                         SEQUENCE LISTING

<110>  Yeda Research And Development Co. Ltd.
       FLEISHMAN, Sarel
       GOLDENZWEIG, Adi
       TAWFIK, Dan S.
 
<120>  STABLE PROTEINS AND METHODS FOR DESIGNING SAME

<130>  65005

<150>  US 62/197,598
<151>  2015-07-28

<150>  US 62/337,992
<151>  2016-05-18

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  542
<212>  PRT
<213>  Homo sapiens

<400>  1

Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Val Arg Gly Gly Arg Leu 
1               5                   10                  15      


Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pro Val Ser Ala Phe Leu 
            20                  25                  30          


Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pro Arg Arg Phe Leu Pro 
        35                  40                  45              


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


Gln Ser Val Cys Tyr Gln Tyr Val Asp Thr Leu Tyr Pro Gly Phe Glu 
65                  70                  75                  80  


Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Leu Ser Glu Asp Cys Leu 
                85                  90                  95      


Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pro Thr Ser Pro Thr Pro 
            100                 105                 110         


Val Leu Val Trp Ile Tyr Gly Gly Gly Phe Tyr Ser Gly Ala Ser Ser 
        115                 120                 125             


Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gln Ala Glu Arg Thr Val 
    130                 135                 140                 


Leu Val Ser Met Asn Tyr Arg Val Gly Ala Phe Gly Phe Leu Ala Leu 
145                 150                 155                 160 


Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gly Leu Leu Asp Gln Arg 
                165                 170                 175     


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


Pro Thr Ser Val Thr Leu Phe Gly Glu Ser Ala Gly Ala Ala Ser Val 
        195                 200                 205             


Gly Met His Leu Leu Ser Pro Pro Ser Arg Gly Leu Phe His Arg Ala 
    210                 215                 220                 


Val Leu Gln Ser Gly Ala Pro Asn Gly Pro Trp Ala Thr Val Gly Met 
225                 230                 235                 240 


Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Ala His Leu Val Gly Cys 
                245                 250                 255     


Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Glu Leu Val Ala Cys Leu 
            260                 265                 270         


Arg Thr Arg Pro Ala Gln Val Leu Val Asn His Glu Trp His Val Leu 
        275                 280                 285             


Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Val Pro Val Val Asp Gly 
    290                 295                 300                 


Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Ile Asn Ala Gly Asp Phe 
305                 310                 315                 320 


His Gly Leu Gln Val Leu Val Gly Val Val Lys Asp Glu Gly Ser Tyr 
                325                 330                 335     


Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Glu Ser Leu 
            340                 345                 350         


Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Arg Val Gly Val Pro Gln 
        355                 360                 365             


Val Ser Asp Leu Ala Ala Glu Ala Val Val Leu His Tyr Thr Asp Trp 
    370                 375                 380                 


Leu His Pro Glu Asp Pro Ala Arg Leu Arg Glu Ala Leu Ser Asp Val 
385                 390                 395                 400 


Val Gly Asp His Asn Val Val Cys Pro Val Ala Gln Leu Ala Gly Arg 
                405                 410                 415     


Leu Ala Ala Gln Gly Ala Arg Val Tyr Ala Tyr Val Phe Glu His Arg 
            420                 425                 430         


Ala Ser Thr Leu Ser Trp Pro Leu Trp Met Gly Val Pro His Gly Tyr 
        435                 440                 445             


Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu Asp Pro Ser Arg Asn Tyr 
    450                 455                 460                 


Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Leu Met Arg Tyr Trp Ala 
465                 470                 475                 480 


Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pro Arg Asp Pro Lys Ala 
                485                 490                 495     


Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gln Gln Tyr Val Ser Leu 
            500                 505                 510         


Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Leu Arg Ala Gln Ala Cys 
        515                 520                 525             


Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Leu Ser Ala Thr 
    530                 535                 540         


<210>  2
<211>  544
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding RhAChE_m0p9

<400>  2

Met Glu Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Thr Arg Gly Gly 
1               5                   10                  15      


Arg Leu Arg Gly Ile Arg Leu Met Thr Pro Gly Gly Pro Val Ser Ala 
            20                  25                  30          


Phe Leu Gly Ile Pro Phe Ala Glu Pro Pro Val Gly Pro Arg Arg Phe 
        35                  40                  45              


Arg Pro Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Trp Asp Ala Thr 
    50                  55                  60                  


Thr Phe Gln Asn Val Cys Tyr Gln Tyr Val Asp Thr Leu Tyr Pro Gly 
65                  70                  75                  80  


Phe Glu Gly Thr Glu Met Trp Asn Pro Asn Arg Asn Leu Ser Glu Asp 
                85                  90                  95      


Cys Leu Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pro Lys Asn Pro 
            100                 105                 110         


Ala Pro Val Met Val Trp Ile Tyr Gly Gly Gly Phe Tyr Ser Gly Ser 
        115                 120                 125             


Ser Ser Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Arg Thr Glu Arg 
    130                 135                 140                 


Val Val Leu Val Ser Met Asn Tyr Arg Val Gly Ala Phe Gly Phe Leu 
145                 150                 155                 160 


Ala Leu Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gly Leu Leu Asp 
                165                 170                 175     


Gln Arg Leu Ala Leu Gln Trp Val Gln Glu Asn Ile Ala Ala Phe Gly 
            180                 185                 190         


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


Ser Val Gly Met His Leu Leu Ser Pro Pro Ser Arg Gly Leu Phe His 
    210                 215                 220                 


Arg Ala Ile Leu Gln Ser Gly Ala Pro Asn Ala Pro Trp Ala Thr Val 
225                 230                 235                 240 


Ser Met Glu Glu Ala Arg Arg Arg Ala Thr Gln Leu Ala Lys Leu Val 
                245                 250                 255     


Gly Cys Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Glu Leu Val Ala 
            260                 265                 270         


Cys Leu Arg Thr Arg Pro Pro Gln Glu Leu Val Asn His Glu Trp His 
        275                 280                 285             


Val Leu Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Val Pro Val Val 
    290                 295                 300                 


Asp Gly Asp Phe Leu Pro Asp Thr Pro Glu Ala Leu Ile Asn Asn Gly 
305                 310                 315                 320 


Asp Phe Lys Gly Leu Asp Val Leu Val Gly Val Asn Lys Asp Glu Gly 
                325                 330                 335     


Ser Tyr Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Glu 
            340                 345                 350         


Ser Leu Ile Ser Arg Glu Glu Phe Leu Ala Gly Val Arg Val Gly Val 
        355                 360                 365             


Pro Gln Val Ser Asp Leu Ala Ala Glu Ala Val Val Leu His Tyr Thr 
    370                 375                 380                 


Asp Trp Leu His Pro Glu Asp Pro Ala Arg Leu Arg Glu Ala Leu Ser 
385                 390                 395                 400 


Asp Val Val Gly Asp His Asn Val Ile Cys Pro Val Ala Gln Phe Ala 
                405                 410                 415     


Gln Arg Tyr Ala Ala Asn Gly Ala Arg Val Tyr Met Tyr Val Phe Glu 
            420                 425                 430         


His Arg Ser Ser Thr Leu Pro Trp Pro Glu Trp Met Gly Val Pro His 
        435                 440                 445             


Gly Tyr Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu Asp Pro Ser Arg 
    450                 455                 460                 


Asn Tyr Thr Glu Glu Glu Lys Ile Phe Ala Arg Arg Leu Met Arg Tyr 
465                 470                 475                 480 


Trp Ala Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pro Arg Asp Pro 
                485                 490                 495     


Lys Ala Pro Gln Trp Pro Pro Tyr Thr Ala Asp Ala Gln Lys Tyr Val 
            500                 505                 510         


Ser Leu Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Leu Arg Ala Gln 
        515                 520                 525             


Ala Cys Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Leu Ser Ala Thr 
    530                 535                 540                 


<210>  3
<211>  544
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding RhAChE_m0p45

<400>  3

Met Glu Gly Arg Glu Asp Ala Glu Leu Ile Val Thr Thr Arg Gly Gly 
1               5                   10                  15      


Lys Ile Arg Gly Ile Arg Leu Thr Thr Ile Gly Gly Pro Val Ser Ala 
            20                  25                  30          


Phe Leu Gly Ile Pro Phe Ala Glu Pro Pro Val Gly Pro Arg Arg Phe 
        35                  40                  45              


Arg Pro Pro Glu Pro Lys Arg Pro Trp Ser Gly Val Trp Asp Ala Thr 
    50                  55                  60                  


Thr Phe Gln Asn Val Cys Tyr Gln Tyr Val Asp Thr Leu Tyr Pro Gly 
65                  70                  75                  80  


Phe Pro Gly Thr Glu Met Trp Asn Pro Asn Arg Pro Leu Ser Glu Asp 
                85                  90                  95      


Cys Leu Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pro Lys Asn Pro 
            100                 105                 110         


Ala Pro Val Met Val Trp Ile Tyr Gly Gly Gly Phe Tyr Ser Gly Ser 
        115                 120                 125             


Ser Ser Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Arg Glu Glu Arg 
    130                 135                 140                 


Val Val Leu Val Ser Met Asn Tyr Arg Val Gly Ala Phe Gly Phe Leu 
145                 150                 155                 160 


Ala Leu Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gly Leu Leu Asp 
                165                 170                 175     


Gln Arg Leu Ala Leu Gln Trp Val Gln Glu Asn Ile Ala Ala Phe Gly 
            180                 185                 190         


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


Ser Val Gly Met His Leu Leu Ser Pro Pro Ser Arg Gly Leu Phe His 
    210                 215                 220                 


Arg Ala Ile Leu Gln Ser Gly Ala Pro Asn Ala Pro Trp Ala Tyr Val 
225                 230                 235                 240 


Ser Arg Glu Glu Ala Arg Arg Arg Ala Leu Gln Leu Ala Lys Leu Val 
                245                 250                 255     


Gly Cys Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Glu Leu Val Ala 
            260                 265                 270         


Cys Leu Arg Asn Arg Pro Ala Gln Glu Leu Val Asn His Glu Trp His 
        275                 280                 285             


Val Leu Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Val Pro Val Val 
    290                 295                 300                 


Asp Gly Ser Phe Leu Pro Asp Thr Pro Glu Ala Leu Ile Asn Asn Gly 
305                 310                 315                 320 


Asp Phe Lys Gly Leu Gln Val Leu Val Gly Val Asn Lys Asp Glu Gly 
                325                 330                 335     


Ser Tyr Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Glu 
            340                 345                 350         


Ser Leu Ile Ser Arg Glu Glu Phe Leu Glu Gly Val Arg Val Gly Val 
        355                 360                 365             


Pro Asn Val Ser Asp Leu Ala Ala Glu Ala Ile Val Leu His Tyr Thr 
    370                 375                 380                 


Asp Trp Leu His Pro Asp Asp Pro Glu Lys Asn Arg Asp Ala Leu Ala 
385                 390                 395                 400 


Asp Val Val Gly Asp His Asn Val Ile Cys Pro Val Ala Gln Phe Ala 
                405                 410                 415     


Glu Arg Tyr Ala Ala Asn Gly Ala Arg Val Tyr Ala Tyr Phe Phe Glu 
            420                 425                 430         


His Arg Ser Ser Thr Leu Pro Trp Pro Glu Trp Met Gly Val Pro His 
        435                 440                 445             


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


Asn Tyr Thr Lys Glu Glu Lys Ile Phe Ala Arg Arg Met Met Arg Tyr 
465                 470                 475                 480 


Trp Ala Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pro Arg Asp Pro 
                485                 490                 495     


Lys Ala Pro Gln Trp Pro Pro Tyr Thr Ala Asp Glu Gln Lys Tyr Val 
            500                 505                 510         


Ser Leu Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Leu Arg Ala Gln 
        515                 520                 525             


His Cys Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Leu Ser Met Thr 
    530                 535                 540                 


<210>  4
<211>  544
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding RhAChE_m0p7

<400>  4

Met Glu Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Thr Arg Gly Gly 
1               5                   10                  15      


Arg Leu Arg Gly Ile Arg Leu Thr Thr Pro Gly Gly Pro Val Ser Ala 
            20                  25                  30          


Phe Leu Gly Ile Pro Phe Ala Glu Pro Pro Val Gly Pro Arg Arg Phe 
        35                  40                  45              


Arg Pro Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Trp Asp Ala Thr 
    50                  55                  60                  


Thr Phe Gln Asn Val Cys Tyr Gln Tyr Val Asp Thr Leu Tyr Pro Gly 
65                  70                  75                  80  


Phe Glu Gly Thr Glu Met Trp Asn Pro Asn Arg Asn Leu Ser Glu Asp 
                85                  90                  95      


Cys Leu Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pro Lys Asn Pro 
            100                 105                 110         


Ala Pro Val Met Val Trp Ile Tyr Gly Gly Gly Phe Tyr Ser Gly Ser 
        115                 120                 125             


Ser Ser Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Arg Thr Glu Arg 
    130                 135                 140                 


Val Val Leu Val Ser Met Asn Tyr Arg Val Gly Ala Phe Gly Phe Leu 
145                 150                 155                 160 


Ala Leu Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gly Leu Leu Asp 
                165                 170                 175     


Gln Arg Leu Ala Leu Gln Trp Val Gln Glu Asn Ile Ala Ala Phe Gly 
            180                 185                 190         


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


Ser Val Gly Met His Leu Leu Ser Pro Pro Ser Arg Gly Leu Phe His 
    210                 215                 220                 


Arg Ala Ile Leu Gln Ser Gly Ala Pro Asn Ala Pro Trp Ala Tyr Val 
225                 230                 235                 240 


Ser Arg Glu Glu Ala Arg Arg Arg Ala Leu Gln Leu Ala Lys Leu Val 
                245                 250                 255     


Gly Cys Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Glu Leu Val Ala 
            260                 265                 270         


Cys Leu Arg Asn Arg Pro Pro Gln Glu Leu Val Asn His Glu Trp His 
        275                 280                 285             


Val Leu Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Val Pro Val Val 
    290                 295                 300                 


Asp Gly Asp Phe Leu Pro Asp Thr Pro Glu Ala Leu Ile Asn Asn Gly 
305                 310                 315                 320 


Asp Phe Lys Gly Leu Asp Val Leu Val Gly Val Asn Lys Asp Glu Gly 
                325                 330                 335     


Ser Tyr Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Glu 
            340                 345                 350         


Ser Leu Ile Ser Arg Glu Glu Phe Leu Glu Gly Val Arg Val Gly Val 
        355                 360                 365             


Pro Gln Val Ser Asp Leu Ala Ala Glu Ala Ile Val Leu His Tyr Thr 
    370                 375                 380                 


Asp Trp Leu His Pro Glu Asp Pro Ala Lys Asn Arg Asp Ala Leu Ser 
385                 390                 395                 400 


Asp Val Val Gly Asp His Asn Val Ile Cys Pro Val Ala Gln Phe Ala 
                405                 410                 415     


Gln Arg Tyr Ala Ala Asn Gly Ala Arg Val Tyr Ala Tyr Val Phe Glu 
            420                 425                 430         


His Arg Ser Ser Thr Leu Pro Trp Pro Glu Trp Met Gly Val Pro His 
        435                 440                 445             


Gly Tyr Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu Asp Pro Ser Arg 
    450                 455                 460                 


Asn Tyr Thr Lys Glu Glu Lys Ile Phe Ala Arg Arg Leu Met Arg Tyr 
465                 470                 475                 480 


Trp Ala Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pro Arg Asp Pro 
                485                 490                 495     


Lys Ala Pro Gln Trp Pro Pro Tyr Thr Ala Asp Glu Gln Lys Tyr Val 
            500                 505                 510         


Ser Leu Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Leu Arg Ala Gln 
        515                 520                 525             


Ala Cys Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Leu Ser Ala Thr 
    530                 535                 540                 


<210>  5
<211>  544
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding RhAChE_m1p2

<400>  5

Met Glu Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Thr Arg Gly Gly 
1               5                   10                  15      


Arg Leu Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pro Val Ser Ala 
            20                  25                  30          


Phe Leu Gly Ile Pro Phe Ala Glu Pro Pro Val Gly Pro Arg Arg Phe 
        35                  40                  45              


Arg Pro Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Trp Asp Ala Thr 
    50                  55                  60                  


Thr Phe Gln Asn Val Cys Tyr Gln Tyr Val Asp Thr Leu Tyr Pro Gly 
65                  70                  75                  80  


Phe Glu Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Leu Ser Glu Asp 
                85                  90                  95      


Cys Leu Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pro Thr Ser Pro 
            100                 105                 110         


Val Pro Val Met Val Trp Ile Tyr Gly Gly Gly Phe Tyr Ser Gly Ser 
        115                 120                 125             


Ser Ser Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Arg Ala Glu Arg 
    130                 135                 140                 


Val Val Leu Val Ser Met Asn Tyr Arg Val Gly Ala Phe Gly Phe Leu 
145                 150                 155                 160 


Ala Leu Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gly Leu Leu Asp 
                165                 170                 175     


Gln Arg Leu Ala Leu Gln Trp Val Gln Glu Asn Ile Ala Ala Phe Gly 
            180                 185                 190         


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


Ser Val Gly Met His Leu Leu Ser Pro Pro Ser Arg Gly Leu Phe His 
    210                 215                 220                 


Arg Ala Ile Leu Gln Ser Gly Ala Pro Asn Ala Pro Trp Ala Thr Val 
225                 230                 235                 240 


Ser Met Glu Glu Ala Arg Arg Arg Ala Thr Gln Leu Ala Lys Leu Val 
                245                 250                 255     


Gly Cys Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Glu Leu Val Ala 
            260                 265                 270         


Cys Leu Arg Thr Arg Pro Pro Gln Val Leu Val Asn His Glu Trp His 
        275                 280                 285             


Val Leu Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Val Pro Val Val 
    290                 295                 300                 


Asp Gly Asp Phe Leu Pro Asp Thr Pro Glu Ala Leu Ile Asn Asn Gly 
305                 310                 315                 320 


Asp Phe Lys Gly Leu Gln Val Leu Val Gly Val Asn Lys Asp Glu Gly 
                325                 330                 335     


Ser Tyr Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Glu 
            340                 345                 350         


Ser Leu Ile Ser Arg Glu Glu Phe Leu Ala Gly Val Arg Val Gly Val 
        355                 360                 365             


Pro Gln Val Ser Asp Leu Ala Ala Glu Ala Val Val Leu His Tyr Thr 
    370                 375                 380                 


Asp Trp Leu His Pro Glu Asp Pro Ala Arg Leu Arg Glu Ala Leu Ser 
385                 390                 395                 400 


Asp Val Val Gly Asp His Asn Val Val Cys Pro Val Ala Gln Phe Ala 
                405                 410                 415     


Gln Arg Tyr Ala Ala Gln Gly Ala Arg Val Tyr Met Tyr Val Phe Glu 
            420                 425                 430         


His Arg Ala Ser Thr Leu Pro Trp Pro Glu Trp Met Gly Val Pro His 
        435                 440                 445             


Gly Tyr Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu Asp Pro Ser Arg 
    450                 455                 460                 


Asn Tyr Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Leu Met Arg Tyr 
465                 470                 475                 480 


Trp Ala Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pro Arg Asp Pro 
                485                 490                 495     


Lys Ala Pro Gln Trp Pro Pro Tyr Thr Ala Asp Ala Gln Gln Tyr Val 
            500                 505                 510         


Ser Leu Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Leu Arg Ala Gln 
        515                 520                 525             


His Cys Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Leu Ser Ala Thr 
    530                 535                 540                 


<210>  6
<211>  544
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding RhAChE_m2p0

<400>  6

Met Glu Gly Arg Glu Asp Ala Glu Leu Leu Val Thr Val Arg Gly Gly 
1               5                   10                  15      


Arg Leu Arg Gly Ile Arg Leu Lys Thr Pro Gly Gly Pro Val Ser Ala 
            20                  25                  30          


Phe Leu Gly Ile Pro Phe Ala Glu Pro Pro Met Gly Pro Arg Arg Phe 
        35                  40                  45              


Arg Pro Pro Glu Pro Lys Gln Pro Trp Ser Gly Val Trp Asp Ala Thr 
    50                  55                  60                  


Thr Phe Gln Asn Val Cys Tyr Gln Tyr Val Asp Thr Leu Tyr Pro Gly 
65                  70                  75                  80  


Phe Glu Gly Thr Glu Met Trp Asn Pro Asn Arg Glu Leu Ser Glu Asp 
                85                  90                  95      


Cys Leu Tyr Leu Asn Val Trp Thr Pro Tyr Pro Arg Pro Thr Ser Pro 
            100                 105                 110         


Thr Pro Val Met Val Trp Ile Tyr Gly Gly Gly Phe Tyr Ser Gly Ser 
        115                 120                 125             


Ser Ser Leu Asp Val Tyr Asp Gly Arg Phe Leu Val Gln Ala Glu Arg 
    130                 135                 140                 


Val Val Leu Val Ser Met Asn Tyr Arg Val Gly Ala Phe Gly Phe Leu 
145                 150                 155                 160 


Ala Leu Pro Gly Ser Arg Glu Ala Pro Gly Asn Val Gly Leu Leu Asp 
                165                 170                 175     


Gln Arg Leu Ala Leu Gln Trp Val Gln Glu Asn Ile Ala Ala Phe Gly 
            180                 185                 190         


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


Ser Val Gly Met His Leu Leu Ser Pro Pro Ser Arg Gly Leu Phe His 
    210                 215                 220                 


Arg Ala Ile Leu Gln Ser Gly Ala Pro Asn Ala Pro Trp Ala Thr Val 
225                 230                 235                 240 


Ser Met Gly Glu Ala Arg Arg Arg Ala Thr Gln Leu Ala Lys Leu Val 
                245                 250                 255     


Gly Cys Pro Pro Gly Gly Thr Gly Gly Asn Asp Thr Glu Leu Val Ala 
            260                 265                 270         


Cys Leu Arg Thr Arg Pro Ala Gln Val Leu Val Asn His Glu Trp His 
        275                 280                 285             


Val Leu Pro Gln Glu Ser Val Phe Arg Phe Ser Phe Val Pro Val Val 
    290                 295                 300                 


Asp Gly Asp Phe Leu Ser Asp Thr Pro Glu Ala Leu Ile Asn Ala Gly 
305                 310                 315                 320 


Asp Phe His Gly Leu Gln Val Leu Val Gly Val Asn Lys Asp Glu Gly 
                325                 330                 335     


Ser Tyr Phe Leu Val Tyr Gly Ala Pro Gly Phe Ser Lys Asp Asn Glu 
            340                 345                 350         


Ser Leu Ile Ser Arg Ala Glu Phe Leu Ala Gly Val Arg Val Gly Val 
        355                 360                 365             


Pro Gln Val Ser Asp Leu Ala Ala Glu Ala Val Val Leu His Tyr Thr 
    370                 375                 380                 


Asp Trp Leu His Pro Glu Asp Pro Ala Arg Leu Arg Glu Ala Leu Ser 
385                 390                 395                 400 


Asp Val Val Gly Asp His Asn Val Val Cys Pro Val Ala Gln Phe Ala 
                405                 410                 415     


Gln Arg Tyr Ala Ala Gln Gly Ala Arg Val Tyr Ala Tyr Val Phe Glu 
            420                 425                 430         


His Arg Ala Ser Thr Leu Pro Trp Pro Glu Trp Met Gly Val Pro His 
        435                 440                 445             


Gly Tyr Glu Ile Glu Phe Ile Phe Gly Ile Pro Leu Asp Pro Ser Arg 
    450                 455                 460                 


Asn Tyr Thr Ala Glu Glu Lys Ile Phe Ala Gln Arg Leu Met Arg Tyr 
465                 470                 475                 480 


Trp Ala Asn Phe Ala Arg Thr Gly Asp Pro Asn Glu Pro Arg Asp Pro 
                485                 490                 495     


Lys Ala Pro Gln Trp Pro Pro Tyr Thr Ala Gly Ala Gln Gln Tyr Val 
            500                 505                 510         


Ser Leu Asp Leu Arg Pro Leu Glu Val Arg Arg Gly Leu Arg Ala Gln 
        515                 520                 525             


Ala Cys Ala Phe Trp Asn Arg Phe Leu Pro Lys Leu Leu Ser Ala Thr 
    530                 535                 540                 


<210>  7
<211>  342
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding PTE-S5  variant of PTE

<400>  7

Gly Arg Ile Ser Glu Phe Ile Thr Asn Ser Gly Asp Arg Ile Asn Thr 
1               5                   10                  15      


Val Arg Gly Pro Ile Thr Ile Ser Glu Ala Gly Phe Thr Leu Thr His 
            20                  25                  30          


Glu His Ile Cys Gly Ser Ser Ala Gly Phe Leu Arg Ala Trp Pro Glu 
        35                  40                  45              


Phe Phe Gly Ser Arg Lys Ala Leu Ala Glu Lys Ala Val Arg Gly Leu 
    50                  55                  60                  


Arg Arg Ala Arg Ala Ala Gly Val Arg Thr Ile Val Asp Val Ser Thr 
65                  70                  75                  80  


Phe Asp Ile Gly Arg Asp Val Ser Leu Leu Ala Glu Val Ser Arg Ala 
                85                  90                  95      


Ala Asp Val His Ile Val Ala Ala Thr Gly Leu Trp Phe Asp Pro Pro 
            100                 105                 110         


Leu Ser Met Arg Leu Arg Ser Val Glu Glu Leu Thr Gln Phe Phe Leu 
        115                 120                 125             


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


Ile Lys Val Ala Thr Thr Gly Lys Ala Thr Pro Phe Gln Glu Leu Val 
145                 150                 155                 160 


Leu Arg Ala Ala Ala Arg Ala Ser Leu Ala Thr Gly Val Pro Val Thr 
                165                 170                 175     


Thr His Thr Ala Ala Ser Gln Arg Gly Gly Glu Gln Gln Ala Ala Ile 
            180                 185                 190         


Phe Glu Ser Glu Gly Leu Ser Pro Ser Arg Val Cys Ile Gly His Ser 
        195                 200                 205             


Asp Asp Thr Asp Asp Leu Ser Tyr Leu Thr Ala Leu Ala Ala Arg Gly 
    210                 215                 220                 


Tyr Leu Ile Gly Leu Asp His Ile Pro His Ser Ala Ile Gly Leu Glu 
225                 230                 235                 240 


Asp Asn Ala Ser Ala Ser Ala Leu Leu Gly Ile Arg Ser Trp Gln Thr 
                245                 250                 255     


Arg Ala Leu Leu Ile Lys Ala Leu Ile Asp Gln Gly Tyr Met Lys Gln 
            260                 265                 270         


Ile Leu Val Ser Asn Asp Trp Leu Phe Gly Phe Ser Ser Tyr Val Thr 
        275                 280                 285             


Asn Ile Met Asp Val Met Asp Ser Val Asn Pro Asp Gly Met Ala Phe 
    290                 295                 300                 


Ile Pro Leu Arg Val Ile Pro Phe Leu Arg Glu Lys Gly Val Pro Gln 
305                 310                 315                 320 


Glu Thr Leu Ala Gly Ile Thr Val Thr Asn Pro Ala Arg Phe Leu Ser 
                325                 330                 335     


Pro Thr Leu Arg Ala Ser 
            340         


<210>  8
<211>  342
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding dPTE_m0p45

<400>  8

Gly Arg Ile Ser Glu Phe Ile Thr Asn Ser Gly Asp Arg Ile Asn Thr 
1               5                   10                  15      


Val Arg Gly Pro Ile Thr Ile Ser Glu Leu Gly Phe Thr Leu Met His 
            20                  25                  30          


Glu His Ile Cys Gly Ser Ser Ala Gly Phe Leu Arg Ala Trp Pro Glu 
        35                  40                  45              


Phe Phe Gly Ser Arg Asp Ala Leu Ala Glu Lys Ala Val Arg Gly Leu 
    50                  55                  60                  


Arg Arg Ala Arg Ala Ala Gly Val Asp Thr Ile Val Asp Val Ser Thr 
65                  70                  75                  80  


Phe Asp Ile Gly Arg Asp Val Glu Leu Leu Ala Glu Val Ala Glu Ala 
                85                  90                  95      


Ala Asp Val His Ile Val Ala Ala Thr Gly Leu Trp Phe Asp Pro Pro 
            100                 105                 110         


Leu Ser Met Arg Leu Arg Ser Val Glu Glu Leu Thr Gln Phe Phe Leu 
        115                 120                 125             


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


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


Leu Arg Ala Ala Ala Arg Ala Ser Leu Glu Thr Gly Val Pro Val Thr 
                165                 170                 175     


Thr His Thr Asp Ala Ser Gln Arg Asp Gly Glu Glu Gln Ala Asp Ile 
            180                 185                 190         


Phe Glu Ser Glu Gly Leu Asp Pro Ser Arg Val Cys Ile Gly His Ala 
        195                 200                 205             


Asp Asp Thr Asp Asp Leu Asp Tyr Leu Thr Glu Leu Ala Ala Arg Gly 
    210                 215                 220                 


Tyr Leu Ile Gly Leu Asp His Ile Pro His Ser Ala Ile Gly Leu Glu 
225                 230                 235                 240 


Asp Asn Ala Ser Ala Ala Ala Leu Leu Gly Leu Arg Ser Trp Gln Thr 
                245                 250                 255     


Arg Ala Leu Leu Ile Lys Ala Leu Ile Asp Gln Gly Tyr Ala Asp Gln 
            260                 265                 270         


Ile Leu Val Ser Asn Asp Trp Leu Phe Gly Phe Ser Ser Tyr Val Thr 
        275                 280                 285             


Asn Ile Met Asp Val Met Asp Arg Val Asn Pro Asp Gly Met Ala His 
    290                 295                 300                 


Ile Pro Glu Arg Val Ile Pro Phe Leu Arg Glu Lys Gly Val Pro Asp 
305                 310                 315                 320 


Glu Thr Leu Asp Thr Ile Met Val Glu Asn Pro Ala Arg Phe Leu Ser 
                325                 330                 335     


Pro Thr Leu Arg Ala Ser 
            340         


<210>  9
<211>  342
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding dPTE_m1p00

<400>  9

Gly Arg Ile Ser Glu Phe Ile Thr Asn Ser Gly Asp Arg Ile Asn Thr 
1               5                   10                  15      


Val Arg Gly Pro Ile Thr Ile Ser Glu Ala Gly Phe Thr Leu Met His 
            20                  25                  30          


Glu His Ile Cys Gly Ser Ser Ala Gly Phe Leu Arg Ala Trp Pro Glu 
        35                  40                  45              


Phe Phe Gly Ser Arg Asp Ala Leu Ala Glu Lys Ala Val Arg Gly Leu 
    50                  55                  60                  


Arg Arg Ala Arg Ala Ala Gly Val Arg Thr Ile Val Asp Val Ser Thr 
65                  70                  75                  80  


Phe Asp Ile Gly Arg Asp Val Glu Leu Leu Ala Glu Val Ser Glu Ala 
                85                  90                  95      


Ala Asp Val His Ile Val Ala Ala Thr Gly Leu Trp Phe Asp Pro Pro 
            100                 105                 110         


Leu Ser Met Arg Leu Arg Ser Val Glu Glu Leu Thr Gln Phe Phe Leu 
        115                 120                 125             


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


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


Leu Arg Ala Ala Ala Arg Ala Ser Leu Ala Thr Gly Val Pro Val Thr 
                165                 170                 175     


Thr His Thr Asp Ala Ser Gln Arg Asp Gly Glu Gln Gln Ala Asp Ile 
            180                 185                 190         


Phe Glu Ser Glu Gly Leu Asp Pro Ser Arg Val Cys Ile Gly His Ser 
        195                 200                 205             


Asp Asp Thr Asp Asp Leu Asp Tyr Leu Thr Ala Leu Ala Ala Arg Gly 
    210                 215                 220                 


Tyr Leu Ile Gly Leu Asp His Ile Pro His Ser Ala Ile Gly Leu Glu 
225                 230                 235                 240 


Asp Asn Ala Ser Ala Ala Ala Leu Leu Gly Leu Arg Ser Trp Gln Thr 
                245                 250                 255     


Arg Ala Leu Leu Ile Lys Ala Leu Ile Asp Gln Gly Tyr Ala Asp Gln 
            260                 265                 270         


Ile Leu Val Ser Asn Asp Trp Leu Phe Gly Phe Ser Ser Tyr Val Thr 
        275                 280                 285             


Asn Ile Met Asp Val Met Asp Arg Val Asn Pro Asp Gly Met Ala Phe 
    290                 295                 300                 


Ile Pro Leu Arg Val Ile Pro Phe Leu Arg Glu Lys Gly Val Pro Asp 
305                 310                 315                 320 


Glu Thr Leu Glu Thr Ile Met Val Asp Asn Pro Ala Arg Phe Leu Ser 
                325                 330                 335     


Pro Thr Leu Arg Ala Ser 
            340         


<210>  10
<211>  342
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding dPTE_m2p00

<400>  10

Gly Arg Ile Ser Glu Phe Ile Thr Asn Ser Gly Asp Arg Ile Asn Thr 
1               5                   10                  15      


Val Arg Gly Pro Ile Thr Ile Ser Glu Ala Gly Phe Thr Leu Thr His 
            20                  25                  30          


Glu His Ile Cys Gly Ser Ser Ala Gly Phe Leu Arg Ala Trp Pro Glu 
        35                  40                  45              


Phe Phe Gly Ser Arg Asp Ala Leu Ala Glu Lys Ala Val Arg Gly Leu 
    50                  55                  60                  


Arg Arg Ala Arg Ala Ala Gly Val Arg Thr Ile Val Asp Val Ser Thr 
65                  70                  75                  80  


Phe Asp Ile Gly Arg Asp Val Ser Leu Leu Ala Glu Val Ser Glu Ala 
                85                  90                  95      


Ala Asp Val His Ile Val Ala Ala Thr Gly Leu Trp Phe Asp Pro Pro 
            100                 105                 110         


Leu Ser Met Arg Leu Arg Ser Val Glu Glu Leu Thr Gln Phe Phe Leu 
        115                 120                 125             


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


Ile Lys Val Ala Thr Thr Gly Lys Ala Thr Pro Phe Gln Glu Leu Val 
145                 150                 155                 160 


Leu Arg Ala Ala Ala Arg Ala Ser Leu Ala Thr Gly Val Pro Val Thr 
                165                 170                 175     


Thr His Thr Asp Ala Ser Gln Arg Asp Gly Glu Gln Gln Ala Ala Ile 
            180                 185                 190         


Phe Glu Ser Glu Gly Leu Asp Pro Ser Arg Val Cys Ile Gly His Ser 
        195                 200                 205             


Asp Asp Thr Asp Asp Leu Asp Tyr Leu Thr Ala Leu Ala Ala Arg Gly 
    210                 215                 220                 


Tyr Leu Ile Gly Leu Asp His Ile Pro His Ser Ala Ile Gly Leu Glu 
225                 230                 235                 240 


Asp Asn Ala Ser Ala Ser Ala Leu Leu Gly Ile Arg Ser Trp Gln Thr 
                245                 250                 255     


Arg Ala Leu Leu Ile Lys Ala Leu Ile Asp Gln Gly Tyr Val Lys Gln 
            260                 265                 270         


Ile Leu Val Ser Asn Asp Trp Leu Phe Gly Phe Ser Ser Tyr Val Thr 
        275                 280                 285             


Asn Ile Met Asp Val Met Asp Arg Val Asn Pro Asp Gly Met Ala Phe 
    290                 295                 300                 


Ile Pro Leu Arg Val Ile Pro Phe Leu Arg Glu Lys Gly Val Pro Gln 
305                 310                 315                 320 


Glu Thr Leu Ala Thr Ile Thr Val Glu Asn Pro Ala Arg Phe Leu Ser 
                325                 330                 335     


Pro Thr Leu Arg Ala Ser 
            340         


<210>  11
<211>  287
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Amino Acid sequence encoding Dnmt3a_Stab

<400>  11

Met Pro Ala Glu Lys Arg Lys Pro Ile Arg Val Leu Ser Leu Phe Asp 
1               5                   10                  15      


Gly Ile Ala Thr Gly Leu Leu Val Leu Lys Asp Leu Gly Ile Gln Val 
            20                  25                  30          


Asp Arg Tyr Ile Ala Ser Glu Val Cys Glu Asp Ser Ile Thr Val Gly 
        35                  40                  45              


Met Val Arg His Gln Gly Asn Ile Met Tyr Val Gly Asp Val Arg Asn 
    50                  55                  60                  


Ile Thr Gln Lys His Ile Asp Glu Trp Gly Pro Phe Asp Leu Val Ile 
65                  70                  75                  80  


Gly Gly Ser Pro Cys Asn Asp Leu Ser Ile Val Asn Pro Ala Arg Lys 
                85                  90                  95      


Gly Leu Tyr Glu Gly Thr Gly Arg Leu Phe Phe Glu Phe Tyr Arg Leu 
            100                 105                 110         


Leu His Asp Ala Arg Pro Lys Glu Gly Asp Asp Arg Pro Phe Phe Trp 
        115                 120                 125             


Leu Phe Glu Asn Val Val Ala Met Arg Val Asn Asp Lys Arg Asp Ile 
    130                 135                 140                 


Ser Arg Phe Leu Glu Cys Asn Pro Val Met Ile Asp Ala Lys Glu Val 
145                 150                 155                 160 


Ser Ala Ala His Arg Ala Arg Tyr Phe Trp Gly Asn Leu Pro Gly Met 
                165                 170                 175     


Asn Arg Pro Leu Cys Pro Ser Lys Asn Asp Lys Leu Glu Leu Gln Glu 
            180                 185                 190         


Cys Leu Glu His Gly Arg Gln Ala Lys Phe Ser Lys Val Arg Thr Ile 
        195                 200                 205             


Thr Thr Arg Ser Asn Ser Ile Lys Gln Gly Lys Asp Gln His Phe Pro 
    210                 215                 220                 


Val Phe Met Asn Gly Lys Glu Asp Ile Leu Trp Cys Thr Glu Met Glu 
225                 230                 235                 240 


Arg Val Phe Gly Phe Pro Asp His Tyr Thr Asp Val Ser Asn Met Ser 
                245                 250                 255     


Arg Leu Ala Arg Gln Arg Leu Leu Gly Arg Ser Trp Ser Val Pro Val 
            260                 265                 270         


Ile Arg His Leu Phe Ala Pro Leu Lys Asp Tyr Phe Ala Cys Val 
        275                 280                 285         


