ADENINE DEAMINASES AND COMPOSITIONS, SYSTEMS, AND METHODS THEREOF

Abstract

The present disclosure provides components, compositions, methods, and systems thereof for nucleic acid editing. Particularly, the invention relates to adenine deaminases, fusion proteins of the adenine deaminases, systems including the adenine deaminases, and methods of using thereof.

Claims

1. A polypeptide comprising an adenosine deaminase having an amino acid sequence with at least 75% identity to SEQ ID NO: 2.

2. The polypeptide of claim 1, wherein the adenosine deaminase has an amino acid sequence with at least 90% identity to SEQ ID NO: 2.

3. The polypeptide of claim 1, wherein the adenosine deaminase has an amino acid sequence of SEQ ID NO: 2.

4. A fusion protein comprising the polypeptide of claim 1 and a nucleic acid binding domain.

5. The fusion protein of claim 4, wherein the nucleic acid binding domain is a Clustered Regularly Interspaced Short Palindromic Repeats associated (Cas) protein or a fragment or variant thereof capable of nucleic acid binding.

6. The fusion protein of claim 5, wherein the Cas protein is at least partially catalytically inactivated.

7. The fusion protein of claim 5, wherein the Cas protein is a catalytically inactivated Cas9.

8. The fusion protein of claim 4, further comprising a linker separating the polypeptide and the nucleic acid binding domain, a localization sequence, a tag sequence, a protein transduction domain sequence, or a combination thereof.

9. A nucleic acid encoding the polypeptide of claim 1 or a fusion protein thereof.

10. A system comprising a polypeptide of claim 1 and a nucleic acid binding polypeptide, or one or more nucleic acids encoding thereof, wherein the polypeptide and the nucleic acid binding polypeptide are fused as a single protein or wherein the polypeptide is linked to a first half of a binding pair and the nucleic acid binding polypeptide is linked to a second half of the binding pair.

11. The system of claim 10, wherein the nucleic acid binding polypeptide is a Cas protein.

12. The system of claim 11, wherein the Cas protein is at least partially catalytically inactivated.

13. The system of claim 11, wherein the Cas protein is catalytically inactivated Cas9.

14. The system of claim 11, further comprising at least one guide RNA or a nucleic acid encoding thereof.

15. A cell comprising a polypeptide of claim 1, a fusion protein or system comprising the polypeptide, or one or more nucleic acids encoding the polypeptide or fusion protein.

16. A method of modifying a target nucleic acid comprising contacting the target nucleic acid with a polypeptide of claim 1, or a fusion protein or system comprising the polypeptide.

17. The method of claim 16, wherein the method installs or reverses one or more point mutations in the target nucleic acid.

18. The method of claim 16, wherein the target nucleic acid is in a cell and the contacting comprises introducing the polypeptide, fusion protein or system comprising the polypeptide, or one or more nucleic acids encoding the polypeptide or fusion protein into the cell.

19. The method of claim 18, wherein the cell is in vitro, ex vivo, or in vivo.

20. The method of claim 19, wherein the introducing comprises administering to a subject.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] FIG. 1 is a graph of the A to G editing efficiency of deaminase enzymes linked to Cas9n as disclosed herein (SEQ ID NOs: 1-23, as indicated).

[0027] FIG. 2 is a graph showing the specificity of the deaminase enzymes linked to Cas9n on the target strand as disclosed herein (SEQ ID NOs: 1-23, as indicated). Efficiency of nucleotide changes at each position on the target strand, including at the target site, are shown.

[0028] FIG. 3 is graphs showing the A to G editing efficiency of deaminase enzymes as disclosed herein (SEQ ID NOs: 1-2, as indicated) at three different target sites (HEK2, T39, and CD3G1) using when linked to two different nucleases, OpenCRISPR-1 (Ruffolo, et al., bioRxiv 2024.04.22.590591) and spCas9, both partially catalytically inactivated (nickases).

[0029] FIG. 4 is graphs of the A to G editing efficiency of deaminase enzymes as disclosed herein (SEQ ID NOs: 1-23 and 574-776, as indicated) when tethered to spCas9n.

[0030] FIG. 5 is graphs of the A to G editing efficiency of deaminase enzymes, as indicated, when tether to spCas9n. The editing efficiency was determined by NGS analysis with CRISPResso.

DETAILED DESCRIPTION

[0031] The disclosed polypeptides, compositions, systems, kits, and methods include deaminases useful for nucleic acid modification.

[0032] Section headings as used in this section and the entire disclosure herein are merely for organizational purposes and are not intended to be limiting.

Definitions

[0033] The terms comprise(s), include(s), having, has, can, contain(s), and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. As used herein, comprising a certain sequence or a certain SEQ ID NO usually implies that at least one copy of said sequence is present in recited peptide or polynucleotide. However, two or more copies are also contemplated. The singular forms a, and, and the include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments comprising, consisting of, and consisting essentially of, the embodiments or elements presented herein, whether explicitly set forth or not.

[0034] For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated.

[0035] Unless otherwise defined herein, scientific, and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. For example, any nomenclature used in connection with, and techniques of cell and tissue culture, molecular biology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those that are well known and commonly used in the art. The meaning and scope of the terms should be clear; in the event, however of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular.

[0036] As used herein, nucleic acid or nucleic acid sequence refers to a polymer or oligomer of pyrimidine and/or purine bases, preferably cytosine, thymine, and uracil, and adenine and guanine, respectively (See Albert L. Lehninger, Principles of Biochemistry, 793-800 (Worth Pub. 1982)). The present technology contemplates any deoxyribonucleotide, ribonucleotide, or nucleoprotein component, and any chemical variants thereof, such as methylated, hydroxymethylated, or glycosylated forms of these bases, and the like. The polymers or oligomers may be heterogenous or homogenous in composition and may be isolated from naturally occurring sources or may be artificially or synthetically produced. In addition, the nucleic acids may be DNA or RNA, or a mixture thereof, and may exist permanently or transitionally in single-stranded or double-stranded form, including homoduplex, heteroduplex, and hybrid states. In some embodiments, a nucleic acid or nucleic acid sequence comprises other kinds of nucleic acid structures such as, for instance, a DNA/RNA helix, peptide nucleic acid (PNA), morpholino nucleic acid (see, e.g., Braasch and Corey, Biochemistry, 41 (14): 4503-4510 (2002) and U.S. Pat. No. 5,034,506), locked nucleic acid (LNA; see Wahlestedt et al., Proc. Natl. Acad. Sci. U.S.A., 97:5633-5638 (2000)), cyclohexenyl nucleic acids (sec Wang, J. Am. Chem. Soc., 122: 8595-8602 (2000)), and/or a ribozyme. Hence, the term nucleic acid or nucleic acid sequence may also encompass a chain comprising non-natural nucleotides, modified nucleotides, and/or non-nucleotide building blocks that can exhibit the same function as natural nucleotides (e.g., nucleotide analogs); further, the term nucleic acid sequence as used herein refers to an oligonucleotide, nucleotide or polynucleotide, and fragments or portions thereof, and to DNA or RNA of genomic or synthetic origin, which may be single or double-stranded, and represent the sense or antisense strand. The terms nucleic acid, polynucleotide, nucleotide sequence, and oligonucleotide are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof.

[0037] As used herein, peptide, polypeptide, or protein refer to a sequence of two or more amino acids linked by peptide bonds. The polypeptide can be natural, synthetic, or a modification or combination of natural and synthetic. The peptide or polypeptide may be modified by the addition of sugars, lipids or other moieties not included in the amino acid chain. The terms polypeptide, oligopeptide, and peptide are used interchangeably herein. The peptide(s) may be produced by recombinant genetic technology or chemical synthesis. The peptide(s) may be isolated and purified by any number of standard methods including, but not limited to, differential solubility (e.g., precipitation), centrifugation, chromatography (e.g., affinity, ion exchange, and size exclusion), or by any other standard techniques known in the art.

[0038] The term amino acid or any amino acid as used here refers to any and all amino acids, including naturally occurring amino acids (e.g., a-amino acids), unnatural amino acids, modified amino acids, and non-natural amino acids. It includes both D-and L-amino acids. Natural amino acids include those found in nature, such as, e.g., the 23 amino acids that combine into peptide chains to form the building-blocks of a vast array of proteins. These are primarily L stereoisomers, although a few D-amino acids occur in bacterial envelopes and some antibiotics. For the most part, the names of naturally occurring and non-naturally occurring aminoacyl residues used herein follow the naming conventions suggested by the IUPAC Commission on the Nomenclature of Organic Chemistry and the IUPAC-IUB Commission on Biochemical Nomenclature as set out in Nomenclature of -Amino Acids (Recommendations, 1974) Biochemistry, 14(2), (1975). To the extent that the names and abbreviations of amino acids and aminoacyl residues employed in this specification and appended claims differ from those suggestions, they will be made clear to the reader. Throughout the present specification, unless naturally occurring amino acids are referred to by their full name (e.g., alanine, arginine, etc.), they are designated by their conventional three-letter or single-letter abbreviations (e.g., Ala or A for alanine, Arg or R for arginine, etc.). The term L-amino acid, as used herein, refers to the L isomeric form of a peptide, and conversely the term D-amino acid refers to the D isomeric form of a peptide (e.g., Dphe, (D)Phe, D-Phe, or .sup.DF for the D isomeric form of Phenylalanine). Amino acid residues in the D isomeric form can be substituted for any L-amino acid residue, as long as the desired function is retained by the peptide.

[0039] Nucleic acid or amino acid sequence identity, as described herein, can be determined by comparing a nucleic acid or amino acid sequence of interest to a reference nucleic acid or amino acid sequence. A number of mathematical algorithms for obtaining the optimal alignment and calculating identity between two or more sequences are known and incorporated into a number of available software programs. Examples of such programs include CLUSTAL-W, T-Coffee, and ALIGN (for alignment of nucleic acid and amino acid sequences), BLAST programs (e.g., BLAST 2.1, BL2SEQ, and later versions thereof) and FASTA programs (e.g., FASTA3x, FAS, and SSEARCH for sequence alignment and sequence similarity searches). Sequence alignment algorithms also are disclosed in, for example, Altschul et al., J. Molecular Biol., 215(3): 403-410 (1990), Beigert et al., Proc. Natl. Acad. Sci. USA, 106 (10): 3770-3775 (2009), Durbin et al., eds., Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids, Cambridge University Press, Cambridge, UK (2009), Soding, Bioinformatics, 21(7): 951-60 (2005), Altschul et al., Nucleic Acids Res., 25(17): 3389-3402 (1997), and Gusfield, Algorithms on Strings, Trees and Sequences, Cambridge University Press, Cambridge UK (1997)).

[0040] The term gene refers to a nucleic acid sequence that comprises control and coding sequences necessary for the production of a gene product (e.g., an RNA having a non-coding function (e.g., a ribosomal or transfer RNA), a polypeptide, or a precursor of any of the foregoing). The RNA or polypeptide can be encoded by a full-length coding sequence or by any portion of the coding sequence so long as the desired activity or function is retained. Thus, a gene refers to a DNA or RNA, or portion thereof, that encodes a polypeptide or an RNA chain that has functional role to play in an organism. For the purpose of this disclosure, it may be considered that genes include regions that regulate the production of the gene product, whether or not such regulatory sequences are adjacent to coding and/or transcribed sequences. Accordingly, a gene includes, but is not necessarily limited to, promoter sequences, terminators, translational regulatory sequences such as ribosome binding sites and internal ribosome entry sites, enhancers, silencers, insulators, boundary elements, replication origins, matrix attachment sites, and locus control regions.

[0041] A cell has been genetically modified, transformed, or transfected by exogenous DNA, e.g., a recombinant expression vector, when such DNA has been introduced inside the cell. The presence of the exogenous DNA results in permanent or transient genetic change. The transforming DNA may or may not be integrated (covalently linked) into the genome of the cell. For example, the transforming DNA may be maintained on an episomal element such as a plasmid. With respect to eukaryotic cells, a stably transformed cell is one in which the transforming DNA has become integrated into a chromosome so that it is inherited by daughter cells through chromosome replication. This stability is demonstrated by the ability of the eukaryotic cell to establish cell lines or clones that comprise a population of daughter cells containing the transforming DNA. A clone is a population of cells derived from a single cell or common ancestor by mitosis. A cell line is a clone of a primary cell that is capable of stable growth in vitro for many generations.

[0042] The terms non-naturally occurring, engineered, and synthetic are used interchangeably and indicate the involvement of the hand of man. The terms, when referring to nucleic acid molecules or polypeptides mean that the nucleic acid molecule or the polypeptide is at least substantially free from at least one other component with which it is naturally associated in nature and as found in nature, and/or the nucleic acid molecule or the polypeptide is associated with at least one other component with which it is not naturally associated in nature and/or that there is one or more changes in nucleic acid or amino acid sequence as compared with such sequence as it is found in nature and/or that the nucleic acid or polypeptide sequence was generated de novo, e.g., not based on or derived from any naturally occurring sequence.

[0043] A vector or expression vector is a replicon, such as plasmid, phage, virus, or cosmid, to which another DNA segment, e.g., an insert, may be attached or incorporated so as to bring about the replication of the attached segment in a cell.

[0044] The term contacting as used herein refers to bring or put in contact, to be in or come into contact. The term contact as used herein refers to a state or condition of touching or of immediate or local proximity.

[0045] As used herein, the terms providing, administering, and introducing, are used interchangeably herein and refer to the placement of the composition or systems of the disclosure into a cell, organism, or subject by a method or route which results in at least partial localization to a desired site. The composition or systems can be administered by any appropriate route which results in delivery to a desired location in the cell, organism, or subject.

[0046] A subject or patient may be human or non-human and may include, for example, animal strains or species used as model systems for research purposes, such a mouse model as described herein. Likewise, a patient may include either adults or juveniles (e.g., children). Moreover, patient may mean any living organism, preferably a mammal (e.g., human or non-human) that may benefit from the administration of compositions contemplated herein. Examples of mammals include, but are not limited to, any member of the Mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents such as rats, mice, and guinea pigs, and the like. Examples of non-mammals include, but are not limited to, birds, fish, and the like. In one embodiment of the methods and compositions provided herein, the mammal is a human.

[0047] Preferred methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the present disclosure. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting.

Deaminases

[0048] Disclosed herein are synthetic deaminases. A deaminase catalyzes removal of an amino group from a compound or molecule (e.g., a nucleic acid/nucleotide or protein/amino acid). In some embodiments, the deaminase is an adenosine deaminase, also sometimes referred to as an adenine deaminase. Adenosine deaminases catalyze the deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. Accordingly, with repair and replication mechanisms adenosine deaminase can ultimately lead to the conversion of an A:T base pair to a G:C base pair.

[0049] In some embodiments, the deaminases comprise an amino acid sequence having at least 75% identity (e.g., at least 76%, at least 77%, at least 78%, at least 79%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) to any one of SEQ ID NOs: 1-23. In some embodiments, the deaminases comprise an amino acid sequence having at least 70% identity to any one of SEQ ID NOs: 24-776. In some embodiments, the deaminases comprise an amino acid sequence having at least 70% identity to any one of SEQ ID NOs: 1-776. In some embodiments, the deaminases comprise an amino acid sequence having any one of SEQ ID NOs: 1-776.

[0050] Any of the deaminases described herein may comprise one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or more, etc.) amino acid substitutions as compared to SEQ ID NOs: 1-776. An amino acid replacement or substitution refers to the replacement of one amino acid at a given position or residue by another amino acid at the same position or residue within a polypeptide sequence. Amino acids are broadly grouped as aromatic or aliphatic. An aromatic amino acid includes an aromatic ring. Examples of aromatic amino acids include histidine (H or His), phenylalanine (F or Phe), tyrosine (Y or Tyr), and tryptophan (W or Trp). Non-aromatic amino acids are broadly grouped as aliphatic. Examples of aliphatic amino acids include glycine (G or Gly), alanine (A or Ala), valine (V or Val), leucine (L or Leu), isoleucine (I or Ile), methionine (M or Met), serine (S or Ser), threonine (T or Thr), cysteine (C or Cys), proline (P or Pro), glutamic acid (E or Glu), aspartic acid (A or Asp), asparagine (N or Asn), glutamine (Q or Gin), lysine (K or Lys), and arginine (R or Arg).

[0051] The amino acid replacement or substitution can be conservative, semi-conservative, or non-conservative. The phrase conservative amino acid substitution or conservative mutation refers to the replacement of one amino acid by another amino acid with a common property. A functional way to define common properties between individual amino acids is to analyze the normalized frequencies of amino acid changes between corresponding proteins of homologous organisms (Schulz and Schirmer, Principles of Protein Structure, Springer-Verlag, New York (1979)). According to such analyses, groups of amino acids may be defined where amino acids within a group exchange preferentially with each other and therefore resemble each other most in their impact on the overall protein structure (Schulz and Schirmer). Examples of conservative amino acid substitutions include substitutions of amino acids within the sub-groups described above, for example, lysine for arginine and vice versa such that a positive charge may be maintained, glutamic acid for aspartic acid and vice versa such that a negative charge may be maintained, serine for threonine such that a free OH can be maintained, and glutamine for asparagine such that a free NH.sub.2 can be maintained. Semi-conservative mutations include amino acid substitutions of amino acids within the same groups listed above, but not within the same sub-group. For example, the substitution of aspartic acid for asparagine, or asparagine for lysine, involves amino acids within the same group, but different sub-groups. Non-conservative mutations involve amino acid substitutions between different groups, for example, lysine for tryptophan, or phenylalanine for serine, etc.

Fusion Proteins

[0052] The present disclosure also provides fusion proteins comprising one or more of the deaminases fused to a nucleic acid binding domain. The fusion proteins are not limited by orientation or directionality of the deaminase and the nucleic acid binding domain. For example, the nucleic acid binding domain may be fused to the N-terminus or C-terminus of the deaminase, in any orientation, e.g., N-terminus to N-terminus, C-terminus to C-terminus, N-terminus to C-terminus, or C-terminus to N-terminus.

[0053] Nucleic acid binding domains include polypeptides, proteins, or moieties which are capable of binding double-or single-stranded DNA, RNA, or combinations thereof, generally or with sequence specificity either alone or in coordination with another molecule. In some embodiments, the nucleic acid binding domain is capable of binding directly to the target nucleic acid sequences. In some embodiments, the nucleic acid binding domain is capable of binding indirectly to the target nucleic acid sequences, through an additional molecule. Exemplary nucleic acid binding domains include polypeptides having helix-turn-helix motifs, zinc fingers, leucine zippers, HMG-box (high mobility group box) domains, winged helix regions, winged helix-turn-helix regions, helix-loop-helix regions, immunoglobulin folds, B3 domains, Wor3 domains, TAL effector DNA-binding domains, and the like. The nucleic acid binding domain may be a natural binding domain. In some embodiments, the nucleic acid binding domain comprises a programmable nucleic acid binding domain, e.g., a nucleic acid binding domain engineered, for example by altering one or more amino acid of a natural nucleic acid binding domain, to bind to a predetermined nucleotide sequence.

[0054] The nucleic acid binding domain may be derived from domains found in naturally occurring transcription activator-like effectors (TALEs) such as AvrBs3, Hax2, Hax3 or Hax4 (Bonas et al. Mol Gen Genet 218(1):127-36, 1989; Kay et al. Mol Plant Microbe Interact 18(8): 838-48, 2005). TALEs have a modular binding domain consisting of repetitive sequences of residues; each repeat region consists of 34 amino acids. A pair of residues at the 12th and 13th position of each repeat region determines the nucleotide specificity and combining of the regions allows synthesis of sequence-specific TALE binding domains. In some embodiments, the TALE binding domains may be engineered using known methods to provide a binding domain with chosen specificity for any target sequence. The binding domain may comprise multiple (e.g., 2, 3, 4, 5, 6, 10, 20, or more) TALE effector binding motifs. In particular, any number of nucleotide-specific TALE effector motifs can be combined to form a sequence-specific binding domain to be employed in the fusion protein.

[0055] In some embodiments, the nucleic acid binding domain is derived from an RNA-guided protein (e.g., an RNA-guided nuclease). These proteins associate with an RNA molecule which guides the protein to the target DNA based on sequence complementarity of the RNA molecule to the target DNA. Exemplary RNA-guided proteins include for example, Cas proteins, transposon proteins (e.g., ISC transposon proteins or TnpB proteins, and other homologous proteins), and the Fanzor protein.

[0056] In some embodiments, the nucleic acid binding domain is derived from a Clustered Regularly Interspaced Short Palindromic Repeats associated (Cas) protein and associates with the target nucleic acid through a guide RNA (gRNA), a full description of which is provided elsewhere herein. The gRNA itself comprises a sequence complementary to one strand of the target sequence and a scaffold sequence binds and recruits the Cas protein to the target sequence. Thus, the disclosure provides base editors, which are fusion proteins of a Cas protein, generally a fully or partially catalytically inactivated Cas nuclease, as described below, and a deaminase or base editing enzyme.

[0057] The Cas protein can be from any Type or Class of CRISPR-Cas systems (e.g., Class 1, Class 2, Class 3, Types I-VI, or any subtypes thereof) from any species. Exemplary Cas proteins include: Cas1, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9, Cas10, Cas12, Cas13, and the like. In some embodiments, the Cas protein is Cas9 or Cas 12. Fragments or variants of any Cas protein which retain their nucleic acid binding capability may also be suitable for use as a nucleic acid binding domain in a fusion protein disclosed herein.

[0058] In some embodiments, the Cas protein is Cas9, or a fragment thereof. The Cas9 protein may be obtained from any suitable organism. For example, a number of bacteria express Cas9 protein orthologs or variants. Cas9 proteins of other species are known in the art (see, e.g., U.S. Patent Application Publication 2017/0051312, incorporated herein by reference) and may be used in connection with the present disclosure. The amino acid sequences of Cas proteins from a variety of species are publicly available through the GenBank, UniProt, and JGI Integrated Microbial Genomes and Microbiomes (IMG/M) databases. The Cas9 protein may be from Streptococcus pyogenes, Staphylococcus aureus (S. aureus), Campylobacter jejuni, Corynebacterium diphtheria, Eubacterium ventriosum, Streptococcus pasteurianus, Lactobacillus farciminis, Sphaerochaeta globus, Azospirillum (strain B510), Gluconacetobacter diazotrophicus, Neisseria cinerea, Roseburia intestinalis, Parvibaculum lavamentivorans, Nitratifractor salsuginis (strain DSM 16511), Campylobacter lari (strain CF89-12), or Streptococcus thermophilus (strain LMD-9). In some embodiments, the Cas9 is from Streptococcus pyogenes or Staphylococcus aureus.

[0059] Engineered Cas protein variants having one or more inactivated nuclease domains; alterations in the PAM requirements of target nucleic acids; decreased off-target binding or increased on-target binding; decreased editing windows on target nucleic acid; decreased bystander effects, editing of nucleotides outside but near editing window; and the like are suitable for use in the disclosed fusion proteins. For example, Streptococcus pyogenes Cas 9 (SpCas9) variants SpCas9-VQR, -VRQR, -EQR, -VRER, xCas9, SpCas9-NG, SpG, and SaKKHn allow targeting of genomic regions containing non-NGG PAMs and SpRY is a near-PAMless variant of SpCas9 (See, Kleinstiver B P et al., Nature. 523, 481-5 (2015); Kleinstiver B P et al., Nature. 529, 490-5 (2016); Kim et al., Nat. Biotechnol. 35, 371-376 (2017); Nishimasu, H. et al., Science 361, 1259-1262 (2018); Hu J H, et al., Nature. 556, 57-63 (2018); Miller, et al. Nat. Biotechnol. 38, 471-481(2020); Yang, L. et al., Protein Cell 9, 814-819 (2018); Walton, et al., Science 268, 290-296 (2020), incorporated herein by reference).

[0060] In some embodiments, the Cas9 protein is a Cas9 nickase (Cas9n). Wild-type Cas9 has two catalytic nuclease domains (HNH and RuvC) facilitating double-stranded DNA breaks. A Cas9 nickase protein is typically engineered through inactivating point mutation(s) in one of the catalytic nuclease domains causing Cas9 to nick or enzymatically break only one of the two DNA strands using the remaining active nuclease domain. Cas9 nickases are known in the art (see, e.g., U.S. Patent Application Publication 2017/0051312, incorporated herein by reference) and include, for example, Streptococcus pyogenes with point mutations at D10 or H840. In select embodiments, the Cas9 nickase is Streptococcus pyogenes Cas9n (D10A).

[0061] In some embodiments, the Cas9 protein is a catalytically dead Cas9. Catalytically dead Cas 9 (dCas9) can be obtained, for example, by introducing point mutations (e.g., substitutions, deletions, or additions) in the Cas9 molecule at the DNA-cleavage domain, e.g., the nuclease domain, the RuvC and/or HNH domain. Sec, e.g., Jinek et al., Science 337:816-21 (2012), incorporated by reference herein in its entirety. For example, introducing two point mutations in the RuvC and HNH domains reduces the Cas9 nuclease activity while retaining the Cas9 nucleic acid binding activity. For example, Streptococcus pyogenes Cas9 may be rendered catalytically dead by mutations of D10 and at least one of E762, H840, N854, N863, or D986, typically H840 and/or N863A (see, e.g., U.S. Patent Application Publication 2017/0051312, incorporated herein by reference). Mutations in corresponding orthologs are known, such as N580 in Staphylococcus aureus Cas9. Similar mutations can also apply to any other naturally occurring Cas9 (e.g., Cas9 from other species) or engineered Cas9 molecules. Oftentimes, such mutations result in the catalytically dead Cas9 possessing no more than 3% of the normal nuclease activity.

[0062] In some embodiments, the deaminase and the nucleic acid binding domain are covalently linked in a single amino acid chain through a linker. The linker may have any of a variety of amino acid sequences. Proteins can be joined by a linker polypeptide, generally of a flexible nature, although other chemical linkages are not excluded. Suitable linkers include polypeptides of between 1 amino acid and 100 amino acids in length, 4 amino acids and 40 amino acids in length, or between 4 amino acids and 25 amino acids in length. The linking peptides may have virtually any amino acid sequence, bearing in mind that the preferred linkers will have a sequence that results in a generally flexible peptide. Small amino acids, such as glycine and alanine, are useful in creating a flexible peptide linker. A variety of different linkers are considered suitable for use, including but not limited to, glycine-serine polymers, glycine-alanine polymers, and alanine-serine polymers. Such fusion proteins can be expressed recombinantly from a single nucleic acid encoding the amino acid chain.

[0063] Alternatively, the nucleic acid binding domain and the deaminase may be individually fused to one half of a binding pair (e.g., from a recruitment system) and, when introduced into the same system or location, the deaminase and nucleic acid binding domain form a protein conjugate through the recruitment system. The recruitment system can comprise any binding pair. For example, the recruitment system may comprise an aptamer and an aptamer binding protein. The recruitment system may be a so-called split system. Split systems include two or more polypeptide chains that reassemble into an operable fusion protein or protein conjugate upon association of the two binding partners. Split systems include, but are not limited to, intein, MS2, or SunTag based systems.

[0064] In some embodiments, the aptamer sequence is a nucleic acid (e.g., RNA aptamer) sequence. In some embodiments, the guide RNA also comprises a sequence of one or more RNA aptamers, or distinct RNA secondary structures or sequences that can recruit and bind another molecular species, an adaptor molecule, such as a nucleic acid or protein. Any RNA aptamer/aptamer binding protein pair known may be selected and used in connection with the present disclosure (see, e.g., Jayasena, S. D., Clinical Chemistry. 45(9): p. 1628-1650, (1999); Gelinas, et al., Current Opinion in Structural Biology 36: p. 122-132, (2016); and Hasegawa, H., Molecules, 21(4): p. 421 (2016), incorporated herein by reference).

[0065] In some embodiments, the aptamer sequence is a peptide aptamer sequence. In some embodiments, the nucleic acid binding domain comprises the peptide aptamer sequence and the deaminase comprises the peptide aptamer binding protein. In some embodiments, the deaminase comprises the peptide aptamer sequence and the nucleic acid binding domain comprises the peptide aptamer binding protein. The peptide aptamer sequence or peptide aptamer binding protein may be fused in any orientation (e.g., N-terminus to C-terminus, C-terminus to N-terminus, N-terminus to N-terminus). The peptide aptamer sequence or peptide aptamer binding protein may be fused by a linker region. Suitable linker regions are known in the art. The linker may be flexible or configured to allow the functionality and association with the DNA or other proteins with decreased steric hindrance. The linker sequences may provide an unstructured or linear region of the polypeptide, for example, with the inclusion of one or more glycine and/or serine residues. The linker sequences can be at least about 2, 3, 4, 5, 6, 7, 8, 9, 10 or more amino acids in length.

[0066] The peptide aptamers can be naturally occurring or synthetic peptides that are specifically recognized by an affinity agent. Such aptamers include, but are not limited to, a c-Myc affinity tag, an HA affinity tag, a His affinity tag, an S affinity tag, a methionine-His affinity tag, an RGD-His affinity tag, a 7 His tag, a FLAG octapeptide, a strep tag or strep tag II, a V5 tag, or a VSV-G epitope. Corresponding aptamer binding proteins are well-known in the art and include, for example, primary antibodies, biotin, affimers, single domain antibodies, and antibody mimetics.

[0067] Any of the deaminases and/or fusion proteins disclosed herein may further comprise one or more proteins, polypeptides (e.g., protein domain sequences), or peptides. For example, the deaminases and/or fusion proteins disclosed herein may be fused to another protein or protein domain that provides for tagging or visualization (e.g., GFP). The one or more proteins, polypeptides (e.g., protein domain sequences), or peptides may be appended at an N-terminus, a C-terminus, internally, or a combination thereof. The one or more proteins, polypeptides (e.g., protein domain sequences), or peptides may be fused in any orientation in relationship to the disclosed protein. The one or more proteins, polypeptides (e.g., protein domain sequences), or peptides may be fused via a linker, as described above.

[0068] In some embodiments, the deaminases and/or fusion proteins comprise one or more nuclear localization sequences (NLSs). The nuclear localization sequence may be appended, for example, to the N-terminus, a C-terminus, internally, or a combination thereof. In such cases when the deaminase and/or fusion protein comprises two or more NLSs, the NLSs may be in tandem, separated by a linker, at either end of the protein, or one or more may be embedded in the protein.

[0069] The nuclear localization sequence may comprise any amino acid sequence known in the art to functionally tag or direct a protein for import into a cell's nucleus (e.g., for nuclear transport). Usually, a nuclear localization sequence comprises one or more positively charged amino acids, such as lysine and arginine. The NLS may be appended by a linker.

[0070] In some embodiments, the NLS is a monopartite sequence. A monopartite NLS comprises a single cluster of positively charged or basic amino acids. In some embodiments, the monopartite NLS comprises a sequence of K-K/R-X-K/R, wherein X can be any amino acid. Exemplary monopartite NLS sequences include those from the SV40 large T-antigen, c-Myc, and TUS-proteins. In some embodiments, the NLS is a bipartite sequence. Bipartite NLSs comprise two clusters of basic amino acids, separated by a spacer of about 9-12 amino acids. Exemplary bipartite NLSs include the nuclear localization sequences of nucleoplasmin, EGL-12, or bipartite SV40. In some embodiments, the NLS comprises a sequence of: KR(K/R)R (SEQ ID NOs: 792-793); K(K/R)RK (SEQ ID NOs: 794-795); (R/P)XXKR(K/R)({circumflex over ()}DE) (SEQ ID NOS: 796-799) or (R/P)XXKR({circumflex over ()}DE) (K/R) (SEQ ID NOs: 800-803) wherein ({circumflex over ()}DE) represents any amino acid except for Asp or Glu; KRX(W/F/Y)XXAF (SEQ ID NOs: 804-806); LGKR(K/R)(W/F/Y) (SEQ ID NO: 807-808); or a bipartite sequence thereof.

[0071] The deaminases and/or fusion proteins may also comprise an epitope tag (e.g., 3xFLAG tag, an HA tag, a Myc tag, and the like). In some embodiments, the epitope tag may be adjacent, either upstream or downstream, to a nuclear localization sequence. The epitope tags may be at the N-terminus, a C-terminus, or a combination thereof of the corresponding protein or polypeptide.

[0072] In some embodiments, the deaminases and/or fusion proteins may be fused with one or more (e.g., two, three, four, or more) protein transduction moieties. A protein transduction moiety is a polypeptide, polynucleotide, carbohydrate, or organic or inorganic compound that facilitates traversing a lipid bilayer, micelle, cell membrane, organelle membrane, or vesicle membrane. A protein transduction moiety attached to another molecule facilitates the molecule traversing a membrane, for example going from extracellular space to intracellular space, or cytosol to within an organelle. The protein transduction moiety may be linked to the terminus of the deaminase or fusion protein, or alternatively be inserted internally. Examples of protein transduction moieties include but are not limited to a minimal undecapeptide protein transduction domain (corresponding to residues 47-57 of HIV-1 TAT comprising); a polyarginine sequence comprising a number of arginines sufficient to direct entry into a cell (e.g., 3, 4, 5, 6, 7, 8, 9, 10, or 10-50 arginines); a VP22 domain (Zender et al. (2002) Cancer Gene Ther. 9(6):489-96); a Drosophila Antennapedia protein transduction domain (Noguchi et al. (2003) Diabetes 52(7):1732-1737); a truncated human calcitonin peptide (Trehin et al. (2004) Pharm. Research 21:1248-1256); polylysine (Wender et al. (2000) Proc. Natl. Acad. Sci. USA 97:13003-13008); Transportan, and the like.

Systems and Compositions

[0073] Disclosed herein are systems and compositions that comprise a deaminase or a nucleic acid encoding thereof. In some embodiments, the systems and compositions comprise a deaminase and a nucleic acid binding polypeptide, or one or more nucleic acids encoding thereof. In some embodiments, the deaminase and the nucleic acid binding polypeptide are fused as a single protein, for example as described above for the fusion protein. In some embodiments, the deaminase and the nucleic acid binding polypeptide are each linked to a half of a binding pair. Descriptions of the deaminases, nucleic acid binding polypeptides, and fusion protein provided above are equally applicable to the systems and compositions.

[0074] In some embodiments, the nucleic acid sequences that encode the deaminase and the nucleic acid binding polypeptide are on the same nucleic acid. In some embodiments, the nucleic acid sequences that encode the deaminase and the nucleic acid binding polypeptide are on different nucleic acids. In some embodiments, the nucleic acids comprise one or more messenger RNAs, one or more vectors, or any combination thereof.

[0075] In some embodiments, for example when the nucleic acid binding polypeptide is an RNA-guided protein (e.g., a Cas protein) or fragment thereof, the compositions or systems further comprise at least one guide RNA (gRNA) or one or more nucleic acids comprising a sequence encoding the least one gRNA. In instances when the composition or system comprises more than one gRNA, each may be encoded on the same or different nucleic acid as the other gRNA, together or separate from either or both of the deaminase and the nucleic acid binding polypeptide. For example, the system and compositions may comprise a first nucleic acid encoding the deaminase and the nucleic acid binding polypeptide and a second nucleic acid encoding the gRNA; a first nucleic acid encoding the deaminase and the gRNA and a second nucleic acid encoding the nucleic acid binding polypeptide; a first nucleic acid encoding the deaminase and a second nucleic acid encoding the gRNA and the nucleic acid binding polypeptide; or a single nucleic acid encoding the deaminase, the nucleic acid binding polypeptide, and the gRNA. In some embodiments, the at least one gRNA is provided in a ribonucleoprotein (RNP) complex with the RNA-guided protein.

[0076] The gRNA may contain separate crRNA and tracrRNA sequences (or dual guide RNA) or having the crRNA and tracrRNA fused by a flexible linker (or single guide RNA, sgRNA). The terms gRNA, guide RNA, and guide sequence may be used interchangeably throughout and refer to a nucleic acid comprising a sequence that determines the sequence specificity of the CRISPR-associated protein. A gRNA hybridizes to (complementary to, partially or completely) a target nucleic acid sequence (e.g., the genome in a host cell).

[0077] In some embodiments, at least one gRNA is encoded in a CRISPR array. CRISPR arrays contain a series of direct repeats separated by short sequences called spacers. The CRISPR-associated protein described herein may have a preference for direct repeat sequences. These can be determined by methods known in the art. For example, the CRISPR RNA (crRNA) may contain multiple gRNAs or may contain more than one different sequence each configured to hybridize a distinct target nucleic acid sequence.

[0078] The gRNA or portion thereof that hybridizes to the target nucleic acid (a target site) may be between 15-40 nucleotides in length. gRNAs or sgRNA(s) used in the present disclosure can be between about 5 and 100 nucleotides long, or longer. The gRNA may be a non-naturally occurring or engineered gRNA.

[0079] To facilitate gRNA design, many computational tools have been developed (See Prykhozhij et al. (PLoS ONE, 10(3): (2015)); Zhu et al. (PLoS ONE, 9(9) (2014)); Xiao et al. (Bioinformatics. January 21 (2014)); Heigwer et al. (Nat Methods, 11(2): 122-123 (2014)). Methods and tools for guide RNA design are discussed by Zhu (Frontiers in Biology, 10 (4) pp. 289-296 (2015)), which is incorporated by reference herein. Additionally, there are many publicly available software tools that can be used to facilitate the design of sgRNA(s); including but not limited to, Genscript Interactive CRISPR gRNA Design Tool, WU-CRISPR, and Broad Institute GPP sgRNA Designer. There are also publicly available pre-designed gRNA sequences to target many genes and locations within the genomes of many species (human, mouse, rat, zebrafish, C. elegans), including but not limited to, IDT DNA Predesigned Alt-R CRISPR-Cas9 guide RNAs, Addgene Validated gRNA Target Sequences, and GenScript Genome-wide gRNA databases.

[0080] In some embodiments, the gRNA sequence that binds to the target nucleic acid may be fused to a scaffold sequence (e.g., tracrRNA). In some embodiments, such a chimeric gRNA may be referred to as a single guide RNA (sgRNA). Exemplary scaffold sequences will be evident to one of skill in the art and can be found, for example, in Jinek, et al. Science (2012) 337(6096):816-821, and Ran, et al. Nature Protocols (2013) 8:2281-2308, incorporated herein by reference in their entireties.

[0081] In some embodiments, the targeting gRNA sequence and tracrRNA scaffold sequence are expressed as separate transcripts. In some embodiments, this may be referred to as a dual guide RNA In such embodiments, the gRNA sequence further comprises an additional sequence that is complementary to a portion of the scaffold sequence and functions to bind (hybridize) the scaffold sequence.

[0082] Complementarity refers to the ability of a nucleic acid to form hydrogen bond(s) with another nucleic acid sequence by either traditional Watson-Crick or other non-traditional types. A percent complementarity indicates the percentage of residues in a nucleic acid molecule, which can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence. Full complementarity is not necessarily required, provided there is sufficient complementarity to cause hybridization. There may be mismatches distal from the PAM.

[0083] In some embodiments, the compositions and systems may further comprise one or more additional genome engineering tools. For example, the compositions may further comprise nucleases, such as zinc finger nucleases (ZFNs) and/or transcription activator like effector nucleases (TALENs); transcriptional activators, transcriptional repressors, histone-modifying proteins, integrases, recombinases, and the like.

[0084] The compositions or systems may further comprise an excipient or carrier. Excipients and carriers may include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents. Some examples of materials which can serve as excipients and/or carriers are sugars including, but not limited to, lactose, glucose and sucrose; starches including, but not limited to, corn starch and potato starch; cellulose and its derivatives including, but not limited to, sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients including, but not limited to, cocoa butter and suppository waxes; oils including, but not limited to, peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols; including propylene glycol; esters including, but not limited to, ethyl oleate and ethyl laurate; agar; buffering agents including, but not limited to, magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants including, but not limited to, sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants. The compositions of the present invention and methods for their preparation will be readily apparent to those skilled in the art. Techniques and formulations may be found, for example, in Remington's Pharmaceutical Sciences, 19th Edition (Mack Publishing Company, 1995).

[0085] In some embodiments, the excipient or carrier is pharmaceutically acceptable. Pharmaceutically acceptable carriers, including buffers, are well known in the art, and may comprise phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives; low molecular weight polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; amino acids; hydrophobic polymers; monosaccharides; disaccharides; and other carbohydrates; metal complexes; and/or non-ionic surfactants. Sec, e.g., Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K. E. Hoover.

[0086] The carrier may include a delivery vehicle. Delivery vehicles such as nanoparticle-and lipid-based delivery systems can be used. Exemplary delivery vehicles include, but are not limited to, microparticle compositions comprising a variety of polymers, liposomes or lipid nanoparticles, viral vectors, ribonucleoprotein (RNP) complexes, and the like.

[0087] Microparticles can include, but are not limited to, liposomes, nanoparticles, microspheres, nanospheres, microcapsules, and nanocapsules. In some cases, microparticle can include one or more of the following: a poly(lactide-co-glycolide), aliphatic polyesters including, but not limited to, poly-glycolic acid and poly-lactic acid, hyaluronic acid, modified polysaccharides, chitosan, cellulose, dextran, polyurethanes, polyacrylic acids, pseudo-poly(amino acids), polyhydroxybutyrate-related copolymers, polyanhydrides, polymethylmethacrylate, poly(ethylene oxide), lecithin, lipids, and phospholipids, in any combination thereof.

[0088] In some embodiments, a liposome or lipid nanoparticle encapsulates the disclosed systems, nucleic acids, or proteins (e.g., deaminases and nucleic acid binding polypeptides). Methods of making lipid compositions include, for example, lipid film hydration, optionally coupled with sonication or extrusion, solvent evaporation (e.g., ethanol injection, ether injection, or reverse phase evaporation), solvent-diffusion method, hot homogenization process, detergent removal methods, or combinations thereof. Any naturally occurring or synthetic vesicle forming lipid or combinations thereof can be used, including for example, di-aliphatic chain lipids, such as phospholipids; diglycerides; di-aliphatic glycolipids; single lipids such as sphingomyelin or glycosphingolipid; steroidal lipids; hydrophilic polymer derivatized lipids; or mixtures thereof. Liposome and lipid nanoparticle compositions of the disclosure may include one or more cationic and/or ionizable lipids, phospholipids, neutral or non-cationic lipids, polyethyleneglycol (PEG)-lipid conjugates, and/or sterols. In some embodiments, the lipid nanoparticle comprises a cationic lipid and/or ionizable lipid, a neutral or non-cationic lipid, and cholesterol.

[0089] The liposomes and lipid nanoparticles described herein may also include other components typically used in the formation of vesicles (e.g., for stabilization). Examples of such other components includes, without being limited thereto, fatty alcohols, fatty acids, and/or any other pharmaceutically acceptable excipients which may affect the surface charge, the membrane fluidity and assist in the incorporation of the lipid into the lipid assembly.

[0090] The liposome and lipid nanoparticle compositions of the disclosure can also be targeting compositions, e.g., contain one or more targeting moieties or biodistribution modifiers on the surface. A targeting moiety can be any agent that is capable of specifically binding or interacting with a desired target and are generally known in the art, for example ligands such as folic acid, proteins, antibody or antibody fragments, and the like).

[0091] The phrase pharmaceutically acceptable, as used in connection with the present disclosure, refers to molecular entities and other ingredients of such compositions that are physiologically tolerable and do not typically produce untoward reactions when administered to a subject (e.g., a mammal, a human). Preferably, as used herein, the term pharmaceutically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in mammals, and more particularly in humans. Acceptable means that the carrier is compatible with the composition (e.g., the nucleic acids, vectors, cells, proteins, or polypeptides) and does not negatively affect the subject to which the composition(s) are administered. Any of the compositions to be used in the present methods can comprise pharmaceutically acceptable carriers, excipients, or stabilizers in the form of lyophilized formations or aqueous solutions.

Nucleic Acids

[0092] Also disclosed herein are nucleic acids encoding the deaminases or fusion proteins as described herein. The nucleic acids may be DNA, RNA, or combinations thereof. In some embodiments, the nucleic acids comprise one or more messenger RNAs, one or more vectors, or any combination thereof.

[0093] In certain embodiments, the nucleic acids are engineered for codon-optimization. It will be appreciated altering codons to those most frequently used in the cells or subject of interest allows for maximum expression. Such modified nucleic acid sequences are commonly described in the art as codon-optimized. In some embodiments, the nucleic acid sequence is considered codon-optimized if at least about 60% (e.g., about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 98%) of the codons encoded therein are preferred codons to the subject of interest.

[0094] The present disclosure also provides for DNA segments encoding the deaminases or fusion proteins disclosed herein, vectors containing these segments, and cells containing the vectors. The vectors may be used to propagate the DNA segment in an appropriate cell and/or to allow expression from the segment (e.g., an expression vector). The person of ordinary skill in the art would be aware of the various vectors available for propagation and expression of a nucleic acid sequence.

[0095] The present disclosure further provides engineered, non-naturally occurring vectors and vector systems, which can encode the deaminases, fusion proteins, or one or more or all of the components of the systems or compositions, as disclosed herein. The vector(s) can be introduced into a cell that is capable of expressing the polypeptide encoded thereby, including any suitable prokaryotic or eukaryotic cell.

[0096] The vectors of the present disclosure may be delivered to a eukaryotic cell. Modification of the eukaryotic cells via the present system can take place in a cell culture, where the method comprises isolating the eukaryotic cell from a subject prior to the modification. In some embodiments, the method further comprises returning said eukaryotic cell and/or cells derived therefrom to the subject.

[0097] Viral and non-viral based gene transfer methods can be used to introduce nucleic acids encoding components of the present system into cells, tissues, or a subject. Such methods can be used to administer nucleic acids encoding components of the present system to cells in culture, or in a host organism. Non-viral vector delivery systems include DNA plasmids, cosmids, RNA (e.g., a transcript of a vector described herein), nucleic acids, and nucleic acids complexed with a delivery vehicle. Viral vector delivery systems include DNA and RNA viruses, which have either episomal or integrated genomes after delivery to the cell. Viral vectors include, for example, retroviral, lentiviral, adenoviral, adeno-associated and herpes simplex viral vectors.

[0098] In certain embodiments, plasmids that are non-replicative, or plasmids that can be cured by high temperature may be used, such that any or all of the necessary components of the system may be removed from the cells under certain conditions. For example, this may allow for DNA integration by transforming bacteria of interest, but then being left with engineered strains that have no memory of the plasmids or vectors used for the integration.

[0099] Drug selection strategies may be adopted by positively selecting for cells that underwent DNA integration. A donor nucleic acid may contain one or more drug-selectable markers within the cargo. Then presuming that the original donor plasmid is removed, drug selection may be used to enrich for integrated clones. Colony screenings may be used to isolate clonal events.

[0100] A variety of viral constructs may be used to deliver deaminases, fusion proteins, or one or more or all of the components of the system or compositions (such as a deaminase, fusion protein, and/or a guide RNA) to the targeted cells and/or a subject. Nonlimiting examples of such recombinant viruses include recombinant adeno-associated virus (AAV), recombinant adenoviruses, recombinant lentiviruses, recombinant retroviruses, recombinant herpes simplex viruses, recombinant poxviruses, phages, etc. The present disclosure provides vectors capable of integration in the host genome, such as retrovirus or lentivirus. See, e.g., Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons, New York, 1989; Kay, M. A., et al., 2001 Nat. Medic. 7(1):33-40; and Walther W. and Stein U., 2000 Drugs, 60(2): 249-71, incorporated herein by reference.

[0101] In one embodiment, a DNA segment encoding deaminases, fusion proteins, or one or more or all of the components of the system or compositions is contained in a plasmid vector that allows expression of the protein(s) and subsequent isolation and purification produced by the recombinant vector. Accordingly, the proteins disclosed herein can be purified following expression, obtained by chemical synthesis, or obtained by recombinant methods.

[0102] To construct cells that express the deaminases, fusion proteins, or one or more or all of the components of the system or compositions, expression vectors for stable or transient expression may be constructed via conventional methods as described herein and introduced into cells. For example, nucleic acids encoding the deaminases, fusion proteins, or one or more or all of the components of the system or compositions may be cloned into a suitable expression vector, such as a plasmid or a viral vector in operable linkage to a suitable promoter. The selection of expression vectors/plasmids/viral vectors should be suitable for integration and replication in eukaryotic cells.

[0103] In certain embodiments, vectors of the present disclosure can drive the expression of one or more sequences in prokaryotic cells. Promoters that may be used include T7 RNA polymerase promoters, constitutive E. coli promoters, and promoters that could be broadly recognized by transcriptional machinery in a wide range of bacterial organisms. The system may be used with various bacterial hosts.

[0104] In certain embodiments, vectors of the present disclosure can drive the expression of one or more sequences in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, Nature (1987) 329:840, incorporated herein by reference) and pMT2PC (Kaufman, et al., EMBO J. (1987) 6:187, incorporated herein by reference). When used in mammalian cells, the expression vector's control functions are typically provided by one or more regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, simian virus 40, and others disclosed herein and known in the art. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd eds., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989, incorporated herein by reference.

[0105] Vectors of the present disclosure can comprise any of a number of promoters known to the art, wherein the promoter is constitutive, regulatable or inducible, cell type specific, tissue-specific, or species specific. In addition to the sequence sufficient to direct transcription, a promoter sequence of the invention can also include sequences of other regulatory elements that are involved in modulating transcription (e.g., enhancers, Kozak sequences and introns). Many promoter/regulatory sequences useful for driving constitutive expression of a gene are available in the art and include, but are not limited to, for example, CMV (cytomegalovirus promoter), EF1a (human elongation factor 1 alpha promoter), SV40 (simian vacuolating virus 40 promoter), PGK (mammalian phosphoglycerate kinase promoter), Ubc (human ubiquitin C promoter), human beta-actin promoter, rodent beta-actin promoter, CBh (chicken beta-actin promoter), CAG (hybrid promoter contains CMV enhancer, chicken beta actin promoter, and rabbit beta-globin splice acceptor), TRE (Tetracycline response element promoter), Hl (human polymerase III RNA promoter), U6 (human U6 small nuclear promoter), and the like. Additional promoters that can be used for expression of the components of the present system, include, without limitation, cytomegalovirus (CMV) intermediate early promoter, a viral LTR such as the Rous sarcoma virus LTR, HIV-LTR, HTLV-1 LTR, Maloney murine leukemia virus (MMLV) LTR, mycoloproliferative sarcoma virus (MPSV) LTR, spleen focus-forming virus (SFFV) LTR, the simian virus 40 (SV40) early promoter, herpes simplex tk virus promoter, elongation factor 1-alpha (EF1-) promoter with or without the EF1- intron. Additional promoters include any constitutively active promoter. Alternatively, any regulatable promoter may be used, such that its expression can be modulated within a cell.

[0106] Moreover, inducible and tissue specific expression can be accomplished by placing the nucleic acid encoding such a molecule under the control of an inducible or tissue specific promoter/regulatory sequence. Examples of tissue specific or inducible promoter/regulatory sequences which are useful for this purpose include, but are not limited to, the rhodopsin promoter, the MMTV LTR inducible promoter, the SV40 late enhancer/promoter, synapsin 1 promoter, ET hepatocyte promoter, GS glutamine synthase promoter and many others. In addition, promoters which are well known in the art can be induced in response to inducing agents such as metals, glucocorticoids, tetracycline, hormones, and the like, are also contemplated for use with the invention. Thus, it will be appreciated that the present disclosure includes the use of any promoter/regulatory sequence capable of driving expression of the desired protein operably linked thereto.

[0107] The vectors of the present disclosure may direct expression of the nucleic acid in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Such regulatory elements include promoters that may be tissue specific or cell specific. The term tissue specific as it applies to a promoter refers to a promoter that is capable of directing selective expression of a nucleotide sequence of interest to a specific type of tissue (e.g., seeds) in the relative absence of expression of the same nucleotide sequence of interest in a different type of tissue. The term cell type specific as applied to a promoter refers to a promoter that is capable of directing selective expression of a nucleotide sequence of interest in a specific type of cell in the relative absence of expression of the same nucleotide sequence of interest in a different type of cell within the same tissue. The term cell type specific when applied to a promoter also means a promoter capable of promoting selective expression of a nucleotide sequence of interest in a region within a single tissue. Cell type specificity of a promoter may be assessed using methods well known in the art, e.g., immunohistochemical staining.

[0108] Additionally, the vector may contain, for example, some or all of the following: a selectable marker gene, such as the neomycin gene for selection of stable or transient transfectants in host cells; enhancer/promoter sequences from the immediate early gene of human CMV for high levels of transcription; transcription termination and RNA processing signals from SV40 for mRNA stability; 5- and 3-untranslated regions for mRNA stability and translation efficiency from highly-expressed genes like -globin or -globin; SV40 polyoma origins of replication and ColE1 for proper episomal replication; internal ribosome binding sites (IRESes), versatile multiple cloning sites; T7 and SP6 RNA promoters for in vitro transcription of sense and antisense RNA; a suicide switch or suicide gene which when triggered causes cells carrying the vector to die (e.g., HSV thymidine kinase, an inducible caspase such as iCasp9), and reporter gene for assessing expression of the chimeric receptor. Suitable vectors and methods for producing vectors containing transgenes are well known and available in the art. Selectable markers also include chloramphenicol resistance, tetracycline resistance, spectinomycin resistance, streptomycin resistance, erythromycin resistance, rifampicin resistance, bleomycin resistance, thermally adapted kanamycin resistance, gentamycin resistance, hygromycin resistance, trimethoprim resistance, dihydrofolate reductase (DHFR), GPT; the URA3, HIS4, LEU2, and TRPI genes of S. cerevisiae.

[0109] When introduced into the cell, the vectors may be maintained as an autonomously replicating sequence or extrachromosomal element or may be integrated into host DNA.

[0110] The proteins, polynucleotides encoding these proteins, and systems and compositions comprising the proteins and/or polynucleotides described herein may be delivered by any suitable means. In certain embodiments, the delivery is in vivo. In other embodiments, the delivery is to isolated/cultured cells (e.g., autologous iPS cells) in vitro to provide modified cells useful for in vivo delivery to patients afflicted with a disease or condition.

[0111] Vectors according to the present disclosure can be transformed, transfected, or otherwise introduced into a wide variety of cells. Transfection refers to the taking up of a vector by a cell whether or not any coding sequences are in fact expressed. Numerous methods of transfection are known to the ordinarily skilled artisan, for example, lipofectamine, calcium phosphate co-precipitation, electroporation, DEAE-dextran treatment, microinjection, viral infection, and other methods known in the art. Transduction refers to entry of a virus into the cell and expression (e.g., transcription and/or translation) of sequences delivered by the viral vector genome. In the case of a recombinant vector, transduction generally refers to entry of the recombinant viral vector into the cell and expression of a nucleic acid of interest delivered by the vector genome.

[0112] Any of the vectors comprising a nucleic acid sequence that encodes the deaminases, fusion proteins, or one or more or all of the components of the system or compositions is also within the scope of the present disclosure. Such a vector may be delivered into host cells by a suitable method. Methods of delivering vectors to cells are well known in the art and may include DNA or RNA electroporation, transfection reagents such as liposomes or nanoparticles to delivery DNA or RNA; delivery of DNA, RNA, or protein by mechanical deformation (see, e.g., Sharei et al. Proc. Natl. Acad. Sci. USA 110(6): 2082-2087 (2013) incorporated herein by reference); or viral transduction. In some embodiments, the vectors are delivered to host cells by viral transduction. Nucleic acids can be delivered as part of a larger construct, such as a plasmid or viral vector, or directly, e.g., by electroporation, lipid vesicles, viral transporters, microinjection, and biolistics (high-speed particle bombardment). Similarly, the construct containing the one or more transgenes can be delivered by any method appropriate for introducing nucleic acids into a cell. In some embodiments, the construct or the nucleic acid encoding the components of the present system is a DNA molecule. In some embodiments, the nucleic acid encoding the components of the present system is a DNA vector and may be electroporated to cells. In some embodiments, the nucleic acid encoding the components of the present system is an RNA molecule, which may be electroporated to cells.

[0113] Additionally, delivery vehicles such as nanoparticle-and lipid-based mRNA or protein delivery systems can be used. Further examples of delivery vehicles include lentiviral vectors, ribonucleoprotein (RNP) complexes, lipid-based delivery system, gene gun, hydrodynamic, electroporation or nucleofection microinjection, and biolistics. Various gene delivery methods are discussed in detail by Nayerossadat et al. (Adv Biomed Res. 2012; 1:27) and Ibraheem et al. (Int J Pharm. 2014 Jan. 1; 459(1-2):70-83), incorporated herein by reference.

[0114] In some embodiments, the deaminases, fusion proteins, or one or more or all of the components of the system or compositions may be mixed, individually or in any combination, with a carrier which are also within the scope of the present disclosure. Exemplary carriers include buffers, antioxidants, preservatives, carbohydrates, surfactants, and the like, and are described in detail elsewhere herein.

[0115] Also disclosed is a cell comprising the deaminases, fusion proteins, nucleic acids, or one or more or all of the components of the system or compositions described herein. In some embodiments, the cell is a prokaryotic cell. In some embodiments, the cell is a eukaryotic cell. In some embodiments, the cell is a mammalian cell. In some embodiments, the cell is a human cell.

Methods

[0116] The disclosure also provides methods of modifying a target nucleic acid sequence (e.g., DNA or RNA). The phrase modifying a nucleic acid sequence, as used herein, refers to modifying at least one physical feature of a nucleic acid sequence of interest. In some embodiments, the modifications comprise base editing. In some embodiments, the base editing edits an adenine in the target nucleic acid.

[0117] The methods comprise contacting a target nucleic acid sequence with a deaminase, fusion protein, composition, or system as described herein. In some embodiments, contacting a target nucleic acid sequence comprises introducing the deaminase, fusion protein, composition, or system into the cell. The deaminase, fusion protein, composition, or system may be introduced into eukaryotic or prokaryotic cells by methods known in the art, as described elsewhere herein.

[0118] The cell may be a prokaryotic cell, a plant cell, an insect cell, a vertebrate cell, an invertebrate cell, an animal cell, a mammalian cell, or a human cell. In some embodiments, the cell is a stem cell.

[0119] In some embodiments, the cell is ex vivo (e.g., fresh isolateearly passage). In some cases, the cell is in vivo. In some cases, the cell is in culture or in vitro (e.g., immortalized cell line). Cells may be from established cell lines or they may be primary cells, where primary cells, primary cell lines, and primary cultures are used interchangeably herein to refer to cells and cells cultures that have been derived from a subject and allowed to grow in vitro for a limited number of passages of the culture. For example, primary cultures are cultures that may have been passaged 0 times, 1 time, 2 times, 4 times, 5 times, 10 times, or 15 times, but not enough times go through the crisis stage. Typically, the primary cell lines are maintained for fewer than 10 passages in culture.

[0120] In some embodiments, introducing the deaminase, fusion protein, composition, or system into a cell comprises administering the deaminase, fusion protein, composition, or system to a subject. In some embodiments, the subject is human. The administering may comprise in vivo administration of the deaminase, fusion protein, composition, system, or a nucleic acid encoding the deaminase, fusion protein, or system. In alternative embodiments, an in vitro or ex vivo treated cell is transplanted into a subject.

[0121] In some embodiments, the target nucleic acid is a nucleic acid endogenous to a target cell. In some embodiments, the target nucleic acid is a genomic DNA sequence. The term genomic, as used herein, refers to a nucleic acid sequence (e.g., a gene or locus) that is located on a chromosome in a cell.

[0122] In some embodiments, the target nucleic acid encodes a gene or gene product. The term gene product, as used herein, refers to any biochemical product resulting from expression of a gene. Gene products may be RNA or protein. RNA gene products include non-coding RNA, such as tRNA, rRNA, microRNA (miRNA), and small interfering RNA (siRNA), and coding RNA, such as messenger RNA (mRNA). In some embodiments, the target nucleic acid sequence encodes a protein or polypeptide.

[0123] In some embodiments, the methods described herein result in an adenine (A) to guanine (G) point mutation within a gene (e.g., a coding region or non-coding region (e.g., a promoter or regulatory sequences) of a gene).

[0124] In some embodiments, the methods described herein alter the regulatory sequence of a gene (e.g., a gene promoter or gene repressor). Accordingly, in some embodiments, the methods described herein lead to modulation (increase, decrease, or cessation) of transcription of a gene. In some embodiments, the methods described herein alter the splicing of a gene (e.g., introduce or remove a splice site). Accordingly, in some embodiments, the method results in the introduction of a splice site in a gene. In alternative embodiments, the method results in the removal of a splice site.

[0125] In some embodiments, the methods described herein alter the coding sequence of a gene. In some embodiments, the alteration is silent or synonymous. In some embodiments, the alteration is non-synonymous and results in an amino-acid change. In some embodiments, the methods described herein generate a stop codon, for example, a premature stop codon within the coding region of a gene. In some embodiments, the methods described herein eliminate a stop codon, e.g., a stop codon in a target nucleic acid comprising the nucleic acid sequence TAG, TAA, or TGA.

[0126] In some embodiments, the methods described herein may be used to correct one or more defects or mutations in one or more genes (referred to as gene correction). In some cases, the target sequence encodes a defective version of a gene, and the disclosed systems and compositions are configured to correct, or ablate e.g., by mutating the start codon (ATG) and abolishing gene expression, the defective version of the gene. Alternatively, the target sequence may encode the wild-type version of the gene, and the disclosed systems and compositions are configured to confer the disease-causing mutation to the gene, for example, for use in cell and organismal models of the disease or disorder.

[0127] In some embodiments, the defective version of the gene includes a point mutation. Point mutations are the largest class of known pathogenic genetic variants and approximately half of which result from a change of a G-C to an A-T base pair. The deaminases and fusion proteins (e.g., base editors) disclosed herein may install or reverse point mutations, thereby providing methods for the study and treatment of disease-associated point mutations.

[0128] The present methods may be used in various bacterial hosts, including human pathogens that are medically important, and bacterial pests that are key targets within the agricultural industry, as well as antibiotic resistant versions thereof. The method may be designed to target any gene or any set of genes, such as virulence or metabolic genes, for clinical and industrial applications in other embodiments. The present methods may be used to inactivate microbial genes. In some embodiments, the gene is an antibiotic resistance gene. The present methods may be used to treat a multi-drug resistance bacterial infection in a subject. The present methods may also be used for genomic engineering within complex bacterial consortia.

[0129] The methods described here also provide for treating a disease or disorder in a subject. The method may comprise administering to the subject, in vivo, an effective amount of the deaminase, fusion protein, composition, or system, or by transplantation of ex vivo treated cells. A subject or patient may be human or non-human and may include, for example, animal strains or species used as model systems for research purposes, such a mouse model as described herein. Within the context of the present disclosure, the term effective amount refers to that quantity such that modification of the target nucleic acid is achieved.

[0130] In some embodiments, the systems and methods target one or more disease-associated genes. The term disease-associated gene, refers to any gene or polynucleotide whose gene products are expressed at an abnormal level or in an abnormal form in cells obtained from a disease-affected individual as compared with tissues or cells obtained from an individual not affected by the disease. A disease-associated gene may refer to a gene, the mutation or genetic variation of which is directly responsible or is in linkage disequilibrium with a gene(s) that is responsible for the etiology of a disease. In another embodiment, the target genomic DNA sequence can comprise a gene, the mutation of which contributes to a particular disease in combination with mutations in other genes.

[0131] In some embodiments, the one or more disease-associated gene comprises one or more point mutations, single nucleotide variants (SNVs), or single-nucleotide polymorphisms (SNPs). In some embodiments, the point mutation, SNV, or SNP comprises a mutation of a wild-type base to an adenine. In some embodiments, the point mutation, SNV, or SNP comprises a G to A point mutation. Accordingly, correction of the G to A point mutation, SNV, or SNP with the deaminases or fusion proteins disclosed herein results in a reversion to wild-type or non-disease-associated sequence. In some embodiments, the point mutation, SNV, or SNP comprises a C to T point mutation. Accordingly, correction of the A which base pairs with the T mutation results in a wild-type or non-disease-associated sequence following cellular replication/repair processes. Exemplary diseases associated with a point mutation, SNV, or SNP that may be treated with the disclosed methods include, but are not limited to, proliferative diseases, metabolic diseases, and lysosomal storage diseases.

[0132] When utilized as a method of treatment, the effective amount may depend on the particular condition being treated, the severity of the condition, the individual patient parameters including age, physical condition, size, gender and weight, the duration of the treatment, the nature of concurrent therapy (if any), the specific route of administration and like factors within the knowledge and expertise of the health practitioner. In some embodiments, the effective amount alleviates, relieves, ameliorates, improves, reduces the symptoms, or delays the progression of any disease or disorder in the subject. In some embodiments, the subject is a human.

[0133] A wide range of additional therapies may be used in conjunction with the methods of the present disclosure. The additional therapy may be administration of a therapeutic agent or may be an additional therapy not connected to administration of a therapeutic agent. Such additional therapies include, but are not limited to, surgery, immunotherapy, radiotherapy. The additional therapy may be administered at the same time as the above methods. In some embodiments, the additional therapy may precede or follow the treatment of the disclosed methods by time intervals ranging from hours to months.

[0134] In some embodiments, effective combination therapy is achieved with a single composition or pharmacological formulation or with two distinct compositions or formulations, administered at the same time or separated by a time interval. The therapeutic agent may comprise any manner of therapeutic, including protein, small molecule, nucleic acids, and the like. For example, therapeutic agents include, but are not limited to, immune modulators, chemotherapeutic agents, a nucleic acid (e.g., mRNA, aptamers, antisense oligonucleotides, ribozyme nucleic acids, interfering RNAs, antigene nucleic acids), decongestants, steroids, analgesics, antimicrobial agents, immunotherapies, or any combination thereof.

[0135] In the context of the present disclosure insofar as it relates to any of the disease conditions recited herein, the terms treat, treatment, and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition. Within the meaning of the present disclosure, the term treat also denotes to arrest, delay the onset (e.g., the period prior to clinical manifestation of a disease) and/or reduce the risk of developing or worsening a disease. For example, in connection with cancer the term treat may mean elimination or reduction of a patient's tumor burden, or prevention, delay, or inhibition of metastasis, etc.

[0136] The methods disclosed herein are also applicable to plants. For example, the methods can be used to generate novel engineered plants to improve agronomic traits, for example, herbicidal resistance, resistance to environmental stress, resistance to pests, etc.

[0137] The disclosed deaminases, fusion proteins, compositions, and systems can be introduced into a plant, or a plant cell, seed, fruit, plant part, or propagation material of the plant. The term plant propagation material refers to generative parts of a plant, which can be used for the multiplication of the plant, and vegetative plant material such as cuttings and tubers (e.g., potatoes). In some embodiments, the propagation material is a root, a corm, a tuber, a bulb, a slip, a cutting of the plant, and a rhizome. Parts of a plant are any sections of a plant (e.g., roots, cotyledons, tendrils, leaves, flowers, seeds, stems, callus tissue, nuts, and fruit) that develop from a plant propagation material or grow at a later time. The methods described herein can be used on any plant part. Examples of plant parts include but are not limited to the root, corm, tuber, bulb, slip and rhizome.

[0138] Methods of introducing exogenous nucleic acids into plant cells are well known in the art. Such plant cells are considered transformed. DNA constructs can be introduced into plant cells by various methods, including, but not limited to PEG-or electroporation-mediated protoplast transformation, tissue culture or plant tissue transformation by biolistic bombardment, or the Agrobacterium-mediated transient and stable transformation.

[0139] The transformation can be a transient or a stable transformation. As used herein, the term stable transformation is intended to mean that the nucleotide construct introduced into a plant integrates into the genome of the plant and is capable of being inherited by the progeny thereof Transient transformation is intended to mean that a polynucleotide is introduced into the plant and does not integrate into the genome of the plant or a polypeptide is introduced into a plant. In select embodiments, the nucleic acid encoding the RNA hairpin may be stably integrated into the plant genome, for example via Agrobacterium-mediated transformation.

[0140] Suitable methods also include viral infection (such as double stranded DNA viruses), transfection, conjugation, protoplast fusion, electroporation, particle gun technology, calcium phosphate precipitation, direct microinjection, silicon carbide whiskers technology, Agrobacterium-mediated transformation, and the like. The choice of method is generally dependent on the type of cell being transformed and the circumstances under which the transformation is taking place (e.g., in vitro, ex vivo, or in vivo). Transformation methods based upon the soil bacterium Agrobacterium tumefaciens are useful for introducing an exogenous nucleic acid molecule into a vascular plant. The wild-type form of Agrobacterium contains a Ti (tumor-inducing) plasmid that directs production of tumorigenic crown gall growth on host plants. Transfer of the tumor-inducing T-DNA region of the Ti plasmid to a plant genome requires the Ti plasmid-encoded virulence genes as well as T-DNA borders, which are a set of direct DNA repeats that delineate the region to be transferred. An Agrobacterium-based vector is a modified form of a Ti plasmid, in which the tumor inducing functions are replaced by the nucleic acid sequence of interest to be introduced into the plant host.

[0141] Agrobacterium-mediated transformation generally employs cointegrate vectors or binary vector systems, in which the components of the Ti plasmid are divided between a helper vector, which resides permanently in the Agrobacterium host and carries the virulence genes, and a shuttle vector, which contains the gene of interest bounded by T-DNA sequences. A variety of binary vectors are well known in the art and are commercially available, for example, from Clontech (Palo Alto, Calif.). Methods of co-culturing Agrobacterium with cultured plant cells or wounded tissue such as leaf tissue, root explants, hypocotyledons, stem pieces or tubers, for example, also are well known in the art. Sec., e.g., Glick and Thompson, (eds.), Methods in Plant Molecular Biology and Biotechnology, Boca Raton, Fla.: CRC Press (1993), incorporated herein by reference.

[0142] Microprojectile-mediated transformation also can be used. This method, first described by Klein et al. (Nature 327:70-73 (1987), incorporated herein by reference), relies on microprojectiles such as gold or tungsten that are coated with the desired nucleic acid molecule by precipitation with calcium chloride, spermidine, or polyethylene glycol. The microprojectile particles are accelerated at high speed into an angiosperm tissue using a device such as the BIOLISTIC PD-1000 (Biorad; Hercules Calif.).

[0143] As such, the disclosure also provides plants and plant propagation materials (e.g., plant cell, seed, fruit, or plant parts) produced using the methods disclosed herein. Genetically modified, transformed or transgenic plants include a plant into which an exogenous polynucleotide, e.g., a polynucleotide encoding the deaminase or fusion protein disclosed herein, has been introduced.

[0144] The methods disclosed herein are suitable for use with any plant, for example, grain crops, fruit crops, forage crops, root vegetable crops, leafy vegetable crops, flowering plants, conifers, trees, oil crops, plants used in phytoremediation, industrial crops, medicinal crops, laboratory model plants, and the like. As such, non-limiting examples of plants that may be used with the present methods include: grains, forage crops, fruits, vegetables, oil seed crops, palms, forestry, vines, maize (corn, Zea mays), banana, peanut, field peas, sunflower, tomato, canola, tobacco, wheat, barley, oats, potato, soybeans, cotton, carnations, sorghum, lupin, rice, rutabaga, celery, switchgrass, apple, petunias, Arabidopsis thaliana, Medicago truncatula, Medicago sativa, Brachypodium distachyon, Nicotiana benthamiana, or Setaria viridis.

[0145] Additionally, the disclosed methods can also be used as a synthetic biology tool to record cellular signaling and exposure to stimuli. The disclosed deaminases and fusion proteins can generate predictable single point mutations and by coupling the stimulus of interest to the activity or expression of the deaminase or fusion protein, the resulting stimulus-dependent single point mutations can be used to record exposure to signals into the genome. Accordingly, the methods may further comprise exposing the cell, subject, or plant, to stimulus of interest, wherein the deaminase or fusion protein is configured for activation to the stimulus of interest (e.g., transcriptionally or translationally controlled activation).

Kits

[0146] Also within the scope of the present disclosure are kits that include the deaminases, fusion proteins, nucleic acids, cells, compositions, systems, or components thereof as disclosed herein.

[0147] The kits may contain one or more reagents or other components useful, necessary, or sufficient for practicing any of the methods described herein, such as, transfection or administration reagents, negative and positive control samples (e.g., cells, template DNA), cells, containers housing one or more components (e.g., microcentrifuge tubes, boxes), detectable labels, detection and analysis instruments, software, instructions, and the like.

[0148] The kit may include instructions for use in any of the methods described herein. Kits optionally may provide additional components such as buffers and interpretive information. Normally, the kit comprises a container and a label or package insert(s) on or associated with the container. Instructions supplied in the kits of the disclosure are typically written instructions on a label or package insert. In some embodiment, the disclosure provides articles of manufacture comprising contents of the kits described above.

[0149] The kits provided herein are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging, and the like. A kit may have a sterile access port (for example, the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The container may also have a sterile access port.

[0150] The packaging may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses.

[0151] The kit will typically be provided with its various components in one or more packages, e.g., a fiber-based, a cardboard, a polymeric, or a Styrofoam box. The enclosure(s) can be configured so as to maintain a temperature differential between the interior and the exterior, for example, to provide insulating properties to keep the reagents at a preselected temperature for a preselected time. The packaging can be air-tight, waterproof (e.g., impermeable to changes in moisture or evaporation), and/or light-tight.

EXAMPLES

[0152] The following are examples of the present invention and are not to be construed as limiting.

Materials and Methods

Cell Culture, Plasmid Construction, and Transient Transfection

[0153] HEK293T cells (ATCC) were cultured at 37 C. and 5% (v/v) CO.sub.2 in high glucose DMEM with 4 mM L-glutamine, 1 mM sodium pyruvate and phenol red pH indicator (Gibco), supplemented with 10% FBS and 1 penicillin-streptomycin. 24 hours prior to transfection, cells were seeded at a density of 10.sup.3 cells/well in 96 well tissue culture-treated plates.

[0154] guide RNAs (gRNA) were cloned into pGuide plasmid with a U6 promoter driving their expression and a CMV-driven GFP transfection reporter using HiFi DNA Assembly protocols (New England Biolabs). Deaminase enzyme constructs, e.g., deaminases linked to Cas9n (nickase (D10A)), in pTwist CMV were purchased from Twist Bioscience, or a nickase version of OpenCRISPR-1 (Ruffolo, et al., bioRxiv 2024.04.22.590591).

[0155] For each transfection well, 50 ng of gRNA plasmid and 50 ng of deaminase enzyme plasmid were added to 5 L of Opti-MEM (Gibco). One non-targeting guide RNA negative control was included for each experiment. 0.2 L of TransIT-2020 transfection reagent (Mirus Bio) was diluted into 4 L of Opti-MEM. Plasmid and TransIT-2020 mixtures were combined, incubated for 15-30 min at room temperature, and added to HEK293T cells in a dropwise manner. Plates were gently rocked to mix and incubated for 72 hours. Guide RNA sequences are listed in Table 1.

Microscopy, Sample Preparation, and Sequencing

[0156] 72 hours post-transfection, qualitative assessments of transfection efficiency and cell health were made using fluorescence and brightfield microscopy (Revolve Echo). Quantitative transfection efficiency measurements were made using 96 well plate-based fluorescence measurements (Tecan Spark). Culture media was aspirated from cells prior to washing with PBS (Gibco). 35 L lysis buffer (100 mM Tris-HCl, pH 7.5; 0.05% SDS; 25 g/mL Proteinase K) was added to each well. The samples were then incubated at 37 C. for 1 hour before being transferred to 96-well PCR plates and boiled at 98 C. for 15 min. Guide-specific primers were used to PCR amplify the genomic target region of interest from the cell lysates (Q5 DNA Polymerase NEB). Five samples per plate were spot-checked via gel electrophoresis to confirm the presence of the expected amplicon size. The Mag-Bind RxnPure Plus (Omega Bio-tek) PCR clean-up kit was used to purify the PCR products prior to sequencing submission. Once cluted, DNA yields were quantified via the QuantiFluor kit (Promega). DNA concentrations were normalized to 2 ng/100 bp of amplicon length and submitted to the UC Berkeley Sequencing facility for Sanger sequencing along with the appropriate forward PCR primer. PCR and Sanger sequencing primers are listed in Table 2.

Sequencing Analysis

[0157] To quantify base editing efficiency from Sanger sequencing data (FIGS. 1-4), an open-source program called Beat using default parameters (Xu et al. CRISPR J 2019). Beat is a Python-based program that determines editing efficiency after subtracting the background noise and without the need to normalize to control samples. Beat produces results that are concordant with EditR (another commonly used software for base editing) and agree with base editing quantification based on NGS.

[0158] For short read Illumina NGS analysis, target sites were amplified for base editing quantification using a two-step PCR reaction. First, 5 L of lysate (corresponding to 110{circumflex over ()}3 cells) was used as a template for PCR (Invitrogen Platinum SuperFi II PCR Master Mix) with unique primer pairs containing an internal locus-specific region and an outer Illumina-compatible adapter sequence (Table 2). The resulting product was then diluted 1:100 in nuclease-free water and used as a template in a second PCR reaction targeting the outer-adapter sequence, appending unique indices (xGen UDI 10nt Primer Plates 1-16, IDT) to each amplicon for pooled sequencing. Amplicons were pooled 1:1 and sequenced on a NovaseqX with 2151 paired end reads (Seqmatic). All amplicons across experiments included reference samples that were not treated with active base editors to control for any variant reads relative to reference genome that are not due to editing. Base editing efficiencies were calculated using CRISPResso analysis (FIG. 5). Reads were trimmed and filtered using fastp. CRISPResso2 was run in base editing mode with default parameters using the processed reads, amplicon sequences, and spacer sequences as input.

TABLE-US-00001 TABLE1 GuideRNA Sequence SEQIDNO: HEK2-gRNA GAACACAAAGCAUAGACUGC 777 HEK3-gRNA GGCCCAGACUGAGCACGUGA 778 CD3G1 ACAUACUUCUGUAAUACACU 779 T39 GGACAGCUUUUCCUAGACAG 780 Non-targeting- GAGCAGAUCGUUGAUUGUAG 781 gRNAcontrol

TABLE-US-00002 TABLE2 Sequencing SEQ Primer Sequence IDNO: HEK2forward(A) CTGGTGGTACTTGAATCAAGCAC 782 HEK2reverse(A) GAAGGAGACTTGTGCACATTCTATAG 783 HEK3forward ATGTGGGCTGCCTAGAAAGG 784 HEK3reverse CCCAGCCAAACTTGTCAACC 785 HEK2forward(B) ACACTCTTTCCCTACACGACGCTCTT 786 CCGATCTCAAGACCTGGCTGAGCTAA C HEK2reverse(B) GACTGGAGTTCAGACGTGTGCTCTTC 787 CGATCTAAATTGTCCAGCCCCATCTG CD3G1forward ACACTCTTTCCCTACACGACGCTCTT 788 CCGATCTTGATCGGCTTCCTAACTGA AG CD3G1reverse GACTGGAGTTCAGACGTGTGCTCTTC 789 CGATCTAAGCTCACCAGAACAGCAAA T39forward ACACTCTTTCCCTACACGACGCTCTT 790 CCGATCTCTGGCCTGGGTCAATCCTT G T39reverse GACTGGAGTTCAGACGTGTGCTCTTC 791 CGATCTTCCCTAGGTGCTGGCTTCCA

TABLE-US-00003 Sequences SEQID NO: DeaminaseSequence 1 MDDQGWMKLALEEARASRAAGEVPVGAVVVRDGQIVASAGNRTRELCDPTAHAEI VALRQAARALGNYRLPGCTLYVTLEPCAMCAGAMVHARLDRLVYGVPNPKAGAAG SVLDVLHHPRLNHRLEVTGGVLEDECGALLRDFFRAR 2 MDPEDVAFMRKALDEARKAREAGEVPVGAVVVKDGEIVARAHNRTIQKSDPTAHA EILALRKAARALGNYRLTGCTLYATLEPCAMCAGAILHARIERLVYGVPNPKAGATG SVLNVLNHPRLNHRVEVTGGVLAEECGALLRGFFRAR 3 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 4 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDNDPTAHAEI VALREAARRLGSYRLAGCTLYVTLEPCPMCAGAMIHARLDRLVYGVANPKAGAAG TVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 5 MDDKGFMQLALEEARAAQAAGEVPVGAVVVRDGEVLARAGNRTRELCDPTAHAEI VALREAARKRGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRLEVTGGVLEAECGALLRDFFRAR 6 MDDKGWMRLALEEARAAKAAGEVPVGAVVVRDGQVLARAGNQVRELCDPTAHAE IVALREAARKLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAA GSVLDVLGHPRLNHRLEVEGGVLADECGQLLRDFFRAR 7 MDPEDLRFMRQALAEARRAAEAGEVPVGAVVVLDGEVVAQAFNRTRAQSDPTAHA EILALREAARATGNYRLTGCTLYVTLEPCAMCAGAILHARIARLVYGVANPKAGAAG SVLDVLNHPRLNHRVEVTGGVLAEECGALLRDFFRAR 8 MNDEGWMQLALEEARKAKAAGEVPVGAVVVRDGEVIAMAGNRTRERCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRMEVTGGVLEEECGRLLRDFFRAR 9 MDDEGWMKLALEEARAARAAGEVPVGAVVVKDGEVIARAGNRTRELCDPTAHAEII ALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAGS VLDVLGHPRLNHRMEVTGGVLEAECGQLLRDFFRAR 10 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAAKALGNYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 11 MDPTDIAFMRQALAEARKAKDAGEVPVGAVVVHDGEIVARAHNRTILESDPTAHAEI LALRAAARRLGNYRLTGCTLYVTLEPCAMCAGAILHARIERLVYGVANPKAGAAGS VLNVLNHPRLNHRVEVTGGVLADECGALLSGFFRAR 12 MDDEDWMRLALEEARKARAAGEVPVGAVVVRDGQVLARAGNRTRELCDPTAHAEI IALRQAARRRGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVPNPKAGAAGS VLDVLHHPRLNHRLEVTGGVLEAECGALLRDFFRAR 13 MDPDDVEFMRQALDEARRARDAGEVPVGAVVVHDGRVVARAHNRVIAESDPTAHA EIRALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVPNPKAGATG SVLDVLNHPRLNHRVEVTGGVLEEECGRLLSGFFRAR 14 MDDQGWMQLALEEARAARAAGEVPVGAVVVRDGEVLARAGNRTRELCDPTAHAEI RALREAARALGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVRNPKAGAAG SVLDVLGHPRLNHRLEVTGGVLEAECGALLRDFFRAR 15 MDPEDIEFMKKALAEARAAKEAGEVPVGAVVVSDGEVVARAHNQTIERSDPTAHAE ILALRAAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIERLVYGVANPKAGAAGS VLDVLNHPRLNHRVEVTGGVLAEECGALLSDFFRAR 16 MDDEGWMRLALEEARAARAAGEVPVGAVVVRDGQVLAQAGNRTRELCDPTAHAEI VALREAARALGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAA GSVLDVLGHPRLNHRAEVEGGVLADECGALLRDFFRAR 17 MDPEDREFMRKALEEARKAREAGEVPVGAVVVLDGRIVARAHNQTRAESDPTAHAE ILALREAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIERLVYGVPNPKAGATGS VLNVLNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 18 MDDEGWMQLALEEARASKAAGEVPVGAVVVRDGRVLARAGNRTRERCDPTAHAEI VALREAARRLGNYRLTGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLHHPRLNHRLEVEGGVLEAECGQLLRDFFRAR 19 MDDRGWMKLALEEARAAKAAGEVPVGAVVVRDGEVIARAGNRTRLKCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRLEVTGGVLAAECAALLRDFFRAR 20 MDDEGWMRLALEEARKAKAAGEVPVGAVVVRNGEVIARAGNRTRELCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRLEVEGGVLEAECGALLRDFFRAR 21 MDPMDIAFMQQALDEARKAKEAGEVPVGAVVVHDGQIVARAHNRTIALSDPTAHA EILALREAARALGNYRLQGCTLYATLEPCAMCAGAILHARIARLVYGVPNPKAGACG SVLNVLNHPRLNHRVEVTGGVLAEECGALLRGFFRAR 22 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 23 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAGHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 24 MDAALEEARRAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARAAGNYRLPGATLYVTLEPCAMCAGAMIHARLDRLVYGAADPRAGAAGSVFDVL RHPALNHQMAVEGGVRAAECGALLRDFFRARR 25 MTDADFMALALEEARAAAALGEVPVGAVVVRDGAVIARAGNRTIRDCDPTAHAEIV ALREAARALGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPKTGAAGS VLDVLNHPKLNHQMQVEAGVLAEECGAMLRDFFQQRR 26 MRDALAEARKAADAGEVPVGAVVVRGGEILARAHNRTVADHDPTAHAEILALREA ARVLGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRLVYGAADPKAGAAGSVLDVL NHPRLNHRMEVEGGVLAEESGELLRGFFRARR 27 MDDAGFMREALAEARAAAAAGEVPVGAVVVKDGEIIARAGNRTLRDNDPTAHAEIV ALRAAARALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGADDPKGGAVAHG PRFFAQPTCHHRPEVTGGVGAEEAGALLRDFFRARR 28 MREALAEARAAAEAGEVPVGAVVVRDGEIIARARNRMVADCDPTAHAEIVALREAA RVLGNHRLTGCTLYATLEPCAMCAGAIAHARIARLVYAADDPKGGAVWHGPRFFEQ PTCHHRPEVTSGVLADEAAALLRDFFRARR 29 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 30 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRLF AQPTCHHRPEVVGGVGAAEAGALLRDFFAARR 31 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVEDVL RHPALNHRMEVEGGVLAEECGALLREFFRARR 32 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHGPRFFA QPTCHHRPEVTGGVLAAEAGELLRGFFRARR 33 MRDALAEARAAAAAGEVPVGAVVVRDGAIVARARNRMVADCDPTAHAEIVALRAA ARALGNHRVDGCTLYVTLEPCAMCAGAMIHARLARLVYGAADPRAGAAGSVLDVL GHPALNHRMEVTAGVLAEECGALLRDFFAARR 34 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVFDILR HPALNHRMEVEGGVLAEECGALLRDFFRARR 35 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF EQPTTHHRPEVVGGVLAEEAAALLRGFFAARR 36 MRAALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRAFFRARR 37 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAAEAGALLRDFFRARR 38 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAMVQARLARLVYGAADPKAGAVDSVLDV LDHPRLNHRMEVTGGVLAEECGALLREFFAARR 39 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFEQ PTCHHRPDVTGGVGAAEAAALLRDFFRARR 40 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARARNAPVAAHDPTAHAEI LALRAAAAALGNYRLDGCTLYVTLEPCAMCSGAMLHARLARVVYGAADPKTGAAG SVLDLFAQPRLNHHTAVEGGVLAAECGALLRDFFRARRG 41 MDDEFFMREALRLAEEAAAAGEVPVGAVVVRDGEIVGRGRNRVLEDRDPTAHAEIV ALREAARRLGNYRLEGCELYVTLEPCAMCAGAMVHARLARLVYGAADPKAGAAGS VLDVLGHPRLNHRMEVTGGVLAEECGALLREFFRARR 42 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPDVTGGVGAAEAAALLRDFFRARR 43 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRE AARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRL FAQPTCHHRPEVVGGVGAAEAAALLRGFFAARR 44 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLGGCDLYVTLEPCAMCAGAISFARIRRLYFGADDPKGGAVE HGPRFFAQPTCHHAPEVYGGLAESEAAALLRDFFRARR 45 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLEGCTLYVTLEPCAMCAGAMLHARLARVVYGAADPKTGA AGSVLDLFANPRLNHHTRVEGGVLAEECGALLQDFFRARRG 46 MSDEDYMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARKLGNYRLAGCTLYVTVEPCAMCAGALVWARVDRLVYGADDPKAGAV RSALAVVDHPRLNHRMEVVSGVLAGECAALLQEFFAARR 47 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 48 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVTGGVGEAEAAALLRDFFAARR 49 MTDEYFMRQALREARKAYDEDEVPVGAVVVRDGKVIARGRNQVERLKDPTAHAEM IALTSAANYLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGTL YDIPGDRRLNHRIEVVGGVLEEESAALLREFFEKRR 50 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 51 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAGEAAALLRDFFAARR 52 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLEGCDLYVTLEPCAMCAGAISFARIRRLYFGAADPKGGAVE HGPRFFAQPTCHHAPEVYGGLAESEAAALLRGFFAARR 53 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF EQPTTHHRPEVVGGVLAAEAGALLRAFFAARR 54 MTEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTVTDADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAIVHARVDRLVYGAADPKAGAAGSVLDVIG HPRLNHRPEVEGGVLGEECGALLRDFFRARR 55 MRSALDLAAAAAAAGEVPVGAVVVRDGAIVGRGENRVLRDSDPTAHAEIVAMREA ARALGNYRLTGCTLYVTLEPCAMCAGAMVHARLDRLVYGAADPKAGAAGSVLDVL GHPRLNHQMEVEGGVLAAESAALLRDFFRARR 56 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 57 MDDAGFMRLALAEAEAAAAAGEVPVGAVVVRDGEVIARAGNRTVRDCDPTAHAEI VALRAAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVA HGPRFFAQPTCHHRPEVAGGVLAEEAGALLRGFFRARR 58 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAEI VALRAAARALGNYRLDGCDLYVTLEPCAMCAGAMLHARLRRVVFGAADPKTGAA GSVLDLFAERRLNHRTAVAGGVLADECGALLRDFFRARR 59 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLDGCDLYVTLEPCAMCAGAISHARIRRLYYGADDPKGGAV DNGVRFFASPTCHHAPEVYGGLAEGEAAALLRDFFRER 60 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVVGGVGAEEAGALLRGFFAARR 61 MTEALREARRAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVGEAEAAALLRDFFRARR 62 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRA AARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRL FAQPTCHHRPEVVGGVGEAEAAALLRDFFAARR 63 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 64 MTDEYFMRQALREARRAYEEDEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAANHLGSKRLEGCTVYVTLEPCPMCAGALVLARVPRLVFGAFDPKAGACGTL YDIVRDPRLNHRVEVVGGVLEEECGELLKRFFRERR 65 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVVGGVGAAEAGALLRDFFAARR 66 MTEALAEARKAAAEGEVPVGAVVVRDGVVLARAHNRTVADHDPTAHAELLAIREA ARVLGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRLVYGAADPKAGAAGSVLDVL GHPRLNHRPEVEGGVLAAESAALLRDFFRARR 67 MDDAGFMRLALAEAERAAALGEVPVGAVLVRDGEVLAAAGNRTVADCDPTAHAE MLALREGARRLGNYRLTGCTLYVTLEPCAMCAGAMVHARLDRLVYAAADPKAGA AGSVLDVLNHPALNHRMQVEGGVLAEESAALLRGFFRARR 68 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRVGGATLYVTLEPCAMCAGAISQARVARLVYGADDPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAEESAALLRGFFAARR 69 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAAEAGALLRDFFRARR 70 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPDVTGGVLAEEAGALLRDFFRARR 71 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAADYLGSKRLEGCTLYVTLEPCAMCAGAIVLARIPRLVFGAFDPKAGACGTL YDIVRDRRLNHRAEVVSGVLEEECGALLKEFFARLR 72 MDDEFFMREALRLAEEAAAAGEVPVGAVVVRDGEIVGRGRNRVLEDRDPTAHAEIV AMREAARRLGNYRLEGCTLYVTLEPCAMCAGAMVHARVARLVYGAADPKAGAAG SVLDVLGHPRLNHRMEVTGGVLAEECGALLREFFRRRR 73 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRAA AAALGQERLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 74 MREALAEARAAAAAGEVPVGAVVVRDGAIVARARNRMVADCDPTAHAEIVALREA ARALGNHRLDGCTLYVTLEPCAMCAGAMVHARVARLVYGAADPRAGAAGSVLDV LGHPALNHRMEVAGGVLAEECGALLREFFAARR 75 MRAALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAEEAGALLRDFFRARR 76 MRAALDEARAAAAAGEVPVGAVVVRDGAILARAGNRTVRDCDPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVRHGPRFFE QPTCHHRPEVVGGVGAEEAAALLRGFFAARR 77 MDDEAWMRRAIALAHQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGHHDATAHAEI ETLRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYAEVESGLLEQECREQLQAFFKRRRKEIKALRQAQRDAE 78 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLEGCDLYVTLEPCAMCAGAIAHARIARLYYGAADPKGGAV EHGARVFDQPQCLHRPEVYGGIGEAEAAALLRGFFAARR 79 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVAGGLGEAEAGALLRDFFAARR 80 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVVGGVGEAEAAALLRAFFAARR 81 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPEVTGGVGEAEAAALLRAFFAARR 82 MTDEYFMRQALREARRAYEEDEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAANHLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGT LYDIPGDRRLNHRLEVVGGVLEEESAALLREFFRKRR 83 MTDEDYMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARVLGNYRLAGCTLYVTVEPCAMCAGAIVHARVARLVYGADDPKGGAVR SCLEVLDHPRLNHRVEVTAGVLAGECAALLQDFFAARR 84 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVLALRA AARALGSERLTGCTLYVTLEPCAMCAGAISHARVARLVYGAADPKGGAVEHGARVF EQPTCHHRPEVVGGVGAAEAGALLRDFFAARR 85 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFEQ PTCHHRPEVTGGVLAEEAGALLRAFFRARR 86 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGAVLARAGNRTLRDRDPTAHAE MVALRAAARALGSERLTGCDLYVTLEPCAMCAGAISFARIRRLYFGAADPKGGAVE NGVRFFASPTCHHAPEVYGGLAESEAAALLRDFFRARR 87 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAGHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGARDPKAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRERR 88 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAEEAGALLREFFRARR 89 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFAQ PTCHHRPEVTGGVLAEEAGALLRAFFRARR 90 MSDEQYMRRALELARQAEQAGEVPVGAVLVKDGEIIAEGWNQSISAHDATAHAEIM ALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKALRQAQREAEE 91 MSEEQYMRRALELARQAEQEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATGHAEIM ALRAAGEKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQKEAE 92 MDDAGFMRLALAEARRAAEAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALREAARALGNHRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAV AHGARVFDQPTCHHRPEVYGGIGAAEAAALLRDFFRARR 93 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAAEAGALLRDFFRARR 94 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPDVTGGVLAEEAGALLRDFFRARR 95 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVVGGVGEAEAGALLRDFFAARR 96 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAAHLGSKRLEGCTVYVTLEPCAMCAGALVLARVDRLVFGAFDPKAGACGT VYDIPRDRRLNHRVEVVGGVLEEESAALLRAFFEERR 97 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVVGGVGAEEAAALLRGFFAARR 98 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAADHLGSKRLEGCTLYVTLEPCAMCAGAIVLARIPRLVFGAFDPKAGACGTL YDIVRDRRLNHRVEVVSGVLEEESAALLREFFAERR 99 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPDVVGGVGAAEAGALLRDFFRARR 100 MTDEYFMRQALREARRAYDEDEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTSAANHLGSKRLEGCTVYVTLEPCPMCAGALVLARVPRLVFGAFDPKAGACGTL YDIPRDRRLNHRVEVVGGVLEEESAALLREFFARRR 101 MTEALAEARKAAAAGEVPVGAVLVRDGEILARGGNRTIRDCDPTAHAEIVALREAA RKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGADDPKAGAAGSVLDVLN HPRLNHQMEVTRGVLADECGALLRDFFQARR 102 MTDEYFMRQALREARRAFDEDEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IAITSAANYLGSKRLEGCTVYVTLEPCPMCAGALVLARVPRLVFGAFDPKAGACGTL YDIPRDRRLNHRLEVVGGVLEEESAALLREFFARRR 103 MTDEDYMRLALEEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAEI VALRAAARALGNYRLPGCTLYVTVEPCAMCAGAMIHARLDRLVYGADDPKAGAVR STLRVLDHPALNHRMAVTAGVLADECAALLQDFFRARR 104 MREALAEARAAAAAGEVPIGAVVVRDGAVLARAGNRTVRDCDPTAHAEIVALREA ARALGNHRLTGCTLYVTVEPCAMCAGAISWARVARLVYGAADPKGGAVRHGPRLF EQPTCHHAPEVVDGVCAEEAAALLRDFFRARR 105 MDDEALMGLALDEARAAAAAGEAPIGAVVARGGEVLAAAGNRTLRDCDPTAHAEI LALREAARKLGNYRLTGCTLYATLEPCAMCAGAISHARIARLVYGADDPKGGAVRH GPRFFEQPTCHHRPEVAGGVGAAEAGALLRDFFRARR 106 MDDEALMGLALDEARAAAAAGEAPIGAVVARGGEVLAAAGNRTLRDCDPTAHAEV LALREAARRLGNYRLTGCTLYVTLEPCAMCAGAISHARVARLVYGAADPKGGAVA HGPRFFEQPTCHHRPEVTGGVGAAEAGALLRDFFRARR 107 MSDEQYMRRALELARQAEAEGEVPVGAVLVRDGEVIAEGWNRSIGSHDATGHAEIM ALRAAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQREAEEK 108 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVLDVIG HPALNHRMAVEGGVLAEECGALLRDFFRARR 109 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAAHLGSKRLEGCTLYVTLEPCAMCAGAIVLARVPRLVFGAFDPKAGACGT LYDIVRDRRLNHRVEVVSGVLEEESAALLREFFARLR 110 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF EQPTTHHRPEVVGGVLAEEAGALLRGFFAARR 111 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAAEAGALLRDFFRARR 112 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAAEAGALLREFFAARR 113 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFEQ PTCHHRPEVTGGVLAEEAGALLRDFFRARR 114 MDDAGFMRLALAEAEAAAAAGEVPVGAVVVRDGEVIARAGNRTVRDCDPTAHAEI VALREAARKLGNYRLPGCTLYVTLEPCAMCAGAMIHARLDRVVYGAADPKTGAAG SVLDLFADRRLNHHTAVVGGVLAEEAGALLRAFFAARR 115 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRAFFRARR 116 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 117 MRAALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAAEAGALLRDFFRARR 118 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARLARLVYGAADPKGGAVEHGPRFFA QPTCHHRPEVTGGVGAAEAGALLRAFFAARR 119 MSDEQFMRRAIELAKKGEELGEVPVGAVLVKDGEIIAEGWNQSISTHDATAHAEIMA LRAAGEKLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVL NLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKAKKEAEQK 120 MREALAEARAAAAAGEVPIGAVVVRDGAVLARAGNRTVRDCDPTAHAEIVALREA ARALGNYRLDGCTLYVTLEPCAMCAGAMLHARLARVVYGAADPKTGAAGSVLDLF AERRLNHQTEVAGGVLAEECGALLRDFFRARRG 121 MTEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTVTDTDPTAHAEIVALREAA RALGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRVVYGAADPKAGAAGSVLDVLG HPRLNHRPEVAGGVLAAESAALLRDFFRARR 122 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAAHLGSKRLEGCTLYVTLEPCAMCAGAIVLARIPRLVFGAFDPKAGACGTL YDIVRDRRLNHRAEVVSGVLEEECGALLKEFFARLR 123 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVVGGVGEAEAAALLRGFFAARR 124 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRAA ARALGSERLTGCTLYVTLEPCAMCAGAISHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 125 MTDEYFMRQALREARRAYEEDEVPVGAVVVREGRVIARGRNQVERLKDPTAHAEMI ALTSAANYLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGTL YDIPGDRRLNHRIEVVGGVLEEESAALLREFFRRRR 126 MSEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTVADADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRLVYGAADPKAGAAGSVLDVL GHPRLNHRPEVEGGVLAAESAALLRDFFRARR 127 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATGHAEIM ALRAAGEKLGNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAARKAKREAEEK 128 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRAFFRARR 129 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPKAGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRARR 130 MRAALDEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFFA QPTCHHRPEVTGGVLAAEAGALLRDFFRARR 131 MTEALAEARKAAAAGEVPVGAVVVRDGEILARAHNRTVADHDPTAHAEILALREAA RRLGNHRLTGCELYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVEHGPRFFAQP TCHHRPEVVGGVGASEAAALLRDFFRARR 132 MRAALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAEEAGALLRAFFRARR 133 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAE VVALREAARKLGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAV AHGPRFFAQPTCHHRPEVAGGLLAGEAAALLRDFFAARR 134 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLREFFRARR 135 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVEDVIR HPALNHRMEVEGGVLAEECGALLRDFFRARR 136 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHGPRFFA QPTCHHRPEVVGGVGAEEAGALLRDFFRARR 137 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAAHLGSKRLEGCTLYVTLEPCAMCAGAIVLARIPRLVFGAFDPKAGACGTL YDIVRDRRLNHRVEVVSGVLEEESAALLREFFARLRA 138 MSDEQYMRRALELARQAEEEGEVPVGAVLVKDGEIVAEGWNRSIGSHDATGHAEIM ALRAAGEKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAQRDAEKAAAE 139 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAAEAGALLRAFFAARR 140 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPDVTGGVGAAEAAALLRDFFRARR 141 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAEIVALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRLF AQPTCHHRPEVVGGVGAEEAAALLRGFFAARR 142 MTDEYFMRQALREARRAYDEDEVPVGAVVVRDGKVIARGRNQVERLKDPTAHAEM IALTSAANHLGSKRLEGCTVYVTLEPCAMCAGALVLARVDRLVFGAFDPKAGACGT LYDIPRDRRLNHRVEVVGGVLEEESAALLREFFRRRR 143 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGKVIARGRNQVERLKDPTAHAEM IALTAAANHLGAKRLEGCTVYVTLEPCAMCAGALVLARVDRLVFGAFDPKAGACGT LYDIPRDARLNHRVEVVSGVLEEESAALLREFFARLR 144 MSEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAAA RALGNYRLPGTTLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVFDILRH PALNHRMEVEGGVLADECGALLRDFFRARR 145 MRAALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPEVTGGLGEAEAAALLRAFFAARR 146 MRAALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAAEAGALLRDFFRARR 147 MTEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTVADADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRVVYGAADPKAGAAGSVLDVL GHPRLNHRPEVAGGVLAEECGALLRDFFRARR 148 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF EQPTCHHRPEVVGGVLAEEAGALLRGFFAARR 149 MTDEYFMRQALREARRAYEEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAAAHLGNKRLEGCTLYVTLEPCAMCAGAIVLARIPRLVFGAFDPKAGACGTL YDIVRDRRLNHRAEVVSGVLEEECGALLKEFFARLR 150 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVVGGVGEAEAAALLRDFFAARR 151 MDDEFYMRRALELAALAEEHNEVPVGAVLVLNGEIIGEGWNRSIGHHDATAHAEIM ALRQAGKKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEIKALKKAKREAE 152 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFFA QPTCHHRPEVTGGVLAAEAGALLRDFFRARR 153 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAANHLGAKRLEGCTVYVTLEPCAMCAGALVLARVDRLVFGAFDPKAGACGT LYDIPRDPRLNHRVEVVSGVLAEESAALLREFFAARR 154 MTDEYFMRQALREARRAYEEDEVPVGAVVVREGRVIARGRNQVERLKDPTAHAEMI ALTAAANHLGSKRLEGCTVYVTLEPCPMCAGALVLARVRRLVFGAFDPKAGACGTL YDIPRDRRLNHRVEVVGGVLEEESAALLREFFRRRR 155 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEVVAEGWNRSIGSHDATGHAEI MALRAAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVYGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAARQAKRDAE 156 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRA AARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRL FAQPTCHHRPEVVGGVGAAEAAALLRDFFAARR 157 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNYRLDGCTLYVTLEPCAMCAGAMLHARLARVVYGAADPKTGA AGSVLDLFAQPRLNHHTQVEGGVLAAECGALLQDFFRARRG 158 MSDEQFMRRAIELARKGEELGEVPVGAVLVKDGEIIAEGWNQSISTHDATAHAEIMA LRAAGEKLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVL NLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKAKREAEEK 159 MREALAEARAAAAAGEVPVGAVVVRDGVVLARAGNRTVRDADPTAHAEVVALRA AARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRL FEQPTCHHRPEVVGGVLAEEAGALLRDFFAARR 160 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVEHGPRFFA QPTCHHRPEVVGGVGAAEAGALLRDFFRARR 161 MSDEDYMRLALEEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAEI VALREAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVA HGPRFFAQPTCHHRPEVTGGVLAEEAGALLRGFFAARR 162 MTDEYFMRQALREARRAYDEDEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTSAANYLGSKRLEGCTVYVTLEPCAMCAGALVLARVDRLVFGAFDPKAGACGT LYDIPGDRRLNHRVAVTGGVLEEESAALLREFFRERR 163 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEIVAEGWNRSIGSHDATAHAEIE TLRKAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAEKEAAEK 164 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAEEAGALLRDFFRARR 165 MRDALAEARAAAARGEVPVGAVVVRDGAVLARAGNASIAARDPTAHAEILALRAA ARALGNHRLAGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVGAAEAGALLRDFFAARR 166 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRAA ARALGSERLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHGPRFFA QPTCHHRPDVTGGVGEAEAGALLRAFFAARR 167 MDDAGFMRLALAEARKAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALREAARALGNHRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAV AHGARVFDQPTCHHRPEVYGGIGAAEAAALLRGFFAARR 168 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAAHLGSKRLEGCTLYVTLEPCAMCAGAIVLARLPRLVFGAFDPKAGACGTL YDIVRDRRLNHRVEVVSGVLEEECGALLKEFFARLR 169 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATGHAEIM ALRAAGEKLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQKAAE 170 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFEQ PTCHHRPEVTGGVGAAEAGALLRDFFAARR 171 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVVLREAA RALGNYRLEGCTLYVTLEPCAMCAGAMIHARLDRLVYGADDPKAGAAGSVLDVLN HPRLNHQMEVTAGVLAEECGALLREFFRARR 172 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRAA ARALGSERLTGCTLYVTLEPCAMCAGAISHARIARLVYGADDPKGGGVAHGARVFD HPQCHHRPEVVGGVGAAEAAALLRDFFAARR 173 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRAA AAALGSERLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRLFA QPTCHHRPEVVGGVGEAEAAALLRDFFAARR 174 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRAFFRARR 175 MRDALAEARAAAARGEVPVGAVVVRDGAILARAGNATVAASDPTAHAEILALRAA ARALGSQRLPGAVLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 176 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRLFAQ PTCHHRPEVTGGVGAAEAAALLRDFFRARR 177 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAAAHLGNKRLEGCTLYVTLEPCAMCAGALVLARVPRLVFGAFDPKAGACGT LYDIVRDRRLNHRVEVVSGVLEEESAALLKEFFARLR 178 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAE VVALREAARKLGNHRVTGATLYVTLEPCAMCAGAISLARVARLVYAADDPKGGGV AHGARVFDQPTCHHRPEVVSGVLAEESAALLRGFFAARR 179 MTDEYFMRQALREARRAYDEDEVPVGAVVVREGKVIARGRNQVERLKDPTAHAEM IALTSAANHLGSKRLEGCTVYVTLEPCAMCAGALVLARVERLVFGAFDPKAGACGT LYNIPADRRLNHRVEVVGGVLEEESAALLREFFRKRR 180 MDDEAWMRRAIALAHQAEAEGEVPVGAVLVKDGEVVAEGWNRSIGSHDATAHAEI ETLRKAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQREAE 181 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLEGCTLYVTLEPCAMCAGAALQARLARLVYGAAEPKTGAA GSVLDVFANPALNHHTAVTGGVLAAEAAALLRDFFAARR 182 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARAAGNYRLPGATLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVFDVV RHPALNHRMAVEGGVLAEECGALLRDFFRARR 183 MTEKDKFFMQRAIELAKLAEENGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAHAEI MALRQAGKVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKAKKEAE 184 MTDEYFMRQALREARRAYDEDEVPVGAVVVRDGKVIARGRNQVERLKDPTAHAEM IALTSAANYLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGTL YDIPGDRRLNHRLEVVGGVLEEESAALLREFFRRRR 185 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAAEAGALLRDFFRARR 186 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAAAHLGNKRLEGCTLYVTLEPCAMCAGAIVLARIPRLVFGAFDPKAGACGTL YDIVRDRRLNHRAEVVSGVLEEECGALLKEFFARLR 187 MSDEQYMRRALELARQAEQAGEVPVGAVLVKDGEIIAEGWNQSISSHDATAHAEIM ALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALKQAKREAEQK 188 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNYRLDGCTLYVTLEPCAMCAGAMLHARLARVVYGAADPKTGA AGSVLDLFAEPRLNHHTRVEGGVLAAECGALLRDFFRARRG 189 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDRDPTAHAE MVAIRAAAAALGQERLTDCDLYVTLEPCAMCAGAISFARIRRLYFGAADPKGGAVE HGPRFFAQPTCHHAPEVYGGIGEGEAAALLRDFFRARR 190 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRA AARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRL FEQPTTHHRPEVVGGVLAEEAAALLRGFFAARR 191 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGARVF DQPQTHHRPEVTGGVLAEEAGALLRAFFAARR 192 MDDAGFMRLALAEARRAAEAGEVPVGAVVVRGGEVLAAAGNRTLRDCDPTAHAEI VALREAARRVGNYRLADCDLYVTLEPCAMCAGAIVHARVRRLVYGADDPKAGAVR SALRVLDAPALNHRVEVTAGVLAEECGALLRDFFRARR 193 MTEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTVTDADPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAMVHARLDRLVYGAADPKAGAAGSVLDVL GHPRLNHQMEVTAGVLADESAALLRDFFRARR 194 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEMLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVVGGVGAAEAGALLRDFFAARR 195 MTEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTVTDTDPTAHAEIVALREAA RALGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRVVYGAADPKAGAAGSVLDVLG HPRLNHRPEVEGGVLGEECGALLRDFFRARR 196 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRE AARALGNHRLGGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVRHGARV FDQPTCHHRPEVVGGVLAEESAALLRGFFAARR 197 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVVGGVGAAEAGALLRAFFAARR 198 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAV AHGARVFAHPQCHHRPEVYGGIGAAEAAALLRDFFAARR 199 MTDEYFMRQALREARRAYDEDEVPVGAVVVRDGKVIARGRNQVERLKDPTAHAEM IALTSAANHLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGTL YDIPGDRRLNHRVEVVGGVLEEESAALLREFFRRRR 200 MDDEFYMRRALELAALAEEHNEVPVGAVLVLNGEIIGEGWNRSIGHHDATAHAEIM ALRQAGKKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEKKALKQAQKEAE 201 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVEHGPRFFA QPTCHHRPEVVGGVGAAEAAALLRDFFRARR 202 MRAALDEARAAAAAGEVPVGAVVVRDGAILARAGNRTVRDCDPTAHAEIVALREA ARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHGPRFFA QPTCHHRPEVVGGVGAGEAAALLRDFFAARR 203 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRAFFRARR 204 MRDALAEARAAAARGEVPVGAVVVRDGAVLARAGNATVAASDPTAHAEILALRAA ARAAGNHRLPGAVLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 205 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNRTVRDADPTAHAEIVALREA ARALGNHRLGGCTLYVTLEPCAMCAGAISQARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVAGGLGEAEAAALLRDFFAARR 206 MTEALAEARKAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVEDVL RHPALNHRMEVEGGVLAEECGALLRDFFRARR 207 MTEKDKFFMQRAIELAKKGEENGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAHAEI MTLREAGKVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEKKALKQAKREAEQK 208 MTDEDYMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARALGNYRLTGCTLYVTIEPCAMCAGAMIHARVDRLVYGAADPKAGAVR STLRVLDHPALNHRVEVTAGVLADECAALLQDFFRSRR 209 MRDALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRA AARALGSERLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPDVTGGVGEAEAGALLRDFFAARR 210 MREALAEARAAAAAGEVPIGAVVVRDGAVLARAGNRTVRDCDPTAHAEVVALREA ARALGNHRLTGCTLYVTVEPCAMCAGAISHARVARLVYGADDPKGGAVRHGPRFFE QPTCHHRPEVVGGVGAEEAAALLRDFFRARR 211 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFF EQPTCHHRPEVTGGVLAEEAGALLRAFFAARR 212 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAAHLGSKRLEGCTLYVTLEPCAMCAGAIVLARVPRLVFGAFDPKAGACGT LYDIPRDRRLNHRAEVVGGVLEEESAALLREFFAARR 213 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVVGGVGAAEAGALLRGFFAARR 214 MDDEAWMRRAIALAHKAEQEGEVPVGAVLVKDGEVIAEGWNRSIGHHDATAHAEI ETLRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQKAAE 215 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALREA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVVGGVGEAEAAALLRGFFAARR 216 MRDALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFEQP TCHHRPEVTGGVLAEEAGALLRAFFRARR 217 MSDEQYMRRAIELARQAEQEGEVPVGAVLVKDGEIIAEGWNRSIGSHDATAHAEIET LRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVL NLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAARKAKREAEQ 218 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGEVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLDGCDLYVTLEPCAMCAGAISHARIRRLYYGADDPKGGAV DNGVRFFASPTCHHAPEVYSGLAESEAAALLRDFFRERR 219 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRA AARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRL FEQPTCHHRPEVVGGVGEAEAAALLRGFFAARR 220 MTDEYFMRQALREARRAYDEDEVPVGAVVVREGKVIARGRNQVERLKDPTAHAEM IALTSAANYLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGTL YDIPGDRRLNHRVEVVGGVLEEESAALLREFFRRRR 221 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNASIRARDPTAHAEILALRAAA RALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFEQ PTCHHRPEVTGGLGEAEAAALLRDFFRARR 222 MTDEYFMRQALREARRAYEEDEVPVGAVVVREGRVIARGRNQVERLKDPTAHAEMI ALTAAANHLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGTL YDIPGDRRLNHRVEVVGGVLEEEAAALLREFFRRRR 223 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNYRLDGCTLYVTLEPCAMCSGAMLHARLARVVYGAADPKTGA AGSVLDLFAEPRLNHHTRVEGGVLAGECGALLADFFRGRRG 224 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLDGCDLYVTLEPCAMCAGAIAHARIRRLYYGAADPKGGAV EHGARVFDQPTCHHRPEVYGGIGEAEAAALLRDFFRDR 225 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEIIAEGWNRSIGSHDATGHAEIM ALRAAGEKLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQKAAE 226 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPDVTGGVGAAEAAALLRDFFRARR 227 MREALAEARAAAAAGEVPVGAVVVRDGAILARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAAVLARVARLVFGADDPKGGAVRTGVRLF DAPTCHHRPEVTGGVLAEEAGALLREFFAARR 228 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAELVAIRAA ARALGSERLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFAQ PTCHHRPEVTGGVGEAEAAALLRGFFAARR 229 MTDEDYMRLALEEARAAAAAGEVPVGAVVVRDGEVIARARNAPVSACDPTAHAEIL ALREAARRLGNYRLDGCTLYVTLEPCAMCSGAMLHARLARVVYGAADPKTGAAGS VLDLFAEPRLNHHTAVEGGVLAAECGALLRDFFRARRG 230 MSDEQYMRRALELARQAEAEGEVPVGAVLVKDGEVVAEGWNRSIGSHDATGHAEI MALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKAARKAAKAAAE 231 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRAHDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLREFFRARR 232 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEVVALRA AARALGNHRLDGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRL FEQPTCHHRPEVVGGVGEAEAAALLRAFFAARR 233 MTEALAEARKAAALGEVPVGAVVVRDGAVIARGHNRTIADSDPTAHAEIVALREAA RVLGNYRLTGCTLYVTVEPCAMCAGAMVHARLDRLVYGAADPKAGAAGSVLDVL GHPRLNHQMEVTGGVLAEECAALLRDFFRARR 234 MDDEFYMRRALELAALAEEHNEVPVGAVLVLNGEIIGEGWNRSIGHHDATAHAEIM ALRQAGKVLQNYRLLDTTLYVTLEPCPMCAGALVHSRVKRVVYGTPDLKTGAAGS VMNLLSYEGVNHHVEVTSGVLAEECREQLQAFFRRRRAEKKALKKAQREAE 235 MDDEAWMRRAIALAHQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGHHDATAHAEI ETLRQAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEIKAQRDAQRAAQE 236 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPDVTGGVLAAEAGALLRDFFRARR 237 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGAVLARAGNRTLRDRDPTAHAE VVALRAAARALGSERLTGCDLYVTLEPCAMCAGAISFARIRRLYFGAADPKGGAVEN GVRFFASPTCHHAPEVYGGLAESEAAALLRDFFRARR 238 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAV AHGARVFDQPTCHHRPEVYGGIGAAEAAALLRDFFRARR 239 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVEHGPRFF AQPTCHHRPEVTGGVLAAEAGALLRDFFRARR 240 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLDGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPDVTGGVLAAEAGALLRDFFRARR 241 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRGFFRARR 242 DDDDRRWMREALAEARAAADAGEVPVGAVVVRDGVLLARAGNASIRDRDPTAHA EMLALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKAGAV EHGPRLFAQPTIHHRPEVTAGVLAEECGALLRDFFRARR 243 DPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAEIL ALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSV LDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRARR 244 DDDHAWMGAALAEARAAAEAGEVPVGAVLVADGRVLARAGNRTIRDRDPTAHAE MLALRAAARALGNHRLTGTTLYVTLEPCAMCAGAISLARVARLVYAASDPKGGAVE HGPRFFAQPTCHHRPEVVGGVGEGEAGALLRDFFRARR 245 MTAEDDRFMRLALAEARAAAEAGEVPVGAVVVAGGRVVARAHNRPIALHDPTAHA EVLALRAAARELGNYRLTGCTLYATLEPCAMCAGAVLHARIARLVYGAADPKAGAC GSVLAVMNHPRLNHRVEVTGGVLAEECGALLREFFRARR 246 MDSDLAFMREALAEARAAAEAGEVPVGAVVVHEGKIVARAANRMRTDRDPTAHAE LLALRAAARALETTRLTGCTLYVTLEPCAMCAGAISHARVARLVYGASDPKGGAVE HGPRFFAQPTCHHRPEVVGGVGEAEAGALLRGFFRARR 247 DPDDARWMREALAEARAAAEAGEVPVGAVVVRDGRLLARAGNRTIRDRDPTAHAE MLALRAAARALGNHRLEGCTLYVTLEPCAMCAGAMVQARVARLVYGAADPKAGA AGSVLDVLGDPRLNHRVEVTGGVLAEECGALLREFFRARR 248 MDSDLEFMREALAEARAAAEAGEVPVGAVVVRDGVILARAGNRPIRDHDPTAHAEI LALREAARAVGNYRLTGCTLYVTLEPCAMCAGAILHARVERLVYGAADPKAGAAGS VLDVFGNARLNHHTRVEGGVLAEECGALLSGFFRARRG 249 DPDAEFMRLALAEAEAAARAGEVPVGAVVVADGRVIARAGNRTIRDRDPTAHAEML ALRAAARALGSHRLTGCDLYVTLEPCAMCAGAISHARIRRLYYGAADAKGGAVEHG PRFFAQPTCHHRPEVYGGIGETAAAALLRDFFRARR 250 DPDAAFMRAALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIELNDPTAHAEIL ALRQAAAALGNYRLTGCTLYATLEPCAMCAGAILHARIERLVYGAADPKAGAVGSV LDVFANPRLNHRTQVTAGVLADECGALLREFFRARR 251 DESSDEEFMRAALEEARAAAAEGEVPVGAVVVAGGRIVARAHNRPIALNDPTAHAEI LALRQAAAALGNYRLTGCTLYATLEPCAMCAGAILHARIARVVYGAADPKAGACGS VLAVMNHPQLNHRAEVTGGVLAEECGALLSEFFRARR 252 DDDHRFMRAALAEARAAAEAGEVPVGAVVVHGGEIIARAHNRPIALHDPTAHAEILA LRAAARRLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSVL AVMNHPRLNHRVEVTAGVLADECGALLSEFFRARR 253 MNDEDYMRAALEQARQAAAAGEVPVGAVVVCGGEIVARAHNRPISASDPTAHAEIL ALREAARKLGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGAADPKAGAVGSV LDVINHPRLNHRVEVTSGVLADECGALLKEFFRARR 254 MNDEDYMRAALEQARQAAAAGEVPVGAVVVCDGKIVARAHNRPISANDPTAHAEI LALREAARQLGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGAADPKAGACGS VLNVINHPQLNHQTEVTGGVLADECGALLKDFFRARR 255 MRAALEEARRAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PRLNHRVEVTGGVLAEECGALLTGFFRARR 256 MSEEDRFMRAALAEARAAAEAGEVPVGAVVVCGGRIVARAHNRPIALNDPTAHAEI LALREAARELGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVESL YRLLDDTRLNHRVEAVGGVLAGECGALLSGFFRARR 257 MDEEFMRLALAEARAAAEAGEVPVGAVVVAGGRVVARAHNRPVALHDPTAHAEV LALRAAARELGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAGS VLDVFANPRLNHRTAVTGGVLAEECGALLREFFRARR 258 MSEEDRFMRAALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIALNDPTAHAEI LALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVES LYRLLDDRRLNHRVEAVGGVLAAECGALLSGFFRARRG 259 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTLRDRDPTAHAEMLAIRAA ARALGSERLTGCDLYVTLEPCAMCAGAISHARIARLYYGAADPKGGAVEHGPRFFAQ PTCHHRPEVYGGIGEGEAAALLRGFFRARR 260 MRAALEEARRAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCSGAILHARLDRVVYGAADPKTGAAGSVLDVFAN PRLNHHAAVTGGVLAEECGALLSGFFRARR 261 MREALAEARAAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEVLALREA ARALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAGSVLDVF ANPRLNHRTAVTGGVLADECGALLSGFFRARR 262 MRAALEEARRAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAGSVLQVFD HPRLNHRTAVTGGVLAEECGALLRDFFRARR 263 MDDDALMREALAEARAAAAAGEVPVGAVVARGGEIVARAANAPRALCDPTAHAEI LALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYAAPDPKAGACGS VLAVLNHPQLNHRVEVTAGLLADECGALLTDFFRARRG 264 MRAALEEARRAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PQLNHRVEVTGGVLAEECGALLSGFFRARR 265 MNDEDFMRAALAQAREAAAAGEVPVGAVVVCDGEIVARAHNRPIALNDPTAHAEIL ALREAARRLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVGSV LDVLNHPRLNHRVEVTRGVLAEECGALLSEFFRARRR 266 MDEEFMRRALELARQAEAAGEVPVGAVLVKDGEIVAEGWNQSIGRHDATAHAEIQV LRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVL NLFEHQAAYHYADVEHGLLEEECREQLQAFFKRRRKEKKALKQAQREAEEK 267 MSEEDRFMRAALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIALNDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVES LYRLLDDTRLNHRVEATGGVLAGECGALLSEFFRARRR 268 MSEEDRFMRAALAEARAAAEAGEVPVGAVVVAGGRIIARAHNRPIALNDPTAHAEIL ALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDAKAGAVESV LRLFDHPALNHRVEAVGGVLADECGALLSEFFRARRA 269 MREALAEARAAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAGSVLDVFA NPRLNHRTAVTGGVLADECGALLRDFFRARR 270 MNDEDYMRAALEQARQAAAAGEVPVGAVVVCGGEIVARAHNRPISASDPTAHAEIL ALREAARKLGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGAADPKAGAVGSV LDVINHPRLNHRVEVTGGVLAGECGALLSGFFRARR 271 MREALAEARAAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEVLALRAA ARELGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVFGARDPKAGAAGSVLDVFA NPRLNHRTAVTGGVLAEECGALLSGFFRARR 272 MNDEDYMRAALEQARQAAAAGEVPVGAVVVCDGKIVARAHNRPISANDPTAHAEI LALREAARQLGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGASDPKAGACGSV LNVINHPQLNHRVEVTGGVLADECGALLKDFFRARR 273 MSEEDRFMRAALAEARAAAAEGEVPVGAVVVAGGRIVARAHNRPVALNDPTAHAEI LALRAAARALGNYRLTGCTLYATVEPCAMCAGAILHARIARLVYGAADPKAGAVRS VLRVLDHPALNHRVEVTAGVLAEECAALLQEFFRARR 274 MNDEDYMRAALEQARQAAAAGEVPVGAVVVCGGEIVARAHNRPISANDPTAHAEIL ALREAARKLGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGAADPKAGACGSV LNVINHPQLNHRVEVTGGILADECGALLKDFFRARR 275 MRAALEEARRAAAAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PRLNHRVEVTSGVLAEECGALLTDFFRARR 276 MRAALEEARRAAAAGEVPVGAVVVRDGEIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGACGSVLSVFDQ PRLNHRTTVTGGVLAEECGALLSGFFRARRG 277 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEVLALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVVGGVGAAEAGALLRDFFAARR 278 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM IALTAAANYLGSKRLEGCTVYVTLEPCPMCAGALVLARVERLVFGAFDPKAGACGT LYDIVRDRRLNHRLEVVGGVLEEESAALLREFFEKRR 279 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATGHAEIM ALRAAGEKLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAARQAKRDAE 280 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGAVAHGPRLF AQPTCHHRPEVVGGVGAAEAAALLRDFFAARR 281 MDDEALMGLALDEARAAAAAGEVPIGAVVARGGEVLARAGNRTLRDCDPTAHAEI VALREAARALGNYRLTGCTLYVTLEPCAMCAGAAIQARLDRVVYGAADPKAGAAG SVLDVLGHPRLNHRPAVEGGVLAAESAALLREFFAARR 282 MREALAEARAAAAAGEVPVGAVVVRDGAVLARAGNASIRARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARLARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVTGGVGAAEAAALLRDFFAARR 283 MSDEQFMRRAIELAKKGEELGEVPVGAVLVKDGEIIAEGWNQSISTHDATAHAEIMA IRAAGEKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVL NLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAAKQAKREAEEK 284 MDDEFYMRRALELAALAEEHNEVPVGAVLVLNGEIIGEGWNRSIGHHDATAHAEIM ALRQAGKKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEIKALKKAQKEAE 285 MDDAGFMRLALAEARKAAAAGEVPVGAVVVRDGAVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAV AHGARVFDQPTCHHRPEVYGGIGAGEAAALLRDFFAARR 286 DLDDARFMREALAEARAAAEAGEVPVGAVVVADGRIVARAHNRPVALNDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDAKAGAVES LYRLLDDARLNHRVEVAAGVLADECGALLTEFFRARR 287 DESFMREALAEARAAAEAGEVPVGAVVVHGGQIVARAHNRPIELSDPTAHAEILALR AAARALGNYRLTGCTLYATLEPCAMCAGAILHARIDRVVYGASDPKAGAAGSVLSV FDHPALNHRVDVTAGVLAEECGALLREFFRARRR 288 DPDAAFMRAALAEARAAAEAGEVPVGAVVVADGAIVARAHNRPIALNDPTAHAEIL ALREAARALGNYRLTGATLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVESL YRLLDDARLNHRVAVTGGVLAAECGALLTAFFRARR 289 DERFMREALAEARAAAAAGEVPVGAVVVRDGEIVARAANRTVRDNDPTAHAEILAL REAARALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYAAADPKAGACGSVLS VMNHPQLNHRVEVESGLLAEECGALLTEFFRARRG 290 MTADEQYMRRALELARQAEAEGEVPVGAVLVKDGEIVAEGWNRSIGHHDATAHAEI QVLRKAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGT VLNLFEHQAAYHYADVEHGLLEDECREQLQAFFKRRRKEKKALKQALKESN 291 RIRSDEDFMRQALAEARAAAAAGEVPVGAVVVAGGRIVARAHNRPIDLVDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVES VLRLLDHPALNHRVEAVSGVLAGECGALLREFFRARR 292 DLDEALMREALAEARRAAEAGEVPVGAVVARGGRIVARAHNQPVALHDPTAHAEIL ALRQAAREAGNYRLEGCTLYATLEPCAMCAGALLHARVARLVYGARDPKAGAVGS LYDLLRDPRLNHRVEVTAGVLAEECGALLSGFFRARR 293 MREALAEARAAAAAGEVPVGAVVVDPAGEIVARAGNAPRALCDPTAHAEILALRAA AAAAGNYRLPGHVLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPEVTGGVLAEECGALLRDFFRARR 294 RLDEQFMRRALELAAHAEAEGEVPVGAVLVLDGQVIGEGWNRSIGQHDATAHAEIM ALRQAGQVVQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTV LNLFEHQAAYHYADVEHGLLEEECREQLQAFFKRRRKEKKALKQAQRAAE 295 DPDDVAFMREALAEAERAAAAGEVPVGAVVVHDGVIVGRGHNRPIASRDPTAHAEI VALREAAAALGNYRLTGCSLYVTIEPCAMCAGAILHARIARLVYGAADPKAGACGS VLDVFAEPRLNHHAEVTGGVLADECAALLRSFFAARR 296 DPDERFMRAALAQARAAAEAGEVPVGAVVVRDGRIVARAHNQPIALNDPTAHAEIL ALREAARELGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDAKAGAVESK LRLFENGSFNHRVEVTGGVLAGECGALLSEFFRARR 297 MDEEFMREALAEARAAAEAGEVPVGAVVVAGGRIVGRGRNRPVELADPTAHAEILA LREAARALGNYRLEGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAAGSVL DVFALPRLNHRTAVTGGVLAEECGALLSGFFRARRG 298 RSSDAALMREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPVALSDPTAHAE VLALREAARELGNYRLEGCTLYATLEPCAMCSGALLHARVARLVYGAADPKAGAV GSVLDLFANPRLNHRVEVTGGVLAEECGALLSGFFRARRG 299 DDDERWMREALAEARAAAAAGEVPVGAVVVRDGVLLARAGNASIRERDPTAHAE MLALRAAARALGNHRLGGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKAGAV DHGPRLFAQPTVHHRPEVVAGVGAEESAALLRDFFRARR 300 DPDSDEAFMRAALAEARAAAEAGEVPVGAVVVADGAIVARAHNRPIALHDPTAHAE ILALRAAARRLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGS VLAVMNHPQLNHRVEVTGGILAEECGALLRDFFRARR 301 MREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPVALHDPTAHAEILALRQA AAELGNYRLEGCTLYATLEPCAMCAGAMLHARLARVVYGAADPKAGAAGSVLDLF ANPRLNHRTEVVGGVLAEECGALLSGFFRSRR 302 DERFMREALAEARAAAAAGEVPVGAVVVRDGVVLARAGNRTLRDRDPTAHAEML ALRQAARALGSHRLTGCDLYVTLEPCAMCAGAISHARIARLYYGAADAKGGAVEHG PRFFAQPTCHHRPEVYGGIGETEAAALLRGFFRERR 303 MDSDLEFMRLALAEARAAAEAGEVPVGAVVVAGGRVVARAHNRPVALHDPTAHAE ILALRAAARELGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGS VLDVIHHPRLNHRVEVTGGVLAEECGALLSGFFRARR 304 MREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPVALHDPTAHAEILALREAA RALGNYRLEGCTLYATLEPCAMCAGALLHARVARLVYGARDPKAGAVGSVLDLLD HPRLNHRVEVVGGVLAEECGALLSGFFRARRG 305 DDRRWMREALAEARAAAEAGEVPVGAVVVRDGRLLARAGNASIRDRDPTAHAELL ALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAH GPRLFEQPTLHHRPEVTGGVLAAEAGELLRAFFRARR 306 MNDEDFMRAALAQARLAAEAGEVPVGAVVVCDGEIVARAHNRPISASDPTAHAEIL ALREAARRLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVGSV LDVLNHPRLNHRVEVTGGVLAEECGALLRDFFRARR 307 DESSDLRFMREALAEARAAAEAGEVPVGAVVVCGGRIVARAHNRPIALSDPTAHAEI LALREAARELGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGS VLDVINHPRLNHRVEVTGGVLAGECGALLSGFFRARRG 308 DDLFFMREALAEARRAAAEGEVPVGAVVVCGGRIIARAHNRPIALNDPTAHAEILAL RAAARALGNYRLTDCTLYATLEPCAMCAGAILHARIRRLVYGAADPKAGAVRSVLR LLDAPALNHRVAVTAGVLAEECGALLSEFFRARR 309 DPPSADEAFMREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIALSDPTAHA EILALRAAARALGNYRLTGTTLYATVEPCAMCAGAIVQARVARLVYGAADPKAGAV ESLFRILDHPALNHRVEVTAGVLAEECAALLREFFRARR 310 DETEAFMRAALAEARAAAEAGEVPVGAVVVADGRIVARAHNRPVALHDPTAHAEIL ALREAARRLGNYRLTGCTLYATLEPCAMCAGAVLHARLARLVYGARDAKAGAVGS VLDLLAHPRLNHRTAVTAGVLADECGALLSAFFRARRG 311 DDDERWMREALAEARAAAAAGEVPVGAVVVRDGVLLARAGNASIRDRDPTAHAE MLALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKAGAVD HGPRLFEQPTIHHRPEVTAGVLADECGALLRDFFRARR 312 DPTTDEALMREALAEARAAAEAGEVPVGAVVARDGEIVARAANAPRALCDPTAHAE ILALRAAARALGNYRLTGCTLYATLEPCAMCAGAALHARFARIVYGAADPKAGAAG SVLDVLDQPRLNHRTRVTGGVLADECGALLTEFFRARR 313 MNKDEFYMKRALELAQKAEEEGEVPVGAVLVLDDEIIGEGWNRPIGSHDATAHAEIQ ALRDAGQKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVYGAPDLKAGAAGT VLNLFEHEAAYHYADVEHGLLEDECREQLQAFFKRRRKEIKAKKEAEKKALE 314 MNSDEFYMQRALELAQKAEQEDEVPVGAVLVLDGEIIGEGWNRSIGHHDATAHAEM MALKQGGKQIQNYRLLDATLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGT VLNLFEHQAAYHYADVEQGLMEEECREQLQAFFKRRRKEKKALKQAKREAEE 315 DERFMREALAEARAAAAAGEVPVGAVVVRDGVVLARAGNRTLRDRDPTAHAEML ALRQAARALGSWRLTGCTLYVTLEPCAMCAGAMVQARVDRLVYGAADPKAGAAG SVLDVLGHPRLNHRPEVAAGVLAEECGALLREFFRERR 316 MRAALEEARRAAAEGEVPVGAVVVRDGAIVARAHNRPIALNDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSVLSVINHP RLNHRVEVTGGVLAEECGALLTGFFRARR 317 DPDAAFMREALAEARAAAAAGEVPVGAVVVRAGRIVARAHNRPVELHDPTAHAEIL ALRAAARELGNYRLTGCTLYATLEPCAMCAGAILHARIERLVYGARDAKAGAAGSV LDVFANPRLNHRVAVEGGVLADECAALLREFFRARR 318 MDDEALMRVALEEARAAAAAGEVPVGAVVARGGEIVARAANAPIAASDPTAHAEIL ALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYAAPDPKAGACGSV LAVLDHPALNHRVEVTGGVLAEECGALLREFFRARR 319 MSDEQYMRRALELARQAEQEGEVPVGAVLVKDGEIIAEGWNRSIGHHDATAHAEM QVLRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGT VLNLFEHQAAYHYADVEHGLLEEECREQLQAFFKRRRKEIKARKQAEKEAEAR 320 DPLEQDERWMREALAEARAAAEAGEVPVGAVLVRDGVLLARAGNRTIRDRDPTAH AEMLALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKGGA VAHGPRLFEQPTLHHRPEVTGGVLAEEAGELLRAFFRARR 321 MREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNQPIALNDPTAHAEVLALRQA ARELGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAGSVLDVFA NPRLNHHAQVTGGVLAEECGALLSGFFRARR 322 DDLSFMREALAEAEAAAEAGEVPVGAVLVRDGEIVARGRNRVIEDRDPTAHAEIVAL REAGRALGNYRLEGCTLYVTLEPCAMCAGALVHARLDRLVYGAADPKAGAAGSVL DVLNHPRLNHRMEVTGGVLADECGAMLRAFFRARR 323 DRLRADEQFMRAALAEARAAAAAGEVPVGAVVVRDGEIVARAHNRPIALHDPTAH AEILALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGA CGSVLSVMNHPRLNHRVEVTGGVLADECGALLTEFFRARR 324 MREALAEARAAAAAGEVPVGAVVVRGGEIVARAHNRPVALSDPTAHAEVLALREA ARRLGNYRLEGCTLYATLEPCAMCSGAVLHARLARLVYGAPDPKAGAAGSVLDVL DHPRLNHRTAVTGGVLAEECGALLSGFFRARRG 325 DDRRWMREALAEARAAGAAGEVPVGAVVVRDGELLARAGNASIRDRDPTAHAEML ALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKGGAVAHG PRLFEQPTLHHRPEVTAGVLADECGALLRDFFRARR 326 MREALAEARRAAEAGEVPVGAVVVRDGEIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAPDPKAGACGSVLSVFDQ PRLNHRTRVEGGVLAEECGALLSGFFRARR 327 DDRDRRWMRAALAEARAAAEAGEVPVGAVVVRDGELLARAGNASIRDRDPTAHAE MLALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAV AHGPRLFEQPTLHHRPEVTAGVLAEEAGELLRAFFRARR 328 MREALAEARAAAAAGEVPVGAVVVRGGEIVARAHNRPIALNDPTAHAEILALREAA RVLGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PQLNHRVEVTSGVLAEECGALLTDFFRARR 329 MREALAEARAAAEAGEVPVGAVVVRDGEIVARAHNRPIALNDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARLARLVYGAADPKAGACGSVLSVINH PRLNHRVEVTSGVLADECGALLSDFFRARRRAA 330 DDRFMRAALAEARAAAEAGEVPVGAVVVVDGRIVARAHNRPVELSDPTAHAEVLA LREAARALGNYRLEGATLYATLEPCAMCSGAILHARVERVVYGAADSRAGAAGSVL DVFATRRLNHQTTVTGGVLAEECGALLSGFFRARR 331 DDDQRFMREALAEARAAAAAGEVPIGAVVVCDGAIVARAGNRTIRDNDPTAHAEIL ALRQAARALGNYRLTGCTLYVTLEPCAMCAGAIVQARIARLVYGAADPKAGAVDSV LDVLNHPRLNHRVEVTRGVLAEECGALLRDFFRARR 332 MSDDERFMRLALEQARLAAEAGEVPVGAVVVCDGRVVARAHNRPIALNDPTAHAEI LALREAARELGNYRLTGCTLYATLEPCAMCSGAVLHARLARVVYGAADPKTGAAGS VLDLFAEPRLNHHAEVTGGVLAGECGALLSGFFRARRG 333 DPTDLAFMREALAEAEAAAAAGEVPVGAVVVHEGRIVGRGRNRMIAASDPTAHAEI VALREAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIARLVYGAADPKAGACGS VLDVLNHPRLNHRTEVTAGVLAEECGAMLSGFFRARRAQQRAARVAAS 334 DPPDAVEMRAALEEARAAAEAGEVPVGAVLVHDGQILARAGNRTIRDRDPTAHAEIL ALRQAARVLGSHRLTGATLYVTLEPCAMCAGAISHARIARLVYGADDPKGGAVRHG PRFFEQPTCHHRPEVTGGILAEESAALLRGFFRARR 335 MRAALEEARRAAEAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGACGSVLSVFDQ PRLNHRTRVEGGVLAEECGALLSGFFRARR 336 DDDQRFMALALAQAQAAADAGEVPVGAVVVCDGRVVARAHNRPIALNDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVES LYRLLDDDRLNHRVAVTGGVLAAACGALLSGFFRARRR 337 DLTDEQLMRAALAEARAAAAAGEVPVGAVVAKDGEIIARAHNRPIAAHDPTAHAEIL ALRAAARALGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGAADPKAGACGSV LAVMNHPQLNHRVEVTGGVLAEECGALLRDFFRARR 338 DDDERWMREALAEARAAAEAGEVPVGAVVVRDGELLARAGNASIRDRDPTAHAEM LALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKGGAVAH GPRLFEQPTLHHRPEVTGGVLAEEAGALLRAFFRARR 339 DLEFMREALAEARAAAEAGEVPVGAVVVRDGAIVARAGNRTLRDRDPTAHAEMLA LRQAARALDSWRLSGCTLYVTLEPCAMCAGAMVQARLDRLVYGAADPKAGAAGS VLDVLGHPRLNHRVEVTGGVLAEECGALLREFFRARR 340 RSESDEALMREALAEARRAADAGEVPVGAVVVRDGAILARAGNAPIAASDPTAHAEI LALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVES VLDLLDRPALNHRVEVTGGVLAAECGALLSGFFRARR 341 MDDAGFMRAALAEARAAAEAGEVPVGAVVVCDGRIVARAGNRTLRDRDPTAHAE MLALRAAARALGSHRLTGCDLYVTLEPCAMCAGAISHARIRRLYYGASDPKGGAVE NGVRFFAQPTCHHAPEVYGGIGEAEAAALLRGFFRARR 342 MRDEDYMRAALAQAREAAAAGEVPVGAVVVADGRIVARAHNRPIALNDPTAHAEI LALREAARQLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVGS VLDVLNHPRLNHRVEVTSGVLAAECGALLTEFFRSRRR 343 DETEAFMRAALAEARAAAAEGEVPVGAVVVADGAIVARAHNRPIALNDPTAHAEIL ALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVESL YRLLDDTRLNHRVEAVGGVLADECGALLTEFFRARRG 344 DDDERWMREALAEARAAAAAGEVPVGAVVVRDGVLLARAGNASIRDRDPTAHAE MLALRAAARALGNHRLGGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKAGAV DHGPRLFEQPTCHHRPEVVSGVGAAESAALLRDFFRARR 345 MRAALEEARRAAEAGEVPVGAVVVRDGAIVARAHNRPIALNDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGACGSVLSVFDQ PRLNHRTTLTGGVLAEECGALLSGFFRARRRAA 346 MDDDLFMRAALDEARAAAEAGEVPVGAVVVADGRIVARAHNRPIALNDPTAHAEIL ALRAAAAALGNYRLTGCELFVTLEPCAMCAGAILHARLARVVYGAADPKTGAAGSV LDVFANPRLNHRTEVRGGVLADECGALLTEFFRARRG 347 MDDEALMREALAEARAAAEAGEVPVGAVVARGGEIVARGRNRMIADGDPTAHAEI VALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYAAPDPKAGACGS VLSVMNHPQLNHRVEVASGLLAEECGALLTNFFRARRG 348 DPEDERFMREALAEAERAREAGEVPVGAVVVLDGRIVGRGHNRPIGAHDPTAHAEIV ALREAAAALGNYRLTGATLYVTLEPCAMCAGAILHARIARLVYGAADPKTGAVGSL LDLLAEPRLNHRTEVTGGVLAEECGALLSAFFRARR 349 DDLSFMREALAEAEAAAAAGEVPVGAVVVHGGRIVGRGRNRMIADHDPTAHAEIVA LREAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIERLVYGAADPKAGACGSVLS VMNHPQLNHRVEVTSGVLADECGAMLSGFFRARR 350 DLEFMRLALEEARAAAAAGEVPVGAVLVRDGEVLARAGNRTIRDRDPTAHAEMLAI REAARRLDNYRLEGTTLYVTLEPCAMCSGAILHARVPRVVYGAADPKAGAAGSVLD VLGHPRLNHRTEVVGGVLAEECGALLREFFRARR 351 DDDHFMREALAEARRAADAGEVPVGAVVVRAGQIIARAHNRPVALHDPTAHAEILA LRAAARRLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSVL DVLNHPRLNHRVEVTAGVLAEECGALLSAFFRARR 352 DDDQRFMREALAEARAAAAAGEVPIGAVVVCDGEIVARAGNRTIRDNDPTAHAEIL ALRQAARALGNYRLTGCTLYVTLEPCAMCAGAIVHARIARLVYGAADPKAGAVNSV FDLLNHPRLNHRVEVTSGVLADECGALLRDFFRARR 353 DESFMREALAEARAAAEAGEVPVGAVVVHGGRIVARAHNRPIELSDPTAHAEILALR AAARALGNYRLTGCTLYATLEPCAMCAGAILHARIDRVVYGAADPKAGAAGSVLDV FANPRLNHHARVTGGVLADECGALLSGFFRARR 354 DPESDAAFMRAALAEAQAAAEAGEVPVGAVVVCDGRIVARAHNRPIGLNDPTAHAE ILALREAARELGNYRLTGCTLYVTLEPCAMCSGAILHARLARVVYGAADPKTGAAGS VLDLFANRRLNHQTQVEGGVLAEECGALLSGFFRARRG 355 MREALAEARAAAAAGEVPVGAVVVRGGEIVARAHNRPIALNDPTAHAEILALREAA RVLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSVLSVMNH PQLNHRVEVTGGVLAGECGALLSDFFRARR 356 MSDDERFMRLALAQAREAAAEGEVPVGAVVVCGGRVVARAHNRPIALNDPTAHAE VLALRAAARELGNYRLTGCTLYATLEPCAMCAGAILHARIARVVYGARDPKAGAAG SVLDVFANPRLNHHATVTGGVLAEECGALLSDFFRARRR 357 MDDDERWMREALAEARAAAEAGEVPVGAVVVRDGVLLARAGNASIRDRDPTAHA EMLALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKAGA VDHGPRLFEQPTCHHRPEVVSGVGAAESAALLRDFFRARR 358 DDDERWMRAALAEARAAAEAGEVPVGAVVVAGGRLVARAGNASIRDSDPTAHAEI LALRAAARALGNHRLAGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKGGAVAH GPRLFEQPTLHHRPEVTGGVLAAEAGALLRAFFRARR 359 MREALAEARRAAAEGEVPVGAVVVRDGAVIARAHNRPIALRDPTAHAEILALREAA RLLGNYRLTGCTLYVTLEPCAMCAGAIVHARIDRLVYGAADPKAGAVESVLRVLDH PRLNHRVEVTRGVLAEECGALLREFFRARR 360 MNDEDFMRAALAQAREAAAAGEVPVGAVVVCGGRIVARAHNRPISARDPTAHAEIL ALRAAARELGNYRLTGCELYVTLEPCAMCAGAILHARIARLVYGAADPKTGAAGSV LDVFANPRLNHRTEVTGGVLADECGALLSGFFRARRG 361 DDDQRFMAAALEEARAAAAEGEVPVGAVVVAGGRIVARAHNRPIALNDPTAHAEIL ALRAAARELGNYRLTGCTLYATLEPCAMCAGAILHARIDRVVYGARDPKAGAAGSV LDVFANPRLNHHAEVTGGVLAEECGALLSDFFRARR 362 MREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIALHDPTAHAEILALREAA RELGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSVLAVMNH PQLNHRVEVVGGVLAEECGALLREFFRARR 363 MDSDLEFMREALAEARAAAEAGEVPVGAVVVRDGEIVARAANRTIRDGDPTAHAE MVALRAAARALGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRVVYGAADPKAGA AGSVLDVLGHPALNHRTAVTAGVLAEECGALLRDFFRARR 364 DPTTDEALMREALAEARAAAADGEVPVGAVVARDGVIVARAHNAPVALSDPTAHA EILALREAARAAGNYRLPGCTLYATLEPCAMCCGAALHARLARVVYGARDPKAGAA GSVLDLLDDPRLNHRAEVVGGVLAEECGALLSGFFRARR 365 DPLSADDARFMRLALAEARAAAEAGEVPVGAVVVAGGRVVARAHNRPVALHDPTA HAEILALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAG ACGSVLAVMNHPQLNHRVEVTGGVLAEECGALLRDFFRARR 366 MNDEDFMRAALAQAREAAAAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAEIL ALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVGSV LDVMNHPRLNHRVEVTSGVLAEECGALLKEFFRARR 367 DDDQRFMREALAEARAAAEAGEVPIGAVVVCDGEIVARAGNRTIRDNDPTAHAEILA LRQAARRLGNYRLTGCTLYVTLEPCAMCAGAIVQARIARLVYGAADPKAGAVDSVL QVLNHPRLNHRVEVTRGVLAEECGALLRDFFRARR 368 MREALAEARRAAEAGEVPVGAVVVRDGEIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAPDPKAGACGSVLSVFDQ PALNHRVAVTGGVLAEECGALLREFFRARR 369 DPDARFMREALAEAEAAAAAGEVPVGAVVVAGGRIVARAHNRPVELSDPTAHAEIL ALREAARELGNYRLEGCTLYATLEPCAMCSGAILHARLARVVYGAADPKAGAAGSV LDVFALPQLNHRTAVTGGVLADECGALLSGFFRARR 370 MNDEDYMRAALEQARLAASEGEVPVGAVVVCDGKIVARAHNRPIALNDPTAHAEIL ALREAARKLGNYRLTGCTLYATLEPCAMCSGAILHARIARLVYGAADPKAGAVGSV LDVINHPRLNHRVEVTSGVLAEECGALLSGFFRARRK 371 MRAALEEARRAAEAGEVPVGAVVVRDGAIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PRLNHRVEVERGVLAEECGALLTGFFRARR 372 MSTEDERFMRLALAEARRAAAEGEVPVGAVVVAGGEVVAAAHNRPIALADPTAHA EILALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVE SVLRLLDAPGLNHRVAVTGGVLAEECGALLREFFRARR 373 MREALAEARAAAEAGEVPVGAVVVRDGAIVARAHNRPIALNDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAGSVLQVFD HPRLNHRTAVTGGVLAAECGALLSGFFRARRG 374 MREALAEARAAAAAGEVPVGAVVVRGGEIVARAHNRPIALNDPTAHAEILALREAA RALGNYRLTGCTLYATLEPCAMCAGAILHARIDRVVFGARDPKAGAAGSVLDVFAN PRLNHHAEVVGGVLADECGALLSGFFRARRG 375 DERFMREALAEARAAAAAGEVPVGAVVVRDGVVLARAGNRTLRDRDPTAHAEML ALRQAARALGSWRLAGCTLYVTLEPCAMCAGAMVLARVDRLVYGAADPKAGAAG SVLDVLGEPRLNHRPEVAAGVLAEECGELLRAFFRERR 376 DPTSDEAFMRAALAEARAAAEAGEVPVGAVVVCGGRIVARAGNRPIAARDPTAHAE ILALRAAARELGSYRLTGATLYVTLEPCAMCAGAILHARIERLVFGAADPKTGAAGS VLDLFAEPRLNHRTAVEGGVLAEECGALLRDFFRARRG 377 DPSPDEAFMRAALAEARAAAEAGEVPVGAVVVRDGRIVARAGNRPIALHDPTAHAEI LALRAAARELGNYRLTGCELYVTLEPCAMCAGAILHARLARLVYGAADPKTGAAGS VLDVFANRRLNHHTAVTGGVLADECGALLAGFFRARR 378 MDDAAFMRAALAEARAAAEAGEVPVGAVVVADGAIVARAHNRPIALNDPTAHAEIL ALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVESL YRLLDDTRLNHRVAVTGGVLADECGALLTEFFRARRR 379 DPESDAAFMRAALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIGLNDPTAHAE ILALRAAARALGNYRLTGCTLYVTLEPCAMCAGAILHARLDRVVYGAADPKTGAAG SVLDLFAQPRLNHHARVEGGVLADECGALLRDFFRARR 380 DPDAAFMRAALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIELNDPTAHAEIL ALRQAAAALGNYRLEGCTLYVTLEPCAMCAGAILHARLARVVYGAADPKTGAAGS VLDLFANPRLNHHAEVTGGVLAEECGALLRDFFRARRG 381 MREALAEARRAAEAGEVPVGAVVVRDGEIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PRLNHRVEVESGLLAGECGALLTEFFRRRRAAARG 382 MSTDLAFMREALAEARAAAEAGEVPVGAVVVRDGAILARAGNRTLRDGDPTAHAE MVALRAAAAALGSERLTDCDLYVTLEPCAMCAGAISHARIRRLYYGAADPKGGAVE HGVRFFASPTCHHRPEVYGGIGEGEAAALLRDFFRARR 383 DDRFMREALAEARAAAAAGEVPVGAVVVRDGEIIARAGNRTLRDRDPTAHAEMLAL RQAARALGSHRLTGCDLYVTLEPCAMCAGAIQHARIRRLVYGAADPKAGAVDHGV RLFDSPSCHHRPEVVAGVGEGEAAALLRDFFRERR 384 MREALAEARAAAAAGEVPVGAVVVRGGEIVARAHNRPIALHDPTAHAEILALREAA RALGNYRLEGCTLYATLEPCAMCSGAILHARLARLVYGAADPKAGAVGSVLDVIGN PRLNHRVEVTGGVLAEECGALLSGFFRARR 385 MDDAGFMRAALAEARAAAAAGEVPVGAVVVRDGAIVARAGNRTLRDRDPTAHAE MLAIRAAARALGSERLTGCDLYVTLEPCAMCAGAISFARIRRLYYGAADPKGGAVEN GVRFFASPTCHHAPEVYSGIGEAEAAALLRDFFRARR 386 RPPSDDERWMAEALAQARAAAAEGEVPVGAVVVRDGRLLARAHNRPIALNDPTAH AEILALRAAAREIGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAC GSVLDVLNHPRLNHRVEVTGGLLADECGALLSAFFRARR 387 DLEFMREALAEARAAAEAGEVPVGAVVVAGGRIVARAHNRPIELHDPTAHAEILALR QAATALGNYRLTGCTLYATLEPCPMCAGAALHARLDRIVYGAADPKAGAAGSVLDL FADTRLNHHAAVAGGVLADECGALLSGFFRARR 388 DDDERWMRAALAEARAAAAAGEVPVGAVVVRDGELLARAGNASIRERDPTAHAEL LALRAAARRLGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAH GPRLFEQPTLHHRPEVTAGVLAEECGALLREFFRARR 389 MREALAEARAAAAAGEVPVGAVVVRGGEIVARAHNRPIALHDPTAHAEILALREAA RRLGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGACGSVLSVMNH PQLNHRVEVTSGVLAEECGALLTGFFRERR 390 DERWMREALAEARAAAAEGEVPVGAVVVRDGRLLARAGNASIRSRDPTAHAEILAL RRAARRLGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGASDPKGGAVAHGPR LFEQPTCHHRPEVTGGVLAEECGALLREFFRARR 391 MDDAGFMRAALAEARAAAEAGEVPVGAVVVADGRIVARAHNRPVALNDPTAHAEI LALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARLDRVVYGAADPKAGAAG SVLDVFANPRLNHRTAVTGGVLADECGALLTGFFRARR 392 DDRFMRAALAEARAAAEAGEVPVGAVVVCGGRIVARAHNRPIDLCDPTAHAEILAL REAARELGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDEKAGAVESLYR LLDDTRLNHRVAVTGGVLAAECGALLSEFFRARRA 393 DPDAAFMRAALAEARAAAEAGEVPVGAVVVHEGRIVARAHNRPVALNDPTAHAEIL ALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGARDPKAGAVESL YRLLDDTRLNHRVEAVGGVLADECGALLSEFFRARRR 394 DDRFMRAALAEARAAAAAGEVPVGAVVVAGGRIVARAHNQPVALVDPTAHAEVLA LRAAARELGNYRLTGCTLYATLEPCAMCAGAILHARIDRLVYGAADPKAGAVGSVL DVFANPRLNHRTRVTGGVLAAECGALLSEFFRARRR 395 MTSAPAPSDLDFMRLALAEARLAAAEGEVPVGAVVVCDGEVVARAHNRPIALHDPT AHAEILALREAARKLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAG AVESRLRLLDAPFLNHRVEVTGGVLAEECGALLKDFFRARR 396 DDRFMRAALAEARAAAEAGEVPVGAVVVCGGEIVARAHNRPIALNDPTAHAEILAL REAARRLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGAVESLYR LLDDTRLNHRVEAVGGVLAGECGALLSEFFRARRA 397 MREALAEARAAAAAGEVPVGAVVVAAGRIVARAHNRPVELSDPTAHAEILALREAA RELGNYRLEGCTLYATLEPCAMCAGALLHARLARLVYGAADPKAGAVGSVLDVLD HPRLNHRVEVTAGVLAEECGALLRDFFRARR 398 MDEEFMREALAEARAAAEAGEVPVGAVVVAGGRIVGRGRNRPVELADPTAHAEILA LREAAAALGNYRLEGCTLYATLEPCAMCAGAILHARIARVVYGARDPKAGAAGSVL DVFALPRLNHHTRVTGGVLAEECGALLSGFFRARR 399 RLDEQFMRRALELAAHAEAEGEVPVGAVLVLDGQVIGEGWNRSIGHHDATAHAEM MAIEQAGKAVENYRLLDATLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGT VLNLFEHQAAYHYADVEHGLLEEECREQLQAFFKRRRKEKKALKQAQRDAEEK 400 MSTSEADLTFMREALAEARAAAEAGEVPVGAVVVAGGEIVARAHNRPIALHDPTAH AEILALRAAARRLGNYRLTGCTLYVTLEPCAMCAGAILHARLARLVYGAADPKTGA AGSVLDLFANRRLNHHTEVTGGVLADECGALLSDFFRARRA 401 MDDAGFMRLALAEARRAAEAGEVPVGAVVVRGGEVLAAAGNRTVRDCDPTAHAE VVALREAARKLGNHRLTGCDLYVTIEPCAMCAGAISHARIARLYYGADDPKGGAVE HGPRFFGQPTCHHRPEVYGGIGAAEAAELLRGFFRARR 402 MREALAEARAAAEAGEVPVGAVVVRDGEIIARARNRMVADCDPTAHAEIVALREAA RALGNHRLGGCTLYVTLEPCAMCAGAMIHARVDRLVYGAADPKAGAAGSVLDVIN HPRLNHRMEVESGVLADECGALLKEFFRSRR 403 MDAALAEARAAADAGEVPVGAVVVRDGAVLARAGNRTLRDSDPTAHAEIVALRAA ARALGNHRLPGCTLYVTLEPCAMCAGAISHARLARLHYGAADPKGGAVEHGPRFFA QPTCHHRPDVVGGLGETEAADLLRAFFAARR 404 MSDEQYMRRALELARQAEQQGEVPVGAVLVRDGEVIAEGWNQSISSHDATAHAEIM ALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAQRDAKRAADE 405 MDAALAEARAAADAGEVPVGAVVVRDGVVLARAGNRTVRDADPTAHAEIVALRA AARALGNHRLPGCTLYVTLEPCAMCAGAISHARLARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVTGGVGAAEAAALLRAFFAARR 406 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRDGEVLAAAGNRTLRDRDPTAHAE VVALRAAARALGSERLPGCDLYVTLEPCAMCAGAISFARIRRLYFGAGDPKGGAVEH GPRFFAQPTCHHAPEVYGGLGEGEAAGLLRGFFAARR 407 MRSALDEARRAAAAGEVPVGAVVVRDGAVLAAAGNRTVRDCDPTAHAEIVALRAA AAALGNYRLDGCDLYVTLEPCAMCAGAMVHARLARLVYGAADPRAGAAGSVLDV VRHPALNHRMEVTGGVLADECGALLREFFAARR 408 MDSAAKDLCYMRRALELAALAEAEGEVPVGAVLVKDGEIVGEGWNRSIGSHDATA HAEIMALRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAG AAGTVLNLFESQASYHYAEVESGLLEQECREQLQAFFKRRRKEIKALRQAEKEAQQK 409 MDSAAKDLCYMRRALELAALAEAEGEVPVGAVLVKDGEIVGEGWNRSIGSHDATA HAEIMALRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAG AAGTVLNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKAQRDAKRAAD 410 MTSAPEHEKYMRRALELARQAEEHGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAH AEIMALRAAGKALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGA AGTVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKQAKREQEE 411 DTEFMREALAEARAAAAAGEVPVGAVVVHEGKIIARAGNRTIRDNDPTAHAEIVALR AAARALGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGADDPKAGAAGSVLN VLNHPRLNHQMQVESGVLADECAALLQDFFRARR 412 MTDADFMALALEEARAAAALGEVPVGAVVVRDGAVIARAGNRTVRDNDPTAHAEI VALREAARALGNYRLDGCTLYVTLEPCAMCSGAMLHARLARVVYGAADPKTGAAG SVLDLFATAQLNHQTQVQGGVLAAECGALLQDFFRQRR 413 DESYMRRALELARQAEQHGEVPVGAVLVKDGEVIAEGWNQSIGSHDATAHAEIMAL RAAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVLN LFESQASYHYAEVEGGLLEDECREQLQAFFKRRRKEIKAARQAKRAAE 414 MDEALAEARRAAAAGEVPVGAVLVRDGRVLARGGNRTIRDCDPTAHAEIVALREAA RAAGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPRAGAAGSVFDVLR HPALNHRMEVEGGVRAEECGALLREFFRARRA 415 MTEADLRFMQLALEEARRAGEAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHA EIVALREAARALGNYRLDGCTLYVTLEPCAMCAGAMIHARLDRLVYGADDPRAGAA GSVLDVLGHPALNHQTRVTAGVLAEECGALLREFFRARR 416 MTDEEYMRRALELARQAEQQGEVPVGAVLVKDGEVIAEGWNQSIGSHDATAHAEI MALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKQAKRDAEE 417 MRDALAEARAAAARGEVPVGAVVVRDGAVLARAGNASIAARDPTAHAEILALRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVAHGPRFFA QPTCHHRPEVAGGLGEAEAAALLRDFFRARR 418 MTDEDFMRLALAEAQAAAAAGEAPIGAVLVRDGQVLARGQNRVIRDNDPTAHAEIV ALREAARQLGNYRLDGCELYVTLEPCAMCAGAMIHARLARLVYGAADPKAGAAGS VLDVINHPRLNHRMQVTAGVLADECGALLRDFFRQRR 419 MRAALDEARAAADAGEVPVGAVVVRDGAILARAGNRTVRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVTGGVLADEAGELLRAFFAARR 420 DETYMRRALELARQAEQHGEVPVGAVLVKDGEVIAEGWNQSIGAHDATAHAEIMA LRAAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVL NLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKAARQAARDAQ 421 MNDEFYMRRALELAKMAEERGEVPVGAVLVRDGEVIAEGWNQSIGSHDATAHAEI MALRAAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALKQAQREAEEK 422 DTSPADLRFMRLALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTLRDRDPTAH AEIVALRAAARALGSHRLGGCTLYVTLEPCAMCAGAIAQARVARLVYGADDPKGGA VAHGPRLFAQPTCHHRPEVVGGVGAEEAAALLRDFFAARR 423 MTAADERFMRRAIELAAQAEAAGEVPVGAVLVKDGEIVAEGWNQSIGSHDATAHAE IQTLRQAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVEGGLLEDECREQLQAFFKRRRKEIKAARQAAKEAE 424 MDDDGLMRAAIAEAEAAAAAGEVPVGAVLVRDGVVLARGRNRMIADSDPTAHAEI VALREAARALGNYRLEGCELYVTLEPCAMCAGAMVHARLARLVYGAADPKAGAA GSVLDVLGHPRLNHRMEVTGGVLADECGAMLRDFFRARRA 425 DDTFYMRRALELAALAESEGEVPVGAVLVKDGEIIAEGWNRSIGSHDATAHAEIETL RKAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGTVLN LFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAEKAAQE 426 MDDAGFMREALAEARAAAAAGEVPVGAVVVKDGEIIARAGNRTIRDCDPTAHAEIV ALRAAAQALGNYRLDGCTLYVTLEPCAMCSGAMLHARLPRVVYGAADPKTGAAGS VLDLFAEPRLNHHTRVEGGVLAAECGALLTDFFRARRG 427 MDAALEEARRAAAAGEVPVGAVLVRDGVVLARAGNRTVRDCDPTAHAEIVALRAA AAALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVFDVL GSPRLNHRVEVEGGVRAAECGALLQDFFRARRAG 428 MTDDERWMAEALREAEAAAAEGEVPVGAVVVRDGELIARGRNRVVRDCDPTAHAE IVALREAARALGNYRLTGCTLYVTLEPCAMCAGAMVHARLDRLVYGAADPKAGAA GSVLAVLNHPRLNHQMEVAGGVLAGESAALLRDFFRARR 429 DSEFMAEALAEARAAAEAGEVPIGAVVVCDGEIVARAGNRTIRDNDPTAHAEIVALR EAAAKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPKAGAAGSVLD VLGHPQLNHQTEVEGGVLAEECGALLKDFFASRR 430 DPEYMRRALELAAQAEAEGEVPVGAVLVKDGEVVAEGWNRSIGDHDATAHAEIQV LRKAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVL NLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKAARKAAKEAE 431 DTEMMRLALAEARAAAEAGEVPVGAVVVRDGVVLARAGNRTVRDNDPTAHAEIVA LREAARALGNHRLEGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHG PRLFEQPTTHHRPEVTGGVLAEEAGALLREFFAARR 432 MTDADFMALALEEARAAAALGEVPVGAVVVRDGAVVARAGNRTVRDCDPTAHAE VVALREAARVLGNYRVDGATLYVTLEPCAMCAGAMIHARLPRLVYGAADPRAGAA GSVLDVLGHPALNHRVEVTGGVLADESAALLREFFRERR 433 DEPLDRDRYFMEIALAEARAAAAAGEVPVGAVVVRDGEVIARAGNRTVRDNDPTAH AEIVALREAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGA VAHGPRFFEQPTCHHRPEVTGGVLAAESAALLRGFFAARR 434 MTSDAEFMALALEEARAAAALGEVPVGAVVVRDGAVIARAGNRTIRDCDPTAHAE MVALREAARALGNYRLAGCDLYVTLEPCAMCAGAIVHARLARLVYGAADPKTGAA GSVFDVLGSGRLNHRPEVVAGVLADECGALLTDFFRARR 435 MTEEDKYFMQRAIELAKLAEENGEVPVGAVLVKDGEIIAEGWNQSIGNHDATAHAEI MTLRQAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKQQKLEQE 436 MSAALDEARRAAAAGEVPVGAVVVRDGVVLAAAGNRTLRDCDPTAHAEIVALRAA ARALGNYRLDGCDLYVTLEPCAMCAGAMIHARLARLVYGAADPKTGAAGSVLDVL GHPRLNHRTAVTGGVLADECGALLRDFFAARR 437 DTSERDERFMRLALEEARAAAEAGEAPIGAVVVRDGAVLARAGNRTVRDNDPTAHA EVVALREAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGA VAHGPRFFAQPTCHHRPEVTGGVLAEESAELLRGFFRARR 438 DPDSRFMQAALAEARAAAEAGEVPIGAVVVRDGEIVARAGNRTIRDNDPTAHAEIVA LREAARVLGNYRLTGCTLYVTLEPCAMCAGAMIHARIDRLVYGAADPKAGAAGSVL DVLNHPKLNHQMEVEAGVLADECGALLRDFFRARR 439 MDDDERWMRLALEEARLAEEAGEVPVGAVVVRDGELLARGRNRVLRDCDPTAHAE IVALREAARRLGNYRLDGCTLYATLEPCAMCAGAMVHARLARLVYGAPDPKAGAA GSVLDVLNHPRLNHRMEVTAGVLAEECGALLRRFFQARR 440 MSAALAEARRAAAAGEVPVGAVVVRDGAVLAAAGNRTVRDCDPTAHAEIVALRAA ARALGNHRLEGCTLYVTLEPCAMCAGAIAQARVARLVYGAADPKGGAVAHGPRLF AQPTCHHRPEVVGGVGEAEAAALLRDFFAARR 441 MRSALALAAAAGAAGEVPVGAVVVRDGVVIGRGENRVIRDSDPTAHAEIVALRDAA RALGNYRLTGCTLYVTLEPCAMCAGAMIHARIDRLVYGAADPKAGAAGSVLDVLN HPQLNHQMEVEGGVLAEECGALLRDFFRARR 442 RTADERWMRLALEEARAAEAAGEVPVGAVVVRDGELIARGRNRVLRDCDPTAHAEI VALREAARALGNYRVEGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPRAGAAG SVLDVLGHPALNHQTQVTGGVLAEECGALLREFFRARRG 443 DDLSFMQEALAEARAAAEAGEVPIGAVVVRDGAILARAGNRTVRDNDPTAHAEIVA LREAARALGNYRLAGCTLYVTLEPCAMCAGAMIHARVDRLVYGAADPKAGAAGSV LDVLGHPRLNHRMEVEGGVLAEECGALLREFFRARR 444 MSSDAGFMAEALAEAEAAAAAGEVPVGAVVVCGGEIVARAGNRTIRDCDPTAHAE MVALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPKAGAA GSVLDVINHPRLNHQMEVEAGVLADECGAMLRRFFQERR 445 MDDDRWMRLALEEARRAEEEGEVPVGAVVVLGGEVIGRGRNRVIRDSDPTAHAEIV ALREAARTLGNYRLDGCELYVTLEPCAMCAGAMVHARLARLVYGAADPRAGAAGS VLDVLGHPRLNHRMEVTGGVLAEECGALLRDFFRRRR 446 MDDAGFMREALAEAEAAAAAGEVPVGAVVVCDGRIVARAGNRTVRDNDPTAHAEI VALREAARALGNHRLGGCTLYVTLEPCAMCAGAMIHARIDRLVYGADDPKAGAVR SVLQVLDHPRLNHRMAVESGVLAGECAAVLQAFFAARR 447 MDAALEEARRAAAAGEVPVGAVLVRDGEVLARGGNRTIRDCDPTAHAEIVALRAAA RAAGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPRAGAAGSVFDVLR HPALNHRMEVEGGVLAEESAALLRGFFRARR 448 MRDALALARAAAAAGEVPVGAVVVKDGVVVGRGENRVVRDSDPTAHAEIVAMRE AARALGNYRLTGCTLYVTLEPCAMCAGAMIHARLDRVVYGAADPKTGAAGSVLDV LGHPRLNHQTQVEGGVLAAECGALLSDFFRARR 449 MDDAGFMREALAEAEAAAAAGEVPVGAVVVKDGEIIARAGNRTVRDCDPTAHAEIV ALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGADDPKAGAAGS VLNVLNHPRLNHQMQVEAGVLAEECGAMLRRFFETRR 450 MDDAAFMGEALAEARAAAAAGEVPIGAVVVCDGEIVARAGNRTVRDNDPTAHAEI VALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARVDRLVYGADDPKAGAAR SVLNVVDHPALNHRLEVTSGVLAAECAELLRGFFERRR 451 MTAADAAAMRAALAEARAAAARGEVPVGAVVMRDGVIVARAGNATVAGHDPTAH AEIVALRRAARALGNHRLTGCALYVTLEPCAMCAGAIAHARIARLVYGAADPKGGA VAHGPRFFAQPTCHHRPEVTGGVLAEEAGALLRAFFRARR 452 DTEMMALALAEARAAAEAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEIVA LREAARRLGNYRLPGCTLYVTLEPCAMCAGAIMHARLDRVVYGAADPKTGAAGSV LDLFAEPRLNHHTAVVGGVLADEAGALLRGFFAARR 453 MTEEDKYFMKRAIELAKLAEENGEVPVGAVLVKDGEIISEGWNQSIGNNDATAHAEI MALREAGKVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEKKELKKLKREEN 454 MDSAAKDLCYMRRALELAALAEAEGEVPVGAVLVKDGEIVGEGWNRSIGSHDATA HAEIMALRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAG AAGTVLNLFESQASYHYADVESGLLEEECRAQLQAFFKRRRKEIKAQRDAQRAAQE K 455 MRTALEEARRAAEAGEVPVGAVVVRDGVVLARAHNRTVADHDPTAHAEILALREA ARVLGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRLVYGAADPKAGAAGSVLDVL GHPRLNHRPEVAAGVLAEECGELLRGFFRERR 456 DDDERWMREALAEARAAEEAGEVPVGAVVVRDGELVGRGRNRVLRDSDPTAHAEI VALREAARALGNYRLDGCTLYATLEPCAMCAGAMLHARLARLVYGAADPKAGAA GSVLDVLNHPRLNHRMEVTGGVLAEECGALLRGFFRARRG 457 RSSPDERFMALALAEARRAAEAGEVPVGAVLVRDGAVLAAAGNRTIRDNDPTAHAE IVVLREAARRLGNYRLEGCTLYVTLEPCAMCAGAMVNARLGRLVYGAADPRAGAA GSVLDVLRHPALNHRMEVTGGVLAAECGALLRDFFAARR 458 MRDALAEARKAAALGEVPVGAVVVKDGAVIARGHNRTVADSDPTAHAEIVAIRAA ARALGNHRLTGCTLYVTLEPCAMCAGAIAHARIARLVYGAADPKGGAVDHGVRFFE SPTCHHRPEVTGGVLAAEAAALLRDFFRARR 459 DETYMRRALELARQAEEHGEVPVGAVLVKDGEIIAEGWNQSIGAHDATAHAEIMAL RAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGTVLN LFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKQAQREAEEK 460 MDEALAEARRAAAAGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAEIVALRAA ARALGNHRLTGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAVAHGPRFFG QPTCHHRPEVYGGIGEGAAAALLRAFFAARR 461 DESYMRRALELARQAEAEGEVPVGAVLVKDGEVVAEGWNRSIGAHDATAHAEIETL RKAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVLN LFESQASYHYAEVESGLLEDECREQLQAFFKRRRKEIKAQRQAQKEAEQK 462 MSEQDRYFMQRAIELAQQAELNGEVPVGAVLVKDGEVIAEGWNQSIGSHDATAHAE IMALRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEKKALKQAQKEAAQ 463 MTDADFMALALEEARAAAALGEVPVGAVVVKDGEVIARAGNRTVRDCDPTAHAEI VALREAARKLGNYRLDGCTLYVTLEPCAMCAGAMLHARLPRVVYGAADPKTGAAG SVLDLFAEPRLNHQTAVQGGVLADEAGALLRDFFKARRA 464 MDAALEEARRAAAAGEVPVGAVLVRDGVVLARAGNRTVRDCDPTAHAEIVALRAA AAALGNYRLDGCTLYVTLEPCAMCAGAMIHARLARLVYGAADPRTGAAGSVLDVL GHPALNHRTEVTGGVLAEECGALLREFFRTRRG 465 MSDKDLRFMQLALEEARAAADAGEVPVGAVLVRDGQVLARGRNRVILDNDPTAHA EIVALREGARRLGNYRLAGCTLYVTLEPCAMCAGAIVHARLDRLVYGAADPKAGAA GSVLDVLNHPKLNHQMEVEGGVLAAESGELLRSFFRARR 466 DTLYMRRALELAAQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATAHAEIETL RKAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVLN LFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAQKEAE 467 MDAALEEARRAAEAGEVPVGAVLVRDGAVLARAGNRTIRDCDPTAHAEIVALRAAA RALGNYRLPGTTLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVLDVIGH PALNHRMEVEGGVLAEECGALLREFFRARRG 468 DPLMDEFMGEALAEARAAAAAGEVPVGAVVVRDGAVIARAGNRTVRDCDPTAHAE IVALRAAARALGNHRLDGCDLYVTLEPCAMCAGAISHARIRRLYYGADDPKGGAVA HGARVFAHPTCHHRPEVYGGIGAAEAAGLLRAFFAARR 469 DESYMRRALELARQAEQEGEVPVGAVLVKDGEVIAEGWNRSIGAHDATAHAEIETL RKAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGTVL NLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKAQRDAEKAAK 470 MRDALAEARAAAARGEVPVGAVVVRDGAVLARAGNATIADCDPTAHAEMRALRA AARALGNYRLPGCTLYVTVEPCAMCAGAMIHARLARLVYGAADPKAGAAGSVLDV LGHPALNHRMEVTGGVLAAECAALLRDFFAARRGR 471 MTEEDKKFMQRAIELARKGEQEGEVPVGAVLVKDGEIIAEGWNRSIGDHDATAHAEI ETLRKAGKALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEKKALKQAKKEAEK 472 MDDDALMGLALDEARAAAAAGEVPIGAVVARDGAVVARAGNRTVRDCDPTAHAE VVALREAARALGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRVVYGAADPKTGAA GSVLDVLGHPALNHQTRVEGGVLAAECGALLRDFFAARR 473 MTRDEQYMRRALELARQAEQEGEVPVGAVLVKDGEIVAEGWNRSIGDHDATAHAEI ETLRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAEKEAEQK 474 DSEFMAEALAEARAAAAAGEVPVGAVVVKDGEIIARAGNRTLRDNDPTAHAEIVAL RAAARALGNQRLEGCDLYVTLEPCAMCAGAISHARIRRLYYGAEDPKGGAVDNGVR FFASPTCHHRPEVYGGIGETEAAELLRGFFRER 475 DDDERFMRLALEEARKAEEAGEVPVGAVLVKDGEVIARGRNRVISDSDPTAHAEIVA LREAGRALGNYRLDGCTLYVTLEPCAMCAGAMVHARLDRLVYGAADPRAGAAGSV LDVLNHPALNHRMEVEGGVLADECGALLRDFFRRRR 476 MDAALAEARAAADAGEVPVGAVVVRDGAVLARAGNRTLRDSDPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAISHARLARLHYGADDPKGGAVAHGPRFFA QPTCHHRPDVYGGIGEGEAAALLRGFFAARR 477 DTEFMREALAEARAAAAAGEVPVGAVVVKDGEIIARAGNRTLRDNDPTAHAEIVAL REAARKLGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGADDPKGGAVAHGPR FFAQPTCHHRPEVTGGVLAEEAGELLRGFFRERR 478 MDAALEEARRAAAAGEVPVGAVLVAGGRVLARAGNRTIRDCDPTAHAEIVALREAA RALGNYRLAGTTLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVFDVVR HPALNHRLEVEGGVLAEECGALLRDFFRARRGR 479 MRAALDEARRAAAAGEVPVGAVVVRDGVVLARAHNRTVADHDPTAHAEILALREA ARVLGNHRLTGCTLYVTLEPCAMCAGAIVHARLDRLVYGAADPKAGAAGSVLDVL DHPRLNHRMEVTGGVLAEESAALLRGFFAARR 480 MSSDADFMRLALAEARAAAAAGEVPVGAVVVRGGEVIARAGNRTVRDCDPTAHAE VVALREAARKLGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAV AHGPRFFAQPTCHHRPEVTGGVLAEEAGELLRGFFRARR 481 MDAALEEARRAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVFDVL GSARLNHRVEVEGGVRAAECGALLRDFFAARRGR 482 MRAALAEARRAAAEGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAEVLALREA ARALGNHRLTGCTLYVTVEPCAMCAGAISHARVARLVYGADDPKGGAVRHGPRVF DQPTCHHRPEVVGGVLAEEAGALLRDFFAARR 483 DTSFMQQALDEARAAAAAGEVPVGAVVVKDGEIIARAGNRTLRDNDPTAHAEIVAL RAAARALGSQRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAVAHGA RVFSHPQCHHVPEVYDGIGAGEAAALLRDFFAGR 484 DTEFMREALAEARAAAAAGEVPVGAVVVRDGAIIARAGNRTIRDRDPTAHAEVVAL REAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGAADPKGGAVAHGP RFFEQPTCHHRPEVTGGVLAEEAGALLRDFFRARR 485 MSEQDEFYMRRAIELARKGEENGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAHAEI VTLRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEKKALKQAQKELE 486 MTDADFMALALAEARAAAAAGEVPVGAVVVRDGVVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNYRLDGCTLYVTLEPCAMCAGAMLHARLARVVYGAADPKTGA AGSVLDLFAQPRLNHHTAVAGGVLAAECGALLADFFRQRRG 487 MSDEQYMRRALELARQAEQQGEVPVGAVLVRDGEVIAEGWNQSISSHDATAHAEM MAIRAAGAALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAEKEAAAK 488 MSSETSTDAAADAAFMAEALAEARAAAAAGEVPVGAVVVCGGRIVARAGNRTVRD NDPTAHAEIVALREAARVLGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGADD PKGGAVRHGPRFFAQPTCHHRPDVAGGVGEAEAAELLRAFFRARR 489 MTDADFMALALEEARAAAALGEVPVGAVVVKDGEVIARAGNRTIRDCDPTAHAEIV ALREAARKLGNYRLDGCDLYVTLEPCAMCAGAMIHARLARLVYGAADPKTGAAGS VLDVFANPQLNHHTAVVGGVLADEAGALLREFFAARR 490 MDDDARFMGEALAEARAAAAAGEVPIGAVVVRDGAVVARAGNRTVRDNDPTAHA EVLALREAARALGSQRLTGCTLYVTLEPCAMCAGAISHARVARLVYGAADPKGGAV AHGPRFFAQPTCHHRPEVTGGVGEAEAAALLRDFFRARR 491 DRLFMEEALAEARAAAAAGEVPIGAVVVRDGEIVARAGNRTVRDCDPTAHAEIVAL REAARALGNYRLTGCTLYVTIEPCAMCAGAMIHARLDRLVYGADDPKAGAVRSVLQ VLDHPALNHRVEVESGVLAAECAALLQEFFASRR 492 DSLTRDELYMRRALELAALAEAEGEVPVGAVLVKDGEIVGEGWNRSIGSHDATAHA EIMALRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGASDLKAGAA GTVLNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEIKAQRQAEKAAQ 493 MRAALAEARRAAEAGEVPVGAVVVRDGAVLAAAGNRTVRDCDPTAHAEIVALRAA ARAAGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVTGGVLAEEAGALLRDFFRARR 494 MSAALEEARRAAAAGEVPVGAVLVRDGAVLARGGNRTIRDCDPTAHAEIVALRAAA RALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVEDVLR HPALNHRMEVEGGVLAEECGALLRDFFRARR 495 DDTEFMRLALAEAEAAAAAGEVPVGAVVVRDGEVIARAGNRTIRDCDPTAHAEVVA LREAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRVVYGAADPKTGAAGSV LDLFATRQLNHHTQVTGGVLAEECGALLRGFFEARR 496 DTLYMRRALELAAQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGDHDATAHAEIQTL RKAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVLN LFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKALRQAEKAAEQ 497 DDPYMALALEEARAAAAAGEVPIGAVVVRDGEVVARAGNRTVRDNDPTAHAEVVA LREAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVRHG ARVFEHPQCHHRPEVTGGVGAAEAGELLRGFFRARR 498 MDSKEKDEFFMRRALELARLGEEKGEVPVGAVLVKDGEIIAEGWNQSIGENDATAH AEIMALRKAGKALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGA AGTVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKEKKKAEKAALEA 499 MRSALDLAAAAAAAGEVPVGAVVVRDGAIVGRGENRVLRDSDPTAHAEIVALREAA RALGNYRLTGCTLYVTLEPCAMCAGAMIHARIDRLVYGAADPKAGAAGSVLDVLG HPALNHQMEVEGGVLAEECGALLRDFFRARR 500 MDAALAEARAAADAGEVPVGAVVVRDGVVLARAGNRTVRDADPTAHAEIVALRA AARALGNHRLGGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVRHGPRL FASPTCHHRPEVVSGVGEAEAAALLRDFFAARR 501 MDAALEEARRAAAAGEVPVGAVLVRDGVVLARAGNRTIRDCDPTAHAEIVALREAA RAAGNYRLPGTTLYVTLEPCAMCAGAMIHARVDRLVYGAADPRAGAAGSVFDVVR HPALNHRMEVEGGVLADESAALLRGFFRARR 502 MTSEDEKYMRRALELARQAEQEGEVPVGAVLVKDGEIVAEGWNRSIGDHDATAHA EIETLRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAA GTVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQKEAEQK 503 DEPYMRLALDEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDNDPTAHAEVLA LREAARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHG PRFFAQPTCHHRPEVTGGVLAEEAGALLRDFFRARR 504 MDAALAEARAAADAGEVPVGAVVVRDGAVLARAGNRTLRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAISHARLARLVYGADDPKGGAVAHGPRFFG QPTCHHRPEVVGGVGAAAAGDLLRGFFRARR 505 RSSPEEAAMDDAGFMRLALAEAEAAAAAGEVPVGAVVVLGGEVIARAGNRTVRDN DPTAHAEIVALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLARLVYGAAD PKTGAAGSVLDLVAHPALNHRMEVEGGVLAAECGALLRDFFAARRG 506 MTRDEQYMRRALELARQAEAEGEVPVGAVLVRDGEVIAEGWNRSIGAHDATAHAEI MALRQAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVYGAPDLKAGAAG TVLNLFESQASYHYAEVEGGLLEEECREQLQAFFKRRRKEIKAARQARRAAEE 507 MRAALAEARAAAEAGEVPVGAVVVHEGRIIARAQNRVERDHDPTAHAEILALRAAA AALGATRLGGCTLYVTLEPCAMCAGAIAHARVARLVYGADDPKGGAVAHGPRFFT QPTCHHRPEVTGGVGEAEAAALLRDFFRARR 508 MDDAGFMREALAEAEAAAAAGEVPVGAVVVKDGEIIARARNATVARNDPTAHAEIL ALREAARVLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGAADPKAGACGSV LDVIGHPRLNHRVEVAGGVLAEECGALLREFFRSRR 509 DETYMRRALELARQAEQAGEVPVGAVLVKDGEIVAEGWNQSIGTHDATAHAEIMAL RAAGQALENYRLVDTTLYVTLEPCPMCAGALLHSRVKRVVFGAADLKAGAAGTVL NLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALKQAEKAAQE 510 MNSDDLYMRRALELARQAEEEGEVPVGAVLVKDGEIVAEGWNRSIGSHDATAHAEI ETLRKAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKALRQAQKEAEE 511 MDAALAEARAAADAGEVPVGAVLVRDGVVLARAGNRTVRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVDRLVFGARDPRAGAAGSVFDVLR HPALNHRVEVVEGVRAEECGALLRDFFRARR 512 DRLFMRRALELAAQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATAHAEIETLR KAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVLNL FESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKAARQAKREQE 513 MDDARFMAEALAEARAAAAAGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAE IVALREAARALGNYRLDGCTLYVTLEPCAMCAGAMLHARLPRLVYGAADPKTGAA GSVLDLFAERRLNHQTEVRGGVLAEACGALLTDFFRSRRA 514 DSEFMAEALAEARAAAEAGEVPIGAVVVCDGEIVARAGNRTIRDNDPTAHAEIVALR EAARKLGNYRLTGCTVYVTLEPCAMCAGAMIHARLDRLVYGAADPKAGAAGSVLD VLGHPRLNHQMAVESGVLADECGALLRDFFRSRR 515 MDSESDLRFMREALAEARAAAAAGEVPVGAVVVRDGAILARAGNRTLRDNDPTAH AEIVALRAAAAALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGA VAHGPRFFEQPTCHHRPEVAGGVLAEEAGALLRAFFAARR 516 MSSDAGFMAEALAEARAAAAAGEVPVGAVVVRDGAIVARAGNRTVRDNDPTAHAE VVALREAARALGNHRLGGCELYVTLEPCAMCAGAISHARIARLYYGADDPKGGAVA HGARVFSHPQCHHRPEVYDGIGAGEAAALLRDFFAARR 517 DRDDRYMRLALEEARAAAEAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEIV ALREAARVLGNYRLAGCTLYVTVEPCAMCAGAMIHARVDRLVYGADDPKGGAVRS CLQVLDHPRLNHRVEVTAGVLAEECAALLQSFFAARR 518 DSEFMAEALAEARAAAAAGEVPVGAVVVRDGEIVARAGNRTLRDNDPTAHAEIVAL REAARALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGADDPKGGGVAHGAR VFEHPQCHHRPEVVGGVGAAEAGELLRGFFAARR 519 DREEYLMRKALELAAKAEQLGEVPVGAVLVKDGEIIAEGWNQSIGNHDATAHAEIM TLRQAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKALKQAKRDAEEN 520 MDAALAEARAAADAGEVPVGAVVVRDGAVLARAGNRTLRDADPTAHAEIVALRAA ARALGNHRLGGCTLYVTLEPCAMCAGAISHARLARLHYGAADPKGGAVEHGPRFFA QPTCHHRPDVYGGIGEGEAAALLRGFFAARR 521 DEPYMRLALDEARAAAAAGEVPIGAVVVKDGEVIARARNRTLADNDPTAHAEIVAL RAAAAALGNHRLTGCELYVTLEPCAMCAGAISHARIARLVYGADDPKGGAVAHGPR FFAQPTCHHRPEVVGGVGEGEAAELLRGFFAARR 522 DRDSRFMREALAEARAAAEAGEVPIGAVVVRDGEIVARAGNRTVRDCDPTAHAEIV ALREAARALGNYRLTGCTLYVTIEPCAMCAGAMIHARIDRLVYGAADPKAGAAGSV LDVLGHPRLNHRMEVTAGVLAEECAALLRDFFAARR 523 MDAALEEARRAAAAGEVPVGAVLVHDGQILARAGNRTIRDNDPTAHAEIVVLREAA RALGNYRLEGCTLYVTLEPCAMCAGAMIHARLPRLVYGADDPKAGAAGSVLDVLN HPALNHRMEVEGGVLAAECGALLRDFFRARR 524 MSAADDIRFMREALAEARAAAAAGEVPVGAVVVRDGAILARAGNRTIRDCDPTAHA EVVALREAARALGNHRLTGCTLYVTLEPCAMCAGAISQARVARLVYGADDPKGGA VAHGPRFFAQPTCHHRPEVTGGVLAEEAGALLRDFFRARR 525 MTDADFMALALEEARAAAALGEVPVGAVVVKDGEVIARAGNRTIRDCDPTAHAEV VALREAARKLGNYRLPGLTLYVTLEPCAMCAGAMIHARLDRVVYGADDPKGGAAR SVYRILDDPRLNHQVAVTSGVLAEECGALLRDFFRARR 526 MDSAAKDLCYMRRALELAALAEAEGEVPVGAVLVRDGEIVGEGWNRSIGSHDATA HAEIMALRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAG AAGTVLNLFESQASYHYADVEGGLLAEECRAQLQAFFKRRRKEQKALRQAQKEAA 527 DEEFMREALAEAQAAADAGEVPIGAVVVCDGEIVARAGNRTIRDNDPTAHAEIVALR EAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARVDRLVYGADDPKAGAAGSVLD VIGHPRLNHRMEVTSGVLAEECGAMLREFFRRRRA 528 MDDAGFMRLALAEARAAAAAGEVPVGAVVVRGGEVLAAAGNRTLRDCDPTAHAE VVALRAAARALGNHRLDGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAV AHGPRFFAQPTCHHRPEVYGGIGESEAAALLRDFFAARR 529 MSDEDYMRLALAEAQAAADAGEVPVGAVLVAGGEVVARGRNRMIADSDPTAHAEI VALREAARRLGNYRLTGCTLYVTLEPCAMCAGAIVHARLDRVVYGAADPKAGAAG SVLDVLGHPRLNHRTEVTGGVLADECGALLKDFFRARR 530 MSSEDEKYMRRALELARQAEEEGEVPVGAVLVKDGEIVAEGWNRSIGSHDATAHAE IETLRKAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKAARKAAKAE 531 MSDDAAFMGEALAEARAAAAAGEVPIGAVVVCDGAIVARAGNRTVRDNDPTAHAE IVALREAAARLGNYRLTGCTLYVTLEPCAMCAGAMIHARIDRLVYGAADPKAGAAG SVLDVIGHPRLNHRMEVEGGVLAAECGALLRDFFASRR 532 MRAALAEAERAAAAGEVPVGAVVVRDGAVLAAAGNRTVRDCDPTAHAEVLALRA AARALGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHGPRFF AQPTCHHRPEVAGGLGAAAAGELLRAFFRARR 533 MRAALDEARAAAAAGEVPVGAVVVHEGRIVARAQNRMRRDNDPTAHAEIVALRAA AAALGSMRLTGCTLYVTLEPCAMCAGAISHARIDRLVYGAADPKGGAVAHGPRFFE QPTCHHRPDVVGGVLAEEAGALLRGFFAARR 534 MDSAAKDLCYMRRALELAALAEAEGEVPVGAVLVKDGEIVGEGWNRSIGSHDATA HAEIMALRQAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAG AAGTVLNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEIKAQRDAQRAADE 535 MNDEFYMRRALELAALAEEHNEVPVGAVLVLNGEIIGEGWNRSIGQHDATAHAEIM ALRQAGKVLQNYRLLDTTLYVTLEPCPMCAGALVHSRVKRVVYGTPDLKAGAAGT VMNLLSYDAVNHHVAITSGVLAEECREQLQAFFRRRRAEKKALKQAQRA 536 DDTFYMRRALELARQAEAEGEVPVGAVLVRDGEVIAEGWNRSIGDHDATAHAEIQV LRKAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVYGAPDLKAGAAGTV LNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAARQAKRAAE 537 MRSALDLAAAAAAAGEVPVGAVVVRDGAIVGRGENRVLRDSDPTAHAEIVAMREA ARALGNYRLTGCTLYVTLEPCAMCAGAMIHARIDRLVYGAADPKAGAAGSVLDVL NHPRLNHQMEVEGGVLAAECGAMLRDFFRARR 538 MDDDALMGLALDEARAAAAAGEVPIGAVVARDGEVVARAGNRTVRDCDPTAHAEI VALREAARKLGNYRLTGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPKTGAAG SVLDVLGHPALNHQTQVEGGVLAEECGALLRDFFRERR 539 MTEEDKYFMRRAIELAKLAEENGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAHAE MMAIREAGKVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKAQKEAEE 540 DDDYMRLALAEARAAAEAGEVPIGAVVVCGGEVVARAGNRTVADCDPTAHAEIVA LREAARKLGNYRLTGCTLYVTLEPCAMCAGAMIHARLDRLVYGADDPKAGAAGSV LDVLGHPALNHQMQVTAGVLADECAALLRDFFRARR 541 DDSFYMRRALELAALAEREGEVPVGAVLVKDGEIIAEGWNRSIGSHDATAHAEIETL RKAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGTVLN LFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAQRDAEKAAAEK 542 MDAALAEARAAADAGEVPVGAVVVRDGAVLARAGNRTLRDSDPTAHAEIVALRAA ARALGNHRLGGCDLYVTLEPCAMCAGAISHARIARLYYGADDPKGGAVAHGARVF AHPQCHHRPEVYDGIGAAEAAALLRDFFAARR 543 MTRDEQYMRRALELARQAEAEGEVPVGAVLVKDGEIIAEGWNRSIGSHDATGHAEI MALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAEKAAAE 544 MTDADFMALALEEARAAAALGEVPVGAVVVKDGEVIARAGNRTIRDCDPTAHAEIV ALREAARKLGNYRLPGLALYVTLEPCAMCAGAMIHARLARLVYGAADPKTGAAGS VLDVLGHPALNHQTAVTGGVLAEEAGALLRDFFAARRAAG 545 MDAALAEARAAADAGEVPVGAVVVRDGAVLARAGNRTLRDADPTAHAEIVALRAA ARALGNHRLPGCTLYVTLEPCAMCAGAISHARIARLVYGAADPKGGAVAHGPRFFE QPTCHHRPEVVGGLGETEAAALLRAFFAARR 546 MDAALEEARRAAAAGEVPVGAVLVAGGRVLARAGNRTIRDCDPTAHAEIVALRAA ARALGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPKTGAAGSVEDVL GSGRLNHRVAVEGGVRAEECGALLRDFFRARR 547 DDDERWMREALAEARAAAEAGEVPVGAVVVRDGELIARGRNRVEADADPSAHAEI VALREAARRLGNHRLTGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVR HGARVFEQPTCHHRPEVVGGVLASESAALLRDFFRARR 548 MSAADEQFMRRAIELARQAEAEGEVPVGAVLVKDGEIVAEGWNRSIGAHDATAHAE IETLRKAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAQKAAEE 549 MSSAPSDADFMGLALEQARLAAAAGEVPVGAVVVRDGEVIAQAHNRTVADCDPTA HAEVVALRAAARALGNHRLTGCTLYVTLEPCAMCAGAIAHARVARVVYGAADPKG GAVEHGPRFFAQPTCHHRPEVVGGVGAAEAGALLRDFFRARR 550 MDEALAEARRAAAAGEVPVGAVVVRDGVVLARAGNRTVRDADPTAHAEIVALRAA AAALGNYRLDGCTLYVTLEPCAMCAGAMVHARLARLVYGAADPRAGAAGSVLDV LGHPALNHRMEVAGGVRAEECAALLRDFFAARRG 551 MDEALAEARRAAEAGEVPVGAVVVRDGAVLARAGNRTVRDCDPTAHAEVLALREA ARALGNHRLAGCTLYVTLEPCAMCAGAISHARVARLVYGADDPKGGAVAHGPRFF GQPTCHHRPEVAAGLGAAEAGALLRDFFAARR 552 DTSFMRLALDEARAAADAGEVPVGAVVVCDGEVIARAGNRTVRDCDPTAHAEIVAL REAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGAADPKAGAAGSVL DVLGHPALNHQTQVEGGVLAAECGALLRDFFRARR 553 DTLFMRRALELAAQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATAHAEIETLR KAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVLNL FESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAEKEAEK 554 MDDEFFMRQALREARKAYDEGEVPVGAVVVRDGKVIARGRNQVERLKDPTAHAEM IALTAAAAHLGSKWLKGCTLYVTVEPCAMCAGALVLARLERLVFGARDPKAGACGS VLDIVRHPRLNHRVEVVSGVLEEECGALLKEFFRRLR 555 MTRDEQYMRRALALARQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGRHDATAHAEI ETLRKAGQVLGNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKAARKAAKEAE 556 MDAALEEARRAAAAGEVPVGAVLVRDGEVLARAGNRTVRDNDPTAHAEILVIREAA RRLGNYRLEGCVLYVTLEPCAMCAGAMVHARLPRLVYGAADPKAGAAGSVLDVLG HPALNHRVEVTGGVLADACGALLRDFFAARR 557 MDEALAEARRAAAAGEVPVGAVLVRDGEVLARGGNRTIRDCDPTAHAEIVALREAA RRAGNYRLPGTTLYVTLEPCAMCAGAMIHARVARLVYGAADPRAGAAGSVEDVLR HPALNHRMEVEGGVRAEECGALLREFFRARR 558 MTEKDEFYMKRAIELARKGEEEGEVPVGAVLVKDGEIIAEGWNRSIGSHDATAHAEI ETLRKAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKAKKEEQDK 559 DDDFMALALEEARAAAEAGEVPIGAVVVCDGEVVARAGNRTVRDNDPTAHAEIVAL REAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRVVYGADDPKAGAARSVL NVLDHPALNHRVAVEGGVLADECGALLREFFRARR 560 MTEEDKYFMQRAIELARQAELAGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAHAEI MALRQAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEIKALKQAQKEAEN 561 MTDEEYMRRALELARQAEQQGEVPVGAVLVKDGEVIAEGWNQSIGSHDATAHAEI MALRAAGQALENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKAARQAKREAE 562 MSEQDEFYMRRAIELARQAEAEGEVPVGAVLVKDGEIVAEGWNRSIGSHDATAHAEI ETLRKAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGAPDLKAGAAGT VLNLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAQKEAEEK 563 DDTLYMKRALELARQAEAEGEVPVGAVLVKDGEVIAEGWNRSIGSHDATAHAEIET LRKAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGTVL NLFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAEKEAE 564 DETYMRRALELARQAEEHGEVPVGAVLVKDGEIIAEGWNRSIGDHDATAHAEIMAL REAGKTLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVYGAPDLKAGAAGTVLN LFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKAARKARREAEEK 565 MTDADFMALALEEARAAAALGEVPVGAVVVRDGAVIARAGNRTIRDCDPTAHAEIV ALRAAARALGNYRLDGCDLYVTLEPCAMCAGAMIHARLARLVYGAADPKTGAAGS VLDVFANPRLNHHTAVVGGVLADEAAALLRGFFAARR 566 DDEKWMRYALSLADKAEALGEVPVGAVLVKDNQVIGEGWNQSISGHDATAHAEIM AIRDAGKNLQNYRLIDCTLYVTLEPCPMCAGAIVHSRIKRVVFGASDYKTGAAGSVF NLLSNEQLNHQAEVTAGVLAEECGEKISAFFKRRRKEKKAAKKAAKLAE 567 MTEEDKYFMRRAIELAKLAEENGEVPVGAVLVKDGEIIAEGWNQSIGSHDATAHAE MMAIRQAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAG TVLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALKKAQKEAE 568 MTDDERWMREALAEARAAEAAGEVPVGAVVVRDGELIARGRNRVLRDSDPTAHAE IVALREAARALGNYRLDGCTLYATLEPCAMCAGAMLHARLARLVYGAADPKAGAA GSVLDVLGHPRLNHRMEVTGGVLAEEAGALLREFFRARR 569 DDSFYMRRALELAALAEAEGEVPVGAVLVKDGEIIAEGWNRSIGDHDATAHAEIQVL RKAGQALQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVYGAPDLKAGAAGTVLN LFESQASYHYAEVESGLLEEECREQLQAFFKRRRKEIKALRQAEKEAQN 570 DEEFMREALAEAQAAADAGEVPIGAVVVCDGEIVARAGNRTIRDNDPTAHAEIVALR EAARKLGNYRLAGCTLYVTLEPCAMCAGAMIHARIDRLVYGADDPKAGAAGSVLD VLGHPRLNHQMQVERGVLAAECGAMLTRFFQARR 571 MTEADEKFMRRAIELAREAEEHGEVPVGAVLVKDGEIIAEGWNRSIGEHDATAHAEI ETLRKAGQVLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEEECREQLQAFFKRRRKEIKALRQAEKAAG 572 MRDALALAAAAAAAGEVPVGAVVVHGGEIVGRGENRVLRDSDPTAHAEIVALREA ARALGNYRLTGCDLYVTLEPCAMCAGAMIHARIARLVYGAADPKAGAAGSVLDVL NHPRLNHRMEVTGGVLAEECGALLRDFFRARR 573 MTEEDKYFMQRAIELARLAEENGEVPVGAVLVKDGEIIAEGWNQSIGNHDATAHAEI MTLRQAGQVLQNYRLLDTTLYVTLEPCPMCAGALLHSRVKRIVFGAPDLKAGAAGT VLNLFESQASYHYADVESGLLEDECREQLQAFFKRRRKEIKALKKAKRDAEN 574 MDPTDLAFMREALAEARAAAEAGEFPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 575 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNIRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 576 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKTGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 577 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGCGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 578 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAGHLGSGRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 579 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 580 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANAGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 581 MDDAGFMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKTGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 582 MDDAGFMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGAGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 583 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAGHLGSSRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 584 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 585 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 586 MDPTDLAFMREALAEARAAAEAGELPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGTGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 587 MDPTDLAFMREALAEARAAAEAGEMPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 588 MDDAGFMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 589 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGRGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 590 MDDAGFMRLALEEARAAAAAGEVPIGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGSGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 591 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVIRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 592 MDPTDLAFMREALAEARAAAEAGEIPVGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 593 MDPTDLAFMREALAEARAAAEAGELPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 594 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNVRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 595 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNSRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 596 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKRGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 597 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGSGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 598 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNFRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGRGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 599 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANDGAGACG SVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 600 MDPTDLAFMREALAEARAAAEAGEFPVGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGTGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 601 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNWRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 602 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANAGSGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 603 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAGHLGSGRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLSHRPEVVGGVLEAECAALMRDFFRER 604 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSRRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 605 MDPTDLAFMREALAEARAAAEAGEIPIGAVVVCDGRIVARAHNRPIALSDPTAHAEIL ALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGSV LDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 606 MDPTDLAFMREALAEARAAAEAGEFPVGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 607 MDPTDLAFMREALAEARAAAEAGEIPVGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANAGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 608 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGTGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 609 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEM LALTAAAGHLGSRSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 610 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVVRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 611 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANDGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 612 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANSGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 613 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNTRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 614 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVNRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 615 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVNRLKDPTAHAEM LALTAAAGHLGSRSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 616 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANAGTGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 617 MDPTDLAFMREALAEARAAAEAGEFPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGTGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 618 MDPTDLAFMREALAEARAAAEAGEVPIGAVVVCDGRIVARAHNRPIALSDPTAHAEI LALREAARALGNIRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGTGACGSV LDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 619 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPGAGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 620 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANAGRGAAG SVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 621 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE VLALREAAAALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 622 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE VLALREAAAALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 623 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAGKALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 624 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE VLALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 625 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDRDPTAHAEI VAIREAARRLGSYRLAGCTLYVTLEPCPMCAGAMIHARLDRLVYGVANPKAGAAGT VLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 626 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSRSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 627 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSARLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 628 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAARALGDYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACG SVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 629 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAAAALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 630 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAGRALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 631 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALADPTAHAE VLALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 632 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAGRALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 633 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE ILALREAGRALGNYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 634 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAAAALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACG TVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 635 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAGRALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 636 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALADPTAHAE VLALREAARALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACG SVLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 637 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDRDPTAHAE VVALREAARRLGSYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAA GTVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 638 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDRDPTAHAEI VAIREAARRLGSYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAGT VLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 639 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDKDPTAHAEI VALREAARRLGSYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAG TVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 640 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVVRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLSHRPEVVGGVLEAECAALMRDFFRER 641 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 642 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 643 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAAAALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACG TVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 644 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVVRLKDPTAHAEM LALTAAAGHLGSSRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 645 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSPSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRTGACGS VFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 646 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 647 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAGRALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 648 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAAKALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 649 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAAAALGDYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 650 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE ILALREAGRALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 651 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDRDPTAHAEI VALREAARRLGSYRLAGCTLYVTLEPCPMCAGAMIHARLDRLVYGVANPKAGAAG TVLDILGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 652 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDRDPTAHAE VVAIREAARRLGSYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAA GTVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 653 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVNRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRTGACG SVFDIPGDRRLSHRPEVVGGVLEAECAALMRDFFRER 654 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSPQLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 655 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAGRALGNYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 656 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 657 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAARALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACG TVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 658 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 659 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALADPTAHAE ILALREAAKALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 660 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSPRLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACG SVFDIPGDRRLSHRPEVVGGVLEAECAALMRDFFRER 661 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSARLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRTGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 662 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVIRLKDPTAHAEM LALTAAAGHLGSPSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRTGACGS VFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 663 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 664 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 665 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAAKALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACG TVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 666 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE VLALREAGRALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 667 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDKDPTAHAEI VAIREAARRLGSYRLAGCTLYVTLEPCPMCAGAMIHARLDRLVYGVANPKAGAAGT VLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 668 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVRRLKDPTAHAEM LALTAAAGHLGSPSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKTGACGS VFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 669 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVIRLKDPTAHAEM LALTAAAGHLGSRSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRAGACG SVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 670 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVVRLKDPTAHAEM LALTAAAGHLGSPSLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPRTGACGS VFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 671 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAAAALGNYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGS VLDVMNHPLLNHRVEVTGGVLAEECGALLSGFFRAR 672 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALRDPTAHAE ILALREAAAALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 673 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPKLNHRVEVTGGVLAEECGALLSGFFRAR 674 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAARALGSYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 675 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALKDPTAHAE ILALREAAAALGDYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGACGT VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR 676 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEIL ALRAACRHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 677 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEIL ALSAACRHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 678 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDATAHAEI LALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 679 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALRAACEHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 680 MDPEDLAFMRKALEEARQARDAGEVPVGAVVVLDGEIVARAHNRTIQLSDPTAHAE ILALREAARALGNYRLEGCTLYVTLEPCAMCAGAILHARIERLVFGVANPKAGAAGS VLDVLNHPRLNHRVEVTGGVLAEECGALLRDFFRAR 681 MDPTDEAFMKKALDEAKKAAEAGEVPVGAVVVYDGKVVARAHNRRIAESDPTAHA EILALREAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIARLVYGVPNPKAGATG SVLNVLNHPRLNHRVEVTGGVLAEECGDLLRGFFRAR 682 MDDEGWMQLALEEARASRAAGEVPVGAVVVRDGEVLARAGNRTRELCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRLEVTGGVLAAECGQLLRDFFRAR 683 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEIL ALKAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 684 MDPTDVAFMQQALDEARAAREAGEVPVGAVVVYDGRVVARAHNRTIARSDPTAHA EILALREAARALGNYRLAGCTLYVTLEPCAMCAGAILHARIERLVYGVPNPKAGATG SVLNVLNHPRLNHRVEVTGGVLAEECGALLRGFFRAR 685 MDPEDLRFMRKALAEARKAKEAGEVPVGAVVVKDGKIVAQAHNRTIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVPNPKAGASGS VLNVLNHPRLNHQVEVTGGVLAEECGALLRDFFRAR 686 MDPKDLRFMQKALAEAREAKAAGEVPVGAVVVRNGKIVARAHNRTRALSDPTAHA EILALREAARALGNYRLEGCTLYVTLEPCAMCAGAILHARIERLVYGVANPKAGAAG SVLDVLNHPRLNHRVEVTGGVLAEECGALLRGFFRAR 687 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEIL ALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 688 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLQDPTAHAEIL ALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 689 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDPTAHAEV LALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRMNHRPEVVGGVLEAECAALMRDFFRER 690 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDATAHAEI LALRAACRHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 691 MDALDIEFMRKALAEARAAKEAGEVPVGAVVVRDGKIVARAHNRTIALSDPTAHAE ILALRAAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIERLVYGVPNPKAGATGS VLNVLNHPRLNHRVEVTGGVLAEECGRLLSDFFRAR 692 MDPDDIAFMREALAEARRAKEAGEVPVGAVVVKDGRIVARAHNRTIAESDPTAHAEI LALREAARQLGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVPNPKAGATGS VLDVMNHPRLNHRVEVTGGVLADECGDLLRDFFRAR 693 MDPEDIAFMEQALAEARAARDAGEVPVGAVVVLDGEIVAQAHNRTRQLSDPTAHAE ILALRQAARALGNYRLTGCTLYVTLEPCAMCAGAILHARVERLVYGVANPKAGATG SVLNVLNHPRLNHRVEVTGGVLAEECGDLLRGFFRAR 694 MDDQDLRFMKMALDEARKAKDAGEVPVGAVVVHEGEVVARAHNRTIARSDPTAH AEIRALREAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIARLVYGVPNPKAGAT GSVLNVLNHPRLNHRVEVTGGVLAEECGDLLRDFFRAR 695 MDDEGWMRLALEEARASRAAGEVPVGAVVVRDGQVLARAGNRTRERCDPTAHAEI VALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAA GSVLDVLGHPRLNHRLEVTGGVLEAECGQLLRDFFRAR 696 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDPTAHAEL LALRAACEHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 697 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALRAAARHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 698 MDAEDLAFMRQALAEAREAKEAGEVPVGAVVVHDGRVVARAHNRTIRLSDPTAHA EILALREAARALGNYRLAGCTLYVTLEPCAMCAGAILHARIQRLVYGVPNPKAGAAG SVLDVLNHPRLNHRVEVTGGVLAEECAALLTDFFRAR 699 MDPEDVEFMRKALAEAREARQAGEVPVGAVVVHDGKIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLEGCTLYVTLEPCAMCAGAILHARIQRLVYGVPNPKAGATGS VLNVMNHPRLNHRVEVTGGVLAEECGALLSDFFRAR 700 MDPEDLRFMREALDEAREAREAGEVPVGAVVVRDGRIVARAHNRTKELSDPTAHAE ILALRAAARALGNYRLAGCTLYCTLEPCAMCAGAILHARIARLVYGVPNPKAGAAGS VLDVLNHPRLNHRVEVTGGVLAEECGALLRGFFRAR 701 MDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDADPTAHAE VVAIREAARRLGSYRLAGCTLYVTLEPCPMCAGAMIHARLDRLVYGVANPKAGAAG TVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAR 702 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDPTAHAEIL ALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 703 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDPTAHAEL LALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 704 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALRAAAAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 705 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDATAHAEI LALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 706 MDPKDIRFMRKALAEAREARDAGEVPVGAVVVHDGEIVAQAHNRPIAESDPTAHAEI LALREAARALGNYRLEGCTLYVTLEPCAMCAGAILHARIARLVYGVANPKAGAAGS VLNVLNHPRLNHRVEVTGGVLADECGDLLRDFFRAR 707 MDSEDIKFMRQALAEAREAREAGEVPVGAVVVHDGRIVARAHNRRILESDPTAHAEI LALRQAARALGNYRLTGCTLYATLEPCAMCAGAILHARIERLVYGVANPKAGATGS VLNVLNHPRLNHRVEVTGGVLEEECGALLRDFFRAR 708 MDPVDVRFMKKALAEAREAKEAGEVPVGAVVVKDGEVVARAHNRTIARSDPTAHA EINALRAAARALGNYRLEGCTLYVTLEPCAMCAGAILHARIQRLVYGVPNPKAGAA GSVLDVLNHPRLNHRVEVTGGVLAEECGALLSDFFRAR 709 MDPDDIKFMRQALAEARKAREAGEVPVGAVVVKDGRVVARAHNRTIALSDPTAHA EIRALREAARALGNYRLVGCTLYVTLEPCAMCAGAILHARIARLVYGVPNPKAGAAG SVLDVMNHPRLNHRVEVTGGVLAEECGALMSDFFRAR 710 MDDEGWMQLALEEARASRAAGEVPVGAVVVRDGEVLARAGNRTRERCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVTGGVLADECGRLLRDFFRAR 711 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALKAAAAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 712 MDPEDIEFMEQALAEAKAAREAGEVPVGAVVVHDGKIVARAHNRTRALSDPTAHAE ILALREAARALGNYRLEGCTLYATLEPCAMCAGAILHARIERLVYGVANPKAGATGS VLDVLNHPRLNHRVEVTGGVLAEECGALLSDFFRAR 713 MDPEDIAFMRMALAEARKAKEAGEVPVGAVVVLNGEIVARAHNRPIALSDPTAHAEI LALREAARALGNYRLPGCTLYVTLEPCAMCAGAILHARIERLVYGVANPKAGATGS VLDVLNHPRLNHKVEVTGGVLAEECGALLRGFFRAR 714 MDAEDLEFMQQALDEAREAREAGEVPVGAVVVLDGRIVARAHNRPIAESDPTAHAE ILALRAAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIERLVYGVPNPKAGACGS VLNVMNHPRLNHRVEVVGGVLAEECGALLTGFFRAR 715 MDPKDIKFMEKALEEARKAKEAGEVPVGAVVVKDGRIVARAHNRTIELSDPTAHAEI RALREAARALGNYRLEGCTLYATLEPCAMCAGAILHARIERLVYGVPNPKAGATGSV LDVLNHPRLNHRVEVTGGVLAEECGALLRGFFRAR 716 MDDEGWMRLALEEARASRAAGEVPVGAVVVRDGEVLARAGNRTRELCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVTGGVLAEECGALMRDFFRAR 717 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTAHAEIL ALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGNRKLNHRPEVVGGVLEAECAALMRDFFRER 718 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALRAACRHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGNRRLNHRPEVVGGVLEAECAALMRDFFRER 719 MDPEDIAFMRKALAEARKAKEAGEVPVGAVVVKDGKIVARAHNRTIALSDPTAHAE ILALREAARALGNYRLTGCTLYVTLEPCAMCAGAILHARIEKLVYGVPNPKAGACGS VLNVLNHPRLNHRVEVTGGVLAEECGALLKDFFRAR 720 MDPEDVRYMRKALAEARKAKEAGEVPVGAVVVHDGRVVARAHNRTIALSDPTAHA EILALREAARALGNYRLEGCTLYATLEPCAMCAGAILHARIQRLVYGVANPKAGAAG SVLDVMNHPRLNHRVEVTGGVLEEECGALLSDFFRAR 721 MDPEDVAFMKKALAEARAAQEAGEVPVGAVVVKDGEVVARAHNRTRERSDPTAH AEILALREAARALGNYRLAGCTLYVTLEPCAMCAGAILHARIERLVYGVANPKAGAA GSVLNVLNHPRLNHRVEVTGGVLAEECGDLLRGFFRAR 722 MDPTDLEFMRQALAEAREARDAGEVPVGAVVVHDGRIVARAHNRTRELSDPTAHAE ILALRAAARALGNYRLTGCTLYATLEPCAMCAGAILHARIERLVYGVANPKAGACGS VLHVLNHPRLNHRVEVTGGVLAEECGRLLRGFFRAR 723 MDDEGWMRLALEEARAAKAAGEVPVGAVVVRDGEVLARAGNRTRLDCDPTAHAEI VALREAARQLGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRLEVTGGVLAEECGQLMRDFFRAR 724 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALRAAAAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 725 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDATAHAEI LALRAASAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACG SVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFRER 726 MTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLRDPTAHAEIL ALRAACAHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKAGACGS VLDIPGNRRMNHRPEVVGGVLEAECAALMRDFFRER 727 MDPEDLAFMRKALAEARRAAEAGEVPVGAVVVHDGRIVARAHNRREALSDPTAHA EILALREAARALGNYRLAGCTLYATLEPCAMCAGAILHARIARLVYGVPNPKAGACG SVLDVLNHPRLNHRVEVTGGVLAEECGALLRDFFRAR 728 MDPYDLAFMQQALAEARQAKAAGEVPVGAVVVHDGRIVARAHNRTIELSDPTAHA EILALRQAARALGNYRLEGCTLYCTLEPCAMCAGAILHARIERLVYGVPNPKAGAAG SVLNVMNHPRLNHRVEVTGGVLAEECGALLRDFFRAR 729 MDPEDIEFMQKALAEAREAREAGEVPVGAVVVKDGEVVARAHNRVNALSDPTAHA EILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIERLVYGVANPKAGATG SVLNVLNHPRLNHRVEVTGGVLAEECGDLLRDFFRAR 730 MDDRGWMRLALEEARAARARGEVPVGAVVVRDGQVLARAGNRTRELCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCSGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRLEVEGGVLEEECGALLRDFFRAR 731 MDDRGWMRLALEEARASRAAGEVPVGAVVVRDGEVLARAGNRVRELCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVTGGVLEEECGALMRDFFRAR 732 MNDEGFMQLALEEARAARAAGEVPVGAVVVRDGEVIASAGNRTRERCDPTAHAEIV ALRAAARKLGNYRLPGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAGS VLDVLGHPRLNHRMEVEGGVLAEECGRLLRDFFRAR 733 MSDEHFMKQALDEARKAKDRGEVPVGAVVVRDGEIIATGRNRVEELKDPTAHAEM LAITAAAGHLGSKYLTGCTLYVTLEPCVMCAGACIWARVDRVVFGVRNPKAGACGS VFNVPGDPRLNHHPEVTGGILEDECAKLLRDFFRER 734 MSEVDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTA HAEILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPKAGA CGSVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAPRRVFNAQKKAQSSTD 735 MSEVEFSHEYWMRHALTLAKRAWDEREVPVGAVLVHNNRVIGEGWNRPIGRHDPT AHAEIMALRQGGLVMQNYRLIDATLYVTLEPCVMCAGAMIHSRIGRVVFGVRNAKT GAAGSLMDVLHHPGMNHRVEITEGILADECAALLSDFFRMRRQEIKAQKKAQSSTDS GGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFTDEYFMRQALREARRAYDEGEV PVGAVVVRDGRVIARGRNQVERLKDPTAHAEMLALTAAAGHLGSKYLTGCTLYVT VEPCAMCAGALVWARVERVVFGVRNPKAGACGSVFDIPGDRRLNHRPEVVGGVLE AECAALMRDFFREPRRVFNAQKKAQSSTD 736 MDDEGWMRLALEEARAAKAAGEVPVGAVVVRDGQVIARAGNRTRERCDPTAHAEI RALREAARRLGNYRLEGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRLEVTGGVLAEECGQLLRDFFRAR 737 MDDAGWMQLALEEARASRAAGEVPVGAVVVRDGEVLASAGNRTRELCDPTAHAEI VALREAARRLGNYRLSGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVTGGVLAEECAALLRDFFRAR 738 MDDEGWMRLALEEARAARDAGEVPVGAVVVRDGQVIARAGNRTRQLCDPTAHAEI VALRAAARRLGNYRLPGCTLYVTLEPCAMCAGAMVHARIDRLVYGVPNPKAGAAG SVLNVLHHPRLNHRMEVTGGVLAEECGALLTDFFRAR 739 MDDAGWMQLALEEARASKAAGEVPVGAVVVRDGRILARAGNRTRELCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRLEVEGGVLAAECSALLRDFFRAR 740 MSEVEFDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDCDPT AHAEIVALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKA GAAGSVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAPRRVFNAQKKAQSSTD 741 MDDRGWMKLALEEARASRAAGEVPVGAVVVRDGRVLASAGNRTRERCDPTAHAEI VALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAA GSVLDVLGHPRLNHRMEVTGGVLAEECGALLRDFFRAR 742 MDDEGWMQLALDEARKARDAGEVPVGAVVVRDGRVLASAGNRTRERCDPTAHAEI VALREAARKLGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVDNPKAGAAG SVLDVLGHPRLNHRMEVVGGVLAEECGALLRDFFRAR 743 MTDEYFMKQALAEARKAYDAGEVPVGAVVVRDGEVIARGHNRVERLKDPTAHAE MLAITAAAGHLGSKYLEGCTLYVTLEPCVMCAGALVWARVDRVVFGVPNPKAGAC GSVFDIPGDPRLNHRPEVTGGVLEAECAALIRDFFRER 744 MSEVEFTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTA HAEMLALTAAAGHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKA GACGSVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFREPRRVFNAQKKAQSSTD 745 MSEVEFSHEYWMRHALTLAKRAWDEREVPVGAVLVHNNRVIGEGWNRPIGRHDPT AHAEIMALRQGGLVMQNYRLIDATLYVTLEPCVMCAGAMIHSRIGRVVFGVRNAKT GAAGSLMDVLHHPGMNHRVEITEGILADECAALLSDFFRMRRQEIKAQKKAQSSTDS GGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFDEKWMRYALSLADKAEALGEVP VGAVLVKDNQVIGEGWNQSISGHDATAHAEIMAIRDAGKNLQNYRLIDCTLYVTLEP CPMCAGAIVHSRIKRVVFGVSNYKTGAAGSVENLLSNEQLNHQAEVTAGVLAEECG EKISAFFKRPRRVFNAQKKAQSSTD 746 MDDEGWMQLALEEARASRAAGEVPVGAVVVRDGEVVARAGNRTRELCDPTAHAEI VALREAARARGNYRLTGCTLYVTLEPCAMCAGAMIHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRMEVTGGVLAEECGALLRDFFRAR 747 MDDQGWMQLALEEARASRARGEVPVGAVVVRDGEVIARAGNRVRERCDPTAHAEI VALREAARALGNYRLPGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRLEVTGGVLEAECGALLRDFFRAR 748 MDDEGWMRLALEEARASRARGEVPVGAVVVRDGEVLARAGNRTREKCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRMEVVGGVLEAECGALLRDFFRAR 749 MTDEHFMREALREAQKAYDRGEVPVGAVVVRDGEIIARGRNQVEKLKDPTAHAEM LAITAAAGHLGSKYLRGCTLYVTLEPCVMCAGALVWARVERVVFGVDNPKAGAAG SVFNVPGDPRLNHRPEVVGGVLEAECAALLRDFFRER 750 MSEVEFSHEYWMRHALTLAKRAWDEREVPVGAVLVHNNRVIGEGWNRPIGRHDPT AHAEIMALRQGGLVMQNYRLIDATLYVTLEPCVMCAGAMIHSRIGRVVFGVRNAKT GAAGSLMDVLHHPGMNHRVEITEGILADECAALLSDFFRMRRQEIKAQKKAQSSTDS GGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFSDDAGFMREALAEARAAAAAGE VPVGAVVVKDGEIIARAGNRTLRDNDPTAHAEIVALRAAARALGNHRLTGCTLYVTL EPCAMCAGAISHARIARLVYGVDNPKGGAVAHGPRFFAQPTCHHRPEVTGGVGAEE AGALLRDFFRAPRRVFNAQKKAQSSTD 751 MDDEFYMRRALELAALAEEHNEVPVGAVLVLNGEIIGEGWNRSIGHHDATAHAEIM ALRQAGKKLENYRLLDTTLYVTLEPCPMCAGALLHSRVKRVVFGVPNLKAGAAGTV LNLFESQASYHYADVESGLLEQECREQLQAFFKRRRKEKKALKQAQKEAE 752 MDDRGWMRLALEEARAARAAGEVPVGAVVVRDGEVLARAGNRTRELCDPTAHAEI RALREAARQLGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRLEVEGGVLAAECAQLLRDFFRAR 753 MDDAGWMQLALEEARAAREAGEVPVGAVVVRDGEVIARAGNRTRELCDPTAHAEI VALREAARKLGNYRLAGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAA GSVLDVLGHPRLNHRMEVTGGVLAAECGRLLRDFFRAR 754 MDDEGFMQLALEEARAARAAGEVPVGAVVVKDGEVLARAGNRTRELCDPTAHAEI VALREAARALGNYRLSGCTLYVTLEPCAMCAGAMVHARLDRLVYGVPNPKAGAAG SVLDVLHHPRLNHRMEVTGGVLAAECGALLRDFFRAR 755 MSDEHFMRQALEEARKAYDEGEVPVGAVVVRDGEVIARGRNQVEILKDPTAHAEM LALTAAAGHLGSKYLRGCTLYVTLEPCVMCAGACIWARVDRVVFGVRNPKAGAAG SVFDVPGDPRLNHRPEVVGGVLRDECAQLMRDFFRER 756 MSEVEFTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTA HAEMLALTAAAGHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKA GACGSVFDIPGDRRLNHRPEVVGGVLEAECAALMRDFFREPRRVFNAQKKAQSSTDS GGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFTDEYFMRQALREARRAYDEGEV PVGAVVVRDGRVIARGRNQVERLKDPTAHAEMLALTAAAGHLGSKYLTGCTLYVT VEPCAMCAGALVWARVERVVFGVRNPKAGACGSVFDIPGDRRLNHRPEVVGGVLE AECAALMRDFFREPRRVFNAQKKAQSSTD 757 MDEKWMRYALSLADKAEALGEVPVGAVLVKDNQVIGEGWNQSISGHDATAHAEIM AIRDAGKNLQNYRLIDCTLYVTLEPCPMCAGAIVHSRIKRVVFGVSNYKTGAAGSVF NLLSNEQLNHQAEVTAGVLAEECGEKISAFFKRRRKEKKAAKKAAKLAE 758 MNDQGWMRLALEEARAARAAGEVPVGAVVVRDGEVLARAGNRVRLLCDPTAHAE IVALREAARRLGNYRLEGCTLYVTLEPCAMCAGAMIHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRLEVTGGVLADECGALMRDFFRAR 759 MDDEGWMRLALEEARASKAAGEVPVGAVVVRDGEVIARAGNRTRELCDPTAHAEI VALREAARRLGNYRLAGCTLYVTLEPCAMCAGAMIHARLDRLVYGVPNPKAGAAG SVLDVLGHPRLNHRMEVEGGVLAEECRALLTDFFRAR 760 MTDEHFMRQALAEARKAYDEGEVPVGAVVVRDGEIVATGRNQVERLKDPTAHAEM LAITAAAGHLGSKYLRGCTLYVTVEPCVMCAGACVWARVDRVVFGVRNPKAGACG SVFDIPGDPRLNHHPEVTGGVLEDECRQLLRDFFRER 761 MTDEHFMRQALEEARKAYDQGEVPVGAVVVRDGEVIARGRNQVERLKDPTAHAEM LAITAAAGTLGSKYLEGCTLYVTLEPCVMCAGACIWARVERVVFGVRNPKAGACGS VFDIPGDPRLNHRPEVVGGVLEAECAALMRDFFRER 762 MSEVEFSDDAGFMREALAEARAAAAAGEVPVGAVVVKDGEIIARAGNRTLRDNDPT AHAEIVALRAAARALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGVDNPKG GAVAHGPRFFAQPTCHHRPEVTGGVGAEEAGALLRDFFRAPRRVFNAQKKAQSSTD 763 MSEVDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALNDPTA HAEILALREAAKALGNYRLTGCTLYATLEPCPMCAGAILHARIARLVYGVANPKAGA CGTVLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAPRRVFNAQKKAQSSTDSG GSSGGSSGSETPGTSESATPESSGGSSGGSSEVDPTDLAFMREALAEARAAAEAGEVP VGAVVVCDGRIVARAHNRPIALNDPTAHAEILALREAAKALGNYRLTGCTLYATLEP CPMCAGAILHARIARLVYGVANPKAGACGTVLDVMNHPRLNHRVEVTGGVLAEEC GALLSGFFRAPRRVFNAQKKAQSSTD 764 MDDAGFMREALAEARAAAAAGEVPVGAVVVKDGEIIARAGNRTLRDNDPTAHAEIV ALRAAARALGNHRLTGCTLYVTLEPCAMCAGAISHARIARLVYGVDNPKGGAVAHG PRFFAQPTCHHRPEVTGGVGAEEAGALLRDFFRAR 765 MDDEGWMRLALEEARKSRAAGEVPVGAVVVRDGEVLATAGNRTRELCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMIHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVEGGVLEAECAALLRDFFRAR 766 MDDEGWMQLALEEARQSRAAGEVPVGAVVVRDGEVIARAGNRTREKCDPTAHAEI VALREAARKLGNYRLPGCTLYVTLEPCAMCAGAMVHARLDRLVYGVANPKAGAA GSVLDVLHHPRLNHRMEVTGGVLAEECGALLRDFFRAR 767 MDDAGWMRLALEEARKSRARGEVPVGAVVVRDGQVLARAGNRTRELCDPTAHAEI VALRAAARKLGNYRLPGCTLYVTLEPCAMCAGAMVHARLDRLVYGVRNPKAGAA GSVLDVLGHPRLNHQMEVTGGVLADECAALLRDFFRAR 768 MSEVEFDDAGFMRLALEEARAAAAAGEVPVGAVVVRDGEVLARAGNRTVRDNDPT AHAEIVALREAARRLGSYRLAGCTLYVTLEPCPMCAGAMIHARLDRLVYGVANPKA GAAGTVLDVLGHPRLNHRMEVEGGVLAAECGALLRDFFRAPRRVFNAQKKAQSSTD SGGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFDDAGFMRLALEEARAAAAAGE VPVGAVVVRDGEVLARAGNRTVRDNDPTAHAEIVALREAARRLGSYRLAGCTLYVT LEPCPMCAGAMIHARLDRLVYGVANPKAGAAGTVLDVLGHPRLNHRMEVEGGVLA AECGALLRDFFRAPRRVFNAQKKAQSSTD 769 MDDAGFMELALDEARAARAAGEVPVGAVVVRDGEVLARAGNRTRELCDPTAHAEI VALREAARKLGNYRLEGCTLYVTLEPCAMCAGAMLHARLDRLVYGVANPKAGAAG SVLDVLGHPRLNHRMEVTGGVLEDECAALLRDFFRAR 770 MDDAGWMQLALEEARAARAAGEVPVGAVVVRDGEVLARAGNRTRERCDPTAHAE IVALRAAARHLGNYRLEGCTLYVTLEPCAMCAGAMLHARLDRLVYGVDNPKAGAA GSVLDVLGHPRLNHRLEVTGGVLADECGQLLRDFFRAR 771 MNDKGWMRLALEEARAARAAGEVPVGAVVVRDGEVIAAAGNRRRELCDPTAHAEI VALREAARRLGNYRLPGCTLYVTLEPCAMCAGAMIHARLDRLVFGVANPKAGAAGS VLDVLGHPRLNHRLEVTGGVLEEECGQLLRDFFRAR 772 MSDEHFMQQALAEARKAYDLGEVPVGAVVVRDGRIIARGHNQVEKLKDPTAHAEM LAITAAAGHLGSKYLEGCTLYVTLEPCIMCAGACVWARVERVVYGVRNPKAGACGS VFDIPGDPRLNHHPEVTGGVLEAECARLMRDFFRER 773 MSDEFFMKQALEEARLAYDEGEVPVGAVVVRDGEVIARGRNQIEELKDPTAHAEML AITAAAGHLGSKYLLGCTLYVTLEPCVMCAGACVWARVDRVVYGVRNPKAGAAGS VFDIPGDPRLNHHPEVVGGVLQAECAALMRDFFRER 774 MSEVEFSHEYWMRHALTLAKRAWDEREVPVGAVLVHNNRVIGEGWNRPIGRHDPT AHAEIMALRQGGLVMQNYRLIDATLYVTLEPCVMCAGAMIHSRIGRVVFGVRNAKT GAAGSLMDVLHHPGMNHRVEITEGILADECAALLSDFFRMRRQEIKAQKKAQSSTDS GGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFDDAGFMRLALEEARAAAAAGEV PVGAVVVRDGEVLARAGNRTVRDCDPTAHAEIVALREAARRLGNYRLAGCTLYVTL EPCAMCAGAMIHARLDRLVYGVANPKAGAAGSVLDVLGHPRLNHRMEVEGGVLAA ECGALLRDFFRAPRRVFNAQKKAQSSTD 775 MSEVEFTDEYFMRQALREARRAYDEGEVPVGAVVVRDGRVIARGRNQVERLKDPTA HAEILALRAACRHLGSKYLTGCTLYVTVEPCAMCAGALVWARVERVVFGVRNPKA GACGSVLDIPGDRRLNHRPEVVGGVLEAECAALMRDFFREPRRVFNAQKKAQSSTDS GGSSGGSSGSETPGTSESATPESSGGSSGGSSEVEFTDEYFMRQALREARRAYDEGEV PVGAVVVRDGRVIARGRNQVERLKDPTAHAEILALRAACRHLGSKYLTGCTLYVTV EPCAMCAGALVWARVERVVFGVRNPKAGACGSVLDIPGDRRLNHRPEVVGGVLEA ECAALMRDFFREPRRVFNAQKKAQSSTD 776 MDPTDLAFMREALAEARAAAEAGEVPVGAVVVCDGRIVARAHNRPIALSDPTAHAE ILALREAARALGNYRLTGCTLYATLEPCAMCAGAILHARIARLVYGVANPGTGACGS VLDVMNHPRLNHRVEVTGGVLAEECGALLSGFFRAR

[0159] The scope of the present invention is not limited by what has been specifically shown and described hereinabove. Those skilled in the art will recognize that there are suitable alternatives to the depicted examples of materials, configurations, constructions, and dimensions. Variations, modifications, and other implementations of what is described herein will occur to those of ordinary skill in the art without departing from the spirit and scope of the invention.

[0160] Numerous references, including patents and various publications, are cited and discussed in the description of this invention. The citation and discussion of such references is provided merely to clarify the description of the present invention and is not an admission that any reference is prior art to the invention described herein. All references cited and discussed in this specification are incorporated herein by reference in their entirety.