                         SEQUENCE LISTINGS

<110>  Basilea Pharmaceutica AG
 
<120>  Process for the manufacture of Isavuconazole and Ravuconazole

<130>  WH/P41139EPPC

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  1650
<212>  DNA
<213>  artificial sequence

<220>
<223>  gene PLE variant SEQ ID No. 2, codon optimized


<220>
<221>  CDS
<222>  (1)..(1650)
<223>  PLE variant

<400>  1
atg gga caa cca gct tcg ccg cct gtc gtt gat acc gct caa gga cga         48
Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg           
1               5                   10                  15                

gtc ttg ggt aag tac gtc tct tta gag gga ttg gca caa ccg gtt gct         96
Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala           
            20                  25                  30                    

gtc ttc ttg gga gtc cct ttt gct aag cca cct ctt gga tct ttg agg        144
Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg           
        35                  40                  45                        

ttt gcc ccg ccg caa cca gca gag cca tgg tct ttc gtt aag aac act        192
Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr           
    50                  55                  60                            

act tcc tac cct cca atg tgt tgt caa gaa cca atc gga gga caa atg        240
Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met           
65                  70                  75                  80            

ctt tca gac cta ttc act aac aga aag gaa agg ctt atc ccg gag ttc        288
Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe           
                85                  90                  95                

tct gag gat tgc ctt tac cta aat att tac act cct gcc gat ttg aca        336
Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr           
            100                 105                 110                   

aag agg ggt agg ttg ccg gtt atg gtt tgg att cat gga gga ggt ttg        384
Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu           
        115                 120                 125                       

gtt gtt ggc gga gca tcc act tat gac gga ttg gct ctt gcc gcg cac        432
Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His           
    130                 135                 140                           

gag aac gtt gtt gtt gtt gct att caa tac cgt ttg ggt att tgg gga        480
Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly           
145                 150                 155                 160           

ttt ttc tcc aca gga gat gag cat tcc cgt gga aac tgg ggc cat tta        528
Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu           
                165                 170                 175               

gat caa gtt gct gca ttg cat tgg gtc caa gaa aac att gct aac ttc        576
Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe           
            180                 185                 190                   

gga ggt gat cca ggt tct gtt act att ttc gga gaa tca gca ggc gga        624
Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly           
        195                 200                 205                       

gag agt gtc tct gta ttg gtt tta tca cca tta gct aag aac ctt ttt        672
Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe           
    210                 215                 220                           

cat cgt gct att tcc gaa agt ggt gtt gct ttt acc gcc ggt gtg gtc        720
His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Val Val           
225                 230                 235                 240           

agg aag gat atg aag gcc gca gcc aag cag atc gct gtc ctt gca gga        768
Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly           
                245                 250                 255               

tgc aaa act act act tcg gca gtc ttc gtg cat tgt ttg cgt caa aag        816
Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys           
            260                 265                 270                   

tcg gaa gat gaa ctt tta gac ctc acg ttg aag atg aaa ttc ttt gcc        864
Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala           
        275                 280                 285                       

ctt gac tta cac gga gat cca agg gaa tct cac cct ttt ttg acc act        912
Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr           
    290                 295                 300                           

gtt gtt gac gga gtt ttg ttg cct aag atg cct gag gaa atc ttg gcc        960
Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala           
305                 310                 315                 320           

gag aag gac ttt aac acc gtc cca tac att gtt gga att aac aag cag       1008
Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln           
                325                 330                 335               

gag ttc gga tgg ctt ttg cca acg atg atg gga ttt cct ctt tcc gag       1056
Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu           
            340                 345                 350                   

gga aag ttg gat caa aag acg gct acg tca ctt ttg tgg aag tcc tac       1104
Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr           
        355                 360                 365                       

cca att gcc aac att cct gaa gag ttg acc cca gtt gct acc gat aag       1152
Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys           
    370                 375                 380                           

tat tta gga gga aca gat gat cct gtc aaa aag aaa gat ttg ttt ttg       1200
Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu           
385                 390                 395                 400           

gat ctg atg gga gac gtt gtt ttc ggc gtc cca tca gtt acg gtt gct       1248
Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala           
                405                 410                 415               

cgt cag cat agg gac gca gga gct cca act tac atg tat gag ttc caa       1296
Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln           
            420                 425                 430                   

tat cgt cca tct ttt tca tcg gat aag aaa cct aag acg gtt att gga       1344
Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly           
        435                 440                 445                       

gat cat gga gac gaa att ttt tcc gtc ttc ggc ttc cca ttg ctc aaa       1392
Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys           
    450                 455                 460                           

ggt gac gct cca gag gaa gaa gtc agt ctt tct aag acg gtt atg aaa       1440
Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys           
465                 470                 475                 480           

ttt tgg gct aac ttc gcc cgt agt gga aac cct aat gga gaa gga ttg       1488
Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu           
                485                 490                 495               

cct cac tgg ccg atg tac gat caa gag gag gga tac ctt caa att ggt       1536
Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly           
            500                 505                 510                   

gtc aac act caa gca gct aag agg ttg aaa ggc gag gag gtt gct ttt       1584
Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe           
        515                 520                 525                       

tgg aac gac ctg ttg tcc aag gaa gca gca aag aag cca cct aag ata       1632
Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile           
    530                 535                 540                           

aag cac gcc gaa ttg taa                                               1650
Lys His Ala Glu Leu                                                       
545                                                                       


<210>  2
<211>  549
<212>  PRT
<213>  artificial sequence

<220>
<223>  Synthetic Construct

<400>  2

Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg 
1               5                   10                  15      


Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala 
            20                  25                  30          


Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg 
        35                  40                  45              


Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr 
    50                  55                  60                  


Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met 
65                  70                  75                  80  


Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe 
                85                  90                  95      


Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr 
            100                 105                 110         


Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu 
        115                 120                 125             


Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His 
    130                 135                 140                 


Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly 
145                 150                 155                 160 


Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu 
                165                 170                 175     


Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe 
            180                 185                 190         


Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly 
        195                 200                 205             


Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe 
    210                 215                 220                 


His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Val Val 
225                 230                 235                 240 


Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly 
                245                 250                 255     


Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys 
            260                 265                 270         


Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala 
        275                 280                 285             


Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr 
    290                 295                 300                 


Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala 
305                 310                 315                 320 


Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln 
                325                 330                 335     


Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu 
            340                 345                 350         


Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr 
        355                 360                 365             


Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys 
    370                 375                 380                 


Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu 
385                 390                 395                 400 


Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala 
                405                 410                 415     


Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln 
            420                 425                 430         


Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly 
        435                 440                 445             


Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys 
    450                 455                 460                 


Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys 
465                 470                 475                 480 


Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu 
                485                 490                 495     


Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly 
            500                 505                 510         


Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe 
        515                 520                 525             


Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile 
    530                 535                 540                 


Lys His Ala Glu Leu 
545                 


<210>  3
<211>  1650
<212>  DNA
<213>  artificial sequence

<220>
<223>  gene APLE SEQ ID No. 4, codon optimized


<220>
<221>  CDS
<222>  (1)..(1650)
<223>  APLE

<400>  3
atg gga caa cca gct tcg ccg cct gtc gtt gat acc gct caa gga cga         48
Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg           
1               5                   10                  15                

gtc ttg ggt aag tac gtc tct tta gag gga ttg gca caa ccg gtt gct         96
Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala           
            20                  25                  30                    

gtc ttc ttg gga gtc cct ttt gct aag cca cct ctt gga tct ttg agg        144
Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg           
        35                  40                  45                        

ttt gcc ccg ccg caa cca gca gag cca tgg tct ttc gtt aag aac act        192
Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr           
    50                  55                  60                            

act tcc tac cct cca atg tgt tgt caa gaa cca atc gga gga caa atg        240
Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met           
65                  70                  75                  80            

ctt tca gac cta ttc act aac aga aag gaa agg ctt atc ccg gag ttc        288
Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe           
                85                  90                  95                

tct gag gat tgc ctt tac cta aat att tac act cct gcc gat ttg aca        336
Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr           
            100                 105                 110                   

aag agg ggt agg ttg ccg gtt atg gtt tgg att cat gga gga ggt ttg        384
Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu           
        115                 120                 125                       

gtt gtt ggc gga gca tcc act tat gac gga ttg gct ctt gcc gcg cac        432
Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His           
    130                 135                 140                           

gag aac gtt gtt gtt gtt gct att caa tac cgt ttg ggt att tgg gga        480
Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly           
145                 150                 155                 160           

ttt ttc tcc aca gga gat gag cat tcc cgt gga aac tgg ggc cat tta        528
Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu           
                165                 170                 175               

gat caa gtt gct gca ttg cat tgg gtc caa gaa aac att gct aac ttc        576
Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe           
            180                 185                 190                   

gga ggt gat cca ggt tct gtt act att ttc gga gaa tca gca ggc gga        624
Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly           
        195                 200                 205                       

gag agt gtc tct gta ttg gtt tta tca cca tta gct aag aac ctt ttt        672
Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe           
    210                 215                 220                           

cat cgt gct att tcc gaa agt ggt gtt gct ttt acc gcc ggt ttg gtc        720
His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val           
225                 230                 235                 240           

agg aag gat atg aag gcc gca gcc aag cag atc gct gtc ctt gca gga        768
Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly           
                245                 250                 255               

tgc aaa act act act tcg gca gtc ttc gtg cat tgt ttg cgt caa aag        816
Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys           
            260                 265                 270                   

tcg gaa gat gaa ctt tta gac ctc acg ttg aag atg aaa ttc ttt gcc        864
Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala           
        275                 280                 285                       

ctt gac tta cac gga gat cca agg gaa tct cac cct ttt ttg acc act        912
Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr           
    290                 295                 300                           

gtt gtt gac gga gtt ttg ttg cct aag atg cct gag gaa atc ttg gcc        960
Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala           
305                 310                 315                 320           

gag aag gac ttt aac acc gtc cca tac att gtt gga att aac aag cag       1008
Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln           
                325                 330                 335               

gag ttc gga tgg ctt ttg cca acg atg atg gga ttt cct ctt tcc gag       1056
Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu           
            340                 345                 350                   

gga aag ttg gat caa aag acg gct acg tca ctt ttg tgg aag tcc tac       1104
Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr           
        355                 360                 365                       

cca att gcc aac att cct gaa gag ttg acc cca gtt gct acc gat aag       1152
Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys           
    370                 375                 380                           

tat tta gga gga aca gat gat cct gtc aaa aag aaa gat ttg ttt ttg       1200
Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu           
385                 390                 395                 400           

gat ctg atg gga gac gtt gtt ttc ggc gtc cca tca gtt acg gtt gct       1248
Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala           
                405                 410                 415               

cgt cag cat agg gac gca gga gct cca act tac atg tat gag ttc caa       1296
Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln           
            420                 425                 430                   

tat cgt cca tct ttt tca tcg gat aag aaa cct aag acg gtt att gga       1344
Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly           
        435                 440                 445                       

gat cat gga gac gaa att ttt tcc gtc ttc ggc ttc cca ttg ctc aaa       1392
Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys           
    450                 455                 460                           

ggt gac gct cca gag gaa gaa gtc agt ctt tct aag acg gtt atg aaa       1440
Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys           
465                 470                 475                 480           

ttt tgg gct aac ttc gcc cgt agt gga aac cct aat gga gaa gga ttg       1488
Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu           
                485                 490                 495               

cct cac tgg ccg atg tac gat caa gag gag gga tac ctt caa att ggt       1536
Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly           
            500                 505                 510                   

gtc aac act caa gca gct aag agg ttg aaa ggc gag gag gtt gct ttt       1584
Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe           
        515                 520                 525                       

tgg aac gac ctg ttg tcc aag gaa gca gca aag aag cca cct aag ata       1632
Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile           
    530                 535                 540                           

aag cac gcc gaa ttg taa                                               1650
Lys His Ala Glu Leu                                                       
545                                                                       


<210>  4
<211>  549
<212>  PRT
<213>  artificial sequence

<220>
<223>  Synthetic Construct

<400>  4

Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg 
1               5                   10                  15      


Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala 
            20                  25                  30          


Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg 
        35                  40                  45              


Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr 
    50                  55                  60                  


Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met 
65                  70                  75                  80  


Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe 
                85                  90                  95      


Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr 
            100                 105                 110         


Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu 
        115                 120                 125             


Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His 
    130                 135                 140                 


Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly 
145                 150                 155                 160 


Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu 
                165                 170                 175     


Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe 
            180                 185                 190         


Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly 
        195                 200                 205             


Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe 
    210                 215                 220                 


His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val 
225                 230                 235                 240 


Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly 
                245                 250                 255     


Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys 
            260                 265                 270         


Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala 
        275                 280                 285             


Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr 
    290                 295                 300                 


Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala 
305                 310                 315                 320 


Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln 
                325                 330                 335     


Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu 
            340                 345                 350         


Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr 
        355                 360                 365             


Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys 
    370                 375                 380                 


Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu 
385                 390                 395                 400 


Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala 
                405                 410                 415     


Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln 
            420                 425                 430         


Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly 
        435                 440                 445             


Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys 
    450                 455                 460                 


Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys 
465                 470                 475                 480 


Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu 
                485                 490                 495     


Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly 
            500                 505                 510         


Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe 
        515                 520                 525             


Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile 
    530                 535                 540                 


Lys His Ala Glu Leu 
545                 


<210>  5
<211>  1650
<212>  DNA
<213>  artificial sequence

<220>
<223>  gene APLE Hybrid 3 SEQ ID No. 6, codon optimized


<220>
<221>  CDS
<222>  (1)..(1650)
<223>  APLE Hybrid 3

<400>  5
atg gga caa cca gct tcg ccg cct gtc gtt gat acc gct caa gga cga         48
Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg           
1               5                   10                  15                

gtc ttg ggt aag tac gtc tct tta gag gga ttg gca caa ccg gtt gct         96
Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala           
            20                  25                  30                    

gtc ttc ttg gga gtc cct ttt gct aag cca cct ctt gga tct ttg agg        144
Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg           
        35                  40                  45                        

ttt gcc ccg ccg caa cca gca gag cca tgg tct ttc gtt aag aac act        192
Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr           
    50                  55                  60                            

act tcc tac cct cca atg tgt tgt caa gaa cca atc gga gga caa atg        240
Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met           
65                  70                  75                  80            

ctt tca gac cta ttc act aac aga aag gaa agg ctt atc ccg gag ttc        288
Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe           
                85                  90                  95                

tct gag gat tgc ctt tac cta aat att tac act cct gcc gat ttg aca        336
Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr           
            100                 105                 110                   

aag agg ggt agg ttg ccg gtt atg gtt tgg att cat gga gga ggt ttg        384
Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu           
        115                 120                 125                       

gtt gtt ggc gga gca tcc act tat gac gga ttg gct ctt gcc gcg cac        432
Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His           
    130                 135                 140                           

gag aac gtt gtt gtt gtt gct att caa tac cgt ttg ggt att tgg gga        480
Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly           
145                 150                 155                 160           

ttt ttc tcc aca gga gat gag cat tcc cgt gga aac tgg ggc cat tta        528
Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu           
                165                 170                 175               

gat caa gtt gct gca ttg cat tgg gtc caa gaa aac att gct aac ttc        576
Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe           
            180                 185                 190                   

gga ggt gat cca ggt tct gtt act att ttc gga gaa tca gca ggc gga        624
Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly           
        195                 200                 205                       

gag agt gtc tct gta ttg gtt tta tca cca tta gct aag aac ctt ttt        672
Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe           
    210                 215                 220                           

cat cgt gct att tcc gaa agt ggt gtt gct tta acc gtc gct ttg gtc        720
His Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Thr Val Ala Leu Val           
225                 230                 235                 240           

agg aag gat atg aag gcc gca gcc aag cag atc gct gtc ctt gca gga        768
Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly           
                245                 250                 255               

tgc aaa act act act tcg gca gtc ttc gtg cat tgt ttg cgt caa aag        816
Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys           
            260                 265                 270                   

tcg gaa gat gaa ctt tta gac ctc acg ttg aag atg aaa ttc ttt gcc        864
Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala           
        275                 280                 285                       

ctt gac tta cac gga gat cca agg gaa tct cac cct ttt ttg acc act        912
Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr           
    290                 295                 300                           

gtt gtt gac gga gtt ttg ttg cct aag atg cct gag gaa atc ttg gcc        960
Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala           
305                 310                 315                 320           

gag aag gac ttt aac acc gtc cca tac att gtt gga att aac aag cag       1008
Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln           
                325                 330                 335               

gag ttc gga tgg ctt ttg cca acg atg atg gga ttt cct ctt tcc gag       1056
Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu           
            340                 345                 350                   

gga aag ttg gat caa aag acg gct acg tca ctt ttg tgg aag tcc tac       1104
Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr           
        355                 360                 365                       

cca att gcc aac att cct gaa gag ttg acc cca gtt gct acc gat aag       1152
Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys           
    370                 375                 380                           

tat tta gga gga aca gat gat cct gtc aaa aag aaa gat ttg ttt ttg       1200
Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu           
385                 390                 395                 400           

gat ctg atg gga gac gtt gtt ttc ggc gtc cca tca gtt acg gtt gct       1248
Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala           
                405                 410                 415               

cgt cag cat agg gac gca gga gct cca act tac atg tat gag ttc caa       1296
Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln           
            420                 425                 430                   

tat cgt cca tct ttt tca tcg gat aag aaa cct aag acg gtt att gga       1344
Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly           
        435                 440                 445                       

gat cat gga gac gaa att ttt tcc gtc ttc ggc ttc cca ttg ctc aaa       1392
Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys           
    450                 455                 460                           

ggt gac gct cca gag gaa gaa gtc agt ctt tct aag acg gtt atg aaa       1440
Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys           
465                 470                 475                 480           

ttt tgg gct aac ttc gcc cgt agt gga aac cct aat gga gaa gga ttg       1488
Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu           
                485                 490                 495               

cct cac tgg ccg atg tac gat caa gag gag gga tac ctt caa att ggt       1536
Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly           
            500                 505                 510                   

gtc aac act caa gca gct aag agg ttg aaa ggc gag gag gtt gct ttt       1584
Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe           
        515                 520                 525                       

tgg aac gac ctg ttg tcc aag gaa gca gca aag aag cca cct aag ata       1632
Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile           
    530                 535                 540                           

aag cac gcc gaa ttg taa                                               1650
Lys His Ala Glu Leu                                                       
545                                                                       


<210>  6
<211>  549
<212>  PRT
<213>  artificial sequence

<220>
<223>  Synthetic Construct

<400>  6

Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg 
1               5                   10                  15      


Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala 
            20                  25                  30          


Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg 
        35                  40                  45              


Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr 
    50                  55                  60                  


Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met 
65                  70                  75                  80  


Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe 
                85                  90                  95      


Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr 
            100                 105                 110         


Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu 
        115                 120                 125             


Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His 
    130                 135                 140                 


Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly 
145                 150                 155                 160 


Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu 
                165                 170                 175     


Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe 
            180                 185                 190         


Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly 
        195                 200                 205             


Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe 
    210                 215                 220                 


His Arg Ala Ile Ser Glu Ser Gly Val Ala Leu Thr Val Ala Leu Val 
225                 230                 235                 240 


Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly 
                245                 250                 255     


Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys 
            260                 265                 270         


Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala 
        275                 280                 285             


Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr 
    290                 295                 300                 


Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala 
305                 310                 315                 320 


Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln 
                325                 330                 335     


Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu 
            340                 345                 350         


Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr 
        355                 360                 365             


Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys 
    370                 375                 380                 


Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu 
385                 390                 395                 400 


Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala 
                405                 410                 415     


Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln 
            420                 425                 430         


Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly 
        435                 440                 445             


Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys 
    450                 455                 460                 


Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys 
465                 470                 475                 480 


Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu 
                485                 490                 495     


Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly 
            500                 505                 510         


Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe 
        515                 520                 525             


Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile 
    530                 535                 540                 


Lys His Ala Glu Leu 
545                 


<210>  7
<211>  1650
<212>  DNA
<213>  artificial sequence

<220>
<223>  gene APLE Hybrid 1 SEQ ID No. 8


<220>
<221>  CDS
<222>  (1)..(1650)
<223>  APLE Hybrid 1

<400>  7
atg gga caa cca gct tcg ccg cct gtc gtt gat acc gct caa gga cga         48
Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg           
1               5                   10                  15                

gtc ttg ggt aag tac gtc tct tta gag gga ttg gca caa ccg gtt gct         96
Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala           
            20                  25                  30                    

gtc ttc ttg gga gtc cct ttt gct aag cca cct ctt gga tct ttg agg        144
Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg           
        35                  40                  45                        

ttt gcc ccg ccg caa cca gca gag cca tgg tct ttc gtt aag aac act        192
Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr           
    50                  55                  60                            

act tcc tac cct cca atg tgt tgt caa gat cca gtc gta gaa caa atg        240
Thr Ser Tyr Pro Pro Met Cys Cys Gln Asp Pro Val Val Glu Gln Met           
65                  70                  75                  80            

acg tca gac cta ttc act aac gga aag gaa agg ctt acc ctg gag ttc        288
Thr Ser Asp Leu Phe Thr Asn Gly Lys Glu Arg Leu Thr Leu Glu Phe           
                85                  90                  95                

tct gag gat tgc ctt tac cta aat att tac act cct gcc gat ttg aca        336
Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr           
            100                 105                 110                   

aag agg ggt agg ttg ccg gtt atg gtt tgg att cat gga gga ggt ttg        384
Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu           
        115                 120                 125                       

gtt gtt ggc gga gca tcc act tat gac gga ttg gct ctt gcc gcg cac        432
Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His           
    130                 135                 140                           

gag aac gtt gtt gtt gtt gct att caa tac cgt ttg ggt att tgg gga        480
Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly           
145                 150                 155                 160           

ttt ttc tcc aca gga gat gag cat tcc cgt gga aac tgg ggc cat tta        528
Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu           
                165                 170                 175               

gat caa gtt gct gca ttg cat tgg gtc caa gaa aac att gct aac ttc        576
Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe           
            180                 185                 190                   

gga ggt gat cca ggt tct gtt act att ttc gga gaa tca gca ggc gga        624
Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly           
        195                 200                 205                       

gag agt gtc tct gta ttg gtt tta tca cca tta gct aag aac ctt ttt        672
Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe           
    210                 215                 220                           

cat cgt gct att tcc gaa agt ggt gtt gct ttt acc gcc ggt ttg gtc        720
His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val           
225                 230                 235                 240           

agg aag gat atg aag gcc gca gcc aag cag atc gct gtc ctt gca gga        768
Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly           
                245                 250                 255               

tgc aaa act act act tcg gca gtc ttc gtg cat tgt ttg cgt caa aag        816
Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys           
            260                 265                 270                   

tcg gaa gat gaa ctt tta gac ctc acg ttg aag atg aaa ttc ttt gcc        864
Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala           
        275                 280                 285                       

ctt gac tta cac gga gat cca agg gaa tct cac cct ttt ttg acc act        912
Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr           
    290                 295                 300                           

gtt gtt gac gga gtt ttg ttg cct aag atg cct gag gaa atc ttg gcc        960
Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala           
305                 310                 315                 320           

gag aag gac ttt aac acc gtc cca tac att gtt gga att aac aag cag       1008
Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln           
                325                 330                 335               

gag ttc gga tgg ctt ttg cca acg atg atg gga ttt cct ctt tcc gag       1056
Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu           
            340                 345                 350                   

gga aag ttg gat caa aag acg gct acg tca ctt ttg tgg aag tcc tac       1104
Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr           
        355                 360                 365                       

cca att gcc aac att cct gaa gag ttg acc cca gtt gct acc gat aag       1152
Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys           
    370                 375                 380                           

tat tta gga gga aca gat gat cct gtc aaa aag aaa gat ttg ttt ttg       1200
Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu           
385                 390                 395                 400           

gat ctg atg gga gac gtt gtt ttc ggc gtc cca tca gtt acg gtt gct       1248
Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala           
                405                 410                 415               

cgt cag cat agg gac gca gga gct cca act tac atg tat gag ttc caa       1296
Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln           
            420                 425                 430                   

tat cgt cca tct ttt tca tcg gat aag aaa cct aag acg gtt att gga       1344
Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly           
        435                 440                 445                       

gat cat gga gac gaa att ttt tcc gtc ttc ggc ttc cca ttg ctc aaa       1392
Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys           
    450                 455                 460                           

ggt gac gct cca gag gaa gaa gtc agt ctt tct aag acg gtt atg aaa       1440
Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys           
465                 470                 475                 480           

ttt tgg gct aac ttc gcc cgt agt gga aac cct aat gga gaa gga ttg       1488
Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu           
                485                 490                 495               

cct cac tgg ccg atg tac gat caa gag gag gga tac ctt caa att ggt       1536
Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly           
            500                 505                 510                   

gtc aac act caa gca gct aag agg ttg aaa ggc gag gag gtt gct ttt       1584
Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe           
        515                 520                 525                       

tgg aac gac ctg ttg tcc aag gaa gca gca aag aag cca cct aag ata       1632
Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile           
    530                 535                 540                           

aag cac gcc gaa ttg taa                                               1650
Lys His Ala Glu Leu                                                       
545                                                                       


<210>  8
<211>  549
<212>  PRT
<213>  artificial sequence

<220>
<223>  Synthetic Construct

<400>  8

Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg 
1               5                   10                  15      


Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala 
            20                  25                  30          


Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg 
        35                  40                  45              


Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr 
    50                  55                  60                  


Thr Ser Tyr Pro Pro Met Cys Cys Gln Asp Pro Val Val Glu Gln Met 
65                  70                  75                  80  


Thr Ser Asp Leu Phe Thr Asn Gly Lys Glu Arg Leu Thr Leu Glu Phe 
                85                  90                  95      


Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr 
            100                 105                 110         


Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu 
        115                 120                 125             


Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His 
    130                 135                 140                 


Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly 
145                 150                 155                 160 


Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu 
                165                 170                 175     


Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe 
            180                 185                 190         


Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly 
        195                 200                 205             


Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe 
    210                 215                 220                 


His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val 
225                 230                 235                 240 


Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly 
                245                 250                 255     


Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys 
            260                 265                 270         


Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala 
        275                 280                 285             


Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr 
    290                 295                 300                 


Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala 
305                 310                 315                 320 


Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln 
                325                 330                 335     


Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu 
            340                 345                 350         


Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr 
        355                 360                 365             


Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys 
    370                 375                 380                 


Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu 
385                 390                 395                 400 


Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala 
                405                 410                 415     


Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln 
            420                 425                 430         


Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly 
        435                 440                 445             


Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys 
    450                 455                 460                 


Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys 
465                 470                 475                 480 


Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu 
                485                 490                 495     


Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly 
            500                 505                 510         


Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe 
        515                 520                 525             


Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile 
    530                 535                 540                 


Lys His Ala Glu Leu 
545                 


<210>  9
<211>  1650
<212>  DNA
<213>  artificial sequence

<220>
<223>  gene PLE variant SEQ ID No. 10, codon optimized


<220>
<221>  CDS
<222>  (1)..(1650)
<223>  PLE variant

<400>  9
atg gga caa cca gct tcg ccg cct gtc gtt gat acc gct caa gga cga         48
Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg           
1               5                   10                  15                

gtc ttg ggt aag tac gtc tct tta gag gga ttg gca caa ccg gtt gct         96
Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala           
            20                  25                  30                    

gtc ttc ttg gga gtc cct ttt gct aag cca cct ctt gga tct ttg agg        144
Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg           
        35                  40                  45                        

ttt gcc ccg ccg caa cca gca gag cca tgg tct ttc gtt aag aac act        192
Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr           
    50                  55                  60                            

act tcc tac cct cca atg tgt tgt caa gaa cca atc gga gga caa atg        240
Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met           
65                  70                  75                  80            

ctt tca gac cta ttc act aac aga aag gaa agg ctt atc ccg gag ttc        288
Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe           
                85                  90                  95                

tct gag gat tgc ctt tac cta aat att tac act cct gcc gat ttg aca        336
Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr           
            100                 105                 110                   

aag agg ggt agg ttg ccg gtt atg gtt tgg att cat gga gga ggt ttg        384
Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu           
        115                 120                 125                       

gtt gtt ggc gga gca tcc act tat gac gga ttg gct ctt gcc gcg cac        432
Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His           
    130                 135                 140                           

gag aac gtt gtt gtt gtt gct att caa tac cgt ttg ggt att tgg gga        480
Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly           
145                 150                 155                 160           

ttt ttc tcc aca gga gat gag cat tcc cgt gga aac tgg ggc cat tta        528
Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu           
                165                 170                 175               

gat caa gtt gct gca ttg cat tgg gtc caa gaa aac att gct aac ttc        576
Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe           
            180                 185                 190                   

gga ggt gat cca ggt tct gtt act att ttc gga gaa tca gca ggc gga        624
Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly           
        195                 200                 205                       

gag agt gtc tct gta ttg gtt tta tca cca tta gct aag aac ctt ttt        672
Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe           
    210                 215                 220                           

cat cgt gct att tcc gaa agt ggt gtt gct ttt acc gcc ggt ttg gtc        720
His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val           
225                 230                 235                 240           

agg aag gat atg aag gcc gca gcc aag cag atc gct gtc ctt gca gga        768
Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly           
                245                 250                 255               

tgc aaa act act act tcg gca gac ttc gtg cat tgt ttg cgt caa aag        816
Cys Lys Thr Thr Thr Ser Ala Asp Phe Val His Cys Leu Arg Gln Lys           
            260                 265                 270                   

tcg gaa gat gaa ctt tta gac ctc acg ttg aag atg aaa ttc ttt gcc        864
Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala           
        275                 280                 285                       

ctt gac tta cac gga gat cca agg gaa tct cac cct ttt ttg acc act        912
Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr           
    290                 295                 300                           

gtt gtt gac gga gtt ttg ttg cct aag atg cct gag gaa atc ttg gcc        960
Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala           
305                 310                 315                 320           

gag aag gac ttt aac acc gtc cca tac att gtt gga att aac aag cag       1008
Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln           
                325                 330                 335               

gag ttc gga tgg ctt ttg cca acg atg atg gga ttt cct ctt tcc gag       1056
Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu           
            340                 345                 350                   

gga aag ttg gat caa aag acg gct acg tca ctt ttg tgg aag tcc tac       1104
Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr           
        355                 360                 365                       

cca att gcc aac att cct gaa gag ttg acc cca gtt gct acc gat aag       1152
Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys           
    370                 375                 380                           

tat tta gga gga aca gat gat cct gtc aaa aag aaa gat ttg ttt ttg       1200
Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu           
385                 390                 395                 400           

gat ctg atg gga gac gtt gtt ttc ggc gtc cca tca gtt acg gtt gct       1248
Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala           
                405                 410                 415               

cgt cag cat agg gac gca gga gct cca act tac atg tat gag ttc caa       1296
Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln           
            420                 425                 430                   

tat cgt cca tct ttt tca tcg gat aag aaa cct aag acg gtt att gga       1344
Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly           
        435                 440                 445                       

gat cat gga gac gaa att ttt tcc gtc ttc ggc ttc cca ttg ctc aaa       1392
Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys           
    450                 455                 460                           

ggt gac gct cca gag gaa gaa gtc agt ctt tct aag acg gtt atg aaa       1440
Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys           
465                 470                 475                 480           

ttt tgg gct aac ttc gcc cgt agt gga aac cct aat gga gaa gga ttg       1488
Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu           
                485                 490                 495               

cct cac tgg ccg atg tac gat caa gag gag gga tac ctt caa att ggt       1536
Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly           
            500                 505                 510                   

gtc aac act caa gca gct aag agg ttg aaa ggc gag gag gtt gct ttt       1584
Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe           
        515                 520                 525                       

tgg aac gac ctg ttg tcc aag gaa gca gca aag aag cca cct aag ata       1632
Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile           
    530                 535                 540                           

aag cac gcc gaa ttg taa                                               1650
Lys His Ala Glu Leu                                                       
545                                                                       


<210>  10
<211>  549
<212>  PRT
<213>  artificial sequence

<220>
<223>  Synthetic Construct

<400>  10

Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg 
1               5                   10                  15      


Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala 
            20                  25                  30          


Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg 
        35                  40                  45              


Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr 
    50                  55                  60                  


Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met 
65                  70                  75                  80  


Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe 
                85                  90                  95      


Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr 
            100                 105                 110         


Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu 
        115                 120                 125             


Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His 
    130                 135                 140                 


Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly 
145                 150                 155                 160 


Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu 
                165                 170                 175     


Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe 
            180                 185                 190         


Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly 
        195                 200                 205             


Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe 
    210                 215                 220                 


His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val 
225                 230                 235                 240 


Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly 
                245                 250                 255     


Cys Lys Thr Thr Thr Ser Ala Asp Phe Val His Cys Leu Arg Gln Lys 
            260                 265                 270         


Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Phe Ala 
        275                 280                 285             


Leu Asp Leu His Gly Asp Pro Arg Glu Ser His Pro Phe Leu Thr Thr 
    290                 295                 300                 


Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala 
305                 310                 315                 320 


Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln 
                325                 330                 335     


Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu 
            340                 345                 350         


Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr 
        355                 360                 365             


Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys 
    370                 375                 380                 


Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu 
385                 390                 395                 400 


Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala 
                405                 410                 415     


Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln 
            420                 425                 430         


Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly 
        435                 440                 445             


Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys 
    450                 455                 460                 


Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys 
465                 470                 475                 480 


Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu 
                485                 490                 495     


Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly 
            500                 505                 510         


Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe 
        515                 520                 525             


Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile 
    530                 535                 540                 


Lys His Ala Glu Leu 
545                 


<210>  11
<211>  1650
<212>  DNA
<213>  artificial sequence

<220>
<223>  gene APLE Hybrid 4 SEQ ID No. 12, codon optimized


<220>
<221>  CDS
<222>  (1)..(1650)
<223>  APLE Hybrid 4

<400>  11
atg gga caa cca gct tcg ccg cct gtc gtt gat acc gct caa gga cga         48
Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg           
1               5                   10                  15                

gtc ttg ggt aag tac gtc tct tta gag gga ttg gca caa ccg gtt gct         96
Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala           
            20                  25                  30                    

gtc ttc ttg gga gtc cct ttt gct aag cca cct ctt gga tct ttg agg        144
Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg           
        35                  40                  45                        

ttt gcc ccg ccg caa cca gca gag cca tgg tct ttc gtt aag aac act        192
Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr           
    50                  55                  60                            

act tcc tac cct cca atg tgt tgt caa gaa cca atc gga gga caa atg        240
Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met           
65                  70                  75                  80            

ctt tca gac cta ttc act aac aga aag gaa agg ctt atc ccg gag ttc        288
Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe           
                85                  90                  95                

tct gag gat tgc ctt tac cta aat att tac act cct gcc gat ttg aca        336
Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr           
            100                 105                 110                   

aag agg ggt agg ttg ccg gtt atg gtt tgg att cat gga gga ggt ttg        384
Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu           
        115                 120                 125                       

gtt gtt ggc gga gca tcc act tat gac gga ttg gct ctt gcc gcg cac        432
Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His           
    130                 135                 140                           

gag aac gtt gtt gtt gtt gct att caa tac cgt ttg ggt att tgg gga        480
Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly           
145                 150                 155                 160           

ttt ttc tcc aca gga gat gag cat tcc cgt gga aac tgg ggc cat tta        528
Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu           
                165                 170                 175               

gat caa gtt gct gca ttg cat tgg gtc caa gaa aac att gct aac ttc        576
Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe           
            180                 185                 190                   

gga ggt gat cca ggt tct gtt act att ttc gga gaa tca gca ggc gga        624
Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly           
        195                 200                 205                       

gag agt gtc tct gta ttg gtt tta tca cca tta gct aag aac ctt ttt        672
Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe           
    210                 215                 220                           

cat cgt gct att tcc gaa agt ggt gtt gct ttt acc gcc ggt ttg gtc        720
His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val           
225                 230                 235                 240           

agg aag gat atg aag gcc gca gcc aag cag atc gct gtc ctt gca gga        768
Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly           
                245                 250                 255               

tgc aaa act act act tcg gca gtc ttc gtg cat tgt ttg cgt caa aag        816
Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys           
            260                 265                 270                   

tcg gaa gat gaa ctt tta gac ctc acg ttg aag atg aaa ttc ctg acc        864
Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Leu Thr           
        275                 280                 285                       

ctt gac ttt cac gga gat caa agg gaa tct cac cct ttt ttg ccg act        912
Leu Asp Phe His Gly Asp Gln Arg Glu Ser His Pro Phe Leu Pro Thr           
    290                 295                 300                           

gtt gtt gac gga gtt ttg ttg cct aag atg cct gag gaa atc ttg gcc        960
Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala           
305                 310                 315                 320           

gag aag gac ttt aac acc gtc cca tac att gtt gga att aac aag cag       1008
Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln           
                325                 330                 335               

gag ttc gga tgg ctt ttg cca acg atg atg gga ttt cct ctt tcc gag       1056
Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu           
            340                 345                 350                   

gga aag ttg gat caa aag acg gct acg tca ctt ttg tgg aag tcc tac       1104
Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr           
        355                 360                 365                       

cca att gcc aac att cct gaa gag ttg acc cca gtt gct acc gat aag       1152
Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys           
    370                 375                 380                           

tat tta gga gga aca gat gat cct gtc aaa aag aaa gat ttg ttt ttg       1200
Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu           
385                 390                 395                 400           

gat ctg atg gga gac gtt gtt ttc ggc gtc cca tca gtt acg gtt gct       1248
Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala           
                405                 410                 415               

cgt cag cat agg gac gca gga gct cca act tac atg tat gag ttc caa       1296
Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln           
            420                 425                 430                   

tat cgt cca tct ttt tca tcg gat aag aaa cct aag acg gtt att gga       1344
Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly           
        435                 440                 445                       

gat cat gga gac gaa att ttt tcc gtc ttc ggc ttc cca ttg ctc aaa       1392
Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys           
    450                 455                 460                           

ggt gac gct cca gag gaa gaa gtc agt ctt tct aag acg gtt atg aaa       1440
Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys           
465                 470                 475                 480           

ttt tgg gct aac ttc gcc cgt agt gga aac cct aat gga gaa gga ttg       1488
Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu           
                485                 490                 495               

cct cac tgg ccg atg tac gat caa gag gag gga tac ctt caa att ggt       1536
Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly           
            500                 505                 510                   

gtc aac act caa gca gct aag agg ttg aaa ggc gag gag gtt gct ttt       1584
Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe           
        515                 520                 525                       

tgg aac gac ctg ttg tcc aag gaa gca gca aag aag cca cct aag ata       1632
Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile           
    530                 535                 540                           

aag cac gcc gaa ttg taa                                               1650
Lys His Ala Glu Leu                                                       
545                                                                       


<210>  12
<211>  549
<212>  PRT
<213>  artificial sequence

<220>
<223>  Synthetic Construct

<400>  12

Met Gly Gln Pro Ala Ser Pro Pro Val Val Asp Thr Ala Gln Gly Arg 
1               5                   10                  15      


Val Leu Gly Lys Tyr Val Ser Leu Glu Gly Leu Ala Gln Pro Val Ala 
            20                  25                  30          


Val Phe Leu Gly Val Pro Phe Ala Lys Pro Pro Leu Gly Ser Leu Arg 
        35                  40                  45              


Phe Ala Pro Pro Gln Pro Ala Glu Pro Trp Ser Phe Val Lys Asn Thr 
    50                  55                  60                  


Thr Ser Tyr Pro Pro Met Cys Cys Gln Glu Pro Ile Gly Gly Gln Met 
65                  70                  75                  80  


Leu Ser Asp Leu Phe Thr Asn Arg Lys Glu Arg Leu Ile Pro Glu Phe 
                85                  90                  95      


Ser Glu Asp Cys Leu Tyr Leu Asn Ile Tyr Thr Pro Ala Asp Leu Thr 
            100                 105                 110         


Lys Arg Gly Arg Leu Pro Val Met Val Trp Ile His Gly Gly Gly Leu 
        115                 120                 125             


Val Val Gly Gly Ala Ser Thr Tyr Asp Gly Leu Ala Leu Ala Ala His 
    130                 135                 140                 


Glu Asn Val Val Val Val Ala Ile Gln Tyr Arg Leu Gly Ile Trp Gly 
145                 150                 155                 160 


Phe Phe Ser Thr Gly Asp Glu His Ser Arg Gly Asn Trp Gly His Leu 
                165                 170                 175     


Asp Gln Val Ala Ala Leu His Trp Val Gln Glu Asn Ile Ala Asn Phe 
            180                 185                 190         


Gly Gly Asp Pro Gly Ser Val Thr Ile Phe Gly Glu Ser Ala Gly Gly 
        195                 200                 205             


Glu Ser Val Ser Val Leu Val Leu Ser Pro Leu Ala Lys Asn Leu Phe 
    210                 215                 220                 


His Arg Ala Ile Ser Glu Ser Gly Val Ala Phe Thr Ala Gly Leu Val 
225                 230                 235                 240 


Arg Lys Asp Met Lys Ala Ala Ala Lys Gln Ile Ala Val Leu Ala Gly 
                245                 250                 255     


Cys Lys Thr Thr Thr Ser Ala Val Phe Val His Cys Leu Arg Gln Lys 
            260                 265                 270         


Ser Glu Asp Glu Leu Leu Asp Leu Thr Leu Lys Met Lys Phe Leu Thr 
        275                 280                 285             


Leu Asp Phe His Gly Asp Gln Arg Glu Ser His Pro Phe Leu Pro Thr 
    290                 295                 300                 


Val Val Asp Gly Val Leu Leu Pro Lys Met Pro Glu Glu Ile Leu Ala 
305                 310                 315                 320 


Glu Lys Asp Phe Asn Thr Val Pro Tyr Ile Val Gly Ile Asn Lys Gln 
                325                 330                 335     


Glu Phe Gly Trp Leu Leu Pro Thr Met Met Gly Phe Pro Leu Ser Glu 
            340                 345                 350         


Gly Lys Leu Asp Gln Lys Thr Ala Thr Ser Leu Leu Trp Lys Ser Tyr 
        355                 360                 365             


Pro Ile Ala Asn Ile Pro Glu Glu Leu Thr Pro Val Ala Thr Asp Lys 
    370                 375                 380                 


Tyr Leu Gly Gly Thr Asp Asp Pro Val Lys Lys Lys Asp Leu Phe Leu 
385                 390                 395                 400 


Asp Leu Met Gly Asp Val Val Phe Gly Val Pro Ser Val Thr Val Ala 
                405                 410                 415     


Arg Gln His Arg Asp Ala Gly Ala Pro Thr Tyr Met Tyr Glu Phe Gln 
            420                 425                 430         


Tyr Arg Pro Ser Phe Ser Ser Asp Lys Lys Pro Lys Thr Val Ile Gly 
        435                 440                 445             


Asp His Gly Asp Glu Ile Phe Ser Val Phe Gly Phe Pro Leu Leu Lys 
    450                 455                 460                 


Gly Asp Ala Pro Glu Glu Glu Val Ser Leu Ser Lys Thr Val Met Lys 
465                 470                 475                 480 


Phe Trp Ala Asn Phe Ala Arg Ser Gly Asn Pro Asn Gly Glu Gly Leu 
                485                 490                 495     


Pro His Trp Pro Met Tyr Asp Gln Glu Glu Gly Tyr Leu Gln Ile Gly 
            500                 505                 510         


Val Asn Thr Gln Ala Ala Lys Arg Leu Lys Gly Glu Glu Val Ala Phe 
        515                 520                 525             


Trp Asn Asp Leu Leu Ser Lys Glu Ala Ala Lys Lys Pro Pro Lys Ile 
    530                 535                 540                 


Lys His Ala Glu Leu 
545                 


