                         SEQUENCE LISTING

<110>  OncoMed Pharmaceuticals, Inc.
       Kapoun, Ann M.
       Zhang, Chun
       Wang, Min
       LIU, Yu-Wang
       O'YOUNG, Gilbert
       CATTARUZZA, Fiore
       
 
<120>  METHODS FOR TREATING CANCER USING RSPO3 ANTAGONISTS

<130>  2293.151PC02/PAC/MIG

<150>  62/308,577
<151>  2016-03-15

<150>  62/261,618
<151>  2015-12-01

<160>  55    

<170>  PatentIn version 3.5

<210>  1
<211>  263
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO1 amino acid sequence with signal sequence

<400>  1

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>  2
<211>  243
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO2 amino acid sequence with signal sequence

<400>  2

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 Pro 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>  3
<211>  272
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO3 amino acid sequence with signal sequence

<400>  3

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>  4
<211>  234
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO4 amino acid sequence with signal sequence

<400>  4

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

<220>
<223>  131R010 Heavy chain CDR1

<400>  5

Asp Tyr Ser Ile His 
1               5   


<210>  6
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Heavy chain CDR2

<400>  6

Tyr Ile Tyr Pro Ser Asn Gly Asp Ser Gly Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


<210>  7
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Heavy chain CDR3

<400>  7

Thr Tyr Phe Ala Asn Asn Phe Asp 
1               5               


<210>  8
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Alternative Heavy chain CDR3

<400>  8

Ala Thr Tyr Phe Ala Asn Asn Phe Asp Tyr 
1               5                   10  


<210>  9
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Light chain CDR1

<400>  9

Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn 
1               5                   10                  15  


<210>  10
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Light chain CDR2

<400>  10

Ala Ala Ser Asn Leu Glu Ser 
1               5           


<210>  11
<211>  3
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Alternative Light chain CDR2

<400>  11

Ala Ala Ser 
1           


<210>  12
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Light chain CDR3

<400>  12

Gln Gln Ser Asn Glu Asp Pro Leu Thr 
1               5                   


<210>  13
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010 Alternative Light chain CDR3

<400>  13

Gln Gln Ser Asn Glu Asp Pro Leu Thr Phe 
1               5                   10  


<210>  14
<211>  117
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010  Heavy chain variable region amino acid sequence

<400>  14

Gln 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 Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


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


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


Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Leu Thr Val Ser Ser 
        115         


<210>  15
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010  Light chain variable region

<400>  15

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


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


Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
        35                  40                  45              


Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
    50                  55                  60                  


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


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


Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg 
            100                 105                 110         


<210>  16
<211>  466
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010  Heavy chain


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  16

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


Val Leu Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe 
        35                  40                  45              


Thr Asp Tyr Ser Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Tyr Pro Ser Asn Gly Asp Ser Gly Tyr Asn 
65                  70                  75                  80  


Gln Lys Phe Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 
                85                  90                  95      


Thr Ala Tyr Met Glu Leu Ser Arg Leu Arg Ser Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Thr Tyr Phe Ala Asn Asn Phe Asp Tyr Trp Gly Gln 
        115                 120                 125             


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
145                 150                 155                 160 


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


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
            180                 185                 190         


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
        195                 200                 205             


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
    210                 215                 220                 


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp 
225                 230                 235                 240 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
                245                 250                 255     


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
            260                 265                 270         


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
        275                 280                 285             


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
    290                 295                 300                 


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
305                 310                 315                 320 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
                325                 330                 335     


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
            340                 345                 350         


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
        355                 360                 365             


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
    370                 375                 380                 


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
385                 390                 395                 400 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
                405                 410                 415     


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
            420                 425                 430         


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
        435                 440                 445             


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
    450                 455                 460                 


Gly Lys 
465     


<210>  17
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010  Heavy chain

<400>  17

Gln 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 Tyr Thr Phe Thr Asp Tyr 
            20                  25                  30          


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


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


Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Leu 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 Arg 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 Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


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


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


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


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


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


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


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


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


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


<210>  18
<211>  237
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010  Light chain


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  18

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


Val Leu Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
            20                  25                  30          


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


Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly 
    50                  55                  60                  


Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly 
65                  70                  75                  80  


Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 
                85                  90                  95      


Thr Ile Ser Pro Val Gln Ala Glu Asp Phe Ala Thr Tyr Tyr Cys Gln 
            100                 105                 110         


Gln Ser Asn Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu 
        115                 120                 125             


Leu Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser 
    130                 135                 140                 


Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn 
145                 150                 155                 160 


Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala 
                165                 170                 175     


Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys 
            180                 185                 190         


Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp 
        195                 200                 205             


Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu 
    210                 215                 220                 


Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 235         


<210>  19
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  131R010  Light chain

<400>  19

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


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


Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro 
        35                  40                  45              


Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Val Pro Ser 
    50                  55                  60                  


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


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


Glu Asp Pro Leu Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg 
            100                 105                 110         


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


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     


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


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


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             


<210>  20
<211>  951
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human LGR4 protein sequence

<400>  20

Met Pro Gly Pro Leu Gly Leu Leu Cys Phe Leu Ala Leu Gly Leu Leu 
1               5                   10                  15      


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


Cys Ser Cys Asp Gly Asp Arg Arg Val Asp Cys Ser Gly Lys Gly Leu 
        35                  40                  45              


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


Ser Met Asn Asn Ile Thr Gln Leu Pro Glu Asp Ala Phe Lys Asn Phe 
65                  70                  75                  80  


Pro Phe Leu Glu Glu Leu Gln Leu Ala Gly Asn Asp Leu Ser Phe Ile 
                85                  90                  95      


His Pro Lys Ala Leu Ser Gly Leu Lys Glu Leu Lys Val Leu Thr Leu 
            100                 105                 110         


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


Ser Ala Leu Gln Ser Leu Arg Leu Asp Ala Asn His Ile Thr Ser Val 
    130                 135                 140                 


Pro Glu Asp Ser Phe Glu Gly Leu Val Gln Leu Arg His Leu Trp Leu 
145                 150                 155                 160 


Asp Asp Asn Ser Leu Thr Glu Val Pro Val His Pro Leu Ser Asn Leu 
                165                 170                 175     


Pro Thr Leu Gln Ala Leu Thr Leu Ala Leu Asn Lys Ile Ser Ser Ile 
            180                 185                 190         


Pro Asp Phe Ala Phe Thr Asn Leu Ser Ser Leu Val Val Leu His Leu 
        195                 200                 205             


His Asn Asn Lys Ile Arg Ser Leu Ser Gln His Cys Phe Asp Gly Leu 
    210                 215                 220                 


Asp Asn Leu Glu Thr Leu Asp Leu Asn Tyr Asn Asn Leu Gly Glu Phe 
225                 230                 235                 240 


Pro Gln Ala Ile Lys Ala Leu Pro Ser Leu Lys Glu Leu Gly Phe His 
                245                 250                 255     


Ser Asn Ser Ile Ser Val Ile Pro Asp Gly Ala Phe Asp Gly Asn Pro 
            260                 265                 270         


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


Asn Ser Ala Phe His Asn Leu Ser Asp Leu His Ser Leu Val Ile Arg 
    290                 295                 300                 


Gly Ala Ser Met Val Gln Gln Phe Pro Asn Leu Thr Gly Thr Val His 
305                 310                 315                 320 


Leu Glu Ser Leu Thr Leu Thr Gly Thr Lys Ile Ser Ser Ile Pro Asn 
                325                 330                 335     


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


Asn Asn Ile Arg Asp Leu Pro Ser Phe Asn Gly Cys His Ala Leu Glu 
        355                 360                 365             


Glu Ile Ser Leu Gln Arg Asn Gln Ile Tyr Gln Ile Lys Glu Gly Thr 
    370                 375                 380                 


Phe Gln Gly Leu Ile Ser Leu Arg Ile Leu Asp Leu Ser Arg Asn Leu 
385                 390                 395                 400 


Ile His Glu Ile His Ser Arg Ala Phe Ala Thr Leu Gly Pro Ile Thr 
                405                 410                 415     


Asn Leu Asp Val Ser Phe Asn Glu Leu Thr Ser Phe Pro Thr Glu Gly 
            420                 425                 430         


Leu Asn Gly Leu Asn Gln Leu Lys Leu Val Gly Asn Phe Lys Leu Lys 
        435                 440                 445             


Glu Ala Leu Ala Ala Lys Asp Phe Val Asn Leu Arg Ser Leu Ser Val 
    450                 455                 460                 


Pro Tyr Ala Tyr Gln Cys Cys Ala Phe Trp Gly Cys Asp Ser Tyr Ala 
465                 470                 475                 480 


Asn Leu Asn Thr Glu Asp Asn Ser Leu Gln Asp His Ser Val Ala Gln 
                485                 490                 495     


Glu Lys Gly Thr Ala Asp Ala Ala Asn Val Thr Ser Thr Leu Glu Asn 
            500                 505                 510         


Glu Glu His Ser Gln Ile Ile Ile His Cys Thr Pro Ser Thr Gly Ala 
        515                 520                 525             


Phe Lys Pro Cys Glu Tyr Leu Leu Gly Ser Trp Met Ile Arg Leu Thr 
    530                 535                 540                 


Val Trp Phe Ile Phe Leu Val Ala Leu Phe Phe Asn Leu Leu Val Ile 
545                 550                 555                 560 


Leu Thr Thr Phe Ala Ser Cys Thr Ser Leu Pro Ser Ser Lys Leu Phe 
                565                 570                 575     


Ile Gly Leu Ile Ser Val Ser Asn Leu Phe Met Gly Ile Tyr Thr Gly 
            580                 585                 590         


Ile Leu Thr Phe Leu Asp Ala Val Ser Trp Gly Arg Phe Ala Glu Phe 
        595                 600                 605             


Gly Ile Trp Trp Glu Thr Gly Ser Gly Cys Lys Val Ala Gly Phe Leu 
    610                 615                 620                 


Ala Val Phe Ser Ser Glu Ser Ala Ile Phe Leu Leu Met Leu Ala Thr 
625                 630                 635                 640 


Val Glu Arg Ser Leu Ser Ala Lys Asp Ile Met Lys Asn Gly Lys Ser 
                645                 650                 655     


Asn His Leu Lys Gln Phe Arg Val Ala Ala Leu Leu Ala Phe Leu Gly 
            660                 665                 670         


Ala Thr Val Ala Gly Cys Phe Pro Leu Phe His Arg Gly Glu Tyr Ser 
        675                 680                 685             


Ala Ser Pro Leu Cys Leu Pro Phe Pro Thr Gly Glu Thr Pro Ser Leu 
    690                 695                 700                 


Gly Phe Thr Val Thr Leu Val Leu Leu Asn Ser Leu Ala Phe Leu Leu 
705                 710                 715                 720 


Met Ala Val Ile Tyr Thr Lys Leu Tyr Cys Asn Leu Glu Lys Glu Asp 
                725                 730                 735     


Leu Ser Glu Asn Ser Gln Ser Ser Met Ile Lys His Val Ala Trp Leu 
            740                 745                 750         


Ile Phe Thr Asn Cys Ile Phe Phe Cys Pro Val Ala Phe Phe Ser Phe 
        755                 760                 765             


Ala Pro Leu Ile Thr Ala Ile Ser Ile Ser Pro Glu Ile Met Lys Ser 
    770                 775                 780                 


Val Thr Leu Ile Phe Phe Pro Leu Pro Ala Cys Leu Asn Pro Val Leu 
785                 790                 795                 800 


Tyr Val Phe Phe Asn Pro Lys Phe Lys Glu Asp Trp Lys Leu Leu Lys 
                805                 810                 815     


Arg Arg Val Thr Lys Lys Ser Gly Ser Val Ser Val Ser Ile Ser Ser 
            820                 825                 830         


Gln Gly Gly Cys Leu Glu Gln Asp Phe Tyr Tyr Asp Cys Gly Met Tyr 
        835                 840                 845             


Ser His Leu Gln Gly Asn Leu Thr Val Cys Asp Cys Cys Glu Ser Phe 
    850                 855                 860                 


Leu Leu Thr Lys Pro Val Ser Cys Lys His Leu Ile Lys Ser His Ser 
865                 870                 875                 880 


Cys Pro Ala Leu Ala Val Ala Ser Cys Gln Arg Pro Glu Gly Tyr Trp 
                885                 890                 895     


Ser Asp Cys Gly Thr Gln Ser Ala His Ser Asp Tyr Ala Asp Glu Glu 
            900                 905                 910         


Asp Ser Phe Val Ser Asp Ser Ser Asp Gln Val Gln Ala Cys Gly Arg 
        915                 920                 925             


Ala Cys Phe Tyr Gln Ser Arg Gly Phe Pro Leu Val Arg Tyr Ala Tyr 
    930                 935                 940                 


Asn Leu Pro Arg Val Lys Asp 
945                 950     


<210>  21
<211>  907
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human LGR5 protein sequence

<400>  21

Met Asp Thr Ser Arg Leu Gly Val Leu Leu Ser Leu Pro Val Leu Leu 
1               5                   10                  15      


Gln Leu Ala Thr Gly Gly Ser Ser Pro Arg Ser Gly Val Leu Leu Arg 
            20                  25                  30          


Gly Cys Pro Thr His Cys His Cys Glu Pro Asp Gly Arg Met Leu Leu 
        35                  40                  45              


Arg Val Asp Cys Ser Asp Leu Gly Leu Ser Glu Leu Pro Ser Asn Leu 
    50                  55                  60                  


Ser Val Phe Thr Ser Tyr Leu Asp Leu Ser Met Asn Asn Ile Ser Gln 
65                  70                  75                  80  


Leu Leu Pro Asn Pro Leu Pro Ser Leu Arg Phe Leu Glu Glu Leu Arg 
                85                  90                  95      


Leu Ala Gly Asn Ala Leu Thr Tyr Ile Pro Lys Gly Ala Phe Thr Gly 
            100                 105                 110         


Leu Tyr Ser Leu Lys Val Leu Met Leu Gln Asn Asn Gln Leu Arg His 
        115                 120                 125             


Val Pro Thr Glu Ala Leu Gln Asn Leu Arg Ser Leu Gln Ser Leu Arg 
    130                 135                 140                 


Leu Asp Ala Asn His Ile Ser Tyr Val Pro Pro Ser Cys Phe Ser Gly 
145                 150                 155                 160 


Leu His Ser Leu Arg His Leu Trp Leu Asp Asp Asn Ala Leu Thr Glu 
                165                 170                 175     


Ile Pro Val Gln Ala Phe Arg Ser Leu Ser Ala Leu Gln Ala Met Thr 
            180                 185                 190         


Leu Ala Leu Asn Lys Ile His His Ile Pro Asp Tyr Ala Phe Gly Asn 
        195                 200                 205             


Leu Ser Ser Leu Val Val Leu His Leu His Asn Asn Arg Ile His Ser 
    210                 215                 220                 


Leu Gly Lys Lys Cys Phe Asp Gly Leu His Ser Leu Glu Thr Leu Asp 
225                 230                 235                 240 


Leu Asn Tyr Asn Asn Leu Asp Glu Phe Pro Thr Ala Ile Arg Thr Leu 
                245                 250                 255     


Ser Asn Leu Lys Glu Leu Gly Phe His Ser Asn Asn Ile Arg Ser Ile 
            260                 265                 270         


Pro Glu Lys Ala Phe Val Gly Asn Pro Ser Leu Ile Thr Ile His Phe 
        275                 280                 285             


Tyr Asp Asn Pro Ile Gln Phe Val Gly Arg Ser Ala Phe Gln His Leu 
    290                 295                 300                 


Pro Glu Leu Arg Thr Leu Thr Leu Asn Gly Ala Ser Gln Ile Thr Glu 
305                 310                 315                 320 


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


Gly Ala Gln Ile Ser Ser Leu Pro Gln Thr Val Cys Asn Gln Leu Pro 
            340                 345                 350         


Asn Leu Gln Val Leu Asp Leu Ser Tyr Asn Leu Leu Glu Asp Leu Pro 
        355                 360                 365             


Ser Phe Ser Val Cys Gln Lys Leu Gln Lys Ile Asp Leu Arg His Asn 
    370                 375                 380                 


Glu Ile Tyr Glu Ile Lys Val Asp Thr Phe Gln Gln Leu Leu Ser Leu 
385                 390                 395                 400 


Arg Ser Leu Asn Leu Ala Trp Asn Lys Ile Ala Ile Ile His Pro Asn 
                405                 410                 415     


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


Leu Leu Ser Ser Phe Pro Ile Thr Gly Leu His Gly Leu Thr His Leu 
        435                 440                 445             


Lys Leu Thr Gly Asn His Ala Leu Gln Ser Leu Ile Ser Ser Glu Asn 
    450                 455                 460                 


Phe Pro Glu Leu Lys Val Ile Glu Met Pro Tyr Ala Tyr Gln Cys Cys 
465                 470                 475                 480 


Ala Phe Gly Val Cys Glu Asn Ala Tyr Lys Ile Ser Asn Gln Trp Asn 
                485                 490                 495     


Lys Gly Asp Asn Ser Ser Met Asp Asp Leu His Lys Lys Asp Ala Gly 
            500                 505                 510         


Met Phe Gln Ala Gln Asp Glu Arg Asp Leu Glu Asp Phe Leu Leu Asp 
        515                 520                 525             


Phe Glu Glu Asp Leu Lys Ala Leu His Ser Val Gln Cys Ser Pro Ser 
    530                 535                 540                 


Pro Gly Pro Phe Lys Pro Cys Glu His Leu Leu Asp Gly Trp Leu Ile 
545                 550                 555                 560 


Arg Ile Gly Val Trp Thr Ile Ala Val Leu Ala Leu Thr Cys Asn Ala 
                565                 570                 575     


Leu Val Thr Ser Thr Val Phe Arg Ser Pro Leu Tyr Ile Ser Pro Ile 
            580                 585                 590         


Lys Leu Leu Ile Gly Val Ile Ala Ala Val Asn Met Leu Thr Gly Val 
        595                 600                 605             


Ser Ser Ala Val Leu Ala Gly Val Asp Ala Phe Thr Phe Gly Ser Phe 
    610                 615                 620                 


Ala Arg His Gly Ala Trp Trp Glu Asn Gly Val Gly Cys His Val Ile 
625                 630                 635                 640 


Gly Phe Leu Ser Ile Phe Ala Ser Glu Ser Ser Val Phe Leu Leu Thr 
                645                 650                 655     


Leu Ala Ala Leu Glu Arg Gly Phe Ser Val Lys Tyr Ser Ala Lys Phe 
            660                 665                 670         


Glu Thr Lys Ala Pro Phe Ser Ser Leu Lys Val Ile Ile Leu Leu Cys 
        675                 680                 685             


Ala Leu Leu Ala Leu Thr Met Ala Ala Val Pro Leu Leu Gly Gly Ser 
    690                 695                 700                 


Lys Tyr Gly Ala Ser Pro Leu Cys Leu Pro Leu Pro Phe Gly Glu Pro 
705                 710                 715                 720 


Ser Thr Met Gly Tyr Met Val Ala Leu Ile Leu Leu Asn Ser Leu Cys 
                725                 730                 735     


Phe Leu Met Met Thr Ile Ala Tyr Thr Lys Leu Tyr Cys Asn Leu Asp 
            740                 745                 750         


Lys Gly Asp Leu Glu Asn Ile Trp Asp Cys Ser Met Val Lys His Ile 
        755                 760                 765             


Ala Leu Leu Leu Phe Thr Asn Cys Ile Leu Asn Cys Pro Val Ala Phe 
    770                 775                 780                 


Leu Ser Phe Ser Ser Leu Ile Asn Leu Thr Phe Ile Ser Pro Glu Val 
785                 790                 795                 800 


Ile Lys Phe Ile Leu Leu Val Val Val Pro Leu Pro Ala Cys Leu Asn 
                805                 810                 815     


Pro Leu Leu Tyr Ile Leu Phe Asn Pro His Phe Lys Glu Asp Leu Val 
            820                 825                 830         


Ser Leu Arg Lys Gln Thr Tyr Val Trp Thr Arg Ser Lys His Pro Ser 
        835                 840                 845             


Leu Met Ser Ile Asn Ser Asp Asp Val Glu Lys Gln Ser Cys Asp Ser 
    850                 855                 860                 


Thr Gln Ala Leu Val Thr Phe Thr Ser Ser Ser Ile Thr Tyr Asp Leu 
865                 870                 875                 880 


Pro Pro Ser Ser Val Pro Ser Pro Ala Tyr Pro Val Thr Glu Ser Cys 
                885                 890                 895     


His Leu Ser Ser Val Ala Phe Val Pro Cys Leu 
            900                 905         


<210>  22
<211>  915
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human LGR6 protein sequence

<400>  22

Met Gly Arg Pro Arg Leu Thr Leu Val Cys Gln Val Ser Ile Ile Ile 
1               5                   10                  15      


Ser Ala Arg Asp Leu Ser Met Asn Asn Leu Thr Glu Leu Gln Pro Gly 
            20                  25                  30          


Leu Phe His His Leu Arg Phe Leu Glu Glu Leu Arg Leu Ser Gly Asn 
        35                  40                  45              


His Leu Ser His Ile Pro Gly Gln Ala Phe Ser Gly Leu Tyr Ser Leu 
    50                  55                  60                  


Lys Ile Leu Met Leu Gln Asn Asn Gln Leu Gly Gly Ile Pro Ala Glu 
65                  70                  75                  80  


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


Leu Ile Ser Leu Val Pro Glu Arg Ser Phe Glu Gly Leu Ser Ser Leu 
            100                 105                 110         


Arg His Leu Trp Leu Asp Asp Asn Ala Leu Thr Glu Ile Pro Val Arg 
        115                 120                 125             


Ala Leu Asn Asn Leu Pro Ala Leu Gln Ala Met Thr Leu Ala Leu Asn 
    130                 135                 140                 


Arg Ile Ser His Ile Pro Asp Tyr Ala Phe Gln Asn Leu Thr Ser Leu 
145                 150                 155                 160 


Val Val Leu His Leu His Asn Asn Arg Ile Gln His Leu Gly Thr His 
                165                 170                 175     


Ser Phe Glu Gly Leu His Asn Leu Glu Thr Leu Asp Leu Asn Tyr Asn 
            180                 185                 190         


Lys Leu Gln Glu Phe Pro Val Ala Ile Arg Thr Leu Gly Arg Leu Gln 
        195                 200                 205             


Glu Leu Gly Phe His Asn Asn Asn Ile Lys Ala Ile Pro Glu Lys Ala 
    210                 215                 220                 


Phe Met Gly Asn Pro Leu Leu Gln Thr Ile His Phe Tyr Asp Asn Pro 
225                 230                 235                 240 


Ile Gln Phe Val Gly Arg Ser Ala Phe Gln Tyr Leu Pro Lys Leu His 
                245                 250                 255     


Thr Leu Ser Leu Asn Gly Ala Met Asp Ile Gln Glu Phe Pro Asp Leu 
            260                 265                 270         


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


Arg Leu Leu Pro Ser Gly Met Cys Gln Gln Leu Pro Arg Leu Arg Val 
    290                 295                 300                 


Leu Glu Leu Ser His Asn Gln Ile Glu Glu Leu Pro Ser Leu His Arg 
305                 310                 315                 320 


Cys Gln Lys Leu Glu Glu Ile Gly Leu Gln His Asn Arg Ile Trp Glu 
                325                 330                 335     


Ile Gly Ala Asp Thr Phe Ser Gln Leu Ser Ser Leu Gln Ala Leu Asp 
            340                 345                 350         


Leu Ser Trp Asn Ala Ile Arg Ser Ile His Pro Glu Ala Phe Ser Thr 
        355                 360                 365             


Leu His Ser Leu Val Lys Leu Asp Leu Thr Asp Asn Gln Leu Thr Thr 
    370                 375                 380                 


Leu Pro Leu Ala Gly Leu Gly Gly Leu Met His Leu Lys Leu Lys Gly 
385                 390                 395                 400 


Asn Leu Ala Leu Ser Gln Ala Phe Ser Lys Asp Ser Phe Pro Lys Leu 
                405                 410                 415     


Arg Ile Leu Glu Val Pro Tyr Ala Tyr Gln Cys Cys Pro Tyr Gly Met 
            420                 425                 430         


Cys Ala Ser Phe Phe Lys Ala Ser Gly Gln Trp Glu Ala Glu Asp Leu 
        435                 440                 445             


His Leu Asp Asp Glu Glu Ser Ser Lys Arg Pro Leu Gly Leu Leu Ala 
    450                 455                 460                 


Arg Gln Ala Glu Asn His Tyr Asp Gln Asp Leu Asp Glu Leu Gln Leu 
465                 470                 475                 480 


Glu Met Glu Asp Ser Lys Pro His Pro Ser Val Gln Cys Ser Pro Thr 
                485                 490                 495     


Pro Gly Pro Phe Lys Pro Cys Glu Tyr Leu Phe Glu Ser Trp Gly Ile 
            500                 505                 510         


Arg Leu Ala Val Trp Ala Ile Val Leu Leu Ser Val Leu Cys Asn Gly 
        515                 520                 525             


Leu Val Leu Leu Thr Val Phe Ala Gly Gly Pro Val Pro Leu Pro Pro 
    530                 535                 540                 


Val Lys Phe Val Val Gly Ala Ile Ala Gly Ala Asn Thr Leu Thr Gly 
545                 550                 555                 560 


Ile Ser Cys Gly Leu Leu Ala Ser Val Asp Ala Leu Thr Phe Gly Gln 
                565                 570                 575     


Phe Ser Glu Tyr Gly Ala Arg Trp Glu Thr Gly Leu Gly Cys Arg Ala 
            580                 585                 590         


Thr Gly Phe Leu Ala Val Leu Gly Ser Glu Ala Ser Val Leu Leu Leu 
        595                 600                 605             


Thr Leu Ala Ala Val Gln Cys Ser Val Ser Val Ser Cys Val Arg Ala 
    610                 615                 620                 


Tyr Gly Lys Ser Pro Ser Leu Gly Ser Val Arg Ala Gly Val Leu Gly 
625                 630                 635                 640 


Cys Leu Ala Leu Ala Gly Leu Ala Ala Ala Leu Pro Leu Ala Ser Val 
                645                 650                 655     


Gly Glu Tyr Gly Ala Ser Pro Leu Cys Leu Pro Tyr Ala Pro Pro Glu 
            660                 665                 670         


Gly Gln Pro Ala Ala Leu Gly Phe Thr Val Ala Leu Val Met Met Asn 
        675                 680                 685             


Ser Phe Cys Phe Leu Val Val Ala Gly Ala Tyr Ile Lys Leu Tyr Cys 
    690                 695                 700                 


Asp Leu Pro Arg Gly Asp Phe Glu Ala Val Trp Asp Cys Ala Met Val 
705                 710                 715                 720 


Arg His Val Ala Trp Leu Ile Phe Ala Asp Gly Leu Leu Tyr Cys Pro 
                725                 730                 735     


Val Ala Phe Leu Ser Phe Ala Ser Met Leu Gly Leu Phe Pro Val Thr 
            740                 745                 750         


Pro Glu Ala Val Lys Ser Val Leu Leu Val Val Leu Pro Leu Pro Ala 
        755                 760                 765             


Cys Leu Asn Pro Leu Leu Tyr Leu Leu Phe Asn Pro His Phe Arg Asp 
    770                 775                 780                 


Asp Leu Arg Arg Leu Arg Pro Arg Ala Gly Asp Ser Gly Pro Leu Ala 
785                 790                 795                 800 


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


Ala Leu Val Ala Phe Ser Asp Val Asp Leu Ile Leu Glu Ala Ser Glu 
            820                 825                 830         


Ala Gly Arg Pro Pro Gly Leu Glu Thr Tyr Gly Phe Pro Ser Val Thr 
        835                 840                 845             


Leu Ile Ser Cys Gln Gln Pro Gly Ala Pro Arg Leu Glu Gly Ser His 
    850                 855                 860                 


Cys Val Glu Pro Glu Gly Asn His Phe Gly Asn Pro Gln Pro Ser Met 
865                 870                 875                 880 


Asp Gly Glu Leu Leu Leu Arg Ala Glu Gly Ser Thr Pro Ala Gly Gly 
                885                 890                 895     


Gly Leu Ser Gly Gly Gly Gly Phe Gln Pro Ser Gly Leu Ala Phe Ala 
            900                 905                 910         


Ser His Val 
        915 


<210>  23
<211>  543
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LGR5 ECD

<400>  23

Gly Ser Ser Pro Arg Ser Gly Val Leu Leu Arg Gly Cys Pro Thr His 
1               5                   10                  15      


Cys His Cys Glu Pro Asp Gly Arg Met Leu Leu Arg Val Asp Cys Ser 
            20                  25                  30          


Asp Leu Gly Leu Ser Glu Leu Pro Ser Asn Leu Ser Val Phe Thr Ser 
        35                  40                  45              


Tyr Leu Asp Leu Ser Met Asn Asn Ile Ser Gln Leu Leu Pro Asn Pro 
    50                  55                  60                  


Leu Pro Ser Leu Arg Phe Leu Glu Glu Leu Arg Leu Ala Gly Asn Ala 
65                  70                  75                  80  


Leu Thr Tyr Ile Pro Lys Gly Ala Phe Thr Gly Leu Tyr Ser Leu Lys 
                85                  90                  95      


Val Leu Met Leu Gln Asn Asn Gln Leu Arg His Val Pro Thr Glu Ala 
            100                 105                 110         


Leu Gln Asn Leu Arg Ser Leu Gln Ser Leu Arg Leu Asp Ala Asn His 
        115                 120                 125             


Ile Ser Tyr Val Pro Pro Ser Cys Phe Ser Gly Leu His Ser Leu Arg 
    130                 135                 140                 


His Leu Trp Leu Asp Asp Asn Ala Leu Thr Glu Ile Pro Val Gln Ala 
145                 150                 155                 160 


Phe Arg Ser Leu Ser Ala Leu Gln Ala Met Thr Leu Ala Leu Asn Lys 
                165                 170                 175     


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


Val Leu His Leu His Asn Asn Arg Ile His Ser Leu Gly Lys Lys Cys 
        195                 200                 205             


Phe Asp Gly Leu His Ser Leu Glu Thr Leu Asp Leu Asn Tyr Asn Asn 
    210                 215                 220                 


Leu Asp Glu Phe Pro Thr Ala Ile Arg Thr Leu Ser Asn Leu Lys Glu 
225                 230                 235                 240 


Leu Gly Phe His Ser Asn Asn Ile Arg Ser Ile Pro Glu Lys Ala Phe 
                245                 250                 255     


Val Gly Asn Pro Ser Leu Ile Thr Ile His Phe Tyr Asp Asn Pro Ile 
            260                 265                 270         


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


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


Gly Thr Ala Asn Leu Glu Ser Leu Thr Leu Thr Gly Ala Gln Ile Ser 
305                 310                 315                 320 


Ser Leu Pro Gln Thr Val Cys Asn Gln Leu Pro Asn Leu Gln Val Leu 
                325                 330                 335     


Asp Leu Ser Tyr Asn Leu Leu Glu Asp Leu Pro Ser Phe Ser Val Cys 
            340                 345                 350         


Gln Lys Leu Gln Lys Ile Asp Leu Arg His Asn Glu Ile Tyr Glu Ile 
        355                 360                 365             


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


Ala Trp Asn Lys Ile Ala Ile Ile His Pro Asn Ala Phe Ser Thr Leu 
385                 390                 395                 400 


Pro Ser Leu Ile Lys Leu Asp Leu Ser Ser Asn Leu Leu Ser Ser Phe 
                405                 410                 415     


Pro Ile Thr Gly Leu His Gly Leu Thr His Leu Lys Leu Thr Gly Asn 
            420                 425                 430         


His Ala Leu Gln Ser Leu Ile Ser Ser Glu Asn Phe Pro Glu Leu Lys 
        435                 440                 445             


Val Ile Glu Met Pro Tyr Ala Tyr Gln Cys Cys Ala Phe Gly Val Cys 
    450                 455                 460                 


Glu Asn Ala Tyr Lys Ile Ser Asn Gln Trp Asn Lys Gly Asp Asn Ser 
465                 470                 475                 480 


Ser Met Asp Asp Leu His Lys Lys Asp Ala Gly Met Phe Gln Ala Gln 
                485                 490                 495     


Asp Glu Arg Asp Leu Glu Asp Phe Leu Leu Asp Phe Glu Glu Asp Leu 
            500                 505                 510         


Lys Ala Leu His Ser Val Gln Cys Ser Pro Ser Pro Gly Pro Phe Lys 
        515                 520                 525             


Pro Cys Glu His Leu Leu Asp Gly Trp Leu Ile Arg Ile Gly Val 
    530                 535                 540             


<210>  24
<211>  794
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  LGR5-Fc

<400>  24

Met Asp Thr Ser Arg Leu Gly Val Leu Leu Ser Leu Pro Val Leu Leu 
1               5                   10                  15      


Gln Leu Ala Thr Gly Gly Ser Ser Pro Arg Ser Gly Val Leu Leu Arg 
            20                  25                  30          


Gly Cys Pro Thr His Cys His Cys Glu Pro Asp Gly Arg Met Leu Leu 
        35                  40                  45              


Arg Val Asp Cys Ser Asp Leu Gly Leu Ser Glu Leu Pro Ser Asn Leu 
    50                  55                  60                  


Ser Val Phe Thr Ser Tyr Leu Asp Leu Ser Met Asn Asn Ile Ser Gln 
65                  70                  75                  80  


Leu Leu Pro Asn Pro Leu Pro Ser Leu Arg Phe Leu Glu Glu Leu Arg 
                85                  90                  95      


Leu Ala Gly Asn Ala Leu Thr Tyr Ile Pro Lys Gly Ala Phe Thr Gly 
            100                 105                 110         


Leu Tyr Ser Leu Lys Val Leu Met Leu Gln Asn Asn Gln Leu Arg His 
        115                 120                 125             


Val Pro Thr Glu Ala Leu Gln Asn Leu Arg Ser Leu Gln Ser Leu Arg 
    130                 135                 140                 


Leu Asp Ala Asn His Ile Ser Tyr Val Pro Pro Ser Cys Phe Ser Gly 
145                 150                 155                 160 


Leu His Ser Leu Arg His Leu Trp Leu Asp Asp Asn Ala Leu Thr Glu 
                165                 170                 175     


Ile Pro Val Gln Ala Phe Arg Ser Leu Ser Ala Leu Gln Ala Met Thr 
            180                 185                 190         


Leu Ala Leu Asn Lys Ile His His Ile Pro Asp Tyr Ala Phe Gly Asn 
        195                 200                 205             


Leu Ser Ser Leu Val Val Leu His Leu His Asn Asn Arg Ile His Ser 
    210                 215                 220                 


Leu Gly Lys Lys Cys Phe Asp Gly Leu His Ser Leu Glu Thr Leu Asp 
225                 230                 235                 240 


Leu Asn Tyr Asn Asn Leu Asp Glu Phe Pro Thr Ala Ile Arg Thr Leu 
                245                 250                 255     


Ser Asn Leu Lys Glu Leu Gly Phe His Ser Asn Asn Ile Arg Ser Ile 
            260                 265                 270         


Pro Glu Lys Ala Phe Val Gly Asn Pro Ser Leu Ile Thr Ile His Phe 
        275                 280                 285             


Tyr Asp Asn Pro Ile Gln Phe Val Gly Arg Ser Ala Phe Gln His Leu 
    290                 295                 300                 


Pro Glu Leu Arg Thr Leu Thr Leu Asn Gly Ala Ser Gln Ile Thr Glu 
305                 310                 315                 320 


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


Gly Ala Gln Ile Ser Ser Leu Pro Gln Thr Val Cys Asn Gln Leu Pro 
            340                 345                 350         


Asn Leu Gln Val Leu Asp Leu Ser Tyr Asn Leu Leu Glu Asp Leu Pro 
        355                 360                 365             


Ser Phe Ser Val Cys Gln Lys Leu Gln Lys Ile Asp Leu Arg His Asn 
    370                 375                 380                 


Glu Ile Tyr Glu Ile Lys Val Asp Thr Phe Gln Gln Leu Leu Ser Leu 
385                 390                 395                 400 


Arg Ser Leu Asn Leu Ala Trp Asn Lys Ile Ala Ile Ile His Pro Asn 
                405                 410                 415     


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


Leu Leu Ser Ser Phe Pro Ile Thr Gly Leu His Gly Leu Thr His Leu 
        435                 440                 445             


Lys Leu Thr Gly Asn His Ala Leu Gln Ser Leu Ile Ser Ser Glu Asn 
    450                 455                 460                 


Phe Pro Glu Leu Lys Val Ile Glu Met Pro Tyr Ala Tyr Gln Cys Cys 
465                 470                 475                 480 


Ala Phe Gly Val Cys Glu Asn Ala Tyr Lys Ile Ser Asn Gln Trp Asn 
                485                 490                 495     


Lys Gly Asp Asn Ser Ser Met Asp Asp Leu His Lys Lys Asp Ala Gly 
            500                 505                 510         


Met Phe Gln Ala Gln Asp Glu Arg Asp Leu Glu Asp Phe Leu Leu Asp 
        515                 520                 525             


Phe Glu Glu Asp Leu Lys Ala Leu His Ser Val Gln Cys Ser Pro Ser 
    530                 535                 540                 


Pro Gly Pro Phe Lys Pro Cys Glu His Leu Leu Asp Gly Trp Leu Ile 
545                 550                 555                 560 


Arg Ile Gly Val Gly Arg Ala Asp Lys Thr His Thr Cys Pro Pro Cys 
                565                 570                 575     


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
            580                 585                 590         


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
        595                 600                 605             


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
    610                 615                 620                 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
625                 630                 635                 640 


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
                645                 650                 655     


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
            660                 665                 670         


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
        675                 680                 685             


Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu 
    690                 695                 700                 


Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
705                 710                 715                 720 


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
                725                 730                 735     


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
            740                 745                 750         


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
        755                 760                 765             


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
    770                 775                 780                 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
785                 790                 


<210>  25
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG1 Fc region

<400>  25

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>  26
<211>  227
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG1 Fc region

<400>  26

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 Glu Glu Met 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>  27
<211>  230
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG1 Fc region

<400>  27

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Leu Ser Pro Gly Lys 
225                 230 


<210>  28
<211>  232
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG1 Fc region

<400>  28

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


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
            20                  25                  30          


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
        35                  40                  45              


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


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
65                  70                  75                  80  


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                85                  90                  95      


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
            100                 105                 110         


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                165                 170                 175     


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


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
        195                 200                 205             


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


Ser Leu Ser Leu Ser Pro Gly Lys 
225                 230         


<210>  29
<211>  224
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG2 Fc region

<400>  29

Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser 
1               5                   10                  15      


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


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


Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
    50                  55                  60                  


Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val 
65                  70                  75                  80  


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


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


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


Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
    130                 135                 140                 


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


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp 
                165                 170                 175     


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


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
        195                 200                 205             


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    210                 215                 220                 


<210>  30
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_1P

<400>  30
tgcacagcct ccttggcagc ct                                                22


<210>  31
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_1FW

<400>  31
gcgaagaatg catcctaacg tt                                                22


<210>  32
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3 1REV

<400>  32
gggcttacat gacaaacatc ca                                                22


<210>  33
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_2P

<400>  33
aagtagtctc cagctctatg atttcttcca catttgtct                              39


<210>  34
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_2FW

<400>  34
agaaacacaa gagtgcatac cagaa                                             25


<210>  35
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_2REV

<400>  35
tgaccacaat ccttcacagt tttg                                              24


<210>  36
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_3P

<400>  36
tgcacagcct ccttggcagc cttgact                                           27


<210>  37
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_3FW

<400>  37
ccagcgaaga atgcatccta acg                                               23


<210>  38
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_3REV

<400>  38
gtctgggctt acatgacaaa catcc                                             25


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

<220>
<223>  RSPO3_4P

<400>  39
tcttcgtgca tggactccaa ggattcc                                           27


<210>  40
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_4FW

<400>  40
gtcagtattg tgcactgtga gg                                                22


<210>  41
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_4REV

<400>  41
ccgtgtttca gtccctcttt tg                                                22


<210>  42
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_5P

<400>  42
tggcttccaa cccttctgg                                                    19


<210>  43
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_5FW

<400>  43
acaccttgga aagtgccttg ac                                                22


<210>  44
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_5REV

<400>  44
tgcacaatac tgacacactc catag                                             25


<210>  45
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_6P

<400>  45
tcttttcctc tcccttcct                                                    19


<210>  46
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_6FW

<400>  46
gtgcaaagga agaagtgtca ga                                                22


<210>  47
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_6REV

<400>  47
caggtattgc ttctttactt tctcc                                             25


<210>  48
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_8P

<400>  48
tgtggctcag cctctgttac cccttgg                                           27


<210>  49
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_8FW

<400>  49
acaggtctcc aatctatgtt agcac                                             25


<210>  50
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_8REV

<400>  50
acaggcacat gtttacaggt tgata                                             25


<210>  51
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_9P

<400>  51
tttcctctcc cttccttt                                                     18


<210>  52
<211>  19
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_9FW

<400>  52
ggaagaagtg tcagaaggg                                                    19


<210>  53
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3_9REV

<400>  53
gcttctttac tttctccttt attag                                             25


<210>  54
<211>  4583
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  RSPO3 NM_032784.4

<400>  54
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>  55
<211>  43
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PTPRK exon 13-RSPO3 exon2 junction

<400>  55
gtgcgtacgc attgctacaa aagtgcatcc taacgttagt caa                         43


