                         SEQUENCE LISTING

<110>  ETH Zrich et al. 
 
<120>  Means and methods for determining clostridial neurotoxins

<130>  T2163 PCT

<150>  EP 11 00 5915.1
<151>  2011-07-19

<160>  21    

<170>  PatentIn version 3.5

<210>  1
<211>  376
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


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


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


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


Leu Leu Thr Arg Asn Val Glu Arg Asp Lys Tyr Ala Asn Phe Thr Ile 
                245                 250                 255     


Asn Phe Thr Met Glu Asn Gln Ile His Thr Gly Met Glu Tyr Asp Asn 
            260                 265                 270         


Gly Arg Phe Ile Gly Val Lys Phe Lys Ser Val Thr Phe Lys Asp Ser 
        275                 280                 285             


Val Phe Lys Ser Cys Thr Phe Glu Asp Val Thr Ser Val Asn Thr Tyr 
    290                 295                 300                 


Phe Lys Asn Cys Thr Phe Ile Asp Thr Val Phe Asp Asn Thr Asp Phe 
305                 310                 315                 320 


Glu Pro Tyr Lys Phe Ile Asp Ser Glu Phe Lys Asn Cys Ser Phe Phe 
                325                 330                 335     


His Asn Lys Thr Gly Cys Gln Ile Thr Phe Asp Asp Asp Tyr Ser Ala 
            340                 345                 350         


Tyr Trp Ile Tyr Phe Val Asn Phe Leu Gly Thr Leu Ala Val Leu Pro 
        355                 360                 365             


Gly Asn Ile Val Ser Ala Leu Leu 
    370                 375     


<210>  2
<211>  150
<212>  PRT
<213>  Homo sapiens

<400>  2

Phe Pro Asp Val Ile Lys Pro Leu Gln Ser Asp Glu Tyr Ala Leu Leu 
1               5                   10                  15      


Thr Arg Asn Val Glu Arg Asp Lys Tyr Ala Asn Phe Thr Ile Asn Phe 
            20                  25                  30          


Thr Met Glu Asn Gln Ile His Thr Gly Met Glu Tyr Asp Asn Gly Arg 
        35                  40                  45              


Phe Ile Gly Val Lys Phe Lys Ser Val Thr Phe Lys Asp Ser Val Phe 
    50                  55                  60                  


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


Asn Cys Thr Phe Ile Asp Thr Val Phe Asp Asn Thr Asp Phe Glu Pro 
                85                  90                  95      


Tyr Lys Phe Ile Asp Ser Glu Phe Lys Asn Cys Ser Phe Phe His Asn 
            100                 105                 110         


Lys Thr Gly Cys Gln Ile Thr Phe Asp Asp Asp Tyr Ser Ala Tyr Trp 
        115                 120                 125             


Ile Tyr Phe Val Asn Phe Leu Gly Thr Leu Ala Val Leu Pro Gly Asn 
    130                 135                 140                 


Ile Val Ser Ala Leu Leu 
145                 150 


<210>  3
<211>  307
<212>  PRT
<213>  Artificial sequence

<220>
<223>  /note="Description of artificial sequence: fusion protein"

<400>  3

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


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


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


Gly Ser Val Ser Ala Ser His Pro Glu Ala Leu Ala Ala Pro Val Thr 
225                 230                 235                 240 


Thr Val Ala Thr Leu Val Pro His Asn Ala Thr Glu Pro Ala Ser Pro 
                245                 250                 255     


Gly Glu Gly Lys Glu Asp Ala Phe Ser Lys Leu Lys Gln Lys Phe Met 
            260                 265                 270         


Asn Glu Leu His Lys Ile Pro Leu Pro Pro Trp Ala Leu Ile Ala Ile 
        275                 280                 285             


Ala Ile Val Ala Val Leu Leu Val Val Thr Cys Cys Phe Cys Val Cys 
    290                 295                 300                 


Lys Lys Cys 
305         


<210>  4
<211>  82
<212>  PRT
<213>  Rattus norvegicus

<400>  4

Met Val Ser Ala Ser His Pro Glu Ala Leu Ala Ala Pro Val Thr Thr 
1               5                   10                  15      


Val Ala Thr Leu Val Pro His Asn Ala Thr Glu Pro Ala Ser Pro Gly 
            20                  25                  30          


Glu Gly Lys Glu Asp Ala Phe Ser Lys Leu Lys Gln Lys Phe Met Asn 
        35                  40                  45              


Glu Leu His Lys Ile Pro Leu Pro Pro Trp Ala Leu Ile Ala Ile Ala 
    50                  55                  60                  


Ile Val Ala Val Leu Leu Val Val Thr Cys Cys Phe Cys Val Cys Lys 
65                  70                  75                  80  


Lys Cys 
        


<210>  5
<211>  48
<212>  PRT
<213>  Rattus norvegicus

<400>  5

Lys Glu Asp Ala Phe Ser Lys Leu Lys Gln Lys Phe Met Asn Glu Leu 
1               5                   10                  15      


His Lys Ile Pro Leu Pro Pro Trp Ala Leu Ile Ala Ile Ala Ile Val 
            20                  25                  30          


Ala Val Leu Leu Val Val Thr Cys Cys Phe Cys Val Cys Lys Lys Cys 
        35                  40                  45              


<210>  6
<211>  316
<212>  PRT
<213>  Artificial sequence

<220>
<223>  /note="Description of artificial sequence: fusion protein"

<400>  6

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


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


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


Gly Ser Met Arg Asn Ile Phe Lys Arg Asn Gln Glu Pro Ile Val Ala 
225                 230                 235                 240 


Pro Ala Thr Thr Thr Ala Thr Met Pro Leu Ala Pro Ala Ala Pro Ala 
                245                 250                 255     


Asp Asn Ser Thr Glu Ser Thr Gly Thr Gly Glu Ser Gln Glu Asp Met 
            260                 265                 270         


Phe Ala Lys Leu Lys Asp Lys Phe Phe Asn Glu Ile Asn Lys Ile Pro 
        275                 280                 285             


Leu Pro Pro Trp Ala Leu Ile Ala Met Ala Val Val Ala Gly Leu Leu 
    290                 295                 300                 


Leu Leu Thr Cys Cys Phe Cys Ile Cys Lys Lys Cys 
305                 310                 315     


<210>  7
<211>  90
<212>  PRT
<213>  Rattus norvegicus

<400>  7

Met Arg Asn Ile Phe Lys Arg Asn Gln Glu Pro Ile Val Ala Pro Ala 
1               5                   10                  15      


Thr Thr Thr Ala Thr Met Pro Leu Ala Pro Ala Ala Pro Ala Asp Asn 
            20                  25                  30          


Ser Thr Glu Ser Thr Gly Thr Gly Glu Ser Gln Glu Asp Met Phe Ala 
        35                  40                  45              


Lys Leu Lys Asp Lys Phe Phe Asn Glu Ile Asn Lys Ile Pro Leu Pro 
    50                  55                  60                  


Pro Trp Ala Leu Ile Ala Met Ala Val Val Ala Gly Leu Leu Leu Leu 
65                  70                  75                  80  


Thr Cys Cys Phe Cys Ile Cys Lys Lys Cys 
                85                  90  


<210>  8
<211>  47
<212>  PRT
<213>  Rattus norvegicus

<400>  8

Glu Asp Met Phe Ala Lys Leu Lys Asp Lys Phe Phe Asn Glu Ile Asn 
1               5                   10                  15      


Lys Ile Pro Leu Pro Pro Trp Ala Leu Ile Ala Met Ala Val Val Ala 
            20                  25                  30          


Gly Leu Leu Leu Leu Thr Cys Cys Phe Cys Ile Cys Lys Lys Cys 
        35                  40                  45          


<210>  9
<211>  377
<212>  PRT
<213>  Artificial sequence

<220>
<223>  /note="Description of artificial sequence: fusion protein"

<400>  9

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


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


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


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


Arg Thr Lys Val Phe Pro Gly Glu Arg Val Glu His Val Thr Phe Asn 
                245                 250                 255     


Phe Thr Leu Glu Asn Gln Ile His Arg Gly Gly Gln Tyr Phe Asn Asp 
            260                 265                 270         


Lys Phe Ile Gly Leu Arg Leu Lys Ser Val Ser Phe Glu Asp Ser Leu 
        275                 280                 285             


Phe Glu Glu Cys Tyr Phe Glu Asp Val Thr Ser Ser Asn Thr Phe Phe 
    290                 295                 300                 


Arg Asn Cys Thr Phe Ile Asn Thr Val Phe Tyr Asn Thr Asp Leu Phe 
305                 310                 315                 320 


Glu Tyr Lys Phe Val Asn Ser Arg Leu Val Asn Ser Thr Phe Leu His 
                325                 330                 335     


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


Tyr Met Val Tyr Phe Val Ser Phe Leu Gly Thr Leu Ala Val Leu Pro 
        355                 360                 365             


Gly Asn Ile Val Ser Ala Leu Leu Met 
    370                 375         


<210>  10
<211>  151
<212>  PRT
<213>  Rattus norvegicus

<400>  10

Pro Asp Met Ile Arg His Leu Gln Ala Val Asp Tyr Ala Ala Arg Thr 
1               5                   10                  15      


Lys Val Phe Pro Gly Glu Arg Val Glu His Val Thr Phe Asn Phe Thr 
            20                  25                  30          


Leu Glu Asn Gln Ile His Arg Gly Gly Gln Tyr Phe Asn Asp Lys Phe 
        35                  40                  45              


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


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


Cys Thr Phe Ile Asn Thr Val Phe Tyr Asn Thr Asp Leu Phe Glu Tyr 
                85                  90                  95      


Lys Phe Val Asn Ser Arg Leu Val Asn Ser Thr Phe Leu His Asn Lys 
            100                 105                 110         


Glu Gly Cys Pro Leu Asp Val Thr Gly Thr Gly Glu Gly Ala Tyr Met 
        115                 120                 125             


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


Ile Val Ser Ala Leu Leu Met 
145                 150     


<210>  11
<211>  374
<212>  PRT
<213>  Artificial sequence

<220>
<223>  /note="Description of artificial sequence: fusion protein"

<400>  11

Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro 
1               5                   10                  15      


Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu 
            20                  25                  30          


Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu 
        35                  40                  45              


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


Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn 
65                  70                  75                  80  


Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu 
                85                  90                  95      


Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser 
            100                 105                 110         


Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu 
        115                 120                 125             


Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn 
    130                 135                 140                 


Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp 
145                 150                 155                 160 


Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu 
                165                 170                 175     


Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr 
            180                 185                 190         


Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala 
        195                 200                 205             


Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Asp Leu Val Pro Arg 
    210                 215                 220                 


Gly Ser Asp Met Ile Arg Tyr Phe Gln Asp Glu Glu Tyr Lys Ser Lys 
225                 230                 235                 240 


Met Lys Val Phe Phe Gly Glu His Val His Gly Ala Thr Ile Asn Phe 
                245                 250                 255     


Thr Met Glu Asn Gln Ile His Gln His Gly Lys Leu Val Asn Asp Lys 
            260                 265                 270         


Phe Ile Lys Met Tyr Phe Lys His Val Leu Phe Glu Asp Thr Phe Phe 
        275                 280                 285             


Asp Lys Cys Tyr Phe Glu Asp Val Thr Ser Thr Asp Thr Tyr Phe Lys 
    290                 295                 300                 


Asn Cys Thr Ile Glu Ser Thr Thr Phe Tyr Asn Thr Asp Leu Tyr Lys 
305                 310                 315                 320 


His Lys Phe Ile Asp Cys Arg Phe Ile Asn Ser Thr Phe Leu Glu Gln 
                325                 330                 335     


Lys Glu Gly Cys His Met Asp Phe Glu Glu Asp Asn Asp Phe Leu Ile 
            340                 345                 350         


Tyr Leu Val Ser Phe Leu Gly Ser Leu Ser Val Leu Pro Gly Asn Ile 
        355                 360                 365             


Ile Ser Ala Leu Leu Met 
    370                 


<210>  12
<211>  148
<212>  PRT
<213>  Rattus norvegicus

<400>  12

Asp Met Ile Arg Tyr Phe Gln Asp Glu Glu Tyr Lys Ser Lys Met Lys 
1               5                   10                  15      


Val Phe Phe Gly Glu His Val His Gly Ala Thr Ile Asn Phe Thr Met 
            20                  25                  30          


Glu Asn Gln Ile His Gln His Gly Lys Leu Val Asn Asp Lys Phe Ile 
        35                  40                  45              


Lys Met Tyr Phe Lys His Val Leu Phe Glu Asp Thr Phe Phe Asp Lys 
    50                  55                  60                  


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


Thr Ile Glu Ser Thr Thr Phe Tyr Asn Thr Asp Leu Tyr Lys His Lys 
                85                  90                  95      


Phe Ile Asp Cys Arg Phe Ile Asn Ser Thr Phe Leu Glu Gln Lys Glu 
            100                 105                 110         


Gly Cys His Met Asp Phe Glu Glu Asp Asn Asp Phe Leu Ile Tyr Leu 
        115                 120                 125             


Val Ser Phe Leu Gly Ser Leu Ser Val Leu Pro Gly Asn Ile Ile Ser 
    130                 135                 140                 


Ala Leu Leu Met 
145             


<210>  13
<211>  206
<212>  PRT
<213>  Rattus norvegicus

<400>  13

Met Ala Glu Asp Ala Asp Met Arg Asn Glu Leu Glu Glu Met Gln Arg 
1               5                   10                  15      


Arg Ala Asp Gln Leu Ala Asp Glu Ser Leu Glu Ser Thr Arg Arg Met 
            20                  25                  30          


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


Met Leu Asp Glu Gln Gly Glu Gln Leu Asp Arg Val Glu Glu Gly Met 
    50                  55                  60                  


Asn His Ile Asn Gln Asp Met Lys Glu Ala Glu Lys Asn Leu Lys Asp 
65                  70                  75                  80  


Leu Gly Lys Cys Cys Gly Leu Tyr Ile Cys Pro Cys Asn Lys Leu Lys 
                85                  90                  95      


Ser Ser Asp Ala Tyr Lys Lys Ala Trp Gly Asn Asn Gln Asp Gly Val 
            100                 105                 110         


Val Ala Ser Gln Pro Ala Arg Val Val Asp Glu Arg Glu Gln Met Ala 
        115                 120                 125             


Ile Ser Gly Gly Phe Ile Arg Arg Val Thr Asn Asp Ala Arg Glu Asn 
    130                 135                 140                 


Glu Met Asp Glu Asn Leu Glu Gln Val Ser Gly Ile Ile Gly Asn Leu 
145                 150                 155                 160 


Arg His Met Ala Leu Asp Met Gly Asn Glu Ile Asp Thr Gln Asn Arg 
                165                 170                 175     


Gln Ile Asp Arg Ile Met Glu Lys Ala Asp Ser Asn Lys Thr Arg Ile 
            180                 185                 190         


Asp Glu Ala Asn Gln Arg Ala Thr Lys Met Leu Gly Ser Gly 
        195                 200                 205     


<210>  14
<211>  67
<212>  PRT
<213>  Homo sapiens

<400>  14

Asp Ala Arg Glu Asn Glu Met Asp Glu Asn Leu Glu Gln Val Ser Gly 
1               5                   10                  15      


Ile Ile Gly Asn Leu Arg His Met Ala Leu Asp Met Gly Asn Glu Ile 
            20                  25                  30          


Asp Thr Gln Asn Arg Gln Ile Asp Arg Ile Met Glu Lys Ala Asp Ser 
        35                  40                  45              


Asn Lys Thr Arg Ile Asp Glu Ala Asn Gln Arg Ala Thr Lys Met Leu 
    50                  55                  60                  


Gly Ser Gly 
65          


<210>  15
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  15

Met Ser Ala Thr Ala Ala Thr Ala Pro Pro Ala Ala Pro Ala Gly Glu 
1               5                   10                  15      


Gly Gly Pro Pro Ala Pro Pro Pro Asn Leu Thr Ser Asn Arg Arg Leu 
            20                  25                  30          


Gln Gln Thr Gln Ala Gln Val Asp Glu Val Val Asp Ile Met Arg Val 
        35                  40                  45              


Asn Val Asp Lys Val Leu Glu Arg Asp Gln Lys Leu Ser Glu Leu Asp 
    50                  55                  60                  


Asp Arg Ala Asp Ala Leu Gln Ala Gly Ala Ser Gln Phe Glu Thr Ser 
65                  70                  75                  80  


Ala Ala Lys Leu Lys Arg Lys Tyr Trp Trp Lys Asn Leu Lys Met Met 
                85                  90                  95      


Ile Ile Leu Gly Val Ile Cys Ala Ile Ile Leu Ile Ile Ile Ile Val 
            100                 105                 110         


Tyr Phe Ser Thr 
        115     


<210>  16
<211>  116
<212>  PRT
<213>  Rattus norvegicus

<400>  16

Met Ser Ala Thr Ala Ala Thr Val Pro Pro Ala Ala Pro Ala Gly Glu 
1               5                   10                  15      


Gly Gly Pro Pro Ala Pro Pro Pro Asn Leu Thr Ser Asn Arg Arg Leu 
            20                  25                  30          


Gln Gln Thr Gln Ala Gln Val Asp Glu Val Val Asp Ile Met Arg Val 
        35                  40                  45              


Asn Val Asp Lys Val Leu Glu Arg Asp Gln Lys Leu Ser Glu Leu Asp 
    50                  55                  60                  


Asp Arg Ala Asp Ala Leu Gln Ala Gly Ala Ser Gln Phe Glu Thr Ser 
65                  70                  75                  80  


Ala Ala Lys Leu Lys Arg Lys Tyr Trp Trp Lys Asn Leu Lys Met Met 
                85                  90                  95      


Ile Ile Leu Gly Val Ile Cys Ala Ile Ile Leu Ile Ile Ile Ile Val 
            100                 105                 110         


Tyr Phe Ser Thr 
        115     


<210>  17
<211>  118
<212>  PRT
<213>  Rattus norvegicus

<400>  17

Met Ser Ala Pro Ala Gln Pro Pro Ala Glu Gly Thr Glu Gly Ala Ala 
1               5                   10                  15      


Pro Gly Gly Gly Pro Pro Gly Pro Pro Pro Asn Thr Thr Ser Asn Arg 
            20                  25                  30          


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


Arg Val Asn Val Asp Lys Val Leu Glu Arg Asp Gln Lys Leu Ser Glu 
    50                  55                  60                  


Leu Asp Asp Arg Ala Asp Ala Leu Gln Ala Gly Ala Ser Val Phe Glu 
65                  70                  75                  80  


Ser Ser Ala Ala Lys Leu Lys Arg Lys Tyr Trp Trp Lys Asn Cys Lys 
                85                  90                  95      


Met Met Ile Met Leu Gly Ala Ile Cys Ala Ile Ile Val Val Val Ile 
            100                 105                 110         


Val Ile Tyr Ile Phe Thr 
        115             


<210>  18
<211>  103
<212>  PRT
<213>  Rattus norvegicus

<400>  18

Met Ser Thr Gly Val Pro Ser Gly Ser Ser Ala Ala Thr Gly Ser Asn 
1               5                   10                  15      


Arg Arg Leu Gln Gln Thr Gln Asn Gln Val Asp Glu Val Val Asp Ile 
            20                  25                  30          


Met Arg Val Asn Val Asp Lys Val Leu Glu Arg Asp Gln Lys Leu Ser 
        35                  40                  45              


Glu Leu Asp Asp Arg Ala Asp Ala Leu Gln Ala Gly Ala Ser Gln Phe 
    50                  55                  60                  


Glu Thr Ser Ala Ala Lys Leu Lys Arg Lys Tyr Trp Trp Lys Asn Cys 
65                  70                  75                  80  


Lys Met Trp Ala Ile Gly Ile Ser Val Leu Val Ile Ile Val Ile Ile 
                85                  90                  95      


Ile Ile Val Trp Cys Val Ser 
            100             


<210>  19
<211>  288
<212>  PRT
<213>  Homo sapiens

<400>  19

Met Lys Asp Arg Thr Gln Glu Leu Arg Thr Ala Lys Asp Ser Asp Asp 
1               5                   10                  15      


Asp Asp Asp Val Ala Val Thr Val Asp Arg Asp Arg Phe Met Asp Glu 
            20                  25                  30          


Phe Phe Glu Gln Val Glu Glu Ile Arg Gly Phe Ile Asp Lys Ile Ala 
        35                  40                  45              


Glu Asn Val Glu Glu Val Lys Arg Lys His Ser Ala Ile Leu Ala Ser 
    50                  55                  60                  


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


Asp Ile Lys Lys Thr Ala Asn Lys Val Arg Ser Lys Leu Lys Ser Ile 
                85                  90                  95      


Glu Gln Ser Ile Glu Gln Glu Glu Gly Leu Asn Arg Ser Ser Ala Asp 
            100                 105                 110         


Leu Arg Ile Arg Lys Thr Gln His Ser Thr Leu Ser Arg Lys Phe Val 
        115                 120                 125             


Glu Val Met Ser Glu Tyr Asn Ala Thr Gln Ser Asp Tyr Arg Glu Arg 
    130                 135                 140                 


Cys Lys Gly Arg Ile Gln Arg Gln Leu Glu Ile Thr Gly Arg Thr Thr 
145                 150                 155                 160 


Thr Ser Glu Glu Leu Glu Asp Met Leu Glu Ser Gly Asn Pro Ala Ile 
                165                 170                 175     


Phe Ala Ser Gly Ile Ile Met Asp Ser Ser Ile Ser Lys Gln Ala Leu 
            180                 185                 190         


Ser Glu Ile Glu Thr Arg His Ser Glu Ile Ile Lys Leu Glu Asn Ser 
        195                 200                 205             


Ile Arg Glu Leu His Asp Met Phe Met Asp Met Ala Met Leu Val Glu 
    210                 215                 220                 


Ser Gln Gly Glu Met Ile Asp Arg Ile Glu Tyr Asn Val Glu His Ala 
225                 230                 235                 240 


Val Asp Tyr Val Glu Arg Ala Val Ser Asp Thr Lys Lys Ala Val Lys 
                245                 250                 255     


Tyr Gln Ser Lys Ala Arg Arg Lys Lys Ile Met Ile Ile Ile Cys Cys 
            260                 265                 270         


Val Ile Leu Gly Ile Val Ile Ala Ser Thr Val Gly Gly Ile Phe Ala 
        275                 280                 285             


<210>  20
<211>  288
<212>  PRT
<213>  Rattus norvegicus

<400>  20

Met Lys Asp Arg Thr Gln Glu Leu Arg Thr Ala Lys Asp Ser Asp Asp 
1               5                   10                  15      


Asp Asp Asp Val Thr Val Thr Val Asp Arg Asp Arg Phe Met Asp Glu 
            20                  25                  30          


Phe Phe Glu Gln Val Glu Glu Ile Arg Gly Phe Ile Asp Lys Ile Ala 
        35                  40                  45              


Glu Asn Val Glu Glu Val Lys Arg Lys His Ser Ala Ile Leu Ala Ser 
    50                  55                  60                  


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


Asp Ile Lys Lys Thr Ala Asn Lys Val Arg Ser Lys Leu Lys Ser Ile 
                85                  90                  95      


Glu Gln Ser Ile Glu Gln Glu Glu Gly Leu Asn Arg Ser Ser Ala Asp 
            100                 105                 110         


Leu Arg Ile Arg Lys Thr Gln His Ser Thr Leu Ser Arg Lys Phe Val 
        115                 120                 125             


Glu Val Met Ser Glu Tyr Asn Ala Thr Gln Ser Asp Tyr Arg Glu Arg 
    130                 135                 140                 


Cys Lys Gly Arg Ile Gln Arg Gln Leu Glu Ile Thr Gly Arg Thr Thr 
145                 150                 155                 160 


Thr Ser Glu Glu Leu Glu Asp Met Leu Glu Ser Gly Asn Pro Ala Ile 
                165                 170                 175     


Phe Ala Ser Gly Ile Ile Met Asp Ser Ser Ile Ser Lys Gln Ala Leu 
            180                 185                 190         


Ser Glu Ile Glu Thr Arg His Ser Glu Ile Ile Lys Leu Glu Asn Ser 
        195                 200                 205             


Ile Arg Glu Leu His Asp Met Phe Met Asp Met Ala Met Leu Val Glu 
    210                 215                 220                 


Ser Gln Gly Glu Met Ile Asp Arg Ile Glu Tyr Asn Val Glu His Ala 
225                 230                 235                 240 


Val Asp Tyr Val Glu Arg Ala Val Ser Asp Thr Lys Lys Ala Val Lys 
                245                 250                 255     


Tyr Gln Ser Lys Ala Arg Arg Lys Lys Ile Met Ile Ile Ile Cys Cys 
            260                 265                 270         


Val Ile Leu Gly Ile Ile Ile Ala Ser Thr Ile Gly Gly Ile Phe Gly 
        275                 280                 285             


<210>  21
<211>  288
<212>  PRT
<213>  Mus musculus

<400>  21

Met Lys Asp Arg Thr Gln Glu Leu Arg Thr Ala Lys Asp Ser Asp Asp 
1               5                   10                  15      


Asp Asp Asp Val Thr Val Thr Val Asp Arg Asp Arg Phe Met Asp Glu 
            20                  25                  30          


Phe Phe Glu Gln Val Glu Glu Ile Arg Gly Phe Ile Asp Lys Ile Ala 
        35                  40                  45              


Glu Asn Val Glu Glu Val Lys Arg Lys His Ser Ala Ile Leu Ala Ser 
    50                  55                  60                  


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


Asp Ile Lys Lys Thr Ala Asn Lys Val Arg Ser Lys Leu Lys Ser Ile 
                85                  90                  95      


Glu Gln Ser Ile Glu Gln Glu Glu Gly Leu Asn Arg Ser Ser Ala Asp 
            100                 105                 110         


Leu Arg Ile Arg Lys Thr Gln His Ser Thr Leu Ser Arg Lys Phe Val 
        115                 120                 125             


Glu Val Met Ser Glu Tyr Asn Ala Thr Gln Ser Asp Tyr Arg Glu Arg 
    130                 135                 140                 


Cys Lys Gly Arg Ile Gln Arg Gln Leu Glu Ile Thr Gly Arg Thr Thr 
145                 150                 155                 160 


Thr Ser Glu Glu Leu Glu Asp Met Leu Glu Ser Gly Asn Pro Ala Ile 
                165                 170                 175     


Phe Ala Ser Gly Ile Ile Met Asp Ser Ser Ile Ser Lys Gln Ala Leu 
            180                 185                 190         


Ser Glu Ile Glu Thr Arg His Ser Glu Ile Ile Lys Leu Glu Thr Ser 
        195                 200                 205             


Ile Arg Glu Leu His Asp Met Phe Met Asp Met Ala Met Leu Val Glu 
    210                 215                 220                 


Ser Gln Gly Glu Met Ile Asp Arg Ile Glu Tyr Asn Val Glu His Ala 
225                 230                 235                 240 


Val Asp Tyr Val Glu Arg Ala Val Ser Asp Thr Lys Lys Ala Val Lys 
                245                 250                 255     


Tyr Gln Ser Lys Ala Arg Arg Lys Lys Ile Met Ile Ile Ile Cys Cys 
            260                 265                 270         


Val Ile Leu Gly Ile Ile Ile Ala Ser Thr Ile Gly Gly Ile Phe Gly 
        275                 280                 285             


