                         SEQUENCE LISTING

<110>  Merz Pharma GmbH & Co.KGaA
 
<120>  Means and Methods for the determination of the biological activity of BoNT/E in cells

<130>  MP12918PC

<150>  EP 14199282.6

<151>  2014-12-19

<160>  22  

<170>  PatentIn version 3.5

<210>  1
<211>  13
<212>  PRT
<213>  Artificial
<220>  blank
<223>  BoNT/E epitope

<400>  1
Cys Asn Glu Ile Asp Thr Gln Asn Arg Gln Ile Asp Arg 



<210>  2
<211>  12
<212>  PRT
<213>  Homo sapiens

<400>  2
Asn Glu Ile Asp Thr Gln Asn Arg Gln Ile Asp Arg 




<210>  3
<211>  11
<212>  PRT
<213>  Homo sapiens

<400>  3
Glu Ile Asp Thr Gln Asn Arg Gln Ile Asp Arg 



<210>  4
<211>  10
<212>  PRT
<213>  Homo sapiens

<400>  4
Ile Asp Thr Gln Asn Arg Gln Ile Asp Arg  



<210>  5
<211>  9
<212>  PRT
<213>  Homo sapiens

<400>  5
Asp Thr Gln Asn Arg Gln Ile Asp Arg 



<210>  6
<211>  8
<212>  PRT
<213>  Homo sapiens

<400>  6
Thr Gln Asn Arg Gln Ile Asp Arg 




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

<400>  7
Gln Asn Arg Gln Ile Asp Arg 



<210>  8
<211>  6
<212>  PRT
<213>  Homo sapiens

<400>  8
Asn Arg Gln Ile Asp Arg 



<210>  9
<211>  3756
<212>  DNA
<213>  Clostridium botulinum

<400>  9
atgccaaaaa ttaatagttt taattataat gatcctgtta atgatagaac aattttatat       60

attaaaccag gcggttgtca agaattttat aaatcattta atattatgaa aaatatttgg      120

ataattccag agagaaatgt aattggtaca accccccaag attttcatcc gcctacttca      180

ttaaaaaatg gagatagtag ttattatgac cctaattatt tacaaagtga tgaagaaaag      240

gatagatttt taaaaatagt cacaaaaata tttaatagaa taaataataa tctttcagga      300

gggattttat tagaagaact gtcaaaagct aatccatatt tagggaatga taatactcca      360

gataatcaat tccatattgg tgatgcatca gcagttgaga ttaaattctc aaatggtagc      420

caagacatac tattacctaa tgttattata atgggagcag agcctgattt atttgaaact      480

aacagttcca atatttctct aagaaataat tatatgccaa gcaatcaccg ttttggatca      540

atagctatag taacattctc acctgaatat tcttttagat ttaatgataa ttgtatgaat      600

gaatttattc aagatcctgc tcttacatta atgcatgaat taatacattc attacatgga      660

ctatatgggg ctaaagggat tactacaaag tatactataa cacaaaaaca aaatccccta      720

ataacaaata taagaggtac aaatattgaa gaattcttaa cttttggagg tactgattta      780

aacattatta ctagtgctca gtccaatgat atctatacta atcttctagc tgattataaa      840

aaaatagcgt ctaaacttag caaagtacaa gtatctaatc cactacttaa tccttataaa      900

gatgtttttg aagcaaagta tggattagat aaagatgcta gcggaattta ttcggtaaat      960

ataaacaaat ttaatgatat ttttaaaaaa ttatacagct ttacggaatt tgatttacga     1020

actaaatttc aagttaaatg taggcaaact tatattggac agtataaata cttcaaactt     1080

tcaaacttgt taaatgattc tatttataat atatcagaag gctataatat aaataattta     1140

aaggtaaatt ttagaggaca gaatgcaaat ttaaatccta gaattattac accaattaca     1200

ggtagaggac tagtaaaaaa aatcattaga ttttgtaaaa atattgtttc tgtaaaaggc     1260

ataaggaaat caatatgtat cgaaataaat aatggtgagt tattttttgt ggcttccgag     1320

aatagttata atgatgataa tataaatact cctaaagaaa ttgacgatac agtaacttca     1380

aataataatt atgaaaatga tttagatcag gttattttaa attttaatag tgaatcagca     1440

cctggacttt cagatgaaaa attaaattta actatccaaa atgatgctta tataccaaaa     1500

tatgattcta atggaacaag tgatatagaa caacatgatg ttaatgaact taatgtattt     1560

ttctatttag atgcacagaa agtgcccgaa ggtgaaaata atgtcaatct cacctcttca     1620

attgatacag cattattaga acaacctaaa atatatacat ttttttcatc agaatttatt     1680

aataatgtca ataaacctgt gcaagcagca ttatttgtaa gctggataca acaagtgtta     1740

gtagatttta ctactgaagc taaccaaaaa agtactgttg ataaaattgc agatatttct     1800

atagttgttc catatatagg tcttgcttta aatataggaa atgaagcaca aaaaggaaat     1860

tttaaagatg cacttgaatt attaggagca ggtattttat tagaatttga acccgagctt     1920

ttaattccta caattttagt attcacgata aaatcttttt taggttcatc tgataataaa     1980

aataaagtta ttaaagcaat aaataatgca ttgaaagaaa gagatgaaaa atggaaagaa     2040

gtatatagtt ttatagtatc gaattggatg actaaaatta atacacaatt taataaaaga     2100

aaagaacaaa tgtatcaagc tttacaaaat caagtaaatg caattaaaac aataatagaa     2160

tctaagtata atagttatac tttagaggaa aaaaatgagc ttacaaataa atatgatatt     2220

aagcaaatag aaaatgaact taatcaaaag gtttctatag caatgaataa tatagacagg     2280

ttcttaactg aaagttctat atcctattta atgaaaataa taaatgaagt aaaaattaat     2340

aaattaagag aatatgatga gaatgtcaaa acgtatttat tgaattatat tatacaacat     2400

ggatcaatct tgggagagag tcagcaagaa ctaaattcta tggtaactga taccctaaat     2460

aatagtattc cttttaagct ttcttcttat acagatgata aaattttaat ttcatatttt     2520

aataaattct ttaagagaat taaaagtagt tcagttttaa atatgagata taaaaatgat     2580

aaatacgtag atacttcagg atatgattca aatataaata ttaatggaga tgtatataaa     2640

tatccaacta ataaaaatca atttggaata tataatgata aacttagtga agttaatata     2700

tctcaaaatg attacattat atatgataat aaatataaaa attttagtat tagtttttgg     2760

gtaagaattc ctaactatga taataagata gtaaatgtta ataatgaata cactataata     2820

aattgtatga gagataataa ttcaggatgg aaagtatctc ttaatcataa tgaaataatt     2880

tggacattcg aagataatcg aggaattaat caaaaattag catttaacta tggtaacgca     2940

aatggtattt ctgattatat aaataagtgg atttttgtaa ctataactaa tgatagatta     3000

ggagattcta aactttatat taatggaaat ttaatagatc aaaaatcaat tttaaattta     3060

ggtaatattc atgttagtga caatatatta tttaaaatag ttaattgtag ttatacaaga     3120

tatattggta ttagatattt taatattttt gataaagaat tagatgaaac agaaattcaa     3180

actttatata gcaatgaacc taatacaaat attttgaagg atttttgggg aaattatttg     3240

ctttatgaca aagaatacta tttattaaat gtgttaaaac caaataactt tattgatagg     3300

agaaaagatt ctactttaag cattaataat ataagaagca ctattctttt agctaataga     3360

ttatatagtg gaataaaagt taaaatacaa agagttaata atagtagtac taacgataat     3420

cttgttagaa agaatgatca ggtatatatt aattttgtag ccagcaaaac tcacttattt     3480

ccattatatg ctgatacagc taccacaaat aaagagaaaa caataaaaat atcatcatct     3540

ggcaatagat ttaatcaagt agtagttatg aattcagtag gaaattgtac aatgaatttt     3600

aaaaataata atggaaataa tattgggttg ttaggtttca aggcagatac tgtcgttgct     3660

agtacttggt attatacaca tatgagagat catacaaaca gcaatggatg tttttggaac     3720

tttatttctg aagaacatgg atggcaagaa aaataa                               3756


<210>  10
<211>  1251
<212>  PRT
<213>  Clostridium botulinum

<400>  10

Met Pro Lys Ile Asn Ser Phe Asn Tyr Asn Asp Pro Val Asn Asp Arg 
1               5                   10                  15      


Thr Ile Leu Tyr Ile Lys Pro Gly Gly Cys Gln Glu Phe Tyr Lys Ser 
            20                  25                  30          


Phe Asn Ile Met Lys Asn Ile Trp Ile Ile Pro Glu Arg Asn Val Ile 
        35                  40                  45              


Gly Thr Thr Pro Gln Asp Phe His Pro Pro Thr Ser Leu Lys Asn Gly 
    50                  55                  60                  


Asp Ser Ser Tyr Tyr Asp Pro Asn Tyr Leu Gln Ser Asp Glu Glu Lys 
65                  70                  75                  80  


Asp Arg Phe Leu Lys Ile Val Thr Lys Ile Phe Asn Arg Ile Asn Asn 
                85                  90                  95      


Asn Leu Ser Gly Gly Ile Leu Leu Glu Glu Leu Ser Lys Ala Asn Pro 
            100                 105                 110         


Tyr Leu Gly Asn Asp Asn Thr Pro Asp Asn Gln Phe His Ile Gly Asp 
        115                 120                 125             


Ala Ser Ala Val Glu Ile Lys Phe Ser Asn Gly Ser Gln Asp Ile Leu 
    130                 135                 140                 


Leu Pro Asn Val Ile Ile Met Gly Ala Glu Pro Asp Leu Phe Glu Thr 
145                 150                 155                 160 


Asn Ser Ser Asn Ile Ser Leu Arg Asn Asn Tyr Met Pro Ser Asn His 
                165                 170                 175     


Arg Phe Gly Ser Ile Ala Ile Val Thr Phe Ser Pro Glu Tyr Ser Phe 
            180                 185                 190         


Arg Phe Asn Asp Asn Cys Met Asn Glu Phe Ile Gln Asp Pro Ala Leu 
        195                 200                 205             


Thr Leu Met His Glu Leu Ile His Ser Leu His Gly Leu Tyr Gly Ala 
    210                 215                 220                 


Lys Gly Ile Thr Thr Lys Tyr Thr Ile Thr Gln Lys Gln Asn Pro Leu 
225                 230                 235                 240 


Ile Thr Asn Ile Arg Gly Thr Asn Ile Glu Glu Phe Leu Thr Phe Gly 
                245                 250                 255     


Gly Thr Asp Leu Asn Ile Ile Thr Ser Ala Gln Ser Asn Asp Ile Tyr 
            260                 265                 270         


Thr Asn Leu Leu Ala Asp Tyr Lys Lys Ile Ala Ser Lys Leu Ser Lys 
        275                 280                 285             


Val Gln Val Ser Asn Pro Leu Leu Asn Pro Tyr Lys Asp Val Phe Glu 
    290                 295                 300                 


Ala Lys Tyr Gly Leu Asp Lys Asp Ala Ser Gly Ile Tyr Ser Val Asn 
305                 310                 315                 320 


Ile Asn Lys Phe Asn Asp Ile Phe Lys Lys Leu Tyr Ser Phe Thr Glu 
                325                 330                 335     


Phe Asp Leu Arg Thr Lys Phe Gln Val Lys Cys Arg Gln Thr Tyr Ile 
            340                 345                 350         


Gly Gln Tyr Lys Tyr Phe Lys Leu Ser Asn Leu Leu Asn Asp Ser Ile 
        355                 360                 365             


Tyr Asn Ile Ser Glu Gly Tyr Asn Ile Asn Asn Leu Lys Val Asn Phe 
    370                 375                 380                 


Arg Gly Gln Asn Ala Asn Leu Asn Pro Arg Ile Ile Thr Pro Ile Thr 
385                 390                 395                 400 


Gly Arg Gly Leu Val Lys Lys Ile Ile Arg Phe Cys Lys Asn Ile Val 
                405                 410                 415     


Ser Val Lys Gly Ile Arg Lys Ser Ile Cys Ile Glu Ile Asn Asn Gly 
            420                 425                 430         


Glu Leu Phe Phe Val Ala Ser Glu Asn Ser Tyr Asn Asp Asp Asn Ile 
        435                 440                 445             


Asn Thr Pro Lys Glu Ile Asp Asp Thr Val Thr Ser Asn Asn Asn Tyr 
    450                 455                 460                 


Glu Asn Asp Leu Asp Gln Val Ile Leu Asn Phe Asn Ser Glu Ser Ala 
465                 470                 475                 480 


Pro Gly Leu Ser Asp Glu Lys Leu Asn Leu Thr Ile Gln Asn Asp Ala 
                485                 490                 495     


Tyr Ile Pro Lys Tyr Asp Ser Asn Gly Thr Ser Asp Ile Glu Gln His 
            500                 505                 510         


Asp Val Asn Glu Leu Asn Val Phe Phe Tyr Leu Asp Ala Gln Lys Val 
        515                 520                 525             


Pro Glu Gly Glu Asn Asn Val Asn Leu Thr Ser Ser Ile Asp Thr Ala 
    530                 535                 540                 


Leu Leu Glu Gln Pro Lys Ile Tyr Thr Phe Phe Ser Ser Glu Phe Ile 
545                 550                 555                 560 


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


Gln Gln Val Leu Val Asp Phe Thr Thr Glu Ala Asn Gln Lys Ser Thr 
            580                 585                 590         


Val Asp Lys Ile Ala Asp Ile Ser Ile Val Val Pro Tyr Ile Gly Leu 
        595                 600                 605             


Ala Leu Asn Ile Gly Asn Glu Ala Gln Lys Gly Asn Phe Lys Asp Ala 
    610                 615                 620                 


Leu Glu Leu Leu Gly Ala Gly Ile Leu Leu Glu Phe Glu Pro Glu Leu 
625                 630                 635                 640 


Leu Ile Pro Thr Ile Leu Val Phe Thr Ile Lys Ser Phe Leu Gly Ser 
                645                 650                 655     


Ser Asp Asn Lys Asn Lys Val Ile Lys Ala Ile Asn Asn Ala Leu Lys 
            660                 665                 670         


Glu Arg Asp Glu Lys Trp Lys Glu Val Tyr Ser Phe Ile Val Ser Asn 
        675                 680                 685             


Trp Met Thr Lys Ile Asn Thr Gln Phe Asn Lys Arg Lys Glu Gln Met 
    690                 695                 700                 


Tyr Gln Ala Leu Gln Asn Gln Val Asn Ala Ile Lys Thr Ile Ile Glu 
705                 710                 715                 720 


Ser Lys Tyr Asn Ser Tyr Thr Leu Glu Glu Lys Asn Glu Leu Thr Asn 
                725                 730                 735     


Lys Tyr Asp Ile Lys Gln Ile Glu Asn Glu Leu Asn Gln Lys Val Ser 
            740                 745                 750         


Ile Ala Met Asn Asn Ile Asp Arg Phe Leu Thr Glu Ser Ser Ile Ser 
        755                 760                 765             


Tyr Leu Met Lys Ile Ile Asn Glu Val Lys Ile Asn Lys Leu Arg Glu 
    770                 775                 780                 


Tyr Asp Glu Asn Val Lys Thr Tyr Leu Leu Asn Tyr Ile Ile Gln His 
785                 790                 795                 800 


Gly Ser Ile Leu Gly Glu Ser Gln Gln Glu Leu Asn Ser Met Val Thr 
                805                 810                 815     


Asp Thr Leu Asn Asn Ser Ile Pro Phe Lys Leu Ser Ser Tyr Thr Asp 
            820                 825                 830         


Asp Lys Ile Leu Ile Ser Tyr Phe Asn Lys Phe Phe Lys Arg Ile Lys 
        835                 840                 845             


Ser Ser Ser Val Leu Asn Met Arg Tyr Lys Asn Asp Lys Tyr Val Asp 
    850                 855                 860                 


Thr Ser Gly Tyr Asp Ser Asn Ile Asn Ile Asn Gly Asp Val Tyr Lys 
865                 870                 875                 880 


Tyr Pro Thr Asn Lys Asn Gln Phe Gly Ile Tyr Asn Asp Lys Leu Ser 
                885                 890                 895     


Glu Val Asn Ile Ser Gln Asn Asp Tyr Ile Ile Tyr Asp Asn Lys Tyr 
            900                 905                 910         


Lys Asn Phe Ser Ile Ser Phe Trp Val Arg Ile Pro Asn Tyr Asp Asn 
        915                 920                 925             


Lys Ile Val Asn Val Asn Asn Glu Tyr Thr Ile Ile Asn Cys Met Arg 
    930                 935                 940                 


Asp Asn Asn Ser Gly Trp Lys Val Ser Leu Asn His Asn Glu Ile Ile 
945                 950                 955                 960 


Trp Thr Phe Glu Asp Asn Arg Gly Ile Asn Gln Lys Leu Ala Phe Asn 
                965                 970                 975     


Tyr Gly Asn Ala Asn Gly Ile Ser Asp Tyr Ile Asn Lys Trp Ile Phe 
            980                 985                 990         


Val Thr Ile Thr Asn Asp Arg Leu  Gly Asp Ser Lys Leu  Tyr Ile Asn 
        995                 1000                 1005             


Gly Asn  Leu Ile Asp Gln Lys  Ser Ile Leu Asn Leu  Gly Asn Ile 
    1010                 1015                 1020             


His Val  Ser Asp Asn Ile Leu  Phe Lys Ile Val Asn  Cys Ser Tyr 
    1025                 1030                 1035             


Thr Arg  Tyr Ile Gly Ile Arg  Tyr Phe Asn Ile Phe  Asp Lys Glu 
    1040                 1045                 1050             


Leu Asp  Glu Thr Glu Ile Gln  Thr Leu Tyr Ser Asn  Glu Pro Asn 
    1055                 1060                 1065             


Thr Asn  Ile Leu Lys Asp Phe  Trp Gly Asn Tyr Leu  Leu Tyr Asp 
    1070                 1075                 1080             


Lys Glu  Tyr Tyr Leu Leu Asn  Val Leu Lys Pro Asn  Asn Phe Ile 
    1085                 1090                 1095             


Asp Arg  Arg Lys Asp Ser Thr  Leu Ser Ile Asn Asn  Ile Arg Ser 
    1100                 1105                 1110             


Thr Ile  Leu Leu Ala Asn Arg  Leu Tyr Ser Gly Ile  Lys Val Lys 
    1115                 1120                 1125             


Ile Gln  Arg Val Asn Asn Ser  Ser Thr Asn Asp Asn  Leu Val Arg 
    1130                 1135                 1140             


Lys Asn  Asp Gln Val Tyr Ile  Asn Phe Val Ala Ser  Lys Thr His 
    1145                 1150                 1155             


Leu Phe  Pro Leu Tyr Ala Asp  Thr Ala Thr Thr Asn  Lys Glu Lys 
    1160                 1165                 1170             


Thr Ile  Lys Ile Ser Ser Ser  Gly Asn Arg Phe Asn  Gln Val Val 
    1175                 1180                 1185             


Val Met  Asn Ser Val Gly Asn  Cys Thr Met Asn Phe  Lys Asn Asn 
    1190                 1195                 1200             


Asn Gly  Asn Asn Ile Gly Leu  Leu Gly Phe Lys Ala  Asp Thr Val 
    1205                 1210                 1215             


Val Ala  Ser Thr Trp Tyr Tyr  Thr His Met Arg Asp  His Thr Asn 
    1220                 1225                 1230             


Ser Asn  Gly Cys Phe Trp Asn  Phe Ile Ser Glu Glu  His Gly Trp 
    1235                 1240                 1245             


Gln Glu  Lys 
    1250     





<210>  11
<211>  3819
<212>  DNA
<213>  Artificial 

<220>
<223>  recombinant protein BONT/E with MDM2 binding motif


<400>  11
atgccgaaaa tcaacagctt caactataac gatccggtga acgatcgtac catcctgtat     60

attaaaccgg gcggttgcca ggaattttac aaaagcttca acatcatgaa aaacatctgg    120

attattccgg aacgtaacgt gattggcacc accccgcagg attttcatcc gccgaccagc    180

ctgaaaaacg gcgatagcag ctattatgat ccgaactatc tgcagtctga tgaagaaaaa    240

gatcgcttcc tgaaaatcgt gaccaaaatc ttcaaccgca tcaacaacaa cctgagcggc    300

ggcattctgc tggaagaact gagcaaagcg aatccgtatc tgggcaacga taacactcca    360

gataaccagt ttcatattgg tgatgcgagc gcggtggaaa ttaaatttag caacggctct    420

caggacattc tgctgccgaa cgtgattatt atgggcgcgg aaccggacct gtttgaaacc    480

aacagcagca acattagcct gcgtaacaac tatatgccga gcaaccatgg ttttggcagc    540

attgcgattg tgacctttag cccggaatat agctttcgct tcaacgataa cagcatgaac    600

gaatttattc aggacccggc gctgaccctg atgcacgagc tgattcatag cctgcatggc    660

ctgtatggcg cgaaaggcat taccaccaaa tataccatca cccagaaaca gaatccgctg    720

attaccaaca ttcgtggcac caacattgaa gaatttctga cctttggcgg caccgatctg    780

aacattatta ccagcgcgca gagcaacgat atctatacca acctgctggc cgattataaa    840

aaaatcgcgt ctaaactgag caaagtgcag gtgagcaatc cgctgctgaa tccgtataaa    900

gatgtgtttg aagcgaaata tggcctggat aaagatgcta gcggcattta tagcgtgaac    960

atcaacaaat tcaacgacat cttcaaaaaa ctgtatagct ttaccgaatt tgatctggcc   1020

accaaatttc aggtgaaatg ccgccagacc tatattggcc agtataaata ttttaaactg   1080

agcaacctgc tgaacgatag catttacaac atcagcgaag gctataacat caacaacctg   1140

aaagtgaact ttcgtggcca gaacgcgaat ttaaatccgc gtattattac cccgattacc   1200

ggccgtggac tagtgaaaaa aattatccgt ttttgcgtgc gtggcattat caccagcctg   1260

acctttgaac ataattgggc acagctgacc agcaaaagcc tggtgccgcg tggcagcaaa   1320

gcgttaaatg atttatgcat cgaaatcaac aacggcgaac tgttttttgt ggcgagcgaa   1380

aacagctata acgatgataa catcaacacc ccgaaagaaa ttgatgatac cgtgaccagc   1440

aataacaact acgaaaacga tctggatcag gtgattctga actttaacag cgaaagcgca   1500

ccgggcctgt ctgatgaaaa actgaacctg accattcaga acgatgcgta tatcccgaaa   1560

tatgatagca acggcaccag cgatattgaa cagcatgatg tgaacgaact gaacgtgttt   1620

ttttatctgg atgcgcagaa agtgccggaa ggcgaaaaca acgtgaatct gaccagctca   1680

attgataccg cgctgctgga acagccgaaa atctatacct tttttagcag cgaattcatc   1740

aacaacgtga acaaaccggt gcaggcggcg ctgtttgtga gctggattca gcaggtgctg   1800

gttgatttta ccaccgaagc gaaccagaaa agcaccgtgg ataaaattgc ggatattagc   1860

attgtggtgc cgtatattgg cctggccctg aacattggca acgaagcgca gaaaggcaac   1920

tttaaagatg cgctggaact gctgggtgcg ggcattctgc tggaatttga accggaactg   1980

ctgattccga ccattctggt gtttaccatc aaaagctttc tgggcagcag cgataacaaa   2040

aacaaagtga tcaaagcgat taacaacgcg ctgaaagaac gtgatgaaaa atggaaagaa   2100

gtgtatagct tcattgtgtc taactggatg accaaaatca acacccagtt caacaaacgt   2160

aaagaacaaa tgtatcaggc gctgcagaac caggtgaacg cgattaaaac catcatcgaa   2220

agcaaataca acagctacac cctggaagaa aaaaacgaac tgaccaacaa atatgacatc   2280

aaacaaatcg aaaatgaact gaaccagaaa gtgagcattg ccatgaacaa cattgatcgc   2340

tttctgaccg aaagcagcat tagctacctg atgaaactga tcaacgaagt gaaaatcaac   2400

aaactgcgcg aatatgatga aaacgtgaaa acctacctgc tgaactatat tattcagcat   2460

ggcagcattc tgggcgaaag ccagcaagaa ctgaacagca tggttaccga taccctgaac   2520

aacagcattc cgtttaaact gagcagctac accgatgata aaatcctgat cagctacttc   2580

aacaaattct tcaaacgcat caaaagcagc agcgtgctga acatgcgtta taaaaacgat   2640

aaatacgtag ataccagcgg ctatgatagc aatatcaaca ttaacggtga tgtgtataaa   2700

tacccgacca acaaaaacca gttcggcatc tacaacgata aactgagcga agtgaacatt   2760

agccagaacg attatatcat ctacgataat aaatataaaa acttcagcat cagcttttgg   2820

gtgcgtattc cgaactacga taacaaaatc gtgaacgtga acaacgaata caccatcatt   2880

aactgcatgc gtgataacaa cagcggctgg aaagtgagcc tgaaccataa cgaaatcatc   2940

tggaccctgc aggataacgc cggcattaac cagaaactgg cctttaacta tggcaacgcg   3000

aacggcatta gcgattacat caacaaatgg atctttgtga ccattaccaa cgatcgtctg   3060

ggcgatagca aactgtatat taacggcaac ctgatcgacc agaaaagcat tctgaacctg   3120

ggcaacattc atgtgagcga taacatcctg ttcaaaattg tgaactgcag ctatacccgt   3180

tatattggca tccgctattt caacatcttc gataaagaac tggatgaaac cgaaattcag   3240

accctgtata gcaacgaacc gaacaccaac atcctgaaag atttctgggg caactatctg   3300

ctgtacgata aagaatatta tctgctgaac gtgctgaaac cgaacaactt tattgatcgc   3360

cgtaaagata gcaccctgag cattaacaac attcgtagca ccattctgct ggccaaccgt   3420

ctgtatagcg gcattaaagt gaaaattcag cgcgtgaaca atagcagcac caacgataac   3480

ctggtgcgta aaaacgatca ggtgtatatc aactttgtgg ccagcaaaac ccacctgttt   3540

ccgctgtatg cggataccgc gaccaccaac aaagaaaaaa ccattaaaat cagcagcagc   3600

ggcaaccgtt ttaaccaggt ggtggtgatg aacagcgtgg gcaacaactg tacaatgaac   3660

ttcaaaaaca acaacggcaa caacattggc ctgctgggct ttaaagcgga taccgtggtg   3720

gcgagcacct ggtattatac ccacatgcgt gatcatacca acagcaacgg ctgcttttgg   3780

aactttatta gcgaagaaca tggctggcag gaaaaatga                          3819




<210>  12
<211>  1272
<212>  PRT
<213>  artificial

<220>
<223>  recombinant protein BONT/E with MDM2 binding motif

<400>  12

Met Pro Lys Ile Asn Ser Phe Asn Tyr Asn Asp Pro Val Asn Asp Arg 
1               5                   10                  15      


Thr Ile Leu Tyr Ile Lys Pro Gly Gly Cys Gln Glu Phe Tyr Lys Ser 
            20                  25                  30          


Phe Asn Ile Met Lys Asn Ile Trp Ile Ile Pro Glu Arg Asn Val Ile 
        35                  40                  45              


Gly Thr Thr Pro Gln Asp Phe His Pro Pro Thr Ser Leu Lys Asn Gly 
    50                  55                  60                  


Asp Ser Ser Tyr Tyr Asp Pro Asn Tyr Leu Gln Ser Asp Glu Glu Lys 
65                  70                  75                  80  


Asp Arg Phe Leu Lys Ile Val Thr Lys Ile Phe Asn Arg Ile Asn Asn 
                85                  90                  95      


Asn Leu Ser Gly Gly Ile Leu Leu Glu Glu Leu Ser Lys Ala Asn Pro 
            100                 105                 110         


Tyr Leu Gly Asn Asp Asn Thr Pro Asp Asn Gln Phe His Ile Gly Asp 
        115                 120                 125             


Ala Ser Ala Val Glu Ile Lys Phe Ser Asn Gly Ser Gln Asp Ile Leu 
    130                 135                 140                 


Leu Pro Asn Val Ile Ile Met Gly Ala Glu Pro Asp Leu Phe Glu Thr 
145                 150                 155                 160 


Asn Ser Ser Asn Ile Ser Leu Arg Asn Asn Tyr Met Pro Ser Asn His 
                165                 170                 175     


Gly Phe Gly Ser Ile Ala Ile Val Thr Phe Ser Pro Glu Tyr Ser Phe 
            180                 185                 190         


Arg Phe Asn Asp Asn Ser Met Asn Glu Phe Ile Gln Asp Pro Ala Leu 
        195                 200                 205             


Thr Leu Met His Glu Leu Ile His Ser Leu His Gly Leu Tyr Gly Ala 
    210                 215                 220                 


Lys Gly Ile Thr Thr Lys Tyr Thr Ile Thr Gln Lys Gln Asn Pro Leu 
225                 230                 235                 240 


Ile Thr Asn Ile Arg Gly Thr Asn Ile Glu Glu Phe Leu Thr Phe Gly 
                245                 250                 255     


Gly Thr Asp Leu Asn Ile Ile Thr Ser Ala Gln Ser Asn Asp Ile Tyr 
            260                 265                 270         


Thr Asn Leu Leu Ala Asp Tyr Lys Lys Ile Ala Ser Lys Leu Ser Lys 
        275                 280                 285             


Val Gln Val Ser Asn Pro Leu Leu Asn Pro Tyr Lys Asp Val Phe Glu 
    290                 295                 300                 


Ala Lys Tyr Gly Leu Asp Lys Asp Ala Ser Gly Ile Tyr Ser Val Asn 
305                 310                 315                 320 


Ile Asn Lys Phe Asn Asp Ile Phe Lys Lys Leu Tyr Ser Phe Thr Glu 
                325                 330                 335     


Phe Asp Leu Ala Thr Lys Phe Gln Val Lys Cys Arg Gln Thr Tyr Ile 
            340                 345                 350         


Gly Gln Tyr Lys Tyr Phe Lys Leu Ser Asn Leu Leu Asn Asp Ser Ile 
        355                 360                 365             


Tyr Asn Ile Ser Glu Gly Tyr Asn Ile Asn Asn Leu Lys Val Asn Phe 
    370                 375                 380                 


Arg Gly Gln Asn Ala Asn Leu Asn Pro Arg Ile Ile Thr Pro Ile Thr 
385                 390                 395                 400 


Gly Arg Gly Leu Val Lys Lys Ile Ile Arg Phe Cys Val Arg Gly Ile 
                405                 410                 415     


Ile Thr Ser Leu Thr Phe Glu His Asn Trp Ala Gln Leu Thr Ser Lys 
            420                 425                 430         


Ser Leu Val Pro Arg Gly Ser Lys Ala Leu Asn Asp Leu Cys Ile Glu 
        435                 440                 445             


Ile Asn Asn Gly Glu Leu Phe Phe Val Ala Ser Glu Asn Ser Tyr Asn 
    450                 455                 460                 


Asp Asp Asn Ile Asn Thr Pro Lys Glu Ile Asp Asp Thr Val Thr Ser 
465                 470                 475                 480 


Asn Asn Asn Tyr Glu Asn Asp Leu Asp Gln Val Ile Leu Asn Phe Asn 
                485                 490                 495     


Ser Glu Ser Ala Pro Gly Leu Ser Asp Glu Lys Leu Asn Leu Thr Ile 
            500                 505                 510         


Gln Asn Asp Ala Tyr Ile Pro Lys Tyr Asp Ser Asn Gly Thr Ser Asp 
        515                 520                 525             


Ile Glu Gln His Asp Val Asn Glu Leu Asn Val Phe Phe Tyr Leu Asp 
    530                 535                 540                 


Ala Gln Lys Val Pro Glu Gly Glu Asn Asn Val Asn Leu Thr Ser Ser 
545                 550                 555                 560 


Ile Asp Thr Ala Leu Leu Glu Gln Pro Lys Ile Tyr Thr Phe Phe Ser 
                565                 570                 575     


Ser Glu Phe Ile Asn Asn Val Asn Lys Pro Val Gln Ala Ala Leu Phe 
            580                 585                 590         


Val Ser Trp Ile Gln Gln Val Leu Val Asp Phe Thr Thr Glu Ala Asn 
        595                 600                 605             


Gln Lys Ser Thr Val Asp Lys Ile Ala Asp Ile Ser Ile Val Val Pro 
    610                 615                 620                 


Tyr Ile Gly Leu Ala Leu Asn Ile Gly Asn Glu Ala Gln Lys Gly Asn 
625                 630                 635                 640 


Phe Lys Asp Ala Leu Glu Leu Leu Gly Ala Gly Ile Leu Leu Glu Phe 
                645                 650                 655     


Glu Pro Glu Leu Leu Ile Pro Thr Ile Leu Val Phe Thr Ile Lys Ser 
            660                 665                 670         


Phe Leu Gly Ser Ser Asp Asn Lys Asn Lys Val Ile Lys Ala Ile Asn 
        675                 680                 685             


Asn Ala Leu Lys Glu Arg Asp Glu Lys Trp Lys Glu Val Tyr Ser Phe 
    690                 695                 700                 


Ile Val Ser Asn Trp Met Thr Lys Ile Asn Thr Gln Phe Asn Lys Arg 
705                 710                 715                 720 


Lys Glu Gln Met Tyr Gln Ala Leu Gln Asn Gln Val Asn Ala Ile Lys 
                725                 730                 735     


Thr Ile Ile Glu Ser Lys Tyr Asn Ser Tyr Thr Leu Glu Glu Lys Asn 
            740                 745                 750         


Glu Leu Thr Asn Lys Tyr Asp Ile Lys Gln Ile Glu Asn Glu Leu Asn 
        755                 760                 765             


Gln Lys Val Ser Ile Ala Met Asn Asn Ile Asp Arg Phe Leu Thr Glu 
    770                 775                 780                 


Ser Ser Ile Ser Tyr Leu Met Lys Leu Ile Asn Glu Val Lys Ile Asn 
785                 790                 795                 800 


Lys Leu Arg Glu Tyr Asp Glu Asn Val Lys Thr Tyr Leu Leu Asn Tyr 
                805                 810                 815     


Ile Ile Gln His Gly Ser Ile Leu Gly Glu Ser Gln Gln Glu Leu Asn 
            820                 825                 830         


Ser Met Val Thr Asp Thr Leu Asn Asn Ser Ile Pro Phe Lys Leu Ser 
        835                 840                 845             


Ser Tyr Thr Asp Asp Lys Ile Leu Ile Ser Tyr Phe Asn Lys Phe Phe 
    850                 855                 860                 


Lys Arg Ile Lys Ser Ser Ser Val Leu Asn Met Arg Tyr Lys Asn Asp 
865                 870                 875                 880 


Lys Tyr Val Asp Thr Ser Gly Tyr Asp Ser Asn Ile Asn Ile Asn Gly 
                885                 890                 895     


Asp Val Tyr Lys Tyr Pro Thr Asn Lys Asn Gln Phe Gly Ile Tyr Asn 
            900                 905                 910         


Asp Lys Leu Ser Glu Val Asn Ile Ser Gln Asn Asp Tyr Ile Ile Tyr 
        915                 920                 925             


Asp Asn Lys Tyr Lys Asn Phe Ser Ile Ser Phe Trp Val Arg Ile Pro 
    930                 935                 940                 


Asn Tyr Asp Asn Lys Ile Val Asn Val Asn Asn Glu Tyr Thr Ile Ile 
945                 950                 955                 960 


Asn Cys Met Arg Asp Asn Asn Ser Gly Trp Lys Val Ser Leu Asn His 
                965                 970                 975     


Asn Glu Ile Ile Trp Thr Leu Gln Asp Asn Ala Gly Ile Asn Gln Lys 
            980                 985                 990         


Leu Ala Phe Asn Tyr Gly Asn Ala  Asn Gly Ile Ser Asp  Tyr Ile Asn 
        995                 1000                 1005             


Lys Trp  Ile Phe Val Thr Ile  Thr Asn Asp Arg Leu  Gly Asp Ser 
    1010                 1015                 1020             


Lys Leu  Tyr Ile Asn Gly Asn  Leu Ile Asp Gln Lys  Ser Ile Leu 
    1025                 1030                 1035             


Asn Leu  Gly Asn Ile His Val  Ser Asp Asn Ile Leu  Phe Lys Ile 
    1040                 1045                 1050             


Val Asn  Cys Ser Tyr Thr Arg  Tyr Ile Gly Ile Arg  Tyr Phe Asn 
    1055                 1060                 1065             


Ile Phe  Asp Lys Glu Leu Asp  Glu Thr Glu Ile Gln  Thr Leu Tyr 
    1070                 1075                 1080             


Ser Asn  Glu Pro Asn Thr Asn  Ile Leu Lys Asp Phe  Trp Gly Asn 
    1085                 1090                 1095             


Tyr Leu  Leu Tyr Asp Lys Glu  Tyr Tyr Leu Leu Asn  Val Leu Lys 
    1100                 1105                 1110             


Pro Asn  Asn Phe Ile Asp Arg  Arg Lys Asp Ser Thr  Leu Ser Ile 
    1115                 1120                 1125             


Asn Asn  Ile Arg Ser Thr Ile  Leu Leu Ala Asn Arg  Leu Tyr Ser 
    1130                 1135                 1140             


Gly Ile  Lys Val Lys Ile Gln  Arg Val Asn Asn Ser  Ser Thr Asn 
    1145                 1150                 1155             


Asp Asn  Leu Val Arg Lys Asn  Asp Gln Val Tyr Ile  Asn Phe Val 
    1160                 1165                 1170             


Ala Ser  Lys Thr His Leu Phe  Pro Leu Tyr Ala Asp  Thr Ala Thr 
    1175                 1180                 1185             


Thr Asn  Lys Glu Lys Thr Ile  Lys Ile Ser Ser Ser  Gly Asn Arg 
    1190                 1195                 1200             


Phe Asn  Gln Val Val Val Met  Asn Ser Val Gly Asn  Asn Cys Thr 
    1205                 1210                 1215             


Met Asn  Phe Lys Asn Asn Asn  Gly Asn Asn Ile Gly  Leu Leu Gly 
    1220                 1225                 1230             


Phe Lys  Ala Asp Thr Val Val  Ala Ser Thr Trp Tyr  Tyr Thr His 
    1235                 1240                 1245             


Met Arg  Asp His Thr Asn Ser  Asn Gly Cys Phe Trp  Asn Phe Ile 
    1250                 1255                 1260             


Ser Glu  Glu His Gly Trp Gln  Glu Lys 
    1265                 1270         





<210>  13
<211>  3819
<212>  DNA
<213>  Artificial 

<220>
<223>  recombinant protein BONT/E with MDM2 binding motif

<400>  13

atgccgaaaa tcaacagctt caactataac gatccggtga acgatcgtac catcctgtat     60

attaaaccgg gcggttgcca ggaattttac aaaagcttca acatcatgaa aaacatctgg    120

attattccgg aacgtaacgt gattggcacc accccgcagg attttcatcc gccgaccagc    180

ctgaaaaacg gcgatagcag ctattatgat ccgaactatc tgcagtctga tgaagaaaaa    240

gatcgcttcc tgaaaatcgt gaccaaaatc ttcaaccgca tcaacaacaa cctgagcggc    300

ggcattctgc tggaagaact gagcaaagcg aatccgtatc tgggcaacga taacactcca    360

gataaccagt ttcatattgg tgatgcgagc gcggtggaaa ttaaatttag caacggctct    420

caggacattc tgctgccgaa cgtgattatt atgggcgcgg aaccggacct gtttgaaacc    480

aacagcagca acattagcct gcgtaacaac tatatgccga gcaaccatgg ttttggcagc    540

attgcgattg tgacctttag cccggaatat agctttcgct tcaacgataa cagcatgaac    600

gaatttattc aggacccggc gctgaccctg atgcacgagc tgattcatag cctgcatggc    660

ctgtatggcg cgaaaggcat taccaccaaa tataccatca cccagaaaca gaatccgctg    720

attaccaaca ttcgtggcac caacattgaa gaatttctga cctttggcgg caccgatctg    780

aacattatta ccagcgcgca gagcaacgat atctatacca acctgctggc cgattataaa    840

aaaatcgcgt ctaaactgag caaagtgcag gtgagcaatc cgctgctgaa tccgtataaa    900

gatgtgtttg aagcgaaata tggcctggat aaagatgcta gcggcattta tagcgtgaac    960

atcaacaaat tcaacgacat cttcaaaaaa ctgtatagct ttaccgaatt tgatctggcc   1020

accaaatttc aggtgaaatg ccgccagacc tatattggcc agtataaata ttttaaactg   1080

agcaacctgc tgaacgatag catttacaac atcagcgaag gctataacat caacaacctg   1140

aaagtgaact ttcgtggcca gaacgcgaat ttaaatccgc gtattattac cccgattacc   1200

ggccgtggac tagtgaaaaa aattatccgt ttttgcgtgc gtggcattat caccagcctg   1260

acctttgaac ataattgggc acagctggaa aacaaaagcc tggtgccgcg tggcagcaaa   1320

gcgttaaatg atttatgcat cgaaatcaac aacggcgaac tgttttttgt ggcgagcgaa   1380

aacagctata acgatgataa catcaacacc ccgaaagaaa ttgatgatac cgtgaccagc   1440

aataacaact acgaaaacga tctggatcag gtgattctga actttaacag cgaaagcgca   1500

ccgggcctgt ctgatgaaaa actgaacctg accattcaga acgatgcgta tatcccgaaa   1560

tatgatagca acggcaccag cgatattgaa cagcatgatg tgaacgaact gaacgtgttt   1620

ttttatctgg atgcgcagaa agtgccggaa ggcgaaaaca acgtgaatct gaccagctca   1680

attgataccg cgctgctgga acagccgaaa atctatacct tttttagcag cgaattcatc   1740

aacaacgtga acaaaccggt gcaggcggcg ctgtttgtga gctggattca gcaggtgctg   1800

gttgatttta ccaccgaagc gaaccagaaa agcaccgtgg ataaaattgc ggatattagc   1860

attgtggtgc cgtatattgg cctggccctg aacattggca acgaagcgca gaaaggcaac   1920

tttaaagatg cgctggaact gctgggtgcg ggcattctgc tggaatttga accggaactg   1980

ctgattccga ccattctggt gtttaccatc aaaagctttc tgggcagcag cgataacaaa   2040

aacaaagtga tcaaagcgat taacaacgcg ctgaaagaac gtgatgaaaa atggaaagaa   2100

gtgtatagct tcattgtgtc taactggatg accaaaatca acacccagtt caacaaacgt   2160

aaagaacaaa tgtatcaggc gctgcagaac caggtgaacg cgattaaaac catcatcgaa   2220

agcaaataca acagctacac cctggaagaa aaaaacgaac tgaccaacaa atatgacatc   2280

aaacaaatcg aaaatgaact gaaccagaaa gtgagcattg ccatgaacaa cattgatcgc   2340

tttctgaccg aaagcagcat tagctacctg atgaaactga tcaacgaagt gaaaatcaac   2400

aaactgcgcg aatatgatga aaacgtgaaa acctacctgc tgaactatat tattcagcat   2460

ggcagcattc tgggcgaaag ccagcaagaa ctgaacagca tggttaccga taccctgaac   2520

aacagcattc cgtttaaact gagcagctac accgatgata aaatcctgat cagctacttc   2580

aacaaattct tcaaacgcat caaaagcagc agcgtgctga acatgcgtta taaaaacgat   2640

aaatacgtag ataccagcgg ctatgatagc aatatcaaca ttaacggtga tgtgtataaa   2700

tacccgacca acaaaaacca gttcggcatc tacaacgata aactgagcga agtgaacatt   2760

agccagaacg attatatcat ctacgataat aaatataaaa acttcagcat cagcttttgg   2820

gtgcgtattc cgaactacga taacaaaatc gtgaacgtga acaacgaata caccatcatt   2880

aactgcatgc gtgataacaa cagcggctgg aaagtgagcc tgaaccataa cgaaatcatc   2940

tggaccctgc aggataacgc cggcattaac cagaaactgg cctttaacta tggcaacgcg   3000

aacggcatta gcgattacat caacaaatgg atctttgtga ccattaccaa cgatcgtctg   3060

ggcgatagca aactgtatat taacggcaac ctgatcgacc agaaaagcat tctgaacctg   3120

ggcaacattc atgtgagcga taacatcctg ttcaaaattg tgaactgcag ctatacccgt   3180

tatattggca tccgctattt caacatcttc gataaagaac tggatgaaac cgaaattcag   3240

accctgtata gcaacgaacc gaacaccaac atcctgaaag atttctgggg caactatctg   3300

ctgtacgata aagaatatta tctgctgaac gtgctgaaac cgaacaactt tattgatcgc   3360

cgtaaagata gcaccctgag cattaacaac attcgtagca ccattctgct ggccaaccgt   3420

ctgtatagcg gcattaaagt gaaaattcag cgcgtgaaca atagcagcac caacgataac   3480

ctggtgcgta aaaacgatca ggtgtatatc aactttgtgg ccagcaaaac ccacctgttt   3540

ccgctgtatg cggataccgc gaccaccaac aaagaaaaaa ccattaaaat cagcagcagc   3600

ggcaaccgtt ttaaccaggt ggtggtgatg aacagcgtgg gcaacaactg tacaatgaac   3660

ttcaaaaaca acaacggcaa caacattggc ctgctgggct ttaaagcgga taccgtggtg   3720

gcgagcacct ggtattatac ccacatgcgt gatcatacca acagcaacgg ctgcttttgg   3780

aactttatta gcgaagaaca tggctggcag gaaaaatga                          3819



<210>  14
<211>  1272
<212>  PRT
<213>  artificial

<220>
<223>  recombinant protein BONT/E with MDM2 binding motif

<400>  14

Met Pro Lys Ile Asn Ser Phe Asn Tyr Asn Asp Pro Val Asn Asp Arg 
1               5                   10                  15      


Thr Ile Leu Tyr Ile Lys Pro Gly Gly Cys Gln Glu Phe Tyr Lys Ser 
            20                  25                  30          


Phe Asn Ile Met Lys Asn Ile Trp Ile Ile Pro Glu Arg Asn Val Ile 
        35                  40                  45              


Gly Thr Thr Pro Gln Asp Phe His Pro Pro Thr Ser Leu Lys Asn Gly 
    50                  55                  60                  


Asp Ser Ser Tyr Tyr Asp Pro Asn Tyr Leu Gln Ser Asp Glu Glu Lys 
65                  70                  75                  80  


Asp Arg Phe Leu Lys Ile Val Thr Lys Ile Phe Asn Arg Ile Asn Asn 
                85                  90                  95      


Asn Leu Ser Gly Gly Ile Leu Leu Glu Glu Leu Ser Lys Ala Asn Pro 
            100                 105                 110         


Tyr Leu Gly Asn Asp Asn Thr Pro Asp Asn Gln Phe His Ile Gly Asp 
        115                 120                 125             


Ala Ser Ala Val Glu Ile Lys Phe Ser Asn Gly Ser Gln Asp Ile Leu 
    130                 135                 140                 


Leu Pro Asn Val Ile Ile Met Gly Ala Glu Pro Asp Leu Phe Glu Thr 
145                 150                 155                 160 


Asn Ser Ser Asn Ile Ser Leu Arg Asn Asn Tyr Met Pro Ser Asn His 
                165                 170                 175     


Gly Phe Gly Ser Ile Ala Ile Val Thr Phe Ser Pro Glu Tyr Ser Phe 
            180                 185                 190         


Arg Phe Asn Asp Asn Ser Met Asn Glu Phe Ile Gln Asp Pro Ala Leu 
        195                 200                 205             


Thr Leu Met His Glu Leu Ile His Ser Leu His Gly Leu Tyr Gly Ala 
    210                 215                 220                 


Lys Gly Ile Thr Thr Lys Tyr Thr Ile Thr Gln Lys Gln Asn Pro Leu 
225                 230                 235                 240 


Ile Thr Asn Ile Arg Gly Thr Asn Ile Glu Glu Phe Leu Thr Phe Gly 
                245                 250                 255     


Gly Thr Asp Leu Asn Ile Ile Thr Ser Ala Gln Ser Asn Asp Ile Tyr 
            260                 265                 270         


Thr Asn Leu Leu Ala Asp Tyr Lys Lys Ile Ala Ser Lys Leu Ser Lys 
        275                 280                 285             


Val Gln Val Ser Asn Pro Leu Leu Asn Pro Tyr Lys Asp Val Phe Glu 
    290                 295                 300                 


Ala Lys Tyr Gly Leu Asp Lys Asp Ala Ser Gly Ile Tyr Ser Val Asn 
305                 310                 315                 320 


Ile Asn Lys Phe Asn Asp Ile Phe Lys Lys Leu Tyr Ser Phe Thr Glu 
                325                 330                 335     


Phe Asp Leu Ala Thr Lys Phe Gln Val Lys Cys Arg Gln Thr Tyr Ile 
            340                 345                 350         


Gly Gln Tyr Lys Tyr Phe Lys Leu Ser Asn Leu Leu Asn Asp Ser Ile 
        355                 360                 365             


Tyr Asn Ile Ser Glu Gly Tyr Asn Ile Asn Asn Leu Lys Val Asn Phe 
    370                 375                 380                 


Arg Gly Gln Asn Ala Asn Leu Asn Pro Arg Ile Ile Thr Pro Ile Thr 
385                 390                 395                 400 


Gly Arg Gly Leu Val Lys Lys Ile Ile Arg Phe Cys Val Arg Gly Ile 
                405                 410                 415     


Ile Thr Ser Leu Thr Phe Glu His Asn Trp Ala Gln Leu Glu Asn Lys 
            420                 425                 430         


Ser Leu Val Pro Arg Gly Ser Lys Ala Leu Asn Asp Leu Cys Ile Glu 
        435                 440                 445             


Ile Asn Asn Gly Glu Leu Phe Phe Val Ala Ser Glu Asn Ser Tyr Asn 
    450                 455                 460                 


Asp Asp Asn Ile Asn Thr Pro Lys Glu Ile Asp Asp Thr Val Thr Ser 
465                 470                 475                 480 


Asn Asn Asn Tyr Glu Asn Asp Leu Asp Gln Val Ile Leu Asn Phe Asn 
                485                 490                 495     


Ser Glu Ser Ala Pro Gly Leu Ser Asp Glu Lys Leu Asn Leu Thr Ile 
            500                 505                 510         


Gln Asn Asp Ala Tyr Ile Pro Lys Tyr Asp Ser Asn Gly Thr Ser Asp 
        515                 520                 525             


Ile Glu Gln His Asp Val Asn Glu Leu Asn Val Phe Phe Tyr Leu Asp 
    530                 535                 540                 


Ala Gln Lys Val Pro Glu Gly Glu Asn Asn Val Asn Leu Thr Ser Ser 
545                 550                 555                 560 


Ile Asp Thr Ala Leu Leu Glu Gln Pro Lys Ile Tyr Thr Phe Phe Ser 
                565                 570                 575     


Ser Glu Phe Ile Asn Asn Val Asn Lys Pro Val Gln Ala Ala Leu Phe 
            580                 585                 590         


Val Ser Trp Ile Gln Gln Val Leu Val Asp Phe Thr Thr Glu Ala Asn 
        595                 600                 605             


Gln Lys Ser Thr Val Asp Lys Ile Ala Asp Ile Ser Ile Val Val Pro 
    610                 615                 620                 


Tyr Ile Gly Leu Ala Leu Asn Ile Gly Asn Glu Ala Gln Lys Gly Asn 
625                 630                 635                 640 


Phe Lys Asp Ala Leu Glu Leu Leu Gly Ala Gly Ile Leu Leu Glu Phe 
                645                 650                 655     


Glu Pro Glu Leu Leu Ile Pro Thr Ile Leu Val Phe Thr Ile Lys Ser 
            660                 665                 670         


Phe Leu Gly Ser Ser Asp Asn Lys Asn Lys Val Ile Lys Ala Ile Asn 
        675                 680                 685             


Asn Ala Leu Lys Glu Arg Asp Glu Lys Trp Lys Glu Val Tyr Ser Phe 
    690                 695                 700                 


Ile Val Ser Asn Trp Met Thr Lys Ile Asn Thr Gln Phe Asn Lys Arg 
705                 710                 715                 720 


Lys Glu Gln Met Tyr Gln Ala Leu Gln Asn Gln Val Asn Ala Ile Lys 
                725                 730                 735     


Thr Ile Ile Glu Ser Lys Tyr Asn Ser Tyr Thr Leu Glu Glu Lys Asn 
            740                 745                 750         


Glu Leu Thr Asn Lys Tyr Asp Ile Lys Gln Ile Glu Asn Glu Leu Asn 
        755                 760                 765             


Gln Lys Val Ser Ile Ala Met Asn Asn Ile Asp Arg Phe Leu Thr Glu 
    770                 775                 780                 


Ser Ser Ile Ser Tyr Leu Met Lys Leu Ile Asn Glu Val Lys Ile Asn 
785                 790                 795                 800 


Lys Leu Arg Glu Tyr Asp Glu Asn Val Lys Thr Tyr Leu Leu Asn Tyr 
                805                 810                 815     


Ile Ile Gln His Gly Ser Ile Leu Gly Glu Ser Gln Gln Glu Leu Asn 
            820                 825                 830         


Ser Met Val Thr Asp Thr Leu Asn Asn Ser Ile Pro Phe Lys Leu Ser 
        835                 840                 845             


Ser Tyr Thr Asp Asp Lys Ile Leu Ile Ser Tyr Phe Asn Lys Phe Phe 
    850                 855                 860                 


Lys Arg Ile Lys Ser Ser Ser Val Leu Asn Met Arg Tyr Lys Asn Asp 
865                 870                 875                 880 


Lys Tyr Val Asp Thr Ser Gly Tyr Asp Ser Asn Ile Asn Ile Asn Gly 
                885                 890                 895     


Asp Val Tyr Lys Tyr Pro Thr Asn Lys Asn Gln Phe Gly Ile Tyr Asn 
            900                 905                 910         


Asp Lys Leu Ser Glu Val Asn Ile Ser Gln Asn Asp Tyr Ile Ile Tyr 
        915                 920                 925             


Asp Asn Lys Tyr Lys Asn Phe Ser Ile Ser Phe Trp Val Arg Ile Pro 
    930                 935                 940                 


Asn Tyr Asp Asn Lys Ile Val Asn Val Asn Asn Glu Tyr Thr Ile Ile 
945                 950                 955                 960 


Asn Cys Met Arg Asp Asn Asn Ser Gly Trp Lys Val Ser Leu Asn His 
                965                 970                 975     


Asn Glu Ile Ile Trp Thr Leu Gln Asp Asn Ala Gly Ile Asn Gln Lys 
            980                 985                 990         


Leu Ala Phe Asn Tyr Gly Asn Ala  Asn Gly Ile Ser Asp  Tyr Ile Asn 
        995                 1000                 1005             


Lys Trp  Ile Phe Val Thr Ile  Thr Asn Asp Arg Leu  Gly Asp Ser 
    1010                 1015                 1020             


Lys Leu  Tyr Ile Asn Gly Asn  Leu Ile Asp Gln Lys  Ser Ile Leu 
    1025                 1030                 1035             


Asn Leu  Gly Asn Ile His Val  Ser Asp Asn Ile Leu  Phe Lys Ile 
    1040                 1045                 1050             


Val Asn  Cys Ser Tyr Thr Arg  Tyr Ile Gly Ile Arg  Tyr Phe Asn 
    1055                 1060                 1065             


Ile Phe  Asp Lys Glu Leu Asp  Glu Thr Glu Ile Gln  Thr Leu Tyr 
    1070                 1075                 1080             


Ser Asn  Glu Pro Asn Thr Asn  Ile Leu Lys Asp Phe  Trp Gly Asn 
    1085                 1090                 1095             


Tyr Leu  Leu Tyr Asp Lys Glu  Tyr Tyr Leu Leu Asn  Val Leu Lys 
    1100                 1105                 1110             


Pro Asn  Asn Phe Ile Asp Arg  Arg Lys Asp Ser Thr  Leu Ser Ile 
    1115                 1120                 1125             


Asn Asn  Ile Arg Ser Thr Ile  Leu Leu Ala Asn Arg  Leu Tyr Ser 
    1130                 1135                 1140             


Gly Ile  Lys Val Lys Ile Gln  Arg Val Asn Asn Ser  Ser Thr Asn 
    1145                 1150                 1155             


Asp Asn  Leu Val Arg Lys Asn  Asp Gln Val Tyr Ile  Asn Phe Val 
    1160                 1165                 1170             


Ala Ser  Lys Thr His Leu Phe  Pro Leu Tyr Ala Asp  Thr Ala Thr 
    1175                 1180                 1185             


Thr Asn  Lys Glu Lys Thr Ile  Lys Ile Ser Ser Ser  Gly Asn Arg 
    1190                 1195                 1200             


Phe Asn  Gln Val Val Val Met  Asn Ser Val Gly Asn  Asn Cys Thr 
    1205                 1210                 1215             


Met Asn  Phe Lys Asn Asn Asn  Gly Asn Asn Ile Gly  Leu Leu Gly 
    1220                 1225                 1230             


Phe Lys  Ala Asp Thr Val Val  Ala Ser Thr Trp Tyr  Tyr Thr His 
    1235                 1240                 1245             


Met Arg  Asp His Thr Asn Ser  Asn Gly Cys Phe Trp  Asn Phe Ile 
    1250                 1255                 1260             


Ser Glu  Glu His Gly Trp Gln  Glu Lys 
    1265                 1270         



<210>  15
<211>  12
<212>  PRT
<213>  Mus musculus

<400>  15

Thr Leu Ser Ser Gln His Asn Thr Tyr Thr Ile Glu 
1               5                   10          


<210>  16
<211>  7
<212>  PRT
<213>  Mus musculus

<400>  16

Lys Asp Gly Ser His Ser Thr 
1               5           


<210>  17
<211>  13
<212>  PRT
<213>  Mus musculus

<400>  17

Gly Val Gly Asp Thr Ile Lys Glu Gln Phe Val Tyr Val 
1               5                   10              


<210>  18
<211>  10
<212>  PRT
<213>  Mus musculus

<400>  18

Gly Tyr Thr Phe Asn Thr Tyr Ala Val Asn 
1               5                   10  


<210>  19
<211>  19
<212>  PRT
<213>  Mus musculus

<400>  19

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


Val Lys Asp 
            


<210>  20
<211>  10
<212>  PRT
<213>  Mus musculus

<400>  20

Gly Asn Gly Asn Tyr Val Ser Phe Ala Tyr 
1               5                   10  


<210>  21
<211>  115
<212>  PRT
<213>  Mus musculus

<400>  21

Gln Leu Val Leu Thr Gln Ser Ser Ser Ala Ser Phe Ser Leu Gly Ala 
1               5                   10                  15      


Ser Ala Lys Leu Thr Cys Thr Leu Ser Ser Gln His Asn Thr Tyr Thr 
            20                  25                  30          


Ile Glu Trp Tyr Gln Gln Gln Pro Leu Lys Pro Pro Lys Tyr Val Met 
        35                  40                  45              


Glu Leu Lys Lys Asp Gly Ser His Ser Thr Gly Asp Gly Ile Pro Asp 
    50                  55                  60                  


Arg Phe Ser Gly Ser Ser Ser Gly Ala Asp Arg Tyr Leu Ser Ile Ser 
65                  70                  75                  80  


Asn Ile Gln Pro Glu Asp Glu Ala Ile Tyr Ile Cys Gly Val Gly Asp 
                85                  90                  95      


Thr Ile Lys Glu Gln Phe Val Tyr Val Phe Gly Gly Gly Thr Lys Val 
            100                 105                 110         


Thr Val Leu 
        115 


<210>  22
<211>  121
<212>  PRT
<213>  Mus musculus

<400>  22

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


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


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


Ala Arg Ile Arg Ser Lys Ser Tyr Asn Tyr Val Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Gln Ser Met 
65                  70                  75                  80  


Leu Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Met Tyr 
                85                  90                  95      


Tyr Cys Val Lys Gly Asn Gly Asn Tyr Val Ser Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ala 
        115                 120     






