                         SEQUENCE LISTING

<110>  Harding, Thomas
       Kavanaugh, Michael
 
<120>  USE OF FGFR1 EXTRA CELLULAR DOMAIN PROTEINS TO TREAT CANCERS 
       CHARACTERIZED BY LIGAND-DEPENDENT ACTIVATING MUTATIONS IN FGFR2

<130>  08940.6226-00000

<140>  US 61/261,291
<141>  2009-11-13

<160>  25    

<170>  PatentIn version 3.5

<210>  1
<211>  353
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD

<400>  1

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Pro Ala Val Met Thr Ser Pro Leu Tyr Leu 
            340                 345                 350         


Glu 
    


<210>  2
<211>  374
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD w/ signal peptide

<400>  2

Met Trp Ser Trp Lys Cys Leu Leu Phe Trp Ala Val Leu Val Thr Ala 
1               5                   10                  15      


Thr Leu Cys Thr Ala Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln 
            20                  25                  30          


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


Asp Leu Leu Gln Leu Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile 
    50                  55                  60                  


Asn Trp Leu Arg Asp Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg 
65                  70                  75                  80  


Ile Thr Gly Glu Glu Val Glu Val Gln Asp Ser Val Pro Ala Asp Ser 
                85                  90                  95      


Gly Leu Tyr Ala Cys Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr 
            100                 105                 110         


Tyr Phe Ser Val Asn Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp 
        115                 120                 125             


Asp Asp Asp Asp Asp Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr 
    130                 135                 140                 


Lys Pro Asn Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu 
145                 150                 155                 160 


Lys Lys Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys 
                165                 170                 175     


Pro Ser Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly 
            180                 185                 190         


Lys Glu Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Tyr 
        195                 200                 205             


Ala Thr Trp Ser Ile Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly 
    210                 215                 220                 


Asn Tyr Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr 
225                 230                 235                 240 


Tyr Gln Leu Asp Val Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln 
                245                 250                 255     


Ala Gly Leu Pro Ala Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu 
            260                 265                 270         


Phe Met Cys Lys Val Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu 
        275                 280                 285             


Lys His Ile Glu Val Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro 
    290                 295                 300                 


Tyr Val Gln Ile Leu Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu 
305                 310                 315                 320 


Met Glu Val Leu His Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu 
                325                 330                 335     


Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Leu Ser His His Ser Ala 
            340                 345                 350         


Trp Leu Thr Val Leu Glu Ala Leu Glu Glu Arg Pro Ala Val Met Thr 
        355                 360                 365             


Ser Pro Leu Tyr Leu Glu 
    370                 


<210>  3
<211>  349
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD delta4, (R1Mut1 ECD)

<400>  3

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Pro Ala Val Met Thr Ser Pro 
            340                 345                 


<210>  4
<211>  345
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD delta8; (R1Mut2 ECD)

<400>  4

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Pro Ala Val 
            340                 345 


<210>  5
<211>  344
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD delta9; (R1Mut3 ECD)

<400>  5

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Pro Ala 
            340                 


<210>  6
<211>  339
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD delta14; (R1Mut4 ECD)

<400>  6

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu 
            


<210>  7
<211>  334
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD delta19; (R1Mut5 ECD)

<400>  7

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr 
                325                 330                 


<210>  8
<211>  351
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD deltaP364 and A365; (R1Mut7 ECD)

<400>  8

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Val Met Thr Ser Pro Leu Tyr Leu Glu 
            340                 345                 350     


<210>  9
<211>  353
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD P364G; (R1Mut8 ECD)

<400>  9

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Gly Ala Val Met Thr Ser Pro Leu Tyr Leu 
            340                 345                 350         


Glu 
    


<210>  10
<211>  353
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD  P364M; (R1Mut9 ECD)

<400>  10

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Met Ala Val Met Thr Ser Pro Leu Tyr Leu 
            340                 345                 350         


Glu 
    


<210>  11
<211>  353
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD M367N; (R1Mut10 ECD)

<400>  11

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val 
        115                 120                 125             


Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala 
    130                 135                 140                 


Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr 
145                 150                 155                 160 


Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro 
                165                 170                 175     


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


Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys Ile 
        195                 200                 205             


Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln Leu Asp Val 
    210                 215                 220                 


Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala 
225                 230                 235                 240 


Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val 
                245                 250                 255     


Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile Glu Val 
            260                 265                 270         


Asn Gly Ser Lys Ile Gly Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu 
        275                 280                 285             


Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val Leu His 
    290                 295                 300                 


Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala 
305                 310                 315                 320 


Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr Val Leu 
                325                 330                 335     


Glu Ala Leu Glu Glu Arg Pro Ala Val Asn Thr Ser Pro Leu Tyr Leu 
            340                 345                 350         


Glu 
    


<210>  12
<211>  355
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 RM ECD

<400>  12

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg Ile Thr Gly Glu Glu 
    50                  55                  60                  


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


Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Asn 
                85                  90                  95      


Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp 
            100                 105                 110         


Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Arg Met 
        115                 120                 125             


Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu 
    130                 135                 140                 


His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser 
145                 150                 155                 160 


Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe 
                165                 170                 175     


Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Tyr Ala Thr Trp 
            180                 185                 190         


Ser Ile Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr 
        195                 200                 205             


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


Asp Val Val Glu Arg Ser Pro His Arg Pro Ile Leu Gln Ala Gly Leu 
225                 230                 235                 240 


Pro Ala Asn Lys Thr Val Ala Leu Gly Ser Asn Val Glu Phe Met Cys 
                245                 250                 255     


Lys Val Tyr Ser Asp Pro Gln Pro His Ile Gln Trp Leu Lys His Ile 
            260                 265                 270         


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


Ile Leu Lys Thr Ala Gly Val Asn Thr Thr Asp Lys Glu Met Glu Val 
    290                 295                 300                 


Leu His Leu Arg Asn Val Ser Phe Glu Asp Ala Gly Glu Tyr Thr Cys 
305                 310                 315                 320 


Leu Ala Gly Asn Ser Ile Gly Leu Ser His His Ser Ala Trp Leu Thr 
                325                 330                 335     


Val Leu Glu Ala Leu Glu Glu Arg Pro Ala Val Met Thr Ser Pro Leu 
            340                 345                 350         


Tyr Leu Glu 
        355 


<210>  13
<211>  21
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 signal peptide

<400>  13

Met Trp Ser Trp Lys Cys Leu Leu Phe Trp Ala Val Leu Val Thr Ala 
1               5                   10                  15      


Thr Leu Cys Thr Ala 
            20      


<210>  14
<211>  21
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR2 signal peptide

<400>  14

Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala 
            20      


<210>  15
<211>  22
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR3 signal peptide

<400>  15

Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile 
1               5                   10                  15      


Val Ala Gly Ala Ser Ser 
            20          


<210>  16
<211>  21
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR4 signal peptide

<400>  16

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


Pro Pro Val Leu Ser 
            20      


<210>  17
<211>  232
<212>  PRT
<213>  artificial sequence

<220>
<223>  Fc C237S

<400>  17

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
1               5                   10                  15      


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
            20                  25                  30          


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


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
    50                  55                  60                  


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                85                  90                  95      


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
            100                 105                 110         


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    130                 135                 140                 


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
145                 150                 155                 160 


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                165                 170                 175     


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


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
        195                 200                 205             


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
    210                 215                 220                 


Ser Leu Ser Leu Ser Pro Gly Lys 
225                 230         


<210>  18
<211>  228
<212>  PRT
<213>  artificial sequence

<220>
<223>  Fc

<400>  18

Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            180                 185                 190         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        195                 200                 205             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    210                 215                 220                 


Ser Pro Gly Lys 
225             


<210>  19
<211>  229
<212>  PRT
<213>  artificial sequence

<220>
<223>  Fc

<400>  19

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


Leu 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 Lys 
225                 


<210>  20
<211>  229
<212>  PRT
<213>  artificial sequence

<220>
<223>  Fc

<400>  20

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


Leu 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 Lys 
225                 


<210>  21
<211>  228
<212>  PRT
<213>  artificial sequence

<220>
<223>  Fc

<400>  21

Glu Arg Lys Ser Ser Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            180                 185                 190         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        195                 200                 205             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    210                 215                 220                 


Ser Pro Gly Lys 
225             


<210>  22
<211>  562
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR1 IIIc ECD delta14 + Fc; (R1Mut4)

<400>  22

Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln Pro Trp Gly Ala Pro 
1               5                   10                  15      


Val Glu Val Glu Ser Phe Leu Val His Pro Gly Asp Leu Leu Gln Leu 
            20                  25                  30          


Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile Asn Trp Leu Arg Asp 
        35                  40                  45              


Gly Val Gln Leu Ala Glu Ser Arg Thr Arg Ile Thr Gly Glu Glu Val 
    50                  55                  60                  


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


Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr Tyr Phe Ser Val Val Ser 
                85                  90                  95      


Asp Ala Leu Pro Ser Ser Glu Asp Asp Asp Asp Asp Asp Asp Ser Ser 
            100                 105                 110         


Ser Glu Glu Lys Glu Thr Asp Asn Thr Lys Pro Asn Pro Val Ala Pro 
        115                 120                 125             


Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His Ala Val Pro 
    130                 135                 140                 


Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly Thr Pro Asn 
145                 150                 155                 160 


Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys Pro Asp His 
                165                 170                 175     


Arg Ile Gly Gly Tyr Lys Val Arg Tyr Ala Thr Trp Ser Ile Ile Met 
            180                 185                 190         


Asp Ser Val Val Pro Ser Asp Lys Gly Tyr Thr Cys Ile Val Glu Asn 
        195                 200                 205             


Glu Tyr Gly Ser Ile His Thr Tyr Gln Leu Asp Val Val Glu Arg Ser 
    210                 215                 220                 


Pro His Arg Pro Ile Leu Gln Ala Gly Leu Pro Ala Lys Thr Val Ala 
225                 230                 235                 240 


Leu Gly Ser Asn Val Glu Phe Met Cys Lys Val Tyr Ser Asp Pro Gln 
                245                 250                 255     


Pro His Ile Gln Trp Leu Lys His Ile Glu Val Gly Ser Lys Ile Gly 
            260                 265                 270         


Pro Asp Asn Leu Pro Tyr Val Gln Ile Leu Lys Thr Ala Gly Val Thr 
        275                 280                 285             


Thr Asp Lys Glu Met Glu Val Leu His Leu Arg Val Ser Phe Glu Asp 
    290                 295                 300                 


Ala Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Leu Ser His 
305                 310                 315                 320 


His Ser Ala Trp Leu Thr Val Leu Glu Ala Leu Glu Pro Lys Ser Ser 
                325                 330                 335     


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
            340                 345                 350         


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
        355                 360                 365             


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
    370                 375                 380                 


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
385                 390                 395                 400 


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ser Thr Tyr Arg 
                405                 410                 415     


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
            420                 425                 430         


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
        435                 440                 445             


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
    450                 455                 460                 


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
465                 470                 475                 480 


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
                485                 490                 495     


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
            500                 505                 510         


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
        515                 520                 525             


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
    530                 535                 540                 


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
545                 550                 555                 560 


Gly Lys 
        


<210>  23
<211>  822
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR2 IIIb precursor (i.e. with signal peptide); GenBank Acc. No.
       NP_075259.2

<400>  23

Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 
            20                  25                  30          


Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 
        35                  40                  45              


Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 
    50                  55                  60                  


Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 
65                  70                  75                  80  


Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 
                85                  90                  95      


Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 
            100                 105                 110         


Val Asp Ser Glu Thr Trp Tyr Phe Met Val Asn Val Thr Asp Ala Ile 
        115                 120                 125             


Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 
    130                 135                 140                 


Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 
145                 150                 155                 160 


Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 
                165                 170                 175     


Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 
            180                 185                 190         


Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 
        195                 200                 205             


Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 
    210                 215                 220                 


Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 
225                 230                 235                 240 


Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg Pro 
                245                 250                 255     


Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 
            260                 265                 270         


Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 
        275                 280                 285             


Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 
    290                 295                 300                 


Gly Leu Pro Tyr Leu Lys Val Leu Lys His Ser Gly Ile Asn Ser Ser 
305                 310                 315                 320 


Asn Ala Glu Val Leu Ala Leu Phe Asn Val Thr Glu Ala Asp Ala Gly 
                325                 330                 335     


Glu Tyr Ile Cys Lys Val Ser Asn Tyr Ile Gly Gln Ala Asn Gln Ser 
            340                 345                 350         


Ala Trp Leu Thr Val Leu Pro Lys Gln Gln Ala Pro Gly Arg Glu Lys 
        355                 360                 365             


Glu Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile 
    370                 375                 380                 


Gly Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg 
385                 390                 395                 400 


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


His Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser 
            420                 425                 430         


Ala Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile 
        435                 440                 445             


Thr Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val 
    450                 455                 460                 


Ser Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp 
465                 470                 475                 480 


Lys Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val 
                485                 490                 495     


Val Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala 
            500                 505                 510         


Val Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp 
        515                 520                 525             


Leu Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys 
    530                 535                 540                 


His Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro 
545                 550                 555                 560 


Leu Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr 
                565                 570                 575     


Leu Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn 
            580                 585                 590         


Arg Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr 
        595                 600                 605             


Tyr Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile 
    610                 615                 620                 


His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val 
625                 630                 635                 640 


Met Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp 
                645                 650                 655     


Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala 
            660                 665                 670         


Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp 
        675                 680                 685             


Ser Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro 
    690                 695                 700                 


Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly 
705                 710                 715                 720 


His Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met 
                725                 730                 735     


Met Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys 
            740                 745                 750         


Gln Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu 
        755                 760                 765             


Glu Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr 
    770                 775                 780                 


Pro Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser 
785                 790                 795                 800 


Pro Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile 
                805                 810                 815     


Asn Gly Ser Val Lys Thr 
            820         


<210>  24
<211>  822
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR2 IIIb precursor S252W

<400>  24

Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 
            20                  25                  30          


Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 
        35                  40                  45              


Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 
    50                  55                  60                  


Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 
65                  70                  75                  80  


Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 
                85                  90                  95      


Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 
            100                 105                 110         


Val Asp Ser Glu Thr Trp Tyr Phe Met Val Asn Val Thr Asp Ala Ile 
        115                 120                 125             


Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 
    130                 135                 140                 


Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 
145                 150                 155                 160 


Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 
                165                 170                 175     


Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 
            180                 185                 190         


Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 
        195                 200                 205             


Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 
    210                 215                 220                 


Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 
225                 230                 235                 240 


Asn His Thr Tyr His Leu Asp Val Val Glu Arg Trp Pro His Arg Pro 
                245                 250                 255     


Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 
            260                 265                 270         


Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 
        275                 280                 285             


Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 
    290                 295                 300                 


Gly Leu Pro Tyr Leu Lys Val Leu Lys His Ser Gly Ile Asn Ser Ser 
305                 310                 315                 320 


Asn Ala Glu Val Leu Ala Leu Phe Asn Val Thr Glu Ala Asp Ala Gly 
                325                 330                 335     


Glu Tyr Ile Cys Lys Val Ser Asn Tyr Ile Gly Gln Ala Asn Gln Ser 
            340                 345                 350         


Ala Trp Leu Thr Val Leu Pro Lys Gln Gln Ala Pro Gly Arg Glu Lys 
        355                 360                 365             


Glu Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile 
    370                 375                 380                 


Gly Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg 
385                 390                 395                 400 


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


His Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser 
            420                 425                 430         


Ala Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile 
        435                 440                 445             


Thr Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val 
    450                 455                 460                 


Ser Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp 
465                 470                 475                 480 


Lys Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val 
                485                 490                 495     


Val Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala 
            500                 505                 510         


Val Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp 
        515                 520                 525             


Leu Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys 
    530                 535                 540                 


His Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro 
545                 550                 555                 560 


Leu Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr 
                565                 570                 575     


Leu Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn 
            580                 585                 590         


Arg Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr 
        595                 600                 605             


Tyr Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile 
    610                 615                 620                 


His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val 
625                 630                 635                 640 


Met Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp 
                645                 650                 655     


Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala 
            660                 665                 670         


Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp 
        675                 680                 685             


Ser Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro 
    690                 695                 700                 


Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly 
705                 710                 715                 720 


His Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met 
                725                 730                 735     


Met Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys 
            740                 745                 750         


Gln Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu 
        755                 760                 765             


Glu Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr 
    770                 775                 780                 


Pro Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser 
785                 790                 795                 800 


Pro Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile 
                805                 810                 815     


Asn Gly Ser Val Lys Thr 
            820         


<210>  25
<211>  822
<212>  PRT
<213>  artificial sequence

<220>
<223>  FGFR2 IIIb precursor P253R

<400>  25

Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 
            20                  25                  30          


Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 
        35                  40                  45              


Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 
    50                  55                  60                  


Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 
65                  70                  75                  80  


Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 
                85                  90                  95      


Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 
            100                 105                 110         


Val Asp Ser Glu Thr Trp Tyr Phe Met Val Asn Val Thr Asp Ala Ile 
        115                 120                 125             


Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 
    130                 135                 140                 


Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 
145                 150                 155                 160 


Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 
                165                 170                 175     


Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 
            180                 185                 190         


Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 
        195                 200                 205             


Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 
    210                 215                 220                 


Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 
225                 230                 235                 240 


Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Arg His Arg Pro 
                245                 250                 255     


Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 
            260                 265                 270         


Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 
        275                 280                 285             


Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 
    290                 295                 300                 


Gly Leu Pro Tyr Leu Lys Val Leu Lys His Ser Gly Ile Asn Ser Ser 
305                 310                 315                 320 


Asn Ala Glu Val Leu Ala Leu Phe Asn Val Thr Glu Ala Asp Ala Gly 
                325                 330                 335     


Glu Tyr Ile Cys Lys Val Ser Asn Tyr Ile Gly Gln Ala Asn Gln Ser 
            340                 345                 350         


Ala Trp Leu Thr Val Leu Pro Lys Gln Gln Ala Pro Gly Arg Glu Lys 
        355                 360                 365             


Glu Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile 
    370                 375                 380                 


Gly Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg 
385                 390                 395                 400 


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


His Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser 
            420                 425                 430         


Ala Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile 
        435                 440                 445             


Thr Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val 
    450                 455                 460                 


Ser Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp 
465                 470                 475                 480 


Lys Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val 
                485                 490                 495     


Val Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala 
            500                 505                 510         


Val Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp 
        515                 520                 525             


Leu Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys 
    530                 535                 540                 


His Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro 
545                 550                 555                 560 


Leu Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr 
                565                 570                 575     


Leu Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn 
            580                 585                 590         


Arg Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr 
        595                 600                 605             


Tyr Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile 
    610                 615                 620                 


His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val 
625                 630                 635                 640 


Met Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp 
                645                 650                 655     


Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala 
            660                 665                 670         


Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp 
        675                 680                 685             


Ser Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro 
    690                 695                 700                 


Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly 
705                 710                 715                 720 


His Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met 
                725                 730                 735     


Met Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys 
            740                 745                 750         


Gln Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu 
        755                 760                 765             


Glu Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr 
    770                 775                 780                 


Pro Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser 
785                 790                 795                 800 


Pro Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile 
                805                 810                 815     


Asn Gly Ser Val Lys Thr 
            820         


