Methods of increasing the production of cobalamins using cob gene expression

This is a continuation of application Ser. No. 07/916,151, filed on Sep. 14, 1992 now abandoned which is a 371 of PCT/FR91/00054 filed Jan. 30, 1991.

The present invention relates to new polypeptides involved in the biosynthesis of cobalamins and/or cobamides, and especially of coenzyme B 12 . It also relates to the genetic material responsible for the expression of these polypeptides, as well as to a method by means of which they may be prepared. It relates, lastly, to a method for amplification of the production of cobalamins, and more especially of coenzyme B 12 , by recombinant DNA techniques.

Vitamin B 12 belongs to the B group of vitamins. It is a water-soluble vitamin which has been identified as the factor enabling patients suffering from pernicious anaemia to be treated. It is generally prescribed to stimulate haematopoiesis in fatigue subjects, but it is also used in many other cases comprising liver disorders and nervous deficiencies or as an appetite stimulant or an active principle with tonic activity, as well as in dermatology (Berck, 1982, Fraser et al., 1983). In the industrial rearing of non-ruminant animals, the feed being essentially based on proteins of vegetable origin, it is necessary to incorporate vitamin B 12 in the feed rations in amounts of 10 to 15 mg per tonne of feed (Barrère et al., 1981).

Vitamin B 12 belongs to a class of molecules known as cobalamins, the structure of which is presented in FIG. 1 . Cobamides differ from cobalamins in the base of the lower nucleotide, which is no longer 5,6-dimethylbenzimidazole but another base, e.g. 5-hydroxybenzimidazole for vitamin B 12 -factor III synthesised, inter alia, by Clostridium thermoaceticum and Methanosarcina barkeri (Iron et al., 1984). These structural similarities explain the fact that the metabolic pathways of biosynthesis of cobalamins and cobamides are, for the most part, shared.

Cobalamins are synthesised almost exclusively by bacteria, according to a complex and still poorly understood process which may be divided into four steps (FIG. 2 ):

i) synthesis of uroporphyrinogen III (or uro'gen III), then

ii) conversion of uro'gen III to cobyrinic acid, followed by

iii) conversion of the latter to cobinamide, and

iv) construction of the lower nucleotide loop with incorporation of the particular base (5,6-dimethylbenzimidazole in the case of cobalamins).

For coenzyme B 12 , it is probable that the addition of the 5′-deoxyadenosyl group occurs shortly after the corrin ring-system is synthesised (Huennekens et al., 1982).

In the case of cobamides, only the step of synthesis and incorporation of the lower base is different.

The first part of the biosynthesis of cobalamins is very well known, since it is common to that of haemes as well as to that of chlorophylls (Battersby et al., 1980). It involves, successively, δ-aminolevulinate synthase (EC 2.3.137), δ-aminolevulinate dehydrase (EC 4.2.1.24), porphobilinogen deaminase (EC 4.3.1.8) and uro'gen III cosynthase (EC 4.2.1.75), which convert succinyl-CoA and glycine to uro'gen III. However, the first step takes place in some organisms [e.g. E. coli (Avissar et al., 1989) and in methanogenic bacteria (Kannangara et al., 1989), for example] by the conversion by means of a multi-enzyme complex of glutamic acid to δ-aminolevulinic acid.

Between uro'gen III and cobyrinic acid, only three intermediate derivatives have been purified to date; they are the factors FI, FII and FIII, which are oxidation products, respectively, of the three intermediates precorrin-1, precorrin-2 and precorrin-3, which correspond to the mono-, di- and trimethylated derivatives of uro'gen III (FIG. 3 ); these intermediates are obtained by successive transfers of methyl groups from SAM (S-adenosyl-L-methionine) to uro'gen III at positions C-2, C-7 and C-20, respectively. The other reactions which take place to give cobyrinic acid are, apart from five further transfers of methyl groups from SAM at C-17, C-12, C-1, C-15 and C-5, elimination of the carbon at C-20, decarboxylation at C-12 and insertion of a cobalt atom (FIG. 4 ). These biosynthetic steps have been deduced from experiments performed in vitro on acellular extracts of Propionibacterium shermanii or of Clostridium tetanomorphum . In these extracts, cobyrinic acid is obtained by conversion of uro'gen III after incubation under suitable anaerobic conditions (Batterby et al., 1982). No intermediate between precorrin-3 and cobyrinic acid capable of being converted to corrinoids by subsequent incubation with extracts of cobalamin-producing bacteria has been isolated to date. The difficulty of isolating and identifying these intermediates is linked to

i) their great instability,

ii) their sensitivity to oxygen, and

iii) their low level of accumulation in vivo.

In this part of the pathway, only one enzyme of Pseudomonas denitrificans has been purified and studied; it is SAM:uro'gen III methyltransferase (Blanche et al., 1989), referred to as SUMT.

Between cobyrinic acid and cobinamide, the following reactions are performed:

i) addition of the 5′-deoxyadenosyl group (if coenzyme B 12 is the compound to be synthesised),

ii) amidation of six of the seven carboxyl functions by addition of amine groups, and

iii) amidation of the last carboxyl function (propionic acid chain of pyrrole ring D) by addition of (R)-1-amino-2-propanol (FIG. 2 ).

Whether there was really an order in the amidations was not elucidated (Herbert et al., 1970). Lastly, no assay of activity in this part of the pathway has been described, except as regards the addition of the 5′-deoxyadenosyl group (Huennekens et al., 1982).

The final step of the biosynthesis of a cobalamin, e.g. coenzyme B 12 , comprises four successive phases described in FIG. 5 (Huennekens et al., 1982), namely:

i) phosphorylation of the hydroxyl group of the aminopropanol residue of cobinamide to cobinamide phosphate, then

ii) addition of a guanosine diphosphate by reaction with guanosine 5′-triphosphate; the compound obtained is GDP-cobinamide (Friedmann, 1975), which

iii) reacts with 5,6-dimethylbenzimidazole, itself synthesised from riboflavin, to give adenosylcobalamin 5′-phosphate (Friedmann et al., 1968), which

iv) on dephosphorylation leads to coenzyme B 12 (Schneider and Friedmann, 1972).

Among bacteria capable of producing cobalamins, the following may be mentioned in particular:

Agrobacterium tumefaciens

Agrobacterium radiobacter

Bacillus megaterium

Clostridium sticklandii

Clostridium tetanomorphum

Clostridium thermoaceticum

Corynebacterium XG

Eubacterium limosum

Methanobacterium arbophilicum

Methanobacterium ivanovii

Methanobacterium ruminantium

Methanobacterium thermoautotrophicum

Methanosarcina barkeri

Propionobacterium shermanii

Protaminobacter ruber

Pseudomonas denitrificans

Pseudomonas putida

Rhizobium meliloti

Rhodopseudomonas sphaeroides

Salmonella typhimurium

Spirulina platensis

Streptomyces antibioticus

Streptomyces aureofaciens

Streptomyces griseus

Streptomyces olivaceus

At the industrial level, as a result of the great complexity of the biosynthetic mechanisms, the production of cobalamins, and especially of vitamin B 12 , is exclusively microbiological. It is carried out by large-volume cultures of the bacteria Pseudomonas denitrificans, Propionibacterium shermanii and Propionibacterium freudenreichii (Florent, 1986). The strains used for the industrial production are derived from wild-type strains; they may have undergone a large number of cycles of random mutation and then of selection of improved clones for the production of cobalamins (Florent, 1986). The mutations are obtained by mutagenesis with mutagenic agents or by physical treatments such as treatments with ultraviolet rays (Barrère et al., 1981). By this empirical method, random mutations are obtained and improve the production of cobalamins. For example, it is described that, from the original strain of Pseudomonas denitrificans initially isolated by Miller and Rosenblum (1960, U.S. Pat. No. 2,938,822), the production of this microorganism was gradually increased in the space of ten years, by the techniques mentioned above, from 0.6 mg/l to 60 mg/l (Florent, 1986). For bacteria of the genus Propionibacterium [ Propionibacterium shermanii (ATCC 13673) and freudenreichii (ATCC 6207)], the same production values appear to be described in the literature; e.g. a production of 65 mg/l has been described (European Patent 87,920). However, no screen has yet been described enabling either mutants overproductive of cobalamins or mutants markedly improved in their production of cobalamins to be readily selected or identified.

At the genetic level, little work has been performed to date. The cloning of cob genes (coding for enzymes involved in the biosynthetic process) has been described in Bacillus megaterium (Brey et al., 1986). Eleven complementation groups have been identified by complementation of cob mutants of Bacillus megaterium with plasmids carrying different fragments of Bacillus megaterium DNA. These genes are grouped on the same locus, carried by a 12-kb fragment.

Studies have also been carried out on the cob genes of Salmonella typhimurium . Although the cloning of these has not been described, it has been shown that almost all the genes for cobalamin biosynthesis are grouped together between minutes 40 and 42 of the chromosome (Jeter and Roth, 1987). Only the cysG locus, which must permit the conversion of uro'gen III to precorrin-2, does not form part of this group of genes. However, the activity encoded by this locus and also its biochemical properties have not been described.

In addition, some phenotypes have been associated with cob mutations. In Salmonella typhimurium and in Bacillus megaterium , cob mutants no longer show growth on minimum medium with ethanolamine as a carbon source or as a nitrogen source (Roof and Roth, 1988). This is due to the fact that an enzyme of ethanolamine catabolism, ethanolamine ammonia-lyase (EC 4.3.1.7), has coenzyme B 12 as a cofactor; the cob mutants no longer synthesise coenzyme B 12 , and they can no longer grow with ethanolamine as a carbon source and/or as a nitrogen source. metE mutants of Salmonella typhimurium retain only a methylcobalamin-dependent homocysteine methyltransferase (EC 2.1.1.13). cob mutants of Salmonella typhimurium metE are auxotrophic for methionine (Jeter et al., 1984).

In Pseudomonas denitrificans and Agrobacterium tumefaciens , phenotypes associated with a total deficiency of cobalamin synthesis have not been described to date.

Finally, work on Pseudomosas denitrificans (Cameron et al., 1989) has led to the cloning of DNA fragments carrying cob genes of this bacterium. These are distributed in four complementation groups carried by at least 30 kb of DNA. At least fourteen complementation groups have been identified by heterologous complementation of cob mutants of Agrobacterium tumefaciens and of Pseudomonas putida with DNA fragments of Pseudomonas denitrificans carrying cob genes.

However, hitherto, none of these genes has been purified, and no nucleotide sequence has been described. Similarly, no protein identification nor any catalytic function attributed to the product of these genes has been described. Furthermore, no improvement in production of cobalamins by recombinant DNA techniques could be obtained. The amplification of cob genes of Bacillus megaterium does not bring about, in the strain from which they have been cloned, an improvement in production of cobalamins (Brey et al., 1986). In Salmonella typhimurium , physiological studies have been carried out in order to determine conditions under which a strong transcription of the cob genes studied was observed (Escalante and Roth, 1987). Under these conditions, there is no improvement in the production of cobalamins, although genes of the biosynthetic pathway are more expressed than under standard culture conditions.

The present invention results from the precise identification of DNA sequences coding for polypeptides involved in the biosynthesis of cobalamins and/or cobamides. A subject of the invention hence relates to the DNA sequences coding for the polypeptides involved in the biosynthesis of cobalamines and/or cobamides. More especially, the subject of the invention is the cobA, cobB, cobC, cobD, cobE, cobF, cobG, cobH, cobI, cobJ, cobK, cobL, cobM, cobN, cobO, cobP, cobQ, cobS, cobT, cobU, cobV, cobW, cobX and corA genes, any DNA sequence homologous with these genes resulting from the degeneracy of the genetic code, and also DNA sequences, of any origin (natural, synthetic, recombinant), which hybridise and/or which display significant homologies with these sequences or with fragments of the latter, and which code for polypeptides involved in the biosynthesis of cobalamins and/or cobamides. The subject of the invention is also the genes containing these DNA sequences.

The DNA sequences according to the present invention were isolated from an industrial strain, Pseudomonas denitrificans SC510, derived from strain MB580 (U.S. Pat. No. 3,018,225), by complementation of cob mutants of A. tumefaciens and P. putida ; and of Methanobacterium ivanovii . The clones obtained could be analysed precisely, in particular by mapping using insertions of a derivative of transposon Tn5. These genetic studies have enabled the cob or cor genes to be localised on the restriction map and their sequencing to be carried out. An analysis of the open reading frames then enabled the coding regions of these DNA fragments to be demonstrated.

The subject of the present invention is also the use of these nucleotide sequences for cloning the cob genes of other bacteria. In effect, it is known that, for proteins catalysing the same activities, sequences are conserved, the divergence being the evolutionary divergence (Wein-Hsiung et al., 1985). It is shown in the present invention that there is a significant homology between the nucleotide sequences of different microorganisms coding for polypeptides involved in the biosynthesis of cobalamins and/or cobamides. The differences which are seen result from the evolutionary degeneracy, and from the degeneracy of the genetic code which is linked to the percentage of GC in the genome of the microorganism studied (Wein-Hsiung et al., 1985).

According to the present invention, a probe may be made with one or more DNA sequences of Pseudomonas denitrificans in particular, or with fragments of these, or with similar sequences displaying a specific degree of degeneracy in respect of the use of the codons and the percentage of GC in the DNA of the bacterium which it is desired to study. Under these conditions, it is possible to detect a specific hybridisation signal between the probe and fragments of genomic DNA of the bacterium studied; this specific hybridisation signal corresponds to the hybridisation of the probe with the isofunctional cob genes of the bacterium. The cob genes as well as their products may then be isolated, purified and characterised. The invention thus provides a means enabling access to be gained, by hybridisation, to the nucleotide sequences and the polypeptides involved in the biosynthesis of cobalamins and/or cobamides of any microorganism.

The subject of the present invention is also a recombinant DNA containing at least one DNA sequence coding for a polypeptide involved in the biosynthesis of cobalamins and/or cobamides, and in particular a recombinant DNA in which the said sequence or sequences are placed under the control of expression signals.

In this connection, promoter regions may, in particular be positioned at the 5′ end of the DNA sequence. Such regions may be homologous or heterologous to the DNA sequence. In particular, strong bacterial promoters such as the promoter of the tryptophan operon Ptrp or of the lactose operon Plac of E. coli , the leftward or rightward promoter of bacteriophage lambda, the strong promoters of phages of bacteria such as Corynebacteria, the functional promoters in Gram-negative bacteria such as the Ptac promoter of E. coli , the PxylS promoter of the xylene catabolism genes of the TOL plasmid and the amylase promoter of Bacillus subtilis Pamy may be used. Promoters derived from glycolytic genes of yeasts may also be mentioned, such as the promoters of the genes coding for phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, lactase or enolase, which may be used when the recombinant DNA is to be introduced into a eukaryotic host. A ribosome binding site will also be positioned at the 5′ end of the DNA sequence, and it may be homologous or heterologous, such as the ribosome binding site of the cII gene of bacteriophage lambda.

Signals necessary to transcription termination may be placed at the 3′ end of the DNA sequence.

The recombinant DNA according to the present invention may then be introduced directly into a host cell compatible with the chosen expression signals, or be cloned into a plasmid vector to enable the DNA sequence in question to be introduced in a stable manner into the host cell.

Another subject of the invention relates to the plasmids thereby obtained, containing a DNA sequence coding for a polypeptide involved in the biosynthesis of cobalamins and/or cobamides. More specifically, these plasmids also contain a functional replication system and a selectable marker.

The subject of the invention is also the host cells into which one or more DNA sequences as defined above, or a plasmid as defined hereinbefore, has/have been introduced.

Another subject of the invention relates to a method for production of polypeptides involved in the biosynthesis of cobalamins and/or cobamides. According to this method, a host cell is transformed with a DNA sequence as described above, this transformed cell is cultured under conditions for expression of the said sequence and the polypeptides produced are then recovered.

The host cells which may be used for this purpose are either prokaryotes or eukaryotes, animal cells or plant cells. Preferably, they will be chosen from bacteria, and especially bacteria of the genus E. coli, P. denitrificans, A. tumefaciens or R. meliloti.

Another use of the DNA sequences according to the present invention lies in a method for amplification of the production of cobalamins and/or cobamides, by recombinant DNA techniques. In effect, if the limitation of the metabolic flux of the biosynthesis of cobalamins and/or cobamides is due to a limitation in the activity of an enzyme in the biosynthetic pathway, an increase in this activity by increasing the expression of this same enzyme using recombinant DNA techniques (gene amplification, substitution of the transcription/translation signals with more effective signals, etc.) will lead to an increase in the biosynthesis of cobalamins and/or cobamides. It is also possible that the limitation of the production of cobalamins and/or cobamides results from a biochemical regulation. In this case, the cob gene or genes corresponding to the regulated enzyme may be specifically mutagenised in vitro in order to obtain mutated genes whose products will have lost the regulation mechanisms impeding an improvement in the production.

The method according to the present invention consists in transforming a microorganism productive of cobalamins and/or cobamides, or only potentially productive of these compounds (i.e. deficient in one or more steps of the biosynthesis), with a DNA sequence as defined above, then in culturing this microorganism under conditions for expression of the said sequence and for synthesis of cobalamins and/or cobamides, and lastly in recovering the cobalamins and/or cobamides produced. Such a method is applicable, in particular, to all the productive microorganisms mentioned on pages 5 and 6, and more specifically to microorganisms of the genus P. denitrificans, Rhizobium meliloti , or Agrobacterium tumefaciens . In a preferred embodiment, the microorganism is P. denitrificans , and especially strain SC510. As regards potentially productive microorganisms, the DNA sequences used will be those corresponding to the steps of the biosynthesis which the microorganism cannot carry out.

Using the present invention, and by the various stragegies described above, an improvement in the production of cobalamins and/or cobamides may be obtained for any microorganism productive or potentially productive of cobalamins and/or cobamides. It will suffice to culture this recombinant microorganism under suitable conditions for the production of cobalamins and for the expression of the DNA sequences introduced. This culturing may be carried out batchwise or alternatively in continuous fashion, and the purification of the cobalamins may be carried out by the methods already used industrially (Florent, 1986). These methods comprise, inter alia:

i) solubilisation of the cobalamins and their conversion to their cyano form (e.g. by heat treatment of the fermentation must, with potassium cyanide in the presence of sodium nitrite), then

ii) purification of the cyanocobalamins in various steps which can be, e.g.

a) adsorption on different substrates such as Amberlite IRC-50, Dowex 1×2 or Amberlite XAD-2, followed by an elution with a water/alcohol or water/phenol mixture, then

b) extraction in an organic solvent, and lastly

c) precipitation or crystallisation from the organic phase, either by the addition of reagents or dilution in a suitable solvent, or by evaporation.

The present invention shows, furthermore, that it is possible by recombinant DNA techniques to improve the cobalamin production of a bacterium productive of cobalamins by cumulating improvements. This amounts to obtaining a first improvement as described above, and then in improving this improvement, still using recombinant DNA techniques, i.e., e.g. by amplifying genes for cobalamin biosynthesis.

Another subject of the present invention relates to the polypeptides involved in the biosynthesis of cobalamins and/or cobamides. In particular, the subject of the present invention is all polypeptides, or derivatives or fragments of these polypeptides, which are encoded by the DNA sequences described above, and which are involved in the pathway of biosynthesis of cobalamins and/or cobamides. The amino acid sequence of these polypeptides is described, as well as some of their physicochemical properties. An enzymatic activity or specific properties have also been associated with each of them.

In this connection, the subject of the invention is the polypeptides participating in the conversion of precorrin-3 to cobyrinic acid a,c-diamide, and more especially in the transfer of a methyl group from SAM to positions C-1, C-5, C-11, C-15 and C-17.

The subject of the invention is also the polypeptides:

participating in the conversion of cobyric acid to cobinamide, or

possessing an S-adenosyl-L-methionine:precorrin-2 methyltransferase (SP2MT) activity, or

possessing a cobyrinic and/or hydrogenobyrinic acid a,c-diamide synthase activity, or

possessing a precorrin-8x mutase activity, or

possessing a nicotinate-nucleotide: dimethylbenzimidazole phosphoribosyltransferase activity, or

possessing a cobalamin-5′-phosphate synthase activity, or

possessing a cobyric acid synthase activity, or

possessing a cob(I)alamin adenosyl-transferase activity, or

possessing a precorrin-6x reductase activity, or

participating in the conversion of hydrogenobyrinic acid a,c-diamide to cobyrinic acid a,c-diamide.

Advantageously, the subject of the invention is a polypeptide chosen from the COBA, COBB, COBC, COBD, COBE, COBF, COBG, COBH, COBI, COBJ, COBK, COBL, COBM, COBN, COBO, COBP, COBQ, COBS, COBT, COBU, COBV, COBW, COBX and CORA proteins presented in FIGS. 15, 16 , 40 , 41 and 47 .

Furthermore, the use of the hybridisation probes described above makes it possible, from genes isolated in other microorganisms, to characterise and isolate the isofunctional polypeptides of other microorganisms. In this manner, the present invention shows that the sequence of a COB protein of Pseudomonas denitrificans is significantly homologous with the protein sequences of other microorganisms displaying the same type of activity. Between these COB proteins catalysing the same reaction in different microorganisms, only the evolutionary distances have introduced variations (Wein-Hsiung et al., 1985). The subject of the present invention is also these isofunctional polypeptides.

The assignment of a particular enzymatic activity is the result of an analysis which may be performed according to various strategies. In particular, in vitro affinity studies with respect to SAM (S-adenosyl-L-methionine) make it possible to assign a methyl transferase activity to a protein capable of binding SAM, and hence to assign its involvement in one of the steps of transfer of methyl groups which occur between uro'gen III and cobyrinic acid. Another means of assessing the activity of these polypeptides consists in assaying the intermediates in the pathway of biosynthesis of cobalamins which are accumulated in mutants incapable of expressing these polypeptides (identified by complementation experiments). These analyses enable it to be deduced that the polypeptide in question has the accumulated intermediate as its substrate, thereby enabling its activity in the biosynthetic pathway to be situated and defined. The present invention also describes a method for assaying the enzymatic activities of the biosynthetic pathway, applicable to any strain productive of cobalamins and/or cobamides. These assays enable the enzymatic activity assayed to be purified from any strain productive of these compounds. From this purified activity, the NH 2 -terminal sequence of the COB protein in question, or alternatively that of the subunits of this protein, may be determined, thereby enabling the structural gene or genes which code for the activity in question to be identified. For Pseudomonas denitrificans , the structural genes which code for activities of the biosynthetic pathway are identified by finding, for each NH 2 -terminal sequence, the COB protein having the same NH 2 -terminal sequence.

The present invention also describes a method enabling intermediates in the pathway of biosynthesis of cobalamins or of other corrinoids to be identified and assayed in strains productive of cobalamins. These intermediates may be assayed both in culture musts and in the cells themselves. The intermediates which may be assayed are all the corrinoids which occur in the biosynthetic pathway after cobyrinic acid, namely, apart from cobyrinic acid, cobyrinic acid monoamide, cobyrinic acid diamide, cobyrinic acid triamide, cobyrinic acid tetraamide, cobyrinic acid pentaamide, cobyric acid, cobinamide, cobinamide phosphate, GDP-cobinamide, coenzyme B 12 phosphate and coenzyme B 12 . The non-adenosylated forms of these products may also be assayed by this technique.

Other subjects and advantages of the present invention will become apparent on reading the examples and the drawings which follow, which are to be considered as illustrative and not limiting.

Definition of the Terms Employed and Abbreviations.

FIG. 1 : Structure of coenzyme B 12 ; the 5′-deoxyadenosyl group is replaced by a CH 3 group for methylcobalamin, by a cyano group for cyanocobalamin, by a hydroxyl group for hydroxocobalamin.

FIG. 2 : Biosynthesis of cobalamins and various steps of this biosynthesis. X: axial ligands of the cobalt; the ligand at a may be different from the ligand at b. R: ligand at a of the cobalt which defines the cobalamin type (see FIG. 1 ).

FIG. 3 : Structures of uro'gen III, precorrin-1, precorrin-2 and precorrin-3.

FIG. 4 : Structural formulae of uro'gen III and cobyrinic acid. Between uro'gen III and cobyrinic acid, there occur 8 SAM-dependent methyl transfers successively at C-2, C-7, C-20, C-17, C-12, C-1, C-15 and C-5, a decarboxylation at C-12, elimination of the carbon at C-20 and insertion of the cobalt atom. X: axial ligands of the cobalt; the ligand at a may be different from the ligand at b.

FIG. 5 : Final steps of the biosynthesis of cobalamins.

In order to clarify the diagram, details of the corrin ring-system have been omitted. The five enzymatic steps are represented: 1, cobinamide kinase; 2, cobinamidephosphate guanylyltransferase; 3, cobalamin-5′-phosphate synthase; 4, cobalamin-5′-phosphate phosphohydrolase; 5, nicotinatenucleotide:DMBI phosphoribosyltransferase.

FIGS. 6 A- 6 D: Restriction maps of the 5.4-kb ClaI-HindIII-HindIII-HindIII, 8.7-kb EcoRI, 4748-bp SalI-SalI-SalI-SalI-SalI-BglI and 3855-bp SstI-SstI-BamHI fragments. Only the 20 restriction enzymes which cut the DNA least frequently are shown. The cleavage sites of each enzyme are indicated by a vertical line.

FIGS. 7 A- 7 I: Nucleotide sequence of both strands of the 5378-bp ClaI-HindIII-HindIII-HindIII fragment of Pseudomonas denitrificans (SEQ ID NO: 1). The strand situated at the top is to be read from 5′ to 3′ in the left-to-right direction which corresponds to the left-to-right orientation of the sequenced fragment presented in FIG. 6 . The ClaI site occurs at position 23 (beginning of the cleavage site) since, in this sequence, there occur PstI, SalI and XbaI restriction sites which have appeared during clonings in multisites with a view to sequencing. The sequence of the ClaI-HindIII-HindIII-HindIII fragment hence begins at position 23.

FIG. 8 : Nucleotide sequence of both strands of the 8753-bp EcoRI fragment of Pseudomonas denitrificans SEQ ID NO: 2. The strand situated at the top is to be read from 5′ to 3′ in the left-to-right direction which corresponds to the left-to-right orientation of the fragment of the restriction map presented in FIG. 6 .

FIGS. 9 A- 9 E: Analysis of the probabilities of the coding frames on the basis of codon preference using the programme of Staden and MacLachlan (1982) on the 6 reading frames of the 5378-bp ClaI-HindIII-HindIII-HindIII fragment. For the frames belonging to the same coding strand, the most probable frame corresponds to that in which a dotted line, not interrupted by stop codons, is placed under the probability line for this frame.

A. Sequence extending from nucleotide 1 to nucleotide 1200. By means of this analysis, open reading frame 1 is identified. It begins at the ATG at position 549 and ends at the TGA at position 1011.

B. Sequence extending from nucleotide 1000 to nucleotide 2200. By means of this analysis, open reading frame 2 is identified. It begins at the ATG at position 1141 and ends at the TGA at position 1981.

C. Sequence extending from nucleotide 1800 to nucleotide 3400. By means of this analysis, open reading frame 3 is identified. It begins at the ATG at position 1980 and ends at the TGA at position 3282.

D. Sequence extending from nucleotide 3000 to nucleotide 4500. By means of this analysis, open reading frame 4 is identified. It begins at the ATG at position 3281 and ends at the TGA at position 4280.

E. Sequence extending from nucleotide 3800 to nucleotide 5378. By means of this analysis, open reading frame 5 is identified. It begins at the GTG at position 4284 and ends at the TGA at position 5253.

FIGS. 10 A- 10 H: Analysis of the probabilities of the coding frames on the basis of codon preference using the programme of Staden and MacLachlan (1982) on the 6 reading frames of the 8753-bp EcoRI fragment. For the frames belonging to the same coding strand, the most probable frame corresponds to that in which a dotted line, not interrupted by stop codons, is placed under the probability line for this frame.

A. Sequence extending from nucleotide 650 to nucleotide 1650. By means of this analysis, open reading frame 6 is identified. It begins at the ATG at position 736 and ends at the TGA at position 1519.

B. Sequence extending from nucleotide 1400 to nucleotide 3100. By means of this analysis, open reading frame 7 is identified. It begins at the ATG at position 1620 and ends at the TAG at position 2997.

C. Sequence extending from nucleotide 2700 to nucleotide 3700. By means of this analysis, open reading frame 8 is identified. It begins at the ATG at position 3002 and ends at the TGA at position 3632.

D. Sequence extending from nucleotide 3500 to nucleotide 4100. By means of this analysis, open reading frame 9 is identified. It begins at the GTG at position 3631 and ends at the TGA at position 4366.

E. Sequence extending from nucleotide 4150 to nucleotide 5150. By means of this analysis, open reading frame 10 is identified. It begins at the ATG at position 4365 and ends at the TGA at position 5127.

F. Sequence extending from nucleotide 5000 to nucleotide 6000. By means of this analysis, open reading frame 11 is identified. It begins at the ATG at position 5893 and ends at the TAG at position 5110.

G. Sequence extending from nucleotide 5700 to nucleotide 7200. By means of this analysis, frame 12 is identified. It begins at the ATG at position 5862 and ends at the TAA at position 7101.

H. Sequence extending from nucleotide 7000 to nucleotide 8000. By means of this analysis, open reading frame 13 is identified. It begins at the ATG at position 7172 and ends at the TTG at position 7931.

FIG. 11 : Construction of plasmids pXL556, pXL545 and pXL723.

A 2.4-kb ClaI-EcoRV fragment containing the cobA and cobE genes is excised from the 5.4-kb fragment and then purified. An EcoRI linker is added at the EcoRV site and the fragment is then inserted into pXL59 between the ClaI-EcoRI sites. The plasmid thereby constructed is designated pXL556.

The construction is comparable for pXL545: a 1.9-kb ClaI-HindIII-HindIII fragment is excised from the 5.4-kb fragment and then purified. This fragment contains only the CobE gene. An EcoRI linker is added at the HindIII site and the fragment is then inserted into pXL59 between the ClaI-EcoRI sites. pXL723 is constructed as follows: a 2.3-kb EcoRI-HindIII fragment is excised from the 5.4-kb fragment and purified, and the ends are then filled in with the large fragment of E. coli DNA polymerase I. This fragment is cloned into pRK290 (Ditta et al., 1981) digested with EcoRI and then treated with the large fragment of E. coli DNA polymerase I in order to fill in the ends.

The restriction sites which are shown in brackets correspond to sites which have disappeared after treatment with the large fragment of E. coli DNA polymerase I. 1, PstI-SstI fragment of RSF1010 (De Graff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); 3, BamHI-SstI fragment containing the lactose operon of E. coli without its promoter, the operator, the translation initiation site and the first 8 non-essential codons of lacZ (Casadaban et al., 1983); 4, Sau3AI fragment of Pseudomonas putida KT2440 (Bagdasarian et al., 1981); ori, origin of replication; nic, relaxation site; mob, locus essential for mobilisation; Km r , kanamycin resistance gene (Bagdasarian et al., 1981); B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SalI; X, XhoI; Xb, XbaI.

FIG. 12 : Studies of the insertions of transposons Tn5Sp r and Tn5 into the 5378-bp fragment. The insertions of transposon Tn5 into plasmid pXL723 are shown as in FIG. 14; those of transposon Tn5Sp r , into the chromosome of strain G2 Rif r , are boxed; the insertions into the chromosome of SC510 Rif r of cassettes carrying the kanamycin resistance gene (1630 and 1631) are shown with an arrow, according to the orientation of transcription of the kanamycin resistance gene, under the insertion number. The open reading frames deduced from the sequence are given in this figure (from cobA to cobE); + or − signs are shown under each insertion of transposon or of resistance cassette to indicate that the insertion is inactivating (−) or otherwise (+), i.e. for the complementation of different mutants (the case with the insertions of transposons Tn5), or that the insertion abolishes the cobalamin production of the strain in which it takes place. There is an absence of complementation when the recombinant mutant synthesises less than threefold less cobalamins than the level of synthesis of the strain from which the mutant is derived. The inserts of plasmids pXL545, pXL1500, pXL1397 and pXL302 are shown with the restriction sites occurring at their ends. These inserts are cloned into broad host range plasmids, pXL435 and pXL59 (Cameron et al., 1989):

plasmid pXL545 corresponds to plasmid pXL545 described in FIG. 11 with, in addition, the 2-kb BamHI fragment of pHP45 (Prentki and Krisch) containing a spectinomycin resistance gene cloned at the BamHI site of pXL545;

plasmid pXL1500 corresponds to the 4.2-kb BglII-SstI fragment presented in this figure, cloned at the BamHI and SstI sites of pKT230 (Bagdasarian et al., 1981); presented in FIG. 30;

plasmid pXL1397 corresponds to the 2.4-kb HindIII-SstI fragment indicated in the figure, inserted between the HindIII and SstI sites of the multisite of pXL435 (Cameron et al., 1989) described in FIG. 30; plasmid pXL302 corresponds to the 2.3-kb EcoRI-HindIII fragment as described in the figure, inserted between the EcoRI and HindIII sites of pXL59 (Cameron et al., 1989) described in FIG. 30, the HindIII site used being the site occurring in the cloning multisite of pXL59;

pXL723 is described in FIG. 11, like pXL545.

+ or − signs are shown above each of these inserts to indicate whether there is complementation by the plasmid in question of the chromosomal insertions shown underneath. C, ClaI; E, EcoRI; H, HindIII; RV, EcoRV; Sau, Sau3AI; S, SstI.

FIG. 13 : Construction of plasmids pXL253 and pXL367.

The 8.7-kb EcoRI fragment is excised and then purified from plasmid pXL151. It is cloned at the EcoRI site of pKT230 to give pXL253. This same fragment is inserted at the EcoRI site of pRK290 (Ditta et al., 1981) to give pXL367. 1, PstI-SstI fragment of RSF1010 (De Graff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); ori, origin of replication; nic, relaxation site; mob, locus essential for mobilisation (Bagdasarian et al., 1981); B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SalI; X, XhoI; Xb, XbaI; tet r , tetracycline resistance gene; Km r , kanamycin resistance gene.

FIG. 14 : Studies of the insertions of transposons Tn3lacZ and Tn5 into the 8.7-kb EcoRI fragment cloned into pRK290 (Ditta et al., 1980). The insertions of transposons Tn3lacZ are underlined, in contrast to those of transposons Tn5. The open reading frames deduced from the sequence (cobF to cobM) are given in this figure, and the eight groups of inactivating insertions (numbered from 1 to 8) are presented; + or − signs are shown under each transposon insertion to indicate that the insertion is inactivating (−) or otherwise (+) for the complementation of different mutants. There is an absence of complementation when the recombinant mutant synthesises less than threefold less cobalamins than the level of synthesis of the strain from which the mutant is derived. These groups of inactivating insertions correspond to the following mutants: 1, G615; 2, G614 and G616; 3, G613 and G614; 4, G620; 5, G638; 6, G610 and G609; 7, G612; 8, G611. These mutants are Cob mutants of Agrobacterium tumefaciens already described (Cameron et al., 1989). A restriction map of the 8.7-kb fragment is given at the bottom of the figure.

FIGS. 15 A- 15 K: The coding sequences of each of the genes of the 5.4-kb fragment, cobA to cobE, respectively, are indicated. The sequences of the proteins COBA to COBE encoded by these sequences appear under their respective coding sequence, cobA to cobE. The amino acid composition of each protein, in number and in percentage, respectively, of COBA to COBE, is presented, as well as the molecular weight, the index of polarity, the isoelectric point and the optical density at 260 nm and 280 nm of a solution containing 1 mg/ml of purified protein. The hydrophilicity profile of each COBA to COBE protein, respectively, is shown; it was calculated on the basis of the programme of Hopp and Woods (1981). Positive values correspond to regions of the protein which are hydrophilic. The position of the amino acids is indicated as abscissa, while the value of the index of hydrophilicity is shown as ordinate; when this value is positive, this indicates that the region of the protein is hydrophilic.

FIGS. 16 A- 16 R: The coding sequences of each of the genes of the 8.7-kb fragment, cobF to cobM respectively, are indicated. The sequences of the COBF to COBM proteins encoded by these sequences appear under their sequence. The legend is identical to that for FIG. 15 . NB. We have shown the COBF protein as beginning at the ATG located at position 736; it is possible that the ATG located at position 751 is the true initiation codon of this protein.

FIG. 17 : Reaction catalysed by cobyrinic acid a,c-diamide synthase. CADAS catalyses the amidation of the carboxylic acid functions of the peripheral acetate chains a and c of cobyrihic acid to give cobyrinic acid diamide; the donor of the amine group used in the enzymatic test is L-glutamine; it gives L-glutamic acid on deamination. X corresponds to the axial ligands of the cobalt, which may be different from one another.

FIG. 18 : Reaction catalysed by SP 2 MT. SP 2 MT catalyses the transfer of a methyl from SAM to dihydrosirohydrochlorin or precorrin-2 to give precorrin-3. The methyl group is transferred to position C-20 of the porphyrin ring-system.

FIG. 19 : Structure of hydrogenobyrinic acid and of hydrogenobyrinic acid a,c-diamide.

FIG. 20 : Affinities of the COBA and COBF proteins for SAM. The curves give in arbitrary units the radioactivity at emergence from the TSK-125 column for each protein applied to this column. The retention times are indicated in minutes and the radioactivity peak corresponding to free SAM is observed at the time of 10 min 30 sec.

FIG. 21 : Comparison of the sequences of COBA and COBI.

Only the regions 1, 2 and 3, of strong homology, are presented. = signs are placed between identical residues and − signs between homologous residues (H K R, LIVM, A G S T, Y F W, D E Q N B Z, P, C).

FIG. 22 : Comparison of the primary sequences of the proteins COBA of Pseudomonas denitrificans and CYSG of E. coli . The alignment has been done according to the programme of Kanehisa, 1984. = signs are placed between identical residues and − signs between homologous residues (HKR, LIVM, A G S T, Y F W, D E Q N B Z, P, C). The regions 1, 2 and 3 correspond to zones of strong homology between the proteins.

FIG. 23 : Comparison of the sequences of CYSG of E. coli with COB proteins of Pseudomonas denitrificans (COBA, COBF, COBI, COBJ, COBL and COBM). The comparisons concern the regions 1, 2 and 3, of strong homologies, which exist between CYSG, COBA and COBI. The positions in the protein sequences of the regions displaying homologies are presented in the figure. We have considered the following groups of homologous residues: H K R, L I V M, A G S T, Y F W, D E Q N B Z, P, C. If there are at least 3 homologous residues at the same position, we have boxed these amino acids.

FIG. 24 : Construction of plasmids pXL1148 and pXL1149.

pXL1148 is constructed as follows: the 1.9-kb BamHI-BamHI-SstI-SstI fragment of the 8.7-kb fragment containing the cobH and cobI genes is purified, and XbaI and EcoRI linkers are placed at the BamHI and SstI ends respectively. This fragment is then inserted. between the XbaI and EcoRI sites of the broad host range plasmid pXL59 (Cameron et al., 1989) to give plasmid pXL1148.

pXL1149 is constructed like pXL1148, apart from the fact that the fragment initially purified is the 1.5-kb BamHI-BamHI-SstI fragment instead of the fragment additionally containing the small 400-bp SstI fragment used for pXL1148. The fragment then undergoes the same enzymatic treatments and the same cloning into pXL59.

1, PstI-SstI fragment of RSF1010 (De Graff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); 3, BamHI-SstI fragment containing the lactose operon of E. coli without promoter, operator, translation initiation site and the first 8 non-essential codons of lacZ (Casadaban et al., 1983); 4, Sau3AI fragment of Pseudomonas putida KT2440 (Bagdasarian et al., 1981); ori, origin of replication; nic, relaxation site; Km r , kanamycin resistance gene; mob, locus essential for mobilisation (Bagdasarian et al., 1981); B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SalI; X, XhoI; Xb, XbaI.

FIG. 25 : Total proteins of strains SC510 Rif r , SC510 Rif r pKT230, SC510 Rif r pXL1148, SC510 Rif r pXL1149 analysed in 10% SDS-PAGE as described. The bacteria were cultured for 4 days in PS4 medium, and lysates of the total proteins were then made. Lane 1, SC510 Rif r ; lane 2, SC510 Rif r pXL1149; lane 3, SC510 Rif r pXL1148; lane 4, SC510 Rif r pKT230. The molecular masses of the molecular mass markers are indicated. The positions to which the COBI and COBH proteins migrate are indicated.

FIG. 26 : Construction of plasmids pXL1496 and pXL1546.

Plasmid pXL1496 enables the COBF protein to be overexpressed in E. coli , and plasmid pXL1546 enables COBF to be overexpressed in Pseudomonas denitrificans.

The 2.2-kb EcoRI-XhoI fragment is excised and purified from the 8.7-kb fragment. It is cloned at the EcoRI site of phage M13mp19 to give plasmid pXL1405. An NdeI site is then introduced by directed mutagenesis, as described above, at position 733 of this fragment; in this manner, an NdeI site occurs exactly on the presumed initiation codon of the cobF gene. The new plasmid thereby obtained is designated pXL1406. A 1.5-kb NdeI-SphI-SphI fragment, containing the cobF gene starting from its presumed initiation codon, is purified after partial digestion with the appropriate enzymes and ligated with the appropriate fragments of plasmid pXL694 (120-bp EcoRI-NdeI fragment containing expression signals of E. coli —see text—and 3.1-kb EcoRI-SphI fragment containing the ampicillin resistance gene, the replication functions of the plasmid and also the terminators of the rrnB operon of E. coli , as described in the text). The plasmid thereby constructed is designated pXL1496.

pXL1546 is constructed as follows: the 2-kb EcoRI-BamHI-BamHI fragment of pXL1496 is purified by partial digestion with the appropriate enzymes; this fragment contains the expression signals of E. coli , followed by the cobF gene and then the 5′ portion of the cobG gene, this portion itself being followed by terminators of the rrnB operon of E. coli , as described in the text. This fragment is cloned into the multihost plasmid pKT230 (Bagdasarian et al., 1981) described in FIG. 30. B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI, Sa, SalI; X, XhoI; Xb, XbaI; Kmr, kanamycin resistance gene; Amp, ampicillin resistance gene.

FIG. 27 : Total proteins of strains SC510 Rif r , SC510 Rif r pKT230, SC510 Rif r pXL1546 analysed in 10% SDS-PAGE as described. The bacteria were cultured for 4 days in PS4 medium, and lysates of the total proteins were then made. Lane 1, SC510 Rif r ; lane 2, SC510 Rif r pKT230; lane 3, SC510 Rif r pXL1546. The molecular masses of the molecular mass markers are indicated. The position to which the COBF protein migrates is indicated.

FIG. 28 : Total proteins of the strains E. coli B and E. coli B pXL1496 analysed in 10% SDS-PAGE as described. Lane 1 , E. coli pXL1496 cultured in the absence of tryptophan; lane 2 , E. coli pXL1496 cultured under the same conditions in the presence of tryptophan; lane 3 , E. coli cultured in the absence of tryptophan; lane 4 , E. coli cultured under the same conditions in the presence of tryptophan. The molecular masses of the markers are indicated. The position of migration of the COBF protein is indicated.

FIG. 29 : Construction of plasmids pXL525 and pXL368.

Plasmid pXL368 is constructed as follows: the 2.4-kb EcoRV-ClaI fragment (containing the cobA and cobE genes) is purified from plasmid pXL556, thereby enabling this fragment to be obtained with a BamHI site and an XbaI site at the ends; this fragment is cloned into pXL203 at the BamHI and XbaI sites.

For the construction of pXL525, an XbaI linker is added at the EcoRI site situated at the right-hand end of the 8.7-kb EcoRI fragment; this 8.7-kb EcoRI-XbaI fragment is then cocloned with the 2.4-kb EcoRI-XbaI fragment originating from pXL556 and containing cobA and cobE.

The restriction sites which are shown in brackets correspond to sites which have disappeared after treatment with the large fragment of E. coli DNA polymerase I. 1, PstI-SstI fragment of RSF1010 (De Graff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); ori, origin of replication; nic, relaxation site; mob, locus essential for mobilisation; Km r , kanamycin resistance gene (Bagdasarian et al., 1981); B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SalI; X, XhoI; Xb, XbaI; tet, tetracycline resistance gene; Amp r and Amp, ampicillin resistance gene.

FIG. 30 : Plasmids of the incompatibility group Q having a broad host range in Gram-negative bacteria. These plasmids are described in a previous publication (Cameron et al., 1989) and are used in the present invention.

1, PstI-SstI fragment of RSF1010 (De Graff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); 3, BamHI-SstI fragment containing the lactose operon of E. coli without promoter, operator, translation initiation site and the first 8 non-essential codons of lacZ (Casadaban et al., 1983); 4, Sau3AI fragment of Pseudomonas putida KT2440 (Bagdasarian et al., 1981); ori, origin of replication; nic, relaxation site; Km r , kanamycin resistance gene; Sm r , streptomycin resistance gene; mob, locus essential for mobilisation (Bagdasarian et al., 1981); B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SAI; X, XhoI; Xb, XbaI.

FIG. 31 : Retention time of different corrinoid standards (1 mg/standard) on the separation system described in Example 7. The column used is a Nucleosil C-18 column (Macherey-Nagel). Against each absorbance peak, a number is shown corresponding to the corrinoid described below. The retention time is shown as abscissa and the absorbance at 371 nm appears as ordinate.

1, cobyrinic acid; 2, cobyrinic acid a-amide; 3, cobyrinic acid g-amide; 4, cobyrinic acid a,g-diamide; 5, cobyrinic acid c-amide; 6, cobyrinic acid c,g-diamide; 7, cobyrinic acid a,c-diamide; 8, cobyrinic acid triamide; 9, cobyrinic acid tetraamide; 10, cobyrinic acid pentaamide; 11, cobyric acid; 12, GDP-cobinamide; 13, cobinamide phosphate; 14, cobinamide; 15, cyanocobalamin 5′-phosphate; 16, cyanocobalamin.

FIGS. 32 A- 32 H: Nucleotide sequence of both strands of the 4748-bp SalI-SalI-SalI-SalI-SalI-BglI fragment of Pseudomonas denitrificans (SEQ ID NO: 29). The strand situated at the top is to be read from 5′ to 3′ in the left-to-right direction which corresponds to the left-to-right orientation of the fragment of the restriction map presented in FIG. 6 .

FIGS. 33 A- 33 G: Nucleotide sequence of both strands of the 3855-bp SstI-SstI-BamHI fragment of Pseudomonas denitrificans (SEQ ID NO: 30). The strand situated at the top is to be read from 5′ to 3′ in the left-to-right direction which corresponds to the left-to-right orientation of the fragment of the restriction map presented in FIG. 6 .

FIGS. 34 A- 34 D: Analysis of the probabilities of the coding frames on the basis of codon preference using the programme of Staden and MacLachlan (1982) on the six reading frames of the 4748-bp SalI-SalI-SalI-SalI-SalI-BglI fragment. For the frames belonging to the same coding strand, the most probable frame corresponds to that in which a dotted line, not interrupted by stop codons, is placed under the probability line for this frame. 4a. Analysis of the sequence corresponding to nucleotides 200 to 800. This analysis enables open reading frame 14 to be identified. It begins at the ATG at position 660 and ends at the TGA at position 379. 4b. Analysis of the sequence corresponding to nucleotides 800 to 1500. This analysis enables open reading frame 15 to be identified. It begins at the GTG at position 925 and ends at the TAA at position 1440. 4c. Analysis of the sequence corresponding to nucleotides 1450 to 2600. This analysis enables open reading frame 16 to be identified. It begins at the ATG at position 1512 and ends at the TGA at position 2510. 4d. Analysis of the sequence corresponding to nucleotides 2500 to 4650. This analysis enables open reading frame 17 to be identified. It begins at the GTG at position 2616 and ends at the TGA at position 4511.

FIGS. 35 A- 35 D: Analysis of the probabilities of the coding frames on the basis of codon preference using the programme of Staden and MacLachlan (1982) on the six reading frames of the 3855-bp SstI-SstI-BamHI fragment. For the frames belonging to the same coding strand, the most probable frame corresponds to that in which a dotted line, not interrupted by stop codons, is placed under the probability line for this frame. 5a. Analysis of the sequence corresponding to nucleotides 1 to 905. This analysis enables open reading frame 18 to be identified. It begins at the ATG at position 809 and ends at the TGA at position 108. 5b. Analysis of the sequence corresponding to nucleotides 955 to 2105. This analysis enables open reading frame 19 to be identified. It begins at the ATG at position 1971 and ends at the TGA at position 1063. 5c. Analysis of the sequence corresponding to nucleotides 2000 to 3300. This analysis enables open reading frame 20 to be identified. It begins at the ATG at position 2099 and ends at the TAG at position 3115. 5d. Analysis of the sequence corresponding to nucleotides 3250 to 3855. This analysis enables open reading frame 21 to be identified. It begins at the ATG at position 3344 and ends at the TGA at position 3757.

FIG. 36 : Construction of plasmids pXL233, pXL843 and pXL1558 from pXL154.

The plasmids are constructed in the following manner. The 3.5-kb EcoRI fragment containing the truncated cobS gene and the sequence upstream is excised from pXL154, then purified and cloned to the EcoRI site of pKT230. The plasmid thereby constructed is designated pXL233. The 3.5-kb EcoRI-XhoI-XhoI fragment containing the cobT gene and the sequence downstream is excised and purified from pXL154 by partial digestions. The 4.3-kb EcoRI-EcoRI-EcoRI fragment containing the cobS gene and the sequence upstream is excised and purified from pXL154 and then ligated to the above 3.5-kb fragment. The approximately 8-kb EcoRI-XhoI fragment thereby attained is cloned into the EcoRI and SalI sites of pXL59 to generate plasmid pXL843. Plasmid pXL1558 is constructed in the following manner: the 12-kb HindIII-HindIII fragment is excised from pXL154 and purified, and the ends are then filled in with the large fragment of E. coli DNA polymerase I. This insert is cloned in PRK290 (Ditta et al., 1981) digested with EcoRI and then treated with the large fragment of E. coli DNA polymerase I in order to make the ends blunt. Restriction sites which are shown in brackets correspond to sites which have disappeared during cloning. 1, PstI-SstI fragment of RSF1010 (Degraff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); B, BamHI; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SalI; X, XhoI; Xb, XbaI;

Tet tetracycline resistance gene; Km r , kanamycin resistance gene; Sm r , streptomycin resistance gene.

FIG. 37 : Study of the insertions of the transposon Tn5Sp into the 12-kb HindIII-HindIII insert of pXL154.

The insertions of the transposon are mapped on the 12-kb HindIII-HindIII insert cloned into pXL1558. The chromosomal insertions into strain SC510 Rif r are boxed, that which is not is introduced into strain SBL27 Rif r . A plus or minus sign is shown under each insertion to indicate the Cob phenotype of the strain having this insertion. Absence of complementation (or complementation) of strain G2035 by plasmids pXL1558::Tn5Sp is indicated by minus (or plus) signs below each insertion. The inserts of the plasmids described in

FIG. 36 are shown. The plus (or minus) signs over these plasmids, and aligned with the transposon insertions, show diagrammatically the complementation (or absence) of the transposon-mutated strain by the plasmid. The open reading frames deduced from the sequence are also given in this figure (ORF14 to 17, as well as the corresponding cob genes (cobS and cobT)). E: EcoRI; H: HindIII; X: XhoI.

FIG. 38 : Construction of plasmids pXL1286, pXL1303, pXL1324, pXL1490B and pXL1557 from pXL519. The position of the sequenced fragment appears in the upper part of the figure above the restriction map of the cluster; it is a 3.9-kb SstI-SstI-SstI-BamHI fragment. The plasmids are constructed in the following manner. The 2-kb BglII-EcoRI fragment containing the cobU gene and the sequence downstream is excised from pXL519, then purified and cloned at the BamHI and EcoRI sites of pKT230 to generate plasmid pXL1286. The 2.7-kb SstI-EcoRI fragment containing the truncated cobV gene, cobU gene and the sequence downstream is excised on pXL519, then purified and cloned at the SstI and EcoRI sites of pKT230 to generate plasmid pxL1324. The 1.6-kb SstI-SstI fragment containing the truncated cobV gene and the sequence upstream is excised from pXL519, then purified and cloned at the SstI site of pKT230 to generate plasmid pXL1303. The 3.85-kb SstI-SstI-BamHI fragment is purified after total digestion of pXL519 with BamHI and partial digestion with SstI. This fragment is then cloned at the BamHI and SstI sites of pKT230 to generate pXL1490B. Plasmid pXL1557 is constructed in the following manner: the 9-kb HindIII-BamHI fragment is excised from pXL519 and purified, and the ends are then filled in with the large fragment of E. coli DNA polymerase I. This insert is cloned into pRK290 (Ditta et al., 1981) digested with EcoRI and then treated with the large fragment of E. coli DNA polymerase I to make the ends blunt. The restriction sites which are shown in brackets correspond to sites which have disappeared during cloning. 1, PstI-SstI fragment of RSF1010 (Degraff et al., 1978); 2, PstI-BamHI fragment of pACYC177 (Bagdasarian et al., 1981); B, BamHI;Bg, BglII; C, ClaI; E, EcoRI; H, HindIII; P, PstI; S, SstI; Sa, SalI; X, XhoI; Xb, XbaI; Tet r , tetracycline resistance gene; Kmr kanamycin resistance gene; Sm r , streptomycin resistance gene.

FIG. 39 : Study of the insertions of the transposon Tn5Sp into the 9-kb HindIII-BamHI insert of pXL519. The insertions of the transposon are mapped on the 9-kb HindIII-BamHI insert cloned into pXL1557. The chromosomal insertions into strain SC510 Rif r are boxed, those which are not are introduced into strain SBL27 Rif r . A plus or minus sign is shown under each insertion to indicate the Cob phenotype of the strain having this insertion. Absence of complementation (or complementation) of strain G2040 by plasmids pXL1557::Tn5Sp is indicated by minus (or plus) signs below each insertion. The inserts of the plasmids described in FIG. 6 are shown. The plus (or minus) signs over these plasmids and aligned with the transposon insertions, show diagrammatically the complementation (or absence) of the transposon-mutated strain by the plasmid. The open reading frames deduced from the sequence are also given in this figure (ORF18 to 21), as well as the corresponding cob genes (cobU and cobV).

FIGS. 40 A- 40 G: Coding sequences of each of the genes of the 4.8-kb fragment, cobX, cobS and cobT, respectively, are indicated. The sequence of the COBX, COBS and COBT proteins encoded by these sequences appears under the respective coding sequences cobX, cobS and cobT. The legend is identical to that for FIG. 15 .

FIGS. 41 A- 41 D: Coding sequences of each of the genes of the 3.9-kb fragment, cobU and cobV, respectively, are indicated. The sequence of the COBU and COBV proteins encoded by these sequences appears under the respective coding sequences cobU and cobV. The legend is identical to that of FIG. 15 .

FIG. 42 : A. Total proteins of the strains E. coli BL21 pLysS pET3b and E. coli BL21 pLysS pXL1937 analysed in 10% SDS-PAGE. Lane 1, BL21 pLyspET3b; lane 2 , E. coli BL21 pLysS pXL1937. B. Total proteins of the strains E. coli BL21 , E. coli BL21 pXL1874 and E. coli BL21 pXL1875 analysed in 10% SDS-PAGE. Lane 1 , E. coli BL21; lane 2 , E. coli BL21 pXL1874; lane 3 , E. coli BL21 pXL1875.

The molecular masses of the markers are indicated. The band corresponding to the overexpressed protein is indicated by an arrow.

FIGS. 43 A- 43 V: Nucleotide sequence of both strands of the 13144-bp SstI-SstI-SstI-SstI-BglII-BglII fragment of Pseudomonas denitrificans (SEQ ID NO: 41). The strand situated at the top is to be read from 5′ to 3′ in left-to-right direction which corresponds to the left-to-right orientation of the fragment of the restriction map presented in FIG. 46 .

FIGS. 44 A- 44 G: Restriction map of the 13144-bp SstI-SstI-SstI-SstI-BglII-SstI-BglII fragment of Pseudomonas denitrificans . The position or positions of restriction sites occurring are indicated in increasing order of the cut number on the fragment sequenced; the positions correspond to the sequence presented in FIG. 43 .

FIGS. 45 A- 45 E: Analysis of the probabilities of the coding frames on the basis of codon preference using the programme of Staden and MacLachlan (1982) on the six reading frames of the 13144-bp SstI-SstI-SstI-SstI-BglII-SstI-BglII fragment of Pseudomonas denitrificans . For the frames belonging to the same coding strand, the most probable frame corresponds to that in which a dotted line, not interrupted by stop codons, is placed under the probability line for this frame.

A. Sequence corresponding to nucleotides 1 to 2266. This analysis enables open reading frame 22 to be identified. It begins at the ATG at position 429 and ends at the TAG at position 1884.

Sequence corresponding to nucleotides 2266 to 4000. This analysis enables open reading frame 23 to be identified. It begins at the ATG at position 3364 and ends at the TGA at position 3886.

B. Sequence corresponding to nucleotides 3800 to 5000. This analysis enables open reading frame 24 to be identified. It begins at the ATG at position 3892 and ends at the TAG at position 4954.

C. Sequence corresponding to nucleotides 5000 to 9000. This analysis enables open reading frame 25 to be identified. It begins at the ATG at position 5060 and ends at the TAG at position 8885.

D. Sequence corresponding to nucleotides 9000 to 9700. This analysis enables open reading frame 26 to be identified. It begins at the ATG at position 9034 and ends at the TGA position 9676.

E. Sequence corresponding to nucleotides 9600 to 13144. This analysis enables open reading frames 27, 28, 29 and 30 to be identified. They begin, respectively, at the ATGs at positions 9678, 10895, 11656 and 13059, and end at the stop codons at positions 10101, 10304, 12181 and 12366. Open reading frames 28 and 30 occur on the strand complementary to the coding strand corresponding to all the other open reading frames.

FIG. 46 : 13.4-kb EcoRI-BglII-EcoRI-BglII fragment, positions of the insertions of transposons Tn5Sp into the 9.1-kb EcoRI fragment, positions of the insertions of transposons Tn5 into the insert of plasmid pXL189 as well as the inserts of the various plasmids used during the experiments on complementation of strains SC510 Rif r ::Tn5Sp. The complementations of the mutants SC510 Rif r ::Tn5Sp by the plasmids are indicated (+)—between 5% and 100% of the level of the parent strain SC510 Rif r -(.)—partial complementation, between 0.5 and 5% of the level of SC510 Rif r -, or (−)—absence of complementation, i.e. less than one thousand times less than SC510 Rif r -, positioned immediately above the lines showing diagrammatically the insert of the plasmids and aligned with the insertion sites of the corresponding mutants. Below the mapping of the insertions of transposons Tn5 into the insert of plasmid pXL189, the complementation (+) or absence of complementation (−) of these mutant plasmids for the Agrobacterium tumefaciens mutants G632 and G633 is shown. On the right-hand part of the figure, there is a table showing the complementation of the mutants G622, G623 and G630 (Cameron et al., 1989) by different plasmids; (+)—total complementation, 100% of the level of the parent strain C58C9 Rif r -, (.)—partial complementation, between 10 and 50% of the level of C58C9 Rif r -, or (−)—absence of complementation.

The different plasmids whose insert is shown are constructed as follows (the fragments are excised either from pXL156 or from pXL157): pXL618 corresponds to the 2.5-kb EcoRI-BamHI fragment cloned at the same sites of pKT230 (Bagdasarian et al., 1981); pXL593 corresponds to the 3.1-kb BamHI fragment cloned at the BamHI site of pKT230 (Bagdasarian et al., 1981); pXL623 corresponds to the 1.9-kb BamHI-XhoI fragment cloned at the BamHI-SalI sites of pXL59 (Cameron et al., 1989); pXL1909 corresponds to the 8.4-kb BamHI-BamHI-BamHI fragment cloned at the BamHI of pKT230 (Bagdasarian et al., 1981); pXL221 corresponds to the 1.6-kb EcoRI-ClaI fragment cloned at the same sites of pXL59 (the ClaI site into which this fragment is cloned is the ClaI site of the multisite of pXL59) (Cameron et al., 1989); pXL1908 and 1938 correspond to the same insert, 6.5-kb XhoI-BamHI-BamHI fragment, to which XbaI linkers have been added; this insert is cloned in both orientations at the XbaI site of pXL435 (Cameron et al., 1989); an arrow positioned on the figure indicates the position of the kanamycin resistance gene with respect to the ends of the insert of the two plasmids; pXL208 corresponds to the 5.2-kb BamHI fragment cloned at the BamHI site of pKT230 (Bagdasarian et al., 1981); pXL297 corresponds to the 9.1-kb EcoRI fragment cloned at the EcoRI site of pKT230 (Bagdasarian et al., 1981).

The open reading frames (ORF) defined by the sequencing of the fragment (ORF 22 to 30) are shown, as well as the corresponding cob genes; an arrow indicates the polarity of the transcription.

E, EcoRI; B, BamHI; Bg, BglII; Cl, ClaI; Sau, Sau3AI; X, XhoI;

FIGS. 47 A- 47 P: Coding sequences of each of the genes of the 13.4-kb fragment, cobQ, cobP and cobW, cobN and cobO, respectively, are indicated. The sequences of the COBQ, COBP, COBW, COBN and COBO proteins encoded by these sequences appear under their respective coding sequence cobQ, cobP, cobW, cobN and cobO. The legend is identical to that for FIG. 15 .

FIGS. 48 A- 48 B: A—NH 2 -terminal sequence of SUMT of M. ivanovii and sequence of the oligonucleotides 923, 946, 947; -, means that, at this position, the residue could not be determined; for the antisense oligonucleotide, the amino acids indicated below the sequence correspond to the anticodons shown. B—Presentation of the enzymatic amplification of a fragment internal to the structural gene of SUMT of M. ivanovii with the oligonnucleotides 946 and 947.

FIG. 49 : Construction of the recombinant replicative form pG10. The 615-bp fragment obtained by amplification is digested with HindIII and EcoRI and then purified as described. This fragment is then ligated with the replicative form of phage M13mp19 digested with the same enzymes. The recombinant clone is found as described in the text.

FIG. 50 : Autoradiograph of a genomic DNA blot of M. ivanovii digested with various enzymes, separated by agarose gel electrophoresis and then transferred onto a nylon membrane as described previously. The membrane is hybridised with the pG10probe as described previously. 1, HindIII-BglII; 2, KpnI-BglII; 3, EcoRI-BglII; 4, BglII-PstI. The sizes of the different fragments which hybridise with the probe are shown in kb.

FIGS. 51 A- 51 B: Nucleotide sequence of both strands of the 955-bp fragment of M. ivanovii (SEQ ID NO: 52). The strand situated at the top is to be read from 5′ to 3′ in the left-to-right direction.

FIGS. 52 A- 52 C: Coding sequence of the corA gene of M. ivanovii obtained from the 955-bp sequence (nucleotides of 34-729 SEQ ID NO: 52). The primary sequence of the CORA protein is also shown (SEQ ID NO: 53). The amino acids are shown above their codon and the stop codon is designated by a star. The main physical properties of the CORA protein of M. ivanovii , namely the amino acid composition, in number and in percentage, the molecular weight, the index of polarity, the isoelectric point and the optical density at 280 nm of a solution containing 1 mg/l of purified protein. The hydrophobicity profile of the CORA protein of M. ivanovii ; this profile was obtained on the basis of the programme of Hopp and Woods (1981). Positive values correspond to regions of the protein which are hydrophilic. The position of the amino acids is indicated as abscissa, and the value of the index of hydrophilicity as ordinate; when this value is positive, this indicates that the protein is hydrophilic in this region.

FIG. 53 : Comparison of the primary sequences of the proteins COBA of P. denitrificans (amino acids 17-251 of SEQ ID NO: 54) and CORA of M. ivanovii (amino acids 3-227 of (SEQ ID NO: 54). The proteins have been aligned by means of the programme of Kanehisa (1984). identical amino acids; -, homologous amino acids on the basis of the criteria defined above (see FIGS. 22 and 23 ).

FIGS. 54 A- 54 B: Construction of plasmids pXL1832 and pXL1841.

The legends described, placed on the figure, enable the constructions to be followed.

FIG. 55 : Purification of Pseudomonas denitrificans cobinamide kinase-cobinamidephosphate guanylyl transferase.

The classical methods of molecular biology, such as centrifugation of plasmid DNA in a caesium chloride/ethidium bromide gradient, digestions with restriction enzymes, gel electrophoresis, electroelution of DNA fragments from agarose gels, transformation in E. coli , and the like, are described in the literature (Maniatis et al., 1982, Ausubel et al., 1987).

Restriction enzymes were supplied by New-England Biolabs (Biolabs), Bethesda Research Laboratories (BRL) or Amersham Ltd (Amersham). Linker oligonucleotides were supplied by Biolabs.

For the ligations, the DNA fragments are separated according to their size on 0.7% agarose or 8% acrylamide gels, purified by electroelution, extracted with phenol, precipitated with ethanol and then incubated in 50 mM Tris-HCl buffer pH 7.4, 10 mM MgCl 2 , 10 mM DTT, 2 mM ATP, in the presence of phage T4 DNA ligase (Biolabs).

If necessary, DNA fragments having protuberant 5′ ends are dephosphorylated by a treatment with calf intestinal alkaline phosphatase (CIP, Pharmacia) at 37° C. for 30 min in the following buffer: 100 mM glycine, 1 mM MgCl 2 , 1 mM ZnCl 21 pH 10.5. The same technique is used for dephosphorylation of protuberant or blunt 3′ ends, but the treatment is for 15 min at 37° C. and then 15 min at 56° C. The enzyme is inactivated by heating the reaction mixture to 68° C. for 15 min in the presence of 1% SDS and 100 mM NaCl, followed by a phenol/chloroform extraction and an ethanol precipitation.

Filling-in of protuberant 5′ ends is performed with the Klenow fragment of E. coli DNA polymerase I (Biolabs). The reaction is performed at room temperature for 30 min in 50 mM Tris-HCl buffer pH 7.2, 0.4 mM dNTPs, 10 mM MgSO 4 , 0.1 mM DTT, 50 mg/ml BSA. Filling-in of protuberant 3′ ends is performed in the presence of phage T4 DNA polymerase (Biolabs) according to the manufacturer's recommendations. Digestion of the protuberant ends is performed by limited treatment with S1 nuclease (BRL) according to the manufacturer's recommendations. Linker oligonucleotides are added onto ends of DNA fragments as already described (Maniatis, 1982).

In vitro mutagenesis with oligodeoxynucleotides is performed according to the method developed by Taylor et al., 1985, using the kit distributed by Amersham.

The ligated DNAs are used for transforming the strain rendered competent: E. coli MC 1060 [D(lacIOPZYA)X74, galU, galK, strA r , hsdR] for plasmids or E. coli TG1[D(lac proA,B), supE, thi, hsdD5/F′ traD36, proA + , B + , lacI q , lacZDM15] for replicative forms of phages derived from bacteriophage M13.

Plasmid DNAs are purified according to the technique of Birnboim and Doly, 1979. Minipreparations of plasmid DNA are made according to the protocol of Klein et al., 1980. Preparations of chromosomal DNA of Gram-negative bacteria are produced as already described (Cameron et al., 1989).

Radioactive probes are prepared by nick translation according to the method already detailed (Rigby et al., 1977). Hybridisations between DNA sequences as well as the immobilisation of nucleic acids on nitrocellulose membranes are performed as already described (Cameron et al., 1989). In clonings for which there is a small probability of finding the desired recombinant clone, the latter are found after hybridisation on filters as already described (Maniatis et al., 1982).

The nucleotide sequence of DNA fragments is determined by the chain-termination method (Sanger et al., 1977). In the reaction mixture, dGTP is replaced by 7-deaza-dGTP, in order to avoid compression of bands during acrylamide gel electrophoresis caused by the high percentage of GC in the DNA.

The culture media used for the bacteriological part have already appeared (Maniatis et al., 1982). Culturing in PS4 medium is carried out as already described (Cameron et al., 1989); Pseudomonas denitrificans strains SC510 Rif r and G2 Rif r are cultured in PS4 medium as follows: 250-ml Erlenmeyers containing PS4 medium (25 ml), with, if necessary, the selective antibiotic for the plasmid carried by each strain, are inoculated with a 1/100 dilution of saturated preculture in L medium (Miller 1972), with, if necessary, the selective antibiotic for the plasmid carried by each strain; these cultures are incubated for 6 days at 30° C. and the musts are then analysed for their cobalamin content or alternatively the enzymatic activity of some enzymes of the pathway. Strains of. Agrobacterium tumefaciens, Pseudomonas putida and Rhizobium meliloti are cultured at 30° C.; except where otherwise stated, they are cultured in L medium.

Bacterial conjugations are carried out as already described (Cameron et al., 1989).

Extracts of total proteins are produced as already described (Ausubel et al., 1987).

Analytical electrophoresis (SDS-PAGE) of proteins in acrylamide gel under denaturing conditions is performed as already described (Ausubel et al., 1987). The PhastSystem apparatus (Pharmacia) using Laemli's discontinuous-buffer system (Laemli, 1970) is also used; different gels are used in accordance with the molecular weights of the proteins to be analysed as well as their purity:

PhastGel gradient 8-25

PhastGel Homogeneous 12.5

Staining is performed either with Coomassie blue with the aid of PhastGel Blue R (Pharmacia), or with silver nitrate using the PhastGel silver Kit (Pharmacia) in accordance with the manufacturer's instructions.

NH 2 -terminal sequences of the proteins are determined by the Edman degradation technique, using an automated sequencer (Applied Biosystems model 407A) coupled to an HPLC apparatus for identification of the phenylthiohydantoin derivatives.

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GGGCTGCAGG TCGACTCTAG AATCGATGAA GCCTGCGATG AAGGCGGCGA CGAACAGGAA 60

GGCGAGCAGG TGGAAGGCGA GATCTTGCAC GGCGGGGACT CGAGAGGAGA GCTGTCAGGC 120

GGGATTTTCC GCCTTGTGTC AGAGCCCGGC GCGATTTGCA AAGCCTTCTG TCGCGGTGTT 180

GCTGTCCATG CAGGTGTCGA AATTGAAAAA CCGACAAAGA TTCACAGCCT TGTTCCAGCT 240

CGCTGTCTTT CTGGATGGAG GCGCTCTCGC CCGCATGGTG CCGAAGAAGG GCTGTCCTTG 300

CGATACGGTA GGCGGATGAC GATCTTCCTC AAACGCGACA TGGCGATGGC GCAATCCGGT 360

TTGACCGGCC TTCCGCGCTC CGGTAAAAAT GAAGGATATG CGACGGCGTC CGCTTTGGCG 420

GACTGAAAGA GCGTCCGGTG CGGCCGACCC AGTCAGGGGG GCATCAGCCG GTGCTGTCCA 480

GATCGGCCGG GACGGATCGT CCCAGCCGGC GCTTCGTTAA GGAGAACAAC GAAGGGAGCC 540

GGCCGCCGAT GCCATCGGGC CAACACTCTG CACAGACGAC GAAAGCAGGA GCCGGGCTGG 600

TGCTCGGGCT CGGCTGCGAG CGTCGCACGC CGGCCGAAGA GGTGATCGCC CTTGCCGAGC 660

GTGCGCTTGC CGATGCCGGT GTTGCGCCCG GCGATCTGCG GCTGGTCGCC TCGCTCGATG 720

CTCGCGCCGA GGAGCCGGCG ATCCTGGCGG CCGCTCAGCA TTTCGCGGTT CCGGCCGCGT 780

TCTACGATGC CGCCACGCTC GAAGCCGAAG CTTCCCGGCT CGCCAACCCG TCCGAGATCG 840

TCTTTGCCTA CACGGGTTGT CATGGCGTTG CCGAGGGTGC AGCGCTCGTC GGCGCCGGTC 900

GCGAAGCCGT GCTGATTGTG CAGAAGATCG TCTCCGCCCA TGCGACGGCC GCACTTGCCG 960

GGCCGGCGAC CTTGCGCGCC GAAAAGCGCA TCCAGGCGGC GGAGGCTGTC TGATGCATTC 1020

TTATGTTGTT GAATTGAATC AATCTTTTGC CCGGGGTTTC TCTCAAGTGG AATCCGGTTC 1080

TTTAGAGAGC GCGTCAGGCG TGCCGTTGGG TGGCGCCGAA ATACAGGTGG GACAGCACGC 1140

ATGATCGACG ACCTCTTTGC CGGATTGCCG GCGCTCGAAA AAGGTTCGGT CTGGCTGGTC 1200

GGCGCCGGCC CCGGCGATCC CGGCCTGTTG ACGCTGCATG CGGCCAATGC GCTGCGCCAG 1260

GCGGATGTGA TCGTGCATGA TGCGCTGGTC AACGAGGATT GCCTGAAGCT CGCGCGGCCG 1320

GGCGCCGTGC TGGAGTTTGC GGGCAAGCGT GGCGGCAAGC CGTCGCCGAA GCAGCGCGAC 1380

ATCTCGCTTC GCCTCGTCGA ACTCGCGCGC GCCGGCAACC GGGTGCTGCG CCTCAAAGGC 1440

GGCGATCCCT TCGTCTTCGG TCGCGGTGGC GAGGAGGCGC TGACGCTGGT CGAACACCAG 1500

GTGCCGTTCC GAATCGTGCC CGGCATCACC GCCGGTATCG GCGGGCTTGC CTATGCCGGC 1560

ATTCCCGTGA CCCATCGCGA GGTCAACCAC GCGGTCACTT TCCTGACTGG CCATGATTCC 1620

TCCGGCCTGG TGCCGGATCG CATCAACTGG CAGGGCATCG CCAGCGGCTC GCCTGTCATC 1680

GTCATGTACA TGGCGATGAA ACATATCGGC GCGATCACCG CCAACCTCAT TGCCGGCGGC 1740

CGCTCGCCGG ACGAACCGGT CGCCTTCGTC TGCAACGCCG CGACGCCGCA GCAGGCGGTG 1800

CTGGAAACGA CGCTTGCGCG TGCAGAGGCC GATGTTGCGG CGGCAGGGCT GGAGCCGCCG 1860

GCGATCGTCG TCGTCGGCGA GGTGGTGCGG CTGCGCGCAG CGCTCGACTG GATCGGCGCG 1920

CTGGACGGGC GCAAGCTTGC CGCCGACCCG TTCGCCAATC GCATTCTCAG GAACCCGGCA 1980

TGAGCGGATT GCTGATTGCC GCACCCGCGT CCGGCTCCGG CAAGACGACG GTGACGCTCG 2040

GGCTGATGCG CGCCCTGAAG AGGCGCGGCG TGGCGATCGC GCCCGGCAAG GCGGGGCCGG 2100

ACTATATCGA TCCCGCTTTC CACGCGGCAG CGACCGGCGA GCCCTGCTTC AACTACGACC 2160

CCTGGGCGAT GCGCCCGGAA CTGCTGCTTG CCAATGCGTC GCATGTGGCC TCCGGCGGGC 2220

GCACATTGAT CGTCGAGGCG ATGATGGGAC TGCATGACGG TGCTGCCGAC GGCTCGGGAA 2280

CGCCAGCGGA CCTCGCCGCG ACGCTGAACC TTGCGGTCAT TCTGGTGGTC GATTGCGCCC 2340

GCATGTCCCA GTCGGTTGCC GCCCTCGTGC GCGGCTATGC GGATCATCGC GACGATATCC 2400

GGGTGGTTGG CGTCATCCTC AACAAGGTCG GCAGCGATCG GCATGAAATG ATGCTGCGCG 2460

ATGCGCTCGG CAAGGTGCGC ATGCCTGTCT TCGGCGTGCT CCGGCAGGAC AGCGCATTGC 2520

AACTGCCGGA GCGCCATCTC GGGCTCGTGC AGGCGGGCGA ACACTCAGCG CTTGAGGGCT 2580

TCATCGAGGC GGCGGCCGCG CGGGTCGAGG CTGCCTGCGA TCTCGACGCC ATCCGCCTGA 2640

TCGCGACGAT TTTCCCGCAG GTGCCCGCGG CGGCCGATGC CGAGCGTTTG CGGCCGCTCG 2700

GTCAGCGCAT CGCGGTCGCG CGCGATATCG CCTTTGCCTT CTGCTACGAG CACCTGCTTT 2760

ACGGCTGGCG GCAAGGCGGC GCGGAGATTT CCTTCTTCTC GCCGCTCGCC GACGAGGGGC 2820

CGGATGCGGC AGCCGATGCC GTCTATCTTC CGGGGGGTTA TCCGGAGCTG CATGCGGGGC 2880

AGCTGAGCGC CGCCGCCCGA TTCCGTTCCG GCATGCATTC CGCGGCGGAA CGCGGCGCCC 2940

GCATCTTCGG CGAGTGCGGC GGCTATATGG TGCTCGGCGA AGGGCTTGTC GCTGCCGATG 3000

GCACACGCTA CGACATGCTC GGCCTGCTGC CGCTCGTAAC CAGTTTTGCC GAGCGCAGGC 3060

GGCACCTCGG CTATCGCCGC GTCGTGCCTG TCGACAACGC CTTCTTCGAT GGACCCATGA 3120

CGGCGCACGA ATTCCACTAT GCGACCATCG TCGCCGAAGG GGCGGCCGAT CGGCTGTTTG 3180

CGGTCAGCGA CGCCGCCGGC GAGGATCTCG GCCAGGCGGG CCTCCGGCGC GGCCCTGTCG 3240

CCGGTTCCTT CATGCATCTG ATCGACGTCG CAGGTGCTGC ATGAGCGCAC CGATCGTTCA 3300

TGGTGGCGGC ATCACCGAGG CCGCAGCGCG CTATGGCGGC CGGCCTGAAG ACTGGCTCGA 3360

TCTGTCGACC GGCATCAATC CATGCCCCGT CGCCTTGCCC GCGGTCCCTG AGCGCGCCTG 3420

GCACCGGCTG CCGGATCGGC AGACGGTAGA TGATGCGCGG AGCGCCGCCG CCGACTACTA 3480

CCGCACCAAC GGCGTGCTGC CTTTGCCGGT GCCGGGCACC CAGTCGGTGA TCCAGCTCCT 3540

GCCACGTCTT GCTCCGGCCA ACAGGCACGT CGCGATTTTC GGGCCGACCT ATGGCGAGTA 3600

TGCCCGCGTG CTTGAAGCGG CCGGCTTTGC TGTCGATCGC GTCGCGGATG CCGACGCGCT 3660

CACGGCCGAA CATGGGCTTG TCATCGTCGT CAACCCCAAC AACCCGACCG GCCGCGCCTT 3720

GGCGCCGGCG GAGCTTCTGG CGATCGCCGC AAGGCAGAAG GCGAGCGGCG GACTGCTGCT 3780

GGTCGATGAG GCCTTCGGCG ATCTTGAGCC GCAACTGAGT GTCGCTGGTC ACGCGTCAGG 3840

GCAAGGCAAC CTCATCGTCT TCCGCTCCTT CGGCAAGTTC TTCGGCCTTG CGGGCCTGCG 3900

CCTCGGCTTC GTCGTTGCGA CCGAGCCAGT GCTTGCATCC TTTGCCGATT GGCTCGGTCC 3960

CTGGGCTGTC TCCGGCCCGG CGTTGACGAT CTCGAAAGCG CTGATGCAGG GCGATACGAA 4020

GGCGATCGCG GCGGGCATCC TCGAGCGTCG CGCCGGCCTC GATGCGGCTC TCGATGGGGC 4080

AGGGCTCAAC CGTATCGGCG GCACGGGGCT ATTCGTGCTG GTCGAGCATC CCAGGGCAGC 4140

TCTGCTGCAG GAGCGGCTCT GCGAGGCCCA TATTCTCACG CGCAAGTTCG ACTATGCCCC 4200

GACCTGGCTC AGGGTCGGTC TTGCGCCTGA CGCGGCTGGT GACCGACGGC TGGCGGACGC 4260

GCTTGCCCGC ATGGAGCTCT GAGGTGTCGG AGACGATCCT GCTCATTCTC GCGCTGGCGC 4320

TGGTGATCGA CCGCGTTGTC GGCGATCCGG ACTGGCTCTG GGCGCGCGTG CCGCATCCGG 4380

TCGTGTTTTT CGGCAAGGCC ATCGGCTTTT TCGACGCGCG GCTGAACCGG GAGGACCTCG 4440

AGGATAGCGC GCGCAAATTT CGTGGCGTCG TCGCGATCCT TTTGTTGCTT GGCATCAGCG 4500

CCTGGTTCGG CCATCTGCTG CATCGCCTGT TCGCCGTCCT CGGACCGCTC GGCTTTCTGC 4560

TCGAGGCGGT TCTGGTCGCG GTCTTCCTGG CACAGAAGAG CCTCGCCGAT CACGTGCGTC 4620

GCGTGGCCGG GGGCTTGCGA CAGGGCGGGC TGGAAGGCGG GCGTGCCGCC GTGTCGATGA 4680

TCGTTGGTCG CGATCCAAAG ACGCTCGACG AGCCGGCGGT CTGCCGTGCC GCGATCGAAA 4740

GCCTTGCCGA GAATTTCTCC GACGGCGTCG TGGCGCCGGC CTTCTGGTAC GCGGTTGCCG 4800

GCCTGCCGGG GCTTCTTGCC TACAAGATGC TGAACACCGC CGATTCGATG ATCGGCCACA 4860

AGTCGCCGAA ATATCTGCAC TTCGGCTGGG CCTCGGCCCG ACTCGACGAT CTCGCCAACC 4920

TGCCGGCAGC GAGGCTCTCG ATCCTTTTGA TCTCAGCCGG TGCGCTGATC CATCGTGGCG 4980

CCAGCGCCGC CAAGGATGCG CTGACCGTGG CCCTTCGCGA CCATGGCCTG CACCGCTCGC 5040

CGAACTCCGG CTGGCCGGAA GCGGCCATGG CCGGCGCGCT CGATCTGCAG CTTGCCGGTC 5100

CGCGGATCTA TGGCGGCGTC AAGGTCAGCG AACCTATGAT CAACGGTCCG GGCCGAGCGG 5160

TTGCAACAAG CGAAGACATC GACGCCGGTA TTGCTGTATT TTATGGCGCC TGTACGGTCA 5220

TGGCCGGGTT TGTTCTTGCA ATCGCAATGA TTTGATCGCG GAAGTTGACC TTCGCATTAA 5280

GACTCTGCTT TCCATATGTA TTAAGATCGT ATCATATTCG ATCAGTTATT CTCCTGGAAC 5340

GTTTGGTTCC ACCGGTACGT GTTCGTCTTC CCGGAGAGAG AAGCATGCGC AAAAGCTT 5398

GAATTCGCCA GCGCCTACAT GGCTGACCTC AAGCAGTTCC TCGTGGCCCA GAAGAACGAG 60

GGCCGGCAGA TTTTCCCTCG CGGGCCTGAG TATTTTCGCG CGCTCGACCT GACGCCGCTC 120

GACAAGGTGC GCGTGGTCAT TCTCGGCCAG GATCCCTATC ACGGTGACGG CCAGCGGCAT 180

GGGCTCTGCT TCAGCGTTCG CCCCGGTGTC CGGACGCCGC CGTCGCTGGT CAACATCTAC 240

AAGGAACTGA ATACCGATCT CGGTATTCCG CCGGCGCGTC ACGGTTTTCT CGAAAGCTGG 300

GCAAGGCAGG GCGTGCTGCT TTTGAACAGC GTGCTGACGG TAGAGCGCGG GAACGTGCGT 360

CACACCAGGG TCACGGTTGG GAAAAGTTCA CGGATGCGAT CATCCGTGCG GTCAACGAGG 420

CCGAGCATCC CGTCGTCTTC ATGCTTTGGG GCTCCTATGC GCAGAAGAAG GCGGCCTTCG 480

TCGACCGCTC GCGCCATCTT GTCCTGAGGG CACCACATCC GTCGCCGCTC TCAGCCCATT 540

CCGGCTTTCT CGGCTGCCGG CATTTTTCCC AGGCCAATGC CTTCCTCGAA AGCAAAGGCT 600

TCGATCCGAT CGACTGGCGG CTGCCGGAAA ATCCGGCTGC GGACATCAAC TGAAGGCTTG 660

GCGCGAATGA CGGCTTTGTC GTCGCCCTGA GGTCTTGCCT TGGCGGCGGC GATCCGCCTA 720

AGACGCCCGA ACGAAATGGC GGAGGCGGGC ATGCGCAAAA TTCTGATCAT CGGCATCGGT 780

TCGGGCAATC CCGAACACAT GACCGTGCAG GCGATCAACG CGCTGAACTG CGCCGACGTG 840

CTCTTTATCC CGACCAAGGG AGCGAAGAAG ACCGAGCTTG CCGAAGTGCG CCGCGACATC 900

TGCGCCCGCT ACGTCACGCG CAAGGACAGC CGCACCGTCG AGTTCGCGGT GCCCGTGCGG 960

CGCACCGAAG GCGTCAGCTA TGACGGCAGC GTCGATGACT GGCACGCCCA GATCGCTGGG 1020

ATTTACGAAG CGCTTCTATC GAAGGAGTTG GGCGAAGAGG GAACTGGCGC GTTTCTCGTC 1080

TGGGGCGACC CGATGCTCTA TGACAGCACC ATTCGCATCG TCGAGCGGGT CAAGGCACGC 1140

GGTGAGGTCG CCTTCGCCTA CGACGTCATT CCCGGGATCA CCAGTCTGCA GGCGCTTTGC 1200

GCCAGCCACC GCATTCCGCT GAACCTCGTC GGCAAGCCGG TGGAGATCAC CACGGGGCGT 1260

CGGCTGCACG AAAGCTTTCC CGAGAAGAGC CAGACCTCGG TCGTCATGCT CGATGGCGAA 1320

CAGGCGTTTC AGCGGGTCGA GGACCCGGAG GCGGAGATCT ATTGGGGCGC CTATCTCGGC 1380

ACGCGGGATG AGATCGTCAT TTCCGGCCGC GTGGCTGAGG TGAAGGACCG GATCCTTGAA 1440

ACGCGGGCGG CGGCGCGCGC GAAGATGGGA TGGATCATGG ACATCTATCT CCTGCGCAAG 1500

GGCGCCGACT TCGACGAGTG ACGGGGAGGG CCGATCTGCG TCGTGTTTGA TCTCACTCAA 1560

GGTTTGCGGC TGTGTTATAG CGTCTTAAGA GGCTTCTTCA GGGAGGAGAA CCTCAAGTGA 1620

TGACGGATTT GATGACCAGC TGCGCCCTTC CATTGACCGG AGATGCCGGC ACCGTCGCTT 1680

CGATGCGCCG CGGCGCCTGC CCGTCCTTGG CAGAGCCGAT GCAGACCGGC GACGGCCTGC 1740

TCGTGAGGGT GAGGCCAACG GATGACAGCC TGACGCTGCC GAAGGTCATT GCCCTTGCCA 1800

CGGCTGCCGA GCGCTTCGGC AATGGCATCA TCGAGATTAC CGCGCGCGGA AACCTGCAGC 1860

TTCGCGGCCT GAGCGCGGCT TCGGTGCCAA GGCTGGCGCA GGCGATCGGC GATGCGGAGA 1920

TCGCCATTGC CGAGGGGCTC GCGATCGAGG TGCCGCCCCT GGCCGGCATC GACCCGGACG 1980

AGATCGCCGA TCCGCGGCCG ATTGCCACTG AGCTTCGTGA AGCGTTGGAT GTGCGCCAGG 2040

TGCCGTTGAA GCTTGCACCC AAATTATCCG TCGTCATCGA TAGCGGTGGC CGGTTTGGTC 2100

TCGGCGCTGT CGTCGCCGAC ATTCGCCTTC AGGCGGTTTC GACTGTCGCG GGGGTGGCCT 2160

GGGTGCTGTC GCTTGGCGGC ACGTCAACGA AGGCATCGAG CGTCGGGACG TTGGCCGGCA 2220

ACGCGGTCGT GCCGGCCCTG ATCACCATTC TCGAGAAACT GGCGAGCCTG GGCACGACGA 2280

TGCGCGGGCG CGATCTGGAC CCGTCGGAAA TCCGCGCGCT CTGTCGCTGT GAGACATCGT 2340

CCGAACGCCC GGCCGCTCCG CGTTCGGCCG CAATACCCGG CATTCATGCG CTGGGTAACG 2400

CCGACACCGT TCTCGGCCTC GGTCTGGCCT TTGCTCAGGT GGAGGCCGCC GCGCTGGCAT 2460

CCTACCTGCA TCAGGTCCAG GCGCTTGGCG CCAATGCGAT CCGGCTTGCG CCCGGGCACG 2520

CCTTCTTCGT CCTCGGCCTT TGCCCCGAGA CCGCGGCTGT GGCGCAGAGC CTGGCAGCGT 2580

CACACGGTTT TCGCATTGCC GAGCAGGATC CGCGCAATGC GATCGCCACC TGCGCCGGCA 2640

GCAAGGGTTG CGCCTCGGCG TGGATGGAAA CCAAGGGCAT GGCCGAGCGC CTCGTCGAGA 2700

CGGCGCCGGA ATTGCTCGAC GGGTCGCTCA CCGTGCATCT CTCCGGCTGC GCCAAGGGCT 2760

GCGCCCGGCC GAAGCCGTCC GAACTGACGC TTGTCGGTGC GCCATCAGGA TACGGGCTTG 2820

TCGTAAATGG GGCTGCCAAT GGCTTGCCAA GCGCCTACAC CGATGAGAAT GGAATGGGAT 2880

CCGCCCTTGC CCGGCTCGGC CGGCTGGTGC GGCAAAACAA AGACGCTGGC GAATCGGCGC 2940

AGTCCTGTCT TACACGGCTC GGAGCTGCGC GCGTCTCGGC AGCGTTCGAA CAGGGATAGA 3000

CATGCCTGAG TATGATTACA TTCGCGATGG CAACGCCATC TACGAGCGTT CCTTCGCCAT 3060

CATCCGCGCC GAGGCCGATC TGTCGCGCTT CTCCGAAGAG GAAGCGGATC TGGCTGTGCG 3120

CATGGTGCAC GCCTGCGGTT CCGTCGAGGC GACCAGGCAG TTCGTGTTTT CTCCCGATTT 3180

CGTAAGCTCG GCCCGTGCGG CGCTGAAAGC CGGTGCGCCG ATCCTCTGCG ATGCCGAGAT 3240

GGTTGCGCAC GGTGTCACCC GCGCCCGTCT GCCGGCCGGC AACGAGGTGA TCTGCACGCT 3300

GCGCGATCCT CGCACGCCCG CACTTGCGGC CGAGATCGGC AACACCCGCT CCGCCGCAGC 3360

CCTGAAGCTC TGGAGCGAGC GGCTGGCCGG TTCGGTGGTC GCGATCGGCA ACGCGCCGAC 3420

GGCGTTGTTC TTCCTCTTGG AAATGCTGCG CGACGGCGCG CCGAAGCCGG CGGCAATCCT 3480

CGGCATGCCC GTCGGTTTCG TCGGTGCGGC GGAATCGAAG GATGCGCTGG CCGAGAACTC 3540

CTATGGCGTT CCCTTCGCCA TCGTGCGCGG CCGCCTCGGC GGGAGTGCCA TGACGGCGGC 3600

AGCGCTTAAC TCGCTCGCGA GGCCGGGCCT GTGAGCGGCG TCGGCGTGGG GCGCCTGATC 3660

GGTGTTGGGA CCGGCCCCGG TGATCCGGAA CTTTTGACGG TCAAGGCGGT GAAGGCGCTC 3720

GGGCAAGCCG ATGTGCTTGC CTATTTCGCC AAGGCCGGGC GAAGCGGTAA CGGCCGCGCG 3780

GTGGTCGAGG GTCTGCTGAA GCCCGATCTT GTCGAGCTGC CGCTATACTA TCCGGTGACG 3840

ACCGAAATCG ACAAGGACGA TGGCGCCTAC AAGACCCAGA TCACCGACTT CTACAATGCG 3900

TCGGCCGAAG CGGTAGCGGC GCATCTTGCC GCCGGGCGCA CGGTCGCCGT GCTCAGTGAA 3960

GGCGACCCGC TGTTCTATGG TTCCTACATG CATCTGCATG TGCGGCTCGC CAATCGTTTC 4020

CCGGTCGAGG TGATCCCCGG CATTACCGCC ATGTCCGGCT GTTGGTCGCT TGCCGGCCTG 4080

CCGCTGGTGC AGGGCGACGA CGTGCTCTCG GTGCTTCCGG GCACCATGGC CGAGGCCGAG 4140

CTCGGCCGCA GGCTTGCGGA TACCGAAGCC GCCGTGATCA TGAAGGTCGG GCGCAATTTG 4200

CCGAAGATCC GTCGGGCGCT CGCTGCCTCC GGCCGTCTCG ACCAGGCCGT CTATGTCGAA 4260

CGCGGCACGA TGAAGAACGC GGCGATGACG GCTCTTGCGG AAAAGGCCGA CGACGAGGCG 4320

CCCTATTTCT CGCTGGTGCT CGTTCCCGGC TGGAAGGACC GACCATGACC GGTACGCTCT 4380

ATGTCGTCGG TACCGGACCG GGCAGCGCCA AGCAGATGAC GCCGGAAACG GCGGAAGCCG 4440

TTGCGGCCGC TCAGGAGTTT TACGGCTACT TTCCCTATCT CGACCGGCTG AACCTCAGAC 4500

CGGATCAGAT CCGTGTCGCC TCGGACAACC GCGAGGAGCT CGATCGGGCA CAGGTCGCGC 4560

TGACGCGGGC TGCGGCAGGC GTGAAGGTCT GCATGGTCTC CGGTGGCGAT CCCGGTGTCT 4620

TTGCCATGGC GGCCGCCGTC TGCGAGGCGA TCGACAAGGG ACCGGCGGAA TGGAAGTCGG 4680

TTGAACTGGT GATCACGCCC GGCGTGACCG CGATGCTCGC CGTTGCCGCC CGCATCGGCG 4740

CGCCGCTCGG TCATGATTTC TGTGCGATCT CGCTTTCCGA CAATCTGAAG CCCTGGGAAG 4800

TCATCACCCG GCGTCTCAGG CTGGCGGCGG AAGCGGGCTT CGTCATTGCC CTCTACAATC 4860

CGATCAGCAA GGCGCGGCCC TGGCAGCTCG GTGAGGCCTT CGAGCTTCTG CGCAGCGTTC 4920

TGCCGGCAAG CGTTCCGGTC ATCTTCGGCC GTGCGGCCGG GCGGCCGGAC GAACGGATCG 4980

CGGTGATGCC GCTCGGCGAG GCCGATGCCA ACCGCGCCGA CATGGCGACC TGCGTCATCA 5040

TCGGCTCGCC GGAGACGCGC ATCGTCGAGC GCGACGGCCA ACCCGATCTC GTCTACACAC 5100

CGCGCTTCTA TGCAGGGGCG AGCCAGTGAG CGATGCGGTT GAGTGCCTCG TCGCAACTGC 5160

CGACCGTCGG CACGTCCGCG GGCTTGCGCC GCTCGACCAT GATCACCTCG ATGCCGAGCC 5220

GGCGCGCTGC GGCAATCTTG CCGTAGGTGG CGCTGCCACC GCTGTTCTTG GCGACGATCA 5280

CATCGATCTG CCGACTCCTG AGCAACGCGG CTTCGTCGGC TTCCGCAAAG GGACCGGTCG 5340

CCAGGATCGC CTCCTGGTCG GGCAGATTAA GCGGCGGCGT CACCGGATCG ACGCTGCGGA 5400

TGACGTAGCT GTGCTGCGGC GCGACCTCGA AGTGGAAAGC TTCCTGTCGA CCTATCGCCA 5460

GGAAGACGCG GCGTCGCCGA TCACCGAGCG CGCTGACGGC CTCGACAACG CTATCGACAG 5520

CAGTCCAGCG GTCGCCAGGC AGGGGCACCC ATTCCGGTCG GCGGAGGGCG ATAAGCGCAA 5580

CGCCGGTTCT TTGCGCTGCG TCCGCGGCGT TGTGCGAAAT GCGTGCGGCA AAGGGGTGCG 5640

TCGCATCGAC CAGCAGCGCG ATGTTTTCGT CATGCACGAA ATGCGCCAGC CCATCCGCGC 5700

CGCCAAAGCC GCCGATGCGC GTCTTGACCG GCTGCGGCCG CGGGTCCGCG GTGCGGCCGG 5760

CCAGCGAGAT GGCGGTGTCG TAGCGGACAT CTTCGGCCAA GCGGCGCGCG AGTTCGCGTG 5820

CCTCGGTGGT GCCACCCAGA ATCAGAATAC GAGGTTTTTC CATGGCTGAC GTGTCGAACA 5880

GCGAACCCGC CATAGTCTCC CCCTGGCTGA CCGTCATCGG TATCGGTGAG GATGGTGTAG 5940

CGGGTCTCGG CGACGAGGCC AAGCGGCTGA TCGCCGAAGC GCCGGTCGTC TACGGCGGCC 6000

ATCGTCATCT GGAGCTCGCC GCCTCCCTCA TCACCGGCGA AGCGCACAAT TGGCTAAGCC 6060

CCCTCGAACG CTCGGTCGTC GAGATCGTCG CGCGTCGCGG CAGCCCGGTG GTGGTGCTTG 6120

CCTCGGGCGA CCCGTTCTTC TTCGGCGTCG GCGTGACGCT GGCGCGCCGC ATCGCCTCGG 6180

CCGAAATACG CACGCTTCCG GCGCCGTCGT CGATCAGTCT TGCCGCCTCG CGCCTCGGCT 6240

GGGCGCTGCA GGATGCGACG CTCGTCTCCG TACATGGGCG GCCGCTGGAT CTGGTGCGAC 6300

CGCATTTGCA TCCGGGGGCG CGTGTGCTTA CGCTCACGTC GGACGGTGCG GGTCCGCGAG 6360

ACCTTGCCGA GCTTCTGGTT TCAAGCGGCT TCGGTCAGTC GCGACTGACC GTGCTCGAAG 6420

CGCTGGGCGG CGCCGGCGAA CGGGTGACGA CGCAGATCGC CGCGCGCTTC ATGCTCGGCC 6480

TCGTGCATCC TTTGAACGTC TGCGCCATTG AGGTGGCGGC CGACGAGGGC GCGCGCATCC 6540

TGCCGCTTGC CGCCGGCCGC GACGATGCGC TGTTCGAACA TGACGGGCAG ATCACCAAGC 6600

GCGAGGTGCG GGCGCTGACG CTGTCGGCAC TCGCACCGCG CAAGGGCGAA CTGCTATGGG 6660

ACATCGGCGG CGGCTCCGGC TCGATCGGCA TCGAATGGAT GCTCGCCGAT CCGACCATGC 6720

AGGCGATCAC CATCGAGGTT GAGCCGGAGC GGGCAGCGCG CATCGGCCGC AACGCGACGA 6780

TGTTCGGCGT GCCCGGGCTG ACGGTTGTCG AAGGCGAGGC GCCGGCGGCG CTTGCCGGCC 6840

TGCCACAACC GGACGCGATC TTCATCGGCG GCGGCGGCAG CGAAGACGGC GTCATGGAAG 6900

CAGCGATCGA GGCGCTCAAG TCAGGCGGAC GGCTGGTTGC CAACGCGGTG ACGACGGACA 6960

TGGAAGCGGT GCTGCTCGAT CATCACGCGC GGCTCGGCGG TTCGCTGATC CGCATCGATA 7020

TCGCGCGTGC AGGACCCATC GGCGGCATGA CCGGCTGGAA GCCGGCCATG CCGGTCACCC 7080

AATGGTCGTG GACGAAGGGC TAAAGCAGTT CCAGCGAAAG TGTGACGCGG TTTTGCGTCC 7140

GGAACTGCGC AAGAAAAAGA AAGAGTAACC TATGACGGTA CATTTCATCG GCGCCGGCCC 7200

GGGAGCCGCA GACCTGATCA CGGTGCGTGG TCGCGACCTG ATCGGGCGCT GCCCGGTCTG 7260

CCTTTACGCC GGCTCGATCG TCTCGCCGGA GCTGCTGCGA TATTGCCCGC CGGGCGCCCG 7320

CATTGTCGAT ACGGCGCCGA TGTCCCTCGA CGAGATCGAG GCGGAGTATG TGAAGGCCGA 7380

AGCCGAAGGG CTCGACGTGG CGCGGCTTCA TTCGGGCGAC CTTTCGGTCT GGAGTGCTGT 7440

GGCCGAACAG ATCCGCCGGC TCGAGAAGCA TGGCATCGCC TATACGATGA CGCCGGGCGT 7500

TCCTTCCTTT GCGGCGGCGG CTTCAGCGCT CGGTCGCGAA TTGACCATTC CGGCCGTGGC 7560

CCAGAGCCTG GTGCTGACCC GCGTTTCGGG CCGCGCCTCG CCGATGCCGA ACTCAGAAAC 7620

GCTTTCCGCT TTCGGCGCTA CGGGATCGAC GCTGGCAATC CACCTTGCGA TCCATGCGCT 7680

TCAGCAGGTG GTCGAGGAAC TGACGCCGCT CTACGGTGCC GACTGCCCGG TCGCCATCGT 7740

CGTCAAGGCC TCCTGGCCGG ACGAACGCGT GGTGCGCGGC ACGCTCGGTG ACATCGCCGC 7800

CAAGGTGGCG GAAGAGCCGA TCGAGCGCAC GGCGCTGATC TTCGTCGGTC CGGGGCTCGA 7860

AGCCTCCGAT TTCCGTGAAA GCTCGCTCTA CGATCCCGCC TATCAGCGGC GCTTCAGAGG 7920

GCGCGGCGAA TAGGCCGCAC TCCCTCGGGG GTCGGCCTAA GTTTCCCGCT GAGAGGGTTT 7980

TGAAACCTAT TCTGCCGGTT CTTCGCGCGG CGGCCGCTGC TTGAGCGGGA CGCCGCGCTT 8040

TTCCTCGACG CGGTCGCGGT AGAGCGCTGC CTGTCCAAGC AGCATCAGCG TCACCGGCGT 8100

GGTGGCGACG ACGAAGACGA TGATCAGGAT TTCGTGGAAT ACCCAGCGGC TCTGCAGCAC 8160

GGCAAAGCAG ATGATAGAGG CGGCGCAGAT CATCAGTACG CCGCCGCTGG TCGCCAGCGT 8220

CGGTGCGTGC AGGCGCTCGT AGAAGCTGGT GAACCGGAGC AAGCCGACGG AGCCGATCAG 8280

CGCCACTGCG GCGCCGAGGA CGGTGAGCCC GCAGACGAGA ACGGCTGCCC AGACGGGAAG 8340

GTCGGTGAGG TGGCTCATTC GATGATCTCC CCGCGCATCA GGAACTTGCC GAAGGCGATC 8400

GACGAGACGA AGCCGATCAA AGCCACGATC AGGGCGGACT CGAAATAGAG CGAGTTGGCC 8460

GTGCGGATGC CGAAGGTCAA GAGCATCAGC ATGGCGTTGA TATAGAGCGT GTCGAGGCCG 8520

AGGATACGGT CCTGGGCGCG CGGTCCCCTC ACCATGCGAT AGAAGGCAAA AGCCATCGCC 8580

AGGCCGAGCA TGATCTGGGC AATCAGGATC GACCAGATGA TTGAAAGTTC CATCATCCGA 8640

ATATCTCCTT CAGGGCGGTC TCATAGCGCT TGACCGTATC GAGCCAGATG TCCTCGTTCT 8700

CCATGTCGAG CACGTGGAAG AGCAGGGACT TGCGGCCGCG ATCCGGGGAA TTC 8753

ATGATCGACG ACCTCTTTGC CGGATTGCCG GCGCTCGAAA AAGGTTCGGT CTGGCTGGTC 60

GGCGCCGGCC CCGGCGATCC CGGCCTGTTG ACGCTGCATG CGGCCAATGC GCTGCGCCAG 120

GCGGATGTGA TCGTGCATGA TGCGCTGGTC AACGAGGATT GCCTGAAGCT CGCGCGGCCG 180

GGCGCCGTGC TGGAGTTTGC GGGCAAGCGT GGCGGCAAGC CGTCGCCGAA GCAGCGCGAC 240

ATCTCGCTTC GCCTCGTCGA ACTCGCGCGC GCCGGCAACC GGGTGCTGCG CCTCAAAGGC 300

GGCGATCCCT TCGTCTTCGG TCGCGGTGGC GAGGAGGCGC TGACGCTGGT CGAACACCAG 360

GTGCCGTTCC GAATCGTGCC CGGCATCACC GCCGGTATCG GCGGGCTTGC CTATGCCGGC 420

ATTCCCGTGA CCCATCGCGA GGTCAACCAC GCGGTCACTT TCCTGACTGG CCATGATTCC 480

TCCGGCCTGG TGCCGGATCG CATCAACTGG CAGGGCATCG CCAGCGGCTC GCCTGTCATC 540

GTCATGTACA TGGCGATGAA ACATATCGGC GCGATCACCG CCAACCTCAT TGCCGGCGGC 600

CGCTCGCCGG ACGAACCGGT CGCCTTCGTC TGCAACGCCG CGACGCCGCA GCAGGCGGTG 660

CTGGAAACGA CGCTTGCGCG TGCAGAGGCC GATGTTGCGG CGGCAGGGCT GGAGCCGCCG 720

GCGATCGTCG TCGTCGGCGA GGTGGTGCGG CTGCGCGCAG CGCTCGACTG GATCGGCGCG 780

CTGGACGGGC GCAAGCTTGC CGCCGACCCG TTCGCCAATC GCATTCTCAG GAACCCGGCA 840

TGA 843

Met Ile Asp Asp Leu Phe Ala Gly Leu Pro Ala Leu Glu Lys Gly Ser

1 5 10 15

Val Trp Leu Val Gly Ala Gly Pro Gly Asp Pro Gly Leu Leu Thr Leu

20 25 30

His Ala Ala Asn Ala Leu Arg Gln Ala Asp Val Ile Val His Asp Ala

35 40 45

Leu Val Asn Glu Asp Cys Leu Lys Leu Ala Arg Pro Gly Ala Val Leu

50 55 60

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

65 70 75 80

Ile Ser Leu Arg Leu Val Glu Leu Ala Arg Ala Gly Asn Arg Val Leu

85 90 95

Arg Leu Lys Gly Gly Asp Pro Phe Val Phe Gly Arg Gly Gly Glu Glu

100 105 110

Ala Leu Thr Leu Val Glu His Gln Val Pro Phe Arg Ile Val Pro Gly

115 120 125

Ile Thr Ala Gly Ile Gly Gly Leu Ala Tyr Ala Gly Ile Pro Val Thr

130 135 140

His Arg Glu Val Asn His Ala Val Thr Phe Leu Thr Gly His Asp Ser

145 150 155 160

Ser Gly Leu Val Pro Asp Arg Ile Asn Trp Gln Gly Ile Ala Ser Gly

165 170 175

Ser Pro Val Ile Val Met Tyr Met Ala Met Lys His Ile Gly Ala Ile

180 185 190

Thr Ala Asn Leu Ile Ala Gly Gly Arg Ser Pro Asp Glu Pro Val Ala

195 200 205

Phe Val Cys Asn Ala Ala Thr Pro Gln Gln Ala Val Leu Glu Thr Thr

210 215 220

Leu Ala Arg Ala Glu Ala Asp Val Ala Ala Ala Gly Leu Glu Pro Pro

225 230 235 240

Ala Ile Val Val Val Gly Glu Val Val Arg Leu Arg Ala Ala Leu Asp

245 250 255

Trp Ile Gly Ala Leu Asp Gly Arg Lys Leu Ala Ala Asp Pro Phe Ala

260 265 270

Asn Arg Ile Leu Arg Asn Pro Ala

275 280

ATGAGCGGAT TGCTGATTGC CGCACCCGCG TCCGGCTCCG GCAAGACGAC GGTGACGCTC 60

GGGCTGATGC GCGCCCTGAA GAGGCGCGGC GTGGCGATCG CGCCCGGCAA GGCGGGGCCG 120

GACTATATCG ATCCCGCTTT CCACGCGGCA GCGACCGGCG AGCCCTGCTT CAACTACGAC 180

CCCTGGGCGA TGCGCCCGGA ACTGCTGCTT GCCAATGCGT CGCATGTGGC CTCCGGCGGG 240

CGCACATTGA TCGTCGAGGC GATGATGGGA CTGCATGACG GTGCTGCCGA CGGCTCGGGA 300

ACGCCAGCGG ACCTCGCCGC GACGCTGAAC CTTGCGGTCA TTCTGGTGGT CGATTGCGCC 360

CGCATGTCCC AGTCGGTTGC CGCCCTCGTG CGCGGCTATG CGGATCATCG CGACGATATC 420

CGGGTGGTTG GCGTCATCCT CAACAAGGTC GGCAGCGATC GGCATGAAAT GATGCTGCGC 480

GATGCGCTCG GCAAGGTGCG CATGCCTGTC TTCGGCGTGC TCCGGCAGGA CAGCGCATTG 540

CAACTGCCGG AGCGCCATCT CGGGCTCGTG CAGGCGGGCG AACACTCAGC GCTTGAGGGC 600

TTCATCGAGG CGGCGGCCGC GCGGGTCGAG GCTGCCTGCG ATCTCGACGC CATCCGCCTG 660

ATCGCGACGA TTTTCCCGCA GGTGCCCGCG GCGGCCGATG CCGAGCGTTT GCGGCCGCTC 720

GGTCAGCGCA TCGCGGTCGC GCGCGATATC GCCTTTGCCT TCTGCTACGA GCACCTGCTT 780

TACGGCTGGC GGCAAGGCGG CGCGGAGATT TCCTTCTTCT CGCCGCTCGC CGACGAGGGG 840

CCGGATGCGG CAGCCGATGC CGTCTATCTT CCGGGGGGTT ATCCGGAGCT GCATGCGGGG 900

CAGCTGAGCG CCGCCGCCCG ATTCCGTTCC GGCATGCATT CCGCGGCGGA ACGCGGCGCC 960

CGCATCTTCG GCGAGTGCGG CGGCTATATG GTGCTCGGCG AAGGGCTTGT CGCTGCCGAT 1020

GGCACACGCT ACGACATGCT CGGCCTGCTG CCGCTCGTAA CCAGTTTTGC CGAGCGCAGG 1080

CGGCACCTCG GCTATCGCCG CGTCGTGCCT GTCGACAACG CCTTCTTCGA TGGACCCATG 1140

ACGGCGCACG AATTCCACTA TGCGACCATC GTCGCCGAAG GGGCGGCCGA TCGGCTGTTT 1200

GCGGTCAGCG ACGCCGCCGG CGAGGATCTC GGCCAGGCGG GCCTCCGGCG CGGCCCTGTC 1260

GCCGGTTCCT TCATGCATCT GATCGACGTC GCAGGTGCTG CATGA 1305

Met Ser Gly Leu Leu Ile Ala Ala Pro Ala Ser Gly Ser Gly Lys Thr

1 5 10 15

Thr Val Thr Leu Gly Leu Met Arg Ala Leu Lys Arg Arg Gly Val Ala

20 25 30

Ile Ala Pro Gly Lys Ala Gly Pro Asp Tyr Ile Asp Pro Ala Phe His

35 40 45

Ala Ala Ala Thr Gly Glu Pro Cys Phe Asn Tyr Asp Pro Trp Ala Met

50 55 60

Arg Pro Glu Leu Leu Leu Ala Asn Ala Ser His Val Ala Ser Gly Gly

65 70 75 80

Arg Thr Leu Ile Val Glu Ala Met Met Gly Leu His Asp Gly Ala Ala

85 90 95

Asp Gly Ser Gly Thr Pro Ala Asp Leu Ala Ala Thr Leu Asn Leu Ala

100 105 110

Val Ile Leu Val Val Asp Cys Ala Arg Met Ser Gln Ser Val Ala Ala

115 120 125

Leu Val Arg Gly Tyr Ala Asp His Arg Asp Asp Ile Arg Val Val Gly

130 135 140

Val Ile Leu Asn Lys Val Gly Ser Asp Arg His Glu Met Met Leu Arg

145 150 155 160

Asp Ala Leu Gly Lys Val Arg Met Pro Val Phe Gly Val Leu Arg Gln

165 170 175

Asp Ser Ala Leu Gln Leu Pro Glu Arg His Leu Gly Leu Val Gln Ala

180 185 190

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

195 200 205

Val Glu Ala Ala Cys Asp Leu Asp Ala Ile Arg Leu Ile Ala Thr Ile

210 215 220

Phe Pro Gln Val Pro Ala Ala Ala Asp Ala Glu Arg Leu Arg Pro Leu

225 230 235 240

Gly Gln Arg Ile Ala Val Ala Arg Asp Ile Ala Phe Ala Phe Cys Tyr

245 250 255

Glu His Leu Leu Tyr Gly Trp Arg Gln Gly Gly Ala Glu Ile Ser Phe

260 265 270

Phe Ser Pro Leu Ala Asp Glu Gly Pro Asp Ala Ala Ala Asp Ala Val

275 280 285

Tyr Leu Pro Gly Gly Tyr Pro Glu Leu His Ala Gly Gln Leu Ser Ala

290 295 300

Ala Ala Arg Phe Arg Ser Gly Met His Ser Ala Ala Glu Arg Gly Ala

305 310 315 320

Arg Ile Phe Gly Glu Cys Gly Gly Tyr Met Val Leu Gly Glu Gly Leu

325 330 335

Val Ala Ala Asp Gly Thr Arg Tyr Asp Met Leu Gly Leu Leu Pro Leu

340 345 350

Val Thr Ser Phe Ala Glu Arg Arg Arg His Leu Gly Tyr Arg Arg Val

355 360 365

Val Pro Val Asp Asn Ala Phe Phe Asp Gly Pro Met Thr Ala His Glu

370 375 380

Phe His Tyr Ala Thr Ile Val Ala Glu Gly Ala Ala Asp Arg Leu Phe

385 390 395 400

Ala Val Ser Asp Ala Ala Gly Glu Asp Leu Gly Gln Ala Gly Leu Arg

405 410 415

Arg Gly Pro Val Ala Gly Ser Phe Met His Leu Ile Asp Val Ala Gly

420 425 430

Ala Ala

ATGAGCGCAC CGATCGTTCA TGGTGGCGGC ATCACCGAGG CCGCAGCGCG CTATGGCGGC 60

CGGCCTGAAG ACTGGCTCGA TCTGTCGACC GGCATCAATC CATGCCCCGT CGCCTTGCCC 120

GCGGTCCCTG AGCGCGCCTG GCACCGGCTG CCGGATCGGC AGACGGTAGA TGATGCGCGG 180

AGCGCCGCCG CCGACTACTA CCGCACCAAC GGCGTGCTGC CTTTGCCGGT GCCGGGCACC 240

CAGTCGGTGA TCCAGCTCCT GCCACGTCTT GCTCCGGCCA ACAGGCACGT CGCGATTTTC 300

GGGCCGACCT ATGGCGAGTA TGCCCGCGTG CTTGAAGCGG CCGGCTTTGC TGTCGATCGC 360

GTCGCGGATG CCGACGCGCT CACGGCCGAA CATGGGCTTG TCATCGTCGT CAACCCCAAC 420

AACCCGACCG GCCGCGCCTT GGCGCCGGCG GAGCTTCTGG CGATCGCCGC AAGGCAGAAG 480

GCGAGCGGCG GACTGCTGCT GGTCGATGAG GCCTTCGGCG ATCTTGAGCC GCAACTGAGT 540

GTCGCTGGTC ACGCGTCAGG GCAAGGCAAC CTCATCGTCT TCCGCTCCTT CGGCAAGTTC 600

TTCGGCCTTG CGGGCCTGCG CCTCGGCTTC GTCGTTGCGA CCGAGCCAGT GCTTGCATCC 660

TTTGCCGATT GGCTCGGTCC CTGGGCTGTC TCCGGCCCGG CGTTGACGAT CTCGAAAGCG 720

CTGATGCAGG GCGATACGAA GGCGATCGCG GCGGGCATCC TCGAGCGTCG CGCCGGCCTC 780

GATGCGGCTC TCGATGGGGC AGGGCTCAAC CGTATCGGCG GCACGGGGCT ATTCGTGCTG 840

GTCGAGCATC CCAGGGCAGC TCTGCTGCAG GAGCGGCTCT GCGAGGCCCA TATTCTCACG 900

CGCAAGTTCG ACTATGCCCC GACCTGGCTC AGGGTCGGTC TTGCGCCTGA CGCGGCTGGT 960

GACCGACGGC TGGCGGACGC GCTTGCCCGC ATGGAGCTCT GA 1002

Met Ser Ala Pro Ile Val His Gly Gly Gly Ile Thr Glu Ala Ala Ala

1 5 10 15

Arg Tyr Gly Gly Arg Pro Glu Asp Trp Leu Asp Leu Ser Thr Gly Ile

20 25 30

Asn Pro Cys Pro Val Ala Leu Pro Ala Val Pro Glu Arg Ala Trp His

35 40 45

Arg Leu Pro Asp Arg Gln Thr Val Asp Asp Ala Arg Ser Ala Ala Ala

50 55 60

Asp Tyr Tyr Arg Thr Asn Gly Val Leu Pro Leu Pro Val Pro Gly Thr

65 70 75 80

Gln Ser Val Ile Gln Leu Leu Pro Arg Leu Ala Pro Ala Asn Arg His

85 90 95

Val Ala Ile Phe Gly Pro Thr Tyr Gly Glu Tyr Ala Arg Val Leu Glu

100 105 110

Ala Ala Gly Phe Ala Val Asp Arg Val Ala Asp Ala Asp Ala Leu Thr

115 120 125

Ala Glu His Gly Leu Val Ile Val Val Asn Pro Asn Asn Pro Thr Gly

130 135 140

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

145 150 155 160

Ala Ser Gly Gly Leu Leu Leu Val Asp Glu Ala Phe Gly Asp Leu Glu

165 170 175

Pro Gln Leu Ser Val Ala Gly His Ala Ser Gly Gln Gly Asn Leu Ile

180 185 190

Val Phe Arg Ser Phe Gly Lys Phe Phe Gly Leu Ala Gly Leu Arg Leu

195 200 205

Gly Phe Val Val Ala Thr Glu Pro Val Leu Ala Ser Phe Ala Asp Trp

210 215 220

Leu Gly Pro Trp Ala Val Ser Gly Pro Ala Leu Thr Ile Ser Lys Ala

225 230 235 240

Leu Met Gln Gly Asp Thr Lys Ala Ile Ala Ala Gly Ile Leu Glu Arg

245 250 255

Arg Ala Gly Leu Asp Ala Ala Leu Asp Gly Ala Gly Leu Asn Arg Ile

260 265 270

Gly Gly Thr Gly Leu Phe Val Leu Val Glu His Pro Arg Ala Ala Leu

275 280 285

Leu Gln Glu Arg Leu Cys Glu Ala His Ile Leu Thr Arg Lys Phe Asp

290 295 300

Tyr Ala Pro Thr Trp Leu Arg Val Gly Leu Ala Pro Asp Ala Ala Gly

305 310 315 320

Asp Arg Arg Leu Ala Asp Ala Leu Ala Arg Met Glu Leu

GTGTCGGAGA CGATCCTGCT CATTCTCGCG CTGGCGCTGG TGATCGACCG CGTTGTCGGC 60

GATCCGGACT GGCTCTGGGC GCGCGTGCCG CATCCGGTCG TGTTTTTCGG CAAGGCCATC 120

GGCTTTTTCG ACGCGCGGCT GAACCGGGAG GACCTCGAGG ATAGCGCGCG CAAATTTCGT 180

GGCGTCGTCG CGATCCTTTT GTTGCTTGGC ATCAGCGCCT GGTTCGGCCA TCTGCTGCAT 240

CGCCTGTTCG CCGTCCTCGG ACCGCTCGGC TTTCTGCTCG AGGCGGTTCT GGTCGCGGTC 300

TTCCTGGCAC AGAAGAGCCT CGCCGATCAC GTGCGTCGCG TGGCCGGGGG CTTGCGACAG 360

GGCGGGCTGG AAGGCGGGCG TGCCGCCGTG TCGATGATCG TTGGTCGCGA TCCAAAGACG 420

CTCGACGAGC CGGCGGTCTG CCGTGCCGCG ATCGAAAGCC TTGCCGAGAA TTTCTCCGAC 480

GGCGTCGTGG CGCCGGCCTT CTGGTACGCG GTTGCCGGCC TGCCGGGGCT TCTTGCCTAC 540

AAGATGCTGA ACACCGCCGA TTCGATGATC GGCCACAAGT CGCCGAAATA TCTGCACTTC 600

GGCTGGGCCT CGGCCCGACT CGACGATCTC GCCAACCTGC CGGCAGCGAG GCTCTCGATC 660

CTTTTGATCT CAGCCGGTGC GCTGATCCAT CGTGGCGCCA GCGCCGCCAA GGATGCGCTG 720

ACCGTGGCCC TTCGCGACCA TGGCCTGCAC CGCTCGCCGA ACTCCGGCTG GCCGGAAGCG 780

GCCATGGCCG GCGCGCTCGA TCTGCAGCTT GCCGGTCCGC GGATCTATGG CGGCGTCAAG 840

GTCAGCGAAC CTATGATCAA CGGTCCGGGC CGAGCGGTTG CAACAAGCGA AGACATCGAC 900

GCCGGTATTG CTGTATTTTA TGGCGCCTGT ACGGTCATGG CCGGGTTTGT TCTTGCAATC 960

GCAATGATTT GA 972

Met Ser Glu Thr Ile Leu Leu Ile Leu Ala Leu Ala Leu Val Ile Asp

1 5 10 15

Arg Val Val Gly Asp Pro Asp Trp Leu Trp Ala Arg Val Pro His Pro

20 25 30

Val Val Phe Phe Gly Lys Ala Ile Gly Phe Phe Asp Ala Arg Leu Asn

35 40 45

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

50 55 60

Ile Leu Leu Leu Leu Gly Ile Ser Ala Trp Phe Gly His Leu Leu His

65 70 75 80

Arg Leu Phe Ala Val Leu Gly Pro Leu Gly Phe Leu Leu Glu Ala Val

85 90 95

Leu Val Ala Val Phe Leu Ala Gln Lys Ser Leu Ala Asp His Val Arg

100 105 110

Arg Val Ala Gly Gly Leu Arg Gln Gly Gly Leu Glu Gly Gly Arg Ala

115 120 125

Ala Val Ser Met Ile Val Gly Arg Asp Pro Lys Thr Leu Asp Glu Pro

130 135 140

Ala Val Cys Arg Ala Ala Ile Glu Ser Leu Ala Glu Asn Phe Ser Asp

145 150 155 160

Gly Val Val Ala Pro Ala Phe Trp Tyr Ala Val Ala Gly Leu Pro Gly

165 170 175

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

180 185 190

Lys Ser Pro Lys Tyr Leu His Phe Gly Trp Ala Ser Ala Arg Leu Asp

195 200 205

Asp Leu Ala Asn Leu Pro Ala Ala Arg Leu Ser Ile Leu Leu Ile Ser

210 215 220

Ala Gly Ala Leu Ile His Arg Gly Ala Ser Ala Ala Lys Asp Ala Leu

225 230 235 240

Thr Val Ala Leu Arg Asp His Gly Leu His Arg Ser Pro Asn Ser Gly

245 250 255

Trp Pro Glu Ala Ala Met Ala Gly Ala Leu Asp Leu Gln Leu Ala Gly

260 265 270

Pro Arg Ile Tyr Gly Gly Val Lys Val Ser Glu Pro Met Ile Asn Gly

275 280 285

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

290 295 300

Val Phe Tyr Gly Ala Cys Thr Val Met Ala Gly Phe Val Leu Ala Ile

305 310 315 320

Ala Met Ile

ATGCCATCGG GCCAACACTC TGCACAGACG ACGAAAGCAG GAGCCGGGCT GGTGCTCGGG 60

CTCGGCTGCG AGCGTCGCAC GCCGGCCGAA GAGGTGATCG CCCTTGCCGA GCGTGCGCTT 120

GCCGATGCCG GTGTTGCGCC CGGCGATCTG CGGCTGGTCG CCTCGCTCGA TGCTCGCGCC 180

GAGGAGCCGG CGATCCTGGC GGCCGCTCAG CATTTCGCGG TTCCGGCCGC GTTCTACGAT 240

GCCGCCACGC TCGAAGCCGA AGCTTCCCGG CTCGCCAACC CGTCCGAGAT CGTCTTTGCC 300

TACACGGGTT GTCATGGCGT TGCCGAGGGT GCAGCGCTCG TCGGCGCCGG TCGCGAAGCC 360

GTGCTGATTG TGCAGAAGAT CGTCTCCGCC CATGCGACGG CCGCACTTGC CGGGCCGGCG 420

ACCTTGCGCG CCGAAAAGCG CATCCAGGCG GCGGAGGCTG TCTGA 465

Met Pro Ser Gly Gln His Ser Ala Gln Thr Thr Lys Ala Gly Ala Gly

1 5 10 15

Leu Val Leu Gly Leu Gly Cys Glu Arg Arg Thr Pro Ala Glu Glu Val

20 25 30

Ile Ala Leu Ala Glu Arg Ala Leu Ala Asp Ala Gly Val Ala Pro Gly

35 40 45

Asp Leu Arg Leu Val Ala Ser Leu Asp Ala Arg Ala Glu Glu Pro Ala

50 55 60

Ile Leu Ala Ala Ala Gln His Phe Ala Val Pro Ala Ala Phe Tyr Asp

65 70 75 80

Ala Ala Thr Leu Glu Ala Glu Ala Ser Arg Leu Ala Asn Pro Ser Glu

85 90 95

Ile Val Phe Ala Tyr Thr Gly Cys His Gly Val Ala Glu Gly Ala Ala

100 105 110

Leu Val Gly Ala Gly Arg Glu Ala Val Leu Ile Val Gln Lys Ile Val

115 120 125

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

130 135 140

Glu Lys Arg Ile Gln Ala Ala Glu Ala Val

145 150

ATGGCGGAGG CGGGCATGCG CAAAATTCTG ATCATCGGCA TCGGTTCGGG CAATCCCGAA 60

CACATGACCG TGCAGGCGAT CAACGCGCTG AACTGCGCCG ACGTGCTCTT TATCCCGACC 120

AAGGGAGCGA AGAAGACCGA GCTTGCCGAA GTGCGCCGCG ACATCTGCGC CCGCTACGTC 180

ACGCGCAAGG ACAGCCGCAC CGTCGAGTTC GCGGTGCCCG TGCGGCGCAC CGAAGGCGTC 240

AGCTATGACG GCAGCGTCGA TGACTGGCAC GCCCAGATCG CTGGGATTTA CGAAGCGCTT 300

CTATCGAAGG AGTTGGGCGA AGAGGGAACT GGCGCGTTTC TCGTCTGGGG CGACCCGATG 360

CTCTATGACA GCACCATTCG CATCGTCGAG CGGGTCAAGG CACGCGGTGA GGTCGCCTTC 420

GCCTACGACG TCATTCCCGG GATCACCAGT CTGCAGGCGC TTTGCGCCAG CCACCGCATT 480

CCGCTGAACC TCGTCGGCAA GCCGGTGGAG ATCACCACGG GGCGTCGGCT GCACGAAAGC 540

TTTCCCGAGA AGAGCCAGAC CTCGGTCGTC ATGCTCGATG GCGAACAGGC GTTTCAGCGG 600

GTCGAGGACC CGGAGGCGGA GATCTATTGG GGCGCCTATC TCGGCACGCG GGATGAGATC 660

GTCATTTCCG GCCGCGTGGC TGAGGTGAAG GACCGGATCC TTGAAACGCG GGCGGCGGCG 720

CGCGCGAAGA TGGGATGGAT CATGGACATC TATCTCCTGC GCAAGGGCGC CGACTTCGAC 780

GAGTGA 786

Met Ala Glu Ala Gly Met Arg Lys Ile Leu Ile Ile Gly Ile Gly Ser

1 5 10 15

Gly Asn Pro Glu His Met Thr Val Gln Ala Ile Asn Ala Leu Asn Cys

20 25 30

Ala Asp Val Leu Phe Ile Pro Thr Lys Gly Ala Lys Lys Thr Glu Leu

35 40 45

Ala Glu Val Arg Arg Asp Ile Cys Ala Arg Tyr Val Thr Arg Lys Asp

50 55 60

Ser Arg Thr Val Glu Phe Ala Val Pro Val Arg Arg Thr Glu Gly Val

65 70 75 80

Ser Tyr Asp Gly Ser Val Asp Asp Trp His Ala Gln Ile Ala Gly Ile

85 90 95

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

100 105 110

Phe Leu Val Trp Gly Asp Pro Met Leu Tyr Asp Ser Thr Ile Arg Ile

115 120 125

Val Glu Arg Val Lys Ala Arg Gly Glu Val Ala Phe Ala Tyr Asp Val

130 135 140

Ile Pro Gly Ile Thr Ser Leu Gln Ala Leu Cys Ala Ser His Arg Ile

145 150 155 160

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

165 170 175

Leu His Glu Ser Phe Pro Glu Lys Ser Gln Thr Ser Val Val Met Leu

180 185 190

Asp Gly Glu Gln Ala Phe Gln Arg Val Glu Asp Pro Glu Ala Glu Ile

195 200 205

Tyr Trp Gly Ala Tyr Leu Gly Thr Arg Asp Glu Ile Val Ile Ser Gly

210 215 220

Arg Val Ala Glu Val Lys Asp Arg Ile Leu Glu Thr Arg Ala Ala Ala

225 230 235 240

Arg Ala Lys Met Gly Trp Ile Met Asp Ile Tyr Leu Leu Arg Lys Gly

245 250 255

Ala Asp Phe Asp Glu

260

ATGACGGATT TGATGACCAG CTGCGCCCTT CCATTGACCG GAGATGCCGG CACCGTCGCT 60

TCGATGCGCC GCGGCGCCTG CCCGTCCTTG GCAGAGCCGA TGCAGACCGG CGACGGCCTG 120

CTCGTGAGGG TGAGGCCAAC GGATGACAGC CTGACGCTGC CGAAGGTCAT TGCCCTTGCC 180

ACGGCTGCCG AGCGCTTCGG CAATGGCATC ATCGAGATTA CCGCGCGCGG AAACCTGCAG 240

CTTCGCGGCC TGAGCGCGGC TTCGGTGCCA AGGCTGGCGC AGGCGATCGG CGATGCGGAG 300

ATCGCCATTG CCGAGGGGCT CGCGATCGAG GTGCCGCCCC TGGCCGGCAT CGACCCGGAC 360

GAGATCGCCG ATCCGCGGCC GATTGCCACT GAGCTTCGTG AAGCGTTGGA TGTGCGCCAG 420

GTGCCGTTGA AGCTTGCACC CAAATTATCC GTCGTCATCG ATAGCGGTGG CCGGTTTGGT 480

CTCGGCGCTG TCGTCGCCGA CATTCGCCTT CAGGCGGTTT CGACTGTCGC GGGGGTGGCC 540

TGGGTGCTGT CGCTTGGCGG CACGTCAACG AAGGCATCGA GCGTCGGGAC GTTGGCCGGC 600

AACGCGGTCG TGCCGGCCCT GATCACCATT CTCGAGAAAC TGGCGAGCCT GGGCACGACG 660

ATGCGCGGGC GCGATCTGGA CCCGTCGGAA ATCCGCGCGC TCTGTCGCTG TGAGACATCG 720

TCCGAACGCC CGGCCGCTCC GCGTTCGGCC GCAATACCCG GCATTCATGC GCTGGGTAAC 780

GCCGACACCG TTCTCGGCCT CGGTCTGGCC TTTGCTCAGG TGGAGGCCGC CGCGCTGGCA 840

TCCTACCTGC ATCAGGTCCA GGCGCTTGGC GCCAATGCGA TCCGGCTTGC GCCCGGGCAC 900

GCCTTCTTCG TCCTCGGCCT TTGCCCCGAG ACCGCGGCTG TGGCGCAGAG CCTGGCAGCG 960

TCACACGGTT TTCGCATTGC CGAGCAGGAT CCGCGCAATG CGATCGCCAC CTGCGCCGGC 1020

AGCAAGGGTT GCGCCTCGGC GTGGATGGAA ACCAAGGGCA TGGCCGAGCG CCTCGTCGAG 1080

ACGGCGCCGG AATTGCTCGA CGGGTCGCTC ACCGTGCATC TCTCCGGCTG CGCCAAGGGC 1140

TGCGCCCGGC CGAAGCCGTC CGAACTGACG CTTGTCGGTG CGCCATCAGG ATACGGGCTT 1200

GTCGTAAATG GGGCTGCCAA TGGCTTGCCA AGCGCCTACA CCGATGAGAA TGGAATGGGA 1260

TCCGCCCTTG CCCGGCTCGG CCGGCTGGTG CGGCAAAACA AAGACGCTGG CGAATCGGCG 1320

CAGTCCTGTC TTACACGGCT CGGAGCTGCG CGCGTCTCGG CAGCGTTCGA ACAGGGATAG 1380

Met Thr Asp Leu Met Thr Ser Cys Ala Leu Pro Leu Thr Gly Asp Ala

1 5 10 15

Gly Thr Val Ala Ser Met Arg Arg Gly Ala Cys Pro Ser Leu Ala Glu

20 25 30

Pro Met Gln Thr Gly Asp Gly Leu Leu Val Arg Val Arg Pro Thr Asp

35 40 45

Asp Ser Leu Thr Leu Pro Lys Val Ile Ala Leu Ala Thr Ala Ala Glu

50 55 60

Arg Phe Gly Asn Gly Ile Ile Glu Ile Thr Ala Arg Gly Asn Leu Gln

65 70 75 80

Leu Arg Gly Leu Ser Ala Ala Ser Val Pro Arg Leu Ala Gln Ala Ile

85 90 95

Gly Asp Ala Glu Ile Ala Ile Ala Glu Gly Leu Ala Ile Glu Val Pro

100 105 110

Pro Leu Ala Gly Ile Asp Pro Asp Glu Ile Ala Asp Pro Arg Pro Ile

115 120 125

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

130 135 140

Leu Ala Pro Lys Leu Ser Val Val Ile Asp Ser Gly Gly Arg Phe Gly

145 150 155 160

Leu Gly Ala Val Val Ala Asp Ile Arg Leu Gln Ala Val Ser Thr Val

165 170 175

Ala Gly Val Ala Trp Val Leu Ser Leu Gly Gly Thr Ser Thr Lys Ala

180 185 190

Ser Ser Val Gly Thr Leu Ala Gly Asn Ala Val Val Pro Ala Leu Ile

195 200 205

Thr Ile Leu Glu Lys Leu Ala Ser Leu Gly Thr Thr Met Arg Gly Arg

210 215 220

Asp Leu Asp Pro Ser Glu Ile Arg Ala Leu Cys Arg Cys Glu Thr Ser

225 230 235 240

Ser Glu Arg Pro Ala Ala Pro Arg Ser Ala Ala Ile Pro Gly Ile His

245 250 255

Ala Leu Gly Asn Ala Asp Thr Val Leu Gly Leu Gly Leu Ala Phe Ala

260 265 270

Gln Val Glu Ala Ala Ala Leu Ala Ser Tyr Leu His Gln Val Gln Ala

275 280 285

Leu Gly Ala Asn Ala Ile Arg Leu Ala Pro Gly His Ala Phe Phe Val

290 295 300

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

305 310 315 320

Ser His Gly Phe Arg Ile Ala Glu Gln Asp Pro Arg Asn Ala Ile Ala

325 330 335

Thr Cys Ala Gly Ser Lys Gly Cys Ala Ser Ala Trp Met Glu Thr Lys

340 345 350

Gly Met Ala Glu Arg Leu Val Glu Thr Ala Pro Glu Leu Leu Asp Gly

355 360 365

Ser Leu Thr Val His Leu Ser Gly Cys Ala Lys Gly Cys Ala Arg Pro

370 375 380

Lys Pro Ser Glu Leu Thr Leu Val Gly Ala Pro Ser Gly Tyr Gly Leu

385 390 395 400

Val Val Asn Gly Ala Ala Asn Gly Leu Pro Ser Ala Tyr Thr Asp Glu

405 410 415

Asn Gly Met Gly Ser Ala Leu Ala Arg Leu Gly Arg Leu Val Arg Gln

420 425 430

Asn Lys Asp Ala Gly Glu Ser Ala Gln Ser Cys Leu Thr Arg Leu Gly

435 440 445

Ala Ala Arg Val Ser Ala Ala Phe Glu Gln Gly

450 455

ATGCCTGAGT ATGATTACAT TCGCGATGGC AACGCCATCT ACGAGCGTTC CTTCGCCATC 60

ATCCGCGCCG AGGCCGATCT GTCGCGCTTC TCCGAAGAGG AAGCGGATCT GGCTGTGCGC 120

ATGGTGCACG CCTGCGGTTC CGTCGAGGCG ACCAGGCAGT TCGTGTTTTC TCCCGATTTC 180

GTAAGCTCGG CCCGTGCGGC GCTGAAAGCC GGTGCGCCGA TCCTCTGCGA TGCCGAGATG 240

GTTGCGCACG GTGTCACCCG CGCCCGTCTG CCGGCCGGCA ACGAGGTGAT CTGCACGCTG 300

CGCGATCCTC GCACGCCCGC ACTTGCGGCC GAGATCGGCA ACACCCGCTC CGCCGCAGCC 360

CTGAAGCTCT GGAGCGAGCG GCTGGCCGGT TCGGTGGTCG CGATCGGCAA CGCGCCGACG 420

GCGTTGTTCT TCCTCTTGGA AATGCTGCGC GACGGCGCGC CGAAGCCGGC GGCAATCCTC 480

GGCATGCCCG TCGGTTTCGT CGGTGCGGCG GAATCGAAGG ATGCGCTGGC CGAGAACTCC 540

TATGGCGTTC CCTTCGCCAT CGTGCGCGGC CGCCTCGGCG GGAGTGCCAT GACGGCGGCA 600

GCGCTTAACT CGCTCGCGAG GCCGGGCCTG TGA 633

Met Pro Glu Tyr Asp Tyr Ile Arg Asp Gly Asn Ala Ile Tyr Glu Arg

1 5 10 15

Ser Phe Ala Ile Ile Arg Ala Glu Ala Asp Leu Ser Arg Phe Ser Glu

20 25 30

Glu Glu Ala Asp Leu Ala Val Arg Met Val His Ala Cys Gly Ser Val

35 40 45

Glu Ala Thr Arg Gln Phe Val Phe Ser Pro Asp Phe Val Ser Ser Ala

50 55 60

Arg Ala Ala Leu Lys Ala Gly Ala Pro Ile Leu Cys Asp Ala Glu Met

65 70 75 80

Val Ala His Gly Val Thr Arg Ala Arg Leu Pro Ala Gly Asn Glu Val

85 90 95

Ile Cys Thr Leu Arg Asp Pro Arg Thr Pro Ala Leu Ala Ala Glu Ile

100 105 110

Gly Asn Thr Arg Ser Ala Ala Ala Leu Lys Leu Trp Ser Glu Arg Leu

115 120 125

Ala Gly Ser Val Val Ala Ile Gly Asn Ala Pro Thr Ala Leu Phe Phe

130 135 140

Leu Leu Glu Met Leu Arg Asp Gly Ala Pro Lys Pro Ala Ala Ile Leu

145 150 155 160

Gly Met Pro Val Gly Phe Val Gly Ala Ala Glu Ser Lys Asp Ala Leu

165 170 175

Ala Glu Asn Ser Tyr Gly Val Pro Phe Ala Ile Val Arg Gly Arg Leu

180 185 190

Gly Gly Ser Ala Met Thr Ala Ala Ala Leu Asn Ser Leu Ala Arg Pro

195 200 205

Gly Leu

210

GTGAGCGGCG TCGGCGTGGG GCGCCTGATC GGTGTTGGGA CCGGCCCCGG TGATCCGGAA 60

CTTTTGACGG TCAAGGCGGT GAAGGCGCTC GGGCAAGCCG ATGTGCTTGC CTATTTCGCC 120

AAGGCCGGGC GAAGCGGTAA CGGCCGCGCG GTGGTCGAGG GTCTGCTGAA GCCCGATCTT 180

GTCGAGCTGC CGCTATACTA TCCGGTGACG ACCGAAATCG ACAAGGACGA TGGCGCCTAC 240

AAGACCCAGA TCACCGACTT CTACAATGCG TCGGCCGAAG CGGTAGCGGC GCATCTTGCC 300

GCCGGGCGCA CGGTCGCCGT GCTCAGTGAA GGCGACCCGC TGTTCTATGG TTCCTACATG 360

CATCTGCATG TGCGGCTCGC CAATCGTTTC CCGGTCGAGG TGATCCCCGG CATTACCGCC 420

ATGTCCGGCT GTTGGTCGCT TGCCGGCCTG CCGCTGGTGC AGGGCGACGA CGTGCTCTCG 480

GTGCTTCCGG GCACCATGGC CGAGGCCGAG CTCGGCCGCA GGCTTGCGGA TACCGAAGCC 540

GCCGTGATCA TGAAGGTCGG GCGCAATTTG CCGAAGATCC GTCGGGCGCT CGCTGCCTCC 600

GGCCGTCTCG ACCAGGCCGT CTATGTCGAA CGCGGCACGA TGAAGAACGC GGCGATGACG 660

GCTCTTGCGG AAAAGGCCGA CGACGAGGCG CCCTATTTCT CGCTGGTGCT CGTTCCCGGC 720

TGGAAGGACC GACCATGA 738

Met Ser Gly Val Gly Val Gly Arg Leu Ile Gly Val Gly Thr Gly Pro

1 5 10 15

Gly Asp Pro Glu Leu Leu Thr Val Lys Ala Val Lys Ala Leu Gly Gln

20 25 30

Ala Asp Val Leu Ala Tyr Phe Ala Lys Ala Gly Arg Ser Gly Asn Gly

35 40 45

Arg Ala Val Val Glu Gly Leu Leu Lys Pro Asp Leu Val Glu Leu Pro

50 55 60

Leu Tyr Tyr Pro Val Thr Thr Glu Ile Asp Lys Asp Asp Gly Ala Tyr

65 70 75 80

Lys Thr Gln Ile Thr Asp Phe Tyr Asn Ala Ser Ala Glu Ala Val Ala

85 90 95

Ala His Leu Ala Ala Gly Arg Thr Val Ala Val Leu Ser Glu Gly Asp

100 105 110

Pro Leu Phe Tyr Gly Ser Tyr Met His Leu His Val Arg Leu Ala Asn

115 120 125

Arg Phe Pro Val Glu Val Ile Pro Gly Ile Thr Ala Met Ser Gly Cys

130 135 140

Trp Ser Leu Ala Gly Leu Pro Leu Val Gln Gly Asp Asp Val Leu Ser

145 150 155 160

Val Leu Pro Gly Thr Met Ala Glu Ala Glu Leu Gly Arg Arg Leu Ala

165 170 175

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

180 185 190

Ile Arg Arg Ala Leu Ala Ala Ser Gly Arg Leu Asp Gln Ala Val Tyr

195 200 205

Val Glu Arg Gly Thr Met Lys Asn Ala Ala Met Thr Ala Leu Ala Glu

210 215 220

Lys Ala Asp Asp Glu Ala Pro Tyr Phe Ser Leu Val Leu Val Pro Gly

225 230 235 240

Trp Lys Asp Arg Pro

ATGACCGGTA CGCTCTATGT CGTCGGTACC GGACCGGGCA GCGCCAAGCA GATGACGCCG 60

GAAACGGCGG AAGCCGTTGC GGCCGCTCAG GAGTTTTACG GCTACTTTCC CTATCTCGAC 120

CGGCTGAACC TCAGACCGGA TCAGATCCGT GTCGCCTCGG ACAACCGCGA GGAGCTCGAT 180

CGGGCACAGG TCGCGCTGAC GCGGGCTGCG GCAGGCGTGA AGGTCTGCAT GGTCTCCGGT 240

GGCGATCCCG GTGTCTTTGC CATGGCGGCC GCCGTCTGCG AGGCGATCGA CAAGGGACCG 300

GCGGAATGGA AGTCGGTTGA ACTGGTGATC ACGCCCGGCG TGACCGCGAT GCTCGCCGTT 360

GCCGCCCGCA TCGGCGCGCC GCTCGGTCAT GATTTCTGTG CGATCTCGCT TTCCGACAAT 420

CTGAAGCCCT GGGAAGTCAT CACCCGGCGT CTCAGGCTGG CGGCGGAAGC GGGCTTCGTC 480

ATTGCCCTCT ACAATCCGAT CAGCAAGGCG CGGCCCTGGC AGCTCGGTGA GGCCTTCGAG 540

CTTCTGCGCA GCGTTCTGCC GGCAAGCGTT CCGGTCATCT TCGGCCGTGC GGCCGGGCGG 600

CCGGACGAAC GGATCGCGGT GATGCCGCTC GGCGAGGCCG ATGCCAACCG CGCCGACATG 660

GCGACCTGCG TCATCATCGG CTCGCCGGAG ACGCGCATCG TCGAGCGCGA CGGCCAACCC 720

GATCTCGTCT ACACACCGCG CTTCTATGCA GGGGCGAGCC AGTG 764

Met Thr Gly Thr Leu Tyr Val Val Gly Thr Gly Pro Gly Ser Ala Lys

1 5 10 15

Gln Met Thr Pro Glu Thr Ala Glu Ala Val Ala Ala Ala Gln Glu Phe

20 25 30

Tyr Gly Tyr Phe Pro Tyr Leu Asp Arg Leu Asn Leu Arg Pro Asp Gln

35 40 45

Ile Arg Val Ala Ser Asp Asn Arg Glu Glu Leu Asp Arg Ala Gln Val

50 55 60

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

65 70 75 80

Gly Asp Pro Gly Val Phe Ala Met Ala Ala Ala Val Cys Glu Ala Ile

85 90 95

Asp Lys Gly Pro Ala Glu Trp Lys Ser Val Glu Leu Val Ile Thr Pro

100 105 110

Gly Val Thr Ala Met Leu Ala Val Ala Ala Arg Ile Gly Ala Pro Leu

115 120 125

Gly His Asp Phe Cys Ala Ile Ser Leu Ser Asp Asn Leu Lys Pro Trp

130 135 140

Glu Val Ile Thr Arg Arg Leu Arg Leu Ala Ala Glu Ala Gly Phe Val

145 150 155 160

Ile Ala Leu Tyr Asn Pro Ile Ser Lys Ala Arg Pro Trp Gln Leu Gly

165 170 175

Glu Ala Phe Glu Leu Leu Arg Ser Val Leu Pro Ala Ser Val Pro Val

180 185 190

Ile Phe Gly Arg Ala Ala Gly Arg Pro Asp Glu Arg Ile Ala Val Met

195 200 205

Pro Leu Gly Glu Ala Asp Ala Asn Arg Ala Asp Met Ala Thr Cys Val

210 215 220

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

225 230 235 240

Asp Leu Val Tyr Thr Pro Arg Phe Tyr Ala Gly Ala Ser Gln

ATGGCGGGTT CGCTGTTCGA CACGTCAGCC ATGGAAAAAC CTCGTATTCT GATTCTGGGT 60

GGCACCACCG AGGCACGCGA ACTCGCGCGC CGCTTGGCCG AAGATGTCCG CTACGACACC 120

GCCATCTCGC TGGCCGGCCG CACCGCGGAC CCGCGGCCGC AGCCGGTCAA GACGCGCATC 180

GGCGGCTTTG GCGGCGCCGA TGGGCTGGCG CATTTCGTGC ATGACGAAAA CATCGCGCTG 240

CTGGTCGATG CGACGCACCC CTTTGCCGCA CGCATTTCGC ACAACGCCGC GGACGCAGCG 300

CAAAGAACCG GCGTTGCGCT TATCGCCCTC CGCCGACCGG AATGGGTGCC CCTGCCTGGC 360

GACCGCTGGA CTGCTGTCGA TAGCGTTGTC GAGGCCGTCA GCGCGCTCGG TGATCGGCGA 420

CGCCGCGTCT TCCTGGCGAT AGGTCGACAG GAAGCTTTCC ACTTCGAGGT CGCGCCGCAG 480

CACAGCTACG TCATCCGCAG CGTCGATCCG GTGACGCCGC CGCTTAATCT GCCCGACCAG 540

GAGGCGATCC TGGCGACCGG TCCCTTTGCG GAAGCCGACG AAGCCGCGTT GCTCAGGAGT 600

CGGCAGATCG ATGTGATCGT CGCCAAGAAC AGCGGTGGCA GCGCCACCTA CGGCAAGATT 660

GCCGCAGCGC GCCGGCTCGG CATCGAGGTG ATCATGGTCG AGCGGCGCAA GCCCGCGGAC 720

GTGCCGACGG TCGGCAGTTG CGACGAGGCA CTCAACCGCA TCGCTCACTG GCTCGCCCCT 780

GCATGA 786

Met Ala Gly Ser Leu Phe Asp Thr Ser Ala Met Glu Lys Pro Arg Ile

1 5 10 15

Leu Ile Leu Gly Gly Thr Thr Glu Ala Arg Glu Leu Ala Arg Arg Leu

20 25 30

Ala Glu Asp Val Arg Tyr Asp Thr Ala Ile Ser Leu Ala Gly Arg Thr

35 40 45

Ala Asp Pro Arg Pro Gln Pro Val Lys Thr Arg Ile Gly Gly Phe Gly

50 55 60

Gly Ala Asp Gly Leu Ala His Phe Val His Asp Glu Asn Ile Ala Leu

65 70 75 80

Leu Val Asp Ala Thr His Pro Phe Ala Ala Arg Ile Ser His Asn Ala

85 90 95

Ala Asp Ala Ala Gln Arg Thr Gly Val Ala Leu Ile Ala Leu Arg Arg

100 105 110

Pro Glu Trp Val Pro Leu Pro Gly Asp Arg Trp Thr Ala Val Asp Ser

115 120 125

Val Val Glu Ala Val Ser Ala Leu Gly Asp Arg Arg Arg Arg Val Phe

130 135 140

Leu Ala Ile Gly Arg Gln Glu Ala Phe His Phe Glu Val Ala Pro Gln

145 150 155 160

His Ser Tyr Val Ile Arg Ser Val Asp Pro Val Thr Pro Pro Leu Asn

165 170 175

Leu Pro Asp Gln Glu Ala Ile Leu Ala Thr Gly Pro Phe Ala Glu Ala

180 185 190

Asp Glu Ala Ala Leu Leu Arg Ser Arg Gln Ile Asp Val Ile Val Ala

195 200 205

Lys Asn Ser Gly Gly Ser Ala Thr Tyr Gly Lys Ile Ala Ala Ala Arg

210 215 220

Arg Leu Gly Ile Glu Val Ile Met Val Glu Arg Arg Lys Pro Ala Asp

225 230 235 240

Val Pro Thr Val Gly Ser Cys Asp Glu Ala Leu Asn Arg Ile Ala His

245 250 255

Trp Leu Ala Pro Ala

260

ATGGCTGACG TGTCGAACAG CGAACCCGCC ATAGTCTCCC CCTGGCTGAC CGTCATCGGT 60

ATCGGTGAGG ATGGTGTAGC GGGTCTCGGC GACGAGGCCA AGCGGCTGAT CGCCGAAGCG 120

CCGGTCGTCT ACGGCGGCCA TCGTCATCTG GAGCTCGCCG CCTCCCTCAT CACCGGCGAA 180

GCGCACAATT GGCTAAGCCC CCTCGAACGC TCGGTCGTCG AGATCGTCGC GCGTCGCGGC 240

AGCCCGGTGG TGGTGCTTGC CTCGGGCGAC CCGTTCTTCT TCGGCGTCGG CGTGACGCTG 300

GCGCGCCGCA TCGCCTCGGC CGAAATACGC ACGCTTCCGG CGCCGTCGTC GATCAGTCTT 360

GCCGCCTCGC GCCTCGGCTG GGCGCTGCAG GATGCGACGC TCGTCTCCGT ACATGGGCGG 420

CCGCTGGATC TGGTGCGACC GCATTTGCAT CCGGGGGCGC GTGTGCTTAC GCTCACGTCG 480

GACGGTGCGG GTCCGCGAGA CCTTGCCGAG CTTCTGGTTT CAAGCGGCTT CGGTCAGTCG 540

CGACTGACCG TGCTCGAAGC GCTGGGCGGC GCCGGCGAAC GGGTGACGAC GCAGATCGCC 600

GCGCGCTTCA TGCTCGGCCT CGTGCATCCT TTGAACGTCT GCGCCATTGA GGTGGCGGCC 660

GACGAGGGCG CGCGCATCCT GCCGCTTGCC GCCGGCCGCG ACGATGCGCT GTTCGAACAT 720

GACGGGCAGA TCACCAAGCG CGAGGTGCGG GCGCTGACGC TGTCGGCACT CGCACCGCGC 780

AAGGGCGAAC TGCTATGGGA CATCGGCGGC GGCTCCGGCT CGATCGGCAT CGAATGGATG 840

CTCGCCGATC CGACCATGCA GGCGATCACC ATCGAGGTTG AGCCGGAGCG GGCAGCGCGC 900

ATCGGCCGCA ACGCGACGAT GTTCGGCGTG CCCGGGCTGA CGGTTGTCGA AGGCGAGGCG 960

CCGGCGGCGC TTGCCGGCCT GCCACAACCG GACGCGATCT TCATCGGCGG CGGCGGCAGC 1020

GAAGACGGCG TCATGGAAGC AGCGATCGAG GCGCTCAAGT CAGGCGGACG GCTGGTTGCC 1080

AACGCGGTGA CGACGGACAT GGAAGCGGTG CTGCTCGATC ATCACGCGCG GCTCGGCGGT 1140

TCGCTGATCC GCATCGATAT CGCGCGTGCA GGACCCATCG GCGGCATGAC CGGCTGGAAG 1200

CCGGCCATGC CGGTCACCCA ATGGTCGTGG ACGAAGGGCT AA 1242

Met Ala Asp Val Ser Asn Ser Glu Pro Ala Ile Val Ser Pro Trp Leu

1 5 10 15

Thr Val Ile Gly Ile Gly Glu Asp Gly Val Ala Gly Leu Gly Asp Glu

20 25 30

Ala Lys Arg Leu Ile Ala Glu Ala Pro Val Val Tyr Gly Gly His Arg

35 40 45

His Leu Glu Leu Ala Ala Ser Leu Ile Thr Gly Glu Ala His Asn Trp

50 55 60

Leu Ser Pro Leu Glu Arg Ser Val Val Glu Ile Val Ala Arg Arg Gly

65 70 75 80

Ser Pro Val Val Val Leu Ala Ser Gly Asp Pro Phe Phe Phe Gly Val

85 90 95

Gly Val Thr Leu Ala Arg Arg Ile Ala Ser Ala Glu Ile Arg Thr Leu

100 105 110

Pro Ala Pro Ser Ser Ile Ser Leu Ala Ala Ser Arg Leu Gly Trp Ala

115 120 125

Leu Gln Asp Ala Thr Leu Val Ser Val His Gly Arg Pro Leu Asp Leu

130 135 140

Val Arg Pro His Leu His Pro Gly Ala Arg Val Leu Thr Leu Thr Ser

145 150 155 160

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

165 170 175

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

180 185 190

Glu Arg Val Thr Thr Gln Ile Ala Ala Arg Phe Met Leu Gly Leu Val

195 200 205

His Pro Leu Asn Val Cys Ala Ile Glu Val Ala Ala Asp Glu Gly Ala

210 215 220

Arg Ile Leu Pro Leu Ala Ala Gly Arg Asp Asp Ala Leu Phe Glu His

225 230 235 240

Asp Gly Gln Ile Thr Lys Arg Glu Val Arg Ala Leu Thr Leu Ser Ala

245 250 255

Leu Ala Pro Arg Lys Gly Glu Leu Leu Trp Asp Ile Gly Gly Gly Ser

260 265 270

Gly Ser Ile Gly Ile Glu Trp Met Leu Ala Asp Pro Thr Met Gln Ala

275 280 285

Ile Thr Ile Glu Val Glu Pro Glu Arg Ala Ala Arg Ile Gly Arg Asn

290 295 300

Ala Thr Met Phe Gly Val Pro Gly Leu Thr Val Val Glu Gly Glu Ala

305 310 315 320

Pro Ala Ala Leu Ala Gly Leu Pro Gln Pro Asp Ala Ile Phe Ile Gly

325 330 335

Gly Gly Gly Ser Glu Asp Gly Val Met Glu Ala Ala Ile Glu Ala Leu

340 345 350

Lys Ser Gly Gly Arg Leu Val Ala Asn Ala Val Thr Thr Asp Met Glu

355 360 365

Ala Val Leu Leu Asp His His Ala Arg Leu Gly Gly Ser Leu Ile Arg

370 375 380

Ile Asp Ile Ala Arg Ala Gly Pro Ile Gly Gly Met Thr Gly Trp Lys

385 390 395 400

Pro Ala Met Pro Val Thr Gln Trp Ser Trp Thr Lys Gly

ATGACGGTAC ATTTCATCGG CGCCGGCCCG GGAGCCGCAG ACCTGATCAC GGTGCGTGGT 60

CGCGACCTGA TCGGGCGCTG CCCGGTCTGC CTTTACGCCG GCTCGATCGT CTCGCCGGAG 120

CTGCTGCGAT ATTGCCCGCC GGGCGCCCGC ATTGTCGATA CGGCGCCGAT GTCCCTCGAC 180

GAGATCGAGG CGGAGTATGT GAAGGCCGAA GCCGAAGGGC TCGACGTGGC GCGGCTTCAT 240

TCGGGCGACC TTTCGGTCTG GAGTGCTGTG GCCGAACAGA TCCGCCGGCT CGAGAAGCAT 300

GGCATCGCCT ATACGATGAC GCCGGGCGTT CCTTCCTTTG CGGCGGCGGC TTCAGCGCTC 360

GGTCGCGAAT TGACCATTCC GGCCGTGGCC CAGAGCCTGG TGCTGACCCG CGTTTCGGGC 420

CGCGCCTCGC CGATGCCGAA CTCAGAAACG CTTTCCGCTT TCGGCGCTAC GGGATCGACG 480

CTGGCAATCC ACCTTGCGAT CCATGCGCTT CAGCAGGTGG TCGAGGAACT GACGCCGCTC 540

TACGGTGCCG ACTGCCCGGT CGCCATCGTC GTCAAGGCCT CCTGGCCGGA CGAACGCGTG 600

GTGCGCGGCA CGCTCGGTGA CATCGCCGCC AAGGTGGCGG AAGAGCCGAT CGAGCGCACG 660

GCGCTGATCT TCGTCGGTCC GGGGCTCGAA GCCTCCGATT TCCGTGAAAG CTCGCTCTAC 720

GATCCCGCCT ATCAGCGGCG CTTCAGAGGG CGCGGCGAAT AG 762

Met Thr Val His Phe Ile Gly Ala Gly Pro Gly Ala Ala Asp Leu Ile

1 5 10 15

Thr Val Arg Gly Arg Asp Leu Ile Gly Arg Cys Pro Val Cys Leu Tyr

20 25 30

Ala Gly Ser Ile Val Ser Pro Glu Leu Leu Arg Tyr Cys Pro Pro Gly

35 40 45

Ala Arg Ile Val Asp Thr Ala Pro Met Ser Leu Asp Glu Ile Glu Ala

50 55 60

Glu Tyr Val Lys Ala Glu Ala Glu Gly Leu Asp Val Ala Arg Leu His

65 70 75 80

Ser Gly Asp Leu Ser Val Trp Ser Ala Val Ala Glu Gln Ile Arg Arg

85 90 95

Leu Glu Lys His Gly Ile Ala Tyr Thr Met Thr Pro Gly Val Pro Ser

100 105 110

Phe Ala Ala Ala Ala Ser Ala Leu Gly Arg Glu Leu Thr Ile Pro Ala

115 120 125

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

130 135 140

Met Pro Asn Ser Glu Thr Leu Ser Ala Phe Gly Ala Thr Gly Ser Thr

145 150 155 160

Leu Ala Ile His Leu Ala Ile His Ala Leu Gln Gln Val Val Glu Glu

165 170 175

Leu Thr Pro Leu Tyr Gly Ala Asp Cys Pro Val Ala Ile Val Val Lys

180 185 190

Ala Ser Trp Pro Asp Glu Arg Val Val Arg Gly Thr Leu Gly Asp Ile

195 200 205

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

210 215 220

Val Gly Pro Gly Leu Glu Ala Ser Asp Phe Arg Glu Ser Ser Leu Tyr

225 230 235 240

Asp Pro Ala Tyr Gln Arg Arg Phe Arg Gly Arg Gly Glu

GTCGACGAGT ATGGTCAGGT TCAGGGTCTG GTGACGCTGG AGGACATTCT GGAGGAGATC 60

GTCGGCGATA TCGCCGATGA GCACGACCTC GACATTCAGG GCGTGCGCCA GGAAGCCGAT 120

GGCTCGATCG TCGTCGATGG CTCGGTGCCG ATCCGCGATC TCAACCGCGC GCTCGACTGG 180

TCGCTGCCGG ACGAGGAGGC GACGACGGTG GCCGGTCTGG TCATCCACGA GTCCAAGAGC 240

ATTCCGGAGG AGCGCCAGGC CTTCACCTTC CACGGCAAAC GCTTCATCGT GATGAAGCGG 300

GTGAAGAACC GCATTACCAA GCTGCGCATC CGTCCGGCGG AAGAGGGTGC TCCGCCGGCG 360

TGATGGCCGC GATTGCCTCT ACCAGCGGGT CGGCTCGCCG GGGGCTGCCG GCTCGACGGC 420

GAGCGCATGC AGGCCGGCGT CGAGTTCTGG CTTCAGGAGA TCATTGATGG CGCGGTGGCG 480

GGCGACACGG CTCATGCCGG CAAAGGCGCT AGAAACGATA CGCACCCGCA TGTGGGACTC 540

GCCGGTACCA TCGAAGCCCG GCTGATGGCC GGTATGCTGA TGGCTCTCGT TGATGACCTC 600

GAGCCGTTCA GGGTGGAAGG CCTCGATCAG CTTCTTTTCG ATGGTCTCGG TGAGCGACAT 660

TCTTCCGTCC CATTTTGCTG TTTGCTTGGC GCCCCCTCGC AGTTAAGAAC CCGGTAATCG 720

CTGGCACGGC GGCGCAAAAT GCCCGCACAA AGCCAGCAAC ATTCCGCTTT GTCAATTCTT 780

GTTGTGACTC CCGCCAAACC CCATAATGAG CGCCATGAGA CTCGATTCAA AATACTTCGA 840

TCGCATTCGA ACCCGGCGCA AGGTCGAGCC GCAGCAGAGC CGGCGGCTCC CGTCTGTCAG 900

TGGGACGGCT GCGATCAGAA GGGTGTGCAC CGGGCGCCCG TCGGTCGCAA CGCCGAGGGG 960

CAGTACTTCA TGTTCTGCTT CGAGCACGTG AAGGAATACA ACAAGGGCTA CAACTTCTTC 1020

TCCGGCCTCT CCGACAGCGA GGTCGCCCGC TACCAGAAGG AAGCGATCAC CGGTCATCGG 1080

CCCACCTGGA CCGTCGGCGT CAACAAGAAC GCCAAGAACG GCCCGACCCA GTCGCAGACG 1140

CGGTCTGGCT CTGCCGGCGC CCAGGCCCGC ATGCGCGATC CCTTCGGCTT TGTCAGCGAG 1200

GCGCGGGCGC GATCCGGTCG TCCCGAGCCA CGCCAGCGCA AGCTGAAGAC GCTCGAGGCG 1260

AAGGCCTTCG AAACGCTTGG TCTCGGAGCC TCGGCGACCA CTGCCGACAT CAAGGCGGCC 1320

TACAAGGACC TCGTCAAGAA GCATCACCCC GATGCCAATG GCGGAGATAG AGGATCGGAA 1380

GAGCGTTTTC GCGCGGTTAT TCAGGCCTAC CAATTGTTAA AACAGGCTGG TTTCTGCTAA 1440

CAACCCGGAT TAATACAGAA GCACTTTTGC AGGCGAATGC GCGGGTGCCG TCCGGTGGCC 1500

GCTCTGGAGA CATGATGAGC AAGATTGACC TCGACATTTC CAACCTCCCC GACACCACGA 1560

TTTCCGTCCG GGAGGTTTTC GGTATTGATA CGGATTTGCG CGTTCCTGCC TATTCGAAGG 1620

GCGACGCCTA TGTCCCGGAT CTGGATCCGG ACTACCTCTT CGACCGCGAA ACGACGCTCG 1680

CCATTCTCGC AGGCTTCGCC CACAACCGAC GCGTGATGGT GTCGGGCTAT CACGGCACCG 1740

GCAAGTCCAC CCATATCGAG CAGGTCGCCG CGCGCCTCAA CTGGCCGTGC GTGCGCGTCA 1800

ACCTCGATAG CCATGTCAGC CGTATCGACC TCGTCGGCAA GGACGCGATC GTCGTCAAGG 1860

ACGGCCTGCA GGTCACCGAA TTCAAGGACG GCATCCTGCC CTGGGCCTAC CAGCACAATG 1920

TCGCGCTCGT CTTCGACGAA TACGATGCCG GCCGCCCGGA CGTCATGTTC GTCATCCAGC 1980

GCGTGCTGGA ATCCTCCGGC CGCCTGACGC TGCTCGACCA GAGCCGTGTC ATCCGTCCGC 2040

ACCCGGCCTT CCGCCTGTTT GCGACCGCCA ACACCGTCGG CCTCGGCGAC ACGACCGGCC 2100

TCTATCACGG CACGCAGCAG ATCAACCAGG CGCAGATGGA CCGCTGGTCG ATCGTCACCA 2160

CGCTGAACTA CCTGCCGCAC GACAAGGAAG TCGACATCGT CGCCGCCAAG GTCAAGGGCT 2220

TCACCGCCGA CAAGGGCCGC GAGACCGTCT CCAAGATGGT ACGTGTCGCC GACCTCACGC 2280

GCGCAGCCTT CATCAATGGC GATCTCTCGA CTGTCATGAG CCCGCGTACG GTCATCACCT 2340

GGGCCGAGAA CGCCCACATC TTCGGCGACA TCGCTTTCGC CTTCCGCGTG ACCTTCCTCA 2400

ACAAGTGCGA CGAGCTGGAG CGGGCGCTGG TCGCCGAGCA CTACCAGCGC GCCTTCGGCA 2460

TCGAGCTGAA GGAATGCGCT GCCAACATCG TGCTCGAAGC CACCGCCTGA TCCCACGGCC 2520

TGCCGTCCCC TTTGGGAGGG CGGGTCATGA CGCTGTGGCA AACCGGATGA CGCCCCACTG 2580

GGGCGCCGTC GCCTCTGGCT GAAGAAGGAA CTGTCGTGAG CTCGAATTCG AAGGCAAAGC 2640

CAACCACGCG CGAGAATGCT GCGGAACCGT TCAAGCGGGC GCTTTCCGGC TGCATCCGAT 2700

CGATCGCGGG CGATGCCGAG GTGGAAGTCG CCTTCGCCAA CGAGCGGCCG GGCATGACCG 2760

GCGAACGCAT CCGTCTGCCG GAACTTTCCA AGCGCCCGAC CCTGCAGGAA CTTGCCGTGA 2820

CCCGCGGGCT CGGTGACAGC ATGGCGCTGC GCAAGGCCTG TACGCATGCG CGGATCCAGC 2880

GCACCATGTC GCCGCAAGGG GCGGACGCCC GCGCGATCTT CGATGCGGTG GAGCAGGCTC 2940

GTGTCGAGGC GATCGGGTCG TTGCGCATGG CGGGTGTCGC CAAGAACCTC AACGTCATGC 3000

TCGAAGAGAA ATACGCCAAG GCGAATTTCG CAACGATCGA GCGCCAGGCG GACGCGCCGC 3060

TCGGCGAGGC CGTAGCGCTG CTGGTGCGCG AGAAGCTGAC GGGCCAGAAG CCGCCGGCGT 3120

CTGCCGGCAA GGTGCTCGAC CTCTGGCGCG AGTTCATCGA GGGCAAGGCT GCCGGCGACA 3180

TTGAGCACCT GTCGTCGACG ATCAACAACC AGCAGGCCTT TGCCCGGGTC GTTCGCGACA 3240

TGCTGACCTC GATGGAAGTC GCCGAGAAAT ACGGTGACGA CGACAACGAG CCGGACGAGC 3300

AGGAAAGCGA GACCGACGAA GACCAGCCGC GCAGCCAGGA GCAGGACGAG AACGCCAGCG 3360

ACGAGGAAGC CGGCGACGAT GCCGCACCCG CCGACGAGAA CCAGGCTGCC GAAGAGCAGA 3420

TGGAAGAAGG CGAGATGGAC GGCGCGGAGA TCTCCGACGA CGATCTCCAG GACGAAGGCG 3480

ACGAGGACAG CGAAACGCCC GGCGAGGTCA AGCGTCCGAA CCAGCCCTTC GCCGACTTCA 3540

ACGAGAAGGT CGACTACGCC GTCTTCACCC GCGAGTTCGA CGAGACGATT GCCTCGGAAG 3600

AGCTTTGCGA CGAGGCCGAG CTCGACCGGC TGCGCGCCTT CCTCGACAAG CAGCTTGCCC 3660

ATCTTCAAGG CGCGGTCGGC CGCCTTGCCA ACCGGCTGCA GCGCCGCCTG ATGGCGCAGC 3720

AGAACCGCTC CTGGGAGTTC GATCTCGAAG AGGGGTATCT CGATTCGGCG CGGCTTCAGC 3780

GCATCATCAT CGATCCGATG CAGCCGCTTT CCTTCAAGCG CGAAAAGGAC ACCAACTTCC 3840

GCGATACCGT CGTGACGCTG CTGATCGACA ATTCCGGCTC GATGCGCGGC CGTCCGATCA 3900

CGGTTGCCGC CACCTGCGCC GATATCCTGG CGCGCACGCT CGAGCGCTGC GGCGTCAAGG 3960

TCGAGATCCT CGGTTTTACC ACCAAGGCGT GGAAGGGTGG GCAGTCACGC GAGAAGTGGC 4020

TGGCCGGCGG CAAGCCACAG GCCCCGGGTC GCCTCAACGA CCTGCGACAC ATCGTCTACA 4080

AGTCTGCCGA CGCTCCGTGG CGCCGGGCAC GACGCAATCT CGGCCTGATG ATGCGGGAAG 4140

GCCTGCTCAA GGAAAACATC GACGGCGAGG CGTTGATTTG GGCGCATGAG CGGCTGATGG 4200

CGCGGCGCGA ACAGCGGCGC ATCCTGATGA TGATTTCGGA CGGCGCGCCG GTCGACGACT 4260

CGACGCTGTC GGTCAATCCA GGAAACTATC TGGAGCGTCA CCTGCGCGCG GTCATCGAGC 4320

AGATCGAAAC GCGCTCGCCG GTGGAACTGC TGGCGATCGG TATCGGCCAC GACGTGACGC 4380

GCTACTATCG CCGTGCCGTC ACCATCGTCG ATGCCGATGA GCTTGCCGGC GCGATGACCG 4440

AACAGCTGGC CGCACTCTTC GAGGACGAAA GCCAGCGCCG CGGTTCTTCG CGTCTTCGCC 4500

GCGCCGGGTG ATGCTTCCCC CTTGGGGGCG GTGGAACATC GCCTCCGAGC TGCCAATCGG 4560

CACCTGCACG CATCGCTGGC GGCCGAAGTC AATTTACGGA CATAGTTTTA CAGTCTACCA 4620

AGCTACCATG CGTGGCGGGC TCACTTTGAG CGCACGCCGC GTCATTCCCG ATGCCCCCTG 4680

AAGGTACTTC TCTTGATGCT TGGCCGCGGT CTCCTAGCCC TTTTCCTCCT GGCTTCGGCC 4740

TGCCCGGC 4748

GAGCTCATAG AGCAGTTCCT CGATCGACTT CAGCAGTCGC ATGAAATCCA TGCCGTGCTC 60

CCCTTGCTTC TATGCGTGGC ACGACCGCGC GCCGGGGCCG ATGCCGGTCA GTCGCGCAGA 120

CGCAGCTCGT CGGTACGCAT CTGCAGCATC TCCAGCGTCG ACAGGAAGCT CATGCCGAGC 180

AGGCTCTGAT CGAGCTTGCC CTTGGCTGCG ACCGTTGCGC CGATGTTGCG GCGGGTGATC 240

GGGCCGATCG AGATCTCCTG AAGCATCACG GGGGCTGCCT GGGCCCGGCC ATTGGCTGTC 300

ATGACCGTGA CGATAAAGTT GAGGTTGGCC GGGTCGAGGC CGATCTTTTC CGCATCTTCA 360

TAGGTGAGCG CGATGTTGCT GGCGCCGGTA TCGACCAGCA TGCTGATGTC CTTGCCGTCG 420

ACCGTCGCAG TGGTCTCGAA ATGACCGTTC AGCATCTTCT GCAGCACCAC TTCCTGCTGT 480

CCCTCGCTGT CAGTGATGAT GGTGGCGCGG CCGGGGATGA GGCCGGCGAG CAGGCGGTTA 540

CCGAAGCCCT CCAACTCGAA GCGGTAGACA TAGGCCGAGA CCAGCGCCAG AACGACGAAG 600

AGCCAGATGG CGATCTGACG CAGGCCTTCG CCGAAGCGGT GGCGGCTCTG CAGGATGCCG 660

GCGCCGATCA GCGTGGCGAT GGCGCCGAGC GAGACCAGTT GCCCGAACTG GTCATTGGCA 720

AGCCCCATGG TGCGGCCGGT GTCGTGGTTG ATGATCAGCA GGATGAGGCC GATGGCCAGG 780

ATCGAGAGCA GGATGGCAAG ACGGGTCATG CTTCGCCGCG TTCCCTCGCC ATGCGCGTGC 840

GTCGGGTTTC GCGCCGCGGC TTGCGTTCGA CGGTCTCAAG CCGTGCAGGC AACGCGCTCA 900

TGATCGCGCG GCGTTCGGCA TCGGTATAGA GCGTCCAGCG TCCGACTTCG TCGCGGGTAC 960

GGCCGCAGCC GAAACAGTAG CCGGTCTTGT CATCGATCGA ACAGACGAGA ATGCAGGGAG 1020

ATTCCATGGG CGTGCTCAGT TTTCCCTTGA TATATCGATG TTTCAAACCG TCAGCGCAAG 1080

GGCACCGAGC ACGGCGATTT CGGTCAGTTG CTGCGTCGCC CCGATCGTGT CGCCCGTTTG 1140

TCCGCCGATC TTGCGCATCG CCAGCCGAGC GAAGCCCTTG ACCGTGGCAA GGAATGCGAC 1200

GAGCGCCGCG ATGACGCCGA GCGCCGGGAC CTGCGCGAGA TAGAAGAGCA GCATTGCGAC 1260

AAGAAGTCCG AAGGCAAGCG CGAAGCGCGT GGCCGCCGGT TCCGGCTCGC CAGCCGAGGC 1320

CGCGACGCCG CTGCTGCGCG CCGGCGGAAG CGACGACCAG TGCCAGACCA TGGCGGCGCG 1380

GCTGAGGCAC GCTGCGCCAA GGATCGCCAT GGCGGCGCCC AGCGGCGAAA AGAGCGGCAG 1440

GATCGAGGCG AACGCCGAGA CGCGCAGGCC GAAGGAGAGG ATGAGGGCGA CGGCCGCATA 1500

GGTGCCGATG CGGCTGTCCT TCATGATCGC AAGCGCCGCT TCGCGGTCGC GACCGCCGCC 1560

AAAGCCATCG GCCGTGTCGC CAAGCCCGTC TTCGTGCAGT GCGCCGGTGA CAAGCGCCTG 1620

GATGGCGACG ACGACAAAGG CGGCAAAGAG CGAGCTCACC TGCAGCGCCA TGAGGGCCAT 1680

GGCGACGGCC GCCGATGGCA GTGCGATCGC CAGGCCGGCG AACGGGAAGG CGCGCACGGC 1740

ACGGCTCAAG CGCCCGTCAT AACCTTCGAA ATGACGCGCA GGCATCGGGA TGCGGCTGAG 1800

AAAGCCGATC GACCGCGCCA CATCGTCACA GAAATCGCCA ACGAAGCCCA TGGCTCCTCC 1860

AAGGTTGCGG CCATTGACCC GGCCGCTGCC AAACTCGCCG ACTGCGGCGA GTCTCGCAAG 1920

CCGGGCGGGC GCACCCGCGA GGGCCGCGCA CACTTTTCCC AGACCTTTCA TAGGCCGTCT 1980

GCGACCGCTC GCGGATCGAG ACGGCGACGC CGATTGGCGC AAATGTCGTT GCCCGAATTT 2040

TCGGCGCCCT CTATGAGGGG CGTAGATAGA GCTTCACGAT GATGCAAGGA TTCCTCCCAT 2100

GAGTGCCAGC GGCCTGCCGT TTGATGATTT TCGCGAATTG TTGCGCAACC TGCCGGGCCC 2160

GGATGCGGCA GCCCTCGTTG CCGCGCGGGA GCGGGACGCC CAGCTGACGA AGCCGCCGGG 2220

CGCGCTCGGC CGCCTCGAGG AAATCGCCTT CTGGCTCGCC GCCTGGACGG GCAAGGCGCC 2280

GGTGGTCAAC CGGCCGCTGG TGGCGATCTT TGCCGGCAAC CACGGCGTCA CCCGCCAGGG 2340

GGTGACCCCG TTCCCGTCAT CCGTCACCGC ACAGATGGTC GAGAATTTTG CCGCCGGTGG 2400

CGCTGCGATC AACCAGATCT GCGTCAGCCA CGACCTCGGG CTGAAGGTCT TCGACCTCGC 2460

ACTCGAATAC CCGACCGGTG ATATCACCGA GGAAGCCGCG CTGTCCGAGC GCGATTGCGC 2520

CGCGACCATG GCCTTTGGCA TGGAGGCGAT TGCCGGCGGC ACGGATCTTC TGTGCATCGG 2580

CGAAATGGGC ATCGGCAACA CCACGATCGC GGCCGCGATC AATCTCGGCC TTTATGGTGG 2640

CACGGCCGAA GAATGGGTCG GTCCGGGTAC CGGCTCCGAG GGCGAGGTGC TGAAGCGCAA 2700

GATCGCCGCG GTCGAAAAGG CCGTGGCGCT GCATCGCGAT CACCTGTCCG ATCCGCTCGA 2760

ACTGATGCGT CGCCTCGGCG GTCGTGAGAT CGCGGCCATG GCTGGCGCCA TCCTGGCCGC 2820

CCGCGTCCAG AAGGTACCTG TCATCATCGA CGGCTACGTG GCGACCGCTG CGGCTTCGAT 2880

CCTGAAGGCG GCCAACCCGT CGGCCCTCGA CCATTGCCTG ATCGGCCATG TTTCGGGCGA 2940

ACCGGGGCAT CTGCGCGCGA TCGAGAAGCT CGGCAAGACG CCGCTGCTGG CACTCGGCAT 3000

GCGGCTTGGC GAAGGCACGG GCGCGGCCCT TGCCGCCGGT ATCGTCAAGG CGGCGGCCGC 3060

TTGCCACAGC GGCATGGCGA CCTTTGCCCA GGCCGGCGTC AGCAACAAGG AATAGTGAAG 3120

TTCCGGCCGG GCTTTGCAGG AAGGCCGGCC GGTTTCTGTC CAAGGCCTGT CACGGGCGCG 3180

AAGCTGTCGC GTGCCGGGCC TTGATGGATG CGTCCTTCTC GCCTATCCAA AGCGCAAATG 3240

CGCGCCCTAG CTATAGTCTT GGGTGCCTGC AACCGAGACC GCCTTGCATT CGCCTCAATC 3300

ACGATGTCGA AGCAAGCACA GTTTCAAGCC CTGTCGAGAC GAAATGGACG CCAAGAACAC 3360

CACGCACCGC ATTGGACAGA CGGGTCCTGT CGAGAAGCAG ACCGGCATTC GGCATCTCTT 3420

TGCCGCTGCG AGCTATTCGC TCGGCGGCGC CAAGCGGCTG ATCGGCGAGG CTGCCTTTCG 3480

CCACGAGCTG ATCGCCTTTG CCGCCGCGAT GATCGCTTTC ATCATCGTCG GCGCAACCTT 3540

CTTCCAATAT GTGGCGATGG CGATCCTGTT CCTGCTGATG ATGGCCTTCG AGGCGATCAA 3600

CACGGCAATC GAGGAAATTG TCGATCGCGT TTCTCCCGAA ATCTCGGAAA TGGGTAAGAA 3660

CGCCAAGGAT CTCGGCTCCT TCGCCTGCCT CTGCCTGATT GTCGCCAACG GTGTCTATGC 3720

CGCCTATGTC GTGATCTTCG ACGGCTTCAT GAACTGACCG GCTAGCGGGC CGGCGCCTTC 3780

ACCCGATAAA GCACATGCGG ACGCAGCGGG TTGCCCCCGG GTACCGTGAC GTCGTCGAAA 3840

TCATCAGCCG GATCC 3855

ATGATGAGCA AGATTGACCT CGACATTTCC AACCTCCCCG ACACCACGAT TTCCGTCCGG 60

GAGGTTTTCG GTATTGATAC GGATTTGCGC GTTCCTGCCT ATTCGAAGGG CGACGCCTAT 120

GTCCCGGATC TGGATCCGGA CTACCTCTTC GACCGCGAAA CGACGCTCGC CATTCTCGCA 180

GGCTTCGCCC ACAACCGACG CGTGATGGTG TCGGGCTATC ACGGCACCGG CAAGTCCACC 240

CATATCGAGC AGGTCGCCGC GCGCCTCAAC TGGCCGTGCG TGCGCGTCAA CCTCGATAGC 300

CATGTCAGCC GTATCGACCT CGTCGGCAAG GACGCGATCG TCGTCAAGGA CGGCCTGCAG 360

GTCACCGAAT TCAAGGACGG CATCCTGCCC TGGGCCTACC AGCACAATGT CGCGCTCGTC 420

TTCGACGAAT ACGATGCCGG CCGCCCGGAC GTCATGTTCG TCATCCAGCG CGTGCTGGAA 480

TCCTCCGGCC GCCTGACGCT GCTCGACCAG AGCCGTGTCA TCCGTCCGCA CCCGGCCTTC 540

CGCCTGTTTG CGACCGCCAA CACCGTCGGC CTCGGCGACA CGACCGGCCT CTATCACGGC 600

ACGCAGCAGA TCAACCAGGC GCAGATGGAC CGCTGGTCGA TCGTCACCAC GCTGAACTAC 660

CTGCCGCACG ACAAGGAAGT CGACATCGTC GCCGCCAAGG TCAAGGGCTT CACCGCCGAC 720

AAGGGCCGCG AGACCGTCTC CAAGATGGTA CGTGTCGCCG ACCTCACGCG CGCAGCCTTC 780

ATCAATGGCG ATCTCTCGAC TGTCATGAGC CCGCGTACGG TCATCACCTG GGCCGAGAAC 840

GCCCACATCT TCGGCGACAT CGCTTTCGCC TTCCGCGTGA CCTTCCTCAA CAAGTGCGAC 900

GAGCTGGAGC GGGCGCTGGT CGCCGAGCAC TACCAGCGCG CCTTCGGCAT CGAGCTGAAG 960

GAATGCGCTG CCAACATCGT GCTCGAAGCC ACCGCCTGA 999

Met Met Ser Lys Ile Asp Leu Asp Ile Ser Asn Leu Pro Asp Thr Thr

1 5 10 15

Ile Ser Val Arg Glu Val Phe Gly Ile Asp Thr Asp Leu Arg Val Pro

20 25 30

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

35 40 45

Leu Phe Asp Arg Glu Thr Thr Leu Ala Ile Leu Ala Gly Phe Ala His

50 55 60

Asn Arg Arg Val Met Val Ser Gly Tyr His Gly Thr Gly Lys Ser Thr

65 70 75 80

His Ile Glu Gln Val Ala Ala Arg Leu Asn Trp Pro Cys Val Arg Val

85 90 95

Asn Leu Asp Ser His Val Ser Arg Ile Asp Leu Val Gly Lys Asp Ala

100 105 110

Ile Val Val Lys Asp Gly Leu Gln Val Thr Glu Phe Lys Asp Gly Ile

115 120 125

Leu Pro Trp Ala Tyr Gln His Asn Val Ala Leu Val Phe Asp Glu Tyr

130 135 140

Asp Ala Gly Arg Pro Asp Val Met Phe Val Ile Gln Arg Val Leu Glu

145 150 155 160

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

165 170 175

His Pro Ala Phe Arg Leu Phe Ala Thr Ala Asn Thr Val Gly Leu Gly

180 185 190

Asp Thr Thr Gly Leu Tyr His Gly Thr Gln Gln Ile Asn Gln Ala Gln

195 200 205

Met Asp Arg Trp Ser Ile Val Thr Thr Leu Asn Tyr Leu Pro His Asp

210 215 220

Lys Glu Val Asp Ile Val Ala Ala Lys Val Lys Gly Phe Thr Ala Asp

225 230 235 240

Lys Gly Arg Glu Thr Val Ser Lys Met Val Arg Val Ala Asp Leu Thr

245 250 255

Arg Ala Ala Phe Ile Asn Gly Asp Leu Ser Thr Val Met Ser Pro Arg

260 265 270

Thr Val Ile Thr Trp Ala Glu Asn Ala His Ile Phe Gly Asp Ile Ala

275 280 285

Phe Ala Phe Arg Val Thr Phe Leu Asn Lys Cys Asp Glu Leu Glu Arg

290 295 300

Ala Leu Val Ala Glu His Tyr Gln Arg Ala Phe Gly Ile Glu Leu Lys

305 310 315 320

Glu Cys Ala Ala Asn Ile Val Leu Glu Ala Thr Ala

GTGAGCTCGA ATTCGAAGGC AAAGCCAACC ACGCGCGAGA ATGCTGCGGA ACCGTTCAAG 60

CGGGCGCTTT CCGGCTGCAT CCGATCGATC GCGGGCGATG CCGAGGTGGA AGTCGCCTTC 120

GCCAACGAGC GGCCGGGCAT GACCGGCGAA CGCATCCGTC TGCCGGAACT TTCCAAGCGC 180

CCGACCCTGC AGGAACTTGC CGTGACCCGC GGGCTCGGTG ACAGCATGGC GCTGCGCAAG 240

GCCTGTACGC ATGCGCGGAT CCAGCGCACC ATGTCGCCGC AAGGGGCGGA CGCCCGCGCG 300

ATCTTCGATG CGGTGGAGCA GGCTCGTGTC GAGGCGATCG GGTCGTTGCG CATGGCGGGT 360

GTCGCCAAGA ACCTCAACGT CATGCTCGAA GAGAAATACG CCAAGGCGAA TTTCGCAACG 420

ATCGAGCGCC AGGCGGACGC GCCGCTCGGC GAGGCCGTAG CGCTGCTGGT GCGCGAGAAG 480

CTGACGGGCC AGAAGCCGCC GGCGTCTGCC GGCAAGGTGC TCGACCTCTG GCGCGAGTTC 540

ATCGAGGGCA AGGCTGCCGG CGACATTGAG CACCTGTCGT CGACGATCAA CAACCAGCAG 600

GCCTTTGCCC GGGTCGTTCG CGACATGCTG ACCTCGATGG AAGTCGCCGA GAAATACGGT 660

GACGACGACA ACGAGCCGGA CGAGCAGGAA AGCGAGACCG ACGAAGACCA GCCGCGCAGC 720

CAGGAGCAGG ACGAGAACGC CAGCGACGAG GAAGCCGGCG ACGATGCCGC ACCCGCCGAC 780

GAGAACCAGG CTGCCGAAGA GCAGATGGAA GAAGGCGAGA TGGACGGCGC GGAGATCTCC 840

GACGACGATC TCCAGGACGA AGGCGACGAG GACAGCGAAA CGCCCGGCGA GGTCAAGCGT 900

CCGAACCAGC CCTTCGCCGA CTTCAACGAG AAGGTCGACT ACGCCGTCTT CACCCGCGAG 960

TTCGACGAGA CGATTGCCTC GGAAGAGCTT TGCGACGAGG CCGAGCTCGA CCGGCTGCGC 1020

GCCTTCCTCG ACAAGCAGCT TGCCCATCTT CAAGGCGCGG TCGGCCGCCT TGCCAACCGG 1080

CTGCAGCGCC GCCTGATGGC GCAGCAGAAC CGCTCCTGGG AGTTCGATCT CGAAGAGGGG 1140

TATCTCGATT CGGCGCGGCT TCAGCGCATC ATCATCGATC CGATGCAGCC GCTTTCCTTC 1200

AAGCGCGAAA AGGACACCAA CTTCCGCGAT ACCGTCGTGA CGCTGCTGAT CGACAATTCC 1260

GGCTCGATGC GCGGCCGTCC GATCACGGTT GCCGCCACCT GCGCCGATAT CCTGGCGCGC 1320

ACGCTCGAGC GCTGCGGCGT CAAGGTCGAG ATCCTCGGTT TTACCACCAA GGCGTGGAAG 1380

GGTGGGCAGT CACGCGAGAA GTGGCTGGCC GGCGGCAAGC CACAGGCCCC GGGTCGCCTC 1440

AACGACCTGC GACACATCGT CTACAAGTCT GCCGACGCTC CGTGGCGCCG GGCACGACGC 1500

AATCTCGGCC TGATGATGCG GGAAGGCCTG CTCAAGGAAA ACATCGACGG CGAGGCGTTG 1560

ATTTGGGCGC ATGAGCGGCT GATGGCGCGG CGCGAACAGC GGCGCATCCT GATGATGATT 1620

TCGGACGGCG CGCCGGTCGA CGACTCGACG CTGTCGGTCA ATCCAGGAAA CTATCTGGAG 1680

CGTCACCTGC GCGCGGTCAT CGAGCAGATC GAAACGCGCT CGCCGGTGGA ACTGCTGGCG 1740

ATCGGTATCG GCCACGACGT GACGCGCTAC TATCGCCGTG CCGTCACCAT CGTCGATGCC 1800

GATGAGCTTG CCGGCGCGAT GACCGAACAG CTGGCCGCAC TCTTCGAGGA CGAAAGCCAG 1860

CGCCGCGGTT CTTCGCGTCT TCGCCGCGCC GGGTGA 1896

Val Ser Ser Asn Ser Lys Ala Lys Pro Thr Thr Arg Glu Asn Ala Ala

1 5 10 15

Glu Pro Phe Lys Arg Ala Leu Ser Gly Cys Ile Arg Ser Ile Ala Gly

20 25 30

Asp Ala Glu Val Glu Val Ala Phe Ala Asn Glu Arg Pro Gly Met Thr

35 40 45

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

50 55 60

Glu Leu Ala Val Thr Arg Gly Leu Gly Asp Ser Met Ala Leu Arg Lys

65 70 75 80

Ala Cys Thr His Ala Arg Ile Gln Arg Thr Met Ser Pro Gln Gly Ala

85 90 95

Asp Ala Arg Ala Ile Phe Asp Ala Val Glu Gln Ala Arg Val Glu Ala

100 105 110

Ile Gly Ser Leu Arg Met Ala Gly Val Ala Lys Asn Leu Asn Val Met

115 120 125

Leu Glu Glu Lys Tyr Ala Lys Ala Asn Phe Ala Thr Ile Glu Arg Gln

130 135 140

Ala Asp Ala Pro Leu Gly Glu Ala Val Ala Leu Leu Val Arg Glu Lys

145 150 155 160

Leu Thr Gly Gln Lys Pro Pro Ala Ser Ala Gly Lys Val Leu Asp Leu

165 170 175

Trp Arg Glu Phe Ile Glu Gly Lys Ala Ala Gly Asp Ile Glu His Leu

180 185 190

Ser Ser Thr Ile Asn Asn Gln Gln Ala Phe Ala Arg Val Val Arg Asp

195 200 205

Met Leu Thr Ser Met Glu Val Ala Glu Lys Tyr Gly Asp Asp Asp Asn

210 215 220

Glu Pro Asp Glu Gln Glu Ser Glu Thr Asp Glu Asp Gln Pro Arg Ser

225 230 235 240

Gln Glu Gln Asp Glu Asn Ala Ser Asp Glu Glu Ala Gly Asp Asp Ala

245 250 255

Ala Pro Ala Asp Glu Asn Gln Ala Ala Glu Glu Gln Met Glu Glu Gly

260 265 270

Glu Met Asp Gly Ala Glu Ile Ser Asp Asp Asp Leu Gln Asp Glu Gly

275 280 285

Asp Glu Asp Ser Glu Thr Pro Gly Glu Val Lys Arg Pro Asn Gln Pro

290 295 300

Phe Ala Asp Phe Asn Glu Lys Val Asp Tyr Ala Val Phe Thr Arg Glu

305 310 315 320

Phe Asp Glu Thr Ile Ala Ser Glu Glu Leu Cys Asp Glu Ala Glu Leu

325 330 335

Asp Arg Leu Arg Ala Phe Leu Asp Lys Gln Leu Ala His Leu Gln Gly

340 345 350

Ala Val Gly Arg Leu Ala Asn Arg Leu Gln Arg Arg Leu Met Ala Gln

355 360 365

Gln Asn Arg Ser Trp Glu Phe Asp Leu Glu Glu Gly Tyr Leu Asp Ser

370 375 380

Ala Arg Leu Gln Arg Ile Ile Ile Asp Pro Met Gln Pro Leu Ser Phe

385 390 395 400

Lys Arg Glu Lys Asp Thr Asn Phe Arg Asp Thr Val Val Thr Leu Leu

405 410 415

Ile Asp Asn Ser Gly Ser Met Arg Gly Arg Pro Ile Thr Val Ala Ala

420 425 430

Thr Cys Ala Asp Ile Leu Ala Arg Thr Leu Glu Arg Cys Gly Val Lys

435 440 445

Val Glu Ile Leu Gly Phe Thr Thr Lys Ala Trp Lys Gly Gly Gln Ser

450 455 460

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

465 470 475 480

Asn Asp Leu Arg His Ile Val Tyr Lys Ser Ala Asp Ala Pro Trp Arg

485 490 495

Arg Ala Arg Arg Asn Leu Gly Leu Met Met Arg Glu Gly Leu Leu Lys

500 505 510

Glu Asn Ile Asp Gly Glu Ala Leu Ile Trp Ala His Glu Arg Leu Met

515 520 525

Ala Arg Arg Glu Gln Arg Arg Ile Leu Met Met Ile Ser Asp Gly Ala

530 535 540

Pro Val Asp Asp Ser Thr Leu Ser Val Asn Pro Gly Asn Tyr Leu Glu

545 550 555 560

Arg His Leu Arg Ala Val Ile Glu Gln Ile Glu Thr Arg Ser Pro Val

565 570 575

Glu Leu Leu Ala Ile Gly Ile Gly His Asp Val Thr Arg Tyr Tyr Arg

580 585 590

Arg Ala Val Thr Ile Val Asp Ala Asp Glu Leu Ala Gly Ala Met Thr

595 600 605

Glu Gln Leu Ala Ala Leu Phe Glu Asp Glu Ser Gln Arg Arg Gly Ser

610 615 620

Ser Arg Leu Arg Arg Ala Gly

625 630

ATGTCGCTCA CCGAGACCAT CGAAAAGAAG CTGATCGAGG CCTTCCACCC TGAACGGCTC 60

GAGGTCATCA ACGAGAGCCA TCAGCATACC GGCCATCAGC CGGGCTTCGA TGGTACCGGC 120

GAGTCCCACA TGCGGGTGCG TATCGTTTCT AGCGCCTTTG CCGGCATGAG CCGTGTCGCC 180

CGCCACCGCG CCATCAATGA TCTCCTGAAG CCAGAACTCG ACGCCGGCCT GCATGCGCTC 240

GCCGTCGAGC CGGCAGCCCC CGGCGAGCCG ACCCGCTGGT AG 282

Met Ser Leu Thr Glu Thr Ile Glu Lys Lys Leu Ile Glu Ala Phe His

1 5 10 15

Pro Glu Arg Leu Glu Val Ile Asn Glu Ser His Gln His Thr Gly His

20 25 30

Gln Pro Gly Phe Asp Gly Thr Gly Glu Ser His Met Arg Val Arg Ile

35 40 45

Val Ser Ser Ala Phe Ala Gly Met Ser Arg Val Ala Arg His Arg Ala

50 55 60

Ile Asn Asp Leu Leu Lys Pro Glu Leu Asp Ala Gly Leu His Ala Leu

65 70 75 80

Ala Val Glu Pro Ala Ala Pro Gly Glu Pro Thr Arg Trp

ATGAGTGCCA GCGGCCTGCC GTTTGATGAT TTTCGCGAAT TGTTGCGCAA CCTGCCGGGC 60

CCGGATGCGG CAGCCCTCGT TGCCGCGCGG GAGCGGGACG CCCAGCTGAC GAAGCCGCCG 120

GGCGCGCTCG GCCGCCTCGA GGAAATCGCC TTCTGGCTCG CCGCCTGGAC GGGCAAGGCG 180

CCGGTGGTCA ACCGGCCGCT GGTGGCGATC TTTGCCGGCA ACCACGGCGT CACCCGCCAG 240

GGGGTGACCC CGTTCCCGTC ATCCGTCACC GCACAGATGG TCGAGAATTT TGCCGCCGGT 300

GGCGCTGCGA TCAACCAGAT CTGCGTCAGC CACGACCTCG GGCTGAAGGT CTTCGACCTC 360

GCACTCGAAT ACCCGACCGG TGATATCACC GAGGAAGCCG CGCTGTCCGA GCGCGATTGC 420

GCCGCGACCA TGGCCTTTGG CATGGAGGCG ATTGCCGGCG GCACGGATCT TCTGTGCATC 480

GGCGAAATGG GCATCGGCAA CACCACGATC GCGGCCGCGA TCAATCTCGG CCTTTATGGT 540

GGCACGGCCG AAGAATGGGT CGGTCCGGGT ACCGGCTCCG AGGGCGAGGT GCTGAAGCGC 600

AAGATCGCCG CGGTCGAAAA GGCCGTGGCG CTGCATCGCG ATCACCTGTC CGATCCGCTC 660

GAACTGATGC GTCGCCTCGG CGGTCGTGAG ATCGCGGCCA TGGCTGGCGC CATCCTGGCC 720

GCCCGCGTCC AGAAGGTACC TGTCATCATC GACGGCTACG TGGCGACCGC TGCGGCTTCG 780

ATCCTGAAGG CGGCCAACCC GTCGGCCCTC GACCATTGCC TGATCGGCCA TGTTTCGGGC 840

GAACCGGGGC ATCTGCGCGC GATCGAGAAG CTCGGCAAGA CGCCGCTGCT GGCACTCGGC 900

ATGCGGCTTG GCGAAGGCAC GGGCGCGGCC CTTGCCGCCG GTATCGTCAA GGCGGCGGCC 960

GCTTGCCACA GCGGCATGGC GACCTTTGCC CAGGCCGGCG TCAGCAACAA GGAATAG 1017

Met Ser Ala Ser Gly Leu Pro Phe Asp Asp Phe Arg Glu Leu Leu Arg

1 5 10 15

Asn Leu Pro Gly Pro Asp Ala Ala Ala Leu Val Ala Ala Arg Glu Arg

20 25 30

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

35 40 45

Ile Ala Phe Trp Leu Ala Ala Trp Thr Gly Lys Ala Pro Val Val Asn

50 55 60

Arg Pro Leu Val Ala Ile Phe Ala Gly Asn His Gly Val Thr Arg Gln

65 70 75 80

Gly Val Thr Pro Phe Pro Ser Ser Val Thr Ala Gln Met Val Glu Asn

85 90 95

Phe Ala Ala Gly Gly Ala Ala Ile Asn Gln Ile Cys Val Ser His Asp

100 105 110

Leu Gly Leu Lys Val Phe Asp Leu Ala Leu Glu Tyr Pro Thr Gly Asp

115 120 125

Ile Thr Glu Glu Ala Ala Leu Ser Glu Arg Asp Cys Ala Ala Thr Met

130 135 140

Ala Phe Gly Met Glu Ala Ile Ala Gly Gly Thr Asp Leu Leu Cys Ile

145 150 155 160

Gly Glu Met Gly Ile Gly Asn Thr Thr Ile Ala Ala Ala Ile Asn Leu

165 170 175

Gly Leu Tyr Gly Gly Thr Ala Glu Glu Trp Val Gly Pro Gly Thr Gly

180 185 190

Ser Glu Gly Glu Val Leu Lys Arg Lys Ile Ala Ala Val Glu Lys Ala

195 200 205

Val Ala Leu His Arg Asp His Leu Ser Asp Pro Leu Glu Leu Met Arg

210 215 220

Arg Leu Gly Gly Arg Glu Ile Ala Ala Met Ala Gly Ala Ile Leu Ala

225 230 235 240

Ala Arg Val Gln Lys Val Pro Val Ile Ile Asp Gly Tyr Val Ala Thr

245 250 255

Ala Ala Ala Ser Ile Leu Lys Ala Ala Asn Pro Ser Ala Leu Asp His

260 265 270

Cys Leu Ile Gly His Val Ser Gly Glu Pro Gly His Leu Arg Ala Ile

275 280 285

Glu Lys Leu Gly Lys Thr Pro Leu Leu Ala Leu Gly Met Arg Leu Gly

290 295 300

Glu Gly Thr Gly Ala Ala Leu Ala Ala Gly Ile Val Lys Ala Ala Ala

305 310 315 320

Ala Cys His Ser Gly Met Ala Thr Phe Ala Gln Ala Gly Val Ser Asn

325 330 335

Lys Glu

ATGAAAGGTC TGGGAAAAGT GTGCGCGGCC CTCGCGGGTG CGCCCGCCCG GCTTGCGAGA 60

CTCGCCGCAG TCGGCGAGTT TGGCAGCGGC CGGGTCAATG GCCGCAACCT TGGAGGAGCC 120

ATGGGCTTCG TTGGCGATTT CTGTGACGAT GTGGCGCGGT CGATCGGCTT TCTCAGCCGC 180

ATCCCGATGC CTGCGCGTCA TTTCGAAGGT TATGACGGGC GCTTGAGCCG TGCCGTGCGC 240

GCCTTCCCGT TCGCCGGCCT GGCGATCGCA CTGCCATCGG CGGCCGTCGC CATGGCCCTC 300

ATGGCGCTGC AGGTGAGCTC GCTCTTTGCC GCCTTTGTCG TCGTCGCCAT CCAGGCGCTT 360

GTCACCGGCG CACTGCACGA AGACGGGCTT GGCGACACGG CCGATGGCTT TGGCGGCGGT 420

CGCGACCGCG AAGCGGCGCT TGCGATCATG AAGGACAGCC GCATCGGCAC CTATGCGGCC 480

GTCGCCCTCA TCCTCTCCTT CGGCCTGCGC GTCTCGGCGT TCGCCTCGAT CCTGCCGCTC 540

TTTTCGCCGC TGGGCGCCGC CATGGCGATC CTTGGCGCAG CGTGCCTCAG CCGCGCCGCC 600

ATGGTCTGGC ACTGGTCGTC GCTTCCGCCG GCGCGCAGCA GCGGCGTCGC GGCCTCGGCT 660

GGCGAGCCGG AACCGGCGGC CACGCGCTTC GCGCTTGCCT TCGGACTTCT TGTCGCAATG 720

CTGCTCTTCT ATCTCGCGCA GGTCCCGGCG CTCGGCGTCA TCGCGGCGCT CGTCGCATTC 780

CTTGCCACGG TCAAGGGCTT CGCTCGGCTG GCGATGCGCA AGATCGGCGG ACAAACGGGC 840

GACACGATCG GGGCGACGCA GCAACTGACC GAAATCGCCG TGCTCGGTGC CCTTGCGCTG 900

ACGGTTTGA 909

Met Lys Gly Leu Gly Lys Val Cys Ala Ala Leu Ala Gly Ala Pro Ala

1 5 10 15

Arg Leu Ala Arg Leu Ala Ala Val Gly Glu Phe Gly Ser Gly Arg Val

20 25 30

Asn Gly Arg Asn Leu Gly Gly Ala Met Gly Phe Val Gly Asp Phe Cys

35 40 45

Asp Asp Val Ala Arg Ser Ile Gly Phe Leu Ser Arg Ile Pro Met Pro

50 55 60

Ala Arg His Phe Glu Gly Tyr Asp Gly Arg Leu Ser Arg Ala Val Arg

65 70 75 80

Ala Phe Pro Phe Ala Gly Leu Ala Ile Ala Leu Pro Ser Ala Ala Val

85 90 95

Ala Met Ala Leu Met Ala Leu Gln Val Ser Ser Leu Phe Ala Ala Phe

100 105 110

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

115 120 125

Gly Leu Gly Asp Thr Ala Asp Gly Phe Gly Gly Gly Arg Asp Arg Glu

130 135 140

Ala Ala Leu Ala Ile Met Lys Asp Ser Arg Ile Gly Thr Tyr Ala Ala

145 150 155 160

Val Ala Leu Ile Leu Ser Phe Gly Leu Arg Val Ser Ala Phe Ala Ser

165 170 175

Ile Leu Pro Leu Phe Ser Pro Leu Gly Ala Ala Met Ala Ile Leu Gly

180 185 190

Ala Ala Cys Leu Ser Arg Ala Ala Met Val Trp His Trp Ser Ser Leu

195 200 205

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

210 215 220

Pro Ala Ala Thr Arg Phe Ala Leu Ala Phe Gly Leu Leu Val Ala Met

225 230 235 240

Leu Leu Phe Tyr Leu Ala Gln Val Pro Ala Leu Gly Val Ile Ala Ala

245 250 255

Leu Val Ala Phe Leu Ala Thr Val Lys Gly Phe Ala Arg Leu Ala Met

260 265 270

Arg Lys Ile Gly Gly Gln Thr Gly Asp Thr Ile Gly Ala Thr Gln Gln

275 280 285

Leu Thr Glu Ile Ala Val Leu Gly Ala Leu Ala Leu Thr Val

290 295 300

GAGCTCGAAG GGGCTTCCGC CCCGATCGCT GGCGTTAGCC GACGTTCGAC GTGCGGATGA 60

CGCCGAGCGG GCCGAAGGGC GCGTCGACGA CGAGGTTGCG TACGCGCGAC TGGCTGGACG 120

GAACCTTCGA GTTCCAGGCG ATCTGAACGA AATTGGGCTT GCTGAAAATA TACAGCATGG 180

ACATGAACCT TGAGAGGCCG GAGGCCTATC CTCCGGGGCG TGTTGCTATG CCGCTGATAT 240

AGGTGTGCGC TGCAAAAAAT TGAATGCCAA ACTCGCCACG CCATGTCGCA TTCTGGCTAT 300

CGGCCGCGAC ATTTTCGACA AGCCTTGCGA AAGCGCGAAA CAATGCGTGA AAGGGCTTTG 360

TCAATTGCGG CGAAATCGTG TCGAAACAGA CCTTTGCCGC TGCCCGTTTC AGTGTTACCG 420

ATGGCCGCAT GACACGCAGG ATCATGTTGC AGGGAACCGG CTCGGATGTC GGAAAATCGG 480

TATTGGTGGC GGGGCTCTGC CGGCTTGCCG CCAATCAGGG CCTGAAGGTC CGGCCGTTCA 540

AGCCGCAGAA CATGTCGAAC AACGCCGCCG TTTCCGACGA CGGCGGCGAG ATCGGCCGCG 600

CGCAATGGCT GCAGGCGCTG GCCGCGCGCG TGCCGTCGTC GGTGCACATG AACCCGGTGC 660

TCCTGAAGCC GCAGTCGGAC GTGGGCAGCC AGATCGTCGT TCAGGGCAAG GTCGCCGGGC 720

AGGCCAGGGG GCGGGAATAT CAGGCGCTCA AGCCCAAGCT GCTGGGCGCC GTCATGGAGA 780

GTTTCGAACA AATATCGGCC GGTGCCGATC TCGTGGTGGT CGAAGGCGCC GGCTCGCCGG 840

CCGAAATCAA CCTCAGGCCC GGCGACATCG CCAATATGGG CTTTGCGACA CGGGCCAATG 900

TGCCGGTCGT GCTGGTCGGC GACATCGACC GCGGGGGGGT GATCGCCTCG CTGGTCGGCA 960

CGCATGCGAT CCTGCCCGAG GAAGACCGGC GCATGGTGAC CGGCTATCTC ATCAACAAGT 1020

TCCGCGGCGA CGTCACGCTG TTCGACGACG GCATTGCTGC CGTCAACCGC TACACCGGCT 1080

GGCCCTGCTT CGGCGTCGTG CCGTGGCTGA AGGCGGCGGC ACGCCTGCCG GCGGAAGATT 1140

CCGTCGTGCT GGAGAAGCTG ACGCGCGGCG AGGGGCGGGC GCTGAAGGTT GCCGTCCCGG 1200

TACTGTCGCG CATCGCCAAT TTCGACGACC TCGATCCGCT CGCCGCCGAA CCGGAGATTG 1260

ATCTCGTCTT CGTGCGGCCT GGCAGTCCCA TTCCGGTCGA CGCTGGCCTC GTCGTCATTC 1320

CCGGGTCGAA ATCGACCATC GGCGACCTCA TCGATTTCCG TGCGCAAGGG TGGGACCGTG 1380

ACCTCGAACG TCATGTGCGC CGGGGCGGCC GGGTCATCGG CATCTGCGGC GGCTACCAGA 1440

TGCTCGGCCG GCGCGTCACC GATCCGCTCG GCATCGAGGG CGGCGAACGT GCGGTCGAGG 1500

GCCTCGGGCT GCTCGAGGTC GAGACCGAGA TGGCGCCGGA AAAGACGGTG CGCAACAGCC 1560

GCGCCTGGTC GCTGGAGCAT GATGTGGTGC TCGAAGGCTA CGAAATCCAT CTTGGCAAGA 1620

CGCAAGGTGC GGACTGTGGC CGGCCGTCGG TGCGCATCGA CAATCGCGCC GACGGCGCCC 1680

TTTCGGCCGA TGGCCGCGTG ATGGGCACCT ACCTGCATGG GCTCTTCACC AGCGACGCCT 1740

ATCGCGGCGC GCTGCTCAAG AGTTTCGGCA TCGAAGGCGG CGCCAACAAC TACCGCCAAT 1800

CGGTCGATGC GGCGCTCGAC GATGTCGCGA ACGAACTGGA GGCTGTGCTC GATCGTCGCT 1860

GGCTGGACGA GTTGCTCAGG CACTAGGGAC GCGGCAACGG TCAGCCAGCA GGTCCGGTAC 1920

GTCGGGCCCA ACAGGAGCAA CGAGCTTATC CGACGGAACT ACGCTGCGAC ATCGTGCTCC 1980

TCGCTTGCGG CTTCCCAGAC TTCCCGCGCG GCATCCAGGT TCATCAGGGC AATCCCCAGG 2040

CCGACGATCA GGTCCGGCCA GGCCGACTGC CACAGATAGG CTGTCGCCAG ACCCGCGGCG 2100

ATGATGGCCA CATTGGCGAA GGCATCGTTG CGGGCCGAGA GAAATGCTGC CCGCGTGAGC 2160

GTGCCGCTCG TGTGACGGTA GGCGACGAGC AGATAGGCGC AGAAGAGGTT GACCACCAGC 2220

GCCCCAAGTC CGGTCAGGGA CAGGGCAAAG GGCTCTGGCG GGACCGGATC CATGAACTTC 2280

GCCCAGGCCG TCCAAAGGAA GGCCAGCGCC GGTACCAGTA GAATGAACGC CATCGCCATG 2340

CCGACCCGCG CGCGGGTTCG CGCCGTCCAG GCCAGAGCAA AGAAAATCAG CATGTTGACG 2400

GAGGCGTCTT CGAGGAAGTC GACGCTGTCG GCCATGAGGG ACACCGAGCC GATCGAAAGC 2460

GCGACAAGGA GTTCGACCCC GAAATAGCCA AGGTTCAACA GGGAGACGAT GAGGACGACG 2520

CGGCGCAGGT CGGTATCCAC TCGAAAGGTT CCCTTTCTGG CGAGATTCGC CCTCGGCACT 2580

TTTTTTGGCG AGATTCGCCC TCGGCACTTT GGCACAGGTG TTAGCAGCAG TTTGCTATCC 2640

ATAGCACTAG GTTTCGACAT CGGTTCCGTT CACACTGCCG TCGTGCCTGA CGCCCGACAA 2700

ATCGTCGCGT GGCGCAACTC GGCCGGGGAG GCGTCGCATG CGTCGATTGA CTTTGGGCTG 2760

CCCGCTTCCT AATCATCAGG TGTTGGATGG TTCCCCCTTG TCGTGGCGAT CTGGGGGAAT 2820

AATTGGGAAT GTGACGGATG GACCCAAATC GGGCATCCTT ATCGCAGCCG ACCCCGCGAC 2880

TGTAGAACGG TCAGGGTTCG CCATCGGGAT TGGTGCCGGG CTGTCGGCCG GTTGCATGGG 2940

CAATCGGGGC AGGTCGGGGA TCAAGCCGGA AAAGCCACTG GCGTGGCATC GTGATCAGCC 3000

GGGTTTGGAC GCCTCTTCTT CTACGAATCG TCCGCCTTTC ACGATGTCCC TCACAGCGCC 3060

CATGCGTCGG AGACGACGCG CAAAGGTTCG CTGTGGCACC GGAAAGACGC CGGGAAGGTG 3120

AGGCGGGCCG CTCGGGCCCT GACATCGGAA CCTTGCCGTT TAAGGGCGAG GCGATGTTCG 3180

GCCCGTGACG CCGTGAGCCA GGAGACCTGC CATCCGGCAT GGGCATTCCG CCCGAGGGGA 3240

CTTTTGTCTC CAACGCCATC ACGGAGGTTG TTTTGGCTCG CAGATGTTTT CAAGAACGCG 3300

CCCGTGGCGC GTCCGATGGC TTTTGCCACC GACGGCTGAT TTGGGAATGT TGAGGCAGCC 3360

ACGATGAGCA GTCTCAGCGC CGGGCCCGTG CTGGTCCTTG GCGGCGCCCG TTCCGGCAAG 3420

TCCAGCTTTT CCGAGAGGCT CGTCGAAGCG TCCGGCTTCA CCATGCATTA TGTCGCCACG 3480

GGCCGCGCCT GGGACGACGA AATGCGCGAG CGCATCGACC ATCACCGGAC GCGCCGCGGC 3540

GAGGGCTGGA CGACGCATGA GGAGCCGCTC GATCTCGTCG GCATCCTCAG ACGCATCGAT 3600

GATCCCAGCC ATGTGGTCCT GATCGACTGC CTGACGCTAT GGGTCACCAA TCTCATGCTG 3660

GAAGAGCGCG ACATGACGGC GGAGTTCGCC GCCCTTGTTG CGTATCTGCC CGAGGCGCGG 3720

GCGCGCCTCG TCTTTGTTTC CAATGAGGTC GGCCTCGGCA TCGTGCCCGA GAACCGCATG 3780

GCCCGCGAGT TTCGCGACCA TGCCGGCCGG CTTCACCAGA TCGTTGCGGA GAAATCCGCT 3840

GAAGTTTACT TTGTCGCGGC CGGTTTGCCG CTGAAAATGA AGGGTTGATC CATGACCACT 3900

GCGAGAGCCA ACCAGGGCAA GATCCCGGCG ACCGTCATCA CCGGCTTCCT CGGCGCCGGC 3960

AAGACGACGA TGATCCGCAA CCTGCTGCAG AACGCCGACG GCAAGCGCAT CGGCCTGATC 4020

ATCAACGAGT TCGGCGATCT TGGCGTCGAC GGCGATGTCT TGAAGGGCTG CGGTGCCGAG 4080

GCCTGCACCG AGGACGACAT CATCGAGCTC ACCAATGGCT GCATCTGCTG CACCGTGGCT 4140

GACGATTTCA TCCCGACCAT GACGAAGCTG CTCGAGCGTG AAAACCGTCC TGACCACATC 4200

ATCATCGAAA CCTCGGGCCT TGCCCTGCCG CAGCCGCTGA TCGCCGCTTT CAACTGGCCG 4260

GATATCCGCA GCGAAGTGAC CGTCGATGGC GTCGTCACCG TGGTCGACAG CGCCGCCGTT 4320

GCCGCTGGCC GCTTTGCCGA CGACCACGAC AAGGTCGATG CGCTGCGCGT CGAGGACGAC 4380

AATCTCGATC ACGAAAGCCC GATCGAGGAG CTGTTCGAGG ATCAACTGAC GGCTGCCGAT 4440

CTCATCGTTC TCAACAAGAC CGATCTGATC GATGCCTCCG GCCTCAAGGC CGTGCGCGAC 4500

GAGGTGTCTT CGCGCACCAG CCGCAAGCCC ACGATGATCG AGGCGAAAAA CGGCGAAGTC 4560

GCCGCTGCCA TCCTGCTTGG CCTCGGTGTC GGCACGGAAA GCGATATCGC CAACCGCAAG 4620

TCGCATCACG AGATGGAGCA CGAGGCAGGT GAGGAGCACG ATCACGACGA GTTCGACAGC 4680

TTCGTCGTCG AGCTCGGTTC GATCGCCGAT CCGGCCGCCT TCATCGATCG CCTGAAGGGC 4740

GTAATCGCGG AGCACGACGT TCTGCGCCTC AAGGGTTTTG CAGACGTGCC CGGCAAGCCG 4800

ATGCGCCTCC TGATCCAGGC GGTCGGCGCC CGCATCGACC AATATTACGA CCGCGCCTGG 4860

GGCGCTGGCG AAAAGCGCGG TACGCGCCTC GTCGTCATCG GCCTGCACGA CATGGACGAG 4920

GCGGCGGTGC GCGCCGCGAT CACCGCGCTC GTGTAGATCG TTCTTTGAAT GAAATGATCT 4980

AACGCATTGA AATGATGCAG TTCCGGATGG AGAACGCTTT TAGCGTTTTC GTTCGGAATT 5040

GCCCCAACGG ACAAGACGAA TGCATCTGCT TCTCGCCCAG AAAGGAACGA TCGCCGACGG 5100

CAACGAGGCG ATCGACCTTG GGCAAACGCC GGCCGATATC CTTTTCCTAT CGGCCGCCGA 5160

CACCGAGCTC TCCTCGATCG CCGCGGCTCA CGGCCGACGC GACGGAGGCT TGAGCCTGCG 5220

CATCGCCAGC CTGATGAGCC TGATGCACCC GATGTCGGTC GACACTTACG TCGAGCGCAC 5280

GGCGCGTCAC GCCAAGCTGA TCGTCGTCCG GCCGCTCGGT GGCGCCAGCT ATTTCCGTTA 5340

TCTGCTGGAA GCCCTGCATG CGGCTGCCGT CACCCATCGT TTCGAGATCG CGGTTCTGCC 5400

GGGTGACGAC AAGCCGGATC CGGGGCTGGA GCCTTTCTCC ACCGTCGCAG CCGACGACCG 5460

CCAGCGCCTT TGGGCTTACT TCACCGAAGG CGGCTCGGAC AATGCCGGGC TGTTTCTCGA 5520

CTATGCGGCC GCACTGGTCA CAGGTGCGGA GAAGCCGCAG CCGGCAAAGC CCCTGTTGAA 5580

GGCCGGCATC TGGTGGCCGG GTGCTGGTGT GATCGGCGTC AGCGAATGGC AGTCCCTTGT 5640

TCAGGGACGG ATGGTAGCGA GGGAGGGATT CGAACCCCCG ACGGTCGGGA TCTGCTTTTA 5700

CCGCGCGCTC GTGCAGAGTG GCGAGACACG GCCTGTGGAG GCGCTGATCG ATGCGCTGGA 5760

GGCTGAAGGT GTGCGGGCAC TGCCGGTGTT TGTCTCAAGC CTCAAGGATG CCGTTTCCGT 5820

CGGCACGCTG CAGGCGATTT TTTCCGAGGC CGCACCCGAC GTGGTGATGA ACGCCACTGG 5880

CTTTGCGGTC TCGTCGCCCG GTGCCGACCG TCAGCCGACG GTGCTGGAAT CGACCGGTGC 5940

GCCGGTGCTG CAGGTGATTT TCTCCGGCTC GTCGCGGGCG CAATGGGAAA CGTCGCCGCA 6000

GGGGCTGATG GCGCGCGACC TCGCCATGAA CGTGGCACTC CCCGAAGTCG ATGGCCGCAT 6060

CCTTGCGCGC GCCGTCTCCT TCAAGGCGGC GTCGATCTAT GACGCCAAGG TGGAGGCCAA 6120

TATCGTCGGC CATGAGCCGC TCGAAGGCCG GGTGCGCTTT GCCGCTGATC TTGCCGTCAA 6180

CTGGGCGAAC GTGCGCCGGG CAGAGCCCGC CGAGCGCCGT ATTGCCATCG TCATGGCCAA 6240

CTATCCGAAC CGCGACGGTC GCCTCGGCAA CGGTGTCGGG CTCGACACGC CGGCCGGTAC 6300

CGTCGAGGTG CTTAGCGCCA TGGCGCGGGA AGGCTATGCG GTCGGTGAGG TTCCCGCCGA 6360

TGGCGACGCG CTGATCCGCT TTCTGATGGC CGGGCCGACC AATGCGGCGA GCCATGACCG 6420

TGAAATCCGC GAGCGTATTT CGCTGAACGA TTACAAAACG TTCTTCGATT CGCTTCCGAA 6480

ACAGATAAAG GATGAAGTTG CCGGTCGCTG GGGCGTGCCG GAGGCCGATC CCTTTTTCCT 6540

CGATGGCGCC TTCGCGCTGC CGCTCGCCCG CTTCGGCGAG GTGATCGTCG GCATCCAACC 6600

GGCGCGCGGC TACAACATCG ATCCGAAGGA AAGCTACCAT TCCCCGGACC TCGTGCCGCC 6660

GCATGGCTAT CTCGCCTTCT ACGCCTTCCT GCGCCAGCAG TTCGGAGCGC AGGCGATCGT 6720

CCACATGGGC AAGCACGGCA ATCTCGAATG GCTGCCGGGC AAGGCGCTGG CGCTGTCGGA 6780

AACCTGCTAT CCCGAAGCGA TCTTCGGGCC GCTGCCGCAC ATCTATCCCT TCATCGTCAA 6840

CGATCCGGGC GAAGGTACGC AGGCCAAGCG CCGCACCAGC GCCGTCATCA TCGACCACCT 6900

GACCCCGCCC TTGACGCGCG CCGAATCCTA CGGCCCGCTC AAGGATCTGG AAGCGCTCGT 6960

CGACGAATAT TACGACGCCG CCGGCGGTGA TCCGCGCCGC CTCAGGCTGC TCAGCCGCCA 7020

GATCCTCGAT CTCGTGCGCG ACATCGGCCT CGACAGCGAC GCAGGCATCG ACAGGGGCGA 7080

CAGCGACGAC AAGGCGCTGG AAAAGCTCGA CGCCTATCTC TGCGACCTCA AGGAAATGCA 7140

GATCCGCGAC GGCCTGCACA TCTTCGGCGT TGCGCCGGAA GGGCGGTTGT TGACGGACCT 7200

CACCGTAGCG CTGGCGCGCG TGCCCCGAGG TCTCGGCGAG GGCGGCGACC AGAGCCTGCA 7260

GCGGGCGATC GCAGCGGATG CGGGGCTGCG TGGGTTTGCT ATTCCCACCT CGGCGGGGGG 7320

CAACCCCGCA CGCGACGCCC AACCCTTCGA CCCGCTCGAC TGCGTCATGT CCGACACCTG 7380

GACAGGCCCG AAACCGTCCA TCCTCGCTGA CCTCTCGGAC GCCCCCTGGC GCACCGCCGG 7440

CGATACGGTC GAGCGCATCG AGTTGCTTGC CGCAAATCTC GTGTCGGGTG AACTGGCTTG 7500

CCCGGACCAC TGGGCCAACA CCCGCGCCGT GCTCGGCGAA ATCGAAACGC GCCTGAAGCC 7560

GTCGATTTCA AACTCGGGTG CCGCCGAGAT GACCGGCTTC CTCACCGGTC TCAGCGGCCG 7620

CTTCGTCGCC CCCGGTCCAT CGGGCGCGCC GACGCGCGGC CGGCCGGATG TGTTGCCGAC 7680

GGGGCGCAAT TTCTACTCGG TCGACAGCCG CGCCGTGCCG ACGCCGGCGG CTTACGAGCT 7740

TGGCAAGAAA TCGGCCGAGC TTCTGATCCG CCGCTACCTG CAGGACCATG GCGAATGGCC 7800

GTCCTCCTTT GGCCTGACCG CCTGGGGCAC GGCGAACATG CGCACCGGCG GCGACGACAT 7860

CGCCCAGGCC CTGGCGCTGA TCGGCGCCAA GCCCACCTGG GACATGGTCT CTCGCCGGGT 7920

GATGGGCTAC GAGATCGTGC CGCTCGCAGT CCTCGGCCGC CCACGCGTCG ACGTGACCTT 7980

GCGCATTTCC GGCTTCTTCC GCGATGCCTT CCCGGACCAG ATCGCGCTCT TCGACAAGGC 8040

GATCCGCGCC GTCGCGCTGG AGGAAGACGA TGCCGACAAC ATGATCGCCG CACGCATGCG 8100

GGCGGAAAGC CGGCGGCTGG AGGCCGAAGG CGTGGAAGCC GCCGAGGCCG CGCGTCGCGC 8160

CTCCTACCGC GTCTTTGGCG CAAAGCCCGG TGCCTATGGC GCCGCCCTGC AGGCGCTGAT 8220

CGACGAGAAG GGCTGGGAAA CCAAAGCAGA TCTCGCCGAG GCCTATCTTA CCTGGGGCGC 8280

CTATGCCTAT GGCGCCGGCG AGGAGGGCAA GGCCGAGCGC GATCTTTTCG AGGAGCGCCT 8340

GCGCACGATA GAGGCGGTGG TGCAGAACCA GGACAACCGC GAGCACGATC TGCTCGACAG 8400

CGACGACTAC TACCAGTTCG AAGGCGGCAT GAGCGCTGCC GCCGAACAGC TCGGCGGTCA 8460

CCGTCCGGCG ATCTACCACA ACGACCATTC CCGTCCGGAA AAGCCTGTGA TCCGGTCGCT 8520

CGAAGAAGAG ATCGGCCGCG TGGTCCGGGC CCGCGTCGTC AATCCCAAGT GGATCGATGG 8580

CGTCATGCGC CACGGATACA AGGGCGCCTT CGAGATCGCT GCCACGGTCG ACTACATGTT 8640

CGCCTTTGCC GCGACCACGG GTGCGGTGCG CGACCATCAT TTCGAGGCCG CTTATCAGGC 8700

GTTCATTGTC GACGAGCGCG TGGCTGACTT CATGCGCGAC AAGAACCCGG CCGCCTTTGC 8760

CGAGCTTGCC GAACGCCTGC TTGAAGCAAT CGACCGCAAT CTCTGGACGC CGCGCTCGAA 8820

TTCGGCGCGG TTTGAACTTG CCGGCATCGG CACGGCAGCA ACCCGGCTTC GTGCCGGCAA 8880

TGAATAGAGC GGTTCCGGGC TGGCGGTTAT CCGTCCGGAA TTGCTTGGAA ACAAAGACCT 8940

GGTTCCGTTT CGCTGCTCAG TGAAGTGCGA AAAGGAACCG AAGCGGGACG AGGGCGTCTG 9000

CCCATCCCGA ACTTGAGAAC TGAGGGAGTG ATCATGAGCG ACGAGACGAC AGTAGGCGGC 9060

GAAGCCCCGG CCGAGAAGGA CGATGCCCGC CACGCCATGA AGATGGCGAA GAAGAAGGCA 9120

GCACGCGAAA AGATCATGGC GACGAAGACC GACGAGAAGG GTCTGATCAT CGTCAACACC 9180

GGCAAAGGCA AGGGCAAGTC GACCGCCGGC TTCGGCATGA TCTTCCGCCA TATCGCCCAC 9240

GGCATGCCCT GCGCCGTCGT GCAGTTCATC AAGGGTGCGA TGGCAACCGG CGAGCGCGAG 9300

TTGATCGAGA AGCATTTCGG CGATGTCTGC CAGTTCTACA CGCTCGGCGA GGGCTTCACC 9360

TGGGAAACGC AGGATCGCGC CCGCGATGTT GCGATGGCTG AAAAGGCCTG GGAGAAGGCG 9420

AAGGAACTGA TCCGTGACGA GCGCAACTCG ATGGTGCTGC TCGACGAGAT CAACATTGCT 9480

CTGCGCTACG ACTACATCGA CGTCGCCGAA GTGGTGCGCT TCCTGAAGGA AGAAAAGCCG 9540

CACATGACGC ATGTGGTGCT CACCGGCCGC AACGCGAAAG AAGACCTGAT CGAAGTCGCC 9600

GATCTCGTCA CTGAGATGGA GCTGATCAAG CATCCGTTCC GTTCCGGCAT CAAGGCGCAG 9660

CAGGGCGTGG AGTTCTGATG AGCCAGAGCT GGCAGTTCTG GGCGCTGCTT TCGGCCGCCT 9720

TCGCTGCGCT CACGGCGGTG TTTGCCAAGG TCGGGGTTGC GCAGATCAAC TCCGACTTCG 9780

CAACGCTGAT CCGCACCGTC GTCATCCTCT GCGTGATCGC CGCCATCGTG GCGGCGACAG 9840

GGCAGTGGCA GAAGCCATCG GAAATCCCGG GCCGCACCTG GCTGTTCCTG GCGCTGTCAG 9900

GGCTTGCGAC TGGCGCTTCC TGGCTTGCCT ATTTCCGCGC GCTGAAGCTC GGCGACGCCG 9960

CCCGCGTGGC GCCGCTCGAC AAGCTCTCGA TCGTCATGGT CGCGATCTTC GGCGTGCTCT 10020

TCCTCGGTGA AAAGCTCAAC CTGATGAACT GGCTCGGCGT CGCCTTCATT GCCGCCGGGG 10080

CGCTGTTGCT GGCGGTGTTT TGAGCGCGCC TGCTCTGGTG CCTGTTCACT GAATGCTCGC 10140

CTCAATCAAT CCGTAATCCC GACACATGCA GTGGTTGTGA CGAGCGGGAG GACGGCATGC 10200

AGATTGAAGG CAATTGGAGC GAGCGCCTTC CTGATCCGTC GGGCCACGTC GCGCAGTTCG 10260

GCAGACGCTG GAAGCGTCGC AGCCTGAGGG TGAGCCCTGC TTCAGACCCA CCGGCGGACA 10320

CGCCTGCAAT AGGCACCGTA GGCGTCGCCG AAGACCTTGG CGAGGTGGGT TTCCTCCATG 10380

CGGATCTGGT AGGAAATCGA GATCCAGGCG GAGAGCGCCA GCGCCACCGA GATGACGTTG 10440

GGCACCGCCA TCACCGTGCC GATCAGCGCG GTCACCATGC CGACATAGAT CGGGTTGCGC 10500

GAGAAGGCAT AGAGGCCTGA GGTCACAAGC GGCGCGTCCT GCTTTTCAGG GATGCCGATC 10560

TTCCAGGAAT GACGCATCGC CCATTGCGAC AGCATCGTCA GCCCGCCGCC GAGCGTCATC 10620

AGCGCCAGGC CGACGGCGTG AAGGATGGGC GTGTCGAGCG CCGGGATCCG GCCGAGGGCA 10680

GCATCGACGG AGGCCGGGAG CATGGCGACC GCCAGCAGGT GGATCACCAG CGCTGCGACG 10740

ATCAGGCGGA AAAGCCTGCC CGCAAACCCT TCCGCATCGT CGCCATAGGT TAGCACGACC 10800

GGCGAGCGGC CGGATTGCAC GCGGCGGAGG ATCGCCAGCG CGAGCGTGGA CAATCCCACG 10860

ACGAGCATCA GGATGGTGGG AAGGGTGGTG GACATGGAAA CCTCTGGAGC GAGCTGACAA 10920

GACAGGAGCG CACGACGGGT AGGCGGCCCA TATGAGCGTC TACCCGGCGA AGCATTCTGA 10980

TCACCTTGCA ATCTCTAGTA ACTAGAGGTT CAAGCGTCGG ACCTGTCCGA CTTTCGTCGT 11040

GGTTACCGGA TCTTATTGCC AAGCGTTGGA GGCTGTCATC GTCGCCCCCG CCGTGTCGGA 11100

AGGTCGGCAA AATTCGTCTC TTGACGGCTG CTCCTTCCGT CGAGCGATTG CATAGGCAGG 11160

AGGCCGCACC CATGTTAGAC CGTCGACAGG CTAAATACGG GTGAACCTTG AAGAATACTC 11220

TCAGAGCTGC GGTTGGTGTC GCATCGGTCT TGCTGTTCTT GTCATCAGGT GTGGCGGGGC 11280

AGGCGCAAAC CGTGAAGAGC GGGGCGTCAC GAGCTCAAGA AACGACGACC ACCCAGAAGG 11340

CGAAACCGAA AACTAAAACG ACGCGCAAGC AAAGGGCTGC GGATGAAGCC AAGGCCAAGG 11400

CGCTCGCCGA AGCGCGCCGT CCACGGATTT GCAAGACGCG GGAGAGCGAA TGCAGCTATG 11460

GCGCAGGTCC GGTCGGAGAG CAGTGCTCGT GCTGGTCGAA ATCCGGTGCG CCTGATCTTG 11520

GCATAACTGT CAGGCGTTGA CCGCCCGCGA CCTTCGCGCG GGCAGGCAAG CGTGCGTCGC 11580

TCGAAGCGAC GCCTGACGCG ATAGAAATCA CGGGTCGCCT GGTTCGTTCT GAAAGCTTGG 11640

GATTGGGTTT AGGTGATGGA AGCCGGCGTT GAACGCAAAA TAATGATCGA TCTCGAGAAC 11700

AGCGCGCTCC AGTTTGCAAC CCGAGCACAC GGCGAACAGA AGCGTAAGTA TGACGGTCGG 11760

CCCTATATCG TTCATCCGAT TGCGGTGGCG GAGATTGTTC GAAGCGTGCC CCATACGCCC 11820

GAAATGATCG CCGCAGCGCT GCTTCACGAT ACGGTCGAAG ATACCGACGC GACGCTGCTG 11880

GAGATCAAGG AAGCGTTCGG CCCCAAGGTC GCAACACTGG TTGCGTGGCT CACCGACATA 11940

TCCACTCCGT TCCACGGCAA CCGACAGGTG CGCAAGGAAC TGGATCGCCA GCACCTCGCA 12000

TCGGCGCCCG CCGCGGCGAA AACCGTCAAG CTCGCCGACC TGATCGACAA TGCGATAGCG 12060

ATCAAAGCCG GCGATCCGAA TTTCTGGAAA GTGTTCGGCG CCGAGATGAA ACGCTTGCTG 12120

GAGGTCTTGG GCGACGGCGA CGAGACCCTT CTCGCAAAGG CCCGTGCATT AGCGCCGGAA 12180

TGAGAGTGCC GCCGTTTATC GGCAAGCATG TCTGTGCCAT GTCGACCCGG TCAACCGGTC 12240

ATCCAAGATC GCAGAACGGA CATGCATTTG CGGTTTTGCC CGCCGGTGTG GCCCAGCCAC 12300

GCCTCACAGG CTGCGCGGTT GCGGCCGTTA GGACAGCGCA GAATTTGCCG ACCGCGCCGC 12360

GCCTCAATGC CCCAGCCAGA TCCGCAAGGG ATGCGTCGGA TCTGCGAGCA GCCGGATCGC 12420

GAGCGCGATC GAGACGATGA CGAGCAGCGG CTTGATGATC TTGGCGCCCT TGGCCATGGC 12480

ATAGCGCGAG CCGACCTGGG CGCCGAGGAA CTGGCCGAGG CCCATCAACA GGCCGACCTT 12540

CCAGAGAACG GCGCCGAAGA AGAGGAAGAC GCCGAAGGCG CCGACGTTGG AGCCAAAGTT 12600

GAGGAACTTC GTGTGCGCCG TCGCCTTCAA CACGCCGAAG CCGGCGAGGG TAACGAAGCC 12660

GAGCATGAAG AACGAGCCGG TGCCGGGGCC GAAGACGCCG TCATAAAAGC CGATTAGCGG 12720

CACCAGTGTC AGCGTGAAGA CGAAGGGGGT GACGCGGCTG TGCTGGTCGA CGTCGCCCAT 12780

GTTCGGCTTC AGGCCGAAAT AAAGCGCAAT GGCGATCAGC AGAAAGGGCA GGATCGCCTT 12840

CAGCACGTCG CCGGGAACGA TGGTTGCGAG CAGGGCGCCG AGCACGGCGC CGGCGGCCGA 12900

CATCAGCGCC ATCGGCAGCT GCTCTTTCAG GTTCACGTGG CCGCGCCGGG CATAGGACAG 12960

CGTGGCCGAG CCGGAGCCGA ACAATCCCTG CAGCTTGTTG GTGCCGAGCG TCTGCAAGGG 13020

CGGGATGCCC GCAATGAGCA TGGCCGGAAT GGTGATCATG CCACCGCCGC CGGCGATCGA 13080

ATCGATGAAG CCTGCGATGA AGGCGGCGAC GAACAGGAAG GCGAGCAGGT GGAAGGCGAG 13140

ATCT 13144

ATGACACGCA GGATCATGTT GCAGGGAACC GGCTCGGATG TCGGAAAATC GGTATTGGTG 60

GCGGGGCTCT GCCGGCTTGC CGCCAATCAG GGCCTGAAGG TCCGGCCGTT CAAGCCGCAG 120

AACATGTCGA ACAACGCCGC CGTTTCCGAC GACGGCGGCG AGATCGGCCG CGCGCAATGG 180

CTGCAGGCGC TGGCCGCGCG CGTGCCGTCG TCGGTGCACA TGAACCCGGT GCTCCTGAAG 240

CCGCAGTCGG ACGTGGGCAG CCAGATCGTC GTTCAGGGCA AGGTCGCCGG GCAGGCCAGG 300

GGGCGGGAAT ATCAGGCGCT CAAGCCCAAG CTGCTGGGCG CCGTCATGGA GAGTTTCGAA 360

CAAATATCGG CCGGTGCCGA TCTCGTGGTG GTCGAAGGCG CCGGCTCGCC GGCCGAAATC 420

AACCTCAGGC CCGGCGACAT CGCCAATATG GGCTTTGCGA CACGGGCCAA TGTGCCGGTC 480

GTGCTGGTCG GCGACATCGA CCGCGGGGGG GTGATCGCCT CGCTGGTCGG CACGCATGCG 540

ATCCTGCCCG AGGAAGACCG GCGCATGGTG ACCGGCTATC TCATCAACAA GTTCCGCGGC 600

GACGTCACGC TGTTCGACGA CGGCATTGCT GCCGTCAACC GCTACACCGG CTGGCCCTGC 660

TTCGGCGTCG TGCCGTGGCT GAAGGCGGCG GCACGCCTGC CGGCGGAAGA TTCCGTCGTG 720

CTGGAGAAGC TGACGCGCGG CGAGGGGCGG GCGCTGAAGG TTGCCGTCCC GGTACTGTCG 780

CGCATCGCCA ATTTCGACGA CCTCGATCCG CTCGCCGCCG AACCGGAGAT TGATCTCGTC 840

TTCGTGCGGC CTGGCAGTCC CATTCCGGTC GACGCTGGCC TCGTCGTCAT TCCCGGGTCG 900

AAATCGACCA TCGGCGACCT CATCGATTTC CGTGCGCAAG GGTGGGACCG TGACCTCGAA 960

CGTCATGTGC GCCGGGGCGG CCGGGTCATC GGCATCTGCG GCGGCTACCA GATGCTCGGC 1020

CGGCGCGTCA CCGATCCGCT CGGCATCGAG GGCGGCGAAC GTGCGGTCGA GGGCCTCGGG 1080

CTGCTCGAGG TCGAGACCGA GATGGCGCCG GAAAAGACGG TGCGCAACAG CCGCGCCTGG 1140

TCGCTGGAGC ATGATGTGGT GCTCGAAGGC TACGAAATCC ATCTTGGCAA GACGCAAGGT 1200

GCGGACTGTG GCCGGCCGTC GGTGCGCATC GACAATCGCG CCGACGGCGC CCTTTCGGCC 1260

GATGGCCGCG TGATGGGCAC CTACCTGCAT GGGCTCTTCA CCAGCGACGC CTATCGCGGC 1320

GCGCTGCTCA AGAGTTTCGG CATCGAAGGC GGCGCCAACA ACTACCGCCA ATCGGTCGAT 1380

GCGGCGCTCG ACGATGTCGC GAACGAACTG GAGGCTGTGC TCGATCGTCG CTGGCTGGAC 1440

GAGTTGCTCA GGCACTAG 1458

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

1 5 10 15

Ser Val Leu Val Ala Gly Leu Cys Arg Leu Ala Ala Asn Gln Gly Leu

20 25 30

Lys Val Arg Pro Phe Lys Pro Gln Asn Met Ser Asn Asn Ala Ala Val

35 40 45

Ser Asp Asp Gly Gly Glu Ile Gly Arg Ala Gln Trp Leu Gln Ala Leu

50 55 60

Ala Ala Arg Val Pro Ser Ser Val His Met Asn Pro Val Leu Leu Lys

65 70 75 80

Pro Gln Ser Asp Val Gly Ser Gln Ile Val Val Gln Gly Lys Val Ala

85 90 95

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

100 105 110

Gly Ala Val Met Glu Ser Phe Glu Gln Ile Ser Ala Gly Ala Asp Leu

115 120 125

Val Val Val Glu Gly Ala Gly Ser Pro Ala Glu Ile Asn Leu Arg Pro

130 135 140

Gly Asp Ile Ala Asn Met Gly Phe Ala Thr Arg Ala Asn Val Pro Val

145 150 155 160

Val Leu Val Gly Asp Ile Asp Arg Gly Gly Val Ile Ala Ser Leu Val

165 170 175

Gly Thr His Ala Ile Leu Pro Glu Glu Asp Arg Arg Met Val Thr Gly

180 185 190

Tyr Leu Ile Asn Lys Phe Arg Gly Asp Val Thr Leu Phe Asp Asp Gly

195 200 205

Ile Ala Ala Val Asn Arg Tyr Thr Gly Trp Pro Cys Phe Gly Val Val

210 215 220

Pro Trp Leu Lys Ala Ala Ala Arg Leu Pro Ala Glu Asp Ser Val Val

225 230 235 240

Leu Glu Lys Leu Thr Arg Gly Glu Gly Arg Ala Leu Lys Val Ala Val

245 250 255

Pro Val Leu Ser Arg Ile Ala Asn Phe Asp Asp Leu Asp Pro Leu Ala

260 265 270

Ala Glu Pro Glu Ile Asp Leu Val Phe Val Arg Pro Gly Ser Pro Ile

275 280 285

Pro Val Asp Ala Gly Leu Val Val Ile Pro Gly Ser Lys Ser Thr Ile

290 295 300

Gly Asp Leu Ile Asp Phe Arg Ala Gln Gly Trp Asp Arg Asp Leu Glu

305 310 315 320

Arg His Val Arg Arg Gly Gly Arg Val Ile Gly Ile Cys Gly Gly Tyr

325 330 335

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

340 345 350

Glu Arg Ala Val Glu Gly Leu Gly Leu Leu Glu Val Glu Thr Glu Met

355 360 365

Ala Pro Glu Lys Thr Val Arg Asn Ser Arg Ala Trp Ser Leu Glu His

370 375 380

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

385 390 395 400

Ala Asp Cys Gly Arg Pro Ser Val Arg Ile Asp Asn Arg Ala Asp Gly

405 410 415

Ala Leu Ser Ala Asp Gly Arg Val Met Gly Thr Tyr Leu His Gly Leu

420 425 430

Phe Thr Ser Asp Ala Tyr Arg Gly Ala Leu Leu Lys Ser Phe Gly Ile

435 440 445

Glu Gly Gly Ala Asn Asn Tyr Arg Gln Ser Val Asp Ala Ala Leu Asp

450 455 460

Asp Val Ala Asn Glu Leu Glu Ala Val Leu Asp Arg Arg Trp Leu Asp

465 470 475 480

Glu Leu Leu Arg His

ATGAGCAGTC TCAGCGCCGG GCCCGTGCTG GTCCTTGGCG GCGCCCGTTC CGGCAAGTCC 60

AGCTTTTCCG AGAGGCTCGT CGAAGCGTCC GGCTTCACCA TGCATTATGT CGCCACGGGC 120

CGCGCCTGGG ACGACGAAAT GCGCGAGCGC ATCGACCATC ACCGGACGCG CCGCGGCGAG 180

GGCTGGACGA CGCATGAGGA GCCGCTCGAT CTCGTCGGCA TCCTCAGACG CATCGATGAT 240

CCCAGCCATG TGGTCCTGAT CGACTGCCTG ACGCTATGGG TCACCAATCT CATGCTGGAA 300

GAGCGCGACA TGACGGCGGA GTTCGCCGCC CTTGTTGCGT ATCTGCCCGA GGCGCGGGCG 360

CGCCTCGTCT TTGTTTCCAA TGAGGTCGGC CTCGGCATCG TGCCCGAGAA CCGCATGGCC 420

CGCGAGTTTC GCGACCATGC CGGCCGGCTT CACCAGATCG TTGCGGAGAA ATCCGCTGAA 480

GTTTACTTTG TCGCGGCCGG TTTGCCGCTG AAAATGAAGG GTTGA 525

Met Ser Ser Leu Ser Ala Gly Pro Val Leu Val Leu Gly Gly Ala Arg

1 5 10 15

Ser Gly Lys Ser Ser Phe Ser Glu Arg Leu Val Glu Ala Ser Gly Phe

20 25 30

Thr Met His Tyr Val Ala Thr Gly Arg Ala Trp Asp Asp Glu Met Arg

35 40 45

Glu Arg Ile Asp His His Arg Thr Arg Arg Gly Glu Gly Trp Thr Thr

50 55 60

His Glu Glu Pro Leu Asp Leu Val Gly Ile Leu Arg Arg Ile Asp Asp

65 70 75 80

Pro Ser His Val Val Leu Ile Asp Cys Leu Thr Leu Trp Val Thr Asn

85 90 95

Leu Met Leu Glu Glu Arg Asp Met Thr Ala Glu Phe Ala Ala Leu Val

100 105 110

Ala Tyr Leu Pro Glu Ala Arg Ala Arg Leu Val Phe Val Ser Asn Glu

115 120 125

Val Gly Leu Gly Ile Val Pro Glu Asn Arg Met Ala Arg Glu Phe Arg

130 135 140

Asp His Ala Gly Arg Leu His Gln Ile Val Ala Glu Lys Ser Ala Glu

145 150 155 160

Val Tyr Phe Val Ala Ala Gly Leu Pro Leu Lys Met Lys Gly

ATGACCACTG CGAGAGCCAA CCAGGGCAAG ATCCCGGCGA CCGTCATCAC CGGCTTCCTC 60

GGCGCCGGCA AGACGACGAT GATCCGCAAC CTGCTGCAGA ACGCCGACGG CAAGCGCATC 120

GGCCTGATCA TCAACGAGTT CGGCGATCTT GGCGTCGACG GCGATGTCTT GAAGGGCTGC 180

GGTGCCGAGG CCTGCACCGA GGACGACATC ATCGAGCTCA CCAATGGCTG CATCTGCTGC 240

ACCGTGGCTG ACGATTTCAT CCCGACCATG ACGAAGCTGC TCGAGCGTGA AAACCGTCCT 300

GACCACATCA TCATCGAAAC CTCGGGCCTT GCCCTGCCGC AGCCGCTGAT CGCCGCTTTC 360

AACTGGCCGG ATATCCGCAG CGAAGTGACC GTCGATGGCG TCGTCACCGT GGTCGACAGC 420

GCCGCCGTTG CCGCTGGCCG CTTTGCCGAC GACCACGACA AGGTCGATGC GCTGCGCGTC 480

GAGGACGACA ATCTCGATCA CGAAAGCCCG ATCGAGGAGC TGTTCGAGGA TCAACTGACG 540

GCTGCCGATC TCATCGTTCT CAACAAGACC GATCTGATCG ATGCCTCCGG CCTCAAGGCC 600

GTGCGCGACG AGGTGTCTTC GCGCACCAGC CGCAAGCCCA CGATGATCGA GGCGAAAAAC 660

GGCGAAGTCG CCGCTGCCAT CCTGCTTGGC CTCGGTGTCG GCACGGAAAG CGATATCGCC 720

AACCGCAAGT CGCATCACGA GATGGAGCAC GAGGCAGGTG AGGAGCACGA TCACGACGAG 780

TTCGACAGCT TCGTCGTCGA GCTCGGTTCG ATCGCCGATC CGGCCGCCTT CATCGATCGC 840

CTGAAGGGCG TAATCGCGGA GCACGACGTT CTGCGCCTCA AGGGTTTTGC AGACGTGCCC 900

GGCAAGCCGA TGCGCCTCCT GATCCAGGCG GTCGGCGCCC GCATCGACCA ATATTACGAC 960

CGCGCCTGGG GCGCTGGCGA AAAGCGCGGT ACGCGCCTCG TCGTCATCGG CCTGCACGAC 1020

ATGGACGAGG CGGCGGTGCG CGCCGCGATC ACCGCGCTCG TGTAG 1065

Met Thr Thr Ala Arg Ala Asn Gln Gly Lys Ile Pro Ala Thr Val Ile

1 5 10 15

Thr Gly Phe Leu Gly Ala Gly Lys Thr Thr Met Ile Arg Asn Leu Leu

20 25 30

Gln Asn Ala Asp Gly Lys Arg Ile Gly Leu Ile Ile Asn Glu Phe Gly

35 40 45

Asp Leu Gly Val Asp Gly Asp Val Leu Lys Gly Cys Gly Ala Glu Ala

50 55 60

Cys Thr Glu Asp Asp Ile Ile Glu Leu Thr Asn Gly Cys Ile Cys Cys

65 70 75 80

Thr Val Ala Asp Asp Phe Ile Pro Thr Met Thr Lys Leu Leu Glu Arg

85 90 95

Glu Asn Arg Pro Asp His Ile Ile Ile Glu Thr Ser Gly Leu Ala Leu

100 105 110

Pro Gln Pro Leu Ile Ala Ala Phe Asn Trp Pro Asp Ile Arg Ser Glu

115 120 125

Val Thr Val Asp Gly Val Val Thr Val Val Asp Ser Ala Ala Val Ala

130 135 140

Ala Gly Arg Phe Ala Asp Asp His Asp Lys Val Asp Ala Leu Arg Val

145 150 155 160

Glu Asp Asp Asn Leu Asp His Glu Ser Pro Ile Glu Glu Leu Phe Glu

165 170 175

Asp Gln Leu Thr Ala Ala Asp Leu Ile Val Leu Asn Lys Thr Asp Leu

180 185 190

Ile Asp Ala Ser Gly Leu Lys Ala Val Arg Asp Glu Val Ser Ser Arg

195 200 205

Thr Ser Arg Lys Pro Thr Met Ile Glu Ala Lys Asn Gly Glu Val Ala

210 215 220

Ala Ala Ile Leu Leu Gly Leu Gly Val Gly Thr Glu Ser Asp Ile Ala

225 230 235 240

Asn Arg Lys Ser His His Glu Met Glu His Glu Ala Gly Glu Glu His

245 250 255

Asp His Asp Glu Phe Asp Ser Phe Val Val Glu Leu Gly Ser Ile Ala

260 265 270

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

275 280 285

Asp Val Leu Arg Leu Lys Gly Phe Ala Asp Val Pro Gly Lys Pro Met

290 295 300

Arg Leu Leu Ile Gln Ala Val Gly Ala Arg Ile Asp Gln Tyr Tyr Asp

305 310 315 320

Arg Ala Trp Gly Ala Gly Glu Lys Arg Gly Thr Arg Leu Val Val Ile

325 330 335

Gly Leu His Asp Met Asp Glu Ala Ala Val Arg Ala Ala Ile Thr Ala

340 345 350

Leu Val

ATGCATCTGC TTCTCGCCCA GAAAGGAACG ATCGCCGACG GCAACGAGGC GATCGACCTT 60

GGGCAAACGC CGGCCGATAT CCTTTTCCTA TCGGCCGCCG ACACCGAGCT CTCCTCGATC 120

GCCGCGGCTC ACGGCCGACG CGACGGAGGC TTGAGCCTGC GCATCGCCAG CCTGATGAGC 180

CTGATGCACC CGATGTCGGT CGACACTTAC GTCGAGCGCA CGGCGCGTCA CGCCAAGCTG 240

ATCGTCGTCC GGCCGCTCGG TGGCGCCAGC TATTTCCGTT ATCTGCTGGA AGCCCTGCAT 300

GCGGCTGCCG TCACCCATCG TTTCGAGATC GCGGTTCTGC CGGGTGACGA CAAGCCGGAT 360

CCGGGGCTGG AGCCTTTCTC CACCGTCGCA GCCGACGACC GCCAGCGCCT TTGGGCTTAC 420

TTCACCGAAG GCGGCTCGGA CAATGCCGGG CTGTTTCTCG ACTATGCGGC CGCACTGGTC 480

ACAGGTGCGG AGAAGCCGCA GCCGGCAAAG CCCCTGTTGA AGGCCGGCAT CTGGTGGCCG 540

GGTGCTGGTG TGATCGGCGT CAGCGAATGG CAGTCCCTTG TTCAGGGACG GATGGTAGCG 600

AGGGAGGGAT TCGAACCCCC GACGGTCGGG ATCTGCTTTT ACCGCGCGCT CGTGCAGAGT 660

GGCGAGACAC GGCCTGTGGA GGCGCTGATC GATGCGCTGG AGGCTGAAGG TGTGCGGGCA 720

CTGCCGGTGT TTGTCTCAAG CCTCAAGGAT GCCGTTTCCG TCGGCACGCT GCAGGCGATT 780

TTTTCCGAGG CCGCACCCGA CGTGGTGATG AACGCCACTG GCTTTGCGGT CTCGTCGCCC 840

GGTGCCGACC GTCAGCCGAC GGTGCTGGAA TCGACCGGTG CGCCGGTGCT GCAGGTGATT 900

TTCTCCGGCT CGTCGCGGGC GCAATGGGAA ACGTCGCCGC AGGGGCTGAT GGCGCGCGAC 960

CTCGCCATGA ACGTGGCACT CCCCGAAGTC GATGGCCGCA TCCTTGCGCG CGCCGTCTCC 1020

TTCAAGGCGG CGTCGATCTA TGACGCCAAG GTGGAGGCCA ATATCGTCGG CCATGAGCCG 1080

CTCGAAGGCC GGGTGCGCTT TGCCGCTGAT CTTGCCGTCA ACTGGGCGAA CGTGCGCCGG 1140

GCAGAGCCCG CCGAGCGCCG TATTGCCATC GTCATGGCCA ACTATCCGAA CCGCGACGGT 1200

CGCCTCGGCA ACGGTGTCGG GCTCGACACG CCGGCCGGTA CCGTCGAGGT GCTTAGCGCC 1260

ATGGCGCGGG AAGGCTATGC GGTCGGTGAG GTTCCCGCCG ATGGCGACGC GCTGATCCGC 1320

TTTCTGATGG CCGGGCCGAC CAATGCGGCG AGCCATGACC GTGAAATCCG CGAGCGTATT 1380

TCGCTGAACG ATTACAAAAC GTTCTTCGAT TCGCTTCCGA AACAGATAAA GGATGAAGTT 1440

GCCGGTCGCT GGGGCGTGCC GGAGGCCGAT CCCTTTTTCC TCGATGGCGC CTTCGCGCTG 1500

CCGCTCGCCC GCTTCGGCGA GGTGATCGTC GGCATCCAAC CGGCGCGCGG CTACAACATC 1560

GATCCGAAGG AAAGCTACCA TTCCCCGGAC CTCGTGCCGC CGCATGGCTA TCTCGCCTTC 1620

TACGCCTTCC TGCGCCAGCA GTTCGGAGCG CAGGCGATCG TCCACATGGG CAAGCACGGC 1680

AATCTCGAAT GGCTGCCGGG CAAGGCGCTG GCGCTGTCGG AAACCTGCTA TCCCGAAGCG 1740

ATCTTCGGGC CGCTGCCGCA CATCTATCCC TTCATCGTCA ACGATCCGGG CGAAGGTACG 1800

CAGGCCAAGC GCCGCACCAG CGCCGTCATC ATCGACCACC TGACCCCGCC CTTGACGCGC 1860

GCCGAATCCT ACGGCCCGCT CAAGGATCTG GAAGCGCTCG TCGACGAATA TTACGACGCC 1920

GCCGGCGGTG ATCCGCGCCG CCTCAGGCTG CTCAGCCGCC AGATCCTCGA TCTCGTGCGC 1980

GACATCGGCC TCGACAGCGA CGCAGGCATC GACAGGGGCG ACAGCGACGA CAAGGCGCTG 2040

GAAAAGCTCG ACGCCTATCT CTGCGACCTC AAGGAAATGC AGATCCGCGA CGGCCTGCAC 2100

ATCTTCGGCG TTGCGCCGGA AGGGCGGTTG TTGACGGACC TCACCGTAGC GCTGGCGCGC 2160

GTGCCCCGAG GTCTCGGCGA GGGCGGCGAC CAGAGCCTGC AGCGGGCGAT CGCAGCGGAT 2220

GCGGGGCTGC GTGGGTTTGC TATTCCCACC TCGGCGGGGG GCAACCCCGC ACGCGACGCC 2280

CAACCCTTCG ACCCGCTCGA CTGCGTCATG TCCGACACCT GGACAGGCCC GAAACCGTCC 2340

ATCCTCGCTG ACCTCTCGGA CGCCCCCTGG CGCACCGCCG GCGATACGGT CGAGCGCATC 2400

GAGTTGCTTG CCGCAAATCT CGTGTCGGGT GAACTGGCTT GCCCGGACCA CTGGGCCAAC 2460

ACCCGCGCCG TGCTCGGCGA AATCGAAACG CGCCTGAAGC CGTCGATTTC AAACTCGGGT 2520

GCCGCCGAGA TGACCGGCTT CCTCACCGGT CTCAGCGGCC GCTTCGTCGC CCCCGGTCCA 2580

TCGGGCGCGC CGACGCGCGG CCGGCCGGAT GTGTTGCCGA CGGGGCGCAA TTTCTACTCG 2640

GTCGACAGCC GCGCCGTGCC GACGCCGGCG GCTTACGAGC TTGGCAAGAA ATCGGCCGAG 2700

CTTCTGATCC GCCGCTACCT GCAGGACCAT GGCGAATGGC CGTCCTCCTT TGGCCTGACC 2760

GCCTGGGGCA CGGCGAACAT GCGCACCGGC GGCGACGACA TCGCCCAGGC CCTGGCGCTG 2820

ATCGGCGCCA AGCCCACCTG GGACATGGTC TCTCGCCGGG TGATGGGCTA CGAGATCGTG 2880

CCGCTCGCAG TCCTCGGCCG CCCACGCGTC GACGTGACCT TGCGCATTTC CGGCTTCTTC 2940

CGCGATGCCT TCCCGGACCA GATCGCGCTC TTCGACAAGG CGATCCGCGC CGTCGCGCTG 3000

GAGGAAGACG ATGCCGACAA CATGATCGCC GCACGCATGC GGGCGGAAAG CCGGCGGCTG 3060

GAGGCCGAAG GCGTGGAAGC CGCCGAGGCC GCGCGTCGCG CCTCCTACCG CGTCTTTGGC 3120

GCAAAGCCCG GTGCCTATGG CGCCGCCCTG CAGGCGCTGA TCGACGAGAA GGGCTGGGAA 3180

ACCAAAGCAG ATCTCGCCGA GGCCTATCTT ACCTGGGGCG CCTATGCCTA TGGCGCCGGC 3240

GAGGAGGGCA AGGCCGAGCG CGATCTTTTC GAGGAGCGCC TGCGCACGAT AGAGGCGGTG 3300

GTGCAGAACC AGGACAACCG CGAGCACGAT CTGCTCGACA GCGACGACTA CTACCAGTTC 3360

GAAGGCGGCA TGAGCGCTGC CGCCGAACAG CTCGGCGGTC ACCGTCCGGC GATCTACCAC 3420

AACGACCATT CCCGTCCGGA AAAGCCTGTG ATCCGGTCGC TCGAAGAAGA GATCGGCCGC 3480

GTGGTCCGGG CCCGCGTCGT CAATCCCAAG TGGATCGATG GCGTCATGCG CCACGGATAC 3540

AAGGGCGCCT TCGAGATCGC TGCCACGGTC GACTACATGT TCGCCTTTGC CGCGACCACG 3600

GGTGCGGTGC GCGACCATCA TTTCGAGGCC GCTTATCAGG CGTTCATTGT CGACGAGCGC 3660

GTGGCTGACT TCATGCGCGA CAAGAACCCG GCCGCCTTTG CCGAGCTTGC CGAACGCCTG 3720

CTTGAAGCAA TCGACCGCAA TCTCTGGACG CCGCGCTCGA ATTCGGCGCG GTTTGAACTT 3780

GCCGGCATCG GCACGGCAGC AACCCGGCTT CGTGCCGGCA ATGAATAG 3828

Met His Leu Leu Leu Ala Gln Lys Gly Thr Ile Ala Asp Gly Asn Glu

1 5 10 15

Ala Ile Asp Leu Gly Gln Thr Pro Ala Asp Ile Leu Phe Leu Ser Ala

20 25 30

Ala Asp Thr Glu Leu Ser Ser Ile Ala Ala Ala His Gly Arg Arg Asp

35 40 45

Gly Gly Leu Ser Leu Arg Ile Ala Ser Leu Met Ser Leu Met His Pro

50 55 60

Met Ser Val Asp Thr Tyr Val Glu Arg Thr Ala Arg His Ala Lys Leu

65 70 75 80

Ile Val Val Arg Pro Leu Gly Gly Ala Ser Tyr Phe Arg Tyr Leu Leu

85 90 95

Glu Ala Leu His Ala Ala Ala Val Thr His Arg Phe Glu Ile Ala Val

100 105 110

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

115 120 125

Val Ala Ala Asp Asp Arg Gln Arg Leu Trp Ala Tyr Phe Thr Glu Gly

130 135 140

Gly Ser Asp Asn Ala Gly Leu Phe Leu Asp Tyr Ala Ala Ala Leu Val

145 150 155 160

Thr Gly Ala Glu Lys Pro Gln Pro Ala Lys Pro Leu Leu Lys Ala Gly

165 170 175

Ile Trp Trp Pro Gly Ala Gly Val Ile Gly Val Ser Glu Trp Gln Ser

180 185 190

Leu Val Gln Gly Arg Met Val Ala Arg Glu Gly Phe Glu Pro Pro Thr

195 200 205

Val Gly Ile Cys Phe Tyr Arg Ala Leu Val Gln Ser Gly Glu Thr Arg

210 215 220

Pro Val Glu Ala Leu Ile Asp Ala Leu Glu Ala Glu Gly Val Arg Ala

225 230 235 240

Leu Pro Val Phe Val Ser Ser Leu Lys Asp Ala Val Ser Val Gly Thr

245 250 255

Leu Gln Ala Ile Phe Ser Glu Ala Ala Pro Asp Val Val Met Asn Ala

260 265 270

Thr Gly Phe Ala Val Ser Ser Pro Gly Ala Asp Arg Gln Pro Thr Val

275 280 285

Leu Glu Ser Thr Gly Ala Pro Val Leu Gln Val Ile Phe Ser Gly Ser

290 295 300

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

305 310 315 320

Leu Ala Met Asn Val Ala Leu Pro Glu Val Asp Gly Arg Ile Leu Ala

325 330 335

Arg Ala Val Ser Phe Lys Ala Ala Ser Ile Tyr Asp Ala Lys Val Glu

340 345 350

Ala Asn Ile Val Gly His Glu Pro Leu Glu Gly Arg Val Arg Phe Ala

355 360 365

Ala Asp Leu Ala Val Asn Trp Ala Asn Val Arg Arg Ala Glu Pro Ala

370 375 380

Glu Arg Arg Ile Ala Ile Val Met Ala Asn Tyr Pro Asn Arg Asp Gly

385 390 395 400

Arg Leu Gly Asn Gly Val Gly Leu Asp Thr Pro Ala Gly Thr Val Glu

405 410 415

Val Leu Ser Ala Met Ala Arg Glu Gly Tyr Ala Val Gly Glu Val Pro

420 425 430

Ala Asp Gly Asp Ala Leu Ile Arg Phe Leu Met Ala Gly Pro Thr Asn

435 440 445

Ala Ala Ser His Asp Arg Glu Ile Arg Glu Arg Ile Ser Leu Asn Asp

450 455 460

Tyr Lys Thr Phe Phe Asp Ser Leu Pro Lys Gln Ile Lys Asp Glu Val

465 470 475 480

Ala Gly Arg Trp Gly Val Pro Glu Ala Asp Pro Phe Phe Leu Asp Gly

485 490 495

Ala Phe Ala Leu Pro Leu Ala Arg Phe Gly Glu Val Ile Val Gly Ile

500 505 510

Gln Pro Ala Arg Gly Tyr Asn Ile Asp Pro Lys Glu Ser Tyr His Ser

515 520 525

Pro Asp Leu Val Pro Pro His Gly Tyr Leu Ala Phe Tyr Ala Phe Leu

530 535 540

Arg Gln Gln Phe Gly Ala Gln Ala Ile Val His Met Gly Lys His Gly

545 550 555 560

Asn Leu Glu Trp Leu Pro Gly Lys Ala Leu Ala Leu Ser Glu Thr Cys

565 570 575

Tyr Pro Glu Ala Ile Phe Gly Pro Leu Pro His Ile Tyr Pro Phe Ile

580 585 590

Val Asn Asp Pro Gly Glu Gly Thr Gln Ala Lys Arg Arg Thr Ser Ala

595 600 605

Val Ile Ile Asp His Leu Thr Pro Pro Leu Thr Arg Ala Glu Ser Tyr

610 615 620

Gly Pro Leu Lys Asp Leu Glu Ala Leu Val Asp Glu Tyr Tyr Asp Ala

625 630 635 640

Ala Gly Gly Asp Pro Arg Arg Leu Arg Leu Leu Ser Arg Gln Ile Leu

645 650 655

Asp Leu Val Arg Asp Ile Gly Leu Asp Ser Asp Ala Gly Ile Asp Arg

660 665 670

Gly Asp Ser Asp Asp Lys Ala Leu Glu Lys Leu Asp Ala Tyr Leu Cys

675 680 685

Asp Leu Lys Glu Met Gln Ile Arg Asp Gly Leu His Ile Phe Gly Val

690 695 700

Ala Pro Glu Gly Arg Leu Leu Thr Asp Leu Thr Val Ala Leu Ala Arg

705 710 715 720

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

725 730 735

Ile Ala Ala Asp Ala Gly Leu Arg Gly Phe Ala Ile Pro Thr Ser Ala

740 745 750

Gly Gly Asn Pro Ala Arg Asp Ala Gln Pro Phe Asp Pro Leu Asp Cys

755 760 765

Val Met Ser Asp Thr Trp Thr Gly Pro Lys Pro Ser Ile Leu Ala Asp

770 775 780

Leu Ser Asp Ala Pro Trp Arg Thr Ala Gly Asp Thr Val Glu Arg Ile

785 790 795 800

Glu Leu Leu Ala Ala Asn Leu Val Ser Gly Glu Leu Ala Cys Pro Asp

805 810 815

His Trp Ala Asn Thr Arg Ala Val Leu Gly Glu Ile Glu Thr Arg Leu

820 825 830

Lys Pro Ser Ile Ser Asn Ser Gly Ala Ala Glu Met Thr Gly Phe Leu

835 840 845

Thr Gly Leu Ser Gly Arg Phe Val Ala Pro Gly Pro Ser Gly Ala Pro

850 855 860

Thr Arg Gly Arg Pro Asp Val Leu Pro Thr Gly Arg Asn Phe Tyr Ser

865 870 875 880

Val Asp Ser Arg Ala Val Pro Thr Pro Ala Ala Tyr Glu Leu Gly Lys

885 890 895

Lys Ser Ala Glu Leu Leu Ile Arg Arg Tyr Leu Gln Asp His Gly Glu

900 905 910

Trp Pro Ser Ser Phe Gly Leu Thr Ala Trp Gly Thr Ala Asn Met Arg

915 920 925

Thr Gly Gly Asp Asp Ile Ala Gln Ala Leu Ala Leu Ile Gly Ala Lys

930 935 940

Pro Thr Trp Asp Met Val Ser Arg Arg Val Met Gly Tyr Glu Ile Val

945 950 955 960

Pro Leu Ala Val Leu Gly Arg Pro Arg Val Asp Val Thr Leu Arg Ile

965 970 975

Ser Gly Phe Phe Arg Asp Ala Phe Pro Asp Gln Ile Ala Leu Phe Asp

980 985 990

Lys Ala Ile Arg Ala Val Ala Leu Glu Glu Asp Asp Ala Asp Asn Met

995 1000 1005

Ile Ala Ala Arg Met Arg Ala Glu Ser Arg Arg Leu Glu Ala Glu Gly

1010 1015 1020

Val Glu Ala Ala Glu Ala Ala Arg Arg Ala Ser Tyr Arg Val Phe Gly

1025 1030 1035 1040

Ala Lys Pro Gly Ala Tyr Gly Ala Ala Leu Gln Ala Leu Ile Asp Glu

1045 1050 1055

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

1060 1065 1070

Gly Ala Tyr Ala Tyr Gly Ala Gly Glu Glu Gly Lys Ala Glu Arg Asp

1075 1080 1085

Leu Phe Glu Glu Arg Leu Arg Thr Ile Glu Ala Val Val Gln Asn Gln

1090 1095 1100

Asp Asn Arg Glu His Asp Leu Leu Asp Ser Asp Asp Tyr Tyr Gln Phe

1105 1110 1115 1120

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

1125 1130 1135

Ala Ile Tyr His Asn Asp His Ser Arg Pro Glu Lys Pro Val Ile Arg

1140 1145 1150

Ser Leu Glu Glu Glu Ile Gly Arg Val Val Arg Ala Arg Val Val Asn

1155 1160 1165

Pro Lys Trp Ile Asp Gly Val Met Arg His Gly Tyr Lys Gly Ala Phe

1170 1175 1180

Glu Ile Ala Ala Thr Val Asp Tyr Met Phe Ala Phe Ala Ala Thr Thr

1185 1190 1195 1200

Gly Ala Val Arg Asp His His Phe Glu Ala Ala Tyr Gln Ala Phe Ile

1205 1210 1215

Val Asp Glu Arg Val Ala Asp Phe Met Arg Asp Lys Asn Pro Ala Ala

1220 1225 1230

Phe Ala Glu Leu Ala Glu Arg Leu Leu Glu Ala Ile Asp Arg Asn Leu

1235 1240 1245

Trp Thr Pro Arg Ser Asn Ser Ala Arg Phe Glu Leu Ala Gly Ile Gly

1250 1255 1260

Thr Ala Ala Thr Arg Leu Arg Ala Gly Asn Glu

1265 1270 1275

ATGAGCGACG AGACGACAGT AGGCGGCGAA GCCCCGGCCG AGAAGGACGA TGCCCGCCAC 60

GCCATGAAGA TGGCGAAGAA GAAGGCAGCA CGCGAAAAGA TCATGGCGAC GAAGACCGAC 120

GAGAAGGGTC TGATCATCGT CAACACCGGC AAAGGCAAGG GCAAGTCGAC CGCCGGCTTC 180

GGCATGATCT TCCGCCATAT CGCCCACGGC ATGCCCTGCG CCGTCGTGCA GTTCATCAAG 240

GGTGCGATGG CAACCGGCGA GCGCGAGTTG ATCGAGAAGC ATTTCGGCGA TGTCTGCCAG 300

TTCTACACGC TCGGCGAGGG CTTCACCTGG GAAACGCAGG ATCGCGCCCG CGATGTTGCG 360

ATGGCTGAAA AGGCCTGGGA GAAGGCGAAG GAACTGATCC GTGACGAGCG CAACTCGATG 420

GTGCTGCTCG ACGAGATCAA CATTGCTCTG CGCTACGACT ACATCGACGT CGCCGAAGTG 480

GTGCGCTTCC TGAAGGAAGA AAAGCCGCAC ATGACGCATG TGGTGCTCAC CGGCCGCAAC 540

GCGAAAGAAG ACCTGATCGA AGTCGCCGAT CTCGTCACTG AGATGGAGCT GATCAAGCAT 600

CCGTTCCGTT CCGGCATCAA GGCGCAGCAG GGCGTGGAGT TCTGA 645

Met Ser Asp Glu Thr Thr Val Gly Gly Glu Ala Pro Ala Glu Lys Asp

1 5 10 15

Asp Ala Arg His Ala Met Lys Met Ala Lys Lys Lys Ala Ala Arg Glu

20 25 30

Lys Ile Met Ala Thr Lys Thr Asp Glu Lys Gly Leu Ile Ile Val Asn

35 40 45

Thr Gly Lys Gly Lys Gly Lys Ser Thr Ala Gly Phe Gly Met Ile Phe

50 55 60

Arg His Ile Ala His Gly Met Pro Cys Ala Val Val Gln Phe Ile Lys

65 70 75 80

Gly Ala Met Ala Thr Gly Glu Arg Glu Leu Ile Glu Lys His Phe Gly

85 90 95

Asp Val Cys Gln Phe Tyr Thr Leu Gly Glu Gly Phe Thr Trp Glu Thr

100 105 110

Gln Asp Arg Ala Arg Asp Val Ala Met Ala Glu Lys Ala Trp Glu Lys

115 120 125

Ala Lys Glu Leu Ile Arg Asp Glu Arg Asn Ser Met Val Leu Leu Asp

130 135 140

Glu Ile Asn Ile Ala Leu Arg Tyr Asp Tyr Ile Asp Val Ala Glu Val

145 150 155 160

Val Arg Phe Leu Lys Glu Glu Lys Pro His Met Thr His Val Val Leu

165 170 175

Thr Gly Arg Asn Ala Lys Glu Asp Leu Ile Glu Val Ala Asp Leu Val

180 185 190

Thr Glu Met Glu Leu Ile Lys His Pro Phe Arg Ser Gly Ile Lys Ala

195 200 205

Gln Gln Gly Val Glu Phe

210

CCATAATTCT TTTATAATTT AAACGGTGAA CACATGGTAG TTTATTTAGT AGGTGCGGGT 60

CCAGGAGATC CCGAACTTAT CACTCTCAAA GCTGTAAACG TGTTAAAAAA AGCGGATGTT 120

GTACTGTACG ACAAACCTGC AAATGAAGAA ATTTTAAAGT ATGCTGAAGG TGCAAAACTA 180

ATATATGTCG GAAAACAAGC AGGACATCAT TACAAATCTC AAAATGAAAT CAATACTCTT 240

CTTGTTGAAG AAGCAAAAGA AAATGATTTA GTAGTACGCC TTAAAGGTGG AGACCCCTTT 300

GTATTTGGAA GAGGAGGCGA GGAAATTCTG GCCCTTGTAG AAGAAGGAAT TGATTTTGAG 360

TTAGTTCCAG GGGTAACTTC TGCAATTGGA GTTCCAACAA CAATTGGGCT TCCAGTTACT 420

CATAGAGGTG TTGCAACATC GTTTACAGTT GTTACAGGTC ATGAAGACCC AACAAAATGC 480

AAGAAACAGG TAGGATGGGA CTTTAAAGCA GATACTATTG TAATACTTAT GGGTATTGGA 540

AATTTAGCTG AAAATACAGC AGAAATTATG AAACATAAAG ATCCTGAAAC TCCAGTTTGT 600

GTAATTGAAA ATGGTACGAT GGAAGGTCAA AGGATAATAA CGGGCACACT GGAAAATATA 660

GCTGGAAAGG ATATTAAACC TCCTGCTTTA GTGGTATTGG AAATGTTGTC AATGTTTTTA 720

AAGAAATGAA TCAAATCAGT GGCTGATCTA TTAAGAAGGC AATATCATGA ATGGATTAGA 780

AGGTAAAAAA ATTGTTATAA CAAGACCTGC TGAAAGGGCT AAAGACTCAG TTGAAATGGT 840

AAAATCTTAT GGAGCAGTTC CAATTGTAAC TCCTACAATT GAACTCAAAG ATTCCAAGCC 900

AGAAGAAGTG ATAAAATTAT GTAATATGAT AAATGAACCT TGATTGGCCT TATAT 955

ATGGTAGTTT ATTTAGTAGG TGCGGGTCCA GGAGATCCCG AACTTATCAC TCTCAAAGCT 60

GTAAACGTGT TAAAAAAAGC GGATGTTGTA CTGTACGACA AACCTGCAAA TGAAGAAATT 120

TTAAAGTATG CTGAAGGTGC AAAACTAATA TATGTCGGAA AACAAGCAGG ACATCATTAC 180

AAATCTCAAA ATGAAATCAA TACTCTTCTT GTTGAAGAAG CAAAAGAAAA TGATTTAGTA 240

GTACGCCTTA AAGGTGGAGA CCCCTTTGTA TTTGGAAGAG GAGGCGAGGA AATTCTGGCC 300

CTTGTAGAAG AAGGAATTGA TTTTGAGTTA GTTCCAGGGG TAACTTCTGC AATTGGAGTT 360

CCAACAACAA TTGGGCTTCC AGTTACTCAT AGAGGTGTTG CAACATCGTT TACAGTTGTT 420

ACAGGTCATG AAGACCCAAC AAAATGCAAG AAACAGGTAG GATGGGACTT TAAAGCAGAT 480

ACTATTGTAA TACTTATGGG TATTGGAAAT TTAGCTGAAA ATACAGCAGA AATTATGAAA 540

CATAAAGATC CTGAAACTCC AGTTTGTGTA ATTGAAAATG GTACGATGGA AGGTCAAAGG 600

ATAATAACGG GCACACTGGA AAATATAGCT GGAAAGGATA TTAAACCTCC TGCTTTAGTG 660

GTATTGGAAA TGTTGTCAAT GTTTTTAAAG AAATGA 696

Met Val Val Tyr Leu Val Gly Ala Gly Pro Gly Asp Pro Glu Leu Ile

1 5 10 15

Thr Leu Lys Ala Val Asn Val Leu Lys Lys Ala Asp Val Val Leu Tyr

20 25 30

Asp Lys Pro Ala Asn Glu Glu Ile Leu Lys Tyr Ala Glu Gly Ala Lys

35 40 45

Leu Ile Tyr Val Gly Lys Gln Ala Gly His His Tyr Lys Ser Gln Asn

50 55 60

Glu Ile Asn Thr Leu Leu Val Glu Glu Ala Lys Glu Asn Asp Leu Val

65 70 75 80

Val Arg Leu Lys Gly Gly Asp Pro Phe Val Phe Gly Arg Gly Gly Glu

85 90 95

Glu Ile Leu Ala Leu Val Glu Glu Gly Ile Asp Phe Glu Leu Val Pro

100 105 110

Gly Val Thr Ser Ala Ile Gly Val Pro Thr Thr Ile Gly Leu Pro Val

115 120 125

Thr His Arg Gly Val Ala Thr Ser Phe Thr Val Val Thr Gly His Glu

130 135 140

Asp Pro Thr Lys Cys Lys Lys Gln Val Gly Trp Asp Phe Lys Ala Asp

145 150 155 160

Thr Ile Val Ile Leu Met Gly Ile Gly Asn Leu Ala Glu Asn Thr Ala

165 170 175

Glu Ile Met Lys His Lys Asp Pro Glu Thr Pro Val Cys Val Ile Glu

180 185 190

Asn Gly Thr Met Glu Gly Gln Arg Ile Ile Thr Gly Thr Leu Glu Asn

195 200 205

Ile Ala Gly Lys Asp Ile Lys Pro Pro Ala Leu Val Val Leu Glu Met

210 215 220

Leu Ser Met Phe Leu Lys Lys

225 230

Glu Gln Leu Ile Asn Glu Pro Leu Asp His Arg Gly Glu Val Val Leu

5 10 15

Val Gly Ala Gly Pro Gly Asp Ala Gly Leu Leu Thr Leu Lys Gly Leu

20 25 30

Gln Gln Ile Gln Gln Ala Asp Val Val Val Tyr Asp Arg Leu Val Ser

35 40 45

Asp Asp Ile Met Asn Leu Val Arg Arg Asp Ala Asp Arg Val Phe Val

50 55 60

Gly Lys Arg Ala Gly Tyr His Cys Val Pro Gln Glu Glu Ile Asn Gln

65 70 75 80

Ile Leu Leu Arg Glu Ala Gln Lys Gly Lys Arg Val Val Arg Leu Lys

85 90 95

Gly Gly Asp Pro Phe Ile Phe Gly Arg Gly Gly Glu Glu Leu Glu Thr

100 105 110

Leu Cys Asn Ala Gly Ile Pro Phe Ser Val Val Pro Gly Ile Thr Ala

115 120 125

Ala Ser Gly Cys Ser Ala Tyr Ser Gly Ile Pro Leu Thr His Arg Asp

130 135 140

Tyr Ala Gln Ser Val Arg Leu Ile Thr Gly His Leu Lys Thr Gly Gly

145 150 155 160

Glu Leu Asp Trp Glu Asn Leu Ala Ala Glu Lys Gln Thr Leu Val Phe

165 170 175

Tyr Met Gly Leu Asn Gln Ala Ala Thr Ile Gln Gln Lys Leu Ile Glu

180 185 190

His Gly Met Pro Gly Glu Met Pro Val Ala Ile Val Glu Asn Gly Thr

195 200 205

Ala Val Thr Gln Arg Val Ile Asp Gly Thr Leu Thr Gln Leu Gly Glu

210 215 220

Leu Ala Gln Gln Met Asn Ser Pro Ser Leu Ile Ile Ile Gly Arg Val

225 230 235 240

Val Gly Leu Arg Asp Lys Leu Asn Trp Phe Ser

245 250

27

Nucleic Acid

Single

Unknown

Oligonucleotide

No

fragment of sumT gene

56

CGCGGAATTC CCNGGNGAYC CNGARCT 27

27

Nucleic Acid

single

Unknown

Oligonucleotide

No

fragment of sumT gene

57

CGCGGAATTC GTRTAYCTWG TDGGWGC 27

25

Nucleic Acid

single

Unknown

Oligonucleotide

No

fragment of sumT gene

58

CGCGAAGCTT RTTYTCWAGD GTNCC 25

GGCCGAATTC ATATGGTAGT TTATTTA 27

GGCCGAGCTC TATTACATAA TT 22