                         SEQUENCE LISTING

<110>  AAVnergen
       WANG , Qizhao
       YU, Daozhan
 
<120>  MODIFIED PLASMA CLOTTING FACTOR VIII AND USE THEREOF

<130>  2037-001 US (141088)

<160>  18    

<170>  PatentIn version 3.5

<210>  1
<211>  7056
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  Human Factor VIII

<400>  1
atgcaaatag agctctccac ctgcttcttt ctgtgccttt tgcgattctg ctttagtgcc       60

accagaagat actacctggg tgcagtggaa ctgtcatggg actatatgca aagtgatctc      120

ggtgagctgc ctgtggacgc aagatttcct cctagagtgc caaaatcttt tccattcaac      180

acctcagtcg tgtacaaaaa gactctgttt gtagaattca cggatcacct tttcaacatc      240

gctaagccaa ggccaccctg gatgggtctg ctaggtccta ccatccaggc tgaggtttat      300

gatacagtgg tcattacact taagaacatg gcttcccatc ctgtcagtct tcatgctgtt      360

ggtgtatcct actggaaagc ttctgaggga gctgaatatg atgatcagac cagtcaaagg      420

gagaaagaag atgataaagt cttccctggt ggaagccata catatgtctg gcaggtcctg      480

aaagagaatg gtccaatggc ctctgaccca ctgtgcctta cctactcata tctttctcat      540

gtggacctgg taaaagactt gaattcaggc ctcattggag ccctactagt atgtagagaa      600

gggagtctgg ccaaggaaaa gacacagacc ttgcacaaat ttatactact ttttgctgta      660

tttgatgaag ggaaaagttg gcactcagaa acaaagaact ccttgatgca ggatagggat      720

gctgcatctg ctcgggcctg gcctaaaatg cacacagtca atggttatgt aaacaggtct      780

ctgccaggtc tgattggatg ccacaggaaa tcagtctatt ggcatgtgat tggaatgggc      840

accactcctg aagtgcactc aatattcctc gaaggtcaca catttcttgt gaggaaccat      900

cgccaggcgt ccttggaaat ctcgccaata actttcctta ctgctcaaac actcttgatg      960

gaccttggac agtttctact gttttgtcat atctcttccc accaacatga tggcatggaa     1020

gcttatgtca aagtagacag ctgtccagag gaaccccaac tacgaatgaa aaataatgaa     1080

gaagcggaag actatgatga tgatcttact gattctgaaa tggatgtggt caggtttgat     1140

gatgacaact ctccttcctt tatccaaatt cgctcagttg ccaagaagca tcctaaaact     1200

tgggtacatt acattgctgc tgaagaggag gactgggact atgctccctt agtcctcgcc     1260

cccgatgaca gaagttataa aagtcaatat ttgaacaatg gccctcagcg gattggtagg     1320

aagtacaaaa aagtccgatt tatggcatac acagatgaaa cctttaagac tcgtgaagct     1380

attcagcatg aatcaggaat cttgggacct ttactttatg gggaagttgg agacacactg     1440

ttgattatat ttaagaatca agcaagcaga ccatataaca tctaccctca cggaatcact     1500

gatgtccgtc ctttgtattc aaggagatta ccaaaaggtg taaaacattt gaaggatttt     1560

ccaattctgc caggagaaat attcaaatat aaatggacag tgactgtaga agatgggcca     1620

actaaatcag atcctcggtg cctgacccgc tattactcta gtttcgttaa tatggagaga     1680

gatctagctt caggactcat tggccctctc ctcatctgct acaaagaatc tgtagatcaa     1740

agaggaaacc agataatgtc agacaagagg aatgtcatcc tgttttctgt atttgatgag     1800

aaccgaagct ggtacctcac agagaatata caacgctttc tccccaatcc agctggagtg     1860

cagcttgagg atccagagtt ccaagcctcc aacatcatgc acagcatcaa tggctatgtt     1920

tttgatagtt tgcagttgtc agtttgtttg catgaggtgg catactggta cattctaagc     1980

attggagcac agactgactt cctttctgtc ttcttctctg gatatacctt caaacacaaa     2040

atggtctatg aagacacact caccctattc ccattctcag gagaaactgt cttcatgtcg     2100

atggaaaacc caggtctatg gattctgggg tgccacaact cagactttcg gaacagaggc     2160

atgaccgcct tactgaaggt ttctagttgt gacaagaaca ctggtgatta ttacgaggac     2220

agttatgaag atatttcagc atacttgctg agtaaaaaca atgccattga accaagaagc     2280

ttctcccaga attcaagaca ccctagcact aggcaaaagc aatttaatgc caccacaatt     2340

ccagaaaatg acatagagaa gactgaccct tggtttgcac acagaacacc tatgcctaaa     2400

atacaaaatg tctcctctag tgatttgttg atgctcttgc gacagagtcc tactccacat     2460

gggctatcct tatctgatct ccaagaagcc aaatatgaga ctttttctga tgatccatca     2520

cctggagcaa tagacagtaa taacagcctg tctgaaatga cacacttcag gccacagctc     2580

catcacagtg gggacatggt atttacccct gagtcaggcc tccaattaag attaaatgag     2640

aaactgggga caactgcagc aacagagttg aagaaacttg atttcaaagt ttctagtaca     2700

tcaaataatc tgatttcaac aattccatca gacaatttgg cagcaggtac tgataataca     2760

agttccttag gacccccaag tatgccagtt cattatgata gtcaattaga taccactcta     2820

tttggcaaaa agtcatctcc ccttactgag tctggtggac ctctgagctt gagtgaagaa     2880

aataatgatt caaagttgtt agaatcaggt ttaatgaata gccaagaaag ttcatgggga     2940

aaaaatgtat cgtcaacaga gagtggtagg ttatttaaag ggaaaagagc tcatggacct     3000

gctttgttga ctaaagataa tgccttattc aaagttagca tctctttgtt aaagacaaac     3060

aaaacttcca ataattcagc aactaataga aagactcaca ttgatggccc atcattatta     3120

attgagaata gtccatcagt ctggcaaaat atattagaaa gtgacactga gtttaaaaaa     3180

gtgacacctt tgattcatga cagaatgctt atggacaaaa atgctacagc tttgaggcta     3240

aatcatatgt caaataaaac tacttcatca aaaaacatgg aaatggtcca acagaaaaaa     3300

gagggcccca ttccaccaga tgcacaaaat ccagatatgt cgttctttaa gatgctattc     3360

ttgccagaat cagcaaggtg gatacaaagg actcatggaa agaactctct gaactctggg     3420

caaggcccca gtccaaagca attagtatcc ttaggaccag aaaaatctgt ggaaggtcag     3480

aatttcttgt ctgagaaaaa caaagtggta gtaggaaagg gtgaatttac aaaggacgta     3540

ggactcaaag agatggtttt tccaagcagc agaaacctat ttcttactaa cttggataat     3600

ttacatgaaa ataatacaca caatcaagaa aaaaaaattc aggaagaaat agaaaagaag     3660

gaaacattaa tccaagagaa tgtagttttg cctcagatac atacagtgac tggcactaag     3720

aatttcatga agaacctttt cttactgagc actaggcaaa atgtagaagg ttcatatgac     3780

ggggcatatg ctccagtact tcaagatttt aggtcattaa atgattcaac aaatagaaca     3840

aagaaacaca cagctcattt ctcaaaaaaa ggggaggaag aaaacttgga aggcttggga     3900

aatcaaacca agcaaattgt agagaaatat gcatgcacca caaggatatc tcctaataca     3960

agccagcaga attttgtcac gcaacgtagt aagagagctt tgaaacaatt cagactccca     4020

ctagaagaaa cagaacttga aaaaaggata attgtggatg acacctcaac ccagtggtcc     4080

aaaaacatga aacatttgac cccgagcacc ctcacacaga tagactacaa tgagaaggag     4140

aaaggggcca ttactcagtc tcccttatca gattgcctta cgaggagtca tagcatccct     4200

caagcaaata gatctccatt acccattgca aaggtatcat catttccatc tattagacct     4260

atatatctga ccagggtcct attccaagac aactcttctc atcttccagc agcatcttat     4320

agaaagaaag attctggggt ccaagaaagc agtcatttct tacaaggagc caaaaaaaat     4380

aacctttctt tagccattct aaccttggag atgactggtg atcaaagaga ggttggctcc     4440

ctggggacaa gtgccacaaa ttcagtcaca tacaagaaag ttgagaacac tgttctcccg     4500

aaaccagact tgcccaaaac atctggcaaa gttgaattgc ttccaaaagt tcacatttat     4560

cagaaggacc tattccctac ggaaactagc aatgggtctc ctggccatct ggatctcgtg     4620

gaagggagcc ttcttcaggg aacagaggga gcgattaagt ggaatgaagc aaacagacct     4680

ggaaaagttc cctttctgag agtagcaaca gaaagctctg caaagactcc ctccaagcta     4740

ttggatcctc ttgcttggga taaccactat ggtactcaga taccaaaaga agagtggaaa     4800

tcccaagaga agtcaccaga aaaaacagct tttaagaaaa aggataccat tttgtccctg     4860

aacgcttgtg aaagcaatca tgcaatagca gcaataaatg agggacaaaa taagcccgaa     4920

atagaagtca cctgggcaaa gcaaggtagg actgaaaggc tgtgctctca aaacccacca     4980

gtcttgaaac gccatcaacg ggaaataact cgtactactc ttcagtcaga tcaagaggaa     5040

attgactatg atgataccat atcagttgaa atgaagaagg aagattttga catttatgat     5100

gaggatgaaa atcagagccc ccgcagcttt caaaagaaaa cacgacacta ttttattgct     5160

gcagtggaga ggctctggga ttatgggatg agtagctccc cacatgttct aagaaacagg     5220

gctcagagtg gcagtgtccc tcagttcaag aaagttgttt tccaggaatt tactgatggc     5280

tcctttactc agcccttata ccgtggagaa ctaaatgaac atttgggact cctggggcca     5340

tatataagag cagaagttga agataatatc atggtaactt tcagaaatca ggcctctcgt     5400

ccctattcct tctattctag ccttatttct tatgaggaag atcagaggca aggagcagaa     5460

cctagaaaaa actttgtcaa gcctaatgaa accaaaactt acttttggaa agtgcaacat     5520

catatggcac ccactaaaga tgagtttgac tgcaaagcct gggcttattt ctctgatgtt     5580

gacctggaaa aagatgtgca ctcaggcctg attggacccc ttctggtctg ccacactaac     5640

acactgaacc ctgctcatgg gagacaagtg acagtacagg aatttgctct gtttttcacc     5700

atctttgatg agaccaaaag ctggtacttc actgaaaata tggaaagaaa ctgcagggct     5760

ccctgcaata tccagatgga agatcccact tttaaagaga attatcgctt ccatgcaatc     5820

aatggctaca taatggatac actacctggc ttagtaatgg ctcaggatca aaggattcga     5880

tggtatctgc tcagcatggg cagcaatgaa aacatccatt ctattcattt cagtggacat     5940

gtgttcactg tacgaaaaaa agaggagtat aaaatggcac tgtacaatct ctatccaggt     6000

gtttttgaga cagtggaaat gttaccatcc aaagctggaa tttggcgggt ggaatgcctt     6060

attggcgagc atctacatgc tgggatgagc acactttttc tggtgtacag caataagtgt     6120

cagactcccc tgggaatggc ttctggacac attagagatt ttcagattac agcttcagga     6180

caatatggac agtgggcccc aaagctggcc agacttcatt attccggatc aatcaatgcc     6240

tggagcacca aggagccctt ttcttggatc aaggtggatc tgttggcacc aatgattatt     6300

cacggcatca agacccaggg tgcccgtcag aagttctcca gcctctacat ctctcagttt     6360

atcatcatgt atagtcttga tgggaagaag tggcagactt atcgaggaaa ttccactgga     6420

accttaatgg tcttctttgg caatgtggat tcatctggga taaaacacaa tatttttaac     6480

cctccaatta ttgctcgata catccgtttg cacccaactc attatagcat tcgcagcact     6540

cttcgcatgg agttgatggg ctgtgattta aatagttgca gcatgccatt gggaatggag     6600

agtaaagcaa tatcagatgc acagattact gcttcatcct actttaccaa tatgtttgcc     6660

acctggtctc cttcaaaagc tcgacttcac ctccaaggga ggagtaatgc ctggagacct     6720

caggtgaata atccaaaaga gtggctgcaa gtggacttcc agaagacaat gaaagtcaca     6780

ggagtaacta ctcagggagt aaaatctctg cttaccagca tgtatgtgaa ggagttcctc     6840

atctccagca gtcaagatgg ccatcagtgg actctctttt ttcagaatgg caaagtaaag     6900

gtttttcagg gaaatcaaga ctccttcaca cctgtggtga actctctaga cccaccgtta     6960

ctgactcgct accttcgaat tcacccccag agttgggtgc accagattgc cctgaggatg     7020

gaggttctgg gctgcgaggc acaggacctc tactga                               7056


<210>  2
<211>  19
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  Human factor VIII signal peptide

<400>  2

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser 
            


<210>  3
<211>  2351
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  Human Factor VIII with signal peptide

<400>  3

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Ser Arg His Pro 
        755                 760                 765             


Ser Thr Arg Gln Lys Gln Phe Asn Ala Thr Thr Ile Pro Glu Asn Asp 
    770                 775                 780                 


Ile Glu Lys Thr Asp Pro Trp Phe Ala His Arg Thr Pro Met Pro Lys 
785                 790                 795                 800 


Ile Gln Asn Val Ser Ser Ser Asp Leu Leu Met Leu Leu Arg Gln Ser 
                805                 810                 815     


Pro Thr Pro His Gly Leu Ser Leu Ser Asp Leu Gln Glu Ala Lys Tyr 
            820                 825                 830         


Glu Thr Phe Ser Asp Asp Pro Ser Pro Gly Ala Ile Asp Ser Asn Asn 
        835                 840                 845             


Ser Leu Ser Glu Met Thr His Phe Arg Pro Gln Leu His His Ser Gly 
    850                 855                 860                 


Asp Met Val Phe Thr Pro Glu Ser Gly Leu Gln Leu Arg Leu Asn Glu 
865                 870                 875                 880 


Lys Leu Gly Thr Thr Ala Ala Thr Glu Leu Lys Lys Leu Asp Phe Lys 
                885                 890                 895     


Val Ser Ser Thr Ser Asn Asn Leu Ile Ser Thr Ile Pro Ser Asp Asn 
            900                 905                 910         


Leu Ala Ala Gly Thr Asp Asn Thr Ser Ser Leu Gly Pro Pro Ser Met 
        915                 920                 925             


Pro Val His Tyr Asp Ser Gln Leu Asp Thr Thr Leu Phe Gly Lys Lys 
    930                 935                 940                 


Ser Ser Pro Leu Thr Glu Ser Gly Gly Pro Leu Ser Leu Ser Glu Glu 
945                 950                 955                 960 


Asn Asn Asp Ser Lys Leu Leu Glu Ser Gly Leu Met Asn Ser Gln Glu 
                965                 970                 975     


Ser Ser Trp Gly Lys Asn Val Ser Ser Thr Glu Ser Gly Arg Leu Phe 
            980                 985                 990         


Lys Gly Lys Arg Ala His Gly Pro  Ala Leu Leu Thr Lys  Asp Asn Ala 
        995                 1000                 1005             


Leu Phe  Lys Val Ser Ile Ser  Leu Leu Lys Thr Asn  Lys Thr Ser 
    1010                 1015                 1020             


Asn Asn  Ser Ala Thr Asn Arg  Lys Thr His Ile Asp  Gly Pro Ser 
    1025                 1030                 1035             


Leu Leu  Ile Glu Asn Ser Pro  Ser Val Trp Gln Asn  Ile Leu Glu 
    1040                 1045                 1050             


Ser Asp  Thr Glu Phe Lys Lys  Val Thr Pro Leu Ile  His Asp Arg 
    1055                 1060                 1065             


Met Leu  Met Asp Lys Asn Ala  Thr Ala Leu Arg Leu  Asn His Met 
    1070                 1075                 1080             


Ser Asn  Lys Thr Thr Ser Ser  Lys Asn Met Glu Met  Val Gln Gln 
    1085                 1090                 1095             


Lys Lys  Glu Gly Pro Ile Pro  Pro Asp Ala Gln Asn  Pro Asp Met 
    1100                 1105                 1110             


Ser Phe  Phe Lys Met Leu Phe  Leu Pro Glu Ser Ala  Arg Trp Ile 
    1115                 1120                 1125             


Gln Arg  Thr His Gly Lys Asn  Ser Leu Asn Ser Gly  Gln Gly Pro 
    1130                 1135                 1140             


Ser Pro  Lys Gln Leu Val Ser  Leu Gly Pro Glu Lys  Ser Val Glu 
    1145                 1150                 1155             


Gly Gln  Asn Phe Leu Ser Glu  Lys Asn Lys Val Val  Val Gly Lys 
    1160                 1165                 1170             


Gly Glu  Phe Thr Lys Asp Val  Gly Leu Lys Glu Met  Val Phe Pro 
    1175                 1180                 1185             


Ser Ser  Arg Asn Leu Phe Leu  Thr Asn Leu Asp Asn  Leu His Glu 
    1190                 1195                 1200             


Asn Asn  Thr His Asn Gln Glu  Lys Lys Ile Gln Glu  Glu Ile Glu 
    1205                 1210                 1215             


Lys Lys  Glu Thr Leu Ile Gln  Glu Asn Val Val Leu  Pro Gln Ile 
    1220                 1225                 1230             


His Thr  Val Thr Gly Thr Lys  Asn Phe Met Lys Asn  Leu Phe Leu 
    1235                 1240                 1245             


Leu Ser  Thr Arg Gln Asn Val  Glu Gly Ser Tyr Asp  Gly Ala Tyr 
    1250                 1255                 1260             


Ala Pro  Val Leu Gln Asp Phe  Arg Ser Leu Asn Asp  Ser Thr Asn 
    1265                 1270                 1275             


Arg Thr  Lys Lys His Thr Ala  His Phe Ser Lys Lys  Gly Glu Glu 
    1280                 1285                 1290             


Glu Asn  Leu Glu Gly Leu Gly  Asn Gln Thr Lys Gln  Ile Val Glu 
    1295                 1300                 1305             


Lys Tyr  Ala Cys Thr Thr Arg  Ile Ser Pro Asn Thr  Ser Gln Gln 
    1310                 1315                 1320             


Asn Phe  Val Thr Gln Arg Ser  Lys Arg Ala Leu Lys  Gln Phe Arg 
    1325                 1330                 1335             


Leu Pro  Leu Glu Glu Thr Glu  Leu Glu Lys Arg Ile  Ile Val Asp 
    1340                 1345                 1350             


Asp Thr  Ser Thr Gln Trp Ser  Lys Asn Met Lys His  Leu Thr Pro 
    1355                 1360                 1365             


Ser Thr  Leu Thr Gln Ile Asp  Tyr Asn Glu Lys Glu  Lys Gly Ala 
    1370                 1375                 1380             


Ile Thr  Gln Ser Pro Leu Ser  Asp Cys Leu Thr Arg  Ser His Ser 
    1385                 1390                 1395             


Ile Pro  Gln Ala Asn Arg Ser  Pro Leu Pro Ile Ala  Lys Val Ser 
    1400                 1405                 1410             


Ser Phe  Pro Ser Ile Arg Pro  Ile Tyr Leu Thr Arg  Val Leu Phe 
    1415                 1420                 1425             


Gln Asp  Asn Ser Ser His Leu  Pro Ala Ala Ser Tyr  Arg Lys Lys 
    1430                 1435                 1440             


Asp Ser  Gly Val Gln Glu Ser  Ser His Phe Leu Gln  Gly Ala Lys 
    1445                 1450                 1455             


Lys Asn  Asn Leu Ser Leu Ala  Ile Leu Thr Leu Glu  Met Thr Gly 
    1460                 1465                 1470             


Asp Gln  Arg Glu Val Gly Ser  Leu Gly Thr Ser Ala  Thr Asn Ser 
    1475                 1480                 1485             


Val Thr  Tyr Lys Lys Val Glu  Asn Thr Val Leu Pro  Lys Pro Asp 
    1490                 1495                 1500             


Leu Pro  Lys Thr Ser Gly Lys  Val Glu Leu Leu Pro  Lys Val His 
    1505                 1510                 1515             


Ile Tyr  Gln Lys Asp Leu Phe  Pro Thr Glu Thr Ser  Asn Gly Ser 
    1520                 1525                 1530             


Pro Gly  His Leu Asp Leu Val  Glu Gly Ser Leu Leu  Gln Gly Thr 
    1535                 1540                 1545             


Glu Gly  Ala Ile Lys Trp Asn  Glu Ala Asn Arg Pro  Gly Lys Val 
    1550                 1555                 1560             


Pro Phe  Leu Arg Val Ala Thr  Glu Ser Ser Ala Lys  Thr Pro Ser 
    1565                 1570                 1575             


Lys Leu  Leu Asp Pro Leu Ala  Trp Asp Asn His Tyr  Gly Thr Gln 
    1580                 1585                 1590             


Ile Pro  Lys Glu Glu Trp Lys  Ser Gln Glu Lys Ser  Pro Glu Lys 
    1595                 1600                 1605             


Thr Ala  Phe Lys Lys Lys Asp  Thr Ile Leu Ser Leu  Asn Ala Cys 
    1610                 1615                 1620             


Glu Ser  Asn His Ala Ile Ala  Ala Ile Asn Glu Gly  Gln Asn Lys 
    1625                 1630                 1635             


Pro Glu  Ile Glu Val Thr Trp  Ala Lys Gln Gly Arg  Thr Glu Arg 
    1640                 1645                 1650             


Leu Cys  Ser Gln Asn Pro Pro  Val Leu Lys Arg His  Gln Arg Glu 
    1655                 1660                 1665             


Ile Thr  Arg Thr Thr Leu Gln  Ser Asp Gln Glu Glu  Ile Asp Tyr 
    1670                 1675                 1680             


Asp Asp  Thr Ile Ser Val Glu  Met Lys Lys Glu Asp  Phe Asp Ile 
    1685                 1690                 1695             


Tyr Asp  Glu Asp Glu Asn Gln  Ser Pro Arg Ser Phe  Gln Lys Lys 
    1700                 1705                 1710             


Thr Arg  His Tyr Phe Ile Ala  Ala Val Glu Arg Leu  Trp Asp Tyr 
    1715                 1720                 1725             


Gly Met  Ser Ser Ser Pro His  Val Leu Arg Asn Arg  Ala Gln Ser 
    1730                 1735                 1740             


Gly Ser  Val Pro Gln Phe Lys  Lys Val Val Phe Gln  Glu Phe Thr 
    1745                 1750                 1755             


Asp Gly  Ser Phe Thr Gln Pro  Leu Tyr Arg Gly Glu  Leu Asn Glu 
    1760                 1765                 1770             


His Leu  Gly Leu Leu Gly Pro  Tyr Ile Arg Ala Glu  Val Glu Asp 
    1775                 1780                 1785             


Asn Ile  Met Val Thr Phe Arg  Asn Gln Ala Ser Arg  Pro Tyr Ser 
    1790                 1795                 1800             


Phe Tyr  Ser Ser Leu Ile Ser  Tyr Glu Glu Asp Gln  Arg Gln Gly 
    1805                 1810                 1815             


Ala Glu  Pro Arg Lys Asn Phe  Val Lys Pro Asn Glu  Thr Lys Thr 
    1820                 1825                 1830             


Tyr Phe  Trp Lys Val Gln His  His Met Ala Pro Thr  Lys Asp Glu 
    1835                 1840                 1845             


Phe Asp  Cys Lys Ala Trp Ala  Tyr Phe Ser Asp Val  Asp Leu Glu 
    1850                 1855                 1860             


Lys Asp  Val His Ser Gly Leu  Ile Gly Pro Leu Leu  Val Cys His 
    1865                 1870                 1875             


Thr Asn  Thr Leu Asn Pro Ala  His Gly Arg Gln Val  Thr Val Gln 
    1880                 1885                 1890             


Glu Phe  Ala Leu Phe Phe Thr  Ile Phe Asp Glu Thr  Lys Ser Trp 
    1895                 1900                 1905             


Tyr Phe  Thr Glu Asn Met Glu  Arg Asn Cys Arg Ala  Pro Cys Asn 
    1910                 1915                 1920             


Ile Gln  Met Glu Asp Pro Thr  Phe Lys Glu Asn Tyr  Arg Phe His 
    1925                 1930                 1935             


Ala Ile  Asn Gly Tyr Ile Met  Asp Thr Leu Pro Gly  Leu Val Met 
    1940                 1945                 1950             


Ala Gln  Asp Gln Arg Ile Arg  Trp Tyr Leu Leu Ser  Met Gly Ser 
    1955                 1960                 1965             


Asn Glu  Asn Ile His Ser Ile  His Phe Ser Gly His  Val Phe Thr 
    1970                 1975                 1980             


Val Arg  Lys Lys Glu Glu Tyr  Lys Met Ala Leu Tyr  Asn Leu Tyr 
    1985                 1990                 1995             


Pro Gly  Val Phe Glu Thr Val  Glu Met Leu Pro Ser  Lys Ala Gly 
    2000                 2005                 2010             


Ile Trp  Arg Val Glu Cys Leu  Ile Gly Glu His Leu  His Ala Gly 
    2015                 2020                 2025             


Met Ser  Thr Leu Phe Leu Val  Tyr Ser Asn Lys Cys  Gln Thr Pro 
    2030                 2035                 2040             


Leu Gly  Met Ala Ser Gly His  Ile Arg Asp Phe Gln  Ile Thr Ala 
    2045                 2050                 2055             


Ser Gly  Gln Tyr Gly Gln Trp  Ala Pro Lys Leu Ala  Arg Leu His 
    2060                 2065                 2070             


Tyr Ser  Gly Ser Ile Asn Ala  Trp Ser Thr Lys Glu  Pro Phe Ser 
    2075                 2080                 2085             


Trp Ile  Lys Val Asp Leu Leu  Ala Pro Met Ile Ile  His Gly Ile 
    2090                 2095                 2100             


Lys Thr  Gln Gly Ala Arg Gln  Lys Phe Ser Ser Leu  Tyr Ile Ser 
    2105                 2110                 2115             


Gln Phe  Ile Ile Met Tyr Ser  Leu Asp Gly Lys Lys  Trp Gln Thr 
    2120                 2125                 2130             


Tyr Arg  Gly Asn Ser Thr Gly  Thr Leu Met Val Phe  Phe Gly Asn 
    2135                 2140                 2145             


Val Asp  Ser Ser Gly Ile Lys  His Asn Ile Phe Asn  Pro Pro Ile 
    2150                 2155                 2160             


Ile Ala  Arg Tyr Ile Arg Leu  His Pro Thr His Tyr  Ser Ile Arg 
    2165                 2170                 2175             


Ser Thr  Leu Arg Met Glu Leu  Met Gly Cys Asp Leu  Asn Ser Cys 
    2180                 2185                 2190             


Ser Met  Pro Leu Gly Met Glu  Ser Lys Ala Ile Ser  Asp Ala Gln 
    2195                 2200                 2205             


Ile Thr  Ala Ser Ser Tyr Phe  Thr Asn Met Phe Ala  Thr Trp Ser 
    2210                 2215                 2220             


Pro Ser  Lys Ala Arg Leu His  Leu Gln Gly Arg Ser  Asn Ala Trp 
    2225                 2230                 2235             


Arg Pro  Gln Val Asn Asn Pro  Lys Glu Trp Leu Gln  Val Asp Phe 
    2240                 2245                 2250             


Gln Lys  Thr Met Lys Val Thr  Gly Val Thr Thr Gln  Gly Val Lys 
    2255                 2260                 2265             


Ser Leu  Leu Thr Ser Met Tyr  Val Lys Glu Phe Leu  Ile Ser Ser 
    2270                 2275                 2280             


Ser Gln  Asp Gly His Gln Trp  Thr Leu Phe Phe Gln  Asn Gly Lys 
    2285                 2290                 2295             


Val Lys  Val Phe Gln Gly Asn  Gln Asp Ser Phe Thr  Pro Val Val 
    2300                 2305                 2310             


Asn Ser  Leu Asp Pro Pro Leu  Leu Thr Arg Tyr Leu  Arg Ile His 
    2315                 2320                 2325             


Pro Gln  Ser Trp Val His Gln  Ile Ala Leu Arg Met  Glu Val Leu 
    2330                 2335                 2340             


Gly Cys  Glu Ala Gln Asp Leu  Tyr 
    2345                 2350     


<210>  4
<211>  2332
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  Human Factor VIII without signal peptide

<400>  4

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 Pro 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>  5
<211>  1457
<212>  PRT
<213>  artificial

<220>
<223>  artificial sequence


<220>
<221>  misc_feature
<223>  B-domainless human Factor VIII (hBDDF8) with signal peptide

<400>  5

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu 
        755                 760                 765             


Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
    770                 775                 780                 


Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu 
785                 790                 795                 800 


Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser Pro Arg Ser Phe 
                805                 810                 815     


Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp 
            820                 825                 830         


Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln 
        835                 840                 845             


Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr 
    850                 855                 860                 


Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His 
865                 870                 875                 880 


Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile 
                885                 890                 895     


Met Val Thr Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
            900                 905                 910         


Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg 
        915                 920                 925             


Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val 
    930                 935                 940                 


Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp 
945                 950                 955                 960 


Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu 
                965                 970                 975     


Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His 
            980                 985                 990         


Gly Arg Gln Val Thr Val Gln Glu  Phe Ala Leu Phe Phe  Thr Ile Phe 
        995                 1000                 1005             


Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu Asn Met  Glu Arg Asn 
    1010                 1015                 1020             


Cys Arg  Ala Pro Cys Asn Ile  Gln Met Glu Asp Pro  Thr Phe Lys 
    1025                 1030                 1035             


Glu Asn  Tyr Arg Phe His Ala  Ile Asn Gly Tyr Ile  Met Asp Thr 
    1040                 1045                 1050             


Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln Arg Ile  Arg Trp Tyr 
    1055                 1060                 1065             


Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile His Ser  Ile His Phe 
    1070                 1075                 1080             


Ser Gly  His Val Phe Thr Val  Arg Lys Lys Glu Glu  Tyr Lys Met 
    1085                 1090                 1095             


Ala Leu  Tyr Asn Leu Tyr Pro  Gly Val Phe Glu Thr  Val Glu Met 
    1100                 1105                 1110             


Leu Pro  Ser Lys Ala Gly Ile  Trp Arg Val Glu Cys  Leu Ile Gly 
    1115                 1120                 1125             


Glu His  Leu His Ala Gly Met  Ser Thr Leu Phe Leu  Val Tyr Ser 
    1130                 1135                 1140             


Asn Lys  Cys Gln Thr Pro Leu  Gly Met Ala Ser Gly  His Ile Arg 
    1145                 1150                 1155             


Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr Gly Gln  Trp Ala Pro 
    1160                 1165                 1170             


Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser Ile Asn  Ala Trp Ser 
    1175                 1180                 1185             


Thr Lys  Glu Pro Phe Ser Trp  Ile Lys Val Asp Leu  Leu Ala Pro 
    1190                 1195                 1200             


Met Ile  Ile His Gly Ile Lys  Thr Gln Gly Ala Arg  Gln Lys Phe 
    1205                 1210                 1215             


Ser Ser  Leu Tyr Ile Ser Gln  Phe Ile Ile Met Tyr  Ser Leu Asp 
    1220                 1225                 1230             


Gly Lys  Lys Trp Gln Thr Tyr  Arg Gly Asn Ser Thr  Gly Thr Leu 
    1235                 1240                 1245             


Met Val  Phe Phe Gly Asn Val  Asp Ser Ser Gly Ile  Lys His Asn 
    1250                 1255                 1260             


Ile Phe  Asn Pro Pro Ile Ile  Ala Arg Tyr Ile Arg  Leu His Pro 
    1265                 1270                 1275             


Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg Met Glu  Leu Met Gly 
    1280                 1285                 1290             


Cys Asp  Leu Asn Ser Cys Ser  Met Pro Leu Gly Met  Glu Ser Lys 
    1295                 1300                 1305             


Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser Ser Tyr  Phe Thr Asn 
    1310                 1315                 1320             


Met Phe  Ala Thr Trp Ser Pro  Ser Lys Ala Arg Leu  His Leu Gln 
    1325                 1330                 1335             


Gly Arg  Ser Asn Ala Trp Arg  Pro Gln Val Asn Asn  Pro Lys Glu 
    1340                 1345                 1350             


Trp Leu  Gln Val Asp Phe Gln  Lys Thr Met Lys Val  Thr Gly Val 
    1355                 1360                 1365             


Thr Thr  Gln Gly Val Lys Ser  Leu Leu Thr Ser Met  Tyr Val Lys 
    1370                 1375                 1380             


Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly His Gln  Trp Thr Leu 
    1385                 1390                 1395             


Phe Phe  Gln Asn Gly Lys Val  Lys Val Phe Gln Gly  Asn Gln Asp 
    1400                 1405                 1410             


Ser Phe  Thr Pro Val Val Asn  Ser Leu Asp Pro Pro  Leu Leu Thr 
    1415                 1420                 1425             


Arg Tyr  Leu Arg Ile His Pro  Gln Ser Trp Val His  Gln Ile Ala 
    1430                 1435                 1440             


Leu Arg  Met Glu Val Leu Gly  Cys Glu Ala Gln Asp  Leu Tyr 
    1445                 1450                 1455         


<210>  6
<211>  1438
<212>  PRT
<213>  artificial

<220>
<223>  artificial sequence


<220>
<221>  misc_feature
<223>  B-domainless human Factor VIII (hBDDF8) without native signal 
       peptide

<400>  6

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 Pro Pro Val Leu Lys Arg His 
            740                 745                 750         


Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln Glu Glu Ile 
        755                 760                 765             


Asp Tyr Asp Asp Thr Ile Ser Val Glu Met Lys Lys Glu Asp Phe Asp 
    770                 775                 780                 


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


Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly 
                805                 810                 815     


Met Ser Ser Ser Pro His Val Leu Arg Asn Arg Ala Gln Ser Gly Ser 
            820                 825                 830         


Val Pro Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser 
        835                 840                 845             


Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu 
    850                 855                 860                 


Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile Met Val Thr 
865                 870                 875                 880 


Phe Arg Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile 
                885                 890                 895     


Ser Tyr Glu Glu Asp Gln Arg Gln Gly Ala Glu Pro Arg Lys Asn Phe 
            900                 905                 910         


Val Lys Pro Asn Glu Thr Lys Thr Tyr Phe Trp Lys Val Gln His His 
        915                 920                 925             


Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe 
    930                 935                 940                 


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


Leu Leu Val Cys His Thr Asn Thr Leu Asn Pro Ala His Gly Arg Gln 
                965                 970                 975     


Val Thr Val Gln Glu Phe Ala Leu Phe Phe Thr Ile Phe Asp Glu Thr 
            980                 985                 990         


Lys Ser Trp Tyr Phe Thr Glu Asn  Met Glu Arg Asn Cys  Arg Ala Pro 
        995                 1000                 1005             


Cys Asn  Ile Gln Met Glu Asp  Pro Thr Phe Lys Glu  Asn Tyr Arg 
    1010                 1015                 1020             


Phe His  Ala Ile Asn Gly Tyr  Ile Met Asp Thr Leu  Pro Gly Leu 
    1025                 1030                 1035             


Val Met  Ala Gln Asp Gln Arg  Ile Arg Trp Tyr Leu  Leu Ser Met 
    1040                 1045                 1050             


Gly Ser  Asn Glu Asn Ile His  Ser Ile His Phe Ser  Gly His Val 
    1055                 1060                 1065             


Phe Thr  Val Arg Lys Lys Glu  Glu Tyr Lys Met Ala  Leu Tyr Asn 
    1070                 1075                 1080             


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


Ala Gly  Ile Trp Arg Val Glu  Cys Leu Ile Gly Glu  His Leu His 
    1100                 1105                 1110             


Ala Gly  Met Ser Thr Leu Phe  Leu Val Tyr Ser Asn  Lys Cys Gln 
    1115                 1120                 1125             


Thr Pro  Leu Gly Met Ala Ser  Gly His Ile Arg Asp  Phe Gln Ile 
    1130                 1135                 1140             


Thr Ala  Ser Gly Gln Tyr Gly  Gln Trp Ala Pro Lys  Leu Ala Arg 
    1145                 1150                 1155             


Leu His  Tyr Ser Gly Ser Ile  Asn Ala Trp Ser Thr  Lys Glu Pro 
    1160                 1165                 1170             


Phe Ser  Trp Ile Lys Val Asp  Leu Leu Ala Pro Met  Ile Ile His 
    1175                 1180                 1185             


Gly Ile  Lys Thr Gln Gly Ala  Arg Gln Lys Phe Ser  Ser Leu Tyr 
    1190                 1195                 1200             


Ile Ser  Gln Phe Ile Ile Met  Tyr Ser Leu Asp Gly  Lys Lys Trp 
    1205                 1210                 1215             


Gln Thr  Tyr Arg Gly Asn Ser  Thr Gly Thr Leu Met  Val Phe Phe 
    1220                 1225                 1230             


Gly Asn  Val Asp Ser Ser Gly  Ile Lys His Asn Ile  Phe Asn Pro 
    1235                 1240                 1245             


Pro Ile  Ile Ala Arg Tyr Ile  Arg Leu His Pro Thr  His Tyr Ser 
    1250                 1255                 1260             


Ile Arg  Ser Thr Leu Arg Met  Glu Leu Met Gly Cys  Asp Leu Asn 
    1265                 1270                 1275             


Ser Cys  Ser Met Pro Leu Gly  Met Glu Ser Lys Ala  Ile Ser Asp 
    1280                 1285                 1290             


Ala Gln  Ile Thr Ala Ser Ser  Tyr Phe Thr Asn Met  Phe Ala Thr 
    1295                 1300                 1305             


Trp Ser  Pro Ser Lys Ala Arg  Leu His Leu Gln Gly  Arg Ser Asn 
    1310                 1315                 1320             


Ala Trp  Arg Pro Gln Val Asn  Asn Pro Lys Glu Trp  Leu Gln Val 
    1325                 1330                 1335             


Asp Phe  Gln Lys Thr Met Lys  Val Thr Gly Val Thr  Thr Gln Gly 
    1340                 1345                 1350             


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


Ser Ser  Ser Gln Asp Gly His  Gln Trp Thr Leu Phe  Phe Gln Asn 
    1370                 1375                 1380             


Gly Lys  Val Lys Val Phe Gln  Gly Asn Gln Asp Ser  Phe Thr Pro 
    1385                 1390                 1395             


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


Ile His  Pro Gln Ser Trp Val  His Gln Ile Ala Leu  Arg Met Glu 
    1415                 1420                 1425             


Val Leu  Gly Cys Glu Ala Gln  Asp Leu Tyr 
    1430                 1435             


<210>  7
<211>  745
<212>  PRT
<213>  human factor VIII heavy chain (without signal peptide) in hBDDF8

<400>  7

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 
            740                 745 


<210>  8
<211>  13
<212>  PRT
<213>  truncated B-domain in hBDDF8

<400>  8

Ser Phe Ser Gln Asn Pro Pro Val Leu Lys Arg His Gln 
1               5                   10              


<210>  9
<211>  693
<212>  PRT
<213>  human FVIII light chain in hBDDF8

<400>  9

Pro Pro Val Leu Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu 
1               5                   10                  15      


Gln Ser Asp Gln Glu Glu Ile Asp Tyr Asp Asp Thr Ile Ser Val Glu 
            20                  25                  30          


Met Lys Lys Glu Asp Phe Asp Ile Tyr Asp Glu Asp Glu Asn Gln Ser 
        35                  40                  45              


Pro Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val 
    50                  55                  60                  


Glu Arg Leu Trp Asp Tyr Gly Met Ser Ser Ser Pro His Val Leu Arg 
65                  70                  75                  80  


Asn Arg Ala Gln Ser Gly Ser Val Pro Gln Phe Lys Lys Val Val Phe 
                85                  90                  95      


Gln Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu 
            100                 105                 110         


Leu Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val 
        115                 120                 125             


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


Ser Phe Tyr Ser Ser Leu Ile Ser Tyr Glu Glu Asp Gln Arg Gln Gly 
145                 150                 155                 160 


Ala Glu Pro Arg Lys Asn Phe Val Lys Pro Asn Glu Thr Lys Thr Tyr 
                165                 170                 175     


Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp 
            180                 185                 190         


Cys Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val 
        195                 200                 205             


His Ser Gly Leu Ile Gly Pro Leu Leu Val Cys His Thr Asn Thr Leu 
    210                 215                 220                 


Asn Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Phe 
225                 230                 235                 240 


Phe Thr Ile Phe Asp Glu Thr Lys Ser Trp Tyr Phe Thr Glu Asn Met 
                245                 250                 255     


Glu Arg Asn Cys Arg Ala Pro Cys Asn Ile Gln Met Glu Asp Pro Thr 
            260                 265                 270         


Phe Lys Glu Asn Tyr Arg Phe His Ala Ile Asn Gly Tyr Ile Met Asp 
        275                 280                 285             


Thr Leu Pro Gly Leu Val Met Ala Gln Asp Gln Arg Ile Arg Trp Tyr 
    290                 295                 300                 


Leu Leu Ser Met Gly Ser Asn Glu Asn Ile His Ser Ile His Phe Ser 
305                 310                 315                 320 


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


Tyr Asn Leu Tyr Pro Gly Val Phe Glu Thr Val Glu Met Leu Pro Ser 
            340                 345                 350         


Lys Ala Gly Ile Trp Arg Val Glu Cys Leu Ile Gly Glu His Leu His 
        355                 360                 365             


Ala Gly Met Ser Thr Leu Phe Leu Val Tyr Ser Asn Lys Cys Gln Thr 
    370                 375                 380                 


Pro Leu Gly Met Ala Ser Gly His Ile Arg Asp Phe Gln Ile Thr Ala 
385                 390                 395                 400 


Ser Gly Gln Tyr Gly Gln Trp Ala Pro Lys Leu Ala Arg Leu His Tyr 
                405                 410                 415     


Ser Gly Ser Ile Asn Ala Trp Ser Thr Lys Glu Pro Phe Ser Trp Ile 
            420                 425                 430         


Lys Val Asp Leu Leu Ala Pro Met Ile Ile His Gly Ile Lys Thr Gln 
        435                 440                 445             


Gly Ala Arg Gln Lys Phe Ser Ser Leu Tyr Ile Ser Gln Phe Ile Ile 
    450                 455                 460                 


Met Tyr Ser Leu Asp Gly Lys Lys Trp Gln Thr Tyr Arg Gly Asn Ser 
465                 470                 475                 480 


Thr Gly Thr Leu Met Val Phe Phe Gly Asn Val Asp Ser Ser Gly Ile 
                485                 490                 495     


Lys His Asn Ile Phe Asn Pro Pro Ile Ile Ala Arg Tyr Ile Arg Leu 
            500                 505                 510         


His Pro Thr His Tyr Ser Ile Arg Ser Thr Leu Arg Met Glu Leu Met 
        515                 520                 525             


Gly Cys Asp Leu Asn Ser Cys Ser Met Pro Leu Gly Met Glu Ser Lys 
    530                 535                 540                 


Ala Ile Ser Asp Ala Gln Ile Thr Ala Ser Ser Tyr Phe Thr Asn Met 
545                 550                 555                 560 


Phe Ala Thr Trp Ser Pro Ser Lys Ala Arg Leu His Leu Gln Gly Arg 
                565                 570                 575     


Ser Asn Ala Trp Arg Pro Gln Val Asn Asn Pro Lys Glu Trp Leu Gln 
            580                 585                 590         


Val Asp Phe Gln Lys Thr Met Lys Val Thr Gly Val Thr Thr Gln Gly 
        595                 600                 605             


Val Lys Ser Leu Leu Thr Ser Met Tyr Val Lys Glu Phe Leu Ile Ser 
    610                 615                 620                 


Ser Ser Gln Asp Gly His Gln Trp Thr Leu Phe Phe Gln Asn Gly Lys 
625                 630                 635                 640 


Val Lys Val Phe Gln Gly Asn Gln Asp Ser Phe Thr Pro Val Val Asn 
                645                 650                 655     


Ser Leu Asp Pro Pro Leu Leu Thr Arg Tyr Leu Arg Ile His Pro Gln 
            660                 665                 670         


Ser Trp Val His Gln Ile Ala Leu Arg Met Glu Val Leu Gly Cys Glu 
        675                 680                 685             


Ala Gln Asp Leu Tyr 
    690             


<210>  10
<211>  1457
<212>  PRT
<213>  hHC-cLC with signal peptide

<400>  10

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Ser 
        755                 760                 765             


Lys His His Gln Arg Glu Ile Thr Val Thr Thr Leu Gln Pro Glu Glu 
    770                 775                 780                 


Asp Lys Phe Glu Tyr Asp Asp Thr Phe Ser Ile Glu Met Lys Arg Glu 
785                 790                 795                 800 


Asp Phe Asp Ile Tyr Gly Asp Tyr Glu Asn Gln Gly Leu Arg Ser Phe 
                805                 810                 815     


Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp 
            820                 825                 830         


Asp Tyr Gly Met Ser Arg Ser Pro His Ile Leu Arg Asn Arg Ala Gln 
        835                 840                 845             


Ser Gly Asp Val Gln Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr 
    850                 855                 860                 


Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His 
865                 870                 875                 880 


Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val Glu Asp Asn Ile 
                885                 890                 895     


Val Val Thr Phe Lys Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser 
            900                 905                 910         


Ser Leu Ile Ser Tyr Asp Glu Asp Glu Gly Gln Gly Ala Glu Pro Arg 
        915                 920                 925             


Arg Lys Phe Val Asn Pro Asn Glu Thr Lys Ile Tyr Phe Trp Lys Val 
    930                 935                 940                 


Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp 
945                 950                 955                 960 


Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val His Ser Gly Leu 
                965                 970                 975     


Ile Gly Pro Leu Leu Ile Cys Arg Ser Asn Thr Leu Asn Pro Ala His 
            980                 985                 990         


Gly Arg Gln Val Thr Val Gln Glu  Phe Ala Leu Val Phe  Thr Ile Phe 
        995                 1000                 1005             


Asp Glu  Thr Lys Ser Trp Tyr  Phe Thr Glu Asn Leu  Glu Arg Asn 
    1010                 1015                 1020             


Cys Arg  Ala Pro Cys Asn Val  Gln Lys Glu Asp Pro  Thr Leu Lys 
    1025                 1030                 1035             


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


Leu Pro  Gly Leu Val Met Ala  Gln Asp Gln Lys Val  Arg Trp Tyr 
    1055                 1060                 1065             


Leu Leu  Ser Met Gly Ser Asn  Glu Asn Ile His Ser  Ile His Phe 
    1070                 1075                 1080             


Ser Gly  His Val Phe Thr Val  Arg Lys Lys Glu Glu  Tyr Lys Met 
    1085                 1090                 1095             


Ala Val  Tyr Asn Leu Tyr Pro  Gly Val Phe Glu Thr  Val Glu Met 
    1100                 1105                 1110             


Leu Pro  Ser Gln Val Gly Ile  Trp Arg Ile Glu Cys  Leu Ile Gly 
    1115                 1120                 1125             


Glu His  Leu Gln Ala Gly Met  Ser Thr Leu Phe Leu  Val Tyr Ser 
    1130                 1135                 1140             


Lys Lys  Cys Gln Thr Pro Leu  Gly Met Ala Ser Gly  His Ile Arg 
    1145                 1150                 1155             


Asp Phe  Gln Ile Thr Ala Ser  Gly Gln Tyr Gly Gln  Trp Ala Pro 
    1160                 1165                 1170             


Lys Leu  Ala Arg Leu His Tyr  Ser Gly Ser Ile Asn  Ala Trp Ser 
    1175                 1180                 1185             


Thr Lys  Asp Pro Phe Ser Trp  Ile Lys Val Asp Leu  Leu Ala Pro 
    1190                 1195                 1200             


Met Ile  Ile His Gly Ile Met  Thr Gln Gly Ala Arg  Gln Lys Phe 
    1205                 1210                 1215             


Ser Ser  Leu Tyr Val Ser Gln  Phe Ile Ile Met Tyr  Ser Leu Asp 
    1220                 1225                 1230             


Gly Asn  Lys Trp His Ser Tyr  Arg Gly Asn Ser Thr  Gly Thr Leu 
    1235                 1240                 1245             


Met Val  Phe Phe Gly Asn Val  Asp Ser Ser Gly Ile  Lys His Asn 
    1250                 1255                 1260             


Ile Phe  Asn Pro Pro Ile Ile  Ala Gln Tyr Ile Arg  Leu His Pro 
    1265                 1270                 1275             


Thr His  Tyr Ser Ile Arg Ser  Thr Leu Arg Met Glu  Leu Leu Gly 
    1280                 1285                 1290             


Cys Asp  Phe Asn Ser Cys Ser  Met Pro Leu Gly Met  Glu Ser Lys 
    1295                 1300                 1305             


Ala Ile  Ser Asp Ala Gln Ile  Thr Ala Ser Ser Tyr  Leu Ser Ser 
    1310                 1315                 1320             


Met Leu  Ala Thr Trp Ser Pro  Ser Gln Ala Arg Leu  His Leu Gln 
    1325                 1330                 1335             


Gly Arg  Thr Asn Ala Trp Arg  Pro Gln Ala Asn Asn  Pro Lys Glu 
    1340                 1345                 1350             


Trp Leu  Gln Val Asp Phe Arg  Lys Thr Met Lys Val  Thr Gly Ile 
    1355                 1360                 1365             


Thr Thr  Gln Gly Val Lys Ser  Leu Leu Ile Ser Met  Tyr Val Lys 
    1370                 1375                 1380             


Glu Phe  Leu Ile Ser Ser Ser  Gln Asp Gly His Asn  Trp Thr Leu 
    1385                 1390                 1395             


Phe Leu  Gln Asn Gly Lys Val  Lys Val Phe Gln Gly  Asn Arg Asp 
    1400                 1405                 1410             


Ser Ser  Thr Pro Val Arg Asn  Ala Leu Glu Pro Pro  Leu Val Ala 
    1415                 1420                 1425             


Arg Tyr  Val Arg Leu His Pro  Gln Ser Trp Ala His  His Ile Ala 
    1430                 1435                 1440             


Leu Arg  Leu Glu Val Leu Gly  Cys Asp Thr Gln Gln  Pro Ala 
    1445                 1450                 1455         


<210>  11
<211>  4374
<212>  DNA
<213>  cDNA of hHC-cLC

<400>  11
atgcaaatag agctctccac ctgcttcttt ctgtgccttt tgcgattctg ctttagtgcc       60

accagaagat actacctggg tgcagtggaa ctgtcatggg actatatgca aagtgatctc      120

ggtgagctgc ctgtggacgc aagatttcct cctagagtgc caaaatcttt tccattcaac      180

acctcagtcg tgtacaaaaa gactctgttt gtagaattca cggatcacct tttcaacatc      240

gctaagccaa ggccaccctg gatgggtctg ctaggtccta ccatccaggc tgaggtttat      300

gatacagtgg tcattacact taagaacatg gcttcccatc ctgtcagtct tcatgctgtt      360

ggtgtatcct actggaaagc ttctgaggga gctgaatatg atgatcagac cagtcaaagg      420

gagaaagaag atgataaagt cttccctggt ggaagccata catatgtctg gcaggtcctg      480

aaagagaatg gtccaatggc ctctgaccca ctgtgcctta cctactcata tctttctcat      540

gtggacctgg taaaagactt gaattcaggc ctcattggag ccctactagt atgtagagaa      600

gggagtctgg ccaaggaaaa gacacagacc ttgcacaaat ttatactact ttttgctgta      660

tttgatgaag ggaaaagttg gcactcagaa acaaagaact ccttgatgca ggatagggat      720

gctgcatctg ctcgtgcctg gcctaaaatg cacacagtca atggttatgt aaacaggtct      780

ctgccaggtc tgattggatg ccacaggaaa tcagtctatt ggcatgtgat tggaatgggc      840

accactcctg aagtgcactc aatattcctc gaaggtcaca catttcttgt gaggaaccat      900

cgccaggcgt ccttggaaat ctcgccaata actttcctta ctgctcaaac actcttgatg      960

gaccttggac agtttctact gttttgtcat atctcttccc accaacatga tggcatggaa     1020

gcttatgtca aagtagacag ctgtccagag gaaccccaac tacgaatgaa aaataatgaa     1080

gaagcggaag actatgatga tgatcttact gattctgaaa tggatgtggt caggtttgat     1140

gatgacaact ctccttcctt tatccaaatt cgctcagttg ccaagaagca tcctaaaact     1200

tgggtacatt acattgctgc tgaagaggag gactgggact atgctccctt agtcctcgcc     1260

cccgatgaca gaagttataa aagtcaatat ttgaacaatg gccctcagcg gattggtagg     1320

aagtacaaaa aagtccgatt tatggcatac acagatgaaa cctttaagac tcgtgaagct     1380

attcagcatg aatcaggaat cttgggacct ttactttatg gggaagttgg agacacactg     1440

ttgattatat ttaagaatca agcaagcaga ccatataaca tctaccctca cggaatcact     1500

gatgtccgtc ctttgtattc aaggagatta ccaaaaggtg taaaacattt gaaggatttt     1560

ccaattctgc caggagaaat attcaaatat aaatggacag tgactgtaga agatgggcca     1620

actaaatcag atcctcggtg cctgacccgc tattactcta gtttcgttaa tatggagaga     1680

gatctagctt caggactcat tggccctctc ctcatctgct acaaagaatc tgtagatcaa     1740

agaggaaacc agataatgtc agacaagagg aatgtcatcc tgttttctgt atttgatgag     1800

aaccgaagct ggtacctcac agagaatata caacgctttc tccccaatcc agctggagtg     1860

cagcttgagg atccagagtt ccaagcctcc aacatcatgc acagcatcaa tggctatgtt     1920

tttgatagtt tgcagttgtc agtttgtttg catgaggtgg catactggta cattctaagc     1980

attggagcac agactgactt cctttctgtc ttcttctctg gatatacctt caaacacaaa     2040

atggtctatg aagacacact caccctattc ccattctcag gagaaactgt cttcatgtcg     2100

atggaaaacc caggtctatg gattctgggg tgccacaact cagactttcg gaacagaggc     2160

atgaccgcct tactgaaggt ttctagttgt gacaagaaca ctggtgatta ttacgaggac     2220

agttatgaag atatttcagc atacttgctg agtaaaaaca atgccattga accaagaagc     2280

ttctcccaga atccaccagt ctcaaaacac catcaaaggg aaataaccgt tactactctt     2340

cagccagagg aagacaaatt tgagtatgat gacaccttct caattgaaat gaagagagaa     2400

gattttgaca tctacggcga ctatgaaaat cagggcctcc gcagctttca aaagaaaaca     2460

cgacactatt tcattgctgc agtggagcgt ctctgggatt atgggatgag tagatctccc     2520

catatactaa gaaacagggc tcaaagtggg gatgtccagc agttcaagaa ggtggttttc     2580

caggaattta ctgatggatc ctttactcag cccttatacc gtggagaact gaatgaacac     2640

ttgggactct tggggccata tataagagca gaagttgaag acaatatcgt ggtaactttc     2700

aaaaaccagg cctctcgtcc ctactccttc tattctagtc ttatttctta tgacgaagat     2760

gagggacaag gagcagaacc tagaagaaag tttgtcaacc ctaatgaaac caaaatttac     2820

ttttggaaag tgcagcatca tatggcaccc actaaagatg agtttgactg caaagcctgg     2880

gcttattttt ctgatgttga tttggagaaa gatgtgcact caggcttgat tggacccctt     2940

ctgatctgcc gcagtaacac actgaaccct gctcatggga gacaagtgac agtgcaggag     3000

tttgccctgg ttttcactat attcgatgag actaagagct ggtacttcac tgaaaacctg     3060

gaaaggaact gtagagctcc ctgcaatgtc cagaaggagg accctactct aaaagaaaac     3120

ttccgcttcc atgcaatcaa cggctatgtg aaggatacac tccctggctt agtaatggct     3180

caggatcaaa aggttcgatg gtatctgctc agcatgggca gcaacgaaaa cattcattcc     3240

attcacttca gtggacatgt gttcactgta cggaaaaaag aggaatataa aatggcagtc     3300

tacaacctct atccaggtgt ttttgagact gtggaaatgc taccatccca agttggaatc     3360

tggcggatag aatgccttat cggcgagcac ctgcaagccg ggatgagcac tctgtttctg     3420

gtgtacagca agaagtgtca gactccactg gggatggctt ccggacacat tagagatttt     3480

cagattacag cttcaggaca atatggacag tgggccccaa agctggccag acttcattat     3540

tccggatcaa tcaatgcctg gagcaccaag gatccctttt cctggatcaa ggtggatctc     3600

ttggcaccga tgattattca cggcatcatg acccaggggg cccgccagaa gttctccagc     3660

ctctacgtgt ctcagtttat catcatgtac agtctggatg gcaacaagtg gcacagttac     3720

cgagggaatt ccacggggac cttaatggtc ttctttggca acgtggattc atctgggatc     3780

aaacacaata tttttaaccc tccgattatt gctcagtaca tccgtttgca cccaacccat     3840

tacagcatcc gcagcactct tcgcatggag ctcttgggct gtgacttcaa cagttgcagc     3900

atgccgctgg ggatggagag taaagcaata tcagatgctc agatcactgc ctcgtcctac     3960

ctaagcagta tgcttgccac ttggtctcct tcccaagccc ggctgcacct gcagggcagg     4020

actaatgcct ggagacctca ggcaaataac ccaaaagagt ggctgcaagt ggacttccgg     4080

aagaccatga aagtcacagg aataaccacc cagggggtga aatctctcct catcagcatg     4140

tatgtgaagg agttcctcat ctccagtagt caagatggcc ataactggac tctgtttctt     4200

cagaatggca aagtcaaggt cttccaggga aaccgggact cctccacgcc tgtgcggaac     4260

gctctcgaac ccccgctggt ggctcgctac gtgcgcctgc acccgcagag ctgggcgcac     4320

cacatcgccc tgaggctgga ggtcctgggc tgcgacaccc agcagcccgc ctga           4374


<210>  12
<211>  1438
<212>  PRT
<213>  hHC-cLC without signal peptide

<400>  12

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 Pro Pro Val Ser Lys His His 
            740                 745                 750         


Gln Arg Glu Ile Thr Val Thr Thr Leu Gln Pro Glu Glu Asp Lys Phe 
        755                 760                 765             


Glu Tyr Asp Asp Thr Phe Ser Ile Glu Met Lys Arg Glu Asp Phe Asp 
    770                 775                 780                 


Ile Tyr Gly Asp Tyr Glu Asn Gln Gly Leu Arg Ser Phe Gln Lys Lys 
785                 790                 795                 800 


Thr Arg His Tyr Phe Ile Ala Ala Val Glu Arg Leu Trp Asp Tyr Gly 
                805                 810                 815     


Met Ser Arg Ser Pro His Ile Leu Arg Asn Arg Ala Gln Ser Gly Asp 
            820                 825                 830         


Val Gln Gln Phe Lys Lys Val Val Phe Gln Glu Phe Thr Asp Gly Ser 
        835                 840                 845             


Phe Thr Gln Pro Leu Tyr Arg Gly Glu Leu Asn Glu His Leu Gly Leu 
    850                 855                 860                 


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


Phe Lys Asn Gln Ala Ser Arg Pro Tyr Ser Phe Tyr Ser Ser Leu Ile 
                885                 890                 895     


Ser Tyr Asp Glu Asp Glu Gly Gln Gly Ala Glu Pro Arg Arg Lys Phe 
            900                 905                 910         


Val Asn Pro Asn Glu Thr Lys Ile Tyr Phe Trp Lys Val Gln His His 
        915                 920                 925             


Met Ala Pro Thr Lys Asp Glu Phe Asp Cys Lys Ala Trp Ala Tyr Phe 
    930                 935                 940                 


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


Leu Leu Ile Cys Arg Ser Asn Thr Leu Asn Pro Ala His Gly Arg Gln 
                965                 970                 975     


Val Thr Val Gln Glu Phe Ala Leu Val Phe Thr Ile Phe Asp Glu Thr 
            980                 985                 990         


Lys Ser Trp Tyr Phe Thr Glu Asn  Leu Glu Arg Asn Cys  Arg Ala Pro 
        995                 1000                 1005             


Cys Asn  Val Gln Lys Glu Asp  Pro Thr Leu Lys Glu  Asn Phe Arg 
    1010                 1015                 1020             


Phe His  Ala Ile Asn Gly Tyr  Val Lys Asp Thr Leu  Pro Gly Leu 
    1025                 1030                 1035             


Val Met  Ala Gln Asp Gln Lys  Val Arg Trp Tyr Leu  Leu Ser Met 
    1040                 1045                 1050             


Gly Ser  Asn Glu Asn Ile His  Ser Ile His Phe Ser  Gly His Val 
    1055                 1060                 1065             


Phe Thr  Val Arg Lys Lys Glu  Glu Tyr Lys Met Ala  Val Tyr Asn 
    1070                 1075                 1080             


Leu Tyr  Pro Gly Val Phe Glu  Thr Val Glu Met Leu  Pro Ser Gln 
    1085                 1090                 1095             


Val Gly  Ile Trp Arg Ile Glu  Cys Leu Ile Gly Glu  His Leu Gln 
    1100                 1105                 1110             


Ala Gly  Met Ser Thr Leu Phe  Leu Val Tyr Ser Lys  Lys Cys Gln 
    1115                 1120                 1125             


Thr Pro  Leu Gly Met Ala Ser  Gly His Ile Arg Asp  Phe Gln Ile 
    1130                 1135                 1140             


Thr Ala  Ser Gly Gln Tyr Gly  Gln Trp Ala Pro Lys  Leu Ala Arg 
    1145                 1150                 1155             


Leu His  Tyr Ser Gly Ser Ile  Asn Ala Trp Ser Thr  Lys Asp Pro 
    1160                 1165                 1170             


Phe Ser  Trp Ile Lys Val Asp  Leu Leu Ala Pro Met  Ile Ile His 
    1175                 1180                 1185             


Gly Ile  Met Thr Gln Gly Ala  Arg Gln Lys Phe Ser  Ser Leu Tyr 
    1190                 1195                 1200             


Val Ser  Gln Phe Ile Ile Met  Tyr Ser Leu Asp Gly  Asn Lys Trp 
    1205                 1210                 1215             


His Ser  Tyr Arg Gly Asn Ser  Thr Gly Thr Leu Met  Val Phe Phe 
    1220                 1225                 1230             


Gly Asn  Val Asp Ser Ser Gly  Ile Lys His Asn Ile  Phe Asn Pro 
    1235                 1240                 1245             


Pro Ile  Ile Ala Gln Tyr Ile  Arg Leu His Pro Thr  His Tyr Ser 
    1250                 1255                 1260             


Ile Arg  Ser Thr Leu Arg Met  Glu Leu Leu Gly Cys  Asp Phe Asn 
    1265                 1270                 1275             


Ser Cys  Ser Met Pro Leu Gly  Met Glu Ser Lys Ala  Ile Ser Asp 
    1280                 1285                 1290             


Ala Gln  Ile Thr Ala Ser Ser  Tyr Leu Ser Ser Met  Leu Ala Thr 
    1295                 1300                 1305             


Trp Ser  Pro Ser Gln Ala Arg  Leu His Leu Gln Gly  Arg Thr Asn 
    1310                 1315                 1320             


Ala Trp  Arg Pro Gln Ala Asn  Asn Pro Lys Glu Trp  Leu Gln Val 
    1325                 1330                 1335             


Asp Phe  Arg Lys Thr Met Lys  Val Thr Gly Ile Thr  Thr Gln Gly 
    1340                 1345                 1350             


Val Lys  Ser Leu Leu Ile Ser  Met Tyr Val Lys Glu  Phe Leu Ile 
    1355                 1360                 1365             


Ser Ser  Ser Gln Asp Gly His  Asn Trp Thr Leu Phe  Leu Gln Asn 
    1370                 1375                 1380             


Gly Lys  Val Lys Val Phe Gln  Gly Asn Arg Asp Ser  Ser Thr Pro 
    1385                 1390                 1395             


Val Arg  Asn Ala Leu Glu Pro  Pro Leu Val Ala Arg  Tyr Val Arg 
    1400                 1405                 1410             


Leu His  Pro Gln Ser Trp Ala  His His Ile Ala Leu  Arg Leu Glu 
    1415                 1420                 1425             


Val Leu  Gly Cys Asp Thr Gln  Gln Pro Ala 
    1430                 1435             


<210>  13
<211>  13
<212>  PRT
<213>  truncated B-domain in hHC-cLC

<400>  13

Ser Phe Ser Gln Asn Pro Pro Val Ser Lys His His Gln 
1               5                   10              


<210>  14
<211>  693
<212>  PRT
<213>  canine FVIII light chain in hHC-cLC

<400>  14

Pro Pro Val Ser Lys His His Gln Arg Glu Ile Thr Val Thr Thr Leu 
1               5                   10                  15      


Gln Pro Glu Glu Asp Lys Phe Glu Tyr Asp Asp Thr Phe Ser Ile Glu 
            20                  25                  30          


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


Leu Arg Ser Phe Gln Lys Lys Thr Arg His Tyr Phe Ile Ala Ala Val 
    50                  55                  60                  


Glu Arg Leu Trp Asp Tyr Gly Met Ser Arg Ser Pro His Ile Leu Arg 
65                  70                  75                  80  


Asn Arg Ala Gln Ser Gly Asp Val Gln Gln Phe Lys Lys Val Val Phe 
                85                  90                  95      


Gln Glu Phe Thr Asp Gly Ser Phe Thr Gln Pro Leu Tyr Arg Gly Glu 
            100                 105                 110         


Leu Asn Glu His Leu Gly Leu Leu Gly Pro Tyr Ile Arg Ala Glu Val 
        115                 120                 125             


Glu Asp Asn Ile Val Val Thr Phe Lys Asn Gln Ala Ser Arg Pro Tyr 
    130                 135                 140                 


Ser Phe Tyr Ser Ser Leu Ile Ser Tyr Asp Glu Asp Glu Gly Gln Gly 
145                 150                 155                 160 


Ala Glu Pro Arg Arg Lys Phe Val Asn Pro Asn Glu Thr Lys Ile Tyr 
                165                 170                 175     


Phe Trp Lys Val Gln His His Met Ala Pro Thr Lys Asp Glu Phe Asp 
            180                 185                 190         


Cys Lys Ala Trp Ala Tyr Phe Ser Asp Val Asp Leu Glu Lys Asp Val 
        195                 200                 205             


His Ser Gly Leu Ile Gly Pro Leu Leu Ile Cys Arg Ser Asn Thr Leu 
    210                 215                 220                 


Asn Pro Ala His Gly Arg Gln Val Thr Val Gln Glu Phe Ala Leu Val 
225                 230                 235                 240 


Phe Thr Ile Phe Asp Glu Thr Lys Ser Trp Tyr Phe Thr Glu Asn Leu 
                245                 250                 255     


Glu Arg Asn Cys Arg Ala Pro Cys Asn Val Gln Lys Glu Asp Pro Thr 
            260                 265                 270         


Leu Lys Glu Asn Phe Arg Phe His Ala Ile Asn Gly Tyr Val Lys Asp 
        275                 280                 285             


Thr Leu Pro Gly Leu Val Met Ala Gln Asp Gln Lys Val Arg Trp Tyr 
    290                 295                 300                 


Leu Leu Ser Met Gly Ser Asn Glu Asn Ile His Ser Ile His Phe Ser 
305                 310                 315                 320 


Gly His Val Phe Thr Val Arg Lys Lys Glu Glu Tyr Lys Met Ala Val 
                325                 330                 335     


Tyr Asn Leu Tyr Pro Gly Val Phe Glu Thr Val Glu Met Leu Pro Ser 
            340                 345                 350         


Gln Val Gly Ile Trp Arg Ile Glu Cys Leu Ile Gly Glu His Leu Gln 
        355                 360                 365             


Ala Gly Met Ser Thr Leu Phe Leu Val Tyr Ser Lys Lys Cys Gln Thr 
    370                 375                 380                 


Pro Leu Gly Met Ala Ser Gly His Ile Arg Asp Phe Gln Ile Thr Ala 
385                 390                 395                 400 


Ser Gly Gln Tyr Gly Gln Trp Ala Pro Lys Leu Ala Arg Leu His Tyr 
                405                 410                 415     


Ser Gly Ser Ile Asn Ala Trp Ser Thr Lys Asp Pro Phe Ser Trp Ile 
            420                 425                 430         


Lys Val Asp Leu Leu Ala Pro Met Ile Ile His Gly Ile Met Thr Gln 
        435                 440                 445             


Gly Ala Arg Gln Lys Phe Ser Ser Leu Tyr Val Ser Gln Phe Ile Ile 
    450                 455                 460                 


Met Tyr Ser Leu Asp Gly Asn Lys Trp His Ser Tyr Arg Gly Asn Ser 
465                 470                 475                 480 


Thr Gly Thr Leu Met Val Phe Phe Gly Asn Val Asp Ser Ser Gly Ile 
                485                 490                 495     


Lys His Asn Ile Phe Asn Pro Pro Ile Ile Ala Gln Tyr Ile Arg Leu 
            500                 505                 510         


His Pro Thr His Tyr Ser Ile Arg Ser Thr Leu Arg Met Glu Leu Leu 
        515                 520                 525             


Gly Cys Asp Phe Asn Ser Cys Ser Met Pro Leu Gly Met Glu Ser Lys 
    530                 535                 540                 


Ala Ile Ser Asp Ala Gln Ile Thr Ala Ser Ser Tyr Leu Ser Ser Met 
545                 550                 555                 560 


Leu Ala Thr Trp Ser Pro Ser Gln Ala Arg Leu His Leu Gln Gly Arg 
                565                 570                 575     


Thr Asn Ala Trp Arg Pro Gln Ala Asn Asn Pro Lys Glu Trp Leu Gln 
            580                 585                 590         


Val Asp Phe Arg Lys Thr Met Lys Val Thr Gly Ile Thr Thr Gln Gly 
        595                 600                 605             


Val Lys Ser Leu Leu Ile Ser Met Tyr Val Lys Glu Phe Leu Ile Ser 
    610                 615                 620                 


Ser Ser Gln Asp Gly His Asn Trp Thr Leu Phe Leu Gln Asn Gly Lys 
625                 630                 635                 640 


Val Lys Val Phe Gln Gly Asn Arg Asp Ser Ser Thr Pro Val Arg Asn 
                645                 650                 655     


Ala Leu Glu Pro Pro Leu Val Ala Arg Tyr Val Arg Leu His Pro Gln 
            660                 665                 670         


Ser Trp Ala His His Ile Ala Leu Arg Leu Glu Val Leu Gly Cys Asp 
        675                 680                 685             


Thr Gln Gln Pro Ala 
    690             


<210>  15
<211>  9618
<212>  DNA
<213>  pANG-CAG-hBDDF8

<400>  15
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtgccaac tccatcacta      120

ggggttcctt gtagttaatg attaacccgc catgctactt atttacgtag ccatgctcta      180

ggtaccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca      240

ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta      300

tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta      360

tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat      420

cgctattacc atgtcgaggc cacgttctgc ttcactctcc ccatctcccc cccctcccca      480

cccccaattt tgtatttatt tattttttaa ttattttgtg cagcgatggg ggcggggggg      540

gggggcgcgc gccaggcggg gcggggcggg gcgaggggcg gggcggggcg aggcggagag      600

gtgcggcggc agccaatcag agcggcgcgc tccgaaagtt tccttttatg gcgaggcggc      660

ggcggcggcg gccctataaa aagcgaagcg cgcggcgggc gggagcaagc tctagccgcg      720

cggcgggcgg gagtcgctgc gcgctgcctt cgccccgtgc cccgctccgc cgccgcctcg      780

cgccgcccgc cccggctctg actgaccgcg ttactcccac aggtgagcgg gcgggacggc      840

ccttctcctc cgggctgtaa ttagcgcttg gtttaatgac ggcttgtttc ttttctgtgg      900

ctgcgtgaaa gccttgaggg gctccgggag ggccctttgt gcggggggag cggctcgggg      960

ctgtccgcgg ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg     1020

gcgtgtgacc ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct     1080

acagctcctg ggcaacgtgc tggttattgt gctgtctcat cattttggca aagaattgat     1140

ccacactttt tctttttctc cacaggtatc gattccacca tgcaaataga gctctccacc     1200

tgcttctttc tgtgcctttt gcgattctgc tttagtgcca ccagaagata ctacctgggt     1260

gcagtggaac tgtcatggga ctatatgcaa agtgatctcg gtgagctgcc tgtggacgca     1320

agatttcctc ctagagtgcc aaaatctttt ccattcaaca cctcagtcgt gtacaaaaag     1380

actctgtttg tagaattcac ggatcacctt ttcaacatcg ctaagccaag gccaccctgg     1440

atgggtctgc taggtcctac catccaggct gaggtttatg atacagtggt cattacactt     1500

aagaacatgg cttcccatcc tgtcagtctt catgctgttg gtgtatccta ctggaaagct     1560

tctgagggag ctgaatatga tgatcagacc agtcaaaggg agaaagaaga tgataaagtc     1620

ttccctggtg gaagccatac atatgtctgg caggtcctga aagagaatgg tccaatggcc     1680

tctgacccac tgtgccttac ctactcatat ctttctcatg tggacctggt aaaagacttg     1740

aattcaggcc tcattggagc cctactagta tgtagagaag ggagtctggc caaggaaaag     1800

acacagacct tgcacaaatt tatactactt tttgctgtat ttgatgaagg gaaaagttgg     1860

cactcagaaa caaagaactc cttgatgcag gatagggatg ctgcatctgc tcgggcctgg     1920

cctaaaatgc acacagtcaa tggttatgta aacaggtctc tgccaggtct gattggatgc     1980

cacaggaaat cagtctattg gcatgtgatt ggaatgggca ccactcctga agtgcactca     2040

atattcctcg aaggtcacac atttcttgtg aggaaccatc gccaggcgtc cttggaaatc     2100

tcgccaataa ctttccttac tgctcaaaca ctcttgatgg accttggaca gtttctactg     2160

ttttgtcata tctcttccca ccaacatgat ggcatggaag cttatgtcaa agtagacagc     2220

tgtccagagg aaccccaact acgaatgaaa aataatgaag aagcggaaga ctatgatgat     2280

gatcttactg attctgaaat ggatgtggtc aggtttgatg atgacaactc tccttccttt     2340

atccaaattc gctcagttgc caagaagcat cctaaaactt gggtacatta cattgctgct     2400

gaagaggagg actgggacta tgctccctta gtcctcgccc ccgatgacag aagttataaa     2460

agtcaatatt tgaacaatgg ccctcagcgg attggtagga agtacaaaaa agtccgattt     2520

atggcataca cagatgaaac ctttaagact cgtgaagcta ttcagcatga atcaggaatc     2580

ttgggacctt tactttatgg ggaagttgga gacacactgt tgattatatt taagaatcaa     2640

gcaagcagac catataacat ctaccctcac ggaatcactg atgtccgtcc tttgtattca     2700

aggagattac caaaaggtgt aaaacatttg aaggattttc caattctgcc aggagaaata     2760

ttcaaatata aatggacagt gactgtagaa gatgggccaa ctaaatcaga tcctcggtgc     2820

ctgacccgct attactctag tttcgttaat atggagagag atctagcttc aggactcatt     2880

ggccctctcc tcatctgcta caaagaatct gtagatcaaa gaggaaacca gataatgtca     2940

gacaagagga atgtcatcct gttttctgta tttgatgaga accgaagctg gtacctcaca     3000

gagaatatac aacgctttct ccccaatcca gctggagtgc agcttgagga tccagagttc     3060

caagcctcca acatcatgca cagcatcaat ggctatgttt ttgatagttt gcagttgtca     3120

gtttgtttgc atgaggtggc atactggtac attctaagca ttggagcaca gactgacttc     3180

ctttctgtct tcttctctgg atataccttc aaacacaaaa tggtctatga agacacactc     3240

accctattcc cattctcagg agaaactgtc ttcatgtcga tggaaaaccc aggtctatgg     3300

attctggggt gccacaactc agactttcgg aacagaggca tgaccgcctt actgaaggtt     3360

tctagttgtg acaagaacac tggtgattat tacgaggaca gttatgaaga tatttcagca     3420

tacttgctga gtaaaaacaa tgccattgaa ccaagaagct tctcccagaa tccaccagtc     3480

ttgaaacgcc atcaacgcga aataactcgt actactcttc agtcagatca agaggaaatt     3540

gactatgatg ataccatatc agttgaaatg aagaaggaag attttgacat ttatgatgag     3600

gatgaaaatc agagcccccg cagctttcaa aagaaaacac gacactattt tattgctgca     3660

gtggagaggc tctgggatta tgggatgagt agctccccac atgttctaag aaacagggct     3720

cagagtggca gtgtccctca gttcaagaaa gttgttttcc aggaatttac tgatggctcc     3780

tttactcagc ccttataccg tggagaacta aatgaacatt tgggactcct ggggccatat     3840

ataagagcag aagttgaaga taatatcatg gtaactttca gaaatcaggc ctctcgtccc     3900

tattccttct attctagcct tatttcttat gaggaagatc agaggcaagg agcagaacct     3960

agaaaaaact ttgtcaagcc taatgaaacc aaaacttact tttggaaagt gcaacatcat     4020

atggcaccca ctaaagatga gtttgactgc aaagcctggg cttatttctc tgatgttgac     4080

ctggaaaaag atgtgcactc aggcctgatt ggaccccttc tggtctgcca cactaacaca     4140

ctgaaccctg ctcatgggag acaagtgaca gtacaggaat ttgctctgtt tttcaccatc     4200

tttgatgaga ccaaaagctg gtacttcact gaaaatatgg aaagaaactg cagggctccc     4260

tgcaatatcc agatggaaga tcccactttt aaagagaatt atcgcttcca tgcaatcaat     4320

ggctacataa tggatacact acctggctta gtaatggctc aggatcaaag gattcgatgg     4380

tatctgctca gcatgggcag caatgaaaac atccattcta ttcatttcag tggacatgtg     4440

ttcactgtac gaaaaaaaga ggagtataaa atggcactgt acaatctcta tccaggtgtt     4500

tttgagacag tggaaatgtt accatccaaa gctggaattt ggcgggtgga atgccttatt     4560

ggcgagcatc tacatgctgg gatgagcaca ctttttctgg tgtacagcaa taagtgtcag     4620

actcccctgg gaatggcttc tggacacatt agagattttc agattacagc ttcaggacaa     4680

tatggacagt gggccccaaa gctggccaga cttcattatt ccggatcaat caatgcctgg     4740

agcaccaagg agcccttttc ttggatcaag gtggatctgt tggcaccaat gattattcac     4800

ggcatcaaga cccagggtgc ccgtcagaag ttctccagcc tctacatctc tcagtttatc     4860

atcatgtata gtcttgatgg gaagaagtgg cagacttatc gaggaaattc cactggaacc     4920

ttaatggtct tctttggcaa tgtggattca tctgggataa aacacaatat ttttaaccct     4980

ccaattattg ctcgatacat ccgtttgcac ccaactcatt atagcattcg cagcactctt     5040

cgcatggagt tgatgggctg tgatttaaat agttgcagca tgccattggg aatggagagt     5100

aaagcaatat cagatgcaca gattactgct tcatcctact ttaccaatat gtttgccacc     5160

tggtctcctt caaaagctcg acttcacctc caagggagga gtaatgcctg gagacctcag     5220

gtgaataatc caaaagagtg gctgcaagtg gacttccaga agacaatgaa agtcacagga     5280

gtaactactc agggagtaaa atctctgctt accagcatgt atgtgaagga gttcctcatc     5340

tccagcagtc aagatggcca tcagtggact ctcttttttc agaatggcaa agtaaaggtt     5400

tttcagggaa atcaagactc cttcacacct gtggtgaact ctctagaccc accgttactg     5460

actcgctacc ttcgaattca cccccagagt tgggtgcacc agattgccct gaggatggag     5520

gttctgggct gcgaggcaca ggacctctac tgactcgaga ataaaagatc agagctctag     5580

agatctgtgt gttggttttt tgtgtgcggc cgggatctga ggaaccccta gtgatggagt     5640

tggccactcc ctctctgcgc gctcgctcgc tcactgaggc cgcccgggca aagcccgggc     5700

gtcgggcgac ctttggtcgc ccggcctcag tgagcgagcg agcgcgcaga gagggagtgg     5760

ccaacccccc cccccccccc cctgcaggcg attctcttgt ttgctccaga ctctcaggca     5820

atgacctgat agcctttgta gagacctctc aaaaatagct accctctccg gcatgaattt     5880

atcagctaga acggttgaat atcatattga tggtgatttg actgtctccg gcctttctca     5940

cccgtttgaa tctttaccta cacattactc aggcattgca tttaaaatat atgagggttc     6000

taaaaatttt tatccttgcg ttgaaataaa ggcttctccc gcaaaagtat tacagggtca     6060

taatgttttt ggtacaaccg atttagcttt atgctctgag gctttattgc ttaattttgc     6120

taattctttg ccttgcctgt atgatttatt ggatgttgga attcctgatg cggtattttc     6180

tccttacgca tctgtgcggt atttcacacc gcatatggtg cactctcagt acaatctgct     6240

ctgatgccgc atagttaagc cagccccgac acccgccaac acccgctgac gcgccctgac     6300

gggcttgtct gctcccggca tccgcttaca gacaagctgt gaccgtctcc gggagctgca     6360

tgtgtcagag gttttcaccg tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac     6420

gcctattttt ataggttaat gtcatgataa taatggtttc ttagacgtca ggtggcactt     6480

ttcggggaaa tgtgcgcgga acccctattt gtttattttt ctaaatacat tcaaatatgt     6540

atccgctcat gagacaataa ccctgataaa tgcttcaata atattgaaaa aggaagagta     6600

tgagtattca acatttccgt gtcgccctta ttcccttttt tgcggcattt tgccttcctg     6660

tttttgctca cccagaaacg ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac     6720

gagtgggtta catcgaactg gatctcaaca gcggtaagat ccttgagagt tttcgccccg     6780

aagaacgttt tccaatgatg agcactttta aagttctgct atgtggcgcg gtattatccc     6840

gtattgacgc cgggcaagag caactcggtc gccgcataca ctattctcag aatgacttgg     6900

ttgagtactc accagtcaca gaaaagcatc ttacggatgg catgacagta agagaattat     6960

gcagtgctgc cataaccatg agtgataaca ctgcggccaa cttacttctg acaacgatcg     7020

gaggaccgaa ggagctaacc gcttttttgc acaacatggg ggatcatgta actcgccttg     7080

atcgttggga accggagctg aatgaagcca taccaaacga cgagcgtgac accacgatgc     7140

ctgtagcaat ggcaacaacg ttgcgcaaac tattaactgg cgaactactt actctagctt     7200

cccggcaaca attaatagac tggatggagg cggataaagt tgcaggacca cttctgcgct     7260

cggcccttcc ggctggctgg tttattgctg ataaatctgg agccggtgag cgtgggtctc     7320

gcggtatcat tgcagcactg gggccagatg gtaagccctc ccgtatcgta gttatctaca     7380

cgacggggag tcaggcaact atggatgaac gaaatagaca gatcgctgag ataggtgcct     7440

cactgattaa gcattggtaa ctgtcagacc aagtttactc atatatactt tagattgatt     7500

taaaacttca tttttaattt aaaaggatct aggtgaagat cctttttgat aatctcatga     7560

ccaaaatccc ttaacgtgag ttttcgttcc actgagcgtc agaccccgta gaaaagatca     7620

aaggatcttc ttgagatcct ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac     7680

caccgctacc agcggtggtt tgtttgccgg atcaagagct accaactctt tttccgaagg     7740

taactggctt cagcagagcg cagataccaa atactgtcct tctagtgtag ccgtagttag     7800

gccaccactt caagaactct gtagcaccgc ctacatacct cgctctgcta atcctgttac     7860

cagtggctgc tgccagtggc gataagtcgt gtcttaccgg gttggactca agacgatagt     7920

taccggataa ggcgcagcgg tcgggctgaa cggggggttc gtgcacacag cccagcttgg     7980

agcgaacgac ctacaccgaa ctgagatacc tacagcgtga gctatgagaa agcgccacgc     8040

ttcccgaagg gagaaaggcg gacaggtatc cggtaagcgg cagggtcgga acaggagagc     8100

gcacgaggga gcttccaggg ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc     8160

acctctgact tgagcgtcga tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa     8220

acgccagcaa cgcggccttt ttacggttcc tggccttttg ctggcctttt gctcacatgt     8280

tctttcctgc gttatcccct gattctgtgg ataaccgtat taccgccttt gagtgagctg     8340

ataccgctcg ccgcagccga acgaccgagc gcagcgagtc agtgagcgag gaagcggaag     8400

agcgcccaat acgcaaaccg cctctccccg cgcgttggcc gattcattaa tgcagaattc     8460

ccatcatcaa taatatacct tattttggat tgaagccaat atgataatga gggggtggag     8520

tttgtgacgt ggcgcggggc gtgggaacgg ggcgggtgac gtagtagtct ctagaggtcc     8580

ccagcgacct tgacgggcat ctgcccggca tttctgacag ctttgtgaac tgggtggccg     8640

agaaggaatg ggagttgccg ccagattctg acatggatct gaatctgatt gagcaggcac     8700

ccctgaccgt ggccgagaag ctgcatcgct ggcgtaatag cgaagaggcc cgcaccgatc     8760

gcccttccca acagttgcgc agcctgaatg gcgaatggcg attccgttgc aatggctggc     8820

ggtaatattg ttctggatat taccagcaag gccgatagtt tgagttcttc tactcaggca     8880

agtgatgtta ttactaatca aagaagtatt gcgacaacgg ttaatttgcg tgatggacag     8940

actcttttac tcggtggcct cactgattat aaaaacactt ctcaggattc tggcgtaccg     9000

ttcctgtcta aaatcccttt aatcggcctc ctgtttagct cccgctctga ttctaacgag     9060

gaaagcacgt tatacgtgct cgtcaaagca accatagtac gcgccctgta gcggcgcatt     9120

aagcgcggcg ggtgtggtgg ttacgcgcag cgtgaccgct acacttgcca gcgccctagc     9180

gcccgctcct ttcgctttct tcccttcctt tctcgccacg ttcgccggcg aacgtggcga     9240

gaaaggaagg gaagaaagcg aaaggagcgg gcgctagggc gctggcaagt gtagcggtca     9300

cgctgcgcgt aaccaccaca cccgccgcgc ttaatgcgcc gctacagggc gcgtcccatt     9360

cgccattcag gctgcgcaac tgttgggaag ggcgatcggt gcgggcctct tcgctattac     9420

gccagctggc gaaaggggga tgtgctgcaa ggcgattaag ttgggtaacg ccagggtttt     9480

cccagtcacg acgttgtaaa acgacggcca gtgaattagg ttaattaagg cacacccgcc     9540

gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat tcaggctgcg caactgttgg     9600

gaagggcgat cggtgcgg                                                   9618


<210>  16
<211>  791
<212>  PRT
<213>  hBDDF8 sequence in FIG. 2

<400>  16

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Ala Thr Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Phe Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Leu Phe Val Glu Phe Thr Asp His Leu Phe Asn Ile 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Leu Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Arg Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu His Lys Phe Ile Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Arg Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Ile Thr Phe Leu Thr Ala Gln Thr Leu Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Ser Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Arg Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Ile Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Ile Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu 
        755                 760                 765             


Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
    770                 775                 780                 


Glu Glu Ile Asp Tyr Asp Asp 
785                 790     


<210>  17
<211>  791
<212>  PRT
<213>  hBDDF8 sequence with substitutions in FIG. 2

<400>  17

Met Gln Ile Glu Leu Ser Thr Cys Phe Phe Leu Cys Leu Leu Arg Phe 
1               5                   10                  15      


Cys Phe Ser Lys Val Arg Arg Tyr Tyr Leu Gly Ala Val Glu Leu Ser 
            20                  25                  30          


Trp Asp Tyr Met Gln Ser Asp Leu Gly Glu Leu Pro Val Asp Ala Arg 
        35                  40                  45              


Phe Pro Pro Arg Val Pro Lys Ser Leu Pro Phe Asn Thr Ser Val Val 
    50                  55                  60                  


Tyr Lys Lys Thr Val Phe Val Glu Phe Thr Asp His Leu Phe Asn Val 
65                  70                  75                  80  


Ala Lys Pro Arg Pro Pro Trp Met Gly Leu Leu Gly Pro Thr Ile Gln 
                85                  90                  95      


Ala Glu Val Tyr Asp Thr Val Val Ile Thr Leu Lys Asn Met Ala Ser 
            100                 105                 110         


His Pro Val Ser Leu His Ala Val Gly Val Ser Tyr Trp Lys Ala Ser 
        115                 120                 125             


Glu Gly Ala Glu Tyr Asp Asp Gln Thr Ser Gln Arg Glu Lys Glu Asp 
    130                 135                 140                 


Asp Lys Val Phe Pro Gly Gly Ser His Thr Tyr Val Trp Gln Val Leu 
145                 150                 155                 160 


Lys Glu Asn Gly Pro Met Ala Ser Asp Pro Leu Cys Leu Thr Tyr Ser 
                165                 170                 175     


Tyr Phe Ser His Val Asp Leu Val Lys Asp Leu Asn Ser Gly Leu Ile 
            180                 185                 190         


Gly Ala Leu Leu Val Cys Lys Glu Gly Ser Leu Ala Lys Glu Lys Thr 
        195                 200                 205             


Gln Thr Leu Gln Lys Phe Val Leu Leu Phe Ala Val Phe Asp Glu Gly 
    210                 215                 220                 


Lys Ser Trp His Ser Glu Thr Lys Asn Ser Leu Met Gln Asp Arg Asp 
225                 230                 235                 240 


Ala Ala Ser Ala Arg Ala Trp Pro Lys Met His Thr Val Asn Gly Tyr 
                245                 250                 255     


Val Asn Arg Ser Leu Pro Gly Leu Ile Gly Cys His Lys Lys Ser Val 
            260                 265                 270         


Tyr Trp His Val Ile Gly Met Gly Thr Thr Pro Glu Val His Ser Ile 
        275                 280                 285             


Phe Leu Glu Gly His Thr Phe Leu Val Arg Asn His Arg Gln Ala Ser 
    290                 295                 300                 


Leu Glu Ile Ser Pro Val Thr Phe Leu Thr Ala Gln Thr Phe Leu Met 
305                 310                 315                 320 


Asp Leu Gly Gln Phe Leu Leu Phe Cys His Ile Pro Ser His Gln His 
                325                 330                 335     


Asp Gly Met Glu Ala Tyr Val Lys Val Asp Ser Cys Pro Glu Glu Pro 
            340                 345                 350         


Gln Leu Arg Met Lys Asn Asn Glu Glu Ala Glu Asp Tyr Asp Asp Asp 
        355                 360                 365             


Leu Thr Asp Ser Glu Met Asp Val Val Ser Phe Asp Asp Asp Asn Ser 
    370                 375                 380                 


Pro Ser Phe Ile Gln Ile Arg Ser Val Ala Lys Lys His Pro Lys Thr 
385                 390                 395                 400 


Trp Val His Tyr Ile Ala Ala Glu Glu Glu Asp Trp Asp Tyr Ala Pro 
                405                 410                 415     


Leu Val Leu Ala Pro Asp Asp Arg Ser Tyr Lys Ser Gln Tyr Leu Asn 
            420                 425                 430         


Asn Gly Pro Gln Arg Ile Gly Arg Lys Tyr Lys Lys Val Arg Phe Met 
        435                 440                 445             


Ala Tyr Thr Asp Glu Thr Phe Lys Thr Arg Glu Ala Ile Gln His Glu 
    450                 455                 460                 


Ser Gly Ile Leu Gly Pro Leu Leu Tyr Gly Glu Val Gly Asp Thr Leu 
465                 470                 475                 480 


Leu Ile Ile Phe Lys Asn Gln Ala Ser Arg Pro Tyr Asn Ile Tyr Pro 
                485                 490                 495     


His Gly Ile Thr Asp Val Arg Pro Leu Tyr Ser Arg Arg Leu Pro Lys 
            500                 505                 510         


Gly Val Lys His Leu Lys Asp Phe Pro Ile Leu Pro Gly Glu Ile Phe 
        515                 520                 525             


Lys Tyr Lys Trp Thr Val Thr Val Glu Asp Gly Pro Thr Lys Ser Asp 
    530                 535                 540                 


Pro Arg Cys Leu Thr Arg Tyr Tyr Ser Ser Phe Val Asn Met Glu Arg 
545                 550                 555                 560 


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


Ser Val Asp Gln Arg Gly Asn Gln Ile Met Ser Asp Lys Arg Asn Val 
            580                 585                 590         


Ile Leu Phe Ser Val Phe Asp Glu Asn Arg Ser Trp Tyr Leu Thr Glu 
        595                 600                 605             


Asn Met Gln Arg Phe Leu Pro Asn Pro Ala Gly Val Gln Leu Glu Asp 
    610                 615                 620                 


Pro Glu Phe Gln Ala Ser Asn Ile Met His Ser Ile Asn Gly Tyr Val 
625                 630                 635                 640 


Phe Asp Ser Leu Gln Leu Ser Val Cys Leu His Glu Val Ala Tyr Trp 
                645                 650                 655     


Tyr Ile Leu Ser Val Gly Ala Gln Thr Asp Phe Leu Ser Val Phe Phe 
            660                 665                 670         


Ser Gly Tyr Thr Phe Lys His Lys Met Val Tyr Glu Asp Thr Leu Thr 
        675                 680                 685             


Leu Phe Pro Phe Ser Gly Glu Thr Val Phe Met Ser Met Glu Asn Pro 
    690                 695                 700                 


Gly Leu Trp Ile Leu Gly Cys His Asn Ser Asp Phe Arg Asn Arg Gly 
705                 710                 715                 720 


Met Thr Ala Leu Leu Lys Val Ser Ser Cys Asp Lys Asn Thr Gly Asp 
                725                 730                 735     


Tyr Tyr Glu Asp Ser Tyr Glu Asp Ile Ser Ala Tyr Leu Leu Ser Lys 
            740                 745                 750         


Asn Asn Ala Ile Glu Pro Arg Ser Phe Ser Gln Asn Pro Pro Val Leu 
        755                 760                 765             


Lys Arg His Gln Arg Glu Ile Thr Arg Thr Thr Leu Gln Ser Asp Gln 
    770                 775                 780                 


Glu Glu Ile Asp Tyr Asp Asp 
785                 790     


<210>  18
<211>  8106
<212>  DNA
<213>  pANG-TTR-hBDDF8

<400>  18
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct acgcgtgtct gtctgcacat ttcgtagagc gagtgttccg atactctaat      180

ctccctaggc aaggttcata tttgtgtagg ttacttattc tccttttgtt gactaagtca      240

ataatcagaa tcagcaggtt tggagtcagc ttggcaggga tcagcagcct gggttggaag      300

gagggggtat aaaagcccct tcaccaggag aagccgtcac acagatccac aagctcctgc      360

tagcaggtaa gtgccgtgtg tggttcccgc gggcctggcc tctttacggg ttatggccct      420

tgcgtgcctt gaattactga cactgacatc cactttttct ttttctccac aggtatcgat      480

gccaccatgc aaatagagct ctccacctgc ttctttctgt gccttttgcg attctgcttt      540

agtgccacca gaagatacta cctgggtgca gtggaactgt catgggacta tatgcaaagt      600

gatctcggtg agctgcctgt ggacgcaaga tttcctccta gagtgccaaa atcttttcca      660

ttcaacacct cagtcgtgta caaaaagact ctgtttgtag aattcacgga tcaccttttc      720

aacatcgcta agccaaggcc accctggatg ggtctgctag gtcctaccat ccaggctgag      780

gtttatgata cagtggtcat tacacttaag aacatggctt cccatcctgt cagtcttcat      840

gctgttggtg tatcctactg gaaagcttct gagggagctg aatatgatga tcagaccagt      900

caaagggaga aagaagatga taaagtcttc cctggtggaa gccatacata tgtctggcag      960

gtcctgaaag agaatggtcc aatggcctct gacccactgt gccttaccta ctcatatctt     1020

tctcatgtgg acctggtaaa agacttgaat tcaggcctca ttggagccct actagtatgt     1080

agagaaggga gtctggccaa ggaaaagaca cagaccttgc acaaatttat actacttttt     1140

gctgtatttg atgaagggaa aagttggcac tcagaaacaa agaactcctt gatgcaggat     1200

agggatgctg catctgctcg ggcctggcct aaaatgcaca cagtcaatgg ttatgtaaac     1260

aggtctctgc caggtctgat tggatgccac aggaaatcag tctattggca tgtgattgga     1320

atgggcacca ctcctgaagt gcactcaata ttcctcgaag gtcacacatt tcttgtgagg     1380

aaccatcgcc aggcgtcctt ggaaatctcg ccaataactt tccttactgc tcaaacactc     1440

ttgatggacc ttggacagtt tctactgttt tgtcatatct cttcccacca acatgatggc     1500

atggaagctt atgtcaaagt agacagctgt ccagaggaac cccaactacg aatgaaaaat     1560

aatgaagaag cggaagacta tgatgatgat cttactgatt ctgaaatgga tgtggtcagg     1620

tttgatgatg acaactctcc ttcctttatc caaattcgct cagttgccaa gaagcatcct     1680

aaaacttggg tacattacat tgctgctgaa gaggaggact gggactatgc tcccttagtc     1740

ctcgcccccg atgacagaag ttataaaagt caatatttga acaatggccc tcagcggatt     1800

ggtaggaagt acaaaaaagt ccgatttatg gcatacacag atgaaacctt taagactcgt     1860

gaagctattc agcatgaatc aggaatcttg ggacctttac tttatgggga agttggagac     1920

acactgttga ttatatttaa gaatcaagca agcagaccat ataacatcta ccctcacgga     1980

atcactgatg tccgtccttt gtattcaagg agattaccaa aaggtgtaaa acatttgaag     2040

gattttccaa ttctgccagg agaaatattc aaatataaat ggacagtgac tgtagaagat     2100

gggccaacta aatcagatcc tcggtgcctg acccgctatt actctagttt cgttaatatg     2160

gagagagatc tagcttcagg actcattggc cctctcctca tctgctacaa agaatctgta     2220

gatcaaagag gaaaccagat aatgtcagac aagaggaatg tcatcctgtt ttctgtattt     2280

gatgagaacc gaagctggta cctcacagag aatatacaac gctttctccc caatccagct     2340

ggagtgcagc ttgaggatcc agagttccaa gcctccaaca tcatgcacag catcaatggc     2400

tatgtttttg atagtttgca gttgtcagtt tgtttgcatg aggtggcata ctggtacatt     2460

ctaagcattg gagcacagac tgacttcctt tctgtcttct tctctggata taccttcaaa     2520

cacaaaatgg tctatgaaga cacactcacc ctattcccat tctcaggaga aactgtcttc     2580

atgtcgatgg aaaacccagg tctatggatt ctggggtgcc acaactcaga ctttcggaac     2640

agaggcatga ccgccttact gaaggtttct agttgtgaca agaacactgg tgattattac     2700

gaggacagtt atgaagatat ttcagcatac ttgctgagta aaaacaatgc cattgaacca     2760

agaagcttct cccagaatcc accagtcttg aaacgccatc aacgcgaaat aactcgtact     2820

actcttcagt cagatcaaga ggaaattgac tatgatgata ccatatcagt tgaaatgaag     2880

aaggaagatt ttgacattta tgatgaggat gaaaatcaga gcccccgcag ctttcaaaag     2940

aaaacacgac actattttat tgctgcagtg gagaggctct gggattatgg gatgagtagc     3000

tccccacatg ttctaagaaa cagggctcag agtggcagtg tccctcagtt caagaaagtt     3060

gttttccagg aatttactga tggctccttt actcagccct tataccgtgg agaactaaat     3120

gaacatttgg gactcctggg gccatatata agagcagaag ttgaagataa tatcatggta     3180

actttcagaa atcaggcctc tcgtccctat tccttctatt ctagccttat ttcttatgag     3240

gaagatcaga ggcaaggagc agaacctaga aaaaactttg tcaagcctaa tgaaaccaaa     3300

acttactttt ggaaagtgca acatcatatg gcacccacta aagatgagtt tgactgcaaa     3360

gcctgggctt atttctctga tgttgacctg gaaaaagatg tgcactcagg cctgattgga     3420

ccccttctgg tctgccacac taacacactg aaccctgctc atgggagaca agtgacagta     3480

caggaatttg ctctgttttt caccatcttt gatgagacca aaagctggta cttcactgaa     3540

aatatggaaa gaaactgcag ggctccctgc aatatccaga tggaagatcc cacttttaaa     3600

gagaattatc gcttccatgc aatcaatggc tacataatgg atacactacc tggcttagta     3660

atggctcagg atcaaaggat tcgatggtat ctgctcagca tgggcagcaa tgaaaacatc     3720

cattctattc atttcagtgg acatgtgttc actgtacgaa aaaaagagga gtataaaatg     3780

gcactgtaca atctctatcc aggtgttttt gagacagtgg aaatgttacc atccaaagct     3840

ggaatttggc gggtggaatg ccttattggc gagcatctac atgctgggat gagcacactt     3900

tttctggtgt acagcaataa gtgtcagact cccctgggaa tggcttctgg acacattaga     3960

gattttcaga ttacagcttc aggacaatat ggacagtggg ccccaaagct ggccagactt     4020

cattattccg gatcaatcaa tgcctggagc accaaggagc ccttttcttg gatcaaggtg     4080

gatctgttgg caccaatgat tattcacggc atcaagaccc agggtgcccg tcagaagttc     4140

tccagcctct acatctctca gtttatcatc atgtatagtc ttgatgggaa gaagtggcag     4200

acttatcgag gaaattccac tggaacctta atggtcttct ttggcaatgt ggattcatct     4260

gggataaaac acaatatttt taaccctcca attattgctc gatacatccg tttgcaccca     4320

actcattata gcattcgcag cactcttcgc atggagttga tgggctgtga tttaaatagt     4380

tgcagcatgc cattgggaat ggagagtaaa gcaatatcag atgcacagat tactgcttca     4440

tcctacttta ccaatatgtt tgccacctgg tctccttcaa aagctcgact tcacctccaa     4500

gggaggagta atgcctggag acctcaggtg aataatccaa aagagtggct gcaagtggac     4560

ttccagaaga caatgaaagt cacaggagta actactcagg gagtaaaatc tctgcttacc     4620

agcatgtatg tgaaggagtt cctcatctcc agcagtcaag atggccatca gtggactctc     4680

ttttttcaga atggcaaagt aaaggttttt cagggaaatc aagactcctt cacacctgtg     4740

gtgaactctc tagacccacc gttactgact cgctaccttc gaattcaccc ccagagttgg     4800

gtgcaccaga ttgccctgag gatggaggtt ctgggctgcg aggcacagga cctctactga     4860

ctcgagaata aaagatcaga gctctagaga tctgtgtgtt ggttttttgt gtgcggccgg     4920

gatctgagga acccctagtg atggagttgg ccactccctc tctgcgcgct cgctcgctca     4980

ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt tggtcgcccg gcctcagtga     5040

gcgagcgagc gcgcagagag ggagtggcca accccccccc ccccccccct gcaggcgatt     5100

ctcttgtttg ctccagactc tcaggcaatg acctgatagc ctttgtagag acctctcaaa     5160

aatagctacc ctctccggca tgaatttatc agctagaacg gttgaatatc atattgatgg     5220

tgatttgact gtctccggcc tttctcaccc gtttgaatct ttacctacac attactcagg     5280

cattgcattt aaaatatatg agggttctaa aaatttttat ccttgcgttg aaataaaggc     5340

ttctcccgca aaagtattac agggtcataa tgtttttggt acaaccgatt tagctttatg     5400

ctctgaggct ttattgctta attttgctaa ttctttgcct tgcctgtatg atttattgga     5460

tgttggaatt cctgatgcgg tattttctcc ttacgcatct gtgcggtatt tcacaccgca     5520

tatggtgcac tctcagtaca atctgctctg atgccgcata gttaagccag ccccgacacc     5580

cgccaacacc cgctgacgcg ccctgacggg cttgtctgct cccggcatcc gcttacagac     5640

aagctgtgac cgtctccggg agctgcatgt gtcagaggtt ttcaccgtca tcaccgaaac     5700

gcgcgagacg aaagggcctc gtgatacgcc tatttttata ggttaatgtc atgataataa     5760

tggtttctta gacgtcaggt ggcacttttc ggggaaatgt gcgcggaacc cctatttgtt     5820

tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc tgataaatgc     5880

ttcaataata ttgaaaaagg aagagtatga gtattcaaca tttccgtgtc gcccttattc     5940

ccttttttgc ggcattttgc cttcctgttt ttgctcaccc agaaacgctg gtgaaagtaa     6000

aagatgctga agatcagttg ggtgcacgag tgggttacat cgaactggat ctcaacagcg     6060

gtaagatcct tgagagtttt cgccccgaag aacgttttcc aatgatgagc acttttaaag     6120

ttctgctatg tggcgcggta ttatcccgta ttgacgccgg gcaagagcaa ctcggtcgcc     6180

gcatacacta ttctcagaat gacttggttg agtactcacc agtcacagaa aagcatctta     6240

cggatggcat gacagtaaga gaattatgca gtgctgccat aaccatgagt gataacactg     6300

cggccaactt acttctgaca acgatcggag gaccgaagga gctaaccgct tttttgcaca     6360

acatggggga tcatgtaact cgccttgatc gttgggaacc ggagctgaat gaagccatac     6420

caaacgacga gcgtgacacc acgatgcctg tagcaatggc aacaacgttg cgcaaactat     6480

taactggcga actacttact ctagcttccc ggcaacaatt aatagactgg atggaggcgg     6540

ataaagttgc aggaccactt ctgcgctcgg cccttccggc tggctggttt attgctgata     6600

aatctggagc cggtgagcgt gggtctcgcg gtatcattgc agcactgggg ccagatggta     6660

agccctcccg tatcgtagtt atctacacga cggggagtca ggcaactatg gatgaacgaa     6720

atagacagat cgctgagata ggtgcctcac tgattaagca ttggtaactg tcagaccaag     6780

tttactcata tatactttag attgatttaa aacttcattt ttaatttaaa aggatctagg     6840

tgaagatcct ttttgataat ctcatgacca aaatccctta acgtgagttt tcgttccact     6900

gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt tttctgcgcg     6960

taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt ttgccggatc     7020

aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag ataccaaata     7080

ctgttcttct agtgtagccg tagttaggcc accacttcaa gaactctgta gcaccgccta     7140

catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat aagtcgtgtc     7200

ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg ggctgaacgg     7260

ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg agatacctac     7320

agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac aggtatccgg     7380

taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga aacgcctggt     7440

atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt ttgtgatgct     7500

cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta cggttcctgg     7560

ccttttgctg gccttttgct cacatgttct ttcctgcgtt atcccctgat tctgtggata     7620

accgtattac cgcctttgag tgagctgata ccgctcgccg cagccgaacg accgagcgca     7680

gcgagtcagt gagcgaggaa gcggaagagc gcccaatacg caaaccgcct ctccccgcgc     7740

gttggccgat tcattaatgc agctgtggaa tgtgtgtcag ttagggtgtg gaaagtcccc     7800

aggctcccca gcaggcagaa gtatgcaaag catgcatctc aattagtcag caaccaggtg     7860

tggaaagtcc ccaggctccc cagcaggcag aagtatgcaa agcatgcatc tcaattagtc     7920

agcaaccata gtcccgcccc taactccgcc catcccgccc ctaactccgc ccagttccgc     7980

ccattctccg ccccatggct gactaatttt ttttatttat gcagaggccg aggccgcctc     8040

ggcctctgag ctattccaga agtagtgagg aggctttttt ggaggcctag gcttttgcaa     8100

aaagct                                                                8106


