Genomic nucleic acids, cDNA and mRNA which code for polypeptides with IL-16 activity, processes for the production thereof and their use

The invention concerns regulatory elements of the expression of IL-16, genomic nucleic acids, cDNA and mRNA that code for polypeptides with IL-16 activity, processes for the production thereof and their use.

IL-16 (interleukin-16) is a lymphokine that is also denoted “lymphocyte chemoattracting factor” (LCF) or “immunodeficiency virus suppressing lymphokine” (ISL). IL-16 and its properties are described in WO 94/28134, the International Application PCT/EP96/01486 as well as by Cruikshank, W. W., et al., Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 5109-5113 and Baier, M., et al., Nature 378 (1995) 563. The recombinant production of IL-16 is also described therein. According to this IL-16 is a protein with a molecular mass of 13,385 D. Cruikshank also found that ISL elutes as a multimeric form with a molecular weight of 50-60 or 55-60 kD in molecular sieve chromatography. The chemoattractant activity is attributed to this multimeric form which is a cationic homotetramer (product information AMS Biotechnology Ltd., Europe, Cat. No. 11177186). Baier describes a homodimeric form of IL-16 with a molecular weight of 28 kD. However, the chemoattractant activity described by Cruikshank et al., in J. Immunol. 146 (1991) 2928-2934 and the activity of recombinant human IL-16 described by Baier are very low.

The object of the present invention is to provide regulatory elements of IL-16 expression, to improve the activity of IL-16 and to provide forms of IL-16 which exhibit low immunogenicity and are advantageously suitable for therapeutic use.

The object of the invention is achieved by a nucleic acid with which expression of a polypeptide having interleukin-16 activity can be achieved or regulated in a eukaryotic host cell, wherein the said nucleic acid

a) corresponds to the DNA sequence SEQ ID NO:1 or its complementary strand;

b) hybridizes under stringent conditions with the DNA of sequence SEQ ID NO:1, preferably with nucleotides 1-6297 of SEQ ID NO:1;

c) or is a nucleic acid sequence which, if there was no degeneracy of the genetic code, would hybridize under stringent conditions with the nucleic acid sequences defined by a) or b),

d) and, if it codes for a polypeptide having IL-16 activity, has a length of at least 1179 coding nucleotides.

A preferred sequence is the cDNA sequence shown in SEQ ID NO:6, the complementary strand thereof or a sequence which under stringent conditions hybridizes with the sequence SEQ ID NO:6. SEQ ID NO:5 and the plasmid pCI/IL16 PROM also describe the genomic DNA of IL-16 and contain the introns and exons each parity or completely.

Such a nucleic acid preferably codes a polypeptide with IL-16 activity, particularly preferably the natural IL-16 of primates such as human IL-16 or IL-16 of a species of monkey or another mammal such as e.g. mouse.

It surprisingly turned out the FIG. 2 of WO 94/28134 does not describe the complete sequence of IL-16. The start codon “ATG” of the precursor form of the protein does not begin with nucleotide 783. The sequence has yet more differences to FIG. 2 of WO 94/28134. These are for example nucleotide substitutions (313 G by A, 717 C by A, 1070 G by T).

The sequence of IL-16 can differ to a certain extent from protein sequences coded by such DNA sequences. Such sequence variations can be amino acid substitutions, deletions or additions. However, the amino acid sequence of IL-16 is preferably at least 75% especially preferably at least 90% identical to the amino acid sequence of IL-16. Variants of parts of the amino acid sequence or nucleic acid sequence are for example described in the International Patent Application Nos. PCT/EP96/01486, PCT/EP96/05662 and PCT/EP96/05661.

Nucleic acids within the sense of the invention are for example understood as DNA, RNA and nucleic acid derivatives and analogues. Preferred nucleic acid analogues are those compounds in which the sugar phosphate backbone is replaced by other units such as e.g. amino acids. Such compounds are denoted PNA and are described in WO 92/20702. Since for example PNA-DNA bonds are stronger the DNA-DNA bonds the stringent conditions for PNA-DNA hybridization described in the following are not applicable. Suitable hybridization conditions are, however, described in WO 92/20703.

SEQ ID NO:6 describes the cDNA derived from the mRNA. The cDNA is suitable, for instance, for the determination of the corresponding RNA in tissue fluids and body fluids of mammals and humans. The cDNA is preferably used, however, for the expression of full length IL-16 in prokaryotes, preferably in E.coli. For that purpose the cDNA is inserted into an appropriate vector, transformed into a prokaryotic host cell, said host cell is cultivated, and, after cultivation, IL-16 is isolated. This can be done according to the methods known to one skilled in the art. If the protein is not secreted but obtained within the cell as a denatured insoluble protein (inclusion bodies), solubilisation and naturation must be carried out thereafter. These methods are also known to one skilled in the art.

SEQ ID NO:7 describes the amino acid sequence of IL-16 in its precursor form, which is also a subject matter of the invention.

The term “IL-16” within the sense of the invention is understood as a polypeptide with the activity of IL-16. IL-16 preferably exhibits the effect stated in the International Patent Application No. PCT/EP96/01486 or it stimulates cell division according to WO 94/28134.

IL-16 binds to CD4 + lymphocytes and can suppress the replication of viruses such as for example HIV-1, HIV-2 and SIV. The function of IL-16 is not limited by its presentation in the MHC complex.

IL-16 in particular exhibits one or several of the following properties:

binding to T cells via the CD4 receptor,

stimulating the expression of the IL-2 receptor and/or HLA-DR antigen on CD4 + lymphocytes,

stimulating the proliferation of T helper cells in the presence of IL-2,

suppressing the proliferation of T helper cells stimulated with anti-CD3 antibodies,

suppressing the replication of viruses preferably HIV-1, HIV-2 or SIV.

The term “hybridizing under stringent conditions” means that two nucleic acid fragments hybridize with one another under standardized hybridization conditions as for example described in Sambrook et al., “Expression of cloned genes in E. coli” in Molecular Cloning: A laboratory manual (1989), Cold Spring Harbor Laboratory Press, New York, U.S.A. Such conditions are for example hybridization in 6.0×SSC at about 45° C. followed by a washing step at 2×SSC at 50° C. To select the stringency, the salt concentration in the washing step can be selected for example between 2.0×SSC at 50° C. for low stringency and 0.2×SSC at 50° C. for high stringency. In addition the temperature in the washing step can be varied between room temperature ca. 22° C. for low stringency and 65° C. for high stringency.

A “regulatory element” is understood as a DNA sequence which regulates the expression of genes (e.g. promoter, attenuator, enhancer). A promoter is understood as a cis-acting DNA sequence which is usually 80-120 base pairs long and is located 5′ upstream of the initiation site of the gene to be expressed. A promoter is in addition characterized in that RNA polymerase can bind to it and can initiate the correct transcription. A preferred DNA fragment with promoter activity spans nucleotides 2053-3195 of SEQ ID NO:1.

An enhancer is usually understood as a cis-acting DNA sequence of ca. 50-100 bp in length which is of paramount importance for an efficient transcription. Enhancer sequences work independently of orientation and position.

An intron is understood as a nucleotide sequence which is present in eukaryotic genes and is transcribed into pre-mRNA and is removed from the mRNA in a further step (splicing). The IL-16 gene contains several introns and exons which are described in SEQ ID NO:1, pCI/IL16 PROM and/or SEQ ID NO:5.

Plasmid pCI/IL-16 PROM contains a sequence upstream of SEQ ID NO:5. SEQ ID NO:5 describes the 3′ terminal part of the genomic DNA whereas the plasmid describes the 5′ terminal part. Both sequences overlap in the region of nucleotide 1 to nucleotide 87 of SEQ ID NO:5. Thus the plasmid contains the IL-16 sequence 5′ upstream of nucleotide 87 of SEQ ID NO:5. These are coding sequences and regulatory elements as well as one or several introns. In the first intron of SEQ ID NO:5 about 600 base pairs are missing at the position denoted “N”. These nucleotides can either be deleted or filled up by any nucleotides. However, it is important that the intron/exon junctions remain correct. The order of these base pairs is shown in SEQ ID NO:1.

A further subject matter of the invention are regulatory elements of the expression of IL-16 (in particular promoter and enhancer elements as they are present on the plasmid pCI/IL-16 PROM or in SEQ ID NO:1/SEQ ID NO:5 or can be derived therefrom). Promoter elements are at the 5′ end upstream of exon 1. The enhancer elements are on the 5′ side of the IL-16 gene to be expressed in the said plasmid as well as at the 3′ end of SEQ ID NO:1/SEQ ID NO:5.

The regulatory elements according to the invention are particularly suitable for the expression of polypeptides with IL-16 activity in eukaryotic cells. The regulatory elements are, however, also suitable for expression of other genes in eukaryotic cells. The regulatory elements are particularly advantageous for expression in lymphocytes in particular in T lymphocytes and cells or cell lines derived therefrom. Suitable regulator sequences can be selected as described in example 7.

IL-16 is preferably recombinantly produced in eukaryotic host cells. Such production methods are known to a person skilled in the art and are for example described in EP-B 0 148 605. However, in order to obtain the forms of IL-16 according to the invention by recombinant production in a defined and reproducible manner, additional measures have to be taken beyond the processes for recombinant production familiar to a person skilled in the art. For this a DNA is firstly prepared which is able to produce a protein that has the activity of IL-16. The DNA is cloned into a vector that can be transferred into a host cell and can be replicated there. Such a vector contains regulatory elements that are necessary to express the DNA sequence in addition to the IL-16 sequence. One or several regulatory elements contained in SEQ ID NO:1 are preferably used. Such a nucleic acid which contains the regulatory elements is transferred into a vector which is capable of expressing the DNA of IL-16. The host cell is cultured under conditions that are suitable for vector amplification and IL-16 is isolated. In this way suitable measures ensure that the protein can adopt an active tertiary structure in which it exhibits IL-16 properties.

A lymphoid expression cell line is preferably used instead of the usual host cells (COS, CHO). In this connection IL-16 may be processed into the active shortened form.

In this process it is not necessary that the expressed protein contains the exact IL-16 amino acid sequence from SEQ ID NO:7. Proteins are equally suitable which contain essentially the same sequence and have analogous properties. A eukaryotic expression using the regulatory elements and/or the genomic DNA of IL-16 ensures that IL-16 is correctly processed. In this way a protein is obtained in a recombinant manner which is essentially or completely identical to natural IL-16.

The nucleic acid sequence of the protein can be modified. Such modifications are for example:

Modification of the nucleic acid in order to introduce various recognition sequences of restriction enzymes to facilitate the steps of ligation, cloning and mutagenesis

modification of the nucleic acid to incorporate preferred codons for the host cell

extension of the nucleic acid by additional operator elements in order to optimize the expression in the host cell.

In addition the expression vectors usually contain a selectable marker in order to select the transformed cells. Such selectable markers are for example the DHFR gene, the resistance genes for ampicillin, chloroamphenicol, erythromycin, kanamycin, neomycin and tetracyclin (Davies et al., Ann. Rev. Microbiol. 32 (1978) 469). Selectable markers which are also suitable are the genes for substances that are essential for the biosynthesis of substances necessary for the cell such as e.g. histidine, tryptophan and leucine.

Further genetic engineering methods for the construction and expression of suitable vectors are described in J. Sambrook et al., Molecular Cloning: A laboratory manual (1989), Cold Spring Harbor Laboratory Press, New York, N.Y.

Recombinant IL-16 can be expressed in eukaryotic cells such as for example CHO cells, yeast or insect cells. CHO cells, COS cells or host cells derived from lymphocytes (preferably from T lymphocytes) are preferred as the eukaryotic expression system. Expression in yeast can be achieved by means of three types of yeast vectors: integrating YI P (yeast integrating plasmids) vectors, replicating YR P (yeast replicon plasmids) vectors and episomal YE P (yeast episomal plasmids) vectors. More details of this are for example described in S. M. Kingsman et al., Tibtech 5 (1987) 53-57).

A further subject matter of the invention is a eukaryotic host cell which is transformed or transfected with a nucleic acid that codes for an IL-16 polypeptide according to the invention in such a way that the host cell expresses the said polypeptide. Such a host cell usually contains a biological functional nucleic acid vector, preferably a DNA vector e.g. a plasmid DNA that contains this nucleic acid.

A further subject matter of the invention is human interleukin-16 or interleukin-16 from primates preferably human IL-16 which can be obtained essentially free of other human proteins as a correctly processed product of a eukaryotic expression. IL-16 is a protein that occurs as a monomer or as a multimer composed of monomeric IL-16 (denoted subunits in the following). The molecular weight of a monomeric IL-16 subunit is preferably ca. 14 kD. In addition a monomeric IL-16 polypeptide is preferred which cannot be cleaved into further subunits.

It surprisingly turned out that the nucleic acid and protein sequence of IL-16 described in WO 94/28134 do not correspond to the natural human sequences. This is merely an IL-16 fragment. However, for therapeutic use it is preferable to use a correctly processed protein which is either identical to the natural protein or only differs slightly from the natural protein and exhibits at least a comparable activity and hence low immunogenicity.

Within the sense of the invention the nucleic acid sequence of IL-16 can contain deletions, mutations and additions. An IL-16 (monomeric form, subunit) that is coded by such a nucleic acid can be multimerized in a preferred embodiment. In this way the activity of IL-16 can be increased. Such multimeric forms are preferably dimeric, tetrameric or octameric forms.

In a further preferred embodiment polypeptides of the invention can additionally contain a defined content of metal ions wherein the number of metal ions per subunit is preferably 0.5 to 2.

Within the sense of the invention many metal ions are suitable as the metal ions. Alkaline earth metals as well as elements of side groups have proven to be suitable. Particularly suitable are alkaline earth metals, cobalt, zinc, selenium, manganese, nickel, copper, iron, magnesium, potassium, molybdenum and silver. The ions can be monovalent, divalent, trivalent or quadrivalent. Particularly preferred are divalent ions. The ions are preferably added as solutions of MgCl 2 , CaCl 2 , MnCl 2 , BaCl 2 , LiCl 2 , Sr(NO 3 ) 2 , Na 2 MoO 4 , AgCl 2 .

Such multimeric forms and forms of IL-16 containing metal ions are described in the International Patent Application No. PCT/EP96/05661.

The polypeptide according to the invention can be produced in such a way that a eukaryotic host cell which is transformed or transfected with a nucleic acid according to the invention is cultured under suitable nutrient conditions and the desired polypeptide is optionally isolated. If the polypeptide is to be produced in vivo as part of a gene therapy treatment, the polypeptide is of course not isolated from the cell.

In addition the invention concerns a pharmaceutical composition which contains a polypeptide according to the invention in an adequate amount and/or specific activity for a therapeutic application as well as optionally a pharmaceutical suitable diluent, adjuvant and/or carrier.

The polypeptides according to the invention are particularly suitable for the treatment of pathological states that have been caused by viral replication especially retroviral replication and for immunomodulation. Such therapeutic applications are also described in WO 94/28134 as well as in the International Patent Application No. PCT/EP96/01486. Diagnostic test procedures are also described in the latter.

The polypeptides according to the invention can preferably be used for immunosuppression. This immunosuppression is preferably achieved by inhibiting the helper function of TH O and/or TH 1 and TH 2 cells. The polypeptides according to the invention are therefore of therapeutic value in all diseases in which an immunodys-regulatory component is postulated in the pathogenesis, in particular a hyperimmunity. Diseases which can be treated with IL-16 can be diseases in cardiology/angiology such as myocarditis, endocarditis and pericarditis, in pulmonology these are for example bronchitis, asthma, in hematology autoimmune neuropenia and graft rejection, in gastroenterology chronic gastritis, in endocrinology diabetes mellitus type I, in nephrology glomerulonephritis, diseases in the field of rheumatoid diseases, diseases in opthalmology, in neurology such as multiple sclerosis, in dermatology such as eczema. The polypeptides according to the invention can in particular be used in autoimmune disease, allergies and to avoid graft rejections.

A further subject matter of the invention is the use of nucleic acids according to the invention in the field of gene therapy. Vector systems that are suitable for this are for example retroviral or non-viral vector systems.

The following examples and publications as well as the sequence protocol are intended to elucidate the invention, the scope of which is characterized by the patent claims. The methods described are to be understood as examples which also after modifications still describe the subject matter of the invention.

The plasmid pCI/IL 16 PROM was deposited on the 26.03.96 under the No. DSM 10603 at the “Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSM)”, Mascheroder Weg 1b, D-38124 Braunschweig.

General

Cells

Human peripheral blood mononuclear cells (PBMC) were isolated by Ficoll Hypaque gradient centrifugation and cultivated in RPM 1640 medium supplemented with 20% fetal calf serum, 100 units/ml IL-2 and 5 μg/ml phytohemagglutinin (PHA). T lymphocyte subsets were prepared as described by Ennen, J., et al., Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 7207-7211.

RNA preparations and Northern blotting

Total RNA was extracted using the RNA-Isolation Kit (Stratagene, La Jolla, U.S.). Poly (A + ) RNA was isolated from total RNA with the Oligotex-dT mRNA system (Qiagen, Hilden, DE). 10 μg of total RNA or 2 μg of Poly (A + ) RNA were loaded on a formaldehyde agarose gel and after electrophoresis blotted onto a positively charged nylon membrane (Boehringer Mannheim GmbH, DE). The IL-16 cDNA probe was generated using the PCR DIG-probe synthesis system (Boehringer Mannheim GmbH, DE) and spans the IL-16 cDNA region from nucleotide 1693 to the end of the reading frame at nucleotide 2082. Hybridizations were carried out at 58° C. overnight followed by several high stringency washes. For detection of the signals the DIG luminescent system (Boehringer Mannheim GmbH, DE) was employed according to the manufacturer's recommendations. The quality of RNA preparations was routinely assessed by hybridization with a 13-actin probe. The Human RNA master blot (Clontech Laboratories, Palo Alto, U.S.) was analysed with the same IL-16 cDNA hybridization probe under comparable conditions.

Reverse transcription and PCR

Identification of the 5′ end of IL-16 precursor mRNA was performed using the 5′ RACE system for rapid amplification of cDNA ends (Life Technologies, Gaithersburg, U.S.). Additional RACE experiments were carried out with parts of the CapFinder system and Marathon-Ready cDNAs from human lymph nodes, leukocytes and murine leukocytes respectively (all from Clontech Laboratories, Palo Alto, U.S.). All other cDNAs were synthesized using up to 5 μg of total PBMC RNA and oligo-dT as primer (Pharmacia, Uppsala, SE).

Gel purified PCR products were ligated into the pGEM-T vector (Promega, Madison, U.S.) before determination of the nucleotide sequences according to standard methods.

Peptides and antibodies

Antibodies specific for pro-IL-16 coupled to KLH via disulfide bonds were raised in rabbits. The antisera and the peptides were obtained from the Custom peptide antibody production program (Eurogentec, Seraing, BE). Recombinant IL-16 (rIL-16His) was used to raise antisera in goats (Baier, M., et al., Nature 378 (1995) 563). Affinity purified goat anti-IL-16 antibodies were used at an IgG concentration of 0.25 μg/ml in immunoblot experiments.

Immunoblots

Cell lysates were prepared by incubation of 2.5×10 7 cells in 400 μl of solubilization buffer (20 mM Tris HCl, pH 7.5, 1% NP-40, 150 mM NaCl, 5 mM EDTA, 1 mM phenylmethyl-sulfonyl-fluoride, 10 mM sodium fluoride, 1 mM sodium pyrophosphate, 5 μg/ml aprotinin and 5 μg/ml leupeptin) for 15 minutes on ice. Nuclei were removed by centrifugation and the volume was finally adjusted to 500 μl with 4×SDS sample buffer. Immunoblots were carried out according to standard protocols. Antisera were used at appropriate dilutions in blocking buffer (phosphate buffered saline (PBS), pH 7.2, 5% Marvel). Finally, bound antibody was detected using the enhanced chemoluminescence (ECL) kit (Amersham, Little Chalfont, UK).

Proteolytic cleavage of pro-IL-16 in cell lysates

Purified CD8(+) cells were lysed after cultivation for 2 days by incubation in PBS-Dulbecco/1% NP-40 for 10 minutes on ice. Lysates were clarified by centrifugation and finally diluted 1:5 in PBS. The equivalent of 4.5×10 6 cells was incubated with 30 μg rIL-16His in a volume of 66 μl for 1648 hours at room temperature. Thereafter, the cleavage of rIL-16His was analysed by immunoblotting with 1:100 diluted serum 802, which recognizes the carboxyterminus of IL-16.

Baier, M., et al., Nature 378 (1995) 563

Cruikshank, W. W., et al., J. Immunol. 146 (1991) 2928-2934

Cruikshank, W. W., et al., Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 5109-5113

Davies et al., Ann. Rev. Microbiol. 32 (1978) 469

deWet, J. R. et al., Mol. Cell. Biol. 7 (1987) 725-737

Ennen, J., et al., Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 7207-7211

European Patent No. 0 148 605

Patent Application No. PCT/EP96/01486

International Patent Application No. PCT/EP96/05661

International Patent Application No. PCT/EP96/05662

Kingsman, S. M., et al, Tibtech 5 (1987) 53-57

Mack et al., Analyt. Biochem. 200 (1992) 74-80

Sambrook et al., “Expression of cloned genes in E. coli” in Molecular Cloning: A laboratory manual (1989), Cold Spring Harbor Laboratory Press, New York, U.S.A.

WO 92/20702

WO 92/20703

WO 94/28134

Zhu, Y., et al., Clontechniques 11 (1996) 30-31

CTGGTACTTT CATGTACATT GTGTCAATTA AATCTTACAA CCACCTGATG GTGAGAGTCC 60

CAGTTGTGCA AAGAGGGAAC TGAGAAACTC GCTCAAGTTC ACATTGCTAG TGGGTCACAG 120

TTACCCACTA TGCAATGCTG AGTTTCCCAT CCTTACCCAG AAGCTGTCTC CCCCATCACG 180

GAATGGCCCT GCAGGGGCCT TGGCCCTTCC CTTAAGCACA CCGTGGGCAG GTGGGAGGGG 240

GCCTCTGGAA ATCCCCTAAA ACAATCTACA GTGAGGGTTG GCAAGCTTCA GGAGGGGTAG 300

CGGTGGAGAC GGGATGTTGA GTAGGAGGGG TGAAAGTGAA GGAGGGAGGA GGAAGTCAGG 360

TTACTAAAAA GGAAGTGCAG TTTTGCAGAG CGCTGGCAGG ATGTGGCTGG TTAGCAACAC 420

ATGATGGAGT TATCAGATGG ATCTGTTCTC CCACCCCCTC TTTTAAGCCC ATATTTCATT 480

TTCCCTTGGG CCTGAGACCT ATGAGTCCAG AAGGGCAAAT CAGGAGCAGC CAGCTGAGAA 540

GCCAGTCATT TTGCCTTCCT CCTGGAGGCC CAGAAAAGGA GTGCAGTTGC CACAGCAGGT 600

CTGTCCCAGT GATGCCCTTG GCAGAGCCAC ATAGGGTCAG GGAATATTCC CGAGTAAGGC 660

GTCTGGAGAA GGAACTGGGG TGTCCTCAGG GAAGCCCAGG CAAGGAACTT CCCACAGGTC 720

ATCTTTCATG CCCTGTGTGC CTCAGCAGAA TACAGGGCTC CCTCCTGTAC CTGCCCCCAA 780

CAGCACCGTC TCCTGGAGAC AAGGCCGTTC TGCAGCTGCC CTCCTCTGTT TGCTCTGGTC 840

TGTCCCACGT GGCCAGCAGA TCCTTCTCCC ACAAACATTT CCATAAAAGC AATCAGCACG 900

ACATAATTTT ATTGGGCACT GGAGAGGCGG GGGTCACAGA GAAAGGATCA TAGCACGCAA 960

TAGAAAACAG GAAGCAATTT GCTTGAGGTC ACTCTCAAAA TTTCCTTGAC CATTCCTGGG 1020

GATTTCTCAC TGGATGTTTT CTTCCGTGGC CACAGTGTCC ACTGTCTCAC TCTCCCACTT 1080

TTCCCTCCCT GCAGTCTTTT CTCTACAGGG TCCCAAGACT GTTGTCAAGC TGCTATGGAT 1140

GACCCCCAAG TCTTTCCCAT CTACTCTAAT TCAAGGGGAC TTAACTCTCA CAACCAATAT 1200

GAACTTTGGG ATATTTTCTT CAACAAAAAA CTAACATCCC TCTTATAAAA AATCAGCCTA 1260

AACTCTCCCC CGTGCTTTAA AAAACTTGCT TAAAAAAACA CAACAGGATT TTCGAAGAAT 1320

CCTTTCTTAG AAAACAAACA AAAAACCAAA CAAAAACGTA CTTTCTCCCC ACTATGCTGA 1380

ATCTGCTCTC TCCCTCTTTC CTTCTTTCTC TTCTCCCTCC CTCATCCACC AAGCATGGTT 1440

CCAGGAAACA CTAGTAAGAG AAAAATTTGT GTAAAATCAA ATTTATTTCA GGGGCTAATT 1500

CTGAAGTCTC CCATGAAGAG GATGCAATAT TGGATGTGTT GATGAAAAGA CAAAACACAT 1560

TTGTGCTGTT CTAAGTTGTA AAGCTGCATT GACTGCAGTT GGTATCACAT GTGGCTGCCT 1620

GTAAAAGAGC TAACAATCCA TGAATGTCAA CAGATGTCAA CTTACAGAGC TCCCAACCAG 1680

GTGAAATTAA ATTTCATCCC CATGTAATTT CTCTTGTGGA CAAGAGACTT AGAGATCATC 1740

AGGCCAATAT TTGGAGCTTC TAATGCCATG ACTCAGCCTT ACTTTTTTTA AGGGCTAGTT 1800

CGAGAAGCTC AATGATTCCT TTGAAATTGG TTGATCTCTC AGTATTTCAT AATGCTCTCC 1860

TAAAGCTCAG TTCTACAGTA GGGAACTCGA GCTGAGGCAA TGCTCTGTGA ATACACTTCT 1920

AACTTTTGTA GACCTTTGCT TCCTCCAAAA TGTTTATTGT CAATGTAGAT CTTAAATTTC 1980

AGGTCATGGA TATTTGCCAT TGCTTTTTTA GTCCCAAAGG ATGCATTTGT TCCTTCCTCT 2040

TTCCTTCCTC TCTGGAAGGA AGCCTGCAGC CATGTCAAAT GGCCCATCAT TACACAAATC 2100

TGGAATGAAC CGGACGTGGA GGCCACCGCA GTATAGCAAA GCATTTCTCT TGCAGACAAT 2160

CAAATACAGG TGGCATCATT TTGATGATGT CTGCTTTCTC AATCTTTTTT TCCAGATGGG 2220

TATTATGTTT GGTTGGGCTA TGTCTCTGGA ACACTATTTT TCTGCCTCTC TGCCTGCAAA 2280

ATTCTTACTC TGTTTATGAA GCAGACAGAA AGTACTTCTC TAGGAAGCCT TCTCCACCTC 2340

TGGGATGGAA CTGGTCTCTC TGTTTCCTCT GGGCCCTGAC AGTACCTTAA GCACACTGTG 2400

TGATAATCCA AACTCTTCAA GTATTGCATA GCTATTCAGA GCCTGGTTCA TCTTGTCCCT 2460

AGGCTGTTTT GGGAGGACCC CAAGGCTGCA TCCAGGCTCA GTGGTGGAAA CAATTCTGCA 2520

ACAGATTGAG GATGTCACCC TAGGTGCCAC AGAGGGGAGC AATGGCACAG GTGCTGAGTA 2580

TCTGTCATCT TTTGCAGAAC ACTTACTAAA TATTTGAAGA GTGCTTAACA AGTGACAGCA 2640

ATTGACAAGC ATTTTCCTGA GTGCTCTAAC CTTAGGGAAC ACTAGCTGCC AGGTTTTTTT 2700

GCTGCCTTGT TTCTACGCTG CCCTATACCC TCCCGGGGTG GGTAGTTCAC CAGATGCAGT 2760

TGTAACTGAA GCAATGCCAG TCCCTCCACA CTCAAAGCCT TTTGTTCCTA TCATAAAGAG 2820

TCAGGGTCTT CAAGTATGTC AACAGTATGA GCCCATGACC TGGATACCAG GTTGCTGGAA 2880

GTCAAGGGGT GCTCTGCATG TCTAGGAGGT GCTGGCTCTG CCACGTCAGC ACCAAGGAGA 2940

AAAGAATCCT CTTTACATGG CTGCTGATGA ACTTCTCACT GAAAGCAGCT CAATATCCGT 3000

TTTTCCGTCC CAATCAAAGC GTGTCTCGCC TTCTCACAGC TTGAGGCTAC CGTTTTGACA 3060

TGGTCTCGCT TCCTGTTTAC ACCACAGGAA GCGAGAGAGC TGCTGCCACT GCTGCTACCA 3120

CAGGAAGACA CAGCAGGGAG AAGCCCTAGT GCCTCTGCCG GCTGCCCAGG ACCTGGTATC 3180

GGCCCACAGA CCAAGTCCTC CACAGAGGGC GAGCCAGGGT GGAGAAGAGC CAGCCCAGGT 3240

AAGCTTTCAT TGAGATCTTC CAAAAGAAAG GGTCTTTTGA AAAAAGGTGC AGGGATAAGA 3300

TAAGAGCACA AATTGGCCTG AGGATCAGAG TGCTCTGCTT TGACATCACC ACTGGACCTG 3360

GCTGATCAAC AGTCAAGGGT TCCAGGTGCT GGGCAGCAGC ACCGTGGAGG TGCTGTCCAG 3420

GGTGGGGAGC CTCCTGGGTG GACGGGTGAT GCTGTGGGGG TGGCAGCAGG AATGCAGGCC 3480

ATTCTGGATA ATTGGGAGGA TGGAGCCCTT GGAAGAGGTC CAAAGACACA CCCACCCAGC 3540

CATCCTGGGC AGCTACCTCT AGGGTGCCAA CATTCCAGTT GCAACAGTCC TGCTGCATTC 3600

AGGATTTCTG AGTCAGAGAA TGCAACGCCA GAAAAGTATA AATAGCATCT ACCAGTGGTC 3660

ACCTCCTCCA TGAGGTGGAT AGCAAGGGTG TGTCCACATG GTACACCTGA CAATGCTAAG 3720

ACATGACTTG AATATTTATT TGCTTGCTAG AGAGAGCATA GGACTTGAAG TCAGGGAATC 3780

CTGGATCTGT CTGTCATTAG TATGATTCTG AGCAACCTAC TTTGCCTTTC TGAGCCCAGA 3840

TTCACTCATC AGCAATGTGT GGAAGAGCAC GTAGACCCCA AGCATATGAT GCATTCAGCA 3900

AGCACACATT GAATGCTGGC TTCGTGAGGC CCTGTGCTAG GTGCTGGGGG GAGAGAGAGA 3960

AAGGGATGAG ACCAGGTAGT CAGGTCCTGC CTCCAAGGAG CAACTAGTAG TGGCAGGAAA 4020

TAAACATATA GACTATAAAA CATATGACTG TTTGAGTAAC ACTACAGAAA AGCTCATGAA 4080

AGACTTTTGG AGGGCTAAGG GACATTTTGG AAAGATCTAG CACATCTCAC CCAGAGCAGA 4140

GGCCCTGTGG GTGGAGGCTC CTCTCCCTTA GTCACCCTAA TTGAGGAACA TTCTAGCAAA 4200

AGCAAACGCC TCAGTGTTTA ACTGACAGGA GGTTGTCACT CCAATCTGCA AAGGGCTTGC 4260

CTGTGGAACT TCTGCCTCCT GATTCTCACA ACAGCACCTT ACAGCCAAGC CATTCAAAAA 4320

TGCAGAAACA GGCTGGAGGC CTGGGCTCAC TTGCCCAAGG CCAGTCTCTT AGATTGTGCA 4380

GAATTTCTCT TTGATATCAT CAAGGTGTAA TGCTCCATGA TTCACTTCTT TTGAAACCTG 4440

GCATTGAGAC AAGGGACAGG AGGGATCAGA GTTCCTTCAA CTGGGTTGCG TTCCAGTAGC 4500

AAGCATCCCC CAAGGCACAC AGGCCAGCCT CCCTCTGCCC CTGGGAAAGA GACCAGGACA 4560

CCCTCTCCCT TTACCCATGC AGACATGATG CTGGTTCAAT GCTGGCTTCT GAGAAAGACT 4620

CCTATGTGCT CCAGGGCATG CCTGAGGTCC TGGCTGGCAC AGAGCAGGTT GCACATTGCA 4680

ATCCCCTGCT CATCACATTC CCAACACTCA GGTTGCATCC CAGGTATCTT CAGTCAGTAC 4740

CTAGGGGTGG GCGTCAGTAT TTTTCAGGGC CCTCCAGATT CCAGTATGTA GCCAAGGTGG 4800

AGAATCCTAC TTCACAGATT CCTTTCTACC TGGAACCTTT TCATCAGCTT TTGAGGGAGG 4860

GAAAACACTC CTTTGCCGAG GGCAAGCTGA TCAATGACCT GTGTATAGGC AGAGCAGCAA 4920

ACACACGGCT TCAGGGCCAG GCAGGTACAT ACATGGGAAA TGCTGGCTGG GTGAGAGGGA 4980

GCGTGAAGAG CTGTGGGAAG CCGAAGTGGC CCCATCAGAA GCTGTGCACA GGCACCTTGT 5040

TTTTAATGAC ACGGGTAGGT CAAAGCACAA ACAGCTGCCA ACTCATGACC TTTGTCTTAA 5100

AAGTTTAAAC GGCAGGAGAA CTGCTTTGGC TTTTACACAT TTAACATGGT ATCTTGGAGG 5160

CTCCTTAGTG CAGTAGAAAG GACATGAACT TCAAGAGTCA GGAGACACAG GGTCTTGCCT 5220

GAGCACTGCC ATCAGATGGC CCCTTACCCT TCTTGAAATG TAATATGCCA GAGGTCGGCC 5280

CAGATATTCT CTGAGCACCC TTCCAGGCCT AAAACACTAG GATACTGTGA GATTAACTCC 5340

TACTTCTGGT CCTTCACTCC TGCCTGTTGG CAGCTCAGTC AGGTAATAGC ACCTGGAGTT 5400

CACCCACCTG GGTGTCCCCC ACTTCTGCTA ATCTCCTCCT CTTGAATCCT TCTTGCTGTT 5460

CAGCTTGGAA ACTAGAATTT AGGAAGAAAA GTCACTGTAT GATGTAATGC ACAGCTTTGG 5520

CCTTGTTTCT GCACAGTAGT GACCCAAACA TCCCCGATAA AACACCCACT GCTTAAGAGG 5580

CAGGCTCGGA TGGACTATAG CTTTGATACC ACAGCCGAAG ACCCTTGGGT TAGGATTTCT 5640

GACTGCATCA AAAACTTATT TAGCCCCATC ATGAGTGAGA ACCATGGCCA CATGCCTCTA 5700

CAGCCCAATG CCAGCCTGAA TGAAGAAGAA GGGACACAGG GCCACCCAGA TGGGACCCCA 5760

CCAAAGCTGG ACACCGCCAA TGGCACTCCC AAAGTTTACA AGTCAGCAGA CAGCAGCACT 5820

GTGAAGAAAG GTCCTCCTGT GGCTCCCAAG CCAGCCTGGT TTCGCCAAAG CTTGAAAGGT 5880

TTGAGGAATC GTGCTTCAGA CCCAAGAGGG CTCCCTGATC CTGCCTTGTC CACCCAGCCA 5940

GCACCTGCTT CCAGGGAGCA CCTAGGATCA CACATCCGGG CCTCCTCCTC CTCCTCCTCC 6000

ATCAGGCAGA GAATCAGCTC CTTTGAAACC TTTGGCTCCT CTCAACTGCC TGACAAAGGA 6060

GCCCAGAGAC TGAGCCTCCA GCCCTCCTCT GGGGAGGCAG CAAAACCTCT TGGGAAGCAT 6120

GAGGAAGGAC GGTTTTCTGG ACTCTTGGGG CGAGGGGCTG CACCCACTCT TGTGCCCCAG 6180

CAGCCTGAGC AAGTACTGTC CTCGGGGTCC CCTGCAGCCT CCGAGGCCAG AGACCCAGGC 6240

GTGTCTGAGT CCCCTCCCCC AGGGCGGCAG CCCAATCAGA AAACTCTCCC CCCTGGCCCG 6300

GACCCGCTCC TAAGGCTGCT GTCAACACAG GCTGAGGAAT CTCAAGGCCC AGTGCTCAAG 6360

ATGCCTAGCC AGCGAGCACG GAGCTTCCCC CTGACCAGGT CCCAGTCCTG TGAGACGAAG 6420

CTACTTGACG AAAAGACCAG CAAACTCTAT TCTATCAGCA GCCAAGTGTC ATCGGCTGTC 6480

ATGAAATCCT TGCTGTGCCT TCCATCTTCT ATCTCCTGTG CCCAGACTCC CTGCATCCCC 6540

AAGGAAGGGG CATCTCCAAC ATCATCATCC AACGAAGACT CAGCTGCAAA TGGTTCTGCT 6600

GAAACATCTG CCTTGGACAC AGGGTTCTCG CTCAAGTGAG TTTCTACACC CGGTGTTTCT 6660

CTTTACCTTT CTCATCTTTT TCTTTCTCAT CTTTATTTTT AAAAATAATC CTATATATAA 6720

TTTAAAAAAT TCCCAGATAT ATTGATTAAA GAATTGTTCT GCCTCTTTCT TTCCATGTGT 6780

GTGCAGATGT CTGAGTGTGT GTGTGTCTGT CTGTAGGTAT TACACCTCTG CCTTTCACAT 6840

TAAGGAGGAG TTTTCACAAC ATCTGGCTTC AGGAGGGCTG GGAGGTAGGA GGTGGGACTG 6900

GCTCCCTGGT GAATTGCTCA TGAGGGCTGA CATACGCCTG TGGAGATTTG GAAGGTTGAT 6960

GCACATCTGA AATGTCCTGC GGTTACTCAG AAAGACCAGA ATGAGGCCAG GAAATTATCC 7020

ATCAGGAATT CTTACTCTCC AAATGGAATC CACTTGTACT CTGCACGTGG GTTCAACTCC 7080

CTCATCAGGG AGTTAGGATG TCTGGGTCCT AGTCTCAGCT TAGGCACTGA TTCTGACTAT 7140

GAGCAGGTTC TTTCCATGCT CACCCTCAGA TTCCTTGTCA GTTGAAATTA GGAGATGGAT 7200

GAGACCTTCT ATGCAGAACC AAGAGGATGT CAGACGTGCC ATAGGGTCCC TGCTGTAGGG 7260

CTGGGGCTTG GTCTTCCCTC TGATCAAAGT AGCTCTGCAT TTATTAGTTT TATTTATTAT 7320

TCTTACACTG CTGGGAAATA TCTGTAGAGT GAAGGTATGC TAGTATCTAC TCATAGATTT 7380

GTTGCATCAA ATAATATGCA CATAAGTGCT TGGCACCACA CCTGGGACAT AGTAATTATA 7440

CAATCACTGT TACCTCTTTT TAATATTGTT GTTCATACTG TGTGTTGTTT CTCCTTATGA 7500

AAGCCTTTCA GAGCTGAGAG AATATACAGA GGGTCTCACG GAAGCCAAGG AAGACGATGA 7560

TGGGGACCAC AGTTCCCTTC AGTCTGGTCA GTCCGTTATC TCCCTGCTGA GCTCAGAAGA 7620

ATTAAAAAAA CTCATCGAGG AGGTGAAGGT TCTGGATGAA GCAACATTAA AGGTAGGTTT 7680

CCTTTGTAAG CATCTGCAGT AACCAATGGC TTATTATGGC TGTGTGGCCA CCTTAGTTGG 7740

GCCAGAGGGG AAGTAGCTTG AGTAGCCTGC CACATCAGAC CCAGGTTGCG TCCTGTGATG 7800

GTGGGACACT GTAGCACTTG ACCACAGTAA GACCTTCCAT TTGAAGAGAG CCTTTTAGCT 7860

TGTGAACCAC TTTCAGTAGA TTGACTTCTT GCATCTTCTT TTGTCATTTT ATAAATGAGA 7920

AAGGTAAGGC TCAATCAAGG CTACAGAACC TGGGTTTTCT GTCTCCAAGT TCAAGTTCAG 7980

TGCTGTTTCC ACATTCCATG TGCTGCTGTC CTGGCATGTG TCTGTTGTGG GATGCTGTCC 8040

ATTGTAAACA ATGTGGGTTA CAAGAGCTCT CACCTGGAGC TTTCATTATT TCCACTGTGC 8100

ATGGAGAGGT GGCTGATCCC AGGGCTCACA AGTCCCCCAC GCTTCAGTCA AGTCATTCTG 8160

AAAGTCTCAC TTCCCATATG TTTTCTGAGC ATGACCCAAA GGGGTGTGGG GAGGAAGTGG 8220

CCAGGCTGAG CTGGGGCCAG CAGTCAAATG AGCTCAGGCT CATGGGTCCT GCACCCTCTA 8280

GGTGCTGCCC CAGGCCTCCG TAGGCTTTTG GCACTAGAAT GATCCAGGCT AGGATGAAGA 8340

GGATAAGGAG GTTCTCGTTT TCCATACAAG GAGGCCTCAT AGCTGCAATT TCCACATCAA 8400

GAGTGTAGGT GAGTCTGATG AGCCCAAGGT GCTGCTGTGC TGAGATTCTT TCGGCTGTGG 8460

CTTTCACTTG TCACCTGGGA CCATCATCCC CCAGGATCTT ACTCAGTGCA AATGAAATAA 8520

CAGAGGCAGA GCGTGTAAAA CACAAAGAGC CATCCTGCCT GAGCTGCTCT GGGGAGAGTA 8580

TTTGCTTTCT AACATGAGAA GAGCCTTCTA CAAGGCAAGT AACCTGATAC TTGGGTAAAA 8640

GTTGAGAGAG TTGGGCTAGT GTTGGGGCTT GGAGGTGAGG GTGCAGTGAG GTACATTCAT 8700

CCTTCCATGC CTTTGGGTCT TAGGGGCTCC AAGTCTTAGG ATCATAGGGA CAGCTGGAAG 8760

TCAGGTGCTC TAGTGACGCT GAGCAAGTGA ATTCTTTGAC ATAAGTTTAC TCCTTAGTGC 8820

CAAGGTACAA ACAGGTGCCC CAAGAACCTG TAGGTTTACT TTATTTGGTC TGCATGGTGA 8880

TGAAAAAAAT ATTGAATTCT ATACATGATA AAACCTGAAT TGAAACCTGG ACTTTAGGGA 8940

AGTGATCTGG TAGCGCTAGT TCTGTATGCC TACGTAGAGC TGACCCTTTG AGCAGATGTA 9000

CTCGTTGGCG CTCTGCAGTT CCTATCACAC ATCTGCCCAT TTGGCTCATT TTAGGGACCT 9060

GCCTGACTCC TATAGGCATC TGAGTTTGAG ACCCCTGCTC TAGACTGGAA TAGGAGTCTC 9120

TGACTGTGTC CTGGCTCCAT GGGAGTCCCC GTCTAGGCTA GGAAGTACCG TAGTAATGTG 9180

TGTGTGTGTG TGTGTGTGTG TGTGTGTGTC ACACTTGCAC ACTGTGCATT GGGGCAGGAT 9240

GTTAGCTGGG CTTCCTTAGT GCTGCTGCTG TGACCCATGG AGAAGTAGAA GGGAAGAAGG 9300

AGCAACCAAT TCCTGCAGAA CAGCACTGAC CCCTGTTTTG TTTTTTGTTG TTTTTTTTTG 9360

TTTTGTTTTA CCTGAAGTCC TACAACCTGA CTTCATCTCA CACTGTCCAA TATGCTGATT 9420

TCTGGCTGAC TTCATGGCAC TCCCCCTGCC CGGCTGTGGA CAGGGTGAAT GAGAGAGGAA 9480

AATAATTATG CTTGCTGCTT TACATACATT TTTTTTTTCT TCTAAGCTTC CCATGACTCC 9540

TGAAGGTCCA TTCTTTACAG ATGAGGAAAC TGAGGTTTGA GGAGGTGATG TAACTTGGAG 9600

GCTGGCCAAG CTGGGGTTTG AGATAACAAA TCAGTCTGAT GTCAGTCCGA TGTTAAATTG 9660

TTCATCCTCT TGCAGTAAAA TGTTTTTGGA TGTATGTATT TCCTCTGCAG CAATTAGACG 9720

GCATCCATGT CACCATCTTA CACAAGGAGG AAGGTGCTGG TCTTGGGTTC AGCTTGGCAG 9780

GAGGAGCAGA TCTAGAAAAC AAGGTGATTA CGGTGAGTGG CCAAGTGAAG GGGCATGTCA 9840

CAGCCAGAGG CAATGGTTCT GGGGGAGGGG GACACACTTG CCAGGAAGGG GCCCTGTGCT 9900

GGGGAAATGA AGAATGCATG ACACTAGGCC ACTGGGCAGG TCCTGTCCAC TCAGCACATC 9960

CCAGAGCCTG GGGCTGCGTG GAGAGGGTAG CAGGCCTGGC CATGGGCATC TTTTCCTGTG 10020

GGTCCCACTA TTCTGGCTCA TCCAATCTGA TCAGCATTGG CTGCTGCCTT CAGGTCACCT 10080

GTACCTGACC CAGATGGTTT CTGGTTCTGC CAGTTTTGTG GAGCCATGCT GCGGCTGCTC 10140

GCTCTCTAAA GCCGAGTGCA TTGCTGTCAT CCCAGGGCTG TGTTGTCTCA GGGTATCCTT 10200

TGTGTAGGCT GTGCTGGGCT CATTTGAATT TCCATGCCCA ACTGAAAACA AATCCTCCAG 10260

TTCACAGCAT CAGCCAGCAT TCAACATACC ACACCCCCTT GCAGTGGCAA TCTGGCATGT 10320

TCCTGCGTGT CACTTCAGAG TCAATCATGT CAGTGGTGAC TTCCTTGATT TCCTGATAAG 10380

TTTTCTATCA CATAAAAAAC ACTTAAAACC GGTAAGTCTC TATTTCTCTC ACTGAGTGCA 10440

GCTGAGTATT ACAAAAAGAT TCCTGACCGT GTAGTTTACT TTCTACTTGA AGAGGAGGAA 10500

AGAGAGCTTG CCTGTGGGAA TGGCACTTTG GGTATTTTTC TCTGTCCATG AGTAGCAACT 10560

TCTGTCCACG TCATCTGGCC AGTCACCCTT GAGACACTGC AGACAACAGG AAAATAGGAG 10620

GAAGGCGCAC ATGTTGGCTG GGCACATGCA CAAAAGTTCT TTCTCCTTCT GTGTTTGAGC 10680

ATTTCTCTTC CTTTCCAGAT GATTAGAAGG GAACTAACGT AGAGCACCAT CCACGGCCAT 10740

GCTGAGCACT CACTGACCTG TTGTCTAAAT TCATCCTACC CACACTTTGG ATTGATAAAT 10800

TGGTGGCATT TATGCTTCTT TTATAGAGGA GGAACCTGAG GTTCCTCCTT TAATTAACTT 10860

TAATCTTCGT TGGCCTAAAA ATCCTCTAGC ATTGAGGAAC CTGAGGCTCA GAGGAGAGGT 10920

TCCGCTCCAT GCTGGATGTT ACAGCCTGGG GATTCTAACC ATGTAACAGA ATTTTTCTAA 10980

CACCAAAACA ATTTAGAGAA GCAAAGAGCT TTGCTCCTAT CATAAAAGCA AAACTACAGG 11040

TACCACATTT TAGTGGTTTC CATGCATGCT ATCACTCAGT CCTCTTAATT ATAATGGACC 11100

TCATTAAAGA GGCTGAGGCA GAGACATGAG ATATTTTTGT GTGTTTGTTT ATCCCACATA 11160

TCTTGCAGAA AGGGGACCAA GAGGTGACTG GAGGTAAAGA GTCAGAATTT CTAGGGGAGG 11220

AGCTATAAAA ATGTCTAGAC TGCCTAGGAG AGTGTTTCTC AAAATGCATT CTGCCAAATG 11280

AGACCGAGAA TTTCTCTATG AGAAAAGAAT TCTTTGTTGA AACACTTTGG GAATCCCCAT 11340

AATACCCTGC CAACTTAGAA ATCTGCCATG CAGATTTGCA TTGTAGACCC TCTAAATGCC 11400

TTTTGCTTAG AAATCTGCTG CCATGCAAAT TTGCATTGTA GACCCTCTAA TGCCTTTTGC 11460

TTTTTAAAAG TAGACAATGT CAGAGCTTTT GTTTCACCCA GTATTCCTCA AGTTTCTTTG 11520

ATTTTAAAAA ATTTTTCTTG GCCGGGTGTG GTGGCTCATA CCTGTAATTC CAACACTGTG 11580

CGGGGCCAAG GTGAGAGGAT TGCTTGAGCC CAGGAGTTTG AGACCATCCT GGGCAACACT 11640

GGGAGACCTG TCTCTATTTT TTAAAAAATA ATAGGAAAAG CCTTTTTCTT ACACAATACC 11700

CGTTAATATG CCATAGAATC AGTGCCTTGA GAAAACTACT CTGGGGACTT CTGACCTAGG 11760

GCAGGTGAAG CAAAAGATTT TATATGGAAT CCCAACTAGA ATCGTGGTGG TACACTATAG 11820

GACGTTGTGT TGGGATGGAT TCTGAGGGCT TACCTGGTCA TTACTGCTGG TGATCTCTGC 11880

TCTGGATGGA GAAGGAGGGA ATGCTGGCCT CTGTGCCAGC AGCTCCAATC TAGGACACAA 11940

TTATCTTTAA TCTTTGTTGG CCTAAAAATC CTCTAGCATT GACTAACCGG TTCAATCCTC 12000

CTCCAGCAAG TATGTGGACT GGACTTGTGT GATTTCTGGT CCTGACTTCC TTTGGTTTGC 12060

TCAGGTTCAC AGAGTGTTTC CAAATGGGCT GGCCTCCCAG GAAGGGACTA TTCAGAAGGG 12120

CAATGAGGTT CTTTCCATCA ACGGCAAGTC TCTCAAGGGG ACCACGCACC ATGATGCCTT 12180

GGCAATCCTC CGCCAAGCTC GAGAGCCCAG GCAAGCTGTG ATTGTCACAA GGAAGCTGAC 12240

TCCAGAGGCC ATGCCCGACC TCAACTCCTC CACTGACTCT GCAGCCTCAG CCTCTGCAGC 12300

CAGTGATGTT TCTGTAGAAT CTAGTAAGTT CTCCCAACTC AGTGGAAGCC ACATGGGCCA 12360

CATCCTCTTT GGCCATTTGG GGCCAGACCT GATGGGGCTA CTCAGTAATT TGTGACCCCA 12420

AGAATGTGTG GCTGCCTAGT ACACTGCCTG AGACGTGTTT ACATGTGCCT GTGTGCAAAC 12480

ACGGGGGCTG TATCACCCCG GGCTCACTTG AAGCCCAGGG CATCTGTGGC CTGGGGAGAG 12540

GAGAGGATCC CTAACAGAGA CCTTGTGTTT TTCTCAGCAG CAGAGGCCAC AGTCTGCACG 12600

GTGACACTGG AGAAGATGTC GGCAGGGCTG GGCTTCAGCC TGGAAGGAGG GAAGGGCTCC 12660

CTACACGGAG ACAAGCCTCT CACCATTAAC AGGATTTTCA AAGGTGTGGG GTGTGTCTGG 12720

TTCTTTGCGT GCTCTCCAGT TGTGGGCATG TGGCCAGGCC CCCAAAAGGC TTCTGGGCAC 12780

TTTCTGGGCT ATGTTGTTTC CCACAACTCC ATGTCCTCTT CATAGGCATG CTGGTCCTTT 12840

TAGGGCTCAA TTCTGCTTTT TCTACTTTTT CTCCTTTGCT CAGACATCCC CTCAATCCCC 12900

CCTCTGTTTT GATGGGTCTT CAAAAATACC TAAGTCCTGG GCTTGGTTCG GGTTGGCAGG 12960

GCCAGGACTC TAGAGTGGGG CAGTGAGGCA CTGGCCTGTG GGGCAGAATT TTAAAGGGGT 13020

GCCAAAACAC TCAGTAACTC AGATCGATAC TATTTTAATG CAGCGTGTTT TTTAAAATTA 13080

ATTTTAAAAA AACATGTTGG GACAAAATAT CCAAGTTTTA AATCAAGACA GAGTCTGACT 13140

TTGTACTGCA CACTTGGCCT CATTTGCCTT ACCCTAGTCC TGGACACGTC AGCTCCTGCC 13200

TTTATTTAAA ATGTTGATAG ATATTTTGTT CATCAGGGAT TGGAGTACAA ACCAGTCTGA 13260

TATGGGGGTC ACTTGGATTT CCCTGTGAAA ATCATGAATG ACTGTGGCTA CCATGTAAAA 13320

CCATCCCTGA TTCTTTGGTG TTCCTCAAAT TGGAGGTCTC CAAGCCACAG AGCAAGGGGT 13380

TGTAGAGAGA GGAGTACTGG ACAGGGAGGC AGGTGGGCCA GGTTCTAGTC CCAGCTCTGC 13440

CTGTAATGTG CTGAGTGACC CTTCCCTTCT GGGCCTGAGG CTCTTCATCC ATAAAAGGAG 13500

GTAAAGAGGT ACAGGTGTGT GTCTGAGGGC TCTTAGGACT GAGACCCAAA GGGACTCTTA 13560

GCTCTGTCCC TCACCCACTA TGAGCTCCTG CTGCTGACTG GTTTCGTTAG AGGAAGTTCT 13620

GGCTGCGGCT GCAGAAACCC AGAAGGTAGA GTGAGGCTTA CATGGCATTC CCCCCAGAAT 13680

CCATGTTAAC CCCAATTCTG GGAAAGATAT TTCTAATTTT TGAAGGTCAA TTTGGAAGGA 13740

GCATTGGGTT CAATGTCAAG AGGACTAGAT TCCAGTGTTA GTTCTGCCAC ATGACCTTGG 13800

TAGCATGATC TTGGACAAGT CACTTCACCA CCATGGGCCC ATTTGCTTAA ATGTTTAGGA 13860

TGAGACTGCC AGCTGCAGGG TGATGTTGGA AGGAGAGATG CAGATTCTGG AGCCAGAAAG 13920

TCTGGGTTCC AGCCCAGGGC CCACCACTAG CAGCTATGAA GCTCTGGGCC AGTTACTTGA 13980

GTTCTTGGTT TCCTCAGCTG TTAAAAGGAA ACACAAATAA TACACCCCTC ATAGGATTAC 14040

TGTCATAAAT GCAAAACATT AGCACAACGC CTGTTAAAAT AATTGCCCAA TACACTTTAG 14100

CTATATTTTC ATTACTATCA TTAGTATTAT CTTCTACTCT TATCAGGATT TGTGAAGATC 14160

AACTGTGTCA AATGGATGGG AAATTTTATT TTAATATAAA CAGTAAAATA GCATTGTTTT 14220

CACTTGCAGC TTTGAAATAG TGGGGGCCAT ATATGGTTGT TTCCTTTTTT ATGTGGACAC 14280

AGAGGACTTC GTGCCAGAGG CAAGATCCCT GTAAATATTG TTGCACAAAA ATCTCACTAG 14340

CTCTCTTCCC ATACCACCCA ATGCTGATGT CCTCACCACA TGCGGAGAAC AAATGTGAAG 14400

GGAGTAGGAT ATTGGGTCAG TGTCCAAAGC AGGGTCTGGG CAGGACTCAG CTCCCCAGAG 14460

TCCTCTATGA ACTATGGACG GTGCTCCAGG CAGGCTAAGG CGTGGAGCTG CCTGATATTT 14520

CCCTCCCCTG GGGACAGCAA GGGCTATCCC TTTCCAAAGG CCATGGAGAG CTGGAGCCTG 14580

GTGCCCTAAC TTTTGAGTCA CCATCTTAAG AGATGCCTCA TTTTAGAACC ACCAACAAGC 14640

AAGCTCCCAA GGGATGGTGC CCTGTTCTCT ACCAAGCTAT CCTGGCTCTT TGGAGATCAA 14700

GGAGAGGAGG CAACTTTCCT TGTTCCCCAT CATCTGTGGA ACCCATTACC TTCTCCCTCA 14760

TTTCAGGAGC AGCCTCAGAA CAAAGTGAGA CAGTCCAGCC TGGAGATGAA ATCTTGCAGC 14820

TGGGTGGCAC TGCCATGCAG GGCCTCACAC GGTTTGAAGC CTGGAACATC ATCAAGGCAC 14880

TGCCTGATGG ACCTGTCACG ATTGTCATCA GGAGAAAAAG CCTCCAGTCC AAGGAAACCA 14940

CAGCTGCTGG AGACTCCTAG GCAGGACATG CTGAAGCCAA AGCCAATAAC ACACAGCTAA 15000

CACACAGCTC CCATAACCGC TGATTCTCAG GGTCTCTGCT GCCGCCCCAC CCAGATGGGG 15060

GAAAGCACAG GTGGGCTTCC CAGTGGCTGC TGCCCAGGCC CAGACCTTCT AGGACGCCAC 15120

CCAGCAAAAG GTTGTTCCTA AAATAAGGGC AGAGTCACAC GGGGGCAGCT GATACAAATT 15180

GCAGACTGTG TAAAAAGAGA GCTTAATGAT AATATTGTGG TGCCACAAAT AAAATGGATT 15240

TATTAGAATT TCATATGACA TTCATGCCTG GCTTCGCAAA ATGTTTCAAG TACTGTAACT 15300

GTGTCATGAT TCACCCCCAA ACAGTGACAT TTATTTTTCT CATGAATCTG CAATGTGGGC 15360

AGAGATTGGA ATGGGCAGCT CATCTCTGTC CCACTTGGCA TCAGCTGGCG TCATGCAAAG 15420

TCATGCAAAG GCTGGGACCA CGTGAGATCA TTCACTCATA CATCTGGCCG TTGATGTTGG 15480

CTGGGAACTC ACCTGGGGCT GCTGGCCTGA ATGCTTATAG GTGGCCTCTC CTTGTGGCCT 15540

GGCCTCCTCA CAACATGGTG TCTGGATTCC CAGGATGAGC ATCCCAGGAT CGCAAGAGCC 15600

ACGTAGAAGC TGCATCTTGT TTATACCTTT GCCTTGGAAG TTGCATGGCA TCACCTCCAC 15660

CATACTCCAT CAGTTAGAGC TGACACAAAC CTGCCTGGGT TTAAGGGGAG AGGAAATATT 15720

GCTGGGGTCA TTTATGAAAA ATACAGTTTG TCACATGAAA CATTTGCAAA ATTGTTTTTG 15780

GTTGGATTGG AGAAGTAATC CTAGGGAAGG GTGGTGGAGC CAGTAAACAG AGGAGTACAG 15840

GTGAAGCACC AAGCTCAAAG CGTGGACAGG TGTGCCGACA GAAGGAACCA GCGTGTATAT 15900

GAGGGTATCA AATAAAATTG CTACTACTTA CCTACC 15936

CTTTTCGTCA AGTAGCTTCG TCTCACAG 28

GAAATCGAAG CGGCCGCGCT CCGTGCTCGC TGGCTAGGCA TCTTGAG 47

GGTCGACGGC CCGGGCTGGT 20

CCGGACCCGC TCCTAAGGCT GCTGTCAACA CAGGCTGAGG AATCTCAAGG CCCAGTGCTC 60

AAGATGCCTA GCCAGCGAGC ACGGAGCTTC CCCCTGACCA GGTCCCAGTC CTGTGAGACG 120

AAGCTACTTG ACGAAAAGAC CAGCAAACTC TATTCTATCA GCAGCCAAGT GTCATCGGCT 180

GTCATGAAAT CCTTGCTGTG CCTTCCATCT TCTATCTCCT GTGCCCAGAC TCCCTGCATC 240

CCCAAGGAAG GGGCATCTCC AACATCATCA TCCAACGAAG ACTCAGCTGC AAATGGTTCT 300

GCTGAAACAT CTGCCTTGGA CACAGGGTTC TCGCTCAAGT GAGTTTCTAC ACCCGNGGAT 360

GAGACCTTCT ATGCAGAACC AAGAGGATGT CAGACGTGCC ATAGGGTCCC TGCTGTAGGG 420

CTGGGGCTTG GTCTTCCCTC TGATCAAAGT AGCTCTGCAT TTATTAGTTT TATTTATTAT 480

TCTTACACTG CTGGGAAATA TCTGTAGAGT GAAGGTATGC TAGTATCTAC TCATAGATTT 540

GTTGCATCAA ATAATATGCA CATAAGTGCT TGGCACCACA CCTGGGACAT AGTAATTATA 600

CAATCACTGT TACCTCTTTT TAATATTGTT GTTCATACTG TGTGTTGTTT CTCCTTATGA 660

AAGCCTTTCA GAGCTGAGAG AATATACAGA GGGTCTCACG GAAGCCAAGG AAGACGATGA 720

TGGGGACCAC AGTTCCCTTC AGTCTGGTCA GTCCGTTATC TCCCTGCTGA GCTCAGAAGA 780

ATTAAAAAAA CTCATCGAGG AGGTGAAGGT TCTGGATGAA GCAACATTAA AGGTAGGTTT 840

CCTTTGTAAG CATCTGCAGT AACCAATGGC TTATTATGGC TGTGTGGCCA CCTTAGTTGG 900

GCCAGAGGGG AAGTAGCTTG AGTAGCCTGC CACATCAGAC CCAGGTTGCG TCCTGTGATG 960

GTGGGACACT GTAGCACTTG ACCACAGTAA GACCTTCCAT TTGAAGAGAG CCTTTTAGCT 1020

TGTGAACCAC TTTCAGTAGA TTGACTTCTT GCATCTTCTT TTGTCATTTT ATAAATGAGA 1080

AAGGTAAGGC TCAATCAAGG CTACAGAACC TGGGTTTTCT GTCTCCAAGT TCAAGTTCAG 1140

TGCTGTTTCC ACATTCCATG TGCTGCTGTC CTGGCATGTG TCTGTTGTGG GATGCTGTCC 1200

ATTGTAAACA ATGTGGGTTA CAAGAGCTCT CACCTGGAGC TTTCATTATT TCCACTGTGC 1260

ATGGAGAGGT GGCTGATCCC AGGGCTCACA AGTCCCCCAC GCTTCAGTCA AGTCATTCTG 1320

AAAGTCTCAC TTCCCATATG TTTTCTGAGC ATGACCCAAA GGGGTGTGGG GAGGAAGTGG 1380

CCAGGCTGAG CTGGGGCCAG CAGTCAAATG AGCTCAGGCT CATGGGTCCT GCACCCTCTA 1440

GGTGCTGCCC CAGGCCTCCG TAGGCTTTTG GCACTAGAAT GATCCAGGCT AGGATGAAGA 1500

GGATAAGGAG GTTCTCGTTT TCCATACAAG GAGGCCTCAT AGCTGCAATT TCCACATCAA 1560

GAGTGTAGGT GAGTCTGATG AGCCCAAGGT GCTGCTGTGC TGAGATTCTT TCGGCTGTGG 1620

CTTTCACTTG TCACCTGGGA CCATCATCCC CCAGGATCTT ACTCAGTGCA AATGAAATAA 1680

CAGAGGCAGA GCGTGTAAAA CACAAAGAGC CATCCTGCCT GAGCTGCTCT GGGGAGAGTA 1740

TTTGCTTTCT AACATGAGAA GAGCCTTCTA CAAGGCAAGT AACCTGATAC TTGGGTAAAA 1800

GTTGAGAGAG TTGGGCTAGT GTTGGGGCTT GGAGGTGAGG GTGCAGTGAG GTACATTCAT 1860

CCTTCCATGC CTTTGGGTCT TAGGGGCTCC AAGTCTTAGG ATCATAGGGA CAGCTGGAAG 1920

TCAGGTGCTC TAGTGACGCT GAGCAAGTGA ATTCTTTGAC ATAAGTTTAC TCCTTAGTGC 1980

CAAGGTACAA ACAGGTGCCC CAAGAACCTG TAGGTTTACT TTATTTGGTC TGCATGGTGA 2040

TGAAAAAAAT ATTGAATTCT ATACATGATA AAACCTGAAT TGAAACCTGG ACTTTAGGGA 2100

AGTGATCTGG TAGCGCTAGT TCTGTATGCC TACGTAGAGC TGACCCTTTG AGCAGATGTA 2160

CTCGTTGGCG CTCTGCAGTT CCTATCACAC ATCTGCCCAT TTGGCTCATT TTAGGGACCT 2220

GCCTGACTCC TATAGGCATC TGAGTTTGAG ACCCCTGCTC TAGACTGGAA TAGGAGTCTC 2280

TGACTGTGTC CTGGCTCCAT GGGAGTCCCC GTCTAGGCTA GGAAGTACCG TAGTAATGTG 2340

TGTGTGTGTG TGTGTGTGTG TGTGTGTGTC ACACTTGCAC ACTGTGCATT GGGGCAGGAT 2400

GTTAGCTGGG CTTCCTTAGT GCTGCTGCTG TGACCCATGG AGAAGTAGAA GGGAAGAAGG 2460

AGCAACCAAT TCCTGCAGAA CAGCACTGAC CCCTGTTTTG TTTTTTGTTG TTTTTTTTTG 2520

TTTTGTTTTA CCTGAAGTCC TACAACCTGA CTTCATCTCA CACTGTCCAA TATGCTGATT 2580

TCTGGCTGAC TTCATGGCAC TCCCCCTGCC CGGCTGTGGA CAGGGTGAAT GAGAGAGGAA 2640

AATAATTATG CTTGCTGCTT TACATACATT TTTTTTTTCT TCTAAGCTTC CCATGACTCC 2700

TGAAGGTCCA TTCTTTACAG ATGAGGAAAC TGAGGTTTGA GGAGGTGATG TAACTTGGAG 2760

GCTGGCCAAG CTGGGGTTTG AGATAACAAA TCAGTCTGAT GTCAGTCCGA TGTTAAATTG 2820

TTCATCCTCT TGCAGTAAAA TGTTTTTGGA TGTATGTATT TCCTCTGCAG CAATTAGACG 2880

GCATCCATGT CACCATCTTA CACAAGGAGG AAGGTGCTGG TCTTGGGTTC AGCTTGGCAG 2940

GAGGAGCAGA TCTAGAAAAC AAGGTGATTA CGGTGAGTGG CCAAGTGAAG GGGCATGTCA 3000

CAGCCAGAGG CAATGGTTCT GGGGGAGGGG GACACACTTG CCAGGAAGGG GCCCTGTGCT 3060

GGGGAAATGA AGAATGCATG ACACTAGGCC ACTGGGCAGG TCCTGTCCAC TCAGCACATC 3120

CCAGAGCCTG GGGCTGCGTG GAGAGGGTAG CAGGCCTGGC CATGGGCATC TTTTCCTGTG 3180

GGTCCCACTA TTCTGGCTCA TCCAATCTGA TCAGCATTGG CTGCTGCCTT CAGGTCACCT 3240

GTACCTGACC CAGATGGTTT CTGGTTCTGC CAGTTTTGTG GAGCCATGCT GCGGCTGCTC 3300

GCTCTCTAAA GCCGAGTGCA TTGCTGTCAT CCCAGGGCTG TGTTGTCTCA GGGTATCCTT 3360

TGTGTAGGCT GTGCTGGGCT CATTTGAATT TCCATGCCCA ACTGAAAACA AATCCTCCAG 3420

TTCACAGCAT CAGCCAGCAT TCAACATACC ACACCCCCTT GCAGTGGCAA TCTGGCATGT 3480

TCCTGCGTGT CACTTCAGAG TCAATCATGT CAGTGGTGAC TTCCTTGATT TCCTGATAAG 3540

TTTTCTATCA CATAAAAAAC ACTTAAAACC GGTAAGTCTC TATTTCTCTC ACTGAGTGCA 3600

GCTGAGTATT ACAAAAAGAT TCCTGACCGT GTAGTTTACT TTCTACTTGA AGAGGAGGAA 3660

AGAGAGCTTG CCTGTGGGAA TGGCACTTTG GGTATTTTTC TCTGTCCATG AGTAGCAACT 3720

TCTGTCCACG TCATCTGGCC AGTCACCCTT GAGACACTGC AGACAACAGG AAAATAGGAG 3780

GAAGGCGCAC ATGTTGGCTG GGCACATGCA CAAAAGTTCT TTCTCCTTCT GTGTTTGAGC 3840

ATTTCTCTTC CTTTCCAGAT GATTAGAAGG GAACTAACGT AGAGCACCAT CCACGGCCAT 3900

GCTGAGCACT CACTGACCTG TTGTCTAAAT TCATCCTACC CACACTTTGG ATTGATAAAT 3960

TGGTGGCATT TATGCTTCTT TTATAGAGGA GGAACCTGAG GTTCCTCCTT TAATTAACTT 4020

TAATCTTCGT TGGCCTAAAA ATCCTCTAGC ATTGAGGAAC CTGAGGCTCA GAGGAGAGGT 4080

TCCGCTCCAT GCTGGATGTT ACAGCCTGGG GATTCTAACC ATGTAACAGA ATTTTTCTAA 4140

CACCAAAACA ATTTAGAGAA GCAAAGAGCT TTGCTCCTAT CATAAAAGCA AAACTACAGG 4200

TACCACATTT TAGTGGTTTC CATGCATGCT ATCACTCAGT CCTCTTAATT ATAATGGACC 4260

TCATTAAAGA GGCTGAGGCA GAGACATGAG ATATTTTTGT GTGTTTGTTT ATCCCACATA 4320

TCTTGCAGAA AGGGGACCAA GAGGTGACTG GAGGTAAAGA GTCAGAATTT CTAGGGGAGG 4380

AGCTATAAAA ATGTCTAGAC TGCCTAGGAG AGTGTTTCTC AAAATGCATT CTGCCAAATG 4440

AGACCGAGAA TTTCTCTATG AGAAAAGAAT TCTTTGTTGA AACACTTTGG GAATCCCCAT 4500

AATACCCTGC CAACTTAGAA ATCTGCCATG CAGATTTGCA TTGTAGACCC TCTAAATGCC 4560

TTTTGCTTAG AAATCTGCTG CCATGCAAAT TTGCATTGTA GACCCTCTAA TGCCTTTTGC 4620

TTTTTAAAAG TAGACAATGT CAGAGCTTTT GTTTCACCCA GTATTCCTCA AGTTTCTTTG 4680

ATTTTAAAAA ATTTTTCTTG GCCGGGTGTG GTGGCTCATA CCTGTAATTC CAACACTGTG 4740

CGGGGCCAAG GTGAGAGGAT TGCTTGAGCC CAGGAGTTTG AGACCATCCT GGGCAACACT 4800

GGGAGACCTG TCTCTATTTT TTAAAAAATA ATAGGAAAAG CCTTTTTCTT ACACAATACC 4860

CGTTAATATG CCATAGAATC AGTGCCTTGA GAAAACTACT CTGGGGACTT CTGACCTAGG 4920

GCAGGTGAAG CAAAAGATTT TATATGGAAT CCCAACTAGA ATCGTGGTGG TACACTATAG 4980

GACGTTGTGT TGGGATGGAT TCTGAGGGCT TACCTGGTCA TTACTGCTGG TGATCTCTGC 5040

TCTGGATGGA GAAGGAGGGA ATGCTGGCCT CTGTGCCAGC AGCTCCAATC TAGGACACAA 5100

TTATCTTTAA TCTTTGTTGG CCTAAAAATC CTCTAGCATT GACTAACCGG TTCAATCCTC 5160

CTCCAGCAAG TATGTGGACT GGACTTGTGT GATTTCTGGT CCTGACTTCC TTTGGTTTGC 5220

TCAGGTTCAC AGAGTGTTTC CAAATGGGCT GGCCTCCCAG GAAGGGACTA TTCAGAAGGG 5280

CAATGAGGTT CTTTCCATCA ACGGCAAGTC TCTCAAGGGG ACCACGCACC ATGATGCCTT 5340

GGCAATCCTC CGCCAAGCTC GAGAGCCCAG GCAAGCTGTG ATTGTCACAA GGAAGCTGAC 5400

TCCAGAGGCC ATGCCCGACC TCAACTCCTC CACTGACTCT GCAGCCTCAG CCTCTGCAGC 5460

CAGTGATGTT TCTGTAGAAT CTAGTAAGTT CTCCCAACTC AGTGGAAGCC ACATGGGCCA 5520

CATCCTCTTT GGCCATTTGG GGCCAGACCT GATGGGGCTA CTCAGTAATT TGTGACCCCA 5580

AGAATGTGTG GCTGCCTAGT ACACTGCCTG AGACGTGTTT ACATGTGCCT GTGTGCAAAC 5640

ACGGGGGCTG TATCACCCCG GGCTCACTTG AAGCCCAGGG CATCTGTGGC CTGGGGAGAG 5700

GAGAGGATCC CTAACAGAGA CCTTGTGTTT TTCTCAGCAG CAGAGGCCAC AGTCTGCACG 5760

GTGACACTGG AGAAGATGTC GGCAGGGCTG GGCTTCAGCC TGGAAGGAGG GAAGGGCTCC 5820

CTACACGGAG ACAAGCCTCT CACCATTAAC AGGATTTTCA AAGGTGTGGG GTGTGTCTGG 5880

TTCTTTGCGT GCTCTCCAGT TGTGGGCATG TGGCCAGGCC CCCAAAAGGC TTCTGGGCAC 5940

TTTCTGGGCT ATGTTGTTTC CCACAACTCC ATGTCCTCTT CATAGGCATG CTGGTCCTTT 6000

TAGGGCTCAA TTCTGCTTTT TCTACTTTTT CTCCTTTGCT CAGACATCCC CTCAATCCCC 6060

CCTCTGTTTT GATGGGTCTT CAAAAATACC TAAGTCCTGG GCTTGGTTCG GGTTGGCAGG 6120

GCCAGGACTC TAGAGTGGGG CAGTGAGGCA CTGGCCTGTG GGGCAGAATT TTAAAGGGGT 6180

GCCAAAACAC TCAGTAACTC AGATCGATAC TATTTTAATG CAGCGTGTTT TTTAAAATTA 6240

ATTTTAAAAA AACATGTTGG GACAAAATAT CCAAGTTTTA AATCAAGACA GAGTCTGACT 6300

TTGTACTGCA CACTTGGCCT CATTTGCCTT ACCCTAGTCC TGGACACGTC AGCTCCTGCC 6360

TTTATTTAAA ATGTTGATAG ATATTTTGTT CATCAGGGAT TGGAGTACAA ACCAGTCTGA 6420

TATGGGGGTC ACTTGGATTT CCCTGTGAAA ATCATGAATG ACTGTGGCTA CCATGTAAAA 6480

CCATCCCTGA TTCTTTGGTG TTCCTCAAAT TGGAGGTCTC CAAGCCACAG AGCAAGGGGT 6540

TGTAGAGAGA GGAGTACTGG ACAGGGAGGC AGGTGGGCCA GGTTCTAGTC CCAGCTCTGC 6600

CTGTAATGTG CTGAGTGACC CTTCCCTTCT GGGCCTGAGG CTCTTCATCC ATAAAAGGAG 6660

GTAAAGAGGT ACAGGTGTGT GTCTGAGGGC TCTTAGGACT GAGACCCAAA GGGACTCTTA 6720

GCTCTGTCCC TCACCCACTA TGAGCTCCTG CTGCTGACTG GTTTCGTTAG AGGAAGTTCT 6780

GGCTGCGGCT GCAGAAACCC AGAAGGTAGA GTGAGGCTTA CATGGCATTC CCCCCAGAAT 6840

CCATGTTAAC CCCAATTCTG GGAAAGATAT TTCTAATTTT TGAAGGTCAA TTTGGAAGGA 6900

GCATTGGGTT CAATGTCAAG AGGACTAGAT TCCAGTGTTA GTTCTGCCAC ATGACCTTGG 6960

TAGCATGATC TTGGACAAGT CACTTCACCA CCATGGGCCC ATTTGCTTAA ATGTTTAGGA 7020

TGAGACTGCC AGCTGCAGGG TGATGTTGGA AGGAGAGATG CAGATTCTGG AGCCAGAAAG 7080

TCTGGGTTCC AGCCCAGGGC CCACCACTAG CAGCTATGAA GCTCTGGGCC AGTTACTTGA 7140

GTTCTTGGTT TCCTCAGCTG TTAAAAGGAA ACACAAATAA TACACCCCTC ATAGGATTAC 7200

TGTCATAAAT GCAAAACATT AGCACAACGC CTGTTAAAAT AATTGCCCAA TACACTTTAG 7260

CTATATTTTC ATTACTATCA TTAGTATTAT CTTCTACTCT TATCAGGATT TGTGAAGATC 7320

AACTGTGTCA AATGGATGGG AAATTTTATT TTAATATAAA CAGTAAAATA GCATTGTTTT 7380

CACTTGCAGC TTTGAAATAG TGGGGGCCAT ATATGGTTGT TTCCTTTTTT ATGTGGACAC 7440

AGAGGACTTC GTGCCAGAGG CAAGATCCCT GTAAATATTG TTGCACAAAA ATCTCACTAG 7500

CTCTCTTCCC ATACCACCCA ATGCTGATGT CCTCACCACA TGCGGAGAAC AAATGTGAAG 7560

GGAGTAGGAT ATTGGGTCAG TGTCCAAAGC AGGGTCTGGG CAGGACTCAG CTCCCCAGAG 7620

TCCTCTATGA ACTATGGACG GTGCTCCAGG CAGGCTAAGG CGTGGAGCTG CCTGATATTT 7680

CCCTCCCCTG GGGACAGCAA GGGCTATCCC TTTCCAAAGG CCATGGAGAG CTGGAGCCTG 7740

GTGCCCTAAC TTTTGAGTCA CCATCTTAAG AGATGCCTCA TTTTAGAACC ACCAACAAGC 7800

AAGCTCCCAA GGGATGGTGC CCTGTTCTCT ACCAAGCTAT CCTGGCTCTT TGGAGATCAA 7860

GGAGAGGAGG CAACTTTCCT TGTTCCCCAT CATCTGTGGA ACCCATTACC TTCTCCCTCA 7920

TTTCAGGAGC AGCCTCAGAA CAAAGTGAGA CAGTCCAGCC TGGAGATGAA ATCTTGCAGC 7980

TGGGTGGCAC TGCCATGCAG GGCCTCACAC GGTTTGAAGC CTGGAACATC ATCAAGGCAC 8040

TGCCTGATGG ACCTGTCACG ATTGTCATCA GGAGAAAAAG CCTCCAGTCC AAGGAAACCA 8100

CAGCTGCTGG AGACTCCTAG GCAGGACATG CTGAAGCCAA AGCCAATAAC ACACAGCTAA 8160

CACACAGCTC CCATAACCGC TGATTCTCAG GGTCTCTGCT GCCGCCCCAC CCAGATGGGG 8220

GAAAGCACAG GTGGGCTTCC CAGTGGCTGC TGCCCAGGCC CAGACCTTCT AGGACGCCAC 8280

CCAGCAAAAG GTTGTTCCTA AAATAAGGGC AGAGTCACAC GGGGGCAGCT GATACAAATT 8340

GCAGACTGTG TAAAAAGAGA GCTTAATGAT AATATTGTGG TGCCACAAAT AAAATGGATT 8400

TATTAGAATT TCATATGACA TTCATGCCTG GCTTCGCAAA ATGTTTCAAG TACTGTAACT 8460

GTGTCATGAT TCACCCCCAA ACAGTGACAT TTATTTTTCT CATGAATCTG CAATGTGGGC 8520

AGAGATTGGA ATGGGCAGCT CATCTCTGTC CCACTTGGCA TCAGCTGGCG TCATGCAAAG 8580

TCATGCAAAG GCTGGGACCA CGTGAGATCA TTCACTCATA CATCTGGCCG TTGATGTTGG 8640

CTGGGAACTC ACCTGGGGCT GCTGGCCTGA ATGCTTATAG GTGGCCTCTC CTTGTGGCCT 8700

GGCCTCCTCA CAACATGGTG TCTGGATTCC CAGGATGAGC ATCCCAGGAT CGCAAGAGCC 8760

ACGTAGAAGC TGCATCTTGT TTATACCTTT GCCTTGGAAG TTGCATGGCA TCACCTCCAC 8820

CATACTCCAT CAGTTAGAGC TGACACAAAC CTGCCTGGGT TTAAGGGGAG AGGAAATATT 8880

GCTGGGGTCA TTTATGAAAA ATACAGTTTG TCACATGAAA CATTTGCAAA ATTGTTTTTG 8940

GTTGGATTGG AGAAGTAATC CTAGGGAAGG GTGGTGGAGC CAGTAAACAG AGGAGTACAG 9000

GTGAAGCACC AAGCTCAAAG CGTGGACAGG TGTGCCGACA GAAGGAACCA GCGTGTATAT 9060

GAGGGTATCA AATAAAATTG CTACTACTTA CCTACC 9096

CTGCTGCCAC TGCTGCTACC ACAGGAAGAC ACAGCAGGGA GAAGCCCTAG TGCCTCTGCC 60

GGCTGCCCAG GACCTGGTAT CGGCCCACAG ACCAAGTCCT CCACAGAGGG CGAGCCAGGG 120

TGGAGAAGAG CCAGCCCAGT GACCCAAACA TCCCCGATAA AACACCCACT GCTTAAGAGG 180

CAGGCTCGG ATG GAC TAT AGC TTT GAT ACC ACA GCC GAA GAC CCT TGG 228

Met Asp Tyr Ser Phe Asp Thr Thr Ala Glu Asp Pro Trp

1 5 10

GTT AGG ATT TCT GAC TGC ATC AAA AAC TTA TTT AGC CCC ATC ATG AGT 276

Val Arg Ile Ser Asp Cys Ile Lys Asn Leu Phe Ser Pro Ile Met Ser

15 20 25

GAG AAC CAT GGC CAC ATG CCT CTA CAG CCC AAT GCC AGC CTG AAT GAA 324

Glu Asn His Gly His Met Pro Leu Gln Pro Asn Ala Ser Leu Asn Glu

30 35 40 45

GAA GAA GGG ACA CAG GGC CAC CCA GAT GGG ACC CCA CCA AAG CTG GAC 372

Glu Glu Gly Thr Gln Gly His Pro Asp Gly Thr Pro Pro Lys Leu Asp

50 55 60

ACC GCC AAT GGC ACT CCC AAA GTT TAC AAG TCA GCA GAC AGC AGC ACT 420

Thr Ala Asn Gly Thr Pro Lys Val Tyr Lys Ser Ala Asp Ser Ser Thr

65 70 75

GTG AAG AAA GGT CCT CCT GTG GCT CCC AAG CCA GCC TGG TTT CGC CAA 468

Val Lys Lys Gly Pro Pro Val Ala Pro Lys Pro Ala Trp Phe Arg Gln

80 85 90

AGC TTG AAA GGT TTG AGG AAT CGT GCT TCA GAC CCA AGA GGG CTC CCT 516

Ser Leu Lys Gly Leu Arg Asn Arg Ala Ser Asp Pro Arg Gly Leu Pro

95 100 105

GAT CCT GCC TTG TCC ACC CAG CCA GCA CCT GCT TCC AGG GAG CAC CTA 564

Asp Pro Ala Leu Ser Thr Gln Pro Ala Pro Ala Ser Arg Glu His Leu

110 115 120 125

GGA TCA CAC ATC CGG GCC TCC TCC TCC TCC TCC TCC ATC AGG CAG AGA 612

Gly Ser His Ile Arg Ala Ser Ser Ser Ser Ser Ser Ile Arg Gln Arg

130 135 140

ATC AGC TCC TTT GAA ACC TTT GGC TCC TCT CAA CTG CCT GAC AAA GGA 660

Ile Ser Ser Phe Glu Thr Phe Gly Ser Ser Gln Leu Pro Asp Lys Gly

145 150 155

GCC CAG AGA CTG AGC CTC CAG CCC TCC TCT GGG GAG GCA GCA AAA CCT 708

Ala Gln Arg Leu Ser Leu Gln Pro Ser Ser Gly Glu Ala Ala Lys Pro

160 165 170

CTT GGG AAG CAT GAG GAA GGA CGG TTT TCT GGA CTC TTG GGG CGA GGG 756

Leu Gly Lys His Glu Glu Gly Arg Phe Ser Gly Leu Leu Gly Arg Gly

175 180 185

GCT GCA CCC ACT CTT GTG CCC CAG CAG CCT GAG CAA GTA CTG TCC TCG 804

Ala Ala Pro Thr Leu Val Pro Gln Gln Pro Glu Gln Val Leu Ser Ser

190 195 200 205

GGG TCC CCT GCA GCC TCC GAG GCC AGA GAC CCA GGC GTG TCT GAG TCC 852

Gly Ser Pro Ala Ala Ser Glu Ala Arg Asp Pro Gly Val Ser Glu Ser

210 215 220

CCT CCC CCA GGG CGG CAG CCC AAT CAG AAA ACT CTC CCC CCT GGC CCG 900

Pro Pro Pro Gly Arg Gln Pro Asn Gln Lys Thr Leu Pro Pro Gly Pro

225 230 235

GAC CCG CTC CTA AGG CTG CTG TCA ACA CAG GCT GAG GAA TCT CAA GGC 948

Asp Pro Leu Leu Arg Leu Leu Ser Thr Gln Ala Glu Glu Ser Gln Gly

240 245 250

CCA GTG CTC AAG ATG CCT AGC CAG CGA GCA CGG AGC TTC CCC CTG ACC 996

Pro Val Leu Lys Met Pro Ser Gln Arg Ala Arg Ser Phe Pro Leu Thr

255 260 265

AGG TCC CAG TCC TGT GAG ACG AAG CTA CTT GAC GAA AAG ACC AGC AAA 1044

Arg Ser Gln Ser Cys Glu Thr Lys Leu Leu Asp Glu Lys Thr Ser Lys

270 275 280 285

CTC TAT TCT ATC AGC AGC CAA GTG TCA TCG GCT GTC ATG AAA TCC TTG 1092

Leu Tyr Ser Ile Ser Ser Gln Val Ser Ser Ala Val Met Lys Ser Leu

290 295 300

CTG TGC CTT CCA TCT TCT ATC TCC TGT GCC CAG ACT CCC TGC ATC CCC 1140

Leu Cys Leu Pro Ser Ser Ile Ser Cys Ala Gln Thr Pro Cys Ile Pro

305 310 315

AAG GAA GGG GCA TCT CCA ACA TCA TCA TCC AAC GAA GAC TCA GCT GCA 1188

Lys Glu Gly Ala Ser Pro Thr Ser Ser Ser Asn Glu Asp Ser Ala Ala

320 325 330

AAT GGT TCT GCT GAA ACA TCT GCC TTG GAC ACA GGG TTC TCG CTC AAC 1236

Asn Gly Ser Ala Glu Thr Ser Ala Leu Asp Thr Gly Phe Ser Leu Asn

335 340 345

CTT TCA GAG CTG AGA GAA TAT ACA GAG GGT CTC ACG GAA GCC AAG GAA 1284

Leu Ser Glu Leu Arg Glu Tyr Thr Glu Gly Leu Thr Glu Ala Lys Glu

350 355 360 365

GAC GAT GAT GGG GAC CAC AGT TCC CTT CAG TCT GGT CAG TCC GTT ATC 1332

Asp Asp Asp Gly Asp His Ser Ser Leu Gln Ser Gly Gln Ser Val Ile

370 375 380

TCC CTG CTG AGC TCA GAA GAA TTA AAA AAA CTC ATC GAG GAG GTG AAG 1380

Ser Leu Leu Ser Ser Glu Glu Leu Lys Lys Leu Ile Glu Glu Val Lys

385 390 395

GTT CTG GAT GAA GCA ACA TTA AAG CAA TTA GAC GGC ATC CAT GTC ACC 1428

Val Leu Asp Glu Ala Thr Leu Lys Gln Leu Asp Gly Ile His Val Thr

400 405 410

ATC TTA CAC AAG GAG GAA GGT GCT GGT CTT GGG TTC AGC TTG GCA GGA 1476

Ile Leu His Lys Glu Glu Gly Ala Gly Leu Gly Phe Ser Leu Ala Gly

415 420 425

GGA GCA GAT CTA GAA AAC AAG GTG ATT ACG GTT CAC AGA GTG TTT CCA 1524

Gly Ala Asp Leu Glu Asn Lys Val Ile Thr Val His Arg Val Phe Pro

430 435 440 445

AAT GGG CTG GCC TCC CAG GAA GGG ACT ATT CAG AAG GGC AAT GAG GTT 1572

Asn Gly Leu Ala Ser Gln Glu Gly Thr Ile Gln Lys Gly Asn Glu Val

450 455 460

CTT TCC ATC AAC GGC AAG TCT CTC AAG GGG ACC ACG CAC CAT GAT GCC 1620

Leu Ser Ile Asn Gly Lys Ser Leu Lys Gly Thr Thr His His Asp Ala

465 470 475

TTG GCA ATC CTC CGC CAA GCT CGA GAG CCC AGG CAA GCT GTG ATT GTC 1668

Leu Ala Ile Leu Arg Gln Ala Arg Glu Pro Arg Gln Ala Val Ile Val

480 485 490

ACA AGG AAG CTG ACT CCA GAG GCC ATG CCC GAC CTC AAC TCC TCC ACT 1716

Thr Arg Lys Leu Thr Pro Glu Ala Met Pro Asp Leu Asn Ser Ser Thr

495 500 505

GAC TCT GCA GCC TCA GCC TCT GCA GCC AGT GAT GTT TCT GTA GAA TCT 1764

Asp Ser Ala Ala Ser Ala Ser Ala Ala Ser Asp Val Ser Val Glu Ser

510 515 520 525

ACA GCA GAG GCC ACA GTC TGC ACG GTG ACA CTG GAG AAG ATG TCG GCA 1812

Thr Ala Glu Ala Thr Val Cys Thr Val Thr Leu Glu Lys Met Ser Ala

530 535 540

GGG CTG GGC TTC AGC CTG GAA GGA GGG AAG GGC TCC CTA CAC GGA GAC 1860

Gly Leu Gly Phe Ser Leu Glu Gly Gly Lys Gly Ser Leu His Gly Asp

545 550 555

AAG CCT CTC ACC ATT AAC AGG ATT TTC AAA GGA GCA GCC TCA GAA CAA 1908

Lys Pro Leu Thr Ile Asn Arg Ile Phe Lys Gly Ala Ala Ser Glu Gln

560 565 570

AGT GAG ACA GTC CAG CCT GGA GAT GAA ATC TTG CAG CTG GGT GGC ACT 1956

Ser Glu Thr Val Gln Pro Gly Asp Glu Ile Leu Gln Leu Gly Gly Thr

575 580 585

GCC ATG CAG GGC CTC ACA CGG TTT GAA GCC TGG AAC ATC ATC AAG GCA 2004

Ala Met Gln Gly Leu Thr Arg Phe Glu Ala Trp Asn Ile Ile Lys Ala

590 595 600 605

CTG CCT GAT GGA CCT GTC ACG ATT GTC ATC AGG AGA AAA AGC CTC CAG 2052

Leu Pro Asp Gly Pro Val Thr Ile Val Ile Arg Arg Lys Ser Leu Gln

610 615 620

TCC AAG GAA ACC ACA GCT GCT GGA GAC TCC TAG GCAGGACATG CTGAAGCCAA 2105

Ser Lys Glu Thr Thr Ala Ala Gly Asp Ser *

625 630

AGCCAATAAC ACACAGCTAA CACACAGCTC CCATAACCGC TGATTCTCAG GGTCTCTGCT 2165

GCCGCCCCAC CCAGATGGGG GAAAGCACAG GTGGGCTTCC CAGTGGCTGC TGCCCAGGCC 2225

CAGACCTTCT AGGACGCCAC CCAGCAAAAG GTTGTTCCTA AAATAAGGGC AGAGTCACAC 2285

GGGGGCAGCT GATACAAATT GCAGACTGTG TAAAAAGAGA GCTTAATGAT AATATTGTGG 2345

TGCCACAAAT AAAATGGATT TATTAGAATT TCATATGACA TTCATGCCTG GCTTCGCAAA 2405

ATGTTTCAAG TACTGTAACT GTGTCATGAT TCACCCCCAA ACAGTGACAT TTATTTTTCT 2465

CATGAATCTG CAATGTGGGC AGAGATTGGA ATGGGCAGCT CATCTCTGTC CCACTTGGCA 2525

TCAGCTGGCG TCATGCAAAG TCATGCAAAG GCTGGGACCA CGTGAGATCA TTCACTCATA 2585

CATCTGGCCG TTGATGTTGG CTGGGAACTC ACCTGGGGCT GCTGGCCTGA ATGCTTATAG 2645

GTGGCCTCTC CTTGTGGCCT GGCCTCCTCA CAACATGGTG TCTGGATTCC CAGGATGAGC 2705

ATCCCAGGAT CGCAAGAGCC ACGTAGAAGC TGCATCTTGT TTATACCTTT GCCTTGGAAG 2765

TTGCATGGCA TCACCTCCAC CATACTCCAT CAGTTAGAGC TGACACAAAC CTGCCTGGGT 2825

TTAAGGGGAG AGGAAATATT GCTGGGGTCA TTTATGAAAA ATACAGTTTG TCACATGAAA 2885

CATTTGCAAA ATTGTTTTTG GTTGGATTGG AGAAGTAATC CTAGGGAAGG GTGGTGGAGC 2945

CAGTAAACAG AGGAGTACAG GTGAAGCACC AAGCTCAAAG CGTGGACAGG TGTGCCGACA 3005

GAAGGAACCA GCGTGTATAT GAGGGTATCA AATAAAATTG CTACTACTTA CCTACC 3061

631 amino acids

amino acid

linear

protein

7

Met Asp Tyr Ser Phe Asp Thr Thr Ala Glu Asp Pro Trp Val Arg Ile

1 5 10 15

Ser Asp Cys Ile Lys Asn Leu Phe Ser Pro Ile Met Ser Glu Asn His

20 25 30

Gly His Met Pro Leu Gln Pro Asn Ala Ser Leu Asn Glu Glu Glu Gly

35 40 45

Thr Gln Gly His Pro Asp Gly Thr Pro Pro Lys Leu Asp Thr Ala Asn

50 55 60

Gly Thr Pro Lys Val Tyr Lys Ser Ala Asp Ser Ser Thr Val Lys Lys

65 70 75 80

Gly Pro Pro Val Ala Pro Lys Pro Ala Trp Phe Arg Gln Ser Leu Lys

85 90 95

Gly Leu Arg Asn Arg Ala Ser Asp Pro Arg Gly Leu Pro Asp Pro Ala

100 105 110

Leu Ser Thr Gln Pro Ala Pro Ala Ser Arg Glu His Leu Gly Ser His

115 120 125

Ile Arg Ala Ser Ser Ser Ser Ser Ser Ile Arg Gln Arg Ile Ser Ser

130 135 140

Phe Glu Thr Phe Gly Ser Ser Gln Leu Pro Asp Lys Gly Ala Gln Arg

145 150 155 160

Leu Ser Leu Gln Pro Ser Ser Gly Glu Ala Ala Lys Pro Leu Gly Lys

165 170 175

His Glu Glu Gly Arg Phe Ser Gly Leu Leu Gly Arg Gly Ala Ala Pro

180 185 190

Thr Leu Val Pro Gln Gln Pro Glu Gln Val Leu Ser Ser Gly Ser Pro

195 200 205

Ala Ala Ser Glu Ala Arg Asp Pro Gly Val Ser Glu Ser Pro Pro Pro

210 215 220

Gly Arg Gln Pro Asn Gln Lys Thr Leu Pro Pro Gly Pro Asp Pro Leu

225 230 235 240

Leu Arg Leu Leu Ser Thr Gln Ala Glu Glu Ser Gln Gly Pro Val Leu

245 250 255

Lys Met Pro Ser Gln Arg Ala Arg Ser Phe Pro Leu Thr Arg Ser Gln

260 265 270

Ser Cys Glu Thr Lys Leu Leu Asp Glu Lys Thr Ser Lys Leu Tyr Ser

275 280 285

Ile Ser Ser Gln Val Ser Ser Ala Val Met Lys Ser Leu Leu Cys Leu

290 295 300

Pro Ser Ser Ile Ser Cys Ala Gln Thr Pro Cys Ile Pro Lys Glu Gly

305 310 315 320

Ala Ser Pro Thr Ser Ser Ser Asn Glu Asp Ser Ala Ala Asn Gly Ser

325 330 335

Ala Glu Thr Ser Ala Leu Asp Thr Gly Phe Ser Leu Asn Leu Ser Glu

340 345 350

Leu Arg Glu Tyr Thr Glu Gly Leu Thr Glu Ala Lys Glu Asp Asp Asp

355 360 365

Gly Asp His Ser Ser Leu Gln Ser Gly Gln Ser Val Ile Ser Leu Leu

370 375 380

Ser Ser Glu Glu Leu Lys Lys Leu Ile Glu Glu Val Lys Val Leu Asp

385 390 395 400

Glu Ala Thr Leu Lys Gln Leu Asp Gly Ile His Val Thr Ile Leu His

405 410 415

Lys Glu Glu Gly Ala Gly Leu Gly Phe Ser Leu Ala Gly Gly Ala Asp

420 425 430

Leu Glu Asn Lys Val Ile Thr Val His Arg Val Phe Pro Asn Gly Leu

435 440 445

Ala Ser Gln Glu Gly Thr Ile Gln Lys Gly Asn Glu Val Leu Ser Ile

450 455 460

Asn Gly Lys Ser Leu Lys Gly Thr Thr His His Asp Ala Leu Ala Ile

465 470 475 480

Leu Arg Gln Ala Arg Glu Pro Arg Gln Ala Val Ile Val Thr Arg Lys

485 490 495

Leu Thr Pro Glu Ala Met Pro Asp Leu Asn Ser Ser Thr Asp Ser Ala

500 505 510

Ala Ser Ala Ser Ala Ala Ser Asp Val Ser Val Glu Ser Thr Ala Glu

515 520 525

Ala Thr Val Cys Thr Val Thr Leu Glu Lys Met Ser Ala Gly Leu Gly

530 535 540

Phe Ser Leu Glu Gly Gly Lys Gly Ser Leu His Gly Asp Lys Pro Leu

545 550 555 560

Thr Ile Asn Arg Ile Phe Lys Gly Ala Ala Ser Glu Gln Ser Glu Thr

565 570 575

Val Gln Pro Gly Asp Glu Ile Leu Gln Leu Gly Gly Thr Ala Met Gln

580 585 590

Gly Leu Thr Arg Phe Glu Ala Trp Asn Ile Ile Lys Ala Leu Pro Asp

595 600 605

Gly Pro Val Thr Ile Val Ile Arg Arg Lys Ser Leu Gln Ser Lys Glu

610 615 620

Thr Thr Ala Ala Gly Asp Ser

625 630