METHODS AND COMPOSITIONS FOR CONTROLLING ROTIFERS

Information

  • Patent Application
  • 20140296137
  • Publication Number
    20140296137
  • Date Filed
    March 31, 2014
    11 years ago
  • Date Published
    October 02, 2014
    10 years ago
Abstract
Described herein are compositions and methods for controlling, inhibiting, reducing and/or preventing rotifer growth with antimicrobial peptides. Methods for removing and/or preventing rotifer infestations in algae cultivations by controlling, inhibiting, reducing and/or preventing rotifer growth with an antimicrobial peptide (AMP) are further provided. Also described are transgenic algae comprising an expression vector comprising a nucleic acid sequence encoding an AMP. In some instances, the nucleic acid sequence encoding the AMP is codon-optimized for expression in algae.
Description
FIELD

The present disclosure relates generally to compositions and methods for controlling, inhibiting, reducing and/or preventing rotifer growth using peptides. The disclosure further relates to compositions and methods for removing and/or preventing rotifer infestations in algae cultivations by controlling, inhibiting, reducing and/or preventing rotifer growth with an antimicrobial peptide (AMP).


BACKGROUND

The booming global population, combined with rising industrialization and modernization generates increasing demands for energy, most of which comes from fossil fuels. Increasing greenhouse gas (GHG) emissions are accelerating climate change at a pace that has global environmental and security implications. To mitigate domestic energy demands and their environmental impacts, it is necessary to seek alternative energy sources that reduce or ameliorate carbon emissions. The potential for reductions in GHG emissions (environment), reduced fuel prices (economics), and reduction in dependency on foreign oil (national security) have driven increased scientific, public, political and commercial interests in biofuels. However, a number of limitations impede the advancement and scale-up of current biomass/biofuel production systems, including biocontamination, which has a major impact on algal crop yields, particularly in open pond systems.


Beyond bacteria, virus, fungi and protozoans that potentially cause harm to algal crops, there are other biocontaminants or ‘predators’ that effect algal crop yield in open ponds. One such organism is a small multicellular invertebrate organism called a rotifer. Rotifers are microscopic aquatic organisms found largely in freshwater ponds and in some marine environments. They can also be found in moist soil, on mosses and lichens growing on tree trunks and rocks, in rain gutters and puddles, in soil or leaf litter, on mushrooms growing near dead trees, in tanks of sewage treatment plants, and even on freshwater crustaceans and aquatic insect larvae. Their ubiquitous existence provides them easy access to algal cultivation ponds through rainwater runoff or even by wind gusts that can carry them to the ponds. They are highly adapted, hardy organisms that can withstand seasonal variations in ponds ranging from cold winters to hot summers (Sahuquillo and Miracle, Limnetica 29(1): 75-92, 2010). They have the ability to acquire genetic materials from their environment through horizontal gene transfer. Indeed, the genetic heterogeneity and complexity of these organisms was well established in a sequencing study (Gladyshev et al., Science, 320(5880):1210-1213, 2008).


Generally omnivorous, rotifers feed on dead and decaying matter and on unicellular green algae. Given the abundance of algae in open algal ponds, once rotifers enter these ponds, they seem to readily thrive by feeding upon algae and multiplying in great numbers, causing large algal biomass loss. To alleviate rotifer infestation, ponds must be drained and decontaminated with abrasive agents such as hypochlorite or other caustic agents before reestablishing open pond algal cultivation. This procedure results in large and crippling economic losses and could greatly jeopardize the reliable yields of algal crop for fuel production.


Therefore, there continues to be a need for compositions and methods to control and/or prevent rotifer contaminations in algae cultivations in order to improve biomass production systems, particularly large-scale systems.


SUMMARY

The present disclosure meets such needs by identifying and utilizing peptides to control, inhibit, reduce and/or prevent rotifer infestations without causing harm to the algae.


The present disclosure describes compositions and methods for removing and/or inhibiting and/or preventing rotifer infestations in algae cultivations by controlling, inhibiting, reducing and/or preventing rotifer growth with an antimicrobial peptide (AMP).


In one aspect, the disclosure provides a method for inhibiting the growth or inhibiting the growth rate of one or more rotifers comprising contacting one or more rotifers with an isolated antimicrobial peptide (AMP), wherein the growth or growth rate of the one or more rotifers is inhibited by the AMP compared to the growth or growth rate of the one or more rotifers absent the AMP.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMP is from about 0.5 μM to about 500 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490 or 500 μM) or from about 75 μM to about 370 μM (or from about 75, 85, 95, 105, 115, 125, 135, 145, 155, 165, 175, 185, 195, 205, 215, 225, 235, 245, 255, 265, 275, 285, 295, 305, 315, 325, 335, 345, 355, 365 or 370 μM).


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the one or more rotifers are Bdelloid rotifers, Monogononta rotifers or a combination thereof. In a related aspect, the one or more rotifers are of the species Adineta vaga, Philodina acuticornis, Brachionus or any combination thereof.


In another aspect, the disclosure provides for a method for inhibiting or preventing a rotifer infestation of an algae culture comprising contacting an algae culture with an isolated antimicrobial peptide (AMP), wherein the concentration of the AMP in the algae culture is sufficient to inhibit the growth of and/or reduce the rate of growth of the rotifer in the algae culture.


In a related aspect, the AMP does not substantially inhibit the growth of the algae. In the context of the present disclosure, “does not substantially inhibit” means inhibits less than 10%, such as less than 9%, less than 8%, less than 7%, less than 6% or less than 5%.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMP in the algae culture is from about 0.5 μM to about 500 μM or from about 75 μM to about 370 μM.


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the rotifers are Bdelloid rotifers, Monogononta rotifers or a combination thereof. In a related aspect, the rotifers are of the species Adineta vaga, Philodina acuticornis, Brachionus or any combination thereof.


In another aspect, the disclosure provides for a composition comprising a rotifer and an antimicrobial peptide (AMP). In a related aspect, the growth of the rotifer is inhibited by the AMP compared to the growth of the rotifer absent the AMP. In yet another related aspect, the growth rate of the rotifer is reduced by the presence of the AMP compared to the growth rate of the rotifer absent the AMP.


In another aspect, the composition further comprises algae. In a related aspect, the AMP does not substantially inhibit the growth of the algae. In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMP is from about 0.5 μM to about 500 μM or from about 75 μM to about 370 μM.


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the rotifer is a Bdelloid rotifers or a Monogononta rotifer. In a related aspect, the rotifer is of the species Adineta vaga, Philodina acuticornis, or Brachionus.


In another aspect, the disclosure provides for a composition comprising a transgenic algae and a rotifer, wherein the transgenic algae comprises an expression vector comprising a promoter (such as a heterologous promoter) operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP).


In another aspect, the growth of the rotifer is inhibited by the AMP compared to the growth of the rotifer absent the AMP. In a related aspect, the growth rate of the rotifer is reduced by the presence of the AMP compared to the growth rate of the rotifer absent the AMP.


In another aspect, the AMP does not substantially inhibit the growth of the algae.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the rotifer is a Bdelloid rotifer or a Monogononta rotifer. In a related aspect, the rotifer is of the species Adineta vaga, Philodina acuticornis, or Brachionus.


In another aspect, the nucleotide sequence encoding the antimicrobial peptide (AMP) comprises any one of SEQ ID NOs: 1648-1651.


In another aspect, the disclosure provides a transgenic algae comprising an expression vector, wherein the expression vector comprises a promoter, such as a heterologous promoter, operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP). In some aspects, the nucleotide sequence encoding the AMP is codon-optimized for expression in algae. In some aspects, the AMP does not substantially inhibit the growth of the algae.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP.


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the nucleotide sequence encoding the AMP comprises any one of SEQ ID NOs: 1648-1651.


In another aspect, the present disclosure provides an expression vector comprising a promoter, such as a heterologous promoter, operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP), wherein the nucleotide sequence is codon-optimized for expression in algae. In a related aspect, the nucleotide sequence encoding the AMP comprises any one of SEQ ID NOs: 1648-1651.


The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.





BRIEF DESCRIPTION OF THE DRAWINGS


FIGS. 1A-1F show microscopic images of side-by-side comparison of AMP treated and AMP untreated Adineta vaga, Philodina acuticornis and Brachionus rotifers. FIGS. 1A, 1C and 1E show a 20× magnification of Adineta vaga, Philodina acuticornis and Brachionus (untreated), respectively. FIGS. 1B, 1D and 1F show a 20× magnification of Adineta vaga, Philodina acuticornis and Brachionus (AMP treated), respectively. The rotifers in FIGS. 1B, 1D and 1F had limited to no mobility; the morphology of the rotifers treated with AMPs compared to the untreated rotifers (FIGS. 1A, 1C and 1E) indicates that the rotifers are unhealthy and/or dead.



FIG. 2 shows a schematic diagram of the pCPSR24 plasmid suitable for engineering algae with codon-optimized AMP nucleotide sequences. The nucleotide sequences of several exemplary AMPs that may be expressed with the expression vector are set forth herein as SEQ ID NOs: 1648-1651.





SEQUENCE LISTING

The nucleic and amino acid sequences listed in the accompanying sequence listing are shown using standard letter abbreviations for nucleotide bases, and three letter code for amino acids, as defined in 37 C.F.R. 1.822. Only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand. The Sequence Listing is submitted as an ASCII text file, created on Mar. 12, 2014, 716 KB, which is incorporated by reference herein. In the accompanying sequence listing:


SEQ ID NOs: 1-1647 are amino acid sequences of antimicrobial peptides (AMPs).


SEQ ID NOs: 1648-1651 are nucleotide sequences encoding AMPs, codon optimized for expression in C. protothecoides.


DETAILED DESCRIPTION
I. Terms and Methods

Unless otherwise noted, technical terms are used according to conventional usage. Definitions of common terms in molecular biology may be found in Benjamin Lewin, Genes V, published by Oxford University Press, 1994 (ISBN 0-19-854287-9); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); and Robert A. Meyers (ed.), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8).


In order to facilitate review of the various embodiments of the disclosure, the following explanations of specific terms are provided:


Algae: Refers to algae species that can be used with the compositions and methods described herein and include for example, Achnanthes orientalis, Agmenellum spp., Amphiprora hyaline, Amphora coffeiformis, Amphora coffeiformis var. linea, Amphora coffeiformis var. punctata, Amphora coffeiformis var. taylori, Amphora coffeiformis var. tenuis, Amphora delicatissima. Amphora delicatissima var. capitata, Amphora sp., Anabaena, Ankistrodesmus, Ankistrodesmus falcatus, Boekelovia hooglandii, Borodinella sp., Botryococcus braunii, Botryococcus sudeticus, Bracteococcus minor, Bracteococcus medionucleatus, Carteria, Chaetoceros gracilis, Chaetoceros muelleri, Chaetoceros muelleri var. subsalsum, Chaetoceros sp., Chlamydomas perigranulata, Chlore lla anitrata, Chlorella antarctica, Chlorella aureoviridis, Chlorella Candida, Chlorella capsulate, Chlorella desiccate, Chlorella ellipsoidea, Chlorella emersonii, Chlorella fusca, Chlorella fusca var. vacuolata, Chlorella glucotropha, Chlorella infusionum, Chlorella infusionum var. actophila, Chlorella infusionum var. auxenophila, Chlorella kessleri, Chlorella lobophora, Chlorella luteoviridis, Chlorella luteoviridis var. aureoviridis, Chlorella luteoviridis var. lutescens, Chlorella miniata, Chlorella minutissima, Chlorella mutabilis, Chlorella nocturna, Chlorella ovalis, Chlorella parva, Chlorella photophila, Chlorella pringsheimii, Chlorella protothecoides, Chlorella protothecoides var. acidicola, Chlorella regularis, Chlorella regularis var. minima, Chlorella regularis var. umbricata, Chlorella reisiglii, Chlorella saccharophila, Chlorella saccharophila var. ellipsoidea, Chlorella salina, Chlorella simplex, Chlorella sorokiniana, Chlorella sp., Chlorella sphaerica, Chlorella stigmatophora, Chlorella vanniellii, Chlorella vulgaris, Chlorella vulgaris fo. tenia, Chlorella vulgaris var. autotrophica, Chlorella vulgaris var. viridis, Chlorella vulgaris var. vulgaris, Chlorella vulgaris var. vulgaris fo. tenia, Chlorella vulgaris var. vulgaris fo. viridis, Chlorella xanthella, Chlorella zofingiensis, Chlorella trebouxioides, Chlorella vulgaris, Chlorococcum infusionum, Chlorococcum sp., Chlorogonium, Chroomonas sp., Chrysosphaera sp., Cricosphaera sp., Crypthecodinium cohnii, Cryptomonas sp., Cyclotella cryptica, Cyclotella meneghiniana, Cyclotella sp., Chlamydomonas moewusii Chlamydomonas reinhardtii Chlamydomonas sp. Dunaliella sp., Dunaliella bardawil, Dunaliella bioculata, Dunaliella granulate, Dunaliella maritime, Dunaliella minuta, Dunaliella parva, Dunaliella peircei, Dunaliella primolecta, Dunaliella salina, Dunaliella terricola, Dunaliella tertiolecta, Dunaliella viridis, Dunaliella tertiolecta, Eremosphaera viridis, Eremosphaera sp., Ellipsoidon sp., Euglena spp., Franceia sp., Fragilaria crotonensis, Fragilaria sp., Gleocapsa sp., Gloeothamnion sp., Haematococcus pluvialis, Hymenomonas sp., Isochrysis aff. galbana, Isochrysis galbana, Lepocinclis, Micractinium, Micractinium, Monoraphidium minutum, Monoraphidium sp., Nannochloris sp., Navicula acceptata, Navicula biskanterae, Navicula pseudotenelloides, Navicula pelliculosa, Navicula saprophila, Navicula sp., Nephrochloris sp., Nephroselmis sp., Nitschia communis, Nitzschia alexandrina, Nitzschia closterium, Nitzschia communis, Nitzschia dissipata, Nitzschia frustulum, Nitzschia hantzschiana, Nitzschia inconspicua, Nitzschia intermedia, Nitzschia microcephala, Nitzschia pusilla, Nitzschia pusilla elliptica, Nitzschia pusilla monoensis, Nitzschia quadrangular, Nitzschia sp., Ochromonas sp., Oocystis parva, Oocystis pusilla, Oocystis sp., Oscillatoria limnetica, Oscillatoria sp., Oscillatoria subbrevis, Parachlorella kessleri, Pascheria acidophila, Pavlova sp., Phaeodactylum tricomutum, Phagus, Phormidium, Platymonas sp., Pleurochrysis carterae, Pleurochrysis dentate, Pleurochrysis sp., Prototheca wickerhamii, Prototheca stagnora, Prototheca portoricensis, Prototheca moriformis, Prototheca zopfii, Pseudochlorella aquatica, Pyramimonas sp., Pyrobotrys, Rhodococcus opacus, Sarcinoid chrysophyte, Scenedesmus armatus, Schizochytrium, Spirogyra, Spirulina platensis, Stichococcus sp., Synechococcus sp., Synechocystisf, Tagetes erecta, Tagetes patula, Tetraedron, Tetraselmis sp., Tetraselmis suecica, Thalassiosira weissflogii, and Viridiella fridericiana.


Antimicrobial peptide (AMP): A naturally occurring or synthetic linear, branched or cyclic peptide, or a peptide having a linear, branched and/or cyclic structure that generally kills, prevents and/or inhibits the growth of a microorganism.


Biocompatible: Synthetic and/or natural material that does not have a substantial negative impact on organisms, tissues, cells, biological systems or pathways and/or protein function.


Biomass: Any algal-based organic matter that may be used for carbon storage and/or as a source of energy (e.g., biofuels).


Codon-optimized: A “codon-optimized” nucleic acid refers to a nucleic acid sequence that has been altered such that the codons are optimal for expression in a particular system (such as a particular species or group of species). For example, a nucleic acid sequence can be optimized for expression in plant cells, for example, in algae. Codon optimization does not alter the amino acid sequence of the encoded protein.


Contacting: Placement in direct physical association; includes both in solid and liquid form.


Growth rate reduction (or reducing rate of growth): Reducing the rate of growth of an individual organism or a population of organisms. Growth rate reduction may include reducing or decreasing, directly or indirectly, the rate at which an organism acquires mass or the rate at which a population of organisms acquires mass (e.g., by stopping (directly or indirectly) ingestion, digestion and/or assimilation of food by the organism) and/or the reproduction of an organism. In the case of rotifers, measuring growth rate reduction may include, but is not limited to, one or more of the following and as compared to rotifers in normal growth conditions: a decrease in motility (e.g., swimming or cilia movement) of the rotifer(s), a decrease in ingestion of algae by rotifer(s), a decrease in the rate of egg production and/or reproduction, a decrease in the rate of feeding, and a decrease in the rate of growth (e.g., size and/or mass) of rotifer(s).


Inhibiting growth (or growth inhibition): Preventing growth of an individual organism or a population of organisms. Growth inhibition may be as extreme as death or killing of the organism or population of organisms, or may include preventing, directly or indirectly, an increase in the mass of an organism or population of organisms (e.g., by stopping, directly or indirectly, ingestion, digestion and/or assimilation of food by the organism) and/or the reproduction of an organism. In the case of rotifers, measuring growth inhibition may include, but is not limited to, one or more of the following and as compared to rotifers in normal growth conditions: an inhibition of movement (e.g., swimming or cilia movement) of the rotifer(s), an inhibition of ingestion of algae by rotifer(s), an inhibition of the rate of egg production and/or reproduction of rotifer(s), and an inhibition of feeding by rotifer(s).


Insecticidal: Capable of killing and/or controlling insects. In the context of the present disclosure, an “insecticidal AMP” is an AMP belonging to a class of AMPs that have activity against insects (i.e. are capable of killing and/or controlling insects). As used herein, a “non-insecticidal AMP” is any AMP belonging to a recognized class of AMPs other than the insecticidal class. For example, non-insecticidal AMPs include anticancer/tumor AMPs, anti-protist AMPs, antiparasitic AMPs, spermicidal AMPs, anti-HIV-1 AMPs and chemotactic AMPs.


Microorganism: Microscopic single cell or multicellular organism. Non-limiting examples of microorganisms include bacteria, protozoa, fungi, rotifers, planarians and viruses.


Minimal inhibitory concentration (MIC): The lowest concentration of an antimicrobial peptide (e.g., AMP) that will inhibit the visible growth of an organism (e.g., algae).


Operably linked: A first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Generally, operably linked DNA sequences are contiguous and, where necessary to join two protein-coding regions, in the same reading frame.


Percent identity: In the context of two or more nucleic acids or peptide sequences, refers to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured, for example, using a BLAST or BLAST 2.0 sequence comparison algorithm with default parameters described below, or by manual alignment and visual inspection.


Promoter: A region of DNA that directs/initiates transcription of a nucleic acid (e.g. a gene). A promoter includes necessary nucleic acid sequences near the start site of transcription. Typically, promoters are located near the genes they transcribe. A promoter also optionally includes distal enhancer or repressor elements which can be located as much as several thousand base pairs from the start site of transcription.


Rotifers: Microscopic, multicellular, pseudocoelomate animals of the phylum Rotifera. Rotifers can be found in many freshwater environments and in moist soil. Some rotifer species can be found in saltwater.


Transgenic algae: Algae whose genetic material has been altered using genetic engineering techniques so that it is no longer a “wild type” organism. An example of genetically modified algae is transgenic algae that possess one or more genes that have been transferred to the algae from a different species. Another example is an alga wherein endogenous genes have been rearranged such that they are in a different and advantageous arrangement or amplified so that specific sequences are increased. In this example, no foreign DNA remains in the modified cell.


Vector: A vector is a nucleic acid molecule allowing insertion of foreign nucleic acid without disrupting the ability of the vector to replicate and/or integrate in a host cell. A vector can include nucleic acid sequences that permit it to replicate in a host cell, such as an origin of replication. A vector can also include one or more selectable marker genes and other genetic elements. An expression vector is a vector that contains the necessary regulatory sequences to allow transcription and translation of inserted gene or genes.


Wild-type: The phenotype of the typical form of a species as it occurs in nature.


Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise. “Comprising A or B” means including A, or B, or A and B. It is further to be understood that all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for description.


Further, ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50 (as well as fractions thereof unless the context clearly dictates otherwise). Any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated. Also, any number range recited herein relating to any physical feature, such as polymer subunits, size or thickness, are to be understood to include any integer within the recited range, unless otherwise indicated. As used herein, “about” or “consisting essentially of” mean±20% of the indicated range, value, or structure, unless otherwise indicated. As used herein, the terms “include” and “comprise” are open ended and are used synonymously. It should be understood that the terms “a” and “an” as used herein refer to “one or more” of the enumerated components. The use of the alternative (e.g., “or”) should be understood to mean either one, both, or any combination thereof of the alternatives


Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including explanations of terms, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.


II. Overview of Several Embodiments

The present disclosure relates generally to compositions and methods for controlling, inhibiting, reducing and/or preventing rotifer growth using peptides. More specifically the disclosure relates to removing and/or preventing rotifer infestations in algae cultivations by the expression of one or more antimicrobial peptides (AMPs) by transgenic algae and/or the introduction of one or more AMPs in an algae cultivation (e.g., open-pond system). The present disclosure also provides expression vectors comprising a heterologous promoter operably linked to a nucleotide sequence encoding an AMP, as well as transgenic algae comprising the expression vectors.


Novel aspects of the present disclosure include the use of biomolecules (e.g., AMPs) to control, reduce and/or prevent the growth of metazoan organisms such as rotifers. This disclosure provides the utility of AMPs in controlling rotifer populations (e.g., controlling, inhibiting, reducing, prevent and/or killing) by engineering algae to express one or more of these peptides in the algae of choice to confer innate defense capabilities against these indiscriminate algae grazers. There are thousands of natural AMPs that have been identified thus far (see e.g., the Antimicrobial Peptide Database, which is available online).


Additional embodiments include a method for inhibiting the growth of one or more rotifers comprising contacting one or more rotifers with an isolated antimicrobial peptide (AMP), wherein the growth of the one or more rotifers is inhibited by the AMP compared to the growth of the one or more rotifers absent the AMP.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMP is from about 0.5 μM to about 1000 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990 or 1000 μM).


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the one or more rotifers are Bdelloid rotifers, Monogononta rotifers or a combination thereof. In a related aspect, the one or more rotifers are of the species Adineta vaga, Philodina acuticornis, Brachionus or any combination thereof.


In another aspect, the disclosure provides for a method for reducing the growth rate of one or more rotifers comprising contacting one or more rotifers with an isolated antimicrobial peptide (AMP), wherein the growth rate of the one or more rotifers is reduced by the presence of the AMP compared to the growth rate of the one or more rotifers absent the AMP.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMP is from about 0.5 μM to about 1000 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990 or 1000 μM).


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the one or more rotifers are Bdelloid rotifers, Monogononta rotifers or a combination thereof. In a related aspect, the one or more rotifers are of the species Adineta vaga, Philodina acuticornis, Brachionus or any combination thereof.


In another aspect, the disclosure provides for a composition comprising a rotifer and an antimicrobial peptide (AMP). In a related aspect, the growth of the rotifer is inhibited by the AMP compared to the growth of the rotifer absent the AMP. In yet another related aspect, the growth rate of the rotifer is reduced by the presence of the AMP compared to the growth rate of the rotifer absent the AMP.


In another aspect, the composition further comprises algae. In a related aspect, the AMP does not substantially inhibit the growth of the algae. In the context of the present disclosure, “does not substantially inhibit” means inhibits less than 10%, such as less than 9%, less than 8%, less than 7%, less than 6% or less than 5%. In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMP is from about 0.5 μM to about 1000 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990 or 1000 μM).


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the rotifers are Bdelloid rotifers, Monogononta rotifers or a combination thereof. In a related aspect, the rotifers are of the species Adineta vaga, Philodina acuticornis, Brachionus or any combination thereof.


In another aspect, the disclosure provides for a method for preventing a rotifer infestation of an algae culture comprising contacting an algae culture with an isolated antimicrobial peptide (AMP), wherein the concentration of the AMP in the algae culture is sufficient to inhibit the growth of and/or reduce the rate of growth of a rotifer in the algae culture.


In a related aspect, the AMP does not substantially inhibit the growth of the algae.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP. In a related aspect, the concentration of the AMPin the algae culture is from about 0.5 μM to about 1000 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800, 810, 820, 830, 840, 850, 860, 870, 880, 890, 900, 910, 920, 930, 940, 950, 960, 970, 980, 990 or 1000 μM).


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the rotifers are Bdelloid rotifers, Monogononta rotifers or a combination thereof. In a related aspect, the rotifers are of the species Adineta vaga, Philodina acuticornis, Brachionus or any combination thereof.


In another aspect, the disclosure provides a transgenic algae comprising an expression vector, wherein the expression vector comprises a promoter, such as as heterologous promoter, operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP). In some aspects, the nucleotide sequence encoding the AMP is codon-optimized for expression in algae. In some aspects, the AMP does not substantially inhibit the growth of the algae.


In another aspect, the AMP is from about 5 to about 200 amino acids in length. In another aspect, the AMP is from about 5 to about 600 amino acids in length. In a related aspect, the AMP is an insecticidal AMP or a non-insecticidal AMP.


In another aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647. In a related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647. In yet another related aspect, the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.


In another aspect, the nucleotide sequence encoding the AMP comprises any one of SEQ ID NOs: 1648-1651.


In another aspect, the present disclosure provides an expression vector comprising a promoter, such as as heterologous promoter, operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP), wherein the nucleotide sequence is codon-optimized for expression in algae. In a related aspect, the nucleotide sequence encoding the AMP comprises any one of SEQ ID NOs: 1648-1651.


A. Antimicrobial Peptides (AMPs)


AMPs are a class of peptides that demonstrate antimicrobial activity against microorganisms. Generally, these peptides may be naturally occurring or synthetic and range in size from about 5 amino acids to about 200 amino acids in length (or 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199 or 200 amino acids in length). In most cases, the peptides range in size from about 12 amino acids to about 75 amino acids in length (or 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74 or 75 amino acids in length). In other cases, the AMP is from about 5 to about 600 amino acids in length. These peptides typically comprise two or more positively charged amino acids. Non-limiting examples of amino acid residues that may provide a positive charge include arginine, lysine and histidine. Further, these peptides may be amphipathic. The peptides may comprise a hydrophobic domain, resulting from the presence of hydrophobic amino acid residues. The peptides may comprise at least about 30% hydrophobic residues, 40% hydrophobic residues, 50% hydrophobic residues, 60% hydrophobic residues, 70% hydrophobic residues, 80% hydrophobic residues or 90% hydrophobic residues. The peptides may comprise a linear chain of amino acids, a region of branched amino acids and/or cyclic region of amino acids. An example cyclic peptide includes, but is not limited to, peptides produced by non-ribosomal peptide synthetase (NRPS) (e.g., cyanobacteria derived peptides) or mixed system of NRPS and polyketide synthetases.


In certain aspects, the concentration of the AMP (such as the concentratin of the AMP in an algae culture) is from about 0.5 μM to about 50 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50). In a related aspect, the concentration of the AMP is from about 0.5 μM to about 500 μM (or from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490 or 500 μM).


The mechanisms by which AMPs act varies and may include disrupting membranes, interfering with metabolism and targeting cytoplasmic components. The initial contact between the peptide and the target organism is electrostatic, as most bacterial surfaces are anionic, or hydrophobic, such as in the antimicrobial peptide Piscidin. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by ‘barrel-stave,’ ‘carpet’ or ‘toroidal-pore’ mechanisms. Alternately, they may penetrate into the cell to bind intracellular molecules which are crucial to cell living. Intracellular binding models include inhibition of cell wall synthesis, alteration of the cytoplasmic membrane, activation of autolysin, inhibition of DNA, RNA, and protein synthesis, and inhibition of certain enzymes. However, in many cases, the exact mechanism of killing is not known. In contrast to many conventional antibiotics, the activity of these peptides appears to be bactericidal (bacteria killer) instead of bacteriostatic (bacteria growth inhibitor). In general, the antimicrobial activity of these peptides is determined by measuring the minimal inhibitory concentration (MIC), which is the lowest concentration of drug that inhibits bacterial growth.


In addition to exhibiting antimicrobial activity, these peptides have shown to have a number of immunomodulatory functions that may be involved in the clearance of infection, including the ability to alter host gene expression, act as chemokines and/or induce chemokine production, inhibiting lipopolysaccharide induced pro-inflammatory cytokine production, promoting wound healing, and modulating the responses of dendritic cells and cells of the adaptive immune response. Animal models indicate that host defense peptides are crucial for both prevention and clearance of infection. It appears as though many peptides initially isolated as and termed “antimicrobial peptides” have been shown to have more significant alternative functions in vivo (e.g., hepcidin).


The amino acid sequences of exemplary AMPs are provided below in Table 1. An “X” in an amino acid sequence indicates that the amino acid residue at that position of the peptide may be any amino acid residue.










TABLE 1





SEQ ID NO:
AMINO ACID SEQUENCE
















1
SIGTAVKKAVPIAKKVGKVAIPIAKAVLSVVGQLVG





2
ELDRICGYGTARCRKKCRSQEYRIGRCPNTYACCLRKWDESLLNRTKP





3
GLKDKFKSMGEKLKQYIQTWKAKF





5
RFRPPIRRPPIRPPFYPPFRPPIRPPIFPPIRPPFRPPLRFP





6
ICIFCCGCCHRSKCGMCCKT





7
FLSLLPSIVSGAVSLAKKLG





8
VRPYLVAF





9
KTCENLADTY





10
GPLSCRRNGGVCIPIRCPGPMRQIGTCFGRPVKCCRSW





11
FLPIIAKLLGGLL





12
FLPIPRPILLGLL





13
FLIIRRPIVLGLL





14
GLHKVMREVLGYERNSYKKFFLR





15
INWKKIAEVGGKILSSL





16
INWKGIAAMAKKLL





17
INWKKIAEIGKQVLSAL





18
INWKGIAAMKKLL





19
SNDIYFNFQR





20
FLPMLAGLAANFLPKLFCKITKKC





21
FLPLAVSLAANFLPKLFCKITKKC





22
FLPMLAGLAANLLPKLFCKITKKC





23
FLPMLAGLAANFLPELFCKITKKC





24
FLPIVGKLLSGLSGLL





25
FLPIVGKLLSGLL





26
LLPIVGKLLSGLL





27
IDWKKLLDAAKQIL





28
ILGTILGLLKSL





29
KQATVGDINTERPGILDLKGKAKWDAWNGLKGTSKEDAMKAYINKVEELK



KKYGI





30
RPRPNYRPRPIYRP





31
GLLSVLGSVAKHVLPHVVPVIAEKL





32
FLPLIGRVLSGIL





33
LLPILGNLLNGLL





34
LLPIVGNLLNSLL





35
VLPIIGNLLNSLL





36
FLPLIGKVLSGIL





37
RNIICLMQHGTCRLFFCRSGEKKSEICSDPWNRCCI





38
GLWSTIKNVGKEAAIAAGKAALGAL





39
NLYQFKNMIQCAGTQLCVAYVKYGCYCGPGGTGTPLDQLDRCCQTHDHCY



DNAKKFGNCIPYFKTYEYTCNKPDLTCTDAKGSCARNVCDCDRAAAICFAA



APYNLANFGINKETHCQ





41
GIGASILSAGKSALKGLAKGLAEHFAN





42
GIGSAILSAGKSALKGLAKGLAEHFAN





43
GIGAAILSAGKSALKGLAKGLAEHF





45
GIGGALLSAAKVGLKGLAKGLAEHFAN





46
SMWSGMWRRKLKKLRNALKKKLKGE





47
GLFGKLIKKFGRKAISYAVKKARGKH





48
GLFGKLIKKFGRKAISYAVKKARGKN





49
SWKSMAKKLKEYMEKLKQRA





50
SWASMAKKLKEYMEKLKQRA





51
GLKDKFKSMGEKLKQYIQTWKAKF





52
SLKDKVKSMGEKLKQYIQTWKAKF





53
GFFGKMKEYFKKFGASFKRRFANLKKRL





54
TKYYGNGVYCNSKKCWVDWGTAQGCIDVVIGQLGGGIPGKGKC





55
AGETHTVMINHAGRGAPKLVVGGKKLS





56
SDEKASPDRHHRFSLSRYAKLANRLSKWIGNRGNRLANPKLLETFKSV





57
SWLSKTAKKLENSAKKRISEGIAIAIQGGPR





58
WNPFKELERAGQRVRDAVISAAPAVATVGQAAAIARG





59
WNPFKELERAGQRVRDAIISAGPAVATVGQAAAIARG





60
WNPFKELERAGQRVRDAIISAAPAVATVGQAAAIARG





61
WNPFKELERAGQRVRDAVISAAAVATVGQAAAIARGG





62
KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK





63
KWKIFKKIEKVGRNIRNGIIKAGPAVAVLGEAKAL





64
KWKVFKKIEKMGRNIRNGIVKAGPAIAVLGEAKAL





65
WNPFKELERAGQRVRDAIISAGPAVATVAQATALAK





66
WNPFKELEKVGQRVRDAVISAGPAVATVAQATALAK





67
LSCKRGTCHFGRCPSHLIKGSCSGG





68
RRIRPRPPRLPRPRPRPLPFPRPGPRPIPRPLPFPRPGPRPIPRPLPFPRPGPRP





69
VRNHVTCRINRGFCVPIRCPGRTRQIGTCFGPRIKCCRSW





70
VRNFVTCRINRGFCVPIRCPGHRRQIGTCLGPQIKCCR





71
GPLSCGRNGGVCIPIRCPVPMRQIGTCFGRPVKCCRSW





72
SGISGPLSCGRNGGVCIPIRCPVPMRQIGTCFGRPVKCCRSW





73
SLQGGAPNFPQPSQQNGGWQVSPDLGRDDKGNTRGQIEIQNKGKDHDFNAG



WGKVIRGPNKAKPTWHVGGTYRR





75
DCLSGRYKGPCAVWDNETCRRVCKEEGRSSGHCSPSLKCWCEGC





76
SLFSLIKAGAKFLGKNLLKQGACYAACKASKQC





77
GIMSIVKDVAKNAAKEAAKGALSTLSCKLAKTC





78
GIMSIVKDVAKTAAKEAAKGALSTLSCKLAKTC





79
FLPLLAGLAANFLPTIICKISYKC





81
GLRKRLRKFRNKIKEKLKKI





82
FLPLILRKIVTAL





83
LRDLVCYCRSRGCKGRERMNGTCRKGHLLYTLCCR





84
VVCACRRALCLPRERRAGFCRIRGRIHPLCCRR





85
VVCACRRALCLPLERRAGFCRIRGRIHPLCCRR





86
GFGCPLDQMQCHRHCQTITGRSGGYCSGPLKLTCTCYR





87
ACAAHCLLRGNRGGYCNGKG





89
FLPLLASLFSRLL





90
FLPLIGKILGTILGK





91
FLPLLASLFSRLF





92
FLPVILPVIGKLLNGILGK





94
ISDYSIAMDKIRQQDFVNWLLAQKGKKSDWKHNITQ





95
KAVAAKKSPKKAKKPATPKKAAKSPKKVKKPAAAAKKAAKSPKKATKAAK



PKAAKPKAAKAKKAAPKKK





96
FLPLLFGAISHLL





97
AERVGAGAPVYL





98
FLPLVRGAAKLIPSVVCAISKRC





99
GFSSLFKAGAKYLLKSVGKAGAQQLACKAANNCA





100
GVITDALKGAAKTVAAELLRKAHCKLTNSC





101
SIWEGIKNAGKGFLVSILDKVRCKVAGGCNP





102
GLFSVLGSVAKHLLPHVAPIIAEKL





103
GLFSVLGSVAKHLLPHVVPVIAEKL





104
GLFKVLGSVAKHLLPHVAPIIAEKL





105
GLWEKVKEKANELVSGIVEGVK





106
GLFSKFNKKKIKSGLIKIIKTAGKEAGLEALRTGIDVIGCKIKGEC





107
GLFSKFNKKKIKSGLFKIIKTAGKEAGLEALRTGIDVIGCKIKGEC





108
GFFSLIKGVAKIATKGLAKNLGKMGLDLVGCKISKEC





109
VIDDLKKVAKKVRRELLCKKHHKKLN





110
GFISTVKNLATNVAGTVIDTIKCKVTGGC





111
AIMDTIKDTAKTVAVGLLNKLKCKITGC





112
GIMDTIKDTAKTVAVGLLNKLKCKITGC





113
DSHAKRHHGYKRKFHEKHHSHRGYRSNYLYDN





114
ALLHHGLNCAKGVLA





115
WLNALLHHGLNCAKGVLA





116
GILDTIKSIASKVWNSKTVQDLKRKGINWVANKLGVSPQAA





117
ITSISLCTPGCKTGALMGCNMKTATCHCSIHVSK





120
QVVRNPQSCRWNMGVCIPISCPGNMRQIGTCFGPRVPCCR





121
GIGKFLHSAGKFGKAFVGEIMKS





122
GIGKFLHSAKKFGKAFVGEIMNS





123
RSGRGECRRQCLRRHEGQPWETQECMRRCRRRG





124
ACHAHCQSVGRRGGYCGNFRMTCYCY





125
NCIQQCVSKGAQGGYCTNEKCTCY





126
GRFKRFRKKFKKLFKKLS





127
GGLRSLGRKILRAWKKYG





128
FAEPTBSEEEGESYSKEVPEMEKRYGGFM





129
AELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIATLKDGRKICLDPDAPR



IKKIVQKKLAGD





130
RRWCFRVCYRGFCYRKCR





131
RRWCFRVCYKGFCYRKCR





132
FCTMIPIPRCY





133
RVCFAIPLPICH





134
RVCYAIPLPICY





135
RVCYAIPLPIC





136
SIGSALKKALPVAKKIGKIALPIAKAALP





137
GWLKKIGKKIERVGQHTRDATIQGLGIAQQAANVAATAR





138
GWLKKIGKKIERVGQHTRDATIQVIGVAQQAANVAATAR





139
GWLRKIGKKIERVGQHTRDATIQVLGIAQQAANVAATAR





140
GWIRDFGKRIERVGQHTRDATIQTIAVAQQAANVAATLKG





141
QGVRNHVTCRIYGGFCVPIRCPGRTRQIGTCFGRPVKCCRRW





142
QGVRNFVTCRINRGFCVPIRCPGHRRQIGTCLGPRIKCCR





143
RRCICTTRTCRFPYRRLGTCLFQNRVYTFCC





144
KWCFRVCYRGICYRRCR





145
RWCFRVCYRGICYRKCR





146
KWCFRVCYRGICYRKCR





147
NPVSCVRNKGICVPIRCPGSMKQIGTCVGRAVKCCRKK





148
AGFAAQAAASLAPVAAQQL





149
KSCCRNTWARNCYNVCRLPGTISREICAKKCDCKIISGTTCPSDYPK





150
SLGSFLKGVGTTLASVGKVVSDQFGKLLQAGQ





151
ALWKNMLKGIGKLAGQAALGAVKTLVGA





152
ALWKDILKNVGKAAGKAVLNTVTDMVNQ





153
GWMSKIASGIGTFLSGMQQ





154
ACNFQSCWATCQAQHSIYFRRAFCDRSQCKCVFVRG





155
EWEPVQNGGSSYYMVPRIWA





157
GKLQAFLAKMKEIAAQTL





158
GRLQAFLAKMKEIAAQTL





159
KVNVNAIKKGGKAIGKGFKVISAASTAHDVYEHIKNRRH





160
GKIPVKAIKKGGQIIGKALRGINIASTAHDIISQFKPKKKKNH





161
KVPIGAIKKGGKIIKKGLGVIGAAGTAHEVYSHVKNRH





162
KVPIGAIKKGGKIIKKGLGVLGAAGTAHEVYNHVRNRQ





163
KVPIGAIKKGGKIIKKGLGVIGAAGTAHEVYSHVKNRQ





164
KVPVGAIKKGGKAIKTGLGVVGAAGTAHEVYSHIRNRH





165
KGIGSALKKGGKIIKGGLGALGAIGTGQQVYEHVQNRQ





166
GWASKIGQTLGKIAKVGLKELIQPK





168
FLSLIPHAINAVSAIAKHFG





169
VIGSILGALASGLPTLISWIKNR





170
AIGSILGALAKGLPTLISWIKNR





171
YYGNGVYCTKNKCTVDWAKATTCIAGMSIGGFLGG





172
NFVTCRINRGFCVPIRCPGHRRQIGTCLGPRIKCCR





173
SIITMTKEAKLPQLWKQIACRLYNTC





174
ETESTPDYLKNIQQQLEEYTKNFNTQVQNAFDSDKIKSEVNNFIESLGKILNTE



KKEAPK





175
ENFFKEIERAGQRIRDAIISAAPAVETLAQAQKIIKGGD





176
DTLIGSCVWGATNYTSDCNAECKRRGYKGGHCGSFLNVNCWCEE





177
DKLIGSCVWGATNYTSDCNAECKRRGYKGGHCGSFWNVNCWCEE





178
EADEPLWLYKGDNIERAPTTADHPILPSIIDDVKLDPNRRYA





179
DIQIPGIKKPTHRDIIIPNWNPNVRTQPWQRFGGNKS





180
EIRLPEPFRFPSPTVPKPIDIDPILPHPWSPRQTYPIIARRS





181
GLLRASSVWGRKYYVDLAGCAKA





182
SIITMTKEAKLPQSWKQIACRLYNTC





183
AALRGALRAVARVGKAILPHVAIANPYVRTPYVHNNP





184
VRRFPWWWPFLRR





185
RRRFPWVCWPFLRRR





186
RFPWWWPFLR





187
FPWWWPF





188
KWKLFKKIGIGKFLHSAKKF





189
KWKLFKKIPKFLHSAKKF





190
KLKLFKKIGIGKFLHSAKKF





191
KAKLFKKIGIGKFLHSAKKF





192
INLKAIAALAKKLLG





193
INLKAIAAMAKKLL





194
APIIRRIPYYPEVESDLRIVDCKRSEGFCQEYCNYLETQVGYCSKKKDACCLH





196
RSVCRQIKICRRRGGCYYKCTNRPY





197
XNLRRIIRKIIHIIKKYG





198
XNLRRIIRKGIHIIKKYG





199
XNLRRITRKIIHIIKKYG





200
FIGPIISALASLFG





201
FLSLALAALPKFLCLVFKKC





202
FLSLALAALPKLFCLIFKKC





203
FLPLLLAGLPKLLCLFFKKC





204
GLFDVVKGVLKGAGKNVAGSLLEQLKCKLSGGC





205
GIFDVVKGVLKGVGKNVAGSLLEQLKCKLSGGC





206
GLFSVVTGVLKAVGKNVAKNVGGSLLEQLKCKISGGC





207
YVPLPNVPQPGRRPFPTFPGQGPFNPKIKWPQGY





208
QCIGNGGRCNENVGPPYCCSGFCLRQPGQGYGYCKNR





209
CIGNGGRCNENVGPPYCCSGFCLRQPNQGYGVCRNR





210
VGECVRGRCPSGMCCSQFGYCGKGPKYCGR





211
FALALKALKKALKKLKKALKKAL





212
LRDLVCYCRTRGCKRRERMNGTCRKGHLMYTLCCR





213
LRDLVCYCRKRGCKRRERMNGTCRKGHLMYTLCCR





214
VTCDLLSFKGQVNDSACAANCLSLGKAGGHCEKVGCICRKTSFKDLWDKYF





215
AMWKDVLKKIGTVALHAGKAALGAVADTISQ





216
LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES





217
GRFKRFRKKFKKLFKKLSPVIPLLHLG





218
RIIDLLWRVRRPQKPKFVTVWVR





219
GRFRRLRKKTRKRLKKIGKVLKWIPPIVGSIPLGCG





220
GLLSRLRDFLSDRGRRLGEKIERIGQKIKDLSEFFQS





221
RRRPRPPYLPRPRPPPFFPPRLPPRIPPGFPPRFPPRFP





222
DLRFLYPRGKLPVPTPPPFNPKPIYIDMGNRY





223
VCGETCVGGTCNTPGCTCSWPVCTRNGLP





224
GIPCGESCVWIPCISAALGCSCKNKVCYRN





225
SIPCGESCVFIPCTVTALLGCSCKSKVCYKN





226
GVIPCGESCVFIPCISTLLGCSCKNKVCYRN





227
FFHHIFRGIVHVGKTIHKLVTGG





228
FFHHIFRGIVHVGKTIHRLVTGG





229
FFHHIFRGIVHVGRTIHKLVTGG





230
FFHHIFRGIVHVGRTIHRLVTGG





232
GWKDWAKKAGGWLKKKGPGMAKAALKAAMQ





233
GWKDWLKKGKEWLKAKGPGIVKAALQAATQ





234
GWKDWLNKGKEWLKKKGPGIMKAALKAATQ





235
DFKDWMKTAGEWLKKKGPGILKAAMAAAT





236
GLKDWVKIAGGWLKKKGPGILKAAMAAATQ





237
GLVDVLGKVGGLIKKLLP





238
GLVDVLGKVGGLIKKLLPG





239
LLKELWTKMKGAGKAVLGKIKGLL





240
LLKELWTKIKGAGKAVLGKIKGLL





241
WLGSALKIGAKLLPSVVGLFKKKKQ





242
WLGSALKIGAKLLPSVVGLFQKKKK





243
GIWGTLAKIGIKAVPRVISMLKKKKQ





244
GIWGTALKWGVKLLPKLVGMAQTKKQ





245
FWGALIKGAAKLIPSVVGLFKKKQ





246
FIGTALGIASAIPAIVKLFK





247
LLPNLLKSLL





248
FVQWFSKFLGRIL





249
GLFDIIKKIAESI





250
GLFDIIKKIAESF





251
FDIVKKVVGALGSL





252
GLFDIVKKVVGAIGSL





253
FDIVKKVVGTIAGL





254
GLFDIAKKVIGVIGSL





255
GLFDIVKKIAGHIVSSI





256
GLFGVLAKVAAHVVPAIAEHF





257
GLFGVLAKVASHVVPAIAEHFQA





258
KTCEHLADTYRGVCFTNASCDDHCKNKAHLISGTCHNWKCFCTQNC





259
KTCENLSGTFKGPCIPDGNCNKHCRNNEHLLSGRCRDDFRCWCTNRC





260
SSLLEKGLDGAKKAVGGLGKLGKDAVEDLESVGKGAVHDVKDVLDSV





261
ZCRRLCYKQRCVTYCRGR





262
GCRFCCNCCPNMSGCGVCCRF





263
SKGKKANKDVELARG





264
GLNTLKKVFQGLHEAIKLINNHVQ





265
GLNALKKVFQGIHEAIKLINNHVQ





266
GINTLKKVIQGLHEVIKLVSNHE





267
GINTLKKVIQGLHEVIKLVSNHA





269
FRGLAKLLKIGLKSFARVLKKVLPKAAKAGKALAKSMADENAIRQQNQ





270
GKFSVFGKILRSIAKVFKGVGKVRKQFKTASDLDKNQ





271
GKFSGFAKILKSIAKFFKGVGKVRKQFKEASDLDKNQ





272
GKLSGISKVLRAIAKFFKGVGKARKQFKEASDLDKNQ





273
GKFSVFSKILRSIAKVFKGVGKVRKQFKTASDLDKNQ





274
RWKLFKKIEKVGRNVRDGLIKAGPAIAVIGQAKSL





275
RWKIFKKIEKMGRNIRDGIVKAGPAIEVLGSAKAI





276
GVLSNVIGYLKKLGTGALNAVLKQ





277
ILPWKWPWWPWRR





278
SHQDCYEALHKCMASHSKPFSCSMKFHMCLQQQ





279
GIGTKILGGVKTALKGALKELASTYAN





280
ILGPVISTIGGVLGGLLKNL





281
GIGTKILGGVKTALKGALKELASTYVN





282
GIGGKILSGLKTALKGAAKELASTYLH





283
ILGPVLSMVGSALGGLIKKI





284
GIGGVLLSAGKAALKGLAKVLAEKYAN





285
ILGPVLGLVGNALGGLIKKI





286
SIGAKILGGVKTLLKGALKELASTYLQ





287
GLLNTFKDWAISIAKGAGKGVLTTLSCKLDKSC





288
SLFSLIKAGAKFLGKNLLKQGAQYAACKVSKEC





289
GILDSFKQFAKGVGKDLIKGAAQGVLSTMSCKLAKTC





290
LLPIVGNLLKSLL





291
VTCDILSVEAKGVKLNDAACAAHCLFRGRSGGYCNGKRVCVCR





292
SLGGVISGAKKVAKVAIPIGKAVLPVVAKLVG





293
HRHQGPIFDTRPSPFNPNQPRPGPIY





294
GSKKPVPIIYCNRRTGKCQRM





295
VTCYCRSTRCGFRERLSGACGYRGRIYRLCCR





296
GICRCICGRRICRCICGR





297
RYICRCICGRGICRCICG





298
GICRCICGRYICRCICGR





299
GICYCICGKGICRCICGR





300
RXICGXXIC





301
GVCRCICGRGVCRCICGR





302
GVCRCICGRGVCRCICRR





303
GICRCICGRRICRCICGK





304
GICKCICGRRICRCICGR





305
GICRCICGRRICKCICGR





306
GICRCICGRKICRCICGR





307
GICRCICGKKICRCICGR





308
GICRCICGKRICRCICGR





309
GICKCICGKGICKCICGR





310
GICRCICGKGICRCYCGR





311
VTPAMRTFALLTAMLLLVALAQAEPLQARADEAAAQEQPGADDQEMAHAFT



WHESAALPLSSDSARGLRCICGRGICRLLRRFGSCAFRGTLHRICCRACRIKKH



KLRIYFESKKFLLLLYLVLHFLFSSKINTLLQDFSL





312
VTPAMRTFALLTAMLLLVALAQAEPLQARADEAAAQEQPGADDQEMAHAFT



WHESAALPLSSDSARGLRCICGRRICRLLRRFGSCAFRGTLHRICCRACRIKKH



KLRIYFESKKFLLLLYLVLHFLFSSKINTLLQDFS





313
VTPAMRTFALLTAMLLLVALAQAEPLQARADEAAAQEQSDSARGLRCICGRG



ICRLLRRFGSCAFRGTLHRVCCRTCRIKKNKLRIYFESKKFLLLLYLVLHFLFSS



KINTLLQDFSL





314
RCLCVLRIC





315
RCLCVLRVC





316
RCLCTLRIC





317
RCLCTLRVC





318
RCLCGLRIC





319
RCLCGLRVC





320
RCICVLRFC





321
RCICVLRVC





322
RCICTLRFC





323
RCICTLRVC





324
RCICRLRFC





325
RCICRLRVC





326
RCICGRRIC





327
RCLCVRRVC





328
RCLCTRRFC





329
RCLCGRRVC





330
RCLCRRRFC





331
RCLCRRRVC





332
RCLCRLRIC





333
RCICGLRVC





334
RCICGLRFC





335
RCICGRRFC





336
RCICVRRVC





337
RCICRLRIC





338
RCICTLRIC





339
RCICTRRFC





340
RCICTRRVC





341
RCICRRRFC





342
RCICRRRVC





343
RCLCGRRFC





344
RCLCVRRIC





345
RCLCTRRIC





346
RCICGRRVC





347
RCICGLRIC





348
RCICVRRIC





349
RCICTRRIC





350
RCICRRRIC





351
RCLCGRRIC





352
VTPAMRTFALLTAMLLLVALHAQAEARQARADEAAAQQQPGADDQGMAHS



FTRPENAALPLSESARGLRCICRRGVCQLLRRLGSCAFRGLCRICCRASRIKKN



TLRSYFESXKKFLLLLYLVLNFLFSSQINTFSQDFCL





353
VTPAMRTFALLTAMLLLVALHAQAEARQARADEAAAQQQPGADDQGMAHS



FTRPENAALPLSESARGLRCLCRRGVCQLLRRLGSCAFRGLCRICCRASRIKKN



TLRSYFESXKKFLLLLYLVLNFLFSSQINTFSQDFCL





354
VTPAMRTFALLTAMLLLVALAQAEPLQARADEAAAQEQPGADDQEMAHAFT



WDESAALPLSDSARGLRCIGGRGICGLLQRRVGSCAFRGTLHRICCRACRIKK



NKLRIYSESKKFLLLLYLVLHFLFSSKINTSLQDFSL





355
VTPAMRTFALLTAMLLLVALAQAEPLQARADEAAAQEQPGADDQEMAHAFT



WDESAALPLSDSARGLRCIGGRGICGLLQRRFGSCAFRGTLHRICCRACRIKKN



KLRIYSESKKFLLLLYLVLHFLFSSKINTLLQDFSL





356
VTPAMRTFALLTAMLLLVDLAQAEPLQARADEAAAQEQPGADDQEMAHAFT



WDESAALPLSDSARGLRCICGRGICRLLRRFGSCAFRGTLHRICCRACRIKKNK



LRIYFETKKFLLLLYLVLHFLFSSKINTLLQDFCL





357
VTPAMRTFTVLAAMLLVVALQAQAEPLRARADETAAQEQPGADDQEMAHAF



TWDESAALPLSDSARGLRCICRRGVCRLLRHFGSCAFRGTLHRICCRACRIKK



NKLRIYFESKKFLFLLYLALHFLFSSKINTLLQDFCL





358
VTPAMRTFTVLAAMLLVVALQAQAEPLRARADETAAQEQPGADDQEMAHAF



TWDESAALPLSDSARGLRCICRRGVCRFLRHLGSCAFRGTLHRICCRACRIKK



NKLRIYFESKKFVFLLYLALHFLFSSKINTLLQDFCL





359
VTPAMRTFALLAAMLLLVALAEAEPLQARADETAAQEQPGADDQEMAHAFT



WDESATLPLSDSARGLRCICRRGVCRFLRHLGSCAFRGTLHRICCRACRIKKN



KLRIYFESKKFVFLLYLALHFLFSSKINTLLQDFCL





360
VTPAMRTFALLTAMLLLVALAQAEPLQARADEAAAQEQPGADDQEMAHAFT



WHESAALPLSDSARGLRCICGRGICRLLRRFGSCAFRGTLHRICCRACRIKKHK



LRIYFESKKFLLLLYLVLHFLFSSKINTLLQDFSL





361
RCLCVLGIC





362
RCLCVLGVC





363
RCLCTLGIC





364
RCLCTLGVC





365
RCLCGLGIC





366
RCLCGLGVC





367
RCICVLGFC





368
RCICVLGVC





369
RCICTLGFC





370
RCICTLGVC





371
RCICRLGFC





372
RCICRLGVC





373
RCICGRGIC





374
RCLCVRGVC





375
RCLCTRGFC





376
RCLCTRGVC





377
RCLCRRGFC





378
RCLCRRGVC





379
RCLCRLGIC





380
RCICGLGVC





381
RCICGLGFC





382
RCICGRGFC





383
RCICVRGVC





384
RCICRLGIC





385
RCICTLGIC





386
RCICTRGFC





387
RCICTRGVC





388
RCICRRGFC





389
RCICRRGVC





390
RCLCGRGFC





391
RCLCGRGVC





392
RCLCVRGIC





393
RCLCTRGIC





394
RCICGRGVC





395
RCICGLGIC





396
RCICVRGIC





397
RCICTRGIC





398
RCICRRGIC





399
RCLCGRGIC





400
MRTFALLTAMLLLVALHAQAEARQARADEAAAQQQPGADDQGMAHSFTRP



ENAALPLSESARGLRCLCRRGVCQLL





401
MRTFALLTAMLLLVALHAQAEARQARADEAAAQQQPGTDDQGMAHSFTWP



ENAALPLSESAKGLRCICTRGFCRLL





402
MRIIALLAAILLVALQVRAGPLQARGDEAPGQEQRGPEDQDISISFAWDKSSAL



QVSGSTRGMVCSCRLVFCRRTELRVGNCLIGGVSFTYCCTRVD





403
AQAEPLQARADEAAAQEQPGADDQEMAHAFTWHESAALPLSDSARGLRCIC



GRGICRLL





404
RGCICRCIGRGCICRCIG





405
GICICICGRGICYCICGR





406
GICICICGYGICRCICGR





407
GICYCICGRGICRCICGR





408
GICRCICGRGYCRCICGR





409
GYCRCICGRGICRCICGR





410
GICRCICGRGICRCYCGR





411
GICRCYCGRGICRCICGR





412
GICRCICGKGICRCICGR





413
GICRCICGRGICRCICGR





414
VPKCCKPV





415
CKPV





416
SYSMEHFRWGKPV





417
HFRWGKPV





418
MEHFRWG





419
MAKSYGAIFLLTLIVLFMLQTMYMASSGSNVKWRQKRVGPGSLKRTQCPSEC



DRRCKKTQYHKACITFCNKCCRKCLCVPPGYYGNKQVCSCYNNWKTQEGGP



KCP





420
CDGKCKVRCSKASRHDDCLKYCGVCCASCNCVPSGTAGNKDECPCYRDMTT



GHGARKRP





421
ADVENSQKKNGYAKKIDCGSACVARCRLSRRPRLCHRACGTCCYRCNCVPPG



TYGNYDKCQCYASLTTHGGRRKCP





422
MVRCSLSSRPNLCHRACGTCCARCNCVAPGTSGNYDKCPCYGSLTTHGGRRK



EV





423
QSKDGPALEKWCGQKCEGRCKEAGMKDRCLKYCGICCKDCQCVPSGTYGNK



HECACYRDKLSSKGTPKCP





424
EQKQGQYGEGSLRPSECGQRCSYRCSATSHKKPCMFFCQKCCAKCLCVPPGT



FGNKQVCPCYNNWKTQQGGPKCP





425
CGGKCNVRCSKAGQHEECLKYCNICCQKCNCVPSGTFGHKDECPCYRDMKN



SKGGSKCP





426
YEFREIKFFFLCVYVQGDELESQAQAPAIHKNGGEGSLKPEECPKACEYRCSAT



SHRKPCLFFCNKCCNKCLCVPSGTYGHKEECPCYNNWTTKEGGPKCP





427
LVTSASKGSSFPKKIDCGGACAARCQLSSRPHLCKRACGTCCARSRCVPPGTA



GNQEMCPCYASLTTHGGKRKCP





428
MMISLLVFNPVEADGVVVNYGQHASLLAKIDCGGACKARCRLSSRPHLCKRA



CGTCCQRCSCVPPGTAGNYDVCPCYATLTTHGGKRKCP





429
LVTSAGKGNSSPKKIDCGGACAARCQLSSRPHLCKRACGTCCARCACVPPGT



AGNQEMCPKCYASLTTHGGKRKCP





430
GSLHPQDCQPKCTYRCSKTSFKKPCMFFCQKCCAKCLCVPAGTYGNKQTCPC



YNNWKTKEGGPKCP





431
ADVESSQKKNGYAKKIDCGSACVARCRLSRRPRLCHRACGTCCYRCNCVPPG



TYGNYDKCQCYASLTTHGGRRKCP





432
YELHVHAADGAKVGEGVVKIDCGGRCKDRCSKSSRTKLCLRACNSCCSRCNC



VPPGTSGNTHLCPCYASITTHGGRLKCP





433
AAEDSQVGEGVVKIDCGGRCKGRCSKSSRPNLCLRACNSCCYRCNCVPPGTA



GNHHLCPCYASITTRGGRLKCP





434
GRLHPQDCQPKCTYRCSKTSYKKPCMFFCQKCCAKCLCVPAGTYGNKQSCPC



YNNWKTKRGGPKCP





435
SVSNLVQAARGGGKLKPQQCNSKCSYRCSATSHKKPCMFFCLKCCKKCLCVP



PGTFGNKQTCPCYNNWKTKEGRPKCP





436
IFLLTLIVLFMLQTMVMASSGSNVKWRQKRYGPGSLKRTQCPSECDRRCKKT



QYHKACITFCNKCCRKCLCVPPGYYGNKQVCSCYNNWKTQEGGPKCP





437
IFLLTLIVLFMLQTMVMASSGSNVKWSQKRYGPGSLKRTQCPSECDRRCKKT



QYHKACITFCNKCCRKCLCVPPGYYGNKQVCSCYNNWKTQEGGPKCP





438
LRPTDCKPRCTYRCSATSHKKPCMFFCQKCCATCLCVPKGVYGNKQSCPCYN



NWKTQEGKPKCP





439
KSYQCGGQCTRRCSNTKYHKPCMFFCQKCCAKCLCVPPGTYGNKQVCPCYN



NWKTQQGGPKCP





440
SKINCGAACKARCRLSSRPNLCHRACGTCCARCRCVPPGTSGNQKVCPCYYN



MTTHGGRRKCP





441
MKLFLLTLLLVTLVITPSLIQTTMAGSNFCDSKCKLRCSKAGLADRCLKYCGV



CCEECKCVPSGTYGNKHECPCYRDKKNSKGKSKCP





442
HEVQHIDCNAACAARCRLASRQRMCHRACGTCCRRCNCVPPGTSGNQEVCP



CYASLATHGGRRKCP





443
MAARSYSPIMVALSLLLLVTFSNVAEAYTRSGTLRPSDCKPKCTYRCSATSHK



KPCMFFCQKCCAKCLCVPPGTYGNKQICPCYNSWKTKEGGPKCP





444
MAMAKVFCVLLLALLGISMITTQVMATDSAYHLDGRNYGPGSLKSSQCPSEC



TRRCSQTQYHKPCMVFCKQCCKRCLCVPPGYYGNKSVCPCYNNWKTKRGGP



KCP





445
MAVANKLLSVLIIALIAISMLQTVVMASHGHGGHHYNDKKKYGPGSLKSFQC



PSQCSRRCGKTQYHKPCMFFCQKCCRKCLCVPPGYYGNKAVCPCYNNWKTK



EGGPKCP





446
MAKFFAAMILALIAISMLQTVVMAANEQGGHLYDNKSKYGSGSVKRYQCPS



QCSRRCSQTQYHKPCMFFCQKCCRKCLCVPPGYYGNKAVCPCYNNWKTKEG



GPKCP





447
MAKFFAAMILALFAISILQTVVMAANEQGGHLYDNKSKYGSGSVKSYQCPSQ



CSRRCSQTQYHKPCMFFCQKCCRTCLCVPPGYYGNKAVCPCYNNWKTKEGG



PKCP





448
MASNSILLLCIFLVVATKVFSYDEDLKTVVPAPAPPVKAPTLAPPVKSPSYPPG



PVTTPTVPTPTVKVPPPPQSPVVKPPTPTVPPPTVKVPPPPQSPVVKPPTPTPTSP



VVYPPPVAPSPPAPVVKSNKDCIPLCDYRCSLHSRKKLCMRACITCCDRCKCV



PPGTYGNREKCGKCYTDMLTHGNKFKCP





449
MEKKRKTLLLLLLMAATLFCMPIVSYAVSSVNIQGHLTHSELVKGPNRRLLPF



VDCGARCRVRCSLHSRPKICSRACGTCCFRCRCVPPGTYGNREMCGKCYTDM



ITHGNKPKCP





450
MALSKLIIASLLASLLLLHFVDADQSAHAQTQGSLLQQIDCNGACAARCRLSS



RPRLCQRACGTCCRRCNCVPPGTAGNQEVCPCYASLTTHGGKRKCP





451
MALRVLLVLGMLLMLCLVKVSSDPKIEEEILEAEEELQFPDNEPLIVRDANRRL



MQDMDCGGLCKTRCSAHSRPNLCTRACGTCCVRCKCVPPGTSGNRELCGTC



YTDMTTHGNKTKCP





452
MAPRVFLVLGMLLMVCLVKVSSDPKREEEILEEELHFPDNEPLIVRDGNRRLM



QDIDCGGLCKTRCSAHSRPNLCTRACGTCCVRCKCVPPGTSGNRELCGTCYTD



MTTHGNKTKCP





453
MMGILLLVCLAKVSSDVNMQKEEDEELRFPNHPLIVRDGNRRLMQDIDCGGL



CKTRCSAHSRPNVCNRACGTCCVRCKCVPPGTSGNRELCGTCYTDMITHGNK



TKCP





454
MKLVFATLLLCSLLLSSSFLEPVIAYEDSSYCSNKCSDRCSSAGVKDRCLRYCG



ICCAECKCVPSGTYGNKHQCPCYRDKLNKKGKPKCP





455
MKLEFANVLLLCLVLSSSFLEISMAGSPFCDSKCAQRCAKAGVQDRCLRFCGI



CCEKCNCVPSGTYGNKDECPCYRDMKNSKGKDKCP





456
MAPGKLAVFALLASLLLLNTIKAADYPPAPPLGPPPHKIVDPGKDCVGACDAR



CSEHSHKKRCSRSCLTCCSACRCVPAGTAGNRETCGRCYTDWVSHNNMTKCP





457
MLLLALAAHHQAASDPPATHGGMRASGTRSLLQQQPPPPRLDCPKVCAGRCA



NNWRKEMCNDKCNVCCQRCNCVPPGTGQDTRHICPCYATMTNPHNGKLKCP





458
MVTKVICFLVLASVLLAVAFPVSALRQQVKKGGGGEGGGGGSVSGSGGGNL



NPWECSPKCGSRCSKTQYRKACLTLCNKCCAKCLCVPPGFYGNKGACPCYNN



WKTREGGPKCP





459
MSKPSRCRAVQTQVALLLLLLVAASLLQAGDAASGFCAGKCAVRCGRSRAK



RGACMKYCGLCCXECACVPTGRSGSRDECPCYRDMLTAGPRKRPKCP





460
MKPLPVTLALLALFLVASYQDLTVAADADADAAGAGDVGAVPVPDSVCEGK



CKNRCSQKVAGRCMGLCMMCCGKCAGCVPSGPLAPKDECPCYRDMKSPKS



GRPKCP





461
MKKLRTTTATTTLALILLLVLIAATSLRVAMAGSAFCDSKCGVRCSKAGRHD



DCLKYCGICCAECNCVPSGTAGNKDECPCYRDKTTGHGARTRPKCP





462
MKKLRTTTLALLLLLVFLAASSLRAAMAGSAFCDGKCGVRCSKASRHDDCLK



YCGICCAECNCVPSGTAGNKDECPCYRDKTTGHGARKRPKCP





463
MGGGNGGAGGGGKLKPWECSSKCSSRCSGTQYKKACLTYCNKCCATCLCVP



PGTYGNKGACPCYNNWKTKEGGPKCP





464
MESKSPWSLRLLICCAAMVAIALLPQQGGQAACFVPTPGPAPAPPGSSATNTN



ASSAAPRPAKPSAFPPPMYGGVTPGTGSLQPHECGGRCAERCSATAYQKPCLF



FCRKCCAACLCVPPGTYGNKNTCPCYNNWKTKRGMYGGVTPGTGSLQPHEC



GGRCAERCSATAYQKPCLFFCRKCCAACLCVPPGTYGNKNTCPCYNNWKTK



RGGPKCP





465
MAKASSRLLFSLSLVVLLLLVETTTSPHGQADAIDCGASCSYRCSKSGRPKMC



LRACGTCCQRCGCVPPGTSGNEDVCPCYANMKTHDGQHKCP





466
MKAIPVALLLLVLVAAASSFKHLAEAADGGAVPDGVCDGKCRSRCSLKKAG



RCMGLCMMCCGKCQGCVPSGPYASKDECPCYRDMKSPKNQRPKCP





467
MMTTMKKKKQQQQLLLLSLMFLVAVTAAAVAADPHPQQVQVQQQQQAQM



RINRATRSLLPQPPPKLDCPSTCSVRCGNNWKNQMCNKMCNVCCNKCSCVPP



GTGQDTRHLCPCYDTMLNPHTGKLKCP





468
MAVAKPPLQTAAVLLLLLLVVAAASWLQTVDAASGFCSSKCSVRCGRAASA



RARGACMRSCGLCCEECNCVPTRPPRDVNECPCYRDMLTAGPRKRPKCP





469
MAPSKLAVVVALVASLLLLTTSNTKLGLFVLGQAAPGAYPPRAPPPHQIVDLA



KDCGGACDVRCGAHSRKNICTRACLKCCGVCRCVPAGTAGNQQTCGKCYTD



WTTHGNKTKCP





470
MKLQATARVAGLLFLVLLLALPSLRVSMAGSGFCDGKCAVRCSKASRHDDCL



KYCGICCATCNCVPSGTAGNKDECPCYRDMTTGHGNRTRPKCP





471
MVTKVICFLVLASVLLAVAFPVSALRQQVKKGGGGEGGGGGSVSGSGGGNL



NPWECSPKCGSRCSKTQYRKACLTLCNKCCAKCLCVPPGFYGNKGACPCYNN



WKTKEGGPKCP





472
MNNLHRELAPIASAAWEQIEEEVARTFKRSVAGRRVVDVEGPKGPALSAVGT



GHLRDVDAPREQVSARLREVRAIVELTVPFELSRDAIDSVERGARDADWQPA



KDAAQRLAFAEDHAIFDGYAAAGIIGIREGSSNRRLTLPDDVGAYPDAISDALE



ALRLAGVDGPYSVLLGADAYTALSEARDQGYPVIDHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKVVRLYLRETFTFLML





473
MNNLHRELAPISSAAWEQIEEEVARTFKRSVAGRRVVDVEGPAGPELSAVGT



GHLLDVAAPRELVNARLREVRTIVELTVPFELSRDAIDSVERGARDADWQPAK



EAAQRLAFAEDNAIFDGYPAAGIVGIREGTSNRRLTLPADVGAYPDAISDALE



ALRLAGVDGPYSVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKGVRLYLRETFTFLML





474
KFAKKAAKKFAKKAAK





475
KFAKKFAKKAAKKAAK





476
KFAKKFAKKFAKKAAK





477
FKLRAKIKVRLRAKIKL





478
FAKKFAKKFKKFAKKFAKFAFAF





479
KGKKGKKGKKGKKGKKGKKGK





480
KFKKFKKFKKFK





481
KFKKFKKFK





482
KFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFA



KKFAKKFAKKFAKKFAKKFAKKFAKKFAK





483
LKLKLKLKLKLKLK





484
KFAKKFAKKFAK





485
KFAKKFAK





486
KFAK





487
KTKKTKKTKKTKKTKKTKKTK





488
KGKKGKKGKKGKKGKKGKKGKKGKKGKKGKKGKKGKKGKKGKKGK





489
KGKKGKKGKKGKKGKKGKKGKKGKKGKKGKKGK





490
LRLRLRLRLRLRLRLRLRLRLR





491
LRLRLRLRLRLRLRLRLR





492
LRLRLRLRLRLRLR





493
LKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLK





494
LKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLKLK





495
LKLKLKLKLKLKLKLKLKLKLKLK





496
LKLKLKLKLKLKLKLKLKLKLK





497
LKLKLKLKLKLKLKLKLKLK





498
LKLKLKLKLKLKLKLKLK





499
LKLKLKLKLKLKLKLK





500
LKLKLKLKLK





501
LKLK





502
FKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAF



KAFKAFKAFKA





503
FKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKAFKA





504
FKAFKAFKAFKAFKAFKAFKAFKAFKAFKA





505
FKAFKAFKAFKAFKAFKAFKAFKAFKA





506
FKAFKAFKAFKAFKAFKAFKAFKA





507
FKAFKAFKAFKAFKAFKAFKA





508
FKAFKAFKAFKAFKAFKA





509
FKAFKAFKAFKA





510
FKAFKA





511
KFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKK



FKKFKKFKKFK





512
KFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFK





513
KFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFKKFK





514
KFKKFKKFKKFKKFKKFKKFKKFKKFKKFK





515
KFKKFKKFKKFKKFKKFKKFKKFKKFK





516
KFKKFKKFKKFKKFKKFKKFKKFK





517
KFKKFKKFKKFKKFKKFKKFK





518
KFKKFKKFKKFKKFKKFK





519
KFKKFKKFKKFKKFK





520
KKAKKKAKKKAKKKAKKKAKKKAKKKAK





521
KAAKKAAKKAAKKAAKKAAKKAAKKAAK





522
KFAKKFAKKFAKKFAKKFAKKFAKKFAK





523
KFFKKFFKKFFKKFFKKFFKKFFKKFFK





524
KFAFKFAFKFAFKFAFKFAFKFAFKFAF





525
LKKLLKKLLKKLLKKLLKKLLKKLLKKLLKKL





526
LKKLLKKLLKKLLKKLLKKLLKKLLKKL





527
LKKLLKKLLKKLLKKLLKKLLKKL





528
LKKLLKKLLKKLLKKLLKKL





529
KKFAKKFAKKFAKKFAKKFAKKFA





530
AKKFAKKFAKKFAKKFAKKFAKKF





531
FAKKFAKKFAKKFAKKFAKKFAKK





532
RFARRFARRFARRFARRFARRFARRFARRFAR





533
RFARRFARRFARRFARRFARRFARRFAR





534
RFARRFARRFARRFARRFARRFAR





535
KFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFA



KKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAK





536
KFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFA



KKFAKKFAKKFAKKFAK





537
KFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAK





538
KFAKKFAKKFAKKFAKKFAKKFAKKFAKKFAK





539
KFAKKFAKKFAKKFAKKFAKKFAK





540
KFAKKFAKKFAKKFAKKFAK





541
KFAKKFAKKFAKKFAK





542
RIIRKIIHII





543
RIIRKIIHIIK





544
RRIIRKIIHII





545
NIRRIIRKIIHIIKKY





546
NLRRIIRKIIHIIKKY





547
RGLRALGRKIAHGVKAYG





548
KNLRRIIRKIIHIIKKYGPTILRIIRIIG





549
RGLRRLGRKIAHGVKKYGPTVLRIIRIA





550
KIKEKLKKIGQKIQGLL





551
KIKEKLKKIGQKIQG





552
RKFRNKIKEKLKKIG





553
LRKFRNKIKEKLKKIGQKIQG





554
LRKFRNKIKEKLKKIGQKI





555
RKRLRKFRNKIKEKLKKIGQKI





556
KRLRKFRNKIKEKLKKIG





557
GLRKRLRKFRNKIKEKLKKIG





558
GLRKRLRKFRNKIKEKLKKIGQKIQGLLPKLAPRTDY





559
RRIIRKIIHIIK





560
RRIIRKIIHIIKK





561
LRRIIRKIIHIIK





562
IRRIIRKIIHIIKK





563
LRRIIRKIIHIIKK





564
KNLRRIIRKIIHIIKKYG





565
KNIRRIIRKIIHIIKKYG





566
RGLRRLGRKIAHGVKKYG





567
LGRKIAHGVKKYGPTVLRII





568
KIAHGVKKYGPTVLRIIRIAG





569
RGLRRLGRKIAHGVKKYGPTVLRIIRIAG





570
HPHVCTSYYCSKFCGTAGCTRYGCRNLHRGKLCFCLHCSR





571
HSHACTSYWCGKFCGTASCTHYLCRVLHPGKMCACVHCSR





572
HXHXCTSYXCXKFCGTAXCTXYXCRXLHXGKXCXCXHCSR





573
MKATMLLAVVVAVFVAGTEAHPHVCTSYYCSKFCGTAGCTRYGCRNLHRGK



LCFCLHCSRVKFPFGATQDAKSMNELEYTPIMKSMENLDNGMDML





574
MKATILLAVLVAVFVAGTEAHSHACTSYWCGKFCGTASCTHYLCRVLHPGK



MCACVHCSRVNNPFRVNQVAKSINDLDYTPIMKSMENLDNGMDML





575
KWKLFKKIGIGAVLKVLTTGLPALKKTK





576
KWKLFKKIGIGAVLKVLTTGLPALIS





577
KKWWRRXXXGLKTAGPAIQSVLNK





578
KWKSFIKK





579
KKWWKX





580
KKWWRRX





581
KKWRKSFFKQVGSFDNSV





582
WKVFKSFIKKASSFAQSVLD





583
KKSFFKKLTSVASSVLS





584
KKWWKFIKKAVNSGTTGLQTLAS





585
KKWWKAKKFANSGPNALQTLAQ





586
KKWWKAQKAVNSGPNALQTLAQ





587
KKWWRRALQGLKTAGPAIQSVLNK





588
KKWWRRVLSGLKTAGPAIQSVLNK





589
KKWWRRALQALKNGPALSNV





590
KKWWRRVLKGLSSGPALSNV





591
KKWWRRVLSGLKTGPALSNV





592
KWKKFIKELQKVLKPGGLLSNIVTSL





593
KKKSFIKLLTSAKVSVLTTAKPLISS





594
KWKSFIKKLTSVLKKVVTTAKPLISS





595
KWKLFKKKGTGAVLTVLTTGLPALIS





596
KWKSFIKNLTKVLKKVVTTALPALIS





597
KWKSFIKKLTSVLKKVVTTALPALIS





598
KWKKFIKELQKVLAPGGLLSNIVTSL





599
KWKEFIKKLTTAVKKVLTTGLPALIS





600
KWKSFIKNLEKVLKKGPILANLVSIV





601
KWKSFIKNLEKVLKPGGLLSNIVTSL





602
KWKKFIKNLTKGGSKILTTGLPALIS





603
KWKSFIKNLTKGGSKILTTGLPALIS





604
KWKSFIKKLTSAAKKVVTTAKPLISS





605
KWKSFIKKLTTAVKKVLTTGLPALIS





606
RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWRVV





607
VRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR





608
RRWVRRVRRVWRRVVRVVRRWVRR





609
RVVRVVRRWVRR





610
RVVRVVRRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR





611
RRVVRRVRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR





612
VRRVVRRVVRVVRRVVRRVRRVVRRVVRVVRRVVRR





613
RRVVRRVRRVVRRVVRVVRRVVRR





614
RVVRVVRRVVRR





615
RWIRVVQRWCRAIRHIWRRIRQGLRRWLRVV





616
RVIRVVQRACRAIRHIVRRIRQGLRRILRVV





617
RVIRVVQRACRAIRHIVRRIRQGLRRIL





618
MQYNRR





619
FVNVVPTFGKKKGPNANS





620
TGRAKRR





621
AKVAKQEKKKKKTGRAKRRA





622
KVAKQEKKKKKTGRAKRR





623
KVAKQEKKKKKT





624
TGRAKRRMQYNRR





625
KVHGSLARAGKVRGQTPK





626
KVHGSLARAGKVRGQTPKVAKQEKKKKKTGRAKRRMQYNRRFVNVVPTFG



KKKGPNANS





627
MKLNTTTTLALLLLLLLASSSLQVSMAGSDFCDGKCKVRCSKASRHDDCLKY



CGVCCASCNCVPSGTAGNKDECPCYRDMTTGHGARKRPKCP





628
QSKDGPALEKWCGQKCEGRCKEAGMKDRCLKYCGICCKDCQCVPSGTYGNK



HECACYRDKLSSKGTPKCP





629
SVSNLVQAARGGGKLKPQQCNSKCSYRCSATSHKKPCMFFCLKCCKKCLCVP



PGTFGNKQTCPCYNNWKTKEGRPKCP





630
MAARSYSPIMVALSLLLLVTFSNVAEAYTRSGTLRPSDCKPKCTYRCSATSHK



KPCMFFCQKCCAKCLCVPPGTYGNKQICPCYNSWKTKEGGPKCP





631
MAKEFFAAMILALIAISMLQTVVMAANEQGGHLYDNKSKYGSGSVKRYQCPS



QCSRRCSQTQYHKPCMFFCQKCCRKCLCVPPGYYGNKAVCPCYNNWKTKEG



GPKCP





632
MAKEFFAAMILALFAISLILQTVVMAANEQGGHLYDNKSKYGSGSVKSYQCPSQ



CSRRCSQTQYHKPCMFFCQKCCRTCLCVPPGYYGNKAVCPCYNNWKTKEGG



PKCP





633
MASNSILLLCIFLVVATKVFSYDEDLKTVVPAPAPPVKAPTLAPPVKSPSYPPG



PVTTPTVPTPTVKVPPPPQSPVVKPPTPTVPPPTVKVPPPPQSPVVKPPTPTPTSP



VVYPPPVAPSPPAPVVKSNKDCIPLCDYRCSLHSRKKLCMRACITCCDRCKCV



PPGTYGNREKCGKCYTDMLTHGNKFKCP





634
MEKKRKTLLLLLLMAATLFCMPIVSYAVSSVNIQGHLTHSELVKGPNRRLLPF



VDCGARCRVRCSLHSRPKICSRACGTCCFRCRCVPPGTYGNREMCGKCYTDM



ITHGNKPKCP





635
MALSKLIIASLLASLLLLHFVDADQSAHAQTQGSLLQQIDCNGACAARCRLSS



RPRLCQRACGTCCRRCNCVPPGTAGNQEVCPCYASLTTHGGKRKCP





636
MALRVLLVLGMLLMLCLVKVSSDPKIEEEILEAEEELQFPDNEPLIVRDANRRL



MQDMDCGGLCKTRCSAHSRPNLCTRACGTCCVRCKCVPPGTSGNRELCGTC



YTDMTTHGNKTKCP





637
MAPRVFLVLGMLLMVCLVKVSSDPKREEEILEEELHFPDNEPLIVRDGNRRLM



QDIDCGGLCKTRCSAHSRPNLCTRACGTCCVRCKCVPPGTSGNRELCGTCYTD



MTTHGNKTKCP





638
MMGILLLVCLAKVSSDVNMQKEEDEELRFPNHPLIVRDGNRRLMQDIDCGGL



CKTRCSAHSRPNVCNRACGTCCVRCKCVPPGTSGNRELCGTCYTDMITHGNK



TKCP





639
MAISKSTVVVVILCFILIQELGIYGEDPHMDAAKKIDCGGKCNSRCSKARRQK



MCIRACNSCCKKCRCVPPGTSGNRDLCPCYARLTTHGGKLKCP





640
MKLVFGTLLLCSLLLSFSFLEPVIAYEDSSYCSNKCADRCSSAGVKDRCVKYC



GICCAECKCVPSGTYGNKHECPCYRDKLNKKGKPKCP





641
MKLVFATLLLCSLLLSSSFLEPVIAYEDSSYCSNKCSDRCSSAGVKDRCLRYCG



ICCAECKCVPSGTYGNKHQCPCYRDKLNKKGKPKCP





642
MKLEFANVLLLCLVLSSSFLEISMAGSPFCDSKCAQRCAKAGVQDRCLRFCGI



CCEKCNCVPSGTYGNKDECPCYRDMKNSKGKDKCP





643
MKVAFAAVLLICLVLSSSLFEVSMAGSAFCSSKCSKRCSRAGMKDRCMKFCGI



CCSKCNCVPSGTYGNKHECPCYRDMKNSKGKAKCP





644
MKVAFVAVLLICLVLSSSLFEVSMAGSAFCSSKCAKRCSRAGMKDRCTRFCGI



CCSKCRCVPSGTYGNKHECPCYRDMKNSKGKPKCP





645
LRPWECSPKCAGRCSNTQYKKACLTFCNKCCAKCLCVPPGTYGNKGACPCY



NNWKTKEGGPKCP





646
KDCVGACDARCSEHSHKKRCSRSCLTCCSACRCVPAGTAGNRETCGRCYTD



WVSHNNMTKCP





647
MLLLALAAHHQAASDPPATHGGMRASGTRSLLQQQPPPPRLDCPKVCAGRCA



NNWRKEMCNDKCNVCCQRCNCVPPGTGQDTRHICPCYATMTNPHNGKLKCP





648
MVTKVICFLVLASVLLAVAFPVSALRQQVKKGGGGEGGGGGSVSGSGGGNL



NPWECSPKCGSRCSKTQYRKACLTLCNKCCAKCLCVPPGFYGNKGACPCYNN



WKTREGGPKCP





649
MSKPSRCRAVQTQVALLLLLLVAASLLQAGDAASGFCAGKCAVRCGRSRAK



RGACMKYCGLCCXECACVPTGRSGSRDECPCYRDMLTAGPRKRPKCP





650
MKPLPVTLALLALFLVASYQDLTVAADADADAAGAGDVGAVPVPDSVCEGK



CKNRCSQKVAGRCMGLCMMCCGKCAGCVPSGPLAPKDECPCYRDMKSPKS



GRPKCP





651
MKKLRTTTATTTLALILLLVLIAATSLRVAMAGSAFCDSKCGVRCSKAGRHD



DCLKYCGICCAECNCVPSGTAGNKDECPCYRDKTTGHGARTRPKCP





652
MKKLRTTTLALLLLLVFLAASSLRAAMAGSAFCDGKCGVRCSKASRHDDCLK



YCGICCAECNCVPSGTAGNKDECPCYRDKTTGHGARKRPKCP





653
MESKSPWSLRLLICCAAMVAIALLPQQGGQAACFVPTPGPAPAPPGSSATNTN



ASSAAPRPAKPSAFPPPMYGGVTPGTGSLQPHECGGRCAERCSATAYQKPCLF



FCRKCCAACLCVPPGTYGNKNTCPCYNNWKTKRGGPKCP





654
MAKASSRLLFSLSLVVLLLLVETTTSPHGQADAIDCGASCSYRCSKSGRPKMC



LRACGTCCQRCGCVPPGTSGNEDVCPCYANMKTHDGQHKCP





655
MKAIPVALLLLVLVAAASSFKHLAEAADGGAVPDGVCDGKCRSRCSLKKAG



RCMGLCMMCCGKCQGCVPSGPYASKDECPCYRDMKSPKNQRPKCP





656
MMTTMKKKKQQQQLLLLSLMFLVAVTAAAVAADPHPQQVQVQQQQQAQM



RINRATRSLLPQPPPKLDCPSTCSVRCGNNWKNQMCNKMCNVCCNKCSCVPP



GTGQDTRHLCPCYDTMLNPHTGKLKCP





657
MAVAKPPLQTAAVLLLLLLVVAAASWLQTVDAASGFCSSKCSVRCGRAASA



RARGACMRSCGLCCEECNCVPTRPPRDVNECPCYRDMLTAGPRKRPKCP





658
MAPSKLAVVVALVASLLLLTTSNTKLGLFVLGQAAPGAYPPRAPPPHQIVDLA



KDCGGACDVRCGAHSRKNICTRACLKCCGVCRCVPAGTAGNQQTCGKCYTD



WTTHGNKTKCP





659
MKLQATARVAGLLFLVLLLALPSLRVSMAGSGFCDGKCAVRCSKASRHDDCL



KYCGICCATCNCVPSGTAGNKDECPCYRDMTTGHGNRTRPKCP





660
MVTKVICFLVLASVLLAVAFPVSALRQQVKKGGGGEGGGGGSVSGSGGGNL



NPWECSPKCGSRCSKTQYRKACLTLCNKCCAKCLCVPPGFYGNKGACPCYNN



WKTKEGGPKCP





661
KWKGIGAVLKVLTTGX





662
KWKLFKKIGIGAVLKVLTTGLPALIX





663
RLCRVVIRVCR





664
CYCRIPACIAGERRYGTCIYQGRLWAFCC





665
MPRWRLFRRIDRVGKQIKQGILRAGPAIALVGDARAVG





666
KWKVFKKIEKMGRNIRNGIVKAGPAIAVLGEAKALG





667
KWKLFKKIEKVGQNIRDGIIKAGPAVAVVGQATQIAK





668
GIGKFLKKAKKFGKAFVKILKK





669
GIGKFLKKAKKFGKAFVKILKX





670
MNLAKGKEESLDSDLYAELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIA



TLKDGRKICLDPDAPRIKKIVQKKLAGDESAD





671
MGHHHHHHHHHHSSGHIEGRHMYAELRCMCIKTTSGIHPKNIQSLEVIGKGTH



CNQVEVIATLKDGRKICLDPDAPRIKKIVQKKLAGDESAI





672
MGHHHHHHHHHHSSGHIEGRHMYLRCMCIKTTSGIHPKNIQSLEVIGKGTHC



NQVEVIATLKDGRKICLDPDAPRIKKIVQKKLAGDESAD





673
MNLAKGKEESLDSDLYAELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIA



TLKDGRKICLDPDAPRIKKIVQKKLAGDES





674
MAELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIATLKDGRKICLDPDAP



RIKKIVQKKLAGDES





675
AELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIATLKDGRKICLDPDAPRI



KKIVQKKLAGDESAD





676
LRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIATLKDGRKICLDPDAPRIKK



IVQKKLAGDESAD





677
NLAKGKEESLDSDLYAELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIAT



LKDGRKICLDPDAPRIKKIVQKKLAGDES





678
AGDES





679
YAELR





680
AELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIATLKDGRKICLDPDAPRI



KKIVQKKLAGDES





681
AELR





682
NLAKGKEESLDSDLYAELRCMCIKTTSGIHPKNIQSLEVIGKGTHCNQVEVIAT



LKDGRKICLDPDAPRIKKIVQKKLAGDESAD





683
RVIEVVQGACRAIRHIPRRIRQGLERIL





684
RVVRVVRRWVRRVRRVWRRVVRVVRRWVRRVRRVWRRVVRVVRRWVRR





685
WRWWKVVWRWVKW





686
WRWWKVWRWVKW





687
ILRWPWWPWRRK





688
RLARIVVIRVAR





689
GKPRPYSPIPTSPRPIRY





690
KWKLFIKKLTPAVKKVLLTGLPALIS





691
KWKSFIKKLTSAAKKVLTTGLPALIS





692
KWKLFKKIGIGAVLKVLTTGLPALKLTK





693
KKWWRRALQALKNGLPALIS





694
WRWWKVAWRWVKW





695
WRWWKPKWRWPKW





696
RRIWKPKWRLPKR





697
ILRWPWWPWRRA





698
ILRWPWWPWRAK





699
ILRWPWWPWARK





700
ILRWPWWPARRK





701
ILRWPWWAWRRK





702
ILRWPWAPWRRK





703
ILRWPAWPWRRK





704
ILRWAWWPWRRK





705
ILRAPWWPWRRK





706
ILAWPWWPWRRK





707
IARWPWWPWRRK





708
ALRWPWWPWRRK





709
RWWWPWRRK





710
WPWWPWRRK





711
LRWPWWPW





712
LRWWWPWRRK





713
LWPWWPWRRK





714
ILKKWPWWPWR








715
ILKKWPWWPWK





716
ILKKWPWWPWRR





717
ILKKWPWWPRRK





718
ILKKWPWWWRRK





719
ILKKWWWPWRRK





720
ILKKPWWPWRRK





721
IKKWPWWPWRRK





722
WVRLWWRRVW





723
RLWVWWVWRR





724
RLVVWVVWRR





725
RLFVWWVFRR





726
RLVVWWVVRR





727
RLWWVVWWRR





728
RLGGGWVWWVWRR





729
RLWVWWVWRRK





730
ILRWWVWWVWWRRK





731
ILRRWVWWVWRRK





732
KRRWVWWVWRLI





733
ILRWVWWVWRRK





734
ILKKWVWWPWRRK





735
ILKKWPWWVWRRK





736
ILKKWVWWVWRRK





737
ILKKWPWWPWRRK





738
CLRWPWWPWRRK





739
WRIWKPKWRLPKW





740
ILKKWPWWWRK





741
ILKKWWWPWRK





742
ILKKWPWWPWRRIM





743
ILKKWPWWPWRRKM





744
ILKKWPW





745
WWPWRRK





746
ILKKWPWWPWRRIMILKKAGS





747
ILKKWPWWPWRRMILKKAGS





748
ILKKWPWWPWRRKMILKKAGS





749
PWWPWRRK





750
LKKWPWWPWRRK





751
WWKKWPWWPWRRK





752
ILKKWPWWAWRRK





753
ILKKWAWWPWRRK





754
ILKWVWWVWRRK





755
KRKWPWWPWRLI





756
ILRWPWWPWRRKILMRWPWWPWRRKMAA





757
ILRWPWRRWPWRRK





758
ILRWPWWPWRRKDMILKKAGS





759
ILRWPWWPWRRKMILKKAGS





760
ILRWPWWPWRRKIMILKKAGS





761
ILKKWPWWPWKKK





762
ILRRWPWWPWRRR





763
ILWPWWPWRRK





764
KRRWPWWPWRLI





765
ILKWPWWPWRK





766
ILKKWPWWPWRK





767
ILKWPWWPWRRK





768
ILRRWPWWPWRK





769
ILRRWPWWPWRRK





770
WWRWPWWPWRRK





771
ILRWPWWPWWPWRRK





772
ILRYVYYVYRRK





773
ILKKFPFWPWRRK





774
ILKKFPWFPWRRK





775
ILKKYPWYPWRRK





776
ILKKWPWPWRRK





777
ILKKYPYYPYRRK





778
ILKKIPIIPIRRK





779
ILKKFPFLPFRRK





780
KRRWPWWPWKKLI





781
KKAAAKAAAAAKAAWAAKAAAKKKK





782
DPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCK





783
ALWKTMLKKLGTMALHAGKAALGAAADTISQTQ





784
SIGSAFKKAAHVGKHVGKAALGAAARRRK





785
ALWKTMLKKAAHVGKHVGKAALGAAARRRK





786
GWGSFFKKAAHVGKHVGKAALGAAARRRK





787
SIGSAFKKAAHVGKHVGKAALTHYL





788
ALWKTMLKKAAHVGKHVGKAALTHYL





789
KGWGSFFKKAAHVGKHVGKAALTHYL





790
KKWKKFIKKIGIGAVLTTPGAKK





791
KWKKFIKKIGIGAVLKVLTTGLPALKLTKK





792
KWKSFIKKLTSAAKKVTTAAKPLTK





793
KLWKLFKKIGIGAVLKVLKVLTTGLPALKLTLK





794
KWKFKKIGIGAVLKVLKVLTTGLPALKLTLK





795
KLFKKIGIGAVLKVLKVLTTGLPALKLTLK





796
KWKLFKKIGIGAVLKVLKVLTTGLPALKLTLK





797
KWKKFIKSLTKSAAKTVVKTAKKPLIV





798
KWKSFIKKLTKAAKKVVTTAKKPLIV





799
KWKSFIKKLTSAAKKVVTTAKPLALIS





800
HIFR





801
FFRHLFRGAKAIFRGARQGXRAHKVVSRYRNRDVPETDNNQEEP





802
FFHHIFRGIVHVGKTIHRLVTG





803
FIHHIFRGIVHAGRSIGRFLTG





804
RRWCFRVCYRGXFCYRKCR





805
RRWCXRVCYXGFCYRKCR





806
RXWCXXXCYRGFCXXXCR





807
RRWCFXVCXRGXCYXXCRX





808
XRWCFRVCYXGXCXXXCR





809
WCFXVCXRGXCRXKCRR





810
RRWCFRVCYRGRFCYRKCR





811
RRWCRRVCYAGFCYRKCR





812
RVWCRYRCYRGFCRRFCR





813
RVWCRRRCYRGFCRYFCR





814
RRWCFIVCRRGRCYVACRR





815
RRWCFIVCRRGACYRRCR





816
RRWCFRVCYRGFCRYFCR





817
RRWCFRVCYKGFCRYKCR





818
FRWCFRVCYKGRCRYKCR





819
WCFAVCYRGRCRRKCRR





820
WCFAVCRRGRCRYKCRR





821
ALYKKKIIKKLLES





822
YAERLCXCSIKAEV





823
ANLIATKKNGRKLCL





824
KFDKSKLKKTETQEKNPL





825
EGVNDNEEGFFSA





826
ADSGEGDFLAEGGGVRKLIK





827
ADSGEGDFLAEGGGVR





828
SWVQEYVYDLEL





829
EWVQKYVSDLELSAWKKILK





830
KWVREYINSLEMSKKGLAG





831
PRIKKIVQKKLAG





832
KWKWWWWWKWK





833
KGYFYFLFKFK





834
KFKHYFFWKYK





835
YAERLCTCSIKAEV





836
SAIHPSSILKLEVICIGVLQ





837
RFEKSKIK





838
ATKKNGRKLCLDLQAAL





839
ALYKRLFKKLKKF





840
GLYKRLFKKLLKS





841
ALYKKLFKKLLKR





842
KLYKKWKNKLKRSLKRLG





843
ALYKKWKNKLLKS





844
KLYKKWKKKLLKLK





845
ARYRKFRNKILRS





846
ARYRKFKNKILKS





847
KLYRKFKNKLLKLK





848
ARYKKFKKKLLKS





849
ALYKKFKKKLLKSLKRLG





850
SDDPKESEGDLHCVCVKTTSLVRPGHITNLELIKAGGHCPTANLIATKKNGRK



LCLDLQAALYKKKIIKKLLES





851
SDDPKESEGDLHCVCVKTTSLVRPRHITNLELIKAGGHCPTANLIATKKNGRK



LCLDLQAALYKKKIIKKLLES





852
RHFCGGALIHARYVMTAASS





853
RHYCGGALIHARFVMTAASS





854
RHFCGGALIHARFAMTAASS





855
RHFCGGALIHARFIMTAASS





856
RHFCGGALIHARFLMTAASS





857
RHFCAAALIHARFVMTAASS





858
RHFCGAALIHARFVMTAASS





859
RHFCAGALIHARFVMTAASS





860
RHFSGGALIHARYVMTAASC





861
RHYSGGALIHARFVMTAASC





862
RHFSGGALIHARFAMTAASC





863
RHFSGGALIHARFIMTAASC





864
RHFSGGALIHARFLMTAASC





865
RHFSAAALIHARFVMTAASC





866
RHFSGAALIHARFVMTAASC





867
RHFSAGALIHARFVMTAASC





868
NQGRHFCGGALIHARFVMTAASCYQ





869
NQGRHYCGGALIHARFVMTAASCFQ





870
NQGRHFCGGALIHARFAMTAASCFQ





871
NQGRHFCGGALIHARFIMTAASCFQ





872
NQGRHFCGGALIHARFLMTAASCFQ





873
NQGRHFCGGALIHARFVMTAATCFQ





874
NQGRHFCAAALIHARFVMTAASSFQ





875
NQGRHFCGAALIHARFVMTAASSFQ





876
NQGRHFCAGALIHARFVMTAASSFQ





877
NQGRHFSAAALIHARFVMTAASCFQ





878
NQGRHFSGAALIHARFVMTAASCFQ





879
NQGRHFSAGALIHARFVMTAASCFQ





880
NQGRHFCAAALIHARFVMTAASCFQ





881
NQGRHFCGAALIHARFVMTAASCFQ





882
NQGRHFCAGALIHARFVMTAASCFQ





883
RHFCGGALIHARFVMTAAKS





884
RHFCGGALIHARFVMTAARS





885
RHFCGGALIHARFVMTAAHS





886
RHFSGGALIHARFVMTAAKC





887
RHFSGGALIHARFVMTAARC





888
RHFSGGALIHARFVMTAAHC





889
NQGRHFCGGALIHARFVMTAAKSFQ





890
NQGRHFCGGALIHARFVMTAARSFQ





891
NQGRHFCGGALIHARFVMTAAHSFQ





892
NQGRHFSGGALIHARFVMTAAKCFQ





893
NQGRHFSGGALIHARFVMTAARCFQ





894
NQGRHFSGGALIHARFVMTAAHCFQ





895
RHFCGGALIHARFVMTAAKC





896
RHFCGGALIHARFVMTAARC





897
RHFCGGALIHARFVMTAAHC





898
NQGRHFCGGALIHARFVMTAAKCFQ





899
NQGRHFCGGALIHARFVMTAARCFQ





900
RHFSGGALIHARFVMTAASS





901
NQGRHFSGGALIHARFVMTAASSFQ





902
RHFCGGALIHARFVMTAASS





903
NQGRHFCGGALIHARFVMTAASSFQ





904
RHFSGGALIHARFVMTAASC





905
NQGRHFSGGALIHARFVMTAASCFQ





906
RHFCGGALIHARFVMTAASC





907
NQGRHFCGGALIHARFVMTAASCFQ





908
MRTSYLLLFTLCLLLSEMASGGNFLTGLGHRSDHYNCVSSGGQCLYSACPIFT



KIQGTCYRGKAKCCK





909
YQVIQSWEHWRE





910
YKIIQQWFHWRRV





911
MKFACALLALLGLATSCSFIVFRSEWRALPSECSSRLGHPVRYVVISHTRGSFC



NSFDSCEQQARNVQHYHKNELEWCDVAYNIKEDHTEPIYNPMSIGITFMGNF



MDRVRKAALRAALNLLESGVSRGFLRSNYEVKGH





912
MSRRYTPLAWVLLALLGLGAAQDCGSIVSRGKWGALASKCSQRLRQPVRYV



VVSHTAGSVCNTPASCQRQAQNVQYYHVRERGWCDVGYNFKIGEDGKVYE



GRGWNTKGDHSGPTWNPIAIGISFMGNYMHRVFFASALRAAQSLLACGAARG



YLTPNYEVKGHRDVQQTLSPGDELYKIIQQWPHYRRV





913
NHRSCYRNKGVCAPARCPRNMRQIGTCHGPPVKCCR





914
SRRSCHRNKGVCALTRCPRNMRQIGTCFGPPVKCCR





915
MRVLYLLFSFLFIFLMPLPGVFGGIGDPVTCLKSGAICHPVFCPRRYKQIGTCGL



PGTKCCKKP





916
MRVLYLLFSFLFIFLMPLPGVFGGISDPVTCLKSGAICHPVFCPRRYKQIGTCGL



PGTKCCKKP





917
MRLHHLLLALLFLVLSAGSGFTQGVRNSQSCRRNKGICVPIRCPGSMRQIGTCL



GAQVKCCRRK





918
MRLVVCLVFLASFALVCQGQVYKGGYTRPIPRPPFVRPVPGGPIGPYNGCPVS



CRGISFSQARSCCSRLGRCCHVGKGYSG





919
MRLVVCLVFLASFALVCQGQVYKGGYTRPVPRPPPFVRPLPGGPIGPYNGCPV



SCRGISFSQARSCCSRLGRCCHVGKGYSG





920
EVYKGGYTRPIPRPPPFVRPLPGGPIGPYNGCPVSCRGISFSQARSCCSRLGRCC



HVGKGYS





921
YRGGYTGPIPRPPPIGRPPLRLVVCACYRLSVSDARNCCIKFGSCCHLVK





922
MRLVVCLVFLASFALVCQGQVYKGGYTRPIPRPPPFVRPLPGGPIGPYNGCPVS



CRGISFSQARSCCSRLGRCCHVGKG





923
MRLVVCLVFLASFALVCQGEAYRGGYTGPIPRPPPIGRPPFRPVCNACYRLSVS



DARNCCIKFGSCCHLVKG





924
LLASDEEIQDVSGTWYLKA





925
SSSKEENRIIPGGI





926
GMASKGAIAGKIAKVALKAL





927
KRKFHEKHHSHRGY





928
DSHAKRHHGYKRKFHEKHHSHRGY





929
KRLFKKLKFSLRKY





930
KRLFKELKFSLRKY





931
YGRHSHHKEHFKRKC





932
KRKFHEKHHSHRGYC





933
KRLFKELLFSLRKY





934
KRLFKELKFSLRKY





935
LLLFLLKKRKKRKY





936
KRLFKKLLFSLRKY





937
KRLFKELLKSLRKY





938
KRLFKELKKSLRKY





939
IKISGKWKAQKRFLKMSGC





940
GKWKAFKKAAKKFAKKCS





941
GKWKLFKKAAKKFLKKCS





942
GKLKKKWKAAKKFLKKCS





943
CGGGGGGGGGKWKAFKKAFKKFAKILACG





944
GKWKLFKKAFKKFLKILAG





945
GKWKAFKKAFKKFAKILAG





946
GKWKLFKKAFKKFLKILAC





947
GRLRKKWKAFKKFLKILAC





948
IGKFLHSAKKFAKAFAFVAEIMNS





949
GIGKFLHSAKKFAKAFVAEIMNS





950
GIGKFLHAAKKFAKAFVAEIMNS





951
IGKFLHAAKKFAKAFVAEIMNS





952
GIGKFLHSAKKFGKAFVGEIMNSK





953
QKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCR





954
NQGRHFCGGALIHARYVMTAASCFQ





955
RRLRRIIRKGIRIIKKYG





956
KRLRRIIRKGIHIIKKYG





957
KNLRRIIRKGIRIIKKYG





958
KNLRRIIRKGIHIIKKYG





959
KNLRRIIRKIAHIIKKYG





960
KNLRRIIRKIDHIIKKYG





961
KNLRRIIRKIEHIIKKYG





962
KNLRRIIRKISHIIKKYG





963
KNLRRIIRKITHIIKKYG





964
KNLRRIIRKIGHIIKKYG





965
KNLRRIIRKAIHIIKKYG





966
KNLRRIIRKDIHIIKKYG





967
KNLRRIIRKEIHIIKKYG





968
KNLRRIIRKSIHIIKKYG





969
KNLRRIIRKTIHIIKKYG





970
KNLRRIARKIIHIIKKYG





971
KNLRRIDRKIIHIIKKYG





972
KNLRRIERKIIHIIKKYG





973
KNLRRISRKIIHIIKKYG





974
KNLRRITRKIIHIIKKYG





975
KNLRRIGRKIIHIIKKYG





976
KNLRRAIRKIIHIIKKYG





977
KNLRRDIRKIIHIIKKYG





978
KNLRREIRKIIHIIKKYG





979
KNLRRSIRKIIHIIKKYG





980
KNLRRTIRKIIHIIKKYG





981
KNLRRGIRKIIHIIKKYG





982
MRLHHLLLALLFLVLSAWSGFTQGVGNPVSCVRNKGICVPIRCPGSMKQIGTC



VGRAVKCCRKK





983
NSQSCRRNKGICVPIRCPGSMRQIGTCLGAQVKCCR





984
MKTHYFLLVMICFLFSQMEPGVGILTSLGRRTDQYKCLQHGGFCLRSSCPSNT



KLQGTCKPDKPNCCKS





985
DHYNCVSSGGQCLYSACPIFTKIQGTCYRGKAKCCK





986
MLLLLVENHAEIVVSTVEASAPQPHKNTTHTLSHAPAPQPHKNTKSPVPNLQH



GITEGSLKPQECGPRCTARCSNTQYKKPCLFFCQKCCAKCLCVPPGTYGNKQV



CPCYNNWKTKRGGPKCP





987
MALRELLMMGILLLVCLAKVSSDVNMQKEEDEELRFPNHPLIVRDGNRRLMQ



DIDCGGLCKTRCSAHSRPNVCNRACGTCCVRCKCVPPGTSGNRELCGTCYTD



MITHGNKTKCP





988
MAISKSTVVVVILCFILIQELGIYGEDPHMDAAKKIDCGGKCNSRCSKARRQK



MCIRACNSCCKKCRCVPPGTSGNRDLCPCYARLTTHGGKLKCP





989
MKLVFGTLLLCSLLLSFSFLEPVIAYEDSSYCSNKCADRCSSAGVKDRCVKYC



GICCAECKCVPSGTYGNKHECPCYRDKLNKKGKPKCP





990
MKVAFAAVLLICLVLSSSLELVSMAGSAFCSSKCSKRCSRAGMKDRCMKFCGI



CCSKCNCVPSGTYGNKHECPCYRDMKNSKGKAKCP





991
MKVAFVAVLLICLVLSSSLELVSMAGSAFCSSKCAKRCSRAGMKDRCTRFCGI



CCSKCRCVPSGTYGNKHECPCYRDMKNSKGKPKCP








992
MAGGRGRGGGGGGGVAGGGNLRPWECSPKCAGRCSNTQYKKACLTFCNKC



CAKCLCVPPGTYGNKGACPCYNNWKTKEGGPKCP





993
MESKSPWSLRLLICCAAMVAIALLPQQGGQAACFVPTPGPAPAPPGSSATNTN



ASSAAPRPAKPSAFPPPMYGGVTPGTGSLQPHECGGRCAERCSATAYQKPCLF



FCRKCCAACLCVPPGTYGNKNTCPCYNNWKTKRGGPKCP





994
MASRNKAAALLLCFLFLAAVAASAAEMIAGSGIGDGEGEELDKGGGGGGGH



HKHEGYKNKDGKGNLKPSQCGGECRRRCSKTHHKKPCLFFCNKCCAKCLCV



PPGTYGNKETCPCYNNWKTKKGGPKCP





995
PTHG





996
PVPMR





997
NGGVCIPIR





998
QIGTCFGRPVL





999
EGVRSYLSCWGNRGICLLNRCPGRMRQIGTCLAPRVKCCR





1000
EGVRNFVTCRINRGFCVPIRCPGHRRQIGTCLGPQIKCCR





1001
EGVRNFVTCRINRGFCVPIRCPGHRRQIGTCLGPRIKCCR





1002
EGVRNHVTCRIYGGFCVPIRCPGRTRQIGTCFGRPVKCCRRW





1003
EVVRNPQSCRWNMGVCIPISCPGNMRQIGTCFGPRVPCCR





1004
ERVRNPQSCRWNMGVCIPFLCRVGMRQIGTCFGPRVPCCRR





1005
EGVRNHVTCRINRGFCVPIRCPGRTRQIGTCFGPRIKCCRSW





1006
DFASCHTNGGICLPNRCPGHMIQIGICFRPRVLCCRSW





1007
ILKKWPWWPWPPFFRRK





1008
ILKKWPWWPWPPRRK





1009
ILKKWPWWPWRRWWK





1010
ILKKWPWWPWRWWRR





1011
ILKKWPWWPWWPWRRK





1012
FFKKFPFFPFKKK





1013
FFKKFPFFPFRRK





1014
FFKKWPWWPWRRK





1015
ILKKFPLLPFKKK





1016
ILKKWPWWRWRR





1017
ILPWKWPPWPPWPWRR





1018
ILPWKWFFPPWPWRR





1019
IKWPWYVWL





1020
ILPWKWPWYVRR





1021
ILKKWPWWPWKWKK





1022
ILKKWPWWPWKRR





1023
TLPCLWPWWPWSI





1024
IVPWKWTLWPWRR





1025
ILPWICPWRPSKAN





1026
ILPWKWPWWPWWKKPWRR





1027
ILPWKWPWWPWWPWRR





1028
ILPWKWPWRR





1029
PWKWPWWPWRR





1030
ILPWKWPWWPWKKWK





1031
ILPWKWPWWPWRRWR





1032
ILPWKWPWWPWRKWR





1033
ILPWKKWPWWRWRR





1034
ILKPWKWPWWPWRR





1035
ILKPWKWPWWPWRRKK





1036
NQGRHFCGGALIHARFVMTAAHCFQ





1037
MKTIILILLILGLGIDAKSLEESKADEEKFLRFIGSVIHGIGHLVHHIGVALGDDQ



QDNGKFYGYYAEDNGKHWYDTGDQ





1038
MKTTILILLILGLGINAKSLEERKSEEEKLFKLLGKIIHHVGNFVHGFSHVFGDD



QQDNGKFYGYYAEDNGKHWYDTGDQ





1039
MKTTILILLILGLGINAKSLEERKSEEEKAFKLLGRIIHHVGNFVYGFSHVFGDD



QQDNGKFYGHYAEDNGKHWYDTGDQ





1040
MKTTILILLILGLGINAKSLEERKSEEEKVFHLLGKIIHHVGNFVYGFSHVFGDD



QQDNGKFYGHYAEDNGKHWYDTGDQ





1041
MKTTILILLILGLGINAKSLEERKSEEEKVFQFLGKIIHHVGNFVHGFSHVFGDD



QQDNGKFYGHYAEDNGKHWYDTGDQ





1042
RRRFPWWWPFLRRR





1043
RSGRGECRRQCLRRHEGQPWETQECMRRCRRRGG





1044
QIGTCFGRPVK





1045
FTQGVRNSQSCRRNKGICVPIRCPGSMRQIGTCLGAQVKCCRRK





1046
MGECVRGRCPSGMCCSQFGYCGKGPKYCG





1047
SRAAGLAARLARLAL





1048
MAARAAGLAARLAALALRAL





1049
MAARAAGLAARLAALALRA





1050
MAARAAGLAARLAALALR





1051
MASRAAGLARRLARLARRAL





1052
MASRAAGLARRLARLARRA





1053
MASRAAGLARRLARLARR





1054
MVSRAAGLAARLARLALRAL





1055
MVSRAAGLAARLARLALRA





1056
MVSRAAGLAARLARLALR





1057
ASRAAGLAARLARLALR





1058
MASRAAGLAARLARLALRAL





1059
MASRAAGLAARLARLALRA





1060
MASRAAGLAARLARLALR





1061
HPAFDRK





1062
HPAYDDK





1063
HPDYNAT





1064
HPDYNPD





1065
HPDYNPK





1066
YPCYDEY





1067
HPDYNQR





1068
HPAYNAK





1069
YPCYDPA





1070
HPQYNPR





1071
HPQYNPK





1072
GIGKFLHSAKKFKAFVGEIMN





1073
AAGTTCVTTGWGLTRYTNAN





1074
PHGTQCLAMGWGRVGAHPPP





1075
GNGVQCLAMGWGLLGRNRGI





1076
EAQTRCQVAGWGSQSRSGGR





1077
KPQDVCYVAGWGRMAPMGKY





1078
KPGQTCSVAGWGQTAPLGKS





1079
IIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVLTAAHCWGSNINVTL



GAHNIDRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRRNRNVNPV



ALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSY



DPRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVS



SFLPWIRTTMR





1080
WGRVSMRRGT





1081
CTVAGWGRVSMRRGT





1082
RPGLTLCTVAGWG





1083
HPLYNQR





1084
HPEYNQR





1085
HPNYNQR





1086
HPQFNQR





1087
HPQKNTY





1088
HPQANQR





1089
HHQYNQR





1090
HPQYNPQ





1091
IIGGV





1092
IIGGH





1093
APQYNQR





1094
GKSSGVPPEVFTRFVSSFLPWIRTTMR





1095
FKGDSGGPLLCNNVAHGIVSY





1096
GSYDPRRQICVGDRRERKAA





1097
DTLREVQLRVQRDRQCLRIF





1098
RPGTLCTVAGWGRVSMRRGT





1099
RVRRNRNVNPVALPRAQEGL





1100
HPQYNQRTIQNDIMLLQLSR





1101
RRENTQQHITARRAIRHPQY





1102
TAAHCWGSNINVTLGAHNIQ





1103
QSPAGQSRCGGFLVREDFVL





1104
IIGGRESRPHSRPYMAYLQI





1105
RHPQYNQR





1106
HPQYNQ





1107
HAQYNQR





1108
HPQYNAR





1109
HPQYNQA





1110
HPQYAQR





1111
HPAYNQR





1112
HPAYNPR





1113
HPAYNPK





1114
HPQYNQR





1115
IVGGR





1116
IIGGR





1117
GELKKAWRKVKHAGRRVLDTAKGVGRHYVNNWLNRYR





1118
RVIEVVQGAYRAIRHIPRRIRQGLERIL





1119
YHELRDLLLIVTRIVELLGRE





1120
LLSEVYQILQPILQELSATLQRIREVLR





1121
FLIRQLIELLTWLFSNCRTLLSEVY





1122
RVIEVVQGACRAIRHIPRRSRQGLERIL





1123
RVIEVVQGACRASRHIPRRIRQGLERIL





1124
RVIEVVQGACRAIRHIPRRIEQGLERIL





1125
RVIEVVQGACRAIEHIPRRIRQGLERIL





1126
RVIEVVQGACRAIEHIPRRIEQGLERIL





1127
RVIRVVQGACRAIRHIPRRIRQGLRRIL





1128
KIAGYGLKGLAVIIKICIKGLNLIFEIIK





1129
RIIEFILNLGRICIRIIVALGRLGYGAIR





1130
RIAGYGLRGLAVIPRRICIRGLNLIFEIIR





1131
RIAGYGLRGLAVIIRIICRGLNLIFEIIR





1132
RIAGYGLRGLAVIIRCIIRGLNLIFEIIR





1133
RLLTWLRRTLLSRVYQILQEIL





1134
RLLTWLFSNRRTLLSRVYQILQEIL





1135
RLLTWLFSNCRTLLSRVYQILQPIL





1136
LLSKVYQILQPILQKLSATLQKIKEVLK





1137
RLVERIRQLTASLRQLIPQLIQYVRSLL





1138
LLSRVYQILQPILQRLCATLQRIREVLR





1139
LLSRVYQILQPILQRLSATLQAIREVL





1140
RLVRRIRQLTASRQLIPQLIQYV





1141
RLVERIRQLTASRQLIPQLIQYV





1142
FLIKQLIKLLTWLFSNCKTLLSKVY





1143
YVRSLLTRCNSFLWTLLRILQRILF





1144
FLIRQLIRLLTWLFPNCRTLLSRVY





1145
LLTRCNSFLWTLLRILQRILF





1146
FLIRQLIRLLTWLFSNCRTLL





1147
FLIRQLIRLLTWLFSNCRTLLSEVY





1148
FLIRQLIRQLLTWQPILQYILQ





1149
YHKLKLLLIVTKIVELLGKK





1150
RRGLLEVIRTVILLLRRLRHY





1151
RRGLLRVIRTVILLLDRLRHY





1152
RRGLLEVIRCVILLLDRLRHY





1153
RRGLLEVIRTVILLLRRL





1154
RRGLLRVIRTVILLLDRL





1155
RRGLLEVIRCVILLLDRL





1156
YHRLRDLLLIVTRIVELLGRR





1157
YHRLRDLLLIVCRIVELLGRR





1158
YHRLRDLLLIVCRIVELL





1159
RRGLLEVIRTVILALDRL





1160
RRGLLEVIRTVILALDRLRHY





1161
RRGLLEVIRTVILLLDRLRHY





1162
RRGLLRVIRTVILALDIL





1163
YHRLRDLALIVTRIVELL





1164
RRGLLEVIRTVILPRRLLDRL





1165
YHRLRDLLLIVTRIVELL





1166
YHRLLRDLLIVTRIVELL





1167
YHRLRDLLLIVRRIVCLL





1168
YHRLRDLLLIVTRIVCLL





1169
YHRLRDLLLIVTRIVRLL





1170
YHRLRDLLLIVRRIVELL





1171
YHRLRDLLRIVTRIVELL





1172
YHRLRRLLLIVTRIVELL





1173
YHRLLRDLLIVTRIVELLGRR





1174
YHRLRDLLLIVRRIVCLLGRR





1175
YHRLRDLLLIVTRIVCLLGRR





1176
YHRLRDLLLIVTRIVRLLGRR





1177
YHRLRDLLLIVRRIVELLGRR





1178
YHRLRDLLRIVTRIVELLGRR





1179
YHRLRRLLLIVTRIVELLGRR





1180
LWETLGRVGRWVLAIPRRIRQGLELAL





1181
DLWETLKKGGRWILAIPRRIKQGLELTL





1182
RIRRPIALIWRGGRRLTEWL





1183
WETLPRRIRGGRLWILAI





1184
WILAIPRRIRGGRLWETL





1185
LRRGGRWILAIPREIL





1186
LWETLRRGGRWILAIPREIL





1187
LRRGGRWILAIPRAIL





1188
LWETLRRGGRWILAIPRAIL





1189
LRRGGRWILAIPRRIR





1190
LWRLLRRGGRWILAIPRRIR





1191
LWELLRRGGRWILAIPRRIR





1192
LWETLRRIIRWILAIPRRIR





1193
LWETLRRGCRWILAIPRRIR





1194
LWETLRRGGRWILAIPRRIR





1195
DLWETLRRGCRWILAIPRRIR





1196
DLWETLRRGGRWILAIPRRIR





1197
DLWETLRRIIRWILAIPRRIR





1198
LWRLLRRGGRWILAIPRRIRQGLELTL





1199
LWELLRRGGRWILAIPRRIRQGLELTL





1200
LWETLRRGGRWILAIPRRIRRQIELTL





1201
LWETLRRGGRWILAIPRRIRRGLELTL





1202
LWETLRRGGRWILAIPRRIRQGLRLTL





1203
LWRTLRRGGRWILAIPRRIRQGLELTL





1204
LWETLRRGCRWILAIPRRIRQGLELTL





1205
LWETLRRGGRWILAIPRRIRQGLELCL





1206
LWETLRRGGRWILAIPRRIRQGLELTL





1207
DLWETLRRIIRWILAIPRRIRQGLELCL





1208
DLWETLRRGCRWILAIPRRIRQGLELTL





1209
DLWETLRRGGRWILAIPRRIRQGLELCL





1210
DLWETLRRIIRWILAIPRRIRQGLELTL





1211
KVIEVVQGACKAIKHIPKKIKQGLEKIL





1212
RAIRRAIRGAPRAILRAIL





1213
RAIRRAIRGAPRAIL





1214
LIRRLGQRIRRPIHRIARCAG





1215
LIRELGIRIRRPIHRIARCAG





1216
LIRELGQRIRRPIRRIARCAG





1217
LIRELGQRIRRPIHRIARCIG





1218
LIRELGQRIRRPIHRIARCAI





1219
LIRELGQRIRRPIHRIARCAR





1220
LIRELGQRIRRPIHRIARCAG





1221
LIRRLGQRIRRPIHRIARCAGQVV





1222
LIRELGIRIRRPIHRIARCAGQVV





1223
LIRELGQRIRRPIRRIARCAGQVV





1224
LIRELGQRIRRPIHRIARCIGQVV





1225
LIRELGQRIRRPIHRIARCAGRVV





1226
LIRELRQRIRRPIHRIARCARQVV





1227
LIRELGQRIRRPIHRIARCAGQVV





1228
RIRRPIRRIIRCIGQVVEIVR





1229
RIRRPIHRIIRCIGQVVRIVR





1230
RIRRPIRRIARCAGQVVEIVR





1231
RIRRPIHRIARCIGQVVEIVR





1232
RIRRPIHRIARCAGRVVEIVR





1233
RIRRPIHRIARCAGQVVRIVR





1234
RIRRPIHRIARCAGQVVEIVR





1235
LIRRLGQRIRRPIHRIARCAGQVVEIVR





1236
LIRELGIRIRRPIHRIARCAGQVVEIVR





1237
LIRELGQRIRRPIRRIARCAGQVVEIVR





1238
LIRELGQRIRRPIHRIARCIGQVVEIVR





1239
LIRELGQRIRRPIHRIARCAGRVVEIVR





1240
LIRELGQRIRRPIHRIARCAGQVVRIVR





1241
LIRELGQRIRRPIHRIARCAGQVVEIVR





1242
RRIRHIPRAIRVVQGAC





1243
RVIRVVRGACRAIRHIPRRIR





1244
RACRAIRHIPRRIR





1245
VVQRACRAIRHIPRRIR





1246
GACRAIRRIPRRIRGLERIL





1247
GACRAIRRIPRRIR





1248
VVQGACRAIRRIPRRIRGLERIL





1249
VVQGICRAIRHIPRRIRGLERIL





1250
VVRGACRAIRHIPRRIRGLERIL





1251
VVQRACRAIRRIPRRIR





1252
VVQGICRAIRHIPRRIR





1253
VVRGACRAIRHIPRRIR





1254
RVIEVVQGACRAIRRIPRRIRQGLERIL





1255
RVIEVVQGICRAIRHIPRRIRQGLERIL





1256
RVIEVVRGACRAIRHIPRRIRQGLERIL





1257
RVIRVVQGACRAIRHIPRRIRQGLERIL





1258
RVIEVVQGACRAIRRIPRRIR





1259
RVIEVVQGICRAIRHIPRRIR





1260
RVIEVVRGACRAIRHIPRRIR





1261
RVIRVVQGACRAIRHIPRRIR





1262
RVIEVVQGACRAIRHIPRRIRQGLRRIL





1263
RVIEVVQGACRAIRHIPRRIRQILERIL





1264
RVISVVQGACRAIRRIPRRIRQGLERIL





1265
RVISVVQGACRAIRRIPRRIR





1266
GACRAIRHIPRRIR





1267
VVQGACRAIRHIPRRIR





1268
RVIEVVQGACRAIRHIPRRIR





1269
RIAGYGLRGLAVIIRICIRGLNLIFEIIR





1270
LLSRVYQILQPILQRLSATLQRIREVLR





1271
FLIRQLIRLLTWLFSNCRTLLSRVY





1272
DLWETLRRGGRWILAIPRRIRQGLELTL





1273
RRIYRAIRHIPRRIR





1274
GAYRAIRHIPRRIR





1275
KLKKALRWLARHAK





1276
KWKKALRALARHLK





1277
IRALQRAVRHPRAIRRIYRGWKKAIR





1278
IQRVAQKLKKALRALARHWKRAL





1279
KLKKALRALARHWK





1280
AIANFFERLMKKLIWALMGEAVQT





1281
AIAIFKRIAKINFKALMGEAVQT





1282
AIAKFAKKALKSMLALMGEAVQT





1283
KLKKALRALARHWKGWLRRIGRRIERVGQH





1284
GWLRRIGRRIERVGQHKLKKALRALARHWK





1285
KKIEKAIKHIPKKIKLKKALRALARHWK





1286
RRIYRAIRHIPRRIRGWLRRIGRRIERVGQH





1287
QRAVGWLRRIGRRIERVGQHLRALAGPGVTIGIAHAKSQLW





1288
KLIRKLIRWLRRKIRALQRAVAGPGVTIGIAHAKSQLW





1289
IRALQRAVRHPRAIRRIYRGWKKAIRAGPGVTIGIAHAKSQLW





1290
IQRVAQKLKKALRALARHWKRALAGPGVTIGIAHAKSQLW





1291
QRAVKKIEKAIKHIPKKIKIRALAGPGVTIGIAHAKSQLW





1292
QRAVRRIYRAIRHIPRRIRIRALAGPGVTIGIAHAKSQLW





1293
KLKKALRALARHWKAGPGVTIGIAHAKSQLW





1294
KKIEKAIKHIPKKIKAGPGVTIGIAHAKSQLW





1295
GGGGSGGGGSGGGGS





1296
MGKNGSLCCFSLLLLLLLAGLASGHQVL





1297
MGRIARGSKMSSLIVSLLVVLVSLNLASETTA





1298
GIGKFLREAGKFGKAFVGEIMKP





1299
IGEDVYTPGISGDSLR





1300
AKSRWY





1301
RQIIVFMRKKNFVTKILKKQR





1302
RNSLPKVAYATA





1303
LAKLAVKAIKGAIAGAKSAMG





1304
KAIQTAQGVVAVAPGAKIIGDRINQGVKEIKKFLKWK





1305
RPGGQIAIAIGESIRKKASNELKKATKSLWS





1306
SNMIEGVFAKGFKKASHLFKGIG





1307
SKMIEGVFAKGFKGASHLFKGIG





1308
IIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVLTAAHCWGSNINVTL



GAHNIDRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRRNRNVNPV



ALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLR





1309
GIGGALLSAGKSALKGLAKGLAEHFAN





1310
AAPCFCSGKPGRGDLWILRGTCPGGYGYTSNCYKWPNICCYPH





1311
GIGAAILSAGKSIIKGLANGLAEHF





1312
ATCDALSFSSKWLTVNHSACAIHCLTKGYKGGRCVNTICNCRN





1313
VDKPDYRPRPRPPNM





1314
DDMTMKPTPPPQYPLNLQGGGGGQSGDGFGFAVQGHQKVWTSDNGRHEIGL



NGGYGQHLGGPYGNSEPSWKVGSTYTYRFPNF





1315
AVDLAKIANIANKVLSSLFGK





1316
TAGPAIRASVKQCQKTLKATRLFTVSCKGKNGCK





1317
WKSESLCTPGCVTGALQTCFLQTLTCNCKISK





1318
KRGSGWIATITDDCPNSVFVCC





1319
GDVPPGIRNTICLMQQGTCRLFFCHSGEKKRDICSDPWNRCCVSNRDEEGKEK



PKTDGRSGI





1320
GIGASILSAGKSALKGFAKGLAEHFAN





1321
GLLCYCRKGHCKRGERVRGTCGIRFLYCCPRR





1322
KNYGNGVHCTKKGCSVDWGYAWTNIANNSVMNGLTGGNAGWHN





1323
GKVWDWIKSTAKKLWNSEPVKELKNTALNAAKNFVAEKIGATPS





1324
GLLSGILNTAGGLLGNLIGSLSNGES





1325
GLLSGILNSAGGLLGNLIGSLSNGES





1326
SVLSTITDMAKAAGRAALNAITGLVNQGEQ





1327
GLMSVLGHAVGNVLGGLFKPKS





1328
GGLKKLGKKLEGAGKRVFNAAEKALPVVAGAKALG





1329
GGLKKLGKKLEGVGKRVFKASEKALPVAVGIKALG





1330
RRFPWWWPFLRRPRLRRQAFPPPNVPGPRFPPPNVPGPRFPPPNFPGPRFPPPNF



PGPRFPPPNFPPPFPPPIFPGPWFPPPPPFRPPPFGPPRFPGRR





1331
AGWLRKLGKKIERIGQHTRDASIQVLGIAQQAANVAATAR





1332
GKNGVFKTISHECHLNTWAFLATCCS





1333
PLSCRRKGGICILIRCPGPMRQIGTCFGRPVKCCR





1334
GLLDALSGILGL





1335
GLLGTLGNLLNGLGL





1336
GIIDIAKKLVGGIRNVLGI





1337
GSNKGFNFMVDMIQALSN





1338
GSNKGFNFMVDMINALSN





1339
GSNKGFNFMVDMIQALSK





1340
GLFTFIKCAYKLRAPAVAC





1341
GFFTLIKAANKLINKTVNKEAGKGGLEIMA





1342
GVLGTVKNLLIGAGKSAAQSVLKTLSCKLFNDC





1343
VDKPDYRPRPWPRPN





1344
INNWVRVPPCDQVCSRTNPEKDECCRAHGHAFHATCSGGMQCYRR





1345
GLLSVLGSVAKHVLPHVVPVIAEHL





1346
ALGGLLADVVKSKEQPA





1347
ILGTILGLLKGL





1348
INWKALLDAAKKVL





1349
GLLSSLSSVAKHVLPHVVPVIAEHL





1350
GLWQKIKDKASELVSGIVEGVK





1351
GLLSSLSSVAKHVLPHVVPVIAEHL





1352
GLWQKIKNAAGDLASGIVEGIKS





1353
GLWQKIKSAAGDLASGIVEAIKS





1354
GLWQKIKSAAGDLASGIVEGIKS





1355
GLWEKIREKANELVSGIVEGVK





1356
GLVASIGRALGGLLADVVKSKEQPA





1357
GLVSSIGKALGGLLADVVKTKEQPA





1358
GLLSVLGSVVKHVIPHVVPVIAEHL





1359
GLLSVLGSVAQHVLPHVVPVIAEHL





1360
GLLGVLGSVAKHVLPHVVPVIAEHL





1361
GLWSKIKDVAAAAGKAALGAVNEALGEQ





1362
GLWSTIKQKGKEAAIAAAKAAGQAALGAL





1363
XXKEIXWIFHDN





1364
VDKPDYRPRPWPRPNM





1365
VDKPDYRPRPWPRNMI





1366
MSGGDGRGHNTGAHSTSGNINGGPTGLGVGGGASDGSGWSSENNPWGGGSG



SGIHWGGGSGHGNGGGNGNSGGGSGTGGNLSAVAAPVAFGFPALSTPGAGG



LAVSISAGALSAAIADIMAALKGPFKFGLWGVALYGVLPSQIAKDDPNMMSKI



VTSLPADDITESPVSSLPLDKATVNVNVRVVDDVKDERQNISVVSGVPMSVPV



VDAKPTERPGVFTASIPGAPVLNISVNNSTPEVQTLSPGVTNNTDKDVRPAGFT



QGGNTRDAVIRFPKDSGHNAVYVSVSDVLSPDQVKQRQDEENRRQQEWDAT



HPVEAAERNYERARAELNQANEDVARNQERQAKAVQVYNSRKSELDAANKT



LADAIAEIKQFNRFAHDPMAGGHRMWQMAGLKAQRAQTDVNNKQAAFDAA



AKEKSDADAALSAAQERRKQKENKEKDAKDKLDKESKRNKPGKATGKGKP



VGDKWLDDAGKDSGAPIPDRIADKLRDKEFKNFDDFRKKFWEEVSKDPDLSK



QFKGSNKTNIQKGKAPFARKKDQVGGRERFELHHDKPISQDGGVYDMNNIRV



TTPKRHIDIHRGK





1367
DVLKKIGTVALHAGKAALGAVADTISQ





1368
PDPAKTAPKKKSKKAVT





1369
PDPAKTAPKKGSKKAVTKXA





1370
YSSGYTRPLPKPSRPIFIRPIGCDVCYGIPSSTARLCCFRYGDCCHR





1371
QGCKGPYTRPILRPYVRPVVSYNACTLSCRGITTTQARSCCTRLGRCCHVAKG



YS





1372
QGYKGPYTRPILRPYVRPVVSYNACTLSCRGITTTQARSCSTRLGRCCHVAKG



YS





1373
RWKIFKKIEKVGQNIRDGIVKAGPAVAVVGQAATI





1374
GWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATARG





1375
GWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATAR





1376
GWLKKIGKKIERVGQHTRDATIQTIGVAQQAANVAATLK





1377
VFIDILDKMENAIHKAAQAGIGIAKPIEKMILPK





1378
RWKIFKKIERVGQNVRDGIIKAGPAIQVLGTAKAL





1379
RWKFFKKIERVGQNVRDGLIKAGPAIQVLGAAKAL





1380
RWKVFKKIEKVGRNIRDGVIKAGPAIAVVGQAKAL





1381
RWKVFKKIEKVGRHIRDGVIKAGPAITVVGQATAL





1382
PWNIFKEIERAVARTRDAVISAGPAVRTVAAATSVAS





1383
QRFIHPTYRPPPQPRRPVIMRA





1384
GKIPIGAIKKAGKAIGKGLRAVNIASTAHDVYTFFKPKKRH





1385
SGFVLKGYTKTSQ





1386
AGFVLKGYTKTSQ





1387
GFLSTVKNLATNVAGTVIDTIKCKVTGGC





1388
GGLKKLGKKLEGVGKRVFKASEKALPVLTGYKAIG





1389
GGLKKLGKKLEGVGKRVFKASEKALPVLTGYKAIG





1390
MVTLVLLVFLLLNVVEDEAASFPFSCPTLSGVCRKLCLPTEMFFGPLGCGKGF



LCCVSHF





1391
KWCFRVCYRGICYRRCR





1392
GWLKKIGKKIERVGQNTRDATVKGLEVAQQAANVAATVR





1393
GWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATAR





1394
GWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATAR





1395
GWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATAR





1396
GWLKKLGKRIERIGQHTRDATIQGLGIAQQAANVAATAR





1397
AGWLRKLGKKIERIGQHTRDASIQVLGIAQQAANVAATAR





1398
GWLKKIGKKIERVGQHTRDATIQGLGVAQQAANVAATAR





1399
GNFFKDLEKMGQRVRDAVISAAPAVDTLAKAKALGQ





1400
VFVALILAIAIGQSEAGWLKKIGKKIERVGQHTRDATIQGLGIAQQAANVAAT



AR





1401
QSEAGWLKKIGKKIERVGQHTRDATIQGLGVAQQAPNVAATAR





1402
GWLKKIGKKIERVGQHTRDATIQGLGIAQQAANVAATAR





1403
GWLKKIGKKIERIGQHTRDATIQGVGIAQQAANVAATAR





1404
GWLKKIGKKIERIGQHTRDATIQGLGIAQQAANVAATAR





1405
MRTLAILAAILLFALLAQAKSLQETADDAATQEQPGEDDQDLAVSFEENGLS





1406
CPPCPSCPSCPWCPMCPRCPS





1407
VRNSQSCRRNKGICVPIRCPGSMRQIGTCLGAQVKCCRRK





1408
IIGPVLGLVGKPLESLLE





1409
DPVTCLKNGAICHPVFCPRRYKQIGTCGLPGTKCCK





1410
DTLACRQSHGSCSFVACRAPSVDIGTCRGGKLKCCK





1411
MKWTAAFLVLVIVVLMAQPGECFLGLIFHGLVHAGKLIHGLI





1412
SRRSCHRNKGVCALTRCPRNMRQIGTCFGPPVKCCR





1413
NPVSCARNKGICVPSRCPGNMRQIGTCLGPPVKCCR





1414
SNMIEGVFAKGFKKASHLFKGIG





1415
MKAVFVLLVVGLCIMMMDVATAGFGCPNNYACHQHCKSIRGYCGGYCASW



FRLRCTCYRCGGRRDDVEDIFDIYDNVAVERF





1416
GDVPLGIRNTICRMQQGICRLFFCHSGEKKRDICSDPWNRCCVSNTDEEGKEK



PEMDGRSGI





1417
DLLPPRTPPYQEPASDLKVVDFRRSEGFCQEYCNYMETQVGYCPKKKDACCL



H





1418
VHISHQEARGPSFKICVGFLGPRWARGCSTGN





1419
DLLPPRTPPYQVHISHQEARGPSFKICVGFLGPRWARGCSTGN





1420
GIGGALLSAGKAALKGLAKGFAEHF





1421
QVYKGGYTRPVPRPPPFVRPLPGGPIGPYNGCPVSCRGISFSQARSCCSRLGRC



CHVGKGYS





1422
QVYKGGYTRPIPRPPFVRPVPGGPIGPYNGCPVSCRGISFSQARS CCSRLGRCC



HVGKGYS





1423
GFLDKLKKGASDFANALVNSIKGT





1424
GLWEKIKEKANELVSGIVEGVK





1425
GLWEKIKEKASELVSGIVEGVK





1426
FFHHIFRGIVHVGKSIHKLVTG





1427
MSGGDGRGHNTGAHSTSGNINGGPTGLGVGGGASDGSGWSSENNPWGGGSG



SGIHWGGGSGHGNGGGNGNSGGGSGTGGNLSAVAAPVAFGFPALSTPGAGG



LAVSISAGALSAAIADIMAALKGPFKFGLWGVALYGVLPSQIAKDDPNMMSKI



VTSLPADDITESPVSSLPLDKATVNVNVRVVDDVKDERQNISVVSGVPMSVPV



VDAKPTERPGVFTASIPGAPVLNISVNNSTPAVQTLSPGVTNNTDKDVRPAGFT



QGGNTRDAVIRFPKDSGHNAVYVSVSDVLSPDQVKQRQDEENRRQQEWDAT



HPVEAAERNYERARAELNQANEDVARNQERQAKAVQVYNSRKSELDAANKT



LADAIAEIKQFNRFAHDPMAGGHRMWQMAGLKAQRAQTDVNNKQAAFDAA



AKEKSDADAALSSAMESRKKKEDKKRSAENNLNDEKNKPRKGFKDYGHDYH



PAPKTENIKGLGDLKPGIPKTPKQNGGGKRKRWTGDKGRKIYEWDSQHGELE



GYRASDGQHLGSFDPKTGNQLKGPDPKRNIKKYL





1428
VNHALCAAHCIARRYRGGYCNSKAVCVCR





1429
ATCDLASGFGVGSSLCAAHCIARRYRGGYCNSKAVCVCRN





1430
WNHTLCAAHCIARRYRGGYCNSKAVCVCR





1431
SQWVTPNDSLCAAHCIARRYRGGYCNGKRVCVCR





1432
SQWVTPNDSLCAAHCLVKGYRGGYCKNKICHCR





1433
GNGVLKTISHECNMNTWQFLFTCC





1434
FLPVIAGLAAKVLPKLFCAITKKC





1435
GKVWDWIKSTAKKLWNSEPVKELKNTALNAAKNLVAEKIGATPSE





1436
GKVWDWIKKTAKDVLNSDVAKQLKNKALNAAKNFVAEKIGATPS





1437
GILDTLKNLAKTAGKGILKSLVNTASCKLSGQC





1438
GLFGLAKGSVAKPHVVPVISQLV





1439
SVLGKSVAKHLPHVVPVIAEKT





1440
GLLSVLGSLKLIVPHVVPLIAEHL





1441
GLFGILGSVAKHVLPHVVPVIAEHS





1442
DSIQCFQKNNTCHTNQCPYFQDEIGTCYDRRGKCCQ





1443
ADTLACRQSHGSCSFVACRAPSVDIGTCRGGLKKCCKW





1444
NNEAQCEQAGGICSKDHCFHLHTRAFGHCQRGVPCRT





1445
GIGGALLSAGKSALKGLAKGLAEHFAN





1446
ILGPVLSLVGNALGGLLKNE





1447
ALRSAVRTVARVGRAVLPHVAIADPYVRTPYVHNNPDWSLWRRKRWNQQPT



SQADMLEDALEAQAIEALMQEQ





1448
ALRGALRAVARVGKAILPHVAIANPYVRTPYVHNNPDWSLWRSRRRSGNQQP



TSQAEILEDALEAQAIEALMQEQ





1449
LKCVNLQANGIKMTQECAKEDTKCLTLRSLKKTLKFCASGRTCTTMKIMSLP



GEQITCCEGNMCNA





1450
LLGPVLGLVSNALGGLLKNI





1451
GLLSVFKGVLKGVGKNVAGSLLDQLKCKISGGC





1452
RLPPGFTPWRIAPAIV





1453
FLPMLAKLLSGFLGK





1454
GLFSVVKGVLKGVGKNVAGSLLDQLKCKISGGC





1455
ILGPVLGLVGSALGGLIKKI





1456
ILGPVLSLVGNALGGLIKKI





1457
KIKWFKTMKSLAKFLAKEQMKKHLGE





1458
CYREGGECLQRCIGLFHKIKCCK





1459
FLPKTLRKFFCRIRGGRCAVLNCLGKEEQIGRCSNSGRKCCRKKK





1460
DTIACIENKDTCRLKNCPRLHNVVGTCYEGKGKCCH





1461
DLKHLILKAQLTRCYKFGGFCHYNICPGNSRFMSNCHPENLRCCKNIKQF





1462
DCYCRIPACIAGERRYGTCIYQGRLWAFCC





1463
NPVTCLRSGAICHPGFCPRRYKHIGVCGVSAIKCCK





1464
NPVTCIRSGAICHPGFCPGRYKHIGVCGVPLIKCCK





1465
NPVTCLRSGAICHPGFCPRRYKHIGICGVSAIKCCK





1466
DTLACRQSHGSCSFVACRAPSVDIGTCRGGKLKCCK





1467
TQCRIRGGFCRVGSCRFPHIAIGKCATFISCC





1468
DEEKRENEDEENQEDDEQSEMRRGLRSKIKEAAKTAGKMALGFVNDMAGEQ





1469
EEEKRENEDEENQEDDEQSEMRRGLWSKIKEAAKTAGKMAMGFVNDMVGE



Q





1470
EEEKRENEDEEEQEDDEQSEEKRALWKTLLKGAGKVFGHVAKQFLGSQGQPE



S





1471
EEEKREGENEKEQEDDNQSEEKRGLVSDLLSTVTGLLGNLGGGGLKKI





1472
DEEKRENEDEENQEDDEQSEMRRGLRSKIWLWVLLMIWQESNKFKKM





1473
RDVICLMQHGTCRLFFCHSGEKKSEICSDPWNRCC





1474
LQDAALGWGRRCPRCPPCPNCRRCPRCPTCPSCNCNPK





1475
LQDAALGWGRRCPRCPPCPNCRRCPRCPTCPRCNCNPK





1476
LQDAALGWSRRCPRCPPCPNCRRCPRCPTCPSCNCNPK





1477
DCRFCCGCCTDVSGCGVCCRF





1478
FFFFDEKCSRINGRCTASCLKNEELVALCWKNLKCCVTVQSCGRSKGNQSDE



GSGHMGTRG





1479
DLKHLILKAQLARCYKFGGFCYNSMCPPHTKFIGNCHPDHLHCCINMKELEGS



T





1480
MRLVVCLVFLASFALVCQGQVYKGGYTRPVPRPPFVRPLPGGPIGPYNGCPVS



CRGISFSQARSCCSRLGRCCHVGKG





1481
SLDKRACNFQSCWATCQAQHSIYFRRAFCDRSQCKCVFVRG





1482
VDCRRSEGFCQEYCNYMETQVGYCSKKKDACC





1483
AVGSLKSIGYEAELDHCHTNGGYCVRAICPPSARRPGSCFPEKNPCCKYMK





1484
PRITIDRVVLARESWRFTVTGLGFATLTGQGDRFRRVQRWQHAHGLPRHLFG



WTPMEERPFSLDLTSPASVDVLAGALRRT





1485
KVTEQLKRCWGEYIRGYCRKICRISEIREVLCENGRYCCLNIVELEARRKITKPP



PPE





1486
LALGHMQPGRSEFKRCWKGQGACRTYCTRQETYLHMCPDASLCCLPYGSRP



L





1487
LSGRVLFPLSCIGSSGFCFPFRCPHNREEIGRCFFPIQ





1488
QKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCR





1489
NSVTCSKNGGFCISPKCPPGMKQIGTCGLPGSKCCR





1490
MNNLHRELAPISEAAWAQIEEEASRTLKRYLAARRVVDVPEAKGFGFSAVGT



GHVERIDAPGSDIRAVRRNVLPLVELRVPFTLARDAIDDVERGAGDSDWQPLK



DAAKKIAFAEDRAVFDGYAAAGILGLREGTSNPKLALPSSASDYPAAIAAALN



QLRLAGVNGPYAVVLGAGVYTALSGGDDEGYPVFRHIESLIDGKIVWAPAIEG



GFVLSTRGGDFELDIGQDFSIGYSSHSADSVELYLQESFTFQLLTTEA





1491
MNNLHRELAPITSEAWAAIEEEAGRTFKRHIAGRRVVDVAGPHGVDFSAVGL



GRTTGIAAPDEGVQARQRVVAPLVELRVPFTLSREELDNVERGAKDTDLDAV



KEAARRIAFAEDRAIFEGYPAAGITGIRAAGSNAPITVPDDARLVPEAITQALTA



LRLAGVDGPYSVLLSAELYTEVSETSDHGYPIRTHIERLIPDGEIIWAPAIDGAF



VLTTRGGDYELTLGQDVSIGYLSHDADTVRLYFQQTMQFLVHTAEA





1492
MDLLKRELAPILPAAWDLIDHEATRVLKLHLAGRKVVDFRGPFGWEVAAVNT



GRLRAIERKEGPAVSAGVRLVRPLVEFRAPIRLELAELDAVGRGAQEPNIEDV



VRAAEHAAREEDGAIFNGLAAAGIEGILEVAPHKPVVIPAPEAWPRAVAEARE



VLRAAGVDGPYALALGPKAYDELAAAAEDGYPLRKHIEGQLIDGPIVWAPAL



EGGVLLSTRGGDFELTVGEDLSIGYDGHDRQVVELFLTESFTF





1493
MNNLHRELAPISSAAWEQIEEEVARTFKRSVAGRRVVDVEGPAGPELSAVGT



GHLLDVAAPRELVNARLREVRTIVELTVPFELSRDAIDSVERGARDADWQPAK



EAAQRLAFAEDNAIFDGYPAAGIVGIREGTSNRRLTLPADVGAYPDAISDALE



ALRLAGVDGPYSVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKGVRLYLRETFTFLMLTSEA





1494
MNNLHRELAPISSAAWEQIEEEVARTFKRSVAGRRVVDVEGPAGPELSAVGT



GHLLDVAAPRELVNARLREVRTIVELTVPFELSRDAIDSVERGARDADWQPAK



EAAQRLAFAEDNAIFDGYPAAGIVGIREGTSNRRLTLPADVGAYPDAISDALE



ALRLAGVDGPYSVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKGVRLYLRETFTFLMLTSEA





1495
MNDLMRDLAPISAKAWAEIETEARGTLTVTLAARKVVDFKGPLGWDASSVSL



GRTEALAEEPKAAGSAAVVTVRKRAVQPLIELCVPFTLKRAELEAIARGASDA



DLDPVIEAARAIAIAEDRAVFHGFAAGGITGIGEASAEHALDLPADLADFPGVL



VRALAVLRDRGVDGPYALVLGRTVYQQLMETTTPGGYPVLQHVRRLFEGPLI



WAPGVDGAMLISQRGGDFELTVGRDFSIGYHDHDAQSVHLYLQESMTFRCLG



PEA





1496
PQDEWAELREAARQAADSIRVFRRYIPTTRVGRGVEYVPVEREGVRDAVKLV



EISAKFKISQAALDYAKRTGQPLDAGDALRAAAELALEEDRLVAHTLLNLSNA



LKMAATSWDEPGKAVAEVSKAVAELIKAGAPGPYILFVDPARFAKLVSVYEK



TGVMELTRIKAIVKDVVPTPVVPPSAALLISASPQTLDLVIGADTEVEYLGPED



GKHLFRLWETIAVRV





1497
MNNLHRELAPIASSAWAQIEEEVARTFKRSVAGRRVVDVEGPAGPGLSAVGT



GHLRDVTAPREQVSARLREVRNVVELTVPFELSRDAIDSVERGARDADWQPA



KDAAQRLAFAEDGAIFDGYLAADIVGIREGTSNRKLILPTDVSAYPDAISDALE



ALRLAGVDGPYTVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIVWAPAISG



GCVLSTRGGDYELHLGEDVSIGYTSHTDKVVRLYLRETFTFLMLTSEA





1498
RSDLPVNRTLNIIHRAGVKYSLMEDELLLSKHPLSIIERGRKEKASDWDIPGSIA



NDVIRGIQILETNGYTDPVTIISPELYTRLFRVYDKSGTYEIKLVKHATEIIVSPLI



KGLAVVSKKGFYVMENTPAKVEFLGREGINSDYIIWGKIAPYLIDTNA





1499
MDNLHRKLAPISDAAWAQIEDEAARTLKRYLGARRVVDVHGPEGFGLSAVG



TGHLRPATALAEGVESHRREVNPLLELRVPFTLTRAAIDDVARGSNDSDWQPL



KDAARKIALAEDRLVFLGHGDAGIRGILPETSNPIVALPANVADYPEAVASAV



SELRLAGVNGPYALILGTTAFTAANGGAEDGYPVLKHLERLVDVPVVWSQAL



EGGAVVTTRGGDFDLWLGQDISIGYLSHDAASVTLYLQESLTFQMQTSEA





1500
KRSFTEYTQVIETVSKNKVFLEQLLLANPKLYDVMQKYNAGLLKKKRVKKLF



ESIYKYYKRSYLRS





1501
MNNLHRELAPISSSAWEQIEEEVARTFKRSVAGRRVVDVDGPEGPELSAVGTG



HLVEVAAPREQVNARLREVRTIVELTVPLLLSRDAIDSVERGARDADWQPAK



DAAQRLAFAEDGAIFDGYAAASIVGIREGTSNNKLTLPADVSAYPDAISDALE



ALRLAGVDGPYSVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKVVRLYLRETFTFLMLTSEA





1502
MDILRRENAQFPASIWSAIEKEAGLVFGKHLTGRKVVDFKGGLGIGFSSLPTGR



VISSKEKLGEASVGVRMNTPVIELKIPFSFPESEVEAILREANAFDISSIEKAAKK



VCVAENELVFYGLKKEGIEGLIPSIPHKPIKAKGDEILPAVAEGIKELVNSEIEGP



YALLIQPQYFGKLFGVAGNSGYPLTLKLAELLQGNNIIVAPALKSGALLVSLRG



GDYELYSGMDIGVGYSEKKSTNHELFFFETLTFRINTPEA





1503
NIIKWDQQAIPFYETKVQDNAIIQSDKQVPYPLSIINTLFKVMPDLPKEETQPVF



MKAYLTHSRKEDLLIYREHPLSILQRSKKMNRSDWNIPGNIVNDIVRAYEQVL



SSGYSDVNLIIPPYVHALLYRVVDRTGTMEIELLRHLGNIYVSPNVDTIVVISKQ



VLYVYEKKSTTLENLGRDGVYEVYMLSSELAPYVTDPE





1504
MNNLHRELAPISSAAWEQIEEEVARTFKRSVAGRRVVDVEGPKGPELSAVGT



GHLRDVAAPREHVDARLREVRTIVELTVPFELDRAAIDSVERGARDADWQAA



KEAAQRLAFAEDSAIFDGYPAAGIVGIREGTSNRKLTLPSDVGAYPDAISDALE



ALRLAGVDGPYSVLLGADAYTALSEARDQGYPVIEHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYASHTDKVVRLYLRETLTFLMLTSEA





1505
MNNLHRELAPISRAAWSQIEDEVARTFRRSVAGRRVVDVKGPGGTELSGVGT



GHQTAIAAPQQGVVAKLSEVKSLVELTVPFELQREAIDSVVRGAKDADWQPA



KEAAKQLAYAEDRAIFDGYQAAGIGGIREGSSNPSLALPADVSDYPNAISNAL



EQLRLAGVDGPYSVLLGADAYTALGEARDQGYPVIEHIKRIVNGDIIWAPALA



GGSVLSTRGGDFELHLGEDLSIGYTSHTDTVVRLYLRETLTFLMLTSEA





1506
MNNLYRDLAPISAAAWAQIEEEVARTFKRSVAGRRVVDVKDPGGFGLAAVG



TGHLRGIAAPQKGVDAKLREVKALVELTVPFELQRDEIDAVERGANDADWQP



AKDAATELAYAEDRAIFDGYKAAGIVGIREGSSNSRLELPTDAADYPAAVGRA



LEQLRLAGVDGPYSVLLGADAYTALSEGSDDGYPTIDHIKRIVSGDIIWAPALN



GGCVLSTRGGDFELHLGQDLSIGYQSHTDKVVRLYLRETLTFLMLTSEA





1507
MNNLYRDLAPISAAAWAQIEEEVARTFKRSVAGRRVVDVKDPGGFGLAAVG



TGHLRGIAAPQKGVDAKLREVKALVELTVPFELQRDEIDAVERGANDADWQP



AKDAATELAYAEDRAIFDGYKAAGIVGIREGSSNSRLELPTDAADYPAAVGRA



LEQLRLAGVDGPYSVLLGADAYTALSEGSDDGYPTIDHIKRIVSGDIIWAPALN



GGCVLSTRGGDFELHLGQDLSIGYQSHTDKVVRLYLRETLTFLMLTSEA





1508
NNVFQNKEKNYYEAFYTEEKFKKALKVTTPEAYKSLVDLNIQKDSLNRARYG



YIQRATVKTSPLSYFGKTTYYSLNKKDSEETLQLNNVVKYLILTAAMNDVEV



MNLLRIKINPVFKKINN





1509
IPLIWKDFTLDRRLYEAMRRKNTNVDASAALEAAYTVSSAEEMMILRGITRNG



TTFEKNGLYEGAGQDYSTPKAIGTYGGIQDAVTDVYEMMDDSDVPTDSLRW



NLSMSPNIYNKVNKSRSANDVKEMKDLLELLGTPNNPGNVFKSNTLPSVSTTG





1510
NSVTCSKNGGFCISPKCLPGSKQIGTCSLPGSKCCK





1511
RVGDLPPAIRQELEEFDRYINKQHLVATTLQADYGKHDQLINTIPKDINYLHNK



LMSTKQALKFDSGQLVHLKELNNEITDDISKIMQLILQLSTPGTRLSSSFQLNEF



FVKKIKKYYEILRQYEGVVAELDSILGGLERSCTEGFGNLFNIVEVIKSQYHLF



MELCETMAQLHNEVNKLSK





1512
AIHRALISKRMEGHCEAECLTFEVKIGGCRAELAPFCCKNRKKH





1513
FFDEKCNKLKGTCKNNCGKNEELIALCQKSLKCCRTIQPCGSIID





1514
YYGNGLYCNKEKCWVDWNQAKGEIGKIIVNGWV





1515
QKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCR





1516
NPVTCLRSGAICHPGFCPRRYKHIGTCGLSVIKCCK





1517
DHYNCVRSGGQCLYSACPIYTRIQGTCYHGKAKCCK





1518
DHYNCVSSGGQCLYSACPIFTKIQGTCYGGKAKCCK





1519
NPQSCRWNMGVCIPISFLVNMRQIGTCFGPRV





1520
REYRFHNQLATTEKPEILPRIVSDGIVWARRRWRIRPTDVPRPETGERDVEYLL



RLEGWRTQLGLPAEIYVAQVTPTAMGLRRKKPQWVHFEHPYSLWAAFTHLD



PH





1521
NPLSCRLNRGICVPIRCPGNLRQIGTCFTPSVKCCR





1522
MKVLLAITLVAILGVASGTQFSLCQAPSERRHELVNCVKTHLNEQASQKLSEV



KQRLNCEDLDCVFTKICELSSDTHQEHANTFLPDDVKTDVRAALTQCRPSN





1523
DSYICARKGGTCNLSPCPLYNRVEGTCYRGKAKCCI





1524
DSYICARKGGTCNLSPCPLYNRIEGTCYRGKAKCCI





1525
DSYICARKGGTCNLSPCPLYNRIEGTCYRGKAKCCI





1526
DSYICARKGGTCNLSPCPLYNRVEGTCYRGKAKCCI





1527
MRPMSIACAVAVIIACVCALQSAALPSEVRLDPEVRLEEPEDSEAARSIDQGVA



AALAKETSPEVLFRTKRQSHLSLCRYCCNCCKNKGCGFCCRF





1528
MNNLHRELAPIASSAWAQIEEEVARTFKRSVAGRRVVDVEGPAGPGLSAVGT



GHLRDVTAPREQVSARLREVRNVVELTVPFELSRDAIDSVERGARDADWQPA



KDAAQRLAFAEDGAIFDGYLAADIVGIREGTSNRKLTLPTDVSAYPDAISDALE



ALRLAGVDGPYTVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIVWAPAISG



GCVLSTRGGDYELHLGEDVSIGYTSHTDKVVRLYLRETFTFLMLTSEA





1529
ARTFKRSVAGRRVVDVEGPGGTELSGVGTGHQTAIAAPQQGVVARLAEVKRL



VEFTVPFELQREAIDSVLRGANDADWQPAKDAAKELAYAEDRAIFDGYQAAG



IGGIREGSSNAPLALPADIGDYPHAIGNALEELRLAGVDGPYSVLLGADAYTAL



SEARDQGYPVIEHIKRIVNGDIIWAPALTGGSVLSTRGGDFELHLGEDLSIGYLS



HTDSVVRLYLRETLTFLMLTSEA





1530
MNNLHRELAPISSEAWSQIEEEVARTFKRSVAGRRVVDVKGPGGVDLSGVGT



GHQSTIAAPHHGVIAKLSEVKALVQLTVPFELSRDAIDAVERGANDSDWQAA



KDAAKELAYAEDRAIFDGYKAAGIVGIREGSSNTSLALPADVADYPNAIGGAL



QQLRLAGVDGPYSVLLGADAYTALGEASDQGYPVIEHIKRIVNGEIIWAPALE



GGSVLSMRGGDYELHLGQDVSIGYQSHTDSTVRLYLRETLTFLMLTSEA





1531
NPISCARNRGVCIPIGCLPGMKQIGTCGLPGTKCCR





1532
QIVNCKKNEGFCQKYCNFMETQVGYCSKKKEACC





1533
NLHRNLAPVTEVAWQQIGEEAARTFKRHVAGRRVVDVAGPFGYSYSAHNLG



RVTPIKTSDSRIRAQQRQVNPLVELRFPFTLSRAEVDDVARGSLDSDWQPVKD



AAKAVAFAEDQSIFQGFDEAGIRGLGPSSDNPVLSLPEDPLLIPDAVASALSAL



RLAGVEGPYSVVLDADAYTAVSETRDEGHPVFHHLRDLVAGDIIWAPAISGG



YVLSTRGGDNQLTLGTDLSIGYDSHTATDVTLYLEETFTFASLTAEA





1534
QKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCR





1535
NHRSCHRIKGVCAPDRCPRNMRQIGTCFGPPVKCCR





1536
MFTLKKSLLLLFFLGTISLSLCEEERNAEEERRDYPEERDVEVEKRIIPLPLGYF



AKKT





1537
FTMKKSLLLLELLGTINFSLC





1538
DHYICAKKGGTCNFSPCPLFNRIEGTCYSGKAKCCI





1539
PSVVDQIAKVEDILKRLNLIKRERIQVLKDLKEKILILNKKSIANYEQQLFQQEL



EKYRGFQNRLVQATHKQAALMRELTVAFNGLLQDKRVRAEQSKYESFQRQR



GAVIGRYKRAYQEFLDLEAGLQSAKTWYKEMKETVESLEKNVETFV





1540
QKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCR





1541
IRNPVTCIRSGAICYPRSCPGSYKQIGVCGVSVIKCCKKP





1542
PDFMIAASDADAVVRGEFTPVLGELHLGVNSLDYAYFARLHPHRDDLLREVD



LDFPRPRLLVMAPMEAGANLVPRTQRALVRPQDHLVALTSRVPFPTRGRPLN



GADLTVAEQPDGWEIRVPGGERFDLMEIFAQPLKTALMARVSFFRDEHLPRIS



FGRLVVVREQWRIAADELAFAAVRDTRDRYVHARRWWRRRDLPTRVFVKSP



LERKPFHVDADSPALVELLCAAVRR





1543
MNNLHRELAPIASAAWEQIEEEVARTFKRSVAGRRVVDVEGPKGPALSAVGT



GHLRDVDAPREQVSARLREVRAIVELTVPFFLSRDAIDSVERGARDADWQPA



KDAAQRLAFAEDHAIFDGYAAAGIIGIREGSSNRRLTLPDDVGAYPDAISDALE



ALRLAGVDGPYSVLLGADAYTALSEARDQGYPVIDHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKVVRLYLRETFTFLMLTSEA





1544
MNNLHRELAPISSAAWEQIEEEVARTFKRSVAGRRVVDVEGPAGPELSAVGT



GHLLDVAAPRELVNARLREVRTIVELTVPFELSRDAIDSVERGARDADWQPAK



EAAQRLAFAEDNAIFDGYPAAGIVGIREGTSNRRLTLPADVGAYPDAISDALE



ALRLAGVDGPYSVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKGVRLYLRETFTFLMLTSEA





1545
NNVFQNKEKNYYEAFYTEEKFKKALKVTTPEAYKSLVDLNIQKDSLNRARYG



YIQRATVKTSPLSYFGKTTYYSLNKKDSEETLQLNNVVKYLILTAAMNDVEV



MNLLRIKINPVFKKINN





1546
QKYYCRVRGGRCAVLTCLPKEEQIGKCSTRGRKCCR





1547
RDVICLTQHGTCRLFFCHFGERKAEICSDPWNRCC





1548
DQYICARKGGTCNFSPCPLFTRIDGTCYRGKAKCC





1549
NPQSCHRNKGICVPIRCPGNMRQIGTCLGPPVKCCR





1550
NPVSCVRNKAICVPIRSPANMKQIGSCVGRAVKCCR





1551
GLLSGILGAGKNIVCGLSGLLKLESEII





1552
GLWDTIKQAGKKFFLNVLDKIRCKVAGGCRT





1553
VLSYKEAVLRAIDGINQRSSDANLYRLLDLDPRPTMDGDPDTPKPVSFTVKET



VCPRTTQQSPEDCD





1554
ALSYREAVLRAVDRINERSSEANLYRLLELDPPPKDVEDRGARKPTSFTVKET



VCPRTSPQPPEQCD





1555
GFMDTAKNVAKNVAVTLLDNLKCKITKAC





1556
GLLDTFKNLALNAAKSAGVSVLNSLSCKLFKTC





1557
NSQSCRRNKGICVPIRCPGSMRQIGTCLGAQVKCCR





1558
VLSYKEAVLRAIDGINQRSSDANLYRLLDLDPRPTMDGDPDTPKPVSFTVKET



VCPRTTQQSPEDCD





1559
RRWWFR





1560
RRWFWR





1561
MKCLQSVLVLVLLLAMVSAQNTNTTNTRIGGFAGGSGLLPGPAIGGGIGIPGG



VLLPGSFQGGISGGIIHQYGLDCSGNSLSPQTGNCRYYLRNPVNRRYYCTRNQ



KPAYKCPLLRPDCPDTRSGPPVECYTDNDCGPLDKCCCDACLDHYVCKPAA





1562
MLQQSDALHSALREVPLGVGDIPYNDFHVRGPPPVYTNGKKLDGIYQYGHIET



NDNTAQLGGKYRYGEILESEGSIRDLRNSGYRSAENAYGGHRGLGRYRAAPV



GRLHRRELQPGEIPPGVATGAVGPGGLLGTGGMLAADGILAGQGGLLGGGGL



LGDGGLLGGGGVLGVLGEGGILSTVQGITGLRIVELTLPRVSVRLLPGVGVYL



SLYTRVAINGKSLIGFLDIAVEVNITAKVRLTMDRTGYPRLVIERCDTLLGGIK



VKLLRGLLPNLVDNLVNRVLADVLPDLLCPIVDVVLGLVNDQLGLVDSLIPLG



ILGSVQYTFSSLPLVTGEFLELDLNTLVGEAGGGLIDYPLGWPAVSPKPMPELP



PMGDNTKSQLAMSANFLGSVLTLLQKQHALDLDITNGMFEELPPLTTATLGA



LIPKVFQQYPESCPLIIRIQVLNPPSVMLQKDKALVKVLATAEVMVSQPKDLET



TICLIDVDTEFLASFSTEGDKLMIDAKLEKTSLNLRTSNVGNFDIGLMEVLVEKI



FDLAFMPAMNAVLGSGVPLPKILNIDFSNADIDVLEDLLVLSA





1563
FIGAILPAIAGLVGGLINR





1564
FIGAILPAIAGLVHGLINR





1565
MNNLHRELAPVSASAWQQIEEEVARTFKRSVAGRRVVDVEGPAGPALSAVGT



GHLCDVAAPRELVSARLREVRTIVELTVPFELSRDAIDSVERGARDADWQPAK



DAAQRLAFAEDGAIFDGYAAAGIVGIREGTSNRKLALPADVSAYPDAISDALE



ALRLAGVDGPYSVVLGSDAYTALSEARDQGYPVLGHIKRIVSGEIIWAPAISGG



CVLSTRGGDYELHLGEDVSIGYTSHTDKVVRLYLRETLTFLMLTGEA





1566
MNFTKLFIMVAIAVLLIAGIQPVEAAPRMEIGKRREKLGRNVFKAAKKALPVI



AGYKALG





1567
MKVASVCILLAVLLCSAAVADATVYAYASTCARCKSIGAKYCGYGTLRTKGV



SCDGQTMIRSCADCKARFGRCVDSYITECFL





1568
AFEPHEERALQDERQTKGHRLKRQFSLNFGATHEDGYGTDVNAEALANLWK



SASGNTKLEGSASYMQHFGGVGGDGKARISGNLLFSHNY





1569
NPQSCRWNMGVCIPISCPGNMRQIGTCFGPRVPCCR





1570
FLSLALAALPKFLCLVFKKC





1571
RIVDCKRSEGFCQEYCNYLETQVGYCSKKKDACC





1572
PQSCHRNKGVCVPIRCPRSMRQIGTCLGAPVKCCR





1573
KRSFTEYTQVIETVSKNKVFLEQLLLANPKLYDVMQKYNAGLLKKKRVKKLF



ESIYKYYKRSYLRSTPFGLFSETSIGVFSKSSQYKLMGKTTKGIRLDTQWLIRLV



HKMEVDFSKKLSFTRNNANYKFGDRVFQVYT





1574
GFGVGDSACAAHCIARRNRGGYCNAKTVCVC





1575
MSETEAEASVIGHELFHKYTGRDDMIDKPGLLKMLQDNFPNFLAACDKKGTD



YLANVFEKKDKNRDKKIDFSEFLSLLGDIATDYHKQSHGAPACSEGDQ





1576
RWKFFKKIEKVGQNIRDGIIKAGPAVAVVGQAAAIS





1577
PDFKLPGMKYPIPATTPPFVPKRSRFPIYA





1578
MNFKKILFFVFACLVFTVTAAPEPRWKFFKKIEKVGQNIRDGIIKAGPAVAVV



GQAAAISGK





1579
MKTFSVAVAVAVVLTFICLQESSAVSFTEVQELEEPMSNGSPVAAYEEMSEES



WKMPYASRRWRCRFCCRCCPRMRGCGLCCQRR





1580
LQDAALGWGRRCPRCPPCPRCSWCPRCPTCPRCNCNPK





1581
LQDAALGWGRRCPRCPPCPRCSWCPRCPTCPGCNCNPK





1582
LQDAAVGWGRRCPQCPRCPSCPSCPRCPRCPRCKCNPK





1583
LQDAAVGWGRRCPQCPRCPSCPSCPRCPRCPRCKCNPK





1584
LQDAAVGWGRRCPQCPRCPSCPSCPRCPRCPRCKCNPK





1585
SPLSCRGNRGVCLPIRCPGRLRQIGTCFGPRVPCCR





1586
DDSIQCFQKNNTCHTNQCPYFQDEIGTCYDKRGKCCQKRLLHIRVPRKKKV





1587
CLASPSVFRRLTDPPGDARGRRRLAASLHRYLMRAVGRATPNGLWAGI





1588
KQIASKITIYQGKELQLFRKLVELKLLRQCITIPNNRGIITSIIQFLEEYEVGKEIIP



LLEELHAALHSFEKSSSFERINDWNEIKRILSLLQKGDKKVGSEIIYEDVIFKDV



RKDTITPKIRKSFLEGLADFILLFDVNVRVQYEIAQLFYEKYGKSTEKLSNSNLL



NEVFFREIHQFYPYYQNQKYRYKEAKAKEIQQLDELRDQFLKEFESLILNVDQ



SVEVIDIELLIEKYTSLIPEYIKKDSNISYTLFLQETTDENIVLNNVYDGQEKFISR



FKDFFMPHYETKEYSNYIERVLNEDNCYEVDELFGFNGGIHERKSHNIVNLDV



GYQRFNHKDAKQVRDFKVRYNTERKKIEFLDDNYKICNLVYKSSLVPMFLPGI



LSVMLYLFQSGRLNFDITSLVKEENYVPRITFGNVVLSRKKWKVIMEDLKDIL



ESKLE





1589
HPDIVDYFMKRHNWHFKFFHYEEDDKIKGAYFICNDQNIGILTRRTFPLSSDEI



LIPMAPDLRCFLPDRTNRLSALHQPQIRNAIWKLTRKKQNCLVKEAFSSKFEKT



RRNEYQRFLKKGGSVKSVADCSSDELTHIFIELFRSRFGNTSSCYPADNLANFF



SQLHHLLFGHILYIEGIPCAFDIVLKSESQMNVYFDVSNGAIKNECRPLSPGSIL



MWLN





1590
HPDVVSYFMIHHDWKFDFFHYEKDGDIKGSYFLCNGKQIGIMARRSYPLSSDE



VLIPFSPHARCFFPDKTNKLSIINKQNIINATWKIARKKQNCIIKESFSPKFEKTR



RNEIQRFIRNGGEIKCISQLSDKEISSSYISLFHSRFGGTLPCYEYDNLLMFISHLR



ELMFGHVLFWDNKPCAIDIVLKSESSCNVYYDVPNGAVLNDENCMKLSPGSV



LMWLN





1591
HPDIVDYFMKRHNWHFKFFHYKEDDKIKGAYFICNDQNIGILTRRTFPLSSDEI



LIPMAPDLRCFLPDRTNRLSALHQPQIRNAIWKLTRKKQNCLVKETFSSKFEKR



RRNEYQQFLKKGGSVKSVADCSSDELTHIFIELFQSRFGNTLSCYPADNLATFF



SQLHHLLFGHILYIEGIPCAFDIVLKSESQMNVYFDVSNGAIKNEFRPLSPGSIL



MWLN





1592
KNDAKSIIISEEDFKDVDFTNANLPHSFAIKFNVLNAETEKIQLDAIAGATANLL



IGRFGHGNAAIAEIINEITEHEELQANDSILAEIVHLPESRIGNILSRPEMRNYEM



AYLAKSNKENQFQIKISDLYVSVRNGNIILRSKALNKQIIP





1593
DPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCK





1594
IINGSDCDMHTQPWQAALLLRPNQLYCGAVLVHPQWLLTAAHCRKKVFRVR



LGHYSLSPVYESGQQMFQGVKSIPHPGYSHPGHSNDLMLIKLNRRIRPTKDVR



PINVSSHCPSAGTKCLVSGWGTTKSPQVHFPKVLQCLNISVLSQKRCEDAYPR



QIDDTMFCAGDKAGRDSCQGDSGGPVVCNGSLQGLVSWGDYPCARPNRPGV



YTNLCKFTKWIQETIQANS





1595
MNNLHRELAPISAAAWAQIEEEVARTFKRSVAGRRVVDVEEPGGVELSGVGT



GHLHTIAAPRERVGAKLREVKALVEFTVPFLLRRDAIDAVERGARDADWQPA



KDAAQRLAFVEDSAIFDGYPAAGIVGIREATSNRKIALPSDVGAYPGAIGDAVE



ALRLAGVDGPYSVLLGADAYTALAEAREHGYPVLDHIKRIVSGEIVWAPALS



GGCVLSTRGGDFALHLGEDVSIGYRSHNDEVVHLYLRETFTFLMLTSEA





1596
AIHRALISKRMEGHCEAECLTFEVKIGGCRAELAPFCCKNRKKH





1597
GLDFSQPFPSGEFAVCESCKLGRGKCRKECLENEKPDGNCRLNFLCCRQRI





1598
FIGSALKVLAGVLPSIVSWVKQ





1599
MLRVLMMSLLVVAALGHISPPRPEGCNYYCKKPEGPNKGSNYCCGPEYIPLK



REEKHAGNCPPPLKECTRFPRPPQVCPHDGHCPYNQKCCFDTCLDIHTCKPAH



FYIN





1600
MRVCVMVLALVVVTMARSPPFRPLSCPRPKVDIPGCVNTCQAKDKPGFFYCC



DSKGLNAGTCPKVHLQPYERNVLCDRTQFNYPNHLNCKDDEDCQVFLKCCY



LPDNHQLICRNSEDI





1601
MKVLAVSLAFLLIAGLISTSLAQNEEGGEKELVRVRRGGYYCPFFQDKCHRHC



RSFGRKAGYCGGFLKKTCICVMK





1602
IEGRFKCRRWQWRMKKLGAPSITCVRRAF





1603
MFKCRRWQWRMKKLGAPSITCVRRAF





1604
GKIPVKAIKKAGTAIGKGLRAINIASTAHDVYSFFKPKHKKKH





1605
MKVFFLFAVLFCLVRRNSVHISHQEARGP





1606
PHQTGQLTDLRAQDTAGAEAGLQPTLQLRRLRRRDTHFPICIFCCGCCKTPKC



GLCCIT





1607
MKFFALFSFFVLCVALATAGHLGRPYIGGGGGFNRGGGFHRGGGFHRGGGFH



SGGGFHRGGGFHSGGSFGYRG





1608
MSTPKWNLSISRAVICVIALFASMICAAAHFVGGIHTNAGYVGWYHPDYYNH



DVIGVGNYHPGYGWVAPVYATPTYIIGNTGYNCQTVQQCDSEGNCIQSQNCD





1609
SLWLLLLGLVLPSASAQALSYREAVLRAVDRINDGSSEANLYRLLELDPPPKD



VEDRGARKPASFRVKETVCPRTSQQPLEQCDFKENGLV





1610
AMSLVSCSTAAPAKIPIKAIKTVGKAVGKGLRAINIASTANDVFNFLKPKKRKH





1611
AMSLVSCSTAAPAKIPIKAIKTVGKAVGKGLRAINIASTANDVFNFLKPKKRKH





1612
MEGLFNAIKDTVTAAINNDGAKLGTSIVSIVENGVGLLGKLFGF





1613
MTGLAEAIANTVQAAQQHDSVKLGTSIVDIVANGVGLLGKLFGF





1614
MLQGRQFRSCQSYLRQRGNVLEMATGNPQSQTVEECCESLKDIERKQQQCGC



EAIKHAMRQMQGGQSEEVYRKARMLPRTCGLRSQQCQFNVIFV





1615
PHQTGQLTDLRAQDTAGAEAGLQPTLQLRRLRRRDTHFPICIFCCGCCKTPKC



GFCCKT





1616
MNFSRALFYVFAVFLVCASVMAAPEPRWKIFKKIEKVGQNIRDGIIKAGPAVA



VVGQAATIAHGK





1617
PMFKCWRWQWRWKKLGAM





1618
MKVLAVSLAFLLIAGLISTSLAENDEGGEKELVRVRRGGYYCPFRQDKCHRHC



RSFGRKAGYCGGFLKKTCICV





1619
MTGLAEAIANTVQAAQQHDSVKLGTSIVDIVANGVGLLGKLFGF





1620
SKWFTPNHAACAAHCILLGNRGGHCVGTVCHCR





1621
RRWQWRGIGKFLHSAKKF





1622
MDKKAANGGKEKGPLEACWDEWSRCTGWSSAGTGVLWKSCDDQCKKLGK



SGGECVLTPSTCPFTRTDKAYQCQCKK





1623
AKIPIKAIKTVGKAVGKGLRAINIASTANDVFNFLEPKKRKH





1624
MKALLILGLLLFSVAVQGKVFERCELARSLKRFGMDNFRGISLAN





1625
MKALLILGLLLFSVAVQGKVFERCELARSLKRFGMDNFRGITLAN





1626
GCVWPDGKAITTHKLQTTMQETKALIMGYFKSIATGGAMMAKPQEQLTPVIY



PAV





1627
GCVWPDGKAITTHKLQTTMLETKALIMGYFKSIATGGAMMAKPQEQLTPVIY



PAV





1628
GCVWPDGKAITTHKLQTTMLETKALIMGYFKSIATGGAMMATQDGAVTPVIY



PAV





1629
MRLLWLLVAMVVTVLAAATPTAAWQRPLTRPRPFSRPRPYRPNYG





1630
MFTLKKSLLLLFFLGTINLSLCEEERNADEERRDDPEERAVEVEKRILPILSLIG



GLLGK





1631
NWVKQAPGKGLKWMGWIRTNTGEPTYVDDFKGRFAFSLETSASTAFLQINNL



KNEDTATYFCAITTATSDYYAMDYWGQGTSVTVSS





1632
MEIKYLLTVFLVLLIVSDHCQAFLFSLIPSAISGLISAFKGKRRRDLNAQIDQFK



NFRKRDAELEELLSKLPIY





1633
MEIKYLLTVFLVLLIVSDHCQAFLFSLIPSAISGLISAFKGRRKRDLNGQIDHFK



NFRKRDAELEELLSKLPIY





1634
DKLIGSCVWGAVNYTSDCNGECLLRGYKGGHCGSFANVNCWCET





1635
XTYNGKCYKKDNICKYKAQSGKTAICKCYVKKCPRDGAKCEFDSYKGKCYC





1636
RGGRLCYCRGWICFCVGR









Antimicrobial peptides may be classified by their activity (i.e., the organism in which the AMP functions as a defense mechanism). For example, antiviral AMPs have activity against viruses, antifungal AMPs have activity against fungi. The following remaining AMP classes are recognized: anticancer/tumor AMPs; anti-protist AMPs; antiparasitic AMPs; insecticidal AMPs; spermicidal AMPs; anti-HIV-1 AMPs and chemotactic AMPs. For purposes of this disclosure, insecticidal AMPs will be a focus, and all other classes of AMPs will be described, generally, as non-insecticidal AMPs.


The AMPs for use within the invention include natural or synthetic, peptides, or protein analogs, peptide or protein mimetics, and chemically modified derivatives or salts of active peptides or proteins. The AMPs may be mutants that are readily obtainable by partial substitution, addition, or deletion of amino acids within a naturally occurring or native (e.g., wild-type, naturally occurring mutant, or allelic variant) peptide or protein amino acid sequence. Additionally, biologically active fragments of native peptides or proteins are included. Such mutant derivatives and fragments substantially retain the desired activity of the native peptide or proteins. In the case of peptides or proteins having carbohydrate chains, biologically active variants marked by alterations in these carbohydrate species are also included within the invention.


It is understood by one of ordinary skill in the art that the nucleotide sequence that encodes for the amino acid sequence of any of the AMPs identified herein may be deduced from the amino acid sequence. For purposes of transgenic algae, the deduced nucleotide sequence may be modified to reflect codon bias depending on the algae species used.


Any one or combination of the AMPs of the present invention may be selected or combined to yield effective agents for controlling, inhibiting, reducing and/or preventing rotifer growth within the methods and compositions of the invention.


B. Transgenic Algae


Methods for the transformation of various types of algae are known to those skilled in the art. See, for example, Radakovits et al., Eukaryotic Cell, 9, 486-501 (2010), which is incorporated herein by reference. The transformation of the chloroplast genome was the earliest method and is well documented in the literature (Kindle et al., Proc Natl Acad Sci USA, 88, p. 1721-1725 (1991)). A variety of methods have been used to transfer DNA into microalgal cells, including, but not limited to, agitation in the presence of glass beads or silicon carbide whiskers, electroporation, biolistic microparticle bombardment, and Agrobacterium tumefaciens-mediated gene transfer. A preferred method of transformation for the present invention is biolistic microparticle bombardment, carried out with a device referred to as a “gene gun.”


Different regions of the algae may be targeted for transformation in different embodiments of the invention. Target regions include the nuclear genome, the mitochondrial genome, and the chloroplast genome. The preferred target region can vary depending on the gene being expressed. For example, if an algae has been modified to express a lethal gene that is obtained from a bacterium, it may be preferable to express the lethal gene in the chloroplast or mitochondrion, as these organelles evolved from bacteria and retain many similarities. This can be achieved using a chloroplast expression vector that employs 2 intergenic regions of the chloroplast genome that flank and drive the site-specific integration of a transgene cassette (5′ untranslated region, or 5′ UTR followed by the coding sequence of the protein to be expressed which can drive the biological function desired, followed by a 3′ UTR). The 5′ UTR contains a cis acting site that allows for docking of the RNA polymerase, which drives transcription of the transgene. The 3′ UTR contains sequence that allows for the correct termination of the transcription by RNA polymerase. However, in other cases, expression can be achieved with a gene cassette that employs a eukaryotic promoter sequence upstream of the protein coding sequence and a eukaryotic termination sequence downstream of the protein coding sequence. Suitable algae promoters include, but are not limited to, an endogenous algal promoter or hybrid promoter systems that are capable of driving expression of a transcript in algae.


Genetically modified algae can be transformed to include an expression cassette. An expression cassette is made up of one or more genes and the sequences controlling their expression. The three main components of a nuclear expression cassette are a promoter sequence, an open reading frame expressing the gene, and a 3′ untranslated region, which may contain a polyadenylation signal. The cassette is part of vector DNA used for transformation. The promoter is operably linked to the gene expressed represented by the open reading frame.


The following examples are provided to illustrate certain particular features and/or embodiments. These examples should not be construed to limit the disclosure to the particular features or embodiments described.


EXAMPLES
Example 1
Synthesis of Antimicrobial Peptides

This example provides a list of exemplary AMPs that were synthesized and assessed for their ability to control, inhibit, reduce and/or prevent rotifer growth.


The AMPs of this example were commercially synthesized by GENSCRIPT™. Briefly, solid phase peptide synthesis was employed using Fmoc as a protecting group. Piperidine was used to remove the Fmoc protecting group. Peptides were synthesized from C-terminal to N-terminal, and dicyclohexylcarbodiimide (DCC) was used as the activating agent. Finally, upon completion of synthesizing the individual peptides, a TFA wash was employed to remove the peptide from the column.


In general, the exemplary AMPs provided below in Table 2 vary in length from 13 to 56 amino acids (i.e., “Total # A.A.” column), and originate from a diverse set of organisms including arthropods (e.g., insects), amphibians, fish and mammals (“Origin” column). Further, the column identified as “Activity” in Table 2 provides the known organism(s) for which the activity of the AMP is harmful to (i.e., control, inhibit, reduce and/or prevent growth). The “G+” indicates that the AMP has activity against Gram-positive bacteria, and the “G−” indicates that the AMP has activity against Gram-negative bacteria. As the “Activity” column indicates, as single AMP may have broad activity spectrum against multiple organisms.













TABLE 2








Total



Peptide Name
Amino Acid Sequence
Origin
#A.A.
Activity







Ponericin G1
GWKDWAKKAGGWLKKKGPGMA

Pachycondyla

30
G+; G−; Fungi;



KAALKAAMQ (SEQ ID NO: 232)

goeldii (Ant)


Insects





Ponericin G3
GWKDWLNKGKEWLKKKGPGIMK

Pachycondyla

30
G+; G−; Fungi;



AALKAATQ (SEQ ID NO: 234)

goeldii (Ant)


Insects





Ponericin G4
DFKDWMKTAGEWLKKKGPGILK

Pachycondyla

29
G+; G−; Fungi;



AAMAAAT (SEQ ID NO: 235)

goeldii (Ant)


Insects





Ponericin G6
GLVDVLGKVGGLIKKLLP (SEQ ID

Pachycondyla

18
G+; G−;



NO: 1637)

goeldii (Ant)


Insects





Ponericin L2
LLKELWTKIKGAGKAVLGKIKGLL

Pachycondyla

24
G+; G−; Virus;



(SEQ ID NO: 240)

goeldii (Ant)


Fungi; Insects,






HIV





Ponericin W1
WLGSALKIGAKLLPSVVGLFKKK

Pachycondyla

25
G+; G−; Fungi;



KQ (SEQ ID NO: 241)

goeldii (Ant)


Insects,






Mammalian






cells





Ponericin W3
GIWGTLAKIGIKAVPRVISMLKKK

Pachycondyla

26
G+; G−; Fungi;



KQ (SEQ ID NO: 243)

goeldii (Ant)


Insects,






Mammalian






cells





Ponericin W4
GIWGTALKWGVKLLPKLVGMAQ

Pachycondyla

26
G+; G−; Fungi;



TKKQ (SEQ ID NO: 244)

goeldii (Ant)


Insects,






Mammalian






cells





Ponericin W5
FWGALIKGAAKLIPSVVGLFKKKQ

Pachycondyla

24
G+; G−; Fungi;



(SEQ ID NO: 245)

goeldii (Ant)


Insects,;






Mammalian






cells





Ponericin W6
FIGTALGIASAIPAIVKLFK (SEQ ID 

Pachycondyla

20
G+; Insects,



NO: 246)

goeldii (Ant)


Mammalian






cells





Im-1
FSFKRLKGFAKKLWNSKLARKIRT
Scorpion
56
G+; G−;



KGLKYVKNFAKDMLSEGEEAPPA
venom

Insects



AEPPVEAPQ (SEQ ID NO: 1638)








Cupiennin 1D
GFGSLFKFLAKKVAKTVAKQAAK

Cupiennius

35
G+; G−;



QGAKYVANKHME (SEQ ID NO:

salei (Spider)


Insects



1639)








Lycotoxin I
IWLTALKFLGKHAAKHLAKQQLS
Wolf spider
25
G+; G−; Fungi;



KL (SEQ ID NO: 1640)


Insects





Melittin
GIGAVLKVLTTGLPALISWIKRKR
Honeybee
26
G+; G−; Virus;



QQ
venom

Fungi;



(SEQ ID NO: 1641)


Parasites





Piscidin 1
FFHHIFRGIVHVGKTIHRLVTG
Striped Bass
22
G+; G−; Virus;



(SEQ ID NO: 802)


Fungi





Piscidin 2
FFHHIFRGIVHVGKTIHKLVTG
Striped Bass
22
Virus; Fungi;



(SEQ ID NO: 1642)


Parasites





Piscidin 3
FIHHIFRGIVHAGRSIGRFLTG (SEQ
Striped Bass
22
G+; G−; Virus;



ID NO:803)


Fungi;





W16-CA(1-8)-MA(1-12)
KWKLFKKIGIGKFLHWAKKF (SEQ
Hybrid AMP
20
Virus


Hybrid CecropinA(1-8)-
ID NO: 1643)





Magainin2(1-12)









Temporin A
FLPLIGRVLSGIL (SEQ ID NO: 32)
European
13
G+; Virus




common frog







Temporin-F
FLPLIGKVLSGIL (SEQ ID NO: 36)
European
13
G+; G-




common frog







Temporin-G
FFPVIGRILNGIL (SEQ ID NO:
European
13
G+; G-



1644)
common frog







Temporin-L
FVQWFSKFLGRIL (SEQ ID NO:
European
13
G+; G−; Fungi



248)
common frog







MsrA3
MASRHMFLPLIGRVLSGIL (SEQ ID
Hybrid AMP
19
G−; Fungi



NO: 1645)








Cecropin A
KWKLFKKIEKVGQNIRDGIIKAGP
Hybrid AMP
37
G+; G−; Virus;



AVAVVGQATQIAK (SEQ ID NO:


Parasites



62)








Cecropin B
KWKVFKKIEKMGRNIRNGIVKAG
Giant Silk
35
G+; G−; Virus



PAIAVLGEAKAL (SEQ ID NO: 64)
moth







Magainin 2
GIGKFLHSAKKFGKAFVGEIMNS
African
23
G+; G−; Virus;



(SEQ ID NO: 122)
clawed frog

Fungi;






Parasites





Tachyplesin I
KWCFRVCYRGICYRRCR (SEQ ID
Asian
17
G+; G−; Virus



NO: 144)
horseshoe






crab







Lactoferricin B
FKCRRWQWRMKKLGAPSITCVRR
Cattle
25
G+; G−; Virus;



AF


Fungi;



(SEQ ID NO: 1646)








Dermaseptin-S1
ALWKTMLKKLGTMALHAGKAAL
Leaf frog
34
G+; G−; Virus;



GAAADTISQGTQ (SEQ ID NO:


Fungi;



1647)


Parasites









Example 2
Minimal Inhibitory Concentration (MIC) of Antimicrobial Peptides on Algae

This example provides the minimal inhibitory concentration (MIC) of antimicrobial peptides (AMPs) for algae. The significance of determining the MIC of AMPs for algae relates to the need of having a biocontrol agent (i.e., AMP) for rotifers that does not cause harm to algae. Therefore, the tolerance of algae to the AMPs listed in Table 2 of Example 1 was measured.


Briefly, the algae viability assay used herein measured the “health” of the algae cultures by looking at the color of the algae. A change in color from green algae to brown algae indicates that the algae are negatively impacted and likely no longer viable. A visual assay was used to determine the MIC for the individual AMPs on the algae. In each case, a light microscope with 20× magnification was used to observe algae color.


The effect of insecticidal and non-insecticidal AMPs on three different algae species was measured. The three algae species were Auxenochlorella protothecoides, Chlorella sorokiniana and Chlamydomonas reinhardtii.


Algae cultures were initiated in 96-well plates at an OD 750 of approximately 0.1. Individual algae cultures were incubated with a select AMP at concentrations of 7.8 μg/mL, 15.6 μg/mL, 31.2 μg/mL, 62.5 μg/mL, 0.125 mg/mL, 0.25 mg/mL, 0.5 mg/mL and 1 mg/mL to determine the MIC for individual AMPs against the three different algae species for 5-6 days at room temperature on a continuous lit shaker. The antibiotics hygromycin and paromycin served as positive controls for inhibiting and/or reducing the growth rate of algae. Algae cultured in water or media served as a negative control (i.e., no effect on growth). The algae cultures were monitored by preparing microscopy slides with a small sample taken from the individual wells. The algae slides were then visualized under a 20× magnification microscope for algae viability as measured by algae color.


A summary of the MIC, provided in molar concentration, for each insecticidal and non-insecticidal AMP incubated with the three different algae species is provided below in Table 3 (insecticidal AMPs) and Table 4 (non-insecticidal AMPs). The “ND” indicates that the AMP killed all the algae.










TABLE 3








Minimal Inhibitory Concentration (MIC) of


AMP
Insecticidal AMPs for Three Different Algae Species










(SEQ ID

Chlorella


Chlorella


Chlamydomonas



NO: #)

protothecoides


sorokiana


reinhardtii

















Cupiennin 1D
16.5
μM
65.9
μM
32.9
μM


(1639)


Im-1
9.9
μM
19.7
μM
9.9
μM


(1638)


Lycotoxin-1
44
μM
88
μM
22
μM


(1640)


Ponericin G1
78
μM
155.8
μM
19.5
μM


(232)


Ponericin G3
37
μM
37
μM
9.2
μM


(234)


Ponericin G4
158
μM
79
μM
19.8
μM


(235)


Ponericin G6
274.9
μM
274.9
μM
17.2
μM


(1637)


Ponericin L2
48.5
μM
97
μM
12.1
μM


(240)


Ponericin W1
23.1
μM
46.1
μM
11.5
μM


(241)


Ponericin W3
21.8
μM
87.3
μM
5.5
μM


(243)


Ponericin W4
43.8
μM
87.6
μM
11
μM


(244)


Ponericin W5
12
μM
24
μM
12
μM


(245)












Ponericin W6
No Affect
492.5
μM
61.6
μM


(246)









The data in Table 3 indicates that the insecticidal AMPs (13 AMPs) had an MIC for the three algae species in range of about 5.5 μM to about 493 μM. A higher concentration (or MIC) indicates that the algae species is more tolerant of the AMP.










TABLE 4








Minimal Inhibitory Concentration (MIC) of Non-


AMP
Insecticidal AMPs for Three Different Algae Species










(SEQ ID

Chlorella


Chlorella


Chlamydomonas



NO: #)

protothecoides


sorokiana


reinhardtii
















Melittin
11
μM
11
μM
ND (kills)


(1641)













Piscidin 1
12.2
μM
24.3
μM
12.2
μM


(802)


Piscidin 2
24.6
μM
24.6
μM
12.3
μM


(1642)


Piscidin 3
200.7
μM
100.3
μM
50.2
μM


(803)












W16-CA(1-
ND (kills)
25
μM
12.5
μM


8)-MA(1-


12) (1643)













Temporin A
715.4
μM
715.4
μM
89.4
μM


(32)


Temporin F
365
μM
730.7
μM
91.3
μM


(36)


Temporin G
171.4
μM
342.8
μM
85.7
μM


(1644)


Temporin L
76.2
μM
38.1
μM
19
μM


(248)












MsrA3
59.2
μM
NT
29.6
μM


(1645)













Cecropin A
124.9
μM
124.9
μM
15.6
μM


(62)


Cecropin B
65.2
μM
130.4
μM
16.3
μM


(64)


Magainin 2
101.3
μM
50.7
μM
6.3
μM


(122)












Tachyplesin
6.9
μM
ND (kills)
13.8
μM


I (144)











Lactoferricin
ND (kills)
ND (kills)
~10
μM


B (1646)












Dermaseptin-
18.1
μM
36.9
μM
ND (kills)


S1 (1647)









The data in Table 4 indicates that the insecticidal AMPs (16 AMPs) had an MIC for the three algae species in range of about 6 μM to about 731 μM. A higher concentration (or MIC) indicates that the algae species is more tolerant of the AMP.


Example 3
Effect of Antimicrobial Peptides (AMPs) on Rotifer Motility

This example demonstrates the effect of antimicrobial peptides (AMPs) on rotifer motility and viability.


Briefly, the rotifer motility assay used herein in the presence of a biocontrol agent (e.g., AMP) may be used as a measure of relative rotifer viability and competency. Rotifer diet, of which algae is considered to be an important food source, is one of the key environmental factors that impact the growth and multiplication of rotifers. In effect, the inability of a rotifer to be mobile (i.e., inability to swim toward a food source and/or to have mobile cilia that help trap food) prevents the rotifer from ingesting sufficient nutrients to further grow and reproduce. Thus, any approach that reduces and/or inhibits rotifer motility has a significant impact on an individual rotifer and therefore rotifer populations. With respect to algae cultures, reducing and/or inhibiting rotifer motility prevents and/or reduces any negative impact rotifers have on algae cultures (e.g., open pond systems for algae biomass and biofuel production). In other words, reducing and/or inhibiting rotifer motility reduces and/or prevents rotifers (e.g., infestations) from ingesting and consequently damaging algae cultures use in biofuel production. In general, antimicrobial peptides (AMPs) were shown to have a negative impact on rotifer motility and viability, and therefore a negative impact on limiting rotifers proliferation and population growth.


The effect of the insecticidal and non-insecticidal AMPs of Table 2 (Example 1) on three different rotifer species was measured. The three rotifer species were Adineta vaga and Philodina acuticornis (class Bdelloid rotifers), and Brachionus (Monogononta class). A visual motility assay was used to determine the impact of the individual AMPs on rotifer viability. In each case, a light microscope with 20× magnification was used to observe rotifer motility (activity). FIG. 1 shows a side-by-side comparison of AMP treated and AMP untreated Adineta vaga, Philodina acuticornis and Brachionus rotifers. FIGS. 1A, 1C and 1E show a 20× magnification of Adineta vaga, Philodina acuticornis and Brachionus (untreated), respectively. FIGS. 1B, 1D and 1F show a 20× magnification of Adineta vaga, Philodina acuticornis and Brachionus (AMP treated), respectively. The rotifers in FIGS. 1B, 1D and 1F had limited to no mobility, the morphology of the rotifers treated with AMPs compared to the untreated rotifers (FIGS. 1A, 1C and 1E) indicates that the rotifers are unhealthy and/or dead.


Rotifer cultures were initiated in 12-well or 24-well plates at a density of approximately 100-200 rotifers/mL. The 12-well plates contained a volume of 1 mL per well, and the 24-well plates contained a volume of about 0.25 mL to about 0.35 mL per well. Individual rotifer cultures (individual wells) were incubated with a select AMP at a concentration of 0.5 mg/mL (or a range of about 78 μM to about 365 μM) for 18, 21 and 24 hours at room temperature. The rotifer cultures were monitored by preparing microscopy slides with a small sample taken from the individual wells. The slides were then visualized under a 20× magnification microscope for rotifer motility. The range of visual motility was assessed as follows: a non-motile rotifer (no movement observed) was scored as “+++” (high negative impact of AMP on rotifer motility); a rotifer with limited motility (compared to rotifers not treated with an AMP) was scored as “++” (medium negative impact of AMP on rotifer motility); a rotifer with motility slightly below that of a non-treated AMP rotifer was scored as “+” (low negative impact of AMP on rotifer motility); and a rotifer having motility comparable to a rotifer not treated with an AMP was scored as “no kill” (“NK”) (no negative impact of AMP on rotifer motility). The scoring system was based on observing a subset of the rotifer population from each well. The impact on the subset of rotifers observed served as a representative of the impact on the entire rotifer population for that particular AMP treatment.


A summary of the motility assay (or “Kill Assay”) for each insecticidal and non-insecticidal AMP incubated with the three different rotifer species for the 24 hour time point is provided below in Table 5 (insecticidal AMPs) and Table 6 (non-insecticidal AMPs). The 18 and 21 hour time points gave similar results to the 24 hour time point.











TABLE 5









“Kill” Efficiency of Insecticidal AMPs


AMP
Molar
for Three Different Rotifer Species


(SEQ ID
Concentration
(24 hr time point)











NO: #)
at 0.5 mg/mL

Philodina


Adineta vaga


Brachionus
















Cupiennin 1D
131.7
μM
+++
+++
+++/++


(1639)


Im-1
78.8
μM
+++
+++
+++


(1638)


Lycotoxin-1
175.8
μM
+++
+++
+++


(1640)


Ponericin G1
155.75
μM
+++
+++
+++


(232)


Ponericin G3
147.8
μM
+++
+++
+++


(234)


Ponericin G4
158
μM
+++/++
+++/++
+++/++


(235)


Ponericin G6
274.85
μM
+++/++
+++/++
+++


(1637)


Ponericin L2
193.95
μM
+++
+++
+++/++


(240)


Ponericin W1
184.5
μM
+++
+++
+++


(241)


Ponericin W3
174.55
μM
+++
+++
+++


(243)


Ponericin W4
175.3
μM
+++
+++
+++


(244)


Ponericin W5
192.15
μM
+++
+++
+++


(245)


Ponericin W6
246.25
μM
++
++
+++


(246)









The data in Table 5 indicates that the insecticidal AMPs (13 AMPs) had a medium (“++”) to high (“+++”) negative impact on the motility, and therefore viability, of all three rotifer species. Twelve of the 13 AMPs had a high negative impact on all three rotifer species.











TABLE 6









“Kill” Efficiency of Non-Insecticidal


AMP
Molar
AMPs at 0.5 mg/mL for Three Different


(SEQ ID
Concentration
Rotifer Species (24 hr time point)











NO: #)
at 0.5 mg/mL

Philodina


Adineta vaga


Brachionus
















Melittin
175.6
μM
+++
+++
+++/++


(1641)


Piscidin 1
194.4
μM
+++
+++
+++


(802)


Piscidin 2
196.5
μM
+++
+++
+++


(1642)


Piscidin 3
200.65
μM
+++
+++
+++


(803)


W16-CA(1-
199.7
μM
+++
+++
+


8)-MA(1-


12) (1643)


Temporin A
357.72
μM
NK
+
++


(32)


Temporin F
365
μM
NK
NK
+/++


(36)


Temporin G
342.75
μM
NK
NK
+


(1644)


Temporin L
304.7
μM
+++
+++
+++


(248)


MsrA3
236.8
μM
+++
+++
+


(1645)


Cecropin A
124.85
μM
++
+++
++/+++


(62)


Cecropin B
130.35
μM
+++/++
+++
++/+++


(64)


Magainin 2
202.7
μM
+++
+++
+


(122)


Tachyplesin
220.4
μM
+++
+++/++
NK


I (144)


Lactoferricin
160
μM
+++
+++
+++


B (1646)


Dermaseptin-
144.7
μM
+++
+++
+++


S1 (1647)









The data in Table 6 indicates that the non-insecticidal AMPs (16 AMPs) had greater range of impact on the motility, and therefore viability, of the three rotifer species when compared to the insecticidal AMPs of Table 5. The impact of the non-insecticidal AMPs on rotifers ranged from “no kill” (“NK”), or no negative impact on motility (viability), to high (“+++”) negative impact on motility (viability) for all three rotifer species. In the cases where a single rotifer species was not impacted negatively by the presence of an AMP, one or more of the other rotifer species were negatively impacted (see for example Temporin-F in Table 6). Thirteen of the 16 AMPs had at least a high negative impact (“+++”) on motility (viability) in at least one rotifer species.


In summary, these data indicate that the introduction of an AMP (insecticidal or non-insecticidal) has a negative impact on the motility, and therefore viability, of one or more rotifer species. Moreover, in comparing the AMP concentrations of Tables 3 and 4 (algae viability/tolerance of the AMP) with the AMP concentrations of Tables 5 and 6 (rotifer motility), there are overlapping concentrations of AMP indicating where the AMP has a negative impact on the motility, and therefore viability of a rotifer, yet algae are tolerant to the AMP, and remain viable. By way of example, the AMPs Ponericin W6, Temporin A and Temporin F, are highly tolerated by algae, but have a high negative impact on rotifer motility, and therefore viability.


These data indicate that AMPs may be useful in removing and/or preventing rotifer infestations in algae cultivations by reducing and/or inhibiting rotifer motility, and therefore controlling, inhibiting, reducing and/or preventing rotifer growth.


Example 4
Expression Vector for Transgenic Algae Expressing an AMP

This example provides an exemplary expression vector that can be used to engineer transgenic algae to express an antimicrobial peptide (AMP).


An exemplary expression vector (pCPSR24) is shown in FIG. 2. Each antimicrobial peptide encoding sequence is codon-optimized for the algae species in which the expression vector is introduced. Further, an additional start codon (ATG encoding the amino acid methionine) is introduced into the AMP nucleotide sequence. The AMP nucleotide sequence is cloned into the vector multiple cloning site (MCS) via the NheI and AvrII restriction enzyme sites. The AMP nucleotide sequence is operably linked to a promoter (e.g., LacZ), which will drive the expression of the AMP in the algae.


The following nucleotide sequences encoding an AMP are cloned into the pCPSR24 vector via the NheI and AvrII restrictions sites:









M-Ponericin G4 (codon optimized for C. proto-



thecoides)



(SEQ ID NO: 1648)


GCTAGCATGGACTTCAAGGACTGGATGAAGACCGCCGGCGAGTGGCTGAA





GAAGAAGGGCCCCGGCATCCTGAAGGCCGCCATGGCCGCCGCCACCTGAC





CTAGG





M-Ponericin W3 (codon optimized for C. proto-



thecoides)



(SEQ ID NO: 1649)


GCTAGCATGGGCATCTGGGGCACCCTGGCCAAGATCGGCATCAAGGCCGT





GCCCCGCGTGATCAGCATGCTGAAGAAGAAGAAGCAGTGACCTAGG





M-Ponericin W6 (codon optimized for C. proto-



thecoides)



(SEQ ID NO: 1650)


GCTAGCATGTTCATCGGCACCGCCCTGGGCATCGCCAGCGCCATCCCCGC





CATCGTGAAGCTGTTCAAGTGACCTAGG





M-Ponericin G6 (codon optimized for C. proto-



thecoides)



(SEQ ID NO: 1651)


GCTAGCATGGGCCTGGTGGACGTGCTGGGCAAGGTGGGCGGCCTGATCAA





GAAGCTGCTGCCCTGACCTAGG






The expression vector is transformed into the algae, which then express the AMP. The algae expressing the AMP have a defense to rotifers, whereby the AMP inhibits, reduces and/or prevents rotifer growth, thus preventing rotifer infestation from damaging the algae.


In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as limiting the scope of the invention. Rather, the scope of the invention is defined by the following claims. We therefore claim as our invention all that comes within the scope and spirit of these claims.

Claims
  • 1. A method for inhibiting the growth or reducing the growth rate of one or more rotifers, comprising contacting the one or more rotifers with an isolated antimicrobial peptide (AMP), wherein the growth or growth rate of the one or more rotifers is inhibited by the AMP compared to the growth of the one or more rotifers absent the AMP.
  • 2. The method of claim 1, wherein the AMP is from about 5 to about 200 amino acids in length.
  • 3. The method of claim 1, wherein the AMP is an insecticidal AMP.
  • 4. The method of claim 1, wherein the AMP is a non-insecticidal AMP.
  • 5. The method of claim 1, wherein the concentration of the AMP is about 0.5 μM to about 500 μM.
  • 6. The method of claim 1, wherein the concentration of the AMP is about 75 μM to about 370 μM.
  • 7. The method of claim 1, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647.
  • 8. The method of claim 1, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.
  • 9. A method for inhibiting or preventing a rotifer infestation of an algae culture, comprising contacting an algae culture with an isolated antimicrobial peptide (AMP), wherein the concentration of the AMP in the algae culture is sufficient to inhibit the growth of and/or reduce the rate of growth of a rotifer in the algae culture.
  • 10. The method of claim 9, wherein the AMP does not substantially inhibit the growth of the algae.
  • 11. The method of claim 9, wherein the AMP is from about 5 to about 200 amino acids in length.
  • 12. The method of claim 9, wherein the AMP is an insecticidal AMP.
  • 13. The method of claim 9, wherein the AMP is a non-insecticidal AMP.
  • 14. The method of claim 9, wherein the concentration of the AMP in the algae culture is about 0.5 μM to about 500 μM.
  • 15. The method of claim 9, wherein the concentration of the AMP in the algae culture is about 75 μM to about 370 μM.
  • 16. The method of claim 9, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647.
  • 17. The method of claim 9, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.
  • 18. A transgenic algae comprising an expression vector, wherein the expression vector comprises a heterologous promoter operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP).
  • 19. The transgenic algae of claim 18, wherein the nucleotide sequence encoding the AMP is codon-optimized for expression in algae.
  • 20. The transgenic algae of claim 18, wherein the AMP does not substantially inhibit the growth of the algae.
  • 21. The transgenic algae of claim 18, wherein the AMP is from about 5 to about 200 amino acids in length.
  • 22. The transgenic algae of claim 18, wherein the AMP is an insecticidal AMP.
  • 23. The transgenic algae of claim 18, wherein the AMP is a non-insecticidal AMP.
  • 24. The transgenic algae of claim 18, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 1-1647.
  • 25. The transgenic algae of claim 18, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 144, 232, 234, 235, 240, 241, 243-246, 248, 802, 803 and 1638-1647.
  • 26. The transgenic algae of claim 18, wherein the AMP comprises the amino acid sequence of any one of SEQ ID NOs: 32, 36, 62, 64, 122, 232, 235, 246, 803 and 1637.
  • 27. The transgenic algae of claim 19, wherein the nucleotide sequence encoding the AMP comprises any one of SEQ ID NOs: 1648-1651.
  • 28. An expression vector comprising a promoter operatively linked to a nucleotide sequence encoding an antimicrobial peptide (AMP), wherein the nucleotide sequence is codon-optimized for expression in algae.
  • 29. The expression vector of claim 28, wherein the nucleotide sequence encoding the AMP comprises any one of SEQ ID NOs: 1648-1651.
CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No. 61/807,126, filed Apr. 1, 2013, which is herein incorporated by reference in its entirety.

ACKNOWLEDGMENT OF GOVERNMENT SUPPORT

This invention was made with government support under Contract No. DE-AC52-06NA25396 awarded by the U.S. Department of Energy. The government has certain rights in the invention.

Provisional Applications (1)
Number Date Country
61807126 Apr 2013 US