                         SEQUENCE LISTING

<110>  Genzyme Corporation
 
<120>  PHARMACEUTICAL COMPOSITIONS FOR TREATING ACID SPHINGOMYELINASE 
       DEFICIENCY

<130>  022548.WO048

<150>  62/676,525
<151>  2018-05-25

<160>  6     

<170>  PatentIn version 3.5

<210>  1
<211>  627
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Arg Tyr Gly Ala Ser Leu Arg Gln Ser Cys Pro Arg Ser Gly 
1               5                   10                  15      


Arg Glu Gln Gly Gln Asp Gly Thr Ala Gly Ala Pro Gly Leu Leu Trp 
            20                  25                  30          


Met Gly Leu Ala Leu Ala Leu Ala Leu Ala Leu Ala Leu Ser Asp Ser 
        35                  40                  45              


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


His Pro Ala Arg Leu His Arg Ile Val Pro Arg Leu Arg Asp Val Phe 
65                  70                  75                  80  


Gly Trp Gly Asn Leu Thr Cys Pro Ile Cys Lys Gly Leu Phe Thr Ala 
                85                  90                  95      


Ile Asn Leu Gly Leu Lys Lys Glu Pro Asn Val Ala Arg Val Gly Ser 
            100                 105                 110         


Val Ala Ile Lys Leu Cys Asn Leu Leu Lys Ile Ala Pro Pro Ala Val 
        115                 120                 125             


Cys Gln Ser Ile Val His Leu Phe Glu Asp Asp Met Val Glu Val Trp 
    130                 135                 140                 


Arg Arg Ser Val Leu Ser Pro Ser Glu Ala Cys Gly Leu Leu Leu Gly 
145                 150                 155                 160 


Ser Thr Cys Gly His Trp Asp Ile Phe Ser Ser Trp Asn Ile Ser Leu 
                165                 170                 175     


Pro Thr Val Pro Lys Pro Pro Pro Lys Pro Pro Ser Pro Pro Ala Pro 
            180                 185                 190         


Gly Ala Pro Val Ser Arg Ile Leu Phe Leu Thr Asp Leu His Trp Asp 
        195                 200                 205             


His Asp Tyr Leu Glu Gly Thr Asp Pro Asp Cys Ala Asp Pro Leu Cys 
    210                 215                 220                 


Cys Arg Arg Gly Ser Gly Leu Pro Pro Ala Ser Arg Pro Gly Ala Gly 
225                 230                 235                 240 


Tyr Trp Gly Glu Tyr Ser Lys Cys Asp Leu Pro Leu Arg Thr Leu Glu 
                245                 250                 255     


Ser Leu Leu Ser Gly Leu Gly Pro Ala Gly Pro Phe Asp Met Val Tyr 
            260                 265                 270         


Trp Thr Gly Asp Ile Pro Ala His Asp Val Trp His Gln Thr Arg Gln 
        275                 280                 285             


Asp Gln Leu Arg Ala Leu Thr Thr Val Thr Ala Leu Val Arg Lys Phe 
    290                 295                 300                 


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


Pro Val Asn Ser Phe Pro Pro Pro Phe Ile Glu Gly Asn His Ser Ser 
                325                 330                 335     


Arg Trp Leu Tyr Glu Ala Met Ala Lys Ala Trp Glu Pro Trp Leu Pro 
            340                 345                 350         


Ala Glu Ala Leu Arg Thr Leu Arg Ile Gly Gly Phe Tyr Ala Leu Ser 
        355                 360                 365             


Pro Tyr Pro Gly Leu Arg Leu Ile Ser Leu Asn Met Asn Phe Cys Ser 
    370                 375                 380                 


Arg Glu Asn Phe Trp Leu Leu Ile Asn Ser Thr Asp Pro Ala Gly Gln 
385                 390                 395                 400 


Leu Gln Trp Leu Val Gly Glu Leu Gln Ala Ala Glu Asp Arg Gly Asp 
                405                 410                 415     


Lys Val His Ile Ile Gly His Ile Pro Pro Gly His Cys Leu Lys Ser 
            420                 425                 430         


Trp Ser Trp Asn Tyr Tyr Arg Ile Val Ala Arg Tyr Glu Asn Thr Leu 
        435                 440                 445             


Ala Ala Gln Phe Phe Gly His Thr His Val Asp Glu Phe Glu Val Phe 
    450                 455                 460                 


Tyr Asp Glu Glu Thr Leu Ser Arg Pro Leu Ala Val Ala Phe Leu Ala 
465                 470                 475                 480 


Pro Ser Ala Thr Thr Tyr Ile Gly Leu Asn Pro Gly Tyr Arg Val Tyr 
                485                 490                 495     


Gln Ile Asp Gly Asn Tyr Ser Gly Ser Ser His Val Val Leu Asp His 
            500                 505                 510         


Glu Thr Tyr Ile Leu Asn Leu Thr Gln Ala Asn Ile Pro Gly Ala Ile 
        515                 520                 525             


Pro His Trp Gln Leu Leu Tyr Arg Ala Arg Glu Thr Tyr Gly Leu Pro 
    530                 535                 540                 


Asn Thr Leu Pro Thr Ala Trp His Asn Leu Val Tyr Arg Met Arg Gly 
545                 550                 555                 560 


Asp Met Gln Leu Phe Gln Thr Phe Trp Phe Leu Tyr His Lys Gly His 
                565                 570                 575     


Pro Pro Ser Glu Pro Cys Gly Thr Pro Cys Arg Leu Ala Thr Leu Cys 
            580                 585                 590         


Ala Gln Leu Ser Ala Arg Ala Asp Ser Pro Ala Leu Cys Arg His Leu 
        595                 600                 605             


Met Pro Asp Gly Ser Leu Pro Glu Ala Gln Ser Leu Trp Pro Arg Pro 
    610                 615                 620                 


Leu Phe Cys 
625         


<210>  2
<211>  570
<212>  PRT
<213>  Homo sapiens

<400>  2

His Pro Leu Ser Pro Gln Gly His Pro Ala Arg Leu His Arg Ile Val 
1               5                   10                  15      


Pro Arg Leu Arg Asp Val Phe Gly Trp Gly Asn Leu Thr Cys Pro Ile 
            20                  25                  30          


Cys Lys Gly Leu Phe Thr Ala Ile Asn Leu Gly Leu Lys Lys Glu Pro 
        35                  40                  45              


Asn Val Ala Arg Val Gly Ser Val Ala Ile Lys Leu Cys Asn Leu Leu 
    50                  55                  60                  


Lys Ile Ala Pro Pro Ala Val Cys Gln Ser Ile Val His Leu Phe Glu 
65                  70                  75                  80  


Asp Asp Met Val Glu Val Trp Arg Arg Ser Val Leu Ser Pro Ser Glu 
                85                  90                  95      


Ala Cys Gly Leu Leu Leu Gly Ser Thr Cys Gly His Trp Asp Ile Phe 
            100                 105                 110         


Ser Ser Trp Asn Ile Ser Leu Pro Thr Val Pro Lys Pro Pro Pro Lys 
        115                 120                 125             


Pro Pro Ser Pro Pro Ala Pro Gly Ala Pro Val Ser Arg Ile Leu Phe 
    130                 135                 140                 


Leu Thr Asp Leu His Trp Asp His Asp Tyr Leu Glu Gly Thr Asp Pro 
145                 150                 155                 160 


Asp Cys Ala Asp Pro Leu Cys Cys Arg Arg Gly Ser Gly Leu Pro Pro 
                165                 170                 175     


Ala Ser Arg Pro Gly Ala Gly Tyr Trp Gly Glu Tyr Ser Lys Cys Asp 
            180                 185                 190         


Leu Pro Leu Arg Thr Leu Glu Ser Leu Leu Ser Gly Leu Gly Pro Ala 
        195                 200                 205             


Gly Pro Phe Asp Met Val Tyr Trp Thr Gly Asp Ile Pro Ala His Asp 
    210                 215                 220                 


Val Trp His Gln Thr Arg Gln Asp Gln Leu Arg Ala Leu Thr Thr Val 
225                 230                 235                 240 


Thr Ala Leu Val Arg Lys Phe Leu Gly Pro Val Pro Val Tyr Pro Ala 
                245                 250                 255     


Val Gly Asn His Glu Ser Thr Pro Val Asn Ser Phe Pro Pro Pro Phe 
            260                 265                 270         


Ile Glu Gly Asn His Ser Ser Arg Trp Leu Tyr Glu Ala Met Ala Lys 
        275                 280                 285             


Ala Trp Glu Pro Trp Leu Pro Ala Glu Ala Leu Arg Thr Leu Arg Ile 
    290                 295                 300                 


Gly Gly Phe Tyr Ala Leu Ser Pro Tyr Pro Gly Leu Arg Leu Ile Ser 
305                 310                 315                 320 


Leu Asn Met Asn Phe Cys Ser Arg Glu Asn Phe Trp Leu Leu Ile Asn 
                325                 330                 335     


Ser Thr Asp Pro Ala Gly Gln Leu Gln Trp Leu Val Gly Glu Leu Gln 
            340                 345                 350         


Ala Ala Glu Asp Arg Gly Asp Lys Val His Ile Ile Gly His Ile Pro 
        355                 360                 365             


Pro Gly His Cys Leu Lys Ser Trp Ser Trp Asn Tyr Tyr Arg Ile Val 
    370                 375                 380                 


Ala Arg Tyr Glu Asn Thr Leu Ala Ala Gln Phe Phe Gly His Thr His 
385                 390                 395                 400 


Val Asp Glu Phe Glu Val Phe Tyr Asp Glu Glu Thr Leu Ser Arg Pro 
                405                 410                 415     


Leu Ala Val Ala Phe Leu Ala Pro Ser Ala Thr Thr Tyr Ile Gly Leu 
            420                 425                 430         


Asn Pro Gly Tyr Arg Val Tyr Gln Ile Asp Gly Asn Tyr Ser Gly Ser 
        435                 440                 445             


Ser His Val Val Leu Asp His Glu Thr Tyr Ile Leu Asn Leu Thr Gln 
    450                 455                 460                 


Ala Asn Ile Pro Gly Ala Ile Pro His Trp Gln Leu Leu Tyr Arg Ala 
465                 470                 475                 480 


Arg Glu Thr Tyr Gly Leu Pro Asn Thr Leu Pro Thr Ala Trp His Asn 
                485                 490                 495     


Leu Val Tyr Arg Met Arg Gly Asp Met Gln Leu Phe Gln Thr Phe Trp 
            500                 505                 510         


Phe Leu Tyr His Lys Gly His Pro Pro Ser Glu Pro Cys Gly Thr Pro 
        515                 520                 525             


Cys Arg Leu Ala Thr Leu Cys Ala Gln Leu Ser Ala Arg Ala Asp Ser 
    530                 535                 540                 


Pro Ala Leu Cys Arg His Leu Met Pro Asp Gly Ser Leu Pro Glu Ala 
545                 550                 555                 560 


Gln Ser Leu Trp Pro Arg Pro Leu Phe Cys 
                565                 570 


<210>  3
<211>  629
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Pro Arg Tyr Gly Ala Ser Leu Arg Gln Ser Cys Pro Arg Ser Gly 
1               5                   10                  15      


Arg Glu Gln Gly Gln Asp Gly Thr Ala Gly Ala Pro Gly Leu Leu Trp 
            20                  25                  30          


Met Gly Leu Val Leu Ala Leu Ala Leu Ala Leu Ala Leu Ala Leu Ser 
        35                  40                  45              


Asp Ser Arg Val Leu Trp Ala Pro Ala Glu Ala His Pro Leu Ser Pro 
    50                  55                  60                  


Gln Gly His Pro Ala Arg Leu His Arg Ile Val Pro Arg Leu Arg Asp 
65                  70                  75                  80  


Val Phe Gly Trp Gly Asn Leu Thr Cys Pro Ile Cys Lys Gly Leu Phe 
                85                  90                  95      


Thr Ala Ile Asn Leu Gly Leu Lys Lys Glu Pro Asn Val Ala Arg Val 
            100                 105                 110         


Gly Ser Val Ala Ile Lys Leu Cys Asn Leu Leu Lys Ile Ala Pro Pro 
        115                 120                 125             


Ala Val Cys Gln Ser Ile Val His Leu Phe Glu Asp Asp Met Val Glu 
    130                 135                 140                 


Val Trp Arg Arg Ser Val Leu Ser Pro Ser Glu Ala Cys Gly Leu Leu 
145                 150                 155                 160 


Leu Gly Ser Thr Cys Gly His Trp Asp Ile Phe Ser Ser Trp Asn Ile 
                165                 170                 175     


Ser Leu Pro Thr Val Pro Lys Pro Pro Pro Lys Pro Pro Ser Pro Pro 
            180                 185                 190         


Ala Pro Gly Ala Pro Val Ser Arg Ile Leu Phe Leu Thr Asp Leu His 
        195                 200                 205             


Trp Asp His Asp Tyr Leu Glu Gly Thr Asp Pro Asp Cys Ala Asp Pro 
    210                 215                 220                 


Leu Cys Cys Arg Arg Gly Ser Gly Leu Pro Pro Ala Ser Arg Pro Gly 
225                 230                 235                 240 


Ala Gly Tyr Trp Gly Glu Tyr Ser Lys Cys Asp Leu Pro Leu Arg Thr 
                245                 250                 255     


Leu Glu Ser Leu Leu Ser Gly Leu Gly Pro Ala Gly Pro Phe Asp Met 
            260                 265                 270         


Val Tyr Trp Thr Gly Asp Ile Pro Ala His Asp Val Trp His Gln Thr 
        275                 280                 285             


Arg Gln Asp Gln Leu Arg Ala Leu Thr Thr Val Thr Ala Leu Val Arg 
    290                 295                 300                 


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


Ser Ile Pro Val Asn Ser Phe Pro Pro Pro Phe Ile Glu Gly Asn His 
                325                 330                 335     


Ser Ser Arg Trp Leu Tyr Glu Ala Met Ala Lys Ala Trp Glu Pro Trp 
            340                 345                 350         


Leu Pro Ala Glu Ala Leu Arg Thr Leu Arg Ile Gly Gly Phe Tyr Ala 
        355                 360                 365             


Leu Ser Pro Tyr Pro Gly Leu Arg Leu Ile Ser Leu Asn Met Asn Phe 
    370                 375                 380                 


Cys Ser Arg Glu Asn Phe Trp Leu Leu Ile Asn Ser Thr Asp Pro Ala 
385                 390                 395                 400 


Gly Gln Leu Gln Trp Leu Val Gly Glu Leu Gln Ala Ala Glu Asp Arg 
                405                 410                 415     


Gly Asp Lys Val His Ile Ile Gly His Ile Pro Pro Gly His Cys Leu 
            420                 425                 430         


Lys Ser Trp Ser Trp Asn Tyr Tyr Arg Ile Val Ala Arg Tyr Glu Asn 
        435                 440                 445             


Thr Leu Ala Ala Gln Phe Phe Gly His Thr His Val Asp Glu Phe Glu 
    450                 455                 460                 


Val Phe Tyr Asp Glu Glu Thr Leu Ser Arg Pro Leu Ala Val Ala Phe 
465                 470                 475                 480 


Leu Ala Pro Ser Ala Thr Thr Tyr Ile Gly Leu Asn Pro Gly Tyr Arg 
                485                 490                 495     


Val Tyr Gln Ile Asp Gly Asn Tyr Ser Arg Ser Ser His Val Val Leu 
            500                 505                 510         


Asp His Glu Thr Tyr Ile Leu Asn Leu Thr Gln Ala Asn Ile Pro Gly 
        515                 520                 525             


Ala Ile Pro His Trp Gln Leu Leu Tyr Arg Ala Arg Glu Thr Tyr Gly 
    530                 535                 540                 


Leu Pro Asn Thr Leu Pro Thr Ala Trp His Asn Leu Val Tyr Arg Met 
545                 550                 555                 560 


Arg Gly Asp Met Gln Leu Phe Gln Thr Phe Trp Phe Leu Tyr His Lys 
                565                 570                 575     


Gly His Pro Pro Ser Glu Pro Cys Gly Thr Pro Cys Arg Leu Ala Thr 
            580                 585                 590         


Leu Cys Ala Gln Leu Ser Ala Arg Ala Asp Ser Pro Ala Leu Cys Arg 
        595                 600                 605             


His Leu Met Pro Asp Gly Ser Leu Pro Glu Ala Gln Ser Leu Trp Pro 
    610                 615                 620                 


Arg Pro Leu Phe Cys 
625                 


<210>  4
<211>  570
<212>  PRT
<213>  Homo sapiens

<400>  4

His Pro Leu Ser Pro Gln Gly His Pro Ala Arg Leu His Arg Ile Val 
1               5                   10                  15      


Pro Arg Leu Arg Asp Val Phe Gly Trp Gly Asn Leu Thr Cys Pro Ile 
            20                  25                  30          


Cys Lys Gly Leu Phe Thr Ala Ile Asn Leu Gly Leu Lys Lys Glu Pro 
        35                  40                  45              


Asn Val Ala Arg Val Gly Ser Val Ala Ile Lys Leu Cys Asn Leu Leu 
    50                  55                  60                  


Lys Ile Ala Pro Pro Ala Val Cys Gln Ser Ile Val His Leu Phe Glu 
65                  70                  75                  80  


Asp Asp Met Val Glu Val Trp Arg Arg Ser Val Leu Ser Pro Ser Glu 
                85                  90                  95      


Ala Cys Gly Leu Leu Leu Gly Ser Thr Cys Gly His Trp Asp Ile Phe 
            100                 105                 110         


Ser Ser Trp Asn Ile Ser Leu Pro Thr Val Pro Lys Pro Pro Pro Lys 
        115                 120                 125             


Pro Pro Ser Pro Pro Ala Pro Gly Ala Pro Val Ser Arg Ile Leu Phe 
    130                 135                 140                 


Leu Thr Asp Leu His Trp Asp His Asp Tyr Leu Glu Gly Thr Asp Pro 
145                 150                 155                 160 


Asp Cys Ala Asp Pro Leu Cys Cys Arg Arg Gly Ser Gly Leu Pro Pro 
                165                 170                 175     


Ala Ser Arg Pro Gly Ala Gly Tyr Trp Gly Glu Tyr Ser Lys Cys Asp 
            180                 185                 190         


Leu Pro Leu Arg Thr Leu Glu Ser Leu Leu Ser Gly Leu Gly Pro Ala 
        195                 200                 205             


Gly Pro Phe Asp Met Val Tyr Trp Thr Gly Asp Ile Pro Ala His Asp 
    210                 215                 220                 


Val Trp His Gln Thr Arg Gln Asp Gln Leu Arg Ala Leu Thr Thr Val 
225                 230                 235                 240 


Thr Ala Leu Val Arg Lys Phe Leu Gly Pro Val Pro Val Tyr Pro Ala 
                245                 250                 255     


Val Gly Asn His Glu Ser Ile Pro Val Asn Ser Phe Pro Pro Pro Phe 
            260                 265                 270         


Ile Glu Gly Asn His Ser Ser Arg Trp Leu Tyr Glu Ala Met Ala Lys 
        275                 280                 285             


Ala Trp Glu Pro Trp Leu Pro Ala Glu Ala Leu Arg Thr Leu Arg Ile 
    290                 295                 300                 


Gly Gly Phe Tyr Ala Leu Ser Pro Tyr Pro Gly Leu Arg Leu Ile Ser 
305                 310                 315                 320 


Leu Asn Met Asn Phe Cys Ser Arg Glu Asn Phe Trp Leu Leu Ile Asn 
                325                 330                 335     


Ser Thr Asp Pro Ala Gly Gln Leu Gln Trp Leu Val Gly Glu Leu Gln 
            340                 345                 350         


Ala Ala Glu Asp Arg Gly Asp Lys Val His Ile Ile Gly His Ile Pro 
        355                 360                 365             


Pro Gly His Cys Leu Lys Ser Trp Ser Trp Asn Tyr Tyr Arg Ile Val 
    370                 375                 380                 


Ala Arg Tyr Glu Asn Thr Leu Ala Ala Gln Phe Phe Gly His Thr His 
385                 390                 395                 400 


Val Asp Glu Phe Glu Val Phe Tyr Asp Glu Glu Thr Leu Ser Arg Pro 
                405                 410                 415     


Leu Ala Val Ala Phe Leu Ala Pro Ser Ala Thr Thr Tyr Ile Gly Leu 
            420                 425                 430         


Asn Pro Gly Tyr Arg Val Tyr Gln Ile Asp Gly Asn Tyr Ser Arg Ser 
        435                 440                 445             


Ser His Val Val Leu Asp His Glu Thr Tyr Ile Leu Asn Leu Thr Gln 
    450                 455                 460                 


Ala Asn Ile Pro Gly Ala Ile Pro His Trp Gln Leu Leu Tyr Arg Ala 
465                 470                 475                 480 


Arg Glu Thr Tyr Gly Leu Pro Asn Thr Leu Pro Thr Ala Trp His Asn 
                485                 490                 495     


Leu Val Tyr Arg Met Arg Gly Asp Met Gln Leu Phe Gln Thr Phe Trp 
            500                 505                 510         


Phe Leu Tyr His Lys Gly His Pro Pro Ser Glu Pro Cys Gly Thr Pro 
        515                 520                 525             


Cys Arg Leu Ala Thr Leu Cys Ala Gln Leu Ser Ala Arg Ala Asp Ser 
    530                 535                 540                 


Pro Ala Leu Cys Arg His Leu Met Pro Asp Gly Ser Leu Pro Glu Ala 
545                 550                 555                 560 


Gln Ser Leu Trp Pro Arg Pro Leu Phe Cys 
                565                 570 


<210>  5
<211>  629
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Pro Arg Tyr Gly Ala Ser Leu Arg Gln Ser Cys Pro Arg Ser Gly 
1               5                   10                  15      


Arg Glu Gln Gly Gln Asp Gly Thr Ala Gly Ala Pro Gly Leu Leu Trp 
            20                  25                  30          


Met Gly Leu Val Leu Ala Leu Ala Leu Ala Leu Ala Leu Ala Leu Ser 
        35                  40                  45              


Asp Ser Arg Val Leu Trp Ala Pro Ala Glu Ala His Pro Leu Ser Pro 
    50                  55                  60                  


Gln Gly His Pro Ala Arg Leu His Arg Ile Val Pro Arg Leu Arg Asp 
65                  70                  75                  80  


Val Phe Gly Trp Gly Asn Leu Thr Cys Pro Ile Cys Lys Gly Leu Phe 
                85                  90                  95      


Thr Ala Ile Asn Leu Gly Leu Lys Lys Glu Pro Asn Val Ala Arg Val 
            100                 105                 110         


Gly Ser Val Ala Ile Lys Leu Cys Asn Leu Leu Lys Ile Ala Pro Pro 
        115                 120                 125             


Ala Val Cys Gln Ser Ile Val His Leu Phe Glu Asp Asp Met Val Glu 
    130                 135                 140                 


Val Trp Arg Arg Ser Val Leu Ser Pro Ser Glu Ala Cys Gly Leu Leu 
145                 150                 155                 160 


Leu Gly Ser Thr Cys Gly His Trp Asp Ile Phe Ser Ser Trp Asn Ile 
                165                 170                 175     


Ser Leu Pro Thr Val Pro Lys Pro Pro Pro Lys Pro Pro Ser Pro Pro 
            180                 185                 190         


Ala Pro Gly Ala Pro Val Ser Arg Ile Leu Phe Leu Thr Asp Leu His 
        195                 200                 205             


Trp Asp His Asp Tyr Leu Glu Gly Thr Asp Pro Asp Cys Ala Asp Pro 
    210                 215                 220                 


Leu Cys Cys Arg Arg Gly Ser Gly Leu Pro Pro Ala Ser Arg Pro Gly 
225                 230                 235                 240 


Ala Gly Tyr Trp Gly Glu Tyr Ser Lys Cys Asp Leu Pro Leu Arg Thr 
                245                 250                 255     


Leu Glu Ser Leu Leu Ser Gly Leu Gly Pro Ala Gly Pro Phe Asp Met 
            260                 265                 270         


Val Tyr Trp Thr Gly Asp Ile Pro Ala His Asp Val Trp His Gln Thr 
        275                 280                 285             


Arg Gln Asp Gln Leu Arg Ala Leu Thr Thr Val Thr Ala Leu Val Arg 
    290                 295                 300                 


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


Ser Thr Pro Val Asn Ser Phe Pro Pro Pro Phe Ile Glu Gly Asn His 
                325                 330                 335     


Ser Ser Arg Trp Leu Tyr Glu Ala Met Ala Lys Ala Trp Glu Pro Trp 
            340                 345                 350         


Leu Pro Ala Glu Ala Leu Arg Thr Leu Arg Ile Gly Gly Phe Tyr Ala 
        355                 360                 365             


Leu Ser Pro Tyr Pro Gly Leu Arg Leu Ile Ser Leu Asn Met Asn Phe 
    370                 375                 380                 


Cys Ser Arg Glu Asn Phe Trp Leu Leu Ile Asn Ser Thr Asp Pro Ala 
385                 390                 395                 400 


Gly Gln Leu Gln Trp Leu Val Gly Glu Leu Gln Ala Ala Glu Asp Arg 
                405                 410                 415     


Gly Asp Lys Val His Ile Ile Gly His Ile Pro Pro Gly His Cys Leu 
            420                 425                 430         


Lys Ser Trp Ser Trp Asn Tyr Tyr Arg Ile Val Ala Arg Tyr Glu Asn 
        435                 440                 445             


Thr Leu Ala Ala Gln Phe Phe Gly His Thr His Val Asp Glu Phe Glu 
    450                 455                 460                 


Val Phe Tyr Asp Glu Glu Thr Leu Ser Arg Pro Leu Ala Val Ala Phe 
465                 470                 475                 480 


Leu Ala Pro Ser Ala Thr Thr Tyr Ile Gly Leu Asn Pro Gly Tyr Arg 
                485                 490                 495     


Val Tyr Gln Ile Asp Gly Asn Tyr Ser Gly Ser Ser His Val Val Leu 
            500                 505                 510         


Asp His Glu Thr Tyr Ile Leu Asn Leu Thr Gln Ala Asn Ile Pro Gly 
        515                 520                 525             


Ala Ile Pro His Trp Gln Leu Leu Tyr Arg Ala Arg Glu Thr Tyr Gly 
    530                 535                 540                 


Leu Pro Asn Thr Leu Pro Thr Ala Trp His Asn Leu Val Tyr Arg Met 
545                 550                 555                 560 


Arg Gly Asp Met Gln Leu Phe Gln Thr Phe Trp Phe Leu Tyr His Lys 
                565                 570                 575     


Gly His Pro Pro Ser Glu Pro Cys Gly Thr Pro Cys Arg Leu Ala Thr 
            580                 585                 590         


Leu Cys Ala Gln Leu Ser Ala Arg Ala Asp Ser Pro Ala Leu Cys Arg 
        595                 600                 605             


His Leu Met Pro Asp Gly Ser Leu Pro Glu Ala Gln Ser Leu Trp Pro 
    610                 615                 620                 


Arg Pro Leu Phe Cys 
625                 


<210>  6
<211>  570
<212>  PRT
<213>  Homo sapiens

<400>  6

His Pro Leu Ser Pro Gln Gly His Pro Ala Arg Leu His Arg Ile Val 
1               5                   10                  15      


Pro Arg Leu Arg Asp Val Phe Gly Trp Gly Asn Leu Thr Cys Pro Ile 
            20                  25                  30          


Cys Lys Gly Leu Phe Thr Ala Ile Asn Leu Gly Leu Lys Lys Glu Pro 
        35                  40                  45              


Asn Val Ala Arg Val Gly Ser Val Ala Ile Lys Leu Cys Asn Leu Leu 
    50                  55                  60                  


Lys Ile Ala Pro Pro Ala Val Cys Gln Ser Ile Val His Leu Phe Glu 
65                  70                  75                  80  


Asp Asp Met Val Glu Val Trp Arg Arg Ser Val Leu Ser Pro Ser Glu 
                85                  90                  95      


Ala Cys Gly Leu Leu Leu Gly Ser Thr Cys Gly His Trp Asp Ile Phe 
            100                 105                 110         


Ser Ser Trp Asn Ile Ser Leu Pro Thr Val Pro Lys Pro Pro Pro Lys 
        115                 120                 125             


Pro Pro Ser Pro Pro Ala Pro Gly Ala Pro Val Ser Arg Ile Leu Phe 
    130                 135                 140                 


Leu Thr Asp Leu His Trp Asp His Asp Tyr Leu Glu Gly Thr Asp Pro 
145                 150                 155                 160 


Asp Cys Ala Asp Pro Leu Cys Cys Arg Arg Gly Ser Gly Leu Pro Pro 
                165                 170                 175     


Ala Ser Arg Pro Gly Ala Gly Tyr Trp Gly Glu Tyr Ser Lys Cys Asp 
            180                 185                 190         


Leu Pro Leu Arg Thr Leu Glu Ser Leu Leu Ser Gly Leu Gly Pro Ala 
        195                 200                 205             


Gly Pro Phe Asp Met Val Tyr Trp Thr Gly Asp Ile Pro Ala His Asp 
    210                 215                 220                 


Val Trp His Gln Thr Arg Gln Asp Gln Leu Arg Ala Leu Thr Thr Val 
225                 230                 235                 240 


Thr Ala Leu Val Arg Lys Phe Leu Gly Pro Val Pro Val Tyr Pro Ala 
                245                 250                 255     


Val Gly Asn His Glu Ser Thr Pro Val Asn Ser Phe Pro Pro Pro Phe 
            260                 265                 270         


Ile Glu Gly Asn His Ser Ser Arg Trp Leu Tyr Glu Ala Met Ala Lys 
        275                 280                 285             


Ala Trp Glu Pro Trp Leu Pro Ala Glu Ala Leu Arg Thr Leu Arg Ile 
    290                 295                 300                 


Gly Gly Phe Tyr Ala Leu Ser Pro Tyr Pro Gly Leu Arg Leu Ile Ser 
305                 310                 315                 320 


Leu Asn Met Asn Phe Cys Ser Arg Glu Asn Phe Trp Leu Leu Ile Asn 
                325                 330                 335     


Ser Thr Asp Pro Ala Gly Gln Leu Gln Trp Leu Val Gly Glu Leu Gln 
            340                 345                 350         


Ala Ala Glu Asp Arg Gly Asp Lys Val His Ile Ile Gly His Ile Pro 
        355                 360                 365             


Pro Gly His Cys Leu Lys Ser Trp Ser Trp Asn Tyr Tyr Arg Ile Val 
    370                 375                 380                 


Ala Arg Tyr Glu Asn Thr Leu Ala Ala Gln Phe Phe Gly His Thr His 
385                 390                 395                 400 


Val Asp Glu Phe Glu Val Phe Tyr Asp Glu Glu Thr Leu Ser Arg Pro 
                405                 410                 415     


Leu Ala Val Ala Phe Leu Ala Pro Ser Ala Thr Thr Tyr Ile Gly Leu 
            420                 425                 430         


Asn Pro Gly Tyr Arg Val Tyr Gln Ile Asp Gly Asn Tyr Ser Gly Ser 
        435                 440                 445             


Ser His Val Val Leu Asp His Glu Thr Tyr Ile Leu Asn Leu Thr Gln 
    450                 455                 460                 


Ala Asn Ile Pro Gly Ala Ile Pro His Trp Gln Leu Leu Tyr Arg Ala 
465                 470                 475                 480 


Arg Glu Thr Tyr Gly Leu Pro Asn Thr Leu Pro Thr Ala Trp His Asn 
                485                 490                 495     


Leu Val Tyr Arg Met Arg Gly Asp Met Gln Leu Phe Gln Thr Phe Trp 
            500                 505                 510         


Phe Leu Tyr His Lys Gly His Pro Pro Ser Glu Pro Cys Gly Thr Pro 
        515                 520                 525             


Cys Arg Leu Ala Thr Leu Cys Ala Gln Leu Ser Ala Arg Ala Asp Ser 
    530                 535                 540                 


Pro Ala Leu Cys Arg His Leu Met Pro Asp Gly Ser Leu Pro Glu Ala 
545                 550                 555                 560 


Gln Ser Leu Trp Pro Arg Pro Leu Phe Cys 
                565                 570 


