CN116479095A - Ago protein/PIWI domain-containing protein-based nucleic acid polymerase reaction method and application - Google Patents

Ago protein/PIWI domain-containing protein-based nucleic acid polymerase reaction method and application Download PDF

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CN116479095A
CN116479095A CN202210042552.3A CN202210042552A CN116479095A CN 116479095 A CN116479095 A CN 116479095A CN 202210042552 A CN202210042552 A CN 202210042552A CN 116479095 A CN116479095 A CN 116479095A
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Hangzhou Weibian Biotechnology Co ltd
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/6848—Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention discloses a nucleic acid polymerase reaction method based on Ago protein and/or protein containing PIWI structural domain, which comprises the following steps: DNA or RNA is taken as a template, ago protein and/or protein containing a PIWI structural domain promotes primer specific targeting binding with a template complementary to the sequence of the Ago protein or the protein, so that polymerization activity of polymerase or reverse transcriptase is initiated, dNTP is taken as a raw material, and complementary strand of the template is synthesized according to a base complementary pairing principle and a semi-reserved replication principle. Nucleic acid amplification is achieved in duplicate. The invention has high detection limit and amplification efficiency of PCR; the sensitivity is high, and trace target nucleic acid can be detected in a hybrid template; the flexibility is strong, and the DNA template and the RNA template can be identified; can react at higher temperature or at normal temperature; the method is suitable for both temperature-variable amplification and constant-temperature amplification; the amplification can be carried out at different temperatures without being limited by the annealing temperature of the primer; the primer consumption is reduced, and the detection time is shortened. The invention has wide application prospect.

Description

Ago protein/PIWI domain-containing protein-based nucleic acid polymerase reaction method and application
Technical Field
The invention belongs to the technical field of biology, and relates to a nucleic acid polymerase reaction method based on Ago protein and/or protein containing PIWI structural domain and application thereof.
Background
Argonaute can specifically target either target ssDNA or target RNA under the guidance of gDNA or gRNA. The biggest capacity of Argonaute is to find and bind specifically and rapidly to a target, which is a single-stranded state, under guidance of guide. Eukaryotic RNAi takes advantage of this property of argonaute, and human Ago2 can accurately and rapidly find targettRNA in cellular RNA ocean using siRNA.
The conventional PCR technique mainly comprises three basic reaction steps: (1) denaturation of template DNA: after heating for a certain time, the double-stranded DNA of the template DNA or the double-stranded DNA formed by PCR amplification is dissociated into single strands; (2) annealing (renaturation) of template DNA to primer: the temperature is reduced to about 55 ℃, and the primer is matched and combined with the complementary sequence of the template DNA single strand; (3) primer extension: under the action of DNA polymerase (such as Taq DNA polymerase) at 72 deg.C, dNTP is used as reaction raw material, target sequence is used as template, according to the base complementary pairing and semi-preserving replication principle, a new semi-preserving replication chain complementary with template DNA chain is synthesized, and the three processes of repeated cyclic denaturation, annealing and extension can obtain more 'semi-preserving replication chains', and said new chain can become template for next cycle.
The detection limit of the traditional PCR theory can reach single copy, but false negative is very easy to occur when the concentration of the template is low or the template is mixed, for example, a new coronavirus infected person is detected by using a PCR method, and the virus is often detected to be carried after 10 times of detection, and the virus is likely to be widely spread after a long time. The reason that the traditional PCR is extremely easy to generate false negative is that the annealing of the template DNA and the primer is that the molecular thermal motion is naturally close to match, and when the low template concentration or the mixed template is detected, the collision probability of the primer and the template is greatly reduced, so that the primer and the template cannot be amplified.
Nucleic acid in vitro amplification technology is a fundamental and necessary technical means of life science research. Polymerase Chain Reaction (PCR) is the most widely used technique for nucleic acid amplification at present. However, PCR itself requires a high-precision and expensive temperature cycler, a skilled and stable operator, a small detection throughput, a low efficiency in detecting the promiscuous template, and a possibility of false negative, and the PCR-based nucleic acid detection is limited to a central laboratory, which has a great limitation on rapid detection in the field.
In recent years, the advent of isothermal amplification technology has been attracting attention because it can solve the limitations of PCR technology. The common isothermal amplification techniques are the following: depending on the helicase isothermal amplification (HDA), loop-mediated isothermal amplification (LAMP), recombinase Polymerase Amplification (RPA), etc.
Depending on the helicase isothermal gene amplification technique (Helicase Dependent Isothermal DNA Amplification, HDA), this method uses a helicase to convert double stranded nucleic acids into single stranded nucleic acids, replacing the thermal denaturation method of traditional PCR, allowing the entire reaction to proceed at isothermal temperature. The helicase opens the double strand and the single stranded DNA binding protein (SSB) remains single stranded and the primer anneals to the single stranded template and the polymerase initiates polymerization. The method requires strict design of primer annealing temperature, if the primer is unsuitable, the primer is difficult to combine with a template to influence amplification, and the template and an amplification product have the best effect of less than 150 bp.
Loop-mediated isothermal amplification (LoopMedated IsothermalAmplification, LAMP) technology, which uses 4 specific primers to respectively identify 6 specific regions of target DNA, and realizes rapid isothermal amplification of DNA through 2 loop structures and strand displacement reaction. The LAMP reaction process includes a dumbbell template synthesis stage, a cyclic amplification stage, an elongation and recirculation stage. The special feature is the design of primer, it includes 2 inner primers FIP, BIP and 2 outer primers F3, B3, wherein two inner primers will form stem loop structure by themselves after extending on the template, two outer primers will displace the extending inner primer under the action of polymerase extension. The method has the advantages of rapid reaction, effective amplification detection of 1-10 copies of target genes within one hour, strong specificity, constant temperature detection and no need of special instruments. However, the four primers are difficult to design, the requirement on the designer is high, the dissociation of double chains in the process is dependent on adding a melting temperature regulator, and a large amount of amplified products containing repeated structures are easy to form aerosol, so that false positive results are caused.
Recombinase polymerase amplification (Recombinase polymerase amplification, RPA), the basic principle of which relies on a natural cellular process called homologous recombination, in the presence of ATP and aggregation agent (high molecular weight polyethylene glycol), T4uvsX (recombinase protein) is combined with primers with the aid of T4 UvsY (loading factor) to form a recombinase-primer complex, which then searches for homologous sequences in double-stranded DNA and strand exchanges at homologous sites by the primers, prevents detachment of inserted primers by branch migration, and single-stranded binding proteins stably displace the DNA strands, and finally recombinase-cleaves the strand-displacement-capable DNA polymerase-binding primer for synthesis. The method has complex reaction, numerous components and high price, the design principle of the primer is not determined so far, and the primer with good effect mainly depends on a large number of synthesis and screening, and has great cost and time consumption. When the RPA product is detected by agarose gel electrophoresis, the DNA binding protein, buffer solution in a reaction system and the like are required to be removed, so that the detection time and the detection cost are increased. The single-stranded template cannot be detected directly. At present, the recombinant enzyme is only effective at 37 ℃, and the application of RPA at other temperatures is limited.
Disclosure of Invention
The invention provides a nucleic acid polymerase reaction method and a reaction system based on Ago protein and/or PIWI structural domain-containing protein for the first time and application. The invention also provides a method for amplifying nucleic acid by using Ago and/or a protein-PCR containing a PIWI domain, which comprises, but is not limited to, a method for amplifying temperature-changing nucleic acid by using Ago and/or a protein-PCR containing a PIWI domain, a method for amplifying constant temperature nucleic acid by using Ago and/or a protein-PCR containing a PIWI domain, a method for amplifying nucleic acid by using Ago and/or a protein-RT-PCR containing a PIWI domain, a method for amplifying nucleic acid by using a single-tube multi-site Ago and/or a protein-PCR containing a PIWI domain, and the like, and a method for amplifying nucleic acid by using Ago and/or a protein-primer binary complex containing a PIWI domain. The invention also provides Ago protein and/or a protein-primer binary complex containing a PIWI structural domain, a composition, a reagent or a kit, and the like, and application thereof.
The invention provides a nucleic acid polymerase reaction method based on Ago protein and/or PIWI structural domain-containing protein, which comprises the following steps: DNA or RNA is taken as a template, ago protein and/or protein containing a PIWI structural domain promotes a primer to be quickly and specifically bound with a template complementary to the sequence of the Ago protein or the protein, so that the polymerization activity of polymerase or reverse transcriptase is initiated, dNTP is taken as a raw material, and the complementary strand of the template is synthesized according to a base complementary pairing principle and a semi-reserved replication principle.
In the present invention, the "Argonaute" is a family of nucleic acid binding proteins that are ubiquitous in bacterial, plant, archaea and animal cells.
In the present invention, the "PIWI domain-containing protein" is a protein that is identified as comprising a PIWI-like domain by alignment of the protein sequences of various databases (e.g., NCBI); the PIWI-like domain is used to bind nucleic acids.
In the present invention, the Ago protein and the "PIWI domain-containing protein" may each independently exist or may contain a cross overlap.
In the method provided by the invention, the steps are repeated at least more than once, the reaction is repeated for a plurality of times, and the Ago protein and/or the protein containing the PIWI structural domain and the nucleic acid polymerase exist in the same reaction system to carry out the nucleic acid polymerase chain reaction, so that the nucleic acid amplification is realized. In particular embodiments, the steps are repeated one or more times and the nucleic acid replication (gene replication) reaction is repeated until the desired degree of nucleic acid amplification is achieved.
In the present invention, the Ago protein and/or the PIWI domain-containing protein includes, but is not limited to, any Ago protein and/or PIWI domain-containing protein that promotes or enhances the complementary binding of the primer to the template. In some embodiments, it includes, but is not limited to, any protein capable of promoting or enhancing the speed, efficiency, accuracy, sensitivity, etc., of matching of the primer to the template for complementary binding. In some embodiments, it includes, but is not limited to, any protein that contains structural or functional identity or similarity to an Ago protein and/or PIWI domain. It may also be a protein comprising a nucleic acid sequence or an amino acid sequence comprising a PIWI domain.
In some embodiments, the Ago protein may be as set forth in figure 31.
Preferably, the Ago proteins include eukaryotic Ago proteins and prokaryotic Ago proteins.
Preferably, the Ago protein and/or the PIWI domain-containing protein is targeted to the binding template rapidly and specifically under the guidance of primers.
More preferably, the Ago protein and/or the PIWI domain-containing protein binds to the primer to form a binary complex rapid specific targeting binding template.
Preferably, the reaction method does not need an annealing step or an annealing enzyme, so that the detection limit and the amplification efficiency of PCR can be remarkably improved.
Preferably, the Ago proteins include proteins that are noted to contain PIWI-like domains by alignment of the protein sequences of each large database (e.g., NCBI); the PIWI-like domain is used to bind nucleic acids.
Preferably, the Ago protein and/or PIWI domain-containing protein is a protein that is capable of being active under conditions of a polymerase or reverse transcriptase active buffer within a temperature range where the polymerase or reverse transcriptase is active.
Preferably, the Ago protein and/or PIWI domain-containing protein forms a binary complex with the primer that can trigger the polymerization activity of a polymerase or reverse transcriptase.
Preferably, the Ago protein and/or PIWI domain-containing protein is a protein capable of binding primers greater than 24nt in length.
In the present invention, the expressions Ago protein, argonaute nuclease are used interchangeably and refer to the same meaning and include naturally occurring or engineered proteins.
Wherein the Argonaute protein is one or more selected from sequences shown in SEQ ID NO. 1-93; and one or more amino acid sequences selected from the group consisting of amino acid sequences having at least 50% sequence homology to the sequences shown in SEQ ID NOS.1-93.
In specific embodiments, the Argonaute protein comprises an amino acid sequence having at least about 50% sequence homology (such as at least about 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or more) to a sequence selected from SEQ ID No. 1-93.
In specific embodiments, the Argonaute protein comprises an amino acid sequence having at least about 50% sequence homology (such as at least about 50%, at least 51%, at least 52%, at least 53%, at least 54%, at least 55%, at least 56%, at least 57%, at least 58%, at least 59%, at least 60%, at least 61%, at least 62%, at least 63%, at least 64%, at least 65%, at least 66%, at least 67%, at least 68%, at least 69%, at least 70%, at least 71%, at least 72%, at least 73%, at least 74%, at least 75%, at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% above) to a sequence selected from SEQ ID No. 1.
Preferably, the Argonaute protein is one or more of NgAgo, maAgo, hpAgo, naAgo, ntAgo, npAgo, hbAgo, tbAgo, teAgo, hlAgo, miAgo, syAgo, cpAgo, ibAgo, fpAgo, haAgo, mfAgo, plAgo, tcAgo, aaAgo, ssAgo, toAgo, mkAgo, seAgo, scAgo, afAgo, exAgo, lyAgo, sjAgo, cbAgo, hkAgo, baAgo, bgAgo, hmAgo, mlAgo, phAgo, rbAgo, mpAgo, kmAgo, blAgo, capAgo, calAgo, cbtAgo, cdAgo, ciAgo, csAgo, csdAgo, clcAgo, cloAgo, dlAgo, euAgo, prAgo, pxAgo, bwAgo, bcAgo, cbjAgo, gtAgo, keAgo, kpAgo, lsAgo, lbAgo, marAgo, poAgo, paAgo, phpAgo, roAgo, tmAgo, thAgo, tvAgo, tbcAgo, tdAgo, bfAgo, beAgo, brAgo, coAgo, deAgo, pmAgo, pbAgo, rsAgo, mbpAgo, halaAgo, halAgo, hrAgo, hvAgo, abAgo, amAgo, atAgo, abbAgo, adAgo, dbAgo, ppAgo, ttAgo, rsAgo.
In some embodiments, the Argonaute protein is one or more selected from MlAgo, calAgo, dmCalAgo, afAgo, hlAgo, marAgo, poAgo, roAgo, gtAgo, beAgo, brAgo, coAgo, tbcAgo, ssAgo, dlAgo, kpAgo, tcAgo, thAgo, bwAgo and the like. More specifically, the Argonaute protein is MlAgo, calAgo, dmCalAgo.
The Argonaute proteins are derived from one or more organisms including, but not limited to, organisms selected from the list set forth in table a below. The Argonaute proteins include, but are not limited to, one or more of the proteins listed in table a below. The corresponding protein sequence is one or more of SEQ ID NO. 1-93.
Table A
In the present invention, the polymerase is a polymerase that is active under temperature conditions that simultaneously keep the Ago protein and/or PIWI domain-containing protein active.
In the present invention, the polymerase is selected from DNA polymerases that are not inactivated by tolerance to high temperatures of 95 ℃ and/or DNA polymerases that are not tolerant to >80 ℃;
wherein, the DNA polymerase which is not inactivated and can resist the high temperature of 95 ℃ comprises high temperature resistant DNA polymerase and high temperature resistant DNA strand displacement polymerase, and is selected from one or more of the following:
high temperature resistant DNA polymerase: including but not limited to Taq, phanta, one Taq, la Taq, etc.;
High temperature resistant DNA strand displacement polymerase: including but not limited to SD-Taq, vent, etc.
Wherein the intolerant DNA polymerase with the temperature of 80 ℃ comprises 65 ℃ DNA polymerase, 37 ℃ DNA polymerase and 30 ℃ DNA polymerase, which are selected from one or more of the following:
65℃DNA polymerase: including but not limited to Bst DNAPolymerase, bst2.0 DNAPolymerase, bst 3.0.0 DNAPolymerase, etc.;
37 ℃ DNA polymerase: including but not limited to Bsu DNAPolymerase, etc.;
DNA polymerase at 30 ℃): including but not limited to phi29 DNAPolymerase and the like.
Preferably, the Argonaute protein and/or PIWI domain-containing protein is present and functions in the nucleic acid polymerization reaction of the invention simultaneously with the polymerase.
In the present invention, the primer serves as both a primer for targeted binding to a template in a PCR nucleic acid polymerase reaction and as a guide for the Ago protein and/or PIWI domain-containing protein, such as gDNA or gRNA.
In some embodiments, suitable primers of the invention are determined under the precondition of maintaining the polymerase active. For example, the length range of the primer and the GC content range of the primer are selected and determined under the condition that the activity of the polymerase in the reaction is ensured (more preferably, the polymerase has high activity). More preferably, the defined primers are chosen such that the Ago protein and/or the PIWI domain containing protein reacts with the polymerase with optimal activity.
The primer is a guide strand. In some embodiments, the Argonaute protein and/or PIWI domain-containing protein under its guidance increases the speed and efficiency of the rapid specific targeting to bind to the complementary sequence of the template. In some embodiments, the primer is a guide DNA, gDNA. Including but not limited to guide DNA as an Argonaute protein and/or PIWI domain-containing protein. Preferably, the primers allow for optimal activity of both the Argonaute (Ago) protein and/or PIWI domain-containing protein and polymerase to participate in the reaction.
Preferably, the length of the primer is 24 nt-80 nt; preferably, the primer length is greater than 30nt, preferably, 30nt-60nt. In some embodiments, preferably, the primer length is 25nt, 30nt, 35nt, 40nt, 45nt, 50nt, 55nt, 60nt, or others.
The GC content of the primer ranges, for example, the GC content of the primer is 10% -50%; the GC content of the primer is less than 30%, preferably 10% -30%. In some embodiments, preferably, the primer GC content is 15%,20%,25%,30%,35%,40%,50% or others.
In the present invention, the primer is phosphorylated at the 5' end.
Preferably, the sequence of the primer is one or more of SEQ ID NO. 94-95, 97-102, 104-114 and 116-156.
The template is nucleic acid, DNA or RNA. Preferably ssDNA, RNA. Including template nucleic acids, nucleic acids to be amplified, nucleic acids to be tested, and the like. The template contains a sequence complementary to the primer. In a specific embodiment, the template is M13mp18 single stranded circularized DNA. Preferably, the Argonaute protein and/or PIWI domain-containing protein forms a binary complex with a primer that specifically recognizes and targets binding to a template to be amplified, which contains a sequence complementary to the primer.
The template, template to be amplified, nucleic acid to be tested include, but are not limited to, isolated DNA, RNA, including any DNA, RNA to be amplified, including any source, natural or genetically engineered, DNA, RNA of any length. Preferably, the Argonaute protein and/or PIWI domain-containing protein is capable of binding to a guide RNA or a single stranded guide DNA specifically targeted to a target sequence complementary to the guide sequence. In some embodiments, the Argonaute protein and/or PIWI domain-containing protein comprises an Argonaute protein and/or PIWI domain-containing protein with or without cleavage capability. Argonaute proteins and/or PIWI domain-containing proteins that are in the absence of cleavage or in a weak cleavage capacity under the circumstances of the practice of the present invention. Or it may be an Argonaute protein and/or a PIWI domain-containing protein having cleavage ability, which is related to the ability of the corresponding polymerase. In some embodiments, the Argonaute protein and/or PIWI domain-containing protein functions as an annealing promoting enzyme in the nucleic acid polymerase chain reaction (PCR reaction), having the function of a PCR reaction annealing promoting enzyme. In some embodiments, the Argonaute protein and/or PIWI domain-containing protein promotes M13mp18 double-stranded, using both 5'P and 5' oh primers is effective, and phosphorylating the primer faster and more efficient.
Furthermore, the Argonaute protein and the nucleic acid polymerase exist in a reaction system at the same time and have activity, the Argonaute protein and the primer are quickly and specifically bound with the template, dNTP is used as a raw material under the action of the polymerase, and the nucleic acid polymerase is reacted according to a base complementary pairing principle and a semi-reserved replication principle to synthesize the complementary strand of the template.
In the present invention, the reverse transcriptase is selected from one or more of Bst3.0 DNAPolymerase, thermostable RTase, AMV RTase, M-MLVRtase.
The invention also provides a PCR amplification nucleic acid method involving Argonaute protein, which uses single-stranded DNA or RNA as a template, forms a binary complex based on Ago protein (Argonaute protein) and a primer, forms a binary complex with Argonaute (Ago) protein and the primer, rapidly and specifically targets the complementary sequence of the binding template, uses dNTP as a reaction raw material under the action of polymerase or reverse transcriptase, and uses single-stranded DNA or RNA as the template to perform Ago-PCR nucleic acid amplification reaction. Wherein the Argonaute protein simultaneously acts as an annealing promoting enzyme in said nucleic acid polymerase chain reaction.
In some embodiments, the reverse transcriptase is selected from one or more of Bst3.0 DNA Polymerase, thermostable RTase, AMVRTase, M-MLVRtase.
The method of the invention is carried out at a temperature that maintains the activity (preferably, high activity) of both the PIWI domain-containing protein and the polymerase. Preferably, the PIWI domain-containing protein is an Argonaute protein. In specific embodiments, the Ago-primer binary complex binds to the template with high efficiency targeting.
The PCR nucleic acid amplification method of Argonaute protein and/or PIWI domain-containing protein includes, but is not limited to, ago and/or PIWI domain-containing protein-PCR isothermal amplification, ago and/or PIWI domain-containing protein-PCR variable temperature amplification, ago and/or PIWI domain-containing protein-RT-PCR amplification and the like.
In particular embodiments, the reaction may be performed at variable temperatures, i.e., a variable temperature PCR nucleic acid amplification reaction involving an Argonaute protein and/or a PIWI domain-containing protein. Wherein, when the temperature is variable, the variable temperature comprises a first temperature and a second temperature. The first temperature is a temperature capable of sufficiently opening a double-stranded template while not affecting the Ago protein-based and/or PIWI domain-containing protein activity, polymerase activity; opening the DNA duplex and maintaining the activity of the Ago protein and/or PIWI domain-containing protein, the activity of the polymerase, and the Ago protein and/or PIWI domain-containing protein and the primer are rapidly and specifically targeted to the binding template at the first temperature. The second temperature is a temperature at which polymerase activity is maintained; and under the action of DNA polymerase, performing nucleic acid polymerase chain reaction by taking dNTPs as reaction raw materials at the second temperature.
The invention of Ago and/or containing PIWI domain protein-PCR variable temperature amplification nucleic acid method, the method includes the following steps: opening the DNA double strand at a first temperature, then forming a binary complex by taking single-strand DNA as a template, argonaute protein and/or PIWI domain-containing protein and a primer to quickly and specifically target the complementary sequence of the binding template, and amplifying under the action of DNA polymerase at a second temperature.
The template DNA single strand comprises a sequence complementary to the primer.
The Argonaute protein and/or the PIWI domain-containing protein is a complementary sequence of the Argonaute protein and/or the PIWI domain-containing protein which can keep high activity at a first temperature, namely, the Argonaute protein and/or the PIWI domain-containing protein and a primer form a binary complex to quickly and specifically target a binding template. The Argonaute proteins include, but are not limited to, one or more of those listed in table a. More preferably, the Argonaute protein is MlAgo, calAgo, dmCalAgo, calAgo, afAgo, hlAgo, marAgo, poAgo, roAgo, gtAgo, beAgo, brAgo, coAgo, tbcAgo, ssAgo, dlAgo, kpAgo, tcAgo, thAgo, bwAgo.
Preferably, the Argonaute protein comprises an amino acid sequence having at least about 40% sequence homology to a sequence selected from SEQ ID nos. 1-93. Preferably, it comprises an amino acid sequence having at least about 40% sequence homology with the sequence of SEQ ID NO. 35.
In particular embodiments, the double stranded template is capable of being sufficiently opened at the first temperature without affecting the activity of the Argonaute protein and/or PIWI domain containing protein and polymerase; at the second temperature corresponds to the optimum temperature for polymerase activity.
Preferably, the first temperature is a temperature that is capable of opening a double stranded template while not affecting the activity of the Argonaute protein and/or PIWI domain containing protein and polymerase activity. The first temperature means that the double stranded template can be sufficiently opened at that temperature without any negative effect of reducing or inhibiting or down-regulating the high activity of the Argonaute protein and/or PIWI domain containing protein and the high activity of the polymerase. More preferably, the first temperature is 80 ℃ to 100 ℃. More preferably, the first temperature is 82 ℃.
Preferably, the second temperature is any temperature that helps to maintain high activity of the polymerase. More preferably, the second temperature is 30 ℃ to 75 ℃. More preferably, the second temperature is 68 ℃.
In some embodiments, the reaction may be performed at a constant temperature, i.e., a isothermal PCR nucleic acid amplification reaction involving Argonaute proteins and/or PIWI domain-containing proteins. Wherein, at constant temperature, the method comprises the following steps: at constant temperature, double-stranded DNA is opened under the action of helicase, the Argonaute protein and/or the PIWI domain-containing protein and the primer form a binary complex to rapidly and specifically target the complementary sequence of a binding template, and single-stranded DNA is used as the template for amplification under the action of DNA polymerase. Wherein the helicase is one that is capable of opening double stranded template DNA at a constant temperature while maintaining the activity of the Argonaute protein and/or PIWI domain containing protein and polymerase. Preferably the helicase is selected from one or more of the group including, but not limited to, ec Uvrd helicase, tte Uvrd helicase, T7gp4B helicase, and the like.
The isothermal amplification method can be performed at any temperature that enables the Argonaute protein and/or PIWI domain-containing protein involved in the reaction to reach high activity and enables the polymerase involved in the reaction to remain high activity, and Ago and/or PIWI domain-containing protein-primers target sequences with high efficiency. The temperature may be any temperature. Preferably, the constant temperature is 30-70 ℃; more preferably, the constant temperature is 65 ℃.
In the Ago and/or PIWI domain-containing protein-PCR isothermal nucleic acid amplification method of the present invention, the Argonaute proteins include, but are not limited to, one or more of the proteins listed in table a. More preferably, the Argonaute protein is CalAgo, marAgo, poAgo, ssAgo, dlAgo, kpAgo, tcAgo, thAgo, bwAgo. Preferably, the Argonaute protein includes, but is not limited to, one or more of the sequences shown as SEQ ID NO. 1-93. Preferably, the Argonaute protein comprises at least about 50% sequence homology to a sequence selected from the group consisting of SEQ ID NO. 1-93. Preferably, it comprises an amino acid sequence having at least about 50% sequence homology with the sequence of SEQ ID NO. 42.
In a specific embodiment, the sequences of the primers are shown as SEQ ID NO.94-95, 97-102, 104-114 and 116-156.
Further, the present invention provides a method for amplifying nucleic acid by Ago and/or PIWI domain-containing protein-RT-PCR, comprising the steps of:
(1) Taking RNA as a template, forming a binary complex by Argonaute (Ago) protein and/or PIWI structural domain-containing protein and a primer, rapidly and specifically targeting and combining the template RNA, and synthesizing first-strand cDNA under the action of reverse transcriptase;
(2) The first strand cDNA is used as a template, argonaute (Ago) protein and a primer form a binary complex, the cDNA template is combined in a rapid specific targeting way, and then the PCR amplification is carried out by the nucleic acid polymerase chain reaction under the action of DNA polymerase.
Preferably, the reverse transcriptase is selected from the group consisting of 60 ℃ reverse transcriptase, 30 ℃ reverse transcriptase, including but not limited to one or more of the following:
reverse transcriptase at 60 ℃): bst3.0 DNAPolymerase, thermostable RTase, etc.;
reverse transcriptase at 30 ℃): AMVRTase, M-MLVRTase, etc.
Preferably, the reverse transcriptase is selected from one or more of the group consisting of, but not limited to, ec Uvrd helicase, tte Uvrd helicase, T7gp4B helicase, and the like.
Preferably, the Argonaute proteins include, but are not limited to, one or more of those listed in table a. More preferably, the Argonaute protein is dmMbpAgo, mlAgo.
In a specific embodiment, the sequences of the primers are shown as SEQ ID NO.94-95, 97-102, 104-114 and 116-156.
Further, the present invention provides a method for amplifying a tube of multi-site Ago and/or PIWI domain-containing protein-PCR nucleic acid, comprising the steps of:
the method comprises the steps of taking single-stranded DNA or RNA as a template, forming a binary complex by Argonaute protein and/or PIWI structural domain-containing protein and a primer, quickly and specifically combining the complementary sequence of the template, and then carrying out nucleic acid amplification, namely nucleic acid polymerase chain reaction, by taking dNTPs as reaction raw materials under the action of polymerase or reverse transcriptase.
The method for amplifying the protein-PCR nucleic acid of the multi-site Ago and/or the PIWI domain in one tube comprises a method for amplifying the temperature-changing nucleic acid of the protein-PCR of the multi-site Ago and/or the PIWI domain in one tube, a method for amplifying the constant temperature nucleic acid of the protein-PCR of the multi-site Ago and/or the PIWI domain in one tube, and a method for amplifying the nucleic acid of the protein-RT-PCR of the multi-site Ago and/or the PIWI domain in one tube. Argonaute protein and/or PIWI domain containing protein, primer, polymerase, reverse transcriptase, etc. are equivalent to the foregoing.
The invention also provides a nucleic acid polymerase reaction system based on Ago proteins and/or PIWI domain-containing proteins, comprising: ago proteins and/or PIWI domain-containing proteins, and polymerases.
Wherein the polymerase exists in the reaction system together with the Ago protein and/or the PIWI domain-containing protein, and realizes nucleic acid polymerase reaction under the action of enzymatic reaction.
Preferably, the Ago protein and/or the PIWI domain-containing protein is active and the polymerase is active. More preferably, the Ago protein and/or the PIWI domain-containing protein has a high activity and the polymerase has a high activity.
Further, the system also includes a primer. Preferably, the primer directs and simultaneously specifically targets the Ago protein and/or PIWI domain-containing protein to the template and serves as a primer in a PCR reaction system. Preferably, the primer reacts the Ago protein and/or PIWI domain-containing protein with the polymerase with optimal activity.
Preferably, templates, primers, polymerase, ago proteins and/or PIWI domain-containing proteins are included in the system.
Wherein the Ago protein and/or the PIWI domain-containing protein is a protein that promotes or enhances the complementary binding of the primer to the template.
The invention also provides an Ago protein and/or a binary complex of a protein containing a PIWI domain and a primer, preferably, the binary complex consists of the Ago protein and/or the protein containing the PIWI domain or a nucleic acid encoding the protein containing the PIWI domain and the primer, namely, the Ago protein and/or the protein-primer binary complex containing the PIWI domain, which can specifically recognize and target the template nucleic acid, the nucleic acid to be detected and the template to be amplified which contain the sequence complementary to the primer, and can trigger the polymerization activity of polymerase or reverse transcriptase, and the sequence of the nucleic acid to be detected and the template to be amplified contains the sequence complementary to the primer. Preferably, the present invention provides a binary complex comprising an Argonaute protein and a primer. More preferably, the binary complex is composed of Argonaute protein and a primer, namely, an Ago-primer binary complex, and the binary complex can specifically identify and target and bind to a nucleic acid to be amplified and a template to be amplified, wherein the sequences of the nucleic acid to be detected and the template to be amplified contain sequences complementary to the primer.
In some embodiments, the binary complex may also be a nucleic acid comprising a primer and encoding the Argonaute protein. In some embodiments, the primer may be a guide DNA. The Argonaute protein comprises at least 40% sequence homology with a sequence shown in SEQ ID NO. 1-93; preferably the Argonaute protein is one or more of the sequences shown as SEQ ID NO. 1-93; preferably SEQ ID No. 35. The Argonaute protein source is selected from one or more of table a.
The invention also provides a composition or a reagent or a kit, which comprises the nucleic acid polymerase reaction system based on the Ago protein and/or the PIWI domain-containing protein, and/or comprises the Ago protein and/or the PIWI domain-containing protein-primer binary complex. Preferably it comprises the binary complex formed by the Argonaute protein (and possibly also the nucleic acid encoding the Argonaute protein) and/or the PIWI domain-containing protein and a primer, which is capable of specifically targeting the template or nucleic acid to be amplified; the template to be amplified or the target nucleic acid to be detected contains a sequence complementary to the primer. The composition or the reagent or the kit can be used in a PCR reaction system.
The invention also provides a PCR nucleic acid amplification reaction system based on Ago protein and/or PIWI domain-containing protein (including Argonaute protein), which comprises a binary complex formed by Argonaute protein and/or PIWI domain-containing protein and a primer and capable of specifically and targeted binding with a template to be amplified or nucleic acid to be detected; the template to be amplified or the target nucleic acid to be detected contains a sequence complementary to the primer.
The invention also provides an application, namely the Ago protein and/or the PIWI domain-containing protein, a nucleic acid polymerase reaction system based on the Ago protein and/or the PIWI domain-containing protein, an Argonaute protein and primer binary complex of the Ago protein and/or the PIWI domain-containing protein, a PCR nucleic acid amplification reaction system participated by the Argonaute protein and/or the PIWI domain-containing protein, an application of a composition or a reagent or a kit of the PIWI domain-containing protein/Argonaute protein and the like in PCR nucleic acid amplification reaction.
The invention also provides application of the Ago protein and/or the PIWI structural domain-containing protein and the polymerase in a PCR nucleic acid amplification reaction system simultaneously and actively.
In the prior art, the Ago detection nucleic acid technology utilizes the cutting capability of Ago, such as the A-STAR: A-STAR technology, or relies on traditional PCR, and the high-temperature Ago is utilized to cut off the non-specific template and only retain the specific template, so that the detection limit and the amplification efficiency of the PCR are not improved. Or, RADAR: the RADAR technology uses high-temperature Ago as a final detector for detecting the products of the traditional PCR, which is equivalent to agarose gel detection, and does not improve the detection limit and amplification efficiency of the PCR.
In the Ago-PCR method provided by the invention, ago is used as an annealing promoting enzyme instead of a cutting enzyme. The Argonaute combined gDNA targeting target is an enzymatic reaction, so that the matching speed and probability of the primer and the template can be improved. The Ago-PCR variable-temperature amplification of the invention is to increase argonaute to promote the matching of the primer and the template on the basis of the traditional PCR, does not need an annealing program, reduces the reaction time, improves the detection limit and the amplification efficiency of the traditional PCR, and does not increase the cost. The Ago-PCR isothermal amplification method can amplify nucleic acid at constant temperature with high efficiency, and does not need expensive temperature changing equipment; the argonaute with high activity at different temperatures is selected through screening, the high activity of the polymerase is kept, and the argonaute can be amplified at constant temperature at any temperature; the components are simple, and SSB protein is not needed; the product length can be amplified efficiently from 200 to 5000 bp; the product can be used for sequencing; the Ago-primer binary complex can target the target efficiently at the temperature which can keep the high activity of Ago protein Argonaute protein and the high activity of polymerase, so that the annealing temperature of the primer is not considered; the primer consumption is reduced; multiple sites can be detected simultaneously in a tube system.
The beneficial effects of the invention include: argonaute and/or PIWI domain-containing protein binding gDNA targeting target is an enzymatic reaction, and can improve the matching speed and probability of a primer and a template, thereby improving the detection limit and amplification efficiency of PCR. The sensitivity is high, and trace target nucleic acid can be detected in the mixed template. The flexibility is strong, and can not only identify the DNA template, but also identify the RNA template. Can be reacted at a higher temperature or at normal temperature. The method is suitable for both temperature-variable amplification and isothermal amplification. The method is not limited by primer annealing temperature, can amplify at different temperatures, has Argonaute in various living environments, and can easily screen Argonaute with high activity at different temperatures. The primer consumption is reduced, the detection time is shortened, various detection means on the market can be used for detecting the product, and the product can be used for sequencing.
Drawings
FIG. 1 is a schematic diagram of an Ago-PCR model. Ago-PCR has two basic reaction steps: (1) template DNA opens double strand binding to Ago-gDNA: opening double chains of the template DNA under the action of high temperature or helicase, and rapidly and specifically targeting and combining the complementary sequences of the single chains of the template DNA by the Ago-gDNA; (2) primer extension: under the action of DNA polymerase, the DNA template-gDNA conjugate uses dNTP as reaction raw material, target sequence as template, and according to the base complementary pairing and semi-reserved replication principle, a new semi-reserved replication chain complementary with template DNA chain is synthesized, and the two processes of repeated circulation can obtain more 'semi-reserved replication chains', and said new chain can be used as template for next circulation.
FIG. 2 is a schematic of Ago-PCR temperature swing amplification.
FIG. 3 shows the result of detecting the Ago-PCR variable temperature amplified nucleic acid by the qPCR instrument.
FIG. 4 shows the result of detecting the Ago-PCR temperature change amplified nucleic acid by a blue light instrument.
FIG. 5 shows the result of agarose gel detection Ago-PCR temperature change amplification of nucleic acid.
FIG. 6 shows the comparison of Ago-PCR temperature swing amplification with conventional PCR, agarose gel detection.
FIG. 7 shows that the qPCR instrument detects the Ago-PCR variable-temperature amplification to detect the single copy target template in the mixed template.
FIG. 8 is a graph showing the relationship between Ct value and sample concentration.
FIG. 9 shows that the blue light instrument detects the Ago-PCR variable-temperature amplification to detect the single copy target template in the mixed template.
FIG. 10 shows that primers of different lengths can be used for detecting Ago-PCR temperature-variable amplification by a qPCR instrument.
FIG. 11 shows that primers of different lengths can be used for detecting the Ago-PCR variable-temperature amplification by a blue-ray instrument.
FIG. 12 shows that the Ago-PCR temperature change amplification can be detected by using primers with different lengths and agarose gel.
FIG. 13 shows that different templates can be used for qPCR instrument detection Ago-PCR temperature-variable amplification.
FIG. 14 shows that different templates can be used for detecting Ago-PCR temperature-variable amplification by a blue-ray instrument.
FIG. 15 shows that different templates, agarose gel detection, can be used for Ago-PCR temperature change amplification.
FIG. 16 shows that various Ago can perform Ago-PCR temperature change amplification and agarose gel detection.
FIG. 17 is a schematic of the isothermal amplification of Ago-PCR.
FIG. 18 shows the result of agarose gel detection Ago-PCR isothermal amplification.
FIG. 19 shows the result of agarose gel detection Ago-PCR isothermal amplification.
FIG. 20 shows agarose gel detection Ago-PCR isothermal amplification one-tube multi-site amplification.
FIG. 21 shows agarose gel detection Ago-PCR isothermal amplification one-tube multi-site amplification.
FIG. 22 shows that various Ago can be subjected to Ago-PCR isothermal amplification, and agarose gel detection.
FIG. 23 is a schematic representation of an experiment for Ago protein promotion of M13mp18 duplex.
FIG. 24 shows the results of agarose gel detection of M13mp18 duplex.
FIG. 25 shows the rate and efficiency of the qPCR instrument to detect that the Ago protein promotes M13mp18 duplex.
FIG. 26 shows the speed and efficiency of qPCR apparatus to detect different primer lengths Ago proteins to promote M13mp18 duplex.
FIG. 27 shows the rate and efficiency of the Ago protein to promote M13mp18 duplex by qPCR assay 5'P primer and 5' OH primer.
FIG. 28 is a schematic of the Ago-RT-PCR process.
FIG. 29 shows qPCR apparatus for detecting Ago-RT-PCR high temperature variable temperature amplification.
FIG. 30 shows the results of agarose gel detection Ago-RT-PCR.
FIG. 31 shows PIWI domain-containing proteins.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples and drawings. The procedures, conditions, experimental methods, etc. for carrying out the present invention are common knowledge and common knowledge in the art, except for the following specific references, and the present invention is not particularly limited.
EXAMPLE 1Ago-PCR temperature-variable amplification of nucleic acids
The template DNA opens double chain at the first temperature of 82 ℃ for 1min, then Argonaute (Ago) protein and primer are fast and specifically bound with the complementary sequence of the template DNA single chain, then dNTP is used as a reaction raw material under the action of DNA polymerase, the target sequence is used as a template, according to the base complementary pairing and half-reserved replication principle, extension is carried out at the second temperature of 68 ℃ for 30s, a new half-reserved replication chain complementary with the template DNA chain is synthesized, then the two processes are repeated, more half-reserved replication chains can be obtained, and the new chain can become the template of the next circulation.
Table 1 shows the experimental details and procedure of this example
In this example, the Ago protein was MlAgo protein and the template was M13mp18 single stranded circularized DNA.
The primers used were as follows:
primer 1:
oM13-3 5'-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.94)
primer 2:
oM13-25 5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTTGGTACAACCG-3'(SEQ ID NO.95)
taqman probes:
F-M13-25'FAM-CGCGAGCTGAAAAGGTGGCATCAATTC-3'BHQ1(SEQ ID NO.96)
the specific experimental steps are as follows:
1-1) Ago protein was incubated with the primers in advance.
Into the PCR tube of the experimental group, 1.5ul of 1uM concentration upstream and downstream primers (oM-3, oM-25), 2ul 5X Amplification Buffer (1 XBuffer component: 20mM Tris-HCl;10mM (NH 4)) were added 2 SO 4 ；50mM KCl；4mM MgSO4；0.1％20, a step of; pH 8.8), 0.1ul BSA at a concentration of 20ug/ul, 1ul MlAgo at a concentration of 1ug/ul, add ddH2O to the total system of 10ul and incubate at 55℃for 15min.
1-2) Ago-PCR temperature-variable amplification system.
When the incubation of the product is waited, a new fluorescent quantitative special PCR tube is used for preparing an amplification system, 1ul of single-chain M13mp18 template with the concentration of 2.5pg/ul and 0.5ul 10mM dNTP Mixture,4ul 5XAmplification Buffer,0.5ul 10uM probe F-M13-2 are added into the PCR tube, after the incubation process is finished, 0.5ul of 5U/ul Taq DNA Polymerase polymerase is added into the amplification system, ddH2O is added to 20ul of the whole system, and 10ul of mineral oil is added for sealing after all the incubation products are put into the amplification system and mixed uniformly.
1-3) Ago-PCR amplification procedure with a fluorescent quantitative PCR apparatus (BIO-RAD CFX-96)
The following procedure was run:
182℃，1min；
shooting at 268 ℃ for 30 s;
3 Go to 1, 50 cycles
2-1) detection by a fluorescent quantitative PCR instrument (BIO-RAD CFX-96) can directly obtain fluorescent quantitative data. As shown in the fluorescence data of FIG. 3, the fluorescence signal value of the whole reaction process of the No. 1 non-M13 mp18 template group and the No. 2 non-MlAgo group is 0, the fluorescence is generated in the No. 3 experimental group, the ct value is 24, the reaction is carried out for 50 cycles, the fluorescence signal reaches the highest and tends to be stable, and 7000RFU is more.
2-2) samples from which the program run was completed were observed under a blue light instrument as in FIG. 4, no. 1 without M13mp18 template, and No. 2 without MlAgo two negative controls were not visibly clear green, while No. 3 experimental had visibly clear green.
2-3) samples from which the program run was completed were run using an EB-containing 1% agarose gel for electrophoresis detection as in FIG. 5, no M13mp18 template group was added to No. 1, and no MlAgo group was added to No. 2 two negative controls with no specific bands, only no test group with the target bands.
Example 2 comparison of Ago-PCR temperature Change amplification of the invention with conventional PCR
The specific system and reaction procedure for Ago-PCR temperature swing amplification in example 2 of the present invention are shown in Table 2 below. Other procedures and conditions of the experimental procedure are described in example 1 of the present invention.
TABLE 2
In this example, the Ago protein is the MlAgo protein, the template is M13mp18 single-stranded circularized DNA,
the primers used in this example are as follows:
primer 1:
oM13-3 5'-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.97)
primer 2:
oM13-25 5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTTGGTACAACCG-3'(SEQ ID NO.98)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH 8.8
Traditional PCR method:
table 3 shows the conventional PCR system and reaction procedure.
TABLE 3 Table 3
In the traditional PCR reaction, the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
primer 1:
oM13-3-40 5'-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATT-3'(SEQ ID NO.99)
primer 2:
oM13-25-30 5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCA-3'(SEQ ID NO.100)
template M13mp18 at different concentrations: 10ul of M13mp18 template at 25pg/ul (6X 106 copies/ul) was diluted to a concentration of 2.5pg/ul (6X 105 copies/ul) with 90ul ddH 2O; then 10ul of M13mp18 template with the concentration of 2.5pg/ul (6X 105 copies/ul) is taken, 90ul of ddH2O is added, and the mixture is diluted to the M13mp18 template with the concentration of 250fg/ul (6X 104 copies/ul); stepwise dilution was performed in the same manner until the template was diluted to 6copies/ul.
Comparison of results:
table 4 shows a comparison of Ago-PCR temperature swing amplification with conventional PCR procedure and time
As shown in FIG. 6, the temperature-variable amplification of the Ago-PCR can detect 6 copies/30 microlitres, and the traditional PCR can only detect 600 copies/30 microlitres; and at the same concentration, the temperature-variable amplification efficiency of the Ago-PCR is higher than that of the traditional PCR; in addition, the Ago-PCR temperature-changing amplification method is shorter.
Example 3 Ago-PCR temperature-variable amplification detection of Trace amount of templates of interest in hybrid templates
The specific system and reaction procedure for Ago-PCR temperature swing amplification in example 3 of the present invention are shown in Table 5 below. Other procedures and conditions of the experimental procedure are described in example 1 of the present invention.
TABLE 5
In this example, the Ago protein is the MlAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
primer 1:
oM13-3
5'-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.101)
primer 2:
oM13-25
5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTTGGTACAACCG-3'(SEQ ID NO.102)
taqman probes:
F-M13-2 5'FAM-CGCGAGCTGAAAAGGTGGCATCAATTC-3'BHQ1(SEQ ID NO.103)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH 8.8
Hybrid template processing: taking 50ul of M13 template with a concentration of 250pg/ul (6X 107 copies/ul), adding 50ul of 293T cell genome with a concentration of 275ng/ul, and obtaining a hybrid template with 3X106 copies M13 and 137.5ng 293T cell genome per microliter; similarly, 50ul of M13 template at 250pg/ul (6X 106 copies/ul) was added to 50ul of 293T cell genome at 275ng/ul to obtain a mixed template having 3X105 copies M13 and 137.5ng 293T cell genome per ul, and the mixed template was prepared in the same manner until a mixed template having 3copies M13 and 137.5ng 293T cell genome per ul was obtained, and 2ul was used as the template for amplification at the time of the preparation.
Detecting M13 phage genome standard samples of the hybrid 293T cell genome on a real-time fluorescent quantitative PCR instrument by using the Ago-PCR method of the invention to obtain an amplification curve (FIG. 7) and a standard curve (FIG. 7), wherein the different curves shown in FIG. 7 respectively represent the amplification of different M13 template concentrations, 1) no template, 2) 6x106copies, 3) 6x105copies, 4) 6x104copies, 5) 6000copies, 6) 600copies, 7) 60copies, 8) 6copies; shown in FIG. 8 is the relationship between Ct value and sample concentration, resulting in an amplification efficiency of 98.5%. Fig. 9 shows an experimental sample, which was observed under a blue light meter, and the experimental group (No. 2 to 8) was seen to have green light with the green light becoming weaker as the concentration of the M13 template was reduced.
Example 4 Ago-PCR temperature-variable amplification primers of different lengths can be used
The specific system and reaction procedure for Ago-PCR temperature swing amplification in example 4 of the present invention are shown in Table 6 below. Other procedures and conditions of the experimental procedure are described in example 1 of the present invention.
TABLE 6
In this example, the Ago protein is the MlAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
different length primer 1:
oM13-3-27：5'-TTAAATATGCAACTAAAGTACGGTGTC-3'(SEQ ID NO.104)
oM13-3-30：5'-TTAAATATGCAACTAAAGTACGGTGTCTGG-3'(SEQ ID NO.105)
oM13-3-40：5'-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATT-3'(SEQ ID NO.106)
oM13-3-50：
5'-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.107)
different length primer 2:
oM13-25-27：5'-GGCTTCTCCCGCAAAAGTATTACAGGG-3'(SEQ ID NO.108)
oM13-25-30：5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCA-3'(SEQ ID NO.109)
oM13-25-40：5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTT-3'(SEQ ID NO.110)
oM13-25-50：
5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTTGGTACAACCG-3'(SEQ ID NO.111)
F-M13-2：5'FAM-CGCGAGCTGAAAAGGTGGCATCAATTC-3'BHQ1(SEQ ID NO.112)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1% 20；pH8.8
As shown in the fluorescence data of FIG. 10, the amplification fluorescence data of the primers with the numbers of 1-4 being 27nt, 30nt, 40nt and 50nt respectively show that the amplification signal is strongest when the primer length is between 27nt and 50nt, and the amplification of the primer with the length of 50nt can be realized by relying on MlAgo with the height of Wen Bianwen; observing the detected sample under a blue light instrument, as shown in fig. 11, the macroscopic numbers 1-4 have green light, and the macroscopic number 4 is the strongest; electrophoresis was performed using an EB-containing 1% agarose gel, as shown in FIGS. 12, with the target bands of product size for all numbers 1-4, with the maximum amplification for number 4.
Example 5 Ago-PCR temperature-variable amplification different templates can be detected
The specific system and reaction procedure for Ago-PCR temperature swing amplification in this example 5 is shown in Table 7 below. Other procedures and conditions of the experimental procedure are described in example 1 of the present invention.
TABLE 7
In the embodiment, the Ago protein is MlAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
primer 1:
oM13-3-50：
5’-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3’(SEQ ID NO.113)
primer 2:
oM13-25-50：
5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTTGGTACAACCG-3'(SEQ ID NO.114)
taq man probe F-M13-2:5'FAM-CGCGAGCTGAAAAGGTGGCATCAATTC-3' BHQ1 (SEQ ID NO. 115)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
Different templates:
no. 2: double-stranded PCR fragment with concentration of 104copies/ul 1300bp
No. 3: single-chain circular M13mp18 with concentration of 104copies/ul
No. 4: plasmid template with concentration of 104copies/ul
As shown in the fluorescence data of FIG. 13, the no-template group No. 1 has fluorescence signals of 0,2-4, and different templates are amplified by the Ago-PCR at variable temperature; observing the detected sample under a blue light instrument, as shown in fig. 14, the different template groups of No. 2-4 are visible to the naked eye to have green light; electrophoresis was performed using an EB-containing 1% agarose gel, and the product-sized bands of interest were shown in FIGS. 15, 2-4.
EXAMPLE 6 various Ago can be subjected to Ago-PCR temperature-variable amplification
Table 8 shows the specific system and reaction procedure for Ago-PCR temperature-changing amplification
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The primers used in this example are as follows:
primer 1:
oM13-3-50：
5’-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3’(SEQ ID NO.116)
primer 2:
oM13-25-50：
5'-GGCTTCTCCCGCAAAAGTATTACAGGGTCATAATGTTTTTGGTACAACCG-3'(SEQ ID NO.117)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in FIG. 16, various Agos such as MlAgo, afAgo, HIAgo, marAgo, dmCalAgo, poAgo, roAgo, gtAgo, beAgo, brAgo, coAgo, tbcAgo can be subjected to temperature-variable amplification.
EXAMPLE 7Ago-PCR isothermal amplification method of nucleic acids
The template DNA opens double chain under the action of helicase, then Argonaute (Ago) protein and primer are fast and specifically combined with the complementary sequence of the template DNA single chain, then under the action of DNA polymerase, dNTP is used as reaction raw material, target sequence is used as template, according to the base complementary pairing and semi-reserved replication principle, extension is carried out at 65 ℃ for 1h, a new semi-reserved replication chain complementary with the template DNA chain is synthesized, then the two processes are repeated, more 'semi-reserved replication chains' can be obtained, and the new chain can become the template for the next circulation.
Table 9 shows the specific system and reaction procedure for the isothermal amplification of Ago-PCR in this example.
TABLE 9
In the embodiment, the Ago protein is CalAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
P-oM13-3：
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.118)
P-oM13-4：
5'P-TATTAACGTTTACAATTTAAATATTTGCTTATACAATCTTCCTGTTTTTG-3'(SEQ ID NO.119)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1％20；pH8.8
FIG. 18 shows that the Ago-PCR (No. 5) of the present invention can detect nucleic acid at a constant temperature of 65 ℃.
Example 8 Ago-PCR isothermal amplification can give products of different lengths
Table 10 shows the specific system and reaction procedure for the isothermal amplification of Ago-PCR.
Table 10
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In the embodiment, the Ago protein is CalAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
primer 1:
P-oM13-3:
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.120)
different primers 2:
P-oM13-6:
5'P-TAAAAATTTTTATCCTTGCGTTGAAATAAAGGCTTCTCCCGCAAAAGTAT-3'(SEQ ID NO.121)
P-oM13-4:
5'P-TATTAACGTTTACAATTTAAATATTTGCTTATACAATCTTCCTGTTTTTG-3'(SEQ ID NO.122)
P-oM13-10:
5'P-TTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGC-3'(SEQ ID NO.123)
P-oM13-14:
5'P-TGATTATAAAAACACTTCTCAGGATTCTGGCGTACCGTTCCTGTCTAAAA-3'(SEQ ID NO.124)
P-oM13-15:
5'P-TTTATTTCTGTTTTACGTGCAAATAATTTTGATATGGTAGGTTCTAACCC-3'(SEQ ID NO.125)
P-oM13-5:
5'P-GTTATTCTCTCTGTAAAGGCTGCTATTTTCATTTTTGACGTTAAACAAAA-3'(SEQ ID NO.126)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in FIG. 19, the Ago-PCR isothermal amplification of the present invention can obtain products of different lengths, 350bp in lane 1, 675bp in lane 2, 1142bp in lane 3, 2491bp in lane 4, 3411bp in lane 5, and 4330bp in lane 6.
EXAMPLE 9Ago-PCR isothermal amplification one-tube multi-site amplification
The specific system and reaction procedure for the isothermal amplification of Ago-PCR in this example 9 is shown in Table 11 below. Other procedures and conditions of the experimental procedure, etc., refer to example 7 of the present invention.
TABLE 11
In the embodiment, the Ago protein is CalAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used in this example are as follows:
primer 1:
P-oM13-3:
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.127)
primer 2:
P-oM13-6:
5'P-TAAAAATTTTTATCCTTGCGTTGAAATAAAGGCTTCTCCCGCAAAAGTAT-3'(SEQ ID NO.128)
primer 3:
P-oM13-4:
5'P-TATTAACGTTTACAATTTAAATATTTGCTTATACAATCTTCCTGTTTTTG-3'(SEQ ID NO.129)
primer 4:
P-oM13-10:
5'P-TTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGC-3'(SEQ ID NO.130)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8/>
As shown in FIG. 20, the Ago-PCR isothermal amplification of the invention can detect three sites simultaneously in one tube, the primer 1 and the primer 2 are combined to obtain a 350bp fragment, the primer 1 and the primer 3 are combined to obtain a 675bp fragment, and the primer 1 and the primer 4 are combined to obtain a 1142bp fragment.
Example 10Ago-PCR isothermal amplification primers of different lengths can be used
The specific system and reaction procedure for the isothermal amplification of Ago-PCR in this example 10 is shown in Table 12 below. Other procedures and conditions of the experimental procedure, etc., refer to example 7 of the present invention.
Table 12
In the embodiment, the Ago protein is CalAgo protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used were as follows:
different length primer 1:
P-oM13-3-18：5'P-TTAAATATGCAACTAAAG-3'(SEQ ID NO.131)
P-oM13-3-21：5'P-TACTTTAGTTGCATATTTAAA-3'(SEQ ID NO.132)
P-oM13-3-27：5'P-TTAAATATGCAACTAAAGTACGGTGTC-3'(SEQ ID NO.133)
P-oM13-3-30：5'P-TTAAATATGCAACTAAAGTACGGTGTCTGG-3'(SEQ ID NO.134)
P-oM13-3-40：
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATT-3'(SEQ ID NO.135)
P-oM13-3-50：
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.136)
different length primer 2:
P-oM13-4-18：5'P-TATTAACGTTTACAATTT-3'(SEQ ID NO.137)
P-oM13-4-21：5'P-TATTAACGTTTACAATTTAAA-3'(SEQ ID NO.138)
P-oM13-4-27：5'P-TATTAACGTTTACAATTTAAATATTTG-3'(SEQ ID NO.139)
P-oM13-4-30：5'P-TATTAACGTTTACAATTTAAATATTTGCTT-3'(SEQ ID NO.140)
P-oM13-4-40：
5'P-TATTAACGTTTACAATTTAAATATTTGCTTATACAATCTT-3'(SEQ ID NO.141)
P-oM13-4-50：
5'P-TATTAACGTTTACAATTTAAATATTTGCTTATACAATCTTCCTGTTTTTG-3'(SEQ ID NO.142)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in FIG. 21, the Ago-PCR isothermal amplification of the present invention can be realized when the primer length is between 27nt and 50 nt.
EXAMPLE 11 various Ago can be subjected to Ago-PCR isothermal amplification
The specific system and reaction procedure for the isothermal amplification of Ago-PCR in this example 11 is shown in Table 13 below. Other procedures and conditions of the experimental procedure, etc., refer to example 7 of the present invention.
TABLE 13
The primers used in this example are as follows:
P-oM13-3：
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.143)
P-oM13-4：
5'P-TATTAACGTTTACAATTTAAATATTTGCTTATACAATCTTCCTGTTTTTG-3'(SEQ ID NO.144)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in FIG. 22, various Agos such as CalAgo, ssAgo, DIAgo, kpAgo, marAgo, poAgo, tcAgo, thAgo, bwAgo can be amplified at constant temperature.
Example 12Ago protein promotes M13mp18 double-stranded
In the absence of Ago, the complementary sequences of primer and template M13 are randomly collision-paired, and under the action of polymerase, the M13 single strand becomes double strand. In the presence of Ago, the primer rapidly binds to the complementary sequence of template M13 under the promotion of Ago, and the single strand of M13 becomes double-stranded under the action of polymerase. The comparison experiment result shows that the efficiency of targeting target by using the M13 double-stranded efficiency reaction primer is less than M13 double-stranded when no Ago participates; in the presence of Ago, almost all M13 was double-stranded. The specific results are shown in FIGS. 23-25. Table 14 below shows the specific system and reaction procedure for the Ago protein to promote M13mp18 duplex in this example.
TABLE 14
In this example the Ago protein was the dmCalago protein, the template was M13mp18 single stranded circularized DNA,
the primers used were as follows:
P-oM13-13-50
5'P-TTGTATAAGCAAATATTTAAATTGTAAACGTTAATATTTTGTTAAAATTC(SEQ ID NO.145)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in fig. 23, there was little M13 double-stranded without Ago participation; in the presence of Ago, almost all M13 was double-stranded.
Table 15 below shows the specific system and reaction procedure for qPCR instrument detection of Ago protein to promote M13mp18 duplex.
TABLE 15
As shown in FIG. 24, in the absence of Ago, the complementary sequences of the primer and the template M13 are randomly collisional paired, and under the action of polymerase, the M13 single strand becomes double strand.
In the presence of Ago, the primer rapidly binds to the complementary sequence of template M13 under the promotion of Ago, and the single strand of M13 becomes double-stranded under the action of polymerase.
SBRYGreen I binds double-stranded DNA and emits strong fluorescence, and the fluorescent signal is captured by a qPCR instrument, revealing the M13mp18 duplex process.
As shown in FIG. 25, the fluorescence signal rapidly increased in the presence of Ago protein, indicating that a large amount of M13mp18 single-stranded DNA was double-stranded in a short period of time; in the absence of Ago protein, the fluorescence signal changed slowly in a short time, indicating that only a small amount of M13mp18 single-stranded DNA was double-stranded.
Example 13 Ago protein promotes M13mp18 double-stranded can use different primer lengths
Table 16 below shows the specific system and reaction procedure for qPCR apparatus to detect different primer length Ago proteins to promote M13mp18 duplex.
Table 16
In the embodiment, the Ago protein is dmCalago protein, and the template is M13mp18 single-stranded circularized DNA;
the primers used in this example are as follows:
different primers:
P-oM13-3-27：5'P-TTAAATATGCAACTAAAGTACGGTGTC-3'(SEQ ID NO.146)
P-oM13-3-30：5'P-TTAAATATGCAACTAAAGTACGGTGTCTGG-3'(SEQ ID NO.147)
P-oM13-3-40：5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATT-3'(SEQ ID NO.148)
P-oM13-3-50：
5'P-TTAAATATGCAACTAAAGTACGGTGTCTGGAAGTTTCATTCCATATAACA-3'(SEQ ID NO.149)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in FIG. 26, when the primer length was 27-50nt, the fluorescence signal rose rapidly, indicating that a large amount of M13mp18 single-stranded DNA was double-stranded in a short time when the primer length was 27-50 nt.
Example 14Ago protein was able to efficiently promote M13mp18 double-stranded using both 5'P primer and 5' OH primer
Table 17 shows the specific system and reaction procedure for qPCR instrument detection of Ago protein using 5'P primer and 5' OH primer to promote M13mp18 duplex.
TABLE 17
In this example the Ago protein is the dmCalago protein and the template is M13mp18;
the primers used were as follows:
5'P primer (No. 1, no. 2):
P-oM13-13-50
5'P-TTGTATAAGCAAATATTTAAATTGTAAACGTTAATATTTTGTTAAAATTC-3'(SEQ ID NO.150)
5' OH primer (No. 3, no. 4):
oM13-13-50
5'OH-TTGTATAAGCAAATATTTAAATTGTAAACGTTAATATTTTGTTAAAATTC-3'(SEQ ID NO.151)
1 Xbuffer component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;4mM MgSO4;0.1%20；pH8.8
As shown in FIG. 27, the Ago protein promoted M13mp18 double-stranded, using both 5'P primer and 5' OH primer was efficient, and the phosphorylated primer was faster and more efficient.
Example 15 method for amplifying nucleic acid by Ago-RT-PCR
Argonaute (Ago) protein and primer are fast and specifically combined with a template RNA single chain, then under the action of reverse transcriptase, first strand cDNA is synthesized, and then Ago-PCR amplification is carried out by taking the first strand cDNA as a template.
Table 18 shows the specific reaction system and reaction procedure of Ago-RT (reverse transcription involving dmMbpago protein).
TABLE 18
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Table 19 shows the specific reaction system and reaction procedure for detecting the Ago-RT product by Ago-PCR.
TABLE 19
/>
Table 20 shows the specific reaction system and reaction procedure for template RNA preparation.
TABLE 20 Synthesis of double-stranded DNA templates with T7 promoter
Transcription of template RNA
DNase I digestion
/>
The primers in this example are:
primer 1:5'-CCGCTACAGGGCGCGTACTATGGTTGCTTT-3' (SEQ ID NO. 152)
Primer 2:
5'-TTGCAATGGCTGGCGGTAATATTGTTCTGGATATTACCAGCAAGGCCGAT-3'(SEQ ID NO.153)
primer 3:
5'-CCGCTACAGGGCGCGTACTATGGTTGCTTTGACGAGCACGTATAACGTGC-3'(SEQ ID NO.154)
primer 4:
5'-TATATAATACGACTCACTATAGGTGGCGATGTTTTAGGGCTATCAGTT-3'(SEQ ID NO.155)
primer 5:5'-GGCGCTGGCAAGTGTAGCGGTCA-3' (SEQ ID NO. 156)
Taq man probe F-M13-4Y:
5'FAM-TCAGAGCGGGAGCTAAACAGGAGGCCG-3'BHQ1(SEQ ID NO.157)
1X IsothermalAmplification Buffer Pack component 20mM Tris-HCl;10mM (NH 4) 2SO4;50mM KCl;2mM MgSO4;0.1%20；pH8.8
Preparation of template RNA
1.1 Synthesis of double-stranded DNA templates with T7 promoter
10uM of the upstream primer 4 (with T7 promoter) 1ul,10uM of the downstream primer 5 1ul,2x Taq PCR Master Mix (TIANGEN#KT201) 10ul,4fmol/ul of M13mp18 SSDNA (NEB#N4040S) 2ul, and ddH was added 2 O6 ul, 20ul overall. Slightly oscillating by using an oscillator, centrifuging for a plurality of seconds by using a palm type centrifugal machine, and placing the mixture into a PCR instrument for reaction, wherein the reaction procedure is as follows: step1, 95℃for 3min, step2, 95℃for 30s, step3, 65℃for 30s, step4, 72℃for 30s, step5, 72℃for 5min. step2-4 cycles 30 rounds.
1.2 transcription of template RNA
1.2.1 transcription of RNA
Diluting the recovered DNA template to 30ng/ul, taking 1ul,Ribonucleotide Solution Mix (NEB#M0466S) 4ul,T7 RNAPolymerase Mix (NEB#M0255A) 1ul,10x T7 Reation Buffer 2ul,DEPC H 2 O12ul, 20ul overall. The mixture was gently shaken by an oscillator, centrifuged in a palm centrifuge for several seconds, and placed in a PCR instrument for reaction. The reaction procedure was 37℃for 2 hours.
1.2.2 DNase I digestion
After transcription, 5ul DNase I (Thermo Scientific #EN 0521), 10ul DNase I Reaction Buffer (Thermo Scientific #B43) and DEPC H were added to the system 2 O65 ul. The mixture was gently shaken by an oscillator, centrifuged in a palm centrifuge for several seconds, and placed in a PCR instrument for reaction. The reaction procedure was 37℃for 1 hour.
1.2.3 RNA purification recovery
1ml TRNZOL (TIANGEN#U8825) and 1.5EP were taken, DNase I digested product was added thereto, mixed well, added with 200ul of chloroform, vigorously shaken for 15s, and allowed to stand at room temperature for 10min. After the standing is finished, the mixture is put into a small high-speed centrifuge, and the rotation speed is 12000rmp/min, and the mixture is centrifuged for 15min. Centrifuging, collecting supernatant, adding into new 1.5ml EP tube, adding equal volume of isopropanol, mixing, placing into a refrigerator at-20deg.C, and refrigerating for 30min. After the cold storage is finished, put in a small High-speed centrifugal machine, rotational speed 12000rmp/min, centrifugal 5min. The pellet was placed at the bottom of the EP tube, the supernatant was discarded, and the tube was washed three times with 75% ethanol. Finally 50ul of DEPC H is added 2 O is dissolved, and after uniform mixing, the concentration of RNA is quantified by a multifunctional micrometer.
Reverse transcription involving 2 dmMbpago protein (A System component)
2.1 Incubation of dmMbpago protein with primer 1 (reverse transcription primer)
Preparation of system 1: primer 1 was diluted to 100fmol/ul and 1ul,10x IsothermalAmplification Buffer Pack (NEB#B0573S) was taken to 1ul,50mM MgSO 4 0.8ul of BSA (NEB#B9000S) was taken, 0.1ul,40U/ul of RNase Inhibitor (Thermo Scientific Ribolock RNase Ihibitor #E00382) was taken, 0.3ul, and DEPC H was finally added 2 O6.8 ul, total system 10ul. Preparing a system 2: dmMbpago (1 ug/ul) 0.5ul, primer 1 (100 fmol/ul) 1ul,10x Isothermal Amplification Buffer Pack (NEB#B0573S) 1ul,50mM MgSO 4 0.8ul of BSA (NEB#B9000S) was taken, 0.1ul,40U/ul of RNase Inhibitor (Thermo Scientific RibolockRNase Ihibitor #E00382) was taken, 0.3ul, and DEPC H was finally added 2 O6.3ul, overall 10ul. The system 1 and the system 2 are placed in a shaker to slightly vibrate, and are centrifuged in a palm centrifuge for a plurality of seconds, and are placed in a PCR (BIO-RAD) instrument for incubation, wherein the incubation procedure is that the incubation time is 10min at 37 ℃.
2.2 reverse transcription reaction System
Diluting transcribed RNA template with length of 600nt and GC content of 45% to concentration of 10 -1 fmol/ul, 2ul, dNTP (Producer #B500056-0500) and 1ul,10x IsothermalAmplification Buffer ul,50mM MgSO 4 1.6ul,Bst3.0 DNApolymerase (NEB#M0374L) 1ul,40U/ul RNase Inhibitor 0.4ul and DEPC water 12ul. After slight shaking by an oscillator, the mixture was centrifuged again in a palm centrifuge for several seconds, and 10ul of the mixture was dispensed into the PCR tube of system 1, and the remaining 10ul of the mixture was dispensed into the PCR tube of system 2, with the total system being 20ul. Then, the mixed system 1 and system 2 are put into an oscillator to slightly vibrate, and are centrifuged for a plurality of seconds by a palm centrifuge, and are put into a PCR (BIO-RAD) instrument to carry out RT reaction, wherein the reaction procedure is 60 DEG CThe reaction time was 30min.
3 Ago-PCR detection of Ago-RT products
3.1 MlAgo protein incubation primer (B System component)
Taking 3ug/ul of 40Ml-Ago 1.4ul, diluting the primer2, primer3 to 1.5pmol/ul, and taking 2ul,10x IsothermalAmplification Buffer ul of each, 50mM MgSO 4 0.8ul of BSA was taken, 20mg/ml BSA was taken at 0.2ul, and finally ddH was used 2 O made up the system to 20ul. Slightly vibrating with an oscillator, centrifuging in a palm centrifuge for several seconds, taking 10ul of the mixture, and subpackaging the mixture into another PCR tube to obtain a 40Ml-Ago detection system 1, and taking the remaining 10ul of the mixture as a 40Ml-Ago detection system 2. Systems 1 and 2 were incubated in a PCR (BIO-RAD) apparatus at 55deg.C for 15min.
3.2 Ago-PCR detection with MlAgo participation (C System component)
To detection System 1 in the B System fraction at the end of incubation, 0.5ul dNTP,1ul Taq DNApolymerase of 10x Isothermal Amplification BufferPack,0.5ul (NEB#30273L), 0.5ul Taq Man probe F-M13-4Y (10 uM), 0.4ul 50mM MgSO were added 4 4.6ul of ddH 2 O and 2.5ul of group A system 1, 20ul overall. To detection System 2 in the B System fraction at the end of incubation, 0.5ul of dNTP,1ul of Taq DNApolymerase (NEB#B0320L) of 10x IsothermalAmplification BufferPack,0.5ul, 0.5ul of Taq man probe F-M13-4Y (10 uM), 0.4ul of 50mM MgSO were added 4 4.6ul of ddH 2 O and 2.5ul of group A system 2, 20ul of total system. And then slightly oscillating by using an oscillator, centrifuging for a plurality of seconds by using a palm type centrifugal machine, transferring the mixed solution of the reaction systems 1 and 2 into eight rows of PCR tubes matched with a real time PCR instrument respectively, and adding 10ul of mineral oil. After the matched cover is covered, the mixture is centrifuged for a few seconds by a palm type centrifuge, and a real time PCR instrument (BIO-RAD) is placed for reaction, wherein the reaction procedure is 85 ℃,1min,68 ℃,30s, photographing and 50C.
As shown in fig. 29, in the RNA reverse transcription experiments without participation of dmMbpAgo protein, there was no fluorescent signal; in RNA reverse transcription experiments with dmMbpago protein, there was a fluorescent signal.
As shown in FIG. 30, no band of interest was detected in the RNA reverse transcription experiments without participation of dmMbpago protein; in RNA reverse transcription experiments with dmMbpago protein, the band of interest was targeted.
The present invention has advantages including, but not limited to: high detection limit and amplification efficiency of PCR. The sensitivity is high, and trace target nucleic acid can be detected in the mixed template. The flexibility is strong, and can not only identify the DNA template, but also identify the RNA template. Can be reacted at a higher temperature or at normal temperature. The method is suitable for both temperature-variable amplification and constant-temperature amplification. The amplification can be performed at different temperatures without being limited by the annealing temperature of the primer. The primer consumption is reduced, and the detection time is shortened.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that would occur to one skilled in the art are included in the invention without departing from the spirit and scope of the inventive concept, and the scope of the invention is defined by the appended claims.
SEQUENCE LISTING
<110> Hangzhou micro-computer technology Co., ltd
<120> an Ago protein/PIWI domain-containing protein-based nucleic acid polymerization method and application
<160> 157
<170> PatentIn version 3.3
<210> 1
<211> 886
<212> PRT
<213> artificial sequence
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Thr Val Ile Asp Leu Asp Ser Thr Thr Thr Ala Asp Glu Leu Thr Ser
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Gly His Thr Tyr Asp Ile Ser Val Thr Leu Thr Gly Val Tyr Asp Asn
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Thr Asp Glu Gln His Pro Arg Met Ser Leu Ala Phe Glu Gln Asp Asn
35 40 45
Gly Glu Arg Arg Tyr Ile Thr Leu Trp Lys Asn Thr Thr Pro Lys Asp
50 55 60
Val Phe Thr Tyr Asp Tyr Ala Thr Gly Ser Thr Tyr Ile Phe Thr Asn
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Ile Asp Tyr Glu Val Lys Asp Gly Tyr Glu Asn Leu Thr Ala Thr Tyr
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Gln Thr Thr Val Glu Asn Ala Thr Ala Gln Glu Val Gly Thr Thr Asp
100 105 110
Glu Asp Glu Thr Phe Ala Gly Gly Glu Pro Leu Asp His His Leu Asp
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Asp Ala Leu Asn Glu Thr Pro Asp Asp Ala Glu Thr Glu Ser Asp Ser
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Gly His Val Met Thr Ser Phe Ala Ser Arg Asp Gln Leu Pro Glu Trp
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Thr Leu His Thr Tyr Thr Leu Thr Ala Thr Asp Gly Ala Lys Thr Asp
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Thr Glu Tyr Ala Arg Arg Thr Leu Ala Tyr Thr Val Arg Gln Glu Leu
180 185 190
Tyr Thr Asp His Asp Ala Ala Pro Val Ala Thr Asp Gly Leu Met Leu
195 200 205
Leu Thr Pro Glu Pro Leu Gly Glu Thr Pro Leu Asp Leu Asp Cys Gly
210 215 220
Val Arg Val Glu Ala Asp Glu Thr Arg Thr Leu Asp Tyr Thr Thr Ala
225 230 235 240
Lys Asp Arg Leu Leu Ala Arg Glu Leu Val Glu Glu Gly Leu Lys Arg
245 250 255
Ser Leu Trp Asp Asp Tyr Leu Val Arg Gly Ile Asp Glu Val Leu Ser
260 265 270
Lys Glu Pro Val Leu Thr Cys Asp Glu Phe Asp Leu His Glu Arg Tyr
275 280 285
Asp Leu Ser Val Glu Val Gly His Ser Gly Arg Ala Tyr Leu His Ile
290 295 300
Asn Phe Arg His Arg Phe Val Pro Lys Leu Thr Leu Ala Asp Ile Asp
305 310 315 320
Asp Asp Asn Ile Tyr Pro Gly Leu Arg Val Lys Thr Thr Tyr Arg Pro
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Arg Arg Gly His Ile Val Trp Gly Leu Arg Asp Glu Cys Ala Thr Asp
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Ser Leu Asn Thr Leu Gly Asn Gln Ser Val Val Ala Tyr His Arg Asn
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Asn Gln Thr Pro Ile Asn Thr Asp Leu Leu Asp Ala Ile Glu Ala Ala
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Val Ser Phe Pro Gln Glu Leu Leu Ala Val Glu Pro Asn Thr His Gln
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Ile Lys Gln Phe Ala Ser Asp Gly Phe His Gln Gln Ala Arg Ser Lys
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Thr Arg Leu Ser Ala Ser Arg Cys Ser Glu Lys Ala Gln Ala Phe Ala
435 440 445
Glu Arg Leu Asp Pro Val Arg Leu Asn Gly Ser Thr Val Glu Phe Ser
450 455 460
Ser Glu Phe Phe Thr Gly Asn Asn Glu Gln Gln Leu Arg Leu Leu Tyr
465 470 475 480
Glu Asn Gly Glu Ser Val Leu Thr Phe Arg Asp Gly Ala Arg Gly Ala
485 490 495
His Pro Asp Glu Thr Phe Ser Lys Gly Ile Val Asn Pro Pro Glu Ser
500 505 510
Phe Glu Val Ala Val Val Leu Pro Glu Gln Gln Ala Asp Thr Cys Lys
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Ala Gln Trp Asp Thr Met Ala Asp Leu Leu Asn Gln Ala Gly Ala Pro
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Pro Thr Arg Ser Glu Thr Val Gln Tyr Asp Ala Phe Ser Ser Pro Glu
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Ser Ile Ser Leu Asn Val Ala Gly Ala Ile Asp Pro Ser Glu Val Asp
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Ala Ala Phe Val Val Leu Pro Pro Asp Gln Glu Gly Phe Ala Asp Leu
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Ala Ser Pro Thr Glu Thr Tyr Asp Glu Leu Lys Lys Ala Leu Ala Asn
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Met Gly Ile Tyr Ser Gln Met Ala Tyr Phe Asp Arg Phe Arg Asp Ala
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Lys Ile Phe Tyr Thr Arg Asn Val Ala Leu Gly Leu Leu Ala Ala Ala
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Gly Gly Val Ala Phe Thr Thr Glu His Ala Met Pro Gly Asp Ala Asp
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Tyr Gln Gln Val Thr Gly Glu Ser Pro Thr His Ile Val Ile His Arg
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Ser Ile Ala Ala Ile Asn Gln Asn Glu Pro Arg Ala Thr Val Ala Thr
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Leu Thr Arg Gln Val Tyr Leu Leu Ser Gln Ser His Ile Gln Val His
835 840 845
Asn Ser Thr Ala Arg Leu Pro Ile Thr Thr Ala Tyr Ala Asp Gln Ala
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Ser Thr His Ala Thr Lys Gly Tyr Leu Val Gln Thr Gly Ala Phe Glu
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Asn Tyr Thr Ala Ala Asn Thr Ala Asn Ser Pro Ile Phe Leu Ser Glu
1 5 10 15
Ile Ser Ser Leu Thr Leu Lys Asn Ser Cys Leu Asn Cys Phe Gln Leu
20 25 30
Asn His Gln Val Thr Arg Lys Ile Gly Asn Arg Phe Ser Trp Gln Phe
35 40 45
Ser Arg Lys Phe Pro Asp Val Val Val Ile Phe Glu Asp Asn Cys Phe
50 55 60
Trp Val Leu Ala Lys Asp Glu Lys Ser Ile Pro Ser Leu Gln Gln Trp
65 70 75 80
Lys Glu Ala Leu Ser Asp Ile Gln Glu Val Leu Arg Glu Asp Ile Gly
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Asp His Tyr Tyr Ser Ile His Trp Leu Lys Asp Phe Gln Ile Thr Ala
100 105 110
Leu Val Thr Ala Gln Leu Ala Val Arg Ile Leu Lys Ile Phe Gly Lys
115 120 125
Phe Ser Asp Pro Ile Val Phe Pro Lys Asp Ser Gln Ile Ser Glu Asn
130 135 140
Gln Val Gln Val Arg Arg Glu Val Asn Phe Trp Ala Glu Ile Ile Asn
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Asp Thr Asp Pro Ala Ile Cys Leu Thr Val Asp Ser Ser Ile Val Tyr
165 170 175
Ser Gly Asp Leu Glu Gln Phe Tyr Glu Asn His Pro Tyr Arg Gln Asp
180 185 190
Ala Val Lys Leu Leu Val Gly Leu Lys Val Lys Asp Arg Glu Thr Asn
195 200 205
Gly Thr Ala Lys Ile Ile Arg Ile Ala Gly Arg Ile Gly Glu Arg Arg
210 215 220
Glu Asp Leu Leu Thr Lys Ala Thr Gly Ser Ile Ser Arg Arg Lys Leu
225 230 235 240
Glu Glu Ala His Leu Gly Gln Pro Val Val Ala Val Gln Phe Gly Lys
245 250 255
Asn Pro Gln Glu Tyr Ile Tyr Pro Leu Ala Ala Leu Lys Pro Trp Val
260 265 270
Thr Asp Glu Asp Glu Ser Leu Phe Gln Val Asn Tyr Gly Asn Leu Leu
275 280 285
Lys Ala Thr Lys Ile Phe Tyr Ala Glu Arg Gln Glu Leu Leu Lys Leu
290 295 300
Tyr Lys Gln Glu Ala Gln Lys Ala Leu Asn Asn Phe Gly Phe Gln Leu
305 310 315 320
Arg Glu Lys Ser Ile Asn Ser Gln Glu Tyr Pro Glu Leu Phe Trp Thr
325 330 335
Pro Ser Ile Ser Ile Glu Gln Thr Pro Ile Leu Phe Gly Gln Gly Glu
340 345 350
Arg Gly Glu Lys Arg Glu Ile Ile Lys Gly Leu Ser Lys Gly Gly Val
355 360 365
Tyr Lys Arg His Arg Glu Tyr Val Asp Pro Ala Arg Lys Ile Arg Leu
370 375 380
Ala Ile Leu Lys Pro Ala Asn Leu Lys Val Gly Asp Phe Arg Glu Gln
385 390 395 400
Leu Glu Lys Arg Leu Lys Leu Tyr Lys Phe Glu Thr Ile Leu Pro Pro
405 410 415
Glu Asn Gln Ile Asn Phe Ser Val Glu Gly Leu Gly Phe Glu Lys Arg
420 425 430
Ala Arg Leu Glu Glu Ala Val Asp Arg Leu Ile Gly Val Glu Ile Pro
435 440 445
Val Asp Ile Ala Leu Val Phe Leu Pro Gln Glu Asp Arg Asn Ala Asp
450 455 460
Asn Thr Glu Glu Gly Ser Leu Tyr Ser Trp Ile Lys Arg Lys Phe Leu
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Gly Arg Gly Val Ile Thr Gln Met Ile Tyr Glu Lys Thr Leu Asn Asp
485 490 495
Lys Ser Asn Tyr Lys Asn Ile Leu Asn Gln Val Val Pro Gly Ile Leu
500 505 510
Ala Lys Leu Gly Asn Leu Pro Tyr Val Leu Ala Glu Pro Leu Glu Ile
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Ala Asp Tyr Phe Ile Gly Leu Asp Val Gly Arg Met Pro Lys Lys Asn
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Leu Pro Gly Ser Leu Asn Val Cys Ala Ser Val Arg Leu Tyr Gly Lys
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Gln Gly Glu Phe Val Arg Cys Arg Val Glu Asp Ser Leu Thr Glu Gly
565 570 575
Glu Glu Ile Pro Gln Arg Ile Leu Glu Asn Cys Leu Pro Gln Ala Glu
580 585 590
Leu Lys Asn Gln Thr Val Leu Ile Tyr Arg Asp Gly Lys Phe Gln Gly
595 600 605
Lys Glu Val Glu Asn Leu Leu Ala Arg Ala Arg Ala Ile Asn Ala Lys
610 615 620
Phe Ile Leu Val Glu Cys Tyr Lys Thr Gly Ile Pro Arg Leu Tyr Asn
625 630 635 640
Leu Gln Gln Lys Gln Ile Asn Ala Pro Ser Lys Gly Leu Ala Leu Ala
645 650 655
Leu Ser Asn Arg Glu Val Ile Leu Ile Thr Ser Gln Val Ser Glu Gln
660 665 670
Ile Gly Val Pro Arg Pro Leu Arg Leu Lys Val His Glu Leu Gly Glu
675 680 685
Gln Arg Asn Leu Lys Gln Leu Val Asp Thr Thr Leu Lys Leu Thr Leu
690 695 700
Leu His Tyr Gly Ser Leu Lys Asp Pro Arg Leu Pro Ile Pro Leu Tyr
705 710 715 720
Gly Ala Asp Ile Ile Ala Tyr Arg Arg Leu Gln Gly Ile Tyr Pro Ser
725 730 735
Leu Leu Glu Asp Asp Cys Gln Phe Trp
740 745
<210> 3
<211> 863
<212> PRT
<213> artificial sequence
<400> 3
Met Val Lys Arg Tyr Ile Ser Phe His Leu Phe Pro Arg Ile Lys Leu
1 5 10 15
Cys Gly Val Tyr Leu Cys Leu Arg Met Asn Thr Lys Asp Asp Ile Ala
20 25 30
His Lys Gln Pro Ile Thr Ile Glu Val Gln Val Leu Lys Glu Leu Asp
35 40 45
Lys Pro Ser Pro Lys Met Ala Thr Arg Leu Leu Val Ala Asp Arg Ala
50 55 60
Gly Asn Arg Phe Pro Leu Ala Ile Trp Lys Asn Asn Ala Leu Ser Asp
65 70 75 80
Tyr Asp Trp Thr Ile Gly Gln Trp Tyr Arg Leu Glu Asn Ala Arg Gly
85 90 95
Asn Val Phe Asn Gly Lys Gln Ser Leu Asn Gly Ser Ser Asn Met Arg
100 105 110
Ala Thr Pro Leu Glu Ala Ser Glu Glu Asp Glu Thr Arg Ala Asp Asp
115 120 125
Val Gly Arg Val Asp Thr Ile Leu Gly Asn Leu Ser Pro Asn Gln Ala
130 135 140
Tyr Leu Ser Leu Phe Pro Ile Ser Arg Ser Phe Asp Thr Leu Ser Val
145 150 155 160
Tyr Glu Tyr Ser Ile Glu Ala Ala Glu Ala Phe Glu Asp Asp Pro Asp
165 170 175
Thr Val Thr Tyr Gln Cys Ala Gly Arg Leu Arg Arg Ile Thr Gly Ala
180 185 190
Gly Val Ala Tyr Ala Gly Pro Met Gln Ile Val Ser Thr Arg Lys Leu
195 200 205
Pro Asp Lys Leu Ala Asp Pro Phe Ser Leu Ser Glu Pro Thr Glu Arg
210 215 220
Glu Leu Lys Ala Ala Asp Ala Arg Asp Arg His Arg Ile Glu Arg Leu
225 230 235 240
Leu Lys Ser Leu Val Lys Ala Ala Ile Asp Asp Ser Thr Tyr Asp Pro
245 250 255
Tyr Gln Ile Asn Arg Ile Arg Ala Arg Thr Pro Ala Ile Thr Ala Gly
260 265 270
Asp Gly Leu Phe Glu Ala Cys Tyr Glu Phe Ala Ala Arg Val Asp Val
275 280 285
Met Pro Ser Gly Asp Ala Phe Val Gly Ile Glu Val Arg Tyr His Ala
290 295 300
Arg Ser Gln Val Thr Ala Asp Val Tyr Glu Asp Lys Thr Gly Glu Leu
305 310 315 320
Val Gly Thr Ile Val Glu His Asp Pro Glu Arg Tyr Asn Val Ser Gly
325 330 335
Thr Gly Arg Val Val Gly Phe Thr Asp His Tyr Phe Thr Asp Ala Leu
340 345 350
Asp Glu Leu Gly Gly Leu Ser Leu Ala Asp Trp Tyr Ala Gln Lys Asp
355 360 365
Arg Val Pro Glu Gly Val Leu Glu Ala Leu Arg Glu Lys Asn Pro Arg
370 375 380
Leu Val Asp Ile Gln Tyr Gln Glu Asp Glu Pro Ala Gln Ile His Val
385 390 395 400
Pro Glu Leu Leu Arg Val Ala Pro Arg Lys Glu Val Val Lys Glu Leu
405 410 415
Asp Pro Thr Phe His Arg Arg Trp Asp Arg Glu Ala Lys Met Leu Pro
420 425 430
Asp Lys Arg Phe Arg His Ala Ile Glu Phe Val Asp His Leu Gly Ser
435 440 445
Leu Pro Asp Ile Asp Ala Thr Val Ala Pro Glu Pro Leu Gly Pro Ser
450 455 460
Leu Ser Tyr Met Ser Thr Ala Val Asp Arg Glu Glu Asn Leu Arg Phe
465 470 475 480
Lys Asp Gly Arg Thr Ala Thr Thr Pro Ser Ser Gly Ile Arg Ser Gly
485 490 495
Val Tyr Gln Gln Pro Thr Ser Phe Asp Ile Ala Tyr Val Tyr Pro Thr
500 505 510
Glu Ser Glu Gln Glu Ser Lys Gln Phe Ile Ser Asn Phe Glu Asn Lys
515 520 525
Leu Ser Arg Cys His Cys Glu Pro Thr Ala Thr Arg His Val Pro Tyr
530 535 540
Glu Leu Gly Gly Glu Leu Ser Tyr Leu Ala Val Ile Asn Glu Leu Glu
545 550 555 560
Ser Val Asp Ala Val Leu Ala Val Val Pro Pro Arg Asn Asp Asp Arg
565 570 575
Ile Ala Ala Gly Asp Ile Thr Asp Pro Tyr Pro Glu Phe Lys Lys Gly
580 585 590
Leu Gly Lys Gln Lys Val Pro Ser Gln Met Val Val Thr Glu Asn Leu
595 600 605
Asp Thr Arg Trp Val Met Asn Asn Thr Ala Met Gly Leu Ile Ala Gly
610 615 620
Ala Gly Gly Val Pro Trp Arg Val Asp Glu Met Pro Gly Glu Ala Asp
625 630 635 640
Cys Phe Ile Gly Leu Asp Val Thr Arg Asp Pro Glu Thr Gly Gln His
645 650 655
Leu Gly Ala Ser Ala Asn Val Val Tyr Ala Asp Gly Thr Val Phe Ala
660 665 670
Ser Lys Thr Gln Thr Leu Gln Ser Gly Glu Thr Phe Asp Glu Gln Ser
675 680 685
Ile Ile Asp Val Ile Lys Asp Val Phe Gln Glu Phe Val Arg Arg Glu
690 695 700
Gly Arg Ser Pro Glu His Ile Val Ile His Arg Asp Gly Arg Leu Phe
705 710 715 720
Glu Asp Ala Asp Glu Ile Gln Ala Pro Phe Ala Asp Ser Gly Val Ser
725 730 735
Ile Asp Ile Leu Asp Ile Arg Lys Ser Gly Ala Pro Arg Ile Ala Arg
740 745 750
Tyr Glu Asp Asn Ser Phe Lys Ile Asp Glu Lys Gly Arg Leu Phe Ile
755 760 765
Ser Gln Asp Asp Thr His Gly Phe Ile Ala Thr Thr Gly Lys Pro Glu
770 775 780
Phe Asp Asp Ser Asp Asn Leu Gly Thr Pro Lys Thr Leu Arg Val Val
785 790 795 800
Arg Arg Ala Gly Asp Thr Pro Met Leu Thr Leu Leu Lys Gln Val Tyr
805 810 815
Trp Leu Ser Glu Ala His Ile Gly Ser Val Ser Arg Ser Val Arg Leu
820 825 830
Pro Ile Thr Thr Tyr Tyr Ala Asp Arg Cys Ala Glu His Ala Arg Glu
835 840 845
Gly Tyr Leu Leu His Gly Glu Leu Ile Glu Gly Val Pro Tyr Leu
850 855 860
<210> 4
<211> 839
<212> PRT
<213> artificial sequence
<400> 4
Met Lys Thr Gln Asp Asp Ile Ala His Lys Gln Pro Ile Thr Ile Glu
1 5 10 15
Val Gln Ile Leu Lys Glu Leu Asp Lys Pro Ser Pro Lys Met Ala Thr
20 25 30
Arg Phe Leu Val Ala Asp Arg Asp Gly Asn Arg Phe Ser Leu Ala Ile
35 40 45
Trp Lys Asn Asn Ala Leu Ser Asp Tyr Asp Trp Thr Ile Gly Gln Trp
50 55 60
Tyr Arg Leu Glu Asn Ala Arg Gly Asn Val Phe Asn Gly Lys Gln Ser
65 70 75 80
Leu Asn Gly Ser Ser Lys Met Arg Ala Thr Pro Leu Glu Ala Ser Glu
85 90 95
Glu Asp Glu Thr Ser Thr Asp Asp Val Gly Arg Val Asp Thr Ile Leu
100 105 110
Gly Asn Met Ser Pro Asp Gln Ala Tyr Leu Ser Leu Phe Pro Ile Ser
115 120 125
Arg Ser Phe Asp Thr Leu Ser Val Tyr Glu Tyr Ser Ile Glu Ala Ala
130 135 140
Glu Ala Phe Glu Asp Ala Pro Asp Thr Val Thr Tyr Arg Cys Ala Gly
145 150 155 160
Arg Leu Arg Arg Ile Thr Gly Ala Gly Val Ala Tyr Ala Gly Ser Met
165 170 175
Arg Ile Val Ser Thr Arg Lys Leu Pro Asp Lys Leu Ala Asp Pro Phe
180 185 190
Ser Leu Ser Glu Pro Thr Glu Arg Glu Leu Asn Ala Thr Asp Ala Arg
195 200 205
Asp Arg His Arg Ile Glu Arg Leu Leu Lys Ser Leu Val Lys Ala Ala
210 215 220
Ile Asp Asp Ser Thr Tyr Asp Pro Tyr Gln Ile Asn Arg Ile Arg Ala
225 230 235 240
Arg Thr Pro Ser Ile Thr Ala Gly Asp Gly Leu Phe Glu Ala Cys Tyr
245 250 255
Glu Phe Ala Ala Arg Val Asp Val Met Pro Ser Gly Asp Ala Phe Val
260 265 270
Gly Ile Glu Val Arg Tyr His Thr Arg Ser Gln Val Thr Ala Asp Val
275 280 285
Tyr Glu Asp Lys Thr Ala Glu Leu Val Gly Thr Ile Val Glu His Asp
290 295 300
Pro Glu Arg Tyr Asn Ile Ser Gly Thr Gly Arg Val Val Gly Phe Thr
305 310 315 320
Asp His His Phe Thr Asp Ala Leu Asp Glu Leu Gly Gly Leu Ser Leu
325 330 335
Ala Asp Trp Tyr Ala Gln Lys Asp Arg Val Pro Glu Gly Val Leu Glu
340 345 350
Ala Leu Arg Glu Lys Asn Pro Arg Leu Val Asp Ile Gln Tyr Gln Glu
355 360 365
Asp Glu Pro Ala Arg Ile His Val Pro Asp Leu Leu Arg Val Ala Pro
370 375 380
Arg Lys Glu Val Val Lys Glu Leu Asp Pro Ala Phe His Arg Arg Trp
385 390 395 400
Asp Arg Glu Ala Lys Met Leu Pro Asp Lys Arg Phe Arg His Ala Ile
405 410 415
Glu Phe Val Asp His Leu Gly Ser Leu Pro Asp Ile Asp Ala Thr Val
420 425 430
Ala Pro Glu Pro Leu Gly Pro Ser Leu Ser Tyr Met Ser Thr Ala Val
435 440 445
Asp Arg Glu Lys Asn Leu Arg Phe Lys Asp Gly Arg Thr Ala Thr Thr
450 455 460
Pro Ser Ser Gly Ile Arg Ser Gly Val Tyr Gln Gln Pro Thr Ser Phe
465 470 475 480
Asp Ile Ala Tyr Val Tyr Pro Thr Glu Ser Glu Gln Glu Ser Lys Gln
485 490 495
Phe Ile Ser Asn Phe Glu Asn Lys Leu Ser Gln Cys Gln Cys Glu Pro
500 505 510
Thr Ala Ala Arg His Val Pro Tyr Glu Leu Gly Gly Glu Leu Ser Tyr
515 520 525
Leu Ala Val Ile Asn Glu Leu Glu Ser Val Asp Ala Val Leu Ala Val
530 535 540
Val Pro Pro Arg Asp Asp Asp Arg Ile Thr Ala Gly Asp Ile Thr Asp
545 550 555 560
Pro Tyr Pro Glu Phe Lys Lys Gly Leu Gly Lys Gln Lys Ile Pro Ser
565 570 575
Gln Met Ile Val Thr Glu Asn Leu Gly Thr Arg Trp Val Met Asn Asn
580 585 590
Thr Ala Met Gly Leu Ile Ala Gly Ala Gly Gly Val Pro Trp Arg Val
595 600 605
Asp Glu Met Pro Gly Glu Ala Asp Cys Phe Ile Gly Leu Asp Val Thr
610 615 620
Arg Asp Pro Glu Thr Gly Gln His Leu Gly Ala Ser Ala Asn Val Val
625 630 635 640
Tyr Ala Asp Gly Thr Val Phe Ala Ser Lys Thr Gln Thr Leu Gln Ser
645 650 655
Gly Glu Thr Phe Asp Glu Gln Ser Ile Ile Asp Val Ile Lys Asp Val
660 665 670
Phe Gln Glu Phe Val Arg Arg Glu Gly Arg Ser Pro Glu His Ile Val
675 680 685
Ile His Arg Asp Gly Arg Leu Phe Glu Asp Ala Asp Glu Ile Gln Ala
690 695 700
Pro Phe Ala Asp Ser Gly Val Ser Ile Asp Ile Leu Asp Ile Arg Lys
705 710 715 720
Ser Gly Ala Pro Arg Ile Ala Gln Tyr Glu Asp Asn Ser Phe Lys Ile
725 730 735
Asp Glu Lys Gly Arg Leu Phe Ile Ser Gln Asp Asp Thr His Gly Phe
740 745 750
Ile Ala Thr Thr Gly Lys Pro Glu Phe Asp Asp Ser Asp Asn Leu Gly
755 760 765
Thr Pro Lys Thr Leu Arg Val Val Arg Arg Ala Gly Asp Thr Pro Met
770 775 780
Leu Thr Leu Leu Lys Gln Val Tyr Trp Leu Ser Glu Ala His Val Gly
785 790 795 800
Ser Val Ser Arg Ser Val Arg Leu Pro Ile Thr Thr Tyr Tyr Ala Asp
805 810 815
Arg Cys Ala Glu His Ala Arg Glu Gly Tyr Leu Leu His Gly Glu Leu
820 825 830
Ile Glu Gly Val Pro Tyr Leu
835
<210> 5
<211> 887
<212> PRT
<213> artificial sequence
<400> 5
Val Lys Thr Asp Ile Glu Asp Gly Lys Gln Ile Asp Ile Ser Leu Arg
1 5 10 15
Val Thr Gly Thr Asp Glu Trp Asp His Asp Ala Ile Ala Arg Lys Val
20 25 30
Gln Leu Glu Asp Val Glu Gly Thr Pro Val Glu Leu Thr Val Phe His
35 40 45
Asn Asn Glu Ile Ala Asp Phe Glu Trp Asp Asp Glu Arg Trp Tyr Val
50 55 60
Leu Glu Asn Val Val Gly Asn Glu Tyr Arg Gly Glu Met Gln Leu Asn
65 70 75 80
Pro Gly Tyr Asp Leu Ile Val Thr Pro Leu Asp Glu Pro Pro Ala Ala
85 90 95
Ala Glu Asn Gly Gly Ala Glu Asn Thr Ser Ala Thr Gln Ser Ser Glu
100 105 110
Ser Gly Asp Ser Gly Ser Ser Thr Glu Ala Asp Gln Ser Ala Glu Ser
115 120 125
Glu Ser Ala Arg Glu Ser Glu Val Thr Ser Glu Pro Arg Pro Thr Ala
130 135 140
Asp Gly Gly Gly Glu Leu Leu His Gln Gln Pro Leu Ser Glu Gly Asn
145 150 155 160
Tyr Leu Leu Gln Phe Glu Leu Gly Asp Leu Pro Glu Leu Thr Val His
165 170 175
Glu Tyr Glu Leu Arg Ala Thr Gly Ser Gly Gly Ile Asn Pro Asp Asp
180 185 190
Phe Thr Asn Gly Ile Glu Gly Phe Thr Ala Lys Ala Ala Asn Tyr Tyr
195 200 205
Gln Ser Arg Ile Asn Ser Pro Val Thr Thr Ala Asp Ala Ser Arg Arg
210 215 220
Arg Ile Tyr Ala Thr Glu Lys Leu His Gly Lys Ile Ser Ile His Gly
225 230 235 240
Tyr Thr Val Lys Pro Val His Gln Gly Glu Thr Thr Leu Glu Ala Arg
245 250 255
Ser Tyr Thr Asp Asp Gly Pro Leu Gln Glu Phe Val Lys Gln Asp Val
260 265 270
Lys Arg Ala Val Ala Gly Arg Phe Glu Val Ser Gly Ile Asp Ser Ile
275 280 285
Ile Glu Pro Thr Pro Gln Arg Thr Ala Asn Ser Gly Leu Phe Glu Ala
290 295 300
Tyr Arg Lys Tyr Lys Cys Arg Ile Arg Val Asp Ala Asp Gly Thr Val
305 310 315 320
Ile Cys Gly Val Asn Val Ala Tyr His Leu Glu Ser Thr Phe Ser Ala
325 330 335
Ala Asp Trp Val Gln Arg Gly His Asp Ile Ala Glu Val Thr Val Glu
340 345 350
His Asp Thr Asp Leu Tyr Asp Ser Ala Arg Thr Ala Thr Val Lys Glu
355 360 365
Val Ile Asp Met Asp Tyr Asp Asp Val Leu Asp Gly Pro Gly Val Pro
370 375 380
Met Ser Glu Tyr His Glu Gln His Val Glu Gln Asp Val Ile Asn Ser
385 390 395 400
Met Gln Ala Gly Asp Pro Ile Ile Ala Asp Leu Gln Tyr Gly Ser Asp
405 410 415
Glu Asp Ser Ile Phe Pro Gln Leu Leu Glu Tyr Cys Lys Val Ile Pro
420 425 430
Thr Phe Asp Gln Leu Gly Ser Val Asp Asp Thr Phe Leu Asp Val Ile
435 440 445
His Asn Glu Ser Arg Met Glu Pro Glu Glu Arg Phe Ser Val Val Thr
450 455 460
Ser Phe Val Asp Leu Leu Gly Pro Thr Pro Tyr Phe Ser Phe Asp Pro
465 470 475 480
Val Pro Gln Pro Thr Asn Ala Gly Tyr Arg Glu His Lys Thr Pro Asn
485 490 495
Thr Pro Asn Leu Arg Phe Gly Asp Gly Lys Thr Gly Phe Tyr Gly Ala
500 505 510
Gly Gly Leu Glu Arg Lys Gly Tyr Gly Ile Tyr Lys Ala Pro Glu Ser
515 520 525
Phe Asp Ile Ile Ala Leu Tyr Pro Glu Asp Glu Glu Asp Asp Ala Arg
530 535 540
Pro Tyr Val Leu Ser Leu Leu Asn Lys Leu Ala Asp Tyr Asp Ala Gly
545 550 555 560
Pro Thr Val Phe Asp Gln Glu Thr Tyr Glu Leu Gly Ser Glu Phe His
565 570 575
Tyr Ser Gln His Ala Gln Lys Ala Ser Asp Tyr Asp Ala Ala Leu Ile
580 585 590
Val Val Pro Asp Ala Asp Lys Ala Ala Ala Ala Asp Tyr Asp Asp Pro
595 600 605
Tyr Pro Glu Phe Lys Arg Arg Leu Gly Gln Leu Gly Val Pro Ser Gln
610 615 620
Met Ile Ser Val Asp Asn Leu Gly Asn Asp Asn Tyr Arg Gly Asn Ile
625 630 635 640
Cys Ser Ser Leu Ile Gly Lys Ala Gly Gly Val Pro Trp Arg Ile Asp
645 650 655
Asp Val Pro Gly Asp Val Asp Ala Phe Val Gly Leu Asp Val Thr Tyr
660 665 670
Asp His Ala Thr Lys Gln His Leu Gly Ala Ala Ala Asn Val Ile Met
675 680 685
Ala Asp Gly Thr Ile Leu Ala Ser Glu Ala Val Thr Lys Gln Ala Gly
690 695 700
Glu Thr Phe Asp Glu Asp Asp Val Ala Asn Val Ile Lys His Val Leu
705 710 715 720
Glu Ile Phe Ala Glu Glu Glu Gly Arg Pro Pro Arg His Val Val Ile
725 730 735
His Arg Asp Gly Lys Phe Tyr Leu Asp Val Glu Asn Leu Val Lys Arg
740 745 750
Leu Asp Lys Ala Arg Asp Leu Ile Gln Arg Phe Asp Leu Val Glu Ile
755 760 765
Arg Lys Ser Gly Asn Pro Arg Ile Ala Ala Tyr Asp Glu Ser Glu Ser
770 775 780
Arg Phe Asp Ile Ala Asp Lys Gly Ile Ala Phe His Val His Asn Gly
785 790 795 800
Asp His Ser Tyr Leu Thr Thr Thr Gly Gly Arg Glu Gly Ser Pro Gly
805 810 815
Thr Pro Arg Pro Leu Gln Ile Val Lys Arg His Gly Ser Thr Asp Leu
820 825 830
Asp Thr Leu Ala Glu Gln Thr Tyr Trp Leu Ser Glu Ala His Val Gly
835 840 845
Ser Leu Ser Arg Ser Thr Arg Leu Pro Ile Thr Thr Tyr Tyr Ala Asp
850 855 860
Lys Cys Ala Asp Phe Ala Met Lys Gly Tyr Leu Thr Lys Gly Ser Val
865 870 875 880
Ile Arg Gly Val Pro Tyr Ile
885
<210> 6
<211> 847
<212> PRT
<213> artificial sequence
<400> 6
Met Pro Thr Gln Ser Asp Ile Glu Asp Gly Glu Arg Ile Asp Ile Gln
1 5 10 15
Val Lys Val Leu Ser Glu Leu Asp Arg Pro Ser Glu Lys Met Ala Lys
20 25 30
Arg Leu Arg Val Arg Asp Thr Asp Gly Asn Glu Phe Pro Leu Thr Ile
35 40 45
Trp Lys Asn Asn Ala Leu Cys Asp Phe Ala Trp Glu Arg Gly Arg Trp
50 55 60
Tyr Glu Leu Glu Asn Ala Arg Gly Asn Glu Phe Arg Gly Glu Lys Ser
65 70 75 80
Leu Asn Gly Ser Ser Arg Leu His Ala Asp Pro Val Asp Asn Pro Ile
85 90 95
Asp Ser Asp Arg Ser Gln Gln Ser Thr Thr Ala Glu Ser Thr Asp Lys
100 105 110
Gln Phe Asp Ser Leu Glu Asp Gly Leu Pro Tyr Leu Ser Leu Phe Pro
115 120 125
Ile Asp Arg Glu Phe Glu Thr Val Asp Val Tyr Glu Tyr Arg Ile Glu
130 135 140
Ala Asp Gly Pro Phe Asp Asp Asp Pro Met Asp Ala Thr Tyr Thr Leu
145 150 155 160
Ala Ala Tyr Leu Arg Ser Cys Ser Asp Ala Ala Val Thr His Ala Gly
165 170 175
Ile Phe Ser Val Ile Ala Thr Asn Arg Leu Thr Asn Ala Leu Pro Asp
180 185 190
Pro Phe Glu Leu Thr Asp Glu Ser Arg Val Thr Leu Arg Ala Asp Asp
195 200 205
Glu Thr Asp Asn Glu Cys Leu Val Arg Leu Leu Gln Gln Val Phe Lys
210 215 220
Thr Ala Val Asp Asp Glu Thr Tyr Glu Thr Gly Arg Val Asp Arg Ile
225 230 235 240
Arg Thr Gln Asp Pro Val Ile Thr Gly Gln Asp Gly Leu Phe Glu Ala
245 250 255
Cys Leu Ala Tyr Thr Ala Arg Leu Glu Ile Leu Pro Ser Gly Lys Ala
260 265 270
Phe Val Gly Ile Asp Ile Ser Tyr His Ala Arg Ser Gln Val Thr Val
275 280 285
Asp Lys Tyr Val Asp Arg Ile Asn Ala Ser Val Asp Glu Leu Ile Asp
290 295 300
Thr Pro Val Glu His Asp Pro Glu Arg Tyr Glu Lys Ser Gly Ser Gly
305 310 315 320
Arg Leu Lys Gly Phe Ala Asp Val Thr Phe Thr Asp Pro Val Asp Asp
325 330 335
Phe Gly Asn Gln Ser Leu Ala Asp Trp Tyr Glu Gln Lys Gly Arg Ile
340 345 350
Ser Asp Asp Met Leu Glu Arg Leu Arg Ser Glu Asp Pro Gln Leu Val
355 360 365
Glu Ile Gln Tyr Asn Pro Asn Ser Asp Glu Thr Asn Leu His Val Pro
370 375 380
Gln Leu Leu Arg Val Ala Pro Arg Lys Glu Ile Val Lys Lys Leu Ala
385 390 395 400
Pro Thr Phe His Arg Lys Trp Asp Arg Ala Ala Lys Met Leu Pro Asp
405 410 415
Asp Arg Phe Arg Lys Ala Thr Arg Phe Val Ala Arg Leu Asp Ser Leu
420 425 430
Ser Glu Val Asp Ala Gln Ile Glu Pro Asn Pro Val Gly Pro Asn Ile
435 440 445
Ser Phe Met Ser Thr Glu Val Asp Arg Ser Asp Asn Leu Arg Phe Gly
450 455 460
Asp Asp Gln Thr Thr Thr Leu Pro Asn Asn Gly Leu Lys Arg Tyr Gly
465 470 475 480
Ile Tyr Arg Arg Pro Ser Ser Leu His Leu His Tyr Leu Val Pro Glu
485 490 495
Arg Tyr Thr Asp Glu Phe Ala Ser Phe Arg Glu Gln Leu Glu Arg Gln
500 505 510
Leu Ala Thr Ile Gly Cys Ser Pro Asp Asp Ile Ser Tyr Asp Glu Tyr
515 520 525
Gly Leu Gly Asn Ala Ile Asn Tyr Asn Thr Thr Ala Ala Ala Val Asp
530 535 540
Asp Val Asp Ile Val Leu Ala Val Val Pro Ala Pro Asp Asn Asp Phe
545 550 555 560
Ile Arg Asn Gly Thr Ile Asp Asp Pro Tyr Pro Glu Phe Lys Lys Ser
565 570 575
Leu Gly Lys Gln Thr Ile Pro Ser Gln Met Val Arg Glu Asp Asn Leu
580 585 590
Asp Asp Arg Trp Ile Leu Arg Asn Thr Ala Leu Gly Val Ile Ala Gly
595 600 605
Ala Gly Gly Val Pro Trp Arg Val Asp Glu Met Pro Gly Asp Val Asp
610 615 620
Cys Phe Val Gly Leu Asp Ala Thr Arg Asp Pro Glu Thr Gly Gln Phe
625 630 635 640
Leu Gly Ala Ser Ala Asn Val Val Leu Ser Asp Gly Thr Val Phe Val
645 650 655
Ser Lys Thr Gln Ser Leu Gln Ser Gly Glu Thr Phe Asp Glu Asn Ala
660 665 670
Ile Val Asp Val Leu Lys Asp Val His Arg Glu Phe Val Arg Glu Glu
675 680 685
Gly Lys Ser Pro Asn Asn Ile Val Ile His Arg Asp Gly Arg Leu Phe
690 695 700
Glu Asp Val Asp Thr Ile Leu Glu Pro Phe Asp Glu Thr Asp Ile Asp
705 710 715 720
Ile Asp Ile Leu Asp Val Arg Lys Ser Gly Ala Pro Arg Ala Ala Val
725 730 735
Tyr Gln Asp Asp Gln Phe Gln Val Asp His Lys Gly Arg Leu Phe Val
740 745 750
Ala Gln Ser Gly Asp Tyr Gly Phe Leu Thr Thr Thr Gly Arg Pro Glu
755 760 765
Phe Asp Glu Asp Asp Gly Leu Gly Thr Pro Arg Ser Leu Arg Ile Val
770 775 780
Arg Arg Ala Gly Glu Thr Pro Met Arg Thr Leu Leu Glu Gln Val Tyr
785 790 795 800
Trp Leu Ser Glu Ser His Val Gly Ser Ala Gln Arg Ser Thr Arg Leu
805 810 815
Pro Ile Thr Thr Tyr Tyr Ala Asp Arg Cys Ala Glu His Ala Arg Glu
820 825 830
Gly Tyr Leu Val Asn Gly Glu Leu Ile Arg Gly Val Pro Tyr Leu
835 840 845
<210> 7
<211> 894
<212> PRT
<213> artificial sequence
<400> 7
Ala Val Lys Ala Asp Ile Glu Asp Gly Glu Glu Ile Asp Ile Ala Leu
1 5 10 15
His Val Thr Gly Ile Asp Glu Trp Glu His Asp Ala Ile Ala Arg Lys
20 25 30
Ile Gln Leu Glu Asp Val Asp Gly Ala Ala Ile Asp Leu Thr Val Phe
35 40 45
His Asn Asn Asp Val Ser Asp Phe Glu Trp Glu Ile Gly Glu Trp Tyr
50 55 60
Leu Leu Glu Asn Val Val Gly Asn Glu Phe Arg Gly Glu Met Gln Leu
65 70 75 80
Asn Pro Gly Tyr Asp Leu Thr Val Thr Leu Leu Asn Asp Pro Pro Ala
85 90 95
Ala Ala Gly Asn Asp Lys Ser Pro Gly Ser Val Pro Pro Glu Glu Pro
100 105 110
Val Asp Gln Ser Gly Glu Ser Gly Ser Ser Gly Ala Ala Ala Ser Thr
115 120 125
Ser Gly Glu Pro Gly Asp Ala Glu Phe Val Arg Gly Ser Glu Val Asp
130 135 140
Asp Gly Ser Arg Pro Thr Ala Asp Gly Gly Gly Lys Leu Leu His Gln
145 150 155 160
Gln Pro Leu Ser Asp Gly Asn Tyr Leu Leu Gln Phe Glu Leu Gly Ser
165 170 175
Leu Pro Glu Leu Pro Val His Glu Tyr Glu Leu Arg Ala Thr Gly Ser
180 185 190
Gly Gly Ile Asp Pro Asp Asp Phe Thr Asn Gly Ile Glu Gly Phe Thr
195 200 205
Ala Lys Ala Ala Asn Tyr Tyr Gln Ser Arg Ile Gly Ser Pro Val Thr
210 215 220
Thr Ala Asp Ala Ser Arg Arg Arg Ile Tyr Ala Thr Glu Lys Leu His
225 230 235 240
Gly Thr Ile Ser Met His Gly Tyr Thr Val Lys Pro Val His Gln Gly
245 250 255
Glu Thr Thr Leu Glu Ala Arg Ser Tyr Thr Asn Asp Gly Pro Leu Gln
260 265 270
Glu Phe Val Lys Gln Asp Val Lys Arg Ala Val Ala Gly Arg Phe Glu
275 280 285
Val Ser Gly Ile Asp Ser Ile Ile Glu Pro Thr Pro Gln Arg Thr Ala
290 295 300
Asn Ser Gly Leu Phe Glu Ala Tyr Arg Lys Tyr Lys Cys Arg Ile Arg
305 310 315 320
Val Asp Ala Asp Gly Thr Val Ile Cys Gly Val Asn Val Ala Tyr His
325 330 335
Leu Glu Ser Thr Phe Ser Ala Ala Glu Trp Val Gln Arg Gly His Asp
340 345 350
Ile Ala Asp Val Thr Val Glu His Asp Thr Asp Leu Tyr Asp Ser Ala
355 360 365
Arg Thr Ala Thr Val Lys Glu Ile Ile Asp Met Asp Tyr Asp Asp Met
370 375 380
Leu Asp Gly Pro Gly Val Pro Met Ser Glu Tyr His Glu Lys His Val
385 390 395 400
Glu Gln Asp Val Ile Asp Ser Met Arg Ala Gly Asn Pro Val Ile Ala
405 410 415
Asp Leu Gln Tyr Gly Ser Gly Glu Asp Ser Ile Phe Pro Gln Leu Leu
420 425 430
Glu Tyr Cys Lys Val Ile Pro Thr Phe Asp Gln Leu Gly Arg Val Asp
435 440 445
Glu Thr Phe Leu Asn Val Ile His Asn Glu Ser Arg Met Lys Pro Glu
450 455 460
Glu Arg Phe Asn Val Val Thr Ser Phe Val Asp Leu Leu Gly Pro Thr
465 470 475 480
Pro Tyr Phe Asp Phe Gly Pro Val Pro Gln Pro Thr Asn Ala Gly Tyr
485 490 495
Arg Glu Gln Lys Thr Pro Asn Ile Pro Asn Leu Arg Phe Gly Asp Gly
500 505 510
Arg Thr Gly Tyr Tyr Gly Ala Gly Gly Leu Glu Arg Lys Gly Tyr Gly
515 520 525
Val Tyr Lys Ala Pro Glu Ser Phe Asp Ile Ile Ala Leu Tyr Pro Asp
530 535 540
Ser Glu Gln Ala Ala Ala Arg Pro Tyr Val Leu Ser Val Leu Gly Lys
545 550 555 560
Leu Ala Glu Tyr Asp Gly Lys Pro Thr Lys Phe Asp Gln Glu Thr Tyr
565 570 575
Glu Leu Gly Ser Glu Phe His Tyr Ser Gln His Ala Gln Lys Thr Ser
580 585 590
Asp Tyr Asp Ala Ala Leu Ile Val Val Pro Asp Lys Asp Lys Ala Ala
595 600 605
Ala Ala Asp Tyr Asp Asp Pro Tyr Pro Glu Phe Lys Arg Arg Leu Gly
610 615 620
Gln Leu Gly Val Pro Ser Gln Met Ile Thr Ile Asp Asn Leu Gly Asn
625 630 635 640
Asp Ser Tyr Leu Gly Asn Ile Ser Ser Ser Leu Ile Gly Lys Ala Gly
645 650 655
Gly Val Pro Trp Arg Ile Asp Asp Val Pro Gly Asp Val Asp Ala Phe
660 665 670
Val Gly Leu Asp Val Thr Tyr Asp His Ala Thr Lys Gln His Leu Gly
675 680 685
Ala Ala Ala Asn Val Ile Met Ala Asp Gly Thr Ile Leu Ala Ser Glu
690 695 700
Ala Val Thr Lys Gln Ala Gly Glu Thr Phe Asp Glu Asp Asp Val Ala
705 710 715 720
Asn Val Ile Lys His Val Leu Glu Ile Phe Ala Glu Glu Glu Gly Arg
725 730 735
Pro Pro Arg His Val Val Ile His Arg Asp Gly Lys Phe Tyr Leu Asp
740 745 750
Ile Glu Ser Leu Ile Lys Arg Leu Asp Lys Ala Arg Asp Leu Ile Gln
755 760 765
Arg Phe Asp Leu Val Glu Ile Arg Lys Ser Gly Asn Pro Arg Ile Ala
770 775 780
Glu Tyr Asp Glu Ser Lys Ser Arg Phe Asp Ile Ala Asp Lys Gly Val
785 790 795 800
Ala Phe His Val His Asn Gly Asp His Ser Tyr Leu Thr Thr Thr Gly
805 810 815
Gly Lys Glu Gly Ser Pro Gly Thr Pro Arg Pro Leu Gln Ile Val Lys
820 825 830
Arg His Gly Ser Thr Asp Leu Asp Thr Leu Ala Glu Gln Thr Tyr Trp
835 840 845
Leu Ser Glu Ala His Val Gly Ser Leu Ser Arg Ser Thr Arg Leu Pro
850 855 860
Ile Thr Thr Tyr Tyr Ala Asp Lys Cys Ala Asp Phe Ala Met Lys Gly
865 870 875 880
Tyr Leu Thr Lys Gly Ser Val Ile Arg Gly Val Pro Tyr Ile
885 890
<210> 8
<211> 833
<212> PRT
<213> artificial sequence
<400> 8
Ser Pro Lys Ser Lys Gln Ala Thr Ile Leu Glu Phe Leu Ser Val Lys
1 5 10 15
Gly Lys Asp Lys Gln Gln Lys Thr Ile Lys Ser Gln Pro Leu Met Lys
20 25 30
Ser Ser Glu Pro Glu Glu Glu Ser Phe Pro Leu Val Glu Val Asp Ser
35 40 45
Glu Trp Asn Ile Ile Arg Ile Asn Pro Glu Ile Ala Lys Ser Leu Phe
50 55 60
Ala Lys Thr Val Lys Thr Tyr Tyr Gly Leu Gly Lys Asn Tyr Val Ala
65 70 75 80
Glu Asn Leu Leu His Asp Glu Glu Lys Val Glu Phe Leu Arg Arg Val
85 90 95
Tyr Glu Leu Phe Pro Tyr Asn Tyr Leu Ala Lys Ser Glu Asn Gly Ile
100 105 110
Pro Tyr Tyr Glu Tyr Tyr Ser Thr Ala Glu Asn Ile Asp Ala Asp Ile
115 120 125
Val Asp His Leu Gln Leu Ile Lys Ile Gly Glu Tyr His Trp Glu Glu
130 135 140
Leu Asp Pro His Ile Ala Val Arg Leu Ile Thr Ala His Ile Arg Ser
145 150 155 160
Ser Phe Gly Glu Phe Leu Lys Asn Lys Leu Ser Ser Arg Glu Leu Lys
165 170 175
Asp Val Trp Ile Arg Leu Pro Lys Gly Arg Glu Arg Val Ser Leu Glu
180 185 190
Phe Val Lys Lys Phe Glu Leu Gly Thr Leu Gly Tyr Ser Ile Glu Asp
195 200 205
Gly Glu Ile Trp Met Ala Leu Arg Arg Arg Ser Ser Ala Ser Ala Val
210 215 220
Leu Leu Ala Asp Phe Pro Pro Lys Val Leu Glu Tyr Val Met Ile Lys
225 230 235 240
Leu Lys Lys Leu Ala Glu Glu Ala Val Lys Gln Asp Tyr Arg Lys Val
245 250 255
Arg Ile Tyr Ser Glu Thr Gln Pro Gly Ser Gly Thr Ala Ala Val Ile
260 265 270
Asp Val Ile Ile Gly His Asp Asn Val Ile Arg Phe Leu Glu Glu His
275 280 285
Pro Lys Gly Ala Phe His Val Lys Lys Arg Leu Glu Glu Leu Gly Lys
290 295 300
Ser Leu Asp Asp Val Asn Tyr Leu Leu Ile Gly Val Tyr Asp Asn Ser
305 310 315 320
Ile Ser Leu Lys Arg Ala Leu Glu Asp Glu Asn Cys Gln Tyr Tyr Phe
325 330 335
Thr Glu His Asn Ala Tyr Leu Val Leu Thr Thr Glu Val Gln Lys Glu
340 345 350
Leu Phe Gly Arg Ile Val Asp Asp Trp Arg Gly Glu Ile Val Glu Glu
355 360 365
Tyr Arg Glu Lys Leu Asn Glu Ile Thr Thr Ser Gly Lys Leu Phe Ser
370 375 380
Gln Val Ser Gly Ile Lys Gly Ile Thr Val Asn Ile Arg Glu Asn Leu
385 390 395 400
Leu Val Arg Thr Leu Lys Gly Glu Ile Thr Val Lys Asp Val Lys Asp
405 410 415
Ile Met Arg Asp Glu Ser Ile Phe Leu Asn Leu Leu Pro Ile Ser Glu
420 425 430
Lys Ile Leu Asn Glu Thr Lys Arg His Asn Leu Arg Leu Leu Ile Phe
435 440 445
Tyr Pro Lys Lys Phe Asp Glu Arg Ile Arg Lys Ser Ile Phe Leu Asp
450 455 460
Gln Ile Glu Arg Leu Arg Asn Gly Leu Leu Ser Asn Ser Phe Ser Ser
465 470 475 480
Val Asp Glu Val Asp Leu Ile Pro Val Ser Arg Asp Arg Ser Leu Asp
485 490 495
Tyr His Lys Thr Met Leu Glu Ala Gly Leu Asp Lys Val Arg Asp Tyr
500 505 510
Thr Leu Ala Thr Ile Ile Phe Pro Glu Gln Tyr Asn Lys Arg Asp Leu
515 520 525
Glu Leu Arg Glu Phe Tyr Asn Trp Leu Lys Lys Glu Phe Tyr Asp Glu
530 535 540
Thr Lys Pro Leu Val Phe Gln Gly Ala Arg Val Glu Ser Val Phe Gly
545 550 555 560
Met Tyr Lys Arg Tyr Ala Val Pro Asn Ile Val Leu Gln Met Ala Ala
565 570 575
Lys Leu Gly Val Tyr Pro Tyr Ser Leu Glu Thr Ser Ser Gly Tyr Asp
580 585 590
Tyr Ile Ile Gly Ile Asp Tyr Thr Tyr Trp His Glu Arg Asp Ala Val
595 600 605
Ser Val Gly Gly Gly Ala Val Val Val Ser Pro Ser Gly Leu Ile Glu
610 615 620
Gly Ile Tyr Pro Ile Ala Ile Pro Ser Lys Arg Glu Ser Leu Asp Met
625 630 635 640
Lys Glu Ile Leu Gln Glu Trp Phe Leu Lys Thr Val Gln Asn Asn Pro
645 650 655
Glu Ile Met Lys Gln Gly Arg Val Thr Val Leu Ile Ser Arg Asp Gly
660 665 670
Met Val Pro Lys Tyr Glu Arg Asn Arg Ile Gln Glu Phe Leu Cys Glu
675 680 685
Tyr Ser Asp Glu Leu Asp Met Thr Ile Glu Ala Val Glu Val Arg Lys
690 695 700
Arg Ile Leu Thr Arg Ile Trp Ser Leu Asp Gly Pro Asn Thr Phe Tyr
705 710 715 720
Ser Pro Val Lys Val Gly Asn Tyr Thr Tyr Tyr Met Val Asn Ala His
725 730 735
Ala Gly Tyr Pro Leu Arg Arg Lys Glu Arg Lys Ile Tyr Tyr Ser Lys
740 745 750
Pro Tyr Leu Ile Gly Ser Leu Tyr Arg Phe Gln Ser Gly Lys Val Gln
755 760 765
Pro Ile His Gly Ser Ala Ser Arg His Leu Val Glu Ser Leu Ile Arg
770 775 780
Leu Gln Lys Ile Asn Tyr Thr Thr Thr Lys Met Asp Asn Val Arg Leu
785 790 795 800
Pro Leu Pro Ile Asp Val Thr His Lys Leu Ile Asn Phe Ile Arg Asp
805 810 815
Val Asn Met Arg Val Lys Arg Val Gly Ile Pro Asn Ser Leu Phe Met
820 825 830
Ala
<210> 9
<211> 755
<212> PRT
<213> artificial sequence
<400> 9
Pro Arg Glu Thr Cys Tyr Asp Lys Arg Thr Thr Pro Ser Gln Tyr Gly
1 5 10 15
Trp Leu Pro Ile Asp Ser Leu Ser Val Met Pro Thr Gln Phe Gln Glu
20 25 30
Val Glu Val Ile Leu Asn Arg Phe Phe Val Lys Lys Leu Ser Arg Pro
35 40 45
Asp Leu Thr Phe His Glu Tyr Gln Cys Gln Phe Thr Gln Val Pro Glu
50 55 60
Gln Gly Ser Glu Gln Lys Ala Ile Ser Ser Val Cys Tyr Lys Leu Gly
65 70 75 80
Val Thr Ala Val Arg Leu Gly Ser Cys Ile Ile Thr Arg Glu Pro Ile
85 90 95
Asp Pro Glu Arg Met Arg Thr Lys Asp Trp Gln Leu Gln Leu Ile Gly
100 105 110
Cys Arg Glu Leu Ser Cys Gln Asn Tyr Arg Glu Arg Gln Ala Leu Glu
115 120 125
Thr Phe Glu Arg Lys Ile Leu Glu Glu Lys Leu Lys Glu Thr Phe Lys
130 135 140
Lys Thr Ile Ile Glu Lys Asp Tyr Glu Leu Gly Leu Ile Trp Trp Ile
145 150 155 160
Ser Gly Glu Glu Gly Leu Glu Lys Thr Gly His Gly Trp Glu Val His
165 170 175
Arg Gly Arg Gln Ile Asp Leu Lys Ile Glu Thr Asp Glu Lys Leu Tyr
180 185 190
Leu Glu Ile Asp Ile His His Arg Phe Tyr Thr Pro Phe Lys Leu Glu
195 200 205
Trp Trp Leu Ser Glu Tyr Pro Asn Ile Gln Ile Lys Tyr Val Arg Asn
210 215 220
Thr Tyr Lys Asp Lys Lys Lys Trp Ile Leu Glu Asn Phe Ala Asp Lys
225 230 235 240
Ser Pro Asn Glu Ile Gln Ile Glu Ala Leu Gly Ile Ser Leu Ala Glu
245 250 255
Tyr His Arg Gln Glu Gly Ala Thr Gln Gln Glu Ile Asp Glu Ser Arg
260 265 270
Val Val Ile Val Lys Lys Ile Ser Asp Tyr Lys Ala Lys Pro Val Tyr
275 280 285
His Leu Ser Gln Arg Leu Ser Pro Ile Leu Thr Met Glu Thr Leu Ala
290 295 300
Gln Ile Ala Glu Gln Gly Arg Glu Lys Lys Glu Ile Gln Gly Val Phe
305 310 315 320
Asp Tyr Ile Arg Lys Asn Ile Gly Thr Arg Leu Gln Glu Ser Gln Lys
325 330 335
Ile Ala Gln Val Ile Phe Lys Asn Val Tyr Asn Leu Ser Ser Gln Pro
340 345 350
Glu Ile Met Lys Val Asn Gly Phe Val Met Pro Arg Ala Lys Leu Leu
355 360 365
Ala Arg Asn Asn Lys Glu Val Asn Gln Thr Ala Arg Ile Lys Ser Phe
370 375 380
Gly Cys Ala Lys Ile Gly Glu Thr Lys Phe Gly Cys Leu Asn Leu Phe
385 390 395 400
Asp Asn Lys Pro Glu Tyr Pro Glu Glu Val His Lys Cys Leu Leu Ala
405 410 415
Ile Ala Arg Ser Ser Gly Val Gln Ile Lys Ile Asp Ser Tyr Phe Thr
420 425 430
Gly Ser Asp Tyr Pro Lys Asp Asp Leu Ala Gln Gln Arg Phe Trp Gln
435 440 445
Gln Trp Ala Ala Gln Gly Ile Lys Thr Val Leu Val Val Met Pro Trp
450 455 460
Ser Pro His Glu Glu Lys Thr Arg Leu Arg Ile Gln Ala Leu Lys Ala
465 470 475 480
Gly Ile Ala Thr Gln Phe Met Ile Pro Thr Pro Gln Asp Asn Pro Tyr
485 490 495
Lys Ala Leu Asn Val Ala Leu Gly Leu Leu Cys Lys Ala Lys Trp Gln
500 505 510
Pro Val Tyr Leu Lys Pro Leu Asp Asp Pro Gln Ala Ala Asp Leu Ile
515 520 525
Ile Gly Phe Asp Thr Ser Thr Asn Arg Arg Leu Tyr Tyr Gly Thr Ser
530 535 540
Ala Phe Ala Ile Leu Ala Asn Gly Gln Ser Leu Gly Trp Glu Leu Pro
545 550 555 560
Asp Ile Gln Arg Gly Glu Thr Phe Ser Gly Gln Ser Ile Trp Gln Val
565 570 575
Val Ser Lys Leu Val Leu Lys Phe Gln Asp Asn Tyr Asp Ser Tyr Pro
580 585 590
Lys Lys Ile Leu Leu Met Arg Asp Gly Leu Val Gln Asp Gly Glu Phe
595 600 605
Glu Gln Thr Ile Arg Glu Leu Thr His Gln Gly Ile Asp Val Asp Ile
610 615 620
Leu Ser Val Arg Lys Ser Gly Ser Gly Arg Met Gly Arg Glu Leu Thr
625 630 635 640
Ser Gly Asn Thr Ala Ile Thr Tyr Asp Asp Ala Glu Val Gly Thr Val
645 650 655
Ile Phe Tyr Ser Ala Thr Asp Ser Phe Ile Leu Gln Thr Thr Glu Val
660 665 670
Ile Lys Thr Lys Thr Gly Pro Leu Gly Ser Ala Arg Pro Leu Arg Val
675 680 685
Val Arg His Tyr Gly Asn Thr Pro Leu Glu Leu Leu Ala Leu Gln Thr
690 695 700
Tyr His Leu Thr Gln Leu His Pro Ala Ser Gly Phe Arg Ser Cys Arg
705 710 715 720
Leu Pro Trp Val Leu His Leu Ala Asp Arg Ser Ser Lys Glu Phe Gln
725 730 735
Arg Ile Gly Gln Ile Ser Leu Leu Gln Asn Val Asp Arg Glu Lys Leu
740 745 750
Ile Ala Val
755
<210> 10
<211> 717
<212> PRT
<213> artificial sequence
<400> 10
Gln Ala Glu Ile Asp Asp Ala Phe Ala Asp Val Pro Glu Ser Ala Thr
1 5 10 15
Glu Gln Thr Gly His Ala Leu Thr Thr Phe Arg Ser Glu Lys Ser Leu
20 25 30
Ser Glu Phe Ala Val His Glu Tyr Thr Leu Lys Ala Lys Asp Gly Tyr
35 40 45
Arg Pro Asp Asp His Gln Ala Ala Leu Arg Asp Thr Tyr Lys Ala Arg
50 55 60
Arg Asp Ile Leu Gly Glu Phe Glu Ser Ser Ser Pro Pro Val Ile Ala
65 70 75 80
Val Arg Asp Ala Leu Ala Leu Ala Thr Pro Ser Pro Leu Pro Val Glu
85 90 95
Asp Leu Glu Leu Lys Asn Phe Glu Met Val Asn Asp Gly Pro His Thr
100 105 110
Leu Asp Tyr Thr Asp Tyr Ser Asp Lys Ala Val Thr Lys Gly Leu Ile
115 120 125
Asp Ala Ser Leu Arg Arg Ile Leu Asp Gly Asp Tyr Glu Val Arg Gly
130 135 140
Ile Asp Thr Val Leu Ser Lys Arg Pro Val Ile Gln Lys Gln Asp Phe
145 150 155 160
Arg Leu His Glu Arg Trp Asn Leu Ser Leu Ser Val Thr Asn Ala Gly
165 170 175
Val Val Tyr Leu Ser Val Asp Phe Arg His Lys Thr Ile Ser Glu Tyr
180 185 190
Thr Leu Asp Lys Phe Asp Leu Asp Lys Leu Tyr Arg Gly Leu Arg Val
195 200 205
Asn Val Thr Tyr Lys Gln Ser Gly Lys Gly Ala Phe Val Asp Glu Leu
210 215 220
Met Asp Lys Thr Val Asn Glu Ser Ile Asp Asp Met Gly Asn Gln Ser
225 230 235 240
Val Val Glu Tyr His Glu Gly Ala Glu Arg Ile Pro Asp Arg Val Leu
245 250 255
Lys Glu Ile Ala Arg Ala Asp Arg Arg Val Val Lys Val Thr Lys Gln
260 265 270
Gly Ser His Asn Thr Glu Tyr Tyr Pro Gln Arg Leu Leu Ala Leu Gln
275 280 285
Gly His Pro Gln Asn Val Lys Ala Phe Ala Pro Arg Phe Asn Glu Ala
290 295 300
Thr Arg Gly Lys Thr Arg Leu Ser Ala Gln Arg Cys Leu Asn Arg Ala
305 310 315 320
Thr Thr Phe Val Glu Asn Leu Pro Pro Val Ile Pro Leu Gly Gly Ala
325 330 335
Thr Leu Ser Phe Asp Ala Thr Pro Val Asn Gly Asp Asp Thr Trp Glu
340 345 350
Met Ser Arg Leu Phe Glu Thr Asp Ala His Ile Leu Gln Phe Ala Glu
355 360 365
Glu Gln Thr Gly Asp His Pro Arg Arg Val Lys His Asn Glu Val Tyr
370 375 380
Glu Ala Pro Glu Glu Phe Ser Val Cys Leu Val His Pro Ser Ala Gly
385 390 395 400
Pro His Ala Glu Arg Trp Glu Asn Leu Asp Gln Gln Leu Lys Asp Ile
405 410 415
Gly Ala Gly Pro Glu Ala Val Asn Arg Val Gln Tyr Asp Pro Phe Lys
420 425 430
Thr Ala Asp Glu Ile Tyr Thr Asp Leu Leu Val Asp Val Pro Asp Asp
435 440 445
His Glu Tyr Ser Ala Ala Cys Val Ile Leu Pro Lys Ala Asp Phe Ser
450 455 460
Met Gly Glu Ser Ser Ala Ser Asp Ile Tyr His Glu Met Lys Lys Ala
465 470 475 480
Leu Arg Gln Arg Arg Val Asp Ser Gln Met Ala His Ile Asp Thr Leu
485 490 495
Ala Thr Ser Tyr Ala Leu Pro Asn Val Ala Leu Gly Leu Val Ala Ala
500 505 510
Ala Gly Gly Ile Pro Phe Thr Thr Glu Asp Ala Met Pro Gly Glu Thr
515 520 525
Asp Leu Phe Ile Gly Ile Asp Val Ser His Arg Tyr Pro Arg Asp Thr
530 535 540
Asp Glu Arg Val His Ile Ala Ala Ser Thr Thr Ser Ile Tyr Gly Asp
545 550 555 560
Gly Thr Ile Leu Gly Tyr Thr Ser Ala Lys Pro Gln Thr Gly Glu Lys
565 570 575
Val Pro Pro Lys Glu Leu Lys Asn Leu Thr Arg Gln Ser Ile Ala Gly
580 585 590
Tyr Lys Gln Glu His Gly Glu Tyr Pro Asp Arg Ile Val Ile His Arg
595 600 605
Asp Gly Phe Met Arg Glu Asp Leu Asp Gln Val Glu Glu Met Leu Glu
610 615 620
Ser Met Asp Ile Asn Tyr Asp Val Val Glu Ile Arg Lys Gln Ser Pro
625 630 635 640
Ala Arg Val Leu Asn Leu Ala Asp Gly Val Ala Lys Ile Pro Asp Lys
645 650 655
Gly Ile Ala Ala Leu Asn Arg Glu Glu Asn Arg Ala Ile Leu Ala Thr
660 665 670
Phe Gly Asp Pro Glu Ser Gln Ala Thr Ser Ser Asn Thr Gly Leu Pro
675 680 685
Gln Pro Ile Gln Val Glu Arg Lys Ala Gly Asp Thr Asp Ile Lys Thr
690 695 700
Leu Val Val Ser Gln Ser Pro Leu Glu Phe Ser Ser Asn
705 710 715
<210> 11
<211> 745
<212> PRT
<213> artificial sequence
<400> 11
Tyr Thr Glu Thr Lys Thr Ala Asn Ser Pro Ile Phe Leu Ser Glu Ile
1 5 10 15
Ser Ser Leu Thr Leu Asn Asn Asn Cys Leu Asn Cys Phe Lys Leu Asn
20 25 30
His Gln Val Thr Arg Lys Ile Gly Asn Arg Phe Ser Trp Gln Phe Ser
35 40 45
Arg Lys Phe Pro Ala Val Val Val Ile Phe Glu Asp Asn Cys Phe Trp
50 55 60
Val Leu Ala Lys Asp Glu Lys Leu Leu Pro Ser Pro Gln Gln Trp Lys
65 70 75 80
Glu Ala Leu Ser Asp Ile Gln Glu Val Leu Arg Glu Asp Ile Gly Asp
85 90 95
His Tyr Tyr Ser Ile His Trp Leu Lys Asp Phe Gln Ile Thr Ala Leu
100 105 110
Val Thr Ala Gln Leu Ala Val Arg Ile Leu Lys Ile Phe Gly Lys Phe
115 120 125
Ser Tyr Pro Ile Val Phe Pro Lys Asp Ser Gln Ile Ser Glu Asn Gln
130 135 140
Val Gln Val Arg Arg Glu Val Asn Phe Trp Ala Glu Ile Ile Asn Asp
145 150 155 160
Thr Asp Pro Ala Ile Cys Leu Thr Leu Glu Ser Ser Ile Val Tyr Ser
165 170 175
Gly Asp Leu Glu Gln Phe Tyr Glu Asn His Pro Tyr Arg Gln Asp Ala
180 185 190
Ala Lys Leu Leu Val Gly Leu Lys Val Lys Thr Ile Glu Thr Asn Gly
195 200 205
Thr Ala Lys Ile Ile Arg Ile Ala Gly Thr Ile Gly Glu Arg Arg Glu
210 215 220
Glu Leu Leu Thr Lys Ala Thr Gly Ser Ile Ser Arg Arg Lys Leu Glu
225 230 235 240
Glu Ala His Leu Gly Gln Pro Val Val Ala Val Gln Phe Gly Lys Asn
245 250 255
Ser Gln Glu Tyr Ile Tyr Pro Leu Ala Ala Leu Lys Pro Cys Met Thr
260 265 270
Asp Lys Asp Glu Ser Leu Phe Gln Val Asn Tyr Gly Glu Leu Leu Lys
275 280 285
Glu Thr Lys Ile Phe Tyr Ala Glu Arg Gln Glu Arg Leu Lys Leu Tyr
290 295 300
Lys Gln Glu Ala Gln Asn Thr Leu Asn Asn Phe Gly Phe Arg Leu Gly
305 310 315 320
Glu Lys Ser Ile Asn Ser Arg Glu Tyr Pro Glu Leu Phe Trp Asn Pro
325 330 335
Ser Ile Ser Leu Glu Gln Thr Pro Ile Leu Phe Gly Lys Gly Glu Arg
340 345 350
Gly Glu Lys Ile Lys Thr Leu Lys Gly Leu Ser Lys Gly Gly Val Tyr
355 360 365
Lys Arg His Arg Glu Tyr Leu Asp Pro Ala Arg Lys Ile Arg Leu Ala
370 375 380
Ile Leu Lys Pro Ala Asn Leu Lys Val Gly Asp Phe Arg Glu Gln Leu
385 390 395 400
Glu Lys Arg Leu Glu Leu Tyr Lys Phe Glu Thr Ile Leu Pro Ala Glu
405 410 415
Asn Gln Ile Asn Phe Ser Val Glu Gly Val Gly Phe Glu Lys Arg Ala
420 425 430
Arg Leu Glu Glu Ala Val Asp Gln Leu Ile Arg Gly Glu Ile Pro Val
435 440 445
Asp Ile Ala Leu Val Phe Leu Pro Gln Glu Asp Arg Asn Ala Asp Asn
450 455 460
Thr Glu Glu Gly Ser Leu Tyr Ser Trp Ile Lys Lys Lys Phe Leu Glu
465 470 475 480
Arg Arg Val Met Thr Gln Met Ile Tyr Glu Lys Thr Leu Asn Asp Lys
485 490 495
Ser Asn Tyr Lys Asn Ile Leu Asn Gln Val Val Pro Gly Ile Leu Ala
500 505 510
Lys Leu Gly Asn Leu Pro Tyr Val Leu Ala Glu Ser Leu Glu Ile Ala
515 520 525
Asp Tyr Phe Ile Gly Leu Asp Val Gly Arg Met Pro Lys Lys Asn Leu
530 535 540
Pro Gly Ser Leu Asn Val Cys Ala Ser Val Arg Leu Tyr Gly Lys Gln
545 550 555 560
Gly Glu Phe Val Arg Cys Arg Val Glu Asp Ser Leu Thr Glu Gly Glu
565 570 575
Glu Ile Pro Gln Arg Ile Leu Glu Asn Cys Leu Pro Gln Ala Glu Leu
580 585 590
Lys Asn Gln Thr Val Leu Ile Tyr Arg Asp Gly Lys Phe Gln Gly Lys
595 600 605
Glu Val Asp Asn Leu Leu Ala Arg Ala Arg Ala Ile Asn Ala Lys Phe
610 615 620
Ile Leu Val Glu Cys Tyr Lys Thr Gly Ile Pro Arg Leu Tyr Asn Phe
625 630 635 640
Glu Gln Lys Gln Ile Asn Ala Pro Ser Lys Gly Leu Ala Phe Ala Leu
645 650 655
Ser Lys Arg Glu Val Ile Leu Ile Thr Ser Gln Val Ser Glu Gln Ile
660 665 670
Gly Val Pro Arg Pro Leu Arg Leu Lys Val His Glu Leu Gly Asp Gln
675 680 685
Val Asn Leu Lys Gln Leu Val Asp Thr Thr Leu Lys Leu Thr Leu Leu
690 695 700
His Tyr Gly Ser Leu Lys Glu Pro Arg Leu Pro Ile Pro Leu Tyr Gly
705 710 715 720
Ala Asp Ala Ile Ala Tyr Arg Arg Leu Gln Gly Ile Cys Pro Ser Leu
725 730 735
Leu Glu Asp Asp Cys Gln Phe Trp Leu
740 745
<210> 12
<211> 733
<212> PRT
<213> artificial sequence
<400> 12
Leu Leu Ser Asn Leu Arg Arg Ser Ser Ile Val Leu Asn Arg Phe Tyr
1 5 10 15
Val Lys Ser Leu Ser Gln Ser Asp Leu Thr Ala Tyr Glu Tyr Arg Cys
20 25 30
Ile Phe Lys Lys Thr Pro Glu Leu Gly Asp Glu Lys Arg Leu Leu Ala
35 40 45
Ser Ile Cys Tyr Lys Leu Gly Ala Ile Ala Val Arg Ile Gly Ser Asn
50 55 60
Ile Ile Thr Lys Glu Ala Val Arg Pro Glu Lys Leu Gln Gly His Asp
65 70 75 80
Trp Gln Leu Val Gln Met Gly Thr Lys Gln Leu Asp Cys Arg Asn Asp
85 90 95
Ala His Arg Cys Ala Leu Glu Thr Phe Glu Arg Lys Phe Leu Glu Arg
100 105 110
Asp Leu Ser Ala Ser Ser Gln Thr Glu Val Arg Lys Ala Ala Glu Gly
115 120 125
Gly Leu Ile Trp Trp Val Val Gly Ala Lys Gly Ile Glu Lys Ser Gly
130 135 140
Asn Gly Trp Glu Val His Arg Gly Arg Arg Ile Asp Val Ser Leu Asp
145 150 155 160
Ala Glu Gly Asn Leu Tyr Leu Glu Ile Asp Ile His His Arg Phe Tyr
165 170 175
Thr Pro Trp Thr Val His Gln Trp Leu Glu Gln Tyr Pro Glu Ile Pro
180 185 190
Leu Ser Tyr Val Arg Asn Asn Tyr Leu Asp Glu Arg His Gly Phe Ile
195 200 205
Asn Trp Gln Tyr Gly Arg Phe Thr Gln Glu Arg Pro Gln Asp Ile Leu
210 215 220
Leu Asp Cys Leu Gly Met Ser Leu Ala Glu Tyr His Leu Asn Lys Gly
225 230 235 240
Ala Thr Glu Glu Glu Val Gln Gln Ser Tyr Val Val Tyr Val Lys Pro
245 250 255
Ile Ser Trp Arg Lys Gly Lys Leu Thr Ala His Leu Ser Arg Arg Leu
260 265 270
Ser Pro Ser Leu Thr Met Glu Met Leu Ala Lys Val Ala Glu Asp Ser
275 280 285
Thr Val Cys Asp Arg Glu Lys Arg Glu Ile Arg Ala Val Phe Lys Ser
290 295 300
Ile Lys Gln Ser Ile Asn Gln Arg Leu Gln Glu Ala Gln Lys Thr Ala
305 310 315 320
Ser Trp Ile Leu Thr Lys Thr Tyr Gly Ile Ser Ser Pro Ala Ile Ala
325 330 335
Leu Ser Cys Asp Gly Tyr Leu Leu Pro Ala Ala Lys Leu Leu Ala Ala
340 345 350
Asn Lys Gln Pro Val Ser Lys Thr Ala Asp Ile Arg Asn Lys Gly Cys
355 360 365
Ala Lys Ile Gly Glu Thr Ser Phe Gly Tyr Leu Asn Leu Tyr Asn Asn
370 375 380
Gln Leu Gln Tyr Pro Leu Glu Val His Lys Cys Leu Leu Glu Ile Ala
385 390 395 400
Asn Lys Asn Asn Leu Gln Leu Ser Leu Asp Gln Arg Arg Val Leu Ser
405 410 415
Asp Tyr Pro Gln Asp Asp Leu Asp Gln Gln Met Phe Trp Gln Thr Trp
420 425 430
Ser Ser Gln Gly Ile Lys Thr Val Leu Val Val Met Pro Trp Asp Ser
435 440 445
His His Asp Lys Gln Lys Ile Arg Ile Gln Ala Ile Gln Ala Gly Ile
450 455 460
Ala Thr Gln Phe Met Val Pro Leu Pro Lys Ala Asp Lys Tyr Lys Ala
465 470 475 480
Leu Asn Val Thr Leu Gly Leu Leu Cys Lys Ala Gly Trp Gln Pro Ile
485 490 495
Gln Leu Glu Ser Val Asp His Pro Glu Val Ala Asp Leu Ile Ile Gly
500 505 510
Phe Asp Thr Gly Thr Asn Arg Glu Leu Tyr Tyr Gly Thr Ser Ala Phe
515 520 525
Ala Val Leu Ala Asp Gly Gln Ser Leu Gly Trp Glu Leu Pro Ala Val
530 535 540
Gln Arg Gly Glu Thr Phe Ser Gly Gln Ala Ile Trp Gln Thr Val Ser
545 550 555 560
Lys Leu Ile Ile Lys Phe Tyr Gln Ile Cys Gln Arg Tyr Pro Gln Lys
565 570 575
Leu Leu Leu Met Arg Asp Gly Leu Val Gln Glu Gly Glu Phe Gln Gln
580 585 590
Thr Ile Glu Leu Leu Lys Glu Arg Lys Ile Ala Val Asp Val Ile Ser
595 600 605
Val Arg Lys Ser Gly Ala Gly Arg Met Gly Gln Glu Ile Tyr Glu Asn
610 615 620
Gly Gln Leu Val Tyr Arg Asp Ala Ala Ile Gly Ser Val Ile Leu Gln
625 630 635 640
Pro Ala Glu Arg Ser Phe Ile Met Val Thr Ser Gln Pro Val Ser Lys
645 650 655
Thr Ile Gly Ser Ile Arg Pro Leu Arg Ile Val His Glu Tyr Gly Ser
660 665 670
Thr Asp Leu Glu Leu Leu Ala Leu Gln Thr Tyr His Leu Thr Gln Leu
675 680 685
His Pro Ala Ser Gly Phe Arg Ser Cys Arg Leu Pro Trp Val Leu His
690 695 700
Leu Ala Asp Arg Ser Ser Lys Glu Phe Gln Arg Ile Gly Gln Ile Ser
705 710 715 720
Val Leu Gln Asn Ile Ser Arg Asp Lys Leu Ile Ala Val
725 730
<210> 13
<211> 744
<212> PRT
<213> artificial sequence
<400> 13
Ser Asn Leu Thr Val Glu Ala Phe Glu Gly Ile Gly Ser Val Asn Pro
1 5 10 15
Met Leu Phe Tyr Gln Tyr Lys Val Thr Gly Lys Gly Lys Tyr Asp Asn
20 25 30
Val Tyr Lys Ile Ile Lys Ser Ala Arg Tyr Lys Met His Ser Lys Asn
35 40 45
Arg Phe Lys Pro Val Phe Ile Lys Asp Asp Lys Leu Tyr Thr Leu Glu
50 55 60
Lys Leu Pro Asp Ile Glu Asp Leu Asp Phe Ala Asn Ile Asn Phe Val
65 70 75 80
Lys Ser Glu Val Leu Ser Ile Glu Asp Asn Met Ser Ile Tyr Gly Glu
85 90 95
Val Val Glu Tyr Tyr Ile Asn Leu Lys Leu Lys Lys Val Lys Val Leu
100 105 110
Gly Lys Tyr Pro Lys Tyr Arg Ile Asn Tyr Ser Lys Glu Ile Leu Ser
115 120 125
Asn Thr Leu Leu Thr Arg Glu Leu Lys Asp Glu Phe Lys Lys Ser Asn
130 135 140
Lys Gly Phe Asn Leu Lys Arg Lys Phe Arg Ile Ser Pro Val Val Asn
145 150 155 160
Lys Met Gly Lys Val Ile Leu Tyr Leu Ser Cys Ser Ala Asp Phe Ser
165 170 175
Thr Asn Lys Asn Ile Tyr Glu Met Leu Lys Glu Gly Leu Glu Val Glu
180 185 190
Gly Leu Ala Val Lys Ser Glu Trp Ser Asn Ile Ser Gly Asn Leu Val
195 200 205
Ile Glu Ser Val Leu Glu Thr Lys Ile Ser Glu Pro Thr Ser Leu Gly
210 215 220
Gln Ser Leu Ile Asp Tyr Tyr Lys Asn Asn Asn Gln Gly Tyr Arg Val
225 230 235 240
Lys Asp Phe Thr Asp Glu Asp Leu Asn Ala Asn Ile Val Asn Val Arg
245 250 255
Gly Asn Lys Lys Ile Tyr Met Tyr Ile Pro His Ala Leu Lys Pro Ile
260 265 270
Ile Thr Arg Glu Tyr Leu Ala Lys Asn Asp Pro Glu Phe Ser Lys Glu
275 280 285
Ile Glu Gln Leu Ile Lys Met Asn Met Asn Tyr Arg Tyr Glu Thr Leu
290 295 300
Lys Ser Phe Val Asn Asp Ile Gly Val Ile Glu Glu Leu Asn Asn Leu
305 310 315 320
Ser Phe Lys Asn Lys Tyr Tyr Glu Asp Val Lys Leu Leu Gly Tyr Ser
325 330 335
Ser Gly Lys Ile Asp Glu Pro Val Leu Met Gly Ala Lys Gly Ile Ile
340 345 350
Lys Asn Lys Met Gln Ile Phe Ser Asn Gly Phe Tyr Lys Leu Pro Glu
355 360 365
Gly Lys Val Arg Phe Gly Val Leu Tyr Pro Lys Glu Phe Asp Gly Val
370 375 380
Ser Arg Lys Ala Ile Arg Ala Ile Tyr Asp Phe Ser Lys Glu Gly Lys
385 390 395 400
Tyr His Gly Glu Ser Asn Lys Tyr Ile Ala Glu His Leu Ile Asn Val
405 410 415
Glu Phe Asn Pro Lys Glu Cys Ile Phe Glu Gly Tyr Glu Leu Gly Asp
420 425 430
Ile Thr Glu Tyr Lys Lys Ala Ala Leu Lys Leu Asn Asn Tyr Asn Asn
435 440 445
Val Asp Phe Val Ile Ala Ile Val Pro Asn Met Ser Asp Glu Glu Ile
450 455 460
Glu Asn Ser Tyr Asn Pro Phe Lys Lys Ile Trp Ala Glu Leu Asn Leu
465 470 475 480
Pro Ser Gln Met Ile Ser Val Lys Thr Ala Glu Ile Phe Ala Asn Ser
485 490 495
Arg Asp Asn Thr Ala Leu Tyr Tyr Leu His Asn Ile Val Leu Gly Ile
500 505 510
Leu Gly Lys Ile Gly Gly Ile Pro Trp Val Val Lys Asp Met Lys Gly
515 520 525
Asp Val Asp Cys Phe Val Gly Leu Asp Val Gly Thr Arg Glu Lys Gly
530 535 540
Ile His Tyr Pro Ala Cys Ser Val Val Phe Asp Lys Tyr Gly Lys Leu
545 550 555 560
Ile Asn Tyr Tyr Lys Pro Asn Ile Pro Gln Asn Gly Glu Lys Ile Asn
565 570 575
Thr Glu Ile Leu Gln Glu Ile Phe Asp Lys Val Leu Ile Ser Tyr Glu
580 585 590
Glu Glu Asn Gly Ala Tyr Pro Lys Asn Ile Val Ile His Arg Asp Gly
595 600 605
Phe Ser Arg Glu Asp Leu Asp Trp Tyr Glu Asn Tyr Phe Gly Lys Lys
610 615 620
Asn Ile Lys Phe Asn Ile Ile Glu Val Lys Lys Ser Thr Pro Leu Lys
625 630 635 640
Ile Ala Ser Ile Asn Glu Gly Asn Ile Thr Asn Pro Glu Lys Gly Ser
645 650 655
Tyr Ile Leu Arg Gly Asn Lys Ala Tyr Met Val Thr Thr Asp Ile Lys
660 665 670
Glu Asn Leu Gly Ser Pro Lys Pro Leu Lys Ile Glu Lys Ser Tyr Gly
675 680 685
Asp Ile Asp Met Leu Thr Ala Leu Ser Gln Ile Tyr Ala Leu Thr Gln
690 695 700
Ile His Val Gly Ala Thr Lys Ser Leu Arg Leu Pro Ile Thr Thr Gly
705 710 715 720
Tyr Ala Asp Lys Ile Cys Lys Ala Ile Glu Phe Ile Pro Gln Gly Arg
725 730 735
Val Asp Asn Arg Leu Phe Phe Leu
740
<210> 14
<211> 735
<212> PRT
<213> artificial sequence
<400> 14
Val Ser Leu Asp Arg Glu Phe Asn Val Ile Thr Glu Phe Lys Asn Glu
1 5 10 15
Leu Lys Pro Glu Asp Ile Lys Ile Phe Leu Tyr Ser Met Pro Ile Lys
20 25 30
Asp Ile Asn Glu Arg His Ser Glu Asn Tyr Ala Ile Val Gln Glu Leu
35 40 45
Lys Lys Ile Asn Glu Asn Pro Asn Ile Val Phe Asn Glu Tyr Ile Ile
50 55 60
Ala Ser Phe Asn Pro Ile Ile Asn Trp Gly Lys Tyr Lys Asp Ile Asp
65 70 75 80
Val Lys Pro Asp Asn Arg Asn Ile Asn Leu Asp Asn Ser Thr Glu Arg
85 90 95
Lys Ile Leu Glu Arg Leu Leu Leu Cys Asp Ile Lys Asn Asn Ile Asn
100 105 110
Asn Asn Thr Thr Trp Ala Gln Gln Asn Lys Tyr Glu Ile Arg Gly Asn
115 120 125
Ala Asn Pro Ala Val Tyr Leu Arg Lys Pro Ile Tyr Leu Asn Asp Asn
130 135 140
Leu Ile Ile Arg Arg Lys Leu Asn Phe Asp Val Asn Ile Asp Lys Lys
145 150 155 160
Asp Ile Ile Ile Gly Phe Phe Leu Asn His Glu Phe Glu Tyr Gln Lys
165 170 175
Thr Leu Asp Glu Glu Ile Lys Cys Gly Asn Ile Gln Lys Gly Asp Lys
180 185 190
Val Lys Asp Phe Tyr Asn Asn Ile Thr Tyr Glu Phe Leu Glu Met Ala
195 200 205
Pro Phe Ser Ile Ser Gln Glu Asn Lys Tyr Met Arg Ser Ser Ile Ile
210 215 220
Glu Tyr Tyr Leu Asn Lys Gly Gln Ser Tyr Ile Ile Ser Gly Leu Asp
225 230 235 240
Lys Asn Thr Lys Ala Val Leu Val Lys Asn Lys Glu Gly Ser Ile Phe
245 250 255
Pro Tyr Ile Pro Asn Arg Leu Lys Lys Ile Cys Val Phe Glu Asn Leu
260 265 270
Gly Asn Arg Arg Ile Ile Glu Gly Asn Lys Tyr Ile Lys Met Asn Pro
275 280 285
Ser Gln Asn Met Ser Glu Ser Ile Lys Leu Ala Glu Asp Ile Leu Lys
290 295 300
Asn Ser Lys Tyr Val Lys Phe Asn Lys Ala Asn Met Ile Val Glu Lys
305 310 315 320
Ile Gly Tyr Lys Lys Asp Ile Val Lys Arg Pro Ala Leu Lys Phe Gly
325 330 335
Lys Asn Glu Ser Asn Phe Ser Ala Met Tyr Gly Leu Asn Lys Ser Gly
340 345 350
Ser Tyr Glu Gln Lys Asn Ile Glu Ile Asp Tyr Phe Ile Asp Pro Lys
355 360 365
Ile Leu Asn Asn Lys Arg Asp Tyr Gln Ile Val Tyr Ser Phe Leu Asn
370 375 380
Asp Ile Ile Ser Lys Ser Lys Asp Leu Gly Val Glu Ile Asn Thr Asp
385 390 395 400
Lys Ser Tyr Ile Asn Leu Thr Pro Ile Asn Ile Lys Asn Glu Asn Val
405 410 415
Phe Glu Leu Asn Ile Ile Gln Ile Ile Glu Asn Tyr Asn Asn Pro Val
420 425 430
Leu Val Ile Leu Glu Lys Glu Asn Ile Asp Lys Tyr Tyr Glu Thr Leu
435 440 445
Lys Lys Ile Phe Gly Gly Arg Asn Asn Ile Pro Thr Gln Phe Val Asp
450 455 460
Leu Asp Thr Ile Lys Lys Cys Asp Pro Lys Ile Asp Asn Lys Arg Gly
465 470 475 480
Lys Glu Ser Ile Phe Leu Asn Ile Leu Leu Gly Ile Tyr Cys Lys Ser
485 490 495
Gly Ile Gln Pro Trp Val Leu Ala Asn Gly Leu Ser Ala Asp Cys Tyr
500 505 510
Ile Gly Leu Asp Val Cys Arg Glu Asn Asn Met Ser Thr Ala Gly Leu
515 520 525
Ile Gln Val Ile Gly Lys Asp Gly Arg Val Leu Lys Ser Lys Thr Ile
530 535 540
Ser Ser His Gln Ser Gly Glu Lys Ile Gln Ile Asn Ile Leu Lys Asp
545 550 555 560
Ile Ile Phe Glu Ala Lys Gln Ala Tyr Lys Asn Thr Tyr Asn Lys Lys
565 570 575
Leu Glu His Ile Val Phe His Arg Asp Gly Ile Asn Arg Glu Asp Ile
580 585 590
Asp Leu Leu Lys Glu Ile Thr Asn Ser Leu Glu Ile Lys Phe Asp Tyr
595 600 605
Val Glu Val Thr Lys Asn Ile Asn Arg Arg Met Ala Met Leu Glu Lys
610 615 620
Ser Asp Glu Asn Tyr Asn His Arg Asp Lys Glu Asn Lys Lys Trp Ile
625 630 635 640
Thr Glu Ile Gly Met Cys Leu Lys Lys Glu Asn Glu Ala Tyr Leu Ile
645 650 655
Thr Thr Asn Pro Ser Glu Asn Met Gly Met Ala Arg Pro Leu Arg Ile
660 665 670
Lys Lys Val Tyr Gly Asn Gln Asn Met Asp Asp Ile Val Lys Asp Ile
675 680 685
Tyr Lys Leu Ser Phe Met His Ile Gly Ser Ile Met Lys Ser Arg Leu
690 695 700
Pro Ile Thr Thr Tyr Tyr Ala Asp Leu Ser Ser Ile Tyr Ser His Arg
705 710 715 720
Glu Leu Met Pro Lys Ser Val Asp Asn Asn Ile Leu His Phe Ile
725 730 735
<210> 15
<211> 780
<212> PRT
<213> artificial sequence
<400> 15
Leu Asn Ile Phe Glu Val Asp Lys Asn Arg Val Glu Val Pro Gln Asp
1 5 10 15
Val Tyr Leu Tyr Lys Val His Leu Lys Thr Leu Glu Gln Arg Lys Arg
20 25 30
Asp Met Cys Ile Ala Val Leu Arg Asn Ser Phe Gly Tyr Leu Asp Val
35 40 45
Asn Ser Phe Val Ile Tyr Ser Tyr Lys Glu Ile Arg Asp Leu Pro Arg
50 55 60
Arg Ile Lys Lys Tyr Cys Asp Leu Glu Pro Thr Gly Lys Val Lys Met
65 70 75 80
Asn Glu Val Asp Glu Asn Val Arg Asn Ala Leu Val Lys Thr Phe Leu
85 90 95
Arg Ser Lys Ile Arg Lys Asp Ile Lys Lys Leu Leu Lys Lys Phe Lys
100 105 110
Lys Phe Gln Gln Ser Val Gly Arg Trp Thr Val Ala Leu Asp Leu Glu
115 120 125
Arg Ile Glu Leu Val Glu His Asn Gly Glu Ile Leu Val Ser Phe Asn
130 135 140
Val Lys Leu Asn Ile Ser Ser Met Ile Asn Leu Trp Asp Ile Ile Glu
145 150 155 160
Arg Asp Val Asn Arg Leu Lys Gly Leu Cys Trp Ser Pro Glu Asn Leu
165 170 175
Asn Asp Asn Arg Ile Trp Phe Arg Tyr Ile Pro His Leu Ile Ile Glu
180 185 190
Glu Val Glu Asp Phe Glu Glu Ser Ala Lys Ser Phe Ile Leu Ser Asp
195 200 205
Val His Thr Gly Glu Glu Phe Gly Gly Trp Thr Thr Glu Asp Leu Lys
210 215 220
Lys Tyr Pro Glu Asn Glu Tyr Gly Leu Ser Glu Asp Ala Ile Lys Lys
225 230 235 240
Ile Gly Asn Tyr Thr Gln Phe Asp Ser Thr Gln Pro Ile Ile Lys Gly
245 250 255
Val Thr Trp Ser Gly Lys Glu Tyr Pro Phe Leu Pro Gln His Cys Ile
260 265 270
Pro Ala Tyr Asn Pro Met Leu Ala Thr Ala Glu Glu Lys Lys Arg Ile
275 280 285
Glu Glu Ile Lys Ile Asn Leu Lys Asn Lys Lys Asp Glu Ile Ile Arg
290 295 300
Lys Ile Ile Glu Gln Leu Pro Tyr Leu Lys Gln Pro Asp Asn Ile Glu
305 310 315 320
Ile Lys Lys Val Gln Glu Thr Ala Arg Leu Arg Ala Lys Phe Val Lys
325 330 335
Val Glu Val Thr Lys Gly Lys Ile Thr Lys Thr Leu Ser Gln Pro Tyr
340 345 350
Glu Lys Pro Val Ser Ser Thr Leu Asp Leu Phe Gly Trp Ile Ser Arg
355 360 365
Ile Ile Asp Gly Gly Asp Gly Ile Ile Glu Ile Cys Ile Pro Asp Tyr
370 375 380
Ile Pro Glu Asn Leu Ser Arg Ile Lys Glu Ile Glu Ala Phe Leu Leu
385 390 395 400
Ile Glu Asn Asp Leu Asn Glu Asn Glu Arg Lys Val Gly Asp Lys Leu
405 410 415
Leu Asn Asp Ala Ile Tyr Val Tyr Asn Phe Val Arg Ser Val Cys Leu
420 425 430
Arg Cys Gly Ile Asn Ile Pro Tyr Leu Asn Tyr Lys Gly Asn Arg Phe
435 440 445
Tyr Phe Glu Asn Ser Lys Glu Gly Ile Arg Asp Ile Tyr Lys Arg Ile
450 455 460
Thr Thr Ser Leu Ser Gly Glu Ile Gly Phe Ala Leu Ile Phe Gly Lys
465 470 475 480
Arg Asp Asn Tyr Glu Asp Glu Glu Gly Glu Asp Ser Phe Asp Tyr Tyr
485 490 495
Asn Pro Leu Lys Ser Ala Leu Phe Arg Asn Asn Ile Leu Ser Gln Asn
500 505 510
Phe Asp Val Thr Asn Tyr Val Arg Gly Asp Gly Lys Ile Asn Lys Asn
515 520 525
Thr Ile Lys Tyr Ala Val Ser Asn Ile Ile Tyr Asn Ile Phe Gly Lys
530 535 540
Leu Gly Val Lys Phe Phe Val Leu Glu Glu Asp Val Pro Tyr Asp Tyr
545 550 555 560
Ile Leu Gly Ile Asp Val Gly Tyr Gly Glu Ala Tyr Thr Gly Lys Val
565 570 575
Ala Gly Cys Thr Thr Val His Asp Ser Glu Gly Arg Leu Arg Asn Leu
580 585 590
Ile Pro Ile Glu Lys Gln Asn Tyr Pro Ser Lys Glu Thr Ala Arg Ile
595 600 605
Lys Ala Leu Leu Glu Glu Ile Glu Gln Lys Lys Lys Ile Tyr Asn Ile
610 615 620
Asp Phe Glu Asn Lys Ser Ile Leu Ile Leu Arg Asp Gly Arg Ile Asn
625 630 635 640
Lys Glu Glu Ile Asn Gln Leu Met Glu Phe Ser Glu Glu Arg Asn Cys
645 650 655
Arg Ile Thr Tyr Ile Glu Ile Arg Lys Asn Ile Val His Gln Phe Leu
660 665 670
Val Asn Ser Ser Gln Ala Cys Tyr Val Lys Ile Gly Asp Tyr Tyr Ile
675 680 685
Leu Lys Ala His Asn Pro Arg Ile Gly Phe Pro Arg Ala Ile Lys Ile
690 695 700
Ala Arg Lys Ile Val Ile Glu Gly Asp Ala Trp Arg Glu Ser Ser Leu
705 710 715 720
Thr Glu Asp Asp Ile Leu Leu Ile Tyr Lys Leu Thr Ala Leu Asn Tyr
725 730 735
Ser Thr Ile Gly Arg Asp Ser Asn Leu Arg Ile Pro Ala Pro Ile Tyr
740 745 750
Tyr Ala Asp Lys Leu Val Lys Ala Leu Lys Lys Gly Trp Lys Phe Asp
755 760 765
Glu Arg Phe Leu Arg Tyr Gly Ile Leu Tyr Phe Leu
770 775 780
<210> 16
<211> 758
<212> PRT
<213> artificial sequence
<400> 16
Gln Ala Glu Ile Asp Asp Ala Phe Ala Asp Val Pro Glu Ser Ala Thr
1 5 10 15
Glu Gln Thr Gly His Ala Leu Thr Thr Phe Arg Ser Glu Lys Ser Leu
20 25 30
Ser Glu Phe Ala Val His Glu Tyr Thr Leu Lys Ala Lys Asp Gly Tyr
35 40 45
Arg Pro Asp Asp His Gln Ala Ala Leu Arg Asp Thr Tyr Lys Ala Arg
50 55 60
Arg Asp Ile Leu Gly Glu Phe Glu Ser Ser Ser Pro Pro Val Ile Ala
65 70 75 80
Val Arg Asp Ala Leu Ala Leu Ala Thr Pro Ser Pro Leu Pro Val Glu
85 90 95
Asp Leu Glu Leu Lys Asn Phe Glu Met Val Asn Asp Gly Pro His Thr
100 105 110
Leu Asp Tyr Thr Asp Tyr Ser Asp Lys Ala Val Thr Lys Gly Leu Ile
115 120 125
Asp Ala Ser Leu Arg Arg Ile Leu Asp Gly Asp Tyr Glu Val Arg Gly
130 135 140
Ile Asp Thr Val Leu Ser Lys Arg Pro Val Ile Gln Lys Gln Asp Phe
145 150 155 160
Arg Leu His Glu Arg Trp Asn Leu Ser Leu Ser Val Thr Asn Ala Gly
165 170 175
Val Val Tyr Leu Ser Val Asp Phe Arg His Lys Thr Ile Ser Glu Tyr
180 185 190
Thr Leu Asp Lys Phe Asp Leu Asp Lys Leu Tyr Arg Gly Leu Arg Val
195 200 205
Asn Val Thr Tyr Lys Gln Ser Gly Lys Gly Ala Phe Val Asp Glu Leu
210 215 220
Met Asp Lys Thr Val Asn Glu Ser Ile Asp Asp Met Gly Asn Gln Ser
225 230 235 240
Val Val Glu Tyr His Glu Gly Ala Glu Arg Ile Pro Asp Arg Val Leu
245 250 255
Lys Glu Ile Ala Arg Ala Asp Arg Arg Val Val Lys Val Thr Lys Gln
260 265 270
Gly Ser His Asn Thr Glu Tyr Tyr Pro Gln Arg Leu Leu Ala Leu Gln
275 280 285
Gly His Pro Gln Asn Val Lys Ala Phe Ala Pro Arg Phe Asn Glu Ala
290 295 300
Thr Arg Gly Lys Thr Arg Leu Ser Ala Gln Arg Cys Leu Asn Arg Ala
305 310 315 320
Thr Thr Phe Val Glu Asn Leu Pro Pro Val Ile Pro Leu Gly Gly Ala
325 330 335
Thr Leu Ser Phe Asp Ala Thr Pro Val Asn Gly Asp Asp Thr Trp Glu
340 345 350
Met Ser Arg Leu Phe Glu Thr Asp Ala His Ile Leu Gln Phe Ala Glu
355 360 365
Glu Gln Thr Gly Asp His Pro Arg Arg Val Lys His Asn Glu Val Tyr
370 375 380
Glu Ala Pro Glu Glu Phe Ser Val Cys Leu Val His Pro Ser Ala Gly
385 390 395 400
Pro His Ala Glu Arg Trp Glu Asn Leu Asp Gln Gln Leu Lys Asp Ile
405 410 415
Gly Ala Gly Pro Glu Ala Val Asn Arg Val Gln Tyr Asp Pro Phe Lys
420 425 430
Thr Ala Asp Glu Ile Tyr Thr Asp Leu Leu Val Asp Val Pro Asp Asp
435 440 445
His Glu Tyr Ser Ala Ala Cys Val Ile Leu Pro Lys Ala Asp Phe Ser
450 455 460
Met Gly Glu Ser Ser Ala Ser Asp Ile Tyr His Glu Met Lys Lys Ala
465 470 475 480
Leu Arg Gln Arg Arg Val Asp Ser Gln Met Ala His Ile Asp Thr Leu
485 490 495
Ala Thr Ser Tyr Ala Leu Pro Asn Val Ala Leu Gly Leu Val Ala Ala
500 505 510
Ala Gly Gly Ile Pro Phe Thr Thr Glu Asp Ala Met Pro Gly Glu Thr
515 520 525
Asp Leu Phe Ile Gly Ile Asp Val Ser His Arg Tyr Pro Arg Asp Thr
530 535 540
Asp Glu Arg Val His Ile Ala Ala Ser Thr Thr Ser Ile Tyr Gly Asp
545 550 555 560
Gly Thr Ile Leu Gly Tyr Thr Ser Ala Lys Pro Gln Thr Gly Glu Lys
565 570 575
Val Pro Pro Lys Glu Leu Lys Asn Leu Thr Arg Gln Ser Ile Ala Gly
580 585 590
Tyr Lys Gln Glu His Gly Glu Tyr Pro Asp Arg Ile Val Ile His Arg
595 600 605
Asp Gly Phe Met Arg Glu Asp Leu Asp Gln Val Glu Glu Met Leu Glu
610 615 620
Ser Met Asp Ile Asn Tyr Asp Val Val Glu Ile Arg Lys Gln Ser Pro
625 630 635 640
Ala Arg Val Leu Asn Leu Ala Asp Gly Val Ala Lys Ile Pro Asp Lys
645 650 655
Gly Ile Ala Ala Leu Asn Arg Glu Glu Asn Arg Ala Ile Leu Ala Thr
660 665 670
Phe Gly Asp Pro Glu Ser Gln Ala Thr Ser Ser Asn Thr Gly Leu Pro
675 680 685
Gln Pro Ile Gln Val Glu Arg Lys Ala Gly Asp Thr Asp Ile Lys Thr
690 695 700
Leu Thr Ala Gln Val Tyr Leu Leu Ser Gln Ser His Val Gly Ala Met
705 710 715 720
Asn Ser Thr Ala Arg Leu Pro Ile Thr Thr Tyr Tyr Ala Asp Arg Ala
725 730 735
Ser Glu Ala Ala Ala Glu Gly Tyr Leu Pro Glu Thr Ser Lys Leu Arg
740 745 750
Gln Asn Ile Gly Phe Ile
755
<210> 17
<211> 705
<212> PRT
<213> artificial sequence
<400> 17
Lys Asn Leu Arg Tyr Lys Ile Asn Ala Tyr Arg Ile Lys Lys Asp Tyr
1 5 10 15
Ile Pro Lys Glu Val Tyr Arg Tyr Arg Ile Arg Ser Phe Ile Glu Asn
20 25 30
Ile Asn Ile Tyr Arg Phe Val Gly Phe Tyr Gly Gly Val Ala Leu Asn
35 40 45
Gln Ser Glu Phe Ile Leu Pro Tyr Pro Val Glu Asn Leu Val Leu Glu
50 55 60
Tyr Asp Gly Lys Asp Val Lys Leu Glu His Ile Asp Thr Leu Asn Leu
65 70 75 80
Glu Asp Ile Glu Asn Lys Asp Lys Glu Lys Ala Glu Lys Leu Val Arg
85 90 95
Gly Tyr Leu Thr Ser Ile Tyr Lys Leu Lys Pro Ile Leu Tyr Lys Ile
100 105 110
Leu Arg Asp Val Arg Glu Ser Lys Ile Ile Asn Asp Ile Arg Val Asp
115 120 125
Pro Ile Pro Asp Phe Thr Val Lys Arg His Asn Asn Glu Tyr Tyr Leu
130 135 140
Val Ile Asp Phe Asn His Thr Ala Thr Val Leu Lys Asn Leu Trp Asp
145 150 155 160
Phe Val Gly Arg Asp Lys Leu Lys Leu Glu Asp Tyr Ile Gly Lys Lys
165 170 175
Ile Ile Phe Lys Pro Asn Pro Lys Lys Arg Tyr Thr Ile Lys Ser Ile
180 185 190
Glu Lys Gln Asn Lys Lys Asp Ile Asp Asp Ile Val Glu His Ile Ile
195 200 205
Glu Tyr Tyr Lys Trp Thr Glu Glu Glu Ile Lys Ser Thr Phe Gly Glu
210 215 220
Ile Asp Tyr Thr Gln Pro Ile Ile His Cys Glu Gly Ile Pro Tyr Pro
225 230 235 240
Phe Ala Pro Gln Phe Cys Asn Ile Val Phe Thr Met Glu Asp Leu Asp
245 250 255
Glu Asn Thr Leu Lys Asp Leu Gln Ser Tyr Trp Arg Leu Pro Asn Glu
260 265 270
Ile Lys Gly Asn Ile Ile Asn Gln Ile Ala Lys Lys Leu Arg Phe Val
275 280 285
Glu Asn Glu Pro Ile Glu Leu Glu Phe Ile Lys Phe Asn Asn Thr Pro
290 295 300
Leu Ile Val Lys Asp Glu Asn Gly Lys Pro Thr Lys Ile Tyr Thr Thr
305 310 315 320
Asn Arg Leu Phe Arg Trp Asn Tyr Asp Ser Lys Ser Lys Leu Tyr Leu
325 330 335
Pro Tyr Asp Ile Pro Asp Ile Ile Lys Asn Lys Thr Leu Thr Thr Phe
340 345 350
Val Leu Ile Asp Glu Asn Leu Lys Asn Val Ser Gly Lys Ile Lys Arg
355 360 365
Lys Val Tyr Gln Met Phe Lys Asn Tyr Asn Lys Ile Ala Ser Lys Thr
370 375 380
Glu Leu Pro Lys Phe Asp Phe Ala Asn Lys Trp Lys Tyr Phe Ser Asn
385 390 395 400
Asn Asn Ile Arg Asp Val Ile Arg Lys Ile Lys Asp Glu Phe Asn Glu
405 410 415
Glu Leu Gly Phe Ala Leu Ile Ile Gly Asn Arg Tyr Tyr Glu Asn Asp
420 425 430
Tyr Tyr Glu Thr Leu Lys Met Gln Leu Phe Asn Leu Asn Ile Ile Ser
435 440 445
Gln Asn Ile Leu Trp Glu Asn Trp Ser Lys Asp Asp Asn Asn Phe Met
450 455 460
Thr Asn Asn Leu Leu Ile Gln Ile Met Gly Lys Leu Gly Ile Lys Tyr
465 470 475 480
Phe Ala Leu Asp Ala Lys Val Asn Tyr Asp Tyr Ile Met Gly Leu Asp
485 490 495
Ser Gly Leu Gly Ala Phe Lys Ser Asn Arg Val Ser Gly Cys Thr Val
500 505 510
Ile Tyr Asp Ser Glu Gly Lys Ile Arg Arg Ile Gln Pro Ile Asp Val
515 520 525
Pro Ser Pro Gly Glu Arg Ile Pro Ile His Leu Val Val Glu Phe Leu
530 535 540
Glu Thr Lys Thr Asp Ile Asn Met Glu Asn Lys Asn Ile Leu Phe Leu
545 550 555 560
Arg Asp Gly Phe Val Gln Asn Ser Glu Arg Glu Glu Leu Lys Lys Leu
565 570 575
Ser Lys Glu Leu Asn Ser Asn Ile Glu Val Ile Ser Ile Arg Lys Asn
580 585 590
Asn Lys Tyr Lys Val Phe Thr Ser Asp Tyr Gly Ile Gly Ser Ile Phe
595 600 605
Gly Asn Asp Gly Ile Phe Leu Pro His Lys Thr Thr Phe Gly Ser Asn
610 615 620
Pro Val Lys Leu Ser Thr Trp Leu Arg Phe Asn Ser Gly Asn Glu Glu
625 630 635 640
Lys Leu Lys Ile Asn Glu Ser Ile Met Gln Leu Leu Tyr Asp Leu Thr
645 650 655
Lys Met Asn Tyr Ser Ala Leu Tyr Gly Glu Gly Arg Asn Leu Arg Ile
660 665 670
Pro Ala Pro Ile His Tyr Ala Asp Lys Phe Val Lys Ala Leu Gly Lys
675 680 685
Asn Trp Lys Ile Asp Glu Glu Leu Leu Lys His Gly Phe Leu Tyr Phe
690 695 700
Ile
705
<210> 18
<211> 742
<212> PRT
<213> artificial sequence
<400> 18
Ser Lys Val Gly Ile Ala Ala Leu Gln Leu Glu Arg Asn Leu Gly Ser
1 5 10 15
Leu Pro Val Tyr Val Tyr Asp Leu Thr Phe Val Ser Ser Pro Ser Asp
20 25 30
Gln Glu Pro Ile Gln Leu Thr Arg Arg Gly Ala Ser Gln Leu Ser Trp
35 40 45
Val Asn Arg Gln Thr Ala Ile Thr Asp Phe Gly His Phe Lys Leu Val
50 55 60
Thr Leu Arg Pro Leu Ser Ala Tyr Glu Ala Asn Trp Gln Gly Val His
65 70 75 80
Cys Val Val Gln Gly Glu Arg Glu Leu Thr Leu Ser Ala Glu Asn Glu
85 90 95
Leu His Arg Glu Thr Ile Lys Arg Leu Val Asn Gln Cys Leu Met Gln
100 105 110
Gly Thr Arg Gln Leu Ala Asn Val Ser Asn Gly Ala Met Gln Ala Glu
115 120 125
Tyr Gly Gln Gly Tyr Gln Val Glu Leu Ile Asp Cys Leu Ala Ser Ser
130 135 140
Arg Val Ala Val Arg Asn Glu Phe Leu Asp Val Phe Gln Cys Leu Arg
145 150 155 160
Leu Val Pro Glu Val Leu Pro Asp Gly Ser Thr Leu Val Ser Phe Met
165 170 175
Val Arg His Arg Leu Leu Pro Arg Glu His Ile Thr Leu Asp Trp Val
180 185 190
Ile Lys Thr Arg Pro Glu Trp Leu Glu Ser Ile Lys Arg Val Arg His
195 200 205
Arg Tyr Ser Ser Gln Gly Lys Ala Pro Gly Ser Ala Asn Phe Ile Ala
210 215 220
Val Glu Lys Ser Arg Ser Ala Gln Ser Gln Ile Ser Thr Ala Gln Gly
225 230 235 240
Lys Ile Ser Leu Phe Asp Tyr His Asp Gln Arg Gly Asn Ile Leu Pro
245 250 255
Gly Glu Lys Ser Leu Ala Tyr Asp Ser Ser Val Val Lys Val Ser Tyr
260 265 270
Gly Arg Ser Lys Glu Ser Phe Glu His Leu Ala Thr Leu Leu Gln Pro
275 280 285
Met Phe Asp Phe Glu Ala Leu Gln Gly Ile Asp Ser Lys Leu Leu Glu
290 295 300
Arg Ile Ala Lys Gly Leu Lys Trp Pro Ile Ala Asp Arg Leu Glu Ala
305 310 315 320
Ala Ala Gln Arg Ile Lys Asn Leu Lys Val Gly Glu Leu Ala Cys Gly
325 330 335
Leu Thr Thr Val Arg Asn Leu Asp Glu Arg Val Gln Tyr Leu Arg Pro
340 345 350
Pro Ile Arg Leu Arg Phe Ala Asn Asp Lys Ile Gly Asp His Glu Lys
355 360 365
Leu Val Thr Lys His Gly Ala Phe Arg Gly Met Gln Arg Glu Leu Val
370 375 380
Val Pro Ile Val Ile Gly Gly Thr Asn Glu Glu Gln Gln Ala Ala Lys
385 390 395 400
Gln His Phe Tyr Asn Val Glu Lys Ile Cys Gln Leu Trp Ser Asn Glu
405 410 415
Ser Pro Arg Trp Lys Gln Val Pro Ser Ala Asn Asp Glu Leu Glu Leu
420 425 430
Asp Ala Arg Leu Ser Ser Lys Thr Leu Pro Glu Ala Leu Leu Phe Ile
435 440 445
Ala Leu Gly Arg Asn Ala Asn Lys Gln Ala Ile Arg Asn Val Ala Tyr
450 455 460
Arg Tyr Gly Leu Ala Thr Gln Phe Met Arg Leu Asp His Pro Ala Arg
465 470 475 480
Ile Tyr Gln Gln Thr Tyr Tyr Asn Asn Leu Ala Ala Gly Leu Phe Ser
485 490 495
Lys Ala Gly Gly Leu Ile Cys Gly Leu Asp Gln Met Pro Gly Asp Thr
500 505 510
Asp Leu Phe Ile Gly Leu Asp Leu Gly Gly Val Gly Gln Arg Leu Pro
515 520 525
Gly Thr Ala Phe Leu Phe Thr Arg Ser Gly Ala Gln Leu Gly Trp Gln
530 535 540
Leu Ala Glu Ala Gln Lys Gly Glu Arg Val Glu Asn Glu Val Leu His
545 550 555 560
Asp Leu Leu Glu Arg Ser Leu Gln Ala Phe Val Arg Ala Asn Asp Gly
565 570 575
Leu Leu Pro Gln Arg Ile Thr Leu His Arg Asp Gly His Leu Tyr Glu
580 585 590
Ser Leu Asp Val Ile Lys Arg Phe Glu Gln Lys His Asn Val Gly Ile
595 600 605
Asp Val Leu Glu Val Ile Lys Ser Gly Cys Pro Pro Leu Phe Arg Arg
610 615 620
Ser Gln Gly Pro Glu Gly Lys Ala Ile Tyr Ser Asn Pro Glu Val Gly
625 630 635 640
Asp Ala Phe Glu Leu Ser Gly Leu Asp Glu Leu Ile Val Ala Thr Tyr
645 650 655
Ser Ser Gln Asp Leu Gly Gln Ala Trp Gly Asp Lys Val Thr Val Arg
660 665 670
Pro Leu Arg Leu Arg Lys Arg Tyr Gly Leu Thr Asp Leu His Thr Leu
675 680 685
Ala Lys Gln Val Ile Leu Leu Ser Arg Ile His Gly Ala Ser Leu Tyr
690 695 700
Arg His Pro Arg Leu Pro Val Thr Thr His His Ala Asp Arg Phe Ala
705 710 715 720
Ser Leu Arg Gln Glu Cys His Leu Asp Asp Leu Ser Arg Met Asp Arg
725 730 735
Leu Cys Pro Val Tyr Leu
740
<210> 19
<211> 798
<212> PRT
<213> artificial sequence
<400> 19
Phe Arg Val Asp Leu Glu Thr Ile Arg Gly Glu Leu Glu Gly Ser Pro
1 5 10 15
Ser Ile Asn Val Tyr Gly Leu Ala Phe Lys Glu Pro Ile Arg Glu Asp
20 25 30
Asp Pro Cys Ile Gln Ala Leu Glu Asn Ile Gly Tyr Tyr Asp Gly Gly
35 40 45
Ser Arg Arg Leu Tyr Thr Thr Arg Pro Ile Gly Asp Leu Pro Glu Pro
50 55 60
Cys Arg Asp Ser Val Ser Leu Gly Ser His Lys Ala Val Thr Leu Lys
65 70 75 80
Glu Val Pro Val Asp Gly Ile Arg Ser Ile Ile Lys Val Tyr Val Arg
85 90 95
Asp Lys Val Leu Arg Gly Ser Arg Ala Val Leu Glu Glu Ser Asp Glu
100 105 110
Val Gly Gly Ile Leu Asp Glu Val Leu Lys Gly Leu Thr Ser Lys Gly
115 120 125
Tyr Arg Asn Val Arg Arg Ser Arg Ser Val Phe His Val Gly Arg Trp
130 135 140
Asn Ala Arg Leu Thr Val Asp Ser Asn Asp Val Tyr Val Phe Trp Phe
145 150 155 160
Asn Asp Glu Leu Phe Val Ala Leu Asn Val Gly Leu Asp Ile Asp Tyr
165 170 175
Asn Gly Asn Leu Trp Asp His Met Ala Glu Arg Ser Leu Asp Lys Leu
180 185 190
Arg Ser Leu Val Glu His Val Arg Cys Arg Tyr Ile Leu Asp Ile Ala
195 200 205
Arg Gly Arg Pro Gly Thr Tyr Val Val Ala Asn Val Ile Asp Arg Ser
210 215 220
Ser Tyr Glu Glu Lys Ser Pro Pro Met Gly Tyr Glu Glu Leu Val Lys
225 230 235 240
Tyr Pro Val Val Lys Ala Arg Glu Glu Gly Leu Glu Thr Arg Phe Glu
245 250 255
Arg Leu Met Lys Lys Leu Val Gly Glu Val Asp Pro Asn Gln Pro Val
260 265 270
Leu Glu Ala Thr Arg Ala Gly Lys Met Gly Arg Arg Pro Val Tyr Ile
275 280 285
Pro Ala Gln Tyr Cys Ile Pro Val Tyr Asp Pro Arg Leu Ala Glu Lys
290 295 300
His Glu Asp Arg Ala Leu Ala Lys Leu Arg Glu Leu Val Asn Ser Ile
305 310 315 320
Gly Tyr Lys Gly Lys Leu Ile Asn Ala Ile Ala Arg Ser Leu Gly Tyr
325 330 335
Leu Ser Glu Ala Thr His Leu Asn Ile Glu Arg Ile Glu Gly Glu Lys
340 345 350
Pro Leu Lys Val Glu Leu Val Glu Val Glu Tyr Asn Gly Gly Lys Pro
355 360 365
Ser Ile Ile Asn Arg Ser Lys Arg Glu Val Ser Phe Thr Ala Asp Val
370 375 380
Met Lys Pro Leu Arg Leu Ile Ser Ile Val Lys Glu Val Glu Glu Gly
385 390 395 400
Arg Arg Val Lys Ile Glu Ile Pro Val Pro Asn Tyr Val Pro Ala Thr
405 410 415
Leu Arg Glu Leu Asp Glu Leu Gln Leu Leu Val Leu Val Glu Asp Gly
420 425 430
Leu Asp Pro Leu Ser Phe Glu Ile Met Asp Val Val Val Glu Asn Val
435 440 445
Thr Arg Leu Tyr Glu Ile Val Arg Glu Val Tyr Glu Pro Leu Lys Ile
450 455 460
Lys Leu Pro Lys Leu Arg Val His Arg Gln Pro Ile Leu Phe Thr His
465 470 475 480
Gly Asp Tyr Ser Asn Val Leu Lys Glu Val Arg Lys Val Thr Gly Gly
485 490 495
Lys Leu Ala Phe Ala Phe Ile Leu Gly Glu Arg Pro Ala Asp Asp Glu
500 505 510
Glu Asp Tyr Tyr Arg Pro Leu Lys Lys Val Leu Phe Lys Gly Asn Val
515 520 525
Ile Ser Gln Asn Ile Asp Val Arg Lys Tyr Val Ser Asp Gly Arg Val
530 535 540
Asp Lys Arg Ile Leu Met Pro Ala Ile Ser Asn Met Phe Tyr Asp Met
545 550 555 560
Leu Gly Lys Leu Gly Val Lys Tyr Leu Thr Leu Ser Lys Ser Thr Asp
565 570 575
Tyr Asp Leu Ile Ile Gly Val Asp Val Gly His Gly Glu Val Glu Gly
580 585 590
Ser Arg Ile Val Gly Ser Val Val Leu Phe Asp Lys Met Gly Arg Leu
595 600 605
Met Asn Leu Val Pro Val Tyr Gly Leu Gly Tyr Pro Gly Arg Glu Thr
610 615 620
Ala Arg Ile Gly Asp Leu Leu Glu Gln Ile Glu Tyr Glu Asn Tyr Ala
625 630 635 640
Glu Leu Lys Gly Lys Arg Ile Leu Val Leu Arg Asp Gly Arg Leu Thr
645 650 655
Lys Glu Glu Val Thr Gln Leu Ala Asp Ile Ser Arg Thr Lys Asp Cys
660 665 670
Thr Ile Glu Val Ile Asn Val Lys Lys Arg Thr Pro Phe Gln Gln Leu
675 680 685
Ser Asp Ser Arg Val Ala Trp Phe Val Asp Ile Gly Asp Ala Tyr Leu
690 695 700
Leu Lys Thr His Met Leu Lys Arg Asp Met Leu Pro Arg Pro Ile Lys
705 710 715 720
Ile Asp Lys Val Lys Tyr Val Phe Ala Lys Gly Thr Val Arg Glu Glu
725 730 735
Arg Val Ser Val Asp Asp Leu Arg Leu Leu Arg Gly Leu Ser His Leu
740 745 750
Asn Tyr Ser Thr Ile Glu Gly Glu Thr Gly Leu Arg Leu Pro Ala Pro
755 760 765
Val His Tyr Ala Asp Lys Leu Leu Asp Ala Leu Arg Ser Gly Trp Glu
770 775 780
Ile Glu Arg Arg Tyr Leu Arg Asp Gly Leu Leu Tyr Phe Leu
785 790 795
<210> 20
<211> 726
<212> PRT
<213> artificial sequence
<400> 20
Pro Val Tyr Tyr Tyr Arg Leu Thr Phe Asp Asp Asp His Glu Asp Ile
1 5 10 15
Asn Pro Thr Gln Leu Thr Arg Arg Gly Ala Arg Met Leu Ser Gly Ala
20 25 30
Asn Gly Trp Cys Ala Val Thr Asp Gly Glu Pro Leu Arg Val Leu Ser
35 40 45
Leu Arg Pro Leu Lys Val Leu Arg His Glu Trp Asn Gly Met Cys Cys
50 55 60
Thr Ala Ser Asp Glu Thr Ala Gly Thr Leu Lys Ser Ala Asn Pro Ser
65 70 75 80
Glu Arg Glu Ala Ile Gln Arg Leu Leu Asn Gln Cys Leu Met Gln Gly
85 90 95
Ala Arg Lys Leu Ala Tyr Ser Ser Asp Gly Gly Leu Glu Ala Glu Gln
100 105 110
Gly Ala Gly Asn Leu Val Arg Leu Thr Ala Cys Gln Pro Ser Glu Arg
115 120 125
Val Ser Ala Gly Gly Asp Tyr Leu Asp Ala Phe Gln Ser Val Thr Leu
130 135 140
Ile Pro Asp Val Leu Pro Asp Gly Thr Ala Leu Val Gly Phe Asp Val
145 150 155 160
Arg His Arg Leu Leu Pro Arg Pro His Leu Thr Leu Asp Trp Val Ile
165 170 175
Arg Lys Arg Pro Glu Trp Met Glu Gly Ile Arg Arg Val Arg His Arg
180 185 190
Tyr Val Ser Asn Gly Gln Tyr Gly Thr Ala Glu Leu Ile Gly Ile Ala
195 200 205
Thr Gly Arg Thr Ala Leu Ser Thr Phe Pro Thr Pro Lys Gly Glu Val
210 215 220
Ser Leu Leu Gly Tyr His Glu Ser Lys Gly Asn Leu Pro Glu Gly Glu
225 230 235 240
Arg Glu Ala Val Ala Ala Ser His Val Val Gln Val Arg Tyr Gly Arg
245 250 255
Asp Thr Arg Ala Lys Pro Met Glu His Leu Ala Ala Leu Leu Gln Pro
260 265 270
Met Phe Gly Phe Asp Thr Leu Ser Gln Ile Asp Ser Arg Leu Leu Glu
275 280 285
Arg Ile Ala Arg Ser Leu Lys Trp Pro Val Gly Glu Arg Leu Lys Ala
290 295 300
Ala Ile Arg Leu Val Lys Gly Leu Lys Val Ser Glu Leu Asp Ala Cys
305 310 315 320
Leu Gln Ala Val Glu Asp Thr Gln Arg Phe Ala Arg Asp Leu Lys Pro
325 330 335
Glu Phe Arg Leu Leu Phe Arg Gly Ala Ala Val Ala Asp Ser Glu Arg
340 345 350
Ala Val Leu Arg His Gly Ala Tyr Gln Gly Met Thr Arg Lys Leu Val
355 360 365
Val Pro Leu Val Val Gly Gly Thr Ala Leu Glu Gln Ala Val Ala Val
370 375 380
Arg His Phe Glu Ala Val Glu Arg Val Cys Arg Gln Trp His Ser Asp
385 390 395 400
Leu Pro Ser Trp Lys Thr Ala Pro Pro Ala Gly Asp Ala Glu Ala Leu
405 410 415
Asn Gln Arg Leu Ala Gln Arg Lys Pro Glu Asn Ala Leu Leu Leu Ile
420 425 430
Gly Leu Gly Arg Gly Ala Asp Lys Arg Lys Ile Arg Asn Val Ala Tyr
435 440 445
Arg Tyr Gly Leu Ala Thr Gln Phe Met Arg Leu Asp His Pro Pro Arg
450 455 460
Thr Tyr Gln Ser Thr Tyr Tyr Asn Asn Leu Ala Ala Gly Val Phe Ser
465 470 475 480
Lys Gly Gly Gly Val Leu Cys Ala Ile Asp Asp Met Pro Gly Glu Thr
485 490 495
Asp Leu Phe Ile Gly Leu Asp Leu Gly Gly Val Ser Gln Arg Ala Pro
500 505 510
Gly Leu Ala Phe Leu Phe Thr Arg Glu Gly Ala Gln Leu Gly Trp Gln
515 520 525
Leu Ala Glu Ala Gln Arg Gly Glu Arg Val Glu Asp Ala Val Leu Gly
530 535 540
Asp Leu Leu Glu Arg Ser Leu Gln Ala Tyr Arg Gln Val His Leu Gly
545 550 555 560
Ala Leu Pro Arg Arg Ile Ala Leu His Arg Asp Gly Arg Leu Phe Glu
565 570 575
Ser Leu Asp Val Ile Arg Asn Phe Glu Arg Asp Tyr Ser Val Arg Val
580 585 590
Asp Val Leu Glu Val Val Lys Ser Gly Cys Pro Pro Leu Tyr Arg Arg
595 600 605
Gly Val Val Ala Glu Asn Lys Lys Ala Phe Arg Asn Pro Glu Val Gly
610 615 620
Asp Ala Phe Glu Leu Pro Gly Leu Asp Glu Leu Ile Ile Ala Thr Tyr
625 630 635 640
Ser Gly Glu Glu Leu Gly Ser Ser Trp Gly Asp Lys Val Thr Val Arg
645 650 655
Pro Leu Arg Leu Arg Lys Arg Tyr Gly Glu Thr Asp Leu His Thr Leu
660 665 670
Ala Arg Gln Val Val Leu Leu Ser Arg Ile His Gly Ala Ser Leu Tyr
675 680 685
Arg His Pro Arg Leu Pro Val Thr Thr His His Ala Asp Arg Phe Ala
690 695 700
Thr Leu Arg Gln Glu Cys Asn Leu Asp Asp Leu Ser Lys Met Asp Arg
705 710 715 720
Leu Cys Pro Val Tyr Leu
725
<210> 21
<211> 614
<212> PRT
<213> artificial sequence
<400> 21
Ile Cys Trp Gln Lys Thr Glu Ala Asp Ile Arg Ser Asp Val Ser Gly
1 5 10 15
Trp Glu Ile Tyr Arg Gly Phe Lys Leu Asp Ile Phe Val Ser Ser Gln
20 25 30
Gly Asn Val Phe Leu Glu Val Asp Glu His Tyr Lys Leu Phe Ser Ala
35 40 45
Trp Thr Leu Thr Gln Trp Leu Glu Trp Tyr Pro Asp Phe Ser Ala Lys
50 55 60
Ile Leu Arg Asn Thr Tyr Asp Gly Arg Thr Trp Lys Leu Gln Lys Ile
65 70 75 80
Thr Asn Glu Asp Pro Asn Asn Ile Asp Ser Gly Thr Gly Gln Thr Leu
85 90 95
Ala Thr Tyr His Lys Asn His Gln Lys Pro Ala Thr Asp Gln Glu Ile
100 105 110
Asn Ser Ser Lys Val Ile Tyr Val Lys Pro Tyr Asn Ser Lys Lys Glu
115 120 125
Glu Ser Tyr Pro His Leu Ser Ser Arg Val Lys Pro Cys Leu Phe Leu
130 135 140
Asp Thr Leu Ser Glu Leu Ala Ser Gln Gly Asp Arg Lys Val Lys Glu
145 150 155 160
Val Phe Asn Leu Ile Lys Pro Ser Ile Glu Asp Arg Phe Ser Arg Ala
165 170 175
Thr Glu Ile Ala Lys Gln Leu Ala Val Glu Ile Tyr Asn Ile Asp Glu
180 185 190
Glu Ile Ser Asp Asp Ile Lys Val Val Gln Val Gln Ala Gln Gln Ser
195 200 205
Ser Gln Asp Lys Ser Ile Leu Leu Ala His Ser Ser Lys Arg Ile Asp
210 215 220
Lys Val Phe Lys Ser Leu Asp Gln Gly Cys Phe Arg Val Gly Glu Ile
225 230 235 240
Lys Phe Gly Cys Ile Asn Leu Leu Asp Lys Asn Gln Asp Gly Trp Ser
245 250 255
Lys Phe Ile Leu Gln Lys Leu Gln Lys Leu Ala Thr Ile His Asn Ile
260 265 270
Asn Ile Asp Ala Asn Leu Val Lys Ala Ala Val Asp Ile Pro Glu Lys
275 280 285
Asp Phe Glu Ile Asp Gln Phe Trp Glu Ser Trp Val Glu Gln Asp Ile
290 295 300
Lys Thr Ile Leu Val Ile Ser Glu Trp Leu Asp Asn Lys Tyr Lys Thr
305 310 315 320
Lys Leu Thr Arg Asp Ala Leu Glu His Gly Ile Thr Leu Gln Phe Met
325 330 335
Leu Pro Leu Lys Glu Asn Val Arg Arg Ile Glu Ser Asn Lys Gly Val
340 345 350
Glu Ser Lys Ile Thr Cys Phe Thr Ser Asp Gln Tyr Arg Ala Asn Asn
355 360 365
Ile Leu Leu Gly Leu Leu Ala Lys Ala Gly Trp Gln Ala Val Gly Leu
370 375 380
Pro Leu Leu Asn Asn Glu Tyr Ala Ala Asp Leu Val Ile Gly Phe Asp
385 390 395 400
Ala Gly Arg Asn Glu Thr Leu Ser Tyr Gly Thr Ser Ser Phe Ala Val
405 410 415
Leu Ala Asp Gly Gln Ile Leu Gly Trp Glu Leu Pro Glu Ala Gln Lys
420 425 430
Gly Glu Ile Leu Asp Pro Asp His Val Arg Arg Thr Val Arg Arg Ile
435 440 445
Ile Ser Gln Phe Gln Lys Met Asn Gly Lys Gln Ser Pro Lys Arg Ile
450 455 460
Leu Leu Met Arg Asp Gly Leu Ile Gln Gln Gln Glu Phe Ser Leu Ile
465 470 475 480
Thr Glu Ala Leu Glu Glu Gly Glu Ile Lys Tyr Asp Leu Ile Ser Val
485 490 495
Arg Lys Ser Gly Ala Gly Arg Ile Gly Arg Arg Asn Ser Asp Gly Thr
500 505 510
Tyr Val Asp Ala Pro Lys Gly Thr Val Ile Phe Ser Gly Asn Asp Lys
515 520 525
Phe Lys Ile Val Thr Ser Glu Ala Lys Ala Gly Gly Ser Ala Arg Pro
530 535 540
Leu Phe Val Val Arg Glu Gln Gly Asp Thr Pro Ile Glu Ile Ile Ala
545 550 555 560
Glu Gln Phe Tyr Arg Leu Thr Gln Leu His Pro Val Ser Gly Ser Phe
565 570 575
Thr Ser Arg Leu Pro Met Pro Leu Asn Tyr Ala Asp Lys Leu Ala Lys
580 585 590
Lys Ile Gln Ser Leu Gly Ser Val Gly Ile Leu Gln Asn Leu Asp Arg
595 600 605
Lys Lys Leu Phe Phe Val
610
<210> 22
<211> 765
<212> PRT
<213> artificial sequence
<400> 22
Glu Lys Gln Thr Phe Tyr Gln Gly Asn Met Tyr Arg Leu Lys Asp Glu
1 5 10 15
Leu Ile Gln Asp Ile Leu Ser Asp Ile Ile Val Ala Arg Val Thr Asn
20 25 30
Met Pro Ser Asn Pro Glu Glu Ala Tyr Ser Glu Ile Gln Lys Ile Gly
35 40 45
Gly Ile Ile Leu Asn Tyr Asp Glu Met Thr Asn Ser Ala Trp Val Val
50 55 60
Gly Lys Glu Ser Leu Leu Gln Asn His Tyr Pro Asp Asp Met Lys Glu
65 70 75 80
Val Arg Ala Phe Ser Phe Ser Glu Leu Ser Lys Glu Asn Lys Thr Lys
85 90 95
Leu Val Leu Asn Ile Leu Asn Ala Glu Gly Tyr Leu Arg Asp Ile Arg
100 105 110
Gly His Arg Glu Val Val Lys Ser Ile Asn Ser Glu Arg Ser Ile Ile
115 120 125
Arg Lys Phe Leu Val Thr Val Glu Tyr Asp Gly Gln His Phe Tyr Leu
130 135 140
Val Thr Leu Pro Lys Tyr Lys Ile Ile Glu Asn His Thr Ile Met Glu
145 150 155 160
Leu Leu Ile Glu Gly Lys Ile Thr Val Lys Glu Leu Val His Asn Leu
165 170 175
Leu Lys Asp Pro Lys Trp Lys Ile Gln Thr Ser Arg Lys Asp Val Pro
180 185 190
Leu Pro Pro Gly His Arg Val Val Glu Ile Ile Leu Lys Thr Lys Asp
195 200 205
Pro Asp Arg Tyr Gln Gln Glu Leu Glu Arg Ile Asn Glu Tyr Phe Thr
210 215 220
Lys Lys Thr Glu Leu Gly Pro Ile Asp Asp Ser Lys Tyr Pro Asp Asp
225 230 235 240
Tyr Asn Ile Ile Phe Arg Ser Gln Thr Arg Gly Lys Tyr Leu Ser Tyr
245 250 255
His Ser Ala Arg Thr Lys Leu Ile Arg Pro Ile Asn Lys Glu Ile Leu
260 265 270
Arg Glu Ile Tyr Arg Ser Asn Glu Phe Ile Lys Ala Leu Asn Ile Ala
275 280 285
Lys Lys Leu Val Ala Asp Ile Ile Tyr Asp Ser Thr Lys Tyr Pro Gly
290 295 300
Arg Ala Ile Phe Pro Ala Phe Lys Ile Asp Glu Arg Thr Ile Ser Tyr
305 310 315 320
Lys Ala Val Phe Leu Lys Asn Lys Thr Ile Thr Glu Lys Thr Ile Gln
325 330 335
Pro Tyr Tyr Asn Ile Lys Gly Thr Phe Asn Trp Leu Phe Thr Asn Thr
340 345 350
Pro Phe Asp Asp Ile Ser Glu Leu Ile Ile Pro Ile Gln Ser Pro Glu
355 360 365
Phe Leu Arg Asp Lys Thr Ile Gly Val Tyr Ile Leu Tyr Pro Ala Lys
370 375 380
Tyr Arg Glu Asn Ser Glu Ser Leu Lys Val Ile Gln Asn Leu Ile Lys
385 390 395 400
Ser Val Asp Ser Thr Ile Lys Arg Leu Ser Glu Tyr Phe Thr Phe Leu
405 410 415
Arg Lys Val Asn Glu Gly Leu Ser Leu Pro Ser Ala Ile Asp Ile Ile
420 425 430
Ser Arg Ile Pro Val Asn Tyr Glu Asn Leu Ile Glu Ser Ala Phe Thr
435 440 445
Arg Ile His Ser Lys Lys Gly Val Glu Tyr Asp Tyr His Leu Ala Ile
450 455 460
Thr Leu Ile Pro Asp Met Arg Gln Glu Gln Phe Asp Lys Ile Lys Gly
465 470 475 480
Phe Phe Phe Asn Asn Gly Ile Leu His Lys Ala Ile Asn Ile Asn Asn
485 490 495
Leu Arg Asp Pro Ser Lys Asp Gln Lys Lys Leu Ile Glu Ser Met Ile
500 505 510
Leu Gln Ala Leu Tyr Ala Phe Gly Ile Tyr Phe Tyr Ser Leu Asp Asn
515 520 525
Leu Asn Tyr Asp Phe Ile Ile Gly Leu Asp Val Thr Arg Glu Met Asp
530 535 540
Lys Ser Gly Arg Tyr Tyr Gly Ile Ser Gly Ala Ala Val Val Gln Asn
545 550 555 560
Lys Asn Gly Gln Val Leu Lys Ile Ile Pro Ile Thr Ser Pro Gln Ser
565 570 575
Ser Ser Glu Thr Ala Asn Ile Asn Tyr Leu Ile Gly Asn Ile Gln Gln
580 585 590
Glu Ala Ala Ala Ile Leu Asn Arg Lys Gly Tyr Ala Asp Ile Leu Phe
595 600 605
Leu Arg Asp Gly Lys Val Pro Gly Gly Glu Leu Glu Gln Phe Lys Glu
610 615 620
Ile Ser Arg Lys Tyr Asn Tyr Arg Phe Thr Ile Ile Glu Ile Leu Lys
625 630 635 640
Arg Pro Leu Val Arg Phe Phe Trp Glu Asn Tyr Lys Glu His Thr Val
645 650 655
Lys Ser Pro Arg His Asn Tyr Tyr Phe Lys Ile Gly Asp Thr Tyr Tyr
660 665 670
Leu Thr Ala His Tyr Phe Thr Asn Tyr Leu Lys Val Pro Leu Lys Leu
675 680 685
Gly Asn Thr Tyr Phe Val Ala Arg Gly Lys Ile Ser Lys Asn Val Ile
690 695 700
Ser Arg Glu Asp Ile Met Thr Ile Thr Lys Leu Thr Lys Leu Asn Tyr
705 710 715 720
Ser Gln Pro Glu Asn Pro Asp Lys Met Lys Leu Pro Ala Pro Val His
725 730 735
Leu Ser His Arg Leu Ile Asn Tyr Glu Arg Arg Glu Leu Lys Phe Asn
740 745 750
Arg Tyr Glu Phe Leu Lys Glu Gly Ala Leu Tyr Phe Leu
755 760 765
<210> 23
<211> 710
<212> PRT
<213> artificial sequence
<400> 23
Pro Trp Arg Ser Asn Ala Val Arg Val Arg Met Asp Phe Glu Val Leu
1 5 10 15
Arg Arg Glu Asp Tyr His Asp Arg Gly Ala Ala Arg Gly Ala Val Lys
20 25 30
Asp His Leu Arg Glu Arg Glu Phe Ala Phe Gln Val Asp Thr Val Val
35 40 45
Tyr Ser Ala Gly Asp Arg Gly Glu Arg Val Ser Trp Asp Asp Leu Ser
50 55 60
Pro Thr Ala Arg Ala Tyr Ala Val Arg Ala Ala Leu Arg Leu Gly Leu
65 70 75 80
Glu Gly Leu Gly Phe Glu Leu Asp Thr Gly Tyr Ser Leu Leu Cys Asp
85 90 95
Arg Asp Phe Phe Glu Val Cys Tyr Gly Gly Arg Phe Asp Gly Glu Arg
100 105 110
Ile Pro Gly Val Tyr Ala Leu Gly Asn Trp Arg Glu Val Arg Asp Arg
115 120 125
Val Leu Arg Thr Leu Gly Arg Glu Tyr Gly Pro Val Glu Val Arg Leu
130 135 140
Gly Leu Glu Val Arg Ala Arg Ala Leu Gly Asp Gly Thr Val Leu Leu
145 150 155 160
Ser Val Asp Pro Arg Ala Arg Ala Ile Ser Arg Val Arg Leu Lys Asp
165 170 175
Leu Val Arg Asp Arg Gly Val Gly Trp Ala Glu Arg Val Leu Pro Gly
180 185 190
Thr Tyr Val Ile Pro Thr Asp Gly Gly Leu Thr Gly Arg Arg Leu Lys
195 200 205
Val Val Asp Ala Val Pro Ala Asp Glu Trp Glu Gly Glu Asp Gly Trp
210 215 220
Asp Leu Glu Arg Leu Arg Glu His Trp Ser Gly Tyr Gly Val Glu Val
225 230 235 240
Asp Pro Glu Val Val Val Thr Val Lys Val Gly Gly Gly Val Leu His
245 250 255
Tyr Pro Asp Asp Val Leu Arg Trp Gln Val Pro Val His Pro Val Thr
260 265 270
Glu Tyr Phe Arg Leu Gly Val Ala Asp Arg Val Ser Val Gly Arg Tyr
275 280 285
Leu Leu Asp Arg Gly Leu Gly Glu Phe Arg Arg Arg Phe Pro Asp Val
290 295 300
Ala Val Glu Val Arg Glu His Pro Gly Ser Thr Asp Thr Arg Arg Val
305 310 315 320
Arg Pro Pro Ala Val Val Ala Gly Gly Glu Lys Arg Gly Lys Arg Thr
325 330 335
Glu Leu Asn Asp Leu Leu Trp Asn Tyr Gly Pro Tyr Glu Gly Ala Gly
340 345 350
Glu Leu Asp Gly Glu Ala Val His Leu Val Ala Asp Arg Glu Leu Pro
355 360 365
Gly Arg Ala Gly Ile Ser Glu Arg Asp Leu Glu Arg Leu Leu Glu Leu
370 375 380
Val Val Gly Arg Leu Arg Arg Leu Leu Gly His Asp Val Glu Ala Gly
385 390 395 400
Asp Val Arg Val Ala Asp Ala Val Asp Leu Pro Asp Leu Val Gly Asp
405 410 415
Ala Asp Gly Pro Val Leu Val Gly Val Leu Ser Asp Asp Asp Arg Thr
420 425 430
Tyr Ala Arg Val Lys Arg Arg Asp Pro Leu Val Gln Cys Phe Thr Glu
435 440 445
Arg Val Leu Ser Asp Gly Lys Thr Val Lys Tyr Ala Ala Thr Val Leu
450 455 460
Ala Val Gly Ile His Cys Lys His Ala Gly Gln Pro Tyr Ala Val Arg
465 470 475 480
Ala Thr Ser Gly Pro Lys Asp Val Ala Val Val Gly Val Asp Val Ser
485 490 495
Arg Lys Val Glu Gly Gly Arg Val Val Glu Gly Arg Ala Cys Cys Ser
500 505 510
Cys Phe Val Val Asp Glu Asp Gly Leu Ile Glu His Gly Arg Thr Phe
515 520 525
Thr Val Pro Val Gly Glu Arg Gly Glu Thr Ser Gly Arg Thr Ala Glu
530 535 540
Ile Val Leu Glu Thr Ala Arg Glu Tyr Ser Asp Arg Val Val Tyr Leu
545 550 555 560
Arg Asp Gly Thr Val Pro Gly Glu Glu Leu Glu Ala Val Arg Glu Val
565 570 575
Gly Arg Glu Leu Gly Leu Asp Val Thr Val Val Glu Val Ile Lys Ser
580 585 590
Asp Pro Thr Val Tyr Ala Ile Glu Gly Glu Gly Trp Arg Ala Pro Arg
595 600 605
Gly Ala Tyr Val Arg Leu Asp Gly Ser Thr Val His Leu Cys Cys Ser
610 615 620
Pro Tyr Thr Pro Arg Arg Arg Gly Asp Lys Lys Pro Gly Thr Pro Arg
625 630 635 640
Pro Ile Ala Leu Arg Arg Arg Asp Asp Lys Leu Asp Gly Asp Leu Ile
645 650 655
Gly Leu Val His Asp Leu Thr Ala Ser Asn Trp Gly Asn Pro Ser Gly
660 665 670
Thr Trp Ser Arg Leu Pro Ala Pro Val Leu Tyr Ala Asp Arg Ala Ser
675 680 685
Arg Leu Ala Arg Tyr Gly Val Ser Val Gly Pro Gly Asp Pro Val Ser
690 695 700
Glu Arg Pro Trp Pro Val
705 710
<210> 24
<211> 734
<212> PRT
<213> artificial sequence
<400> 24
Asp Leu Leu Ser Asn Leu Arg Arg Ser Ser Ile Val Leu Asn Arg Phe
1 5 10 15
Tyr Val Lys Ser Leu Ser Gln Ser Asp Leu Thr Ala Tyr Glu Tyr Arg
20 25 30
Cys Ile Phe Lys Lys Thr Pro Glu Leu Gly Asp Glu Lys Arg Leu Leu
35 40 45
Ala Ser Ile Cys Tyr Lys Leu Gly Ala Ile Ala Val Arg Ile Gly Ser
50 55 60
Asn Ile Ile Thr Lys Glu Ala Val Arg Pro Glu Lys Leu Gln Gly His
65 70 75 80
Asp Trp Gln Leu Val Gln Met Gly Thr Lys Gln Leu Asp Cys Arg Asn
85 90 95
Asp Ala His Arg Cys Ala Leu Glu Thr Phe Glu Arg Lys Phe Leu Glu
100 105 110
Arg Asp Leu Ser Ala Ser Ser Gln Thr Glu Val Arg Lys Ala Ala Glu
115 120 125
Gly Gly Leu Ile Trp Trp Val Val Gly Ala Lys Gly Ile Glu Lys Ser
130 135 140
Gly Asn Gly Trp Glu Val His Arg Gly Arg Arg Ile Asp Val Ser Leu
145 150 155 160
Asp Ala Glu Gly Asn Leu Tyr Leu Glu Ile Asp Ile His His Arg Phe
165 170 175
Tyr Thr Pro Trp Thr Val His Gln Trp Leu Glu Gln Tyr Pro Glu Ile
180 185 190
Pro Leu Ser Tyr Val Arg Asn Asn Tyr Leu Asp Glu Arg His Gly Phe
195 200 205
Ile Asn Trp Gln Tyr Gly Arg Phe Thr Gln Glu Arg Pro Gln Asp Ile
210 215 220
Leu Leu Asp Cys Leu Gly Met Ser Leu Ala Glu Tyr His Leu Asn Lys
225 230 235 240
Gly Ala Thr Glu Glu Glu Val Gln Gln Ser Tyr Val Val Tyr Val Lys
245 250 255
Pro Ile Ser Trp Arg Lys Gly Lys Leu Thr Ala His Leu Ser Arg Arg
260 265 270
Leu Ser Pro Ser Leu Thr Met Glu Met Leu Ala Lys Val Ala Glu Asp
275 280 285
Ser Thr Val Cys Asp Arg Glu Lys Arg Glu Ile Arg Ala Val Phe Lys
290 295 300
Ser Ile Lys Gln Ser Ile Asn Gln Arg Leu Gln Glu Ala Gln Lys Thr
305 310 315 320
Ala Ser Trp Ile Leu Thr Lys Thr Tyr Gly Ile Ser Ser Pro Ala Ile
325 330 335
Ala Leu Ser Cys Asp Gly Tyr Leu Leu Pro Ala Ala Lys Leu Leu Ala
340 345 350
Ala Asn Lys Gln Pro Val Ser Lys Thr Ala Asp Ile Arg Asn Lys Gly
355 360 365
Cys Ala Lys Ile Gly Glu Thr Ser Phe Gly Tyr Leu Asn Leu Tyr Asn
370 375 380
Asn Gln Leu Gln Tyr Pro Leu Glu Val His Lys Cys Leu Leu Glu Ile
385 390 395 400
Ala Asn Lys Asn Asn Leu Gln Leu Ser Leu Asp Gln Arg Arg Val Leu
405 410 415
Ser Asp Tyr Pro Gln Asp Asp Leu Asp Gln Gln Met Phe Trp Gln Thr
420 425 430
Trp Ser Ser Gln Gly Ile Lys Thr Val Leu Val Val Met Pro Trp Asp
435 440 445
Ser His His Asp Lys Gln Lys Ile Arg Ile Gln Ala Ile Gln Ala Gly
450 455 460
Ile Ala Thr Gln Phe Met Val Pro Leu Pro Lys Ala Asp Lys Tyr Lys
465 470 475 480
Ala Leu Asn Val Thr Leu Gly Leu Leu Cys Lys Ala Gly Trp Gln Pro
485 490 495
Ile Gln Leu Glu Ser Val Asp His Pro Glu Val Ala Asp Leu Ile Ile
500 505 510
Gly Phe Asp Thr Gly Thr Asn Arg Glu Leu Tyr Tyr Gly Thr Ser Ala
515 520 525
Phe Ala Val Leu Ala Asp Gly Gln Ser Leu Gly Trp Glu Leu Pro Ala
530 535 540
Val Gln Gly Gly Glu Thr Phe Ser Gly Gln Ala Ile Trp Gln Thr Val
545 550 555 560
Ser Lys Leu Ile Ile Lys Phe Tyr Gln Ile Cys Gln Arg Tyr Pro Gln
565 570 575
Lys Leu Leu Leu Met Arg Asp Gly Leu Val Gln Glu Gly Glu Phe Gln
580 585 590
Gln Thr Ile Glu Leu Leu Lys Glu Arg Lys Ile Ala Val Asp Val Ile
595 600 605
Ser Val Arg Lys Ser Gly Ala Gly Arg Met Gly Gln Glu Ile Tyr Glu
610 615 620
Asn Gly Gln Leu Val Tyr Arg Asp Ala Ala Ile Gly Ser Val Ile Leu
625 630 635 640
Gln Pro Ala Glu Arg Ser Phe Ile Met Val Thr Ser Gln Pro Val Ser
645 650 655
Lys Thr Ile Gly Ser Ile Arg Pro Leu Arg Ile Val His Glu Tyr Gly
660 665 670
Ser Thr Asp Leu Glu Leu Leu Ala Leu Gln Thr Tyr His Leu Thr Gln
675 680 685
Leu His Pro Ala Ser Gly Phe Arg Ser Cys Arg Leu Pro Trp Val Leu
690 695 700
His Leu Ala Asp Arg Ser Ser Lys Glu Phe Gln Arg Ile Gly Gln Ile
705 710 715 720
Ser Val Leu Gln Asn Ile Ser Arg Asp Lys Leu Ile Ala Val
725 730
<210> 25
<211> 730
<212> PRT
<213> artificial sequence
<400> 25
Pro Met Arg Met Leu Gln Gln Glu Val Pro Val Ile Leu Asn Arg Phe
1 5 10 15
Leu Val Lys Glu Leu Thr Gln Glu Asp Leu Thr Phe Tyr Glu Tyr Asp
20 25 30
Cys Arg Pro Asn Pro Pro Pro Glu Leu Gly Glu Glu Gln Arg Ala Ile
35 40 45
Ala Arg Val Cys Asn Arg Leu Asp Val Ile Ala Ala Arg Leu Gly Ser
50 55 60
Arg Ile Ile Thr Gln Glu Arg Val Ser Pro Ser Gln Leu Lys Thr Pro
65 70 75 80
Glu Trp Glu Leu Glu Glu Arg Gly Leu Arg Val Leu Thr Cys Ala Asn
85 90 95
Ala Gln Glu Arg Ser Ala Leu Glu Ser Phe Glu Arg Lys Arg Ile Gly
100 105 110
Leu Arg Leu Lys Ser Gln Tyr Lys Lys Thr Glu Val Glu Trp Ile Gly
115 120 125
Gly Gly Leu Leu Trp Trp Val Thr Ala Gln Lys Gly Val Glu Leu Ser
130 135 140
Gly Glu Gly Trp Glu Ile His Arg Gly Arg Met Ile Asp Val Ala Val
145 150 155 160
Glu Pro Asp Gly Lys Leu Tyr Leu Glu Val Asp Ile His Tyr Arg Phe
165 170 175
Tyr Thr Pro Trp Thr Leu His Glu Trp Leu Glu Ser Tyr Pro Asp Val
180 185 190
Pro Ile Glu Ile Val Arg Asn Thr Tyr Phe Asp Ala Asn Gly Lys Arg
195 200 205
Leu Thr Trp Lys Tyr Leu Gly Ile Leu Ser Asn Gln Ser Pro Arg Glu
210 215 220
Ile Arg Leu Pro Glu Gln Asn Ile Ser Leu Ala Glu Tyr His Leu Gln
225 230 235 240
Lys Tyr Asn Ala Leu Val Glu Glu Val Glu Ser Ser Trp Val Val Glu
245 250 255
Val Ala Ser Lys Glu Arg Arg Tyr Pro His Leu Ser Arg Arg Leu Ser
260 265 270
Pro Ala Leu Thr Leu Glu Met Leu Ala Ser Leu Glu Asp Asn Arg Ser
275 280 285
Pro Gly Gly Lys Val Ser Ala Ala Val Ile Glu Cys Ile Arg Lys Ser
290 295 300
Leu Lys Glu Arg Phe Glu Glu Ser Glu Glu Thr Ala Arg Thr Ile Ile
305 310 315 320
Lys Glu Val Tyr Lys Leu Ser Pro Glu Glu Ile Lys Pro Leu Lys Thr
325 330 335
Gln Gly Tyr Ile Leu Pro Lys Pro Lys Leu Leu Gly Ser Gly Arg Arg
340 345 350
Pro Val Glu Asn Pro Ala Arg Val Arg Tyr Arg Gly Cys Ala Lys Val
355 360 365
Gly Glu Thr Lys Phe Ala Cys Leu Asn Leu Tyr Asp Asp Lys Arg Glu
370 375 380
Tyr Pro Ser Glu Val Leu Asn Cys Leu Leu Glu Val Ala Gln Lys Ser
385 390 395 400
Gly Ala Glu Ile Glu Val Asp Phe Tyr Ala Thr Gln Gln Asp Leu Pro
405 410 415
Lys Gly Asp Leu Ala Arg Lys Arg Phe Trp Gln Thr Trp Ala Glu Gln
420 425 430
Gly Ile Lys Thr Val Leu Val Val Met Pro Trp Ser Pro Asn Glu Arg
435 440 445
Lys Gln Arg Ile Arg Met Glu Ala Leu Glu Ala Gly Ile Ala Thr Gln
450 455 460
Phe Met Ile Pro Gly Ala Asp Pro Tyr Lys Ala Leu Asn Val Val Leu
465 470 475 480
Gly Leu Leu Cys Lys Ala Ala Trp Gln Pro Val Leu Leu Glu Pro Leu
485 490 495
Asp Asp Pro Val Gly Pro Glu Leu Ile Ile Gly Phe Asp Val Gly Thr
500 505 510
Asn Arg Arg Leu Tyr Tyr Gly Ala Ser Ala Phe Ala Val Leu Ala Asp
515 520 525
Gly Gln Ser Leu Gly Trp Glu Leu Pro Ala Val Gln Arg Gly Glu Thr
530 535 540
Phe Ser Gly Asp Ala Ile Tyr Gln Thr Val Ser Lys Leu Val Asp Arg
545 550 555 560
Phe Tyr Asp Lys Leu Ser Arg Tyr Pro Ser Lys Val Leu Leu Met Arg
565 570 575
Asp Gly Leu Val Gln Gly Gly Glu Phe Ser Arg Thr Ile Glu Glu Leu
580 585 590
Glu Lys Glu Lys Ile Ala Val Asp Ile Val Gly Ile Arg Lys Ser Gly
595 600 605
Thr Gly Arg Met Gly Ile Glu Glu Gly Lys Gly Lys Tyr Lys Asp Ala
610 615 620
Lys Ile Gly Thr Val Val Phe Asp Tyr Ser Arg Lys Ser Phe Thr Leu
625 630 635 640
Ile Thr Ser Gln Pro Ile Arg Lys Gly Gly Asn Ser Leu Gly Ser Ala
645 650 655
Arg Pro Leu Arg Ala Ile His Glu His Gly Lys Thr Pro Leu Glu Val
660 665 670
Leu Ala Leu Gln Thr Tyr His Leu Ser Gln Leu His Pro Ala Ser Gly
675 680 685
Phe Gln Ala Cys Arg Leu Pro Trp Val Leu His Phe Ala Asp Lys Ser
690 695 700
Gly Lys Glu Phe Gln Arg Leu Gly Asp Asn Ile Phe Ser Ile Leu Gln
705 710 715 720
Asn Ile Asp Arg Gln Lys Leu Ile Ala Val
725 730
<210> 26
<211> 706
<212> PRT
<213> artificial sequence
<400> 26
Asn Gln Tyr Tyr Ile Thr Glu Cys Met Ala Asn Glu Asn Ala Asn Asn
1 5 10 15
Ile Pro Leu His Ile Tyr Thr Val Ser Leu Leu Asn Pro Asn Gln Lys
20 25 30
Tyr Ser Phe Ala His His Ile Val Tyr Glu Leu Arg Lys Arg Asn Pro
35 40 45
Asn Val Thr Ile Ala Val His Gly Gln Tyr Ile Ala Ser Phe Gln Glu
50 55 60
Ile Ala His Trp Gly Asp His Glu Tyr Ile Lys His Glu Tyr Arg Ala
65 70 75 80
Ile Glu Cys Phe Asn Ala Thr Glu Arg Thr Val Leu Glu Arg Leu Leu
85 90 95
Lys Gln Glu Leu Ile Glu Arg Cys Lys Ser Asp Tyr Lys Ile Tyr Lys
100 105 110
Asp Leu Phe Cys Leu Lys Thr Glu Gln Ser Ile Glu Met Asn Glu Ile
115 120 125
Ile Val Tyr Pro Ala Ile Tyr Leu Ser Phe Thr Val Glu Glu Asn Gly
130 135 140
Asn Ile Leu Ile Gly Phe Glu Tyr Gln His Arg Phe Glu Tyr Lys Lys
145 150 155 160
Thr Leu Glu Asp Leu Leu Arg Asp Arg Ser Pro Leu Ile Lys Glu Gly
165 170 175
Val Glu Val Val Asp Ser Tyr Asn Lys Lys Ser Tyr Tyr Tyr Thr Phe
180 185 190
Val Glu Val Ala Pro Tyr Thr Ala Gly Glu Lys Ser Pro Tyr Leu Gln
195 200 205
Gln Ser Val Ile Asp Tyr Tyr Ile Thr Lys Asn Glu Lys Trp Lys Leu
210 215 220
Lys Gly Val His Asn Lys Thr Pro Ile Val His Val Arg Ser Gln Thr
225 230 235 240
Gly Asp Ile Phe Pro Tyr Leu Pro His Leu Leu Arg Leu Thr Cys Ser
245 250 255
Tyr Glu Gln Leu Met Pro Ser Thr Ala Lys Gln Val Asn Arg Ile Ile
260 265 270
Lys Leu Pro Pro Asn Lys Lys Met Pro Lys Leu Tyr Gln Glu Ile Phe
275 280 285
Arg Leu Leu Gln Tyr Gln Asp Met Leu Thr Phe Arg Lys Glu Asn Val
290 295 300
Arg Ala Ala Asn Leu Asn Tyr Asn Ile Phe Lys Leu Ser Pro Pro Leu
305 310 315 320
Met Lys Phe Gly Arg Asn Tyr Thr Thr Thr Lys Val Ser Asp Gly Leu
325 330 335
Gly Gln Ala Gly Val Tyr Glu Pro Lys Ser Val Thr Val Ser Tyr Phe
340 345 350
Val Asp Pro Glu Leu Asn Tyr Asp Gln Arg Lys Lys Asp Glu Ile Leu
355 360 365
Asp Phe Thr Lys Lys Leu Gln Asp Leu Ser Gly Lys Leu Gly Val Lys
370 375 380
Leu Asn Val Ser Lys Lys Pro Arg Gln Leu Phe Gly Val Leu Pro Val
385 390 395 400
Asp Phe Phe Lys Ser Glu Arg Leu Ser Phe Glu Leu Lys Ser Ile Thr
405 410 415
Asn Ala Phe Glu Gly Thr Ile Val Val Ile Gly Thr Glu Glu Asn Ile
420 425 430
Glu Arg Ala Tyr Met Ala Ile Lys Lys Glu Phe Gly Ala Lys Ala Asp
435 440 445
Ile Met Thr Gln Phe Val Ile Phe Asp Ser Ser Ile Val Asn Asn Ser
450 455 460
Phe Tyr Tyr Tyr Asn Val Leu Leu Gly Ile Tyr Ala Lys Ser Gly Val
465 470 475 480
Gln Pro Trp Ile Leu Leu Asp His Met Asn Ser Asp Cys Phe Ile Gly
485 490 495
Leu Asp Val Ser His Glu Gln Gly Lys His Ala Ser Gly Ile Ile Gln
500 505 510
Val Ile Gly Lys Asp Gly Arg Ile Ile Lys Gln Lys Ser Val Met Ala
515 520 525
Thr Glu Ala Gly Glu Thr Ile Ala Arg Cys Thr Met Glu Glu Ile Ile
530 535 540
Asn Glu Ser Ile Phe Ser Tyr Glu Lys Met Tyr Gly Met Lys Pro Ser
545 550 555 560
His Ile Thr Phe His Arg Asp Gly Val Cys Arg Glu Asp Leu Ala His
565 570 575
Leu Thr Gln Tyr Met Gln Ser Phe Gln Ile Pro Phe Asp Phe Val Glu
580 585 590
Ile Ile Lys Lys Pro Arg Arg Arg Met Ala Val Tyr Lys Asn Lys Ser
595 600 605
Trp Phe Thr Glu Gln Gly Leu Cys Tyr Ala Lys Glu Arg Met Ala Tyr
610 615 620
Leu Cys Ala Thr Asp Pro Arg Glu Ser Val Gly Met Ala Gln Val Val
625 630 635 640
Lys Ile Val Gln Lys Thr Asn Cys Leu Ser Ile Arg Asp Ile Val Ser
645 650 655
Asp Ala Tyr Lys Leu Ser Phe Met His Ile His Ser Met Leu Lys Thr
660 665 670
Arg Leu Pro Ile Thr Ile His Tyr Ala Asp Leu Ser Ser Thr Phe His
675 680 685
Asn Arg Gly Leu Ile His Pro Arg Ser Val His Glu Arg Ala Leu Pro
690 695 700
Phe Val
705
<210> 27
<211> 604
<212> PRT
<213> artificial sequence
<400> 27
Lys Lys Gln Leu Glu Arg Leu Ala His Pro Asn Tyr Met Met Asn Arg
1 5 10 15
Gly Lys Phe Arg Ser Lys Gln Ala His Pro Lys Ser Thr Ser Gly Leu
20 25 30
Leu Ile Tyr Pro Ala Leu Asp Leu Asn Val Asn Val Ser Glu Thr Ala
35 40 45
Glu Ile Val Phe Gly Phe Asp Leu Thr His Gln Phe Glu Tyr Arg Glu
50 55 60
Asn Leu Leu Gln Gln Ile Lys Arg Asp Pro Lys Ser Val Ser Ala Gly
65 70 75 80
Met Arg Val Ile Asp Ser Thr His Pro Lys Ser Tyr Glu Tyr Glu Phe
85 90 95
Val Glu Val Ala Pro Tyr Arg Ala Asn Glu Val Ser Pro Ile Met Arg
100 105 110
Cys Ser Ile Ile Asp Tyr Phe Ala Lys Lys Asp Pro Lys Arg Val Ile
115 120 125
Glu Pro Asp Ala Leu Val Val His Val Lys Asp Arg Asn Asn Gln Ile
130 135 140
Leu Ile Tyr Leu Pro Glu Gln Leu Lys Gln Ser Cys Ser Phe Glu Thr
145 150 155 160
Ile Pro Ala Arg His Leu Gly Ala Val Ser Arg Ile Ile Lys Leu Ser
165 170 175
Pro Asp Ala Arg Met Ser Lys Leu Met Pro Glu Ala Leu Ala Leu Ile
180 185 190
Gly Arg Leu Pro Met Leu Gln Phe Glu Arg Gln Asp Val Arg Ala Ala
195 200 205
Arg Leu Gly Tyr Ser Ile Gln Thr Leu Pro Ser Pro Arg Leu Arg Phe
210 215 220
Gly Lys Gly Arg Thr Thr Ser Tyr Ala Lys Thr Gly Leu Lys Gln Gly
225 230 235 240
Gly Val Tyr Glu Thr Gly Glu Ala Thr Val Ser Phe Phe Val Asp Pro
245 250 255
Lys Leu Arg Asp His Gln Lys Leu Gln Val Leu Glu Phe Ile Asn Lys
260 265 270
Leu Lys Thr Thr Ser Glu Arg Phe Gly Val Thr Leu Asn Val Ser His
275 280 285
Lys Pro Lys Gly Leu Ser Gln Lys Leu Pro Ser Asp Leu Leu Gln Thr
290 295 300
Glu Asp Ile Leu Tyr Gln Leu Lys Asn Ile Pro Gln His Phe Glu Gly
305 310 315 320
Val Val Val Val Ile Ala Glu Glu Ala Ser Leu Gln His Ser Tyr Gln
325 330 335
Ala Ile Lys Arg Gln Phe Gly Gly Lys Gln Asp Val Val Thr Gln Cys
340 345 350
Val Glu Leu His Asp Arg Val Leu Asn Ser Glu Asp Thr Leu Tyr Asn
355 360 365
Ile Leu Leu Gly Ile Tyr Val Lys Ala Gly Leu Gln Pro Trp Ile Leu
370 375 380
Gly Glu Pro Leu His Ser Asp Cys Phe Val Gly Leu Asp Val Ser His
385 390 395 400
Glu Asn Gly Lys His Ala Ala Gly Ile Ile Gln Ile Ile Gly Lys Asp
405 410 415
Gly Ala Met Ile Lys Gln Lys Ala Leu Ser Thr Ser Glu Ala Gly Glu
420 425 430
Lys Ile Ser Ser Glu Thr Met Arg Glu Ile Val Tyr Asp Thr Leu His
435 440 445
Ala Phe Glu Glu Gln Tyr Gly His Ala Pro Lys His Ile Thr Phe His
450 455 460
Arg Asp Gly Phe Gly Arg Glu Asp Leu Thr Leu Ile Asp Ser Ile Leu
465 470 475 480
Ser Pro Arg Glu Ile Gln Phe Asp Tyr Val Glu Ile Leu Lys Asn Ile
485 490 495
Asn Arg Arg Met Ala Ile His Glu Asp Glu Trp Lys Thr Ser Gln Gly
500 505 510
Leu Ser Tyr Thr Lys Glu Arg Met Gly Tyr Leu Leu Ser Thr Asn Pro
515 520 525
His Ala Arg Val Gly Met Ala Lys Pro Leu Lys Val Val Gln Gln Thr
530 535 540
Thr Thr Leu Pro Phe Glu Ala Ile Leu Thr Asp Val Tyr Arg Leu Ser
545 550 555 560
Phe Met His Val His Ser Leu Leu Lys Thr Arg Leu Pro Ile Thr Thr
565 570 575
His Tyr Ala Asp Leu Ser Ser Thr Phe His Asn Arg Gly Leu Leu Asn
580 585 590
Ala Asn Thr Glu His Glu Glu Ala Leu Pro Phe Val
595 600
<210> 28
<211> 763
<212> PRT
<213> artificial sequence
<400> 28
Asn Thr Thr Ser Gln Ala Pro Gln Asn Ser Thr Ser Ser Ser Ile Tyr
1 5 10 15
Leu Ser Glu Ile Phe Pro Leu Thr Ile Leu Lys Pro Asn Leu Ile Cys
20 25 30
Phe Arg Leu Thr Pro Glu Val Asp Arg Glu Val Gly Asn Arg Leu Ser
35 40 45
Trp Arg Phe Ser Gln Lys Phe Ala Glu Ile Val Val Ile Trp Glu Asn
50 55 60
Lys Tyr Phe Trp Val Leu Ala Lys Pro Thr Gln Lys Met Pro Ser Pro
65 70 75 80
Glu Gln Trp Arg Gln Ala Leu Gly Glu Ile Leu Glu Gln Leu Lys Glu
85 90 95
Asp Ile Gly Asp His Tyr Tyr Ser Ile Gln Trp Val Arg Asp Pro Gln
100 105 110
Val Thr Ala Ser Thr Leu Ala Gln Leu Ala Val Arg Val Leu Lys Ile
115 120 125
Arg Lys Pro Phe Ser Pro Asp Ile Ile Phe Ser Glu Asn Gln Val Gln
130 135 140
Val Gln Ser Glu Val Asp Phe Trp Pro Glu Thr Ile Glu Leu Ala Asn
145 150 155 160
Thr Leu Thr Pro Ala Ile Thr Leu Thr Leu Lys Ser Arg Phe Leu Tyr
165 170 175
Arg Gly Thr Leu Ala Glu Phe Tyr Ala Asn His Pro Tyr Arg Asn Lys
180 185 190
Pro Lys Glu Leu Leu Val Gly Leu Lys Val Arg Asp Arg Glu Thr Asn
195 200 205
Ser Ser Ala Thr Ile Val Glu Ile Ala Ala Ile Asp Glu Asp Arg Arg
210 215 220
Lys Glu Leu Ile Glu Lys Ala Thr Gly Ala Val Ser Arg Gln Ala Leu
225 230 235 240
Glu Glu Ala Pro Asp Asp Gln Pro Leu Val Ser Val Arg Phe Gly Lys
245 250 255
Asn Gln Lys Leu Phe Asp Tyr Pro Met Glu Ala Leu Cys Pro Ser Ile
260 265 270
Thr Lys Glu Thr Ala Ser Lys Phe Asp Val Asn Tyr Gly Asp Leu Ile
275 280 285
Lys Gln Thr Lys Pro Pro Tyr Gln Glu Arg Gln Asn His Leu Thr Gln
290 295 300
Ser Lys Gln Lys Ala Glu Glu Ser Leu Ala Val Tyr Gly Phe Gln Ile
305 310 315 320
Asp Lys Ser Ile Asn Asn Leu Asp Tyr Pro Ser Leu Phe Gln Thr Leu
325 330 335
Gln Phe Asn Leu Glu Asp Thr Glu Leu Leu Phe Gly Lys Asp Ser Ser
340 345 350
Gly Lys His Phe Val Ser Lys Arg Gly Ser Val Leu Lys Gly Leu Ser
355 360 365
Gln Gly Gly Val Tyr Arg Arg His Gln Asp Tyr Glu Asn Tyr Ser Thr
370 375 380
Pro Ile Arg Ile Ser Leu Leu Asn Leu Cys Asn Ser Lys Val Gly Lys
385 390 395 400
Phe Val Ser Gln Val Glu Glu Arg Leu Lys Gln Tyr Lys Phe Glu Thr
405 410 415
Ile Arg Phe Glu Lys Asp Ser Leu Asp Arg Arg Lys Glu Ile Lys Val
420 425 430
Asp Asn Leu Asp Ser Ala Glu Ala Arg Val Ala Val Glu Lys Ala Leu
435 440 445
Asp Glu Leu Met Val Ile Pro Thr Asn Ile Val Leu Thr Phe Leu Pro
450 455 460
Glu Ser Asp Arg His Thr Asp Asp Thr Glu Asp Gly Ser Phe Tyr Ser
465 470 475 480
Phe Val Ser Ser Arg Leu Leu Arg Arg Gly Ile Ser Ser Gln Val Ile
485 490 495
Tyr Glu Asp Thr Leu Lys Asn Pro Asn Asn Tyr Ser Tyr Ile Leu Asn
500 505 510
Gln Val Ile Pro Gly Ile Leu Ala Lys Leu Gly Asn Leu Pro Phe Ile
515 520 525
Leu Ala Lys Pro Leu Glu Ile Ala Asp Tyr Phe Ile Gly Leu Asp Ile
530 535 540
Ser Arg Thr Pro Lys Lys Arg Lys Ser Gly Ser Leu Asn Val Cys Ala
545 550 555 560
Ser Val Arg Leu Tyr Gly Lys Tyr Gly Glu Phe Ile Arg Tyr Arg Leu
565 570 575
Glu Asp Ala Leu Thr Gln Gly Glu Glu Ile Asp Lys Arg Thr Leu Glu
580 585 590
Arg Phe Leu Pro Ala Ala Asp Leu Ser Gly Lys Thr Val Leu Ile Tyr
595 600 605
Arg Asp Gly Arg Phe Cys Gly Asp Glu Ile Lys His Leu Arg Glu Arg
610 615 620
Ala Lys Ala Met Gly Ser Lys Phe Ile Leu Val Glu Cys Ile Lys Ser
625 630 635 640
Gly Ile Pro Arg Leu Tyr Glu Val Gln Glu Leu Thr Val Lys Asp Lys
645 650 655
Lys Lys Pro Ile Leu Lys Ala Pro Pro Lys Gly Leu Ala Leu Arg Leu
660 665 670
Ser Ser His Glu Val Met Leu Val Thr Thr Glu Val Lys Ser Glu Lys
675 680 685
Met Gly Leu Pro Asn Pro Leu Arg Leu Lys Val Ile Pro Glu Glu Gly
690 695 700
Gln Gln Val Ser Leu Glu Ser Leu Val Glu Ala Thr Leu Lys Leu Thr
705 710 715 720
Leu Leu His His Gly Ser Leu Lys Glu Pro Arg Leu Pro Ile Pro Leu
725 730 735
Tyr Gly Ser Asp Ile Ile Ala Tyr Arg Arg Leu Gln Gly Ile Ser Pro
740 745 750
Gly Glu Leu Asp Gly Asp Arg Gln Phe Trp Leu
755 760
<210> 29
<211> 745
<212> PRT
<213> artificial sequence
<400> 29
Asn Leu Leu Gln Lys Lys Val Glu Val Thr Leu Asn Arg Phe Phe Val
1 5 10 15
Lys Glu Leu Thr Gln Glu Glu Leu Thr Phe Tyr Glu Tyr Ser Cys Arg
20 25 30
Pro Asn Pro Leu Pro Asp Leu Gly Glu Glu Gln Arg Ala Leu Ser Lys
35 40 45
Ile Cys Asn Gln Leu Gly Val Met Ala Val Arg Leu Gly Asn Arg Ile
50 55 60
Ile Thr Arg Glu Lys Val Pro Ala Ser Lys Leu Lys Thr Glu Glu Trp
65 70 75 80
Glu Leu Glu Glu Leu Gly Ser Lys Ala Leu Asp Cys Thr Asp Pro Thr
85 90 95
Glu Arg Gln Ala Leu Glu Thr Phe Glu Arg Lys Lys Leu Asp Trp Ser
100 105 110
Leu Arg Ser Lys Tyr Lys Arg Thr Glu Ile Glu Arg Ser Thr Gly Gly
115 120 125
Gly Leu Ile Trp Trp Val Thr Gly Leu Glu Gly Val Glu Arg Ile Glu
130 135 140
Asp Ser Glu Gly Val Lys Pro Leu Cys Gly Asp Gly Trp Glu Val His
145 150 155 160
Arg Gly Arg Glu Leu Asp Val Val Ile Arg Gln Asp Lys Lys Leu Tyr
165 170 175
Leu Glu Ile Asp Ile Arg Tyr His Phe Tyr Ser Pro Trp Thr Leu His
180 185 190
Glu Trp Leu Glu Asn Tyr Pro Asp Val Ser Ile Glu Ile Val Arg Asn
195 200 205
Thr Tyr Arg Thr Lys Asn Asn Lys Tyr Pro Thr Trp Glu Tyr Arg Gly
210 215 220
Ile Ile Ser Asn Gln Ser Pro Arg Glu Val Trp Leu Ala Glu Leu Asn
225 230 235 240
Thr Ser Leu Ala Asp Tyr His Val Gln Lys Tyr Gly Ala Thr Pro Glu
245 250 255
Glu Val Asp Gly Ser Leu Val Val Gln Val Val Ser Arg Glu Arg Asn
260 265 270
Phe Arg Gln Lys Ala Glu Pro Ile Leu His Leu Ser Arg Arg Leu Ser
275 280 285
Pro Val Leu Thr Leu Glu Met Leu Ala Ser Ile Glu Asp Gln Arg Trp
290 295 300
Thr Gly Lys Lys Val Ser Ser Leu Val Ser Glu His Ile Arg Lys Ser
305 310 315 320
Leu Glu Glu Arg Leu Lys Glu Ser Lys Glu Thr Ala Lys Thr Ile Ile
325 330 335
Glu Asn Val Tyr Asn Ile Ser Asp Phe Gln Ala Asp Pro Leu Lys Ala
340 345 350
Glu Gly Tyr Ile Met Pro Ser Pro Arg Leu Leu Gly Phe Gly His Arg
355 360 365
Gln Val Gln Asn Pro Ala Arg Val Arg Tyr Gln Gly Cys Ala Arg Val
370 375 380
Gly Glu Thr Lys Phe Gly Leu Leu Asn Leu Asp Asp Asn Lys Arg Glu
385 390 395 400
Tyr Pro Thr Glu Val Arg Lys Cys Leu Leu Glu Val Ala Lys Lys Ser
405 410 415
Gly Ala Arg Val Glu Ile Asp Phe Tyr Ala Thr Arg Gln Asp Leu Pro
420 425 430
Glu Gly Asp Leu Ala Gln Gln Arg Phe Trp Gln Ser Trp Ala Asp Lys
435 440 445
Gly Ile Lys Thr Val Leu Val Val Met Pro Leu Ser Pro Asn Glu His
450 455 460
Lys Gln Lys Ile Arg Leu Gln Ala Leu Arg Ala Gly Ile Ala Thr Gln
465 470 475 480
Phe Met Ile Pro Gly Ala Asp Pro Tyr Lys Ala Leu Asn Val Val Leu
485 490 495
Gly Leu Leu Cys Lys Ala Ala Trp Gln Pro Val Leu Leu Glu Pro Leu
500 505 510
Asp His Pro Glu Cys Ser Glu Leu Thr Ile Gly Phe Asp Val Gly Thr
515 520 525
Asn Arg Glu Leu Tyr Tyr Gly Thr Ser Ala Phe Ala Val Leu Ala Asn
530 535 540
Gly Gln Ser Leu Gly Trp Glu Leu Pro Asp Ile Gln Arg Gly Glu Thr
545 550 555 560
Phe Ser Gly Glu Ala Ile Tyr Gln Thr Val Ser Lys Leu Val Asn Arg
565 570 575
Phe Tyr Asn Lys Phe His Arg Tyr Pro Arg Lys Val Leu Leu Met Arg
580 585 590
Asp Gly Leu Val Gln Arg Gly Glu Phe Asp Lys Thr Ile Glu Glu Leu
595 600 605
Arg Lys Glu Lys Ile Ala Val Asp Ile Val Gly Val Arg Lys Ser Gly
610 615 620
Thr Val Arg Met Gly Arg Glu Glu Lys Gly Ser Tyr Arg Asp Ala Ala
625 630 635 640
Met Gly Thr Val Ile Phe Asp His Glu Arg Arg Ser Phe Met Leu Val
645 650 655
Thr Ser Gln Pro Ile Lys Lys Ser Ser Val Pro Ile Gly Ser Ala Arg
660 665 670
Pro Leu Arg Val Val His Glu His Gly Asn Thr Pro Leu Glu Val Leu
675 680 685
Ala Ile Gln Thr Tyr His Leu Ser Gln Leu His Pro Ala Ser Gly Phe
690 695 700
Gln Ala Cys Arg Leu Pro Trp Val Leu His Phe Ala Asp Lys Ser Ser
705 710 715 720
Lys Glu Phe Gln Arg Ile Gly Asn Ser Ile Phe Ser Val Leu Gln Asn
725 730 735
Ile Asn Arg Glu Lys Leu Ile Ala Val
740 745
<210> 30
<211> 747
<212> PRT
<213> artificial sequence
<400> 30
Asn Asn Leu Thr Phe Glu Ala Phe Glu Gly Ile Gly Gln Leu Asn Glu
1 5 10 15
Leu Asn Phe Tyr Lys Tyr Arg Leu Ile Gly Lys Gly Gln Ile Asp Asn
20 25 30
Val His Gln Ala Ile Trp Ser Val Lys Tyr Lys Leu Gln Ala Asn Asn
35 40 45
Phe Phe Lys Pro Val Phe Val Lys Gly Glu Ile Leu Tyr Ser Leu Asp
50 55 60
Glu Leu Lys Val Ile Pro Glu Phe Glu Asn Val Glu Val Ile Leu Asp
65 70 75 80
Gly Asn Ile Ile Leu Ser Ile Ser Glu Asn Thr Asp Ile Tyr Lys Asp
85 90 95
Val Ile Val Phe Tyr Ile Asn Asn Ala Leu Lys Asn Ile Lys Asp Ile
100 105 110
Thr Asn Tyr Arg Lys Tyr Ile Thr Lys Asn Thr Asp Glu Ile Ile Cys
115 120 125
Lys Ser Ile Leu Thr Thr Asn Leu Lys Tyr Gln Tyr Met Lys Ser Glu
130 135 140
Lys Gly Phe Lys Leu Gln Arg Lys Phe Lys Ile Ser Pro Val Val Phe
145 150 155 160
Arg Asn Gly Lys Val Ile Leu Tyr Leu Asn Cys Ser Ser Asp Phe Ser
165 170 175
Thr Asp Lys Ser Ile Tyr Glu Met Leu Asn Asn Gly Leu Asp Val Val
180 185 190
Gly Leu Gln Val Lys Asn Arg Trp Thr Asn Ser Asn Gly Asn Ile Phe
195 200 205
Ile Glu Glu Val Leu Asp Lys Ser Ile Ser Glu Pro Gly Thr Ser Gly
210 215 220
Lys Leu Gly Gln Ser Leu Ile Asp Tyr Tyr Ile Asn Gly Asn Gln Lys
225 230 235 240
Tyr Arg Val Glu Lys Phe Thr Asp Glu Asp Lys Lys Ala Lys Val Ile
245 250 255
Lys Ala Lys Ile Lys Asn Lys Thr Tyr Asn Tyr Ile Pro Gln Ala Leu
260 265 270
Thr Pro Val Ile Thr Arg Glu Tyr Leu Ser His Thr Asp Lys Lys Phe
275 280 285
Ser Lys Gln Ile Glu Asn Val Ile Lys Met Asp Met Asn Tyr Arg Tyr
290 295 300
Gln Thr Leu Lys Ser Phe Val Glu Asp Ile Gly Val Ile Lys Glu Leu
305 310 315 320
Asn Asn Leu His Phe Lys Asn Gln Tyr Tyr Thr Asn Phe Asp Phe Met
325 330 335
Gly Phe Glu Ser Gly Ile Leu Glu Glu Pro Val Leu Met Gly Ala Asn
340 345 350
Gly Lys Ile Lys Asp Lys Lys Gln Ile Phe Ile Asn Gly Phe Phe Lys
355 360 365
Asn Pro Lys Glu Asn Val Lys Phe Gly Val Leu Tyr Pro Glu Gly Cys
370 375 380
Met Glu Asn Ala Gln Ser Ile Ala Arg Ser Ile Leu Asp Phe Ala Thr
385 390 395 400
Ala Gly Lys Tyr Asn Lys Gln Glu Asn Lys Tyr Ile Ser Lys Asn Leu
405 410 415
Met Asn Ile Gly Phe Lys Pro Ser Glu Cys Ile Phe Glu Ser Tyr Lys
420 425 430
Leu Gly Asp Ile Thr Glu Tyr Lys Ala Thr Ala Arg Lys Leu Lys Glu
435 440 445
His Glu Lys Val Gly Phe Val Ile Ala Val Ile Pro Asp Met Asn Glu
450 455 460
Ser Glu Val Glu Asn Pro Tyr Asn Pro Phe Lys Lys Val Trp Ala Lys
465 470 475 480
Leu Asn Ile Pro Ser Gln Met Ile Thr Leu Lys Thr Thr Glu Lys Phe
485 490 495
Lys Asn Ile Val Asp Lys Ser Gly Leu Tyr Tyr Leu His Asn Ile Ala
500 505 510
Leu Asn Ile Leu Gly Lys Ile Gly Gly Ile Pro Trp Ile Ile Lys Asp
515 520 525
Met Pro Gly Asn Ile Asp Cys Phe Ile Gly Leu Asp Val Gly Thr Arg
530 535 540
Glu Lys Gly Ile His Phe Pro Ala Cys Ser Val Leu Phe Asp Lys Tyr
545 550 555 560
Gly Lys Leu Ile Asn Tyr Tyr Lys Pro Thr Ile Pro Gln Ser Gly Glu
565 570 575
Lys Ile Ala Glu Thr Ile Leu Gln Glu Ile Phe Asp Asn Val Leu Ile
580 585 590
Ser Tyr Lys Glu Glu Asn Gly Glu Tyr Pro Lys Asn Ile Val Ile His
595 600 605
Arg Asp Gly Phe Ser Arg Glu Asn Ile Asp Trp Tyr Lys Glu Tyr Phe
610 615 620
Asp Lys Lys Gly Ile Lys Phe Asn Ile Ile Glu Val Lys Lys Asn Ile
625 630 635 640
Pro Val Lys Ile Ala Lys Val Val Gly Ser Asn Ile Cys Asn Pro Ile
645 650 655
Lys Gly Ser Tyr Val Leu Lys Asn Asp Lys Ala Phe Ile Val Thr Thr
660 665 670
Asp Ile Lys Asp Gly Val Ala Ser Pro Asn Pro Leu Lys Ile Glu Lys
675 680 685
Thr Tyr Gly Asp Val Glu Met Lys Ser Ile Leu Glu Gln Ile Tyr Ser
690 695 700
Leu Ser Gln Ile His Val Gly Ser Thr Lys Ser Leu Arg Leu Pro Ile
705 710 715 720
Thr Thr Gly Tyr Ala Asp Lys Ile Cys Lys Ala Ile Glu Tyr Ile Pro
725 730 735
Gln Gly Val Val Asp Asn Arg Leu Phe Phe Leu
740 745
<210> 31
<211> 744
<212> PRT
<213> artificial sequence
<400> 31
Ser Gln Asp Ser Arg Ser Thr Glu Val Glu Arg Gln Ala Glu Ile Gln
1 5 10 15
Pro Gly Thr Tyr Leu Leu Asn Gly Arg Gly Glu Ile Gln Leu Asp Glu
20 25 30
Val Asp Ala Phe Gln Tyr Asp Leu Lys Val Ser Gly Gly Val Glu Gln
35 40 45
Tyr Trp Asp Arg Glu Gln Phe Thr Ser Ser Ala Ala Tyr Tyr Leu Asp
50 55 60
Gln Glu His Gly Ser Pro Val Ala Glu Ile Gly Lys Met Asn Val Leu
65 70 75 80
Ser Lys Thr Asp Leu Ser Arg Ser Val Arg Val Trp Gln Arg Asn Val
85 90 95
Thr Pro Ile Asn Arg Gln Ser Val Thr Leu Thr Ala Ala Gln Pro Glu
100 105 110
Asp Arg Glu Lys Ile Lys Ser Phe Val Gln Ser Cys Phe Lys Arg Ala
115 120 125
Val Pro Thr Glu Lys Tyr Ser Phe Arg Phe Leu Asn Lys Ile Val Arg
130 135 140
Asp Glu Pro Glu Phe Thr Thr Gly Ser Glu Gly Phe Ser Ala His Pro
145 150 155 160
Lys His Asp Val Lys Ile Gln Val Thr Ala Asp Gly Asn Val Leu Val
165 170 175
His Val Asp Ser Gly Phe Ser Ile Arg Ser Asn Ser Thr Leu Asp Glu
180 185 190
Ile Tyr Ser Glu Gln Asp Asn Pro Tyr Gly Lys Arg Val Ala His Asp
195 200 205
Pro Glu Arg Tyr Gly Thr Gln Gly Gln Gly Thr Leu Arg Gly Trp Ser
210 215 220
Asp Tyr Arg Tyr Thr Asp His Ile Ser Asp Ala Gly Ser Ser Val Asn
225 230 235 240
Glu Met His Lys Gly Val Ala Asp Glu Glu Trp Arg Gln Arg Leu Ala
245 250 255
Glu Glu Asn Pro Arg Leu Leu Lys Val Glu Tyr Gly Asn Lys Thr Arg
260 265 270
Arg Gln Ala Pro His Phe Leu Arg Leu Ser Pro Arg Ile Glu Gln Val
275 280 285
Gln Asp Gln Asp Arg Glu Phe Tyr Ser Arg Phe Asn Ser Arg Ser Ala
290 295 300
Met Met Pro Asp Glu Arg Phe Glu Leu Ser Lys Glu Phe Leu Gln Asn
305 310 315 320
Val Ser Arg Leu Pro Val Leu Asp Met Glu Leu Glu Pro Gly Pro Val
325 330 335
Asn Ser Ser Tyr Glu Leu Leu Glu Met Arg Glu Glu Asn Arg Leu Val
340 345 350
Phe Gly Gly Lys Gln Arg Ala Arg Asp Pro Gly Ser Gly Leu Arg Glu
355 360 365
Asn Gly Val Tyr Gln Ser Pro Ser Gln Tyr Arg Leu Gly Val Leu Thr
370 375 380
Pro Glu Arg Trp Gly Glu Lys Ala Ser Glu Leu Ile Pro Leu Ile Val
385 390 395 400
Ser Gly Leu Asn Asp Leu Ser Ala Ser Ala Gly Val Arg Ala Tyr Gly
405 410 415
Tyr Glu Leu Gly Asp Val Ser Asn Tyr Thr Pro Val Val Gln Asp Leu
420 425 430
His Glu Glu Thr Asp Ala Val Leu Ala Val Val Pro Asn Lys Gly Val
435 440 445
Ala Glu Asp Phe Gly Ile Asp Asp Pro Tyr Lys Glu Leu Lys Arg Thr
450 455 460
Leu Leu Arg Lys Gly Ile Pro Thr Gln Met Met Gln Lys Ser Thr Val
465 470 475 480
Asp Glu Ile Val Gly Gln Lys Ala Gly Ile Gly Asn Asp Lys Phe Leu
485 490 495
Asn Ala Leu Ser Ala Val Val Ala Lys Val Gly Gly Thr Pro Trp Gln
500 505 510
Ile Asp Ser Leu Pro Gly Lys Thr Asp Ala Phe Met Gly Leu Asp Val
515 520 525
Thr Tyr Asp Glu Ser Ser Glu Gln His Ala Gly Ala Ser Ala Ser Val
530 535 540
Val Leu Ala Asp Gly Thr Thr Phe Ala Ala Glu Ser Thr Thr Gln Gln
545 550 555 560
Gly Gly Glu Lys Phe Ser Ala Arg His Val Glu Gln Phe Val Arg Asp
565 570 575
Leu Val Phe Asp Phe Ala Gly Glu Gln Gly Arg Asp Ile Asp Arg Leu
580 585 590
Cys Ile Met Arg Asp Gly Lys Ile Ser Glu Asp Ile Asp Ala Val Arg
595 600 605
Glu Gly Leu Ser Gly Ile Glu Ala Glu Ile Asp Ile Val Gly Ile Arg
610 615 620
Lys Ser Gly Gln Pro Arg Ile Ala Glu Phe Asp Gly Thr Arg Phe Arg
625 630 635 640
Ile Ala Glu Lys Gly Val Gly Phe Val Asp Ala Asp Arg Ser Gln Ser
645 650 655
Ile Ile His Ala Phe Gly Lys Pro Glu Ile His Asp Asp Asn Pro Val
660 665 670
Gly Thr Pro Arg Thr Phe Arg Leu Thr Lys Asp Ser Gly Pro Thr Asp
675 680 685
Val Glu Thr Leu Thr Arg Gln Ala Tyr Trp Leu Ser Glu Ile His Phe
690 695 700
Gly Ser Pro Val Arg Ser Pro Arg Leu Pro Val Pro Ile Glu Tyr Ala
705 710 715 720
Asp Met Ala Ala Glu Tyr Val Arg Glu Glu Tyr Val Ser Pro Gly Thr
725 730 735
Val Ile Glu Gly Pro Ala Tyr Ile
740
<210> 32
<211> 1047
<212> PRT
<213> artificial sequence
<400> 32
Ser Asp Val Val Glu Lys Val Gln Trp Ala Ala Ile Pro Gln Met Ser
1 5 10 15
Ile Asp Ala Phe Val Arg Ser Ile Ala Val Asn Gln Asn Arg Pro Val
20 25 30
Cys Leu Leu Leu Gly Ala Gly Ala Ser Ile Thr Ser Gly Met Pro Ser
35 40 45
Ala Gln Arg Cys Ile Trp Glu Trp Lys Arg Asp Ile Phe Ile Thr Lys
50 55 60
Asn Pro Thr Leu Arg Asp Ser Leu Asp Glu Leu Ser Leu Pro Gly Thr
65 70 75 80
Arg Arg Ile Ile Gln Ser Trp Leu Asp Leu Gln Ala Arg Tyr Pro Val
85 90 95
Glu Gly Ser Pro Asp Glu Tyr Ser Phe Tyr Ala Glu Glu Cys Tyr Pro
100 105 110
Thr Ser Leu Asp Arg Arg Thr Phe Phe His Arg Phe Ile Ser Glu Ala
115 120 125
Lys Pro His Ile Gly Tyr Lys Leu Thr Ala Leu Leu Ala Glu Ala Gly
130 135 140
Cys Val Arg Thr Ile Trp Thr Thr Asn Phe Asp Gly Leu Val Ala Arg
145 150 155 160
Ala Cys Thr Ala Ala Asp Val Val Cys Val Glu Val Gly Ile Asp Thr
165 170 175
Ala His Arg Ala Ser Arg Ala Gln Asn Asp Asn Glu Leu Arg Leu Val
180 185 190
Ser Leu His Gly Asp Phe Arg Tyr Asp Ala Leu Lys Asn Thr Ala Asp
195 200 205
Glu Leu Arg Glu Gln Asp Ala Ala Leu Arg Lys Glu Phe Leu His Glu
210 215 220
Leu Lys Asp Tyr Asp Leu Ile Val Ile Gly Tyr Ser Gly Arg Asp Glu
225 230 235 240
Ser Leu Met Arg Val Leu Ser Ala Ala Tyr Ala Asp Arg Ser Ser Cys
245 250 255
Arg Leu Tyr Trp Cys Gly Tyr Gly Ala Glu Pro Gly Thr Glu Val Gln
260 265 270
Arg Leu Ile Ser Ser Ile Asp Pro Ser Arg Glu Ser Ala Phe Tyr Ile
275 280 285
Asn Thr Lys Gly Phe Asp Asp Val Ile Ser Arg Leu Ala Val Arg Arg
290 295 300
Leu Ser Gly Lys Gln Leu Ala Phe Ala His Glu Leu Ile Glu Thr Met
305 310 315 320
Ala Pro Thr Val Gly Gln Arg Met Ala Phe Ala Val Pro Pro Leu Ser
325 330 335
Pro Ser Ala Leu Val Lys Gly Asn Ala Tyr Arg Leu Ser Tyr Pro Gly
340 345 350
Asn Ala Leu Lys Leu Asp Ile Glu Leu Pro Glu Leu Gly Ser Trp Arg
355 360 365
Glu Trp Leu Ala Glu Arg Met Pro Pro Thr Leu Gly Gln Ser Val Val
370 375 380
Phe Glu Asn Gly Ala Leu Cys Leu Ala Asp Thr Ala Val Ala Ser Arg
385 390 395 400
Val Phe Asp Glu Ala Leu Arg Arg Pro Pro Arg Arg Ile Glu Ile Ser
405 410 415
Asp Glu Asn Ile Val Thr Asp Gly Arg Ile Thr Ser Leu Phe Arg Arg
420 425 430
Ala Ile Val Lys Ala Ala Ala Lys Thr Leu Asn Val Arg Thr Asp Phe
435 440 445
Arg Arg Arg Ile Trp Glu Pro Ile His Tyr Gln Thr Arg Glu Leu Asp
450 455 460
Asn Val Arg Tyr Leu Ile His Arg Ala Leu Ser Met Asn Ile Val Gly
465 470 475 480
Ile Asp Gly Ile Pro His Val Val Leu Thr Pro Glu Ile Val Ala Thr
485 490 495
Met Glu Asp Gly Gly Val Ala Pro Phe Glu Pro Gln Lys Ala Leu Arg
500 505 510
Val Ala Ile Tyr Gly Phe Gln His Asn Asp Lys Phe Asp Gly Asp Leu
515 520 525
Ser Tyr Trp Thr Arg Gln Leu Val Glu Lys Ala Leu Asp Ala Asp Gly
530 535 540
Gly Gly Ala Phe Thr Ile Ser Lys Ile Pro Leu Tyr Ala Gly Leu Ala
545 550 555 560
Gln Lys Gly Lys Pro Pro Leu Pro Pro Thr Leu Ala Lys His Ala Lys
565 570 575
Gln Ser Gly Ile Ile Val Pro Asp Ala Pro Leu Val Phe Ser Ala Lys
580 585 590
Val Gly Thr Ser Glu Val Arg Asn Pro Asn Pro Leu His Gly Leu Val
595 600 605
Leu Asn Arg Pro Trp Asp His Ser Leu Thr Ala Thr Gly Leu Cys Pro
610 615 620
Ser Thr Glu Thr Ala Val Ile Cys Pro Ala Asp Ala Ser Thr Arg Phe
625 630 635 640
Glu Arg Phe Leu Arg Gly Leu Gln Glu Val Ala Arg Pro Glu Gln Ser
645 650 655
Glu Arg Asp Tyr Leu His Asp Phe Pro Gly Phe Pro Ala Ala Phe Gly
660 665 670
Leu Pro Leu Lys Ile Pro Val Arg Gly Asp Ser Thr Trp Met Thr Ile
675 680 685
Asp Asp Ser Val Ser Thr Asp Ala Leu Thr Gly Ala Lys Gln Leu Ala
690 695 700
His Arg Ile Cys Glu Gly Leu Asp His Leu Arg Arg Ala Arg Pro Ser
705 710 715 720
Asp Thr Val Val Ile Phe Val Pro Lys Arg Trp Glu Pro Phe Lys Val
725 730 735
Val Asp Thr Gln His Glu Arg Phe Asn Leu His Asp Tyr Ile Lys Ala
740 745 750
Tyr Ala Ala Arg His Ser Gln Ser Thr Gln Phe Val Arg Glu Glu Thr
755 760 765
Val Leu Asn Ser Tyr Thr Cys Arg Val Arg Trp Trp Leu Ser Leu Ala
770 775 780
Leu Tyr Val Lys Ala Met Arg Thr Pro Trp Arg Leu Asp Ala Leu Asp
785 790 795 800
Glu Asn Thr Ala Phe Val Gly Ile Gly Tyr Ser Leu Asp Ser Glu Ala
805 810 815
Glu Arg Gly Asn His Val Leu Leu Gly Cys Ser His Ile Tyr Ser Ala
820 825 830
Arg Gly Glu Gly Leu Gln Phe Arg Leu Gly Arg Ile Glu Asn Pro Val
835 840 845
Met Arg Gly Arg Asn Pro Phe Met Ser Glu Asp Asp Ala Arg Arg Thr
850 855 860
Gly Asp Thr Ile Arg Gln Leu Phe Tyr Asp Ser Lys Met His Leu Pro
865 870 875 880
Thr Arg Val Val Ile His Lys Arg Thr His Phe Thr Asp Glu Glu Arg
885 890 895
Arg Gly Leu Val Gln Gly Leu Asp Gly Val Lys Asn Ile Glu Leu Ile
900 905 910
Glu Ile Asn Val Glu Asp Ser Leu Arg Tyr Leu Ser Ser Lys Phe Lys
915 920 925
Asp Gly Lys Leu Asp Ile Asp Thr Phe Pro Val Tyr Arg Gly Thr Thr
930 935 940
Ile Val Glu Ser Asp Asp Thr Ala Leu Leu Trp Val His Gly Ala Thr
945 950 955 960
Pro Ser Ala Gln Asn Lys Tyr Trp Arg Tyr Tyr Gln Gly Lys Arg Arg
965 970 975
Ile Pro Ala Pro Leu Arg Ile Arg Arg Phe Leu Gly Gln Ser Asp Val
980 985 990
Val Gln Cys Ala Thr Glu Ile Leu Gly Leu Ser Lys Met Asn Trp Asn
995 1000 1005
Thr Leu Asp Tyr Tyr Ser Arg Met Pro Ala Thr Leu Asp Ser Ala
1010 1015 1020
Ser Ser Ile Ala Lys Phe Gly Thr Tyr Leu Asp Gly Phe Ser Ser
1025 1030 1035
Ala Pro Tyr Asp Tyr Arg Leu Leu Ile
1040 1045
<210> 33
<211> 1062
<212> PRT
<213> artificial sequence
<400> 33
His Asn Arg Ala Ala Leu Gln Thr Gly Ser Ser Val Arg Arg Met Gly
1 5 10 15
Val Asp Ala Leu Val Arg Ser Leu Ala Val Ser Gln Asp Arg Pro Leu
20 25 30
Met Leu Phe Leu Gly Ala Gly Ala Ser Met Thr Ser Gly Met Pro Ser
35 40 45
Ala Asn Gln Cys Ile Trp Glu Trp Lys Arg Asp Ile Phe Leu Ser Asn
50 55 60
Asn Pro Gly Ile Glu Glu Gln Phe Ser Glu Leu Ser Leu Pro Ser Val
65 70 75 80
Arg Asp Arg Ile Gln Thr Trp Leu Asp Arg Gln Arg Cys Tyr Pro Val
85 90 95
Ala Gly His Pro Asp Glu Tyr Gly Ala Tyr Ile Glu Ala Cys Phe Ser
100 105 110
Arg Ser Asp Asp Arg Arg Arg Tyr Phe Glu Arg Trp Val Lys Gln Ser
115 120 125
Thr Pro His Thr Gly Tyr Arg Leu Leu Ala Glu Leu Ala Ala Ser Gly
130 135 140
Leu Ile Gln Thr Val Trp Thr Thr Asn Phe Asp Gly Leu Ile Ala Arg
145 150 155 160
Ala Ala Ala Ala Thr Asn Leu Thr Pro Ile Glu Ile Gly Val Asp Ser
165 170 175
Gln Gln Arg Leu Tyr Arg Ala Pro Gly Lys Gly Glu Leu Ala Cys Val
180 185 190
Ser Met His Gly Asp Tyr Arg Tyr Asp Arg Leu Lys Asn Ser Ser Gly
195 200 205
Glu Leu Ala Gln Val Glu Val Gln Leu Arg Asp Ser Leu Ile Glu Ala
210 215 220
Leu Arg Thr His Thr Val Val Val Ala Gly Tyr Ser Gly Arg Asp Glu
225 230 235 240
Ser Val Met Gln Ala Phe His Gln Tyr Ala Ile Ser Gly Pro Val Arg
245 250 255
Thr Asp Leu Pro Leu Phe Trp Thr Gln Tyr Gly Glu Ala Pro Pro Leu
260 265 270
Asp Thr Val Asn Ala Leu Leu Ser Thr Asn His Gly Glu Pro Ser Arg
275 280 285
Phe Leu Val Pro Gly Val Ser Phe Asp Asp Leu Met Arg Arg Leu Ala
290 295 300
Leu Tyr Leu Ser Lys Gly Pro Ala Arg Asp Arg Val Asn Lys Ile Leu
305 310 315 320
Asp Glu His Ala Thr Thr Pro Val Asn Gln Leu Thr Ala Phe Gly Leu
325 330 335
Pro Pro Leu Pro Pro Thr Gly Leu Ile Lys Ser Asn Ala Ile Pro Leu
340 345 350
Thr Pro Pro Gln Glu Leu Leu Glu Phe Asp Leu Leu Gln Trp Pro Ala
355 360 365
Ser Gly Thr Val Trp Ala Thr Leu Arg Glu Leu Gly Asp Arg His Asn
370 375 380
Phe Val Ala Ala Pro Phe Arg Ser Lys Ile Tyr Ala Ile Ala Met Ala
385 390 395 400
Glu Ser Leu Arg Val Ala Phe Gly Glu Asn Leu Lys Gly Glu Ile Lys
405 410 415
Arg Val Pro Leu Asn Asp Asp Asp Leu Arg Tyr Glu Asp Gly Val Ile
420 425 430
Asn Gln Leu Val Arg Arg Ala Thr Val Leu Ala Leu Ser Ala Lys Ala
435 440 445
Asn Cys Pro Ser Asp Gly Glu Ser Leu Ile Trp Thr Ser Glu Lys Val
450 455 460
Glu Asp Leu Arg Leu Asp Arg Val Asp Trp Lys Val His Gln Ala Val
465 470 475 480
Leu Val Gln Ile Arg Pro Leu Gly Ser Glu Leu Ala Leu Val Leu Lys
485 490 495
Pro Thr Leu Tyr Val Thr Asp Arg Ser Gly Ala Ile Ala Pro Lys Asp
500 505 510
Thr Glu Arg Leu Val Lys Gln Arg Val Leu Gly Tyr Gln His Asn Lys
515 520 525
Glu Phe Asn Gly Ala Thr Glu Ala Trp Arg Arg Arg Leu Val Pro Gln
530 535 540
Arg Asp Phe Arg Val Arg Phe Pro Asp His Glu Asn Gly Ile Asp Leu
545 550 555 560
Thr Phe Ser Gly Arg Pro Leu Phe Ala Arg Ile Thr Asp Glu Arg Glu
565 570 575
Arg Thr Val Ser Leu Ser Ala Ala Gln Glu Ser Ala Ala Arg Gln Ala
580 585 590
Gly Leu Gln Leu Ala Glu Pro Arg Leu Lys Phe Ala Arg Lys Ser Ala
595 600 605
Ala Gly Leu Ala Phe Asp Thr His Pro Val Arg Gly Leu Ile Asn Asn
610 615 620
Arg Pro Phe Asp Ser Ser Leu Thr Thr Thr Gly Ile Ala Ser Ser Ile
625 630 635 640
Arg Val Gly Ile Ile Ala Pro Ala Arg Asp Ala Thr Arg Val His Gln
645 650 655
Tyr Leu Ser Gln Leu His Val Ala Ala Gln Pro Gly Lys Asp Ala Asp
660 665 670
Tyr Leu Pro Pro Phe Pro Gly Phe Ala Ser Ala Tyr Gln Cys Pro Ile
675 680 685
Glu Ile Pro Ser Val Gly Glu Gln Ser Phe Val Gln Leu Asp Glu Pro
690 695 700
Asp Ser Met Thr Pro Ser Ser Ala Arg Ala Leu Ala Gly Ala Ile Thr
705 710 715 720
Arg Ser Ile Ala Ser Leu Ser Ala Ser Gln Arg Pro Asp Val Thr Ile
725 730 735
Ile Tyr Val Pro Asp Arg Trp Ala Pro Leu Arg Asn Tyr Met Ile Asp
740 745 750
Asp Glu Glu Phe Asp Leu His Asp Phe Val Lys Ala Ala Ala Ile Pro
755 760 765
Lys Gly Cys Ala Thr Gln Phe Val Glu Glu Asp Thr Leu Arg Asn Thr
770 775 780
Gln Gln Gln Cys Arg Val Arg Trp Trp Leu Ser Leu Ala Leu Tyr Val
785 790 795 800
Lys Ser Met Arg Thr Pro Trp Thr Leu Glu Gly Leu Ser Glu Lys Ser
805 810 815
Ala Tyr Val Gly Leu Gly Phe Ser Val Lys Arg Lys Thr Thr Gln Asn
820 825 830
Ala Gly Ala His Val Val Leu Gly Cys Ser His Leu Tyr Ser Pro Asn
835 840 845
Gly Ile Gly Leu Gln Phe Arg Leu Ser Lys Ile Glu Asp Pro Ile Met
850 855 860
Arg Asn Lys Asn Pro Phe Met Ser Phe Asp Asp Ala Arg Arg Leu Gly
865 870 875 880
Glu Gly Ile Arg Glu Leu Phe Phe Ala Ala His Leu Arg Leu Pro Glu
885 890 895
Arg Val Val Ile His Lys Gln Thr Pro Phe Leu Arg Glu Glu Arg Ser
900 905 910
Gly Leu Gln Ala Gly Leu Glu Gly Val Ala Cys Val Glu Leu Leu Gln
915 920 925
Ile Phe Val Asp Asp Thr Leu Arg Tyr Val Ala Ser His Pro Thr Ser
930 935 940
Asp Gly Lys Phe Glu Ile Asp Asn Tyr Pro Ile Arg Arg Gly Thr Thr
945 950 955 960
Val Val Ile Asp Asp His Thr Ala Leu Leu Trp Val His Gly Ala Ser
965 970 975
Thr Ala Leu Asn Pro Gly Arg His Tyr Phe Gln Gly Lys Arg Arg Ile
980 985 990
Pro Ala Pro Leu Val Ile Arg Arg His Ala Gly Thr Thr Asp Leu Met
995 1000 1005
Thr Ile Ala Asp Glu Val Leu Gly Leu Ser Lys Met Asn Phe Asn
1010 1015 1020
Ser Phe Asp Leu Tyr Gly Gln Leu Pro Ala Thr Ile Glu Thr Ser
1025 1030 1035
Arg Arg Val Ala Arg Ile Gly Ala Leu Leu Asp Arg Phe Ser Asp
1040 1045 1050
His Ser Tyr Asp Tyr Arg Leu Phe Met
1055 1060
<210> 34
<211> 471
<212> PRT
<213> artificial sequence
<400> 34
Thr Pro Gln Asp Thr Pro Phe Thr Leu Arg His Leu Glu Glu Pro Glu
1 5 10 15
Ile Gln Phe Glu Gly Gly Thr Glu Thr Ser Pro Lys Arg Gly Leu Ile
20 25 30
Arg Tyr Gly Pro Arg Leu Tyr Glu Glu Gly His His Thr Ile Lys Leu
35 40 45
Gly Ile Ile Gly Asp Arg Asp Ser Ile Arg Arg Leu Thr Glu Leu Leu
50 55 60
His Asp Met Glu Val Gly Ile His Pro Gly Thr Ser Asp Asn Pro Trp
65 70 75 80
Gln Val Pro Tyr Pro Gly Leu Gly Lys Ser Ser Pro Leu Asn Leu Ser
85 90 95
Ile Asn Ala Lys Lys Gly Trp Arg Arg Gln Ile Arg Arg Arg Asp Ile
100 105 110
Gln Ser Val Thr Ser Lys Ser Thr Pro Arg Asp Arg Met Glu Arg Phe
115 120 125
Leu Lys Leu Val Gln Lys Asp Ile Glu Ile Ile Glu Arg Asp Ser Val
130 135 140
Gln Pro Asn Ala Ile Ile Val Cys Ile Pro Gln Glu Val Met Asp Ala
145 150 155 160
Cys Thr Pro Glu Asn Gln Asp His Ala Arg Ile Gln Ser Glu Gly Ser
165 170 175
Asp Leu Arg Asn Arg Ile Lys Leu Ile Gly Met Glu Ala Arg Ile Pro
180 185 190
Thr Gln Leu Ile Lys Pro Ser Thr Leu Ala Ile Arg Thr Asp Arg Gln
195 200 205
Arg Ala Ser Arg Ala Trp Asn Leu Thr Val Gly Leu Leu Tyr Lys Ser
210 215 220
Gln Arg Gly His Pro Trp Lys Thr Arg Gln Ile Glu Asp Gly His Cys
225 230 235 240
Tyr Ala Gly Leu Ser Phe Tyr Arg Glu Arg Asp Glu Gly Asp Asp Val
245 250 255
Ile Arg Ala Ala Leu Ala His Val Phe His Gly Arg Asp His Ile Ile
260 265 270
Leu Gln Ser Asp Pro Leu Pro Asp Ile Thr Glu Asp Glu Asn Gly Ser
275 280 285
Pro His Leu Ser Tyr Glu Ala Ala Arg Gln Val Gly Glu Gln Ile Leu
290 295 300
Glu Tyr Tyr Glu Ala Gln Lys Gly Thr Arg Pro Ser Arg Phe Val Leu
305 310 315 320
His Lys Pro Ser Val Phe Trp Glu Glu Glu Arg Glu Gly Leu Leu Asp
325 330 335
Ala Thr Asp Gly Val Arg Asp Leu Asp Leu Val Trp Val Arg Arg Arg
340 345 350
Pro Lys Val Arg Leu Phe Pro Pro Thr Asp Tyr Pro Ala Met Arg Gly
355 360 365
Thr Leu Leu Ser Val Pro Asp Asp Asp Val His Tyr Leu Tyr Thr Ser
370 375 380
Gly Tyr Val Pro Glu Glu Thr Thr Tyr Gln Gly Ser Gly Val Pro Ser
385 390 395 400
Pro Ile Glu Ile Arg Pro Asp Glu Ile Cys Glu Thr Pro Ser Leu Glu
405 410 415
Ile Cys Lys Glu Ile Leu Phe Phe Thr Lys Leu Asp Trp Asn Thr Ser
420 425 430
Asp Tyr Ala Ile Arg Met Pro Ala Thr Val Ser Val Ala Lys Arg Val
435 440 445
Gly Thr Ile Leu Ser Glu Val Asp Thr Glu Ser Ile Ser Glu Val Arg
450 455 460
Pro Gln Tyr Phe Tyr Tyr Met
465 470
<210> 35
<211> 483
<212> PRT
<213> artificial sequence
<400> 35
Lys Phe Glu Thr Lys Ile Phe Asp Glu Pro Leu Leu Glu Phe Gly Asn
1 5 10 15
Gln His Tyr His Pro Asp Pro Arg Leu Gly Leu Phe Glu Ala Gly Pro
20 25 30
Leu Gln Thr Pro Leu Gly Asp Val Ile Asn Ile Ala Val Val Gly Ser
35 40 45
Ala Lys Thr Val Lys Asp Ser Arg Asp Phe Leu Gln Ala Ala Ala Val
50 55 60
Gly Phe Ala Gly Lys Ser Glu Lys His Pro Asn Leu His Pro Pro Phe
65 70 75 80
Pro Gly Leu Gly Asn Gln Asn Pro Phe Arg Cys Arg Phe Glu Ile Pro
85 90 95
Asp Gly Ala Val Thr Ala Ile Pro Gln Ala Arg Ile Glu Arg Ile Arg
100 105 110
Lys Glu Pro His His Gly Lys Ala Val Glu Met Ala Val Asp Glu Ile
115 120 125
Ile Glu Gln Leu Gln Thr Ile Asp Glu Gly Ser Ser Arg Pro Asp Val
130 135 140
Ala Ile Ile Ala Leu Pro Val Glu Leu Ile Glu Arg Val Trp Asn Ala
145 150 155 160
Lys Val Asp Ser Asp Ala Thr Leu Glu Glu Glu Asp Ser Ser Gly Ser
165 170 175
Asp Ala Pro Asn Phe Arg Gly Met Leu Lys Ala Lys Ala Met His Phe
180 185 190
Arg Phe Pro Ile Gln Ile Val Trp Glu Asp Val Leu Asp Glu Arg Ala
195 200 205
Val Ile Pro Leu Lys Ile Lys Glu Ser Ser Ala Arg Gln Ile Gln Asp
210 215 220
Gln Ala Ser Arg Thr Trp Asn Leu Leu Thr Thr Leu Tyr Tyr Lys Gly
225 230 235 240
Ser Gly Arg Val Pro Trp Arg Arg Ala Pro Gln Glu Gly Glu Phe Ser
245 250 255
Ala Cys Tyr Ile Gly Val Ser Phe Tyr Arg Glu Ala Gly Gly Gln Gln
260 265 270
Leu Phe Thr Ser Ala Ala Gln Met Phe Asp Glu Arg Gly Arg Gly Phe
275 280 285
Ile Leu Lys Gly Lys Gly Ala Gln Thr Glu Ser Arg Gly Arg His Pro
290 295 300
Tyr Leu Thr Gln Asp Asp Ala Lys Thr Leu Ile Ala Asp Ala Leu Ala
305 310 315 320
Ala Tyr Lys Lys His His Met Asn Tyr Pro Ala Arg Val Ile Val Leu
325 330 335
Lys Thr Ser Arg Phe Arg Asp Glu Glu Ala Asp Gly Ile Phe Glu Ala
340 345 350
Leu Asp Glu Val Gly Thr Glu Leu Arg Asp Leu Val Trp Val Gln Glu
355 360 365
Ser Ser Phe Val Lys Val Phe Arg Asp Gly Asn Tyr Pro Val Met Arg
370 375 380
Gly Thr Phe Val Lys Leu Asp Gly Lys Gly Leu Leu Tyr Thr Asn Gly
385 390 395 400
Ser Ile Pro Tyr Tyr Gly Thr Tyr Pro Gly Met Tyr Asp Pro Lys Pro
405 410 415
Leu Leu Ile Cys Pro Tyr Lys Thr Ser Asp Ser Thr Val Ala Gln Ile
420 425 430
Ala Asn Glu Ile Phe Gly Leu Thr Lys Ile Asn Trp Asn Ser Thr Gln
435 440 445
Met Asn Gln Lys Leu Pro Ile Pro Ile Arg Ala Ala Arg Lys Val Gly
450 455 460
Glu Val Leu Lys Tyr Ile Thr Asp Glu Lys Val Ser Ser Asp Tyr Arg
465 470 475 480
Arg Tyr Ile
<210> 36
<211> 625
<212> PRT
<213> artificial sequence
<400> 36
Arg Asn Ile Leu Leu Asn Phe Leu Lys Phe Glu Asn Gln Asp Phe Gly
1 5 10 15
Thr Thr Val Phe Arg Lys Glu Ala Glu Ala Gly Val Phe Lys Asp Gly
20 25 30
Phe Ser Tyr Tyr Asp Phe Glu Val Asp Gly Arg Asn Val Lys Tyr Glu
35 40 45
Ile Ser Asp Thr Ala Leu Glu Gly Tyr Thr Ser Phe Thr Leu Pro Ser
50 55 60
Tyr Leu Asn Val Gly Leu Val Ser Lys Lys Leu Tyr Glu Lys Ile Ile
65 70 75 80
Asp Ala Ser Asn Gln Val Asn Gly Arg Phe Ile Leu His Pro Glu Lys
85 90 95
Glu Tyr Asn Arg Arg Ile His Phe Glu Ile Glu Pro His Pro Lys Gly
100 105 110
Arg Lys Cys Val Trp Val Glu Pro Tyr Phe Leu Lys Ser Lys Gln Val
115 120 125
Trp Gly Leu Leu Ile Gly Phe Gln Phe Ile Val Ser Gln Asn Val Leu
130 135 140
Ser Gly Gly Tyr Lys Val Asp Arg Asp Ile Gln Ile Ala Ser Gly Ser
145 150 155 160
Leu Asn Ala Arg Gly Leu Ser Asn Leu Asp Phe Tyr Leu Phe Lys Tyr
165 170 175
Asn His Ile Thr Thr Phe Ile Lys Asn Ile Leu Pro Gly Ile Asn Leu
180 185 190
Asn Leu Asn Asn Ala Ile Asn Ser Ser Leu Phe Pro Val Glu Ser Tyr
195 200 205
Leu Leu Asp Ala Lys Gln Tyr Met Phe Lys Asp Asn Arg Ile Asp Asn
210 215 220
Ser Ser Tyr Phe Gly Leu Ser Lys Tyr Ala Pro Leu Gln Pro Val Ser
225 230 235 240
Lys Glu Thr Thr Phe Tyr Phe Ile Tyr Arg Lys Ser Asp Arg Gly Ile
245 250 255
Ala Val Asn Leu Leu Lys Gly Leu Arg Gly Glu Ser His Pro Asn Thr
260 265 270
Phe Ser Gly Ile Gln Lys Phe Phe Lys Ile Pro Phe Thr Asn Asp His
275 280 285
Ile Lys Gly Phe Ala Leu Asp Asp Tyr Asn Glu Pro Asn Ile Ser Lys
290 295 300
Val Val Glu Asp Ile Lys Ala Glu Val Asn Asn Val Leu Pro Val Ile
305 310 315 320
Ile Thr Asn Ser Lys Lys Glu Glu Ser Asp Asp Lys Leu Tyr Phe Ser
325 330 335
Leu Lys His Arg Phe Thr Asn Glu Gly Ile Pro Cys Gln Val Val Thr
340 345 350
Lys Asp Leu Ile Ile Asn Asp Asn Ala Leu Lys Phe Ser Leu Gly Asn
355 360 365
Ile Ala Leu Gln Met Phe Ala Lys Ala Gly Gly Ile Pro Trp Lys Met
370 375 380
Lys Pro Ala Thr Thr Glu Tyr Leu Ile Ile Gly Ile Gly Gln Ser Tyr
385 390 395 400
Asn Ile Glu Ile Thr Glu Asp Gly Asn Lys Val Glu Lys Asn Ile Thr
405 410 415
Tyr Ser Val Leu Thr Asp Ser Ser Gly Ile Phe Lys Asp Leu Gln Val
420 425 430
Leu Ser Glu Gly Val Ala Thr Asp Asp Ser Tyr Tyr Thr Gln Leu Val
435 440 445
Asn Asn Ile Ala Gly Ile Ile Asn Asn Gly Lys Tyr Lys Lys Ile Ala
450 455 460
Val His Thr Pro Phe Arg Leu Ser Lys Asp Lys Val Leu Asp Lys Val
465 470 475 480
Val Lys Leu Ile Asp His Asn Ile Glu Leu Ser Val Leu Val Ile Asn
485 490 495
Asp Lys Thr Asp Phe Phe Gly Phe Asp Ala Ser Asn Asn Gly Leu Val
500 505 510
Pro Phe Glu Ser Thr Phe Leu Lys Leu Ser Ser Gln Glu Tyr Leu Val
515 520 525
Trp Phe Glu Gly Ile Gln Pro Ser Asn Pro Lys Ile Thr Lys Arg Phe
530 535 540
Gly Asn Pro Leu Ser Ile Lys Phe Trp Tyr Thr Asn Asn Pro Gln Phe
545 550 555 560
Phe Gln Asp Ile Asp Tyr Lys Glu Ser Leu Leu Gln Asp Cys Ile Asn
565 570 575
Leu Ser Gly Ala Asn Trp Arg Gly Phe Lys Ala Lys Gln Leu Pro Val
580 585 590
Ser Val Phe Tyr Cys Gln Arg Ile Ser Glu Phe Ile Gly Lys Phe Arg
595 600 605
Gln Tyr Glu Leu Ser His Ile Asp Ile Asn Asn Leu Lys Pro Trp Phe
610 615 620
Leu
625
<210> 37
<211> 490
<212> PRT
<213> artificial sequence
<400> 37
Ser Asp Phe Lys Thr Lys Ile Phe Pro Glu Pro Glu Leu Glu Phe Gly
1 5 10 15
Asp Gln His His His Pro Asp Pro Arg Leu Gly Leu Leu Gln Ala Gly
20 25 30
Pro Leu Gln Thr Asn Leu Gly Asp Thr Ile Lys Val Gly Val Val Gly
35 40 45
Ser Ala Leu Thr Val Glu Lys Ser Gly Glu Phe Leu Asn Ala Ile Glu
50 55 60
Asp Gly Phe Glu Gly Lys Thr Glu Lys His Pro Asn Leu His Pro Asp
65 70 75 80
Phe Pro Gly Leu Arg Asn Gln Asn Pro Tyr Arg Cys Arg Phe Glu Met
85 90 95
Val Ala Ala Glu Asp Gly Val Leu Thr Lys Gly Gln Ile Glu Lys Ile
100 105 110
Ala Lys Glu Pro Ser Asp Ala Arg Ala Val Glu Ile Ala Val Asp Ala
115 120 125
Val Met Ala Gln Leu Glu Lys Leu Glu Ala His His Glu Arg Pro Asp
130 135 140
Val Val Met Val Ser Leu Pro Val Lys Leu Ile Glu Arg Val Trp Arg
145 150 155 160
Asn Glu Arg Ala Arg Asp Asp Glu Gly Ile Glu Gly Glu Ala Ala Asp
165 170 175
Ala Lys Ala Gly Arg Glu Thr Ser Pro Asn Phe Arg Gly Leu Leu Lys
180 185 190
Ala Arg Ala Met Asp Leu Arg Phe Ser Ile Gln Ile Val Trp Glu Asp
195 200 205
Val Ile Asn Pro Asp Ala Lys Ile Pro Arg Lys Ile Lys Glu Asn Ser
210 215 220
Asp Arg Gln Thr Gln Asp Arg Ala Asp Leu Ala Trp Asn Leu Met Thr
225 230 235 240
Thr Leu Tyr Tyr Lys Gly Ser Gly Lys Val Pro Trp Arg Arg Leu Pro
245 250 255
Glu Glu Gly Glu Phe Thr Ala Cys Tyr Ile Gly Ile Ser Phe Phe Lys
260 265 270
Asp Ala Glu Thr Asp Glu Ile Trp Thr Ser Ala Ala Gln Met Phe Asp
275 280 285
Glu Arg Gly Arg Gly Phe Ile Leu Arg Gly Gly Pro Ala Gln Ser Glu
290 295 300
Ser Arg Gly Arg His Pro Phe Leu Thr Ile Asp Glu Ala His Lys Leu
305 310 315 320
Thr Glu Ser Ala Leu Ala Ala Tyr Lys Ser Val His Arg Thr Met Pro
325 330 335
Ala Arg Val Ile Val Met Lys Thr Ser Arg Phe Arg Glu Asp Glu Ala
340 345 350
Glu Gly Val Gly Lys Ala Leu Asp Glu Ala Gly Val Glu Leu Arg Asp
355 360 365
Leu Val Trp Ile His Glu Ser Tyr Ser Val Lys Val Leu Arg Asp Gly
370 375 380
Asp Phe Pro Val Leu Arg Gly Thr Phe Val Glu Leu Asp Gly Asn Gly
385 390 395 400
Leu Leu Tyr Thr Asn Gly Ser Ile Pro Tyr Tyr Gly Thr Tyr Pro Gly
405 410 415
Leu Tyr Val Pro Asn Pro Leu Leu Leu Cys Pro His Pro Gln Ser Glu
420 425 430
Ser Thr Ile Glu Gln Ile Ala Lys Glu Val Phe Ser Leu Thr Lys Val
435 440 445
Asn Trp Asn Ser Thr Gln Met Asn Gln Arg Leu Pro Ile Pro Ile Arg
450 455 460
Ala Ala Arg Lys Val Gly Asp Val Leu Lys Tyr Val Pro Ser Gly Gln
465 470 475 480
Lys Val Ser Ser Asp Tyr Arg Lys Tyr Ile
485 490
<210> 38
<211> 638
<212> PRT
<213> artificial sequence
<400> 38
Tyr Leu Asn Leu Tyr Lys Ile Asp Ile Pro Lys Lys Ile Lys Arg Leu
1 5 10 15
Tyr Phe Tyr Asn Pro Asp Met Glu Pro Lys Leu Phe Ala Arg Asn Leu
20 25 30
Ser Arg Val Asn Asn Phe Lys Phe Gln Asp Ser Asn Asp Leu Val Trp
35 40 45
Ile Glu Ile Pro Asp Ile Asp Phe Gln Ile Thr Pro Lys Asn Val Phe
50 55 60
Gln Tyr Lys Val Glu Lys Glu Glu Ile Ile Lys Glu Glu Glu Asp Lys
65 70 75 80
Lys Leu Phe Val Lys Thr Leu Tyr Lys Tyr Ile Lys Lys Leu Phe Leu
85 90 95
Asp Asn Asp Phe Tyr Phe Lys Lys Gly Asn Asn Phe Ile Ser Asn Ser
100 105 110
Glu Val Phe Ser Leu Asp Ser Asn Glu Asn Val Asn Ala His Leu Thr
115 120 125
Tyr Lys Ile Lys Ile His Asn Ile Ser Asn Glu Tyr Tyr Leu Ser Ile
130 135 140
Leu Pro Lys Phe Thr Phe Leu Ser Lys Glu Pro Ala Leu Glu Ser Ala
145 150 155 160
Ile Lys Ser Gly Tyr Leu Tyr Asn Ile Lys Ser Gly Lys Ser Phe Pro
165 170 175
Tyr Ile Ser Gly Leu Asp Gly Ile Leu Lys Ile Asp Ile Gly Asn Asn
180 185 190
Gln Ile Val Glu Val Ala Tyr Pro Glu Asn Tyr Leu Phe Asn Phe Thr
195 200 205
Thr Arg Asp Ala Glu Lys Tyr Gly Phe Ser Lys Glu Val His Glu Ile
210 215 220
Tyr Lys Asn Lys Val Phe Glu Gly Phe Lys Lys Ile Pro Lys Thr Leu
225 230 235 240
Gly Phe Leu Asn Lys Ile Thr Asn Leu Asn Glu Asn Tyr Gln Leu Lys
245 250 255
Asp Gly Tyr Lys Ile Phe Ile Asn Val Ile Tyr Lys Phe Lys Asn Gly
260 265 270
Glu Ser Arg Tyr Ala Lys Asp Val Phe Lys Tyr Ser Phe Tyr Lys Asn
275 280 285
Glu Gln Pro Leu Lys Ala Ile Phe Phe Phe Ser Ser Lys Lys Gln Phe
290 295 300
Phe Glu Val Gln Lys Ser Leu Lys Glu Leu Phe His Asn Lys His Ser
305 310 315 320
Val Phe Tyr Arg Ala Ala Ala Glu Leu Gly Phe Ser Lys Val Glu Phe
325 330 335
Leu Arg Asp Ser Lys Thr Lys Ser Ser Ala Phe Leu Tyr Asn Pro Glu
340 345 350
Glu Phe Thr Val Lys Asn Thr Glu Phe Ile Asn Gln Ile Glu Asp Asn
355 360 365
Val Met Ala Ile Val Leu Leu Asp Lys Tyr Ile Gly Asn Ile Asp Pro
370 375 380
Leu Val Arg Asn Phe Pro Asp Asn Leu Ile Leu Gln Pro Ile Leu Lys
385 390 395 400
Glu Lys Leu Glu Asp Ile Lys Pro Phe Ile Ile Lys Ser Tyr Val Tyr
405 410 415
Lys Met Gly Asn Phe Ile Pro Glu Cys Lys Pro Phe Ile Leu Lys Lys
420 425 430
Met Glu Asp Lys Glu Lys Asn Leu Tyr Ile Gly Ile Asp Leu Ser His
435 440 445
Asp Thr Tyr Ala Arg Lys Thr Asn Leu Cys Ile Ala Ala Val Asp Asn
450 455 460
Thr Gly Asp Ile Leu Tyr Ile Gly Lys His Lys Asn Leu Glu Leu Asn
465 470 475 480
Glu Lys Met Asn Leu Asp Ile Leu Glu Lys Glu Tyr Ile Lys Ala Phe
485 490 495
Glu Lys Tyr Ile Glu Lys Phe Asn Val Ser Pro Glu Asn Val Phe Ile
500 505 510
Leu Arg Asp Gly Arg Phe Ile Glu Asp Ile Glu Ile Ile Lys Asn Phe
515 520 525
Ile Ser Tyr Asn Asp Thr Lys Tyr Thr Leu Val Glu Val Asn Lys Asn
530 535 540
Thr Asn Ile Asn Ser Tyr Asp Asp Leu Lys Glu Trp Ile Ile Lys Leu
545 550 555 560
Asp Glu Asn Thr Tyr Ile Tyr Tyr Pro Lys Thr Phe Leu Asn Gln Lys
565 570 575
Gly Val Glu Val Lys Ile Leu Glu Asn Asn Thr Asp Tyr Thr Ile Glu
580 585 590
Glu Ile Ile Glu Gln Ile Tyr Leu Leu Thr Arg Val Ala His Ser Thr
595 600 605
Pro Tyr Thr Asn Tyr Lys Leu Pro Tyr Pro Leu His Ile Ala Asn Lys
610 615 620
Val Ala Leu Thr Asp Tyr Glu Trp Lys Leu Tyr Ile Pro Tyr
625 630 635
<210> 39
<211> 737
<212> PRT
<213> artificial sequence
<400> 39
Met Glu Ala Tyr Ile Thr Glu Met Val Ser Arg Glu Arg Ala Asn Glu
1 5 10 15
Leu Glu Val Tyr Val Tyr Val Phe Pro Arg Lys Gln Ser Asp Asn Asn
20 25 30
Tyr Glu Gly Val Tyr His Ile Met Arg Ala Trp Gln Arg Ala Asn Asp
35 40 45
Leu Pro Leu Ala Tyr Asn Gln His Thr Ile Met Ala Phe Ser Pro Val
50 55 60
Arg His Met Cys Gly Tyr Thr Pro Met Glu Thr Gln Lys Arg His Ile
65 70 75 80
Asn Ile Asp Ser Pro Phe Glu Arg Ala Leu Leu Glu Arg Leu Ile Lys
85 90 95
Asn Ser Leu Ile Phe Thr Ala Glu Arg His Leu His Ala Lys Arg Val
100 105 110
Gly His Ala Leu Arg Leu Asn Gln Val Gln Gln Ile Arg Gln Val Ile
115 120 125
Ile Tyr Glu Ala Ile Glu Leu Tyr Val Asn Ile Ile Glu Asn Arg Ile
130 135 140
Ser Ile Gly Phe His Leu Thr His Gln Phe Glu Tyr Val Tyr Thr Leu
145 150 155 160
Gln Ser Met Ile Glu Gln Gly Lys Thr Ile Arg Pro Gly Met Arg Val
165 170 175
Val His Ser Asn Gly Arg Gln His Tyr Thr Tyr Thr Val Glu Asn Val
180 185 190
Ala Thr Tyr Gly Val Thr Asp Arg Cys Pro Leu Leu Gln Thr Ser Ile
195 200 205
Tyr Gln Tyr Tyr Val Glu Lys Gly Ala Gln His Ile Leu Arg Thr Phe
210 215 220
Thr Arg Ser Thr Arg Val Ile His Val Arg Thr Lys Glu Gln Arg Leu
225 230 235 240
Ser Tyr Ala Ala Thr Leu Leu Lys Pro Leu Cys Thr Phe Glu Thr Met
245 250 255
Gln Pro Gln Asp Val Leu Asn Val Ser Lys Cys Ile Lys Leu Ser Ala
260 265 270
Ser Lys Arg Met Lys Cys Thr Tyr Arg Trp Ile Gln Gln Leu Arg Ala
275 280 285
Gln Tyr Arg His Leu Thr Phe Ala Pro Asn Pro Phe Thr Ile Ala Gln
290 295 300
Asn Gly Tyr Lys Leu Asp Gln Leu Ser Thr Pro Lys Val His Phe His
305 310 315 320
Arg Asp Tyr Ala Thr Val Val Ser Gly Met Lys Thr Gly Lys Leu Tyr
325 330 335
Lys Gly Gly Asn Ile Lys Ile Ser Val Leu Phe Asp Glu Asp Phe Tyr
340 345 350
Leu Lys His His Ile Thr Lys Lys Asp Ile Tyr Gln Phe Ile Ala Val
355 360 365
Leu Gln Lys Ile Ala Ile Ala Gln Gly Val Asn Met Thr Ile Ser Thr
370 375 380
Ser Thr Lys Ser Ile Thr Gly Lys Phe Thr Asp Asp Phe Phe His His
385 390 395 400
Phe Thr Glu Glu Val Glu Ala Leu Gln Pro Ile Phe Ala Gln Thr Thr
405 410 415
Val Leu Ala Phe Ile Thr Ser Thr His Leu Ser Asn Lys Lys Thr Arg
420 425 430
Ser Tyr Gln Leu Leu Lys Gln Tyr Phe Gly Gly Lys Trp Asp Ile Ala
435 440 445
Ser Gln Val Ile Thr Glu Lys Thr Ile Glu Ala Phe Gln Lys Ile Leu
450 455 460
His Lys His Gly Leu Lys Asn Phe Tyr Pro Asn Asp Glu Gln His Cys
465 470 475 480
Leu Arg Val Ile Asp Val Leu Lys Asn Glu Ser Phe Tyr Tyr Thr Val
485 490 495
Met Asn Ile Leu Leu Gly Val Tyr Val Lys Ser Gly Ile Gln Pro Trp
500 505 510
Ile Leu Ala Asn Thr Thr His Ser Asp Cys Phe Ile Gly Ile Asp Val
515 520 525
Ser His Glu Asn Gly Asn Ser Ala Ala Gly Met Met Asn Val Ile Gly
530 535 540
Ser Gln Gly His Leu Ile Gln Gln Ala Pro Leu Asn Gly Ile Leu Ala
545 550 555 560
Gly Glu Lys Ile Asp Asp Thr Leu Leu Ala Asn Leu Leu Lys Gln Met
565 570 575
Ile Lys Ala Tyr His Thr Gln Phe Gln Arg Phe Pro Lys His Ile Thr
580 585 590
Ile His Arg Asp Gly Phe Trp Arg Glu His Thr Ala Leu Val Glu Lys
595 600 605
Ile Met Ser His Tyr Glu Ile Thr Tyr Asp Ile Val Glu Ile Ile Lys
610 615 620
Lys Pro Asn Arg Arg Met Ala Phe Phe Asn Ser Val Asp Asn Thr Phe
625 630 635 640
Ser Thr Arg Gln Gly Thr Val Tyr Gln Arg Gly Asn Glu Ala Phe Leu
645 650 655
Cys Ala Thr Asn Pro Gln Gln Lys Val Gly Met Ala Gln Pro Ile Lys
660 665 670
Ile His Gln Val Thr Lys Thr Leu Pro Phe Ser His Ile Ile Glu Asp
675 680 685
Val Tyr Asn Leu Ser Phe Leu His Ile His Ala Met Asn Lys Met Arg
690 695 700
Leu Pro Ala Thr Ile His Tyr Ala Asp Leu Ser Ala Thr Ala Tyr Gln
705 710 715 720
Arg Gly Gln Val Met Pro Arg Ser Gly Asn Gln Thr Asn Leu Pro Phe
725 730 735
Val
<210> 40
<211> 741
<212> PRT
<213> artificial sequence
<400> 40
Asp Leu Lys Met Glu Val Phe Ala Ser Val Asp Thr Val Lys Pro Val
1 5 10 15
Glu Phe His Val Tyr Glu Leu His Ala Gln Lys Ile Gly Asn Thr Tyr
20 25 30
Ser Ile Ile Arg Gly Ala Ala Trp Lys Leu Arg Asn Trp Asn Gln Ala
35 40 45
Gly Val Phe Glu Asp Gly Asn Lys Ile Tyr Ala Thr Glu Lys Leu Gln
50 55 60
Glu Lys Ile Pro Asn Ala Asp Phe Thr Val Glu Tyr Glu Gly Ser Arg
65 70 75 80
Glu Leu Pro Val Leu Glu Asn Arg Arg Ile Tyr Gln Glu Leu Ile Lys
85 90 95
Tyr Trp Ile Thr Gln Lys Leu Ser Gln Ile Leu Ile Phe Gly Lys Tyr
100 105 110
Arg Lys Tyr Ser Cys Lys Ser Asn Val Thr Ser Lys Trp Ile Met Thr
115 120 125
Asn Gln Gly Phe Glu Thr Phe Ser Ser Gly Asn Arg Glu Ile Ser Leu
130 135 140
Glu Arg Lys Tyr Asn Phe Trp Val Thr Ile Met Asp Asp Glu Lys Ala
145 150 155 160
Tyr Leu Arg Ile Asp Thr Ser Ser Leu Phe Ser Ser Asn Gln Thr Val
165 170 175
Ala Asp Tyr Leu Glu Lys Gly Leu Asn Leu Ile Gly Gln Glu Val Lys
180 185 190
Asn Asp Trp Ala Lys Asn Asn Gln Thr Gly Ile Leu Thr Glu Ile Cys
195 200 205
Asp Leu Thr Val Thr Asp Lys Leu Asp Phe Ala Asp Ser Leu Lys Ala
210 215 220
Tyr Tyr Ile Gln Arg Asn Glu Ala Tyr Arg Val Glu Asn Ile Ser Asp
225 230 235 240
Asp Thr Arg Ile Val Lys Val Ala Leu Gln Thr Gly Ile Glu Leu Pro
245 250 255
Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr Arg Glu Thr Val Ser
260 265 270
Arg Met Asp Ala Ala Phe Ser Met Arg Thr Glu Ser Leu Val Lys Arg
275 280 285
Asn Met Lys Thr Arg Val Leu Leu Asp Gln Asp Phe Ile Gln Asp Ile
290 295 300
Gly Thr Ile Glu Pro Leu Asp Gly Met Lys Phe Glu Thr Asp Pro Cys
305 310 315 320
Thr Val Glu Lys Ile Gly Tyr Lys Lys Gly Lys Val Lys Glu Pro Leu
325 330 335
Leu Val Cys Gly Lys Asp Lys Ala Leu Lys Cys Gly Glu Glu Phe Lys
340 345 350
Val Phe Asn Tyr Gly Phe Tyr Arg Lys Thr Glu Lys Glu Ile Lys Ile
355 360 365
Gly Tyr Leu Tyr Pro Arg Asn Ser Tyr Asp Leu Met Lys Ala Val Val
370 375 380
Asn Gly Ile Tyr Thr Phe Ala Lys Leu Gly Lys Tyr His Gly Glu Lys
385 390 395 400
Asp Leu Tyr Thr Met Ala Gly Leu Leu Asp Leu Asp Val Lys Ala Met
405 410 415
Val Arg Glu Glu Tyr Glu Leu Gly Asp Ile Thr Asp Tyr Lys Arg Ala
420 425 430
Ala Asn Lys Leu Gln Lys Ile Glu Gly Ile Asp Leu Val Ile Ala Leu
435 440 445
Val Pro Asp Gly Met Glu Glu Asp Gly Pro Tyr Asn Pro Phe Lys Thr
450 455 460
Ile Trp Ala Lys Ala Asn Ile Pro Ser Gln Met Ile Ser Met Lys Thr
465 470 475 480
Ala Lys Leu Phe Ala Glu Glu Ala Lys Glu Gly Asn Lys Ala Lys Asn
485 490 495
Asn Ser Arg Tyr Tyr Leu His Asn Ile Ile Leu Gly Ile Leu Gly Lys
500 505 510
Thr Gly Gly Ile Pro Trp Val Val Lys Asp Met Pro Gly Asn Val Asp
515 520 525
Cys Phe Val Gly Leu Asp Val Ala Thr Ile Ala Lys Gly Ile His Tyr
530 535 540
Pro Ala Cys Ser Val Val Phe Asp Lys Tyr Gly Arg Leu Leu Gly Phe
545 550 555 560
Tyr Lys Pro Ala Ala Pro Gln Gln Gly Glu Lys Ile Thr Thr Arg Ile
565 570 575
Leu Gln Asp Ile Phe Asp Gln Val Ile Phe Ala Tyr Glu Asp Arg Phe
580 585 590
Gly Glu Met Pro Lys Asn Ile Val Ile His Arg Asp Gly Phe Ser Asn
595 600 605
Glu Asp Asp Glu Trp Tyr Lys Asn Tyr Phe Ala Ala Lys Gly Ile Met
610 615 620
Tyr Asn Ile Ile Glu Val Arg Lys Asn Ile Ser Ser Lys Leu Ile Phe
625 630 635 640
Trp Gln Asn Gly Gln Ile Glu Asn Pro Pro Met Gly Tyr Cys Val Tyr
645 650 655
Asn Ala Asp Lys Gly Tyr Leu Val Thr Thr Asn Met Lys Asn Lys Lys
660 665 670
Gly Ser Pro Asn Pro Ile Leu Ile Glu Lys Lys Cys Gly Asn Leu Ser
675 680 685
Met Ala Asp Ile Leu Thr Gln Val Leu Tyr Leu Ser Gln Leu His Val
690 695 700
Gly Ser Thr Gln Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp
705 710 715 720
Lys Ile Cys Lys Asn Arg Glu Phe Val Pro Glu Gly Lys Met Asp Asp
725 730 735
Arg Leu Phe Phe Leu
740
<210> 41
<211> 753
<212> PRT
<213> artificial sequence
<400> 41
Leu Glu Ile Phe Lys Ser Asn Ile Gln Leu Lys Glu Gln Lys Phe His
1 5 10 15
Glu Tyr Thr Leu Ser Gly Val Gly Ser Val Asp Asn Phe Tyr Gln Leu
20 25 30
Val Gly Gln Ala Gln Tyr Ala Leu Ser Ser Gln Asn Lys Phe Glu Phe
35 40 45
Val Ser Arg Met Gly Asp Met Tyr Leu Tyr Ser Leu Lys Lys Leu Glu
50 55 60
Asn Met Pro Glu Ile Lys Gly Val Lys Ile Glu Tyr Thr Gly Cys Lys
65 70 75 80
Asn Leu Asp Ile Lys Asn His Lys Glu Val Tyr Ser Asn Leu Ile Val
85 90 95
Tyr Tyr Ile Asn Lys Ile Leu Lys Tyr Lys Lys Ile Tyr Asp Lys Thr
100 105 110
Glu Glu Lys Glu Val Glu Lys Tyr Lys Ile Lys Phe Arg Lys Ser Ile
115 120 125
Phe Asn Pro Val Ile Leu Gln Lys Glu Glu Asn Lys Lys Ile Tyr Thr
130 135 140
Ser Ile Val Asn Arg Asp Gly Ile Arg Val Tyr Arg Val Phe Asn Ile
145 150 155 160
Met Pro Tyr Ile Asp Asp His Gly Tyr Ala Tyr Leu Arg Cys Asp Ile
165 170 175
Asn His Ile Phe Glu Ser Asp Lys Thr Ile Tyr Asp Met Met Lys Glu
180 185 190
Asn Lys Asn Val Ile Gly Leu Lys Val Asp Tyr Leu Trp Thr Asn Asn
195 200 205
Thr Asn Ser Thr Gly Ile Ile Glu Asp Val Ile Asp Lys Thr Ile Ser
210 215 220
Asp Lys Leu Val Glu Leu Lys Gly Gln Ser Leu Ile Asp Tyr Phe Ile
225 230 235 240
Asn Asn Lys Gln Glu Tyr Arg Val Asn Lys Phe Thr Glu Glu Asp Lys
245 250 255
Lys Ala Asn Val Ile Lys Val Lys Gly His Lys Asn Thr Phe Tyr Phe
260 265 270
Ile Pro His Ser Leu Lys Gln Val Ile Asp Arg Glu Ser Leu Lys Ser
275 280 285
Ile Asp Ser Lys Phe Ser Ser Asp Ile Glu Lys Tyr Ile Lys Met Asp
290 295 300
Met Asn Tyr Arg Met Arg Ser Leu Ser Asp Phe Leu Asp Asp Ile Gly
305 310 315 320
Glu Ile Lys Glu Leu Gly Asn Leu Arg Phe Asp Phe Asn Leu Asn Ser
325 330 335
Ile Asn Glu Leu Gly Phe Lys Gln Arg Lys Ile Asp Lys Pro Tyr Phe
340 345 350
Leu Val Ser Asn Gly Lys Val Ile Lys Asn Lys Thr Gly Val Phe Tyr
355 360 365
Lys Gly Tyr Tyr Leu Lys Pro Asn Asn Lys Ile Arg Val Ala Ile Met
370 375 380
Cys Pro Glu Gly Tyr Val Glu Glu Ser Lys Asn Ala Leu Ser Lys Ile
385 390 395 400
Leu Ser Phe Asn Lys Asn Gly Tyr Ile Val Ser Asn Asp Lys Thr Glu
405 410 415
Gln Lys Asn Phe Ala Ile Lys Ser Leu Leu Asp Leu Glu Tyr Thr Gly
420 425 430
Ile Phe Tyr Lys Tyr Lys Leu Gly Asp Ile Thr Glu Tyr Lys Arg Ile
435 440 445
Ala Gly Asn Leu Ile Lys Asn Glu Lys Glu Phe Asp Leu Val Leu Cys
450 455 460
Val Ile Pro Asn Lys Ser Asp Glu Ser Asn Pro Tyr Ser Glu Phe Lys
465 470 475 480
Lys Ile Trp Ala Lys His Asn Ile Pro Ser Gln Met Ile Cys Ile Asp
485 490 495
Ser Leu Lys Ile Ile Asn Asn Cys Lys Asp Leu Asn Asn Tyr Asn Gly
500 505 510
Ile Tyr Tyr Ile Tyr Glu Ile Ser Leu Gly Met Leu Ala Lys Ser Gly
515 520 525
Gly Val Pro Trp Gly Leu Lys Glu Ile Asn Ser Asp Val Asp Cys Phe
530 535 540
Val Gly Leu Asp Val Gly Asn Pro Tyr Lys Gly Ile Arg Tyr Pro Ser
545 550 555 560
Ser Ser Val Val Phe Asp Lys Asn Gly Thr Leu Ile Asn Tyr Phe Lys
565 570 575
Pro Glu Ile Pro Gln Thr Gly Glu Ile Ile Val Glu Gly Ile Leu Gln
580 585 590
Glu Ile Phe Asp Glu Ile Ile Leu Ser Tyr Glu Arg Lys Phe Asn Gln
595 600 605
Lys Pro Lys His Ile Val Ile His Arg Asp Gly Phe Ala Arg Glu Asn
610 615 620
Ile Asn Trp Tyr Ile Asn Tyr Phe Ser Gln Lys Asn Ile Lys Phe Asp
625 630 635 640
Ile Val Glu Val Lys Lys Gln Gly Ala Val Lys Phe Ala Ile Lys Asp
645 650 655
Lys Asp Ile Phe Lys Asn Pro Glu Ala Gly Tyr Tyr Leu Thr Asn Gly
660 665 670
Lys Tyr Ala Tyr Leu Val Thr Asn Asp Ile Lys Ile Gly Ser Pro Arg
675 680 685
Pro Leu Lys Ile Glu Lys Val Tyr Gly Asp Thr Ser Leu Asp Asp Ile
690 695 700
Val Lys Gln Ile Phe Tyr Leu Ser Glu Leu His Val Gly Ser Phe Lys
705 710 715 720
Lys Thr Arg Leu Pro Ile Thr Thr Glu Tyr Ala Asp Arg Ile Ser Lys
725 730 735
Asn Ile Met Tyr Ile Pro Ser Gly Cys Leu Ser Lys Lys Leu Phe Phe
740 745 750
Leu
<210> 42
<211> 753
<212> PRT
<213> artificial sequence
<400> 42
Leu Glu Ile Phe Lys Ser Asn Ile Gln Leu Lys Glu Gln Lys Phe His
1 5 10 15
Glu Tyr Thr Leu Ser Gly Val Gly Ser Val Asp Asn Phe Tyr Glu Ala
20 25 30
Val Gly Lys Ala Gln Tyr Ala Leu Ser Ser Gln Asn Lys Phe Glu Phe
35 40 45
Val Ser Arg Met Gly Asp Met Tyr Leu Tyr Ser Leu Lys Lys Leu Glu
50 55 60
Asn Met Pro Glu Ile Lys Gly Val Lys Ile Glu Tyr Thr Gly Cys Lys
65 70 75 80
Ser Leu Asp Ile Lys Asn His Lys Glu Val Tyr Ser Asn Leu Ile Val
85 90 95
Tyr Tyr Ile Asn Lys Ile Leu Lys Asn Lys Lys Ile Tyr Asp Lys Thr
100 105 110
Glu Glu Lys Glu Val Glu Lys Tyr Lys Ile Lys Phe Arg Lys Ser Ile
115 120 125
Leu Asn Pro Val Ile Leu Gln Lys Glu Glu Asn Lys Lys Ile Tyr Thr
130 135 140
Ser Ile Val Asn Arg Asp Gly Ile Arg Val Tyr Arg Val Phe Asp Ile
145 150 155 160
Met Pro Phe Ile Asp Asp His Gly Tyr Ala Tyr Leu Arg Cys Asp Ile
165 170 175
Asn His Ile Phe Glu Ser Asp Lys Thr Ile Tyr Asp Met Met Lys Glu
180 185 190
Asn Lys Asn Val Ile Gly Leu Lys Val Asp Tyr Leu Trp Thr Asn Asn
195 200 205
Thr Asn Ser Thr Gly Ile Ile Glu Gly Ile Leu Asp Lys Thr Ile Ser
210 215 220
Asp Lys Leu Ser Glu Leu Lys Gly Gln Ser Leu Ile Asp Tyr Phe Ile
225 230 235 240
Asn Asn Lys Gln Gly Tyr Arg Val Asn Lys Phe Thr Glu Glu Asp Lys
245 250 255
Lys Ala Asn Val Ile Lys Val Lys Gly His Lys Asn Thr Phe Tyr Phe
260 265 270
Ile Pro His Ser Leu Lys Gln Val Ile Asp Arg Glu Ser Leu Lys Ser
275 280 285
Ile Asp Ser Lys Phe Ser Ser Asp Ile Glu Lys Tyr Ile Lys Met Asp
290 295 300
Met Asn Tyr Arg Met Arg Ser Leu Ser Asp Phe Leu Asp Asp Ile Gly
305 310 315 320
Glu Ile Lys Glu Leu Glu Asn Leu Arg Phe Asp Phe Asn Leu Asn Ser
325 330 335
Ile Asp Lys Leu Gly Phe Lys Gln Gly Lys Ile Asp Lys Pro Cys Phe
340 345 350
Leu Val Ser Asn Gly Lys Val Ile Lys Asn Lys Lys Glu Val Phe Cys
355 360 365
Lys Gly Tyr Tyr Leu Lys Pro Asn Asn Lys Ile Arg Val Ala Ile Met
370 375 380
Cys Pro Glu Gly Tyr Val Glu Glu Ser Lys Asn Ala Leu Ser Lys Ile
385 390 395 400
Leu Ser Phe Asn Lys Asn Gly Tyr Ile Val Ser Asn Asp Lys Thr Glu
405 410 415
Gln Lys Asn Phe Ala Ile Lys Ser Leu Leu Asp Leu Glu Tyr Thr Gly
420 425 430
Ile Phe Cys Lys Tyr Lys Leu Gly Asp Ile Thr Glu Tyr Lys Arg Ile
435 440 445
Ala Gly Asn Leu Ile Lys Ser Glu Lys Glu Phe Asp Leu Val Leu Cys
450 455 460
Val Ile Pro Asn Lys Ser Asp Glu Ser Asn Pro Tyr Ser Glu Phe Lys
465 470 475 480
Lys Ile Trp Ala Lys His Asn Ile Pro Ser Gln Met Ile Cys Ile Asp
485 490 495
Ser Leu Lys Ile Ile Asn Asn Cys Lys Asp Leu Asn Asn Tyr Asn Gly
500 505 510
Ile Tyr Tyr Ile Tyr Glu Ile Ser Leu Gly Ile Leu Ala Lys Ser Gly
515 520 525
Gly Val Pro Trp Gly Leu Lys Glu Ile Asn Ser Asp Val Asp Cys Phe
530 535 540
Val Gly Leu Asp Val Gly Asn Pro Tyr Lys Gly Ile Arg Tyr Pro Ser
545 550 555 560
Ser Ser Val Val Phe Asp Lys Asn Gly Thr Leu Ile Asn Tyr Phe Lys
565 570 575
Pro Glu Ile Pro Gln Thr Gly Glu Ile Ile Val Glu Gly Ile Leu Gln
580 585 590
Glu Ile Phe Asp Glu Ile Ile Leu Ser Tyr Asp Arg Lys Phe Lys Gln
595 600 605
Lys Pro Lys His Ile Val Ile His Arg Asp Gly Phe Ala Arg Glu Asn
610 615 620
Ile Asn Trp Tyr Ile Asn Tyr Phe Ser Gln Lys Asn Ile Lys Phe Asp
625 630 635 640
Ile Val Glu Val Lys Lys Gln Gly Ala Val Lys Phe Ala Ile Lys Asp
645 650 655
Lys Glu Ile Phe Lys Asn Pro Glu Ala Gly Cys Tyr Leu Thr Asn Gly
660 665 670
Lys Tyr Ala Tyr Leu Ile Thr Asn Asp Ile Lys Ile Gly Ser Pro Arg
675 680 685
Pro Leu Lys Ile Glu Lys Val Tyr Gly Asp Thr Ser Leu Asp Asp Ile
690 695 700
Val Lys Gln Ile Phe Tyr Leu Ser Glu Leu His Val Gly Ser Phe Lys
705 710 715 720
Lys Thr Arg Leu Pro Ile Thr Thr Glu Tyr Ala Asp Arg Ile Ser Lys
725 730 735
Asn Ile Met Tyr Ile Pro Ser Gly Cys Leu Ser Glu Lys Leu Phe Phe
740 745 750
Leu
<210> 43
<211> 734
<212> PRT
<213> artificial sequence
<400> 43
Val Gly Leu Asp Arg Glu Phe Asn Val Ile Thr Glu Phe Lys Asn Glu
1 5 10 15
Leu Lys Pro Glu Asp Ile Lys Ile Phe Leu Tyr Ser Met Pro Ile Lys
20 25 30
Asp Ile Asn Glu Arg His Ser Glu Asn Tyr Ala Ile Val Gln Glu Leu
35 40 45
Lys Lys Ile Asn Glu Asn Pro Asn Ile Val Phe Asn Glu Tyr Ile Ile
50 55 60
Ala Ser Phe Asn Pro Ile Ile Asn Trp Gly Lys Tyr Lys Asp Ile Asp
65 70 75 80
Val Lys Pro Asp Asn Arg Asn Ile Asp Leu Asp Asn Ser Thr Glu Arg
85 90 95
Lys Ile Leu Glu Arg Leu Leu Leu Cys Asp Ile Lys Asn Asn Ile Asn
100 105 110
Asn Thr Thr Trp Glu Gln Gln Asn Lys Tyr Glu Ile Arg Gly Asn Ala
115 120 125
Asn Pro Ala Val Tyr Leu Arg Lys Pro Ile Tyr Leu Asn Asn Asn Leu
130 135 140
Ile Ile Arg Arg Lys Leu Asn Phe Asp Val Asn Ile Asp Lys Lys Asp
145 150 155 160
Ile Ile Ile Gly Phe Phe Leu Asn His Glu Phe Glu Tyr Gln Lys Thr
165 170 175
Leu Asp Glu Glu Ile Lys Cys Gly Asn Ile Gln Lys Gly Asp Lys Val
180 185 190
Lys Asp Phe Tyr Asn Asn Ile Thr Tyr Glu Phe Leu Glu Met Ala Pro
195 200 205
Phe Ser Ile Ser Gln Glu Asn Lys Tyr Met Arg Ser Ser Ile Ile Glu
210 215 220
Tyr Tyr Leu Asn Lys Gly Gln Ser Tyr Ile Ile Ser Gly Leu Asp Lys
225 230 235 240
Asn Thr Lys Ala Val Leu Val Lys Asn Lys Glu Gly Ser Ile Phe Pro
245 250 255
Tyr Ile Pro Asn Arg Leu Lys Lys Ile Cys Val Phe Glu Asn Leu Gly
260 265 270
Asn Lys Arg Ile Ile Glu Gly Asn Lys Tyr Ile Lys Met Asn Pro Ser
275 280 285
Gln Asn Met Ser Glu Ser Ile Lys Leu Ala Glu Asp Ile Leu Lys Asn
290 295 300
Ser Lys Tyr Val Lys Phe Asn Lys Ala Asn Met Ile Val Glu Lys Met
305 310 315 320
Gly Tyr Lys Lys Asp Ile Val Lys Arg Pro Ala Leu Lys Phe Gly Lys
325 330 335
Asn Glu Ser Asn Phe Ser Ala Met Tyr Gly Leu Asn Lys Ser Gly Ser
340 345 350
Tyr Glu Gln Lys Asn Ile Glu Ile Asp Tyr Phe Ile Asp Pro Lys Ile
355 360 365
Leu Asn Asn Lys Arg Asp Tyr Gln Ile Val Tyr Ser Phe Leu Asn Asp
370 375 380
Ile Ile Ser Lys Ser Lys Asp Leu Gly Val Glu Ile Asn Thr Asp Lys
385 390 395 400
Ser Tyr Ile Asn Leu Thr Pro Ile Asn Ile Lys Asn Glu Asn Glu Phe
405 410 415
Glu Ser Asp Ile Met Glu Ile Ile Lys Asn Tyr Asn Asn Pro Val Leu
420 425 430
Val Ile Leu Glu Lys Glu Asn Ile Asp Lys Tyr Tyr Glu Thr Leu Lys
435 440 445
Lys Ile Phe Gly Gly Arg Asn Ser Ile Ala Thr Gln Phe Val Asp Leu
450 455 460
Asp Thr Ile Lys Arg Cys Asp Pro Lys Ile Asp Asn Lys Arg Gly Lys
465 470 475 480
Glu Ser Ile Phe Leu Asn Ile Leu Leu Gly Ile Tyr Cys Lys Ser Gly
485 490 495
Ile Gln Pro Trp Val Leu Ala Asn Gly Leu Ser Ala Asp Cys Tyr Ile
500 505 510
Gly Leu Asp Val Cys Arg Glu Asn Asn Met Ser Thr Ala Gly Leu Ile
515 520 525
Gln Val Ile Gly Lys Asp Gly Arg Val Leu Lys Ser Lys Thr Ile Ser
530 535 540
Ser His Gln Ser Gly Glu Lys Ile Gln Ile Asn Ile Ile Lys Asp Ile
545 550 555 560
Ile Phe Glu Ala Lys Gln Ala Tyr Lys Asn Thr Tyr Asn Lys Lys Leu
565 570 575
Glu His Ile Val Phe His Arg Asp Gly Ile Asn Arg Glu Asp Ile Asp
580 585 590
Leu Leu Lys Glu Ile Thr Asn Ser Leu Glu Ile Lys Phe Asp Tyr Val
595 600 605
Glu Val Thr Lys Asn Ile Asn Arg Arg Met Ala Met Leu Glu Lys Ser
610 615 620
Asp Glu Asn Tyr Asn His Arg Asp Lys Glu Asn Lys Lys Trp Ile Thr
625 630 635 640
Glu Ile Gly Met Cys Leu Lys Lys Glu Asn Glu Ala Tyr Leu Ile Thr
645 650 655
Thr Asn Pro Ser Glu Asn Met Gly Met Ala Arg Pro Leu Arg Ile Lys
660 665 670
Lys Val Tyr Gly Asn Gln Asn Ile Asp Asp Ile Val Lys Asp Ile Tyr
675 680 685
Lys Leu Ser Phe Met His Ile Gly Ser Ile Met Lys Ser Arg Leu Pro
690 695 700
Ile Thr Thr His Tyr Ala Asp Leu Ser Ser Ile Tyr Ser His Arg Glu
705 710 715 720
Leu Met Pro Lys Ser Val Asp Asn Asn Ile Leu His Phe Ile
725 730
<210> 44
<211> 744
<212> PRT
<213> artificial sequence
<400> 44
Asn Asn Leu Thr Leu Glu Ala Phe Arg Gly Ile Gly Thr Ile Lys Pro
1 5 10 15
Leu Leu Phe Tyr Arg Tyr Lys Leu Ile Gly Lys Gly Lys Ile Glu Asn
20 25 30
Thr Tyr Lys Thr Ile Arg Asn Ala Gln Asn Arg Met Ser Phe Asn Asn
35 40 45
Lys Phe Lys Ala Thr Phe Ser Lys Asp Glu Ile Ile Tyr Thr Leu Glu
50 55 60
Lys Phe Glu Ile Ile Pro Thr Leu Asp Asp Val Thr Ile Ile Phe Asp
65 70 75 80
Gly Glu Glu Val Leu Pro Ile Lys Asp Asn Asn Lys Ile Tyr Ser Glu
85 90 95
Val Ile Glu Phe Tyr Ile Asn Asn Asn Leu Arg Asn Val Lys Phe Asn
100 105 110
Tyr Lys Tyr Pro Lys Tyr Arg Ala Ala Asn Thr Arg Glu Ile Thr Gly
115 120 125
Asn Val Ile Leu Asp Lys Asp Met Asn Glu Lys Tyr Lys Lys Ser Asn
130 135 140
Lys Gly Phe Glu Leu Lys Arg Lys Phe Ile Ile Ser Pro Lys Val Asp
145 150 155 160
Asp Glu Gly Lys Val Thr Leu Phe Leu Asp Leu Asn Ala Ser Phe Asp
165 170 175
Tyr Asp Lys Asn Ile Tyr Gln Met Ile Lys Ala Gly Ile Asp Val Val
180 185 190
Gly Glu Glu Val Ile Asn Ile Trp Ser Asn Lys Lys Gln Arg Gly Lys
195 200 205
Ile Lys Glu Ile Ser Asp Ile Lys Ile Asn Glu Pro Cys Asn Phe Gly
210 215 220
Gln Ser Leu Ile Asp Tyr Tyr Ile Ser Ser Asn Gln Ala Ser Arg Val
225 230 235 240
Asn Gly Phe Thr Glu Glu Glu Lys Asn Thr Asn Val Ile Ile Val Glu
245 250 255
Ser Gly Lys Ser Arg Leu Ser Tyr Ile Pro His Ala Leu Lys Pro Ile
260 265 270
Ile Thr Arg Glu Tyr Ile Ala Lys Asn Asp Glu Val Phe Ser Lys Glu
275 280 285
Ile Glu Gly Leu Ile Lys Ile Asn Met Asn Tyr Arg Tyr Glu Ile Leu
290 295 300
Lys Arg Phe Val Ser Asp Ile Gly Thr Ile Lys Glu Leu Asn Asn Leu
305 310 315 320
Arg Phe Glu Lys Ile Tyr Met Asp Asn Ile Glu Ser Leu Gly Tyr Glu
325 330 335
Gln Gly Gln Leu Lys Asp Pro Val Leu Ile Gly Gly Lys Gly Ile Leu
340 345 350
Lys Asp Lys Ile His Val Phe Lys Ser Gly Phe Tyr Lys Ser Pro Asn
355 360 365
Asp Glu Ile Lys Phe Gly Val Ile Tyr Pro Arg Gly Tyr Ile Lys Asp
370 375 380
Thr Gln Ser Val Ile Arg Ala Ile Tyr Asp Phe Cys Thr Glu Gly Lys
385 390 395 400
Tyr Gln Gly Lys Asp Asn Ile Phe Ile Asn Asn Lys Leu Met Asn Ile
405 410 415
Lys Phe Ser Asn Lys Glu Cys Val Phe Glu Glu Tyr Glu Leu Asn Asp
420 425 430
Ile Thr Glu Tyr Lys Arg Ala Ala Asn Lys Leu Lys Lys Asn Glu Asn
435 440 445
Ile Lys Phe Val Ile Ala Ile Ile Pro Thr Ile Asn Glu Ser Asp Ile
450 455 460
Glu Asn Pro Tyr Asn Pro Phe Lys Arg Val Cys Ala Glu Ile Asn Leu
465 470 475 480
Pro Ser Gln Met Ile Ser Leu Lys Thr Ala Lys Arg Phe Ser Thr Ser
485 490 495
Arg Gly Gln Ser Glu Leu Tyr Phe Leu His Asn Ile Ser Leu Gly Ile
500 505 510
Leu Gly Lys Ile Gly Gly Val Pro Trp Val Ile Lys Asp Met Pro Gly
515 520 525
Glu Val Asp Cys Phe Val Gly Leu Asp Val Gly Thr Lys Glu Lys Gly
530 535 540
Ile His Tyr Pro Ala Cys Ser Val Leu Phe Asp Lys Tyr Gly Lys Leu
545 550 555 560
Ile Asn Tyr Tyr Lys Pro Thr Ile Pro Gln Ser Gly Glu Ile Ile Lys
565 570 575
Thr Asp Val Leu Gln Glu Ile Phe Asp Lys Val Leu Leu Ser Tyr Glu
580 585 590
Glu Glu Asn Gly Gln Tyr Pro Arg Asn Ile Val Ile His Arg Asp Gly
595 600 605
Phe Ser Arg Glu Asp Leu Glu Trp Tyr Lys Asn Tyr Phe Leu Lys Lys
610 615 620
Asn Ile Glu Phe Ser Ile Val Glu Val Arg Lys Asn Phe Ala Thr Arg
625 630 635 640
Leu Val Asn Asn Phe Asn Asp Glu Val Ser Asn Pro Ser Lys Gly Ser
645 650 655
Phe Ile Leu Arg Asp Asn Glu Ala Ile Val Val Thr Thr Asp Ile Asn
660 665 670
Asp Asn Met Gly Ala Pro Lys Pro Ile Lys Val Glu Lys Thr Tyr Gly
675 680 685
Asp Ile Asp Met Leu Thr Ile Ile Asn Gln Ile Tyr Ala Leu Thr Gln
690 695 700
Ile His Val Gly Ser Ala Lys Ser Leu Arg Leu Pro Ile Thr Thr Gly
705 710 715 720
Tyr Ala Asp Lys Ile Cys Lys Ala Ile Asp Tyr Ile Pro Ser Gly Gln
725 730 735
Val Asp Asn Arg Leu Phe Phe Leu
740
<210> 45
<211> 743
<212> PRT
<213> artificial sequence
<400> 45
Glu Asn Leu Thr Ile Glu Ala Phe Lys Gly Ile Gly Tyr Ile Lys Pro
1 5 10 15
Leu Lys Phe Tyr Glu Tyr Ser Ile Val Pro Lys Cys Glu Ile Asp Asn
20 25 30
Ile His Lys Ile Leu Gly Gln Ala Arg Tyr Lys Met His Ser Tyr Asn
35 40 45
Asn Phe Lys Ala Val Phe Val Lys Asn His Lys Leu Tyr Ala Leu Glu
50 55 60
Lys Leu Ser Ile Pro Lys Met Asp Asn Met Glu Ile Asn Phe Asn Lys
65 70 75 80
Ser Thr Glu Leu Gly Ile Glu Asn Asn Leu Asp Ile Tyr Lys Glu Val
85 90 95
Val Ile Tyr Tyr Ile Asn Asn Ser Leu Arg Gln Val Arg Asn Lys Phe
100 105 110
Gly Tyr Lys Lys Tyr Ile Thr Lys Tyr Thr Asp Glu Ile Ile Cys Asn
115 120 125
Thr Ile Ile Asp Arg Asp Leu Ser Glu Lys Tyr Gln Thr Gln Asn Gly
130 135 140
Ile Tyr Phe Lys Arg Lys Phe Lys Ile Asn Pro Glu Val Leu Lys Asn
145 150 155 160
Gly Glu Val Ile Leu Tyr Ile Ser Cys Ser Ser Asp Phe Ser Thr Gln
165 170 175
Lys Thr Ile Phe Asp Phe Ile Asn Glu Lys Lys Asp Ile Ile Gly Leu
180 185 190
Thr Val Lys Asn Lys Trp Ser Asn Ile Lys Gly Thr Gly Glu Ile Val
195 200 205
Glu Ile Ser Asp Arg Arg Val Gly Glu Val Ser Pro Glu Leu Gly Val
210 215 220
Asn Leu Ile Glu Tyr Tyr Lys Asn Met Asn Gln Ala Tyr Arg Val Asn
225 230 235 240
Gln Phe Thr Glu Glu Asp Lys Asn Ala Asn Val Ile Lys Val Lys Thr
245 250 255
Gly Lys Lys Ile Tyr Glu Phe Ile Pro His Ser Leu Glu Pro Ile Ile
260 265 270
Thr Arg Glu Tyr Leu Lys Lys Tyr Asp Pro Asn Phe Ser Ile Lys Ile
275 280 285
Glu Pro Leu Leu Lys Met Glu Met Ser Tyr Arg Tyr Val Thr Leu Lys
290 295 300
Ser Phe Ile Asn Asp Ile Gly Ser Ile Lys Glu Leu Asn Asp Ile Lys
305 310 315 320
Phe Ile Ala Ser Tyr Phe Asp Asp Val Ser Lys Leu Gly Tyr Ser Lys
325 330 335
Gly Ile Ile Glu Glu Pro Ile Leu Leu Ser Ala Asn Gly Ile Ile Lys
340 345 350
Asn Lys Ile Asn Val Phe Ser Lys Gly Phe Tyr Lys Ile Ser Lys Gln
355 360 365
Lys Val Asn Phe Gly Val Ile Tyr Pro Glu Gly Glu Glu Ile Glu Thr
370 375 380
Gln Lys Thr Ile Arg Ala Ile Phe Asp Phe Leu Lys Glu Gly Lys Tyr
385 390 395 400
His Lys Glu Glu Asn Lys Tyr Ile Lys Lys Asn Leu Leu Tyr Leu Asn
405 410 415
Phe Asp Lys Lys Glu Cys Ile Tyr Glu Glu Tyr Lys Ala Gly Asp Ile
420 425 430
Ile Asp Tyr Lys Lys Ala Ala Leu Arg Leu Lys Glu Tyr Ser Ser Leu
435 440 445
Ser Phe Ile Ile Ala Ile Ile Pro Asn Ile Glu Asp Asp Glu Asn Glu
450 455 460
Asn Pro Tyr Asn Pro Phe Lys Arg Val Trp Ala Glu Leu Gly Ile Pro
465 470 475 480
Ser Gln Met Val Ser Leu Lys Thr Ala Glu Arg Phe Val Asn Ser Thr
485 490 495
Ser Lys Thr Glu Leu Tyr Tyr Leu His Asn Ile Ala Leu Gly Ile Leu
500 505 510
Gly Lys Ile Gly Gly Val Pro Trp Gly Ile Ser Asn Met Pro Gly Asp
515 520 525
Ile Asp Cys Phe Ile Gly Leu Asp Val Gly Thr Arg Glu Lys Gly Ile
530 535 540
His Asn Pro Ala Cys Ser Val Val Phe Asp Lys Tyr Gly Glu Leu Ile
545 550 555 560
Asn Tyr Tyr Lys Pro Thr Ile Pro Gln Ser Gly Glu Ile Ile Gln Thr
565 570 575
Glu Ile Leu Gln Glu Ile Phe Asp Lys Ile Leu Leu Ser Tyr Glu Glu
580 585 590
Lys Tyr Gly Arg Tyr Pro Lys Asn Ile Met Ile His Arg Asp Gly Phe
595 600 605
Ser Arg Glu Asp Leu Asp Trp Tyr Lys Asn Tyr Phe Asp Lys Lys Ser
610 615 620
Ile Asp Phe Thr Ile Val Glu Ile Lys Lys Asn Ile Pro Leu Lys Ile
625 630 635 640
Ala Glu Ile Lys Asn Gly Glu Val Lys Asn Pro Lys Ala Gly Ser Tyr
645 650 655
Ile Leu Lys Glu Asp Lys Ala Tyr Leu Ile Thr Thr Asp Ile Arg Glu
660 665 670
Asn Leu Gly Ser Pro Arg Pro Leu Lys Ile Glu Lys Ile Tyr Gly Lys
675 680 685
Ala Glu Met Met Thr Ile Leu Lys Gln Ile Tyr Phe Leu Ala Asn Val
690 695 700
His Val Gly Ser Thr Lys Ala Leu Arg Leu Pro Ile Thr Val Gly Tyr
705 710 715 720
Ala Asp Lys Ile Cys Lys Ala Ile Asp Phe Ile Pro Ser Gly Val Leu
725 730 735
Asp Asn Arg Leu Phe Phe Leu
740
<210> 46
<211> 704
<212> PRT
<213> artificial sequence
<400> 46
Lys Glu Phe Asn Val Ile Thr Glu Phe Lys Asn Gly Ile Asn Ser Lys
1 5 10 15
Ser Ile Glu Ile Tyr Ile Tyr Lys Met Met Val Arg Asp Phe Glu Lys
20 25 30
Arg His Asn Glu Asn Tyr Asp Val Val Lys Glu Leu Ile Asn Leu Asn
35 40 45
Asn Asn Ser Thr Ile Val Phe Tyr Glu Gln Tyr Ile Ala Ser Phe Lys
50 55 60
Glu Ile Glu Lys Trp Gly Asn Glu Gln Tyr Ile Asn Val Glu Lys Arg
65 70 75 80
Ala Ile Asn Leu Glu Ser Asn Glu Lys Lys Ile Leu Glu Arg Leu Leu
85 90 95
Leu Lys Glu Ile Lys Asn Asn Ile Asp Asn Asn Lys Tyr Lys Val Val
100 105 110
Lys Asp Ser Ile Tyr Ile Asn Lys Pro Val Tyr Asn Glu Lys Gly Ile
115 120 125
Lys Ile Asp Arg Tyr Phe Asn Leu Asp Ile Asn Val Glu Ser Asn Gly
130 135 140
Asp Ile Ile Ile Gly Phe Asp Ile Ser His Asn Phe Glu Tyr Ile Asn
145 150 155 160
Thr Leu Glu Tyr Glu Ile Lys Asn Asn Asn Ile Lys Ile Gly Asp Arg
165 170 175
Val Lys Asp Tyr Phe Tyr Asn Leu Thr Tyr Glu Tyr Val Gly Ile Ala
180 185 190
Pro Phe Thr Ile Ser Glu Glu Asn Glu Tyr Met Gly Cys Ser Ile Val
195 200 205
Asp Tyr Tyr Glu Asn Lys Asn Gln Ser Tyr Ile Val Asn Lys Leu Pro
210 215 220
Lys Asp Met Lys Ala Ile Leu Val Lys Asn Asn Lys Asn Ser Ile Phe
225 230 235 240
Pro Tyr Ile Pro Ser Arg Leu Lys Lys Val Cys Arg Phe Glu Asn Leu
245 250 255
Pro Gln Asn Val Leu Arg Asp Phe Asn Thr Arg Val Lys Gln Lys Thr
260 265 270
Asn Glu Lys Met Gln Phe Met Val Asp Glu Val Ile Asn Ile Val Lys
275 280 285
Asn Ser Glu His Ile Asp Val Lys Lys Lys Asn Met Met Cys Asp Asn
290 295 300
Ile Gly Tyr Lys Ile Glu Asp Leu Gln Gln Pro Asp Leu Leu Phe Gly
305 310 315 320
Asn Ala Arg Ala Gln Arg Tyr Pro Leu Tyr Gly Leu Lys Asn Phe Gly
325 330 335
Val Tyr Glu Asn Lys Arg Ile Glu Ile Lys Tyr Phe Ile Asp Pro Ile
340 345 350
Leu Ala Lys Ser Lys Met Asn Leu Glu Lys Ile Ser Lys Phe Cys Asp
355 360 365
Glu Leu Glu Gln Phe Ser Ser Lys Leu Gly Val Gly Leu Asn Arg Val
370 375 380
Lys Leu Asn Asn Ile Val Asn Phe Lys Glu Ile Arg Met Asp Asn Glu
385 390 395 400
Asp Ile Phe Ser Tyr Glu Ile Arg Lys Ile Val Ser Asn Tyr Asn Glu
405 410 415
Thr Thr Ile Val Ile Leu Ser Glu Glu Asn Leu Asn Lys Tyr Tyr Asn
420 425 430
Ile Ile Lys Lys Thr Phe Ser Gly Gly Asn Glu Val Pro Thr Gln Cys
435 440 445
Ile Gly Phe Asn Thr Leu Ser Tyr Thr Glu Lys Asn Lys Asp Ser Ile
450 455 460
Phe Leu Asn Ile Leu Leu Gly Val Tyr Ala Lys Ser Gly Ile Gln Pro
465 470 475 480
Trp Ile Leu Asn Glu Lys Leu Asn Ser Asp Cys Phe Ile Gly Leu Asp
485 490 495
Val Ser Arg Glu Asn Lys Val Asn Lys Ala Gly Val Ile Gln Val Val
500 505 510
Gly Lys Asp Gly Arg Val Leu Lys Thr Lys Val Ile Ser Ser Ser Gln
515 520 525
Ser Gly Glu Lys Ile Lys Leu Glu Thr Leu Arg Glu Ile Val Phe Glu
530 535 540
Ala Ile Asn Ser Tyr Glu Asn Thr Tyr Arg Cys Lys Pro Lys His Ile
545 550 555 560
Thr Phe His Arg Asp Gly Ile Asn Arg Glu Glu Leu Glu Asn Leu Lys
565 570 575
Asn Thr Met Thr Asn Leu Gly Val Glu Phe Asp Tyr Ile Glu Ile Thr
580 585 590
Lys Gly Ile Asn Arg Arg Ile Ala Thr Ile Ser Glu Gly Glu Glu Trp
595 600 605
Lys Thr Ile Met Gly Arg Cys Tyr Tyr Lys Asp Asn Ser Ala Tyr Val
610 615 620
Cys Thr Thr Lys Pro Tyr Glu Gly Ile Gly Met Ala Lys Pro Ile Arg
625 630 635 640
Ile Arg Arg Val Phe Gly Thr Leu Asp Ile Glu Lys Ile Val Glu Asp
645 650 655
Ala Tyr Lys Leu Thr Phe Met His Val Gly Ala Ile Asn Lys Ile Arg
660 665 670
Leu Pro Ile Thr Thr Tyr Tyr Ala Asp Leu Ser Ser Thr Tyr Gly Asn
675 680 685
Arg Asp Leu Ile Pro Thr Asn Ile Asp Thr Asn Cys Leu Tyr Phe Ile
690 695 700
<210> 47
<211> 744
<212> PRT
<213> artificial sequence
<400> 47
Asn Asn Leu Met Leu Glu Ala Phe Lys Gly Ile Gly Thr Ile Lys Pro
1 5 10 15
Leu Val Phe Tyr Arg Tyr Lys Leu Ile Gly Lys Gly Lys Ile Glu Asn
20 25 30
Thr Tyr Lys Thr Ile Ser Asn Ala Lys Asn Lys Met Ser Phe Asn Asn
35 40 45
Lys Phe Lys Ala Thr Phe Ser Lys Gly Glu Thr Ile Tyr Thr Leu Glu
50 55 60
Lys Phe Glu Val Met Pro Asn Leu Asn Asp Val Thr Ile Glu Phe Asp
65 70 75 80
Gly Glu Glu Val Leu Pro Ile Lys Asp Asn Asn Glu Ile Tyr Ser Glu
85 90 95
Val Val Gln Phe Tyr Ile Asn Asn Asn Leu Arg Lys Ile Lys Leu Asp
100 105 110
Asn Lys Tyr Gln Lys Tyr Arg Ala Thr Asn Thr Arg Glu Ile Thr Gly
115 120 125
Asn Val Ile Leu Asp Lys Asp Phe Lys Glu Lys Tyr Lys Lys Ser Lys
130 135 140
Ser Gly Phe Gln Leu Lys Arg Lys Phe Ile Ile Ser Pro Lys Val Asn
145 150 155 160
Asp Glu Gly Lys Val Thr Leu Phe Leu Asp Leu Asn Ser Ser Phe Asp
165 170 175
Tyr Asp Lys Asn Ile Tyr Gln Met Ile Lys Ala Gly Met Asp Val Val
180 185 190
Gly Gln Glu Val Ile Asn Thr Trp Asn Asn Lys Lys Gln Lys Gly Lys
195 200 205
Ile Lys Lys Ile Ser Glu Leu Thr Ile Ser Glu Pro Cys Asn Phe Gly
210 215 220
Gln Ser Leu Ile Asp Tyr Tyr Val Ser Leu Asn Gln Ala Val Arg Val
225 230 235 240
Lys Asn Phe Thr Glu Glu Glu Lys Asn Thr Asn Val Ile Val Val Gln
245 250 255
Val Gly Lys Gly Glu Val Glu Tyr Ile Pro His Ala Leu Lys Pro Ile
260 265 270
Ile Thr Arg Glu Tyr Ile Lys Lys Tyr Asp Glu Ala Phe Ser Lys Glu
275 280 285
Val Glu Asn Leu Ile Lys Ile Asn Met Ser Tyr Arg Tyr Glu Ile Leu
290 295 300
Lys Lys Phe Ile Asp Asp Ile Gly Ser Ile Thr Glu Leu Asn Asn Leu
305 310 315 320
Lys Phe Glu Asn Thr Tyr Ile Asp Asn Ile Glu Ser Leu Gly Tyr Gln
325 330 335
Gln Gly Lys Leu Asn Asp Pro Val Leu Ile Gly Gly Lys Gly Ile Leu
340 345 350
Lys Asp Lys Ile His Val Phe Lys Ser Gly Phe Tyr Lys Ser Pro Ile
355 360 365
Asp Glu Val Lys Phe Gly Val Ile Tyr Pro Lys Gly His Thr Asn Asp
370 375 380
Ser Lys Ser Thr Ile Arg Ala Ile Tyr Asp Phe Cys Thr Asp Gly Lys
385 390 395 400
Tyr Gln Gly Lys Asp Asn Ile Phe Ile Asn Asn Lys Leu Met Asn Ile
405 410 415
Lys Phe Ser Asn Gln Asp Cys Val Phe Glu Glu Tyr Glu Leu Asn Asp
420 425 430
Ile Thr Glu Tyr Lys Arg Ala Ala Asn Lys Leu Lys Asn Asn Glu Asn
435 440 445
Ile Lys Phe Val Ile Ala Ile Ile Pro Ala Ile Asp Glu Ser Asp Ile
450 455 460
Glu Asn Pro Tyr Asn Pro Phe Lys Arg Val Cys Ala Glu Leu Asn Leu
465 470 475 480
Pro Ser Gln Met Val Ser Leu Lys Thr Ala Lys Arg Phe Gly Thr Ser
485 490 495
Lys Gly Asn Asn Glu Leu Tyr Phe Leu His Asn Ile Ser Leu Gly Ile
500 505 510
Leu Gly Lys Ile Gly Gly Val Pro Trp Val Ile Lys Asp Met Pro Gly
515 520 525
Glu Val Asp Cys Phe Val Gly Leu Asp Val Gly Thr Lys Glu Lys Gly
530 535 540
Ile His Tyr Pro Ala Cys Ser Val Leu Phe Asp Lys Tyr Gly Lys Leu
545 550 555 560
Ile Asn Tyr Tyr Lys Pro Thr Ile Pro Gln Ser Gly Glu Ile Ile Lys
565 570 575
Thr Asp Val Leu Gln Glu Ile Phe Asp Lys Val Leu Leu Ser Tyr Glu
580 585 590
Glu Glu Asn Gly Gln Tyr Pro Arg Asn Ile Val Ile His Arg Asp Gly
595 600 605
Phe Ser Arg Glu Asp Leu Glu Trp Tyr Lys Asn Tyr Phe Ile Lys Lys
610 615 620
Asn Ile Asn Phe Thr Ile Val Glu Ile Lys Lys Asn Phe Ala Thr Arg
625 630 635 640
Val Ala Asn Asn Ile Asn Asn Glu Val Ser Asn Pro Phe Lys Gly Ser
645 650 655
Phe Ile Leu Arg Glu Asn Glu Ala Ile Val Val Thr Thr Asp Ile Lys
660 665 670
Asp Asn Ile Gly Ala Pro Lys Pro Ile Lys Val Glu Lys Thr Tyr Gly
675 680 685
Asp Ile Asp Met Met Thr Ile Ile Asn Gln Ile Tyr Ala Leu Thr Gln
690 695 700
Ile His Val Gly Ser Ala Lys Ser Met Arg Leu Pro Ile Thr Thr Gly
705 710 715 720
Tyr Ala Asp Lys Ile Cys Lys Ser Ile Glu Tyr Ile Pro Ser Gly Arg
725 730 735
Val Asp Asn Arg Leu Phe Phe Leu
740
<210> 48
<211> 704
<212> PRT
<213> artificial sequence
<400> 48
Arg Glu Phe Asn Val Ile Thr Glu Phe Lys Asn Ser Ile Asn Ala Asn
1 5 10 15
Asn Ile Glu Ile Tyr Ile Tyr Lys Met Arg Val Arg Asp Phe Glu Asn
20 25 30
Lys His Asn Glu Asn Tyr Asp Ile Val Lys Glu Leu Ile Lys Leu Asn
35 40 45
Asn Asn Pro Thr Ile Ile Phe Tyr Glu Gln Tyr Ile Ala Ser Phe Ile
50 55 60
Glu Ile Gln Asn Trp Gly Ser Glu Lys Tyr Ile Asp Val Glu Lys Arg
65 70 75 80
Ile Ile Thr Leu Asp Ser Asn Glu Lys Lys Ile Leu Glu Arg Leu Leu
85 90 95
Leu Lys Glu Ile Lys Asp Ser Ile Asp Lys Glu Lys Tyr Lys Val Ile
100 105 110
Lys Asn Ser Ile Tyr Ile Asn Lys Pro Val Tyr Tyr Glu Lys Gly Ile
115 120 125
Lys Ile Asp Arg Tyr Phe Asn Phe Asp Ile Asn Ile Asn Cys Asn Asn
130 135 140
Glu Ile Ile Ile Gly Phe Asp Ala Lys His Ile Phe Glu Tyr Ile Asn
145 150 155 160
Thr Leu Glu Cys Glu Ile Lys Asn Asp Asn Val Lys Ile Gly Asp Lys
165 170 175
Val Lys Asp Tyr Phe Tyr Asn Leu Thr Tyr Glu Tyr Val Gly Ile Ala
180 185 190
Pro Phe Thr Ile Ser Glu Ala Asn Glu Tyr Met Gly Cys Ser Ile Ile
195 200 205
Asp Tyr Tyr Glu Asn Lys Asn Gln Gly Tyr Ile Val Asn Lys Leu Pro
210 215 220
Lys Asp Met Lys Ala Val Leu Val Lys Asn Asn Lys Asn Ser Ile Phe
225 230 235 240
Pro Tyr Ile Pro Ser Arg Leu Lys Lys Val Cys Arg Phe Glu Asn Leu
245 250 255
Pro Gln Asn Val Leu Lys Asp Phe Asn Asn Arg Val Lys Gln Lys Thr
260 265 270
Asn Glu Lys Met Gln Phe Met Val Ser Glu Val Ile Asn Ile Val Lys
275 280 285
Asn Ser Glu His Ile Asn Val Glu Lys Ile Asn Met Leu Cys Gly Asn
290 295 300
Ile Gly Tyr Lys Leu Lys Asp Leu Gln His Pro Asp Leu Leu Phe Gly
305 310 315 320
Asn Ser Arg Ala Gln Lys Tyr Pro Leu Tyr Gly Leu Lys Asn Phe Gly
325 330 335
Val Tyr Glu Asn Lys Thr Ile Glu Ile Lys Tyr Phe Ile Asp Pro Ile
340 345 350
Leu Ala Lys Asn Asn Ile Asn Leu Lys Lys Val Ile Lys Phe Cys Asp
355 360 365
Glu Leu Glu Cys Phe Ser Asn Met Leu Gly Val Lys Leu Asp Arg Val
370 375 380
Lys Leu Lys Asp Lys Val Asn Phe Lys Glu Ile Lys Ile Asp Asn Glu
385 390 395 400
Asp Ile Phe Ser Tyr Glu Leu Lys Lys Ile Ala Ser Asn Tyr Asn Glu
405 410 415
Thr Thr Ile Val Ile Leu Ser Glu Glu Asn Leu Ser Lys Tyr Tyr Asn
420 425 430
Ile Ile Lys Lys Thr Phe Ser Gly Gly Asn Glu Ile Pro Thr Gln Cys
435 440 445
Ile Gly Phe Asp Thr Leu Ser Tyr Asn Glu Lys Asn Lys Asp Ser Ile
450 455 460
Phe Phe Asn Ile Leu Leu Gly Ile Tyr Ala Lys Ser Gly Ile Gln Pro
465 470 475 480
Trp Ile Leu Lys Glu Lys Leu Asn Ser Asp Cys Phe Ile Gly Leu Asp
485 490 495
Val Ser Arg Glu Asn Lys Val Asn Lys Ala Gly Val Ile Gln Val Val
500 505 510
Gly Lys Asp Gly Lys Val Leu Lys Thr Lys Val Ile Ser Ala Ser Gln
515 520 525
Ser Gly Glu Lys Ile Lys Leu Glu Thr Leu Lys Glu Ile Val Phe Glu
530 535 540
Ala Val Gly Ser Tyr Glu Asn Ala Tyr Gly Cys Arg Pro Lys His Ile
545 550 555 560
Thr Phe His Arg Asp Gly Ile Ser Arg Glu Glu Leu Glu Asn Leu Lys
565 570 575
Asn Thr Met Asn Asn Leu Gly Ile Glu Phe Asp Tyr Ile Glu Ile Thr
580 585 590
Lys Gly Ile Asn Arg Arg Ile Ala Thr Ile Ser Asp Asp Lys Gln Trp
595 600 605
Lys Thr Val Met Gly Arg Cys Tyr Tyr Lys Asp Asp Ser Ala Phe Ile
610 615 620
Cys Thr Thr Lys Pro Tyr Glu Gly Met Gly Met Ala Gln Pro Ile Arg
625 630 635 640
Ile Arg Arg Val Phe Gly Ser Leu Asp Ile Glu Lys Ile Val Glu Asp
645 650 655
Ala Tyr Lys Leu Thr Phe Met His Val Gly Ala Ile Asn Lys Val Arg
660 665 670
Leu Pro Ile Thr Thr Tyr Tyr Ala Asp Leu Ser Ser Thr Tyr Gly Asn
675 680 685
Arg Asp Leu Ile Pro Ser Asn Ile Asp Thr Asn Cys Leu Tyr Phe Ile
690 695 700
<210> 49
<211> 737
<212> PRT
<213> artificial sequence
<400> 49
Asp Leu Lys Leu Glu Val Phe Ala Ser Lys Thr Arg Ile Glu Pro Val
1 5 10 15
Ser Leu His Val Tyr Gln Leu Ile Ser Gln Asn Ile Glu Asp Asn Lys
20 25 30
Tyr Lys Ile Ile Arg Gly Ala Ser Trp Lys Ile Arg Asn Tyr Asn His
35 40 45
Cys Gly Val Phe Glu Asn Gly Glu Tyr Ile Tyr Thr Thr Glu Leu Val
50 55 60
Lys Asn Asp Ile Pro Asn Ala Asp Phe Glu Leu Glu Tyr Lys Gly Lys
65 70 75 80
Gln Glu Leu Glu Val Gly Lys Asn Gln Arg Val Tyr Gly Glu Leu Ile
85 90 95
Lys Tyr Cys Ile Phe Arg Lys Leu Glu Thr Val Leu Ile Ala Glu Lys
100 105 110
Tyr Arg Lys Tyr Ala Cys Arg Asn Glu Ile Thr Ser Lys Phe Ile Met
115 120 125
Thr Glu Asn Gly Phe Gln Thr Tyr Ser Ser Arg Asn Lys Glu Ile Ser
130 135 140
Leu Glu Arg Gln Tyr Lys Leu Trp Val Ser Val Lys Glu Asp Gly Tyr
145 150 155 160
Thr Tyr Leu His Ile Asp Thr Ser Ser Met Phe Ser Ser Arg Leu Thr
165 170 175
Val Ala Asp Tyr Leu Ser Ala Gly Lys Ser Val Val Gly Met Thr Val
180 185 190
Lys Asn Asp Trp Ala Lys Asn Lys Gln Thr Gly Thr Ile Thr Glu Val
195 200 205
Cys Gly Phe Thr Val Thr Asp Ser Leu Asn Phe Ala Arg Ser Leu Lys
210 215 220
Asp Tyr Tyr Val Lys Lys Gly Glu Glu Tyr Arg Val Lys Asp Ile Ser
225 230 235 240
Asp Asn Thr Pro Val Ile Lys Val Lys Leu Leu Gly Gly Ser Glu Leu
245 250 255
Pro Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr Arg Glu Met Val
260 265 270
Gly Ile Leu Asp Pro Glu Phe Ser Leu Lys Ile Asp Lys Tyr Val Lys
275 280 285
Arg Asp Met Arg Thr Arg Leu Gln Leu Asp Ala Asp Phe Ile Gln Asp
290 295 300
Ile Gly Ala Ile Gln Glu Leu Gly Gly Phe Glu Phe Glu Arg Asp Cys
305 310 315 320
Cys Pro Ala Asp Arg Leu Gly Tyr Arg Pro Gly Val Val Tyr Leu Pro
325 330 335
Ala Leu Thr Cys Gly Glu Gly His Thr Val Asp Cys Gly Lys Glu Ile
340 345 350
Gln Val Phe Gln His Gly Phe Tyr Lys Lys Pro Asp Lys Lys Ile Lys
355 360 365
Ile Gly Tyr Leu Tyr Pro Thr Gly Met Lys Asn Leu Met Lys Ala Val
370 375 380
Ala Asn Ser Ile Tyr Thr Phe Ser Thr Lys Gly Tyr Tyr His Gly Gln
385 390 395 400
Lys Asp Cys Tyr Thr Arg Glu Gly Leu Leu Asp Ile Gln Ser Arg Ala
405 410 415
Met Ile Gln Glu Glu Tyr Glu Leu Gly Asp Ile Thr Asp Tyr Lys Arg
420 425 430
Ala Ala Asn Lys Ile Lys Lys Leu Asp Glu Val Asp Ile Val Ile Ala
435 440 445
Ile Val Pro Asp Asp Met Glu Asp Asp Gly Pro Tyr Asn Pro Phe Lys
450 455 460
Thr Ile Trp Ala Glu Ala Asn Ile Pro Ser Gln Met Val Ser Val Arg
465 470 475 480
Thr Ala Lys Met Phe Glu Arg Glu Thr Thr Ala Ser Thr Ser Lys Tyr
485 490 495
Tyr Leu His Asn Ile Val Leu Gly Ile Leu Gly Lys Ile Gly Gly Ile
500 505 510
Pro Trp Ile Ile Lys Asp Met Pro Gly Asn Ala Asp Cys Phe Val Gly
515 520 525
Leu Asp Val Ala Thr Ala Asp Thr Gly Ile His Phe Pro Ala Cys Ser
530 535 540
Val Val Phe Asp Lys Tyr Gly Arg Leu Leu Gly Phe Tyr Lys Pro Lys
545 550 555 560
Gln Ala Gln Arg Gly Glu Lys Ile Thr Thr Arg Ile Leu Gln Asp Ile
565 570 575
Phe Asp Gln Val Ile Phe Ser Tyr Glu Glu Ala Phe Gly Glu Thr Pro
580 585 590
Lys Arg Ile Met Ile His Arg Asp Gly Phe Ser Asn Glu Asn Asp Glu
595 600 605
Trp Tyr Gln Thr Tyr Phe Ser Ala Lys Gly Ile Phe Tyr Thr Ile Val
610 615 620
Glu Val Arg Lys Asn Ile Ser Ser Lys Leu Val Met Tyr Gln Asp Gly
625 630 635 640
Val Val Leu Asn Pro Gly Ile Gly Tyr Cys Val Tyr Asn Gln Lys Glu
645 650 655
Ala Tyr Leu Val Thr Thr Asp Met Lys Arg Lys Lys Gly Ser Pro Asn
660 665 670
Pro Leu Arg Ile Glu Lys Lys Cys Gly Asp Thr Ser Met Thr Asp Ile
675 680 685
Ile Arg Gln Ile Leu Tyr Leu Thr Gln Leu His Val Gly Ser Thr Gln
690 695 700
Lys Met Arg Leu Pro Val Thr Thr Gly Tyr Ala Asp Lys Ile Cys Lys
705 710 715 720
Asn Arg Glu Phe Val Pro Glu Gly Arg Val Asp Asn Lys Leu Phe Phe
725 730 735
Leu
<210> 50
<211> 741
<212> PRT
<213> artificial sequence
<400> 50
Leu Lys Met Glu Val Phe Ala Ser Lys Glu Pro Val Lys Ser Val Lys
1 5 10 15
Leu His Val Tyr Glu Phe His Thr Ser Glu Leu Tyr Glu Asn Lys Tyr
20 25 30
Arg Leu Ile Arg Ser Ala Val Trp Lys Met Arg Asn Val Asn Ala Cys
35 40 45
Gly Val Phe Glu Asp Gly Ser Tyr Ile Tyr Thr Thr Glu Lys Ile Ser
50 55 60
Glu Glu Ile Pro Asn Ala Thr Phe Arg Leu Thr Tyr Leu Gly Glu Gln
65 70 75 80
Glu Leu Asn Val Leu Asp His Lys Lys Val Tyr Ser Glu Leu Ile Lys
85 90 95
His Trp Ile Thr Gln Lys Leu Arg Thr Val Lys Ile Gln Lys Asn Ser
100 105 110
Lys Glu Tyr Tyr Lys Tyr Ala Cys Arg Ser Asn Val Thr Ser Arg Trp
115 120 125
Ile Gln Thr Glu Lys Gly Phe Gln Thr Phe Tyr Ser Gly Asn Arg Gln
130 135 140
Ile Ser Leu Glu Arg Lys Tyr Asn Phe Thr Val Lys Ile Leu Asp Asp
145 150 155 160
Gly Lys Ala Tyr Leu Lys Ile Asp Thr Ser Ser Val Phe Ser Ser Asn
165 170 175
Gln Thr Val Tyr Asp Tyr Ile Thr Gln Gly Met Asn Pro Ile Gly Met
180 185 190
Glu Val Lys Asn Glu Trp Gly Lys Asn Asn Gln Thr Gly Ile Leu Thr
195 200 205
Glu Ile Cys Asp Tyr Thr Val Val Asn Lys Ile Asp Phe Ala Asp Ser
210 215 220
Leu Lys Ala Tyr Tyr Thr Asp Met Lys Lys Glu Gly Tyr Arg Val Glu
225 230 235 240
Asn Leu Pro Asp Gln Thr Pro Val Val Arg Val Glu Leu Gln Val Gly
245 250 255
Lys Ile Tyr Pro Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr Arg
260 265 270
Glu Lys Val Gly Gln Ile Asp Ala Arg Phe Ser Met Ala Ile Glu Lys
275 280 285
Tyr Ile Lys Arg Asp Met Ile Thr Arg Ile Glu Leu Asp Lys Asp Phe
290 295 300
Ile Gln Asp Ile Gly Ser Ile Ala Gln Leu Gly Asp Leu Glu Phe Glu
305 310 315 320
Asn Asp Met Cys Asn Val Lys Glu Leu Gly Tyr Leu Lys Gly Lys Val
325 330 335
Glu Ser Pro Ala Leu Thr Cys Gly Gln Gly Lys Arg Leu Arg Cys Gly
340 345 350
Glu Glu Phe Lys Val Phe Asn Tyr Gly Phe Tyr Gln Lys Pro Asp Glu
355 360 365
Lys Ile Lys Ile Gly Tyr Ile Tyr Pro Lys Asn Thr Val Asp Leu Ile
370 375 380
Lys Ala Val Val Asn Gly Ile Cys Glu Phe Ala Ala Tyr Gly Lys Tyr
385 390 395 400
Gln Gly Glu Lys Asp Ala Tyr Ile Ile Pro Gly Leu Leu Asp Ile Gln
405 410 415
Met Lys Pro Met Ile Lys Glu Glu Tyr Glu Leu Gly Asp Ile Thr Asp
420 425 430
Tyr Lys Arg Ala Ala Gln Arg Leu Arg Lys Val Glu Gly Ile Asp Ile
435 440 445
Val Ile Gly Ile Val Pro Asp Gly Met Asp Glu Asp Gly Pro Tyr Asn
450 455 460
Pro Phe Lys Thr Ile Trp Ala Glu Ala Asn Ile Pro Ser Gln Met Ile
465 470 475 480
Ser Met Lys Thr Ala Gln Leu Phe Tyr Arg Gly Lys Arg Glu Gly Asn
485 490 495
Lys Ser Lys Tyr Tyr Leu His Asn Ile Val Leu Gly Ile Leu Gly Lys
500 505 510
Thr Gly Gly Ile Pro Trp Val Ile Lys Glu Met Pro Gly Asn Val Asp
515 520 525
Cys Phe Val Gly Leu Asp Val Ala Ile Leu Glu Lys Gly Ile His Tyr
530 535 540
Pro Ala Cys Ser Val Val Phe Asp Lys Ser Gly Arg Leu Leu Gly Phe
545 550 555 560
Tyr Lys Pro Lys Ser Ala Gln Arg Gly Glu Lys Ile Glu Thr Arg Ile
565 570 575
Leu Gln Asp Ile Phe Asp Gln Val Leu Leu Ser Tyr Glu Glu Lys Phe
580 585 590
Gly Glu Gln Pro Lys Asn Ile Met Ile His Arg Asp Gly Phe Ser Asn
595 600 605
Glu Asn Asp Ala Trp Tyr Glu Lys Tyr Phe Gly Ala Lys Gly Ile Ala
610 615 620
Tyr Thr Ile Val Glu Val Arg Lys Asn Ile Ser Ser Lys Leu Ala Ile
625 630 635 640
Ile Glu Asp Gly Val Ile Lys Asn Pro Glu Met Gly Tyr Cys Ile Tyr
645 650 655
Asn Asn Asn Lys Gly Tyr Leu Val Thr Thr Asn Met Lys Asn Lys Lys
660 665 670
Gly Ser Pro Asn Pro Leu Leu Leu Glu Lys Lys Cys Gly Asp Val Pro
675 680 685
Met Thr Ile Ile Leu Lys Gln Val Leu Tyr Leu Ser Gln Leu His Val
690 695 700
Gly Ser Thr Gln Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp
705 710 715 720
Lys Ile Cys Lys Asn Arg Glu Phe Val Pro Glu Gly Lys Met Asp Asn
725 730 735
Arg Leu Phe Phe Leu
740
<210> 51
<211> 737
<212> PRT
<213> artificial sequence
<400> 51
Asp Leu Arg Met Glu Val Phe Ser Ser Lys Asp Ile Val Arg Ala Thr
1 5 10 15
Cys Leu His Val Tyr Gln Leu His Thr Gln Lys Ile Asp Asn Thr Phe
20 25 30
Ser Ile Ile Arg Gly Ala Ala Trp Lys Leu Arg Asn Tyr Phe His Val
35 40 45
Gly Val Phe Glu Asp Gly Lys Arg Ile Tyr Thr Thr Glu Lys Ile Glu
50 55 60
Gly Thr Val Pro Asn Ala Asp Phe Ile Ile Glu Tyr Glu Gly Phe Lys
65 70 75 80
Glu Leu Pro Val Leu Glu Asn Arg Lys Ile Tyr Cys Glu Leu Ile Lys
85 90 95
His Phe Ile Thr Gln Asn Leu Ser Glu Val Met Val Tyr Asp Lys Tyr
100 105 110
Arg Lys Tyr Ser Cys Lys Ser Ser Val Thr Ser Lys Trp Ile Met Thr
115 120 125
Asn Gln Gly Phe Lys Thr Phe Ile Ser Lys Asn Lys Glu Ile Ser Leu
130 135 140
Glu Arg Lys Tyr Asn Phe Trp Val Glu Ile Leu Asp Asn Gly Lys Ala
145 150 155 160
Tyr Leu Arg Leu Asp Thr Gly Ser Val Phe Thr Ser Asn Leu Thr Val
165 170 175
Asn Asp Tyr Leu Val Lys Gly Val Asp Pro Ile Gly Met Glu Val Lys
180 185 190
Asn Asp Trp Ala Lys Asn Asn Gln Thr Gly Ile Leu Thr Glu Ile Cys
195 200 205
Asp Phe Thr Val Thr Asp Lys Leu Asp Phe Thr Asp Ser Leu Lys Ala
210 215 220
Tyr Tyr Ile Glu Arg Lys Glu Gly Tyr Arg Val Glu Lys Ile Pro Asp
225 230 235 240
Asp Thr Lys Val Val Lys Val Glu Leu Gln Pro Gly Lys Ser Tyr Pro
245 250 255
Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr Arg Glu Lys Val Gly
260 265 270
Gln Ile Asp Ala Thr Phe Ser Leu Gln Ile Asp Ser Tyr Val Lys Arg
275 280 285
Asn Met Gln Thr Arg Leu Gln Leu Asp Ile Asp Phe Ile Lys Asp Val
290 295 300
Gly Ser Leu Ser Glu Leu Ser Asp Leu Glu Phe Asn Thr Glu Thr Cys
305 310 315 320
Thr Val Glu Glu Ile Gly Tyr Thr Lys Gly Thr Val Pro Leu Pro Asn
325 330 335
Leu Ile Cys Gly Lys Asp Lys Ala Leu Glu Cys Gly Lys Glu Leu Gln
340 345 350
Val Phe Asn Tyr Gly Phe Tyr Arg Lys Thr Asp Arg Lys Ile Lys Ile
355 360 365
Gly Tyr Ile Tyr Pro Lys Asn Thr Phe Asp Lys Met Lys Ala Val Val
370 375 380
Asn Glu Ile Tyr Ser Phe Ala Lys Leu Gly Lys Tyr Gln Gly Glu Lys
385 390 395 400
Asp Lys Tyr Ile Val Glu Gly Leu Leu Asp Ile Gln Ala Glu Pro Met
405 410 415
Ile Lys Glu Glu Tyr Glu Leu Gly Asp Leu Thr Asp Tyr Lys Arg Ala
420 425 430
Ala Asn Arg Leu Gln Lys Val Lys Gly Ile Asp Ile Val Ile Ala Leu
435 440 445
Ile Pro Asp Gly Ile Asp Glu Asp Gly Pro Tyr Asn Pro Phe Lys Thr
450 455 460
Ile Trp Ala Lys Ala Asn Ile Pro Ser Gln Met Ile Ser Met Lys Thr
465 470 475 480
Ala Glu Leu Phe Ala Arg Gly Lys Ser Glu Gly Asn Lys Ser Lys Tyr
485 490 495
Tyr Leu His Asn Ile Ile Leu Gly Ile Leu Gly Lys Thr Gly Gly Ile
500 505 510
Pro Trp Ile Val Lys Asp Met Pro Gly Asn Val Asp Cys Phe Val Gly
515 520 525
Leu Asp Val Ala Thr Val Ala Lys Gly Ile His Tyr Pro Ala Cys Ser
530 535 540
Val Val Phe Asp Lys Tyr Gly Arg Leu Leu Gly Phe Tyr Lys Pro Thr
545 550 555 560
Thr Pro Gln Gln Gly Glu Lys Ile Thr Thr Arg Ile Leu Gln Asp Ile
565 570 575
Phe Asp Gln Val Ile Phe Ser Tyr Glu Asp Arg Phe Glu Glu Met Pro
580 585 590
Lys Asn Val Val Ile His Arg Asp Gly Phe Ser Asn Glu Asn Asp Asp
595 600 605
Trp Tyr Arg Asn Tyr Phe Gly Ala Lys Gly Ile Glu Tyr Ser Ile Ile
610 615 620
Glu Val Arg Lys Asn Val Ser Ser Lys Leu Ile Leu Leu Gln Asp Asp
625 630 635 640
Lys Ile Met Asn Pro Thr Met Gly Tyr Cys Val Tyr Asn Asn Asn Lys
645 650 655
Gly Tyr Leu Val Thr Thr Asp Met Lys Asn Lys Lys Gly Ser Pro Asn
660 665 670
Pro Ile Leu Val Glu Lys Lys Cys Gly Asn Val Ser Met Ala His Ile
675 680 685
Leu Thr Gln Ile Leu Tyr Leu Ser Gln Leu His Val Gly Ser Thr His
690 695 700
Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp Lys Ile Cys Lys
705 710 715 720
Asn Arg Asp Phe Val Pro Glu Gly Lys Met Asp Asp Arg Leu Phe Phe
725 730 735
Leu
<210> 52
<211> 741
<212> PRT
<213> artificial sequence
<400> 52
Asn Phe Lys Leu Glu Val Phe Glu Ser Asn Lys Ala Ile Lys Pro Ile
1 5 10 15
Gly Phe His Thr Tyr Ser Leu Lys Ser Phe Lys Leu Glu Glu Asn Pro
20 25 30
Phe Lys Val Ile Arg Gly Ala Cys Lys Lys Leu Ala Asn Tyr Asn Ile
35 40 45
Asn Asn Gly Val Tyr Glu Asn Gly Lys Lys Ile Phe Ser Ile Glu Gln
50 55 60
Ile Glu Asn Ile Pro Glu Asn Ala Asp Phe Ser Leu Glu Tyr Glu Gly
65 70 75 80
Ile Thr Val Leu Glu Ile His Glu Asn Lys Lys Val Tyr Glu Glu Tyr
85 90 95
Ile Lys Thr Leu Ile Arg Asn Arg Leu Ser Thr Ile Leu Val Asn Gly
100 105 110
Lys Tyr Lys Lys Tyr Ser Thr Lys Tyr Asn Ile Ser Ser Gly Trp Phe
115 120 125
Lys Asp Ile Lys Gly Asn Trp Asn Leu Ile Lys Ser Asp Asp Gly Ser
130 135 140
Ile Gln Leu Glu Arg Gly Tyr Lys Ile Arg Val Asn Ile Gly Asp Asp
145 150 155 160
Asn Lys Ile Tyr Leu Trp Ile Asn Thr Val Ser Glu Phe Arg Cys Lys
165 170 175
Asp Thr Ile Met Asp Leu Leu Asn Lys Gly Lys Asn Val Ile Gly Tyr
180 185 190
Gln Ile Lys Asn Asp Trp Ala Tyr Phe Ser Gln Thr Gly Val Val Val
195 200 205
Asp Val Trp Asp Lys Thr Val Val Asp Asn Leu Ser Phe Gly Ser Ser
210 215 220
Leu Lys Asp Tyr Tyr Ile Lys Lys Gly Glu Gly Ala Lys Val Met Asp
225 230 235 240
Leu Pro Asn Glu Thr Pro Val Val Gln Val Lys Pro Asn Asn Gly Asn
245 250 255
Asn Asn Ile Ser Tyr Tyr Pro Gln Ala Leu Arg Pro Ile Ile Thr Arg
260 265 270
Glu Lys Ile Ser Glu Ile Asp Ser Asn Phe Ser Met Arg Ile Glu Asp
275 280 285
Leu Val Lys Arg Asp Met Lys Glu Arg Ile Glu Leu Asp Lys Ala Phe
290 295 300
Ile Gln Asp Ile Gly Cys Leu Glu Glu Leu Asp Asn Leu Ser Phe Glu
305 310 315 320
Glu Asn Cys Cys Asp Pro Tyr Arg Leu Gly Tyr Arg Lys Ala Ile Val
325 330 335
Gly Leu Pro Lys Leu Leu Cys Gly Asp Gly Lys Thr Ile Ser Cys Gly
340 345 350
Glu Glu Gln Lys Ile Phe Phe His Gly Phe Tyr Gln Pro Thr Lys Lys
355 360 365
Thr Leu Lys Leu Gly Phe Val Tyr Pro Met Gly Glu Arg Asp Leu Leu
370 375 380
Ile Gln Val Val Asn Glu Ile Tyr Leu Phe Ala Val Lys Gly Cys Tyr
385 390 395 400
His Gly Lys Lys Asp Asn Trp Ile Lys Glu Gly Leu Ile Asn Ile Gln
405 410 415
Lys Gly Thr Asp Ile Ser Lys Asp Tyr Lys Leu Gly Ser Ile Thr Asp
420 425 430
Tyr Lys Arg Ala Ser Arg Glu Leu Ile Lys Gln Glu Glu Val Asp Ile
435 440 445
Val Ile Ala Leu Val Pro Asp Gln Met Asp Asp Glu Asn Pro Tyr Asn
450 455 460
Pro Phe Lys Ser Val Trp Ala Glu His Asn Ile Pro Ser Gln Met Ile
465 470 475 480
Thr Met Lys Thr Ala Lys Lys Phe Val Met Asp Ala Gln Lys Gly Lys
485 490 495
Asn Gly Ser Lys Trp Tyr Leu His Asn Ile Val Leu Gly Ile Leu Gly
500 505 510
Lys Thr Gly Gly Ile Pro Trp Val Val Asp Lys Met Pro Gly Asn Val
515 520 525
Asp Cys Phe Val Gly Leu Asp Val Ala Lys Val Glu Lys Gly Ile His
530 535 540
Phe Pro Ala Cys Ser Val Met Phe Asp Lys Tyr Gly Arg Leu Met Gly
545 550 555 560
Phe Phe Lys Pro Arg Thr Pro Gln Gln Gly Glu Lys Ile Thr Thr Glu
565 570 575
Ile Leu Gln Asp Ile Phe Asp Gln Val Leu Phe Ser Tyr Glu Asp Thr
580 585 590
Tyr Gly Ser Lys Pro Lys Asn Ile Val Ile His Arg Asp Gly Phe Asn
595 600 605
Asn Glu Asp Glu Lys Trp Tyr Gln Asn Tyr Phe Ala Val Gln Gly Ile
610 615 620
Glu Tyr Ser Ile Ile Glu Val Arg Lys Asn Ile Ser Ser Lys Met Leu
625 630 635 640
Asp Glu Glu Val Pro Asn Met Asn Pro Thr Thr Gly Met Cys Ile Tyr
645 650 655
Asn Asp Lys Thr Ala Tyr Leu Val Thr Thr Val Met Lys Asn Lys Lys
660 665 670
Gly Ser Pro Asn Pro Leu Leu Leu Glu Lys Ser His Gly Ser Ile Ser
675 680 685
Met Pro Ala Ala Ile Gln Gln Val Leu Tyr Leu Thr Gln Leu His Val
690 695 700
Gly Ser Thr Gln Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp
705 710 715 720
Lys Ile Cys Lys Asn Leu Asp Tyr Val Pro Ala Gly Gln Val Asp Asn
725 730 735
Lys Leu Phe Phe Leu
740
<210> 53
<211> 744
<212> PRT
<213> artificial sequence
<400> 53
Asp Gly Leu Arg Leu Glu Val Phe Ala Ser Asp Lys Val Val Ser Ile
1 5 10 15
Cys Ser Phe His Ile Tyr Asn Ile Lys Ser Gln Asn Ile Asp Asp Asn
20 25 30
Ser Tyr Lys Ile Ile Arg Gly Ala Cys Ser Lys Leu Ala Asn Val Asn
35 40 45
Arg Arg Leu Gly Ile Phe Glu Asn Gly Ser Gln Ile Ile Ser Thr Asp
50 55 60
Leu Ile Asp Asn Ile Pro Asn Gly Ile Asp Phe Ser Leu Glu Tyr Val
65 70 75 80
Gly Tyr Glu Lys Leu Asp Ile Gln Ser Asn Thr Arg Val Tyr Gly Arg
85 90 95
Tyr Ile Glu Tyr Leu Ile Lys Asn Asn Leu Ser Ser Val Lys Val Leu
100 105 110
Glu Lys Tyr Asn Lys Tyr Ser Cys Lys Ser Asp Ile Thr Ser Ala Trp
115 120 125
Phe Arg Ser Ala Glu Gly Ser Phe Gly Thr Tyr Lys Ser Asp Asp Lys
130 135 140
Ile Ile Ser Leu Glu Arg Ile Tyr Asn Ile His Val Glu Ile Gly Lys
145 150 155 160
Asp Gly Lys Ala Tyr Leu Trp Leu Asp Thr Lys Thr Gly Phe Arg Ser
165 170 175
Lys Leu Thr Val Met Asp Met Leu Glu Lys Arg Ile Asp Val Leu Gly
180 185 190
Met Glu Val Lys Asn Asp Trp Gly Gln Phe Arg Gln Thr Gly Ile Leu
195 200 205
Ala Glu Ile Ser Gln Thr Lys Val Ile Asp Pro Leu Asn Glu Leu Ser
210 215 220
Cys Ser Leu Lys Asp Tyr Tyr Ile Tyr Lys Lys Asn Glu Ala Tyr Leu
225 230 235 240
Val Glu Lys Leu Pro Asp Cys Thr Pro Val Val Tyr Val Lys Ser Lys
245 250 255
Ser Gly Gly Asn Met Leu Ser Tyr Tyr Pro Gln Ala Leu Ile Pro Val
260 265 270
Leu Thr Arg Glu Lys Val Gly Ile Leu Ala Pro Asp Phe Ser Thr Arg
275 280 285
Ile Glu Pro Val Val Lys Arg Ser Met Ala Asn Arg Ile Ile Leu Asp
290 295 300
Lys Glu Phe Ile Thr Asp Ile Gly Asn Ile Asp Asn Leu Asn Gly Leu
305 310 315 320
Ala Phe Glu Ile Asp Thr Thr Asn Leu Asp Ser Leu Gly Leu Ala Ala
325 330 335
Thr Thr Val Ser Met Pro Gln Leu Met Cys Gly Asp Gly Lys Phe Ile
340 345 350
Asn Cys Gly Asn Glu Tyr Gln Ile Phe Asn His Gly Phe Tyr Gln Lys
355 360 365
Pro Asn Arg Lys Leu Arg Ile Gly Tyr Leu Tyr Pro Arg Gly Glu Lys
370 375 380
Glu Leu Leu Val Gln Val Ala Asn Asp Ile Tyr Ser Tyr Ala Met Leu
385 390 395 400
Gly Lys Tyr His Gly Glu Thr Asp Asn Tyr Ile Ile Pro Gly Leu Ile
405 410 415
Asp Ile Gln Thr Gln Pro Glu Ile Thr Gln Glu Tyr Asp Val Gly Asn
420 425 430
Ile Thr Asp Tyr Lys Arg Ala Ala Leu Lys Leu Lys Asn Ile Glu Gln
435 440 445
Ile Asp Ile Val Ile Ala Leu Ile Pro Asp Gly Leu Asp Glu Asp Ser
450 455 460
Pro Tyr Asn Pro Phe Lys Lys Ile Trp Ala Glu Leu Asn Ile Pro Ser
465 470 475 480
Gln Met Ile Ser Met Lys Thr Ala Arg Lys Phe Cys Ser Asp Ala Lys
485 490 495
Ser Lys Gly Thr Ser Ser Lys Tyr Tyr Leu Gln Asn Ile Val Leu Gly
500 505 510
Ile Leu Gly Lys Thr Gly Gly Ile Pro Trp Ile Val Lys Asn Met Pro
515 520 525
Gly Asn Val Asp Cys Phe Val Gly Leu Asp Val Ser Thr Gln Ala Lys
530 535 540
Gly Ile His Tyr Pro Thr Cys Ser Val Val Phe Asp Arg Tyr Gly Arg
545 550 555 560
Met Leu Gly Phe Phe Lys Pro Arg Val Ala Gln Gln Gly Glu Lys Ile
565 570 575
Thr Thr Gln Ile Leu Gln Asp Val Phe Asp Gln Val Ile Leu Ser Tyr
580 585 590
Glu Asn Glu Tyr Gly Glu Lys Pro Lys Asn Ile Val Ile His Arg Asp
595 600 605
Gly Phe Ser Asn Glu Asp Lys Glu Trp Tyr Glu His Tyr Phe Lys Ala
610 615 620
Gln Gly Ile Asn Tyr Ala Ile Ile Glu Val Arg Lys Asn Ile Tyr Lys
625 630 635 640
Lys Met Leu Asp Ile Asp Thr Ser Asp Met Asn Pro Ser Ala Gly Ser
645 650 655
Cys Ile Tyr Asn Ser Asn Lys Ala Tyr Leu Val Thr Thr Val Met Lys
660 665 670
Gly Arg Lys Gly Ser Pro Asn Pro Leu Leu Ile Glu Lys Ala Cys Gly
675 680 685
Asn Ile Ser Ile Gly Glu Ala Val Thr Gln Ile Leu Tyr Leu Thr Gln
690 695 700
Leu His Val Gly Ser Thr Gln Lys Met Arg Leu Pro Ile Thr Thr Gly
705 710 715 720
Tyr Ala Asp Lys Ile Cys Lys Asn Leu Asp Asn Val Pro Thr Gly Gln
725 730 735
Val Glu Asn Lys Leu Phe Phe Leu
740
<210> 54
<211> 742
<212> PRT
<213> artificial sequence
<400> 54
Met Ser Lys Asp Leu Lys Met Glu Ile Phe Ala Ser Lys Glu Thr Val
1 5 10 15
Lys Pro Val Thr Phe His Val Tyr Glu Phe His Thr Ser Glu Leu Tyr
20 25 30
Glu Asn Lys Phe Lys Leu Ile Arg Ser Ala Val Trp Lys Ile Lys Asn
35 40 45
Val Asn Thr Cys Gly Val Phe Glu Asp Gly Lys Tyr Ile Tyr Thr Thr
50 55 60
Glu Lys Ile Glu Glu Asn Ile Pro Asn Thr Asp Phe Lys Leu Val Tyr
65 70 75 80
Leu Gly Glu Lys Val Leu Glu Val Leu Glu Asn Lys Lys Val Tyr Ser
85 90 95
Glu Leu Ile Arg Tyr Tyr Ile Val Glu Asn Leu Lys Lys Ile Lys Ile
100 105 110
Tyr Asp Gln Tyr Arg Lys Tyr Ala Cys Arg Ser Asn Ile Thr Ser Arg
115 120 125
Trp Ile Met Thr Glu Lys Gly Phe Gln Thr Phe Ser Ser Arg Asp Lys
130 135 140
Gln Ile Ser Leu Glu Arg Lys Tyr Asn Val Ala Val Tyr Ile Gln Asp
145 150 155 160
Asn Gly Lys Ala Tyr Leu Lys Ile Asp Thr Ser Ser Ile Phe Ser Ser
165 170 175
Asn Gln Thr Val Ala Asp Leu Ile Asp Gln Gly Ile Asp Pro Arg Gly
180 185 190
Met Glu Val Lys Asn Glu Trp Ala Lys Asn Phe Gln Val Gly Ile Leu
195 200 205
Lys Glu Ile Cys Asn Tyr Thr Val Thr Asp Lys Ile Asp Phe Ala Asp
210 215 220
Ser Leu Lys Ala Tyr Tyr Val Asp Thr Lys Lys Glu Ser Tyr Arg Val
225 230 235 240
Glu Asn Leu Pro Asp Asp Thr Leu Val Val Thr Val Glu Leu Gln Pro
245 250 255
Gly Lys Asn Tyr Pro Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr
260 265 270
Arg Glu Lys Val Gly Gln Ile Asp Pro Ala Phe Ser Leu Ser Ile Glu
275 280 285
Arg Tyr Val Lys Arg Asp Met Ala Leu Arg Ile Glu Leu Asp Lys Asn
290 295 300
Phe Ile Gln Asp Ile Gly Lys Ile Thr Gln Ile Gly Asn Leu Glu Phe
305 310 315 320
Glu Gln Glu Met Cys Gln Val Ala Asp Leu Gly Tyr Lys Arg Gly Thr
325 330 335
Ile Gln Leu Pro Val Leu Thr Cys Gly Arg Asn Arg Glu Leu Arg Cys
340 345 350
Gly Glu Glu Phe Lys Val Phe Asn Tyr Gly Phe Tyr Tyr Lys Pro Glu
355 360 365
Lys Lys Ile Lys Ile Gly Tyr Ile Tyr Pro Lys Asn Gln Ile Asn Leu
370 375 380
Met Lys Ala Val Ala Asn Ala Ile Cys Asp Phe Ala Ala Asn Gly Arg
385 390 395 400
Tyr His Gly Glu Lys Asp Ala Tyr Ile Val Glu Gly Leu Leu Asp Ile
405 410 415
Gln Met Lys Pro Ile Ala Ile Glu Glu Tyr Ala Leu Asn Asp Ile Thr
420 425 430
Asp Tyr Lys Arg Ala Ala Asn His Leu Arg Lys Ile Glu Asp Met Asp
435 440 445
Ile Val Ile Gly Ile Val Pro Asp Glu Met Asp Asp Asp Gly Pro Tyr
450 455 460
Asn Pro Phe Lys Ser Ile Trp Ala Glu Val Asn Ile Pro Ser Gln Met
465 470 475 480
Val Ser Val Lys Thr Ala Arg Leu Phe Glu Arg Gly Lys Ala Glu Gly
485 490 495
Asn Lys Thr Lys Tyr Tyr Leu His Asn Ile Leu Leu Gly Ile Leu Gly
500 505 510
Lys Ala Gly Gly Ile Pro Trp Ile Ile Lys Glu Met Pro Gly Asn Val
515 520 525
Asp Cys Phe Val Gly Leu Asp Val Ala Thr Val Glu Lys Gly Ile His
530 535 540
Phe Pro Ala Cys Ser Val Val Phe Asp Lys Gln Gly Arg Leu Leu Gly
545 550 555 560
Phe Tyr Lys Pro Lys Ser Ala Gln Arg Gly Glu Lys Ile Thr Thr Lys
565 570 575
Ile Leu Arg Asp Ile Phe Asp Gln Val Ile Phe Ser Tyr Glu Asp Lys
580 585 590
Phe Gly Asp Lys Pro Lys Ser Ile Met Ile His Arg Asp Gly Phe Ser
595 600 605
Asn Glu Asn Asp Glu Trp Tyr Gln Glu Tyr Phe Gly Glu Lys Glu Ile
610 615 620
Ala Tyr Thr Ile Val Glu Val Arg Lys Asn Ile Ser Ser Lys Leu Val
625 630 635 640
Leu Ile Glu Asp Gly Glu Ile Lys Asn Pro Thr Thr Gly Tyr Cys Val
645 650 655
Tyr Asn Lys Glu Lys Ala Tyr Leu Val Thr Thr Asn Met Lys Asn Lys
660 665 670
Lys Gly Ser Pro Asn Pro Leu Leu Ile Glu Lys Lys Cys Gly Asn Ile
675 680 685
Ser Met Gly Asp Val Leu Lys Gln Val Leu Tyr Leu Ser Gln Leu His
690 695 700
Val Gly Ser Thr Gln Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala
705 710 715 720
Asp Lys Ile Cys Lys Asn Arg Glu Phe Val Pro Glu Gly Lys Met Asn
725 730 735
Gln Arg Leu Phe Phe Leu
740
<210> 55
<211> 740
<212> PRT
<213> artificial sequence
<400> 55
Met Gly Lys Asp Leu Arg Met Glu Val Phe Ala Ser Lys Asp Ala Val
1 5 10 15
Lys Pro Val Ser Leu His Ile Tyr Gln Leu His Ser Gln Lys Ile Asp
20 25 30
Asn Ser Phe Ser Val Ile Arg Gly Ala Val Trp Lys Leu Arg Asn Tyr
35 40 45
Asn His Ile Gly Val Phe Glu Asp Gly Asn Arg Ile Tyr Ser Thr Asp
50 55 60
Met Leu Asp Glu Cys Ile Pro Asn Ala Asp Phe Thr Ile Glu Tyr Glu
65 70 75 80
Gly Ile Arg Glu Ile Glu Val Leu Glu Asn Arg Lys Val Tyr Cys Glu
85 90 95
Leu Ile Lys Tyr Leu Ile Thr Lys Asn Leu Ser Glu Ile Leu Ile Tyr
100 105 110
Asn Lys Tyr His Lys Tyr Ser Cys Lys Ser Ser Val Thr Ser Lys Trp
115 120 125
Ile Lys Thr Asp Asn Asp Phe Lys Leu Phe Thr Ser Asp Asn Lys Glu
130 135 140
Ile Ser Leu Glu Arg Lys Tyr Asn Phe Trp Val Asp Ile Met Asp Asp
145 150 155 160
Gly Lys Ala Tyr Leu Arg Ile Asp Thr Ser Ser Ala Phe Thr Ser Asn
165 170 175
Leu Thr Val Tyr Asp Tyr Met Glu Arg Gly Ile Asn Pro Val Gly Met
180 185 190
Glu Val Lys Asn Asp Trp Ala Lys Asn Asn Gln Thr Gly Ile Leu Thr
195 200 205
Glu Ile Cys Asp Phe Thr Val Thr Asp Lys Leu Asp Phe Ala Asp Ser
210 215 220
Leu Lys Ala Tyr Tyr Ile Asn Lys Lys Glu Gly Lys Arg Val Glu Gln
225 230 235 240
Leu Pro Asp Asp Thr Lys Val Val Lys Val Glu Leu Gln Ser Asp Lys
245 250 255
Thr Tyr Pro Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr Arg Glu
260 265 270
Lys Val Gly Gln Ile Asp Pro Arg Phe Ser Val Arg Ile Glu Pro Tyr
275 280 285
Val Lys Arg Asp Met Arg Thr Arg Leu Met Leu Asp Gln Asn Phe Ile
290 295 300
Gly Asp Ile Gly Val Leu Lys Glu Ile Asn Ser Leu Gln Phe Asp Leu
305 310 315 320
Glu Pro Cys Glu Val Lys Asn Ile Gly Tyr Ser Arg Gly Thr Val Pro
325 330 335
Leu Pro Lys Leu Ile Cys Gly Lys Asp Arg Val Leu Glu Val Gly Lys
340 345 350
Glu Phe Gln Val Phe Asn Tyr Gly Phe Tyr Arg Lys Pro Asp Arg Glu
355 360 365
Ile Lys Ile Gly Tyr Leu Tyr Pro Lys Asn Gln Glu Asn Leu Met Lys
370 375 380
Ala Val Val Asn Glu Ile Tyr Ser Phe Ala Lys Leu Gly Lys Tyr Gln
385 390 395 400
Gly Glu Lys Asp Lys Tyr Ile Ile Ser Gly Leu Leu Asn Ile Lys Ser
405 410 415
Glu Pro Met Ile Lys Glu Glu Tyr Glu Leu Gly Asp Ile Thr Asp Tyr
420 425 430
Lys Arg Ala Ala Asn Arg Leu Gln Lys Ile Glu Gly Ile Asp Ile Val
435 440 445
Ile Ala Leu Ile Pro Asp Gly Ile Asp Glu Asp Gly Pro Tyr Asn Pro
450 455 460
Phe Lys Ala Ile Trp Ala Lys Ala Asn Ile Pro Ser Gln Met Ile Ser
465 470 475 480
Val Lys Thr Ala Glu Leu Phe Ala Arg Gly Lys Ala Glu Gly Asn Lys
485 490 495
Ser Lys Tyr Tyr Leu His Asn Ile Val Leu Gly Ile Leu Gly Lys Thr
500 505 510
Gly Gly Ile Pro Trp Ile Val Lys Asp Met Pro Gly Asn Val Asp Cys
515 520 525
Phe Val Gly Leu Asp Val Ala Thr Val Ala Lys Gly Ile His Tyr Pro
530 535 540
Ala Cys Ser Val Val Phe Asp Lys Tyr Gly Arg Leu Leu Gly Phe Tyr
545 550 555 560
Lys Pro Thr Thr Pro Gln Gln Gly Glu Lys Ile Thr Thr Arg Ile Leu
565 570 575
Gln Asp Ile Phe Asp Gln Val Ile Phe Ser Tyr Glu Asp Lys Phe Gly
580 585 590
Glu Ser Pro Lys Asn Val Val Ile His Arg Asp Gly Phe Ser Asn Glu
595 600 605
Asn Asp Asp Trp Tyr Lys Asn Tyr Phe Gly Ala Lys Gly Ile Glu Tyr
610 615 620
Ser Ile Ile Glu Val Arg Lys Asn Ile Ser Ser Lys Leu Ile Leu Leu
625 630 635 640
Gln Asp Asp Asn Ile Glu Asn Pro Thr Met Gly Tyr Cys Val Tyr Asn
645 650 655
Asp Ser Lys Gly Tyr Leu Val Thr Thr Asp Met Lys Asn Lys Lys Gly
660 665 670
Ser Pro Asn Pro Ile Leu Val Glu Lys Lys Cys Gly Asn Ile Ser Met
675 680 685
Ala Asp Val Leu Thr Gln Ile Leu Tyr Leu Ser Gln Leu His Val Gly
690 695 700
Ser Thr His Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp Lys
705 710 715 720
Ile Cys Lys Asn Arg Asp Phe Val Pro Glu Gly Lys Met Asp Asp Arg
725 730 735
Leu Phe Phe Leu
740
<210> 56
<211> 745
<212> PRT
<213> artificial sequence
<400> 56
Met Gly Lys Leu Thr Val Glu Ala Phe Glu Gly Ile Gly Glu Leu Thr
1 5 10 15
Pro Met Thr Phe Asn Gln Tyr Arg Leu Ile Gly Lys Gly Lys Ile Asp
20 25 30
Asn Val Tyr Gln Val Ile Asn Lys Ala Lys Tyr Ala Met His Ser Ser
35 40 45
Asn Tyr Phe Lys Pro Val Phe Ile Lys Asp Asp Met Leu Tyr Thr Leu
50 55 60
Glu Glu Phe Lys Thr Ile Pro Asn Leu Asp Glu Val Asp Ile Lys Leu
65 70 75 80
Asn Lys Ser Glu Val Leu Asn Ile Glu Asp Asn Thr Asp Ile Tyr Ser
85 90 95
Lys Val Val Glu Tyr Tyr Ile Asn Phe Met Leu Gly Lys Val Lys Val
100 105 110
Leu Glu Lys Tyr Lys Lys Tyr Lys Thr Gln Asn Thr Asp Glu Ile Ile
115 120 125
Ser Asn Thr Ile Leu Thr Arg Asn Leu Arg Asp Glu Phe Lys Lys Ser
130 135 140
Glu Lys Gly Phe Met Leu Lys Arg Lys Phe Lys Ile Lys Pro Val Val
145 150 155 160
Asn Lys Glu Gly Asn Val Ile Leu Tyr Leu Ser Cys Ser Ser Asp Phe
165 170 175
Ser Thr Asn Lys Asn Ile Tyr Gln Met Ile Asn Glu Gly Leu Asp Val
180 185 190
Ile Gly Leu Pro Val Lys Asn Ile Trp Asn Asn Ile Arg Gly Asn Ala
195 200 205
Val Ile Gln Glu Ile Ser Asp Lys Lys Ile His Glu Pro Thr Thr Phe
210 215 220
Gly Gln Ser Leu Ile Asp Tyr Tyr Val Thr Arg Asn Gln Gly Lys Arg
225 230 235 240
Val Glu Gly Phe Thr Glu Glu Asp Lys Asn Ala Asn Val Ile Lys Val
245 250 255
Lys Thr Asn Lys Ile Val Leu Asp Cys Ile Pro His Ala Leu Ala Pro
260 265 270
Ile Ile Thr Arg Glu Tyr Leu Cys Gln Asn Asp Pro Lys Phe Ser Asn
275 280 285
Asp Ile Glu Lys Leu Ile Lys Met Asp Met Asn Tyr Arg Tyr Asn Thr
290 295 300
Leu Lys Ala Phe Ile Asp Asp Ile Gly Ile Ile Lys Glu Leu Asn Asn
305 310 315 320
Leu Ser Phe Lys Lys Glu Tyr Tyr Asp Asp Ile Lys Leu Leu Gly Tyr
325 330 335
Ser Ser Gly Thr Leu Asn Glu Pro Gln Leu Ile Gly Ala Lys Gly Val
340 345 350
Ile Lys Asn Lys Ile Asn Ile Phe Thr Asn Gly Phe Tyr Lys Met Pro
355 360 365
Lys Glu Gln Val Lys Phe Gly Val Ile Phe Pro Glu Gly Tyr Glu Glu
370 375 380
Ala Ser Lys Lys Thr Met Arg Ala Ile Tyr Asp Phe Val Asn Asp Gly
385 390 395 400
Lys Tyr His Gln Glu Lys Asn Arg Tyr Ile Ala Asp His Leu Met Asn
405 410 415
Met Cys Phe Lys Thr Asp Glu Cys Ile Phe Glu Ser Tyr Lys Leu Gly
420 425 430
Asp Ile Thr Glu Tyr Lys Lys Thr Ala Leu Lys Leu Lys Asn Tyr His
435 440 445
Asn Ile Lys Phe Val Ile Ala Ile Ile Pro Asn Ala Cys Glu Asp Asp
450 455 460
Ile Glu Asn Pro Tyr Asn Pro Phe Lys Lys Ile Trp Ala Glu Leu Asn
465 470 475 480
Leu Pro Ser Gln Met Ile Ser Leu Lys Thr Ala Glu Met Phe Lys Val
485 490 495
Ser Lys Asp Gln Thr Ala Leu Tyr Tyr Leu His Asn Ile Ser Leu Gly
500 505 510
Ile Leu Gly Lys Ile Gly Gly Ile Pro Trp Val Val Lys Asp Met Gln
515 520 525
Gly Asp Val Asp Cys Phe Ile Gly Leu Asp Val Gly Thr Arg Glu Lys
530 535 540
Gly Ile His Tyr Pro Ala Cys Ser Val Val Phe Asp Lys Phe Gly Lys
545 550 555 560
Leu Ile Asn Tyr Tyr Lys Pro Asn Val Pro Gln Ser Gly Glu Ile Ile
565 570 575
Gln Thr Asn Ile Leu Gln Glu Ile Phe Asp Asn Ile Leu Ile Ser Tyr
580 585 590
Glu Glu Glu Asn Gly Thr Tyr Pro Lys Asn Ile Ile Ile His Arg Asp
595 600 605
Gly Phe Ser Arg Glu Asp Leu Ser Trp Tyr Glu Asn Tyr Phe Asn Asn
610 615 620
Lys Gly Ile Lys Phe Asn Ile Ile Glu Val Arg Lys Asn Thr Pro Leu
625 630 635 640
Lys Ile Ala Glu Ile Asp Asn Lys Lys Val Ser Asn Pro Pro Ile Gly
645 650 655
Ser Tyr Ile Met Lys Gly Asn Lys Ser Phe Ile Val Thr Thr Asp Ile
660 665 670
Lys Glu Asn Leu Gly Ser Pro Lys Pro Leu Lys Ile Glu Lys Thr Tyr
675 680 685
Gly Asp Ile Asp Met Leu Thr Val Leu Asn Gln Ile Tyr Ala Leu Thr
690 695 700
Gln Ile His Val Gly Ser Pro Lys Ser Leu Arg Leu Pro Ile Thr Thr
705 710 715 720
Gly Tyr Ala Asp Lys Ile Cys Lys Ala Ile Glu Phe Ile Pro Gln Gly
725 730 735
Val Leu Asp Asn Arg Leu Phe Phe Leu
740 745
<210> 57
<211> 710
<212> PRT
<213> artificial sequence
<400> 57
Met Asn His Tyr Tyr Phe Ser Glu Cys Lys Ala Asp Glu Lys Ala Ser
1 5 10 15
Asp Ile Ala Ile His Leu Tyr Thr Val Pro Leu Ser Asn Pro His Glu
20 25 30
Lys Tyr Ser Tyr Ala His Ser Ile Ala Tyr Glu Leu Arg Lys Leu Asn
35 40 45
Ser Tyr Ile Thr Val Ala Ala His Gly Gln Tyr Ile Ala Ser Phe Glu
50 55 60
Glu Ile Cys His Trp Gly Asp His Arg Tyr Ile Gln His Glu His Arg
65 70 75 80
Pro Ile Gln Cys Ser Leu Pro Met Glu Arg Thr Ile Leu Glu Arg Leu
85 90 95
Leu Lys Lys Glu Leu Glu Asn Arg Cys Lys Ser Ser Tyr Lys Met Asp
100 105 110
Asn Asp Leu Phe Arg Leu Ala Asn Glu Gln Ser Met His Val Gly Glu
115 120 125
Ile Ser Ile His Pro Ala Ile Tyr Ile Ser Phe Ser Val Glu Glu Asn
130 135 140
Gly Asp Ile Phe Val Gly Phe Asp Tyr Gln His Arg Phe Glu Tyr Arg
145 150 155 160
Lys Thr Leu Gln Asp Val Ile Asn Asn Asp Pro Ser Leu Leu Lys Glu
165 170 175
Gly Met Glu Val Val Asp Pro Phe Asn Arg Arg Ala Tyr Tyr Tyr Thr
180 185 190
Phe Val Gly Met Ala Asp Tyr Thr Ala Gly Gln Lys Ser Pro Phe Leu
195 200 205
Gln Gln Ser Val Ile Asp Tyr Tyr Leu Glu Lys Asn Glu Leu Trp Lys
210 215 220
Leu Lys Gly Val His Glu Lys Thr Pro Val Val His Val Lys Ser Arg
225 230 235 240
Asp Gly His Leu Leu Pro Tyr Leu Pro His Leu Leu Lys Leu Thr Cys
245 250 255
Ser Tyr Glu Gln Leu Leu Pro Ser Met Thr Lys Glu Val Asn Arg Leu
260 265 270
Ile Lys Leu Ser Pro Asn Glu Lys Met Ser Lys Leu Tyr Thr Glu Met
275 280 285
Phe Arg Leu Leu Arg Gln Gln Gln Val Leu Thr Phe Lys Lys Glu Asn
290 295 300
Val Arg Ala Val Asn Leu Gly Tyr Asp Val Asn Glu Leu Asp Ser Pro
305 310 315 320
Ile Met Glu Phe Gly Gln Gly Tyr Lys Thr Asn Glu Ile Tyr Arg Gly
325 330 335
Leu Lys Gln Ser Gly Val Tyr Glu Pro Ser Ser Val Ala Val Ser Phe
340 345 350
Phe Val Asp Pro Glu Leu Asn Tyr Asp Pro Gln Lys Arg Lys Glu Val
355 360 365
Gly Cys Phe Val Lys Lys Leu Glu Ser Met Ser Glu Ala Leu Gly Val
370 375 380
Lys Leu Asn Ile Ser Asp Gln Pro Arg Gln Leu Tyr Gly Gln Leu Pro
385 390 395 400
Lys Asp Phe Phe Met Gln Asp Asn Leu Ser Tyr His Leu Lys Ser Ile
405 410 415
Thr Asp Gln Phe Arg Gly Thr Val Val Val Val Ile Gly Thr Glu Glu
420 425 430
Asn Ile Asp Arg Ala Tyr Val Thr Ile Lys Lys Glu Phe Gly Gly Lys
435 440 445
Glu Asp Leu Met Thr Gln Phe Val Gly Phe Thr Ser Ser Leu Val Thr
450 455 460
Glu Asn Asn Ile Phe His Tyr Tyr Asn Ile Leu Leu Gly Ile Tyr Ala
465 470 475 480
Lys Ala Gly Val Gln Pro Trp Ile Leu Ala Ser Pro Met His Ser Asp
485 490 495
Cys Phe Ile Gly Leu Asp Val Ser His Glu His Gly Lys His Ala Ser
500 505 510
Gly Ile Ile Gln Val Ile Gly Arg Asp Gly Lys Ile Ile Lys Gln Lys
515 520 525
Ser Val Ala Thr Ala Glu Ala Gly Glu Thr Ile Ala Asn Ser Thr Met
530 535 540
Glu Glu Ile Val Asn Glu Ser Ile Tyr Ser Tyr Glu Gln Ile Tyr Gly
545 550 555 560
Ala Lys Pro Arg His Ile Thr Phe His Arg Asp Gly Ile Cys Arg Glu
565 570 575
Asp Leu Asp Phe Leu Gln Ala Tyr Leu Arg Ser Phe Gln Ile Pro Phe
580 585 590
Asp Phe Val Glu Ile Ile Lys Lys Pro Arg Arg Arg Met Ala Ile Tyr
595 600 605
Ser Asn Lys Lys Trp Val Thr Lys Gln Gly Ile Tyr Tyr Ser Lys Gly
610 615 620
Asn Thr Ala Tyr Leu Cys Ala Thr Asp Pro Arg Glu Ser Val Gly Met
625 630 635 640
Ala Gln Leu Val Lys Ile Val Gln Lys Thr Asn Gly Leu Ser Val His
645 650 655
Glu Ile Val Ser Asp Val Tyr Lys Leu Ser Phe Met His Ile His Ser
660 665 670
Met Leu Lys Thr Arg Leu Pro Ile Thr Ile His Tyr Ser Asp Leu Ser
675 680 685
Ser Thr Phe His Asn Arg Gly Leu Ile His Pro Arg Ser Gln His Glu
690 695 700
Arg Ala Leu Pro Phe Val
705 710
<210> 58
<211> 712
<212> PRT
<213> artificial sequence
<400> 58
Met Ser Ser Tyr Phe Phe Ser Glu Trp Leu Leu Asp Thr Arg Thr Glu
1 5 10 15
Glu Ile Pro Phe His Trp Tyr Thr Val Pro Leu Lys Asn Leu Gly Glu
20 25 30
Ala Glu Val Glu Ala Glu Thr Ala Thr Ile Val Arg Gln Leu Arg Arg
35 40 45
Asn His Pro Gly Trp Ala Ile Ala Ser Ala Gly His Leu Ile Gly Ala
50 55 60
Phe Gln Pro Val Ala Ser Asp Glu Ile Gln Leu Gln Gly Glu Gln Lys
65 70 75 80
Arg Asp Ile Asn Pro Ser Ile Pro Leu Glu Arg Arg Leu Leu Glu Arg
85 90 95
Leu Leu Ser Arg Ser Phe Glu Leu Ser Gln Asn Arg Ala Asp Tyr Arg
100 105 110
Ala Ser Tyr Gly Lys Val Ile Pro Arg Lys Pro Thr Gln Val Val Gly
115 120 125
Gly Ile Glu Ile Arg Arg Tyr Leu Gln Phe Asp Met Asn Val Asp Glu
130 135 140
Ser Gly Arg Ile Thr Val Gly Phe Glu Leu Ser His Gln Tyr Ser His
145 150 155 160
Val Gln Asn Ile Glu Glu Met Leu Arg Arg Ala Pro Gly Lys Ile Glu
165 170 175
Pro Lys Cys Leu Val Val Asn Arg Val Asp His Gln Thr Tyr Trp Tyr
180 185 190
Val Arg Gln Leu Glu Ser Ser Ile Val Asp Pro Ile Leu Pro Asn Gly
195 200 205
Gln Ser Leu Lys Glu Tyr His Ile Ala Asn Gly Arg Glu Ser Trp Val
210 215 220
His Ser Leu Pro Asp His Thr Pro Ala Val Glu Cys Leu Asn His Lys
225 230 235 240
Asp Lys Pro Leu Ser Phe Val Pro Gln Phe Leu Lys Leu Val Ser Ser
245 250 255
Phe Asp Gln Val Pro Ala Pro Ala Gln Lys Val Ser Lys Leu Ala Pro
260 265 270
Ser Lys Arg Val Gln Thr Met Phe Leu Thr Ala Glu Asp His Leu Gln
275 280 285
Gln Trp Lys Gln Lys Ala Glu Phe Pro Leu Ser Phe Asp Arg Trp Gly
290 295 300
Leu Asp Ala Lys Lys Lys Gly Tyr Val Pro Leu Thr Leu Thr Asp Pro
305 310 315 320
Leu Leu Val Phe Gly Lys Gly Arg Lys Asp Arg Asn Pro Tyr Arg Gly
325 330 335
Leu Ser Ala Gly Gly Ile His Glu Thr Pro Lys Ser Ser Leu Ala Cys
340 345 350
Gln Tyr Leu Leu Asp Asp Asp Ile Leu Arg Lys Val Leu Ala Gly Glu
355 360 365
Lys Gly Lys Arg Ile Leu Pro Ile Glu Lys Glu Leu Ser Lys Arg Ser
370 375 380
Ala Gln Leu Gly Val Pro Leu Thr Leu Lys Gly Pro Val His Arg Ile
385 390 395 400
Gln Phe Ser Asp Ser Gln Asn Thr Arg Val Lys Leu Met Glu Leu Ser
405 410 415
Glu Gln Val Ala Pro Gly Cys Pro Leu Ile Val Val Ala Asp Arg Lys
420 425 430
Asn Leu Ser Lys Gly Leu Tyr Gly Leu Leu Lys Gln Val Leu Gly Lys
435 440 445
Asp Tyr Ala Val Ser Thr Gln Val Val Thr Met Asp Thr Leu Glu Leu
450 455 460
Gln Lys Gly Arg Ser Thr Ala Leu Leu Asn Leu Leu Leu Gly Val Tyr
465 470 475 480
Val Lys Ser Gly Ile Gln Pro Trp Val Leu Ser Glu Pro Leu Tyr Ser
485 490 495
Pro Cys Phe Ile Gly Leu Asp Val Ser Arg Glu Asp Gly Lys His Gly
500 505 510
Ala Gly Val Val Gln Thr Ile Gly Thr Asp Gly Arg Val Leu Trp Ser
515 520 525
Lys Pro Val Thr Ser Val Glu Ala Gly Glu Lys Ile Gly Pro Glu Thr
530 535 540
Leu Glu Lys Ile Val Ala Glu Thr Val Phe Arg Phe Arg Lys Arg Tyr
545 550 555 560
Arg Arg Val Pro Asp His Ile Thr Phe His Arg Asp Gly Lys Gly His
565 570 575
Trp Glu Glu Ile Glu Ala Leu Asn Arg Ile Ala Glu Ser His Gly Ile
580 585 590
Lys Phe Asp Tyr Ile Ser Leu Val Lys Lys Ala Gly Arg Arg Met Ala
595 600 605
Met Arg Glu Glu Lys Gln Gly Ala Trp Lys Asn Pro Met Gly Val Ala
610 615 620
Leu Leu Lys Gly Asp Thr Ala Tyr Leu Cys Ala Thr Asp Pro Ala Asp
625 630 635 640
Phe Leu Gly Met Ala Gln Pro Val Arg Ile Gln Gln Arg Thr Gly Thr
645 650 655
Leu Lys Met Glu Glu Ile Val Glu Asp Ile Phe Lys Leu Ser Tyr Met
660 665 670
Asn Val His Ala Ile Asn Lys Ser Arg Leu Pro Val Thr Val Asn Tyr
675 680 685
Ala Asp Lys Ser Ser Thr Phe Phe Asn Arg Gly Met Leu Pro Thr His
690 695 700
Val Glu Met Pro Val Gln Ser Val
705 710
<210> 59
<211> 705
<212> PRT
<213> artificial sequence
<400> 59
Met Glu Gln Phe Phe Leu Ser Glu Leu Phe Leu Asp Thr Arg Ser Asn
1 5 10 15
Gln Ile Pro Leu Tyr Phe Tyr His Val Pro Val Leu Asp Leu Glu Lys
20 25 30
Ile Asp Gln Tyr His Tyr Lys Thr Leu Arg Leu Leu Glu Lys Gln Asn
35 40 45
Pro Asp Gln Thr Ile His Phe Tyr Arg His Leu Ile Gly Ser Phe His
50 55 60
Pro Ile Lys Tyr Trp Gly Glu Met Gly Asp Gln Thr Leu Val His Arg
65 70 75 80
Pro Ile Lys Thr Asn Ile Ile Glu Glu Arg Lys Leu Leu Glu Arg Leu
85 90 95
Leu Ile Lys Asn Ile Glu Gln Ala Gln Asn Arg Asp His Phe Tyr Thr
100 105 110
Tyr Arg Gly Arg Ile Thr Lys Lys Lys Pro Glu Thr Ser Ser Thr Ile
115 120 125
Leu Ser Phe Arg Tyr Leu Thr Leu His Thr Thr Ile Asp His Thr Ser
130 135 140
Arg Ile Ser Ile Gly Phe Asn Met Gly His Thr Leu Leu His Lys Met
145 150 155 160
Asn Leu Tyr Gln Leu Leu Gln Glu Lys Thr Asn Ile Leu His Glu Gly
165 170 175
Met Glu Val Phe Asp Pro Tyr Asn Arg Ser Thr Tyr Lys Phe Ile Gly
180 185 190
Gln Ser Gln Ala Thr Val Ser Asp Pro Ile Leu Pro Gly Asn Gln Ser
195 200 205
Ile Leu Glu Tyr Leu Arg Gln Gln Gly Arg Thr Asn Leu Lys Ile Pro
210 215 220
Gln Asn Thr Pro Ala Val Thr Val Glu Ser Lys Gly Arg Ser Lys Lys
225 230 235 240
Gln Phe His Phe Ala Pro Gln Leu Leu Lys Leu Ile Cys Ser Phe Asp
245 250 255
Gln Val Ser Ile Pro Gln Gln Ile Gln Gln Gln Ile Lys Leu Asn Ala
260 265 270
His Lys Arg Thr Glu Met Met Arg Lys Phe Val Glu His Val Leu Ser
275 280 285
Asn Trp Gln Asn Lys Ala Pro Phe Pro Val Ser Phe Ser Met Asn Ser
290 295 300
Thr Gln Pro Lys Gln His Gly Tyr His Ile Lys Gln Phe Lys Asp Pro
305 310 315 320
Phe Leu Leu Phe Gly Arg Gly Phe Thr Thr Gln Asp Gln Lys Asn Gly
325 330 335
Leu Lys Gln Gly Gly Ser Tyr Thr Arg Pro Ala Gln Lys Val Lys Tyr
340 345 350
Gln Tyr Leu Ile Gln Pro Glu Ile Ile Asp Arg Leu Val Asn Gln Lys
355 360 365
Asn His Phe Gln Phe Ala Lys Ser Leu Glu Gln Gln Ser Ser Lys Trp
370 375 380
Gly Val Glu Leu Asp Ile His Lys Thr Gly Arg Lys Glu Leu Asp Phe
385 390 395 400
Ser Asn Ser Thr Lys Leu Arg Asp Ser Leu Lys Glu Ile Ala Pro Thr
405 410 415
Leu Gln Tyr Pro Thr Val Val Ile Ile Asp Glu Gln Tyr Arg Thr Asn
420 425 430
Lys Ala Ile Tyr Arg Ile Ile Lys Gln Glu Cys Gly Arg Glu Lys Asn
435 440 445
Ile Pro Thr Gln Val Val Tyr Leu Asp Thr Thr His Asn Lys Tyr Ala
450 455 460
Tyr Ala Asn Ile Leu Leu Gly Leu Tyr Ala Lys Ala Gly Ile Gln Pro
465 470 475 480
Trp Ile Leu Lys Lys Pro Leu His Ser Pro Cys Phe Ile Gly Leu Asp
485 490 495
Val Ser Arg Asp Asp Gly Lys His Ser Thr Gly Val Val Gln Ala Val
500 505 510
Gly Gln Asp Gly Arg Ile Leu Phe Ala Gln Ser Leu Thr Ser Thr Glu
515 520 525
Arg Gly Glu Ile Ile Ser Glu Asp Ser Leu Gln Gln Ile Ile Ser Thr
530 535 540
Ile Arg Tyr His Tyr Asn Lys Glu Phe Gly His Asn Pro Pro His Ile
545 550 555 560
Thr Phe His Arg Asp Gly Arg Gly Tyr Glu Gly Glu Leu Arg Ala Ile
565 570 575
Thr Arg Val Met Asn Glu Met Gly Ile Pro Phe Asp Tyr Ile Ser Val
580 585 590
Val Lys Asn Cys Gln Arg Arg Met Ala Leu Tyr Asn Glu Lys Gln Gly
595 600 605
Lys Tyr Arg Asn Ala Leu Gly Tyr Thr Tyr Ile Lys Asp Asn Phe Ala
610 615 620
Tyr Leu Cys Thr Thr Asn Pro Arg Asp Ala Leu Gly Met Ala Arg Pro
625 630 635 640
Ile Lys Ile Glu Gln Gln Tyr Gly His Leu Thr Met Asp Gln Val Leu
645 650 655
Glu Asp Ile Tyr His Leu Thr Phe Met Asn Thr His Ser Thr Leu Arg
660 665 670
Pro Arg Leu Pro Val Thr Val Asn Tyr Ala Asp Lys Ser Ser Thr Tyr
675 680 685
Tyr Asn Arg Gly Leu Leu Pro Leu Gly Glu Ser Asn Gly Leu Pro Phe
690 695 700
Val
705
<210> 60
<211> 730
<212> PRT
<213> artificial sequence
<400> 60
Met Glu Ser Phe Leu Ile Thr Glu Leu Met Phe Ile Thr Gln Ser Ser
1 5 10 15
Asp Leu Pro Ile His Ile Leu Glu Pro Tyr Pro Arg Glu Phe Ala Lys
20 25 30
Ser His Thr Glu Asn Tyr Glu Val Cys Lys Asp Leu Arg Gln Arg Asn
35 40 45
Asn Asn Arg Val Ile Val Phe Tyr Glu Asn Leu Ile Ala Ser Phe Asp
50 55 60
Glu Ile Lys Tyr Lys Asp Asp Ser Leu Phe Gln Ser Val Glu Tyr Arg
65 70 75 80
Thr Ile His Leu Asp Ser His Ile Glu Arg Glu Leu Leu Ser Arg Leu
85 90 95
Ile Leu Gln Glu Ile Gly His Leu Ala Ser Gln Ser Lys His Ile Ser
100 105 110
Tyr Gly Gln Arg Cys Phe Thr Phe Leu Glu Pro Ile Cys Asp Glu Lys
115 120 125
Thr Gly Glu Ile Ile Thr Asp Asn Asn Gly Thr Leu Val Tyr Pro Lys
130 135 140
Leu Thr Val Asp Cys Arg Val Asp His Asp Gly Lys Ile Tyr Phe Gly
145 150 155 160
Phe Asp Leu Ala His Ser Phe Gln Ser Lys Glu Thr Leu Leu Asp Tyr
165 170 175
Leu Asn Lys Asn Lys Asp Leu Pro Glu Asn Ser Asn Val Ile Asp Ile
180 185 190
Tyr Gly Asn Tyr Arg Tyr Ala Phe Gln Arg Phe Gly Pro Gln Thr Leu
195 200 205
Ser Asp Pro Asn Pro Thr Pro Arg Met Lys Glu Ser Val Lys Ala Tyr
210 215 220
His Glu Arg Leu Asn Val Ser Trp Lys Leu Arg Gly Ile Thr Asn Val
225 230 235 240
Pro Val Ala Phe Val Lys Thr Glu His Asp Glu Glu Leu Ala Tyr Ala
245 250 255
Pro Gln Cys Leu Arg Val Glu Met Pro Phe Ser Lys Ile Lys Ser Lys
260 265 270
Lys Leu Arg Asp Thr Cys Lys Leu Gly Pro Asp Ala Lys Ile Asn Lys
275 280 285
Ala Leu Ser Leu Ala Lys Arg Ile Leu Ser Tyr Ser Pro Arg Tyr Glu
290 295 300
Arg Arg Phe Ser Gly Leu Lys Val Gln Lys Gln Gly Tyr Glu Tyr Thr
305 310 315 320
Thr Trp Ala Pro Pro Asn Leu Arg Phe Arg Asn Gly Ser Ser Ile Asn
325 330 335
Ile Lys Asn Gly Leu Lys Lys Tyr Lys Val Val Ser Lys Val Asp Lys
340 345 350
Pro Val Thr Phe Ser Val Leu Met Asp Lys His Leu Ile Glu Gln Leu
355 360 365
Lys Gln Phe Arg Gln Ile Asn Thr Phe Thr Asp Ile Leu Asn Glu Met
370 375 380
Cys Asp Leu Ser Ser Gln Trp Gly Val Pro Leu Lys Ser Val Arg Leu
385 390 395 400
Asn Ile Ser Asn Ile Cys Phe Glu Leu Pro Asp Lys Leu Ser Tyr Glu
405 410 415
Leu Lys Ala Leu Ser Asp Glu Lys Lys Thr Leu Ile Gln Ser Gln Asp
420 425 430
Ile Leu Leu Val Val Gly Pro Lys Glu Asp Met Glu Ser Glu Asn Ser
435 440 445
Tyr Tyr Ser Val Ile Lys Gln Glu Phe Gly Gln Ser Asn Val Leu Thr
450 455 460
Gln Val Val Leu Leu Glu Asn Leu Lys Leu Gln Glu Pro Lys Asn Arg
465 470 475 480
Leu Phe Ile Leu Glu Asn Leu Val Leu Gly Ile Tyr Ala Lys Cys Gly
485 490 495
Ile Gln Pro Trp Leu Leu Asp Gln Pro Leu His Ser Asp Met Phe Ile
500 505 510
Gly Leu Asp Val Ser His Ile Asn Lys Lys His Ala Ser Gly Cys Ile
515 520 525
Gln Val Met Gly Cys Asp Gly Arg Phe Leu Asn Ser Lys Pro Tyr Glu
530 535 540
Gly Lys Glu Ser Gly Glu Ile Ile Ser Arg Glu Thr Leu Ser Gln Ile
545 550 555 560
Ile Asn Gln Ala Ile Val Ala Tyr Thr Lys His Tyr Pro Asp Lys Pro
565 570 575
Leu Lys His Ile Thr Phe His Arg Asp Gly Lys Pro Leu Gln Lys Glu
580 585 590
Val Asp Ala Ile Arg Ser Ile Leu Gln Gln His Gly Ile Glu Phe Asp
595 600 605
Tyr Val Ser Ile Ile Lys Asn Thr Asn Arg Arg Met Ala Phe Arg Gly
610 615 620
Ile Asn Pro Asn Thr Asn Asn Glu Glu Trp Met Thr Ser Glu Gly Leu
625 630 635 640
Val Tyr Met Lys Asp Asn Tyr Ala Tyr Leu Cys Ser Thr Asn Pro Ser
645 650 655
Thr Ser Val Gly Met Ala Asp Pro Ile Lys Val Glu Lys Tyr Val Gly
660 665 670
Ser Arg Ser Ile Glu Gln Ile Thr Lys Asp Ile Phe Tyr Leu Ser Phe
675 680 685
Met Asn Ile His Ser Met Arg Lys Ser Arg Leu Pro Ala Thr Thr Asn
690 695 700
Tyr Ala Asp Met Ser Ser Lys Phe Tyr Asn Lys Asn Trp Leu Pro Leu
705 710 715 720
Leu Pro Ala Asp Asn Ser Leu Pro Phe Val
725 730
<210> 61
<211> 740
<212> PRT
<213> artificial sequence
<400> 61
Met Glu Lys Asp Leu Lys Leu Glu Val Tyr Ala Ser Lys Thr Lys Val
1 5 10 15
Met Pro Val Ser Leu His Val Tyr Lys Leu Val Ser Gln Asn Ile Thr
20 25 30
Asp Ser Arg Phe Lys Val Ile Arg Gly Ala Ser Trp Lys Ile Arg Asn
35 40 45
Leu Asn Gln Cys Gly Val Phe Glu Asn Gly Glu Val Ile Phe Thr Thr
50 55 60
Glu Glu Ile Glu Thr Glu Ile Pro Lys Ala Asp Phe Lys Leu Glu Tyr
65 70 75 80
Leu Gly Leu Lys Gln Pro Asp Val Gln Glu Asn Lys Arg Val Tyr Glu
85 90 95
Ala Leu Val Lys Tyr Tyr Ile Glu Arg Asn Leu Glu Lys Ile Leu Val
100 105 110
Ala Asp Lys Tyr Arg Lys Tyr Ser Cys Lys Ser Glu Ile Thr Ser Lys
115 120 125
Phe Ile Met Thr Glu Arg Gly Phe Asn Ile Val Thr Ser Gly Asn Lys
130 135 140
Glu Ile Ser Leu Glu Arg Lys Tyr Lys Val Trp Val Ser Ile Glu Glu
145 150 155 160
Asp Gly Tyr Ala Tyr Leu Arg Leu Asp Thr Ser Ser Val Phe Ser Ser
165 170 175
Asn Leu Thr Leu Ala Asp Tyr Ile Ser Lys Gly Lys Asn Val Leu Gly
180 185 190
Met Glu Val Lys Asn Asp Trp Ser Lys Asn Lys Gln Ser Gly Thr Val
195 200 205
Val Glu Val Ser Asp Thr Thr Val Thr Asp Pro Leu Asp Phe Ala Pro
210 215 220
Ser Leu Lys Ala Tyr Tyr Glu Gly Arg Gly Glu Gly Tyr Arg Val Ala
225 230 235 240
Ala Phe Pro Asp Asp Thr Pro Val Val Arg Val Arg Leu Asn Glu Lys
245 250 255
Asn Val Ile Pro Tyr Tyr Pro Gln Ala Leu Lys Pro Ile Leu Ser Arg
260 265 270
Glu Val Val Gly Arg Met Asp Ala Asp Phe Ser Leu Lys Ile Glu Arg
275 280 285
Tyr Val Lys Arg Asp Met Arg Ser Arg Leu Glu Leu Asp Arg Asp Phe
290 295 300
Ile Asn Asp Ile Gly Glu Leu Ser Glu Met Tyr Gly Leu Ala Phe Glu
305 310 315 320
Thr Glu Cys Cys Pro Val Glu Arg Ile Gly Phe Leu Arg Gly Val Val
325 330 335
Glu Met Pro Lys Leu Val Cys Gly Asp Ser Lys Thr Ile Asp Cys Gly
340 345 350
Lys Glu Tyr Gln Val Phe Asn His Gly Phe Tyr Lys Lys Thr Glu Lys
355 360 365
Gln Ile Lys Ile Gly Tyr Leu Tyr Pro Val Gly Thr Lys Pro Leu Met
370 375 380
Lys Ala Ile Val Asn Ala Ile Tyr Gly Phe Ser Val Lys Gly Gln Phe
385 390 395 400
His Gly Glu Lys Asp Lys Tyr Ile Cys Asn Gly Leu Leu Asp Ile Gln
405 410 415
Val Ala Pro Met Ile Gln Glu Glu Tyr Glu Leu Gly Asp Ile Thr Ala
420 425 430
Tyr Lys Arg Ala Ala His Lys Ile Arg Lys Val Glu Asp Ile Asp Ile
435 440 445
Val Ile Ala Met Val Pro Asp Gly Met Glu Glu Asp Ser Pro Tyr Asn
450 455 460
Pro Phe Lys Thr Ile Trp Ala Glu Ala Asn Ile Pro Ser Gln Met Ile
465 470 475 480
Ser Val Ser Thr Ala Arg Leu Phe Ala Asn Glu Thr Asp Ser Asn Ser
485 490 495
Ser Arg Tyr Phe Leu His Asn Ile Val Leu Gly Ile Leu Gly Lys Thr
500 505 510
Gly Gly Ile Pro Trp Ile Val Lys Asp Met Pro Gly Asn Ala Asp Cys
515 520 525
Phe Val Gly Leu Asp Val Ala Thr Val Asp Ala Gly Ile His Phe Pro
530 535 540
Ala Cys Ser Val Leu Phe Asp Lys Tyr Gly Lys Leu Ile Gly Phe Tyr
545 550 555 560
Lys Pro Lys Gln Ala Gln Lys Gly Glu Lys Ile Thr Thr Lys Ile Leu
565 570 575
Gln Asp Ile Phe Asp Gln Val Leu Phe Ser Tyr Glu Asp Glu Tyr Gly
580 585 590
Glu Pro Pro Lys Ser Ile Val Ile His Arg Asp Gly Phe Ser Asn Glu
595 600 605
Asn Asp Asp Trp Tyr Glu Lys Tyr Phe Ser Leu Lys Gly Ile Ala Tyr
610 615 620
Thr Ile Val Glu Val Arg Lys Asn Ile Ser Ser Lys Ile Val Met Tyr
625 630 635 640
Lys Asp Gly Glu Val Thr Asn Pro Asp Ile Gly Tyr Cys Val Tyr Asn
645 650 655
Gln Ser Gln Ala Tyr Leu Val Thr Thr Asp Met Lys Gln Lys Lys Gly
660 665 670
Ser Pro Asn Pro Ile Leu Ile Glu Lys Arg Cys Gly Asp Glu Lys Met
675 680 685
Ile Asp Val Ile Arg Gln Ile Leu Phe Leu Thr Gln Leu His Val Gly
690 695 700
Ser Thr His Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp Lys
705 710 715 720
Ile Cys Lys Asn Arg Glu Phe Val Pro Glu Gly Lys Val Asp Asn Lys
725 730 735
Leu Phe Phe Leu
740
<210> 62
<211> 714
<212> PRT
<213> artificial sequence
<400> 62
Met Lys Arg Ser Ile Leu Thr Glu Trp Gln Met Thr Ser Lys Ala Glu
1 5 10 15
Asp Phe Pro Leu His Met Tyr Arg Phe Pro Val Arg Asp Trp Asp Gln
20 25 30
Lys Tyr Gln Gly Thr Tyr Pro Ile Val Ser Arg Leu Arg Arg Leu Asn
35 40 45
Asp Trp Gln Ala Met Ala Phe His Glu Ser Val Ile Ala Ser Phe Asp
50 55 60
Pro Ile Gln Lys Trp Glu Glu Asp Ser Pro Asn His Tyr Glu Glu Arg
65 70 75 80
Pro Ile His Val Glu Ser Arg Phe Glu Arg Glu Leu Leu Gln Arg Val
85 90 95
Leu Leu Lys Ser Leu Glu Ala Ala Gln Pro Lys Gly Lys Tyr Arg Ile
100 105 110
Arg Tyr Gly Gln Phe Val Ser Lys His Pro Ser Phe Arg Ile Gln Gly
115 120 125
Ile Gly Val His Pro Ala Leu Thr Leu Gln Ile Asn Val Asp Glu Thr
130 135 140
Gly Val Ile Arg Val Gly Phe His Leu Ser His Arg Phe Ile Pro Glu
145 150 155 160
Lys His Leu Gly Glu Leu Leu Lys Glu Gly Ser Pro Leu Ile Met Glu
165 170 175
Gly Val Thr Val Val Asp Pro Tyr His Gln Tyr Ser Tyr Arg Phe Ile
180 185 190
Glu Glu Asp Glu Arg Thr Val Gly Ser Phe Phe Lys Glu Val Glu Gln
195 200 205
Pro Leu Ile Gln Tyr Tyr Gln Asn Lys Ser Gln Gly Phe Arg Val Lys
210 215 220
Asp Val Ser Pro Asp Thr Lys Ala Val Lys Val Lys Gly Lys Lys Lys
225 230 235 240
Glu Pro Leu Pro Phe Ile Pro Asp Leu Leu Met Leu Glu Ala Ser Tyr
245 250 255
Lys Gln Leu Pro His Gln Ile Leu Lys Pro Val Ser Lys Glu Ile Lys
260 265 270
Leu Ser Ser His Val Lys Thr Glu Arg Met Leu Glu Met Val Glu Ala
275 280 285
Ile Leu Gln His Phe Pro Arg Leu Ser Tyr Asp Lys Ser Gly Leu Leu
290 295 300
Ala Ser Lys Gln Gly Tyr Gln Leu Val Lys Leu Lys Lys Pro Leu Leu
305 310 315 320
Arg Phe Gly Asn Arg His Thr Asn Pro Leu Pro Phe Tyr Gly Leu Lys
325 330 335
Lys Gly Gly Val Tyr Arg Asn Glu Ile Asp Arg Leu Gln Val Thr Tyr
340 345 350
Phe Val Asp Gly Asp Leu Val Asn Arg Ile Gln Gln Gln Ala Ser Ala
355 360 365
Lys Asp His Pro Val Pro Ser Phe Ile Arg Glu Leu Glu Glu Val Ser
370 375 380
Arg Arg Met Gly Val Glu Leu Glu Thr Ile Lys Val Pro Ser Leu Arg
385 390 395 400
Asp Val Val Phe His Asp Pro Gln Glu Leu Lys Lys His Leu Lys Lys
405 410 415
Val Asn Ser Gln Leu Arg Gln Leu Thr Val Val Ile Leu Glu Glu Asp
420 425 430
Arg Ala Asp Ala Cys Tyr Glu Val Ile Lys Gln Glu Leu Thr Gly Lys
435 440 445
Lys Ala Ile Ala Thr Gln Val Ile Thr Leu Lys Thr Val Asp Ile Lys
450 455 460
Asn Gln Lys Ala Arg Glu Tyr Ala Phe Tyr Asn Ile Leu Leu Gly Ile
465 470 475 480
Tyr Gly Lys Ser Gly Arg Val Gln Pro Trp Val Leu Ala Gln Pro Leu
485 490 495
His Ser Asp Cys Phe Ile Gly Leu Asp Val Ser His Lys Asp Gly Lys
500 505 510
His Arg Ser Gly Ile Val Gln Ile Ile Gly Lys Asp Gly Arg Met Leu
515 520 525
Thr Thr Lys Pro Ile Gln Ala Val Glu Lys Gly Glu Lys Ile Ser Lys
530 535 540
Glu Thr Tyr Leu Asp Leu Ile Phe Glu Ala Leu His Arg Tyr Glu Glu
545 550 555 560
Glu Phe Gly Ser Lys Pro Glu His Val Thr Phe His Arg Asp Gly Arg
565 570 575
Gly Leu Pro Glu Glu Met Ala Cys Val Lys Glu Ile Met Ala Gln Glu
580 585 590
Gln Val Ser Tyr Asp Phe Leu Cys Val Ile Lys Asn Pro Gln Arg Arg
595 600 605
Met Ala Tyr Phe Gly Glu Asp Gln Arg Trp Thr Thr Ile Gln Gly Ala
610 615 620
Ala Tyr Ile Arg Glu Lys Arg Ala Tyr Leu Cys Ser Thr Glu Ser Arg
625 630 635 640
Asp Tyr Leu Gly Met Ala Gln Pro Met Arg Leu Glu Arg Glu Thr Gln
645 650 655
Thr Leu Thr Met Glu Gln Leu Val Ser Asp Val Tyr His Leu Ser Phe
660 665 670
Met His Ile Gly Ala Leu Asn Lys Thr Arg Leu Pro Val Thr Ile His
675 680 685
Tyr Ala Asp Lys Ser Ser Thr Phe Ala Asn Lys Gly Met Leu Pro Met
690 695 700
His Gly Asp Glu Lys Ala Leu Leu Phe Leu
705 710
<210> 63
<211> 705
<212> PRT
<213> artificial sequence
<400> 63
Met Asn Thr Pro Leu Thr His Tyr Val Leu Thr Glu Trp Glu Ser Asp
1 5 10 15
Thr Asn Thr Asn Val Leu Asn Ile His Leu Tyr Thr Leu Pro Val Arg
20 25 30
Asn Val Phe Glu Gln His Thr Glu Asn Gly Asn Ala Ser Phe Asp Leu
35 40 45
Arg Lys Leu Asn Arg Ser Leu Val Ile Asp Phe Phe Asn His Tyr Ile
50 55 60
Ala Ser Trp Gln Pro Ile Glu Asn Trp Gly Glu Tyr Thr Phe Thr Gln
65 70 75 80
Tyr Glu Ile Arg Ser Ile Asn Pro Thr Ile Leu Ala Glu Arg Thr Ile
85 90 95
Leu Glu Arg Leu Leu Leu Arg Thr Ile Glu Ser Val Gln Pro Lys Lys
100 105 110
Glu Ile Ala Ala Gly Ser Arg Lys Phe Thr Trp Leu Lys Ala Glu Lys
115 120 125
Val Val Glu Asn Ile Ser Ile His Arg Val Ile Gln Cys Asp Ile Thr
130 135 140
Val Asp Tyr Thr Gly Lys Ile Thr Ile Gly Phe Asp Leu Asn His Ser
145 150 155 160
Tyr Arg Thr Asn Ala Ser Val Tyr Asp Leu Ile Lys Ser Asn Ala Ile
165 170 175
Phe Lys Gly Asp Arg Val Ile Asp Ile Tyr Asn Asn Leu His Tyr Glu
180 185 190
Phe Val Glu Ile Ser Asn Ser Thr Ile Asn Asp Ala Ile Pro Glu Leu
195 200 205
Asn Gln Ser Val Val Ser Tyr Phe Thr Lys Glu Arg Lys Gln Ala Trp
210 215 220
Lys Val Asp Lys Leu Glu Gln Ser Met Pro Val Val Tyr Leu Lys Ala
225 230 235 240
Phe Asn Gly Thr Arg Ile Ala Tyr Ala Pro Ala Met Leu Gln Lys Glu
245 250 255
Leu Thr Phe Glu Ser Leu Pro Ser Ser Val Val Arg Gln Thr Ser Glu
260 265 270
Ile Tyr Lys Gln Asn Ala Asn Gln Lys Ile Lys Thr Leu Leu Asp Glu
275 280 285
Ile Gln Lys Ile Leu Ala Arg Thr Asp Lys Ile Lys Phe Asn Arg Gln
290 295 300
Lys Leu Leu Val Gln Gln Ala Gly Tyr Glu Ile Leu Glu Leu Ser Asn
305 310 315 320
Pro Thr Leu Gln Phe Gly Lys Asn Val Thr Gln Thr Gln Leu Lys Tyr
325 330 335
Gly Leu Asp Lys Gly Gly Val Val Ala Ser Lys Pro Leu Ser Val Asn
340 345 350
Leu Leu Val Tyr Pro Glu Leu Ile Asp Thr Lys Leu Asp Val Ile Thr
355 360 365
Asp Phe Asn Asp Lys Leu Asn Thr Leu Ser His Lys Trp Gly Val Pro
370 375 380
Leu Ser Ile Leu Lys Lys Ser Gly Ala Tyr Arg Asn Lys Ser Ile Asp
385 390 395 400
Phe Thr Asn Pro His Gln Leu Ala Ile Leu Leu Lys Glu Leu Thr Lys
405 410 415
Asn Ser Phe Gln Glu Leu Thr Leu Val Ile Ile Pro Glu Lys Ile Ser
420 425 430
Gly Met Trp Tyr Asp Thr Val Lys Lys Glu Phe Gly Gly Asn Ser Ser
435 440 445
Val Pro Thr Gln Phe Ile Thr Met Glu Thr Leu Gln Lys Ala Asn Asp
450 455 460
Tyr Ile Leu Gly Asn Ile Leu Leu Gly Leu Tyr Ser Lys Ser Gly Ile
465 470 475 480
Gln Pro Trp Ile Leu Asn Ser Phe Leu Ser Ser Asp Cys Phe Ile Gly
485 490 495
Leu Asp Val Ser His Glu Ala Gly Arg His Ser Thr Gly Ile Val Gln
500 505 510
Ile Val Gly Lys Asp Gly Arg Val Leu Ser Ser Arg Ala Asn Thr Ser
515 520 525
Asn Glu Ala Gly Glu Lys Ile Arg His Glu Thr Met Cys Gln Ile Val
530 535 540
Tyr Ser Ala Ile Asp Gln Tyr His Gln His Tyr Asn Glu Arg Pro Lys
545 550 555 560
His Ile Thr Phe His Arg Asp Gly Phe Cys Arg Glu Asp Leu Asp Ser
565 570 575
Leu Asp Glu Val Met Asn Ser Leu Gly Val Glu Tyr Asp Met Val Glu
580 585 590
Ile Ile Lys Lys Thr Asn Arg Arg Met Ala Leu Asn Val Asp Lys Gln
595 600 605
Gly Trp Glu Thr Lys Pro Gly Leu Cys Tyr Val Arg Asp Asp Leu Ala
610 615 620
Tyr Leu Ile Ala Thr Asn Pro His Pro Arg Val Gly Thr Ala Gln Pro
625 630 635 640
Ile Lys Ile Ile Lys Lys Lys Gly Ser Leu Pro Ile Glu Thr Ile Ile
645 650 655
Gln Asp Ile Tyr His Leu Ser Phe Met His Ile Gly Ser Leu Leu Lys
660 665 670
Cys Arg Leu Pro Val Thr Thr Tyr Tyr Ala Asp Leu Ser Ser Thr Phe
675 680 685
Phe Asn Arg Gln Trp Leu Pro Leu Asp Ser Gly Lys Ser Leu His Phe
690 695 700
Val
705
<210> 64
<211> 677
<212> PRT
<213> artificial sequence
<400> 64
Met Pro Val Arg Asn Val Phe Glu Gln His Asn Glu Asn Gly Gln Ala
1 5 10 15
Cys Ser Ala Leu Arg Arg Leu Asn Lys Thr His Val Ile Asp Phe Tyr
20 25 30
Glu Gln Phe Ile Ala Ser Trp Glu Pro Ile Lys Asp Trp Gly Asp Tyr
35 40 45
Thr Phe Thr Asn His Glu Cys Arg Pro Ile Asn Pro Ser Ile Pro Thr
50 55 60
Glu Arg Thr Ile Leu Glu Arg Leu Ile Leu Arg Lys Leu Glu Asn Val
65 70 75 80
Gln Pro Arg Asn Glu Ile Ala Ala Gly Ser Arg Lys Phe Thr Trp Leu
85 90 95
Lys Ala Glu Lys Val Val Gln Gly Val Ser Ile His Arg Val Ile Gln
100 105 110
Val Asp Val Thr Ile Asn Ile Arg Gly Thr Ile Thr Ile Gly Phe Asp
115 120 125
Leu Asn His Ser Phe Arg Thr Asn Glu Ser Ile Tyr Asp Leu Met Lys
130 135 140
Ser Asn Ala Ile Val Ile Gly Glu Arg Val Val Asp Lys Tyr Asn Asn
145 150 155 160
Leu His Tyr Gln Leu Glu Glu Val Ser Glu Ala Thr Ile Ser Asp Val
165 170 175
Ile Pro Glu Leu Asn Gln Ser Val Ile Asp Tyr Phe Val Lys Glu Arg
180 185 190
Lys Gln Ala Trp Lys Val Glu Lys Leu Asp Pro Lys Met Pro Val Val
195 200 205
Tyr Leu Lys Met Asn Asn Gly Leu Arg Ala Ala Tyr Ala Pro Ala Met
210 215 220
Leu Gln Lys Glu Leu Thr Phe Glu Ser Leu Pro Thr Ala Val Val Arg
225 230 235 240
Gln Thr Ser Asp Val Tyr Lys Gln Asn Ala Asn Gln Lys Ile Lys Ile
245 250 255
Leu Leu Glu Glu Ile Gln Lys Ile Leu Ala Arg Asn Asp Lys Leu Thr
260 265 270
Phe Ser Lys Ser Lys Met Leu Val Gln Gln Asn Gly Tyr Asp Val Lys
275 280 285
Gln Leu Leu Asn Pro Asn Leu Ala Phe Gly Lys Gly Ile Ile Gln Ser
290 295 300
Gln Leu Lys Ser Gly Leu Asp Lys Gly Gly Val Val Ala Pro Gln Pro
305 310 315 320
Leu Ser Ile Asn Leu Leu Val Tyr Pro Glu Leu Ile Asp Met Lys Leu
325 330 335
Asp Ala Ile Thr Ala Phe Asn Glu Lys Leu Ser Ala Leu Ser Tyr Lys
340 345 350
Trp Gly Val Pro Leu Ser Ile Met Lys Lys Ser Gly Ala Tyr Arg Asn
355 360 365
Lys Thr Ile Asp Phe Thr Asn Pro His Gln Phe Ala Val Leu Leu Lys
370 375 380
Glu Leu Thr Lys Ser Ser Phe Gln Glu Leu Thr Leu Val Ile Ile Thr
385 390 395 400
Glu Lys Ile Ala Gly Met Trp Tyr Asp Ala Ile Lys Lys Glu Phe Gly
405 410 415
Gly Asn Ala Ala Val Pro Thr Gln Phe Ile Thr Met Glu Thr Leu Gln
420 425 430
Lys Ala Asp Asp Tyr Val Ile Gly Asn Leu Leu Leu Gly Leu Tyr Ser
435 440 445
Lys Ser Gly Ile Gln Pro Trp Val Leu Ser Ser Ser Leu Ser Ser Asp
450 455 460
Cys Phe Ile Gly Leu Asp Val Ser His Glu Ala Gly Arg His Ser Ala
465 470 475 480
Gly Ile Val Gln Val Val Gly Lys Asp Gly Arg Val Leu Ser Ser Arg
485 490 495
Ala Ser Thr Ser Ser Glu Ala Gly Glu Lys Ile Arg His Glu Thr Met
500 505 510
Cys Gln Ile Val Tyr Ser Ala Leu Asp Gln Tyr Gln Ser His Tyr Asn
515 520 525
Glu Lys Pro Arg His Ile Thr Phe His Arg Asp Gly Phe Cys Arg Glu
530 535 540
Asp Leu Asn Ser Leu Asp Glu Val Met Asn Ser Leu Asp Val Gly Tyr
545 550 555 560
Asp Met Val Glu Ile Ile Lys Lys Thr Asn Arg Arg Met Ala Leu His
565 570 575
Val Asp Lys Gln Gly Trp Glu Thr Lys Ser Gly Leu Cys Tyr Val Lys
580 585 590
Asp Asn Leu Ala Tyr Leu Ile Ala Thr Asn Pro His Pro Arg Val Gly
595 600 605
Thr Ala Gln Pro Ile Lys Ile Val Lys Lys Lys Gly Ser Leu Pro Met
610 615 620
Glu Ala Ile Ile Gln Asp Ile Tyr Asn Leu Ser Phe Met His Ile Gly
625 630 635 640
Ser Leu Leu Lys Ser Arg Leu Pro Ile Thr Thr His Tyr Ala Asp Leu
645 650 655
Ser Ser Thr Phe Phe Asn Arg Gln Trp Leu Pro Ile Asp Ser Gly Asp
660 665 670
Ala Leu His Phe Val
675
<210> 65
<211> 713
<212> PRT
<213> artificial sequence
<400> 65
Met Lys Arg Ser Ile Leu Thr Asn Trp Arg Met Lys Ser Thr Thr Glu
1 5 10 15
Asp Phe Pro Leu His Leu Tyr Trp Met Pro Val Arg Asp Trp Asp Asn
20 25 30
Lys Tyr Ala Glu Asn Tyr Ser Val Leu Ser Asp Leu Arg Arg Leu Asn
35 40 45
Gly Trp Gln Pro Met Asp Phe Arg Gly Gln Val Ile Ala Ser Phe Glu
50 55 60
Pro Ile Arg Glu Trp Gly Glu His Ala Tyr Ser Asn Val Glu Val Arg
65 70 75 80
Pro Ile Arg Lys Glu Asp Ala His Glu Arg Ala Val Leu Glu Gln Val
85 90 95
Leu Met Arg Asn Ile Glu Ala Ala Gln Pro Lys Arg Lys Tyr Arg Ile
100 105 110
Arg Asn Gly Gln Phe Thr Met Ala Lys Pro Gly Phe Glu His Ser Gly
115 120 125
Ile Arg Val His Pro Thr Phe Cys Leu Arg Thr Glu Val Asp Lys Thr
130 135 140
Gly Ser Ile Leu Ile Gly Phe His Leu Thr His Arg Phe Leu His Arg
145 150 155 160
Lys His Leu Gly Glu Leu Ile Arg Ser Gly Ser Ser Met Val Arg Glu
165 170 175
Gly Val Thr Val Val Asp Arg Tyr Arg His Thr Arg Tyr Arg Phe Ile
180 185 190
Arg Val Asp Glu Arg Leu Val Gly Gln Pro Phe Gln Glu Ile Arg Arg
195 200 205
Ser Leu Ile Asp Tyr Tyr Ile Asn Arg Asn Gln Gly Phe Leu Val Glu
210 215 220
Lys Val Ser Pro Glu Ser Thr Ala Val Met Val Ala Ala Ser Asn Gly
225 230 235 240
Glu Glu Leu Pro Phe Ile Pro Asp Leu Leu Thr Leu Glu Thr Ser Phe
245 250 255
Glu Gln Leu Pro Gln Pro Ala Ile Arg Pro Ile Ser Arg His Val Lys
260 265 270
Met Ser Ala His Asp Lys Thr Glu Arg Met Ile Gln Ser Val Glu Glu
275 280 285
Ile Leu Gln Ala Tyr Pro Arg Leu Lys Tyr Glu Arg Asn Gly Leu Leu
290 295 300
Ala Ala Val His Gly Phe Glu Leu Thr Thr Phe Ser Ser Pro Val Leu
305 310 315 320
Arg Phe Gly Gln Asn His Thr Ser Lys Ser Thr Phe Lys Gly Leu Lys
325 330 335
Asn Gly Gly Val Phe Lys Asn Glu Thr Asp Lys Leu Asp Val Thr Tyr
340 345 350
Leu Val Asp Gly Glu Ile Ile Arg Glu Ile Leu Gln Gly Lys Pro Asn
355 360 365
Glu His Gln Val Val Arg Phe Met Asn Glu Leu Glu Asn Gln Ser Phe
370 375 380
Trp Thr Gly Val Asp Ile His Arg Ile Asn Thr Thr Ser Gln Leu Arg
385 390 395 400
Arg Val Ile Phe Gln Asp Pro Thr Glu Leu Arg Lys Ser Leu Lys Arg
405 410 415
Ile Ser Ser Asp Leu His Cys Leu Thr Val Ile Ile Thr Asn Glu Glu
420 425 430
Arg Ala Asp Arg Cys Tyr Glu Ala Ile Lys Gln Glu Leu Thr Gly Lys
435 440 445
Lys Ala Ile Ala Thr Gln Val Val Thr Leu Asn Thr Val Glu Ile Asn
450 455 460
Arg Lys Gly Lys Glu Tyr Ala Phe Phe Asn Leu Leu Leu Gly Ile Tyr
465 470 475 480
Gly Lys Ser Gly Val Ile Gln Pro Trp Val Leu Ala Gln Ser Leu His
485 490 495
Ser Asp Cys Phe Ile Gly Leu Asp Val Ser His Asp Asp Gly Lys His
500 505 510
Ala Thr Gly Ile Val Gln Val Val Gly Lys Asp Gly Arg Met Leu Asp
515 520 525
Ser Lys Pro Leu Arg Thr Ile Glu Lys Gly Glu Lys Ile Gly Glu Gly
530 535 540
Thr Tyr Leu Asp Leu Thr Leu Glu Ala Ile His Gln Tyr Glu Glu Thr
545 550 555 560
Phe Gly Glu Arg Pro Glu His Ile Thr Phe His Arg Asp Gly Lys Cys
565 570 575
Tyr Glu Glu Glu Leu Asn His Val Arg Asn Ile Met Gly Asp Glu Gly
580 585 590
Val Lys Phe Asp Tyr Ile Ser Val Ile Lys Asp Ser Gln Thr Arg Ile
595 600 605
Ala Arg Phe Ser Glu Asn Asn Arg Trp Glu Thr Val Leu Gly Ala Ala
610 615 620
Tyr Ile Lys Lys Asp Leu Ala Tyr Leu Cys Ser Thr Asn Pro His Glu
625 630 635 640
Arg Met Gly Met Ala Lys Pro Leu Lys Ile Glu Arg Met Ser Gly Asn
645 650 655
Leu Pro Met Gln Gln Val Val Leu Asp Ile Phe His Leu Ser Tyr Met
660 665 670
His Ile Gly Ala Leu Asn Lys Thr Arg Leu Pro Val Thr Thr His Tyr
675 680 685
Ala Asp Lys Ser Ser Thr Arg Phe Asn Arg Gly Met Leu Pro Ser Tyr
690 695 700
Gly Asp Gly Lys Ala Leu Leu Phe Leu
705 710
<210> 66
<211> 740
<212> PRT
<213> artificial sequence
<400> 66
Met Glu Lys Asp Leu Arg Met Glu Val Phe Ser Ser Lys Asp Ile Val
1 5 10 15
Arg Glu Thr Cys Leu His Val Tyr Gln Leu His Thr Gln Lys Ile Asp
20 25 30
Asn Ala Phe Ser Ile Ile Arg Gly Ala Ala Trp Lys Leu Arg Asn Tyr
35 40 45
Tyr His Val Gly Val Phe Glu Asp Gly Lys Arg Ile Tyr Thr Thr Glu
50 55 60
Lys Ile Glu Gly Asn Val Pro Asn Ala Asp Phe Ser Ile Glu Tyr Glu
65 70 75 80
Gly Leu Gln Glu Leu Pro Val Leu Ser His Arg Lys Ile Tyr Cys Glu
85 90 95
Leu Ile Lys Tyr Leu Ile Thr Gln Asn Leu Ser Lys Val Met Ile Phe
100 105 110
Asp Lys Tyr Arg Lys Tyr Ser Cys Lys Ser Asn Ile Thr Ser Lys Trp
115 120 125
Leu Met Thr Asn Gln Gly Phe Gln Thr Phe Thr Ser Glu Asn Lys Glu
130 135 140
Ile Ser Ile Glu Arg Lys Tyr Asn Phe Trp Val Glu Ile Leu Asp Asn
145 150 155 160
Gly Lys Ala Tyr Leu Arg Leu Asp Thr Gly Ser Val Phe Thr Ser Asn
165 170 175
Leu Thr Val Asn Asp Tyr Leu Ile Arg Gly Val Asp Pro Thr Gly Met
180 185 190
Glu Val Lys Asn Asp Trp Ala Lys Asn Asn Gln Thr Gly Ile Leu Thr
195 200 205
Glu Ile Cys Asp Phe Thr Val Thr Asp Lys Leu Asp Phe Ala Asp Asn
210 215 220
Leu Lys Ala Tyr Tyr Ile Glu Arg Lys Glu Gly Tyr Arg Val Glu Lys
225 230 235 240
Ile Pro Asp Asp Thr Thr Val Val Lys Val Glu Leu Gln Pro Gly Lys
245 250 255
Ser Tyr Pro Tyr Tyr Pro Gln Ala Leu Lys Pro Val Leu Thr Arg Glu
260 265 270
Lys Val Gly Glu Ile Asp Pro Leu Phe Ser Leu Arg Ile Asp Ser Tyr
275 280 285
Val Lys Arg Asp Met Gln Thr Arg Leu Glu Leu Asp Ile Asp Phe Ile
290 295 300
Arg Asp Ile Gly Ala Leu Ser Asp Leu Ala Asn Leu Glu Phe Asn Thr
305 310 315 320
Glu Thr Cys Thr Val Glu Glu Met Glu Tyr Thr Lys Gly Lys Val Pro
325 330 335
Leu Pro Lys Leu Ile Cys Gly Lys Asp Lys Val Ile Glu Cys Gly Lys
340 345 350
Glu Phe Gln Val Phe Asn Tyr Gly Phe Tyr Arg Lys Thr Asp Arg Lys
355 360 365
Ile Arg Ile Gly Tyr Ile Tyr Pro Lys Asn Thr Phe Glu Glu Met Lys
370 375 380
Ala Ile Val Asn Glu Ile Tyr Ser Phe Ala Thr Leu Gly Lys Tyr His
385 390 395 400
Gly Glu Arg Asp Lys Tyr Ile Ile Glu Gly Leu Leu Asp Ile Gln Ala
405 410 415
Glu Pro Met Ile Arg Glu Glu Tyr Glu Ile Gly Asp Leu Thr Asp Tyr
420 425 430
Lys Arg Ala Ala Asn Arg Leu Gln Lys Val Glu Gly Ile Asp Ile Val
435 440 445
Ile Ala Leu Ile Pro Asp Gly Val Asp Glu Asp Gly Pro Tyr Asn Pro
450 455 460
Phe Lys Thr Ile Trp Ala Lys Ala Asn Ile Pro Ser Gln Met Ile Ser
465 470 475 480
Met Lys Thr Ala Glu Leu Phe Ala Arg Gly Lys Ala Glu Gly Asn Lys
485 490 495
Ser Lys Tyr Tyr Leu Gln Asn Ile Ile Leu Gly Ile Leu Gly Lys Thr
500 505 510
Gly Gly Val Pro Trp Ile Val Lys Asp Met Pro Gly Asn Val Asp Cys
515 520 525
Phe Val Gly Leu Asp Val Ala Thr Val Ala Lys Gly Ile His Tyr Pro
530 535 540
Ala Cys Ser Val Val Phe Asp Lys Tyr Gly Arg Leu Leu Gly Phe Tyr
545 550 555 560
Lys Pro Thr Thr Pro Gln Gln Gly Glu Lys Ile Thr Thr Arg Ile Leu
565 570 575
Gln Asp Ile Phe Asp Gln Val Ile Phe Ser Tyr Glu Asp Lys Phe Gly
580 585 590
Glu Arg Pro Lys Asn Val Val Ile His Arg Asp Gly Phe Ser Asn Glu
595 600 605
Asn Asp Asp Trp Tyr Lys Asn Tyr Phe Gly Ala Lys Gly Ile Glu Tyr
610 615 620
Thr Ile Ile Glu Val Arg Lys Asn Ile Ser Ser Lys Leu Ile Leu Leu
625 630 635 640
Gln Asp Asp Lys Val Thr Asn Pro Pro Met Gly Tyr Cys Val Tyr Asn
645 650 655
Asn Asn Arg Gly Tyr Leu Ile Thr Thr Asp Met Lys Asn Lys Lys Gly
660 665 670
Ser Pro Asn Pro Ile Leu Ile Glu Lys Lys Cys Gly Asp Ile Ser Met
675 680 685
Ala His Ile Leu Thr Gln Ile Leu Tyr Leu Ser Gln Leu His Val Gly
690 695 700
Ser Thr His Lys Met Arg Leu Pro Ile Thr Thr Gly Tyr Ala Asp Lys
705 710 715 720
Ile Cys Lys Asn Arg Asp Phe Val Pro Glu Gly Lys Val Asp Asp Arg
725 730 735
Leu Phe Phe Leu
740
<210> 67
<211> 709
<212> PRT
<213> artificial sequence
<400> 67
Met Gly Ser Phe Ile Leu Thr Glu Tyr Lys Ala Ala Ile His Ala Ser
1 5 10 15
Gln Ile Lys Leu His Ile Tyr Arg Met Pro Ile Lys Asp Arg Glu Asn
20 25 30
Ile Asp Arg Glu Tyr Gly Thr His Thr Tyr Gln Leu Arg Gln Lys Asn
35 40 45
Arg Thr Thr Ile Ala Phe Tyr Arg Ser Leu Ile Gly Ser Phe Lys Lys
50 55 60
Leu Thr Asp Glu Pro Asp Gly Tyr Glu His Tyr Glu Tyr Arg Pro Ile
65 70 75 80
Lys Leu Asp Gln Ser Pro Glu Ser His Gln Glu Arg Lys Leu Leu Glu
85 90 95
Arg Leu Ile Leu Arg Gly Leu Gly Asp Ala Ser Arg Lys Glu Phe Phe
100 105 110
Thr Asn Gly Gln Ser Ile Phe Glu Lys Lys Pro Phe Lys Tyr Leu Ser
115 120 125
Glu Cys Lys Ile Tyr Arg Gly Ile His Ile Asp Val Thr Val Lys Glu
130 135 140
His Gly Asp Ile Met Ile Gly Phe Glu Leu Lys His Ser Ile Gln Ser
145 150 155 160
Asn Gln Ser Ile Ser Ala Ala Leu Arg Gln Gln Glu Leu Asn Lys Gly
165 170 175
Asp Lys Val Phe Asp Tyr Ile Asn Asn Ala His Phe Gln Phe Glu Gly
180 185 190
Ile Ser Asp Lys Thr Ile Ser Asp Pro Leu Pro Asp Leu Asn Asn Lys
195 200 205
Ser Ile Leu Gln His Tyr Glu Thr Lys Pro Ser Ile Tyr Asn Ser Leu
210 215 220
Ser Lys Asn Pro Asn Ala Lys Ala Val Leu Val Arg Ser Lys Lys Gly
225 230 235 240
Lys Val Tyr His Tyr Ala Pro Gln Leu Leu Leu Lys Glu Cys Leu Met
245 250 255
Lys Asp Val Pro Pro Lys Glu His Ser Ser Val Lys Leu Asp Pro Ser
260 265 270
Glu Lys Ile Asn His Ser Val Lys Leu Met Glu Lys Ile Ile Lys Ala
275 280 285
Phe Lys Gln Gln Tyr Phe Pro Ile Gly Phe Glu Pro Lys Ser Leu Asn
290 295 300
Ile Gly Lys Ser Gly Tyr Gln Cys His Ser Val Pro Asp Pro Leu Leu
305 310 315 320
Arg Ile Gly Asn Gly Ala Thr Cys Lys His Gln Asn Leu Lys Val Ser
325 330 335
Leu Ser Arg His Lys Ile Phe Asp Ser Ile Ser Ser Pro Val Gln Tyr
340 345 350
Gln Leu Leu Leu Asp Ser Lys Phe His Gln Glu Trp Lys Lys Arg Ile
355 360 365
Ala Glu Gln Phe Lys His Thr Leu Glu Lys Lys Ser Lys Gln Trp Gly
370 375 380
Val Glu Leu Gln Ser Ala Gly Asn Pro Gln Phe Leu Pro Thr Ser Asn
385 390 395 400
Pro Arg Ser Leu Glu Phe Leu Leu Lys Asp Ile Glu Phe Asp Ser Ala
405 410 415
Val Ile Tyr Ala Val Leu Leu Asp Glu Asn Lys Gln Glu Glu Ser Gly
420 425 430
Ile Tyr Ser Val Phe Lys Lys Glu Leu Gly Gly Asn Arg Gly Ile His
435 440 445
Thr Gln Val Ile Leu Ile Asn Ser Leu Lys Asn Glu His Thr Ile Pro
450 455 460
Gln Ile Leu Leu Gly Ile Tyr Thr Lys Ala Gly Leu Gln Pro Trp Ile
465 470 475 480
Leu His Lys Pro Leu His Ala Asp Cys Tyr Val Gly Tyr Asp Val Ser
485 490 495
His Glu Asn Gly Arg His Ala Thr Gly Ile Val Gln Val Phe Gly Lys
500 505 510
Asp Gly Ser Gln Ile Trp Ser Gln Pro Ile Ser Ser Thr Glu Ala Gly
515 520 525
Glu Lys Val Ser Lys Ser Thr Ile Gln Ser Met Val Ile His Val Leu
530 535 540
His Tyr Tyr Gln Arg Lys Met Gly Lys Lys Pro Glu His Ile Val Phe
545 550 555 560
His Arg Asp Gly Thr Gly Tyr Asp Glu Glu Ile Glu Trp Ile Lys Glu
565 570 575
Ile Leu Ser Asp Gln Glu Ile Thr Gly Lys Ser Val Ser Phe Asp Tyr
580 585 590
Val Ser Ile Val Lys Glu Cys Gly Arg Arg Met Ala Tyr Phe Asp Glu
595 600 605
Ile Lys Tyr Lys Met Asn Asn Ile Pro Gly Thr Ala Tyr Ile Asp Ser
610 615 620
Lys Asn Gln Lys Ala Tyr Leu Cys Leu Thr Asp Pro Ile Arg Lys Ile
625 630 635 640
Gly Met Ala Lys Pro Leu Lys Ile Ile Lys His Thr Gly Lys Leu Thr
645 650 655
Leu Glu Gln Ile Ala Glu Asp Val Tyr His Leu Ser Phe Met Asn Ile
660 665 670
His Thr Asp Arg Lys Val Arg Leu Pro Val Thr Thr Asn Tyr Ala Asp
675 680 685
Lys Ser Ser Thr Phe Phe Asn Arg Gly Tyr Leu Ser Ala Gln Lys Glu
690 695 700
Gly Ile Gly Phe Val
705
<210> 68
<211> 739
<212> PRT
<213> artificial sequence
<400> 68
Met Lys Glu Thr His Leu Leu Thr Glu Trp Gln Leu Lys Thr Lys Ser
1 5 10 15
Ser Asp Ile Ser Ile His Leu Tyr Trp Met Pro Gln Lys Tyr Gln Glu
20 25 30
Lys Asp Leu Val Glu Lys Glu Ile Gly Asn Leu Lys Tyr Ser Val Ser
35 40 45
Arg Leu Asn Gly Phe Ile Ile Val Glu Ser Ala Ala His Leu Leu Gly
50 55 60
Ser Phe Glu Glu Ile Lys Ala Trp Gly Asp Val Ile Pro Leu Arg His
65 70 75 80
Glu Tyr Arg Cys Ile Asp Leu Thr Ser Ser Thr Glu Arg Arg Leu Leu
85 90 95
Glu Arg Leu Leu Ser Arg Ser Leu Glu Arg Ala Gln Asp Ala Glu Lys
100 105 110
Phe Asn Ala Arg Arg Arg Thr Ile Val Pro Lys Asn Asp Arg Gln Val
115 120 125
Val Asp Asp Phe Glu Val Arg Arg Thr Leu Glu Phe Asp Ile Thr Val
130 135 140
Ser Ser Lys Gly Arg Ile Ser Val Gly Phe Asp Leu Ser His Glu Phe
145 150 155 160
Thr His Arg Lys Asn Val Tyr Gln Leu Ile Lys Glu Gln Ser Asp Leu
165 170 175
Ile Gly Pro Asn Cys Lys Val Lys Asp Ile Val Tyr Gly Arg Thr Tyr
180 185 190
Phe Phe Lys Glu Val Leu Asp Lys Pro Ile Ser Tyr Pro His Leu Ser
195 200 205
Ser Gly Glu Asn Leu Ile Asp Tyr Tyr Lys Asn Lys Gly Lys Gly Asn
210 215 220
Tyr Val Lys Ser Leu Arg Phe Glu Thr Pro Ala Val Ser Cys Val Ser
225 230 235 240
Lys Glu Gly Ala Glu Pro Leu Pro Phe Ile Pro Gln Leu Leu Lys Ile
245 250 255
Val Cys Ser Trp Asp Lys Val Pro Phe Asp Ala Lys Lys Lys Thr Lys
260 265 270
Met Ser Thr Asn Gln Arg Met Asp Ala Leu Met Asn Met Ile Lys Asp
275 280 285
Ala Leu Gly Ala Trp Lys Gln Asn Ala Ala Tyr Leu Pro Ile Glu Tyr
290 295 300
Asp Lys Arg Gly Leu Leu Ala Asn Glu Thr Gly Tyr Leu Ile Lys Pro
305 310 315 320
Leu Lys Lys Pro Asn Leu Gln Phe Gly Lys Gly Val Lys Gly Ile Ser
325 330 335
Ala Phe Ala Ser Leu Leu Ser Gly Gly Val Val Ser Pro Pro Ser Gln
340 345 350
Pro Ile Glu Cys Gln Phe Leu Val Asp Ala Gln Ile Val Lys Glu Phe
355 360 365
Ile Lys Asp Phe Asn Gly Glu Leu Asp Phe Pro Leu Phe Arg Arg Leu
370 375 380
Ser Tyr Leu Ser Asn Gln Leu Gly Val Pro Met Val Arg Pro Asp Phe
385 390 395 400
Arg Ser Lys Gln Ile Val Leu Ile Arg Phe Asp Asp Pro Val Arg Leu
405 410 415
Arg Met Glu Leu Arg Asn Ile Lys Glu His Met Asn Pro Glu His Pro
420 425 430
Ile Leu Ile Val Gly Lys Lys Glu Asn Leu Lys Lys Lys Thr Gly Pro
435 440 445
Asp Gln Gly Asp Tyr Tyr Thr Leu Leu Lys Arg Glu Leu Gly Arg Glu
450 455 460
His Lys Phe Ser Thr Gln Val Val Thr Phe Glu Thr Ser Glu Tyr Lys
465 470 475 480
Ser Lys Lys Arg Asp Glu Lys Lys Lys Arg Glu Asp Leu Glu Arg Val
485 490 495
Tyr Met Asn Ile Leu Leu Gly Ile Tyr Val Lys Met Gly Ile His Pro
500 505 510
Trp Lys Leu Ser Asp Arg Leu His Ser Asp Cys Phe Ile Gly Leu Asp
515 520 525
Val Cys His Glu Lys Asp Leu His Ile Thr Gly Val Ile Gln Val Ile
530 535 540
Gly Gln Asp Gly Leu Pro Leu Trp Thr Lys Pro Leu Ser Asn Pro Glu
545 550 555 560
Arg Gly Glu Val Ile Arg Arg Glu Thr Ile Glu Asp Thr Ile Tyr Lys
565 570 575
Thr Leu Asp Lys Phe Lys Gln Met Asn Gly Arg Ile Pro Gln His Ile
580 585 590
Thr Phe His Arg Asp Gly His Gly His Lys Asp Glu Leu Lys Val Ile
595 600 605
Arg Glu Leu Leu Glu Pro Leu Gln Ile Lys Phe Asp Tyr Val Ser Ile
610 615 620
Glu Lys Thr Leu Asn Arg Arg Met Ala Tyr Lys Ile Gln Gly Lys Pro
625 630 635 640
Glu Trp Leu Asn Pro Val Gly Phe Ala Tyr Val Lys Asp Gly Glu Arg
645 650 655
Leu Ala Tyr Leu Cys Thr Thr Asn Pro Ser Glu Phe Val Gly Met Ala
660 665 670
Gln Pro Phe Arg Met Ile Gln Trp Thr Asp Ser Leu Lys Phe Asp Leu
675 680 685
Ile Ile Glu Asp Val Tyr Arg Leu Thr Phe Met Asn Ile His Ser Ile
690 695 700
Asn Lys Ser Arg Leu Pro Ser Thr Ile Asn Tyr Ala Asp Lys Ser Ala
705 710 715 720
Ser Phe Phe Ala Arg Gly Met Leu Pro Leu Asp Thr Glu Met Pro Ile
725 730 735
Gln Ser Val
<210> 69
<211> 709
<212> PRT
<213> artificial sequence
<400> 69
Met Asp Asn Tyr Ile Leu Thr Glu Tyr Lys Ala Gly Ile His Ala Ser
1 5 10 15
Glu Ile Lys Ile His Ile Tyr Arg Met Pro Val Lys Asp Leu Glu Lys
20 25 30
Ile Asp Tyr Glu Tyr Gly Lys Tyr Thr Arg Asp Leu Arg Gln Lys Asn
35 40 45
Arg Lys Thr Ile Ser Phe Tyr Arg Ser Leu Ile Gly Ser Phe Glu Lys
50 55 60
Leu Thr Ile Val Pro Lys Gly Tyr Glu Lys Tyr Glu Tyr Arg Ser Ile
65 70 75 80
Lys Leu Asp Gln Ser Glu Glu Ser Leu Gln Glu Arg Lys Leu Leu Glu
85 90 95
Arg Leu Ile Phe Asp Gly Leu Arg Asp Ser Asn Arg Asn His Phe Met
100 105 110
Ser Thr Glu Gln Ser Ile Ile Glu Lys Glu Pro Ile Lys Ser Leu Ser
115 120 125
Lys Cys Lys Ile His Arg Gly Ile Tyr Ile Asp Ile Thr Val Lys Glu
130 135 140
Lys Gly Asp Ile Phe Ile Gly Phe Glu Leu Lys His Ser Ile Gln Ser
145 150 155 160
Thr His Thr Ile Ile Lys Ala Leu Lys Glu Lys Lys Leu Asn Lys Gly
165 170 175
Asp Lys Val Phe Asp Phe Leu Asn Ser Ala His Tyr Glu Phe Glu Gly
180 185 190
Ile Ser Asp Lys Thr Ile Ser Asp Pro Leu Pro Glu Leu Gly Asn Lys
195 200 205
Ser Ile Ile Gln His Tyr Lys Thr Lys Pro Ser Ile Tyr Cys His Leu
210 215 220
Val Lys Lys Pro Asn Met Pro Ala Ile Leu Val Arg Ser Lys Ser Gly
225 230 235 240
Lys Val Tyr Pro Tyr Pro Pro Gln Leu Leu Lys Lys Glu Cys Leu Met
245 250 255
Lys Asp Val Pro Ala Lys Glu His Ser Ser Ile Lys Leu Asn Pro Asn
260 265 270
Asp Lys Ile Asn Tyr Ser Ile Glu Ile Met Lys Arg Ile Ile Asp Ala
275 280 285
Phe Glu Asn Arg Tyr Phe Pro Ile Gly Phe Glu Lys Asn Asn Leu Asn
290 295 300
Ile Ala Lys Leu Gly Tyr Arg Arg Arg Leu Val Pro Asp Pro Leu Leu
305 310 315 320
Arg Ile Gly Asn Gly Ala Thr Cys Asn His Arg Asp Leu Lys Gly Ala
325 330 335
Phe Leu Arg His Lys Ile Tyr Asp Ser Val Ser Ser Pro Ile Tyr Tyr
340 345 350
Gln Leu Leu Leu Asp Gln Pro Phe Glu Arg Glu Trp Gln Lys Lys Met
355 360 365
Ser Glu Ala Phe Ile Thr Lys Met Glu Asn Arg Ser Arg Gln Trp Gly
370 375 380
Ile Lys Leu Gln Cys Thr Gly Asn Gln Ile Leu Pro Thr Ser Asn Pro
385 390 395 400
Tyr Ala Leu Arg Leu His Leu Lys Asp Ile Asn Leu Asp Thr Asp Ile
405 410 415
Ile Ser Val Val Leu Leu Asp Glu Thr Lys Gln Glu Gly Glu Glu Val
420 425 430
Tyr Ser Thr Ile Lys Lys Glu Leu Gly Gly Thr Arg Gly Ala His Thr
435 440 445
Gln Val Ile Leu Ile Asp Ser Leu Lys Asn Glu Tyr Thr Ile Pro Gln
450 455 460
Ile Leu Leu Gly Ile Tyr Thr Lys Ala Gly Leu Gln Pro Trp Val Leu
465 470 475 480
His Gln Pro Leu His Ala Asp Cys Tyr Val Gly Tyr Asp Val Ser His
485 490 495
Glu Asn Gly Arg His Thr Thr Gly Ile Val Gln Val Phe Gly Lys Asp
500 505 510
Gly Ser Gln Ile Phe Ser Gln Pro Ile Ser Ser Ala Glu Ala Gly Glu
515 520 525
Lys Val Ser Lys Glu Thr Ile Gln Thr Met Val Ile His Val Leu Tyr
530 535 540
Tyr Tyr Gln Lys Lys Val Gly Lys Met Pro Gln His Ile Val Phe His
545 550 555 560
Arg Asp Gly Arg Gly Tyr Val Glu Glu Ile Asp Trp Ile Lys Asp Ile
565 570 575
Leu Ser Asn Arg Asp Leu Thr Asn Gly Gln Ser Ile Ala Phe Asp Tyr
580 585 590
Ile Ser Val Ile Lys Glu Cys Gly Arg Arg Met Ala Tyr Phe Asp Asp
595 600 605
Ile Lys Lys Lys Tyr Val Asn Val Pro Gly Ile Ala Tyr Leu Asp Asp
610 615 620
Asn Ala Gln Lys Ala Tyr Leu Cys Ser Thr Asn Pro Tyr Glu Lys Val
625 630 635 640
Gly Met Ser Lys Pro Ile Lys Ile Val Lys Lys Ile Gly Glu Met Thr
645 650 655
Leu Glu Gln Ile Val Glu Asp Ile Tyr His Leu Ser Phe Met Asn Ile
660 665 670
Asp Thr Asp Arg Lys Val Arg Leu Pro Val Thr Thr Asn Tyr Ala Asp
675 680 685
Lys Ser Ser Thr Phe Phe Ser Arg Gly Tyr Leu Ser Ser Gln Lys Lys
690 695 700
Gly Ile Gly Phe Val
705
<210> 70
<211> 755
<212> PRT
<213> artificial sequence
<400> 70
Met Asp Phe Cys Leu Glu Ile Phe Lys Ser Asn Ile Pro Leu Lys Glu
1 5 10 15
Gln Glu Phe Tyr Glu Tyr Thr Leu Ser Ala Val Gly Ser Val Asp Asn
20 25 30
Phe Tyr Gln Leu Ser Gly Lys Ala Glu Tyr Ala Leu Ser Ser Gln Asn
35 40 45
Lys Phe Lys Phe Val Ser Arg Lys Gly Asp Thr Tyr Leu Tyr Ser Leu
50 55 60
Glu Gln Leu Gln Asn Ile Pro Gln Ile Glu Gly Val Lys Ile Glu Phe
65 70 75 80
Thr Gly Cys Lys Lys Leu Asp Val Asn Asn Tyr Lys Glu Val Tyr Ser
85 90 95
Asn Leu Ile Ala Tyr His Ile Asn Lys Ile Leu Lys Gln Lys Lys Thr
100 105 110
Phe Asp Glu Lys Ser Lys Lys Lys Ile Glu Lys Tyr Lys Ile Lys Leu
115 120 125
Lys Lys Ser Ile Tyr Asn Pro Val Met Leu Gln Asn Glu Gly Glu Lys
130 135 140
Tyr Thr Ser Ile Ile Asn Asp Asp Gly Ile Arg Val Tyr Arg Val Phe
145 150 155 160
Asp Ile Met Pro Tyr Ile Asp Glu Asn Arg Tyr Ala Tyr Leu Arg Cys
165 170 175
Asp Ile Arg His Val Phe Glu Ser Glu Lys Thr Ile Tyr Asp Met Met
180 185 190
Lys Glu Asn Lys Lys Ile Ile Gly Leu Lys Val Asp Tyr Ile Trp Thr
195 200 205
Asn Asn Thr Asn Ser Thr Gly Ile Ile Glu Glu Ile Ile Asp Lys Thr
210 215 220
Ile Ser Asp Lys Leu Ser Glu Leu Lys Gly Gln Ser Leu Ile Asp Tyr
225 230 235 240
Phe Ile Asn Thr Asn Gln Ser Tyr Arg Val Asn Lys Phe Thr Glu Glu
245 250 255
Asp Lys Lys Ala Asn Val Ile Lys Val Lys Gly Cys Asn Lys Lys Pro
260 265 270
Leu Tyr Phe Ile Pro His Ser Leu Lys Gln Val Ile Asp Arg Glu Ser
275 280 285
Leu Lys Lys Ile Asp Ser Lys Phe Ser Arg Asp Ile Glu Lys Tyr Ile
290 295 300
Lys Met Asn Met Asn Tyr Arg Met Lys Val Leu Ala Asp Phe Leu Asp
305 310 315 320
Asp Ile Gly Cys Ile Lys Glu Leu Gly Asn Leu Lys Phe Asp Phe Asn
325 330 335
Leu Cys Arg Thr Ser Glu Leu Gly Phe Lys Glu Gly Lys Ile Glu Lys
340 345 350
Pro Tyr Val Leu Val Ala Asn Lys Glu Lys Ile Lys Asn Lys Arg Asp
355 360 365
Val Phe Asn Lys Gly Tyr Phe Lys Lys Pro Asn Asn Lys Ile Arg Val
370 375 380
Ala Val Met Cys Pro Lys Gly Tyr Leu Glu Glu Thr Lys Met Ala Phe
385 390 395 400
Glu Lys Ile Ser Ser Phe Asn Thr Lys Gly Tyr Ile Lys Asn Lys Gly
405 410 415
Lys Leu Tyr Lys Lys Ile Glu Ile Glu Gly Leu Leu Asp Leu Glu Glu
420 425 430
Thr Asn Ile Phe Tyr Glu Tyr Asn Ile Gly Asp Ile Thr Glu Tyr Lys
435 440 445
Arg Thr Ala Leu Asn Leu Ile Lys Asn Asn Glu Lys Val Asp Leu Val
450 455 460
Leu Cys Val Ile Pro Asn Glu His Asp Glu Asn Asn Pro Tyr Ser Glu
465 470 475 480
Phe Lys Thr Val Trp Ala Lys Tyr Lys Ile Pro Ser Gln Met Ile Cys
485 490 495
Val Asp Ser Ile Lys Val Ile Asn Asp Cys Ser Asn Met Asn Asn Tyr
500 505 510
Asn Gly Leu Tyr Tyr Ile Asn Glu Ile Ser Leu Gly Met Leu Val Lys
515 520 525
Ser Gly Gly Val Pro Trp Ile Leu Glu Glu Ile Thr Gly Asp Val Asp
530 535 540
Cys Phe Ile Gly Leu Asp Val Gly Asn Pro Gln Lys Gly Ile Arg Tyr
545 550 555 560
Pro Ser Ser Ser Val Leu Phe Asp Lys Asn Gly Thr Phe Ile Asn Tyr
565 570 575
Phe Lys Pro Glu Ile Pro Gln Thr Gly Glu Ile Ile Val Asp Lys Ile
580 585 590
Leu Gln Glu Ile Phe Asp Asn Ile Ile Leu Ser Phe Glu Thr Lys Phe
595 600 605
Asn Gln Pro Pro Lys His Ile Val Ile His Arg Asp Gly Phe Ala Arg
610 615 620
Glu Asp Ile Asn Trp Tyr Lys Gln Tyr Phe Gln Ser Lys Asn Ile Lys
625 630 635 640
Phe Asp Ile Val Glu Val Lys Lys Gln Gly Ala Val Lys Phe Ala Thr
645 650 655
Lys Lys Gly Asn Val Phe Ile Asn Pro Glu Ala Gly Cys Tyr Val Thr
660 665 670
Asn Gly Gln Tyr Ala Tyr Leu Val Thr Asn Asp Ile Lys Leu Gly Ser
675 680 685
Pro Arg Pro Leu Lys Ile Glu Lys Val Tyr Gly Asp Ile Pro Leu Asp
690 695 700
Asp Ile Val Lys Gln Ile Tyr Tyr Leu Ser Glu Leu His Val Gly Ser
705 710 715 720
Phe Lys Lys Thr Arg Leu Pro Val Thr Thr Glu Tyr Ala Asp Arg Ile
725 730 735
Ser Lys Asn Ile Met Tyr Ile Pro Ser Gly Cys Leu Ser Asp Lys Leu
740 745 750
Phe Phe Leu
755
<210> 71
<211> 630
<212> PRT
<213> artificial sequence
<400> 71
Met Glu Lys Ala His Phe Ile Ser Glu Trp Thr Leu Glu Thr Lys Ala
1 5 10 15
Ser Asp Leu Pro Ile Tyr Leu Tyr Thr Ile Pro Gln Thr Ser Gln Glu
20 25 30
Ile Ser Gln Ile Glu Lys Tyr Thr Ala Lys Ile Lys Tyr Glu Val Met
35 40 45
Arg Gln Asn Pro Gly Ile Leu Leu Glu Ser Ala Gly His Leu Leu Gly
50 55 60
Ser Phe Gln Lys Val Lys Ala Trp Gly Asn Phe Thr Pro Ile Arg Glu
65 70 75 80
Glu Phe Arg Cys Ile Gln Val Glu Ser Ser Val Glu Arg Arg Leu Leu
85 90 95
Glu Arg Leu Leu Ala Arg Ser Phe Glu Asn Ala Gln Asp Pro Asn Ile
100 105 110
Phe Tyr Thr Lys Lys Asn Thr Ile Thr Ile Lys Lys Ala Lys Arg Leu
115 120 125
Asn Asn Asp Ile Glu Met Arg Arg Tyr Leu Gln Phe Glu Met Asn Val
130 135 140
Tyr Pro Ser Gly Leu Ile Ser Ile Gly Phe Asp Leu His His Gln Phe
145 150 155 160
Ser Tyr Arg Lys Ser Leu Tyr Asp Met Ile Leu Lys Gly Val Lys Leu
165 170 175
Glu Glu Asn Cys Gln Val Val Asp Ile Ile Asn Arg Lys Thr Tyr His
180 185 190
Phe His Ser Ile Ser Asp Gln Thr Val Ser Asp Pro Leu Leu Ser Thr
195 200 205
Gly Glu Ser Pro Ile Asp Tyr Tyr Arg Asn Asn Gly Asn Glu Lys Tyr
210 215 220
Val Lys Asn Ile Pro Pro Tyr Thr Pro Ala Ile Ile Cys Phe Ser Pro
225 230 235 240
Thr Ser Ser Lys Pro Leu Tyr Phe Ile Pro Gln Leu Leu Arg Leu Val
245 250 255
Cys Thr Trp Asp Gln Val Pro Ile Asp Gly Lys Lys Glu Thr Lys Ile
260 265 270
Pro Val Asp Asp Arg Val Gln Arg Leu Ile Lys Gly Met Gly Lys Val
275 280 285
Met Asn Asp Trp Lys Asn Asn Cys Pro Asp Leu Pro Ile Arg Phe His
290 295 300
Glu Arg Ser Leu Phe Ala Asp Gln Ala Gly Phe Arg Ile Lys Val Met
305 310 315 320
Lys Lys Pro Thr Leu Leu Phe Gly Gln Gly Val Glu Asp Thr Trp Gly
325 330 335
Gln Arg Gly Leu Lys Lys Gly Gly Val Ile Ser Pro Pro Lys Lys Pro
340 345 350
Ile Glu Cys Gln Ile Leu Ile Asp Asp Asn Val Val Lys Asn Phe Thr
355 360 365
Lys Arg Tyr Lys His Gly Leu Asp Phe Pro Phe Thr Ile Ala Leu Gln
370 375 380
Lys Leu Ser Asn Lys Leu Gly Val Thr Leu Glu Arg Ser Ala Leu Asp
385 390 395 400
Ser Gly Lys Ile Arg Arg Ile His Phe Asp Asp Ala Leu Ser Leu Arg
405 410 415
Glu Glu Leu Gln Glu Ala Ala Lys Ile Met Asn Arg Glu His Pro Leu
420 425 430
Ile Ile Val Ala Lys Lys Glu His Leu Glu Lys Lys Val Gly Ser Arg
435 440 445
Asp Phe Tyr Ser Leu Ile Lys His Leu Leu Gly Arg Asp His Cys Leu
450 455 460
Arg Thr Gln Val Val Thr Tyr Glu Thr Ser Glu Leu Lys Ser Lys Gly
465 470 475 480
Ser Glu Asn Ile Leu Leu Asn Ile Leu Leu Gly Leu Tyr Val Lys Asn
485 490 495
Gly Val His Pro Trp Lys Leu Lys His Pro Leu His Ser Asp Cys Phe
500 505 510
Val Gly Leu Asp Val Ser His Glu Gly Gly Ile His Thr Thr Gly Ile
515 520 525
Ile Gln Val Val Gly Lys Asp Gly Thr Pro Leu Trp Thr Lys Pro Leu
530 535 540
Ser Asn Ser Glu Arg Gly Glu Val Ile Arg Arg Glu Thr Ile Glu Gln
545 550 555 560
Ser Ile Asn His Thr Leu Asp Arg Tyr Lys Gln Lys Glu Gly Arg Tyr
565 570 575
Pro Ser His Ile Thr Phe His Arg Asp Gly Lys Gly His Leu Thr Glu
580 585 590
Val Asn Thr Ile Arg Asp Ile Leu Asn Gln Tyr His Ile Ser Phe Asp
595 600 605
Tyr Val Ala Ile Glu Lys Asn Ile Leu Arg Arg Met Ala Tyr Lys Asp
610 615 620
Asn Pro Ser Pro Asn Gly
625 630
<210> 72
<211> 739
<212> PRT
<213> artificial sequence
<400> 72
Met Glu Ala Tyr Ile Thr Glu Val Thr Ala Thr Gln Trp Ala Asn Glu
1 5 10 15
Ile Ser Leu His Val Tyr Glu Phe Pro Val Glu Asp Pro Thr Lys Lys
20 25 30
Tyr Glu Gly Ala Ser Met Ile Cys Lys Ala Trp Arg Arg Ala Asn Asp
35 40 45
Tyr Met Ala Val Ala Phe Asn Gln Ser Thr Ile Val Thr Phe Glu Pro
50 55 60
Val Asn Ser Tyr Ala Gly Phe Glu Pro Leu Ser Tyr Glu Ile Lys Thr
65 70 75 80
Ile Asn Pro Asn Asn Pro Phe Glu Thr Arg Leu Leu Glu Arg Leu Ile
85 90 95
Lys Glu Ser Leu Leu Ala Val Gly Gln Lys Gln Leu Lys Met Lys Arg
100 105 110
Ala Gly Ser Asp Leu Gln Glu Trp Asn Pro Lys Lys Val Gly Asn Ile
115 120 125
Leu Ile Tyr Pro Ala Leu Ser Phe His Ile Asn Ile Leu Ala Asn Ser
130 135 140
Ile His Ile Gly Phe His Leu Thr His Lys Phe Glu Tyr Glu His Thr
145 150 155 160
Leu Gln Gln Met Ile Glu Arg Gly Glu Val Ile Glu Pro Gly Leu Lys
165 170 175
Val Leu His Ser Asp Ile Arg Asn Asn Tyr Thr Tyr Glu Val Glu Gln
180 185 190
Ile Ala Pro Tyr Ser Val Met Glu Tyr Cys Pro Lys Leu Lys Lys Ser
195 200 205
Ile Tyr Gln Tyr Tyr Asn Ala Lys Gly Asp Thr Arg Val Ile Glu Ala
210 215 220
Leu His Asp Gly Val Lys Val Ile Tyr Ala Lys Pro Ile Tyr Gly Asp
225 230 235 240
Ser Leu Ser Tyr Ala Ala Thr Val Leu Lys Pro Leu Cys Ser Phe Glu
245 250 255
Thr Met Lys Ser Phe Glu Thr Lys Lys Val Met Asp Ile Leu Lys Met
260 265 270
Lys Pro Asp Glu Arg Met Lys Lys Gln Leu Arg Gln Ala Met Asn Leu
275 280 285
Leu Asn Val Tyr Pro Tyr Leu Thr Phe Glu Lys Asn Pro Phe Leu Ile
290 295 300
Glu Ala Asn Asn Tyr Glu Leu Tyr Gln Ile Gln Asp Pro Lys Ile Phe
305 310 315 320
Met Asp Arg Ser Tyr Phe Lys Pro Leu His Gly Met Lys Asn Gly Lys
325 330 335
Leu Phe Lys Ser Gly Thr Ile Arg Leu Ser Ile Phe Met Asp Glu Ala
340 345 350
Ile Glu Lys Lys Leu Gly Ile Ser Lys Ala Leu Val Phe Arg Phe Ile
355 360 365
Lys Ile Leu Gln Gln Phe Ala Lys Gln Gln Gly Val Thr Leu Glu Ile
370 375 380
Ser His Lys Thr Arg Glu Val Lys Glu Lys Phe Thr Glu Glu Phe Phe
385 390 395 400
Gln Gln Phe Ser Trp Glu Ile Arg Glu Leu Glu Ser Ile Phe Ile Asp
405 410 415
Ser Thr Val Leu Ala Ile Ile Thr Asp Glu His Leu Thr Lys Leu Pro
420 425 430
Ile Lys Val Tyr Asp Ala Phe Lys Arg Gln Phe Gly Gly Lys Trp Asp
435 440 445
Ile Ser Thr Gln Val Ile Thr Glu Asn Ser Leu Lys Leu Phe Gln Gln
450 455 460
Leu Leu Lys Arg Asn Gln Leu Asp Leu Phe Asn Pro Asn Asp Glu Val
465 470 475 480
Val Cys Gln Glu Val Ala Asn Arg Ile Lys Ser Asp Asn Leu Phe Tyr
485 490 495
Thr Ile Asn Asn Ile Leu Leu Gly Val Tyr Val Lys Ser Gly Met Gln
500 505 510
Pro Trp Val Leu Asp Glu Arg Thr His Ser Asp Cys Phe Ile Gly Leu
515 520 525
Asp Val Ser His Glu Asp Gly Lys Ser Thr Ala Gly Ile Met Asn Val
530 535 540
Ile Gly Ser Asn Gly His Leu Leu Lys Gln Ser Ala Ile His Gly Ala
545 550 555 560
Leu Ala Gly Glu Lys Ile Asp Thr Lys Thr Leu Glu Glu Ile Leu Met
565 570 575
Asp Val Leu Phe Thr Tyr Lys Asn Gln Phe Gly Asp Phe Pro Lys His
580 585 590
Val Thr Ile His Arg Asp Gly Lys Trp Asn Glu Asp Thr Glu Phe Val
595 600 605
Asp Lys Leu Phe Lys Ala Arg Gly Val Ala Tyr Asp Ile Ile Glu Val
610 615 620
Ile Lys Lys Ser Asn Arg Arg Met Ala Phe Tyr Asn Glu Thr Thr Lys
625 630 635 640
Lys Phe Glu Thr Arg Gln Gly Val Tyr Tyr Lys Arg Glu Lys Glu Ala
645 650 655
Phe Leu Cys Ala Thr Asp Pro Arg Glu Asn Ile Gly Met Ala Gln Pro
660 665 670
Ile Lys Ile Val Gln Tyr Thr Lys Thr Leu Thr Phe Glu Gln Leu Ile
675 680 685
Glu Asp Val Tyr Arg Leu Ser Phe Met His Ile His Ser Leu Asn Lys
690 695 700
Met Arg Leu Pro Ala Thr Ile His Tyr Ala Asp Leu Ser Ser Thr Ala
705 710 715 720
Tyr Gln Arg Gly Gln Val Ala Pro Arg Thr Thr Asn Val Thr His Leu
725 730 735
Pro Phe Val
<210> 73
<211> 709
<212> PRT
<213> artificial sequence
<400> 73
Met Asn Gln Tyr Tyr Leu Ser Glu Trp Leu Ser Gly Thr Asn Ala Ala
1 5 10 15
Glu Leu Pro Val His Ile Tyr Thr Ile Pro Leu Ser Met Glu Glu Asn
20 25 30
Arg His Ser Met Gly Gly Lys Val Cys Tyr Gly Leu Ser Lys Gln Asn
35 40 45
Gln Phe Gln Thr Met Val Phe Phe Asp Gln Tyr Ile Ala Ser Phe Lys
50 55 60
Ala Ile Thr Asn Trp Gln Gly Tyr His Cys Leu His Tyr Glu Asn Arg
65 70 75 80
Pro Ile Lys Leu Ala Ala Ser Tyr Glu Arg Thr Leu Leu Glu Arg Leu
85 90 95
Ile Lys Lys Glu Leu Glu Gln Arg Ser Arg Leu Thr His Val Ile Asp
100 105 110
Arg Gly Ala Phe Arg Leu Lys Gln Ser Lys Pro Met Asn Ala Ala Glu
115 120 125
Leu Leu Ile Tyr Pro Ala Ile Gln Met Asn Ile Glu Val Gln Val Asn
130 135 140
Gly Asp Ile Ile Ala Gly Phe Asp Tyr Val His Arg Leu Glu Tyr Lys
145 150 155 160
Glu Asn Val Gln Ala Tyr Met Thr Asp Gln Lys Ile Asn Met Thr Gly
165 170 175
Arg Ser Val Val Asp Thr Thr His Ala Arg Thr Tyr Glu Tyr Glu Phe
180 185 190
Val Glu Val Ala Pro Tyr Lys Ala Gly Glu Val Ser Pro Tyr Leu Lys
195 200 205
Glu Ser Val Ile Asp Tyr Tyr Ile Arg Lys Lys Glu Glu Arg Lys Leu
210 215 220
Asn Gly Val Ser Asn Gln Ser Pro Val Ile His Val Lys Asn Arg Glu
225 230 235 240
Gly Ala Ile Phe Pro Tyr Leu Pro His Leu Leu Lys Leu Ser Cys Ser
245 250 255
Phe Asp Ser Leu Pro Ser His Leu Ser Lys Ala Ala Ser Lys Thr Ile
260 265 270
Lys Met Lys Pro His Glu Lys Met Thr Glu Leu Tyr Lys Glu Ala Tyr
275 280 285
Arg Leu Leu Arg Lys Leu Pro Met Ile Thr Phe Pro Gln Asp Asn Ile
290 295 300
Arg Ala Val Lys Leu Gly Tyr Glu Val Gly Tyr Ala Ser Pro Pro Leu
305 310 315 320
Leu Gln Phe Gly Asn Lys Val Thr Asn Lys Lys Val Thr Glu Gly Leu
325 330 335
Ser Lys Gly Gly Val Tyr Lys Gly Gly Asn Val His Val Ser Phe Phe
340 345 350
Val Asp Pro Leu Leu Gln Gln Asn Pro Thr Ala Arg Lys Asn Ile Gly
355 360 365
Gln Phe Ile Gln Leu Leu Ile Gln Gln Ser Ala Lys Leu Gly Val Asn
370 375 380
Leu Ile Val Ser Asp Lys Pro Arg Ala Leu Arg Gly Gln Leu Ser Pro
385 390 395 400
Gln Leu Leu Thr Ser Glu Glu Phe Pro Tyr Gln Leu Lys Ser Ile Ser
405 410 415
Arg Tyr Phe Asp Gly Thr Val Ile Val Ile Ala Ser Gln Gln Thr Ile
420 425 430
Asp Gln Val Tyr Arg Leu Ile Lys Lys Glu Phe Gly Gly Lys Gln Asp
435 440 445
Met Ile Thr Gln Phe Val Thr Tyr Thr Glu Gln Leu Ile Asp Ile Thr
450 455 460
Lys Ser Phe Tyr Leu Ile Gln Asn Leu Leu Leu Gly Ile Phe Val Lys
465 470 475 480
Ser Gly Lys Gln Pro Trp Val Leu Gly Asp Ser Leu His Ser Asp Cys
485 490 495
Phe Ile Gly Leu Asp Val Ser His Glu Ser Gly Asn His Ala Cys Gly
500 505 510
Met Ile Gln Thr Ile Ser Arg Asp Gly Thr Leu Ile Gln Gln Lys Ser
515 520 525
Leu Ser Met Pro Glu Thr Gly Glu Lys Ile His Ser Ala Thr Ile Glu
530 535 540
Glu Leu Leu Tyr Asp Thr Ile His Phe Tyr Gln Glu His Tyr Lys Glu
545 550 555 560
Pro Pro Arg His Ile Thr Phe His Arg Asp Gly Phe Cys Arg Glu Asp
565 570 575
Leu Ala Phe Ile Glu Arg Gln Leu Ala Lys Ala Asn Ile Ala Phe Asp
580 585 590
Tyr Val Glu Ile Leu Lys Asn Val Asn Arg Arg Met Ala Val Tyr His
595 600 605
Gln Glu Arg Trp Thr Thr Glu Gln Ser Leu Tyr Tyr Arg Lys Asn Asn
610 615 620
Val Ala Tyr Leu Cys Ser Thr Ser Pro Lys Glu Tyr Val Gly Met Ala
625 630 635 640
Lys Val Met Lys Ile Val Gln Lys Thr Asn His Leu Pro Phe Asp His
645 650 655
Ile Ile Ser Asp Val Tyr Lys Leu Ser Phe Met His Ile His Ser Met
660 665 670
Leu Lys Thr Arg Leu Pro Ile Thr Ile His Tyr Ala Asp Leu Ser Ser
675 680 685
Thr Phe His Asn Arg Asp Met Leu His Pro Ala Thr Gln His Thr Lys
690 695 700
Ser Leu Pro Phe Val
705
<210> 74
<211> 699
<212> PRT
<213> artificial sequence
<400> 74
Met Asn Asp Phe Gln Val Leu Thr Glu Trp Thr Leu Asp Thr Arg Ala
1 5 10 15
Thr Glu Phe Ile Ile His Ile Tyr Thr Met Pro Ile Asn Asp Leu Asn
20 25 30
Lys Ser His Thr Glu Ser Tyr Glu Leu Val Lys Thr Leu Arg Arg Leu
35 40 45
Asn Asn Thr Lys Glu Ile Val Phe Tyr Glu Gln Gln Ile Ala Ala Leu
50 55 60
Thr Lys Val Glu Asn Trp Gly His Tyr Thr Arg Gly Asp Tyr Gln His
65 70 75 80
Arg Cys Ile Lys Leu Ser Val Pro Arg Glu Arg Glu Leu Leu Gln Arg
85 90 95
Leu Leu Leu Lys Val Val Gly Ala Arg Gln Pro Lys Lys Val Tyr Ala
100 105 110
Glu Gly Gly Leu Phe Ile Asn Ala Ser Pro Gln Tyr Lys Ile Glu Asn
115 120 125
Ile Asn Ile His Glu Ala Leu Asn Leu Asp Phe Ser Val Thr Gln Glu
130 135 140
Gly Leu Ile Ile Val Gly Phe Asp Phe Thr His Lys Leu Tyr Tyr Lys
145 150 155 160
Asp Thr Leu Leu Glu Phe Val Lys Arg Asn Gln Ile Gln Lys Gly Asp
165 170 175
Arg Val Ile Asp Pro Ile Tyr His Ile Ser Tyr Val Tyr Asp Glu Val
180 185 190
Ala Pro Tyr Thr Val Ser Glu Ser Ser Pro Tyr Leu Gly Gln Ser Ile
195 200 205
Leu Gln Tyr Tyr Lys Asn Lys Asp Trp Ile Leu Lys Lys Leu Asn Thr
210 215 220
Asp Met Ser Val Val His Val Arg Asn Lys Glu Asn Lys Ile Phe Pro
225 230 235 240
Tyr Ala Pro Val Phe Leu Lys Lys Glu Cys Ser Leu Ser Ser Leu Asp
245 250 255
Gln Arg Ile Val Thr Lys Ile Asn Arg Val Ile Lys Leu Gly Pro Asn
260 265 270
Glu Lys Met Thr Lys Ser Ile Arg Glu Val Gln Asn Ile Leu Ser Arg
275 280 285
Phe Glu Val Leu Arg Leu Asn Lys Asn Asn Leu Leu Val Ser Asn Gln
290 295 300
Gly Tyr Lys Ile Lys Tyr Phe Pro Val Pro Ser Leu Arg Phe Gly Lys
305 310 315 320
Asn Val Thr Ser Lys Ser Leu Lys Asn Gly Leu Ile Lys Gly Gly Val
325 330 335
Val Asp Pro Arg Asn Leu Glu Leu Ala Tyr Phe Ile Asp Pro Val Ile
340 345 350
Ile Lys Asn Asn Thr Glu Ser Ile Glu Val Phe Met Lys Asn Leu Glu
355 360 365
Glu Lys Ser Lys Gln Leu Gly Val Pro Leu Gln Arg Leu Lys Lys Gly
370 375 380
Arg Ser Phe Tyr Asn Gln Leu Asp Thr Gln Met Phe Ser Ser Pro Asn
385 390 395 400
Glu Leu Val Leu Gly Leu Lys Lys Ile Ala Lys Glu Phe Asn Cys Leu
405 410 415
Thr Val Val Ile Thr Thr Gln Gln Asn Ile Asp Lys Cys Tyr Gly Ala
420 425 430
Ile Lys Lys Glu Phe Gly Gly Asn Tyr Asp Ile Pro Thr Gln Phe Val
435 440 445
Thr Ala Asp Thr Ala Lys Glu Lys Asn Asp Tyr Ile Leu Leu Asn Ile
450 455 460
Leu Leu Gly Ile Tyr Ala Lys Ala Ser Ile Gln Ser Trp Ile Leu Lys
465 470 475 480
Glu Pro Leu His Ser Asp Cys Phe Ile Gly Leu Asp Val Ser His Glu
485 490 495
Glu Asn Arg His Ser Thr Gly Leu Val Gln Val Val Gly Lys Asp Gly
500 505 510
Arg Val Leu Ser Ser Lys Ala Met Ser Thr Ile Glu Ser Gly Glu Arg
515 520 525
Ile Arg Asp Glu Thr Met Lys Glu Ile Val Tyr Glu Ala Ile His Ser
530 535 540
Tyr Glu Asn Gln Tyr Gly Tyr Arg Pro Lys His Val Thr Phe His Arg
545 550 555 560
Asp Gly Phe Cys Arg Glu Asn Ile Asp Asn Ile Glu Tyr Ile Leu Lys
565 570 575
Asn Leu Gly Val Leu Phe Asp Tyr Val Glu Val Ile Lys Lys Ser Asn
580 585 590
Arg Arg Met Ala Asn Phe Leu Ser Lys Glu Glu Gly Trp Lys Thr Glu
595 600 605
Ile Gly Ala Ser Tyr Leu Lys Asp Asp Leu Ala Tyr Leu Cys Ser Thr
610 615 620
Ala Pro Gly Lys Gln Val Gly Met Ala Ile Pro Val Lys Ile Thr Gln
625 630 635 640
Val Thr Gly His Leu Thr Met Ser Ala Ile Val Ser Asp Ile Phe Asn
645 650 655
Leu Ser His Met His Val Gly Ser Leu Ile Lys Ser Arg Leu Pro Ile
660 665 670
Ser Thr Tyr Tyr Ala Asp Leu Ser Ser Thr Phe Phe Asn Arg Gly Trp
675 680 685
Ile Ser Ser Arg Ser Asn Gly Leu Gln Phe Val
690 695
<210> 75
<211> 709
<212> PRT
<213> artificial sequence
<400> 75
Met Phe His Met Asn Thr Pro Thr Thr His His Ile Leu Thr Glu Trp
1 5 10 15
Glu Ser Asp Thr Asn Ala Ser Asn Leu Val Val His Leu Tyr Ser Leu
20 25 30
Pro Val Arg Asn Val Phe Glu Leu His Asn Glu Asn Gly His Ala Cys
35 40 45
Ser Glu Leu Arg Arg Leu Asn Lys Thr Asn Val Ile Asp Phe Phe Glu
50 55 60
Gln Phe Ile Ala Ser Trp Gln Pro Ile Glu Asn Trp Gly Lys Tyr Thr
65 70 75 80
Phe Thr Asn His Glu Cys Arg Ser Ile Asn Ala Leu Val Ser Thr Glu
85 90 95
Arg Thr Val Leu Glu Arg Leu Leu Leu Arg Thr Ile Glu Ser Ala Gln
100 105 110
Pro Arg Asn Glu Ile Ala Ala Gly Ser Arg Lys Phe Thr Trp Leu Lys
115 120 125
Ala Glu Lys Val Val Gln Asn Ile Ser Ile His Arg Val Ile His Cys
130 135 140
Asp Val Ser Ile Asn Ile Asn Gly Val Ile Thr Val Gly Phe Asp Leu
145 150 155 160
Asn His Ser Phe Arg Thr Asn Asp Ser Val Phe Asp Leu Met Lys Ser
165 170 175
Lys Ala Ile Ile Lys Gly Asp Arg Val Ile Asp Lys Tyr Asn Asn Leu
180 185 190
His Tyr Glu Phe Asp Lys Val Thr Glu Tyr Thr Ile Ser Asp Val Val
195 200 205
Pro Glu Leu Gly Gln Ser Val Ile Asn Tyr Phe Val Arg Glu Arg Lys
210 215 220
Gln Thr Trp Lys Val Asp Lys Leu Asp Pro Ser Met Pro Val Val Tyr
225 230 235 240
Val Lys Met Lys Asn Arg Gln Ala Pro Ile Ala Tyr Ala Pro Ala Met
245 250 255
Leu Gln Lys Glu Leu Thr Phe Glu Ser Leu Pro Val Ala Val Val Arg
260 265 270
Gln Thr Ser Glu Val Tyr Lys Gln Asn Ala Asn Gln Lys Ile Lys Ile
275 280 285
Leu Leu Asp Glu Met Gln Asn Ile Leu Lys Arg Thr Asp Lys Leu Gln
290 295 300
Phe Ser Lys Gln Lys Leu Leu Val Gln Gln Ser Gly Tyr Lys Val Lys
305 310 315 320
Gln Ile Glu Ile Pro Asn Leu Thr Phe Gly Lys Asn Val Thr Gln Ser
325 330 335
Gln Pro Arg Tyr Gly Leu Glu Lys Gly Gly Val Val Leu Ser Lys Pro
340 345 350
Leu Ser Ile Asn Leu Leu Val Tyr Pro Glu Leu Ile Asn Thr Lys Leu
355 360 365
Asn Ala Ile Thr Ala Phe Asn Asp Lys Leu Ile Ala Leu Ser His Lys
370 375 380
Trp Gly Val Pro Leu Thr Ile Leu Lys Lys Ser Glu Thr Tyr Arg Asn
385 390 395 400
Lys Ser Ile Asp Phe Thr Asn Pro His Gln Phe Ala Ile Leu Leu Lys
405 410 415
Glu Leu Ala Asn Tyr Ser Phe Gln Glu Leu Thr Leu Val Ile Ile Pro
420 425 430
Glu Lys Val Ala Gly Met Trp Tyr Asp Leu Ile Lys Lys Glu Phe Gly
435 440 445
Gly Asn Ser Ser Val Pro Thr Gln Phe Ile Thr Ile Glu Thr Leu Gln
450 455 460
Lys Ala Asn Asp Phe Ile Leu Gly Asn Leu Leu Leu Gly Leu Tyr Ser
465 470 475 480
Lys Ser Gly Ile Gln Pro Trp Ile Leu Asn Ser Ser Leu Ser Ser Asp
485 490 495
Cys Phe Ile Gly Leu Asp Val Ser His Glu Ser Gly Arg His Ser Ala
500 505 510
Gly Ile Val Gln Ile Val Gly Lys Asp Gly Arg Val Leu Ser Ser Arg
515 520 525
Ala Asn Thr Ser Asn Glu Ala Gly Glu Lys Ile Arg His Glu Thr Met
530 535 540
Cys Gln Ile Ile Tyr Ser Ala Ile Asp Gln Tyr Gln Arg His Tyr Asn
545 550 555 560
Glu Lys Pro Arg His Val Thr Phe His Arg Asp Gly Leu Cys Arg Glu
565 570 575
Asp Leu Asn Ser Leu Asp Glu Val Phe Asp Ser Leu Gly Val Asp Tyr
580 585 590
Asp Met Val Glu Ile Ile Lys Lys Thr Asn Arg Arg Met Ala Ile Asn
595 600 605
Val Asp Lys Gln Gly Trp Glu Thr Lys Ser Gly Leu Cys Tyr Val Lys
610 615 620
Asp Asn Trp Ala Tyr Leu Ile Ser Thr Asn Pro His Pro Arg Val Gly
625 630 635 640
Thr Ala Gln Pro Ile Lys Ile Val Lys Lys Gln Gly Ser Leu Ser Leu
645 650 655
Glu Ala Ile Val Gln Asp Ile Tyr His Leu Ser Phe Met His Ile Gly
660 665 670
Ser Leu Leu Lys Cys Arg Leu Pro Ile Thr Thr Tyr Tyr Ala Asp Leu
675 680 685
Ser Ser Thr Phe Phe Asn Arg Gln Trp Ile Pro Ile Asp Ser Gly Glu
690 695 700
Ser Leu His Phe Val
705
<210> 76
<211> 739
<212> PRT
<213> artificial sequence
<400> 76
Met Glu Pro Tyr Ile Thr Glu Ala Thr Ala Ile Gly Leu Ala Ser Asp
1 5 10 15
Ile His Leu His Val Tyr Glu Phe Pro Val Asp Asn Pro Leu Lys Lys
20 25 30
Tyr Glu Gly Val Ser Asp Ile Cys Arg Glu Trp Lys Arg Ala Asn Gly
35 40 45
Tyr Met Ala Val Ala Tyr Asn Gln Ser Thr Ile Ala Thr Leu Glu Pro
50 55 60
Val Val Asn Tyr Ala Gly Phe Glu Pro Leu Ser Tyr Gln Glu Lys Pro
65 70 75 80
Ile Asp Pro Asp Asn Pro Phe Glu Arg Ser Leu Leu Glu Arg Leu Leu
85 90 95
Lys Glu Gly Leu Leu Thr Ala Gly Gln Gln Lys Leu Lys Leu Lys Arg
100 105 110
Val Gly Ala Asp Leu Gln Glu Trp Glu Pro Lys Arg Val Gly Arg Ile
115 120 125
Leu Ile Tyr Pro Ala Leu Ser Phe His Val Asn Val Leu Asn Asn Arg
130 135 140
Val His Ile Gly Phe Ala Met Thr His Lys Phe Glu Tyr Glu Val Thr
145 150 155 160
Leu Gln Gln Met Leu Glu Gln Gly Glu Val Val Glu Glu Gly Leu Lys
165 170 175
Val Val His Ser Asp Val Trp Asn Asn Tyr Thr Tyr Glu Val Glu Gln
180 185 190
Ile Ala Pro Tyr Ser Val Met Asp Met Cys Pro Lys Leu Lys Lys Pro
195 200 205
Ile His Gln Tyr Tyr Val Asp Lys Gly Asn Gln Lys Met Ala Asp Thr
210 215 220
Leu His Glu Asn Val Lys Val Ile Tyr Ala Lys Pro Leu His Gly Asp
225 230 235 240
Ser Leu Ser Tyr Ala Ala Ser Val Leu Lys Pro Leu Cys Ser Phe Glu
245 250 255
Thr Met Lys Pro Phe Glu Ala Lys Lys Ile Met Asp Val Leu Lys Leu
260 265 270
Lys Pro Asp Glu Arg Met Arg Lys Gln Leu Glu Gln Ala Lys Lys Leu
275 280 285
Leu Ser Val Phe Ser Tyr Leu Gln Phe Glu Lys Arg Pro Phe Leu Leu
290 295 300
Gln Ala Asn Gln Tyr Glu Leu Met Thr Leu Ser Glu Pro Ala Val Phe
305 310 315 320
Thr Asn Lys Arg Phe Asn Lys Pro Ile Tyr Gly Leu Lys Asn Gly Pro
325 330 335
Leu Phe Lys Gly Gly Thr Val Thr Leu Ser Ile Phe Phe Asp Glu Ala
340 345 350
Ile Glu Ser Ser Leu Gly Leu Ser Lys Lys Leu Val Phe Gln Phe Val
355 360 365
Lys Val Leu Gln Lys Ile Ala Glu Gln Asn Gly Val Ile Met Lys Ile
370 375 380
Ser His Glu Thr Lys His Ile Lys Gly Lys Leu Asn Glu Ser Phe Phe
385 390 395 400
Gln His Phe Ser Trp Glu Ile Arg Glu Leu Glu Asn Val Phe Thr Asp
405 410 415
Thr Thr Val Leu Ala Leu Met Thr Glu Glu His Leu Thr Lys Leu Pro
420 425 430
Asn Lys Leu Tyr Asn Glu Phe Lys Arg Gln Phe Gly Gly Lys Trp Asp
435 440 445
Ile Ser Ser Gln Ile Ile Thr Glu Lys Val Leu Lys Thr Phe Gln Tyr
450 455 460
Ala Leu Thr Arg His Gln Leu Thr Asp Phe Asn Val Asn Asp Glu Lys
465 470 475 480
Glu Cys Glu Arg Val Ala Asp Ile Val Lys Asn Asp Ser Leu Ser Tyr
485 490 495
Pro Val Phe Asn Ile Leu Leu Gly Ile Tyr Val Lys Ser Gly Met Gln
500 505 510
Pro Trp Val Leu Ala Glu Arg Ala His Ser Asp Cys Phe Ile Gly Leu
515 520 525
Asp Val Ser His Glu Asp Gly Lys Ser Ala Ala Gly Ile Met Asn Val
530 535 540
Ile Gly Ser Asn Gly His Leu Ile Lys Gln Ser Ala Leu Asn Gly Val
545 550 555 560
Leu Ala Gly Glu Lys Ile Asp Glu Pro Thr Leu Asn Glu Ile Ile Thr
565 570 575
Glu Val Leu Tyr Ser Tyr Gln Lys Gln Phe Gly His Phe Pro Lys His
580 585 590
Val Thr Ile His Arg Asp Gly Lys Trp Arg Glu Ser Ser Glu Leu Val
595 600 605
Gly Arg Leu Phe Lys Asp Arg Asn Val Ala Tyr Asp Ile Val Glu Val
610 615 620
Ile Lys Lys Pro Asn Arg Arg Met Ala Phe Tyr Asn Asn Glu Thr Gly
625 630 635 640
Lys Phe Glu Thr Lys Gln Gly Val Cys Tyr Val Arg Asn Gln Glu Ala
645 650 655
Phe Leu Cys Ser Thr Asn Pro Arg Glu Thr Ile Gly Met Ala Gln Pro
660 665 670
Val Lys Ile Val Gln Leu Thr Asn Thr Leu Pro Phe Lys Gln Ile Ile
675 680 685
Gln Asp Cys Tyr Asp Leu Ser Phe Met His Ile His Ala Val Asn Lys
690 695 700
Met Arg Leu Pro Ala Thr Ile His Tyr Ala Asp Leu Ser Ser Thr Ala
705 710 715 720
Tyr Gln Arg Gly Gln Val Ala Pro Arg Thr Thr Asn Gly Thr His Leu
725 730 735
Pro Phe Val
<210> 77
<211> 676
<212> PRT
<213> artificial sequence
<400> 77
Met Ala Ile Ala Glu Ile Lys Asp Met Ala Gly Tyr Glu Ala Lys Ser
1 5 10 15
Tyr Asp Tyr Arg Ile Ile Asp Glu His Ser Asn Phe Glu Cys Gly Leu
20 25 30
Leu Glu Gln Leu Ile Lys Ala Ser Leu Leu Lys Ala Gly Thr His Arg
35 40 45
Leu Asp Leu Lys Gln Val Gly Tyr Asp Leu Gln Lys Lys Gln Gly Glu
50 55 60
Lys Ala Gly Glu Val Leu Val Tyr Pro Ala Leu Ser Ile His Val Asn
65 70 75 80
Ile Ile Asp Asn Lys Ile His Ile Gly Phe Asn Leu Thr His Lys Phe
85 90 95
Glu Tyr Thr Ile Thr Leu Gln Gln Met Ile Glu Arg Asn Gly Val Ile
100 105 110
Lys Asp Gln Leu Glu Leu Val Asp Thr Ser Asn Pro Tyr Ser Asn Tyr
115 120 125
Thr Tyr Phe Phe Asp His Leu Ala Asp Tyr Gly Val Tyr Asp Asn Ser
130 135 140
Pro Leu Met Asn Gln Ser Ile Val Glu Tyr Phe Asn Gln Lys Gly Gln
145 150 155 160
Lys Phe Lys Ile Gly Leu Leu Ser Lys Ser Thr Lys Val Ala His Val
165 170 175
Lys Thr Arg Asp Gly Lys Leu Ile Val Met Ala Ala Gln Phe Leu Lys
180 185 190
Pro Val Cys Ser Tyr Lys Ser Met Lys Ala Asn Glu Ile Ser Ala Val
195 200 205
Asn Lys Val Ile Arg Leu Lys Pro Leu Phe Arg Met Lys Gln Thr Met
210 215 220
Glu Asp Ser Leu Asp Ile Leu Asn Ser Val Lys Tyr Leu Thr Phe Ser
225 230 235 240
Pro Glu Pro Phe Leu Ala Lys Asn Asn Gly Tyr Glu Ile Lys Lys Leu
245 250 255
Glu Asp Ser Thr Val Leu Phe Asp Lys Pro Gln Lys Trp Pro Val Tyr
260 265 270
Gly Leu Lys Asn Gly Lys Ile Tyr Lys Gly Gly Glu Met Thr Val Ser
275 280 285
Leu Phe Val Asp Glu Thr Thr Leu Asn Glu Ser Ile Asp Lys Val Phe
290 295 300
Val Tyr Lys Tyr Phe Cys Ile Leu Arg Glu Ile Ala Arg Lys His Gly
305 310 315 320
Val Lys Ile Asp Ile Ser Asn Gln Thr Arg Ser Ile Ser Gly Lys Leu
325 330 335
Asn Gln Glu Phe Phe Lys Asn Phe Asp Trp Gln Ile Lys Glu His Glu
340 345 350
Ala Val Phe Lys Asn Thr Thr Val Leu Ala Val Leu Ser Val Pro His
355 360 365
Leu Glu Leu Tyr Glu Pro Phe Lys Lys Gln Phe Gly Gly Asn Trp Asp
370 375 380
Ile Ser Ser Gln Val Ile Ser Val Glu Arg Leu Lys Glu Phe Gln Lys
385 390 395 400
Met Leu Ser Ser Asn Lys Glu Leu Ser Phe Asn Pro Lys Asp Asp Glu
405 410 415
Ala Val Lys Arg Ile Ala Leu Ser Val Gln Asn Asp Arg Asn Leu Ser
420 425 430
Tyr Thr Phe Tyr Asn Ile Leu Leu Gly Leu Tyr Val Lys Ser Gly Met
435 440 445
Gln Pro Trp Val Leu Asn Lys Lys Thr Asn Ser Asp Cys Phe Ile Gly
450 455 460
Leu Asp Val Ser His Glu Lys Gly Arg Ser Thr Ala Gly Ile Ile Asn
465 470 475 480
Val Ile Gly Asn Asp Gly Arg Leu Ile Lys Gln Ser Ala Val Gly Gly
485 490 495
Ala Asn Ala Gly Glu Lys Val Ser Asp Glu Leu Leu Lys Asp Thr Leu
500 505 510
Asn Glu Val Leu His Lys Tyr Lys Val Gln Phe Asp Glu Leu Pro Lys
515 520 525
His Val Thr Ile His Arg Asp Gly Phe Trp Arg Glu Asn Thr Glu Leu
530 535 540
Ile Ser Glu Val Leu Gly Ala Lys Gly Ile Gln Phe Asp Ile Val Glu
545 550 555 560
Val Ile Lys Ser Pro Lys Arg Arg Met Ala Tyr Tyr Asp Ser Lys Asp
565 570 575
Asn Lys Met Glu Thr Arg Gln Gly Thr Tyr Tyr Phe Arg Gly Lys Glu
580 585 590
Ala Leu Leu Cys Ala Thr Asn Pro Arg Glu Gln Ile Gly Met Ala Leu
595 600 605
Pro Ile Lys Val Val Gln Lys Thr Ser Thr Leu Ser Phe Glu Gln Val
610 615 620
Ile Ser Asp Val Tyr Ala Leu Ser Phe Met His Val His Ala Leu Asn
625 630 635 640
Lys Thr Arg Leu Pro Ala Thr Thr His Tyr Ala Asp Leu Ser Ser Thr
645 650 655
Phe Tyr Gln Arg Gly Met Val Ala Ala Arg Thr Thr Asn Glu Thr His
660 665 670
Leu Pro Phe Val
675
<210> 78
<211> 706
<212> PRT
<213> artificial sequence
<400> 78
Met Ser Tyr His Ala Leu Ser Gln Phe Lys Leu Ile Gln Thr Ala Lys
1 5 10 15
Asp Val Pro Ile Tyr Ile Tyr Val Leu Pro Ile Asn Asn Leu Asn Glu
20 25 30
Arg His Ser Glu Leu Phe Asp Val Ala Gln Val Ile Lys Lys Lys Asn
35 40 45
Lys Thr Asp Leu Val Ala Phe Asn Glu Asn Met Ile Gly Ser Phe Glu
50 55 60
Pro Leu Lys Glu Trp Glu Asp His Ala Pro Val Ser Ser Glu Gln Arg
65 70 75 80
Thr Ile Asp Leu His Asn Pro Arg Glu Val Arg Leu Leu Glu Arg Leu
85 90 95
Val Gln Ala Ser Val Val Lys Glu Gly Ala Lys Lys Ala Lys Ser Tyr
100 105 110
Tyr Tyr Arg Gly Ser Glu Ile Val Ser Tyr Asp Ser Lys Asn Ile Glu
115 120 125
Asp Glu Val His Val His Lys Arg Tyr Lys Met Asp Thr Thr Val Glu
130 135 140
Arg Asp Gly Glu Ile Phe Val Gly Leu Glu Leu Ser His Gln Leu Phe
145 150 155 160
Arg Val Pro Ser Leu Leu Thr Asn Leu Gln Lys Asn Glu Asp Ile Ile
165 170 175
Gly Met Glu Val Thr Asp Lys Arg Lys Gln Lys Tyr Val Val Glu Lys
180 185 190
Val Ser Asp Val Lys Val Gly Asp Val His Pro Val Leu Gly Gln Ser
195 200 205
Ile Lys Asp Tyr Tyr Ser Asn Asn Gly Arg Ala Lys Glu Ile Ser Ile
210 215 220
Ala Lys Asp Asp Ser Pro Val Val Ser Val Ala Lys Glu Glu Gly Gly
225 230 235 240
Lys Pro Ile Phe Tyr Ala Pro Glu Leu Leu Ser Gln Ile Cys Thr Met
245 250 255
Asn Ser Phe Gly Ser Arg Ile Ile Lys Lys Ile Lys Lys Glu Leu Thr
260 265 270
Met Asp Pro Thr Arg Lys Phe Gln Met Met Ile Asp Val Gly Met Asp
275 280 285
Val Ile Asn Arg Ser Arg Phe Gln Thr Ser Lys Lys Asn Val Leu Ile
290 295 300
Glu Asn Gln Gly Tyr Asp Thr Tyr Gln Met Asn Pro Pro Ser Phe Ser
305 310 315 320
Phe Gly Asn Gly His Ser Asn Arg Ser Ile Asn Tyr Gly Leu Lys Lys
325 330 335
Ala Gly Ile Tyr Glu Ser Gly Ala Glu Pro Leu Pro Val His Ile Leu
340 345 350
Leu Asp Asn Asn Val Leu Thr Arg Phe Gln Thr Asn Glu His Asp Lys
355 360 365
Asn Gln Val Thr Phe Phe Val Glu Lys Leu Lys Glu Glu Ala Gly Arg
370 375 380
Met Gly Arg Gly Ile Asp Val Lys Asn Val Gly Leu Asp Tyr Lys Asn
385 390 395 400
Val Cys Phe Asp Ser Pro Ser Glu Leu Arg Asn Thr Leu Lys Thr Ile
405 410 415
Gly Gly Lys Phe Thr Glu Pro Val Ile Val Ile Thr Glu Asp Ser Arg
420 425 430
Ala Glu Thr Cys Tyr Glu Val Ile Lys Arg Glu Leu Gly Lys Arg Lys
435 440 445
Gly Leu Pro Thr Gln Met Ile Gln Met Asp Thr Thr Gly Asn His Tyr
450 455 460
Ser Ile Gln Asn Ile Leu Leu Gly Ile Tyr Ala Lys Ser Gly Val Gln
465 470 475 480
Ser Trp Leu Leu Asn Gln Lys Leu His Ser Asp Leu Phe Ile Gly Leu
485 490 495
Asp Val Ser His Glu Asp Gly Val His Ala Ala Gly Ile Val Gln Ile
500 505 510
Val Gly Lys Asp Gly Arg Val Leu Tyr Ala Asp Ser Val Ser Ser Phe
515 520 525
Glu Ala Gly Glu Lys Ile Lys Ser Glu Thr Leu Val Asp Ile Val Ser
530 535 540
Glu Ala Val His Gln Phe Lys Asn His Phe Pro His Glu Thr Leu Glu
545 550 555 560
His Met Thr Phe His Arg Asp Gly Gly Gly Phe Glu Glu Glu Ile Glu
565 570 575
Ala Ile Ser Gly Glu Leu Glu Gly Leu Asp Ile Ala Phe Asp Tyr Val
580 585 590
Ser Val Val Lys Asn Pro Arg Arg Arg Met Ala Val Tyr Glu Gly Asn
595 600 605
Gln Trp Lys Thr Glu Gln Gly Arg Val Tyr Thr Lys Glu Asp His Ala
610 615 620
Tyr Met Cys Leu Thr Asn Pro Thr Ala Val Val Gly Met Ala Lys Pro
625 630 635 640
Ile Arg Val Thr Gln Lys His Ala Ser Leu Pro Phe Gln Asp Ile Leu
645 650 655
Gln Asp Ile His Asp Leu Ser Tyr Met His Ile Ala Ser Leu Arg Lys
660 665 670
Ala Arg Leu Pro Val Thr Val Asn Tyr Ala Asp Lys Ala Ser Thr Phe
675 680 685
Phe Asn Arg Gly Tyr Leu Pro Asn Thr Pro Met Gly Lys Ser Leu His
690 695 700
Phe Val
705
<210> 79
<211> 740
<212> PRT
<213> artificial sequence
<400> 79
Met Glu Ala Tyr Ile Thr Glu Ala Thr Ala Ala Gln Leu Ala Asn Glu
1 5 10 15
Ile Ser Leu His Ile Tyr Glu Phe Pro Val Glu Asp Pro Thr Lys Lys
20 25 30
Tyr Glu Gly Val Tyr Lys Ile Cys Ser Ala Trp Lys Arg Ala Asn Gly
35 40 45
Tyr Met Pro Ile Ala Tyr Asn Gln Ser Thr Ile Ala Thr Leu Glu Pro
50 55 60
Val Asn Asp Tyr Ala Gly Phe Glu Pro Leu Ser Tyr Arg Val Asp Thr
65 70 75 80
Ile Asp Cys Glu Asn Ser Phe Glu Arg Ser Leu Leu Glu Arg Ile Ile
85 90 95
Lys Glu Ser Leu Leu Ser Ile Gly Gln Lys Arg Leu Lys Leu Lys Arg
100 105 110
Val Gly Asn Asp Leu Gln Glu Trp Lys Pro Lys Lys Ala Gly Asn Val
115 120 125
Leu Ile Tyr Pro Ala Leu Ala Phe His Val Asn Ile Leu Lys Asn His
130 135 140
Ile His Ile Gly Phe His Leu Thr His Lys Phe Glu Tyr Asn Tyr Thr
145 150 155 160
Leu Gln Gln Met Ile Glu Arg Gly Glu Ile Ile Asn Pro Gly Leu Lys
165 170 175
Val Val His Ser Asp Val Arg Asn Asn Tyr Thr Tyr Glu Val Glu Gln
180 185 190
Val Ala Pro Tyr Ser Val Met Glu Thr Cys Gln Lys Leu Lys Lys Ser
195 200 205
Ile Tyr Gln Tyr Tyr Leu Asp Lys Gly Asn Met Lys Ile Val Asp Thr
210 215 220
Leu His Glu Asn Val Lys Val Ile Tyr Ala Lys Pro Ile Asn Gly Gly
225 230 235 240
Asp Ser Leu Ser Tyr Ala Ala Thr Ile Leu Lys Pro Met Cys Ser Phe
245 250 255
Glu Thr Met Gln Pro Phe Glu Thr Lys Lys Val Met Asp Ile Leu Lys
260 265 270
Met Asn Pro Asn Asp Arg Met Lys Lys Gln Leu Arg Gln Ala Lys Asp
275 280 285
Leu Leu Asn Val Tyr Pro Tyr Leu Lys Phe Glu His Asn Pro Phe Leu
290 295 300
Ile Glu Leu Asn Asn Tyr Gln Leu Val Gln Leu Thr Asp Pro Lys Ile
305 310 315 320
Leu Met Asp Gln Lys Tyr Val Lys Pro Leu His Gly Leu Lys Asn Gly
325 330 335
Lys Leu Tyr Lys Gly Gly Ser Val Lys Leu Ser Ile Phe Met Asp Glu
340 345 350
Thr Met Glu Thr Ser Leu Gly Ile Ser Lys Lys Leu Val Tyr Arg Phe
355 360 365
Ile Lys Val Leu Gln Gln Ile Ala Glu Gln His Gly Val Val Ile Glu
370 375 380
Ile Asn Tyr Ala Thr Ser Ser Ile Lys Gly Lys Phe Thr Glu Glu Phe
385 390 395 400
Phe Gln Gln Phe Ser Trp Glu Ile Arg Glu Leu Glu Ser Ile Phe Thr
405 410 415
Asn Thr Thr Val Leu Ala Val Ile Thr Asp Glu His Leu Thr Lys Leu
420 425 430
Pro Val Lys Val Tyr Asp Ala Phe Lys Arg Gln Phe Gly Gly Lys Trp
435 440 445
Asp Ile Ser Ser Gln Val Ile Thr Glu Lys Ser Leu Lys Ser Phe Gln
450 455 460
Gln Leu Leu Lys Ile Arg Lys Leu Glu Glu Phe Asp Leu Asn Asp Glu
465 470 475 480
Lys Leu Cys Gln Gln Val Ala Asn Ile Val Lys Tyr Asp Asn Leu Ser
485 490 495
Tyr Thr Ile Phe Asn Ile Leu Leu Gly Ile Tyr Val Lys Ser Gly Met
500 505 510
Gln Pro Trp Ile Leu Ala Glu Arg Thr His Ser Asp Cys Phe Ile Gly
515 520 525
Leu Asp Val Ser His Glu Asp Gly Lys Ser Thr Ala Gly Ile Met Asn
530 535 540
Val Ile Gly Ser Asn Gly Tyr Leu Leu Lys Gln Ser Ala Ile Asn Gly
545 550 555 560
Val Leu Ala Gly Glu Lys Ile Asp Thr Glu Lys Leu Glu Glu Ile Ile
565 570 575
Gln Asp Val Ile Phe Thr Tyr Lys Glu Gln Phe Gly Lys Leu Pro Arg
580 585 590
His Val Thr Ile His Arg Asp Gly Arg Trp Arg Glu Asp Ser Val Leu
595 600 605
Val Ala Gln Ile Phe Lys Asp Arg Gly Ile Thr Tyr Asp Ile Val Glu
610 615 620
Val Ile Lys Lys Pro Asn Arg Arg Met Ala Phe Tyr Asn Lys Lys Thr
625 630 635 640
Asp Gln Tyr Glu Thr Lys Gln Gly Val Tyr Tyr Ile Arg Asp Asn Glu
645 650 655
Ala Phe Leu Cys Ala Thr Asp Pro Arg Arg Asn Ile Gly Met Ala Gln
660 665 670
Pro Ile Lys Ile Val His Gln Thr Asp Thr Leu Ala Phe Gln Gln Ile
675 680 685
Ile Glu Asp Ile Tyr Arg Leu Ser Phe Met His Ile His Ala Leu Asn
690 695 700
Lys Met Arg Leu Pro Ala Thr Ile His Tyr Ala Asp Leu Ser Ser Thr
705 710 715 720
Ala Tyr Gln Arg Gly Gln Ile Ala Pro Arg Thr Thr Asn Val Thr His
725 730 735
Leu Pro Phe Val
740
<210> 80
<211> 795
<212> PRT
<213> artificial sequence
<400> 80
Met Lys Asp His Ile Leu Asn Leu Tyr Arg Ile Asp Asn Leu Ser Glu
1 5 10 15
Leu Asp Phe Ser Tyr Lys Leu Ile Asp Phe Asp Leu Ser Phe Ile Ala
20 25 30
Gly Lys Glu Glu Leu Leu Asn Lys Gln Leu Gln Lys Ile Ala Glu Glu
35 40 45
Val Ser Ser Val Thr Lys Gly Pro Thr Ala Val Leu Lys Arg Asn Gln
50 55 60
Arg Phe Phe Val Ala Val Pro Ala Asp Lys Gln Met Glu Asp Arg Ser
65 70 75 80
Ile Asp Gly Ile Pro Phe Ser Ile Pro Ile Lys Leu Leu Pro Glu Val
85 90 95
Tyr Arg Ile Asp Ser Lys Asp Ile Gln Gly His Gln Leu Asp Val Val
100 105 110
Tyr Lys Phe Leu Asp Tyr Glu Ile Arg Arg Gln Leu Gly Gln His Arg
115 120 125
Asp Leu Trp Lys Leu Asn Thr His Gln Phe Phe Leu Arg Glu Pro Met
130 135 140
Lys Gly Ile Gln Gly Ser Ile Asn Val Phe Glu Gly Phe Thr Tyr Lys
145 150 155 160
Leu Ala Arg Leu Ala Asp Gly His Phe Tyr Val Thr Leu Asp Leu Ser
165 170 175
Thr Lys Tyr Ile Asp Lys Tyr Cys Leu Ser His Tyr Ile Asn Glu Gly
180 185 190
Asn Val Arg Thr Phe Glu Asn Asn Tyr Lys Gly Arg Arg Phe Leu Tyr
195 200 205
Leu Asn Gly Asp Asn Trp Tyr Thr Ile Glu Leu Leu Gly Phe Gly Lys
210 215 220
Ser Val Lys Glu Gln Asp Phe Ile Arg Glu Gly Thr Thr Tyr Asn Val
225 230 235 240
Leu Asn Tyr Ile Thr Glu Lys Ile Glu His Ser Arg Thr Asp Leu Lys
245 250 255
Arg Tyr Val Lys Pro Asn Asp Leu Ser Met Ser Tyr Thr Tyr Pro Gly
260 265 270
Arg Thr Met Asp Pro His Ser Gly Ala Thr Ser Leu Ala Arg Met Leu
275 280 285
Tyr Asn Thr Lys Asp Glu Arg Val Lys Ser Leu His Tyr Leu Ser Ile
290 295 300
Lys Gly Pro Ser Lys Arg Phe Glu Ala Ile Asn Asn Tyr Ile Ser Ser
305 310 315 320
Tyr Phe Lys Asn Leu Lys Phe Asn Ala Gly Lys Leu Leu Ile Ser Asn
325 330 335
Glu Pro Leu Val Glu Lys Ile Lys Asn Phe Trp Ile Pro Glu Leu Leu
340 345 350
Phe Asn Asn Asn Arg Arg Leu Lys Ile Thr Gly Phe Asn Ser Gly Met
355 360 365
Arg Asp Phe Ala Tyr Gln Arg Lys Gln Leu Ile Lys Asn Asn Gly Val
370 375 380
Leu Asn Arg Thr Ser Phe Asp Val Gln Tyr Leu Leu Val Pro Asp Glu
385 390 395 400
Gln Tyr Met Asp Ala Asn Leu Val Glu Gly Phe Lys Asn Asn Ala Glu
405 410 415
Phe Leu Ile Lys Lys Leu Ala Pro Ala Phe Asp Lys Phe Ile Ile Ile
420 425 430
Arg Tyr Pro Val Lys Ser Cys Thr Ser Ala Ser Val Gln Ile Gln Glu
435 440 445
Ile Glu Lys Val Leu His Arg Arg Asn Ala Leu His Gly Phe Ala Leu
450 455 460
Val Val Leu Pro Asp Leu Asp Ala Phe Ser Pro Ala Phe Leu Lys Thr
465 470 475 480
Phe His Glu Leu Leu Lys Ser Lys Phe Tyr Pro Asp Leu Lys Val Gln
485 490 495
Cys Ala Ser Ala His Asn Ile Ser Ser Phe Phe Lys Pro Phe Ser Thr
500 505 510
Ala Gly Asn Asn Gly Ile Val Glu Tyr Arg Val Val Glu Ala Leu Lys
515 520 525
Gly Arg Phe Ser Ser Tyr Leu Phe Tyr Leu Val Leu Glu His Leu Ile
530 535 540
Val Asn Arg Lys Trp Pro Tyr Ala Leu Ala Lys Asn Leu Phe Tyr Asp
545 550 555 560
Ile Tyr Ile Gly Ile Asp Val His Asp Arg His Ala Gly Phe Thr Phe
565 570 575
Phe Phe Lys Asn Gly Glu Gln Ile Ile Phe His Pro Glu Glu Val Pro
580 585 590
Gln Lys Thr Asn Ser Gln Arg Val Glu Lys Val Arg Ala Lys Thr Leu
595 600 605
Asn Lys Val Ile Tyr Glu Lys Leu Lys Leu Tyr Ile Pro Leu Phe Ala
610 615 620
Pro Asn Pro Asn Gly Ile Val Ile Val Arg Asp Gly Arg Ser Phe Gly
625 630 635 640
Val Glu Tyr Lys Ala Leu Gln Ala Ala Ile Asn Thr Leu Ala Ala Glu
645 650 655
Gly Ile Val Asn Lys Asp Thr Val Lys Tyr Gly Val Val Asp Leu His
660 665 670
Lys Gln Ser Ser Val Pro Ile Arg Ile Ala Ala Lys Thr Asn Ser Tyr
675 680 685
Asp Gln Leu Glu Asn Pro Val Ala Gly Ser Tyr Lys Leu Val Ser Pro
690 695 700
Lys Glu Gly Phe Ile Phe Ser Thr Gly Tyr Pro Phe Asp Ile Lys Gly
705 710 715 720
Thr Ser Arg Pro Leu Asn Leu Ser Met Lys Glu Gly Asp Leu Asp Phe
725 730 735
Met Lys Val Met Glu Asp Val Phe Cys Gln Ile Met Leu Ala Phe Ser
740 745 750
Ala Pro Asp Lys Ser Asn Phe Leu Pro Val Ile Ile Lys Leu Ile Asp
755 760 765
Thr Leu Leu Glu Pro Leu Thr Ala Thr Arg Glu Thr Ala Asp Glu Ala
770 775 780
Glu Glu Asp Glu Glu Glu Met Met Asp Ile Asn
785 790 795
<210> 81
<211> 731
<212> PRT
<213> artificial sequence
<400> 81
Met Gly Arg Phe Ile Asn Ser Phe Glu Ile Asp Val Pro Ser Val Thr
1 5 10 15
Ala Asp Leu Tyr Asp Ile Asp Pro Gln Pro Asn Asp Asn Tyr Ser Leu
20 25 30
Leu Asn Ala His Ala Thr Ile Leu Glu Arg Asn Val Gly Gly Arg Ala
35 40 45
Arg Trp Tyr Asn Gln Gly Gly Arg His Tyr Ile Ala Val Ile Gly Ala
50 55 60
Glu Arg Asp Tyr Gly Thr Ile Gln Ser Ala Asp Gly Ala Glu Leu Glu
65 70 75 80
Phe Ala His Glu Ser Asp Leu Asp Phe Ser Glu Trp Ser Asp Phe Lys
85 90 95
Val Leu Gln Glu Ala Leu Ile Asp Glu Leu Lys Asp Asp Leu Glu Thr
100 105 110
Asp Asp Tyr Trp Tyr Asp Ser Thr Lys Asn Thr Phe Tyr His Glu Asp
115 120 125
Arg Glu Ala Arg Ile Glu Gly Tyr Asp Val His Pro Gly Val Glu Val
130 135 140
Arg Ile Ser His His Asp Arg Pro Leu Ile Thr Leu Asp Pro Thr Leu
145 150 155 160
Gly Ala Phe Gly Ser Arg Thr Leu Ala Asp Tyr Leu Asn Asp Pro Ala
165 170 175
Trp Gly Ile Asp Arg Val Asn Asp Glu Leu Val Gly Arg Thr Phe Ile
180 185 190
Tyr Gln Thr Ser Asp Arg Ala Ser Cys Thr Val Thr Gly Val Phe Glu
195 200 205
Asn Thr Thr Val Ser Glu Ile Pro Pro Gly Arg Phe Asp Asn Glu Thr
210 215 220
Leu Asp Glu Ile Glu Ser Arg His Gly Lys Glu Tyr Ala Asp Arg Ile
225 230 235 240
Asp Pro Ser Glu Pro Thr Val Lys Ile Gln Tyr Gly Asn Ser Asp Trp
245 250 255
Tyr Pro Ala Ala Pro Ser Leu Leu Leu Phe Ala Pro Ser Glu Asp Arg
260 265 270
Pro Asp Glu Ile Ser Gln Arg Ala Thr Phe Gly Pro Gln Glu Arg Trp
275 280 285
Gln Lys Val Glu Asp Phe Arg Glu Leu Ile Gly Asp Ile Ser Ile Gly
290 295 300
Ser Ile Gln Thr Asp Ile Ser Pro Ser Pro Val Arg Asp Gly Ile Ser
305 310 315 320
Ala Tyr Gly Tyr Pro Val Leu Thr Phe Gly Asp Asp Pro Ser Thr Glu
325 330 335
Met Ala Ile Gly Arg Pro Asn Ile Ser Phe Asn Gly Ser Glu Leu Thr
340 345 350
Gln Glu Tyr Trp Asn Pro Ala Lys Gln Gly Tyr Leu Glu Glu Val Gly
355 360 365
Pro Arg Arg Thr Phe Asp Gln Asp Phe Ser Val Ala Val Leu Phe Pro
370 375 380
Glu Gly Thr Glu Asp Glu Ala Leu Ser Ala Tyr Gln Gln Val Arg Glu
385 390 395 400
Tyr Val Glu Glu His Leu Gly Leu Ile Leu Ser Asp Arg Pro Gly Arg
405 410 415
Val Asn Tyr Glu Asp Pro Arg Glu Val Glu Glu Trp Gln Arg Ser Leu
420 425 430
Glu Asp Val Asp Ala Gly Phe Gly Tyr Leu Pro Glu Tyr Asp Glu Asp
435 440 445
Val Tyr His Lys Leu Ile Glu Ile Leu Glu Gly Lys Pro Leu Gln Ser
450 455 460
Leu Thr Ala Thr Asn Leu Arg Ser Ala Gln Arg Ser Gly His Glu Ala
465 470 475 480
Asp Val Ile Ser Asn Thr Ala Val Gly Leu Gly Val Lys Leu Gly Val
485 490 495
Ile Pro Phe Ser Ile Glu Asn Gln Leu Asp Thr Asp Ala Tyr Leu Gly
500 505 510
Leu Ser Val Thr Gly Arg Asp Arg Thr Val Ala Ser Gly Val Val Val
515 520 525
Ser Gly Thr Asp Asn Gln Ile Leu Tyr Gln Thr Glu Glu Thr Asn Pro
530 535 540
Thr Gly Arg Ser Thr Val Thr Asn Gln Gly Met Thr Lys Gln Ile Leu
545 550 555 560
Ile Arg Ala Val Gln Gly Ala Val Asn Asp Pro Arg Ser Gly Phe Asp
565 570 575
Gln Leu Ser Ser Leu Thr Ile His Arg Asn Gly Tyr Leu Gly Asp Asp
580 585 590
Glu Ile Ser Gly Leu Lys Glu Gly Val Glu Tyr Leu Lys Ser Asn Asp
595 600 605
Phe Val Thr Glu Ser Phe Glu Trp Val Gly Val Asp Val Gln His Ser
610 615 620
Pro Thr Tyr Arg Ile Tyr Asp Asp Asp Gly Met Pro Asp Met Gly Ser
625 630 635 640
Tyr Ala Gln Leu Asp Asp Glu Thr Val Leu Ile Val Thr Thr Asp Ala
645 650 655
Pro Arg Leu Gly Glu Gly Thr Pro Gln Pro Ile Leu Cys Glu Ile Ser
660 665 670
Val Glu Glu Gly Asp Phe Asp Ile Tyr Ser Val Gly Arg Asp Ala Phe
675 680 685
Tyr Leu Ser Glu Leu Asn Trp Gly Ala Pro Ser Lys Gly Ile Lys Asp
690 695 700
Pro Leu Thr Val Tyr Leu Thr Arg Arg Met Asn Ser Arg Leu Ser His
705 710 715 720
Asp Arg Val Ser Arg Leu Thr Tyr Pro Pro Phe
725 730
<210> 82
<211> 728
<212> PRT
<213> artificial sequence
<400> 82
Met Ala Tyr Ser Leu Asn Ala Phe Glu Leu Glu Ile Pro Asp Ile Asp
1 5 10 15
Ala Asp Leu Tyr Lys Val Asp Pro Gln Pro Ser Asp Asp Pro Tyr Arg
20 25 30
Ile Leu Gly Gly Leu Glu Arg Ser Phe Glu Gln Gln Leu Asp Gly Lys
35 40 45
Ala Gln Lys Trp Lys Gln Ala Glu Asp Gly Asp Trp Tyr Ile Ala Val
50 55 60
Ile Gly Ala Ser Glu Arg Lys Thr Ile Glu Ser Pro Ser Ser Gly Thr
65 70 75 80
Arg Ala Gly Tyr Thr Thr Thr His Thr Leu Asp Pro Ser Ser Phe Trp
85 90 95
Asp Arg Met Val Leu Gln Arg Ala Ile Ser Asp Ser Val Arg Trp Tyr
100 105 110
Met Thr Asn Tyr Gln Asp Phe Trp Tyr His Glu Asp Ala Asp Ala Leu
115 120 125
Phe Tyr Pro Ser Pro Arg Gly Lys Val Asp Glu Tyr Asp Val Tyr Thr
130 135 140
Gly Phe Ser His Arg Val Glu Phe Tyr Asp Ser Pro Gln Leu Val Val
145 150 155 160
Arg Ser Val Thr Lys Phe Ile Ser Ser Glu Ser Leu Ala Asp Arg Ile
165 170 175
Asn His Gln Gly Thr Glu Glu Ala Thr Glu Lys Tyr Gly Gly Glu Asn
180 185 190
Phe Arg Leu Asp Arg Pro Glu Pro Thr Lys Cys Thr Leu His Gly Ile
195 200 205
Ser Thr Glu Arg Thr Val Ser Asp Lys Thr Ile Asp Phe Gly Asp Glu
210 215 220
Met Leu Ser Val Leu Glu Phe Ala Gln Arg Lys Tyr Gly Ser Glu Trp
225 230 235 240
Ala Asp Lys Ile Asp Pro Asp Glu Pro Leu Val Gln Ile Arg Phe Gly
245 250 255
Asn Ser Asp Pro Tyr Asp Thr Ala Pro Ser Leu Leu Asn Ala Ser Pro
260 265 270
Glu Glu Leu Asn Arg Arg Leu Thr Ser Glu Ala Ala Leu Ser Ala Gln
275 280 285
Glu Arg Gln Lys Ala Ile Gln Asn Phe Ile Gly Arg Ile His Tyr Ile
290 295 300
Gln Val Glu Asp Glu Lys Val Ser Val Ser Asp Asp Gly Val Arg Pro
305 310 315 320
Thr Glu Gln Gly Asp Phe Asp Tyr Pro Asp Leu Ala Phe Gly Asn Asp
325 330 335
Glu Val Leu Ser Thr Gly Val Pro Asn Ala Val Asp Pro Ser Gln Glu
340 345 350
Val His Pro Gly Asn Trp Arg Trp Ile Ile Arg Asp Tyr Leu Glu Glu
355 360 365
Tyr Gly Phe Trp Glu Ser Gln Arg Lys Leu Ser Glu Ile Val Leu Val
370 375 380
Tyr Pro Arg Gly Glu Glu Arg Arg Ala Glu Asn Leu Tyr Gln Asp Val
385 390 395 400
Arg Glu Lys Leu Ser Glu Ile Gly Gly Val Gln Ile Arg Ser Asp Pro
405 410 415
His Arg Val Cys Tyr Thr Asp Gln Val Glu Phe Asp Glu Trp Val Ala
420 425 430
Glu Phe Gly Asp Ser Ile Asp Gly Val Leu Gly Leu Ile Glu Gly Asp
435 440 445
Gly Asp Glu Tyr Tyr Glu Ile Ile Asp Ala Phe Gly Gly Ala Pro Thr
450 455 460
Gln Tyr Val Asn Thr Ser Thr Tyr Ser Glu His Arg Gly Ala Ser Asp
465 470 475 480
Asp Val Ile Phe Asn Thr Ala Cys Gly Leu Ala Val Lys Leu Gly Ala
485 490 495
Tyr Pro Phe Gly Leu Ala Asn Asp Leu Asn Ser Asp Val Tyr Leu Gly
500 505 510
Leu Ser Val Ala Gly Asp Arg Ser Thr Thr Ala Thr Ala Val Ala Ile
515 520 525
Asp Gly Arg Asp Gly Arg Ile Leu Tyr Gln Thr Glu Glu Pro Leu Gly
530 535 540
Gln Gly Ser Ser Thr Val Ser Glu Gly Tyr Pro Ala Lys Arg Ile Ile
545 550 555 560
Gln Arg Ser Leu Lys Thr Ala Ser Ser Ala Phe Asp Arg Pro Ile Glu
565 570 575
Ser Phe Asp Ile His Arg Asn Gly Asp Phe Gly Asp Ala Glu Leu Glu
580 585 590
Thr Leu Ser Ser Glu Leu Pro Ala Leu Gln Asp Gln Glu Tyr Val His
595 600 605
Thr Asp Val Ser Trp Ser Ala Val Glu Val Ile Glu Asn His Pro Tyr
610 615 620
Arg Leu Phe Ser Glu Arg Gly Ser Arg Ala Pro Asp Thr Gly Ala Tyr
625 630 635 640
Ala Lys Leu Asp Asp Glu His Val Leu Val Thr Thr Phe Gly Glu Pro
645 650 655
Gln Ile His Gln Gly Thr Pro Lys Pro Val Leu Cys Lys Arg Arg Ala
660 665 670
Thr Ser Gln Asp Gln Asp Ile Thr Ala Ile Gly Glu Asp Val Phe Lys
675 680 685
Leu Ser Phe Leu Asn Trp Gly Ser Pro Met Met Lys Met Lys Pro Pro
690 695 700
Val Thr Thr Lys Ile Pro Lys Glu Leu Asn Glu Ile Phe Glu Lys Cys
705 710 715 720
Ser Arg Val Arg Tyr Pro Pro Phe
725
<210> 83
<211> 737
<212> PRT
<213> artificial sequence
<400> 83
Met Gly Leu Phe Val Asn Ser Phe Glu Ile Glu Leu Pro Ala Ile Glu
1 5 10 15
Ala Asp Leu Tyr Ser Ile Asp Pro Gln Pro Ser Gly Asp Lys Tyr Ser
20 25 30
Val Leu Asn Ser His Thr Glu Asp Leu Glu Asp Thr Val Gly Gly Lys
35 40 45
Gly Arg Trp Tyr Arg Arg Gly Asp Glu Tyr Phe Ile Ala Ile Val Gly
50 55 60
Ser Asp Arg Arg Glu Tyr Asp Thr Phe His Ser Ala Gly Ala Glu Leu
65 70 75 80
Ser Phe Glu Glu Thr Ala Glu Leu Asp Pro Thr Thr Glu Ala Gly Phe
85 90 95
Gly Val Ile Glu Arg Ala Leu Thr Lys Gly Leu Gln Trp Tyr Leu Glu
100 105 110
Thr Tyr His Gly Tyr Trp Tyr Asp Ser Val Arg Asn Ala Phe Tyr Glu
115 120 125
Glu Glu Val Leu Asp Thr Val Glu Gly Tyr Asp Leu His Ser Gly Ile
130 135 140
Asp Val Arg Phe Gly Tyr His Gly Arg Pro Val Phe Thr Leu Asp Ser
145 150 155 160
Thr Ile Gly Leu Met Gly Lys Gln Thr Leu Ala Glu Tyr Leu Ser Glu
165 170 175
Trp Gly Leu Glu Arg Thr Gln Ala Glu Phe Ile Gly Glu Gly Phe Met
180 185 190
Gln Asp Gly Pro Glu Arg Arg Ser Cys Thr Leu Asp Gly Ile Tyr Ser
195 200 205
Asp Ile Thr Val Glu Asp Pro Ser Pro Asp Pro Trp Asp Asp Ser Val
210 215 220
Leu Gln Phe Ile Lys Glu Glu Tyr Cys Gln Gln Trp Ala Glu Arg Val
225 230 235 240
Asp Pro Thr Glu Pro Leu Ala Lys Ile Arg Tyr Asn Arg Arg Asp Lys
245 250 255
Trp Tyr Pro Ala Ala Pro Ser Leu Leu Tyr Pro Ser Pro Gly Asp Asp
260 265 270
Arg Pro Asp Ser Ile Ser Glu Arg Ala Ala Lys Ala Pro Val Asp Arg
275 280 285
Trp Asp Asp Val Gly Thr Phe Leu Asp Ile Ile Gly His Ile Gln Met
290 295 300
Gly Asn Val Glu Ala Pro Val Thr Gln Ser Pro Ile Gln Ala Gly Ile
305 310 315 320
Gly Thr Phe Asp Tyr Pro Val Leu Thr Phe Gly Gln Asp Pro Arg Thr
325 330 335
Glu Met Glu Leu His Gln Pro Asn Ile Ser Leu Asn His Ser Pro Asp
340 345 350
Leu Lys Pro Gln Tyr Trp Asn Pro Ala Lys Glu Gly Tyr Leu Glu Glu
355 360 365
Val Gly Pro Arg Val Ser Phe Asp Asp Glu Ile Gln Val Ala Val Phe
370 375 380
Tyr Ala Asp Gly Asp Glu Ser Glu Ala Leu Asp Val Tyr Asp Asp Ile
385 390 395 400
Arg Glu Tyr Ala Glu Arg Phe Thr Gly Ile Asn Leu Ser Glu Arg Val
405 410 415
Gly Arg Ile Asn Phe Asp Asp Glu Arg Leu Leu Asp Glu Phe Glu Asp
420 425 430
Lys Thr Arg Gln Asn Ile Asp Ala Gly Phe Ala Tyr Leu Pro Glu Tyr
435 440 445
Asp Glu Glu Thr Tyr His Arg Leu Ile Asp Ile Leu Asp Gly Arg Pro
450 455 460
Leu Gln Ser Leu Thr Ala Thr Lys Leu Arg Ser Lys Arg Arg Ser Gly
465 470 475 480
Asn Glu Ala Asp Val Leu Thr Asn Thr Ala Ile Gly Leu Gly Val Lys
485 490 495
Leu Gly Val Val Pro Phe Thr Ile Glu Asp Gln Leu Ser Ala Asp Ala
500 505 510
Tyr Leu Gly Met Ser Val Thr Gly Tyr Glu Thr Lys Thr Ala Ser Val
515 520 525
Val Leu Ile Ser Gly Lys Asn Gly Arg Ile Val Tyr Gln Ser Gln Asp
530 535 540
Pro Arg Pro Ser Asn Arg Ser Thr Val Thr Asn Glu Gly Ile Met Gln
545 550 555 560
Glu Phe Leu Lys Asp Ala Val Arg Ala Ala Asn Asp Ser Pro His Ile
565 570 575
Pro Gly Asp Thr Leu Asp Ser Leu Val Ala His Arg Asn Gly Phe Phe
580 585 590
Gly Lys Lys Glu Ile Lys Gly Leu Tyr Glu Gly Ile Glu Arg Leu Gln
595 600 605
Glu Tyr Ser Tyr Val Thr Asp Ser Phe Asn Trp Val Gly Val Asp Val
610 615 620
Met Gly Asn Thr Pro His Arg Ile Phe Asp Asp Ser Arg Asn Asp Leu
625 630 635 640
Met Pro Asp Met Gly Ala Tyr Ala Ala Leu Asp Asp Glu Thr Val Thr
645 650 655
Val Val Thr Thr Asp Ala Pro Arg Leu Gly Gln Gly Ser Pro Lys Pro
660 665 670
Leu Tyr Cys Glu Val Thr Ala Ser Gly Gly Pro Phe Asp Ile Arg Asp
675 680 685
Ile Gly Arg Asp Ile Phe Tyr Leu Ser Glu Leu Asn Trp Ala Ala Pro
690 695 700
Ser Lys Gly Ile Lys Asn Pro Leu Thr Val Tyr Leu Thr Arg Arg Met
705 710 715 720
Asn Arg Arg Leu Ser His Asp Arg Val Ser Lys Leu Ala Tyr Pro Pro
725 730 735
Phe
<210> 84
<211> 732
<212> PRT
<213> artificial sequence
<400> 84
Met Ala Leu Phe Ala Asn Ser Phe Glu Ile Glu Val Pro Lys Leu Ser
1 5 10 15
Ala Ala Lys Tyr Ser Ile Asp Pro Gln Pro Ser Ser Ser Asp Pro Trp
20 25 30
Lys Gln Leu Asp Asn Tyr Glu Arg Ala Ile Lys Ser Glu Cys Ser Gly
35 40 45
Ser Ala Gln Arg Ile Asn Glu Asp Gly Lys Trp Tyr Ile Leu Ser Ile
50 55 60
Gly Ser His Asp Ser Lys Pro Ser Val Thr Thr Asn Asp Gly Thr Glu
65 70 75 80
Leu Thr Lys Ile Gly Asp Thr Thr Val Gly Gly Glu Ser Gly Lys Tyr
85 90 95
Gln Glu Ala Val Ile Gln Ser Leu Arg Asp Ser Leu Gly Trp Phe Val
100 105 110
Thr Thr Gln Leu Asp Tyr Trp Glu Leu Gly Asn Ser Gln Arg Phe Tyr
115 120 125
Glu Trp Asn Pro Ser Asp Ile Val Asp Gly Tyr Asp Thr Tyr His Gly
130 135 140
Tyr Ser Thr Ser Ile Glu Phe Asn Asp Gly Tyr Tyr Leu Thr Ile Asp
145 150 155 160
Pro Thr Val Lys Phe Ile Ser Asp Leu Ser Val Tyr Asp Tyr Leu Lys
165 170 175
Lys Phe Gly Ser Lys Lys Val Glu Asn Leu Leu Leu Asp Arg Asn Cys
180 185 190
Thr Leu Met Ser Asn Asp Arg His Thr Val Glu Leu Val Ser Ile Ala
195 200 205
Asp Asp Leu Ser Val Ser Asp Lys Thr Met Thr Leu Asp Gly Glu Asp
210 215 220
Thr Ser Val Tyr Glu Tyr Ile Gln Asn Asn Asp Asn Tyr Ser Asp Glu
225 230 235 240
Gln Ala Glu Arg Val Asp Pro Ser Glu Pro Leu Ala Arg Ile Gln Phe
245 250 255
Tyr Trp Ser Asp Glu Pro Val Asp Ser Ala Pro Ser Leu Leu His Pro
260 265 270
His Pro Glu Glu Ile Glu Pro Ser Met Thr Gly Tyr Ala Ser Arg Ser
275 280 285
Ser Arg Ser Arg Trp Gly Asp Thr Glu Arg Phe Ala Gln Asp Ile Asn
290 295 300
Tyr Ile Gln Val Phe Asn Thr Lys Cys Pro Val Ser Asp Ser Pro Arg
305 310 315 320
Gln Asp Gly Ser Phe Ser Leu Asn Tyr Pro Pro Leu Gln Phe Gly Gly
325 330 335
Gly Asn Glu Met Val Pro Gly Gln Asn Asn Ala Ile Glu Pro Asp Gln
340 345 350
Ile Ile His Glu Arg Asn Trp Arg Tyr Val Leu Arg Asp Tyr Leu Glu
355 360 365
Glu Phe Gly Pro Val Ser Lys His Arg Gly Ala Ala Gln Ile Asp Leu
370 375 380
Leu His Pro Asp Gly Arg Glu Asp Thr Ala Leu Glu Met Phe Asp Lys
385 390 395 400
Leu Gln Ser Tyr Ala Asn Glu Tyr Val Gly Ile Thr Ile Gln Asp Arg
405 410 415
Pro Gly Thr Val Ser His Gln Asp Tyr Gln Glu Leu Arg Glu Trp Ile
420 425 430
Arg Arg His Arg Ser Asn Ser Asp Gly Val Ile Val Leu Leu Asp Ser
435 440 445
His Ser Glu Glu Tyr His Asp Ile Leu Ala Glu Leu Asp Gly Leu Pro
450 455 460
Ala Gln Ala Ile Gln Leu Lys Thr Tyr Arg Glu Ser Phe Gly Ser Asp
465 470 475 480
Gly Phe Ser Asn Ser Leu Tyr Asn Val Val Cys Gly Leu Ala Thr Lys
485 490 495
Ile Gly Thr Arg Pro Phe Leu Leu Ser Ser Pro Leu Glu Ala Asp Leu
500 505 510
Tyr Leu Gly Met Ser Val Thr Gly Asp Glu Val Asn Ser Ala Ala Ala
515 520 525
Val Leu Ile Ser Gly Ser Asn Gly Asp Leu Ile His Gln Thr Thr Asn
530 535 540
Asn Leu Ala Thr Gly Ser Ser Thr Val Thr Asn Phe Glu Val Ser Arg
545 550 555 560
Arg Ile Val Arg Gln Leu Ile Ala Glu Ala Ile Asp Arg Gly Leu Ile
565 570 575
Glu Asp Pro Gln Ser Leu Ile Ile His Arg Asn Gly Gln Phe Gly Asp
580 585 590
Ala Glu Ile Asp Gly Ile Arg Asp Gly Ile Ser Glu Leu Gln Asp Ser
595 600 605
Gly His Ile Asn Gly Ser Phe Asp Trp Gln Ala Ile Glu Ile Ser Glu
610 615 620
Ser Ser Gly His Arg Leu Tyr Ser Asp Thr Gly Asn Arg Thr Cys Glu
625 630 635 640
Thr Gly Ala Ala Met Arg Leu Asp Ser Gln Asn Val Ile Val Ser Thr
645 650 655
Tyr Gly Lys Pro Glu Ile His Gln Gly Ser Pro Ser Pro Leu His Cys
660 665 670
Ser Val Ser Val Asp Asn Gly Asp Ile Ser Val Glu Gly Ile Ala Ser
675 680 685
Asp Val Phe Lys Leu Ser Phe Leu Asn Trp Gly Ser Pro Met Met Lys
690 695 700
Met Lys His Pro Leu Thr Thr Gln Leu Pro Ser Gln Met His Asp Ile
705 710 715 720
Leu Ser Ser Gly Ile Pro Leu Ser Tyr Pro Pro Phe
725 730
<210> 85
<211> 484
<212> PRT
<213> artificial sequence
<400> 85
Met Lys Phe Glu Thr Lys Ile Phe Glu Glu Pro Gln Leu Glu Phe Gly
1 5 10 15
Asp Lys His His His Pro Asp Pro Arg Leu Gly Leu Ser Glu Ala Gly
20 25 30
Pro Leu Gln Ile Pro Leu Gly Asp Val Val Lys Ile Ala Val Ile Gly
35 40 45
Ser Ser Lys Thr Val Glu Asp Thr Lys Glu Phe Phe Glu Glu Ala Val
50 55 60
Ala Gly Phe Glu Gly Lys Gly Glu Lys His Pro Asn Leu His Pro Asp
65 70 75 80
Phe Pro Gly Leu Gly Asn Gln Asn Pro Tyr Arg Cys Lys Phe Glu Ile
85 90 95
Ser Asp Gly Ala Thr Ile Ala Ile Ser Gln Ser Lys Ile Asp Lys Ile
100 105 110
Arg Lys Glu Pro His His Tyr Lys Ala Val Glu Met Ala Val Asp Glu
115 120 125
Ile Val Gln Gln Leu Gln Thr Leu Asp Glu Thr Ser His Arg Pro Asp
130 135 140
Val Ala Ile Val Ala Leu Pro Val Glu Leu Ile Glu Arg Val Trp Asn
145 150 155 160
Ala Lys Val Asp Ser Lys Ala Thr Thr Glu Lys Asp Asp Ser Gly Gly
165 170 175
Ser Asp Ala Pro Asp Phe Arg Gly Met Leu Lys Ala Lys Ala Met Asp
180 185 190
Leu Ser Phe Pro Ile Gln Ile Ala Trp Glu Asp Val Phe Asp Glu Ser
195 200 205
Ala Lys Ile Pro Leu Lys Val Lys Glu Ser Arg Ala Arg Lys Ile Gln
210 215 220
Asp Gln Ala Asp Arg Thr Trp Asn Leu Leu Thr Thr Ile Tyr Tyr Lys
225 230 235 240
Gly Thr Gly Arg Ile Pro Trp Arg Lys Met Pro Gln Asp Gly Glu Phe
245 250 255
Thr Ala Cys Tyr Ile Gly Ile Ser Phe Tyr Arg Glu Val Gly Gly Gln
260 265 270
Gln Leu Phe Thr Ser Ala Ala Gln Met Phe Asp Glu Arg Gly Arg Gly
275 280 285
Phe Ile Leu Lys Gly Lys Arg Ala Gln Thr Glu Ser Arg Gly Arg His
290 295 300
Pro Tyr Met Thr Gln Glu Asp Ala His Glu Leu Val Ala Asn Ala Leu
305 310 315 320
Thr Ala Tyr Lys Asn His His Lys His Tyr Pro Ala Arg Val Ile Val
325 330 335
Leu Lys Thr Ser Lys Phe Arg Glu Glu Glu Ala Glu Gly Ile Phe Glu
340 345 350
Ala Ile Asn Glu Ala Gly Leu Glu Phe Arg Asp Leu Val Trp Val Gln
355 360 365
Glu Ser Tyr Ser Val Lys Val Leu Arg Asp Gly Asn Tyr Pro Val Met
370 375 380
Arg Gly Thr Phe Val Asp Leu Asp Gly Lys Gly Leu Leu Tyr Thr Asn
385 390 395 400
Gly Ser Ile Pro Tyr Tyr Gly Thr Tyr Pro Gly Met Tyr Asp Pro Arg
405 410 415
Pro Leu Leu Leu Cys Pro Tyr Glu Gly Ser Asp Ser Thr Val Ala Gln
420 425 430
Ile Ala Ser Glu Val Leu Ala Leu Thr Lys Val Asn Trp Asn Ser Thr
435 440 445
Gln Met Asn Gln Lys Leu Pro Ile Pro Ile Arg Ala Ala Arg Ala Val
450 455 460
Gly Glu Val Leu Lys Tyr Thr Thr Asp Gln Lys Val Ser Ser Asp Tyr
465 470 475 480
Ala Arg Tyr Ile
<210> 86
<211> 484
<212> PRT
<213> artificial sequence
<400> 86
Met Lys Phe Glu Thr Lys Ile Phe Asp Glu Pro His Leu Glu Phe Gly
1 5 10 15
Asn Asn His His His Pro Asp Pro Arg Leu Gly Leu Phe Glu Ala Gly
20 25 30
Pro Leu Gln Ile Pro Leu Gly Asp Val Val His Ile Ala Ile Val Gly
35 40 45
Asp Ser Lys Thr Val Glu Asp Thr Lys Ala Phe Phe Val Asn Ala Ala
50 55 60
Thr Gly Phe Lys Gly Lys Gly Glu Lys His Pro Asn Leu His Pro Asp
65 70 75 80
Phe Pro Gly Leu Gly Asn Gln Asn Pro Phe Arg Cys Lys Phe Glu Ile
85 90 95
Ala Glu Gly Ala Thr Ala Ala Ile Ser Gln Ser Lys Ile Asp Lys Ile
100 105 110
Arg Lys Glu Pro Asn His Gly Lys Ala Val Glu Met Ala Val Asp Glu
115 120 125
Ile Val Gln Gln Leu Gln Thr Leu Asp Asp Gly Ser His Arg Pro His
130 135 140
Val Ala Ile Val Ala Leu Pro Val Ser Leu Ile Glu Arg Val Trp Asn
145 150 155 160
Ala Lys Val Asp Ser Lys Ala Thr Val Glu Lys Asp Asp Ser Gly Gly
165 170 175
Ser Asp Ala Pro Asp Phe Arg Gly Met Leu Lys Ala Lys Ala Met Gly
180 185 190
Leu Ser Phe Pro Ile Gln Ile Val Trp Glu Asp Val Phe Asp Glu Ala
195 200 205
Ala Lys Ile Pro Arg Lys Ile Lys Glu Asn Arg Ala Arg Lys Ile Gln
210 215 220
Asp Gln Ala Gly Arg Thr Trp Asn Leu Leu Thr Thr Leu Tyr Tyr Lys
225 230 235 240
Gly Thr Gly Arg Ile Pro Trp Arg Lys Met Pro His Asp Gly Glu Phe
245 250 255
Thr Ala Cys Tyr Ile Gly Val Ser Phe Tyr Arg Glu Val Gly Gly Gln
260 265 270
Gln Leu Phe Thr Ser Ala Ala Gln Met Phe Asp Glu Arg Gly Arg Gly
275 280 285
Phe Ile Leu Lys Gly Arg Arg Ala Phe Thr Glu Ser Arg Gly Arg His
290 295 300
Pro Tyr Met Thr Lys Ala Asp Ala Cys Gln Leu Ile Arg Asn Ala Leu
305 310 315 320
Ala Ala Tyr Lys Asn His His Lys Asn Tyr Pro Ala Arg Val Ile Val
325 330 335
Leu Lys Thr Ser Gln Phe Arg Glu Glu Glu Ala Asp Gly Ile Leu Glu
340 345 350
Ala Leu Asp Glu Ala Gly Ala Glu Leu Arg Asp Leu Val Trp Val Gln
355 360 365
Glu Ser Tyr Ser Val Lys Ile Leu Arg Asp Gly Asn Tyr Pro Val Met
370 375 380
Arg Gly Thr Phe Val Asp Leu Gly Gly Lys Gly Leu Leu Tyr Thr Asn
385 390 395 400
Gly Ser Ile Pro Tyr Tyr Gly Thr Tyr Pro Gly Met Tyr Asp Pro Arg
405 410 415
Pro Leu Leu Leu Cys Pro Tyr Lys Gly Ser Asp Ser Thr Ile Ala Gln
420 425 430
Ile Ala Ser Glu Val Leu Ala Leu Thr Lys Ile Asn Trp Asn Ser Thr
435 440 445
Gln Ile Asn Gln Lys Leu Pro Ile Pro Ile Arg Ala Ala Arg Ala Val
450 455 460
Gly Glu Val Leu Lys Tyr Val Thr Asp Glu Lys Ile Ser Ser Asp Tyr
465 470 475 480
Ala Arg Tyr Ile
<210> 87
<211> 484
<212> PRT
<213> artificial sequence
<400> 87
Met Lys Phe Thr Ser Thr Ile Phe Lys Glu Pro Gln Leu Glu Phe Gly
1 5 10 15
Asp Lys His Gln Asp Pro Asp Pro Arg Arg Gly Leu Phe Leu Ala Gly
20 25 30
Pro Leu Gln Thr Ala Ser Gly Asp Ala Ile Lys Ile Ala Val Val Gly
35 40 45
Ser Ala Lys Thr Val Glu Asp Thr Glu Lys Phe Leu Val Ala Ala Ser
50 55 60
Val Gly Phe Met Gly Lys Ser Glu Lys His Pro Asn Met His Pro Asp
65 70 75 80
Phe Pro Gly Leu Gly Asn Gln Asn Pro Tyr Arg Cys Lys Phe Glu Ile
85 90 95
Ala Gln Asp Ala Thr Ala Ala Ile Pro Gln Ala Lys Ile Glu Lys Ile
100 105 110
Arg Lys Glu Pro His His Gly Lys Ala Val Glu Met Ala Val Asp Glu
115 120 125
Val Met Gln Leu Leu Thr Ala Ile Glu Glu Gly Ser Ser Arg Pro Asp
130 135 140
Val Ala Ile Val Ala Leu Pro Val Ala Leu Ile Glu Arg Val Trp Asn
145 150 155 160
Ala Lys Val Asp Ser Asp Gly Thr Val Glu Lys Glu Asp Asp Gly Gly
165 170 175
Ser Asp Ala Pro Asn Phe Arg Gly Leu Leu Lys Ala Arg Ala Met His
180 185 190
Leu Arg Phe Pro Ile Gln Ile Val Trp Glu Asp Val Leu Asp Glu Arg
195 200 205
Ala Val Ile Pro Arg Lys Val Lys Glu Ser Ser Ala Arg Lys Ile Gln
210 215 220
Asp Glu Ala Gly Arg Ser Trp Asn Ile Met Thr Ser Leu Tyr Tyr Lys
225 230 235 240
Gly Ser Gly Arg Ile Pro Trp Arg Arg Met Pro Gln Glu Gly Glu Phe
245 250 255
Ser Ala Cys Tyr Ile Gly Ile Ser Phe Tyr Arg Glu Val Gly Gly Gln
260 265 270
Gln Leu Phe Thr Ser Ala Ala Gln Met Phe Asp Glu Arg Gly Arg Gly
275 280 285
Phe Ile Leu Lys Gly Arg Arg Ala Gln Thr Glu Thr Arg Gly Arg His
290 295 300
Pro Tyr Met Thr Gln Asp Asp Ala Arg Ala Leu Val Ala Glu Val Leu
305 310 315 320
Ala Ala Tyr Lys Asn His His Lys Asn Phe Pro Ala Arg Val Ile Val
325 330 335
Leu Lys Thr Ser Arg Phe Arg Asp Glu Glu Ala Asp Gly Ile Met Glu
340 345 350
Ala Leu Glu Glu Val Gly Thr Glu Met Lys Asp Leu Val Trp Val Gln
355 360 365
Glu Thr Ser Ser Ile Lys Val Leu Arg Asp Gly Asn Tyr Pro Val Leu
370 375 380
Arg Gly Thr Phe Val Glu Leu Asp Gly Lys Gly Leu Leu Tyr Thr Asn
385 390 395 400
Gly Ser Ile Pro Tyr Tyr Gly Thr Tyr Pro Gly Met Tyr Asp Pro Arg
405 410 415
Pro Leu Leu Leu Cys Pro His Lys Thr Ser Asp Ser Thr Val Ala Gln
420 425 430
Ile Ala Lys Glu Val Leu Ser Met Thr Lys Ile Asn Trp Asn Ser Thr
435 440 445
Gln Met Asn Gln Lys Leu Pro Ile Pro Ile Arg Ala Ala Arg Lys Val
450 455 460
Gly Glu Val Leu Lys Tyr Val Gly Asp Gly Lys Val Ser Ser Asp Tyr
465 470 475 480
Thr Arg Tyr Met
<210> 88
<211> 485
<212> PRT
<213> artificial sequence
<400> 88
Met Asp Phe Glu Ser Gln Ile Phe Glu Glu Pro Glu Leu Glu Phe Gly
1 5 10 15
Asp Lys His His His Pro Asp Pro Arg Leu Gly Leu Val Glu Ala Gly
20 25 30
Pro Leu Gln Pro Pro Leu Gly Glu Val Ile Arg Ile Ala Val Val Gly
35 40 45
Ser Ala Lys Thr Val Glu Asp Thr Lys Lys Phe Leu Ala Asp Ala Ala
50 55 60
Thr Gly Phe Gln Gly Lys Thr Glu Arg His Pro Asn Leu His Pro Asp
65 70 75 80
Phe Pro Gly Phe Gly Asn Leu Asn Pro Phe Arg Cys Arg Phe Glu Ile
85 90 95
Gln Asp Gly Ala Thr Ala Ala Leu Pro Gln Ser Lys Ile Glu Lys Ile
100 105 110
Arg Lys Glu Pro Asp His Arg Lys Ala Val Glu Met Ala Val Glu Glu
115 120 125
Ile Val Val Glu Leu Gln Thr Leu Asp Glu Ser Ser His Arg Pro Asp
130 135 140
Val Ala Ile Val Ala Leu Pro Thr Glu Leu Ile Glu Arg Val Trp Asn
145 150 155 160
Ala Lys Val Asp Ser Arg Ser Ser Thr Glu Arg Glu Asp Ser Ser Gly
165 170 175
Ser Asp Ala Pro Asn Phe Arg Gly Met Leu Lys Ala Arg Ala Met Gly
180 185 190
Leu Ser Tyr Pro Val Gln Ile Val Trp Glu Asp Val Ile Asp Glu Lys
195 200 205
Ala Ser Ile Pro Arg Lys Ile Lys Glu Ser Ser Asn Arg Asp Ile Gln
210 215 220
Asp Gln Ala Asp Arg Thr Trp Asn Leu Val Thr Thr Leu Tyr Tyr Lys
225 230 235 240
Gly Ser Gly Arg Ile Pro Trp Arg Arg Met Pro Arg Glu Asp Glu Phe
245 250 255
Ala Ala Cys Tyr Val Gly Ile Ser Phe Tyr Arg Glu Thr Gly Gly Gln
260 265 270
Gln Leu Phe Thr Ser Ala Ala Gln Met Phe Asp Glu Arg Gly Arg Gly
275 280 285
Phe Ile Leu Lys Gly Lys Arg Ala His Thr Glu Thr Arg Gly Arg His
290 295 300
Pro Tyr Met Thr Phe Asp Asp Ala Tyr Asp Leu Ala Ser Gln Val Leu
305 310 315 320
Ser Thr Tyr Lys Lys His His Lys His Phe Pro Ala Arg Val Ile Ile
325 330 335
Leu Lys Thr Ser Arg Phe Arg Asn Asp Glu Ala Glu Gly Ile Leu Lys
340 345 350
Ala Ile Asp Glu Ala Gly Thr Glu Leu Arg Asp Leu Val Trp Val Gln
355 360 365
Glu Ser Tyr Ser Val Lys Val Leu Arg Asp Gly Asn Tyr Pro Val Leu
370 375 380
Arg Gly Thr Phe Val Asn Leu Ala Gly Lys Gly Leu Leu Tyr Thr Asn
385 390 395 400
Gly Ser Met Pro Tyr Tyr Gly Thr Tyr Pro Gly Gln Tyr Asp Pro Arg
405 410 415
Pro Leu Leu Leu Cys Pro His Glu Ser Cys Asp Ser Thr Ile Ser Gln
420 425 430
Ile Ala Glu Glu Val Leu Ser Leu Thr Lys Ile Asn Trp Asn Ser Thr
435 440 445
Gln Met Asn Gln Arg Leu Pro Ile Pro Ile Arg Ala Ala Arg Lys Val
450 455 460
Gly Glu Val Leu Lys Tyr Ile Asp Glu Gly Gln Ala Val Ser Thr Asp
465 470 475 480
Tyr Arg Arg Tyr Ile
485
<210> 89
<211> 484
<212> PRT
<213> artificial sequence
<400> 89
Met Lys Phe Glu Thr Thr Ile Phe Asp Glu Pro Tyr Leu Glu Phe Gly
1 5 10 15
Asp Lys His His His Pro Asp Pro Arg Leu Gly Leu His Glu Ala Gly
20 25 30
Pro Leu Gln Thr Pro Leu Gly Asp Ala Ile Arg Ile Ala Val Val Gly
35 40 45
Asn Ser Lys Thr Val Glu Asp Thr Lys Arg Tyr Leu Asp Asp Ala Thr
50 55 60
Ala Gly Phe Pro Gly Lys Thr Glu Lys His Pro Asn Leu His Pro Asp
65 70 75 80
Phe Pro Gly Leu Gly Asn Leu Asn Pro Phe Arg Cys Lys Phe Glu Leu
85 90 95
Ala Glu Asn Ala Ala Leu Ala Ile Pro His Val Arg Ile Glu Ala Ile
100 105 110
Leu Lys Glu Pro Asn His Glu Lys Ala Val Arg Met Ala Val Asp Glu
115 120 125
Val Met Glu Gln Leu Gln Thr Ile Asp Glu Gly Thr Glu Arg Pro Asn
130 135 140
Val Ala Ile Val Ala Leu Pro Ile Asn Leu Ile Glu Arg Val Val Asn
145 150 155 160
Ala Arg Tyr Ser Pro Asp Gly Thr Thr Glu Gln Glu Asp Ser Gly Gly
165 170 175
Ser Asp Ala Pro Asn Phe Arg Gly Met Leu Lys Ala Arg Ala Met Asp
180 185 190
Leu Arg Phe Pro Ile Gln Ile Ala Trp Glu Asp Val Leu Asp Asp Ser
195 200 205
Val Ile Ile Pro Gln Lys Val Lys Glu Ala Thr Gly Arg Gln Ile Gln
210 215 220
Asp Glu Ala Asp Arg Ala Trp Asn Leu Met Thr Thr Leu Tyr Tyr Lys
225 230 235 240
Gly Thr Gly Arg Ile Pro Trp Arg Arg Met Pro Lys Glu Gly Glu Phe
245 250 255
Thr Ala Cys Tyr Ile Gly Ile Ser Phe Tyr Arg Glu Val Gly Gly Gln
260 265 270
Gln Leu Phe Thr Ser Ala Ala Gln Met Phe Asp Glu Arg Gly Arg Gly
275 280 285
Phe Ile Leu Lys Gly Lys Arg Ala Arg Thr Glu Thr Arg Gly Arg His
290 295 300
Pro Tyr Met Ala Glu Glu Asp Ala Lys Glu Leu Ile Arg Gly Ala Leu
305 310 315 320
Ala Ala Tyr Lys Ala His His Met Asn Tyr Pro Ala Arg Val Ile Val
325 330 335
Leu Lys Thr Ser Arg Phe Arg Asp Glu Glu Ala Asp Gly Ile Leu Asp
340 345 350
Ala Leu Gln Glu Val Gly Thr Glu Leu Arg Asp Leu Val Trp Val Gln
355 360 365
Glu Ser Ser His Ile Lys Val Leu Arg Asp Gly Asn Tyr Pro Val Met
370 375 380
Arg Gly Thr Phe Val Glu Met Gly Gly Lys Gly Leu Leu Tyr Thr Thr
385 390 395 400
Gly Ser Ile Pro Tyr Tyr Gly Thr Tyr Pro Gly Met Tyr Asp Pro Lys
405 410 415
Pro Leu Leu Ile Cys Pro His Ser Arg Ser Asp Ser Thr Val Lys Thr
420 425 430
Leu Ala Glu Glu Val Phe Ser Leu Thr Lys Val Asn Trp Asn Ser Thr
435 440 445
Gln Met Asn Gln Lys Leu Pro Ile Pro Ile Arg Ala Ala Arg Asn Val
450 455 460
Gly Glu Ile Leu Lys Tyr Val Thr Thr Glu Lys Val Asn Ser Asp Tyr
465 470 475 480
Gly Arg Tyr Ile
<210> 90
<211> 482
<212> PRT
<213> artificial sequence
<400> 90
Met Lys Leu His Val Leu Asp Glu Pro Pro Leu Met Phe Gly Asn Gly
1 5 10 15
Gly Arg His Ile Asp Ile Lys Ala Gly Ile Ala Thr His Gly Thr Phe
20 25 30
Asp Leu Arg Ser Gly Thr Val Pro Thr Pro Ile Gly Ile Gly Leu Val
35 40 45
Gly Thr Ser Phe Thr Val Asp Gly Val Arg Asp Trp Leu Glu Ser Cys
50 55 60
Arg Asn Gly Val Ala Ser Thr Glu Ala Asn Leu Val Glu Leu Arg Pro
65 70 75 80
Arg Phe Pro Gly Met Gln Asp Ala Leu Phe Gly Thr Gln Leu Asn Ile
85 90 95
Thr Asp Ala Ala Thr Arg Val Val Ser Arg His Glu Leu Ser Thr Ala
100 105 110
Leu Ala Gly Arg His Arg Met Arg Ala Val Gly Glu Leu Phe Leu Asp
115 120 125
His Ala Arg Asp Leu Ala Glu Arg Ser Gly Ile His Val Val Ile Val
130 135 140
Ala Pro Pro Val Glu Val Phe Thr Met Val Asp Asp Pro Glu Arg Glu
145 150 155 160
Val Asp Pro Val Leu Asp Asp Ser Glu Asp Glu Ala Pro Val Tyr Lys
165 170 175
Ser Asn Phe His Asp Ala Phe Lys Ala His Ala Leu Asp Leu Ala Ala
180 185 190
Pro Cys Gln Ile Val Arg Pro Asp Thr Tyr Gly Gly Gly Ser Thr Arg
195 200 205
Val Arg Lys Lys Gly Gly Lys Ser Asp Arg Lys Pro Ser Leu Gln Asp
210 215 220
Pro Ala Thr Arg Ala Trp Asn Phe His Thr Ala Leu Tyr Tyr Lys Ala
225 230 235 240
Gly Gly Val Pro Trp Arg Leu Val Arg Arg Ala Ala Ala Leu Asp Thr
245 250 255
Cys Tyr Val Gly Thr Ser Phe Tyr Lys Ser Leu Asp Gly Glu Arg Leu
260 265 270
Leu Thr Ser Ile Ala Gln Val Phe Asn Glu Arg Gly Glu Gly Leu Ile
275 280 285
Val Gln Gly Gly Asn Ala Arg Ile Asp Arg Arg Asp Arg Thr Ala His
290 295 300
Leu Ser Ala Asp Asp Ala Gln Thr Leu Leu Ala Arg Gly Leu Asn Ser
305 310 315 320
Tyr Arg Arg Glu His Arg Asn Met Pro Ala Arg Val Val Val His Lys
325 330 335
Thr Ser Tyr Phe Asp Ala Ala Glu Ile Glu Gly Phe Arg Gln Ala Ala
340 345 350
Arg Asp Glu Arg Val Glu Leu Leu Asp Leu Val Ser Val Arg Arg Ala
355 360 365
Gly Ala Arg Leu Phe Arg Ala Ala Glu His Ala Val Gln Arg Gly Thr
370 375 380
Thr Leu Gln Thr Asp Gly Arg Ser Gly Leu Ile Tyr Leu Lys Gly Thr
385 390 395 400
Val Pro Tyr Phe Arg Thr Tyr Pro Gly Met Tyr Val Pro Arg Ala Leu
405 410 415
Glu Tyr Thr Arg Asp Asp Gly Thr Thr Ser Pro Leu Glu Leu Ala Lys
420 425 430
Glu Leu Leu Glu Leu Ser Lys Leu Asn Phe Asn Asn Thr Gln Phe Asp
435 440 445
Ser Gly Asp Pro Ile Thr Val Arg Ala Ala Arg Arg Val Gly Asp Ile
450 455 460
Leu Lys His Val Gly Ala Asp Lys Ser Val Gln Ser Arg Phe Arg Tyr
465 470 475 480
Phe Thr
<210> 91
<211> 485
<212> PRT
<213> artificial sequence
<400> 91
Met Lys Ile Leu Arg Phe Asp Glu Pro Glu Leu Gln Phe Gly Thr Ser
1 5 10 15
Thr His Val Asp Ile Arg Phe Gly Leu Met Asn Tyr Ser Pro Leu Asp
20 25 30
Phe Asp Ser Asp Ala Ala Pro Lys Arg Ile Arg Val Gly Ile Val Gly
35 40 45
Ser Ala Ala Ser Ile Glu Gly Leu Arg Asp Trp Leu Glu Arg Cys Arg
50 55 60
Asn Glu Ile Pro Ala Lys Gln Ser Arg Gln Pro Asn Leu Phe Pro Arg
65 70 75 80
Phe Pro Gly Phe Arg Ser Asp Ile Ala Phe Cys Ser Glu Leu Thr Phe
85 90 95
Asp Ser Ala Leu Glu Arg Pro Ile Ser Ser Ala Ala Ile Gly Asp Ile
100 105 110
Ile Thr Gly Thr Val Arg Asp Glu Gln Lys Val Arg Ala Val Thr Ala
115 120 125
Ile Val Gly Glu Val Arg Ser Leu Leu Glu Lys Lys Pro Asp Val Ile
130 135 140
Val Cys Ala Leu Pro Pro Gln Leu Leu Asp Ala Phe Glu Pro Asp Asp
145 150 155 160
Asp Ser Val Asp Leu Asn Asn Glu Glu Ser Gly Pro Ser Thr Pro Asp
165 170 175
Thr Asp Thr Ile Asp Phe His His Leu Leu Lys Ala Arg Cys Met Ala
180 185 190
Leu Pro Arg Ala Cys Pro Leu Gln Leu Val Leu Pro Gly Thr Tyr Asp
195 200 205
Ser Lys Ser Arg Arg Arg Gly Lys Lys Arg Gly Arg Asp Ile Arg Pro
210 215 220
Leu Gln Asp Asp Ala Thr Arg Ala Trp Asn Phe His Thr Ala Leu Tyr
225 230 235 240
Tyr Lys Ala Asn Gly Val Pro Trp Arg Leu Val His Asp Pro Ser Lys
245 250 255
Leu Gln Thr Cys Phe Val Gly Val Gly Phe Tyr Arg Thr Leu Asp Arg
260 265 270
Glu Ser Leu Phe Ala Ser Val Ala Gln Val Phe Asn Glu Arg Gly Asn
275 280 285
Gly Val Val Val Arg Gly Glu Ala Ala Val Val Glu Lys Glu Asp Arg
290 295 300
Gln Val His Leu Ser Ala Asp Asn Ala Tyr Ile Leu Leu Cys Arg Ala
305 310 315 320
Leu Asp Glu Tyr Arg Ser Glu His Lys Thr Ile Pro Ala Arg Ile Val
325 330 335
Val His Lys Thr Ser Ser His Asn Ala Ala Glu Ile Asp Gly Phe Thr
340 345 350
Arg Ala Ala Lys Glu His Arg Val Glu Tyr Cys Glu Leu Leu Ser Leu
355 360 365
Gly Lys Ser Phe Ile Arg Leu Phe Arg Asn Ala Glu Tyr Pro Pro Leu
370 375 380
Arg Gly Thr Phe Leu Ser Leu Asp Asp Arg Asn His Leu Leu Tyr Thr
385 390 395 400
Arg Gly Ser Val Glu Phe Tyr Ala Thr Tyr Pro Gly Met Tyr Met Pro
405 410 415
Arg Ser Ile Leu Ile Gly Cys Asp Arg Val Glu Gln Thr Pro Arg Phe
420 425 430
Leu Ala Glu Glu Ile Leu Thr Leu Thr Lys Met Asn Trp Asn Asp Thr
435 440 445
Gln Phe Asp Gly Gly Met Pro Ile Thr Ile Arg Ala Ala Arg Gln Val
450 455 460
Gly Asn Ile Leu Lys Tyr Ser Gly Gln Asn Asp Pro Val Pro Ser Gln
465 470 475 480
Tyr Ser Phe Tyr Met
485
<210> 92
<211> 685
<212> PRT
<213> artificial sequence
<400> 92
Met Asn His Leu Gly Lys Thr Glu Val Phe Leu Asn Arg Phe Ala Leu
1 5 10 15
Arg Pro Leu Asn Pro Glu Glu Leu Arg Pro Trp Arg Leu Glu Val Val
20 25 30
Leu Asp Pro Pro Pro Gly Arg Glu Glu Val Tyr Pro Leu Leu Ala Gln
35 40 45
Val Ala Arg Arg Ala Gly Gly Val Thr Val Arg Met Gly Asp Gly Leu
50 55 60
Ala Ser Trp Ser Pro Pro Glu Val Leu Val Leu Glu Gly Thr Leu Ala
65 70 75 80
Arg Met Gly Gln Thr Tyr Ala Tyr Arg Leu Tyr Pro Lys Gly Arg Arg
85 90 95
Pro Leu Asp Pro Lys Asp Pro Gly Glu Arg Ser Val Leu Ser Ala Leu
100 105 110
Ala Arg Arg Leu Leu Gln Glu Arg Leu Arg Arg Leu Glu Gly Val Trp
115 120 125
Val Glu Gly Leu Ala Val Tyr Arg Arg Glu His Ala Arg Gly Pro Gly
130 135 140
Trp Arg Val Leu Gly Gly Ala Val Leu Asp Leu Trp Val Ser Asp Ser
145 150 155 160
Gly Ala Phe Leu Leu Glu Val Asp Pro Ala Tyr Arg Ile Leu Cys Glu
165 170 175
Met Ser Leu Glu Ala Trp Leu Ala Gln Gly His Pro Leu Pro Lys Arg
180 185 190
Val Arg Asn Ala Tyr Asp Arg Arg Thr Trp Glu Leu Leu Arg Leu Gly
195 200 205
Glu Glu Asp Pro Lys Glu Leu Pro Leu Pro Gly Gly Leu Ser Leu Leu
210 215 220
Asp Tyr His Ala Ser Lys Gly Arg Leu Gln Gly Arg Glu Gly Gly Arg
225 230 235 240
Val Ala Trp Val Ala Asp Pro Lys Asp Pro Arg Lys Pro Ile Pro His
245 250 255
Leu Thr Gly Leu Leu Val Pro Val Leu Thr Leu Glu Asp Leu His Glu
260 265 270
Glu Glu Gly Ser Leu Ala Leu Ser Leu Pro Trp Glu Glu Arg Arg Arg
275 280 285
Arg Thr Arg Glu Ile Ala Ser Trp Ile Gly Arg Arg Leu Gly Leu Gly
290 295 300
Thr Pro Glu Ala Val Arg Ala Gln Ala Tyr Arg Leu Ser Ile Pro Lys
305 310 315 320
Leu Met Gly Arg Arg Ala Val Ser Lys Pro Ala Asp Ala Leu Arg Val
325 330 335
Gly Phe Tyr Arg Ala Gln Glu Thr Ala Leu Ala Leu Leu Arg Leu Asp
340 345 350
Gly Ala Gln Gly Trp Pro Glu Phe Leu Arg Arg Ala Leu Leu Arg Ala
355 360 365
Phe Gly Ala Ser Gly Ala Ser Leu Arg Leu His Thr Leu His Ala His
370 375 380
Pro Ser Gln Gly Leu Ala Phe Arg Glu Ala Leu Arg Lys Ala Lys Glu
385 390 395 400
Glu Gly Val Gln Ala Val Leu Val Leu Thr Pro Pro Met Ala Trp Glu
405 410 415
Asp Arg Asn Arg Leu Lys Ala Leu Leu Leu Arg Glu Gly Leu Pro Ser
420 425 430
Gln Ile Leu Asn Val Pro Leu Arg Glu Glu Glu Arg His Arg Trp Glu
435 440 445
Asn Ala Leu Leu Gly Leu Leu Ala Lys Ala Gly Leu Gln Val Val Ala
450 455 460
Leu Ser Gly Ala Tyr Pro Ala Glu Leu Ala Val Gly Phe Asp Ala Gly
465 470 475 480
Gly Arg Glu Ser Phe Arg Phe Gly Gly Ala Ala Cys Ala Val Gly Gly
485 490 495
Asp Gly Gly His Leu Leu Trp Thr Leu Pro Glu Ala Gln Ala Gly Glu
500 505 510
Arg Ile Pro Gln Glu Val Val Trp Asp Leu Leu Glu Glu Thr Leu Trp
515 520 525
Ala Phe Arg Arg Lys Ala Gly Arg Leu Pro Ser Arg Val Leu Leu Leu
530 535 540
Arg Asp Gly Arg Val Pro Gln Asp Glu Phe Ala Leu Ala Leu Glu Ala
545 550 555 560
Leu Ala Arg Glu Gly Ile Ala Tyr Asp Leu Val Ser Val Arg Lys Ser
565 570 575
Gly Gly Gly Arg Val Tyr Pro Val Gln Gly Arg Leu Ala Asp Gly Leu
580 585 590
Tyr Val Pro Leu Glu Asp Lys Thr Phe Leu Leu Leu Thr Val His Arg
595 600 605
Asp Phe Arg Gly Thr Pro Arg Pro Leu Lys Leu Val His Glu Ala Gly
610 615 620
Asp Thr Pro Leu Glu Ala Leu Ala His Gln Ile Phe His Leu Thr Arg
625 630 635 640
Leu Tyr Pro Ala Ser Gly Phe Ala Phe Pro Arg Leu Pro Ala Pro Leu
645 650 655
His Leu Ala Asp Arg Leu Val Lys Glu Val Gly Arg Leu Gly Ile Arg
660 665 670
His Leu Lys Glu Val Asp Arg Glu Lys Leu Phe Phe Val
675 680 685
<210> 93
<211> 776
<212> PRT
<213> artificial sequence
<400> 93
Ala Pro Val Gln Ala Ala Asp Glu Met Tyr Asp Ser Asn Pro His Pro
1 5 10 15
Asp Arg Arg Gln Leu Val Ser Asn Gly Phe Glu Val Asn Leu Pro Asp
20 25 30
Gln Val Glu Val Ile Val Arg Asp Leu Pro Asp Pro Ser Lys Val Lys
35 40 45
Glu Glu Arg Thr Arg Leu Met Gly Tyr Trp Phe Val His Trp Phe Asp
50 55 60
Gly Lys Leu Phe His Leu Arg Ile Lys Ala Gly Gly Pro Asn Val Asp
65 70 75 80
Gly Glu His Arg Ala Ile Arg Thr Ala Glu His Pro Trp Leu Leu Arg
85 90 95
Ala Arg Leu Asp Asp Ala Leu Glu Glu Ala Leu Pro Lys Tyr Ala Ala
100 105 110
Val Lys Lys Arg Pro Phe Thr Phe Leu Ala Gln Lys Asp Glu Leu Ile
115 120 125
Asp Ala Ala Ala Thr Ala Ala Gly Leu Ser His Arg Leu Leu Asn Ser
130 135 140
Phe Lys Val Ile Pro Arg Phe Ala Leu Ser Pro Lys Ile Tyr Glu Pro
145 150 155 160
Val Asp Gly Thr Thr Arg Val Gly Val Phe Val Thr Ile Gly Met Arg
165 170 175
Tyr Asp Ile Glu Ala Ser Leu Arg Asp Leu Leu Glu Ala Gly Ile Asp
180 185 190
Leu Arg Gly Met Tyr Val Val Arg Arg Lys Arg Gln Pro Gly Glu Arg
195 200 205
Gly Leu Leu Gly Arg Val Arg Ala Ile Ser Asp Asp Met Val Gln Leu
210 215 220
Phe Glu Glu Thr Asp Leu Ala Ser Val Asn Val Asn Asp Ala Lys Leu
225 230 235 240
Glu Gly Ser Lys Glu Asn Phe Thr Arg Cys Leu Ser Ala Leu Leu Gly
245 250 255
His Asn Tyr Lys Lys Leu Leu Asn Ala Leu Asp Asp Gln Glu Ala Gly
260 265 270
Tyr Arg Thr Gly Pro Arg Phe Asp Asp Ala Val Arg Arg Met Gly Glu
275 280 285
Phe Leu Ala Lys Lys Pro Ile Arg Leu Ala Asp Asn Ile Asn Ala Gln
290 295 300
Val Gly Asp Arg Ile Val Phe Ser Asn Glu Gly Gln Ala Arg Asn Val
305 310 315 320
Arg Leu Ala Pro Lys Val Glu Tyr Val Phe Asp Arg Thr Gly Ala Lys
325 330 335
Ser Ala Glu Tyr Ala Trp Arg Gly Leu Ser Gln Phe Gly Pro Phe Asp
340 345 350
Arg Pro Ser Phe Ala Asn Arg Ser Pro Arg Ile Leu Val Val Tyr Pro
355 360 365
Ser Ser Thr Gln Gly Lys Val Glu Asn Phe Leu Ser Ala Phe Arg Asp
370 375 380
Gly Met Gly Ser Asn Tyr Ser Gly Phe Ser Lys Gly Phe Val Asp Leu
385 390 395 400
Met Gly Leu Thr Lys Val Glu Phe Val Met Cys Pro Val Glu Val Ser
405 410 415
Ser Ala Asp Arg Asn Gly Ala His Thr Lys Tyr Asn Ser Ala Ile Glu
420 425 430
Asp Lys Leu Ala Gly Ala Gly Glu Val His Ala Gly Ile Val Val Leu
435 440 445
Phe Glu Asp His Ala Arg Leu Pro Asp Asp Arg Asn Pro Tyr Ile His
450 455 460
Thr Lys Ser Leu Leu Leu Thr Leu Gly Val Pro Thr Gln Gln Val Arg
465 470 475 480
Met Pro Thr Val Leu Leu Glu Pro Lys Ser Leu Gln Tyr Thr Leu Gln
485 490 495
Asn Phe Ser Ile Ala Thr Tyr Ala Lys Leu Asn Gly Thr Pro Trp Thr
500 505 510
Val Asn His Asp Lys Ala Ile Asn Asp Glu Leu Val Val Gly Met Gly
515 520 525
Leu Ala Glu Leu Ser Gly Ser Arg Thr Glu Lys Arg Gln Arg Phe Val
530 535 540
Gly Ile Thr Thr Val Phe Ala Gly Asp Gly Ser Tyr Leu Leu Gly Asn
545 550 555 560
Val Ser Lys Glu Cys Glu Tyr Glu Gly Tyr Ser Asp Ala Ile Arg Glu
565 570 575
Ser Met Thr Gly Ile Leu Arg Glu Leu Lys Lys Arg Asn Asn Trp Arg
580 585 590
Pro Gly Asp Thr Val Arg Val Val Phe His Ala His Arg Pro Leu Lys
595 600 605
Arg Val Asp Val Ala Ser Ile Val Phe Glu Cys Thr Arg Glu Ile Gly
610 615 620
Ser Asp Gln Asn Ile Gln Met Ala Phe Val Thr Val Ser His Asp His
625 630 635 640
Pro Phe Val Leu Ile Asp Arg Ser Glu Arg Gly Leu Glu Ala Tyr Lys
645 650 655
Gly Ser Thr Ala Arg Lys Gly Val Phe Ala Pro Pro Arg Gly Ala Ile
660 665 670
Ser Arg Val Gly Arg Leu Thr Arg Leu Leu Ala Val Asn Ser Pro Gln
675 680 685
Leu Ile Lys Arg Ala Asn Thr Pro Leu Pro Thr Pro Leu Leu Val Ser
690 695 700
Leu His Pro Asp Ser Thr Phe Lys Asp Val Asp Tyr Leu Ala Glu Gln
705 710 715 720
Ala Leu Lys Phe Thr Ser Leu Ser Trp Arg Ser Thr Leu Pro Ala Ala
725 730 735
Thr Pro Val Thr Ile Phe Tyr Ser Glu Arg Ile Ala Glu Leu Leu Gly
740 745 750
Arg Leu Lys Ser Ile Pro Asn Trp Ser Ser Ala Asn Leu Asn Ile Lys
755 760 765
Leu Lys Trp Ser Arg Trp Phe Leu
770 775
<210> 94
<211> 50
<212> DNA
<213> artificial sequence
<400> 94
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 95
<211> 50
<212> DNA
<213> artificial sequence
<400> 95
ggcttctccc gcaaaagtat tacagggtca taatgttttt ggtacaaccg 50
<210> 96
<211> 27
<212> DNA
<213> artificial sequence
<400> 96
cgcgagctga aaaggtggca tcaattc 27
<210> 97
<211> 50
<212> DNA
<213> artificial sequence
<400> 97
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 98
<211> 50
<212> DNA
<213> artificial sequence
<400> 98
ggcttctccc gcaaaagtat tacagggtca taatgttttt ggtacaaccg 50
<210> 99
<211> 40
<212> DNA
<213> artificial sequence
<400> 99
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt 40
<210> 100
<211> 30
<212> DNA
<213> artificial sequence
<400> 100
ggcttctccc gcaaaagtat tacagggtca 30
<210> 101
<211> 50
<212> DNA
<213> artificial sequence
<400> 101
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 102
<211> 50
<212> DNA
<213> artificial sequence
<400> 102
ggcttctccc gcaaaagtat tacagggtca taatgttttt ggtacaaccg 50
<210> 103
<211> 27
<212> DNA
<213> artificial sequence
<400> 103
cgcgagctga aaaggtggca tcaattc 27
<210> 104
<211> 27
<212> DNA
<213> artificial sequence
<400> 104
ttaaatatgc aactaaagta cggtgtc 27
<210> 105
<211> 30
<212> DNA
<213> artificial sequence
<400> 105
ttaaatatgc aactaaagta cggtgtctgg 30
<210> 106
<211> 40
<212> DNA
<213> artificial sequence
<400> 106
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt 40
<210> 107
<211> 50
<212> DNA
<213> artificial sequence
<400> 107
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 108
<211> 27
<212> DNA
<213> artificial sequence
<400> 108
ggcttctccc gcaaaagtat tacaggg 27
<210> 109
<211> 30
<212> DNA
<213> artificial sequence
<400> 109
ggcttctccc gcaaaagtat tacagggtca 30
<210> 110
<211> 40
<212> DNA
<213> artificial sequence
<400> 110
ggcttctccc gcaaaagtat tacagggtca taatgttttt 40
<210> 111
<211> 50
<212> DNA
<213> artificial sequence
<400> 111
ggcttctccc gcaaaagtat tacagggtca taatgttttt ggtacaaccg 50
<210> 112
<211> 27
<212> DNA
<213> artificial sequence
<400> 112
cgcgagctga aaaggtggca tcaattc 27
<210> 113
<211> 50
<212> DNA
<213> artificial sequence
<400> 113
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 114
<211> 50
<212> DNA
<213> artificial sequence
<400> 114
ggcttctccc gcaaaagtat tacagggtca taatgttttt ggtacaaccg 50
<210> 115
<212> DNA
<213> artificial sequence
<400> 115
cgcgagctga aaaggtggca tcaattc 27
<210> 116
<211> 50
<212> DNA
<213> artificial sequence
<400> 116
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 117
<211> 50
<212> DNA
<213> artificial sequence
<400> 117
ggcttctccc gcaaaagtat tacagggtca taatgttttt ggtacaaccg 50
<210> 118
<211> 50
<212> DNA
<213> artificial sequence
<400> 118
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 119
<211> 50
<212> DNA
<213> artificial sequence
<400> 119
tattaacgtt tacaatttaa atatttgctt atacaatctt cctgtttttg 50
<210> 120
<211> 50
<212> DNA
<213> artificial sequence
<400> 120
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 121
<211> 50
<212> DNA
<213> artificial sequence
<400> 121
taaaaatttt tatccttgcg ttgaaataaa ggcttctccc gcaaaagtat 50
<210> 122
<211> 50
<212> DNA
<213> artificial sequence
<400> 122
tattaacgtt tacaatttaa atatttgctt atacaatctt cctgtttttg 50
<210> 123
<211> 50
<212> DNA
<213> artificial sequence
<400> 123
ttttacaacg tcgtgactgg gaaaaccctg gcgttaccca acttaatcgc 50
<210> 124
<211> 50
<212> DNA
<213> artificial sequence
<400> 124
tgattataaa aacacttctc aggattctgg cgtaccgttc ctgtctaaaa 50
<210> 125
<211> 50
<212> DNA
<213> artificial sequence
<400> 125
tttatttctg ttttacgtgc aaataatttt gatatggtag gttctaaccc 50
<210> 126
<211> 50
<212> DNA
<213> artificial sequence
<400> 126
gttattctct ctgtaaaggc tgctattttc atttttgacg ttaaacaaaa 50
<210> 127
<211> 50
<212> DNA
<213> artificial sequence
<400> 127
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 128
<211> 50
<212> DNA
<213> artificial sequence
<400> 128
taaaaatttt tatccttgcg ttgaaataaa ggcttctccc gcaaaagtat 50
<210> 129
<211> 50
<212> DNA
<213> artificial sequence
<400> 129
tattaacgtt tacaatttaa atatttgctt atacaatctt cctgtttttg 50
<210> 130
<211> 50
<212> DNA
<213> artificial sequence
<400> 130
ttttacaacg tcgtgactgg gaaaaccctg gcgttaccca acttaatcgc 50
<210> 131
<211> 18
<212> DNA
<213> artificial sequence
<400> 131
ttaaatatgc aactaaag 18
<210> 132
<211> 21
<212> DNA
<213> artificial sequence
<400> 132
tactttagtt gcatatttaa a 21
<210> 133
<211> 27
<212> DNA
<213> artificial sequence
<400> 133
ttaaatatgc aactaaagta cggtgtc 27
<210> 134
<211> 30
<212> DNA
<213> artificial sequence
<400> 134
ttaaatatgc aactaaagta cggtgtctgg 30
<210> 135
<211> 40
<212> DNA
<213> artificial sequence
<400> 135
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt 40
<210> 136
<211> 50
<212> DNA
<213> artificial sequence
<400> 136
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 137
<211> 18
<212> DNA
<213> artificial sequence
<400> 137
tattaacgtt tacaattt 18
<210> 138
<211> 21
<212> DNA
<213> artificial sequence
<400> 138
tattaacgtt tacaatttaa a 21
<210> 139
<211> 27
<212> DNA
<213> artificial sequence
<400> 139
tattaacgtt tacaatttaa atatttg 27
<210> 140
<211> 30
<212> DNA
<213> artificial sequence
<400> 140
tattaacgtt tacaatttaa atatttgctt 30
<210> 141
<211> 40
<212> DNA
<213> artificial sequence
<400> 141
tattaacgtt tacaatttaa atatttgctt atacaatctt 40
<210> 142
<211> 50
<212> DNA
<213> artificial sequence
<400> 142
tattaacgtt tacaatttaa atatttgctt atacaatctt cctgtttttg 50
<210> 143
<211> 50
<212> DNA
<213> artificial sequence
<400> 143
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 144
<211> 50
<212> DNA
<213> artificial sequence
<400> 144
tattaacgtt tacaatttaa atatttgctt atacaatctt cctgtttttg 50
<210> 145
<211> 50
<212> DNA
<213> artificial sequence
<400> 145
ttgtataagc aaatatttaa attgtaaacg ttaatatttt gttaaaattc 50
<210> 146
<211> 27
<212> DNA
<213> artificial sequence
<400> 146
ttaaatatgc aactaaagta cggtgtc 27
<210> 147
<211> 30
<212> DNA
<213> artificial sequence
<400> 147
ttaaatatgc aactaaagta cggtgtctgg 30
<210> 148
<211> 40
<212> DNA
<213> artificial sequence
<400> 148
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt 40
<210> 149
<211> 50
<212> DNA
<213> artificial sequence
<400> 149
ttaaatatgc aactaaagta cggtgtctgg aagtttcatt ccatataaca 50
<210> 150
<211> 50
<212> DNA
<213> artificial sequence
<400> 150
ttgtataagc aaatatttaa attgtaaacg ttaatatttt gttaaaattc 50
<210> 151
<211> 50
<212> DNA
<213> artificial sequence
<400> 151
ttgtataagc aaatatttaa attgtaaacg ttaatatttt gttaaaattc 50
<210> 152
<211> 30
<212> DNA
<213> artificial sequence
<400> 152
ccgctacagg gcgcgtacta tggttgcttt 30
<210> 153
<211> 50
<212> DNA
<213> artificial sequence
<400> 153
ttgcaatggc tggcggtaat attgttctgg atattaccag caaggccgat 50
<210> 154
<211> 50
<212> DNA
<213> artificial sequence
<400> 154
ccgctacagg gcgcgtacta tggttgcttt gacgagcacg tataacgtgc 50
<210> 155
<211> 48
<212> DNA
<213> artificial sequence
<400> 155
tatataatac gactcactat aggtggcgat gttttagggc tatcagtt 48
<210> 156
<211> 23
<212> DNA
<213> artificial sequence
<400> 156
ggcgctggca agtgtagcgg tca 23
<210> 157
<211> 27
<212> DNA
<213> artificial sequence
<400> 157
tcagagcggg agctaaacag gaggccg 27

Claims (44)

1. A method of nucleic acid polymerase reaction based on Ago proteins and/or PIWI domain-containing proteins, characterized in that the method comprises the steps of: DNA or RNA is taken as a template, ago protein and/or protein containing a PIWI structural domain promotes primer specific targeting binding with a template complementary to the sequence of the Ago protein or the protein, so that polymerization activity of polymerase or reverse transcriptase is initiated, dNTP is taken as a raw material, and complementary strand of the template is synthesized according to a base complementary pairing principle and a semi-reserved replication principle.
2. The method of claim 1, wherein the Ago protein and/or the PIWI domain-containing protein and the nucleic acid polymerase are present in the same reaction system for nucleic acid polymerase chain reaction to effect nucleic acid amplification.
3. The method of claim 1, wherein the Ago proteins comprise eukaryotic Ago proteins and prokaryotic Ago proteins.
4. The method of claim 1, wherein the Ago protein is an Ago protein that promotes or enhances primer and template binding;
and/or, the Ago protein can be rapidly and specifically targeted to a binding template under the guidance of a primer;
and/or, the Ago protein can form a binary complex specific targeting binding template with the primer.
5. The method of claim 1, wherein said Ago protein comprises a protein that is annotated to contain a PIWI-like domain by database protein sequence alignment; the PIWI-like domain is used to bind nucleic acids.
6. The method of claim 1, wherein the Ago protein is a protein that is active under conditions of a polymerase or reverse transcriptase active buffer within a temperature range where the polymerase or reverse transcriptase is active.
7. The method of claim 1, wherein the binary complex formed by the Ago protein and the primer can trigger the polymerization activity of a polymerase or a reverse transcriptase.
8. The method of claim 1, wherein the Ago protein is a protein capable of binding primers greater than 24nt in length.
9. The method of claim 1, wherein the Ago protein is one or more selected from the sequences set forth in SEQ ID nos. 1-93; and/or one or more amino acid sequences selected from the group consisting of amino acid sequences having at least 50% sequence homology to the sequences shown in SEQ ID NOS.1 to 93.
10. The method of claim 9, wherein the Ago protein is one or more of NgAgo, maAgo, hpAgo, naAgo, ntAgo, npAgo, hbAgo, tbAgo, teAgo, hlAgo, miAgo, syAgo, cpAgo, ibAgo, fpAgo, haAgo, mfAgo, plAgo, tcAgo, aaAgo, ssAgo, toAgo, mkAgo, seAgo, scAgo, afAgo, exAgo, lyAgo, sjAgo, cbAgo, hkAgo, baAgo, bgAgo, hmAgo, mlAgo, phAgo, rbAgo, mpAgo, kmAgo, blAgo, capAgo, calAgo, cbtAgo, cdAgo, ciAgo, csAgo, csdAgo, clcAgo, cloAgo, dlAgo, euAgo, prAgo, pxAgo, bwAgo, bcAgo, cbjAgo, gtAgo, keAgo, kpAgo, lsAgo, lbAgo, marAgo, poAgo, paAgo, phpAgo, roAgo, tmAgo, thAgo, tvAgo, tbcAgo, tdAgo, bfAgo, beAgo, brAgo, coAgo, deAgo, pmAgo, pbAgo, rsAgo, mbpAgo, halaAgo, halAgo, hrAgo, hvAgo, abAgo, amAgo, atAgo, abbAgo, adAgo, dbAgo, ppAgo, ttAgo, rsAgo.
11. The method of claim 10, wherein the Ago protein is one or more of MlAgo, calAgo, dmCalAgo, afAgo, hlAgo, marAgo, poAgo, roAgo, gtAgo, beAgo, brAgo, coAgo, tbcAgo, ssAgo, dlAgo, kpAgo, tcAgo, thAgo, bwAgo.
12. The method of claim 11, wherein the Ago protein is MlAgo, calAgo, dmCalAgo.
13. The method of claim 1, wherein the PIWI domain-containing protein is a protein that promotes or enhances complementary binding of the primer to the template;
and/or, the PIWI domain-containing protein is rapidly and specifically targeted to the binding template under the guidance of a primer;
and/or, the PIWI domain-containing protein and the primer form a binary complex specific targeting binding template.
14. The method of claim 1, wherein the PIWI domain-containing protein is identified by a database protein sequence alignment; the PIWI-like domain is used to bind nucleic acids.
15. The method of claim 1, wherein the PIWI domain-containing protein is a protein capable of being active under conditions of a polymerase or reverse transcriptase active buffer within a temperature range where the polymerase or reverse transcriptase is active.
16. The method of claim 1, wherein the binary complex of the PIWI domain-containing protein and the primer initiates the polymerization activity of a polymerase or reverse transcriptase.
17. The method of claim 1, wherein the PIWI domain-containing protein is a protein capable of binding primers greater than 24nt in length.
18. The method of claim 1, wherein the polymerase is a polymerase that is active under temperature conditions that simultaneously maintain the Ago protein and/or PIWI domain-containing protein active.
19. The method of claim 18, wherein the polymerase is selected from the group consisting of DNA polymerases that are resistant to high temperatures of 95 ℃ without inactivation, and/or DNA polymerases that are resistant to >80 ℃.
20. The method of claim 19, wherein the polymerase is One or more of Taq, phanta, one Taq, la Taq, SD-Taq, vent, bst DNA polymerase, bst 2.0DNA polymerase, bst 3.0DNA polymerase, bst DNA polymerase, phi29 DNA polymerase.
21. The method of claim 1, wherein the primer acts as a primer that targets binding to the template in a nucleic acid polymerase reaction and simultaneously acts as a guide for the Ago protein and/or PIWI domain-containing protein.
22. The method of claim 1, wherein the primer is a primer that reacts the Ago protein and/or PIWI domain-containing protein with the polymerase with optimal activity.
23. The method of claim 1, wherein the length of the primer ranges under conditions that keep the polymerase active; and/or the GC content of the primer is in a range provided that the polymerase is maintained active.
24. The method of claim 21, wherein the primer length is 24nt to 80nt; and/or, the GC content of the primer is 10% -50%.
25. The method of claim 1, wherein said Ago protein and/or PIWI domain-containing protein acts as an annealing promoting enzyme in said nucleic acid polymerase chain reaction.
26. The method of claim 1, wherein the reverse transcriptase is selected from one or more of bst3.0 DNAPolymerase, thermostable RTase, AMV RTase, M-MLVRtase.
27. The method of claim 1, wherein the method is performed at a temperature that maintains the activity of both the Ago protein and/or PIWI domain-containing protein and the polymerase.
28. The method of claim 27, wherein the reaction is performed at a constant temperature or at a variable temperature.
29. The method of claim 28, wherein,
the variable temperature comprises a first temperature and a second temperature;
wherein the first temperature is a temperature capable of sufficiently opening a double-stranded template while not affecting the Ago protein and/or PIWI domain-containing protein activity, polymerase activity; opening a DNA double strand at the first temperature and maintaining the activity of the Ago protein and/or the PIWI domain-containing protein and the activity of the polymerase, and rapidly and specifically targeting a binding template by the Ago protein and/or the PIWI domain-containing protein and a primer;
wherein the second temperature is a temperature at which polymerase activity is maintained; and under the action of DNA polymerase, performing nucleic acid polymerase chain reaction by taking dNTPs as reaction raw materials at the second temperature.
30. The method of claim 29, wherein the first temperature is 80 ℃ to 100 ℃; and/or, the second temperature is 30-75 ℃.
31. The method of claim 28, wherein the double-stranded DNA is opened by the action of a helicase at the constant temperature, and the Ago protein and/or PIWI domain-containing protein and the primer are targeted to bind rapidly and specifically to the complementary sequence of the template, while the nucleic acid polymerase chain reaction is performed by the action of a DNA polymerase using the single-stranded DNA as the template.
32. The method of claim 31, wherein the constant temperature is from 30 ℃ to 70 ℃.
33. The method of claim 31, wherein the helicase is a helicase capable of opening double stranded template DNA at a constant temperature while maintaining Ago protein and/or PIWI domain-containing protein, and polymerase activity.
34. The method of claim 33, wherein the helicase is one or more of Ec Uvrd helicase, tte Uvrd helicase, T7gp4B helicase.
35. The method of claim 1, further wherein the method is an Ago and/or PIWI domain-containing protein-RT-PCR nucleic acid amplification method: taking RNA as a template, rapidly and specifically targeting and combining the Ago protein and/or the protein containing the PIWI structural domain with a primer to form template RNA, and synthesizing first-strand cDNA under the action of reverse transcriptase; and taking the first strand cDNA as a template, and rapidly and specifically combining the Ago protein and/or the PIWI structural domain-containing protein with a primer in a targeting manner with the cDNA template, and simultaneously carrying out nucleic acid polymerase chain reaction under the action of DNA polymerase.
36. The method of claim 1, further wherein the method is a one-tube multi-site nucleic acid amplification method based on Ago and/or PIWI domain-containing protein-RCR: DNA or RNA is used as a template, the Ago protein and/or the protein containing the PIWI structural domain and a primer are quickly and specifically combined with the complementary sequence of the template in a targeted manner, and then under the action of polymerase or reverse transcriptase, dNTP is used as a reaction raw material to carry out nucleic acid polymerase chain reaction.
37. A nucleic acid polymerase reaction system based on Ago proteins and/or PIWI domain-containing proteins, characterized in that the system comprises: ago proteins and/or PIWI domain-containing proteins, and polymerases; wherein the polymerase and the Ago protein and/or the PIWI domain-containing protein coexist in the reaction system, and the nucleic acid polymerase reaction is carried out under the enzymatic reaction of the polymerase.
38. The nucleic acid polymerase reaction system of claim 37, characterized in that the Ago protein and/or the PIWI domain-containing protein is active and the polymerase is active in the reaction system.
39. The nucleic acid polymerase reaction system of claim 37, characterized in that the system comprises primers; the primer is simultaneously and specifically targeted to a template with the Ago protein and/or the PIWI domain-containing protein and serves as a primer in a PCR reaction.
40. The nucleic acid polymerase reaction system of claim 39, characterized in that the primers allow the Ago protein and/or the PIWI domain-containing protein to react with the polymerase with optimal activity.
41. An Ago protein and/or a PIWI domain containing protein-primer binary complex, characterized in that it comprises an Ago protein and/or a PIWI domain containing protein or a nucleic acid encoding an Ago protein and/or a PIWI domain containing protein, and a primer.
42. The binary complex of claim 41, wherein the complex is capable of rapid specific targeting of a template nucleic acid comprising a sequence complementary to the primer, and is capable of initiating the polymerization activity of a polymerase or reverse transcriptase.
43. A composition/kit comprising an Ago protein and/or a PIWI domain-containing protein, a nucleic acid polymerase reaction system based on an Ago protein and/or a PIWI domain-containing protein according to claim 37, and/or an Ago protein and/or a PIWI domain-containing protein-primer binary complex according to claim 41.
44. An application, characterized in that it is: use of Ago proteins and/or PIWI domain containing proteins, a nucleic acid polymerase reaction system based on PIWI domain containing proteins according to claim 37, ago proteins and/or PIWI domain containing protein-primer binary complexes according to claim 41, and/or a composition/reagent/kit according to claim 43 in a nucleic acid polymerase reaction.
CN202210042552.3A 2022-01-14 2022-01-14 Ago protein/PIWI domain-containing protein-based nucleic acid polymerase reaction method and application Pending CN116479095A (en)

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