                         SEQUENCE LISTING

<110>  Valerion Therapeutics, LLC
 
<120>  METHODS AND COMPOSITIONS FOR TREATMENT OF POLYGLUCOSAN DISORDERS

<130>  VLRN-039-WO1

<140>  PCT/US2019/022566
<141>  2019-03-15

<150>  US 62/643,592
<151>  2018-03-15

<160>  53    

<170>  PatentIn version 3.5

<210>  1
<211>  496
<212>  PRT
<213>  Homo sapiens

<400>  1

Gln Tyr Ser Pro Asn Thr Gln Gln Gly Arg Thr Ser Ile Val His Leu 
1               5                   10                  15      


Phe Glu Trp Arg Trp Val Asp Ile Ala Leu Glu Cys Glu Arg Tyr Leu 
            20                  25                  30          


Ala Pro Lys Gly Phe Gly Gly Val Gln Val Ser Pro Pro Asn Glu Asn 
        35                  40                  45              


Val Ala Ile Tyr Asn Pro Phe Arg Pro Trp Trp Glu Arg Tyr Gln Pro 
    50                  55                  60                  


Val Ser Tyr Lys Leu Cys Thr Arg Ser Gly Asn Glu Asp Glu Phe Arg 
65                  70                  75                  80  


Asn Met Val Thr Arg Cys Asn Asn Val Gly Val Arg Ile Tyr Val Asp 
                85                  90                  95      


Ala Val Ile Asn His Met Cys Gly Asn Ala Val Ser Ala Gly Thr Ser 
            100                 105                 110         


Ser Thr Cys Gly Ser Tyr Phe Asn Pro Gly Ser Arg Asp Phe Pro Ala 
        115                 120                 125             


Val Pro Tyr Ser Gly Trp Asp Phe Asn Asp Gly Lys Cys Lys Thr Gly 
    130                 135                 140                 


Ser Gly Asp Ile Glu Asn Tyr Asn Asp Ala Thr Gln Val Arg Asp Cys 
145                 150                 155                 160 


Arg Leu Thr Gly Leu Leu Asp Leu Ala Leu Glu Lys Asp Tyr Val Arg 
                165                 170                 175     


Ser Lys Ile Ala Glu Tyr Met Asn His Leu Ile Asp Ile Gly Val Ala 
            180                 185                 190         


Gly Phe Arg Leu Asp Ala Ser Lys His Met Trp Pro Gly Asp Ile Lys 
        195                 200                 205             


Ala Ile Leu Asp Lys Leu His Asn Leu Asn Ser Asn Trp Phe Pro Ala 
    210                 215                 220                 


Gly Ser Lys Pro Phe Ile Tyr Gln Glu Val Ile Asp Leu Gly Gly Glu 
225                 230                 235                 240 


Pro Ile Lys Ser Ser Asp Tyr Phe Gly Asn Gly Arg Val Thr Glu Phe 
                245                 250                 255     


Lys Tyr Gly Ala Lys Leu Gly Thr Val Ile Arg Lys Trp Asn Gly Glu 
            260                 265                 270         


Lys Met Ser Tyr Leu Lys Asn Trp Gly Glu Gly Trp Gly Phe Val Pro 
        275                 280                 285             


Ser Asp Arg Ala Leu Val Phe Val Asp Asn His Asp Asn Gln Arg Gly 
    290                 295                 300                 


His Gly Ala Gly Gly Ala Ser Ile Leu Thr Phe Trp Asp Ala Arg Leu 
305                 310                 315                 320 


Tyr Lys Met Ala Val Gly Phe Met Leu Ala His Pro Tyr Gly Phe Thr 
                325                 330                 335     


Arg Val Met Ser Ser Tyr Arg Trp Pro Arg Gln Phe Gln Asn Gly Asn 
            340                 345                 350         


Asp Val Asn Asp Trp Val Gly Pro Pro Asn Asn Asn Gly Val Ile Lys 
        355                 360                 365             


Glu Val Thr Ile Asn Pro Asp Thr Thr Cys Gly Asn Asp Trp Val Cys 
    370                 375                 380                 


Glu His Arg Trp Arg Gln Ile Arg Asn Met Val Ile Phe Arg Asn Val 
385                 390                 395                 400 


Val Asp Gly Gln Pro Phe Thr Asn Trp Tyr Asp Asn Gly Ser Asn Gln 
                405                 410                 415     


Val Ala Phe Gly Arg Gly Asn Arg Gly Phe Ile Val Phe Asn Asn Asp 
            420                 425                 430         


Asp Trp Ser Phe Ser Leu Thr Leu Gln Thr Gly Leu Pro Ala Gly Thr 
        435                 440                 445             


Tyr Cys Asp Val Ile Ser Gly Asp Lys Ile Asn Gly Asn Cys Thr Gly 
    450                 455                 460                 


Ile Lys Ile Tyr Val Ser Asp Asp Gly Lys Ala His Phe Ser Ile Ser 
465                 470                 475                 480 


Asn Ser Ala Glu Asp Pro Phe Ile Ala Ile His Ala Glu Ser Lys Leu 
                485                 490                 495     


<210>  2
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  2

Glu Val Gln Leu Gln Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  3
<211>  111
<212>  PRT
<213>  Homo sapiens

<400>  3

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


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser Thr Ser 
            20                  25                  30          


Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Tyr Ala Ser Tyr Leu Gln Ser Gly Val Pro Ser 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Glu Phe Pro Trp Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105                 110     


<210>  4
<211>  19
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy Chain Leader Sequence

<400>  4

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys 
            


<210>  5
<211>  22
<212>  PRT
<213>  Artificial

<220>
<223>  Light Chain Leader Amino Acid Sequence

<400>  5

Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Arg Gly Ala Arg Cys 
            20          


<210>  6
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  Glycine-Serine Linker

<400>  6

Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 
1               5                   10              


<210>  7
<211>  224
<212>  PRT
<213>  Homo sapiens

<400>  7

Glu Val Gln Leu Gln Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
        115                 120                 125             


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
    210                 215                 220                 


<210>  8
<211>  218
<212>  PRT
<213>  Homo sapiens

<400>  8

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


Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser Thr Ser 
            20                  25                  30          


Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Tyr Ala Ser Tyr Leu Gln Ser Gly Val Pro Ser 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Glu Phe Pro Trp Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg 
            100                 105                 110         


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
        115                 120                 125             


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
            180                 185                 190         


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
        195                 200                 205             


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             


<210>  9
<211>  752
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy Chain + Alpha-Amylase Fusion Protein

<400>  9

Met Glu Phe Gly Leu Ser Trp Leu Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys Glu Val Gln Leu Gln Glu Ser Gly Gly Gly Val Val Gln 
            20                  25                  30          


Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe 
        35                  40                  45              


Ser Asn Tyr Gly Met His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Val Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala 
65                  70                  75                  80  


Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn 
                85                  90                  95      


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


Tyr Tyr Cys Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly 
        115                 120                 125             


Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
    130                 135                 140                 


Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
145                 150                 155                 160 


Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp 
                165                 170                 175     


Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
            180                 185                 190         


Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
        195                 200                 205             


Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro 
    210                 215                 220                 


Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys 
225                 230                 235                 240 


Thr His Thr Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly 
                245                 250                 255     


Gln Tyr Ser Pro Asn Thr Gln Gln Gly Arg Thr Ser Ile Val His Leu 
            260                 265                 270         


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


Ala Pro Lys Gly Phe Gly Gly Val Gln Val Ser Pro Pro Asn Glu Asn 
    290                 295                 300                 


Val Ala Ile Tyr Asn Pro Phe Arg Pro Trp Trp Glu Arg Tyr Gln Pro 
305                 310                 315                 320 


Val Ser Tyr Lys Leu Cys Thr Arg Ser Gly Asn Glu Asp Glu Phe Arg 
                325                 330                 335     


Asn Met Val Thr Arg Cys Asn Asn Val Gly Val Arg Ile Tyr Val Asp 
            340                 345                 350         


Ala Val Ile Asn His Met Cys Gly Asn Ala Val Ser Ala Gly Thr Ser 
        355                 360                 365             


Ser Thr Cys Gly Ser Tyr Phe Asn Pro Gly Ser Arg Asp Phe Pro Ala 
    370                 375                 380                 


Val Pro Tyr Ser Gly Trp Asp Phe Asn Asp Gly Lys Cys Lys Thr Gly 
385                 390                 395                 400 


Ser Gly Asp Ile Glu Asn Tyr Asn Asp Ala Thr Gln Val Arg Asp Cys 
                405                 410                 415     


Arg Leu Thr Gly Leu Leu Asp Leu Ala Leu Glu Lys Asp Tyr Val Arg 
            420                 425                 430         


Ser Lys Ile Ala Glu Tyr Met Asn His Leu Ile Asp Ile Gly Val Ala 
        435                 440                 445             


Gly Phe Arg Leu Asp Ala Ser Lys His Met Trp Pro Gly Asp Ile Lys 
    450                 455                 460                 


Ala Ile Leu Asp Lys Leu His Asn Leu Asn Ser Asn Trp Phe Pro Ala 
465                 470                 475                 480 


Gly Ser Lys Pro Phe Ile Tyr Gln Glu Val Ile Asp Leu Gly Gly Glu 
                485                 490                 495     


Pro Ile Lys Ser Ser Asp Tyr Phe Gly Asn Gly Arg Val Thr Glu Phe 
            500                 505                 510         


Lys Tyr Gly Ala Lys Leu Gly Thr Val Ile Arg Lys Trp Asn Gly Glu 
        515                 520                 525             


Lys Met Ser Tyr Leu Lys Asn Trp Gly Glu Gly Trp Gly Phe Val Pro 
    530                 535                 540                 


Ser Asp Arg Ala Leu Val Phe Val Asp Asn His Asp Asn Gln Arg Gly 
545                 550                 555                 560 


His Gly Ala Gly Gly Ala Ser Ile Leu Thr Phe Trp Asp Ala Arg Leu 
                565                 570                 575     


Tyr Lys Met Ala Val Gly Phe Met Leu Ala His Pro Tyr Gly Phe Thr 
            580                 585                 590         


Arg Val Met Ser Ser Tyr Arg Trp Pro Arg Gln Phe Gln Asn Gly Asn 
        595                 600                 605             


Asp Val Asn Asp Trp Val Gly Pro Pro Asn Asn Asn Gly Val Ile Lys 
    610                 615                 620                 


Glu Val Thr Ile Asn Pro Asp Thr Thr Cys Gly Asn Asp Trp Val Cys 
625                 630                 635                 640 


Glu His Arg Trp Arg Gln Ile Arg Asn Met Val Ile Phe Arg Asn Val 
                645                 650                 655     


Val Asp Gly Gln Pro Phe Thr Asn Trp Tyr Asp Asn Gly Ser Asn Gln 
            660                 665                 670         


Val Ala Phe Gly Arg Gly Asn Arg Gly Phe Ile Val Phe Asn Asn Asp 
        675                 680                 685             


Asp Trp Ser Phe Ser Leu Thr Leu Gln Thr Gly Leu Pro Ala Gly Thr 
    690                 695                 700                 


Tyr Cys Asp Val Ile Ser Gly Asp Lys Ile Asn Gly Asn Cys Thr Gly 
705                 710                 715                 720 


Ile Lys Ile Tyr Val Ser Asp Asp Gly Lys Ala His Phe Ser Ile Ser 
                725                 730                 735     


Asn Ser Ala Glu Asp Pro Phe Ile Ala Ile His Ala Glu Ser Lys Leu 
            740                 745                 750         


<210>  10
<211>  240
<212>  PRT
<213>  Artificial

<220>
<223>  Light Chain + Leader Sequence

<400>  10

Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


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


Lys Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln 
    50                  55                  60                  


Lys Pro Glu Lys Ala Pro Lys Leu Leu Ile Lys Tyr Ala Ser Tyr Leu 
65                  70                  75                  80  


Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                85                  90                  95      


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Val Ala Thr Tyr 
            100                 105                 110         


Tyr Cys Gln His Ser Arg Glu Phe Pro Trp Thr Phe Gly Ala Gly Thr 
        115                 120                 125             


Lys Leu Glu Leu Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe 
    130                 135                 140                 


Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys 
145                 150                 155                 160 


Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val 
                165                 170                 175     


Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln 
            180                 185                 190         


Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser 
        195                 200                 205             


Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His 
    210                 215                 220                 


Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 235                 240 


<210>  11
<211>  108
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy Chain IgG1 CH1 and Truncated Hinge Constant Domain

<400>  11

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      


Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
    50                  55                  60                  


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  


Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
            100                 105             


<210>  12
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  12

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
1               5                   10                  15      


Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
            20                  25                  30          


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
65                  70                  75                  80  


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                85                  90                  95      


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  13
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  GS3 linker

<400>  13

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  14
<211>  14
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  14

Gly Ser Thr Ser Gly Ser Gly Lys Ser Ser Glu Gly Lys Gly 
1               5                   10                  


<210>  15
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  His tag

<400>  15

His His His His His His His 
1               5           


<210>  16
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  c-Myc tag

<400>  16

Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
1               5                   10  


<210>  17
<211>  116
<212>  PRT
<213>  Artificial

<220>
<223>  3E10 Variable Heavy Chain

<400>  17

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 
1               5                   10                  15      


Ser Arg Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Val Arg Gln Ala Pro Glu Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Thr Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Phe 
65                  70                  75                  80  


Leu Gln Met Thr Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Thr Leu 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  18
<211>  111
<212>  PRT
<213>  Artificial

<220>
<223>  3E10 Variable Light Chain

<400>  18

Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly 
1               5                   10                  15      


Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Lys Ser Val Ser Thr Ser 
            20                  25                  30          


Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Tyr Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe His Leu Asn Ile His 
65                  70                  75                  80  


Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Glu Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys 
            100                 105                 110     


<210>  19
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR1 of 3E10 VH

<400>  19

Asn Tyr Gly Met His 
1               5   


<210>  20
<211>  17
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR2 of 3E10 VH

<400>  20

Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Thr Val Lys 
1               5                   10                  15      


Gly 
    


<210>  21
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR3 of 3E10 VH

<400>  21

Arg Gly Leu Leu Leu Asp Tyr 
1               5           


<210>  22
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR1 of 3E10 VL

<400>  22

Arg Ala Ser Lys Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met His 
1               5                   10                  15  


<210>  23
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR2 of 3E10 VL

<400>  23

Tyr Ala Ser Tyr Leu Glu Ser 
1               5           


<210>  24
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR3 of 3E10 VL

<400>  24

Gln His Ser Arg Glu Phe Pro Trp Thr 
1               5                   


<210>  25
<211>  4
<212>  PRT
<213>  Artificial

<220>
<223>  "AGIH"

<400>  25

Ala Gly Ile His 
1               


<210>  26
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  "SAGIH"

<400>  26

Ser Ala Gly Ile His 
1               5   


<210>  27
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR1 of 3E10 molecule

<400>  27

Gly Phe Thr Phe Ser Asn Tyr Gly 
1               5               


<210>  28
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR2 of 3E10 molecule

<400>  28

Ile Ser Ser Gly Ser Ser Thr Ile 
1               5               


<210>  29
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR3 of 3E10 molecule

<400>  29

Ala Arg Arg Gly Leu Leu Leu Asp Tyr 
1               5                   


<210>  30
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR1 of 3E10 molecule

<400>  30

Lys Ser Val Ser Thr Ser Ser Tyr Ser Tyr 
1               5                   10  


<210>  31
<211>  3
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR2 of 3E10 molecule

<400>  31

Tyr Ala Ser 
1           


<210>  32
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR3 of 3E10 molecule

<400>  32

Gln His Ser Arg Glu Phe Pro Trp Thr 
1               5                   


<210>  33
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  33

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  34
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  34

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Thr Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Thr Leu 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  35
<211>  111
<212>  PRT
<213>  Homo sapiens

<400>  35

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Lys Ser Val Ser Thr Ser 
            20                  25                  30          


Ser Tyr Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro 
        35                  40                  45              


Lys Leu Leu Ile Lys Tyr Ala Ser Tyr Leu Gln Ser Gly Val Pro Ser 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Glu Phe Pro Trp Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105                 110     


<210>  36
<211>  511
<212>  PRT
<213>  Homo sapiens

<400>  36

Met Lys Phe Phe Leu Leu Leu Phe Thr Ile Gly Phe Cys Trp Ala Gln 
1               5                   10                  15      


Tyr Ser Pro Asn Thr Gln Gln Gly Arg Thr Ser Ile Val His Leu Phe 
            20                  25                  30          


Glu Trp Arg Trp Val Asp Ile Ala Leu Glu Cys Glu Arg Tyr Leu Ala 
        35                  40                  45              


Pro Lys Gly Phe Gly Gly Val Gln Val Ser Pro Pro Asn Glu Asn Val 
    50                  55                  60                  


Ala Ile Tyr Asn Pro Phe Arg Pro Trp Trp Glu Arg Tyr Gln Pro Val 
65                  70                  75                  80  


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


Met Val Thr Arg Cys Asn Asn Val Gly Val Arg Ile Tyr Val Asp Ala 
            100                 105                 110         


Val Ile Asn His Met Cys Gly Asn Ala Val Ser Ala Gly Thr Ser Ser 
        115                 120                 125             


Thr Cys Gly Ser Tyr Phe Asn Pro Gly Ser Arg Asp Phe Pro Ala Val 
    130                 135                 140                 


Pro Tyr Ser Gly Trp Asp Phe Asn Asp Gly Lys Cys Lys Thr Gly Ser 
145                 150                 155                 160 


Gly Asp Ile Glu Asn Tyr Asn Asp Ala Thr Gln Val Arg Asp Cys Arg 
                165                 170                 175     


Leu Thr Gly Leu Leu Asp Leu Ala Leu Glu Lys Asp Tyr Val Arg Ser 
            180                 185                 190         


Lys Ile Ala Glu Tyr Met Asn His Leu Ile Asp Ile Gly Val Ala Gly 
        195                 200                 205             


Phe Arg Leu Asp Ala Ser Lys His Met Trp Pro Gly Asp Ile Lys Ala 
    210                 215                 220                 


Ile Leu Asp Lys Leu His Asn Leu Asn Ser Asn Trp Phe Pro Ala Gly 
225                 230                 235                 240 


Ser Lys Pro Phe Ile Tyr Gln Glu Val Ile Asp Leu Gly Gly Glu Pro 
                245                 250                 255     


Ile Lys Ser Ser Asp Tyr Phe Gly Asn Gly Arg Val Thr Glu Phe Lys 
            260                 265                 270         


Tyr Gly Ala Lys Leu Gly Thr Val Ile Arg Lys Trp Asn Gly Glu Lys 
        275                 280                 285             


Met Ser Tyr Leu Lys Asn Trp Gly Glu Gly Trp Gly Phe Val Pro Ser 
    290                 295                 300                 


Asp Arg Ala Leu Val Phe Val Asp Asn His Asp Asn Gln Arg Gly His 
305                 310                 315                 320 


Gly Ala Gly Gly Ala Ser Ile Leu Thr Phe Trp Asp Ala Arg Leu Tyr 
                325                 330                 335     


Lys Met Ala Val Gly Phe Met Leu Ala His Pro Tyr Gly Phe Thr Arg 
            340                 345                 350         


Val Met Ser Ser Tyr Arg Trp Pro Arg Gln Phe Gln Asn Gly Asn Asp 
        355                 360                 365             


Val Asn Asp Trp Val Gly Pro Pro Asn Asn Asn Gly Val Ile Lys Glu 
    370                 375                 380                 


Val Thr Ile Asn Pro Asp Thr Thr Cys Gly Asn Asp Trp Val Cys Glu 
385                 390                 395                 400 


His Arg Trp Arg Gln Ile Arg Asn Met Val Ile Phe Arg Asn Val Val 
                405                 410                 415     


Asp Gly Gln Pro Phe Thr Asn Trp Tyr Asp Asn Gly Ser Asn Gln Val 
            420                 425                 430         


Ala Phe Gly Arg Gly Asn Arg Gly Phe Ile Val Phe Asn Asn Asp Asp 
        435                 440                 445             


Trp Ser Phe Ser Leu Thr Leu Gln Thr Gly Leu Pro Ala Gly Thr Tyr 
    450                 455                 460                 


Cys Asp Val Ile Ser Gly Asp Lys Ile Asn Gly Asn Cys Thr Gly Ile 
465                 470                 475                 480 


Lys Ile Tyr Val Ser Asp Asp Gly Lys Ala His Phe Ser Ile Ser Asn 
                485                 490                 495     


Ser Ala Glu Asp Pro Phe Ile Ala Ile His Ala Glu Ser Lys Leu 
            500                 505                 510     


<210>  37
<211>  17
<212>  PRT
<213>  Artificial

<220>
<223>  heavy chain variable domain CDR2

<400>  37

Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  38
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR1

<400>  38

Arg Ala Ser Lys Ser Val Ser Thr Ser Ser Tyr Ser Tyr Leu Ala 
1               5                   10                  15  


<210>  39
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  light chain variable domain CDR2

<400>  39

Tyr Ala Ser Tyr Leu Gln Ser 
1               5           


<210>  40
<211>  111
<212>  PRT
<213>  Homo sapiens

<400>  40

Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Pro Gly 
1               5                   10                  15      


Gln Arg Ala Thr Ile Thr Cys Arg Ala Ser Lys Ser Val Ser Thr Ser 
            20                  25                  30          


Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Tyr Tyr Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn 
65                  70                  75                  80  


Pro Val Glu Ala Asn Asp Thr Ala Asn Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Glu Phe Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110     


<210>  41
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  41

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ser Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Val 
        35                  40                  45              


Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Thr Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Val Lys Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  42
<211>  242
<212>  PRT
<213>  Homo sapiens

<400>  42

Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Pro Gly 
1               5                   10                  15      


Gln Arg Ala Thr Ile Thr Cys Arg Ala Ser Lys Ser Val Ser Thr Ser 
            20                  25                  30          


Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


Lys Leu Leu Ile Tyr Tyr Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn 
65                  70                  75                  80  


Pro Val Glu Ala Asn Asp Thr Ala Asn Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Glu Phe Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
        115                 120                 125             


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
    130                 135                 140                 


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


His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr Val Ser Tyr 
                165                 170                 175     


Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Thr Val Lys Gly 
            180                 185                 190         


Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 
        195                 200                 205             


Met Ser Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val Lys 
    210                 215                 220                 


Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
225                 230                 235                 240 


Ser Ser 
        


<210>  43
<211>  733
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy Chain + Alpha-Amylase Fusion Protein

<400>  43

Glu Val Gln Leu Gln Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn Tyr 
            20                  25                  30          


Gly Met His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Tyr Ile Ser Ser Gly Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Gly Leu Leu Leu Asp Tyr Trp Gly Gln Gly Thr Leu Val 
            100                 105                 110         


Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala 
        115                 120                 125             


Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu 
    130                 135                 140                 


Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly 
145                 150                 155                 160 


Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser 
                165                 170                 175     


Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu 
            180                 185                 190         


Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr 
        195                 200                 205             


Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
    210                 215                 220                 


Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gln Tyr Ser 
225                 230                 235                 240 


Pro Asn Thr Gln Gln Gly Arg Thr Ser Ile Val His Leu Phe Glu Trp 
                245                 250                 255     


Arg Trp Val Asp Ile Ala Leu Glu Cys Glu Arg Tyr Leu Ala Pro Lys 
            260                 265                 270         


Gly Phe Gly Gly Val Gln Val Ser Pro Pro Asn Glu Asn Val Ala Ile 
        275                 280                 285             


Tyr Asn Pro Phe Arg Pro Trp Trp Glu Arg Tyr Gln Pro Val Ser Tyr 
    290                 295                 300                 


Lys Leu Cys Thr Arg Ser Gly Asn Glu Asp Glu Phe Arg Asn Met Val 
305                 310                 315                 320 


Thr Arg Cys Asn Asn Val Gly Val Arg Ile Tyr Val Asp Ala Val Ile 
                325                 330                 335     


Asn His Met Cys Gly Asn Ala Val Ser Ala Gly Thr Ser Ser Thr Cys 
            340                 345                 350         


Gly Ser Tyr Phe Asn Pro Gly Ser Arg Asp Phe Pro Ala Val Pro Tyr 
        355                 360                 365             


Ser Gly Trp Asp Phe Asn Asp Gly Lys Cys Lys Thr Gly Ser Gly Asp 
    370                 375                 380                 


Ile Glu Asn Tyr Asn Asp Ala Thr Gln Val Arg Asp Cys Arg Leu Thr 
385                 390                 395                 400 


Gly Leu Leu Asp Leu Ala Leu Glu Lys Asp Tyr Val Arg Ser Lys Ile 
                405                 410                 415     


Ala Glu Tyr Met Asn His Leu Ile Asp Ile Gly Val Ala Gly Phe Arg 
            420                 425                 430         


Leu Asp Ala Ser Lys His Met Trp Pro Gly Asp Ile Lys Ala Ile Leu 
        435                 440                 445             


Asp Lys Leu His Asn Leu Asn Ser Asn Trp Phe Pro Ala Gly Ser Lys 
    450                 455                 460                 


Pro Phe Ile Tyr Gln Glu Val Ile Asp Leu Gly Gly Glu Pro Ile Lys 
465                 470                 475                 480 


Ser Ser Asp Tyr Phe Gly Asn Gly Arg Val Thr Glu Phe Lys Tyr Gly 
                485                 490                 495     


Ala Lys Leu Gly Thr Val Ile Arg Lys Trp Asn Gly Glu Lys Met Ser 
            500                 505                 510         


Tyr Leu Lys Asn Trp Gly Glu Gly Trp Gly Phe Val Pro Ser Asp Arg 
        515                 520                 525             


Ala Leu Val Phe Val Asp Asn His Asp Asn Gln Arg Gly His Gly Ala 
    530                 535                 540                 


Gly Gly Ala Ser Ile Leu Thr Phe Trp Asp Ala Arg Leu Tyr Lys Met 
545                 550                 555                 560 


Ala Val Gly Phe Met Leu Ala His Pro Tyr Gly Phe Thr Arg Val Met 
                565                 570                 575     


Ser Ser Tyr Arg Trp Pro Arg Gln Phe Gln Asn Gly Asn Asp Val Asn 
            580                 585                 590         


Asp Trp Val Gly Pro Pro Asn Asn Asn Gly Val Ile Lys Glu Val Thr 
        595                 600                 605             


Ile Asn Pro Asp Thr Thr Cys Gly Asn Asp Trp Val Cys Glu His Arg 
    610                 615                 620                 


Trp Arg Gln Ile Arg Asn Met Val Ile Phe Arg Asn Val Val Asp Gly 
625                 630                 635                 640 


Gln Pro Phe Thr Asn Trp Tyr Asp Asn Gly Ser Asn Gln Val Ala Phe 
                645                 650                 655     


Gly Arg Gly Asn Arg Gly Phe Ile Val Phe Asn Asn Asp Asp Trp Ser 
            660                 665                 670         


Phe Ser Leu Thr Leu Gln Thr Gly Leu Pro Ala Gly Thr Tyr Cys Asp 
        675                 680                 685             


Val Ile Ser Gly Asp Lys Ile Asn Gly Asn Cys Thr Gly Ile Lys Ile 
    690                 695                 700                 


Tyr Val Ser Asp Asp Gly Lys Ala His Phe Ser Ile Ser Asn Ser Ala 
705                 710                 715                 720 


Glu Asp Pro Phe Ile Ala Ile His Ala Glu Ser Lys Leu 
                725                 730             


<210>  44
<211>  511
<212>  PRT
<213>  Homo sapiens

<400>  44

Met Lys Leu Phe Trp Leu Leu Phe Thr Ile Gly Phe Cys Trp Ala Gln 
1               5                   10                  15      


Tyr Ser Ser Asn Thr Gln Gln Gly Arg Thr Ser Ile Val His Leu Phe 
            20                  25                  30          


Glu Trp Arg Trp Val Asp Ile Ala Leu Glu Cys Glu Arg Tyr Leu Ala 
        35                  40                  45              


Pro Lys Gly Phe Gly Gly Val Gln Val Ser Pro Pro Asn Glu Asn Val 
    50                  55                  60                  


Ala Ile His Asn Pro Phe Arg Pro Trp Trp Glu Arg Tyr Gln Pro Val 
65                  70                  75                  80  


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


Met Val Thr Arg Cys Asn Asn Val Gly Val Arg Ile Tyr Val Asp Ala 
            100                 105                 110         


Val Ile Asn His Met Cys Gly Asn Ala Val Ser Ala Gly Thr Ser Ser 
        115                 120                 125             


Thr Cys Gly Ser Tyr Phe Asn Pro Gly Ser Arg Asp Phe Pro Ala Val 
    130                 135                 140                 


Pro Tyr Ser Gly Trp Asp Phe Asn Asp Gly Lys Cys Lys Thr Gly Ser 
145                 150                 155                 160 


Gly Asp Ile Glu Asn Tyr Asn Asp Ala Thr Gln Val Arg Asp Cys Arg 
                165                 170                 175     


Leu Ser Gly Leu Leu Asp Leu Ala Leu Gly Lys Asp Tyr Val Arg Ser 
            180                 185                 190         


Lys Ile Ala Glu Tyr Met Asn His Leu Ile Asp Ile Gly Val Ala Gly 
        195                 200                 205             


Phe Arg Ile Asp Ala Ser Lys His Met Trp Pro Gly Asp Ile Lys Ala 
    210                 215                 220                 


Ile Leu Asp Lys Leu His Asn Leu Asn Ser Asn Trp Phe Pro Glu Gly 
225                 230                 235                 240 


Ser Lys Pro Phe Ile Tyr Gln Glu Val Ile Asp Leu Gly Gly Glu Pro 
                245                 250                 255     


Ile Lys Ser Ser Asp Tyr Phe Gly Asn Gly Arg Val Thr Glu Phe Lys 
            260                 265                 270         


Tyr Gly Ala Lys Leu Gly Thr Val Ile Arg Lys Trp Asn Gly Glu Lys 
        275                 280                 285             


Met Ser Tyr Leu Lys Asn Trp Gly Glu Gly Trp Gly Phe Met Pro Ser 
    290                 295                 300                 


Asp Arg Ala Leu Val Phe Val Asp Asn His Asp Asn Gln Arg Gly His 
305                 310                 315                 320 


Gly Ala Gly Gly Ala Ser Ile Leu Thr Phe Trp Asp Ala Arg Leu Tyr 
                325                 330                 335     


Lys Met Ala Val Gly Phe Met Leu Ala His Pro Tyr Gly Phe Thr Arg 
            340                 345                 350         


Val Met Ser Ser Tyr Arg Trp Pro Arg Tyr Phe Glu Asn Gly Lys Asp 
        355                 360                 365             


Val Asn Asp Trp Val Gly Pro Pro Asn Asp Asn Gly Val Thr Lys Glu 
    370                 375                 380                 


Val Thr Ile Asn Pro Asp Thr Thr Cys Gly Asn Asp Trp Val Cys Glu 
385                 390                 395                 400 


His Arg Trp Arg Gln Ile Arg Asn Met Val Asn Phe Arg Asn Val Val 
                405                 410                 415     


Asp Gly Gln Pro Phe Thr Asn Trp Tyr Asp Asn Gly Ser Asn Gln Val 
            420                 425                 430         


Ala Phe Gly Arg Gly Asn Arg Gly Phe Ile Val Phe Asn Asn Asp Asp 
        435                 440                 445             


Trp Thr Phe Ser Leu Thr Leu Gln Thr Gly Leu Pro Ala Gly Thr Tyr 
    450                 455                 460                 


Cys Asp Val Ile Ser Gly Asp Lys Ile Asn Gly Asn Cys Thr Gly Ile 
465                 470                 475                 480 


Lys Ile Tyr Val Ser Asp Asp Gly Lys Ala His Phe Ser Ile Ser Asn 
                485                 490                 495     


Ser Ala Glu Asp Pro Phe Ile Ala Ile His Ala Glu Ser Lys Leu 
            500                 505                 510     


<210>  45
<211>  952
<212>  PRT
<213>  Artificial

<220>
<223>  full-length, immature GAA amino acid sequence

<400>  45

Met Gly Val Arg His Pro Pro Cys Ser His Arg Leu Leu Ala Val Cys 
1               5                   10                  15      


Ala Leu Val Ser Leu Ala Thr Ala Ala Leu Leu Gly His Ile Leu Leu 
            20                  25                  30          


His Asp Phe Leu Leu Val Pro Arg Glu Leu Ser Gly Ser Ser Pro Val 
        35                  40                  45              


Leu Glu Glu Thr His Pro Ala His Gln Gln Gly Ala Ser Arg Pro Gly 
    50                  55                  60                  


Pro Arg Asp Ala Gln Ala His Pro Gly Arg Pro Arg Ala Val Pro Thr 
65                  70                  75                  80  


Gln Cys Asp Val Pro Pro Asn Ser Arg Phe Asp Cys Ala Pro Asp Lys 
                85                  90                  95      


Ala Ile Thr Gln Glu Gln Cys Glu Ala Arg Gly Cys Cys Tyr Ile Pro 
            100                 105                 110         


Ala Lys Gln Gly Leu Gln Gly Ala Gln Met Gly Gln Pro Trp Cys Phe 
        115                 120                 125             


Phe Pro Pro Ser Tyr Pro Ser Tyr Lys Leu Glu Asn Leu Ser Ser Ser 
    130                 135                 140                 


Glu Met Gly Tyr Thr Ala Thr Leu Thr Arg Thr Thr Pro Thr Phe Phe 
145                 150                 155                 160 


Pro Lys Asp Ile Leu Thr Leu Arg Leu Asp Val Met Met Glu Thr Glu 
                165                 170                 175     


Asn Arg Leu His Phe Thr Ile Lys Asp Pro Ala Asn Arg Arg Tyr Glu 
            180                 185                 190         


Val Pro Leu Glu Thr Pro His Val His Ser Arg Ala Pro Ser Pro Leu 
        195                 200                 205             


Tyr Ser Val Glu Phe Ser Glu Glu Pro Phe Gly Val Ile Val Arg Arg 
    210                 215                 220                 


Gln Leu Asp Gly Arg Val Leu Leu Asn Thr Thr Val Ala Pro Leu Phe 
225                 230                 235                 240 


Phe Ala Asp Gln Phe Leu Gln Leu Ser Thr Ser Leu Pro Ser Gln Tyr 
                245                 250                 255     


Ile Thr Gly Leu Ala Glu His Leu Ser Pro Leu Met Leu Ser Thr Ser 
            260                 265                 270         


Trp Thr Arg Ile Thr Leu Trp Asn Arg Asp Leu Ala Pro Thr Pro Gly 
        275                 280                 285             


Ala Asn Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala Leu Glu Asp Gly 
    290                 295                 300                 


Gly Ser Ala His Gly Val Phe Leu Leu Asn Ser Asn Ala Met Asp Val 
305                 310                 315                 320 


Val Leu Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser Thr Gly Gly Ile 
                325                 330                 335     


Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys Ser Val Val Gln 
            340                 345                 350         


Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe Met Pro Pro Tyr Trp Gly 
        355                 360                 365             


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


Arg Gln Val Val Glu Asn Met Thr Arg Ala His Phe Pro Leu Asp Val 
385                 390                 395                 400 


Gln Trp Asn Asp Leu Asp Tyr Met Asp Ser Arg Arg Asp Phe Thr Phe 
                405                 410                 415     


Asn Lys Asp Gly Phe Arg Asp Phe Pro Ala Met Val Gln Glu Leu His 
            420                 425                 430         


Gln Gly Gly Arg Arg Tyr Met Met Ile Val Asp Pro Ala Ile Ser Ser 
        435                 440                 445             


Ser Gly Pro Ala Gly Ser Tyr Arg Pro Tyr Asp Glu Gly Leu Arg Arg 
    450                 455                 460                 


Gly Val Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu Ile Gly Lys Val 
465                 470                 475                 480 


Trp Pro Gly Ser Thr Ala Phe Pro Asp Phe Thr Asn Pro Thr Ala Leu 
                485                 490                 495     


Ala Trp Trp Glu Asp Met Val Ala Glu Phe His Asp Gln Val Pro Phe 
            500                 505                 510         


Asp Gly Met Trp Ile Asp Met Asn Glu Pro Ser Asn Phe Ile Arg Gly 
        515                 520                 525             


Ser Glu Asp Gly Cys Pro Asn Asn Glu Leu Glu Asn Pro Pro Tyr Val 
    530                 535                 540                 


Pro Gly Val Val Gly Gly Thr Leu Gln Ala Ala Thr Ile Cys Ala Ser 
545                 550                 555                 560 


Ser His Gln Phe Leu Ser Thr His Tyr Asn Leu His Asn Leu Tyr Gly 
                565                 570                 575     


Leu Thr Glu Ala Ile Ala Ser His Arg Ala Leu Val Lys Ala Arg Gly 
            580                 585                 590         


Thr Arg Pro Phe Val Ile Ser Arg Ser Thr Phe Ala Gly His Gly Arg 
        595                 600                 605             


Tyr Ala Gly His Trp Thr Gly Asp Val Trp Ser Ser Trp Glu Gln Leu 
    610                 615                 620                 


Ala Ser Ser Val Pro Glu Ile Leu Gln Phe Asn Leu Leu Gly Val Pro 
625                 630                 635                 640 


Leu Val Gly Ala Asp Val Cys Gly Phe Leu Gly Asn Thr Ser Glu Glu 
                645                 650                 655     


Leu Cys Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr Pro Phe Met Arg 
            660                 665                 670         


Asn His Asn Ser Leu Leu Ser Leu Pro Gln Glu Pro Tyr Ser Phe Ser 
        675                 680                 685             


Glu Pro Ala Gln Gln Ala Met Arg Lys Ala Leu Thr Leu Arg Tyr Ala 
    690                 695                 700                 


Leu Leu Pro His Leu Tyr Thr Leu Phe His Gln Ala His Val Ala Gly 
705                 710                 715                 720 


Glu Thr Val Ala Arg Pro Leu Phe Leu Glu Phe Pro Lys Asp Ser Ser 
                725                 730                 735     


Thr Trp Thr Val Asp His Gln Leu Leu Trp Gly Glu Ala Leu Leu Ile 
            740                 745                 750         


Thr Pro Val Leu Gln Ala Gly Lys Ala Glu Val Thr Gly Tyr Phe Pro 
        755                 760                 765             


Leu Gly Thr Trp Tyr Asp Leu Gln Thr Val Pro Val Glu Ala Leu Gly 
    770                 775                 780                 


Ser Leu Pro Pro Pro Pro Ala Ala Pro Arg Glu Pro Ala Ile His Ser 
785                 790                 795                 800 


Glu Gly Gln Trp Val Thr Leu Pro Ala Pro Leu Asp Thr Ile Asn Val 
                805                 810                 815     


His Leu Arg Ala Gly Tyr Ile Ile Pro Leu Gln Gly Pro Gly Leu Thr 
            820                 825                 830         


Thr Thr Glu Ser Arg Gln Gln Pro Met Ala Leu Ala Val Ala Leu Thr 
        835                 840                 845             


Lys Gly Gly Glu Ala Arg Gly Glu Leu Phe Trp Asp Asp Gly Glu Ser 
    850                 855                 860                 


Leu Glu Val Leu Glu Arg Gly Ala Tyr Thr Gln Val Ile Phe Leu Ala 
865                 870                 875                 880 


Arg Asn Asn Thr Ile Val Asn Glu Leu Val Arg Val Thr Ser Glu Gly 
                885                 890                 895     


Ala Gly Leu Gln Leu Gln Lys Val Thr Val Leu Gly Val Ala Thr Ala 
            900                 905                 910         


Pro Gln Gln Val Leu Ser Asn Gly Val Pro Val Ser Asn Phe Thr Tyr 
        915                 920                 925             


Ser Pro Asp Thr Lys Val Leu Asp Ile Cys Val Ser Leu Leu Met Gly 
    930                 935                 940                 


Glu Gln Phe Leu Val Ser Trp Cys 
945                 950         


<210>  46
<211>  957
<212>  PRT
<213>  Artificial

<220>
<223>  full-length, immature GAA amino acid sequence

<400>  46

Met Gly Val Arg His Pro Pro Cys Ser His Arg Leu Leu Ala Val Cys 
1               5                   10                  15      


Ala Leu Val Ser Leu Ala Thr Ala Ala Leu Leu Gly His Ile Leu Leu 
            20                  25                  30          


His Asp Phe Leu Leu Val Pro Arg Glu Leu Ser Gly Ser Ser Pro Val 
        35                  40                  45              


Leu Glu Glu Thr His Pro Ala His Gln Gln Gly Ala Ser Arg Pro Gly 
    50                  55                  60                  


Pro Arg Asp Ala Gln Ala His Pro Gly Arg Pro Arg Ala Val Pro Thr 
65                  70                  75                  80  


Gln Cys Asp Val Pro Pro Asn Ser Arg Phe Asp Cys Ala Pro Asp Lys 
                85                  90                  95      


Ala Ile Thr Gln Glu Gln Cys Glu Ala Arg Gly Cys Cys Tyr Ile Pro 
            100                 105                 110         


Ala Lys Gln Gly Leu Gln Gly Ala Gln Met Gly Gln Pro Trp Cys Phe 
        115                 120                 125             


Phe Pro Pro Ser Tyr Pro Ser Tyr Lys Leu Glu Asn Leu Ser Ser Ser 
    130                 135                 140                 


Glu Met Gly Tyr Thr Ala Thr Leu Thr Arg Thr Thr Pro Thr Phe Phe 
145                 150                 155                 160 


Pro Lys Asp Ile Leu Thr Leu Arg Leu Asp Val Met Met Glu Thr Glu 
                165                 170                 175     


Asn Arg Leu His Phe Thr Ile Lys Asp Pro Ala Asn Arg Arg Tyr Glu 
            180                 185                 190         


Val Pro Leu Glu Thr Pro His Val His Ser Arg Ala Pro Ser Pro Leu 
        195                 200                 205             


Tyr Ser Val Glu Phe Ser Glu Glu Pro Phe Gly Val Ile Val Arg Arg 
    210                 215                 220                 


Gln Leu Asp Gly Arg Val Leu Leu Asn Thr Thr Val Ala Pro Leu Phe 
225                 230                 235                 240 


Phe Ala Asp Gln Phe Leu Gln Leu Ser Thr Ser Leu Pro Ser Gln Tyr 
                245                 250                 255     


Ile Thr Gly Leu Ala Glu His Leu Ser Pro Leu Met Leu Ser Thr Ser 
            260                 265                 270         


Trp Thr Arg Ile Thr Leu Trp Asn Arg Asp Leu Ala Pro Thr Pro Gly 
        275                 280                 285             


Ala Asn Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala Leu Glu Asp Gly 
    290                 295                 300                 


Gly Ser Ala His Gly Val Phe Leu Leu Asn Ser Asn Ala Met Asp Val 
305                 310                 315                 320 


Val Leu Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser Thr Gly Gly Ile 
                325                 330                 335     


Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys Ser Val Val Gln 
            340                 345                 350         


Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe Met Pro Pro Tyr Trp Gly 
        355                 360                 365             


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


Arg Gln Val Val Glu Asn Met Thr Arg Ala His Phe Pro Leu Asp Val 
385                 390                 395                 400 


Gln Trp Asn Asp Leu Asp Tyr Met Asp Ser Arg Arg Asp Phe Thr Phe 
                405                 410                 415     


Asn Lys Asp Gly Phe Arg Asp Phe Pro Ala Met Val Gln Glu Leu His 
            420                 425                 430         


Gln Gly Gly Arg Arg Tyr Met Met Ile Val Asp Pro Ala Ile Ser Ser 
        435                 440                 445             


Ser Gly Pro Ala Gly Ser Tyr Arg Pro Tyr Asp Glu Gly Leu Arg Arg 
    450                 455                 460                 


Gly Val Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu Ile Gly Lys Val 
465                 470                 475                 480 


Trp Pro Gly Ser Thr Ala Phe Pro Asp Phe Thr Asn Pro Thr Ala Leu 
                485                 490                 495     


Ala Trp Trp Glu Asp Met Val Ala Glu Phe His Asp Gln Val Pro Phe 
            500                 505                 510         


Asp Gly Met Trp Ile Asp Met Asn Glu Pro Ser Asn Phe Ile Arg Gly 
        515                 520                 525             


Ser Glu Asp Gly Cys Pro Asn Asn Glu Leu Glu Asn Pro Pro Tyr Val 
    530                 535                 540                 


Pro Gly Val Val Gly Gly Thr Leu Gln Ala Ala Thr Ile Cys Ala Ser 
545                 550                 555                 560 


Ser His Gln Phe Leu Ser Thr His Tyr Asn Leu His Asn Leu Tyr Gly 
                565                 570                 575     


Leu Thr Glu Ala Ile Ala Ser His Arg Ala Leu Val Lys Ala Arg Gly 
            580                 585                 590         


Thr Arg Pro Phe Val Ile Ser Arg Ser Thr Phe Ala Gly His Gly Arg 
        595                 600                 605             


Tyr Ala Gly His Trp Thr Gly Asp Val Trp Ser Ser Trp Glu Gln Leu 
    610                 615                 620                 


Ala Ser Ser Val Pro Glu Ile Leu Gln Phe Asn Leu Leu Gly Val Pro 
625                 630                 635                 640 


Leu Val Gly Ala Asp Val Cys Gly Phe Leu Gly Asn Thr Ser Glu Glu 
                645                 650                 655     


Leu Cys Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr Pro Phe Met Arg 
            660                 665                 670         


Asn His Asn Ser Leu Leu Ser Leu Pro Gln Glu Pro Tyr Ser Phe Ser 
        675                 680                 685             


Glu Pro Ala Gln Gln Ala Met Arg Lys Ala Leu Thr Leu Arg Tyr Ala 
    690                 695                 700                 


Leu Leu Pro His Leu Tyr Thr Leu Phe His Gln Ala His Val Ala Gly 
705                 710                 715                 720 


Glu Thr Val Ala Arg Pro Leu Phe Leu Glu Phe Pro Lys Asp Ser Ser 
                725                 730                 735     


Thr Trp Thr Val Asp His Gln Leu Leu Trp Gly Glu Ala Leu Leu Ile 
            740                 745                 750         


Thr Pro Val Leu Gln Ala Gly Lys Ala Glu Val Thr Gly Tyr Phe Pro 
        755                 760                 765             


Leu Gly Thr Trp Tyr Asp Leu Gln Thr Val Pro Ile Glu Ala Leu Gly 
    770                 775                 780                 


Ser Leu Pro Pro Pro Pro Ala Ala Pro Arg Glu Pro Ala Ile His Ser 
785                 790                 795                 800 


Glu Gly Gln Trp Val Thr Leu Pro Ala Pro Leu Asp Thr Ile Asn Val 
                805                 810                 815     


His Leu Arg Ala Gly Tyr Ile Ile Pro Leu Gln Gly Pro Gly Leu Thr 
            820                 825                 830         


Thr Thr Glu Ser Arg Gln Gln Pro Met Ala Leu Ala Val Ala Leu Thr 
        835                 840                 845             


Lys Gly Gly Glu Ala Arg Gly Glu Leu Phe Trp Asp Asp Gly Glu Ser 
    850                 855                 860                 


Leu Glu Val Leu Glu Arg Gly Ala Tyr Thr Gln Val Ile Phe Leu Ala 
865                 870                 875                 880 


Arg Asn Asn Thr Ile Val Asn Glu Leu Val Arg Val Thr Ser Glu Gly 
                885                 890                 895     


Ala Gly Leu Gln Leu Gln Lys Val Thr Val Leu Gly Val Ala Thr Ala 
            900                 905                 910         


Pro Gln Gln Val Leu Ser Asn Gly Val Pro Val Ser Asn Phe Thr Tyr 
        915                 920                 925             


Ser Pro Asp Thr Lys Ala Arg Gly Pro Arg Val Leu Asp Ile Cys Val 
    930                 935                 940                 


Ser Leu Leu Met Gly Glu Gln Phe Leu Val Ser Trp Cys 
945                 950                 955         


<210>  47
<211>  660
<212>  PRT
<213>  Artificial

<220>
<223>  mature GAA amino acid sequence

<400>  47

Gly Gln Pro Trp Cys Phe Phe Pro Pro Ser Tyr Pro Ser Tyr Lys Leu 
1               5                   10                  15      


Glu Asn Leu Ser Ser Ser Glu Met Gly Tyr Thr Ala Thr Leu Thr Arg 
            20                  25                  30          


Thr Thr Pro Thr Phe Phe Pro Lys Asp Ile Leu Thr Leu Arg Leu Asp 
        35                  40                  45              


Val Met Met Glu Thr Glu Asn Arg Leu His Phe Thr Ile Lys Asp Pro 
    50                  55                  60                  


Ala Asn Arg Arg Tyr Glu Val Pro Leu Glu Thr Pro His Val His Ser 
65                  70                  75                  80  


Arg Ala Pro Ser Pro Leu Tyr Ser Val Glu Phe Ser Glu Glu Pro Phe 
                85                  90                  95      


Gly Val Ile Val Arg Arg Gln Leu Asp Gly Arg Val Leu Leu Asn Thr 
            100                 105                 110         


Thr Val Ala Pro Leu Phe Phe Ala Asp Gln Phe Leu Gln Leu Ser Thr 
        115                 120                 125             


Ser Leu Pro Ser Gln Tyr Ile Thr Gly Leu Ala Glu His Leu Ser Pro 
    130                 135                 140                 


Leu Met Leu Ser Thr Ser Trp Thr Arg Ile Thr Leu Trp Asn Arg Asp 
145                 150                 155                 160 


Leu Ala Pro Thr Pro Gly Ala Asn Leu Tyr Gly Ser His Pro Phe Tyr 
                165                 170                 175     


Leu Ala Leu Glu Asp Gly Gly Ser Ala His Gly Val Phe Leu Leu Asn 
            180                 185                 190         


Ser Asn Ala Met Asp Val Val Leu Gln Pro Ser Pro Ala Leu Ser Trp 
        195                 200                 205             


Arg Ser Thr Gly Gly Ile Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu 
    210                 215                 220                 


Pro Lys Ser Val Val Gln Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe 
225                 230                 235                 240 


Met Pro Pro Tyr Trp Gly Leu Gly Phe His Leu Cys Arg Trp Gly Tyr 
                245                 250                 255     


Ser Ser Thr Ala Ile Thr Arg Gln Val Val Glu Asn Met Thr Arg Ala 
            260                 265                 270         


His Phe Pro Leu Asp Val Gln Trp Asn Asp Leu Asp Tyr Met Asp Ser 
        275                 280                 285             


Arg Arg Asp Phe Thr Phe Asn Lys Asp Gly Phe Arg Asp Phe Pro Ala 
    290                 295                 300                 


Met Val Gln Glu Leu His Gln Gly Gly Arg Arg Tyr Met Met Ile Val 
305                 310                 315                 320 


Asp Pro Ala Ile Ser Ser Ser Gly Pro Ala Gly Ser Tyr Arg Pro Tyr 
                325                 330                 335     


Asp Glu Gly Leu Arg Arg Gly Val Phe Ile Thr Asn Glu Thr Gly Gln 
            340                 345                 350         


Pro Leu Ile Gly Lys Val Trp Pro Gly Ser Thr Ala Phe Pro Asp Phe 
        355                 360                 365             


Thr Asn Pro Thr Ala Leu Ala Trp Trp Glu Asp Met Val Ala Glu Phe 
    370                 375                 380                 


His Asp Gln Val Pro Phe Asp Gly Met Trp Ile Asp Met Asn Glu Pro 
385                 390                 395                 400 


Ser Asn Phe Ile Arg Gly Ser Glu Asp Gly Cys Pro Asn Asn Glu Leu 
                405                 410                 415     


Glu Asn Pro Pro Tyr Val Pro Gly Val Val Gly Gly Thr Leu Gln Ala 
            420                 425                 430         


Ala Thr Ile Cys Ala Ser Ser His Gln Phe Leu Ser Thr His Tyr Asn 
        435                 440                 445             


Leu His Asn Leu Tyr Gly Leu Thr Glu Ala Ile Ala Ser His Arg Ala 
    450                 455                 460                 


Leu Val Lys Ala Arg Gly Thr Arg Pro Phe Val Ile Ser Arg Ser Thr 
465                 470                 475                 480 


Phe Ala Gly His Gly Arg Tyr Ala Gly His Trp Thr Gly Asp Val Trp 
                485                 490                 495     


Ser Ser Trp Glu Gln Leu Ala Ser Ser Val Pro Glu Ile Leu Gln Phe 
            500                 505                 510         


Asn Leu Leu Gly Val Pro Leu Val Gly Ala Asp Val Cys Gly Phe Leu 
        515                 520                 525             


Gly Asn Thr Ser Glu Glu Leu Cys Val Arg Trp Thr Gln Leu Gly Ala 
    530                 535                 540                 


Phe Tyr Pro Phe Met Arg Asn His Asn Ser Leu Leu Ser Leu Pro Gln 
545                 550                 555                 560 


Glu Pro Tyr Ser Phe Ser Glu Pro Ala Gln Gln Ala Met Arg Lys Ala 
                565                 570                 575     


Leu Thr Leu Arg Tyr Ala Leu Leu Pro His Leu Tyr Thr Leu Phe His 
            580                 585                 590         


Gln Ala His Val Ala Gly Glu Thr Val Ala Arg Pro Leu Phe Leu Glu 
        595                 600                 605             


Phe Pro Lys Asp Ser Ser Thr Trp Thr Val Asp His Gln Leu Leu Trp 
    610                 615                 620                 


Gly Glu Ala Leu Leu Ile Thr Pro Val Leu Gln Ala Gly Lys Ala Glu 
625                 630                 635                 640 


Val Thr Gly Tyr Phe Pro Leu Gly Thr Trp Tyr Asp Leu Gln Thr Val 
                645                 650                 655     


Pro Val Glu Ala 
            660 


<210>  48
<211>  495
<212>  PRT
<213>  Artificial

<220>
<223>  mature GAA amino acid sequence

<400>  48

Gly Ala Asn Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala Leu Glu Asp 
1               5                   10                  15      


Gly Gly Ser Ala His Gly Val Phe Leu Leu Asn Ser Asn Ala Met Asp 
            20                  25                  30          


Val Val Leu Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser Thr Gly Gly 
        35                  40                  45              


Ile Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys Ser Val Val 
    50                  55                  60                  


Gln Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe Met Pro Pro Tyr Trp 
65                  70                  75                  80  


Gly Leu Gly Phe His Leu Cys Arg Trp Gly Tyr Ser Ser Thr Ala Ile 
                85                  90                  95      


Thr Arg Gln Val Val Glu Asn Met Thr Arg Ala His Phe Pro Leu Asp 
            100                 105                 110         


Val Gln Trp Asn Asp Leu Asp Tyr Met Asp Ser Arg Arg Asp Phe Thr 
        115                 120                 125             


Phe Asn Lys Asp Gly Phe Arg Asp Phe Pro Ala Met Val Gln Glu Leu 
    130                 135                 140                 


His Gln Gly Gly Arg Arg Tyr Met Met Ile Val Asp Pro Ala Ile Ser 
145                 150                 155                 160 


Ser Ser Gly Pro Ala Gly Ser Tyr Arg Pro Tyr Asp Glu Gly Leu Arg 
                165                 170                 175     


Arg Gly Val Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu Ile Gly Lys 
            180                 185                 190         


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


Leu Ala Trp Trp Glu Asp Met Val Ala Glu Phe His Asp Gln Val Pro 
    210                 215                 220                 


Phe Asp Gly Met Trp Ile Asp Met Asn Glu Pro Ser Asn Phe Ile Arg 
225                 230                 235                 240 


Gly Ser Glu Asp Gly Cys Pro Asn Asn Glu Leu Glu Asn Pro Pro Tyr 
                245                 250                 255     


Val Pro Gly Val Val Gly Gly Thr Leu Gln Ala Ala Thr Ile Cys Ala 
            260                 265                 270         


Ser Ser His Gln Phe Leu Ser Thr His Tyr Asn Leu His Asn Leu Tyr 
        275                 280                 285             


Gly Leu Thr Glu Ala Ile Ala Ser His Arg Ala Leu Val Lys Ala Arg 
    290                 295                 300                 


Gly Thr Arg Pro Phe Val Ile Ser Arg Ser Thr Phe Ala Gly His Gly 
305                 310                 315                 320 


Arg Tyr Ala Gly His Trp Thr Gly Asp Val Trp Ser Ser Trp Glu Gln 
                325                 330                 335     


Leu Ala Ser Ser Val Pro Glu Ile Leu Gln Phe Asn Leu Leu Gly Val 
            340                 345                 350         


Pro Leu Val Gly Ala Asp Val Cys Gly Phe Leu Gly Asn Thr Ser Glu 
        355                 360                 365             


Glu Leu Cys Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr Pro Phe Met 
    370                 375                 380                 


Arg Asn His Asn Ser Leu Leu Ser Leu Pro Gln Glu Pro Tyr Ser Phe 
385                 390                 395                 400 


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


Ala Leu Leu Pro His Leu Tyr Thr Leu Phe His Gln Ala His Val Ala 
            420                 425                 430         


Gly Glu Thr Val Ala Arg Pro Leu Phe Leu Glu Phe Pro Lys Asp Ser 
        435                 440                 445             


Ser Thr Trp Thr Val Asp His Gln Leu Leu Trp Gly Glu Ala Leu Leu 
    450                 455                 460                 


Ile Thr Pro Val Leu Gln Ala Gly Lys Ala Glu Val Thr Gly Tyr Phe 
465                 470                 475                 480 


Pro Leu Gly Thr Trp Tyr Asp Leu Gln Thr Val Pro Val Glu Ala 
                485                 490                 495 


<210>  49
<211>  892
<212>  PRT
<213>  Artificial

<220>
<223>  mature GAA amino acid sequence

<400>  49

Ser Arg Pro Gly Pro Arg Asp Ala Gln Ala His Pro Gly Arg Pro Arg 
1               5                   10                  15      


Ala Val Pro Thr Gln Cys Asp Val Pro Pro Asn Ser Arg Phe Asp Cys 
            20                  25                  30          


Ala Pro Asp Lys Ala Ile Thr Gln Glu Gln Cys Glu Ala Arg Gly Cys 
        35                  40                  45              


Cys Tyr Ile Pro Ala Lys Gln Gly Leu Gln Gly Ala Gln Met Gly Gln 
    50                  55                  60                  


Pro Trp Cys Phe Phe Pro Pro Ser Tyr Pro Ser Tyr Lys Leu Glu Asn 
65                  70                  75                  80  


Leu Ser Ser Ser Glu Met Gly Tyr Thr Ala Thr Leu Thr Arg Thr Thr 
                85                  90                  95      


Pro Thr Phe Phe Pro Lys Asp Ile Leu Thr Leu Arg Leu Asp Val Met 
            100                 105                 110         


Met Glu Thr Glu Asn Arg Leu His Phe Thr Ile Lys Asp Pro Ala Asn 
        115                 120                 125             


Arg Arg Tyr Glu Val Pro Leu Glu Thr Pro His Val His Ser Arg Ala 
    130                 135                 140                 


Pro Ser Pro Leu Tyr Ser Val Glu Phe Ser Glu Glu Pro Phe Gly Val 
145                 150                 155                 160 


Ile Val Arg Arg Gln Leu Asp Gly Arg Val Leu Leu Asn Thr Thr Val 
                165                 170                 175     


Ala Pro Leu Phe Phe Ala Asp Gln Phe Leu Gln Leu Ser Thr Ser Leu 
            180                 185                 190         


Pro Ser Gln Tyr Ile Thr Gly Leu Ala Glu His Leu Ser Pro Leu Met 
        195                 200                 205             


Leu Ser Thr Ser Trp Thr Arg Ile Thr Leu Trp Asn Arg Asp Leu Ala 
    210                 215                 220                 


Pro Thr Pro Gly Ala Asn Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala 
225                 230                 235                 240 


Leu Glu Asp Gly Gly Ser Ala His Gly Val Phe Leu Leu Asn Ser Asn 
                245                 250                 255     


Ala Met Asp Val Val Leu Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser 
            260                 265                 270         


Thr Gly Gly Ile Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys 
        275                 280                 285             


Ser Val Val Gln Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe Met Pro 
    290                 295                 300                 


Pro Tyr Trp Gly Leu Gly Phe His Leu Cys Arg Trp Gly Tyr Ser Ser 
305                 310                 315                 320 


Thr Ala Ile Thr Arg Gln Val Val Glu Asn Met Thr Arg Ala His Phe 
                325                 330                 335     


Pro Leu Asp Val Gln Trp Asn Asp Leu Asp Tyr Met Asp Ser Arg Arg 
            340                 345                 350         


Asp Phe Thr Phe Asn Lys Asp Gly Phe Arg Asp Phe Pro Ala Met Val 
        355                 360                 365             


Gln Glu Leu His Gln Gly Gly Arg Arg Tyr Met Met Ile Val Asp Pro 
    370                 375                 380                 


Ala Ile Ser Ser Ser Gly Pro Ala Gly Ser Tyr Arg Pro Tyr Asp Glu 
385                 390                 395                 400 


Gly Leu Arg Arg Gly Val Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu 
                405                 410                 415     


Ile Gly Lys Val Trp Pro Gly Ser Thr Ala Phe Pro Asp Phe Thr Asn 
            420                 425                 430         


Pro Thr Ala Leu Ala Trp Trp Glu Asp Met Val Ala Glu Phe His Asp 
        435                 440                 445             


Gln Val Pro Phe Asp Gly Met Trp Ile Asp Met Asn Glu Pro Ser Asn 
    450                 455                 460                 


Phe Ile Arg Gly Ser Glu Asp Gly Cys Pro Asn Asn Glu Leu Glu Asn 
465                 470                 475                 480 


Pro Pro Tyr Val Pro Gly Val Val Gly Gly Thr Leu Gln Ala Ala Thr 
                485                 490                 495     


Ile Cys Ala Ser Ser His Gln Phe Leu Ser Thr His Tyr Asn Leu His 
            500                 505                 510         


Asn Leu Tyr Gly Leu Thr Glu Ala Ile Ala Ser His Arg Ala Leu Val 
        515                 520                 525             


Lys Ala Arg Gly Thr Arg Pro Phe Val Ile Ser Arg Ser Thr Phe Ala 
    530                 535                 540                 


Gly His Gly Arg Tyr Ala Gly His Trp Thr Gly Asp Val Trp Ser Ser 
545                 550                 555                 560 


Trp Glu Gln Leu Ala Ser Ser Val Pro Glu Ile Leu Gln Phe Asn Leu 
                565                 570                 575     


Leu Gly Val Pro Leu Val Gly Ala Asp Val Cys Gly Phe Leu Gly Asn 
            580                 585                 590         


Thr Ser Glu Glu Leu Cys Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr 
        595                 600                 605             


Pro Phe Met Arg Asn His Asn Ser Leu Leu Ser Leu Pro Gln Glu Pro 
    610                 615                 620                 


Tyr Ser Phe Ser Glu Pro Ala Gln Gln Ala Met Arg Lys Ala Leu Thr 
625                 630                 635                 640 


Leu Arg Tyr Ala Leu Leu Pro His Leu Tyr Thr Leu Phe His Gln Ala 
                645                 650                 655     


His Val Ala Gly Glu Thr Val Ala Arg Pro Leu Phe Leu Glu Phe Pro 
            660                 665                 670         


Lys Asp Ser Ser Thr Trp Thr Val Asp His Gln Leu Leu Trp Gly Glu 
        675                 680                 685             


Ala Leu Leu Ile Thr Pro Val Leu Gln Ala Gly Lys Ala Glu Val Thr 
    690                 695                 700                 


Gly Tyr Phe Pro Leu Gly Thr Trp Tyr Asp Leu Gln Thr Val Pro Val 
705                 710                 715                 720 


Glu Ala Leu Gly Ser Leu Pro Pro Pro Pro Ala Ala Pro Arg Glu Pro 
                725                 730                 735     


Ala Ile His Ser Glu Gly Gln Trp Val Thr Leu Pro Ala Pro Leu Asp 
            740                 745                 750         


Thr Ile Asn Val His Leu Arg Ala Gly Tyr Ile Ile Pro Leu Gln Gly 
        755                 760                 765             


Pro Gly Leu Thr Thr Thr Glu Ser Arg Gln Gln Pro Met Ala Leu Ala 
    770                 775                 780                 


Val Ala Leu Thr Lys Gly Gly Glu Ala Arg Gly Glu Leu Phe Trp Asp 
785                 790                 795                 800 


Asp Gly Glu Ser Leu Glu Val Leu Glu Arg Gly Ala Tyr Thr Gln Val 
                805                 810                 815     


Ile Phe Leu Ala Arg Asn Asn Thr Ile Val Asn Glu Leu Val Arg Val 
            820                 825                 830         


Thr Ser Glu Gly Ala Gly Leu Gln Leu Gln Lys Val Thr Val Leu Gly 
        835                 840                 845             


Val Ala Thr Ala Pro Gln Gln Val Leu Ser Asn Gly Val Pro Val Ser 
    850                 855                 860                 


Asn Phe Thr Tyr Ser Pro Asp Thr Lys Val Leu Asp Ile Cys Val Ser 
865                 870                 875                 880 


Leu Leu Met Gly Glu Gln Phe Leu Val Ser Trp Cys 
                885                 890         


<210>  50
<211>  886
<212>  PRT
<213>  Artificial

<220>
<223>  mature GAA amino acid sequence

<400>  50

Asp Ala Gln Ala His Pro Gly Arg Pro Arg Ala Val Pro Thr Gln Cys 
1               5                   10                  15      


Asp Val Pro Pro Asn Ser Arg Phe Asp Cys Ala Pro Asp Lys Ala Ile 
            20                  25                  30          


Thr Gln Glu Gln Cys Glu Ala Arg Gly Cys Cys Tyr Ile Pro Ala Lys 
        35                  40                  45              


Gln Gly Leu Gln Gly Ala Gln Met Gly Gln Pro Trp Cys Phe Phe Pro 
    50                  55                  60                  


Pro Ser Tyr Pro Ser Tyr Lys Leu Glu Asn Leu Ser Ser Ser Glu Met 
65                  70                  75                  80  


Gly Tyr Thr Ala Thr Leu Thr Arg Thr Thr Pro Thr Phe Phe Pro Lys 
                85                  90                  95      


Asp Ile Leu Thr Leu Arg Leu Asp Val Met Met Glu Thr Glu Asn Arg 
            100                 105                 110         


Leu His Phe Thr Ile Lys Asp Pro Ala Asn Arg Arg Tyr Glu Val Pro 
        115                 120                 125             


Leu Glu Thr Pro His Val His Ser Arg Ala Pro Ser Pro Leu Tyr Ser 
    130                 135                 140                 


Val Glu Phe Ser Glu Glu Pro Phe Gly Val Ile Val Arg Arg Gln Leu 
145                 150                 155                 160 


Asp Gly Arg Val Leu Leu Asn Thr Thr Val Ala Pro Leu Phe Phe Ala 
                165                 170                 175     


Asp Gln Phe Leu Gln Leu Ser Thr Ser Leu Pro Ser Gln Tyr Ile Thr 
            180                 185                 190         


Gly Leu Ala Glu His Leu Ser Pro Leu Met Leu Ser Thr Ser Trp Thr 
        195                 200                 205             


Arg Ile Thr Leu Trp Asn Arg Asp Leu Ala Pro Thr Pro Gly Ala Asn 
    210                 215                 220                 


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


Ala His Gly Val Phe Leu Leu Asn Ser Asn Ala Met Asp Val Val Leu 
                245                 250                 255     


Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser Thr Gly Gly Ile Leu Asp 
            260                 265                 270         


Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys Ser Val Val Gln Gln Tyr 
        275                 280                 285             


Leu Asp Val Val Gly Tyr Pro Phe Met Pro Pro Tyr Trp Gly Leu Gly 
    290                 295                 300                 


Phe His Leu Cys Arg Trp Gly Tyr Ser Ser Thr Ala Ile Thr Arg Gln 
305                 310                 315                 320 


Val Val Glu Asn Met Thr Arg Ala His Phe Pro Leu Asp Val Gln Trp 
                325                 330                 335     


Asn Asp Leu Asp Tyr Met Asp Ser Arg Arg Asp Phe Thr Phe Asn Lys 
            340                 345                 350         


Asp Gly Phe Arg Asp Phe Pro Ala Met Val Gln Glu Leu His Gln Gly 
        355                 360                 365             


Gly Arg Arg Tyr Met Met Ile Val Asp Pro Ala Ile Ser Ser Ser Gly 
    370                 375                 380                 


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


Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu Ile Gly Lys Val Trp Pro 
                405                 410                 415     


Gly Ser Thr Ala Phe Pro Asp Phe Thr Asn Pro Thr Ala Leu Ala Trp 
            420                 425                 430         


Trp Glu Asp Met Val Ala Glu Phe His Asp Gln Val Pro Phe Asp Gly 
        435                 440                 445             


Met Trp Ile Asp Met Asn Glu Pro Ser Asn Phe Ile Arg Gly Ser Glu 
    450                 455                 460                 


Asp Gly Cys Pro Asn Asn Glu Leu Glu Asn Pro Pro Tyr Val Pro Gly 
465                 470                 475                 480 


Val Val Gly Gly Thr Leu Gln Ala Ala Thr Ile Cys Ala Ser Ser His 
                485                 490                 495     


Gln Phe Leu Ser Thr His Tyr Asn Leu His Asn Leu Tyr Gly Leu Thr 
            500                 505                 510         


Glu Ala Ile Ala Ser His Arg Ala Leu Val Lys Ala Arg Gly Thr Arg 
        515                 520                 525             


Pro Phe Val Ile Ser Arg Ser Thr Phe Ala Gly His Gly Arg Tyr Ala 
    530                 535                 540                 


Gly His Trp Thr Gly Asp Val Trp Ser Ser Trp Glu Gln Leu Ala Ser 
545                 550                 555                 560 


Ser Val Pro Glu Ile Leu Gln Phe Asn Leu Leu Gly Val Pro Leu Val 
                565                 570                 575     


Gly Ala Asp Val Cys Gly Phe Leu Gly Asn Thr Ser Glu Glu Leu Cys 
            580                 585                 590         


Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr Pro Phe Met Arg Asn His 
        595                 600                 605             


Asn Ser Leu Leu Ser Leu Pro Gln Glu Pro Tyr Ser Phe Ser Glu Pro 
    610                 615                 620                 


Ala Gln Gln Ala Met Arg Lys Ala Leu Thr Leu Arg Tyr Ala Leu Leu 
625                 630                 635                 640 


Pro His Leu Tyr Thr Leu Phe His Gln Ala His Val Ala Gly Glu Thr 
                645                 650                 655     


Val Ala Arg Pro Leu Phe Leu Glu Phe Pro Lys Asp Ser Ser Thr Trp 
            660                 665                 670         


Thr Val Asp His Gln Leu Leu Trp Gly Glu Ala Leu Leu Ile Thr Pro 
        675                 680                 685             


Val Leu Gln Ala Gly Lys Ala Glu Val Thr Gly Tyr Phe Pro Leu Gly 
    690                 695                 700                 


Thr Trp Tyr Asp Leu Gln Thr Val Pro Val Glu Ala Leu Gly Ser Leu 
705                 710                 715                 720 


Pro Pro Pro Pro Ala Ala Pro Arg Glu Pro Ala Ile His Ser Glu Gly 
                725                 730                 735     


Gln Trp Val Thr Leu Pro Ala Pro Leu Asp Thr Ile Asn Val His Leu 
            740                 745                 750         


Arg Ala Gly Tyr Ile Ile Pro Leu Gln Gly Pro Gly Leu Thr Thr Thr 
        755                 760                 765             


Glu Ser Arg Gln Gln Pro Met Ala Leu Ala Val Ala Leu Thr Lys Gly 
    770                 775                 780                 


Gly Glu Ala Arg Gly Glu Leu Phe Trp Asp Asp Gly Glu Ser Leu Glu 
785                 790                 795                 800 


Val Leu Glu Arg Gly Ala Tyr Thr Gln Val Ile Phe Leu Ala Arg Asn 
                805                 810                 815     


Asn Thr Ile Val Asn Glu Leu Val Arg Val Thr Ser Glu Gly Ala Gly 
            820                 825                 830         


Leu Gln Leu Gln Lys Val Thr Val Leu Gly Val Ala Thr Ala Pro Gln 
        835                 840                 845             


Gln Val Leu Ser Asn Gly Val Pro Val Ser Asn Phe Thr Tyr Ser Pro 
    850                 855                 860                 


Asp Thr Lys Val Leu Asp Ile Cys Val Ser Leu Leu Met Gly Glu Gln 
865                 870                 875                 880 


Phe Leu Val Ser Trp Cys 
                885     


<210>  51
<211>  883
<212>  PRT
<213>  Artificial

<220>
<223>  mature GAA amino acid sequence

<400>  51

Ala His Pro Gly Arg Pro Arg Ala Val Pro Thr Gln Cys Asp Val Pro 
1               5                   10                  15      


Pro Asn Ser Arg Phe Asp Cys Ala Pro Asp Lys Ala Ile Thr Gln Glu 
            20                  25                  30          


Gln Cys Glu Ala Arg Gly Cys Cys Tyr Ile Pro Ala Lys Gln Gly Leu 
        35                  40                  45              


Gln Gly Ala Gln Met Gly Gln Pro Trp Cys Phe Phe Pro Pro Ser Tyr 
    50                  55                  60                  


Pro Ser Tyr Lys Leu Glu Asn Leu Ser Ser Ser Glu Met Gly Tyr Thr 
65                  70                  75                  80  


Ala Thr Leu Thr Arg Thr Thr Pro Thr Phe Phe Pro Lys Asp Ile Leu 
                85                  90                  95      


Thr Leu Arg Leu Asp Val Met Met Glu Thr Glu Asn Arg Leu His Phe 
            100                 105                 110         


Thr Ile Lys Asp Pro Ala Asn Arg Arg Tyr Glu Val Pro Leu Glu Thr 
        115                 120                 125             


Pro His Val His Ser Arg Ala Pro Ser Pro Leu Tyr Ser Val Glu Phe 
    130                 135                 140                 


Ser Glu Glu Pro Phe Gly Val Ile Val Arg Arg Gln Leu Asp Gly Arg 
145                 150                 155                 160 


Val Leu Leu Asn Thr Thr Val Ala Pro Leu Phe Phe Ala Asp Gln Phe 
                165                 170                 175     


Leu Gln Leu Ser Thr Ser Leu Pro Ser Gln Tyr Ile Thr Gly Leu Ala 
            180                 185                 190         


Glu His Leu Ser Pro Leu Met Leu Ser Thr Ser Trp Thr Arg Ile Thr 
        195                 200                 205             


Leu Trp Asn Arg Asp Leu Ala Pro Thr Pro Gly Ala Asn Leu Tyr Gly 
    210                 215                 220                 


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


Val Phe Leu Leu Asn Ser Asn Ala Met Asp Val Val Leu Gln Pro Ser 
                245                 250                 255     


Pro Ala Leu Ser Trp Arg Ser Thr Gly Gly Ile Leu Asp Val Tyr Ile 
            260                 265                 270         


Phe Leu Gly Pro Glu Pro Lys Ser Val Val Gln Gln Tyr Leu Asp Val 
        275                 280                 285             


Val Gly Tyr Pro Phe Met Pro Pro Tyr Trp Gly Leu Gly Phe His Leu 
    290                 295                 300                 


Cys Arg Trp Gly Tyr Ser Ser Thr Ala Ile Thr Arg Gln Val Val Glu 
305                 310                 315                 320 


Asn Met Thr Arg Ala His Phe Pro Leu Asp Val Gln Trp Asn Asp Leu 
                325                 330                 335     


Asp Tyr Met Asp Ser Arg Arg Asp Phe Thr Phe Asn Lys Asp Gly Phe 
            340                 345                 350         


Arg Asp Phe Pro Ala Met Val Gln Glu Leu His Gln Gly Gly Arg Arg 
        355                 360                 365             


Tyr Met Met Ile Val Asp Pro Ala Ile Ser Ser Ser Gly Pro Ala Gly 
    370                 375                 380                 


Ser Tyr Arg Pro Tyr Asp Glu Gly Leu Arg Arg Gly Val Phe Ile Thr 
385                 390                 395                 400 


Asn Glu Thr Gly Gln Pro Leu Ile Gly Lys Val Trp Pro Gly Ser Thr 
                405                 410                 415     


Ala Phe Pro Asp Phe Thr Asn Pro Thr Ala Leu Ala Trp Trp Glu Asp 
            420                 425                 430         


Met Val Ala Glu Phe His Asp Gln Val Pro Phe Asp Gly Met Trp Ile 
        435                 440                 445             


Asp Met Asn Glu Pro Ser Asn Phe Ile Arg Gly Ser Glu Asp Gly Cys 
    450                 455                 460                 


Pro Asn Asn Glu Leu Glu Asn Pro Pro Tyr Val Pro Gly Val Val Gly 
465                 470                 475                 480 


Gly Thr Leu Gln Ala Ala Thr Ile Cys Ala Ser Ser His Gln Phe Leu 
                485                 490                 495     


Ser Thr His Tyr Asn Leu His Asn Leu Tyr Gly Leu Thr Glu Ala Ile 
            500                 505                 510         


Ala Ser His Arg Ala Leu Val Lys Ala Arg Gly Thr Arg Pro Phe Val 
        515                 520                 525             


Ile Ser Arg Ser Thr Phe Ala Gly His Gly Arg Tyr Ala Gly His Trp 
    530                 535                 540                 


Thr Gly Asp Val Trp Ser Ser Trp Glu Gln Leu Ala Ser Ser Val Pro 
545                 550                 555                 560 


Glu Ile Leu Gln Phe Asn Leu Leu Gly Val Pro Leu Val Gly Ala Asp 
                565                 570                 575     


Val Cys Gly Phe Leu Gly Asn Thr Ser Glu Glu Leu Cys Val Arg Trp 
            580                 585                 590         


Thr Gln Leu Gly Ala Phe Tyr Pro Phe Met Arg Asn His Asn Ser Leu 
        595                 600                 605             


Leu Ser Leu Pro Gln Glu Pro Tyr Ser Phe Ser Glu Pro Ala Gln Gln 
    610                 615                 620                 


Ala Met Arg Lys Ala Leu Thr Leu Arg Tyr Ala Leu Leu Pro His Leu 
625                 630                 635                 640 


Tyr Thr Leu Phe His Gln Ala His Val Ala Gly Glu Thr Val Ala Arg 
                645                 650                 655     


Pro Leu Phe Leu Glu Phe Pro Lys Asp Ser Ser Thr Trp Thr Val Asp 
            660                 665                 670         


His Gln Leu Leu Trp Gly Glu Ala Leu Leu Ile Thr Pro Val Leu Gln 
        675                 680                 685             


Ala Gly Lys Ala Glu Val Thr Gly Tyr Phe Pro Leu Gly Thr Trp Tyr 
    690                 695                 700                 


Asp Leu Gln Thr Val Pro Val Glu Ala Leu Gly Ser Leu Pro Pro Pro 
705                 710                 715                 720 


Pro Ala Ala Pro Arg Glu Pro Ala Ile His Ser Glu Gly Gln Trp Val 
                725                 730                 735     


Thr Leu Pro Ala Pro Leu Asp Thr Ile Asn Val His Leu Arg Ala Gly 
            740                 745                 750         


Tyr Ile Ile Pro Leu Gln Gly Pro Gly Leu Thr Thr Thr Glu Ser Arg 
        755                 760                 765             


Gln Gln Pro Met Ala Leu Ala Val Ala Leu Thr Lys Gly Gly Glu Ala 
    770                 775                 780                 


Arg Gly Glu Leu Phe Trp Asp Asp Gly Glu Ser Leu Glu Val Leu Glu 
785                 790                 795                 800 


Arg Gly Ala Tyr Thr Gln Val Ile Phe Leu Ala Arg Asn Asn Thr Ile 
                805                 810                 815     


Val Asn Glu Leu Val Arg Val Thr Ser Glu Gly Ala Gly Leu Gln Leu 
            820                 825                 830         


Gln Lys Val Thr Val Leu Gly Val Ala Thr Ala Pro Gln Gln Val Leu 
        835                 840                 845             


Ser Asn Gly Val Pro Val Ser Asn Phe Thr Tyr Ser Pro Asp Thr Lys 
    850                 855                 860                 


Val Leu Asp Ile Cys Val Ser Leu Leu Met Gly Glu Gln Phe Leu Val 
865                 870                 875                 880 


Ser Trp Cys 
            


<210>  52
<211>  937
<212>  PRT
<213>  Artificial

<220>
<223>  bovine GAA precursor protein

<400>  52

Met Met Arg Trp Pro Pro Cys Ser Arg Pro Leu Leu Gly Val Cys Thr 
1               5                   10                  15      


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


Val Val Pro Arg Glu Leu Arg Gly Phe Ser Gln Asp Glu Ile His Gln 
        35                  40                  45              


Ala Cys Gln Pro Gly Ala Ser Ser Pro Glu Cys Arg Gly Ser Pro Arg 
    50                  55                  60                  


Ala Ala Pro Thr Gln Cys Asp Leu Pro Pro Asn Ser Arg Phe Asp Cys 
65                  70                  75                  80  


Ala Pro Asp Lys Gly Ile Thr Pro Gln Gln Cys Glu Ala Arg Gly Cys 
                85                  90                  95      


Cys Tyr Met Pro Ala Glu Trp Pro Pro Asp Ala Gln Met Gly Gln Pro 
            100                 105                 110         


Trp Cys Phe Phe Pro Pro Ser Tyr Pro Ser Tyr Arg Leu Glu Asn Leu 
        115                 120                 125             


Thr Thr Thr Glu Thr Gly Tyr Thr Ala Thr Leu Thr Arg Ala Val Pro 
    130                 135                 140                 


Thr Phe Phe Pro Lys Asp Ile Met Thr Leu Arg Leu Asp Met Leu Met 
145                 150                 155                 160 


Glu Thr Glu Ser Arg Leu His Phe Thr Ile Lys Asp Pro Ala Asn Arg 
                165                 170                 175     


Arg Tyr Glu Val Pro Leu Glu Thr Pro Arg Val Tyr Ser Gln Ala Pro 
            180                 185                 190         


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


Val Arg Arg Lys Leu Asp Gly Arg Val Leu Leu Asn Thr Thr Val Ala 
    210                 215                 220                 


Pro Leu Phe Phe Ala Asp Gln Phe Leu Gln Leu Ser Thr Ser Leu Pro 
225                 230                 235                 240 


Ser Gln His Ile Thr Gly Leu Ala Glu His Leu Gly Ser Leu Met Leu 
                245                 250                 255     


Ser Thr Asn Trp Thr Lys Ile Thr Leu Trp Asn Arg Asp Ile Ala Pro 
            260                 265                 270         


Glu Pro Asn Val Asn Leu Tyr Gly Ser His Pro Phe Tyr Leu Val Leu 
        275                 280                 285             


Glu Asp Gly Gly Leu Ala His Gly Val Phe Leu Leu Asn Ser Asn Ala 
    290                 295                 300                 


Met Asp Val Val Leu Gln Pro Ser Pro Ala Leu Ser Trp Arg Ser Thr 
305                 310                 315                 320 


Gly Gly Ile Leu Asp Val Tyr Ile Phe Leu Gly Pro Glu Pro Lys Ser 
                325                 330                 335     


Val Val Gln Gln Tyr Leu Asp Val Val Gly Tyr Pro Phe Met Pro Pro 
            340                 345                 350         


Tyr Trp Gly Leu Gly Phe His Leu Cys Arg Trp Gly Tyr Ser Thr Ser 
        355                 360                 365             


Ala Ile Thr Arg Gln Val Val Glu Asn Met Thr Arg Ala Tyr Phe Pro 
    370                 375                 380                 


Leu Asp Val Gln Trp Asn Asp Leu Asp Tyr Met Asp Ala Arg Arg Asp 
385                 390                 395                 400 


Phe Thr Phe Asn Lys Asp His Phe Gly Asp Phe Pro Ala Met Val Gln 
                405                 410                 415     


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


Ile Ser Ser Ser Gly Pro Ala Gly Thr Tyr Arg Pro Tyr Asp Glu Gly 
        435                 440                 445             


Leu Arg Arg Gly Val Phe Ile Thr Asn Glu Thr Gly Gln Pro Leu Ile 
    450                 455                 460                 


Gly Gln Val Trp Pro Gly Leu Thr Ala Phe Pro Asp Phe Thr Asn Pro 
465                 470                 475                 480 


Glu Thr Leu Asp Trp Trp Gln Asp Met Val Thr Glu Phe His Ala Gln 
                485                 490                 495     


Val Pro Phe Asp Gly Met Trp Ile Asp Met Asn Glu Pro Ser Asn Phe 
            500                 505                 510         


Val Arg Gly Ser Val Asp Gly Cys Pro Asp Asn Ser Leu Glu Asn Pro 
        515                 520                 525             


Pro Tyr Leu Pro Gly Val Val Gly Gly Thr Leu Arg Ala Ala Thr Ile 
    530                 535                 540                 


Cys Ala Ser Ser His Gln Phe Leu Ser Thr His Tyr Asp Leu His Asn 
545                 550                 555                 560 


Leu Tyr Gly Leu Thr Glu Ala Leu Ala Ser His Arg Ala Leu Val Lys 
                565                 570                 575     


Ala Arg Gly Met Arg Pro Phe Val Ile Ser Arg Ser Thr Phe Ala Gly 
            580                 585                 590         


His Gly Arg Tyr Ser Gly His Trp Thr Gly Asp Val Trp Ser Asn Trp 
        595                 600                 605             


Glu Gln Leu Ser Tyr Ser Val Pro Glu Ile Leu Leu Phe Asn Leu Leu 
    610                 615                 620                 


Gly Val Pro Leu Val Gly Ala Asp Ile Cys Gly Phe Leu Gly Asn Thr 
625                 630                 635                 640 


Ser Glu Glu Leu Cys Val Arg Trp Thr Gln Leu Gly Ala Phe Tyr Pro 
                645                 650                 655     


Phe Met Arg Asn His Asn Ala Leu Asn Ser Gln Pro Gln Glu Pro Tyr 
            660                 665                 670         


Arg Phe Ser Glu Thr Ala Gln Gln Ala Met Arg Lys Ala Phe Thr Leu 
        675                 680                 685             


Arg Tyr Val Leu Leu Pro Tyr Leu Tyr Thr Leu Phe His Arg Ala His 
    690                 695                 700                 


Val Arg Gly Glu Thr Val Ala Arg Pro Leu Phe Leu Glu Phe Pro Glu 
705                 710                 715                 720 


Asp Pro Ser Thr Trp Thr Val Asp Arg Gln Leu Leu Trp Gly Glu Ala 
                725                 730                 735     


Leu Leu Ile Thr Pro Val Leu Glu Ala Glu Lys Val Glu Val Thr Gly 
            740                 745                 750         


Tyr Phe Pro Gln Gly Thr Trp Tyr Asp Leu Gln Thr Val Pro Met Glu 
        755                 760                 765             


Ala Phe Gly Ser Leu Pro Pro Pro Ala Pro Leu Thr Ser Val Ile His 
    770                 775                 780                 


Ser Lys Gly Gln Trp Val Thr Leu Ser Ala Pro Leu Asp Thr Ile Asn 
785                 790                 795                 800 


Val His Leu Arg Ala Gly His Ile Ile Pro Met Gln Gly Pro Ala Leu 
                805                 810                 815     


Thr Thr Thr Glu Ser Arg Lys Gln His Met Ala Leu Ala Val Ala Leu 
            820                 825                 830         


Thr Ala Ser Gly Glu Ala Gln Gly Glu Leu Phe Trp Asp Asp Gly Glu 
        835                 840                 845             


Ser Leu Gly Val Leu Asp Gly Gly Asp Tyr Thr Gln Leu Ile Phe Leu 
    850                 855                 860                 


Ala Lys Asn Asn Thr Phe Val Asn Lys Leu Val His Val Ser Ser Glu 
865                 870                 875                 880 


Gly Ala Ser Leu Gln Leu Arg Asn Val Thr Val Leu Gly Val Ala Thr 
                885                 890                 895     


Ala Pro Gln Gln Val Leu Cys Asn Ser Val Pro Val Ser Asn Phe Thr 
            900                 905                 910         


Phe Ser Pro Asp Thr Glu Thr Leu Ala Ile Pro Val Ser Leu Thr Met 
        915                 920                 925             


Gly Glu Gln Phe Val Ile Ser Trp Ser 
    930                 935         


<210>  53
<211>  28
<212>  PRT
<213>  Artificial

<220>
<223>  full linker region

<400>  53

His Ile Leu Leu His Asp Phe Leu Leu Val Pro Arg Glu Leu Ser Gly 
1               5                   10                  15      


Ser Ser Pro Val Leu Glu Glu Thr His Pro Ala His 
            20                  25              


