                         SEQUENCE LISTING

<110>  Matthiessen, et al.
 
<120>  Recombinant VWF Formulations

<130>  31315/43550

<150>  61/017,881
<151>  2007-12-31

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  8833
<212>  DNA
<213>  Artificial Sequence       

<220>
<223>  Synthetic Polynucleotide


<220>
<221>  misc_feature
<223>  prepro-vWF

<400>  1
agctcacagc tattgtggtg ggaaagggag ggtggttggt ggatgtcaca gcttgggctt       60

tatctccccc agcagtgggg actccacagc ccctgggcta cataacagca agacagtccg      120

gagctgtagc agacctgatt gagcctttgc agcagctgag agcatggcct agggtgggcg      180

gcaccattgt ccagcagctg agtttcccag ggaccttgga gatagccgca gccctcattt      240

gcaggggaag atgattcctg ccagatttgc cggggtgctg cttgctctgg ccctcatttt      300

gccagggacc ctttgtgcag aaggaactcg cggcaggtca tccacggccc gatgcagcct      360

tttcggaagt gacttcgtca acacctttga tgggagcatg tacagctttg cgggatactg      420

cagttacctc ctggcagggg gctgccagaa acgctccttc tcgattattg gggacttcca      480

gaatggcaag agagtgagcc tctccgtgta tcttggggaa ttttttgaca tccatttgtt      540

tgtcaatggt accgtgacac agggggacca aagagtctcc atgccctatg cctccaaagg      600

gctgtatcta gaaactgagg ctgggtacta caagctgtcc ggtgaggcct atggctttgt      660

ggccaggatc gatggcagcg gcaactttca agtcctgctg tcagacagat acttcaacaa      720

gacctgcggg ctgtgtggca actttaacat ctttgctgaa gatgacttta tgacccaaga      780

agggaccttg acctcggacc cttatgactt tgccaactca tgggctctga gcagtggaga      840

acagtggtgt gaacgggcat ctcctcccag cagctcatgc aacatctcct ctggggaaat      900

gcagaagggc ctgtgggagc agtgccagct tctgaagagc acctcggtgt ttgcccgctg      960

ccaccctctg gtggaccccg agccttttgt ggccctgtgt gagaagactt tgtgtgagtg     1020

tgctgggggg ctggagtgcg cctgccctgc cctcctggag tacgcccgga cctgtgccca     1080

ggagggaatg gtgctgtacg gctggaccga ccacagcgcg tgcagcccag tgtgccctgc     1140

tggtatggag tataggcagt gtgtgtcccc ttgcgccagg acctgccaga gcctgcacat     1200

caatgaaatg tgtcaggagc gatgcgtgga tggctgcagc tgccctgagg gacagctcct     1260

ggatgaaggc ctctgcgtgg agagcaccga gtgtccctgc gtgcattccg gaaagcgcta     1320

ccctcccggc acctccctct ctcgagactg caacacctgc atttgccgaa acagccagtg     1380

gatctgcagc aatgaagaat gtccagggga gtgccttgtc acaggtcaat cacacttcaa     1440

gagctttgac aacagatact tcaccttcag tgggatctgc cagtacctgc tggcccggga     1500

ttgccaggac cactccttct ccattgtcat tgagactgtc cagtgtgctg atgaccgcga     1560

cgctgtgtgc acccgctccg tcaccgtccg gctgcctggc ctgcacaaca gccttgtgaa     1620

actgaagcat ggggcaggag ttgccatgga tggccaggac gtccagctcc ccctcctgaa     1680

aggtgacctc cgcatccagc atacagtgac ggcctccgtg cgcctcagct acggggagga     1740

cctgcagatg gactgggatg gccgcgggag gctgctggtg aagctgtccc ccgtctatgc     1800

cgggaagacc tgcggcctgt gtgggaatta caatggcaac cagggcgacg acttccttac     1860

cccctctggg ctggcggagc cccgggtgga ggacttcggg aacgcctgga agctgcacgg     1920

ggactgccag gacctgcaga agcagcacag cgatccctgc gccctcaacc cgcgcatgac     1980

caggttctcc gaggaggcgt gcgcggtcct gacgtccccc acattcgagg cctgccatcg     2040

tgccgtcagc ccgctgccct acctgcggaa ctgccgctac gacgtgtgct cctgctcgga     2100

cggccgcgag tgcctgtgcg gcgccctggc cagctatgcc gcggcctgcg cggggagagg     2160

cgtgcgcgtc gcgtggcgcg agccaggccg ctgtgagctg aactgcccga aaggccaggt     2220

gtacctgcag tgcgggaccc cctgcaacct gacctgccgc tctctctctt acccggatga     2280

ggaatgcaat gaggcctgcc tggagggctg cttctgcccc ccagggctct acatggatga     2340

gaggggggac tgcgtgccca aggcccagtg cccctgttac tatgacggtg agatcttcca     2400

gccagaagac atcttctcag accatcacac catgtgctac tgtgaggatg gcttcatgca     2460

ctgtaccatg agtggagtcc ccggaagctt gctgcctgac gctgtcctca gcagtcccct     2520

gtctcatcgc agcaaaagga gcctatcctg tcggcccccc atggtcaagc tggtgtgtcc     2580

cgctgacaac ctgcgggctg aagggctcga gtgtaccaaa acgtgccaga actatgacct     2640

ggagtgcatg agcatgggct gtgtctctgg ctgcctctgc cccccgggca tggtccggca     2700

tgagaacaga tgtgtggccc tggaaaggtg tccctgcttc catcagggca aggagtatgc     2760

ccctggagaa acagtgaaga ttggctgcaa cacttgtgtc tgtcgggacc ggaagtggaa     2820

ctgcacagac catgtgtgtg atgccacgtg ctccacgatc ggcatggccc actacctcac     2880

cttcgacggg ctcaaatacc tgttccccgg ggagtgccag tacgttctgg tgcaggatta     2940

ctgcggcagt aaccctggga cctttcggat cctagtgggg aataagggat gcagccaccc     3000

ctcagtgaaa tgcaagaaac gggtcaccat cctggtggag ggaggagaga ttgagctgtt     3060

tgacggggag gtgaatgtga agaggcccat gaaggatgag actcactttg aggtggtgga     3120

gtctggccgg tacatcattc tgctgctggg caaagccctc tccgtggtct gggaccgcca     3180

cctgagcatc tccgtggtcc tgaagcagac ataccaggag aaagtgtgtg gcctgtgtgg     3240

gaattttgat ggcatccaga acaatgacct caccagcagc aacctccaag tggaggaaga     3300

ccctgtggac tttgggaact cctggaaagt gagctcgcag tgtgctgaca ccagaaaagt     3360

gcctctggac tcatcccctg ccacctgcca taacaacatc atgaagcaga cgatggtgga     3420

ttcctcctgt agaatcctta ccagtgacgt cttccaggac tgcaacaagc tggtggaccc     3480

cgagccatat ctggatgtct gcatttacga cacctgctcc tgtgagtcca ttggggactg     3540

cgcctgcttc tgcgacacca ttgctgccta tgcccacgtg tgtgcccagc atggcaaggt     3600

ggtgacctgg aggacggcca cattgtgccc ccagagctgc gaggagagga atctccggga     3660

gaacgggtat gagtgtgagt ggcgctataa cagctgtgca cctgcctgtc aagtcacgtg     3720

tcagcaccct gagccactgg cctgccctgt gcagtgtgtg gagggctgcc atgcccactg     3780

ccctccaggg aaaatcctgg atgagctttt gcagacctgc gttgaccctg aagactgtcc     3840

agtgtgtgag gtggctggcc ggcgttttgc ctcaggaaag aaagtcacct tgaatcccag     3900

tgaccctgag cactgccaga tttgccactg tgatgttgtc aacctcacct gtgaagcctg     3960

ccaggagccg ggaggcctgg tggtgcctcc cacagatgcc ccggtgagcc ccaccactct     4020

gtatgtggag gacatctcgg aaccgccgtt gcacgatttc tactgcagca ggctactgga     4080

cctggtcttc ctgctggatg gctcctccag gctgtccgag gctgagtttg aagtgctgaa     4140

ggcctttgtg gtggacatga tggagcggct gcgcatctcc cagaagtggg tccgcgtggc     4200

cgtggtggag taccacgacg gctcccacgc ctacatcggg ctcaaggacc ggaagcgacc     4260

gtcagagctg cggcgcattg ccagccaggt gaagtatgcg ggcagccagg tggcctccac     4320

cagcgaggtc ttgaaataca cactgttcca aatcttcagc aagatcgacc gccctgaagc     4380

ctcccgcatc accctgctcc tgatggccag ccaggagccc caacggatgt cccggaactt     4440

tgtccgctac gtccagggcc tgaagaagaa gaaggtcatt gtgatcccgg tgggcattgg     4500

gccccatgcc aacctcaagc agatccgcct catcgagaag caggcccctg agaacaaggc     4560

cttcgtgctg agcagtgtgg atgagctgga gcagcaaagg gacgagatcg ttagctacct     4620

ctgtgacctt gcccctgaag cccctcctcc tactctgccc cccgacatgg cacaagtcac     4680

tgtgggcccg gggctcttgg gggtttcgac cctggggccc aagaggaact ccatggttct     4740

ggatgtggcg ttcgtcctgg aaggatcgga caaaattggt gaagccgact tcaacaggag     4800

caaggagttc atggaggagg tgattcagcg gatggatgtg ggccaggaca gcatccacgt     4860

cacggtgctg cagtactcct acatggtgac tgtggagtac cccttcagcg aggcacagtc     4920

caaaggggac atcctgcagc gggtgcgaga gatccgctac cagggcggca acaggaccaa     4980

cactgggctg gccctgcggt acctctctga ccacagcttc ttggtcagcc agggtgaccg     5040

ggagcaggcg cccaacctgg tctacatggt caccggaaat cctgcctctg atgagatcaa     5100

gaggctgcct ggagacatcc aggtggtgcc cattggagtg ggccctaatg ccaacgtgca     5160

ggagctggag aggattggct ggcccaatgc ccctatcctc atccaggact ttgagacgct     5220

cccccgagag gctcctgacc tggtgctgca gaggtgctgc tccggagagg ggctgcagat     5280

ccccaccctc tcccctgcac ctgactgcag ccagcccctg gacgtgatcc ttctcctgga     5340

tggctcctcc agtttcccag cttcttattt tgatgaaatg aagagtttcg ccaaggcttt     5400

catttcaaaa gccaatatag ggcctcgtct cactcaggtg tcagtgctgc agtatggaag     5460

catcaccacc attgacgtgc catggaacgt ggtcccggag aaagcccatt tgctgagcct     5520

tgtggacgtc atgcagcggg agggaggccc cagccaaatc ggggatgcct tgggctttgc     5580

tgtgcgatac ttgacttcag aaatgcatgg tgccaggccg ggagcctcaa aggcggtggt     5640

catcctggtc acggacgtct ctgtggattc agtggatgca gcagctgatg ccgccaggtc     5700

caacagagtg acagtgttcc ctattggaat tggagatcgc tacgatgcag cccagctacg     5760

gatcttggca ggcccagcag gcgactccaa cgtggtgaag ctccagcgaa tcgaagacct     5820

ccctaccatg gtcaccttgg gcaattcctt cctccacaaa ctgtgctctg gatttgttag     5880

gatttgcatg gatgaggatg ggaatgagaa gaggcccggg gacgtctgga ccttgccaga     5940

ccagtgccac accgtgactt gccagccaga tggccagacc ttgctgaaga gtcatcgggt     6000

caactgtgac cgggggctga ggccttcgtg ccctaacagc cagtcccctg ttaaagtgga     6060

agagacctgt ggctgccgct ggacctgccc ctgcgtgtgc acaggcagct ccactcggca     6120

catcgtgacc tttgatgggc agaatttcaa gctgactggc agctgttctt atgtcctatt     6180

tcaaaacaag gagcaggacc tggaggtgat tctccataat ggtgcctgca gccctggagc     6240

aaggcagggc tgcatgaaat ccatcgaggt gaagcacagt gccctctccg tcgagctgca     6300

cagtgacatg gaggtgacgg tgaatgggag actggtctct gttccttacg tgggtgggaa     6360

catggaagtc aacgtttatg gtgccatcat gcatgaggtc agattcaatc accttggtca     6420

catcttcaca ttcactccac aaaacaatga gttccaactg cagctcagcc ccaagacttt     6480

tgcttcaaag acgtatggtc tgtgtgggat ctgtgatgag aacggagcca atgacttcat     6540

gctgagggat ggcacagtca ccacagactg gaaaacactt gttcaggaat ggactgtgca     6600

gcggccaggg cagacgtgcc agcccatcct ggaggagcag tgtcttgtcc ccgacagctc     6660

ccactgccag gtcctcctct taccactgtt tgctgaatgc cacaaggtcc tggctccagc     6720

cacattctat gccatctgcc agcaggacag ttgccaccag gagcaagtgt gtgaggtgat     6780

cgcctcttat gcccacctct gtcggaccaa cggggtctgc gttgactgga ggacacctga     6840

tttctgtgct atgtcatgcc caccatctct ggtctacaac cactgtgagc atggctgtcc     6900

ccggcactgt gatggcaacg tgagctcctg tggggaccat ccctccgaag gctgtttctg     6960

ccctccagat aaagtcatgt tggaaggcag ctgtgtccct gaagaggcct gcactcagtg     7020

cattggtgag gatggagtcc agcaccagtt cctggaagcc tgggtcccgg accaccagcc     7080

ctgtcagatc tgcacatgcc tcagcgggcg gaaggtcaac tgcacaacgc agccctgccc     7140

cacggccaaa gctcccacgt gtggcctgtg tgaagtagcc cgcctccgcc agaatgcaga     7200

ccagtgctgc cccgagtatg agtgtgtgtg tgacccagtg agctgtgacc tgcccccagt     7260

gcctcactgt gaacgtggcc tccagcccac actgaccaac cctggcgagt gcagacccaa     7320

cttcacctgc gcctgcagga aggaggagtg caaaagagtg tccccaccct cctgcccccc     7380

gcaccgtttg cccacccttc ggaagaccca gtgctgtgat gagtatgagt gtgcctgcaa     7440

ctgtgtcaac tccacagtga gctgtcccct tgggtacttg gcctcaactg ccaccaatga     7500

ctgtggctgt accacaacca cctgccttcc cgacaaggtg tgtgtccacc gaagcaccat     7560

ctaccctgtg ggccagttct gggaggaggg ctgcgatgtg tgcacctgca ccgacatgga     7620

ggatgccgtg atgggcctcc gcgtggccca gtgctcccag aagccctgtg aggacagctg     7680

tcggtcgggc ttcacttacg ttctgcatga aggcgagtgc tgtggaaggt gcctgccatc     7740

tgcctgtgag gtggtgactg gctcaccgcg gggggactcc cagtcttcct ggaagagtgt     7800

cggctcccag tgggcctccc cggagaaccc ctgcctcatc aatgagtgtg tccgagtgaa     7860

ggaggaggtc tttatacaac aaaggaacgt ctcctgcccc cagctggagg tccctgtctg     7920

cccctcgggc tttcagctga gctgtaagac ctcagcgtgc tgcccaagct gtcgctgtga     7980

gcgcatggag gcctgcatgc tcaatggcac tgtcattggg cccgggaaga ctgtgatgat     8040

cgatgtgtgc acgacctgcc gctgcatggt gcaggtgggg gtcatctctg gattcaagct     8100

ggagtgcagg aagaccacct gcaacccctg ccccctgggt tacaaggaag aaaataacac     8160

aggtgaatgt tgtgggagat gtttgcctac ggcttgcacc attcagctaa gaggaggaca     8220

gatcatgaca ctgaagcgtg atgagacgct ccaggatggc tgtgatactc acttctgcaa     8280

ggtcaatgag agaggagagt acttctggga gaagagggtc acaggctgcc caccctttga     8340

tgaacacaag tgtctggctg agggaggtaa aattatgaaa attccaggca cctgctgtga     8400

cacatgtgag gagcctgagt gcaacgacat cactgccagg ctgcagtatg tcaaggtggg     8460

aagctgtaag tctgaagtag aggtggatat ccactactgc cagggcaaat gtgccagcaa     8520

agccatgtac tccattgaca tcaacgatgt gcaggaccag tgctcctgct gctctccgac     8580

acggacggag cccatgcagg tggccctgca ctgcaccaat ggctctgttg tgtaccatga     8640

ggttctcaat gccatggagt gcaaatgctc ccccaggaag tgcagcaagt gaggctgctg     8700

cagctgcatg ggtgcctgct gctgcctgcc ttggcctgat ggccaggcca gagtgctgcc     8760

agtcctctgc atgttctgct cttgtgccct tctgagccca caataaaggc tgagctctta     8820

tcttgcaaaa ggc                                                        8833


<210>  2
<211>  2783
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide


<220>
<221>  MISC_FEATURE
<223>  prepro-vWF

<400>  2

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


Thr Leu Cys Ala Glu Gly Thr Arg Gly Arg Ser Ser Thr Ala Arg Cys 
            20                  25                  30          


Ser Leu Phe Gly Ser Asp Phe Val Asn Thr Phe Asp Gly Ser Met Tyr 
        35                  40                  45              


Ser Phe Ala Gly Tyr Cys Ser Tyr Leu Leu Ala Gly Gly Cys Gln Lys 
    50                  55                  60                  


Arg Ser Phe Ser Ile Ile Gly Asp Phe Gln Asn Gly Lys Arg Val Ser 
65                  70                  75                  80  


Leu Ser Val Tyr Leu Gly Glu Phe Phe Asp Ile His Leu Phe Val Asn 
                85                  90                  95      


Gly Thr Val Thr Gln Gly Asp Gln Arg Val Ser Met Pro Tyr Ala Ser 
            100                 105                 110         


Lys Leu Glu Thr Glu Ala Gly Tyr Tyr Lys Leu Ser Gly Glu Ala Tyr 
        115                 120                 125             


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


Ser Asp Arg Tyr Phe Asn Lys Thr Cys Gly Leu Cys Gly Asn Phe Asn 
145                 150                 155                 160 


Ile Phe Ala Glu Asp Asp Phe Met Thr Gln Glu Gly Thr Leu Thr Ser 
                165                 170                 175     


Asp Pro Tyr Asp Phe Ala Asn Ser Trp Ala Leu Ser Ser Gly Glu Gln 
            180                 185                 190         


Trp Cys Glu Arg Pro Ser Ser Ser Cys Asn Ile Ser Ser Gly Glu Met 
        195                 200                 205             


Gln Lys Gly Leu Trp Glu Gln Cys Gln Leu Leu Lys Ser Thr Ser Val 
    210                 215                 220                 


Phe Ala Arg Cys His Pro Leu Val Asp Pro Glu Pro Phe Cys Glu Lys 
225                 230                 235                 240 


Thr Leu Cys Glu Cys Ala Gly Gly Leu Glu Cys Ala Cys Pro Ala Leu 
                245                 250                 255     


Leu Glu Tyr Ala Arg Thr Cys Ala Gln Glu Gly Met Val Leu Tyr Gly 
            260                 265                 270         


Trp Thr Asp His Ser Ala Cys Ser Pro Val Cys Pro Ala Gly Met Glu 
        275                 280                 285             


Tyr Arg Gln Cys Val Ser Pro Cys Ala Arg Thr Cys Gln Ser Leu His 
    290                 295                 300                 


Ile Asn Glu Met Cys Gln Glu Arg Cys Val Asp Gly Cys Ser Cys Pro 
305                 310                 315                 320 


Glu Gly Gln Leu Leu Asp Glu Gly Leu Cys Val Glu Ser Thr Glu Cys 
                325                 330                 335     


Pro Cys Val His Ser Gly Lys Arg Tyr Pro Pro Gly Thr Ser Leu Ser 
            340                 345                 350         


Arg Asp Cys Asn Thr Cys Ile Cys Arg Asn Ser Gln Trp Ile Cys Ser 
        355                 360                 365             


Asn Glu Glu Cys Pro Gly Glu Cys Leu Val Thr Gly Gln Ser His Phe 
    370                 375                 380                 


Lys Ser Phe Asp Asn Arg Tyr Phe Thr Phe Ser Gly Ile Cys Gln Tyr 
385                 390                 395                 400 


Leu Leu Ala Arg Asp Cys Gln Asp His Ser Phe Ser Ile Val Ile Glu 
                405                 410                 415     


Thr Val Gln Cys Ala Asp Asp Arg Asp Ala Val Cys Thr Arg Ser Val 
            420                 425                 430         


Thr Val Arg Leu Pro Gly Leu His Asn Ser Leu Val Lys Leu Lys His 
        435                 440                 445             


Gly Ala Gly Val Ala Met Asp Gly Gln Asp Val Gln Leu Pro Leu Leu 
    450                 455                 460                 


Lys Gly Asp Leu Arg Ile Gln His Thr Val Thr Ala Ser Val Arg Leu 
465                 470                 475                 480 


Ser Tyr Gly Glu Asp Leu Gln Met Asp Trp Asp Gly Arg Gly Arg Leu 
                485                 490                 495     


Leu Val Lys Leu Ser Pro Val Tyr Ala Gly Lys Thr Cys Gly Leu Cys 
            500                 505                 510         


Gly Asn Tyr Asn Gly Asn Gln Gly Asp Asp Phe Leu Thr Pro Ser Gly 
        515                 520                 525             


Leu Ala Glu Pro Arg Val Glu Asp Phe Gly Asn Ala Trp Lys Leu His 
    530                 535                 540                 


Gly Asp Cys Gln Asp Leu Gln Lys Gln His Ser Asp Pro Cys Ala Leu 
545                 550                 555                 560 


Asn Pro Arg Met Thr Arg Phe Ser Glu Glu Ala Cys Ala Val Leu Thr 
                565                 570                 575     


Ser Pro Thr Phe Glu Ala Cys His Arg Ala Val Ser Pro Leu Pro Tyr 
            580                 585                 590         


Leu Arg Asn Cys Arg Tyr Asp Val Cys Ser Cys Ser Asp Gly Arg Glu 
        595                 600                 605             


Cys Leu Cys Gly Ser Tyr Ala Ala Ala Cys Ala Gly Arg Gly Val Arg 
    610                 615                 620                 


Val Ala Trp Arg Glu Pro Gly Arg Cys Glu Leu Asn Cys Pro Lys Gly 
625                 630                 635                 640 


Gln Val Tyr Leu Gln Cys Gly Thr Pro Cys Asn Leu Thr Cys Arg Ser 
                645                 650                 655     


Leu Ser Tyr Pro Asp Glu Glu Cys Asn Glu Ala Cys Leu Glu Gly Cys 
            660                 665                 670         


Phe Cys Pro Pro Met Asp Glu Arg Gly Asp Cys Val Pro Lys Ala Gln 
        675                 680                 685             


Cys Pro Cys Tyr Tyr Asp Gly Glu Ile Phe Gln Pro Glu Asp Ile Phe 
    690                 695                 700                 


Ser Asp His His Thr Met Cys Tyr Cys Glu Asp Gly Phe Met His Cys 
705                 710                 715                 720 


Thr Met Ser Gly Val Pro Gly Ser Leu Leu Pro Asp Ala Val Leu Ser 
                725                 730                 735     


Ser Pro Leu Ser His Arg Ser Lys Arg Ser Leu Ser Cys Arg Pro Pro 
            740                 745                 750         


Met Val Lys Leu Val Cys Pro Ala Asp Asn Leu Arg Ala Glu Gly Leu 
        755                 760                 765             


Glu Cys Thr Lys Thr Cys Gln Asn Tyr Asp Leu Glu Cys Met Ser Met 
    770                 775                 780                 


Gly Cys Val Ser Gly Cys Leu Cys Pro Pro Gly Met Val Arg His Glu 
785                 790                 795                 800 


Asn Arg Cys Glu Arg Cys Pro Cys Phe His Gln Gly Lys Glu Tyr Ala 
                805                 810                 815     


Pro Gly Glu Thr Val Lys Ile Gly Cys Asn Thr Cys Val Cys Arg Asp 
            820                 825                 830         


Arg Lys Trp Asn Cys Thr Asp His Val Cys Asp Ala Thr Cys Ser Thr 
        835                 840                 845             


Ile Gly Met Ala His Tyr Leu Thr Phe Asp Gly Leu Lys Tyr Leu Phe 
    850                 855                 860                 


Pro Gly Glu Cys Gln Tyr Val Leu Val Gln Asp Tyr Cys Gly Ser Asn 
865                 870                 875                 880 


Pro Gly Thr Phe Arg Ile Leu Val Gly Asn Lys Gly Cys Ser His Pro 
                885                 890                 895     


Ser Val Lys Cys Lys Lys Arg Val Thr Ile Leu Val Glu Gly Gly Glu 
            900                 905                 910         


Ile Glu Leu Phe Asp Gly Glu Val Asn Val Lys Arg Pro Met Lys Asp 
        915                 920                 925             


Glu Thr His Phe Glu Val Val Glu Ser Gly Arg Tyr Ile Ile Leu Leu 
    930                 935                 940                 


Leu Gly Lys Ala Leu Ser Val Val Trp Asp Arg His Leu Ser Ile Ser 
945                 950                 955                 960 


Val Val Leu Lys Gln Thr Tyr Gln Glu Lys Val Cys Gly Leu Cys Gly 
                965                 970                 975     


Asn Phe Asp Gly Ile Gln Asn Asn Asp Leu Thr Ser Ser Asn Leu Gln 
            980                 985                 990         


Val Glu Glu Asp Pro Val Asp Phe  Gly Asn Ser Trp Lys  Val Ser Ser 
        995                 1000                 1005             


Gln Cys  Ala Asp Thr Arg Lys  Val Pro Leu Asp Ser  Ser Pro Ala 
    1010                 1015                 1020             


Thr Cys  His Asn Asn Ile Met  Lys Gln Thr Met Val  Asp Ser Ser 
    1025                 1030                 1035             


Cys Arg  Ile Leu Thr Ser Asp  Val Phe Gln Asp Cys  Asn Lys Leu 
    1040                 1045                 1050             


Val Asp  Pro Glu Pro Tyr Leu  Asp Val Cys Ile Tyr  Asp Thr Cys 
    1055                 1060                 1065             


Ser Cys  Glu Ser Ile Gly Asp  Cys Ala Cys Phe Cys  Asp Thr Ile 
    1070                 1075                 1080             


Ala Ala  Tyr Ala His Val Cys  Ala Gln His Gly Lys  Val Val Thr 
    1085                 1090                 1095             


Trp Arg  Thr Ala Thr Leu Cys  Pro Gln Ser Cys Glu  Glu Arg Asn 
    1100                 1105                 1110             


Leu Arg  Glu Asn Gly Tyr Glu  Cys Glu Trp Arg Tyr  Asn Ser Cys 
    1115                 1120                 1125             


Ala Pro  Ala Cys Gln Val Thr  Cys Gln His Pro Glu  Pro Leu Ala 
    1130                 1135                 1140             


Cys Pro  Val Gln Cys Val Glu  Gly Cys His Ala His  Cys Pro Pro 
    1145                 1150                 1155             


Gly Lys  Ile Leu Asp Glu Leu  Leu Gln Thr Cys Val  Asp Pro Glu 
    1160                 1165                 1170             


Asp Cys  Pro Val Cys Glu Val  Ala Gly Arg Arg Phe  Ala Ser Gly 
    1175                 1180                 1185             


Lys Lys  Val Thr Leu Asn Pro  Ser Asp Pro Glu His  Cys Gln Ile 
    1190                 1195                 1200             


Cys His  Cys Asp Val Val Asn  Leu Thr Cys Glu Ala  Cys Gln Glu 
    1205                 1210                 1215             


Pro Gly  Gly Leu Val Val Pro  Pro Thr Asp Ala Pro  Val Ser Pro 
    1220                 1225                 1230             


Thr Thr  Leu Tyr Val Glu Asp  Ile Ser Glu Pro Pro  Leu His Asp 
    1235                 1240                 1245             


Phe Tyr  Cys Ser Arg Leu Leu  Asp Leu Val Phe Leu  Leu Asp Gly 
    1250                 1255                 1260             


Ser Ser  Arg Leu Ser Glu Ala  Glu Phe Glu Val Leu  Lys Ala Phe 
    1265                 1270                 1275             


Val Val  Asp Met Met Glu Arg  Leu Arg Ile Ser Gln  Lys Trp Val 
    1280                 1285                 1290             


Arg Val  Ala Val Val Glu Tyr  His Asp Gly Ser His  Ala Tyr Ile 
    1295                 1300                 1305             


Gly Leu  Lys Asp Arg Lys Arg  Pro Ser Glu Leu Arg  Arg Ile Ala 
    1310                 1315                 1320             


Ser Gln  Val Lys Tyr Ala Gly  Ser Gln Val Ala Ser  Thr Ser Glu 
    1325                 1330                 1335             


Val Leu  Lys Tyr Thr Leu Phe  Gln Ile Phe Ser Lys  Ile Asp Arg 
    1340                 1345                 1350             


Pro Glu  Ala Ser Arg Ile Thr  Leu Leu Leu Met Ala  Ser Gln Glu 
    1355                 1360                 1365             


Pro Gln  Arg Met Ser Arg Asn  Phe Val Arg Tyr Val  Gln Gly Leu 
    1370                 1375                 1380             


Lys Lys  Lys Lys Val Ile Val  Ile Pro Val Gly Ile  Gly Pro His 
    1385                 1390                 1395             


Ala Asn  Leu Lys Gln Ile Arg  Leu Ile Glu Lys Gln  Ala Pro Glu 
    1400                 1405                 1410             


Asn Lys  Ala Phe Val Leu Ser  Ser Val Asp Glu Leu  Glu Gln Gln 
    1415                 1420                 1425             


Arg Asp  Glu Ile Val Ser Tyr  Leu Cys Asp Leu Ala  Pro Glu Ala 
    1430                 1435                 1440             


Pro Pro  Pro Thr Leu Pro Pro  Asp Met Ala Gln Val  Thr Val Gly 
    1445                 1450                 1455             


Pro Gly  Leu Leu Gly Val Ser  Thr Leu Gly Pro Lys  Arg Asn Ser 
    1460                 1465                 1470             


Met Val  Leu Asp Val Ala Phe  Val Leu Glu Gly Ser  Asp Lys Ile 
    1475                 1480                 1485             


Gly Glu  Ala Asp Phe Asn Arg  Ser Lys Glu Phe Met  Glu Glu Val 
    1490                 1495                 1500             


Ile Gln  Arg Met Asp Val Gly  Gln Asp Ser Ile His  Val Thr Val 
    1505                 1510                 1515             


Leu Gln  Tyr Ser Tyr Met Val  Thr Val Glu Tyr Pro  Phe Ser Glu 
    1520                 1525                 1530             


Ala Gln  Ser Lys Gly Asp Ile  Leu Gln Arg Val Arg  Glu Ile Arg 
    1535                 1540                 1545             


Tyr Gln  Gly Gly Asn Arg Thr  Asn Thr Gly Leu Ala  Leu Arg Tyr 
    1550                 1555                 1560             


Leu Ser  Asp His Ser Phe Leu  Val Ser Gln Gly Asp  Arg Glu Gln 
    1565                 1570                 1575             


Ala Pro  Asn Leu Val Tyr Met  Val Thr Gly Asn Pro  Ala Ser Asp 
    1580                 1585                 1590             


Glu Ile  Lys Arg Leu Pro Gly  Asp Ile Gln Val Val  Pro Ile Gly 
    1595                 1600                 1605             


Val Gly  Pro Asn Ala Asn Val  Gln Glu Leu Glu Arg  Ile Gly Trp 
    1610                 1615                 1620             


Pro Asn  Ala Pro Ile Leu Ile  Gln Asp Phe Glu Thr  Leu Pro Arg 
    1625                 1630                 1635             


Glu Ala  Pro Asp Leu Val Leu  Gln Arg Cys Cys Ser  Gly Glu Gly 
    1640                 1645                 1650             


Leu Gln  Ile Pro Thr Leu Ser  Pro Ala Pro Asp Cys  Ser Gln Pro 
    1655                 1660                 1665             


Leu Asp  Val Ile Leu Leu Leu  Asp Gly Ser Ser Ser  Phe Pro Ala 
    1670                 1675                 1680             


Ser Tyr  Phe Asp Glu Met Lys  Ser Phe Ala Lys Ala  Phe Ile Ser 
    1685                 1690                 1695             


Lys Ala  Asn Ile Gly Pro Arg  Leu Thr Gln Val Ser  Val Leu Gln 
    1700                 1705                 1710             


Tyr Gly  Ser Ile Thr Thr Ile  Asp Val Pro Trp Asn  Val Val Pro 
    1715                 1720                 1725             


Glu Lys  Ala His Leu Leu Ser  Leu Val Asp Val Met  Gln Arg Glu 
    1730                 1735                 1740             


Gly Gly  Pro Ser Gln Ile Gly  Asp Ala Leu Gly Phe  Ala Val Arg 
    1745                 1750                 1755             


Tyr Leu  Thr Ser Glu Met His  Gly Ala Arg Pro Gly  Ala Ser Lys 
    1760                 1765                 1770             


Ala Val  Val Ile Leu Val Thr  Asp Val Ser Val Asp  Ser Val Asp 
    1775                 1780                 1785             


Ala Ala  Ala Asp Ala Ala Arg  Ser Asn Arg Val Thr  Val Phe Pro 
    1790                 1795                 1800             


Ile Gly  Ile Gly Asp Arg Tyr  Asp Ala Ala Gln Leu  Arg Ile Leu 
    1805                 1810                 1815             


Ala Gly  Pro Ala Gly Asp Ser  Asn Val Val Lys Leu  Gln Arg Ile 
    1820                 1825                 1830             


Glu Asp  Leu Pro Thr Met Val  Thr Leu Gly Asn Ser  Phe Leu His 
    1835                 1840                 1845             


Lys Leu  Cys Ser Gly Phe Val  Arg Ile Cys Met Asp  Glu Asp Gly 
    1850                 1855                 1860             


Asn Glu  Lys Arg Pro Gly Asp  Val Trp Thr Leu Pro  Asp Gln Cys 
    1865                 1870                 1875             


His Thr  Val Thr Cys Gln Pro  Asp Gly Gln Thr Leu  Leu Lys Ser 
    1880                 1885                 1890             


His Arg  Val Asn Cys Asp Arg  Gly Leu Arg Pro Ser  Cys Pro Asn 
    1895                 1900                 1905             


Ser Gln  Ser Pro Val Lys Val  Glu Glu Thr Cys Gly  Cys Arg Trp 
    1910                 1915                 1920             


Thr Cys  Pro Cys Val Cys Thr  Gly Ser Ser Thr Arg  His Ile Val 
    1925                 1930                 1935             


Thr Phe  Asp Gly Gln Asn Phe  Lys Leu Thr Gly Ser  Cys Ser Tyr 
    1940                 1945                 1950             


Val Leu  Phe Gln Asn Lys Glu  Gln Asp Leu Glu Val  Ile Leu His 
    1955                 1960                 1965             


Asn Gly  Ala Cys Ser Pro Gly  Ala Arg Gln Gly Cys  Met Lys Ser 
    1970                 1975                 1980             


Ile Glu  Val Lys His Ser Ala  Leu Ser Val Glu Leu  His Ser Asp 
    1985                 1990                 1995             


Met Glu  Val Thr Val Asn Gly  Arg Leu Val Ser Val  Pro Tyr Val 
    2000                 2005                 2010             


Gly Gly  Asn Met Glu Val Asn  Val Tyr Gly Ala Ile  Met His Glu 
    2015                 2020                 2025             


Val Arg  Phe Asn His Leu Gly  His Ile Phe Thr Phe  Thr Pro Gln 
    2030                 2035                 2040             


Asn Asn  Glu Phe Gln Leu Gln  Leu Ser Pro Lys Thr  Phe Ala Ser 
    2045                 2050                 2055             


Lys Thr  Tyr Gly Leu Cys Gly  Ile Cys Asp Glu Asn  Gly Ala Asn 
    2060                 2065                 2070             


Asp Phe  Met Leu Arg Asp Gly  Thr Val Thr Thr Asp  Trp Lys Thr 
    2075                 2080                 2085             


Leu Val  Gln Glu Trp Thr Val  Gln Arg Pro Gly Gln  Thr Cys Gln 
    2090                 2095                 2100             


Pro Glu  Gln Cys Leu Val Pro  Asp Ser Ser His Cys  Gln Val Leu 
    2105                 2110                 2115             


Leu Leu  Pro Leu Phe Ala Glu  Cys His Lys Val Leu  Ala Pro Ala 
    2120                 2125                 2130             


Thr Phe  Tyr Ala Ile Cys Gln  Gln Asp Ser Cys His  Gln Glu Gln 
    2135                 2140                 2145             


Val Cys  Glu Val Ile Ala Ser  Tyr Ala His Leu Cys  Arg Thr Asn 
    2150                 2155                 2160             


Gly Val  Cys Val Asp Trp Arg  Thr Pro Asp Phe Cys  Ala Met Ser 
    2165                 2170                 2175             


Cys Pro  Pro Ser Leu Val Tyr  Asn His Cys Glu His  Gly Cys Pro 
    2180                 2185                 2190             


Arg His  Cys Asp Gly Asn Val  Ser Ser Cys Gly Asp  His Pro Ser 
    2195                 2200                 2205             


Glu Gly  Cys Phe Cys Pro Pro  Asp Lys Val Met Leu  Glu Gly Ser 
    2210                 2215                 2220             


Cys Val  Pro Glu Glu Ala Cys  Thr Gln Cys Ile Gly  Glu Asp Gly 
    2225                 2230                 2235             


Val Gln  His Gln Phe Leu Glu  Ala Trp Val Pro Asp  His Gln Pro 
    2240                 2245                 2250             


Cys Gln  Ile Cys Thr Cys Leu  Ser Gly Arg Lys Val  Asn Cys Thr 
    2255                 2260                 2265             


Thr Gln  Pro Cys Pro Thr Ala  Lys Ala Pro Thr Cys  Gly Leu Cys 
    2270                 2275                 2280             


Glu Val  Ala Arg Leu Arg Gln  Asn Ala Asp Gln Cys  Cys Pro Glu 
    2285                 2290                 2295             


Tyr Glu  Cys Val Cys Asp Pro  Val Ser Cys Asp Leu  Pro Pro Val 
    2300                 2305                 2310             


Pro His  Cys Glu Arg Gly Leu  Gln Pro Thr Leu Thr  Asn Pro Gly 
    2315                 2320                 2325             


Glu Cys  Arg Pro Asn Phe Thr  Cys Ala Cys Arg Lys  Glu Glu Cys 
    2330                 2335                 2340             


Lys Arg  Val Ser Pro Pro Ser  Cys Pro Pro His Arg  Leu Pro Thr 
    2345                 2350                 2355             


Leu Arg  Lys Thr Gln Cys Cys  Asp Glu Tyr Glu Cys  Ala Cys Asn 
    2360                 2365                 2370             


Cys Val  Asn Ser Thr Val Ser  Cys Pro Leu Gly Tyr  Leu Ala Ser 
    2375                 2380                 2385             


Thr Ala  Thr Asn Asp Cys Gly  Cys Thr Thr Thr Thr  Cys Leu Pro 
    2390                 2395                 2400             


Asp Lys  Val Cys Val His Arg  Ser Thr Ile Tyr Pro  Val Gly Gln 
    2405                 2410                 2415             


Phe Trp  Glu Glu Gly Cys Asp  Val Cys Thr Cys Thr  Asp Met Glu 
    2420                 2425                 2430             


Asp Ala  Val Met Gly Leu Arg  Val Ala Gln Cys Ser  Gln Lys Pro 
    2435                 2440                 2445             


Cys Glu  Asp Ser Cys Arg Ser  Gly Phe Thr Tyr Val  Leu His Glu 
    2450                 2455                 2460             


Gly Glu  Cys Cys Gly Arg Cys  Leu Pro Ser Ala Cys  Glu Val Val 
    2465                 2470                 2475             


Thr Gly  Ser Pro Arg Gly Asp  Ser Gln Ser Ser Trp  Lys Ser Val 
    2480                 2485                 2490             


Gly Ser  Gln Trp Glu Asn Pro  Cys Leu Ile Asn Glu  Cys Val Arg 
    2495                 2500                 2505             


Val Lys  Glu Glu Val Phe Ile  Gln Gln Arg Asn Val  Ser Cys Pro 
    2510                 2515                 2520             


Gln Leu  Glu Val Pro Val Cys  Pro Ser Gly Phe Gln  Leu Ser Cys 
    2525                 2530                 2535             


Lys Thr  Ser Ala Cys Cys Pro  Ser Cys Arg Cys Glu  Arg Met Glu 
    2540                 2545                 2550             


Ala Cys  Met Leu Asn Gly Thr  Val Ile Gly Pro Gly  Lys Thr Val 
    2555                 2560                 2565             


Met Ile  Asp Val Cys Thr Thr  Cys Arg Cys Met Val  Gln Val Gly 
    2570                 2575                 2580             


Val Ile  Ser Gly Phe Lys Leu  Glu Cys Arg Lys Thr  Thr Cys Asn 
    2585                 2590                 2595             


Pro Cys  Pro Leu Gly Tyr Lys  Glu Glu Asn Asn Thr  Gly Glu Cys 
    2600                 2605                 2610             


Cys Gly  Arg Cys Leu Pro Thr  Ala Cys Thr Ile Gln  Leu Arg Gly 
    2615                 2620                 2625             


Gly Gln  Ile Met Thr Leu Lys  Arg Asp Glu Thr Leu  Gln Asp Gly 
    2630                 2635                 2640             


Cys Asp  Thr His Phe Cys Lys  Val Asn Glu Arg Gly  Glu Tyr Phe 
    2645                 2650                 2655             


Trp Glu  Lys Arg Val Thr Gly  Cys Pro Pro Phe Asp  Glu His Lys 
    2660                 2665                 2670             


Cys Leu  Ala Glu Gly Gly Lys  Ile Met Lys Ile Pro  Gly Thr Cys 
    2675                 2680                 2685             


Cys Asp  Thr Cys Glu Glu Pro  Glu Cys Asn Asp Ile  Thr Ala Arg 
    2690                 2695                 2700             


Leu Gln  Tyr Val Lys Val Gly  Ser Cys Lys Ser Glu  Val Glu Val 
    2705                 2710                 2715             


Asp Ile  His Tyr Cys Gln Gly  Lys Cys Ala Ser Lys  Ala Met Tyr 
    2720                 2725                 2730             


Ser Ile  Asp Ile Asn Asp Val  Gln Asp Gln Cys Ser  Cys Cys Ser 
    2735                 2740                 2745             


Pro Thr  Arg Thr Glu Pro Met  Gln His Cys Thr Asn  Gly Ser Val 
    2750                 2755                 2760             


Val Tyr  His Glu Val Leu Asn  Ala Met Glu Cys Lys  Cys Ser Pro 
    2765                 2770                 2775             


Arg Lys  Cys Ser Lys 
    2780             


<210>  3
<211>  2050
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide


<220>
<221>  MISC_FEATURE
<223>  mature vWF

<400>  3

Ser Leu Ser Cys Arg Pro Pro Met Val Lys Leu Val Cys Pro Ala Asp 
1               5                   10                  15      


Asn Leu Arg Ala Glu Gly Leu Glu Cys Thr Lys Thr Cys Gln Asn Tyr 
            20                  25                  30          


Asp Leu Glu Cys Met Ser Met Gly Cys Val Ser Gly Cys Leu Cys Pro 
        35                  40                  45              


Pro Gly Met Val Arg His Glu Asn Arg Cys Val Ala Leu Glu Arg Cys 
    50                  55                  60                  


Pro Cys Phe His Gln Gly Lys Glu Tyr Ala Pro Gly Glu Thr Val Lys 
65                  70                  75                  80  


Ile Gly Cys Asn Thr Cys Val Cys Arg Asp Arg Lys Trp Asn Cys Thr 
                85                  90                  95      


Asp His Val Cys Asp Ala Thr Cys Ser Thr Ile Gly Met Ala His Tyr 
            100                 105                 110         


Leu Thr Phe Asp Gly Leu Lys Tyr Leu Phe Pro Gly Glu Cys Gln Tyr 
        115                 120                 125             


Val Leu Val Gln Asp Tyr Cys Gly Ser Asn Pro Gly Thr Phe Arg Ile 
    130                 135                 140                 


Leu Val Gly Asn Lys Gly Cys Ser His Pro Ser Val Lys Cys Lys Lys 
145                 150                 155                 160 


Arg Val Thr Ile Leu Val Glu Gly Gly Glu Ile Glu Leu Phe Asp Gly 
                165                 170                 175     


Glu Val Asn Val Lys Arg Pro Met Lys Asp Glu Thr His Phe Glu Val 
            180                 185                 190         


Val Glu Ser Gly Arg Tyr Ile Ile Leu Leu Leu Gly Lys Ala Leu Ser 
        195                 200                 205             


Val Val Trp Asp Arg His Leu Ser Ile Ser Val Val Leu Lys Gln Thr 
    210                 215                 220                 


Tyr Gln Glu Lys Val Cys Gly Leu Cys Gly Asn Phe Asp Gly Ile Gln 
225                 230                 235                 240 


Asn Asn Asp Leu Thr Ser Ser Asn Leu Gln Val Glu Glu Asp Pro Val 
                245                 250                 255     


Asp Phe Gly Asn Ser Trp Lys Val Ser Ser Gln Cys Ala Asp Thr Arg 
            260                 265                 270         


Lys Val Pro Leu Asp Ser Ser Pro Ala Thr Cys His Asn Asn Ile Met 
        275                 280                 285             


Lys Gln Thr Met Val Asp Ser Ser Cys Arg Ile Leu Thr Ser Asp Val 
    290                 295                 300                 


Phe Gln Asp Cys Asn Lys Leu Val Asp Pro Glu Pro Tyr Leu Asp Val 
305                 310                 315                 320 


Cys Ile Tyr Asp Thr Cys Ser Cys Glu Ser Ile Gly Asp Cys Ala Cys 
                325                 330                 335     


Phe Cys Asp Thr Ile Ala Ala Tyr Ala His Val Cys Ala Gln His Gly 
            340                 345                 350         


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


Glu Arg Asn Leu Arg Glu Asn Gly Tyr Glu Cys Glu Trp Arg Tyr Asn 
    370                 375                 380                 


Ser Cys Ala Pro Ala Cys Gln Val Thr Cys Gln His Pro Glu Pro Leu 
385                 390                 395                 400 


Ala Cys Pro Val Gln Cys Val Glu Gly Cys His Ala His Cys Pro Pro 
                405                 410                 415     


Gly Lys Ile Leu Asp Glu Leu Leu Gln Thr Cys Val Asp Pro Glu Asp 
            420                 425                 430         


Cys Pro Val Cys Glu Val Ala Gly Arg Arg Phe Ala Ser Gly Lys Lys 
        435                 440                 445             


Val Thr Leu Asn Pro Ser Asp Pro Glu His Cys Gln Ile Cys His Cys 
    450                 455                 460                 


Asp Val Val Asn Leu Thr Cys Glu Ala Cys Gln Glu Pro Gly Gly Leu 
465                 470                 475                 480 


Val Val Pro Pro Thr Asp Ala Pro Val Ser Pro Thr Thr Leu Tyr Val 
                485                 490                 495     


Glu Asp Ile Ser Glu Pro Pro Leu His Asp Phe Tyr Cys Ser Arg Leu 
            500                 505                 510         


Leu Asp Leu Val Phe Leu Leu Asp Gly Ser Ser Arg Leu Ser Glu Ala 
        515                 520                 525             


Glu Phe Glu Val Leu Lys Ala Phe Val Val Asp Met Met Glu Arg Leu 
    530                 535                 540                 


Arg Ile Ser Gln Lys Trp Val Arg Val Ala Val Val Glu Tyr His Asp 
545                 550                 555                 560 


Gly Ser His Ala Tyr Ile Gly Leu Lys Asp Arg Lys Arg Pro Ser Glu 
                565                 570                 575     


Leu Arg Arg Ile Ala Ser Gln Val Lys Tyr Ala Gly Ser Gln Val Ala 
            580                 585                 590         


Ser Thr Ser Glu Val Leu Lys Tyr Thr Leu Phe Gln Ile Phe Ser Lys 
        595                 600                 605             


Ile Asp Arg Pro Glu Ala Ser Arg Ile Thr Leu Leu Leu Met Ala Ser 
    610                 615                 620                 


Gln Glu Pro Gln Arg Met Ser Arg Asn Phe Val Arg Tyr Val Gln Gly 
625                 630                 635                 640 


Leu Lys Lys Lys Lys Val Ile Val Ile Pro Val Gly Ile Gly Pro His 
                645                 650                 655     


Ala Asn Leu Lys Gln Ile Arg Leu Ile Glu Lys Gln Ala Pro Glu Asn 
            660                 665                 670         


Lys Ala Phe Val Leu Ser Ser Val Asp Glu Leu Glu Gln Gln Arg Asp 
        675                 680                 685             


Glu Ile Val Ser Tyr Leu Cys Asp Leu Ala Pro Glu Ala Pro Pro Pro 
    690                 695                 700                 


Thr Leu Pro Pro Asp Met Ala Gln Val Thr Val Gly Pro Gly Leu Leu 
705                 710                 715                 720 


Gly Val Ser Thr Leu Gly Pro Lys Arg Asn Ser Met Val Leu Asp Val 
                725                 730                 735     


Ala Phe Val Leu Glu Gly Ser Asp Lys Ile Gly Glu Ala Asp Phe Asn 
            740                 745                 750         


Arg Ser Lys Glu Phe Met Glu Glu Val Ile Gln Arg Met Asp Val Gly 
        755                 760                 765             


Gln Asp Ser Ile His Val Thr Val Leu Gln Tyr Ser Tyr Met Val Thr 
    770                 775                 780                 


Val Glu Tyr Pro Phe Ser Glu Ala Gln Ser Lys Gly Asp Ile Leu Gln 
785                 790                 795                 800 


Arg Val Arg Glu Ile Arg Tyr Gln Gly Gly Asn Arg Thr Asn Thr Gly 
                805                 810                 815     


Leu Ala Leu Arg Tyr Leu Ser Asp His Ser Phe Leu Val Ser Gln Gly 
            820                 825                 830         


Asp Arg Glu Gln Ala Pro Asn Leu Val Tyr Met Val Thr Gly Asn Pro 
        835                 840                 845             


Ala Ser Asp Glu Ile Lys Arg Leu Pro Gly Asp Ile Gln Val Val Pro 
    850                 855                 860                 


Ile Gly Val Gly Pro Asn Ala Asn Val Gln Glu Leu Glu Arg Ile Gly 
865                 870                 875                 880 


Trp Pro Asn Ala Pro Ile Leu Ile Gln Asp Phe Glu Thr Leu Pro Arg 
                885                 890                 895     


Glu Ala Pro Asp Leu Val Leu Gln Arg Cys Cys Ser Gly Glu Gly Leu 
            900                 905                 910         


Gln Ile Pro Thr Leu Ser Pro Ala Pro Asp Cys Ser Gln Pro Leu Asp 
        915                 920                 925             


Val Ile Leu Leu Leu Asp Gly Ser Ser Ser Phe Pro Ala Ser Tyr Phe 
    930                 935                 940                 


Asp Glu Met Lys Ser Phe Ala Lys Ala Phe Ile Ser Lys Ala Asn Ile 
945                 950                 955                 960 


Gly Pro Arg Leu Thr Gln Val Ser Val Leu Gln Tyr Gly Ser Ile Thr 
                965                 970                 975     


Thr Ile Asp Val Pro Trp Asn Val Val Pro Glu Lys Ala His Leu Leu 
            980                 985                 990         


Ser Leu Val Asp Val Met Gln Arg  Glu Gly Gly Pro Ser  Gln Ile Gly 
        995                 1000                 1005             


Asp Ala  Leu Gly Phe Ala Val  Arg Tyr Leu Thr Ser  Glu Met His 
    1010                 1015                 1020             


Gly Ala  Arg Pro Gly Ala Ser  Lys Ala Val Val Ile  Leu Val Thr 
    1025                 1030                 1035             


Asp Val  Ser Val Asp Ser Val  Asp Ala Ala Ala Asp  Ala Ala Arg 
    1040                 1045                 1050             


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


Asp Ala  Ala Gln Leu Arg Ile  Leu Ala Gly Pro Ala  Gly Asp Ser 
    1070                 1075                 1080             


Asn Val  Val Lys Leu Gln Arg  Ile Glu Asp Leu Pro  Thr Met Val 
    1085                 1090                 1095             


Thr Leu  Gly Asn Ser Phe Leu  His Lys Leu Cys Ser  Gly Phe Val 
    1100                 1105                 1110             


Arg Ile  Cys Met Asp Glu Asp  Gly Asn Glu Lys Arg  Pro Gly Asp 
    1115                 1120                 1125             


Val Trp  Thr Leu Pro Asp Gln  Cys His Thr Val Thr  Cys Gln Pro 
    1130                 1135                 1140             


Asp Gly  Gln Thr Leu Leu Lys  Ser His Arg Val Asn  Cys Asp Arg 
    1145                 1150                 1155             


Gly Leu  Arg Pro Ser Cys Pro  Asn Ser Gln Ser Pro  Val Lys Val 
    1160                 1165                 1170             


Glu Glu  Thr Cys Gly Cys Arg  Trp Thr Cys Pro Cys  Val Cys Thr 
    1175                 1180                 1185             


Gly Ser  Ser Thr Arg His Ile  Val Thr Phe Asp Gly  Gln Asn Phe 
    1190                 1195                 1200             


Lys Leu  Thr Gly Ser Cys Ser  Tyr Val Leu Phe Gln  Asn Lys Glu 
    1205                 1210                 1215             


Gln Asp  Leu Glu Val Ile Leu  His Asn Gly Ala Cys  Ser Pro Gly 
    1220                 1225                 1230             


Ala Arg  Gln Gly Cys Met Lys  Ser Ile Glu Val Lys  His Ser Ala 
    1235                 1240                 1245             


Leu Ser  Val Glu Leu His Ser  Asp Met Glu Val Thr  Val Asn Gly 
    1250                 1255                 1260             


Arg Leu  Val Ser Val Pro Tyr  Val Gly Gly Asn Met  Glu Val Asn 
    1265                 1270                 1275             


Val Tyr  Gly Ala Ile Met His  Glu Val Arg Phe Asn  His Leu Gly 
    1280                 1285                 1290             


His Ile  Phe Thr Phe Thr Pro  Gln Asn Asn Glu Phe  Gln Leu Gln 
    1295                 1300                 1305             


Leu Ser  Pro Lys Thr Phe Ala  Ser Lys Thr Tyr Gly  Leu Cys Gly 
    1310                 1315                 1320             


Ile Cys  Asp Glu Asn Gly Ala  Asn Asp Phe Met Leu  Arg Asp Gly 
    1325                 1330                 1335             


Thr Val  Thr Thr Asp Trp Lys  Thr Leu Val Gln Glu  Trp Thr Val 
    1340                 1345                 1350             


Gln Arg  Pro Gly Gln Thr Cys  Gln Pro Ile Leu Glu  Glu Gln Cys 
    1355                 1360                 1365             


Leu Val  Pro Asp Ser Ser His  Cys Gln Val Leu Leu  Leu Pro Leu 
    1370                 1375                 1380             


Phe Ala  Glu Cys His Lys Val  Leu Ala Pro Ala Thr  Phe Tyr Ala 
    1385                 1390                 1395             


Ile Cys  Gln Gln Asp Ser Cys  His Gln Glu Gln Val  Cys Glu Val 
    1400                 1405                 1410             


Ile Ala  Ser Tyr Ala His Leu  Cys Arg Thr Asn Gly  Val Cys Val 
    1415                 1420                 1425             


Asp Trp  Arg Thr Pro Asp Phe  Cys Ala Met Ser Cys  Pro Pro Ser 
    1430                 1435                 1440             


Leu Val  Tyr Asn His Cys Glu  His Gly Cys Pro Arg  His Cys Asp 
    1445                 1450                 1455             


Gly Asn  Val Ser Ser Cys Gly  Asp His Pro Ser Glu  Gly Cys Phe 
    1460                 1465                 1470             


Cys Pro  Pro Asp Lys Val Met  Leu Glu Gly Ser Cys  Val Pro Glu 
    1475                 1480                 1485             


Glu Ala  Cys Thr Gln Cys Ile  Gly Glu Asp Gly Val  Gln His Gln 
    1490                 1495                 1500             


Phe Leu  Glu Ala Trp Val Pro  Asp His Gln Pro Cys  Gln Ile Cys 
    1505                 1510                 1515             


Thr Cys  Leu Ser Gly Arg Lys  Val Asn Cys Thr Thr  Gln Pro Cys 
    1520                 1525                 1530             


Pro Thr  Ala Lys Ala Pro Thr  Cys Gly Leu Cys Glu  Val Ala Arg 
    1535                 1540                 1545             


Leu Arg  Gln Asn Ala Asp Gln  Cys Cys Pro Glu Tyr  Glu Cys Val 
    1550                 1555                 1560             


Cys Asp  Pro Val Ser Cys Asp  Leu Pro Pro Val Pro  His Cys Glu 
    1565                 1570                 1575             


Arg Gly  Leu Gln Pro Thr Leu  Thr Asn Pro Gly Glu  Cys Arg Pro 
    1580                 1585                 1590             


Asn Phe  Thr Cys Ala Cys Arg  Lys Glu Glu Cys Lys  Arg Val Ser 
    1595                 1600                 1605             


Pro Pro  Ser Cys Pro Pro His  Arg Leu Pro Thr Leu  Arg Lys Thr 
    1610                 1615                 1620             


Gln Cys  Cys Asp Glu Tyr Glu  Cys Ala Cys Asn Cys  Val Asn Ser 
    1625                 1630                 1635             


Thr Val  Ser Cys Pro Leu Gly  Tyr Leu Ala Ser Thr  Ala Thr Asn 
    1640                 1645                 1650             


Asp Cys  Gly Cys Thr Thr Thr  Thr Cys Leu Pro Asp  Lys Val Cys 
    1655                 1660                 1665             


Val His  Arg Ser Thr Ile Tyr  Pro Val Gly Gln Phe  Trp Glu Glu 
    1670                 1675                 1680             


Gly Cys  Asp Val Cys Thr Cys  Thr Asp Met Glu Asp  Ala Val Met 
    1685                 1690                 1695             


Gly Leu  Arg Val Ala Gln Cys  Ser Gln Lys Pro Cys  Glu Asp Ser 
    1700                 1705                 1710             


Cys Arg  Ser Gly Phe Thr Tyr  Val Leu His Glu Gly  Glu Cys Cys 
    1715                 1720                 1725             


Gly Arg  Cys Leu Pro Ser Ala  Cys Glu Val Val Thr  Gly Ser Pro 
    1730                 1735                 1740             


Arg Gly  Asp Ser Gln Ser Ser  Trp Lys Ser Val Gly  Ser Gln Trp 
    1745                 1750                 1755             


Ala Ser  Pro Glu Asn Pro Cys  Leu Ile Asn Glu Cys  Val Arg Val 
    1760                 1765                 1770             


Lys Glu  Glu Val Phe Ile Gln  Gln Arg Asn Val Ser  Cys Pro Gln 
    1775                 1780                 1785             


Leu Glu  Val Pro Val Cys Pro  Ser Gly Phe Gln Leu  Ser Cys Lys 
    1790                 1795                 1800             


Thr Ser  Ala Cys Cys Pro Ser  Cys Arg Cys Glu Arg  Met Glu Ala 
    1805                 1810                 1815             


Cys Met  Leu Asn Gly Thr Val  Ile Gly Pro Gly Lys  Thr Val Met 
    1820                 1825                 1830             


Ile Asp  Val Cys Thr Thr Cys  Arg Cys Met Val Gln  Val Gly Val 
    1835                 1840                 1845             


Ile Ser  Gly Phe Lys Leu Glu  Cys Arg Lys Thr Thr  Cys Asn Pro 
    1850                 1855                 1860             


Cys Pro  Leu Gly Tyr Lys Glu  Glu Asn Asn Thr Gly  Glu Cys Cys 
    1865                 1870                 1875             


Gly Arg  Cys Leu Pro Thr Ala  Cys Thr Ile Gln Leu  Arg Gly Gly 
    1880                 1885                 1890             


Gln Ile  Met Thr Leu Lys Arg  Asp Glu Thr Leu Gln  Asp Gly Cys 
    1895                 1900                 1905             


Asp Thr  His Phe Cys Lys Val  Asn Glu Arg Gly Glu  Tyr Phe Trp 
    1910                 1915                 1920             


Glu Lys  Arg Val Thr Gly Cys  Pro Pro Phe Asp Glu  His Lys Cys 
    1925                 1930                 1935             


Leu Ala  Glu Gly Gly Lys Ile  Met Lys Ile Pro Gly  Thr Cys Cys 
    1940                 1945                 1950             


Asp Thr  Cys Glu Glu Pro Glu  Cys Asn Asp Ile Thr  Ala Arg Leu 
    1955                 1960                 1965             


Gln Tyr  Val Lys Val Gly Ser  Cys Lys Ser Glu Val  Glu Val Asp 
    1970                 1975                 1980             


Ile His  Tyr Cys Gln Gly Lys  Cys Ala Ser Lys Ala  Met Tyr Ser 
    1985                 1990                 1995             


Ile Asp  Ile Asn Asp Val Gln  Asp Gln Cys Ser Cys  Cys Ser Pro 
    2000                 2005                 2010             


Thr Arg  Thr Glu Pro Met Gln  Val Ala Leu His Cys  Thr Asn Gly 
    2015                 2020                 2025             


Ser Val  Val Tyr His Glu Val  Leu Asn Ala Met Glu  Cys Lys Cys 
    2030                 2035                 2040             


Ser Pro  Arg Lys Cys Ser Lys  
    2045                 2050 


