                         SEQUENCE LISTING

<110>  The Governing Council of the University of Toronto
 
<120>  KRAB FUSION REPRESSORS AND METHODS AND COMPOSITIONS FOR 
       REPRESSING GENE EXPRESSION

<130>  2223-P61944PC00

<150>  US 63/065,953
<151>  2020-08-14

<160>  18    

<170>  PatentIn version 3.5

<210>  1
<211>  1368
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  1

Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


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


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


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


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


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


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


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


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp Ala Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


<210>  2
<211>  62
<212>  PRT
<213>  Homo sapiens

<400>  2

Val Thr Phe Glu Asp Val Thr Val Asn Phe Thr Gln Gly Glu Trp Gln 
1               5                   10                  15      


Arg Leu Asn Pro Glu Gln Arg Asn Leu Tyr Arg Asp Val Met Leu Glu 
            20                  25                  30          


Asn Tyr Ser Asn Leu Val Ser Val Gly Gln Gly Glu Thr Thr Lys Pro 
        35                  40                  45              


Asp Val Ile Leu Arg Leu Glu Gln Gly Lys Glu Pro Trp Leu 
    50                  55                  60          


<210>  3
<211>  100
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Asn Asn Ser Gln Gly Arg Val Thr Phe Glu Asp Val Thr Val Asn 
1               5                   10                  15      


Phe Thr Gln Gly Glu Trp Gln Arg Leu Asn Pro Glu Gln Arg Asn Leu 
            20                  25                  30          


Tyr Arg Asp Val Met Leu Glu Asn Tyr Ser Asn Leu Val Ser Val Gly 
        35                  40                  45              


Gln Gly Glu Thr Thr Lys Pro Asp Val Ile Leu Arg Leu Glu Gln Gly 
    50                  55                  60                  


Lys Glu Pro Trp Leu Glu Glu Glu Glu Val Leu Gly Ser Gly Arg Ala 
65                  70                  75                  80  


Glu Lys Asn Gly Asp Ile Gly Gly Gln Ile Trp Lys Pro Lys Asp Val 
                85                  90                  95      


Lys Glu Ser Leu 
            100 


<210>  4
<211>  144
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Phe Ser Gln Glu Glu Arg Met Ala Ala Gly Tyr Leu Pro Arg Trp 
1               5                   10                  15      


Ser Gln Glu Leu Val Thr Phe Glu Asp Val Ser Met Asp Phe Ser Gln 
            20                  25                  30          


Glu Glu Trp Glu Leu Leu Glu Pro Ala Gln Lys Asn Leu Tyr Arg Glu 
        35                  40                  45              


Val Met Leu Glu Asn Tyr Arg Asn Val Val Ser Leu Glu Ala Leu Lys 
    50                  55                  60                  


Asn Gln Cys Thr Asp Val Gly Ile Lys Glu Gly Pro Leu Ser Pro Ala 
65                  70                  75                  80  


Gln Thr Ser Gln Val Thr Ser Leu Ser Ser Trp Thr Gly Tyr Leu Leu 
                85                  90                  95      


Phe Gln Pro Val Ala Ser Ser His Leu Glu Gln Arg Glu Ala Leu Trp 
            100                 105                 110         


Ile Glu Glu Lys Gly Thr Pro Gln Ala Ser Cys Ser Asp Trp Met Thr 
        115                 120                 125             


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


<210>  5
<211>  105
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Ala Ala Ala Val Leu Thr Asp Arg Ala Gln Val Ser Val Thr Phe 
1               5                   10                  15      


Asp Asp Val Ala Val Thr Phe Thr Lys Glu Glu Trp Gly Gln Leu Asp 
            20                  25                  30          


Leu Ala Gln Arg Thr Leu Tyr Gln Glu Val Met Leu Glu Asn Cys Gly 
        35                  40                  45              


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


His Leu Glu His Gly Gln Glu Pro Trp Thr Arg Lys Glu Asp Leu Ser 
65                  70                  75                  80  


Gln Asp Thr Cys Pro Gly Asp Lys Gly Lys Pro Lys Thr Thr Glu Pro 
                85                  90                  95      


Thr Thr Cys Glu Pro Ala Leu Ser Glu 
            100                 105 


<210>  6
<211>  92
<212>  PRT
<213>  Homo sapiens

<400>  6

Met Ala Phe Glu Asp Val Ala Val Tyr Phe Ser Gln Glu Glu Trp Gly 
1               5                   10                  15      


Leu Leu Asp Thr Ala Gln Arg Ala Leu Tyr Arg Arg Val Met Leu Asp 
            20                  25                  30          


Asn Phe Ala Leu Val Ala Ser Leu Gly Leu Ser Thr Ser Arg Pro Arg 
        35                  40                  45              


Val Val Ile Gln Leu Glu Arg Gly Glu Glu Pro Trp Val Pro Ser Gly 
    50                  55                  60                  


Thr Asp Thr Thr Leu Ser Arg Thr Thr Tyr Arg Arg Arg Asn Pro Gly 
65                  70                  75                  80  


Ser Trp Ser Leu Thr Glu Asp Arg Asp Val Ser Gly 
                85                  90          


<210>  7
<211>  127
<212>  PRT
<213>  Homo sapiens

<400>  7

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


Ile Gln Asp Ser Val Ala Phe Glu Asp Val Ala Val Asn Phe Thr Gln 
            20                  25                  30          


Glu Glu Trp Ala Leu Leu Asp Ser Ser Gln Lys Asn Leu Tyr Arg Glu 
        35                  40                  45              


Val Met Gln Glu Thr Cys Arg Asn Leu Ala Ser Val Gly Ser Gln Trp 
    50                  55                  60                  


Lys Asp Gln Asn Ile Glu Asp His Phe Glu Lys Pro Gly Lys Asp Ile 
65                  70                  75                  80  


Arg Asn His Ile Val Gln Arg Leu Cys Glu Ser Lys Glu Asp Gly Gln 
                85                  90                  95      


Tyr Gly Glu Val Val Ser Gln Ile Pro Asn Leu Asp Leu Asn Glu Asn 
            100                 105                 110         


Ile Ser Thr Gly Leu Lys Pro Cys Glu Cys Ser Ile Cys Gly Lys 
        115                 120                 125         


<210>  8
<211>  105
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Ala Ala Gly Gln Arg Glu Ala Arg Pro Gln Val Ser Leu Thr Phe 
1               5                   10                  15      


Glu Asp Val Ala Val Leu Phe Thr Arg Asp Glu Trp Arg Lys Leu Ala 
            20                  25                  30          


Pro Ser Gln Arg Asn Leu Tyr Arg Asp Val Met Leu Glu Asn Tyr Arg 
        35                  40                  45              


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


Leu Leu Gln Gln Gly Glu Asp Pro Trp Glu Val Glu Lys Asp Gly Ser 
65                  70                  75                  80  


Gly Val Ser Ser Leu Gly Ser Lys Ser Ser His Lys Thr Thr Lys Ser 
                85                  90                  95      


Thr Gln Thr Gln Asp Ser Ser Phe Gln 
            100                 105 


<210>  9
<211>  97
<212>  PRT
<213>  Homo sapiens

<400>  9

Met Ala Leu Arg Ser Val Met Phe Ser Asp Val Ser Ile Asp Phe Ser 
1               5                   10                  15      


Pro Glu Glu Trp Glu Tyr Leu Asp Leu Glu Gln Lys Asp Leu Tyr Arg 
            20                  25                  30          


Asp Val Met Leu Glu Asn Tyr Ser Asn Leu Val Ser Leu Gly Cys Phe 
        35                  40                  45              


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


Trp Lys Val Val Arg Lys Gly Arg Arg Gln Tyr Pro Asp Leu Glu Thr 
65                  70                  75                  80  


Lys Tyr Glu Thr Lys Lys Leu Ser Leu Glu Asn Asp Ile Tyr Glu Ile 
                85                  90                  95      


Asn 
    


<210>  10
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  10

Met Ala Gln Glu Ser Val Met Phe Ser Asp Val Ser Val Asp Phe Ser 
1               5                   10                  15      


Gln Glu Glu Trp Glu Cys Leu Asn Asp Asp Gln Arg Asp Leu Tyr Arg 
            20                  25                  30          


Asp Val Met Leu Glu Asn Tyr Ser Asn Leu Val Ser Met Gly His Ser 
        35                  40                  45              


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


Trp Leu Ala Asp Arg Glu Leu Thr Arg Gly Gln Trp Pro Val Leu Glu 
65                  70                  75                  80  


Ser Arg Cys Glu Thr Lys Lys Leu Phe Leu Lys Lys Glu Ile Tyr Glu 
                85                  90                  95      


Ile Glu Ser Thr Gln Trp Glu Ile Met Glu Lys 
            100                 105         


<210>  11
<211>  86
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  11
gtttcagagc tatgctggaa acagcatagc aagttgaaat aaggctagtc cgttatcaac       60

ttgaaaaagt ggcaccgagt cggtgc                                            86


<210>  12
<211>  76
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  12
gttttagagc tagaaatagc aagttaaaat aaggctagtc cgttatcaac ttgaaaaagt       60

ggcaccgagt cggtgc                                                       76


<210>  13
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  13
gtttcagagc tacagcagaa atgctgtagc aagttgaaat                             40


<210>  14
<211>  1550
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (1)..(8)
<223>  Flanking

<220>
<221>  MISC_FEATURE
<222>  (9)..(108)
<223>  ZIM3-KRAB

<220>
<221>  MISC_FEATURE
<222>  (109)..(117)
<223>  Flanking

<220>
<221>  MISC_FEATURE
<222>  (149)..(1516)
<223>  dCas9

<220>
<221>  MISC_FEATURE
<222>  (1518)..(1526)
<223>  HA

<220>
<221>  MISC_FEATURE
<222>  (1533)..(1539)
<223>  NLS

<220>
<221>  MISC_FEATURE
<222>  (1542)..(1548)
<223>  NLS

<400>  14

Thr Ser Leu Tyr Lys Lys Val Gly Met Asn Asn Ser Gln Gly Arg Val 
1               5                   10                  15      


Thr Phe Glu Asp Val Thr Val Asn Phe Thr Gln Gly Glu Trp Gln Arg 
            20                  25                  30          


Leu Asn Pro Glu Gln Arg Asn Leu Tyr Arg Asp Val Met Leu Glu Asn 
        35                  40                  45              


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


Val Ile Leu Arg Leu Glu Gln Gly Lys Glu Pro Trp Leu Glu Glu Glu 
65                  70                  75                  80  


Glu Val Leu Gly Ser Gly Arg Ala Glu Lys Asn Gly Asp Ile Gly Gly 
                85                  90                  95      


Gln Ile Trp Lys Pro Lys Asp Val Lys Glu Ser Leu Tyr Pro Thr Phe 
            100                 105                 110         


Leu Tyr Lys Val Val Gly Gly Ser Gly Gly Ser Pro Lys Lys Lys Arg 
        115                 120                 125             


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


Gly Ile Ala Thr Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly 
145                 150                 155                 160 


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


Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys 
            180                 185                 190         


Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu 
        195                 200                 205             


Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys 
    210                 215                 220                 


Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys 
225                 230                 235                 240 


Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu 
                245                 250                 255     


Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp 
            260                 265                 270         


Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys 
        275                 280                 285             


Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu 
    290                 295                 300                 


Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly 
305                 310                 315                 320 


Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu 
                325                 330                 335     


Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser 
            340                 345                 350         


Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg 
        355                 360                 365             


Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly 
    370                 375                 380                 


Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe 
385                 390                 395                 400 


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


Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp 
            420                 425                 430         


Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile 
        435                 440                 445             


Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro 
    450                 455                 460                 


Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu 
465                 470                 475                 480 


Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys 
                485                 490                 495     


Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp 
            500                 505                 510         


Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu 
        515                 520                 525             


Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu 
    530                 535                 540                 


Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His 
545                 550                 555                 560 


Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp 
                565                 570                 575     


Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu 
            580                 585                 590         


Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser 
        595                 600                 605             


Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp 
    610                 615                 620                 


Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile 
625                 630                 635                 640 


Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu 
                645                 650                 655     


Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu 
            660                 665                 670         


Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu 
        675                 680                 685             


Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn 
    690                 695                 700                 


Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile 
705                 710                 715                 720 


Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn 
                725                 730                 735     


Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys 
            740                 745                 750         


Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val 
        755                 760                 765             


Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu 
    770                 775                 780                 


Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys 
785                 790                 795                 800 


Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn 
                805                 810                 815     


Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys 
            820                 825                 830         


Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp 
        835                 840                 845             


Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln 
    850                 855                 860                 


Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala 
865                 870                 875                 880 


Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val 
                885                 890                 895     


Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala 
            900                 905                 910         


Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg 
        915                 920                 925             


Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu 
    930                 935                 940                 


Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr 
945                 950                 955                 960 


Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu 
                965                 970                 975     


Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp Ala Ile Val Pro Gln 
            980                 985                 990         


Ser Phe Leu Lys Asp Asp Ser Ile  Asp Asn Lys Val Leu  Thr Arg Ser 
        995                 1000                 1005             


Asp Lys  Asn Arg Gly Lys Ser  Asp Asn Val Pro Ser  Glu Glu Val 
    1010                 1015                 1020             


Val Lys  Lys Met Lys Asn Tyr  Trp Arg Gln Leu Leu  Asn Ala Lys 
    1025                 1030                 1035             


Leu Ile  Thr Gln Arg Lys Phe  Asp Asn Leu Thr Lys  Ala Glu Arg 
    1040                 1045                 1050             


Gly Gly  Leu Ser Glu Leu Asp  Lys Ala Gly Phe Ile  Lys Arg Gln 
    1055                 1060                 1065             


Leu Val  Glu Thr Arg Gln Ile  Thr Lys His Val Ala  Gln Ile Leu 
    1070                 1075                 1080             


Asp Ser  Arg Met Asn Thr Lys  Tyr Asp Glu Asn Asp  Lys Leu Ile 
    1085                 1090                 1095             


Arg Glu  Val Lys Val Ile Thr  Leu Lys Ser Lys Leu  Val Ser Asp 
    1100                 1105                 1110             


Phe Arg  Lys Asp Phe Gln Phe  Tyr Lys Val Arg Glu  Ile Asn Asn 
    1115                 1120                 1125             


Tyr His  His Ala His Asp Ala  Tyr Leu Asn Ala Val  Val Gly Thr 
    1130                 1135                 1140             


Ala Leu  Ile Lys Lys Tyr Pro  Lys Leu Glu Ser Glu  Phe Val Tyr 
    1145                 1150                 1155             


Gly Asp  Tyr Lys Val Tyr Asp  Val Arg Lys Met Ile  Ala Lys Ser 
    1160                 1165                 1170             


Glu Gln  Glu Ile Gly Lys Ala  Thr Ala Lys Tyr Phe  Phe Tyr Ser 
    1175                 1180                 1185             


Asn Ile  Met Asn Phe Phe Lys  Thr Glu Ile Thr Leu  Ala Asn Gly 
    1190                 1195                 1200             


Glu Ile  Arg Lys Arg Pro Leu  Ile Glu Thr Asn Gly  Glu Thr Gly 
    1205                 1210                 1215             


Glu Ile  Val Trp Asp Lys Gly  Arg Asp Phe Ala Thr  Val Arg Lys 
    1220                 1225                 1230             


Val Leu  Ser Met Pro Gln Val  Asn Ile Val Lys Lys  Thr Glu Val 
    1235                 1240                 1245             


Gln Thr  Gly Gly Phe Ser Lys  Glu Ser Ile Leu Pro  Lys Arg Asn 
    1250                 1255                 1260             


Ser Asp  Lys Leu Ile Ala Arg  Lys Lys Asp Trp Asp  Pro Lys Lys 
    1265                 1270                 1275             


Tyr Gly  Gly Phe Asp Ser Pro  Thr Val Ala Tyr Ser  Val Leu Val 
    1280                 1285                 1290             


Val Ala  Lys Val Glu Lys Gly  Lys Ser Lys Lys Leu  Lys Ser Val 
    1295                 1300                 1305             


Lys Glu  Leu Leu Gly Ile Thr  Ile Met Glu Arg Ser  Ser Phe Glu 
    1310                 1315                 1320             


Lys Asn  Pro Ile Asp Phe Leu  Glu Ala Lys Gly Tyr  Lys Glu Val 
    1325                 1330                 1335             


Lys Lys  Asp Leu Ile Ile Lys  Leu Pro Lys Tyr Ser  Leu Phe Glu 
    1340                 1345                 1350             


Leu Glu  Asn Gly Arg Lys Arg  Met Leu Ala Ser Ala  Gly Glu Leu 
    1355                 1360                 1365             


Gln Lys  Gly Asn Glu Leu Ala  Leu Pro Ser Lys Tyr  Val Asn Phe 
    1370                 1375                 1380             


Leu Tyr  Leu Ala Ser His Tyr  Glu Lys Leu Lys Gly  Ser Pro Glu 
    1385                 1390                 1395             


Asp Asn  Glu Gln Lys Gln Leu  Phe Val Glu Gln His  Lys His Tyr 
    1400                 1405                 1410             


Leu Asp  Glu Ile Ile Glu Gln  Ile Ser Glu Phe Ser  Lys Arg Val 
    1415                 1420                 1425             


Ile Leu  Ala Asp Ala Asn Leu  Asp Lys Val Leu Ser  Ala Tyr Asn 
    1430                 1435                 1440             


Lys His  Arg Asp Lys Pro Ile  Arg Glu Gln Ala Glu  Asn Ile Ile 
    1445                 1450                 1455             


His Leu  Phe Thr Leu Thr Asn  Leu Gly Ala Pro Ala  Ala Phe Lys 
    1460                 1465                 1470             


Tyr Phe  Asp Thr Thr Ile Asp  Arg Lys Arg Tyr Thr  Ser Thr Lys 
    1475                 1480                 1485             


Glu Val  Leu Asp Ala Thr Leu  Ile His Gln Ser Ile  Thr Gly Leu 
    1490                 1495                 1500             


Tyr Glu  Thr Arg Ile Asp Leu  Ser Gln Leu Gly Gly  Asp Ala Tyr 
    1505                 1510                 1515             


Pro Tyr  Asp Val Pro Asp Tyr  Ala Ser Leu Gly Ser  Gly Ser Pro 
    1520                 1525                 1530             


Lys Lys  Lys Arg Lys Val Glu  Asp Pro Lys Lys Lys  Arg Lys Val 
    1535                 1540                 1545             


Asp Gly  
    1550 


<210>  15
<211>  554
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic construct


<220>
<221>  misc_feature
<222>  (531)..(554)
<223>  Flanking

<220>
<221>  misc_feature
<223>  CMV promoter + enhancer

<400>  15
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt       60

gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca      120

atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc      180

aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta      240

catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac      300

catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg      360

atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg      420

ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt      480

acggtgggag gtctatataa gcagagctct ctggctaact gtcgggatca acaagtttgt      540

acaaaaaagt tggc                                                        554


<210>  16
<211>  321
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (1)..(8)
<223>  Flanking

<220>
<221>  MISC_FEATURE
<222>  (9)..(108)
<223>  ZIM3-KRAB

<220>
<221>  MISC_FEATURE
<222>  (109)..(117)
<223>  Flanking

<220>
<221>  MISC_FEATURE
<222>  (140)..(321)
<223>  PYL1

<400>  16

Thr Ser Leu Tyr Lys Lys Val Gly Met Asn Asn Ser Gln Gly Arg Val 
1               5                   10                  15      


Thr Phe Glu Asp Val Thr Val Asn Phe Thr Gln Gly Glu Trp Gln Arg 
            20                  25                  30          


Leu Asn Pro Glu Gln Arg Asn Leu Tyr Arg Asp Val Met Leu Glu Asn 
        35                  40                  45              


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


Val Ile Leu Arg Leu Glu Gln Gly Lys Glu Pro Trp Leu Glu Glu Glu 
65                  70                  75                  80  


Glu Val Leu Gly Ser Gly Arg Ala Glu Lys Asn Gly Asp Ile Gly Gly 
                85                  90                  95      


Gln Ile Trp Lys Pro Lys Asp Val Lys Glu Ser Leu Tyr Pro Thr Phe 
            100                 105                 110         


Leu Tyr Lys Val Val Asp Ile Gln His Ser Gly Gly Arg Ser Ser Gly 
        115                 120                 125             


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


Thr Gln Asp Glu Phe Thr Gln Leu Ser Gln Ser Ile Ala Glu Phe His 
145                 150                 155                 160 


Thr Tyr Gln Leu Gly Asn Gly Arg Cys Ser Ser Leu Leu Ala Gln Arg 
                165                 170                 175     


Ile His Ala Pro Pro Glu Thr Val Trp Ser Val Val Arg Arg Phe Asp 
            180                 185                 190         


Arg Pro Gln Ile Tyr Lys His Phe Ile Lys Ser Cys Asn Val Ser Glu 
        195                 200                 205             


Asp Phe Glu Met Arg Val Gly Cys Thr Arg Asp Val Asn Val Ile Ser 
    210                 215                 220                 


Gly Leu Pro Ala Asn Thr Ser Arg Glu Arg Leu Asp Leu Leu Asp Asp 
225                 230                 235                 240 


Asp Arg Arg Val Thr Gly Phe Ser Ile Thr Gly Gly Glu His Arg Leu 
                245                 250                 255     


Arg Asn Tyr Lys Ser Val Thr Thr Val His Arg Phe Glu Lys Glu Glu 
            260                 265                 270         


Glu Glu Glu Arg Ile Trp Thr Val Val Leu Glu Ser Tyr Val Val Asp 
        275                 280                 285             


Val Pro Glu Gly Asn Ser Glu Glu Asp Thr Arg Leu Phe Ala Asp Thr 
    290                 295                 300                 


Val Ile Arg Leu Asn Leu Gln Lys Leu Ala Ser Ile Thr Glu Ala Met 
305                 310                 315                 320 


Asn 
    


<210>  17
<211>  1749
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct


<220>
<221>  MISC_FEATURE
<222>  (1)..(1368)
<223>  dCas9

<220>
<221>  MISC_FEATURE
<222>  (1370)..(1378)
<223>  HA

<220>
<221>  MISC_FEATURE
<222>  (1385)..(1391)
<223>  NLS

<220>
<221>  MISC_FEATURE
<222>  (1394)..(1400)
<223>  NLS

<220>
<221>  MISC_FEATURE
<222>  (1414)..(1648)
<223>  mCherry

<220>
<221>  MISC_FEATURE
<222>  (1654)..(1749)
<223>  ZIM3-KRAB

<400>  17

Met Asp Lys Lys Tyr Ser Ile Gly Leu Ala Ile Gly Thr Asn Ser Val 
1               5                   10                  15      


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
            20                  25                  30          


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
        35                  40                  45              


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
    50                  55                  60                  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
65                  70                  75                  80  


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
                85                  90                  95      


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
            100                 105                 110         


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
        115                 120                 125             


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
    130                 135                 140                 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
145                 150                 155                 160 


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


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
            180                 185                 190         


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


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
    210                 215                 220                 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
225                 230                 235                 240 


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


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
            260                 265                 270         


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
        275                 280                 285             


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
    290                 295                 300                 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
305                 310                 315                 320 


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
                325                 330                 335     


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
            340                 345                 350         


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
        355                 360                 365             


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
    370                 375                 380                 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
385                 390                 395                 400 


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
                405                 410                 415     


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
            420                 425                 430         


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
        435                 440                 445             


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
    450                 455                 460                 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
465                 470                 475                 480 


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
                485                 490                 495     


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
            500                 505                 510         


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
        515                 520                 525             


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
    530                 535                 540                 


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


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
                565                 570                 575     


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
            580                 585                 590         


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
        595                 600                 605             


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
    610                 615                 620                 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
625                 630                 635                 640 


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
                645                 650                 655     


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
            660                 665                 670         


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
        675                 680                 685             


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
    690                 695                 700                 


Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu 
705                 710                 715                 720 


His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly 
                725                 730                 735     


Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly 
            740                 745                 750         


Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln 
        755                 760                 765             


Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile 
    770                 775                 780                 


Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro 
785                 790                 795                 800 


Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu 
                805                 810                 815     


Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg 
            820                 825                 830         


Leu Ser Asp Tyr Asp Val Asp Ala Ile Val Pro Gln Ser Phe Leu Lys 
        835                 840                 845             


Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg 
    850                 855                 860                 


Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys 
865                 870                 875                 880 


Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys 
                885                 890                 895     


Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp 
            900                 905                 910         


Lys Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr 
        915                 920                 925             


Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp 
    930                 935                 940                 


Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser 
945                 950                 955                 960 


Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg 
                965                 970                 975     


Glu Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val 
            980                 985                 990         


Val Gly Thr Ala Leu Ile Lys Lys  Tyr Pro Lys Leu Glu  Ser Glu Phe 
        995                 1000                 1005             


Val Tyr  Gly Asp Tyr Lys Val  Tyr Asp Val Arg Lys  Met Ile Ala 
    1010                 1015                 1020             


Lys Ser  Glu Gln Glu Ile Gly  Lys Ala Thr Ala Lys  Tyr Phe Phe 
    1025                 1030                 1035             


Tyr Ser  Asn Ile Met Asn Phe  Phe Lys Thr Glu Ile  Thr Leu Ala 
    1040                 1045                 1050             


Asn Gly  Glu Ile Arg Lys Arg  Pro Leu Ile Glu Thr  Asn Gly Glu 
    1055                 1060                 1065             


Thr Gly  Glu Ile Val Trp Asp  Lys Gly Arg Asp Phe  Ala Thr Val 
    1070                 1075                 1080             


Arg Lys  Val Leu Ser Met Pro  Gln Val Asn Ile Val  Lys Lys Thr 
    1085                 1090                 1095             


Glu Val  Gln Thr Gly Gly Phe  Ser Lys Glu Ser Ile  Leu Pro Lys 
    1100                 1105                 1110             


Arg Asn  Ser Asp Lys Leu Ile  Ala Arg Lys Lys Asp  Trp Asp Pro 
    1115                 1120                 1125             


Lys Lys  Tyr Gly Gly Phe Asp  Ser Pro Thr Val Ala  Tyr Ser Val 
    1130                 1135                 1140             


Leu Val  Val Ala Lys Val Glu  Lys Gly Lys Ser Lys  Lys Leu Lys 
    1145                 1150                 1155             


Ser Val  Lys Glu Leu Leu Gly  Ile Thr Ile Met Glu  Arg Ser Ser 
    1160                 1165                 1170             


Phe Glu  Lys Asn Pro Ile Asp  Phe Leu Glu Ala Lys  Gly Tyr Lys 
    1175                 1180                 1185             


Glu Val  Lys Lys Asp Leu Ile  Ile Lys Leu Pro Lys  Tyr Ser Leu 
    1190                 1195                 1200             


Phe Glu  Leu Glu Asn Gly Arg  Lys Arg Met Leu Ala  Ser Ala Gly 
    1205                 1210                 1215             


Glu Leu  Gln Lys Gly Asn Glu  Leu Ala Leu Pro Ser  Lys Tyr Val 
    1220                 1225                 1230             


Asn Phe  Leu Tyr Leu Ala Ser  His Tyr Glu Lys Leu  Lys Gly Ser 
    1235                 1240                 1245             


Pro Glu  Asp Asn Glu Gln Lys  Gln Leu Phe Val Glu  Gln His Lys 
    1250                 1255                 1260             


His Tyr  Leu Asp Glu Ile Ile  Glu Gln Ile Ser Glu  Phe Ser Lys 
    1265                 1270                 1275             


Arg Val  Ile Leu Ala Asp Ala  Asn Leu Asp Lys Val  Leu Ser Ala 
    1280                 1285                 1290             


Tyr Asn  Lys His Arg Asp Lys  Pro Ile Arg Glu Gln  Ala Glu Asn 
    1295                 1300                 1305             


Ile Ile  His Leu Phe Thr Leu  Thr Asn Leu Gly Ala  Pro Ala Ala 
    1310                 1315                 1320             


Phe Lys  Tyr Phe Asp Thr Thr  Ile Asp Arg Lys Arg  Tyr Thr Ser 
    1325                 1330                 1335             


Thr Lys  Glu Val Leu Asp Ala  Thr Leu Ile His Gln  Ser Ile Thr 
    1340                 1345                 1350             


Gly Leu  Tyr Glu Thr Arg Ile  Asp Leu Ser Gln Leu  Gly Gly Asp 
    1355                 1360                 1365             


Ala Tyr  Pro Tyr Asp Val Pro  Asp Tyr Ala Ser Leu  Gly Ser Gly 
    1370                 1375                 1380             


Ser Pro  Lys Lys Lys Arg Lys  Val Glu Asp Pro Lys  Lys Lys Arg 
    1385                 1390                 1395             


Lys Val  Asp Gly Ile Gly Ser  Gly Ser Asn Gly Ser  Ser Gly Ser 
    1400                 1405                 1410             


Met Val  Ser Lys Gly Glu Glu  Asp Asn Met Ala Ile  Ile Lys Glu 
    1415                 1420                 1425             


Phe Met  Arg Phe Lys Val His  Met Glu Gly Ser Val  Asn Gly His 
    1430                 1435                 1440             


Glu Phe  Glu Ile Glu Gly Glu  Gly Glu Gly Arg Pro  Tyr Glu Gly 
    1445                 1450                 1455             


Thr Gln  Thr Ala Lys Leu Lys  Val Thr Lys Gly Gly  Pro Leu Pro 
    1460                 1465                 1470             


Phe Ala  Trp Asp Ile Leu Ser  Pro Gln Phe Met Tyr  Gly Ser Lys 
    1475                 1480                 1485             


Ala Tyr  Val Lys His Pro Ala  Asp Ile Pro Asp Tyr  Leu Lys Leu 
    1490                 1495                 1500             


Ser Phe  Pro Glu Gly Phe Lys  Trp Glu Arg Val Met  Asn Phe Glu 
    1505                 1510                 1515             


Asp Gly  Gly Val Val Thr Val  Thr Gln Asp Ser Ser  Leu Gln Asp 
    1520                 1525                 1530             


Gly Glu  Phe Ile Tyr Lys Val  Lys Leu Arg Gly Thr  Asn Phe Pro 
    1535                 1540                 1545             


Ser Asp  Gly Pro Val Met Gln  Lys Lys Thr Met Gly  Trp Glu Ala 
    1550                 1555                 1560             


Ser Ser  Glu Arg Met Tyr Pro  Glu Asp Gly Ala Leu  Lys Gly Glu 
    1565                 1570                 1575             


Ile Lys  Gln Arg Leu Lys Leu  Lys Asp Gly Gly His  Tyr Asp Ala 
    1580                 1585                 1590             


Glu Val  Lys Thr Thr Tyr Lys  Ala Lys Lys Pro Val  Gln Leu Pro 
    1595                 1600                 1605             


Gly Ala  Tyr Asn Val Asn Ile  Lys Leu Asp Ile Thr  Ser His Asn 
    1610                 1615                 1620             


Glu Asp  Tyr Thr Ile Val Glu  Gln Tyr Glu Arg Ala  Glu Gly Arg 
    1625                 1630                 1635             


His Ser  Thr Gly Gly Met Asp  Glu Leu Tyr Gly Gly  Gly Gly Gly 
    1640                 1645                 1650             


Met Gly  Arg Val Thr Phe Glu  Asp Val Thr Val Asn  Phe Thr Gln 
    1655                 1660                 1665             


Gly Glu  Trp Gln Arg Leu Asn  Pro Glu Gln Arg Asn  Leu Tyr Arg 
    1670                 1675                 1680             


Asp Val  Met Leu Glu Asn Tyr  Ser Asn Leu Val Ser  Val Gly Gln 
    1685                 1690                 1695             


Gly Glu  Thr Thr Lys Pro Asp  Val Ile Leu Arg Leu  Glu Gln Gly 
    1700                 1705                 1710             


Lys Glu  Pro Trp Leu Glu Glu  Glu Glu Val Leu Gly  Ser Gly Arg 
    1715                 1720                 1725             


Ala Glu  Lys Asn Gly Asp Ile  Gly Gly Gln Ile Trp  Lys Pro Lys 
    1730                 1735                 1740             


Asp Val  Lys Glu Ser Leu 
    1745                 


<210>  18
<211>  95
<212>  PRT
<213>  Homo sapiens

<400>  18

Met Ala Gly Ser Gln Phe Pro Asp Phe Lys His Leu Gly Thr Phe Leu 
1               5                   10                  15      


Val Phe Glu Glu Leu Val Thr Phe Glu Asp Val Leu Val Asp Phe Ser 
            20                  25                  30          


Pro Glu Glu Leu Ser Ser Leu Ser Ala Ala Gln Arg Asn Leu Tyr Arg 
        35                  40                  45              


Glu Val Met Leu Glu Asn Tyr Arg Asn Leu Val Ser Leu Gly His Gln 
    50                  55                  60                  


Phe Ser Lys Pro Asp Ile Ile Ser Arg Leu Glu Glu Glu Glu Ser Tyr 
65                  70                  75                  80  


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


