                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG, Basel (CH)
       Roche Diagnostics GmbH, Mannheim (DE)
 
<120>  Quantitative control of sialylation and specific mono-sialylation

<130>  31662 WO

<150>  EP13175347.7
<151>  2013-07-05

<160>  7     

<170>  PatentIn version 3.5

<210>  1
<211>  406
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<223>  hST6-Gal-I WT polypeptide

<400>  1

Met Ile His Thr Asn Leu Lys Lys Lys Phe Ser Cys Cys Val Leu Val 
1               5                   10                  15      


Phe Leu Leu Phe Ala Val Ile Cys Val Trp Lys Glu Lys Lys Lys Gly 
            20                  25                  30          


Ser Tyr Tyr Asp Ser Phe Lys Leu Gln Thr Lys Glu Phe Gln Val Leu 
        35                  40                  45              


Lys Ser Leu Gly Lys Leu Ala Met Gly Ser Asp Ser Gln Ser Val Ser 
    50                  55                  60                  


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


Leu Arg Gly Leu Ala Lys Ala Lys Pro Glu Ala Ser Phe Gln Val Trp 
                85                  90                  95      


Asn Lys Asp Ser Ser Ser Lys Asn Leu Ile Pro Arg Leu Gln Lys Ile 
            100                 105                 110         


Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr Lys Val Ser Tyr Lys Gly 
        115                 120                 125             


Pro Gly Pro Gly Ile Lys Phe Ser Ala Glu Ala Leu Arg Cys His Leu 
    130                 135                 140                 


Arg Asp His Val Asn Val Ser Met Val Glu Val Thr Asp Phe Pro Phe 
145                 150                 155                 160 


Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro Lys Glu Ser Ile Arg Thr 
                165                 170                 175     


Lys Ala Gly Pro Trp Gly Arg Cys Ala Val Val Ser Ser Ala Gly Ser 
            180                 185                 190         


Leu Lys Ser Ser Gln Leu Gly Arg Glu Ile Asp Asp His Asp Ala Val 
        195                 200                 205             


Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn Phe Gln Gln Asp Val Gly 
    210                 215                 220                 


Thr Lys Thr Thr Ile Arg Leu Met Asn Ser Gln Leu Val Thr Thr Glu 
225                 230                 235                 240 


Lys Arg Phe Leu Lys Asp Ser Leu Tyr Asn Glu Gly Ile Leu Ile Val 
                245                 250                 255     


Trp Asp Pro Ser Val Tyr His Ser Asp Ile Pro Lys Trp Tyr Gln Asn 
            260                 265                 270         


Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys Thr Tyr Arg Lys Leu His 
        275                 280                 285             


Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro Gln Met Pro Trp Glu Leu 
    290                 295                 300                 


Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu Glu Ile Gln Pro Asn Pro 
305                 310                 315                 320 


Pro Ser Ser Gly Met Leu Gly Ile Ile Ile Met Met Thr Leu Cys Asp 
                325                 330                 335     


Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser Lys Arg Lys Thr Asp Val 
            340                 345                 350         


Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser Ala Cys Thr Met Gly Ala 
        355                 360                 365             


Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu Val Lys His Leu Asn Gln 
    370                 375                 380                 


Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly Lys Ala Thr Leu Pro Gly 
385                 390                 395                 400 


Phe Arg Thr Ile His Cys 
                405     


<210>  2
<211>  317
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  delta89 truncation variant of hST6Gal-I

<400>  2

Glu Ala Ser Phe Gln Val Trp Asn Lys Asp Ser Ser Ser Lys Asn Leu 
1               5                   10                  15      


Ile Pro Arg Leu Gln Lys Ile Trp Lys Asn Tyr Leu Ser Met Asn Lys 
            20                  25                  30          


Tyr Lys Val Ser Tyr Lys Gly Pro Gly Pro Gly Ile Lys Phe Ser Ala 
        35                  40                  45              


Glu Ala Leu Arg Cys His Leu Arg Asp His Val Asn Val Ser Met Val 
    50                  55                  60                  


Glu Val Thr Asp Phe Pro Phe Asn Thr Ser Glu Trp Glu Gly Tyr Leu 
65                  70                  75                  80  


Pro Lys Glu Ser Ile Arg Thr Lys Ala Gly Pro Trp Gly Arg Cys Ala 
                85                  90                  95      


Val Val Ser Ser Ala Gly Ser Leu Lys Ser Ser Gln Leu Gly Arg Glu 
            100                 105                 110         


Ile Asp Asp His Asp Ala Val Leu Arg Phe Asn Gly Ala Pro Thr Ala 
        115                 120                 125             


Asn Phe Gln Gln Asp Val Gly Thr Lys Thr Thr Ile Arg Leu Met Asn 
    130                 135                 140                 


Ser Gln Leu Val Thr Thr Glu Lys Arg Phe Leu Lys Asp Ser Leu Tyr 
145                 150                 155                 160 


Asn Glu Gly Ile Leu Ile Val Trp Asp Pro Ser Val Tyr His Ser Asp 
                165                 170                 175     


Ile Pro Lys Trp Tyr Gln Asn Pro Asp Tyr Asn Phe Phe Asn Asn Tyr 
            180                 185                 190         


Lys Thr Tyr Arg Lys Leu His Pro Asn Gln Pro Phe Tyr Ile Leu Lys 
        195                 200                 205             


Pro Gln Met Pro Trp Glu Leu Trp Asp Ile Leu Gln Glu Ile Ser Pro 
    210                 215                 220                 


Glu Glu Ile Gln Pro Asn Pro Pro Ser Ser Gly Met Leu Gly Ile Ile 
225                 230                 235                 240 


Ile Met Met Thr Leu Cys Asp Gln Val Asp Ile Tyr Glu Phe Leu Pro 
                245                 250                 255     


Ser Lys Arg Lys Thr Asp Val Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp 
            260                 265                 270         


Ser Ala Cys Thr Met Gly Ala Tyr His Pro Leu Leu Tyr Glu Lys Asn 
        275                 280                 285             


Leu Val Lys His Leu Asn Gln Gly Thr Asp Glu Asp Ile Tyr Leu Leu 
    290                 295                 300                 


Gly Lys Ala Thr Leu Pro Gly Phe Arg Thr Ile His Cys 
305                 310                 315         


<210>  3
<211>  298
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  delta108 truncation variant of hST6Gal-I

<400>  3

Leu Gln Lys Ile Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr Lys Val 
1               5                   10                  15      


Ser Tyr Lys Gly Pro Gly Pro Gly Ile Lys Phe Ser Ala Glu Ala Leu 
            20                  25                  30          


Arg Cys His Leu Arg Asp His Val Asn Val Ser Met Val Glu Val Thr 
        35                  40                  45              


Asp Phe Pro Phe Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro Lys Glu 
    50                  55                  60                  


Ser Ile Arg Thr Lys Ala Gly Pro Trp Gly Arg Cys Ala Val Val Ser 
65                  70                  75                  80  


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


His Asp Ala Val Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn Phe Gln 
            100                 105                 110         


Gln Asp Val Gly Thr Lys Thr Thr Ile Arg Leu Met Asn Ser Gln Leu 
        115                 120                 125             


Val Thr Thr Glu Lys Arg Phe Leu Lys Asp Ser Leu Tyr Asn Glu Gly 
    130                 135                 140                 


Ile Leu Ile Val Trp Asp Pro Ser Val Tyr His Ser Asp Ile Pro Lys 
145                 150                 155                 160 


Trp Tyr Gln Asn Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys Thr Tyr 
                165                 170                 175     


Arg Lys Leu His Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro Gln Met 
            180                 185                 190         


Pro Trp Glu Leu Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu Glu Ile 
        195                 200                 205             


Gln Pro Asn Pro Pro Ser Ser Gly Met Leu Gly Ile Ile Ile Met Met 
    210                 215                 220                 


Thr Leu Cys Asp Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser Lys Arg 
225                 230                 235                 240 


Lys Thr Asp Val Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser Ala Cys 
                245                 250                 255     


Thr Met Gly Ala Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu Val Lys 
            260                 265                 270         


His Leu Asn Gln Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly Lys Ala 
        275                 280                 285             


Thr Leu Pro Gly Phe Arg Thr Ile His Cys 
    290                 295             


<210>  4
<211>  1054
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Expression construct Epo-AP-delta89 ST6 (encoded amino acids of 
       positions 90-406 of hST6Gal-I wild-type protein if SEQ ID NO:1, 
       N-terminal methionine added)


<220>
<221>  CDS
<222>  (8)..(1048)
<223>  open reading frame

<400>  4
gtcgacc atg ggc gtg cac gaa tgt cct gcc tgg ctg tgg ctg ctg ctg         49
        Met Gly Val His Glu Cys Pro Ala Trp Leu Trp Leu Leu Leu           
        1               5                   10                            

agc ctg ctg tct ctg cct ctg gga ctg cct gtg ctg ggc gcc cct gaa         97
Ser Leu Leu Ser Leu Pro Leu Gly Leu Pro Val Leu Gly Ala Pro Glu           
15                  20                  25                  30            

gcc tct ttc cag gtg tgg aac aag gac agc agc tcc aag aac ctg atc        145
Ala Ser Phe Gln Val Trp Asn Lys Asp Ser Ser Ser Lys Asn Leu Ile           
                35                  40                  45                

ccc cgg ctg cag aag atc tgg aag aac tac ctg agc atg aac aag tac        193
Pro Arg Leu Gln Lys Ile Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr           
            50                  55                  60                    

aag gtg tcc tac aag ggc cct ggc cct ggc atc aag ttt agc gcc gag        241
Lys Val Ser Tyr Lys Gly Pro Gly Pro Gly Ile Lys Phe Ser Ala Glu           
        65                  70                  75                        

gcc ctg aga tgc cac ctg agg gat cac gtg aac gtg tcc atg gtg gaa        289
Ala Leu Arg Cys His Leu Arg Asp His Val Asn Val Ser Met Val Glu           
    80                  85                  90                            

gtg acc gac ttc cca ttc aac acc agc gag tgg gag ggc tac ctg ccc        337
Val Thr Asp Phe Pro Phe Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro           
95                  100                 105                 110           

aaa gag agc atc cgg acc aaa gcc ggc cct tgg gga aga tgt gcc gtg        385
Lys Glu Ser Ile Arg Thr Lys Ala Gly Pro Trp Gly Arg Cys Ala Val           
                115                 120                 125               

gtg tct agc gcc ggc agc ctg aag agt agc cag ctg ggc aga gag atc        433
Val Ser Ser Ala Gly Ser Leu Lys Ser Ser Gln Leu Gly Arg Glu Ile           
            130                 135                 140                   

gac gac cac gac gcc gtg ctg cgg ttc aat ggc gct ccc acc gcc aac        481
Asp Asp His Asp Ala Val Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn           
        145                 150                 155                       

ttc cag cag gac gtg ggc acc aag acc acc atc cgg ctg atg aac tcc        529
Phe Gln Gln Asp Val Gly Thr Lys Thr Thr Ile Arg Leu Met Asn Ser           
    160                 165                 170                           

cag ctc gtg aca acc gag aag cgg ttc ctg aag gac agc ctg tac aac        577
Gln Leu Val Thr Thr Glu Lys Arg Phe Leu Lys Asp Ser Leu Tyr Asn           
175                 180                 185                 190           

gag ggc atc ctg atc gtg tgg gac ccc agc gtg tac cac agc gac atc        625
Glu Gly Ile Leu Ile Val Trp Asp Pro Ser Val Tyr His Ser Asp Ile           
                195                 200                 205               

ccc aag tgg tat cag aac ccc gac tac aac ttc ttc aac aac tac aag        673
Pro Lys Trp Tyr Gln Asn Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys           
            210                 215                 220                   

acc tac cgg aag ctg cac ccc aac cag ccc ttc tac atc ctg aag ccc        721
Thr Tyr Arg Lys Leu His Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro           
        225                 230                 235                       

cag atg ccc tgg gag ctg tgg gac att ctg cag gaa atc agc ccc gaa        769
Gln Met Pro Trp Glu Leu Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu           
    240                 245                 250                           

gag atc cag ccc aac ccc cct agc tct ggc atg ctg ggc atc att atc        817
Glu Ile Gln Pro Asn Pro Pro Ser Ser Gly Met Leu Gly Ile Ile Ile           
255                 260                 265                 270           

atg atg acc ctg tgc gac cag gtg gac atc tac gag ttt ctg ccc tcc        865
Met Met Thr Leu Cys Asp Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser           
                275                 280                 285               

aag aga aag acc gac gtg tgc tac tac tac cag aag ttc ttc gac agc        913
Lys Arg Lys Thr Asp Val Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser           
            290                 295                 300                   

gcc tgc acc atg gga gcc tac cac cct ctg ctg tac gag aag aac ctc        961
Ala Cys Thr Met Gly Ala Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu           
        305                 310                 315                       

gtg aag cac ctg aac cag ggc acc gac gag gat atc tac ctg ctg ggc       1009
Val Lys His Leu Asn Gln Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly           
    320                 325                 330                           

aag gcc acc ctg ccc ggc ttc aga acc atc cac tgc tga ggatcc            1054
Lys Ala Thr Leu Pro Gly Phe Arg Thr Ile His Cys                           
335                 340                 345                               


<210>  5
<211>  346
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  5

Met Gly Val His Glu Cys Pro Ala Trp Leu Trp Leu Leu Leu Ser Leu 
1               5                   10                  15      


Leu Ser Leu Pro Leu Gly Leu Pro Val Leu Gly Ala Pro Glu Ala Ser 
            20                  25                  30          


Phe Gln Val Trp Asn Lys Asp Ser Ser Ser Lys Asn Leu Ile Pro Arg 
        35                  40                  45              


Leu Gln Lys Ile Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr Lys Val 
    50                  55                  60                  


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


Arg Cys His Leu Arg Asp His Val Asn Val Ser Met Val Glu Val Thr 
                85                  90                  95      


Asp Phe Pro Phe Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro Lys Glu 
            100                 105                 110         


Ser Ile Arg Thr Lys Ala Gly Pro Trp Gly Arg Cys Ala Val Val Ser 
        115                 120                 125             


Ser Ala Gly Ser Leu Lys Ser Ser Gln Leu Gly Arg Glu Ile Asp Asp 
    130                 135                 140                 


His Asp Ala Val Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn Phe Gln 
145                 150                 155                 160 


Gln Asp Val Gly Thr Lys Thr Thr Ile Arg Leu Met Asn Ser Gln Leu 
                165                 170                 175     


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


Ile Leu Ile Val Trp Asp Pro Ser Val Tyr His Ser Asp Ile Pro Lys 
        195                 200                 205             


Trp Tyr Gln Asn Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys Thr Tyr 
    210                 215                 220                 


Arg Lys Leu His Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro Gln Met 
225                 230                 235                 240 


Pro Trp Glu Leu Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu Glu Ile 
                245                 250                 255     


Gln Pro Asn Pro Pro Ser Ser Gly Met Leu Gly Ile Ile Ile Met Met 
            260                 265                 270         


Thr Leu Cys Asp Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser Lys Arg 
        275                 280                 285             


Lys Thr Asp Val Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser Ala Cys 
    290                 295                 300                 


Thr Met Gly Ala Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu Val Lys 
305                 310                 315                 320 


His Leu Asn Gln Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly Lys Ala 
                325                 330                 335     


Thr Leu Pro Gly Phe Arg Thr Ile His Cys 
            340                 345     


<210>  6
<211>  1003
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Expression construct Epo-AP-delta108 ST6 (encoded amino acids of 
       positions 109-406 of hST6Gal-I wild-type protein if SEQ ID NO:1, 
       N-terminal methionine added)


<220>
<221>  CDS
<222>  (8)..(997)
<223>  open reading frame

<400>  6
gtcgacc atg ggc gtg cac gaa tgt cct gcc tgg ctg tgg ctg ctg ctg         49
        Met Gly Val His Glu Cys Pro Ala Trp Leu Trp Leu Leu Leu           
        1               5                   10                            

agc ctg ctg tct ctg cct ctg gga ctg cct gtg ctg ggc gcc cct cct         97
Ser Leu Leu Ser Leu Pro Leu Gly Leu Pro Val Leu Gly Ala Pro Pro           
15                  20                  25                  30            

aga ctg cag aag atc tgg aag aac tac ctg agc atg aac aag tac aag        145
Arg Leu Gln Lys Ile Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr Lys           
                35                  40                  45                

gtg tcc tac aag ggc cct ggc cct ggc atc aag ttt agc gcc gag gcc        193
Val Ser Tyr Lys Gly Pro Gly Pro Gly Ile Lys Phe Ser Ala Glu Ala           
            50                  55                  60                    

ctg aga tgc cac ctg agg gat cac gtg aac gtg tcc atg gtg gaa gtg        241
Leu Arg Cys His Leu Arg Asp His Val Asn Val Ser Met Val Glu Val           
        65                  70                  75                        

acc gac ttc cca ttc aac acc agc gag tgg gag ggc tac ctg ccc aaa        289
Thr Asp Phe Pro Phe Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro Lys           
    80                  85                  90                            

gag agc atc cgg acc aaa gcc ggc cct tgg gga aga tgt gcc gtg gtg        337
Glu Ser Ile Arg Thr Lys Ala Gly Pro Trp Gly Arg Cys Ala Val Val           
95                  100                 105                 110           

tct agc gcc ggc agc ctg aag agt agc cag ctg ggc aga gag atc gac        385
Ser Ser Ala Gly Ser Leu Lys Ser Ser Gln Leu Gly Arg Glu Ile Asp           
                115                 120                 125               

gac cac gac gcc gtg ctg cgg ttc aat ggc gct ccc acc gcc aac ttc        433
Asp His Asp Ala Val Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn Phe           
            130                 135                 140                   

cag cag gac gtg ggc acc aag acc acc atc cgg ctg atg aac tcc cag        481
Gln Gln Asp Val Gly Thr Lys Thr Thr Ile Arg Leu Met Asn Ser Gln           
        145                 150                 155                       

ctc gtg aca acc gag aag cgg ttc ctg aag gac agc ctg tac aac gag        529
Leu Val Thr Thr Glu Lys Arg Phe Leu Lys Asp Ser Leu Tyr Asn Glu           
    160                 165                 170                           

ggc atc ctg atc gtg tgg gac ccc agc gtg tac cac agc gac atc ccc        577
Gly Ile Leu Ile Val Trp Asp Pro Ser Val Tyr His Ser Asp Ile Pro           
175                 180                 185                 190           

aag tgg tat cag aac ccc gac tac aac ttc ttc aac aac tac aag acc        625
Lys Trp Tyr Gln Asn Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys Thr           
                195                 200                 205               

tac cgg aag ctg cac ccc aac cag ccc ttc tac atc ctg aag ccc cag        673
Tyr Arg Lys Leu His Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro Gln           
            210                 215                 220                   

atg ccc tgg gag ctg tgg gac att ctg cag gaa atc agc ccc gaa gag        721
Met Pro Trp Glu Leu Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu Glu           
        225                 230                 235                       

atc cag ccc aac ccc cct agc tct ggc atg ctg ggc atc att atc atg        769
Ile Gln Pro Asn Pro Pro Ser Ser Gly Met Leu Gly Ile Ile Ile Met           
    240                 245                 250                           

atg acc ctg tgc gac cag gtg gac atc tac gag ttt ctg ccc tcc aag        817
Met Thr Leu Cys Asp Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser Lys           
255                 260                 265                 270           

aga aag acc gac gtg tgc tac tac tac cag aag ttc ttc gac agc gcc        865
Arg Lys Thr Asp Val Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser Ala           
                275                 280                 285               

tgc acc atg gga gcc tac cac cct ctg ctg tac gag aag aac ctc gtg        913
Cys Thr Met Gly Ala Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu Val           
            290                 295                 300                   

aag cac ctg aac cag ggc acc gac gag gat atc tac ctg ctg ggc aag        961
Lys His Leu Asn Gln Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly Lys           
        305                 310                 315                       

gcc acc ctg ccc ggc ttc aga acc atc cac tgc tga ggatcc                1003
Ala Thr Leu Pro Gly Phe Arg Thr Ile His Cys                               
    320                 325                                               


<210>  7
<211>  329
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  7

Met Gly Val His Glu Cys Pro Ala Trp Leu Trp Leu Leu Leu Ser Leu 
1               5                   10                  15      


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


Gln Lys Ile Trp Lys Asn Tyr Leu Ser Met Asn Lys Tyr Lys Val Ser 
        35                  40                  45              


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


Cys His Leu Arg Asp His Val Asn Val Ser Met Val Glu Val Thr Asp 
65                  70                  75                  80  


Phe Pro Phe Asn Thr Ser Glu Trp Glu Gly Tyr Leu Pro Lys Glu Ser 
                85                  90                  95      


Ile Arg Thr Lys Ala Gly Pro Trp Gly Arg Cys Ala Val Val Ser Ser 
            100                 105                 110         


Ala Gly Ser Leu Lys Ser Ser Gln Leu Gly Arg Glu Ile Asp Asp His 
        115                 120                 125             


Asp Ala Val Leu Arg Phe Asn Gly Ala Pro Thr Ala Asn Phe Gln Gln 
    130                 135                 140                 


Asp Val Gly Thr Lys Thr Thr Ile Arg Leu Met Asn Ser Gln Leu Val 
145                 150                 155                 160 


Thr Thr Glu Lys Arg Phe Leu Lys Asp Ser Leu Tyr Asn Glu Gly Ile 
                165                 170                 175     


Leu Ile Val Trp Asp Pro Ser Val Tyr His Ser Asp Ile Pro Lys Trp 
            180                 185                 190         


Tyr Gln Asn Pro Asp Tyr Asn Phe Phe Asn Asn Tyr Lys Thr Tyr Arg 
        195                 200                 205             


Lys Leu His Pro Asn Gln Pro Phe Tyr Ile Leu Lys Pro Gln Met Pro 
    210                 215                 220                 


Trp Glu Leu Trp Asp Ile Leu Gln Glu Ile Ser Pro Glu Glu Ile Gln 
225                 230                 235                 240 


Pro Asn Pro Pro Ser Ser Gly Met Leu Gly Ile Ile Ile Met Met Thr 
                245                 250                 255     


Leu Cys Asp Gln Val Asp Ile Tyr Glu Phe Leu Pro Ser Lys Arg Lys 
            260                 265                 270         


Thr Asp Val Cys Tyr Tyr Tyr Gln Lys Phe Phe Asp Ser Ala Cys Thr 
        275                 280                 285             


Met Gly Ala Tyr His Pro Leu Leu Tyr Glu Lys Asn Leu Val Lys His 
    290                 295                 300                 


Leu Asn Gln Gly Thr Asp Glu Asp Ile Tyr Leu Leu Gly Lys Ala Thr 
305                 310                 315                 320 


Leu Pro Gly Phe Arg Thr Ile His Cys 
                325                 


