﻿                         SEQUENCE LISTING

<110>  SUNSHINE LAKE PHARMA CO., LTD.

<120>  FGF21 variant, fusion protein and application thereof

<130>  2018

<141>  2018-12-25

<160>  37

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  181
<212>  PRT
<213>  Homo sapiens

<400>  1
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      
Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 
Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 
Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
                165                 170                 175     
Pro Ser Tyr Ala Ser 
            180     

<210>  2
<211>  181
<212>  PRT
<213>  Artificial sequence

<220>
<223>  FGF21 variant


<220>
<221>  UNSURE
<222>  (98)..(98)
<223>  Xaa at position 98 is Leu, Arg, Asp, Glu or Lys


<220>
<221>  UNSURE
<222>  (113)..(114)
<223>  Xaa at position 113 is Gly or Arg; Xaa at position 114 is Leu or Gln


<220>
<221>  UNSURE
<222>  (135)..(135)
<223>  Xaa at position 135 is Arg or Cys


<220>
<221>  UNSURE
<222>  (167)..(167)
<223>  Xaa at position 167 is Ser, Cys, Arg or His


<220>
<221>  UNSURE
<222>  (171)..(171)
<223>  Xaa at position 171 is Pro, Cys, Gly or Ala


<220>
<221>  UNSURE
<222>  (175)..(175)
<223>  Xaa at position 175 is Arg, His, Pro or Leu

<400>  2
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      
Glu Xaa Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         
Xaa Xaa Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             
Ala Pro Arg Gly Pro Ala Xaa Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 
Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 
Gly Ser Ser Asp Pro Leu Xaa Met Val Gly Xaa Ser Gln Gly Xaa Ser 
                165                 170                 175     
Pro Ser Tyr Ala Ser 
            180     

<210>  3
<211>  181
<212>  PRT
<213>  Artificial sequence

<220>
<223>  FGF21 98R171A167H175L


<400>  3
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      
Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 
Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 
Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly Leu Ser 
                165                 170                 175     
Pro Ser Tyr Ala Ser 
            180     

<210>  4
<211>  181
<212>  PRT
<213>  Artificial sequence

<220>
<223>  FGF2198R171G167H175L


<400>  4
His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      
Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          
Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              
Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  
Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  
Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      
Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         
Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             
Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 
Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 
Gly Ser Ser Asp Pro Leu His Met Val Gly Gly Ser Gln Gly Leu Ser 
                165                 170                 175     
Pro Ser Tyr Ala Ser 
            180     

<210>  5
<211>  228
<212>  PRT
<213>  Artificial sequence

<220>
<223>  fc lily


<400>  5
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly 
225             

<210>  6
<211>  228
<212>  PRT
<213> Artificial sequence

<220>
<223>  IgG4 Fc hec


<400>  6
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly 
225             

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

<220>
<223>  linker


<400>  7
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  

<210>  8
<211>  16
<212>  PRT
<213>  Artificial sequence

<220>
<223>  linker a


<400>  8
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala 
1               5                   10                  15      

<210>  9
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，167H，171A


<400>  9
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln 
                405                 410                 415     
Gly Arg Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  10
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171A，167H，175L


<400>  10
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln 
                405                 410                 415     
Gly Leu Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  11
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171G，167H,175L


<400>  11
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu His Met Val Gly Gly Ser Gln 
                405                 410                 415     
Gly Leu Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  12
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171A，167H，175P


<400>  12
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln 
                405                 410                 415     
Gly Pro Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  13
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171A，167H，175H


<400>  13
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln 
                405                 410                 415     
Gly His Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  14
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171A，167H,175P，113R，114Q，135C


<400>  14
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Arg Gln Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Cys Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln 
                405                 410                 415     
Gly Pro Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  15
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogues


<400>  15
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly 
            20                  25                  30      

<210>  16
<211>  470
<212>  PRT
<213>  Artificial sequence

<220>
<223>  D 98R，171A，167H


<400>  16
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly 
            20                  25                  30          
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ser 
        35                  40                  45              
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
    50                  55                  60                  
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
65                  70                  75                  80  
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln 
                85                  90                  95      
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            100                 105                 110         
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr 
        115                 120                 125             
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
    130                 135                 140                 
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile 
145                 150                 155                 160 
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                165                 170                 175     
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser 
            180                 185                 190         
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        195                 200                 205             
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    210                 215                 220                 
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
225                 230                 235                 240 
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met 
                245                 250                 255     
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            260                 265                 270         
Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        275                 280                 285             
Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln 
    290                 295                 300                 
Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala 
305                 310                 315                 320 
His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln 
                325                 330                 335     
Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile 
            340                 345                 350         
Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp 
        355                 360                 365             
Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe 
    370                 375                 380                 
Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala 
385                 390                 395                 400 
His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp 
                405                 410                 415     
Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro 
            420                 425                 430         
Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp 
        435                 440                 445             
Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly Arg 
    450                 455                 460                 
Ser Pro Ser Tyr Ala Ser 
465                 470 

<210>  17
<211>  470
<212>  PRT
<213>  Artificial sequence

<220>
<223>  D 98R，171A，167H、175L


<400>  17
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly 
            20                  25                  30          
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ser 
        35                  40                  45              
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
    50                  55                  60                  
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
65                  70                  75                  80  
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln 
                85                  90                  95      
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            100                 105                 110         
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr 
        115                 120                 125             
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
    130                 135                 140                 
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile 
145                 150                 155                 160 
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                165                 170                 175     
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser 
            180                 185                 190         
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        195                 200                 205             
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    210                 215                 220                 
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
225                 230                 235                 240 
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met 
                245                 250                 255     
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            260                 265                 270         
Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        275                 280                 285             
Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln 
    290                 295                 300                 
Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala 
305                 310                 315                 320 
His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln 
                325                 330                 335     
Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile 
            340                 345                 350         
Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp 
        355                 360                 365             
Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe 
    370                 375                 380                 
Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala 
385                 390                 395                 400 
His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp 
                405                 410                 415     
Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro 
            420                 425                 430         
Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp 
        435                 440                 445             
Val Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly Leu 
    450                 455                 460                 
Ser Pro Ser Tyr Ala Ser 
465                 470 

<210>  18
<211>  470
<212>  PRT
<213>  Artificial sequence

<220>
<223>  D 98R，171G，167H、175L


<400>  18
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Gly Gly Gly 
            20                  25                  30          
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ser 
        35                  40                  45              
Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
    50                  55                  60                  
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
65                  70                  75                  80  
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln 
                85                  90                  95      
Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            100                 105                 110         
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr 
        115                 120                 125             
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
    130                 135                 140                 
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile 
145                 150                 155                 160 
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                165                 170                 175     
Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser 
            180                 185                 190         
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        195                 200                 205             
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    210                 215                 220                 
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
225                 230                 235                 240 
Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met 
                245                 250                 255     
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            260                 265                 270         
Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        275                 280                 285             
Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln 
    290                 295                 300                 
Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala 
305                 310                 315                 320 
His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln 
                325                 330                 335     
Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile 
            340                 345                 350         
Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp 
        355                 360                 365             
Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe 
    370                 375                 380                 
Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala 
385                 390                 395                 400 
His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp 
                405                 410                 415     
Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro 
            420                 425                 430         
Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp 
        435                 440                 445             
Val Gly Ser Ser Asp Pro Leu His Met Val Gly Gly Ser Gln Gly Leu 
    450                 455                 460                 
Ser Pro Ser Tyr Ala Ser 
465                 470 

<210>  19
<211>  1272
<212>  DNA
<213>  Artificial sequence

<220>
<223>  DNA S 98R，171A，167H


<400>  19
gagagcaagt acggcccccc ctgtcctcct tgccccgccc ctgaggccgc cggcggccct        60
agcgtgtttc tgtttccccc caagcctaaa gacaccctga tgatctccag gacccctgag       120
gtgacctgtg tggtggtgga cgtgagccag gaggaccccg aggtgcagtt caactggtac       180
gtggatggcg tggaagtgca caacgccaag accaagccca gggaggagca attcaacagc       240
acctacaggg tggtgagcgt cctcaccgtc ctgcatcagg actggctgaa cggcaaggag       300
tacaagtgca aagtgtccaa caagggcctg ccttcctcca tcgagaagac catctccaag       360
gctaagggcc agcccaggga accccaagtg tacaccctcc ccccctccca ggaggagatg       420
accaaaaacc aagtctccct gacctgcctg gtgaagggct tctacccctc cgatattgcc       480
gtcgagtggg agagcaacgg ccagcccgag aacaactata agaccacccc ccccgtgctg       540
gattccgacg gttctttttt cctgtatagc aagctgaccg tggacaagtc caggtggcag       600
gagggcaacg tgttctcctg cagcgtgatg cacgaggccc tccacaacca ctacacccag       660
aaatccctgt ccctgtccct cggcggcgga ggcggctccg gcggcggcgg cagcggaggc       720
ggaggaagcc atcccattcc cgactccagc cccctgctgc agtttggcgg ccaagtgagg       780
cagagatacc tgtacaccga cgatgcccaa cagacagagg ctcacctgga aatcagggag       840
gacggcaccg tgggcggagc tgctgatcag agccccgagt ccctcctcca gctgaaggcc       900
ctgaagcccg gagtgatcca gatcctgggc gtgaagacat ccaggttcct gtgccagaga       960
cccgatggcg ccctgtacgg aagcctgcac ttcgaccccg aggcttgctc cttcagggag      1020
aggctgctgg aggacggcta caacgtgtac cagtccgagg ctcacggact ccctctgcac      1080
ctgcctggca acaagagccc tcacagagac cccgccccta gaggccctgc taggtttctg      1140
cccctgcctg gcctgcctcc tgctctgccc gagccccctg gtattttagc tcctcagcct      1200
cccgatgtgg gaagcagcga ccccctgcac atggtgggag ctagccaggg caggagccct      1260
agctacgcca gc                                                          1314

<210>  20
<211>  1272
<212>  DNA
<213>  Artificial sequence

<220>
<223>  SDNA 98R171A167H175L


<400>  20
gagagcaagt acggcccccc ctgtcctcct tgccccgccc ctgaggccgc cggcggccct        60
agcgtgtttc tgtttccccc caagcctaaa gacaccctga tgatctccag gacccctgag       120
gtgacctgtg tggtggtgga cgtgagccag gaggaccccg aggtgcagtt caactggtac       180
gtggatggcg tggaagtgca caacgccaag accaagccca gggaggagca attcaacagc       240
acctacaggg tggtgagcgt cctcaccgtc ctgcatcagg actggctgaa cggcaaggag       300
tacaagtgca aagtgtccaa caagggcctg ccttcctcca tcgagaagac catctccaag       360
gctaagggcc agcccaggga accccaagtg tacaccctcc ccccctccca ggaggagatg       420
accaaaaacc aagtctccct gacctgcctg gtgaagggct tctacccctc cgatattgcc       480
gtcgagtggg agagcaacgg ccagcccgag aacaactata agaccacccc ccccgtgctg       540
gattccgacg gttctttttt cctgtatagc aagctgaccg tggacaagtc caggtggcag       600
gagggcaacg tgttctcctg cagcgtgatg cacgaggccc tccacaacca ctacacccag       660
aaatccctgt ccctgtccct cggcggcgga ggcggctccg gcggcggcgg cagcggaggc       720
ggaggaagcc atcccattcc cgactccagc cccctgctgc agtttggcgg ccaagtgagg       780
cagagatacc tgtacaccga cgatgcccaa cagacagagg ctcacctgga aatcagggag       840
gacggcaccg tgggcggagc tgctgatcag agccccgagt ccctcctcca gctgaaggcc       900
ctgaagcccg gagtgatcca gatcctgggc gtgaagacat ccaggttcct gtgccagaga       960
cccgatggcg ccctgtacgg aagcctgcac ttcgaccccg aggcttgctc cttcagggag      1020
aggctgctgg aggacggcta caacgtgtac cagtccgagg ctcacggact ccctctgcac      1080
ctgcctggca acaagagccc tcacagagac cccgccccta gaggccctgc taggtttctg      1140
cccctgcctg gcctgcctcc tgctctgccc gagccccctg gtattttagc tcctcagcct      1200
cccgatgtgg gaagcagcga ccccctgcac atggtgggag ctagccaggg cctgagccct      1260
agctacgcca gc                                                          1314

<210>  21
<211>  1272
<212>  DNA
<213>  Artificial sequence

<220>
<223>  S DNA 98R，171A，167H，175P


<400>  21
gagagcaagt acggcccccc ctgtcctcct tgccccgccc ctgaggccgc cggcggccct        60
agcgtgtttc tgtttccccc caagcctaaa gacaccctga tgatctccag gacccctgag       120
gtgacctgtg tggtggtgga cgtgagccag gaggaccccg aggtgcagtt caactggtac       180
gtggatggcg tggaagtgca caacgccaag accaagccca gggaggagca attcaacagc       240
acctacaggg tggtgagcgt cctcaccgtc ctgcatcagg actggctgaa cggcaaggag       300
tacaagtgca aagtgtccaa caagggcctg ccttcctcca tcgagaagac catctccaag       360
gctaagggcc agcccaggga accccaagtg tacaccctcc ccccctccca ggaggagatg       420
accaaaaacc aagtctccct gacctgcctg gtgaagggct tctacccctc cgatattgcc       480
gtcgagtggg agagcaacgg ccagcccgag aacaactata agaccacccc ccccgtgctg       540
gattccgacg gttctttttt cctgtatagc aagctgaccg tggacaagtc caggtggcag       600
gagggcaacg tgttctcctg cagcgtgatg cacgaggccc tccacaacca ctacacccag       660
aaatccctgt ccctgtccct cggcggcgga ggcggctccg gcggcggcgg cagcggaggc       720
ggaggaagcc atcccattcc cgactccagc cccctgctgc agtttggcgg ccaagtgagg       780
cagagatacc tgtacaccga cgatgcccaa cagacagagg ctcacctgga aatcagggag       840
gacggcaccg tgggcggagc tgctgatcag agccccgagt ccctcctcca gctgaaggcc       900
ctgaagcccg gagtgatcca gatcctgggc gtgaagacat ccaggttcct gtgccagaga       960
cccgatggcg ccctgtacgg aagcctgcac ttcgaccccg aggcttgctc cttcagggag      1020
aggctgctgg aggacggcta caacgtgtac cagtccgagg ctcacggact ccctctgcac      1080
ctgcctggca acaagagccc tcacagagac cccgccccta gaggccctgc taggtttctg      1140
cccctgcctg gcctgcctcc tgctctgccc gagccccctg gtattttagc tcctcagcct      1200
cccgatgtgg gaagcagcga ccccctgcac atggtgggag ctagccaggg ccctagccct      1260
agctacgcca gc                                                          1314

<210>  22
<211>  1272
<212>  DNA
<213>  Artificial sequence

<220>
<223>  SDNA 98R，171A，167H，175H


<400>  22
gagagcaagt acggcccccc ctgtcctcct tgccccgccc ctgaggccgc cggcggccct        60
agcgtgtttc tgtttccccc caagcctaaa gacaccctga tgatctccag gacccctgag       120
gtgacctgtg tggtggtgga cgtgagccag gaggaccccg aggtgcagtt caactggtac       180
gtggatggcg tggaagtgca caacgccaag accaagccca gggaggagca attcaacagc       240
acctacaggg tggtgagcgt cctcaccgtc ctgcatcagg actggctgaa cggcaaggag       300
tacaagtgca aagtgtccaa caagggcctg ccttcctcca tcgagaagac catctccaag       360
gctaagggcc agcccaggga accccaagtg tacaccctcc ccccctccca ggaggagatg       420
accaaaaacc aagtctccct gacctgcctg gtgaagggct tctacccctc cgatattgcc       480
gtcgagtggg agagcaacgg ccagcccgag aacaactata agaccacccc ccccgtgctg       540
gattccgacg gttctttttt cctgtatagc aagctgaccg tggacaagtc caggtggcag       600
gagggcaacg tgttctcctg cagcgtgatg cacgaggccc tccacaacca ctacacccag       660
aaatccctgt ccctgtccct cggcggcgga ggcggctccg gcggcggcgg cagcggaggc       720
ggaggaagcc atcccattcc cgactccagc cccctgctgc agtttggcgg ccaagtgagg       780
cagagatacc tgtacaccga cgatgcccaa cagacagagg ctcacctgga aatcagggag       840
gacggcaccg tgggcggagc tgctgatcag agccccgagt ccctcctcca gctgaaggcc       900
ctgaagcccg gagtgatcca gatcctgggc gtgaagacat ccaggttcct gtgccagaga       960
cccgatggcg ccctgtacgg aagcctgcac ttcgaccccg aggcttgctc cttcagggag      1020
aggctgctgg aggacggcta caacgtgtac cagtccgagg ctcacggact ccctctgcac      1080
ctgcctggca acaagagccc tcacagagac cccgccccta gaggccctgc taggtttctg      1140
cccctgcctg gcctgcctcc tgctctgccc gagccccctg gtattttagc tcctcagcct      1200
cccgatgtgg gaagcagcga ccccctgcac atggtgggag ctagccaggg ccacagccct      1260
agctacgcca gc                                                          1314

<210>  23
<211>  1272
<212>  DNA
<213>  Artificial sequence

<220>
<223>  SDNA 98R，171A，167H，175P，113R，114Q，135C


<400>  23
gagagcaagt atggcccccc ttgtcctccc tgtcccgctc ctgaggccgc cggcggcccc        60
agcgtgtttc tgtttccccc caagcccaaa gacacactga tgatcagcag gacacccgaa       120
gtgacctgcg tggtcgtgga cgtgtcccag gaagaccccg aggtgcagtt taactggtac       180
gtcgacggag tcgaggtgca caacgccaag accaagccca gagaggagca gttcaacagc       240
acctacagag tggtgagcgt gctgaccgtg ctgcatcagg actggctgaa cggcaaggag       300
tacaagtgca aggtcagcaa caagggcctg cctagcagca tcgagaagac catctccaag       360
gccaagggcc aacccaggga accccaagtg tacaccctgc ctcccagcca ggaggagatg       420
accaagaacc aggtgtccct gacctgcctc gtcaagggct tttacccttc cgacatcgcc       480
gtggagtggg aatccaacgg ccagcccgag aataactaca aaaccacccc ccccgtgctc       540
gatagcgatg gctccttctt cctctacagc aagctgacag tcgataagtc caggtggcag       600
gagggaaacg tcttctcctg cagcgtgatg cacgaggctc tccacaacca ctacacccag       660
aagtccctga gcctgagcct gggcggcggc ggcggcagcg gcggcggagg cagcggcggc       720
ggcggaagcc atcccatccc tgatagcagc cctctgctcc agttcggcgg ccaagtgagg       780
cagagatacc tgtacaccga cgatgcccag cagacagaag cccacctgga gatcagagag       840
gacggaacag tgggcggagc tgccgaccag tcccccgaat ccctgctgca gctgaaggcc       900
ctgaagcccg gagtgatcca gatcctgggc gtcaagacct ccaggttcct gtgccagagg       960
cccgatggcg ctctgtatgg cagcctgcac tttgaccccg aggcctgttc cttcagggag      1020
agactcctgg aggatggcta taacgtctac cagtccgaag cccacagaca gcccctgcac      1080
ctgcccggca acaaatcccc tcacagggat cctgctccca gaggccctgc ttgcttcctg      1140
cctctccctg gactgcctcc tgccctcccc gaacctcctg gcattctggc ccctcagcct      1200
cctgatgtgg gcagcagcga ccctctgcac atggtgggag ccagccaagg acccagcccc      1260
tcctacgcca gc                                                          1314

<210>  24
<211>  1410
<212>  DNA
<213>  Artificial sequence

<220>
<223>  DDNA 98R，171A，167H


<400>  24
catggcgagg gcacctttac ctccgacgtg tcctcctacc tggaagaaca ggccgccaaa        60
gagtttatcg cctggctcgt gaagggcggt ggtggcggcg gaggatctgg cggaggtgga       120
agcggaggcg gtggatctga gagcaagtac ggccccccct gtcctccttg ccccgcccct       180
gaggccgccg gcggccctag cgtgtttctg tttcccccca agcctaaaga caccctgatg       240
atctccagga cccctgaggt gacctgtgtg gtggtggacg tgagccagga ggaccccgag       300
gtgcagttca actggtacgt ggatggcgtg gaagtgcaca acgccaagac caagcccagg       360
gaggagcaat tcaacagcac ctacagggtg gtgagcgtcc tcaccgtcct gcatcaggac       420
tggctgaacg gcaaggagta caagtgcaaa gtgtccaaca agggcctgcc ttcctccatc       480
gagaagacca tctccaaggc taagggccag cccagggaac cccaagtgta caccctcccc       540
ccctcccagg aggagatgac caaaaaccaa gtctccctga cctgcctggt gaagggcttc       600
tacccctccg atattgccgt cgagtgggag agcaacggcc agcccgagaa caactataag       660
accacccccc ccgtgctgga ttccgacggt tcttttttcc tgtatagcaa gctgaccgtg       720
gacaagtcca ggtggcagga gggcaacgtg ttctcctgca gcgtgatgca cgaggccctc       780
cacaaccact acacccagaa atccctgtcc ctgtccctcg gcggcggagg cggctccggc       840
ggcggcggca gcggaggcgg aggaagccat cccattcccg actccagccc cctgctgcag       900
tttggcggcc aagtgaggca gagatacctg tacaccgacg atgcccaaca gacagaggct       960
cacctggaaa tcagggagga cggcaccgtg ggcggagctg ctgatcagag ccccgagtcc      1020
ctcctccagc tgaaggccct gaagcccgga gtgatccaga tcctgggcgt gaagacatcc      1080
aggttcctgt gccagagacc cgatggcgcc ctgtacggaa gcctgcactt cgaccccgag      1140
gcttgctcct tcagggagag gctgctggag gacggctaca acgtgtacca gtccgaggct      1200
cacggactcc ctctgcacct gcctggcaac aagagccctc acagagaccc cgcccctaga      1260
ggccctgcta ggtttctgcc cctgcctggc ctgcctcctg ctctgcccga gccccctggt      1320
attttagctc ctcagcctcc cgatgtggga agcagcgacc ccctgcacat ggtgggagct      1380
agccagggca ggagccctag ctacgccagc                                       1456

<210>  25
<211>  1410
<212>  DNA
<213>  Artificial sequence

<220>
<223>  DDNA 98R，171A，167H，175L


<400>  25
catggcgagg gcacctttac ctccgacgtg tcctcctacc tggaagaaca ggccgccaaa        60
gagtttatcg cctggctcgt gaagggcggt ggtggcggcg gaggatctgg cggaggtgga       120
agcggaggcg gtggatctga gagcaagtac ggccccccct gtcctccttg ccccgcccct       180
gaggccgccg gcggccctag cgtgtttctg tttcccccca agcctaaaga caccctgatg       240
atctccagga cccctgaggt gacctgtgtg gtggtggacg tgagccagga ggaccccgag       300
gtgcagttca actggtacgt ggatggcgtg gaagtgcaca acgccaagac caagcccagg       360
gaggagcaat tcaacagcac ctacagggtg gtgagcgtcc tcaccgtcct gcatcaggac       420
tggctgaacg gcaaggagta caagtgcaaa gtgtccaaca agggcctgcc ttcctccatc       480
gagaagacca tctccaaggc taagggccag cccagggaac cccaagtgta caccctcccc       540
ccctcccagg aggagatgac caaaaaccaa gtctccctga cctgcctggt gaagggcttc       600
tacccctccg atattgccgt cgagtgggag agcaacggcc agcccgagaa caactataag       660
accacccccc ccgtgctgga ttccgacggt tcttttttcc tgtatagcaa gctgaccgtg       720
gacaagtcca ggtggcagga gggcaacgtg ttctcctgca gcgtgatgca cgaggccctc       780
cacaaccact acacccagaa atccctgtcc ctgtccctcg gcggcggagg cggctccggc       840
ggcggcggca gcggaggcgg aggaagccat cccattcccg actccagccc cctgctgcag       900
tttggcggcc aagtgaggca gagatacctg tacaccgacg atgcccaaca gacagaggct       960
cacctggaaa tcagggagga cggcaccgtg ggcggagctg ctgatcagag ccccgagtcc      1020
ctcctccagc tgaaggccct gaagcccgga gtgatccaga tcctgggcgt gaagacatcc      1080
aggttcctgt gccagagacc cgatggcgcc ctgtacggaa gcctgcactt cgaccccgag      1140
gcttgctcct tcagggagag gctgctggag gacggctaca acgtgtacca gtccgaggct      1200
cacggactcc ctctgcacct gcctggcaac aagagccctc acagagaccc cgcccctaga      1260
ggccctgcta ggtttctgcc cctgcctggc ctgcctcctg ctctgcccga gccccctggt      1320
attttagctc ctcagcctcc cgatgtggga agcagcgacc ccctgcacat ggtgggagct      1380
agccagggcc tgagccctag ctacgccagc                                       1456

<210>  26
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171A


<400>  26
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Ala Ser Gln 
                405                 410                 415     
Gly Arg Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  27
<211>  424
<212>  PRT
<213>  Artificial sequence

<220>
<223>  S 98R，171G


<400>  27
Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      
Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            20                  25                  30          
Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              
Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  
Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  
Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      
Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         
Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             
Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 
Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 
Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     
Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190         
Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser 
        195                 200                 205             
Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    210                 215                 220                 
Leu Ser Leu Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
225                 230                 235                 240 
Gly Gly Ser His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly 
                245                 250                 255     
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr 
            260                 265                 270         
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala 
        275                 280                 285             
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly 
    290                 295                 300                 
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg 
305                 310                 315                 320 
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys 
                325                 330                 335     
Ser Phe Arg Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser 
            340                 345                 350         
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His 
        355                 360                 365             
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly 
    370                 375                 380                 
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro 
385                 390                 395                 400 
Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Gly Ser Gln 
                405                 410                 415     
Gly Arg Ser Pro Ser Tyr Ala Ser 
            420                 

<210>  28
<211>  31
<212>  PRT
<213>  Artificial sequence

<220>
<223>  GLP-1 analogues


<400>  28
His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Glu 
1               5                   10                  15      
Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly 
            20                  25                  30      

<210>  29
<211>  37
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer AUZ-F


<400>  29
cccaagcttg ccgccaccat gaccagactg accgtgc                                 37

<210>  30
<211>  35
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer lfc1-R



<400>  30
gccgtacttg ctctcagatc caccgcctcc gcttc                                   35

<210>  31
<211>  34
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer lfc1-F


<400>  31
gcggaggcgg tggatctgag agcaagtacg gccc                                    34

<210>  32
<211>  33
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Primer fgf21-R


<400>  32
ccggaattct catcagctgg cgtagctagg gct                                     33

<210>  33
<211>  192
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Control fusion protein SPC

<400>  33

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala 
1               5                   10                  15      


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


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        35                  40                  45              


Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val 
    50                  55                  60                  


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser 
65                  70                  75                  80  


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                85                  90                  95      


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser 
            100                 105                 110         


Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        115                 120                 125             


Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln 
    130                 135                 140                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
145                 150                 155                 160 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                165                 170                 175     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            180                 185                 190   


<210>  34
<211>  181
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Sequence of FGF21 variants in S1

<400>  34

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


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


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


Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  


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


Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  35
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Sequence of FGF21 variants in S4

<400>  35

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


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


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


Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  


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


Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly Pro Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  36
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Sequence of FGF21 variants in S5

<400>  36

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


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


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


Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  


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


Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly His Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  37
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Sequence of FGF21 variants in S6

<400>  37

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


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


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


Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
65                  70                  75                  80  


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


Glu Arg Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gln Gln Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Cys Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu His Met Val Gly Ala Ser Gln Gly Pro Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     



      





      

