                         SEQUENCE LISTING

<110>  CSL Behring GmbH
 
<120>  Von Willebrand Factor variants having improved Factor VIII 
       binding affinity

<130>  A187

<150>  EP12155509.8
<151>  2012-02-15

<160>  38    

<170>  PatentIn version 3.5

<210>  1
<211>  8442
<212>  DNA
<213>  Homo sapiens

<400>  1
atgattcctg ccagatttgc cggggtgctg cttgctctgg ccctcatttt gccagggacc       60

ctttgtgcag aaggaactcg cggcaggtca tccacggccc gatgcagcct tttcggaagt      120

gacttcgtca acacctttga tgggagcatg tacagctttg cgggatactg cagttacctc      180

ctggcagggg gctgccagaa acgctccttc tcgattattg gggacttcca gaatggcaag      240

agagtgagcc tctccgtgta tcttggggaa ttttttgaca tccatttgtt tgtcaatggt      300

accgtgacac agggggacca aagagtctcc atgccctatg cctccaaagg gctgtatcta      360

gaaactgagg ctgggtacta caagctgtcc ggtgaggcct atggctttgt ggccaggatc      420

gatggcagcg gcaactttca agtcctgctg tcagacagat acttcaacaa gacctgcggg      480

ctgtgtggca actttaacat ctttgctgaa gatgacttta tgacccaaga agggaccttg      540

acctcggacc cttatgactt tgccaactca tgggctctga gcagtggaga acagtggtgt      600

gaacgggcat ctcctcccag cagctcatgc aacatctcct ctggggaaat gcagaagggc      660

ctgtgggagc agtgccagct tctgaagagc acctcggtgt ttgcccgctg ccaccctctg      720

gtggaccccg agccttttgt ggccctgtgt gagaagactt tgtgtgagtg tgctgggggg      780

ctggagtgcg cctgccctgc cctcctggag tacgcccgga cctgtgccca ggagggaatg      840

gtgctgtacg gctggaccga ccacagcgcg tgcagcccag tgtgccctgc tggtatggag      900

tataggcagt gtgtgtcccc ttgcgccagg acctgccaga gcctgcacat caatgaaatg      960

tgtcaggagc gatgcgtgga tggctgcagc tgccctgagg gacagctcct ggatgaaggc     1020

ctctgcgtgg agagcaccga gtgtccctgc gtgcattccg gaaagcgcta ccctcccggc     1080

acctccctct ctcgagactg caacacctgc atttgccgaa acagccagtg gatctgcagc     1140

aatgaagaat gtccagggga gtgccttgtc acaggtcaat cacacttcaa gagctttgac     1200

aacagatact tcaccttcag tgggatctgc cagtacctgc tggcccggga ttgccaggac     1260

cactccttct ccattgtcat tgagactgtc cagtgtgctg atgaccgcga cgctgtgtgc     1320

acccgctccg tcaccgtccg gctgcctggc ctgcacaaca gccttgtgaa actgaagcat     1380

ggggcaggag ttgccatgga tggccaggac gtccagctcc ccctcctgaa aggtgacctc     1440

cgcatccagc atacagtgac ggcctccgtg cgcctcagct acggggagga cctgcagatg     1500

gactgggatg gccgcgggag gctgctggtg aagctgtccc ccgtctatgc cgggaagacc     1560

tgcggcctgt gtgggaatta caatggcaac cagggcgacg acttccttac cccctctggg     1620

ctggcggagc cccgggtgga ggacttcggg aacgcctgga agctgcacgg ggactgccag     1680

gacctgcaga agcagcacag cgatccctgc gccctcaacc cgcgcatgac caggttctcc     1740

gaggaggcgt gcgcggtcct gacgtccccc acattcgagg cctgccatcg tgccgtcagc     1800

ccgctgccct acctgcggaa ctgccgctac gacgtgtgct cctgctcgga cggccgcgag     1860

tgcctgtgcg gcgccctggc cagctatgcc gcggcctgcg cggggagagg cgtgcgcgtc     1920

gcgtggcgcg agccaggccg ctgtgagctg aactgcccga aaggccaggt gtacctgcag     1980

tgcgggaccc cctgcaacct gacctgccgc tctctctctt acccggatga ggaatgcaat     2040

gaggcctgcc tggagggctg cttctgcccc ccagggctct acatggatga gaggggggac     2100

tgcgtgccca aggcccagtg cccctgttac tatgacggtg agatcttcca gccagaagac     2160

atcttctcag accatcacac catgtgctac tgtgaggatg gcttcatgca ctgtaccatg     2220

agtggagtcc ccggaagctt gctgcctgac gctgtcctca gcagtcccct gtctcatcgc     2280

agcaaaagga gcctatcctg tcggcccccc atggtcaagc tggtgtgtcc cgctgacaac     2340

ctgcgggctg aagggctcga gtgtaccaaa acgtgccaga actatgacct ggagtgcatg     2400

agcatgggct gtgtctctgg ctgcctctgc cccccgggca tggtccggca tgagaacaga     2460

tgtgtggccc tggaaaggtg tccctgcttc catcagggca aggagtatgc ccctggagaa     2520

acagtgaaga ttggctgcaa cacttgtgtc tgtcgggacc ggaagtggaa ctgcacagac     2580

catgtgtgtg atgccacgtg ctccacgatc ggcatggccc actacctcac cttcgacggg     2640

ctcaaatacc tgttccccgg ggagtgccag tacgttctgg tgcaggatta ctgcggcagt     2700

aaccctggga cctttcggat cctagtgggg aataagggat gcagccaccc ctcagtgaaa     2760

tgcaagaaac gggtcaccat cctggtggag ggaggagaga ttgagctgtt tgacggggag     2820

gtgaatgtga agaggcccat gaaggatgag actcactttg aggtggtgga gtctggccgg     2880

tacatcattc tgctgctggg caaagccctc tccgtggtct gggaccgcca cctgagcatc     2940

tccgtggtcc tgaagcagac ataccaggag aaagtgtgtg gcctgtgtgg gaattttgat     3000

ggcatccaga acaatgacct caccagcagc aacctccaag tggaggaaga ccctgtggac     3060

tttgggaact cctggaaagt gagctcgcag tgtgctgaca ccagaaaagt gcctctggac     3120

tcatcccctg ccacctgcca taacaacatc atgaagcaga cgatggtgga ttcctcctgt     3180

agaatcctta ccagtgacgt cttccaggac tgcaacaagc tggtggaccc cgagccatat     3240

ctggatgtct gcatttacga cacctgctcc tgtgagtcca ttggggactg cgcctgcttc     3300

tgcgacacca ttgctgccta tgcccacgtg tgtgcccagc atggcaaggt ggtgacctgg     3360

aggacggcca cattgtgccc ccagagctgc gaggagagga atctccggga gaacgggtat     3420

gagtgtgagt ggcgctataa cagctgtgca cctgcctgtc aagtcacgtg tcagcaccct     3480

gagccactgg cctgccctgt gcagtgtgtg gagggctgcc atgcccactg ccctccaggg     3540

aaaatcctgg atgagctttt gcagacctgc gttgaccctg aagactgtcc agtgtgtgag     3600

gtggctggcc ggcgttttgc ctcaggaaag aaagtcacct tgaatcccag tgaccctgag     3660

cactgccaga tttgccactg tgatgttgtc aacctcacct gtgaagcctg ccaggagccg     3720

ggaggcctgg tggtgcctcc cacagatgcc ccggtgagcc ccaccactct gtatgtggag     3780

gacatctcgg aaccgccgtt gcacgatttc tactgcagca ggctactgga cctggtcttc     3840

ctgctggatg gctcctccag gctgtccgag gctgagtttg aagtgctgaa ggcctttgtg     3900

gtggacatga tggagcggct gcgcatctcc cagaagtggg tccgcgtggc cgtggtggag     3960

taccacgacg gctcccacgc ctacatcggg ctcaaggacc ggaagcgacc gtcagagctg     4020

cggcgcattg ccagccaggt gaagtatgcg ggcagccagg tggcctccac cagcgaggtc     4080

ttgaaataca cactgttcca aatcttcagc aagatcgacc gccctgaagc ctcccgcatc     4140

gccctgctcc tgatggccag ccaggagccc caacggatgt cccggaactt tgtccgctac     4200

gtccagggcc tgaagaagaa gaaggtcatt gtgatcccgg tgggcattgg gccccatgcc     4260

aacctcaagc agatccgcct catcgagaag caggcccctg agaacaaggc cttcgtgctg     4320

agcagtgtgg atgagctgga gcagcaaagg gacgagatcg ttagctacct ctgtgacctt     4380

gcccctgaag cccctcctcc tactctgccc ccccacatgg cacaagtcac tgtgggcccg     4440

gggctcttgg gggtttcgac cctggggccc aagaggaact ccatggttct ggatgtggcg     4500

ttcgtcctgg aaggatcgga caaaattggt gaagccgact tcaacaggag caaggagttc     4560

atggaggagg tgattcagcg gatggatgtg ggccaggaca gcatccacgt cacggtgctg     4620

cagtactcct acatggtgac cgtggagtac cccttcagcg aggcacagtc caaaggggac     4680

atcctgcagc gggtgcgaga gatccgctac cagggcggca acaggaccaa cactgggctg     4740

gccctgcggt acctctctga ccacagcttc ttggtcagcc agggtgaccg ggagcaggcg     4800

cccaacctgg tctacatggt caccggaaat cctgcctctg atgagatcaa gaggctgcct     4860

ggagacatcc aggtggtgcc cattggagtg ggccctaatg ccaacgtgca ggagctggag     4920

aggattggct ggcccaatgc ccctatcctc atccaggact ttgagacgct cccccgagag     4980

gctcctgacc tggtgctgca gaggtgctgc tccggagagg ggctgcagat ccccaccctc     5040

tcccctgcac ctgactgcag ccagcccctg gacgtgatcc ttctcctgga tggctcctcc     5100

agtttcccag cttcttattt tgatgaaatg aagagtttcg ccaaggcttt catttcaaaa     5160

gccaatatag ggcctcgtct cactcaggtg tcagtgctgc agtatggaag catcaccacc     5220

attgacgtgc catggaacgt ggtcccggag aaagcccatt tgctgagcct tgtggacgtc     5280

atgcagcggg agggaggccc cagccaaatc ggggatgcct tgggctttgc tgtgcgatac     5340

ttgacttcag aaatgcatgg ggcgcgcccg ggagcctcaa aggcggtggt catcctggtc     5400

acggacgtct ctgtggattc agtggatgca gcagctgatg ccgccaggtc caacagagtg     5460

acagtgttcc ctattggaat tggagatcgc tacgatgcag cccagctacg gatcttggca     5520

ggcccagcag gcgactccaa cgtggtgaag ctccagcgaa tcgaagacct ccctaccatg     5580

gtcaccttgg gcaattcctt cctccacaaa ctgtgctctg gatttgttag gatttgcatg     5640

gatgaggatg ggaatgagaa gaggcccggg gacgtctgga ccttgccaga ccagtgccac     5700

accgtgactt gccagccaga tggccagacc ttgctgaaga gtcatcgggt caactgtgac     5760

cgggggctga ggccttcgtg ccctaacagc cagtcccctg ttaaagtgga agagacctgt     5820

ggctgccgct ggacctgccc ctgcgtgtgc acaggcagct ccactcggca catcgtgacc     5880

tttgatgggc agaatttcaa gctgactggc agctgttctt atgtcctatt tcaaaacaag     5940

gagcaggacc tggaggtgat tctccataat ggtgcctgca gccctggagc aaggcagggc     6000

tgcatgaaat ccatcgaggt gaagcacagt gccctctccg tcgagctgca cagtgacatg     6060

gaggtgacgg tgaatgggag actggtctct gttccttacg tgggtgggaa catggaagtc     6120

aacgtttatg gtgccatcat gcatgaggtc agattcaatc accttggtca catcttcaca     6180

ttcactccac aaaacaatga gttccaactg cagctcagcc ccaagacttt tgcttcaaag     6240

acgtatggtc tgtgtgggat ctgtgatgag aacggagcca atgacttcat gctgagggat     6300

ggcacagtca ccacagactg gaaaacactt gttcaggaat ggactgtgca gcggccaggg     6360

cagacgtgcc agcccatcct ggaggagcag tgtcttgtcc ccgacagctc ccactgccag     6420

gtcctcctct taccactgtt tgctgaatgc cacaaggtcc tggctccagc cacattctat     6480

gccatctgcc agcaggacag ttgccaccag gagcaagtgt gtgaggtgat cgcctcttat     6540

gcccacctct gtcggaccaa cggggtctgc gttgactgga ggacacctga tttctgtgct     6600

atgtcatgcc caccatctct ggtttataac cactgtgagc atggctgtcc ccggcactgt     6660

gatggcaacg tgagctcctg tggggaccat ccctccgaag gctgtttctg ccctccagat     6720

aaagtcatgt tggaaggcag ctgtgtccct gaagaggcct gcactcagtg cattggtgag     6780

gatggagtcc agcaccagtt cctggaagcc tgggtcccgg accaccagcc ctgtcagatc     6840

tgcacatgcc tcagcgggcg gaaggtcaac tgcacaacgc agccctgccc cacggccaaa     6900

gctcccacgt gtggcctgtg tgaagtagcc cgcctccgcc agaatgcaga ccagtgctgc     6960

cccgagtatg agtgtgtgtg tgacccagtg agctgtgacc tgcccccagt gcctcactgt     7020

gaacgtggcc tccagcccac actgaccaac cctggcgagt gcagacccaa cttcacctgc     7080

gcctgcagga aggaggagtg caaaagagtg tccccaccct cctgcccccc gcaccgtttg     7140

cccacccttc ggaagaccca gtgctgtgat gagtatgagt gtgcctgcaa ctgtgtcaac     7200

tccacagtga gctgtcccct tgggtacttg gcctcaaccg ccaccaatga ctgtggctgt     7260

accacaacca cctgccttcc cgacaaggtg tgtgtccacc gaagcaccat ctaccctgtg     7320

ggccagttct gggaggaggg ctgcgatgtg tgcacctgca ccgacatgga ggatgccgtg     7380

atgggcctcc gcgtggccca gtgctcccag aagccctgtg aggacagctg tcggtcgggc     7440

ttcacttacg ttctgcatga aggcgagtgc tgtggaaggt gcctgccatc tgcctgtgag     7500

gtggtgactg gctcaccgcg gggggactcc cagtcttcct ggaagagtgt cggctcccag     7560

tgggcctccc cggagaaccc ctgcctcatc aatgagtgtg tccgagtgaa ggaggaggtc     7620

tttatacaac aaaggaacgt ctcctgcccc cagctggagg tccctgtctg cccctcgggc     7680

tttcagctga gctgtaagac ctcagcgtgc tgcccaagct gtcgctgtga gcgcatggag     7740

gcctgcatgc tcaatggcac tgtcattggg cccgggaaga ctgtgatgat cgatgtgtgc     7800

acgacctgcc gctgcatggt gcaggtgggg gtcatctctg gattcaagct ggagtgcagg     7860

aagaccacct gcaacccctg ccccctgggt tacaaggaag aaaataacac aggtgaatgt     7920

tgtgggagat gtttgcctac ggcttgcacc attcagctaa gaggaggaca gatcatgaca     7980

ctgaagcgtg atgagacgct ccaggatggc tgtgatactc acttctgcaa ggtcaatgag     8040

agaggagagt acttctggga gaagagggtc acaggctgcc caccctttga tgaacacaag     8100

tgtctggctg agggaggtaa aattatgaaa attccaggca cctgctgtga cacatgtgag     8160

gagcctgagt gcaacgacat cactgccagg ctgcagtatg tcaaggtggg aagctgtaag     8220

tctgaagtag aggtggatat ccactactgc cagggcaaat gtgccagcaa agccatgtac     8280

tccattgaca tcaacgatgt gcaggaccag tgctcctgct gctctccgac acggacggag     8340

cccatgcagg tggccctgca ctgcaccaat ggctctgttg tgtaccatga ggttctcaat     8400

gccatggagt gcaaatgctc ccccaggaag tgcagcaagt ga                        8442


<210>  2
<211>  2813
<212>  PRT
<213>  Homo sapiens

<400>  2

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


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


Ala Arg Cys Ser Leu Phe Gly Ser Asp Phe Val Asn Thr Phe Asp Gly 
        35                  40                  45              


Ser Met Tyr Ser Phe Ala Gly Tyr Cys Ser Tyr Leu Leu Ala Gly Gly 
    50                  55                  60                  


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


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


Phe Val Asn Gly Thr Val Thr Gln Gly Asp Gln Arg Val Ser Met Pro 
            100                 105                 110         


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


Leu Ser Gly Glu Ala Tyr Gly Phe Val Ala Arg Ile Asp Gly Ser Gly 
    130                 135                 140                 


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


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


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


Leu Ser Ser Gly Glu Gln Trp Cys Glu Arg Ala Ser Pro Pro Ser Ser 
        195                 200                 205             


Ser Cys Asn Ile Ser Ser Gly Glu Met Gln Lys Gly Leu Trp Glu Gln 
    210                 215                 220                 


Cys Gln Leu Leu Lys Ser Thr Ser Val Phe Ala Arg Cys His Pro Leu 
225                 230                 235                 240 


Val Asp Pro Glu Pro Phe Val Ala Leu Cys Glu Lys Thr Leu Cys Glu 
                245                 250                 255     


Cys Ala Gly Gly Leu Glu Cys Ala Cys Pro Ala Leu Leu Glu Tyr Ala 
            260                 265                 270         


Arg Thr Cys Ala Gln Glu Gly Met Val Leu Tyr Gly Trp Thr Asp His 
        275                 280                 285             


Ser Ala Cys Ser Pro Val Cys Pro Ala Gly Met Glu Tyr Arg Gln Cys 
    290                 295                 300                 


Val Ser Pro Cys Ala Arg Thr Cys Gln Ser Leu His Ile Asn Glu Met 
305                 310                 315                 320 


Cys Gln Glu Arg Cys Val Asp Gly Cys Ser Cys Pro Glu Gly Gln Leu 
                325                 330                 335     


Leu Asp Glu Gly Leu Cys Val Glu Ser Thr Glu Cys Pro Cys Val His 
            340                 345                 350         


Ser Gly Lys Arg Tyr Pro Pro Gly Thr Ser Leu Ser Arg Asp Cys Asn 
        355                 360                 365             


Thr Cys Ile Cys Arg Asn Ser Gln Trp Ile Cys Ser Asn Glu Glu Cys 
    370                 375                 380                 


Pro Gly Glu Cys Leu Val Thr Gly Gln Ser His Phe Lys Ser Phe Asp 
385                 390                 395                 400 


Asn Arg Tyr Phe Thr Phe Ser Gly Ile Cys Gln Tyr Leu Leu Ala Arg 
                405                 410                 415     


Asp Cys Gln Asp His Ser Phe Ser Ile Val Ile Glu Thr Val Gln Cys 
            420                 425                 430         


Ala Asp Asp Arg Asp Ala Val Cys Thr Arg Ser Val Thr Val Arg Leu 
        435                 440                 445             


Pro Gly Leu His Asn Ser Leu Val Lys Leu Lys His Gly Ala Gly Val 
    450                 455                 460                 


Ala Met Asp Gly Gln Asp Val Gln Leu Pro Leu Leu Lys Gly Asp Leu 
465                 470                 475                 480 


Arg Ile Gln His Thr Val Thr Ala Ser Val Arg Leu Ser Tyr Gly Glu 
                485                 490                 495     


Asp Leu Gln Met Asp Trp Asp Gly Arg Gly Arg Leu Leu Val Lys Leu 
            500                 505                 510         


Ser Pro Val Tyr Ala Gly Lys Thr Cys Gly Leu Cys Gly Asn Tyr Asn 
        515                 520                 525             


Gly Asn Gln Gly Asp Asp Phe Leu Thr Pro Ser Gly Leu Ala Glu Pro 
    530                 535                 540                 


Arg Val Glu Asp Phe Gly Asn Ala Trp Lys Leu His Gly Asp Cys Gln 
545                 550                 555                 560 


Asp Leu Gln Lys Gln His Ser Asp Pro Cys Ala Leu Asn Pro Arg Met 
                565                 570                 575     


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


Glu Ala Cys His Arg Ala Val Ser Pro Leu Pro Tyr Leu Arg Asn Cys 
        595                 600                 605             


Arg Tyr Asp Val Cys Ser Cys Ser Asp Gly Arg Glu Cys Leu Cys Gly 
    610                 615                 620                 


Ala Leu Ala Ser Tyr Ala Ala Ala Cys Ala Gly Arg Gly Val Arg Val 
625                 630                 635                 640 


Ala Trp Arg Glu Pro Gly Arg Cys Glu Leu Asn Cys Pro Lys Gly Gln 
                645                 650                 655     


Val Tyr Leu Gln Cys Gly Thr Pro Cys Asn Leu Thr Cys Arg Ser Leu 
            660                 665                 670         


Ser Tyr Pro Asp Glu Glu Cys Asn Glu Ala Cys Leu Glu Gly Cys Phe 
        675                 680                 685             


Cys Pro Pro Gly Leu Tyr Met Asp Glu Arg Gly Asp Cys Val Pro Lys 
    690                 695                 700                 


Ala Gln Cys Pro Cys Tyr Tyr Asp Gly Glu Ile Phe Gln Pro Glu Asp 
705                 710                 715                 720 


Ile Phe Ser Asp His His Thr Met Cys Tyr Cys Glu Asp Gly Phe Met 
                725                 730                 735     


His Cys Thr Met Ser Gly Val Pro Gly Ser Leu Leu Pro Asp Ala Val 
            740                 745                 750         


Leu Ser Ser Pro Leu Ser His Arg Ser Lys Arg Ser Leu Ser Cys Arg 
        755                 760                 765             


Pro Pro Met Val Lys Leu Val Cys Pro Ala Asp Asn Leu Arg Ala Glu 
    770                 775                 780                 


Gly Leu Glu Cys Thr Lys Thr Cys Gln Asn Tyr Asp Leu Glu Cys Met 
785                 790                 795                 800 


Ser Met Gly Cys Val Ser Gly Cys Leu Cys Pro Pro Gly Met Val Arg 
                805                 810                 815     


His Glu Asn Arg Cys Val Ala Leu Glu Arg Cys Pro Cys Phe His Gln 
            820                 825                 830         


Gly Lys Glu Tyr Ala Pro Gly Glu Thr Val Lys Ile Gly Cys Asn Thr 
        835                 840                 845             


Cys Val Cys Arg Asp Arg Lys Trp Asn Cys Thr Asp His Val Cys Asp 
    850                 855                 860                 


Ala Thr Cys Ser Thr Ile Gly Met Ala His Tyr Leu Thr Phe Asp Gly 
865                 870                 875                 880 


Leu Lys Tyr Leu Phe Pro Gly Glu Cys Gln Tyr Val Leu Val Gln Asp 
                885                 890                 895     


Tyr Cys Gly Ser Asn Pro Gly Thr Phe Arg Ile Leu Val Gly Asn Lys 
            900                 905                 910         


Gly Cys Ser His Pro Ser Val Lys Cys Lys Lys Arg Val Thr Ile Leu 
        915                 920                 925             


Val Glu Gly Gly Glu Ile Glu Leu Phe Asp Gly Glu Val Asn Val Lys 
    930                 935                 940                 


Arg Pro Met Lys Asp Glu Thr His Phe Glu Val Val Glu Ser Gly Arg 
945                 950                 955                 960 


Tyr Ile Ile Leu Leu Leu Gly Lys Ala Leu Ser Val Val Trp Asp Arg 
                965                 970                 975     


His Leu Ser Ile Ser Val Val Leu Lys Gln Thr Tyr Gln Glu Lys Val 
            980                 985                 990         


Cys Gly Leu Cys Gly Asn Phe Asp  Gly Ile Gln Asn Asn  Asp Leu Thr 
        995                 1000                 1005             


Ser Ser  Asn Leu Gln Val Glu  Glu Asp Pro Val Asp  Phe Gly Asn 
    1010                 1015                 1020             


Ser Trp  Lys Val Ser Ser Gln  Cys Ala Asp Thr Arg  Lys Val Pro 
    1025                 1030                 1035             


Leu Asp  Ser Ser Pro Ala Thr  Cys His Asn Asn Ile  Met Lys Gln 
    1040                 1045                 1050             


Thr Met  Val Asp Ser Ser Cys  Arg Ile Leu Thr Ser  Asp Val Phe 
    1055                 1060                 1065             


Gln Asp  Cys Asn Lys Leu Val  Asp Pro Glu Pro Tyr  Leu Asp Val 
    1070                 1075                 1080             


Cys Ile  Tyr Asp Thr Cys Ser  Cys Glu Ser Ile Gly  Asp Cys Ala 
    1085                 1090                 1095             


Cys Phe  Cys Asp Thr Ile Ala  Ala Tyr Ala His Val  Cys Ala Gln 
    1100                 1105                 1110             


His Gly  Lys Val Val Thr Trp  Arg Thr Ala Thr Leu  Cys Pro Gln 
    1115                 1120                 1125             


Ser Cys  Glu Glu Arg Asn Leu  Arg Glu Asn Gly Tyr  Glu Cys Glu 
    1130                 1135                 1140             


Trp Arg  Tyr Asn Ser Cys Ala  Pro Ala Cys Gln Val  Thr Cys Gln 
    1145                 1150                 1155             


His Pro  Glu Pro Leu Ala Cys  Pro Val Gln Cys Val  Glu Gly Cys 
    1160                 1165                 1170             


His Ala  His Cys Pro Pro Gly  Lys Ile Leu Asp Glu  Leu Leu Gln 
    1175                 1180                 1185             


Thr Cys  Val Asp Pro Glu Asp  Cys Pro Val Cys Glu  Val Ala Gly 
    1190                 1195                 1200             


Arg Arg  Phe Ala Ser Gly Lys  Lys Val Thr Leu Asn  Pro Ser Asp 
    1205                 1210                 1215             


Pro Glu  His Cys Gln Ile Cys  His Cys Asp Val Val  Asn Leu Thr 
    1220                 1225                 1230             


Cys Glu  Ala Cys Gln Glu Pro  Gly Gly Leu Val Val  Pro Pro Thr 
    1235                 1240                 1245             


Asp Ala  Pro Val Ser Pro Thr  Thr Leu Tyr Val Glu  Asp Ile Ser 
    1250                 1255                 1260             


Glu Pro  Pro Leu His Asp Phe  Tyr Cys Ser Arg Leu  Leu Asp Leu 
    1265                 1270                 1275             


Val Phe  Leu Leu Asp Gly Ser  Ser Arg Leu Ser Glu  Ala Glu Phe 
    1280                 1285                 1290             


Glu Val  Leu Lys Ala Phe Val  Val Asp Met Met Glu  Arg Leu Arg 
    1295                 1300                 1305             


Ile Ser  Gln Lys Trp Val Arg  Val Ala Val Val Glu  Tyr His Asp 
    1310                 1315                 1320             


Gly Ser  His Ala Tyr Ile Gly  Leu Lys Asp Arg Lys  Arg Pro Ser 
    1325                 1330                 1335             


Glu Leu  Arg Arg Ile Ala Ser  Gln Val Lys Tyr Ala  Gly Ser Gln 
    1340                 1345                 1350             


Val Ala  Ser Thr Ser Glu Val  Leu Lys Tyr Thr Leu  Phe Gln Ile 
    1355                 1360                 1365             


Phe Ser  Lys Ile Asp Arg Pro  Glu Ala Ser Arg Ile  Thr Leu Leu 
    1370                 1375                 1380             


Leu Met  Ala Ser Gln Glu Pro  Gln Arg Met Ser Arg  Asn Phe Val 
    1385                 1390                 1395             


Arg Tyr  Val Gln Gly Leu Lys  Lys Lys Lys Val Ile  Val Ile Pro 
    1400                 1405                 1410             


Val Gly  Ile Gly Pro His Ala  Asn Leu Lys Gln Ile  Arg Leu Ile 
    1415                 1420                 1425             


Glu Lys  Gln Ala Pro Glu Asn  Lys Ala Phe Val Leu  Ser Ser Val 
    1430                 1435                 1440             


Asp Glu  Leu Glu Gln Gln Arg  Asp Glu Ile Val Ser  Tyr Leu Cys 
    1445                 1450                 1455             


Asp Leu  Ala Pro Glu Ala Pro  Pro Pro Thr Leu Pro  Pro Asp Met 
    1460                 1465                 1470             


Ala Gln  Val Thr Val Gly Pro  Gly Leu Leu Gly Val  Ser Thr Leu 
    1475                 1480                 1485             


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


Glu Gly  Ser Asp Lys Ile Gly  Glu Ala Asp Phe Asn  Arg Ser Lys 
    1505                 1510                 1515             


Glu Phe  Met Glu Glu Val Ile  Gln Arg Met Asp Val  Gly Gln Asp 
    1520                 1525                 1530             


Ser Ile  His Val Thr Val Leu  Gln Tyr Ser Tyr Met  Val Thr Val 
    1535                 1540                 1545             


Glu Tyr  Pro Phe Ser Glu Ala  Gln Ser Lys Gly Asp  Ile Leu Gln 
    1550                 1555                 1560             


Arg Val  Arg Glu Ile Arg Tyr  Gln Gly Gly Asn Arg  Thr Asn Thr 
    1565                 1570                 1575             


Gly Leu  Ala Leu Arg Tyr Leu  Ser Asp His Ser Phe  Leu Val Ser 
    1580                 1585                 1590             


Gln Gly  Asp Arg Glu Gln Ala  Pro Asn Leu Val Tyr  Met Val Thr 
    1595                 1600                 1605             


Gly Asn  Pro Ala Ser Asp Glu  Ile Lys Arg Leu Pro  Gly Asp Ile 
    1610                 1615                 1620             


Gln Val  Val Pro Ile Gly Val  Gly Pro Asn Ala Asn  Val Gln Glu 
    1625                 1630                 1635             


Leu Glu  Arg Ile Gly Trp Pro  Asn Ala Pro Ile Leu  Ile Gln Asp 
    1640                 1645                 1650             


Phe Glu  Thr Leu Pro Arg Glu  Ala Pro Asp Leu Val  Leu Gln Arg 
    1655                 1660                 1665             


Cys Cys  Ser Gly Glu Gly Leu  Gln Ile Pro Thr Leu  Ser Pro Ala 
    1670                 1675                 1680             


Pro Asp  Cys Ser Gln Pro Leu  Asp Val Ile Leu Leu  Leu Asp Gly 
    1685                 1690                 1695             


Ser Ser  Ser Phe Pro Ala Ser  Tyr Phe Asp Glu Met  Lys Ser Phe 
    1700                 1705                 1710             


Ala Lys  Ala Phe Ile Ser Lys  Ala Asn Ile Gly Pro  Arg Leu Thr 
    1715                 1720                 1725             


Gln Val  Ser Val Leu Gln Tyr  Gly Ser Ile Thr Thr  Ile Asp Val 
    1730                 1735                 1740             


Pro Trp  Asn Val Val Pro Glu  Lys Ala His Leu Leu  Ser Leu Val 
    1745                 1750                 1755             


Asp Val  Met Gln Arg Glu Gly  Gly Pro Ser Gln Ile  Gly Asp Ala 
    1760                 1765                 1770             


Leu Gly  Phe Ala Val Arg Tyr  Leu Thr Ser Glu Met  His Gly Ala 
    1775                 1780                 1785             


Arg Pro  Gly Ala Ser Lys Ala  Val Val Ile Leu Val  Thr Asp Val 
    1790                 1795                 1800             


Ser Val  Asp Ser Val Asp Ala  Ala Ala Asp Ala Ala  Arg Ser Asn 
    1805                 1810                 1815             


Arg Val  Thr Val Phe Pro Ile  Gly Ile Gly Asp Arg  Tyr Asp Ala 
    1820                 1825                 1830             


Ala Gln  Leu Arg Ile Leu Ala  Gly Pro Ala Gly Asp  Ser Asn Val 
    1835                 1840                 1845             


Val Lys  Leu Gln Arg Ile Glu  Asp Leu Pro Thr Met  Val Thr Leu 
    1850                 1855                 1860             


Gly Asn  Ser Phe Leu His Lys  Leu Cys Ser Gly Phe  Val Arg Ile 
    1865                 1870                 1875             


Cys Met  Asp Glu Asp Gly Asn  Glu Lys Arg Pro Gly  Asp Val Trp 
    1880                 1885                 1890             


Thr Leu  Pro Asp Gln Cys His  Thr Val Thr Cys Gln  Pro Asp Gly 
    1895                 1900                 1905             


Gln Thr  Leu Leu Lys Ser His  Arg Val Asn Cys Asp  Arg Gly Leu 
    1910                 1915                 1920             


Arg Pro  Ser Cys Pro Asn Ser  Gln Ser Pro Val Lys  Val Glu Glu 
    1925                 1930                 1935             


Thr Cys  Gly Cys Arg Trp Thr  Cys Pro Cys Val Cys  Thr Gly Ser 
    1940                 1945                 1950             


Ser Thr  Arg His Ile Val Thr  Phe Asp Gly Gln Asn  Phe Lys Leu 
    1955                 1960                 1965             


Thr Gly  Ser Cys Ser Tyr Val  Leu Phe Gln Asn Lys  Glu Gln Asp 
    1970                 1975                 1980             


Leu Glu  Val Ile Leu His Asn  Gly Ala Cys Ser Pro  Gly Ala Arg 
    1985                 1990                 1995             


Gln Gly  Cys Met Lys Ser Ile  Glu Val Lys His Ser  Ala Leu Ser 
    2000                 2005                 2010             


Val Glu  Leu His Ser Asp Met  Glu Val Thr Val Asn  Gly Arg Leu 
    2015                 2020                 2025             


Val Ser  Val Pro Tyr Val Gly  Gly Asn Met Glu Val  Asn Val Tyr 
    2030                 2035                 2040             


Gly Ala  Ile Met His Glu Val  Arg Phe Asn His Leu  Gly His Ile 
    2045                 2050                 2055             


Phe Thr  Phe Thr Pro Gln Asn  Asn Glu Phe Gln Leu  Gln Leu Ser 
    2060                 2065                 2070             


Pro Lys  Thr Phe Ala Ser Lys  Thr Tyr Gly Leu Cys  Gly Ile Cys 
    2075                 2080                 2085             


Asp Glu  Asn Gly Ala Asn Asp  Phe Met Leu Arg Asp  Gly Thr Val 
    2090                 2095                 2100             


Thr Thr  Asp Trp Lys Thr Leu  Val Gln Glu Trp Thr  Val Gln Arg 
    2105                 2110                 2115             


Pro Gly  Gln Thr Cys Gln Pro  Ile Leu Glu Glu Gln  Cys Leu Val 
    2120                 2125                 2130             


Pro Asp  Ser Ser His Cys Gln  Val Leu Leu Leu Pro  Leu Phe Ala 
    2135                 2140                 2145             


Glu Cys  His Lys Val Leu Ala  Pro Ala Thr Phe Tyr  Ala Ile Cys 
    2150                 2155                 2160             


Gln Gln  Asp Ser Cys His Gln  Glu Gln Val Cys Glu  Val Ile Ala 
    2165                 2170                 2175             


Ser Tyr  Ala His Leu Cys Arg  Thr Asn Gly Val Cys  Val Asp Trp 
    2180                 2185                 2190             


Arg Thr  Pro Asp Phe Cys Ala  Met Ser Cys Pro Pro  Ser Leu Val 
    2195                 2200                 2205             


Tyr Asn  His Cys Glu His Gly  Cys Pro Arg His Cys  Asp Gly Asn 
    2210                 2215                 2220             


Val Ser  Ser Cys Gly Asp His  Pro Ser Glu Gly Cys  Phe Cys Pro 
    2225                 2230                 2235             


Pro Asp  Lys Val Met Leu Glu  Gly Ser Cys Val Pro  Glu Glu Ala 
    2240                 2245                 2250             


Cys Thr  Gln Cys Ile Gly Glu  Asp Gly Val Gln His  Gln Phe Leu 
    2255                 2260                 2265             


Glu Ala  Trp Val Pro Asp His  Gln Pro Cys Gln Ile  Cys Thr Cys 
    2270                 2275                 2280             


Leu Ser  Gly Arg Lys Val Asn  Cys Thr Thr Gln Pro  Cys Pro Thr 
    2285                 2290                 2295             


Ala Lys  Ala Pro Thr Cys Gly  Leu Cys Glu Val Ala  Arg Leu Arg 
    2300                 2305                 2310             


Gln Asn  Ala Asp Gln Cys Cys  Pro Glu Tyr Glu Cys  Val Cys Asp 
    2315                 2320                 2325             


Pro Val  Ser Cys Asp Leu Pro  Pro Val Pro His Cys  Glu Arg Gly 
    2330                 2335                 2340             


Leu Gln  Pro Thr Leu Thr Asn  Pro Gly Glu Cys Arg  Pro Asn Phe 
    2345                 2350                 2355             


Thr Cys  Ala Cys Arg Lys Glu  Glu Cys Lys Arg Val  Ser Pro Pro 
    2360                 2365                 2370             


Ser Cys  Pro Pro His Arg Leu  Pro Thr Leu Arg Lys  Thr Gln Cys 
    2375                 2380                 2385             


Cys Asp  Glu Tyr Glu Cys Ala  Cys Asn Cys Val Asn  Ser Thr Val 
    2390                 2395                 2400             


Ser Cys  Pro Leu Gly Tyr Leu  Ala Ser Thr Ala Thr  Asn Asp Cys 
    2405                 2410                 2415             


Gly Cys  Thr Thr Thr Thr Cys  Leu Pro Asp Lys Val  Cys Val His 
    2420                 2425                 2430             


Arg Ser  Thr Ile Tyr Pro Val  Gly Gln Phe Trp Glu  Glu Gly Cys 
    2435                 2440                 2445             


Asp Val  Cys Thr Cys Thr Asp  Met Glu Asp Ala Val  Met Gly Leu 
    2450                 2455                 2460             


Arg Val  Ala Gln Cys Ser Gln  Lys Pro Cys Glu Asp  Ser Cys Arg 
    2465                 2470                 2475             


Ser Gly  Phe Thr Tyr Val Leu  His Glu Gly Glu Cys  Cys Gly Arg 
    2480                 2485                 2490             


Cys Leu  Pro Ser Ala Cys Glu  Val Val Thr Gly Ser  Pro Arg Gly 
    2495                 2500                 2505             


Asp Ser  Gln Ser Ser Trp Lys  Ser Val Gly Ser Gln  Trp Ala Ser 
    2510                 2515                 2520             


Pro Glu  Asn Pro Cys Leu Ile  Asn Glu Cys Val Arg  Val Lys Glu 
    2525                 2530                 2535             


Glu Val  Phe Ile Gln Gln Arg  Asn Val Ser Cys Pro  Gln Leu Glu 
    2540                 2545                 2550             


Val Pro  Val Cys Pro Ser Gly  Phe Gln Leu Ser Cys  Lys Thr Ser 
    2555                 2560                 2565             


Ala Cys  Cys Pro Ser Cys Arg  Cys Glu Arg Met Glu  Ala Cys Met 
    2570                 2575                 2580             


Leu Asn  Gly Thr Val Ile Gly  Pro Gly Lys Thr Val  Met Ile Asp 
    2585                 2590                 2595             


Val Cys  Thr Thr Cys Arg Cys  Met Val Gln Val Gly  Val Ile Ser 
    2600                 2605                 2610             


Gly Phe  Lys Leu Glu Cys Arg  Lys Thr Thr Cys Asn  Pro Cys Pro 
    2615                 2620                 2625             


Leu Gly  Tyr Lys Glu Glu Asn  Asn Thr Gly Glu Cys  Cys Gly Arg 
    2630                 2635                 2640             


Cys Leu  Pro Thr Ala Cys Thr  Ile Gln Leu Arg Gly  Gly Gln Ile 
    2645                 2650                 2655             


Met Thr  Leu Lys Arg Asp Glu  Thr Leu Gln Asp Gly  Cys Asp Thr 
    2660                 2665                 2670             


His Phe  Cys Lys Val Asn Glu  Arg Gly Glu Tyr Phe  Trp Glu Lys 
    2675                 2680                 2685             


Arg Val  Thr Gly Cys Pro Pro  Phe Asp Glu His Lys  Cys Leu Ala 
    2690                 2695                 2700             


Glu Gly  Gly Lys Ile Met Lys  Ile Pro Gly Thr Cys  Cys Asp Thr 
    2705                 2710                 2715             


Cys Glu  Glu Pro Glu Cys Asn  Asp Ile Thr Ala Arg  Leu Gln Tyr 
    2720                 2725                 2730             


Val Lys  Val Gly Ser Cys Lys  Ser Glu Val Glu Val  Asp Ile His 
    2735                 2740                 2745             


Tyr Cys  Gln Gly Lys Cys Ala  Ser Lys Ala Met Tyr  Ser Ile Asp 
    2750                 2755                 2760             


Ile Asn  Asp Val Gln Asp Gln  Cys Ser Cys Cys Ser  Pro Thr Arg 
    2765                 2770                 2775             


Thr Glu  Pro Met Gln Val Ala  Leu His Cys Thr Asn  Gly Ser Val 
    2780                 2785                 2790             


Val Tyr  His Glu Val Leu Asn  Ala Met Glu Cys Lys  Cys Ser Pro 
    2795                 2800                 2805             


Arg Lys  Cys Ser Lys 
    2810             


<210>  3
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer VWF+

<400>  3
ttcgaattcc cgcagccctc atttgcaggg                                        30


<210>  4
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer VWF-

<400>  4
tccgaattcc ggcagcagca ggcacccatg c                                      31


<210>  5
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4070

<400>  5
ggtgtgtccc gctaacaacc tgcgggctg                                         29


<210>  6
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4071

<400>  6
cagcccgcag gttgttagcg ggacacacc                                         29


<210>  7
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Pirmer We4072

<400>  7
gtcccgctga caaccctcgg gctgaaggg                                         29


<210>  8
<211>  29
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4073

<400>  8
cccttcagcc cgagggttgt cagcgggac                                         29


<210>  9
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4074

<400>  9
ctgaagggct cgagtgtgcc aaaacgtgcc agaac                                  35


<210>  10
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4075

<400>  10
gttctggcac gttttggcac actcgagccc ttcag                                  35


<210>  11
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4076

<400>  11
gtgtaccaaa acgtgccgga actatgacct ggagtgc                                37


<210>  12
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4077

<400>  12
gcactccagg tcatagttcc ggcacgtttt ggtacac                                37


<210>  13
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4078

<400>  13
gtaccaaaac gtgccagaag tatgacctgg agtgc                                  35


<210>  14
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  We4079

<400>  14
gcactccagg tcatacttct ggcacgtttt ggtac                                  35


<210>  15
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4080

<400>  15
ctggagtgca tgagcagggg ctgtgtctct ggctg                                  35


<210>  16
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4081

<400>  16
cagccagaga cacagcccct gctcatgcac tccag                                  35


<210>  17
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4082

<400>  17
ctggagtgca tgagcaaggg ctgtgtctct ggctg                                  35


<210>  18
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4083

<400>  18
cagccagaga cacagccctt gctcatgcac tccag                                  35


<210>  19
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4084

<400>  19
catggtccgg catgccaaca gatgtgtggc cctg                                   34


<210>  20
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4085

<400>  20
cagggccaca catctgttgg catgccggac catg                                   34


<210>  21
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4086

<400>  21
catggtccgg cataagaaca gatgtgtggc cctg                                   34


<210>  22
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4087

<400>  22
cagggccaca catctgttct tatgccggac catg                                   34


<210>  23
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4088

<400>  23
ggtccggcat gagaagagat gtgtggccct g                                      31


<210>  24
<211>  31
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4089

<400>  24
cagggccaca catctcttct catgccggac c                                      31


<210>  25
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4090

<400>  25
gcttccatca gggcaagcag tatgcccctg gagaaac                                37


<210>  26
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4091

<400>  26
gtttctccag gggcatactg cttgccctga tggaagc                                37


<210>  27
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4092

<400>  27
gggcaaggag tatgccaagg gagaaacagt gaagattgg                              39


<210>  28
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4093

<400>  28
ccaatcttca ctgtttctcc cttggcatac tccttgccc                              39


<210>  29
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4094

<400>  29
cggaaccgga agtggaactg cacagaccat gtgtg                                  35


<210>  30
<211>  35
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer We4095

<400>  30
cacacatggt ctgtgcagtt ccacttccgg ttccg                                  35


<210>  31
<211>  102
<212>  PRT
<213>  Homo sapiens

<400>  31

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 
            100         


<210>  32
<211>  2050
<212>  PRT
<213>  Homo sapiens

<400>  32

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 


<210>  33
<211>  102
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Modified D' domain of VWF


<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa is Leu or Pro

<220>
<221>  MISC_FEATURE
<222>  (24)..(24)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (26)..(26)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (31)..(31)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (33)..(33)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (35)..(35)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (39)..(39)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (55)..(55)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (56)..(56)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (62)..(62)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (72)..(72)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (75)..(75)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (90)..(90)
<223>  Xaa is any amino acid

<400>  33

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


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


Xaa Leu Xaa Cys Met Ser Xaa Gly Cys Val Ser Gly Cys Leu Cys Pro 
        35                  40                  45              


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


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


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


Asp His Val Cys Asp Ala 
            100         


<210>  34
<211>  102
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified D' domain


<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (26)..(26)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (31)..(31)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (39)..(39)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (55)..(55)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (56)..(56)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (72)..(72)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (75)..(75)
<223>  Xaa is any amino acid

<220>
<221>  MISC_FEATURE
<222>  (90)..(90)
<223>  Xaa is any amino acid

<400>  34

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


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


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


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


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


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


Asp His Val Cys Asp Ala 
            100         


<210>  35
<211>  102
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified D' domain


<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa is Asp or Asn

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa is Leu or Pro

<220>
<221>  MISC_FEATURE
<222>  (26)..(26)
<223>  Xaa is Thr or Ala

<220>
<221>  MISC_FEATURE
<222>  (30)..(30)
<223>  Xaa is Gln or Arg

<220>
<221>  MISC_FEATURE
<222>  (31)..(31)
<223>  Xaa is Asn or Lys

<220>
<221>  MISC_FEATURE
<222>  (39)..(39)
<223>  Xaa is Met or Arg or Lys

<220>
<221>  MISC_FEATURE
<222>  (55)..(55)
<223>  Xaa Glu or Ala or Lys

<220>
<221>  MISC_FEATURE
<222>  (56)..(56)
<223>  Xaa Asn or Lys

<220>
<221>  MISC_FEATURE
<222>  (72)..(72)
<223>  Xaa Glu or Gln

<220>
<221>  MISC_FEATURE
<222>  (75)..(75)
<223>  Xaa Pro or Lys

<220>
<221>  MISC_FEATURE
<222>  (90)..(90)
<223>  Xaa Asp or Asn

<400>  35

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


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


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


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


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


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


Asp His Val Cys Asp Ala 
            100         


<210>  36
<211>  2332
<212>  PRT
<213>  Homo sapiens

<400>  36

Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser Trp Asp Tyr 
1               5                   10                  15      


Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg Phe Pro Pro 
            20                  25                  30          


Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys 
        35                  40                  45              


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


Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val 
65                  70                  75                  80  


Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
                85                  90                  95      


Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala 
            100                 105                 110         


Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val 
        115                 120                 125             


Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn 
    130                 135                 140                 


Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser 
145                 150                 155                 160 


His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
                165                 170                 175     


Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr Gln Thr Leu 
            180                 185                 190         


His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp 
        195                 200                 205             


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


Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr Val Asn Arg 
225                 230                 235                 240 


Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val Tyr Trp His 
                245                 250                 255     


Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu 
            260                 265                 270         


Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile 
        275                 280                 285             


Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly 
    290                 295                 300                 


Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His Asp Gly Met 
305                 310                 315                 320 


Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg 
                325                 330                 335     


Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp 
            340                 345                 350         


Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe 
        355                 360                 365             


Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr Trp Val His 
    370                 375                 380                 


Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu 
385                 390                 395                 400 


Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro 
                405                 410                 415     


Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr 
            420                 425                 430         


Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile 
        435                 440                 445             


Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile 
    450                 455                 460                 


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile 
465                 470                 475                 480 


Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys 
                485                 490                 495     


His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys 
            500                 505                 510         


Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys 
        515                 520                 525             


Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg Asp Leu Ala 
    530                 535                 540                 


Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp 
545                 550                 555                 560 


Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe 
                565                 570                 575     


Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln 
            580                 585                 590         


Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe 
        595                 600                 605             


Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser 
    610                 615                 620                 


Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu 
625                 630                 635                 640 


Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr 
                645                 650                 655     


Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr Leu Phe Pro 
            660                 665                 670         


Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp 
        675                 680                 685             


Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala 
    690                 695                 700                 


Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu 
705                 710                 715                 720 


Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala 
                725                 730                 735     


Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Arg Ser Thr Arg 
            740                 745                 750         


Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp Ile Glu Lys 
        755                 760                 765             


Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys Ile Gln Asn 
    770                 775                 780                 


Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser Pro Thr Pro 
785                 790                 795                 800 


His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr Glu Thr Phe 
                805                 810                 815     


Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn Ser Leu Ser 
            820                 825                 830         


Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly Asp Met Val 
        835                 840                 845             


Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu Lys Leu Gly 
    850                 855                 860                 


Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys Val Ser Ser 
865                 870                 875                 880 


Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn Leu Ala Ala 
                885                 890                 895     


Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met Pro Val His 
            900                 905                 910         


Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys Ser Ser Pro 
        915                 920                 925             


Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu Asn Asn Asp 
    930                 935                 940                 


Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu Ser Ser Trp 
945                 950                 955                 960 


Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe Lys Gly Lys 
                965                 970                 975     


Arg Ala His Gly Pro Ala Leu Leu Thr Lys Asp Asn Ala Leu Phe Lys 
            980                 985                 990         


Val Ser Ile Ser Leu Leu Lys Thr  Asn Lys Thr Ser Asn  Asn Ser Ala 
        995                 1000                 1005             


Thr Asn  Arg Lys Thr His Ile  Asp Gly Pro Ser Leu  Leu Ile Glu 
    1010                 1015                 1020             


Asn Ser  Pro Ser Val Trp Gln  Asn Ile Leu Glu Ser  Asp Thr Glu 
    1025                 1030                 1035             


Phe Lys  Lys Val Thr Pro Leu  Ile His Asp Arg Met  Leu Met Asp 
    1040                 1045                 1050             


Lys Asn  Ala Thr Ala Leu Arg  Leu Asn His Met Ser  Asn Lys Thr 
    1055                 1060                 1065             


Thr Ser  Ser Lys Asn Met Glu  Met Val Gln Gln Lys  Lys Glu Gly 
    1070                 1075                 1080             


Pro Ile  Pro Pro Asp Ala Gln  Asn Pro Asp Met Ser  Phe Phe Lys 
    1085                 1090                 1095             


Met Leu  Phe Leu Pro Glu Ser  Ala Arg Trp Ile Gln  Arg Thr His 
    1100                 1105                 1110             


Gly Lys  Asn Ser Leu Asn Ser  Gly Gln Gly Pro Ser  Pro Lys Gln 
    1115                 1120                 1125             


Leu Val  Ser Leu Gly Pro Glu  Lys Ser Val Glu Gly  Gln Asn Phe 
    1130                 1135                 1140             


Leu Ser  Glu Lys Asn Lys Val  Val Val Gly Lys Gly  Glu Phe Thr 
    1145                 1150                 1155             


Lys Asp  Val Gly Leu Lys Glu  Met Val Phe Pro Ser  Ser Arg Asn 
    1160                 1165                 1170             


Leu Phe  Leu Thr Asn Leu Asp  Asn Leu His Glu Asn  Asn Thr His 
    1175                 1180                 1185             


Asn Gln  Glu Lys Lys Ile Gln  Glu Glu Ile Glu Lys  Lys Glu Thr 
    1190                 1195                 1200             


Leu Ile  Gln Glu Asn Val Val  Leu Pro Gln Ile His  Thr Val Thr 
    1205                 1210                 1215             


Gly Thr  Lys Asn Phe Met Lys  Asn Leu Phe Leu Leu  Ser Thr Arg 
    1220                 1225                 1230             


Gln Asn  Val Glu Gly Ser Tyr  Asp Gly Ala Tyr Ala  Pro Val Leu 
    1235                 1240                 1245             


Gln Asp  Phe Arg Ser Leu Asn  Asp Ser Thr Asn Arg  Thr Lys Lys 
    1250                 1255                 1260             


His Thr  Ala His Phe Ser Lys  Lys Gly Glu Glu Glu  Asn Leu Glu 
    1265                 1270                 1275             


Gly Leu  Gly Asn Gln Thr Lys  Gln Ile Val Glu Lys  Tyr Ala Cys 
    1280                 1285                 1290             


Thr Thr  Arg Ile Ser Pro Asn  Thr Ser Gln Gln Asn  Phe Val Thr 
    1295                 1300                 1305             


Gln Arg  Ser Lys Arg Ala Leu  Lys Gln Phe Arg Leu  Pro Leu Glu 
    1310                 1315                 1320             


Glu Thr  Glu Leu Glu Lys Arg  Ile Ile Val Asp Asp  Thr Ser Thr 
    1325                 1330                 1335             


Gln Trp  Ser Lys Asn Met Lys  His Leu Thr Pro Ser  Thr Leu Thr 
    1340                 1345                 1350             


Gln Ile  Asp Tyr Asn Glu Lys  Glu Lys Gly Ala Ile  Thr Gln Ser 
    1355                 1360                 1365             


Pro Leu  Ser Asp Cys Leu Thr  Arg Ser His Ser Ile  Pro Gln Ala 
    1370                 1375                 1380             


Asn Arg  Ser Pro Leu Pro Ile  Ala Lys Val Ser Ser  Phe Pro Ser 
    1385                 1390                 1395             


Ile Arg  Pro Ile Tyr Leu Thr  Arg Val Leu Phe Gln  Asp Asn Ser 
    1400                 1405                 1410             


Ser His  Leu Pro Ala Ala Ser  Tyr Arg Lys Lys Asp  Ser Gly Val 
    1415                 1420                 1425             


Gln Glu  Ser Ser His Phe Leu  Gln Gly Ala Lys Lys  Asn Asn Leu 
    1430                 1435                 1440             


Ser Leu  Ala Ile Leu Thr Leu  Glu Met Thr Gly Asp  Gln Arg Glu 
    1445                 1450                 1455             


Val Gly  Ser Leu Gly Thr Ser  Ala Thr Asn Ser Val  Thr Tyr Lys 
    1460                 1465                 1470             


Lys Val  Glu Asn Thr Val Leu  Pro Lys Pro Asp Leu  Pro Lys Thr 
    1475                 1480                 1485             


Ser Gly  Lys Val Glu Leu Leu  Pro Lys Val His Ile  Tyr Gln Lys 
    1490                 1495                 1500             


Asp Leu  Phe Pro Thr Glu Thr  Ser Asn Gly Ser Pro  Gly His Leu 
    1505                 1510                 1515             


Asp Leu  Val Glu Gly Ser Leu  Leu Gln Gly Thr Glu  Gly Ala Ile 
    1520                 1525                 1530             


Lys Trp  Asn Glu Ala Asn Arg  Pro Gly Lys Val Pro  Phe Leu Arg 
    1535                 1540                 1545             


Val Ala  Thr Glu Ser Ser Ala  Lys Thr Pro Ser Lys  Leu Leu Asp 
    1550                 1555                 1560             


Pro Leu  Ala Trp Asp Asn His  Tyr Gly Thr Gln Ile  Pro Lys Glu 
    1565                 1570                 1575             


Glu Trp  Lys Ser Gln Glu Lys  Ser Pro Glu Lys Thr  Ala Phe Lys 
    1580                 1585                 1590             


Lys Lys  Asp Thr Ile Leu Ser  Leu Asn Ala Cys Glu  Ser Asn His 
    1595                 1600                 1605             


Ala Ile  Ala Ala Ile Asn Glu  Gly Gln Asn Lys Pro  Glu Ile Glu 
    1610                 1615                 1620             


Val Thr  Trp Ala Lys Gln Gly  Arg Thr Glu Arg Leu  Cys Ser Gln 
    1625                 1630                 1635             


Asn Pro  Pro Val Leu Lys Arg  His Gln Arg Glu Ile  Thr Arg Thr 
    1640                 1645                 1650             


Thr Leu  Gln Ser Asp Gln Glu  Glu Ile Asp Tyr Asp  Asp Thr Ile 
    1655                 1660                 1665             


Ser Val  Glu Met Lys Lys Glu  Asp Phe Asp Ile Tyr  Asp Glu Asp 
    1670                 1675                 1680             


Glu Asn  Gln Ser Pro Arg Ser  Phe Gln Lys Lys Thr  Arg His Tyr 
    1685                 1690                 1695             


Phe Ile  Ala Ala Val Glu Arg  Leu Trp Asp Tyr Gly  Met Ser Ser 
    1700                 1705                 1710             


Ser Pro  His Val Leu Arg Asn  Arg Ala Gln Ser Gly  Ser Val Pro 
    1715                 1720                 1725             


Gln Phe  Lys Lys Val Val Phe  Gln Glu Phe Thr Asp  Gly Ser Phe 
    1730                 1735                 1740             


Thr Gln  Pro Leu Tyr Arg Gly  Glu Leu Asn Glu His  Leu Gly Leu 
    1745                 1750                 1755             


Leu Gly  Pro Tyr Ile Arg Ala  Glu Val Glu Asp Asn  Ile Met Val 
    1760                 1765                 1770             


Thr Phe  Arg Asn Gln Ala Ser  Arg Pro Tyr Ser Phe  Tyr Ser Ser 
    1775                 1780                 1785             


Leu Ile  Ser Tyr Glu Glu Asp  Gln Arg Gln Gly Ala  Glu Pro Arg 
    1790                 1795                 1800             


Lys Asn  Phe Val Lys Pro Asn  Glu Thr Lys Thr Tyr  Phe Trp Lys 
    1805                 1810                 1815             


Val Gln  His His Met Ala Pro  Thr Lys Asp Glu Phe  Asp Cys Lys 
    1820                 1825                 1830             


Ala Trp  Ala Tyr Phe Ser Asp  Val Asp Leu Glu Lys  Asp Val His 
    1835                 1840                 1845             


Ser Gly  Leu Ile Gly Pro Leu  Leu Val Cys His Thr  Asn Thr Leu 
    1850                 1855                 1860             


Asn Pro  Ala His Gly Arg Gln  Val Thr Val Gln Glu  Phe Ala Leu 
    1865                 1870                 1875             


Phe Phe  Thr Ile Phe Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu 
    1880                 1885                 1890             


Asn Met  Glu Arg Asn Cys Arg  Ala Pro Cys Asn Ile  Gln Met Glu 
    1895                 1900                 1905             


Asp Pro  Thr Phe Lys Glu Asn  Tyr Arg Phe His Ala  Ile Asn Gly 
    1910                 1915                 1920             


Tyr Ile  Met Asp Thr Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln 
    1925                 1930                 1935             


Arg Ile  Arg Trp Tyr Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile 
    1940                 1945                 1950             


His Ser  Ile His Phe Ser Gly  His Val Phe Thr Val  Arg Lys Lys 
    1955                 1960                 1965             


Glu Glu  Tyr Lys Met Ala Leu  Tyr Asn Leu Tyr Pro  Gly Val Phe 
    1970                 1975                 1980             


Glu Thr  Val Glu Met Leu Pro  Ser Lys Ala Gly Ile  Trp Arg Val 
    1985                 1990                 1995             


Glu Cys  Leu Ile Gly Glu His  Leu His Ala Gly Met  Ser Thr Leu 
    2000                 2005                 2010             


Phe Leu  Val Tyr Ser Asn Lys  Cys Gln Thr Pro Leu  Gly Met Ala 
    2015                 2020                 2025             


Ser Gly  His Ile Arg Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr 
    2030                 2035                 2040             


Gly Gln  Trp Ala Pro Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser 
    2045                 2050                 2055             


Ile Asn  Ala Trp Ser Thr Lys  Glu Pro Phe Ser Trp  Ile Lys Val 
    2060                 2065                 2070             


Asp Leu  Leu Ala Pro Met Ile  Ile His Gly Ile Lys  Thr Gln Gly 
    2075                 2080                 2085             


Ala Arg  Gln Lys Phe Ser Ser  Leu Tyr Ile Ser Gln  Phe Ile Ile 
    2090                 2095                 2100             


Met Tyr  Ser Leu Asp Gly Lys  Lys Trp Gln Thr Tyr  Arg Gly Asn 
    2105                 2110                 2115             


Ser Thr  Gly Thr Leu Met Val  Phe Phe Gly Asn Val  Asp Ser Ser 
    2120                 2125                 2130             


Gly Ile  Lys His Asn Ile Phe  Asn Pro Pro Ile Ile  Ala Arg Tyr 
    2135                 2140                 2145             


Ile Arg  Leu His Pro Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg 
    2150                 2155                 2160             


Met Glu  Leu Met Gly Cys Asp  Leu Asn Ser Cys Ser  Met Pro Leu 
    2165                 2170                 2175             


Gly Met  Glu Ser Lys Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser 
    2180                 2185                 2190             


Ser Tyr  Phe Thr Asn Met Phe  Ala Thr Trp Ser Pro  Ser Lys Ala 
    2195                 2200                 2205             


Arg Leu  His Leu Gln Gly Arg  Ser Asn Ala Trp Arg  Pro Gln Val 
    2210                 2215                 2220             


Asn Asn  Pro Lys Glu Trp Leu  Gln Val Asp Phe Gln  Lys Thr Met 
    2225                 2230                 2235             


Lys Val  Thr Gly Val Thr Thr  Gln Gly Val Lys Ser  Leu Leu Thr 
    2240                 2245                 2250             


Ser Met  Tyr Val Lys Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly 
    2255                 2260                 2265             


His Gln  Trp Thr Leu Phe Phe  Gln Asn Gly Lys Val  Lys Val Phe 
    2270                 2275                 2280             


Gln Gly  Asn Gln Asp Ser Phe  Thr Pro Val Val Asn  Ser Leu Asp 
    2285                 2290                 2295             


Pro Pro  Leu Leu Thr Arg Tyr  Leu Arg Ile His Pro  Gln Ser Trp 
    2300                 2305                 2310             


Val His  Gln Ile Ala Leu Arg  Met Glu Val Leu Gly  Cys Glu Ala 
    2315                 2320                 2325             


Gln Asp  Leu Tyr 
    2330         


<210>  37
<211>  1444
<212>  PRT
<213>  artificial sequence

<220>
<223>  mature single chain Factor VIII

<400>  37

Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser Trp Asp Tyr 
1               5                   10                  15      


Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg Phe Pro Pro 
            20                  25                  30          


Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val Tyr Lys Lys 
        35                  40                  45              


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


Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln Ala Glu Val 
65                  70                  75                  80  


Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser His Pro Val 
                85                  90                  95      


Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser Glu Gly Ala 
            100                 105                 110         


Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp Asp Lys Val 
        115                 120                 125             


Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu Lys Glu Asn 
    130                 135                 140                 


Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser Tyr Leu Ser 
145                 150                 155                 160 


His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile Gly Ala Leu 
                165                 170                 175     


Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr Gln Thr Leu 
            180                 185                 190         


His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly Lys Ser Trp 
        195                 200                 205             


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


Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr Val Asn Arg 
225                 230                 235                 240 


Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val Tyr Trp His 
                245                 250                 255     


Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile Phe Leu Glu 
            260                 265                 270         


Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser Leu Glu Ile 
        275                 280                 285             


Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met Asp Leu Gly 
    290                 295                 300                 


Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His Asp Gly Met 
305                 310                 315                 320 


Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro Gln Leu Arg 
                325                 330                 335     


Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp Leu Thr Asp 
            340                 345                 350         


Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser Pro Ser Phe 
        355                 360                 365             


Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr Trp Val His 
    370                 375                 380                 


Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro Leu Val Leu 
385                 390                 395                 400 


Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn Asn Gly Pro 
                405                 410                 415     


Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met Ala Tyr Thr 
            420                 425                 430         


Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu Ser Gly Ile 
        435                 440                 445             


Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu Leu Ile Ile 
    450                 455                 460                 


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro His Gly Ile 
465                 470                 475                 480 


Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys Gly Val Lys 
                485                 490                 495     


His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe Lys Tyr Lys 
            500                 505                 510         


Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp Pro Arg Cys 
        515                 520                 525             


Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg Asp Leu Ala 
    530                 535                 540                 


Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Tyr Lys Glu Ser Val Asp 
545                 550                 555                 560 


Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val Ile Leu Phe 
                565                 570                 575     


Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu Asn Ile Gln 
            580                 585                 590         


Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp Pro Glu Phe 
        595                 600                 605             


Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val Phe Asp Ser 
    610                 615                 620                 


Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp Tyr Ile Leu 
625                 630                 635                 640 


Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe Ser Gly Tyr 
                645                 650                 655     


Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr Leu Phe Pro 
            660                 665                 670         


Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro Gly Leu Trp 
        675                 680                 685             


Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly Met Thr Ala 
    690                 695                 700                 


Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp Tyr Tyr Glu 
705                 710                 715                 720 


Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys Asn Asn Ala 
                725                 730                 735     


Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Arg Ser Thr Arg 
            740                 745                 750         


Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Thr Thr Leu Gln 
        755                 760                 765             


Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met 
    770                 775                 780                 


Lys Lys Glu Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro 
785                 790                 795                 800 


Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu 
                805                 810                 815     


Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn 
            820                 825                 830         


Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln 
        835                 840                 845             


Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu 
    850                 855                 860                 


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


Asp Asn Ile Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser 
                885                 890                 895     


Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala 
            900                 905                 910         


Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe 
        915                 920                 925             


Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys 
    930                 935                 940                 


Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His 
945                 950                 955                 960 


Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn 
                965                 970                 975     


Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe Phe 
            980                 985                 990         


Thr Ile Phe Asp Glu Thr Lys Ser  Trp Tyr Phe Thr Glu  Asn Met Glu 
        995                 1000                 1005             


Arg Asn  Cys Arg Ala Pro Cys  Asn Ile Gln Met Glu  Asp Pro Thr 
    1010                 1015                 1020             


Phe Lys  Glu Asn Tyr Arg Phe  His Ala Ile Asn Gly  Tyr Ile Met 
    1025                 1030                 1035             


Asp Thr  Leu Pro Gly Leu Val  Met Ala Gln Asp Gln  Arg Ile Arg 
    1040                 1045                 1050             


Trp Tyr  Leu Leu Ser Met Gly  Ser Asn Glu Asn Ile  His Ser Ile 
    1055                 1060                 1065             


His Phe  Ser Gly His Val Phe  Thr Val Arg Lys Lys  Glu Glu Tyr 
    1070                 1075                 1080             


Lys Met  Ala Leu Tyr Asn Leu  Tyr Pro Gly Val Phe  Glu Thr Val 
    1085                 1090                 1095             


Glu Met  Leu Pro Ser Lys Ala  Gly Ile Trp Arg Val  Glu Cys Leu 
    1100                 1105                 1110             


Ile Gly  Glu His Leu His Ala  Gly Met Ser Thr Leu  Phe Leu Val 
    1115                 1120                 1125             


Tyr Ser  Asn Lys Cys Gln Thr  Pro Leu Gly Met Ala  Ser Gly His 
    1130                 1135                 1140             


Ile Arg  Asp Phe Gln Ile Thr  Ala Ser Gly Gln Tyr  Gly Gln Trp 
    1145                 1150                 1155             


Ala Pro  Lys Leu Ala Arg Leu  His Tyr Ser Gly Ser  Ile Asn Ala 
    1160                 1165                 1170             


Trp Ser  Thr Lys Glu Pro Phe  Ser Trp Ile Lys Val  Asp Leu Leu 
    1175                 1180                 1185             


Ala Pro  Met Ile Ile His Gly  Ile Lys Thr Gln Gly  Ala Arg Gln 
    1190                 1195                 1200             


Lys Phe  Ser Ser Leu Tyr Ile  Ser Gln Phe Ile Ile  Met Tyr Ser 
    1205                 1210                 1215             


Leu Asp  Gly Lys Lys Trp Gln  Thr Tyr Arg Gly Asn  Ser Thr Gly 
    1220                 1225                 1230             


Thr Leu  Met Val Phe Phe Gly  Asn Val Asp Ser Ser  Gly Ile Lys 
    1235                 1240                 1245             


His Asn  Ile Phe Asn Pro Pro  Ile Ile Ala Arg Tyr  Ile Arg Leu 
    1250                 1255                 1260             


His Pro  Thr His Tyr Ser Ile  Arg Ser Thr Leu Arg  Met Glu Leu 
    1265                 1270                 1275             


Met Gly  Cys Asp Leu Asn Ser  Cys Ser Met Pro Leu  Gly Met Glu 
    1280                 1285                 1290             


Ser Lys  Ala Ile Ser Asp Ala  Gln Ile Thr Ala Ser  Ser Tyr Phe 
    1295                 1300                 1305             


Thr Asn  Met Phe Ala Thr Trp  Ser Pro Ser Lys Ala  Arg Leu His 
    1310                 1315                 1320             


Leu Gln  Gly Arg Ser Asn Ala  Trp Arg Pro Gln Val  Asn Asn Pro 
    1325                 1330                 1335             


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


Gly Val  Thr Thr Gln Gly Val  Lys Ser Leu Leu Thr  Ser Met Tyr 
    1355                 1360                 1365             


Val Lys  Glu Phe Leu Ile Ser  Ser Ser Gln Asp Gly  His Gln Trp 
    1370                 1375                 1380             


Thr Leu  Phe Phe Gln Asn Gly  Lys Val Lys Val Phe  Gln Gly Asn 
    1385                 1390                 1395             


Gln Asp  Ser Phe Thr Pro Val  Val Asn Ser Leu Asp  Pro Pro Leu 
    1400                 1405                 1410             


Leu Thr  Arg Tyr Leu Arg Ile  His Pro Gln Ser Trp  Val His Gln 
    1415                 1420                 1425             


Ile Ala  Leu Arg Met Glu Val  Leu Gly Cys Glu Ala  Gln Asp Leu 
    1430                 1435                 1440             


Tyr 
    


<210>  38
<211>  585
<212>  PRT
<213>  Homo sapiens

<400>  38

Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu 
1               5                   10                  15      


Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln 
            20                  25                  30          


Gln Cys Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu 
        35                  40                  45              


Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys 
    50                  55                  60                  


Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu 
65                  70                  75                  80  


Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro 
                85                  90                  95      


Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu 
            100                 105                 110         


Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His 
        115                 120                 125             


Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg 
    130                 135                 140                 


Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg 
145                 150                 155                 160 


Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala 
                165                 170                 175     


Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Asp Glu Gly Lys Ala Ser 
            180                 185                 190         


Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser Leu Gln Lys Phe Gly Glu 
        195                 200                 205             


Arg Ala Phe Lys Ala Trp Ala Val Ala Arg Leu Ser Gln Arg Phe Pro 
    210                 215                 220                 


Lys Ala Glu Phe Ala Glu Val Ser Lys Leu Val Thr Asp Leu Thr Lys 
225                 230                 235                 240 


Val His Thr Glu Cys Cys His Gly Asp Leu Leu Glu Cys Ala Asp Asp 
                245                 250                 255     


Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu Asn Gln Asp Ser Ile Ser 
            260                 265                 270         


Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro Leu Leu Glu Lys Ser His 
        275                 280                 285             


Cys Ile Ala Glu Val Glu Asn Asp Glu Met Pro Ala Asp Leu Pro Ser 
    290                 295                 300                 


Leu Ala Ala Asp Phe Val Glu Ser Lys Asp Val Cys Lys Asn Tyr Ala 
305                 310                 315                 320 


Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu Tyr Ala Arg 
                325                 330                 335     


Arg His Pro Asp Tyr Ser Val Val Leu Leu Leu Arg Leu Ala Lys Thr 
            340                 345                 350         


Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala Ala Ala Asp Pro His Glu 
        355                 360                 365             


Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys Pro Leu Val Glu Glu Pro 
    370                 375                 380                 


Gln Asn Leu Ile Lys Gln Asn Cys Glu Leu Phe Glu Gln Leu Gly Glu 
385                 390                 395                 400 


Tyr Lys Phe Gln Asn Ala Leu Leu Val Arg Tyr Thr Lys Lys Val Pro 
                405                 410                 415     


Gln Val Ser Thr Pro Thr Leu Val Glu Val Ser Arg Asn Leu Gly Lys 
            420                 425                 430         


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


Ala Glu Asp Tyr Leu Ser Val Val Leu Asn Gln Leu Cys Val Leu His 
    450                 455                 460                 


Glu Lys Thr Pro Val Ser Asp Arg Val Thr Lys Cys Cys Thr Glu Ser 
465                 470                 475                 480 


Leu Val Asn Arg Arg Pro Cys Phe Ser Ala Leu Glu Val Asp Glu Thr 
                485                 490                 495     


Tyr Val Pro Lys Glu Phe Asn Ala Glu Thr Phe Thr Phe His Ala Asp 
            500                 505                 510         


Ile Cys Thr Leu Ser Glu Lys Glu Arg Gln Ile Lys Lys Gln Thr Ala 
        515                 520                 525             


Leu Val Glu Leu Val Lys His Lys Pro Lys Ala Thr Lys Glu Gln Leu 
    530                 535                 540                 


Lys Ala Val Met Asp Asp Phe Ala Ala Phe Val Glu Lys Cys Cys Lys 
545                 550                 555                 560 


Ala Asp Asp Lys Glu Thr Cys Phe Ala Glu Glu Gly Lys Lys Leu Val 
                565                 570                 575     


Ala Ala Ser Gln Ala Ala Leu Gly Leu 
            580                 585 


