Patent Application: US-45355295-A

Abstract:
mammalian expression systems for the production of hcv proteins . such expression systems provide high yields of hcv proteins , and enable the development of diagnostic and therapeutic reagents which contain glycosylated structural antigens and also allow for the isolation of the hcv etiological agent .

Description:
the present invention provides full - length genomic clones useful in a variety of aspects . such full - length genomic clones can allow culture of the hcv virus which in turn is useful for a variety of purposes . successful culture of the hcv virus can allow for the development of viral replication inhibitors , viral proteins for diagnostic applications , viral proteins for therapeutics , and specifically structural viral antigens , including , for example , hcv putative envelope , hcv putative e1 and hcv putative e2 fragments . cell lines which can be used for viral replication are numerous , and include ( but are not limited to ), for example , primary hepatocytes , permanent or semi - permanent hepatocytes , cultures transfected with transforming viruses or transforming genes . especially useful cell lines could include , for example , permanent hepatocyte cultures that continuously express any of several heterologous rna polymerase genes to amplify hcv rna sequences under the control of these specific rna polymerase sequences . sources of hcv viral sequences encoding structural antigens include putative core , putative e1 and putative e2 fragments . expression can be performed in both prokaryotic and eukaryotic systems . the expression of hcv proteins in mammalian expression systems allows for glycosylated proteins such as the e1 and e2 proteins , to be produced . these glycosylated proteins have diagnostic utility in a variety of aspects , including , for example , assay systems for screening and prognostic applications . the mammalian expression of hcv viral proteins allows for inhibitor studies including elucidation of specific viral attachment sites or sequences and / or viral receptors on susceptible cell types , for example , liver cells and the like . the procurement of specific expression clones developed as described herein in mammalian expression systems provides antigens for diagnostic assays which can determine the stage of hcv infection , such as , for example , acute versus on - going or persistent infections , and / or recent infection versus past exposure . these specific expression clones also provide prognostic markers for resolution of disease such as to distinguish resolution of disease from chronic hepatitis caused by hcv . it is contemplated that earlier seroconversion to glycosylated structural antigens possibly may be detected by using proteins produced in these mammalian expression systems . antibodies , both monoclonal and polyclonal , also may be produced from the proteins derived from these mammalian expression systems which then in turn may be used for diagnostic , prognostic and therapeutic applications . also , reagents produced from these novel expression systems described herein may be useful in the characterization and or isolation of other infectious agents . proteins produced from these mammalian expression systems , as well as reagents produced from these proteins , can be placed into appropriate container and packaged as test kits for convenience in performing assays . other aspects of the present invention include a polypeptide comprising an hcv epitope attached to a solid phase and an antibody to an hcv epitope attached to a solid phase . also included are methods for producing a polypeptide containing an hcv epitope comprising incubating host cells transformed with a mammalian expression vector containing a sequence encoding a polypeptide containing an hcv epitope under conditions which allow expression of the polypeptide , and a polypeptide containing an hcv epitope produced by this method . the present invention provides assays which utilize the recombinant or synthetic polypeptides provided by the invention , as well as the antibodies described herein in various formats , any of which may employ a signal generating compound in the assay . assays which do not utilize signal generating compounds to provide a means of detection also are provided . all of the assays described generally detect either antigen or antibody , or both , and include contacting a test sample with at least one reagent provided herein to form at least one antigen / antibody complex and detecting the presence of the complex . these assays are described in detail herein . vaccines for treatment of hcv infection comprising an immunogenic peptide obtained from a mammalian expression system containing an hcv epitope , or an inactivated preparation of hcv , or an attenuated preparation of hcv also are included in the present invention . also included in the present invention is a method for producing antibodies to hcv comprising administering to an individual an isolated immunogenic polypeptide containing an hcv epitope in an amount sufficient to produce an immune response in the inoculated individual . also provided by the present invention is a tissue culture grown cell infected with hcv . the term &# 34 ; antibody containing body component &# 34 ; ( or test sample ) refers to a component of an individual &# 39 ; s body which is the source of the antibodies of interest . these components are well known in the art . these samples include biological samples which can be tested by the methods of the present invention described herein and include human and animal body fluids such as whole blood , serum , plasma , cerebrospinal fluid , urine , lymph fluids , and various external sections of the respiratory , intestinal and genitourinary tracts , tears , saliva , milk , white blood cells , myelomas and the like , biological fluids such as cell culture supernatants , fixed tissue specimens and fixed cell specimens . after preparing recombinant proteins , as described by the present invention , the recombinant proteins can be used to develop unique assays as described herein to detect either the presence of antigen or antibody to hcv . these compositions also can be used to develop monoclonal and / or polyclonal antibodies with a specific recombinant protein which specifically binds to the immunological epitope of hcv which is desired by the routineer . also , it is contemplated that at least one recombinant protein of the invention can be used to develop vaccines by following methods known in the art . it is contemplated that the reagent employed for the assay can be provided in the form of a kit with one or more containers such as vials or bottles , with each container containing a separate reagent such as a monoclonal antibody , or a cocktail of monoclonal antibodies , or a polypeptide ( either recombinant or synthetic ) employed in the assay . &# 34 ; solid phases &# 34 ; (&# 34 ; solid supports &# 34 ;) are known to those in the art and include the walls of wells of a reaction tray , test tubes , polystyrene beads , magnetic beads , nitrocellulose strips , membranes , microparticles such as latex particles , and others . the &# 34 ; solid phase &# 34 ; is not critical and can be selected by one skilled in the art . thus , latex particles , microparticles , magnetic or non - magnetic beads , membranes , plastic tubes , walls of microtiter wells , glass or silicon chips and sheep red blood cells are all suitable examples . suitable methods for immobilizing peptides on solid phases include ionic , hydrophobic , covalent interactions and the like . a &# 34 ; solid phase &# 34 ;, as used herein , refers to any material which is insoluble , or can be made insoluble by a subsequent reaction . the solid phase can be chosen for its intrinsic ability to attract and immobilize the capture reagent . alternatively , the solid phase can retain an additional receptor which has the ability to attract and immobilize the capture reagent . the additional receptor can include a charged substance that is oppositely charged with respect to the capture reagent itself or to a charged substance conjugated to the capture reagent . as yet another alternative , the receptor molecule can be any specific binding member which is immobilized upon ( attached to ) the solid phase and which has the ability to immobilize the capture reagent through a specific binding reaction . the receptor molecule enables the indirect binding of the capture reagent to a solid phase material before the performance of the assay or during the performance of the assay . the solid phase thus can be a plastic , derivatized plastic , magnetic or non - magnetic metal , glass or silicon surface of a test tube , microliter well , sheet , bead , microparticle , chip , and other configurations known to those of ordinary skill in the art . it is contemplated and within the scope of the invention that the solid phase also can comprise any suitable porous material with sufficient porosity to allow access by detection antibodies and a suitable surface affinity to bind antigens . microporous structures are generally preferred , but materials with gel structure in the hydrated state may be used as well . such useful solid supports include : natural polymeric carbohydrates and their synthetically modified , cross - linked or substituted derivatives , such as agar , agarose , cross - linked alginic acid , substituted and cross - linked guar gums , cellulose esters , especially with nitric acid and carboxylic acids , mixed cellulose esters , and cellulose ethers ; natural polymers containing nitrogen , such as proteins and derivatives , including cross - linked or modified gelatins ; natural hydrocarbon polymers , such as latex and rubber ; synthetic polymers which may be prepared with suitably porous structures , such as vinyl polymers , including polyethylene , polypropylene , polystyrene , polyvinylchloride , polyvinylacetate and its partially hydrolyzed derivatives , polyacrylamides , polymethacrylates , copolymers and terpolymers of the above polycondensates , such as polyesters , polyamides , and other polymers , such as polyurethanes or polyepoxides ; porous inorganic materials such as sulfates or carbonates of alkaline earth metals and magnesium , including barium sulfate , calcium sulfate , calcium carbonate , silicates of alkali and alkaline earth metals , aluminum and magnesium ; and aluminum or silicon oxides or hydrates , such as clays , alumina , talc , kaolin , zeolite , silica gel , or glass ( these materials may be used as filters with the above polymeric materials ); and mixtures or copolymers of the above classes , such as graft copolymers obtained by initializing polymerization of synthetic polymers on a pre - existing natural polymer . all of these materials may be used in suitable shapes , such as films , sheets , or plates , or they may be coated onto or bonded or laminated to appropriate inert carriers , such as paper , glass , plastic films , or fabrics . the porous structure of nitrocellulose has excellent absorption and adsorption qualities for a wide variety of reagents including monoclonal antibodies . nylon also possesses similar characteristics and also is suitable . it is contemplated that such porous solid supports described hereinabove are preferably in the form of sheets of thickness from about 0 . 01 to 0 . 5 mm , preferably about 0 . 1 mm . the pore size may vary within wide limits , and is preferably from about 0 . 025 to 15 microns , especially from about 0 . 15 to 15 microns . the surfaces of such supports may be activated by chemical processes which cause covalent linkage of the antigen or antibody to the support . the irreversible binding of the antigen or antibody is obtained , however , in general , by adsorption on the porous material by poorly understood hydrophobic forces . suitable solid supports also are described in u . s . patent application ser . no . 227 , 272 . the &# 34 ; indicator reagent &# 34 ; comprises a &# 34 ; signal generating compound &# 34 ; ( label ) which is capable of generating a measurable signal detectable by external means conjugated ( attached ) to a specific binding member for hcv . &# 34 ; specific binding member &# 34 ; as used herein means a member of a specific binding pair . that is , two different molecules where one of the molecules through chemical or physical means specifically binds to the second molecule . in addition to being an antibody member of a specific binding pair for hcv , the indicator reagent also can be a member of any specific binding pair , including either hapten - anti - hapten systems such as biotin or anti - biotin , avidin or biotin , a carbohydrate or a lectin , a complementary nucleotide sequence , an effector or a receptor molecule , an enzyme cofactor and an enzyme , an enzyme inhibitor or an enzyme , and the like . an immunoreactive specific binding member can be an antibody , an antigen , or an antibody / antigen complex that is capable of binding either to hcv as in a sandwich assay , to the capture reagent as in a competitive assay , or to the ancillary specific binding member as in an indirect assay . the various &# 34 ; signal generating compounds &# 34 ; ( labels ) contemplated include chromogens , catalysts such as enzymes , luminescent compounds such as fluorescein and rhodamine , chemiluminescent compounds , radioactive elements , and direct visual labels . examples of enzymes include alkaline phosphatase , horseradish peroxidase , beta - galactosidase , and the like . the selection of a particular label is not critical , but it will be capable of producing a signal either by itself or in conjunction with one or more additional substances . the various &# 34 ; signal generating compounds &# 34 ; ( labels ) contemplated include chromogens , catalysts such as enzymes , luminescent compounds such as fluorescein and rhodamine , chemiluminescent compounds such as acridinium , phenanthridinium and dioxetane compounds , radioactive elements , and direct visual labels . examples of enzymes include alkaline phosphatase , horseradish peroxidase , beta - galactosidase , and the like . the selection of a particular label is not critical , but it will be capable of producing a signal either by itself or in conjunction with one or more additional substances . other embodiments which utilize various other solid phases also are contemplated and are within the scope of this invention . for example , ion capture procedures for immobilizing an immobilizable reaction complex with a negatively charged polymer , described in co - pending u . s . patent application ser . no . 150 , 278 corresponding to ep publication 0326100 , and u . s . patent application ser . no . 375 , 029 ( ep publication no . 0406473 ) both of which enjoy common ownership and are incorporated herein by reference , can be employed according to the present invention to effect a fast solution - phase immunochemical reaction . an immobilizable immune complex is separated from the rest of the reaction mixture by ionic interactions between the negatively charged poly - anion / immune complex and the previously treated , positively charged porous matrix and detected by using various signal generating systems previously described , including those described in chemiluminescent signal measurements as described in co - pending u . s . patent application ser . no . 921 , 979 corresponding to epo publication no . 0 273 , 115 , which enjoys common ownership and which is incorporated herein by reference . also , the methods of the present invention can be adapted for use in systems which utilize microparticle technology including in automated and semi - automated systems wherein the solid phase comprises a microparticle . such systems include those described in pending u . s . patent application ser . nos . 425 , 651 and 425 , 643 , which correspond to published epo applications nos . ep 0 425 633 and ep 0 424 634 , respectively , which are incorporated herein by reference . the use of scanning probe microscopy ( spm ) for immunoassays also is a technology to which the monoclonal antibodies of the present invention are easily adaptable . in scanning probe microscopy , in particular in atomic force microscopy , the capture phase , for example , at least one of the monoclonal antibodies of the invention , is adhered to a solid phase and a scanning probe microscope is utilized to detect antigen / antibody complexes which may be present on the surface of the solid phase . the use of scanning tunnelling microscopy eliminates the need for labels which normally must be utilized in many immunoassay systems to detect antigen / antibody complexes . such a system is described in pending u . s . patent application ser . no . 662 , 147 , which enjoys common ownership and is incorporated herein by reference . the use of spm to monitor specific binding reactions can occur in many ways . in one embodiment , one member of a specific binding partner ( analyte specific substance which is the monoclonal antibody of the invention ) is attached to a surface suitable for scanning . the attachment of the analyte specific substance may be by adsorption to a test piece which comprises a solid phase of a plastic or metal surface , following methods known to those of ordinary skill in the art . or , covalent attachment of a specific binding partner ( analyte specific substance ) to a test piece which test piece comprises a solid phase of derivatized plastic , metal , silicon , or glass may be utilized . covalent attachment methods are known to those skilled in the art and include a variety of means to irreversibly link specific binding partners to the test piece . if the test piece is silicon or glass , the surface must be activated prior to attaching the specific binding partner . activated silane compounds such as triethoxy amino propyl silane ( available from sigma chemical co ., st . louis , mo . ), triethoxy vinyl silane ( aldrich chemical co ., milwaukee , wis . ), and ( 3 - mercapto - propyl )- trimethoxy silane ( sigma chemical co ., st . louis , mo .) can be used to introduce reactive groups such as amino -, vinyl , and thiol , respectively . such activated surfaces can be used to link the binding partner directly ( in the cases of amino or thiol ) or the activated surface can be further reacted with linkers such as glutaraldehyde , bis ( succinimidyl ) suberate , sppd 9 succinimidyl 3 -[ 2 - pyridyldithio ] propionate ), smcc ( succinimidyl - 4 -[ n - maleimidomethyl ] cyclohexane - 1 - carboxylate ), siab ( succinimidyl [ 4 - iodoacetyl ] aminobenzoate ), and smpb ( succinimidyl 4 -[ 1 - maleimidophenyl ] butyrate ) to separate the binding partner from the surface . the vinyl group can be oxidized to provide a means for covalent attachment . it also can be used as an anchor for the polymerization of various polymers such as poly acrylic acid , which can provide multiple attachment points for specific binding partners . the amino surface can be reacted with oxidized dextrans of various molecular weights to provide hydrophilic linkers of different size and capacity . examples of oxidizable dextrans include dextran t - 40 ( molecular weight 40 , 000 daltons ), dextran t - 110 ( molecular weight 110 , 000 daltons ), dextran t - 500 ( molecular weight 500 , 000 daltons ), dextran t - 2m ( molecular weight 2 , 000 , 000 daltons ) ( all of which are available from pharmacia , location ), or ficoll ( molecular weight 70 , 000 daltons ( available from sigma chemical co ., st . louis , mo .). also , polyelectrolyte interactions may be used to immobilize a specific binding partner on a surface of a test piece by using techniques and chemistries described by pending u . s . patent application ser . no . 150 , 278 , filed jan . 29 , 1988 , and ser . no . 375 , 029 , filed jul . 7 , 1989 , each of which enjoys common ownership and each of which is incorporated herein by reference . the preferred method of attachment is by covalent means . following attachment of a specific binding member , the surface may be further treated with materials such as serum , proteins , or other blocking agents to minimize non - specific binding . the surface also may be scanned either at the site of manufacture or point of use to verify its suitability for assay purposes . the scanning process is not anticipated to alter the specific binding properties of the test piece . various other assay formats may be used , including &# 34 ; sandwich &# 34 ; immunoassays and competitive probe assays . for example , the monoclonal antibodies produced from the proteins of the present invention can be employed in various assay systems to determine the presence , if any , of hcv proteins in a test sample . fragments of these monoclonal antibodies provided also may be used . for example , in a first assay format , a polyclonal or monoclonal anti - hcv antibody or fragment thereof , or a combination of these antibodies , which has been coated on a solid phase , is contacted with a test sample which may contain hcv proteins , to form a mixture . this mixture is incubated for a time and under conditions sufficient to form antigen / antibody complexes . then , an indicator reagent comprising a monoclonal or a polyclonal antibody or a fragment thereof , which specifically binds to the hcv fragment , or a combination of these antibodies , to which a signal generating compound has been attached , is contacted with the antigen / antibody complexes to form a second mixture . this second mixture then is incubated for a time and under conditions sufficient to form antibody / antigen / antibody complexes . the presence of hcv antigen present in the test sample and captured on the solid phase , if any , is determined by detecting the measurable signal generated by the signal generating compound . the amount of hcv antigen present in the test sample is proportional to the signal generated . alternatively , a polyclonal or monoclonal anti - hcv antibody or fragment thereof , or a combination of these antibodies which is bound to a solid support , the test sample and an indicator reagent comprising a monoclonal or polyclonal antibody or fragments thereof , which specifically binds to hcv antigen , or a combination of these antibodies to which a signal generating compound is attached , are contacted to form a mixture . this mixture is incubated for a time and under conditions sufficient to form antibody / antigen / antibody complexes . the presence , if any , of hcv proteins present in the test sample and captured on the solid phase is determined by detecting the measurable signal generated by the signal generating compound . the amount of hcv proteins present in the test sample is proportional to the signal generated . in another alternate assay format , one or a combination of one or more monoclonal antibodies of the invention can be employed as a competitive probe for the detection of antibodies to hcv protein . for example , hcv proteins , either alone or in combination , can be coated on a solid phase . a test sample suspected of containing antibody to hcv antigen then is incubated with an indicator reagent comprising a signal generating compound and at least one monoclonal antibody of the invention for a time and under conditions sufficient to form antigen / antibody complexes of either the test sample and indicator reagent to the solid phase or the indicator reagent to the solid phase . the reduction in binding of the monoclonal antibody to the solid phase can be quantitatively measured . a measurable reduction in the signal compared to the signal generated from a confirmed negative nanb hepatitis test sample indicates the presence of anti - hcv antibody in the test sample . in yet another detection method , each of the monoclonal antibodies of the present invention can be employed in the detection of hcv antigens in fixed tissue sections , as well as fixed cells by immunohistochemical analysis . in addition , these monoclonal antibodies can be bound to matrices similar to cnbr - activated sepharose and used for the affinity purification of specific hcv proteins from cell cultures , or biological tissues such as blood and liver . the monoclonal antibodies of the invention can also be used for the generation of chimeric antibodies for therapeutic use , or other similar applications . the monoclonal antibodies or fragments thereof can be provided individually to detect hcv antigens . combinations of the monoclonal antibodies ( and fragments thereof ) provided herein also may be used together as components in a mixture or &# 34 ; cocktail &# 34 ; of at least one anti - hcv antibody of the invention with antibodies to other hcv regions , each having different binding specificities . thus , this cocktail can include the monoclonal antibodies of the invention which are directed to hcv proteins and other monoclonal antibodies to other antigenic determinants of the hcv genome . the polyclonal antibody or fragment thereof which can be used in the assay formats should specifically bind to a specific hcv region or other hcv proteins used in the assay . the polyclonal antibody used preferably is of mammalian origin ; human , goat , rabbit or sheep anti - hcv polyclonal antibody can be used . most preferably , the polyclonal antibody is rabbit polyclonal anti - hcv antibody . the polyclonal antibodies used in the assays can be used either alone or as a cocktail of polyclonal antibodies . since the cocktails used in the assay formats are comprised of either monoclonal antibodies or polyclonal antibodies having different hcv specificity , they would be useful for diagnosis , evaluation and prognosis of hcv infection , as well as for studying hcv protein differentiation and specificity . in another assay format , the presence of antibody and / or antigen to hcv can be detected in a simultaneous assay , as follows . a test sample is simultaneously contacted with a capture reagent of a first analyte , wherein said capture reagent comprises a first binding member specific for a first analyte attached to a solid phase and a capture reagent for a second analyte , wherein said capture reagent comprises a first binding member for a second analyte attached to a second solid phase , to thereby form a mixture . this mixture is incubated for a time and under conditions sufficient to form capture reagent / first analyte and capture reagent / second analyte complexes . these so - formed complexes then are contacted with an indicator reagent comprising a member of a binding pair specific for the first analyte labelled with a signal generating compound and an indicator reagent comprising a member of a binding pair specific for the second analyte labelled with a signal generating compound to form a second mixture . this second mixture is incubated for a time and under conditions sufficient to form capture reagent / first analyte / indicator reagent complexes and capture reagent / second analyte / indicator reagent complexes . the presence of one or more analytes is determined by detecting a signal generated in connection with the complexes formed on either or both solid phases as an indication of the presence of one or more analytes in the test sample . in this assay format , proteins derived from human expression systems may be utilized as well as monoclonal antibodies produced from the proteins derived from the mammalian expression systems as disclosed herein . such assay systems are described in greater detail in pending u . s . patent application ser . no . 07 / 574 , 821 entitled simultaneous assay for detecting one or more analytes , filed aug . 29 , 1990 , which enjoys common ownership and is incorporated herein by reference . in yet other assay formats , recombinant proteins may be utilized to detect the presence of anti - hcv in test samples . for example , a test sample is incubated with a solid phase to which at least one recombinant protein has been attached . these are reacted for a time and under conditions sufficient to form antigen / antibody complexes . following incubation , the antigen / antibody complex is detected . indicator reagents may be used to facilitate detection , depending upon the assay system chosen . in another assay format , a test sample is contacted with a solid phase to which a recombinant protein produced as described herein is attached and also is contacted with a monoclonal or polyclonal antibody specific for the protein , which preferably has been labelled with an indicator reagent . after incubation for a time and under conditions sufficient for antibody / antigen complexes to form , the solid phase is separated from the free phase , and the label is detected in either the solid or free phase as an indication of the presence of hcv antibody . other assay formats utilizing the proteins of the present invention are contemplated . these include contacting a test sample with a solid phase to which at least one recombinant protein produced in the mammalian expression system has been attached , incubating the solid phase and test sample for a time and under conditions sufficient to form antigen / antibody complexes , and then contacting the solid phase with a labelled recombinant antigen . assays such as this and others are described in pending u . s . patent application ser . no . 07 / 787 , 710 , which enjoys common ownership and is incorporated herein by reference . while the present invention discloses the preference for the use of solid phases , it is contemplated that the proteins of the present invention can be utilized in non - solid phase assay systems . these assay systems are known to those skilled in the art , and are considered to be within the scope of the present invention . the present invention will now be described by way of examples , which are meant to illustrate , but not to limit , the spirit and scope of the invention . rna isolated from the serum or plasma of a chimpanzee ( designated as &# 34 ; co &# 34 ;) experimentally infected with hcv , or an hcv seropositive human patient ( designated as &# 34 ; lg &# 34 ;) was transcribed to cdna using reverse transcriptase employing either random hexamer primers or specific anti - sense primers derived from the prototype hcv - 1 sequence . the sequence has been reported by choo et al . ( choo et al ., proc . nat &# 39 ; l . acad . sci . usa 88 : 2451 - 2455 [ 1991 ], and is available through genbank data base , accession no . m62321 ). this cdna then was amplified using pcr and amplitaq ® dna polymerase . ( available in the gene amp kit ® from perkin elmer cetus , norwalk , conn . 06859 ) employing either a second sense primer located approximately 1000 - 2000 nucleotides upstream of the specific antisense primer or a pair of sense and antisense primers flanking a 1000 - 2000 nucleotide fragment of hcv . after 25 to 35 cycles of amplification following standard procedures known in the art , an aliquot of this reaction mixture was subjected to nested pcr ( or &# 34 ; pcr - 2 &# 34 ;), wherein a pair of sense and antisense primers located internal to the original pair of pcr primers was employed to further amplify hcv gene segments in quantities sufficient for analysis and subcloning , utilizing endonuclease recognition sequences present in the second set of pcr primers . in this manner , seven adjacent hcv dna fragments were generated which then could be assembled using the generic cloning strategy presented and described in fig1 . the location of the specific primers used in this manner are presented in table 1 and are numbered according to the hcv - 1 sequence reported by choo et al ( genbank data base , accession no . m62321 ). prior to assembly , the dna sequence of each of the individual fragments was determined and translated into the genomic amino acid sequences presented in sequence id . no . 1 and 2 , respectively , for co and lg , respectively . comparison of the genomic polypeptide of co with that of hcv - 1 demonstrated 98 amino acid differences . comparison of the genomic polypeptide of co with that of lg . demonstrated 150 amino acid differences . comparison of the genomic polypeptide of lg with that of hcv - 1 demonstrated 134 amino acid differences . expression of the hcv e2 protein as a fusion with the amyloid precursor protein ( app ) the hcv e2 protein from co developed as described in example 1 was expressed as a fusion with the amyloid precursor protein ( app ). app has been described by kang et al ., nature 325 : 733 - 736 ( 1987 ). briefly , hcv amino acids 384 - 749 of the co isolate were used to replace the majority of the app coding sequence as demonstrated in fig2 . a hindiii - styl dna fragment representing the amino - terminal 66 amino acids and a bgiii - xbal fragment representing the carboxyl - terminal 105 amino acids of app were ligated to a pcr derived hcv fragment from co representing hcv amino acids 384 - 749 containing styl and bgiii restriction sites on its 5 &# 39 ; and 3 &# 39 ; ends , respectively . this app - hcv - e2 fusion gene cassette then was cloned into the commercially available mammalian expression vector prc / cmv shown in fig3 ( available from invitrogen , san diego , calif .) at the unique hindiii and xbal sites . after transformation into e . coli dh5α , a clone designated phcv - 162 was isolated , which placed the expression of the app - hcv - e2 fusion gene cassette under control of the strong cmv promotor . the complete nucleotide sequence of the mammalian expression vector phcv - 162 is presented in sequence id . no . 3 . translation of nucleotides 922 through 2535 results in the complete amino acid sequence of the app - hcv - e2 fusion protein expressed by phcv - 162 as presented in sequence id . no . 4 . a primary human embryonic kidney ( hek ) cell line transformed with human adenovirus type 5 , designated as hek - 293 , was used for all transfections and expression analyses . hek - 293 cells were maintained in minimum essential medium ( mem ) which was supplemented with 10 % fetal calf serum ( fcs ), penicillin and streptomycin . approximately 20 μg of purified dna from phcv - 162 was transfected into hek - 293 cells using the modified calcium phosphate protocol as reported by chen et al ., molecular and cellular biology 7 ( 8 ): 2745 - 2752 . ( 1987 ). the calcium - phosphate - dna solution was incubated on the hek - 293 cells for about 15 to 24 hours . the solution was removed , the cells were washed twice with mem media , and then the cells were incubated in mem media for an additional 24 to 48 hours . in order to analyze protein expression , the transfected cells were metabolically labelled with 100 μci / ml s - 35 methionine and cysteine for 12 to 18 hours . the culture media was removed and stored , and the cells were washed in mem media and then lysed in phosphate buffered saline ( pbs ) containing 1 % triton x - 100 ® ( available from sigma chemical co ., st . louis , mo . ), 0 . 1 % sodium dodecyl sulfate ( sds ), and 0 . 5 % deoxychloate , designated as pbs - tds . this cell lysate then was frozen at - 70 ° c . for 2 to 24 hours , thawed on ice and then clarified by centrifugation at 50 , 000 × g force for one hour at 4 ° c . standard radio - immunoprecipitation assays ( ripas ) then were conducted on those labelled cell lysates and / or culture medias . briefly , labelled cell lysates and / or culture medias were incubated with 2 to 5 μl of specific sera at 4 ° c . for one hour . protein - a sepharose then was added and the samples were further incubated for one hour at 4 ° c . with agitation . the samples were then centrifuged and the pellets washed several times with pbs - tds buffer . proteins recovered by immunoprecipitation were eluted by heating in an electrophoresis sample buffer ( 50 mm tris - hcl , ph 6 . 8 , 100 mm dithiothreitol [ dtt ], 2 % sds , 0 . 1 % bromophenol blue , and 10 % glycerol ) for five minutes at 95 ° c . the eluted proteins then were separated by sds polyacrylamide gels which were subsequently treated with a fluorographic reagent such as enlightening ® ( available from nen [ dupont ], boston , mass . ), dried under vacuum and exposed to x - ray film at - 70 ° c . with intensifying screens . fig4 presents a ripa analysis of phcv - 162 transfected hek cell lysate precipitated with normal human sera ( nhs ), a monoclonal antibody directed against app sequences which were replaced in this construct ( mab ), and an hcv antibody positive human sera (# 25 ). also presented in fig4 is the culture media ( supernatant ) precipitated with the same hcv antibody positive human sera (# 25 ). from fig4 it can be discerned that while only low levels of an hcv specific protein of approximately 75k daltons is detected in the culture media of hek - 293 cells transfected with phcv - 162 , high levels of intracellular protein expression of the app - hcv - e2 fusion protein of approximately 70k daltons is evident . in order to further characterize this app - hcv - e2 fusion protein , rabbit polyclonal antibody raised against synthetic peptides were used in a similar ripa , the results of which are illustrated in fig5 . as can be discerned from this figure , normal rabbit serum ( nrs ) does not precipitate the 70k dalton protein while rabbit sera raised against hcv amino acids 509 - 551 ( 6512 ), hcv amino acids 380 - 436 ( 6521 ), and app amino acids 45 - 62 ( anti - n - terminus ) are highly specific for the 70k dalton app - hcv - e2 fusion protein . in order to enhance secretion of this app - hcv - e2 fusion protein , another clone was generated which fused only the amino - terminal 66 amino acids of app , which contain the putative secretion signal sequences to the hcv - e2 sequences . in addition , a strongly hydrophobic sequence at the carboxyl - terminal end of the hcv - e2 sequence which was identified as a potential transmembrane spanning region was deleted . the resulting clone was designated as phcv - 167 and is schematically illustrated in fig2 . the complete nucleotide sequence of the mammalian expression vector phcv - 167 is presented in sequence id . no . 5 translation of nucleotides 922 through 2025 results in the complete amino acid sequence of the app - hcv - e2 fusion protein expressed by phcv - 167 as presented in sequence id . no . 6 . purified dna of phcv - 167 was transfected into hek - 293 cells and analyzed by ripa and polyacrylamide sds gels as described previously herein . fig6 presents the results in which a normal human serum sample ( nhs ) failed to recognize the app - hcv - e2 fusion protein present in either the cell lysate or the cell supernatant of hek - 293 cells transfected with phcv - 167 . the positive control hcv serum sample (# 25 ), however , precipitated an approximately 65k dalton app - hcv - e2 fusion protein present in the cell lysate of hek - 293 cells transfected with phcv - 167 . in addition , substantial quantities of secreted app - hcv - e2 protein of approximately 70k daltons was precipitated from the culture media by serum # 25 . digestion with endoglycosidase - h ( endo - h ) was conducted to ascertain the extent and composition of n - linked glycosylation in the app - hcv e2 fusion proteins expressed by phcv - 167 and phcv - 162 in hek - 293 cells . briefly , multiple aliquots of labelled cell lysates from phcv - 162 and phcv - 167 transfected hek - 293 cells were precipitated with human serum # 50 which contained antibody to hcv e2 as previously described . the protein - a sepharose pellet containing the immunoprecipitated protein - antibody complex was then resuspended in buffer ( 75 mm sodium acetate , 0 . 05 % sds ) containing or not containing 0 . 05 units per ml of endo - h ( sigma ). digestions were performed at 37 ° c . for 12 to 18 hours and all samples were analyzed by polyacrylamide sds gels as previously described . fig7 presents the results of endo - h digestion . carbon - 14 labelled molecular weight standards ( mw ) ( obtained from amersham , arlington heights , ill .) are common on all gels and represent 200k , 92 . 5k , 69k , 46k , 30k and 14 . 3k daltons , respectively . normal human serum ( nhs ) does not immunoprecipitate the app - hcv - e2 fusion protein expressed by either phcv - 162 or phcv - 167 , while human serum positive for hcv e2 antibody (# 50 ) readily detects the 72k dalton app - hcv - e2 fusion protein in phcv - 162 and the 65k dalton app - hcv e2 fusion protein in phcv - 167 . incubation of these immunoprecipitated proteins in the absence of endo - h (# 50 - endo - h ) does not significantly affect the quantity or mobility of either phcv - 162 or phcv - 167 expressed proteins . incubation in the presence of endo - h (# 50 + endo - h ), however , drastically reduces the mobility of the proteins expressed by phcv - 162 and phcv - 167 , producing a heterogenous size distribution . the predicted molecular weight of the non - glycosylated polypeptide backbone of phcv - 162 is approximately 59k daltons . endo - h treatment of phcv - 162 lowers the mobility to a minimum of approximately 44k daltons , indicating that the app - hcv - e2 fusion protein produced by phcv - 162 is proteolytically cleaved at the carboxyl - terminal end . a size of approximately 44k daltons is consistent with cleavage at or near hcv amino acid 720 . similarly , endo - h treatment of phcv - 167 lowers the mobility to a minimum of approximately 41k daltons , which compares favorably with the predicted molecular weight of approximately 40k daltons for the intact app - hcv - e2 fusion protein expressed by phcv - 167 . radio - immunoprecipitation assay ( ripa ) and polyacrylamide sds gel analysis previously described was used to screen numerous serum samples for the presence of antibody directed against hcv e2 epitopes . hek - 293 cells transfected with phcv - 162 were metabolically labelled and cell lysates prepared as previously described . in addition to ripa analysis , all serum samples were screened for the presence of antibodies directed against specific hcv recombinant antigens representing distinct areas of the hcv genome using the abbott matrix ® system . ( available from abbott laboratories , abbott park , ill . 60064 , u . s . pat . no . 5 , 075 , 077 ). in the matrix data presented in tables 2 through 7 , c100 yeast represents the ns4 region containing hcv amino acids 1569 - 1930 , c100 e . coli represents hcv amino acids 1676 - 1930 , ns3 represents hcv amino acids 1192 - 1457 , and core represents hcv amino acids 1 - 150 . fig8 presents a representative ripa result obtained using phcv - 162 cell lysate to screen hcv antibody positive american blood donors and transfusion recipients . table 2 summarizes the antibody profile of these various american blood samples , with seven of seventeen ( 41 %) samples demonstrating hcv e2 antibody . genomic variability in the e2 region has been demonstrated between different hcv isolates , particularly in geographically distinct isolates which may lead to differences in antibody responses . we therefore screened twenty - six japanese volunteer blood donors and twenty spanish hemodialysis patients previously shown to contain hcv antibody for the presence of specific antibody to the app - hcv e2 fusion protein expressed by phcv - 162 . fig9 and 10 present the ripa analysis on twenty - six japanese volunteer blood donors . positive control human sera (# 50 ) and molecular weight standards ( mw ) appear in both figures in which the specific immunoprecipitation of the approximately 72k dalton app - hcv - e2 fusion protein is demonstrated for several of the serum samples tested . table 3 presents both the app - hcv - e2 ripa and abbott matrix ® results summarizing the antibody profiles of each of the twenty - six japanese samples tested . table 4 presents similar data for the twenty spanish hemodialysis patients tested . table 5 summarizes the ripa results obtained using phcv - 162 to detect hcv e2 specific antibody in these various samples . eighteen of twenty - six ( 69 %) japanese volunteers blood donors , fourteen of twenty ( 70 %) spanish hemodialysis patients , and seven of seventeen ( 41 %) american blood donors or transfusion recipients demonstrated a specific antibody response against the hcv e2 fusion protein . the broad immunoreactivity demonstrated by the app - hcv - e2 fusion protein expressed by phcv - 162 suggests the recognition of conserved epitopes within hcv e2 . serial bleeds from five transfusion recipients which seroconverted to hcv antibody were also screened using the app - hcv - e2 fusion protein expressed by phcv - 162 . this analysis was conducted to ascertain the time interval after exposure to hcv at which e2 specific antibodies can be detected . table 6 presents one such patient ( an ) who seroconverted to ns3 at 154 days post transfusion ( dpt ). antibodies to hcv e2 were not detected by ripa until 271 dpt . table 7 presents another such patient ( wa ), who seroconverted to core somewhere before 76 dpt and was positive for hcv e2 antibodies on the next available bleed date ( 103 dpt ). table 8 summarizes the serological results obtained from these five transfusion recipients indicating ( a ) some general antibody profile at seroconversion ( ab status ); ( b ) the days post transfusion at which an elisa test would most likely detect hcv antibody ( 2 . 0 gen ); ( c ) the samples in which hcv e2 antibody was detected by ripa ( e2 ab status ); and ( d ) the time interval covered by the bleed dates tested ( samples tested ). the results indicate that antibody to hcv e2 , as detected in the ripa procedure described here , appears after seroconversion to at least one other hcv marker ( core , ns3 , c100 , etc .) and is persistent in nature once it appears . in addition , the absence of antibody to the structural gene core appears highly correlated with the absence of detectable antibody to e2 , another putative structural antigen . further work is ongoing to correlate the presence or absence of hcv gene specific antibodies with progression of disease and / or time interval since exposure to hcv viral antigens . expression of hcv e1 and e2 using human growth hormone secretion signal hcv dna fragments representing hcv e1 ( hcv amino acids 192 to 384 ) and hcv e2 ( hcv amino acids 384 - 750 and 384 - 684 ) were generated from the co isolate using pcr as described in example 2 . an eco ri restriction site was used to attach a synthetic oligonucleotide encoding the human growth hormone ( hgh ) secretion signal ( blak et al , oncogene , 3 129 - 136 , 1988 ) at the 5 &# 39 ; end of these hcv sequence . the resulting fragment was then cloned into the commercially available mammalian expression vector pcdna - i , ( available from invitrogen , san diego , calif .) illustrated in fig1 . upon transformation into e . coli mc1061 / p3 , the resulting clones place the expression of the cloned sequence under control of the strong cmv promoter . following the above outlined methods , a clone capable of expressing hcv - e1 ( hcv amino acids 192 - 384 ) employing the hgh secretion signal at the extreme amino - terminal end was isolated . the clone was designated phcv - 168 and is schematically illustrated in fig1 . similarly , clones capable of expressing hcv e2 ( hcv amino acids 384 - 750 or 384 - 684 ) employing the hgh secretion signal were isolated , designated phcv - 169 and phvc - 170 respectively and illustrated in fig1 . the complete nucleotide sequence of the mammalian expression vectors phcv - 168 , phcv - 169 , and phcv - 170 are presented in sequence id . no . 7 , 9 , and 11 respectively . translation of nucleotides 2227 through 2913 results in the complete amino acid sequence of the hgh - hcv - e1 fusion protein expressed by phcv - 168 as presented in sequence id . no . 8 . translation of nucleotides 2227 through 3426 results in the complete amino acid sequence of the hgh - hcv - e2 fusion protein expressed by phcv - 169 as presented in sequence id . no . 10 . translation of nucleotides 2227 through 3228 results in the complete amino acid sequence of the hgh - hcv - e2 fusion protein expressed by phcv - 170 as presented in sequence id . no . 12 . purified dna from phcv - 168 , phcv - 169 , and phcv - 170 was transfected into hek - 293 cells which were then metabolically labelled , cell lysates prepared , and ripa analysis performed as described previously herein . seven sera samples previously shown to contain antibodies to the app - hcv - e2 fusion protein expressed by phcv - 162 were screened against the labelled cell lysates of phcv - 168 , phcv - 169 , and phcv - 170 . fig1 presents the ripa analysis for phcv - 168 and demonstrated that five sera containing hcv e2 antibodies also contain hcv e1 antibodies directed against as approximately 33k dalton hgh - hcv - e1 fusion protein (# 25 , # 50 , 121 , 503 , and 728 ), while two other sera do not contain those antibodies ( 476 and 505 ). fig1 presents the ripa results obtained when the same sera indicated above were screened against the labelled cell lysates of either phcv - 169 or phcv - 170 . all seven hcv e1 antibody positive sera detected two protein species of approximately 70k and 75k daltons in cells transfected with phcv - 168 . these two different hgh - hcv - e2 protein species could result from incomplete proteolytic cleavage of the hcv e2 sequence at the carboxyl - terminal end ( at or near hcv amino acid 720 ) or from differences in carbohydrate processing between the two species . all seven hcv e2 antibody positive sera detected a single protein species of approximately 62k daltons for the hgh - hcv - e2 fusion protein expressed by phcv - 170 . table 9 summarizes the serological profile of six of the seven hcv e2 antibody positive sera screened against the hgh - hcv - e1 fusion protein expressed by phcv - 170 . further work is ongoing to correlate the presence or absence of hcv gene specific antibodies with progression of disease and / or time interval since exposure to hcv viral antigens . clones phcv - 167 and phcv - 162 have been deposited at the american type culture collection , 12301 parklawn drive , rockville , md ., 20852 , as of jan . 17 , 1992 under the terms of the budapest treaty , and accorded the following atcc designation numbers : clone phcv - 167 was accorded atcc deposit number 68893 and clone phcv - 162 was accorded atcc deposit number 68894 . clones phcv - 168 , phcv - 169 and phcv - 170 have been deposited at the american type culture collection , 12301 parklawn drive , rockville , md ., 20852 , as of jan . 26 , 1993 under the terms of the budapest treaty , and accorded the following atcc designation numbers : clone phcv - 168 was accorded atcc deposit number 69228 , clone phcv - 169 was accorded atcc deposit number 69229 and clone phcv - 170 was accorded atcc deposit number 69230 . the designated deposits will be maintained for a period of thirty ( 30 ) years from the date of deposit , or for five ( 5 ) years after the last request for the deposit ; or for the enforceable life of the u . s . patent , whichever is longer . these deposits and other deposited materials mentioned herein are intended for convenience only , and are not required to practice the invention in view of the descriptions herein . the hcv cdna sequences in all of the deposited materials are incorporated herein by reference . other variations of applications of the use of the proteins and mammalian expression systems provided herein will be apparent to those skilled in the art . accordingly , the invention is intended to be limited only in accordance with the appended claims . table 1______________________________________frag - pcr - 1 primers pcr - 2 primersment sense antisense sense antisense______________________________________1 1 - 17 1376 - 1400 14 - 31 1344 - 13642 1320 - 1344 2332 - 2357 1357 - 1377 2309 - 23273 2288 - 2312 3245 - 3269 2322 - 2337 3224 - 32424 3178 - 3195 5303 - 5321 3232 - 3252 5266 - 52895 5229 - 5249 6977 - 6996 5273 - 5292 6940 - 69626 6907 - 6925 8221 - 8240 6934 - 6954 8193 - 82167 8175 - 8194 9385 - 9401 8199 - 8225 9363 - 9387______________________________________ table 2______________________________________american hcv positive sera c100 c100 yeast e . coli ns3 core e2sample s / co s / co s / co s / co ripa______________________________________ 22 0 . 31 1 . 09 1 . 72 284 . 36 + 32 0 . 02 0 . 10 7 . 95 331 . 67 - 35 0 . 43 0 . 68 54 . 61 2 . 81 - 37 136 . 24 144 . 29 104 . 13 245 . 38 + 50 101 . 04 133 . 69 163 . 65 263 . 72 + 108 39 . 07 34 . 55 108 . 79 260 . 47 - 121 1 . 28 4 . 77 172 . 65 291 . 82 + 128 0 . 06 0 . 06 0 . 87 298 . 49 - 129 0 . 00 0 . 02 107 . 11 0 . 00 - 142 8 . 45 8 . 88 73 . 93 2 . 32 - 156 0 . 45 0 . 14 0 . 67 161 . 84 - 163 1 . 99 3 . 26 11 . 32 24 . 36 - mi 89 . 9 118 . 1 242 . 6 120 . 4 - ke 167 . 2 250 . 9 0 . 8 0 . 3 - wa 164 . 4 203 . 3 223 . 9 160 . 9 + pa 50 . 6 78 . 8 103 . 8 78 . 0 + an 224 . 8 287 . 8 509 . 9 198 . 8 + ______________________________________ table 3______________________________________japanese hcv positive positive blood donors c100 c100 yeast e . coli ns3 core e2sample s / co s / co s / co s / co ripa______________________________________410 86 . 33 93 . 59 9 . 68 257 . 82 + 435 0 . 18 0 . 18 0 . 69 39 . 25 + 441 0 . 20 0 . 09 0 . 17 6 . 51 - 476 0 . 37 1 . 29 144 . 66 302 . 35 + 496 39 . 06 37 . 95 2 . 78 319 . 99 - 560 1 . 08 0 . 68 3 . 28 26 . 59 - 589 0 . 06 1 . 28 117 . 82 224 . 23 + 620 0 . 17 1 . 37 163 . 41 256 . 64 + 622 123 . 46 162 . 54 154 . 67 243 . 44 + 623 23 . 46 26 . 55 143 . 72 277 . 24 + 633 0 . 01 0 . 43 161 . 84 264 . 02 + 639 1 . 40 2 . 23 12 . 15 289 . 80 + 641 0 . 01 0 . 08 8 . 65 275 . 00 + 648 - 0 . 00 0 . 03 0 . 79 282 . 64 + 649 97 . 00 127 . 36 147 . 46 194 . 73 + 657 4 . 12 6 . 33 141 . 04 256 . 57 + 666 0 . 14 0 . 24 5 . 90 60 . 82 - 673 72 . 64 90 . 11 45 . 31 317 . 66 + 677 0 . 05 0 . 23 2 . 55 99 . 67 - 694 86 . 72 87 . 18 45 . 43 248 . 80 + 696 0 . 02 - 0 . 02 0 . 26 12 . 55 - 706 17 . 02 12 . 96 153 . 77 266 . 87 + 717 0 . 04 0 . 02 0 . 15 10 . 46 - 728 - 0 . 01 0 . 26 90 . 37 246 . 30 + 740 0 . 02 0 . 10 0 . 25 46 . 27 - 743 1 . 95 1 . 56 133 . 23 254 . 25 + ______________________________________ table 4______________________________________spanish hemodialysis patients c100 c100 yeast e . coli ns3 core e2sample s / co s / co s / co s / co ripa______________________________________ 1 0 . 0 0 . 3 188 . 6 - 0 . 0 - 2 129 . 3 142 . 8 165 . 4 201 . 0 + 3 113 . 7 128 . 5 154 . 5 283 . 3 + 5 130 . 6 143 . 8 133 . 4 186 . 1 + 6 56 . 2 63 . 4 93 . 6 32 . 0 + 7 0 . 0 0 . 2 72 . 1 211 . 5 + 8 156 . 7 171 . 9 155 . 1 227 . 0 + 9 65 . 3 78 . 9 76 . 1 102 . 6 + 10 136 . 7 149 . 3 129 . 4 190 . 2 + 11 0 . 0 0 . 7 155 . 7 272 . 4 + 12 1 . 0 1 . 9 143 . 6 210 . 6 + 13 0 . 0 0 . 3 111 . 2 91 . 1 - 14 1 . 1 3 . 1 94 . 7 214 . 8 - 15 45 . 9 66 . 1 106 . 3 168 . 2 + 16 36 . 3 68 . 8 149 . 3 0 . 1 - 17 121 . 0 129 . 9 113 . 4 227 . 8 + 18 64 . 8 99 . 7 138 . 9 0 . 2 - 19 25 . 6 34 . 1 157 . 4 254 . 9 + 20 104 . 9 125 . 1 126 . 8 218 . 3 + 21 48 . 1 68 . 5 0 . 8 49 . 4 - ______________________________________ table 5______________________________________antibody response to hcv proteins c100 c100 yeast e . coli ns3 core e2 s / co s / co s / co s / co ripa______________________________________american 11 / 17 12 / 17 14 / 17 15 / 17 7 / 17blooddonorsspanish 16 / 20 16 / 20 19 / 20 17 / 20 14 / 20hemodialysispatientsjapanese 12 / 26 14 / 26 20 / 26 26 / 26 18 / 26blooddonors______________________________________ table 6______________________________________human transfusion recipient ( an ) days c100 c100post yeast e . coli ns3 core e2trans . s / co s / co s / co s / co ripa______________________________________ 29 1 . 8 1 . 9 8 . 9 1 . 1 - 57 0 . 4 0 . 3 1 . 2 0 . 4 - 88 0 . 3 0 . 3 0 . 4 0 . 7 - 116 0 . 1 0 . 2 0 . 5 0 . 2 - 154 0 . 3 0 . 7 65 . 3 0 . 8 - 179 18 . 0 21 . 5 445 . 6 1 . 5 - 271 257 . 4 347 . 2 538 . 0 3 . 1 + 376 240 . 0 382 . 5 513 . 5 139 . 2 + 742 292 . 9 283 . 7 505 . 3 198 . 1 + 1105 282 . 1 353 . 9 456 . 1 202 . 2 + 1489 224 . 8 287 . 8 509 . 9 198 . 8 + ______________________________________ table 7______________________________________human transfusion recipient ( wa ) days c100 c100post yeast e . coli ns3 core e2trans . s / co s / co s / co s / co ripa______________________________________ 43 0 . 1 0 . 6 0 . 4 1 . 2 - 76 0 . 1 0 . 1 0 . 9 72 . 7 - 103 0 . 0 0 . 6 1 . 4 184 . 4 + 118 3 . 7 3 . 7 1 . 9 208 . 7 + 145 83 . 8 98 . 9 12 . 3 178 . 0 + 158 142 . 1 173 . 8 134 . 3 185 . 2 + 174 164 . 4 203 . 3 223 . 9 160 . 9 + ______________________________________ table 8______________________________________human transfusion recipients samplesab status 2 . 0 gen e2 ab status tested______________________________________mi strong 78 dpt neg . 1 - 178 dptresponseke early c100 103 dpt neg . 1 - 166 dptwa early core 76 dpt pos . 103 - 173 1 - 173 dpt dptpa early c100 127 dpt pos . 1491 - 3644 1 - 3644 dpt dptan early 33c 179 dpt pos . 271 - 1489 1 - 1489 dpt dpt______________________________________ table 9______________________________________selected hcv e2 antibody positive samples c100 c100 yeast e . coli ns3 core e1sample s / co s / co s / co s / co ripa______________________________________ 50 101 . 04 133 . 69 163 . 65 263 . 72 + 121 1 . 28 4 . 77 172 . 65 291 . 82 + 503 113 . 7 128 . 5 154 . 5 283 . 3 + 505 130 . 6 143 . 8 133 . 4 186 . 1 - 476 0 . 37 1 . 29 144 . 66 302 . 35 - 728 - 0 . 01 0 . 26 90 . 37 246 . 30 + ______________________________________ __________________________________________________________________________seq . id . no . 1co10 20 30 40 50 60 70mstnpkpqrk tkrntnrrpq dvrfpgggqi vggvyllprr gprlgvratr ktsersqprg rrqpipkarr80 90 100 110 120 130 140pegrtwaqpg ypwplygneg cgwagwllsp rgsrpswgpt dprrrsrnlg kvidtltcgf adlmgyiplv150 160 170 180 190 200 210gaplggaara lahgvrvled gvnyatgnlp gcsfsiflla llscltvpas ayqvrnssgl yhvtndcpns220 230 240 250 260 270 280sivyeaadai lhtpgcvpcv regnasrcwv avtptvatrd gklpttqlrr hidllvgsat lcsalyvgdl290 300 310 320 330 340 350cgsvflvgql ftfsprrhwt tqdcncsiyp ghitghrmaw dmmmnwspta alvvaqllri pqaildmiag360 370 380 390 400 410 420ahwgvlagia yfsmvgnwak vlvvlllfag vdaethvtgg saghttaglv rllspgakqn iqlintngsw430 440 450 460 470 480 490hinstalncn eslntgwlag lfyhhkfnss gcperlascr rltdfaqggg pisyangsgl derpycwhyp500 510 520 530 540 550 560prpcgivpak svcgpvycft pspvvvgttd rsgaptyswg andtdvfvln ntrpplgnwf gctwmnstgf570 580 590 600 610 620 630tkvcgappcv iggvgnntll cptdcfrkhp eatysrcgsg pwitprcmvd ypyrlwhypc tinytifkyr640 650 660 670 680 690 700myvggvehrl eaacnwtrge rcdledrdrs elsplllstt qwqvlpcsft tlpalstgli hlhqnivdvq710 720 730 740 750 760 770ylygvgssia swaikweyvv llfllladar vcsclwmmll isqaeaalen lvilnaasla gthgfvsflv780 790 800 810 820 830 840ffcfawylkg rwvpgaayal ygiwplllll lalpqrayal dtevaascgg vvlvglmalt lspyykryis850 860 870 880 890 900 910wcmwwlqyfl trveaqlhvw vpplnvrggr davillmcav hptlvfditk lllaifgplw ilqasllkvp920 930 940 950 960 970 980yfvrvqgllr icalarkiag ghyvqmifik lgaltgtyvy nhltplrdwa hnglrdlava vepvvfsrme990 1000 1010 1020 1030 1040 1050tklitwgadt aacgdiingl pvsarrgqei llgpadgmvs kgwrllapit ayaqqtrgll gciitsltgr1060 1070 1080 1090 1100 1110 1120dknqvegevq ivstatqtfl atcingvcwt vyhgagtrti aspkgpviqm ytnvdqdlvg wpapqgsrsl1130 1140 1150 1160 1170 1180 1190tpctcgssdl ylvtrhadvi pvrrqgdsrg sllsprpisy lkgssggpll cpaghavglf raavctrgva1200 1210 1220 1230 1240 1250 1260kavdfipven lettmrspvf tdnssppavp qsfqvahlha ptgsgkstkv paayaaqgyk vlvlnpsvaa1270 1280 1290 1300 1310 120 1330tlgfgaymsk ahgvdpnirt gvrtittgsp itystygkfl adggcsggay diiicdechs tdatsilgig1340 1350 1360 1370 1380 1390 1400tvldqaetag arlvvlatat ppgsvtvphp nieevalstt geipfygkai plevikggrh lifchskkkc1410 1420 1430 1440 1450 1460 1470delaaklval ginavayyrg ldvsvipasg dvvvvstdal mtgftgdfdp vidcntcvtq tvdfsldptf1480 1490 1500 1510 1520 1530 1540tietttlpqd avsrtqrrgr tgrgkpgiyr fvapgerpsg mfdssvlcec ydagcawyel tpaettvrlr1550 1560 1570 1580 1590 1600 1610aymntpglpv cqdhlefweg vftglthida hflsqtkqsg enfpylvayq atvcaraqap ppswdqmwkc1620 1630 1640 1650 1660 1670 1680lirlkptlhg ptpliyrlga vqneitlthp vtkyimtcms anpevvtstw vlvggvlaal aayclstgcv1690 1700 1710 1720 1730 1740 1750vivgrivlsg kpaiipdrev lyqefdemee csqhlpyieq gmmlaeqfkq ealgllqtas rqaevitpav1760 1770 1780 1790 1800 1810 1820qtnwqkleaf wakhmwnfis gtqylaglst lpgnpaiasl maftaavtsp lttsqtllfn ilggwvaaql1830 1840 1850 1860 1870 1880 1890aapgaatafv gaglagaaig svglgkvlvd ilagygagva galvafkims gevpstedlv nllpailspg1900 1910 1920 1930 1940 1950 1960alvvgvvcaa ilrrhvgpge gavqwmnrli afasrgnhvs pthyvpesda aarvtailsn ltvtqllrrl1970 1980 1990 2000 2010 2020 2030hqwigsectt pcsgswlrdi wdwicevlsd fktwlkaklm pqlpgipfvs cqrgyrgvwr gdgimhtrch2040 2050 2060 2070 2080 2090 2100cgaeitghvk ngtmrivgpr tcrnmwsgtf pinayttgpc tplpapnykf alwrvsaeey veirrvgdfh2110 2120 2130 2140 2150 2160 2170yvsgmttdnl kcpcqipspe ffteldgvrl hrfappckpl lreevsfrvg lheypvgsql pcepepdvav2180 2190 2200 2210 2220 2230 2240ltsmltdpsh itaeaagrrl argsppsmas ssasqlsaps lkatcttnhd spdaeliean llwrqemggn2250 2260 2270 2280 2290 2300 2310itrvesenkv vildsfdplv aeederevsv paeilrksqr faralpvwar pdynppliet wkepdyeppv2320 2330 2340 2350 2360 2370 2380vhgcplpppr sppvppprkk rtvvltestl stalaelatk sfgssstsgi tgdntttsse papsgcppds2390 2400 2410 2420 2430 2440 2450dvesyssmpp legepgdpdf sdgswstvss gadtedvvcc smsyswtgal vtpcaaeeqk lpinalsnsl2460 2470 2480 2490 2500 2510 2520lrhhnlvyst tsrsacqrqk kvtfdrlqvl dshyqdvlke vkaaasrvka nllsveeacs ltpphsaksk2530 2540 2550 2560 2570 2580 2590fgygakdvrc harkavahin svwkdlleds vtpidttima knevfcvqpe kggrkparli vfpdlgvrvc2600 2610 2620 2630 2640 2650 2660ekmalydvvs klplavmgss ygfqyspgqr veflvqawks kktpmgfsyd trcfdstvte sdirteeaiy2670 2680 2690 2700 2710 2720 2730qccdldpqar vaikslterl yvggpltnsr gencgyrrcr asgvlttscg ntltcyikar aacraaglqd2740 2750 2760 2770 2780 2790 2800rtmlvcgddl vvicesagvq edaaslraft eamtrysapp gdppqpeydl elitscssnv svahdgagkr2810 2820 2830 2840 2850 2860 2870vyyltrdptt plaraaweta rhtpvnswlg niimfaptlw armilmthff svliardqfe qalnceiyga2880 2890 2900 2910 2920 2930 2940cysiepldlp piiqrlhgls afslhsyspg einrvaaclr klgvpplraw khrarsvrar llsrggraai2950 2960 2970 2980 2990 3000 3010cgkylfnwav rtkpkltpia aagrldlsgw ftagysggdi yhsvsharpr wswfclllla agvgiyllpnr . pep : __________________________________________________________________________seq . id . no . 2lg10 20 30 40 50 60 70mstnpkpqrk tkrntnrrpq dvkfpgggqi vggvyllprr gprlgvratr ktsersqprg rrqpipkarr80 90 100 110 120 130 140pegrtwaqpg ypwplygneg cgwagwllsp rgsrpswgpt dprrrsrnlg kvidtltcgf adlmgyiplv150 160 170 180 190 200 210gaplggaara lahgvrvled gvnyatgnlp gcsfsiflla llscltvpas ayqvrnssgl yhvtndcpns220 230 240 250 260 270 280sivyetadti lhspgcvpcv regntskcwv avaptvttrd gklpstqlrr hidllvgsat lcsalyvgdl290 300 310 320 330 340 350cgsvflvsql ftfsprrhwt tqdcncsiyp ghitghrmaw dmmmnwsptt alvvaqllri pqaildmiag360 370 380 390 400 410 420ahwgvlagia yfsmvgnwak vlvvlllfsg vdaatyttgg svartthgls slfsqgakqn iqlintngsw430 440 450 460 470 480 490hinrtalncn asldtgwvag lfyyhkfnss gcpermascr pladfdqgwg pisytngsgp ehrpycwhyp500 510 520 530 540 550 560pkpcgivpaq svcgpvycft pspvvvgttd ksgaptytwg sndtdvfvln ntrpppgnwf gctwmnssgf570 580 590 600 610 620 630tkvcgappcv iggagnntlh cptdcfrkhp eatysrcgsg pwitprclvh ypyrlwhypc tinytlfkvr640 650 660 670 680 690 700myvggvehrl evacnwtrge rcdlddrdrs elsplllstt qwqvlpcsft tlpalttgli hlhqnivdvq710 720 730 740 750 760 770ylygvgssiv swaikweyvi llfllladar icsclwmmll isqaeaalen lvllnaasla gthglvsflv780 790 800 810 820 830 840ffcfawylkg kwvpgvayaf ygmwpfllll lalpqrayal dtemaascgg vvlvglmalt lsphykryic850 860 870 880 890 900 910wcvwwlqyfl traeallhgw vpplnvrggr davillmcvv hpalvfditk lllavlgplw ilqtsllkvp920 930 940 950 960 970 980yfvrvqgllr icalarkmag ghyvqmvtik mgalagtyvy nhltplrdwa hnglrdlava vepvvfsqme990 1000 1010 1020 1030 1040 1050tklitwgadt aacgdiingl pvsarrgrei llgpadgmvs kgwrllapit ayaqqtrgll gciitsltgr1060 1070 1080 1090 1100 1110 1120dknqvegevq ivstaaqtfl atcingvcwt vyhgagtrti aspkgpviqm ytnvdrdlvg wpapqgarsl1130 1140 1150 1160 1170 1180 1190tpctcgssdl ylvtrhadvi pvrrrgdsrg sllsprpisy lkgssggpll cpaghavgif raavctrgva1200 1210 1220 1230 1240 1250 1260kavdfipves lettmrspvf tdnssppavp qsfqvahlha ptgsgkstkv paayaaqgyk vlvlnpsvaa1270 1280 1290 1300 1310 1320 1330tlgfgaymsk ahgidpnirt gvrtittgsp itystygkfl adggcsggay diiicdechs tdatsilgig1340 1350 1360 1370 1380 1390 1400tvldqaetag arlvvlatat ppgsvtvphp nieevalstt geipfygkai pleaikggrh lifchskkkc1410 1420 1430 1440 1450 1460 1470delaaklvtl ginavayyrg ldvsviptsg dvvvvatdal mtgftgdfds vidcntcvtq avdfsldptf1480 1490 1500 1510 1520 1530 1540tietttlpqd avsrtqrrgr tgrgkpgiyr fvapgerpsg mfdssvlcec ydagcawyel tpaettvrlr1550 1560 1570 1580 1590 1600 1610aymntpglpv cqdhlefweg vftglthida hflsqtkqsg enlpylvayq atvcaraqap ppswdqmmkc1620 1630 1640 1650 1660 1670 1680lirlkptlhg ptpllyrlga vqnevtlthp itkyimtcms adlevvtstw vlvggvlaal aayclstgcv1690 1700 1710 1720 1730 1740 1750vivgrivlsg kpaiipdrev lyrefdemee csqhlpyieq gmmlaeqfkq kalgllqtas hqaeviapav1760 1770 1780 1790 1800 1810 1820qtnwqrletf wakhmwnfis giqylaglst lpgnpaiasl maftaavtsp lttsqtllfn ilggwvaaql1830 1840 1850 1860 1870 1880 1890aapsaatafv gaglagaaig svglgkvlvd ilagygagva galvafkims gevpstedlv nllpailspg1900 1910 1920 1930 1940 1950 1960alvvgvvcaa ilrrhvgpge gavqwmnrli afasrgnhvs pthyvpgsda aarvtailss ltvtqllrrl1970 1980 1990 2000 2010 2020 2030hqwvssectt pcsgswlrdi wdwicevlsd fktwlkaklm pqlpgipfvs cqrgykgvwr gdgimhtrch2040 2050 2060 2070 2080 2090 2100cgaeiaghvk ngtmrivgpk tcrnmwsgtf pinayttgpc tplpapnykf alwrvsaeey veirqvgdfh2110 2120 2130 2140 2150 2160 2170yvtgmtadnl kcpcqvpspe ffteldgvrl hrfappckpl lrdevsfrvg lhdypvgsql pcepepdvav2180 2190 2200 2210 2220 2230 2240ltsmltdpsh itaetagrrl argsppsmas ssasqlsaps lkatcttnhd spdaellean llwrqenggn2250 2260 2270 2280 2290 2300 2310itrvesenkv vvldsfdplv aeederevsv paeilrksrr faqalpswar pdynppllet wkkpdyeppv2320 2330 2340 2350 2360 2370 2380vhgcplpppq sppvppprkk rtvvltestv ssalaelatk sfgssstsgi tgdntttsse papsvcppds2390 2400 2410 2420 2430 2440 2450daesyssmpp legepgdpdl sdgswstvss gadtedvvcc smsyswtgal itpcaaeeqk lpinalsnsl2460 2470 2480 2490 2500 2510 2520lrhhnlvyst tsrnaclrqk kvtfdrlqvl dnhyqdvlke vkaaaskvka nllsveeacs ltpphsarsk2530 2540 2550 2560 2570 2580 2590fgygakdvrc harkavshin svwkdlleds vtpidttima knevfcvqpe kggrkparli vfpdlgvrvc2600 2610 2620 2630 2640 2650 2660ekmalydvvs klplavmgss ygfqyspgqr veflvqawks kktpmgfsyd trcfdstvte sdirteeaiy2670 2680 2690 2700 2710 2720 2730qccdldpqar vaikslterl yvggpltnsr gencgyrrcr asgvlttscg ntltcyikar aacraaglqd2740 2750 2760 2770 2780 2790 2800ctmlvcgddl vvicesqgvq edaaslraft eamtrysapp gdppqpeydl elitpcssnv svahdgagkr2810 2820 2830 2840 2850 2860 2870vyyltrdptt plaraaweta rhtpvnswlg niimfaptlw armilmthff svliardqle qaldceiyga2880 2890 2900 2910 2920 2930 2940cysiepldlp piiqrlhgls afslhsyspg einrvaaclr klgvpplraw rhrarsvrar llsrggraai2950 2960 2970 2980 2990 3000 3010cgkylfnwav rtklkltpia aagqldlsgw ftagygggdi yhsvsrarpr wfwfclllla agvgiyllpnr . pep : __________________________________________________________________________seq . id . no . 3phcv . sub .-- 162circular sequence with junction at 729810 20 30 40 50 60 70gacggatcgg gagatctccc gatcccctat ggtcgactct cagtacaatc tgctctgatg ccgcatagtt80 90 100 110 120 130 140aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg cgagcaaaat ttaagctaca150 160 170 180 190 200 210acaaggcaag gcttgaccga caattgcatg aagaatctgc ttagggttag gcgttttgcg ctgcttcgcg220 230 240 250 260 270 280atgtacgggc cagatatacg cgttgacatt gattattgac tagttattaa tagtaatcaa ttacggggtc290 300 310 320 330 340 350attagttcat agcccatata tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg360 370 380 390 400 410 420cccaacgacc cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc430 440 450 460 470 480 490attgacgtca atgggtggac tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc500 510 520 530 540 550 560aagtacgccc cctattgagg tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta570 580 590 600 610 620 630tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac catggtgatg cggttttggc640 650 660 670 680 690 700agtacatcaa tgggcgtgga tagcggtttg actcacgggg atttccaagt ctccacccca ttgacgtcaa710 720 730 740 750 760 770tgggagtttg ttttggcacc aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg780 790 800 810 820 830 840caaatgggcg gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca850 860 870 880 890 900 910ctgcttaact ggcttatcga aattaatacg actcactata gggagaccgg aagctttgct ctagactgga920 930 940 950 960 970 980attcgggcgc gatgctgccc ggtttggcac tgctcctgct ggccgcctgg acggctcggg cgctggaggt990 1000 1010 1020 1030 1040 1050acccactgat ggtaatgctg gcctgctggc tgaaccccag attgccatgt tctgtggcag actgaacatg1060 1070 1080 1090 1100 1110 1120cacatgaatg tccagaatgg gaagtgggat tcagatccat cagggaccaa aacctgcatt gataccaagg1130 1140 1150 1160 1170 1180 1190aaaacccacgt caccggggga agtgccggcc acaccacggc tgggcttgtt cgtctccttt caccaggcgc1200 1210 1220 1230 1240 1250 1260caagcagaac atccaactga tcaacaccaa cggcagttgg cacatcaata gcacggcctt gaactgcaat1270 1280 1290 1300 1310 1320 1330gaaaagcctta acaccggctg gttagcaggg ctcttctatc accacaaaatt caactcttca ggttgtcctg1340 1350 1360 1370 1380 1390 1400agaggttggc cagctgccga cgccttaccg attttgccca gggcgggggt cctatcagtt acgccaacgg1410 1420 1430 1440 1450 1460 1470aagcggcctc gatgaacgcc cctactgctg gcactaccct ccaagacctt gtggcattgt gcccgcaaag1480 1490 1500 1510 1520 1530 1540agcgtgtgtg gcccggtta ttgcttcact cccagccccg tggtggtggg aacgaccgac aggtcgggcg1550 1560 1570 1580 1590 1600 1610cgcctaccta cagctggggt gcaaatgata cggatgtctt tgtccttaac aacaccaggc caccgctggg1620 1630 1640 1650 1660 1670 1680caattggttc ggttgcacct ggatgaactc aactggattc accaaagtgt gcggagcgcc cccttgtgtc1690 1700 1710 1720 1730 1740 1750atcggagggg tgggcaacaa caccttgctc tgccccactg attgcttccg caagcatccg gaagccacat1760 1770 1780 1790 1800 1810 1820actctcggtg cggctccggt ccctggatta cacccaggtg catggtcgac tacccgtata ggctttggca1830 1840 1850 1860 1870 1880 1890ctatccttgt accatcaatt acaccatatt caaagtcagg atgtacgtgg gaggggtcga gcacaggctg1900 1910 1920 1930 1940 1950 1960gaagcggcct gcaactggac gcggggcgaa cgctgtgatc tggaagacag ggacaggtcc gagctcagcc1970 1980 1990 2000 2010 2020 2030cgttactgct gtccaccacg cagtggcagg tccttccgtg ttctttcacg accctgccag ccttgtccac2040 2050 2060 2070 2080 2090 2100cggcctcatc cacctccacc agaacattgt ggacgtgcag tacttgtacg gggtagggtc aagcatcgcg2110 2120 2130 2140 2150 2160 2170tcctgggcta ttaagtggga gtacgacgtt ctcctgttcc ttctgcttgc agacgcgcgc gtttgctcct2180 2190 2200 2210 2220 2230 2240gcttgtggat gatgttactc atatcccaag cggaggcggc tttggagatc tctgaagtga agatggatgc2250 2260 2270 2280 2290 2300 2310agaattccga catgactcag gatatgaagt tcatcatcaa aaaattggtgt tctttgcaga agatgtgggt2320 2330 2340 2350 2360 2370 2380tcaaacaaag gtgcaatcat tggactcatg gtgggcggtg ttgtcatagc gacagtgatc gtcatcacct2390 2400 2410 2420 2430 2440 2450tggtgatgct gaagaagaaa cagtacacat ccattcatca tggtgtggtg gaggttgacg ccgctgtcac2460 2470 2480 2490 2500 2510 2520cccagaggag cgccacctgt ccaagatgca gcagaacggc tacgaaaatc caacctacaa gttctttgag2530 2540 2550 2560 2570 2580 2590cagatgcaga actagacccc cgccacagca gcctctgaag ttggacagca aaaccattgc ttcactaccc2600 2610 2620 2630 2640 2650 2660atcggtgtcc atttatagaa taatgtggga agaaacaaac ccgttttatg atttactcat tatcgccttt2670 2680 2690 2700 2710 2720 2730tgacagctgt gctgtaacac aagtagatgc ctgaacttga attaatccac acatcagtat tgtaatctat2740 2750 2760 2770 2780 2790 2800ctctctttac attttggtct ctatactaca ttattaatgg gttttgtgta ctgtaaagaa tttagctgta2810 2820 2830 2840 2850 2860 2870tcaaactagt gcatgaatag gccgctcgag catgcatcta gagggcccta ttctatagtg tcacctaaat2880 2890 2900 2910 2920 2930 2940gctcgctgat cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt2950 2960 2970 2980 2990 3000 3010ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat cgcattgtct3020 3030 3040 3050 3060 3070 3080gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg gggaggattg ggaagacaat3090 3100 3110 3120 3130 3140 3150agcaggcatg ctggggatgc ggtgggctct atggaaccag ctggggctcg aggggggatc cccacgcgcc3160 3170 3180 3190 3200 3210 3220ctgtagcggc gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc3230 3240 3250 3260 3270 3280 3290ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc cgtcaagctc3300 3310 3320 3330 3340 3350 3360taaatcgggg catcccttta gggttccgat ttagtgcttt acggcacctc gaccccaaaa aacttgatta3370 3380 3390 3400 3410 3420 3430gggtgatggt tcacgta6tg ggccatcgcc ctgatagacg gtttttcgcc tttactgagc actctttaat3440 3450 3460 3470 3480 3490 3500agtggactct tgttccaaaac tggaacaaca ctcaacccta tctcggtcta ttcttttgat ttataagatt3510 3520 3530 3540 3550 3560 3570tccatcgcca tgtaaaagtg ttacaattag cattaaatta cttctttata tgctactatt cttttggctt3580 3590 3600 3610 3620 3630 3640cgttcacggg gtgggtaccg agctcgaatt ctgtggaatg tgtgtcagtt agggtgtgga aagtccccag3650 3660 3670 3680 3690 3700 3710gctccccagg caggcagaag tatgcaaagc atgcatctca attagtcagc aaccaggtgt ggaaagtccc3720 3730 3740 3750 3760 3770 3780caggctcccc agcaggcaga agtatgcaaa gcatgcatct caattagtca gcaaccatag tcccgcccct3790 3800 3810 3820 3830 3840 3850aactccgccc atcccgcccc taactccgcc cagttccgcc cattctccgc cccatggctg actaattttt3860 3870 3880 3890 3900 3910 3920tttatttatg cagaggccga ggccgcctcg gcctctgagc tattccagaa gtagtgagga ggcttttttg3930 3940 3950 3960 3970 3980 3990gaggcctagg cttttgcaaa aagctcccgg gagcttggat atccattttc ggatctgatc aagagacagg4000 4010 4020 4030 4040 4050 4060atgaggatcg tttcgcatga ttgaacaaga tggattgcac gcaggttctc cggccgcttg ggtggagagg4070 4080 4090 4100 4110 4120 4130ctattcggct atgactgggc acaacagaca atcggctgct ctgatgccgc cgtgttccgg ctgtcagcgc4140 4150 4160 4170 4180 4190 4200aggggcgccc ggttcttttt gtcaagaccg acctgtccgg tgccctgaat gaactgcagg acgaggcagc4210 4220 4230 4240 4250 4260 4270gcggctatcg tggctggcca cgacgggcgt tccttgcgca gctgtgctcg acgttgtcac tgaagcggga4280 4290 4300 4310 4320 4330 4340agggactggc tgctattggg cgaagtgccg gggcaggatc tcctgtcatc tcaccttgct cctgccgaga4350 4360 4370 4380 4390 4400 4410aagtatccat catggctgat gcaatgcggc ggctgcatac gcttgatccg gctacctgcc cattcgacca4420 4430 4440 4450 4460 4470 4480ccaagcgaaa catcgcatcg agcgagcacg tactcggatg gaagccggtc ttgtcgatca ggatgatctg4490 4500 4510 4520 4530 4540 4550gacgaagagc atcaggggct cgcgccagcc gaactgttcg ccaggctcaa ggcgcgcatg cccgacggcg4560 4570 4580 4590 4600 4610 4620aggatctcgt cgtgacccat ggcgatgcct gcttgccgaa tatcatggtg gaaaatggcc gcttttctgg4630 4640 4650 4660 4670 4680 4690attcatcgac tgtggccggc tgggtgtggc ggaccgctat caggacatag cgttggctac ccgtgatatt4700 4710 4720 4730 4740 4750 4760gctgaagagc ttggcggc6a atgggctgac cgcttcctcg tgcaaacgg tatcgccgct cccgattcgc4770 4780 4790 4800 4810 4820 4830agcgcatcgc cttctatcgc cttcttgacg agttcttctg agcgggactc tggggttcga aatgaccgac4840 4850 4860 4870 4880 4890 4900caagcgacgc ccaacctgcc atcacgagat ttcgattcca ccgccgcctt ctatgaaagg ttgggcttcg4910 4920 4930 4940 4950 4960 4970gaatcgtttt ccgggacgcc ggctggatga tcctccagcg cggggatctc atgctggagt tcttcgccca4980 4990 5000 5010 5020 5030 5040ccccaacttg tttattgcag cttataatgg ttacaaataa agcaatagca tcacaaattt cacaaataaa5050 5060 5070 5080 5090 5100 5110gcattttttt cactgcattc tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctggatcc5120 5130 5140 5150 5160 5170 5180cgtcgacctc gagagcttgg cgtaatcatg gtcatagctg aacctgtgtg aaaattgtta tccgctcaca5190 5200 5210 5220 5230 5240 5250attccacaca acatacgagc cggaagcata aagtgtaaag cctggggtgc ctaatgagtg agctaactca5260 5270 5280 5290 5300 5310 5320cattaattgc gttgcgctca ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat5330 5340 5350 5360 5370 5380 5390cggccaacgc gcggtttgcg gcggaagcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg5400 5410 5420 5430 5440 5450 5460cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta tccacagaat5470 5480 5490 5500 5510 5520 5530caggggataa cgcaggaaag aacatgtgag caaaaggcca gcaaaaggcc aggaaccgta aaaaggccgc5540 5550 5560 5570 5580 5590 5600gttgctggcg tttttccata ggctccgccc ccctgacgag catcacaaaa atcgacgctc aagtcagagg5610 5620 5630 5640 5650 5660 5670tggcgaaacc cgacaggact ataaagatac caggcgtttc cccctggaag ctccctcgtg cgctctcctg5680 5690 5700 5710 5720 5730 5740ttccgaccct gccgcttacc ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcaatg5750 5760 5770 5780 5790 5800 5810ctcacgctgt aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc5820 5830 5840 5850 5860 5870 5880gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga cacgacttat5890 5900 5910 5920 5930 5940 5950cgccattggc agcagccact ggtaacagga ttagcagagc gaggtatgta ggcggtgcta cagagttctt5960 5970 5980 5990 6000 6010 6020gaagtggtgg cctaactacg gctacactag aaggacagta tttggtatct gcgctctgct gaagccagtt6030 6040 6050 6060 6070 6080 6090accttcggaa aaagagttgg tagctcttga tccggcaaac aaaccaccgc tggtagcggt ggtttttttg6100 6110 6120 6130 6140 6150 6160tttgcaagca gcagattacg cgcagaaaaa aaggatctca agaa6atcct ttgatctttt ctacggggtc6170 6180 6190 6200 6210 6220 6230tgacgctcag tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc6240 6250 6260 6270 6280 6290 6300tagatccttt taaaattaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact tggtctgaca6310 6320 6330 6340 6350 6360 6370gttaccaatg cttaatcagt gaggcaccta tctcagcgat ctgtctattt cgttcatcca tagttgcctg6380 6390 6400 6410 6420 6430 6440actccccgtc gtgtagataa ctacgatacg ggagggctta ccatctggcc ccagtgctgc aatgataccg6450 6460 6470 6480 6490 6500 6510cgagacccac gctcaccggc tccagattta tcagcaataa accagccagc cggaagggcc gagcgcagaa6520 6530 6540 6550 6560 6570 6580gtggtcctgc aactttatcc gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc6590 6600 6610 6620 6630 6640 6650gccagttaat agtttgcgca acgttgttgc cattgctaca ggcatcgtgg tgtcacgctc gtcgtttggt6660 6670 6680 6690 6700 6710 6720atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc ccccatgttg tgcaaaaaag6730 6740 6750 6760 6770 6780 6790cggttagctc cttcggtcct ccgatcgttg tcagaagtaa gttggccgca gtgttatcac tcatggttat6800 6810 6820 6830 6840 6850 6860ggcagcactg cataattctc ttactgtcat gccatccgta agatgctttt ctgtgactgg tgagtactca6870 6880 6890 6900 6910 6920 6930accaagtcat tctgagaata gtgtatgcgg cgaccgagtt gctcttgccc ggcgtcaata cgggataata6940 6950 6960 6970 6980 6990 7000ccgcgccaca tagcagaact ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag7010 7020 7030 7040 7050 7060 7070gatcttaccg ctgttgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc agcatctttt7080 7090 7100 7110 7120 7130 7140actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga ataagggcga7150 7160 7170 7180 7190 7200 7210cacggaaatg ttgaatactc atactcttcc tttttcaata ttattgaagc atttatcagg gttattgtct7220 7230 7240 7250 7260 7270 7280catgagcgga tacatatttg aatgtattta gaaaaataaa caaatagggg ttccgcgcac atttccccga7290aaagtgccac ctgacgtcseq : __________________________________________________________________________seq . id . no . 4phcv - 16210 20 30 40 50 60 70mlpglallll aawtaralev ptdgnaglla epqiamfcgr lnmhmnvqng kwdsdpsgtk tcidtkethv80 90 100 110 120 130 140tggsaghtta glvrllspga kqniqlintn gswhinstal ncneslntgw laglfyhhkf nssgcperla150 160 170 180 190 200 210scrrltdfaq gggpisyang sglderpycw hypprpcgiv paksvcgpvy cftpspvvvg ttdrsgapty220 230 240 250 260 270 280swgandtdvf vlnntrpplg nwfgctwmns tgftkvcgap pcviggvgnn tllcptdcfr khpeatysrc290 300 310 320 330 340 350gsgpwitprc mvdypyrlwh ypctinytif kvrmyvggve hrleaacnwt rgercdledr drselsplll360 370 380 390 400 410 420sttqwqvlpc sfttlpalst glihlhqniv dvqylygvgs siaswaikwe ydvllfllla darvcsclwm430 440 450 460 470 480 490mllisqaeaa leisevkmda efrhdsgyev hhqklvffae dvgsnkgaii glmvggvvia tvivitlvml500 510 520 530kkkqytsihh gvvevdaavt peerhlskmq qngyenptyk ffeqmqn . pep : __________________________________________________________________________seq . id . no . 5phcv . sub .-- 167circular sequence with junction at 710610 20 30 40 50 60 70gacggatcgg gagatctccc gatcccctat ggtcgactct cagtacaatc tgctctgatg ccgcatagtt80 90 100 110 120 130 140aagccagtat ctgctccctg cttgtgtgtt ggaggtcgct gagtagtgcg cgagcaaaat ttaagctaca150 160 170 180 190 200 210acaaggcaag gcttgaccga caattgcatg aagaatctgc ttagggttag gcgttttgcg ctgcttcgcg220 230 240 250 260 270 280atgtacgggc cagatatacg cgttgacatt gattattgac tagttattaa tagtaatcaa ttacgggqtq290 300 310 320 330 340 350attagttcat agcccatata tggagttccg cgttacataa cttacggtaa atggcccgcc tggctgaccg360 370 380 390 400 410 420cccaacgacc cccgcccatt gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc430 440 450 460 470 480 490attgacgtca atgggtggac tattttcggt aaactgccca cttggcagta catcaagtgt atcatatgcc500 510 520 530 540 550 560aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta570 580 590 600 610 620 630tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac catggtgatg cggttttggc640 650 660 670 680 690 700agtacatcaa tgggcgtgga tagcggtttg actcacgggg atttccaagt ctccacccca ttgacgtcaa710 720 730 740 750 760 770tgggagtttg ttttggcacc aaaatcaacg ggactttcca aaatgtcgta acaactccgc cccattgacg780 790 800 810 820 830 840caaatgggcg gtaggcgtgt acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca850 860 870 880 890 900 910ctgcttaact ggcttatcga aattaatacg actcactata gggagaccgg aagctttgct ctagactgga920 930 940 950 960 970 980attcgggcgc gatgctgccc ggtttggcac tgctcctgct ggccgcctgg acggctcggg cgctggaggt990 1000 1010 1020 1030 1040 1050acccactgat ggtaatgctg gcctgctggc tgaaccccag attgccatgt tctgtggcag actgaacatg1060 1070 1080 1090 1100 1110 1120cacatgaatg tccagaatgg gaagtgggat tcagatccat cagggaccaa aacctgcatt gataccaagg1130 1140 1150 1160 1170 1180 1190aaacccacgt caccggggga agtgccggcc acaccacggc tgggcttgtt cgtctccttt caccaggcgc1200 1210 1220 1230 1240 1250 1260caagcagaac atccaactga tcaacaccaa cggcagttgg cacatcaata gcacggcctt gaactgcaat1270 1280 1290 1300 1310 1320 1330gaaagcctta acaccggctg gttagcaggg ctcttctatc accacaaatt caactcttca ggttgtcctg1340 1350 1360 1370 1380 1390 1400agaggttggc cagctgccga cgccttaccg attttgccca gggcgggggt cctatcagtt acgccaacgg1410 1420 1430 1440 1450 1460 1470aagcggcctc gatgaacgcc cctactgctg gcactaccct ccaagacctt gtggcattgt gcccgcaaag1480 1490 1500 1510 1520 1530 1540agcgtgtgtg gcccggtata ttgcttcact cccagccccg tggtggtggg aacgaccgac aggtcgggcg1550 1560 1570 1580 1590 1600 1610cgcctaccta cagctggggt gcaaatgata cggatgtctt tgtccttaac aacaccaggc caccgctggg1620 1630 1640 1650 1660 1670 1680caattggttc ggttgcacct ggatgaactc aactggattc accaaagtgt gcggagcgcc cccttgtgtc1690 1700 1710 1720 1730 1740 1750atcggagggg tgggcaacaa caccttgctc tgccccactg attgcttccg caagcatccg gaagccacat1760 1770 1780 1790 1800 1810 1820actctcggtg cggctccggt ccctggatta cacccaggtg catggtcgac tacccgtata ggctttggca1830 1840 1850 1860 1870 1880 1890ctatccttgt accatcaatt acaccatatt caaagtcagg atgtacgtgg gaggggtcga gcacaggctg1900 1910 1920 1930 1940 1950 1960gaagcggcct gcaactggac gcggggcgaa cgctgtgatc tggaagacag ggacaggtcc gagctcagcc1970 1980 1990 2000 2010 2020 2030cgttactgct gtccaccacg cagtggcagg tccttccgtg ttctttcacg accctgccag cctagatctc2040 2050 2060 2070 2080 2090 2100tgaagtgaag atggatgcag aattccgaca tgactcagga tatgaagttc atcatcaaaa attggtgttc2110 2120 2130 2140 2150 2160 2170tttgcagaag atgtgggttc aaacaaaggt gcaatcattg gactcatggt gggcggtgtt gtcatagcga2180 2190 2200 2210 2220 2230 2240cagtgatcgt catcaccttg gtgatgctga agaagaaaca gtacacatcc attcatcatg gtgtggtgga2250 2260 2270 2280 2290 2300 2310ggttgacgcc gctgtcaccc cagaggagcg ccacctgtcc aagatgcagc agaacggcta cgaaaatcca2320 2330 2340 2350 2360 2370 2380acctacaagt tctttgagca gatgcagaac tagacccccg ccacagcagc ctctgaagtt ggacagcaaa2390 2400 2410 2420 2430 2440 2450accattgctt cactacccat cggtgtccat ttatagaata atgtgggaag aaacaaaccc gttttatgat2460 2470 2480 2490 2500 2510 2520ttactcatta tcgccttttg acagctgtgc tgtaacacaa gtagatgcct gaacttgaat taatccacac2530 2540 2550 2560 2570 2580 2590atcagtaatg tattctatct ctctttacat tttggtctct atactacatt attaatgggt tttgtgtact2600 2610 2620 2630 2640 2650 2660gtaaagaatt tagctgtatc aaactagtgc atgaataggc cgctcgagca tgcatctaga gggccctatt2670 2680 2690 2700 2710 2720 2730ctatagtgtc acctaaatgc tcgctgatca gcctcgactg tgccttctag ttgccagcca tctgttgttt2740 2750 2760 2770 2780 2790 2800gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc ctttcctaat aaaatgagga2810 2820 2830 2840 2850 2860 2870aattgcatcg cattgtctga gtaggtgtca ttctattctg gggggtgggg tggggcagga cagcaagggg2880 2890 2900 2910 2920 2930 2940gaggattggg aagacaatag caggcatgct ggggatgcgg tgggctctat ggaaccagct ggggctcgag2950 2960 2970 2980 2990 3000 3010gggggatccc cacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg cagcgtgacc3020 3030 3040 3050 3060 3070 3080gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc ctttctcgcc acgttcgccg3090 3100 3110 3120 3130 3140 3150gctttccccg tcaagctcta aatcggggca tccctttagg gttccgattt agtgctttac ggcacctcga3160 3170 3180 3190 3200 3210 3220ccccaaaaaa cttgattagg gtgatggttc acgtagtggg ccatcgccct gatagacggt ttttcgcctt3230 3240 3250 3260 3270 3280 3290tactgagcac tctttaatag tggactcttg ttccaaactg gaacaacact caaccctatc tcggtctatt3300 3310 3320 3330 3340 3350 3360cttttgattt ataagatttc catcgccatg taaaagtgtt acaattagca ttaaattact tctttatatg3370 3380 3390 3400 3410 3420 3430ctactattct tttggcttcg ttcacggggt gggtaccgag ctcgaattct gtggaatgtg tgtcagttag3440 3450 3460 3470 3480 3490 3500ggtgtggaaa gtccccaggc tccccaggca ggcagaagta tgcaaagcat gcatctcaat tagtcagcaa3510 3520 3530 3540 3550 3560 3570ccaggtgtgg aaagtcccca ggctccccag caggcagaag tatgcaaagc atgcatctca attagtcagc3580 3590 3600 3610 3620 3630 3640aaccatagtc ccgcccctaa ctccgcccat cccgccccta actccgccca gttccgccca ttctccgccc3650 3660 3670 3680 3690 3700 3710catggctgac taattttttt tatttatgca gaggccgagg ccgcctcggc ctctgagcta ttccagaagt3720 3730 3740 3750 3760 3770 3780agtgaggagg cttttttgga ggcctaggct tttgcaaaaa gctcccggga gcttggatat ccattttcgg3790 3800 3810 3820 3830 3840 3850atctgatcaa gagacaggat gaggatcgtt tcgcatgatt gaacaagatg gattgcacgc aggttctccg3860 3870 3880 3890 3900 3910 3920gccgcttggg tggagaggct attcggctat gactgggcac aacagacaat cggctgctct gatgccgccg3930 3940 3950 3960 3970 3980 3990tgttccggct gtcagcgcag gggcgcccgg ttctttttgt caagaccgac ctgtccggtg ccctgaatga4000 4010 4020 4030 4040 4050 4060actgcaggac gaggcagcgc ggctatcgtg gctggccacg acgggcgttc cttgcgcagc tgtgctcgac4070 4080 4090 4100 4110 4120 4130gttgtcactg aagcgggaag ggactggctg ctattgggcg aagtgccggg gcaggatctc ctgtcatctc4140 4150 4160 4170 4180 4190 4200accttgctcc tgccgagaaa gtatccatca tggctgatgc aatgcggcgg ctgcatacgc ttgatccggc4210 4220 4230 4240 4250 4260 4270tacctgccca ttcgaccacc aagcgaaaca tcgcatcgag cgagcacgta ctcggatgga agccggtctt4280 4290 4300 4310 4320 4330 4340gtcgatcagg atgatctgga cgaagagcat caggggctcg cgccagccga actgttcgcc aggctcaagg4350 4360 4370 4380 4390 4400 4410cgcgcatgcc cgacggcgag gatctcgtcg tgacccatgg cgatgcctgc ttgccgaata tcatggtgga4420 4430 4440 4450 4460 4470 4480aaatggccgc ttttctggat tcatcgactg tggccggctg ggtgtggcgg accgctatca ggacatagcg4490 4500 4510 4520 4530 4540 4550ttggctaccc gtgatattgc tgaagagctt ggcggcgaat gggctgaccg cttcctcgtg ctttacggta4560 4570 4580 4590 4600 4610 4620tcgccgctcc cgattcgcag cgcatcgcct tctatcgcct tcttgacgag ttcttctgag cgggactctg4630 4640 4650 4660 4670 4680 4690gggttcgaaa tgaccgacca agcgacgccc aacctgccat cacgagattt cgattccacc gccgccttct4700 4710 4720 4730 4740 4750 4760atgaaaggtt gggcttcgga atcgttttcc gggacgccgg ctggatgatc ctccagcgcg gggatctcat4770 4780 4790 4800 4810 4820 4830gctggagttc ttcgcccacc ccaacttgtt tattgcagct tataatggtt acaaataaag caatagcatc4840 4850 4860 4870 4880 4890 4900acaaatttca caaataaagc atttttttca ctgcattcta gttgtggttt gtccaaactc atcaatgtat4910 4920 4930 4940 4950 4960 4970cttatcatgt ctggatcccg tcgacctcga gagcttggcg taatcatggt catagctgtt tcctgtgtga4980 4990 5000 5010 5020 5030 5040aattgttatc cgctcacaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc tggggtgcct5050 5060 5070 5080 5090 5100 5110attgagtgag ctaactcaca ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa acctgtcgtg5120 5130 5140 5150 5160 5170 5180ccagctgcat taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc5190 5200 5210 5220 5230 5240 5250tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc gagcggtatc agctcactca aaggcggtaa5260 5270 5280 5290 5300 5310 5320tacggttatc cacagaatca ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag5330 5340 5350 5360 5370 5380 5390gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat5400 5410 5420 5430 5440 5450 5460cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc cctggaagct5470 5480 5490 5500 5510 5520 5530ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc cttcgggaag5540 5550 5560 5570 5580 5590 5600cgtggcgctt tctcaatgct cacgctgtag gtatctcagt tcggtgtagg tcgttcgctc caagctgggc5610 5620 5630 5640 5650 5660 5670tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc5680 5690 5700 5710 5720 5730 5740cggtaagaca cgacttatcg ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg5750 5760 5770 5780 5790 5800 5810cggtgctaca gagttcttga agtggtggcc taactacggc tacactagaa ggacagtatt tggtatctgc5820 5830 5840 5850 5860 5870 5880gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa accaccgptg5890 5900 5910 5920 5930 5940 5950gtagcggtgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa ggatctcaag aagatccttt5960 5970 5980 5990 6000 6010 6020gatcttttct acggggtctg acgctcagtg gaacgaaaac tcacgttaag ggattttggt catgagatta6030 6040 6050 6060 6070 6080 6090tcaaaaagga tcttcaccta gatcctttta aattaaaaat gaagttttaa atcaatctaa agtatatatg6100 6110 6120 6130 6140 6150 6160agtaaacttg gtctgacaat taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg6170 6180 6190 6200 6210 6220 6230ttcatccata gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc atctggcccc6240 6250 6260 6270 6280 6290 6300agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc agcaataaac cagccagccg6310 6320 6330 6340 6350 6360 6370gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag tctattaatt gttgccggga6380 6390 6400 6410 6420 6430 6440agctagagta agtagttcgc cagttaatag tttgcgcaac gttgttgcca ttgctacagg catcgtggtg6450 6460 6470 6480 6490 6500 6510tcacgctcgt cgtttggtat ggcttcattc agctccggtt cccaacgatc aaggcgagtt acatgatccc6520 6530 6540 6550 6560 6570 6580ccatgttgtg caaaaaagcg gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt6590 6600 6610 6620 6630 6640 6650gttatcactc atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag atgcttttct6660 6670 6680 6690 6700 6710 6720gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg accgagttgc tcttgcccgg6730 6740 6750 6760 6770 6780 6790cgtcaatacg ggataatacc gcgccacata gcagaacttt aaaagtgctc atcattggaa aacgttcttc6800 6810 6820 6830 6840 6850 6860ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc agttcgatgt aacccactcg tgcacccaac6870 6880 6890 6900 6910 6920 6930tgatcttcag catcttttac tttcaccagc gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa6940 6950 6960 6970 6980 6990 7000aaaagggaat aagggcgaca cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat7010 7020 7030 7040 7050 7060 7070ttatcagggt tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca aataggggtt7080 7090 7100ccgcgcacat ttccccgaaa agtgccacct gacgtcseq : __________________________________________________________________________seq . id . no . 6phcv - 16710 20 30 40 50 60 70mlpglallll aawtaralev ptdgnaglla epqiamfcgr lnmhmnvqng kwdsdpsgtk tcidtkethv80 90 100 110 120 130 140tggsaghtta glvrllspga kqniqlintn gswhinstal ncneslntgw laglfyhhkf nssgcperla150 160 170 180 190 200 210scrrltdfaq gggpisyang sglderpycw hypprpcgiv paksvcgpvy cftpspvvvg ttdrsgapty220 230 240 250 260 270 280swgandtdvf vlnntrpplg nwfgctwmns tgftkvcgap pcviggvgnn tllcptdcfr khpeatysrc290 300 310 320 330 340 350gsgpwitprc mvdypyrlwh ypctinytif kvrmyvggve hrleaacnwt rgercdledr drselsplll360sttqwqvlpc sfttlpa . pep : __________________________________________________________________________seq . id . no . 7phcv . sub .-- 168circular sequence with junction at 481010 20 30 40 50 60 70gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt tgtttgccgg atcaagagct80 90 100 110 120 130 140accaactctt tttccgaagg taactggctt cagcagagcg cagataccaa atactgtcct tctagtgtag150 160 170 180 190 200 210ccgtagttag gccaccactt caagaactct gtagcaccgc ctacatacct cgctctgcta atcctgttac220 230 240 250 260 270 280cagtggctgc tgccagtggc gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa290 300 310 320 330 340 350ggcgcagcgg tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa360 370 380 390 400 410 420ctgagatacc tacagcgtga gcattgagaa agcgccacgc ttcccgaagg gagaaaggcg gacaggtatc430 440 450 460 470 480 490cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg ggaaacgcct ggtatcttta500 510 520 530 540 550 560tagtcctgtc gggtttcgcc acctctgact tgagcgtcga tttttgtgat gctcgtcagg ggggcggagc570 580 590 600 610 620 630ctatggaaaa acgccagcaa cgcaagctag cttctagcta gaaattgtaa acgttaatat tttgttaaaa640 650 660 670 680 690 700ttcgcgttaa atttttgtta aatcagctca ttttttaacc aataggccga aatcggcaaa atcccttata710 720 730 740 750 760 770aatcaaaaga atagcccgag atagggttga gtgttgttcc agtttggaac aagagtccac tattaaagaa780 790 800 810 820 830 840cgtggactcc aacgtcaaag ggcgaaaaac cgtctatcag ggcgatggcc gcccactacg tgaaccatca850 860 870 880 890 900 910cccaaatcaa gttttttggg gtcgaggtgc cgtaaagcac taaatcggaa ccctaaaggg agcccccgat920 930 940 950 960 970 980ttagagcttg acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggcgc990 1000 1010 1020 1030 1040 1050tagggcgctg gcaagtgtag cggtcacgct gcgcgtaacc accacacccg ccgcgcttaa tgcgccgcta1060 1070 1080 1090 1100 1110 1120cagggcgcgt actatggttg ctttgacgag accgtataac gtgctttcct cgttggaatc agagcgggag1130 1140 1150 1160 1170 1180 1190ctaaacagga ggccgattaa agggatttta gacaggaacg gtacgccagc tggatcaccg cggtctttct1200 1210 1220 1230 1240 1250 1260caacgtaaca ctttacagcg gcgcgtcatt tgatatgatg cgccccgctt cccgataagg gagcaggcca1270 1280 1290 1300 1310 1320 1330gtaaaagcat tacccgtggt ggggttcccg agcggccaaa gggagcagac tctaaatctg ccgtcatcga1340 1350 1360 1370 1380 1390 1400cttcgaaggt tcgaatcctt cccccaccac catcactttc aaaagtccga aagaatctgc tccctgcttg1410 1420 1430 1440 1450 1460 1470tgtgttggag gtcgctgagt agtgcgcgag taaaatttaa gctacaacaa ggcaaggctt gaccgacaat1480 1490 1500 1510 1520 1530 1540tgcatgaaga atctgcttag ggttaggcgt tttgcgctgc ttcgcgatgt acgggccaga tatacgcgtt1550 1560 1570 1580 1590 1600 1610gacattgatt attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga1620 1630 1640 1650 1660 1670 1680gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg cccattgacg1690 1700 1710 1720 1730 1740 1750tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg acgtcaatgg gtggactatt1760 1770 1780 1790 1800 1810 1820tacggtaaac tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa1830 1840 1850 1860 1870 1880 1890tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac1900 1910 1920 1930 1940 1950 1960atctacgtat tagtcatcgt tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc1970 1980 1990 2000 2010 2020 2030ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa2040 2050 2060 2070 2080 2090 2100tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg2110 2120 2130 2140 2150 2160 2170tgggaggtct atataagcag agctctctgg ctaactagag aacccactgc ttaactggct tatcgaaatt2180 2190 2200 2210 2220 2230 2240aatacgactc actataggga gaccggaagc ttggtaccga gctcggatct gccaccatgg caacaggatc2250 2260 2270 2280 2290 2300 2310aagaacatca ctgctgctgg catttggact gctgtgtctg ccatggctgc aagaaggatc agcagcagca2320 2330 2340 2350 2360 2370 2380gcagcgaatt cggatcccta ccaagtgcgc aattcctcgg ggctttacca tgtcaccaat gattgcccta2390 2400 2410 2420 2430 2440 2450attcgagtat tgtgtacgag gcggccgatg ccatcctaca cactccgggg tgtgtccctt gcgttcgcga2460 2470 2480 2490 2500 2510 2520gggtaacgcc tcgaggtgtt gggtggcggt gacccccacg gtggccacca gggacggtaa actccccaca2530 2540 2550 2560 2570 2580 2590acgcagcttc gacgtcatat cgatctgctc gtcgggagcg ccaccctctg ctcggccctc tacgtggggg2600 2610 2620 2630 2640 2650 2660acctgtgcgg gtctgtcttt cttgttggtc aactgtttac cttctctccc aggcgccact ggacgacgca2670 2680 2690 2700 2710 2720 2730agactgcaat tgttctatct atcccggcca tataacgggt catcgtatgg catgggatat gatgatgaac2740 2750 2760 2770 2780 2790 2800tggtccccta cggcagcgtt ggtggtagct cagctgctcc ggatcccaca agccatcttg gacatgatcg2810 2820 2830 2840 2850 2860 2870ctggtgccca ctggggagtc ctggcgggca tagcgtattt ctccatggtg gggaactggg cgaaggtcct2880 2890 2900 2910 2920 2930 2940ggtagtgctg ctgctatttg ccggcgttga cgcggagatc taatctagag ggccctattc tatagtgtca2950 2960 2970 2980 2990 3000 3010cctaaatgct agaggatctt tgtgaaggaa ccttacttct gtggtgtgac ataattggac aaactaccta3020 3030 3040 3050 3060 3070 3080cagagattta aagctctaag gtaaatataa aatttttaag tgtataatgt gttaaactac tgattctaat3090 3100 3110 3120 3130 3140 3150tgtttgtgta ttttagattc caacctatgg aactgatgaa tgggagcagt ggtggaatgc ctttaatgag3160 3170 3180 3190 3200 3210 3220gaaaacctgt tttgctcaga agaaatgcca tctagtgatg atgaggctac tgctgactct caacattcta3230 3240 3250 3260 3270 3280 3290ctcctccaaa aaagaagaga aaggtagaag accccaagga ctttccttca gaattgctaa gttttttgag3300 3310 3320 3330 3340 3350 3360tcatgctgtg tttagtaata gaactcttgc ttgctttgct atttacacca caaaggaaaa agctgcactg3370 3380 3390 3400 3410 3420 3430ctatacaaga aaattatgga aaaatattct gtaaccttta taagtaggca taacagttat aatcataaca3440 3450 3460 3470 3480 3490 3500tactgttttt tcttactcca cacaggcata gagtgtctgc tattaataac tatgctcaaa aattgtgtac3510 3520 3530 3540 3550 3560 3570ctttagcttt ttaatttgta aaggggttaa taaggaatat ttgatgtata gtgccttgac tagagatcat3580 3590 3600 3610 3620 3630 3640aatcagccat accacatttg tagaggtttt acttgcttta aaaaacctcc cacacctccc cctgaacctg3650 3660 3670 3680 3690 3700 3710aaacataaaa tgaatgcaat tgttgttgtt aacttgttta ttgcagctta taatggttac aaataaagca3720 3730 3740 3750 3760 3770 3780atagcatcac aaatttcaca aataaagcat ttttttcact gcattctagt tgtggtttgt ccaaactcat3790 3800 3810 3820 3830 3840 3850caatgtatct tatcatgtct ggatcgatcc cgccatggta tcaacgccat atttctattt acagtaggga3860 3870 3880 3890 3900 3910 3920cctcttcgtt gtgtaggtac cgctgtattc ctagggaaat agtagaggca ccttgaactg tctgcatcag3930 3940 3950 3960 3970 3980 3990ccatatagcc cccgctgttc gacttacaaa cacaggcaca gtactgacaa acccatacac ctcctctgaa4000 4010 4020 4030 4040 4050 4060atacccatag ttgctagggc tgtctccgaa ctcattacac cctccaaagt cagagctgta atttcgccat4070 4080 4090 4100 4110 4120 4130caagggcagc gagggcttct ccagataaaa tagcttctgc cgagagtccc gtaagggtag acacttcagc4140 4150 4160 4170 4180 4190 4200taatccctcg atgaggtcta ctagaatagt cagtgcggct cccattttga aaattcactt acttgatcag4210 4220 4230 4240 4250 4260 4270cttcagaaga tggcggaggg cctccaacac agtaattttc ctcccgactc ttaaaataga aaatgtcaag4280 4290 4300 4310 4320 4330 4340tcagttaagc aggaagtgga ctaactgacg cagctggccg tgcgacatcc tcttttaatt agttgctagg4350 4360 4370 4380 4390 4400 4410caacgccctc cagagggcgt gtggttttgc aagaggaagc aaaagcctct ccacccaggc ctagaatgtt4420 4430 4440 4450 4460 4470 4480tccacccaat cattactatg acaacagctg ttttttttag tattaagcag aggccgggga cccctggccc4490 4500 4510 4520 4530 4540 4550gcttactctg gagaaaaaga agagaggcat tgtagaggct tccagaggca acttgtcaaa acaggactgc4560 4570 4580 4590 4600 4610 4620ttctatttct gtcacactgt ctggccctgt cacaaggtcc agcacctcca tacccccttt aataagcagt4630 4640 4650 4660 4670 4680 4690ttgggaacgg gtgcgggtct tactccgccc atcccgcccc taactccgcc cagttccgcc cattctccgc4700 4710 4720 4730 4740 4750 4760cccatggctg actaattttt tttatttatg cagaggccga ggccgcctcg gcctctgagc tattccagaa4770 4780 4790 4800 4810gtagtgagga ggcttttttg gaggcctagg cttttgcaaa aagctaattcseq : __________________________________________________________________________seq . id . no . 8phcv - 16810 20 30 40 50 60 70matgsrtsll lafgllclpw lqegsaaaaa nsdpyqvrns sglyhvtndc pnssivyeaa dailhtpgcv80 90 100 110 120 130 140pcvregnasr cwvavtptva trdgklpttq lrrhidllvg satlcsalyv gdlcgsvflv gqlftfsprr150 160 170 180 190 200 210hwttqdcncs iypghitghr mawdmmmnws ptaalvvaql lripqaildm iagahwgvla giayfsmvgn220wakvlvvlll fagvdaei . pep : __________________________________________________________________________seq . id . no . 9phcv . sub .-- 169circular sequence with junction at 532310 20 30 40 50 60 70gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt tgtttgccgg atcaagagct80 90 100 110 120 130 140accaactctt tttccgaagg taactggctt cagcagagcg cagataccaa atactgtcct tctagtgtag150 160 170 180 190 200 210ccgtagttag gccaccactt caagaactct gtagcaccgc ctacatacct cgctctgcta atcctgttac220 230 240 250 260 270 280cagtggctgc tgccagtggc gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa290 300 310 320 330 340 350ggcgcagcgg tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa360 370 380 390 400 410 420ctgagatacc tacagcgtga gcattgagaa agcgccacgc ttcccgaagg gagaaaggcg gacaggtatc430 440 450 460 470 480 490cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg ggaaacgcct ggtatcttta500 510 520 530 540 550 560tagtcctgtc gggtttcgcc acctctgact tgagcgtcga tttttgtgat gctcgtcagg ggggcggagc570 580 590 600 610 620 630ctatggaaaa acgccagcpa cgcaagctag cttctagcta gaaattgtaa acgttaatat tttgttaaaa640 650 660 670 680 690 700ttcgcgttaa atttttgtta aatcagctca ttttttaacc aataggccga aatcggcaaa atcccttata710 720 730 740 750 760 770aatcaaaaga atagcccgag atagggttga gtgttgttcc agtttggaac aagagtccac tattaaagaa780 790 800 810 820 830 840cgtggactcc aacgtcaaag ggcgaaaaac cgtctatcag ggcgatggcc gcccactacg tgaaccatca850 860 870 880 890 900 910cccaaatcaa gttttttggg gtcgaggtgc cgtaaagcac taaatcggaa ccctaaaggg agcccccgat920 930 940 950 960 970 980ttagagcttg acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggcgc990 1000 1010 1020 1030 1040 1050tagggcgctg gcaagtgtag cggtcacgct gcgcgtaacc accacacccg ccgcgcttaa tgcgccgcta1060 1070 1080 1090 1100 1110 1120cagggcgcgt actatggttg ctttgacgag accgtataac gtgctttcct cgttggaatc agagcgggag1130 1140 1150 1160 1170 1180 1190ctaaacagga ggccgattaa agggatttta gacaggaacg gtacgccagc tggatcaccg cggtctttct1200 1210 1220 1230 1240 1250 1260caacgtaaca ctttacagcg gcgcgtcatt tgatatgatg cgccccgctt cccgataagg gagcaggcca1270 1280 1290 1300 1310 1320 1330gtaaaagcat tacccgtggt ggggttcccg agcggccaaa gggagcagac tctaaatctg ccgtcatcga1340 1350 1360 1370 1380 1390 1400cttcgaaggt tcgaatcctt cccccaccac catcactttc aaaagtccga aagaatctgc tccctgcttg1410 1420 1430 1440 1450 1460 1470tgtgttggag gtcgctgagt agtgcgcgag taaaatttaa gctacaacaa ggcaaggctt gaccgacaat1480 1490 1500 1510 1520 1530 1540tgcatgaaga atctgcttag ggttaggcgt tttgcgctgc ttcgcgatgt acgggccaga tatacgcgtt1550 1560 1570 1580 1590 1600 1610gacattgatt attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga1620 1630 1640 1650 1660 1670 1680gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg cccattgacg1690 1700 1710 1720 1730 1740 1750tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg acgtcaatgg gtggactatt1760 1770 1780 1790 1800 1810 1820tacggtaaac tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa1830 1840 1850 1860 1870 1880 1890tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac1900 1910 1920 1930 1940 1950 1960atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc1970 1980 1990 2000 2010 2020 2030ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa2040 2050 2060 2070 2080 2090 2100tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg2110 2120 2130 2140 2150 2160 2170tgggaggtct atataagcag agctctctgg ctaactagag aacccactgc ttaactggct tatcgaaatt2180 2190 2200 2210 2220 2230 2240aatacgactc actataggga gaccggaagc ttggtaccga gctcggatct gccaccatgg caacaggatc2250 2260 2270 2280 2290 2300 2310aagaacatca ctgctgctgg catttggact gctgtgtctg ccatggctgc aagaaggatc agcagcagca2320 2330 2340 2350 2360 2370 2380gcagcgaatt cagaaaccca cgtcaccggg ggaagtgccg gccacaccac ggctgggctt gttcgtctcc2390 2400 2410 2420 2430 2440 2450tttcaccagg cgccaagcag aacatccaac tgatcaacac caacggcagt tggcacatca atagcacggc2460 2470 2480 2490 2500 2510 2520cttgaactgc aatgaaagcc ttaacaccgg ctggttagca gggctcttct atcaccacaa attcaactct2530 2540 2550 2560 2570 2580 2590tcaggttgtc ctgagaggtt ggccagctgc cgacgcctta ccgat ttt gc ccagggcggg ggtcctatca2600 2610 2620 2630 2640 2650 2660gttacgccaa cggaagcggc ctcgatgaac gcccctactg ctggcactac cctccaagac cttgtggcat2670 2680 2690 2700 2710 2720 2730tgtgcccgca aagagcgtgt gtggcccggt atattgcttc actcccagcc ccgtggtggt gggaacgacc2740 2750 2760 2770 2780 2790 2800gacaggtcgg gcgcgcctac ctacagctgg ggtgcaaatg atacggatgt ctttgtcctt aacaacacca2810 2820 2830 2840 2850 2860 2870ggccaccgct gggcaattgg ttcggttgca cctggatgaa ctcaactgga ttcaccaaag tgtgcggagc2880 2890 2900 2910 2920 2930 2940gcccccttgt gtcatcggag gggtgggcaa caacaccttg ctctgcccca ctgattgttt ccgcaagcat2950 2960 2970 2980 2990 3000 3010ccggaagcca catactctcg gtgcggctcc ggtccctgga ttacacccag gtgcatggtc gactacccgt3020 3030 3040 3050 3060 3070 3080ataggctttg gcactatcct tgtaccatca attacaccat attcaaagtc aggatgtacg tgggaggggt3090 3100 3110 3120 3130 3140 3150cgagcacagg ctggaagcgg cctgcaactg gacgcggggc gaacgctgtg atctggaaga cagggacagg3160 3170 3180 3190 3200 3210 3220tccgagctca gcccgttact gctgtccacc acgcagtggc aggtccttcc gtgttctttc acgaccctgc3230 3240 3250 3260 3270 3280 3290cagccttgtc caccggcctc atccacctcc accagaacat tgtggacgtg cagtacttgt acggggtagg3300 3310 3320 3330 3340 3350 3360gtcaagcatc gcgtcctggg ctattaagtg ggagtacgac gttctcctgt tccttctgct tgcagacgcg3370 3380 3390 3400 3410 3420 3430cgcgtttgct cctgcttgtg gatgatgtta ctcatatccc aagcggaggc ggctttggag aactaatcta3440 3450 3460 3470 3480 3490 3500gagggcccta ttctatagtg tcacctaaat gctagaggat ctttgtgaag gaaccttact tctgtggtgt3510 3520 3530 3540 3550 3560 3570gacataattg gacaaactac ctacagagat ttaaagctct aaggtaaata taaaattttt aagtgtataa3580 3590 3600 3610 3620 3630 3640tgtgttaaac tactgattct aattgtttgt gtattttaga ttccaaccta tggaactgat gaatgggagc3650 3660 3670 3680 3690 3700 3710agtggtggaa tgcctttaat gaggaaaacc tgttttgctc agaagaaatg ccatctagtg atgatgaggc3720 3730 3740 3750 3760 3770 3780tactgctgac tctcaacatt ctactcctcc aaaaaagaag agaaaggtag aagaccccaa ggactttcct3790 3800 3810 3820 3830 3840 3850tcagaattgc taagtttttt gagtcatgct gtgtttagta atagaactct tgcttgcttt gctatttaca3860 3870 3880 3890 3900 3910 3920ccacaaagga aaaagctgca ctgctataca agaaaattat ggaaaaatat tctgtaacct ttataagtag3930 3940 3950 3960 3970 3980 3990gcataacagt tataatcata acatactgtt ttttcttact ccacacaggc atagagtgtc tgctattaat4000 4010 4020 4030 4040 4050 4060aactatgctc aaaaattgtg taccttt agc tttttaattt gtaaaggggt taataaggaa tatttgatgt4070 4080 4090 4100 4110 4120 4130atagtgcctt gactagagat cataatcagc cataccacat ttgtagaggt tttacttgct ttaaaaaacc4140 4150 4160 4170 4180 4190 4200tcccacacct ccccctgaac ctgaaacata aaatgaatgc aattgttgtt gttaacttgt ttattgcagc4210 4220 4230 4240 4250 4260 4270ttataatggt tacaaataaa gcaatagcat cacaaatttc acaaataaag catttttttc actgcattct4280 4290 4300 4310 4320 4330 4340agttgtggtt tgtccaaact catcaatgta tcttatcatg tctggatcga tcccgccatig gtatcaacgc4350 4360 4370 4380 4390 4400 4410catatttcta tttacagtag ggacctcttc gttgtgtagg taccgctgta ttcctaggga aatagtagag4420 4430 4440 4450 4460 4470 4480gcaccttgaa ctgtctgcat cagcatata gcccccgctg ttcgacttac aaacacaggc acagtactga4490 4500 4510 4520 4530 4540 4550caaacccata cacctcctct gaaataccca tagttgctag ggctgtctcc gaactcatta caccctccaa4560 4570 4580 4590 4600 4610 4620agtcagagct gtaatttcgc catcaagggc agcgagggct tctccagata aaatagcttc tgccgagagt4630 4640 4650 4660 4670 4680 4690cccgtaaggg tagacacttc agctaatccc tcgatgaggt ctactagaat agtcagtgcg gctcccattt4700 4710 4720 4730 4740 4750 4760tgaaaattca cttacttgat cagcttcaga agatggcgga gggcctccaa cacagtaatt ttcctcccga4770 4780 4790 4800 4810 4820 4830ctcttaaaat agaaaatgtc aagtcagtta agcaggaagt ggactaactg acgcagctgg ccgtgcgaca4840 4850 4860 4870 4880 4890 4900tcctctttta attagttgct aggcaacgcc ctccagaggg cgtgtggttt tgcaagagga agcaaaagcc4910 4920 4930 4940 4950 4960 4970tctccaccca ggcctagaat gtttccaccc aatcattact atgacaacag ctgttttttt tagtattaag4980 4990 5000 5010 5020 5030 5040cagaggccgg ggacccctgg cccgcttact ctggagaaaa agaagagagg cattgtagag gcttccagag5050 5060 5070 5080 5090 5100 5110gcaacttgtc aaaacaggac tgcttctatt tctgtcacac tgtctggccc tgtcacaagg tccagcacct5120 5130 5140 5150 5160 5170 5180ccataccccc tttaataagc agtttgggaa cgggtgcggg tcttactccg cccatcccgc ccctaactcc5190 5200 5210 5220 5230 5240 5250gcccagttcc gcccattctc cgccccatgg ctgactaatt ttttttattt atgcagaggc cgaggccgcc5260 5270 5280 5290 5300 5310 5320tcggcctctg agctattcca gaagtagtga ggaggctttt ttggaggcct aggcttttgc aaaaagctaatccseq : __________________________________________________________________________seq . id . no . 10phcv - 16910 20 30 40 50 60 70matgsrtsll lafgllclpw lqegsaaaaa nsethvtggs aghttaglvr llspgakqni qlintngswh80 90 100 110 120 130 140instalncne slntgwlagl fyhhkfnssg cperlascrr ltdfaqgggp isyangsgld erpycwhypp150 160 170 180 190 200 210rpcgivpaks vcgpvycftp spvvvgttdr sgaptyswga ndtdvfvlnn trppignwfg ctwmnstgft220 230 240 250 260 270 280kvcgappcvi ggvgnutllc ptdcfrkhpe atysrcgsgp witprcmvdy pyrlwhypct ntytifkvrm290 300 310 320 330 340 350yvggvehrle aacnwtrger cdledrdrse lsplllsttq wqvlpcsftt lpalstglih lhqnivdvqy360 370 380 390 400lygvgssias waikweydvl lfllladarv csclwmmlli sqaeaalen . pep : __________________________________________________________________________seq . id . no . 11phcv . sub .-- 170circular sequence with junction at 512510 20 30 40 50 60 70gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt tgtttgccgg atcaagagct80 90 100 110 120 130 140accaactctt tttccgaagg taactggctt cagcagagcg cagataccaa atactgtcct tctagtgtag150 160 170 180 190 200 210ccgtagttag gccaccactt caagaactct gtagcaccgc ctacatacct cgctctgcta atcctgttac220 230 240 250 260 270 280cagtggctgc tgccagtggc gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa290 300 310 320 330 340 350ggcgcagcgg tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa360 370 380 390 400 410 420ctgagatacc tacagcgtga gcattgagaa agcgccacgc ttcccgaagg gagaaaggcg gacaggtatc430 440 450 460 470 480 490cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg ggaaacgcct ggtatcttta500 510 520 530 540 550 560tagtcctgtc gggtttcgcc acctctgact tgagcgtcga tttttgtgat gctcgtcagg ggggcggagc570 580 590 600 610 620 630ctatggaaaa acgccagcaa cgcaagctag cttctagcta gaaattgtaa acgttaatat tttgttaaaa640 650 660 670 680 690 700ttcgcgttaa atttttgtta aatcagctca ttttttaacc aataggccga aatcggcaaa atcccttata710 720 730 740 750 760 770aatcaaaaga atagcccgag atagggttga gtgttgttcc agtttggaac aagagtccac tattaaagaa780 790 800 810 820 830 840cgtggactcc aacgtcaaag ggcgaaaaac cgtctatcag ggcgatggcc gcccactacg tgaaccatca850 860 870 880 890 900 910cccaaatcaa gttttttggg gtcgaggtgc cgtaaagcac taaatcggaa ccctaaaggg agcccccgat920 930 940 950 960 970 980ttagagcttg acggggaaag ccggcgaacg tggcgagaaa ggaagggaag aaagcgaaag gagcgggcgc990 1000 1010 1020 1030 1040 1050tagggcgctg gcaagtgtag cggtcacgct gcgcgtaacc accacacccg ccgcgcttaa tgcgccgcta1060 1070 1080 1090 1100 1110 1120cagggcgcgt actatggttg ctttgacgag accgtataac gtgctttcct cgttggaatc agagcgggag1130 1140 1150 1160 1170 1180 1190ctaaacagga ggccgattaa agggatttta gacaggaacg gtacgccagc tggatcaccg cggtctttct1200 1210 1220 1230 1240 1250 1260caacgtaaca ctttacagcg gcgcgtcatt tgatatgatg cgccccgctt cccgataagg gagcaggcca1270 1280 1290 1300 1310 1320 1330gtaaaagcat tacccgtggt ggggttcccg agcggccaaa gggagcagac tctaaatctg ccgtcatcga1340 1350 1360 1370 1380 1390 1400cttcgaaggt tcgaatcctt cccccaccac catcactttc aaaagtccga aagaatctgc tccctgcttg1410 1420 1430 1440 1450 1460 1470tgtgttggag gtcgctgagt agtgcgcgag taaaatttaa gctacaacaa ggcaaggctt gaccgacaat1480 1490 1500 1510 1520 1530 1540tgcatgaaga atctgcttag ggttaggcgt tttgcgctgc ttcgcgatgt acgggccaga tatacgcgtt1550 1560 1570 1580 1590 1600 1610gacattgatt attgactagt tattaatagt aatcaattac ggggtcatta gttcatagcc catatatgga1620 1630 1640 1650 1660 1670 1680gttccgcgtt acataactta cggtaaatgg cccgcctggc tgaccgccca acgacccccg cccattgacg1690 1700 1710 1720 1730 1740 1750tcaataatga cgtatgttcc catagtaacg ccaataggga ctttccattg acgtcaatgg gtggactatt1760 1770 1780 1790 1800 1810 1820tacggtaaac tgcccacttg gcagtacatc aagtgtatca tatgccaagt acgcccccta ttgacgtcaa1830 1840 1850 1860 1870 1880 1890tgacggtaaa tggcccgcct ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac1900 1910 1920 1930 1940 1950 1960atctacgtat tagtcatcgc tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc1970 1980 1990 2000 2010 2020 2030ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt ggcaccaaaa2040 2050 2060 2070 2080 2090 2100tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa tgggcggtag gcgtgtacgg2110 2120 2130 2140 2150 2160 2170tgggaggtct atataagcag agctctctgg ctaactagag aacccactgc ttaactggct tatcgaaatt2180 2190 2200 2210 2220 2230 2240aatacgactc actataggga gaccggaagc ttggtaccga gctcggatct gccaccatgg caacaggatc2250 2260 2270 2280 2290 2300 2310aagaacatca ctgctgctgg catttggact gctgtgtctg ccatggctgc aagaaggatc agcagcagca2320 2330 2340 2350 2360 2370 2380gcagcgaatt cagaaaccca cgtcaccggg ggaagtgccg gccacaccac ggctgggctt gttcgtctcc2390 2400 2410 2420 2430 2440 2450tttcaccagg cgccaagcag aacatccaac tgatcaacac caacggcagt tggcacatca atagcacggc2460 2470 2480 2490 2500 2510 2520cttgaactgc aatgaaagcc ttaacaccgg ctggttagca gggctcttct atcaccacaa attcaactct2530 2540 2550 2560 2570 2580 2590tcaggttgtc ctgagaggtt ggccagctgc cgacgcctta ccgattttgc ccagggcggg ggtcctatca2600 2610 2620 2630 2640 2650 2660gttacgccaa cggaagcggc ctcgatgaac gcccctactg ctggcactac cctccaagac cttgtggcat2670 2680 2690 2700 2710 2720 2730tgtgcccgca aagagcgtgt gtggcccggt atattgcttc actcccagcc ccgtggtggt gggaacgacc2740 2750 2760 2770 2780 2790 2800gacaggtcgg gcgcgcctac ctacagctgg gctgcaaatg atacggatgt ctttgtcctt aacaacacca2810 2820 2830 2840 2850 2860 2870ggccaccgct gggcaattgg ttcggttgca cctggatgaa ctcaactgga ttcaccaaag tgtgcggagc2880 2890 2900 2910 2920 2930 2940gcccccttgt gtcatcggag gggtgggcaa caacaccttg ctctgcccca ctgattgctt ccgcaagcat2950 2960 2970 2980 2990 3000 3010ccggaagcca catactctcg gtgcggctcc ggtccctgga ttacacccag gtgcatggtc gactacccgt3020 3030 3040 3050 3060 3070 3080ataggctttg gcactatcct tgtaccatca attacaccat attcaaagtc aggatgtacg tgggaggggt3090 3100 3110 3120 3130 3140 3150cgagcacagg ctggaagcgg cctgcaactg gacgcggggc gaacgctgtg atctggaaga cagggacagg3160 3170 3180 3190 3200 3210 3220tccgagctca gcccgttact gctgtccacc acgcagtggc aggtccttcc gtgttctttc acgaccctgc3230 3240 3250 3260 3270 3280 3290cagcctaatc tagagggccc tattctatag tgtcacctaa atgctagagg atctttgtga aggaacctta3300 3310 3320 3330 3340 3350 3360cttctgtggt gtgacataat tggacaaact acctacagag atttaaagct ctaaggtaaa tataaaattt3370 3380 3390 3400 3410 3420 3430ttaagtgtat aatgtgttaa actactgatt ctaattgttt gtgtatttta gattccaacc tatggaactg3440 3450 3460 3470 3480 3490 3500atgaatggga gcagtggtgg aatgccttta atgaggaaaa cctgttttgc tcagaagaaa tgccatctag3510 3520 3530 3540 3550 3560 3570tgatgatgag gctactgctg actctcaaca ttctactcct ccaaaaaaga agagaaaggt agaagacccc3580 3590 3600 3610 3620 3630 3640aaggactttc cttcagaatt gctaagtttt ttgagtcatg ctgtgtttag taatagaact cttgcttgct3650 3660 3670 3680 3690 3700 3710ttgctattta caccacaaag gaaaaagctg cactgctata caagaaaatt atggaaaaat attctgtaac3720 3730 3740 3750 3760 3770 3780ctttataagt aggcataaca gttataatca taacatactg ttttttctta ctccacacag gcatagagtg3790 3800 3810 3820 3830 3840 3850tctgctatta ataactatgc tcaaaaattg tgtaccttta gctttttaat ttgtaaaggg gttaataagg3860 3870 3880 3890 3900 3910 3920aatatttgat gtatagtgcc ttgactagag atcataatca gccataccac atttgtagag gttttacttg3930 3940 3950 3960 2970 3980 3990ctttaaaaaa cctcccacac ctccccctga acctgaaaca taaaatgaat gcaattgttg ttgttaactt4000 4010 4020 4030 4040 4050 4060gtttattgca gcttataatg gttacaaata aagcaatagc atcacaaatt tcacaaataa agcatttttt4070 4080 4090 4100 4110 4120 4130tcactgcatt ctagttgtgg tttgtccaaa ctcatcaatg tatcttatca tgtctggatc gatcccgcca4140 4150 4160 4170 4180 4190 4200tggtatcaac gccatatttc tatttacagt agggacctct tcgttgtgta ggtaccgctg tattcctagg4210 4220 4230 4240 4250 4260 4270gaaatagtag aggcaccttg aactgtctgc atcagccata tagcccccgc tgttcgactt acaaacacag4280 4290 4300 4310 4320 4330 4340gcacagtact gacaaaccca tacacctcct ctgaaatacc catagttgct agggctgtct ccgaactcat4350 4360 4370 4380 4390 4400 4410tacaccctcc aaagtcagag ctgtaatttc gccatcaagg gcagcgaggg cttctccaga taaaatagct4420 4430 4440 4450 4460 4470 4480tctgccgaga gtcccgtaag ggtagacact tcagctaatc cctcgatgag gtctactaga atagtcagtg4490 4500 4510 4520 4530 4540 4550cggctcccat tttgaaaatt cacttacttg atcagcttca gaagatggcg gagggcctcc aacacagtaa4560 4570 4580 4590 4600 4610 4620ttttcctccc gactcttaaa atagaaaatg tcaagtcagt taagcaggaa gtggactaac tgacgcagct4630 4640 4650 4660 4670 4680 4690ggccgtgcga catcctcttt taattagttg ctaggcaacg ccctccagag ggcgtgtggt tttgcaagag4700 4710 4720 4730 4740 4750 4760gaagcaaaag cctctccacc caggcctaga atgtttccac ccaatcatta ctatgacaac agctgttttt4770 4780 4790 4800 4810 4820 4830tttagtatta agcagaggcc ggggacccct ggcccgctta ctctggagaa aaagaagaga ggcattgtag4840 4850 4860 4870 4880 4890 4900aggcttccag aggcaacttg tcaaaacagg actgcttcta tttctgtcac actgtctggc cctgtcacaa4910 4920 4930 4940 4950 4960 4970ggtccagcac ctccataccc cctttaataa gcagtttggg aacgggtgcg ggtcttactc cgcccatccc4980 4990 5000 5010 5020 5030 5040gcccctaact ccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat ttatgcagag5050 5060 5070 5080 5090 5100 5110gccgaggccg cctcggcctc tgagctattc cagaagtagt gaggaggctt ttttggaggc ctaggctttt5120gcaaaaagct aattcseq : __________________________________________________________________________seq . id . no . 12phcv - 17010 20 30 40 50 60 70matgsrtsll lafgllclpw lqegsaaaaa nsethvtggs aghttaglvr llspgakqni qlintngswh80 90 100 110 120 130 140instalncne slntgwlagl fyhhkfnssg cperlascrr ltdfaqgggp isyangsgld erpycwhypp150 160 170 150 190 200 210rpcgivpaks vcgpvycftp spvvvgttdr sgaptyswga ndtdvfvlnn trpplgnwfg ctwmnstgft220 230 240 250 260 270 280kvcgappcvi ggvgnntllc ptdcfrkhpe atysrcgsgp witprcmvdy pyrlwhypct inytifkvrm290 300 310 320 330yvggvehrle aacnwtrger cdledrdrse lsplllsttq wqvlpcsftt lpa . pep : __________________________________________________________________________ __________________________________________________________________________sequence listing ( 1 ) general information :( iii ) number of sequences : 12 ( 2 ) information for seq id no : 1 :( i ) sequence characteristics :( a ) length : 3011 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 1 : 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( 2 ) information for seq id no : 3 :( i ) sequence characteristics :( a ) length : 7298 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : circular ( ii ) molecule type : dna ( genomic )( ix ) feature :( a ) name / key : cds ( b ) location : 922 .. 2532 ( xi ) sequence description : seq id no : 3 : 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ctg2892tgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctgg2952aaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctga3012gtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattggg3072aagacaatagcaggcatgctggggatgcggtgggctctatggaaccagctggggctcgag3132gggggatccccacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcg3192cagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttc3252ctttctcgccacgttcgccggctttccccgtcaagctctaaatcggggcatccctttagg3312gttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttc3372acgtagtgggccatcgccctgatagacggtttttcgcctttactgagcactctttaatag3432tggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgattt3492ataagatttccatcgccatgtaaaagtgttacaattagcattaaattacttctttatatg3552ctactattcttttggcttcgttcacggggtgggtaccgagctcgaattctgtggaatgtg3612tgtcagttagggtgtggaaagtccccaggctccccaggcaggcagaagtatgcaaagcat3672gcatctcaattagtcagcaaccaggtgtggaaagtccccaggctccccagcaggcagaag3732tatgcaaagcatgcatctcaattagtcagcaaccatagtcccgcccctaactccgcccat3792cccgcccctaactccgcccagttccgcccattctccgccccatggctgactaattttttt3852tatttatgcagaggccgaggccgcctcggcctctgagctattccagaagtagtgaggagg3912cttttttggaggcctaggcttttgcaaaaagctcccgggagcttggatatccattttcgg3972atctgatcaagagacaggatgaggatcgtttcgcatgattgaacaagatggattgcacgc4032aggttctccggccgcttgggtggagaggctattcggctatgactgggcacaacagacaat4092cggctgctctgatgccgccgtgttccggctgtcagcgcaggggcgcccggttctttttgt4152caagaccgacctgtccggtgccctgaatgaactgcaggacgaggcagcgcggctatcgtg4212gctggccacgacgggcgttccttgcgcagctgtgctcgacgttgtcactgaagcgggaag4272ggactggctgctattgggcgaagtgccggggcaggatctcctgtcatctcaccttgctcc4332tgccgagaaagtatccatcatggctgatgcaatgcggcggctgcatacgcttgatccggc4392tacctgcccattcgaccaccaagcgaaacatcgcatcgagcgagcacgtactcggatgga4452agccggtcttgtcgatcaggatgatctggacgaagagcatcaggggctcgcgccagccga4512actgttcgccaggctcaaggcgcgcatgcccgacggcgaggatctcgtcgtgacccatgg4572cgatgcctgcttgccgaatatcatggtggaaaatggccgcttttctggattcatcgactg4632tggccggctgggtgtggcggaccgctatcaggacatagcgttggctacccgtgatattgc4692tgaagagcttggcggcgaatgggctgaccgcttcctcgtgctttacggtatcgccgctcc4752cgattcgcagcgcatcgccttctatcgccttcttgacgagttcttctgagcgggactctg4812gggttcgaaatgaccgaccaagcgacgcccaacctgccatcacgagatttcgattccacc4872gccgccttctatgaaaggttgggcttcggaatcgttttccgggacgccggctggatgatc4932ctccagcgcggggatctcatgctggagttcttcgcccaccccaacttgtttattgcagct4992tataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttca5052ctgcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtctggatcccg5112tcgacctcgagagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatc5172cgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcct5232aatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaa5292acctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgta5352ttgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggc5412gagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacg5472caggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgt5532tgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaa5592gtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagct5652ccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcc5712cttcgggaagcgtggcgctttctcaatgctcacgctgtaggtatctcagttcggtgtagg5772tcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgcct5832tatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcag5892cagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttga5952agtggtggcctaactacggctacactagaaggacagtatttggtatctgcgctctgctga6012agccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctg6072gtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaag6132aagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaag6192ggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaat6252gaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgct6312taatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgac6372tccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaa6432tgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccg6492gaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaatt6552gttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgcca6612ttgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggtt6672cccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctcct6732tcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatgg6792cagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtg6852agtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccgg6912cgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaa6972aacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgt7032aacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggt7092gagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgtt7152gaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctca7212tgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacat7272ttccccgaaaagtgccacctgacgtc7298 ( 2 ) information for seq id no : 4 :( i ) sequence characteristics :( a ) length : 537 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 4 : metleuproglyleualaleuleuleuleualaalatrpthralaarg151015alaleugluvalprothraspglyasnalaglyleuleualaglupro202530glnilealametphecysglyargleuasnmethismetasnvalgln354045asnglylystrpaspseraspproserglythrlysthrcysileasp505560thrlysgluthrhisvalthrglyglyseralaglyhisthrthrala65707580glyleuvalargleuleuserproglyalalysglnasnileglnleu859095ileasnthrasnglysertrphisileasnserthralaleuasncys100105110asngluserleuasnthrglytrpleualaglyleuphetyrhishis115120125lyspheasnserserglycysprogluargleualasercysargarg130135140leuthraspphealaglnglyglyglyproilesertyralaasngly145150155160serglyleuaspgluargprotyrcystrphistyrproproargpro165170175cysglyilevalproalalysservalcysglyprovaltyrcysphe180185190thrproserprovalvalvalglythrthraspargserglyalapro195200205thrtyrsertrpglyalaasnaspthraspvalphevalleuasnasn210215220thrargproproleuglyasntrppheglycysthrtrpmetasnser225230235240thrglyphethrlysvalcysglyalaproprocysvalileglygly245250255valglyasnasnthrleuleucysprothraspcysphearglyshis260265270proglualathrtyrserargcysglyserglyprotrpilethrpro275280285argcysmetvalasptyrprotyrargleutrphistyrprocysthr290295300ileasntyrthrilephelysvalargmettyrvalglyglyvalglu305310315320hisargleuglualaalacysasntrpthrargglygluargcysasp325330335leugluaspargaspargsergluleuserproleuleuleuserthr340345350thrglntrpglnvalleuprocysserphethrthrleuproalaleu355360365serthrglyleuilehisleuhisglnasnilevalaspvalglntyr370375380leutyrglyvalglyserserilealasertrpalailelystrpglu385390395400tyraspvalleuleupheleuleuleualaaspalaargvalcysser405410415cysleutrpmetmetleuleuileserglnalaglualaalaleuglu420425430ilesergluvallysmetaspalagluphearghisaspserglytyr435440445gluvalhishisglnlysleuvalphephealagluaspvalglyser450455460asnlysglyalaileileglyleumetvalglyglyvalvalileala465470475480thrvalilevalilethrleuvalmetleulyslyslysglntyrthr485490495serilehishisglyvalvalgluvalaspalaalavalthrproglu500505510gluarghisleuserlysmetglnglnasnglytyrgluasnprothr515520525tyrlysphephegluglnmetglnasn530535 ( 2 ) information for seq id no : 5 :( i ) sequence characteristics :( a ) length : 7106 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : circular ( ii ) molecule type : dna ( genomic )( ix ) feature :( a ) name / key : cds ( b ) location : 922 .. 2022 ( xi ) sequence description : seq id no : 5 : gacggatcgggagatctcccgatcccctatggtcgactctcagtacaatctgctctgatg60ccgcatagttaagccagtatctgctccctgcttgtgtgttggaggtcgctgagtagtgcg120cgagcaaaatttaagctacaacaaggcaaggcttgaccgacaattgcatgaagaatctgc180ttagggttaggcgttttgcgctgcttcgcgatgtacgggccagatatacgcgttgacatt240gattattgactagttattaatagtaatcaattacggggtcattagttcatagcccatata300tggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacc360cccgcccattgacgtcaataatgacgtatgttcccatagtaacgccaatagggactttcc420attgacgtcaatgggtggactatttacggtaaactgcccacttggcagtacatcaagtgt480atcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctggcatt540atgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagtca600tcgctattaccatggtgatgcggttttggcagtacatcaatgggcgtggatagcggtttg660actcacggggatttccaagtctccaccccattgacgtcaatgggagtttgttttggcacc720aaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcg780gtaggcgtgtacggtgggaggtctatataagcagagctctctggctaactagagaaccca840ctgcttaactggcttatcgaaattaatacgactcactatagggagaccggaagctttgct900ctagactggaattcgggcgcgatgctgcccggtttggcactgctcctgctg951metleuproglyleualaleuleuleuleu1510gccgcctggacggctcgggcgctggaggtacccactgatggtaatgct999alaalatrpthralaargalaleugluvalprothraspglyasnala152025ggcctgctggctgaaccccagattgccatgttctgtggcagactgaac1047glyleuleualagluproglnilealametphecysglyargleuasn303540atgcacatgaatgtccagaatgggaagtgggattcagatccatcaggg1095methismetasnvalglnasnglylystrpaspseraspprosergly455055accaaaacctgcattgataccaaggaaacccacgtcaccgggggaagt1143thrlysthrcysileaspthrlysgluthrhisvalthrglyglyser606570gccggccacaccacggctgggcttgttcgtctcctttcaccaggcgcc1191alaglyhisthrthralaglyleuvalargleuleuserproglyala75808590aagcagaacatccaactgatcaacaccaacggcagttggcacatcaat1239lysglnasnileglnleuileasnthrasnglysertrphisileasn95100105agcacggccttgaactgcaatgaaagccttaacaccggctggttagca1287serthralaleuasncysasngluserleuasnthrglytrpleuala110115120gggctcttctatcaccacaaattcaactcttcaggttgtcctgagagg1335glyleuphetyrhishislyspheasnserserglycysprogluarg125130135ttggccagctgccgacgccttaccgattttgcccagggcgggggtcct1383leualasercysargargleuthraspphealaglnglyglyglypro140145150atcagttacgccaacggaagcggcctcgatgaacgcccctactgctgg1431ilesertyralaasnglyserglyleuaspgluargprotyrcystrp155160165170cactaccctccaagaccttgtggcattgtgcccgcaaagagcgtgtgt1479histyrproproargprocysglyilevalproalalysservalcys175180185ggcccggtatattgcttcactcccagccccgtggtggtgggaacgacc1527glyprovaltyrcysphethrproserprovalvalvalglythrthr190195200gacaggtcgggcgcgcctacctacagctggggtgcaaatgatacggat1575aspargserglyalaprothrtyrsertrpglyalaasnaspthrasp205210215gtctttgtccttaacaacaccaggccaccgctgggcaattggttcggt1623valphevalleuasnasnthrargproproleuglyasntrpphegly220225230tgcacctggatgaactcaactggattcaccaaagtgtgcggagcgccc1671cysthrtrpmetasnserthrglyphethrlysvalcysglyalapro235240245250ccttgtgtcatcggaggggtgggcaacaacaccttgctctgccccact1719procysvalileglyglyvalglyasnasnthrleuleucysprothr255260265gattgcttccgcaagcatccggaagccacatactctcggtgcggctcc1767aspcysphearglyshisproglualathrtyrserargcysglyser270275280ggtccctggattacacccaggtgcatggtcgactacccgtataggctt1815glyprotrpilethrproargcysmetvalasptyrprotyrargleu285290295tggcactatccttgtaccatcaattacaccatattcaaagtcaggatg1863trphistyrprocysthrileasntyrthrilephelysvalargmet300305310tacgtgggaggggtcgagcacaggctggaagcggcctgcaactggacg1911tyrvalglyglyvalgluhisargleuglualaalacysasntrpthr315320325330cggggcgaacgctgtgatctggaagacagggacaggtccgagctcagc1959argglygluargcysaspleugluaspargaspargsergluleuser335340345ccgttactgctgtccaccacgcagtggcaggtccttccgtgttctttc2007proleuleuleuserthrthrglntrpglnvalleuprocysserphe350355360acgaccctgccagcctagatctctgaagtgaagatggatgcagaattccgacatg2062thrthrleuproala365actcaggatatgaagttcatcatcaaaaattggtgttctttgcagaagatgtgggttcaa2122acaaaggtgcaatcattggactcatggtgggcggtgttgtcatagcgacagtgatcgtca2182tcaccttggtgatgctgaagaagaaacagtacacatccattcatcatggtgtggtggagg2242ttgacgccgctgtcaccccagaggagcgccacctgtccaagatgcagcagaacggctacg2302aaaatccaacctacaagttctttgagcagatgcagaactagacccccgccacagcagcct2362ctgaagttggacagcaaaaccattgcttcactacccatcggtgtccatttatagaataat2422gtgggaagaaacaaacccgttttatgatttactcattatcgccttttgacagctgtgctg2482taacacaagtagatgcctgaacttgaattaatccacacatcagtaatgtattctatctct2542ctttacattttggtctctatactacattattaatgggttttgtgtactgtaaagaattta2602gctgtatcaaactagtgcatgaataggccgctcgagcatgcatctagagggccctattct2662atagtgtcacctaaatgctcgctgatcagcctcgactgtgccttctagttgccagccatc2722tgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcct2782ttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggg2842gggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgg2902ggatgcggtgggctctatggaaccagctggggctcgaggggggatccccacgcgccctgt2962agcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgcc3022agcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggc3082tttccccgtcaagctctaaatcggggcatccctttagggttccgatttagtgctttacgg3142cacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccctga3202tagacggtttttcgcctttactgagcactctttaatagtggactcttgttccaaactgga3262acaacactcaaccctatctcggtctattcttttgatttataagatttccatcgccatgta3322aaagtgttacaattagcattaaattacttctttatatgctactattcttttggcttcgtt3382cacggggtgggtaccgagctcgaattctgtggaatgtgtgtcagttagggtgtggaaagt3442ccccaggctccccaggcaggcagaagtatgcaaagcatgcatctcaattagtcagcaacc3502aggtgtggaaagtccccaggctccccagcaggcagaagtatgcaaagcatgcatctcaat3562tagtcagcaaccatagtcccgcccctaactccgcccatcccgcccctaactccgcccagt3622tccgcccattctccgccccatggctgactaattttttttatttatgcagaggccgaggcc3682gcctcggcctctgagctattccagaagtagtgaggaggcttttttggaggcctaggcttt3742tgcaaaaagctcccgggagcttggatatccattttcggatctgatcaagagacaggatga3802ggatcgtttcgcatgattgaacaagatggattgcacgcaggttctccggccgcttgggtg3862gagaggctattcggctatgactgggcacaacagacaatcggctgctctgatgccgccgtg3922ttccggctgtcagcgcaggggcgcccggttctttttgtcaagaccgacctgtccggtgcc3982ctgaatgaactgcaggacgaggcagcgcggctatcgtggctggccacgacgggcgttcct4042tgcgcagctgtgctcgacgttgtcactgaagcgggaagggactggctgctattgggcgaa4102gtgccggggcaggatctcctgtcatctcaccttgctcctgccgagaaagtatccatcatg4162gctgatgcaatgcggcggctgcatacgcttgatccggctacctgcccattcgaccaccaa4222gcgaaacatcgcatcgagcgagcacgtactcggatggaagccggtcttgtcgatcaggat4282gatctggacgaagagcatcaggggctcgcgccagccgaactgttcgccaggctcaaggcg4342cgcatgcccgacggcgaggatctcgtcgtgacccatggcgatgcctgcttgccgaatatc4402atggtggaaaatggccgcttttctggattcatcgactgtggccggctgggtgtggcggac4462cgctatcaggacatagcgttggctacccgtgatattgctgaagagcttggcggcgaatgg4522gctgaccgcttcctcgtgctttacggtatcgccgctcccgattcgcagcgcatcgccttc4582tatcgccttcttgacgagttcttctgagcgggactctggggttcgaaatgaccgaccaag4642cgacgcccaacctgccatcacgagatttcgattccaccgccgccttctatgaaaggttgg4702gcttcggaatcgttttccgggacgccggctggatgatcctccagcgcggggatctcatgc4762tggagttcttcgcccaccccaacttgtttattgcagcttataatggttacaaataaagca4822atagcatcacaaatttcacaaataaagcatttttttcactgcattctagttgtggtttgt4882ccaaactcatcaatgtatcttatcatgtctggatcccgtcgacctcgagagcttggcgta4942atcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacat5002acgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacatt5062aattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcatta5122atgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctc5182gctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaa5242ggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaa5302aggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggct5362ccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgac5422aggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttcc5482gaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttc5542tcaatgctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctg5602tgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttga5662gtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattag5722cagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggcta5782cactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaag5842agttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttg5902caagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctac5962ggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatc6022aaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaag6082tatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctc6142agcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactac6202gatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctc6262accggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtgg6322tcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaag6382tagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtc6442acgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttac6502atgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcag6562aagtaagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttac6622tgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctg6682agaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgc6742gccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaact6802ctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactg6862atcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaa6922tgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttt6982tcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatg7042tatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctga7102cgtc7106 ( 2 ) information for seq id no : 6 :( i ) sequence characteristics :( a ) length : 367 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 6 : metleuproglyleualaleuleuleuleualaalatrpthralaarg151015alaleugluvalprothraspglyasnalaglyleuleualaglupro202530glnilealametphecysglyargleuasnmethismetasnvalgln354045asnglylystrpaspseraspproserglythrlysthrcysileasp505560thrlysgluthrhisvalthrglyglyseralaglyhisthrthrala65707580glyleuvalargleuleuserproglyalalysglnasnileglnleu859095ileasnthrasnglysertrphisileasnserthralaleuasncys100105110asngluserleuasnthrglytrpleualaglyleuphetyrhishis115120125lyspheasnserserglycysprogluargleualasercysargarg130135140leuthraspphealaglnglyglyglyproilesertyralaasngly145150155160serglyleuaspgluargprotyrcystrphistyrproproargpro165170175cysglyilevalproalalysservalcysglyprovaltyrcysphe180185190thrproserprovalvalvalglythrthraspargserglyalapro195200205thrtyrsertrpglyalaasnaspthraspvalphevalleuasnasn210215220thrargproproleuglyasntrppheglycysthrtrpmetasnser225230235240thrglyphethrlysvalcysglyalaproprocysvalileglygly245250255valglyasnasnthrleuleucysprothraspcysphearglyshis260265270proglualathrtyrserargcysglyserglyprotrpilethrpro275280285argcysmetvalasptyrprotyrargleutrphistyrprocysthr290295300ileasntyrthrilephelysvalargmettyrvalglyglyvalglu305310315320hisargleuglualaalacysasntrpthrargglygluargcysasp325330335leugluaspargaspargsergluleuserproleuleuleuserthr340345350thrglntrpglnvalleuprocysserphethrthrleuproala355360365 ( 2 ) information for seq id no : 7 :( i ) sequence characteristics :( a ) length : 4810 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : circular ( ii ) molecule type : dna ( genomic )( ix ) feature :( a ) name / key : cds ( b ) location : 2227 .. 2910 ( xi ) sequence description : seq id no : 7 : gcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccgg60atcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaa120atactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgc180ctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgt240gtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaa300cggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacc360tacagcgtgagcattgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatc420cggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcct480ggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgat540gctcgtcaggggggcggagcctatggaaaaacgccagcaacgcaagctagcttctagcta600gaaattgtaaacgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctca660ttttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagcccgag720atagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactcc780aacgtcaaagggcgaaaaaccgtctatcagggcgatggccgcccactacgtgaaccatca840cccaaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaaggg900agcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaag960aaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaacc1020accacacccgccgcgcttaatgcgccgctacagggcgcgtactatggttgctttgacgag1080accgtataacgtgctttcctcgttggaatcagagcgggagctaaacaggaggccgattaa1140agggattttagacaggaacggtacgccagctggatcaccgcggtctttctcaacgtaaca1200ctttacagcggcgcgtcatttgatatgatgcgccccgcttcccgataagggagcaggcca1260gtaaaagcattacccgtggtggggttcccgagcggccaaagggagcagactctaaatctg1320ccgtcatcgacttcgaaggttcgaatccttcccccaccaccatcactttcaaaagtccga1380aagaatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagtaaaatttaa1440gctacaacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgt1500tttgcgctgcttcgcgatgtacgggccagatatacgcgttgacattgattattgactagt1560tattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgtt1620acataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacg1680tcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgg1740gtggactatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagt1800acgccccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatg1860accttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatg1920gtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggattt1980ccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggac2040tttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacgg2100tgggaggtctatataagcagagctctctggctaactagagaacccactgcttaactggct2160tatcgaaattaatacgactcactatagggagaccggaagcttggtaccgagctcggatct2220gccaccatggcaacaggatcaagaacatcactgctgctggcatttgga2268metalathrglyserargthrserleuleuleualaphegly1510ctgctgtgtctgccatggctgcaagaaggatcagcagcagcagcagcg2316leuleucysleuprotrpleuglngluglyseralaalaalaalaala15202530aattcggatccctaccaagtgcgcaattcctcggggctttaccatgtc2364asnseraspprotyrglnvalargasnserserglyleutyrhisval354045accaatgattgccctaattcgagtattgtgtacgaggcggccgatgcc2412thrasnaspcysproasnserserilevaltyrglualaalaaspala505560atcctacacactccggggtgtgtcccttgcgttcgcgagggtaacgcc2460ileleuhisthrproglycysvalprocysvalarggluglyasnala657075tcgaggtgttgggtggcggtgacccccacggtggccaccagggacggc2508serargcystrpvalalavalthrprothrvalalathrargaspgly808590aaactccccacaacgcagcttcgacgtcatatcgatctgctcgtcggg2556lysleuprothrthrglnleuargarghisileaspleuleuvalgly95100105110agcgccaccctctgctcggccctctacgtgggggacctgtgcgggtct2604seralathrleucysseralaleutyrvalglyaspleucysglyser115120125gtctttcttgttggtcaactgtttaccttctctcccaggcgccactgg2652valpheleuvalglyglnleuphethrpheserproargarghistrp130135140acgacgcaagactgcaattgttctatctatcccggccatataacgggt2700thrthrglnaspcysasncysseriletyrproglyhisilethrgly145150155catcgtatggcatgggatatgatgatgaactggtcccctacggcagcg2748hisargmetalatrpaspmetmetmetasntrpserprothralaala160165170ttggtggtagctcagctgctccggatcccacaagccatcttggacatg2796leuvalvalalaglnleuleuargileproglnalaileleuaspmet175180185190atcgctggtgcccactggggagtcctggcgggcatagcgtatttctcc2844ilealaglyalahistrpglyvalleualaglyilealatyrpheser195200205atggtggggaactgggcgaaggtcctggtagtgctgctgctatttgcc2892metvalglyasntrpalalysvalleuvalvalleuleuleupheala210215220ggcgttgacgcggagatctaatctagagggccctattctatagtgtca2940glyvalaspalagluile225cctaaatgctagaggatctttgtgaaggaaccttacttctgtggtgtgacataattggac3000aaactacctacagagatttaaagctctaaggtaaatataaaatttttaagtgtataatgt3060gttaaactactgattctaattgtttgtgtattttagattccaacctatggaactgatgaa3120tgggagcagtggtggaatgcctttaatgaggaaaacctgttttgctcagaagaaatgcca3180tctagtgatgatgaggctactgctgactctcaacattctactcctccaaaaaagaagaga3240aaggtagaagaccccaaggactttccttcagaattgctaagttttttgagtcatgctgtg3300tttagtaatagaactcttgcttgctttgctatttacaccacaaaggaaaaagctgcactg3360ctatacaagaaaattatggaaaaatattctgtaacctttataagtaggcataacagttat3420aatcataacatactgttttttcttactccacacaggcatagagtgtctgctattaataac3480tatgctcaaaaattgtgtacctttagctttttaatttgtaaaggggttaataaggaatat3540ttgatgtatagtgccttgactagagatcataatcagccataccacatttgtagaggtttt3600acttgctttaaaaaacctcccacacctccccctgaacctgaaacataaaatgaatgcaat3660tgttgttgttaacttgtttattgcagcttataatggttacaaataaagcaatagcatcac3720aaatttcacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcat3780caatgtatcttatcatgtctggatcgatcccgccatggtatcaacgccatatttctattt3840acagtagggacctcttcgttgtgtaggtaccgctgtattcctagggaaatagtagaggca3900ccttgaactgtctgcatcagccatatagcccccgctgttcgacttacaaacacaggcaca3960gtactgacaaacccatacacctcctctgaaatacccatagttgctagggctgtctccgaa4020ctcattacaccctccaaagtcagagctgtaatttcgccatcaagggcagcgagggcttct4080ccagataaaatagcttctgccgagagtcccgtaagggtagacacttcagctaatccctcg4140atgaggtctactagaatagtcagtgcggctcccattttgaaaattcacttacttgatcag4200cttcagaagatggcggagggcctccaacacagtaattttcctcccgactcttaaaataga4260aaatgtcaagtcagttaagcaggaagtggactaactgacgcagctggccgtgcgacatcc4320tcttttaattagttgctaggcaacgccctccagagggcgtgtggttttgcaagaggaagc4380aaaagcctctccacccaggcctagaatgtttccacccaatcattactatgacaacagctg4440ttttttttagtattaagcagaggccggggacccctggcccgcttactctggagaaaaaga4500agagaggcattgtagaggcttccagaggcaacttgtcaaaacaggactgcttctatttct4560gtcacactgtctggccctgtcacaaggtccagcacctccataccccctttaataagcagt4620ttgggaacgggtgcgggtcttactccgcccatcccgcccctaactccgcccagttccgcc4680cattctccgccccatggctgactaattttttttatttatgcagaggccgaggccgcctcg4740gcctctgagctattccagaagtagtgaggaggcttttttggaggcctaggcttttgcaaa4800aagctaattc4810 ( 2 ) information for seq id no : 8 :( i ) sequence characteristics :( a ) length : 228 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 8 : metalathrglyserargthrserleuleuleualapheglyleuleu151015cysleuprotrpleuglngluglyseralaalaalaalaalaasnser202530aspprotyrglnvalargasnserserglyleutyrhisvalthrasn354045aspcysproasnserserilevaltyrglualaalaaspalaileleu505560histhrproglycysvalprocysvalarggluglyasnalaserarg65707580cystrpvalalavalthrprothrvalalathrargaspglylysleu859095prothrthrglnleuargarghisileaspleuleuvalglyserala100105110thrleucysseralaleutyrvalglyaspleucysglyservalphe115120125leuvalglyglnleuphethrpheserproargarghistrpthrthr130135140glnaspcysasncysseriletyrproglyhisilethrglyhisarg145150155160metalatrpaspmetmetmetasntrpserprothralaalaleuval165170175valalaglnleuleuargileproglnalaileleuaspmetileala180185190glyalahistrpglyvalleualaglyilealatyrphesermetval195200205glyasntrpalalysvalleuvalvalleuleuleuphealaglyval210215220aspalagluile225 ( 2 ) information for seq id no : 9 :( i ) sequence characteristics :( a ) length : 5323 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : circular ( ii ) molecule type : dna ( genomic )( ix ) feature :( a ) name / key : cds ( b ) location : 2227 .. 3423 ( xi ) sequence description : seq id no : 9 : gcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccgg60atcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaa120atactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgc180ctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgt240gtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaa300cggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacc360tacagcgtgagcattgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatc420cggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcct480ggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgat540gctcgtcaggggggcggagcctatggaaaaacgccagcaacgcaagctagcttctagcta600gaaattgtaaacgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctca660ttttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagcccgag720atagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactcc780aacgtcaaagggcgaaaaaccgtctatcagggcgatggccgcccactacgtgaaccatca840cccaaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaaggg900agcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaag960aaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaacc1020accacacccgccgcgcttaatgcgccgctacagggcgcgtactatggttgctttgacgag1080accgtataacgtgctttcctcgttggaatcagagcgggagctaaacaggaggccgattaa1140agggattttagacaggaacggtacgccagctggatcaccgcggtctttctcaacgtaaca1200ctttacagcggcgcgtcatttgatatgatgcgccccgcttcccgataagggagcaggcca1260gtaaaagcattacccgtggtggggttcccgagcggccaaagggagcagactctaaatctg1320ccgtcatcgacttcgaaggttcgaatccttcccccaccaccatcactttcaaaagtccga1380aagaatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagtaaaatttaa1440gctacaacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgt1500tttgcgctgcttcgcgatgtacgggccagatatacgcgttgacattgattattgactagt1560tattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgtt1620acataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacg1680tcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgg1740gtggactatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagt1800acgccccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatg1860accttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatg1920gtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggattt1980ccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggac2040tttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacgg2100tgggaggtctatataagcagagctctctggctaactagagaacccactgcttaactggct2160tatcgaaattaatacgactcactatagggagaccggaagcttggtaccgagctcggatct2220gccaccatggcaacaggatcaagaacatcactgctgctggcatttgga2268metalathrglyserargthrserleuleuleualaphegly1510ctgctgtgtctgccatggctgcaagaaggatcagcagcagcagcagcg2316leuleucysleuprotrpleuglngluglyseralaalaalaalaala15202530aattcagaaacccacgtcaccgggggaagtgccggccacaccacggct2364asnsergluthrhisvalthrglyglyseralaglyhisthrthrala354045gggcttgttcgtctcctttcaccaggcgccaagcagaacatccaactg2412glyleuvalargleuleuserproglyalalysglnasnileglnleu505560atcaacaccaacggcagttggcacatcaatagcacggccttgaactgc2460ileasnthrasnglysertrphisileasnserthralaleuasncys657075aatgaaagccttaacaccggctggttagcagggctcttctatcaccac2508asngluserleuasnthrglytrpleualaglyleuphetyrhishis808590aaattcaactcttcaggttgtcctgagaggttggccagctgccgacgc2556lyspheasnserserglycysprogluargleualasercysargarg95100105110cttaccgattttgcccagggcgggggtcctatcagttacgccaacgga2604leuthraspphealaglnglyglyglyproilesertyralaasngly115120125agcggcctcgatgaacgcccctactgctggcactaccctccaagacct2652serglyleuaspgluargprotyrcystrphistyrproproargpro130135140tgtggcattgtgcccgcaaagagcgtgtgtggcccggtatattgcttc2700cysglyilevalproalalysservalcysglyprovaltyrcysphe145150155actcccagccccgtggtggtgggaacgaccgacaggtcgggcgcgcct2748thrproserprovalvalvalglythrthraspargserglyalapro160165170acctacagctggggtgcaaatgatacggatgtctttgtccttaacaac2796thrtyrsertrpglyalaasnaspthraspvalphevalleuasnasn175180185190accaggccaccgctgggcaattggttcggttgcacctggatgaactca2844thrargproproleuglyasntrppheglycysthrtrpmetasnser195200205actggattcaccaaagtgtgcggagcgcccccttgtgtcatcggaggg2892thrglyphethrlysvalcysglyalaproprocysvalileglygly210215220gtgggcaacaacaccttgctctgccccactgattgcttccgcaagcat2940valglyasnasnthrleuleucysprothraspcysphearglyshis225230235ccggaagccacatactctcggtgcggctccggtccctggattacaccc2988proglualathrtyrserargcysglyserglyprotrpilethrpro240245250aggtgcatggtcgactacccgtataggctttggcactatccttgtacc3036argcysmetvalasptyrprotyrargleutrphistyrprocysthr255260265270atcaattacaccatattcaaagtcaggatgtacgtgggaggggtcgag3084ileasntyrthrilephelysvalargmettyrvalglyglyvalglu275280285cacaggctggaagcggcctgcaactggacgcggggcgaacgctgtgat3132hisargleuglualaalacysasntrpthrargglygluargcysasp290295300ctggaagacagggacaggtccgagctcagcccgttactgctgtccacc3180leugluaspargaspargsergluleuserproleuleuleuserthr305310315acgcagtggcaggtccttccgtgttctttcacgaccctgccagccttg3228thrglntrpglnvalleuprocysserphethrthrleuproalaleu320325330tccaccggcctcatccacctccaccagaacattgtggacgtgcagtac3276serthrglyleuilehisleuhisglnasnilevalaspvalglntyr335340345350ttgtacggggtagggtcaagcatcgcgtcctgggctattaagtgggag3324leutyrglyvalglyserserilealasertrpalailelystrpglu355360365tacgacgttctcctgttccttctgcttgcagacgcgcgcgtttgctcc3372tyraspvalleuleupheleuleuleualaaspalaargvalcysser370375380tgcttgtggatgatgttactcatatcccaagcggaggcggctttggag3420cysleutrpmetmetleuleuileserglnalaglualaalaleuglu385390395aactaatctagagggccctattctatagtgtcacctaaatgctagaggatctt3473asntgtgaaggaaccttacttctgtggtgtgacataattggacaaactacctacagagattta3533aagctctaaggtaaatataaaatttttaagtgtataatgtgttaaactactgattctaat3593tgtttgtgtattttagattccaacctatggaactgatgaatgggagcagtggtggaatgc3653ctttaatgaggaaaacctgttttgctcagaagaaatgccatctagtgatgatgaggctac3713tgctgactctcaacattctactcctccaaaaaagaagagaaaggtagaagaccccaagga3773ctttccttcagaattgctaagttttttgagtcatgctgtgtttagtaatagaactcttgc3833ttgctttgctatttacaccacaaaggaaaaagctgcactgctatacaagaaaattatgga3893aaaatattctgtaacctttataagtaggcataacagttataatcataacatactgttttt3953tcttactccacacaggcatagagtgtctgctattaataactatgctcaaaaattgtgtac4013ctttagctttttaatttgtaaaggggttaataaggaatatttgatgtatagtgccttgac4073tagagatcataatcagccataccacatttgtagaggttttacttgctttaaaaaacctcc4133cacacctccccctgaacctgaaacataaaatgaatgcaattgttgttgttaacttgttta4193ttgcagcttataatggttacaaataaagcaatagcatcacaaatttcacaaataaagcat4253ttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtct4313ggatcgatcccgccatggtatcaacgccatatttctatttacagtagggacctcttcgtt4373gtgtaggtaccgctgtattcctagggaaatagtagaggcaccttgaactgtctgcatcag4433ccatatagcccccgctgttcgacttacaaacacaggcacagtactgacaaacccatacac4493ctcctctgaaatacccatagttgctagggctgtctccgaactcattacaccctccaaagt4553cagagctgtaatttcgccatcaagggcagcgagggcttctccagataaaatagcttctgc4613cgagagtcccgtaagggtagacacttcagctaatccctcgatgaggtctactagaatagt4673cagtgcggctcccattttgaaaattcacttacttgatcagcttcagaagatggcggaggg4733cctccaacacagtaattttcctcccgactcttaaaatagaaaatgtcaagtcagttaagc4793aggaagtggactaactgacgcagctggccgtgcgacatcctcttttaattagttgctagg4853caacgccctccagagggcgtgtggttttgcaagaggaagcaaaagcctctccacccaggc4913ctagaatgtttccacccaatcattactatgacaacagctgttttttttagtattaagcag4973aggccggggacccctggcccgcttactctggagaaaaagaagagaggcattgtagaggct5033tccagaggcaacttgtcaaaacaggactgcttctatttctgtcacactgtctggccctgt5093cacaaggtccagcacctccataccccctttaataagcagtttgggaacgggtgcgggtct5153tactccgcccatcccgcccctaactccgcccagttccgcccattctccgccccatggctg5213actaattttttttatttatgcagaggccgaggccgcctcggcctctgagctattccagaa5273gtagtgaggaggcttttttggaggcctaggcttttgcaaaaagctaattc5323 ( 2 ) information for seq id no : 10 :( i ) sequence characteristics :( a ) length : 399 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 10 : metalathrglyserargthrserleuleuleualapheglyleuleu151015cysleuprotrpleuglngluglyseralaalaalaalaalaasnser202530gluthrhisvalthrglyglyseralaglyhisthrthralaglyleu354045valargleuleuserproglyalalysglnasnileglnleuileasn505560thrasnglysertrphisileasnserthralaleuasncysasnglu65707580serleuasnthrglytrpleualaglyleuphetyrhishislysphe859095asnserserglycysprogluargleualasercysargargleuthr100105110aspphealaglnglyglyglyproilesertyralaasnglysergly115120125leuaspgluargprotyrcystrphistyrproproargprocysgly130135140ilevalproalalysservalcysglyprovaltyrcysphethrpro145150155160serprovalvalvalglythrthraspargserglyalaprothrtyr165170175sertrpglyalaasnaspthraspvalphevalleuasnasnthrarg180185190proproleuglyasntrppheglycysthrtrpmetasnserthrgly195200205phethrlysvalcysglyalaproprocysvalileglyglyvalgly210215220asnasnthrleuleucysprothraspcysphearglyshisproglu225230235240alathrtyrserargcysglyserglyprotrpilethrproargcys245250255metvalasptyrprotyrargleutrphistyrprocysthrileasn260265270tyrthrilephelysvalargmettyrvalglyglyvalgluhisarg275280285leuglualaalacysasntrpthrargglygluargcysaspleuglu290295300aspargaspargsergluleuserproleuleuleuserthrthrgln305310315320trpglnvalleuprocysserphethrthrleuproalaleuserthr325330335glyleuilehisleuhisglnasnilevalaspvalglntyrleutyr340345350glyvalglyserserilealasertrpalailelystrpglutyrasp355360365valleuleupheleuleuleualaaspalaargvalcyssercysleu370375380trpmetmetleuleuileserglnalaglualaalaleugluasn385390395 ( 2 ) information for seq id no : 11 :( i ) sequence characteristics :( a ) length : 5125 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : circular ( ii ) molecule type : dna ( genomic )( ix ) feature :( a ) name / key : cds ( b ) location : 2227 .. 3225 ( xi ) sequence description : seq id no : 11 : gcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccgg60atcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaa120atactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgc180ctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgt240gtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaa300cggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacc360tacagcgtgagcattgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatc420cggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcct480ggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgat540gctcgtcaggggggcggagcctatggaaaaacgccagcaacgcaagctagcttctagcta600gaaattgtaaacgttaatattttgttaaaattcgcgttaaatttttgttaaatcagctca660ttttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagcccgag720atagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactcc780aacgtcaaagggcgaaaaaccgtctatcagggcgatggccgcccactacgtgaaccatca840cccaaatcaagttttttggggtcgaggtgccgtaaagcactaaatcggaaccctaaaggg900agcccccgatttagagcttgacggggaaagccggcgaacgtggcgagaaaggaagggaag960aaagcgaaaggagcgggcgctagggcgctggcaagtgtagcggtcacgctgcgcgtaacc1020accacacccgccgcgcttaatgcgccgctacagggcgcgtactatggttgctttgacgag1080accgtataacgtgctttcctcgttggaatcagagcgggagctaaacaggaggccgattaa1140agggattttagacaggaacggtacgccagctggatcaccgcggtctttctcaacgtaaca1200ctttacagcggcgcgtcatttgatatgatgcgccccgcttcccgataagggagcaggcca1260gtaaaagcattacccgtggtggggttcccgagcggccaaagggagcagactctaaatctg1320ccgtcatcgacttcgaaggttcgaatccttcccccaccaccatcactttcaaaagtccga1380aagaatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagtaaaatttaa1440gctacaacaaggcaaggcttgaccgacaattgcatgaagaatctgcttagggttaggcgt1500tttgcgctgcttcgcgatgtacgggccagatatacgcgttgacattgattattgactagt1560tattaatagtaatcaattacggggtcattagttcatagcccatatatggagttccgcgtt1620acataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacg1680tcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgg1740gtggactatttacggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagt1800acgccccctattgacgtcaatgacggtaaatggcccgcctggcattatgcccagtacatg1860accttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatg1920gtgatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggattt1980ccaagtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggac2040tttccaaaatgtcgtaacaactccgccccattgacgcaaatgggcggtaggcgtgtacgg2100tgggaggtctatataagcagagctctctggctaactagagaacccactgcttaactggct2160tatcgaaattaatacgactcactatagggagaccggaagcttggtaccgagctcggatct2220gccaccatggcaacaggatcaagaacatcactgctgctggcatttgga2268metalathrglyserargthrserleuleuleualaphegly1510ctgctgtgtctgccatggctgcaagaaggatcagcagcagcagcagcg2316leuleucysleuprotrpleuglngluglyseralaalaalaalaala15202530aattcagaaacccacgtcaccgggggaagtgccggccacaccacggct2364asnsergluthrhisvalthrglyglyseralaglyhisthrthrala354045gggcttgttcgtctcctttcaccaggcgccaagcagaacatccaactg2412glyleuvalargleuleuserproglyalalysglnasnileglnleu505560atcaacaccaacggcagttggcacatcaatagcacggccttgaactgc2460ileasnthrasnglysertrphisileasnserthralaleuasncys657075aatgaaagccttaacaccggctggttagcagggctcttctatcaccac2508asngluserleuasnthrglytrpleualaglyleuphetyrhishis808590aaattcaactcttcaggttgtcctgagaggttggccagctgccgacgc2556lyspheasnserserglycysprogluargleualasercysargarg95100105110cttaccgattttgcccagggcgggggtcctatcagttacgccaacgga2604leuthraspphealaglnglyglyglyproilesertyralaasngly115120125agcggcctcgatgaacgcccctactgctggcactaccctccaagacct2652serglyleuaspgluargprotyrcystrphistyrproproargpro130135140tgtggcattgtgcccgcaaagagcgtgtgtggcccggtatattgcttc2700cysglyilevalproalalysservalcysglyprovaltyrcysphe145150155actcccagccccgtggtggtgggaacgaccgacaggtcgggcgcgcct2748thrproserprovalvalvalglythrthraspargserglyalapro160165170acctacagctggggtgcaaatgatacggatgtctttgtccttaacaac2796thrtyrsertrpglyalaasnaspthraspvalphevalleuasnasn175180185190accaggccaccgctgggcaattggttcggttgcacctggatgaactca2844thrargproproleuglyasntrppheglycysthrtrpmetasnser195200205actggattcaccaaagtgtgcggagcgcccccttgtgtcatcggaggg2892thrglyphethrlysvalcysglyalaproprocysvalileglygly210215220gtgggcaacaacaccttgctctgccccactgattgcttccgcaagcat2940valglyasnasnthrleuleucysprothraspcysphearglyshis225230235ccggaagccacatactctcggtgcggctccggtccctggattacaccc2988proglualathrtyrserargcysglyserglyprotrpilethrpro240245250aggtgcatggtcgactacccgtataggctttggcactatccttgtacc3036argcysmetvalasptyrprotyrargleutrphistyrprocysthr255260265270atcaattacaccatattcaaagtcaggatgtacgtgggaggggtcgag3084ileasntyrthrilephelysvalargmettyrvalglyglyvalglu275280285cacaggctggaagcggcctgcaactggacgcggggcgaacgctgtgat3132hisargleuglualaalacysasntrpthrargglygluargcysasp290295300ctggaagacagggacaggtccgagctcagcccgttactgctgtccacc3180leugluaspargaspargsergluleuserproleuleuleuserthr305310315acgcagtggcaggtccttccgtgttctttcacgaccctgccagcc3225thrglntrpglnvalleuprocysserphethrthrleuproala320325330taatctagagggccctattctatagtgtcacctaaatgctagaggatctttgtgaaggaa3285ccttacttctgtggtgtgacataattggacaaactacctacagagatttaaagctctaag3345gtaaatataaaatttttaagtgtataatgtgttaaactactgattctaattgtttgtgta3405ttttagattccaacctatggaactgatgaatgggagcagtggtggaatgcctttaatgag3465gaaaacctgttttgctcagaagaaatgccatctagtgatgatgaggctactgctgactct3525caacattctactcctccaaaaaagaagagaaaggtagaagaccccaaggactttccttca3585gaattgctaagttttttgagtcatgctgtgtttagtaatagaactcttgcttgctttgct3645atttacaccacaaaggaaaaagctgcactgctatacaagaaaattatggaaaaatattct3705gtaacctttataagtaggcataacagttataatcataacatactgttttttcttactcca3765cacaggcatagagtgtctgctattaataactatgctcaaaaattgtgtacctttagcttt3825ttaatttgtaaaggggttaataaggaatatttgatgtatagtgccttgactagagatcat3885aatcagccataccacatttgtagaggttttacttgctttaaaaaacctcccacacctccc3945cctgaacctgaaacataaaatgaatgcaattgttgttgttaacttgtttattgcagctta4005taatggttacaaataaagcaatagcatcacaaatttcacaaataaagcatttttttcact4065gcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtctggatcgatcc4125cgccatggtatcaacgccatatttctatttacagtagggacctcttcgttgtgtaggtac4185cgctgtattcctagggaaatagtagaggcaccttgaactgtctgcatcagccatatagcc4245cccgctgttcgacttacaaacacaggcacagtactgacaaacccatacacctcctctgaa4305atacccatagttgctagggctgtctccgaactcattacaccctccaaagtcagagctgta4365atttcgccatcaagggcagcgagggcttctccagataaaatagcttctgccgagagtccc4425gtaagggtagacacttcagctaatccctcgatgaggtctactagaatagtcagtgcggct4485cccattttgaaaattcacttacttgatcagcttcagaagatggcggagggcctccaacac4545agtaattttcctcccgactcttaaaatagaaaatgtcaagtcagttaagcaggaagtgga4605ctaactgacgcagctggccgtgcgacatcctcttttaattagttgctaggcaacgccctc4665cagagggcgtgtggttttgcaagaggaagcaaaagcctctccacccaggcctagaatgtt4725tccacccaatcattactatgacaacagctgttttttttagtattaagcagaggccgggga4785cccctggcccgcttactctggagaaaaagaagagaggcattgtagaggcttccagaggca4845acttgtcaaaacaggactgcttctatttctgtcacactgtctggccctgtcacaaggtcc4905agcacctccataccccctttaataagcagtttgggaacgggtgcgggtcttactccgccc4965atcccgcccctaactccgcccagttccgcccattctccgccccatggctgactaattttt5025tttatttatgcagaggccgaggccgcctcggcctctgagctattccagaagtagtgagga5085ggcttttttggaggcctaggcttttgcaaaaagctaattc5125 ( 2 ) information for seq id no : 12 :( i ) sequence characteristics :( a ) length : 333 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 12 : metalathrglyserargthrserleuleuleualapheglyleuleu151015cysleuprotrpleuglngluglyseralaalaalaalaalaasnser202530gluthrhisvalthrglyglyseralaglyhisthrthralaglyleu354045valargleuleuserproglyalalysglnasnileglnleuileasn505560thrasnglysertrphisileasnserthralaleuasncysasnglu65707580serleuasnthrglytrpleualaglyleuphetyrhishislysphe859095asnserserglycysprogluargleualasercysargargleuthr100105110aspphealaglnglyglyglyproilesertyralaasnglysergly115120125leuaspgluargprotyrcystrphistyrproproargprocysgly130135140ilevalproalalysservalcysglyprovaltyrcysphethrpro145150155160serprovalvalvalglythrthraspargserglyalaprothrtyr165170175sertrpglyalaasnaspthraspvalphevalleuasnasnthrarg180185190proproleuglyasntrppheglycysthrtrpmetasnserthrgly195200205phethrlysvalcysglyalaproprocysvalileglyglyvalgly210215220asnasnthrleuleucysprothraspcysphearglyshisproglu225230235240alathrtyrserargcysglyserglyprotrpilethrproargcys245250255metvalasptyrprotyrargleutrphistyrprocysthrileasn260265270tyrthrilephelysvalargmettyrvalglyglyvalgluhisarg275280285leuglualaalacysasntrpthrargglygluargcysaspleuglu290295300aspargaspargsergluleuserproleuleuleuserthrthrgln305310315320trpglnvalleuprocysserphethrthrleuproala325330__________________________________________________________________________