                         SEQUENCE LISTING

<110>  ROYAL COLLEGE OF SURGEONS IN IRELAND
 
<120>  ADAM22 FOR USE AS A PROGNOSTIC VARIABLE, AND TARGET FOR THERAPY, 
       OF A METASTATIC BREAST CANCER DISEASE

<130>  P10757PC00

<150>  EP11187962.3
<151>  2011-11-04

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  557
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(557)
<223>  LGI1 protein

<400>  1

Met Glu Ser Glu Arg Ser Lys Arg Met Gly Asn Ala Cys Ile Pro Leu 
1               5                   10                  15      


Lys Arg Ile Ala Tyr Phe Leu Cys Leu Leu Ser Ala Leu Leu Leu Thr 
            20                  25                  30          


Glu Gly Lys Lys Pro Ala Lys Pro Lys Cys Pro Ala Val Cys Thr Cys 
        35                  40                  45              


Thr Lys Asp Asn Ala Leu Cys Glu Asn Ala Arg Ser Ile Pro Arg Thr 
    50                  55                  60                  


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


Glu Ile Ser Glu Gly Ser Phe Leu Phe Thr Pro Ser Leu Gln Leu Leu 
                85                  90                  95      


Leu Phe Thr Ser Asn Ser Phe Asp Val Ile Ser Asp Asp Ala Phe Ile 
            100                 105                 110         


Gly Leu Pro His Leu Glu Tyr Leu Phe Ile Glu Asn Asn Asn Ile Lys 
        115                 120                 125             


Ser Ile Ser Arg His Thr Phe Arg Gly Leu Lys Ser Leu Ile His Leu 
    130                 135                 140                 


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


Gly Leu Asp Ser Leu Thr Asn Val Asp Leu Arg Gly Asn Ser Phe Asn 
                165                 170                 175     


Cys Asp Cys Lys Leu Lys Trp Leu Val Glu Trp Leu Gly His Thr Asn 
            180                 185                 190         


Ala Thr Val Glu Asp Ile Tyr Cys Glu Gly Pro Pro Glu Tyr Lys Lys 
        195                 200                 205             


Arg Lys Ile Asn Ser Leu Ser Ser Lys Asp Phe Asp Cys Ile Ile Thr 
    210                 215                 220                 


Glu Phe Ala Lys Ser Gln Asp Leu Pro Tyr Gln Ser Leu Ser Ile Asp 
225                 230                 235                 240 


Thr Phe Ser Tyr Leu Asn Asp Glu Tyr Val Val Ile Ala Gln Pro Phe 
                245                 250                 255     


Thr Gly Lys Cys Ile Phe Leu Glu Trp Asp His Val Glu Lys Thr Phe 
            260                 265                 270         


Arg Asn Tyr Asp Asn Ile Thr Gly Thr Ser Thr Val Val Cys Lys Pro 
        275                 280                 285             


Ile Val Ile Glu Thr Gln Leu Tyr Val Ile Val Ala Gln Leu Phe Gly 
    290                 295                 300                 


Gly Ser His Ile Tyr Lys Arg Asp Ser Phe Ala Asn Lys Phe Ile Lys 
305                 310                 315                 320 


Ile Gln Asp Ile Glu Ile Leu Lys Ile Arg Lys Pro Asn Asp Ile Glu 
                325                 330                 335     


Thr Phe Lys Ile Glu Asn Asn Trp Tyr Phe Val Val Ala Asp Ser Ser 
            340                 345                 350         


Lys Ala Gly Phe Thr Thr Ile Tyr Lys Trp Asn Gly Asn Gly Phe Tyr 
        355                 360                 365             


Ser His Gln Ser Leu His Ala Trp Tyr Arg Asp Thr Asp Val Glu Tyr 
    370                 375                 380                 


Leu Glu Ile Val Arg Thr Pro Gln Thr Leu Arg Thr Pro His Leu Ile 
385                 390                 395                 400 


Leu Ser Ser Ser Ser Gln Arg Pro Val Ile Tyr Gln Trp Asn Lys Ala 
                405                 410                 415     


Thr Gln Leu Phe Thr Asn Gln Thr Asp Ile Pro Asn Met Glu Asp Val 
            420                 425                 430         


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


Thr Arg Phe Ile Gly Asp Ser Lys Val Met Lys Trp Gly Gly Ser Ser 
    450                 455                 460                 


Phe Gln Asp Ile Gln Arg Met Pro Ser Arg Gly Ser Met Val Phe Gln 
465                 470                 475                 480 


Pro Leu Gln Ile Asn Asn Tyr Gln Tyr Ala Ile Leu Gly Ser Asp Tyr 
                485                 490                 495     


Ser Phe Thr Gln Val Tyr Asn Trp Asp Ala Glu Lys Ala Lys Phe Val 
            500                 505                 510         


Lys Phe Gln Glu Leu Asn Val Gln Ala Pro Arg Ser Phe Thr His Val 
        515                 520                 525             


Ser Ile Asn Lys Arg Asn Phe Leu Phe Ala Ser Ser Phe Lys Gly Asn 
    530                 535                 540                 


Thr Gln Ile Tyr Lys His Val Ile Val Asp Leu Ser Ala 
545                 550                 555         


<210>  2
<211>  859
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(342)
<223>  ADAM22 protein

<400>  2

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


Leu Gly Thr Cys Pro Pro Ala Arg Cys Gly Gln Ala Gly Asp Ala Ser 
            20                  25                  30          


Leu Met Glu Leu Glu Lys Arg Lys Glu Asn Arg Phe Val Glu Arg Gln 
        35                  40                  45              


Ser Ile Val Pro Leu Arg Leu Ile Tyr Arg Ser Gly Gly Glu Asp Glu 
    50                  55                  60                  


Ser Arg His Asp Ala Leu Asp Thr Arg Val Arg Gly Asp Leu Gly Gly 
65                  70                  75                  80  


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


Gly Thr Ser Phe Ile Leu Asp Val Val Leu Asn His Asp Leu Leu Ser 
            100                 105                 110         


Ser Glu Tyr Ile Glu Arg His Ile Glu His Gly Gly Lys Thr Val Glu 
        115                 120                 125             


Val Lys Gly Gly Glu His Cys Tyr Tyr Gln Gly His Ile Arg Gly Asn 
    130                 135                 140                 


Pro Asp Ser Phe Val Ala Leu Ser Thr Cys His Gly Leu His Gly Met 
145                 150                 155                 160 


Phe Tyr Asp Gly Asn His Thr Tyr Leu Ile Glu Pro Glu Glu Asn Asp 
                165                 170                 175     


Thr Thr Gln Glu Asp Phe His Phe His Ser Val Tyr Lys Ser Arg Leu 
            180                 185                 190         


Phe Glu Phe Ser Leu Asp Asp Leu Pro Ser Glu Phe Gln Gln Val Asn 
        195                 200                 205             


Ile Thr Pro Ser Lys Phe Ile Leu Lys Pro Arg Pro Lys Arg Ser Lys 
    210                 215                 220                 


Arg Gln Leu Arg Arg Tyr Pro Arg Asn Val Glu Glu Glu Thr Lys Tyr 
225                 230                 235                 240 


Ile Glu Leu Met Ile Val Asn Asp His Leu Met Phe Lys Lys His Arg 
                245                 250                 255     


Leu Ser Val Val His Thr Asn Thr Tyr Ala Lys Ser Val Val Asn Met 
            260                 265                 270         


Ala Asp Leu Ile Tyr Lys Asp Gln Leu Lys Thr Arg Ile Val Leu Val 
        275                 280                 285             


Ala Met Glu Thr Trp Ala Thr Asp Asn Lys Phe Ala Ile Ser Glu Asn 
    290                 295                 300                 


Pro Leu Ile Thr Leu Arg Glu Phe Met Lys Tyr Arg Arg Asp Phe Ile 
305                 310                 315                 320 


Lys Glu Lys Ser Asp Ala Val His Leu Phe Ser Gly Ser Gln Phe Glu 
                325                 330                 335     


Ser Ser Arg Ser Gly Ala Ala Tyr Ile Gly Gly Ile Cys Ser Leu Leu 
            340                 345                 350         


Lys Gly Gly Gly Val Asn Glu Phe Gly Lys Thr Asp Leu Met Ala Val 
        355                 360                 365             


Thr Leu Ala Gln Ser Leu Ala His Asn Ile Gly Ile Ile Ser Asp Lys 
    370                 375                 380                 


Arg Lys Leu Ala Ser Gly Glu Cys Lys Cys Glu Asp Thr Trp Ser Gly 
385                 390                 395                 400 


Cys Ile Met Gly Asp Thr Gly Tyr Tyr Leu Pro Lys Lys Phe Thr Gln 
                405                 410                 415     


Cys Asn Ile Glu Glu Tyr His Asp Phe Leu Asn Ser Gly Gly Gly Ala 
            420                 425                 430         


Cys Leu Phe Asn Lys Pro Ser Lys Leu Leu Asp Pro Pro Glu Cys Gly 
        435                 440                 445             


Asn Gly Phe Ile Glu Thr Gly Glu Glu Cys Asp Cys Gly Thr Pro Ala 
    450                 455                 460                 


Glu Cys Val Leu Glu Gly Ala Glu Cys Cys Lys Lys Cys Thr Leu Thr 
465                 470                 475                 480 


Gln Asp Ser Gln Cys Ser Asp Gly Leu Cys Cys Lys Lys Cys Lys Phe 
                485                 490                 495     


Gln Pro Met Gly Thr Val Cys Arg Glu Ala Val Asn Asp Cys Asp Ile 
            500                 505                 510         


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


Lys Met Asp Gly Tyr Ser Cys Asp Gly Val Gln Gly Ile Cys Phe Gly 
    530                 535                 540                 


Gly Arg Cys Lys Thr Arg Asp Arg Gln Cys Lys Tyr Ile Trp Gly Gln 
545                 550                 555                 560 


Lys Val Thr Ala Ser Asp Lys Tyr Cys Tyr Glu Lys Leu Asn Ile Glu 
                565                 570                 575     


Gly Thr Glu Lys Gly Asn Cys Gly Lys Asp Lys Asp Thr Trp Ile Gln 
            580                 585                 590         


Cys Asn Lys Arg Asp Val Leu Cys Gly Tyr Leu Leu Cys Thr Asn Ile 
        595                 600                 605             


Gly Asn Ile Pro Arg Leu Gly Glu Leu Asp Gly Glu Ile Thr Ser Thr 
    610                 615                 620                 


Leu Val Val Gln Gln Gly Arg Thr Leu Asn Cys Ser Gly Gly His Val 
625                 630                 635                 640 


Lys Leu Glu Glu Asp Val Asp Leu Gly Tyr Val Glu Asp Gly Thr Pro 
                645                 650                 655     


Cys Gly Pro Gln Met Met Cys Leu Glu His Arg Cys Leu Pro Val Ala 
            660                 665                 670         


Ser Phe Asn Phe Ser Thr Cys Leu Ser Ser Lys Glu Gly Thr Ile Cys 
        675                 680                 685             


Ser Gly Asn Gly Val Cys Ser Asn Glu Leu Lys Cys Val Cys Asn Arg 
    690                 695                 700                 


His Trp Ile Gly Ser Asp Cys Asn Thr Tyr Phe Pro His Asn Asp Asp 
705                 710                 715                 720 


Ala Lys Thr Gly Ile Thr Leu Ser Gly Asn Gly Val Ala Gly Thr Asn 
                725                 730                 735     


Ile Ile Ile Gly Ile Ile Ala Gly Thr Ile Leu Val Leu Ala Leu Ile 
            740                 745                 750         


Leu Gly Ile Thr Ala Trp Gly Tyr Lys Asn Tyr Arg Glu Gln Arg Gln 
        755                 760                 765             


Leu Pro Gln Gly Asp Tyr Val Lys Lys Pro Gly Asp Gly Asp Ser Phe 
    770                 775                 780                 


Tyr Ser Asp Ile Pro Pro Gly Val Ser Thr Asn Ser Ala Ser Ser Ser 
785                 790                 795                 800 


Lys Lys Arg Ser Asn Gly Leu Ser His Ser Trp Ser Glu Arg Ile Pro 
                805                 810                 815     


Asp Thr Lys His Ile Ser Asp Ile Cys Glu Asn Gly Arg Pro Arg Ser 
            820                 825                 830         


Asn Ser Trp Gln Gly Asn Leu Gly Gly Asn Lys Lys Lys Ile Arg Gly 
        835                 840                 845             


Lys Arg Phe Arg Pro Arg Ser Asn Ser Thr Glu 
    850                 855                 


<210>  3
<211>  34
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(34)
<223>  ADAM22 binding domain of LGI1

<400>  3

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


Val Met Lys Trp Gly Gly Ser Ser Phe Gln Asp Ile Gln Arg Met Pro 
            20                  25                  30          


Ser Arg 
        


<210>  4
<211>  34
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(34)
<223>  LGI1 binding domain of ADAM22

<400>  4

Cys Arg Glu Ala Val Asn Asp Cys Asp Ile Arg Glu Thr Cys Ser Gly 
1               5                   10                  15      


Asn Ser Ser Gln Cys Ala Pro Asn Ile His Lys Met Asp Gly Tyr Ser 
            20                  25                  30          


Cys Asp 
        


<210>  5
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  5

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


Val Met Lys Trp Gly Gly 
            20          


<210>  6
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  6

Lys Gly Asp Val Tyr Ile Ser Leu Thr Arg Phe Ile Gly Asp Ser Lys 
1               5                   10                  15      


Val Met Lys Trp Gly Gly 
            20          


<210>  7
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  7

Asp Val Tyr Ile Cys Leu Thr Arg Phe Ile Gly Asp Ser Lys Val Met 
1               5                   10                  15      


Lys Trp Gly Gly Ser Ser 
            20          


<210>  8
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  8

Tyr Ile Cys Leu Thr Arg Phe Ile Gly Asp Ser Lys Val Met Lys Trp 
1               5                   10                  15      


Gly Gly Ser Ser Phe Gln 
            20          


<210>  9
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  9

Cys Leu Thr Arg Phe Ile Gly Asp Ser Lys Val Met Lys Trp Gly Gly 
1               5                   10                  15      


Ser Ser Phe Gln Asp Ile 
            20          


<210>  10
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  10

Thr Arg Phe Ile Gly Asp Ser Lys Val Met Lys Trp Gly Gly Ser Ser 
1               5                   10                  15      


Phe Gln Asp Ile Gln Arg 
            20          


<210>  11
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  11

Phe Ile Gly Asp Ser Lys Val Met Lys Trp Gly Gly Ser Ser Phe Gln 
1               5                   10                  15      


Asp Ile Gln Arg Met Pro 
            20          


<210>  12
<211>  22
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (1)..(22)
<223>  Fragment of ADAM22 binding domain of LGI1

<400>  12

Gly Asp Ser Lys Val Met Lys Trp Gly Gly Ser Ser Phe Gln Asp Ile 
1               5                   10                  15      


Gln Arg Met Pro Ser Arg 
            20          


