Patent application title: METHODS FOR FERMENTATIVE PRODUCTION OF MASSOIA LACTONE
Inventors:
IPC8 Class: AC12N114FI
USPC Class:
1 1
Class name:
Publication date: 2019-01-10
Patent application number: 20190010444
Abstract:
The present invention relates to the field of fermentation biotechnology,
more particularly to methods for the fermentative production of massoia
lactone by Aureobasidium species.Claims:
1. A pure culture of Aureobasidium melanogenum that expresses no
functional Aureobasidin A biosynthesis complex gene mRNA when cultured.
2. The pure culture of claim 1, wherein the Aureobasidium melanogenum strain is Aureobasidium melanogenum strain W5-2.
3. The pure culture of claim 2, wherein Aureobasidium melanogenum W5-2 is deposited with Agricultural Research Culture Collection (NRRL) and assigned Accession Number NRRL 67063.
4. The pure culture of claim 1, wherein the Aureobasidium melanogenum GDP1 sequence shares at least 97.5% identity over at least 98.5% of SEQ ID NO:2, preferably 99%-100% identity to over at least 98% of SEQ ID NO:2.
5. The pure culture of claim 1, wherein the Aureobasidium melanogenum TEF1A sequence shares at least 98% identity over at least 94% of SEQ ID NO:8, preferably 99%-100% identity to over at least 99% of SEQ ID NO:8.
6. The pure culture of claim 1, wherein the Aureobasidium melanogenum RBP1 sequence shares at least 91% identity over at least 92% of SEQ ID NO:10, preferably 96%-100% identity to over at least 98% of SEQ ID NO:10.
7. The pure culture of claim 1, wherein the Aureobasidium melanogenum GDP1 sequence shares at least 97.5% identity over at least 98.5% of SEQ ID NO:2, preferably 99%-100% identity to over at least 98% of SEQ ID NO:2, wherein the Aureobasidium melanogenum TEF1A sequence shares at least 98% identity over at least 94% of SEQ ID NO:8, preferably 99%-100% identity to over at least 99% of SEQ ID NO:8 and wherein the Aureobasidium melanogenum RBP1 sequence shares at least 91% identity over at least 92% of SEQ ID NO:10, preferably 96%-100% identity to over at least 98% of SEQ ID NO:10.
8. Use of the pure culture of claim 1 for the fermentative production of massoia lactone.
9. A method of fermentative production of massoia lactone comprising culturing an Aureobasidium melanogenum species in a culture medium comprising high levels of phosphate ions, ammonium ions, calcium ions, at least two trace elements selected from the group consisting of Fe.sup.2+, Cu.sup.2+, Zn.sup.2+ and MoO.sub.4.sup.2-, urea and a carbon source selected from the group consisting of glucose, mannose, xylose and mixtures thereof for a sufficient period of time to produce massoia lactone in a fermentation product.
10. The method of claim 9, wherein the pH of the culture medium is from about 5.5 to about 6.5, preferably 6.0
11. The method of claim 9, wherein the amount of urea present in the culture medium is from about 1.5 g/l to about 2.5 g/l, preferably from about 1.8 g/l to about 2.2 g/l, more preferably about 2 g/l.
12. The method of claim 9, wherein the carbon source present in the culture medium is from about 4% to about 12%, preferably from about 5% to about 12%, preferably from about 5% to about 11%, more preferably from about 5% to about 10%.
13. The method of claim 9, wherein each trace element in the culture medium is present in an amount from about 0.1 .mu.M to about 1.0 mM, from about 1.0 .mu.M to about 1.0 mM, from about 10.0 .mu.M to about 1.0 mM, or from about 100 .mu.M to about 1.0 mM.
14. The method of claim 9, wherein the culture comprises about 10.0 g/l to about 15 g/l, preferably about 12.5 g/l KH.sub.2PO.sub.4, about 0.5 g/l to about 2.0 g/l, preferably about 1.0 g/l Na.sub.2HPO.sub.4, about 3.5 g/l to about 6.5 g/l, preferably about 5.0 g/l (NH4).sub.2SO.sub.4, about 1.0 g/l to about 4.0 g/l, preferably about 2.5 g/l MgSO.sub.4.7H.sub.2O and about 0.10 g/l to about 0.40 g/l, preferably about 0.25 g/l CaCl.sub.2.2H.sub.2O.
15. The method of claim 14, wherein the culture medium further comprises about 2 g/l urea, about 5% to about 10% carbon source and at least two of the trace elements.
16. The method of claim 9, wherein the period of time is for about 4 days to about 12 days, preferably for about 5 days to about 12 days, preferably for about 5 days to about 11 days, preferably for about 6 days to about 11 days, more preferably for about 7 days to about 10 days.
17. The method of claim 9, wherein the Aureobasidium melanogenum is a strain that expresses no functional Aureobasidin A synthase gene mRNA in culture.
18. The method of claim 17, wherein the Aureobasidium melanogenum strain is Aureobasidium melanogenum W5-2.
19. The method of claim 18, wherein Aureobasidium melanogenum W5-2 is deposited with Agricultural Research Culture Collection (NRRL) and assigned Accession Number NRRL 67063.
20. The method of claim 9, which further comprises hydrolyzing the fermentation product by a strong inorganic acid and purifying the massoia lactone from the fermentation product.
21. The method of claim 9, wherein the fermentation product is substantially free of contaminant 3-hydroxyl delta-decalactone (3-hydroxydecan-5-olide).
22. A culture medium for the fermentative production of massoia lactone by Aureobasidium melanogenum species, the culture medium comprising high levels of phosphate ions, ammonium ions, calcium ions, at least two trace elements selected from the group consisting of Fe.sup.2+, Cu.sup.2+, Zn.sup.2+ and MoO.sub.4.sup.2-, urea and a carbon source selected from the group consisting of glucose, mannose, xylose and mixtures thereof.
23. The culture medium of claim 22, wherein the pH of the culture medium is from about 5.5 to about 6.5, preferably 6.0
24. The culture medium of claim 22, wherein the amount of urea present in the culture medium is from about 1.5 g/l to about 2.5 g/l, preferably from about 1.8 g/l to about 2.2 g/l, more preferably about 2 g/l.
25. The culture medium of claim 22, wherein the carbon source present in the culture medium is from about 4% to about 12%, preferably from about 5% to about 12%, preferably from about 5% to about 11%, more preferably from about 5% to about 10%.
26. The culture medium of claim 22, wherein each trace element present in the culture medium is present in an amount from about 0.1 .mu.M to about 1.0 mM, from about 1.0 .mu.M to about 1.0 mM, from about 10.0 .mu.M to about 1.0 mM, or from about 100 .mu.M to about 1.0 mM.
27. The culture medium of claim 22, wherein the culture medium comprises about 10.0 g/l to about 15 g/l, preferably about 12.5 g/l KH.sub.2PO.sub.4, about 0.5 g/l to about 2.0 g/l, preferably about 1.0 g/l Na.sub.2HPO.sub.4, about 3.5 g/l to about 6.5 g/l, preferably about 5.0 g/l (NH4).sub.2SO.sub.4, about 1.0 g/l to about 4.0 g/l, preferably about 2.5 g/l MgSO.sub.4.7H.sub.2O and about 0.10 g/l to about 0.40 g/l, preferably about 0.25 g/l CaCl.sub.2.2H.sub.2O.
28. The culture medium of claim 27, wherein the culture medium further comprises about 2 g/l urea, about 5% to about 10% carbon source and at least two of the trace elements.
29. The culture medium of claim 22, wherein the culture medium further comprises an Aureobasidium melanogenum species.
30. The culture medium of claim 29, wherein the Aureobasidium melanogenum is a strain that expresses no functional Aureobasidin A synthase gene mRNA in culture.
31. The culture medium of claim 30, wherein the Aureobasidium melanogenum strain is Aureobasidium melanogenum W5-2.
32. The culture medium of claim 31, wherein Aureobasidium melanogenum W5-2 is deposited with Agricultural Research Culture Collection (NRRL) and assigned Accession Number NRRL 67063.
33. The culture medium of claim 22 further comprising more than 10 g/l of massoia lactone.
Description:
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to and claim priority to U.S. provisional patent application Ser. No. 62/205,996 filed 17 Aug. 2015. Each application is incorporated herein in its entirety.
SUBMISSION OF SEQUENCE LISTING
[0002] The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is entitled 2577249PCTSequenceListing.txt, created on 15 Aug. 2016 and is 294 kb in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in their entirety.
BACKGROUND OF THE INVENTION
[0003] The present invention relates to the field of fermentation biotechnology, more particularly to methods for the fermentative production of massoia lactone by Aureobasidium species.
[0004] The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference, and for convenience are referenced in the following text by author and date and are listed alphabetically by author in the appended bibliography.
[0005] C-10 massoia lactone [C-10 (5,6-dihydro-6-pentyl-2H-pyran-2-one)] and C-12 massoia lactone [C-12 (5,6-dihydro-6-heptyl-2H-pyran-2-one)] are the major constituent of bark oil of massoia (Cryptocarya massoia) [1]. Massoia lactones can also be found in cane sugar molasses, cured tobacco and the essential oil of Sweet Osmanthus (Osmanthus fragrans) and jasmine [2]. At 20 ppm, it has a taste described as creamy, coconut, green and slightly fruity. Massoia bark oil is used in the flavor industry as an additive in butter and milk flavors (international FEMA code 3744). Current global supply of massoia bark oil comes from Indonesia, using primitive and costly extraction process that destroy precious native forest.
[0006] Massoia lactone is the substrate for the production of saturated delta-decanolide or delta-dodecanolide, which is the key molecule for peach flavor. It can be made by biohydrogenation using a wide range of microorganisms, e.g., yeast (Saccharomyces, Candida, Pichia), molds (Cladosporium), and bacteria (Pseudomonas, Sarcina), [3,4].
[0007] Although methods for the chemical synthesis of massoia lactone have been available, the process is a rather complicated and requires multi-step reactions using costly raw materials and catalysts [5]. Previously, massoia lactone was found in the alkali-hydrolyzed glycolipid secreted by Aureobasidium pullalan A-21 that was cultured under a calcium-deficient condition. It has been reported that, in the presence of calcium, polymalic acid was produced instead [6]. The interaction between various trace elements on the production of massoia lactone has not been reported.
[0008] Certain strains of A. pullulans are known to produce extracellular "heavy oils", or polyol lipids, when CaCO.sub.3 is not present in the medium. The oils have been described as 3,5-dihydroxydecanoyl and 5-hydroxy-2-decenoyl esters of arabitol and mannitol. Medium for oil production is composed of 50 g/l sucrose, 0.6 g/l (w/v) peptone, 0.4 g/l yeast extract, 5 g/l K.sub.2HPO.sub.4, 0.4% g/l MgSO.sub.4*7H.sub.2O, and 1 g/l NaCl [7]. Another reported medium uses nitrate as the sole nitrogen source with low phosphate content and is composed of 120 g/l glucose, 1.5 g/l NaNO.sub.3, 1 g/l KNO.sub.3, 0.05 g/l KH.sub.2PO.sub.4, 0.2 g/l MgSO.sub.4*7H.sub.2O, 2 ppm ZnSO.sub.4*7H.sub.2O, and 0.2 g/l yeast extract [6].
[0009] It is desired to develop new fermentation methods for the production of massoia lactone.
SUMMARY OF THE INVENTION
[0010] The present invention relates to the field of fermentation biotechnology, more particularly to methods for the fermentative production of massoia lactone by Aureobasidium species.
[0011] In one aspect, the present invention provides a method for the fermentative production of massoia lactone by Aureobasidium species. In one embodiment, the Aureobasidium species is Aureobasidium melanogenum. In another embodiment, the A. melanogenum is a strain of A. melanogenum that does not express a functional Aureobasidin A (AbA) biosynthesis complex (aba1) gene mRNA when cultured. In one embodiment, the functional mRNA is not expressed in the culture medium described herein. In a further embodiment, the A. melanogenum that does not express a functional aba1 gene mRNA when cultured is the W5-2 strain of A. melanogenum as described herein. In one embodiment, the Aureobasidium species described herein is cultured in a culture medium described in further detail herein to produce a fermentation product containing massoia lactone. In one embodiment, the culturing is performed for about 4 days to about 12 days, preferably for about 5 days to about 12 days, more preferably for about 7 days to about 10 days. In another embodiment, the culturing is performed at about 25.degree. C. to about 35.degree. C., preferably about 28.degree. C. to about 32.degree. C. In some embodiments, the massoia lactone is purified from the fermentation product using conventional techniques and/or as described in further detail herein.
[0012] In a second aspect, the present invention provides a culture medium for the fermentative production of massoia lactone. In one embodiment, the culture medium comprises high levels of phosphate ions, ammonium ions and calcium ions as described in further detail herein. In some embodiments, the culture medium comprises KH.sub.2PO.sub.4, Na.sub.2HPO.sub.4, (NH4).sub.2SO.sub.4, MgSO.sub.4 and CaCl.sub.2. In another embodiment, the culture medium further comprises at least two trace elements as described in further detail herein. In some embodiments, the trace elements may be selected from Fe.sup.2+, Cu.sup.2+, Zn.sup.2+ and MoO.sub.4.sup.2-. In other embodiments, each trace element that may be present in the culture medium may be present in an amount from about 0.1 .mu.M to about 1.0 mM. In a further embodiment, the culture medium comprises urea as a nitrogen source. In another embodiment, the culture medium comprises glucose, mannose, xylose or mixtures thereof as a carbon source. In one embodiment, glucose is used as the sole carbon source. In one embodiment, the culture medium has a pH from about 5.5 to about 6.5, preferably about 6.0. The fermentation method produces high levels of glycolipids. Biochemically, hydroxyl fatty acids conjugate to produce sugars and eventually produce massoia lactone. Thus, the method produces high levels of massoia lactone--a commercially desirable feature of the present invention.
[0013] In a third aspect, the present invention provides a novel strain of A. melanogenum designated W5-2. In some embodiments, A. melanogenum W5-2 does not express a functional Aureobasidin A biosynthesis complex gene mRNA when cultured. In one embodiment, a functional mRNA is not expressed in the culture medium described herein. In other embodiments, A. melanogenum W5-2 has been deposited with the Agricultural Research Culture Collection (NRRL), 1815 N. University Street, Peoria, Ill. 61604, USA on 28 May 2015 and assigned accession number NRRL 67063.
BRIEF DESCRIPTION OF THE FIGURES
[0014] FIG. 1 shows a phylogenetic dendrogram, based on 18S rRNA gene, the first internal transcribed spacer (ITS1), the 5.8S rRNA gene, the second ITS region and the 5' end of the 28S rRNA gene sequences and constructed from evolutionary distances, showing the position of Aureobasidium strain W5-2 within the radiation of members of the family Dothioraceae, order Dothideales [36]. Numbers at branching points refer to bootstrap percentages (based on 1000 resamplings); only values above 50% are shown. GenBank accession number of each sequence is shown in parentheses.
[0015] FIG. 2 shows results of a GPD1 CDS search by BLASTn against the Whole Genome Shortgun Motifs of Aureobasidium species. This search identified two highly related genomic sequences from Aureobasidium melanogenum CBS 110374 scaffold_4_c3 and Aureobasidium pullulans AY4 contig20 (which is in fact A. melanogenum). Aureobasidium namibiae CBS, Aureobasidium subglaciale EXF-2481 and Aureobasidium pullulans EXF-150 had only partial sequences in the region. The phylogenic tree is generated Blast Tree View at NCBI using fast minimal evolution method.
[0016] FIGS. 3A-3D show the characterization of Nile Red staining substance in W5-2 cells. Cell were cultured in HMDC medium with 10% glucose in shaking flasks for 5 day. Cells were stained with Nile Red and imaged by Confocal microscopy. FIG. 3A: Red channel. FIG. 3B: bright field image. FIG. 3C: Over-lay of FIG. 3A and FIG. 3B. Scale bar=10 .mu.M. FIG. 3D: TLC image of total ethyl acetate extract. The positions for triacylglyceride (TAG) and glycolipid are indicated on the right.
[0017] FIGS. 4A and 4B show GCMS analysis of Aureobasidium isolate W5-2. FIG. 4A: GCMS spectra of methanol-esterified products of methanol and chloroform extract of freeze-dried cell biomass. Arrows indicate the peaks for major fatty acid methyl esters and massoia lactone. FIG. 4B: Database search and the comparison of MS spectrum of the peak shown in upper panel to that of standard massoia lactone, 6-Pentyl-5,6-dihydro-2H-pyran-2-one, shown in lower panel.
[0018] FIG. 5 shows using Central Composite Design (CCD) to optimize concentration of urea, trace elements and glucose.
[0019] FIG. 6 shows glycolipid profiles of various media. Medium composition is shown in Table 2. Seed culture was prepared by inoculating 1.5 ml of frozen 7% DMSO culture into 100 ml of the original HDCM in a 250 ml flask and cultured for 48 hrs at 30.degree. C. The cells were harvested by centrifugation, re-suspended in water and inoculated at 2% into each medium in 250 ml flasks. Cells were cultured at 30.degree. C. with 200 rpm agitation. Samples shown are taken from the 6th day.
[0020] FIGS. 7A and 7B show the effects of trace elements. Media were inoculated with water-washed cell stock cultured in HMDC medium to 0.1 OD.sub.600 and cultured at 30.degree. C. with 200 rpm shaking for 8 days. FIG. 7A: Factorial Design was used to evaluate the effects of FeSO4, MnSO4, ZnSO4, CuCl2 and AlCl3. Run #6 (T2) and Run #12 (T3) were selected for further optimization. FIG. 7B: Factorial Design was used to evaluate the effects of H3BO4, CoCl2 and NaMoO4 based on Medium 2 of step 5.
[0021] FIG. 8 shows production of massoia lactone with various carbon sources. W5-2 was cultured in T2 medium with glucose, mannose, xylose or glycerol as carbon sole source for 4 days. Each data set derived from 3 biological replicates. Error bars indicates SD.
[0022] FIGS. 9A-9C show a comparison of massoia lactone yields in 4 media. The symbols for the media are shown in FIG. 9C. AM refers to a modified A-21M medium (MA-21M) containing 120 g/l glucose, 1.5 g/l NaNO.sub.3, 1.0 g/l KNO.sub.3, 0.05 g/l KH.sub.2PO.sub.4, 0.2 g/l MgSO.sub.4, 0.0056 g/l FeSO.sub.4, 0.2 g/l Yeast Extract (pH 5.5). Seed culture was made in HMDC medium with complete trace elements. FIG. 9A: Massoia lactone. FIG. 9B: Dry biomass yield. FIG. 9C: Residual NH.sub.4.sup.+ in the medium.
[0023] FIG. 10 shows a comparison of cells cultured in T0, T2 and T3 media. Cells were cultured in 2 L fermentor for 9 days.
[0024] FIG. 11 shows the effect of medium pH on massoia lactone yield. T2 medium was adjusted to various pH from pH 4 to pH 6.5. Cells were cultured for 5 days.
[0025] FIGS. 12A-12C show production of massoia lactone. FIG. 12A: GCMS chromatograph of W5-2 Sample cultured in R15 Medium in shake flask. FIG. 12B: GCMS chromatograph of W5-2 Sample cultured in T3 medium in 2 L fermenter. FIG. 12C: database search of ML massoia lactone peak of (FIG. 12B).
DETAILED DESCRIPTION OF THE INVENTION
[0026] The present invention relates to the field of fermentation biotechnology, more particularly to methods for the fermentative production of massoia lactone by Aureobasidium species.
[0027] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the invention belongs.
[0028] The term "about" or "approximately" means within a statistically meaningful range of a value. Such a range can be within an order of magnitude, preferably within 50%, more preferably within 20%, more preferably still within 10%, and even more preferably within 5% of a given value or range. The allowable variation encompassed by the term "about" or "approximately" depends on the particular system under study, and can be readily appreciated by one of ordinary skill in the art.
[0029] The term "as described in further detail herein" means the description of the embodiments set forth in the detailed description of the invention and in the Examples. In this context, the Examples comprise additional details of the general nature of the invention, as well as certain specific aspects not found elsewhere in the specification.
[0030] The term "massoia lactone" as used herein means C-10 massoia lactone [C-10 (5,6-dihydro-6-pentyl-2H-pyran-2-one)] and/or C-12 massoia lactone [C-12 (5,6-dihydro-6-heptyl-2H-pyran-2-one)].
[0031] The term "Aureobasidium melanogenum W5-2" or "A. melanogenum W5-2" or "W5-2" refers to a novel strain of A. melanogenum isolated and characterized as described herein and a culture of which has been deposited as described herein.
[0032] In one aspect, the present invention provides a method for the fermentative production of massoia lactone by Aureobasidium species. In one embodiment, the Aureobasidium species is Aureobasidium melanogenum. In another embodiment, the A. melanogenum is a strain of A. melanogenum that does not express a functional Aureobasidin A (AbA) biosynthesis complex (aba1) gene mRNA when cultured. In one embodiment, the functional mRNA is not expressed in the culture medium described herein. The sequence of a functional aba1 gene is set forth in Genbank Accession No. EU886741 (SEQ ID NO:5). In a further embodiment, the A. melanogenum that does not express a functional aba1 gene mRNA when cultured is the W5-2 strain of A. melanogenum as described herein. In one embodiment, the Aureobasidium species described herein is cultured in a culture medium described in further detail herein to produce a fermentation product containing massoia lactone. In one embodiment, the culturing is performed for about 4 days to about 12 days, preferably for about 5 days to about 12 days, preferably for about 5 days to about 11 days, preferably for about 6 days to about 11 days, more preferably for about 7 days to about 10 days. In another embodiment, the culturing is performed at about 25.degree. C. to about 35.degree. C., preferably at about 27.degree. C. to about 32.degree. C., more preferably at about 28.degree. C. to about 32.degree. C. In a further embodiment, the culturing is performed in shake flasks agitated with a speed from about 175 rpm to about 225 rpm, preferably about 200 rpm. In some embodiments, the massoia lactone is purified from the fermentation product using conventional techniques and/or as described in further detail herein.
[0033] In some embodiments, the massoia lactone is purified from the fermentation product using conventional techniques, e.g., by alkaline hydrolysis and solvent extraction [6]. In other embodiments, a strong inorganic acid is added to the fermentation product to hydrolyze the fermentation product. In one embodiment, the strong organic acid is sulfuric acid or hydrochloric acid. In a further embodiment, the massoia lactone is purified by solvent extraction or distillation. In some embodiments, the solvent is ethyl acetate or hexane.
[0034] In a second aspect, the present invention provides a culture medium for the fermentative production of massoia lactone. In one embodiment, the culture medium comprises high levels of phosphate ions, ammonium ions and calcium ions as described in further detail herein. In some embodiments, the culture medium comprises KH.sub.2PO.sub.4, Na.sub.2HPO.sub.4, (NH.sub.4).sub.2SO.sub.4, MgSO.sub.4 and CaCl.sub.2. In some embodiments, the culture medium comprises about 10.0 g/l to about 15 g/l, preferably about 12.5 g/l KH.sub.2PO.sub.4, about 0.5 g/l to about 2.0 g/l, preferably about 1.0 g/l Na.sub.2HPO.sub.4, about 3.5 g/l to about 6.5 g/l, preferably about 5.0 g/l (NH.sub.4).sub.2SO.sub.4, about 1.0 g/l to about 4.0 g/l, preferably about 2.5 g/l MgSO.sub.4.7H.sub.2O and about 0.10 g/l to about 0.40 g/l, preferably about 0.25 g/l CaCl.sub.2.2H.sub.2O. In another embodiment, the culture medium further comprises at least two trace elements. In a further embodiment, the culture medium comprises at least three trace elements. In an additional embodiment, the culture medium comprises four trace elements. In some embodiments, the trace elements may be selected from Fe.sup.2+, Cu.sup.2+, Zn.sup.2+ and MoO.sub.4.sup.2-. In other embodiments, each trace element that may be present in the culture medium may be present in an amount from about 0.1 .mu.M to about 1.0 mM, from about 1.0 .mu.M to about 1.0 mM, from about 10.0 .mu.M to about 1.0 mM, or from about 100 .mu.M to about 1.0 mM. In a further embodiment, the culture medium comprises urea or ammonium as a nitrogen source. In some embodiments, the urea is present in the culture medium in an amount from about 1.5 g/l to about 2.5 g/l, preferably from about 1.8 g/l to about 2.2 g/l, more preferably about 2 g/l. In some embodiments, ammonium is present in the culture medium in an amount to provide the same amount of nitrogen as provided by the noted urea amounts. In another embodiment, the culture medium comprises glucose, mannose, xylose or mixtures thereof as a carbon source. In some embodiments, the carbon source is present in the culture medium in an amount from about 4% to about 12%, preferably from about 5% to about 12%, preferably from about 5% to about 11%, more preferably from about 5% to about 10%. In some embodiments, glucose is the sole carbon source. In one embodiment, the culture medium has a pH from about 5.5 to about 6.5, preferably about 6.0.
[0035] In a third aspect, the present invention provides a novel strain of A. melanogenum designated W5-2, including a pure culture of the novel strain or the isolated novel strain or the isolated and biologically pure culture of the novel strain. In some embodiments, A. melanogenum W5-2 does not express a functional Aureobasidin A synthase gene mRNA when cultured. In one embodiment, the functional mRNA is not expressed in the culture medium described herein. In other embodiments, A. melanogenum W5-2 was deposited on 28 May 2015 under terms of the Budapest Treating with the Agricultural Research Culture Collection (NRRL) located at 1815 N. University Street, Peoria, Ill. 61604, USA and assigned Accession Number NRRL 67063.
[0036] In some embodiments, Aureobasidium melanogenum and/or Aureobasidium melanogenum strain W5-2 is characterized by the sequence of its genome. In one embodiment, the Aureobasidium melanogenum GDP1 genomic sequence shares at least 97.5% identity over at least 98.5% of SEQ ID NO:2, preferably 99%-100% identity to over at least 98% of SEQ ID NO:2. In another embodiment, the Aureobasidium melanogenum TEF1A genomic sequence shares at least 98% identity over at least 94% of SEQ ID NO:8, preferably 99%-100% identity to over at least 99% of SEQ ID NO:8. In an additional embodiment, the Aureobasidium melanogenum RBP1 genomic sequence shares at least 91% identity over at least 92% of SEQ ID NO:10, preferably 96%-100% identity to over at least 98% of SEQ ID NO:10. In a further embodiment, the Aureobasidium melanogenum GDP1 genomic sequence shares at least 97.5% identity over at least 98.5% of SEQ ID NO:2, preferably 99%-100% identity to over at least 98% of SEQ ID NO:2, the Aureobasidium melanogenum TEF1A genomic sequence shares at least 98% identity over at least 94% of SEQ ID NO:8, preferably 99%-100% identity to over at least 99% of SEQ ID NO:8 and the Aureobasidium melanogenum RBP1 genomic sequence shares at least 91% identity over at least 92% of SEQ ID NO:10, preferably 96%-100% identity to over at least 98% of SEQ ID NO:10.
[0037] In other embodiments, the Aureobasidium melanogenum and/or Aureobasidium melanogenum strain W5-2 is characterized by the amount of fatty acids stored in the fungal cells. In one embodiment, the Aureobasidium melanogenum and/or Aureobasidium melanogenum strain W5-2 fungal cells can store fatty acids at about 40% of its dry weight.
[0038] In accordance with the present invention, it has surprisingly been found that the fermentation of A. melanogenum W5-2 in the culture medium that contains all of the components described herein for the culture medium produces a very high yield of massoia lactone. For example, as shown in the Examples, batch fermentation of A. melanogenum W5-2 in this culture medium produced massoia lactone at a 7 day peak of 10.268 g/l in a 2 L bioreactor, with a volume productivity of 61.11 mg/hr/l. Thus, in one embodiment, the batch fermentation of A. melanogenum W5-2 in this culture medium yields 10.268 g/l of crude massoia lactone. In another embodiment, the batch fermentation of A. melanogenum W5-2 in this culture medium yields more than 10 g/l of crude massoia lactone. In some embodiments, the yield of crude massoia lactone is at least 11 g/l, or at least 12 g/l, or at least 13 g/l, or at least 14 g/l or at least 15 g/l. In other embodiments, the yield of crude massoia lactone is from about 10 g/l to about 25 g/l, or from about 10 g/l to about 24 g/l, or from about 10 g/l to about 23 g/l, or from about 10 g/l to about 22 g/l, or from about 10 g/l to about 21 g/l, or from about 10 g/l to about 20 g/l, or from about 10 g/l to about 19 g/l, or from about 10 g/l to about 18 g/l, or from about 10 g/l to about 17 g/l, or from about 10 g/l to about 16 g/l, or from about 10 g/l to about 15 g/l, or from about 10 g/l to about 14 g/l.
[0039] In some embodiments, the yield of purified massoia lactone from the crude extract is at least 50%. In other embodiments, the yield of purified massoia lactone from the crude extract is more than 5 g/l. In some embodiments, the yield of purified massoia lactone from the crude extract is at least 5.5 g/l, or at least 6 g/l, or at least 6.5 g/l, or at least 7 g/l or at least 7.5 g/l. In other embodiments, the yield of purified massoia lactone from the crude extract from about 5 g/l to about 12.5 g/l, or from about 5 g/l to about 12 g/l, or from about 5 g/l to about 11.5 g/l, or from about 5 g/l to about 11 g/l, or from about 5 g/l to about 10.5 g/l, or from about 5 g/l to about 10 g/l, or from about 5 g/l to about 9.5 g/l, or from about 5 g/l to about 9 g/l, or from about 5 g/l to about 8.5 g/l, or from about 5 g/l to about 8 g/l, or from about 5 g/l to about 7.5 g/l, or from about 10 g/l to about 7 g/l.
[0040] It has surprisingly been found that the fermentation method using strain W5-2, as described herein, has several advantages.
[0041] The method produces high levels of glycolipids. Biochemically hydroxyl fatty acids conjugate to produce sugars and eventually produce massoia lactone. Thus, the method produces high levels of massoia lactone--a commercially desirable feature of the invention.
[0042] Massoia lactone is exuded into the medium and about 80% of the supernatant contains massoia lactone--reflecting the ability to obtain high amounts of massoia lactone.
[0043] The method can produce more than 10 g/l massoia lactone within 5 days at lab scale using glucose as a sole carbon source.
[0044] The crude extract has more than 10 g/l of massoia lactone. Upon purification the yield is more than 5 g/l of the crude extract, which is at least about 50% distillation recovery.
[0045] Use of 2 liter bioreactor yields high amounts of massoia lactone.
[0046] The method is highly efficient--the crude extract has less of impurities, including negligible or minimum intermediates. The method is highly time and cost efficient.
[0047] The massoia lactone is capable of producing multiple odors and/or flavors, e.g., coconut, waxy, oily aroma, creamy, green and slightly fruity flavors and/or odors. The massoia lactone can be converted into delta-decanolide or delta-dodecanolide to produce a peachy flavor and/or odor.
[0048] The practice of the present invention employs, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA, genetics, immunology, cell biology, cell culture and transgenic biology, which are within the skill of the art. See, e.g., Maniatis et al., 1982, Molecular Cloning (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.); Sambrook et al., 1989, Molecular Cloning, 2nd Ed. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.); Sambrook and Russell, 2001, Molecular Cloning, 3rd Ed. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.); Ausubel et al., 1992), Current Protocols in Molecular Biology (John Wiley & Sons, including periodic updates); Glover, 1985, DNA Cloning (IRL Press, Oxford); Russell, 1984, Molecular biology of plants: a laboratory course manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.); Anand, Techniques for the Analysis of Complex Genomes, (Academic Press, New York, 1992); Guthrie and Fink, Guide to Yeast Genetics and Molecular Biology (Academic Press, New York, 1991); Harlow and Lane, 1988, Antibodies, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.); Nucleic Acid Hybridization (B. D. Hames & S. J. Higgins eds. 1984); Transcription And Translation (B. D. Hames & S. J. Higgins eds. 1984); Culture Of Animal Cells (R. I. Freshney, Alan R. Liss, Inc., 1987); Immobilized Cells And Enzymes (IRL Press, 1986); B. Perbal, A Practical Guide To Molecular Cloning (1984); the treatise, Methods In Enzymology (Academic Press, Inc., N.Y.); Methods In Enzymology, Vols. 154 and 155 (Wu et al. eds.), Immunochemical Methods In Cell And Molecular Biology (Mayer and Walker, eds., Academic Press, London, 1987); Handbook Of Experimental Immunology, Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986); Riott, Essential Immunology, 6th Edition, Blackwell Scientific Publications, Oxford, 1988; Fire et al., RNA Interference Technology: From Basic Science to Drug Development, Cambridge University Press, Cambridge, 2005; Schepers, RNA Interference in Practice, Wiley-VCH, 2005; Engelke, RNA Interference (RNAi): The Nuts & Bolts of siRNA Technology, DNA Press, 2003; Gott, RNA Interference, Editing, and Modification: Methods and Protocols (Methods in Molecular Biology), Human Press, Totowa, N.J., 2004; Sohail, Gene Silencing by RNA Interference: Technology and Application, CRC, 2004.
EXAMPLES
[0049] The present invention is described by reference to the following Examples, which are offered by way of illustration and are not intended to limit the invention in any manner. Standard techniques well known in the art or the techniques specifically described below were utilized.
Example 1
Materials and Methods
[0050] Isolation of Microbial Strains:
[0051] Microbial samples were collected from various regions in Singapore. Samples were mixed with 100 ml autoclaved sea water and incubated overnight at 28.degree. C. A 100 .mu.l of the overnight culture was withdrawn and streaked on modified seawater-YPD (Yeast Peptone Dextrose) medium (containing 1 g/l peptone, 2 g/l yeast extract, 4 g/l glucose, and 8 g/l agar, pH 7), which was further supplemented with 0.5 .mu.g/ml Nile red and an antibiotic selected from ampicillin (25 .mu.g/ml), kanamycin (25 .mu.g/ml) and streptomycin (100 .mu.g/ml). Potato dextrose agar (PDA) was also used for the initial screening. The plates were incubated at 28.degree. C. for 48 hr and the strongly Nile red staining strains were identified by examining the plates under a Nikon C-DSS230 stereomicroscope microscope (Nikon, Japan) equipped with Digital Sight DS-L1 camera. Candidate strains were purified by 2 rounds of single colony isolation on seawater-YPD plates followed by verification of Nile red staining in small scale liquid cultures. Florescence was measured using the TECAN infinite M200 fluorometer with the excitation wave-length and emission wave-length set at of 530 nm and 575 nm respectively (TECAN, USA).
[0052] Phylogenetic Analysis of the Microbial Strains by ITS Sequencing:
[0053] Yeast isolates were cultured in YPD medium at 30.degree. C. Genomic DNAs were extracted from 2 ml of 48 hr cultures using the MasterPure.TM. Yeast DNA Purification Kit (Epicentre Biotechnologies, USA) according to the manufacturer's instructions. PCR amplification reactions were performed in 40 .mu.l 1.times. buffer with 2.5 mM dNTP, 50 .mu.M each primer, 50 ng of total DNA and 3 units of Taq DNA polymerase (i-DNA Biotechnology, Singapore). PCR cycling conditions were as followed: 95.degree. C./10 min, 30 cycles of 95.degree. C./1 min, 61.8.degree. C./1 min and 72.degree. C./1 min and final extension for 5 min/72.degree. C. The ITS1(5'-tccgtaggtgaacctgcgg; SEQ ID NO:3) and ITS4 (5'-tcctccgcttattgatatgc SEQ ID NO:4) [8] primers were used to amplify the ITS region of the nuclear rRNA operon spanning the 3' end of the 18S rRNA gene, the first internal transcribed spacer (ITS1), the 5.8S rRNA gene, the second ITS region and the 5' end of the 28S rRNA gene. [9]. Gel-purified PCR products were sequenced with the Big-Dye sequencing method in Applied Biosystems 3730.times.1 DNA Analyzer (Life technologies, USA). Sequences were analyzed by BLAST against the NCBI database and aligned using the CLUSTAL W tool in MEGA version 5.05 [10]. Phylogenetic analyses were performed by the Neighbour-Joining [11], Maximum-Likelihood [12] and Maximum-Parsimony methods [13] using the MEGA version 5.05 with the bootstrap values set at 1000 replications.
[0054] Small Scale Culture and Fed-Batch Fermentation:
[0055] Aureobasidium strain W5-2 was cultured in 100 ml liquid medium in 250 ml shake flasks, agitated with a speed of 200 rpm and constant temperature of 30.degree. C. The High Density Culture Medium (HDCM) developed for Rhodotorula glutinis [14] was used as the basic culture medium. It contains 90 g/l glucose, 12.5 g/l KH.sub.2PO.sub.4, 1.0 g/l Na.sub.2HPO.sub.4, 5.0 g/l (NH4).sub.2SO.sub.4, 1.9 g/l yeast extract, 2.5 g/l MgSO.sub.4.7H.sub.2O, 0.25 g/l CaCl.sub.2.2H.sub.2O and 0.25 ml/l trace element mix (pH 5.5). Trace elements mix was made in 5N HCl and contains 40 g/l FeSO.sub.4.7H2O, 40 g/l CaCl.sub.2.2H.sub.2O, 10 g/l MnSO.sub.4.7H.sub.2O, 10 g/l AlCl.sub.3.6H.sub.2O, 4 g/l CoCl.sub.2, 2 g/l ZnSO.sub.4.7H.sub.2O, 2 g/l Na.sub.2MoO.sub.4, 1 g/l CuCl.sub.2.2H.sub.2O and 0.5 g/l H.sub.3BO.sub.3. Where indicated, levels of trace elements and various nitrogen sources were varied. For comparison purpose, the strain was also cultured in the A-21M medium reported previously [6], which contains 120 g/l glucose, 1.5 g/l NaNO.sub.3, 1.0 g/l KNO.sub.3, 0.05 g/l KH.sub.2PO.sub.4, 0.2 g/l MgSO.sub.4.7H.sub.2O, 2 ppm ZnSO.sub.4, 0.2 g/l yeast extract (pH 5.5).
[0056] Fed-batch fermentation was carried out in a 2 L Biostat B plus bioreactor (Sartorius Stedim Biotech, Germany). Dissolved oxygen level (pO.sub.2) and air flow was maintained at 30% and 1.5 vvm, respectively. 25 ml samples were taken daily to monitor glucose, ammonium, NO.sup.2- and NO.sup.3- levels.
[0057] Optimization of Massaio Lactone Production by Design of Experiment (DOE):
[0058] Optimization of massaio lactone production by Design of Experiment (DOE) was aided with the Design-Expert.RTM. V8 Software (Stat-Ease, USA) using both the Optimised Factorial Design and Central Composite Design (CCD). Seed cultures prepared in the HDCM medium were harvested by centrifugation, washed with sterile distilled water and suspended in sterile distilled water. A fraction of which (2 ml) was inoculated into 100 ml of the respective designed medium in a 250 ml shake flask, which was cultured in a 30.degree. C. shaking platform agitated at 200 rpm. Culture samples (15 ml) were taken daily for the analyses of cell biomass, OD.sub.600 and metabolites.
[0059] Extraction and Quantification of Glycolipids:
[0060] Ethyl acetate was added to cell culture at a volumetric ratio of 1:1 in a 15 ml Falcon tube. The mixture was vortexed vigorously for 20 seconds; centrifuged at 3,500 g for 10 minutes and 1 ml of the upper phase was transferred to a 1.5 ml Eppendorf tube and left to air dry overnight at room temperature in an exhaust hood. The resultant dried residue was weighed with a microbalance before being added with 10 .mu.l menthol in methanol (10% w/v) (as the internal standard) and 300 .mu.l of 2M NaOH. The suspended mixture was allowed to hydrolyze overnight in a shaking platform at room temperature. After mixing with 150 .mu.l of 5M H.sub.2SO.sub.4, 450 .mu.l ethyl acetate was added and vortexed vigorously. After centrifugation, the upper phase was used for GCMS analysis directly. Alternatively, glycolipids were extracted directly from wet cell biomass collected by centrifugation from 10 ml culture. 2 ml of 72% H.sub.2SO.sub.4 was added to the cell pellet, mixed well and allowed to stand for half an hour and then mixed with 4 ml water. After boiling for one hour, 4 ml of the mixture was added with equal volume of ethyl acetate; vortexed vigorously for 20 seconds; centrifuged at 3,500 g for 10 minutes and 1 ml of the upper phase was analyzed by GCMS or thin-layer chromatography (TLC). Conditions used TLC were as described previously [15]. Hexane can be used in place of ethyl acetate in this procedure. HCl can be used in place of H.sub.2SO.sub.4 in this procedure.
[0061] Preparation and Quantification of Massoia Lactone:
[0062] Equal volume of H.sub.2SO.sub.4 was added to 2 ml of cell culture in a 15 ml Falcon tube. Samples were vortexed briefly and left in room temperature for 30 mins. After adding 4 ml of water, Falcon tubes were boiled in a water-bath for 60 min; cooled for 10 mins at room temperature, and then 4 ml of ethyl acetate was added into the tubes, which were mixed vigorously with a vortex for 20 seconds. Samples were centrifuged for 10 mins at 3,500 ref and 1 ml of the top organic layer was transferred to a 2 ml glass vial containing 50 mg of Na.sub.2SO.sub.4 and 10 .mu.l menthol solution in methanol (10%). Massoia lactone was quantified using GCMS using menthol as the internal standard. HCl can be used in place of H.sub.2SO.sub.4 in this procedure.
[0063] Quantification of Fatty Acid:
[0064] Cell biomass was collected from 20 ml culture by centrifugation and dried in a 60.degree. C. oven until constant weight is reached. The resultant dried pellets were frozen in liquid nitrogen and grinded to a fine powder using mortar and pestle. A 250 mg sample was transferred to a 15 ml Falcon tube and then mixed with 2 ml of 72% H.sub.2SO.sub.4 and 10 .mu.l of 10% (w/v) pentadeconoic acid in methanol (as the internal standard). The samples were hydrolyzed at room temperature for 30 mins and then mixed with 4 ml water. After boiling for 1 hour, a 500 .mu.l fraction was transferred to a 2 ml Eppendorf tube and fatty acids were extracted by mixing with 1 ml methanol/chloroform mixture (1:1 v/v). After centrifugation, the bottom layer was collected by pipetting and washed once with PBS buffer in an Eppendorf tube. The methanol/chloroform bottom layer was collected after centrifugation and left to dry at room temperature in an exhaust hood. 300 .mu.l petroleum ester (Fisher Chemicals, CAS: 64742-49-0)/benzene (QREC Asia SDN BDH, CAS 71-43-2) mixture (1:1 v/v) and 300 .mu.l 0.4 M KOH in methanol was added to solubilize the dried residues. Esterification was performed at room temperature for 3 hours. After separation by centrifugation, 50 .mu.l of the top layer was diluted with 450 .mu.l of methanol and subjected to analysis by GC-MS.
[0065] GC-Ms Analysis:
[0066] GC-MS analysis was performed using GCMS-QP2010 Ultra (Shimadzu Corporation, Japan). Samples (10) were injected into a HP-88 column (30 m.times.0.25 mm ID.times.0.20 .mu.m) (Agilent Technologies, USA) and run with helium as the carrier gas maintained at 10 psi. A split-less injection time of 0.5 min was used. The GC started at an initial temperature of 50.degree. C. for 1 minute, ramped at 15.degree. C. per minute up to 150.degree. C. and 3.degree. C. per minute to a final temperature 240.degree. C. The spectrometer was scanned from 41-400 amu. The compounds were identified by searching against the NIST 08 mass spectral library. Quantification of fatty acid ester and massoia lactone was done by comparing the peak area between the target compounds and the respective internal standards.
[0067] Other Quantification Methods:
[0068] Glucose levels were quantified using a Shimadzu Prominence UFLC (Shimadzu, Japan). Samples were run through an Aminex HPX-87H column (Bio-rad, USA) maintained at 50.degree. C. 5 mM H.sub.2SO.sub.4 was used as the mobile phase and run at a flow rate of 0.7 ml/min. Total nitrates, nitrites and ammonia levels were determined using the method as described [16, 17].
[0069] RNA Sampling and RNA-Sequencing:
[0070] Cell cultures (1 ml) were collected at day 1, 2, 3 and RNAs were immediately extracted with RiboPure.TM. RNA Purification Kit, yeast (Life Technologies, USA). After determination of the RNA quantity and quality by Nanodrop and agarose gel electrophoresis, the RNA samples were sent to Macrogen Inc. (Korea) for cDNA shotgun library construction and sequencing using Illumina Hiseq 2000.
[0071] Computational Analysis:
[0072] Computational analysis was performed in the Galaxy platform (http://galaxyproject.org/) installed locally [18]. Raw reads (100 bp paired-end) were analyzed with NGS QC toolkit [19] for their quality. Then, Tophat and Cufflinks [20-22] were used to identify differential gene/transcript expression based on published genome sequences as the references. de novo assembly was performed with Trinity [23, 24], which produced .about.18 k isoforms or transcripts. Differentially expressed (DE) transcripts and expression profile clusters were done with Bioconductor with rsem and edgeR packages [25, 26].
Example 2
Identification of Massoia Lactone-Producing Microbial Strains
[0073] Nile red is an uncharged hydrophobic molecule whose fluorescence is strongly influenced by the polarity of its environment and it is often used as a marker for hydrophobic substances, such as lipid, glycolipids and hydrophobic proteins [27-29]. By screening water and soil samples obtained from local costal environment using Nile red as a marker, 32 candidates were identified that showed significant red fluorescence, among which strain W5-2 was identified as fungus closely related to Aureobasidium species based on the sequence comparison of the rDNA ITS region (SEQ ID NO. 1) (FIG. 1). W5-2 colonies turned black after 7 days of culture on solid medium (not shown).
[0074] Because Aureobasidium species are identified by phylogenetic analysis of their whole genome sequences as well as certain phylogenetically important genes, such as house-keeping genes encoding Actin, .beta.-tubulin, calmodulin, chytin synthase, NAD-dependent glycerol-3-phosphate dehydrogenase and translation elongation factor 1.alpha. (TEF1A), the whole transcriptome of W5-2 was chosen to compare those of the type Aureobasidium strains [30].
[0075] The overall alignment rates of raw reads to the 4 reference genomes of Aurebasidium species [31] were low, .about.55.7% to A. melanogenum and .about.15-19% to the rest Aureobasidium species (Table 1). Therefore, de novo assembly of RNA-seq data was performed using the Trinity program [32], producing a sequence library of .about.18 k isoforms/transcripts. The overall alignment rate of raw reads to this local reference was increased to above 95%.
TABLE-US-00001 TABLE 1 Mapping Rates to Reference Genomes of Aurebasidium Species T0-1 d T0-2 d T0-3 d T2-1 d T2-2 d T2-3 d Average A. melanogenum 60.47% 52.76% 52.10% 58.24% 56.73% 54.06% 55.72% A. pullulans 21.68% 15.71% 15.81% 16.80% 15.06% 13.86% 16.49% A. subglaciale 19.80% 14.23% 14.41% 15.46% 13.48% 12.41% 14.97% A. namibiae 24.90% 18.11% 18.23% 20.08% 18.04% 16.32% 19.28% Note: Raw reads were mapped to reference genome using TopHat software[33]. RNA samples were extracted from W5-2 cell culture in Medium T0 and Medium T2 at Day, 1, 2 and 3 respectively.
[0076] DNA sequence divergence in GPD1 gene is used as an important indicator for phylogenetic analysis in Aureobasidium species [30]. GPD1 CDS sequence (SEQ ID NO:2) was searched by BLASTn against the Whole Genome Shortgun sequences of Aureobasidium species at NCBI. Six highly related sequences were identified. Phylogenic tree generated Blast Tree View using fast minimal evolution method is shown in FIG. 2, which clearly places the W5-2 GPD1 sequence between A. melanogenum CBS 110374/A. pullulans AY4, which has been re-classified as A. melanogenum [30], and A. namibiae CBS 147.97/A. subglaciale EXF-2481. W5-2 showed highest divergence from A. pullulans EXF-150 and lowest divergence to A. melanogenum.
[0077] A. pullulans is known to produce antibiotic aureobasidin A [34], which is made by a huge polyketide synthase Aba1 [35]. A search of ABA1 CDS (Genbank no. EU886741) against the W5-2 whole transcriptome failed to identify any homologs in the genome. Therefore, strain W5-2 does not encode a functional ABA1 gene and is not likely to produce any antibiotics.
[0078] Confocal imaging confirmed that Nile red stained the cytoplasm intensely with little signal in the cytoplasmic membrane, suggesting the high accumulation of hydrophobic substance in the cells (FIG. 3C). Fatty acid profiling by GCMS revealed that the total ethyl acetate extract contained 52.28% oleic acid, 33.9% palmitic acid, 3.98% linoleic acid, 1.31% palmatolic acid and about 1.3% of long chain (C24 and above) fatty acids (Table 2). Thin layer chromatography (TLC) confirmed the production of triacylglyceride (TAG) and glycolipids (FIG. 3D). Unexpectedly, the GCMS profile showed a significant peak with a retention time of approximately 25.7 min, which had >93% similarity to massoia lactone, i.e., 6-pentyl-5,6-dihydro-2H-pyran-2-one (FIGS. 4A and 4B). Sensory test of the dried cell pellet confirmed the presence a strong coconut-like aroma.
TABLE-US-00002 TABLE 2 Fatty Acid Profile of W5-2 C16 C16:1 C18 C18:1 C18:2 C24 W5-2 33.91% 1.31% 7.24% 52.28% 3.98% 1.29%
Example 3
Medium Optimization Using Central Composite Designs (CCD)
[0079] To improve massoia lactone production, the Rhodotorula glutinis high density (HMDC) medium [14] was modified by changing the levels of nitrogen source (urea), carbon source (glucose) and trace element mix, which contains FeSO.sub.4.7H.sub.2O, CaCl.sub.2.2H.sub.2O, MnSO.sub.4, AlCl.sub.3.6H.sub.2O, CoCl.sub.2, ZnSO.sub.4.7H.sub.2O, Na.sub.2MoO.sub.4.2H.sub.2O, CuCl.sub.2.2H.sub.2O and H.sub.3BO.sub.4. Medium compositions are shown in Table 3. Massoia lactone production was low, ranging from 0.05 mg/l (Run 6) to 1.61 mg/l (Run 16) (FIG. 5). While there were obvious differences amongst the runs, none of the parameters appeared to significantly influence the production by ANOVA analysis (p<0.05) (Table 4). Since massoia lactone produced in A. pullulans has been reported to derive from glycolipid [6], we monitored glycolipid levels by TLC. Again, CCD was employed to optimize the nitrogen source and carbon source in HMDC medium, with urea and yeast extract set as category factors while glucose level was set at 7.5, 20, 50, 80, 92.4 g/l respectively. In addition, the trace element mix was set at 0.034, 0.2, 0.6, 1.0, 1.17 ml per litre medium respectively (Table 5). High variations in glycolipid profiles were observed: Run No. 15 appeared to be the best combination for glycolipid production (FIG. 6), with 285 mg/l massoia lactone present in the acid hydrolyzed glycolipid products. Therefore, we chose a medium containing high level of glucose (.about.100 g/l), 2 g/l urea as the sole nitrogen source and 0.6 ml original HMDC trace element mix for subsequent medium optimizations. For convenience, this medium is referred as the Run 15 (R15) medium.
TABLE-US-00003 TABLE 3 Optimization of Nitrogen source, Carbon Source and Trace Elements by CCD Run No. Urea (g/L) Glucose (g/l) Trace (ml/l) 1 2.89 36.21 0.95 2 1.11 83.78 0.24 3 2 60 1.2 4 2 60 0.6 5 0.5 60 0.6 6 2 60 0 7 2.89 36.21 0.24 8 2 60 0.6 9 2 60 0.6 10 2 60 0.6 11 3.5 60 0.6 12 1.11 83.78 0.957 13 1.11 36.21 0.96 14 2 20 0.6 15 2 60 0.6 16 2 60 1.00 17 2.89 83.78 0.24 18 1.11 36.21 0.24 19 2 100 0.6 20 2.89 83.78 0.96
TABLE-US-00004 TABLE 4 Anova Analysis of Table 3 Sum of Mean F p-value Source Squares df Square Value Prob > F Remarks Model 0.75 3.00 0.25 1.98 0.1580 not significant A-Trace 0.23 1.00 0.23 1.86 0.1919 elements B-Urea 0.00 1.00 0.00 0.02 0.8813 C-Glucose 0.51 1.00 0.51 4.05 0.0612 Residual 2.02 16.00 0.13 Lack of Fit 1.87 11.00 0.17 5.95 0.0308 significant Pure Error 0.14 5.00 0.03 Cor Total 2.77 19.00 Std. Dev. 0.36 R-Squared 0.27 Mean 0.59 Adj R- 0.13 Squared C.V. % 60.42 Pred R- -0.30 Squared PRESS 3.60 Adeq 4.27 Precision
TABLE-US-00005 TABLE 5 Medium Compositions of Central Composite Design 1 (CCD1) Nitrogen Glucose Trace element lactone Run source (g/l) mix (ml/l) titre (mg/l) 1 Urea 7.57 0.6 0.256 2 Yeast extract 50 0.03 4.192 3 Yeast extract 50 0.6 2.384 4 Yeast extract 7.57 0.6 1.386 5 Yeast extract 80 0.2 2.594 6 Yeast extract 20 0.2 3.257 7 Yeast extract 20 1 4.130 8 Urea 80 0.2 3.082 9 Urea 50 1.17 4.978 10 Yeast extract 50 0.6 3.100 11 Yeast extract 80 1 3.366 12 Urea 20 1 1.853 13 Urea 20 0.2 4.103 14 Urea 80 1 4.935 15 Urea 92.43 0.6 6.731 16 Urea 50 0.6 2.300 17 Urea 50 0.6 5.272 18 Urea 50 0.6 3.011 19 Yeast extract 50 0.6 4.325 20 Yeast extract 50 1.17 2.510 21 Yeast extract 50 0.6 2.651 22 Urea 50 0.6 5.715 23 Urea 50 0.03 4.990 24 Yeast extract 92.43 0.6 0.934 25 Urea 50 0.6 3.700 26 Yeast extract 50 0.6 4.855 Note: urea and yeast extract were both set at 1.9 g/l.
Example 4
Optimization of Trace Elements Using Factorial Designs
[0080] FeSO.sub.4, MnSO.sub.4, ZnSO.sub.4, CuCl.sub.2, AlCl.sub.3 were supplemented to the R15 medium using Factorial Optimal Design at the same concentration [14], either individually or in combinations (Table 6). Results showed that Run #12 which was supplemented with Fe.sup.2+, Zn.sup.2+ and Cu.sup.2+ (named as T3 medium hereafter) produced the highest level of massoia lactone, reaching 433 mg/l on day 8. Run #6 in which Mn.sup.2+ and Zn.sup.2+ were both supplemented (named as T2 medium hereafter) ranked 2.sup.nd, yielding 218 mg/l massoia lactone (FIG. 7A; Table 6). In contrast, Basal medium (Run 2, referred to as T0 medium) with CoCl.sub.2, HBO.sub.3 and NaMoO.sub.4 only produced only 58 mg/l massoia lactone, more than 14 folds lower than with T3 medium (FIG. 7A, Table 6). Anova analysis showed that ZnSO.sub.4, CuCl.sub.2, FeSO.sub.4, ZnSO.sub.4, FeSO.sub.4--CuCl.sub.2, FeSO.sub.4--AlCl.sub.3, and CuCl.sub.2--AlCl.sub.3 significantly affected massoia lactone production (Tables 6 and 7).
TABLE-US-00006 TABLE 6 Trace Elements Part 1 Run # FeSO.sub.4 MnSO.sub.4 ZnSO.sub.4 CuCl.sub.2 AlCl.sub.3 1 Y N Y Y Y 2 N N N N N 3 Y Y N Y Y 4 N Y N N Y 5 N N N N Y 6 N Y Y N N 7 N N Y N Y 8 Y N Y N N 9 N N Y Y N 10 Y N N N Y 11 Y N N Y N 12 Y N Y Y N 13 Y N N N N 14 N Y Y Y Y 15 Y N N Y N 16 Y Y N N Y 17 Y Y N N N 18 Y Y Y Y Y 19 N Y N Y N 20 Y Y Y Y N 21 N N N Y Y Note: Basal medium (T0 medium) contained 100 g/l glucose, 12.5 g/l KH.sub.2PO.sub.4, 1.0 g/l Na.sub.2HPO.sub.4, 5.0 g/l (NH4).sub.2SO.sub.4, 2 g/l urea, 2.5 g/l MgSO.sub.4.cndot.7H2O, 0.25 g/l CaCl.sub.2.cndot.2H2O, 2.4 mg/l CoCl.sub.2, 0.3 mg/l HBO.sub.3 and 1.2 mg/l NaMoO.sub.4, pH 5.5. 0.6 ml of trace element mix was added to each litre of medium. Where indicated by N, the trace element was omitted in the trace element mix. The final medium contained various combinations of FeSO.sub.47H.sub.2O (24 mg/l), MnSO.sub.4 (6 mg/l), ZnSO.sub.4 (1.2 mg/l) and CuCl2 (0.6 mg/l).
TABLE-US-00007 TABLE 7 Anova Analysis of Table 6 Sum of Mean F p-value Source Squares df Square Value Prob > F Remarks Model 469.03 15.00 31.27 17.67 0.0025 significant A-FeSO.sub.4 6.58 1.00 6.58 3.72 0.1118 B-MnSO.sub.4 5.67 1.00 5.67 3.20 0.1335 C-ZnSO.sub.4 305.29 1.00 305.29 172.50 <0.0001 significant D-CUCl.sub.2 22.61 1.00 22.61 12.78 0.0160 significant E-AlCl.sub.3 3.46 1.00 3.46 1.95 0.2211 AB 0.87 1.00 0.87 0.49 0.5151 AC 69.62 1.00 69.62 39.34 0.0015 significant AD 22.14 1.00 22.14 12.51 0.0166 significant AE 16.67 1.00 16.67 9.42 0.0278 significant BC 2.88 1.00 2.88 1.63 0.2579 BD 0.44 1.00 0.44 0.25 0.6408 BE 5.87 1.00 5.87 3.32 0.1282 CD 0.18 1.00 0.18 0.10 0.7598 CE 0.29 1.00 0.29 0.16 0.7043 DE 19.93 1.00 19.93 11.26 0.0202 significant Residual 8.85 5.00 1.77 Cor Total 477.88 20.00 Std. Dev. 1.33 R-Squared 0.98 Mean 21.66 Adj R- 0.93 Squared C.V. % 6.14 Pred R- 0.29 Squared PRESS 339.46 Adeq 16.34 Precision
[0081] In another experiment, the effects of the remaining trace elements, i.e., CoCl.sub.2, HBO.sub.3 and NaMoO.sub.4 were tested. Results showed that CoCl.sub.2 (2.4 mg/1) strongly inhibited massoia lactone production (p<0.0001) while NaMoO.sub.4 (1.2 mg/1) significantly improved the production (p<0.05). HBO.sub.3 (0.3 mg/1) did not appear to have significant effect (Tables 8 and 9). The best medium was Run 12, with a massoia lactone yield of 1300 mg/l (FIG. 7B). Notably, this medium contains high level of CaCl.sub.2 (0.25 g/l CaCl.sub.2.2H.sub.2O).
TABLE-US-00008 TABLE 8 Trace Elements Part 2 Run # CoCl.sub.2 NaMoO.sub.4 H3BO.sub.4 1 N Y Y 2 Y Y N 3 N N N 4 N Y N 5 N N N 6 Y N Y 7 N Y Y 8 N N Y 9 Y Y Y 10 Y N N 11 N N Y 12 N Y N 13 Y Y Y Note: Media were inoculated to 0.1 OD.sub.600 with water-washed cell stock cultured in HMDC medium and cultured at 30.degree. C. with 200 rpm shaking for 8 days. Basal medium was T0 medium (Table 6) with various combinations of CoCl.sub.2 (2.4 mg/l), HBO.sub.3 (0.3 mg/l) and NaMoO.sub.4 (1.2 mg/l).
TABLE-US-00009 TABLE 9 Anova Analysis of Table 8 Sum of Mean F p-value Source Squares df Square Value Prob > F Remarks Model 2702668.48 6.00 450444.75 47.99 <0.0001 significant A-CoCl.sub.2 2431273.40 1.00 2431273.40 259.01 <0.0001 significant B-NaMoO.sub.4 60353.96 1.00 60353.96 6.43 0.0443 significant C-H.sub.3BO.sub.4 769.68 1.00 769.68 0.08 0.7842 AB 21411.70 1.00 21411.70 2.28 0.1817 AC 320.50 1.00 320.50 0.03 0.8595 BC 18462.23 1.00 18462.23 1.97 0.2103 Residual 56320.37 6.00 9386.73 Lack of Fit 3671.82 1.00 3671.82 0.35 0.5805 not significant Pure Error 52648.56 5.00 10529.71 Cor Total 2758988.86 12.00 Std. Dev. 96.89 R- 0.98 Squared Mean 741.48 Adj R- 0.96 Squared C.V. % 13.07 Pred R- 0.91 Squared PRESS 243152.35 Adeq 15.75 Precision
Example 5
Utilization of Various Carbon Sources by A. melanogenum W5-2
[0082] To see if strain W5-2 is able to utilize other carbon sources for the production of massoia lactone, glucose in T2 medium was replaced with the same concentrations of D-(+)-mannose, D-(+)-xylose and glycerol. Mannose was essentially as efficiently utilized as glucose. The strain also efficiently converted xylose to massoia lactone although the yield was about 20% lower than with glucose under the conditions tested. Glycerol was a poor carbon source (FIG. 8).
Example 6
Fed-Batch Fermentation
[0083] To verify the performance of the optimized media, fed-batch fermentation was performed in 2 L bioreactors using T0, T2 and T3 media. As the original A-21M medium barely supports the growth of W-52, a modified A-21M medium (MA-21M) was used as a reference. MA-21M contained 120 g/l glucose, 1.5 g/l NaNO.sub.3, 1.0 g/l KNO.sub.3, 0.05 g/l KH.sub.2PO.sub.4, 0.2 g/l MgSO.sub.4, 0.0056 g/l FeSO.sub.4, 0.2 g/l Yeast Extract (pH 5.5). Indeed, both T2 and T3 media showed drastically improved massoia lactone production compared to the T0 medium (FIG. 9A). Best result was observed with T3 medium, in which massoia lactone level peaked at Day 7, reaching 10.268 g/l, with a volumetric productivity of 61.11 mg/hr/l. In T2 medium, massoia lactone production was significantly lower than T3 medium throughout the time course. Maximal production was delayed at least 3 days with a titre of 6.924 g/l and volumetric productivity of 28.85 mg/hr/l. In contrast, maximal titre for T0 medium was only 0.441 g/l observed at Day 10, with a volumetric productivity of 1.84 mg/hr/l. The MA-21M medium performed better than T0 medium, peaking Day 9 with a titre of 1.777 g/l and volumetric productivity of 8.23 mg/hr/l. Thus, the volumetric productivity in T3 and T2 medium were 7.43-fold and 3.51-fold higher than that of A-21M medium, respectively.
[0084] In T0 and T2 medium, cells produced much higher biomass at the cost of the desired metabolite (FIG. 9B). Nitrogen source in both T2 and T3 media were rapidly consumed and became depleted after Day 2. In contrast, NH.sup.4+ level remained high in T0 medium until Day 8 (FIG. 9C). The cells showed very different colors: cells contained strong black pigments, presumably melanin, in T2 and T3 media. In stark contrast with previous report [6], the result suggests that the production of black pigment was associated with high massoia lactone production.
Example 7
Effect of Medium pH
[0085] W5-2 cells cultured in YPD medium was cultured in T2 medium adjusted to various pH values ranging from pH 4 to pH 6.5. The maximal titre was observed with pH6.0. Slight reduction of yield was seen for pH 5.5 and 6.5 (FIG. 11).
Example 8
Purity of Massoia Lactone
[0086] Fed-batch fermentation was performed in 2 L bioreactors using T3 media. The total fermentation broth was hydrolyzed with H.sub.2SO.sub.4. GCMS analysis of the showed the high production of a single peak of massoia lactone (FIGS. 12A and 12B). This is in contrast to earlier work with Aureobasidium pullalan A-21M, which produced 3-hydroxyl delta-decalactone at ratio of about 1:1.7 [6].
Example 9
Comparison of House-Keeping Genes
[0087] The coding sequences (CDS) of five house-keeping genes of W5-2 strain were identified using known protein sequences of Ustilago maydis as the query to search against the W5-2 whole transcriptome database. SEQ ID NOs:2, 7, 8, 9 and 10 are the CDS sequence for GPD1, Actin, TEF1A, Tubulin1 and RPB1 (RNA polymerase 2, the largest subunit), respectively. There were high variations in the levels of sequence identity to homologs of different Aureobasidium species (Tables 10-14). Note that A. pullulans AY4 has been re-classified as A. melanogenum AY4. For example, GDP1 genomic sequence shares at least 99% identity to homologs of A. melanogenum species at least over 98% of SEQ ID NO:2 while the inter-species homology for GPD1 CDS is below 97% over 98% of SEQ ID NO:2 (Table 10). Similarly, TEFA genomic sequence shares at least 99% identity to homologs of A. melanogenum species over 99% of SEQ ID NO:8 while the inter-species homology for TEF1A CDS is below 98% over 94% of SEQ ID NO:8 (Table 12). RPB1 (SEQ ID NO:10) sequence is the most divergent.
[0088] RPB1 genomic sequence shares at least 96% identity to homologs of A. melanogenum species over 98% of SEQ ID NO:10 while the inter-species homology for RPB1 CDS is below 90% over 92% of SEQ ID NO:10 (Table 14).
TABLE-US-00010 TABLE 10 BLASTn Search Results of GPD1 (SEQ ID NO: 2) Max Total Query E Description score score cover value Ident Accession Aureobasidium melanogenum CBS 1459 1812 98% 0.0 99% AYEN01000011.1 110374 scaffold_4_c3, whole genome shotgun sequence Aureobasidium pullulans AY4 1448 1795 98% 0.0 99% AMCU01000020.1 contig20, whole genome shotgun sequence Aureobasidium namibiae CBS 1371 1692 98% 0.0 97% AYEM01000004.1 147.97 scaffold_2_c1, whole genome shotgun sequence Aureobasidium pullulans isolate 1321 1635 98% 0.0 96% LVWM01000514.1 Santander contig_514, whole genome shotgun sequence Aureobasidium subglaciale EXF- 1315 1636 98% 0.0 96% AYYB01000004.1 2481 scaffold_ 2_c1, whole genome shotgun sequence Aureobasidium pullulans EXF-150 1293 1605 98% 0.0 95% AYEO01000008.1 scaffold_6_c1, whole genome shotgun sequence
TABLE-US-00011 TABLE 11 BLASTn Search Results of Actin (SEQ ID NO: 7) Max Total Query E Description score score cover value Ident Accession Aureobasidium pullulans 1216 2960 99% 0.0 92% AMCU01000120.1 AY4 contig120, whole genome shotgun sequence Aureobasidium melanogenum 1210 2960 99% 0.0 92% AYEN01000004.1 CBS 110374 scaffold_3_c1, whole genome shotgun sequence Aureobasidium namibiae 917 1016 44% 0.0 86% AYEM01000024.1 CBS 147.97 scaffold_18_c1, whole genome shotgun sequence Aureobasidium pullulans 828 1993 96% 0.0 84% LVWM01000225.1 isolate Santander contig_225, whole genome shotgun sequence Aureobasidium pullulans 811 1872 93% 0.0 84% AYEO01000002.1 EXF-150 scaffold_2_c1, whole genome shotgun sequence Aureobasidium subglaciale 614 735 39% 4e-174 82% AYYB01000022.1 EXF-2481 scaffold_19_c1, whole genome shotgun sequence
TABLE-US-00012 TABLE 12 BLASTn Search Results of TEF1A (SEQ ID NO: 8) Max Total Query E Description score score cover value Ident Accession Aureobasidium melanogenum CBS 2041 2472 99% 0.0 99% AYEN01000021.1 110374 scaffold_11_c1, whole genome shotgun sequence Aureobasidium pullulans AY4 2041 2472 99% 0.0 99% AMCU01000064.1 contig64, whole genome shotgun sequence Aureobasidium namibiae CBS 2015 2368 94% 0.0 98% AYEM01000007.1 147.97 scaffold_4_c1, whole genome shotgun sequence Aureobasidium pullulans EXF-150 1881 2112 92% 0.0 96% AYEO01000027.1 scaffold_17_c1, whole genome shotgun sequence Aureobasidium subglaciale EXF- 1753 1985 93% 0.0 94% AYYB01000027.1 2481 scaffold_23_c1, whole genome shotgun sequence
TABLE-US-00013 TABLE 13 BLASTn Search Results of Tubulin1 (SEQ ID NO: 9) Max Total Query E Description score score cover value Ident Accession Aureobasidium melanogenum CBS 110374 1284 2316 97% 0.0 98% AYEN01000040.1 scaffold_23_c2, whole genome shotgun sequence Aureobasidium pullulans AY4 contig32, 1284 2305 97% 0.0 98% AMCU01000032.1 whole genome shotgun sequence Aureobasidium namibiae CBS 147.97 1194 2187 97% 0.0 96% AYEM01000023.1 scaffold_ 17_c1, whole genome shotgun sequence Aureobasidium pullulans isolate Santander 1160 1981 92% 0.0 95% LVWM01000153.1 contig_153, whole genome shotgun sequence Aureobasidium pullulans EXF-150 1158 1984 92% 0.0 95% AYEO01000003.1 scaffold_3_c1, whole genome shotgun sequence Aureobasidium subglaciale EXF-2481 1140 2033 97% 0.0 95% AYYB01000001.1 scaffold_0_c1, whole genome shotgun sequence
TABLE-US-00014 TABLE 14 BLASTn Search Results of RPB1 (SEQ ID NO: 10) Max Total Query E Description score score cover value Ident Accession Aureobasidium melanogenum CBS 110374 7915 9706 98% 0.0 96% AYEN01000002.1 scaffold_1_c2, whole genome shotgun sequence Aureobasidium pullulans AY4 contig81, 7866 9631 99% 0.0 96% AMCU01000081.1 whole genome shotgun sequence Aureobasidium namibiae CBS 147.97 6032 6855 91% 0.0 89% AYEM01000002.1 scaffold_1_c2, whole genome shotgun sequence Aureobasidium subglaciale EXF-2481 5389 6038 91% 0.0 87% AYYB01000017.1 scaffold_15_c1, whole genome shotgun sequence Aureobasidium pullulans contig_319, 5334 5999 92% 0.0 86% LVWM01000319.1 whole genome shotgun sequence Aureobasidium pullulans contig_233, 5334 5999 92% 0.0 86% LVWM01000233.1 whole genome shotgun sequence Aureobasidium pullulans contig_45, whole 5334 5999 92% 0.0 86% LVWM01000045.1 genome shotgun sequence Aureobasidium pullulans EXF-150 5323 5993 92% 0.0 86% AYEO01000028.1 scaffold_18_c1, whole genome shotgun sequence
[0089] The use of the terms "a" and "an" and "the" and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
[0090] Embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
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Sequence CWU
1
1
101666DNAAureobasidium melanogenum strain W5-2misc_feature(36)..(36)n is
a, c, g, or t 1agcgtcccgc caaagcaaca agtagtttta acaacnaagg gttcttggtc
atttagagga 60agtaaaagtc gtaaacaagg cttccgtaag gtgaacctgc ggaaggatca
ttaaagagta 120agggtgctca gcgcccgacc tccaaccctt tgttgttaaa actaccttgt
tgctttggcg 180ggaccgctcg gtctcgagcc gctggggatt cgtcccaggc gagcgcccgc
cagagttaaa 240ccaaactctt gttatttaac cggtcgtctg agttaaaatt ttgaataaat
caaaactttc 300aacaacggat ctcttggttc tcgcatcgat gaagaacgca gcgaaatgcg
ataagtaatg 360tgaattgcag aattcagtga atcatcgaat ctttgaacgc acattgcgcc
ccttggtatt 420ccgaggggca tgcctgttcg agcgtcatta caccactcaa gctatgcttg
gtattgggtg 480ccgtccttag ttgggcgcgc cttaaagacc tcggcgaggc ctcaccggct
ttaggcgtag 540tagaatttat tcgaacgtct gtcaaaggag aggacttctg ccgactgaaa
ccttttattt 600ttctaggttg acctcggatc aggtagggat acccgctgaa cttaagcata
tcaataagcg 660gaggaa
66621014DNAAureobasidium species 2atgcctgtca acgtcggtat
taacggcttc ggtcgcattg gtcgcattgt cttccgcaat 60gccatcgagc tcgacaacgt
ccacgtcgtt gccgtcaacg accccttcat tgagcccgag 120tacgctgcct acatgctcaa
gtacgactcc gtccacggcc agttcaaggg taccattgag 180gtctccggca aggacctgat
cgtcaacggc aagaaggtca ccttctacac cgagagagac 240cccgccaaca tcccctgggc
tgagactggc gcctactacg tcgtcgagtc caccggtgtc 300ttcaccacca ccgagaaggc
ctccgctcac ttgaagggtg gcgccaagaa ggtcgtcatc 360tctgctccct ccgctgacgc
ccccatgttc gtcatgggtg tcaacgagaa gagctacaag 420tccgacatcc aggtcctgtc
caacgcctct tgcaccacca actgccttgc tcccctcgcc 480aaggtcatca acgacaagtt
cggtatcgtt gagggtctca tgaccaccat ccactcctac 540accgccaccc agaagaccgt
cgacggtcct tccggcaagg actggcgcgg tggccgtgct 600gctgcccaga acatcatccc
cagcagcact ggtgccgcca aggctgtcgg caaggtcatt 660cctcagctca acggcaagct
gaccggtatg tccatgcgtg tccccaccgc caacgtctcc 720gttgtcgacc ttactgcccg
tctcgagaag ggtgcctctt acgacaccat caagaaggcc 780atcaaggagg cctccgaggg
tgagcttaag ggcattctcg gctacaccga ggacgacatt 840gtctcctccg acatgtgcgg
tgccaacgag tcctccatct tcgacgccaa ggccggtatc 900tcgctcaacg acaacttcgt
caagcttgtc tcctggtacg acaacgagtg gggttactcc 960cgccgtgtcc tcgacctcct
ggcttacatt gccaaggtcg acggtaacgc ataa 1014319DNAArtificial
Sequenceoligonucleotide primer 3tccgtaggtg aacctgcgg
19420DNAArtificial Sequenceoligonucleotide
primer 4tcctccgctt attgatatgc
20535683DNAAureobasidium pullulans strain BP-1938CDS(506)..(35485)
5cgatggcaac tgttgccaac aaagcggaaa atttctctat gcggaggtgt gttacgaatc
60tgcctaactt ttgcctcatc cactgacgac tgactaatca cagggaggtt agtgttcgct
120gccgagggcg ccatgtcagg cgtcgcccgg cagagttgat catgcaaatt cgaagtgagc
180accgatcaga tgagtcaagt caatatgcat tgtcttatag ccagacgata tgcgcgccac
240aacgattctt gctgacatca cccatataca gtcataagtg tagttcgctt acggagctca
300catgaccgca atgtctatca gagtaagcat gtctgtcgtg gctgacgctg ctctaacaat
360gatgcgtgaa gcatcagtca atcagcaagc gaggaatact tctgccacat tgaccagact
420atcaaccctc tgacatcgag caacagcgac agcaaacgtt tgactacaac aacagccacc
480gtatagcaac attcaacaaa caaag atg tcg cga atg cca cag ggc gca gca
532 Met Ser Arg Met Pro Gln Gly Ala Ala
1 5
aga cgc aac gac tgt gtc tcg gag cac caa ggc act acc gat ctg gag
580Arg Arg Asn Asp Cys Val Ser Glu His Gln Gly Thr Thr Asp Leu Glu
10 15 20 25
gat att gtg cga ttc tgg gaa cga cac tta gac ggt gtg aat gca tct
628Asp Ile Val Arg Phe Trp Glu Arg His Leu Asp Gly Val Asn Ala Ser
30 35 40
gca ttc cct gct ctg tca tct agc ttg gtt gta cct aaa ccc aaa ttg
676Ala Phe Pro Ala Leu Ser Ser Ser Leu Val Val Pro Lys Pro Lys Leu
45 50 55
cag aca gag cat cgc atc agc ctc gga acc gcc gtg tct gat cag tgg
724Gln Thr Glu His Arg Ile Ser Leu Gly Thr Ala Val Ser Asp Gln Trp
60 65 70
tca gat gca gtc atc tgt cga gct gca ctt gct gtc att ttg gcc cgt
772Ser Asp Ala Val Ile Cys Arg Ala Ala Leu Ala Val Ile Leu Ala Arg
75 80 85
tat acg cac gct act gaa gcg ctc tac ggc att gtg gtc gag cag cct
820Tyr Thr His Ala Thr Glu Ala Leu Tyr Gly Ile Val Val Glu Gln Pro
90 95 100 105
tca gtc tcc aat gcc cag aaa cga tcc gcc gat gat gca tcc tcc att
868Ser Val Ser Asn Ala Gln Lys Arg Ser Ala Asp Asp Ala Ser Ser Ile
110 115 120
gtt gta ccg att cgt gtg caa tgt gca tct ggt caa ttt ggg aac gat
916Val Val Pro Ile Arg Val Gln Cys Ala Ser Gly Gln Phe Gly Asn Asp
125 130 135
att ttg gct gca att gct act cac gac gct tct tgt cgt agc ctc agc
964Ile Leu Ala Ala Ile Ala Thr His Asp Ala Ser Cys Arg Ser Leu Ser
140 145 150
gcg atc ggc ctg gat ggc att cgc tgt ctt gat gat gct aaa act gtg
1012Ala Ile Gly Leu Asp Gly Ile Arg Cys Leu Asp Asp Ala Lys Thr Val
155 160 165
gct cgg gga tta cag act gta ttg act gta acc agc agg aag tcg gtg
1060Ala Arg Gly Leu Gln Thr Val Leu Thr Val Thr Ser Arg Lys Ser Val
170 175 180 185
gac gca tca agc cca aac att ctc gac ttg gag aac atc gca tct tct
1108Asp Ala Ser Ser Pro Asn Ile Leu Asp Leu Glu Asn Ile Ala Ser Ser
190 195 200
cac ggt cga gct ctc atg ata gaa tgt caa atg agc acc acc tcg gca
1156His Gly Arg Ala Leu Met Ile Glu Cys Gln Met Ser Thr Thr Ser Ala
205 210 215
tgc ttg cgt gca cag tac gac gcg ggc atc ttg cgt aat gaa cag gta
1204Cys Leu Arg Ala Gln Tyr Asp Ala Gly Ile Leu Arg Asn Glu Gln Val
220 225 230
gtt cgt ctt ctc aaa cag ctc gcg ctt tcg atc cag cac ttt cga ggt
1252Val Arg Leu Leu Lys Gln Leu Ala Leu Ser Ile Gln His Phe Arg Gly
235 240 245
aac gct gcc aac gac ctg cta cgc gac ttc tgc ttt atc tcg cca ggc
1300Asn Ala Ala Asn Asp Leu Leu Arg Asp Phe Cys Phe Ile Ser Pro Gly
250 255 260 265
gaa gag atg gaa att gca tac tgg aat cgt cga agc att cgc aca aat
1348Glu Glu Met Glu Ile Ala Tyr Trp Asn Arg Arg Ser Ile Arg Thr Asn
270 275 280
gag gtt tgt atc cat gat gtg atc ttt aag agg gcg acc tac atg ccg
1396Glu Val Cys Ile His Asp Val Ile Phe Lys Arg Ala Thr Tyr Met Pro
285 290 295
act gat acg gcg gtt tcc gcc tgg gat ggg gag tgg aca tac gca gat
1444Thr Asp Thr Ala Val Ser Ala Trp Asp Gly Glu Trp Thr Tyr Ala Asp
300 305 310
cta gat gtc gta tct tca tgt ctt gcc gat tac gtt cgg tcc ttg gat
1492Leu Asp Val Val Ser Ser Cys Leu Ala Asp Tyr Val Arg Ser Leu Asp
315 320 325
ctg agg tct gga caa gcc ata cca cta tgc ttc gag aag tca aga aac
1540Leu Arg Ser Gly Gln Ala Ile Pro Leu Cys Phe Glu Lys Ser Arg Asn
330 335 340 345
acc atc gcc gct atg gtg gcc gtt ctc aaa gct ggt cat ccg ttt tgc
1588Thr Ile Ala Ala Met Val Ala Val Leu Lys Ala Gly His Pro Phe Cys
350 355 360
ctg att gac ccg tct act cca tct gcg aga atc act cag atg tgc gag
1636Leu Ile Asp Pro Ser Thr Pro Ser Ala Arg Ile Thr Gln Met Cys Glu
365 370 375
cag atg tcc gct acc gtc gct ttc gct tcg aga gca ctt tgt agc atc
1684Gln Met Ser Ala Thr Val Ala Phe Ala Ser Arg Ala Leu Cys Ser Ile
380 385 390
atg caa gca gga gtc tct aga tgt att gca gtt gat gac gat ctc ttt
1732Met Gln Ala Gly Val Ser Arg Cys Ile Ala Val Asp Asp Asp Leu Phe
395 400 405
caa tcc ttg tca tca gtc atc ggg tgt cca cag atg tcc atg acg aga
1780Gln Ser Leu Ser Ser Val Ile Gly Cys Pro Gln Met Ser Met Thr Arg
410 415 420 425
ccc cag gac ctt gcc tat gtc ata ttt aca tcc gga agt act gga atc
1828Pro Gln Asp Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Ile
430 435 440
ccg aag ggc agc atg atc gag cat cga ggt ttt gca agc tgc gca ctt
1876Pro Lys Gly Ser Met Ile Glu His Arg Gly Phe Ala Ser Cys Ala Leu
445 450 455
gaa ttc gga cct caa ttg tta atc gat cgc aac acg cgt gca tta cag
1924Glu Phe Gly Pro Gln Leu Leu Ile Asp Arg Asn Thr Arg Ala Leu Gln
460 465 470
ttc gcc tct cac gct ttt ggc gca tgc ttg tta gag gtt ctg gtg acg
1972Phe Ala Ser His Ala Phe Gly Ala Cys Leu Leu Glu Val Leu Val Thr
475 480 485
ctt atg ctt gga ggt tgt gta tgc gtc ccg tcc gaa aac gat cgc ttg
2020Leu Met Leu Gly Gly Cys Val Cys Val Pro Ser Glu Asn Asp Arg Leu
490 495 500 505
aac aac ctg tca ggt ttc att gaa caa agc ggc gtg aac tgg acc cta
2068Asn Asn Leu Ser Gly Phe Ile Glu Gln Ser Gly Val Asn Trp Thr Leu
510 515 520
ttt acg cct tct ttt att gga gct ctc acg ccc gag act att cgt ggg
2116Phe Thr Pro Ser Phe Ile Gly Ala Leu Thr Pro Glu Thr Ile Arg Gly
525 530 535
gtg cac act gtc gtg ctg ggt gga gag cca atg aca cca ttc atc aga
2164Val His Thr Val Val Leu Gly Gly Glu Pro Met Thr Pro Phe Ile Arg
540 545 550
gac gta tgg gca tca aaa gtg caa ctc ttg tcc ata tat gga caa agt
2212Asp Val Trp Ala Ser Lys Val Gln Leu Leu Ser Ile Tyr Gly Gln Ser
555 560 565
gag agc tcg act gtg tgt agt gtg gtt aaa atc aag cct gat acc acc
2260Glu Ser Ser Thr Val Cys Ser Val Val Lys Ile Lys Pro Asp Thr Thr
570 575 580 585
gat ctg agt agc ctg ggc cac gct ata gga gct cgc ttc tgg atc gtt
2308Asp Leu Ser Ser Leu Gly His Ala Ile Gly Ala Arg Phe Trp Ile Val
590 595 600
gat gct gaa aat ccg agt cga ttg gca cca atc ggc tgc atc ggc gag
2356Asp Ala Glu Asn Pro Ser Arg Leu Ala Pro Ile Gly Cys Ile Gly Glu
605 610 615
ctc atg gta gag agt cct gga att gca cgc gaa tac cta tct gct caa
2404Leu Met Val Glu Ser Pro Gly Ile Ala Arg Glu Tyr Leu Ser Ala Gln
620 625 630
gaa gca cag atg tcc cca ttc ata acg aag aca cct gct tgg tat cct
2452Glu Ala Gln Met Ser Pro Phe Ile Thr Lys Thr Pro Ala Trp Tyr Pro
635 640 645
atg aag cag cgt tgc agt cct gtc aag ttc tac atg acc ggc gat ctt
2500Met Lys Gln Arg Cys Ser Pro Val Lys Phe Tyr Met Thr Gly Asp Leu
650 655 660 665
gct tgt tat gga cgt gat ggc acc gtc atg aat ctt gga cgc aaa gat
2548Ala Cys Tyr Gly Arg Asp Gly Thr Val Met Asn Leu Gly Arg Lys Asp
670 675 680
tcg caa gtc aag atc cga ggc caa cgc gtg gag ctt ggc gat gtg gag
2596Ser Gln Val Lys Ile Arg Gly Gln Arg Val Glu Leu Gly Asp Val Glu
685 690 695
act aat ctg cga tca gtc tta cct aaa cac atc ata cct gtt gtc gag
2644Thr Asn Leu Arg Ser Val Leu Pro Lys His Ile Ile Pro Val Val Glu
700 705 710
gcg att gat tcg atc cat gca tcc gga agc aaa ttt ctg gtt gcg atc
2692Ala Ile Asp Ser Ile His Ala Ser Gly Ser Lys Phe Leu Val Ala Ile
715 720 725
ctg att ggc gca aac cat gga atg aaa aat gaa ttc gat aca gag cca
2740Leu Ile Gly Ala Asn His Gly Met Lys Asn Glu Phe Asp Thr Glu Pro
730 735 740 745
aga cgt gaa gtc tct ata ctg gat gaa acc gcg gtg atc cgt ata agg
2788Arg Arg Glu Val Ser Ile Leu Asp Glu Thr Ala Val Ile Arg Ile Arg
750 755 760
aag agt atg cag gat ctt gtt cca tct tac tgc ata ccc aca cag tat
2836Lys Ser Met Gln Asp Leu Val Pro Ser Tyr Cys Ile Pro Thr Gln Tyr
765 770 775
atc tgc atg gaa cga ctc ctg acc acg aca aca ggg aag gcg gat cgc
2884Ile Cys Met Glu Arg Leu Leu Thr Thr Thr Thr Gly Lys Ala Asp Arg
780 785 790
aag aga cta cgc gcg att tgc gtg gac ctt ctc aag cct tca agg aga
2932Lys Arg Leu Arg Ala Ile Cys Val Asp Leu Leu Lys Pro Ser Arg Arg
795 800 805
gca atg gta cca gaa tct tcg gac ggg ccc acg cta aaa ctc acg gca
2980Ala Met Val Pro Glu Ser Ser Asp Gly Pro Thr Leu Lys Leu Thr Ala
810 815 820 825
gga caa gtt ttg gat gag gca tgg cat cga tac ctg cgt ttt gat tct
3028Gly Gln Val Leu Asp Glu Ala Trp His Arg Tyr Leu Arg Phe Asp Ser
830 835 840
gtt ctc gat ggt tct aag tcg aag ttc ttt gat ctg aat gga gac tcc
3076Val Leu Asp Gly Ser Lys Ser Lys Phe Phe Asp Leu Asn Gly Asp Ser
845 850 855
atc aca gcg atc aag ata gca aat gcg gcg agg aaa cac ggg gta atg
3124Ile Thr Ala Ile Lys Ile Ala Asn Ala Ala Arg Lys His Gly Val Met
860 865 870
ctc aaa gta gca gac att ctt gct aat cct act ctc gcc gac ctg aga
3172Leu Lys Val Ala Asp Ile Leu Ala Asn Pro Thr Leu Ala Asp Leu Arg
875 880 885
gct caa ttt cag att gat ttc aca cct caa aac tcc ata ctt cgc acc
3220Ala Gln Phe Gln Ile Asp Phe Thr Pro Gln Asn Ser Ile Leu Arg Thr
890 895 900 905
tcg tac cgt gga cca atc caa caa tcc ttt gcg caa aac agg ttg tgg
3268Ser Tyr Arg Gly Pro Ile Gln Gln Ser Phe Ala Gln Asn Arg Leu Trp
910 915 920
ttt ctg gac cag ctg aac gtt ggc gcg tca tgg tac ata gta cca gtc
3316Phe Leu Asp Gln Leu Asn Val Gly Ala Ser Trp Tyr Ile Val Pro Val
925 930 935
gcg gtg cgc ttg caa gga aca gtc cat gtc gac gcg ctt gtc acc gca
3364Ala Val Arg Leu Gln Gly Thr Val His Val Asp Ala Leu Val Thr Ala
940 945 950
cta tgt gcc ctg gaa caa cgt cat gaa acg ttg cgt acg acc ttt gaa
3412Leu Cys Ala Leu Glu Gln Arg His Glu Thr Leu Arg Thr Thr Phe Glu
955 960 965
gaa tcc gat ggc gag ggc ata caa cgg att cag cca agt ggg ctt gag
3460Glu Ser Asp Gly Glu Gly Ile Gln Arg Ile Gln Pro Ser Gly Leu Glu
970 975 980 985
cag ctt agg ttg atc gac gtg gat tgc gtg gac tct agg gac tac cag
3508Gln Leu Arg Leu Ile Asp Val Asp Cys Val Asp Ser Arg Asp Tyr Gln
990 995 1000
cga gta ttg gaa gaa gag cag acg act ccc ttc gag ctg agc cgc
3553Arg Val Leu Glu Glu Glu Gln Thr Thr Pro Phe Glu Leu Ser Arg
1005 1010 1015
gag cct gga tgg agg gta gcg ctg ctg cgt ctg gga gat gac gac
3598Glu Pro Gly Trp Arg Val Ala Leu Leu Arg Leu Gly Asp Asp Asp
1020 1025 1030
cac gtc ctc tcc atc gtc atg cat cac atc atc tcc gac ggt tgg
3643His Val Leu Ser Ile Val Met His His Ile Ile Ser Asp Gly Trp
1035 1040 1045
tct gtg gac gtg ctg cgc cac gag cta ggt cag ttc tac tcg gcc
3688Ser Val Asp Val Leu Arg His Glu Leu Gly Gln Phe Tyr Ser Ala
1050 1055 1060
gcg ctc cgg ggg cag gac ccg ttg tcg cag ata agt cct ctg ccg
3733Ala Leu Arg Gly Gln Asp Pro Leu Ser Gln Ile Ser Pro Leu Pro
1065 1070 1075
atc cag tat cgt gac ttc gct ctc tgg cag aga caa gac gag caa
3778Ile Gln Tyr Arg Asp Phe Ala Leu Trp Gln Arg Gln Asp Glu Gln
1080 1085 1090
gtt gcg gag cat cag cgc cag ctg gag cat tgg aca gag cag ttg
3823Val Ala Glu His Gln Arg Gln Leu Glu His Trp Thr Glu Gln Leu
1095 1100 1105
gca gac agt tca ccc gcc gag ttg ttg agc gac cac ccg agg cca
3868Ala Asp Ser Ser Pro Ala Glu Leu Leu Ser Asp His Pro Arg Pro
1110 1115 1120
tcg att ctt tct ggc cag gcg ggc gct att ccc gtc aat gtt caa
3913Ser Ile Leu Ser Gly Gln Ala Gly Ala Ile Pro Val Asn Val Gln
1125 1130 1135
ggc tct ctg tat cag gcg ctt cgg gcg ttc tgc cgc gct cac cag
3958Gly Ser Leu Tyr Gln Ala Leu Arg Ala Phe Cys Arg Ala His Gln
1140 1145 1150
gtc acc tct ttc gta gtc ctg ctc acg gcg ttc cgc ata gca cac
4003Val Thr Ser Phe Val Val Leu Leu Thr Ala Phe Arg Ile Ala His
1155 1160 1165
tat cgt ctg acg ggt gcg gag gac gca acc att gga act ccc att
4048Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro Ile
1170 1175 1180
gca aat cgc aac cgg cca gag ctc gag aac atg atc ggt ttc ttc
4093Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Phe Phe
1185 1190 1195
gtc aat aca caa tgc atg cgc atc gtc att ggc agt gac gac aca
4138Val Asn Thr Gln Cys Met Arg Ile Val Ile Gly Ser Asp Asp Thr
1200 1205 1210
ttt gaa ggg ctg gtg cag caa gta cgc tcg ata act gca gct gcc
4183Phe Glu Gly Leu Val Gln Gln Val Arg Ser Ile Thr Ala Ala Ala
1215 1220 1225
cac gag aac cag gac gtt cca ttc gag cgc atc gtg tca gca ctg
4228His Glu Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ala Leu
1230 1235 1240
ctt ccc ggt tct aga gac aca tca cgc aat cct ctg gtt cag ctc
4273Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu
1245 1250 1255
atg ttt gct gtc cac tcg caa aga aac ctt ggt cag atc agt cta
4318Met Phe Ala Val His Ser Gln Arg Asn Leu Gly Gln Ile Ser Leu
1260 1265 1270
gaa ggc ctg cag ggt gaa ttg ctg gga gtg gca tcg cca acg aga
4363Glu Gly Leu Gln Gly Glu Leu Leu Gly Val Ala Ser Pro Thr Arg
1275 1280 1285
ttc gat gta gag ttc cac ctc ttc caa gag gag aat atg cta agc
4408Phe Asp Val Glu Phe His Leu Phe Gln Glu Glu Asn Met Leu Ser
1290 1295 1300
gga agg gtg ctg ttt tca gac gat ctt ttc gag cag aag act atg
4453Gly Arg Val Leu Phe Ser Asp Asp Leu Phe Glu Gln Lys Thr Met
1305 1310 1315
caa ggc atg gtc gac gtg ttc cag gaa gtg ctc agc cgg ggc ctt
4498Gln Gly Met Val Asp Val Phe Gln Glu Val Leu Ser Arg Gly Leu
1320 1325 1330
gag cag ccc cag ata cct ctg gcg acc ctc ccg ctc acg cac gga
4543Glu Gln Pro Gln Ile Pro Leu Ala Thr Leu Pro Leu Thr His Gly
1335 1340 1345
ctg gag gag ctc agg acc atg ggt ctt ctc gac gtg gag aag aca
4588Leu Glu Glu Leu Arg Thr Met Gly Leu Leu Asp Val Glu Lys Thr
1350 1355 1360
gac tac cct cga gag tcg agc gtg gtg gac gtg ttc cgt gag caa
4633Asp Tyr Pro Arg Glu Ser Ser Val Val Asp Val Phe Arg Glu Gln
1365 1370 1375
gcg gct gcc tgc tcc gag gcg att gcg gtc aaa gac tcg tcg gcg
4678Ala Ala Ala Cys Ser Glu Ala Ile Ala Val Lys Asp Ser Ser Ala
1380 1385 1390
cag ctc acc tac tcg gag ctc gat cga cag tcg gac gag ctt gcc
4723Gln Leu Thr Tyr Ser Glu Leu Asp Arg Gln Ser Asp Glu Leu Ala
1395 1400 1405
ggc tgg ctg cgc cag caa cgt ctt cct gcg gag tcg ttg gtt gca
4768Gly Trp Leu Arg Gln Gln Arg Leu Pro Ala Glu Ser Leu Val Ala
1410 1415 1420
gtg ctg gca ccc agg tcg tgc cag acc att gtc gcg ttc ctg ggc
4813Val Leu Ala Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly
1425 1430 1435
atc ctc aag gcg aat ctg gca tac ctg ccg cta gac gtc aac gtg
4858Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val
1440 1445 1450
ccc gct act cgc ctc gag tcg ata ctg tct gcc gtc ggc ggc cgg
4903Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser Ala Val Gly Gly Arg
1455 1460 1465
aag ctg gtc ttg ctt gga gct gac gtg gcc gac cct ggc ctt cgc
4948Lys Leu Val Leu Leu Gly Ala Asp Val Ala Asp Pro Gly Leu Arg
1470 1475 1480
ctg gcg gat gtg gag ctc gtg cgg atc ggc gac aca ctc ggc cgc
4993Leu Ala Asp Val Glu Leu Val Arg Ile Gly Asp Thr Leu Gly Arg
1485 1490 1495
tgt gta ccc ggg gcg ccc ggc gac aac gag gca cct gtg gtg cag
5038Cys Val Pro Gly Ala Pro Gly Asp Asn Glu Ala Pro Val Val Gln
1500 1505 1510
cct tct gcc aca agc ctt gcc tac gtc atc ttc act tcc ggc tcg
5083Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser
1515 1520 1525
acc ggc aag ccg aag ggt gtc atg gtc gag cac cgg ggt gta gtg
5128Thr Gly Lys Pro Lys Gly Val Met Val Glu His Arg Gly Val Val
1530 1535 1540
cga ctt gtc aag cag agc aat gtt gtc tac cat ctc ccg tcc aca
5173Arg Leu Val Lys Gln Ser Asn Val Val Tyr His Leu Pro Ser Thr
1545 1550 1555
tct cgc gtg gcc cac ctg tcg aat ctc gcc ttt gat gcc tcg gcg
5218Ser Arg Val Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ser Ala
1560 1565 1570
tgg gag atc tat gcg gca ctg ctt aat ggc ggt aca ctc atc tgc
5263Trp Glu Ile Tyr Ala Ala Leu Leu Asn Gly Gly Thr Leu Ile Cys
1575 1580 1585
att gac tat ttc aca act cta gac tgc tct gct ctc ggc gcc aaa
5308Ile Asp Tyr Phe Thr Thr Leu Asp Cys Ser Ala Leu Gly Ala Lys
1590 1595 1600
ttc atc aag gag aag atc gtc gcg acc atg att ccg cca gcg ctt
5353Phe Ile Lys Glu Lys Ile Val Ala Thr Met Ile Pro Pro Ala Leu
1605 1610 1615
ctg aag caa tgt ctg gcg atc ttc ccg acc gct ctt agt gaa ctg
5398Leu Lys Gln Cys Leu Ala Ile Phe Pro Thr Ala Leu Ser Glu Leu
1620 1625 1630
gtc ctg ctg ttt gct gcc gga gat cga ttc agc agt ggc gat gcc
5443Val Leu Leu Phe Ala Ala Gly Asp Arg Phe Ser Ser Gly Asp Ala
1635 1640 1645
gtc gaa gtg cag cgc cac acc aaa ggc gct gtt tgt aac gcg tac
5488Val Glu Val Gln Arg His Thr Lys Gly Ala Val Cys Asn Ala Tyr
1650 1655 1660
gga ccg aca gaa aac acc att ctt agt acg atc tac gaa gtc aag
5533Gly Pro Thr Glu Asn Thr Ile Leu Ser Thr Ile Tyr Glu Val Lys
1665 1670 1675
cag aat gag aac ttc ccg aac ggt gtg cct atc ggc cgc gct gtg
5578Gln Asn Glu Asn Phe Pro Asn Gly Val Pro Ile Gly Arg Ala Val
1680 1685 1690
agc aac tca ggg gca tat gtc atg gac ccg cag cag caa ctg gtg
5623Ser Asn Ser Gly Ala Tyr Val Met Asp Pro Gln Gln Gln Leu Val
1695 1700 1705
cct ctc ggg gtg atg ggc gag ctc gtc gtc acc ggc gac ggc ctg
5668Pro Leu Gly Val Met Gly Glu Leu Val Val Thr Gly Asp Gly Leu
1710 1715 1720
gcc cgt ggt tac acc gac ccg tca ctg gat gcg gac cgc ttt gtg
5713Ala Arg Gly Tyr Thr Asp Pro Ser Leu Asp Ala Asp Arg Phe Val
1725 1730 1735
cag gtc tcc gtc aac ggg cag ctc gtg aga gcg tac cga aca ggc
5758Gln Val Ser Val Asn Gly Gln Leu Val Arg Ala Tyr Arg Thr Gly
1740 1745 1750
gat cgc gtg cgc tgc agg cct tgc gat ggc cag atc gag ttc ttt
5803Asp Arg Val Arg Cys Arg Pro Cys Asp Gly Gln Ile Glu Phe Phe
1755 1760 1765
gga cgt atg gac cgg caa gtc aag atc cga gga cat cgc atc gag
5848Gly Arg Met Asp Arg Gln Val Lys Ile Arg Gly His Arg Ile Glu
1770 1775 1780
ctc gca gag gta gag cat gcg gtg ctt ggc ttg gaa gac gtg caa
5893Leu Ala Glu Val Glu His Ala Val Leu Gly Leu Glu Asp Val Gln
1785 1790 1795
gac gct gcc gtt atc gca ttt gac aat gtg gac agc gaa gag cca
5938Asp Ala Ala Val Ile Ala Phe Asp Asn Val Asp Ser Glu Glu Pro
1800 1805 1810
gaa atg gtt ggg ttt gtc act att acc gaa gac aat cct gtc cgt
5983Glu Met Val Gly Phe Val Thr Ile Thr Glu Asp Asn Pro Val Arg
1815 1820 1825
gag gac gaa acc agc ggt caa gta gaa gac tgg gcg aac cac ttc
6028Glu Asp Glu Thr Ser Gly Gln Val Glu Asp Trp Ala Asn His Phe
1830 1835 1840
gag ata agt acc tac acc gat atc gcg gcg atc gat cag ggt agc
6073Glu Ile Ser Thr Tyr Thr Asp Ile Ala Ala Ile Asp Gln Gly Ser
1845 1850 1855
att gga agt gac ttt gta ggt tgg act tct atg tac gac gga agc
6118Ile Gly Ser Asp Phe Val Gly Trp Thr Ser Met Tyr Asp Gly Ser
1860 1865 1870
gag atc gac aag gca gag atg caa gaa tgg ctt gcc gat acc atg
6163Glu Ile Asp Lys Ala Glu Met Gln Glu Trp Leu Ala Asp Thr Met
1875 1880 1885
gcc tct atg ctc gac ggg cag gcg ccg ggc aat gtg tta gag ata
6208Ala Ser Met Leu Asp Gly Gln Ala Pro Gly Asn Val Leu Glu Ile
1890 1895 1900
ggt aca ggc act ggc atg gtc ctc ttc aat ctc ggc gac gga ctg
6253Gly Thr Gly Thr Gly Met Val Leu Phe Asn Leu Gly Asp Gly Leu
1905 1910 1915
cag agc tat gtc ggc ctc gaa cca tca aga tcg gcg gcc gct ttt
6298Gln Ser Tyr Val Gly Leu Glu Pro Ser Arg Ser Ala Ala Ala Phe
1920 1925 1930
gtc aac cag acg att aag tcg ctc ccc acc ctt gct ggc aac gct
6343Val Asn Gln Thr Ile Lys Ser Leu Pro Thr Leu Ala Gly Asn Ala
1935 1940 1945
gaa gta cac att ggc act gcg acc gac gtg gcc cgt cta gat ggc
6388Glu Val His Ile Gly Thr Ala Thr Asp Val Ala Arg Leu Asp Gly
1950 1955 1960
ctc cgc ccc gac tta gtg gta gtc aat tcg gta gtc cag tac ttc
6433Leu Arg Pro Asp Leu Val Val Val Asn Ser Val Val Gln Tyr Phe
1965 1970 1975
cca tca cca gag tac cta atg gaa gtc gtg gag gct ctt gca cgt
6478Pro Ser Pro Glu Tyr Leu Met Glu Val Val Glu Ala Leu Ala Arg
1980 1985 1990
ctg ccg ggc gtc gag cga att ttc ttc gga gac gta cgt tcg tac
6523Leu Pro Gly Val Glu Arg Ile Phe Phe Gly Asp Val Arg Ser Tyr
1995 2000 2005
gcc atc aac aga gat ttc ctg gct gcc aga gct cta cac gaa ctt
6568Ala Ile Asn Arg Asp Phe Leu Ala Ala Arg Ala Leu His Glu Leu
2010 2015 2020
ggc gac aga gcg act aag cac gag att cgg cga aag atg cta gag
6613Gly Asp Arg Ala Thr Lys His Glu Ile Arg Arg Lys Met Leu Glu
2025 2030 2035
atg gaa gaa cgc gaa gag gag ctg ctc gtc gac cca gct ttc ttc
6658Met Glu Glu Arg Glu Glu Glu Leu Leu Val Asp Pro Ala Phe Phe
2040 2045 2050
acc atg ttg acc agc agt ctc cct ggc ctg att cag cat gtc gag
6703Thr Met Leu Thr Ser Ser Leu Pro Gly Leu Ile Gln His Val Glu
2055 2060 2065
atc ttg ccg aag ctg atg aga gcc act aat gag ctc agc gcg tat
6748Ile Leu Pro Lys Leu Met Arg Ala Thr Asn Glu Leu Ser Ala Tyr
2070 2075 2080
cga tac act gct gta gta cac gtg tgc cgt gcc ggt caa gag cct
6793Arg Tyr Thr Ala Val Val His Val Cys Arg Ala Gly Gln Glu Pro
2085 2090 2095
cgt tcc gtg cat acg atc gac gac gat gcc tgg gtg aat ctt gga
6838Arg Ser Val His Thr Ile Asp Asp Asp Ala Trp Val Asn Leu Gly
2100 2105 2110
gct tct cgg ttg agt cgc cct acc ctt tca agc ctt ttg caa act
6883Ala Ser Arg Leu Ser Arg Pro Thr Leu Ser Ser Leu Leu Gln Thr
2115 2120 2125
tcc gag ggc gca tcg gcc gtc gca gta agc aat att cct tac agc
6928Ser Glu Gly Ala Ser Ala Val Ala Val Ser Asn Ile Pro Tyr Ser
2130 2135 2140
aag acc atc aca gag cga gcg ctc gtt agt gcg ctc gat gag gat
6973Lys Thr Ile Thr Glu Arg Ala Leu Val Ser Ala Leu Asp Glu Asp
2145 2150 2155
gat atg caa gac tca tcg gac tgg ctg ctg gcc gtg cgc gag aca
7018Asp Met Gln Asp Ser Ser Asp Trp Leu Leu Ala Val Arg Glu Thr
2160 2165 2170
ggc aga tct tgt tcc tcc ttc tcc gca aca gac ctt gtc gag ctt
7063Gly Arg Ser Cys Ser Ser Phe Ser Ala Thr Asp Leu Val Glu Leu
2175 2180 2185
gct cga gag acg ggc tgg cgt gtg gag ctc agc tgg gca cga cag
7108Ala Arg Glu Thr Gly Trp Arg Val Glu Leu Ser Trp Ala Arg Gln
2190 2195 2200
tac tca cag aaa ggc gca ctc gat gct gtc ttc cac aga cac cct
7153Tyr Ser Gln Lys Gly Ala Leu Asp Ala Val Phe His Arg His Pro
2205 2210 2215
gtt tcc gct ggg agc ggg cgt gtc atg ttc cag ttt cca gtt gag
7198Val Ser Ala Gly Ser Gly Arg Val Met Phe Gln Phe Pro Val Glu
2220 2225 2230
acc gaa gat cga ccg cac atc tca cgc acg aac cga cct tta cag
7243Thr Glu Asp Arg Pro His Ile Ser Arg Thr Asn Arg Pro Leu Gln
2235 2240 2245
cga ttg cag aag aag cga acc gag aca cat gtt cat gag cag ttg
7288Arg Leu Gln Lys Lys Arg Thr Glu Thr His Val His Glu Gln Leu
2250 2255 2260
cgg gct ttg ctt cca cga tac atg gtt cct acg cgg att gtg gcg
7333Arg Ala Leu Leu Pro Arg Tyr Met Val Pro Thr Arg Ile Val Ala
2265 2270 2275
ctt gat aag ctg ccc gtc aat gca aac ggc aag gtt gat cgt caa
7378Leu Asp Lys Leu Pro Val Asn Ala Asn Gly Lys Val Asp Arg Gln
2280 2285 2290
cag ctc gct agg aca gcc cag gtt ctc cca gcg agc aag gcg ccg
7423Gln Leu Ala Arg Thr Ala Gln Val Leu Pro Ala Ser Lys Ala Pro
2295 2300 2305
tct gca tgc gtg gcc cca cgc aac gaa ttg gaa atg aca ctg tgt
7468Ser Ala Cys Val Ala Pro Arg Asn Glu Leu Glu Met Thr Leu Cys
2310 2315 2320
gaa gag ttc tcg cag gtt ctt ggc gtc gag gtc ggc att act gac
7513Glu Glu Phe Ser Gln Val Leu Gly Val Glu Val Gly Ile Thr Asp
2325 2330 2335
aat ttc ttc cac ctg ggt ggc cac tct ctc atg gca aca aag ttc
7558Asn Phe Phe His Leu Gly Gly His Ser Leu Met Ala Thr Lys Phe
2340 2345 2350
gcc gct cgt atc agc cgc cgg ctg aat gct atc gtt tcg gtc aag
7603Ala Ala Arg Ile Ser Arg Arg Leu Asn Ala Ile Val Ser Val Lys
2355 2360 2365
aat gtc ttc gac cac ccc gta cct atg gat ctt gca gcg aca atc
7648Asn Val Phe Asp His Pro Val Pro Met Asp Leu Ala Ala Thr Ile
2370 2375 2380
caa gaa ggc tca aag ctt cat act cca atc cct cgc acg gct tac
7693Gln Glu Gly Ser Lys Leu His Thr Pro Ile Pro Arg Thr Ala Tyr
2385 2390 2395
agc ggt cct gtc gaa cag tct ttc gca caa gga cgt ctt tgg ttc
7738Ser Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp Phe
2400 2405 2410
ctt gac caa ttc aat cct agc tcg att ggg tat gtg atg cct ttc
7783Leu Asp Gln Phe Asn Pro Ser Ser Ile Gly Tyr Val Met Pro Phe
2415 2420 2425
gct gcg cgt ctt cat ggt caa cta caa atc gaa gcg ctc aca gca
7828Ala Ala Arg Leu His Gly Gln Leu Gln Ile Glu Ala Leu Thr Ala
2430 2435 2440
gca ttg ttc gct ttg gaa cag cga cat gag atc ctg cga aca acg
7873Ala Leu Phe Ala Leu Glu Gln Arg His Glu Ile Leu Arg Thr Thr
2445 2450 2455
ttg gac gca cac gat ggt gta ggc atg cag atc gtt cac gcg gaa
7918Leu Asp Ala His Asp Gly Val Gly Met Gln Ile Val His Ala Glu
2460 2465 2470
cat ccg caa cag ttg aga atc att gat gtg tca gca aag gcg tcg
7963His Pro Gln Gln Leu Arg Ile Ile Asp Val Ser Ala Lys Ala Ser
2475 2480 2485
agc agt tat gct cag aca ctg cgt gac gag cag gcg tca cct ttc
8008Ser Ser Tyr Ala Gln Thr Leu Arg Asp Glu Gln Ala Ser Pro Phe
2490 2495 2500
gac cta agc aag gaa cca ggt tgg aga gtc tcg ttg ctg cag ctc
8053Asp Leu Ser Lys Glu Pro Gly Trp Arg Val Ser Leu Leu Gln Leu
2505 2510 2515
agt gag ata gat tat gtt ctt tcc att gta atg cat cac acc atc
8098Ser Glu Ile Asp Tyr Val Leu Ser Ile Val Met His His Thr Ile
2520 2525 2530
tat gac ggt tgg tct ctc gac gta ctc cgg cgg gag cta agt cag
8143Tyr Asp Gly Trp Ser Leu Asp Val Leu Arg Arg Glu Leu Ser Gln
2535 2540 2545
ttt tat gcc gct gcc atc cgt ggt cga gaa cct cta tcg aca atc
8188Phe Tyr Ala Ala Ala Ile Arg Gly Arg Glu Pro Leu Ser Thr Ile
2550 2555 2560
gag cca ttg cct atc caa tac cgc gac ttt tct gtc tgg caa aag
8233Glu Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Val Trp Gln Lys
2565 2570 2575
cag gaa gac caa gtc gca gag cat cga cga cag ctc cat tat tgg
8278Gln Glu Asp Gln Val Ala Glu His Arg Arg Gln Leu His Tyr Trp
2580 2585 2590
ata gag cag cta gat ggc agc tct cct gct gag ttc cta aac gat
8323Ile Glu Gln Leu Asp Gly Ser Ser Pro Ala Glu Phe Leu Asn Asp
2595 2600 2605
aaa cca cgg cct acg ttg ctt tct ggc aag gca gga gtt gtg gaa
8368Lys Pro Arg Pro Thr Leu Leu Ser Gly Lys Ala Gly Val Val Glu
2610 2615 2620
att gct gtg aag ggc act gta tat caa cgt ctg cta gag ttc tgc
8413Ile Ala Val Lys Gly Thr Val Tyr Gln Arg Leu Leu Glu Phe Cys
2625 2630 2635
agg ctt cat cag gtc acc tcg ttc atg gtg ctg ctt gcg gca ttc
8458Arg Leu His Gln Val Thr Ser Phe Met Val Leu Leu Ala Ala Phe
2640 2645 2650
cga gcg aca cac tat cgt ctg aca ggc aca gag gac gcg act gtc
8503Arg Ala Thr His Tyr Arg Leu Thr Gly Thr Glu Asp Ala Thr Val
2655 2660 2665
gga aca ccc atc gcc aat cgc aat cga cct gag ctg gag aac atg
8548Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Met
2670 2675 2680
att gga ttg ttc gtg aat act cag tgt ata cgc ctc aag atc gag
8593Ile Gly Leu Phe Val Asn Thr Gln Cys Ile Arg Leu Lys Ile Glu
2685 2690 2695
gac aat gat act ctc gag gag cta gta cag cac gtt cgt gcc acg
8638Asp Asn Asp Thr Leu Glu Glu Leu Val Gln His Val Arg Ala Thr
2700 2705 2710
atc aca gca tca atc tcg aac cag gat gta ccc ttt gaa cag gta
8683Ile Thr Ala Ser Ile Ser Asn Gln Asp Val Pro Phe Glu Gln Val
2715 2720 2725
gtg tct gca ttg cta cca gga tca cgc gac acc tct agg aac cca
8728Val Ser Ala Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn Pro
2730 2735 2740
cta gtt cag ctg act ttt gcg gtg cat tct cag cga aat ttg gct
8773Leu Val Gln Leu Thr Phe Ala Val His Ser Gln Arg Asn Leu Ala
2745 2750 2755
gac att cag cta gaa aac gtg gag acc aat gct atg cca att tgc
8818Asp Ile Gln Leu Glu Asn Val Glu Thr Asn Ala Met Pro Ile Cys
2760 2765 2770
ccc tcg aca cgt ttc gac gct gaa ttc cac ctc ttc caa gag gag
8863Pro Ser Thr Arg Phe Asp Ala Glu Phe His Leu Phe Gln Glu Glu
2775 2780 2785
aat atg cta agc gga agg gtg ctg ttt tca gac gat ctt ttc gag
8908Asn Met Leu Ser Gly Arg Val Leu Phe Ser Asp Asp Leu Phe Glu
2790 2795 2800
cag aag act atg caa ggc atg gtc gac gtg ttc cag gaa gtg ctc
8953Gln Lys Thr Met Gln Gly Met Val Asp Val Phe Gln Glu Val Leu
2805 2810 2815
agc cgg ggc ctt gag cag ccc cag ata cct ctg gcg acc ctc ccg
8998Ser Arg Gly Leu Glu Gln Pro Gln Ile Pro Leu Ala Thr Leu Pro
2820 2825 2830
ctc acg cac gga ctg gag gag ctc agg acc atg ggt ctt ctc gac
9043Leu Thr His Gly Leu Glu Glu Leu Arg Thr Met Gly Leu Leu Asp
2835 2840 2845
gtg gag aag aca gac tac cct cga gag tcg agc gtg gtg gac gtg
9088Val Glu Lys Thr Asp Tyr Pro Arg Glu Ser Ser Val Val Asp Val
2850 2855 2860
ttc cgt gag caa gcg gct gcc tgc tcc gag gcg att gcg gtc aaa
9133Phe Arg Glu Gln Ala Ala Ala Cys Ser Glu Ala Ile Ala Val Lys
2865 2870 2875
gac tcg tcg gcg cag ctc acc tac tcg gag ctc gat cga cag tcg
9178Asp Ser Ser Ala Gln Leu Thr Tyr Ser Glu Leu Asp Arg Gln Ser
2880 2885 2890
gac gag ctt gcc ggc tgg ctg cgc cag caa cgt ctt cct gcg gag
9223Asp Glu Leu Ala Gly Trp Leu Arg Gln Gln Arg Leu Pro Ala Glu
2895 2900 2905
tcg ttg gtt gca gtg ctg gca ccc agg tcg tgc cag acc att gtc
9268Ser Leu Val Ala Val Leu Ala Pro Arg Ser Cys Gln Thr Ile Val
2910 2915 2920
gcg ttc ctg ggc atc ctc aag gcg aat ctg gca tac ctg ccg cta
9313Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu
2925 2930 2935
gac gtc aac gtg ccc gct act cgc ctc gag tcg ata ctg tct gcc
9358Asp Val Asn Val Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser Ala
2940 2945 2950
gtc ggc ggc cgg aag ctg gtc ttg ctt gga gct gac gtg gcc gac
9403Val Gly Gly Arg Lys Leu Val Leu Leu Gly Ala Asp Val Ala Asp
2955 2960 2965
cct ggc ctt cgc ctg gcg gat gtg gag ctc gtg cgg atc ggc gac
9448Pro Gly Leu Arg Leu Ala Asp Val Glu Leu Val Arg Ile Gly Asp
2970 2975 2980
aca ctc ggc cgc tgt gta ccc ggg gcg ccc ggc gac aat gag gca
9493Thr Leu Gly Arg Cys Val Pro Gly Ala Pro Gly Asp Asn Glu Ala
2985 2990 2995
cct gtg gtg cag cct tct gcc aca agc ctt gcc tac gtc atc ttc
9538Pro Val Val Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe
3000 3005 3010
act tcc ggc tcg acc ggc aag ccg aag ggt gtc atg gtc gag cac
9583Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Val Glu His
3015 3020 3025
cgt agt atc gtc cgc ttg atg agg cac agc aat gtc tcg agt cgc
9628Arg Ser Ile Val Arg Leu Met Arg His Ser Asn Val Ser Ser Arg
3030 3035 3040
ctt ctg cta cat ccc cgc atg acc cac ctg tcg aat ctc gcc ttc
9673Leu Leu Leu His Pro Arg Met Thr His Leu Ser Asn Leu Ala Phe
3045 3050 3055
gat gcg tcg gtg tgg gag att ttc ttg acg ctg ctc aac ggt gga
9718Asp Ala Ser Val Trp Glu Ile Phe Leu Thr Leu Leu Asn Gly Gly
3060 3065 3070
aca ttg att tgt att gac tac ctc tcg tca cta gac tgt cgt gct
9763Thr Leu Ile Cys Ile Asp Tyr Leu Ser Ser Leu Asp Cys Arg Ala
3075 3080 3085
ctt ggg gta agt atc ctg gaa cac cag gtt gac gca tcg gta ctt
9808Leu Gly Val Ser Ile Leu Glu His Gln Val Asp Ala Ser Val Leu
3090 3095 3100
cct cct gct ttg ctc aaa caa tgc cta gca aat gtc cct gag gca
9853Pro Pro Ala Leu Leu Lys Gln Cys Leu Ala Asn Val Pro Glu Ala
3105 3110 3115
ctt gcg agc ctg caa gtg ctc ttg tcc gct gga gat cga ctc gac
9898Leu Ala Ser Leu Gln Val Leu Leu Ser Ala Gly Asp Arg Leu Asp
3120 3125 3130
agt cgt gat gct ata gag agt tgc gca ctc gtg cgc gga agt gtc
9943Ser Arg Asp Ala Ile Glu Ser Cys Ala Leu Val Arg Gly Ser Val
3135 3140 3145
tac aat ggg tat ggt ccc acg gag aat ggc atc cag agc aca atc
9988Tyr Asn Gly Tyr Gly Pro Thr Glu Asn Gly Ile Gln Ser Thr Ile
3150 3155 3160
tat gaa gtc aaa gcg gac gct gag ttt gtc aat ggt gtg cct atc
10033Tyr Glu Val Lys Ala Asp Ala Glu Phe Val Asn Gly Val Pro Ile
3165 3170 3175
ggc cgc gct gtg agc aac tca ggg gca tat gtc atg gac ccg cag
10078Gly Arg Ala Val Ser Asn Ser Gly Ala Tyr Val Met Asp Pro Gln
3180 3185 3190
cag caa ctg gtg cct ctc ggg gtg atg ggc gag ctc gtc gtc acc
10123Gln Gln Leu Val Pro Leu Gly Val Met Gly Glu Leu Val Val Thr
3195 3200 3205
ggc gac ggc ctg gcc cgt ggt tac acc gac ccg tca ctg gat gcg
10168Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Ser Leu Asp Ala
3210 3215 3220
gac cgc ttt gtg cag gtc tcc gtc aac ggg cag ctc gtg aga gcg
10213Asp Arg Phe Val Gln Val Ser Val Asn Gly Gln Leu Val Arg Ala
3225 3230 3235
tac cga aca ggc gat cgc gtg cgc tgc agg cct tgc gat ggc cag
10258Tyr Arg Thr Gly Asp Arg Val Arg Cys Arg Pro Cys Asp Gly Gln
3240 3245 3250
atc gag ttc ttt gga cgt atg gac cgg caa gtc aag atc cga gga
10303Ile Glu Phe Phe Gly Arg Met Asp Arg Gln Val Lys Ile Arg Gly
3255 3260 3265
cat cgc atc gag ctc gca gag gta gag cat gcg gtg ctt ggc ttg
10348His Arg Ile Glu Leu Ala Glu Val Glu His Ala Val Leu Gly Leu
3270 3275 3280
gaa gac gtg caa gac gct gcc gtt ctc ata gct caa aca gcc gaa
10393Glu Asp Val Gln Asp Ala Ala Val Leu Ile Ala Gln Thr Ala Glu
3285 3290 3295
aat gaa gag cta gtt ggc ttc ttc acg ctt cga caa acc cag gct
10438Asn Glu Glu Leu Val Gly Phe Phe Thr Leu Arg Gln Thr Gln Ala
3300 3305 3310
gtg cag tca aat ggt gcc gct ggt gtt gtg cca gag cac agc gac
10483Val Gln Ser Asn Gly Ala Ala Gly Val Val Pro Glu His Ser Asp
3315 3320 3325
tcc gag ctg gcg caa tcc tgc tct tgc act caa acg gag cgt cga
10528Ser Glu Leu Ala Gln Ser Cys Ser Cys Thr Gln Thr Glu Arg Arg
3330 3335 3340
gtc cgc aac aga ttg caa tcc tgt ctt cct cgc tac atg gtt ccg
10573Val Arg Asn Arg Leu Gln Ser Cys Leu Pro Arg Tyr Met Val Pro
3345 3350 3355
tcg cga atg gtc ctt ttg gat cga ctg cct gtc aac ccc aat ggt
10618Ser Arg Met Val Leu Leu Asp Arg Leu Pro Val Asn Pro Asn Gly
3360 3365 3370
aaa gtt gat cga caa gag ctc acg agg cgc gct cag gat ctc cca
10663Lys Val Asp Arg Gln Glu Leu Thr Arg Arg Ala Gln Asp Leu Pro
3375 3380 3385
ata agc gag tca tcc cca gtg cac gtc aaa ccg cgt act gaa ctg
10708Ile Ser Glu Ser Ser Pro Val His Val Lys Pro Arg Thr Glu Leu
3390 3395 3400
gaa agg tcg ctg tgc gag gag ttc gcc gat gtt ata ggt ttg gaa
10753Glu Arg Ser Leu Cys Glu Glu Phe Ala Asp Val Ile Gly Leu Glu
3405 3410 3415
gtc ggc gtt acc gat aat ttc ttc gac cta ggc ggg cac tct ctc
10798Val Gly Val Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu
3420 3425 3430
atg gcg atg aaa ctc gca gct cgc atc agc cgt cgt tcg aat gca
10843Met Ala Met Lys Leu Ala Ala Arg Ile Ser Arg Arg Ser Asn Ala
3435 3440 3445
cat ata tca gtc aag gac att ttc gac cac ccg ctg att gca gat
10888His Ile Ser Val Lys Asp Ile Phe Asp His Pro Leu Ile Ala Asp
3450 3455 3460
ctc gca atg aaa att cgg gaa ggc tcc gat ctg cac act cca att
10933Leu Ala Met Lys Ile Arg Glu Gly Ser Asp Leu His Thr Pro Ile
3465 3470 3475
ccc cac agg atg tac gtt gga cct atc cag cta tca ttc gca cag
10978Pro His Arg Met Tyr Val Gly Pro Ile Gln Leu Ser Phe Ala Gln
3480 3485 3490
gga cgc ttg tgg ttc ctc gac caa ttg aat ttg ggc gca tcg tgg
11023Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Leu Gly Ala Ser Trp
3495 3500 3505
tac gtc atg cca ctt gct atg cgc ctc caa ggc tcg ctc cag ctc
11068Tyr Val Met Pro Leu Ala Met Arg Leu Gln Gly Ser Leu Gln Leu
3510 3515 3520
gac gcg tta gag act gca ctg ttt gct atc gag cag cga cac gaa
11113Asp Ala Leu Glu Thr Ala Leu Phe Ala Ile Glu Gln Arg His Glu
3525 3530 3535
acc tta cgg atg aca ttt gca gaa caa gac gga gta gct gta caa
11158Thr Leu Arg Met Thr Phe Ala Glu Gln Asp Gly Val Ala Val Gln
3540 3545 3550
gta gtg cat gca gcc cac tac aaa cac atc aag atg atc gac aaa
11203Val Val His Ala Ala His Tyr Lys His Ile Lys Met Ile Asp Lys
3555 3560 3565
cca ctt aga cag aag att gac gtc ctg aag atg ctg gaa gaa gaa
11248Pro Leu Arg Gln Lys Ile Asp Val Leu Lys Met Leu Glu Glu Glu
3570 3575 3580
cgg acg act ccc ttc gag ctg agc cgc gag cct gga tgg agg gta
11293Arg Thr Thr Pro Phe Glu Leu Ser Arg Glu Pro Gly Trp Arg Val
3585 3590 3595
gcg ctg ctg cgt ctg gga gat gac gac cac gtc ctc tcc atc gtc
11338Ala Leu Leu Arg Leu Gly Asp Asp Asp His Val Leu Ser Ile Val
3600 3605 3610
atg cat cac atc atc tcc gac ggt tgg tct gtg gac gtg ctg cgc
11383Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg
3615 3620 3625
cac gag cta ggt cag ttc tac tcg gcc gcg ctc cgg ggg cag gac
11428His Glu Leu Gly Gln Phe Tyr Ser Ala Ala Leu Arg Gly Gln Asp
3630 3635 3640
ccg ttg tcg cag ata agt cct ctg ccg atc cag tat cgt gac ttc
11473Pro Leu Ser Gln Ile Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe
3645 3650 3655
gct ctc tgg cag aga caa gac gag caa gtt gcg gag cat cag cgc
11518Ala Leu Trp Gln Arg Gln Asp Glu Gln Val Ala Glu His Gln Arg
3660 3665 3670
cag ctg gag cat tgg aca gag cag ttg gca gac agt tca ccc gcc
11563Gln Leu Glu His Trp Thr Glu Gln Leu Ala Asp Ser Ser Pro Ala
3675 3680 3685
gag ttg ttg agc gac cac ccg agg cca tcg att ctt tct ggc cag
11608Glu Leu Leu Ser Asp His Pro Arg Pro Ser Ile Leu Ser Gly Gln
3690 3695 3700
gcg ggc gct att ccc gtc aat gtt caa ggc tct ctg tat cag gcg
11653Ala Gly Ala Ile Pro Val Asn Val Gln Gly Ser Leu Tyr Gln Ala
3705 3710 3715
ctt cgg gcg ttc tgc cgc gct cac cag gtc acc tct ttc gta gtc
11698Leu Arg Ala Phe Cys Arg Ala His Gln Val Thr Ser Phe Val Val
3720 3725 3730
ctg ctc acg gcg ttc cgc ata gca cac tat cgt ctg acg ggt gcg
11743Leu Leu Thr Ala Phe Arg Ile Ala His Tyr Arg Leu Thr Gly Ala
3735 3740 3745
gag gac gca acc att gga act ccc att gca aat cgc aac cgg cca
11788Glu Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro
3750 3755 3760
gag ctc gag aac atg atc ggt ttc ttc gtc aat aca caa tgc atg
11833Glu Leu Glu Asn Met Ile Gly Phe Phe Val Asn Thr Gln Cys Met
3765 3770 3775
cgc atc gtc att ggc agt gac gac aca ttt gaa ggg ctg gtg cag
11878Arg Ile Val Ile Gly Ser Asp Asp Thr Phe Glu Gly Leu Val Gln
3780 3785 3790
caa gta cgc tcg ata act gca gct gcc cac gag aac cag gac gtt
11923Gln Val Arg Ser Ile Thr Ala Ala Ala His Glu Asn Gln Asp Val
3795 3800 3805
cca ttc gag cgc atc gtg tca gca ctg ctt ccc ggt tct aga gac
11968Pro Phe Glu Arg Ile Val Ser Ala Leu Leu Pro Gly Ser Arg Asp
3810 3815 3820
aca tca cgc aat cct ctg gtt cag ctc atg ttt gct gtc cac tcg
12013Thr Ser Arg Asn Pro Leu Val Gln Leu Met Phe Ala Val His Ser
3825 3830 3835
caa aga aac ctt ggt cag atc agt cta gaa ggc ctg cag ggt gaa
12058Gln Arg Asn Leu Gly Gln Ile Ser Leu Glu Gly Leu Gln Gly Glu
3840 3845 3850
ttg ctg gga gtg gca gcg act acg aga ttc gat gta gag ttc cat
12103Leu Leu Gly Val Ala Ala Thr Thr Arg Phe Asp Val Glu Phe His
3855 3860 3865
ctc ttc caa gat gac gac aag ctc agc ggc aac gtg ctc ttc gcg
12148Leu Phe Gln Asp Asp Asp Lys Leu Ser Gly Asn Val Leu Phe Ala
3870 3875 3880
acc gag ctc ttc gag cag aag act atg caa ggc atg gtc gac gtg
12193Thr Glu Leu Phe Glu Gln Lys Thr Met Gln Gly Met Val Asp Val
3885 3890 3895
ttc cag gaa gtg ctc agc cgg ggc ctt gag cag ccc cag ata cct
12238Phe Gln Glu Val Leu Ser Arg Gly Leu Glu Gln Pro Gln Ile Pro
3900 3905 3910
ctg gcg acc ctc ccg ctc acg cac gga ctg gag gag ctc agg acc
12283Leu Ala Thr Leu Pro Leu Thr His Gly Leu Glu Glu Leu Arg Thr
3915 3920 3925
atg ggt ctt ctc gac gtg gag aag aca gac tac cct cga gag tcg
12328Met Gly Leu Leu Asp Val Glu Lys Thr Asp Tyr Pro Arg Glu Ser
3930 3935 3940
agc gtg gtg gac gtg ttc cgt gag caa gcg gct gcc tgc tcc gag
12373Ser Val Val Asp Val Phe Arg Glu Gln Ala Ala Ala Cys Ser Glu
3945 3950 3955
gcg att gcg gtc aaa gac tcg tcg gcg cag ctc acc tac tcg gag
12418Ala Ile Ala Val Lys Asp Ser Ser Ala Gln Leu Thr Tyr Ser Glu
3960 3965 3970
ctc gat cga cag tcg gac gag ctt gcc ggc tgg ctg cgc cag caa
12463Leu Asp Arg Gln Ser Asp Glu Leu Ala Gly Trp Leu Arg Gln Gln
3975 3980 3985
cgt ctt cct gcg gag tcg ttg gtt gca gtg ctg gca ccc agg tcg
12508Arg Leu Pro Ala Glu Ser Leu Val Ala Val Leu Ala Pro Arg Ser
3990 3995 4000
tgc cag acc att gtc gcg ttc ctg ggc atc ctc aag gcg aat ctg
12553Cys Gln Thr Ile Val Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu
4005 4010 4015
gca tac ctg ccg cta gac gtc aac gtg ccc gct act cgc ctc gag
12598Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala Thr Arg Leu Glu
4020 4025 4030
tcg ata ctg tct gcc gtc ggc ggc cgg aag ctg gtc ttg ctt gga
12643Ser Ile Leu Ser Ala Val Gly Gly Arg Lys Leu Val Leu Leu Gly
4035 4040 4045
gct gac gtg gcc gac cct ggc ctt cgc ctg gcg gat gtg gag ctc
12688Ala Asp Val Ala Asp Pro Gly Leu Arg Leu Ala Asp Val Glu Leu
4050 4055 4060
gtg cgg atc ggc gac aca ctc ggc cgc tgt gta ccc ggg gcg ccc
12733Val Arg Ile Gly Asp Thr Leu Gly Arg Cys Val Pro Gly Ala Pro
4065 4070 4075
ggc gac aat gag gca cct gtg gtg cag cct tct gcc aca agc ctt
12778Gly Asp Asn Glu Ala Pro Val Val Gln Pro Ser Ala Thr Ser Leu
4080 4085 4090
gcc tac gtc atc ttc act tcc ggc tcg acc ggc aag ccg aag ggt
12823Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly
4095 4100 4105
gtc atg gtc gag cac cgt agt atc gtc cgc ttg atg agg cac agc
12868Val Met Val Glu His Arg Ser Ile Val Arg Leu Met Arg His Ser
4110 4115 4120
aat gtc tcg agt cgc ctt ctg cta cat ccc cgc atg acc cac ctg
12913Asn Val Ser Ser Arg Leu Leu Leu His Pro Arg Met Thr His Leu
4125 4130 4135
tcg aat ctc gcc ttc gat gcg tcg gtg tgg gag att ttc ttg acg
12958Ser Asn Leu Ala Phe Asp Ala Ser Val Trp Glu Ile Phe Leu Thr
4140 4145 4150
ctg ctc aac ggt gga aca ttg att tgt att gac tac ctc tcg tca
13003Leu Leu Asn Gly Gly Thr Leu Ile Cys Ile Asp Tyr Leu Ser Ser
4155 4160 4165
cta gac tgt cgt gct ctt ggg gta agt atc ctg gaa cac cag gtt
13048Leu Asp Cys Arg Ala Leu Gly Val Ser Ile Leu Glu His Gln Val
4170 4175 4180
gac gca tcg gta ctt cct cct gct ttg ctc aaa caa tgc cta gca
13093Asp Ala Ser Val Leu Pro Pro Ala Leu Leu Lys Gln Cys Leu Ala
4185 4190 4195
aat gtc cct gag gca ctt gcg agc ctg caa gtg ctc ttg tcc gct
13138Asn Val Pro Glu Ala Leu Ala Ser Leu Gln Val Leu Leu Ser Ala
4200 4205 4210
gga gat cga ctc gac agt cgt gat gct ata gag agt tgc gca ctc
13183Gly Asp Arg Leu Asp Ser Arg Asp Ala Ile Glu Ser Cys Ala Leu
4215 4220 4225
gtg cgc gga agt gtc tac aat ggg tat ggt ccc acg gag aat ggc
13228Val Arg Gly Ser Val Tyr Asn Gly Tyr Gly Pro Thr Glu Asn Gly
4230 4235 4240
atc cag agc aca atc tat gaa gtc aaa gcg gac gct gag ttt gtc
13273Ile Gln Ser Thr Ile Tyr Glu Val Lys Ala Asp Ala Glu Phe Val
4245 4250 4255
aat ggt gtg cct atc ggc cgc gct gtg agc aac tca ggg gca tat
13318Asn Gly Val Pro Ile Gly Arg Ala Val Ser Asn Ser Gly Ala Tyr
4260 4265 4270
gtc atg gac ccg cag cag caa ctg gtg cct ctc ggg gtg atg ggc
13363Val Met Asp Pro Gln Gln Gln Leu Val Pro Leu Gly Val Met Gly
4275 4280 4285
gag ctc gtc gtc acc ggc gac ggc ctg gcc cgt ggt tac acc gac
13408Glu Leu Val Val Thr Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp
4290 4295 4300
ccg tca ctg gat gcg gac cgc ttt gtg cag gtc tcc gtc aac ggg
13453Pro Ser Leu Asp Ala Asp Arg Phe Val Gln Val Ser Val Asn Gly
4305 4310 4315
cag ctc gtg aga gcg tac cga aca ggc gat cgc gtg cgc tgc agg
13498Gln Leu Val Arg Ala Tyr Arg Thr Gly Asp Arg Val Arg Cys Arg
4320 4325 4330
cct tgc gat ggc cag atc gag ttc ttt gga cgt atg gac cgg caa
13543Pro Cys Asp Gly Gln Ile Glu Phe Phe Gly Arg Met Asp Arg Gln
4335 4340 4345
gtc aag atc cga gga cat cgc atc gag ctc gca gag gta gag cat
13588Val Lys Ile Arg Gly His Arg Ile Glu Leu Ala Glu Val Glu His
4350 4355 4360
gcg gtg ctt ggc ttg gaa gac gtg caa gac gct gcc gtt atc gca
13633Ala Val Leu Gly Leu Glu Asp Val Gln Asp Ala Ala Val Ile Ala
4365 4370 4375
ttt gac aat gtg gac agc gaa gag cca gaa atg gtt ggg ttt gtc
13678Phe Asp Asn Val Asp Ser Glu Glu Pro Glu Met Val Gly Phe Val
4380 4385 4390
act att acc gaa gac aat cct gtc cgt gag gac gaa acc agc ggt
13723Thr Ile Thr Glu Asp Asn Pro Val Arg Glu Asp Glu Thr Ser Gly
4395 4400 4405
caa gta gaa gac tgg gcg aac cac ttc gag ata agt acc tac acc
13768Gln Val Glu Asp Trp Ala Asn His Phe Glu Ile Ser Thr Tyr Thr
4410 4415 4420
gat atc gcg gcg atc gat cag ggt agc att gga agt gac ttt gta
13813Asp Ile Ala Ala Ile Asp Gln Gly Ser Ile Gly Ser Asp Phe Val
4425 4430 4435
ggt tgg act tct atg tac gac gga agc gag atc gac aag gca gag
13858Gly Trp Thr Ser Met Tyr Asp Gly Ser Glu Ile Asp Lys Ala Glu
4440 4445 4450
atg caa gaa tgg ctt gcc gat acc atg gcc tct atg ctc gac ggg
13903Met Gln Glu Trp Leu Ala Asp Thr Met Ala Ser Met Leu Asp Gly
4455 4460 4465
cag gcg ccg ggc aat gtg tta gag ata ggt aca ggc act ggc atg
13948Gln Ala Pro Gly Asn Val Leu Glu Ile Gly Thr Gly Thr Gly Met
4470 4475 4480
gtc ctc ttc aat ctc ggc gac gga ctg cag agc tat gtc ggc ctc
13993Val Leu Phe Asn Leu Gly Asp Gly Leu Gln Ser Tyr Val Gly Leu
4485 4490 4495
gaa cca tca aga tcg gcg gcc gct ttt gtc aac cag acg att aag
14038Glu Pro Ser Arg Ser Ala Ala Ala Phe Val Asn Gln Thr Ile Lys
4500 4505 4510
tcg ctc ccc acc ctt gct ggc aac gct gaa gta cac att ggc act
14083Ser Leu Pro Thr Leu Ala Gly Asn Ala Glu Val His Ile Gly Thr
4515 4520 4525
gcg acc gac gtg gcc cgt cta gat ggc ctc cgc ccc gac tta gtg
14128Ala Thr Asp Val Ala Arg Leu Asp Gly Leu Arg Pro Asp Leu Val
4530 4535 4540
gta gtc aat tcg gta gtc cag tac ttc cca tca cca gag tac cta
14173Val Val Asn Ser Val Val Gln Tyr Phe Pro Ser Pro Glu Tyr Leu
4545 4550 4555
atg gaa gtc gtg gag gct ctt gca cgt ctg ccg ggc gtc gag cga
14218Met Glu Val Val Glu Ala Leu Ala Arg Leu Pro Gly Val Glu Arg
4560 4565 4570
att ttc ttc gga gac gta cgt tcg tac gcc atc aac aga gat ttc
14263Ile Phe Phe Gly Asp Val Arg Ser Tyr Ala Ile Asn Arg Asp Phe
4575 4580 4585
ctg gct gcc aga gct cta cac gaa ctt ggc gac aga gcg act aag
14308Leu Ala Ala Arg Ala Leu His Glu Leu Gly Asp Arg Ala Thr Lys
4590 4595 4600
cac gag att cgg cga aag atg cta gag atg gaa gaa cgc gaa gag
14353His Glu Ile Arg Arg Lys Met Leu Glu Met Glu Glu Arg Glu Glu
4605 4610 4615
gag ctg ctc gtc gac cca gct ttc ttc acc atg ttg acc agc agt
14398Glu Leu Leu Val Asp Pro Ala Phe Phe Thr Met Leu Thr Ser Ser
4620 4625 4630
ctc cct ggc ctg att cag cat gtc gag atc ttg ccg aag ctg atg
14443Leu Pro Gly Leu Ile Gln His Val Glu Ile Leu Pro Lys Leu Met
4635 4640 4645
aga gcc act aat gag ctc agc gcg tat cga tac act gct gta gta
14488Arg Ala Thr Asn Glu Leu Ser Ala Tyr Arg Tyr Thr Ala Val Val
4650 4655 4660
cac gtg tgc cgt gcc ggt caa gag cct cgt tcc gtg cat acg atc
14533His Val Cys Arg Ala Gly Gln Glu Pro Arg Ser Val His Thr Ile
4665 4670 4675
gac gac gat gcc tgg gtg aat ctt gga gct tct cgg ttg agt cgc
14578Asp Asp Asp Ala Trp Val Asn Leu Gly Ala Ser Arg Leu Ser Arg
4680 4685 4690
cct acc ctt tca agc ctt ttg caa act tcc gag ggc gca tcg gcc
14623Pro Thr Leu Ser Ser Leu Leu Gln Thr Ser Glu Gly Ala Ser Ala
4695 4700 4705
gtc gca gta agc aat att cct tac agc aag acc atc aca gag cga
14668Val Ala Val Ser Asn Ile Pro Tyr Ser Lys Thr Ile Thr Glu Arg
4710 4715 4720
gcg ctc gtt agt gcg ctc gat gag gat gat atg caa gac tca tcg
14713Ala Leu Val Ser Ala Leu Asp Glu Asp Asp Met Gln Asp Ser Ser
4725 4730 4735
gac tgg ctg ctg gcc gtg cgc gag aca ggc aga tct tgt tcc tcc
14758Asp Trp Leu Leu Ala Val Arg Glu Thr Gly Arg Ser Cys Ser Ser
4740 4745 4750
ttc tcc gca aca gac ctt gtc gag ctt gct cga gag acg ggc tgg
14803Phe Ser Ala Thr Asp Leu Val Glu Leu Ala Arg Glu Thr Gly Trp
4755 4760 4765
cgt gtg gag ctc agc tgg gca cga cag tac tca cag aaa ggc gca
14848Arg Val Glu Leu Ser Trp Ala Arg Gln Tyr Ser Gln Lys Gly Ala
4770 4775 4780
ctc gat gct gtc ttc cac aga cac cct gtt tcc gct ggg agc ggg
14893Leu Asp Ala Val Phe His Arg His Pro Val Ser Ala Gly Ser Gly
4785 4790 4795
cgt gtc atg ttc cag ttt cca gtt gag acc gaa gat cga ccg cac
14938Arg Val Met Phe Gln Phe Pro Val Glu Thr Glu Asp Arg Pro His
4800 4805 4810
atc tca cgc acg aac cga cct tta cag cga ttg cag aag aag cga
14983Ile Ser Arg Thr Asn Arg Pro Leu Gln Arg Leu Gln Lys Lys Arg
4815 4820 4825
acc gag aca cat gtt cat gag cag ttg cgg gct ttg ctt cca cga
15028Thr Glu Thr His Val His Glu Gln Leu Arg Ala Leu Leu Pro Arg
4830 4835 4840
tac atg gtt cct acg cgg att gtg gcg ctt gat aag ctg ccc gtc
15073Tyr Met Val Pro Thr Arg Ile Val Ala Leu Asp Lys Leu Pro Val
4845 4850 4855
aat gca aac ggc aag gtt gat cgt caa cag ctc gct agg aca gcc
15118Asn Ala Asn Gly Lys Val Asp Arg Gln Gln Leu Ala Arg Thr Ala
4860 4865 4870
cag gtt ctc cca gcg agc aag gcg ccg tct gca tgc gtg gcc cca
15163Gln Val Leu Pro Ala Ser Lys Ala Pro Ser Ala Cys Val Ala Pro
4875 4880 4885
cgc aac gaa ttg gaa atg aca ctg tgt gaa gag ttc tcg cag gtt
15208Arg Asn Glu Leu Glu Met Thr Leu Cys Glu Glu Phe Ser Gln Val
4890 4895 4900
ctt ggc gtc gag gtc ggc att act gac aat ttc ttc cac ctg ggt
15253Leu Gly Val Glu Val Gly Ile Thr Asp Asn Phe Phe His Leu Gly
4905 4910 4915
ggc cac tct ctc atg gca aca aag ctt gcc gct cgt atc agc cac
15298Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala Arg Ile Ser His
4920 4925 4930
cgc ctt cat aca cgc ata tcc gtc aaa cac atc ttc gat cac cct
15343Arg Leu His Thr Arg Ile Ser Val Lys His Ile Phe Asp His Pro
4935 4940 4945
ttg ata ggc gat ttg tct gtc cac ata gct gac tct ccg gtg cct
15388Leu Ile Gly Asp Leu Ser Val His Ile Ala Asp Ser Pro Val Pro
4950 4955 4960
ctt ttg aca atc aca cgt gcc cag cac gct gga gca gtg gag cag
15433Leu Leu Thr Ile Thr Arg Ala Gln His Ala Gly Ala Val Glu Gln
4965 4970 4975
tca ttc gca caa gct aga ttg tgg ttc ctt gtc cag cta gga ctt
15478Ser Phe Ala Gln Ala Arg Leu Trp Phe Leu Val Gln Leu Gly Leu
4980 4985 4990
gaa tct cct tcg tac atc ata cca att gta ttg cgt tta cac ggt
15523Glu Ser Pro Ser Tyr Ile Ile Pro Ile Val Leu Arg Leu His Gly
4995 5000 5005
tca ctc tca aag act gcc att gaa gga gct cta tca gcc ctg atg
15568Ser Leu Ser Lys Thr Ala Ile Glu Gly Ala Leu Ser Ala Leu Met
5010 5015 5020
gaa cgt cat gag gtc ctt cgt acg acg ttc gag gac cat aag ggt
15613Glu Arg His Glu Val Leu Arg Thr Thr Phe Glu Asp His Lys Gly
5025 5030 5035
atc ggc atg caa gtg gta caa gac cat cgt cac caa gac ttg gtt
15658Ile Gly Met Gln Val Val Gln Asp His Arg His Gln Asp Leu Val
5040 5045 5050
gta att gac gtt gca ggt cag ggg tca ctc gac tac aag cag cac
15703Val Ile Asp Val Ala Gly Gln Gly Ser Leu Asp Tyr Lys Gln His
5055 5060 5065
tta tac atg gag cac gtg aaa cct ttc gat ctg acc cgg gat cct
15748Leu Tyr Met Glu His Val Lys Pro Phe Asp Leu Thr Arg Asp Pro
5070 5075 5080
ggg tgg agg gta gcg ctg ctg cgt ctg gga gat gac gac cac gtc
15793Gly Trp Arg Val Ala Leu Leu Arg Leu Gly Asp Asp Asp His Val
5085 5090 5095
ctc tcc atc gta atg cat cac atc atc tcc gat ggc tgg tcg att
15838Leu Ser Ile Val Met His His Ile Ile Ser Asp Gly Trp Ser Ile
5100 5105 5110
gat atc ctg ctg cgt gag ttg ggt cag ttc tac tcg gcc gcg ctc
15883Asp Ile Leu Leu Arg Glu Leu Gly Gln Phe Tyr Ser Ala Ala Leu
5115 5120 5125
cgg ggg cag gac ccg ttg tca cag aca agt cct ctg ccg atc cag
15928Arg Gly Gln Asp Pro Leu Ser Gln Thr Ser Pro Leu Pro Ile Gln
5130 5135 5140
tat cgt gac ttc gct ctc tgg caa aag cag gat cat caa tta gcc
15973Tyr Arg Asp Phe Ala Leu Trp Gln Lys Gln Asp His Gln Leu Ala
5145 5150 5155
gat cac gag aag cag ctg cgg tat tgg gaa gag caa ctg gcg gag
16018Asp His Glu Lys Gln Leu Arg Tyr Trp Glu Glu Gln Leu Ala Glu
5160 5165 5170
agc tct cca gct gag ctg cta tgt gat cat gca cgt ccg acg acg
16063Ser Ser Pro Ala Glu Leu Leu Cys Asp His Ala Arg Pro Thr Thr
5175 5180 5185
ccc tca ggt cag gca ggc tcg att ccc gtc aat gtt caa ggc tct
16108Pro Ser Gly Gln Ala Gly Ser Ile Pro Val Asn Val Gln Gly Ser
5190 5195 5200
ctg tat cag gcg ctt cgg gcg ttc tgc cgc gct cac cag gtc acc
16153Leu Tyr Gln Ala Leu Arg Ala Phe Cys Arg Ala His Gln Val Thr
5205 5210 5215
tct ttc gta gtc ctg ctc acg gcg ttc cgc ata gca cac tat cgt
16198Ser Phe Val Val Leu Leu Thr Ala Phe Arg Ile Ala His Tyr Arg
5220 5225 5230
ctg acg ggt gcg gag gac gca acc att gga act ccc att gca aat
16243Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn
5235 5240 5245
cgc aac cgg cca gag ctc gag aac atg atc ggt ttc ttc gtc aat
16288Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Phe Phe Val Asn
5250 5255 5260
aca caa tgc atg cgc atc gtc att ggc agt gac gac aca ttt gaa
16333Thr Gln Cys Met Arg Ile Val Ile Gly Ser Asp Asp Thr Phe Glu
5265 5270 5275
ggg ctg gtg cag caa gta cgc tcg ata act gca gct gcc cac gag
16378Gly Leu Val Gln Gln Val Arg Ser Ile Thr Ala Ala Ala His Glu
5280 5285 5290
aac cag gac gtt cca ttc gag cgc atc gtg tca gca ctg ctt ccc
16423Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ala Leu Leu Pro
5295 5300 5305
ggt tct aga gac aca tca cgc aat cct ctg gtg cag ttg ttg ttc
16468Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Leu Phe
5310 5315 5320
gct gtt cat gcc tat caa gag gtc gaa aat ttc gcc atc ccc ggt
16513Ala Val His Ala Tyr Gln Glu Val Glu Asn Phe Ala Ile Pro Gly
5325 5330 5335
gtg cac tcc gag ttg gtg caa gga acg acc ttt aca aga ttt gat
16558Val His Ser Glu Leu Val Gln Gly Thr Thr Phe Thr Arg Phe Asp
5340 5345 5350
gtc gag ttc cac ctg ctt gaa gac cct gac aag ctc agc ggc aac
16603Val Glu Phe His Leu Leu Glu Asp Pro Asp Lys Leu Ser Gly Asn
5355 5360 5365
gtg ctc ttc gcg acc gag ctc ttc gag cag aag act atg caa ggc
16648Val Leu Phe Ala Thr Glu Leu Phe Glu Gln Lys Thr Met Gln Gly
5370 5375 5380
atg gtc gac gtg ttc cag gaa gtg ctc agc cgg ggc ctt gag cag
16693Met Val Asp Val Phe Gln Glu Val Leu Ser Arg Gly Leu Glu Gln
5385 5390 5395
ccc cag ata cct ctg gcg acc ctc ccg ctc acg cac gga ctg gag
16738Pro Gln Ile Pro Leu Ala Thr Leu Pro Leu Thr His Gly Leu Glu
5400 5405 5410
gag ctc agg acc atg ggt ctt ctc gac gtg gag aag aca gac tac
16783Glu Leu Arg Thr Met Gly Leu Leu Asp Val Glu Lys Thr Asp Tyr
5415 5420 5425
cct cga gag tcg agc gtg gtg gac gtg ttc cgt gag caa gcg gct
16828Pro Arg Glu Ser Ser Val Val Asp Val Phe Arg Glu Gln Ala Ala
5430 5435 5440
gcc tgc tcc gag gcg att gcg gtc aaa gac tcg tcg gcg cag ctc
16873Ala Cys Ser Glu Ala Ile Ala Val Lys Asp Ser Ser Ala Gln Leu
5445 5450 5455
acc tac tcg gag ctc gat cga cag tcg gac gag ctt gcc ggc tgg
16918Thr Tyr Ser Glu Leu Asp Arg Gln Ser Asp Glu Leu Ala Gly Trp
5460 5465 5470
ctg cgc cag caa cgt ctt cct gcg gag tcg ttg gtt gca gtg ctg
16963Leu Arg Gln Gln Arg Leu Pro Ala Glu Ser Leu Val Ala Val Leu
5475 5480 5485
gca ccc agg tcg tgc cag acc att gtc gcg ttc ctg ggc atc ctc
17008Ala Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Ile Leu
5490 5495 5500
aag gcg aat ctg gca tac ctg ccg cta gac gtc aac gtg ccc gct
17053Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala
5505 5510 5515
act cgc ctc gag tcg ata ctg tct gcc gtc ggc ggc cgg aag ctg
17098Thr Arg Leu Glu Ser Ile Leu Ser Ala Val Gly Gly Arg Lys Leu
5520 5525 5530
gtc ttg ctt gga gct gac gtg gcc gac cct ggc ctt cgc ctg gcg
17143Val Leu Leu Gly Ala Asp Val Ala Asp Pro Gly Leu Arg Leu Ala
5535 5540 5545
gat gtg gag ctc gtg cgg atc ggc gac aca ctc ggc cgc tgt gta
17188Asp Val Glu Leu Val Arg Ile Gly Asp Thr Leu Gly Arg Cys Val
5550 5555 5560
ccc ggg gcg ccc ggc gac aat gag gca cct gtg gtg cag cct tct
17233Pro Gly Ala Pro Gly Asp Asn Glu Ala Pro Val Val Gln Pro Ser
5565 5570 5575
gcc aca agc ctt gcc tac gtc atc ttc act tcc ggc tcg acc ggc
17278Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly
5580 5585 5590
aag ccg aag ggt gtc atg gtc gag cac cgc agt ata ctc agg gtt
17323Lys Pro Lys Gly Val Met Val Glu His Arg Ser Ile Leu Arg Val
5595 5600 5605
gtc acg tct ccc ccg gcc cgt gct ctg cta ccg tcc aca atc atc
17368Val Thr Ser Pro Pro Ala Arg Ala Leu Leu Pro Ser Thr Ile Ile
5610 5615 5620
atg gcc cac ctg aca aac att gca ttc gat gta tcg cta tgg gag
17413Met Ala His Leu Thr Asn Ile Ala Phe Asp Val Ser Leu Trp Glu
5625 5630 5635
ata tgt aca gct ctt ctt cac ggt ggt acc ctg atc tgt att cag
17458Ile Cys Thr Ala Leu Leu His Gly Gly Thr Leu Ile Cys Ile Gln
5640 5645 5650
tat ctt gcc tcg ctc gat gtc agg ggg ctt cag act aca ttc tct
17503Tyr Leu Ala Ser Leu Asp Val Arg Gly Leu Gln Thr Thr Phe Ser
5655 5660 5665
cgc gaa gct atc aac gta gct gtg ttt cct cct gcc ttg cta aag
17548Arg Glu Ala Ile Asn Val Ala Val Phe Pro Pro Ala Leu Leu Lys
5670 5675 5680
acc tgt ctt gcc aag att cca tct gct cta gca tcg ctg agt gcc
17593Thr Cys Leu Ala Lys Ile Pro Ser Ala Leu Ala Ser Leu Ser Ala
5685 5690 5695
atg ttc tcg tcc gga gat cgt ctc gac tca cgc gat gct agc gag
17638Met Phe Ser Ser Gly Asp Arg Leu Asp Ser Arg Asp Ala Ser Glu
5700 5705 5710
ggg gcc aca ctt gtg cgg caa ggg ata cac aac gcg tat ggt ccc
17683Gly Ala Thr Leu Val Arg Gln Gly Ile His Asn Ala Tyr Gly Pro
5715 5720 5725
acg gag aat ggc atc cag agc aca atc tat gaa gtc aaa gcg gac
17728Thr Glu Asn Gly Ile Gln Ser Thr Ile Tyr Glu Val Lys Ala Asp
5730 5735 5740
gct gag ttt gtc aat ggt gtg cct atc ggc cgc gct gtg agc aac
17773Ala Glu Phe Val Asn Gly Val Pro Ile Gly Arg Ala Val Ser Asn
5745 5750 5755
tca ggg gca tat gtc atg gac ccg cag cag caa ctg gtg cct ctc
17818Ser Gly Ala Tyr Val Met Asp Pro Gln Gln Gln Leu Val Pro Leu
5760 5765 5770
ggg gtg atg ggc gag ctc gtc gtc acc ggc gac ggc ctg gcc cgt
17863Gly Val Met Gly Glu Leu Val Val Thr Gly Asp Gly Leu Ala Arg
5775 5780 5785
ggt tac acc gac ccg tca ctg gat gcg gac cgc ttt gtg cag gtc
17908Gly Tyr Thr Asp Pro Ser Leu Asp Ala Asp Arg Phe Val Gln Val
5790 5795 5800
tcc gtc aac ggg cag ctc gtg aga gcg tac cga aca ggc gat cgc
17953Ser Val Asn Gly Gln Leu Val Arg Ala Tyr Arg Thr Gly Asp Arg
5805 5810 5815
gtg cgc tgc agg cct tgc gat ggc cag atc gag ttc ttt gga cgt
17998Val Arg Cys Arg Pro Cys Asp Gly Gln Ile Glu Phe Phe Gly Arg
5820 5825 5830
atg gac cgg caa gtc aag atc cga gga cat cgc atc gag ctc gca
18043Met Asp Arg Gln Val Lys Ile Arg Gly His Arg Ile Glu Leu Ala
5835 5840 5845
gag gta gag cat gcg ata ttg tcc ctt gat tat gtg atc gat gca
18088Glu Val Glu His Ala Ile Leu Ser Leu Asp Tyr Val Ile Asp Ala
5850 5855 5860
gcc gtc ctt ctg aga cag ctg att gat caa gag cca caa gtg gta
18133Ala Val Leu Leu Arg Gln Leu Ile Asp Gln Glu Pro Gln Val Val
5865 5870 5875
gga ttc gtc att gta tcc acc aaa cgg gct tat tcc cga cac aac
18178Gly Phe Val Ile Val Ser Thr Lys Arg Ala Tyr Ser Arg His Asn
5880 5885 5890
agc ggc tac gcg tct gaa gtt tcg gca ttc tgc atc aaa gat cag
18223Ser Gly Tyr Ala Ser Glu Val Ser Ala Phe Cys Ile Lys Asp Gln
5895 5900 5905
atc gca tgg cgc att cga caa cat ctc tgc agg atg ctg cct tcc
18268Ile Ala Trp Arg Ile Arg Gln His Leu Cys Arg Met Leu Pro Ser
5910 5915 5920
tat atg gtt ccc tat caa att gca att ctt gat gaa atg cct atc
18313Tyr Met Val Pro Tyr Gln Ile Ala Ile Leu Asp Glu Met Pro Ile
5925 5930 5935
aat gct aac ggc aag gtg gat aga cag aat ctt gca agc aga act
18358Asn Ala Asn Gly Lys Val Asp Arg Gln Asn Leu Ala Ser Arg Thr
5940 5945 5950
gtc aac gtc caa aga atc ctc gcc gct cca tac atg gcc ccg cgc
18403Val Asn Val Gln Arg Ile Leu Ala Ala Pro Tyr Met Ala Pro Arg
5955 5960 5965
aat gaa gtc gag att tcg ctt tgc gaa cag tat gct gcc ctg ctt
18448Asn Glu Val Glu Ile Ser Leu Cys Glu Gln Tyr Ala Ala Leu Leu
5970 5975 5980
gaa cac gac gtt ggc att ctt gac gac ttc ttc gaa ctt ggt ggt
18493Glu His Asp Val Gly Ile Leu Asp Asp Phe Phe Glu Leu Gly Gly
5985 5990 5995
cac tct ctc atg gct act aga ctg gcc tcg cgt atc agc tcc cga
18538His Ser Leu Met Ala Thr Arg Leu Ala Ser Arg Ile Ser Ser Arg
6000 6005 6010
ttc agc gct ccg gtg tct gtt cgt gat att ttc gac cat cca aga
18583Phe Ser Ala Pro Val Ser Val Arg Asp Ile Phe Asp His Pro Arg
6015 6020 6025
atc atg gac ctt gct agc atc att cgt gct gga gac att caa tgg
18628Ile Met Asp Leu Ala Ser Ile Ile Arg Ala Gly Asp Ile Gln Trp
6030 6035 6040
tcc cgg ata ctg cct tct gct tat gaa cgt cca gtc gag caa tct
18673Ser Arg Ile Leu Pro Ser Ala Tyr Glu Arg Pro Val Glu Gln Ser
6045 6050 6055
ttc gca cag aat cgc ctg tgg ttc ctg tac aag ctt gac ata ggt
18718Phe Ala Gln Asn Arg Leu Trp Phe Leu Tyr Lys Leu Asp Ile Gly
6060 6065 6070
acg aca cag tat aat tta ccg ctg gcg ata cac ctt cga gga cca
18763Thr Thr Gln Tyr Asn Leu Pro Leu Ala Ile His Leu Arg Gly Pro
6075 6080 6085
cta gat ata tca gcg ctg ttt atc gca ttc aag gca ttg act gaa
18808Leu Asp Ile Ser Ala Leu Phe Ile Ala Phe Lys Ala Leu Thr Glu
6090 6095 6100
aga cat gaa ctt ttg cgc aca act ttt gat gag gat gac gga aca
18853Arg His Glu Leu Leu Arg Thr Thr Phe Asp Glu Asp Asp Gly Thr
6105 6110 6115
tgc ctg cag atg tta ttg cct gaa tat cag cat gaa gta agg atc
18898Cys Leu Gln Met Leu Leu Pro Glu Tyr Gln His Glu Val Arg Ile
6120 6125 6130
acc gac ttg cag gga tca cac aaa ggt agc ctc ctg gat att ctc
18943Thr Asp Leu Gln Gly Ser His Lys Gly Ser Leu Leu Asp Ile Leu
6135 6140 6145
aac aac aat cag aag act ccc ttc gag ctg agc cgc gag cct gga
18988Asn Asn Asn Gln Lys Thr Pro Phe Glu Leu Ser Arg Glu Pro Gly
6150 6155 6160
tgg agg gta gcg ctg ctg cgt ctg gga gat gac gac cac gtc ctc
19033Trp Arg Val Ala Leu Leu Arg Leu Gly Asp Asp Asp His Val Leu
6165 6170 6175
tcc atc gtc atg cat cac atc atc tcc gac ggt tgg tct gtg gac
19078Ser Ile Val Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp
6180 6185 6190
gtg ctg cgc cac gag cta ggt cag ttc tac tcg gcc gcg ctc cgg
19123Val Leu Arg His Glu Leu Gly Gln Phe Tyr Ser Ala Ala Leu Arg
6195 6200 6205
ggg cag gac ccg ttg tcg cag ata agt cct ctg ccg atc cag tat
19168Gly Gln Asp Pro Leu Ser Gln Ile Ser Pro Leu Pro Ile Gln Tyr
6210 6215 6220
cgt gac ttc gct ctc tgg cag aga caa gac gag caa gtt gcg gag
19213Arg Asp Phe Ala Leu Trp Gln Arg Gln Asp Glu Gln Val Ala Glu
6225 6230 6235
cat cag cgc cag ctg gag cat tgg aca gag cag ttg gca gac agt
19258His Gln Arg Gln Leu Glu His Trp Thr Glu Gln Leu Ala Asp Ser
6240 6245 6250
tca ccc gcc gag ttg ttg agc gac cac ccg agg cca tcg att ctt
19303Ser Pro Ala Glu Leu Leu Ser Asp His Pro Arg Pro Ser Ile Leu
6255 6260 6265
tct ggc cag gcg ggc gct att ccc gtc aat gtt caa ggc tct ctg
19348Ser Gly Gln Ala Gly Ala Ile Pro Val Asn Val Gln Gly Ser Leu
6270 6275 6280
tat cag gcg ctt cgg gcg ttc tgc cgc gct cac cag gtc acc tct
19393Tyr Gln Ala Leu Arg Ala Phe Cys Arg Ala His Gln Val Thr Ser
6285 6290 6295
ttc gta gtc ctg ctc acg gcg ttc cgc ata gca cac tat cgt ctg
19438Phe Val Val Leu Leu Thr Ala Phe Arg Ile Ala His Tyr Arg Leu
6300 6305 6310
acg ggt gcg gag gac gca acc att gga act ccc att gca aat cgc
19483Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn Arg
6315 6320 6325
aac cgg cca gag ctc gag aac atg atc ggt ttc ttc gtc aat aca
19528Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Phe Phe Val Asn Thr
6330 6335 6340
caa tgc atg cgc atc gtc att ggc agt gac gac aca ttt gaa ggg
19573Gln Cys Met Arg Ile Val Ile Gly Ser Asp Asp Thr Phe Glu Gly
6345 6350 6355
ctg gtg cag caa gta cgc tcg ata act gca gct gcc cac gag aac
19618Leu Val Gln Gln Val Arg Ser Ile Thr Ala Ala Ala His Glu Asn
6360 6365 6370
cag gac gtt cca ttc gag cgc atc gtg tca gca ctg ctt ccc ggt
19663Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ala Leu Leu Pro Gly
6375 6380 6385
tct aga gac aca tca cgc aat cct ctg gtt cag ctc atg ttt gct
19708Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Met Phe Ala
6390 6395 6400
gtc cac tcg caa aga aac ctt ggt cag atc agt cta gaa ggc ctg
19753Val His Ser Gln Arg Asn Leu Gly Gln Ile Ser Leu Glu Gly Leu
6405 6410 6415
cag ggt gaa ttg ctg gga gtg gca gcg act acg aga ttc gat gta
19798Gln Gly Glu Leu Leu Gly Val Ala Ala Thr Thr Arg Phe Asp Val
6420 6425 6430
gag ttc cat ctc ttc caa gat gac gac aag ctc agc ggc aac gtg
19843Glu Phe His Leu Phe Gln Asp Asp Asp Lys Leu Ser Gly Asn Val
6435 6440 6445
ctc ttc gcg acc gag ctc ttc gag cag aag act atg caa ggc atg
19888Leu Phe Ala Thr Glu Leu Phe Glu Gln Lys Thr Met Gln Gly Met
6450 6455 6460
gtc gac gtg ttc cag gaa gtg ctc agc cgg ggc ctt gag cag ccc
19933Val Asp Val Phe Gln Glu Val Leu Ser Arg Gly Leu Glu Gln Pro
6465 6470 6475
cag ata cct ctg gcg acc ctc ccg ctc acg cac gga ctg gag gag
19978Gln Ile Pro Leu Ala Thr Leu Pro Leu Thr His Gly Leu Glu Glu
6480 6485 6490
ctc agg acc atg ggt ctt ctc gac gtg gag aag aca gac tac cct
20023Leu Arg Thr Met Gly Leu Leu Asp Val Glu Lys Thr Asp Tyr Pro
6495 6500 6505
cga gag tcg agc gtg gtg gac gtg ttc cgt gag caa gcg gct gcc
20068Arg Glu Ser Ser Val Val Asp Val Phe Arg Glu Gln Ala Ala Ala
6510 6515 6520
tgc tcc gag gcg att gcg gtc aaa gac tcg tcg gcg cag ctc acc
20113Cys Ser Glu Ala Ile Ala Val Lys Asp Ser Ser Ala Gln Leu Thr
6525 6530 6535
tac tcg gag ctc gat cga cag tcg gac gag ctt gcc ggc tgg ctg
20158Tyr Ser Glu Leu Asp Arg Gln Ser Asp Glu Leu Ala Gly Trp Leu
6540 6545 6550
cgc cag caa cgt ctt cct gcg gag tcg ttg gtt gca gtg ctg gca
20203Arg Gln Gln Arg Leu Pro Ala Glu Ser Leu Val Ala Val Leu Ala
6555 6560 6565
ccc agg tcg tgc cag acc att gtc gcg ttc ctg ggc atc ctc aag
20248Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Ile Leu Lys
6570 6575 6580
gcg aat ctg gca tac ctg ccg cta gac gtc aac gtg ccc gct act
20293Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala Thr
6585 6590 6595
cgc ctc gag tcg ata ctg tct gcc gtc ggc ggc cgg aag ctg gtc
20338Arg Leu Glu Ser Ile Leu Ser Ala Val Gly Gly Arg Lys Leu Val
6600 6605 6610
ttg ctt gga gct gac gtg gcc gac cct ggc ctt cgc ctg gcg gat
20383Leu Leu Gly Ala Asp Val Ala Asp Pro Gly Leu Arg Leu Ala Asp
6615 6620 6625
gtg gag ctc gtg cgg atc ggc gac aca ctc ggc cgc tgt gta ccc
20428Val Glu Leu Val Arg Ile Gly Asp Thr Leu Gly Arg Cys Val Pro
6630 6635 6640
ggg gcg ccc ggc gac aac gag gca cct gtg gtg cag cct tct gcc
20473Gly Ala Pro Gly Asp Asn Glu Ala Pro Val Val Gln Pro Ser Ala
6645 6650 6655
aca agc ctt gcc tac gtc atc ttc act tcc ggc tcg acc ggc aag
20518Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys
6660 6665 6670
ccg aag ggt gtc atg gtc gag cac cgg ggt gta gtg cga ctt gtc
20563Pro Lys Gly Val Met Val Glu His Arg Gly Val Val Arg Leu Val
6675 6680 6685
aag cag agc aat gtt gtc tac cat ctc ccg tcc aca tct cgc gtg
20608Lys Gln Ser Asn Val Val Tyr His Leu Pro Ser Thr Ser Arg Val
6690 6695 6700
gcc cac ctg tcg aat ctc gcc ttt gat gcc tcg gtc ctc gag atc
20653Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ser Val Leu Glu Ile
6705 6710 6715
tat gcg gcc ctt ctg aac ggt ggt act gtt tac tgc att gac tat
20698Tyr Ala Ala Leu Leu Asn Gly Gly Thr Val Tyr Cys Ile Asp Tyr
6720 6725 6730
ctc act acc ctt gac cct cac gcg ctt gag tct gtt ttc atc gat
20743Leu Thr Thr Leu Asp Pro His Ala Leu Glu Ser Val Phe Ile Asp
6735 6740 6745
gct gat ctc aac acg gca gtc ctt cct ccc gct cta ctt aaa cag
20788Ala Asp Leu Asn Thr Ala Val Leu Pro Pro Ala Leu Leu Lys Gln
6750 6755 6760
gtc ctt gct tcg agc cct tct acc ctc cat gcc ctt gat tta ctc
20833Val Leu Ala Ser Ser Pro Ser Thr Leu His Ala Leu Asp Leu Leu
6765 6770 6775
ttc ata gga gga gat cga ttg gat gct cgt gac gcc ctg tac gct
20878Phe Ile Gly Gly Asp Arg Leu Asp Ala Arg Asp Ala Leu Tyr Ala
6780 6785 6790
aat cgt ctg gtt cga ggg tca tta tac aat gtc tat ggc ccg aca
20923Asn Arg Leu Val Arg Gly Ser Leu Tyr Asn Val Tyr Gly Pro Thr
6795 6800 6805
gag aac acc gtt ctg agc gtc gtt tac ctc ttt aat gat gac gat
20968Glu Asn Thr Val Leu Ser Val Val Tyr Leu Phe Asn Asp Asp Asp
6810 6815 6820
gca tgc att aat ggc gtc cct atc ggc caa gtc gtc agt aat tcc
21013Ala Cys Ile Asn Gly Val Pro Ile Gly Gln Val Val Ser Asn Ser
6825 6830 6835
ggg gta tac gtc atg gac tca gaa cag aaa tta gta cct cct ggg
21058Gly Val Tyr Val Met Asp Ser Glu Gln Lys Leu Val Pro Pro Gly
6840 6845 6850
gtc atg gga gaa atc gtc gtg aca gga gac ggt ctc gca aga ggg
21103Val Met Gly Glu Ile Val Val Thr Gly Asp Gly Leu Ala Arg Gly
6855 6860 6865
tat act gac tca acc tta aat act gat cgt ttc gtt caa atc agt
21148Tyr Thr Asp Ser Thr Leu Asn Thr Asp Arg Phe Val Gln Ile Ser
6870 6875 6880
gtc aac gga cgt gta ctg caa gca tac cgt aca ggc gat cgt ggt
21193Val Asn Gly Arg Val Leu Gln Ala Tyr Arg Thr Gly Asp Arg Gly
6885 6890 6895
cgg tac cgc ccg aca gac gct cgt ctt gag ttc ttt ggc cgt cta
21238Arg Tyr Arg Pro Thr Asp Ala Arg Leu Glu Phe Phe Gly Arg Leu
6900 6905 6910
gat caa caa atc aag ctt cgc ggg cat cgt gta gag ctc aaa gaa
21283Asp Gln Gln Ile Lys Leu Arg Gly His Arg Val Glu Leu Lys Glu
6915 6920 6925
atc gag caa gcg atg ctt ggc cac aat gct gtt gat gat gca gga
21328Ile Glu Gln Ala Met Leu Gly His Asn Ala Val Asp Asp Ala Gly
6930 6935 6940
gtt gtc gct ctg gag ata tct gag tgc caa gag cta gag atg gtt
21373Val Val Ala Leu Glu Ile Ser Glu Cys Gln Glu Leu Glu Met Val
6945 6950 6955
ggc ttt gtg act cta cgc aat ctt gga acc atg gaa gca act aac
21418Gly Phe Val Thr Leu Arg Asn Leu Gly Thr Met Glu Ala Thr Asn
6960 6965 6970
aat ctc gca cac aca agc tgg aac cca gtg act ctc aaa acc cct
21463Asn Leu Ala His Thr Ser Trp Asn Pro Val Thr Leu Lys Thr Pro
6975 6980 6985
tta gca tca caa ata gtg gct gag gtt cgg ggt aga ctc cag cga
21508Leu Ala Ser Gln Ile Val Ala Glu Val Arg Gly Arg Leu Gln Arg
6990 6995 7000
aat ctg cca ctc tat atg gta ccc gct acg att gtg gta tta cat
21553Asn Leu Pro Leu Tyr Met Val Pro Ala Thr Ile Val Val Leu His
7005 7010 7015
act atg cca gtc aat gcc aac ggg aag ctc gac cga caa gca ctt
21598Thr Met Pro Val Asn Ala Asn Gly Lys Leu Asp Arg Gln Ala Leu
7020 7025 7030
gtg aaa gct gca atg acg ctt cca aaa act gct cca ctg gta tgg
21643Val Lys Ala Ala Met Thr Leu Pro Lys Thr Ala Pro Leu Val Trp
7035 7040 7045
atg gct ccg cgc aat gaa gga gag aca tcg cta tgt gag gag cta
21688Met Ala Pro Arg Asn Glu Gly Glu Thr Ser Leu Cys Glu Glu Leu
7050 7055 7060
aca gat atc ttg ggg gtg aac gtc ggg atc acc gat aac ttt ttt
21733Thr Asp Ile Leu Gly Val Asn Val Gly Ile Thr Asp Asn Phe Phe
7065 7070 7075
gac ctt ggg ggg cat tcc ctc ctg gca acc aga gta gcc gcg cga
21778Asp Leu Gly Gly His Ser Leu Leu Ala Thr Arg Val Ala Ala Arg
7080 7085 7090
atc agc cga cgt ctt gat gcc ctg gtg acc gtc aaa caa ata ttc
21823Ile Ser Arg Arg Leu Asp Ala Leu Val Thr Val Lys Gln Ile Phe
7095 7100 7105
gac cat cca gtc att gga gat ctc gca gct gca att caa ggg ggt
21868Asp His Pro Val Ile Gly Asp Leu Ala Ala Ala Ile Gln Gly Gly
7110 7115 7120
tca gta cgg cat tta cca ata act gca agc gag gtc gat gga cct
21913Ser Val Arg His Leu Pro Ile Thr Ala Ser Glu Val Asp Gly Pro
7125 7130 7135
gtt cag cag tcc ttc gcg caa aat cgc ttg tgg ttc cta gag cag
21958Val Gln Gln Ser Phe Ala Gln Asn Arg Leu Trp Phe Leu Glu Gln
7140 7145 7150
atg aat att gga gct act tgg tac atc gta ccg tta gca gtg cgt
22003Met Asn Ile Gly Ala Thr Trp Tyr Ile Val Pro Leu Ala Val Arg
7155 7160 7165
ctg tac ggc aca ctg cga gtt gag gct ctg aat att gcg ttg cgt
22048Leu Tyr Gly Thr Leu Arg Val Glu Ala Leu Asn Ile Ala Leu Arg
7170 7175 7180
acg att cag caa cgc cac gaa aca tta cga acg acc ttc gaa gaa
22093Thr Ile Gln Gln Arg His Glu Thr Leu Arg Thr Thr Phe Glu Glu
7185 7190 7195
cta aat ggg att gcc gtt caa cgt tgt gat tca acc tgc caa ggc
22138Leu Asn Gly Ile Ala Val Gln Arg Cys Asp Ser Thr Cys Gln Gly
7200 7205 7210
caa tta agg gtg gta gat tta gtc ggg cag ggg cca gat cgc tat
22183Gln Leu Arg Val Val Asp Leu Val Gly Gln Gly Pro Asp Arg Tyr
7215 7220 7225
aga gag att ctg gat gtc cag caa act aca cca ttc gag ctg agc
22228Arg Glu Ile Leu Asp Val Gln Gln Thr Thr Pro Phe Glu Leu Ser
7230 7235 7240
cag gag cct gga tgg agg gta gcg ctg ctt cgt ctg gga gat gac
22273Gln Glu Pro Gly Trp Arg Val Ala Leu Leu Arg Leu Gly Asp Asp
7245 7250 7255
gac cac gtc ctc tcc atc gtc atg cat cac atc atc tcc gac ggt
22318Asp His Val Leu Ser Ile Val Met His His Ile Ile Ser Asp Gly
7260 7265 7270
tgg tct gtg gac gtg ctg cta cgt gag ata ggt cag ttc tac tcg
22363Trp Ser Val Asp Val Leu Leu Arg Glu Ile Gly Gln Phe Tyr Ser
7275 7280 7285
gcc gcg ctc cgg ggg cag gac ccg ttg tcg cag ata agt cct ctg
22408Ala Ala Leu Arg Gly Gln Asp Pro Leu Ser Gln Ile Ser Pro Leu
7290 7295 7300
ccg atc cag tat cgt gac ttc gct ctc tgg cag aga caa gac gag
22453Pro Ile Gln Tyr Arg Asp Phe Ala Leu Trp Gln Arg Gln Asp Glu
7305 7310 7315
caa gtt gcg gag cat cag cgc cag ctg gag cat tgg aca gag cag
22498Gln Val Ala Glu His Gln Arg Gln Leu Glu His Trp Thr Glu Gln
7320 7325 7330
ttg gca gac agt tca ccc gcc gag ttg ttg agc gac cac ccg agg
22543Leu Ala Asp Ser Ser Pro Ala Glu Leu Leu Ser Asp His Pro Arg
7335 7340 7345
cca tcg att ctt tct ggc cag gcg ggc gct att ccc gtc aat gtt
22588Pro Ser Ile Leu Ser Gly Gln Ala Gly Ala Ile Pro Val Asn Val
7350 7355 7360
caa ggc tct ctg tat cag gcg ctt cgg gcg ttc tgc cgc gct cac
22633Gln Gly Ser Leu Tyr Gln Ala Leu Arg Ala Phe Cys Arg Ala His
7365 7370 7375
cag gtc acc tct ttc gta gtc ctg ctc acg gcg ttc cgc ata gca
22678Gln Val Thr Ser Phe Val Val Leu Leu Thr Ala Phe Arg Ile Ala
7380 7385 7390
cac tat cgt ctg acg ggt gcg gag gac gca acc att gga act ccc
22723His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro
7395 7400 7405
att gca aat cgc aac cgg cca gag ctc gag aac atg atc ggt ttc
22768Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Phe
7410 7415 7420
ttc gtc aat aca caa tgc atg cgc atc gtc att ggc agt gac gac
22813Phe Val Asn Thr Gln Cys Met Arg Ile Val Ile Gly Ser Asp Asp
7425 7430 7435
aca ttt gaa ggg ctg gtg cag caa gta cgc tcg ata act gca gct
22858Thr Phe Glu Gly Leu Val Gln Gln Val Arg Ser Ile Thr Ala Ala
7440 7445 7450
gcc cac gag aac cag gac gtt cca ttc gag cgc atc gtg tca gca
22903Ala His Glu Asn Gln Asp Val Pro Phe Glu Arg Ile Val Ser Ala
7455 7460 7465
ctg ctt ccc ggt tct aga gac aca tca cgc aat cct ctg gtt cag
22948Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln
7470 7475 7480
ctc atg ttt gct gtc cac tcg caa aga aac ctt ggt cag atc agt
22993Leu Met Phe Ala Val His Ser Gln Arg Asn Leu Gly Gln Ile Ser
7485 7490 7495
cta gaa ggc ctg cag ggt gaa ttg ctg gga gtg gca gcg act acg
23038Leu Glu Gly Leu Gln Gly Glu Leu Leu Gly Val Ala Ala Thr Thr
7500 7505 7510
aga ttc gat gta gag ttc cat ctc ttc caa gat gac gac aag ctc
23083Arg Phe Asp Val Glu Phe His Leu Phe Gln Asp Asp Asp Lys Leu
7515 7520 7525
agc ggc aac gtg ctc ttc gcg acc gag ctc ttc gag cag aag act
23128Ser Gly Asn Val Leu Phe Ala Thr Glu Leu Phe Glu Gln Lys Thr
7530 7535 7540
atg caa ggc atg gtc gac gtg ttc cag gaa gtg ctc agc cgg ggc
23173Met Gln Gly Met Val Asp Val Phe Gln Glu Val Leu Ser Arg Gly
7545 7550 7555
ctt gag cag ccc cag ata cct ctg gcg acc ctc ccg ctc acg cac
23218Leu Glu Gln Pro Gln Ile Pro Leu Ala Thr Leu Pro Leu Thr His
7560 7565 7570
gga ctg gag gag ctc agg acc atg ggt ctt ctc gac gtg gag aag
23263Gly Leu Glu Glu Leu Arg Thr Met Gly Leu Leu Asp Val Glu Lys
7575 7580 7585
aca gac tac cct cga gag tcg agc gtg gtg gac gtg ttc cgt gag
23308Thr Asp Tyr Pro Arg Glu Ser Ser Val Val Asp Val Phe Arg Glu
7590 7595 7600
caa gcg gct gcc tgc tcc gag gcg att gcg gtc aaa gac tcg tcg
23353Gln Ala Ala Ala Cys Ser Glu Ala Ile Ala Val Lys Asp Ser Ser
7605 7610 7615
gcg cag ctc acc tac tcg gag ctc gat cga cag tcg gac gag ctt
23398Ala Gln Leu Thr Tyr Ser Glu Leu Asp Arg Gln Ser Asp Glu Leu
7620 7625 7630
gcc ggc tgg ctg cgc cag caa cgt ctt cct gcg gag tcg ttg gtt
23443Ala Gly Trp Leu Arg Gln Gln Arg Leu Pro Ala Glu Ser Leu Val
7635 7640 7645
gca gtg ctg gca ccc agg tcg tgc cag acc att gtc gcg ttc ctg
23488Ala Val Leu Ala Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu
7650 7655 7660
ggc atc ctc aag gcg aat ctg gca tac ctg ccg cta gac gtc aac
23533Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn
7665 7670 7675
gtg ccc gct act cgc ctc gag tcg ata ctg tct gcc gtc ggc ggc
23578Val Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser Ala Val Gly Gly
7680 7685 7690
cgg aag ctg gtc ttg ctt gga gct gac gtg gcc gac cct ggc ctt
23623Arg Lys Leu Val Leu Leu Gly Ala Asp Val Ala Asp Pro Gly Leu
7695 7700 7705
cgc ctg gcg gat gtg gag ctc gtg cgg atc ggc gac aca ctc ggc
23668Arg Leu Ala Asp Val Glu Leu Val Arg Ile Gly Asp Thr Leu Gly
7710 7715 7720
cgc tgt gta ccc ggg gcg ccc ggc gac aac gag gca cct gtg gtg
23713Arg Cys Val Pro Gly Ala Pro Gly Asp Asn Glu Ala Pro Val Val
7725 7730 7735
cag cct tct gcc aca agc ctt gcc tac gtc atc ttc act tcc ggc
23758Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly
7740 7745 7750
tcg acc ggc aag ccg aag ggt gtc atg gtc gag cac cgg ggt gta
23803Ser Thr Gly Lys Pro Lys Gly Val Met Val Glu His Arg Gly Val
7755 7760 7765
gtg cga ctt gtc aag cag agc aat gtt gtc tac cat ctc ccg tcc
23848Val Arg Leu Val Lys Gln Ser Asn Val Val Tyr His Leu Pro Ser
7770 7775 7780
aca tct cgc gtg gcc cac ctg tcg aat ctc gcc ttt gat gcc tcg
23893Thr Ser Arg Val Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ser
7785 7790 7795
gcg tgg gag atc tat gcg gca ctg ctt aat ggc ggt aca ctc atc
23938Ala Trp Glu Ile Tyr Ala Ala Leu Leu Asn Gly Gly Thr Leu Ile
7800 7805 7810
tgc att gac tat ttc aca act cta gac tgc tct gct ctc ggc gcc
23983Cys Ile Asp Tyr Phe Thr Thr Leu Asp Cys Ser Ala Leu Gly Ala
7815 7820 7825
aaa ttc atc aag gag aag atc gtc gcg acc atg att ccg cca gcg
24028Lys Phe Ile Lys Glu Lys Ile Val Ala Thr Met Ile Pro Pro Ala
7830 7835 7840
ctt ctg aag caa tgt ctg gcg atc ttc ccg acc gct ctt agt gaa
24073Leu Leu Lys Gln Cys Leu Ala Ile Phe Pro Thr Ala Leu Ser Glu
7845 7850 7855
ctg gtc ctg ctg ttt gct gcc gga gat cga ttc agc agt ggc gat
24118Leu Val Leu Leu Phe Ala Ala Gly Asp Arg Phe Ser Ser Gly Asp
7860 7865 7870
gcc gtc gaa gtg cag cgc cac acc aaa ggc gct gtt tgt aac gcg
24163Ala Val Glu Val Gln Arg His Thr Lys Gly Ala Val Cys Asn Ala
7875 7880 7885
tac gga ccg aca gaa aac acc att ctt agt acg atc tac gaa gtc
24208Tyr Gly Pro Thr Glu Asn Thr Ile Leu Ser Thr Ile Tyr Glu Val
7890 7895 7900
aag cag aat gag aac ttc ccg aac ggt gtg cct atc ggc cgc gct
24253Lys Gln Asn Glu Asn Phe Pro Asn Gly Val Pro Ile Gly Arg Ala
7905 7910 7915
gtg agc aac tca ggg gca tat gtc atg gac ccg cag cag caa ctg
24298Val Ser Asn Ser Gly Ala Tyr Val Met Asp Pro Gln Gln Gln Leu
7920 7925 7930
gtg cct ctc ggg gtg atg ggc gag ctc gtc gtc acc ggc gac ggc
24343Val Pro Leu Gly Val Met Gly Glu Leu Val Val Thr Gly Asp Gly
7935 7940 7945
ctg gcc cgt ggt tac acc gac ccg tca ctg gat gcg gac cgc ttt
24388Leu Ala Arg Gly Tyr Thr Asp Pro Ser Leu Asp Ala Asp Arg Phe
7950 7955 7960
gtg cag gtc tcc gtc aac ggg cag ctc gtg aga gcg tac cga aca
24433Val Gln Val Ser Val Asn Gly Gln Leu Val Arg Ala Tyr Arg Thr
7965 7970 7975
ggc gat cgc gtg cgc tgc agg cct tgc gat ggc cag atc gag ttc
24478Gly Asp Arg Val Arg Cys Arg Pro Cys Asp Gly Gln Ile Glu Phe
7980 7985 7990
ttt gga cgt atg gac cgg caa gtc aag atc cga gga cat cgc atc
24523Phe Gly Arg Met Asp Arg Gln Val Lys Ile Arg Gly His Arg Ile
7995 8000 8005
gag ctc gca gag gta gag cat gcg gtg ctt ggc ttg gaa gac gtg
24568Glu Leu Ala Glu Val Glu His Ala Val Leu Gly Leu Glu Asp Val
8010 8015 8020
caa gac gct gcc gtt atc gca ttt gac aat gtg gac agc gaa gag
24613Gln Asp Ala Ala Val Ile Ala Phe Asp Asn Val Asp Ser Glu Glu
8025 8030 8035
cca gaa atg gtt ggg ttt gtc act att acc gaa gac aat cct gtc
24658Pro Glu Met Val Gly Phe Val Thr Ile Thr Glu Asp Asn Pro Val
8040 8045 8050
cgt gag gac gaa acc agc ggt caa gta gaa gac tgg gcg aac cac
24703Arg Glu Asp Glu Thr Ser Gly Gln Val Glu Asp Trp Ala Asn His
8055 8060 8065
ttc gag ata agt acc tac acc gat atc gcg gcg atc gat cag ggt
24748Phe Glu Ile Ser Thr Tyr Thr Asp Ile Ala Ala Ile Asp Gln Gly
8070 8075 8080
agc att gga agt gac ttt gta ggt tgg act tct atg tac gac gga
24793Ser Ile Gly Ser Asp Phe Val Gly Trp Thr Ser Met Tyr Asp Gly
8085 8090 8095
agc gag atc gac aag gca gag atg caa gaa tgg ctt gcc gat acc
24838Ser Glu Ile Asp Lys Ala Glu Met Gln Glu Trp Leu Ala Asp Thr
8100 8105 8110
atg gcc tct atg ctc gac ggg cag gcg ccg ggc aat gtg tta gag
24883Met Ala Ser Met Leu Asp Gly Gln Ala Pro Gly Asn Val Leu Glu
8115 8120 8125
ata ggt aca ggc act ggc atg gtc ctc ttc aat ctc ggc gac gga
24928Ile Gly Thr Gly Thr Gly Met Val Leu Phe Asn Leu Gly Asp Gly
8130 8135 8140
ctg cag agc tat gtc ggc ctc gaa cca tca aga tcg gcg gcc gct
24973Leu Gln Ser Tyr Val Gly Leu Glu Pro Ser Arg Ser Ala Ala Ala
8145 8150 8155
ttt gtc aac cag acg att aag tcg ctc ccc acc ctt gct ggc aac
25018Phe Val Asn Gln Thr Ile Lys Ser Leu Pro Thr Leu Ala Gly Asn
8160 8165 8170
gct gaa gta cac att ggc act gcg acc gac gtg gcc cgt cta gat
25063Ala Glu Val His Ile Gly Thr Ala Thr Asp Val Ala Arg Leu Asp
8175 8180 8185
ggc ctc cgc ccc gac tta gtg gta gtc aat tcg gta gtc cag tac
25108Gly Leu Arg Pro Asp Leu Val Val Val Asn Ser Val Val Gln Tyr
8190 8195 8200
ttc cca tca cca gag tac cta atg gaa gtc gtg gag gct ctt gca
25153Phe Pro Ser Pro Glu Tyr Leu Met Glu Val Val Glu Ala Leu Ala
8205 8210 8215
cgt ctg ccg ggc gtc gag cga att ttc ttc gga gac gta cgt tcg
25198Arg Leu Pro Gly Val Glu Arg Ile Phe Phe Gly Asp Val Arg Ser
8220 8225 8230
tac gcc atc aac aga gat ttc ctg gct gcc aga gct cta cac gaa
25243Tyr Ala Ile Asn Arg Asp Phe Leu Ala Ala Arg Ala Leu His Glu
8235 8240 8245
ctt ggc gac aga gcg act aag cac gag att cgg cga aag atg cta
25288Leu Gly Asp Arg Ala Thr Lys His Glu Ile Arg Arg Lys Met Leu
8250 8255 8260
gag atg gaa gaa cgc gaa gag gag ctg ctc gtc gac cca gct ttc
25333Glu Met Glu Glu Arg Glu Glu Glu Leu Leu Val Asp Pro Ala Phe
8265 8270 8275
ttc acc atg ttg acc agc agt ctc cct ggc ctg att cag cat gtc
25378Phe Thr Met Leu Thr Ser Ser Leu Pro Gly Leu Ile Gln His Val
8280 8285 8290
gag atc ttg ccg aag ctg atg aga gcc act aat gag ctc agc gcg
25423Glu Ile Leu Pro Lys Leu Met Arg Ala Thr Asn Glu Leu Ser Ala
8295 8300 8305
tat cga tac act gct gta gta cac gtg tgc cgt gcc ggt caa gag
25468Tyr Arg Tyr Thr Ala Val Val His Val Cys Arg Ala Gly Gln Glu
8310 8315 8320
cct cgt tcc gtg cat acg atc gac gac gat gcc tgg gtg aat ctt
25513Pro Arg Ser Val His Thr Ile Asp Asp Asp Ala Trp Val Asn Leu
8325 8330 8335
gga gct tct cgg ttg agt cgc cct acc ctt tca agc ctt ttg caa
25558Gly Ala Ser Arg Leu Ser Arg Pro Thr Leu Ser Ser Leu Leu Gln
8340 8345 8350
act tcc gag ggc gca tcg gcc gtc gca gta agc aat att cct tac
25603Thr Ser Glu Gly Ala Ser Ala Val Ala Val Ser Asn Ile Pro Tyr
8355 8360 8365
agc aag acc atc aca gag cga gcg ctc gtt agt gcg ctc gat gag
25648Ser Lys Thr Ile Thr Glu Arg Ala Leu Val Ser Ala Leu Asp Glu
8370 8375 8380
gat gat atg caa gac tca tcg gac tgg ctg ctg gcc gtg cgc gag
25693Asp Asp Met Gln Asp Ser Ser Asp Trp Leu Leu Ala Val Arg Glu
8385 8390 8395
aca ggc aga tct tgt tcc tcc ttc tcc gca aca gac ctt gtc gag
25738Thr Gly Arg Ser Cys Ser Ser Phe Ser Ala Thr Asp Leu Val Glu
8400 8405 8410
ctt gct cga gag acg ggc tgg cgt gtg gag ctc agc tgg gca cga
25783Leu Ala Arg Glu Thr Gly Trp Arg Val Glu Leu Ser Trp Ala Arg
8415 8420 8425
cag tac tca cag aaa ggc gca ctc gat gct gtc ttc cac aga cac
25828Gln Tyr Ser Gln Lys Gly Ala Leu Asp Ala Val Phe His Arg His
8430 8435 8440
cct gtt tcc gct ggg agc ggg cgt gtc atg ttc cag ttt cca gtt
25873Pro Val Ser Ala Gly Ser Gly Arg Val Met Phe Gln Phe Pro Val
8445 8450 8455
gag acc gaa gat cga ccg cac atc tca cgc acg aac cga cct tta
25918Glu Thr Glu Asp Arg Pro His Ile Ser Arg Thr Asn Arg Pro Leu
8460 8465 8470
cag cga ttg cag aag aag cga acc gag aca cat gtt cat gag cag
25963Gln Arg Leu Gln Lys Lys Arg Thr Glu Thr His Val His Glu Gln
8475 8480 8485
ttg cgg gct ttg ctt cca cga tac atg gtt cct acg cgg att gtg
26008Leu Arg Ala Leu Leu Pro Arg Tyr Met Val Pro Thr Arg Ile Val
8490 8495 8500
gcg ctt gat aag ctg ccc gtc aat gca aac ggc aag gtt gat cgt
26053Ala Leu Asp Lys Leu Pro Val Asn Ala Asn Gly Lys Val Asp Arg
8505 8510 8515
caa cag ctc gct agg aca gcc cag gtt ctc cca gcg agc aag gcg
26098Gln Gln Leu Ala Arg Thr Ala Gln Val Leu Pro Ala Ser Lys Ala
8520 8525 8530
ccg tct gca tgc gtg gcc cca cgc aac gaa ttg gaa atg aca ctg
26143Pro Ser Ala Cys Val Ala Pro Arg Asn Glu Leu Glu Met Thr Leu
8535 8540 8545
tgt gaa gag ttc tcg cag gtt ctt ggc gtc gag gtc ggc att act
26188Cys Glu Glu Phe Ser Gln Val Leu Gly Val Glu Val Gly Ile Thr
8550 8555 8560
gac aat ttc ttc cac ctg ggt ggc cac tct ctc atg gca aca aag
26233Asp Asn Phe Phe His Leu Gly Gly His Ser Leu Met Ala Thr Lys
8565 8570 8575
ttc gcc gct cgt atc agc cgc cgg ctg aat gct atc gtt tcg gtc
26278Phe Ala Ala Arg Ile Ser Arg Arg Leu Asn Ala Ile Val Ser Val
8580 8585 8590
aag aat gtc ttc gac cac ccc gta cct atg gat ctt gca gcg aca
26323Lys Asn Val Phe Asp His Pro Val Pro Met Asp Leu Ala Ala Thr
8595 8600 8605
atc caa gaa ggc tca aag ctt cat act cca atc cct cgc acg gct
26368Ile Gln Glu Gly Ser Lys Leu His Thr Pro Ile Pro Arg Thr Ala
8610 8615 8620
tac agc ggt cct gtc gaa cag tct ttc gca caa gga cgt ctt tgg
26413Tyr Ser Gly Pro Val Glu Gln Ser Phe Ala Gln Gly Arg Leu Trp
8625 8630 8635
ttc ctt gac caa ttc aat cct agc tcg att ggg tat gtg atg cct
26458Phe Leu Asp Gln Phe Asn Pro Ser Ser Ile Gly Tyr Val Met Pro
8640 8645 8650
ttc gct gcg cgt ctt cat ggt caa cta caa atc gaa gcg ctc aca
26503Phe Ala Ala Arg Leu His Gly Gln Leu Gln Ile Glu Ala Leu Thr
8655 8660 8665
gca gca ttg ttc gct ttg gaa cag cga cat gag atc ctg cga aca
26548Ala Ala Leu Phe Ala Leu Glu Gln Arg His Glu Ile Leu Arg Thr
8670 8675 8680
acg ttg gac gca cac gat ggt gta ggc atg cag atc gtt cac gcg
26593Thr Leu Asp Ala His Asp Gly Val Gly Met Gln Ile Val His Ala
8685 8690 8695
gaa cat ccg caa cag ttg aga atc att gat gtg tca gca aag gcg
26638Glu His Pro Gln Gln Leu Arg Ile Ile Asp Val Ser Ala Lys Ala
8700 8705 8710
tcg agc agt tat gct cag aca ctg cgt gac gag cag gcg tca cct
26683Ser Ser Ser Tyr Ala Gln Thr Leu Arg Asp Glu Gln Ala Ser Pro
8715 8720 8725
ttc gac cta agc aag gaa cca ggt tgg aga gtc tcg ttg ctg cag
26728Phe Asp Leu Ser Lys Glu Pro Gly Trp Arg Val Ser Leu Leu Gln
8730 8735 8740
ctc agt gag ata gat tat gtt ctt tcc att gta atg cat cac acc
26773Leu Ser Glu Ile Asp Tyr Val Leu Ser Ile Val Met His His Thr
8745 8750 8755
atc tat gac ggt tgg tct ctc gac gta ctc cgg cgg gag cta agt
26818Ile Tyr Asp Gly Trp Ser Leu Asp Val Leu Arg Arg Glu Leu Ser
8760 8765 8770
cag ttt tat gcc gct gcc atc cgt ggt cga gaa cct cta tcg aca
26863Gln Phe Tyr Ala Ala Ala Ile Arg Gly Arg Glu Pro Leu Ser Thr
8775 8780 8785
atc gag cca ttg cct atc caa tac cgc gac ttt tct gtc tgg caa
26908Ile Glu Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ser Val Trp Gln
8790 8795 8800
aag cag gaa gac caa gtc gca gag cat cga cga cag ctc cat tat
26953Lys Gln Glu Asp Gln Val Ala Glu His Arg Arg Gln Leu His Tyr
8805 8810 8815
tgg ata gag cag cta gat ggc agc tct cct gct gag ttc cta aac
26998Trp Ile Glu Gln Leu Asp Gly Ser Ser Pro Ala Glu Phe Leu Asn
8820 8825 8830
gat aaa cca cgg cct acg ttg ctt tct ggc aag gca gga gtt gtg
27043Asp Lys Pro Arg Pro Thr Leu Leu Ser Gly Lys Ala Gly Val Val
8835 8840 8845
gaa att gct gtg aag ggc act gta tat caa cgt ctg cta gag ttc
27088Glu Ile Ala Val Lys Gly Thr Val Tyr Gln Arg Leu Leu Glu Phe
8850 8855 8860
tgc agg ctt cat cag gtc acc tcg ttc atg gtg ctg ctt gcg gca
27133Cys Arg Leu His Gln Val Thr Ser Phe Met Val Leu Leu Ala Ala
8865 8870 8875
ttc cga gcg aca cac tat cgt ctg aca ggc aca gag gac gcg act
27178Phe Arg Ala Thr His Tyr Arg Leu Thr Gly Thr Glu Asp Ala Thr
8880 8885 8890
gtc gga aca ccc atc gcc aat cgc aat cga cct gag ctg gag aac
27223Val Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn
8895 8900 8905
atg att gga ttg ttc gtg aat act cag tgt ata cgc ctc aag atc
27268Met Ile Gly Leu Phe Val Asn Thr Gln Cys Ile Arg Leu Lys Ile
8910 8915 8920
gag gac aat gat act ctc gag gag cta gta cag cac gtt cgt gcc
27313Glu Asp Asn Asp Thr Leu Glu Glu Leu Val Gln His Val Arg Ala
8925 8930 8935
acg atc aca gca tca atc tcg aac cag gat gta ccc ttt gaa cag
27358Thr Ile Thr Ala Ser Ile Ser Asn Gln Asp Val Pro Phe Glu Gln
8940 8945 8950
gta gtg tct gca ttg cta cca gga tca cgc gac acc tct agg aac
27403Val Val Ser Ala Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn
8955 8960 8965
cca cta gtt cag ctg act ttt gcg gtg cat tct cag cga aat ttg
27448Pro Leu Val Gln Leu Thr Phe Ala Val His Ser Gln Arg Asn Leu
8970 8975 8980
gct gac att cag cta gaa aac gtg gag acc aat gct atg cca att
27493Ala Asp Ile Gln Leu Glu Asn Val Glu Thr Asn Ala Met Pro Ile
8985 8990 8995
tgc ccc tcg aca cgt ttc gac gct gaa ttc cac ctc ttc caa gag
27538Cys Pro Ser Thr Arg Phe Asp Ala Glu Phe His Leu Phe Gln Glu
9000 9005 9010
gag aat atg cta agc gga agg gtg ctg ttt tca gac gat ctt ttc
27583Glu Asn Met Leu Ser Gly Arg Val Leu Phe Ser Asp Asp Leu Phe
9015 9020 9025
gag cag aag act atg caa ggc atg gtc gac gtg ttc cag gaa gtg
27628Glu Gln Lys Thr Met Gln Gly Met Val Asp Val Phe Gln Glu Val
9030 9035 9040
ctc agc cgg ggc ctt gag cag ccc cag ata cct ctg gcg acc ctc
27673Leu Ser Arg Gly Leu Glu Gln Pro Gln Ile Pro Leu Ala Thr Leu
9045 9050 9055
ccg ctc acg cac gga ctg gag gag ctc agg acc atg ggt ctt ctc
27718Pro Leu Thr His Gly Leu Glu Glu Leu Arg Thr Met Gly Leu Leu
9060 9065 9070
gac gtg gag aag aca gac tac cct cga gag tcg agc gtg gtg gac
27763Asp Val Glu Lys Thr Asp Tyr Pro Arg Glu Ser Ser Val Val Asp
9075 9080 9085
gtg ttc cgt gag caa gcg gct gcc tgc tcc gag gcg att gcg gtc
27808Val Phe Arg Glu Gln Ala Ala Ala Cys Ser Glu Ala Ile Ala Val
9090 9095 9100
aaa gac tcg tcg gcg cag ctc acc tac tcg gag ctc gat cga cag
27853Lys Asp Ser Ser Ala Gln Leu Thr Tyr Ser Glu Leu Asp Arg Gln
9105 9110 9115
tcg gac gag ctt gcc ggc tgg ctg cgc cag caa cgt ctt cct gcg
27898Ser Asp Glu Leu Ala Gly Trp Leu Arg Gln Gln Arg Leu Pro Ala
9120 9125 9130
gag tcg ttg gtt gca gtg ctg gca ccc agg tcg tgc cag acc att
27943Glu Ser Leu Val Ala Val Leu Ala Pro Arg Ser Cys Gln Thr Ile
9135 9140 9145
gtc gcg ttc ctg ggc atc ctc aag gcg aat ctg gca tac ctg ccg
27988Val Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro
9150 9155 9160
cta gac gtc aac gtg ccc gct act cgc ctc gag tcg ata ctg tct
28033Leu Asp Val Asn Val Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser
9165 9170 9175
gcc gtc ggc ggc cgg aag ctg gtc ttg ctt gga gct gac gtg gcc
28078Ala Val Gly Gly Arg Lys Leu Val Leu Leu Gly Ala Asp Val Ala
9180 9185 9190
gac cct ggc ctt cgc ctg gcg gat gtg gag ctc gtg cgg atc ggc
28123Asp Pro Gly Leu Arg Leu Ala Asp Val Glu Leu Val Arg Ile Gly
9195 9200 9205
gac aca ctc ggc cgc tgt gta ccc ggg gcg ccc ggc gac aac gag
28168Asp Thr Leu Gly Arg Cys Val Pro Gly Ala Pro Gly Asp Asn Glu
9210 9215 9220
gca cct gtg gtg cag cct tct gcc aca agc ctt gcc tac gtc atc
28213Ala Pro Val Val Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile
9225 9230 9235
ttc act tcc ggc tcg acc ggc aag ccg aag ggt gtc atg gtc gag
28258Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly Val Met Val Glu
9240 9245 9250
cac cgg ggt gta gtg cga ctt gtc aag cag agc aat gtt gtc tac
28303His Arg Gly Val Val Arg Leu Val Lys Gln Ser Asn Val Val Tyr
9255 9260 9265
cat ctc ccg tcc aca tct cgc gtg gcc cac ctg tcg aat ctc gcc
28348His Leu Pro Ser Thr Ser Arg Val Ala His Leu Ser Asn Leu Ala
9270 9275 9280
ttt gat gcc tcg gcg tgg gag atc tat gcg gca ctg ctt aat ggc
28393Phe Asp Ala Ser Ala Trp Glu Ile Tyr Ala Ala Leu Leu Asn Gly
9285 9290 9295
ggt aca ctc atc tgc att gac tat ttc acc atc ata gac gct cgc
28438Gly Thr Leu Ile Cys Ile Asp Tyr Phe Thr Ile Ile Asp Ala Arg
9300 9305 9310
gca ctt ggc gtt atc ttt gcg caa caa agt atc aac gca acc atg
28483Ala Leu Gly Val Ile Phe Ala Gln Gln Ser Ile Asn Ala Thr Met
9315 9320 9325
ctg tca cct cta ctc ctc aaa caa ttt ttg tca gat gca cca ttc
28528Leu Ser Pro Leu Leu Leu Lys Gln Phe Leu Ser Asp Ala Pro Phe
9330 9335 9340
gtg ctg cga tct ctg cat gcc ctt tat cta ggg ggg gac aga ctt
28573Val Leu Arg Ser Leu His Ala Leu Tyr Leu Gly Gly Asp Arg Leu
9345 9350 9355
cag ggt cgt gac gca atc cag gct tgt cgt gta ggt tgc gca ttt
28618Gln Gly Arg Asp Ala Ile Gln Ala Cys Arg Val Gly Cys Ala Phe
9360 9365 9370
gtc atc aat gcc tat ggc cca aca gag aat tct gtc atc agt act
28663Val Ile Asn Ala Tyr Gly Pro Thr Glu Asn Ser Val Ile Ser Thr
9375 9380 9385
act tac aca ctt gtg aag gga aat gcg gac ttc ccg aac ggt gtg
28708Thr Tyr Thr Leu Val Lys Gly Asn Ala Asp Phe Pro Asn Gly Val
9390 9395 9400
cct atc ggc cgc gct gtg agc aac tca ggg gca tat gtc atg gac
28753Pro Ile Gly Arg Ala Val Ser Asn Ser Gly Ala Tyr Val Met Asp
9405 9410 9415
ccg cag cag caa ctg gtg cct ctc ggg gtg atg ggc gag ctc gtc
28798Pro Gln Gln Gln Leu Val Pro Leu Gly Val Met Gly Glu Leu Val
9420 9425 9430
gtc acc ggc gac ggc ctg gcc cgt ggt tac acc gac ccg tca ctg
28843Val Thr Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Ser Leu
9435 9440 9445
gat gcg gac cgc ttt gtg cag gtc tcc gtc aac ggg cag ctc gtg
28888Asp Ala Asp Arg Phe Val Gln Val Ser Val Asn Gly Gln Leu Val
9450 9455 9460
aga gcg tac cga aca ggc gat cgc gtg cgc tgc agg cct tgc gat
28933Arg Ala Tyr Arg Thr Gly Asp Arg Val Arg Cys Arg Pro Cys Asp
9465 9470 9475
ggc cag atc gag ttc ttt gga cgt atg gac cgg caa gtc aag atc
28978Gly Gln Ile Glu Phe Phe Gly Arg Met Asp Arg Gln Val Lys Ile
9480 9485 9490
cga gga cat cgc atc gag ctc gca gag gta gag cat gcg gtg ctt
29023Arg Gly His Arg Ile Glu Leu Ala Glu Val Glu His Ala Val Leu
9495 9500 9505
ggc ttg gaa gac gtg caa gac gct gcc gtt ctc ata gct caa aca
29068Gly Leu Glu Asp Val Gln Asp Ala Ala Val Leu Ile Ala Gln Thr
9510 9515 9520
gcc gaa aat gaa gag cta gtt ggc ttc ttc acg ctt cga caa acc
29113Ala Glu Asn Glu Glu Leu Val Gly Phe Phe Thr Leu Arg Gln Thr
9525 9530 9535
cag gct gtg cag tca aat ggt gcc gct ggt gtt gtg cca gag cac
29158Gln Ala Val Gln Ser Asn Gly Ala Ala Gly Val Val Pro Glu His
9540 9545 9550
agc gac tcc gag ctg gcg caa tcc tgc tct tgc act caa acg gag
29203Ser Asp Ser Glu Leu Ala Gln Ser Cys Ser Cys Thr Gln Thr Glu
9555 9560 9565
cgt cga gtc cgc aac aga ttg caa tcc tgt ctt cct cgc tac atg
29248Arg Arg Val Arg Asn Arg Leu Gln Ser Cys Leu Pro Arg Tyr Met
9570 9575 9580
gtt ccg tcg cga atg gtc ctt ttg gat cga ctg cct gtc aac ccc
29293Val Pro Ser Arg Met Val Leu Leu Asp Arg Leu Pro Val Asn Pro
9585 9590 9595
aat ggt aaa gtt gat cga caa gag ctc acg agg cgc gct cag gat
29338Asn Gly Lys Val Asp Arg Gln Glu Leu Thr Arg Arg Ala Gln Asp
9600 9605 9610
ctc cca ata agc gag tca tcc cca gtg cac gtc aaa ccg cgt act
29383Leu Pro Ile Ser Glu Ser Ser Pro Val His Val Lys Pro Arg Thr
9615 9620 9625
gaa ctg gaa agg tcg ctg tgc gag gag ttc gcc gat gtt ata ggt
29428Glu Leu Glu Arg Ser Leu Cys Glu Glu Phe Ala Asp Val Ile Gly
9630 9635 9640
ttg gaa gtc ggc gtt acc gat aat ttc ttc gac cta ggc ggg cac
29473Leu Glu Val Gly Val Thr Asp Asn Phe Phe Asp Leu Gly Gly His
9645 9650 9655
tct ctc atg gcg atg aaa ctc gca gct cgc atc agc cgt cgt tcg
29518Ser Leu Met Ala Met Lys Leu Ala Ala Arg Ile Ser Arg Arg Ser
9660 9665 9670
aat gca cat ata tca gtc aag gac att ttc gac cac ccg ctg att
29563Asn Ala His Ile Ser Val Lys Asp Ile Phe Asp His Pro Leu Ile
9675 9680 9685
gca gat ctc gca atg aaa att cgg gaa ggc tcc gat ctg cac act
29608Ala Asp Leu Ala Met Lys Ile Arg Glu Gly Ser Asp Leu His Thr
9690 9695 9700
cca att ccc cac agg atg tac gtt gga cct atc cag cta tca ttc
29653Pro Ile Pro His Arg Met Tyr Val Gly Pro Ile Gln Leu Ser Phe
9705 9710 9715
gca cag gga cgc ttg tgg ttc ctc gac caa ttg aat ttg ggc gca
29698Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln Leu Asn Leu Gly Ala
9720 9725 9730
tcg tgg tac gtc atg cca ctt gct atg cgc ctc caa ggc tcg ctc
29743Ser Trp Tyr Val Met Pro Leu Ala Met Arg Leu Gln Gly Ser Leu
9735 9740 9745
cag ctc gac gcg tta gag act gca ctg ttt gct atc gag cag cga
29788Gln Leu Asp Ala Leu Glu Thr Ala Leu Phe Ala Ile Glu Gln Arg
9750 9755 9760
cac gaa acc tta cgg atg aca ttt gca gaa caa gac gga gta gct
29833His Glu Thr Leu Arg Met Thr Phe Ala Glu Gln Asp Gly Val Ala
9765 9770 9775
gta caa gta gtg cat gca gcc cac tac aaa cac atc aag atg atc
29878Val Gln Val Val His Ala Ala His Tyr Lys His Ile Lys Met Ile
9780 9785 9790
gac aaa cca ctt aga cag aag att gac gtc ctg aag atg ctg gaa
29923Asp Lys Pro Leu Arg Gln Lys Ile Asp Val Leu Lys Met Leu Glu
9795 9800 9805
gaa gaa cgg acg act ccc ttc gag ctg agc cgc gag cct gga tgg
29968Glu Glu Arg Thr Thr Pro Phe Glu Leu Ser Arg Glu Pro Gly Trp
9810 9815 9820
agg gta gcg ctg ctg cgt ctg gga gat gac gac cac gtc ctc tcc
30013Arg Val Ala Leu Leu Arg Leu Gly Asp Asp Asp His Val Leu Ser
9825 9830 9835
atc gtc atg cat cac atc atc tcc gac ggt tgg tct gtg gac gtg
30058Ile Val Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp Val
9840 9845 9850
ctg cgc cac gag cta ggt cag ttc tac tcg gcc gcg ctc cgg ggg
30103Leu Arg His Glu Leu Gly Gln Phe Tyr Ser Ala Ala Leu Arg Gly
9855 9860 9865
cag gac ccg ttg tcg cag ata agt cct ctg ccg atc cag tat cgt
30148Gln Asp Pro Leu Ser Gln Ile Ser Pro Leu Pro Ile Gln Tyr Arg
9870 9875 9880
gac ttc gct ctc tgg cag aga caa gac gag caa gtt gcg gag cat
30193Asp Phe Ala Leu Trp Gln Arg Gln Asp Glu Gln Val Ala Glu His
9885 9890 9895
cag cgc cag ctg gag cat tgg aca gag cag ttg gca gac agt tca
30238Gln Arg Gln Leu Glu His Trp Thr Glu Gln Leu Ala Asp Ser Ser
9900 9905 9910
ccc gcc gag ttg ttg agc gac cac ccg agg cca tcg att ctt tct
30283Pro Ala Glu Leu Leu Ser Asp His Pro Arg Pro Ser Ile Leu Ser
9915 9920 9925
ggc cag gcg ggc gct att ccc gtc aat gtt caa ggc tct ctg tat
30328Gly Gln Ala Gly Ala Ile Pro Val Asn Val Gln Gly Ser Leu Tyr
9930 9935 9940
cag gcg ctt cgg gcg ttc tgc cgc gct cac cag gtc acc tct ttc
30373Gln Ala Leu Arg Ala Phe Cys Arg Ala His Gln Val Thr Ser Phe
9945 9950 9955
gta gtc ctg ctc acg gcg ttc cgc ata gca cac tat cgt ctg acg
30418Val Val Leu Leu Thr Ala Phe Arg Ile Ala His Tyr Arg Leu Thr
9960 9965 9970
ggt gcg gag gac gca acc att gga act ccc att gca aat cgc aac
30463Gly Ala Glu Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn Arg Asn
9975 9980 9985
cgg cca gag ctc gag aac atg atc ggt ttc ttc gtc aat aca caa
30508Arg Pro Glu Leu Glu Asn Met Ile Gly Phe Phe Val Asn Thr Gln
9990 9995 10000
tgc atg cgc atc gtc att ggc agt gac gac aca ttt gaa ggg ctg
30553Cys Met Arg Ile Val Ile Gly Ser Asp Asp Thr Phe Glu Gly Leu
10005 10010 10015
gtg cag caa gta cgc tcg ata act gca gct gcc cac gag aac cag
30598Val Gln Gln Val Arg Ser Ile Thr Ala Ala Ala His Glu Asn Gln
10020 10025 10030
gac gtt cca ttc gag cgc atc gtg tca gca ctg ctt ccc ggt tct
30643Asp Val Pro Phe Glu Arg Ile Val Ser Ala Leu Leu Pro Gly Ser
10035 10040 10045
aga gac aca tca cgc aat cct ctg gtt cag ctc atg ttt gct gtc
30688Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Met Phe Ala Val
10050 10055 10060
cac tcg caa aga aac ctt ggt cag atc agt cta gaa ggc ctg cag
30733His Ser Gln Arg Asn Leu Gly Gln Ile Ser Leu Glu Gly Leu Gln
10065 10070 10075
ggt gaa ttg ctg gga gtg gca gcg act acg aga ttc gat gta gag
30778Gly Glu Leu Leu Gly Val Ala Ala Thr Thr Arg Phe Asp Val Glu
10080 10085 10090
ttc cat ctc ttc caa gat gac gac aag ctc agc ggc aac gtg ctc
30823Phe His Leu Phe Gln Asp Asp Asp Lys Leu Ser Gly Asn Val Leu
10095 10100 10105
ttc gcg acc gag ctc ttc gag cag aag act atg caa ggc atg gtc
30868Phe Ala Thr Glu Leu Phe Glu Gln Lys Thr Met Gln Gly Met Val
10110 10115 10120
gac gtg ttc cag gaa gtg ctc agc cgg ggc ctt gag cag ccc cag
30913Asp Val Phe Gln Glu Val Leu Ser Arg Gly Leu Glu Gln Pro Gln
10125 10130 10135
ata cct ctg gcg acc ctc ccg ctc acg cac gga ctg gag gag ctc
30958Ile Pro Leu Ala Thr Leu Pro Leu Thr His Gly Leu Glu Glu Leu
10140 10145 10150
agg acc atg ggt ctt ctc gac gtg gag aag aca gac tac cct cga
31003Arg Thr Met Gly Leu Leu Asp Val Glu Lys Thr Asp Tyr Pro Arg
10155 10160 10165
gag tcg agc gtg gtg gac gtg ttc cgt gag caa gcg gct gcc tgc
31048Glu Ser Ser Val Val Asp Val Phe Arg Glu Gln Ala Ala Ala Cys
10170 10175 10180
tcc gag gcg att gcg gtc aaa gac tcg tcg gcg cag ctc acc tac
31093Ser Glu Ala Ile Ala Val Lys Asp Ser Ser Ala Gln Leu Thr Tyr
10185 10190 10195
tcg gag ctc gat cga cag tcg gac gag ctt gcc ggc tgg ctg cgc
31138Ser Glu Leu Asp Arg Gln Ser Asp Glu Leu Ala Gly Trp Leu Arg
10200 10205 10210
cag caa cgt ctt cct gcg gag tcg ttg gtt gca gtg ctg gca ccc
31183Gln Gln Arg Leu Pro Ala Glu Ser Leu Val Ala Val Leu Ala Pro
10215 10220 10225
agg tcg tgc cag acc att gtc gcg ttc ctg ggc atc ctc aag gcg
31228Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Ile Leu Lys Ala
10230 10235 10240
aat ctg gca tac ctg ccg cta gac gtc aac gtg ccc gct act cgc
31273Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala Thr Arg
10245 10250 10255
ctc gag tcg ata ctg tct gcc gtc ggc ggc cgg aag ctg gtc ttg
31318Leu Glu Ser Ile Leu Ser Ala Val Gly Gly Arg Lys Leu Val Leu
10260 10265 10270
ctt gga gct gac gtg gcc gac cct ggc ctt cgc ctg gcg gat gtg
31363Leu Gly Ala Asp Val Ala Asp Pro Gly Leu Arg Leu Ala Asp Val
10275 10280 10285
gag ctc gtg cgg atc ggc gac aca ctc ggc cgc tgt gta ccc ggg
31408Glu Leu Val Arg Ile Gly Asp Thr Leu Gly Arg Cys Val Pro Gly
10290 10295 10300
gcg ccc ggc gac aac gag gca cct gtg gtg cag cct tct gcc aca
31453Ala Pro Gly Asp Asn Glu Ala Pro Val Val Gln Pro Ser Ala Thr
10305 10310 10315
agc ctt gcc tac gtc atc ttc act tcc ggc tcg acc ggc aag ccg
31498Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro
10320 10325 10330
aag ggt gtc atg gtc gag cac cgg ggt gta gtg cga ctt gtc aag
31543Lys Gly Val Met Val Glu His Arg Gly Val Val Arg Leu Val Lys
10335 10340 10345
cag agc aat gtt gtc tac cat ctc ccg tcc aca tct cgc gtg gcc
31588Gln Ser Asn Val Val Tyr His Leu Pro Ser Thr Ser Arg Val Ala
10350 10355 10360
cac ctg tcg aat ctc gcc ttt gat gcc tcg gcg tgg gag atc tat
31633His Leu Ser Asn Leu Ala Phe Asp Ala Ser Ala Trp Glu Ile Tyr
10365 10370 10375
gcg gca ctg ctt aat ggc ggt aca ctc atc tgc att gac tat ttc
31678Ala Ala Leu Leu Asn Gly Gly Thr Leu Ile Cys Ile Asp Tyr Phe
10380 10385 10390
aca act cta gac tgc tct gct ctc ggc gcc aaa ttc atc aag gag
31723Thr Thr Leu Asp Cys Ser Ala Leu Gly Ala Lys Phe Ile Lys Glu
10395 10400 10405
aag atc gtc gcg acc atg att ccg cca gcg ctt ctg aag caa tgt
31768Lys Ile Val Ala Thr Met Ile Pro Pro Ala Leu Leu Lys Gln Cys
10410 10415 10420
ctg gcg atc ttc ccg acc gct ctt agt gaa ctg gtc ctg ctg ttt
31813Leu Ala Ile Phe Pro Thr Ala Leu Ser Glu Leu Val Leu Leu Phe
10425 10430 10435
gct gcc gga gat cga ttc agc agt ggc gat gcc gtc gaa gtg cag
31858Ala Ala Gly Asp Arg Phe Ser Ser Gly Asp Ala Val Glu Val Gln
10440 10445 10450
cgc cac acc aaa ggc gct gtt tgt aac gcg tac gga ccg aca gaa
31903Arg His Thr Lys Gly Ala Val Cys Asn Ala Tyr Gly Pro Thr Glu
10455 10460 10465
aac acc att ctt agt acg atc tac gaa gtc aag cag aat gag aac
31948Asn Thr Ile Leu Ser Thr Ile Tyr Glu Val Lys Gln Asn Glu Asn
10470 10475 10480
ttc ccg aac ggt gtg cct atc ggc cgc gct gtg agc aac tca ggg
31993Phe Pro Asn Gly Val Pro Ile Gly Arg Ala Val Ser Asn Ser Gly
10485 10490 10495
gca tat gtc atg gac ccg cag cag caa ctg gtg cct ctc ggg gtg
32038Ala Tyr Val Met Asp Pro Gln Gln Gln Leu Val Pro Leu Gly Val
10500 10505 10510
atg ggc gag ctc gtc gtc acc ggc gac ggc ctg gcc cgt ggt tac
32083Met Gly Glu Leu Val Val Thr Gly Asp Gly Leu Ala Arg Gly Tyr
10515 10520 10525
acc gac ccg tca ctg gat gcg gac cgc ttt gtg cag gtc tcc gtc
32128Thr Asp Pro Ser Leu Asp Ala Asp Arg Phe Val Gln Val Ser Val
10530 10535 10540
aac ggg cag ctc gtg aga gcg tac cga aca ggc gat cgc gtg cgc
32173Asn Gly Gln Leu Val Arg Ala Tyr Arg Thr Gly Asp Arg Val Arg
10545 10550 10555
tgc agg cct tgc gat ggc cag atc gag ttc ttt gga cgt atg gac
32218Cys Arg Pro Cys Asp Gly Gln Ile Glu Phe Phe Gly Arg Met Asp
10560 10565 10570
cgg caa gtc aag atc cga gga cat cgc atc gag ctc gca gag gta
32263Arg Gln Val Lys Ile Arg Gly His Arg Ile Glu Leu Ala Glu Val
10575 10580 10585
gag cat gcg gtg ctt ggc ttg gaa gac gtg caa gac gct gcc gtt
32308Glu His Ala Val Leu Gly Leu Glu Asp Val Gln Asp Ala Ala Val
10590 10595 10600
atc gca ttt gac aat gtg gac agc gaa gag cca gaa atg gtt ggg
32353Ile Ala Phe Asp Asn Val Asp Ser Glu Glu Pro Glu Met Val Gly
10605 10610 10615
ttt gtc act att acc gaa gac aat cct gtc cgt gag gac gaa acc
32398Phe Val Thr Ile Thr Glu Asp Asn Pro Val Arg Glu Asp Glu Thr
10620 10625 10630
agc ggt caa gta gaa gac tgg gcg aac cac ttc gag ata agt acc
32443Ser Gly Gln Val Glu Asp Trp Ala Asn His Phe Glu Ile Ser Thr
10635 10640 10645
tac acc gat atc gcg gcg atc gat cag ggt agc att gga agt gac
32488Tyr Thr Asp Ile Ala Ala Ile Asp Gln Gly Ser Ile Gly Ser Asp
10650 10655 10660
ttt gta ggt tgg act tct atg tac gac gga agc gag atc gac aag
32533Phe Val Gly Trp Thr Ser Met Tyr Asp Gly Ser Glu Ile Asp Lys
10665 10670 10675
gca gag atg caa gaa tgg ctt gcc gat acc atg gcc tct atg ctc
32578Ala Glu Met Gln Glu Trp Leu Ala Asp Thr Met Ala Ser Met Leu
10680 10685 10690
gac ggg cag gcg ccg ggc aat gtg tta gag ata ggt aca ggc act
32623Asp Gly Gln Ala Pro Gly Asn Val Leu Glu Ile Gly Thr Gly Thr
10695 10700 10705
ggc atg gtc ctc ttc aat ctc ggc gac gga ctg cag agc tat gtc
32668Gly Met Val Leu Phe Asn Leu Gly Asp Gly Leu Gln Ser Tyr Val
10710 10715 10720
ggc ctc gaa cca tca aga tcg gcg gcc gct ttt gtc aac cag acg
32713Gly Leu Glu Pro Ser Arg Ser Ala Ala Ala Phe Val Asn Gln Thr
10725 10730 10735
att aag tcg ctc ccc acc ctt gct ggc aac gct gaa gta cac att
32758Ile Lys Ser Leu Pro Thr Leu Ala Gly Asn Ala Glu Val His Ile
10740 10745 10750
ggc act gcg acc gac gtg gcc cgt cta gat ggc ctc cgc ccc gac
32803Gly Thr Ala Thr Asp Val Ala Arg Leu Asp Gly Leu Arg Pro Asp
10755 10760 10765
tta gtg gta gtc aat tcg gta gtc cag tac ttc cca tca cca gag
32848Leu Val Val Val Asn Ser Val Val Gln Tyr Phe Pro Ser Pro Glu
10770 10775 10780
tac cta atg gaa gtc gtg gag gct ctt gca cgt ctg ccg ggc gtc
32893Tyr Leu Met Glu Val Val Glu Ala Leu Ala Arg Leu Pro Gly Val
10785 10790 10795
gag cga att ttc ttc gga gac gta cgt tcg tac gcc atc aac aga
32938Glu Arg Ile Phe Phe Gly Asp Val Arg Ser Tyr Ala Ile Asn Arg
10800 10805 10810
gat ttc ctg gct gcc aga gct cta cac gaa ctt ggc gac aga gcg
32983Asp Phe Leu Ala Ala Arg Ala Leu His Glu Leu Gly Asp Arg Ala
10815 10820 10825
act aag cac gag att cgg cga aag atg cta gag atg gaa gaa cgc
33028Thr Lys His Glu Ile Arg Arg Lys Met Leu Glu Met Glu Glu Arg
10830 10835 10840
gaa gag gag ctg ctc gtc gac cca gct ttc ttc acc atg ttg acc
33073Glu Glu Glu Leu Leu Val Asp Pro Ala Phe Phe Thr Met Leu Thr
10845 10850 10855
agc agt ctc cct ggc ctg att cag cat gtc gag atc ttg ccg aag
33118Ser Ser Leu Pro Gly Leu Ile Gln His Val Glu Ile Leu Pro Lys
10860 10865 10870
ctg atg aga gcc act aat gag ctc agc gcg tat cga tac act gct
33163Leu Met Arg Ala Thr Asn Glu Leu Ser Ala Tyr Arg Tyr Thr Ala
10875 10880 10885
gta gta cac gtg tgc cgt gcc ggt caa gag cct cgt tcc gtg cat
33208Val Val His Val Cys Arg Ala Gly Gln Glu Pro Arg Ser Val His
10890 10895 10900
acg atc gac gac gat gcc tgg gtg aat ctt gga gct tct cgg ttg
33253Thr Ile Asp Asp Asp Ala Trp Val Asn Leu Gly Ala Ser Arg Leu
10905 10910 10915
agt cgc cct acc ctt tca agc ctt ttg caa act tcc gag ggc gca
33298Ser Arg Pro Thr Leu Ser Ser Leu Leu Gln Thr Ser Glu Gly Ala
10920 10925 10930
tcg gcc gtc gca gta agc aat att cct tac agc aag acc atc aca
33343Ser Ala Val Ala Val Ser Asn Ile Pro Tyr Ser Lys Thr Ile Thr
10935 10940 10945
gag cga gcg ctc gtt agt gcg ctc gat gag gat gat atg caa gac
33388Glu Arg Ala Leu Val Ser Ala Leu Asp Glu Asp Asp Met Gln Asp
10950 10955 10960
tca tcg gac tgg ctg ctg gcc gtg cgc gag aca ggc aga tct tgt
33433Ser Ser Asp Trp Leu Leu Ala Val Arg Glu Thr Gly Arg Ser Cys
10965 10970 10975
tcc tcc ttc tcc gca aca gac ctt gtc gag ctt gct cga gag acg
33478Ser Ser Phe Ser Ala Thr Asp Leu Val Glu Leu Ala Arg Glu Thr
10980 10985 10990
ggc tgg cgt gtg gag ctc agc tgg gca cga cag tac tca cag aaa
33523Gly Trp Arg Val Glu Leu Ser Trp Ala Arg Gln Tyr Ser Gln Lys
10995 11000 11005
ggc gca ctc gat gct gtc ttc cac aga cac cct gtt tcc gct ggg
33568Gly Ala Leu Asp Ala Val Phe His Arg His Pro Val Ser Ala Gly
11010 11015 11020
agc ggg cgt gtc atg ttc cag ttt cca gtt gag acc gaa gat cga
33613Ser Gly Arg Val Met Phe Gln Phe Pro Val Glu Thr Glu Asp Arg
11025 11030 11035
ccg cac atc tca cgc acg aac cga cct tta cag cga ttg cag aag
33658Pro His Ile Ser Arg Thr Asn Arg Pro Leu Gln Arg Leu Gln Lys
11040 11045 11050
aag cga acc gag aca cat gtt cat gag cag ttg cgg gct ttg ctt
33703Lys Arg Thr Glu Thr His Val His Glu Gln Leu Arg Ala Leu Leu
11055 11060 11065
cca cga tac atg gtt cct acg cgg att gtg gcg ctt gat aag ctg
33748Pro Arg Tyr Met Val Pro Thr Arg Ile Val Ala Leu Asp Lys Leu
11070 11075 11080
ccc gtc aat gca aac ggc aag gtt gat cgt caa cag ctc gct agg
33793Pro Val Asn Ala Asn Gly Lys Val Asp Arg Gln Gln Leu Ala Arg
11085 11090 11095
aca gcc cag gtt ctc cca gcg agc aag gcg ccg tct gca tgc gtg
33838Thr Ala Gln Val Leu Pro Ala Ser Lys Ala Pro Ser Ala Cys Val
11100 11105 11110
gcc cca cgc aac gaa ttg gaa atg aca ctg tgt gaa gag ttc tcg
33883Ala Pro Arg Asn Glu Leu Glu Met Thr Leu Cys Glu Glu Phe Ser
11115 11120 11125
cag gtt ctt ggc gtc gag gtc ggc att act gac aat ttc ttc cac
33928Gln Val Leu Gly Val Glu Val Gly Ile Thr Asp Asn Phe Phe His
11130 11135 11140
ctg ggt ggc cac tct ctc atg gca aca aag ctt gcc gct cgt atc
33973Leu Gly Gly His Ser Leu Met Ala Thr Lys Leu Ala Ala Arg Ile
11145 11150 11155
agc cgt caa cta aat atc caa gtc tca gtc cga gac atc ttt gac
34018Ser Arg Gln Leu Asn Ile Gln Val Ser Val Arg Asp Ile Phe Asp
11160 11165 11170
tat ccc gtt ata gtc gac ctc aca gac aga ttg aga ctc cat cat
34063Tyr Pro Val Ile Val Asp Leu Thr Asp Arg Leu Arg Leu His His
11175 11180 11185
acg cgt atc ctt act cat gat cat gga caa cat gga cag cca gac
34108Thr Arg Ile Leu Thr His Asp His Gly Gln His Gly Gln Pro Asp
11190 11195 11200
ctc aag cca ttc acc ttg cta cca acc aac aat cct caa gaa ttc
34153Leu Lys Pro Phe Thr Leu Leu Pro Thr Asn Asn Pro Gln Glu Phe
11205 11210 11215
cta cag cat cac att ttg cca caa ctt gtt ccc gat cat gcg aag
34198Leu Gln His His Ile Leu Pro Gln Leu Val Pro Asp His Ala Lys
11220 11225 11230
atc ctc gat gtg tat ccc gtt aca aga ata cag aga agg ttt ctt
34243Ile Leu Asp Val Tyr Pro Val Thr Arg Ile Gln Arg Arg Phe Leu
11235 11240 11245
cat cat ccg aag cgc ggc ctc cct cgt ttt ccc tcc atg gtc ttc
34288His His Pro Lys Arg Gly Leu Pro Arg Phe Pro Ser Met Val Phe
11250 11255 11260
ttt gac ttc cct cct ggt tca gac cca cac aag cta aga tta gct
34333Phe Asp Phe Pro Pro Gly Ser Asp Pro His Lys Leu Arg Leu Ala
11265 11270 11275
tgt atg gca tta gtc cag cgt ttc gac att ctt cgc aca atc ttc
34378Cys Met Ala Leu Val Gln Arg Phe Asp Ile Leu Arg Thr Ile Phe
11280 11285 11290
ctt tct gtt tcg ggt caa ttc ttc caa gtg gtc ctg gat gga tat
34423Leu Ser Val Ser Gly Gln Phe Phe Gln Val Val Leu Asp Gly Tyr
11295 11300 11305
ggg att gtc ata ccg gtc atc gag gtt gac gaa gag cta gac gac
34468Gly Ile Val Ile Pro Val Ile Glu Val Asp Glu Glu Leu Asp Asp
11310 11315 11320
gcc acc cgt aaa tta cac gat tcc gat att cag cag ccc tta cgg
34513Ala Thr Arg Lys Leu His Asp Ser Asp Ile Gln Gln Pro Leu Arg
11325 11330 11335
ttg gga aaa ccg tta ata cgc att gct gtc ttg aaa agg cag cac
34558Leu Gly Lys Pro Leu Ile Arg Ile Ala Val Leu Lys Arg Gln His
11340 11345 11350
tcc aga gta cga gca gtc ttg cgc ttg tcg cat gct ctc tat gat
34603Ser Arg Val Arg Ala Val Leu Arg Leu Ser His Ala Leu Tyr Asp
11355 11360 11365
ggt ttg agc ttt gag cat atc atc caa tct ctt cat gcc ctt tat
34648Gly Leu Ser Phe Glu His Ile Ile Gln Ser Leu His Ala Leu Tyr
11370 11375 11380
ctc gat atc acc ctt tcg gcc cca ccg aag ttt gga ctc tac gta
34693Leu Asp Ile Thr Leu Ser Ala Pro Pro Lys Phe Gly Leu Tyr Val
11385 11390 11395
caa cat atg ata caa agt cgc gca gaa ggt tat gct ttc tgg cgg
34738Gln His Met Ile Gln Ser Arg Ala Glu Gly Tyr Ala Phe Trp Arg
11400 11405 11410
tct gtc ttg aag ggc tcg tcg atg aca att ctc gag cgt tct agc
34783Ser Val Leu Lys Gly Ser Ser Met Thr Ile Leu Glu Arg Ser Ser
11415 11420 11425
acc ctt caa tcg cgg cag ccg cat ctt gga cgt ttt ctc tct gcg
34828Thr Leu Gln Ser Arg Gln Pro His Leu Gly Arg Phe Leu Ser Ala
11430 11435 11440
gag aaa att att aag gct cct tta cac gcc aac aag tct gga atc
34873Glu Lys Ile Ile Lys Ala Pro Leu His Ala Asn Lys Ser Gly Ile
11445 11450 11455
aca cag gca aca gtg ttc gcg gcc gca aac gca ctc atg ctt gcg
34918Thr Gln Ala Thr Val Phe Ala Ala Ala Asn Ala Leu Met Leu Ala
11460 11465 11470
aat ctt act ggt act aat gac gtt gtg ttt gcc cgc att gtc tct
34963Asn Leu Thr Gly Thr Asn Asp Val Val Phe Ala Arg Ile Val Ser
11475 11480 11485
gga cgt caa tct ttg cct aag aac ttt cag cac gtt gtg gga cct
35008Gly Arg Gln Ser Leu Pro Lys Asn Phe Gln His Val Val Gly Pro
11490 11495 11500
tgc acg aac gat gtg ccc gtt cgc gta cgc atg gag cct ggc gtg
35053Cys Thr Asn Asp Val Pro Val Arg Val Arg Met Glu Pro Gly Val
11505 11510 11515
gga cca aaa gct tta ctc aga cag gtg caa gac cag tat gtt cat
35098Gly Pro Lys Ala Leu Leu Arg Gln Val Gln Asp Gln Tyr Val His
11520 11525 11530
agc ttc cct ttc gaa aca cta gga ttc gac gag atc aag gag aac
35143Ser Phe Pro Phe Glu Thr Leu Gly Phe Asp Glu Ile Lys Glu Asn
11535 11540 11545
tgt acg gac tgg cca gaa aga atc acg aat ttt ggg tgt tct aca
35188Cys Thr Asp Trp Pro Glu Arg Ile Thr Asn Phe Gly Cys Ser Thr
11550 11555 11560
act tac cag aac ttt gac att ttt ccc aaa agt cag att gac cac
35233Thr Tyr Gln Asn Phe Asp Ile Phe Pro Lys Ser Gln Ile Asp His
11565 11570 11575
cag cag att caa atg gct agc ttg gca agc gag tat cag aat cga
35278Gln Gln Ile Gln Met Ala Ser Leu Ala Ser Glu Tyr Gln Asn Arg
11580 11585 11590
gaa acc tgg gac gaa gcg ccg cta tac gac ctc aat gtc aca gga
35323Glu Thr Trp Asp Glu Ala Pro Leu Tyr Asp Leu Asn Val Thr Gly
11595 11600 11605
gta cct cag cct gac gga cgt cat atc aag ata tac gtg ggt gta
35368Val Pro Gln Pro Asp Gly Arg His Ile Lys Ile Tyr Val Gly Val
11610 11615 11620
gac ggg cag ctt tgc gat gaa agc acg ctt gat tgc att ctc tcg
35413Asp Gly Gln Leu Cys Asp Glu Ser Thr Leu Asp Cys Ile Leu Ser
11625 11630 11635
gat att tgt gag ggt gtg gtc tcg ctc aca gac gct ttg caa gaa
35458Asp Ile Cys Glu Gly Val Val Ser Leu Thr Asp Ala Leu Gln Glu
11640 11645 11650
ctt ccc gct gct agc att act gag tag aatcccaaga gagcaacacc
35505Leu Pro Ala Ala Ser Ile Thr Glu
11655
ctatcatgat agcgacagca cgttttcagt tcgtcagagc ttgactgaaa tgcttttcgt
35565ctactacatc tagcgtgtca taccagctag tagctacaac ggagcaacga ttggctgatg
35625agccaggacc tgaaaagaag aagaagatgg aaatatagcc ttggaatcta taataaag
35683611659PRTAureobasidium pullulans strain BP-1938 6Met Ser Arg Met Pro
Gln Gly Ala Ala Arg Arg Asn Asp Cys Val Ser 1 5
10 15 Glu His Gln Gly Thr Thr Asp Leu Glu Asp
Ile Val Arg Phe Trp Glu 20 25
30 Arg His Leu Asp Gly Val Asn Ala Ser Ala Phe Pro Ala Leu Ser
Ser 35 40 45 Ser
Leu Val Val Pro Lys Pro Lys Leu Gln Thr Glu His Arg Ile Ser 50
55 60 Leu Gly Thr Ala Val Ser
Asp Gln Trp Ser Asp Ala Val Ile Cys Arg 65 70
75 80 Ala Ala Leu Ala Val Ile Leu Ala Arg Tyr Thr
His Ala Thr Glu Ala 85 90
95 Leu Tyr Gly Ile Val Val Glu Gln Pro Ser Val Ser Asn Ala Gln Lys
100 105 110 Arg Ser
Ala Asp Asp Ala Ser Ser Ile Val Val Pro Ile Arg Val Gln 115
120 125 Cys Ala Ser Gly Gln Phe Gly
Asn Asp Ile Leu Ala Ala Ile Ala Thr 130 135
140 His Asp Ala Ser Cys Arg Ser Leu Ser Ala Ile Gly
Leu Asp Gly Ile 145 150 155
160 Arg Cys Leu Asp Asp Ala Lys Thr Val Ala Arg Gly Leu Gln Thr Val
165 170 175 Leu Thr Val
Thr Ser Arg Lys Ser Val Asp Ala Ser Ser Pro Asn Ile 180
185 190 Leu Asp Leu Glu Asn Ile Ala Ser
Ser His Gly Arg Ala Leu Met Ile 195 200
205 Glu Cys Gln Met Ser Thr Thr Ser Ala Cys Leu Arg Ala
Gln Tyr Asp 210 215 220
Ala Gly Ile Leu Arg Asn Glu Gln Val Val Arg Leu Leu Lys Gln Leu 225
230 235 240 Ala Leu Ser Ile
Gln His Phe Arg Gly Asn Ala Ala Asn Asp Leu Leu 245
250 255 Arg Asp Phe Cys Phe Ile Ser Pro Gly
Glu Glu Met Glu Ile Ala Tyr 260 265
270 Trp Asn Arg Arg Ser Ile Arg Thr Asn Glu Val Cys Ile His
Asp Val 275 280 285
Ile Phe Lys Arg Ala Thr Tyr Met Pro Thr Asp Thr Ala Val Ser Ala 290
295 300 Trp Asp Gly Glu Trp
Thr Tyr Ala Asp Leu Asp Val Val Ser Ser Cys 305 310
315 320 Leu Ala Asp Tyr Val Arg Ser Leu Asp Leu
Arg Ser Gly Gln Ala Ile 325 330
335 Pro Leu Cys Phe Glu Lys Ser Arg Asn Thr Ile Ala Ala Met Val
Ala 340 345 350 Val
Leu Lys Ala Gly His Pro Phe Cys Leu Ile Asp Pro Ser Thr Pro 355
360 365 Ser Ala Arg Ile Thr Gln
Met Cys Glu Gln Met Ser Ala Thr Val Ala 370 375
380 Phe Ala Ser Arg Ala Leu Cys Ser Ile Met Gln
Ala Gly Val Ser Arg 385 390 395
400 Cys Ile Ala Val Asp Asp Asp Leu Phe Gln Ser Leu Ser Ser Val Ile
405 410 415 Gly Cys
Pro Gln Met Ser Met Thr Arg Pro Gln Asp Leu Ala Tyr Val 420
425 430 Ile Phe Thr Ser Gly Ser Thr
Gly Ile Pro Lys Gly Ser Met Ile Glu 435 440
445 His Arg Gly Phe Ala Ser Cys Ala Leu Glu Phe Gly
Pro Gln Leu Leu 450 455 460
Ile Asp Arg Asn Thr Arg Ala Leu Gln Phe Ala Ser His Ala Phe Gly 465
470 475 480 Ala Cys Leu
Leu Glu Val Leu Val Thr Leu Met Leu Gly Gly Cys Val 485
490 495 Cys Val Pro Ser Glu Asn Asp Arg
Leu Asn Asn Leu Ser Gly Phe Ile 500 505
510 Glu Gln Ser Gly Val Asn Trp Thr Leu Phe Thr Pro Ser
Phe Ile Gly 515 520 525
Ala Leu Thr Pro Glu Thr Ile Arg Gly Val His Thr Val Val Leu Gly 530
535 540 Gly Glu Pro Met
Thr Pro Phe Ile Arg Asp Val Trp Ala Ser Lys Val 545 550
555 560 Gln Leu Leu Ser Ile Tyr Gly Gln Ser
Glu Ser Ser Thr Val Cys Ser 565 570
575 Val Val Lys Ile Lys Pro Asp Thr Thr Asp Leu Ser Ser Leu
Gly His 580 585 590
Ala Ile Gly Ala Arg Phe Trp Ile Val Asp Ala Glu Asn Pro Ser Arg
595 600 605 Leu Ala Pro Ile
Gly Cys Ile Gly Glu Leu Met Val Glu Ser Pro Gly 610
615 620 Ile Ala Arg Glu Tyr Leu Ser Ala
Gln Glu Ala Gln Met Ser Pro Phe 625 630
635 640 Ile Thr Lys Thr Pro Ala Trp Tyr Pro Met Lys Gln
Arg Cys Ser Pro 645 650
655 Val Lys Phe Tyr Met Thr Gly Asp Leu Ala Cys Tyr Gly Arg Asp Gly
660 665 670 Thr Val Met
Asn Leu Gly Arg Lys Asp Ser Gln Val Lys Ile Arg Gly 675
680 685 Gln Arg Val Glu Leu Gly Asp Val
Glu Thr Asn Leu Arg Ser Val Leu 690 695
700 Pro Lys His Ile Ile Pro Val Val Glu Ala Ile Asp Ser
Ile His Ala 705 710 715
720 Ser Gly Ser Lys Phe Leu Val Ala Ile Leu Ile Gly Ala Asn His Gly
725 730 735 Met Lys Asn Glu
Phe Asp Thr Glu Pro Arg Arg Glu Val Ser Ile Leu 740
745 750 Asp Glu Thr Ala Val Ile Arg Ile Arg
Lys Ser Met Gln Asp Leu Val 755 760
765 Pro Ser Tyr Cys Ile Pro Thr Gln Tyr Ile Cys Met Glu Arg
Leu Leu 770 775 780
Thr Thr Thr Thr Gly Lys Ala Asp Arg Lys Arg Leu Arg Ala Ile Cys 785
790 795 800 Val Asp Leu Leu Lys
Pro Ser Arg Arg Ala Met Val Pro Glu Ser Ser 805
810 815 Asp Gly Pro Thr Leu Lys Leu Thr Ala Gly
Gln Val Leu Asp Glu Ala 820 825
830 Trp His Arg Tyr Leu Arg Phe Asp Ser Val Leu Asp Gly Ser Lys
Ser 835 840 845 Lys
Phe Phe Asp Leu Asn Gly Asp Ser Ile Thr Ala Ile Lys Ile Ala 850
855 860 Asn Ala Ala Arg Lys His
Gly Val Met Leu Lys Val Ala Asp Ile Leu 865 870
875 880 Ala Asn Pro Thr Leu Ala Asp Leu Arg Ala Gln
Phe Gln Ile Asp Phe 885 890
895 Thr Pro Gln Asn Ser Ile Leu Arg Thr Ser Tyr Arg Gly Pro Ile Gln
900 905 910 Gln Ser
Phe Ala Gln Asn Arg Leu Trp Phe Leu Asp Gln Leu Asn Val 915
920 925 Gly Ala Ser Trp Tyr Ile Val
Pro Val Ala Val Arg Leu Gln Gly Thr 930 935
940 Val His Val Asp Ala Leu Val Thr Ala Leu Cys Ala
Leu Glu Gln Arg 945 950 955
960 His Glu Thr Leu Arg Thr Thr Phe Glu Glu Ser Asp Gly Glu Gly Ile
965 970 975 Gln Arg Ile
Gln Pro Ser Gly Leu Glu Gln Leu Arg Leu Ile Asp Val 980
985 990 Asp Cys Val Asp Ser Arg Asp Tyr
Gln Arg Val Leu Glu Glu Glu Gln 995 1000
1005 Thr Thr Pro Phe Glu Leu Ser Arg Glu Pro Gly
Trp Arg Val Ala 1010 1015 1020
Leu Leu Arg Leu Gly Asp Asp Asp His Val Leu Ser Ile Val Met
1025 1030 1035 His His Ile
Ile Ser Asp Gly Trp Ser Val Asp Val Leu Arg His 1040
1045 1050 Glu Leu Gly Gln Phe Tyr Ser Ala
Ala Leu Arg Gly Gln Asp Pro 1055 1060
1065 Leu Ser Gln Ile Ser Pro Leu Pro Ile Gln Tyr Arg Asp
Phe Ala 1070 1075 1080
Leu Trp Gln Arg Gln Asp Glu Gln Val Ala Glu His Gln Arg Gln 1085
1090 1095 Leu Glu His Trp Thr
Glu Gln Leu Ala Asp Ser Ser Pro Ala Glu 1100 1105
1110 Leu Leu Ser Asp His Pro Arg Pro Ser Ile
Leu Ser Gly Gln Ala 1115 1120 1125
Gly Ala Ile Pro Val Asn Val Gln Gly Ser Leu Tyr Gln Ala Leu
1130 1135 1140 Arg Ala
Phe Cys Arg Ala His Gln Val Thr Ser Phe Val Val Leu 1145
1150 1155 Leu Thr Ala Phe Arg Ile Ala
His Tyr Arg Leu Thr Gly Ala Glu 1160 1165
1170 Asp Ala Thr Ile Gly Thr Pro Ile Ala Asn Arg Asn
Arg Pro Glu 1175 1180 1185
Leu Glu Asn Met Ile Gly Phe Phe Val Asn Thr Gln Cys Met Arg 1190
1195 1200 Ile Val Ile Gly Ser
Asp Asp Thr Phe Glu Gly Leu Val Gln Gln 1205 1210
1215 Val Arg Ser Ile Thr Ala Ala Ala His Glu
Asn Gln Asp Val Pro 1220 1225 1230
Phe Glu Arg Ile Val Ser Ala Leu Leu Pro Gly Ser Arg Asp Thr
1235 1240 1245 Ser Arg
Asn Pro Leu Val Gln Leu Met Phe Ala Val His Ser Gln 1250
1255 1260 Arg Asn Leu Gly Gln Ile Ser
Leu Glu Gly Leu Gln Gly Glu Leu 1265 1270
1275 Leu Gly Val Ala Ser Pro Thr Arg Phe Asp Val Glu
Phe His Leu 1280 1285 1290
Phe Gln Glu Glu Asn Met Leu Ser Gly Arg Val Leu Phe Ser Asp 1295
1300 1305 Asp Leu Phe Glu Gln
Lys Thr Met Gln Gly Met Val Asp Val Phe 1310 1315
1320 Gln Glu Val Leu Ser Arg Gly Leu Glu Gln
Pro Gln Ile Pro Leu 1325 1330 1335
Ala Thr Leu Pro Leu Thr His Gly Leu Glu Glu Leu Arg Thr Met
1340 1345 1350 Gly Leu
Leu Asp Val Glu Lys Thr Asp Tyr Pro Arg Glu Ser Ser 1355
1360 1365 Val Val Asp Val Phe Arg Glu
Gln Ala Ala Ala Cys Ser Glu Ala 1370 1375
1380 Ile Ala Val Lys Asp Ser Ser Ala Gln Leu Thr Tyr
Ser Glu Leu 1385 1390 1395
Asp Arg Gln Ser Asp Glu Leu Ala Gly Trp Leu Arg Gln Gln Arg 1400
1405 1410 Leu Pro Ala Glu Ser
Leu Val Ala Val Leu Ala Pro Arg Ser Cys 1415 1420
1425 Gln Thr Ile Val Ala Phe Leu Gly Ile Leu
Lys Ala Asn Leu Ala 1430 1435 1440
Tyr Leu Pro Leu Asp Val Asn Val Pro Ala Thr Arg Leu Glu Ser
1445 1450 1455 Ile Leu
Ser Ala Val Gly Gly Arg Lys Leu Val Leu Leu Gly Ala 1460
1465 1470 Asp Val Ala Asp Pro Gly Leu
Arg Leu Ala Asp Val Glu Leu Val 1475 1480
1485 Arg Ile Gly Asp Thr Leu Gly Arg Cys Val Pro Gly
Ala Pro Gly 1490 1495 1500
Asp Asn Glu Ala Pro Val Val Gln Pro Ser Ala Thr Ser Leu Ala 1505
1510 1515 Tyr Val Ile Phe Thr
Ser Gly Ser Thr Gly Lys Pro Lys Gly Val 1520 1525
1530 Met Val Glu His Arg Gly Val Val Arg Leu
Val Lys Gln Ser Asn 1535 1540 1545
Val Val Tyr His Leu Pro Ser Thr Ser Arg Val Ala His Leu Ser
1550 1555 1560 Asn Leu
Ala Phe Asp Ala Ser Ala Trp Glu Ile Tyr Ala Ala Leu 1565
1570 1575 Leu Asn Gly Gly Thr Leu Ile
Cys Ile Asp Tyr Phe Thr Thr Leu 1580 1585
1590 Asp Cys Ser Ala Leu Gly Ala Lys Phe Ile Lys Glu
Lys Ile Val 1595 1600 1605
Ala Thr Met Ile Pro Pro Ala Leu Leu Lys Gln Cys Leu Ala Ile 1610
1615 1620 Phe Pro Thr Ala Leu
Ser Glu Leu Val Leu Leu Phe Ala Ala Gly 1625 1630
1635 Asp Arg Phe Ser Ser Gly Asp Ala Val Glu
Val Gln Arg His Thr 1640 1645 1650
Lys Gly Ala Val Cys Asn Ala Tyr Gly Pro Thr Glu Asn Thr Ile
1655 1660 1665 Leu Ser
Thr Ile Tyr Glu Val Lys Gln Asn Glu Asn Phe Pro Asn 1670
1675 1680 Gly Val Pro Ile Gly Arg Ala
Val Ser Asn Ser Gly Ala Tyr Val 1685 1690
1695 Met Asp Pro Gln Gln Gln Leu Val Pro Leu Gly Val
Met Gly Glu 1700 1705 1710
Leu Val Val Thr Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro 1715
1720 1725 Ser Leu Asp Ala Asp
Arg Phe Val Gln Val Ser Val Asn Gly Gln 1730 1735
1740 Leu Val Arg Ala Tyr Arg Thr Gly Asp Arg
Val Arg Cys Arg Pro 1745 1750 1755
Cys Asp Gly Gln Ile Glu Phe Phe Gly Arg Met Asp Arg Gln Val
1760 1765 1770 Lys Ile
Arg Gly His Arg Ile Glu Leu Ala Glu Val Glu His Ala 1775
1780 1785 Val Leu Gly Leu Glu Asp Val
Gln Asp Ala Ala Val Ile Ala Phe 1790 1795
1800 Asp Asn Val Asp Ser Glu Glu Pro Glu Met Val Gly
Phe Val Thr 1805 1810 1815
Ile Thr Glu Asp Asn Pro Val Arg Glu Asp Glu Thr Ser Gly Gln 1820
1825 1830 Val Glu Asp Trp Ala
Asn His Phe Glu Ile Ser Thr Tyr Thr Asp 1835 1840
1845 Ile Ala Ala Ile Asp Gln Gly Ser Ile Gly
Ser Asp Phe Val Gly 1850 1855 1860
Trp Thr Ser Met Tyr Asp Gly Ser Glu Ile Asp Lys Ala Glu Met
1865 1870 1875 Gln Glu
Trp Leu Ala Asp Thr Met Ala Ser Met Leu Asp Gly Gln 1880
1885 1890 Ala Pro Gly Asn Val Leu Glu
Ile Gly Thr Gly Thr Gly Met Val 1895 1900
1905 Leu Phe Asn Leu Gly Asp Gly Leu Gln Ser Tyr Val
Gly Leu Glu 1910 1915 1920
Pro Ser Arg Ser Ala Ala Ala Phe Val Asn Gln Thr Ile Lys Ser 1925
1930 1935 Leu Pro Thr Leu Ala
Gly Asn Ala Glu Val His Ile Gly Thr Ala 1940 1945
1950 Thr Asp Val Ala Arg Leu Asp Gly Leu Arg
Pro Asp Leu Val Val 1955 1960 1965
Val Asn Ser Val Val Gln Tyr Phe Pro Ser Pro Glu Tyr Leu Met
1970 1975 1980 Glu Val
Val Glu Ala Leu Ala Arg Leu Pro Gly Val Glu Arg Ile 1985
1990 1995 Phe Phe Gly Asp Val Arg Ser
Tyr Ala Ile Asn Arg Asp Phe Leu 2000 2005
2010 Ala Ala Arg Ala Leu His Glu Leu Gly Asp Arg Ala
Thr Lys His 2015 2020 2025
Glu Ile Arg Arg Lys Met Leu Glu Met Glu Glu Arg Glu Glu Glu 2030
2035 2040 Leu Leu Val Asp Pro
Ala Phe Phe Thr Met Leu Thr Ser Ser Leu 2045 2050
2055 Pro Gly Leu Ile Gln His Val Glu Ile Leu
Pro Lys Leu Met Arg 2060 2065 2070
Ala Thr Asn Glu Leu Ser Ala Tyr Arg Tyr Thr Ala Val Val His
2075 2080 2085 Val Cys
Arg Ala Gly Gln Glu Pro Arg Ser Val His Thr Ile Asp 2090
2095 2100 Asp Asp Ala Trp Val Asn Leu
Gly Ala Ser Arg Leu Ser Arg Pro 2105 2110
2115 Thr Leu Ser Ser Leu Leu Gln Thr Ser Glu Gly Ala
Ser Ala Val 2120 2125 2130
Ala Val Ser Asn Ile Pro Tyr Ser Lys Thr Ile Thr Glu Arg Ala 2135
2140 2145 Leu Val Ser Ala Leu
Asp Glu Asp Asp Met Gln Asp Ser Ser Asp 2150 2155
2160 Trp Leu Leu Ala Val Arg Glu Thr Gly Arg
Ser Cys Ser Ser Phe 2165 2170 2175
Ser Ala Thr Asp Leu Val Glu Leu Ala Arg Glu Thr Gly Trp Arg
2180 2185 2190 Val Glu
Leu Ser Trp Ala Arg Gln Tyr Ser Gln Lys Gly Ala Leu 2195
2200 2205 Asp Ala Val Phe His Arg His
Pro Val Ser Ala Gly Ser Gly Arg 2210 2215
2220 Val Met Phe Gln Phe Pro Val Glu Thr Glu Asp Arg
Pro His Ile 2225 2230 2235
Ser Arg Thr Asn Arg Pro Leu Gln Arg Leu Gln Lys Lys Arg Thr 2240
2245 2250 Glu Thr His Val His
Glu Gln Leu Arg Ala Leu Leu Pro Arg Tyr 2255 2260
2265 Met Val Pro Thr Arg Ile Val Ala Leu Asp
Lys Leu Pro Val Asn 2270 2275 2280
Ala Asn Gly Lys Val Asp Arg Gln Gln Leu Ala Arg Thr Ala Gln
2285 2290 2295 Val Leu
Pro Ala Ser Lys Ala Pro Ser Ala Cys Val Ala Pro Arg 2300
2305 2310 Asn Glu Leu Glu Met Thr Leu
Cys Glu Glu Phe Ser Gln Val Leu 2315 2320
2325 Gly Val Glu Val Gly Ile Thr Asp Asn Phe Phe His
Leu Gly Gly 2330 2335 2340
His Ser Leu Met Ala Thr Lys Phe Ala Ala Arg Ile Ser Arg Arg 2345
2350 2355 Leu Asn Ala Ile Val
Ser Val Lys Asn Val Phe Asp His Pro Val 2360 2365
2370 Pro Met Asp Leu Ala Ala Thr Ile Gln Glu
Gly Ser Lys Leu His 2375 2380 2385
Thr Pro Ile Pro Arg Thr Ala Tyr Ser Gly Pro Val Glu Gln Ser
2390 2395 2400 Phe Ala
Gln Gly Arg Leu Trp Phe Leu Asp Gln Phe Asn Pro Ser 2405
2410 2415 Ser Ile Gly Tyr Val Met Pro
Phe Ala Ala Arg Leu His Gly Gln 2420 2425
2430 Leu Gln Ile Glu Ala Leu Thr Ala Ala Leu Phe Ala
Leu Glu Gln 2435 2440 2445
Arg His Glu Ile Leu Arg Thr Thr Leu Asp Ala His Asp Gly Val 2450
2455 2460 Gly Met Gln Ile Val
His Ala Glu His Pro Gln Gln Leu Arg Ile 2465 2470
2475 Ile Asp Val Ser Ala Lys Ala Ser Ser Ser
Tyr Ala Gln Thr Leu 2480 2485 2490
Arg Asp Glu Gln Ala Ser Pro Phe Asp Leu Ser Lys Glu Pro Gly
2495 2500 2505 Trp Arg
Val Ser Leu Leu Gln Leu Ser Glu Ile Asp Tyr Val Leu 2510
2515 2520 Ser Ile Val Met His His Thr
Ile Tyr Asp Gly Trp Ser Leu Asp 2525 2530
2535 Val Leu Arg Arg Glu Leu Ser Gln Phe Tyr Ala Ala
Ala Ile Arg 2540 2545 2550
Gly Arg Glu Pro Leu Ser Thr Ile Glu Pro Leu Pro Ile Gln Tyr 2555
2560 2565 Arg Asp Phe Ser Val
Trp Gln Lys Gln Glu Asp Gln Val Ala Glu 2570 2575
2580 His Arg Arg Gln Leu His Tyr Trp Ile Glu
Gln Leu Asp Gly Ser 2585 2590 2595
Ser Pro Ala Glu Phe Leu Asn Asp Lys Pro Arg Pro Thr Leu Leu
2600 2605 2610 Ser Gly
Lys Ala Gly Val Val Glu Ile Ala Val Lys Gly Thr Val 2615
2620 2625 Tyr Gln Arg Leu Leu Glu Phe
Cys Arg Leu His Gln Val Thr Ser 2630 2635
2640 Phe Met Val Leu Leu Ala Ala Phe Arg Ala Thr His
Tyr Arg Leu 2645 2650 2655
Thr Gly Thr Glu Asp Ala Thr Val Gly Thr Pro Ile Ala Asn Arg 2660
2665 2670 Asn Arg Pro Glu Leu
Glu Asn Met Ile Gly Leu Phe Val Asn Thr 2675 2680
2685 Gln Cys Ile Arg Leu Lys Ile Glu Asp Asn
Asp Thr Leu Glu Glu 2690 2695 2700
Leu Val Gln His Val Arg Ala Thr Ile Thr Ala Ser Ile Ser Asn
2705 2710 2715 Gln Asp
Val Pro Phe Glu Gln Val Val Ser Ala Leu Leu Pro Gly 2720
2725 2730 Ser Arg Asp Thr Ser Arg Asn
Pro Leu Val Gln Leu Thr Phe Ala 2735 2740
2745 Val His Ser Gln Arg Asn Leu Ala Asp Ile Gln Leu
Glu Asn Val 2750 2755 2760
Glu Thr Asn Ala Met Pro Ile Cys Pro Ser Thr Arg Phe Asp Ala 2765
2770 2775 Glu Phe His Leu Phe
Gln Glu Glu Asn Met Leu Ser Gly Arg Val 2780 2785
2790 Leu Phe Ser Asp Asp Leu Phe Glu Gln Lys
Thr Met Gln Gly Met 2795 2800 2805
Val Asp Val Phe Gln Glu Val Leu Ser Arg Gly Leu Glu Gln Pro
2810 2815 2820 Gln Ile
Pro Leu Ala Thr Leu Pro Leu Thr His Gly Leu Glu Glu 2825
2830 2835 Leu Arg Thr Met Gly Leu Leu
Asp Val Glu Lys Thr Asp Tyr Pro 2840 2845
2850 Arg Glu Ser Ser Val Val Asp Val Phe Arg Glu Gln
Ala Ala Ala 2855 2860 2865
Cys Ser Glu Ala Ile Ala Val Lys Asp Ser Ser Ala Gln Leu Thr 2870
2875 2880 Tyr Ser Glu Leu Asp
Arg Gln Ser Asp Glu Leu Ala Gly Trp Leu 2885 2890
2895 Arg Gln Gln Arg Leu Pro Ala Glu Ser Leu
Val Ala Val Leu Ala 2900 2905 2910
Pro Arg Ser Cys Gln Thr Ile Val Ala Phe Leu Gly Ile Leu Lys
2915 2920 2925 Ala Asn
Leu Ala Tyr Leu Pro Leu Asp Val Asn Val Pro Ala Thr 2930
2935 2940 Arg Leu Glu Ser Ile Leu Ser
Ala Val Gly Gly Arg Lys Leu Val 2945 2950
2955 Leu Leu Gly Ala Asp Val Ala Asp Pro Gly Leu Arg
Leu Ala Asp 2960 2965 2970
Val Glu Leu Val Arg Ile Gly Asp Thr Leu Gly Arg Cys Val Pro 2975
2980 2985 Gly Ala Pro Gly Asp
Asn Glu Ala Pro Val Val Gln Pro Ser Ala 2990 2995
3000 Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser
Gly Ser Thr Gly Lys 3005 3010 3015
Pro Lys Gly Val Met Val Glu His Arg Ser Ile Val Arg Leu Met
3020 3025 3030 Arg His
Ser Asn Val Ser Ser Arg Leu Leu Leu His Pro Arg Met 3035
3040 3045 Thr His Leu Ser Asn Leu Ala
Phe Asp Ala Ser Val Trp Glu Ile 3050 3055
3060 Phe Leu Thr Leu Leu Asn Gly Gly Thr Leu Ile Cys
Ile Asp Tyr 3065 3070 3075
Leu Ser Ser Leu Asp Cys Arg Ala Leu Gly Val Ser Ile Leu Glu 3080
3085 3090 His Gln Val Asp Ala
Ser Val Leu Pro Pro Ala Leu Leu Lys Gln 3095 3100
3105 Cys Leu Ala Asn Val Pro Glu Ala Leu Ala
Ser Leu Gln Val Leu 3110 3115 3120
Leu Ser Ala Gly Asp Arg Leu Asp Ser Arg Asp Ala Ile Glu Ser
3125 3130 3135 Cys Ala
Leu Val Arg Gly Ser Val Tyr Asn Gly Tyr Gly Pro Thr 3140
3145 3150 Glu Asn Gly Ile Gln Ser Thr
Ile Tyr Glu Val Lys Ala Asp Ala 3155 3160
3165 Glu Phe Val Asn Gly Val Pro Ile Gly Arg Ala Val
Ser Asn Ser 3170 3175 3180
Gly Ala Tyr Val Met Asp Pro Gln Gln Gln Leu Val Pro Leu Gly 3185
3190 3195 Val Met Gly Glu Leu
Val Val Thr Gly Asp Gly Leu Ala Arg Gly 3200 3205
3210 Tyr Thr Asp Pro Ser Leu Asp Ala Asp Arg
Phe Val Gln Val Ser 3215 3220 3225
Val Asn Gly Gln Leu Val Arg Ala Tyr Arg Thr Gly Asp Arg Val
3230 3235 3240 Arg Cys
Arg Pro Cys Asp Gly Gln Ile Glu Phe Phe Gly Arg Met 3245
3250 3255 Asp Arg Gln Val Lys Ile Arg
Gly His Arg Ile Glu Leu Ala Glu 3260 3265
3270 Val Glu His Ala Val Leu Gly Leu Glu Asp Val Gln
Asp Ala Ala 3275 3280 3285
Val Leu Ile Ala Gln Thr Ala Glu Asn Glu Glu Leu Val Gly Phe 3290
3295 3300 Phe Thr Leu Arg Gln
Thr Gln Ala Val Gln Ser Asn Gly Ala Ala 3305 3310
3315 Gly Val Val Pro Glu His Ser Asp Ser Glu
Leu Ala Gln Ser Cys 3320 3325 3330
Ser Cys Thr Gln Thr Glu Arg Arg Val Arg Asn Arg Leu Gln Ser
3335 3340 3345 Cys Leu
Pro Arg Tyr Met Val Pro Ser Arg Met Val Leu Leu Asp 3350
3355 3360 Arg Leu Pro Val Asn Pro Asn
Gly Lys Val Asp Arg Gln Glu Leu 3365 3370
3375 Thr Arg Arg Ala Gln Asp Leu Pro Ile Ser Glu Ser
Ser Pro Val 3380 3385 3390
His Val Lys Pro Arg Thr Glu Leu Glu Arg Ser Leu Cys Glu Glu 3395
3400 3405 Phe Ala Asp Val Ile
Gly Leu Glu Val Gly Val Thr Asp Asn Phe 3410 3415
3420 Phe Asp Leu Gly Gly His Ser Leu Met Ala
Met Lys Leu Ala Ala 3425 3430 3435
Arg Ile Ser Arg Arg Ser Asn Ala His Ile Ser Val Lys Asp Ile
3440 3445 3450 Phe Asp
His Pro Leu Ile Ala Asp Leu Ala Met Lys Ile Arg Glu 3455
3460 3465 Gly Ser Asp Leu His Thr Pro
Ile Pro His Arg Met Tyr Val Gly 3470 3475
3480 Pro Ile Gln Leu Ser Phe Ala Gln Gly Arg Leu Trp
Phe Leu Asp 3485 3490 3495
Gln Leu Asn Leu Gly Ala Ser Trp Tyr Val Met Pro Leu Ala Met 3500
3505 3510 Arg Leu Gln Gly Ser
Leu Gln Leu Asp Ala Leu Glu Thr Ala Leu 3515 3520
3525 Phe Ala Ile Glu Gln Arg His Glu Thr Leu
Arg Met Thr Phe Ala 3530 3535 3540
Glu Gln Asp Gly Val Ala Val Gln Val Val His Ala Ala His Tyr
3545 3550 3555 Lys His
Ile Lys Met Ile Asp Lys Pro Leu Arg Gln Lys Ile Asp 3560
3565 3570 Val Leu Lys Met Leu Glu Glu
Glu Arg Thr Thr Pro Phe Glu Leu 3575 3580
3585 Ser Arg Glu Pro Gly Trp Arg Val Ala Leu Leu Arg
Leu Gly Asp 3590 3595 3600
Asp Asp His Val Leu Ser Ile Val Met His His Ile Ile Ser Asp 3605
3610 3615 Gly Trp Ser Val Asp
Val Leu Arg His Glu Leu Gly Gln Phe Tyr 3620 3625
3630 Ser Ala Ala Leu Arg Gly Gln Asp Pro Leu
Ser Gln Ile Ser Pro 3635 3640 3645
Leu Pro Ile Gln Tyr Arg Asp Phe Ala Leu Trp Gln Arg Gln Asp
3650 3655 3660 Glu Gln
Val Ala Glu His Gln Arg Gln Leu Glu His Trp Thr Glu 3665
3670 3675 Gln Leu Ala Asp Ser Ser Pro
Ala Glu Leu Leu Ser Asp His Pro 3680 3685
3690 Arg Pro Ser Ile Leu Ser Gly Gln Ala Gly Ala Ile
Pro Val Asn 3695 3700 3705
Val Gln Gly Ser Leu Tyr Gln Ala Leu Arg Ala Phe Cys Arg Ala 3710
3715 3720 His Gln Val Thr Ser
Phe Val Val Leu Leu Thr Ala Phe Arg Ile 3725 3730
3735 Ala His Tyr Arg Leu Thr Gly Ala Glu Asp
Ala Thr Ile Gly Thr 3740 3745 3750
Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly
3755 3760 3765 Phe Phe
Val Asn Thr Gln Cys Met Arg Ile Val Ile Gly Ser Asp 3770
3775 3780 Asp Thr Phe Glu Gly Leu Val
Gln Gln Val Arg Ser Ile Thr Ala 3785 3790
3795 Ala Ala His Glu Asn Gln Asp Val Pro Phe Glu Arg
Ile Val Ser 3800 3805 3810
Ala Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val 3815
3820 3825 Gln Leu Met Phe Ala
Val His Ser Gln Arg Asn Leu Gly Gln Ile 3830 3835
3840 Ser Leu Glu Gly Leu Gln Gly Glu Leu Leu
Gly Val Ala Ala Thr 3845 3850 3855
Thr Arg Phe Asp Val Glu Phe His Leu Phe Gln Asp Asp Asp Lys
3860 3865 3870 Leu Ser
Gly Asn Val Leu Phe Ala Thr Glu Leu Phe Glu Gln Lys 3875
3880 3885 Thr Met Gln Gly Met Val Asp
Val Phe Gln Glu Val Leu Ser Arg 3890 3895
3900 Gly Leu Glu Gln Pro Gln Ile Pro Leu Ala Thr Leu
Pro Leu Thr 3905 3910 3915
His Gly Leu Glu Glu Leu Arg Thr Met Gly Leu Leu Asp Val Glu 3920
3925 3930 Lys Thr Asp Tyr Pro
Arg Glu Ser Ser Val Val Asp Val Phe Arg 3935 3940
3945 Glu Gln Ala Ala Ala Cys Ser Glu Ala Ile
Ala Val Lys Asp Ser 3950 3955 3960
Ser Ala Gln Leu Thr Tyr Ser Glu Leu Asp Arg Gln Ser Asp Glu
3965 3970 3975 Leu Ala
Gly Trp Leu Arg Gln Gln Arg Leu Pro Ala Glu Ser Leu 3980
3985 3990 Val Ala Val Leu Ala Pro Arg
Ser Cys Gln Thr Ile Val Ala Phe 3995 4000
4005 Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro
Leu Asp Val 4010 4015 4020
Asn Val Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser Ala Val Gly 4025
4030 4035 Gly Arg Lys Leu Val
Leu Leu Gly Ala Asp Val Ala Asp Pro Gly 4040 4045
4050 Leu Arg Leu Ala Asp Val Glu Leu Val Arg
Ile Gly Asp Thr Leu 4055 4060 4065
Gly Arg Cys Val Pro Gly Ala Pro Gly Asp Asn Glu Ala Pro Val
4070 4075 4080 Val Gln
Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe Thr Ser 4085
4090 4095 Gly Ser Thr Gly Lys Pro Lys
Gly Val Met Val Glu His Arg Ser 4100 4105
4110 Ile Val Arg Leu Met Arg His Ser Asn Val Ser Ser
Arg Leu Leu 4115 4120 4125
Leu His Pro Arg Met Thr His Leu Ser Asn Leu Ala Phe Asp Ala 4130
4135 4140 Ser Val Trp Glu Ile
Phe Leu Thr Leu Leu Asn Gly Gly Thr Leu 4145 4150
4155 Ile Cys Ile Asp Tyr Leu Ser Ser Leu Asp
Cys Arg Ala Leu Gly 4160 4165 4170
Val Ser Ile Leu Glu His Gln Val Asp Ala Ser Val Leu Pro Pro
4175 4180 4185 Ala Leu
Leu Lys Gln Cys Leu Ala Asn Val Pro Glu Ala Leu Ala 4190
4195 4200 Ser Leu Gln Val Leu Leu Ser
Ala Gly Asp Arg Leu Asp Ser Arg 4205 4210
4215 Asp Ala Ile Glu Ser Cys Ala Leu Val Arg Gly Ser
Val Tyr Asn 4220 4225 4230
Gly Tyr Gly Pro Thr Glu Asn Gly Ile Gln Ser Thr Ile Tyr Glu 4235
4240 4245 Val Lys Ala Asp Ala
Glu Phe Val Asn Gly Val Pro Ile Gly Arg 4250 4255
4260 Ala Val Ser Asn Ser Gly Ala Tyr Val Met
Asp Pro Gln Gln Gln 4265 4270 4275
Leu Val Pro Leu Gly Val Met Gly Glu Leu Val Val Thr Gly Asp
4280 4285 4290 Gly Leu
Ala Arg Gly Tyr Thr Asp Pro Ser Leu Asp Ala Asp Arg 4295
4300 4305 Phe Val Gln Val Ser Val Asn
Gly Gln Leu Val Arg Ala Tyr Arg 4310 4315
4320 Thr Gly Asp Arg Val Arg Cys Arg Pro Cys Asp Gly
Gln Ile Glu 4325 4330 4335
Phe Phe Gly Arg Met Asp Arg Gln Val Lys Ile Arg Gly His Arg 4340
4345 4350 Ile Glu Leu Ala Glu
Val Glu His Ala Val Leu Gly Leu Glu Asp 4355 4360
4365 Val Gln Asp Ala Ala Val Ile Ala Phe Asp
Asn Val Asp Ser Glu 4370 4375 4380
Glu Pro Glu Met Val Gly Phe Val Thr Ile Thr Glu Asp Asn Pro
4385 4390 4395 Val Arg
Glu Asp Glu Thr Ser Gly Gln Val Glu Asp Trp Ala Asn 4400
4405 4410 His Phe Glu Ile Ser Thr Tyr
Thr Asp Ile Ala Ala Ile Asp Gln 4415 4420
4425 Gly Ser Ile Gly Ser Asp Phe Val Gly Trp Thr Ser
Met Tyr Asp 4430 4435 4440
Gly Ser Glu Ile Asp Lys Ala Glu Met Gln Glu Trp Leu Ala Asp 4445
4450 4455 Thr Met Ala Ser Met
Leu Asp Gly Gln Ala Pro Gly Asn Val Leu 4460 4465
4470 Glu Ile Gly Thr Gly Thr Gly Met Val Leu
Phe Asn Leu Gly Asp 4475 4480 4485
Gly Leu Gln Ser Tyr Val Gly Leu Glu Pro Ser Arg Ser Ala Ala
4490 4495 4500 Ala Phe
Val Asn Gln Thr Ile Lys Ser Leu Pro Thr Leu Ala Gly 4505
4510 4515 Asn Ala Glu Val His Ile Gly
Thr Ala Thr Asp Val Ala Arg Leu 4520 4525
4530 Asp Gly Leu Arg Pro Asp Leu Val Val Val Asn Ser
Val Val Gln 4535 4540 4545
Tyr Phe Pro Ser Pro Glu Tyr Leu Met Glu Val Val Glu Ala Leu 4550
4555 4560 Ala Arg Leu Pro Gly
Val Glu Arg Ile Phe Phe Gly Asp Val Arg 4565 4570
4575 Ser Tyr Ala Ile Asn Arg Asp Phe Leu Ala
Ala Arg Ala Leu His 4580 4585 4590
Glu Leu Gly Asp Arg Ala Thr Lys His Glu Ile Arg Arg Lys Met
4595 4600 4605 Leu Glu
Met Glu Glu Arg Glu Glu Glu Leu Leu Val Asp Pro Ala 4610
4615 4620 Phe Phe Thr Met Leu Thr Ser
Ser Leu Pro Gly Leu Ile Gln His 4625 4630
4635 Val Glu Ile Leu Pro Lys Leu Met Arg Ala Thr Asn
Glu Leu Ser 4640 4645 4650
Ala Tyr Arg Tyr Thr Ala Val Val His Val Cys Arg Ala Gly Gln 4655
4660 4665 Glu Pro Arg Ser Val
His Thr Ile Asp Asp Asp Ala Trp Val Asn 4670 4675
4680 Leu Gly Ala Ser Arg Leu Ser Arg Pro Thr
Leu Ser Ser Leu Leu 4685 4690 4695
Gln Thr Ser Glu Gly Ala Ser Ala Val Ala Val Ser Asn Ile Pro
4700 4705 4710 Tyr Ser
Lys Thr Ile Thr Glu Arg Ala Leu Val Ser Ala Leu Asp 4715
4720 4725 Glu Asp Asp Met Gln Asp Ser
Ser Asp Trp Leu Leu Ala Val Arg 4730 4735
4740 Glu Thr Gly Arg Ser Cys Ser Ser Phe Ser Ala Thr
Asp Leu Val 4745 4750 4755
Glu Leu Ala Arg Glu Thr Gly Trp Arg Val Glu Leu Ser Trp Ala 4760
4765 4770 Arg Gln Tyr Ser Gln
Lys Gly Ala Leu Asp Ala Val Phe His Arg 4775 4780
4785 His Pro Val Ser Ala Gly Ser Gly Arg Val
Met Phe Gln Phe Pro 4790 4795 4800
Val Glu Thr Glu Asp Arg Pro His Ile Ser Arg Thr Asn Arg Pro
4805 4810 4815 Leu Gln
Arg Leu Gln Lys Lys Arg Thr Glu Thr His Val His Glu 4820
4825 4830 Gln Leu Arg Ala Leu Leu Pro
Arg Tyr Met Val Pro Thr Arg Ile 4835 4840
4845 Val Ala Leu Asp Lys Leu Pro Val Asn Ala Asn Gly
Lys Val Asp 4850 4855 4860
Arg Gln Gln Leu Ala Arg Thr Ala Gln Val Leu Pro Ala Ser Lys 4865
4870 4875 Ala Pro Ser Ala Cys
Val Ala Pro Arg Asn Glu Leu Glu Met Thr 4880 4885
4890 Leu Cys Glu Glu Phe Ser Gln Val Leu Gly
Val Glu Val Gly Ile 4895 4900 4905
Thr Asp Asn Phe Phe His Leu Gly Gly His Ser Leu Met Ala Thr
4910 4915 4920 Lys Leu
Ala Ala Arg Ile Ser His Arg Leu His Thr Arg Ile Ser 4925
4930 4935 Val Lys His Ile Phe Asp His
Pro Leu Ile Gly Asp Leu Ser Val 4940 4945
4950 His Ile Ala Asp Ser Pro Val Pro Leu Leu Thr Ile
Thr Arg Ala 4955 4960 4965
Gln His Ala Gly Ala Val Glu Gln Ser Phe Ala Gln Ala Arg Leu 4970
4975 4980 Trp Phe Leu Val Gln
Leu Gly Leu Glu Ser Pro Ser Tyr Ile Ile 4985 4990
4995 Pro Ile Val Leu Arg Leu His Gly Ser Leu
Ser Lys Thr Ala Ile 5000 5005 5010
Glu Gly Ala Leu Ser Ala Leu Met Glu Arg His Glu Val Leu Arg
5015 5020 5025 Thr Thr
Phe Glu Asp His Lys Gly Ile Gly Met Gln Val Val Gln 5030
5035 5040 Asp His Arg His Gln Asp Leu
Val Val Ile Asp Val Ala Gly Gln 5045 5050
5055 Gly Ser Leu Asp Tyr Lys Gln His Leu Tyr Met Glu
His Val Lys 5060 5065 5070
Pro Phe Asp Leu Thr Arg Asp Pro Gly Trp Arg Val Ala Leu Leu 5075
5080 5085 Arg Leu Gly Asp Asp
Asp His Val Leu Ser Ile Val Met His His 5090 5095
5100 Ile Ile Ser Asp Gly Trp Ser Ile Asp Ile
Leu Leu Arg Glu Leu 5105 5110 5115
Gly Gln Phe Tyr Ser Ala Ala Leu Arg Gly Gln Asp Pro Leu Ser
5120 5125 5130 Gln Thr
Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ala Leu Trp 5135
5140 5145 Gln Lys Gln Asp His Gln Leu
Ala Asp His Glu Lys Gln Leu Arg 5150 5155
5160 Tyr Trp Glu Glu Gln Leu Ala Glu Ser Ser Pro Ala
Glu Leu Leu 5165 5170 5175
Cys Asp His Ala Arg Pro Thr Thr Pro Ser Gly Gln Ala Gly Ser 5180
5185 5190 Ile Pro Val Asn Val
Gln Gly Ser Leu Tyr Gln Ala Leu Arg Ala 5195 5200
5205 Phe Cys Arg Ala His Gln Val Thr Ser Phe
Val Val Leu Leu Thr 5210 5215 5220
Ala Phe Arg Ile Ala His Tyr Arg Leu Thr Gly Ala Glu Asp Ala
5225 5230 5235 Thr Ile
Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro Glu Leu Glu 5240
5245 5250 Asn Met Ile Gly Phe Phe Val
Asn Thr Gln Cys Met Arg Ile Val 5255 5260
5265 Ile Gly Ser Asp Asp Thr Phe Glu Gly Leu Val Gln
Gln Val Arg 5270 5275 5280
Ser Ile Thr Ala Ala Ala His Glu Asn Gln Asp Val Pro Phe Glu 5285
5290 5295 Arg Ile Val Ser Ala
Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg 5300 5305
5310 Asn Pro Leu Val Gln Leu Leu Phe Ala Val
His Ala Tyr Gln Glu 5315 5320 5325
Val Glu Asn Phe Ala Ile Pro Gly Val His Ser Glu Leu Val Gln
5330 5335 5340 Gly Thr
Thr Phe Thr Arg Phe Asp Val Glu Phe His Leu Leu Glu 5345
5350 5355 Asp Pro Asp Lys Leu Ser Gly
Asn Val Leu Phe Ala Thr Glu Leu 5360 5365
5370 Phe Glu Gln Lys Thr Met Gln Gly Met Val Asp Val
Phe Gln Glu 5375 5380 5385
Val Leu Ser Arg Gly Leu Glu Gln Pro Gln Ile Pro Leu Ala Thr 5390
5395 5400 Leu Pro Leu Thr His
Gly Leu Glu Glu Leu Arg Thr Met Gly Leu 5405 5410
5415 Leu Asp Val Glu Lys Thr Asp Tyr Pro Arg
Glu Ser Ser Val Val 5420 5425 5430
Asp Val Phe Arg Glu Gln Ala Ala Ala Cys Ser Glu Ala Ile Ala
5435 5440 5445 Val Lys
Asp Ser Ser Ala Gln Leu Thr Tyr Ser Glu Leu Asp Arg 5450
5455 5460 Gln Ser Asp Glu Leu Ala Gly
Trp Leu Arg Gln Gln Arg Leu Pro 5465 5470
5475 Ala Glu Ser Leu Val Ala Val Leu Ala Pro Arg Ser
Cys Gln Thr 5480 5485 5490
Ile Val Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu 5495
5500 5505 Pro Leu Asp Val Asn
Val Pro Ala Thr Arg Leu Glu Ser Ile Leu 5510 5515
5520 Ser Ala Val Gly Gly Arg Lys Leu Val Leu
Leu Gly Ala Asp Val 5525 5530 5535
Ala Asp Pro Gly Leu Arg Leu Ala Asp Val Glu Leu Val Arg Ile
5540 5545 5550 Gly Asp
Thr Leu Gly Arg Cys Val Pro Gly Ala Pro Gly Asp Asn 5555
5560 5565 Glu Ala Pro Val Val Gln Pro
Ser Ala Thr Ser Leu Ala Tyr Val 5570 5575
5580 Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly
Val Met Val 5585 5590 5595
Glu His Arg Ser Ile Leu Arg Val Val Thr Ser Pro Pro Ala Arg 5600
5605 5610 Ala Leu Leu Pro Ser
Thr Ile Ile Met Ala His Leu Thr Asn Ile 5615 5620
5625 Ala Phe Asp Val Ser Leu Trp Glu Ile Cys
Thr Ala Leu Leu His 5630 5635 5640
Gly Gly Thr Leu Ile Cys Ile Gln Tyr Leu Ala Ser Leu Asp Val
5645 5650 5655 Arg Gly
Leu Gln Thr Thr Phe Ser Arg Glu Ala Ile Asn Val Ala 5660
5665 5670 Val Phe Pro Pro Ala Leu Leu
Lys Thr Cys Leu Ala Lys Ile Pro 5675 5680
5685 Ser Ala Leu Ala Ser Leu Ser Ala Met Phe Ser Ser
Gly Asp Arg 5690 5695 5700
Leu Asp Ser Arg Asp Ala Ser Glu Gly Ala Thr Leu Val Arg Gln 5705
5710 5715 Gly Ile His Asn Ala
Tyr Gly Pro Thr Glu Asn Gly Ile Gln Ser 5720 5725
5730 Thr Ile Tyr Glu Val Lys Ala Asp Ala Glu
Phe Val Asn Gly Val 5735 5740 5745
Pro Ile Gly Arg Ala Val Ser Asn Ser Gly Ala Tyr Val Met Asp
5750 5755 5760 Pro Gln
Gln Gln Leu Val Pro Leu Gly Val Met Gly Glu Leu Val 5765
5770 5775 Val Thr Gly Asp Gly Leu Ala
Arg Gly Tyr Thr Asp Pro Ser Leu 5780 5785
5790 Asp Ala Asp Arg Phe Val Gln Val Ser Val Asn Gly
Gln Leu Val 5795 5800 5805
Arg Ala Tyr Arg Thr Gly Asp Arg Val Arg Cys Arg Pro Cys Asp 5810
5815 5820 Gly Gln Ile Glu Phe
Phe Gly Arg Met Asp Arg Gln Val Lys Ile 5825 5830
5835 Arg Gly His Arg Ile Glu Leu Ala Glu Val
Glu His Ala Ile Leu 5840 5845 5850
Ser Leu Asp Tyr Val Ile Asp Ala Ala Val Leu Leu Arg Gln Leu
5855 5860 5865 Ile Asp
Gln Glu Pro Gln Val Val Gly Phe Val Ile Val Ser Thr 5870
5875 5880 Lys Arg Ala Tyr Ser Arg His
Asn Ser Gly Tyr Ala Ser Glu Val 5885 5890
5895 Ser Ala Phe Cys Ile Lys Asp Gln Ile Ala Trp Arg
Ile Arg Gln 5900 5905 5910
His Leu Cys Arg Met Leu Pro Ser Tyr Met Val Pro Tyr Gln Ile 5915
5920 5925 Ala Ile Leu Asp Glu
Met Pro Ile Asn Ala Asn Gly Lys Val Asp 5930 5935
5940 Arg Gln Asn Leu Ala Ser Arg Thr Val Asn
Val Gln Arg Ile Leu 5945 5950 5955
Ala Ala Pro Tyr Met Ala Pro Arg Asn Glu Val Glu Ile Ser Leu
5960 5965 5970 Cys Glu
Gln Tyr Ala Ala Leu Leu Glu His Asp Val Gly Ile Leu 5975
5980 5985 Asp Asp Phe Phe Glu Leu Gly
Gly His Ser Leu Met Ala Thr Arg 5990 5995
6000 Leu Ala Ser Arg Ile Ser Ser Arg Phe Ser Ala Pro
Val Ser Val 6005 6010 6015
Arg Asp Ile Phe Asp His Pro Arg Ile Met Asp Leu Ala Ser Ile 6020
6025 6030 Ile Arg Ala Gly Asp
Ile Gln Trp Ser Arg Ile Leu Pro Ser Ala 6035 6040
6045 Tyr Glu Arg Pro Val Glu Gln Ser Phe Ala
Gln Asn Arg Leu Trp 6050 6055 6060
Phe Leu Tyr Lys Leu Asp Ile Gly Thr Thr Gln Tyr Asn Leu Pro
6065 6070 6075 Leu Ala
Ile His Leu Arg Gly Pro Leu Asp Ile Ser Ala Leu Phe 6080
6085 6090 Ile Ala Phe Lys Ala Leu Thr
Glu Arg His Glu Leu Leu Arg Thr 6095 6100
6105 Thr Phe Asp Glu Asp Asp Gly Thr Cys Leu Gln Met
Leu Leu Pro 6110 6115 6120
Glu Tyr Gln His Glu Val Arg Ile Thr Asp Leu Gln Gly Ser His 6125
6130 6135 Lys Gly Ser Leu Leu
Asp Ile Leu Asn Asn Asn Gln Lys Thr Pro 6140 6145
6150 Phe Glu Leu Ser Arg Glu Pro Gly Trp Arg
Val Ala Leu Leu Arg 6155 6160 6165
Leu Gly Asp Asp Asp His Val Leu Ser Ile Val Met His His Ile
6170 6175 6180 Ile Ser
Asp Gly Trp Ser Val Asp Val Leu Arg His Glu Leu Gly 6185
6190 6195 Gln Phe Tyr Ser Ala Ala Leu
Arg Gly Gln Asp Pro Leu Ser Gln 6200 6205
6210 Ile Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe Ala
Leu Trp Gln 6215 6220 6225
Arg Gln Asp Glu Gln Val Ala Glu His Gln Arg Gln Leu Glu His 6230
6235 6240 Trp Thr Glu Gln Leu
Ala Asp Ser Ser Pro Ala Glu Leu Leu Ser 6245 6250
6255 Asp His Pro Arg Pro Ser Ile Leu Ser Gly
Gln Ala Gly Ala Ile 6260 6265 6270
Pro Val Asn Val Gln Gly Ser Leu Tyr Gln Ala Leu Arg Ala Phe
6275 6280 6285 Cys Arg
Ala His Gln Val Thr Ser Phe Val Val Leu Leu Thr Ala 6290
6295 6300 Phe Arg Ile Ala His Tyr Arg
Leu Thr Gly Ala Glu Asp Ala Thr 6305 6310
6315 Ile Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro Glu
Leu Glu Asn 6320 6325 6330
Met Ile Gly Phe Phe Val Asn Thr Gln Cys Met Arg Ile Val Ile 6335
6340 6345 Gly Ser Asp Asp Thr
Phe Glu Gly Leu Val Gln Gln Val Arg Ser 6350 6355
6360 Ile Thr Ala Ala Ala His Glu Asn Gln Asp
Val Pro Phe Glu Arg 6365 6370 6375
Ile Val Ser Ala Leu Leu Pro Gly Ser Arg Asp Thr Ser Arg Asn
6380 6385 6390 Pro Leu
Val Gln Leu Met Phe Ala Val His Ser Gln Arg Asn Leu 6395
6400 6405 Gly Gln Ile Ser Leu Glu Gly
Leu Gln Gly Glu Leu Leu Gly Val 6410 6415
6420 Ala Ala Thr Thr Arg Phe Asp Val Glu Phe His Leu
Phe Gln Asp 6425 6430 6435
Asp Asp Lys Leu Ser Gly Asn Val Leu Phe Ala Thr Glu Leu Phe 6440
6445 6450 Glu Gln Lys Thr Met
Gln Gly Met Val Asp Val Phe Gln Glu Val 6455 6460
6465 Leu Ser Arg Gly Leu Glu Gln Pro Gln Ile
Pro Leu Ala Thr Leu 6470 6475 6480
Pro Leu Thr His Gly Leu Glu Glu Leu Arg Thr Met Gly Leu Leu
6485 6490 6495 Asp Val
Glu Lys Thr Asp Tyr Pro Arg Glu Ser Ser Val Val Asp 6500
6505 6510 Val Phe Arg Glu Gln Ala Ala
Ala Cys Ser Glu Ala Ile Ala Val 6515 6520
6525 Lys Asp Ser Ser Ala Gln Leu Thr Tyr Ser Glu Leu
Asp Arg Gln 6530 6535 6540
Ser Asp Glu Leu Ala Gly Trp Leu Arg Gln Gln Arg Leu Pro Ala 6545
6550 6555 Glu Ser Leu Val Ala
Val Leu Ala Pro Arg Ser Cys Gln Thr Ile 6560 6565
6570 Val Ala Phe Leu Gly Ile Leu Lys Ala Asn
Leu Ala Tyr Leu Pro 6575 6580 6585
Leu Asp Val Asn Val Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser
6590 6595 6600 Ala Val
Gly Gly Arg Lys Leu Val Leu Leu Gly Ala Asp Val Ala 6605
6610 6615 Asp Pro Gly Leu Arg Leu Ala
Asp Val Glu Leu Val Arg Ile Gly 6620 6625
6630 Asp Thr Leu Gly Arg Cys Val Pro Gly Ala Pro Gly
Asp Asn Glu 6635 6640 6645
Ala Pro Val Val Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile 6650
6655 6660 Phe Thr Ser Gly Ser
Thr Gly Lys Pro Lys Gly Val Met Val Glu 6665 6670
6675 His Arg Gly Val Val Arg Leu Val Lys Gln
Ser Asn Val Val Tyr 6680 6685 6690
His Leu Pro Ser Thr Ser Arg Val Ala His Leu Ser Asn Leu Ala
6695 6700 6705 Phe Asp
Ala Ser Val Leu Glu Ile Tyr Ala Ala Leu Leu Asn Gly 6710
6715 6720 Gly Thr Val Tyr Cys Ile Asp
Tyr Leu Thr Thr Leu Asp Pro His 6725 6730
6735 Ala Leu Glu Ser Val Phe Ile Asp Ala Asp Leu Asn
Thr Ala Val 6740 6745 6750
Leu Pro Pro Ala Leu Leu Lys Gln Val Leu Ala Ser Ser Pro Ser 6755
6760 6765 Thr Leu His Ala Leu
Asp Leu Leu Phe Ile Gly Gly Asp Arg Leu 6770 6775
6780 Asp Ala Arg Asp Ala Leu Tyr Ala Asn Arg
Leu Val Arg Gly Ser 6785 6790 6795
Leu Tyr Asn Val Tyr Gly Pro Thr Glu Asn Thr Val Leu Ser Val
6800 6805 6810 Val Tyr
Leu Phe Asn Asp Asp Asp Ala Cys Ile Asn Gly Val Pro 6815
6820 6825 Ile Gly Gln Val Val Ser Asn
Ser Gly Val Tyr Val Met Asp Ser 6830 6835
6840 Glu Gln Lys Leu Val Pro Pro Gly Val Met Gly Glu
Ile Val Val 6845 6850 6855
Thr Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Ser Thr Leu Asn 6860
6865 6870 Thr Asp Arg Phe Val
Gln Ile Ser Val Asn Gly Arg Val Leu Gln 6875 6880
6885 Ala Tyr Arg Thr Gly Asp Arg Gly Arg Tyr
Arg Pro Thr Asp Ala 6890 6895 6900
Arg Leu Glu Phe Phe Gly Arg Leu Asp Gln Gln Ile Lys Leu Arg
6905 6910 6915 Gly His
Arg Val Glu Leu Lys Glu Ile Glu Gln Ala Met Leu Gly 6920
6925 6930 His Asn Ala Val Asp Asp Ala
Gly Val Val Ala Leu Glu Ile Ser 6935 6940
6945 Glu Cys Gln Glu Leu Glu Met Val Gly Phe Val Thr
Leu Arg Asn 6950 6955 6960
Leu Gly Thr Met Glu Ala Thr Asn Asn Leu Ala His Thr Ser Trp 6965
6970 6975 Asn Pro Val Thr Leu
Lys Thr Pro Leu Ala Ser Gln Ile Val Ala 6980 6985
6990 Glu Val Arg Gly Arg Leu Gln Arg Asn Leu
Pro Leu Tyr Met Val 6995 7000 7005
Pro Ala Thr Ile Val Val Leu His Thr Met Pro Val Asn Ala Asn
7010 7015 7020 Gly Lys
Leu Asp Arg Gln Ala Leu Val Lys Ala Ala Met Thr Leu 7025
7030 7035 Pro Lys Thr Ala Pro Leu Val
Trp Met Ala Pro Arg Asn Glu Gly 7040 7045
7050 Glu Thr Ser Leu Cys Glu Glu Leu Thr Asp Ile Leu
Gly Val Asn 7055 7060 7065
Val Gly Ile Thr Asp Asn Phe Phe Asp Leu Gly Gly His Ser Leu 7070
7075 7080 Leu Ala Thr Arg Val
Ala Ala Arg Ile Ser Arg Arg Leu Asp Ala 7085 7090
7095 Leu Val Thr Val Lys Gln Ile Phe Asp His
Pro Val Ile Gly Asp 7100 7105 7110
Leu Ala Ala Ala Ile Gln Gly Gly Ser Val Arg His Leu Pro Ile
7115 7120 7125 Thr Ala
Ser Glu Val Asp Gly Pro Val Gln Gln Ser Phe Ala Gln 7130
7135 7140 Asn Arg Leu Trp Phe Leu Glu
Gln Met Asn Ile Gly Ala Thr Trp 7145 7150
7155 Tyr Ile Val Pro Leu Ala Val Arg Leu Tyr Gly Thr
Leu Arg Val 7160 7165 7170
Glu Ala Leu Asn Ile Ala Leu Arg Thr Ile Gln Gln Arg His Glu 7175
7180 7185 Thr Leu Arg Thr Thr
Phe Glu Glu Leu Asn Gly Ile Ala Val Gln 7190 7195
7200 Arg Cys Asp Ser Thr Cys Gln Gly Gln Leu
Arg Val Val Asp Leu 7205 7210 7215
Val Gly Gln Gly Pro Asp Arg Tyr Arg Glu Ile Leu Asp Val Gln
7220 7225 7230 Gln Thr
Thr Pro Phe Glu Leu Ser Gln Glu Pro Gly Trp Arg Val 7235
7240 7245 Ala Leu Leu Arg Leu Gly Asp
Asp Asp His Val Leu Ser Ile Val 7250 7255
7260 Met His His Ile Ile Ser Asp Gly Trp Ser Val Asp
Val Leu Leu 7265 7270 7275
Arg Glu Ile Gly Gln Phe Tyr Ser Ala Ala Leu Arg Gly Gln Asp 7280
7285 7290 Pro Leu Ser Gln Ile
Ser Pro Leu Pro Ile Gln Tyr Arg Asp Phe 7295 7300
7305 Ala Leu Trp Gln Arg Gln Asp Glu Gln Val
Ala Glu His Gln Arg 7310 7315 7320
Gln Leu Glu His Trp Thr Glu Gln Leu Ala Asp Ser Ser Pro Ala
7325 7330 7335 Glu Leu
Leu Ser Asp His Pro Arg Pro Ser Ile Leu Ser Gly Gln 7340
7345 7350 Ala Gly Ala Ile Pro Val Asn
Val Gln Gly Ser Leu Tyr Gln Ala 7355 7360
7365 Leu Arg Ala Phe Cys Arg Ala His Gln Val Thr Ser
Phe Val Val 7370 7375 7380
Leu Leu Thr Ala Phe Arg Ile Ala His Tyr Arg Leu Thr Gly Ala 7385
7390 7395 Glu Asp Ala Thr Ile
Gly Thr Pro Ile Ala Asn Arg Asn Arg Pro 7400 7405
7410 Glu Leu Glu Asn Met Ile Gly Phe Phe Val
Asn Thr Gln Cys Met 7415 7420 7425
Arg Ile Val Ile Gly Ser Asp Asp Thr Phe Glu Gly Leu Val Gln
7430 7435 7440 Gln Val
Arg Ser Ile Thr Ala Ala Ala His Glu Asn Gln Asp Val 7445
7450 7455 Pro Phe Glu Arg Ile Val Ser
Ala Leu Leu Pro Gly Ser Arg Asp 7460 7465
7470 Thr Ser Arg Asn Pro Leu Val Gln Leu Met Phe Ala
Val His Ser 7475 7480 7485
Gln Arg Asn Leu Gly Gln Ile Ser Leu Glu Gly Leu Gln Gly Glu 7490
7495 7500 Leu Leu Gly Val Ala
Ala Thr Thr Arg Phe Asp Val Glu Phe His 7505 7510
7515 Leu Phe Gln Asp Asp Asp Lys Leu Ser Gly
Asn Val Leu Phe Ala 7520 7525 7530
Thr Glu Leu Phe Glu Gln Lys Thr Met Gln Gly Met Val Asp Val
7535 7540 7545 Phe Gln
Glu Val Leu Ser Arg Gly Leu Glu Gln Pro Gln Ile Pro 7550
7555 7560 Leu Ala Thr Leu Pro Leu Thr
His Gly Leu Glu Glu Leu Arg Thr 7565 7570
7575 Met Gly Leu Leu Asp Val Glu Lys Thr Asp Tyr Pro
Arg Glu Ser 7580 7585 7590
Ser Val Val Asp Val Phe Arg Glu Gln Ala Ala Ala Cys Ser Glu 7595
7600 7605 Ala Ile Ala Val Lys
Asp Ser Ser Ala Gln Leu Thr Tyr Ser Glu 7610 7615
7620 Leu Asp Arg Gln Ser Asp Glu Leu Ala Gly
Trp Leu Arg Gln Gln 7625 7630 7635
Arg Leu Pro Ala Glu Ser Leu Val Ala Val Leu Ala Pro Arg Ser
7640 7645 7650 Cys Gln
Thr Ile Val Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu 7655
7660 7665 Ala Tyr Leu Pro Leu Asp Val
Asn Val Pro Ala Thr Arg Leu Glu 7670 7675
7680 Ser Ile Leu Ser Ala Val Gly Gly Arg Lys Leu Val
Leu Leu Gly 7685 7690 7695
Ala Asp Val Ala Asp Pro Gly Leu Arg Leu Ala Asp Val Glu Leu 7700
7705 7710 Val Arg Ile Gly Asp
Thr Leu Gly Arg Cys Val Pro Gly Ala Pro 7715 7720
7725 Gly Asp Asn Glu Ala Pro Val Val Gln Pro
Ser Ala Thr Ser Leu 7730 7735 7740
Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly Lys Pro Lys Gly
7745 7750 7755 Val Met
Val Glu His Arg Gly Val Val Arg Leu Val Lys Gln Ser 7760
7765 7770 Asn Val Val Tyr His Leu Pro
Ser Thr Ser Arg Val Ala His Leu 7775 7780
7785 Ser Asn Leu Ala Phe Asp Ala Ser Ala Trp Glu Ile
Tyr Ala Ala 7790 7795 7800
Leu Leu Asn Gly Gly Thr Leu Ile Cys Ile Asp Tyr Phe Thr Thr 7805
7810 7815 Leu Asp Cys Ser Ala
Leu Gly Ala Lys Phe Ile Lys Glu Lys Ile 7820 7825
7830 Val Ala Thr Met Ile Pro Pro Ala Leu Leu
Lys Gln Cys Leu Ala 7835 7840 7845
Ile Phe Pro Thr Ala Leu Ser Glu Leu Val Leu Leu Phe Ala Ala
7850 7855 7860 Gly Asp
Arg Phe Ser Ser Gly Asp Ala Val Glu Val Gln Arg His 7865
7870 7875 Thr Lys Gly Ala Val Cys Asn
Ala Tyr Gly Pro Thr Glu Asn Thr 7880 7885
7890 Ile Leu Ser Thr Ile Tyr Glu Val Lys Gln Asn Glu
Asn Phe Pro 7895 7900 7905
Asn Gly Val Pro Ile Gly Arg Ala Val Ser Asn Ser Gly Ala Tyr 7910
7915 7920 Val Met Asp Pro Gln
Gln Gln Leu Val Pro Leu Gly Val Met Gly 7925 7930
7935 Glu Leu Val Val Thr Gly Asp Gly Leu Ala
Arg Gly Tyr Thr Asp 7940 7945 7950
Pro Ser Leu Asp Ala Asp Arg Phe Val Gln Val Ser Val Asn Gly
7955 7960 7965 Gln Leu
Val Arg Ala Tyr Arg Thr Gly Asp Arg Val Arg Cys Arg 7970
7975 7980 Pro Cys Asp Gly Gln Ile Glu
Phe Phe Gly Arg Met Asp Arg Gln 7985 7990
7995 Val Lys Ile Arg Gly His Arg Ile Glu Leu Ala Glu
Val Glu His 8000 8005 8010
Ala Val Leu Gly Leu Glu Asp Val Gln Asp Ala Ala Val Ile Ala 8015
8020 8025 Phe Asp Asn Val Asp
Ser Glu Glu Pro Glu Met Val Gly Phe Val 8030 8035
8040 Thr Ile Thr Glu Asp Asn Pro Val Arg Glu
Asp Glu Thr Ser Gly 8045 8050 8055
Gln Val Glu Asp Trp Ala Asn His Phe Glu Ile Ser Thr Tyr Thr
8060 8065 8070 Asp Ile
Ala Ala Ile Asp Gln Gly Ser Ile Gly Ser Asp Phe Val 8075
8080 8085 Gly Trp Thr Ser Met Tyr Asp
Gly Ser Glu Ile Asp Lys Ala Glu 8090 8095
8100 Met Gln Glu Trp Leu Ala Asp Thr Met Ala Ser Met
Leu Asp Gly 8105 8110 8115
Gln Ala Pro Gly Asn Val Leu Glu Ile Gly Thr Gly Thr Gly Met 8120
8125 8130 Val Leu Phe Asn Leu
Gly Asp Gly Leu Gln Ser Tyr Val Gly Leu 8135 8140
8145 Glu Pro Ser Arg Ser Ala Ala Ala Phe Val
Asn Gln Thr Ile Lys 8150 8155 8160
Ser Leu Pro Thr Leu Ala Gly Asn Ala Glu Val His Ile Gly Thr
8165 8170 8175 Ala Thr
Asp Val Ala Arg Leu Asp Gly Leu Arg Pro Asp Leu Val 8180
8185 8190 Val Val Asn Ser Val Val Gln
Tyr Phe Pro Ser Pro Glu Tyr Leu 8195 8200
8205 Met Glu Val Val Glu Ala Leu Ala Arg Leu Pro Gly
Val Glu Arg 8210 8215 8220
Ile Phe Phe Gly Asp Val Arg Ser Tyr Ala Ile Asn Arg Asp Phe 8225
8230 8235 Leu Ala Ala Arg Ala
Leu His Glu Leu Gly Asp Arg Ala Thr Lys 8240 8245
8250 His Glu Ile Arg Arg Lys Met Leu Glu Met
Glu Glu Arg Glu Glu 8255 8260 8265
Glu Leu Leu Val Asp Pro Ala Phe Phe Thr Met Leu Thr Ser Ser
8270 8275 8280 Leu Pro
Gly Leu Ile Gln His Val Glu Ile Leu Pro Lys Leu Met 8285
8290 8295 Arg Ala Thr Asn Glu Leu Ser
Ala Tyr Arg Tyr Thr Ala Val Val 8300 8305
8310 His Val Cys Arg Ala Gly Gln Glu Pro Arg Ser Val
His Thr Ile 8315 8320 8325
Asp Asp Asp Ala Trp Val Asn Leu Gly Ala Ser Arg Leu Ser Arg 8330
8335 8340 Pro Thr Leu Ser Ser
Leu Leu Gln Thr Ser Glu Gly Ala Ser Ala 8345 8350
8355 Val Ala Val Ser Asn Ile Pro Tyr Ser Lys
Thr Ile Thr Glu Arg 8360 8365 8370
Ala Leu Val Ser Ala Leu Asp Glu Asp Asp Met Gln Asp Ser Ser
8375 8380 8385 Asp Trp
Leu Leu Ala Val Arg Glu Thr Gly Arg Ser Cys Ser Ser 8390
8395 8400 Phe Ser Ala Thr Asp Leu Val
Glu Leu Ala Arg Glu Thr Gly Trp 8405 8410
8415 Arg Val Glu Leu Ser Trp Ala Arg Gln Tyr Ser Gln
Lys Gly Ala 8420 8425 8430
Leu Asp Ala Val Phe His Arg His Pro Val Ser Ala Gly Ser Gly 8435
8440 8445 Arg Val Met Phe Gln
Phe Pro Val Glu Thr Glu Asp Arg Pro His 8450 8455
8460 Ile Ser Arg Thr Asn Arg Pro Leu Gln Arg
Leu Gln Lys Lys Arg 8465 8470 8475
Thr Glu Thr His Val His Glu Gln Leu Arg Ala Leu Leu Pro Arg
8480 8485 8490 Tyr Met
Val Pro Thr Arg Ile Val Ala Leu Asp Lys Leu Pro Val 8495
8500 8505 Asn Ala Asn Gly Lys Val Asp
Arg Gln Gln Leu Ala Arg Thr Ala 8510 8515
8520 Gln Val Leu Pro Ala Ser Lys Ala Pro Ser Ala Cys
Val Ala Pro 8525 8530 8535
Arg Asn Glu Leu Glu Met Thr Leu Cys Glu Glu Phe Ser Gln Val 8540
8545 8550 Leu Gly Val Glu Val
Gly Ile Thr Asp Asn Phe Phe His Leu Gly 8555 8560
8565 Gly His Ser Leu Met Ala Thr Lys Phe Ala
Ala Arg Ile Ser Arg 8570 8575 8580
Arg Leu Asn Ala Ile Val Ser Val Lys Asn Val Phe Asp His Pro
8585 8590 8595 Val Pro
Met Asp Leu Ala Ala Thr Ile Gln Glu Gly Ser Lys Leu 8600
8605 8610 His Thr Pro Ile Pro Arg Thr
Ala Tyr Ser Gly Pro Val Glu Gln 8615 8620
8625 Ser Phe Ala Gln Gly Arg Leu Trp Phe Leu Asp Gln
Phe Asn Pro 8630 8635 8640
Ser Ser Ile Gly Tyr Val Met Pro Phe Ala Ala Arg Leu His Gly 8645
8650 8655 Gln Leu Gln Ile Glu
Ala Leu Thr Ala Ala Leu Phe Ala Leu Glu 8660 8665
8670 Gln Arg His Glu Ile Leu Arg Thr Thr Leu
Asp Ala His Asp Gly 8675 8680 8685
Val Gly Met Gln Ile Val His Ala Glu His Pro Gln Gln Leu Arg
8690 8695 8700 Ile Ile
Asp Val Ser Ala Lys Ala Ser Ser Ser Tyr Ala Gln Thr 8705
8710 8715 Leu Arg Asp Glu Gln Ala Ser
Pro Phe Asp Leu Ser Lys Glu Pro 8720 8725
8730 Gly Trp Arg Val Ser Leu Leu Gln Leu Ser Glu Ile
Asp Tyr Val 8735 8740 8745
Leu Ser Ile Val Met His His Thr Ile Tyr Asp Gly Trp Ser Leu 8750
8755 8760 Asp Val Leu Arg Arg
Glu Leu Ser Gln Phe Tyr Ala Ala Ala Ile 8765 8770
8775 Arg Gly Arg Glu Pro Leu Ser Thr Ile Glu
Pro Leu Pro Ile Gln 8780 8785 8790
Tyr Arg Asp Phe Ser Val Trp Gln Lys Gln Glu Asp Gln Val Ala
8795 8800 8805 Glu His
Arg Arg Gln Leu His Tyr Trp Ile Glu Gln Leu Asp Gly 8810
8815 8820 Ser Ser Pro Ala Glu Phe Leu
Asn Asp Lys Pro Arg Pro Thr Leu 8825 8830
8835 Leu Ser Gly Lys Ala Gly Val Val Glu Ile Ala Val
Lys Gly Thr 8840 8845 8850
Val Tyr Gln Arg Leu Leu Glu Phe Cys Arg Leu His Gln Val Thr 8855
8860 8865 Ser Phe Met Val Leu
Leu Ala Ala Phe Arg Ala Thr His Tyr Arg 8870 8875
8880 Leu Thr Gly Thr Glu Asp Ala Thr Val Gly
Thr Pro Ile Ala Asn 8885 8890 8895
Arg Asn Arg Pro Glu Leu Glu Asn Met Ile Gly Leu Phe Val Asn
8900 8905 8910 Thr Gln
Cys Ile Arg Leu Lys Ile Glu Asp Asn Asp Thr Leu Glu 8915
8920 8925 Glu Leu Val Gln His Val Arg
Ala Thr Ile Thr Ala Ser Ile Ser 8930 8935
8940 Asn Gln Asp Val Pro Phe Glu Gln Val Val Ser Ala
Leu Leu Pro 8945 8950 8955
Gly Ser Arg Asp Thr Ser Arg Asn Pro Leu Val Gln Leu Thr Phe 8960
8965 8970 Ala Val His Ser Gln
Arg Asn Leu Ala Asp Ile Gln Leu Glu Asn 8975 8980
8985 Val Glu Thr Asn Ala Met Pro Ile Cys Pro
Ser Thr Arg Phe Asp 8990 8995 9000
Ala Glu Phe His Leu Phe Gln Glu Glu Asn Met Leu Ser Gly Arg
9005 9010 9015 Val Leu
Phe Ser Asp Asp Leu Phe Glu Gln Lys Thr Met Gln Gly 9020
9025 9030 Met Val Asp Val Phe Gln Glu
Val Leu Ser Arg Gly Leu Glu Gln 9035 9040
9045 Pro Gln Ile Pro Leu Ala Thr Leu Pro Leu Thr His
Gly Leu Glu 9050 9055 9060
Glu Leu Arg Thr Met Gly Leu Leu Asp Val Glu Lys Thr Asp Tyr 9065
9070 9075 Pro Arg Glu Ser Ser
Val Val Asp Val Phe Arg Glu Gln Ala Ala 9080 9085
9090 Ala Cys Ser Glu Ala Ile Ala Val Lys Asp
Ser Ser Ala Gln Leu 9095 9100 9105
Thr Tyr Ser Glu Leu Asp Arg Gln Ser Asp Glu Leu Ala Gly Trp
9110 9115 9120 Leu Arg
Gln Gln Arg Leu Pro Ala Glu Ser Leu Val Ala Val Leu 9125
9130 9135 Ala Pro Arg Ser Cys Gln Thr
Ile Val Ala Phe Leu Gly Ile Leu 9140 9145
9150 Lys Ala Asn Leu Ala Tyr Leu Pro Leu Asp Val Asn
Val Pro Ala 9155 9160 9165
Thr Arg Leu Glu Ser Ile Leu Ser Ala Val Gly Gly Arg Lys Leu 9170
9175 9180 Val Leu Leu Gly Ala
Asp Val Ala Asp Pro Gly Leu Arg Leu Ala 9185 9190
9195 Asp Val Glu Leu Val Arg Ile Gly Asp Thr
Leu Gly Arg Cys Val 9200 9205 9210
Pro Gly Ala Pro Gly Asp Asn Glu Ala Pro Val Val Gln Pro Ser
9215 9220 9225 Ala Thr
Ser Leu Ala Tyr Val Ile Phe Thr Ser Gly Ser Thr Gly 9230
9235 9240 Lys Pro Lys Gly Val Met Val
Glu His Arg Gly Val Val Arg Leu 9245 9250
9255 Val Lys Gln Ser Asn Val Val Tyr His Leu Pro Ser
Thr Ser Arg 9260 9265 9270
Val Ala His Leu Ser Asn Leu Ala Phe Asp Ala Ser Ala Trp Glu 9275
9280 9285 Ile Tyr Ala Ala Leu
Leu Asn Gly Gly Thr Leu Ile Cys Ile Asp 9290 9295
9300 Tyr Phe Thr Ile Ile Asp Ala Arg Ala Leu
Gly Val Ile Phe Ala 9305 9310 9315
Gln Gln Ser Ile Asn Ala Thr Met Leu Ser Pro Leu Leu Leu Lys
9320 9325 9330 Gln Phe
Leu Ser Asp Ala Pro Phe Val Leu Arg Ser Leu His Ala 9335
9340 9345 Leu Tyr Leu Gly Gly Asp Arg
Leu Gln Gly Arg Asp Ala Ile Gln 9350 9355
9360 Ala Cys Arg Val Gly Cys Ala Phe Val Ile Asn Ala
Tyr Gly Pro 9365 9370 9375
Thr Glu Asn Ser Val Ile Ser Thr Thr Tyr Thr Leu Val Lys Gly 9380
9385 9390 Asn Ala Asp Phe Pro
Asn Gly Val Pro Ile Gly Arg Ala Val Ser 9395 9400
9405 Asn Ser Gly Ala Tyr Val Met Asp Pro Gln
Gln Gln Leu Val Pro 9410 9415 9420
Leu Gly Val Met Gly Glu Leu Val Val Thr Gly Asp Gly Leu Ala
9425 9430 9435 Arg Gly
Tyr Thr Asp Pro Ser Leu Asp Ala Asp Arg Phe Val Gln 9440
9445 9450 Val Ser Val Asn Gly Gln Leu
Val Arg Ala Tyr Arg Thr Gly Asp 9455 9460
9465 Arg Val Arg Cys Arg Pro Cys Asp Gly Gln Ile Glu
Phe Phe Gly 9470 9475 9480
Arg Met Asp Arg Gln Val Lys Ile Arg Gly His Arg Ile Glu Leu 9485
9490 9495 Ala Glu Val Glu His
Ala Val Leu Gly Leu Glu Asp Val Gln Asp 9500 9505
9510 Ala Ala Val Leu Ile Ala Gln Thr Ala Glu
Asn Glu Glu Leu Val 9515 9520 9525
Gly Phe Phe Thr Leu Arg Gln Thr Gln Ala Val Gln Ser Asn Gly
9530 9535 9540 Ala Ala
Gly Val Val Pro Glu His Ser Asp Ser Glu Leu Ala Gln 9545
9550 9555 Ser Cys Ser Cys Thr Gln Thr
Glu Arg Arg Val Arg Asn Arg Leu 9560 9565
9570 Gln Ser Cys Leu Pro Arg Tyr Met Val Pro Ser Arg
Met Val Leu 9575 9580 9585
Leu Asp Arg Leu Pro Val Asn Pro Asn Gly Lys Val Asp Arg Gln 9590
9595 9600 Glu Leu Thr Arg Arg
Ala Gln Asp Leu Pro Ile Ser Glu Ser Ser 9605 9610
9615 Pro Val His Val Lys Pro Arg Thr Glu Leu
Glu Arg Ser Leu Cys 9620 9625 9630
Glu Glu Phe Ala Asp Val Ile Gly Leu Glu Val Gly Val Thr Asp
9635 9640 9645 Asn Phe
Phe Asp Leu Gly Gly His Ser Leu Met Ala Met Lys Leu 9650
9655 9660 Ala Ala Arg Ile Ser Arg Arg
Ser Asn Ala His Ile Ser Val Lys 9665 9670
9675 Asp Ile Phe Asp His Pro Leu Ile Ala Asp Leu Ala
Met Lys Ile 9680 9685 9690
Arg Glu Gly Ser Asp Leu His Thr Pro Ile Pro His Arg Met Tyr 9695
9700 9705 Val Gly Pro Ile Gln
Leu Ser Phe Ala Gln Gly Arg Leu Trp Phe 9710 9715
9720 Leu Asp Gln Leu Asn Leu Gly Ala Ser Trp
Tyr Val Met Pro Leu 9725 9730 9735
Ala Met Arg Leu Gln Gly Ser Leu Gln Leu Asp Ala Leu Glu Thr
9740 9745 9750 Ala Leu
Phe Ala Ile Glu Gln Arg His Glu Thr Leu Arg Met Thr 9755
9760 9765 Phe Ala Glu Gln Asp Gly Val
Ala Val Gln Val Val His Ala Ala 9770 9775
9780 His Tyr Lys His Ile Lys Met Ile Asp Lys Pro Leu
Arg Gln Lys 9785 9790 9795
Ile Asp Val Leu Lys Met Leu Glu Glu Glu Arg Thr Thr Pro Phe 9800
9805 9810 Glu Leu Ser Arg Glu
Pro Gly Trp Arg Val Ala Leu Leu Arg Leu 9815 9820
9825 Gly Asp Asp Asp His Val Leu Ser Ile Val
Met His His Ile Ile 9830 9835 9840
Ser Asp Gly Trp Ser Val Asp Val Leu Arg His Glu Leu Gly Gln
9845 9850 9855 Phe Tyr
Ser Ala Ala Leu Arg Gly Gln Asp Pro Leu Ser Gln Ile 9860
9865 9870 Ser Pro Leu Pro Ile Gln Tyr
Arg Asp Phe Ala Leu Trp Gln Arg 9875 9880
9885 Gln Asp Glu Gln Val Ala Glu His Gln Arg Gln Leu
Glu His Trp 9890 9895 9900
Thr Glu Gln Leu Ala Asp Ser Ser Pro Ala Glu Leu Leu Ser Asp 9905
9910 9915 His Pro Arg Pro Ser
Ile Leu Ser Gly Gln Ala Gly Ala Ile Pro 9920 9925
9930 Val Asn Val Gln Gly Ser Leu Tyr Gln Ala
Leu Arg Ala Phe Cys 9935 9940 9945
Arg Ala His Gln Val Thr Ser Phe Val Val Leu Leu Thr Ala Phe
9950 9955 9960 Arg Ile
Ala His Tyr Arg Leu Thr Gly Ala Glu Asp Ala Thr Ile 9965
9970 9975 Gly Thr Pro Ile Ala Asn Arg
Asn Arg Pro Glu Leu Glu Asn Met 9980 9985
9990 Ile Gly Phe Phe Val Asn Thr Gln Cys Met Arg Ile
Val Ile Gly 9995 10000 10005
Ser Asp Asp Thr Phe Glu Gly Leu Val Gln Gln Val Arg Ser Ile
10010 10015 10020 Thr Ala
Ala Ala His Glu Asn Gln Asp Val Pro Phe Glu Arg Ile 10025
10030 10035 Val Ser Ala Leu Leu Pro
Gly Ser Arg Asp Thr Ser Arg Asn Pro 10040 10045
10050 Leu Val Gln Leu Met Phe Ala Val His
Ser Gln Arg Asn Leu Gly 10055 10060
10065 Gln Ile Ser Leu Glu Gly Leu Gln Gly Glu Leu Leu
Gly Val Ala 10070 10075 10080
Ala Thr Thr Arg Phe Asp Val Glu Phe His Leu Phe Gln Asp Asp
10085 10090 10095 Asp Lys
Leu Ser Gly Asn Val Leu Phe Ala Thr Glu Leu Phe Glu 10100
10105 10110 Gln Lys Thr Met Gln Gly
Met Val Asp Val Phe Gln Glu Val Leu 10115 10120
10125 Ser Arg Gly Leu Glu Gln Pro Gln Ile
Pro Leu Ala Thr Leu Pro 10130 10135
10140 Leu Thr His Gly Leu Glu Glu Leu Arg Thr Met Gly
Leu Leu Asp 10145 10150 10155
Val Glu Lys Thr Asp Tyr Pro Arg Glu Ser Ser Val Val Asp Val
10160 10165 10170 Phe Arg
Glu Gln Ala Ala Ala Cys Ser Glu Ala Ile Ala Val Lys 10175
10180 10185 Asp Ser Ser Ala Gln Leu
Thr Tyr Ser Glu Leu Asp Arg Gln Ser 10190 10195
10200 Asp Glu Leu Ala Gly Trp Leu Arg Gln
Gln Arg Leu Pro Ala Glu 10205 10210
10215 Ser Leu Val Ala Val Leu Ala Pro Arg Ser Cys Gln
Thr Ile Val 10220 10225 10230
Ala Phe Leu Gly Ile Leu Lys Ala Asn Leu Ala Tyr Leu Pro Leu
10235 10240 10245 Asp Val
Asn Val Pro Ala Thr Arg Leu Glu Ser Ile Leu Ser Ala 10250
10255 10260 Val Gly Gly Arg Lys Leu
Val Leu Leu Gly Ala Asp Val Ala Asp 10265 10270
10275 Pro Gly Leu Arg Leu Ala Asp Val Glu
Leu Val Arg Ile Gly Asp 10280 10285
10290 Thr Leu Gly Arg Cys Val Pro Gly Ala Pro Gly Asp
Asn Glu Ala 10295 10300 10305
Pro Val Val Gln Pro Ser Ala Thr Ser Leu Ala Tyr Val Ile Phe
10310 10315 10320 Thr Ser
Gly Ser Thr Gly Lys Pro Lys Gly Val Met Val Glu His 10325
10330 10335 Arg Gly Val Val Arg Leu
Val Lys Gln Ser Asn Val Val Tyr His 10340 10345
10350 Leu Pro Ser Thr Ser Arg Val Ala His
Leu Ser Asn Leu Ala Phe 10355 10360
10365 Asp Ala Ser Ala Trp Glu Ile Tyr Ala Ala Leu Leu
Asn Gly Gly 10370 10375 10380
Thr Leu Ile Cys Ile Asp Tyr Phe Thr Thr Leu Asp Cys Ser Ala
10385 10390 10395 Leu Gly
Ala Lys Phe Ile Lys Glu Lys Ile Val Ala Thr Met Ile 10400
10405 10410 Pro Pro Ala Leu Leu Lys
Gln Cys Leu Ala Ile Phe Pro Thr Ala 10415 10420
10425 Leu Ser Glu Leu Val Leu Leu Phe Ala
Ala Gly Asp Arg Phe Ser 10430 10435
10440 Ser Gly Asp Ala Val Glu Val Gln Arg His Thr Lys
Gly Ala Val 10445 10450 10455
Cys Asn Ala Tyr Gly Pro Thr Glu Asn Thr Ile Leu Ser Thr Ile
10460 10465 10470 Tyr Glu
Val Lys Gln Asn Glu Asn Phe Pro Asn Gly Val Pro Ile 10475
10480 10485 Gly Arg Ala Val Ser Asn
Ser Gly Ala Tyr Val Met Asp Pro Gln 10490 10495
10500 Gln Gln Leu Val Pro Leu Gly Val Met
Gly Glu Leu Val Val Thr 10505 10510
10515 Gly Asp Gly Leu Ala Arg Gly Tyr Thr Asp Pro Ser
Leu Asp Ala 10520 10525 10530
Asp Arg Phe Val Gln Val Ser Val Asn Gly Gln Leu Val Arg Ala
10535 10540 10545 Tyr Arg
Thr Gly Asp Arg Val Arg Cys Arg Pro Cys Asp Gly Gln 10550
10555 10560 Ile Glu Phe Phe Gly Arg
Met Asp Arg Gln Val Lys Ile Arg Gly 10565 10570
10575 His Arg Ile Glu Leu Ala Glu Val Glu
His Ala Val Leu Gly Leu 10580 10585
10590 Glu Asp Val Gln Asp Ala Ala Val Ile Ala Phe Asp
Asn Val Asp 10595 10600 10605
Ser Glu Glu Pro Glu Met Val Gly Phe Val Thr Ile Thr Glu Asp
10610 10615 10620 Asn Pro
Val Arg Glu Asp Glu Thr Ser Gly Gln Val Glu Asp Trp 10625
10630 10635 Ala Asn His Phe Glu Ile
Ser Thr Tyr Thr Asp Ile Ala Ala Ile 10640 10645
10650 Asp Gln Gly Ser Ile Gly Ser Asp Phe
Val Gly Trp Thr Ser Met 10655 10660
10665 Tyr Asp Gly Ser Glu Ile Asp Lys Ala Glu Met Gln
Glu Trp Leu 10670 10675 10680
Ala Asp Thr Met Ala Ser Met Leu Asp Gly Gln Ala Pro Gly Asn
10685 10690 10695 Val Leu
Glu Ile Gly Thr Gly Thr Gly Met Val Leu Phe Asn Leu 10700
10705 10710 Gly Asp Gly Leu Gln Ser
Tyr Val Gly Leu Glu Pro Ser Arg Ser 10715 10720
10725 Ala Ala Ala Phe Val Asn Gln Thr Ile
Lys Ser Leu Pro Thr Leu 10730 10735
10740 Ala Gly Asn Ala Glu Val His Ile Gly Thr Ala Thr
Asp Val Ala 10745 10750 10755
Arg Leu Asp Gly Leu Arg Pro Asp Leu Val Val Val Asn Ser Val
10760 10765 10770 Val Gln
Tyr Phe Pro Ser Pro Glu Tyr Leu Met Glu Val Val Glu 10775
10780 10785 Ala Leu Ala Arg Leu Pro
Gly Val Glu Arg Ile Phe Phe Gly Asp 10790 10795
10800 Val Arg Ser Tyr Ala Ile Asn Arg Asp
Phe Leu Ala Ala Arg Ala 10805 10810
10815 Leu His Glu Leu Gly Asp Arg Ala Thr Lys His Glu
Ile Arg Arg 10820 10825 10830
Lys Met Leu Glu Met Glu Glu Arg Glu Glu Glu Leu Leu Val Asp
10835 10840 10845 Pro Ala
Phe Phe Thr Met Leu Thr Ser Ser Leu Pro Gly Leu Ile 10850
10855 10860 Gln His Val Glu Ile Leu
Pro Lys Leu Met Arg Ala Thr Asn Glu 10865 10870
10875 Leu Ser Ala Tyr Arg Tyr Thr Ala Val
Val His Val Cys Arg Ala 10880 10885
10890 Gly Gln Glu Pro Arg Ser Val His Thr Ile Asp Asp
Asp Ala Trp 10895 10900 10905
Val Asn Leu Gly Ala Ser Arg Leu Ser Arg Pro Thr Leu Ser Ser
10910 10915 10920 Leu Leu
Gln Thr Ser Glu Gly Ala Ser Ala Val Ala Val Ser Asn 10925
10930 10935 Ile Pro Tyr Ser Lys Thr
Ile Thr Glu Arg Ala Leu Val Ser Ala 10940 10945
10950 Leu Asp Glu Asp Asp Met Gln Asp Ser
Ser Asp Trp Leu Leu Ala 10955 10960
10965 Val Arg Glu Thr Gly Arg Ser Cys Ser Ser Phe Ser
Ala Thr Asp 10970 10975 10980
Leu Val Glu Leu Ala Arg Glu Thr Gly Trp Arg Val Glu Leu Ser
10985 10990 10995 Trp Ala
Arg Gln Tyr Ser Gln Lys Gly Ala Leu Asp Ala Val Phe 11000
11005 11010 His Arg His Pro Val Ser
Ala Gly Ser Gly Arg Val Met Phe Gln 11015 11020
11025 Phe Pro Val Glu Thr Glu Asp Arg Pro
His Ile Ser Arg Thr Asn 11030 11035
11040 Arg Pro Leu Gln Arg Leu Gln Lys Lys Arg Thr Glu
Thr His Val 11045 11050 11055
His Glu Gln Leu Arg Ala Leu Leu Pro Arg Tyr Met Val Pro Thr
11060 11065 11070 Arg Ile
Val Ala Leu Asp Lys Leu Pro Val Asn Ala Asn Gly Lys 11075
11080 11085 Val Asp Arg Gln Gln Leu
Ala Arg Thr Ala Gln Val Leu Pro Ala 11090 11095
11100 Ser Lys Ala Pro Ser Ala Cys Val Ala
Pro Arg Asn Glu Leu Glu 11105 11110
11115 Met Thr Leu Cys Glu Glu Phe Ser Gln Val Leu Gly
Val Glu Val 11120 11125 11130
Gly Ile Thr Asp Asn Phe Phe His Leu Gly Gly His Ser Leu Met
11135 11140 11145 Ala Thr
Lys Leu Ala Ala Arg Ile Ser Arg Gln Leu Asn Ile Gln 11150
11155 11160 Val Ser Val Arg Asp Ile
Phe Asp Tyr Pro Val Ile Val Asp Leu 11165 11170
11175 Thr Asp Arg Leu Arg Leu His His Thr
Arg Ile Leu Thr His Asp 11180 11185
11190 His Gly Gln His Gly Gln Pro Asp Leu Lys Pro Phe
Thr Leu Leu 11195 11200 11205
Pro Thr Asn Asn Pro Gln Glu Phe Leu Gln His His Ile Leu Pro
11210 11215 11220 Gln Leu
Val Pro Asp His Ala Lys Ile Leu Asp Val Tyr Pro Val 11225
11230 11235 Thr Arg Ile Gln Arg Arg
Phe Leu His His Pro Lys Arg Gly Leu 11240 11245
11250 Pro Arg Phe Pro Ser Met Val Phe Phe
Asp Phe Pro Pro Gly Ser 11255 11260
11265 Asp Pro His Lys Leu Arg Leu Ala Cys Met Ala Leu
Val Gln Arg 11270 11275 11280
Phe Asp Ile Leu Arg Thr Ile Phe Leu Ser Val Ser Gly Gln Phe
11285 11290 11295 Phe Gln
Val Val Leu Asp Gly Tyr Gly Ile Val Ile Pro Val Ile 11300
11305 11310 Glu Val Asp Glu Glu Leu
Asp Asp Ala Thr Arg Lys Leu His Asp 11315 11320
11325 Ser Asp Ile Gln Gln Pro Leu Arg Leu
Gly Lys Pro Leu Ile Arg 11330 11335
11340 Ile Ala Val Leu Lys Arg Gln His Ser Arg Val Arg
Ala Val Leu 11345 11350 11355
Arg Leu Ser His Ala Leu Tyr Asp Gly Leu Ser Phe Glu His Ile
11360 11365 11370 Ile Gln
Ser Leu His Ala Leu Tyr Leu Asp Ile Thr Leu Ser Ala 11375
11380 11385 Pro Pro Lys Phe Gly Leu
Tyr Val Gln His Met Ile Gln Ser Arg 11390 11395
11400 Ala Glu Gly Tyr Ala Phe Trp Arg Ser
Val Leu Lys Gly Ser Ser 11405 11410
11415 Met Thr Ile Leu Glu Arg Ser Ser Thr Leu Gln Ser
Arg Gln Pro 11420 11425 11430
His Leu Gly Arg Phe Leu Ser Ala Glu Lys Ile Ile Lys Ala Pro
11435 11440 11445 Leu His
Ala Asn Lys Ser Gly Ile Thr Gln Ala Thr Val Phe Ala 11450
11455 11460 Ala Ala Asn Ala Leu Met
Leu Ala Asn Leu Thr Gly Thr Asn Asp 11465 11470
11475 Val Val Phe Ala Arg Ile Val Ser Gly
Arg Gln Ser Leu Pro Lys 11480 11485
11490 Asn Phe Gln His Val Val Gly Pro Cys Thr Asn Asp
Val Pro Val 11495 11500 11505
Arg Val Arg Met Glu Pro Gly Val Gly Pro Lys Ala Leu Leu Arg
11510 11515 11520 Gln Val
Gln Asp Gln Tyr Val His Ser Phe Pro Phe Glu Thr Leu 11525
11530 11535 Gly Phe Asp Glu Ile Lys
Glu Asn Cys Thr Asp Trp Pro Glu Arg 11540 11545
11550 Ile Thr Asn Phe Gly Cys Ser Thr Thr
Tyr Gln Asn Phe Asp Ile 11555 11560
11565 Phe Pro Lys Ser Gln Ile Asp His Gln Gln Ile Gln
Met Ala Ser 11570 11575 11580
Leu Ala Ser Glu Tyr Gln Asn Arg Glu Thr Trp Asp Glu Ala Pro
11585 11590 11595 Leu Tyr
Asp Leu Asn Val Thr Gly Val Pro Gln Pro Asp Gly Arg 11600
11605 11610 His Ile Lys Ile Tyr Val
Gly Val Asp Gly Gln Leu Cys Asp Glu 11615 11620
11625 Ser Thr Leu Asp Cys Ile Leu Ser Asp
Ile Cys Glu Gly Val Val 11630 11635
11640 Ser Leu Thr Asp Ala Leu Gln Glu Leu Pro Ala Ala
Ser Ile Thr 11645 11650 11655
Glu 72103DNAAureobasidium melanogenum strain W5-2 7atggcttcat
ctaatggccc gatgaattcc ccctttgaat tgatccccaa ggtcgtcaat 60aagaagaatt
actatactga cttcttgaag cgcgatgagc aattcctcgc atttcgcctt 120caaggcgagg
agaaccgtaa tcgcatgatc aaagctgcgc gcgataagga ccgcgcaatg 180gctcaggctg
cttctaatgg agtctcagct gatgctgcgc aagctgagat tgacgatgat 240gccgccgagg
atgaagctgc tgaagctgaa gcctttggct caaagacgat tgtcattcat 300cctggcagtc
gcaacctacg tattggtctt gcaacagacg cccttcccaa gacaatcccg 360atggtgattg
cacgcaaggc ttcacatgca gaagacgagg agcctggcgc tgaaccgcgg 420ccaaagcgag
tcaagatgca ggatggtacg gcagagcctg ctggcgagag tgcgttcggc 480gaagatttcg
caaaggaata cagtagcatg gcagctgact tcaaaatcta ccgtcgcaac 540aacaaacgta
gagtcttgcc caactcgcgt gaactggtcg tcaactggaa ctcgcgcaat 600gctccggaaa
ccatttctga acataacgat cctcagcgtg ttgactggac agaaattgtg 660tcacctgcac
ccgaaatctt cactggacat gcagctctgc gaataccaca gcattccaaa 720ccccgataca
gactctactg gccactcaaa tgtggttggc tcaatgaaca agactattcg 780agcaaatcta
gcttatttcg cgacttcttc agcatcatcg aagaggccat caagaacgag 840cttcacctga
accgtaagag agactgggca cagtactctt gcgtgttcat cattcccgat 900ctgtacgaga
aagttttcgt gacatccatc ctcgaggaaa tgttcagaga cttcggtttc 960cagcgtgttt
gcttcatcca agaaagtctg gcagcaacct ttggagctgg atactcgagc 1020agttgtattg
ttgatgttgg tgcacaaaag acttctatct gctgcgttga ggaaggcatg 1080tgcgtcgaga
actcccgcat gaacctgaag tttggcggag aagatgttac agaaacattc 1140atcaagatga
tgctgtacga ccacttcaat tatgccaaca tggatctgct gaggagacat 1200gactaccttc
ttgcggaaga gctgaagcaa aagttctgca cgctcgagga tgcacatatc 1260agcgtacagc
tttatgagtt ccatctccgt gcgttcggcc aagacactcg caaataccag 1320ttcaagacgt
atgatgaagt catgctggca cctatgggtt tcttcaggcc aacaatattt 1380gatcattcag
acaagctcgc tggcagacgc aagctcatcg gtcgctcaac tgacacttac 1440gatgataaac
ctaatgatcc catgtcactc gctcaactgc aggtctacaa gtactcgtcc 1500gataatgttc
cctcagctgt agcagaatca agtacaccgg cacctggtgg cgtgcctgca 1560acacccagca
aacccttgaa cctggaccgc ctaacgcatc ttgccgatgt agcggaaagt 1620acacctcgtt
cctctccagc aggatcgcct gctcctgacg acacggcaac accagtacca 1680ggagctggag
acgcaacacc agccgtagca ggtggcggga tcgaaggtgc acagccaaat 1740actgaagatg
tgctgcctgt gatgcccttg gatcaagcaa tcgtcacatg catcaccgaa 1800ggcgccaagg
gtgatgagaa gaagacgcgt gacttcttcg gtggtatcat ggtgatcgga 1860ggcggtagca
agacttacaa tttcaacgtc tatctcgagc agagacttcg cgcgctacag 1920ccaaacttcc
agaaggaaat cttggttgga cctccgccta gagagctcga tcctcaggtt 1980ctggtgtgga
agggcggtag tgtgtttggc aagatgagag gcactaatga cagctggatc 2040ggacagttgg
agtttgacag actgggtgcc agaatcttga accagaagtg tatgtgggca 2100tac
210381377DNAAureobasidium melanogenum strain W5-2 8atgggtaagg aaaagtccca
cattaacgtc gtcgttatcg gccacgtcga ctccggtaag 60tcgaccacca ccggtcactt
gatctacaag tgcggtggta tcgacaagcg taccatcgag 120aagttcgaga aggaagccgc
cgaactcggc aagggttcct tcaagtacgc ctgggtcctc 180gacaagctga agtctgagcg
tgagcgtggt atcactatcg atatcgccct gtggaagttc 240gagaccccca agtacatggt
caccgtcatc gacgcccccg gtcaccgtga tttcatcaag 300aacatgatca ctggtacctc
gcaggctgac tgcgccattc tcatcattgc cgccggtact 360ggtgagttcg aggctggtat
ctccaaggat ggccagaccc gtgagcacgc ccttctcgcc 420tacaccctcg gtgtcaagca
gctcatcgtt gccatcaaca agatggacac caccaagtgg 480tccgaggccc gttaccagga
gatcatcaag gagacctccg gtttcatcaa gaaggtcggc 540tacaacccca agcacgttcc
cttcgtcccc atctccggtt tcaacggtga caacatgatc 600gaggtttcca ccaactgccc
ctggtacaag ggttgggaga aggagaccaa ggccaaggcc 660accggcaaga ctctcctcga
agccattgac gccatcgacc ctcctacccg ccccaccgac 720aagcccctcc gtcttcccct
ccaggatgtc tacaagatcg gtggtattgg cacggtgccc 780gtcggccgtg tcgagaccgg
taccatcaag ggtggtatgg tcgtcacctt cgcccccgct 840ggtgtcacca ctgaggtcaa
gtccgtcgag atgcaccacg agcagctcgc cgagggtctt 900cccggtgaca acgtcggctt
caacgtcaag aacgtctccg tcaaggagat ccgtcgtggt 960aacgttgccg gtgactccaa
gaacgacccc cccaagggtt gtgactcctt caacgcccag 1020gtcatcgtcc tgaaccaccc
cggtcaggtc ggtgctggtt acgcacccgt cctcgactgc 1080cacactgccc acatcgcctg
caagttctcc gagcttgttg agaagatcga ccgccgtacc 1140ggcaagtccg ttgaggccgc
ccccaagttc atcaagtctg gtgacgccgc cattgtcaag 1200atggttccct ccaagcccat
gtgtgttgag gccttcactg actaccctcc tctcggtcgt 1260ttcgccgtcc gtgacatgag
acagaccgtc gccgtcggtg tcatcaagtc tgtcgccaag 1320tccgacaagg gtggtgccgg
taaggtcact aaggccgccg tcaaggctgg caagaag 137791341DNAAureobasidium
melanogenum strain W5-2 9atgcgtgaga ttgtccacct ccagaccggc caatgcggta
accaagttgg tgctgccttc 60tggcagacca tctctggcga gcacggcctt gacggtgctg
gtgtctacaa cggtacctca 120gatctccagc tggagcgcat gaacgtctac ttcaacgagg
cctctggtaa caaatatgtt 180ccccgtgccg tcctcgtcga cttggagcct ggtaccatgg
acgccgtccg tgctggtcct 240ttcggtcagc tcttccgtcc cgacaacttc gtcttcggtc
agtccggtgc tggcaacaac 300tgggccaagg gtcactacac tgagggtgcc gagttggtcg
accaggtctt ggatgtcgtt 360cgtcgtgagg ccgagagctg tgactgcctc caaggtttcc
agatcactca ctcgctcggt 420ggtggtaccg gtgccggtat gggaacgctc ctcatctcca
agatccgtga ggagttcccc 480gaccgtatga tggccacctt ctccgtcatg ccctccccca
aggtctccga caccgttgtc 540gagccttaca acgctaccct ctccgtccac cagctggtcg
agaactctga cgagaccttc 600tgtatcgaca accaggctct ctacgacatc tgcatgagca
ccctcaagct caacaacccc 660tcctacggcg acctgaacta cctcgtctcc gccgtcatgt
ccggtgttac cgtctcgctc 720cgtttccctg gccagctcaa ctccgacttg cgcaagctcg
ccgtcaacat ggtccccttc 780ccccgtctcc acttcttcat ggtcggtttt gctcctctca
ccagccgtaa cgcccactcg 840ttccgcgccg tctcggttcc cgagctcacc cagcaaatct
tcgaccccaa gaacatgatg 900gccgccaccg atttccgcaa cggccgctac ctgacctgct
ctgccatctt ccgtggtaag 960gtctccatga aggaggtcga ggaccagatg cgcaacgtcc
agaacaagaa ctccgcctac 1020ttcgttgagt ggatccccaa caacgtccag accgccctct
gctccattcc tcctcgtggt 1080cttaagatgt catcgacctt cgtcggtaac tcgacctcga
tccaggagct gttcaagcgt 1140gtcggtgacc agttctctgc catgttccgt cgcaaggctt
tcttgcactg gtacactggt 1200gagggtatgg acgagatgga gttcactgag gctgagtcta
acatgaacga cttggtcagc 1260gagtaccagc agtaccagga ggcttccatc tccgagggtg
aggaggagta cgacgaggag 1320gctcctatgg aggctgagga g
1341106093DNAAureobasidium melanogenum strain W5-2
10cggccggcgc cttgcaacat caacgcccgt catatcctcg acctcaccct tgctgctacc
60acgccctcac caaccgcatc gccgcgcatc acctccattg cgcgcaatcg ccgtctcgag
120tcgcgtcgct ccttcatcgc ctgtcgattt ctctgtttcg ccgctgtccg cctgcgcgcg
180cgccgttcga aaggccagtc gctcgacacg cgctcttccg ccagaggcaa ccctcttaca
240tccacaatca tccaccttat caccactttc atctgtcctg gagatccacg ctcaacctct
300ccgtcgacag cgccctgaag gcggcagccg ctgatacgat tcttacacaa tttctcttag
360ctattgctat caacatccgc caccatgaac atccactctt ttccctattc cagcgctccg
420ctgaagacca ttcaggagat tcagtttggt ctcttctctc ctgaggagat caagaacatg
480agtgtgtgtc acatcgagta cccagagacc atggacgagc aacggatgcg tccgcgagag
540aagggcttaa acgaccccaa gctgggctct atcgatcgct cagttgcctg tggtacctgc
600ggtgaagaca tgctggagtg tcccggtcac tttggtcata ttgagcttgc tgtgcccgtc
660ttccacgtcg gttttgtcac caagatcaag aagattctcg aaaccgtctg ccacaactgt
720ggcaaagtct tgcttgatga aagcattcct gccttcgccc aagctgtccg cataagagat
780cccaagcgcc gcttcgatgc tgttcacaga ctgtgcaagg ccaagacgac ctgcgatccc
840gatgaggctg gtgacgatgg agaagacccg aaagacgcct tgaagaaggg caagcgatca
900cacggtggct gcggtaacct gcaacccaca attcgcaagg acggtcttaa gcttaccggc
960acctacacat accccaagga cgccgataca gaacaaaagc ccgtggagaa gaaggtcatc
1020acccctcaga tggcactgaa cgttttccgc aacatttcga catacgactt ggccagaatg
1080ggcctcaacg cagactacgc tcgtcccgaa tggatgatcc tgaccgtgtt gcccgtaccg
1140ccaccagctg ttcgtcccag tgtttcggtc gatggaacca accaaggaat gcgttccgag
1200gatgatttga ctttcaaact cagtgatatt atccgcgcca atgccaacgt tcgcaagtgt
1260gagctcgagg gctctccaca ccacgttatt gcagagtttg aggctttgct gcagttccac
1320gtcgctacat acatggacaa cgatattgca ggacagccta aggctctgca aaaatccggt
1380agacctgtca aggctattcg tgcgcgcctg aagtccaagg agggtcgtct tcgtggtaac
1440cttatgggca agcgtgtcga tttctccgct cgtacagtca tcactggtga cccgaacttg
1500tctctggatg aagtaggtgt tcctagaagt accgcccgca tccttacctt ccccgagacc
1560gtcaacgctt tcaacatcga caagctacaa caactcgtcc gcaacggtcc caacgaacac
1620cctggagcaa agtatgtcat tcgagacact ggcgagcgca tcgatttgcg ccatcacaag
1680cgcgctggcg agattcaact gcaatatggc tacaaagtcg aaagacatat cgtcgatggt
1740gatgttatta tcttcaaccg tcaaccttcg ctgcacaagg agtctatgat gggtcacaga
1800gtccgtgtca tgccctactc tactttccgt ctcaaccttt ccgttacttc gccatacaac
1860gccgatttcg atggtgatga gatgaacttg cacgttcctc agagtcacga aactcgctca
1920gaagtcatga acctttgcat ggttcccctc aacatcgtct ctcctcagcg taacggtccc
1980ttgatgggta tcgtgcaaga cactctttgt ggtatctaca agatgtgccg tcgtgatgtt
2040ttcctggacc aggaacacgt catgaacatt ctcatgtggg tgcctgattg ggacggtgtc
2100atcccaccac cttctatcct caaacctcgc cctagatgga ctggtaagca gattatcagc
2160ttgatcgtcc ccactggttt gaaccttgtt cgtggtgatg ctgagggcat gcatcccctc
2220aacgacaacg gtttgatggt acatggtggc gagctcatgt acggtctgtt cagcaagaag
2280tccgtcggtg ccagtggagg tggtatcatc cacatcgtct acaacgaaaa gggctgggaa
2340gctgctgtca gtttcttcaa cggagctcag cgtgtcgtca actactggct gctccacaac
2400ggtttcagta tcggtattgg tgacacagtt cctgacgagg cgactgccga ggccatcaca
2460gacgcagtca atgagcagaa ggcagaagta gctgtcatca ccgaggctgc tactgctaac
2520gagcttgaag ctctgcctgg tatgaacgtt cgtgagacgt tcgagagcag agtgtccaag
2580gctttgaaca gtgctcgtga caacgctggt gaccgtacgg aaaagagttt gaaggatttg
2640aacaacgcca ttcagatggc tcgttcaggt tccaagggtt cggctatcaa catttcgcag
2700atgaccgctg tcgtcggcca acaatccgtc gagggaaagc gtattccttt cggcttcaag
2760tacagatcgc ttccccactt caccaaggac gattactctc ccgagtctcg tggtttcgtc
2820gagaactcct atctccgcgg attgacacct tcagaattct tcttccacgc catggctggt
2880cgtgagggtc tgatcgatac tgctgtcaag actgccgaaa ctggttacat tcagcgtcgt
2940ctcgtcaagg ctcttgaaga agtcatggcc aagtatgatg gcactgttcg taactccttg
3000ggcgatatcg tgcaattcgt ctacggtgaa gatggtttgg atgctgtgca tatcgaaggt
3060caaaagttgg atatcatcaa ctgctccgac agtcaattcg agaagaagtt ccgtattgat
3120gtcatggacc ccaagatgtc tctttcaccc gacattctcg agcaagcaca cgagattgct
3180ggagatgttg aggtccagcg tcacctcgac gctgagtatg aagcattgtt ggctgacaga
3240gctctgctca gagatggccg taccgatgac gaagaaaccc accaacttcc tcttaacatc
3300acccgtatcg tcgagagtgc taagaccaga ttccgcatca aggatggcgc tcgcagtgat
3360cttcacccgt ccgacgttat tcccaaggtt cagaacttgc ttgaccagat tgttgttgtt
3420cgtggtgacg accctctttc ccaagaagca caatacaacg ccactatcct cttcaaggcc
3480ctgctcagat cacgtctcgc ttttaagcgt ctggtcaagg agtactcttt gaacaagctc
3540gcgcttgaca acattcttgg tgatattctg aacagattct caagatcgct tgtcagtccc
3600ggtgaaatgg ttggtgtctt ggccgcacag tctattggag aacccgcaac acagatgacg
3660ctcaacactt tccatttcgc tggtgtctcg tccaagaacg ttaccctcgg tgtgccccgt
3720ctgaaggaaa ttctgaacgt tgctaccaac atcaagacac cttccatgac tgtctaccaa
3780tctgccgaaa accgccttga tcaggaagct tgcaagcgac ttcgtagtct ggttgagtac
3840accagtttgc gctccattac tgagaagacc gaaatttggt tcgaccctga cattcaatca
3900accgttgttg aacaagacag ggatatggtc gagtcttact tcatcatccc cgaagagaat
3960gcagagagtc ccgagactta ctccaagtgg ttgctgcgta tcgttcttgg tcgtagacag
4020cttttggaca agggtctttc ggtcgctgat gtcgccgctg ctatcaagaa tgtctaccac
4080caggagatgt ctattatctt cagtgacgac aacgctgatg agcttgttat tcgtatcaga
4140ccttcgaacg tgcttatgga gtccaaagaa gacgatgata ccgctcttga ggccgatctg
4200atcatcggaa gactcgaaac tcatctgttg gacgagacca gacttcgtgg tgtcttgggc
4260gtcgatcgtg ctttcgtcaa cttcaaggaa cgtctgcgcg tcaaggaaga cggtgctctt
4320actatgtcca agagcgatcc tctttgcaag gaatggttct tggataccag cggaactgct
4380ctcaaggaag ttcttactgt tgagggcact gatcctaccc gcacttacac taaccacttc
4440attgacatct tcagtgtgtt cggtattgag gctactagat ccgcattgat gagagaactc
4500aagcaagtgc tttcgttcga cggttcttat gtcaaccatc gccatcttgc cctcctggtc
4560gatattatga ccgctcgcgg taaccttatg gctgtcaccc gtcacggtat caaccgtgct
4620gacactggtg cactgatgcg ttgttcgttc gaagagacgg tcgagattct gttcgaagct
4680gcctcctcag gtgaacttga cgactgccgt ggtgtttccg aaaacatcat tcttggtcag
4740cttgcacctt cgggtactgg tgagtttgat gttcttttgg accagcagat gctcagcact
4800gttgtctctc gtcaccatgg tatgggtgct ggtactcaag ctggcgccgc tcctcttgac
4860ggtgctatga ctccctacga tatgggctct cctcttgccg agggcgacta cggtactgcg
4920gactatggtg cttccttctc tcctatggtc caggcaggtg gcgacgagat gggtggtttc
4980tctgcctacc aaggtggaag cttcagccct tacagtggcg gtcagagccc tggttacgca
5040cctaccagtc cattcagcat gggtacaagc ccatcatctc ccggatatgc ctcgccatct
5100tctcctggct attcacccag atcacctggt gcagctcttg gcagccccgg ctacggcatg
5160ggttcacctg ccagtccggc gtacaaccca acatcgccca cttactcgcc tacatctcct
5220gcctacggca agggctctcc cacctcacct tcttactctc ctacatctcc cagctattcg
5280ccaacttcac ccagctactc gcctacgtcg cctagctact ctcctacctc tccttcatac
5340agccccactt ctcctgctca cagaggatcg ggcatttctc caacctctcc acgatacagc
5400ccgacatctc cggcttactc gcccacttca cctgcataca gcccgaccag cccctcctac
5460aaccctggcg gagcctcgca ctcgcctacg tcgcccagct acagcccgac gtcgccagtg
5520tacagcccaa ccagtccggc acagcagggc tattctccta cctcaccaca gtacactccc
5580aactctcctg gtcaagcttc gcctaagtat tcacctacta gccccaagta ctcgcccaac
5640tcgcctggcc aataagcgaa tgaagcgagc agttacccaa ctgggacgta ccctttgctg
5700ggcccacgtc ttgtcatggg ctagggttaa tatcaaggtc accaacattc cgaaacaact
5760cgtagtctgg gttttggttc acgaagacga tgcacgagcg ataagagcac aagcaggtac
5820attgcgggag attttacaag gcgttcttct ttttcttttt ctgctagtct tgtttttgag
5880agaaggaaag ttctccaagg tttgtttttc aggctcacaa aattgcatat ggagaacgag
5940ccaagtgtag tatcagagag gatttttcga ggcaaagata aaccaaagat gagataacac
6000aaatgcgaac aagcaagtcc aaatttctgc tttcgttgaa agtgactgct ggccgagggc
6060aaaaagcaag tgtaatattt ttttatgtag tcg
6093
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