분해지는 것을 유발한다.
본 발명의 문맥에서, 엔도좀-특이적(endosome-specific) 프로테아제(protease) 인식 부위는 단백질 서열이며, 이는 엔도조말(endosomal) 내 구획에서 프로테아제 존재에 의해 서열-특이적(sequence-specific) 방법으로 인식되고, 절단된다. 다시 본 발명의 문맥에서, 단백질 전달 도메인(protein transduction domain)은 플라즈마 멤브레인(plasma membrane)에서 세포 내 구획(intracellular compartment)으로 관통하는 인공 전사 인자(artificial transcription factors)와 같은 수송할 수 있는 단백질로 정의된다.
많은 질환의 치료는 세포 수용체 신호를 조절하는데 기초한다. 예로 고혈압(high blood pressure)에서 베타 차단제(beta blockers)는 베타 아드레날린 수용체(beta adrenergic receptors)의 기능을 저해하고, 우울증에서 세로토닌 흡수 저해제는 아고니스트(agonist)의 농도를 증가시키며, 세로토닌 수용체 신호를 증가시키고, 녹내장에서 프로스타글란딘(prostaglandin) 유사체가 프로스타글란딘 수용체를 활성화 시키고, 이어 안압(intraocular pressure)을 감소시킨다. 전통적으로 아고니스트(agonist) 또는 안타고니스트(antagonists) 수용체 형태 중 어느 하나의 작은 분자는 치료 목적으로 수용체 신호에 영향을 주어 이용되고 있다. 그러나, 세포 수용체 신호는 수용체 단백질 발현의 직접적 조절에 의해 영향을 받을 수 있다.
수용체 발현 수준의 직접 조절할 수 있는 병리학적 과정, 예를 들면, 다음과 같다: 선천성 심질환(congenital heart disease)으로 인해 울혈성 심부전(congestive heart failure)을 각진 환자는 베타-아드레노셉터(beta-adrenoceptors)의 상향 조절(upregulation)로부터 이익이 있고, 심근에서 상기 수용체의 하향 조절(downregulation)은 수술 후 심부전(post-operative heart failure)의 위험과 관련이 있다. 파킨슨 병에 있어서, 도파민성(dopaminergic) 약물의 치료는 도파민 수용체의 가용성을 억제하며, 따라서 도파민 수용체의 상향 조절은 도파민성 약제의 효율을 향상시킬 수 있다, 간질의 경우 해마에서 칸나비노이드(cannabinoid) 수용체의 불충분한 발현은 병인학(disease etiology)과 관계가 있고, 칸나비노이드 수용체의 상향 조절은 간질 환자를 위해 가능한 치료가 될 수 있다.
수용체 단백질의 단상부족(haploinsufficiency)에 의한 유전적 질병을 위해 성장 지연(retardation)을 유발하는 인슐린-유사 성장 인자 1 수용체뿐만 아니라 다른, 남아있는 기능적인 수용체 유전자의 추가적인 활성은 환자에게 유익할 것이다. 또한 다른 사람들 사이에서 병리학적 자기 면역(pathological autoimmunity)의 유도 및 영구 보존은 Toll-유사 수용체(Toll-like receptors)로부터의 부적절한 신호와 연결되어 있다. 따라서, Toll-유사 수용체의 하향 조절(downregulation)은 다양한 자기 면역 질환의 악순환을 깰 것이다. 알레르기성 질환에서 높은 친화도의 IgE 수용체를 통한 IgE-매게 신호의 예방은 알레르기 반응을 관리하는데 유용하다. 암에 있어서, 성장 인자 수용체의 하향 조절 또는 세포 외 세포간질 수용체(extracellular matrix receptors)의 상향 조절은 암 진행 예방에 효과적이다.
이러한 수용체 분자는 단백질의 7-멤브레인(seven-transmembrane) 또는 G 단백질 결합 수용체(G protein coupled receptor, GPCR) 패밀리로 불리며, 플라스마 멤브레인에서 수용체에 접착된 일곱 트랜스멤브레인(transmembrane) 도메인으로 성질을 나타내며, G 단백질 독립적인(G protein dependent) 신호 캐스케이드(cascade)를 갖는다. 예로 이러한 단백질은 엔도텔린(endothelin)의 수용체 A 및 B이다. 다른 수용체 단백질은 단일 트랜스멤브레인 지역을 통해 접착되고, 예로 리포 다당류(lipopolysaccharide)의 수용체, Toll-유사 수용체 4(Toll-like receptor 4), 또는 IL-4 수용체와 같은 다양한 사이토카인(cytokine) 수용체이다. 다른 수용체는 다중 결합은 단백질 복합체(multimeric protein complexes)로 구성되며, 예를 들어, 알파(alpha), 베타(beta) 및 감마(gamma) 사슬로 구성된 IgE 항체의 높은 친화성의 수용체, 또는 알파, 베타, 감마, 델타(delta), 엡실론(epsilon) 및 제타(zeta) 사슬로 구성된 T-세포 수용체이다. 따라서 하기 용어 "수용체 분자(receptor molecule)"는 활성의 매우 다른 모드를 갖는 다른 단백질 패밀리로 부터의 단백질을 포함한다.
본 발명에서 고려되는 수용체는 다음에 의해 암호화되는(encoded) 인간 수용체 분자(human receptor molecules )이다; HTR1A , HTR1B , HTR1D , HTR1E , HTR1F , HTR2A, HTR2B , HTR2C , HTR4 , HTR5A , HTR5BP , HTR6 , HTR7 , CHRM1 , CHRM2 , CHRM3 , CHRM4, CHRM5 , ADORA1 , ADORA2A , ADORA2B , ADORA3 , ADRA1A , ADRA1B , ADRA1D , ADRA2A, ADRA2B , ADRA2C , ADRB1 , ADRB2 , ADRB3 , AGTR1 , AGTR2 , APLNR , GPBAR1 , NMBR, GRPR , BRS3 , BDKRB1 , BDKRB2 , CNR1 , CNR2 , CCR1 , CCR2 , CCR3 , CCR4 , CCR5 , CCR6, CCR7 , CCR8 , CCR9 , CCR10 , CXCR1 , CXCR2 , CXCR3 , CXCR4 , CXCR5 , CXCR6 , CXCR7, CX3CR1 , XCR1 , CCKAR , CCKBR , C3AR1 , C5AR1 , GPR77 , DRD1 , DRD2 , DRD3 , DRD4, DRD5 , EDNRA , EDNRB , GPER , FPR1 , FPR2 , FPR3 , FFAR1 , FFAR2 , FFAR3 , GPR42 , GALR1, GALR2 , GALR3 , GHSR , FSHR , LHCGR , TSHR , GNRHR , GNRHR2 , HRH1 , HRH2 , HRH3, HRH4 , HCAR1 , HCAR2 , HCAR3 , KISS1R , LTB4R , LTB4R2 , CYSLTR1 , CYSLTR2 , OXER1, FPR2 , LPAR1 , LPAR2 , LPAR3 , LPAR4 , LPAR5 , S1PR1 , S1PR2 , S1PR3 , S1PR4 , S1PR5, MCHR1 , MCHR2 , MC1R , MC2R , MC3R , MC4R , MC5R , MTNR1A , MTNR1B , MLNR , NMUR1, NMUR2 , NPFFR1 , NPFFR2 , NPSR1 , NPBWR1 , NPBWR2 , NPY1R , NPY2R , PPYR1 , NPY5R, NPY6R , NTSR1 , NTSR2 , OPRD1 , OPRK1 , OPRM1 , OPRL1 , HCRTR1 , HCRTR2 , P2RY1, P2RY2 , P2RY4 , P2RY6 , P2RY11 , P2RY12 , P2RY13 , P2RY14 , QRFPR , PTAFR , PROKR1, PROKR2 , PRLHR , PTGDR , PTGDR2 , PTGER1 , PTGER2 , PTGER3 , PTGER4 , PTGFR , PTGIR, TBXA2R , F2R, F2RL1, F2RL2, F2RL3, RXFP1 , RXFP2 , RXFP3 , RXFP4 , SSTR1 , SSTR2, SSTR3 , SSTR4 , SSTR5 , TACR1 , TACR2 , TACR3 , TRHR , TAAR1 , UTS2R , AVPR1A , AVPR1B, AVPR2 , OXTR , CCRL2 , CMKLR1 , GPR1 , GPR3 , GPR4 , GPR6 , GPR12 , GPR15 , GPR17, GPR18 , GPR19 , GPR20 , GPR21 , GPR22 , GPR25 , GPR26 , GPR27 , GPR31 , GPR32 , GPR33, GPR34 , GPR35 , GPR37 , GPR37L1 , GPR39 , GPR42 , GPR45 , GPR50 , GPR52 , GPR55, GPR61 , GPR62 , GPR63 , GPR65 , GPR68 , GPR75 , GPR78 , GPR79 , GPR82 , GPR83 , GPR84, GPR85 , GPR87 , GPR88 , GPR101 , GPR119 , O3FAR1 , GPR132 , GPR135 , GPR139 , GPR141, GPR142 , GPR146 , GPR148 , GPR149 , GPR150 , GPR151 , GPR152 , GPR153 , GPR160, GPR161 , GPR162 , GPR171 , GPR173 , GPR174 , GPR176 , GPR182 , GPR183 , LGR4 , LGR5, LGR6 , LPAR6 , MAS1 , MAS1L , MRGPRD , MRGPRE , MRGPRF , MRGPRG , MRGPRX1 , MRGPRX2, MRGPRX3 , MRGPRX4 , OPN3 , OPN5 , OXGR1 , P2RY8 , P2RY10 , SUCNR1 , TAAR2 , TAAR3, TAAR4P , TAAR5 , TAAR6 , TAAR8 , TAAR9 , CCBP2 , CCRL1 , DARC , CALCR , CALCRL , CRHR1, CRHR2 , GHRHR , GIPR , GLP1R , GLP2R , GCGR , SCTR , PTH1R , PTH2R , ADCYAP1R1 , VIPR1, VIPR2 , BAI1 , BAI2 , BAI3 , CD97 , CELSR1 , CELSR2 , CELSR3 , ELTD1 , EMR1 , EMR2, EMR3 , EMR4P , GPR56 , GPR64 , GPR97 , GPR98 , GPR110 , GPR111 , GPR112 , GPR113, GPR114 , GPR115 , GPR116 , GPR123 , GPR124 , GPR125 , GPR126 , GPR128 , GPR133, GPR144 , GPR157 , LPHN1 , LPHN2 , LPHN3 , CASR , GPRC6A , GABBR1 , GABBR2 , GRM1, GRM2 , GRM3 , GRM4 , GRM5 , GRM6 , GRM7 , GRM8 , GPR156 , GPR158 , GPR179 , GPRC5A, GPRC5B , GPRC5C , GPRC5D , TAS1R1 , TAS1R2 , TAS1R3 , FZD1 , FZD2 , FZD3 , FZD4, FZD5 , FZD6 , FZD7 , FZD8 , FZD9 , FZD10 , SMO , GPR107 , GPR137 , OR51E1 , TPRA1, GPR143 , THRA , THRB , RARA , RARB , RARG , PPARA , PPARD , PPARG , NR1D1 , NR1D2, RORA , RORB , RORC , NR1H4 , NR1H5P , NR1H3 , NR1H2 , VDR , NR1I2 , NR1I3 , HNF4A, HNF4G , RXRA , RXRB , RXRG , NR2C1 , NR2C2 , NR2E1 , NR2E3 , NR2F1 , NR2F2 , NR2F6, ESR1 , ESR2 , ESRRA , ESRRB , ESRRG , AR , NR3C1 , NR3C2 , PGR , NR4A1 , NR4A2 , NR4A3, NR5A1 , NR5A2 , NR6A1 , NR0B1 , NR0B2 , HTR3A , HTR3B , HTR3C , HTR3D , HTR3E , GABRA1, GABRA2 , GABRA3 , GABRA4 , GABRA5 , GABRA6 , GABRB1 , GABRB2 , GABRB3 , GABRG1, GABRG2 , GABRG3 , GABRD , GABRE , GABRQ , GABRP , GABRR1 , GABRR2 , GABRR3 , GLRA1, GLRA2 , GLRA3 , GLRA4 , GLRB , GRIA1 , GRIA2 , GRIA3 , GRIA4 , GRID1 , GRID2 , GRIK1, GRIK2 , GRIK3 , GRIK4 , GRIK5 , GRIN1 , GRIN2A , GRIN2B , GRIN2C , GRIN2D , GRIN3A, GRIN3B , CHRNA1 , CHRNA2 , CHRNA3 , CHRNA4 , CHRNA5 , CHRNA6 , CHRNA7 , CHRNA9, CHRNA10 , CHRNB1 , CHRNB2 , CHRNB3 , CHRNB4 , CHRNG , CHRND , CHRNE , P2RX1 , P2RX2, P2RX3 , P2RX4 , P2RX5 , P2RX6 , P2RX7 , ZACN , AGER , TLR1 , TLR2 , TLR3 , TLR4 , TLR5, TLR6 , TLR7 , TLR8 , TLR9 , TLR10 , TLR11 , LILRA1 , LILRA2 , LILRA3 , LILRA4 , LILRA5, LILRA6 , LILRB1 , LILRB2 , LILRB3a , LILRB4 , LILRB5 , LILRB6 , LILRB7 , EGFR, ERBB2 , ERBB3 , ERBB4 , GFRa1 , GFRa2 , GFRa3 , GFRa4 , NPR1 , NPR2 , NPR3 , NPR4, NGFR , NTRK1 , NTRK2 , NTRK3 , EGFR , ERB2 , ERB3 , ERB4 , INSR , IRR , IG1R , PDGFalpha, PDGFbeta , Fms , Kit , Flt3 , FGFR1 , FGFR2 , FGFR3 , FGFR4 , BFR2 , VGR1 , VGR2, VGR3 , EPA1 , EPA2 , EPA3 , EPA4 , EPA5 , EPA7 , EPA8 , EPB1 , EPB2 , EPB3 , EPB4 , EPB6, TrkA , TrkB , TrkC , UFO , TYRO3 , MERK , TIE1 , TIE2 , RON , MET , DDR1 , DDR2 , RET, ROS , LTK , ROR1 , ROR2 , RYK , PTK7 , 및 KIT.
또한 수용체는 하기를 인식하는(recognizing) 인간 수용체로 고려된다; 인터류킨(interleukin) (IL)-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, IL-21, IL-22, IL-23, IL-24, IL-25, IL-26, IL-27, IL-28, IL-29, IL-30, IL-31, IL-32, IL-33, IL-34, IL-35, IL-36, IL-37, IL-38, 렙틴(leptin), 인터페론-알파(interferon-alpha), 인터페론-베타(interferon-beta), 인터페론-감마(interferon-gamma), 종양 괴사 인자 알파(tumor necrosis factor alpha), 림포톡신(lymphotoxin), 프로락틴(prolactin), 온코스타틴 M(oncostatin M), 백혈병 억제 인자(leukemia inhibitory factor), 집락촉진인자(colony-stimulating factor), 면역글로불린 A(immunoglobulin A), 면역글로불린 D(immunoglobulin D), 면역글로불린 G(immunoglobulin G), 면역글로불린 M(immunoglobulin M), 면역글로불린 E(immunoglobulin E), 인간 백혈구 항원(human leukocyte antigen)(HLA) A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G, HLA-DP, HLA-DQ, HLA-DR, 형질 전환 성장 인자 알파 (transforming growth factor alpha), 형질 전환 성장 인자 베타(transforming growth factor beta), 신경 성장 인자(nerve growth factor), 뇌 유도 신경 영양 인자(brain-derived neurotrophic factor), 뉴로트로핀-3(neurotrophin-3), 뉴로트로핀-4(neurotrophin-4), 아드레노메둘린(adrenomedullin), 안지오포이에틴 (angiopoietin), 자가분비 운동성 인자(autocrine motility factor), 뼈 형성 단백질(bone morphogenetic proteins), 에리스로포이에틴(erythropoietin), 섬유아세포성장촉진인자(fibroblast growth factor), 신경 아교 세포계 유도 신경 영양 인자(glial cell line-derived neurotrophic factor), 과립구집락자극인자(granulocyte colony-stimulating factor), 과립구 대식세포 콜로니 자극 인자 (granulocyte macrophage colony-stimulating factor), 성장 분화 인자-9(growth differentiation factor-9), 간세포 성장 인자(hepatocyte growth factor), 간종양-유래 성장 인자(hepatoma-derived growth factor), 인슐린 유사 성장 인자(insulin-like growth factor), 인슐린(insulin), 전이-자극 인자(migration-stimulating factor), 미오스타틴(myostatin), 혈소판-유래 성장 인자(platelet-derived growth factor), 트롬보포이에틴(thrombopoietin), 혈관 표피 성장 인자(vascular endothelial growth factor), 태반 성장 인자(placental growth factor), 결합조직 성장 인자(connective tissue growth factor), 및 성장 호르몬(growth hormone).
또한, 상동의(homologous) 비-인간(non-human) 유전자에 의해 암호화되는 수용체도 고려되며, 예로, 돼지(porcine), 말(equine), 소(bovine), 고양이(feline), 개(canine), 또는 쥐(murine)의 유전자; 및 동종의 식물 수용체 유전자에 의해 암호화되는 수용체, 예를 들어 밀(wheat), 보리(barley), 옥수수(corn), 쌀(rice), 호밀(rye), 귀리(oat), 콩(soybean), 땅콩(peanut), 해바라기(sunflower), 홍화(safflower), 아마(flax), 콩(beans), 담배(tobacco), 또는 생명 주식 공급 잔디(life-stock feed grasses)와 같은 농작물에서 발견되는 유전자, 및 사과, 배, 바나나, 감귤류 과일, 포도 등의 과일 식물에서 발견되는 유전자이다.
대부분의 다른 세포 수용체와 달리 멤브레인-접착(membrane-anchored) 및 멤브레인-스패닝(membrane-spanning) 단백질을 포함 또는 구성, 핵 수용체는 하나의 폴리펩타이드(polypeptide)에서 리간드 결합(ligand binding) 및 전사 인자 활성(transcription factor activity)을 결합시키는 수용성(soluble) 단백질이다. 핵 수용체는 사이토졸(cytosol) 또는 핵원형질(nucleoplasm)의 둘 중 한군데 위치하고, 이들은 리간드 결합에 의해 활성화되며, 이량화(dimerize) 및 전사 프로그램(transcriptional programs)의 수많은 배열(array)의 결과인 전사 인자가 활성화 된다. 상기 언급한 멤브레인-접착(membrane-anchored) 수용체와 달리, 세포 밖에서 그들 리간드의 결합 및 세포 내로 플라즈마 메브레인(plasma membrane)을 통한 신호의 변환(transduce), 지방 친화성(lipophilic) 리간드와 핵 수용체의 결합은 그들과 관련 있는 수용체로 접근을 얻고자 플라스마 멤브레인을 통할 수 있다. 게다가, 대부분의 수용체는 의도하는 세포의 결과를 달성하기 전에 복잡한 신호 증폭(amplification) 메카니즘에 의존한다. 다른 한편으로, 핵 수용체(Nuclear receptors)는 세포 반응에 리간드 결합을 직접적으로 변환한다(convert).
많은 질환의 치료는 핵 수용체 신효의 조절에 기초한다. 예를 들어, 염증 과정에서 글루코코르티코이드(glucocorticoids)는 글로코코르티코스테로이드 수용체(glucocorticosteriod receptor)를 활성화 시키고, 전립선 압(prostate cancer)에서는 안드로겐(androgen) 수용체의 안타고니스트(antagonists)는 유익한 치료 효과를 갖고, 또는 유방암에서 에스트로겐(estrogen) 수용체 신호를 차단하는 것은 유용하다. 전통적으로, 핵 수용체 아고니스트(agonist) 또는 안타고니스트(antagonists) 형태의 작은 분자는 치료 목적으로 수용체 신호에 영향을 주기 위해 사용된다. 그러나, 핵 수용체 신호는 핵 수용체 단백질 발현의 직접적 조절에 의해 영향받을 수 있으며, 이러한 조절은 본 발명의 대상이 될 수 있다.
본 발명에서 고려되는 핵 수용체는 하기의 인간 유전자에 의해 인간 핵 수용체로 암호화된다; AR , ESR1 , ESR2 , ESRRA , ESRRB , ESRRG , HNF4A , HNF4G , NR0B1 , NR0B2, NR1D1 , NR1D2 , NR1H2 , NR1H3 , NR1H4 , NR1I2 , NR1I3 , NR2C1 , NR2C2 , NR2E1 , NR2E3, NR2F1 , NR2F2 , NR2F6 , NR3C1 , NR3C2 , NR4A1 , NR4A2 , NR4A3 , NR5A1 , NR5A2 , NR6A1, PGR , PPARA , PPARD , PPARG , RARA , RARB , RARG , RORA , RORB , RORC , RXRA , RXRB, RXRG , THRA , THRB 및 VDR.
또한, 비-인간 핵 수용체는 언급된 인간 핵 수용체 유전자와 연관된 유전자에 의해 암호화 되며, 예를 들어, 돼지(porcine), 말(equine), 소(bovine), 고양이(feline), 개(canine), 또는 쥐(murine)의 전사인자이다.
유전자 프로모터의 단상부족(haploinsufficiency)에 의한 유전적 질병을 위해, 예를 들어, 성장 지체(growth retardation)를 유발하는 인슐린-유사 성장 인자 1 수용체(insulin-like growth factor I receptor) 단상부족(haploinsufficiency)또는 지배적 시신경 위축을 유발하는 OPA1 단상부족(haploinsufficiency), 뿐만 아니라, 남아있는 기능적 유전자 카피의 추가적인 기능이 환자에게 유익할 수 있다. 본 발명의 인공 전사 인자는 단상부족성(haploinsufficient) 유전자 프로모터로 부터 발현을 증가시킬 수 있고, 따라서 단상부족(haploinsufficiency)과 관련된 질병의 치료에 적합하다.
본 발명의 고려되는 하기 인간 유전자 및 이들 각각의 프로모터는 단상부족(haploinsufficiency)과 연관이 있고, 본 발명의 인공 전사 인자를 사용한 치료를 받아들일 수 있는 질병이다: PRKAR1A , FBN1 , ELN , TCOF1 , ENG , GLI3 , TCF4 , GRN, NKX2 -1, SOX10 , SHOX , MC4R , GATA3 , NKX2 -5, TBX1 , COL10A1 , PAX6 , LMX1B , BMPR2, PAX9 , SOX9 , TRPV4 , SPAST , TBX5 , TWIST1 , EHMT1 , FOXC2 , TBX3 , TNXB , DSP , OPA1, TRPS1 , RUNX2 , SCN1A , HOXD13 , NSD1 , SATB2 , PRPF31 , SOX2 , COL6A1 , APC , RAI1, PAX3 , ZEB2 , SLC40A1 , AFG3L2 , KCNQ2 , SALL1 , PPARG , GDF5 , GCH1 , MYH9 , SALL4, PITX2 , FOXF1 , RAD51 , PKD2 , NFKBIA , MSX1 , MSX2 , COL3A1 , SH3TC2 , SBDS , SIX6, KRIT1 , SLC33A1 , PARK2 , ABCA4 , MYOC , PAFAH1B1 , CDKN1C , CREBBP , FGF3 , MYF6, MPZ , ITPR1 , EDN3 , C3 , TYRP1 , OFC12 , ATM , FOXP2 , PHOX2B , COCH , PITX1 , EYA1, FOXC1 , KLF1 , GATA4 , KIT , MYCN , COL5A1 , RNF135 , MIR146A , SI , NLRP12 , NDUFA13, SPRED1 , REEP1 , SLC6A19 , CHD7 , NCF1 , IRF6 , RXFP2 , ZMPSTE24 , ATL1 , EGLN1, NLRP3 , KIF1B , BCMO1 , SLC6A20 , FOXL2 , RTN4R , TSC1 , WWOX , POLG2 , LGI1 , RECQL3, CNTNAP2 , ATP2C1 , KCNQ4 , RPS19 , ABCC6 , STXBP1 , NBN , ROBO1 , ROR2 , AGRP , STK11, KCNJ10 , LHX4 , FGF10 , LIG4 , ACVRL1 , CAV3 , GDF6 , SMAD4 , MYBPC3 , IRS2 , MSH6, ABCC8 , GARS , CDKN2A , PORCN , PHEX , ARX , DMD , TPM1 , NOTCH1 , ABL1 , RYR1 , PTH1R, PAX8 , PAX2 , BRAF , MAPT , MC3R , KCNH2 , LMNA , KRT5 , SOD1 , IGF1 , MNX1 , HNF1A, SLC2A1 , GCK , GABRG2 , FUS , DSG2 , DCC , OFC1 , CHRNA4 , BRCA1 , BDNF , BMP2 , ATP2A2, ALX4 , MITF , SIX3 , SMARCB1 , RANBP2 , GDNF , MYC , ATP1A2 , SLC6A4 , FOXG1 , IGF1R, FGFR1 및 SERPINA6.
또한, 고려되는 비-인간 유전자, 예를 들어, 돼지, 말, 소, 고양이, 개, 또는 쥐 유전자뿐만 아니라, 그들의 동종 인간 유전자, 식물 유전자, 예를 들어, 밀, 보리, 옥수수, 쌀, 호밀, 귀리, 콩, 땅콩, 해바라기, 홍화, 아마, 콩, 담배, 또는 생명 주식 공급 잔디(life-stock feed grasses)와 같은 농작물에서 발견되는 유전자, 및 사과, 배, 바나나, 감귤류 과일, 포도 등의 과일 식물에서 발견되는 유전자, 단상부족성(haploinsufficient) 프로모터(promoter)의 조절 아래있는 유전자이다.
인공 전사 유전자는 유전자 발현 조절에 유용하고, 따라서, 유전자 발현을 조절하는 질병의 치료에 유용하다. 종래의 약(drugs)이 특정 단백질의 활성을 조절하는 반면, 예를 들어, 아코니스틱(agonistic) 또는 안타고니스틱(antagonistic) 활성에 의해, 인공 전산 인자는 유전자 발현의 증가 또는 감소에 의해 이러한 단백질의 가용성(availability)을 변경시킨다.
전통적인 소분자(small molecule) 접근 방식으로, 단백질 활성의 조절을 통해 작용하는 치료적 활성의 소분자의 규명은 대부분 다른 분류의 물질(substances)로부터 다른 다양한 다른 분자 사이의 광범위하고, 시간-소모적인 스크리닝 절차에 의존하고, 소분자에 의한 유전자 발현의 조절은 가능하지 않았다. 대조적으로, 본 발명의 인공 전사인자는 매우 한정된 전체 조성물과 같은 물질 분류에 속해 있다. 두개의 매우 다양한 프로모터 서열을 표적하는 인공 전사 인자에 기초한 2개의 헥사머릭(hexameric) 아연 집게(zinc finger) 단백질은 전체적으로 유사한 4차 구조(tertiary structure)의 최소 아미노산 서열 동일성 85%를 갖고, 표준화된 방법(후술하는 바와 같이)을 통해 빠르고 경제적인 방법으로 발생(generated)할 수 있다. 따라서, 본 발명의 인공 전사 인자(artificial transcription factors)는 특별히 전체적으로 작은 조성에서 매우 넓고 다양한 표적 세트에 높은 특이성으로 분자의 한 분류에서 결합할 수 있다. 모든 생물에 대해서, 항-약물 항체로 부터의 면역 반응 및 이와 관련된 면역 반응이 고려된다. 그러나, 아연 집게(zinc finger) 모듈의 높은 보존성 때문에, 이러한 면역 반응은 본 발명의 인공 전사 인자의 적용에 의해 최소화 또는 부재되며, 또는 고정된 표적 부위 결합 및 기능이 제거된 면역원성(immunogenicity)의 전체적 구조의 작은 변화에 의해 제거되거나 최소화될 수 있다. 게다가, 폴리에틸렌 글리콜(polyethylene glycol)을 이용한 본 발명의 인공 전사 인자의 조절은 면역원성(immunogenicity)을 감소시키는 것으로 간주된다.
인공 전사 인자는 특이적 유전자의 프로모터 위치(regions)에 특이적으로 작용하기 위해 맞춤되기 때문에, 인공 전사 인자의 이용은 근접하게 관련 단백질이 있어도 선택적으로 표적할 수 있다. 이것은 근접하게 관련 단백질이 있어도 프로모터 위치의 느슨한 보존(loose conservation)에 기초한다. 본 발명에 따른 인공 전사 인자의 높은 선택성의 장점은, 비록 약물 작용의 조직-특이적 표적이어도 인공 전사 인자를 이용하여 개별적으로 지정된 단백질 패밀리의 특정 멤버 발현의 조직-특이적 발현에 종종 기초할 수 있다. 또한, 약물로 인공 전사 인자의 제형은 약물 개발 과정에 처리된 이전의 경험에 의해 의존할 수 있다.
그러나, 인공 전사 인자는 유전자 발현의 조절을 통해 효과적으로 작용하기 위해 세포의 핵 구획으로 존재할 필요가 있다. 지금까지, 인공 전사 인자의 치료적 전달을 위한 선택은 형질 전환을 통한 플라스미드 DNA의 형태 또는 바이러스 벡터(viral vectors)를 이용한 형태 중 하나이다. 치료 목적의 플라스미드 형질 전환은 낮은 효율을 갖고, 반면에 바이러스 벡터는 특이적으로 면역원성의 높은 잠재력(potential)을 갖으며, 따라서 어떠한 치료의 적용에 반복되기에 그들은 한계를 갖고 있다. 따라서, 인공 전사 인자 전달의 모드, 예를 들어, 핵산 대신 단백질 형태가 요구된다.
단백질 전달 도메인(Protein transduction domain, PTD)이 매개된 세포 내 인공 전사 인자의 전달은 새로운 방식의 인공 전사 인자의 높은 선택성 및 다양성의 장점을 갖는 새로운 방법이다. 단백질 전달 도메인은 플라스마 멤브레인 장벽(plasma membrane barrier)을 투과하고, 세포 안으로 카고 단백질을 수송할 수 있는 작은 펩타이드(peptides)이다. 이러한 단백질 전달 도메인은, 예를 들어 HIV 유래된 TAT 펩타이드, mT02, mT03, R9, ANTP, 및 기타 등이 있다. 세포내 흡수의 모드는 식균 작용(endocytosis)과 같고, 이는 TAT 펩타이드가 카고 단백질을 퓨전할 때, 세포-유형 독립적인 대식세포음작용(macropinocytotic) 흡수를 유도할 수 있는 것을 나타낸다(Wadia J.S. et al ., 2004, Nat Med 10, 310-315). 세포막의 장벽을 횡단하고 엔도솜 소체로 흡수하여 세포를 입력하는 첫 단계 동안, 엔도솜 구획의 내부는 세포의 외부와 동일하다. 따라서, 엔도솜 국지화(localization)는 세포질 또는 핵원형질(nucleoplasmic) 국지화와 동일하지 않다. 그러나, 엔도솜 구획의 약점 및/또는 멤브레인 무결성을 조절하는 관점에서 카고 또는 단백질 생산 도메인의 일부 본질적인 속성의 약점을 통해, 전달된 단백질은 엔도솜에서 벗어날 수 있으며 다른 진정한 세포 내 표적에 도달할 수 있다. 막 활성, 융해 펩티드 TAT-HA2 또는 GALA 또는 KALA 펩티드와 같은 다른 것의 공동 전달은 엔도솜 소포의 붕괴로 인해 전달된 단백질의 엔도솜 배출을 향상시킨다. 실제로, 엔도솜 막을 방해할 수 있는 메커니즘은 단백질 전달 도메인을 이용하여 전달된 화물 단백질의 엔도솜 배출을 증가시키는데 최신식이다.
그러나, 막 방해 제제는 예상대로 전달을 촉진하는데 효율적이지 않다. 이는 단백질 전달 도메인의 고유 특성 때문일 것이다. 단백질 전달 도메인은 세포 막과 강하게 상호작용하는 것으로 알려져 있다. 이러한 강한 막 상호작용은 어떤 단백질의 내재화 및 단백질 전달이 트리거되는 메커니즘의 일부이다. 따라서, 에노좀으로 내재화한 후, 엔도솜 막 내부에 있는 이러한 단백질 전달 도메인의 강한 막 상호작용은 엔도솜 소포체의 파열 후 재분배를 억제할 수 있다. TAT 융합 인공 전사 인자는 주로 일부 핵 국부화를 가지는 엔도솜 구획에서 주로 상주할 수 있다. 흥미롭게도, TAT 인공 전사 인자로 염색된 세포의 큰 비율에서, 파열된 엔도솜 소포체는 엔도솜 막 파열 후 전달된 단백질의 상당한 양의 엔도솜 포획과 일치하는, TAT 융합 단백질로 명확하게 장식된 엔도솜 멤브레인을 가진 세포질에 개방이 발견되었다. 따라서, 세포 내로 흡수에 필수적인 반면 단백질 전달 도메인은 효과적인 세포 내 위치 파악을 방해한다.
엔도좀은 성숙하고 프로테아제를 취득하고 엔도좀 콘텐츠의 리소좀 구획 및 단백질 분해 열화 소포 융합 전에 pH의 저하를 나타내는 같은 리소좀 특성을 취득하는 것으로 알려진 매우 동적인 소기관이다. 이러한 단백질은 단백질 분해효소를 대상으로 하기 때문에, 내강 단백질 분해 활성의 증가를 수반한 엔도좀 숙성 공정은 단백질 전달 도메인을 사용하여 전달된 치료적 단백질에 해롭다. 그러나, 이러한 공정은 이점으로 전환될 수 있다. 엔도솜 성숙은 순차적인 공정이며 여기서 프로테아제는 상이한 세트는 pH 의존적으로 여러 단계에서 활성화된다. 흥미롭게도, 단백질 처리에 참여하는 공정에서 초기 활성화된 프로테아제는 단백질의 일반적인 가수분해 효소에 필수적인 성숙하는 동안 활성화된 프로테아제 보다 더 특이적 서열이다. 단백질 전달 도메인 및 화물 단백질 간의 초기 엔도솜 프로테아제를 위한 절단 부위의 통합은 치료적 단백질이 엔도솜 루멘에 도달하면 화물 단백질로부터 단백질 전달 도메인으로 분리된 치료적 단백질의 서열 특이적 절단으로 이르게 한다. 따라서, 엔도솜 파단시 TAT 매개된 인공 전사 인자의 전달 후 자주 관찰되는, 화물 단백질은 단백질 전달 도메인의 고유 특성 때문에 더이상 엔도솜 막 내부에 결합하지 않으나, 세포질로 배출하기 위해 막으로부터 분리된다(도 1).
엔도솜 구획에서 프로테아제 활성은 pH 최적 및 서열 특이적 관점에서 상이한 특성을 가지는 다양한 프로테아제의 큰 패밀리인, 카텝신이다. 예를 들어, 카텝신 B는 약 중성의 최적 pH를 가지며 엔도솜 프로테아제를 처리하는 TAT-화물 융합 단백질로써 이러한 프로테아제가 좋은 선택임을 만들어주는 서열 특이적이다. 그러나, 카텝신 H, L, S, C, K, O, F, V, X, W, D 또는 E와 같은 다른 카텝신은 엔도솜 구획이 한번 도달하면 이들의 화물로부터 단백질 전달 도메인 분리의 목적을 위해 유용하게 사용될 수도 있다. 특정 카텝신의 조직 및 세포 타입 특이적 발현을 활용하는 것은, 향상된 세포 내 국지화 및 따라서 이러한 치료제의 효과적인 약학적 기능은 이러한 조직 또는 세포에 특이적인 카텝신 인식 부위를 포함함으로써 특정 세포 타입으로 제한될 수 있다.
인공 전사 인자와 같은 화물 단백질의 엔도솜 배출을 향상시키기 위해 본 발명에서, 카텝신 B 부위와 같은 프로테아제 인식 부위의 용도는 최첨단식이다. 공지된 방법과 달리, 추가적인 엔도솜 소포 파열은 도입되지 않으나, 화물 단백질은 소포체 파열 기준선 후 엔도솜으로부터 효율적으로 배출을 위해 허락된 엔도솜으로 진힙 후 단백질 전달 도메인으로부터 분리된다.
공지된 예에서, 세포 투과 펩티드는 단백질 전달의 선택성을 증가시키는 목적으로, 프로테아제 인식 부위와 함께 사용될 수 있다(EP 2 399 939, WO 2008/063113). 억제 펩티드와 함께 단백질 전달 도메인을 마스킹 함으로써, 세포막에 걸친 화물 수송은 방지된다. 조직 및/또는 세포 타입 특이적 세포 외 프로테아제가 발생하면, 이러한 억제 펩티드는 세포막 단백질을 가로질러 단백질 수송을 위해 절단된다. 이러한 최첨단 예는 본 발명에 기재된 엔도솜 배출 증가로 이어지는 특정한 구조로부터 실질적으로 상이하다.
다른 공지된 예에서, 엔도솜 프로테아제 인식 부위는 단백질 전달 도메인(WO 2005/003315)과 함께 사용된다. 이때, 상기 제공된 절차는 세포 내로 DNA의 수송 방법이다. 상기 엔도솜 프로테어제 부위는 오직 엔도솜 루트를 통한 DNA 복합체의 전체를 확인하기 위한 마커로써 사용되며, DNA의 엔도솜 배출 향상을 위한 것이 아니다.
마커로써 엔도솜 프로테아제 인식 부위의 용도를 설명하는 반면에, 본 발명의 구조체는 기능 단백질의 증가된 엔도솜 배출을 제공하며, DNA 복합체의 전체 루트의 결실을 위한 마커가 아니다.
또한, 본 발명의 인공 전사 인자는 핵 국소화 서열(nuclear localization sequence; NLS)를 포함한다. 핵 국소화 서열은, 예를 들어 라이신(K) 또는 아르기닌(R) 잔기, 임의의 아미노산(X), 라이신 또는 아기닌 잔기(K-K/R-X-K/R consensus sequence, Chelsky D. et al., 1989 Mol Cell Biol 9, 2487-2492) 또는 SV40 NLS (서열번호 37), 바람직하게는 SV40 NLS 다음의 라이신 잔기(K)를 포함하는 염기성 아미노산의 클러스터인, 유전자 오톨로지 GO:0008139에 의해 정의된 단백질에 결합을 통해 핵 도출을 부여한 아미노산 모티프로 여겨진다.
본 발명의 인공 전사 인자는 또한 N-말단 KRAB, C-말단 KRAB, SID 및 ERD 도메인, 바람직하게는 KRAB 또는 SID와 같은, 유전자 오톨로지 GO:0001071에 의해 정의된 단백질의 다른 전사적으로 활성적인 단백질 도메인을 포함한다. 고려되는 활성적인 단백질 도메인은 VP16, VP64 (VP16의 4량 반복), CJ7, p65-TA1, SAD, NF-1, AP-2, SP1-A, SP1-B, Oct-1, Oct-2, Oct2-5x, MTF-1, BTEB-2, 및 LKLF, 바람직하게는 VP64 및 AP-2와 같은 유전자 오톨로지 GO:0001071에 의해 정의된 단백질의 전사적으로 활성적인 도메인이다.
본 발명의 인공 전사 인자로 고려되는 것은 5량체, 6량체, 7량체 또는 8량체 아연 집게 단백질이며 여기서 개별적 아연 집게 모듈은 개별적인 핵 수용체 프로모터 유전자의 표적 위치에 대한 결합 친화도를 향상시키기 위해 또는 내약성을 개선하기 위한 아연 집게 단백질의 면역학적 프로파일을 변경하기 위해 교환되었다.
본 발명의 인공 전사 인자의 도메인은 짧은 유연성 링커에 의해 연결될 수 있다. 짧은 유연성 링커는 2 내지 8 아미노산을 가지며, 바람직하게는 글라이신 및 세린이다. 구체적인 링커는 GGSGGS (서열번호 38)로 고려된다. 인공 전사 인자는 추가적으로 에피토프 태그와 같은 이들의 결실 또는 처리를 용이하게 하기 위한 마커를 포함할 수 있다.
TAT-HA2, GALA 또는 KALA와 같은 융해성 펩티드의 공동 전달은 단백질 전달 후 화물 단백질의 엔도솜 배출을 증가시키는 것으로 나타났다. 그러나, 이러한 펩티드의 공동 배달은 생체 내에서 단백질 전달을 증가시키기 위해 살아있는 시스템에서 구성 요소에 대한 분포 및 제거 동작의 차이를 가지는, 융해 펩티드 및 치료 단백질과 같이 두 구획 시스템에서 알 수 있듯이, 가능한 옵션이 아니다.
치료적 단백질로 융해 펩티드의 통합은 상기 언급한 두 개의 구성 요소 문제를 회피하기 위해 더 나은 선택이다. 그러나, 이러한 융해 펩티드는 상호작용할 가능성에서 크기 측면의 일정한 한계를 가지며, N 뿐만 아니라 C 말단 아미노산 서열에서 엔도솜 막을 위한 융합생성(fusogen)으로써 작용한다. 따라서, 단순히 융해 펩티드를 화물 단백질로 통합하는 것은 엔도솜 배출을 증가시키기 위한 가능한 옵션이 아니다.
그러나 엔도솜 프로테아제 민감적 린커 영역을 통해 융해 펩티드를 본 발명의 인공 전사 인자로 통합하는 것은 엔도솜 루멥으로 화물 단백질 및 융해성 펩티드의 동시 전달을 허용한다. 엔도솜 내부에서, 단백질 전달 도메인으로부터 인공 전사 인자의 분리가 발생하며, 및 게다가 융해성 펩티드가 방출한다. 융해성 펩티드의 다중 반복의 봉입을 통해서, 엔도솜 프로테아제 부위, 다중 융해성 펩티드에 의해 각각의 융해성 펩티드 아단위의 분리가 엔도솜으로 전달되어 엔도솜 파열을 증가시킨다.
주어진 프로모터 영역 내에서 표적 부위의 선택
표적 부위 선택은 기능적 인공 전사 인자의 성공적인 생성을 위해 매우 중요하다. 생체 내에서 표적 유전자 발현을 조절하기 위한 인공 전사 인자를 위해, 표적 유전자의 게놈 관련에서 표적 부위에 결합한다. 이는 이 부위에서 염색체 DNA가 뉴클레오좀으로 히스톤 주위에 단단히 포장되지 않고, 인공 전사 인자 결합과 함께 메틸화 방해와 같은 DNA 수정이 아님을 의미하는, DNA 표적 부위의 접근을 필요로 한다. 인간 게놈의 큰 부분이 단단히 포장되고 전사적으로 비활성화하는 반면, 활성적인 전사 유전자의 전사 시작 부위(-1000 to +200 bp)의 바로 근처는 RNA 중합효소와 같은 내재적 전사 인자 및 전사 기계에 대한 접근이 가능해야 한다. 따라서, 임의의 주어진 표적 유전자의 영역에서 표적 부위의 선택은 생체 내에서 원하는 기능을 가진 인공 전사 인자의 생성에 대한 성공률을 향상시킬 것이다.
인간 엔도텔린 수용체 A( ETRA ) 프로모터 영역 내의 표적 부위의 선택
인간 ETRA 유전자의 프로모터 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 세 표적 부위는 전사 개시 위치에 상대적인 이들의 위치에 기초하여 선택되며 ETRA_TS-37 (서열번호 39), ETRA_TS-50 (서열번호 40) 및 ETRA_TS+74 (서열번호 41)로 지정되었다. 또한 전사 개시의 상부 2000 bp ETRA 유전자의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
인간 엔도텔린 수용체 B( ETRB ) 프로모터 영역 내의 표적 부위의 선택
인간 ETRB 유전자의 프로모터 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 두 표적 부위는 전사 개시 위치에 상대적인 이들의 위치에 기초하여 선택되며 ETRB_TS-1149 (서열번호 42) 및 ETRB_TS-487 (서열번호 43)로 지정되었다. 또한 전사 개시의 상부 2000 bp ETRB 유전자의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
인간 Toll -유사 수용체 4 ( TLR4 ) 프로모터 영역 내의 표적 부위의 선택
인간 TLR4 유전자의 프로모터 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 두 표적 부위는 전사 개시 위치에 상대적인 이들의 위치에 기초하여 선택되며 TLR4_TS-55 (서열번호 44), TLR4_TS-222 (서열번호 45) 및 TLR4_TS-276 (서열번호 46)로 지정되었다. 또한 전사 개시의 상부 2000 bp TLR4 유전자의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
인간 높은 친화성 IgE 수용체 A( FCER1A ) 프로모터 영역 내의 표적 부위의 선택
인간 FCER1A 유전자의 전사 개시 영역을 포함하는 프로모터 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 두 표적 부위는 전사 개시 위치에 상대적인 이들의 위치에 기초하여 선택되며 IgER_TS-147 (서열번호 47) 및 IgER_TS17 (서열번호 48)로 지정되었다. 또한 전사 개시의 상부 2000 bp FCER1A 유전자의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
인간 TGFbR1 유전자 내의 표적 부위의 선택
인간 TGFbR1 유전자의 전사 개시 영역을 포함하는 프로모터 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 하나의 표적 부위는 전사 개시 위치에 상대적인 이들의 위치에 기초하여 선택되며 TGF_TS-390 (서열번호 49)로 지정되었다. 또한 전사 개시의 상부 2000 bp TGFbR1 유전자의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
인간 글루코코르티코이드( glucocorticoid ), 안드로겐( androgen ) 및 에스트로겐(estrogen ) 수용체 유전자 프로모터 내의 표적 부위의 선택
인간 글루코코르티코이드, 안드로겐 및 에스트로겐 수용체 유전자의 전사 개시 영역 1000 bp를 포함하는 프로모터 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 각 프로모터에서 셋 내지 네 개의 표적 부위는 전사 개시 위치에 상대적인 이들의 위치에 기초하여 선택된다. 글루코코르티코이드 수용체 유전자 프로모터에서 발견된 표적 부위는 GR_TS1 (서열번호 50), GR_TS2 (서열번호 51), GR_TS3 (서열번호 52), 안드로겐 수용체의 표적 부위는 AR_TS1 (서열번호 53), AR_TS2 (서열번호 54), AR_TS3 (서열번호 55) 및 AR_TS-236 (서열번호 56)이다. 에스트로겐 수용체 유전자 프로모터에서 밝혀진 타겟 부위는 ER_TS1 (서열번호 57), ER_TS2 (서열번호 58) 및 ER_TS3 (서열번호 59)이다. 또한 전사 개시의 상부 2000 bp 글루코코르티코이드 수용체, 에스트로겐 수용체 및 안드로겐 수용체의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
인간 OPA1 유전자 프로모터 내의 표적 부위의 선택
인간 OPA1 오픈 리딩 프레임의 시작 코돈의 상부 1000 bp 영역은 (G/CANN)6의 일반적인 조성물을 가지는 잠재적 18 bp 표적 부위의 존재를 위해 분석되며, 여기서 G는 염기 구아닌(guanine), C는 염기 시토신(cytosine), A는 염기 아데닌(adenine) 및 N은 구아닌, 시토신, 아데닌 및 티민(thymine)의 네 염기 각각을 대표한다. 네 개의 표적 부위, OPA_TS1 (서열번호 60), OPA_TS2 (서열번호 61), OPA_TS3 (서열번호 62), 및 OPA_TS-165 (서열번호 63)가 선택되었다. 또한, 전사 개시의 상부 2000 bp OPA1 오픈 리딩 프레임의 조절 영역으로부터 선택된 (G/C/ANN)5 및 (G/C/ANN)6의 일반적 조성물의 표적 위치 또한 고려된다.
수용체 유전자 프로모터를 타겟으로 하는 인공 전사 인자
특이적 유전자 표적 부위를 표적으로 하는 육량체(Hexameric)의 아연 집게 단백질은 변형된 효모 하나의 하이브리드 스크린을 이용하여 선별하였다. 표적 부위 및 효모 cys1 최소 프로모터를 포함하는 키메라성 효모 프로모터의 대조군 하에 아우레오바시딘(aureobasidin) A 내성 유전자를 함유하는 효모는 GAL4 활성화 도메인에 융합된 육량체 아연 집게 단백질로 구성된 하이브리드 활성화 전사 인자를 위한 발현 플라스미드의 플라스미드 라이브러리로 형질전환되었다. 상기 언급된 키메라성 효소 프로모터에 하이브리드 전사 인자의 결합에 따라, 아우레오바시딘 A 내성 유전자는 육량체형 아연 집게 및 시험된 표적 부위 간의 상호작용의 상대적인 힘이 항생제에 대하여 전사되어 내성을 부여한다. 증가 압력을 이용하여, 특정 표적 부위에 강한 결합 친화도를 가지는 육량체 아연 집게 단백질이 선택되었다. 이러한 특이적으로 표적하는 아연 집게 단백질은 인공 전사 인자를 얻기 위해 전사 활성 도메인 VP64 또는 억제제 도메인 N-KRAB, C-KRAB 또는 SID 뿐만 아니라 단백질 전달 도메인 TAT에 결합한다. 카텝신 B 민감성 인공 전사 인자를 생성하기 위해, 카텝신 B 부위는 TAT 단백질 전달 도메인 및 핵 국소화 서열, 아연 집게 단백질 및 조절 도메인으로 구성된 인공 전사 인자 사이에서 유도된다.
ETRA 특이적 육량체 아연 집게(hexameric zinc fingers)는 ETRA-37B (서열번호 64), ETRA-37D (서열번호 65), ETRA-50A (서열번호 66), ETRA-50B (서열번호 67), ETRA-50C (서열번호 68), ETRA-50D (서열번호 69), ETRA-50E (서열번호 70), ETRA-50F (서열번호 71), ETRA-50G (서열번호 72), ETRA-50H (서열번호 73), ETRA-50I (서열번호 74), ETRA-50J (서열번호 75), ETRA-50K (서열번호 76), ETRA-50L (서열번호 77), ETRA-50M (서열번호 78),ETRA+74E (서열번호 79), ETRA+74V (서열번호 80), ETRA+74R (서열번호 81), ETRA+74AA (서열번호 82), ETRA+74AB (서열번호 83), ETRA+74AC (서열번호 84), ETRA+74AD (서열번호 85), ETRA+ 74AE (서열번호 86), ETRA+74AF (서열번호 87), ETRA+74AG (서열번호 88), 및 ETRA+74AH (서열번호 89)이다. 전사 인자를 포함하는 ETRA-특이적 카텝신 B 민감성 VP64- (akt) 또는 SID- (repS)의 결과는 ETRA+74Eakt (서열번호 90), ETRA+74ErepS (서열번호 91), ETRA+74Rakt (서열번호 92), ETRA+74RrepS (서열번호 93), ETRA+74Vakt (서열번호 94), ETRA+74VrepS (서열번호 95), ETRA+74AAakt (서열번호 96), ETRA+74AArepS (서열번호 97), ETRA+74ABakt (서열번호 98), ETRA+74ABrepS (서열번호 99), ETRA+74ACakt (서열번호100), ETRA+74ACrepS (서열번호 101), ETRA+74ADakt (서열번호 102), ETRA+ 74ADrepS (서열번호 103), ETRA+74AEakt (서열번호 104), ETRA+ 74AErepS (서열번호 105), ETRA+74AFakt (서열번호 106), ETRA+74AFrepS (서열번호 107), ETRA+74AGakt (서열번호 108), ETRA+74AGrepS (서열번호 109), ETRA+ 74AHakt (서열번호 110), ETRA+74AHrepS (서열번호 111), ETRA-37Bakt (서열번호 112), ETRA-37BrepS (서열번호 113), ETRA-37Dakt (서열번호 114), ETRA-37DrepS (서열번호 115), ETRA-50Aakt (서열번호 116), ETRA-50ArepS (서열번호 117), ETRA-50Bakt (서열번호 118), ETRA-50BrepS (서열번호 119), ETRA-50Cakt (서열번호 120), ETRA-50CrepS (서열번호 121), ETRA-50Dakt (서열번호 122), ETRA-50DrepS (서열번호 123), ETRA-50Eakt (서열번호 124), ETRA-50ErepS (서열번호 125), ETRA-50Fakt (서열번호 126), ETRA-50FrepS (서열번호 127), ETRA-50Gakt (서열번호 128), ETRA-50GrepS (서열번호 129), ETRA-50Hakt (서열번호 130), ETRA-50HrepS (서열번호 131), ETRA-50Iakt (서열번호 132), ETRA-50IrepS (서열번호 133), ETRA-50Jakt (서열번호 134), ETRA-50JrepS (서열번호 135), ETRA-50Kakt (서열번호 136), ETRA-50KrepS (서열번호 137), ETRA-50Lakt (서열번호 138), ETRA-50LrepS (서열번호 139), ETRA-50Makt (서열번호 140), 및 ETRA-50MrepS (서열번호 141)이다. 카텝신 B 비-민감성 인공 전사 인자는 ETRA+74VrepSNPS (서열번호 142)이다. 대조군 목적을 위해 시스테인 잔기로 조성된 모든 아연이 결여된 비활성 버전의 ETRA+74VrepS는 ETRA+74Vmut_repS (서열번호 143)이다.
ETRB-특이적 육량체 아연 집게는 ETRB-1149H (서열번호 144), ETRB-1149N (서열번호 145), ETRB-487C (서열번호 146), 및 ETRB-487E (서열번호 147)이다. 전사 인자를 포함하는 ETRB-특이적 카텝신 B 민감성 VP64- (akt) 또는 SID- (repS)의 결과는 ETRB-1149Hakt (서열번호 148), ETRB-1149HrepS (서열번호 149), ETRB-1149Nakt (서열번호 150), ETRB-1149NrepS (서열번호 151), ETRB-487Cakt (서열번호 152), ETRB-487CrepS (서열번호 153), ETRB-487Eakt (서열번호 154), 및 ETRB-487ErepS (서열번호 155)이다.
TLR4-특이적 육량체 아연 집게는 TLR4-55B (서열번호 156), TLR4-55E (서열번호 157), TLR4-222A (서열번호 158), TLR4-222B (서열번호 159), TLR4-276B (서열번호 160), and TLR4-276C (서열번호 161)이다. 전사 인자를 포함하는 TLR4 특이적 카텝신 B 민감적 VP64- (akt) 또는 SID- (repS)의 결과는 TLR4-55Bakt (서열번호 162), TLR4-55BrepS (서열번호 163), TLR4-55Eakt (서열번호 164), TLR4-55ErepS (서열번호 165), TLR4-222Aakt (서열번호 166), TLR4-222ArepS (서열번호 167), TLR4-222Bakt (서열번호 168), TLR4-222BrepS (서열번호 169), TLR4-276Bakt (서열번호 170), TLR4-276BrepS (서열번호 171), TLR4-276Cakt (서열번호 172), 및 TLR4-276CrepS (서열번호 173)이다.
FCER1A-특이적 육량체 아연 집게는 IgER-147A (서열번호 174), IgER-147G (서열번호 175), IgER+17G (서열번호 176), and IgER+17I (서열번호 177)이다. 전사 인자를 포함하는 FCER1A-특이적 카텝신 B 민감성 VP64- (akt) 또는 SID- (repS)의 결과는 IgER-147Aakt (서열번호 178), IgER-147ArepS (서열번호 179), IgER-147Gakt (서열번호 180), IgER-147GrepS (서열번호 181), IgER+17Gakt (서열번호 182), IgER+17GrepS (서열번호 183), IgER+17Iakt (서열번호 184), 및 IgER+17IrepS (서열번호 185)이다. 카텝신 B 비-민감적 인공 전사 인자는 IgER-147ArepSNPS (서열번호 186)이다. 대조군 목적으로써 시스테인 잔기를 구성하는 모든 아연이 결여된 IgER-147ArepS의 비활성 버전은 IgER-147Amut_repS (서열번호 187)이다.
TGFbR1-특이적 육량체 아연 집게 단백질은 TGF-390A (서열번호 188)이다. 전사 인자를 포함하는 TGFbR1-특이적 카텝신 B-민감성 VP64- (akt) 또는 SID- (repS)의 결과는 TGF-390Aakt (서열번호 189) 및 TGF-390repS (서열번호 190)이다.
다른 실시형태에서, 본 발명에 따른 특정 막 기초 수용체 유전자 프로모터를 표적하는 인공 전사 인자는 서열번호 64 내지 89, 144 내지 147, 156 내지 161, 174 내지 177, 및 188의 아연 집게 모듈 조성물에 기초한 아연 집게 단백질을 포함하며, 여기서 최대 셋, 바람직하게는 하나 또는 둘, 각각의 아연 집게 모듈은 표적 서열에 인공 전사 인자의 결합을 조절하기 위한 대안적인 결합 특성을 가지는 다른 아연 집게 모듈로 변환되고, 및/또는 여기서 최대 12, 가장 바람직하게는 하나 또는 두 개의 개별 아미노산이 의도된 표적 부위에 결합 친화도를 유지하는 동안 잠재적인 면역원성을 최소화하기 위해 변환된다.
구체적인 실시형태에서, 수용체 유전자 프로모터를 표적화하는 인공 전사 인자는 서열번호 64 내지 89, 144 내지 147, 156 내지 161, 174 내지 177, 및 188의 아연 집게 모듈 조성물에 기초한 아연 집게 단백질을 포함하며, 여기서 선택적으로 최대 셋, 바람직하게는 하나 또는 둘, 개별적 아연 집게 모듈인 표적 서열에 인공 전사 인자의 결합을 조절하는 대안적인 결합 특성을 가지는 다른 아연 집게 모듈로 변환하며, 및/또는 여기서 선택적으로 최대 12, 가장 바람직하게는 하나 또는 두 개의 개별적 아미노산이 의도된 표적 부위에 결합 친화도를 유지하는 동안 잠재적 면역원성을 최소화하기 위해 변환되며, 및 여기서 전사 조절 도메인은 VP16, VP64, CJ7, p65-TA1, SAD, NF-1, AP-2, SP1-A, SP1-B, Oct-1, Oct-2, Oct2-5x, MTF-1, BTEB-2, LKLF, N-KRAB, C-KRAB, SID 또는 ERD이다. 보다 구체적으로, 본 발명은 엔조솜 특이적 부위가 카텝신 B 절단 부위인 인공 전사 인자, 및 엔도솜 특이적 부위가 잠재적 면역원성 또는 절단 특이성 또는 효율성을 최소화하기 위해 변경된 카텝신 B 절단 부위인 인공 전사 인자인 인공 전사 인자에 관한 것이다.
핵 수용체 프로모터를 표적하는 전달 가능한 인공 전사 인자
핵 수용체 프로모터 내부로 특이적 표적 부위를 표적하는 특이적 육량체 아연 집게 단백질은 ZiFit software v3.3 (Sander J.D., Nucleic Acids Research 35, 599-605)을 이용하여 Barbas 아연 집게 모듈 셋(Barbas zinc finger module set)(Gonzalez B., 2010, Nat Protoc 5, 791-810)으로 구성되거나, 향상된 효모 하나 하이브리드 스크리닝을 이용하여 선별된다. 활성화를 생산하기 위하여, 카텝신 B-민감성, 글루코코르티코이드 수용체를 표적하는 전달 가능한 인공 전사 인자, 육량체 아연 집게 단백질 GR_ZFP1 (서열번호 191), GR_ZFP2 (서열번호 192), 및 GR_ZFP_3 (서열번호 193)는 단백질 전달 도메인 TAT 뿐만 아니라 인공 전사 인자 GR1akt (서열번호 194), GR2akt (서열번호 195) 및 GR3akt (서열번호 196) 수득된 전사 활성 도메인 VP64에 융합되어 있다. 음성 조절 활성을 가지는 전달 가능한 카텝신 B 민감성 인공 전사 인자를 생산하기 위해, 육량체 아연 집게 단백질은 단백질 전달 도메인 TAT 뿐만 아니라 인공 전사 인자 GR1rep (서열번호 197), GR2rep (서열번호 198) 및 GR3rep (서열번호 199)으로 수득된 전사 억제 도메인 SID로 융합된다.
AR-특이적 육량체 아연 집게 단백질은 AR_ZFP1 (서열번호 200), AR_ZFP2 (서열번호 201), AR_ZFP3 (서열번호 202), AR-236A (서열번호 203), AR-236B (서열번호 204), 및 AR-236C (서열번호 205)이다. 인공 전사 인자를 포함하는 AR-특이적 카텝신 B 민감성 VP64- (akt) 또는 SID- (repS)의 결과는 AR1akt (서열번호 206), AR1repS (서열번호 207), AR2akt (서열번호 208), AR2repS (서열번호 209), AR3akt (서열번호 210), AR3repS (서열번호 211), AR-236Aakt (서열번호 212), AR-236ArepS (서열번호 213), AR-236Bakt (서열번호 214), AR-236BrepS (서열번호 215), AR-236Cakt (서열번호 216), 및 AR-236CrepS (서열번호 217)이다.
활성화를 생산하기 위하여, 카텝신 B-민감성, 에스트로겐 수용체를 표적하는 전달 가능한 인공 전사 인자, 육량체 아연 집게 단백질 ER_ZFP1 (서열번호 218), ER_ZFP2 (서열번호 219), 및 ER_ZFP_3 (서열번호 220)는 단백질 전달 도메인 TAT 뿐만 아니라 인공 전사 인자 ER1akt (서열번호 221), ER2akt (서열번호 222) 및 ER3akt (서열번호 223) 수득된 전사 활성 도메인 VP64에 융합되어 있다. 음성 조절 활성을 가지는 전달 가능한 카텝신 B 민감성 인공 전사 인자를 생산하기 위해, 육량체 아연 집게 단백질은 단백질 전달 도메인 TAT 뿐만 아니라 인공 전사 인자 ER1rep (서열번호 224), ER2rep (서열번호 225) 및 ER3rep (서열번호 226)으로 수득된 전사 억제 도메인 SID로 융합된다.
또한, 본 발명의 오량체(pentameric), 육량체(hexameric), 7량체(heptameric) 또는 8량체(octameric) 아연 집게 단백질을 포함하는 인공 전사 인자를 고려하며, 여기서 각각의 아연 집게 모듈은 각각의 핵 수용체 프로모터 유전자의 표적 부위에 대하여 결합 친화도를 향상시키기 위해 또는 내성을 증가시기기 위한 아연 집게 단백질의 면역원성 프로파일을 변경하기 위해 교환된다.
다른 실시형태에서, 본 발명에 따른 특정 핵 수용체 유전자 프로모터를 표적으로 하는 인공 전사 인자는 서열번호 191 내지 193, 200 내지 205, 218 내지 220의 아연 집게 모듈 조성물에 기초한 아연 집게 단백질을 포함하며, 여기서 최대 셋, 바람직하게는 하나 또는 두 개의 개별 아연 집게 모듈이 표적 서열에 인공 전사 인자 결합을 조절하는 대안적인 결합 특성을 가지는 다른 아연 집게 모듈에 교환되고, 및/또는 여기서 최대 12, 예를 들어 12, 11 10 또는 9, 바람직하게는 9, 7, 6 또는 5, 바람직하게는 4, 3, 더욱 바람직하게는 하나 또는 두 개별적인 아미노산이 의도한 표적 부위에 결합 친화도를 유지하는 동안 잠재적인 면역원성을 최소화하기 위해 교환된다.
구체적인 실시형태에서, 핵 수용체 유전자 프로모터를 표적화하는 인공 전사 인자는 서열번호 191 내지 193, 200 내지 205, 218 내지 220의 아연 집게 모듈 조성물에 기초한 아연 집게 단백질을 포함하며, 여기서 선택적으로 최대 셋, 바람직하게는 하나 또는 둘, 개별적 아연 집게 모듈인 표적 서열에 인공 전사 인자의 결합을 조절하는 대안적인 결합 특성을 가지는 다른 아연 집게 모듈로 변환하며, 및/또는 여기서 선택적으로 최대 12, 가장 바람직하게는 하나 또는 두 개의 개별적 아미노산이 의도된 표적 부위에 결합 친화도를 유지하는 동안 잠재적 면역원성을 최소화하기 위해 변환되며, 및 여기서 전사 조절 도메인은 VP16, VP64, CJ7, p65-TA1, SAD, NF-1, AP-2, SP1-A, SP1-B, Oct-1, Oct-2, Oct2-5x, MTF-1, BTEB-2, LKLF, N-KRAB, C-KRAB, SID 또는 ERD이다. 보다 구체적으로, 본 발명은 엔조솜 특이적 부위가 카텝신 B 절단 부위인 인공 전사 인자, 및 엔도솜 특이적 부위가 잠재적 면역원성 또는 절단 특이성 또는 효율성을 최소화하기 위해 변경된 카텝신 B 절단 부위인 인공 전사 인자인 인공 전사 인자에 관한 것이다.
단상부족성 ( haploinsufficient ) 유전자 프로모터를 표적화하는 전달 가능한 인공 전사 인자
특이적 육량체 아연 집게 단백질은 ZiFit software v3.3 (Sander J.D., Nucleic Acids Research 35, 599-605)을 이용하여 Barbas 아연 집게 모듈 셋(Barbas zinc finger module set)(Gonzalez B., 2010, Nat Protoc 5, 791-810)으로 구성되거나 향상된 효모 하나 하이브리드 스크리닝을 이용하여 선별된다.
OPA1-특이적 육량체 아연 집게 단백질은 OPA1_ZFP1 (서열번호 227), OPA1_ZFP2 (서열번호 228), OPA1-916B (서열번호 229), OPA1-916C (서열번호 230), OPA1-916D (서열번호 231), OPA1-916E (서열번호 232), OPA1-18B (서열번호 233), OPA1-18C (서열번호 234), OPA1-18D (서열번호 235), OPA1-18E (서열번호 236), OPA1-165A (서열번호 237), OPA1-165B (서열번호 238), OPA1-165C (서열번호 239), OPA1-165D (서열번호 240), OPA1-165E (서열번호 241), OPA1-165F (서열번호 242), OPA1-165G (서열번호 243), 및 OPA1-165H (서열번호 244)이다. 전사 인자를 함유하는 OPA1-특이적 카텝신 B 민감성 인공 VP64에 대응하는 것은 OPA_akt1 (서열번호 245), OPA_akt2 (서열번호 246), OPA1-916Bakt (서열번호 247), OPA1-916Cakt (서열번호 248), OPA1-916Dakt (서열번호 249), OPA1-916Eakt (서열번호 250), OPA1-18Bakt (서열번호 251), OPA1-18Cakt (서열번호 252), OPA1-18Dakt (서열번호 253), OPA1-18Eakt (서열번호 254), OPA1-165Aakt (서열번호 255), OPA1-165Bakt (서열번호 256), OPA1-165Cakt (서열번호 257), OPA1-165Dakt (서열번호 258), OPA1-165Eakt (서열번호 259), OPA1-165Fakt (서열번호 260), OPA1-165Gakt (서열번호 261), 및 OPA1-165Hakt (서열번호 262)이다.
또한, 본 발명의 오량체(pentameric), 육량체(hexameric), 7량체(heptameric) 또는 8량체(octameric) 아연 집게 단백질을 포함하는 인공 전사 인자를 고려하며, 여기서 각각의 아연 집게 모듈은 각각의 단상부족성 프로모터 유전자의 표적 부위에 대하여 결합 친화도를 향상시키기 위해 또는 내성을 증가시기기 위한 아연 집게 단백질의 면역원성 프로파일을 변경하기 위해 교환된다.
다른 실시형태에서, 본 발명에 따른 특정 단상부족성 유전자 프로모터를 표적으로 하는 인공 전사 인자는 서열번호 227 및 244의 아연 집게 모듈 조성물에 기초한 아연 집게 단백질을 포함하며, 여기서 최대 셋, 바람직하게는 하나 또는 두 개의 개별 아연 집게 모듈이 표적 서열에 인공 전사 인자 결합을 조절하는 대안적인 결합 특성을 가지는 다른 아연 집게 모듈에 교환되고, 및/또는 여기서 최대 12, 더욱 바람직하게는 하나 또는 두 개별적인 아미노산이 의도한 표적 부위에 결합 친화도를 유지하는 동안 잠재적인 면역원성을 최소화하기 위해 교환된다.
구체적인 실시형태에서, 단상부족성 유전자 프로모터를 표적화하는 인공 전사 인자는 서열번호 227 및 244의 아연 집게 모듈 조성물에 기초한 아연 집게 단백질을 포함하며, 여기서 선택적으로 최대 셋, 바람직하게는 하나 또는 둘, 개별적 아연 집게 모듈인 표적 서열에 인공 전사 인자의 결합을 조절하는 대안적인 결합 특성을 가지는 다른 아연 집게 모듈로 변환하며, 및/또는 여기서 선택적으로 최대 12, 가장 바람직하게는 하나 또는 두 개의 개별적 아미노산이 의도된 표적 부위에 결합 친화도를 유지하는 동안 잠재적 면역원성을 최소화하기 위해 변환되며, 및 여기서 전사 조절 도메인은 VP16, VP64, CJ7, p65-TA1, SAD, NF-1, AP-2, SP1-A, SP1-B, Oct-1, Oct-2, Oct2-5x, MTF-1, BTEB-2, LKLF, N-KRAB, C-KRAB, SID 또는 ERD이다. 보다 구체적으로, 본 발명은 엔조솜 특이적 부위가 카텝신 B 절단 부위인 인공 전사 인자, 및 엔도솜 특이적 부위가 잠재적 면역원성 또는 절단 특이성 또는 효율성을 최소화하기 위해 변경된 카텝신 B 절단 부위인 인공 전사 인자인 인공 전사 인자에 관한 것이다.
수용체 프로모터 활성 조절에서 인공 전사 인자의 활성
수용체 프로모터에 의해 구동된 전사에 영향을 주는 인공 전사 인자의 잠재성을 평가하기 위해, 루시퍼라제 수용체 분석이 수행되었다(도 2). 이를 위해, ETRA 프로모터로부터 발현의 구동이 가능한 HeLa 세포는 이중 수용체 플라스미드와 함께 인공 전사 인자 발현 플라스미드와 공동 배양되었다. 상기 이중 수용체 플라스미드는 NEG-PG04 및 EF1a-PG04 플라스미드(GeneCopoeia, Rockville, MD)에 기초한 구조적인 CMV 프로모터의 대조군 하에서 분비된 알칼리성 포스파타제(SEAP) 를 위한 유전자와 함께 ETRA 프로모터의 대조군 하에서 분비된 Gaussia 루시퍼라제 유전자를 포함한다. 상기 공동 형질감염은 상기 수용체 플라스미드 및 Gaussia 루시퍼라제로 형질감염된 세포에서 인공 전사 인자 발현의 존재를 확인하기 위해 3:1의 인공 전사 인자 발현 플라스미드:수용체 플라스미드의 비율에서 수행되며, SEAP 활성은 제조업자의 권고사항(Gaussia Luciferase Glow Assay Kit, Pierce; SEAP Reporter Gene Assay Chemiluminescence, Roche)에 따라 측정된다. 루시퍼라제 값은 SEAP 활성으로 표준화되고 100%로 설정된 황색 형광 단백질(YFP)로 표시되는 대조군 세포와 비교한다. 형질감염된 세포의 상등액에서 루시퍼라제 및 SEAP 활성 간의 비율 측정에 의해, 오직 인공 전사 인자 플라스미드로 형질감염된 세포 내에서 SEAP 발현에 대한 루시퍼라제 발현을 구동시킨 수용체 프로모터의 표준화가 가능했다. 이러한 접근은 상이한 실험 간의 형질 감염 효율에 있어서 상이함을 확인하고 표준화하는데 유용함을 증명하며, 주어진 수용체 프로모터의 조절을 매개하는 인공 전사 인자의 정량을 위해 허용된다. 루시퍼라제 발현 연구는 적어도 세번, 형질감염된 대조군 세포와 비교하여 세 번의 반복 실험, 평균, 대조군의 %에서 상대적인 루시퍼라제 활성(RluA)로 나타내며 SEM으로 묘사된 오차 막대로 표시한다. AO74V의 발현은 대조군 세포에 비해 ETRA 프로모터 구동 발현을 3.2%로 억제하였다.
내생 유전자에서 ETRA -특이적 인공 전사 인자 AO74V 를 위한 ETRA _ TS +74 결합 부위의 접근성
조절 활성을 발휘하기 위해, 인공 전사 인자는 내생 유전체 영역의 맥락에서 이들의 표적 부의에 결합할 수 있어야 한다. ETRA+74V zinc finger protein (서열번호 80)를 포함하는 인공 전사 인자가 ETRA 유전자(ETRA_TS+74, 서열번호 41)에서 이들의 표적 부위에 결합할 수 있는지를 확인하기 위해, 테트라사이클린 유도성 프로모터의 대조군 하에서 AO74V를 위한 발현 구조체를 포함하는 안정한 세포주를 생성하였다. 24시간 동안 테트라사이클린으로 유도한 상기 세포들은 AO74V 단백질(서열번호 263) 생산을 야기하였으며, 반면에 테트라사이클린 부재에서는 AO74V가 생산되지 않았다. 도 3A에 나타낸 바와 같이, AO74V의 발현은 유도되지 않은 세포 또는 DAN 결합 능력 또는 공 벡터 대조군이 결여된 비활성화 변이 AO74V를 발현하는 세포와 비교하여 HEK 293 FlpIn 세포에서 ETRA mRNA의 거의 완벽한 손실을 야기한다. 도 3A에서 세포가 FlpIn 부위로 통합된 발현 구조체를 포함하는 반면에, 도 3B에서 나타낸 HEK 293 FlpIn TRex 세포는 AAVS1 safe harbor locus에서 테트라사이클린 유도성 발현 구조체를 포함한다. 또한 상기 세포에서, 비활성 AO74V이 아닌 AO74V의 발현은 ETRA 발현의 거의 완벽한 억제를 야기한다. AAVS1 locus에서 AO74V, 비활성 AO74V 또는 공 벡터 대조군을 위한 테트라사이클린 유도성 발현 구조체를 안정적으로 포함하는 HeLa 세포를 다시 이용하여, 테트라사이클린을 이용한 비활성 AO74V가 아닌 AO74V의 유도는 ETRA 발현의 강한 억제 결과를 나타냈다. 종합적으로, 내재적 ETRA 프로모터에서 ETRA_TS+74 표적 부위는 인공 전사 인자에 접근가능하고, 상기 표적 부위에의 결합에 따른 SID 음성 조절 도메인을 포함하는 인공 전사 인자는 ETRA 발현 억제를 위한 허용 가능한 위치이다.
ETRA -특이적 인공 전사 인자의 발현 후 칼슘 신호에 의존적인 ET -1의 평가
ETRA 작용제 ET-1는 HEK 293 FlpIn TRex 세포에서 칼슘 플럭스를 자극한다. 따라서, ETRA 발현의 억제는 ET-1 세포로 자극된 후 세포 내 칼슘 농도의 변화 억제가 기대된다. AO74V (서열번호 263)를 발현하는 HEK 293 FlpIn TRex는 48시간 동안 테트라사이클린으로 유도되며 0, 100, 1000 nM 의 ET-1로 처리되고 칼슘 플럭스는 자동화된 형광 플레이트 리더기(FlexStation 3, Molecular Devices)를 이용한 칼슘 민감성 형광 염료(Calcium 5 Assay Kit, Molecular Devices)를 이용하여 측정하였다. 테트라사이클린으로 유도되지 않은 세포는 대조군으로 사용하였다. 도 4A에 나타낸 바와 같이, ET-1은 인공 전사 인자를 발현하지 않는 세포에서 세포 내의 칼슘 농도의 농도 의존적 증가를 유도할 수 있는 반면에, ETRA 특이적 인공 전사 인자를 발현하는 세포는 더이상 ET-1 자극에 반응하지 않는다(도 4B). 이러한 데이타는 상기 인공 전사 인자의 발현 후 ETRA 단백질의 결여로 인해 ETRA 의존적 신호의 손실과 일치한다.
ETRA -특이적 인공 전사 인자의 적용 후 인간 자궁 평활근 세포의 ET -1 의존성 수축의 평가
평활근 세포(SMCs)는 ETRA를 발현하고 ET-1 노출 후 수축할 수 있다. 항-ETRA 프로모터 인공 전사 인자 ETRA+74VrepSNPS (서열번호 142)의 효율을 측정하기 위해, 인간 자궁 평활근 세포(hUtSMCs)를 모델 시스템으로 사용하였다. 이를 위해, hUtSMCs는 3차원 콜라겐 격자에 삽입하고, 1 μM ETRA+74VrepSNPS 또는 버퍼 대조군을 0 또는 100 nM의 ET-1에 노출 전 3일간 처리하였다. 단백질 또는 버퍼 처리는 매 24시간 반복하였다. 지지대로부터 격자의 분리 후 ET-1을 추가하여 격자의 수축을 관찰하였다. 도 5에 나타낸 바와 같이, ET-`에 노출된 대조군 격자는 ET-1으로 처리되지 않은 격자와 비교하여 약 78%까지 수축하였다. 대조적으로, ETRA+74VrepSNPS 처리된 격자는 ET-1으로 처리되지 않은 대조군 격자와 비교하였을 때 ET-1의 존재에서 유의적으로 수축하지 않았다. 이는 ETRA+74VrepNPS으로 처리된 후 hUtSMCs의 수축이 유도된 ET-1의 완벽한 차단과 일치한다. 도 4에 나타낸 바와 같이 6개 한벌(sextuplicates)에서 행해진 세 번의 독립적인 실험의 ET-1 추가 후 9시간에 평균 격자 영역을 나타낸다. 일반 선형 변량 모델을 사용하는 SPSS 소프트웨어 패키지를 사용한 통계 분석은 ETRA+74VrepNPS의 차단 활성에 높은 유의성(**는 p<0.001)을 나타내었다.
카텝신 B-민감성 ETRA 특이적 인공 전사 인자의 증가된 핵 국소화
엔도솜 특이적 프로테아제 절단 사이트의 첨가가 실제로 본 발명의 인공 전사 인자의 세포 내 표적을 향상시키는지를 확인하기 위해, HeLa 세포는 ETRA 특이적 인공 전사 인자 단백질 ETRA+74VrepSNPS(SID 음성 조절 도메인을 포함하는 카텝신 B 부위가 결여된 ETRA+74VrepS 변이체) 또는 카텝신 B 민감적 ETRA+74VrepS 단백질로 형질도입되었으며, 핵 국소화는 이미지 분석에 의해 형광 현미경으로 분석되었다. 도 6에 나타낸 바와 같이, 카텝신 B 절단 사이트의 혼입은 핵에서 인공 전사 인자의 평균 농도를 4.7배 증가시켰다. 카텝신 B 민감적 ETRA+74VrepS로 형질 도입된 세포는 또한 최대 농도 47.5%에 이르는 세포의 75%가 핵 내로 인공 전사 인자의 더욱 균일한 흡수를 나타내었으며, 반면에 카텝신 B 둔감성 ETRA+74VrepSNPS로 형질 도입된 세포의 75%는 최대 농도의 10.4% 이하이다. 이러한 데이터는 인공 전사 인자의 나머지로부터 TAT 단백질 전달 도메인의 분리 결과를 나타내는 엔도솜 구획에서 ETRA+74VrepS의 카텝신 B 의존적 절단과 일치한다. 이는 일단 확률적인 소포체의 파열이 일어난 ETRA+74VrepS의 인공 전사 인자 부분의 엔도솜 구획으로부터 효율적으로 배출될 수 있다.
카텝신 B 부위의 봉입체는 루시퍼라제 리포터 분석에서 전달 가능한 인공 전사 인자의 활성을 증가시킨다
위와 같이, 상기 카텝신 B 민감적 ETRA 특이적 인공 전사 인자 ETRA+74VrepS는 카텝신 B 둔감성 ETRA+74VrepSNPS과 비교하여 단백질 전달 후 액 구획에 보다 효율적으로 국소화된다. 이러한 개선된 핵 국소화가 전사 조절의 측면에서 증가된 활성으로 변환하는지를 평가하기 위해, 루시퍼라제 리포터 분석을 수행하였다. 이를 위해, 하이브리드 CMV/ETRA_TS+74 및 분비된 알칼리 포스파타제의 대조군 하에서 Gaussia 루시퍼라제로 구성된 리포터 구조체를 함유하는 HEK 293 세포는 2시간 동안 1 μM ETRA+74VrepS, ETRA+74VrepSNPS 또는 대조군으로써 비활성 버전 ETRA+74VrepS를 처리하였으며, 루시퍼라제 및 분비된 알칼리 포스파타제 활성은 처리 후 24시간에 측정되었다. 도 7에 나타낸 바와 같이, 루시퍼라제 활성은 대조군과 비교하여 ETRA+74VrepSNPS로 처리 후 57.9 +/- 5.8% 감소하였으며, 반면에 ETRA+74VrepS 처리는 루시퍼라제 활성을 87.2 +/- 8.2%로 감소시켰다. 이러한 데이터는 전사 조절의 관점에서 증가된 카텝신 B 매개의 엔도솜 배출이 증가된 활성으로 변환하기 때문에 인공 전사 인자의 핵 국소화를 증가시킨다는 개념을 지원한다.
각 인공 전사 인자에 응답하는 하이브리드 CMV 프로모터 하에서 루시퍼라제를 함유하는 리포터 세포주를 이용한 TLR4, AR, 또는 FcER1A 프로모터를 표적으로 하는 카텝신 B 민감적 인공 전사 인자와 각각의 카텝신 B 둔감적 변이체를 비교할 때 유사한 결과를 얻었다. 도 8에 나타낸 바와 같이, 카텝신 B 민감적 TLR4 222BrepS 인공 전사 인자로 적절한 리포터 세포의 처리는 대조군 처리된 세포와 비교하여 61.3 +/- 6.9%의 상대적인 루시퍼라제 활성을 감소시킨 반면에, 카텝신 B 둔감적 TLR4 222BrepSNSP의 처리는 루시퍼라제 활성을 억제하지 않았다. 비슷하게, 카텝신 B 절단 AR 236ArepS로 적절한 리포터 세포의 처리는 대조군과 비교하여 상대적인 루시퍼라제 활성을 52 +/- 11%로 감소시킨 반면에, AR 236ArepSNPS의 처리는 처리된 대조군 세포의 오직 85 +/- 11%의 루시퍼라제 활성을 감소시켰다. 또한, 카텝신 B 민감적 IgER 147ArepS으로 적절한 리포터 세포의 처리는 처리된 대조군 세포와 비교하여 상대적인 루시퍼라제 활성을 52.7 +/- 12.9% 감소를 야기하였으며 반면에, 카텝신 B 민감적 IgER 147ArepSNPS는 대조군 세포와 비교하여 루시퍼라제 활성 감소를 나타내지 않았다. 종합적으로, 전달 가능한 인공 전사 인자로의 카텝신 B 절단 부위의 봉입체는 이들의 올바른 핵 국소화 뿐만 아니라 전사 조절의 관점에서 이들의 활성을 크게 향상시킨다. 따라서, 엔도솜 프로테아제의 작용을 통해 인공 전사 인자로부터 세포 막의 높은 친화도를 가지는 단백질 전달 도메인의 분리는 엔도솜 소체의 파열 후 활성 인공 전사 인자의 효율적인 배출을 허용한다.
ETRA 특이적 카텝신 B 민감적 인공 전사 인자는 인간 조직에서 활성을 나타낸다
ETRA 특이적 인공 전사 인자의 작용을 통한 ETRA 발현의 억제는 엔도텔린 의존성, ETRA 매개 세포 신호에 방해할 것으로 예상된다. 엔도텔린은 공지된 가장 강력한 혈관 수축제(vasoconstrictor)이며, 따라서 상기 엔도텔린 수용체 ETRA의 하양 조절은 엔도텔린 의존성 혈관 수축을 차단하는 것으로 예상된다. ETRA+74VrepS가 ETRA 수준에 영향을 미칠 수 있어서 엔도텔린 의존성 혈관 수축을 차단하는지를 평가하기 위해, ETRA+74VrepS로 처리된 생체 외 인간 혈관의 혈관 수축을 측정하였다. 이를 위해, 분리된 인간 관상 동맥 혈관 고리는 3일 동안 1 μM ETRA+74VrepS의 존재 하에서 배양되었다. 대조군으로써 사용된 용매대조군을 같이 배양하였다. 혈관 수축성을 평가하기 위해, 혈관 고리는 wire myograph로 계수되었고, ETRA 독립적 혈관 수축 U46619에 반응하는 혈관뿐만 아니라 엔도텔린의 농도 증가를 측정하였다. 도 11에 나타낸 바와 같이, ETRA+74VrepS로 처리된 것은 용매 처리된 대조군 혈관과 비교하여 상대적인 엔도텔린 의존적 혈관 수축을 감소시켰다. 이러한 데이터는 ETRA+74VrepS의 죽음 작용을 통해, ETRA 단백질 수준의 감소에서 초래한 ETRA 유전자 발현의 하향 조절 및 인간 관상 동맥에서 엔도텔린 의존적인 혈관 수축에서 순차적 감소와 일치한다.
FCER1A -특이적, 카텝신 B 민감적 인공 전사 인자 IgER -147 ArepS 는 과민성 쇼크( anaphylactic shock)의 인간화 마우스 모델에서 활성을 나타낸다
다가 항원의 결합을 통한 비만세포 또는 호염기구(basophiles)에서 IgE 수용체의 가교는 히스타민 및 이러한 세포로부터의 다른 알러지 매개 물질의 방출을 일으키는 원인이 된다. 처리의 시스템 활성화의 경우, 예를 들어, 알레르기 항원에 전신 노출에 따라 히스타민의 전신 방출은 과민성 쇼크에 다른 알레르기 매개체와 함께 발생한다. 과민성 쇼크는 부종, 혈압의 저하 및 저체온증(hypothermia)에 의해 특징지어진다. 동물에서 과민증을 모델링하기 위해, 하기의 전략을 적용하였다: 동물은 예를들어 dinitrophenyl (DNP)에 대하여 발생되는 특이적 IgE 항체의 주입을 통해 감응한다. 주입된 특이적 IgE는 알레르기 매개 물질을 방출하기 위해 프라이밍된 비만세포 및 호염기구에서 IgE 수용체에 결합한다. 이러한 세포를 활성화하기 위해, 높은 몰비에서 BSA에 결합된 DNP는 주입되어 결합 특이적 항-DNP IgE를 통해 IgE 수용체의 가교결합에 이르게 한다.
IgER-147ArepS가 IgE 수용체의 손실을 이끄는 FCER1A-프로모터를 표적으로 하는 것에 따라, 상기 인공 전사 인자 전처리는 알레르기 매개 물질의 방출이 IgE 수용체에 따르는 것처럼 아나필락시스의 유도를 방해한다. 생체 내 모델에서 IgER-147ArepS의 활성의 측정은 이러한 인공 전사 인자는 인간 FCER1A 프로모터에 대하여 선택되며 쥐과의 FCER1A 프로모터로부터 발현을 억제할 것으로 예상되지 않기 때문에 인간화된 마우스 모델(hNSG)이 선택되었다. hNSG 모델은 심각한 면역 저하 nsg 마우스를 기초로 하였으며, 이는 마우스에서 인간 유사 면역 시스템을 생성할 수 있는 인간 CD34+ 줄기세포로 이식되었다. 도 12에 나타낸 바와 같이, anti-DNP IgE/DNP-BSA을 이용하여 아나필락스 유도 전 5일 및 2일에 IgER-147ArepS 인공 전사 인자로 두 번 전처리된 hNSG 마우스는 대조군 동물과 비교하여 과민성 쇼크에 덜 민감하였다. 용매로 처리된 대조군 동물에서 아나필락시스는 유도 후 10분에서 동물의 빠른 죽음을 초래하였던 반면에, IgER-147ArepS 처리된 동물은 6분 동안 아나필락시스에서 살아남았다. 이러한 데이터는 IgER-147ArepS으로 처리된 후 감소된 IgER 활성을 통해 아나필락시스의 억제를 명확하게 알려주는 것이다.
폴리에틸렌 글리콜 잔기의 부착
본 발명의 인공 전사 인자에 폴리에틸렌 글리콜 잔기(PEGylation)의 공유 결합은 인공 전사 인자의 용해도를 증가시키고, 신장 청정(renal clearance)을 감소시키며, 이의 면역원성을 제어하는 것으로 간주된다. 1 내지 40 킬로달톤의 크기의 범위에서 아민(amine) 뿐만 아니라 티올(thiol) 반응성 폴리에틸렌 글리콜로 간주한다. 티올 반응성 폴리에틸렌 글리콜을 사용하여, 인공 전사 인자의 부위 특이적 PEG화(PEGylation)는 달성된다. 본 발명의 인공 전사 인자에서 아미노산을 포함하는 필수적인 유일한 티올 그룹은 필수적인 아연 배위(coordination)를 위한 아연 집게 모듈에 위치한 시스테인 잔기이다. 이러한 티올 그룹은 이들의 아연 배위 때문에 PEG화에 접근할 수 없어서, 본 발명의 인공 전사 인자로의 하나 또는 여러 시스테인 잔기의 봉입체는 티올 특이적 폴리에틸렌 글리콜 제제를 이용한 PEG화를 위한 자유 티올 그룹을 제공한다.
약학적 조성물
본 발명은 또한 상기 정의된 인공 전사 인자를 포함하는 약학적 조성물을 제공한다. 고려되는 약학적 조성물은 전신성 비경구 투여를 위한 조성물, 구체적으로는 정맥내 투여(intravenous administration)이고, 흡입을 위한 조성물, 및 국부적 투여를 위한 조성물, 구체적으로는 안과의 국소적 투여(ophthalmic-topical administration)이고, 예를 들면, 점안약, 눈가용 젤 및 스프레이, 또는 유리체내(intravitreal), 결막하(subconjunctival), parabulbar, 교후부 투여(retrobulbar administration)이고, 온혈 동물, 구체적으로 인간에 대한 것이다. 구체적으로 바람직하게는 점안약 및 눈가용 젤 및 유리체내, 결막하, parabulbar 또는 교후부 투여를 위한 조성물이다. 상기 조성물은 단독으로 활성 성분을 포함하거나, 바람직하게는 약학적으로 허용 가능한 담체를 같이 포함한다. 또한 서방형 제제로써 고려된다. 상기 활성 성분의 투여량은 치료될 대상이 되는 종, 아니, 무게, 및 개별 상태, 개별 약동학 테이다, 및 투여 방식에 따른다.
또한 경구 전달에 유용한 약학적 조성물로 고려되며, 구체적으로 적절히 캡슐화된 활성성분 또는 장 내 분해에 대해 보호되는 다른 성분을 포함하는 조성물이다. 예를 들어, 상기 약학적 조성물은 막 투과성 향상제, 프로테아제 효소 저해제, 및 장용 코팅제에 의해 포장될 수 있는 것을 포함할 수 있다.
약학적 조성물은 약 1% 내지 95% 활성 성분을 포함한다. 단위 투여 형태는 예를 들어, 앰플, 바이알, 흡인제, 점안제, 눈 젤 등이 있다.
본 발명의 약학적 조성물은 그 자체로 공지된 방식인, 예를 들어 통상적인 혼합, 용해 또는 동결 건조 방식에 의해 제조된다.
바람직한 것은 활성 성분의 용액, 및 현탁액 또는 분산액, 특히 등장 수용액, 분산액 또는 현탁액의 사용에 주어지며, 이는 예를 들어 만니톨과 같은 담체와 함께 또는 단독으로 활성 성분을 포함하는 동결 건조된 조성물의 경우에서 사용 전 구성될 수 있다. 약학적 조성물은 멸균될 수 있고 또는 첨가제, 예를 들면 보존제, 안정제, 습윤제 및/또는 유화제, 용해제, 삼투압 및/또는 버퍼를 조절하기 위한 염을 포함할 수 있고 공지된 방식, 예를 들어 용해 및 동결 건조 공정의 방법에 의해 제조된다. 상기 용액 또는 현탁액은 점도 증가제, 전형적 나트륨 카르복시 메틸 셀룰로오스(sodium carboxymethylcellulose), 카르복시 메틸 셀룰로오스(carboxymethylcellulose), 덱스트란(dextran), 폴리비닐 피롤리돈(polyvinylpyrrolidone), 또는 젤라틴(gelatins), 또는 또한 가용화제(solubilizers), 예를 들면 Tween 80TM (polyoxyethylene(20)sorbitan mono-oleate)를 포함할 수 있다
오일 중 현탁액은 식물성, 합성 또는 주사 목적의 통상적인 반합성 오일을 포함한다. 특별히 언급되는 바에 의하면, 8 내지 22, 특히 12 내지 22개의 탄소 원자를 가지는 장쇄 지방산 성분의 산으로써 포함되는 액체 지방산 에스테르로 제조될 수 있다. 이러한 지방 에스테르의 알콜 성분은 최대 6 탄소를 가지며 일가(monovalent) 또는 다가(olyvalent), 예를 들면 모노(mono-), 이가(di-) 또는 3가(trivalent) 알콜, 구체적으로는 글리콜 및 글리세롤이다. 지방산 에스테르 혼합물로써, 면실유(cottonseed oil), 아몬드유(almond oil), 올리브유(olive oil), 피마자유(castor oil), 참기름(sesame oil), 대두유(soybean oil) 및 땅콩기름(groundnut oil)과 같은 식물성 오일은 특히 유용하다.
주사용 제제의 제조는 일반적으로 멸균된 조건 하에서, 예를 들면 앰풀 또는 바이알 속으로의 충전, 및 용기의 밀봉으로 수행된다.
비경구 투여(parenteral administration)를 위한, 수용성 형태, 예를 들어 점도 증가 물질, 예를 들어 소듐 카르복실메틸셀룰로오스(sodium carboxymethylcellulose), 솔비톨(sorbitol) 및/또는 덱스트란(dextran)을 함유하는 수용성 염 또는 수용성 주사 현탁액에서 활성 성분의 수용액, 및 필요하다면 안정화제가 특히 적합하다. 상기 활성 성분은 선택적으로 부형제와 함께 동결건조의 형태가 될 수 있으며, 적절한 용매의 첨가에 의해 비경구 투여 전 용액으로 제조될 수 있다.
흡입을 위한 조성물은 스프레이, 미스트 또는 투하의 형태와 같이 에어로졸 형태로 투여될 수 있다. 에어로졸은 특정 약물의 양을, 예를 들어 디클로로디플루오로 메탄(dichlorodifluoro-methane), 트리클로로 플루오로 메탄(trichlorofluoromethane), 디클로로 테트라 플루오로 에탄(dichlorotetrafluoroethane), 이산화탄소(carbon dioxide) 또는 다른 적합한 가스, 환자에 의해 흡입되는 에어로졸 의약품의 짧은 버스트 형태의 적합한 추진제를 사용하여 기도 또는 폐로 전달하는 계량된 용량 흡입기 또는 분무기로 전달될 수 있는 용액 또는 현탁액으로부터 제조된다. 이는 또한 락토스 또는 전분과 같은 적절한 분말 염기로 흡입을 위한 분말 스프레이를 제공할 수 있다.
점안액은 바람직하게는 눈물샘 유체(lacrimal fluid)(295-305 mOsm/l)를 가지는 등장 조성물을 제공하는 적합한 제제를 포함하는 활성 성분의 등장성 수용액이다. 고려되는 제제는 염화나트륨, 시트르산, 글리세린, 소르비톨, 만니톨, 에틸렌 글리콜, 프로필렌 글리콜, 덱스트로스 등이 있다. 또한, 조성물은 예를 들어 pH 5 및 8 사이, 바람직하게는 7.0 내지 7.4를 유지하기 위해, 인산 완충액, 시트르산-인산 완충액, 또는 트리스 완충액(tris(hydroxymethyl)-aminomethane)과 같은 완충제를 포함한다. 상기 조성물은 또한 항균성 방부제(antimicrobial preservatives), 예를 들어 파라벤(parabens), 벤잘코늄 클로라이드(benzalkonium chloride), 폴리헥사메틸렌 비구아니드(polyhexamethylene biguanidine (PHMB)) 등과 같은 사차 암모늄염(quaternary ammonium salts)을 포함할 수 있다. 점안액은 또한 젤 상의 점안제를 생산하기 위한 잔탄 검, 및/또는 히알루론산(hyaluronic acid), 메틸셀룰로오스(methylcellulose), 폴리비닐알콜(polyvinylalcohol), 또는 폴리비닐피롤리돈(polyvinylpyrrolidone)과 같은 점도 증진제를 함유할 수 있다.
치료 방법에서 인공 전사 인자의 용도
본 발명은 엔도텔린 수용체 수준을 낮추거나 증가시기기 위해, 엔도텔린에 대한 세포 반응에의 영향에 사용하기 위해, 그리고 특히 눈 질병과 같은 치료에서 사용하기 위해, 엔도텔린에 의해 조절되는 질환의 치료에서 사용하기 위한 상기 기재된 엔도텔린 수용체 A 프로모터에 관한 인공 전사 인자에 관한 것이다. 마찬가지로 본 발명은 이를 필요로 하는 환자에게 엔도텔린 수용체 A 프로모터에 관한 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 엔도텔린에 의해 조절되는 질병 치료 방법에 관한 것이다.
엔도텔린에 의해 조절되는 질병은 예를 들면, 본태성 고혈압(essential hypertension), 폐고혈압증(pulmonary hypertension), 만성심부전증(chronic heart failure)과 같은 심장 혈관계 질병(cardiovascular diseases) 뿐만 아니라 만성 신부전(chronic renal failure)이다. 또한, 신장 보호 전, 도중 및 후에 방사선오페크(radioopaque) 물질의 적용은 엔도텔린의 반응을 무디게 함으로써 얻어진다. 또한, 다발성 경화증은 엔도텔린 시스템에 의해 부정적으로 영향을 받는다.
또한 엔도텔린에 의해 조절되는 질병은 녹내장 성 신경 퇴행(glaucomatous neurodegeneration), 안구 혈액 순환 혈관 조절 장애(vascular dysregulation), 망막 정맥 폐쇄(retinal vein occlusion), 망막 동맥 폐쇄(retinal artery occlusion), 황반부종(macular edema), 연령 관련 황반 변성(age related macula degeneration), 시신경 병증(optic neuropathy), 중심 장액 맥락 망막 병증(central serous chorioretinopathy), 색소성 망막염(retinitis pigmentosa), Susac 증후군, 및 Leber의 유전 시신경 병증(Leber's hereditary optic neuropathy)과 같은 당뇨성 신장 질병(diabetic kidney disease) 또는 안구 질병(eye diseases)이다.
마찬가지로 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양을 투여하는 것을 포함하는 엔도텔린에 의해 조절되는 질병 치료 방법에 관한 것이다. 구체적으로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양을 투여하는 것을 포함하는 신경퇴행성 녹내장, 안구 혈액 순환 혈관 조절 장애 치료 방법에 관한 것이며, 구체적으로는 망막 정맥 폐쇄, 망막 동맥 폐쇄, 황반부 종, 시신경 병증, 중심 장액 맥락 망막 병증, 색소성 망막염, 및 Leber의 유전 시신경 병증 치료 방법에 관한 것이다. 본 발명의 인공 전사 인자의 유효한 양은 치료될 질병의 유형에 따라 그리고 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이타 및 투여 방식에 따른다. 눈에 투여되는 경우, 0.5 내지 1 mg를 매달 유리체 주입하는 것이 바람직하다. 전신 wr용의 경우, 10 mg/kg를 매달 주사하는 것이 바람직하다. 또한, 유리체 내로 서방적 이식이 더욱 바람직하다.
또한 본 발명은 엔도텔린 수용체 B 수준을 낮추거나 증가시기기 위해 엔도텔린에 대한 세포 반응 영향에 사용하기 위해, 그리고 안구 질병과 같이 엔도텔린에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 엔도텔린 수용체 B 프로모터와 관련된 인공 전사 인자에 관한 것이다. 마찬가지로 본 발명은 이를 필요로 하는 환자에게 엔도텔린 수용체 B 프로모터에 관한 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 엔도텔린에 의해 조절되는 질병 치료 방법에 관한 것이다.
ET-1 의존적인 ETRB-매개의 인공 전사 인자에 의해 조절되는 질병은 특정 암, 신경 퇴행성 및 염증 관련 질환이다.
또한 본 발명은 TLR4 수준을 낮추거나 증가시기기 위해 LPS에 대한 세포 반응 영향에 사용하기 위해, 그리고 안구 질병과 같이 LPS에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 TLR4 프로모터와 관련된 인공 전사 인자에 관한 것이다. 마찬가지로 본 발명은 이를 필요로 하는 환자에게 TLR4 프로모터에 관한 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 LPS에 의해 조절되는 질병 치료 방법에 관한 것이다. LPS에 의해 조절되는 질병은 류마티스 관절염, 동맥 경화증, 건선, 크론병, 포도막염, 콘택트 렌즈 관련 각막염, 각막 염증, 화학 요법에 대한 암의 저항성 등이다.
또한 본 발명은 FCER1 수준을 낮추거나 증가시기기 위해 IgE 또는 IgE-항원 복합체에 대한 세포 반응 영향에 사용하기 위해, 그리고 안구 질병과 같이 IgE 또는 IgE-항원 복합체에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 FCER1A 프로모터와 관련된 인공 전사 인자에 관한 것이다.
마찬가지로 본 발명은 이를 필요로 하는 환자에게 FCER1A 프로모터에 관한 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 IgE 또는 IgE-항원 복합체에 의해 조절되는 질병 치료 방법에 관한 것이다. IgE 또는 IgE-항원 복합체에 의해 조절되는 질병은 Coombs 및 Gell 분류(Gell P. and Coombs R. (eds), 1968, Clinical Aspects of Immunology, Blackwell Scientific, Oxford)에 따른 일반 Ⅰ형 반응에 있다. 이러한 반응은 알레르기성 비염, 천식, 아토피성 피부염, 꽃가루 알레르기, 식품 알레르기, 꽃가루 알레르기, 호흡기 알레르기, 애완 동물 알레르기, 먼지 알레르기, 먼지 진드기 알레르기, 알레르기 uriticaria, 알레르기성 폐포염, 알레르기성 아스페르길루스증, 알레르기성 기관지염, 알레르기성 안검염, 알레르기성 접촉 피부염, 알레르기성 결막염, 알레르기성 진균성 부비동염, 알레르기성 위장염, 알레르기성 간질성 신염, 알레르기성 각막염, 알레르기성 후두염, 알레르기성 자반증, 알레르기성 요도염, 알레르기성 혈관염, 습진, 아나필락시스 등을 들 수 있다.
또한, 본 발명은 핵 수용체의 수준을 낮추거나 증가시기기 위해 핵 수용체 리간드에 대한 세포 반응 영향에 사용하기 위해, 그리고 안구 질병과 같이 핵 수용체에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 핵 수용체의 프로모터 영역을 표적으로 조합된 인공 전사 인자에 관한 것이다. 마찬가지로 본 발명은 이를 필요로 하는 환자에게 핵 수용체 프로모터에 관한 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 핵 수용체 리간드에 의해 조절되는 질병 치료 방법에 관한 것이다.
핵 수용체의 리간드에 의해 조절되는 질병은, 예를 들어 부신 기능 부전(adrenal insufficiency), 부신피질 기능 부전(adrenocortical insufficiency), 알콜 중독, 알츠하이머 병, 안드로젠 불감 증후군(androgen insensitivity syndrome), 신경성 식욕 부진, 대 동맥류, 대동맥 판막 경화증, 관절염, 천식, 죽상 경화증(atherosclerosis), 주의력 결핍 과잉 행동 장애, 자폐증, 무정자증(azoospermia), 담도 차 경화증(biliary primary cirrhosis), 양극성 장애, 방광암, 뼈암, 유방암, 심혈관 질환, 심혈관 심근 경색, 복강 질환, 담즙(cholestasis), 만성 신부전 및 대사 증후군, 간경변, 구개열, 대장암, 선천성 부신 기능 부전, 관상 동맥 심장 질환, 잠복, 심부정맥 혈전증, 치매, 우울증, 당뇨 망막 병증, 자궁 내막증, 자궁 내막암, 향상된 S-콘 증후군, 본태성 고혈압(essential hypertension), 가족 일부 지방 이영양증(familial partial lipodystrophy), 아교 모세포종, 글루코 코르티코이드 저항, 그레이브스병, 높은 혈청 지질 농도, hyperapobetalipoproteinemia, 고지혈증(hyperlipidemia), 고혈압, 고 중성 지방 혈증(hypertriglyceridemia), hypogonadotropic hypogonadism, hypospadias, 불임, 염증성 장 질환, 인슐린 내성, 허혈성 심장 질환, 간 지방증, 폐암, 홍 반성 낭창(lupus erythematosus), 주요 우울 장애, 남성 유방암, 대사 혈장 지질 수준, 대사성 증후군, 편두통, 다발성 경화증(mulitple sclerosis), 심근 경색, 신 증후군, non-Hodgkin's lymphoma, 비만, 골관절염, 골감소증, 골다공증, 난소암, 파킨슨병, 자간전증, 프로게스테론성 전립선암, pseudohypoaldosteronism, 건선, 정신 분열증, 정신 이상, 색소성 망막염-37, 정신 분열증, 경화성 담관염, 성별 반전(sex reversal), 피부암, 케네디의 척추 및 안구 위축(spinal and bulbar atrophy of Kennedy), 심근 경색에 대한 감수성, 건선에 대한 감수성, 고환암, I 형 당뇨병, II 형 당뇨병, 자궁암 및 현기증이다.
마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 핵 수용체의 리간에 의해 조절되는 질병을 치료하는 방법에 관한 것이다. 구체적으로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는, 부신 기능 부전(adrenal insufficiency), 부신피질 기능 부전(adrenocortical insufficiency), 알콜 중독, 알츠하이머 병, 안드로젠 불감 증후군(androgen insensitivity syndrome), 신경성 식욕 부진, 대 동맥류, 대동맥 판막 경화증, 관절염, 천식, 죽상 경화증(atherosclerosis), 주의력 결핍 과잉 행동 장애, 자폐증, 무정자증(azoospermia), 담도 차 경화증(biliary primary cirrhosis), 양극성 장애, 방광암, 뼈암, 유방암, 심혈관 질환, 심혈관 심근 경색, 복강 질환, 담즙(cholestasis), 만성 신부전 및 대사 증후군, 간경변, 구개열, 대장암, 선천성 부신 기능 부전, 관상 동맥 심장 질환, 잠복, 심부정맥 혈전증, 치매, 우울증, 당뇨 망막 병증, 자궁 내막증, 자궁 내막암, 향상된 S-콘 증후군, 본태성 고혈압(essential hypertension), 가족 일부 지방 이영양증(familial partial lipodystrophy), 아교 모세포종, 글루코 코르티코이드 저항, 그레이브스병, 높은 혈청 지질 농도, hyperapobetalipoproteinemia, 고지혈증(hyperlipidemia), 고혈압, 고 중성 지방 혈증(hypertriglyceridemia), hypogonadotropic hypogonadism, hypospadias, 불임, 염증성 장 질환, 인슐린 내성, 허혈성 심장 질환, 간 지방증, 폐암, 홍 반성 낭창(lupus erythematosus), 주요 우울 장애, 남성 유방암, 대사 혈장 지질 수준, 대사성 증후군, 편두통, 다발성 경화증(mulitple sclerosis), 심근 경색, 신 증후군, non-Hodgkin's lymphoma, 비만, 골관절염, 골감소증, 골다공증, 난소암, 파킨슨병, 자간전증, 프로게스테론성 전립선암, pseudohypoaldosteronism, 건선, 정신 분열증, 정신 이상, 색소성 망막염-37, 정신 분열증, 경화성 담관염, 성별 반전(sex reversal), 피부암, 케네디의 척추 및 안구 위축(spinal and bulbar atrophy of Kennedy), 심근 경색에 대한 감수성, 건선에 대한 감수성, 고환암, I 형 당뇨병, II 형 당뇨병, 자궁암 및 현기증 치료 방법에 관한 것이다. 본 발명의 인공 전사 인자의 효과적인 양은 치료될 질병의 유형에 따르며, 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이터, 및 투여 방식에 따른다. 눈에 투여하는 경우, 매달 0.5 내지 1 mg를 유리체 주입하는 것이 바람직하다. 전신 적용의 경우, 매달 10 mg/kg 주사하는 것이 바람직하다. 또한, 눈의 유리체 내로 서방 주입하는 것이 바람직하다.
또한, 본 발명은 글루코코르티코이드 수용체의 수준을 낮추거나 증가시기기 위해 글루코코르티코이드 수용체의 리간드에 대한 세포 반응 영향에 사용하기 위해, 그리고 글루코코르디코이드에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 글루코코르티코이드 수용체에 관한 인공 전사 인자에 관한 것이다.
마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 글루코코르티코이드 수용체의 리간드에 의해 조절되는 질병 치료 방법에 관한 것이다. 고려되는 질병은 글루코코르티코이드 저항, II 형 당뇨병, 비만, 관상 동맥 경화증, 관상 동맥 질환, 천식, 소아 지방 변증, 홍 반성 낭창, 우울증, 스트레스 및 신장 증후군이다. 본 발명의 인공 전사 인자의 효과적인 양은 치료될 질병의 유형에 따르며, 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이터, 및 투여 방식에 따른다. 눈에 투여하는 경우, 매달 0.5 내지 1 mg를 유리체 주입하는 것이 바람직하다. 전신 적용의 경우, 매달 10 mg/kg 주사하는 것이 바람직하다. 또한, 눈의 유리체 내로 서방 주입하는 것이 바람직하다.
또한, 본 발명은 안드로겐 수용체의 수준을 낮추거나 증가시기기 위해 안드로겐 수용체의 리간드에 대한 세포 반응 영향에 사용하기 위해, 그리고 안드로겐 수용체 리간드에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 안드로겐 수용체에 관한 인공 전사 인자에 관한 것이다.
마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 안드로겐 수용체의 리간드에 의해 조절되는 질병 치료 방법에 관한 것이다. 고려되는 질병은 전립선 암, 남성 유방암, 난소 암, 결장 직장암, 자궁 내막 암, 고환암, 관상 동맥 질환, 유형 I 당뇨병, 당뇨 망막 병증, 비만, 안드로젠 불감 증후군, 골다공증, 골관절염, 타입 II 당뇨병, 알츠하이머 병, 편두통, 주목 결핍 과잉 행동 장애, 우울증, 정신 분열증, 무정자증, 자궁 내막증, 케네디의 척추 및 안구 위축이다. 본 발명의 인공 전사 인자의 효과적인 양은 치료될 질병의 유형에 따르며, 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이터, 및 투여 방식에 따른다. 눈에 투여하는 경우, 매달 0.5 내지 1 mg를 유리체 주입하는 것이 바람직하다. 전신 적용의 경우, 매달 10 mg/kg 주사하는 것이 바람직하다. 또한, 눈의 유리체 내로 서방 주입하는 것이 바람직하다.
또한, 본 발명은 에스트로겐 수용체의 수준을 낮추거나 증가시기기 위해 에스트로겐 수용체의 리간드에 대한 세포 반응 영향에 사용하기 위해, 그리고 에스트로겐 수용체 리간드에 의해 조절되는 질병의 치료에 사용하기 위해, 상기 언급된 에스트로겐 수용체에 관한 인공 전사 인자에 관한 것이다.
마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 에스트로겐 수용체의 리간드에 의해 조절되는 질병 치료 방법에 관한 것이다. 고려되는 질병은 뼈 암, 유방암, 대장 암, 자궁 내막 암, 전립선 암, 자궁암, 알콜 중독, 편두통, 대동맥 동맥류, 심근 경색, 대동맥 판막 경화증, 심혈관 질환, 관상 동맥 질환, 고혈압, 심 부정맥 혈전증에 대한 감수성, 그레이브스 병 관절염, 배수 값 경화증, 간경변, 간염 B, 만성 간 질환, 담즙, hypospadias, 비만, 골관절염, 골감소증, 골다공증, 알츠하이머 병, 파킨슨병, 편두통, 현기증, 신경성 식욕 부진, 주의력 결핍 과잉 행동 장애, 치매, 우울증, 정신병, 자궁 내막증 및 불임이다. 본 발명의 인공 전사 인자의 효과적인 양은 치료될 질병의 유형에 따르며, 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이터, 및 투여 방식에 따른다. 눈에 투여하는 경우, 매달 0.5 내지 1 mg를 유리체 주입하는 것이 바람직하다. 전신 적용의 경우, 매달 10 mg/kg 주사하는 것이 바람직하다. 또한, 눈의 유리체 내로 서방 주입하는 것이 바람직하다.
또한, 본 발명은 불충분한 유전자 생산 발현에 의해 야기되는 병적 표현형을 완화시기기 위해 생리학적 수준으로 유전자 생산을 복원하는데 사용하기 위한, 상기 언급된 단상부족성 유전자의 프로모터 영역을 표적하여 조합된 인공 전사 인자에 관한 것이다. 마찬가지로, 본 발명은 단상부족성 유전자 프로모터에 관한 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 단상부족성에 의해 야기되거나 조절되는 질병 치료 방법에 관한 것이다.
본 발명에서 고려되는 질병은 Leri-Weill의 연골골형성이상(dyschondrosteosis), TDP43 봉입체를 가지는 측두엽 엽성 변성, Kleefstra 증후군, 디조지 증후군, 신경 섬유종증 타입 I, 피트-홉킨스(Pitt-Hopkins) 증후군, 소두증을 가진 악안면골형성부전(mandibulofacial dysostosis), Williams-Beuren 증후군, 상 염색체 우성 Ehlers-Danlos 증후군 유형 IV, sepiapterin reductase 결핍으로 인한 도파 반응성의 이긴장증(dopa-responsive dystonia), 안피부백피증(oculocutaneous albinism) II 형, Smith-Magenis 증후군, 부갑상선 기능 저하증, 감각 신경성 난청과 신장 질환 (HDR), Stickler 증후군 유형 I, Mowat-Wilson 증후군, 소안구증 증후군(syndromic Microphthalmia) 3, Ehlers-Danlos 증후군 유형 III, 무 홍채증, 가상피소체기능저하(pseudohypoparathyroidism) 유형 IA, 초기 소아의 간질성 뇌질환(early infantile epileptic encephalopathy) 4, 피부 취약성-털이 머리 증후군(skin fragility-woolly hair syndrome), Miller-Dieker 뇌회결손 증후군(lissencephaly syndrome), Wolf-Hirschhorn 증후군, 모발비지절증후군(trichorhinophalangeal syndrome) 유형 I, otodental 이형성증(dysplasia), 결손증(coloboma)과 otodental 증후군, 근긴장성 이영양증 1, Treacher-Collins 증후군 1, 가족 여드름 inversa 1, Ehlers-Danlos 증후군 유형 I, 단지증-정신 지체 증후군(brachydactyly-mental retardation syndrome), velocardiofacial 증후군, Ulnar-Mammary 증후군, campomelic 이형성증, 초기 소아 간질성 뇌질환 5, Koolen-De Vries 증후군, 완전전뇌증(holoprosencephaly) 5, syndromic 소안 구증 6, Dravet 증후군, GLUT1 결핍 증후군 1, 뇌 철 축적 신경 변성 3, 상 염색체 열성 청소년 파킨슨병(autosomal recessive juvenile Parkinson disease) 2, synpolydactyly 1, 대동맥판상부협착증(supravalvular aortic stenosis), 지배적 시신경 위축(dominant optic atrophy) 1, 카니 복합체(Carney complex) 타입 1, Pallister-Hall 증후군, Holt-Oram 증후군, 알파 지중해 빈혈/정신 지체 증후군, 발작, 신생아 가족 양성(benign familial neonatal) 1, alagille 증후군 1, 단지증 C 형, 골수성 악성 종양 관련 가족 혈소판 장애, 췌장 부전 및 선천성 심장 결함, 텔로미어 관련 폐 섬유증 및/또는 골수 장애 1, 경상 운동(mirror movements) 2, 음성 언어 장애 1, 상 염색체 우성 청각 장애 9, Kenny-Caffey 증후군 제 1 형, 운동 실조 - 모세 혈관 확장(ataxia-telangiectasia), 두정공(parietal foramina), 페인 골드 증후군(Feingold syndrome) 1, 손톱 슬개골 증후군(nail-patella syndrome), 상 염색체 우성 정신 지체 1, holoprosencephaly 3, 긴 뼈 및/또는 미러 이미지 다지증의 결핍 또는 결핍 없는 선천성 내반족(congenital clubfoot), Sotos 증후군 1, Loeys-Dietz 증후군 유형 4, 특발성 기저 신경절 석회화 3, trigonocephaly 2, centronuclear 근육 병증 3, 소뇌성 운동 실조 또는 없는 인지 장애, 가족 부분 지방 이상증 유형 4, 정중 신경의 mononeuropathy, Waardenburg 증후군 형 4C, Waardenburg 증후군 형 4B, 비 전형적 용혈성 요독 증후군 5, 상 염색체 우성 경련 하반신 마비 42, 가성상피소체기능저하증(pseudohypoparathyroidism), 상 염색체 우성 경련 하반신 마비 31, 미토콘드리아 DNA의 결실을 가진 지배적 진보적 외부 안근 마비 염색체(autosomal dominant progressive external ophthalmoplegia) 4, 척수 소뇌성 운동 실조 27, Charcot-Marie-tooth 질환 유형 2A2, 상 염색체 우성 청각 신경 병증 1, synpolydactyly 2, 지대근이영양증(limb-girdle muscular dystrophy) 1C, 뇌회결손(lissencephaly) 1, 척수 소 뇌성 운동 실조(spinocerebellar ataxia) 15, Ehlers-Danlos 유사 증후군, 유전성 운동 및 감각 신경 병증 형 IIc 형, 단신 얼굴 이형증 및 발달 지연을 가진 털이 많은 팔꿈치, Axenfeld-Rieger 증후군 유형 3, 발작성 무도병아데토시스(choreoathetosis)와 가족 유아 경련, 급성 골수성 백혈병, Charcot-Marie-tooth 질환 유형의 2D, 감각 신경성 난청을 가진 선천성 백내장, 저신장과 정신 지체를 가진 다운 증후군 유사 안면 외양, 상 염색체 우성 청각 장애 5, 백내장 또는 없이 hyperferritinemia, 사안열(oblique facial clefting) 1, 상 염색체 우성 청각 장애 2A, 초기 소아 간질성 뇌질환 1, X가 결합된 자폐증에 대한 감수성 2, 어셔 증후군 IIIA 형, 혈소판 감소증 부재중 반경 증후군(thrombocytopenia-absent radius syndrome), 열성 Robinow 증후군 염색체, 폐 혈관의 오정렬 폐포 모세 혈관 이형성증, 탄력섬유성가황색종(pseudoxanthoma elasticum), 가족성 과잉 insulinemic 저혈당증(familial hyper insulinemic hypoglycemia) 1, 울리히 선천성 근육위축병(Ullrich congenital muscular dystrophy), 이미노글리신뇨증(iminoglycinuria), 전하 증후군(Charge syndrome), 윌름 종양, 무 홍채 증, 비뇨 생식기 기형 및 정신 지체 증후군, 팔로의 4 징후(tetralogy of Fallot), 상 염색체 우성 경련 하반신 마비 4, 가족 진보적인 피부 경화증, 크레스트 증후군, 상 염색체 우성 Emery-Dreifuss 근육 영양 장애 2, 눈물샘과 침샘의 무형성, 망막 모세포종, Dowling-Degos 질환, 원발성 폐고혈압(primary pulmonary hypertension) 1, Currarino 증후군, 성례 부전 증후군, Prader-Willi 증후군, Greig cephalopolysyndactyly 증후군, 소아성 대장 용종증/유전성출혈성모세혈관확장증(hereditary hemorrhagic telangiectasia syndrome), Piebald trait, 지대근이영양증(limb-girdle muscular dystrophy) 1B, Bethlem의 근육 병증, Cowden 병, 마판 증후군, 신장 마그네슘 결핍증 2, 맥락망막질환 또는 없이 소두증, 림프 부종 또는 식도암과 정신 지체의 각화 과다증 (Tylosis), 가부키 증후군 1, 야콥 증후군, 횡격막 탈장, 선천성 하시모토 갑상선염, 개방각 녹내장 1, Beckwith-Wiedemann 증후군, DOPA 응답 근육 긴장 이상, 에피소드 kinesigenic 운동 장애 1, 치아 분화의 주요 실패, Darier-White 질환, 상 염색체 우성 커티스의 laxa 1, Cornelia De Lange 증후군 1, 쇄골두개형성부전증(cleidocranial dysplasia), 비정형성 틈(orofacial cleft) 1, Van Der Woude 증후군 1, 가족성섬유성이형성증(cherubism), 대뇌 해면 기형(cerebral cavernous malformations), 비후형심장근육병증(familial hypertrophic cardiomyopathy) 4, cardiofaciocutaneous 증후군, 단지증 D 형, 기저 세포 모반 증후군, 연골 무형성증, 두정공(parietal foramina) 2, Potocki-Shaffer 증후군, 상염색체성 우성 선천성 각하 이상증(autosomal dominant congenital dyskeratosis) 2, 언어 장애 및 자폐증 특징을 가진 정신 지체, T 세포 면역 결핍을 가지는 상염색체 우성 지한제 외 배엽 형성 장애, 부 신피질 호르몬 결합 글로불린 결핍, 무도병아데토시스(choreoathetosis), 갑상선 기능 저하증과 신생아 호흡 곤란, 일차 보효소 Q10 결핍 1, Duane-Radial Ray 증후군, 가족성 편마비 편두통 2, 경상 운동 1, Nager 형 얼굴말단뼈발생이상 1, 장척 각화증의 반점 형 IA, 및 후각 상실증 또는 없는 저고나도트로핀성성기능저하(hypogonadotropic hypogonadism)이다.
또한, 본 발명은 OPA1 생산 증가에 사용하기 위해, OPA1에 의한 질병의 치료에 사용하기 위해, 구체적으로는 운 질병의 치료에 사용하기 위해 상기 설명된 것과 같은 OPA1 프로모터에 관한 인공 전사 인자에 관한 것이다. OPA1에 의해 조절되는 질병은 상 염색체 우성 시신경 위축(autosomal dominant optic atrophy), 상 염색체 우성 시신경 위축 플러스(autosomal dominant optic atrophy plus)뿐만 아니라, 정상 안압 녹내장(normal tension glaucoma)이다.
마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 OPA1에 의해 영향받는 질병 치료 방법에 관한 것이다. 구체적으로, 본 발명은 정상 안압 녹내장 또는 지배적 시신경 위축과 관련된 신경 퇴행을 치료하는 방법에 관한 것이다. 본 발명의 인공 전사 인자의 효과적인 양은 치료될 질병의 유형에 따르며, 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이터, 및 투여 방식에 따른다. 눈에 투여하는 경우, 매달 0.5 내지 1 mg를 유리체 주입하는 것이 바람직하다. 전신 적용의 경우, 매달 10 mg/kg 주사하는 것이 바람직하다. 또한, 눈의 유리체 내로 서방 주입하는 것이 바람직하다.
또한, 본 발명은 TGFbR1의 생산을 감소거나 증가시기기 위해 TGFbR1에 의해 영향 받는병리학적 과정의 치료에 사용하기 위해, 구체적으로 눈에서 상기 병리학적 과정의 치료에 사용하기 위해, 상기 언급된 TGFbR1 프로모터에 관한 인공 전사 인자에 관한 것이다. TGFbR1에 의해 조절되는 병리학적 과정은 눈 수술 후 적응되지 않는 상처 치유이다.
마찬가지로, 본 발명은 이를 필요로 하는 환자에게 본 발명의 인공 전사 인자의 약학적으로 유효한 양의 투여를 포함하는 TGFBR1에 의해 영향받는 질병 치료 방법에 관한 것이다. 구체적으로, 본 발명은 정상 안압 녹내장 또는 지배적 시신경 위축과 관련된 신경 퇴행을 치료하는 방법에 관한 것이다. 본 발명의 인공 전사 인자의 효과적인 양은 치료될 질병의 유형에 따르며, 종, 나이, 체중, 및 개별 상태, 개별 약동학 데이터, 및 투여 방식에 따른다. 눈에 투여하는 경우, 매달 0.5 내지 1 mg를 유리체 주입하는 것이 바람직하다. 전신 적용의 경우, 매달 10 mg/kg 주사하는 것이 바람직하다. 또한, 눈의 유리체 내로 서방 주입하는 것이 바람직하다.
식물에서 인공 전사 인자의 사용
또한, 본 발명은 유전자 생성물 생성을 증가시키기 위한 식물 프로모터를 표적하는 인공 전사 인자의 용도에 관한 것이다. 바람직하게는, 인공전사 인자를 암호화하는 DNA는 식물-형질전환용 미생물 또는 식물의 형질전환을 위해 벡터로 복제된다. 대안적으로, 인공 전사 인자는 식물에 대해 국소적 적용을 위한 적절한 조성물에 적용된다.
비-인간 동물에서 인공 전사 인자의 용도
또한, 본 발명은 유전자 생성물 생성을 향상시키기 위해, 단상부족성인 비-인간 동물 프로모터를 표적하는 인공 전사 인자의 용도에 관한 것이다. 바람직하게는, 인공 전사 인자는 이를 필요로 하는 비-인간 동물에 국소적 적용을 위한 적합한 조성물에 직접적으로 적용한다.
실험예
DNA 플라스미드의 클로닝
모든 클로닝 단계에 대하여, 제한효소(restriction endonucleases) 및 T4 DNA 연결효소(T4 DNA ligase)는 NEW England Biolabs로부터 구입하였다. Shrimp Alkaline Phosphatase(SAP)은 Promega에서 구입하였다. 고-효율의 Platinum Pfx DNA 폴리머라제(Invitrogen)은 모두 표준의 PCR 반응에 적용하였다. DNA 단편(fragments) 및 플라스미드(plasmids)는 NucleoSpin Gel 및 PCR Clean-up kit, NucleoSpin Plasmid kit, 또는 NucleoBond Xtra Midi Plus kit(Macherey-Nagel)를 사용하여 제조사의 지시를 따라 분리하였다. 올리고뉴클레오티드(oligonucleotides)는 Sigma-Aldrich로부터 구매하였다. 모든 새로 제조한 플라스미드의 적절한 DNA 염기서열은 염기서열분석(Microsynth)에 의해 검증하였다.
Yeast one hybrid 에 대한 육합체(hexameric)의 아연 집게( zinc finger ) 단백질 라이브러리의 클로닝
GNN 및/또는 CNN 및/또는 ANN 결합 아연 집게(ZF) 분자들을 포함하는 육합체의 아연 집게 단백질 라이브러리는 하기의 개선점을 갖는 Gonzalez B. 등, 2010, Nat Protoc 5, 791-810을 따라서 클로닝하였다. GNN, CNN 및 ANN ZF 분자들을 암호화하는 DNA 염기서열은 합성된 후, pUC57(GenScript)에 삽입되어 각각 pAN1049(서열번호 264), pAN1073(서열번호 265) 및 pAN1670(서열번호 266)을 제조하였다. 아연 집게 단백질(ZFP) 라이브러리의 단계적인 조립은 pBluescript SK(+) 벡터에서 수행하였다. 비-기능적인 단백질로 이끄는 각각의 개별적인 클로닝 단계동안 다수의 ZF 모듈의 삽입을 피하기 위하여, pBluescript(및 1ZFP, 2ZFPs, 또는 3ZFPs를 포함하는 유도된 생성물들) 및 pAN1049, pAN1073, 또는 pAN1670은 먼저 하나의 제한효소와 함께 배양하였고 그런 다음 SAP를 처리하였다. 효소들은 두번째 제한효소를 첨가하기 전에 NucleoSpin Gel 및 PCR Clean-up 키트를 사용하여 제거하였다.
pBluescript-1ZFPL의 클로닝은 5㎍의 pBluescript를 Xhol, SAP 및 그 후에 Spel로 처리하는 것으로 수행하였다. 삽입체는 10㎍의 pAN1049(16개의 서로 다른 GNN ZF 모듈을 방출) 또는 pAN1073(15개의 서로다른 CNN ZF 모듈을 방출) 또는 pAN1670(15개의 서로 다른 ANN ZF 모듈을 방출)을 Spel, SAP 및 그 후 Xhol을 배양하는 것으로 제작하였다. pBluescript-2ZFPL 및 pBluescript-3ZFPL의 제작을 위해성, 7㎍의 pBluescript-1ZFPL 또는 pBluescript-2ZFPL은 Agel로 절단하고, 탈인산화(dephosphorylated)하였고, Spel로 절단하였다. 삽입체들은 각각 10㎍ pAN1049 또는 pAN1073 또는 pAN1670에 Spel, SAP, 및 그 후 Xmal을 적용하여 제조하였다. pBluescript-6ZFPL의 클로닝은 14㎍의 pBluescript-3ZFPL을 Agel, SAP을 처리하여 수행하였고, 그런 다음 절단된 벡터를 얻기 위하여 Spel을 처리하여 제조하였다. 3ZFPL 삽입체는 20㎍의 pBluescript-3ZFPL을 Spel, SAP, 및 그 후 Xmal을 함께 배양하는것으로부터 분리하였다.
하나, 둘, 및 세개의 ZFPs를 포함하는 라이브러리에 대한 접합(ligation) 반응은 총 20㎕의 부피에 200 ng 절단 벡터, 400 U T4 DNA 접합제를 사용하여 삽입체:벡터의 3:1 몰 비율로 정하여 실온(room temperature; RT)에서 하루 동안 수행하였다. 열 개의 20㎕로 나눠지는, 총 200㎕ 부피에 있는 2000 ng pBluescript-3ZFPL, 500 ng 3ZFPL 삽입체, 4000 U T4 DNA 접합제를 포함하는 육합체의 아연 집게 단백질 라이브러리의 접합 반응은 RT에서 하루 동안 배양하였다. 접합 반응의 부분은 각 라이브러리에 필요한 클론의 갯수에 따라 다양한 방법으로 대장균(Escherichia coli)에 형질전환하였다. pBluescript-1ZFPL 및 pBluescript-2ZFPL의 제조를 위하여, 접합 반응의 3㎕는 E. coli NEB 5-알파의 열 충격 형질전환(heat shock transformation)(EquiBio의 EasyjecT Plus electroporator 또는 Eppendorf의 Multiporator, 2.5 kV 및 Bio-Rad의 25 μF, 2 mm electroporation cuvettes)에 직접적으로 사용하였다. pBluescript-6ZFP 라이브러리의 접합 반응은 NucleoSpin Gel 및 PCR Clean-up 키트에 적용하였고, DNA는 15㎕의 탈염수(deionized water)에 용출하였다. 약 60 ng의 탈염 DNA는 50㎕의 NEB 10-베타 전기만능(electrocompetent) E.coli(New England Biolabs)와 혼합하였고, 전기천공법(elecroporation)은 EasyjecT Plus 또는 Multiporator, 2.5 kV, 25μF 및 2 mm 전기천공법 cuvettes을 사용하여 제조사의 지시를 따라 수행하였다. 다수의(multiple) 전기천공법은 각 라이브러리에 대해 수행하였고 세포는 라이브러리의 크기를 증가시킨다음 직접적으로 합쳐졌다. 열 충격 형질전환 또는 전기천공법 이후에, SOC 배지를 박테리아에 적용하였고, 37℃ 및 250 rpm에서 1시간동안 배양한 후, 30㎕의 SOC 배양액은 단계적으로 희석하는데 사용하였고, 암피실린(ampicillin)을 포함하는 LB 배양접시(plates)에 도말하였다. 다음 날, 획득한 라이브러리 클론의 총 갯수를 측정하였다. 게다가, 각 라이브러리의 열 개의 클론은 플라스미드 DNA를 분리하기위해 및 제한효소 절단에 의한 삽입체의 융합을 확인하기 위하여 선택하였다. 상기 플라스미드의 최소 세 개는 라이브러리의 다양성을 검증하기 위하여 서열분석을 하였다. 남아있는 SOC 배양액은 암피실린을 포함하는 100ml의 LB 배재에 이동하였고 37℃ 및 250 rpm에서 하루동안 배양하였다. 이러한 세포는 각 라이브러리에 대한 플라스미드 Midi DNA를 준비하는데 사용하였다.
Yeast one hybrid 스크리닝을 위하여, 육합체의 아연 집게 단백질 라이브러리는 경쟁가능한 먹이(prey) 벡터로 이동하였다. 이 목적을 위하여, pGAD10(Clontech)의 다수의 클로닝 위치는 벡터를 XhoI / EcoRI으로 자르고 어닐링된(annealed) 올리고뉴클레오티드 OAN971(TCGACAGGCCCAGGCGGCCCTCGAGGATATCATGATG ACTAGTGGCCAGGCCGGCCC, 서열번호 267) 및 OAN972 (AATTGGGCCGGC CTGGCCACTAGTCATCATGATATCCTCGAGGGCCGCCTGGGCCTG, 서열번호 268)의 삽입에 의하여 변형하였다. 결과적으로 pAN1025 벡터(서열번호 269)는 잘려지고 탈인산화어, 6ZFP 라이브러리 삽입체가 XhoI / Spel에 의해 pBluescript-6ZFPL로부터 분리되었다. 접합 반응 및 NEB 10-베타 전기만능 E. coli로의 전기천공법은 상기에 기술된 pBluescript-6ZFP 라이브러리와 같이 수행하였다.
개선된 yeast one hybrid 스크리닝을 위해서, 육합체의 아연 집게 라이브러리는 개선된 먹이 벡터 pAN1375(서열번호 270)으로 이동하였다. 이 먹이 벡터는 하기의 방법으로 제조하였다: pRS315(서열번호 271)은 Apal / Narl로 절단하였고 어닐링된 OAN1143(CGCCGCATGCATTCATGCAGGCC, 서열번호 272) 및 OAN1144 (TGCATGAATGCATGCGG, 서열번호 273)가 삽입되어 pAN1373(서열번호 274)을 만들었다. pAN1025로부터의 Sphl 삽입체는 Sphl로 절단된 pAN1373에 접합하여 pAN1375를 획득하였다.
더욱 개선된 yeast one hybrid 스크리닝을 위하여, 육합체의 아연 집게 라이브러리는 개선된 먹이 벡터 pAN1920(서열번호 275)로 이동하였다.
더더욱 개선된 yeast one hybrid 스크리닝을 위하여, 육합체의 아연 집게 라이브러리는 먹이 벡터 pAN1992(서열번호 276)으로 삽입하였다.
Yeast one hybrid 스크리닝을 위한 미끼( bait ) 플라스미드의 클로닝
각각의 미끼 플라스미드를 위하여, 가운데에 18bp의 잠재벅인 인공적 전사 인자 타겟 위치를 갖고있는 60bp 염기서열을 선별하였고 제한 분석(restriction analysis)를 위한 Ncol 위치를 포함하였다. 올리고뉴클레오타이드는 HindIII / XhoI으로 절단된 pABAi(Clontech)으로 직접적인 접합이 가능하도록 하는 5'HindIII 및 3'XhoI 위치를 생성하도록 하는 방법으로 디자인하고 어닐링하였다. NcoI로의 절단 및 염기서열 분석은 미끼 플라스미드의 조립을 확인하기 위하여 사용하였다.
효모 균주 및 배지
사카로미세스 세레비지애(Saccharomyces cerevisiae) Y1H Gold는 Clontech로부터 구입하였고, YPD 배지 및 YPD 아가(agar)는 Carl Roth로부터 구입하였다. 합성된 drop-out(SD) 배지는 20 g/l glucose, 6.8 g/l Na2HPO4 ·2H2O, 9.7 g/l NaH2PO4 ·2H2O (모두 Carl Roth), 1.4 g/l 효모 합성 drop-out 배지 첨가물(supplements) , 6.7 g/l 효모 질소 염기, 0.1 g/l L tryptophan, 0.1 g/l L leucine, 0.05 g/l L-adenine, 0.05 g/l L-histidine, 0.05 g/l uracil (모두 Sigma-Aldrich)를 포함하였다. 우라실(uracil), SD-L을 제외한 모든 성분들을 포함하는 SD-U 배지, L-leucine을 제외하고 SD-L 배지를 준비하였다. SD 아가 배양접시는 소듐 포스페이트(sodium phosphate)를 포함하지 않았고, 16g/l Bacto Agar(BD)를 포함하였다. Aureobasidin A(AbA)는 Clontech에서 구입하였다.
미끼 효모 균주의 준비
각각의 미끼 플라스미드의 5 ㎍은 총 20 ㎕부피에서 BstBl로 직선화(linearized)하였고, 반응 혼합물의 절반은 S.세레비지애 Y1H Gold의 열 충격 형질전환에 직접적으로 사용하였다. 효모 세포는 형질전환 전날에 5 ml YPD 배지에 접종하는 데 사용하였고 실온의 회전기기(roller)에서 하루 동안 배양하였다. 이 전-배양액의 1 ml는 새로운 YPD 배지로 1:20으로 희석하였고, 30℃, 225 rpm에서 2-3시간 동안 배양하였다. 각각의 형질전환 반응 1 OD600 세포들은 원심분리에 의해 수확하였고, 효모 세포들은 1 ml 멸균수로 한번 세척한 다음, 1 ml TE/LiAc (10 mM Tris/HCl, pH 7.5, 1 mM EDTA, 100 mM lithium acetate)로 한번 세척하였다. 최종적으로, 효모 세포들은 50 ㎕ TE/LiAc에 재용해하였고 50 ㎍의 연어 시료(salmon testes)로부터의 단일 가닥 DNA (Sigma-Aldrich), 10 ㎕의 BstBI-직선화된 미끼 플라스미드(상기), 및 300 ㎕ PEG/TE/LiAc(10 mM Tris/HCl, pH 7.5, 1 mM EDTA, 100 mM lithium acetate, 50 % (w/v) PEG 3350)로 혼합하였다. 세포 및 DNA는 실온에서 20분 동안 회전기에서 배양하였고, 그런 다음 15분 동안 42℃ 수조에 넣었다. 결과적으로, 효모 세포들은 원심분리에 의해 수집하였고 100 ㎕의 멸균수에 재용해하였으며, SD-U 아가 배양접시에 도말하였다. 30℃에서 3일간의 배양 후에 각 형질전환 반응으로부터 SD-U에서 자란 여덟 개의 클론을 선택하였고 aureobasidin A(AbA)에 대한 이들의 민감성을 분석하였다. 전-배양액은 실온의 회전기에서 하루 동안 배양하였다. 각 배양액에 대하여, OD600측정하였고, OD600=0.3을 멸균수를 이용하여 조절하였다. 첫 번째의 희석으로부터 다섯개의 추가적인 1:10 희석 단계를 멸균수로 준비하였다. 각 희석 단계의 5 ㎕의 각 클론을 SD-U, SD-U 100 ng/ml AbA, SD-U 150 ng/ml AbA, 및 SD-U 200 ng/ml AbA를 포함하는 아가 배양접시에 점 형태로 도말하였다. 30℃에서 3일 동안의 배양 후에, SD-U에서 잘 자라고 AbA에 가장 민감한 세 개의 클론을 선택하여 추가적인 분석을 하였다. 효모 게놈으로의 미끼 플라스미드의 안정적인 일체화(integration)는 Matchmaker Insert Check PCR Mix 1(Clontech)를 사용하여 제조사의 지시를 따라 검증하였다. 세 개의 클론 중 하나는 그 후의 Y1H 스크리닝을 위하여 사용하였다.
육합체 아연 집게 단백질 라이브러리를 갖는 미끼 효모 균주의 형질전환
전-배양액의 효모 미끼 균주의 약 500 ㎕은 1 L YPD 배지로 희석하였고 30℃, 225 rpm에서 OD600=1.6-2.0(약 20 시간)이 될 때까지 배양하였다. 세포는 스윙-아웃 회전기(swing-out rotor)에서 원심분리에 의해 수집하였다(5 분, 1500×g, 4℃). 전기만능 세포의 준비는 Benatuil L. 등., 2010, Protein Eng Des Sel 23, 155-159을 따라 수행하였다. 각 형질전환 반응에 대해서, 400 ㎕의 전기만능 미끼 효모 세포는 6ZFP 라이브러리를 암호화하는 1 ㎍ 먹이 플라스미드와 혼합하였고 3분 동안 얼음에서 배양하였다. 상기 세포-DNA 현탁액은 미리-차갑게한 2 mm 전기천공 cuvette으로 이동하였다. 다수의 전기천공 반응(EasyjecT Plus electroporator 또는 Multiporator, 2.5 kV 및 25 μF)은 모든 효모 세포 현탁액이 형질전환될 때까지 수행하였다. 전기천공 효모 세포가 YPD: 1M 소르비톨(sorbitol)의 1:1 혼합의 100 ml로 이동시킨 다음 30℃, 225 rpm에서 60분 동안 배양하였다. 세포는 원심분리에 의해 수확하였고 SD-L 배지의 1-2 ml에 재용해하였다. 200 ㎕의 부분표본(aliquots)은 1000-4000 ng/ml AbA를 포함하는 15 cm SD-L 아가 배양접시에 도말하였다. 게다가, 세로 현택액의 50 ㎕는 1/100 및 1/1000 희석액을 만드는 데 사용하였고, 50 ㎕의 비희석(undiluted) 및 희석된 세포는 SD-L에 도말하였다. 모든 배양접시는 30℃에서 3일동안 배양하였다. 획득한 클론의 총 갯수는 희석된 형질전환체(transformants)를 갖는 배양접시로부터 계산하였다. 비희석된 세포를 갖는 SD-L 배양접시가 모든 형질전환체의 성장을 나타내는 반면, AbA-포함된 SD-L 배양접시는 오직 먹이 6ZFP가 그것의 미끼 타겟 위치에 성공적으로 결합하였을 때의 콜로니 형성에 기인한다.
6 ZFP -암호화 먹이 플라스미드의 양성적 작용 및 회복의 검증
초기의 분석을 위해서, 40개의 좋은-크기의 콜로니를 높은 AbA 농도를 갖는 SD-L 배양접시로부터 선택하였고 효모 세포들은 단일 콜로니를 획득하기 위하여 1000-4000 ng/ml AbA를 갖는 SD-L에 두 번 도말하였다. 각각의 콜론에 대하여, 한 개의 콜로니는 5 ml SD-L 배지에 접종하는 데 사용하였고 세포는 실온에서 하루동안 배양하였다. 다음 날, OD600=0.3을 멸균수로 조절하였고, 다섯 개의 추가적인 1/10 희석물을 준비한 뒤, 각 희석 단계의 5 ㎕를 SD-L, SD-L 500 ng/ml AbA, 1000 ng/ml AbA, SD-L 1500 ng/ml AbA, SD-L 2000 ng/ml AbA, SD-L 2500 ng/ml AbA, SD-L 3000 ng/ml AbA, 및 SD-L 4000 ng/ml AbA 배양접시에 에 점 형태로 도말하였다. 클론은 높은 AbA 농도에서 자랄 수 있는 능력에 따라 순위를 매겼다. 초기의 SD-L 전-배양액의 5 ml에서 가장 잘 자란 콜로니로부터 세포를 회전하여 침전시키는 데 사용하였고, 100 ㎕ 물 또는 남겨진 배지에 재용해하였다. 50 U lyticase(Sigma-Aldrich, L2524)를 첨가한 후, 세포는 수평적 쉐이커(horizontal shaker)에서 37℃, 330 rpm으로 몇 시간동안 배양하였다. 생성된 스페로플라스트(spheroplasts)는 10 ㎕의 20%(w/v) SDS 용액에 의해 용리하였고, 1 분동안 격렬한 vortexing으로 혼합한 후, -20℃에서 최소 1시간 동안 냉동하였다. 그런 다음, NucleoSpin Plasmid kit의 A1 완충용액 250 ㎕ 및 유리 비드(Sigma-Aldrich, G8772)의 한 개의 스파출라 팁(spatula tip)을 첨가하였고, 튜브를 1분 동안 격렬하게 vortexing 하였다. 플라스미드 분리는 NucleoSpin Plasmid kit의 A2 완충용액 250 ㎕의 첨가로 더 개선하였고, 기본적인 NucleoSpin Plasmid kit 프로토콜을 진행하기 전에 실온에서 최소 15분간 배양하였다. 30 ㎕의 용리 완충용액으로 용리한 후, 5㎕의 플라스미드 DNA를 E. coli DH5 알파로 열 충격 형질전환에 의해 형질전환하였다. 두 개의 개별적인 콜로니를 암피실린-포함된 LB 배양접시로부터 선별하였고, 플라스미드를 분리하여 라이브러리 삽입체를 서열분석하였다. 획득한 결과는 각 타겟 위치에 대한 6ZFP 사이의 일치 서열(consensus sequences)에 대해 분석하였다.
결합되고 분비된 루시퍼라제 ( luciferase ) 및 알카라인 포스파타제( alkaline phosphatase) 분석을 위한 유전자 프로모터의 클로닝
프로모터 영역을 포함하는 DNA 절편은 pAN1485(NEG-PG04, GeneCopeia) 또는 pAN1486(EF1a-PG04, GeneCopeia)에 클로닝하였고, 이들은 단상부족성(haploinsufficient) 유전자 프로모터의 조절 하에서 분비된 Gaussia 루시퍼라제(luciferase) 및 알카라인 포스파타제 신호에 대해 루시퍼라제의 표준화를 하도록 하는, 구성적인 CMV 프로모터의 조절 하에서 분비된 배아(embryonic)의 알카라인 포스파타제를 포함하는 리포터 플라스미드에 기인한다.
형질도입가능한( transducible ) 인공적인 전사 인자 활성을 시험하기 위한 안정한 루시퍼라제 /분비된 알카라인 포스파타제 리포터 세포주의 제조를 위한 리포터 플라스미드의 클로닝
구성적인 CMV 프로모터의 조절 하에서 분비된 알카라인 포스파타제와 함께 이합체 CMV/인공적인 전사 인자 타겟 위치 프로모터의 조절하에서 Gaussia 루시퍼라제를 포함하는 리포터 구조체를 제조하기 위하여, 인공적인 전사 인자 결합 위치를 갖는 42bp는 pAN1660(서열번호 277)로 AflIII / SpeI에 의해 클로닝하였다. 이러한 리포터 구조체들은 HEK293 Flpln TRex(Invitrogen) 세포와 같은 Flpln 위치를 포함하는 세포들로의 안정적인 융합을 위한 Flpln 위치를 갖고 있다.
포유동물의 형질전환을 위한 인공적인 전사 인자의 클로닝
Gensynthesis(GenScript)에 의해 생성되거나 또는 yeast one hybrid에 의해 선별된 polydactyl 아연 집게 단백질을 암호화하는 DNA 절편들은
관심 있는 것의 아연 집게 어레이(array), SV40 NLS, 3x myc 에피토프(epitope) 태그 및 N-말단 KRAB 도메인(pAN1255 - 서열번호 278), C-말단 KRAB 도메인(pAN1258 - 서열번호 279), SID 도메인(pAN1257 - 서열번호 280) 또는 VP64 활성 도메인(pAN1510 - 서열번호 281) 간의 융합 단백질로서 포유동물 세포에 발현하기 위한 포유동물 발현 벡터로 기본적인 방법을 사용하여 클로닝하였다.
안정적인 형질전환의 생성을 위한 플라스미드, 테트라사이클린-유도성(tetracycline-inducible) 세포는 하기의 방법으로 제조하였다: polydactyl 아연 집게 도메인, 조절 도메인(N-말단 KRAB, C-말단 KRAB, SID or VP64), SV40 NLS 및 3x myc 에피토프 태그를 포함하는 인공적인 전사 인자들을 암호화하는 DNA 절편들은 EcoRV / Notl을 사용하여 pcDNA5/FRT/TO(Invitrogen)으로 클로닝하였다.
안정적인 형질전환의 생성을 위한 플라스미드, 테트라사이클린-유도성 세포는 하기의 방법으로 제조하였다: polydactyl 아연 집게 도메인, 조절 도메인 (N-말단 KRAB, C-말단 KRAB, SID or VP64), 및 SV40 NLS를 포함하는 인공적인 전사 인자를 암호화하는 DNA 절편들은 EcoRV / AgeI를 사용하여 pAN2071 (서열번호 282)로 클로닝하였다. 이러한 인공적인 전사 인자 발현 플라스미드는 AAVS1 Left TALEN 및 AAVS1 Right TALEN (GeneCopoeia)와 함께 공동-형질전환에 의해 AAVS1 유전자 위치로의 인간 게놈으로 결합될 수 있다.
세포 배양 및 형질전환
HeLa 세포는 37℃, 5%의 CO2에서 4.5 g/l glucose, 10 % 열-비활성화된 우태아 혈청(heat-inactivated fetal bovine serum), 2 mM L-glutamine, 및 1 mM sodium pyruvate (모두 Sigma-Aldrich)가 첨가된 DMEM(Dulbecco’s Modified Eagle’s Medium)에서 배양하였다. 루시퍼라제 리포터 분석을 위하여, 7000 Hela 세포/웰은 96 웰 배양접시에 분주하였다. 다음 날, Effectene Transfection Reagent(Qiagen)를 사용하여 제조사의 지시를 따라서 공동-형질전환을 수행하였다. 인공적인 전사 인자 및 루시퍼라제를 암호화하는 플라스미드 미디 제작은 3:1의 비율로 사용하였다. 배지는 형질전환 후 6시간 및 24시간 후에 100 ㎕/웰의 새로운 DMEM으로 교체하였다.
Flp - In Tm T- Rex TM 293 발현 세포주의 생성 및 유지
안정적이고, 테트라사이클린 유도성의 Flp-InTm T-RexTM 293 발현 세포주는 Flp Recombinase-매개된 통합에 의해서 제조하였다. Flp-InTm T-RexTM 중심 키트를 사용하여, Flp-InTm T-RexTM 숙주세포주는 pFRT/lacZeo 타겟 위치 벡터 및 pcDNA6/TR 벡터를 형질전환하는 것으로 제조하였다. 유도가능한 293 발현 세포주의 생성을 위해서, 관심 있는 유전자를 포함하는 pcDNA5/FRT/TO 발현 벡터는 Flp-InTm T-RexTM 숙주세포주의 FRT 위치에서 Flp recombinase-매개된 DNA 재조합(recombination)으로 통합하였다. 안정적인 Flp-InTm T-RexTM 발현 세포주는 DMEM; 10 % Tet-FBS; 2 mM glutamine; 15 μg/ml blasticidine 및 100 μg/ml hygromycin을 포함하는 선별 배지에서 유지하였다. 유전자 발현의 유도를 위하여, 테트라사이클린은 최종 농도 1 ㎍/ml로 첨가하였다.
TALENs 를 이용한 안정적인 인공적 전사 인자를 발현하는 세포주의 생성 및 유지
테트라사이클린-유도성 프로모터의 조절 하에서 안정적으로 인공적인 전사 인자를 발현하는 세포 주를 생성하기 위하여, 세포는 Effectene(Qiagen, 형질전환 시약)을 사용하여 제조사의 지시에 따라, 관심이 있는 인공적인 전사 인자를 포함하는 pAN2071-기반의 발현 구조체 및 AAVS1 Left TALEN 및 AAVS1 Right TALEN(GeneCopoeia)로 공동-형질전환하였다. 형질전환 8시간 후에, 배양 배지는 흡입기로 제거하였고, 세포는 PBS로 세척하고 새로운 배양 배지를 첨가하였다. 형질전환 24시간 후에, 세포는 항생제가 없는 Tet-approved FBS(tetracycline free FBS, Takara)를 포함하는 배양 배지로 1:10의 비율로 나누었다. 형질전환 48시간 후에, 세포-종류 특이적인 농도에서 퓨로마이신(puromycin) 선별을 시작하였고 세포는 7-10일 동안 선별 압력하에서 유지하였다. 안정적인 세포의 콜로니를 취합하였고 선별 배지에서 유지하였다.
결합된 루시퍼라제 / SEAP 프로모터 활성 분석
HeLa 세포는 인공적인 전사 인자 발현 구조체 및 단상부족성(haploinsufficient) 유전자 프로모터의 조절 하에서 분비된 Gaussia 루시퍼라제(luciferase) 및 구성적인 CMV 프로모터 조절하에서 분비된 알카라인 포스파타제(Gaussia luciferase Glow Assay Kit, Pierce; SEAP Reporter Gene Assay chemiluminscent, Roche)를 갖는 플라스미드와 함께 공동 형질전환하였다. 형질전환 이틀 뒤에, 세포 배양 상층액을 수집하였고, 루시퍼라제 활성 및 SEAP 활성은 Secrete-Pair Dual Luminescence assay(GeneCopoeia) 또는 SEAP reporter gene assay(Roche)를 사용하여 측정하였다. 아연 집게 도메인에 있는 모든 시스테인(cysteine) 잔기가 세린(serine) 잔기로 변경되어 있는 불활성 인공 전사 인자에 대한 발현 플라스미드의 공동-형질전환을 대조군으로 제공하였다. 루시퍼라제 활성은 SEAP 활성에 대해 표준화하였고 대조군에 대한 백분율로서 표시하였다.
단백질 형질도입( transduction )을 따르는 인공적인 전사 인자 활성 평가를 위한 루시퍼라제 리포터 분석
안정적인 HEK 293 Flpln 세포는 예상되는 인공적인 전사 인자에 대한 적당한 타겟 위치를 포함하는 혼성의(hybrid) CMV 프로모터의 조절하의 Gaussia 루시퍼라제 뿐만 아니라 구성적인 CMV 프로모터의 조절하의 SEAP를 포함하는 것으로 준비하였다. HEK 293 Flpln 세포는 각각 ETRA(TS-74), ETRA(TS+50), FCER1A(TS-147), TLR4(TS-222), TGFbR1(TS-390), 또는 AR(TS-236)을 타겟하는 인공적인 전사 인자를 시험하기 위한 세포주를 제작하기 위하여 pAN1660, pAN2210(서열번호 283), pAN1705(서열번호 284), pAN2001(서열번호 285), pAN2122(서열번호 286), 또는 pAN2100(서열번호 287)로 형질전환하였다.
이러한 세포들은 연관되지 않거나 불활성화 인공적인 전사 인자를 대조군으로 사용하고, 적절한 인공적인 전사 인자(1 μM) 또는 완충용액을 갖는 OptiMem에서 2시간 동안 처리하였다. 단백질 형질도입을 따라서, 세포는 수확하였고 정상의 성장 배지로 재분주하였으며, 루시퍼라제 및 SEAp 활성을 제조사의 지시를 따라 24시간 후에 측정하였다(Gaussia Luciferase Glow Assay Kit, Thermo Scientific; SEAP Reporter Gene Assay Chemiluminescence, Roche). 루시퍼라제 값은 SEAP 활성으로 표준화하였고 100%를 맞추는 것으로 대조군 세포에 비교하였다.
정량적인 RT - PCR 에 의한 유전자 발현 수준의 결정
총 RNA는 RNeasy Plus Mini Kit (Qiagen, Hilden, Germany)를 사용하여 제조사의 지시를 따라, 세포로부터 분리하였다. 냉동 세포 침전물(pellets)은 10 μl/ml β-mercaptoethanol을 포함하는 RLT Plus Lysis 완충용액에 재용해하였다. QIAshredder 스핀 컬럼을 이용한 균질화 후, 총 세포 용해물(lysate)은 genomic DNA를 제거하기 위하여 gDNA Eliminator 스핀 컬럼으로 이동하였다. 70% 에탄올의 하나의 부피를 첨가하였고, 총 세포 용해물은 RNeasy 스핀 컬럼으로 이동하였다. 몇 번의 세척 단계 후에, RNA는 최종 30 ㎕ 부피의 RNase 무첨가 물에 용출하였다. RNA는 그 이후에 사용시까지 -80℃에서 보관하였다. cDNA의 합성은 High Capacity cDNA Reverse Transcription Kit (Applied Biosystems, Branchburg, New Jersey, USA)를 사용하여 제조사의 지시에 따라 수행하였다. cDNA 합성은 2 μl 10x 완충용액, 0.8 μl 25x dNTP Mix, 2 μl 10x RT 임의의(random) 프라이머, 1 μl Multiscribe Reverse Transcriptase 및 4.2 μl H2O를 포함하는 20 ㎕의 총 반응 부피에서 수행하였다. 10 ㎕ RNA의 최종 부피를 첨가하였고 하기 조건에서 반응을 수행하였다: 25°C에서 10분, 37°C 에서 2시간 및 85°C에서 5분간의 마지막 단계. 정량적인 PCR은 1 μl 20x TaqMan Gene Expression Master Mix, 10.0 μl TaqMan® Universal PCR Master Mix (모두 Applied Biosystems, Branchburg, New Jersey, USA) 및 8 ㎕의 H2O를 포함하는 총 20 ㎕의 반응 부피에서 수행하였다. 각 반응에 대하여, 1 ㎕의 cDNA를 첨가하였다. qPCR은 ABI PRISM 7000 Sequence Detection System (Applied Biosystems, Branchburg, New Jersey, USA)를 사용하여 하기의 조건으로 수행하였다: 50℃에서 2분간의 초기 단계를 따르는 95℃에서 10분 동안의 첫번째 변성, 그리고 95℃에서 15초 및 60℃에서 1분의 40사이클을 포함하는 그 후 단계.
박테리아 발현을 위한 인공적인 전사 인자의 클로닝
인공적인 전사 인자를 암호화하는 DNA 절편은 인공적인 전사 인자 및 TAT 단백질 형질도입 도메인 사이의 His6-태그된 융합 단백질로써 E. coli에서 발현을 위한 pET41a+(Novagen)에 기초하여 박테리아 발현 벡터 pAN983(서열번호 288)로 EcoRV/NotI으로 표준의 방법을 사용하여 클로닝하였다. 서열번호 28의 카뎁신(cathepsin B) 절단 위치를 포함하는 카뎁신 B 민감성 인공적인 전사 인자의 발현을 위하여, 인공적인 전사 인자를 암호화하는 DNA 절편은 박테리아 발현 벡터 pAN1688(서열번호 289)로 표준의 방법(EcoRV / NotI)을 사용하여 클로닝하였다. ETRA, FcER1A , TLR4 , AR , OPA1, 또는 TGFbR1을 타켓하는 BL21(DE3)와 같은 적절한 E.coli 숙주세포에 카텝신 B-민감성 형질유도성 인공적인 전사 인자의 박테리아 생성을 위한 발현 구조체는 pAN1688, pAN1880(서열번호 290), pAN1966(서열번호 291), pAN2054(서열번호 292), pAN2056(서열번호 293), pAN2058(서열번호 294), pAN2060(서열번호 295), pAN2062(서열번호 296), pAN2064(서열번호 297), pAN2104(서열번호 298), pAN2112(서열번호 299), pAN2114(서열번호 300), pAN2116(서열번호 301), pAN2132(서열번호 302), pAN2134(서열번호 303), pAN2159(서열번호 304), pAN2160(서열번호 305), pAN2161(서열번호 306), pAN2286(서열번호 307), pAN2287(서열번호 308), pAN2288(서열번호 309), pAN2289(서열번호 310), pAN2290(서열번호 311), pAN2291(서열번호 312), pAN2292(서열번호 313), pAN2293(서열번호 314), pAN2323(서열번호 315), pAN2326(서열번호 316), pAN2328(서열번호 317), pAN2331(서열번호 318), and pAN2334(서열번호 319) 이다.
인공적인 전사 인자 단백질의 생성
주어진 인공적인 전사 인자에 대한 발현 플라스미드로 형질전환된 E. coli BL21(DE3)는 100 μM ZnCl2를 첨가한 1L LB 배지에서 OD600 값이 0.8과 1 사이에 도달할 때까지 배양하였고, 1 mM IPTG를 첨가하여 두 시간동안 유도하였다. 박테리아는 원심분리로 수확하였고, 박테리아 세포 용해물은 초음파에 의해 준비하였으며, 봉입체(inclusion body)를 정제하였다. 이를 끝내기 위하여, 봉입체는 원심분리로 수집하였고(5000g, 4℃, 15분), 20 ml의 결합 완충용액(50 mM HEPES, 500 mM NaCl, 10 mM imidazole; pH 7.5)으로 세 번 세척하였다. 정제된 봉입체는 30 ml의 결합 완충용액 A(50 mM HEPES, 500 mM NaCl, 10 mM imidazole, 6 M GuHCl; pH 7.5)에서 한 시간동안 얼음에서 가용화(ionization)하였다. 가용화한 봉입체는 4℃, 13'000g에서 40분동안 원심분리하였고, 0.45 ㎛ PVDF 필터로 여과하였다. His-태그된 인공적인 전사 인자는 결합 완충용액 A 및 용리 완충용액 B(50 mM HEPES, 500 mM NaCl, 500 mM imidazole, 6 M GuHCl; pH 7.5)를 사용하여 Aktaprime FPLC (GEHealthcare)에 있는 His-Trap 컬럼으로 정제하였다. 정제된 인공적인 전사 인자를 포함하는 분획을 모은 후 전사 인자가 SID 도메인을 포함하였을 경우에는 완충용액 S (50 mM Tris-HCl, 500 mM NaCl, 200 mM arginine, 100 μM ZnCl2, 5 mM GSH, 0.5 mM GSSG, 50% glycerol; pH 7.5)에 대하여, 인공적인 전사 인자를 포함하는 KRAB 도메인에 대해서는 완충용액 K(50 mM Tris-HCl, 300 mM NaCl, 500 mM arginine, 100 μM ZnCl2, 5 mM GSH, 0.5 mM GSSG, 50% glycerol; pH 8.5)에 대해서 4℃에서 하루 동안 투석하였다. 투석 이후에, 단백질 샘플은 4℃에서 30분 동안 14'000으로 원심분리하였고, 0.22 ㎛ Millex-GV 필터 팁(Millipore)를 사용하여 여과하였다. VP64 활성화 도메인을 포함하는 인공적인 전사 인자를 위하여, 단백질은 His-Bond Ni-NTA resin (Novagen)을 사용하여 제조사의 지시를 따라 수용성 분획(결합 완충용액: 50 mM NaPO4 pH 7.5, 500 mM NaCl, 10 mM imidazole; 용리 완충용액 50 mM HEPES pH 7.5, 500 mM NaCl, 500 mM imidazole)로부터 생성하였다. 단백질은 VP64-완충용액(550 mM NaCl pH 7.4, 400 mM arginine, 100 μM ZnCl2)에 대하여 투석하였다.
ELDIA (효소- 결합된 DNA 상호작용 분석)을 사용한 인공적인 전사 인자의 DNA 결합 활성의 결정
BSA 전-봉쇄된(pre-blocked) 니켈 코팅된 배양접시(Pierce)는 세척 완충용액(25 mM Tris/HCl pH 7.5, 150 mM NaCl, 0.1% BSA, 0.05 % Tween-20)으로 세 번 세척하였다. 배양접시는 저장 완충용액에서 포화 조건(50 pmol/웰) 하에서 정제된 인공적인 전사 인자로 코팅하였고 약한 움직임과 함께 실온에서 1시간 동안 배양하였다. 세 번의 세척 단계 이후에, 어닐링된 것의 1x 10- 12 에서 5x 10-7 M, 60bp 프로모터 서열을 포함하는 바이오틴화된(biotinylated) 올리고(oligos)는 결합된 인공적인 전사 인자와 함께 비특이적인 경쟁자(연어 정자(salmon sperm)로 부터 0.1 mg/ml ssDNA, Sigma)의 존재하에서 결합 완충용액(10 mM Tris/HCl pH 7.5, 60 mM KCl, 1 mM DTT, 2% glycerol, 5 mM MgCl2 and 100 μM ZnCl2)에 실온에서 1시간 동안 배양하였다. 세척 후(5번), 웰은 실온에서 30분동안 3% BSA로 봉쇄하였다. 결합 완충용액에 있는 항-스트렙타비딘(streptavidin)-HRP을 첨가하여 실온에서 1시간 동안 두었다. 5번의 세척 단계 후, TMB 기질(Sigma)를 첨가하였고 실온에서 2 내지 30분동안 배양하였다. 반응은 TMB 정지 용액을 첨가하는 것으로 정지하였고 샘플 흡광(extinction)은 450nm에서 측정하였다. 리간드(ligand) 결합 효소 반응의 데이터 분석은 Hill을 따르는 Simga Plot V8.1을 사용하여 수행하였다.
단백질 형질 도입
세포는 약 80%의 밀집도(confluency)를 가질 때까지 배양하였고 선택적으로 37℃의 OptiMEM 또는 성장 배지에 있는 인공적인 전사 인자를 매 24시간마다 첨가하는 것과 함께, 0.01 내지 1 μM의 인공적인 전사 인자 또는 모의 대조군(mock)을 2시간 내지 120시간 처리하였다. 선택적으로, 100-500 μM의 ZnCl2를 성장 배지에 첨가하였다. 면역형광법(immunofluorescence)를 위하여, 세포는 PBS로 한번 세척하였고, 트립신화(trypsinized) 한 후, 이후의 검사를 위해 유리 커버 슬립으로 분주하였다.
면역형광법
세포는 PBS에 있는 4% 파라포름알데히드(paraformaldehyde)로 고정하였고, 15분 동안 0.15% Triton X-100으로 처리하였으며, 10% BSA/PBS로 봉쇄한 후 마우스 항-HA 항체(1:500, H9658, Sigma) 또는 마우스 항-myc(1:500, ㅡ5546, Sigma)를 이용하여 하루 동안 배양하였다. 샘플은 PBS/1%/BSA로 세 번 세척하였고, Alexa Fluor 546(1:1000, Invitrogen)에 연결되어 있는 염소 항-마우스 항체로 배양한 다음 DAPI(1 mg/ml의 1:1000dmfh 3분, Sigma)를 사용하여 반전염색(counterstained)하였다. 샘플은 형광 현미경으로 분석하였다.
웨스턴 블롯( western blotting )
단백질 수치를 측정하기 위하여, 세포는 RIPA 완충용액(Pierce)로 용리하였고 단백질 세포 용해물은 Laemmli 샘플 완충용액으로 혼합하였다. 단백질은 그들의 크기에 따라 SDS-PAGE로 분리되었고, 일렉트로블롯팅(electroblotting)으로 니트로셀룰로스(nitrocellulose) 멤브레인(membrane)에 이동하였다. 1차 항체의 검출은 홀스래디쉬 퍼록시다제(horseradish peroxidase)에 연결된 2차 항체와 발광( luminescence)-기반의 검출(ECL plus, Pierce) 또는 DyLight700 또는 DyLight800 형광에 결합한 2차 항체에 의해 수행되어 검출되었고 적외선 레이저 스캐너(infrared laser scanner)를 이용하여 정량하였다.
미토콘드리아 기능의 측정
유동 세포 분석(flow cytometric analysis)을 위하여, 처리된 세포는 10 mM EDTA/PBS로 수확하였다. 모의 대조군(mock)으로 처리된 세포는 대조군으로 사용하였다. 미토콘드리아 멤브레인 포텐셜(potential)을 측정하기 위하여, 세포는 FACS 완충용액 P(PBS, 5 mM EDTA, 0.5% (w/v) BSA, 1 μg/ml 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI, Sigma), 10 nM tetramethylrhodamine ethylester (TMRE, Sigma))에 재용해하였고 분석 전에 37℃에서 30분 동안 배양하였다. 미토콘드리아 멤브레인 포텐셜을 소멸하기 위하여 50 μM의 carbonyl cyanide 3-chlorophenylhydrazone (CCCP, Sigma)를 대조군으로써 처리하였다. 미토콘드리아 ROS 측정을 위하여, 세포는 FACS 완충용액 RR (PBS, 5 mM EDTA, 0.5% BSA), 1 μg/ml DAPI 및 5 μM MitoSOX (Invitrogen)에 재용해하였고, 37℃에서 10분동안 배양한 후, PBS로 세척하였고, FACS 완충용액 R2(PBS, 5 mM EDTA, 0.5% (w/v) BSA)에 재용해하였다. 유동 세포 분석은 FlowJo 소프트웨어(Tree Star Inc.)를 사용하는 CyAnADP(Dako)로 수행하였다.
세포성 세포사멸( apoptosis )의 측정
세포는 PBS(phosphate-buffered saline)에 있는 4% EM-등급 파라포름알데히드(Pierce, 28908)을 사용하여 실온에서 30분 동안 고정하였다. 그런 다음, 세포를 실온에서 15분 동안 PBS에 있는 0.15% Triton X-100으로 투과성화(permeabilized)하였고, 실온에서 1시간동안 PBS에 있는 10%(BSA)로 봉쇄하였다. 샘플은 봉쇄 완충용액에 희석된 마우스 항-사이토크롬(cytochrome) c 항체(BD Biosciences, 556432, 1:1000)으로 4℃에서 하루 동안 배양하였다. 세포는 세 번 세척하였고, 15분 동안 봉쇄 완충용액처리 한 후, 실온에서 1시간 동안 Alexa Fluor 546-결합된 염소 항-마우스 IgG 항체(Invitrogen)으로 배양하였다. 세포사멸의 측정으로써 사이토크롬 c 분비는 블라인드된 관찰자(blinded observer)에 의한 형광 현미경으로 분석하였다. 모의 대조군(mock) 처리된 세포는 대조군으로서 제공하였다.
칼슘 유동( flux ) 측정
세포는 96-웰 Corning® CellBIND® 배양접시에 분주하였고 습한 배양기(37℃; 5% CO2)에서 부착되도록 하였다. 다음 날 세포를 Calcium 5 Assay kit(Molecular Devices, CA, 미국)dmf 사용하여 하기의 방법으로 로딩하였다: 용해된 세포에 대해서, 로딩 완충용액은HBSS/20mM HEPES(pH 7.4)의 두 배의 용액으로 준비하였고 100 ㎕ 배양 배지를 포함하도록 웰에 100 ㎕/웰로 첨가하였다. 부착된 세포에 대해서는 로딩 완충용액을 HBSS/20mM HEPES(pH 7.4)의 일 배의 용액으로 준비하였고, 배양 배지의 흡입 이후에 직접적으로 웰에 100 ㎕/웰로 첨가하였다. 표시된 시점에서, 프로베네시드(probenecid)를 최종 웰 안의 농도가 2.5 mM이 되도록 로딩 완충용액에 첨가하였다. 리간드의 희석을 위하여 HBSS/20mM HEPES(pH 7.4)를 사용하였다. 칼슘 분석은 FlexStation® Instrument (Molecular Devices, CA, 미국)을 사용하여 제조사의 지시를 따라 수행하였다. 데이터 분석은 SoftMax®Pro 소프트웨어를 사용하여 수행하였다.
인간 자궁의( uterine ) 민무늬 근육 세포( hUtSMC ) 격자모양 수축 분석
멸균된 소 콜라겐(3.1 mg/ml; #5005-B Nutacon)의 250 ㎕는 pH7.4에 도달하도록 10x PBS의 30 ㎕ 및 22.5 ㎕ 0.1 N NaOH를 혼합하였다. 200 ㎕의 SMC 배지 2에 있는 25000 hUtSMCs는 콜라겐을 중화하기위해 첨가하였고, 부드럽게 혼합하였으며, 24 웰 조직 배양 배양접시에 이동한 다음, 37℃, 5% CO2에서 45분 동안 중합하였다. 중합반응(polymerization) 이후, SMC 성장 배지 2의 500 ㎕를 첨가하였다. 인공적인 전사 인자의 처리를 위하여, 1 μM ETRA+74VrepSNPS 또는 대조군으로써 적당한 양의 완충용액을 중합반응 바로 후에 첨가하였고 24시간 및 48시간 후에 다시 첨가하였다. 중합반응 72시간 후에, 격자모양은 부드러운 흔들림(shaking) 또는 스파출라 및 ET-1의 100 nM 또는 완충용액 대조군을 첨가하는 것에 의해 혈관 벽으로부터 떼어 내었다. 격자모양은 스캔하였고 격자 영역은 ImageJ 소프트웨어를 사용하는 이미지 분석에 의해 결정하였다.
인간 관상동맥( coronary ) 수축 분석
인간 관상동맥은 해부하여 약 2 mm 길이의 고리 분절로 절단한 후, 96 웰 배양 접시의 웰에 개별적으로 넣었다. 혈관은 penicillin(1000 IU/ml); streptomycin(100 μg/ml), amphotericin(0.25 μg/ml) 및 1 μM ETRA+74VrepS 또는 전파체(vehicle) 대조군이 첨가된 250 ㎕의 RPMI 배지에서 배양하였다. 혈관은 5% CO2의 습한 대기에서 37℃의 배양기에서 삼일 동안 배양하였다. 배지는 24시간 마다 교체하였다. 배지 교체 한 시간 전에, 3 nM endothelin을 혈관에 첨가하였다. 배양 후, 혈관은 PSS(119.0 mM NaCl, 4.7 mM KCl, 1.2 mM MgS04, 24.9 mM NaHCO3, 1.2 mM KH2PO4, 2.5 mM CaCl2 및 11.1 mM glucose)를 포함하는 근운동 기록기 수조(myograph baths; DMT)에 올렸고, 95% O2 및 5% CO2로 탄산화(aerated) 하였으며, 37℃에서 유지하였다. 조직은 포타슘(pottasium) PSS(KPSS; 62.5 mM)에 세번 노출하였고, PSS로 씻어내고 기초점(baseline)으로 돌아가도록 하였다. 그 후, 조직은 U46619(100 nM)에 노출하였고, bradykinin(10 μM)로 배양하였다. 그런 다음, 조직을 씻어내고, 기초점으로 돌아가도록 한 뒤, 누적되는 농도 반응 커브(0, 1, 3, 10, 30, 100, 300 nM endothelin-1)에서 endothelin-1에 노출하였다.
인간화된( humanized ) NSG 마우스에서 과민성( anaphylaxis ) 측정
최소 25%의 인간 CD45+ 세포의 접종(engraftment) 수치를 갖는 인간화된 NSG 마우스(2 마리/그룹-Jackson Laboratories)는 IgeR-147ArepS (30 mg/kg i.v.) 또는 전파체 대조군을 과민성의 유도 96 및 48시간 전에 처리하였다. 마우스는 항-DNP IgE(3 ㎍ i.v.)를 사용하여 민감화(sensitized) 하였고 DNP-BSA(500 ㎍ i.v.) 또는 대조군으로써 BSA(500 ㎍ i.v.)를 처리하여 과민성을 유발하였다. 과민성 유발의 적용 바로 직후에, 30분 동안 5분마다 그리고 다음 90분 동안 15분 마다 그리고 그 후 두 시간 동안 30분 마다 직장의(rectal) 온도를 측정하는 것으로 평가하였다. 30 ℃이하로 체온이 떨어지는 경우엔, 동물을 안락사하였다.
<110> Aliophtha AG <120> Artificial transcription factors engineered to overcome endosomal entrapment <130> 2015FPI-09-015 <150> EP13162197.1 <151> 2013-04-03 <150> PCT/EP 2014/056589 <151> 2014-04-02 <160> 319 <170> PatentIn version 3.5 <210> 1 <211> 98 <212> PRT <213> Homo sapiens <400> 1 Met Asp Ala Lys Ser Leu Thr Ala Trp Ser Arg Thr Leu Val Thr Phe 1 5 10 15 Lys Asp Val Phe Val Asp Phe Thr Arg Glu Glu Trp Lys Leu Leu Asp 20 25 30 Thr Ala Gln Gln Ile Val Tyr Arg Asn Val Met Leu Glu Asn Tyr Lys 35 40 45 Asn Leu Val Ser Leu Gly Tyr Gln Leu Thr Lys Pro Asp Val Ile Leu 50 55 60 Arg Leu Glu Lys Gly Glu Glu Pro Trp Leu Val Glu Arg Glu Ile His 65 70 75 80 Gln Glu Thr His Pro Asp Ser Glu Thr Ala Phe Glu Ile Lys Ser Ser 85 90 95 Val Ser <210> 2 <211> 45 <212> PRT <213> Homo sapiens <400> 2 Arg Thr Leu Val Thr Phe Lys Asp Val Phe Val Asp Phe Thr Arg Glu 1 5 10 15 Glu Trp Lys Leu Leu Asp Thr Ala Gln Gln Ile Val Tyr Arg Asn Val 20 25 30 Met Leu Glu Asn Tyr Lys Asn Leu Val Ser Leu Gly Tyr 35 40 45 <210> 3 <211> 36 <212> PRT <213> Homo sapiens <400> 3 Met Ala Ala Ala Val Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala 1 5 10 15 Asp Tyr Leu Glu Arg Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser 20 25 30 Met Leu Pro Tyr 35 <210> 4 <211> 58 <212> PRT <213> Homo sapiens <400> 4 Gly Ala Ser Gln Cys Met Pro Leu Lys Leu Arg Phe Lys Arg Arg Trp 1 5 10 15 Ser Glu Asp Cys Arg Leu Glu Gly Gly Gly Gly Pro Ala Gly Gly Phe 20 25 30 Glu Asp Glu Gly Glu Asp Lys Lys Val Arg Gly Glu Gly Pro Gly Glu 35 40 45 Ala Gly Gly Pro Leu Thr Pro Arg Arg Val 50 55 <210> 5 <211> 13 <212> PRT <213> herpes simplex virus 7 <400> 5 Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Gly Ser 1 5 10 <210> 6 <211> 55 <212> PRT <213> herpes simplex virus 7 <400> 6 Gly Arg Ala Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Gly Ser 1 5 10 15 Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu 20 25 30 Asp Asp Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe 35 40 45 Asp Leu Asp Met Leu Ile Asn 50 55 <210> 7 <211> 102 <212> PRT <213> Homo sapiens <400> 7 Lys Gly Phe Gly Ala Phe Glu Arg Ser Ile Leu Thr Gln Ile Asp His 1 5 10 15 Ile Leu Met Asp Lys Glu Arg Leu Leu Arg Arg Thr Gln Thr Lys Arg 20 25 30 Ser Val Tyr Arg Val Leu Gly Lys Pro Glu Pro Ala Ala Gln Pro Val 35 40 45 Pro Glu Ser Leu Pro Gly Glu Pro Glu Ile Leu Pro Gln Ala Pro Ala 50 55 60 Asn Ala His Leu Lys Asp Leu Asp Glu Glu Ile Phe Asp Asp Asp Asp 65 70 75 80 Phe Tyr His Gln Leu Leu Arg Glu Leu Ile Glu Arg Lys Thr Ser Ser 85 90 95 Leu Asp Pro Asn Asp Gln 100 <210> 8 <211> 31 <212> PRT <213> Homo sapiens <400> 8 Pro Gly Leu Pro Asn Gly Leu Leu Ser Gly Asp Glu Asp Phe Ser Ser 1 5 10 15 Ile Ala Asp Met Asp Phe Ser Ala Leu Leu Ser Gln Ile Ser Ser 20 25 30 <210> 9 <211> 48 <212> PRT <213> Homo sapiens <400> 9 Pro Tyr Thr Pro Asn Leu Pro His His Gln Asn Gly His Leu Gln His 1 5 10 15 His Pro Pro Met Pro Pro His Pro Gly His Tyr Trp Pro Val His Asn 20 25 30 Glu Leu Ala Phe Gln Pro Pro Ile Ser Asn His Pro Ala Pro Glu Tyr 35 40 45 <210> 10 <211> 100 <212> PRT <213> Homo sapiens <400> 10 Pro Pro His Leu Asn Pro Gln Asp Pro Leu Lys Asp Leu Val Ser Leu 1 5 10 15 Ala Cys Asp Pro Ala Ser Gln Gln Pro Gly Pro Leu Asn Gly Ser Gly 20 25 30 Gln Leu Lys Met Pro Ser His Cys Leu Ser Ala Gln Met Leu Ala Pro 35 40 45 Pro Pro Pro Gly Leu Pro Arg Leu Ala Leu Pro Pro Ala Thr Lys Pro 50 55 60 Ala Thr Thr Ser Glu Gly Gly Ala Thr Ser Pro Thr Ser Pro Ser Tyr 65 70 75 80 Ser Pro Pro Asp Thr Ser Pro Ala Asn Arg Ser Phe Val Gly Leu Gly 85 90 95 Pro Arg Asp Pro 100 <210> 11 <211> 68 <212> PRT <213> Homo sapiens <400> 11 Ala Asp Phe Gln Pro Pro Tyr Phe Pro Pro Pro Tyr Gln Pro Ile Tyr 1 5 10 15 Pro Gln Ser Gln Asp Pro Tyr Ser His Val Asn Asp Pro Tyr Ser Leu 20 25 30 Asn Pro Leu His Ala Gln Pro Gln Pro Gln His Pro Gly Trp Pro Gly 35 40 45 Gln Arg Gln Ser Gln Glu Ser Gly Leu Leu His Thr His Arg Gly Leu 50 55 60 Pro His Gln Leu 65 <210> 12 <211> 112 <212> PRT <213> Homo sapiens <400> 12 Asn Arg Thr Val Ser Gly Gly Gln Tyr Val Val Ala Ala Ala Pro Asn 1 5 10 15 Leu Gln Asn Gln Gln Val Leu Thr Gly Leu Pro Gly Val Met Pro Asn 20 25 30 Ile Gln Tyr Gln Val Ile Pro Gln Phe Gln Thr Val Asp Gly Gln Gln 35 40 45 Leu Gln Phe Ala Ala Thr Gly Ala Gln Val Gln Gln Asp Gly Ser Gly 50 55 60 Gln Ile Gln Ile Ile Pro Gly Ala Asn Gln Gln Ile Ile Thr Asn Arg 65 70 75 80 Gly Ser Gly Gly Asn Ile Ile Ala Ala Met Pro Asn Leu Leu Gln Gln 85 90 95 Ala Val Pro Leu Gln Gly Leu Ala Asn Asn Val Leu Ser Gly Gln Thr 100 105 110 <210> 13 <211> 143 <212> PRT <213> Homo sapiens <400> 13 Gln Gly Gln Thr Pro Gln Arg Val Ser Gly Leu Gln Gly Ser Asp Ala 1 5 10 15 Leu Asn Ile Gln Gln Asn Gln Thr Ser Gly Gly Ser Leu Gln Ala Gly 20 25 30 Gln Gln Lys Glu Gly Glu Gln Asn Gln Gln Thr Gln Gln Gln Gln Ile 35 40 45 Leu Ile Gln Pro Gln Leu Val Gln Gly Gly Gln Ala Leu Gln Ala Leu 50 55 60 Gln Ala Ala Pro Leu Ser Gly Gln Thr Phe Thr Thr Gln Ala Ile Ser 65 70 75 80 Gln Glu Thr Leu Gln Asn Leu Gln Leu Gln Ala Val Pro Asn Ser Gly 85 90 95 Pro Ile Ile Ile Arg Thr Pro Thr Val Gly Pro Asn Gly Gln Val Ser 100 105 110 Trp Gln Thr Leu Gln Leu Gln Asn Leu Gln Val Gln Asn Pro Gln Ala 115 120 125 Gln Thr Ile Thr Leu Ala Pro Met Gln Gly Val Ser Leu Gly Gln 130 135 140 <210> 14 <211> 95 <212> PRT <213> Homo sapiens <400> 14 Asp Leu Gln Gln Leu Gln Gln Leu Gln Gln Gln Asn Leu Asn Leu Gln 1 5 10 15 Gln Phe Val Leu Val His Pro Thr Thr Asn Leu Gln Pro Ala Gln Phe 20 25 30 Ile Ile Ser Gln Thr Pro Gln Gly Gln Gln Gly Leu Leu Gln Ala Gln 35 40 45 Asn Leu Leu Thr Gln Leu Pro Gln Gln Ser Gln Ala Asn Leu Leu Gln 50 55 60 Ser Gln Pro Ser Ile Thr Leu Thr Ser Gln Pro Ala Thr Pro Thr Arg 65 70 75 80 Thr Ile Ala Ala Thr Pro Ile Gln Thr Leu Pro Gln Ser Gln Ser 85 90 95 <210> 15 <211> 63 <212> PRT <213> Homo sapiens <400> 15 Gln Leu Ala Gly Asp Ile Gln Gln Leu Leu Gln Leu Gln Gln Leu Val 1 5 10 15 Leu Val Pro Gly His His Leu Gln Pro Pro Ala Gln Phe Leu Leu Pro 20 25 30 Gln Ala Gln Gln Ser Gln Pro Gly Leu Leu Pro Thr Pro Asn Leu Phe 35 40 45 Gln Leu Pro Gln Gln Thr Gln Gly Ala Leu Leu Thr Ser Gln Pro 50 55 60 <210> 16 <211> 90 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 16 Asn Leu Phe Gln Leu Pro Gln Gln Thr Gln Gly Ala Leu Leu Thr Ser 1 5 10 15 Gln Pro Asn Leu Phe Gln Leu Pro Gln Gln Thr Gln Gly Ala Leu Leu 20 25 30 Thr Ser Gln Pro Asn Leu Phe Gln Leu Pro Gln Gln Thr Gln Gly Ala 35 40 45 Leu Leu Thr Ser Gln Pro Asn Leu Phe Gln Leu Pro Gln Gln Thr Gln 50 55 60 Gly Ala Leu Leu Thr Ser Gln Pro Asn Leu Phe Gln Leu Pro Gln Gln 65 70 75 80 Thr Gln Gly Ala Leu Leu Thr Ser Gln Pro 85 90 <210> 17 <211> 91 <212> PRT <213> Homo sapiens <400> 17 Pro Pro Ser Thr Gly Asn Ser Ala Ser Leu Ser Leu Pro Leu Val Leu 1 5 10 15 Gln Pro Gly Leu Ser Glu Pro Pro Gln Pro Leu Leu Pro Ala Ser Ala 20 25 30 Pro Ser Ala Pro Pro Pro Ala Pro Ser Leu Gly Pro Gly Ser Gln Gln 35 40 45 Ala Ala Phe Gly Asn Pro Pro Ala Leu Leu Gln Pro Pro Glu Val Pro 50 55 60 Val Pro His Ser Thr Gln Phe Ala Ala Asn His Gln Glu Phe Leu Pro 65 70 75 80 His Pro Gln Ala Pro Gln Pro Ile Val Pro Gly 85 90 <210> 18 <211> 111 <212> PRT <213> Homo sapiens <400> 18 Met Ala Thr Arg Val Leu Ser Met Ser Ala Arg Leu Gly Pro Val Pro 1 5 10 15 Gln Pro Pro Ala Pro Gln Asp Glu Pro Val Phe Ala Gln Leu Lys Pro 20 25 30 Val Leu Gly Ala Ala Asn Pro Ala Arg Asp Ala Ala Leu Phe Pro Gly 35 40 45 Glu Glu Leu Lys His Ala His His Arg Pro Gln Ala Gln Pro Ala Pro 50 55 60 Ala Gln Ala Pro Gln Pro Ala Gln Pro Pro Ala Thr Gly Pro Arg Leu 65 70 75 80 Pro Pro Glu Asp Leu Val Gln Thr Arg Cys Glu Met Glu Lys Tyr Leu 85 90 95 Thr Pro Gln Leu Pro Pro Val Pro Ile Ile Pro Glu His Lys Lys 100 105 110 <210> 19 <211> 88 <212> PRT <213> Homo sapiens <400> 19 Met Ala Leu Ser Glu Pro Ile Leu Pro Ser Phe Ser Thr Phe Ala Ser 1 5 10 15 Pro Cys Arg Glu Arg Gly Leu Gln Glu Arg Trp Pro Arg Ala Glu Pro 20 25 30 Glu Ser Gly Gly Thr Asp Asp Asp Leu Asn Ser Val Leu Asp Phe Ile 35 40 45 Leu Ser Met Gly Leu Asp Gly Leu Gly Ala Glu Ala Ala Pro Glu Pro 50 55 60 Pro Pro Pro Pro Pro Pro Pro Ala Phe Tyr Tyr Pro Glu Pro Gly Ala 65 70 75 80 Pro Pro Pro Tyr Ser Ala Pro Ala 85 <210> 20 <211> 11 <212> PRT <213> Human immunodeficiency virus <400> 20 Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg 1 5 10 <210> 21 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 21 Pro Val Arg Arg Pro Arg Arg Arg Arg Arg Arg Lys 1 5 10 <210> 22 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 22 Thr His Arg Leu Pro Arg Arg Arg Arg Arg Arg Lys 1 5 10 <210> 23 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 23 Arg Arg Arg Arg Arg Arg Arg Arg Arg 1 5 <210> 24 <211> 16 <212> PRT <213> Drosophila melanogaster <400> 24 Arg Gln Ile Leu Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys 1 5 10 15 <210> 25 <211> 20 <212> PRT <213> Influenza A virus <400> 25 Gly Asp Ile Met Gly Glu Trp Gly Asn Glu Ile Phe Gly Ala Ile Ala 1 5 10 15 Gly Phe Leu Gly 20 <210> 26 <211> 30 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 26 Trp Glu Ala Lys Leu Ala Lys Ala Leu Ala Lys Ala Leu Ala Lys His 1 5 10 15 Leu Ala Lys Ala Leu Ala Lys Ala Leu Lys Ala Cys Glu Ala 20 25 30 <210> 27 <211> 30 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 27 Trp Glu Ala Ala Leu Ala Glu Ala Leu Ala Glu Ala Leu Ala Glu His 1 5 10 15 Leu Ala Glu Ala Leu Ala Glu Ala Leu Glu Ala Leu Ala Ala 20 25 30 <210> 28 <211> 10 <212> PRT <213> Homo sapiens <400> 28 Gln Pro Met Lys Arg Leu Thr Leu Gly Asn 1 5 10 <210> 29 <211> 6950 <212> DNA <213> Homo sapiens <400> 29 gtgtctatga atttaactat tctaggtacc tcatctaagt gggataataa aatatctatc 60 tttcctttta tgtctggctt atttcactta acataatatc ttaaacgttc atccatgtgg 120 tagcatatat cattcttttt taaagctgaa taatgttctg tgttatgtac atgtatttat 180 atacatatac atacatgtat ataccacatt ttgtttatcc attcttccac tgatggatat 240 ttggattgtt tccatctttt ggctagtttt caccttttgg cttttctgaa taatgctgct 300 atgaatatgg gtgtacaaat atctgtttga gactctgctt tcaattattt aggtaagtac 360 caaaaagtag aattgctgga tcatagggta attttatgtt taatttttgg agggctgcca 420 tgctgttttc cacaactgct acactatatt ttacattcag actggcaatg cacaagggtt 480 ccaatttctc aacattcttg ccaacacttg ttctttgctg tttttgcttt tgttttacta 540 taatggctat cctaataggt gtgaaggaag aatttttagt aactagtcct acaccacagt 600 gagatcagct gtctcaatag gtgggtcatg atgaatgtgt tctagcaaag actggacaga 660 ttgacatatt cagatatgca ggtgatgcac tgtccaagtg tgtctggcca cagagtgaat 720 aagggctgaa atccagcaca tgtttcacgg gccaagatgt gaactgcctc ttttgggagg 780 aagcagtaag tttttctttc ccgaaaatat tgtcagcttg ccaagccaca tgcccaaagg 840 gtcacctttt tttaatataa acaatggcac ttataaaagc tattagttat tctggttggc 900 tgattctccc tcctagagaa gctgtaagat tagtgaacag ggtaatatct agtctaaccc 960 tactagatga ctattaaggc ctctttcaat ggtggttttc tgtagatctc tttgatggtt 1020 ttacaaaatg gtccctaaat tctttgacac tcctcacact aagggttggg ctctatatac 1080 cctcaccttc aatctgggat ttgtgactgc ttgactaata gaatcaagca gaaatgacac 1140 ggtgccagtt tctgggccca gcccttaaga aactggcagc ttccactttc tgtctctggg 1200 gacattcact cttggatccc cgccaccatg ctgtgaggaa gcccaaacca caagtctcca 1260 caagtctttg tggagagacg cacgtggaga aaaactaaca ctcaacacca agcaagtgaa 1320 ctgtcttgga agtggatcct ccagcccctg ctacatggag caaaaacgag ctgtcccaga 1380 caggctctgc ccaaactgca gactgataag cagagtaaat gagtgttgtt attttaagcc 1440 actacgtttt atagtaattt gtttagctgc agcagatagc cggaacagca tgggatataa 1500 catgaccagt gctccaacct cacacttcta ccatgtgctg actctagcag tgcactgaag 1560 gactccaagg caggccttcc ctgaggagac cccagttttt actcacatgt cacaggcagt 1620 ggcctttgtc cctcatctcc tctcccaccc ccaatttagg ataaagtatc tgccgtgata 1680 aagacgttga gacccacttt ctgtaaggtc ggcttcttca ttgtttgaat ttcttgaggt 1740 ttcacggagc cacgcgctgg aaccttccat agtctctcct gaggctcctt ctttgccctg 1800 ggctggaggt ctgtagccgt gggatgctgg ctacaaggga caagatagaa gcaaaccacc 1860 tgatccagta aactgctgtc cacttcggct cctcaacggc ctctaagctt aagagggagc 1920 acgcaagcca agcaaaggcg gcagggaaga cggagaagaa accacccgtg ggccctggct 1980 ctgtgtccag ttgttccgtc acagatcaaa tctgcctgca ctaagaggat gggttcctct 2040 gcaaggcctt tcggaattct gagtcttgtc tgtcaaactc taccctctct cctccacatc 2100 ccccaccttt tctttcagga aggaaatagt taaaaaagac tcctgccctt cagggcctgg 2160 aagggggcgg cagctttgtg ctttttagtg gccgcgtccc aggatagctg gaaggttagg 2220 acgctcttgc ggtcccagag tggagtggaa ggtctggagc tttgggagga gacggggagg 2280 acagactgga ggcgtgttcc tccggagttt tctttttcgt gcgagccctc gcgcgcgcgt 2340 acagtcatcc cgctggtctg acgattgtgg agaggcggtg gagaggcttc atccatccca 2400 cccggtcgtc gccggggatt ggggtcccag cgagacctcc ccgggagaag cagtgcccag 2460 gaggttttct gaagccgggg aagctgtgca gccgaagccg ccgccgcgcc ggagcccggg 2520 acaccggcca ccctccgcgc cacccaccct cgccggctcc ggcttcctct ggcccaggcg 2580 ccgcgcggac ccggcagctg tctgcgcacg ccgagctcca cggtcggtgc aagtctttct 2640 tatcggggac tgggactggg gcgggtgcgg ggatggcgga gacgctgcct gggcccctcg 2700 gtcgggagaa gacgagagct gggaacgttc tggcccgacc gccctgcagc ttgggcgacc 2760 cgtcgcagca ggggctggca cccacttgcc ccagggcgcg cggggaggcg ggcgccttcc 2820 gtgaggggtg cgctgcggac acgtgtagag ttcggggaac ttcacctctc cacgttaggg 2880 tttaggattc ggagttttag gaagaggaag cccaatagtt ttccctgggt gacccctttt 2940 ccccaggcat gcaagaactt tgaggaacgc caagctctgt ggcttgctcc agcgccttct 3000 tgtgaagttg gctccacagc cttttcttac tggcttgctt ttcctccccc acatctgggt 3060 ctgggtatgc caagggtagc caagggcact cggtgtgagg gactgaggtg tttggggaaa 3120 ccccctgtgt agctagtttt ggaaacctgc ctgtggaggt ctgggcgttt tgttctgtgc 3180 tcgcctttaa aggacacttg ttgcttctca cgtgcagaaa acaagggctg cttctagata 3240 atcaccctct gtttacatca tcctaatggc tttcccctga tagagttggg ggtgggaggc 3300 atattaaact caggcgttgt ctctaaggag agttgctcat ttcttaacca gagagcaaaa 3360 cctcagaaaa cttgtaaaaa gttcctactt ttacttgttt tttcctccac ctgtagttgt 3420 ctatgtgtta gctaattgag aaacaccttg gcagtcattt catgtaaatt gaatgctcta 3480 aactcatgcc attttgataa ggtctgaatt tccaaattac caattacagg tgaactttga 3540 tcctgagagt ctcatatgtt aaatggttaa agtgtaagcg taaggattca gtcctctttc 3600 ttaataatag tttttgcact ccccaaactc tcagattcca aacaggaaga atgctgaatc 3660 tatagaccat gtccttcagg tctgaacctg agatgcttca ctagcgctat gactgattat 3720 gagtgatgat tcaaagcaca gcctgactca gattcctgga aatgagctac agacccacct 3780 tggaagaacc tgcagttgag gggcttcttt catttggttt tgtacttttc agccaatgat 3840 aatatgacat ccacaggcct ttgccaagta tcccttagtt ttgcagctta acatgtgtgg 3900 agagctgata gagaagtcat cagaaatgat ttctgtagtg gtgtcattgt tggaggagga 3960 aggaaggggg ttttaatgat agctggctct catgccttaa gaacccacag cgttggcctt 4020 acctcctggc ataatcagct aaccaagcag accagcatgc taacgttcaa agcaccacag 4080 gacctctgat gagtagagca gtacccaccg tagccaggtc agttcacagg tcagttccca 4140 gccgactgta accggcagag agccattcca tttctgcaaa ggccttctct ctctcatttt 4200 taagaaagct gttattgaag gttccctttc atttgggaag ctggaagacg ttagtcacga 4260 aacagcacaa gatatgaaag tatttcttct cccccctgta tctgtgatcc aaaaaggagg 4320 atgacaagaa gcttttctct tggagtcctg gtgttccctt tggaatggaa atggtgtcat 4380 ttcataggtc tatcaatttt tggccagata ctcactccag attataagaa gcaggaaaaa 4440 actgcaaact gtttataatt aagtctagtc agagctgaca aatacatggc ctgcctctag 4500 ccttgaaaaa ttgatatttt tcccatttaa tcagagtgag tcaagtccta taagcaaaat 4560 tatgtgtcct gccatttctt ggctttgaaa ccttgaccta aatacttctt caagactctg 4620 gtttccttat aagtaaaatg gagatattgc tcctgcctac ctagagtcgt aaagctcaag 4680 gcagataaca gatacatata taataagtta ctatatgtaa atactattat tatttcagag 4740 ttcaggggga aatctctggg gaaggcaaaa gtatccaata ctcgcacttt atatataccc 4800 tatactttct atgcaacttg aataaatctt attttatcca cgtattggcc aaacctaagc 4860 tttactgatt tcccaagata attgtcaaaa ttcctaaaag tggttaacat caaccttgaa 4920 tacactcaga aaaaggattc aattttattt tttacttttt atttatttaa tttttttttt 4980 tttgagacag ggtctcactc tgctgctcag gatggagtgc agtgactcga tcatagctcc 5040 ctgcagcctt aacctcctgg actcaagtga ttctcccatc tcagcctccc aagtagctga 5100 gactacaggc acacgccacc atgcctgtct aatctttttt atgttttgta aagacagggt 5160 ctcactaagt tgcccaggct agtttcaaac tcctgggctc aagtgatcct cctgctttgg 5220 cctcccaaag tgctgagatt atagacatga gccaccacac ccaaccagga ctcaattttt 5280 ttaagattaa attatgacct gggtatatac atcacagaca cgtacacaca ccaccgcata 5340 aatcagatta tgtcttcatt tgaagattca taaaagccta cagaaaagga aatatataaa 5400 atattgaaat aggatgagct atttttaatt atctttgatt attccttatt aaggtctcct 5460 agacttcctg gacaggaagg accacttgct ctctgcaagt gacttaaaaa taaataaata 5520 aataaataaa ccacaccaga tggtctttga aaatgtctaa ccaccctcct gagtctattg 5580 cttcatctaa actctggaga cttctttaaa atattttaca tacaaataaa gcacaagaat 5640 gagagacagg atggtttagt ggttaacagc tccggctcag agttggactg acctgcctta 5700 gaatcgcagt gttgccaccc atcacctgtg gccttgacaa gctgcttcac cctcctgggc 5760 ctctgtttcc ctatcttcaa aattgaaccg tggatctacc ccacaggacc attgtatgga 5820 ttacagggca tcatgcacat atagtactga gtacagtgac tggcataaaa taaatgtagc 5880 tatataggat ggttaaaaga tagcatgggg acaggtgtcc cttggaaacc aaaatactat 5940 gactagcctg gaaaagttca ttactcccat ttcattcatc ggcaaatacc gtattgtgat 6000 gataatttct gagaaatgaa aaagcaaaaa aactcctgta aaaaatttag attttacaca 6060 ttaatcatca aggttttcaa aacaaatgtt tttatcaatt atttcattct taattgaaac 6120 taaaattgtt agatgtgtta atggtgttaa ccagagttct cattaacatt tcataacact 6180 ttagatggct acctgtgctg cacttcatcc ctatgttcat tatttatcat atgcaagaca 6240 gcacacattt tagaagattc aatttttaca ttcgataatt ttattttatg cctcaatacc 6300 ctgtaccctt tactcagcat ataatgcctt ttctctttca ttaaaaaata tgtttgtatc 6360 tcaactcttg aagatttttg taattcaggt tcttatcagc ctgaatgtag agaaagaagt 6420 aactactact taaaggaaaa actgacatag cctcatccat attatgatgt agatataagt 6480 atagctatgt atagagatga gtgagagaga caaagctaga gagataggga gatggagata 6540 gagctagaga tggaaataga gacagagata gatagctata gagacggaaa tggagacaga 6600 gacagagacg gagatgacag agatgatgga gatgatggag atggagatgg agactgacat 6660 agaggagata gagcttgccc taatagagct tcagtttttt tctggttttg ctctgtcata 6720 gggtaacctg atatacatat atcttatcta atcaccaaat atatcctgca ttttaattga 6780 atcaataaat aatcattgac tatgatcttt ttggcaactg ggttttggaa caaaaattat 6840 ttttcctttt gtttcaggtg aaaaaaaagt gaaggtgtaa aagcagcaca agtgcaataa 6900 gagatatttc ctcaaatttg cctcaagatg gaaacccttt gcctcagggc 6950 <210> 30 <211> 1180 <212> DNA <213> Homo sapiens <400> 30 tgtccccgga cgaggactgc ccccctccct cgggcaacta ctactgatgc tgtccaggca 60 tcgcccaagg ggaaaggttg cagcggggtc ggaaggcgcg ggaggagtct ggcggtgatt 120 gatgggaagg gatgaatgaa taaaagtact tgtctgatgg cagcagagac cccgagcaaa 180 cggtggaggc tacactgtct ggcattctcg cagcgtttcg tcagagccgg acccgcctgc 240 agctcaaggg aggcgtgctc ctctcccaga gcaggctgga acccagctgg gttccgcctc 300 ccgggaaggt ggtctccatt cgtcgctctg catctggttt gtcagatccg agaggtaaac 360 attcgggctt ggtgttgaat taaaatcatt gattgaacct tattctgggg cttcggtttg 420 gcttactagt ttgggatttt aaaaaaataa aaattaagcc tatagagagg gcaaattaaa 480 attaggttgg gtaaaggaag gagcgcgagt gtttgaagcc gtttggaggg aacagcggtt 540 tccaagttcc tgctgacttg agaagtctct gcgggtttcc gaatctccgg cgcactcctg 600 ggcgcgctgc gggagctgta gctcagccag ccagggagta gcggctttca tccgccggga 660 ggagtctttc gagttcaatc gcggggtata gaggttcccc tgcggggcaa aatgcagagc 720 ttgacacaag cccttggcct ctaggtgcct taattccgcg gttcccacgc acgcttaact 780 aagacgtgtc tgtattcctc ccgttacgtg aaagagttcg gagctttgcc tgggaccccc 840 atcattccct ccctggcaca ccccttccag aacgccccgc cccactgcat attatttacc 900 cctcctggcc acgcggggga agaaaaacag ctgagagggc atcaggaagg agtttcgacc 960 cgcgctggcg agtcatgagc gccaagtttc ccactggcgc gcaaacttga gttacttttg 1020 agcgtggata ctggcgaaga ggctgcgggc ggtattagcg tttgcagcga cttggctcgg 1080 gcagctgacc caagtgtcct gtcttccttc ctctgcttgt ctctaggctc tgaaactgcg 1140 gagcggccac cggacgcctt ctggagcagg tagcagcatg 1180 <210> 31 <211> 644 <212> DNA <213> Homo sapiens <400> 31 ccttgagttc agactggaag cctctagaat tgtgagaaaa tgaatgtctg ttgtttaagc 60 cacccagtct gtggtatttc cttatggcag ccccagcaaa ctaatacaaa tagtgtttcc 120 acagctgaaa caaaattgga aaatcaccgt catcctagag agttacaagg gctattttaa 180 tagaacctga ttgttttcct aaattcacca agcccaggca gaggtcagat gactaattgg 240 gataaaagcc aactagcttc ctcttgctgt ttctttagcc actggtctgc aggcgttttc 300 ttcttctaac ttcctctcct gtgacaaaag agataactat tagagaaaca aaagtccaga 360 atgctaaggt tgccgctttc acttcctctc accctttagc ccagaactgc tttgaataca 420 ccaattgctg tggggcggct cgaggaagag aagacaccag tgcctcagaa actgctcggt 480 cagacggtga tagcgagcca cgcattcaca gggccactgc tgctcacaga agcagtgagg 540 atgatgccag gatgatgtct gcctcgcgcc tggctgggac tctgatccca gccatggcct 600 tcctctcctg cgtgagacca gaaagctggg agccctgcgt ggag 644 <210> 32 <211> 220 <212> DNA <213> Homo sapiens <400> 32 taagtgggta aatattaaat tgcccagttg ggcaccatcc tgaatattat ctctaaagaa 60 agaagcaaaa ccaggcacag ctgatgggtt aaccagatat gatacagaaa acatttcctt 120 ctgctttttg gttttaagcc tatatttgaa gccttagatc tctccagcac agtaagcacc 180 aggagtccat gaagaagatg gctcctgcca tggaatcccc 220 <210> 33 <211> 1000 <212> DNA <213> Homo sapiens <400> 33 cgactccccc cgggcccaaa gtacgtatgc gccgaccccc gctatcccgt cccttccctg 60 aagcctcccc agagggcgtg tcaggccgcc cggccccgag cgcggccgag acgctgcggc 120 accgtttccg tgcaaccccg tagccccttt cgaagtgaca cacttcacgc aactcggccc 180 ggcggcggcg gcgcgggcca ctcacgcagc tcagccgcgg gaggcgcccc ggctcttgtg 240 gcccgcccgc tgtcacccgc aggggcactg gcggcgcttg ccgccaaggg gcagagcgag 300 ctcccgagtg ggtctggagc cgcggagctg ggcgggggcg ggaaggaggt agcgagaaaa 360 gaaactggag aaactcggtg gccctcttaa cgccgcccca gagagaccag gtcggccccc 420 gccgctgccg ccgccaccct ttttcctggg gagttggggg cggggggcga agcgcggcgc 480 accgggcggg gcggccacgc caggggacgc gggcgtgcag gcgccgtcgg ggccggggtg 540 gcggggcccg cgcggagggc gtgggggcag ggaccgcggg cgcccctgca gttgccaagc 600 gtcaccaaca ggttgcatcg ttccccgcgg ccgccgcgcg gcccctcggg cggggagcgg 660 ccgggggtgg agtgggagcg cgtgtgtgcg agtgtgtgcg cgccgtggcg ccgcctccac 720 ccgctccccg ctcggtcccg ctcgctcgcc caggccgggc tgccctttcg cgtgtccgcg 780 ctctcttccc tccgccgccg cctcctccat tttgcgagct cgtgtctgtg acgggagccc 840 gagtcaccgc ctgcccgtcg gggacggatt ctgtgggtgg aaggagacgc cgcagccgga 900 gcggccgaag cagctgggac cgggacgggg cacgcgcgcc cggaacctcg acccgcggag 960 cccggcgcgg ggcggagggc tggcttgtca gctgggcaat 1000 <210> 34 <211> 1000 <212> DNA <213> Homo sapiens <400> 34 agcaaacgtt tacagagctc tggacaaaat tgagcgccta tgtgtacatg gcaagtgttt 60 ttagtgtttg tgtgtttacc tgcttgtctg ggtgattttg cctttgagag tctggatgag 120 aaatgcatgg ttaaaggcaa ttccagacag gaagaaaggc agagaagagg gtagaaatga 180 cctctgattc ttggggctga gggttcctag agcaaatggc acaatgccac gaggcccgat 240 ctatccctat gacggaatct aaggtttcag caagtatctg ctggcttggt catggcttgc 300 tcctcagttt gtaggagact ctcccactct cccatctgcg cgctcttatc agtcctgaaa 360 agaacccctg gcagccagga gcaggtattc ctatcgtcct tttcctccct ccctcgcctc 420 caccctgttg gttttttaga ttgggctttg gaaccaaatt tggtgagtgc tggcctccag 480 gaaatctgga gccctggcgc ctaaaccttg gtttaggaaa gcaggagcta ttcaggaagc 540 aggggtcctc cagggctaga gctagcctct cctgccctcg cccacgctgc gccagcactt 600 gtttctccaa agccactagg caggcgttag cgcgcggtga ggggagggga gaaaaggaaa 660 ggggagggga gggaaaagga ggtgggaagg caaggaggcc ggcccggtgg gggcgggacc 720 cgactcgcaa actgttgcat ttgctctcca cctcccagcg ccccctccga gatcccgggg 780 agccagcttg ctgggagagc gggacggtcc ggagcaagcc cagaggcaga ggaggcgaca 840 gagggaaaaa gggccgagct agccgctcca gtgctgtaca ggagccgaag ggacgcacca 900 cgccagcccc agcccggctc cagcgacagc caacgcctct tgcagcgcgg cggcttcgaa 960 gccgccgccc ggagctgccc tttcctcttc ggtgaagttt 1000 <210> 35 <211> 1000 <212> DNA <213> Homo sapiens <400> 35 tgcattttaa aaatctgtta gctggaccag accgacaatg taacataatt gccaaagctt 60 tggttcgtga cctgaggtta tgtttggtat gaaaaggtca cattttatat tcagttttct 120 gaagttttgg ttgcataacc aacctgtgga aggcatgaac acccatgtgc gccctaacca 180 aaggtttttc tgaatcatcc ttcacatgag aattcctaat gggaccaagt acagtactgt 240 ggtccaacat aaacacacaa gtcaggctga gagaatctca gaaggttgtg gaagggtcta 300 tctactttgg gagcattttg cagaggaaga aactgaggtc ctggcaggtt gcattctcct 360 gatggcaaaa tgcagctctt cctatatgta taccctgaat ctccgccccc ttcccctcag 420 atgccccctg tcagttcccc cagctgctaa atatagctgt ctgtggctgg ctgcgtatgc 480 aaccgcacac cccattctat ctgccctatc tcggttacag tgtagtcctc cccagggtca 540 tcctatgtac acactacgta tttctagcca acgaggaggg ggaatcaaac agaaagagag 600 acaaacagag atatatcgga gtctggcacg gggcacataa ggcagcacat tagagaaagc 660 cggcccctgg atccgtcttt cgcgtttatt ttaagcccag tcttccctgg gccaccttta 720 gcagatcctc gtgcgccccc gccccctggc cgtgaaactc agcctctatc cagcagcgac 780 gacaagtaaa gtaaagttca gggaagctgc tctttgggat cgctccaaat cgagttgtgc 840 ctggagtgat gtttaagcca atgtcagggc aaggcaacag tccctggccg tcctccagca 900 cctttgtaat gcatatgagc tcgggagacc agtacttaaa gttggaggcc cgggagccca 960 ggagctggcg gagggcgttc gtcctgggac tgcacttgct 1000 <210> 36 <211> 1000 <212> DNA <213> Homo sapiens <400> 36 gaaatttggg aggggagcca tcaaagaagc ctgggagcag cagttccagg gaaaaaggag 60 aatgtgatgg ccagagagcc aaaagaaaaa gtagttgaag gagtgctcag cactaggcat 120 ctgaactgaa tgctgtggca ggctcactgg ccacaaacaa tagggagctg gtggaggcct 180 tgacgaggac catttcaaca aactggtggg cttaaaatcc ggaagaaaca gttgaacaaa 240 tcattttgac gccttttata aaccacacaa gcttattcca aacccgttac tggcctaact 300 gatttaagtc cctttcccat ctgatcctca gagattctaa gggacttagc ctatccatga 360 ctcttcgtcc tgcttctcac ctcccatgat tgccctaacg atgtgaaagt gctttcaaac 420 aaagatgccc aagaaagaag gtaggcaaat gtgcaagcat tagtttgtag tacgctatta 480 ctgtatttca ccttgcactc tctagtttcc ttcgtgctcc ctcaatatcc aactcttaat 540 aaattcatgg ctcccggtga gcattcatca attctcattc cacgccttta gcccttcccg 600 ttcccgccca actctcgctc cctcccctgg ccaaatctct aacctgcaag gctaattccg 660 aattccaaat cggaagcaag agggcggggc cccgtgagag gcgatggatt gctccagtcc 720 gttcccgacg cactgtgcgc atgcgctggt cctccgcgga ccgttcgtgc tgcccgccta 780 gaaagggtga agtggttgtt tccgtgacgg actgagtacg ggtgcctgtc aggctcttgc 840 ggaagtccat gcgccattgg gagggcctcg gccgcggctc tgtgcccttg ctgctgaggg 900 ccacttcctg ggtcattcct ggaccgggag ccgggctggg gctcacacgg gggctcccgc 960 gtggccgtct cggcgcctgc gtgacctccc cgccggcggg 1000 <210> 37 <211> 7 <212> PRT <213> Simian virus 40 <400> 37 Pro Lys Lys Lys Arg Lys Val 1 5 <210> 38 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 38 Gly Gly Ser Gly Gly Ser 1 5 <210> 39 <211> 18 <212> DNA <213> Homo sapiens <400> 39 ggcctggaag ggggcggc 18 <210> 40 <211> 18 <212> DNA <213> Homo sapiens <400> 40 cctgcccttc agggcctg 18 <210> 41 <211> 18 <212> DNA <213> Homo sapiens <400> 41 ggaggagacg gggaggac 18 <210> 42 <211> 18 <212> DNA <213> Homo sapiens <400> 42 ctcgggcaac tactactg 18 <210> 43 <211> 18 <212> DNA <213> Homo sapiens <400> 43 gaggttcccc tgcggggc 18 <210> 44 <211> 18 <212> DNA <213> Homo sapiens <400> 44 gctgtggggc ggctcgag 18 <210> 45 <211> 18 <212> DNA <213> Homo sapiens <400> 45 agcttcctct tgctgttt 18 <210> 46 <211> 18 <212> DNA <213> Homo sapiens <400> 46 caccaagccc aggcagag 18 <210> 47 <211> 18 <212> DNA <213> Homo sapiens <400> 47 gcccagttgg gcaccatc 18 <210> 48 <211> 18 <212> DNA <213> Homo sapiens <400> 48 gtccatgaag aagatggc 18 <210> 49 <211> 18 <212> DNA <213> Homo sapiens <400> 49 agcgtcgaac ggccacag 18 <210> 50 <211> 18 <212> DNA <213> Homo sapiens <400> 50 cgcgcggagg gcgtgggg 18 <210> 51 <211> 18 <212> DNA <213> Homo sapiens <400> 51 cggggagcgg ccgggggt 18 <210> 52 <211> 18 <212> DNA <213> Homo sapiens <400> 52 gcctccaccc gctccccg 18 <210> 53 <211> 18 <212> DNA <213> Homo sapiens <400> 53 ctccagggct agagctag 18 <210> 54 <211> 18 <212> DNA <213> Homo sapiens <400> 54 ggcccggtgg gggcggga 18 <210> 55 <211> 18 <212> DNA <213> Homo sapiens <400> 55 agcgggacgg tccggagc 18 <210> 56 <211> 18 <212> DNA <213> Homo sapiens <400> 56 gcaggagcta ttcaggaa 18 <210> 57 <211> 18 <212> DNA <213> Homo sapiens <400> 57 tccagcagcg acgacaag 18 <210> 58 <211> 18 <212> DNA <213> Homo sapiens <400> 58 gtccctggcc gtcctcca 18 <210> 59 <211> 18 <212> DNA <213> Homo sapiens <400> 59 gttggaggcc cgggagcc 18 <210> 60 <211> 18 <212> DNA <213> Homo sapiens <400> 60 gaaaaagtag ttgaagga 18 <210> 61 <211> 18 <212> DNA <213> Homo sapiens <400> 61 gtagttgaag gagtgctc 18 <210> 62 <211> 18 <212> DNA <213> Homo sapiens <400> 62 gacctccccg ccggcggg 18 <210> 63 <211> 18 <212> DNA <213> Homo sapiens <400> 63 cttgcggaag tccatgcg 18 <210> 64 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 64 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu 35 40 45 Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 65 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 65 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 66 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 66 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 145 150 155 160 Arg Ala His Gln Arg Thr His Thr 165 <210> 67 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 67 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu 35 40 45 Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Asn Ser Thr Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 68 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 68 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser 1 5 10 15 Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu 35 40 45 Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser His Ser Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 69 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 69 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser 1 5 10 15 Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser His Thr Gly His Leu Leu Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 145 150 155 160 Arg Ala His Gln Arg Thr His Thr 165 <210> 70 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 70 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 71 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 71 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 72 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 72 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser His Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 73 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 73 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser His Ser Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 74 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 74 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu 35 40 45 Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 75 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 75 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 76 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 76 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser 1 5 10 15 Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 145 150 155 160 Arg Ala His Gln Arg Thr His Thr 165 <210> 77 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 77 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu 35 40 45 Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 78 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 78 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Lys Lys Ala Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 145 150 155 160 Arg Ala His Gln Arg Thr His Thr 165 <210> 79 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 79 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 80 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 80 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 81 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 81 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 82 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 82 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 83 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 83 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 84 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 84 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 85 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 85 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 86 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 86 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 87 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 87 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 88 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 88 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 89 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 89 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 90 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 90 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 91 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 91 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 92 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 92 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 93 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 93 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala 180 185 190 His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 94 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 94 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 95 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 95 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 96 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 96 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 97 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 97 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 98 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 98 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 99 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 99 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 100 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 100 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 101 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 101 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala 180 185 190 His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 102 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 102 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 103 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 103 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 104 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 104 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 105 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 105 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 106 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 106 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 107 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 107 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 108 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 108 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 109 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 109 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 110 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 110 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 111 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 111 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 112 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 112 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 113 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 113 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 114 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 114 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys 115 120 125 Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 115 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 115 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 116 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 116 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 117 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 117 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp 180 185 190 Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 118 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 118 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Asn Ser Thr Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 119 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 119 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Asn Ser Thr Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 120 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 120 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 His Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 121 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 121 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser His Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp 180 185 190 Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 122 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 122 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Thr 115 120 125 Gly His Leu Leu Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 123 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 123 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser His Thr Gly His Leu Leu Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp 180 185 190 Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 124 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 124 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 125 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 125 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 126 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 126 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg 145 150 155 160 Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 127 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 127 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg 180 185 190 Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 128 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 128 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser His Ser Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 129 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 129 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser His Ser Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn 180 185 190 Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 130 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 130 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 131 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 131 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys 180 185 190 His Leu Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 132 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 132 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser His Ser Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 133 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 133 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys 180 185 190 His Leu Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser His Ser Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 134 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 134 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys 115 120 125 Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 135 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 135 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp 180 185 190 Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 136 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 136 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 137 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 137 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly 180 185 190 Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 138 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 138 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys 115 120 125 Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 139 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 139 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys 180 185 190 His Leu Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 140 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 140 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys Ala Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 141 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 141 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys 180 185 190 Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 142 <211> 279 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 142 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Trp Asp 20 25 30 Ile Met Ala Ala Ala Val Arg Met Asn Ile Gln Met Leu Leu Glu Ala 35 40 45 Ala Asp Tyr Leu Glu Arg Arg Glu Arg Glu Ala Glu His Gly Tyr Ala 50 55 60 Ser Met Leu Pro Tyr Pro Lys Lys Lys Arg Lys Val Gly Leu Glu Pro 65 70 75 80 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 85 90 95 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 100 105 110 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 115 120 125 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 130 135 140 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln 145 150 155 160 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 165 170 175 Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr 180 185 190 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 195 200 205 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 210 215 220 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu 225 230 235 240 Val Arg His Gln Arg Thr His Thr Gly Glu Gln Lys Leu Ile Ser Glu 245 250 255 Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu 275 <210> 143 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 143 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Ser Pro Glu Ser Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Ser Pro Glu Ser 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Ser Pro Glu Ser Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Ser Pro Glu Ser Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Ser Pro Glu Ser Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Ser Pro Glu Ser 225 230 235 240 Gly Lys Asn Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 144 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 144 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 145 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 145 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 146 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 146 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 147 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 147 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 148 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 148 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 149 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 149 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly 180 185 190 Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 150 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 150 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 151 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 151 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 152 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 152 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys 115 120 125 Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg 145 150 155 160 Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 153 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 153 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg 180 185 190 Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 154 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 154 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn 115 120 125 Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg 145 150 155 160 Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 155 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 155 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg 180 185 190 Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 156 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 156 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 157 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 157 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 158 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 158 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Lys Asn Ala Leu 145 150 155 160 Gln Asn His Gln Arg Thr His Thr 165 <210> 159 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 159 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Lys Asn Ala Leu 145 150 155 160 Gln Asn His Gln Arg Thr His Thr 165 <210> 160 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 160 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu 35 40 45 Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 161 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 161 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 162 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 162 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 163 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 163 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 164 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 164 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 165 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 165 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 166 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 166 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 167 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 167 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly 180 185 190 Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 168 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 168 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 169 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 169 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 170 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 170 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala 115 120 125 Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 171 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 171 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 172 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 172 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala 115 120 125 Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 173 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 173 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 174 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 174 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 175 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 175 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 176 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 176 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 177 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 177 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 178 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 178 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 179 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 179 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 180 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 180 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 181 <211> 279 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 181 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Trp Asp 20 25 30 Ile Met Ala Ala Ala Val Arg Met Asn Ile Gln Met Leu Leu Glu Ala 35 40 45 Ala Asp Tyr Leu Glu Arg Arg Glu Arg Glu Ala Glu His Gly Tyr Ala 50 55 60 Ser Met Leu Pro Tyr Pro Lys Lys Lys Arg Lys Val Gly Leu Glu Pro 65 70 75 80 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 85 90 95 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 100 105 110 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu 115 120 125 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 130 135 140 Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln 145 150 155 160 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 165 170 175 Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr 180 185 190 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 195 200 205 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 210 215 220 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 225 230 235 240 Val Arg His Gln Arg Thr His Thr Gly Glu Gln Lys Leu Ile Ser Glu 245 250 255 Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu 275 <210> 182 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 182 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys 115 120 125 Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 183 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 183 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 184 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 184 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 185 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 185 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 186 <211> 279 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 186 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Trp Asp 20 25 30 Ile Met Ala Ala Ala Val Arg Met Asn Ile Gln Met Leu Leu Glu Ala 35 40 45 Ala Asp Tyr Leu Glu Arg Arg Glu Arg Glu Ala Glu His Gly Tyr Ala 50 55 60 Ser Met Leu Pro Tyr Pro Lys Lys Lys Arg Lys Val Gly Leu Glu Pro 65 70 75 80 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 85 90 95 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 100 105 110 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu 115 120 125 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 130 135 140 Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln 145 150 155 160 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 165 170 175 Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr 180 185 190 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 195 200 205 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 210 215 220 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 225 230 235 240 Val Arg His Gln Arg Thr His Thr Gly Glu Gln Lys Leu Ile Ser Glu 245 250 255 Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu 275 <210> 187 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 187 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Ser Pro Glu Ser Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Ser Pro Glu Ser 115 120 125 Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Ser Pro Glu Ser Gly Lys Ser Phe 145 150 155 160 Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Ser Pro Glu Ser Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Ser Pro Glu Ser Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Ser Pro Glu Ser 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 188 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 188 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp His Leu 145 150 155 160 Thr Asn His Gln Arg Thr His Thr 165 <210> 189 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 189 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp His Leu Thr Asn His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 190 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 190 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Gln Ser Gly His Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp His Leu Thr Asn His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 191 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 191 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Thr Gly His Leu 145 150 155 160 Leu Glu His Gln Arg Thr His Thr 165 <210> 192 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 192 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 193 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 193 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu 35 40 45 Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 194 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 194 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser His Thr Gly His Leu Leu Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 195 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 195 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys 115 120 125 Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 196 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 196 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 197 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 197 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser His Thr Gly His Leu Leu Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 198 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 198 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 199 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 199 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 200 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 200 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Asn Ser Thr Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Asn Ser Thr Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 201 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 201 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Asn Asp Thr Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 202 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 202 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu 35 40 45 Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Asn Asp Thr Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 203 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 203 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser His Lys Asn Ala Leu Gln Asn His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 204 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 204 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser His Lys Asn Ala Leu Gln Asn His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 205 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 205 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser His Lys Asn Ala Leu Gln Asn His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 206 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 206 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys 115 120 125 Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Asn Ser Thr Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Asn Ser Thr Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 207 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 207 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Asn Ser 180 185 190 Thr Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Asn Ser Thr Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 208 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 208 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Asn Asp Thr Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 209 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 209 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp 180 185 190 Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Thr Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 210 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 210 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Asn Asp Thr Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 211 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 211 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Thr Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 212 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 212 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Lys 115 120 125 Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 213 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 213 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 214 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 214 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Lys 115 120 125 Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 215 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 215 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 180 185 190 Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 216 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 216 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser His Lys 115 120 125 Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 217 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 217 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Arg Ala Asp Asn Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser His Lys Asn Ala Leu Gln Asn His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly 180 185 190 Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 218 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 218 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 219 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 219 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser His Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 220 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 220 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 1 5 10 15 Ser His Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 221 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 221 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 222 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 222 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Thr Ser His Ser Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg 115 120 125 Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 223 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 223 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn 115 120 125 Asp Thr Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 224 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 224 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 Ala Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 225 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 225 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser His Ser Leu Thr Glu 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu Thr Glu 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 226 <211> 289 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 226 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Ala Ala Ala Val 35 40 45 Arg Met Asn Ile Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg 50 55 60 Arg Glu Arg Glu Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro 65 70 75 80 Lys Lys Lys Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys 85 90 95 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg 100 105 110 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 115 120 125 Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr 130 135 140 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 145 150 155 160 Ser Arg Asn Asp Thr Leu Thr Glu His Gln Arg Thr His Thr Gly Glu 165 170 175 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly 180 185 190 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 195 200 205 Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg 210 215 220 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 225 230 235 240 Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr 245 250 255 His Thr Gly Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys 260 265 270 Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp 275 280 285 Leu <210> 227 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 227 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Arg Ala Asn Leu Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 228 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 228 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu 145 150 155 160 Ala Glu His Gln Arg Thr His Thr 165 <210> 229 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 229 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser 1 5 10 15 Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 230 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 230 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Asn Asp Thr Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 231 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 231 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser 1 5 10 15 Lys Lys Ala Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 232 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 232 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser 1 5 10 15 Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly Ala Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 233 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 233 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 234 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 234 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 235 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 235 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu 145 150 155 160 Ala Arg His Gln Arg Thr His Thr 165 <210> 236 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 236 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 35 40 45 Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Arg Ser Asp Lys Leu Thr Glu His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu 145 150 155 160 Val Arg His Gln Arg Thr His Thr 165 <210> 237 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 237 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 35 40 45 Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 145 150 155 160 Arg Ala His Gln Arg Thr His Thr 165 <210> 238 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 238 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 239 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 239 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 1 5 10 15 Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 240 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 240 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asn Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu 145 150 155 160 Ala Glu His Gln Arg Thr His Thr 165 <210> 241 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 241 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Asn Asp Ala Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 115 120 125 Ser Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 242 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 242 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 1 5 10 15 Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 35 40 45 Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln 115 120 125 Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 243 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 243 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Thr Gly Ala Leu 35 40 45 Thr Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp 115 120 125 Pro Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Lys Asn Ser Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 244 <211> 168 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 244 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg 1 5 10 15 Ser Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 20 25 30 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Ser Arg Arg Thr Cys 35 40 45 Arg Ala His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro 50 55 60 Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln 65 70 75 80 Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys 85 90 95 Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr 100 105 110 Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr 115 120 125 Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro 130 135 140 Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Asn Ser Thr Leu 145 150 155 160 Thr Glu His Gln Arg Thr His Thr 165 <210> 245 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 245 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Arg Ala Asn Leu Arg Ala His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 246 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 246 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Lys Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 247 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 247 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 248 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 248 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Asn Asp Thr Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro 115 120 125 Gly His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg Ala His Leu Glu 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 249 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 249 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Ser Lys Lys Ala Leu Thr Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 250 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 250 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg 115 120 125 Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly Ala Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Ser Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 251 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 251 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 252 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 252 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 253 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 253 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Asp Cys Arg Asp Leu Ala Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 254 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 254 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Asn Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Thr 145 150 155 160 Glu His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 255 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 255 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 256 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 256 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 257 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 257 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 258 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 258 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Gln Ser Gly Asn Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser 115 120 125 Ser Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Ser Asn Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Ser Lys Lys His Leu Ala Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 259 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 259 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Arg Asn Asp Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser 115 120 125 Gly Ser Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Arg Ser Asp Lys Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 260 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 260 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Asp Pro Gly His Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Arg 115 120 125 Ala His Leu Glu Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Cys Arg Asp Leu Ala 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 261 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 261 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Thr Thr Gly Ala Leu Thr Glu His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Gln Ser Gly Asp Leu Arg 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Thr Lys Asn Ser Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 262 <211> 319 <212> PRT <213> Artificial Sequence <220> <223> synthetic construct <400> 262 Met His His His His His His Gly Tyr Gly Arg Lys Lys Arg Arg Gln 1 5 10 15 Arg Arg Arg Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala Pro Cys Gln 20 25 30 Pro Met Lys Arg Leu Thr Leu Gly Asn Asp Ile Met Pro Lys Lys Lys 35 40 45 Arg Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu 50 55 60 Cys Gly Lys Ser Phe Ser Arg Ser Asp Asp Leu Val Arg His Gln Arg 65 70 75 80 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 85 90 95 Phe Ser Ser Arg Arg Thr Cys Arg Ala His Gln Arg Thr His Thr Gly 100 105 110 Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Arg Ser 115 120 125 Asp Asp Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr 130 135 140 Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly Ser Leu Val 145 150 155 160 Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu 165 170 175 Cys Gly Lys Ser Phe Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg 180 185 190 Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser 195 200 205 Phe Ser Gln Asn Ser Thr Leu Thr Glu His Gln Arg Thr His Thr Gly 210 215 220 Gly Gly Ser Gly Gly Ser Glu Phe Gly Arg Ala Asp Ala Leu Asp Asp 225 230 235 240 Phe Asp Leu Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu 245 250 255 Asp Met Leu Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu 260 265 270 Gly Ser Asp Ala Leu Asp Asp Phe Asp Leu Asp Met Leu Ile Asn Gly 275 280 285 Ser Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile 290 295 300 Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 305 310 315 <210> 263 <211> 333 <212> PRT <213> Artificial Sequence <220> <223> Synthetic construct <400> 263 Met Gly Gly Arg Arg Val Arg Trp Glu Val Tyr Ile Ser Arg Ala Leu 1 5 10 15 Pro Ile Ser Asp Arg Asp Leu Pro Ile Ser Asp Arg Asp Arg Arg Arg 20 25 30 Ala Arg Leu Val Asn Arg Gln Ile Ala Trp Arg Arg His Pro Arg Cys 35 40 45 Phe Asp Leu His Arg Arg His Arg Asp Arg Ser Ser Leu Arg Thr Leu 50 55 60 Ala Phe Lys Leu Lys Leu Gly Thr Glu Leu Gly Ser Thr Ser Pro Val 65 70 75 80 Trp Trp Asn Ser Ala Asp Ile Met Ala Ala Ala Val Arg Met Asn Ile 85 90 95 Gln Met Leu Leu Glu Ala Ala Asp Tyr Leu Glu Arg Arg Glu Arg Glu 100 105 110 Ala Glu His Gly Tyr Ala Ser Met Leu Pro Tyr Pro Lys Lys Lys Arg 115 120 125 Lys Val Gly Leu Glu Pro Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 130 135 140 Gly Lys Ser Phe Ser Arg Ser Asp Asn Leu Val Arg His Gln Arg Thr 145 150 155 160 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 165 170 175 Ser Arg Ser Asp Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 180 185 190 Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe Ser Thr Ser Gly 195 200 205 His Leu Val Arg His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys 210 215 220 Cys Pro Glu Cys Gly Lys Ser Phe Ser Asp Pro Gly Asn Leu Val Arg 225 230 235 240 His Gln Arg Thr His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys 245 250 255 Gly Lys Ser Phe Ser Gln Ser Ser Ser Leu Val Arg His Gln Arg Thr 260 265 270 His Thr Gly Glu Lys Pro Tyr Lys Cys Pro Glu Cys Gly Lys Ser Phe 275 280 285 Ser Thr Ser Gly Glu Leu Val Arg His Gln Arg Thr His Thr Gly Glu 290 295 300 Gln Lys Leu Ile Ser Glu Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu 305 310 315 320 Glu Asp Leu Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 325 330 <210> 264 <211> 4513 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 264 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt cgagctcggt accgtatacc 420 tcgagcccgg ggaaaagcca tataaatgcc ccgagtgcgg caaatcattc agccaaagta 480 gcaacttagt aagacaccag cgcacccata ccggtaagaa aactagtctt aagctcgagc 540 ccggggaaaa accctataaa tgccccgagt gtggtaagtc attctctcaa agcggggatt 600 taagaagaca ccagagaacc cacaccggta agaaaactag tggcgcgccc tcgagcccgg 660 ggagaaacct tataaatgcc cagaatgcgg gaaatcgttc agtcaaagag cacatttaga 720 aagacatcaa cggacccaca ccggtaagaa aactagtcct aggctcgagc ccggggaaaa 780 accttacaag tgccctgagt gcggcaagag cttctctcaa tcaagttcat tagtaagaca 840 ccagaggact cataccggta agaaaactag tcctcagcct cgagcccggg gagaagcctt 900 ataagtgccc tgagtgtggc aaaagcttca gcgatcctgg aaatttagta agacaccaac 960 gcacccacac cggtaagaaa actagtatgc atctcgagcc cggggaaaaa ccgtataaat 1020 gtcctgagtg cggtaagtct ttttccgact gtagagactt agcgagacac caacgtactc 1080 ataccggtaa aaagactagt tgtacactcg agcccgggga aaaaccgtac aagtgtcctg 1140 agtgcgggaa gagtttctcc gatccgggcc acttagtaag acatcagagg acacataccg 1200 gtaaaaagac tagtttcgaa ctcgagcccg gggagaaacc atacaaatgc cccgagtgtg 1260 gaaagtcatt tagtgatcca ggcgcattag taagacatca gcggacacat accggtaaga 1320 aaactagtga attcctcgag cccggggaga agccatataa atgtcccgag tgtggcaagt 1380 ccttttctag atcagataat ttagtaagac atcagagaac gcacaccggt aaaaagacta 1440 gtcaattgct cgagcccggg gagaagccat acaagtgtcc cgaatgcggg aagtcattct 1500 ccagaagtga cgatttagta agacatcagc gcacgcacac cggtaagaaa actagtccat 1560 ggctcgagcc cggggagaag ccctacaagt gtccagaatg cggaaagagt ttctccagaa 1620 gtgacaaatt agtaagacac cagagaaccc ataccggtaa gaaaactagt catatgctcg 1680 agcccgggga gaagccgtac aagtgccctg aatgtggtaa gtcattttcg agaagtgatg 1740 aattagtaag acaccagcgg actcataccg gtaaaaagac tagtgctagc ctcgagcccg 1800 gggagaagcc ctataaatgt ccagaatgtg gaaagtcctt tagcacgtca gggaacttag 1860 taagacacca gcgaactcat accggtaaga aaactagttt aattaactcg agcccgggga 1920 gaaaccatac aagtgtccag agtgcgggaa aagctttagt acaagcggtg agttagtaag 1980 acaccaacga acacacaccg gtaaaaagac tagtgtttaa acctcgagcc cggggaaaag 2040 ccctacaagt gcccggaatg cggcaagtct tttagcacca gcggacattt agtaagacac 2100 cagagaaccc acaccggtaa aaagactagt ccgcggctcg agcccgggga aaagccctac 2160 aagtgtcctg agtgcggaaa gtctttctcc actagcggtt cattagtaag acaccagagg 2220 acacacaccg gtaaaaagac tagtgcatgc gtcgactgca gaggcctgca tgcaagcttg 2280 gcgtaatcat ggtcatagct gtttcctgtg tgaaattgtt atccgctcac aattccacac 2340 aacatacgag ccggaagcat aaagtgtaaa gcctggggtg cctaatgagt gagctaactc 2400 acattaattg cgttgcgctc actgcccgct ttccagtcgg gaaacctgtc gtgccagctg 2460 cattaatgaa tcggccaacg cgcggggaga ggcggtttgc gtattgggcg ctcttccgct 2520 tcctcgctca ctgactcgct gcgctcggtc gttcggctgc ggcgagcggt atcagctcac 2580 tcaaaggcgg taatacggtt atccacagaa tcaggggata acgcaggaaa gaacatgtga 2640 gcaaaaggcc agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccat 2700 aggctccgcc cccctgacga gcatcacaaa aatcgacgct caagtcagag gtggcgaaac 2760 ccgacaggac tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct 2820 gttccgaccc tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg 2880 ctttctcata gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg 2940 ggctgtgtgc acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt 3000 cttgagtcca acccggtaag acacgactta tcgccactgg cagcagccac tggtaacagg 3060 attagcagag cgaggtatgt aggcggtgct acagagttct tgaagtggtg gcctaactac 3120 ggctacacta gaagaacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga 3180 aaaagagttg gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt 3240 gtttgcaagc agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt 3300 tctacggggt ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga 3360 ttatcaaaaa ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc 3420 taaagtatat atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct 3480 atctcagcga tctgtctatt tcgttcatcc atagttgcct gactccccgt cgtgtagata 3540 actacgatac gggagggctt accatctggc cccagtgctg caatgatacc gcgagaccca 3600 cgctcaccgg ctccagattt atcagcaata aaccagccag ccggaagggc cgagcgcaga 3660 agtggtcctg caactttatc cgcctccatc cagtctatta attgttgccg ggaagctaga 3720 gtaagtagtt cgccagttaa tagtttgcgc aacgttgttg ccattgctac aggcatcgtg 3780 gtgtcacgct cgtcgtttgg tatggcttca ttcagctccg gttcccaacg atcaaggcga 3840 gttacatgat cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt 3900 gtcagaagta agttggccgc agtgttatca ctcatggtta tggcagcact gcataattct 3960 cttactgtca tgccatccgt aagatgcttt tctgtgactg gtgagtactc aaccaagtca 4020 ttctgagaat agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat acgggataat 4080 accgcgccac atagcagaac tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga 4140 aaactctcaa ggatcttacc gctgttgaga tccagttcga tgtaacccac tcgtgcaccc 4200 aactgatctt cagcatcttt tactttcacc agcgtttctg ggtgagcaaa aacaggaagg 4260 caaaatgccg caaaaaaggg aataagggcg acacggaaat gttgaatact catactcttc 4320 ctttttcaat attattgaag catttatcag ggttattgtc tcatgagcgg atacatattt 4380 gaatgtattt agaaaaataa acaaataggg gttccgcgca catttccccg aaaagtgcca 4440 cctgacgtct aagaaaccat tattatcatg acattaacct ataaaaatag gcgtatcacg 4500 aggccctttc gtc 4513 <210> 265 <211> 4442 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 265 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt cgagctcggt acctcgcgaa 420 tgcatctaga tgtatacctc gagcccgggg agaagcccta taaatgccct gaatgcggga 480 aatctttctc ttctaagaag gcactcacag aacaccagcg gacacacacc ggtaaaaaaa 540 ctagtcttaa gctcgagccc ggggaaaagc cctacaagtg ccccgaatgc gggaagtctt 600 ttagtcagag tggaaatctt accgagcacc agagaacaca caccggtaag aagactagtg 660 gcgcgccctc gagcccgggg agaagccata caagtgccct gaatgtggca agtccttttc 720 aagagccgat aacctgacag aacaccaaag gacgcatacc ggtaagaaaa ctagtcctag 780 gctcgagccc ggggagaagc cctataaatg ccctgaatgt ggcaagagct tcagtactag 840 cgggaatctc actgaacatc agcgaactca taccggtaaa aaaactagtc ctcagcctcg 900 agcccgggga aaaaccatac aagtgccctg agtgcggcaa gagttttagt acctcacact 960 ctcttacaga acatcagcga acccacaccg gtaaaaaaac tagtatgcat ctcgagcccg 1020 gggagaaacc atacaaatgt cccgaatgtg gcaagagttt cagcagtaaa aagcatctcg 1080 ctgagcatca gagaactcac accggtaaaa agactagttg tacactcgag cccggggaaa 1140 agccctacaa atgccccgaa tgtggtaagt ctttttctag gaacgacacc ttgacagaac 1200 accagcggac ccacaccggt aagaagacta gtgaattcct cgagcccggg gagaagcctt 1260 ataagtgccc cgaatgtgga aagagtttct ctactaagaa tagcctgacc gagcaccagc 1320 gcactcacac cggtaagaaa actagtcaat tgctcgagcc cggggagaag ccctataaat 1380 gccctgaatg cgggaaatct ttctctcaat caggccacct cacagaacac cagcggacac 1440 acaccggtaa aaaaactagt ccatggctcg agcccgggga gaaaccctat aagtgtcccg 1500 aatgcgggaa atcattctct catacagggc atctgctcga acatcaaagg acgcacaccg 1560 gtaaaaagac tagtcatatg ctcgagcccg gggaaaagcc ttacaaatgc cccgaatgtg 1620 ggaagagttt cagccggtct gataagctga ccgaacacca gagaactcat accggtaaaa 1680 aaactagtgc tagcctcgag cccggggaaa agccctacaa gtgccctgag tgtgggaagt 1740 ccttttcttc aagacgcacg tgccgcgctc accagcggac acataccggt aagaaaacta 1800 gtttaattaa ctcgagcccg gggagaaacc atacaaatgt cccgaatgtg gcaagtcctt 1860 ctcacagaac tctactttga ccgagcatca gagaactcac accggtaaga agactagtcc 1920 gcggctcgag cccggggaaa agccttataa gtgccccgaa tgcggaaaga gcttctcaag 1980 gaatgatgca cttaccgagc atcaaaggac tcataccggt aaaaaaacta gtgcatgctt 2040 cgaactcgag cccggggaaa agccctataa gtgtcccgaa tgcggcaaga gttttagtac 2100 tactggcgca ctcacagaac accagcgcac tcacaccggt aagaaaacta gtgaaagtcc 2160 tctccactga ctgtagcctc caattcactg gagatctgac acaagcttgg cgtaatcatg 2220 gtcatagctg tttcctgtgt gaaattgtta tccgctcaca attccacaca acatacgagc 2280 cggaagcata aagtgtaaag cctggggtgc ctaatgagtg agctaactca cattaattgc 2340 gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat 2400 cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac 2460 tgactcgctg cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt 2520 aatacggtta tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaggcca 2580 gcaaaaggcc aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc 2640 ccctgacgag catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact 2700 ataaagatac caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct 2760 gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag 2820 ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca 2880 cgaacccccc gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa 2940 cccggtaaga cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc 3000 gaggtatgta ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag 3060 aagaacagta tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg 3120 tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca 3180 gcagattacg cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc 3240 tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag 3300 gatcttcacc tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata 3360 tgagtaaact tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat 3420 ctgtctattt cgttcatcca tagttgcctg actccccgtc gtgtagataa ctacgatacg 3480 ggagggctta ccatctggcc ccagtgctgc aatgataccg cgagacccac gctcaccggc 3540 tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa gtggtcctgc 3600 aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc 3660 gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc 3720 gtcgtttggt atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc 3780 ccccatgttg tgcaaaaaag cggttagctc cttcggtcct ccgatcgttg tcagaagtaa 3840 gttggccgca gtgttatcac tcatggttat ggcagcactg cataattctc ttactgtcat 3900 gccatccgta agatgctttt ctgtgactgg tgagtactca accaagtcat tctgagaata 3960 gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata ccgcgccaca 4020 tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag 4080 gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc 4140 agcatctttt actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc 4200 aaaaaaggga ataagggcga cacggaaatg ttgaatactc atactcttcc tttttcaata 4260 ttattgaagc atttatcagg gttattgtct catgagcgga tacatatttg aatgtattta 4320 gaaaaataaa caaatagggg ttccgcgcac atttccccga aaagtgccac ctgacgtcta 4380 agaaaccatt attatcatga cattaaccta taaaaatagg cgtatcacga ggccctttcg 4440 tc 4442 <210> 266 <211> 4376 <212> DNA <213> Artificial Sequence <220> <223> synthetic contruct <400> 266 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatgcg gtgtgaaata ccgcacagat gcgtaaggag aaaataccgc atcaggcgcc 240 attcgccatt caggctgcgc aactgttggg aagggcgatc ggtgcgggcc tcttcgctat 300 tacgccagct ggcgaaaggg ggatgtgctg caaggcgatt aagttgggta acgccagggt 360 tttcccagtc acgacgttgt aaaacgacgg ccagtgaatt cgagctcggt accgtatacc 420 tcgagcccgg ggagaagcca tacaaatgcc ctgagtgtgg aaagtcattt agccagcgag 480 ctaatctgcg ggcccaccag cggacccaca ccggtaagaa gactagtctt aagctcgagc 540 ccggggagaa gccatacaaa tgtccagaat gtggaaagtc cttctctgat agtggcaacc 600 tcagagtgca tcagcgaaca cataccggta agaagactag tggcgcgccc tcgagcccgg 660 ggaaaagcca tataagtgcc ctgagtgtgg aaagagcttc agtaggaagg ataaccttaa 720 aaaccaccaa agaacccaca ccggtaagaa gactagtcct aggctcgagc ccggggaaaa 780 gccatataaa tgtcccgagt gcggcaaatc cttctctacc actggcaacc tcacagtgca 840 tcaacggact cacaccggta aaaagactag tcctcagcct cgagcccggg gaaaagccct 900 ataaatgtcc cgagtgcgga aagtcttttt ccagccctgc cgacctgaca cgccaccaac 960 gaacgcacac cggtaagaag actagtatgc atctcgagcc cggggaaaag ccgtacaaat 1020 gtccagagtg tggaaaatcc ttttctgata aaaaggacct gacacggcat cagcgaaccc 1080 acaccggtaa aaagactagt tgtacactcg agcccgggga gaaaccttat aaatgcccag 1140 aatgcggtaa aagtttcagc aggacggata ccttgcggga tcatcagaga acccacaccg 1200 gtaaaaaaac tagtgaattc ctcgagcccg gggaaaaacc atacaagtgc cccgagtgtg 1260 gcaagagctt tagtacccac ctcgacctga ttagacacca gcgcacccac accggtaaga 1320 aaactagtca attgctcgag cccggggaaa agccctataa gtgcccagag tgcgggaaat 1380 cattctcaca gctggcacat cttagagccc accagcggac ccacaccggt aagaagacta 1440 gtccatggct cgagcccggg gagaaaccct ataagtgccc tgaatgcggc aagtctttca 1500 gtgagcggtc acatctccga gagcaccagc gaacgcacac cggtaaaaag actagtcata 1560 tgctcgagcc cggggaaaaa ccctacaagt gccctgagtg tggaaagtca tttagtcgct 1620 ccgaccacct gaccaaccat cagcggactc acaccggtaa gaaaactagt gctagcctcg 1680 agcccgggga gaaaccttac aagtgccccg agtgcggcaa gagtttcagc cacaggacca 1740 ccctgacaaa ccaccagagg acccacaccg gtaaaaagac tagtttaatt aactcgagcc 1800 cggggagaaa ccttataagt gtcctgagtg cggcaaaagt ttctctcaaa agtcctccct 1860 tattgcccat caaaggaccc ataccggtaa gaagactagt gtttaaacct cgagcccggg 1920 gagaagccct ataaatgtcc cgagtgcgga aagtccttct cacggcgcga tgaattgaac 1980 gtccatcaga gaacacacac cggtaaaaaa actagtccgc ggctcgagcc cggggaaaaa 2040 ccttataagt gtcccgagtg cggcaagagt ttcagtcaca aaaacgcact tcagaatcat 2100 cagaggacac ataccggtaa gaaaactagt gcatgcaagc ttggcgtaat catggtcata 2160 gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac gagccggaag 2220 cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa ttgcgttgcg 2280 ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat gaatcggcca 2340 acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc 2400 gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg cggtaatacg 2460 gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaag gccagcaaaa 2520 ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc gcccccctga 2580 cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag gactataaag 2640 ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga ccctgccgct 2700 taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc atagctcacg 2760 ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc 2820 ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt ccaacccggt 2880 aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca gagcgaggta 2940 tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca ctagaagaac 3000 agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag ttggtagctc 3060 ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca agcagcagat 3120 tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc 3180 tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa aaaggatctt 3240 cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta tatatgagta 3300 aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag cgatctgtct 3360 atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga tacgggaggg 3420 cttaccatct ggccccagtg ctgcaatgat accgcgagac ccacgctcac cggctccaga 3480 tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc ctgcaacttt 3540 atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta gttcgccagt 3600 taatagtttg cgcaacgttg ttgccattgc tacaggcatc gtggtgtcac gctcgtcgtt 3660 tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat gatcccccat 3720 gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa gtaagttggc 3780 cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg tcatgccatc 3840 cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag aatagtgtat 3900 gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc cacatagcag 3960 aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct caaggatctt 4020 accgctgttg agatccagtt cgatgtaacc cactcgtgca cccaactgat cttcagcatc 4080 ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa 4140 gggaataagg gcgacacgga aatgttgaat actcatactc ttcctttttc aatattattg 4200 aagcatttat cagggttatt gtctcatgag cggatacata tttgaatgta tttagaaaaa 4260 taaacaaata ggggttccgc gcacatttcc ccgaaaagtg ccacctgacg tctaagaaac 4320 cattattatc atgacattaa cctataaaaa taggcgtatc acgaggccct ttcgtc 4376 <210> 267 <211> 57 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 267 tcgacaggcc caggcggccc tcgaggatat catgatgact agtggccagg ccggccc 57 <210> 268 <211> 57 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 268 aattgggccg gcctggccac tagtcatcat gatatcctcg agggccgcct gggcctg 57 <210> 269 <211> 6699 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 269 gcttgcatgc aacttctttt cttttttttt cttttctctc tcccccgttg ttgtctcacc 60 atatccgcaa tgacaaaaaa aatgatggaa gacactaaag gaaaaaatta acgacaaaga 120 cagcaccaac agatgtcgtt gttccagagc tgatgagggg tatcttcgaa cacacgaaac 180 tttttccttc cttcattcac gcacactact ctctaatgag caacggtata cggccttcct 240 tccagttact tgaatttgaa ataaaaaaag tttgccgctt tgctatcaag tataaataga 300 cctgcaatta ttaatctttt gtttcctcgt cattgttctc gttccctttc ttccttgttt 360 ctttttctgc acaatatttc aagctatacc aagcatacaa tcaactccaa gctttgcaaa 420 gatggataaa gcggaattaa ttcccgagcc tccaaaaaag aagagaaagg tcgaattggg 480 taccgccgcc aattttaatc aaagtgggaa tattgctgat agctcattgt ccttcacttt 540 cactaacagt agcaacggtc cgaacctcat aacaactcaa acaaattctc aagcgctttc 600 acaaccaatt gcctcctcta acgttcatga taacttcatg aataatgaaa tcacggctag 660 taaaattgat gatggtaata attcaaaacc actgtcacct ggttggacgg accaaactgc 720 gtataacgcg tttggaatca ctacagggat gtttaatacc actacaatgg atgatgtata 780 taactatcta ttcgatgatg aagatacccc accaaaccca aaaaaagaga tctctcgaca 840 ggcccaggcg gccctcgagg atatcatgat gactagtggc caggccggcc caattccaga 900 tctatgaatc gtagatactg aaaaaccccg caagttcact tcaactgtgc atcgtgcacc 960 atctcaattt ctttcattta tacatcgttt tgccttcttt tatgtaacta tactcctcta 1020 agtttcaatc ttggccatgt aacctctgat ctatagaatt ttttaaatga ctagaattaa 1080 tgcccatctt ttttttggac ctaaattctt catgaaaata tattacgagg gcttattcag 1140 aagctttgga cttcttcgcc agaggtttgg tcaagtctcc aatcaaggtt gtcggcttgt 1200 ctaccttgcc agaaatttac gaaaagatgg aaaagggtca aatcgttggt agatacgttg 1260 ttgacacttc taaataagcg aatttcttat gatttatgat ttttattatt aaataagtta 1320 taaaaaaaat aagtgtatac aaattttaaa gtgactctta ggttttaaaa cgaaaattct 1380 tattcttgag taactctttc ctgtaggtca ggttgctttc tcaggtatag catgaggtcg 1440 ctcttattga ccacacctct accggcatgc cggtcgaaat tcccctaccc tatgaacata 1500 ttccattttg taatttcgtg tcgtttctat tatgaatttc atttataaag tttatgtaca 1560 aatatcataa aaaaagagaa tctttttaag caaggatttt cttaacttct tcggcgacag 1620 catcaccgac ttcggtggta ctgttggaac cacctaaatc accagttctg atacctgcat 1680 ccaaaacctt tttaactgca tcttcaatgg ccttaccttc ttcaggcaag ttcaatgaca 1740 atttcaacat cattgcagca gacaagatag tggcgatagg gtcaacctta ttctttggca 1800 aatctggagc agaaccgtgg catggttcgt acaaaccaaa tgcggtgttc ttgtctggca 1860 aagaggccaa ggacgcagat ggcaacaaac ccaaggaacc tgggataacg gaggcttcat 1920 cggagatgat atcaccaaac atgttgctgg tgattataat accatttagg tgggttgggt 1980 tcttaactag gatcatggcg gcagaatcaa tcaattgatg ttgaaccttc aatgtaggaa 2040 attcgttctt gatggtttcc tccacagttt ttctccataa tcttgaagag gccaaaacat 2100 tagctttatc caaggaccaa ataggcaatg gtggctcatg ttgtagggcc atgaaagcgg 2160 ccattcttgt gattctttgc acttctggaa cggtgtattg ttcactatcc caagcgacac 2220 catcaccatc gtcttccttt ctcttaccaa agtaaatacc tcccactaat tctctgacaa 2280 caacgaagtc agtaccttta gcaaattgtg gcttgattgg agataagtct aaaagagagt 2340 cggatgcaaa gttacatggt cttaagttgg cgtacaattg aagttcttta cggattttta 2400 gtaaaccttg ttcaggtcta acactacctg taccccattt aggaccaccc acagcaccta 2460 acaaaacggc atcaaccttc ttggaggctt ccagcgcctc atctggaagt gggacacctg 2520 tagcatcgat agcagcacca ccaattaaat gattttcgaa atcgaacttg acattggaac 2580 gaacatcaga aatagcttta agaaccttaa tggcttcggc tgtgatttct tgaccaacgt 2640 ggtcacctgg caaaacgacg atcttcttag gggcagacat tagaatggta tatccttgaa 2700 atatatatat atattgctga aatgtaaaag gtaagaaaag ttagaaagta agacgattgc 2760 taaccaccta ttggaaaaaa caataggtcc ttaaataata ttgtcaactt caagtattgt 2820 gatgcaagca tttagtcatg aacgcttctc tattctatat gaaaagccgg ttccggcctc 2880 tcacctttcc tttttctccc aatttttcag ttgaaaaagg tatatgcgtc aggcgacctc 2940 tgaaattaac aaaaaatttc cagtcatcga atttgattct gtgcgatagc gcccctgtgt 3000 gttctcgtta tgttgaggaa aaaaataatg gttgctaaga gattcgaact cttgcatctt 3060 acgatacctg agtattccca cagttgggga tctcgactct agctagagga tcaattcgta 3120 atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc cacacaacat 3180 acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgaggt aactcacatt 3240 aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctggatta 3300 atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc 3360 gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa 3420 ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa 3480 aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt tccataggct 3540 ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc gaaacccgac 3600 aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc 3660 gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg tggcgctttc 3720 tcatagctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca agctgggctg 3780 tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact atcgtcttga 3840 gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta acaggattag 3900 cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta actacggcta 3960 cactagaagg acagtatttg gtatctgcgc tctgctgaag ccagttacct tcggaaaaag 4020 agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt tttttgtttg 4080 caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga tcttttctac 4140 ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc 4200 aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag 4260 tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc 4320 agcgatctgt ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac 4380 gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc 4440 accggctcca gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg 4500 tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag 4560 tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca tcgtggtgtc 4620 acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac 4680 atgatccccc atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag 4740 aagtaagttg gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac 4800 tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg 4860 agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg ataataccgc 4920 gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact 4980 ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg 5040 atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa 5100 tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt 5160 tcaatattat tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg 5220 tatttagaaa aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccacctga 5280 cgtctaagaa accattatta tcatgacatt aacctataaa aataggcgta tcacgaggcc 5340 ctttcgtctc gcgcgtttcg gtgatgacgg tgaaaacctc tgacacatgc agctcccgga 5400 gacggtcaca gcttgtctgt aagcggatgc cgggagcaga caagcccgtc agggcgcgtc 5460 agcgggtgtt ggcgggtgtc ggggctggct taactatgcg gcatcagagc agattgtact 5520 gagagtgcac cataacgcat ttaagcataa acacgcacta tgccgttctt ctcatgtata 5580 tatatataca ggcaacacgc agatataggt gcgacgtgaa cagtgagctg tatgtgcgca 5640 gctcgcgttg cattttcgga agcgctcgtt ttcggaaacg ctttgaagtt cctattccga 5700 agttcctatt ctctagctag aaagtatagg aacttcagag cgcttttgaa aaccaaaagc 5760 gctctgaaga cgcactttca aaaaaccaaa aacgcaccgg actgtaacga gctactaaaa 5820 tattgcgaat accgcttcca caaacattgc tcaaaagtat ctctttgcta tatatctctg 5880 tgctatatcc ctatataacc tacccatcca cctttcgctc cttgaacttg catctaaact 5940 cgacctctac attttttatg tttatctcta gtattactct ttagacaaaa aaattgtagt 6000 aagaactatt catagagtga atcgaaaaca atacgaaaat gtaaacattt cctatacgta 6060 gtatatagag acaaaataga agaaaccgtt cataattttc tgaccaatga agaatcatca 6120 acgctatcac tttctgttca caaagtatgc gcaatccaca tcggtataga atataatcgg 6180 ggatgccttt atcttgaaaa aatgcacccg cagcttcgct agtaatcagt aaacgcggga 6240 agtggagtca ggcttttttt atggaagaga aaatagacac caaagtagcc ttcttctaac 6300 cttaacggac ctacagtgca aaaagttatc aagagactgc attatagagc gcacaaagga 6360 gaaaaaaagt aatctaagat gctttgttag aaaaatagcg ctctcgggat gcatttttgt 6420 agaacaaaaa agaagtatag attctttgtt ggtaaaatag cgctctcgcg ttgcatttct 6480 gttctgtaaa aatgcagctc agattctttg tttgaaaaat tagcgctctc gcgttgcatt 6540 tttgttttac aaaaatgaag cacagattct tcgttggtaa aatagcgctt tcgcgttgca 6600 tttctgttct gtaaaaatgc agctcagatt ctttgtttga aaaattagcg ctctcgcgtt 6660 gcatttttgt tctacaaaat gaagcacaga tgcttcgtt 6699 <210> 270 <211> 6481 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 270 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatcga ctacgtcgta aggccgtttc tgacagagta aaattcttga gggaactttc 240 accattatgg gaaatggttc aagaaggtat tgacttaaac tccatcaaat ggtcaggtca 300 ttgagtgttt tttatttgtt gtattttttt ttttttagag aaaatcctcc aatatcaaat 360 taggaatcgt agtttcatga ttttctgtta cacctaactt tttgtgtggt gccctcctcc 420 ttgtcaatat taatgttaaa gtgcaattct ttttccttat cacgttgagc cattagtatc 480 aatttgctta cctgtattcc tttactatcc tcctttttct ccttcttgat aaatgtatgt 540 agattgcgta tatagtttcg tctaccctat gaacatattc cattttgtaa tttcgtgtcg 600 tttctattat gaatttcatt tataaagttt atgtacaaat atcataaaaa aagagaatct 660 ttttaagcaa ggattttctt aacttcttcg gcgacagcat caccgacttc ggtggtactg 720 ttggaaccac ctaaatcacc agttctgata cctgcatcca aaaccttttt aactgcatct 780 tcaatggcct taccttcttc aggcaagttc aatgacaatt tcaacatcat tgcagcagac 840 aagatagtgg cgatagggtc aaccttattc tttggcaaat ctggagcaga accgtggcat 900 ggttcgtaca aaccaaatgc ggtgttcttg tctggcaaag aggccaagga cgcagatggc 960 aacaaaccca aggaacctgg gataacggag gcttcatcgg agatgatatc accaaacatg 1020 ttgctggtga ttataatacc atttaggtgg gttgggttct taactaggat catggcggca 1080 gaatcaatca attgatgttg aaccttcaat gtagggaatt cgttcttgat ggtttcctcc 1140 acagtttttc tccataatct tgaagaggcc aaaacattag ctttatccaa ggaccaaata 1200 ggcaatggtg gctcatgttg tagggccatg aaagcggcca ttcttgtgat tctttgcact 1260 tctggaacgg tgtattgttc actatcccaa gcgacaccat caccatcgtc ttcctttctc 1320 ttaccaaagt aaatacctcc cactaattct ctgacaacaa cgaagtcagt acctttagca 1380 aattgtggct tgattggaga taagtctaaa agagagtcgg atgcaaagtt acatggtctt 1440 aagttggcgt acaattgaag ttctttacgg atttttagta aaccttgttc aggtctaaca 1500 ctaccggtac cccatttagg accacccaca gcacctaaca aaacggcatc aaccttcttg 1560 gaggcttcca gcgcctcatc tggaagtggg acacctgtag catcgatagc agcaccacca 1620 attaaatgat tttcgaaatc gaacttgaca ttggaacgaa catcagaaat agctttaaga 1680 accttaatgg cttcggctgt gatttcttga ccaacgtggt cacctggcaa aacgacgatc 1740 ttcttagggg cagacatagg ggcagacatt agaatggtat atccttgaaa tatatatata 1800 tattgctgaa atgtaaaagg taagaaaagt tagaaagtaa gacgattgct aaccacctat 1860 tggaaaaaac aataggtcct taaataatat tgtcaacttc aagtattgtg atgcaagcat 1920 ttagtcatga acgcttctct attctatatg aaaagccggt tccggcctct cacctttcct 1980 ttttctccca atttttcagt tgaaaaaggt atatgcgtca ggcgacctct gaaattaaca 2040 aaaaatttcc agtcatcgaa tttgattctg tgcgatagcg cccctgtgtg ttctcgttat 2100 gttgaggaaa aaaataatgg ttgctaagag attcgaactc ttgcatctta cgatacctga 2160 gtattcccac agttaactgc ggtcaagata tttcttgaat caggcgccgc atgccggtag 2220 aggtgtggtc aataagagcg acctcatgct atacctgaga aagcaacctg acctacagga 2280 aagagttact caagaataag aattttcgtt ttaaaaccta agagtcactt taaaatttgt 2340 atacacttat tttttttata acttatttaa taataaaaat cataaatcat aagaaattcg 2400 cttatttaga agtgtcaaca acgtatctac caacgatttg acccttttcc atcttttcgt 2460 aaatttctgg caaggtagac aagccgacaa ccttgattgg agacttgacc aaacctctgg 2520 cgaagaagtc caaagcttct gaataagccc tcgtaatata ttttcatgaa gaatttaggt 2580 ccaaaaaaaa gatgggcatt aattctagtc atttaaaaaa ttctatagat cagaggttac 2640 atggccaaga ttgaaactta gaggagtata gttacataaa agaaggcaaa acgatgtata 2700 aatgaaagaa attgagatgg tgcacgatgc acagttgaag tgaacttgcg gggtttttca 2760 gtatctacga ttcatagatc tggaattggg ccggcctggc cactagtcat catgatatcc 2820 tcgagggccg cctgggcctg tcgagagatc tctttttttg ggtttggtgg ggtatcttca 2880 tcatcgaata gatagttata tacatcatcc attgtagtgg tattaaacat ccctgtagtg 2940 attccaaacg cgttatacgc agtttggtcc gtccaaccag gtgacagtgg ttttgaatta 3000 ttaccatcat caattttact agccgtgatt tcattattca tgaagttatc atgaacgtta 3060 gaggaggcaa ttggttgtga aagcgcttga gaatttgttt gagttgttat gaggttcgga 3120 ccgttgctac tgttagtgaa agtgaaggac aatgagctat cagcaatatt cccactttga 3180 ttaaaattgg cggcggtacc caattcgacc tttctcttct tttttggagg ctcgggaatt 3240 aattccgctt tatccatctt tgcaaagctt ggagttgatt gtatgcttgg tatagcttga 3300 aatattgtgc agaaaaagaa acaaggaaga aagggaacga gaacaatgac gaggaaacaa 3360 aagattaata attgcaggtc tatttatact tgatagcaaa gcggcaaact ttttttattt 3420 caaattcaag taactggaag gaaggccgta taccgttgct cattagagag tagtgtgcgt 3480 gaatgaagga aggaaaaagt ttcgtgtgtt cgaagatacc cctcatcagc tctggaacaa 3540 cgacatctgt tggtgctgtc tttgtcgtta attttttcct ttagtgtctt ccatcatttt 3600 ttttgtcatt gcggatatgg tgagacaaca acgggggaga gagaaaagaa aaaaaaagaa 3660 aagaagttgc atgcattcat gcgggcccgg tacccagctt ttgttccctt tagtgagggt 3720 taattccgag cttggcgtaa tcatggtcat agctgtttcc tgtgtgaaat tgttatccgc 3780 tcacaattcc acacaacata ggagccggaa gcataaagtg taaagcctgg ggtgcctaat 3840 gagtgaggta actcacatta attgcgttgc gctcactgcc cgctttccag tcgggaaacc 3900 tgtcgtgcca gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg 3960 ggcgctcttc cgcttcctcg ctcactgact cgctgcgctc ggtcgttcgg ctgcggcgag 4020 cggtatcagc tcactcaaag gcggtaatac ggttatccac agaatcaggg gataacgcag 4080 gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa ccgtaaaaag gccgcgttgc 4140 tggcgttttt ccataggctc ggcccccctg acgagcatca caaaaatcga cgctcaagtc 4200 agaggtggcg aaacccgaca ggactataaa gataccaggc gttcccccct ggaagctccc 4260 tcgtgcgctc tcctgttccg accctgccgc ttaccggata cctgtccgcc tttctccctt 4320 cgggaagcgt ggcgctttct caatgctcac gctgtaggta tctcagttcg gtgtaggtcg 4380 ttcgctccaa gctgggctgt gtgcacgaac cccccgttca gcccgaccgc tgcgccttat 4440 ccggtaacta tcgtcttgag tccaacccgg taagacacga cttatcgcca ctggcagcag 4500 ccactggtaa caggattagc agagcgaggt atgtaggcgg tgctacagag ttcttgaagt 4560 ggtggcctaa ctacggctac actagaagga cagtatttgg tatctgcgct ctgctgaagc 4620 cagttacctt cggaaaaaga gttggtagct cttgatccgg caaacaaacc accgctggta 4680 gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag aaaaaaagga tctcaagaag 4740 atcctttgat cttttctacg gggtctgacg ctcagtggaa cgaaaactca cgttaaggga 4800 ttttggtcat gagattatca aaaaggatct tcacctagat ccttttaaat taaaaatgaa 4860 gttttaaatc aatctaaagt atatatgagt aaacttggtc tgacagttac caatgcttaa 4920 tcagtgaggc acctatctca gcgatctgtc tatttcgttc atccatagtt gcctgactgc 4980 ccgtcgtgta gataactacg atacgggagg gcttaccatc tggccccagt gctgcaatga 5040 taccgcgaga cccacgctca ccggctccag atttatcagc aataaaccag ccagccggaa 5100 gggccgagcg cagaagtggt cctgcaactt tatccgcctc catccagtct attaattgtt 5160 gccgggaagc tagagtaagt agttcgccag ttaatagttt gcgcaacgtt gttgccattg 5220 ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc ttcattcagc tccggttccc 5280 aacgatcaag gcgagttaca tgatccccca tgttgtgaaa aaaagcggtt agctccttcg 5340 gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt atcactcatg gttatggcag 5400 cactgcataa ttctcttact gtcatgccat ccgtaagatg cttttctgtg actggtgagt 5460 actcaaccaa gtcattctga gaatagtgta tgcggcgacc gagttgctct tgcccggcgt 5520 caatacggga taataccgcg ccacatagca gaactttaaa agtgctcatc attggaaaac 5580 gttcttcggg gcgaaaactc tcaaggatct taccgctgtt gagatccagt tcgatgtaac 5640 ccactcgtgc acccaactga tcttcagcat cttttacttt caccagcgtt tctgggtgag 5700 caaaaacagg aaggcaaaat gccgcaaaaa agggaataag ggcgacacgg aaatgttgaa 5760 tactcatact cttccttttt caatattatt gaagcattta tcagggttat tgtctcatga 5820 gcggatacat atttgaatgt atttagaaaa ataaacaaat aggggttccg cgcacatttc 5880 cccgaaaagt gccacctggg tccttttcat cacgtgctat aaaaataatt ataatttaaa 5940 ttttttaata taaatatata aattaaaaat agaaagtaaa aaaagaaatt aaagaaaaaa 6000 tagtttttgt tttccgaaga tgtaaaagac tctaggggga tcgccaacaa atactacctt 6060 ttatcttgct cttcctgctc tcaggtatta atgccgaatt gtttcatctt gtctgtgtag 6120 aagaccacac acgaaaatcc tgtgatttta cattttactt atcgttaatc gaatgtatat 6180 ctatttaatc tgcttttctt gtctaataaa tatatatgta aagtacgctt tttgttgaaa 6240 ttttttaaac ctttgtttat ttttttttct tcattccgta actcttctac cttctttatt 6300 tactttctaa aatccaaata caaaacataa aaataaataa acacagagta aattcccaaa 6360 ttattccatc attaaaagat acgaggcgcg tgtaagttac aggcaagcga tccgtcctaa 6420 gaaaccatta ttatcatgac attaacctat aaaaataggc gtatcacgag gccctttcgt 6480 c 6481 <210> 271 <211> 6018 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 271 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatcga ctacgtcgta aggccgtttc tgacagagta aaattcttga gggaactttc 240 accattatgg gaaatggttc aagaaggtat tgacttaaac tccatcaaat ggtcaggtca 300 ttgagtgttt tttatttgtt gtattttttt ttttttagag aaaatcctcc aatatcaaat 360 taggaatcgt agtttcatga ttttctgtta cacctaactt tttgtgtggt gccctcctcc 420 ttgtcaatat taatgttaaa gtgcaattct ttttccttat cacgttgagc cattagtatc 480 aatttgctta cctgtattcc tttactatcc tcctttttct ccttcttgat aaatgtatgt 540 agattgcgta tatagtttcg tctaccctat gaacatattc cattttgtaa tttcgtgtcg 600 tttctattat gaatttcatt tataaagttt atgtacaaat atcataaaaa aagagaatct 660 ttttaagcaa ggattttctt aacttcttcg gcgacagcat caccgacttc ggtggtactg 720 ttggaaccac ctaaatcacc agttctgata cctgcatcca aaaccttttt aactgcatct 780 tcaatggcct taccttcttc aggcaagttc aatgacaatt tcaacatcat tgcagcagac 840 aagatagtgg cgatagggtc aaccttattc tttggcaaat ctggagcaga accgtggcat 900 ggttcgtaca aaccaaatgc ggtgttcttg tctggcaaag aggccaagga cgcagatggc 960 aacaaaccca aggaacctgg gataacggag gcttcatcgg agatgatatc accaaacatg 1020 ttgctggtga ttataatacc atttaggtgg gttgggttct taactaggat catggcggca 1080 gaatcaatca attgatgttg aaccttcaat gtagggaatt cgttcttgat ggtttcctcc 1140 acagtttttc tccataatct tgaagaggcc aaaacattag ctttatccaa ggaccaaata 1200 ggcaatggtg gctcatgttg tagggccatg aaagcggcca ttcttgtgat tctttgcact 1260 tctggaacgg tgtattgttc actatcccaa gcgacaccat caccatcgtc ttcctttctc 1320 ttaccaaagt aaatacctcc cactaattct ctgacaacaa cgaagtcagt acctttagca 1380 aattgtggct tgattggaga taagtctaaa agagagtcgg atgcaaagtt acatggtctt 1440 aagttggcgt acaattgaag ttctttacgg atttttagta aaccttgttc aggtctaaca 1500 ctaccggtac cccatttagg accacccaca gcacctaaca aaacggcatc aaccttcttg 1560 gaggcttcca gcgcctcatc tggaagtggg acacctgtag catcgatagc agcaccacca 1620 attaaatgat tttcgaaatc gaacttgaca ttggaacgaa catcagaaat agctttaaga 1680 accttaatgg cttcggctgt gatttcttga ccaacgtggt cacctggcaa aacgacgatc 1740 ttcttagggg cagacatagg ggcagacatt agaatggtat atccttgaaa tatatatata 1800 tattgctgaa atgtaaaagg taagaaaagt tagaaagtaa gacgattgct aaccacctat 1860 tggaaaaaac aataggtcct taaataatat tgtcaacttc aagtattgtg atgcaagcat 1920 ttagtcatga acgcttctct attctatatg aaaagccggt tccggcctct cacctttcct 1980 ttttctccca atttttcagt tgaaaaaggt atatgcgtca ggcgacctct gaaattaaca 2040 aaaaatttcc agtcatcgaa tttgattctg tgcgatagcg cccctgtgtg ttctcgttat 2100 gttgaggaaa aaaataatgg ttgctaagag attcgaactc ttgcatctta cgatacctga 2160 gtattcccac agttaactgc ggtcaagata tttcttgaat caggcgcctt agaccgctcg 2220 gccaaacaac caattacttg ttgagaaata gagtataatt atcctataaa tataacgttt 2280 ttgaacacac atgaacaagg aagtacagga caattgattt tgaagagaat gtggattttg 2340 atgtaattgt tgggattcca tttttaataa ggcaataata ttaggtatgt ggatatacta 2400 gaagttctcc tcgagggtcg atatgcggtg tgaaataccg cacagatgcg taaggagaaa 2460 ataccgcatc aggaaattgt aaacgttaat attttgttaa aattcgcgtt aaatttttgt 2520 taaatcagct cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa 2580 gaatagaccg agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag 2640 aacgtggact ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacgt 2700 gaaccatcac cctaatcaag ttttttgggg tcgaggtgcc gtaaagcact aaatcggaac 2760 cctaaaggga gcccccgatt tagagcttga cggggaaagc cggcgaacgt ggcgagaaag 2820 gaagggaaga aagcgaaagg agcgggcgct agggcgctgg caagtgtagc ggtcacgctg 2880 cgcgtaacca ccacacccgc cgcgcttaat gcgccgctac agggcgcgtc gcgccattcg 2940 ccattcaggc tgcgcaactg ttgggaaggg cgatcggtgc gggcctcttc gctattacgc 3000 cagctggcga aggggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc 3060 cagtcacgac gttgtaaaac gacggccagt gaattgtaat acgactcact atagggcgaa 3120 ttggagctcc accgcggtgg cggccgctct agaactagtg gatcccccgg gctgcaggaa 3180 ttcgatatca agcttatcga taccgtcgac ctcgaggggg ggcccggtac ccagcttttg 3240 ttccctttag tgagggttaa ttccgagctt ggcgtaatca tggtcatagc tgtttcctgt 3300 gtgaaattgt tatccgctca caattccaca caacatagga gccggaagca taaagtgtaa 3360 agcctggggt gcctaatgag tgaggtaact cacattaatt gcgttgcgct cactgcccgc 3420 tttccagtcg ggaaacctgt cgtgccagct gcattaatga atcggccaac gcgcggggag 3480 aggcggtttg cgtattgggc gctcttccgc ttcctcgctc actgactcgc tgcgctcggt 3540 cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt tatccacaga 3600 atcaggggat aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg 3660 taaaaaggcc gcgttgctgg cgtttttcca taggctcggc ccccctgacg agcatcacaa 3720 aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga ctataaagat accaggcgtt 3780 cccccctgga agctccctcg tgcgctctcc tgttccgacc ctgccgctta ccggatacct 3840 gtccgccttt ctcccttcgg gaagcgtggc gctttctcaa tgctcacgct gtaggtatct 3900 cagttcggtg taggtcgttc gctccaagct gggctgtgtg cacgaacccc ccgttcagcc 3960 cgaccgctgc gccttatccg gtaactatcg tcttgagtcc aacccggtaa gacacgactt 4020 atcgccactg gcagcagcca ctggtaacag gattagcaga gcgaggtatg taggcggtgc 4080 tacagagttc ttgaagtggt ggcctaacta cggctacact agaaggacag tatttggtat 4140 ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa 4200 acaaaccacc gctggtagcg gtggtttttt tgtttgcaag cagcagatta cgcgcagaaa 4260 aaaaggatct caagaagatc ctttgatctt ttctacgggg tctgacgctc agtggaacga 4320 aaactcacgt taagggattt tggtcatgag attatcaaaa aggatcttca cctagatcct 4380 tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa cttggtctga 4440 cagttaccaa tgcttaatca gtgaggcacc tatctcagcg atctgtctat ttcgttcatc 4500 catagttgcc tgactgcccg tcgtgtagat aactacgata cgggagggct taccatctgg 4560 ccccagtgct gcaatgatac cgcgagaccc acgctcaccg gctccagatt tatcagcaat 4620 aaaccagcca gccggaaggg ccgagcgcag aagtggtcct gcaactttat ccgcctccat 4680 ccagtctatt aattgttgcc gggaagctag agtaagtagt tcgccagtta atagtttgcg 4740 caacgttgtt gccattgcta caggcatcgt ggtgtcacgc tcgtcgtttg gtatggcttc 4800 attcagctcc ggttcccaac gatcaaggcg agttacatga tcccccatgt tgtgaaaaaa 4860 agcggttagc tccttcggtc ctccgatcgt tgtcagaagt aagttggccg cagtgttatc 4920 actcatggtt atggcagcac tgcataattc tcttactgtc atgccatccg taagatgctt 4980 ttctgtgact ggtgagtact caaccaagtc attctgagaa tagtgtatgc ggcgaccgag 5040 ttgctcttgc ccggcgtcaa tacgggataa taccgcgcca catagcagaa ctttaaaagt 5100 gctcatcatt ggaaaacgtt cttcggggcg aaaactctca aggatcttac cgctgttgag 5160 atccagttcg atgtaaccca ctcgtgcacc caactgatct tcagcatctt ttactttcac 5220 cagcgtttct gggtgagcaa aaacaggaag gcaaaatgcc gcaaaaaagg gaataagggc 5280 gacacggaaa tgttgaatac tcatactctt cctttttcaa tattattgaa gcatttatca 5340 gggttattgt ctcatgagcg gatacatatt tgaatgtatt tagaaaaata aacaaatagg 5400 ggttccgcgc acatttcccc gaaaagtgcc acctgggtcc ttttcatcac gtgctataaa 5460 aataattata atttaaattt tttaatataa atatataaat taaaaataga aagtaaaaaa 5520 agaaattaaa gaaaaaatag tttttgtttt ccgaagatgt aaaagactct agggggatcg 5580 ccaacaaata ctacctttta tcttgctctt cctgctctca ggtattaatg ccgaattgtt 5640 tcatcttgtc tgtgtagaag accacacacg aaaatcctgt gattttacat tttacttatc 5700 gttaatcgaa tgtatatcta tttaatctgc ttttcttgtc taataaatat atatgtaaag 5760 tacgcttttt gttgaaattt tttaaacctt tgtttatttt tttttcttca ttccgtaact 5820 cttctacctt ctttatttac tttctaaaat ccaaatacaa aacataaaaa taaataaaca 5880 cagagtaaat tcccaaatta ttccatcatt aaaagatacg aggcgcgtgt aagttacagg 5940 caagcgatcc gtcctaagaa accattatta tcatgacatt aacctataaa aataggcgta 6000 tcacgaggcc ctttcgtc 6018 <210> 272 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 272 cgccgcatgc attcatgcag gcc 23 <210> 273 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 273 tgcatgaatg catgcgg 17 <210> 274 <211> 5021 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 274 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatcga ctacgtcgta aggccgtttc tgacagagta aaattcttga gggaactttc 240 accattatgg gaaatggttc aagaaggtat tgacttaaac tccatcaaat ggtcaggtca 300 ttgagtgttt tttatttgtt gtattttttt ttttttagag aaaatcctcc aatatcaaat 360 taggaatcgt agtttcatga ttttctgtta cacctaactt tttgtgtggt gccctcctcc 420 ttgtcaatat taatgttaaa gtgcaattct ttttccttat cacgttgagc cattagtatc 480 aatttgctta cctgtattcc tttactatcc tcctttttct ccttcttgat aaatgtatgt 540 agattgcgta tatagtttcg tctaccctat gaacatattc cattttgtaa tttcgtgtcg 600 tttctattat gaatttcatt tataaagttt atgtacaaat atcataaaaa aagagaatct 660 ttttaagcaa ggattttctt aacttcttcg gcgacagcat caccgacttc ggtggtactg 720 ttggaaccac ctaaatcacc agttctgata cctgcatcca aaaccttttt aactgcatct 780 tcaatggcct taccttcttc aggcaagttc aatgacaatt tcaacatcat tgcagcagac 840 aagatagtgg cgatagggtc aaccttattc tttggcaaat ctggagcaga accgtggcat 900 ggttcgtaca aaccaaatgc ggtgttcttg tctggcaaag aggccaagga cgcagatggc 960 aacaaaccca aggaacctgg gataacggag gcttcatcgg agatgatatc accaaacatg 1020 ttgctggtga ttataatacc atttaggtgg gttgggttct taactaggat catggcggca 1080 gaatcaatca attgatgttg aaccttcaat gtagggaatt cgttcttgat ggtttcctcc 1140 acagtttttc tccataatct tgaagaggcc aaaacattag ctttatccaa ggaccaaata 1200 ggcaatggtg gctcatgttg tagggccatg aaagcggcca ttcttgtgat tctttgcact 1260 tctggaacgg tgtattgttc actatcccaa gcgacaccat caccatcgtc ttcctttctc 1320 ttaccaaagt aaatacctcc cactaattct ctgacaacaa cgaagtcagt acctttagca 1380 aattgtggct tgattggaga taagtctaaa agagagtcgg atgcaaagtt acatggtctt 1440 aagttggcgt acaattgaag ttctttacgg atttttagta aaccttgttc aggtctaaca 1500 ctaccggtac cccatttagg accacccaca gcacctaaca aaacggcatc aaccttcttg 1560 gaggcttcca gcgcctcatc tggaagtggg acacctgtag catcgatagc agcaccacca 1620 attaaatgat tttcgaaatc gaacttgaca ttggaacgaa catcagaaat agctttaaga 1680 accttaatgg cttcggctgt gatttcttga ccaacgtggt cacctggcaa aacgacgatc 1740 ttcttagggg cagacatagg ggcagacatt agaatggtat atccttgaaa tatatatata 1800 tattgctgaa atgtaaaagg taagaaaagt tagaaagtaa gacgattgct aaccacctat 1860 tggaaaaaac aataggtcct taaataatat tgtcaacttc aagtattgtg atgcaagcat 1920 ttagtcatga acgcttctct attctatatg aaaagccggt tccggcctct cacctttcct 1980 ttttctccca atttttcagt tgaaaaaggt atatgcgtca ggcgacctct gaaattaaca 2040 aaaaatttcc agtcatcgaa tttgattctg tgcgatagcg cccctgtgtg ttctcgttat 2100 gttgaggaaa aaaataatgg ttgctaagag attcgaactc ttgcatctta cgatacctga 2160 gtattcccac agttaactgc ggtcaagata tttcttgaat caggcgccgc atgcattcat 2220 gcaggcccgg tacccagctt ttgttccctt tagtgagggt taattccgag cttggcgtaa 2280 tcatggtcat agctgtttcc tgtgtgaaat tgttatccgc tcacaattcc acacaacata 2340 ggagccggaa gcataaagtg taaagcctgg ggtgcctaat gagtgaggta actcacatta 2400 attgcgttgc gctcactgcc cgctttccag tcgggaaacc tgtcgtgcca gctgcattaa 2460 tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgctcttc cgcttcctcg 2520 ctcactgact cgctgcgctc ggtcgttcgg ctgcggcgag cggtatcagc tcactcaaag 2580 gcggtaatac ggttatccac agaatcaggg gataacgcag gaaagaacat gtgagcaaaa 2640 ggccagcaaa aggccaggaa ccgtaaaaag gccgcgttgc tggcgttttt ccataggctc 2700 ggcccccctg acgagcatca caaaaatcga cgctcaagtc agaggtggcg aaacccgaca 2760 ggactataaa gataccaggc gttcccccct ggaagctccc tcgtgcgctc tcctgttccg 2820 accctgccgc ttaccggata cctgtccgcc tttctccctt cgggaagcgt ggcgctttct 2880 caatgctcac gctgtaggta tctcagttcg gtgtaggtcg ttcgctccaa gctgggctgt 2940 gtgcacgaac cccccgttca gcccgaccgc tgcgccttat ccggtaacta tcgtcttgag 3000 tccaacccgg taagacacga cttatcgcca ctggcagcag ccactggtaa caggattagc 3060 agagcgaggt atgtaggcgg tgctacagag ttcttgaagt ggtggcctaa ctacggctac 3120 actagaagga cagtatttgg tatctgcgct ctgctgaagc cagttacctt cggaaaaaga 3180 gttggtagct cttgatccgg caaacaaacc accgctggta gcggtggttt ttttgtttgc 3240 aagcagcaga ttacgcgcag aaaaaaagga tctcaagaag atcctttgat cttttctacg 3300 gggtctgacg ctcagtggaa cgaaaactca cgttaaggga ttttggtcat gagattatca 3360 aaaaggatct tcacctagat ccttttaaat taaaaatgaa gttttaaatc aatctaaagt 3420 atatatgagt aaacttggtc tgacagttac caatgcttaa tcagtgaggc acctatctca 3480 gcgatctgtc tatttcgttc atccatagtt gcctgactgc ccgtcgtgta gataactacg 3540 atacgggagg gcttaccatc tggccccagt gctgcaatga taccgcgaga cccacgctca 3600 ccggctccag atttatcagc aataaaccag ccagccggaa gggccgagcg cagaagtggt 3660 cctgcaactt tatccgcctc catccagtct attaattgtt gccgggaagc tagagtaagt 3720 agttcgccag ttaatagttt gcgcaacgtt gttgccattg ctacaggcat cgtggtgtca 3780 cgctcgtcgt ttggtatggc ttcattcagc tccggttccc aacgatcaag gcgagttaca 3840 tgatccccca tgttgtgaaa aaaagcggtt agctccttcg gtcctccgat cgttgtcaga 3900 agtaagttgg ccgcagtgtt atcactcatg gttatggcag cactgcataa ttctcttact 3960 gtcatgccat ccgtaagatg cttttctgtg actggtgagt actcaaccaa gtcattctga 4020 gaatagtgta tgcggcgacc gagttgctct tgcccggcgt caatacggga taataccgcg 4080 ccacatagca gaactttaaa agtgctcatc attggaaaac gttcttcggg gcgaaaactc 4140 tcaaggatct taccgctgtt gagatccagt tcgatgtaac ccactcgtgc acccaactga 4200 tcttcagcat cttttacttt caccagcgtt tctgggtgag caaaaacagg aaggcaaaat 4260 gccgcaaaaa agggaataag ggcgacacgg aaatgttgaa tactcatact cttccttttt 4320 caatattatt gaagcattta tcagggttat tgtctcatga gcggatacat atttgaatgt 4380 atttagaaaa ataaacaaat aggggttccg cgcacatttc cccgaaaagt gccacctggg 4440 tccttttcat cacgtgctat aaaaataatt ataatttaaa ttttttaata taaatatata 4500 aattaaaaat agaaagtaaa aaaagaaatt aaagaaaaaa tagtttttgt tttccgaaga 4560 tgtaaaagac tctaggggga tcgccaacaa atactacctt ttatcttgct cttcctgctc 4620 tcaggtatta atgccgaatt gtttcatctt gtctgtgtag aagaccacac acgaaaatcc 4680 tgtgatttta cattttactt atcgttaatc gaatgtatat ctatttaatc tgcttttctt 4740 gtctaataaa tatatatgta aagtacgctt tttgttgaaa ttttttaaac ctttgtttat 4800 ttttttttct tcattccgta actcttctac cttctttatt tactttctaa aatccaaata 4860 caaaacataa aaataaataa acacagagta aattcccaaa ttattccatc attaaaagat 4920 acgaggcgcg tgtaagttac aggcaagcga tccgtcctaa gaaaccatta ttatcatgac 4980 attaacctat aaaaataggc gtatcacgag gccctttcgt c 5021 <210> 275 <211> 6408 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 275 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatcga ctacgtcgta aggccgtttc tgacagagta aaattcttga gggaactttc 240 accattatgg gaaatggttc aagaaggtat tgacttaaac tccatcaaat ggtcaggtca 300 ttgagtgttt tttatttgtt gtattttttt ttttttagag aaaatcctcc aatatcaaat 360 taggaatcgt agtttcatga ttttctgtta cacctaactt tttgtgtggt gccctcctcc 420 ttgtcaatat taatgttaaa gtgcaattct ttttccttat cacgttgagc cattagtatc 480 aatttgctta cctgtattcc tttactatcc tcctttttct ccttcttgat aaatgtatgt 540 agattgcgta tatagtttcg tctaccctat gaacatattc cattttgtaa tttcgtgtcg 600 tttctattat gaatttcatt tataaagttt atgtacaaat atcataaaaa aagagaatct 660 ttttaagcaa ggattttctt aacttcttcg gcgacagcat caccgacttc ggtggtactg 720 ttggaaccac ctaaatcacc agttctgata cctgcatcca aaaccttttt aactgcatct 780 tcaatggcct taccttcttc aggcaagttc aatgacaatt tcaacatcat tgcagcagac 840 aagatagtgg cgatagggtc aaccttattc tttggcaaat ctggagcaga accgtggcat 900 ggttcgtaca aaccaaatgc ggtgttcttg tctggcaaag aggccaagga cgcagatggc 960 aacaaaccca aggaacctgg gataacggag gcttcatcgg agatgatatc accaaacatg 1020 ttgctggtga ttataatacc atttaggtgg gttgggttct taactaggat catggcggca 1080 gaatcaatca attgatgttg aaccttcaat gtagggaatt cgttcttgat ggtttcctcc 1140 acagtttttc tccataatct tgaagaggcc aaaacattag ctttatccaa ggaccaaata 1200 ggcaatggtg gctcatgttg tagggccatg aaagcggcca ttcttgtgat tctttgcact 1260 tctggaacgg tgtattgttc actatcccaa gcgacaccat caccatcgtc ttcctttctc 1320 ttaccaaagt aaatacctcc cactaattct ctgacaacaa cgaagtcagt acctttagca 1380 aattgtggct tgattggaga taagtctaaa agagagtcgg atgcaaagtt acatggtctt 1440 aagttggcgt acaattgaag ttctttacgg atttttagta aaccttgttc aggtctaaca 1500 ctaccggtac cccatttagg accacccaca gcacctaaca aaacggcatc aaccttcttg 1560 gaggcttcca gcgcctcatc tggaagtggg acacctgtag catcgatagc agcaccacca 1620 attaaatgat tttcgaaatc gaacttgaca ttggaacgaa catcagaaat agctttaaga 1680 accttaatgg cttcggctgt gatttcttga ccaacgtggt cacctggcaa aacgacgatc 1740 ttcttagggg cagacatagg ggcagacatt agaatggtat atccttgaaa tatatatata 1800 tattgctgaa atgtaaaagg taagaaaagt tagaaagtaa gacgattgct aaccacctat 1860 tggaaaaaac aataggtcct taaataatat tgtcaacttc aagtattgtg atgcaagcat 1920 ttagtcatga acgcttctct attctatatg aaaagccggt tccggcctct cacctttcct 1980 ttttctccca atttttcagt tgaaaaaggt atatgcgtca ggcgacctct gaaattaaca 2040 aaaaatttcc agtcatcgaa tttgattctg tgcgatagcg cccctgtgtg ttctcgttat 2100 gttgaggaaa aaaataatgg ttgctaagag attcgaactc ttgcatctta cgatacctga 2160 gtattcccac agttaactgc ggtcaagata tttcttgaat caggcgccgc atgccggtag 2220 aggtgtggtc aataagagcg acctcatgct atacctgaga aagcaacctg acctacagga 2280 aagagttact caagaataag aattttcgtt ttaaaaccta agagtcactt taaaatttgt 2340 atacacttat tttttttata acttatttaa taataaaaat cataaatcat aagaaattcg 2400 cttatttaga agtgtcaaca acgtatctac caacgatttg acccttttcc atcttttcgt 2460 aaatttctgg caaggtagac aagccgacaa ccttgattgg agacttgacc aaacctctgg 2520 cgaagaagtc caaagcttct gaataagccc tcgtaatata ttttcatgaa gaatttaggt 2580 ccaaaaaaaa gatgggcatt aattctagtc atttaaaaaa ttctatagat cagaggttac 2640 atggccaaga ttgaaactta gaggagtata gttacataaa agaaggcaaa acgatgtata 2700 aatgaaagaa attgagatgg tgcacgatgc acagttgaag tgaacttgcg gggtttttca 2760 gtatctacga ttcatagatc tggaattggg ccggcctggc cactagtcat catgatatcc 2820 tcgagggccg cctgggcctg tcgagagatc tctttttttg ggtttggtgg ggtatcttca 2880 tcatcgaata gatagttata tacatcatcc attgtagtgg tattaaacat ccctgtagtg 2940 attccaaacg cgttatacgc agtttggtcc gtccaaccag gtgacagtgg ttttgaatta 3000 ttaccatcat caattttact agccgtgatt tcattattca tgaagttatc atgaacgtta 3060 gaggaggcaa ttggttgtga aagcgcttga gaatttgttt gagttgttat gaggttcgga 3120 ccgttgctac tgttagtgaa agtgaaggac aatgagctat cagcaatatt cccactttga 3180 ttaaaattgg cggcggtacc caattcgacc tttctcttct tttttggagg ctcgggaatt 3240 aattccgctt tatccatctt tgcagcggcc gcttgcaaaa gcctaggcct ccaaaaaagc 3300 ctcctcacta cttctggaat agctcagagg cagaggcggc ctcggcctct gcataaataa 3360 aaaaaattag tcagccatgg ggcggagaat gggcggaact gggcggagtt aggggcggga 3420 tgggcggagt taggggcggg actatggttg ctgactaatt gagatgcatg ctttgcatac 3480 ttctgcctgc tggggagcct ggggactttc cacacctggt tgctgactaa ttgagatgca 3540 tgctttgcat acttctgcct gctggggagc ctggggactt tccacaccct aactgacaca 3600 cattccacag ggcccggtac ccagcttttg ttccctttag tgagggttaa ttccgagctt 3660 ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca caattccaca 3720 caacatagga gccggaagca taaagtgtaa agcctggggt gcctaatgag tgaggtaact 3780 cacattaatt gcgttgcgct cactgcccgc tttccagtcg ggaaacctgt cgtgccagct 3840 gcattaatga atcggccaac gcgcggggag aggcggtttg cgtattgggc gctcttccgc 3900 ttcctcgctc actgactcgc tgcgctcggt cgttcggctg cggcgagcgg tatcagctca 3960 ctcaaaggcg gtaatacggt tatccacaga atcaggggat aacgcaggaa agaacatgtg 4020 agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca 4080 taggctcggc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa 4140 cccgacagga ctataaagat accaggcgtt cccccctgga agctccctcg tgcgctctcc 4200 tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg gaagcgtggc 4260 gctttctcaa tgctcacgct gtaggtatct cagttcggtg taggtcgttc gctccaagct 4320 gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg gtaactatcg 4380 tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca ctggtaacag 4440 gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt ggcctaacta 4500 cggctacact agaaggacag tatttggtat ctgcgctctg ctgaagccag ttaccttcgg 4560 aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg gtggtttttt 4620 tgtttgcaag cagcagatta cgcgcagaaa aaaaggatct caagaagatc ctttgatctt 4680 ttctacgggg tctgacgctc agtggaacga aaactcacgt taagggattt tggtcatgag 4740 attatcaaaa aggatcttca cctagatcct tttaaattaa aaatgaagtt ttaaatcaat 4800 ctaaagtata tatgagtaaa cttggtctga cagttaccaa tgcttaatca gtgaggcacc 4860 tatctcagcg atctgtctat ttcgttcatc catagttgcc tgactgcccg tcgtgtagat 4920 aactacgata cgggagggct taccatctgg ccccagtgct gcaatgatac cgcgagaccc 4980 acgctcaccg gctccagatt tatcagcaat aaaccagcca gccggaaggg ccgagcgcag 5040 aagtggtcct gcaactttat ccgcctccat ccagtctatt aattgttgcc gggaagctag 5100 agtaagtagt tcgccagtta atagtttgcg caacgttgtt gccattgcta caggcatcgt 5160 ggtgtcacgc tcgtcgtttg gtatggcttc attcagctcc ggttcccaac gatcaaggcg 5220 agttacatga tcccccatgt tgtgaaaaaa agcggttagc tccttcggtc ctccgatcgt 5280 tgtcagaagt aagttggccg cagtgttatc actcatggtt atggcagcac tgcataattc 5340 tcttactgtc atgccatccg taagatgctt ttctgtgact ggtgagtact caaccaagtc 5400 attctgagaa tagtgtatgc ggcgaccgag ttgctcttgc ccggcgtcaa tacgggataa 5460 taccgcgcca catagcagaa ctttaaaagt gctcatcatt ggaaaacgtt cttcggggcg 5520 aaaactctca aggatcttac cgctgttgag atccagttcg atgtaaccca ctcgtgcacc 5580 caactgatct tcagcatctt ttactttcac cagcgtttct gggtgagcaa aaacaggaag 5640 gcaaaatgcc gcaaaaaagg gaataagggc gacacggaaa tgttgaatac tcatactctt 5700 cctttttcaa tattattgaa gcatttatca gggttattgt ctcatgagcg gatacatatt 5760 tgaatgtatt tagaaaaata aacaaatagg ggttccgcgc acatttcccc gaaaagtgcc 5820 acctgggtcc ttttcatcac gtgctataaa aataattata atttaaattt tttaatataa 5880 atatataaat taaaaataga aagtaaaaaa agaaattaaa gaaaaaatag tttttgtttt 5940 ccgaagatgt aaaagactct agggggatcg ccaacaaata ctacctttta tcttgctctt 6000 cctgctctca ggtattaatg ccgaattgtt tcatcttgtc tgtgtagaag accacacacg 6060 aaaatcctgt gattttacat tttacttatc gttaatcgaa tgtatatcta tttaatctgc 6120 ttttcttgtc taataaatat atatgtaaag tacgcttttt gttgaaattt tttaaacctt 6180 tgtttatttt tttttcttca ttccgtaact cttctacctt ctttatttac tttctaaaat 6240 ccaaatacaa aacataaaaa taaataaaca cagagtaaat tcccaaatta ttccatcatt 6300 aaaagatacg aggcgcgtgt aagttacagg caagcgatcc gtcctaagaa accattatta 6360 tcatgacatt aacctataaa aataggcgta tcacgaggcc ctttcgtc 6408 <210> 276 <211> 6308 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 276 tcgcgcgttt cggtgatgac ggtgaaaacc tctgacacat gcagctcccg gagacggtca 60 cagcttgtct gtaagcggat gccgggagca gacaagcccg tcagggcgcg tcagcgggtg 120 ttggcgggtg tcggggctgg cttaactatg cggcatcaga gcagattgta ctgagagtgc 180 accatatcga ctacgtcgta aggccgtttc tgacagagta aaattcttga gggaactttc 240 accattatgg gaaatggttc aagaaggtat tgacttaaac tccatcaaat ggtcaggtca 300 ttgagtgttt tttatttgtt gtattttttt ttttttagag aaaatcctcc aatatcaaat 360 taggaatcgt agtttcatga ttttctgtta cacctaactt tttgtgtggt gccctcctcc 420 ttgtcaatat taatgttaaa gtgcaattct ttttccttat cacgttgagc cattagtatc 480 aatttgctta cctgtattcc tttactatcc tcctttttct ccttcttgat aaatgtatgt 540 agattgcgta tatagtttcg tctaccctat gaacatattc cattttgtaa tttcgtgtcg 600 tttctattat gaatttcatt tataaagttt atgtacaaat atcataaaaa aagagaatct 660 ttttaagcaa ggattttctt aacttcttcg gcgacagcat caccgacttc ggtggtactg 720 ttggaaccac ctaaatcacc agttctgata cctgcatcca aaaccttttt aactgcatct 780 tcaatggcct taccttcttc aggcaagttc aatgacaatt tcaacatcat tgcagcagac 840 aagatagtgg cgatagggtc aaccttattc tttggcaaat ctggagcaga accgtggcat 900 ggttcgtaca aaccaaatgc ggtgttcttg tctggcaaag aggccaagga cgcagatggc 960 aacaaaccca aggaacctgg gataacggag gcttcatcgg agatgatatc accaaacatg 1020 ttgctggtga ttataatacc atttaggtgg gttgggttct taactaggat catggcggca 1080 gaatcaatca attgatgttg aaccttcaat gtagggaatt cgttcttgat ggtttcctcc 1140 acagtttttc tccataatct tgaagaggcc aaaacattag ctttatccaa ggaccaaata 1200 ggcaatggtg gctcatgttg tagggccatg aaagcggcca ttcttgtgat tctttgcact 1260 tctggaacgg tgtattgttc actatcccaa gcgacaccat caccatcgtc ttcctttctc 1320 ttaccaaagt aaatacctcc cactaattct ctgacaacaa cgaagtcagt acctttagca 1380 aattgtggct tgattggaga taagtctaaa agagagtcgg atgcaaagtt acatggtctt 1440 aagttggcgt acaattgaag ttctttacgg atttttagta aaccttgttc aggtctaaca 1500 ctaccggtac cccatttagg accacccaca gcacctaaca aaacggcatc aaccttcttg 1560 gaggcttcca gcgcctcatc tggaagtggg acacctgtag catcgatagc agcaccacca 1620 attaaatgat tttcgaaatc gaacttgaca ttggaacgaa catcagaaat agctttaaga 1680 accttaatgg cttcggctgt gatttcttga ccaacgtggt cacctggcaa aacgacgatc 1740 ttcttagggg cagacatagg ggcagacatt agaatggtat atccttgaaa tatatatata 1800 tattgctgaa atgtaaaagg taagaaaagt tagaaagtaa gacgattgct aaccacctat 1860 tggaaaaaac aataggtcct taaataatat tgtcaacttc aagtattgtg atgcaagcat 1920 ttagtcatga acgcttctct attctatatg aaaagccggt tccggcctct cacctttcct 1980 ttttctccca atttttcagt tgaaaaaggt atatgcgtca ggcgacctct gaaattaaca 2040 aaaaatttcc agtcatcgaa tttgattctg tgcgatagcg cccctgtgtg ttctcgttat 2100 gttgaggaaa aaaataatgg ttgctaagag attcgaactc ttgcatctta cgatacctga 2160 gtattcccac agttaactgc ggtcaagata tttcttgaat caggcgccgc atgccggtag 2220 aggtgtggtc aataagagcg acctcatgct atacctgaga aagcaacctg acctacagga 2280 aagagttact caagaataag aattttcgtt ttaaaaccta agagtcactt taaaatttgt 2340 atacacttat tttttttata acttatttaa taataaaaat cataaatcat aagaaattcg 2400 cttatttaga agtgtcaaca acgtatctac caacgatttg acccttttcc atcttttcgt 2460 aaatttctgg caaggtagac aagccgacaa ccttgattgg agacttgacc aaacctctgg 2520 cgaagaagtc caaagcttct gaataagccc tcgtaatata ttttcatgaa gaatttaggt 2580 ccaaaaaaaa gatgggcatt aattctagtc atttaaaaaa ttctatagat cagaggttac 2640 atggccaaga ttgaaactta gaggagtata gttacataaa agaaggcaaa acgatgtata 2700 aatgaaagaa attgagatgg tgcacgatgc acagttgaag tgaacttgcg gggtttttca 2760 gtatctacga ttcatagatc tggaattggg ccggcctggc cactagtcat catgatatcc 2820 tcgagggccg cctgggcctg tcgagagatc tctttttttg ggtttggtgg ggtatcttca 2880 tcatcgaata gatagttata tacatcatcc attgtagtgg tattaaacat ccctgtagtg 2940 attccaaacg cgttatacgc agtttggtcc gtccaaccag gtgacagtgg ttttgaatta 3000 ttaccatcat caattttact agccgtgatt tcattattca tgaagttatc atgaacgtta 3060 gaggaggcaa ttggttgtga aagcgcttga gaatttgttt gagttgttat gaggttcgga 3120 ccgttgctac tgttagtgaa agtgaaggac aatgagctat cagcaatatt cccactttga 3180 ttaaaattgg cggcggtacc caattcgacc tttctcttct tttttggagg ctcgggaatt 3240 aattccgctt tatccatctt tgcagcggcc gcagccatgg ggcggagaat gggcggaact 3300 gggcggagtt aggggcggga tgggcggagt taggggcggg actatggttg ctgactaatt 3360 gagatgcatg ctttgcatac ttctgcctgc tggggagcct ggggactttc cacacctggt 3420 tgctgactaa ttgagatgca tgctttgcat acttctgcct gctggggagc ctggggactt 3480 tccacaccct aactgacaca cattccacag ggcccggtac ccagcttttg ttccctttag 3540 tgagggttaa ttccgagctt ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt 3600 tatccgctca caattccaca caacatagga gccggaagca taaagtgtaa agcctggggt 3660 gcctaatgag tgaggtaact cacattaatt gcgttgcgct cactgcccgc tttccagtcg 3720 ggaaacctgt cgtgccagct gcattaatga atcggccaac gcgcggggag aggcggtttg 3780 cgtattgggc gctcttccgc ttcctcgctc actgactcgc tgcgctcggt cgttcggctg 3840 cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt tatccacaga atcaggggat 3900 aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc 3960 gcgttgctgg cgtttttcca taggctcggc ccccctgacg agcatcacaa aaatcgacgc 4020 tcaagtcaga ggtggcgaaa cccgacagga ctataaagat accaggcgtt cccccctgga 4080 agctccctcg tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt 4140 ctcccttcgg gaagcgtggc gctttctcaa tgctcacgct gtaggtatct cagttcggtg 4200 taggtcgttc gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc 4260 gccttatccg gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg 4320 gcagcagcca ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc 4380 ttgaagtggt ggcctaacta cggctacact agaaggacag tatttggtat ctgcgctctg 4440 ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc 4500 gctggtagcg gtggtttttt tgtttgcaag cagcagatta cgcgcagaaa aaaaggatct 4560 caagaagatc ctttgatctt ttctacgggg tctgacgctc agtggaacga aaactcacgt 4620 taagggattt tggtcatgag attatcaaaa aggatcttca cctagatcct tttaaattaa 4680 aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa cttggtctga cagttaccaa 4740 tgcttaatca gtgaggcacc tatctcagcg atctgtctat ttcgttcatc catagttgcc 4800 tgactgcccg tcgtgtagat aactacgata cgggagggct taccatctgg ccccagtgct 4860 gcaatgatac cgcgagaccc acgctcaccg gctccagatt tatcagcaat aaaccagcca 4920 gccggaaggg ccgagcgcag aagtggtcct gcaactttat ccgcctccat ccagtctatt 4980 aattgttgcc gggaagctag agtaagtagt tcgccagtta atagtttgcg caacgttgtt 5040 gccattgcta caggcatcgt ggtgtcacgc tcgtcgtttg gtatggcttc attcagctcc 5100 ggttcccaac gatcaaggcg agttacatga tcccccatgt tgtgaaaaaa agcggttagc 5160 tccttcggtc ctccgatcgt tgtcagaagt aagttggccg cagtgttatc actcatggtt 5220 atggcagcac tgcataattc tcttactgtc atgccatccg taagatgctt ttctgtgact 5280 ggtgagtact caaccaagtc attctgagaa tagtgtatgc ggcgaccgag ttgctcttgc 5340 ccggcgtcaa tacgggataa taccgcgcca catagcagaa ctttaaaagt gctcatcatt 5400 ggaaaacgtt cttcggggcg aaaactctca aggatcttac cgctgttgag atccagttcg 5460 atgtaaccca ctcgtgcacc caactgatct tcagcatctt ttactttcac cagcgtttct 5520 gggtgagcaa aaacaggaag gcaaaatgcc gcaaaaaagg gaataagggc gacacggaaa 5580 tgttgaatac tcatactctt cctttttcaa tattattgaa gcatttatca gggttattgt 5640 ctcatgagcg gatacatatt tgaatgtatt tagaaaaata aacaaatagg ggttccgcgc 5700 acatttcccc gaaaagtgcc acctgggtcc ttttcatcac gtgctataaa aataattata 5760 atttaaattt tttaatataa atatataaat taaaaataga aagtaaaaaa agaaattaaa 5820 gaaaaaatag tttttgtttt ccgaagatgt aaaagactct agggggatcg ccaacaaata 5880 ctacctttta tcttgctctt cctgctctca ggtattaatg ccgaattgtt tcatcttgtc 5940 tgtgtagaag accacacacg aaaatcctgt gattttacat tttacttatc gttaatcgaa 6000 tgtatatcta tttaatctgc ttttcttgtc taataaatat atatgtaaag tacgcttttt 6060 gttgaaattt tttaaacctt tgtttatttt tttttcttca ttccgtaact cttctacctt 6120 ctttatttac tttctaaaat ccaaatacaa aacataaaaa taaataaaca cagagtaaat 6180 tcccaaatta ttccatcatt aaaagatacg aggcgcgtgt aagttacagg caagcgatcc 6240 gtcctaagaa accattatta tcatgacatt aacctataaa aataggcgta tcacgaggcc 6300 ctttcgtc 6308 <210> 277 <211> 8068 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (1062) <223> n is a, c, g, or t <400> 277 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgtttcgaag 240 atatcgttga cattgattat tgtctagtta ttaatagtaa tcaattacgg ggtcattagt 300 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 360 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 420 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 480 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 540 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 600 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 660 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 720 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 780 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcactt aagctggagc 840 tttgggagga gacggggagg acagactgga ggcgtgggcc cactagtgtt tagtgaaccg 900 tcagatcgcc tggagacgcc atccacgctg ttttgacctc catagaagac accgggaccg 960 atccagcctc cggactctag cctcgagccc aagcttggta ccgagctcgg atccagccac 1020 catgggagtc aaagttctgt ttgccctgat ctgcatcgct gnggccgagg ccaagcccac 1080 cgagaacaac gaagacttca acatcgtggc cgtggccagc aacttcgcga ccacggatct 1140 cgatgctgac cgcgggaagt tgcccggcaa gaagctgccg ctggaggtgc tcaaagagct 1200 ggaagccaat gcccggaaag ctggctgcac caggggctgt ctgatctgcc tgtcccacat 1260 caagtgcacg cccaagatga agaagttcat cccaggacgc tgccacacct acgaaggcga 1320 caaagagtcc gcacagggcg gcataggcga ggcgatcgtc gacattcctg agattcctgg 1380 gttcaaggac ttggagcccc tggagcagtt catcgcacag gtcgatctgt gtgtggactg 1440 cacaactggc tgcctcaaag ggcttgccaa cgtgcagtgt tctgacctgc tcaagaagtg 1500 gctgccgcaa cgctgtgcga cctttgccag caagatccag ggccaggtgg acaagatcaa 1560 gggggccggt ggtgactaag cggccgcttc gagcagacat gataagatac attgatgagt 1620 ttggacaaac cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg 1680 ctattgcttt atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca 1740 ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc 1800 tctacaaatg tggtacaacc ggtctagtta ttaatagtaa tcaattacgg ggtcattagt 1860 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 1920 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 1980 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 2040 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 2100 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 2160 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 2220 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 2280 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 2340 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctctctggct 2400 aactagagaa cccactgctt actggcttat cgaaatttta attaacgttg gcaccatgct 2460 gctgctgctg ctgctgctgg gcctgaggct acagctctcc ctgggcatca tcccagttga 2520 ggaggagaac ccggacttct ggaaccgcga ggcagccgag gccctgggtg ccgccaagaa 2580 gctgcagcct gcacagacag ccgccaagaa cctcatcatc ttcctgggcg atgggatggg 2640 ggtgtctacg gtgacagctg ccaggatcct aaaagggcag aagaaggaca aactggggcc 2700 tgagataccc ctggccatgg accgcttccc atatgtggct ctgtccaaga catacaatgt 2760 agacaaacat gtgccagaca gtggagccac agccacggcc tacctgtgcg gggtcaaggg 2820 caacttccag accattggct tgagtgcagc cgcccgcttt aaccagtgca acacgacacg 2880 cggcaacgag gtcatctccg tgatgaatcg ggccaagaaa gcagggaagt cagtgggagt 2940 ggtaaccacc acacgagtgc agcacgcctc gccagccggc acctacgccc acacggtgaa 3000 ccgcaactgg tactcggacg ccgacgtgcc tgcctcggcc cgccaggagg ggtgccagga 3060 catcgctacg cagctcatct ccaacatgga cattgacgtg atcctaggtg gaggccgaaa 3120 gtacatgttt cgcatgggaa ccccagaccc tgagtaccca gatgactaca gccaaggtgg 3180 gaccaggctg gacgggaaga atctggtgca ggaatggctg gcgaagcgcc agggtgcccg 3240 gtatgtgtgg aaccgcactg agctcatgca ggcttccctg gacccgtctg tgacccatct 3300 catgggtctc tttgagcctg gagacatgaa atacgagatc caccgagact ccacactgga 3360 cccctccctg atggagatga cagaggctgc cctgcgcctg ctgagcagga acccccgcgg 3420 cttcttcctc ttcgtggagg gtggtcgcat cgaccatggt catcatgaaa gcagggctta 3480 ccgggcactg actgagacga tcatgttcga cgacgccatt gagagggcgg gccagctcac 3540 cagcgaggag gacacgctga gcctcgtcac tgccgaccac tcccacgtct tctccttcgg 3600 aggctacccc ctgcgaggga gctccatctt cgggctggcc cctggcaagg cccgggacag 3660 gaaggcctac acggtcctcc tatacggaaa cggtccaggc tatgtgctca aggacggcgc 3720 ccggccggat gttaccgaga gcgagagcgg gagccccgag tatcggcagc agtcagcagt 3780 gcccctggac gaagagaccc acgcaggcga ggacgtggcg gtgttcgcgc gcggcccgca 3840 ggcgcacctg gttcacggcg tgcaggagca gaccttcata gcgcacgtca tggccttcgc 3900 cgcctgcctg gagccctaca ccgcctgcga cctggcgccc cccgccggca ccaccgacgc 3960 cgcgcacccg ggttactcta gagtcggggc ggccggctag gtttaaaccc gctgatcagc 4020 ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 4080 gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 4140 ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 4200 ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg cttctgaggc 4260 ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg gcgcattaag 4320 cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg ccctagcgcc 4380 cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc cccgtcaagc 4440 tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc tcgaccccaa 4500 aaaacttgat tagggtgatg gttcacgtac ctagaagttc ctattccgaa gttcctattc 4560 tctagaaagt ataggaactt ccttggccaa aaagcctgaa ctcaccgcga cgtctgtcga 4620 gaagtttctg atcgaaaagt tcgacagcgt ctccgacctg atgcagctct cggagggcga 4680 agaatctcgt gctttcagct tcgatgtagg agggcgtgga tatgtcctgc gggtaaatag 4740 ctgcgccgat ggtttctaca aagatcgtta tgtttatcgg cactttgcat cggccgcgct 4800 cccgattccg gaagtgcttg acattgggga attcagcgag agcctgacct attgcatctc 4860 ccgccgtgca cagggtgtca cgttgcaaga cctgcctgaa accgaactgc ccgctgttct 4920 gcagccggtc gcggaggcca tggatgcgat cgctgcggcc gatcttagcc agacgagcgg 4980 gttcggccca ttcggaccgc aaggaatcgg tcaatacact acatggcgtg atttcatatg 5040 cgcgattgct gatccccatg tgtatcactg gcaaactgtg atggacgaca ccgtcagtgc 5100 gtccgtcgcg caggctctcg atgagctgat gctttgggcc gaggactgcc ccgaagtccg 5160 gcacctcgtg cacgcggatt tcggctccaa caatgtcctg acggacaatg gccgcataac 5220 agcggtcatt gactggagcg aggcgatgtt cggggattcc caatacgagg tcgccaacat 5280 cttcttctgg aggccgtggt tggcttgtat ggagcagcag acgcgctact tcgagcggag 5340 gcatccggag cttgcaggat cgccgcggct ccgggcgtat atgctccgca ttggtcttga 5400 ccaactctat cagagcttgg ttgacggcaa tttcgatgat gcagcttggg cgcagggtcg 5460 atgcgacgca atcgtccgat ccggagccgg gactgtcggg cgtacacaaa tcgcccgcag 5520 aagcgcggcc gtctggaccg atggctgtgt agaagtactc gccgatagtg gaaaccgacg 5580 ccccagcact cgtccgaggg caaaggaata gcacgtacta cgagatttcg attccaccgc 5640 cgccttctat gaaaggttgg gcttcggaat cgttttccgg gacgccggct ggatgatcct 5700 ccagcgcggg gatctcatgc tggagttctt cgcccacccc aacttgttta ttgcagctta 5760 taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 5820 gcattctagt tgtggtttgt ccaaactcat caatgtatct tatcatgtct gtataccgtc 5880 gacctctagc tagagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 5940 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 6000 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 6060 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 6120 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 6180 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 6240 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 6300 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 6360 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 6420 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 6480 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 6540 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 6600 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 6660 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 6720 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 6780 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 6840 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 6900 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 6960 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 7020 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 7080 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 7140 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 7200 aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 7260 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 7320 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 7380 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 7440 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 7500 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 7560 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 7620 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 7680 ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 7740 aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 7800 gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 7860 gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 7920 ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 7980 catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 8040 atttccccga aaagtgccac ctgacgtc 8068 <210> 278 <211> 6083 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 278 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240 gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300 tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360 cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420 attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480 atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540 atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600 tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660 actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720 aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780 gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840 ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900 gtttaaacgg gccctctaga gatatcatgg atgctaagtc cctgacagcg tggagccgca 960 cactggttac cttcaaagat gttttcgtgg atttcacccg cgaagagtgg aaactgctgg 1020 ataccgcaca gcagattgtg tatcgcaacg ttatgctgga aaactacaag aatctggtta 1080 gcctgggcta tcagctgaca aaacccgacg tcatcctgcg tctggaaaag ggtgaagagc 1140 cgtggctggt tgaacgggag attcaccagg agacacatcc tgattctgaa actgcctttg 1200 agatcaaaag ctccgtcagt ccgaaaaaga aacgtaaagt ggggctcgag cccggggaaa 1260 agccatataa atgccccgag tgcggcaaat cattcagcca aagtagcaac ttagtaagac 1320 accagcgcac ccataccggg gaaaagccat ataaatgccc cgagtgcggc aaatcattca 1380 gccaaagtag caacttagta agacaccagc gcacccatac cggggaaaag ccatataaat 1440 gccccgagtg cggcaaatca ttcagccaaa gtagcaactt agtaagacac cagcgcaccc 1500 ataccggtga gcagaaactc atctctgaag aagatctgga acaaaagttg atttcagaag 1560 aagatctgga acagaagctc atctctgagg aagatctgta agcggccgcg aattccacca 1620 cactggacta gtggatccga gctcggtacc aagcttaagt ttaaaccgct gatcagcctc 1680 gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc cttccttgac 1740 cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg catcgcattg 1800 tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca agggggagga 1860 ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggctt ctgaggcgga 1920 aagaaccagc tggggctcta gggggtatcc ccacgcgccc tgtagcggcg cattaagcgc 1980 ggcgggtgtg gtggttacgc gcagcgtgac cgctacactt gccagcgccc tagcgcccgc 2040 tcctttcgct ttcttccctt cctttctcgc cacgttcgcc ggctttcccc gtcaagctct 2100 aaatcggggg ctccctttag ggttccgatt tagtgcttta cggcacctcg accccaaaaa 2160 acttgattag ggtgatggtt cacgtagtgg gccatcgccc tgatagacgg tttttcgccc 2220 tttgacgttg gagtccacgt tctttaatag tggactcttg ttccaaactg gaacaacact 2280 caaccctatc tcggtctatt cttttgattt ataagggatt ttgccgattt cggcctattg 2340 gttaaaaaat gagctgattt aacaaaaatt taacgcgaat taattctgtg gaatgtgtgt 2400 cagttagggt gtggaaagtc cccaggctcc ccagcaggca gaagtatgca aagcatgcat 2460 ctcaattagt cagcaaccag gtgtggaaag tccccaggct ccccagcagg cagaagtatg 2520 caaagcatgc atctcaatta gtcagcaacc atagtcccgc ccctaactcc gcccatcccg 2580 cccctaactc cgcccagttc cgcccattct ccgccccatg gctgactaat tttttttatt 2640 tatgcagagg ccgaggccgc ctctgcctct gagctattcc agaagtagtg aggaggcttt 2700 tttggaggcc taggcttttg caaaaagctc ccgggagctt gtatatccat tttcggatct 2760 gatcaagaga caggatgagg atcgtttcgc atgattgaac aagatggatt gcacgcaggt 2820 tctccggccg cttgggtgga gaggctattc ggctatgact gggcacaaca gacaatcggc 2880 tgctctgatg ccgccgtgtt ccggctgtca gcgcaggggc gcccggttct ttttgtcaag 2940 accgacctgt ccggtgccct gaatgaactg caggacgagg cagcgcggct atcgtggctg 3000 gccacgacgg gcgttccttg cgcagctgtg ctcgacgttg tcactgaagc gggaagggac 3060 tggctgctat tgggcgaagt gccggggcag gatctcctgt catctcacct tgctcctgcc 3120 gagaaagtat ccatcatggc tgatgcaatg cggcggctgc atacgcttga tccggctacc 3180 tgcccattcg accaccaagc gaaacatcgc atcgagcgag cacgtactcg gatggaagcc 3240 ggtcttgtcg atcaggatga tctggacgaa gagcatcagg ggctcgcgcc agccgaactg 3300 ttcgccaggc tcaaggcgcg catgcccgac ggcgaggatc tcgtcgtgac ccatggcgat 3360 gcctgcttgc cgaatatcat ggtggaaaat ggccgctttt ctggattcat cgactgtggc 3420 cggctgggtg tggcggaccg ctatcaggac atagcgttgg ctacccgtga tattgctgaa 3480 gagcttggcg gcgaatgggc tgaccgcttc ctcgtgcttt acggtatcgc cgctcccgat 3540 tcgcagcgca tcgccttcta tcgccttctt gacgagttct tctgagcggg actctggggt 3600 tcgaaatgac cgaccaagcg acgcccaacc tgccatcacg agatttcgat tccaccgccg 3660 ccttctatga aaggttgggc ttcggaatcg ttttccggga cgccggctgg atgatcctcc 3720 agcgcgggga tctcatgctg gagttcttcg cccaccccaa cttgtttatt gcagcttata 3780 atggttacaa ataaagcaat agcatcacaa atttcacaaa taaagcattt ttttcactgc 3840 attctagttg tggtttgtcc aaactcatca atgtatctta tcatgtctgt ataccgtcga 3900 cctctagcta gagcttggcg taatcatggt catagctgtt tcctgtgtga aattgttatc 3960 cgctcacaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc tggggtgcct 4020 aatgagtgag ctaactcaca ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa 4080 acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta 4140 ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc 4200 gagcggtatc agctcactca aaggcggtaa tacggttatc cacagaatca ggggataacg 4260 caggaaagaa catgtgagca aaaggccagc aaaaggccag gaaccgtaaa aaggccgcgt 4320 tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat cgacgctcaa 4380 gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc cctggaagct 4440 ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc 4500 cttcgggaag cgtggcgctt tctcatagct cacgctgtag gtatctcagt tcggtgtagg 4560 tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct 4620 tatccggtaa ctatcgtctt gagtccaacc cggtaagaca cgacttatcg ccactggcag 4680 cagccactgg taacaggatt agcagagcga ggtatgtagg cggtgctaca gagttcttga 4740 agtggtggcc taactacggc tacactagaa gaacagtatt tggtatctgc gctctgctga 4800 agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa accaccgctg 4860 gtagcggttt ttttgtttgc aagcagcaga ttacgcgcag aaaaaaagga tctcaagaag 4920 atcctttgat cttttctacg gggtctgacg ctcagtggaa cgaaaactca cgttaaggga 4980 ttttggtcat gagattatca aaaaggatct tcacctagat ccttttaaat taaaaatgaa 5040 gttttaaatc aatctaaagt atatatgagt aaacttggtc tgacagttac caatgcttaa 5100 tcagtgaggc acctatctca gcgatctgtc tatttcgttc atccatagtt gcctgactcc 5160 ccgtcgtgta gataactacg atacgggagg gcttaccatc tggccccagt gctgcaatga 5220 taccgcgaga cccacgctca ccggctccag atttatcagc aataaaccag ccagccggaa 5280 gggccgagcg cagaagtggt cctgcaactt tatccgcctc catccagtct attaattgtt 5340 gccgggaagc tagagtaagt agttcgccag ttaatagttt gcgcaacgtt gttgccattg 5400 ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc ttcattcagc tccggttccc 5460 aacgatcaag gcgagttaca tgatccccca tgttgtgcaa aaaagcggtt agctccttcg 5520 gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt atcactcatg gttatggcag 5580 cactgcataa ttctcttact gtcatgccat ccgtaagatg cttttctgtg actggtgagt 5640 actcaaccaa gtcattctga gaatagtgta tgcggcgacc gagttgctct tgcccggcgt 5700 caatacggga taataccgcg ccacatagca gaactttaaa agtgctcatc attggaaaac 5760 gttcttcggg gcgaaaactc tcaaggatct taccgctgtt gagatccagt tcgatgtaac 5820 ccactcgtgc acccaactga tcttcagcat cttttacttt caccagcgtt tctgggtgag 5880 caaaaacagg aaggcaaaat gccgcaaaaa agggaataag ggcgacacgg aaatgttgaa 5940 tactcatact cttccttttt caatattatt gaagcattta tcagggttat tgtctcatga 6000 gcggatacat atttgaatgt atttagaaaa ataaacaaat aggggttccg cgcacatttc 6060 cccgaaaagt gccacctgac gtc 6083 <210> 279 <211> 5916 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 279 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240 gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300 tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360 cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420 attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480 atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540 atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600 tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660 actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720 aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780 gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840 ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900 gtttaaacgg gccctctaga gatatcatgc cgaaaaagaa acgtaaagtg gggctcgagc 960 ccggggaaaa gccatataaa tgccccgagt gcggcaaatc attcagccaa agtagcaact 1020 tagtaagaca ccagcgcacc cataccgggg aaaagccata taaatgcccc gagtgcggca 1080 aatcattcag ccaaagtagc aacttagtaa gacaccagcg cacccatacc ggggaaaagc 1140 catataaatg ccccgagtgc ggcaaatcat tcagccaaag tagcaactta gtaagacacc 1200 agcgcaccca taccggtggc ggcagcggcg gcagcgaatt ccgcacactg gttaccttca 1260 aagatgtttt cgtggatttc acccgcgaag agtggaaact gctggatacc gcacagcaga 1320 ttgtgtatcg caacgttatg ctggaaaact acaagaatct ggttagcctg ggctatggat 1380 ccgagcagaa actcatctct gaagaagatc tggaacaaaa gttgatttca gaagaagatc 1440 tggaacagaa gctcatctct gaggaagatc tgtaagcggc cgcaagctta agtttaaacc 1500 gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg 1560 tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa 1620 ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca 1680 gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg 1740 cttctgaggc ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg 1800 gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg 1860 ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc 1920 cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc 1980 tcgaccccaa aaaacttgat tagggtgatg gttcacgtag tgggccatcg ccctgataga 2040 cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa 2100 ctggaacaac actcaaccct atctcggtct attcttttga tttataaggg attttgccga 2160 tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattaattct 2220 gtggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag gcagaagtat 2280 gcaaagcatg catctcaatt agtcagcaac caggtgtgga aagtccccag gctccccagc 2340 aggcagaagt atgcaaagca tgcatctcaa ttagtcagca accatagtcc cgcccctaac 2400 tccgcccatc ccgcccctaa ctccgcccag ttccgcccat tctccgcccc atggctgact 2460 aatttttttt atttatgcag aggccgaggc cgcctctgcc tctgagctat tccagaagta 2520 gtgaggaggc ttttttggag gcctaggctt ttgcaaaaag ctcccgggag cttgtatatc 2580 cattttcgga tctgatcaag agacaggatg aggatcgttt cgcatgattg aacaagatgg 2640 attgcacgca ggttctccgg ccgcttgggt ggagaggcta ttcggctatg actgggcaca 2700 acagacaatc ggctgctctg atgccgccgt gttccggctg tcagcgcagg ggcgcccggt 2760 tctttttgtc aagaccgacc tgtccggtgc cctgaatgaa ctgcaggacg aggcagcgcg 2820 gctatcgtgg ctggccacga cgggcgttcc ttgcgcagct gtgctcgacg ttgtcactga 2880 agcgggaagg gactggctgc tattgggcga agtgccgggg caggatctcc tgtcatctca 2940 ccttgctcct gccgagaaag tatccatcat ggctgatgca atgcggcggc tgcatacgct 3000 tgatccggct acctgcccat tcgaccacca agcgaaacat cgcatcgagc gagcacgtac 3060 tcggatggaa gccggtcttg tcgatcagga tgatctggac gaagagcatc aggggctcgc 3120 gccagccgaa ctgttcgcca ggctcaaggc gcgcatgccc gacggcgagg atctcgtcgt 3180 gacccatggc gatgcctgct tgccgaatat catggtggaa aatggccgct tttctggatt 3240 catcgactgt ggccggctgg gtgtggcgga ccgctatcag gacatagcgt tggctacccg 3300 tgatattgct gaagagcttg gcggcgaatg ggctgaccgc ttcctcgtgc tttacggtat 3360 cgccgctccc gattcgcagc gcatcgcctt ctatcgcctt cttgacgagt tcttctgagc 3420 gggactctgg ggttcgaaat gaccgaccaa gcgacgccca acctgccatc acgagatttc 3480 gattccaccg ccgccttcta tgaaaggttg ggcttcggaa tcgttttccg ggacgccggc 3540 tggatgatcc tccagcgcgg ggatctcatg ctggagttct tcgcccaccc caacttgttt 3600 attgcagctt ataatggtta caaataaagc aatagcatca caaatttcac aaataaagca 3660 tttttttcac tgcattctag ttgtggtttg tccaaactca tcaatgtatc ttatcatgtc 3720 tgtataccgt cgacctctag ctagagcttg gcgtaatcat ggtcatagct gtttcctgtg 3780 tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat aaagtgtaaa 3840 gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc actgcccgct 3900 ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg cgcggggaga 3960 ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct gcgctcggtc 4020 gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt atccacagaa 4080 tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc caggaaccgt 4140 aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga gcatcacaaa 4200 aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata ccaggcgttt 4260 ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac cggatacctg 4320 tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg taggtatctc 4380 agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc cgttcagccc 4440 gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag acacgactta 4500 tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt aggcggtgct 4560 acagagttct tgaagtggtg gcctaactac ggctacacta gaagaacagt atttggtatc 4620 tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg atccggcaaa 4680 caaaccaccg ctggtagcgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa 4740 ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac 4800 tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta 4860 aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt 4920 taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata 4980 gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc atctggcccc 5040 agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc agcaataaac 5100 cagccagccg gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag 5160 tctattaatt gttgccggga agctagagta agtagttcgc cagttaatag tttgcgcaac 5220 gttgttgcca ttgctacagg catcgtggtg tcacgctcgt cgtttggtat ggcttcattc 5280 agctccggtt cccaacgatc aaggcgagtt acatgatccc ccatgttgtg caaaaaagcg 5340 gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt gttatcactc 5400 atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag atgcttttct 5460 gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg accgagttgc 5520 tcttgcccgg cgtcaatacg ggataatacc gcgccacata gcagaacttt aaaagtgctc 5580 atcattggaa aacgttcttc ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc 5640 agttcgatgt aacccactcg tgcacccaac tgatcttcag catcttttac tttcaccagc 5700 gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa aaaagggaat aagggcgaca 5760 cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat ttatcagggt 5820 tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca aataggggtt 5880 ccgcgcacat ttccccgaaa agtgccacct gacgtc 5916 <210> 280 <211> 5897 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 280 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240 gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300 tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360 cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420 attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480 atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540 atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600 tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660 actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720 aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780 gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840 ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900 gtttaaacgg gccctctaga gatatcatgg cggcggcggt tcggatgaac atccagatgc 960 tgctggaggc ggccgactat ctggagcggc gggagagaga agctgaacat ggttatgcct 1020 ccatgttacc atacccgaaa aagaaacgta aagtggggct cgagcccggg gaaaagccat 1080 ataaatgccc cgagtgcggc aaatcattca gccaaagtag caacttagta agacaccagc 1140 gcacccatac cggggaaaag ccatataaat gccccgagtg cggcaaatca ttcagccaaa 1200 gtagcaactt agtaagacac cagcgcaccc ataccgggga aaagccatat aaatgccccg 1260 agtgcggcaa atcattcagc caaagtagca acttagtaag acaccagcgc acccataccg 1320 gtgagcagaa actcatctct gaagaagatc tggaacaaaa gttgatttca gaagaagatc 1380 tggaacagaa gctcatctct gaggaagatc tgtaagcggc cgcgaattcc accacactgg 1440 actagtggat ccgagctcgg taccaagctt aagtttaaac cgctgatcag cctcgactgt 1500 gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga 1560 aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag 1620 taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga 1680 agacaatagc aggcatgctg gggatgcggt gggctctatg gcttctgagg cggaaagaac 1740 cagctggggc tctagggggt atccccacgc gccctgtagc ggcgcattaa gcgcggcggg 1800 tgtggtggtt acgcgcagcg tgaccgctac acttgccagc gccctagcgc ccgctccttt 1860 cgctttcttc ccttcctttc tcgccacgtt cgccggcttt ccccgtcaag ctctaaatcg 1920 ggggctccct ttagggttcc gatttagtgc tttacggcac ctcgacccca aaaaacttga 1980 ttagggtgat ggttcacgta gtgggccatc gccctgatag acggtttttc gccctttgac 2040 gttggagtcc acgttcttta atagtggact cttgttccaa actggaacaa cactcaaccc 2100 tatctcggtc tattcttttg atttataagg gattttgccg atttcggcct attggttaaa 2160 aaatgagctg atttaacaaa aatttaacgc gaattaattc tgtggaatgt gtgtcagtta 2220 gggtgtggaa agtccccagg ctccccagca ggcagaagta tgcaaagcat gcatctcaat 2280 tagtcagcaa ccaggtgtgg aaagtcccca ggctccccag caggcagaag tatgcaaagc 2340 atgcatctca attagtcagc aaccatagtc ccgcccctaa ctccgcccat cccgccccta 2400 actccgccca gttccgccca ttctccgccc catggctgac taattttttt tatttatgca 2460 gaggccgagg ccgcctctgc ctctgagcta ttccagaagt agtgaggagg cttttttgga 2520 ggcctaggct tttgcaaaaa gctcccggga gcttgtatat ccattttcgg atctgatcaa 2580 gagacaggat gaggatcgtt tcgcatgatt gaacaagatg gattgcacgc aggttctccg 2640 gccgcttggg tggagaggct attcggctat gactgggcac aacagacaat cggctgctct 2700 gatgccgccg tgttccggct gtcagcgcag gggcgcccgg ttctttttgt caagaccgac 2760 ctgtccggtg ccctgaatga actgcaggac gaggcagcgc ggctatcgtg gctggccacg 2820 acgggcgttc cttgcgcagc tgtgctcgac gttgtcactg aagcgggaag ggactggctg 2880 ctattgggcg aagtgccggg gcaggatctc ctgtcatctc accttgctcc tgccgagaaa 2940 gtatccatca tggctgatgc aatgcggcgg ctgcatacgc ttgatccggc tacctgccca 3000 ttcgaccacc aagcgaaaca tcgcatcgag cgagcacgta ctcggatgga agccggtctt 3060 gtcgatcagg atgatctgga cgaagagcat caggggctcg cgccagccga actgttcgcc 3120 aggctcaagg cgcgcatgcc cgacggcgag gatctcgtcg tgacccatgg cgatgcctgc 3180 ttgccgaata tcatggtgga aaatggccgc ttttctggat tcatcgactg tggccggctg 3240 ggtgtggcgg accgctatca ggacatagcg ttggctaccc gtgatattgc tgaagagctt 3300 ggcggcgaat gggctgaccg cttcctcgtg ctttacggta tcgccgctcc cgattcgcag 3360 cgcatcgcct tctatcgcct tcttgacgag ttcttctgag cgggactctg gggttcgaaa 3420 tgaccgacca agcgacgccc aacctgccat cacgagattt cgattccacc gccgccttct 3480 atgaaaggtt gggcttcgga atcgttttcc gggacgccgg ctggatgatc ctccagcgcg 3540 gggatctcat gctggagttc ttcgcccacc ccaacttgtt tattgcagct tataatggtt 3600 acaaataaag caatagcatc acaaatttca caaataaagc atttttttca ctgcattcta 3660 gttgtggttt gtccaaactc atcaatgtat cttatcatgt ctgtataccg tcgacctcta 3720 gctagagctt ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca 3780 caattccaca caacatacga gccggaagca taaagtgtaa agcctggggt gcctaatgag 3840 tgagctaact cacattaatt gcgttgcgct cactgcccgc tttccagtcg ggaaacctgt 3900 cgtgccagct gcattaatga atcggccaac gcgcggggag aggcggtttg cgtattgggc 3960 gctcttccgc ttcctcgctc actgactcgc tgcgctcggt cgttcggctg cggcgagcgg 4020 tatcagctca ctcaaaggcg gtaatacggt tatccacaga atcaggggat aacgcaggaa 4080 agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg 4140 cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga 4200 ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg 4260 tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg 4320 gaagcgtggc gctttctcat agctcacgct gtaggtatct cagttcggtg taggtcgttc 4380 gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg 4440 gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca 4500 ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt 4560 ggcctaacta cggctacact agaagaacag tatttggtat ctgcgctctg ctgaagccag 4620 ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg 4680 gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt 4740 tgatcttttc tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg 4800 tcatgagatt atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta 4860 aatcaatcta aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg 4920 aggcacctat ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg 4980 tgtagataac tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc 5040 gagacccacg ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg 5100 agcgcagaag tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg 5160 aagctagagt aagtagttcg ccagttaata gtttgcgcaa cgttgttgcc attgctacag 5220 gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat 5280 caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc 5340 cgatcgttgt cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc 5400 ataattctct tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa 5460 ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac 5520 gggataatac cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt 5580 cggggcgaaa actctcaagg atcttaccgc tgttgagatc cagttcgatg taacccactc 5640 gtgcacccaa ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa 5700 caggaaggca aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca 5760 tactcttcct ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat 5820 acatatttga atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa 5880 aagtgccacc tgacgtc 5897 <210> 281 <211> 6198 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 281 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgttgacatt 240 gattattgac tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata 300 tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc 360 cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc 420 attgacgtca atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt 480 atcatatgcc aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt 540 atgcccagta catgacctta tgggactttc ctacttggca gtacatctac gtattagtca 600 tcgctattac catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg 660 actcacgggg atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc 720 aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg 780 gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca 840 ctgcttactg gcttatcgaa attaatacga ctcactatag ggagacccaa gctggctagc 900 gtttaaacgg gccctctaga gatatcatgc cgaaaaagaa acgtaaagtg gggctcgagc 960 ccggggaaaa gccctacaag tgccctgagt gtgggaagtc cttttcttca agacgcacgt 1020 gccgcgctca ccagcggaca cataccgggg agaagcccta taaatgtcca gaatgtggaa 1080 agtcctttag cacgtcaggg aacttagtaa gacaccagcg aactcatacc ggggagaagc 1140 catataaatg tcccgagtgt ggcaagtcct tttctagatc agataattta gtaagacatc 1200 agagaacgca caccggggaa aagccctaca agtgcccgga atgcggcaag tcttttagca 1260 ccagcggaca tttagtaaga caccagagaa cccacaccgg ggaaaaaccc tataaatgcc 1320 ccgagtgtgg taagtcattc tctcaaagcg gggatttaag aagacaccag agaacccaca 1380 ccggggaaaa accgtataaa tgtcctgagt gcggtaagtc tttttccgac tgtagagact 1440 tagcgagaca ccaacgtact cataccggtg gcggcagcgg cggcagcgaa ttcgggcgcg 1500 ccgacgcgct ggacgatttc gatctcgaca tgctgggttc tgatgccctc gatgactttg 1560 acctggatat gttgggaagc gacgcattgg atgactttga tctggacatg ctcggctccg 1620 atgctctgga cgatttcgat ctcgatatgt taattaacgg atccgagcag aaactcatct 1680 ctgaagaaga tctggaacaa aagttgattt cagaagaaga tctggaacag aagctcatct 1740 ctgaggaaga tctgtaagcg gccgcaagct taagtttaaa ccgctgatca gcctcgactg 1800 tgccttctag ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg 1860 aaggtgccac tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga 1920 gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg 1980 aagacaatag caggcatgct ggggatgcgg tgggctctat ggcttctgag gcggaaagaa 2040 ccagctgggg ctctaggggg tatccccacg cgccctgtag cggcgcatta agcgcggcgg 2100 gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg cccgctcctt 2160 tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa gctctaaatc 2220 gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc aaaaaacttg 2280 attagggtga tggttcacgt agtgggccat cgccctgata gacggttttt cgccctttga 2340 cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca acactcaacc 2400 ctatctcggt ctattctttt gatttataag ggattttgcc gatttcggcc tattggttaa 2460 aaaatgagct gatttaacaa aaatttaacg cgaattaatt ctgtggaatg tgtgtcagtt 2520 agggtgtgga aagtccccag gctccccagc aggcagaagt atgcaaagca tgcatctcaa 2580 ttagtcagca accaggtgtg gaaagtcccc aggctcccca gcaggcagaa gtatgcaaag 2640 catgcatctc aattagtcag caaccatagt cccgccccta actccgccca tcccgcccct 2700 aactccgccc agttccgccc attctccgcc ccatggctga ctaatttttt ttatttatgc 2760 agaggccgag gccgcctctg cctctgagct attccagaag tagtgaggag gcttttttgg 2820 aggcctaggc ttttgcaaaa agctcccggg agcttgtata tccattttcg gatctgatca 2880 agagacagga tgaggatcgt ttcgcatgat tgaacaagat ggattgcacg caggttctcc 2940 ggccgcttgg gtggagaggc tattcggcta tgactgggca caacagacaa tcggctgctc 3000 tgatgccgcc gtgttccggc tgtcagcgca ggggcgcccg gttctttttg tcaagaccga 3060 cctgtccggt gccctgaatg aactgcagga cgaggcagcg cggctatcgt ggctggccac 3120 gacgggcgtt ccttgcgcag ctgtgctcga cgttgtcact gaagcgggaa gggactggct 3180 gctattgggc gaagtgccgg ggcaggatct cctgtcatct caccttgctc ctgccgagaa 3240 agtatccatc atggctgatg caatgcggcg gctgcatacg cttgatccgg ctacctgccc 3300 attcgaccac caagcgaaac atcgcatcga gcgagcacgt actcggatgg aagccggtct 3360 tgtcgatcag gatgatctgg acgaagagca tcaggggctc gcgccagccg aactgttcgc 3420 caggctcaag gcgcgcatgc ccgacggcga ggatctcgtc gtgacccatg gcgatgcctg 3480 cttgccgaat atcatggtgg aaaatggccg cttttctgga ttcatcgact gtggccggct 3540 gggtgtggcg gaccgctatc aggacatagc gttggctacc cgtgatattg ctgaagagct 3600 tggcggcgaa tgggctgacc gcttcctcgt gctttacggt atcgccgctc ccgattcgca 3660 gcgcatcgcc ttctatcgcc ttcttgacga gttcttctga gcgggactct ggggttcgaa 3720 atgaccgacc aagcgacgcc caacctgcca tcacgagatt tcgattccac cgccgccttc 3780 tatgaaaggt tgggcttcgg aatcgttttc cgggacgccg gctggatgat cctccagcgc 3840 ggggatctca tgctggagtt cttcgcccac cccaacttgt ttattgcagc ttataatggt 3900 tacaaataaa gcaatagcat cacaaatttc acaaataaag catttttttc actgcattct 3960 agttgtggtt tgtccaaact catcaatgta tcttatcatg tctgtatacc gtcgacctct 4020 agctagagct tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc 4080 acaattccac acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga 4140 gtgagctaac tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg 4200 tcgtgccagc tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg 4260 cgctcttccg cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg 4320 gtatcagctc actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga 4380 aagaacatgt gagcaaaagg ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg 4440 gcgtttttcc ataggctccg cccccctgac gagcatcaca aaaatcgacg ctcaagtcag 4500 aggtggcgaa acccgacagg actataaaga taccaggcgt ttccccctgg aagctccctc 4560 gtgcgctctc ctgttccgac cctgccgctt accggatacc tgtccgcctt tctcccttcg 4620 ggaagcgtgg cgctttctca tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt 4680 cgctccaagc tgggctgtgt gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc 4740 ggtaactatc gtcttgagtc caacccggta agacacgact tatcgccact ggcagcagcc 4800 actggtaaca ggattagcag agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg 4860 tggcctaact acggctacac tagaagaaca gtatttggta tctgcgctct gctgaagcca 4920 gttaccttcg gaaaaagagt tggtagctct tgatccggca aacaaaccac cgctggtagc 4980 ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaagatcct 5040 ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta agggattttg 5100 gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa atgaagtttt 5160 aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg cttaatcagt 5220 gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg actccccgtc 5280 gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc aatgataccg 5340 cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc cggaagggcc 5400 gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa ttgttgccgg 5460 gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc cattgctaca 5520 ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg ttcccaacga 5580 tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc cttcggtcct 5640 ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat ggcagcactg 5700 cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca 5760 accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata 5820 cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct 5880 tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat gtaacccact 5940 cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg gtgagcaaaa 6000 acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg ttgaatactc 6060 atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct catgagcgga 6120 tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga 6180 aaagtgccac ctgacgtc 6198 <210> 282 <211> 10723 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 282 actcttcctt tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata 60 catatttgaa tgtatttaga aaaataaaca aataggggtt ccgcgcacat ttccccgaaa 120 agtgccacct aaattgtaag cgttaatatt ttgttaaaat tcgcgttaaa tttttgttaa 180 atcagctcat tttttaacca ataggccgaa atcggcaaaa tcccttataa atcaaaagaa 240 tagaccgaga tagggttgag tgttgttcca gtttggaaca agagtccact attaaagaac 300 gtggactcca acgtcaaagg gcgaaaaacc gtctatcagg gcgatggccc actacgtgaa 360 ccatcaccct aatcaagttt tttggggtcg aggtgccgta aagcactaaa tcggaaccct 420 aaagggagcc cccgatttag agcttgacgg ggaaagccgg cgaacgtggc gagaaaggaa 480 gggaagaaag cgaaaggagc gggcgctagg gcgctggcaa gtgtagcggt cacgctgcgc 540 gtaaccacca cacccgccgc gcttaatgcg ccgctacagg gcgcgtccca ttcgccattc 600 aggctgcgca actgttggga agggcgatcg gtgcgggcct cttcgctatt acgccagctg 660 gcgaaagggg gatgtgctgc aaggcgatta agttgggtaa cgccagggtt ttcccagtca 720 cgacgttgta aaacgacggc cagtgagcgc gcctcgttca ttcacgtttt tgaacccgtg 780 gaggacgggc agactcgcgg tgcaaatgtg ttttacagcg tgatggagca gatgaagatg 840 ctcgacacgc tgcagaacac gcagctagat taaccctaga aagataatca tattgtgacg 900 tacgttaaag ataatcatgc gtaaaattga cgcatgtgtt ttatcggtct gtatatcgag 960 gtttatttat taatttgaat agatattaag ttttattata tttacactta catactaata 1020 ataaattcaa caaacaattt atttatgttt atttatttat taaaaaaaaa caaaaactca 1080 aaatttcttc tataaagtaa caaaactttt atgagggaca gccccccccc aaagccccca 1140 gggatgtaat tacgtccctc ccccgctagg gggcagcagc gagccgcccg gggctccgct 1200 ccggtccggc gctccccccg catccccgag ccggcagcgt gcggggacag cccgggcacg 1260 gggaaggtgg cacgggatcg ctttcctctg aacgcttctc gctgctcttt gagcctgcag 1320 acacctgggg ggatacgggg aaaaggcctc caaggcctac tagtaacggc cgccagtgtg 1380 ctggaattcg cccttggtac ctgctttctc tgaccagcat tctctcccct gggcctgtgc 1440 cgctttctgt ctgcagcttg tggcctgggt cacctctacg gctggcccag atccttccct 1500 gccgcctcct tcaggttccg tcttcctcca ctccctcttc cccttgctct ctgctgtgtt 1560 gctgcccaag gatgctcttt ccggagcact tccttctcgg cgctgcacca cgtgatgtcc 1620 tctgagcgga tcctccccgt gtctgggtcc tctccgggca tctctcctcc ctcacccaac 1680 cccatgccgt cttcactcgc tgggttccct tttccttctc cttctggggc ctgtgccatc 1740 tctcgtttct taggatggcc ttctccgacg gatgtctccc ttgcgtcccg cctccccttc 1800 ttgtaggcct gcatcatcac cgtttttctg gacaacccca aagtaccccg tctccctggc 1860 tttagccacc tctccatcct cttgctttct ttgcctggac accccgttct cctgtggatt 1920 cgggtcacct ctcactcctt tcatttgggc agctccccta ccccccttac ctctctagtc 1980 tgtgctagct cttccagccc cctgtcatgg catcttccag gggtccgaga gctcagctag 2040 tcttcttcct ccaacccggg cccctatgtc cacttcagga cagcatgttt gctgcctcca 2100 gggatcctgt gtccccgagc tgggaccacc ttatattccc agggccggtt aatgtggctc 2160 tggttctggg tacttttatc tgtcccctcc accccacagt ggggcacgcg ttgacattga 2220 ttattgacta gttattaata gtaatcaatt acggggtcat tagttcatag cccatatatg 2280 gagttccgcg ttacataact tacggtaaat ggcccgcctg gctgaccgcc caacgacccc 2340 cgcccattga cgtcaataat gacgtatgtt cccatagtaa cgccaatagg gactttccat 2400 tgacgtcaat gggtggagta tttacggtaa actgcccact tggcagtaca tcaagtgtat 2460 catatgccaa gtacgccccc tattgacgtc aatgacggta aatggcccgc ctggcattat 2520 gcccagtaca tgaccttatg ggactttcct acttggcagt acatctacgt attagtcatc 2580 gctattacca tggtgatgcg gttttggcag tacatcaatg ggcgtggata gcggtttgac 2640 tcacggggat ttccaagtct ccaccccatt gacgtcaatg ggagtttgtt ttggcaccaa 2700 aatcaacggg actttccaaa atgtcgtaac aactccgccc cattgacgca aatgggcggt 2760 aggcgtgtac ggtgggaggt ctatataagc agagctctcc ctatcagtga tagagatctc 2820 cctatcagtg atagagatcg tcgacgagct cgtttagtga accgtcagat cgcctggaga 2880 cgccatccac gctgttttga cctccataga agacaccggg accgatccag cctccggact 2940 ctagcgttta aacgatatca tggcggcggc ggttcggatg aacatccaga tgctgctgga 3000 ggcggccgac tatctggagc ggcgggagag agaagctgaa catggttatg cctccatgtt 3060 accatacccg aaaaagaaac gtaaagtggg gctcgagccc ggggagaagc catataaatc 3120 tcccgagtcc ggcaagtcct tttctagatc agataattta gtaagacatc agagaacgca 3180 caccggggag aagccgtaca agagccctga atctggtaag tcattttcga gaagtgatga 3240 attagtaaga caccagcgga ctcataccgg ggaaaagccc tacaagagcc cggaaagcgg 3300 caagtctttt agcaccagcg gacatttagt aagacaccag agaacccaca ccggggagaa 3360 gccttataag tcccctgaga gcggcaaaag cttcagcgat cctggaaatt tagtaagaca 3420 ccaacgcacc cacaccgggg aaaaacctta caagtctcct gagagcggca agagcttctc 3480 tcaatcaagt tcattagtaa gacaccagag gactcatacc ggggagaaac catacaagtc 3540 cccagagagc gggaaaaact ttagtacaag cggtgagtta gtaagacacc aacgaacaca 3600 caccggtgga tccggcggca gcggcggcag cgtgagcaag ggcgaggagc tgttcaccgg 3660 ggtggtgccc atcctggtcg agctggacgg cgacgtaaac ggccacaagt tcagcgtgtc 3720 cggcgagggc gagggcgatg ccacctacgg caagctgacc ctgaagttca tctgcaccac 3780 cggcaagctg cccgtgccct ggcccaccct cgtgaccacc ctgacctacg gcgtgcagtg 3840 cttcagccgc taccccgacc acatgaagca gcacgacttc ttcaagtccg ccatgcccga 3900 aggctacgtc caggagcgca ccatcttctt caaggacgac ggcaactaca agacccgcgc 3960 cgaggtgaag ttcgagggcg acaccctggt gaaccgcatc gagctgaagg gcatcgactt 4020 caaggaggac ggcaacatcc tggggcacaa gctggagtac aactacaaca gccacaacgt 4080 ctatatcatg gccgacaagc agaagaacgg catcaaggtg aacttcaaga tccgccacaa 4140 catcgaggac ggcagcgtgc agctcgccga ccactaccag cagaacaccc ccatcggcga 4200 cggccccgtg ctgctgcccg acaaccacta cctgagcacc cagtccgccc tgagcaaaga 4260 ccccaacgag aagcgcgatc acatggtcct gctggagttc gtgaccgccg ccgggatcac 4320 tctcggcatg gacgagctgt acaagtaagc ggccgcttcg aatttaaatc ggatccctgt 4380 gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct tgaccctgga 4440 aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc attgtctgag 4500 taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg aggattggga 4560 agacaatagc aggcatgctg gggatgcggt gggctctatg gagatctgcg gccgcgaagg 4620 atctgcgatc gctccggtgc ccgtcagtgg gcagagcgca catcgcccac agtccccgag 4680 aagttggggg gaggggtcgg caattgaacg ggtgcctaga gaaggtggcg cggggtaaac 4740 tgggaaagtg atgtcgtgta ctggctccgc ctttttcccg agggtggggg agaaccgtat 4800 ataagtgcag tagtcgccgt gaacgttctt tttcgcaacg ggtttgccgc cagaacacag 4860 ctgaagcttg tgagtttggg gacccttgat tgttctttct ttttcgctat tgtaaaattc 4920 atgttatatg gagggggcaa agttttcagg gtgttgttta gaatgggaag atgtcccttg 4980 tatcaccatg gaccctcatg ataattttgt ttctttcact ttctactctg ttgacaacca 5040 ttgtctcctc ttattttctt ttcattttct gtaacttttt cgttaaactt tagcttgcat 5100 ttgtaacgaa tttttaaatt cacttttgtt tatttgtcag attgtaagta ctttctctaa 5160 tcactttttt ttcaaggcaa tcagggtata ttatattgta cttcagcaca gttttagaga 5220 acaattgtta taattaaatg ataaggtaga atatttctgc atataaattc tggctggcgt 5280 ggaaatattc ttattggtag aaacaactac atcctggtca tcatcctgcc tttctcttta 5340 tggttacaat gatatacact gtttgagatg aggataaaat actctgagtc caaaccgggc 5400 ccctctgcta accatgttca tgccttcttc tttttcctac agctcctggg caacgtgctg 5460 gttattgtgc tgtctcatca ttttggcaaa gaattgtaat acgactcact atagggcgaa 5520 ttgatatgtc tagattagat aaaagtaaag tgattaacag cgcattagag ctgcttaatg 5580 aggtcggaat cgaaggttta acaacccgta aactcgccca gaagctaggt gtagagcagc 5640 ctacattgta ttggcatgta aaaaataagc gggctttgct cgacgcctta gccattgaga 5700 tgttagatag gcaccatact cacttttgcc ctttagaagg ggaaagctgg caagattttt 5760 tacgtaataa cgctaaaagt tttagatgtg ctttactaag tcatcgcgat ggagcaaaag 5820 tacatttagg tacacggcct acagaaaaac agtatgaaac tctcgaaaat caattagcct 5880 ttttatgcca acaaggtttt tcactagaga atgcattata tgcactcagc gctgtggggc 5940 attttacttt aggttgcgta ttggaagatc aagagcatca agtcgctaaa gaagaaaggg 6000 aaacacctac tactgatagt atgccgccat tattacgaca agctatcgaa ttatttgatc 6060 accaaggtgc agagccagcc ttcttattcg gccttgaatt gatcatatgc ggattagaaa 6120 aacaacttaa atgtgaaagt gggtccgcgt acagcggatc ccgggaattc agatcttatg 6180 cgatcgaggg cagaggaagt cttctaacat gcggtgacgt ggaggagaat cccggcccta 6240 tgaccgagta caagcccacg gtgcgcctcg ccacccgcga cgacgtcccc agggccgtac 6300 gcaccctcgc cgccgcgttc gccgactacc ccgccacgcg ccacaccgtc gatccggacc 6360 gccacatcga gcgggtcacc gagctgcaag aactcttcct cacgcgcgtc gggctcgaca 6420 tcggcaaggt gtgggtcgcg gacgacggcg ccgcggtggc ggtctggacc acgccggaga 6480 gcgtcgaagc gggggcggtg ttcgccgaga tcggcccgcg catggccgag ttgagcggtt 6540 cccggctggc cgcgcagcaa cagatggaag gcctcctggc gccgcaccgg cccaaggagc 6600 ccgcgtggtt cctggccacc gtcggcgtct cgcccgacca ccagggcaag ggtctgggca 6660 gcgccgtcgt gctccccgga gtggaggcgg ccgagcgcgc cggggtgccc gccttcctgg 6720 agacctccgc gccccgcaac ctccccttct acgagcggct cggcttcacc gtcaccgccg 6780 acgtcgaggt gcccgaagga ccgcgcacct ggtgcatgac ccgcaagccc ggtgcctgaa 6840 atcaacctct ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc 6900 cttttacgct atgtggatac gctgctttaa tgcctttgta tcagttaact tgtttattgc 6960 agcttataat ggttacaaat aaagcaatag catcacaaat ttcacaaata aagcattttt 7020 ttcactgcat tctagttgtg gtttgtccaa actcatcaat gtatcttatc atgtctggaa 7080 ttgactcaaa tgatgtcaat tagtctatca gaagctatct ggtctccctt ccgggggaca 7140 agacatccct gtttaatatt taaacagcag tgttcccaaa ctgggttctt atatcccttg 7200 ctctggtcaa ccaggttgca gggtttcctg tcctcacagg aacgaagtcc ctaaagaaac 7260 agtggcagcc aggtttagcc ccggaattga ctggattcct tttttagggc ccattggtat 7320 ggtgtacact actagggaca ggattggtga cagaaaagcc ccatccttag gcctcctcct 7380 tcctagtctc ctgatattgg gtctaacccc cacctcctgt taggcagatt ccttatctgg 7440 tgacacaccc ccatttcctg gagccatctc tctccttgcc agaacctcta aggtttgctt 7500 acgatggagc cagagaggat cctgggaggg agagcttggc agggggtggg agggaagggg 7560 gggatgcgtg acctgcccgg ttctcagtgg ccaccctgcg ctaccctctc ccagaacctg 7620 agctgctctg acgcggctgt ctggtgcgtt tcactgatcc tggtgctgca gcttccttac 7680 acttcccaag aggagaagca gtttggaaaa acaaaatcag aataagttgg tcctgagttc 7740 taactttggc tcttcacctt tctagtcccc aatttatatt gttcctccgt gcgtcagttt 7800 tacctgtgag ataaggccag tagccagccc cgtcctggca gggctgtggt gaggaggggg 7860 gtgtccgtgt ggaaaactcc ctttgtgaga atggtgcgtc ctaggtgttc accaggtcgt 7920 ggccgcctct actccctttc tctttctcca tccttctttc cttaaagagt ccccagtgct 7980 atctgggaca tattcctccg cccagagcag ggtcccgctt ccctaaggcc ctgctctggg 8040 cttctgggtt tgagtccttg gcaagcccag gagaggcgct caggcttccc tgtccccctt 8100 cctcgtccac catctcatgc ccctggctct cctgcccctt ccctacaggg gttcctggct 8160 ctgctctctc gagatgcatg cgtcaatttt acgcagacta tctttctagg gttaatctag 8220 ctgcatcagg atcatatcgt cgggtctttt ttccggctca gtcatcgccc aagctggcgc 8280 tatctgggca tcggggagga agaagcccgt gccttttccc gcgaggttga agcggcatgg 8340 aaagagtttg ccgaggatga ctgctgctgc attgacgttg agcgaaaacg cacgtttacc 8400 atgatgattc gggaaggtgt ggccatgcac gcctttaacg gtgaactgtt cgttcaggcc 8460 acctgggata ccagttcgtc gcggcttttc cggacacagt tccggatggt cagcccgaag 8520 cgcatcagca acccgaacaa taccggcgac agccggaact gccgtgccgg tgtgcagatt 8580 aatgacagcg gtgcggcgct gggatattac gtcagcgagg acgggtatcc tggctggatg 8640 ccgcagaaat ggacatggat accccgtgag ttacccggcg ggcgcgcttg gcgtaatcat 8700 ggtcatagct gtttcctgtg tgaaattgtt atccgctcac aattccacac aacatacgag 8760 ccggaagcat aaagtgtaaa gcctggggtg cctaatgagt gagctaactc acattaattg 8820 cgttgcgctc actgcccgct ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa 8880 tcggccaacg cgcggggaga ggcggtttgc gtattgggcg ctcttccgct tcctcgctca 8940 ctgactcgct gcgctcggtc gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg 9000 taatacggtt atccacagaa tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc 9060 agcaaaaggc caggaaccgt aaaaaggccg cgttgctggc gtttttccat aggctccgcc 9120 cccctgacga gcatcacaaa aatcgacgct caagtcagag gtggcgaaac ccgacaggac 9180 tataaagata ccaggcgttt ccccctggaa gctccctcgt gcgctctcct gttccgaccc 9240 tgccgcttac cggatacctg tccgcctttc tcccttcggg aagcgtggcg ctttctcata 9300 gctcacgctg taggtatctc agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc 9360 acgaaccccc cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca 9420 acccggtaag acacgactta tcgccactgg cagcagccac tggtaacagg attagcagag 9480 cgaggtatgt aggcggtgct acagagttct tgaagtggtg gcctaactac ggctacacta 9540 gaaggacagt atttggtatc tgcgctctgc tgaagccagt taccttcgga aaaagagttg 9600 gtagctcttg atccggcaaa caaaccaccg ctggtagcgg tggttttttt gtttgcaagc 9660 agcagattac gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt tctacggggt 9720 ctgacgctca gtggaacgaa aactcacgtt aagggatttt ggtcatgaga ttatcaaaaa 9780 ggatcttcac ctagatcctt ttaaattaaa aatgaagttt taaatcaatc taaagtatat 9840 atgagtaaac ttggtctgac agttaccaat gcttaatcag tgaggcacct atctcagcga 9900 tctgtctatt tcgttcatcc atagttgcct gactccccgt cgtgtagata actacgatac 9960 gggagggctt accatctggc cccagtgctg caatgatacc gcgagaccca cgctcaccgg 10020 ctccagattt atcagcaata aaccagccag ccggaagggc cgagcgcaga agtggtcctg 10080 caactttatc cgcctccatc cagtctatta attgttgccg ggaagctaga gtaagtagtt 10140 cgccagttaa tagtttgcgc aacgttgttg ccattgctac aggcatcgtg gtgtcacgct 10200 cgtcgtttgg tatggcttca ttcagctccg gttcccaacg atcaaggcga gttacatgat 10260 cccccatgtt gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt gtcagaagta 10320 agttggccgc agtgttatca ctcatggtta tggcagcact gcataattct cttactgtca 10380 tgccatccgt aagatgcttt tctgtgactg gtgagtactc aaccaagtca ttctgagaat 10440 agtgtatgcg gcgaccgagt tgctcttgcc cggcgtcaat acgggataat accgcgccac 10500 atagcagaac tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga aaactctcaa 10560 ggatcttacc gctgttgaga tccagttcga tgtaacccac tcgtgcaccc aactgatctt 10620 cagcatcttt tactttcacc agcgtttctg ggtgagcaaa aacaggaagg caaaatgccg 10680 caaaaaaggg aataagggcg acacggaaat gttgaatact cat 10723 <210> 283 <211> 8068 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (1062) <223> n is a, c, g, or t <400> 283 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgtttcgaag 240 atatcgttga cattgattat tgtctagtta ttaatagtaa tcaattacgg ggtcattagt 300 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 360 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 420 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 480 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 540 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 600 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 660 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 720 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 780 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcactt aagttaaaaa 840 agactcctgc ccttcagggc ctggaagggg gcggcaccgg tactagtgtt tagtgaaccg 900 tcagatcgcc tggagacgcc atccacgctg ttttgacctc catagaagac accgggaccg 960 atccagcctc cggactctag cctcgagccc aagcttggta ccgagctcgg atccagccac 1020 catgggagtc aaagttctgt ttgccctgat ctgcatcgct gnggccgagg ccaagcccac 1080 cgagaacaac gaagacttca acatcgtggc cgtggccagc aacttcgcga ccacggatct 1140 cgatgctgac cgcgggaagt tgcccggcaa gaagctgccg ctggaggtgc tcaaagagct 1200 ggaagccaat gcccggaaag ctggctgcac caggggctgt ctgatctgcc tgtcccacat 1260 caagtgcacg cccaagatga agaagttcat cccaggacgc tgccacacct acgaaggcga 1320 caaagagtcc gcacagggcg gcataggcga ggcgatcgtc gacattcctg agattcctgg 1380 gttcaaggac ttggagcccc tggagcagtt catcgcacag gtcgatctgt gtgtggactg 1440 cacaactggc tgcctcaaag ggcttgccaa cgtgcagtgt tctgacctgc tcaagaagtg 1500 gctgccgcaa cgctgtgcga cctttgccag caagatccag ggccaggtgg acaagatcaa 1560 gggggccggt ggtgactaag cggccgcttc gagcagacat gataagatac attgatgagt 1620 ttggacaaac cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg 1680 ctattgcttt atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca 1740 ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc 1800 tctacaaatg tggtacaacc ggtctagtta ttaatagtaa tcaattacgg ggtcattagt 1860 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 1920 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 1980 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 2040 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 2100 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 2160 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 2220 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 2280 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 2340 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctctctggct 2400 aactagagaa cccactgctt actggcttat cgaaatttta attaacgttg gcaccatgct 2460 gctgctgctg ctgctgctgg gcctgaggct acagctctcc ctgggcatca tcccagttga 2520 ggaggagaac ccggacttct ggaaccgcga ggcagccgag gccctgggtg ccgccaagaa 2580 gctgcagcct gcacagacag ccgccaagaa cctcatcatc ttcctgggcg atgggatggg 2640 ggtgtctacg gtgacagctg ccaggatcct aaaagggcag aagaaggaca aactggggcc 2700 tgagataccc ctggccatgg accgcttccc atatgtggct ctgtccaaga catacaatgt 2760 agacaaacat gtgccagaca gtggagccac agccacggcc tacctgtgcg gggtcaaggg 2820 caacttccag accattggct tgagtgcagc cgcccgcttt aaccagtgca acacgacacg 2880 cggcaacgag gtcatctccg tgatgaatcg ggccaagaaa gcagggaagt cagtgggagt 2940 ggtaaccacc acacgagtgc agcacgcctc gccagccggc acctacgccc acacggtgaa 3000 ccgcaactgg tactcggacg ccgacgtgcc tgcctcggcc cgccaggagg ggtgccagga 3060 catcgctacg cagctcatct ccaacatgga cattgacgtg atcctaggtg gaggccgaaa 3120 gtacatgttt cgcatgggaa ccccagaccc tgagtaccca gatgactaca gccaaggtgg 3180 gaccaggctg gacgggaaga atctggtgca ggaatggctg gcgaagcgcc agggtgcccg 3240 gtatgtgtgg aaccgcactg agctcatgca ggcttccctg gacccgtctg tgacccatct 3300 catgggtctc tttgagcctg gagacatgaa atacgagatc caccgagact ccacactgga 3360 cccctccctg atggagatga cagaggctgc cctgcgcctg ctgagcagga acccccgcgg 3420 cttcttcctc ttcgtggagg gtggtcgcat cgaccatggt catcatgaaa gcagggctta 3480 ccgggcactg actgagacga tcatgttcga cgacgccatt gagagggcgg gccagctcac 3540 cagcgaggag gacacgctga gcctcgtcac tgccgaccac tcccacgtct tctccttcgg 3600 aggctacccc ctgcgaggga gctccatctt cgggctggcc cctggcaagg cccgggacag 3660 gaaggcctac acggtcctcc tatacggaaa cggtccaggc tatgtgctca aggacggcgc 3720 ccggccggat gttaccgaga gcgagagcgg gagccccgag tatcggcagc agtcagcagt 3780 gcccctggac gaagagaccc acgcaggcga ggacgtggcg gtgttcgcgc gcggcccgca 3840 ggcgcacctg gttcacggcg tgcaggagca gaccttcata gcgcacgtca tggccttcgc 3900 cgcctgcctg gagccctaca ccgcctgcga cctggcgccc cccgccggca ccaccgacgc 3960 cgcgcacccg ggttactcta gagtcggggc ggccggctag gtttaaaccc gctgatcagc 4020 ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 4080 gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 4140 ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 4200 ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg cttctgaggc 4260 ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg gcgcattaag 4320 cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg ccctagcgcc 4380 cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc cccgtcaagc 4440 tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc tcgaccccaa 4500 aaaacttgat tagggtgatg gttcacgtac ctagaagttc ctattccgaa gttcctattc 4560 tctagaaagt ataggaactt ccttggccaa aaagcctgaa ctcaccgcga cgtctgtcga 4620 gaagtttctg atcgaaaagt tcgacagcgt ctccgacctg atgcagctct cggagggcga 4680 agaatctcgt gctttcagct tcgatgtagg agggcgtgga tatgtcctgc gggtaaatag 4740 ctgcgccgat ggtttctaca aagatcgtta tgtttatcgg cactttgcat cggccgcgct 4800 cccgattccg gaagtgcttg acattgggga attcagcgag agcctgacct attgcatctc 4860 ccgccgtgca cagggtgtca cgttgcaaga cctgcctgaa accgaactgc ccgctgttct 4920 gcagccggtc gcggaggcca tggatgcgat cgctgcggcc gatcttagcc agacgagcgg 4980 gttcggccca ttcggaccgc aaggaatcgg tcaatacact acatggcgtg atttcatatg 5040 cgcgattgct gatccccatg tgtatcactg gcaaactgtg atggacgaca ccgtcagtgc 5100 gtccgtcgcg caggctctcg atgagctgat gctttgggcc gaggactgcc ccgaagtccg 5160 gcacctcgtg cacgcggatt tcggctccaa caatgtcctg acggacaatg gccgcataac 5220 agcggtcatt gactggagcg aggcgatgtt cggggattcc caatacgagg tcgccaacat 5280 cttcttctgg aggccgtggt tggcttgtat ggagcagcag acgcgctact tcgagcggag 5340 gcatccggag cttgcaggat cgccgcggct ccgggcgtat atgctccgca ttggtcttga 5400 ccaactctat cagagcttgg ttgacggcaa tttcgatgat gcagcttggg cgcagggtcg 5460 atgcgacgca atcgtccgat ccggagccgg gactgtcggg cgtacacaaa tcgcccgcag 5520 aagcgcggcc gtctggaccg atggctgtgt agaagtactc gccgatagtg gaaaccgacg 5580 ccccagcact cgtccgaggg caaaggaata gcacgtacta cgagatttcg attccaccgc 5640 cgccttctat gaaaggttgg gcttcggaat cgttttccgg gacgccggct ggatgatcct 5700 ccagcgcggg gatctcatgc tggagttctt cgcccacccc aacttgttta ttgcagctta 5760 taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 5820 gcattctagt tgtggtttgt ccaaactcat caatgtatct tatcatgtct gtataccgtc 5880 gacctctagc tagagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 5940 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 6000 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 6060 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 6120 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 6180 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 6240 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 6300 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 6360 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 6420 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 6480 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 6540 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 6600 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 6660 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 6720 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 6780 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 6840 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 6900 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 6960 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 7020 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 7080 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 7140 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 7200 aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 7260 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 7320 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 7380 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 7440 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 7500 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 7560 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 7620 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 7680 ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 7740 aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 7800 gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 7860 gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 7920 ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 7980 catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 8040 atttccccga aaagtgccac ctgacgtc 8068 <210> 284 <211> 8062 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (1056) <223> n is a, c, g, or t <400> 284 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgtttcgaag 240 atatcgttga cattgattat tgtctagtta ttaatagtaa tcaattacgg ggtcattagt 300 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 360 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 420 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 480 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 540 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 600 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 660 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 720 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 780 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcactt aagaaatatt 840 aaattgccca gttgggcacc atcctgaata ttatcactag tgtttagtga accgtcagat 900 cgcctggaga cgccatccac gctgttttga cctccataga agacaccggg accgatccag 960 cctccggact ctagcctcga gcccaagctt ggtaccgagc tcggatccag ccaccatggg 1020 agtcaaagtt ctgtttgccc tgatctgcat cgctgnggcc gaggccaagc ccaccgagaa 1080 caacgaagac ttcaacatcg tggccgtggc cagcaacttc gcgaccacgg atctcgatgc 1140 tgaccgcggg aagttgcccg gcaagaagct gccgctggag gtgctcaaag agctggaagc 1200 caatgcccgg aaagctggct gcaccagggg ctgtctgatc tgcctgtccc acatcaagtg 1260 cacgcccaag atgaagaagt tcatcccagg acgctgccac acctacgaag gcgacaaaga 1320 gtccgcacag ggcggcatag gcgaggcgat cgtcgacatt cctgagattc ctgggttcaa 1380 ggacttggag cccctggagc agttcatcgc acaggtcgat ctgtgtgtgg actgcacaac 1440 tggctgcctc aaagggcttg ccaacgtgca gtgttctgac ctgctcaaga agtggctgcc 1500 gcaacgctgt gcgacctttg ccagcaagat ccagggccag gtggacaaga tcaagggggc 1560 cggtggtgac taagcggccg cttcgagcag acatgataag atacattgat gagtttggac 1620 aaaccacaac tagaatgcag tgaaaaaaat gctttatttg tgaaatttgt gatgctattg 1680 ctttatttgt aaccattata agctgcaata aacaagttaa caacaacaat tgcattcatt 1740 ttatgtttca ggttcagggg gaggtgtggg aggtttttta aagcaagtaa aacctctaca 1800 aatgtggtac aaccggtcta gttattaata gtaatcaatt acggggtcat tagttcatag 1860 cccatatatg gagttccgcg ttacataact tacggtaaat ggcccgcctg gctgaccgcc 1920 caacgacccc cgcccattga cgtcaataat gacgtatgtt cccatagtaa cgccaatagg 1980 gactttccat tgacgtcaat gggtggagta tttacggtaa actgcccact tggcagtaca 2040 tcaagtgtat catatgccaa gtacgccccc tattgacgtc aatgacggta aatggcccgc 2100 ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt acatctacgt 2160 attagtcatc gctattacca tggtgatgcg gttttggcag tacatcaatg ggcgtggata 2220 gcggtttgac tcacggggat ttccaagtct ccaccccatt gacgtcaatg ggagtttgtt 2280 ttggcaccaa aatcaacggg actttccaaa atgtcgtaac aactccgccc cattgacgca 2340 aatgggcggt aggcgtgtac ggtgggaggt ctatataagc agagctctct ggctaactag 2400 agaacccact gcttactggc ttatcgaaat tttaattaac gttggcacca tgctgctgct 2460 gctgctgctg ctgggcctga ggctacagct ctccctgggc atcatcccag ttgaggagga 2520 gaacccggac ttctggaacc gcgaggcagc cgaggccctg ggtgccgcca agaagctgca 2580 gcctgcacag acagccgcca agaacctcat catcttcctg ggcgatggga tgggggtgtc 2640 tacggtgaca gctgccagga tcctaaaagg gcagaagaag gacaaactgg ggcctgagat 2700 acccctggcc atggaccgct tcccatatgt ggctctgtcc aagacataca atgtagacaa 2760 acatgtgcca gacagtggag ccacagccac ggcctacctg tgcggggtca agggcaactt 2820 ccagaccatt ggcttgagtg cagccgcccg ctttaaccag tgcaacacga cacgcggcaa 2880 cgaggtcatc tccgtgatga atcgggccaa gaaagcaggg aagtcagtgg gagtggtaac 2940 caccacacga gtgcagcacg cctcgccagc cggcacctac gcccacacgg tgaaccgcaa 3000 ctggtactcg gacgccgacg tgcctgcctc ggcccgccag gaggggtgcc aggacatcgc 3060 tacgcagctc atctccaaca tggacattga cgtgatccta ggtggaggcc gaaagtacat 3120 gtttcgcatg ggaaccccag accctgagta cccagatgac tacagccaag gtgggaccag 3180 gctggacggg aagaatctgg tgcaggaatg gctggcgaag cgccagggtg cccggtatgt 3240 gtggaaccgc actgagctca tgcaggcttc cctggacccg tctgtgaccc atctcatggg 3300 tctctttgag cctggagaca tgaaatacga gatccaccga gactccacac tggacccctc 3360 cctgatggag atgacagagg ctgccctgcg cctgctgagc aggaaccccc gcggcttctt 3420 cctcttcgtg gagggtggtc gcatcgacca tggtcatcat gaaagcaggg cttaccgggc 3480 actgactgag acgatcatgt tcgacgacgc cattgagagg gcgggccagc tcaccagcga 3540 ggaggacacg ctgagcctcg tcactgccga ccactcccac gtcttctcct tcggaggcta 3600 ccccctgcga gggagctcca tcttcgggct ggcccctggc aaggcccggg acaggaaggc 3660 ctacacggtc ctcctatacg gaaacggtcc aggctatgtg ctcaaggacg gcgcccggcc 3720 ggatgttacc gagagcgaga gcgggagccc cgagtatcgg cagcagtcag cagtgcccct 3780 ggacgaagag acccacgcag gcgaggacgt ggcggtgttc gcgcgcggcc cgcaggcgca 3840 cctggttcac ggcgtgcagg agcagacctt catagcgcac gtcatggcct tcgccgcctg 3900 cctggagccc tacaccgcct gcgacctggc gccccccgcc ggcaccaccg acgccgcgca 3960 cccgggttac tctagagtcg gggcggccgg ctaggtttaa acccgctgat cagcctcgac 4020 tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt ccttgaccct 4080 ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat cgcattgtct 4140 gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg gggaggattg 4200 ggaagacaat agcaggcatg ctggggatgc ggtgggctct atggcttctg aggcggaaag 4260 aaccagctgg ggctctaggg ggtatcccca cgcgccctgt agcggcgcat taagcgcggc 4320 gggtgtggtg gttacgcgca gcgtgaccgc tacacttgcc agcgccctag cgcccgctcc 4380 tttcgctttc ttcccttcct ttctcgccac gttcgccggc tttccccgtc aagctctaaa 4440 tcgggggctc cctttagggt tccgatttag tgctttacgg cacctcgacc ccaaaaaact 4500 tgattagggt gatggttcac gtacctagaa gttcctattc cgaagttcct attctctaga 4560 aagtatagga acttccttgg ccaaaaagcc tgaactcacc gcgacgtctg tcgagaagtt 4620 tctgatcgaa aagttcgaca gcgtctccga cctgatgcag ctctcggagg gcgaagaatc 4680 tcgtgctttc agcttcgatg taggagggcg tggatatgtc ctgcgggtaa atagctgcgc 4740 cgatggtttc tacaaagatc gttatgttta tcggcacttt gcatcggccg cgctcccgat 4800 tccggaagtg cttgacattg gggaattcag cgagagcctg acctattgca tctcccgccg 4860 tgcacagggt gtcacgttgc aagacctgcc tgaaaccgaa ctgcccgctg ttctgcagcc 4920 ggtcgcggag gccatggatg cgatcgctgc ggccgatctt agccagacga gcgggttcgg 4980 cccattcgga ccgcaaggaa tcggtcaata cactacatgg cgtgatttca tatgcgcgat 5040 tgctgatccc catgtgtatc actggcaaac tgtgatggac gacaccgtca gtgcgtccgt 5100 cgcgcaggct ctcgatgagc tgatgctttg ggccgaggac tgccccgaag tccggcacct 5160 cgtgcacgcg gatttcggct ccaacaatgt cctgacggac aatggccgca taacagcggt 5220 cattgactgg agcgaggcga tgttcgggga ttcccaatac gaggtcgcca acatcttctt 5280 ctggaggccg tggttggctt gtatggagca gcagacgcgc tacttcgagc ggaggcatcc 5340 ggagcttgca ggatcgccgc ggctccgggc gtatatgctc cgcattggtc ttgaccaact 5400 ctatcagagc ttggttgacg gcaatttcga tgatgcagct tgggcgcagg gtcgatgcga 5460 cgcaatcgtc cgatccggag ccgggactgt cgggcgtaca caaatcgccc gcagaagcgc 5520 ggccgtctgg accgatggct gtgtagaagt actcgccgat agtggaaacc gacgccccag 5580 cactcgtccg agggcaaagg aatagcacgt actacgagat ttcgattcca ccgccgcctt 5640 ctatgaaagg ttgggcttcg gaatcgtttt ccgggacgcc ggctggatga tcctccagcg 5700 cggggatctc atgctggagt tcttcgccca ccccaacttg tttattgcag cttataatgg 5760 ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 5820 tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctgtatac cgtcgacctc 5880 tagctagagc ttggcgtaat catggtcata gctgtttcct gtgtgaaatt gttatccgct 5940 cacaattcca cacaacatac gagccggaag cataaagtgt aaagcctggg gtgcctaatg 6000 agtgagctaa ctcacattaa ttgcgttgcg ctcactgccc gctttccagt cgggaaacct 6060 gtcgtgccag ctgcattaat gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg 6120 gcgctcttcc gcttcctcgc tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc 6180 ggtatcagct cactcaaagg cggtaatacg gttatccaca gaatcagggg ataacgcagg 6240 aaagaacatg tgagcaaaag gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct 6300 ggcgtttttc cataggctcc gcccccctga cgagcatcac aaaaatcgac gctcaagtca 6360 gaggtggcga aacccgacag gactataaag ataccaggcg tttccccctg gaagctccct 6420 cgtgcgctct cctgttccga ccctgccgct taccggatac ctgtccgcct ttctcccttc 6480 gggaagcgtg gcgctttctc atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt 6540 tcgctccaag ctgggctgtg tgcacgaacc ccccgttcag cccgaccgct gcgccttatc 6600 cggtaactat cgtcttgagt ccaacccggt aagacacgac ttatcgccac tggcagcagc 6660 cactggtaac aggattagca gagcgaggta tgtaggcggt gctacagagt tcttgaagtg 6720 gtggcctaac tacggctaca ctagaagaac agtatttggt atctgcgctc tgctgaagcc 6780 agttaccttc ggaaaaagag ttggtagctc ttgatccggc aaacaaacca ccgctggtag 6840 cggtggtttt tttgtttgca agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga 6900 tcctttgatc ttttctacgg ggtctgacgc tcagtggaac gaaaactcac gttaagggat 6960 tttggtcatg agattatcaa aaaggatctt cacctagatc cttttaaatt aaaaatgaag 7020 ttttaaatca atctaaagta tatatgagta aacttggtct gacagttacc aatgcttaat 7080 cagtgaggca cctatctcag cgatctgtct atttcgttca tccatagttg cctgactccc 7140 cgtcgtgtag ataactacga tacgggaggg cttaccatct ggccccagtg ctgcaatgat 7200 accgcgagac ccacgctcac cggctccaga tttatcagca ataaaccagc cagccggaag 7260 ggccgagcgc agaagtggtc ctgcaacttt atccgcctcc atccagtcta ttaattgttg 7320 ccgggaagct agagtaagta gttcgccagt taatagtttg cgcaacgttg ttgccattgc 7380 tacaggcatc gtggtgtcac gctcgtcgtt tggtatggct tcattcagct ccggttccca 7440 acgatcaagg cgagttacat gatcccccat gttgtgcaaa aaagcggtta gctccttcgg 7500 tcctccgatc gttgtcagaa gtaagttggc cgcagtgtta tcactcatgg ttatggcagc 7560 actgcataat tctcttactg tcatgccatc cgtaagatgc ttttctgtga ctggtgagta 7620 ctcaaccaag tcattctgag aatagtgtat gcggcgaccg agttgctctt gcccggcgtc 7680 aatacgggat aataccgcgc cacatagcag aactttaaaa gtgctcatca ttggaaaacg 7740 ttcttcgggg cgaaaactct caaggatctt accgctgttg agatccagtt cgatgtaacc 7800 cactcgtgca cccaactgat cttcagcatc ttttactttc accagcgttt ctgggtgagc 7860 aaaaacagga aggcaaaatg ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat 7920 actcatactc ttcctttttc aatattattg aagcatttat cagggttatt gtctcatgag 7980 cggatacata tttgaatgta tttagaaaaa taaacaaata ggggttccgc gcacatttcc 8040 ccgaaaagtg ccacctgacg tc 8062 <210> 285 <211> 8068 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (1062) <223> n is a, c, g, or t <400> 285 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgtttcgaag 240 atatcgttga cattgattat tgtctagtta ttaatagtaa tcaattacgg ggtcattagt 300 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 360 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 420 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 480 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 540 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 600 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 660 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 720 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 780 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcactt aagataaaag 840 ccaactagct tcctcttgct gtttctttag ccactaccgg tactagtgtt tagtgaaccg 900 tcagatcgcc tggagacgcc atccacgctg ttttgacctc catagaagac accgggaccg 960 atccagcctc cggactctag cctcgagccc aagcttggta ccgagctcgg atccagccac 1020 catgggagtc aaagttctgt ttgccctgat ctgcatcgct gnggccgagg ccaagcccac 1080 cgagaacaac gaagacttca acatcgtggc cgtggccagc aacttcgcga ccacggatct 1140 cgatgctgac cgcgggaagt tgcccggcaa gaagctgccg ctggaggtgc tcaaagagct 1200 ggaagccaat gcccggaaag ctggctgcac caggggctgt ctgatctgcc tgtcccacat 1260 caagtgcacg cccaagatga agaagttcat cccaggacgc tgccacacct acgaaggcga 1320 caaagagtcc gcacagggcg gcataggcga ggcgatcgtc gacattcctg agattcctgg 1380 gttcaaggac ttggagcccc tggagcagtt catcgcacag gtcgatctgt gtgtggactg 1440 cacaactggc tgcctcaaag ggcttgccaa cgtgcagtgt tctgacctgc tcaagaagtg 1500 gctgccgcaa cgctgtgcga cctttgccag caagatccag ggccaggtgg acaagatcaa 1560 gggggccggt ggtgactaag cggccgcttc gagcagacat gataagatac attgatgagt 1620 ttggacaaac cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg 1680 ctattgcttt atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca 1740 ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc 1800 tctacaaatg tggtacaacc ggtctagtta ttaatagtaa tcaattacgg ggtcattagt 1860 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 1920 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 1980 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 2040 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 2100 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 2160 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 2220 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 2280 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 2340 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctctctggct 2400 aactagagaa cccactgctt actggcttat cgaaatttta attaacgttg gcaccatgct 2460 gctgctgctg ctgctgctgg gcctgaggct acagctctcc ctgggcatca tcccagttga 2520 ggaggagaac ccggacttct ggaaccgcga ggcagccgag gccctgggtg ccgccaagaa 2580 gctgcagcct gcacagacag ccgccaagaa cctcatcatc ttcctgggcg atgggatggg 2640 ggtgtctacg gtgacagctg ccaggatcct aaaagggcag aagaaggaca aactggggcc 2700 tgagataccc ctggccatgg accgcttccc atatgtggct ctgtccaaga catacaatgt 2760 agacaaacat gtgccagaca gtggagccac agccacggcc tacctgtgcg gggtcaaggg 2820 caacttccag accattggct tgagtgcagc cgcccgcttt aaccagtgca acacgacacg 2880 cggcaacgag gtcatctccg tgatgaatcg ggccaagaaa gcagggaagt cagtgggagt 2940 ggtaaccacc acacgagtgc agcacgcctc gccagccggc acctacgccc acacggtgaa 3000 ccgcaactgg tactcggacg ccgacgtgcc tgcctcggcc cgccaggagg ggtgccagga 3060 catcgctacg cagctcatct ccaacatgga cattgacgtg atcctaggtg gaggccgaaa 3120 gtacatgttt cgcatgggaa ccccagaccc tgagtaccca gatgactaca gccaaggtgg 3180 gaccaggctg gacgggaaga atctggtgca ggaatggctg gcgaagcgcc agggtgcccg 3240 gtatgtgtgg aaccgcactg agctcatgca ggcttccctg gacccgtctg tgacccatct 3300 catgggtctc tttgagcctg gagacatgaa atacgagatc caccgagact ccacactgga 3360 cccctccctg atggagatga cagaggctgc cctgcgcctg ctgagcagga acccccgcgg 3420 cttcttcctc ttcgtggagg gtggtcgcat cgaccatggt catcatgaaa gcagggctta 3480 ccgggcactg actgagacga tcatgttcga cgacgccatt gagagggcgg gccagctcac 3540 cagcgaggag gacacgctga gcctcgtcac tgccgaccac tcccacgtct tctccttcgg 3600 aggctacccc ctgcgaggga gctccatctt cgggctggcc cctggcaagg cccgggacag 3660 gaaggcctac acggtcctcc tatacggaaa cggtccaggc tatgtgctca aggacggcgc 3720 ccggccggat gttaccgaga gcgagagcgg gagccccgag tatcggcagc agtcagcagt 3780 gcccctggac gaagagaccc acgcaggcga ggacgtggcg gtgttcgcgc gcggcccgca 3840 ggcgcacctg gttcacggcg tgcaggagca gaccttcata gcgcacgtca tggccttcgc 3900 cgcctgcctg gagccctaca ccgcctgcga cctggcgccc cccgccggca ccaccgacgc 3960 cgcgcacccg ggttactcta gagtcggggc ggccggctag gtttaaaccc gctgatcagc 4020 ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 4080 gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 4140 ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 4200 ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg cttctgaggc 4260 ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg gcgcattaag 4320 cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg ccctagcgcc 4380 cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc cccgtcaagc 4440 tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc tcgaccccaa 4500 aaaacttgat tagggtgatg gttcacgtac ctagaagttc ctattccgaa gttcctattc 4560 tctagaaagt ataggaactt ccttggccaa aaagcctgaa ctcaccgcga cgtctgtcga 4620 gaagtttctg atcgaaaagt tcgacagcgt ctccgacctg atgcagctct cggagggcga 4680 agaatctcgt gctttcagct tcgatgtagg agggcgtgga tatgtcctgc gggtaaatag 4740 ctgcgccgat ggtttctaca aagatcgtta tgtttatcgg cactttgcat cggccgcgct 4800 cccgattccg gaagtgcttg acattgggga attcagcgag agcctgacct attgcatctc 4860 ccgccgtgca cagggtgtca cgttgcaaga cctgcctgaa accgaactgc ccgctgttct 4920 gcagccggtc gcggaggcca tggatgcgat cgctgcggcc gatcttagcc agacgagcgg 4980 gttcggccca ttcggaccgc aaggaatcgg tcaatacact acatggcgtg atttcatatg 5040 cgcgattgct gatccccatg tgtatcactg gcaaactgtg atggacgaca ccgtcagtgc 5100 gtccgtcgcg caggctctcg atgagctgat gctttgggcc gaggactgcc ccgaagtccg 5160 gcacctcgtg cacgcggatt tcggctccaa caatgtcctg acggacaatg gccgcataac 5220 agcggtcatt gactggagcg aggcgatgtt cggggattcc caatacgagg tcgccaacat 5280 cttcttctgg aggccgtggt tggcttgtat ggagcagcag acgcgctact tcgagcggag 5340 gcatccggag cttgcaggat cgccgcggct ccgggcgtat atgctccgca ttggtcttga 5400 ccaactctat cagagcttgg ttgacggcaa tttcgatgat gcagcttggg cgcagggtcg 5460 atgcgacgca atcgtccgat ccggagccgg gactgtcggg cgtacacaaa tcgcccgcag 5520 aagcgcggcc gtctggaccg atggctgtgt agaagtactc gccgatagtg gaaaccgacg 5580 ccccagcact cgtccgaggg caaaggaata gcacgtacta cgagatttcg attccaccgc 5640 cgccttctat gaaaggttgg gcttcggaat cgttttccgg gacgccggct ggatgatcct 5700 ccagcgcggg gatctcatgc tggagttctt cgcccacccc aacttgttta ttgcagctta 5760 taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 5820 gcattctagt tgtggtttgt ccaaactcat caatgtatct tatcatgtct gtataccgtc 5880 gacctctagc tagagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 5940 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 6000 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 6060 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 6120 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 6180 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 6240 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 6300 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 6360 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 6420 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 6480 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 6540 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 6600 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 6660 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 6720 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 6780 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 6840 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 6900 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 6960 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 7020 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 7080 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 7140 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 7200 aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 7260 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 7320 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 7380 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 7440 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 7500 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 7560 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 7620 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 7680 ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 7740 aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 7800 gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 7860 gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 7920 ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 7980 catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 8040 atttccccga aaagtgccac ctgacgtc 8068 <210> 286 <211> 8068 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (1062) <223> n is a, c, g, or t <400> 286 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgtttcgaag 240 atatcgttga cattgattat tgtctagtta ttaatagtaa tcaattacgg ggtcattagt 300 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 360 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 420 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 480 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 540 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 600 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 660 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 720 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 780 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcactt aagttagaag 840 aaaagagcgt cgaacggcca cagccttttt ccgaaaccgg tactagtgtt tagtgaaccg 900 tcagatcgcc tggagacgcc atccacgctg ttttgacctc catagaagac accgggaccg 960 atccagcctc cggactctag cctcgagccc aagcttggta ccgagctcgg atccagccac 1020 catgggagtc aaagttctgt ttgccctgat ctgcatcgct gnggccgagg ccaagcccac 1080 cgagaacaac gaagacttca acatcgtggc cgtggccagc aacttcgcga ccacggatct 1140 cgatgctgac cgcgggaagt tgcccggcaa gaagctgccg ctggaggtgc tcaaagagct 1200 ggaagccaat gcccggaaag ctggctgcac caggggctgt ctgatctgcc tgtcccacat 1260 caagtgcacg cccaagatga agaagttcat cccaggacgc tgccacacct acgaaggcga 1320 caaagagtcc gcacagggcg gcataggcga ggcgatcgtc gacattcctg agattcctgg 1380 gttcaaggac ttggagcccc tggagcagtt catcgcacag gtcgatctgt gtgtggactg 1440 cacaactggc tgcctcaaag ggcttgccaa cgtgcagtgt tctgacctgc tcaagaagtg 1500 gctgccgcaa cgctgtgcga cctttgccag caagatccag ggccaggtgg acaagatcaa 1560 gggggccggt ggtgactaag cggccgcttc gagcagacat gataagatac attgatgagt 1620 ttggacaaac cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg 1680 ctattgcttt atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca 1740 ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc 1800 tctacaaatg tggtacaacc ggtctagtta ttaatagtaa tcaattacgg ggtcattagt 1860 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 1920 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 1980 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 2040 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 2100 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 2160 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 2220 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 2280 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 2340 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctctctggct 2400 aactagagaa cccactgctt actggcttat cgaaatttta attaacgttg gcaccatgct 2460 gctgctgctg ctgctgctgg gcctgaggct acagctctcc ctgggcatca tcccagttga 2520 ggaggagaac ccggacttct ggaaccgcga ggcagccgag gccctgggtg ccgccaagaa 2580 gctgcagcct gcacagacag ccgccaagaa cctcatcatc ttcctgggcg atgggatggg 2640 ggtgtctacg gtgacagctg ccaggatcct aaaagggcag aagaaggaca aactggggcc 2700 tgagataccc ctggccatgg accgcttccc atatgtggct ctgtccaaga catacaatgt 2760 agacaaacat gtgccagaca gtggagccac agccacggcc tacctgtgcg gggtcaaggg 2820 caacttccag accattggct tgagtgcagc cgcccgcttt aaccagtgca acacgacacg 2880 cggcaacgag gtcatctccg tgatgaatcg ggccaagaaa gcagggaagt cagtgggagt 2940 ggtaaccacc acacgagtgc agcacgcctc gccagccggc acctacgccc acacggtgaa 3000 ccgcaactgg tactcggacg ccgacgtgcc tgcctcggcc cgccaggagg ggtgccagga 3060 catcgctacg cagctcatct ccaacatgga cattgacgtg atcctaggtg gaggccgaaa 3120 gtacatgttt cgcatgggaa ccccagaccc tgagtaccca gatgactaca gccaaggtgg 3180 gaccaggctg gacgggaaga atctggtgca ggaatggctg gcgaagcgcc agggtgcccg 3240 gtatgtgtgg aaccgcactg agctcatgca ggcttccctg gacccgtctg tgacccatct 3300 catgggtctc tttgagcctg gagacatgaa atacgagatc caccgagact ccacactgga 3360 cccctccctg atggagatga cagaggctgc cctgcgcctg ctgagcagga acccccgcgg 3420 cttcttcctc ttcgtggagg gtggtcgcat cgaccatggt catcatgaaa gcagggctta 3480 ccgggcactg actgagacga tcatgttcga cgacgccatt gagagggcgg gccagctcac 3540 cagcgaggag gacacgctga gcctcgtcac tgccgaccac tcccacgtct tctccttcgg 3600 aggctacccc ctgcgaggga gctccatctt cgggctggcc cctggcaagg cccgggacag 3660 gaaggcctac acggtcctcc tatacggaaa cggtccaggc tatgtgctca aggacggcgc 3720 ccggccggat gttaccgaga gcgagagcgg gagccccgag tatcggcagc agtcagcagt 3780 gcccctggac gaagagaccc acgcaggcga ggacgtggcg gtgttcgcgc gcggcccgca 3840 ggcgcacctg gttcacggcg tgcaggagca gaccttcata gcgcacgtca tggccttcgc 3900 cgcctgcctg gagccctaca ccgcctgcga cctggcgccc cccgccggca ccaccgacgc 3960 cgcgcacccg ggttactcta gagtcggggc ggccggctag gtttaaaccc gctgatcagc 4020 ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 4080 gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 4140 ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 4200 ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg cttctgaggc 4260 ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg gcgcattaag 4320 cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg ccctagcgcc 4380 cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc cccgtcaagc 4440 tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc tcgaccccaa 4500 aaaacttgat tagggtgatg gttcacgtac ctagaagttc ctattccgaa gttcctattc 4560 tctagaaagt ataggaactt ccttggccaa aaagcctgaa ctcaccgcga cgtctgtcga 4620 gaagtttctg atcgaaaagt tcgacagcgt ctccgacctg atgcagctct cggagggcga 4680 agaatctcgt gctttcagct tcgatgtagg agggcgtgga tatgtcctgc gggtaaatag 4740 ctgcgccgat ggtttctaca aagatcgtta tgtttatcgg cactttgcat cggccgcgct 4800 cccgattccg gaagtgcttg acattgggga attcagcgag agcctgacct attgcatctc 4860 ccgccgtgca cagggtgtca cgttgcaaga cctgcctgaa accgaactgc ccgctgttct 4920 gcagccggtc gcggaggcca tggatgcgat cgctgcggcc gatcttagcc agacgagcgg 4980 gttcggccca ttcggaccgc aaggaatcgg tcaatacact acatggcgtg atttcatatg 5040 cgcgattgct gatccccatg tgtatcactg gcaaactgtg atggacgaca ccgtcagtgc 5100 gtccgtcgcg caggctctcg atgagctgat gctttgggcc gaggactgcc ccgaagtccg 5160 gcacctcgtg cacgcggatt tcggctccaa caatgtcctg acggacaatg gccgcataac 5220 agcggtcatt gactggagcg aggcgatgtt cggggattcc caatacgagg tcgccaacat 5280 cttcttctgg aggccgtggt tggcttgtat ggagcagcag acgcgctact tcgagcggag 5340 gcatccggag cttgcaggat cgccgcggct ccgggcgtat atgctccgca ttggtcttga 5400 ccaactctat cagagcttgg ttgacggcaa tttcgatgat gcagcttggg cgcagggtcg 5460 atgcgacgca atcgtccgat ccggagccgg gactgtcggg cgtacacaaa tcgcccgcag 5520 aagcgcggcc gtctggaccg atggctgtgt agaagtactc gccgatagtg gaaaccgacg 5580 ccccagcact cgtccgaggg caaaggaata gcacgtacta cgagatttcg attccaccgc 5640 cgccttctat gaaaggttgg gcttcggaat cgttttccgg gacgccggct ggatgatcct 5700 ccagcgcggg gatctcatgc tggagttctt cgcccacccc aacttgttta ttgcagctta 5760 taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 5820 gcattctagt tgtggtttgt ccaaactcat caatgtatct tatcatgtct gtataccgtc 5880 gacctctagc tagagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 5940 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 6000 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 6060 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 6120 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 6180 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 6240 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 6300 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 6360 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 6420 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 6480 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 6540 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 6600 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 6660 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 6720 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 6780 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 6840 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 6900 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 6960 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 7020 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 7080 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 7140 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 7200 aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 7260 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 7320 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 7380 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 7440 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 7500 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 7560 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 7620 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 7680 ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 7740 aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 7800 gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 7860 gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 7920 ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 7980 catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 8040 atttccccga aaagtgccac ctgacgtc 8068 <210> 287 <211> 8068 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (1062) <223> n is a, c, g, or t <400> 287 gacggatcgg gagatctccc gatcccctat ggtgcactct cagtacaatc tgctctgatg 60 ccgcatagtt aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg 120 cgagcaaaat ttaagctaca acaaggcaag gcttgaccga caattgcatg aagaatctgc 180 ttagggttag gcgttttgcg ctgcttcgcg atgtacgggc cagatatacg cgtttcgaag 240 atatcgttga cattgattat tgtctagtta ttaatagtaa tcaattacgg ggtcattagt 300 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 360 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 420 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 480 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 540 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 600 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 660 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 720 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 780 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcactt aagtggttta 840 ggaaagcagg agctattcag gaagcagggg tcctcaccgg tactagtgtt tagtgaaccg 900 tcagatcgcc tggagacgcc atccacgctg ttttgacctc catagaagac accgggaccg 960 atccagcctc cggactctag cctcgagccc aagcttggta ccgagctcgg atccagccac 1020 catgggagtc aaagttctgt ttgccctgat ctgcatcgct gnggccgagg ccaagcccac 1080 cgagaacaac gaagacttca acatcgtggc cgtggccagc aacttcgcga ccacggatct 1140 cgatgctgac cgcgggaagt tgcccggcaa gaagctgccg ctggaggtgc tcaaagagct 1200 ggaagccaat gcccggaaag ctggctgcac caggggctgt ctgatctgcc tgtcccacat 1260 caagtgcacg cccaagatga agaagttcat cccaggacgc tgccacacct acgaaggcga 1320 caaagagtcc gcacagggcg gcataggcga ggcgatcgtc gacattcctg agattcctgg 1380 gttcaaggac ttggagcccc tggagcagtt catcgcacag gtcgatctgt gtgtggactg 1440 cacaactggc tgcctcaaag ggcttgccaa cgtgcagtgt tctgacctgc tcaagaagtg 1500 gctgccgcaa cgctgtgcga cctttgccag caagatccag ggccaggtgg acaagatcaa 1560 gggggccggt ggtgactaag cggccgcttc gagcagacat gataagatac attgatgagt 1620 ttggacaaac cacaactaga atgcagtgaa aaaaatgctt tatttgtgaa atttgtgatg 1680 ctattgcttt atttgtaacc attataagct gcaataaaca agttaacaac aacaattgca 1740 ttcattttat gtttcaggtt cagggggagg tgtgggaggt tttttaaagc aagtaaaacc 1800 tctacaaatg tggtacaacc ggtctagtta ttaatagtaa tcaattacgg ggtcattagt 1860 tcatagccca tatatggagt tccgcgttac ataacttacg gtaaatggcc cgcctggctg 1920 accgcccaac gacccccgcc cattgacgtc aataatgacg tatgttccca tagtaacgcc 1980 aatagggact ttccattgac gtcaatgggt ggagtattta cggtaaactg cccacttggc 2040 agtacatcaa gtgtatcata tgccaagtac gccccctatt gacgtcaatg acggtaaatg 2100 gcccgcctgg cattatgccc agtacatgac cttatgggac tttcctactt ggcagtacat 2160 ctacgtatta gtcatcgcta ttaccatggt gatgcggttt tggcagtaca tcaatgggcg 2220 tggatagcgg tttgactcac ggggatttcc aagtctccac cccattgacg tcaatgggag 2280 tttgttttgg caccaaaatc aacgggactt tccaaaatgt cgtaacaact ccgccccatt 2340 gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat ataagcagag ctctctggct 2400 aactagagaa cccactgctt actggcttat cgaaatttta attaacgttg gcaccatgct 2460 gctgctgctg ctgctgctgg gcctgaggct acagctctcc ctgggcatca tcccagttga 2520 ggaggagaac ccggacttct ggaaccgcga ggcagccgag gccctgggtg ccgccaagaa 2580 gctgcagcct gcacagacag ccgccaagaa cctcatcatc ttcctgggcg atgggatggg 2640 ggtgtctacg gtgacagctg ccaggatcct aaaagggcag aagaaggaca aactggggcc 2700 tgagataccc ctggccatgg accgcttccc atatgtggct ctgtccaaga catacaatgt 2760 agacaaacat gtgccagaca gtggagccac agccacggcc tacctgtgcg gggtcaaggg 2820 caacttccag accattggct tgagtgcagc cgcccgcttt aaccagtgca acacgacacg 2880 cggcaacgag gtcatctccg tgatgaatcg ggccaagaaa gcagggaagt cagtgggagt 2940 ggtaaccacc acacgagtgc agcacgcctc gccagccggc acctacgccc acacggtgaa 3000 ccgcaactgg tactcggacg ccgacgtgcc tgcctcggcc cgccaggagg ggtgccagga 3060 catcgctacg cagctcatct ccaacatgga cattgacgtg atcctaggtg gaggccgaaa 3120 gtacatgttt cgcatgggaa ccccagaccc tgagtaccca gatgactaca gccaaggtgg 3180 gaccaggctg gacgggaaga atctggtgca ggaatggctg gcgaagcgcc agggtgcccg 3240 gtatgtgtgg aaccgcactg agctcatgca ggcttccctg gacccgtctg tgacccatct 3300 catgggtctc tttgagcctg gagacatgaa atacgagatc caccgagact ccacactgga 3360 cccctccctg atggagatga cagaggctgc cctgcgcctg ctgagcagga acccccgcgg 3420 cttcttcctc ttcgtggagg gtggtcgcat cgaccatggt catcatgaaa gcagggctta 3480 ccgggcactg actgagacga tcatgttcga cgacgccatt gagagggcgg gccagctcac 3540 cagcgaggag gacacgctga gcctcgtcac tgccgaccac tcccacgtct tctccttcgg 3600 aggctacccc ctgcgaggga gctccatctt cgggctggcc cctggcaagg cccgggacag 3660 gaaggcctac acggtcctcc tatacggaaa cggtccaggc tatgtgctca aggacggcgc 3720 ccggccggat gttaccgaga gcgagagcgg gagccccgag tatcggcagc agtcagcagt 3780 gcccctggac gaagagaccc acgcaggcga ggacgtggcg gtgttcgcgc gcggcccgca 3840 ggcgcacctg gttcacggcg tgcaggagca gaccttcata gcgcacgtca tggccttcgc 3900 cgcctgcctg gagccctaca ccgcctgcga cctggcgccc cccgccggca ccaccgacgc 3960 cgcgcacccg ggttactcta gagtcggggc ggccggctag gtttaaaccc gctgatcagc 4020 ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt 4080 gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca 4140 ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga 4200 ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg cttctgaggc 4260 ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg gcgcattaag 4320 cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg ccctagcgcc 4380 cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc cccgtcaagc 4440 tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc tcgaccccaa 4500 aaaacttgat tagggtgatg gttcacgtac ctagaagttc ctattccgaa gttcctattc 4560 tctagaaagt ataggaactt ccttggccaa aaagcctgaa ctcaccgcga cgtctgtcga 4620 gaagtttctg atcgaaaagt tcgacagcgt ctccgacctg atgcagctct cggagggcga 4680 agaatctcgt gctttcagct tcgatgtagg agggcgtgga tatgtcctgc gggtaaatag 4740 ctgcgccgat ggtttctaca aagatcgtta tgtttatcgg cactttgcat cggccgcgct 4800 cccgattccg gaagtgcttg acattgggga attcagcgag agcctgacct attgcatctc 4860 ccgccgtgca cagggtgtca cgttgcaaga cctgcctgaa accgaactgc ccgctgttct 4920 gcagccggtc gcggaggcca tggatgcgat cgctgcggcc gatcttagcc agacgagcgg 4980 gttcggccca ttcggaccgc aaggaatcgg tcaatacact acatggcgtg atttcatatg 5040 cgcgattgct gatccccatg tgtatcactg gcaaactgtg atggacgaca ccgtcagtgc 5100 gtccgtcgcg caggctctcg atgagctgat gctttgggcc gaggactgcc ccgaagtccg 5160 gcacctcgtg cacgcggatt tcggctccaa caatgtcctg acggacaatg gccgcataac 5220 agcggtcatt gactggagcg aggcgatgtt cggggattcc caatacgagg tcgccaacat 5280 cttcttctgg aggccgtggt tggcttgtat ggagcagcag acgcgctact tcgagcggag 5340 gcatccggag cttgcaggat cgccgcggct ccgggcgtat atgctccgca ttggtcttga 5400 ccaactctat cagagcttgg ttgacggcaa tttcgatgat gcagcttggg cgcagggtcg 5460 atgcgacgca atcgtccgat ccggagccgg gactgtcggg cgtacacaaa tcgcccgcag 5520 aagcgcggcc gtctggaccg atggctgtgt agaagtactc gccgatagtg gaaaccgacg 5580 ccccagcact cgtccgaggg caaaggaata gcacgtacta cgagatttcg attccaccgc 5640 cgccttctat gaaaggttgg gcttcggaat cgttttccgg gacgccggct ggatgatcct 5700 ccagcgcggg gatctcatgc tggagttctt cgcccacccc aacttgttta ttgcagctta 5760 taatggttac aaataaagca atagcatcac aaatttcaca aataaagcat ttttttcact 5820 gcattctagt tgtggtttgt ccaaactcat caatgtatct tatcatgtct gtataccgtc 5880 gacctctagc tagagcttgg cgtaatcatg gtcatagctg tttcctgtgt gaaattgtta 5940 tccgctcaca attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc 6000 ctaatgagtg agctaactca cattaattgc gttgcgctca ctgcccgctt tccagtcggg 6060 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 6120 tattgggcgc tcttccgctt cctcgctcac tgactcgctg cgctcggtcg ttcggctgcg 6180 gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat caggggataa 6240 cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc 6300 gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc 6360 aagtcagagg tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag 6420 ctccctcgtg cgctctcctg ttccgaccct gccgcttacc ggatacctgt ccgcctttct 6480 cccttcggga agcgtggcgc tttctcatag ctcacgctgt aggtatctca gttcggtgta 6540 ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc gttcagcccg accgctgcgc 6600 cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat cgccactggc 6660 agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt 6720 gaagtggtgg cctaactacg gctacactag aagaacagta tttggtatct gcgctctgct 6780 gaagccagtt accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc 6840 tggtagcggt ggtttttttg tttgcaagca gcagattacg cgcagaaaaa aaggatctca 6900 agaagatcct ttgatctttt ctacggggtc tgacgctcag tggaacgaaa actcacgtta 6960 agggattttg gtcatgagat tatcaaaaag gatcttcacc tagatccttt taaattaaaa 7020 atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca gttaccaatg 7080 cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg 7140 actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc 7200 aatgataccg cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc 7260 cggaagggcc gagcgcagaa gtggtcctgc aactttatcc gcctccatcc agtctattaa 7320 ttgttgccgg gaagctagag taagtagttc gccagttaat agtttgcgca acgttgttgc 7380 cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt atggcttcat tcagctccgg 7440 ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag cggttagctc 7500 cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat 7560 ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg 7620 tgagtactca accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc 7680 ggcgtcaata cgggataata ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg 7740 aaaacgttct tcggggcgaa aactctcaag gatcttaccg ctgttgagat ccagttcgat 7800 gtaacccact cgtgcaccca actgatcttc agcatctttt actttcacca gcgtttctgg 7860 gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga cacggaaatg 7920 ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct 7980 catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac 8040 atttccccga aaagtgccac ctgacgtc 8068 <210> 288 <211> 5185 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 288 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ggatatcggg gatccgaatt ctgtacaggc cttggcgcgc ctgcaggcga 4980 gctccgtcga caagcttgcg gccgcactcg agcaccacca ccaccaccac caccactaat 5040 tgattaatac ctaggctgct aaacaaagcc cgaaaggaag ctgagttggc tgctgccacc 5100 gctgagcaat aactagcata accccttggg gcctctaaac gggtcttgag gggttttttg 5160 ctgaaaggag gaactatatc cggat 5185 <210> 289 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> Synthetic construct <400> 289 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcca tataaatgtc ccgagtgtgg caagtccttt tctagatcag 5160 ataatttagt aagacatcag agaacgcaca ccggggagaa gccgtacaag tgccctgaat 5220 gtggtaagtc attttcgaga agtgatgaat tagtaagaca ccagcggact cataccgggg 5280 aaaagcccta caagtgcccg gaatgcggca agtcttttag caccagcgga catttagtaa 5340 gacaccagag aacccacacc ggggagaagc cttataagtg ccctgagtgt ggcaaaagct 5400 tcagcgatcc tggaaattta gtaagacacc aacgcaccca caccggggaa aaaccttaca 5460 agtgccctga gtgcggcaag agcttctctc aatcaagttc attagtaaga caccagagga 5520 ctcataccgg ggagaaacca tacaagtgtc cagagtgcgg gaaaagcttt agtacaagcg 5580 gtgagttagt aagacaccaa cgaacacaca ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 290 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 290 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaaaccg tacaagtgtc ctgagtgcgg gaagagtttc tccgatccgg 5160 gccacttagt aagacatcag aggacacata ccggggaaaa gccttataag tgccccgaat 5220 gcggaaagag cttctcaagg aatgatgcac ttaccgagca tcaaaggact cataccgggg 5280 aaaagcccta caagtgcccc gaatgcggga agtcttttag tcagagtgga aatcttaccg 5340 agcaccagag aacacacacc ggggaaaagc cctacaagtg tcctgagtgc ggaaagtctt 5400 tctccactag cggttcatta gtaagacacc agaggacaca caccggggaa aagccctaca 5460 agtgcccgga atgcggcaag tcttttagca ccagcggaca tttagtaaga caccagagaa 5520 cccacaccgg ggagaagccc tataaatgtc cagaatgtgg aaagtccttt agcacgtcag 5580 ggaacttagt aagacaccag cgaactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 291 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <220> <221> misc_feature <222> (5008) <223> n is a, c, g, or t <400> 291 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggnga agccctataa atgccctgaa tgcgggaaat 5040 ctttctcttc taagaaggca ctcacagaac accagcggac acacaccggg gaaaaaccgt 5100 acaagtgtcc tgagtgcggg aagagtttct ccgatccggg ccacttagta agacatcaga 5160 ggacacatac cggggagaag ccatataaat gtcccgagtg tggcaagtcc ttttctagat 5220 cagataattt agtaagacat cagagaacgc acaccgggga gaagccatat aaatgtcccg 5280 agtgtggcaa gtccttttct agatcagata atttagtaag acatcagaga acgcacaccg 5340 gggaaaagcc atataaatgc cccgagtgcg gcaaatcatt cagccaaagt agcaacttag 5400 taagacacca gcgcacccat accggggaaa aaccgtacaa gtgtcctgag tgcgggaaga 5460 gtttctccga tccgggccac ttagtaagac atcagaggac acataccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 292 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 292 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggaga aaccatacaa atgccccgag tgtggaaagt 5040 catttagtga tccaggcgca ttagtaagac atcagcggac acataccggg gagaagccat 5100 ataaatgtcc cgagtgtggc aagtcctttt ctagatcaga taatttagta agacatcaga 5160 gaacgcacac cggggagaag ccctacaagt gtccagaatg cggaaagagt ttctccagaa 5220 gtgacaaatt agtaagacac cagagaaccc ataccgggga aaaaccgtac aagtgtcctg 5280 agtgcgggaa gagtttctcc gatccgggcc acttagtaag acatcagagg acacataccg 5340 gggaaaaacc gtataaatgt cctgagtgcg gtaagtcttt ttccgactgt agagacttag 5400 cgagacacca acgtactcat accggggaga aaccatacaa atgtcccgaa tgtggcaaga 5460 gtttcagcag taaaaagcat ctcgctgagc atcagagaac tcacaccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 293 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 293 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggaga agccgtacaa gtgccctgaa tgtggtaagt 5040 cattttcgag aagtgatgaa ttagtaagac accagcggac tcataccggg gagaagccgt 5100 acaagtgccc tgaatgtggt aagtcatttt cgagaagtga tgaattagta agacaccagc 5160 ggactcatac cggggagaag ccctataaat gtccagaatg tggaaagtcc tttagcacgt 5220 cagggaactt agtaagacac cagcgaactc ataccgggga aaagccttac aaatgccccg 5280 aatgtgggaa gagtttcagc cggtctgata agctgaccga acaccagaga actcataccg 5340 gggagaagcc ctataaatgc cctgaatgtg gcaagagctt cagtactagc gggaatctca 5400 ctgaacatca gcgaactcat accggggaaa aaccttacaa gtgccctgag tgcggcaaga 5460 gcttctctca atcaagttca ttagtaagac accagaggac tcataccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 294 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 294 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggaga aaccttataa atgcccagaa tgcgggaaat 5040 cgttcagtca aagagcacat ttagaaagac atcaacggac ccacaccggg gaaaagccat 5100 ataaatgccc cgagtgcggc aaatcattca gccaaagtag caacttagta agacaccagc 5160 gcacccatac cggggaaaag ccctacaagt gtcctgagtg cggaaagtct ttctccacta 5220 gcggttcatt agtaagacac cagaggacac acaccgggga aaaaccttac aagtgccctg 5280 agtgcggcaa gagcttctct caatcaagtt cattagtaag acaccagagg actcataccg 5340 gggagaagcc atacaaatgc cctgagtgtg gaaagtcatt tagccagcga gctaatctgc 5400 gggcccacca gcggacccac accggggaaa agccatataa atgccccgag tgcggcaaat 5460 cattcagcca aagtagcaac ttagtaagac accagcgcac ccataccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 295 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic contruct <400> 295 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggaga aaccatacaa atgtcccgaa tgtggcaaga 5040 gtttcagcag taaaaagcat ctcgctgagc atcagagaac tcacaccggg gaaaaacctt 5100 acaagtgccc tgagtgcggc aagagcttct ctcaatcaag ttcattagta agacaccaga 5160 ggactcatac cggggaaaaa ccgtacaagt gtcctgagtg cgggaagagt ttctccgatc 5220 cgggccactt agtaagacat cagaggacac ataccgggga gaaaccttat aaatgcccag 5280 aatgcgggaa atcgttcagt caaagagcac atttagaaag acatcaacgg acccacaccg 5340 gggaaaagcc ctacaagtgt cctgagtgcg gaaagtcttt ctccactagc ggttcattag 5400 taagacacca gaggacacac accggggaaa aaccttacaa gtgccctgag tgcggcaaga 5460 gcttctctca atcaagttca ttagtaagac accagaggac tcataccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 296 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 296 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggaaa agccctacaa atgccccgaa tgtggtaagt 5040 ctttttctag gaacgacacc ttgacagaac accagcggac ccacaccggg gaaaagccct 5100 acaagtgtcc tgagtgcgga aagtctttct ccactagcgg ttcattagta agacaccaga 5160 ggacacacac cggggaaaaa ccgtacaagt gtcctgagtg cgggaagagt ttctccgatc 5220 cgggccactt agtaagacat cagaggacac ataccgggga gaaaccttat aaatgcccag 5280 aatgcgggaa atcgttcagt caaagagcac atttagaaag acatcaacgg acccacaccg 5340 gggaaaagcc ctacaagtgt cctgagtgcg gaaagtcttt ctccactagc ggttcattag 5400 taagacacca gaggacacac accggggaaa aaccttacaa gtgccctgag tgcggcaaga 5460 gcttctctca atcaagttca ttagtaagac accagaggac tcataccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 297 <211> 5986 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 297 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg ccgaaaaaga 4980 aacgtaaagt ggggctcgag cccggggaga aaccatacaa atgtcccgaa tgtggcaaga 5040 gtttcagcag taaaaagcat ctcgctgagc atcagagaac tcacaccggg gaaaagccct 5100 acaagtgtcc tgagtgcgga aagtctttct ccactagcgg ttcattagta agacaccaga 5160 ggacacacac cggggagaaa ccttataaat gcccagaatg cgggaaatcg ttcagtcaaa 5220 gagcacattt agaaagacat caacggaccc acaccgggga aaagccatat aaatgccccg 5280 agtgcggcaa atcattcagc caaagtagca acttagtaag acaccagcgc acccataccg 5340 gggagaaacc atacaaatgc cccgagtgtg gaaagtcatt tagtgatcca ggcgcattag 5400 taagacatca gcggacacat accggggaaa agccctacaa gtgtcctgag tgcggaaagt 5460 ctttctccac tagcggttca ttagtaagac accagaggac acacaccggt ggcggcagcg 5520 gcggcagcga attcgggcgc gccgacgcgc tggacgattt cgatctcgac atgctgggtt 5580 ctgatgccct cgatgacttt gacctggata tgttgggaag cgacgcattg gatgactttg 5640 atctggacat gctcggctcc gatgctctgg acgatttcga tctcgatatg ttaattaacg 5700 gatccgagca gaaactcatc tctgaagaag atctggaaca aaagttgatt tcagaagaag 5760 atctggaaca gaagctcatc tctgaggaag atctgtaagc ggccgcactc gagcaccacc 5820 accaccacca ccaccactaa ttgattaata cctaggctgc taaacaaagc ccgaaaggaa 5880 gctgagttgg ctgctgccac cgctgagcaa taactagcat aaccccttgg ggcctctaaa 5940 cgggtcttga ggggtttttt gctgaaagga ggaactatat ccggat 5986 <210> 298 <211> 5800 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 298 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcca tataaatgtc ccgagtgtgg caagtccttt tctagatcag 5160 ataatttagt aagacatcag agaacgcaca ccggggagaa gccgtacaag tgccctgaat 5220 gtggtaagtc attttcgaga agtgatgaat tagtaagaca ccagcggact cataccgggg 5280 aaaagcccta caagtgcccg gaatgcggca agtcttttag caccagcgga catttagtaa 5340 gacaccagag aacccacacc ggggagaagc cttataagtg ccctgagtgt ggcaaaagct 5400 tcagcgatcc tggaaattta gtaagacacc aacgcaccca caccggggaa aaaccttaca 5460 agtgccctga gtgcggcaag agcttctctc aatcaagttc attagtaaga caccagagga 5520 ctcataccgg ggagaaacca tacaagtgtc cagagtgcgg gaaaagcttt agtacaagcg 5580 gtgagttagt aagacaccaa cgaacacact aagcggccgc actcgagcac caccaccacc 5640 accaccacca ctaattgatt aatacctagg ctgctaaaca aagcccgaaa ggaagctgag 5700 ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc taaacgggtc 5760 ttgaggggtt ttttgctgaa aggaggaact atatccggat 5800 <210> 299 <211> 5860 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 299 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgccagcc gatgaaacgt ctgaccctgg 4920 gcaacgatat catggcggcg gcggttcgga tgaacatcca gatgctgctg gaggcggccg 4980 actatctgga gcggcgggag agagaagctg aacatggtta tgcctccatg ttaccatacc 5040 cgaaaaagaa acgtaaagtg gggctcgagc ccggggagaa gccatataaa tgtcccgagt 5100 gtggcaagtc cttttctaga tcagataatt tagtaagaca tcagagaacg cacaccgggg 5160 agaagccgta caagtgccct gaatgtggta agtcattttc gagaagtgat gaattagtaa 5220 gacaccagcg gactcatacc ggggaaaagc cctacaagtg cccggaatgc ggcaagtctt 5280 ttagcaccag cggacattta gtaagacacc agagaaccca caccggggag aagccttata 5340 agtgccctga gtgtggcaaa agcttcagcg atcctggaaa tttagtaaga caccaacgca 5400 cccacaccgg ggaaaaacct tacaagtgcc ctgagtgcgg caagagcttc tctcaatcaa 5460 gttcattagt aagacaccag aggactcata ccggggagaa accatacaag tgtccagagt 5520 gcgggaaaag ctttagtaca agcggtgagt tagtaagaca ccaacgaaca cacaccggtg 5580 agcagaaact catctctgaa gaagatctgg aacaaaagtt gatttcagaa gaagatctgg 5640 aacagaagct catctctgag gaagatctgt aagcggccgc actcgagcac caccaccacc 5700 accaccacca ctaattgatt aatacctagg ctgctaaaca aagcccgaaa ggaagctgag 5760 ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc taaacgggtc 5820 ttgaggggtt ttttgctgaa aggaggaact atatccggat 5860 <210> 300 <211> 5878 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 300 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcgg ttcgggcggt agccagccga 4920 tgaaacgtct gaccctgggc aacgatatca tggcggcggc ggttcggatg aacatccaga 4980 tgctgctgga ggcggccgac tatctggagc ggcgggagag agaagctgaa catggttatg 5040 cctccatgtt accatacccg aaaaagaaac gtaaagtggg gctcgagccc ggggagaagc 5100 catataaatg tcccgagtgt ggcaagtcct tttctagatc agataattta gtaagacatc 5160 agagaacgca caccggggag aagccgtaca agtgccctga atgtggtaag tcattttcga 5220 gaagtgatga attagtaaga caccagcgga ctcataccgg ggaaaagccc tacaagtgcc 5280 cggaatgcgg caagtctttt agcaccagcg gacatttagt aagacaccag agaacccaca 5340 ccggggagaa gccttataag tgccctgagt gtggcaaaag cttcagcgat cctggaaatt 5400 tagtaagaca ccaacgcacc cacaccgggg aaaaacctta caagtgccct gagtgcggca 5460 agagcttctc tcaatcaagt tcattagtaa gacaccagag gactcatacc ggggagaaac 5520 catacaagtg tccagagtgc gggaaaagct ttagtacaag cggtgagtta gtaagacacc 5580 aacgaacaca caccggtgag cagaaactca tctctgaaga agatctggaa caaaagttga 5640 tttcagaaga agatctggaa cagaagctca tctctgagga agatctgtaa gcggccgcac 5700 tcgagcacca ccaccaccac caccaccact aattgattaa tacctaggct gctaaacaaa 5760 gcccgaaagg aagctgagtt ggctgctgcc accgctgagc aataactagc ataacccctt 5820 ggggcctcta aacgggtctt gaggggtttt ttgctgaaag gaggaactat atccggat 5878 <210> 301 <211> 5890 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 301 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa catggcggcg gcggttcgga 4980 tgaacatcca gatgctgctg gaggcggccg actatctgga gcggcgggag agagaagctg 5040 aacatggtta tgcctccatg ttaccatacc cgaaaaagaa acgtaaagtg gggctcgagc 5100 ccggggagaa gccatataaa tgtcccgagt gtggcaagtc cttttctaga tcagataatt 5160 tagtaagaca tcagagaacg cacaccgggg agaagccgta caagtgccct gaatgtggta 5220 agtcattttc gagaagtgat gaattagtaa gacaccagcg gactcatacc ggggaaaagc 5280 cctacaagtg cccggaatgc ggcaagtctt ttagcaccag cggacattta gtaagacacc 5340 agagaaccca caccggggag aagccttata agtgccctga gtgtggcaaa agcttcagcg 5400 atcctggaaa tttagtaaga caccaacgca cccacaccgg ggaaaaacct tacaagtgcc 5460 ctgagtgcgg caagagcttc tctcaatcaa gttcattagt aagacaccag aggactcata 5520 ccggggagaa accatacaag tgtccagagt gcgggaaaag ctttagtaca agcggtgagt 5580 tagtaagaca ccaacgaaca cacaccggtg agcagaaact catctctgaa gaagatctgg 5640 aacaaaagtt gatttcagaa gaagatctgg aacagaagct catctctgag gaagatctgt 5700 aagcggccgc actcgagcac caccaccacc accaccacca ctaattgatt aatacctagg 5760 ctgctaaaca aagcccgaaa ggaagctgag ttggctgctg ccaccgctga gcaataacta 5820 gcataacccc ttggggcctc taaacgggtc ttgaggggtt ttttgctgaa aggaggaact 5880 atatccggat 5890 <210> 302 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 302 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaaaccc tataaatgcc ccgagtgtgg taagtcattc tctcaaagcg 5160 gggatttaag aagacaccag agaacccaca ccggggaaaa gccatataaa tgccccgagt 5220 gcggcaaatc attcagccaa agtagcaact tagtaagaca ccagcgcacc cataccgggg 5280 agaagccata taaatgtccc gagtgtggca agtccttttc tagatcagat aatttagtaa 5340 gacatcagag aacgcacacc ggggaaaagc cctataagtg tcccgaatgc ggcaagagtt 5400 ttagtactac tggcgcactc acagaacacc agcgcactca caccggggaa aagccttata 5460 agtgccccga atgcggaaag agcttctcaa ggaatgatgc acttaccgag catcaaagga 5520 ctcataccgg ggaaaaacct tataagtgtc ccgagtgcgg caagagtttc agtcacaaaa 5580 acgcacttca gaatcatcag aggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 303 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 303 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaaaccc tataaatgcc ccgagtgtgg taagtcattc tctcaaagcg 5160 gggatttaag aagacaccag agaacccaca ccggggaaaa gccatataaa tgccccgagt 5220 gcggcaaatc attcagccaa agtagcaact tagtaagaca ccagcgcacc cataccgggg 5280 agaagccata taaatgtccc gagtgtggca agtccttttc tagatcagat aatttagtaa 5340 gacatcagag aacgcacacc ggggagaagc cctataaatg ccctgaatgt ggcaagagct 5400 tcagtactag cgggaatctc actgaacatc agcgaactca taccggggaa aagccttaca 5460 aatgccccga atgtgggaag agtttcagcc ggtctgataa gctgaccgaa caccagagaa 5520 ctcataccgg ggaaaaacct tataagtgtc ccgagtgcgg caagagtttc agtcacaaaa 5580 acgcacttca gaatcatcag aggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 304 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 304 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaaacct tataaatgcc cagaatgcgg gaaatcgttc agtcaaagag 5160 cacatttaga aagacatcaa cggacccaca ccggggagaa gccatacaag tgccctgaat 5220 gtggcaagtc cttttcaaga gccgataacc tgacagaaca ccaaaggacg cataccgggg 5280 aaaaacctta taagtgtccc gagtgcggca agagtttcag tcacaaaaac gcacttcaga 5340 atcatcagag gacacatacc ggggagaagc cctataaatg tccagaatgt ggaaagtcct 5400 ttagcacgtc agggaactta gtaagacacc agcgaactca taccggggag aaaccttata 5460 aatgcccaga atgcgggaaa tcgttcagtc aaagagcaca tttagaaaga catcaacgga 5520 cccacaccgg ggaaaaacct tacaagtgcc ctgagtgcgg caagagcttc tctcaatcaa 5580 gttcattagt aagacaccag aggactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 305 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construt <400> 305 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagccc tataaatgtc cagaatgtgg aaagtccttt agcacgtcag 5160 ggaacttagt aagacaccag cgaactcata ccggggagaa gccatacaag tgccctgaat 5220 gtggcaagtc cttttcaaga gccgataacc tgacagaaca ccaaaggacg cataccgggg 5280 aaaaacctta taagtgtccc gagtgcggca agagtttcag tcacaaaaac gcacttcaga 5340 atcatcagag gacacatacc ggggaaaagc cctacaagtg tcctgagtgc ggaaagtctt 5400 tctccactag cggttcatta gtaagacacc agaggacaca caccggggag aaaccttata 5460 aatgcccaga atgcgggaaa tcgttcagtc aaagagcaca tttagaaaga catcaacgga 5520 cccacaccgg ggagaaacca tacaaatgcc ccgagtgtgg aaagtcattt agtgatccag 5580 gcgcattagt aagacatcag cggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 306 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 306 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagccc tataaatgtc cagaatgtgg aaagtccttt agcacgtcag 5160 ggaacttagt aagacaccag cgaactcata ccggggagaa gccatacaag tgccctgaat 5220 gtggcaagtc cttttcaaga gccgataacc tgacagaaca ccaaaggacg cataccgggg 5280 aaaaacctta taagtgtccc gagtgcggca agagtttcag tcacaaaaac gcacttcaga 5340 atcatcagag gacacatacc ggggaaaaac cctataaatg ccccgagtgt ggtaagtcat 5400 tctctcaaag cggggattta agaagacacc agagaaccca caccggggag aaaccttata 5460 aatgcccaga atgcgggaaa tcgttcagtc aaagagcaca tttagaaaga catcaacgga 5520 cccacaccgg ggaaaaacct tacaagtgcc ctgagtgcgg caagagcttc tctcaatcaa 5580 gttcattagt aagacaccag aggactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 307 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 307 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcct tataagtgcc ctgagtgtgg caaaagcttc agcgatcctg 5160 gaaatttagt aagacaccaa cgcacccaca ccggggagaa gccatataaa tgtcccgagt 5220 gtggcaagtc cttttctaga tcagataatt tagtaagaca tcagagaacg cacaccgggg 5280 aaaagcccta caagtgtcct gagtgcggaa agtctttctc cactagcggt tcattagtaa 5340 gacaccagag gacacacacc ggggaaaaac cgtacaagtg tcctgagtgc gggaagagtt 5400 tctccgatcc gggccactta gtaagacatc agaggacaca taccggggaa aaaccttaca 5460 agtgccctga gtgcggcaag agcttctctc aatcaagttc attagtaaga caccagagga 5520 ctcataccgg ggaaaaaccg tacaagtgtc ctgagtgcgg gaagagtttc tccgatccgg 5580 gccacttagt aagacatcag aggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 308 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 308 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcct tataagtgcc ctgagtgtgg caaaagcttc agcgatcctg 5160 gaaatttagt aagacaccaa cgcacccaca ccggggagaa gccatataaa tgtcccgagt 5220 gtggcaagtc cttttctaga tcagataatt tagtaagaca tcagagaacg cacaccgggg 5280 aaaaaccgta caagtgtcct gagtgcggga agagtttctc cgatccgggc cacttagtaa 5340 gacatcagag gacacatacc ggggaaaaac cgtacaagtg tcctgagtgc gggaagagtt 5400 tctccgatcc gggccactta gtaagacatc agaggacaca taccggggaa aaaccttaca 5460 agtgccctga gtgcggcaag agcttctctc aatcaagttc attagtaaga caccagagga 5520 ctcataccgg ggaaaaaccg tacaagtgtc ctgagtgcgg gaagagtttc tccgatccgg 5580 gccacttagt aagacatcag aggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 309 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 309 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcca tataaatgtc ccgagtgtgg caagtccttt tctagatcag 5160 ataatttagt aagacatcag agaacgcaca ccggggagaa gccgtacaag tgccctgaat 5220 gtggtaagtc attttcgaga agtgatgaat tagtaagaca ccagcggact cataccgggg 5280 agaagcctta taagtgccct gagtgtggca aaagcttcag cgatcctgga aatttagtaa 5340 gacaccaacg cacccacacc ggggagaaac cttataaatg cccagaatgc gggaaatcgt 5400 tcagtcaaag agcacattta gaaagacatc aacggaccca caccggggag aaaccttata 5460 aatgcccaga atgcgggaaa tcgttcagtc aaagagcaca tttagaaaga catcaacgga 5520 cccacaccgg ggaaaaacct tacaagtgcc ctgagtgcgg caagagcttc tctcaatcaa 5580 gttcattagt aagacaccag aggactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 310 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 310 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaaacct tacaagtgcc ctgagtgcgg caagagcttc tctcaatcaa 5160 gttcattagt aagacaccag aggactcata ccggggagaa gccctataaa tgtccagaat 5220 gtggaaagtc ctttagcacg tcagggaact tagtaagaca ccagcgaact cataccgggg 5280 agaagccgta caagtgccct gaatgtggta agtcattttc gagaagtgat gaattagtaa 5340 gacaccagcg gactcatacc ggggaaaagc cctacaagtg cccggaatgc ggcaagtctt 5400 ttagcaccag cggacattta gtaagacacc agagaaccca caccggggag aagccctata 5460 aatgtccaga atgtggaaag tcctttagca cgtcagggaa cttagtaaga caccagcgaa 5520 ctcataccgg ggagaagccg tacaagtgcc ctgaatgtgg taagtcattt tcgagaagtg 5580 atgaattagt aagacaccag cggactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 311 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 311 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaaaccg tacaagtgtc ctgagtgcgg gaagagtttc tccgatccgg 5160 gccacttagt aagacatcag aggacacata ccggggagaa gccctataaa tgtccagaat 5220 gtggaaagtc ctttagcacg tcagggaact tagtaagaca ccagcgaact cataccgggg 5280 agaagccgta caagtgccct gaatgtggta agtcattttc gagaagtgat gaattagtaa 5340 gacaccagcg gactcatacc ggggaaaagc cctacaagtg cccggaatgc ggcaagtctt 5400 ttagcaccag cggacattta gtaagacacc agagaaccca caccggggag aagccctata 5460 aatgtccaga atgtggaaag tcctttagca cgtcagggaa cttagtaaga caccagcgaa 5520 ctcataccgg ggagaagccg tacaagtgcc ctgaatgtgg taagtcattt tcgagaagtg 5580 atgaattagt aagacaccag cggactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 312 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 312 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcca tataaatgtc ccgagtgtgg caagtccttt tctagatcag 5160 ataatttagt aagacatcag agaacgcaca ccggggagaa gccctacaag tgtccagaat 5220 gcggaaagag tttctccaga agtgacaaat tagtaagaca ccagagaacc cataccgggg 5280 agaagcccta taaatgtcca gaatgtggaa agtcctttag cacgtcaggg aacttagtaa 5340 gacaccagcg aactcatacc ggggaaaaac cgtacaagtg tcctgagtgc gggaagagtt 5400 tctccgatcc gggccactta gtaagacatc agaggacaca taccggggag aaaccttata 5460 aatgcccaga atgcgggaaa tcgttcagtc aaagagcaca tttagaaaga catcaacgga 5520 cccacaccgg ggaaaagccc tacaagtgtc ctgagtgcgg aaagtctttc tccactagcg 5580 gttcattagt aagacaccag aggacacaca ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 313 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 313 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcct tataagtgcc ctgagtgtgg caaaagcttc agcgatcctg 5160 gaaatttagt aagacaccaa cgcacccaca ccggggagaa gccatataaa tgtcccgagt 5220 gtggcaagtc cttttctaga tcagataatt tagtaagaca tcagagaacg cacaccgggg 5280 aaaagcccta caagtgcccg gaatgcggca agtcttttag caccagcgga catttagtaa 5340 gacaccagag aacccacacc ggggaaaaac cgtacaagtg tcctgagtgc gggaagagtt 5400 tctccgatcc gggccactta gtaagacatc agaggacaca taccggggag aaaccttata 5460 aatgcccaga atgcgggaaa tcgttcagtc aaagagcaca tttagaaaga catcaacgga 5520 cccacaccgg ggaaaaaccg tacaagtgtc ctgagtgcgg gaagagtttc tccgatccgg 5580 gccacttagt aagacatcag aggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 314 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 314 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaagccc tacaagtgtc ctgagtgcgg aaagtctttc tccactagcg 5160 gttcattagt aagacaccag aggacacaca ccggggaaaa gccctacaag tgcccggaat 5220 gcggcaagtc ttttagcacc agcggacatt tagtaagaca ccagagaacc cacaccgggg 5280 agaagccgta caagtgccct gaatgtggta agtcattttc gagaagtgat gaattagtaa 5340 gacaccagcg gactcatacc ggggaaaagc cctacaagtg cccggaatgc ggcaagtctt 5400 ttagcaccag cggacattta gtaagacacc agagaaccca caccggggaa aagccatata 5460 aatgccccga gtgcggcaaa tcattcagcc aaagtagcaa cttagtaaga caccagcgca 5520 cccataccgg ggagaagccg tacaagtgcc ctgaatgtgg taagtcattt tcgagaagtg 5580 atgaattagt aagacaccag cggactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 315 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 315 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagcct tataagtgcc ccgaatgtgg aaagagtttc tctactaaga 5160 atagcctgac cgagcaccag cgcactcaca ccggggagaa gccctataaa tgccctgaat 5220 gcgggaaatc tttctctcaa tcaggccacc tcacagaaca ccagcggaca cacaccgggg 5280 agaagcccta taaatgccct gaatgcggga aatctttctc tcaatcaggc cacctcacag 5340 aacaccagcg gacacacacc ggggaaaagc cctacaagtg tcctgagtgc ggaaagtctt 5400 tctccactag cggttcatta gtaagacacc agaggacaca caccggggag aagccctata 5460 aatgtccaga atgtggaaag tcctttagca cgtcagggaa cttagtaaga caccagcgaa 5520 ctcataccgg ggaaaaaccc tacaagtgcc ctgagtgtgg aaagtcattt agtcgctccg 5580 accacctgac caaccatcag cggactcaca ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 316 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 316 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaagccc tataagtgtc ccgaatgcgg caagagtttt agtactactg 5160 gcgcactcac agaacaccag cgcactcaca ccggggaaaa accgtacaag tgtcctgagt 5220 gcgggaagag tttctccgat ccgggccact tagtaagaca tcagaggaca cataccgggg 5280 aaaagcccta caagtgccct gagtgtggga agtccttttc ttcaagacgc acgtgccgcg 5340 ctcaccagcg gacacatacc ggggagaagc catacaagtg ccctgaatgt ggcaagtcct 5400 tttcaagagc cgataacctg acagaacacc aaaggacgca taccggggaa aaaccgtaca 5460 agtgtcctga gtgcgggaag agtttctccg atccgggcca cttagtaaga catcagagga 5520 cacataccgg ggaaaagccc tacaagtgcc ctgagtgtgg gaagtccttt tcttcaagac 5580 gcacgtgccg cgctcaccag cggacacata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 317 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 317 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggaaaagccc tataagtgtc ccgaatgcgg caagagtttt agtactactg 5160 gcgcactcac agaacaccag cgcactcaca ccggggagaa gccttataag tgccccgaat 5220 gtggaaagag tttctctact aagaatagcc tgaccgagca ccagcgcact cacaccgggg 5280 aaaagcctta caaatgcccc gaatgtggga agagtttcag ccggtctgat aagctgaccg 5340 aacaccagag aactcatacc ggggaaaagc cttacaaatg ccccgaatgt gggaagagtt 5400 tcagccggtc tgataagctg accgaacacc agagaactca taccggggag aagccatata 5460 aatgtcccga gtgtggcaag tccttttcta gatcagataa tttagtaaga catcagagaa 5520 cgcacaccgg ggaaaagcct tacaaatgcc ccgaatgtgg gaagagtttc agccggtctg 5580 ataagctgac cgaacaccag agaactcata ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 318 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 318 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaaacct tataaatgcc cagaatgcgg gaaatcgttc agtcaaagag 5160 cacatttaga aagacatcaa cggacccaca ccggggagaa accatacaag tgtccagagt 5220 gcgggaaaag ctttagtaca agcggtgagt tagtaagaca ccaacgaaca cacaccgggg 5280 agaaaccata caagtgtcca gagtgcggga aaagctttag tacaagcggt gagttagtaa 5340 gacaccaacg aacacacacc ggggagaaac catacaaatg ccccgagtgt ggaaagtcat 5400 ttagtgatcc aggcgcatta gtaagacatc agcggacaca taccggggag aaaccataca 5460 aatgccccga gtgtggaaag tcatttagtg atccaggcgc attagtaaga catcagcgga 5520 cacataccgg ggaaaagccc tataagtgtc ccgaatgcgg caagagtttt agtactactg 5580 gcgcactcac agaacaccag cgcactcaca ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896 <210> 319 <211> 5896 <212> DNA <213> Artificial Sequence <220> <223> synthetic construct <400> 319 tggcgaatgg gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg 60 cagcgtgacc gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc 120 ctttctcgcc acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg 180 gttccgattt agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc 240 acgtagtggg ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt 300 ctttaatagt ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc 360 ttttgattta taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta 420 acaaaaattt aacgcgaatt ttaacaaaat attaacgttt acaatttcag gtggcacttt 480 tcggggaaat gtgcgcggaa cccctatttg tttatttttc taaatacatt caaatatgta 540 tccgctcatg aattaattct tagaaaaact catcgagcat caaatgaaac tgcaatttat 600 tcatatcagg attatcaata ccatattttt gaaaaagccg tttctgtaat gaaggagaaa 660 actcaccgag gcagttccat aggatggcaa gatcctggta tcggtctgcg attccgactc 720 gtccaacatc aatacaacct attaatttcc cctcgtcaaa aataaggtta tcaagtgaga 780 aatcaccatg agtgacgact gaatccggtg agaatggcaa aagtttatgc atttctttcc 840 agacttgttc aacaggccag ccattacgct cgtcatcaaa atcactcgca tcaaccaaac 900 cgttattcat tcgtgattgc gcctgagcga gacgaaatac gcgatcgctg ttaaaaggac 960 aattacaaac aggaatcgaa tgcaaccggc gcaggaacac tgccagcgca tcaacaatat 1020 tttcacctga atcaggatat tcttctaata cctggaatgc tgttttcccg gggatcgcag 1080 tggtgagtaa ccatgcatca tcaggagtac ggataaaatg cttgatggtc ggaagaggca 1140 taaattccgt cagccagttt agtctgacca tctcatctgt aacatcattg gcaacgctac 1200 ctttgccatg tttcagaaac aactctggcg catcgggctt cccatacaat cgatagattg 1260 tcgcacctga ttgcccgaca ttatcgcgag cccatttata cccatataaa tcagcatcca 1320 tgttggaatt taatcgcggc ctagagcaag acgtttcccg ttgaatatgg ctcataacac 1380 cccttgtatt actgtttatg taagcagaca gttttattgt tcatgaccaa aatcccttaa 1440 cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 1500 gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 1560 gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 1620 agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 1680 aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 1740 agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 1800 cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 1860 accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 1920 aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 1980 ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 2040 cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 2100 gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgttctt tcctgcgtta 2160 tcccctgatt ctgtggataa ccgtattacc gcctttgagt gagctgatac cgctcgccgc 2220 agccgaacga ccgagcgcag cgagtcagtg agcgaggaag cggaagagcg cctgatgcgg 2280 tattttctcc ttacgcatct gtgcggtatt tcacaccgca tatatggtgc actctcagta 2340 caatctgctc tgatgccgca tagttaagcc agtatacact ccgctatcgc tacgtgactg 2400 ggtcatggct gcgccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct 2460 gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag 2520 gttttcaccg tcatcaccga aacgcgcgag gcagctgcgg taaagctcat cagcgtggtc 2580 gtgaagcgat tcacagatgt ctgcctgttc atccgcgtcc agctcgttga gtttctccag 2640 aagcgttaat gtctggcttc tgataaagcg ggccatgtta agggcggttt tttcctgttt 2700 ggtcactgat gcctccgtgt aagggggatt tctgttcatg ggggtaatga taccgatgaa 2760 acgagagagg atgctcacga tacgggttac tgatgatgaa catgcccggt tactggaacg 2820 ttgtgagggt aaacaactgg cggtatggat gcggcgggac cagagaaaaa tcactcaggg 2880 tcaatgccag cgcttcgtta atacagatgt aggtgttcca cagggtagcc agcagcatcc 2940 tgcgatgcag atccggaaca taatggtgca gggcgctgac ttccgcgttt ccagacttta 3000 cgaaacacgg aaaccgaaga ccattcatgt tgttgctcag gtcgcagacg ttttgcagca 3060 gcagtcgctt cacgttcgct cgcgtatcgg tgattcattc tgctaaccag taaggcaacc 3120 ccgccagcct agccgggtcc tcaacgacag gagcacgatc atgctagtca tgccccgcgc 3180 ccaccggaag gagctgactg ggttgaaggc tctcaagggc atcggtcgag atcccggtgc 3240 ctaatgagtg agctaactta cattaattgc gttgcgctca ctgcccgctt tccagtcggg 3300 aaacctgtcg tgccagctgc attaatgaat cggccaacgc gcggggagag gcggtttgcg 3360 tattgggcgc cagggtggtt tttcttttca ccagtgagac gggcaacagc tgattgccct 3420 tcaccgcctg gccctgagag agttgcagca agcggtccac gctggtttgc cccagcaggc 3480 gaaaatcctg tttgatggtg gttaacggcg ggatataaca tgagctgtct tcggtatcgt 3540 cgtatcccac taccgagatg tccgcaccaa cgcgcagccc ggactcggta atggcgcgca 3600 ttgcgcccag cgccatctga tcgttggcaa ccagcatcgc agtgggaacg atgccctcat 3660 tcagcatttg catggtttgt tgaaaaccgg acatggcact ccagtcgcct tcccgttccg 3720 ctatcggctg aatttgattg cgagtgagat atttatgcca gccagccaga cgcagacgcg 3780 ccgagacaga acttaatggg cccgctaaca gcgcgatttg ctggtgaccc aatgcgacca 3840 gatgctccac gcccagtcgc gtaccgtctt catgggagaa aataatactg ttgatgggtg 3900 tctggtcaga gacatcaaga aataacgccg gaacattagt gcaggcagct tccacagcaa 3960 tggcatcctg gtcatccagc ggatagttaa tgatcagccc actgacgcgt tgcgcgagaa 4020 gattgtgcac cgccgcttta caggcttcga cgccgcttcg ttctaccatc gacaccacca 4080 cgctggcacc cagttgatcg gcgcgagatt taatcgccgc gacaatttgc gacggcgcgt 4140 gcagggccag actggaggtg gcaacgccaa tcagcaacga ctgtttgccc gccagttgtt 4200 gtgccacgcg gttgggaatg taattcagct ccgccatcgc cgcttccact ttttcccgcg 4260 ttttcgcaga aacgtggctg gcctggttca ccacgcggga aacggtctga taagagacac 4320 cggcatactc tgcgacatcg tataacgtta ctggtttcac attcaccacc ctgaattgac 4380 tctcttccgg gcgctatcat gccataccgc gaaaggtttt gcgccattcg atggtgtccg 4440 ggatctcgac gctctccctt atgcgactcc tgcattagga agcagcccag tagtaggttg 4500 aggccgttga gcaccgccgc cgcaaggaat ggtgcatgca aggagatggc gcccaacagt 4560 cccccggcca cggggcctgc caccataccc acgccgaaac aagcgctcat gagcccgaag 4620 tggcgagccc gatcttcccc atcggtgatg tcggcgatat aggcgccagc aaccgcacct 4680 gtggcgccgg tgatgccggc cacgatgcgt ccggcgtaga ggatcgagat cgatctcgat 4740 cccgcgaaat taatacgact cactataggg gaattgtgag cggataacaa ttcccctcta 4800 gaaataattt tgtttaactt taagaaggag atatacatat gcaccaccac caccaccacg 4860 gctatggccg caaaaaacgc cgccagcgcc gccgcggcta tccgtatgat gtgccggatt 4920 atgccccatg ccagccgatg aaacgtctga ccctgggcaa cgatatcatg gcggcggcgg 4980 ttcggatgaa catccagatg ctgctggagg cggccgacta tctggagcgg cgggagagag 5040 aagctgaaca tggttatgcc tccatgttac catacccgaa aaagaaacgt aaagtggggc 5100 tcgagcccgg ggagaagccc tacaagtgtc cagaatgcgg aaagagtttc tccagaagtg 5160 acaaattagt aagacaccag agaacccata ccggggagaa gccgtacaag tgccctgaat 5220 gtggtaagtc attttcgaga agtgatgaat tagtaagaca ccagcggact cataccgggg 5280 aaaaaccgta caagtgtcct gagtgcggga agagtttctc cgatccgggc cacttagtaa 5340 gacatcagag gacacatacc ggggagaagc catataaatg tcccgagtgt ggcaagtcct 5400 tttctagatc agataattta gtaagacatc agagaacgca caccggggag aagccataca 5460 agtgtcccga atgcgggaag tcattctcca gaagtgacga tttagtaaga catcagcgca 5520 cgcacaccgg ggagaaaccc tataagtgtc ccgaatgcgg gaaatcattc tctcatacag 5580 ggcatctgct cgaacatcaa aggacgcaca ccggtgagca gaaactcatc tctgaagaag 5640 atctggaaca aaagttgatt tcagaagaag atctggaaca gaagctcatc tctgaggaag 5700 atctgtaagc ggccgcactc gagcaccacc accaccacca ccaccactaa ttgattaata 5760 cctaggctgc taaacaaagc ccgaaaggaa gctgagttgg ctgctgccac cgctgagcaa 5820 taactagcat aaccccttgg ggcctctaaa cgggtcttga ggggtttttt gctgaaagga 5880 ggaactatat ccggat 5896

Claims (19)

  1. 억제(inhibitory) 또는 활성(activatory) 단백질 도메인에 융합된 유전자 프로모터를 특이적으로 표적으로 하는 다지성 아연 집게 단백질(polydactyl zinc finger protein), 핵 국소화 서열(nuclear localization sequence), 단백질 전달 영역(protein transduction domain), 및 엔도솜 특이적 프로테아제 인식 부위를 포함하는 인공 전사 인자(artificial transcription factor).
  2. 제 1항에 있어서, 상기 유전자 프로모터는 수용체 유전자의 프로모터인 인공 전사 인자.
  3. 제 1항 또는 2항에 있어서, 상기 유전자 프로모터는 핵 수용체 유전자의 프로모터인 인공 전사 인자.
  4. 제 1항에 있어서, 상기 유전자 프로모터는 단상부족성(haploinsufficient) 유전자의 프로모터인 인공 전사 인자.
  5. 제 1항 내지 4항 중 어느 한 항에 있어서, 상기 엔도좀 특이적 프로테아제 인식 부위는 카텝신 절단 부위(cathepsin cleavage site)인 인공 전사 인자.
  6. 제 5항에 있어서, 상기 엔도솜 특이적 프로테아제 인식 부위는 카텝신 B 절단 부위(cathepsin B cleavage site)인 인공 전사 인자.
  7. 제 6항에 있어서, 상기 엔도손 특이적 프로테아제 인식 부위는 서열번호 28의 카텝신 B 절단 부위인 인공 전사 인자.
  8. 제 1항에 있어서, 서열번호 64 내지 89, 144 내지 147, 156 내지 161, 174 내지 177, 188, 191 내지 193, 200 내지 205, 218 내지 220, 및 227 내지 244으로 구성된 그룹으로부터 선택되는 단백질 서열의 아연 집게 단백질을 포함하는 인공 전사 인자.
  9. 제 1항에 있어서, 최대 세 개의 개별 아연 집게 모듈이 대안적인 결합 특성을 가지는 다른 집게 모듈에 대하여 교환(exchanged) 및/또는 최대 12개의 개별 아미노산이 교환되는, 서열번호 64 내지 89, 144 내지 147, 156 내지 161, 174 내지 177, 188, 191 내지 193, 200 내지 205, 218 내지 220, 및 227 내지 244으로 구성된 그룹으로부터 선택되는 단백질 서열의 아연 집게 단백질로 구성되는 인공 전사 인자.
  10. 제 1항 내지 9항 중 어느 한 항에 있어서, 상기 억제(inhibitory) 또는 활성(activatory) 단백질 도메인은 VP16, VP64, CJ7, p65-TA1, SAD, NF-1, AP-2, SP1-A, SP1-B, Oct-1, Oct-2, Oct2-5x, MTF-1, BTEB-2, LKLF, N-KRAB, C-KRAB, SID 및 ERD으로 구성된 그룹으로부터 선택되는 인공 전사 인자.
  11. 제 1항 내지 10항 중 어느 한 항에 있어서, 상기 핵 국소화 서열(nuclear localization sequence)은 리신(lysine) 잔기에 이어서 리신 또는 아르기닌(arginine) 잔기, 이어서 임의의 아미노산, 이어서 리신 또는 아르기닌 잔기, 또는 서열번호 37의 SV40 NLS를 포함하는 염기성 아미노산의 클러스터인 인공 전사 인자.
  12. 제 1항 내지 11항에 있어서, 상기 단백질 전달 영역(protein transduction domain)은 서열번호 20의 TAT 펩티드로부터 유도된 HIV, 서열번호 21의 mT02, 서열번호 22의 mT03, 서열번호 23의 R9, 및 서열번호 24의 ANTP로 구성된 그룹으로부터 선택된 인공 전사 인자.
  13. 제 1 내지 12항 중 어느 한 항에 있어서, 엔도솜 프로테아제-민감 링커(endosomal protease-sensitive linker)을 통해 서열번호 25 내지 27의 융해성 펩티드(fusogenic peptide)에 연결된 인공 전사 인자.
  14. 제 1항 내지 13항 중 어느 한 항에 있어서, 폴리에틸렌 글리콜 잔기(polyethylene glycol residue)를 추가적으로 포함하는 인공 전사 인자.
  15. 제 1항 내지 14항 중 어느 한 항에 있어서, 유전자 프로모터로부터 발현을 증가 또는 감소시키는데 사용하기 위한 인공 전사 인자.
  16. 제 1항 내지 14항 중 어느 한 항에 따른 인공 전사 인자를 포함하는 약학적 조성물.
  17. 제 1항 내지 13항 중 어느 한 항의 인공 전사 인자의 생산에 사용하기 위한 서열번호 289 내지 319의 발현 구조체를 포함하는 대장균(E. coli) 숙주 세포.
  18. 제 1항 내지 14항 중 어느 한 항에 있어서, 유전자 발현의 조절이 치료적으로 유익한(therapeutically beneficial) 질병의 치료에 사용하기 위한 인공 전사 인자.
  19. 제 1항 내지 14항 중 어느 한 항에 따른 인공 전사 인자를 이를 필요로 하는 환자에게 치료학적으로 유효한 양을 투여하는 것을 포함하는, 유전자 발현의 조절이 치료적으로 유익한 질병을 치료하는 방법.

KR1020157031592A 2013-04-03 2014-04-02 엔도솜 포집을 극복하기 위해 설계된 인공 전사 인자 KR20160002880A (ko)

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