1/11

                         SEQUENCE LISTING

<110>  Max-Planck Gesellschaft zur Frderung der Wissenschaften 
       e.V.
 
<120>  Polynucleotides encoding caryophyllene synthase and uses thereof

<130>  P2551 PCT S3

<150>  08 01 9870.7
<151>  2008-10-30

<160>  4     

<170>  PatentIn version 3.4

<210>  1
<211>  1665
<212>  DNA
<213>  Origanum vulgare


<220>
<221>  CDS
<222>  (1)..(1662)

<400>  1
atg gaa ttt ccg gca tcg gtt gct tcc ctt tcg gct aac acc gtc ggg       48
Met Glu Phe Pro Ala Ser Val Ala Ser Leu Ser Ala Asn Thr Val Gly         
1               5                   10                  15              

tcg aac gat gtt ctt cgt cgc tcc atc gct tac cat ccc aac att tgg       96
Ser Asn Asp Val Leu Arg Arg Ser Ile Ala Tyr His Pro Asn Ile Trp         
            20                  25                  30                  

gga gac ttt ttt ctt gcg cat act tca gaa ttt atg gaa atc tcg att      144
Gly Asp Phe Phe Leu Ala His Thr Ser Glu Phe Met Glu Ile Ser Ile         
        35                  40                  45                      

gct gaa aag gaa gag cac gaa cgg cta aaa gag gag atc aag aaa ctg      192
Ala Glu Lys Glu Glu His Glu Arg Leu Lys Glu Glu Ile Lys Lys Leu         
    50                  55                  60                          

ctc gtt caa act gag tat gat tcg ata ctt aaa tta gaa ctc atc gat      240
Leu Val Gln Thr Glu Tyr Asp Ser Ile Leu Lys Leu Glu Leu Ile Asp         
65                  70                  75                  80          

tca att caa cga ctt gga gtg ggt tac cat ttc gaa aaa gaa att gat      288
Ser Ile Gln Arg Leu Gly Val Gly Tyr His Phe Glu Lys Glu Ile Asp         
                85                  90                  95              

aga atc tta cga tat gtt cat caa acc tac cca ata tac gac acc gaa      336
Arg Ile Leu Arg Tyr Val His Gln Thr Tyr Pro Ile Tyr Asp Thr Glu         
            100                 105                 110                 

aac aag gat ctt cgt atg ctt gct cta cgc ttt cgc cta ctt cga caa      384
Asn Lys Asp Leu Arg Met Leu Ala Leu Arg Phe Arg Leu Leu Arg Gln         
        115                 120                 125                     

caa ggt ttc cat gtt cct ttc gat gtg ctt agt gaa ttc ata gat gcc      432
Gln Gly Phe His Val Pro Phe Asp Val Leu Ser Glu Phe Ile Asp Ala         
    130                 135                 140                         
2/11

gaa gga aat ctc acg gag tca ata gca tac gac att caa ggg ata ttg      480
Glu Gly Asn Leu Thr Glu Ser Ile Ala Tyr Asp Ile Gln Gly Ile Leu         
145                 150                 155                 160         

agc tta tat gag gca tca aat tat gga gtg ctc gga gag gaa att ctt      528
Ser Leu Tyr Glu Ala Ser Asn Tyr Gly Val Leu Gly Glu Glu Ile Leu         
                165                 170                 175             

gac aaa gca tta gat tcg tgc tcg tct cgt ctt gaa tcg tta atc acg      576
Asp Lys Ala Leu Asp Ser Cys Ser Ser Arg Leu Glu Ser Leu Ile Thr         
            180                 185                 190                 

gac acg gat gat gat cgt ctt tca aga caa gtt aag gaa gct cta aag      624
Asp Thr Asp Asp Asp Arg Leu Ser Arg Gln Val Lys Glu Ala Leu Lys         
        195                 200                 205                     

atc cca att agc aag act cta aca agg ttg gga gca aga aag ttc att      672
Ile Pro Ile Ser Lys Thr Leu Thr Arg Leu Gly Ala Arg Lys Phe Ile         
    210                 215                 220                         

tct atg tac aaa gaa gac gac tct cac aat gaa aaa cta ctc aag ttt      720
Ser Met Tyr Lys Glu Asp Asp Ser His Asn Glu Lys Leu Leu Lys Phe         
225                 230                 235                 240         

gcc atg ttg gac ttt aac atg gta caa agg cta cat caa aat gag ctt      768
Ala Met Leu Asp Phe Asn Met Val Gln Arg Leu His Gln Asn Glu Leu         
                245                 250                 255             

agc cat ctt aca aga tgg tgg aag gaa tta gac ttt gca aac aag ctg      816
Ser His Leu Thr Arg Trp Trp Lys Glu Leu Asp Phe Ala Asn Lys Leu         
            260                 265                 270                 

cct ttt gct agg gat aga ctt gtg gag tgc tac ttc tgg att atg gga      864
Pro Phe Ala Arg Asp Arg Leu Val Glu Cys Tyr Phe Trp Ile Met Gly         
        275                 280                 285                     

gtt tat tat gag ccg cgt cac gaa att gcc cga aaa ata cta acc aaa      912
Val Tyr Tyr Glu Pro Arg His Glu Ile Ala Arg Lys Ile Leu Thr Lys         
    290                 295                 300                         

gtc att tac atg gct tct gtc ctc gat gac att tac gac gtc tat gga      960
Val Ile Tyr Met Ala Ser Val Leu Asp Asp Ile Tyr Asp Val Tyr Gly         
305                 310                 315                 320         

aca tta gac gag ctc aca cta ttc act agc ttt gtt cga agg tgg gac     1008
Thr Leu Asp Glu Leu Thr Leu Phe Thr Ser Phe Val Arg Arg Trp Asp         
                325                 330                 335             

att agt ggc att gat gaa ttg cca aca tac atg aga ata tat ttg aga     1056
Ile Ser Gly Ile Asp Glu Leu Pro Thr Tyr Met Arg Ile Tyr Leu Arg         
            340                 345                 350                 

gcc ctt ttc gat gtg tat gtt gaa atg gaa gaa gaa atg gga aaa ata     1104
Ala Leu Phe Asp Val Tyr Val Glu Met Glu Glu Glu Met Gly Lys Ile         
        355                 360                 365                     

ggc aaa tca tac gca atc gaa tat gca aaa gaa gag atg aaa aga ttg     1152
Gly Lys Ser Tyr Ala Ile Glu Tyr Ala Lys Glu Glu Met Lys Arg Leu         
    370                 375                 380                         

3/11

gca gag gtg tac ttt caa gag gca caa tgg ttc ttt agc aag tac aaa     1200
Ala Glu Val Tyr Phe Gln Glu Ala Gln Trp Phe Phe Ser Lys Tyr Lys         
385                 390                 395                 400         



cct aca atg caa gag tat atg aag gtg gct ctc tta tcg tct ggt tat     1248
Pro Thr Met Gln Glu Tyr Met Lys Val Ala Leu Leu Ser Ser Gly Tyr         
                405                 410                 415             

atg atg atg aca atc aat tca tta gct gtt atc aaa gat cca att acc     1296
Met Met Met Thr Ile Asn Ser Leu Ala Val Ile Lys Asp Pro Ile Thr         
            420                 425                 430                 

aag aaa gag ttt gat tgg gtt gtg agc gaa cca cca att cta aag tca     1344
Lys Lys Glu Phe Asp Trp Val Val Ser Glu Pro Pro Ile Leu Lys Ser         
        435                 440                 445                     

tca tca atc att aca aga tta atg gac gac ctt gcg gga tat ggg tct     1392
Ser Ser Ile Ile Thr Arg Leu Met Asp Asp Leu Ala Gly Tyr Gly Ser         
    450                 455                 460                         

gaa gag aaa cac tca gca gtg cat ctg tac atg aat gaa aag ggc gta     1440
Glu Glu Lys His Ser Ala Val His Leu Tyr Met Asn Glu Lys Gly Val         
465                 470                 475                 480         

tcg gag gaa gaa gcc ttt caa gaa ctc cgc aaa caa gtg aaa aac tca     1488
Ser Glu Glu Glu Ala Phe Gln Glu Leu Arg Lys Gln Val Lys Asn Ser         
                485                 490                 495             

tgg aag aat ata aac aag gaa tgt ctg aag cta cga cca gcc tct gtt     1536
Trp Lys Asn Ile Asn Lys Glu Cys Leu Lys Leu Arg Pro Ala Ser Val         
            500                 505                 510                 

cca atc ctt acg acc gtc gtc aat ttc aca cgt gtt ata atc gtg ttg     1584
Pro Ile Leu Thr Thr Val Val Asn Phe Thr Arg Val Ile Ile Val Leu         
        515                 520                 525                     

tat aca gat gaa gat gca tat ggt aat tct aaa act aag act aaa gat     1632
Tyr Thr Asp Glu Asp Ala Tyr Gly Asn Ser Lys Thr Lys Thr Lys Asp         
    530                 535                 540                         

atg atc aaa tcc ata ctc gtt gat ccc gta taa                         1665
Met Ile Lys Ser Ile Leu Val Asp Pro Val                                 
545                 550                                                 


<210>  2
<211>  554
<212>  PRT
<213>  Origanum vulgare

<400>  2

Met Glu Phe Pro Ala Ser Val Ala Ser Leu Ser Ala Asn Thr Val Gly 
1               5                   10                  15      


Ser Asn Asp Val Leu Arg Arg Ser Ile Ala Tyr His Pro Asn Ile Trp 
            20                  25                  30          
4/11

Gly Asp Phe Phe Leu Ala His Thr Ser Glu Phe Met Glu Ile Ser Ile 
        35                  40                  45              


Ala Glu Lys Glu Glu His Glu Arg Leu Lys Glu Glu Ile Lys Lys Leu 
    50                  55                  60                  


Leu Val Gln Thr Glu Tyr Asp Ser Ile Leu Lys Leu Glu Leu Ile Asp 
65                  70                  75                  80  


Ser Ile Gln Arg Leu Gly Val Gly Tyr His Phe Glu Lys Glu Ile Asp 
                85                  90                  95      


Arg Ile Leu Arg Tyr Val His Gln Thr Tyr Pro Ile Tyr Asp Thr Glu 
            100                 105                 110         


Asn Lys Asp Leu Arg Met Leu Ala Leu Arg Phe Arg Leu Leu Arg Gln 
        115                 120                 125             


Gln Gly Phe His Val Pro Phe Asp Val Leu Ser Glu Phe Ile Asp Ala 
    130                 135                 140                 


Glu Gly Asn Leu Thr Glu Ser Ile Ala Tyr Asp Ile Gln Gly Ile Leu 
145                 150                 155                 160 


Ser Leu Tyr Glu Ala Ser Asn Tyr Gly Val Leu Gly Glu Glu Ile Leu 
                165                 170                 175     


Asp Lys Ala Leu Asp Ser Cys Ser Ser Arg Leu Glu Ser Leu Ile Thr 
            180                 185                 190         


Asp Thr Asp Asp Asp Arg Leu Ser Arg Gln Val Lys Glu Ala Leu Lys 
        195                 200                 205             


Ile Pro Ile Ser Lys Thr Leu Thr Arg Leu Gly Ala Arg Lys Phe Ile 
    210                 215                 220                 


Ser Met Tyr Lys Glu Asp Asp Ser His Asn Glu Lys Leu Leu Lys Phe 
225                 230                 235                 240 


Ala Met Leu Asp Phe Asn Met Val Gln Arg Leu His Gln Asn Glu Leu 
                245                 250                 255     


Ser His Leu Thr Arg Trp Trp Lys Glu Leu Asp Phe Ala Asn Lys Leu 
            260                 265                 270         


5/11

Pro Phe Ala Arg Asp Arg Leu Val Glu Cys Tyr Phe Trp Ile Met Gly 
        275                 280                 285             


Val Tyr Tyr Glu Pro Arg His Glu Ile Ala Arg Lys Ile Leu Thr Lys 
    290                 295                 300                 


Val Ile Tyr Met Ala Ser Val Leu Asp Asp Ile Tyr Asp Val Tyr Gly 
305                 310                 315                 320 


Thr Leu Asp Glu Leu Thr Leu Phe Thr Ser Phe Val Arg Arg Trp Asp 
                325                 330                 335     


Ile Ser Gly Ile Asp Glu Leu Pro Thr Tyr Met Arg Ile Tyr Leu Arg 
            340                 345                 350         


Ala Leu Phe Asp Val Tyr Val Glu Met Glu Glu Glu Met Gly Lys Ile 
        355                 360                 365             


Gly Lys Ser Tyr Ala Ile Glu Tyr Ala Lys Glu Glu Met Lys Arg Leu 
    370                 375                 380                 


Ala Glu Val Tyr Phe Gln Glu Ala Gln Trp Phe Phe Ser Lys Tyr Lys 
385                 390                 395                 400 


Pro Thr Met Gln Glu Tyr Met Lys Val Ala Leu Leu Ser Ser Gly Tyr 
                405                 410                 415     


Met Met Met Thr Ile Asn Ser Leu Ala Val Ile Lys Asp Pro Ile Thr 
            420                 425                 430         


Lys Lys Glu Phe Asp Trp Val Val Ser Glu Pro Pro Ile Leu Lys Ser 
        435                 440                 445             


Ser Ser Ile Ile Thr Arg Leu Met Asp Asp Leu Ala Gly Tyr Gly Ser 
    450                 455                 460                 


Glu Glu Lys His Ser Ala Val His Leu Tyr Met Asn Glu Lys Gly Val 
465                 470                 475                 480 


Ser Glu Glu Glu Ala Phe Gln Glu Leu Arg Lys Gln Val Lys Asn Ser 
                485                 490                 495     


Trp Lys Asn Ile Asn Lys Glu Cys Leu Lys Leu Arg Pro Ala Ser Val 
            500                 505                 510         


6/11

Pro Ile Leu Thr Thr Val Val Asn Phe Thr Arg Val Ile Ile Val Leu 
        515                 520                 525             


Tyr Thr Asp Glu Asp Ala Tyr Gly Asn Ser Lys Thr Lys Thr Lys Asp 
    530                 535                 540                 


Met Ile Lys Ser Ile Leu Val Asp Pro Val 
545                 550                 



<210>  3
<211>  1665
<212>  DNA
<213>  Origanum vulgare


<220>
<221>  CDS
<222>  (1)..(1662)

<400>  3
atg gaa ttt ccg gca tcg gtt gct tcc ctt tcg gct aac acc gtc ggg       48
Met Glu Phe Pro Ala Ser Val Ala Ser Leu Ser Ala Asn Thr Val Gly         
1               5                   10                  15              

tcg aac gat gtt ctt cgt cgc tcc gtc gct tac cat ccc aac att tgg       96
Ser Asn Asp Val Leu Arg Arg Ser Val Ala Tyr His Pro Asn Ile Trp         
            20                  25                  30                  

gga gac ttt ttt ctt gcg cat act tca gaa ttt atg gaa atc tcg att      144
Gly Asp Phe Phe Leu Ala His Thr Ser Glu Phe Met Glu Ile Ser Ile         
        35                  40                  45                      

gct gaa aag gaa gag cac gaa tgg cta aaa gag gag atc aag aaa ttg      192
Ala Glu Lys Glu Glu His Glu Trp Leu Lys Glu Glu Ile Lys Lys Leu         
    50                  55                  60                          

ctc gtt caa act gag tat gat tcg ata ctt aaa tta gaa ctc atc gat      240
Leu Val Gln Thr Glu Tyr Asp Ser Ile Leu Lys Leu Glu Leu Ile Asp         
65                  70                  75                  80          

tca atc caa cga ctt gga gtg agt tac cat ttc gaa aaa gaa att gat      288
Ser Ile Gln Arg Leu Gly Val Ser Tyr His Phe Glu Lys Glu Ile Asp         
                85                  90                  95              

aga atc tta cga tat gtt cat caa acc tac cca ata tac gag acc gaa      336
Arg Ile Leu Arg Tyr Val His Gln Thr Tyr Pro Ile Tyr Glu Thr Glu         
            100                 105                 110                 

aac aag gat ctt cgt atg ctt gct cta cgc ttt cgc cta ctt cga caa      384
Asn Lys Asp Leu Arg Met Leu Ala Leu Arg Phe Arg Leu Leu Arg Gln         
        115                 120                 125                     

cat ggt ttc cat gtt cct tgc gat gtg ttt agt gaa ttc ata gat gcc      432
His Gly Phe His Val Pro Cys Asp Val Phe Ser Glu Phe Ile Asp Ala         
    130                 135                 140                         

7/11

gaa gga aat ctc atg gag tca ata gca tac gac att caa ggg ata ttg      480
Glu Gly Asn Leu Met Glu Ser Ile Ala Tyr Asp Ile Gln Gly Ile Leu         
145                 150                 155                 160         

agc tta tat gag gca tca aat tat gga gtg ctc gga gag gaa att ctt      528
Ser Leu Tyr Glu Ala Ser Asn Tyr Gly Val Leu Gly Glu Glu Ile Leu         
                165                 170                 175             

gac aaa gca tta gat tcg tgc tcg tct cat ctt gaa tcg tta atc acg      576
Asp Lys Ala Leu Asp Ser Cys Ser Ser His Leu Glu Ser Leu Ile Thr         
            180                 185                 190                 

gac acg aat gat gat cgt ctt tca aga caa gtt aag gaa gct cta aag      624
Asp Thr Asn Asp Asp Arg Leu Ser Arg Gln Val Lys Glu Ala Leu Lys         
        195                 200                 205                     


atc cca att agc aag act cta aca agg ttg gga gca aga aag ttc att      672
Ile Pro Ile Ser Lys Thr Leu Thr Arg Leu Gly Ala Arg Lys Phe Ile         
    210                 215                 220                         

tct atg tac aaa gaa gac gac tct cac aat gaa aaa cta ctc aag ttt      720
Ser Met Tyr Lys Glu Asp Asp Ser His Asn Glu Lys Leu Leu Lys Phe         
225                 230                 235                 240         

gcc atg ttg gac ttt aac atg gta caa agg cta cat caa aat gag ctt      768
Ala Met Leu Asp Phe Asn Met Val Gln Arg Leu His Gln Asn Glu Leu         
                245                 250                 255             

agc cat ctt aca agt tgg tgg aag gaa tta gac ttt gca aac aag ctg      816
Ser His Leu Thr Ser Trp Trp Lys Glu Leu Asp Phe Ala Asn Lys Leu         
            260                 265                 270                 

cct ttt gct agg gat aga ctt gtg gag tgc tac ttc tgg att atg gga      864
Pro Phe Ala Arg Asp Arg Leu Val Glu Cys Tyr Phe Trp Ile Met Gly         
        275                 280                 285                     

gtt tat ttt gag ccg cgt cac gaa att gcc cga aaa ata cta acc aaa      912
Val Tyr Phe Glu Pro Arg His Glu Ile Ala Arg Lys Ile Leu Thr Lys         
    290                 295                 300                         

gtc att tac atg gct tct gtc ctt gat gac act tac gac gtc tat gga      960
Val Ile Tyr Met Ala Ser Val Leu Asp Asp Thr Tyr Asp Val Tyr Gly         
305                 310                 315                 320         

aca tta gac gag ctt ata cta ttc act agc gtt gtt cga agg tgg gac     1008
Thr Leu Asp Glu Leu Ile Leu Phe Thr Ser Val Val Arg Arg Trp Asp         
                325                 330                 335             

att agt ggc att gat gaa ttg cca aca tac atg aga ata tac ttg aga     1056
Ile Ser Gly Ile Asp Glu Leu Pro Thr Tyr Met Arg Ile Tyr Leu Arg         
            340                 345                 350                 

gcc ctt ttc gat gtg tat gtt gaa atg gaa gaa gaa atg gga aaa ata     1104
Ala Leu Phe Asp Val Tyr Val Glu Met Glu Glu Glu Met Gly Lys Ile         
        355                 360                 365                     

ggc aaa tca tac gca gtc gaa tat gca aaa gaa gag atg aaa aga ttg     1152
Gly Lys Ser Tyr Ala Val Glu Tyr Ala Lys Glu Glu Met Lys Arg Leu         
    370                 375                 380                         
8/11

gca gag gtg tac ttt caa gag gca caa tgg ttc ttt agc aag tac aaa     1200
Ala Glu Val Tyr Phe Gln Glu Ala Gln Trp Phe Phe Ser Lys Tyr Lys         
385                 390                 395                 400         

cct aca atg caa gag tat atg aag gtg gct ctc tta tcg tct ggt tat     1248
Pro Thr Met Gln Glu Tyr Met Lys Val Ala Leu Leu Ser Ser Gly Tyr         
                405                 410                 415             

atg atg atg aca atc aat tca tta gct gtt atc gaa gat cca att acc     1296
Met Met Met Thr Ile Asn Ser Leu Ala Val Ile Glu Asp Pro Ile Thr         
            420                 425                 430                 

aag aaa gag ttt gat tgg gtt gtg agc gaa cca cca att cta aag tca     1344
Lys Lys Glu Phe Asp Trp Val Val Ser Glu Pro Pro Ile Leu Lys Ser         
        435                 440                 445                     



tca tca atc att aca aga tta atg gac gac ctt gcg gga tat ggg tct     1392
Ser Ser Ile Ile Thr Arg Leu Met Asp Asp Leu Ala Gly Tyr Gly Ser         
    450                 455                 460                         

gaa gat aaa tac tca gca gta cat ctg tac atg aac gaa aag ggc gta     1440
Glu Asp Lys Tyr Ser Ala Val His Leu Tyr Met Asn Glu Lys Gly Val         
465                 470                 475                 480         

tcg gag gaa gaa gcc ttt caa gaa ctc cgc aaa caa gtg aaa aac tca     1488
Ser Glu Glu Glu Ala Phe Gln Glu Leu Arg Lys Gln Val Lys Asn Ser         
                485                 490                 495             

tgg aag aat aga aac aag gaa tgt ctg gag cca cga tca gcc tct gtt     1536
Trp Lys Asn Arg Asn Lys Glu Cys Leu Glu Pro Arg Ser Ala Ser Val         
            500                 505                 510                 

cca att ctt acg acc gtc gtc aat ttc aca cgt gtc gta gtc gtg ttg     1584
Pro Ile Leu Thr Thr Val Val Asn Phe Thr Arg Val Val Val Val Leu         
        515                 520                 525                     

tat aca gat gaa gat gca tat ggc aat tcc aaa aat aag act aaa gat     1632
Tyr Thr Asp Glu Asp Ala Tyr Gly Asn Ser Lys Asn Lys Thr Lys Asp         
    530                 535                 540                         

atg atc aaa tcc ata ctc gtt gat ccc gta taa                         1665
Met Ile Lys Ser Ile Leu Val Asp Pro Val                                 
545                 550                                                 


<210>  4
<211>  554
<212>  PRT
<213>  Origanum vulgare

<400>  4

Met Glu Phe Pro Ala Ser Val Ala Ser Leu Ser Ala Asn Thr Val Gly 
1               5                   10                  15      


Ser Asn Asp Val Leu Arg Arg Ser Val Ala Tyr His Pro Asn Ile Trp 
            20                  25                  30          
9/11

Gly Asp Phe Phe Leu Ala His Thr Ser Glu Phe Met Glu Ile Ser Ile 
        35                  40                  45              


Ala Glu Lys Glu Glu His Glu Trp Leu Lys Glu Glu Ile Lys Lys Leu 
    50                  55                  60                  


Leu Val Gln Thr Glu Tyr Asp Ser Ile Leu Lys Leu Glu Leu Ile Asp 
65                  70                  75                  80  


Ser Ile Gln Arg Leu Gly Val Ser Tyr His Phe Glu Lys Glu Ile Asp 
                85                  90                  95      


Arg Ile Leu Arg Tyr Val His Gln Thr Tyr Pro Ile Tyr Glu Thr Glu 
            100                 105                 110         


Asn Lys Asp Leu Arg Met Leu Ala Leu Arg Phe Arg Leu Leu Arg Gln 
        115                 120                 125             



His Gly Phe His Val Pro Cys Asp Val Phe Ser Glu Phe Ile Asp Ala 
    130                 135                 140                 


Glu Gly Asn Leu Met Glu Ser Ile Ala Tyr Asp Ile Gln Gly Ile Leu 
145                 150                 155                 160 


Ser Leu Tyr Glu Ala Ser Asn Tyr Gly Val Leu Gly Glu Glu Ile Leu 
                165                 170                 175     


Asp Lys Ala Leu Asp Ser Cys Ser Ser His Leu Glu Ser Leu Ile Thr 
            180                 185                 190         


Asp Thr Asn Asp Asp Arg Leu Ser Arg Gln Val Lys Glu Ala Leu Lys 
        195                 200                 205             


Ile Pro Ile Ser Lys Thr Leu Thr Arg Leu Gly Ala Arg Lys Phe Ile 
    210                 215                 220                 


Ser Met Tyr Lys Glu Asp Asp Ser His Asn Glu Lys Leu Leu Lys Phe 
225                 230                 235                 240 


Ala Met Leu Asp Phe Asn Met Val Gln Arg Leu His Gln Asn Glu Leu 
                245                 250                 255     


Ser His Leu Thr Ser Trp Trp Lys Glu Leu Asp Phe Ala Asn Lys Leu 
            260                 265                 270         

10/11

Pro Phe Ala Arg Asp Arg Leu Val Glu Cys Tyr Phe Trp Ile Met Gly 
        275                 280                 285             


Val Tyr Phe Glu Pro Arg His Glu Ile Ala Arg Lys Ile Leu Thr Lys 
    290                 295                 300                 


Val Ile Tyr Met Ala Ser Val Leu Asp Asp Thr Tyr Asp Val Tyr Gly 
305                 310                 315                 320 


Thr Leu Asp Glu Leu Ile Leu Phe Thr Ser Val Val Arg Arg Trp Asp 
                325                 330                 335     


Ile Ser Gly Ile Asp Glu Leu Pro Thr Tyr Met Arg Ile Tyr Leu Arg 
            340                 345                 350         



Ala Leu Phe Asp Val Tyr Val Glu Met Glu Glu Glu Met Gly Lys Ile 
        355                 360                 365             


Gly Lys Ser Tyr Ala Val Glu Tyr Ala Lys Glu Glu Met Lys Arg Leu 
    370                 375                 380                 


Ala Glu Val Tyr Phe Gln Glu Ala Gln Trp Phe Phe Ser Lys Tyr Lys 
385                 390                 395                 400 


Pro Thr Met Gln Glu Tyr Met Lys Val Ala Leu Leu Ser Ser Gly Tyr 
                405                 410                 415     


Met Met Met Thr Ile Asn Ser Leu Ala Val Ile Glu Asp Pro Ile Thr 
            420                 425                 430         


Lys Lys Glu Phe Asp Trp Val Val Ser Glu Pro Pro Ile Leu Lys Ser 
        435                 440                 445             


Ser Ser Ile Ile Thr Arg Leu Met Asp Asp Leu Ala Gly Tyr Gly Ser 
    450                 455                 460                 


Glu Asp Lys Tyr Ser Ala Val His Leu Tyr Met Asn Glu Lys Gly Val 
465                 470                 475                 480 


Ser Glu Glu Glu Ala Phe Gln Glu Leu Arg Lys Gln Val Lys Asn Ser 
                485                 490                 495     


Trp Lys Asn Arg Asn Lys Glu Cys Leu Glu Pro Arg Ser Ala Ser Val 
            500                 505                 510         

11/11

Pro Ile Leu Thr Thr Val Val Asn Phe Thr Arg Val Val Val Val Leu 
        515                 520                 525             


Tyr Thr Asp Glu Asp Ala Tyr Gly Asn Ser Lys Asn Lys Thr Lys Asp 
    530                 535                 540                 


Met Ile Lys Ser Ile Leu Val Asp Pro Val 
545                 550                 



















