                         SEQUENCE LISTING

<110>  Charite - Universittsmedizin Berlin
 
<120>  Bone Morphogenetic Protein 2 (BMP2) variants with reduced BMP 
       antagonist sensitivity

<130>  P637109WO

<150>  EP09155049.1
<151>  2009-03-12

<160>  31    

<170>  PatentIn version 3.3

<210>  1
<211>  114
<212>  PRT
<213>  homo sapiens

<400>  1

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Asn His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Val Leu Lys Asn Tyr Gln Asp Met Val Val Glu Gly Cys Gly 
            100                 105                 110         


Cys Arg 
        


<210>  2
<211>  114
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  2

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Lys His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Thr Leu Lys Asn Tyr Gln Asp Met Val Val Glu Gly Cys Gly 
            100                 105                 110         


Cys Arg 
        


<210>  3
<211>  115
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  3

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Lys His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Val Leu Lys Tyr His Tyr Gln Asp Met Val Val Glu Gly Cys 
            100                 105                 110         


Gly Cys Arg 
        115 


<210>  4
<211>  114
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  4

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Thr His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Thr Leu Lys Asn Tyr Gln Asp Met Val Val Glu Gly Cys Gly 
            100                 105                 110         


Cys Arg 
        


<210>  5
<211>  115
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  5

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Thr His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Val Leu Lys Tyr His Tyr Gln Asp Met Val Val Glu Gly Cys 
            100                 105                 110         


Gly Cys Arg 
        115 


<210>  6
<211>  115
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  6

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Asn His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Thr Leu Lys Tyr His Tyr Gln Asp Met Val Val Glu Gly Cys 
            100                 105                 110         


Gly Cys Arg 
        115 


<210>  7
<211>  114
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  7

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Glu Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Thr His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Val Leu Lys Asn Tyr Gln Asp Met Val Val Glu Gly Cys Gly 
            100                 105                 110         


Cys Arg 
        


<210>  8
<211>  114
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  8

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Ser Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Lys Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Lys His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Val Leu Lys Asn Tyr Gln Asp Met Val Val Glu Gly Cys Gly 
            100                 105                 110         


Cys Arg 
        


<210>  9
<211>  115
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  9

Gln Ala Lys His Lys Gln Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg 
1               5                   10                  15      


His Pro Leu Tyr Val Asp Phe Glu Asp Val Gly Trp Asn Asp Trp Ile 
            20                  25                  30          


Val Ala Pro Pro Gly Tyr His Ala Phe Tyr Cys His Gly Glu Cys Pro 
        35                  40                  45              


Phe Pro Leu Ala Asp His Leu Asn Ser Thr Lys His Ala Ile Val Gln 
    50                  55                  60                  


Thr Leu Val Asn Ser Val Asn Ser Lys Ile Pro Lys Ala Cys Cys Val 
65                  70                  75                  80  


Pro Thr Glu Leu Ser Ala Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu 
                85                  90                  95      


Lys Val Val Leu Lys Tyr His Tyr Gln Asp Met Val Val Glu Gly Cys 
            100                 105                 110         


Gly Cys Arg 
        115 


<210>  10
<211>  282
<212>  PRT
<213>  homo sapiens

<400>  10

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg 
        275                 280         


<210>  11
<211>  396
<212>  PRT
<213>  homo sapiens

<400>  11

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn 
    370                 375                 380                 


Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395     


<210>  12
<211>  396
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  12

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Lys His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Thr Leu Lys Asn 
    370                 375                 380                 


Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395     


<210>  13
<211>  397
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  13

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Lys His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Tyr 
    370                 375                 380                 


His Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395         


<210>  14
<211>  396
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  14

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Thr His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Thr Leu Lys Asn 
    370                 375                 380                 


Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395     


<210>  15
<211>  397
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  15

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Thr His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Tyr 
    370                 375                 380                 


His Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395         


<210>  16
<211>  397
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  16

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Asn His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Thr Leu Lys Tyr 
    370                 375                 380                 


His Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395         


<210>  17
<211>  396
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  17

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Glu Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Thr His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn 
    370                 375                 380                 


Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395     


<210>  18
<211>  396
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  18

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Ser Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Lys Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Lys His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Asn 
    370                 375                 380                 


Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395     


<210>  19
<211>  397
<212>  PRT
<213>  artificial

<220>
<223>  isolated peptide of the invention

<400>  19

Met Val Ala Gly Thr Arg Cys Leu Leu Ala Leu Leu Leu Pro Gln Val 
1               5                   10                  15      


Leu Leu Gly Gly Ala Ala Gly Leu Val Pro Glu Leu Gly Arg Arg Lys 
            20                  25                  30          


Phe Ala Ala Ala Ser Ser Gly Arg Pro Ser Ser Gln Pro Ser Asp Glu 
        35                  40                  45              


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


Gln Arg Pro Thr Pro Ser Arg Asp Ala Val Val Pro Pro Tyr Met Leu 
65                  70                  75                  80  


Asp Leu Tyr Arg Arg His Ser Gly Gln Pro Gly Ser Pro Ala Pro Asp 
                85                  90                  95      


His Arg Leu Glu Arg Ala Ala Ser Arg Ala Asn Thr Val Arg Ser Phe 
            100                 105                 110         


His His Glu Glu Ser Leu Glu Glu Leu Pro Glu Thr Ser Gly Lys Thr 
        115                 120                 125             


Thr Arg Arg Phe Phe Phe Asn Leu Ser Ser Ile Pro Thr Glu Glu Phe 
    130                 135                 140                 


Ile Thr Ser Ala Glu Leu Gln Val Phe Arg Glu Gln Met Gln Asp Ala 
145                 150                 155                 160 


Leu Gly Asn Asn Ser Ser Phe His His Arg Ile Asn Ile Tyr Glu Ile 
                165                 170                 175     


Ile Lys Pro Ala Thr Ala Asn Ser Lys Phe Pro Val Thr Arg Leu Leu 
            180                 185                 190         


Asp Thr Arg Leu Val Asn Gln Asn Ala Ser Arg Trp Glu Ser Phe Asp 
        195                 200                 205             


Val Thr Pro Ala Val Met Arg Trp Thr Ala Gln Gly His Ala Asn His 
    210                 215                 220                 


Gly Phe Val Val Glu Val Ala His Leu Glu Glu Lys Gln Gly Val Ser 
225                 230                 235                 240 


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


Trp Ser Gln Ile Arg Pro Leu Leu Val Thr Phe Gly His Asp Gly Lys 
            260                 265                 270         


Gly His Pro Leu His Lys Arg Glu Lys Arg Gln Ala Lys His Lys Gln 
        275                 280                 285             


Arg Lys Arg Leu Lys Ser Ser Cys Lys Arg His Pro Leu Tyr Val Asp 
    290                 295                 300                 


Phe Glu Asp Val Gly Trp Asn Asp Trp Ile Val Ala Pro Pro Gly Tyr 
305                 310                 315                 320 


His Ala Phe Tyr Cys His Gly Glu Cys Pro Phe Pro Leu Ala Asp His 
                325                 330                 335     


Leu Asn Ser Thr Lys His Ala Ile Val Gln Thr Leu Val Asn Ser Val 
            340                 345                 350         


Asn Ser Lys Ile Pro Lys Ala Cys Cys Val Pro Thr Glu Leu Ser Ala 
        355                 360                 365             


Ile Ser Met Leu Tyr Leu Asp Glu Asn Glu Lys Val Val Leu Lys Tyr 
    370                 375                 380                 


His Tyr Gln Asp Met Val Val Glu Gly Cys Gly Cys Arg 
385                 390                 395         


<210>  20
<211>  57
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  20
ctgtaccttg acgagaatga aaaggttacg ttaaagaact atcaggacat ggttgtg        57


<210>  21
<211>  57
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  21
cacaaccatg tcctgatagt tctttaacgt aaccttttca ttctcgtcaa ggtacag        57


<210>  22
<211>  41
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  22
ccctttgtac gtggacttcg aggacgtggg gtggaatgac t                         41


<210>  23
<211>  41
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  23
agtcattcca ccccacgtcc tcgaagtcca cgtacaaagg g                         41


<210>  24
<211>  34
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  24
ctggattgtg gctcccaagg ggtatcacgc cttt                                 34


<210>  25
<211>  34
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  25
aaaggcgtga taccccttgg gagccacaat ccag                                 34


<210>  26
<211>  38
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  26
gctgatcatc tgaactccac taagcatgcc attgttca                             38


<210>  27
<211>  38
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  27
tgaacaatgg catgcttagt ggagttcaga tgatcagc                             38


<210>  28
<211>  33
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  28
gatcatctga actccactca tgccattgtt cag                                  33


<210>  29
<211>  36
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  29
gtctgaacaa tggcatgagt agtggagttc agatga                               36


<210>  30
<211>  50
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  30
gaatgaaaag gttgtattaa agtaccacta tcaggacatg gttgtggagg                50


<210>  31
<211>  50
<212>  DNA
<213>  artificial

<220>
<223>  primer

<400>  31
cctccacaac catgtcctga tagtggtact ttaatacaac cttttcattc                50


