SEQUENCE LISTING

<110>   KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN

<120>   Fusion protein for enhancing intestinal regeneration

<130>   P070669GB

<141>   2017-05-24

<160>   41

<170>   SeqWin2010, version 1.0

<210>   1
<211>   1734
<212>   DNA
<213>   Artificial Sequence

<220>
<223>   hIgG1 Heavy chain anti-hGpa33/Rspo4 fusion

<400>   1
gaagtgcagc tgctggaaag cggcggagga ctggtgcagc ctggcggatc tctgagactg  60
agctgtgccg ccagcggctt cgccttcagc acctacgata tgagctgggt gcgccaggcc  120
cctggcaagg gactggaatg ggtggccaca atcagcagcg gcggcagcta cacctactac  180
ctggacagcg tgaagggccg gttcaccatc agccgggaca gcagcaagaa caccctgtac  240
ctgcagatga actccctgca ggccgaggac agcgccatct actactgtgc ccctaccacc  300
gtggtgccct tcgcctattg gggccaggga acactcgtga ccgtgtcctc tgctagcacc  360
aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg  420
gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca  480
ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac  540
tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc  600
aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt  660
gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc  720
ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca  780
tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac  840
ggcgtggagg tgcataatgc caagacaaag ccgcgggagc agtacaacag cacgtaccgt  900
gtggtcagcg tcctccccgt cctgcaccag gactggctga atggcaagga gtacaagtgc  960
aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg  1020
cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac  1080
caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg  1140
gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac  1200
ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac  1260
gtcttctcat gctccgtgat gcatgaggct ctgcactacc actacacgca gaaaagctta  1320
agcctgagcc ccggcaaaga ggccgctgcc agagaagctg ccgctagaga agccgctgct  1380
cgggaagctg ctgcaagagt gggaacaggc ctgggcggca attgcaccgg ctgcatcatc  1440
tgcagcgagg aaaacggctg cagcacctgt cagcagagac tgttcctgtt catcagaaga  1500
gagggcatcc ggcagtacgg caagtgcctg cacgattgcc cccctggcta cttcggcatc  1560
agaggccagg aagtgaaccg ctgcaagaag tgcggcgcca cttgcgagag ctgcttcagc  1620
caggacttct gcatcaggtg caagcggcag ttctacctgt acaagggcaa gtgtctgcct  1680
acctgccctc ctggcacact ggcccaccag aacaccagag aatgccaggg cgaa        1734

<210>   2
<211>   351
<212>   DNA
<213>   Artificial Sequence

<220>
<223>   Variable region hIgG1 Heavy chain anti hGpa33

<400>   2
gaagtgcagc tgctggaaag cggcggagga ctggtgcagc ctggcggatc tctgagactg  60
agctgtgccg ccagcggctt cgccttcagc acctacgata tgagctgggt gcgccaggcc  120
cctggcaagg gactggaatg ggtggccaca atcagcagcg gcggcagcta cacctactac  180
ctggacagcg tgaagggccg gttcaccatc agccgggaca gcagcaagaa caccctgtac  240
ctgcagatga actccctgca ggccgaggac agcgccatct actactgtgc ccctaccacc  300
gtggtgccct tcgcctattg gggccaggga acactcgtga ccgtgtcctc t           351

<210>   3
<211>   351
<212>   DNA
<213>   Artificial Sequence

<220>
<223>   CDR2-Mutated Variable region hIgG1 Heavy chain anti hGpa33

<400>   3
gaagtgcagc tgctggaaag cggcggagga ctggtgcagc ctggcggatc tctgagactg  60
agctgtgccg ccagcggctt cgccttcagc acctacgata tgagctgggt gcgccaggcc  120
cctggcaagg gactggaatg ggtggccaca atcagcaaca aggacaacag ctacgcaacc  180
gcatacgcag tgaagggccg gttcaccatc agccgggaca gcagcaagaa caccctgtac  240
ctgcagatga actccctgca ggccgaggac agcgccatct actactgtgc ccctaccacc  300
gtggtgccct tcgcctattg gggccaggga acactcgtga ccgtgtcctc t           351

<210>   4
<211>   45
<212>   DNA
<213>   Artificial Sequence

<220>
<223>   Linker

<400>   4
gaagctgccg ctagagaagc cgctgctcgg gaagctgctg caaga                  45

<210>   5
<211>   336
<212>   DNA
<213>   Artificial Sequence

<220>
<223>   Rspondin4 furin domains

<400>   5
gtgggaacag gcctgggcgg caattgcacc ggctgcatca tctgcagcga ggaaaacggc  60
tgcagcacct gtcagcagag actgttcctg ttcatcagaa gagagggcat ccggcagtac  120
ggcaagtgcc tgcacgattg cccccctggc tacttcggca tcagaggcca ggaagtgaac  180
cgctgcaaga agtgcggcgc cacttgcgag agctgcttca gccaggactt ctgcatcagg  240
tgcaagcggc agttctacct gtacaagggc aagtgtctgc ctacctgccc tcctggcaca  300
ctggcccacc agaacaccag agaatgccag ggcgaa                            336

<210>   6
<211>   656
<212>   DNA
<213>   Artificial Sequence

<220>
<223>   hIgG anti-Gpa33 L-chain

<400>   6
gacatccaga tgacccagtc cccctcctcc ctgtccgtgt ccgtgggcga ccgcgtgacc  60
atcacctgca aggcctccca gaacgtgcgc accgtggtgg cctggtacca gcagaagccc  120
ggcctggccc ccaagaccct gatctacctg gcctccaacc gccacaccgg cgtgccctcc  180
cgcttctccg gctccggctc cggcaccgac ttcaccttca ccatctcctc cctgcagccc  240
gaggacatcg ccacctactt ctgccagcag cactggtcct accccctgac cttcggccag  300
ggcaccaagg tggaggtgaa gcgccgtacg gtggctgcac catctgtctt catcttcccg  360
ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc  420
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc  480
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg  540
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag  600
ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttaggc ggccgc      656

<210>   7
<211>   578
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   hIgG1 Heavy chain anti-Gpa33/Rspo4 fusion

<400>   7
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      

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

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

Ala Thr Ile Ser Ser Gly Gly Ser Tyr Thr Tyr Tyr Leu Asp Ser Val 
    50                  55                  60                  

Lys Gly Arg Phe Thr Ile Ser Arg Asp Ser Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  

Leu Gln Met Asn Ser Leu Gln Ala Glu Asp Ser Ala Ile Tyr Tyr Cys 
                85                  90                  95      

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

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        115                 120                 125             

Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                165                 170                 175     

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            180                 185                 190         

Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
        195                 200                 205             

Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His 
    210                 215                 220                 

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
            260                 265                 270         

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             

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

Leu Pro Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
305                 310                 315                 320 

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
                325                 330                 335     

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
            340                 345                 350         

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        355                 360                 365             

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

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

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
                405                 410                 415     

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            420                 425                 430         

Tyr His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Glu Ala 
        435                 440                 445             

Ala Ala Arg Glu Ala Ala Ala Arg Glu Ala Ala Ala Arg Glu Ala Ala 
    450                 455                 460                 

Ala Arg Val Gly Thr Gly Leu Gly Gly Asn Cys Thr Gly Cys Ile Ile 
465                 470                 475                 480 

Cys Ser Glu Glu Asn Gly Cys Ser Thr Cys Gln Gln Arg Leu Phe Leu 
                485                 490                 495     

Phe Ile Arg Arg Glu Gly Ile Arg Gln Tyr Gly Lys Cys Leu His Asp 
            500                 505                 510         

Cys Pro Pro Gly Tyr Phe Gly Ile Arg Gly Gln Glu Val Asn Arg Cys 
        515                 520                 525             

Lys Lys Cys Gly Ala Thr Cys Glu Ser Cys Phe Ser Gln Asp Phe Cys 
    530                 535                 540                 

Ile Arg Cys Lys Arg Gln Phe Tyr Leu Tyr Lys Gly Lys Cys Leu Pro 
545                 550                 555                 560 

Thr Cys Pro Pro Gly Thr Leu Ala His Gln Asn Thr Arg Glu Cys Gln 
                565                 570                 575     

Gly Glu 
        

<210>   8
<211>   117
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Variable region hIgG1 Heavy chain anti hGpa33

<400>   8
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      

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

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

Ala Thr Ile Ser Ser Gly Gly Ser Tyr Thr Tyr Tyr Leu Asp Ser Val 
    50                  55                  60                  

Lys Gly Arg Phe Thr Ile Ser Arg Asp Ser Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  

Leu Gln Met Asn Ser Leu Gln Ala Glu Asp Ser Ala Ile Tyr Tyr Cys 
                85                  90                  95      

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

Val Thr Val Ser Ser 
        115         

<210>   9
<211>   117
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   CDR2-Mutated Variable region hIgG1 Heavy chain anti hGpa33

<400>   9
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      

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

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

Ala Thr Ile Ser Asn Lys Asp Asn Ser Tyr Ala Thr Ala Tyr Ala Val 
    50                  55                  60                  

Lys Gly Arg Phe Thr Ile Ser Arg Asp Ser Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  

Leu Gln Met Asn Ser Leu Gln Ala Glu Asp Ser Ala Ile Tyr Tyr Cys 
                85                  90                  95      

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

Val Thr Val Ser Ser 
        115         

<210>   10
<211>   20
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Linker

<400>   10
Glu Ala Ala Ala Arg Glu Ala Ala Ala Arg Glu Ala Ala Ala Arg Glu 
1               5                   10                  15      

Ala Ala Ala Arg 
            20  

<210>   11
<211>   112
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   hRspondin4 furin domains

<400>   11
Val Gly Thr Gly Leu Gly Gly Asn Cys Thr Gly Cys Ile Ile Cys Ser 
1               5                   10                  15      

Glu Glu Asn Gly Cys Ser Thr Cys Gln Gln Arg Leu Phe Leu Phe Ile 
            20                  25                  30          

Arg Arg Glu Gly Ile Arg Gln Tyr Gly Lys Cys Leu His Asp Cys Pro 
        35                  40                  45              

Pro Gly Tyr Phe Gly Ile Arg Gly Gln Glu Val Asn Arg Cys Lys Lys 
    50                  55                  60                  

Cys Gly Ala Thr Cys Glu Ser Cys Phe Ser Gln Asp Phe Cys Ile Arg 
65                  70                  75                  80  

Cys Lys Arg Gln Phe Tyr Leu Tyr Lys Gly Lys Cys Leu Pro Thr Cys 
                85                  90                  95      

Pro Pro Gly Thr Leu Ala His Gln Asn Thr Arg Glu Cys Gln Gly Glu 
            100                 105                 110         

<210>   12
<211>   215
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Amino acid sequence hIgG anti-Gpa33 L-chain

<400>   12
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly 
1               5                   10                  15      

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

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

Tyr Leu Ala Ser Asn Arg His 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 Phe Cys Gln Gln His Trp Ser Tyr Pro Leu 
                85                  90                  95      

Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg Arg Thr Val Ala 
            100                 105                 110         

Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
        115                 120                 125             

Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    130                 135                 140                 

Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
145                 150                 155                 160 

Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                165                 170                 175     

Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            180                 185                 190         

Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        195                 200                 205             

Ser Phe Asn Arg Gly Glu Cys 
    210                 215 

<210>   13
<211>   108
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Variable region hIgG1 Light chain anti hGpa33

<400>   13
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly 
1               5                   10                  15      

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

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

Tyr Leu Ala Ser Asn Arg His 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 Phe Cys Gln Gln His Trp Ser Tyr Pro Leu 
                85                  90                  95      

Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg 
            100                 105             

<210>   14
<211>   446
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Amino acid sequence hIgG anti-Gpa33 H-chain

<400>   14
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      

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

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

Ala Thr Ile Ser Ser Gly Gly Ser Tyr Thr Tyr Tyr Leu Asp Ser Val 
    50                  55                  60                  

Lys Gly Arg Phe Thr Ile Ser Arg Asp Ser Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  

Leu Gln Met Asn Ser Leu Gln Ala Glu Asp Ser Ala Ile Tyr Tyr Cys 
                85                  90                  95      

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

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        115                 120                 125             

Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 

Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 

Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                165                 170                 175     

Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            180                 185                 190         

Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
        195                 200                 205             

Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His 
    210                 215                 220                 

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
            260                 265                 270         

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             

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

Leu Pro Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
305                 310                 315                 320 

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
                325                 330                 335     

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
            340                 345                 350         

Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        355                 360                 365             

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

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

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
                405                 410                 415     

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            420                 425                 430         

Tyr His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445     

<210>   15
<211>   51
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Rspo-1 furin 1

<400>   15
Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu Cys Ser Glu 
1               5                   10                  15      

Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile Leu Leu Glu 
            20                  25                  30          

Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser Cys Pro Pro 
        35                  40                  45              

Gly Tyr Phe 
    50      

<210>   16
<211>   50
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Rspo-2 furin 1

<400>   16
Tyr Val Ser Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys Asp 
1               5                   10                  15      

Asn Gly Cys Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg Arg 
            20                  25                  30          

Glu Gly Met Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser Gly 
        35                  40                  45              

Tyr Tyr 
    50  

<210>   17
<211>   51
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Rspo-3 furin 1

<400>   17
Pro Asn Val Ser Gln Gly Cys Gln Gly Gly Cys Ala Thr Cys Ser Asp 
1               5                   10                  15      

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

Arg Ile Gly Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys Pro Ser 
        35                  40                  45              

Gly Tyr Tyr 
    50      

<210>   18
<211>   50
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Rspo-4 furin 1

<400>   18
Thr Gly Leu Gly Gly Asn Cys Thr Gly Cys Ile Ile Cys Ser Glu Glu 
1               5                   10                  15      

Asn Gly Cys Ser Thr Cys Gln Gln Arg Leu Phe Leu Phe Ile Arg Arg 
            20                  25                  30          

Glu Gly Ile Arg Gln Tyr Gly Lys Cys Leu His Asp Cys Pro Pro Gly 
        35                  40                  45              

Tyr Phe 
    50  

<210>   19
<211>   44
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Rspo-1 furin 2

<400>   19
Met Asn Lys Cys Ile Lys Cys Lys Ile Glu His Cys Glu Ala Cys Phe 
1               5                   10                  15      

Ser His Asn Phe Cys Thr Lys Cys Lys Glu Gly Leu Tyr Leu His Lys 
            20                  25                  30          

Gly Arg Cys Tyr Pro Ala Cys Pro Glu Gly Ser Ser 
        35                  40                  

<210>   20
<211>   44
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Rspo-2 furin 2

<400>   20
Met Asn Arg Cys Ala Arg Cys Arg Ile Glu Asn Cys Asp Ser Cys Phe 
1               5                   10                  15      

Ser Lys Asp Phe Cys Thr Lys Cys Lys Val Gly Phe Tyr Leu His Arg 
            20                  25                  30          

Gly Arg Cys Phe Asp Glu Cys Pro Asp Gly Phe Ala 
        35                  40                  

<210>   21
<211>   44
<212>   PRT
<213>   Rspo-3 furin 2

<400>   21
Asp Ile Asn Lys Cys Thr Lys Cys Lys Ala Asp Cys Asp Thr Cys Phe 
1               5                   10                  15      

Asn Lys Asn Phe Cys Thr Lys Cys Lys Ser Gly Phe Tyr Leu His Leu 
            20                  25                  30          

Gly Lys Cys Leu Asp Asn Cys Pro Glu Gly Leu Glu 
        35                  40                  

<210>   22
<211>   43
<212>   PRT
<213>   Rspo-4 furin 2

<400>   22
Val Asn Arg Cys Lys Lys Cys Gly Ala Thr Cys Glu Ser Cys Phe Ser 
1               5                   10                  15      

Gln Asp Phe Cys Ile Arg Cys Lys Arg Gln Phe Tyr Leu Tyr Lys Gly 
            20                  25                  30          

Lys Cys Leu Pro Thr Cys Pro Pro Gly Thr Leu 
        35                  40              

<210>   23
<211>   2910
<212>   RNA
<213>   Homo sapiens

<400>   23
attccctccc tggtgctcgc agaggactgg cccctctccg ggctgggagc tccggccgag  60
cggaggcgcg acggagagca ccagcgcagg gcagagagcc cggagcgacc ggccagagta  120
gggcatccgc tcgggtgctg cggagaacga gggcagctcc gagccgcccc ggaggaccga  180
tgcgccgggt ggggcgctgg ccccgagggc gtgagccgtc cgcagattga gcaacttggg  240
aacgggcggg cggagcgcag gcgagccggg cgcccaggac agtcccgcag cgggcgggtg  300
agcgggccgc gccctcgccc ctcccgggcc tgcccccgtc gcgactggca gcacgaagct  360
gagattgtgg tttcctggtg attcaggtgg gagtgggcca gaagatcacc gctggcaagg  420
actgggttgg tttttggagt agtccctgct gacgtgacaa aaagatctct catatgatat  480
tccgaggtat ctttgaggaa gtctctcttt gaggacctcc ctttgagctg atggagaact  540
gggctcccca caccctctct gtccccagct gagattatgg tggatttggg ctacggccca  600
ggcctgggcc tcctgctgct gacccagccc cagaggtgtt agcaagagcc gtgtgctatc  660
caccctcccc gagaccaccc ctccgaccag gggcctggag ctggcgcgtg actatgcggc  720
ttgggctgtg tgtggtggcc ctggttctga gctggacgca cctcaccatc agcagccggg  780
ggatcaaggg gaaaaggcag aggcggatca gtgccgaggg gagccaggcc tgtgccaaag  840
gctgtgagct ctgctctgaa gtcaacggct gcctcaagtg ctcacccaag ctgttcatcc  900
tgctggagag gaacgacatc cgccaggtgg gcgtctgctt gccgtcctgc ccacctggat  960
acttcgacgc ccgcaacccc gacatgaaca agtgcatcaa atgcaagatc gagcactgtg  1020
aggcctgctt cagccataac ttctgcacca agtgtaagga gggcttgtac ctgcacaagg  1080
gccgctgcta tccagcttgt cccgagggct cctcagctgc caatggcacc atggagtgca  1140
gtagtcctgc gcaatgtgaa atgagcgagt ggtctccgtg ggggccctgc tccaagaagc  1200
agcagctctg tggtttccgg aggggctccg aggagcggac acgcagggtg ctacatgccc  1260
ctgtggggga ccatgctgcc tgctctgaca ccaaggagac ccggaggtgc acagtgagga  1320
gagtgccgtg tcctgagggg cagaagagga ggaagggagg ccagggccgg cgggagaatg  1380
ccaacaggaa cctggccagg aaggagagca aggaggcggg tgctggctct cgaagacgca  1440
aggggcagca acagcagcag cagcaaggga cagtggggcc actcacatct gcagggcctg  1500
cctagggaca ctgtccagcc tccaggccca tgcagaaaga gttcagtgct actctgcgtg  1560
attcaagctt tcctgaactg gaacgtcggg ggcaaagcat acacacacac tccaatccat  1620
ccatgcatac atagacacaa gacacacacg ctcaaacccc tgtccacata tacaaccata  1680
catacttgca catgtgtgtt catgtacaca cgcagacaca gacaccacac acacacatac  1740
acacacacac acacacacac ctgaggccac cagaagacac ttccatccct cgggcccagc  1800
agtacacact tggtttccag agctcccagt ggacatgtca gagacaacac ttcccagcat  1860
ctgagaccaa actgcagagg ggagccttct ggagaagctg ctgggatcgg accagccact  1920
gtggcagatg ggagccaagc ttgaggactg ctggtgacct gggaagaaac cttcttccca  1980
tcctgttcag cactcccagc tgtgtgactt tatcgttgga gagtattgtt acccttccag  2040
gatacatatc agggttaacc tgactttgaa aactgcttaa aggtttattt caaattaaaa  2100
caaaaaaatc aacgacagca gtagacacag gcaccacatt cctttgcagg gtgtgagggt  2160
ttggcgaggt atgcgtagga gcaagaaggg acagggaatt tcaagagacc ccaaatagcc  2220
tgctcagtag agggtcatgc agacaaggaa gaaaacttag gggctgctct gacggtggta  2280
aacaggctgt ctatatcctt gttactcaga gcatggcccg gcagcagtgt tgtcacaggg  2340
cagcttgtta ggaatgagaa tctcaggtct cattccagac ctggtgagcc agagtctaaa  2400
ttttaagatt cctgatgatt ggcatgttac ccaaatttga gaagtgctgc tgtaattccc  2460
cttaaaggac gggagaaagg gccccggcca tcttgcagca ggagggattc tggtcagcta  2520
taaaggagga ctttccatct gggagaggca gaatctatat actgaagggc tagtggcact  2580
gccaggggaa gggagtgcgt aggcttccag tgatggttgg ggacaatcct gcccaaaggc  2640
agggcagtgg atggaataac tccttgtggc attctgaagt gtgtgccagg ctctggacta  2700
ggtgctaggt ttccagggag gagccaaaca cgggccttgc tcttgtggag cttagaggtt  2760
ggtggggaag aaaataggca tgcaccaagg aattgtacaa acacatatat aactacaaaa  2820
ggatggtgcc aagggcaggt gaccactggc atctatgctt agctatgaaa gtgaataaag  2880
cagaataaaa ataaaatact ttctctcagg                                   2910

<210>   24
<211>   263
<212>   PRT
<213>   Homo sapiens

<400>   24
Met Arg Leu Gly Leu Cys Val Val Ala Leu Val Leu Ser Trp Thr His 
1               5                   10                  15      

Leu Thr Ile Ser Ser Arg Gly Ile Lys Gly Lys Arg Gln Arg Arg Ile 
            20                  25                  30          

Ser Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu Cys Ser 
        35                  40                  45              

Glu Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile Leu Leu 
    50                  55                  60                  

Glu Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser Cys Pro 
65                  70                  75                  80  

Pro Gly Tyr Phe Asp Ala Arg Asn Pro Asp Met Asn Lys Cys Ile Lys 
                85                  90                  95      

Cys Lys Ile Glu His Cys Glu Ala Cys Phe Ser His Asn Phe Cys Thr 
            100                 105                 110         

Lys Cys Lys Glu Gly Leu Tyr Leu His Lys Gly Arg Cys Tyr Pro Ala 
        115                 120                 125             

Cys Pro Glu Gly Ser Ser Ala Ala Asn Gly Thr Met Glu Cys Ser Ser 
    130                 135                 140                 

Pro Ala Gln Cys Glu Met Ser Glu Trp Ser Pro Trp Gly Pro Cys Ser 
145                 150                 155                 160 

Lys Lys Gln Gln Leu Cys Gly Phe Arg Arg Gly Ser Glu Glu Arg Thr 
                165                 170                 175     

Arg Arg Val Leu His Ala Pro Val Gly Asp His Ala Ala Cys Ser Asp 
            180                 185                 190         

Thr Lys Glu Thr Arg Arg Cys Thr Val Arg Arg Val Pro Cys Pro Glu 
        195                 200                 205             

Gly Gln Lys Arg Arg Lys Gly Gly Gln Gly Arg Arg Glu Asn Ala Asn 
    210                 215                 220                 

Arg Asn Leu Ala Arg Lys Glu Ser Lys Glu Ala Gly Ala Gly Ser Arg 
225                 230                 235                 240 

Arg Arg Lys Gly Gln Gln Gln Gln Gln Gln Gln Gly Thr Val Gly Pro 
                245                 250                 255     

Leu Thr Ser Ala Gly Pro Ala 
            260             

<210>   25
<211>   3149
<212>   RNA
<213>   Homo sapiens

<400>   25
agcctagact tagatgcctt ggaccacagc accacctact tatagaagca tcccaagcct  60
cagccggtct gcatctccat cggaaagtgc gcttgccaca tcccttcgga tcacttcgtc  120
ctcccgagag cgttctgcct tctacagctc ggaaagaaag aaatcttagc tgtgaagtga  180
ccgtggagaa agcgcaggaa gcgacacaat tggttaggga ggcagagagt gtgagcgggc  240
gcaccccttg cctggggacc gcgctcgcgg gcggggacgg agcatcccag tggctgcacc  300
cgccgctccg cgctcctgcc tggcgtcgcc aaccccgcgg cggccgctgg aattccagag  360
ctgccaggcg ctcccagccg gtctcggcaa acttttcccc agcccacgtg ctaaccaagc  420
ggctcgcttc ccgagcccgg gatggagcac cgcgcctagg gaggccgcgc cgcccgagac  480
gtgcgcacgg ttcgtggcgg agagatgctg atcgcgctga actgaccggt gcggcccggg  540
ggtgagtggc gagtctccct ctgagtcctc cccagcagcg cggccggcgc cggctctttg  600
ggcgaaccct ccagttccta gactttgaga ggcgtctctc ccccgcccga ccgcccagat  660
gcagtttcgc cttttctcct ttgccctcat cattctgaac tgcatggatt acagccactg  720
ccaaggcaac cgatggagac gcagtaagcg agctagttat gtatcaaatc ccatttgcaa  780
gggttgtttg tcttgttcaa aggacaatgg gtgtagccga tgtcaacaga agttgttctt  840
cttccttcga agagaaggga tgcgccagta tggagagtgc ctgcattcct gcccatccgg  900
gtactatgga caccgagccc cagatatgaa cagatgtgca agatgcagaa tagaaaactg  960
tgattcttgc tttagcaaag acttttgtac caagtgcaaa gtaggctttt atttgcatag  1020
aggccgttgc tttgatgaat gtccagatgg ttttgcacca ttagaagaaa ccatggaatg  1080
tgtggaagga tgtgaagttg gtcattggag cgaatgggga acttgtagca gaaataatcg  1140
cacatgtgga tttaaatggg gtctggaaac cagaacacgg caaattgtta aaaagccagt  1200
gaaagacaca atactgtgtc caaccattgc tgaatccagg agatgcaaga tgacaatgag  1260
gcattgtcca ggagggaaga gaacaccaaa ggcgaaggag aagaggaaca agaaaaagaa  1320
aaggaagctg atagaaaggg cccaggagca acacagcgtc ttcctagcta cagacagagc  1380
taaccaataa aacaagagat ccggtagatt tttaggggtt tttgtttttg caaatgtgca  1440
caaagctact ctccactcct gcacactggt gtgcagcctt tgtgctgctc tgcccagtat  1500
ctgttcccag taacatggtg aaaggaagca ccaccagcat ggcccctgtg ttatttatgc  1560
tttgatttga atctggagac tgtgaaggca ggagtaagtg cacagcccgt gacttggctc  1620
agtgtgtgct gagagaatcc gtccccggca ccatggacat gctagaggtg tgaggctgca  1680
gaacaccgct ggaggacgga cttgtgccta tttatgtgaa agaagatgct tggcaggcaa  1740
tgcgctactc actcgtgacc tttatttctc acattgtgca ttttcaagga tatgtttgtg  1800
tggatatctg cttagtgtta ccacatggta ttctcagcat gttaccttca cactgttgtg  1860
cgatgaaact gcttttagct gaggatatgc tctggaaatt cctgctcagt ttcactgcag  1920
ccctaatatg tacatatact gcaggagcta catataaagc tcttatttac tgtatattta  1980
tgctttcttg tgggtaacaa gtcatacctg attaatatga tgccactttg tttctagtgg  2040
ttcctaaccc attgtctgat aaatgacttt tctagtttgg ggaattgaca cttgttttgt  2100
tgcctcttga aacttttttt ttttcccctc attgtgggct tatttctcat tgtaagggta  2160
ggataaacta gtttttgtat atagagtcaa atgaccagtg tcaaagagtt tgcatattgg  2220
gtagaccttc tccactccac atgtcccaca catatagata aagcagcagg cggcatctgg  2280
caatcagaag cccaaactgc ctttgagtct aagatgtgat gactttgatg aaacacaact  2340
gaaaacatga gggactatat ccagtcactt gtagccagtt tcacaggcca gctacagaat  2400
tgtccaaaca aacattattt ctgactgcaa tttttttccc ccaaatttaa agcaatccct  2460
ggctttaaat gacaaggcac ctaccaatgt tcttgggtca ctgaagaagc tactaccatg  2520
agcctgggca tagaatttta ggagataaaa ggatgaattt ctgtgactgc cagtcagatc  2580
ttaacaggtt tctgttgagc cagaatctgt ttcagatcca agatggagag gaacactatg  2640
gaaacttccc aggtgacttt cagagcagtt gtttcaaaca catcattgtc cttttagggg  2700
aaccagtttt tagaaggttg tgaattggct ttttcacaaa gcatgattat cttcctggct  2760
gatccaggag aaaattagaa cagaaaaata atggttgtgg attttgaaac aaagcaaggt  2820
aaagcctttt ttttttcacc ttgcattggc aaaactacct cttcagtgtt tttaactttt  2880
gattcaaaag catcttacca ataaggataa atatcatata catcgttatg aaaatattgc  2940
tatgagataa taagccacat atgaatgttg tatacaactt tagggtttac atttaatcct  3000
gaagtgttac ctcctttcat gtctatttac actattttcc catttactaa gtggggaggg  3060
ggtctcctta tatagtgctt catcgttaat aagtcaatac ctgttgttcc tgggatgttc  3120
ttttttgtgc attaaaaact tcaaaatta                                    3149

<210>   26
<211>   243
<212>   PRT
<213>   Homo sapiens

<400>   26
Met Gln Phe Arg Leu Phe Ser Phe Ala Leu Ile Ile Leu Asn Cys Met 
1               5                   10                  15      

Asp Tyr Ser His Cys Gln Gly Asn Arg Trp Arg Arg Ser Lys Arg Ala 
            20                  25                  30          

Ser Tyr Val Ser Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser Lys 
        35                  40                  45              

Asp Asn Gly Cys Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu Arg 
    50                  55                  60                  

Arg Glu Gly Met Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro Ser 
65                  70                  75                  80  

Gly Tyr Tyr Gly His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg Cys 
                85                  90                  95      

Arg Ile Glu Asn Cys Asp Ser Cys Phe Ser Lys Asp Phe Cys Thr Lys 
            100                 105                 110         

Cys Lys Val Gly Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu Cys 
        115                 120                 125             

Pro Asp Gly Phe Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu Gly 
    130                 135                 140                 

Cys Glu Val Gly His Trp Ser Glu Trp Gly Thr Cys Ser Arg Asn Asn 
145                 150                 155                 160 

Arg Thr Cys Gly Phe Lys Trp Gly Leu Glu Thr Arg Thr Arg Gln Ile 
                165                 170                 175     

Val Lys Lys Pro Val Lys Asp Thr Ile Leu Cys Pro Thr Ile Ala Glu 
            180                 185                 190         

Ser Arg Arg Cys Lys Met Thr Met Arg His Cys Pro Gly Gly Lys Arg 
        195                 200                 205             

Thr Pro Lys Ala Lys Glu Lys Arg Asn Lys Lys Lys Lys Arg Lys Leu 
    210                 215                 220                 

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

Ala Asn Gln 
            

<210>   27
<211>   4583
<212>   RNA
<213>   Homo sapiens

<400>   27
gcggccgccc cggcggctcc tggaaccccg gttcgcggcg atgccagcca ccccagcgaa  60
gccgccgcag ttcagtgctt ggataatttg aaagtacaat agttggtttc cctgtccacc  120
cgccccactt cgcttgccat cacagcacgc ctatcggatg tgagaggaga agtcccgctg  180
ctcgggcact gtctatatac gcctaacacc tacatatatt ttaaaaacat taaatataat  240
taacaatcaa aagaaagagg agaaaggaag ggaagcatta ctgggttact atgcacttgc  300
gactgatttc ttggcttttt atcattttga actttatgga atacatcggc agccaaaacg  360
cctcccgggg aaggcgccag cgaagaatgc atcctaacgt tagtcaaggc tgccaaggag  420
gctgtgcaac atgctcagat tacaatggat gtttgtcatg taagcccaga ctattttttg  480
ctctggaaag aattggcatg aagcagattg gagtatgtct ctcttcatgt ccaagtggat  540
attatggaac tcgatatcca gatataaata agtgtacaaa atgcaaagct gactgtgata  600
cctgtttcaa caaaaatttc tgcacaaaat gtaaaagtgg attttactta caccttggaa  660
agtgccttga caattgccca gaagggttgg aagccaacaa ccatactatg gagtgtgtca  720
gtattgtgca ctgtgaggtc agtgaatgga atccttggag tccatgcacg aagaagggaa  780
aaacatgtgg cttcaaaaga gggactgaaa cacgggtccg agaaataata cagcatcctt  840
cagcaaaggg taacctgtgt cccccaacaa atgagacaag aaagtgtaca gtgcaaagga  900
agaagtgtca gaagggagaa cgaggaaaaa aaggaaggga gaggaaaaga aaaaaaccta  960
ataaaggaga aagtaaagaa gcaatacctg acagcaaaag tctggaatcc agcaaagaaa  1020
tcccagagca acgagaaaac aaacagcagc agaagaagcg aaaagtccaa gataaacaga  1080
aatcggtatc agtcagcact gtacactaga gggttccatg agattattgt agactcatga  1140
tgctgctatc tcaaccagat gcccaggaca ggtgctctag ccattaggac cacaaatgga  1200
catgtcagtt attgctctgt ctaaacaaca ttcccagtag ttgctatatt cttcatacaa  1260
gcatagttaa caacaaagag ccaaaagatc aaagaaggga tactttcaga tggttgtctt  1320
gtgtgcttct ctgcattttt aaaagacaag acattcttgt acatattatc aataggctat  1380
aagatgtaac aacgaaatga tgacatctgg agaagaaaca tcttttcctt ataaaaatgt  1440
gttttcaagc tgttgtttta agaagcaaaa gatagttctg caaattcaaa gatacagtat  1500
cccttcaaaa caaataggag ttcagggaag agaaacatcc ttcaaaggac agtgttgttt  1560
tgaccgggag atctagagag tgctcagaat tagggcctgg catttggaat cacaggattt  1620
atcatcacag aaacaactgt tttaagatta gttccatcac tctcatcctg tatttttata  1680
agaaacacaa gagtgcatac cagaattgaa tataccatat gggattggag aaagacaaat  1740
gtggaagaaa tcatagagct ggagactact tttgtgcttt acaaaactgt gaaggattgt  1800
ggtcacctgg aacaggtctc caatctatgt tagcactatg tggctcagcc tctgttaccc  1860
cttggattat atatcaacct gtaaacatgt gcctgtaact tacttccaaa aacaaaatca  1920
tacttattag aagaaaattc tgattttata gaaaaaaaat agagcaagga gaatataaca  1980
tgtttgcaaa gtcatgtgtt ttctttctca atgagggaaa aacaatttta ttacctgctt  2040
aatggtccac ctggaactaa aagggatact attttctaac aaggtatatc tagtagggga  2100
gaaagccacc acaataaata tatttgttaa tagtttttca agttttgttc actctgtttt  2160
attgtttgtt ttattgagaa attcttactc ttagagactc atgaattaag aaagagaatt  2220
ctgctaactc agagaacctg gttcctatgt aattcagaat atattacatt tctcagtaat  2280
atttgttttt tgaatccacc tttatctgag ccaatggaga tttacttata gcgtattagg  2340
agatatttat tccattttct tattttaatc aacattctaa ttatagacac atgggcctcc  2400
ctagctgatt tcactgctcc cccttcattg cttagaaatg ggcatcattt cttgtatgtc  2460
agatccccct gcatcttcaa catttagtct tttcttctcc atattttcta tctgtggatc  2520
tctttagggg attgaagtca ccctagctga aggcctcacc agtgtttcac agaggacaca  2580
gcccacccct tgcaggagga ggtatctctg agtgtgcagc acagaatcgc atgacccacc  2640
ttaaccttcc tgttgtcatg gaaggatgca cggctgctct gtccactgtg attcctagcc  2700
ctctcaagat cactgctttc tgaagaattt gcaatgactc tggcttctgg ctgcttatct  2760
ctggacaccc gttctccacc agttgtacag ttcatgtaat ctacttggct taattgattt  2820
tccacttctc tcttcctctt ctaagatata aacattttaa atgatttatt cctgtttctt  2880
attctggtgt ttctttcctt gtccctatga gataagtgtc tcaactcact aaatctattc  2940
ccaatgtata aaataattct aattccattt tcagctaaaa catatattac caagaagaaa  3000
caaactttat cctacagaat gatgttaggt agaaatatgt ccccaggttt gagacctttc  3060
ggatgatttc atataccatc tttcttctga gtgttaccca gtcaagtata agtagccaaa  3120
ttatttttgc acatctttct gtttctcatg tcttcattta ttcaacaagc acttactggg  3180
aaggtctaca cctgcatagg caatgctgga aaaagggtta agtaaaccag gacatgacaa  3240
tggtggcaaa tgactatcag gtcttcccat gtgtttgact caaacttatt accctatggt  3300
ccttctgaca atggcagaag gtctgaatcc ttgatgctaa acttatataa aagtagaatt  3360
attacaaagg aaaaagaaat aaaaactaac attcattttc atatgttgga tgaaatataa  3420
atgaagaaaa agataacatc aattttaact gtaattctcc atccaccagt aacagatcct  3480
taagacaata gaatcataca gtattcaaac cagcagcctt ctcaaatttg agcaaaaact  3540
ctatcaacct ctggtaaagt tcctacacta gtcacagaag gtgttaactt tctactctga  3600
ttctgtctcc ataatggggt aaactgttga tagtttaccc catcaacaga tggtcggtaa  3660
attattgatt cgaagaatcg agagagtgca gcaacataaa tctgttaatg tctgatcaag  3720
ctcctgccct gttctccgaa ttcagcttca taattaaggg aaggcctgtt ttctatcctc  3780
agatttaggt tctagtagca gttgtgtaac cactagtgag tcacttaact cctctgggtc  3840
cccatttctc atgtgcaaca agaaagaggg gaactggaga tgatcactct agttccagac  3900
aagggaacat ttcacacttt gtttacttca gggtgatgtc cctgagtcct cattagtgac  3960
tgcgtccttt ggaagttatc ccaaccctgc ttttctcaaa agtgaaaatg tataggctct  4020
cagaggagac agatttaact ctgcttctct aatgttattg aattaaaagc tgttcacatt  4080
agtggttatt aaatattgaa ataacactgg gaagaaaaag catatataaa tacagctaaa  4140
aacaagaata gatattcatt ctcacaaagg gagacagcaa agaaaatgga aagtgcactg  4200
gtgctagcgt tagacagctt gtgttaatgt ctcaattctg ctactaactg gttgcagctt  4260
gtgtgacctt gggcacattg tatgatctcg cagaatatca tcccaaatct gcaaaatgga  4320
attggcatca tctcttttgc aagattgtta tgagaattaa aaggttcttc attcaatata  4380
ataataaata ttttgtatat aaatgaatat caattaaaag ttatgactaa ttccacaagt  4440
caaacatata aattttattt cttgattcat gatatgtgat agtattcata aaaatgtaca  4500
tgcatgataa tttcaaggaa taagtatata tgtgagaatc atggaaatga aattaataat  4560
attaactagt aattaaattg taa                                          4583

<210>   28
<211>   272
<212>   PRT
<213>   Homo sapiens

<400>   28
Met His Leu Arg Leu Ile Ser Trp Leu Phe Ile Ile Leu Asn Phe Met 
1               5                   10                  15      

Glu Tyr Ile Gly Ser Gln Asn Ala Ser Arg Gly Arg Arg Gln Arg Arg 
            20                  25                  30          

Met His Pro Asn Val Ser Gln Gly Cys Gln Gly Gly Cys Ala Thr Cys 
        35                  40                  45              

Ser Asp Tyr Asn Gly Cys Leu Ser Cys Lys Pro Arg Leu Phe Phe Ala 
    50                  55                  60                  

Leu Glu Arg Ile Gly Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys 
65                  70                  75                  80  

Pro Ser Gly Tyr Tyr Gly Thr Arg Tyr Pro Asp Ile Asn Lys Cys Thr 
                85                  90                  95      

Lys Cys Lys Ala Asp Cys Asp Thr Cys Phe Asn Lys Asn Phe Cys Thr 
            100                 105                 110         

Lys Cys Lys Ser Gly Phe Tyr Leu His Leu Gly Lys Cys Leu Asp Asn 
        115                 120                 125             

Cys Pro Glu Gly Leu Glu Ala Asn Asn His Thr Met Glu Cys Val Ser 
    130                 135                 140                 

Ile Val His Cys Glu Val Ser Glu Trp Asn Pro Trp Ser Pro Cys Thr 
145                 150                 155                 160 

Lys Lys Gly Lys Thr Cys Gly Phe Lys Arg Gly Thr Glu Thr Arg Val 
                165                 170                 175     

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

Thr Asn Glu Thr Arg Lys Cys Thr Val Gln Arg Lys Lys Cys Gln Lys 
        195                 200                 205             

Gly Glu Arg Gly Lys Lys Gly Arg Glu Arg Lys Arg Lys Lys Pro Asn 
    210                 215                 220                 

Lys Gly Glu Ser Lys Glu Ala Ile Pro Asp Ser Lys Ser Leu Glu Ser 
225                 230                 235                 240 

Ser Lys Glu Ile Pro Glu Gln Arg Glu Asn Lys Gln Gln Gln Lys Lys 
                245                 250                 255     

Arg Lys Val Gln Asp Lys Gln Lys Ser Val Ser Val Ser Thr Val His 
            260                 265                 270         

<210>   29
<211>   2725
<212>   RNA
<213>   Homo sapiens

<400>   29
gcccacagca gcccccgcgc ccgccgtgcc gccgccggga cgtggggccc ttgggccgtc  60
gggccgcctg gggagcgcca gcccggatcc ggctgcccag atgcgggcgc cactctgcct  120
gctcctgctc gtcgcccacg ccgtggacat gctcgccctg aaccgaagga agaagcaagt  180
gggcactggc ctggggggca actgcacagg ctgtatcatc tgctcagagg agaacggctg  240
ttccacctgc cagcagaggc tcttcctgtt catccgccgg gaaggcatcc gccagtacgg  300
caagtgcctg cacgactgtc cccctgggta cttcggcatc cgcggccagg aggtcaacag  360
gtgcaaaaaa tgtggggcca cttgtgagag ctgcttcagc caggacttct gcatccggtg  420
caagaggcag ttttacttgt acaaggggaa gtgtctgccc acctgcccgc cgggcacttt  480
ggcccaccag aacacacggg agtgccaggg ggagtgtgaa ctgggtccct ggggcggctg  540
gagcccctgc acacacaatg gaaagacctg cggctcggct tggggcctgg agagccgggt  600
acgagaggct ggccgggctg ggcatgagga ggcagccacc tgccaggtgc tttctgagtc  660
aaggaaatgt cccatccaga ggccctgccc aggagagagg agccccggcc agaagaaggg  720
caggaaggac cggcgcccac gcaaggacag gaagctggac cgcaggctgg acgtgaggcc  780
gcgccagccc ggcctgcagc cctgaccgcc ggctctcccg actctctggt cctagtcctc  840
ggcccctgca cacctcctcc tgctccttct cctcctctcc tcttactctt tctcctctgt  900
cttctccatt tgtcctctct ttctttccac ccttctatca tttttctgtc agtctacctt  960
ccctttcttt ttctttttta tttcctttat ttcttccacc tccattctcc tctcctttct  1020
ccctccctcc ttcccttcct tcctcttctt tctcacttat cttttatctt tccttttctt  1080
tcttcctgtg tttcttcctg tccttcaccg catccttctc tctctccctc ctcttgtctc  1140
cctctcacac acactttaag agggaccatg agcctgtgcc ctcccctgca gctttctcta  1200
tctacaactt aaagaaagca aacatctttt cccaggcctt tccctgaccc catctttgca  1260
gagaaagggt ttccagaggg caaagctggg acacagcaca ggtgaatcct gaaggccctg  1320
cttctgctct gggggaggct ccaggaccct gagctgtgag cacctggttc tctggacagt  1380
ccccagaggc catttccaca gccttcagcc accagccacc ccgaggagct ggctggacaa  1440
ggctccaggg cttccagagg cctggcttgg acacctcccc cagctggccg tggagggtca  1500
caacctggcc tctgggtggg cagccagccc tggagggcat cctctgcaag ctgcctgcca  1560
ccctcatcgg cactccccca caggcctccc tctcatgggt tccatgcccc tttttcccaa  1620
gccggatcag gtgagctgtc actgctgggg gatccacctg cccagcccag aagaggccac  1680
tgaaacggaa aggaaagctg agattatcca gcagctctgt tccccacctc agcgcttcct  1740
gcccatgtgg ggaaacaggt ctgagaagga aggggcttgc ccagggtcac acaggaagcc  1800
ttcaggctct gcttctgcct gatggctctg ctcagcacat tcacggtgga gaggagaatt  1860
tgggggtcac ttgagggggg aaatgtaggg aattgtgggt ggggagcaag ggaagatccg  1920
tgcactcgtc cacacccacc accacactcg ctgacaccca cccccacacg ctgacaccca  1980
cccccacact tgcccacacc catcaccgca ctcgcccaca cccaccacca cactgcccca  2040
cacccaccac cacactcccc cacacccacc accacactcg cccacaccca ccaccagtga  2100
cttgagcatc tgtgcttcgc tgtgacgccc ctcgccctag gcaggaacga cgctgggagg  2160
agtctccagg tcagacccag cttggaagca agtctgtcct cactgcctat ccttctgcca  2220
tcataacacc cccttcctgc tctgctcccc ggaatcctca gaaacgggat ttgtatttgc  2280
cgtgactggt tggcctgaac acgtagggct ccgtgactgg gacaggaatg ggcaggagaa  2340
gcaagagtcg gagctccaag gggcccaggg gtggcctggg gaaggaagat ggtcagcagg  2400
ctgggggaga ggctctaggt gatgaaatat tacattcccg accccaagag agcacccacc  2460
ctcagacctg ccctccacct ggcagctggg gagccctggc ctgaaccccc ccctcccagc  2520
aggcccaccc tctctctgac ttccctgctc tcacctcccc gagaacagct agagccccct  2580
cctccgcctg gccaggccac cagcttctct tctgcaaacg tttgtgcctc tgaaatgctc  2640
cgttgttatt gtttcaagac cctaactttt ttttaaaact ttcttaataa agggaaaaga  2700
aacttgtaaa aaaaaaaaaa aaaaa                                        2725

<210>   30
<211>   234
<212>   PRT
<213>   Homo sapiens

<400>   30
Met Arg Ala Pro Leu Cys Leu Leu Leu Leu Val Ala His Ala Val Asp 
1               5                   10                  15      

Met Leu Ala Leu Asn Arg Arg Lys Lys Gln Val Gly Thr Gly Leu Gly 
            20                  25                  30          

Gly Asn Cys Thr Gly Cys Ile Ile Cys Ser Glu Glu Asn Gly Cys Ser 
        35                  40                  45              

Thr Cys Gln Gln Arg Leu Phe Leu Phe Ile Arg Arg Glu Gly Ile Arg 
    50                  55                  60                  

Gln Tyr Gly Lys Cys Leu His Asp Cys Pro Pro Gly Tyr Phe Gly Ile 
65                  70                  75                  80  

Arg Gly Gln Glu Val Asn Arg Cys Lys Lys Cys Gly Ala Thr Cys Glu 
                85                  90                  95      

Ser Cys Phe Ser Gln Asp Phe Cys Ile Arg Cys Lys Arg Gln Phe Tyr 
            100                 105                 110         

Leu Tyr Lys Gly Lys Cys Leu Pro Thr Cys Pro Pro Gly Thr Leu Ala 
        115                 120                 125             

His Gln Asn Thr Arg Glu Cys Gln Gly Glu Cys Glu Leu Gly Pro Trp 
    130                 135                 140                 

Gly Gly Trp Ser Pro Cys Thr His Asn Gly Lys Thr Cys Gly Ser Ala 
145                 150                 155                 160 

Trp Gly Leu Glu Ser Arg Val Arg Glu Ala Gly Arg Ala Gly His Glu 
                165                 170                 175     

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

Gln Arg Pro Cys Pro Gly Glu Arg Ser Pro Gly Gln Lys Lys Gly Arg 
        195                 200                 205             

Lys Asp Arg Arg Pro Arg Lys Asp Arg Lys Leu Asp Arg Arg Leu Asp 
    210                 215                 220                 

Val Arg Pro Arg Gln Pro Gly Leu Gln Pro 
225                 230                 

<210>   31
<211>   11
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   L-chain Gpa33 antibody CDR1

<400>   31
Lys Ala Ser Gln Asn Val Arg Thr Val Val Ala 
1               5                   10      

<210>   32
<211>   7
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   L-chain Gpa33 antibody CDR2

<400>   32
Leu Ala Ser Asn Arg His Thr 
1               5           

<210>   33
<211>   8
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   L-chain Gpa33 antibody CDR3

<400>   33
Gln His Trp Ser Tyr Pro Leu Thr 
1               5               

<210>   34
<211>   9
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   H-chain Gpa33 antibody CDR1

<400>   34
Phe Ala Phe Ser Thr Tyr Asp Met Ser 
1               5                   

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

<220>
<223>   H-chain Gpa33 antibody CDR2

<400>   35
Thr Ile Ser Ser Gly Gly Ser Tyr Thr Tyr Tyr Leu Asp Ser Val Lys 
1               5                   10                  15      

Gly 
    

<210>   36
<211>   9
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   H-chain Gpa33 antibody CDR3

<400>   36
Pro Thr Thr Val Val Pro Phe Ala Tyr 
1               5                   

<210>   37
<211>   72
<212>   PRT
<213>   Peptide encoded by mouse Gpa33 as in Figure 3C

<400>   37
Glu Arg Val Val Thr Trp Asn Phe Val Thr Lys Lys Tyr Ile Tyr Gly 
1               5                   10                  15      

Asn Arg Tyr Glu Asn Arg Val Arg Val Ser Asn Asp Ala Glu Leu Ser 
            20                  25                  30          

Asn Ala Ser Ile Thr Ile Asp Gln Leu Thr Met Asp Asp Asn Gly Thr 
        35                  40                  45              

Tyr Glu Cys Ser Val Ser Leu Met Ser Asp Gln Asp Val Asn Ala Lys 
    50                  55                  60                  

Ser Arg Val Arg Leu Leu Val Leu 
65                  70          

<210>   38
<211>   72
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   Peptide encoded by human Gpa33 as in Figure 3C

<400>   38
Glu Arg Val Val Ile Trp Pro Phe Ser Asn Lys Asn Tyr Ile His Gly 
1               5                   10                  15      

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

Asp Ala Ser Ile Thr Ile Asp Gln Leu Thr Met Ala Asp Asn Gly Thr 
        35                  40                  45              

Tyr Glu Cys Ser Val Ser Leu Met Ser Asp Leu Glu Gly Asn Thr Lys 
    50                  55                  60                  

Ser Arg Val Arg Leu Leu Val Leu 
65                  70          

<210>   39
<211>   115
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   hRspondin1 furin domains

<400>   39
Ile Ser Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu Cys 
1               5                   10                  15      

Ser Glu Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile Leu 
            20                  25                  30          

Leu Glu Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser Cys 
        35                  40                  45              

Pro Pro Gly Tyr Phe Asp Ala Arg Asn Pro Asp Met Asn Lys Cys Ile 
    50                  55                  60                  

Lys Cys Lys Ile Glu His Cys Glu Ala Cys Phe Ser His Asn Phe Cys 
65                  70                  75                  80  

Thr Lys Cys Lys Glu Gly Leu Tyr Leu His Lys Gly Arg Cys Tyr Pro 
                85                  90                  95      

Ala Cys Pro Glu Gly Ser Ser Ala Ala Asn Gly Thr Met Glu Cys Ser 
            100                 105                 110         

Ser Pro Ala 
        115 

<210>   40
<211>   113
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   hRspondin2 furin domains

<400>   40
Ala Ser Tyr Val Ser Asn Pro Ile Cys Lys Gly Cys Leu Ser Cys Ser 
1               5                   10                  15      

Lys Asp Asn Gly Cys Ser Arg Cys Gln Gln Lys Leu Phe Phe Phe Leu 
            20                  25                  30          

Arg Arg Glu Gly Met Arg Gln Tyr Gly Glu Cys Leu His Ser Cys Pro 
        35                  40                  45              

Ser Gly Tyr Tyr Gly His Arg Ala Pro Asp Met Asn Arg Cys Ala Arg 
    50                  55                  60                  

Cys Arg Ile Glu Asn Cys Asp Ser Cys Phe Ser Lys Asp Phe Cys Thr 
65                  70                  75                  80  

Lys Cys Lys Val Gly Phe Tyr Leu His Arg Gly Arg Cys Phe Asp Glu 
                85                  90                  95      

Cys Pro Asp Gly Phe Ala Pro Leu Glu Glu Thr Met Glu Cys Val Glu 
            100                 105                 110         

Gly 
    

<210>   41
<211>   114
<212>   PRT
<213>   Artificial Sequence

<220>
<223>   hRspondin3 furin domains

<400>   41
Met His Pro Asn Val Ser Gln Gly Cys Gln Gly Gly Cys Ala Thr Cys 
1               5                   10                  15      

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

Leu Glu Arg Ile Gly Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys 
        35                  40                  45              

Pro Ser Gly Tyr Tyr Gly Thr Arg Tyr Pro Asp Ile Asn Lys Cys Thr 
    50                  55                  60                  

Lys Cys Lys Ala Asp Cys Asp Thr Cys Phe Asn Lys Asn Phe Cys Thr 
65                  70                  75                  80  

Lys Cys Lys Ser Gly Phe Tyr Leu His Leu Gly Lys Cys Leu Asp Asn 
                85                  90                  95      

Cys Pro Glu Gly Leu Glu Ala Asn Asn His Thr Met Glu Cys Val Ser 
            100                 105                 110         

Ile Val 
        

