                         SEQUENCE LISTING

<110>  C4 Therapeutics
 
<120>  Method to Induce Targeted Protein Degradation Through 
       Bifunctional Compounds That Selectively Bind to a Mutant E3 
       Ubiquitin Ligase

<130>  16010-020WO1

<150>  US 62/401,303
<151>  2016-09-29

<160>  10    

<170>  PatentIn version 3.5

<210>  1
<211>  442
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Gly Glu Gly Asp Gln Gln Asp Ala Ala His Asn Met Gly Asn 
1               5                   10                  15      


His Leu Pro Leu Leu Pro Ala Glu Ser Glu Glu Glu Asp Glu Met Glu 
            20                  25                  30          


Val Glu Asp Gln Asp Ser Lys Glu Ala Lys Lys Pro Asn Ile Ile Asn 
        35                  40                  45              


Phe Asp Thr Ser Leu Pro Thr Ser His Thr Tyr Leu Gly Ala Asp Met 
    50                  55                  60                  


Glu Glu Phe His Gly Arg Thr Leu His Asp Asp Asp Ser Cys Gln Val 
65                  70                  75                  80  


Ile Pro Val Leu Pro Gln Val Met Met Ile Leu Ile Pro Gly Gln Thr 
                85                  90                  95      


Leu Pro Leu Gln Leu Phe His Pro Gln Glu Val Ser Met Val Arg Asn 
            100                 105                 110         


Leu Ile Gln Lys Asp Arg Thr Phe Ala Val Leu Ala Tyr Ser Asn Val 
        115                 120                 125             


Gln Glu Arg Glu Ala Gln Phe Gly Thr Thr Ala Glu Ile Tyr Ala Tyr 
    130                 135                 140                 


Arg Glu Glu Gln Asp Phe Gly Ile Glu Ile Val Lys Val Lys Ala Ile 
145                 150                 155                 160 


Gly Arg Gln Arg Phe Lys Val Leu Glu Leu Arg Thr Gln Ser Asp Gly 
                165                 170                 175     


Ile Gln Gln Ala Lys Val Gln Ile Leu Pro Glu Cys Val Leu Pro Ser 
            180                 185                 190         


Thr Met Ser Ala Val Gln Leu Glu Ser Leu Asn Lys Cys Gln Ile Phe 
        195                 200                 205             


Pro Ser Lys Pro Val Ser Arg Glu Asp Gln Cys Ser Tyr Lys Trp Trp 
    210                 215                 220                 


Gln Lys Tyr Gln Lys Arg Lys Phe His Cys Ala Asn Leu Thr Ser Trp 
225                 230                 235                 240 


Pro Arg Trp Leu Tyr Ser Leu Tyr Asp Ala Glu Thr Leu Met Asp Arg 
                245                 250                 255     


Ile Lys Lys Gln Leu Arg Glu Trp Asp Glu Asn Leu Lys Asp Asp Ser 
            260                 265                 270         


Leu Pro Ser Asn Pro Ile Asp Phe Ser Tyr Arg Val Ala Ala Cys Leu 
        275                 280                 285             


Pro Ile Asp Asp Val Leu Arg Ile Gln Leu Leu Lys Ile Gly Ser Ala 
    290                 295                 300                 


Ile Gln Arg Leu Arg Cys Glu Leu Asp Ile Met Asn Lys Cys Thr Ser 
305                 310                 315                 320 


Leu Cys Cys Lys Gln Cys Gln Glu Thr Glu Ile Thr Thr Lys Asn Glu 
                325                 330                 335     


Ile Phe Ser Leu Ser Leu Cys Gly Pro Met Ala Ala Tyr Val Asn Pro 
            340                 345                 350         


His Gly Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Cys Asn Leu 
        355                 360                 365             


Asn Leu Ile Gly Arg Pro Ser Thr Glu His Ser Trp Phe Pro Gly Tyr 
    370                 375                 380                 


Ala Trp Thr Val Ala Gln Cys Lys Ile Cys Ala Ser His Ile Gly Trp 
385                 390                 395                 400 


Lys Phe Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe Trp Gly 
                405                 410                 415     


Leu Thr Arg Ser Ala Leu Leu Pro Thr Ile Pro Asp Thr Glu Asp Glu 
            420                 425                 430         


Ile Ser Pro Asp Lys Val Ile Leu Cys Leu 
        435                 440         


<210>  2
<211>  441
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Ala Gly Glu Gly Asp Gln Gln Asp Ala Ala His Asn Met Gly Asn 
1               5                   10                  15      


His Leu Pro Leu Leu Pro Glu Ser Glu Glu Glu Asp Glu Met Glu Val 
            20                  25                  30          


Glu Asp Gln Asp Ser Lys Glu Ala Lys Lys Pro Asn Ile Ile Asn Phe 
        35                  40                  45              


Asp Thr Ser Leu Pro Thr Ser His Thr Tyr Leu Gly Ala Asp Met Glu 
    50                  55                  60                  


Glu Phe His Gly Arg Thr Leu His Asp Asp Asp Ser Cys Gln Val Ile 
65                  70                  75                  80  


Pro Val Leu Pro Gln Val Met Met Ile Leu Ile Pro Gly Gln Thr Leu 
                85                  90                  95      


Pro Leu Gln Leu Phe His Pro Gln Glu Val Ser Met Val Arg Asn Leu 
            100                 105                 110         


Ile Gln Lys Asp Arg Thr Phe Ala Val Leu Ala Tyr Ser Asn Val Gln 
        115                 120                 125             


Glu Arg Glu Ala Gln Phe Gly Thr Thr Ala Glu Ile Tyr Ala Tyr Arg 
    130                 135                 140                 


Glu Glu Gln Asp Phe Gly Ile Glu Ile Val Lys Val Lys Ala Ile Gly 
145                 150                 155                 160 


Arg Gln Arg Phe Lys Val Leu Glu Leu Arg Thr Gln Ser Asp Gly Ile 
                165                 170                 175     


Gln Gln Ala Lys Val Gln Ile Leu Pro Glu Cys Val Leu Pro Ser Thr 
            180                 185                 190         


Met Ser Ala Val Gln Leu Glu Ser Leu Asn Lys Cys Gln Ile Phe Pro 
        195                 200                 205             


Ser Lys Pro Val Ser Arg Glu Asp Gln Cys Ser Tyr Lys Trp Trp Gln 
    210                 215                 220                 


Lys Tyr Gln Lys Arg Lys Phe His Cys Ala Asn Leu Thr Ser Trp Pro 
225                 230                 235                 240 


Arg Trp Leu Tyr Ser Leu Tyr Asp Ala Glu Thr Leu Met Asp Arg Ile 
                245                 250                 255     


Lys Lys Gln Leu Arg Glu Trp Asp Glu Asn Leu Lys Asp Asp Ser Leu 
            260                 265                 270         


Pro Ser Asn Pro Ile Asp Phe Ser Tyr Arg Val Ala Ala Cys Leu Pro 
        275                 280                 285             


Ile Asp Asp Val Leu Arg Ile Gln Leu Leu Lys Ile Gly Ser Ala Ile 
    290                 295                 300                 


Gln Arg Leu Arg Cys Glu Leu Asp Ile Met Asn Lys Cys Thr Ser Leu 
305                 310                 315                 320 


Cys Cys Lys Gln Cys Gln Glu Thr Glu Ile Thr Thr Lys Asn Glu Ile 
                325                 330                 335     


Phe Ser Leu Ser Leu Cys Gly Pro Met Ala Ala Tyr Val Asn Pro His 
            340                 345                 350         


Gly Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Cys Asn Leu Asn 
        355                 360                 365             


Leu Ile Gly Arg Pro Ser Thr Glu His Ser Trp Phe Pro Gly Tyr Ala 
    370                 375                 380                 


Trp Thr Val Ala Gln Cys Lys Ile Cys Ala Ser His Ile Gly Trp Lys 
385                 390                 395                 400 


Phe Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe Trp Gly Leu 
                405                 410                 415     


Thr Arg Ser Ala Leu Leu Pro Thr Ile Pro Asp Thr Glu Asp Glu Ile 
            420                 425                 430         


Ser Pro Asp Lys Val Ile Leu Cys Leu 
        435                 440     


<210>  3
<211>  444
<212>  PRT
<213>  Mus musculus

<400>  3

Met Ala Gly Glu Gly Asp Gln Gln Asp Ala Ala His Asn Met Gly Asn 
1               5                   10                  15      


His Leu Pro Leu Leu Pro Asp Ser Glu Asp Glu Asp Asp Glu Ile Glu 
            20                  25                  30          


Met Glu Val Glu Asp Gln Asp Ser Lys Glu Ala Arg Lys Pro Asn Ile 
        35                  40                  45              


Ile Asn Phe Asp Thr Ser Leu Pro Thr Ser His Thr Tyr Leu Gly Ala 
    50                  55                  60                  


Asp Met Glu Glu Phe His Gly Arg Thr Leu His Asp Asp Asp Ser Cys 
65                  70                  75                  80  


Gln Val Ile Pro Val Leu Pro Glu Val Leu Met Ile Leu Ile Pro Gly 
                85                  90                  95      


Gln Thr Leu Pro Leu Gln Leu Ser His Pro Gln Glu Val Ser Met Val 
            100                 105                 110         


Arg Asn Leu Ile Gln Lys Asp Arg Thr Phe Ala Val Leu Ala Tyr Ser 
        115                 120                 125             


Asn Val Gln Glu Arg Glu Ala Gln Phe Gly Thr Thr Ala Glu Ile Tyr 
    130                 135                 140                 


Ala Tyr Arg Glu Glu Gln Glu Phe Gly Ile Glu Val Val Lys Val Lys 
145                 150                 155                 160 


Ala Ile Gly Arg Gln Arg Phe Lys Val Leu Glu Leu Arg Thr Gln Ser 
                165                 170                 175     


Asp Gly Ile Gln Gln Ala Lys Val Gln Ile Leu Pro Glu Cys Val Leu 
            180                 185                 190         


Pro Ser Thr Met Ser Ala Val Gln Leu Glu Ser Leu Asn Lys Cys Gln 
        195                 200                 205             


Val Phe Pro Ser Lys Pro Ile Ser Trp Glu Asp Gln Tyr Ser Cys Lys 
    210                 215                 220                 


Trp Trp Gln Lys Tyr Gln Lys Arg Lys Phe His Cys Ala Asn Leu Thr 
225                 230                 235                 240 


Ser Trp Pro Arg Trp Leu Tyr Ser Leu Tyr Asp Ala Glu Thr Leu Met 
                245                 250                 255     


Asp Arg Ile Lys Lys Gln Leu Arg Glu Trp Asp Glu Asn Leu Lys Asp 
            260                 265                 270         


Asp Ser Leu Pro Glu Asn Pro Ile Asp Phe Ser Tyr Arg Val Ala Ala 
        275                 280                 285             


Cys Leu Pro Ile Asp Asp Val Leu Arg Ile Gln Leu Leu Lys Ile Gly 
    290                 295                 300                 


Ser Ala Ile Gln Arg Leu Arg Cys Glu Leu Asp Ile Met Asn Lys Cys 
305                 310                 315                 320 


Thr Ser Leu Cys Cys Lys Gln Cys Gln Glu Thr Glu Ile Thr Thr Lys 
                325                 330                 335     


Asn Glu Ile Phe Ser Leu Ser Leu Cys Gly Pro Met Ala Ala Tyr Val 
            340                 345                 350         


Asn Pro His Gly Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Ser 
        355                 360                 365             


Asn Leu Asn Leu Ile Gly Arg Pro Ser Thr Val His Ser Trp Phe Pro 
    370                 375                 380                 


Gly Tyr Ala Trp Thr Ile Ala Gln Cys Lys Ile Cys Ala Ser His Ile 
385                 390                 395                 400 


Gly Trp Lys Phe Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe 
                405                 410                 415     


Trp Gly Leu Thr Arg Ser Ala Leu Leu Pro Thr Ile Pro Glu Thr Glu 
            420                 425                 430         


Asp Glu Ile Ser Pro Asp Lys Val Ile Leu Cys Leu 
        435                 440                 


<210>  4
<211>  445
<212>  PRT
<213>  Mus musculus

<400>  4

Met Ala Gly Glu Gly Asp Gln Gln Asp Ala Ala His Asn Met Gly Asn 
1               5                   10                  15      


His Leu Pro Leu Leu Pro Ala Asp Ser Glu Asp Glu Asp Asp Glu Ile 
            20                  25                  30          


Glu Met Glu Val Glu Asp Gln Asp Ser Lys Glu Ala Arg Lys Pro Asn 
        35                  40                  45              


Ile Ile Asn Phe Asp Thr Ser Leu Pro Thr Ser His Thr Tyr Leu Gly 
    50                  55                  60                  


Ala Asp Met Glu Glu Phe His Gly Arg Thr Leu His Asp Asp Asp Ser 
65                  70                  75                  80  


Cys Gln Val Ile Pro Val Leu Pro Glu Val Leu Met Ile Leu Ile Pro 
                85                  90                  95      


Gly Gln Thr Leu Pro Leu Gln Leu Ser His Pro Gln Glu Val Ser Met 
            100                 105                 110         


Val Arg Asn Leu Ile Gln Lys Asp Arg Thr Phe Ala Val Leu Ala Tyr 
        115                 120                 125             


Ser Asn Val Gln Glu Arg Glu Ala Gln Phe Gly Thr Thr Ala Glu Ile 
    130                 135                 140                 


Tyr Ala Tyr Arg Glu Glu Gln Glu Phe Gly Ile Glu Val Val Lys Val 
145                 150                 155                 160 


Lys Ala Ile Gly Arg Gln Arg Phe Lys Val Leu Glu Leu Arg Thr Gln 
                165                 170                 175     


Ser Asp Gly Ile Gln Gln Ala Lys Val Gln Ile Leu Pro Glu Cys Val 
            180                 185                 190         


Leu Pro Ser Thr Met Ser Ala Val Gln Leu Glu Ser Leu Asn Lys Cys 
        195                 200                 205             


Gln Val Phe Pro Ser Lys Pro Ile Ser Trp Glu Asp Gln Tyr Ser Cys 
    210                 215                 220                 


Lys Trp Trp Gln Lys Tyr Gln Lys Arg Lys Phe His Cys Ala Asn Leu 
225                 230                 235                 240 


Thr Ser Trp Pro Arg Trp Leu Tyr Ser Leu Tyr Asp Ala Glu Thr Leu 
                245                 250                 255     


Met Asp Arg Ile Lys Lys Gln Leu Arg Glu Trp Asp Glu Asn Leu Lys 
            260                 265                 270         


Asp Asp Ser Leu Pro Glu Asn Pro Ile Asp Phe Ser Tyr Arg Val Ala 
        275                 280                 285             


Ala Cys Leu Pro Ile Asp Asp Val Leu Arg Ile Gln Leu Leu Lys Ile 
    290                 295                 300                 


Gly Ser Ala Ile Gln Arg Leu Arg Cys Glu Leu Asp Ile Met Asn Lys 
305                 310                 315                 320 


Cys Thr Ser Leu Cys Cys Lys Gln Cys Gln Glu Thr Glu Ile Thr Thr 
                325                 330                 335     


Lys Asn Glu Ile Phe Ser Leu Ser Leu Cys Gly Pro Met Ala Ala Tyr 
            340                 345                 350         


Val Asn Pro His Gly Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala 
        355                 360                 365             


Ser Asn Leu Asn Leu Ile Gly Arg Pro Ser Thr Val His Ser Trp Phe 
    370                 375                 380                 


Pro Gly Tyr Ala Trp Thr Ile Ala Gln Cys Lys Ile Cys Ala Ser His 
385                 390                 395                 400 


Ile Gly Trp Lys Phe Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys 
                405                 410                 415     


Phe Trp Gly Leu Thr Arg Ser Ala Leu Leu Pro Thr Ile Pro Glu Thr 
            420                 425                 430         


Glu Asp Glu Ile Ser Pro Asp Lys Val Ile Leu Cys Leu 
        435                 440                 445 


<210>  5
<211>  445
<212>  PRT
<213>  Rattus norvegicus

<400>  5

Met Ala Gly Glu Gly Asp His Gln Asp Ala Ala His Asn Met Gly Asn 
1               5                   10                  15      


His Leu Pro Leu Leu Pro Ala Asp Ser Glu Asp Glu Asp Asp Glu Ile 
            20                  25                  30          


Glu Met Glu Val Glu Asp Gln Asp Ser Lys Glu Ala Arg Lys Pro Asn 
        35                  40                  45              


Ile Ile Asn Phe Asp Thr Ser Leu Pro Thr Ser His Thr Tyr Leu Gly 
    50                  55                  60                  


Ala Asp Met Glu Glu Phe His Gly Arg Thr Leu His Asp Asp Asp Ser 
65                  70                  75                  80  


Cys Gln Val Ile Pro Val Leu Pro Glu Val Met Met Ile Leu Ile Pro 
                85                  90                  95      


Gly Gln Thr Leu Pro Leu Gln Leu Ser His Pro Gln Glu Val Ser Met 
            100                 105                 110         


Val Arg Asn Leu Ile Gln Lys Asp Arg Thr Phe Ala Val Leu Ala Tyr 
        115                 120                 125             


Ser Asn Val Gln Glu Arg Glu Ala Gln Phe Gly Thr Thr Ala Glu Ile 
    130                 135                 140                 


Tyr Ala Tyr Arg Glu Glu Gln Glu Phe Gly Ile Glu Val Val Lys Val 
145                 150                 155                 160 


Lys Ala Ile Gly Arg Gln Arg Phe Lys Val Leu Glu Leu Arg Thr Gln 
                165                 170                 175     


Ser Asp Gly Ile Gln Gln Ala Lys Val Gln Ile Leu Pro Glu Cys Val 
            180                 185                 190         


Leu Pro Ser Thr Met Ser Ala Val Gln Leu Glu Ser Leu Asn Lys Cys 
        195                 200                 205             


Gln Ile Phe Pro Ser Lys Pro Ile Ser Trp Glu Asp Gln Tyr Ser Cys 
    210                 215                 220                 


Lys Trp Trp Gln Lys Tyr Gln Lys Arg Lys Phe His Cys Ala Asn Leu 
225                 230                 235                 240 


Thr Ser Trp Pro Arg Trp Leu Tyr Ser Leu Tyr Asp Ala Glu Thr Leu 
                245                 250                 255     


Met Asp Arg Ile Lys Lys Gln Leu Arg Glu Trp Asp Glu Asn Leu Lys 
            260                 265                 270         


Glu Asp Ser Leu Pro Ala Asn Pro Ile Asp Phe Ser Tyr Arg Val Ala 
        275                 280                 285             


Ala Cys Leu Pro Ile Asp Asp Val Leu Arg Ile Gln Leu Leu Lys Ile 
    290                 295                 300                 


Gly Ser Ala Ile Gln Arg Leu Arg Cys Glu Leu Asp Ile Met Asn Lys 
305                 310                 315                 320 


Cys Thr Ser Leu Cys Cys Lys Gln Cys Gln Glu Thr Glu Ile Thr Thr 
                325                 330                 335     


Lys Asn Glu Ile Phe Ser Leu Ser Leu Cys Gly Pro Met Ala Ala Tyr 
            340                 345                 350         


Val Asn Pro His Gly Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala 
        355                 360                 365             


Ser Asn Leu Asn Leu Ile Gly Arg Pro Ser Thr Val His Ser Trp Phe 
    370                 375                 380                 


Pro Gly Tyr Ala Trp Thr Ile Ala Gln Cys Lys Ile Cys Ala Ser His 
385                 390                 395                 400 


Ile Gly Trp Lys Phe Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys 
                405                 410                 415     


Phe Trp Gly Leu Thr Arg Ser Ala Leu Leu Pro Thr Ile Pro Glu Thr 
            420                 425                 430         


Glu Asp Glu Ile Ser Pro Asp Lys Val Ile Leu Cys Leu 
        435                 440                 445 


<210>  6
<211>  444
<212>  PRT
<213>  Bos taurus

<400>  6

Met Ala Gly Glu Gly Asp Pro Glu Asp Ala Ala His Asn Met Gly Asn 
1               5                   10                  15      


His Leu Pro Leu Leu Pro Ala Glu Glu Glu Glu Glu Asp Glu Ile Glu 
            20                  25                  30          


Met Glu Val Glu Asp Gln Asp Asn Lys Glu Pro Lys Lys Pro Asn Ile 
        35                  40                  45              


Ile Asn Phe Asp Thr Ser Leu Pro Thr Ser His Thr Tyr Leu Gly Ser 
    50                  55                  60                  


Asp Met Glu Glu Phe His Gly Arg Thr Leu His Asp Asp Asp Ser Cys 
65                  70                  75                  80  


Pro Val Ile Pro Val Leu Pro Gln Val Val Met Thr Leu Ile Pro Gly 
                85                  90                  95      


Gln Thr Leu Pro Leu Gln Leu Phe Ser Pro Gln Glu Val Ser Met Val 
            100                 105                 110         


Arg Asn Leu Ile Gln Lys Asp Arg Thr Phe Ala Val Leu Ala Tyr Ser 
        115                 120                 125             


Asn Val Gln Glu Arg Glu Ala Gln Phe Gly Thr Thr Ala Glu Ile Tyr 
    130                 135                 140                 


Ala Tyr Arg Glu Glu Gln Asp Phe Gly Ile Glu Val Val Lys Val Lys 
145                 150                 155                 160 


Ala Ile Gly Arg Gln Arg Phe Lys Val Leu Glu Ile Arg Thr Gln Ser 
                165                 170                 175     


Asp Gly Ile Gln Gln Ala Lys Val Gln Ile Leu Pro Glu Cys Val Leu 
            180                 185                 190         


Pro Ser Thr Met Ser Ala Val Gln Leu Glu Ser Leu Asn Lys Cys Arg 
        195                 200                 205             


Ile Phe Pro Ser Lys Pro Val Ser Trp Glu Asp Gln Cys Ser Tyr Lys 
    210                 215                 220                 


Trp Trp Gln Lys Tyr Gln Lys Arg Lys Phe His Cys Ala Asn Leu Thr 
225                 230                 235                 240 


Ser Trp Pro Arg Trp Leu Tyr Ser Leu Tyr Asp Ala Glu Thr Leu Met 
                245                 250                 255     


Asp Arg Ile Lys Lys Gln Leu Arg Glu Trp Asp Glu Asn Leu Lys Glu 
            260                 265                 270         


Asp Ser Leu Pro Ser Asn Pro Ile Asp Phe Ser Tyr Arg Val Ala Ala 
        275                 280                 285             


Cys Leu Pro Ile Asp Asp Val Leu Arg Ile Gln Leu Leu Lys Ile Gly 
    290                 295                 300                 


Ser Ala Ile Gln Arg Leu Arg Cys Glu Leu Asp Ile Met Asn Lys Cys 
305                 310                 315                 320 


Thr Ser Leu Cys Cys Lys Gln Cys Gln Glu Thr Glu Ile Thr Thr Lys 
                325                 330                 335     


Asn Glu Ile Phe Ser Leu Ser Leu Cys Gly Pro Met Ala Ala Tyr Val 
            340                 345                 350         


Asn Pro His Gly Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Ser 
        355                 360                 365             


Asn Leu Asn Leu Ile Gly Arg Pro Ser Thr Asp His Ser Trp Phe Pro 
    370                 375                 380                 


Gly Tyr Ala Trp Thr Ile Ala Gln Cys Arg Ile Cys Ala Ser His Ile 
385                 390                 395                 400 


Gly Trp Lys Phe Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe 
                405                 410                 415     


Trp Gly Leu Thr Arg Ser Ala Leu Leu Pro Thr Ile Pro Asp Thr Glu 
            420                 425                 430         


Asp Asp Ile Ser Pro Asp Lys Val Ile Leu Cys Leu 
        435                 440                 


<210>  7
<211>  431
<212>  PRT
<213>  Danio rerio

<400>  7

Met Gly Asn Gln Leu Gln Leu Leu Pro Glu Asn Glu Glu Glu Glu Glu 
1               5                   10                  15      


Asp Asp Met Glu Thr Glu Asp Arg Asp Gly Glu Asp Val Glu Lys Pro 
            20                  25                  30          


Ser Ile Ile Asn Phe Asp Thr Ser Leu Pro Thr Ser His Ala Tyr Leu 
        35                  40                  45              


Gly Ser Asp Met Glu Glu Phe His Gly Arg Thr Leu His Asp Glu Asp 
    50                  55                  60                  


Ser Val Gln Asn Leu Pro Val Leu Pro His Val Ala Leu Ile Leu Ile 
65                  70                  75                  80  


Pro Gly Gln Thr Leu Pro Leu Gln Leu Phe Arg Pro Gln Glu Val Ser 
                85                  90                  95      


Met Phe Arg Asn Leu Val Ser Gln Asp Arg Thr Phe Ala Val Leu Ala 
            100                 105                 110         


His Ser Pro Asp Pro Ser Gly Thr Glu Thr Lys Ala Glu Phe Gly Thr 
        115                 120                 125             


Thr Ala Glu Ile Tyr Ala Phe Arg Glu Glu Gln Glu Tyr Gly Ile Glu 
    130                 135                 140                 


Thr Val Lys Ile Lys Ala Val Gly Arg Gln Arg Phe Arg Val His Asp 
145                 150                 155                 160 


Ile Arg Thr Gln Ala Asp Gly Ile Arg Gln Ala Lys Val Gln Ile Leu 
                165                 170                 175     


Pro Glu Arg Ile Leu Pro Asp Pro Leu Cys Ala Leu Gln Phe Leu Pro 
            180                 185                 190         


Arg Leu His Thr His Ser Pro Gln Thr Lys His Thr Gln Thr Thr Pro 
        195                 200                 205             


Pro Gln Lys Arg Cys Ser Gln Asn Tyr Arg Gln Lys Lys Leu His Cys 
    210                 215                 220                 


Ala Ser Met Thr Ser Trp Pro Pro Trp Val Tyr Ser Leu Tyr Asp Ser 
225                 230                 235                 240 


Lys Thr Leu Met Ser Arg Val Lys Lys Gln Leu His Glu Trp Asp Glu 
                245                 250                 255     


Asn Leu Lys Asp Glu Ser Leu Pro Thr Asn Pro Thr Asp Phe Ser Tyr 
            260                 265                 270         


Arg Val Ala Ala Cys Leu Pro Ile Asp Asp Ala Leu Arg Leu Gln Leu 
        275                 280                 285             


Leu Lys Ile Gly Ser Ala Ile Gln Arg Leu Arg Cys Glu Leu Asp Ile 
    290                 295                 300                 


Met Asp Arg Cys Thr Ser Leu Cys Cys Lys Gln Cys Gln Asp Thr Glu 
305                 310                 315                 320 


Ile Thr Ser Lys Asn Glu Ile Phe Ser Leu Ser Leu Tyr Gly Pro Met 
                325                 330                 335     


Ala Ala Tyr Val Asn Pro His Gly Tyr Val His Glu Thr Leu Thr Val 
            340                 345                 350         


Tyr Lys Ala Ser Asn Leu Asn Leu Ile Gly Arg Pro Ser Thr Leu His 
        355                 360                 365             


Ser Trp Phe Pro Gly Tyr Ala Trp Thr Ile Ala Gln Cys Arg Thr Cys 
    370                 375                 380                 


Ser Ser His Met Gly Trp Lys Phe Ser Ala Val Lys Lys Asp Leu Ser 
385                 390                 395                 400 


Pro Pro Arg Phe Trp Gly Leu Thr Arg Ser Ala Leu Leu Pro Thr Ile 
                405                 410                 415     


Pro Gln Gly Glu Glu Gly Val Glu Gly Ser Arg Leu Leu Cys Leu 
            420                 425                 430     


<210>  8
<211>  1368
<212>  PRT
<213>  Streptococcus pyogenes

<400>  8

Met Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 
                165                 170                 175     


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 
        195                 200                 205             


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 
                245                 250                 255     


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 
545                 550                 555                 560 


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


<210>  9
<211>  200
<212>  DNA
<213>  synthetic

<400>  9
tacagaaatg tttccttagc tgatatcttt ccttaatttc ttaggtatgc ctggactgtt       60

gcccagtgta agatctgtgc aagccatatt ggatggaagg ctactgccac caaaaaagac      120

atgtcacctc aaaaattttg gggcttaacg cgatctgctc tgttgcccac gatcccagac      180

actgaagatg aaataagtcc                                                  200


<210>  10
<211>  20
<212>  DNA
<213>  synthetic

<400>  10
ccatattgga tggaagttta                                                   20


