                         SEQUENCE LISTING

<110>  Autolus Ltd
 
<120>  SIGNALLING SYSTEM

<130>  Autolus Ltd

<150>  GB 1602571.0
<151>  2016-02-12

<160>  27    

<170>  PatentIn version 3.5

<210>  1
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 1

<400>  1

Lys Ser Lys Val Ile Asn Ser Ala Leu Glu Leu Leu Asn Glu Val Gly 
1               5                   10                  15      


Ile Glu Gly 
            


<210>  2
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 2

<400>  2

Thr Arg Lys Leu Ala Gln Lys Leu 
1               5               


<210>  3
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 3

<400>  3

Gln Pro Thr Leu Tyr 
1               5   


<210>  4
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 4

<400>  4

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


<210>  5
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 5

<400>  5

Trp Gln Asp Phe Leu Arg Asn Asn Ala Lys Ser Phe Arg Cys Ala Leu 
1               5                   10                  15      


Leu 
    


<210>  6
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 6

<400>  6

Gly Ala Lys Val His 
1               5   


<210>  7
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 7

<400>  7

Gln Tyr Glu Thr Leu Glu Asn Gln Leu Ala Phe Leu Cys Gln 
1               5                   10                  


<210>  8
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR alpha helix 8

<400>  8

Leu Glu Asn Ala Leu Tyr Ala Leu Ser Ala Val Gly His Phe Thr Leu 
1               5                   10                  15      


Gly Cys Val Leu Glu Asp Gln Glu His Gln Val Ala Lys Glu 
            20                  25                  30  


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

<220>
<223>  TetR alpha helix 9

<400>  9

Pro Leu Leu Arg Gln Ala Ile Glu Leu Phe Asp His 
1               5                   10          


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

<220>
<223>  TetR alpha helix 10

<400>  10

Ala Glu Pro Ala Phe Leu Phe Gly Leu Glu Leu Ile Ile Cys Gly Leu 
1               5                   10                  15      


Glu Lys Gln Leu 
            20  


<210>  11
<211>  177
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  truncated TetR lacking helix 1

<400>  11

Thr Arg Lys Leu Ala Gln Lys Leu Gly Val Glu Gln Pro Thr Leu Tyr 
1               5                   10                  15      


Trp His Val Lys Asn Lys Arg Ala Leu Leu Asp Ala Leu Ala Ile Glu 
            20                  25                  30          


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


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


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


Glu Lys Gln Tyr Glu Thr Leu Glu Asn Gln Leu Ala Phe Leu Cys Gln 
                85                  90                  95      


Gln Gly Phe Ser Leu Glu Asn Ala Leu Tyr Ala Leu Ser Ala Val Gly 
            100                 105                 110         


His Phe Thr Leu Gly Cys Val Leu Glu Asp Gln Glu His Gln Val Ala 
        115                 120                 125             


Lys Glu Glu Arg Glu Thr Pro Thr Thr Asp Ser Met Pro Pro Leu Leu 
    130                 135                 140                 


Arg Gln Ala Ile Glu Leu Phe Asp His Gln Gly Ala Glu Pro Ala Phe 
145                 150                 155                 160 


Leu Phe Gly Leu Glu Leu Ile Ile Cys Gly Leu Glu Lys Gln Leu Lys 
                165                 170                 175     


Cys 
    


<210>  12
<211>  166
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  truncated TetR lacking helix 1 and 2

<400>  12

Gln Pro Thr Leu Tyr Trp His Val Lys Asn Lys Arg Ala Leu Leu Asp 
1               5                   10                  15      


Ala Leu Ala Ile Glu Met Leu Asp Arg His His Thr His Phe Cys Pro 
            20                  25                  30          


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


Phe Arg Cys Ala Leu Leu Ser His Arg Asp Gly Ala Lys Val His Leu 
    50                  55                  60                  


Gly Thr Arg Pro Thr Glu Lys Gln Tyr Glu Thr Leu Glu Asn Gln Leu 
65                  70                  75                  80  


Ala Phe Leu Cys Gln Gln Gly Phe Ser Leu Glu Asn Ala Leu Tyr Ala 
                85                  90                  95      


Leu Ser Ala Val Gly His Phe Thr Leu Gly Cys Val Leu Glu Asp Gln 
            100                 105                 110         


Glu His Gln Val Ala Lys Glu Glu Arg Glu Thr Pro Thr Thr Asp Ser 
        115                 120                 125             


Met Pro Pro Leu Leu Arg Gln Ala Ile Glu Leu Phe Asp His Gln Gly 
    130                 135                 140                 


Ala Glu Pro Ala Phe Leu Phe Gly Leu Glu Leu Ile Ile Cys Gly Leu 
145                 150                 155                 160 


Glu Lys Gln Leu Lys Cys 
                165     


<210>  13
<211>  156
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  truncated TetR lacking helix 1, 2 and 3

<400>  13

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


His Thr His Phe Cys Pro Leu Glu Gly Glu Ser Trp Gln Asp Phe Leu 
            20                  25                  30          


Arg Asn Asn Ala Lys Ser Phe Arg Cys Ala Leu Leu Ser His Arg Asp 
        35                  40                  45              


Gly Ala Lys Val His Leu Gly Thr Arg Pro Thr Glu Lys Gln Tyr Glu 
    50                  55                  60                  


Thr Leu Glu Asn Gln Leu Ala Phe Leu Cys Gln Gln Gly Phe Ser Leu 
65                  70                  75                  80  


Glu Asn Ala Leu Tyr Ala Leu Ser Ala Val Gly His Phe Thr Leu Gly 
                85                  90                  95      


Cys Val Leu Glu Asp Gln Glu His Gln Val Ala Lys Glu Glu Arg Glu 
            100                 105                 110         


Thr Pro Thr Thr Asp Ser Met Pro Pro Leu Leu Arg Gln Ala Ile Glu 
        115                 120                 125             


Leu Phe Asp His Gln Gly Ala Glu Pro Ala Phe Leu Phe Gly Leu Glu 
    130                 135                 140                 


Leu Ile Ile Cys Gly Leu Glu Lys Gln Leu Lys Cys 
145                 150                 155     


<210>  14
<211>  129
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  truncated TetR lacking helix 1, 2, 3 and 4

<400>  14

Trp Gln Asp Phe Leu Arg Asn Asn Ala Lys Ser Phe Arg Cys Ala Leu 
1               5                   10                  15      


Leu Ser His Arg Asp Gly Ala Lys Val His Leu Gly Thr Arg Pro Thr 
            20                  25                  30          


Glu Lys Gln Tyr Glu Thr Leu Glu Asn Gln Leu Ala Phe Leu Cys Gln 
        35                  40                  45              


Gln Gly Phe Ser Leu Glu Asn Ala Leu Tyr Ala Leu Ser Ala Val Gly 
    50                  55                  60                  


His Phe Thr Leu Gly Cys Val Leu Glu Asp Gln Glu His Gln Val Ala 
65                  70                  75                  80  


Lys Glu Glu Arg Glu Thr Pro Thr Thr Asp Ser Met Pro Pro Leu Leu 
                85                  90                  95      


Arg Gln Ala Ile Glu Leu Phe Asp His Gln Gly Ala Glu Pro Ala Phe 
            100                 105                 110         


Leu Phe Gly Leu Glu Leu Ile Ile Cys Gly Leu Glu Lys Gln Leu Lys 
        115                 120                 125             


Cys 
    


<210>  15
<211>  75
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  truncated TetR comprising helix 8, 9 and 10

<400>  15

Leu Glu Asn Ala Leu Tyr Ala Leu Ser Ala Val Gly His Phe Thr Leu 
1               5                   10                  15      


Gly Cys Val Leu Glu Asp Gln Glu His Gln Val Ala Lys Glu Glu Arg 
            20                  25                  30          


Glu Thr Pro Thr Thr Asp Ser Met Pro Pro Leu Leu Arg Gln Ala Ile 
        35                  40                  45              


Glu Leu Phe Asp His Gln Gly Ala Glu Pro Ala Phe Leu Phe Gly Leu 
    50                  55                  60                  


Glu Leu Ile Ile Cys Gly Leu Glu Lys Gln Leu 
65                  70                  75  


<210>  16
<211>  61
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker (modified CD4 endodomain)

<400>  16

Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly 
1               5                   10                  15      


Leu Gly Ile Phe Phe Cys Val Arg Cys Arg His Arg Arg Arg Gln Ala 
            20                  25                  30          


Glu Arg Met Ala Gln Ile Lys Arg Val Val Ser Glu Lys Lys Thr Ala 
        35                  40                  45              


Gln Ala Pro His Arg Phe Gln Lys Thr Cys Ser Pro Ile 
    50                  55                  60      


<210>  17
<211>  202
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  wild-type TetR sequence

<400>  17

Ser Arg Leu Asp Lys Ser Lys Val Ile Asn Ser Ala Leu Glu Leu Leu 
1               5                   10                  15      


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


Leu Gly Val Glu Gln Pro Thr Leu Tyr Trp His Val Lys Asn Lys Arg 
        35                  40                  45              


Ala Leu Leu Asp Ala Leu Ala Ile Glu Met Leu Asp Arg His His Thr 
    50                  55                  60                  


His Phe Cys Pro Leu Glu Gly Glu Ser Trp Gln Asp Phe Leu Arg Asn 
65                  70                  75                  80  


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


Lys Val His Leu Gly Thr Arg Pro Thr Glu Lys Gln Tyr Glu Thr Leu 
            100                 105                 110         


Glu Asn Gln Leu Ala Phe Leu Cys Gln Gln Gly Phe Ser Leu Glu Asn 
        115                 120                 125             


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


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


Thr Thr Asp Ser Met Pro Pro Leu Leu Arg Gln Ala Ile Glu Leu Phe 
                165                 170                 175     


Asp His Gln Gly Ala Glu Pro Ala Phe Leu Phe Gly Leu Glu Leu Ile 
            180                 185                 190         


Ile Cys Gly Leu Glu Lys Gln Leu Lys Cys 
        195                 200         


<210>  18
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR interacting peptide (TiP) sequence

<400>  18

Met Trp Thr Trp Asn Ala Tyr Ala Phe Ala Ala Pro Ser Gly Gly Gly 
1               5                   10                  15      


Ser 
    


<210>  19
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD3 Z endodomain

<400>  19

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly 
1               5                   10                  15      


Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr 
            20                  25                  30          


Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys 
        35                  40                  45              


Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys 
    50                  55                  60                  


Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg 
65                  70                  75                  80  


Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala 
                85                  90                  95      


Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
            100                 105                 110         


<210>  20
<211>  152
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28 and CD3 Zeta endodomains

<400>  20

Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro 
1               5                   10                  15      


Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro 
            20                  25                  30          


Arg Asp Phe Ala Ala Tyr Arg Ser Arg Val Lys Phe Ser Arg Ser Ala 
        35                  40                  45              


Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn Glu Leu 
    50                  55                  60                  


Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg Arg Gly 
65                  70                  75                  80  


Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro Gln Glu 
                85                  90                  95      


Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala Tyr Ser 
            100                 105                 110         


Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His Asp Gly 
        115                 120                 125             


Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp Ala Leu 
    130                 135                 140                 


His Met Gln Ala Leu Pro Pro Arg 
145                 150         


<210>  21
<211>  188
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD28, OX40 and CD3 Zeta endodomains

<400>  21

Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr Pro 
1               5                   10                  15      


Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro Pro 
            20                  25                  30          


Arg Asp Phe Ala Ala Tyr Arg Ser Arg Asp Gln Arg Leu Pro Pro Asp 
        35                  40                  45              


Ala His Lys Pro Pro Gly Gly Gly Ser Phe Arg Thr Pro Ile Gln Glu 
    50                  55                  60                  


Glu Gln Ala Asp Ala His Ser Thr Leu Ala Lys Ile Arg Val Lys Phe 
65                  70                  75                  80  


Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu 
                85                  90                  95      


Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp 
            100                 105                 110         


Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys 
        115                 120                 125             


Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala 
    130                 135                 140                 


Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys 
145                 150                 155                 160 


Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr 
                165                 170                 175     


Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg 
            180                 185             


<210>  22
<211>  20
<212>  PRT
<213>  Foot-and-mouth disease virus

<400>  22

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


Asn Pro Gly Pro 
            20  


<210>  23
<211>  20
<212>  PRT
<213>  Foot-and-mouth disease virus

<400>  23

Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 
1               5                   10                  15      


Asn Pro Gly Pro 
            20  


<210>  24
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetR interacting peptide (TiP)

<400>  24

Trp Thr Trp Asn Ala Tyr Ala Phe Ala Ala Pro Ser Gly Gly Gly Ser 
1               5                   10                  15      


<210>  25
<211>  87
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  intracellular linker domain derived from CD4 (WT)

<400>  25

Leu Ser Asp Ser Gly Gln Val Leu Leu Glu Ser Asn Ile Lys Val Leu 
1               5                   10                  15      


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


Gly Val Ala Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe Phe Cys 
        35                  40                  45              


Val Arg Cys Arg His Arg Arg Arg Gln Ala Glu Arg Met Ser Gln Ile 
    50                  55                  60                  


Lys Arg Leu Leu Ser Glu Lys Lys Thr Cys Gln Cys Pro His Arg Phe 
65                  70                  75                  80  


Gln Lys Thr Cys Ser Pro Ile 
                85          


<210>  26
<211>  61
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD4 endodomain optimized for

<400>  26

Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly 
1               5                   10                  15      


Leu Gly Ile Phe Phe Cys Val Arg Cys Arg His Arg Arg Arg Gln Ala 
            20                  25                  30          


Glu Arg Met Ala Gln Ile Lys Arg Val Val Ser Glu Lys Lys Thr Ala 
        35                  40                  45              


Gln Ala Pro His Arg Phe Gln Lys Thr Cys Ser Pro Ile 
    50                  55                  60      


<210>  27
<211>  926
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TetCAR amino acid sequence

<400>  27

Met Trp Thr Trp Asn Ala Tyr Ala Phe Ala Ala Pro Ser Gly Gly Gly 
1               5                   10                  15      


Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly Gln Asn Gln Leu Tyr Asn 
            20                  25                  30          


Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp Val Leu Asp Lys Arg 
        35                  40                  45              


Arg Gly Arg Asp Pro Glu Met Gly Gly Lys Pro Arg Arg Lys Asn Pro 
    50                  55                  60                  


Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys Asp Lys Met Ala Glu Ala 
65                  70                  75                  80  


Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg Arg Arg Gly Lys Gly His 
                85                  90                  95      


Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp 
            100                 105                 110         


Ala Leu His Met Gln Ala Leu Pro Pro Arg Arg Ala Glu Gly Arg Gly 
        115                 120                 125             


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


Val Pro Thr Gln Val Leu Gly Leu Leu Leu Leu Trp Leu Thr Asp Ala 
145                 150                 155                 160 


Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser 
                165                 170                 175     


Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asp Ile Tyr 
            180                 185                 190         


Phe Asn Leu Val Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu 
        195                 200                 205             


Leu Ile Tyr Asp Thr Asn Arg Leu Ala Asp Gly Val Pro Ser Arg Phe 
    210                 215                 220                 


Ser Gly Ser Gly Ser Gly Thr Gln Tyr Thr Leu Thr Ile Ser Ser Leu 
225                 230                 235                 240 


Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Tyr Lys Asn Tyr 
                245                 250                 255     


Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Ser Gly 
            260                 265                 270         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        275                 280                 285             


Gly Gly Ser Arg Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu 
    290                 295                 300                 


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
305                 310                 315                 320 


Thr Leu Ser Asn Tyr Gly Met His Trp Ile Arg Gln Ala Pro Gly Lys 
                325                 330                 335     


Gly Leu Glu Trp Val Ser Ser Ile Ser Leu Asn Gly Gly Ser Thr Tyr 
            340                 345                 350         


Tyr Arg Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala 
        355                 360                 365             


Lys Ser Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
    370                 375                 380                 


Ala Val Tyr Tyr Cys Ala Ala Gln Asp Ala Tyr Thr Gly Gly Tyr Phe 
385                 390                 395                 400 


Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Met Asp Pro 
                405                 410                 415     


Ala Glu Pro Lys Ser Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
            420                 425                 430         


Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
        435                 440                 445             


Lys Asp Thr Leu Met Ile Ala Arg Thr Pro Glu Val Thr Cys Val Val 
    450                 455                 460                 


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
465                 470                 475                 480 


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
                485                 490                 495     


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
            500                 505                 510         


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
        515                 520                 525             


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
    530                 535                 540                 


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
545                 550                 555                 560 


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
                565                 570                 575     


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
            580                 585                 590         


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
        595                 600                 605             


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
    610                 615                 620                 


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
625                 630                 635                 640 


Ser Leu Ser Leu Ser Pro Gly Lys Lys Asp Pro Met Ala Leu Ile Val 
                645                 650                 655     


Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile Gly Leu Gly Ile Phe 
            660                 665                 670         


Phe Cys Val Arg Cys Arg His Arg Arg Arg Gln Ala Glu Arg Met Ala 
        675                 680                 685             


Gln Ile Lys Arg Val Val Ser Glu Lys Lys Thr Ala Gln Ala Pro His 
    690                 695                 700                 


Arg Phe Gln Lys Thr Cys Ser Pro Ile Ser Gly Gly Gly Gly Ser Met 
705                 710                 715                 720 


Ser Arg Leu Asp Lys Ser Lys Val Ile Asn Ser Ala Leu Glu Leu Leu 
                725                 730                 735     


Asn Glu Val Gly Ile Glu Gly Leu Thr Thr Arg Lys Leu Ala Gln Lys 
            740                 745                 750         


Leu Gly Val Glu Gln Pro Thr Leu Tyr Trp His Val Lys Asn Lys Arg 
        755                 760                 765             


Ala Leu Leu Asp Ala Leu Ala Ile Glu Met Leu Asp Arg His His Thr 
    770                 775                 780                 


His Phe Cys Pro Leu Glu Gly Glu Ser Trp Gln Asp Phe Leu Arg Asn 
785                 790                 795                 800 


Asn Ala Lys Ser Phe Arg Cys Ala Leu Leu Ser His Arg Asp Gly Ala 
                805                 810                 815     


Lys Val His Leu Gly Thr Arg Pro Thr Glu Lys Gln Tyr Glu Thr Leu 
            820                 825                 830         


Glu Asn Gln Leu Ala Phe Leu Cys Gln Gln Gly Phe Ser Leu Glu Asn 
        835                 840                 845             


Ala Leu Tyr Ala Leu Ser Ala Val Gly His Phe Thr Leu Gly Cys Val 
    850                 855                 860                 


Leu Glu Asp Gln Glu His Gln Val Ala Lys Glu Glu Arg Glu Thr Pro 
865                 870                 875                 880 


Thr Thr Asp Ser Met Pro Pro Leu Leu Arg Gln Ala Ile Glu Leu Phe 
                885                 890                 895     


Asp His Gln Gly Ala Glu Pro Ala Phe Leu Phe Gly Leu Glu Leu Ile 
            900                 905                 910         


Ile Cys Gly Leu Glu Lys Gln Leu Lys Cys Glu Ser Gly Ser 
        915                 920                 925     


