                         SEQUENCE LISTING

<110>  Northwestern University
       Kiyokawa, Hiroaki
       Mishra, Rama K
       Luan, Chi-Hao
 
<120>  HECT E3 UBIQUITIN LIAGASE INHIBITORS AND USES THEREOF

<130>  702581.02093

<150>  63/140,077
<151>  2021-01-21

<150>  63/200,239
<151>  2021-02-24

<160>  6     

<170>  PatentIn version 3.5

<210>  1
<211>  685
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
1               5                   10                  15      


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


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
        35                  40                  45              


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
    50                  55                  60                  


Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe 
65                  70                  75                  80  


Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser 
                85                  90                  95      


Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile 
            100                 105                 110         


Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp 
        115                 120                 125             


Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His 
    130                 135                 140                 


Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu 
145                 150                 155                 160 


Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu 
                165                 170                 175     


Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln 
            180                 185                 190         


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


Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg 
    210                 215                 220                 


Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr 
225                 230                 235                 240 


Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala 
                245                 250                 255     


Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile 
            260                 265                 270         


Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn 
        275                 280                 285             


Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly 
    290                 295                 300                 


Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
305                 310                 315                 320 


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


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
            340                 345                 350         


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
        355                 360                 365             


Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe 
    370                 375                 380                 


Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser 
385                 390                 395                 400 


Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile 
                405                 410                 415     


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


Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His 
        435                 440                 445             


Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu 
    450                 455                 460                 


Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu 
465                 470                 475                 480 


Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln 
                485                 490                 495     


Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu 
            500                 505                 510         


Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg 
        515                 520                 525             


Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr 
    530                 535                 540                 


Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala 
545                 550                 555                 560 


Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile 
                565                 570                 575     


Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn 
            580                 585                 590         


Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly 
        595                 600                 605             


Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
    610                 615                 620                 


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
625                 630                 635                 640 


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
                645                 650                 655     


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
            660                 665                 670         


Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Val 
        675                 680                 685 


<210>  2
<211>  533
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
1               5                   10                  15      


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


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
        35                  40                  45              


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
    50                  55                  60                  


Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe 
65                  70                  75                  80  


Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser 
                85                  90                  95      


Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile 
            100                 105                 110         


Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp 
        115                 120                 125             


Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His 
    130                 135                 140                 


Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu 
145                 150                 155                 160 


Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu 
                165                 170                 175     


Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln 
            180                 185                 190         


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


Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg 
    210                 215                 220                 


Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr 
225                 230                 235                 240 


Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala 
                245                 250                 255     


Lys Val Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile 
            260                 265                 270         


Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn 
        275                 280                 285             


Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly 
    290                 295                 300                 


Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
305                 310                 315                 320 


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


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
            340                 345                 350         


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
        355                 360                 365             


Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe 
    370                 375                 380                 


Val Lys Thr Leu Thr Gly Lys Ala Ile Thr Leu Glu Val Glu Pro Ser 
385                 390                 395                 400 


Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile 
                405                 410                 415     


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


Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His 
        435                 440                 445             


Leu Val Leu Arg Leu Arg Gly Gly Met Gln Ile Phe Val Lys Thr Leu 
    450                 455                 460                 


Thr Gly Lys Thr Ile Thr Leu Glu Val Glu Pro Ser Asp Thr Ile Glu 
465                 470                 475                 480 


Asn Val Lys Ala Lys Ile Gln Asp Lys Glu Gly Ile Pro Pro Asp Gln 
                485                 490                 495     


Gln Arg Leu Ile Phe Ala Gly Lys Gln Leu Glu Asp Gly Arg Thr Leu 
            500                 505                 510         


Ser Asp Tyr Asn Ile Gln Lys Glu Ser Thr Leu His Leu Val Leu Arg 
        515                 520                 525             


Leu Arg Gly Gly Val 
    530             


<210>  3
<211>  76
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
1               5                   10                  15      


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


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
        35                  40                  45              


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
    50                  55                  60                  


Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly 
65                  70                  75      


<210>  4
<211>  1058
<212>  PRT
<213>  Homo sapiens

<400>  4

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


Pro Lys Pro Gly Ser Asn Cys Ser Pro Ala Gln Ser Val Leu Ser Glu 
            20                  25                  30          


Val Pro Ser Val Pro Thr Asn Gly Met Ala Lys Asn Gly Ser Glu Ala 
        35                  40                  45              


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


Glu Ala Met Lys Arg Leu Gln Thr Ser Ser Val Leu Val Ser Gly Leu 
65                  70                  75                  80  


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


Lys Ala Val Thr Leu His Asp Gln Gly Thr Ala Gln Trp Ala Asp Leu 
            100                 105                 110         


Ser Ser Gln Phe Tyr Leu Arg Glu Glu Asp Ile Gly Lys Asn Arg Ala 
        115                 120                 125             


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


Thr Ala Tyr Thr Gly Pro Leu Val Glu Asp Phe Leu Ser Gly Phe Gln 
145                 150                 155                 160 


Val Val Val Leu Thr Asn Thr Pro Leu Glu Asp Gln Leu Arg Val Gly 
                165                 170                 175     


Glu Phe Cys His Asn Arg Gly Ile Lys Leu Val Val Ala Asp Thr Arg 
            180                 185                 190         


Gly Leu Phe Gly Gln Leu Phe Cys Asp Phe Gly Glu Glu Met Ile Leu 
        195                 200                 205             


Thr Asp Ser Asn Gly Glu Gln Pro Leu Ser Ala Met Val Ser Met Val 
    210                 215                 220                 


Thr Lys Asp Asn Pro Gly Val Val Thr Cys Leu Asp Glu Ala Arg His 
225                 230                 235                 240 


Gly Phe Glu Ser Gly Asp Phe Val Ser Phe Ser Glu Val Gln Gly Met 
                245                 250                 255     


Val Glu Leu Asn Gly Asn Gln Pro Met Glu Ile Lys Val Leu Gly Pro 
            260                 265                 270         


Tyr Thr Phe Ser Ile Cys Asp Thr Ser Asn Phe Ser Asp Tyr Ile Arg 
        275                 280                 285             


Gly Gly Ile Val Ser Gln Val Lys Val Pro Lys Lys Ile Ser Phe Lys 
    290                 295                 300                 


Ser Leu Val Ala Ser Leu Ala Glu Pro Asp Phe Val Val Thr Asp Phe 
305                 310                 315                 320 


Ala Lys Phe Ser Arg Pro Ala Gln Leu His Ile Gly Phe Gln Ala Leu 
                325                 330                 335     


His Gln Phe Cys Ala Gln His Gly Arg Pro Pro Arg Pro Arg Asn Glu 
            340                 345                 350         


Glu Asp Ala Ala Glu Leu Val Ala Leu Ala Gln Ala Val Asn Ala Arg 
        355                 360                 365             


Ala Leu Pro Ala Val Gln Gln Asn Asn Leu Asp Glu Asp Leu Ile Arg 
    370                 375                 380                 


Lys Leu Ala Tyr Val Ala Ala Gly Asp Leu Ala Pro Ile Asn Ala Phe 
385                 390                 395                 400 


Ile Gly Gly Leu Ala Ala Gln Glu Val Met Lys Ala Cys Ser Gly Lys 
                405                 410                 415     


Phe Met Pro Ile Met Gln Trp Leu Tyr Phe Asp Ala Leu Glu Cys Leu 
            420                 425                 430         


Pro Glu Asp Lys Glu Val Leu Thr Glu Asp Lys Cys Leu Gln Arg Gln 
        435                 440                 445             


Asn Arg Tyr Asp Gly Gln Val Ala Val Phe Gly Ser Asp Leu Gln Glu 
    450                 455                 460                 


Lys Leu Gly Lys Gln Lys Tyr Phe Leu Val Gly Ala Gly Ala Ile Gly 
465                 470                 475                 480 


Cys Glu Leu Leu Lys Asn Phe Ala Met Ile Gly Leu Gly Cys Gly Glu 
                485                 490                 495     


Gly Gly Glu Ile Ile Val Thr Asp Met Asp Thr Ile Glu Lys Ser Asn 
            500                 505                 510         


Leu Asn Arg Gln Phe Leu Phe Arg Pro Trp Asp Val Thr Lys Leu Lys 
        515                 520                 525             


Ser Asp Thr Ala Ala Ala Ala Val Arg Gln Met Asn Pro His Ile Arg 
    530                 535                 540                 


Val Thr Ser His Gln Asn Arg Val Gly Pro Asp Thr Glu Arg Ile Tyr 
545                 550                 555                 560 


Asp Asp Asp Phe Phe Gln Asn Leu Asp Gly Val Ala Asn Ala Leu Asp 
                565                 570                 575     


Asn Val Asp Ala Arg Met Tyr Met Asp Arg Arg Cys Val Tyr Tyr Arg 
            580                 585                 590         


Lys Pro Leu Leu Glu Ser Gly Thr Leu Gly Thr Lys Gly Asn Val Gln 
        595                 600                 605             


Val Val Ile Pro Phe Leu Thr Glu Ser Tyr Ser Ser Ser Gln Asp Pro 
    610                 615                 620                 


Pro Glu Lys Ser Ile Pro Ile Cys Thr Leu Lys Asn Phe Pro Asn Ala 
625                 630                 635                 640 


Ile Glu His Thr Leu Gln Trp Ala Arg Asp Glu Phe Glu Gly Leu Phe 
                645                 650                 655     


Lys Gln Pro Ala Glu Asn Val Asn Gln Tyr Leu Thr Asp Pro Lys Phe 
            660                 665                 670         


Val Glu Arg Thr Leu Arg Leu Ala Gly Thr Gln Pro Leu Glu Val Leu 
        675                 680                 685             


Glu Ala Val Gln Arg Ser Leu Val Leu Gln Arg Pro Gln Thr Trp Ala 
    690                 695                 700                 


Asp Cys Val Thr Trp Ala Cys His His Trp His Thr Gln Tyr Ser Asn 
705                 710                 715                 720 


Asn Ile Arg Gln Leu Leu His Asn Phe Pro Pro Asp Gln Leu Thr Ser 
                725                 730                 735     


Ser Gly Ala Pro Phe Trp Ser Gly Pro Lys Arg Cys Pro His Pro Leu 
            740                 745                 750         


Thr Phe Asp Val Asn Asn Pro Leu His Leu Asp Tyr Val Met Ala Ala 
        755                 760                 765             


Ala Asn Leu Phe Ala Gln Thr Tyr Gly Leu Thr Gly Ser Gln Asp Arg 
    770                 775                 780                 


Ala Ala Val Ala Thr Phe Leu Gln Ser Val Gln Val Pro Glu Phe Thr 
785                 790                 795                 800 


Pro Lys Ser Gly Val Lys Ile His Val Ser Asp Gln Glu Leu Gln Ser 
                805                 810                 815     


Ala Asn Ala Ser Val Asp Asp Ser Arg Leu Glu Glu Leu Lys Ala Thr 
            820                 825                 830         


Leu Pro Ser Pro Asp Lys Leu Pro Gly Phe Lys Met Tyr Pro Ile Asp 
        835                 840                 845             


Phe Glu Lys Asp Asp Asp Ser Asn Phe His Met Asp Phe Ile Val Ala 
    850                 855                 860                 


Ala Ser Asn Leu Arg Ala Glu Asn Tyr Asp Ile Pro Ser Ala Asp Arg 
865                 870                 875                 880 


His Lys Ser Lys Leu Ile Ala Gly Lys Ile Ile Pro Ala Ile Ala Thr 
                885                 890                 895     


Thr Thr Ala Ala Val Val Gly Leu Val Cys Leu Glu Leu Tyr Lys Val 
            900                 905                 910         


Val Gln Gly His Arg Gln Leu Asp Ser Tyr Lys Asn Gly Phe Leu Asn 
        915                 920                 925             


Leu Ala Leu Pro Phe Phe Gly Phe Ser Glu Pro Leu Ala Ala Pro Arg 
    930                 935                 940                 


His Gln Tyr Tyr Asn Gln Glu Trp Thr Leu Trp Asp Arg Phe Glu Val 
945                 950                 955                 960 


Gln Gly Leu Gln Pro Asn Gly Glu Glu Met Thr Leu Lys Gln Phe Leu 
                965                 970                 975     


Asp Tyr Phe Lys Thr Glu His Lys Leu Glu Ile Thr Met Leu Ser Gln 
            980                 985                 990         


Gly Val Ser Met Leu Tyr Ser Phe  Phe Met Pro Ala Ala  Lys Leu Lys 
        995                 1000                 1005             


Glu Arg  Leu Asp Gln Pro Met  Thr Glu Ile Val Ser  Arg Val Ser 
    1010                 1015                 1020             


Lys Arg  Lys Leu Gly Arg His  Val Arg Ala Leu Val  Leu Glu Leu 
    1025                 1030                 1035             


Cys Cys  Asn Asp Glu Ser Gly  Glu Asp Val Glu Val  Pro Tyr Val 
    1040                 1045                 1050             


Arg Tyr  Thr Ile Arg 
    1055             


<210>  5
<211>  154
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Ala Ala Ser Arg Arg Leu Met Lys Glu Leu Glu Glu Ile Arg Lys 
1               5                   10                  15      


Cys Gly Met Lys Asn Phe Arg Asn Ile Gln Val Asp Glu Ala Asn Leu 
            20                  25                  30          


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


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


Pro Pro Lys Ile Thr Phe Lys Thr Lys Ile Tyr His Pro Asn Ile Asp 
65                  70                  75                  80  


Glu Lys Gly Gln Val Cys Leu Pro Val Ile Ser Ala Glu Asn Trp Lys 
                85                  90                  95      


Pro Ala Thr Lys Thr Asp Gln Val Ile Gln Ser Leu Ile Ala Leu Val 
            100                 105                 110         


Asn Asp Pro Gln Pro Glu His Pro Leu Arg Ala Asp Leu Ala Glu Glu 
        115                 120                 125             


Tyr Ser Lys Asp Arg Lys Lys Phe Cys Lys Asn Ala Glu Glu Phe Thr 
    130                 135                 140                 


Lys Lys Tyr Gly Glu Lys Arg Pro Val Asp 
145                 150                 


<210>  6
<211>  852
<212>  PRT
<213>  Homo sapiens

<400>  6

Met Lys Arg Ala Ala Ala Lys His Leu Ile Glu Arg Tyr Tyr His Gln 
1               5                   10                  15      


Leu Thr Glu Gly Cys Gly Asn Glu Ala Cys Thr Asn Glu Phe Cys Ala 
            20                  25                  30          


Ser Cys Pro Thr Phe Leu Arg Met Asp Asn Asn Ala Ala Ala Ile Lys 
        35                  40                  45              


Ala Leu Glu Leu Tyr Lys Ile Asn Ala Lys Leu Cys Asp Pro His Pro 
    50                  55                  60                  


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


Pro Asn Asn Ser Cys Ser Glu Ile Lys Met Asn Lys Lys Gly Ala Arg 
                85                  90                  95      


Ile Asp Phe Lys Asp Val Thr Tyr Leu Thr Glu Glu Lys Val Tyr Glu 
            100                 105                 110         


Ile Leu Glu Leu Cys Arg Glu Arg Glu Asp Tyr Ser Pro Leu Ile Arg 
        115                 120                 125             


Val Ile Gly Arg Val Phe Ser Ser Ala Glu Ala Leu Val Gln Ser Phe 
    130                 135                 140                 


Arg Lys Val Lys Gln His Thr Lys Glu Glu Leu Lys Ser Leu Gln Ala 
145                 150                 155                 160 


Lys Asp Glu Asp Lys Asp Glu Asp Glu Lys Glu Lys Ala Ala Cys Ser 
                165                 170                 175     


Ala Ala Ala Met Glu Glu Asp Ser Glu Ala Ser Ser Ser Arg Ile Gly 
            180                 185                 190         


Asp Ser Ser Gln Gly Asp Asn Asn Leu Gln Lys Leu Gly Pro Asp Asp 
        195                 200                 205             


Val Ser Val Asp Ile Asp Ala Ile Arg Arg Val Tyr Thr Arg Leu Leu 
    210                 215                 220                 


Ser Asn Glu Lys Ile Glu Thr Ala Phe Leu Asn Ala Leu Val Tyr Leu 
225                 230                 235                 240 


Ser Pro Asn Val Glu Cys Asp Leu Thr Tyr His Asn Val Tyr Ser Arg 
                245                 250                 255     


Asp Pro Asn Tyr Leu Asn Leu Phe Ile Ile Val Met Glu Asn Arg Asn 
            260                 265                 270         


Leu His Ser Pro Glu Tyr Leu Glu Met Ala Leu Pro Leu Phe Cys Lys 
        275                 280                 285             


Ala Met Ser Lys Leu Pro Leu Ala Ala Gln Gly Lys Leu Ile Arg Leu 
    290                 295                 300                 


Trp Ser Lys Tyr Asn Ala Asp Gln Ile Arg Arg Met Met Glu Thr Phe 
305                 310                 315                 320 


Gln Gln Leu Ile Thr Tyr Lys Val Ile Ser Asn Glu Phe Asn Ser Arg 
                325                 330                 335     


Asn Leu Val Asn Asp Asp Asp Ala Ile Val Ala Ala Ser Lys Cys Leu 
            340                 345                 350         


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


His Asn Glu Glu Asp Asp Glu Glu Pro Ile Pro Glu Ser Ser Glu Leu 
    370                 375                 380                 


Thr Leu Gln Glu Leu Leu Gly Glu Glu Arg Arg Asn Lys Lys Gly Pro 
385                 390                 395                 400 


Arg Val Asp Pro Leu Glu Thr Glu Leu Gly Val Lys Thr Leu Asp Cys 
                405                 410                 415     


Arg Lys Pro Leu Ile Pro Phe Glu Glu Phe Ile Asn Glu Pro Leu Asn 
            420                 425                 430         


Glu Val Leu Glu Met Asp Lys Asp Tyr Thr Phe Phe Lys Val Glu Thr 
        435                 440                 445             


Glu Asn Lys Phe Ser Phe Met Thr Cys Pro Phe Ile Leu Asn Ala Val 
    450                 455                 460                 


Thr Lys Asn Leu Gly Leu Tyr Tyr Asp Asn Arg Ile Arg Met Tyr Ser 
465                 470                 475                 480 


Glu Arg Arg Ile Thr Val Leu Tyr Ser Leu Val Gln Gly Gln Gln Leu 
                485                 490                 495     


Asn Pro Tyr Leu Arg Leu Lys Val Arg Arg Asp His Ile Ile Asp Asp 
            500                 505                 510         


Ala Leu Val Arg Leu Glu Met Ile Ala Met Glu Asn Pro Ala Asp Leu 
        515                 520                 525             


Lys Lys Gln Leu Tyr Val Glu Phe Glu Gly Glu Gln Gly Val Asp Glu 
    530                 535                 540                 


Gly Gly Val Ser Lys Glu Phe Phe Gln Leu Val Val Glu Glu Ile Phe 
545                 550                 555                 560 


Asn Pro Asp Ile Gly Met Phe Thr Tyr Asp Glu Ser Thr Lys Leu Phe 
                565                 570                 575     


Trp Phe Asn Pro Ser Ser Phe Glu Thr Glu Gly Gln Phe Thr Leu Ile 
            580                 585                 590         


Gly Ile Val Leu Gly Leu Ala Ile Tyr Asn Asn Cys Ile Leu Asp Val 
        595                 600                 605             


His Phe Pro Met Val Val Tyr Arg Lys Leu Met Gly Lys Lys Gly Thr 
    610                 615                 620                 


Phe Arg Asp Leu Gly Asp Ser His Pro Val Leu Tyr Gln Ser Leu Lys 
625                 630                 635                 640 


Asp Leu Leu Glu Tyr Glu Gly Asn Val Glu Asp Asp Met Met Ile Thr 
                645                 650                 655     


Phe Gln Ile Ser Gln Thr Asp Leu Phe Gly Asn Pro Met Met Tyr Asp 
            660                 665                 670         


Leu Lys Glu Asn Gly Asp Lys Ile Pro Ile Thr Asn Glu Asn Arg Lys 
        675                 680                 685             


Glu Phe Val Asn Leu Tyr Ser Asp Tyr Ile Leu Asn Lys Ser Val Glu 
    690                 695                 700                 


Lys Gln Phe Lys Ala Phe Arg Arg Gly Phe His Met Val Thr Asn Glu 
705                 710                 715                 720 


Ser Pro Leu Lys Tyr Leu Phe Arg Pro Glu Glu Ile Glu Leu Leu Ile 
                725                 730                 735     


Cys Gly Ser Arg Asn Leu Asp Phe Gln Ala Leu Glu Glu Thr Thr Glu 
            740                 745                 750         


Tyr Asp Gly Gly Tyr Thr Arg Asp Ser Val Leu Ile Arg Glu Phe Trp 
        755                 760                 765             


Glu Ile Val His Ser Phe Thr Asp Glu Gln Lys Arg Leu Phe Leu Gln 
    770                 775                 780                 


Phe Thr Thr Gly Thr Asp Arg Ala Pro Val Gly Gly Leu Gly Lys Leu 
785                 790                 795                 800 


Lys Met Ile Ile Ala Lys Asn Gly Pro Asp Thr Glu Arg Leu Pro Thr 
                805                 810                 815     


Ser His Thr Cys Phe Asn Val Leu Leu Leu Pro Glu Tyr Ser Ser Lys 
            820                 825                 830         


Glu Lys Leu Lys Glu Arg Leu Leu Lys Ala Ile Thr Tyr Ala Lys Gly 
        835                 840                 845             


Phe Gly Met Leu 
    850         


