                         SEQUENCE LISTING

<110>  University of Rochester
       Fay, Philip J.
       Wakabayashi, Hironao
 
<120>  RECOMBINANT FACTOR VIII HAVING INCREASED STABILITY

<130>  176/62591

<150>  60/984,518
<151>  2007-11-01

<150>  60/991,304
<151>  2007-11-30

<160>  2     

<170>  PatentIn version 3.5

<210>  1
<211>  6999
<212>  DNA
<213>  Homo sapiens

<400>  1
gccaccagaa gatactacct gggtgcagtg gaactgtcat gggactatat gcaaagtgat       60

ctcggtgagc tgcctgtgga cgcaagattt cctcctagag tgccaaaatc ttttccattc      120

aacacctcag tcgtgtacaa aaagactctg tttgtagaat tcacggatca ccttttcaac      180

atcgctaagc caaggccacc ctggatgggt ctgctaggtc ctaccatcca ggctgaggtt      240

tatgatacag tggtcattac acttaagaac atggcttccc atcctgtcag tcttcatgct      300

gttggtgtat cctactggaa agcttctgag ggagctgaat atgatgatca gaccagtcaa      360

agggagaaag aagatgataa agtcttccct ggtggaagcc atacatatgt ctggcaggtc      420

ctgaaagaga atggtccaat ggcctctgac ccactgtgcc ttacctactc atatctttct      480

catgtggacc tggtaaaaga cttgaattca ggcctcattg gagccctact agtatgtaga      540

gaagggagtc tggccaagga aaagacacag accttgcaca aatttatact actttttgct      600

gtatttgatg aagggaaaag ttggcactca gaaacaaaga actccttgat gcaggatagg      660

gatgctgcat ctgctcgggc ctggcctaaa atgcacacag tcaatggtta tgtaaacagg      720

tctctgccag gtctgattgg atgccacagg aaatcagtct attggcatgt gattggaatg      780

ggcaccactc ctgaagtgca ctcaatattc ctcgaaggtc acacatttct tgtgaggaac      840

catcgccagg cgtccttgga aatctcgcca ataactttcc ttactgctca aacactcttg      900

atggaccttg gacagtttct actgttttgt catatctctt cccaccaaca tgatggcatg      960

gaagcttatg tcaaagtaga cagctgtcca gaggaacccc aactacgaat gaaaaataat     1020

gaagaagcgg aagactatga tgatgatctt actgattctg aaatggatgt ggtcaggttt     1080

gatgatgaca actctccttc ctttatccaa attcgctcag ttgccaagaa gcatcctaaa     1140

acttgggtac attacattgc tgctgaagag gaggactggg actatgctcc cttagtcctc     1200

gcccccgatg acagaagtta taaaagtcaa tatttgaaca atggccctca gcggattggt     1260

aggaagtaca aaaaagtccg atttatggca tacacagatg aaacctttaa gactcgtgaa     1320

gctattcagc atgaatcagg aatcttggga cctttacttt atggggaagt tggagacaca     1380

ctgttgatta tatttaagaa tcaagcaagc agaccatata acatctaccc tcacggaatc     1440

actgatgtcc gtcctttgta ttcaaggaga ttaccaaaag gtgtaaaaca tttgaaggat     1500

tttccaattc tgccaggaga aatattcaaa tataaatgga cagtgactgt agaagatggg     1560

ccaactaaat cagatcctcg gtgcctgacc cgctattact ctagtttcgt taatatggag     1620

agagatctag cttcaggact cattggccct ctcctcatct gctacaaaga atctgtagat     1680

caaagaggaa accagataat gtcagacaag aggaatgtca tcctgttttc tgtatttgat     1740

gagaaccgaa gctggtacct cacagagaat atacaacgct ttctccccaa tccagctgga     1800

gtgcagcttg aggatccaga gttccaagcc tccaacatca tgcacagcat caatggctat     1860

gtttttgata gtttgcagtt gtcagtttgt ttgcatgagg tggcatactg gtacattcta     1920

agcattggag cacagactga cttcctttct gtcttcttct ctggatatac cttcaaacac     1980

aaaatggtct atgaagacac actcacccta ttcccattct caggagaaac tgtcttcatg     2040

tcgatggaaa acccaggtct atggattctg gggtgccaca actcagactt tcggaacaga     2100

ggcatgaccg ccttactgaa ggtttctagt tgtgacaaga acactggtga ttattacgag     2160

gacagttatg aagatatttc agcatacttg ctgagtaaaa acaatgccat tgaaccaaga     2220

agcttctccc agaattcaag acaccctagc actaggcaaa agcaatttaa tgccaccaca     2280

attccagaaa atgacataga gaagactgac ccttggtttg cacacagaac acctatgcct     2340

aaaatacaaa atgtctcctc tagtgatttg ttgatgctct tgcgacagag tcctactcca     2400

catgggctat ccttatctga tctccaagaa gccaaatatg agactttttc tgatgatcca     2460

tcacctggag caatagacag taataacagc ctgtctgaaa tgacacactt caggccacag     2520

ctccatcaca gtggggacat ggtatttacc cctgagtcag gcctccaatt aagattaaat     2580

gagaaactgg ggacaactgc agcaacagag ttgaagaaac ttgatttcaa agtttctagt     2640

acatcaaata atctgatttc aacaattcca tcagacaatt tggcagcagg tactgataat     2700

acaagttcct taggaccccc aagtatgcca gttcattatg atagtcaatt agataccact     2760

ctatttggca aaaagtcatc tccccttact gagtctggtg gacctctgag cttgagtgaa     2820

gaaaataatg attcaaagtt gttagaatca ggtttaatga atagccaaga aagttcatgg     2880

ggaaaaaatg tatcgtcaac agagagtggt aggttattta aagggaaaag agctcatgga     2940

cctgctttgt tgactaaaga taatgcctta ttcaaagtta gcatctcttt gttaaagaca     3000

aacaaaactt ccaataattc agcaactaat agaaagactc acattgatgg cccatcatta     3060

ttaattgaga atagtccatc agtctggcaa aatatattag aaagtgacac tgagtttaaa     3120

aaagtgacac ctttgattca tgacagaatg cttatggaca aaaatgctac agctttgagg     3180

ctaaatcata tgtcaaataa aactacttca tcaaaaaaca tggaaatggt ccaacagaaa     3240

aaagagggcc ccattccacc agatgcacaa aatccagata tgtcgttctt taagatgcta     3300

ttcttgccag aatcagcaag gtggatacaa aggactcatg gaaagaactc tctgaactct     3360

gggcaaggcc ccagtccaaa gcaattagta tccttaggac cagaaaaatc tgtggaaggt     3420

cagaatttct tgtctgagaa aaacaaagtg gtagtaggaa agggtgaatt tacaaaggac     3480

gtaggactca aagagatggt ttttccaagc agcagaaacc tatttcttac taacttggat     3540

aatttacatg aaaataatac acacaatcaa gaaaaaaaaa ttcaggaaga aatagaaaag     3600

aaggaaacat taatccaaga gaatgtagtt ttgcctcaga tacatacagt gactggcact     3660

aagaatttca tgaagaacct tttcttactg agcactaggc aaaatgtaga aggttcatat     3720

gacggggcat atgctccagt acttcaagat tttaggtcat taaatgattc aacaaataga     3780

acaaagaaac acacagctca tttctcaaaa aaaggggagg aagaaaactt ggaaggcttg     3840

ggaaatcaaa ccaagcaaat tgtagagaaa tatgcatgca ccacaaggat atctcctaat     3900

acaagccagc agaattttgt cacgcaacgt agtaagagag ctttgaaaca attcagactc     3960

ccactagaag aaacagaact tgaaaaaagg ataattgtgg atgacacctc aacccagtgg     4020

tccaaaaaca tgaaacattt gaccccgagc accctcacac agatagacta caatgagaag     4080

gagaaagggg ccattactca gtctccctta tcagattgcc ttacgaggag tcatagcatc     4140

cctcaagcaa atagatctcc attacccatt gcaaaggtat catcatttcc atctattaga     4200

cctatatatc tgaccagggt cctattccaa gacaactctt ctcatcttcc agcagcatct     4260

tatagaaaga aagattctgg ggtccaagaa agcagtcatt tcttacaagg agccaaaaaa     4320

aataaccttt ctttagccat tctaaccttg gagatgactg gtgatcaaag agaggttggc     4380

tccctgggga caagtgccac aaattcagtc acatacaaga aagttgagaa cactgttctc     4440

ccgaaaccag acttgcccaa aacatctggc aaagttgaat tgcttccaaa agttcacatt     4500

tatcagaagg acctattccc tacggaaact agcaatgggt ctcctggcca tctggatctc     4560

gtggaaggga gccttcttca gggaacagag ggagcgatta agtggaatga agcaaacaga     4620

cctggaaaag ttccctttct gagagtagca acagaaagct ctgcaaagac tccctccaag     4680

ctattggatc ctcttgcttg ggataaccac tatggtactc agataccaaa agaagagtgg     4740

aaatcccaag agaagtcacc agaaaaaaca gcttttaaga aaaaggatac cattttgtcc     4800

ctgaacgctt gtgaaagcaa tcatgcaata gcagcaataa atgagggaca aaataagccc     4860

gaaatagaag tcacctgggc aaagcaaggt aggactgaaa ggctgtgctc tcaaaaccca     4920

ccagtcttga aacgccatca acgggaaata actcgtacta ctcttcagtc agatcaagag     4980

gaaattgact atgatgatac catatcagtt gaaatgaaga aggaagattt tgacatttat     5040

gatgaggatg aaaatcagag cccccgcagc tttcaaaaga aaacacgaca ctattttatt     5100

gctgcagtgg agaggctctg ggattatggg atgagtagct ccccacatgt tctaagaaac     5160

agggctcaga gtggcagtgt ccctcagttc aagaaagttg ttttccagga atttactgat     5220

ggctccttta ctcagccctt ataccgtgga gaactaaatg aacatttggg actcctgggg     5280

ccatatataa gagcagaagt tgaagataat atcatggtaa ctttcagaaa tcaggcctct     5340

cgtccctatt ccttctattc tagccttatt tcttatgagg aagatcagag gcaaggagca     5400

gaacctagaa aaaactttgt caagcctaat gaaaccaaaa cttacttttg gaaagtgcaa     5460

catcatatgg cacccactaa agatgagttt gactgcaaag cctgggctta tttctctgat     5520

gttgacctgg aaaaagatgt gcactcaggc ctgattggac cccttctggt ctgccacact     5580

aacacactga accctgctca tgggagacaa gtgacagtac aggaatttgc tctgtttttc     5640

accatctttg atgagaccaa aagctggtac ttcactgaaa atatggaaag aaactgcagg     5700

gctccctgca atatccagat ggaagatccc acttttaaag agaattatcg cttccatgca     5760

atcaatggct acataatgga tacactacct ggcttagtaa tggctcagga tcaaaggatt     5820

cgatggtatc tgctcagcat gggcagcaat gaaaacatcc attctattca tttcagtgga     5880

catgtgttca ctgtacgaaa aaaagaggag tataaaatgg cactgtacaa tctctatcca     5940

ggtgtttttg agacagtgga aatgttacca tccaaagctg gaatttggcg ggtggaatgc     6000

cttattggcg agcatctaca tgctgggatg agcacacttt ttctggtgta cagcaataag     6060

tgtcagactc ccctgggaat ggcttctgga cacattagag attttcagat tacagcttca     6120

ggacaatatg gacagtgggc cccaaagctg gccagacttc attattccgg atcaatcaat     6180

gcctggagca ccaaggagcc cttttcttgg atcaaggtgg atctgttggc accaatgatt     6240

attcacggca tcaagaccca gggtgcccgt cagaagttct ccagcctcta catctctcag     6300

tttatcatca tgtatagtct tgatgggaag aagtggcaga cttatcgagg aaattccact     6360

ggaaccttaa tggtcttctt tggcaatgtg gattcatctg ggataaaaca caatattttt     6420

aaccctccaa ttattgctcg atacatccgt ttgcacccaa ctcattatag cattcgcagc     6480

actcttcgca tggagttgat gggctgtgat ttaaatagtt gcagcatgcc attgggaatg     6540

gagagtaaag caatatcaga tgcacagatt actgcttcat cctactttac caatatgttt     6600

gccacctggt ctccttcaaa agctcgactt cacctccaag ggaggagtaa tgcctggaga     6660

cctcaggtga ataatccaaa agagtggctg caagtggact tccagaagac aatgaaagtc     6720

acaggagtaa ctactcaggg agtaaaatct ctgcttacca gcatgtatgt gaaggagttc     6780

ctcatctcca gcagtcaaga tggccatcag tggactctct tttttcagaa tggcaaagta     6840

aaggtttttc agggaaatca agactccttc acacctgtgg tgaactctct agacccaccg     6900

ttactgactc gctaccttcg aattcacccc cagagttggg tgcaccagat tgccctgagg     6960

atggaggttc tgggctgcga ggcacaggac ctctactga                            6999


<210>  2
<211>  2332
<212>  PRT
<213>  Homo sapiens

<400>  2

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 Val 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  Glu 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         


