                         SEQUENCE LISTING

<110>  The United States of America, as represented by the 
       Secretary, Department of Health and Human Services
       Baron, Jeffrey
       Cheung, Crystal
       Lui, Julian
       Dimitrov, Dimiter
       Zhu, Zhongyu
 
<120>  CARTILAGE TARGETING AGENTS AND THEIR USE

<130>  4239-92095-02

<150>  US 61/927,904
<151>  2014-01-15

<160>  53    

<170>  PatentIn version 3.5

<210>  1
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody heavy chain variable region

<400>  1

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Gln Gly Tyr Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  2
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody light chain variable region

<400>  2

Asp Val Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 
            20                  25                  30          


Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Leu 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg 
            100                 105             


<210>  3
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody heavy chain variable region

<400>  3

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


Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn 
            20                  25                  30          


Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 
        35                  40                  45              


Trp Leu Gly Arg Thr Tyr Tyr Gly Ser Lys Trp Tyr Asn Asp Tyr Ala 
    50                  55                  60                  


Pro Ser Val Lys Ser Arg Ile Ser Ile Asn Pro Asp Thr Ser Lys Asn 
65                  70                  75                  80  


Gln Phe Ser Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val 
                85                  90                  95      


Tyr Tyr Cys Thr Arg Gly Ile Trp Asn Ala Phe Asp Ile Trp Gly Gln 
            100                 105                 110         


Gly Thr Met Val Thr Val Ser Ser 
        115                 120 


<210>  4
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody light chain variable region

<400>  4

Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln 
1               5                   10                  15      


Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala 
            20                  25                  30          


Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Leu Leu Val Ile Tyr 
        35                  40                  45              


Asp Arg Asp Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser 
    50                  55                  60                  


Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Thr Ser Leu Ser Trp 
                85                  90                  95      


Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly 
            100                 105             


<210>  5
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody heavy chain variable region

<400>  5

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


Gly Arg Ile Ile Pro Ile Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Trp Gly Ser Gly Ser His Ala Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Thr Val Thr Val Ser Ser 
        115                 


<210>  6
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  antibody light chain variable region

<400>  6

Ser Tyr Glu Leu Thr Gln Pro Pro Ser Thr Ser Gly Thr Pro Gly Gln 
1               5                   10                  15      


Arg Val Ala Ile Ser Cys Ser Gly Ala Ser Ser Asn Ile Gly Ser Asn 
            20                  25                  30          


Ala Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 
        35                  40                  45              


Ile Tyr Ser Asn Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 
    50                  55                  60                  


Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 
65                  70                  75                  80  


Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu 
                85                  90                  95      


Asn Gly Trp Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly 
            100                 105                 110     


<210>  7
<211>  708
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scFv sequence

<400>  7
ctggtgcagt ctggggctga ggtgaagaag cctggggcct cagtgaaggt ctcctgcaag       60

gcttctggag gcaccttcag cagctatgct atcagctggg tgcgacaggc ccctggacaa      120

gggcttgagt ggatgggagg gatcatccct atctttggta cagcaaacta cgcacagaag      180

ttccagggca gagtcacgat taccgcggac aaatccacga gcacagccta catggagctg      240

agcagcctga gatctgagga cacggccgtg tattactgtg cgagaggcca agggtattgg      300

ttcgacccct ggggccaggg aaccctggtc accgtctcct caggaggtgg cgggtctggt      360

ggaggcgcta gcagtggtgg cggatccgac gtccagttga cccagtctcc atcctccctg      420

tctgcatctg taggagacag agtcaccatc acttgccagg cgagtcagga cattagcaac      480

tatttaaatt ggtatcagca gaaaccaggg aaagccccta agctcctgat ctacgatgca      540

tccaatttgg aaacaggggt cccatcaagg ttcagtggaa gtggatctgg gacagatttt      600

actttcacca tcagcagcct gcagcctgaa gatattgcaa catattactg tcaacagtat      660

gataatctcc cgctcacttt cggcggaggg accaagctgg agatcaaa                   708


<210>  8
<211>  726
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scFv sequence

<400>  8
caggtacagc tgcagcagtc aggtccagga ctggtgaagc cctcgcagac cctctcactc       60

acctgtgcca tctccgggga cagtgtctct agcaacagtg ctgcttggaa ctggatcagg      120

cagtccccat cgagaggcct tgagtggctg ggaaggacat actacgggtc caagtggtat      180

aatgattatg cgccatctgt gaaaagtcga ataagtatca acccagacac atccaagaac      240

cagttctccc tgcaactgaa ctctgtgact cccgaagaca cggctgtgta ttactgtaca      300

aggggtattt ggaatgcttt tgatatctgg ggccaaggga caatggtcac cgtctcttca      360

ggaggtggcg ggtctggtgg aggcgctagc ggtggtggcg gatcctcttc tgagctgact      420

caggaccctg ctgtgtctgt ggccttggga cagacagtca ggatcacatg ccaaggagac      480

agcctcagaa gctattatgc aagctggtac cagcagaagc caggacaggc ccctttactt      540

gtcatctatg atagggacaa ccggccctca gggatcccag accgattctc tggctccagc      600

tcaggaaaca cagcttcctt gaccatcact ggggctcagg cggaagatga ggctgattat      660

tactgccagt cctatgacac cagcctgagt tgggtgttcg gcggaggcac ccagctgacc      720

gtcctc                                                                 726


<210>  9
<211>  732
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scFv sequence

<400>  9
gaggtccagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc       60

tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc      120

cctggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat agcaaactac      180

gcacagaagt tccagggcag agtcacgatt accgcggaca aatccacgag cacagcctac      240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagatggggt      300

agtgggagcc atgcttttga tatctggggc caagggacca cggtcaccgt ctcctcagga      360

ggtggcgggt ctggtggagg cgctagcagt ggtggcggat cctcctatga gctgactcag      420

ccaccctcga cgtctgggac ccccgggcag agggtcgcca tctcttgttc tggggccagt      480

tccaatatcg gaagtaatgc tgttagctgg taccagcagc tcccaggaac ggcccccaaa      540

ctcctcatct atagcaataa tcaacggccc tcaggggtcc ctgaccgatt ctctggctcc      600

aagtctggca cctcagcctc cctggccatc agtgggctcc ggtccgagga tgaggctgat      660

tattactgtg cagcatggga tgacagcctc aatggctggg tgttcggcgg agggacccag      720

ctcaccgttt ta                                                          732


<210>  10
<211>  236
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv sequence

<400>  10

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


Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser 
            20                  25                  30          


Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile 
        35                  40                  45              


Ile Pro Ile Phe Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg 
    50                  55                  60                  


Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu Leu 
65                  70                  75                  80  


Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly 
                85                  90                  95      


Gln Gly Tyr Trp Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr Val 
            100                 105                 110         


Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Ser Gly Gly Gly 
        115                 120                 125             


Ser Asp Val Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val 
    130                 135                 140                 


Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn 
145                 150                 155                 160 


Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 
                165                 170                 175     


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


Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln 
        195                 200                 205             


Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro 
    210                 215                 220                 


Leu Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
225                 230                 235     


<210>  11
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv sequence

<400>  11

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


Leu Thr Cys Ala Ile Ser Gly Asp Ser Val Ser Ser Asn Ser Ala Ala 
            20                  25                  30          


Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu Trp Leu Gly 
        35                  40                  45              


Arg Thr Tyr Tyr Gly Ser Lys Trp Tyr Asn Asp Tyr Ala Pro Ser Val 
    50                  55                  60                  


Lys Ser Arg Ile Ser Ile Asn Pro Asp Thr Ser Lys Asn Gln Phe Ser 
65                  70                  75                  80  


Leu Gln Leu Asn Ser Val Thr Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Thr Arg Gly Ile Trp Asn Ala Phe Asp Ile Trp Gly Gln Gly Thr Met 
            100                 105                 110         


Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Ser Ser Glu Leu Thr Gln Asp Pro Ala Val Ser Val 
    130                 135                 140                 


Ala Leu Gly Gln Thr Val Arg Ile Thr Cys Gln Gly Asp Ser Leu Arg 
145                 150                 155                 160 


Ser Tyr Tyr Ala Ser Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Leu 
                165                 170                 175     


Leu Val Ile Tyr Asp Arg Asp Asn Arg Pro Ser Gly Ile Pro Asp Arg 
            180                 185                 190         


Phe Ser Gly Ser Ser Ser Gly Asn Thr Ala Ser Leu Thr Ile Thr Gly 
        195                 200                 205             


Ala Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Thr 
    210                 215                 220                 


Ser Leu Ser Trp Val Phe Gly Gly Gly Thr Gln Leu Thr Val Leu 
225                 230                 235                 


<210>  12
<211>  241
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv sequence

<400>  12

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


Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser 
            20                  25                  30          


Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Arg Ile 
        35                  40                  45              


Ile Pro Ile Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg 
    50                  55                  60                  


Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu Leu 
65                  70                  75                  80  


Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Trp 
                85                  90                  95      


Gly Ser Gly Ser His Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         


Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ala Ser Ser Gly 
        115                 120                 125             


Gly Gly Ser Ser Tyr Glu Leu Thr Gln Pro Pro Ser Thr Ser Gly Thr 
    130                 135                 140                 


Pro Gly Gln Arg Val Ala Ile Ser Cys Ser Gly Ala Ser Ser Asn Ile 
145                 150                 155                 160 


Gly Ser Asn Ala Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro 
                165                 170                 175     


Lys Leu Leu Ile Tyr Ser Asn Asn Gln Arg Pro Ser Gly Val Pro Asp 
            180                 185                 190         


Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser 
        195                 200                 205             


Gly Leu Arg Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp 
    210                 215                 220                 


Asp Ser Leu Asn Gly Trp Val Phe Gly Gly Gly Thr Gln Leu Thr Val 
225                 230                 235                 240 


Leu 
    


<210>  13
<211>  1465
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scFv-Fc sequence

<400>  13
ctggtgcagt ctggggctga ggtgaagaag cctggggcct cagtgaaggt ctcctgcaag       60

gcttctggag gcaccttcag cagctatgct atcagctggg tgcgacaggc ccctggacaa      120

gggcttgagt ggatgggagg gatcatccct atctttggta cagcaaacta cgcacagaag      180

ttccagggca gagtcacgat taccgcggac aaatccacga gcacagccta catggagctg      240

agcagcctga gatctgagga cacggccgtg tattactgtg cgagaggcca agggtattgg      300

ttcgacccct ggggccaggg aaccctggtc accgtctcct caggaggtgg cgggtctggt      360

ggaggcgcta gcagtggtgg cggatccgac gtccagttga cccagtctcc atcctccctg      420

tctgcatctg taggagacag agtcaccatc acttgccagg cgagtcagga cattagcaac      480

tatttaaatt ggtatcagca gaaaccaggg aaagccccta agctcctgat ctacgatgca      540

tccaatttgg aaacaggggt cccatcaagg ttcagtggaa gtggatctgg gacagatttt      600

actttcacca tcagcagcct gcagcctgaa gatattgcaa catattactg tcaacagtat      660

gataatctcc cgctcacttt cggcggaggg accaagctgg agatcaaacg tggccaggcc      720

ggccaagggc ccgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg      780

ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc      840

cctgaggtca catgcgtggt ggtggacgtg agccacgaag accctgaggt caagttcaac      900

tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac      960

aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc     1020

aaggagtaca agtgcaaggt ctccaacaaa gccctcccag cccccatcga gaaaaccatc     1080

tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggat     1140

gagctgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac     1200

atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc     1260

gtgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg     1320

tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac     1380

acgcagaaga gcctctccct gtctcggggt aaagcggccg ctcgaggact aaacgacatc     1440

ttcgaggctc agaaaatcga atgca                                           1465


<210>  14
<211>  1482
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scFv-Fc sequence

<400>  14
caggtacagc tgcagcagtc aggtccagga ctggtgaagc cctcgcagac cctctcactc       60

acctgtgcca tctccgggga cagtgtctct agcaacagtg ctgcttggaa ctggatcagg      120

cagtccccat cgagaggcct tgagtggctg ggaaggacat actacgggtc caagtggtat      180

aatgattatg cgccatctgt gaaaagtcga ataagtatca acccagacac atccaagaac      240

cagttctccc tgcaactgaa ctctgtgact cccgaagaca cggctgtgta ttactgtaca      300

aggggtattt ggaatgcttt tgatatctgg ggccaaggga caatggtcac cgtctcttca      360

ggaggtggcg ggtctggtgg aggcgctagc ggtggtggcg gatcctcttc tgagctgact      420

caggaccctg ctgtgtctgt ggccttggga cagacagtca ggatcacatg ccaaggagac      480

agcctcagaa gctattatgc aagctggtac cagcagaagc caggacaggc ccctttactt      540

gtcatctatg atagggacaa ccggccctca gggatcccag accgattctc tggctccagc      600

tcaggaaaca cagcttcctt gaccatcact ggggctcagg cggaagatga ggctgattat      660

tactgccagt cctatgacac cagcctgagt tgggtgttcg gcggaggcac ccagctgacc      720

gtcctcggtg gccaggccgg ccaagggccc gacaaaactc acacatgccc accgtgccca      780

gcacctgaac tcctgggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc      840

ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac      900

cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag      960

ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac     1020

caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc     1080

cccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc     1140

ctgcccccat cccgggatga gctgaccaag aaccaggtca gcctgactgc ctggtcaaag     1200

gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg gagaacaact     1260

acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac agcaagctca     1320

ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg atgcatgagg     1380

ctctgcacaa ccactacacg cagaagagcc tctccctgtc tccgggtaaa gcggccgctc     1440

gaggactaaa cgacatcttc gaggctcaga aaatcgaagg ca                        1482


<210>  15
<211>  1489
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  scFv-Fc sequence

<400>  15
gaggtccagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc       60

tcctgcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc      120

cctggacaag ggcttgagtg gatgggaagg atcatcccta tccttggtat agcaaactac      180

gcacagaagt tccagggcag agtcacgatt accgcggaca aatccacgag cacagcctac      240

atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagatggggt      300

agtgggagcc atgcttttga tatctggggc caagggacca cggtcaccgt ctcctcagga      360

ggtggcgggt ctggtggagg cgctagcagt ggtggcggat cctcctatga gctgactcag      420

ccaccctcga cgtctgggac ccccgggcag agggtcgcca tctcttgttc tggggccagt      480

tccaatatcg gaagtaatgc tgttagctgg taccagcagc tcccaggaac ggcccccaaa      540

ctcctcatct atagcaataa tcaacggccc tcaggggtcc ctgaccgatt ctctggctcc      600

aagtctggca cctcagcctc cctggccatc agtgggctcc ggtccgagga tgaggctgat      660

tattactgtg cagcatggga tgacagcctc aatggctggg tgttcggcgg agggacccag      720

ctcaccgttt taggtggcca ggccggccaa gggcccgaca aaactcacac atgcccaccg      780

tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccc caaacccaag      840

gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac      900

gaagaccctg aggtcaagtt caactggtac gtggacggcg tggaggtgca taatgccaag      960

acaaagccgc gggaggagca gtacaacagc acgtaccgtg tggtcagcgt cctcaccgtc     1020

ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaagccctc     1080

ccagccccca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg     1140

tacaccctgc ccccatcccg ggatgagctg accaagaacc aggtcagcct gacctgcctg     1200

gtcaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag     1260

aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc     1320

aagctcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg     1380

catgaggctc tgcacaacca ctacacgcag aagagcctct ccctgtctcc gggtaaagcg     1440

gccgctcgag gactaaacga catcttcgag gctcagaaaa tcgaaggca                 1489


<210>  16
<211>  486
<212>  PRT
<213>  homo sapiens

<400>  16

Met Pro Arg Pro Ala Pro Ala Arg Arg Leu Pro Gly Leu Leu Leu Leu 
1               5                   10                  15      


Leu Trp Pro Leu Leu Leu Leu Pro Ser Ala Ala Pro Asp Pro Val Ala 
            20                  25                  30          


Arg Pro Gly Phe Arg Arg Leu Glu Thr Arg Gly Pro Gly Gly Ser Pro 
        35                  40                  45              


Gly Arg Arg Pro Ser Pro Ala Ala Pro Asp Gly Ala Pro Ala Ser Gly 
    50                  55                  60                  


Thr Ser Glu Pro Gly Arg Ala Arg Gly Ala Gly Val Cys Lys Ser Arg 
65                  70                  75                  80  


Pro Leu Asp Leu Val Phe Ile Ile Asp Ser Ser Arg Ser Val Arg Pro 
                85                  90                  95      


Leu Glu Phe Thr Lys Val Lys Thr Phe Val Ser Arg Ile Ile Asp Thr 
            100                 105                 110         


Leu Asp Ile Gly Pro Ala Asp Thr Arg Val Ala Val Val Asn Tyr Ala 
        115                 120                 125             


Ser Thr Val Lys Ile Glu Phe Gln Leu Gln Ala Tyr Thr Asp Lys Gln 
    130                 135                 140                 


Ser Leu Lys Gln Ala Val Gly Arg Ile Thr Pro Leu Ser Thr Gly Thr 
145                 150                 155                 160 


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


Glu Ala Gly Ala Arg Glu Pro Ser Ser Asn Ile Pro Lys Val Ala Ile 
            180                 185                 190         


Ile Val Thr Asp Gly Arg Pro Gln Asp Gln Val Asn Glu Val Ala Ala 
        195                 200                 205             


Arg Ala Gln Ala Ser Gly Ile Glu Leu Tyr Ala Val Gly Val Asp Arg 
    210                 215                 220                 


Ala Asp Met Ala Ser Leu Lys Met Met Ala Ser Glu Pro Leu Glu Glu 
225                 230                 235                 240 


His Val Phe Tyr Val Glu Thr Tyr Gly Val Ile Glu Lys Leu Ser Ser 
                245                 250                 255     


Arg Phe Gln Glu Thr Phe Cys Ala Leu Asp Pro Cys Val Leu Gly Thr 
            260                 265                 270         


His Gln Cys Gln His Val Cys Ile Ser Asp Gly Glu Gly Lys His His 
        275                 280                 285             


Cys Glu Cys Ser Gln Gly Tyr Thr Leu Asn Ala Asp Lys Lys Thr Cys 
    290                 295                 300                 


Ser Ala Leu Asp Arg Cys Ala Leu Asn Thr His Gly Cys Glu His Ile 
305                 310                 315                 320 


Cys Val Asn Asp Arg Ser Gly Ser Tyr His Cys Glu Cys Tyr Glu Gly 
                325                 330                 335     


Tyr Thr Leu Asn Glu Asp Arg Lys Thr Cys Ser Ala Gln Asp Lys Cys 
            340                 345                 350         


Ala Leu Gly Thr His Gly Cys Gln His Ile Cys Val Asn Asp Arg Thr 
        355                 360                 365             


Gly Ser His His Cys Glu Cys Tyr Glu Gly Tyr Thr Leu Asn Ala Asp 
    370                 375                 380                 


Lys Lys Thr Cys Ser Val Arg Asp Lys Cys Ala Leu Gly Ser His Gly 
385                 390                 395                 400 


Cys Gln His Ile Cys Val Ser Asp Gly Ala Ala Ser Tyr His Cys Asp 
                405                 410                 415     


Cys Tyr Pro Gly Tyr Thr Leu Asn Glu Asp Lys Lys Thr Cys Ser Ala 
            420                 425                 430         


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


Glu Ala Thr Leu Ala Phe Gln Asp Lys Val Ser Ser Tyr Leu Gln Arg 
    450                 455                 460                 


Leu Asn Thr Lys Leu Asp Asp Ile Leu Glu Lys Leu Lys Ile Asn Glu 
465                 470                 475                 480 


Tyr Gly Gln Ile His Arg 
                485     


<210>  17
<211>  2600
<212>  DNA
<213>  homo sapiens

<400>  17
aaatccgagc ctcgcgtggg ctcctggccc ccgacggaca ccaccaggcc cacggagccc       60

accatgccgc gcccggcccc cgcgcgccgc ctcccgggac tcctcctgct gctctggccg      120

ctgctgctgc tgccctccgc cgcccccgac cccgtggccc gcccgggctt ccggaggctg      180

gagacccgag gtcccggggg cagccctgga cgccgcccct ctcctgcggc tcccgacggc      240

gcgcccgctt ccgggaccag cgagcctggc cgcgcccgcg gtgcaggtgt ttgcaagagc      300

agacccttgg acctggtgtt tatcattgat agttctcgta gcgtacggcc cctggaattc      360

accaaagtga aaacttttgt ctcccggata atcgacactc tggacattgg gccagccgac      420

acgcgggtgg cagtggtgaa ctatgctagc actgtgaaga tcgagttcca actccaggcc      480

tacacagata agcagtccct gaagcaggcc gtgggtcgaa tcacaccctt gtcaacaggc      540

accatgtcag gcctagccat ccagacagca atggacgaag ccttcacagt ggaggcaggg      600

gctcgagagc cctcttctaa catccctaag gtggccatca ttgttacaga tgggaggccc      660

caggaccagg tgaatgaggt ggcggctcgg gcccaagcat ctggtattga gctctatgct      720

gtgggcgtgg accgggcaga catggcgtcc ctcaagatga tggccagtga gcccctagag      780

gagcatgttt tctacgtgga gacctatggg gtcattgaga aactttcctc tagattccag      840

gaaaccttct gtgcgctgga cccctgtgtg cttggaacac accagtgcca gcacgtctgc      900

atcagtgatg gggaaggcaa gcaccactgt gagtgtagcc aaggatacac cttgaatgcc      960

gacaagaaaa cgtgttcagc tcttgatagg tgtgctctta acacccacgg atgtgagcac     1020

atctgtgtga atgacagaag tggctcttat cattgtgagt gctatgaagg ttataccttg     1080

aatgaagaca ggaaaacttg ttcagctcaa gataaatgtg ctttgggtac ccatgggtgt     1140

cagcacattt gtgtgaatga cagaacaggg tcccatcatt gtgaatgcta tgagggctac     1200

actctgaatg cagataaaaa aacatgttca gtccgtgaca agtgtgccct aggctctcat     1260

ggttgccagc acatttgtgt gagtgatggg gccgcatcct accactgtga ttgctatcct     1320

ggctacacct taaatgagga caagaaaaca tgttcagcca ctgaggaagc acgaagactt     1380

gtttccactg aagatgcttg tggatgtgaa gctacactgg cattccagga caaggtcagc     1440

tcgtatcttc aaagactgaa cactaaactt gatgacattt tggagaagtt gaaaataaat     1500

gaatatggac aaatacatcg ttaaattgct ccaatttctc acctgaaaat gtggacagct     1560

tggtgtactt aatactcatg cattcttttg cacacctgtt attgccaatg ttcctgctaa     1620

taatttgcca ttatctgtat taatgcttga atattactgg ataaattgta tgaagatctt     1680

ctgcagaatc agcatgattc ttccaaggaa atacatatgc agatacttat taagagcaaa     1740

ctttagtgtc tctaagttat gactgtgaaa tgattggtag gaaatagaat gaaaagttta     1800

gtgtttcttt atctactaat tgagccattt aatttttaaa tgtttatatt agataaccat     1860

attcacaatg gaaactttag gtctagtttc ttttgatagt atttataata taaatcaatc     1920

ttattactga gagtgcaaat tgtacaaggt atttacacat acaacttcat ataactgaga     1980

tgaatgtaat tttgaactgt ttaacacttt ttgttttttg cttattttgt tggagtatta     2040

ttgaagatgt gatcaataga ttgtaataca catatctaaa aatagttaac acagatcaag     2100

tgaacattac attgccattt ttaattcatt ctggtctttg aaagaaatgt actactaaag     2160

agcactagtt gtgaatttag ggtgttaaac tttttaccaa gtacaaaaat cccaaattca     2220

ctttattatt ttgcttcagg atccaagtga caaagttata tatttataaa attgctataa     2280

atcgacaaaa tctaatgttg tctttttaat gttagtgatc cacctgcctc agcctcccaa     2340

agtgctggga ttacaggctt gaaagtctaa ctttttttta cttatatatt tgatacatat     2400

aattcttttg gctttgaaac ttgcaacttt gagaacaaaa cagtccttta aattttgcac     2460

tgctcaattc tgtttttcgt ttgcattgtc tttaatataa taaaagttat tacctttaca     2520

tattatcatg tctatttttg atgactcatc aattttgtct attaaagata tttctttaaa     2580

ttaaaaaaaa aaaaaaaaaa                                                 2600


<210>  18
<211>  217
<212>  PRT
<213>  homo sapiens

<400>  18

Met Ala Thr Gly Ser Arg Thr Ser Leu Leu Leu Ala Phe Gly Leu Leu 
1               5                   10                  15      


Cys Leu Pro Trp Leu Gln Glu Gly Ser Ala Phe Pro Thr Ile Pro Leu 
            20                  25                  30          


Ser Arg Leu Phe Asp Asn Ala Met Leu Arg Ala His Arg Leu His Gln 
        35                  40                  45              


Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu Glu Ala Tyr Ile Pro Lys 
    50                  55                  60                  


Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro Gln Thr Ser Leu Cys Phe 
65                  70                  75                  80  


Ser Glu Ser Ile Pro Thr Pro Ser Asn Arg Glu Glu Thr Gln Gln Lys 
                85                  90                  95      


Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu Leu Leu Ile Gln Ser Trp 
            100                 105                 110         


Leu Glu Pro Val Gln Phe Leu Arg Ser Val Phe Ala Asn Ser Leu Val 
        115                 120                 125             


Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp Leu Leu Lys Asp Leu Glu 
    130                 135                 140                 


Glu Gly Ile Gln Thr Leu Met Gly Arg Leu Glu Asp Gly Ser Pro Arg 
145                 150                 155                 160 


Thr Gly Gln Ile Phe Lys Gln Thr Tyr Ser Lys Phe Asp Thr Asn Ser 
                165                 170                 175     


His Asn Asp Asp Ala Leu Leu Lys Asn Tyr Gly Leu Leu Tyr Cys Phe 
            180                 185                 190         


Arg Lys Asp Met Asp Lys Val Glu Thr Phe Leu Arg Ile Val Gln Cys 
        195                 200                 205             


Arg Ser Val Glu Gly Ser Cys Gly Phe 
    210                 215         


<210>  19
<211>  191
<212>  PRT
<213>  homo sapiens

<400>  19

Phe Pro Thr Ile Pro Leu Ser Arg Leu Phe Asp Asn Ala Met Leu Arg 
1               5                   10                  15      


Ala His Arg Leu His Gln Leu Ala Phe Asp Thr Tyr Gln Glu Phe Glu 
            20                  25                  30          


Glu Ala Tyr Ile Pro Lys Glu Gln Lys Tyr Ser Phe Leu Gln Asn Pro 
        35                  40                  45              


Gln Thr Ser Leu Cys Phe Ser Glu Ser Ile Pro Thr Pro Ser Asn Arg 
    50                  55                  60                  


Glu Glu Thr Gln Gln Lys Ser Asn Leu Glu Leu Leu Arg Ile Ser Leu 
65                  70                  75                  80  


Leu Leu Ile Gln Ser Trp Leu Glu Pro Val Gln Phe Leu Arg Ser Val 
                85                  90                  95      


Phe Ala Asn Ser Leu Val Tyr Gly Ala Ser Asp Ser Asn Val Tyr Asp 
            100                 105                 110         


Leu Leu Lys Asp Leu Glu Glu Gly Ile Gln Thr Leu Met Gly Arg Leu 
        115                 120                 125             


Glu Asp Gly Ser Pro Arg Thr Gly Gln Ile Phe Lys Gln Thr Tyr Ser 
    130                 135                 140                 


Lys Phe Asp Thr Asn Ser His Asn Asp Asp Ala Leu Leu Lys Asn Tyr 
145                 150                 155                 160 


Gly Leu Leu Tyr Cys Phe Arg Lys Asp Met Asp Lys Val Glu Thr Phe 
                165                 170                 175     


Leu Arg Ile Val Gln Cys Arg Ser Val Glu Gly Ser Cys Gly Phe 
            180                 185                 190     


<210>  20
<211>  822
<212>  DNA
<213>  homo sapiens

<400>  20
aggatcccaa ggcccaactc cccgaaccac tcagggtcct gtggacagct cacctagctg       60

caatggctac aggctcccgg acgtccctgc tcctggcttt tggcctgctc tgcctgccct      120

ggcttcaaga gggcagtgcc ttcccaacca ttcccttatc caggcttttt gacaacgcta      180

tgctccgcgc ccatcgtctg caccagctgg cctttgacac ctaccaggag tttgaagaag      240

cctatatccc aaaggaacag aagtattcat tcctgcagaa cccccagacc tccctctgtt      300

tctcagagtc tattccgaca ccctccaaca gggaggaaac acaacagaaa tccaacctag      360

agctgctccg catctccctg ctgctcatcc agtcgtggct ggagcccgtg cagttcctca      420

ggagtgtctt cgccaacagc ctggtgtacg gcgcctctga cagcaacgtc tatgacctcc      480

taaaggacct agaggaaggc atccaaacgc tgatggggag gctggaagat ggcagccccc      540

ggactgggca gatcttcaag cagacctaca gcaagttcga cacaaactca cacaacgatg      600

acgcactact caagaactac gggctgctct actgcttcag gaaggacatg gacaaggtcg      660

agacattcct gcgcatcgtg cagtgccgct ctgtggaggg cagctgtggc ttctagctgc      720

ccgggtggca tccctgtgac ccctccccag tgcctctcct ggccctggaa gttgccactc      780

cagtgcccac cagccttgtc ctaataaaat taagttgcat ca                         822


<210>  21
<211>  195
<212>  PRT
<213>  homo sapiens

<400>  21

Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe 
1               5                   10                  15      


Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu 
            20                  25                  30          


Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala 
        35                  40                  45              


Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
    50                  55                  60                  


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
65                  70                  75                  80  


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
                85                  90                  95      


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
            100                 105                 110         


Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp 
        115                 120                 125             


Met Pro Lys Thr Gln Lys Tyr Gln Pro Pro Ser Thr Asn Lys Asn Thr 
    130                 135                 140                 


Lys Ser Gln Arg Arg Lys Gly Trp Pro Lys Thr His Pro Gly Gly Glu 
145                 150                 155                 160 


Gln Lys Glu Gly Thr Glu Ala Ser Leu Gln Ile Arg Gly Lys Lys Lys 
                165                 170                 175     


Glu Gln Arg Arg Glu Ile Gly Ser Arg Asn Ala Glu Cys Arg Gly Lys 
            180                 185                 190         


Lys Gly Lys 
        195 


<210>  22
<211>  70
<212>  PRT
<213>  homo sapiens

<400>  22

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
            20                  25                  30          


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
        35                  40                  45              


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
    50                  55                  60                  


Lys Pro Ala Lys Ser Ala 
65                  70  


<210>  23
<211>  725
<212>  DNA
<213>  homo sapiens

<400>  23
cttcagaagc aatgggaaaa atcagcagtc ttccaaccca attatttaag tgctgctttt       60

gtgatttctt gaaggtgaag atgcacacca tgtcctcctc gcatctcttc tacctggcgc      120

tgtgcctgct caccttcacc agctctgcca cggctggacc ggagacgctc tgcggggctg      180

agctggtgga tgctcttcag ttcgtgtgtg gagacagggg cttttatttc aacaagccca      240

cagggtatgg ctccagcagt cggagggcgc ctcagacagg tatcgtggat gagtgctgct      300

tccggagctg tgatctaagg aggctggaga tgtattgcgc acccctcaag cctgccaagt      360

cagctcgctc tgtccgtgcc cagcgccaca ccgacatgcc caagacccag aaggaagtac      420

atttgaagaa cgcaagtaga gggagtgcag gaaacaagaa ctacaggatg taggaagacc      480

ctcctgagga gtgaagagtg acatgccacc gcaggatcct ttgctctgca cgagttacct      540

gttaaacttt ggaacaccta ccaaaaaata agtttgataa catttaaaag atgggcgttt      600

cccccaatga aatacacaag taaacattcc aacattgtct ttaggagtga tttgcacctt      660

gcaaaaatgg tcctggagtt ggtagattgc tgttgatctt ttatcaataa tgttctatag      720

aaaag                                                                  725


<210>  24
<211>  411
<212>  PRT
<213>  homo sapiens

<400>  24

Met Ser Pro Ala Arg Leu Arg Pro Arg Leu His Phe Cys Leu Val Leu 
1               5                   10                  15      


Leu Leu Leu Leu Val Val Pro Ala Ala Trp Gly Cys Gly Pro Gly Arg 
            20                  25                  30          


Val Val Gly Ser Arg Arg Arg Pro Pro Arg Lys Leu Val Pro Leu Ala 
        35                  40                  45              


Tyr Lys Gln Phe Ser Pro Asn Val Pro Glu Lys Thr Leu Gly Ala Ser 
    50                  55                  60                  


Gly Arg Tyr Glu Gly Lys Ile Ala Arg Ser Ser Glu Arg Phe Lys Glu 
65                  70                  75                  80  


Leu Thr Pro Asn Tyr Asn Pro Asp Ile Ile Phe Lys Asp Glu Glu Asn 
                85                  90                  95      


Thr Gly Ala Asp Arg Leu Met Thr Gln Arg Cys Lys Asp Arg Leu Asn 
            100                 105                 110         


Ser Leu Ala Ile Ser Val Met Asn Gln Trp Pro Gly Val Lys Leu Arg 
        115                 120                 125             


Val Thr Glu Gly Trp Asp Glu Asp Gly His His Ser Glu Glu Ser Leu 
    130                 135                 140                 


His Tyr Glu Gly Arg Ala Val Asp Ile Thr Thr Ser Asp Arg Asp Arg 
145                 150                 155                 160 


Asn Lys Tyr Gly Leu Leu Ala Arg Leu Ala Val Glu Ala Gly Phe Asp 
                165                 170                 175     


Trp Val Tyr Tyr Glu Ser Lys Ala His Val His Cys Ser Val Lys Ser 
            180                 185                 190         


Glu His Ser Ala Ala Ala Lys Thr Gly Gly Cys Phe Pro Ala Gly Ala 
        195                 200                 205             


Gln Val Arg Leu Glu Ser Gly Ala Arg Val Ala Leu Ser Ala Val Arg 
    210                 215                 220                 


Pro Gly Asp Arg Val Leu Ala Met Gly Glu Asp Gly Ser Pro Thr Phe 
225                 230                 235                 240 


Ser Asp Val Leu Ile Phe Leu Asp Arg Glu Pro His Arg Leu Arg Ala 
                245                 250                 255     


Phe Gln Val Ile Glu Thr Gln Asp Pro Pro Arg Arg Leu Ala Leu Thr 
            260                 265                 270         


Pro Ala His Leu Leu Phe Thr Ala Asp Asn His Thr Glu Pro Ala Ala 
        275                 280                 285             


Arg Phe Arg Ala Thr Phe Ala Ser His Val Gln Pro Gly Gln Tyr Val 
    290                 295                 300                 


Leu Val Ala Gly Val Pro Gly Leu Gln Pro Ala Arg Val Ala Ala Val 
305                 310                 315                 320 


Ser Thr His Val Ala Leu Gly Ala Tyr Ala Pro Leu Thr Lys His Gly 
                325                 330                 335     


Thr Leu Val Val Glu Asp Val Val Ala Ser Cys Phe Ala Ala Val Ala 
            340                 345                 350         


Asp His His Leu Ala Gln Leu Ala Phe Trp Pro Leu Arg Leu Phe His 
        355                 360                 365             


Ser Leu Ala Trp Gly Ser Trp Thr Pro Gly Glu Gly Val His Trp Tyr 
    370                 375                 380                 


Pro Gln Leu Leu Tyr Arg Leu Gly Arg Leu Leu Leu Glu Glu Gly Ser 
385                 390                 395                 400 


Phe His Pro Leu Gly Met Ser Gly Ala Gly Ser 
                405                 410     


<210>  25
<211>  383
<212>  PRT
<213>  homo sapiens

<400>  25

Gly Pro Gly Arg Val Val Gly Ser Arg Arg Arg Pro Pro Arg Lys Leu 
1               5                   10                  15      


Val Pro Leu Ala Tyr Lys Gln Phe Ser Pro Asn Val Pro Glu Lys Thr 
            20                  25                  30          


Leu Gly Ala Ser Gly Arg Tyr Glu Gly Lys Ile Ala Arg Ser Ser Glu 
        35                  40                  45              


Arg Phe Lys Glu Leu Thr Pro Asn Tyr Asn Pro Asp Ile Ile Phe Lys 
    50                  55                  60                  


Asp Glu Glu Asn Thr Gly Ala Asp Arg Leu Met Thr Gln Arg Cys Lys 
65                  70                  75                  80  


Asp Arg Leu Asn Ser Leu Ala Ile Ser Val Met Asn Gln Trp Pro Gly 
                85                  90                  95      


Val Lys Leu Arg Val Thr Glu Gly Trp Asp Glu Asp Gly His His Ser 
            100                 105                 110         


Glu Glu Ser Leu His Tyr Glu Gly Arg Ala Val Asp Ile Thr Thr Ser 
        115                 120                 125             


Asp Arg Asp Arg Asn Lys Tyr Gly Leu Leu Ala Arg Leu Ala Val Glu 
    130                 135                 140                 


Ala Gly Phe Asp Trp Val Tyr Tyr Glu Ser Lys Ala His Val His Cys 
145                 150                 155                 160 


Ser Val Lys Ser Glu His Ser Ala Ala Ala Lys Thr Gly Gly Cys Phe 
                165                 170                 175     


Pro Ala Gly Ala Gln Val Arg Leu Glu Ser Gly Ala Arg Val Ala Leu 
            180                 185                 190         


Ser Ala Val Arg Pro Gly Asp Arg Val Leu Ala Met Gly Glu Asp Gly 
        195                 200                 205             


Ser Pro Thr Phe Ser Asp Val Leu Ile Phe Leu Asp Arg Glu Pro His 
    210                 215                 220                 


Arg Leu Arg Ala Phe Gln Val Ile Glu Thr Gln Asp Pro Pro Arg Arg 
225                 230                 235                 240 


Leu Ala Leu Thr Pro Ala His Leu Leu Phe Thr Ala Asp Asn His Thr 
                245                 250                 255     


Glu Pro Ala Ala Arg Phe Arg Ala Thr Phe Ala Ser His Val Gln Pro 
            260                 265                 270         


Gly Gln Tyr Val Leu Val Ala Gly Val Pro Gly Leu Gln Pro Ala Arg 
        275                 280                 285             


Val Ala Ala Val Ser Thr His Val Ala Leu Gly Ala Tyr Ala Pro Leu 
    290                 295                 300                 


Thr Lys His Gly Thr Leu Val Val Glu Asp Val Val Ala Ser Cys Phe 
305                 310                 315                 320 


Ala Ala Val Ala Asp His His Leu Ala Gln Leu Ala Phe Trp Pro Leu 
                325                 330                 335     


Arg Leu Phe His Ser Leu Ala Trp Gly Ser Trp Thr Pro Gly Glu Gly 
            340                 345                 350         


Val His Trp Tyr Pro Gln Leu Leu Tyr Arg Leu Gly Arg Leu Leu Leu 
        355                 360                 365             


Glu Glu Gly Ser Phe His Pro Leu Gly Met Ser Gly Ala Gly Ser 
    370                 375                 380             


<210>  26
<211>  2074
<212>  DNA
<213>  homo sapiens

<400>  26
atcagcccac caggagacct cgcccgccgc tcccccgggc tccccggcca tgtctcccgc       60

ccggctccgg ccccgactgc acttctgcct ggtcctgttg ctgctgctgg tggtgccggc      120

ggcatggggc tgcgggccgg gtcgggtggt gggcagccgc cggcgaccgc cacgcaaact      180

cgtgccgctc gcctacaagc agttcagccc caatgtgccc gagaagaccc tgggcgccag      240

cggacgctat gaaggcaaga tcgctcgcag ctccgagcgc ttcaaggagc tcacccccaa      300

ttacaatcca gacatcatct tcaaggacga ggagaacaca ggcgccgacc gcctcatgac      360

ccagcgctgc aaggaccgcc tgaactcgct ggctatctcg gtgatgaacc agtggcccgg      420

tgtgaagctg cgggtgaccg agggctggga cgaggacggc caccactcag aggagtccct      480

gcattatgag ggccgcgcgg tggacatcac cacatcagac cgcgaccgca ataagtatgg      540

actgctggcg cgcttggcag tggaggccgg ctttgactgg gtgtattacg agtcaaaggc      600

ccacgtgcat tgctccgtca agtccgagca ctcggccgca gccaagacgg gcggctgctt      660

ccctgccgga gcccaggtac gcctggagag tggggcgcgt gtggccttgt cagccgtgag      720

gccgggagac cgtgtgctgg ccatggggga ggatgggagc cccaccttca gcgatgtgct      780

cattttcctg gaccgcgagc ctcacaggct gagagccttc caggtcatcg agactcagga      840

ccccccacgc cgcctggcac tcacacccgc tcacctgctc tttacggctg acaatcacac      900

ggagccggca gcccgcttcc gggccacatt tgccagccac gtgcagcctg gccagtacgt      960

gctggtggct ggggtgccag gcctgcagcc tgcccgcgtg gcagctgtct ctacacacgt     1020

ggccctcggg gcctacgccc cgctcacaaa gcatgggaca ctggtggtgg aggatgtggt     1080

ggcatcctgc ttcgcggccg tggctgacca ccacctggct cagttggcct tctggcccct     1140

gagactcttt cacagcttgg catggggcag ctggaccccg ggggagggtg tgcattggta     1200

cccccagctg ctctaccgcc tggggcgtct cctgctagaa gagggcagct tccacccact     1260

gggcatgtcc ggggcaggga gctgaaagga ctccaccgct gccctcctgg aactgctgta     1320

ctgggtccag aagcctctca gccaggaggg agctggccct ggaagggacc tgagctgggg     1380

gacactggct cctgccatct cctctgccat gaagatacac cattgagact tgactgggca     1440

acaccagcgt cccccacccc cgtcgtggtg tagtcataga gctgcaagct gagctggcga     1500

ggggatggtt gttgacccct ctctcctaga gaccttgagg ctggcacggc gactcccaac     1560

tcagcctgct ctcactacga gttttcatac tctgcctccc ccattgggga gggcccattc     1620

catccatctt aggccccttt gggtgggctt gcgcctcagt tgatgctgct aaattccctg     1680

ggagccagca tggatctggc tggacccgat gctgtccaga actgggaagg ccacaggggt     1740

ggggcagcca tcccggccat tctgaggtat gacattcctc cccggccaca ctcctcaaga     1800

cacatccaga gactgttgct gtctgtgggc agagttctgt gttctggcca atgtgaccgt     1860

agtgccgggg actgggggag gtgggttgga tgtgcttgcc acccccccgg ctaagctccc     1920

ccttctgctg aaccatgatc cccaccccct ccgccggtca gtctcccata ccttatttat     1980

tggagtggag ggggaagccc atgggagaat tttggggatg ttttggtctt ttcttccttt     2040

tgtaataaaa attatttaag ttgttagagc caaa                                 2074


<210>  27
<211>  730
<212>  PRT
<213>  homo sapiens

<400>  27

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


Pro Arg Pro Gly Arg Pro Leu Asp Leu Ala Asp Tyr Thr Tyr Asp Leu 
            20                  25                  30          


Ala Glu Glu Asp Asp Ser Glu Pro Leu Asn Tyr Lys Asp Pro Cys Lys 
        35                  40                  45              


Ala Ala Ala Phe Leu Gly Asp Ile Ala Leu Asp Glu Glu Asp Leu Arg 
    50                  55                  60                  


Ala Phe Gln Val Gln Gln Ala Val Asp Leu Arg Arg His Thr Ala Arg 
65                  70                  75                  80  


Lys Ser Ser Ile Lys Ala Ala Val Pro Gly Asn Thr Ser Thr Pro Ser 
                85                  90                  95      


Cys Gln Ser Thr Asn Gly Gln Pro Gln Arg Gly Ala Cys Gly Arg Trp 
            100                 105                 110         


Arg Gly Arg Ser Arg Ser Arg Arg Ala Ala Thr Ser Arg Pro Glu Arg 
        115                 120                 125             


Val Trp Pro Asp Gly Val Ile Pro Phe Val Ile Gly Gly Asn Phe Thr 
    130                 135                 140                 


Gly Ser Gln Arg Ala Val Phe Arg Gln Ala Met Arg His Trp Glu Lys 
145                 150                 155                 160 


His Thr Cys Val Thr Phe Leu Glu Arg Thr Asp Glu Asp Ser Tyr Ile 
                165                 170                 175     


Val Phe Thr Tyr Arg Pro Cys Gly Cys Cys Ser Tyr Val Gly Arg Arg 
            180                 185                 190         


Gly Gly Gly Pro Gln Ala Ile Ser Ile Gly Lys Asn Cys Asp Lys Phe 
        195                 200                 205             


Gly Ile Val Val His Glu Leu Gly His Val Val Gly Phe Trp His Glu 
    210                 215                 220                 


His Thr Arg Pro Asp Arg Asp Arg His Val Ser Ile Val Arg Glu Asn 
225                 230                 235                 240 


Ile Gln Pro Gly Gln Glu Tyr Asn Phe Leu Lys Met Glu Pro Gln Glu 
                245                 250                 255     


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


Ala Arg Asn Thr Phe Ser Arg Gly Ile Phe Leu Asp Thr Ile Val Pro 
        275                 280                 285             


Lys Tyr Glu Val Asn Gly Val Lys Pro Pro Ile Gly Gln Arg Thr Arg 
    290                 295                 300                 


Leu Ser Lys Gly Asp Ile Ala Gln Ala Arg Lys Leu Tyr Lys Cys Pro 
305                 310                 315                 320 


Ala Cys Gly Glu Thr Leu Gln Asp Ser Thr Gly Asn Phe Ser Ser Pro 
                325                 330                 335     


Glu Tyr Pro Asn Gly Tyr Ser Ala His Met His Cys Val Trp Arg Ile 
            340                 345                 350         


Ser Val Thr Pro Gly Glu Lys Ile Ile Leu Asn Phe Thr Ser Leu Asp 
        355                 360                 365             


Leu Tyr Arg Ser Arg Leu Cys Trp Tyr Asp Tyr Val Glu Val Arg Asp 
    370                 375                 380                 


Gly Phe Trp Arg Lys Ala Pro Leu Arg Gly Arg Phe Cys Gly Ser Lys 
385                 390                 395                 400 


Leu Pro Glu Pro Ile Val Ser Thr Asp Ser Arg Leu Trp Val Glu Phe 
                405                 410                 415     


Arg Ser Ser Ser Asn Trp Val Gly Lys Gly Phe Phe Ala Val Tyr Glu 
            420                 425                 430         


Ala Ile Cys Gly Gly Asp Val Lys Lys Asp Tyr Gly His Ile Gln Ser 
        435                 440                 445             


Pro Asn Tyr Pro Asp Asp Tyr Arg Pro Ser Lys Val Cys Ile Trp Arg 
    450                 455                 460                 


Ile Gln Val Ser Glu Gly Phe His Val Gly Leu Thr Phe Gln Ser Phe 
465                 470                 475                 480 


Glu Ile Glu Arg His Asp Ser Cys Ala Tyr Asp Tyr Leu Glu Val Arg 
                485                 490                 495     


Asp Gly His Ser Glu Ser Ser Thr Leu Ile Gly Arg Tyr Cys Gly Tyr 
            500                 505                 510         


Glu Lys Pro Asp Asp Ile Lys Ser Thr Ser Ser Arg Leu Trp Leu Lys 
        515                 520                 525             


Phe Val Ser Asp Gly Ser Ile Asn Lys Ala Gly Phe Ala Val Asn Phe 
    530                 535                 540                 


Phe Lys Glu Val Asp Glu Cys Ser Arg Pro Asn Arg Gly Gly Cys Glu 
545                 550                 555                 560 


Gln Arg Cys Leu Asn Thr Leu Gly Ser Tyr Lys Cys Ser Cys Asp Pro 
                565                 570                 575     


Gly Tyr Glu Leu Ala Pro Asp Lys Arg Arg Cys Glu Ala Ala Cys Gly 
            580                 585                 590         


Gly Phe Leu Thr Lys Leu Asn Gly Ser Ile Thr Ser Pro Gly Trp Pro 
        595                 600                 605             


Lys Glu Tyr Pro Pro Asn Lys Asn Cys Ile Trp Gln Leu Val Ala Pro 
    610                 615                 620                 


Thr Gln Tyr Arg Ile Ser Leu Gln Phe Asp Phe Phe Glu Thr Glu Gly 
625                 630                 635                 640 


Asn Asp Val Cys Lys Tyr Asp Phe Val Glu Val Arg Ser Gly Leu Thr 
                645                 650                 655     


Ala Asp Ser Lys Leu His Gly Lys Phe Cys Gly Ser Glu Lys Pro Glu 
            660                 665                 670         


Val Ile Thr Ser Gln Tyr Asn Asn Met Arg Val Glu Phe Lys Ser Asp 
        675                 680                 685             


Asn Thr Val Ser Lys Lys Gly Phe Lys Ala His Phe Phe Ser Glu Lys 
    690                 695                 700                 


Arg Pro Ala Leu Gln Pro Pro Arg Gly Arg Pro His Gln Leu Lys Phe 
705                 710                 715                 720 


Arg Val Gln Lys Arg Asn Arg Thr Pro Gln 
                725                 730 


<210>  28
<211>  708
<212>  PRT
<213>  homo sapiens

<400>  28

Leu Asp Leu Ala Asp Tyr Thr Tyr Asp Leu Ala Glu Glu Asp Asp Ser 
1               5                   10                  15      


Glu Pro Leu Asn Tyr Lys Asp Pro Cys Lys Ala Ala Ala Phe Leu Gly 
            20                  25                  30          


Asp Ile Ala Leu Asp Glu Glu Asp Leu Arg Ala Phe Gln Val Gln Gln 
        35                  40                  45              


Ala Val Asp Leu Arg Arg His Thr Ala Arg Lys Ser Ser Ile Lys Ala 
    50                  55                  60                  


Ala Val Pro Gly Asn Thr Ser Thr Pro Ser Cys Gln Ser Thr Asn Gly 
65                  70                  75                  80  


Gln Pro Gln Arg Gly Ala Cys Gly Arg Trp Arg Gly Arg Ser Arg Ser 
                85                  90                  95      


Arg Arg Ala Ala Thr Ser Arg Pro Glu Arg Val Trp Pro Asp Gly Val 
            100                 105                 110         


Ile Pro Phe Val Ile Gly Gly Asn Phe Thr Gly Ser Gln Arg Ala Val 
        115                 120                 125             


Phe Arg Gln Ala Met Arg His Trp Glu Lys His Thr Cys Val Thr Phe 
    130                 135                 140                 


Leu Glu Arg Thr Asp Glu Asp Ser Tyr Ile Val Phe Thr Tyr Arg Pro 
145                 150                 155                 160 


Cys Gly Cys Cys Ser Tyr Val Gly Arg Arg Gly Gly Gly Pro Gln Ala 
                165                 170                 175     


Ile Ser Ile Gly Lys Asn Cys Asp Lys Phe Gly Ile Val Val His Glu 
            180                 185                 190         


Leu Gly His Val Val Gly Phe Trp His Glu His Thr Arg Pro Asp Arg 
        195                 200                 205             


Asp Arg His Val Ser Ile Val Arg Glu Asn Ile Gln Pro Gly Gln Glu 
    210                 215                 220                 


Tyr Asn Phe Leu Lys Met Glu Pro Gln Glu Val Glu Ser Leu Gly Glu 
225                 230                 235                 240 


Thr Tyr Asp Phe Asp Ser Ile Met His Tyr Ala Arg Asn Thr Phe Ser 
                245                 250                 255     


Arg Gly Ile Phe Leu Asp Thr Ile Val Pro Lys Tyr Glu Val Asn Gly 
            260                 265                 270         


Val Lys Pro Pro Ile Gly Gln Arg Thr Arg Leu Ser Lys Gly Asp Ile 
        275                 280                 285             


Ala Gln Ala Arg Lys Leu Tyr Lys Cys Pro Ala Cys Gly Glu Thr Leu 
    290                 295                 300                 


Gln Asp Ser Thr Gly Asn Phe Ser Ser Pro Glu Tyr Pro Asn Gly Tyr 
305                 310                 315                 320 


Ser Ala His Met His Cys Val Trp Arg Ile Ser Val Thr Pro Gly Glu 
                325                 330                 335     


Lys Ile Ile Leu Asn Phe Thr Ser Leu Asp Leu Tyr Arg Ser Arg Leu 
            340                 345                 350         


Cys Trp Tyr Asp Tyr Val Glu Val Arg Asp Gly Phe Trp Arg Lys Ala 
        355                 360                 365             


Pro Leu Arg Gly Arg Phe Cys Gly Ser Lys Leu Pro Glu Pro Ile Val 
    370                 375                 380                 


Ser Thr Asp Ser Arg Leu Trp Val Glu Phe Arg Ser Ser Ser Asn Trp 
385                 390                 395                 400 


Val Gly Lys Gly Phe Phe Ala Val Tyr Glu Ala Ile Cys Gly Gly Asp 
                405                 410                 415     


Val Lys Lys Asp Tyr Gly His Ile Gln Ser Pro Asn Tyr Pro Asp Asp 
            420                 425                 430         


Tyr Arg Pro Ser Lys Val Cys Ile Trp Arg Ile Gln Val Ser Glu Gly 
        435                 440                 445             


Phe His Val Gly Leu Thr Phe Gln Ser Phe Glu Ile Glu Arg His Asp 
    450                 455                 460                 


Ser Cys Ala Tyr Asp Tyr Leu Glu Val Arg Asp Gly His Ser Glu Ser 
465                 470                 475                 480 


Ser Thr Leu Ile Gly Arg Tyr Cys Gly Tyr Glu Lys Pro Asp Asp Ile 
                485                 490                 495     


Lys Ser Thr Ser Ser Arg Leu Trp Leu Lys Phe Val Ser Asp Gly Ser 
            500                 505                 510         


Ile Asn Lys Ala Gly Phe Ala Val Asn Phe Phe Lys Glu Val Asp Glu 
        515                 520                 525             


Cys Ser Arg Pro Asn Arg Gly Gly Cys Glu Gln Arg Cys Leu Asn Thr 
    530                 535                 540                 


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


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


Asn Gly Ser Ile Thr Ser Pro Gly Trp Pro Lys Glu Tyr Pro Pro Asn 
            580                 585                 590         


Lys Asn Cys Ile Trp Gln Leu Val Ala Pro Thr Gln Tyr Arg Ile Ser 
        595                 600                 605             


Leu Gln Phe Asp Phe Phe Glu Thr Glu Gly Asn Asp Val Cys Lys Tyr 
    610                 615                 620                 


Asp Phe Val Glu Val Arg Ser Gly Leu Thr Ala Asp Ser Lys Leu His 
625                 630                 635                 640 


Gly Lys Phe Cys Gly Ser Glu Lys Pro Glu Val Ile Thr Ser Gln Tyr 
                645                 650                 655     


Asn Asn Met Arg Val Glu Phe Lys Ser Asp Asn Thr Val Ser Lys Lys 
            660                 665                 670         


Gly Phe Lys Ala His Phe Phe Ser Glu Lys Arg Pro Ala Leu Gln Pro 
        675                 680                 685             


Pro Arg Gly Arg Pro His Gln Leu Lys Phe Arg Val Gln Lys Arg Asn 
    690                 695                 700                 


Arg Thr Pro Gln 
705             


<210>  29
<211>  2747
<212>  DNA
<213>  homo sapiens

<400>  29
gtcggaggga gggagggagg gagagaaaga aagagagaaa aagaaggaaa gggagaggga       60

gacggctgga gcccgaggac gagcgcggag ccgcggaccg agcggggggc gggagacagg      120

aaggagggag gcgagcagag ggaaggggaa gaggtcgggg agcgagggcg ggagcggtcg      180

cggtcgcgat cgagcaagca agcgggcgag aggacgccct cccctggcct ccagtgcgcc      240

gcttccctcg ccgccgcccc gccagcatgc ccggcgtggc ccgcctgccg ctgctgctcg      300

ggctgctgct gctcccgcgt cccggccggc cgctggactt ggccgactac acctatgacc      360

tggcggagga ggacgactcg gagcccctca actacaaaga cccctgcaag gcggctgcct      420

ttcttgggga cattgccctg gacgaagagg acctgagggc cttccaggta cagcaggctg      480

tggatctcag acggcacaca gctcgtaagt cctccatcaa agctgcagtt ccaggaaaca      540

cttctacccc cagctgccag agcaccaacg ggcagcctca gaggggagcc tgtgggagat      600

ggagaggtag atcccgtagc cggcgggcgg cgacgtcccg accagagcgt gtgtggcccg      660

atggggtcat cccctttgtc attgggggaa acttcactgg tagccagagg gcagtcttcc      720

ggcaggccat gaggcactgg gagaagcaca cctgtgtcac cttcctggag cgcactgacg      780

aggacagcta tattgtgttc acctatcgac cttgcgggtg ctgctcctac gtgggtcgcc      840

gcggcggggg cccccaggcc atctccatcg gcaagaactg tgacaagttc ggcattgtgg      900

tccacgagct gggccacgtc gtcggcttct ggcacgaaca cactcggcca gaccgggacc      960

gccacgtttc catcgttcgt gagaacatcc agccagggca ggagtataac ttcctgaaga     1020

tggagcctca ggaggtggag tccctggggg agacctatga cttcgacagc atcatgcatt     1080

acgctcggaa cacattctcc aggggcatct tcctggatac cattgtcccc aagtatgagg     1140

tgaacggggt gaaacctccc attggccaaa ggacacggct cagcaagggg gacattgccc     1200

aagcccgcaa gctttacaag tgcccagcct gtggagagac cctgcaagac agcacaggca     1260

acttctcctc ccctgaatac cccaatggct actctgctca catgcactgc gtgtggcgca     1320

tctctgtcac acccggggag aagatcatcc tgaacttcac gtccctggac ctgtaccgca     1380

gccgcctgtg ctggtacgac tatgtggagg tccgagatgg cttctggagg aaggcgcccc     1440

tccgaggccg cttctgcggg tccaaactcc ctgagcctat cgtctccact gacagccgcc     1500

tctgggttga attccgcagc agcagcaatt gggttggaaa gggcttcttt gcagtctacg     1560

aagccatctg cgggggtgat gtgaaaaagg actatggcca cattcaatcg cccaactacc     1620

cagacgatta ccggcccagc aaagtctgca tctggcggat ccaggtgtct gagggcttcc     1680

acgtgggcct cacattccag tcctttgaga ttgagcgcca cgacagctgt gcctacgact     1740

atctggaggt gcgcgacggg cacagtgaga gcagcaccct catcgggcgc tactgtggct     1800

atgagaagcc tgatgacatc aagagcacgt ccagccgcct ctggctcaag ttcgtctctg     1860

acgggtccat taacaaagcg ggctttgccg tcaacttttt caaagaggtg gacgagtgct     1920

ctcggcccaa ccgcgggggc tgtgagcagc ggtgcctcaa caccctgggc agctacaagt     1980

gcagctgtga ccccgggtac gagctggccc cagacaagcg ccgctgtgag gctgcttgtg     2040

gcggattcct caccaagctc aacggctcca tcaccagccc gggctggccc aaggagtacc     2100

cccccaacaa gaactgcatc tggcagctgg tggcccccac ccagtaccgc atctccctgc     2160

agtttgactt ctttgagaca gagggcaatg atgtgtgcaa gtacgacttc gtggaggtgc     2220

gcagtggact cacagctgac tccaagctgc atggcaagtt ctgtggttct gagaagcccg     2280

aggtcatcac ctcccagtac aacaacatgc gcgtggagtt caagtccgac aacaccgtgt     2340

ccaaaaaggg cttcaaggcc cacttcttct cagaaaagag gccagctctg cagccccctc     2400

ggggacgccc ccaccagctc aaattccgag tgcagaaaag aaaccggacc ccccagtgag     2460

gcctgccagg cctcccggac cccttgttac tcaggaacct caccttggac ggaatgggat     2520

gggggcttcg gtgcccacca accccccacc tccactctgc cattccggcc cacctccctc     2580

tggccggaca gaactggtgc tctcttctcc ccactgtgcc cgtccgcgga ccggggaccc     2640

ttccccgtgc cctaccccct cccattttga tggtgtctgt gacatttcct gttgtgaagt     2700

aaaagaggga cccctgcgtc ctgctccttt ctcttgcaga aaaaaaa                   2747


<210>  30
<211>  126
<212>  PRT
<213>  homo sapiens

<400>  30

Met His Leu Ser Gln Leu Leu Ala Cys Ala Leu Leu Leu Thr Leu Leu 
1               5                   10                  15      


Ser Leu Arg Pro Ser Glu Ala Lys Pro Gly Ala Pro Pro Lys Val Pro 
            20                  25                  30          


Arg Thr Pro Pro Ala Glu Glu Leu Ala Glu Pro Gln Ala Ala Gly Gly 
        35                  40                  45              


Gly Gln Lys Lys Gly Asp Lys Ala Pro Gly Gly Gly Gly Ala Asn Leu 
    50                  55                  60                  


Lys Gly Asp Arg Ser Arg Leu Leu Arg Asp Leu Arg Val Asp Thr Lys 
65                  70                  75                  80  


Ser Arg Ala Ala Trp Ala Arg Leu Leu Gln Glu His Pro Asn Ala Arg 
                85                  90                  95      


Lys Tyr Lys Gly Ala Asn Lys Lys Gly Leu Ser Lys Gly Cys Phe Gly 
            100                 105                 110         


Leu Lys Leu Asp Arg Ile Gly Ser Met Ser Gly Leu Gly Cys 
        115                 120                 125     


<210>  31
<211>  53
<212>  PRT
<213>  homo sapiens

<400>  31

Asp Leu Arg Val Asp Thr Lys Ser Arg Ala Ala Trp Ala Arg Leu Leu 
1               5                   10                  15      


Gln Glu His Pro Asn Ala Arg Lys Tyr Lys Gly Ala Asn Lys Lys Gly 
            20                  25                  30          


Leu Ser Lys Gly Cys Phe Gly Leu Lys Leu Asp Arg Ile Gly Ser Met 
        35                  40                  45              


Ser Gly Leu Gly Cys 
    50              


<210>  32
<211>  29
<212>  PRT
<213>  homo sapiens

<400>  32

Tyr Lys Gly Ala Asn Lys Lys Gly Leu Ser Lys Gly Cys Phe Gly Leu 
1               5                   10                  15      


Lys Leu Asp Arg Ile Gly Ser Met Ser Gly Leu Gly Cys 
            20                  25                  


<210>  33
<211>  22
<212>  PRT
<213>  homo sapiens

<400>  33

Gly Leu Ser Lys Gly Cys Phe Gly Leu Lys Leu Asp Arg Ile Gly Ser 
1               5                   10                  15      


Met Ser Gly Leu Gly Cys 
            20          


<210>  34
<211>  701
<212>  DNA
<213>  homo sapiens

<400>  34
cgcatccccc tgctggtctg cccgccgacc tgcgcgccct cgctgccgcc cgtgtgcgcc       60

cctcgacccc agcggcacca tgcatctctc ccagctgctg gcctgcgccc tgctgctcac      120

gctgctctcc ctccggccct ccgaagccaa gcccggggcg ccgccgaagg tcccgcgaac      180

cccgccggca gaggagctgg ccgagccgca ggctgcgggc ggcggtcaga agaagggcga      240

caaggctccc gggggcgggg gcgccaatct caagggcgac cggtcgcgac tgctccggga      300

cctgcgcgtg gacaccaagt cgcgggcagc gtgggctcgc cttctgcaag agcaccccaa      360

cgcgcgcaaa tacaaaggag ccaacaagaa gggcttgtcc aagggctgct tcggcctcaa      420

gctggaccga atcggctcca tgagcggcct gggatgttag tgcggcgccc cctggcggcg      480

gatcgggaac tggctccgtt gtgctgaggt catctttggt catcagcctc cagcatctgg      540

aaacacctcc aacgcaatgt ggcttttaca tttctttctt tctttctttt tttttcctgg      600

tactgggaat acacaacacc agctgtttta ttattatttg gggagggggt tgtgatttta      660

ttatttgttt ttttaaaatg aaaaataaaa agttatatat t                          701


<210>  35
<211>  370
<212>  PRT
<213>  homo sapiens

<400>  35

Met Gly Leu Trp Ala Leu Leu Pro Gly Trp Val Ser Ala Thr Leu Leu 
1               5                   10                  15      


Leu Ala Leu Ala Ala Leu Pro Ala Ala Leu Ala Ala Asn Ser Ser Gly 
            20                  25                  30          


Arg Trp Trp Gly Ile Val Asn Val Ala Ser Ser Thr Asn Leu Leu Thr 
        35                  40                  45              


Asp Ser Lys Ser Leu Gln Leu Val Leu Glu Pro Ser Leu Gln Leu Leu 
    50                  55                  60                  


Ser Arg Lys Gln Arg Arg Leu Ile Arg Gln Asn Pro Gly Ile Leu His 
65                  70                  75                  80  


Ser Val Ser Gly Gly Leu Gln Ser Ala Val Arg Glu Cys Lys Trp Gln 
                85                  90                  95      


Phe Arg Asn Arg Arg Trp Asn Cys Pro Thr Ala Pro Gly Pro His Leu 
            100                 105                 110         


Phe Gly Lys Ile Val Asn Arg Gly Cys Arg Glu Thr Ala Phe Ile Phe 
        115                 120                 125             


Ala Ile Thr Ser Ala Gly Val Thr His Ser Val Ala Arg Ser Cys Ser 
    130                 135                 140                 


Glu Gly Ser Ile Glu Ser Cys Thr Cys Asp Tyr Arg Arg Arg Gly Pro 
145                 150                 155                 160 


Gly Gly Pro Asp Trp His Trp Gly Gly Cys Ser Asp Asn Ile Asp Phe 
                165                 170                 175     


Gly Arg Leu Phe Gly Arg Glu Phe Val Asp Ser Gly Glu Lys Gly Arg 
            180                 185                 190         


Asp Leu Arg Phe Leu Met Asn Leu His Asn Asn Glu Ala Gly Arg Thr 
        195                 200                 205             


Thr Val Phe Ser Glu Met Arg Gln Glu Cys Lys Cys His Gly Met Ser 
    210                 215                 220                 


Gly Ser Cys Thr Val Arg Thr Cys Trp Met Arg Leu Pro Thr Leu Arg 
225                 230                 235                 240 


Ala Val Gly Asp Val Leu Arg Asp Arg Phe Asp Gly Ala Ser Arg Val 
                245                 250                 255     


Leu Tyr Gly Asn Arg Gly Ser Asn Arg Ala Ser Arg Ala Glu Leu Leu 
            260                 265                 270         


Arg Leu Glu Pro Glu Asp Pro Ala His Lys Pro Pro Ser Pro His Asp 
        275                 280                 285             


Leu Val Tyr Phe Glu Lys Ser Pro Asn Phe Cys Thr Tyr Ser Gly Arg 
    290                 295                 300                 


Leu Gly Thr Ala Gly Thr Ala Gly Arg Ala Cys Asn Ser Ser Ser Pro 
305                 310                 315                 320 


Ala Leu Asp Gly Cys Glu Leu Leu Cys Cys Gly Arg Gly His Arg Thr 
                325                 330                 335     


Arg Thr Gln Arg Val Thr Glu Arg Cys Asn Cys Thr Phe His Trp Cys 
            340                 345                 350         


Cys His Val Ser Cys Arg Asn Cys Thr His Thr Arg Val Leu His Glu 
        355                 360                 365             


Cys Leu 
    370 


<210>  36
<211>  343
<212>  PRT
<213>  homo sapiens

<400>  36

Ala Asn Ser Ser Gly Arg Trp Trp Gly Ile Val Asn Val Ala Ser Ser 
1               5                   10                  15      


Thr Asn Leu Leu Thr Asp Ser Lys Ser Leu Gln Leu Val Leu Glu Pro 
            20                  25                  30          


Ser Leu Gln Leu Leu Ser Arg Lys Gln Arg Arg Leu Ile Arg Gln Asn 
        35                  40                  45              


Pro Gly Ile Leu His Ser Val Ser Gly Gly Leu Gln Ser Ala Val Arg 
    50                  55                  60                  


Glu Cys Lys Trp Gln Phe Arg Asn Arg Arg Trp Asn Cys Pro Thr Ala 
65                  70                  75                  80  


Pro Gly Pro His Leu Phe Gly Lys Ile Val Asn Arg Gly Cys Arg Glu 
                85                  90                  95      


Thr Ala Phe Ile Phe Ala Ile Thr Ser Ala Gly Val Thr His Ser Val 
            100                 105                 110         


Ala Arg Ser Cys Ser Glu Gly Ser Ile Glu Ser Cys Thr Cys Asp Tyr 
        115                 120                 125             


Arg Arg Arg Gly Pro Gly Gly Pro Asp Trp His Trp Gly Gly Cys Ser 
    130                 135                 140                 


Asp Asn Ile Asp Phe Gly Arg Leu Phe Gly Arg Glu Phe Val Asp Ser 
145                 150                 155                 160 


Gly Glu Lys Gly Arg Asp Leu Arg Phe Leu Met Asn Leu His Asn Asn 
                165                 170                 175     


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


Cys His Gly Met Ser Gly Ser Cys Thr Val Arg Thr Cys Trp Met Arg 
        195                 200                 205             


Leu Pro Thr Leu Arg Ala Val Gly Asp Val Leu Arg Asp Arg Phe Asp 
    210                 215                 220                 


Gly Ala Ser Arg Val Leu Tyr Gly Asn Arg Gly Ser Asn Arg Ala Ser 
225                 230                 235                 240 


Arg Ala Glu Leu Leu Arg Leu Glu Pro Glu Asp Pro Ala His Lys Pro 
                245                 250                 255     


Pro Ser Pro His Asp Leu Val Tyr Phe Glu Lys Ser Pro Asn Phe Cys 
            260                 265                 270         


Thr Tyr Ser Gly Arg Leu Gly Thr Ala Gly Thr Ala Gly Arg Ala Cys 
        275                 280                 285             


Asn Ser Ser Ser Pro Ala Leu Asp Gly Cys Glu Leu Leu Cys Cys Gly 
    290                 295                 300                 


Arg Gly His Arg Thr Arg Thr Gln Arg Val Thr Glu Arg Cys Asn Cys 
305                 310                 315                 320 


Thr Phe His Trp Cys Cys His Val Ser Cys Arg Asn Cys Thr His Thr 
                325                 330                 335     


Arg Val Leu His Glu Cys Leu 
            340             


<210>  37
<211>  2284
<212>  DNA
<213>  homo sapiens

<400>  37
gcggtgccgc ccgccgtggc cgcctcagcc caccagccgg gaccgcgagc catgctgtcc       60

gccgcccgcc cccagggttg ttaaagccag actgcgaact ctcgccactg ccgccaccgc      120

cgcgtcccgt cccaccgtcg cgggcaacaa ccaaagtcgc cgcaactgca gcacagagcg      180

ggcaaagcca ggcaggccat ggggctctgg gcgctgttgc ctggctgggt ttctgctacg      240

ctgctgctgg cgctggccgc tctgcccgca gccctggctg ccaacagcag tggccgatgg      300

tggggtattg tgaacgtagc ctcctccacg aacctgctta cagactccaa gagtctgcaa      360

ctggtactcg agcccagtct gcagctgttg agccgcaaac agcggcgtct gatacgccaa      420

aatccgggga tcctgcacag cgtgagtggg gggctgcaga gtgccgtgcg cgagtgcaag      480

tggcagttcc ggaatcgccg ctggaactgt cccactgctc cagggcccca cctcttcggc      540

aagatcgtca accgaggctg tcgagaaacg gcgtttatct tcgctatcac ctccgccggg      600

gtcacccatt cggtggcgcg ctcctgctca gaaggttcca tcgaatcctg cacgtgtgac      660

taccggcggc gcggccccgg gggccccgac tggcactggg ggggctgcag cgacaacatt      720

gacttcggcc gcctcttcgg ccgggagttc gtggactccg gggagaaggg gcgggacctg      780

cgcttcctca tgaaccttca caacaacgag gcaggccgta cgaccgtatt ctccgagatg      840

cgccaggagt gcaagtgcca cgggatgtcc ggctcatgca cggtgcgcac gtgctggatg      900

cggctgccca cgctgcgcgc cgtgggcgat gtgctgcgcg accgcttcga cggcgcctcg      960

cgcgtcctgt acggcaaccg cggcagcaac cgcgcttcgc gggcggagct gctgcgcctg     1020

gagccggaag acccggccca caaaccgccc tccccccacg acctcgtcta cttcgagaaa     1080

tcgcccaact tctgcacgta cagcggacgc ctgggcacag caggcacggc agggcgcgcc     1140

tgtaacagct cgtcgcccgc gctggacggc tgcgagctgc tctgctgcgg caggggccac     1200

cgcacgcgca cgcagcgcgt caccgagcgc tgcaactgca ccttccactg gtgctgccac     1260

gtcagctgcc gcaactgcac gcacacgcgc gtactgcacg agtgtctgtg aggcgctgcg     1320

cggactcgcc cccaggaacg ctctcctcga gccctccccc aaacagactc gctagcactc     1380

aagacccggt tattcgccca cccgagtacc tccagtcaca ctccccgcgg ttcatacgca     1440

tcccatctct cccacttcct cctacctggg gactcctcaa accacttgcc tggggcggca     1500

tgaaccctct tgccatcctg atggacctgc cccggaccta cctccctccc tctccgcggg     1560

agaccccttg ttgcactgcc ccctgcttgg ccaggaggtg agagaaggat gggtcccctc     1620

cgccatgggg tcggctcctg atggtgtcat tctgcctgct ccatcgcgcc agcgacctct     1680

ctgcctctct tcttcccctt tgtcctgcgt tttctccggg tcctcctaag tcccttccta     1740

ttctcctgcc atgggtgcag accctgaacc cacacctggg catcagggcc tttctcctcc     1800

ccacctgtag ctgaagcagg aggttacagg gcaaaagggc agctgtgatg atgtggaaat     1860

gaggttgggg gaaccagcag aaatgccccc attctcccag tctctgtcgt ggagccattg     1920

aacagctgtg agccatgcct ccctgggcca cctcctaccc cttcctgtcc tgcctcctca     1980

tcagtgtgta aataatttgc actgaaacgt ggatacagag ccacgagttt ggatgttgta     2040

aataaaacta tttattgtgc tgggtcccag cctggtttgc aaagaccacc tccaacccaa     2100

cccaatccct ctccactctt ctctcctttc tccctgcagc cttttctggt ccctcttctc     2160

tcctcagttt ctcaaagatg cgtttgcctc ctggaatcag tatttccttc cactgtagct     2220

attagcggct cctcgccccc accagtgtag catcttcctc tgcagaataa aatctctatt     2280

ttta                                                                  2284


<210>  38
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  38

Gly Gly Gly Gly Ser 
1               5   


<210>  39
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  39

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  


<210>  40
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  peptide linker

<400>  40

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  41
<211>  544
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv-Fc-IGF-1 fusion protein

<400>  41

Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln 
1               5                   10                  15      


Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr 
            20                  25                  30          


Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys 
        35                  40                  45              


Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro 
    50                  55                  60                  


Leu Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu 
65                  70                  75                  80  


Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly 
                85                  90                  95      


Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly 
            100                 105                 110         


Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala 
        115                 120                 125             


Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys 
    130                 135                 140                 


Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 
145                 150                 155                 160 


Thr Ala Val Tyr Tyr Cys Ala Arg Gly Gln Gly Tyr Trp Phe Asp Pro 
                165                 170                 175     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
            180                 185                 190         


Gly Gly Gly Ala Ser Ser Gly Gly Gly Ser Asp Val Gln Leu Thr Gln 
        195                 200                 205             


Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 
    210                 215                 220                 


Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln 
225                 230                 235                 240 


Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu 
                245                 250                 255     


Glu Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
            260                 265                 270         


Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr 
        275                 280                 285             


Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Leu Thr Phe Gly Gly Gly Thr 
    290                 295                 300                 


Lys Leu Glu Ile Lys Arg Gly Gln Ala Gly Gln Gly Pro Asp Lys Thr 
305                 310                 315                 320 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
                325                 330                 335     


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
            340                 345                 350         


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
        355                 360                 365             


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
    370                 375                 380                 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
385                 390                 395                 400 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
                405                 410                 415     


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
            420                 425                 430         


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
        435                 440                 445             


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 
    450                 455                 460                 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
465                 470                 475                 480 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
                485                 490                 495     


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
            500                 505                 510         


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
        515                 520                 525             


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    530                 535                 540                 


<210>  42
<211>  547
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv-Fc-IGF-1 fusion protein

<400>  42

Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln 
1               5                   10                  15      


Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr 
            20                  25                  30          


Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys 
        35                  40                  45              


Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro 
    50                  55                  60                  


Leu Gly Gly Gly Gly Ser Gln Val Gln Leu Gln Gln Ser Gly Pro Gly 
65                  70                  75                  80  


Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly 
                85                  90                  95      


Asp Ser Val Ser Ser Asn Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser 
            100                 105                 110         


Pro Ser Arg Gly Leu Glu Trp Leu Gly Arg Thr Tyr Tyr Gly Ser Lys 
        115                 120                 125             


Trp Tyr Asn Asp Tyr Ala Pro Ser Val Lys Ser Arg Ile Ser Ile Asn 
    130                 135                 140                 


Pro Asp Thr Ser Lys Asn Gln Phe Ser Leu Gln Leu Asn Ser Val Thr 
145                 150                 155                 160 


Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Arg Gly Ile Trp Asn Ala 
                165                 170                 175     


Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly 
            180                 185                 190         


Gly Gly Ser Gly Gly Gly Ala Ser Gly Gly Gly Gly Ser Ser Ser Glu 
        195                 200                 205             


Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln Thr Val Arg 
    210                 215                 220                 


Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr 
225                 230                 235                 240 


Gln Gln Lys Pro Gly Gln Ala Pro Leu Leu Val Ile Tyr Asp Arg Asp 
                245                 250                 255     


Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly 
            260                 265                 270         


Asn Thr Ala Ser Leu Thr Ile Thr Gly Ala Gln Ala Glu Asp Glu Ala 
        275                 280                 285             


Asp Tyr Tyr Cys Gln Ser Tyr Asp Thr Ser Leu Ser Trp Val Phe Gly 
    290                 295                 300                 


Gly Gly Thr Gln Leu Thr Val Leu Gly Gly Gln Ala Gly Gln Gly Pro 
305                 310                 315                 320 


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
                325                 330                 335     


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            340                 345                 350         


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        355                 360                 365             


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    370                 375                 380                 


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
385                 390                 395                 400 


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                405                 410                 415     


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            420                 425                 430         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        435                 440                 445             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    450                 455                 460                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
465                 470                 475                 480 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                485                 490                 495     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            500                 505                 510         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        515                 520                 525             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    530                 535                 540                 


Pro Gly Lys 
545         


<210>  43
<211>  549
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv-Fc-IGF-1 fusion protein

<400>  43

Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln 
1               5                   10                  15      


Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr 
            20                  25                  30          


Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys 
        35                  40                  45              


Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro 
    50                  55                  60                  


Leu Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu 
65                  70                  75                  80  


Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly 
                85                  90                  95      


Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly 
            100                 105                 110         


Gln Gly Leu Glu Trp Met Gly Arg Ile Ile Pro Ile Leu Gly Ile Ala 
        115                 120                 125             


Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys 
    130                 135                 140                 


Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 
145                 150                 155                 160 


Thr Ala Val Tyr Tyr Cys Ala Arg Trp Gly Ser Gly Ser His Ala Phe 
                165                 170                 175     


Asp Ile Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly 
            180                 185                 190         


Gly Ser Gly Gly Gly Ala Ser Ser Gly Gly Gly Ser Ser Tyr Glu Leu 
        195                 200                 205             


Thr Gln Pro Pro Ser Thr Ser Gly Thr Pro Gly Gln Arg Val Ala Ile 
    210                 215                 220                 


Ser Cys Ser Gly Ala Ser Ser Asn Ile Gly Ser Asn Ala Val Ser Trp 
225                 230                 235                 240 


Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Ser Asn 
                245                 250                 255     


Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser 
            260                 265                 270         


Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg Ser Glu Asp Glu 
        275                 280                 285             


Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu Asn Gly Trp Val 
    290                 295                 300                 


Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly Gly Gln Ala Gly Gln 
305                 310                 315                 320 


Gly Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
                325                 330                 335     


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            340                 345                 350         


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        355                 360                 365             


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
    370                 375                 380                 


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
385                 390                 395                 400 


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                405                 410                 415     


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
            420                 425                 430         


Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        435                 440                 445             


Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
    450                 455                 460                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
465                 470                 475                 480 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                485                 490                 495     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            500                 505                 510         


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
        515                 520                 525             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    530                 535                 540                 


Leu Ser Pro Gly Lys 
545                 


<210>  44
<211>  534
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv-Fc-IGF-1 fusion protein

<400>  44

Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln 
1               5                   10                  15      


Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr 
            20                  25                  30          


Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys 
        35                  40                  45              


Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro 
    50                  55                  60                  


Leu Gly Gly Gly Gly Ser Gly Gln Ala Gly Gln Gly Pro Ala Pro Glu 
65                  70                  75                  80  


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                85                  90                  95      


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            100                 105                 110         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        115                 120                 125             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    130                 135                 140                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
145                 150                 155                 160 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                165                 170                 175     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            180                 185                 190         


Pro Gln Val Tyr Thr Ser Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        195                 200                 205             


Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    210                 215                 220                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
225                 230                 235                 240 


Thr Lys Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                245                 250                 255     


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


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        275                 280                 285             


Ser Leu Ser Pro Gly Lys Glu Val Gln Leu Val Gln Ser Gly Ala Glu 
    290                 295                 300                 


Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly 
305                 310                 315                 320 


Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly 
                325                 330                 335     


Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly Thr Ala 
            340                 345                 350         


Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys 
        355                 360                 365             


Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 
    370                 375                 380                 


Thr Ala Val Tyr Tyr Cys Ala Arg Gly Gln Gly Tyr Trp Phe Asp Pro 
385                 390                 395                 400 


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
                405                 410                 415     


Gly Gly Gly Ala Ser Ser Gly Gly Gly Ser Asp Val Gln Leu Thr Gln 
            420                 425                 430         


Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 
        435                 440                 445             


Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn Trp Tyr Gln Gln 
    450                 455                 460                 


Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Asp Ala Ser Asn Leu 
465                 470                 475                 480 


Glu Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                485                 490                 495     


Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr 
            500                 505                 510         


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


Lys Leu Glu Ile Lys Arg 
    530                 


<210>  45
<211>  537
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv-Fc-IGF-1 fusion protein

<400>  45

Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln 
1               5                   10                  15      


Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr 
            20                  25                  30          


Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys 
        35                  40                  45              


Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro 
    50                  55                  60                  


Leu Gly Gly Gly Gly Ser Gly Gln Ala Gly Gln Gly Pro Ala Pro Glu 
65                  70                  75                  80  


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                85                  90                  95      


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            100                 105                 110         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        115                 120                 125             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    130                 135                 140                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
145                 150                 155                 160 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                165                 170                 175     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            180                 185                 190         


Pro Gln Val Tyr Thr Ser Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        195                 200                 205             


Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    210                 215                 220                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
225                 230                 235                 240 


Thr Lys Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                245                 250                 255     


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


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        275                 280                 285             


Ser Leu Ser Pro Gly Lys Gln Val Gln Leu Gln Gln Ser Gly Pro Gly 
    290                 295                 300                 


Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Ala Ile Ser Gly 
305                 310                 315                 320 


Asp Ser Val Ser Ser Asn Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser 
                325                 330                 335     


Pro Ser Arg Gly Leu Glu Trp Leu Gly Arg Thr Tyr Tyr Gly Ser Lys 
            340                 345                 350         


Trp Tyr Asn Asp Tyr Ala Pro Ser Val Lys Ser Arg Ile Ser Ile Asn 
        355                 360                 365             


Pro Asp Thr Ser Lys Asn Gln Phe Ser Leu Gln Leu Asn Ser Val Thr 
    370                 375                 380                 


Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Arg Gly Ile Trp Asn Ala 
385                 390                 395                 400 


Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly 
                405                 410                 415     


Gly Gly Ser Gly Gly Gly Ala Ser Gly Gly Gly Gly Ser Ser Ser Glu 
            420                 425                 430         


Leu Thr Gln Asp Pro Ala Val Ser Val Ala Leu Gly Gln Thr Val Arg 
        435                 440                 445             


Ile Thr Cys Gln Gly Asp Ser Leu Arg Ser Tyr Tyr Ala Ser Trp Tyr 
    450                 455                 460                 


Gln Gln Lys Pro Gly Gln Ala Pro Leu Leu Val Ile Tyr Asp Arg Asp 
465                 470                 475                 480 


Asn Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser Ser Ser Gly 
                485                 490                 495     


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


Asp Tyr Tyr Cys Gln Ser Tyr Asp Thr Ser Leu Ser Trp Val Phe Gly 
        515                 520                 525             


Gly Gly Thr Gln Leu Thr Val Leu Gly 
    530                 535         


<210>  46
<211>  539
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv-Fc-IGF-1 fusion protein

<400>  46

Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln 
1               5                   10                  15      


Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr 
            20                  25                  30          


Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys 
        35                  40                  45              


Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro 
    50                  55                  60                  


Leu Gly Gly Gly Gly Ser Gly Gln Ala Gly Gln Gly Pro Ala Pro Glu 
65                  70                  75                  80  


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                85                  90                  95      


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            100                 105                 110         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        115                 120                 125             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    130                 135                 140                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
145                 150                 155                 160 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                165                 170                 175     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            180                 185                 190         


Pro Gln Val Tyr Thr Ser Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        195                 200                 205             


Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    210                 215                 220                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
225                 230                 235                 240 


Thr Lys Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                245                 250                 255     


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


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        275                 280                 285             


Ser Leu Ser Pro Gly Lys Glu Val Gln Leu Val Gln Ser Gly Ala Glu 
    290                 295                 300                 


Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly 
305                 310                 315                 320 


Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala Pro Gly 
                325                 330                 335     


Gln Gly Leu Glu Trp Met Gly Arg Ile Ile Pro Ile Leu Gly Ile Ala 
            340                 345                 350         


Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys 
        355                 360                 365             


Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 
    370                 375                 380                 


Thr Ala Val Tyr Tyr Cys Ala Arg Trp Gly Ser Gly Ser His Ala Phe 
385                 390                 395                 400 


Asp Ile Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly 
                405                 410                 415     


Gly Ser Gly Gly Gly Ala Ser Ser Gly Gly Gly Ser Ser Tyr Glu Leu 
            420                 425                 430         


Thr Gln Pro Pro Ser Thr Ser Gly Thr Pro Gly Gln Arg Val Ala Ile 
        435                 440                 445             


Ser Cys Ser Gly Ala Ser Ser Asn Ile Gly Ser Asn Ala Val Ser Trp 
    450                 455                 460                 


Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Ser Asn 
465                 470                 475                 480 


Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser 
                485                 490                 495     


Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg Ser Glu Asp Glu 
            500                 505                 510         


Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu Asn Gly Trp Val 
        515                 520                 525             


Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly 
    530                 535                 


<210>  47
<211>  227
<212>  PRT
<213>  homo sapiens

<400>  47

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys 
225         


<210>  48
<211>  217
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mutant Fc domain

<400>  48

Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
1               5                   10                  15      


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            20                  25                  30          


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                85                  90                  95      


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
            100                 105                 110         


Pro Arg Glu Pro Gln Val Tyr Thr Ser Pro Pro Ser Arg Asp Glu Leu 
        115                 120                 125             


Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr Pro 
    130                 135                 140                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
145                 150                 155                 160 


Tyr Lys Thr Thr Lys Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                165                 170                 175     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            180                 185                 190         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        195                 200                 205             


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215         


<210>  49
<211>  64
<212>  PRT
<213>  homo sapiens

<400>  49

Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe 
1               5                   10                  15      


Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly 
            20                  25                  30          


Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys 
        35                  40                  45              


Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu 
    50                  55                  60                  


<210>  50
<211>  90
<212>  PRT
<213>  homo sapiens

<400>  50

Lys Ser Val Lys Lys Arg Ser Val Ser Glu Ile Gln Leu Met His Asn 
1               5                   10                  15      


Leu Gly Lys His Leu Asn Ser Met Glu Arg Val Glu Trp Leu Arg Lys 
            20                  25                  30          


Lys Leu Gln Asp Val His Asn Phe Val Ala Leu Gly Ala Pro Leu Ala 
        35                  40                  45              


Pro Arg Asp Ala Gly Ser Gln Arg Pro Arg Lys Lys Glu Asp Asn Val 
    50                  55                  60                  


Leu Val Glu Ser His Glu Lys Ser Leu Gly Glu Ala Asp Lys Ala Asp 
65                  70                  75                  80  


Val Asn Val Leu Thr Lys Ala Lys Ser Gln 
                85                  90  


<210>  51
<211>  90
<212>  PRT
<213>  Homo sapiens

<400>  51

Lys Ser Val Lys Lys Arg Ser Val Ser Glu Ile Gln Leu Met His Asn 
1               5                   10                  15      


Leu Gly Lys His Leu Asn Ser Met Glu Arg Val Glu Trp Leu Arg Lys 
            20                  25                  30          


Lys Leu Gln Asp Val His Asn Phe Val Ala Leu Gly Ala Pro Leu Ala 
        35                  40                  45              


Pro Arg Asp Ala Gly Ser Gln Arg Pro Arg Lys Lys Glu Asp Asn Val 
    50                  55                  60                  


Leu Val Glu Ser His Glu Lys Ser Leu Gly Glu Ala Asp Lys Ala Asp 
65                  70                  75                  80  


Val Asn Val Leu Thr Lys Ala Lys Ser Gln 
                85                  90  


<210>  52
<211>  34
<212>  PRT
<213>  Homo sapiens

<400>  52

Ser Val Ser Glu Ile Gln Leu Met His Asn Leu Gly Lys His Leu Asn 
1               5                   10                  15      


Ser Met Glu Arg Val Glu Trp Leu Arg Lys Lys Leu Gln Asp Val His 
            20                  25                  30          


Asn Phe 
        


<210>  53
<211>  828
<212>  DNA
<213>  Homo sapiens

<400>  53
aaaagtcacc atttaagggg tctgcagtcc aattcatcag ttgtctttag tttactcagc       60

atcagctact aacatacctg aacgaagatc ttgttctaag acattgtatg tgaagatgat      120

acctgcaaaa gacatggcta aagttatgat tgtcatgttg gcaatttgtt ttcttacaaa      180

atcggatggg aaatctgtta agaagagatc tgtgagtgaa atacagctta tgcataacct      240

gggaaaacat ctgaactcga tggagagagt agaatggctg cgtaagaagc tgcaggatgt      300

gcacaatttt gttgcccttg gagctcctct agctcccaga gatgctggtt cccagaggcc      360

ccgaaaaaag gaagacaatg tcttggttga gagccatgaa aaaagtcttg gagaggcaga      420

caaagctgat gtgaatgtat taactaaagc taaatcccag tgaaaatgaa aacagatatt      480

gtcagagttc tgctctagac agtgtagggc aacaatacat gctgctaatt caaagctcta      540

ttaagatttc caagtgccaa tatttctgat ataacaaact acatgtaatc catcactagc      600

catgataact gcaattttaa ttgattattc tgattccact tttattcatt tgagttattt      660

taattatctt ttctattgtt tattcttttt aaagtatgtt attgcataat ttataaaaga      720

ataaaattgc acttttaaac ctctcttcta ccttaaaatg taaaacaaaa atgtaatgat      780

cataagtcta aataaatgaa gtatttctca ctcaaaaaaa aaaaaaaa                   828


