                               SEQUENCE LISTING

<110> ALNYLAM PHARMACEUTICALS, INC.
 
<120> NEUROFILAMENT LIGHT CHAIN (NFL) AS A BIOMARKER FOR TRANSTHYRETIN 
      AMYLOIDOSIS POLYNEUROPATHY

<130> A2038-7233WO

<140>
<141>

<150> 63/044,163
<151> 2020-06-25

<150> 62/925,623
<151> 2019-10-24

<150> 62/894,237
<151> 2019-08-30

<160> 26    

<170> PatentIn version 3.5

<210> 1
<211> 543
<212> PRT
<213> Homo sapiens

<400> 1
Met Ser Ser Phe Ser Tyr Glu Pro Tyr Tyr Ser Thr Ser Tyr Lys Arg 
1               5                   10                  15      


Arg Tyr Val Glu Thr Pro Arg Val His Ile Ser Ser Val Arg Ser Gly 
            20                  25                  30          


Tyr Ser Thr Ala Arg Ser Ala Tyr Ser Ser Tyr Ser Ala Pro Val Ser 
        35                  40                  45              


Ser Ser Leu Ser Val Arg Arg Ser Tyr Ser Ser Ser Ser Gly Ser Leu 
    50                  55                  60                  


Met Pro Ser Leu Glu Asn Leu Asp Leu Ser Gln Val Ala Ala Ile Ser 
65                  70                  75                  80  


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


Leu Asn Asp Arg Phe Ala Ser Phe Ile Glu Arg Val His Glu Leu Glu 
            100                 105                 110         


Gln Gln Asn Lys Val Leu Glu Ala Glu Leu Leu Val Leu Arg Gln Lys 
        115                 120                 125             


His Ser Glu Pro Ser Arg Phe Arg Ala Leu Tyr Glu Gln Glu Ile Arg 
    130                 135                 140                 


Asp Leu Arg Leu Ala Ala Glu Asp Ala Thr Asn Glu Lys Gln Ala Leu 
145                 150                 155                 160 


Gln Gly Glu Arg Glu Gly Leu Glu Glu Thr Leu Arg Asn Leu Gln Ala 
                165                 170                 175     


Arg Tyr Glu Glu Glu Val Leu Ser Arg Glu Asp Ala Glu Gly Arg Leu 
            180                 185                 190         


Met Glu Ala Arg Lys Gly Ala Asp Glu Ala Ala Leu Ala Arg Ala Glu 
        195                 200                 205             


Leu Glu Lys Arg Ile Asp Ser Leu Met Asp Glu Ile Ser Phe Leu Lys 
    210                 215                 220                 


Lys Val His Glu Glu Glu Ile Ala Glu Leu Gln Ala Gln Ile Gln Tyr 
225                 230                 235                 240 


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


Ala Leu Lys Asp Ile Arg Ala Gln Tyr Glu Lys Leu Ala Ala Lys Asn 
            260                 265                 270         


Met Gln Asn Ala Glu Glu Trp Phe Lys Ser Arg Phe Thr Val Leu Thr 
        275                 280                 285             


Glu Ser Ala Ala Lys Asn Thr Asp Ala Val Arg Ala Ala Lys Asp Glu 
    290                 295                 300                 


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


Ala Cys Arg Gly Met Asn Glu Ala Leu Glu Lys Gln Leu Gln Glu Leu 
                325                 330                 335     


Glu Asp Lys Gln Asn Ala Asp Ile Ser Ala Met Gln Asp Thr Ile Asn 
            340                 345                 350         


Lys Leu Glu Asn Glu Leu Arg Thr Thr Lys Ser Glu Met Ala Arg Tyr 
        355                 360                 365             


Leu Lys Glu Tyr Gln Asp Leu Leu Asn Val Lys Met Ala Leu Asp Ile 
    370                 375                 380                 


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


Ser Phe Thr Ser Val Gly Ser Ile Thr Ser Gly Tyr Ser Gln Ser Ser 
                405                 410                 415     


Gln Val Phe Gly Arg Ser Ala Tyr Gly Gly Leu Gln Thr Ser Ser Tyr 
            420                 425                 430         


Leu Met Ser Thr Arg Ser Phe Pro Ser Tyr Tyr Thr Ser His Val Gln 
        435                 440                 445             


Glu Glu Gln Ile Glu Val Glu Glu Thr Ile Glu Ala Ala Lys Ala Glu 
    450                 455                 460                 


Glu Ala Lys Asp Glu Pro Pro Ser Glu Gly Glu Ala Glu Glu Glu Glu 
465                 470                 475                 480 


Lys Asp Lys Glu Glu Ala Glu Glu Glu Glu Ala Ala Glu Glu Glu Glu 
                485                 490                 495     


Ala Ala Lys Glu Glu Ser Glu Glu Ala Lys Glu Glu Glu Glu Gly Gly 
            500                 505                 510         


Glu Gly Glu Glu Gly Glu Glu Thr Lys Glu Ala Glu Glu Glu Glu Lys 
        515                 520                 525             


Lys Val Glu Gly Ala Gly Glu Glu Gln Ala Ala Lys Lys Lys Asp 
    530                 535                 540             


<210> 2
<211> 21
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 2
ugggauuuca uguaaccaag a                                                 21


<210> 3
<211> 21
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide"

<400> 3
auggaauacu cuugguuact t                                                 21


<210> 4
<211> 23
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 4
ucuugguuac augaaauccc auc                                               23


<210> 5
<211> 20
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 5
tcttggttac atgaaatccc                                                   20


<210> 6
<211> 20
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 6
tcttggttac atgaaatccc                                                   20


<210> 7
<211> 19
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 7
auggaauacu cuugguuac                                                    19


<210> 8
<211> 19
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<400> 8
guaaccaaga guauuccau                                                    19


<210> 9
<211> 21
<212> DNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"

<220>
<221> source
<223> /note="Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide"

<400> 9
guaaccaaga guauuccaut t                                                 21


<210> 10
<211> 284
<212> PRT
<213> Homo sapiens

<400> 10
Met Ser Ser Phe Ser Tyr Glu Pro Tyr Tyr Ser Thr Ser Tyr Lys Arg 
1               5                   10                  15      


Arg Tyr Val Glu Thr Pro Arg Val His Ile Ser Ser Val Arg Ser Gly 
            20                  25                  30          


Tyr Ser Thr Ala Arg Ser Ala Tyr Ser Ser Tyr Ser Ala Pro Val Ser 
        35                  40                  45              


Ser Ser Leu Ser Val Arg Arg Ser Tyr Ser Ser Ser Ser Gly Ser Leu 
    50                  55                  60                  


Met Pro Ser Leu Glu Asn Leu Asp Leu Ser Gln Val Ala Ala Ile Ser 
65                  70                  75                  80  


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


Leu Asn Asp Arg Phe Ala Ser Phe Ile Glu Arg Val His Glu Leu Glu 
            100                 105                 110         


Gln Gln Asn Lys Val Leu Glu Ala Glu Leu Leu Val Leu Arg Gln Lys 
        115                 120                 125             


His Ser Glu Pro Ser Arg Phe Arg Ala Leu Tyr Glu Gln Glu Ile Arg 
    130                 135                 140                 


Asp Leu Arg Leu Ala Ala Glu Asp Ala Thr Asn Glu Lys Gln Ala Leu 
145                 150                 155                 160 


Gln Gly Glu Arg Glu Gly Leu Glu Glu Thr Leu Arg Asn Leu Gln Ala 
                165                 170                 175     


Arg Tyr Glu Glu Glu Val Leu Ser Arg Glu Asp Ala Glu Gly Arg Leu 
            180                 185                 190         


Met Glu Ala Arg Lys Gly Ala Lys Asn Thr Asp Ala Val Arg Ala Ala 
        195                 200                 205             


Lys Asp Glu Val Ser Glu Ser Arg Arg Leu Leu Lys Ala Lys Thr Leu 
    210                 215                 220                 


Glu Ile Glu Ala Cys Arg Gly Met Asn Glu Ala Leu Glu Lys Gln Leu 
225                 230                 235                 240 


Gln Glu Leu Glu Asp Lys Gln Asn Ala Asp Ile Ser Val Met Gln Asp 
                245                 250                 255     


Thr Ile Asn Lys Leu Glu Asn Glu Leu Arg Thr Thr Lys Ser Glu Met 
            260                 265                 270         


Ala Arg Tyr Leu Lys Glu Tyr Gln Asp Leu Leu Thr 
        275                 280                 


<210> 11
<211> 272
<212> PRT
<213> Homo sapiens

<400> 11
Met His Leu Arg Leu Ile Ser Trp Leu Phe Ile Ile Leu Asn Phe Met 
1               5                   10                  15      


Glu Tyr Ile Gly Ser Gln Asn Ala Ser Arg Gly Arg Arg Gln Arg Arg 
            20                  25                  30          


Met His Pro Asn Val Ser Gln Gly Cys Gln Gly Gly Cys Ala Thr Cys 
        35                  40                  45              


Ser Asp Tyr Asn Gly Cys Leu Ser Cys Lys Pro Arg Leu Phe Phe Ala 
    50                  55                  60                  


Leu Glu Arg Ile Gly Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys 
65                  70                  75                  80  


Pro Ser Gly Tyr Tyr Gly Thr Arg Tyr Pro Asp Ile Asn Lys Cys Thr 
                85                  90                  95      


Lys Cys Lys Ala Asp Cys Asp Thr Cys Phe Asn Lys Asn Phe Cys Thr 
            100                 105                 110         


Lys Cys Lys Ser Gly Phe Tyr Leu His Leu Gly Lys Cys Leu Asp Asn 
        115                 120                 125             


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


Ile Val His Cys Glu Val Ser Glu Trp Asn Pro Trp Ser Pro Cys Thr 
145                 150                 155                 160 


Lys Lys Gly Lys Thr Cys Gly Phe Lys Arg Gly Thr Glu Thr Arg Val 
                165                 170                 175     


Arg Glu Ile Ile Gln His Pro Ser Ala Lys Gly Asn Leu Cys Pro Pro 
            180                 185                 190         


Thr Asn Glu Thr Arg Lys Cys Thr Val Gln Arg Lys Lys Cys Gln Lys 
        195                 200                 205             


Gly Glu Arg Gly Lys Lys Gly Arg Glu Arg Lys Arg Lys Lys Pro Asn 
    210                 215                 220                 


Lys Gly Glu Ser Lys Glu Ala Ile Pro Asp Ser Lys Ser Leu Glu Ser 
225                 230                 235                 240 


Ser Lys Glu Ile Pro Glu Gln Arg Glu Asn Lys Gln Gln Gln Lys Lys 
                245                 250                 255     


Arg Lys Val Gln Asp Lys Gln Lys Ser Val Ser Val Ser Thr Val His 
            260                 265                 270         


<210> 12
<211> 203
<212> PRT
<213> Homo sapiens

<400> 12
Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys Pro Ser Gly Tyr Tyr 
1               5                   10                  15      


Gly Thr Arg Tyr Pro Asp Ile Asn Lys Cys Thr Lys Cys Lys Ala Asp 
            20                  25                  30          


Cys Asp Thr Cys Phe Asn Lys Asn Phe Cys Thr Lys Cys Lys Ser Gly 
        35                  40                  45              


Phe Tyr Leu His Leu Gly Lys Cys Leu Asp Asn Cys Pro Glu Gly Leu 
    50                  55                  60                  


Glu Ala Asn Asn His Thr Met Glu Cys Val Ser Ile Val His Cys Glu 
65                  70                  75                  80  


Val Ser Glu Trp Asn Pro Trp Ser Pro Cys Thr Lys Lys Gly Lys Thr 
                85                  90                  95      


Cys Gly Phe Lys Arg Gly Thr Glu Thr Arg Val Arg Glu Ile Ile Gln 
            100                 105                 110         


His Pro Ser Ala Lys Gly Asn Leu Cys Pro Pro Thr Asn Glu Thr Arg 
        115                 120                 125             


Lys Cys Thr Val Gln Arg Lys Lys Cys Gln Lys Gly Glu Arg Gly Lys 
    130                 135                 140                 


Lys Gly Arg Glu Arg Lys Arg Lys Lys Pro Asn Lys Gly Glu Ser Lys 
145                 150                 155                 160 


Glu Ala Ile Pro Asp Ser Lys Ser Leu Glu Ser Ser Lys Glu Ile Pro 
                165                 170                 175     


Glu Gln Arg Glu Asn Lys Gln Gln Gln Lys Lys Arg Lys Val Gln Asp 
            180                 185                 190         


Lys Gln Lys Ser Val Ser Val Ser Thr Val His 
        195                 200             


<210> 13
<211> 224
<212> PRT
<213> Homo sapiens

<400> 13
Met His Leu Arg Leu Ile Ser Trp Leu Phe Ile Ile Leu Asn Phe Met 
1               5                   10                  15      


Glu Tyr Ile Gly Ser Gln Asn Ala Ser Arg Gly Arg Arg Gln Arg Arg 
            20                  25                  30          


Met His Pro Asn Val Ser Gln Gly Cys Gln Gly Gly Cys Ala Thr Cys 
        35                  40                  45              


Ser Asp Tyr Asn Gly Cys Leu Ser Cys Lys Pro Arg Leu Phe Phe Ala 
    50                  55                  60                  


Leu Glu Arg Ile Gly Met Lys Gln Ile Gly Val Cys Leu Ser Ser Cys 
65                  70                  75                  80  


Pro Ser Gly Tyr Tyr Gly Thr Arg Tyr Pro Asp Ile Asn Lys Cys Thr 
                85                  90                  95      


Lys Cys Lys Ala Asp Cys Asp Thr Cys Phe Asn Lys Asn Phe Cys Thr 
            100                 105                 110         


Lys Cys Lys Ser Gly Phe Tyr Leu His Leu Gly Lys Cys Leu Asp Asn 
        115                 120                 125             


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


Ile Val His Cys Glu Val Ser Glu Trp Asn Pro Trp Ser Pro Cys Thr 
145                 150                 155                 160 


Lys Lys Gly Lys Thr Cys Gly Phe Lys Arg Gly Thr Glu Thr Arg Val 
                165                 170                 175     


Arg Glu Ile Ile Gln His Pro Ser Ala Lys Gly Asn Leu Cys Pro Pro 
            180                 185                 190         


Thr Asn Glu Thr Arg Lys Cys Thr Val Gln Arg Lys Lys Cys Gln Lys 
        195                 200                 205             


Gly Glu Arg Gly Arg Thr Ser Arg Gly Asp Glu Arg Cys Phe Asn His 
    210                 215                 220                 


<210> 14
<211> 553
<212> PRT
<213> Homo sapiens

<400> 14
Met Thr Trp Arg Met Gly Pro Arg Phe Thr Met Leu Leu Ala Met Trp 
1               5                   10                  15      


Leu Val Cys Gly Ser Glu Pro His Pro His Ala Thr Ile Arg Gly Ser 
            20                  25                  30          


His Gly Gly Arg Lys Val Pro Leu Val Ser Pro Asp Ser Ser Arg Pro 
        35                  40                  45              


Ala Arg Phe Leu Arg His Thr Gly Arg Ser Arg Gly Ile Glu Arg Ser 
    50                  55                  60                  


Thr Leu Glu Glu Pro Asn Leu Gln Pro Leu Gln Arg Arg Arg Ser Val 
65                  70                  75                  80  


Pro Val Leu Arg Leu Ala Arg Pro Thr Glu Pro Pro Ala Arg Ser Asp 
                85                  90                  95      


Ile Asn Gly Ala Ala Val Arg Pro Glu Gln Arg Pro Ala Ala Arg Gly 
            100                 105                 110         


Ser Pro Arg Glu Met Ile Arg Asp Glu Gly Ser Ser Ala Arg Ser Arg 
        115                 120                 125             


Met Leu Arg Phe Pro Ser Gly Ser Ser Ser Pro Asn Ile Leu Ala Ser 
    130                 135                 140                 


Phe Ala Gly Lys Asn Arg Val Trp Val Ile Ser Ala Pro His Ala Ser 
145                 150                 155                 160 


Glu Gly Tyr Tyr Arg Leu Met Met Ser Leu Leu Lys Asp Asp Val Tyr 
                165                 170                 175     


Cys Glu Leu Ala Glu Arg His Ile Gln Gln Ile Val Leu Phe His Gln 
            180                 185                 190         


Ala Gly Glu Glu Gly Gly Lys Val Arg Arg Ile Thr Ser Glu Gly Gln 
        195                 200                 205             


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


Phe Leu Lys Leu Glu Lys Gly Lys Phe Gly Met Val Leu Leu Lys Lys 
225                 230                 235                 240 


Thr Leu Gln Val Glu Glu Arg Tyr Pro Tyr Pro Val Arg Leu Glu Ala 
                245                 250                 255     


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


Arg Gln Lys Gly Phe Val Gln Lys Cys Lys Ala Ser Gly Val Glu Gly 
        275                 280                 285             


Gln Val Val Ala Glu Gly Asn Asp Gly Gly Gly Gly Ala Gly Arg Pro 
    290                 295                 300                 


Ser Leu Gly Ser Glu Lys Lys Lys Glu Asp Pro Arg Arg Ala Gln Val 
305                 310                 315                 320 


Pro Pro Thr Arg Glu Ser Arg Val Lys Val Leu Arg Lys Leu Ala Ala 
                325                 330                 335     


Thr Ala Pro Ala Leu Pro Gln Pro Pro Ser Thr Pro Arg Ala Thr Thr 
            340                 345                 350         


Leu Pro Pro Ala Pro Ala Thr Thr Val Thr Arg Ser Thr Ser Arg Ala 
        355                 360                 365             


Val Thr Val Ala Ala Arg Pro Met Thr Thr Thr Ala Phe Pro Thr Thr 
    370                 375                 380                 


Gln Arg Pro Trp Thr Pro Ser Pro Ser His Arg Pro Pro Thr Thr Thr 
385                 390                 395                 400 


Glu Val Ile Thr Ala Arg Arg Pro Ser Val Ser Glu Asn Leu Tyr Pro 
                405                 410                 415     


Pro Ser Arg Lys Asp Gln His Arg Glu Arg Pro Gln Thr Thr Arg Arg 
            420                 425                 430         


Pro Ser Lys Ala Thr Ser Leu Glu Ser Phe Thr Asn Ala Pro Pro Thr 
        435                 440                 445             


Thr Ile Ser Glu Pro Ser Thr Arg Ala Ala Gly Pro Gly Arg Phe Arg 
    450                 455                 460                 


Asp Asn Arg Met Asp Arg Arg Glu His Gly His Arg Asp Pro Asn Val 
465                 470                 475                 480 


Val Pro Gly Pro Pro Lys Pro Ala Lys Glu Lys Pro Pro Lys Lys Lys 
                485                 490                 495     


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


Ser Arg Pro Thr Ala Ser Gln Leu Glu Asp Glu Leu Gln Val Gly Asn 
        515                 520                 525             


Val Pro Leu Lys Lys Ala Lys Glu Ser Lys Lys His Glu Lys Leu Glu 
    530                 535                 540                 


Lys Pro Glu Lys Lys Lys Glu Lys Lys 
545                 550             


<210> 15
<211> 331
<212> PRT
<213> Homo sapiens

<400> 15
Glu Gly Lys Arg Arg Leu Leu Leu Ile Thr Ala Pro Lys Ala Glu Asn 
1               5                   10                  15      


Asn Met Tyr Val Gln Gln Arg Asp Glu Tyr Leu Glu Ser Phe Cys Lys 
            20                  25                  30          


Met Ala Thr Arg Lys Ile Ser Val Ile Thr Ile Phe Gly Pro Val Asn 
        35                  40                  45              


Asn Ser Thr Met Lys Ile Asp His Phe Gln Leu Asp Asn Glu Lys Pro 
    50                  55                  60                  


Met Arg Val Val Asp Asp Glu Asp Leu Val Asp Gln Arg Leu Ile Ser 
65                  70                  75                  80  


Glu Leu Arg Lys Glu Tyr Gly Met Thr Tyr Asn Asp Phe Phe Met Val 
                85                  90                  95      


Leu Thr Asp Val Asp Leu Arg Val Lys Gln Tyr Tyr Glu Val Pro Ile 
            100                 105                 110         


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


Lys Asp Met Glu Lys Gln Lys Lys Glu Gly Ile Val Cys Lys Glu Asp 
    130                 135                 140                 


Lys Lys Gln Ser Leu Glu Asn Phe Leu Ser Arg Phe Arg Trp Arg Arg 
145                 150                 155                 160 


Arg Leu Leu Val Ile Ser Ala Pro Asn Asp Glu Asp Trp Ala Tyr Ser 
                165                 170                 175     


Gln Gln Leu Ser Ala Leu Ser Gly Gln Ala Cys Asn Phe Gly Leu Arg 
            180                 185                 190         


His Ile Thr Ile Leu Lys Leu Leu Gly Val Gly Glu Glu Val Gly Gly 
        195                 200                 205             


Val Leu Glu Leu Phe Pro Ile Asn Gly Gly Ser Val Val Glu Arg Glu 
    210                 215                 220                 


Asp Val Pro Ala His Leu Val Lys Asp Ile Arg Asn Tyr Phe Gln Val 
225                 230                 235                 240 


Ser Pro Glu Tyr Phe Ser Met Leu Leu Val Gly Lys Asp Gly Asn Val 
                245                 250                 255     


Lys Ser Trp Tyr Pro Ser Pro Met Trp Ser Met Val Ile Val Tyr Asp 
            260                 265                 270         


Leu Ile Asp Ser Met Gln Leu Arg Arg Gln Glu Met Ala Ile Gln Gln 
        275                 280                 285             


Ser Leu Gly Met Arg Cys Pro Glu Asp Glu Tyr Ala Gly Tyr Gly Tyr 
    290                 295                 300                 


His Ser Tyr His Gln Gly Tyr Gln Asp Gly Tyr Gln Asp Asp Tyr Arg 
305                 310                 315                 320 


His His Glu Ser Tyr His His Gly Tyr Pro Tyr 
                325                 330     


<210> 16
<211> 85
<212> PRT
<213> Homo sapiens

<400> 16
Met Leu Leu Val Gly Lys Asp Gly Asn Val Lys Ser Trp Tyr Pro Ser 
1               5                   10                  15      


Pro Met Trp Ser Met Val Ile Val Tyr Asp Leu Ile Asp Ser Met Gln 
            20                  25                  30          


Leu Arg Arg Gln Glu Met Ala Ile Gln Gln Ser Leu Gly Met Arg Cys 
        35                  40                  45              


Pro Glu Asp Glu Tyr Ala Gly Tyr Gly Tyr His Ser Tyr His Gln Gly 
    50                  55                  60                  


Tyr Gln Asp Gly Tyr Gln Asp Asp Tyr Arg His His Glu Ser Tyr His 
65                  70                  75                  80  


His Gly Tyr Pro Tyr 
                85  


<210> 17
<211> 297
<212> PRT
<213> Homo sapiens

<400> 17
Met Asp Cys Gln Glu Asn Glu Tyr Trp Asp Gln Trp Gly Arg Cys Val 
1               5                   10                  15      


Thr Cys Gln Arg Cys Gly Pro Gly Gln Glu Leu Ser Lys Asp Cys Gly 
            20                  25                  30          


Tyr Gly Glu Gly Gly Asp Ala Tyr Cys Thr Ala Cys Pro Pro Arg Arg 
        35                  40                  45              


Tyr Lys Ser Ser Trp Gly His His Arg Cys Gln Ser Cys Ile Thr Cys 
    50                  55                  60                  


Ala Val Ile Asn Arg Val Gln Lys Val Asn Cys Thr Ala Thr Ser Asn 
65                  70                  75                  80  


Ala Val Cys Gly Asp Cys Leu Pro Arg Phe Tyr Arg Lys Thr Arg Ile 
                85                  90                  95      


Gly Gly Leu Gln Asp Gln Glu Cys Ile Pro Cys Thr Lys Gln Thr Pro 
            100                 105                 110         


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


Ala Pro Thr Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser 
    130                 135                 140                 


Ser Leu Leu Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu 
145                 150                 155                 160 


Tyr Cys Lys Gln Phe Phe Asn Arg His Cys Gln Arg Gly Gly Leu Leu 
                165                 170                 175     


Gln Phe Glu Ala Asp Lys Thr Ala Lys Glu Glu Ser Leu Phe Pro Val 
            180                 185                 190         


Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val Ser Glu Asn Ile 
        195                 200                 205             


Phe Gln Thr Gln Pro Leu Asn Pro Ile Leu Glu Asp Asp Cys Ser Ser 
    210                 215                 220                 


Thr Ser Gly Phe Pro Thr Gln Glu Ser Phe Thr Met Ala Ser Cys Thr 
225                 230                 235                 240 


Ser Glu Ser His Ser His Trp Val His Ser Pro Ile Glu Cys Thr Glu 
                245                 250                 255     


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


Thr Leu Gly Gly Asn Thr Val Glu Ser Thr Gly Asp Arg Leu Glu Leu 
        275                 280                 285             


Asn Val Pro Phe Glu Val Pro Ser Pro 
    290                 295         


<210> 18
<211> 318
<212> PRT
<213> Homo sapiens

<400> 18
Met Asp Cys Gln Glu Asn Glu Tyr Trp Asp Gln Trp Gly Arg Cys Val 
1               5                   10                  15      


Thr Cys Gln Arg Cys Gly Pro Gly Gln Glu Leu Ser Lys Asp Cys Gly 
            20                  25                  30          


Tyr Gly Glu Gly Gly Asp Ala Tyr Cys Thr Ala Cys Pro Pro Arg Arg 
        35                  40                  45              


Tyr Lys Ser Ser Trp Gly His His Arg Cys Gln Ser Cys Ile Thr Cys 
    50                  55                  60                  


Ala Val Ile Asn Arg Val Gln Lys Val Asn Cys Thr Ala Thr Ser Asn 
65                  70                  75                  80  


Ala Val Cys Gly Asp Cys Leu Pro Arg Phe Tyr Arg Lys Thr Arg Ile 
                85                  90                  95      


Gly Gly Leu Gln Asp Gln Glu Cys Ile Pro Cys Thr Lys Gln Thr Pro 
            100                 105                 110         


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


Ala Pro Thr Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser 
    130                 135                 140                 


Ser Leu Leu Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu 
145                 150                 155                 160 


Tyr Cys Lys Gln Phe Phe Asn Arg His Cys Gln Arg Glu Lys Leu Ile 
                165                 170                 175     


Ile Phe Ser Asp Pro Val Pro Ala Ser Leu Asn Leu Ile Pro Glu Phe 
            180                 185                 190         


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


Ser Leu Phe Pro Val Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln 
    210                 215                 220                 


Val Ser Glu Asn Ile Phe Gln Thr Gln Pro Leu Asn Pro Ile Leu Glu 
225                 230                 235                 240 


Asp Asp Cys Ser Ser Thr Ser Gly Phe Pro Thr Gln Glu Ser Phe Thr 
                245                 250                 255     


Met Ala Ser Cys Thr Ser Glu Ser His Ser His Trp Val His Ser Pro 
            260                 265                 270         


Ile Glu Cys Thr Glu Leu Asp Leu Gln Lys Phe Ser Ser Ser Ala Ser 
        275                 280                 285             


Tyr Thr Gly Ala Glu Thr Leu Gly Gly Asn Thr Val Glu Ser Thr Gly 
    290                 295                 300                 


Asp Arg Leu Glu Leu Asn Val Pro Phe Glu Val Pro Ser Pro 
305                 310                 315             


<210> 19
<211> 173
<212> PRT
<213> Homo sapiens

<400> 19
Met Ser Thr Gly Thr Asn Gly Asp Gly Val Ser Pro Ala Asn Gly Val 
1               5                   10                  15      


Val Leu Asp Arg Ser Tyr Pro Arg Cys Leu Pro Val Glu Leu Ser Gly 
            20                  25                  30          


Gly Arg Tyr Thr His Ser Ala Pro Ser Gly Gly His Thr Cys Cys Thr 
        35                  40                  45              


Gly Gly Leu Leu Gln Phe Glu Ala Asp Lys Thr Ala Lys Glu Glu Ser 
    50                  55                  60                  


Leu Phe Pro Val Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val 
65                  70                  75                  80  


Ser Glu Asn Ile Phe Gln Thr Gln Pro Leu Asn Pro Ile Leu Glu Asp 
                85                  90                  95      


Asp Cys Ser Ser Thr Ser Gly Phe Pro Thr Gln Glu Ser Phe Thr Met 
            100                 105                 110         


Ala Ser Cys Thr Ser Glu Ser His Ser His Trp Val His Ser Pro Ile 
        115                 120                 125             


Glu Cys Thr Glu Leu Asp Leu Gln Lys Phe Ser Ser Ser Ala Ser Tyr 
    130                 135                 140                 


Thr Gly Ala Glu Thr Leu Gly Gly Asn Thr Val Glu Ser Thr Gly Asp 
145                 150                 155                 160 


Arg Leu Glu Leu Asn Val Pro Phe Glu Val Pro Ser Pro 
                165                 170             


<210> 20
<211> 265
<212> PRT
<213> Homo sapiens

<400> 20
Met Ser Thr Gly Thr Asn Gly Asp Gly Val Ser Pro Ala Asn Gly Val 
1               5                   10                  15      


Val Leu Asp Arg Ser Tyr Pro Arg Ile Val Val Met Glu Arg Val Glu 
            20                  25                  30          


Met Pro Thr Ala Gln Pro Ala Leu Leu Ala Gly Thr Lys Ala Ala Gly 
        35                  40                  45              


Ala Thr Thr Asp Val Arg Val Ala Ser Pro Val Leu Ser Ser Ile Val 
    50                  55                  60                  


Phe Arg Arg Ser Thr Ala Gln Leu Pro Leu Met Leu Ser Val Gly Thr 
65                  70                  75                  80  


Val Cys Pro Gly Ala Phe Gln Leu Ser Leu Val Glu Ala Asp Thr Pro 
                85                  90                  95      


Thr Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser Ser Leu 
            100                 105                 110         


Leu Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu Tyr Cys 
        115                 120                 125             


Lys Gln Phe Phe Asn Arg His Cys Gln Arg Val Ala Gly Gly Leu Leu 
    130                 135                 140                 


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


Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val Ser Glu Asn Ile 
                165                 170                 175     


Phe Gln Thr Gln Pro Leu Asn Pro Ile Leu Glu Asp Asp Cys Ser Ser 
            180                 185                 190         


Thr Ser Gly Phe Pro Thr Gln Glu Ser Phe Thr Met Ala Ser Cys Thr 
        195                 200                 205             


Ser Glu Ser His Ser His Trp Val His Ser Pro Ile Glu Cys Thr Glu 
    210                 215                 220                 


Leu Asp Leu Gln Lys Phe Ser Ser Ser Ala Ser Tyr Thr Gly Ala Glu 
225                 230                 235                 240 


Thr Leu Gly Gly Asn Thr Val Glu Ser Thr Gly Asp Arg Leu Glu Leu 
                245                 250                 255     


Asn Val Pro Phe Glu Val Pro Ser Pro 
            260                 265 


<210> 21
<211> 107
<212> PRT
<213> Homo sapiens

<400> 21
Met Ser Thr Gly Thr Asn Gly Asp Gly Val Ser Pro Ala Asn Gly Val 
1               5                   10                  15      


Val Leu Asp Arg Ser Tyr Pro Arg Cys Leu Pro Val Glu Leu Ser Gly 
            20                  25                  30          


Gly Arg Tyr Thr His Ser Ala Pro Ser Gly Gly His Thr Cys Cys Thr 
        35                  40                  45              


Gly Gly Leu Leu Gln Phe Glu Ala Asp Lys Thr Ala Lys Glu Glu Ser 
    50                  55                  60                  


Leu Phe Pro Val Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val 
65                  70                  75                  80  


Ser Trp Ala Pro Gly Ser Leu Ala Gln Leu Phe Ser Leu Asp Ser Val 
                85                  90                  95      


Pro Ile Pro Gln Gln Gln Gln Gly Pro Glu Met 
            100                 105         


<210> 22
<211> 134
<212> PRT
<213> Homo sapiens

<400> 22
Met Gly Thr Val Cys His Leu Pro Thr Val Trp Ser Trp Thr Gly Ala 
1               5                   10                  15      


Ile Gln Gly Ala Phe Gln Leu Ser Leu Val Glu Ala Asp Thr Pro Thr 
            20                  25                  30          


Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser Ser Leu Leu 
        35                  40                  45              


Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu Tyr Cys Lys 
    50                  55                  60                  


Gln Phe Phe Asn Arg His Cys Gln Arg Val Ala Gly Gly Leu Leu Gln 
65                  70                  75                  80  


Phe Glu Ala Asp Lys Thr Ala Lys Glu Glu Ser Leu Phe Pro Val Pro 
                85                  90                  95      


Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val Ser Trp Ala Pro Gly 
            100                 105                 110         


Ser Leu Ala Gln Leu Phe Ser Leu Asp Ser Val Pro Ile Pro Gln Gln 
        115                 120                 125             


Gln Gln Gly Pro Glu Met 
    130                 


<210> 23
<211> 132
<212> PRT
<213> Homo sapiens

<400> 23
Met Gly Thr Val Cys His Leu Pro Thr Val Trp Ser Trp Thr Gly Ala 
1               5                   10                  15      


Ile Gln Gly Ala Phe Gln Leu Ser Leu Val Glu Ala Asp Thr Pro Thr 
            20                  25                  30          


Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser Ser Leu Leu 
        35                  40                  45              


Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu Tyr Cys Lys 
    50                  55                  60                  


Gln Phe Phe Asn Arg His Cys Gln Arg Gly Gly Leu Leu Gln Phe Glu 
65                  70                  75                  80  


Ala Asp Lys Thr Ala Lys Glu Glu Ser Leu Phe Pro Val Pro Pro Ser 
                85                  90                  95      


Lys Glu Thr Ser Ala Glu Ser Gln Val Ser Trp Ala Pro Gly Ser Leu 
            100                 105                 110         


Ala Gln Leu Phe Ser Leu Asp Ser Val Pro Ile Pro Gln Gln Gln Gln 
        115                 120                 125             


Gly Pro Glu Met 
    130         


<210> 24
<211> 299
<212> PRT
<213> Homo sapiens

<400> 24
Met Asp Cys Gln Glu Asn Glu Tyr Trp Asp Gln Trp Gly Arg Cys Val 
1               5                   10                  15      


Thr Cys Gln Arg Cys Gly Pro Gly Gln Glu Leu Ser Lys Asp Cys Gly 
            20                  25                  30          


Tyr Gly Glu Gly Gly Asp Ala Tyr Cys Thr Ala Cys Pro Pro Arg Arg 
        35                  40                  45              


Tyr Lys Ser Ser Trp Gly His His Arg Cys Gln Ser Cys Ile Thr Cys 
    50                  55                  60                  


Ala Val Ile Asn Arg Val Gln Lys Val Asn Cys Thr Ala Thr Ser Asn 
65                  70                  75                  80  


Ala Val Cys Gly Asp Cys Leu Pro Arg Phe Tyr Arg Lys Thr Arg Ile 
                85                  90                  95      


Gly Gly Leu Gln Asp Gln Glu Cys Ile Pro Cys Thr Lys Gln Thr Pro 
            100                 105                 110         


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


Thr Pro Thr Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser 
    130                 135                 140                 


Ser Leu Leu Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu 
145                 150                 155                 160 


Tyr Cys Lys Gln Phe Phe Asn Arg His Cys Gln Arg Val Ala Gly Gly 
                165                 170                 175     


Leu Leu Gln Phe Glu Ala Asp Lys Thr Ala Lys Glu Glu Ser Leu Phe 
            180                 185                 190         


Pro Val Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val Ser Glu 
        195                 200                 205             


Asn Ile Phe Gln Thr Gln Pro Leu Asn Pro Ile Leu Glu Asp Asp Cys 
    210                 215                 220                 


Ser Ser Thr Ser Gly Phe Pro Thr Gln Glu Ser Phe Thr Met Ala Ser 
225                 230                 235                 240 


Cys Thr Ser Glu Ser His Ser His Trp Val His Ser Pro Ile Glu Cys 
                245                 250                 255     


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


Ala Glu Thr Leu Gly Gly Asn Thr Val Glu Ser Thr Gly Asp Arg Leu 
        275                 280                 285             


Glu Leu Asn Val Pro Phe Glu Val Pro Ser Pro 
    290                 295                 


<210> 25
<211> 297
<212> PRT
<213> Homo sapiens

<400> 25
Met Asp Cys Gln Glu Asn Glu Tyr Trp Asp Gln Trp Gly Arg Cys Val 
1               5                   10                  15      


Thr Cys Gln Arg Cys Gly Pro Gly Gln Glu Leu Ser Lys Asp Cys Gly 
            20                  25                  30          


Tyr Gly Glu Gly Gly Asp Ala Tyr Cys Thr Ala Cys Pro Pro Arg Arg 
        35                  40                  45              


Tyr Lys Ser Ser Trp Gly His His Arg Cys Gln Ser Cys Ile Thr Cys 
    50                  55                  60                  


Ala Val Ile Asn Arg Val Gln Lys Val Asn Cys Thr Ala Thr Ser Asn 
65                  70                  75                  80  


Ala Val Cys Gly Asp Cys Leu Pro Arg Phe Tyr Arg Lys Thr Arg Ile 
                85                  90                  95      


Gly Gly Leu Gln Asp Gln Glu Cys Ile Pro Cys Thr Lys Gln Thr Pro 
            100                 105                 110         


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


Thr Pro Thr Val Pro Pro Gln Glu Ala Thr Leu Val Ala Leu Val Ser 
    130                 135                 140                 


Ser Leu Leu Val Val Phe Thr Leu Ala Phe Leu Gly Leu Phe Phe Leu 
145                 150                 155                 160 


Tyr Cys Lys Gln Phe Phe Asn Arg His Cys Gln Arg Gly Gly Leu Leu 
                165                 170                 175     


Gln Phe Glu Ala Asp Lys Thr Ala Lys Glu Glu Ser Leu Phe Pro Val 
            180                 185                 190         


Pro Pro Ser Lys Glu Thr Ser Ala Glu Ser Gln Val Ser Glu Asn Ile 
        195                 200                 205             


Phe Gln Thr Gln Pro Leu Asn Pro Ile Leu Glu Asp Asp Cys Ser Ser 
    210                 215                 220                 


Thr Ser Gly Phe Pro Thr Gln Glu Ser Phe Thr Met Ala Ser Cys Thr 
225                 230                 235                 240 


Ser Glu Ser His Ser His Trp Val His Ser Pro Ile Glu Cys Thr Glu 
                245                 250                 255     


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


Thr Leu Gly Gly Asn Thr Val Glu Ser Thr Gly Asp Arg Leu Glu Leu 
        275                 280                 285             


Asn Val Pro Phe Glu Val Pro Ser Pro 
    290                 295         


<210> 26
<211> 134
<212> PRT
<213> Homo sapiens

<400> 26
Met Asp Pro Gln Thr Ala Pro Ser Arg Ala Leu Leu Leu Leu Leu Phe 
1               5                   10                  15      


Leu His Leu Ala Phe Leu Gly Gly Arg Ser His Pro Leu Gly Ser Pro 
            20                  25                  30          


Gly Ser Ala Ser Asp Leu Glu Thr Ser Gly Leu Gln Glu Gln Arg Asn 
        35                  40                  45              


His Leu Gln Gly Lys Leu Ser Glu Leu Gln Val Glu Gln Thr Ser Leu 
    50                  55                  60                  


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


Glu Val Ala Thr Glu Gly Ile Arg Gly His Arg Lys Met Val Leu Tyr 
                85                  90                  95      


Thr Leu Arg Ala Pro Arg Ser Pro Lys Met Val Gln Gly Ser Gly Cys 
            100                 105                 110         


Phe Gly Arg Lys Met Asp Arg Ile Ser Ser Ser Ser Gly Leu Gly Cys 
        115                 120                 125             


Lys Val Leu Arg Arg His 
    130                 


