                               SEQUENCE LISTING

<110> MODERNATX, INC.
 
<120> MODIFIED MRNA ENCODING A PROPIONYL-COA CARBOXYLASE AND USES 
      THEREOF

<130> 45817-0030WO1

<140> PCT/US2018/043089
<141> 2018-07-20

<150> 62/535,289
<151> 2017-07-21

<160> 13    

<170> PatentIn version 3.5

<210> 1
<211> 728
<212> PRT
<213> Homo sapiens

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


Arg Gly Arg Trp Pro Pro Gln Gln Leu Met Leu Ser Ala Ala Leu Arg 
            20                  25                  30          


Thr Leu Lys His Val Leu Tyr Tyr Ser Arg Gln Cys Leu Met Val Ser 
        35                  40                  45              


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


Lys Ile Leu Val Ala Asn Arg Gly Glu Ile Ala Cys Arg Val Ile Arg 
65                  70                  75                  80  


Thr Cys Lys Lys Met Gly Ile Lys Thr Val Ala Ile His Ser Asp Val 
                85                  90                  95      


Asp Ala Ser Ser Val His Val Lys Met Ala Asp Glu Ala Val Cys Val 
            100                 105                 110         


Gly Pro Ala Pro Thr Ser Lys Ser Tyr Leu Asn Met Asp Ala Ile Met 
        115                 120                 125             


Glu Ala Ile Lys Lys Thr Arg Ala Gln Ala Val His Pro Gly Tyr Gly 
    130                 135                 140                 


Phe Leu Ser Glu Asn Lys Glu Phe Ala Arg Cys Leu Ala Ala Glu Asp 
145                 150                 155                 160 


Val Val Phe Ile Gly Pro Asp Thr His Ala Ile Gln Ala Met Gly Asp 
                165                 170                 175     


Lys Ile Glu Ser Lys Leu Leu Ala Lys Lys Ala Glu Val Asn Thr Ile 
            180                 185                 190         


Pro Gly Phe Asp Gly Val Val Lys Asp Ala Glu Glu Ala Val Arg Ile 
        195                 200                 205             


Ala Arg Glu Ile Gly Tyr Pro Val Met Ile Lys Ala Ser Ala Gly Gly 
    210                 215                 220                 


Gly Gly Lys Gly Met Arg Ile Ala Trp Asp Asp Glu Glu Thr Arg Asp 
225                 230                 235                 240 


Gly Phe Arg Leu Ser Ser Gln Glu Ala Ala Ser Ser Phe Gly Asp Asp 
                245                 250                 255     


Arg Leu Leu Ile Glu Lys Phe Ile Asp Asn Pro Arg His Ile Glu Ile 
            260                 265                 270         


Gln Val Leu Gly Asp Lys His Gly Asn Ala Leu Trp Leu Asn Glu Arg 
        275                 280                 285             


Glu Cys Ser Ile Gln Arg Arg Asn Gln Lys Val Val Glu Glu Ala Pro 
    290                 295                 300                 


Ser Ile Phe Leu Asp Ala Glu Thr Arg Arg Ala Met Gly Glu Gln Ala 
305                 310                 315                 320 


Val Ala Leu Ala Arg Ala Val Lys Tyr Ser Ser Ala Gly Thr Val Glu 
                325                 330                 335     


Phe Leu Val Asp Ser Lys Lys Asn Phe Tyr Phe Leu Glu Met Asn Thr 
            340                 345                 350         


Arg Leu Gln Val Glu His Pro Val Thr Glu Cys Ile Thr Gly Leu Asp 
        355                 360                 365             


Leu Val Gln Glu Met Ile Arg Val Ala Lys Gly Tyr Pro Leu Arg His 
    370                 375                 380                 


Lys Gln Ala Asp Ile Arg Ile Asn Gly Trp Ala Val Glu Cys Arg Val 
385                 390                 395                 400 


Tyr Ala Glu Asp Pro Tyr Lys Ser Phe Gly Leu Pro Ser Ile Gly Arg 
                405                 410                 415     


Leu Ser Gln Tyr Gln Glu Pro Leu His Leu Pro Gly Val Arg Val Asp 
            420                 425                 430         


Ser Gly Ile Gln Pro Gly Ser Asp Ile Ser Ile Tyr Tyr Asp Pro Met 
        435                 440                 445             


Ile Ser Lys Leu Ile Thr Tyr Gly Ser Asp Arg Thr Glu Ala Leu Lys 
    450                 455                 460                 


Arg Met Ala Asp Ala Leu Asp Asn Tyr Val Ile Arg Gly Val Thr His 
465                 470                 475                 480 


Asn Ile Ala Leu Leu Arg Glu Val Ile Ile Asn Ser Arg Phe Val Lys 
                485                 490                 495     


Gly Asp Ile Ser Thr Lys Phe Leu Ser Asp Val Tyr Pro Asp Gly Phe 
            500                 505                 510         


Lys Gly His Met Leu Thr Lys Ser Glu Lys Asn Gln Leu Leu Ala Ile 
        515                 520                 525             


Ala Ser Ser Leu Phe Val Ala Phe Gln Leu Arg Ala Gln His Phe Gln 
    530                 535                 540                 


Glu Asn Ser Arg Met Pro Val Ile Lys Pro Asp Ile Ala Asn Trp Glu 
545                 550                 555                 560 


Leu Ser Val Lys Leu His Asp Lys Val His Thr Val Val Ala Ser Asn 
                565                 570                 575     


Asn Gly Ser Val Phe Ser Val Glu Val Asp Gly Ser Lys Leu Asn Val 
            580                 585                 590         


Thr Ser Thr Trp Asn Leu Ala Ser Pro Leu Leu Ser Val Ser Val Asp 
        595                 600                 605             


Gly Thr Gln Arg Thr Val Gln Cys Leu Ser Arg Glu Ala Gly Gly Asn 
    610                 615                 620                 


Met Ser Ile Gln Phe Leu Gly Thr Val Tyr Lys Val Asn Ile Leu Thr 
625                 630                 635                 640 


Arg Leu Ala Ala Glu Leu Asn Lys Phe Met Leu Glu Lys Val Thr Glu 
                645                 650                 655     


Asp Thr Ser Ser Val Leu Arg Ser Pro Met Pro Gly Val Val Val Ala 
            660                 665                 670         


Val Ser Val Lys Pro Gly Asp Ala Val Ala Glu Gly Gln Glu Ile Cys 
        675                 680                 685             


Val Ile Glu Ala Met Lys Met Gln Asn Ser Met Thr Ala Gly Lys Thr 
    690                 695                 700                 


Gly Thr Val Lys Ser Val His Cys Gln Ala Gly Asp Thr Val Gly Glu 
705                 710                 715                 720 


Gly Asp Leu Leu Val Glu Leu Glu 
                725             


<210> 2
<211> 702
<212> PRT
<213> Homo sapiens

<400> 2
Met Ala Gly Phe Trp Val Gly Thr Ala Pro Leu Val Ala Ala Gly Arg 
1               5                   10                  15      


Arg Gly Arg Trp Pro Pro Gln Gln Leu Met Leu Ser Ala Ala Leu Arg 
            20                  25                  30          


Thr Leu Lys Thr Phe Asp Lys Ile Leu Val Ala Asn Arg Gly Glu Ile 
        35                  40                  45              


Ala Cys Arg Val Ile Arg Thr Cys Lys Lys Met Gly Ile Lys Thr Val 
    50                  55                  60                  


Ala Ile His Ser Asp Val Asp Ala Ser Ser Val His Val Lys Met Ala 
65                  70                  75                  80  


Asp Glu Ala Val Cys Val Gly Pro Ala Pro Thr Ser Lys Ser Tyr Leu 
                85                  90                  95      


Asn Met Asp Ala Ile Met Glu Ala Ile Lys Lys Thr Arg Ala Gln Ala 
            100                 105                 110         


Val His Pro Gly Tyr Gly Phe Leu Ser Glu Asn Lys Glu Phe Ala Arg 
        115                 120                 125             


Cys Leu Ala Ala Glu Asp Val Val Phe Ile Gly Pro Asp Thr His Ala 
    130                 135                 140                 


Ile Gln Ala Met Gly Asp Lys Ile Glu Ser Lys Leu Leu Ala Lys Lys 
145                 150                 155                 160 


Ala Glu Val Asn Thr Ile Pro Gly Phe Asp Gly Val Val Lys Asp Ala 
                165                 170                 175     


Glu Glu Ala Val Arg Ile Ala Arg Glu Ile Gly Tyr Pro Val Met Ile 
            180                 185                 190         


Lys Ala Ser Ala Gly Gly Gly Gly Lys Gly Met Arg Ile Ala Trp Asp 
        195                 200                 205             


Asp Glu Glu Thr Arg Asp Gly Phe Arg Leu Ser Ser Gln Glu Ala Ala 
    210                 215                 220                 


Ser Ser Phe Gly Asp Asp Arg Leu Leu Ile Glu Lys Phe Ile Asp Asn 
225                 230                 235                 240 


Pro Arg His Ile Glu Ile Gln Val Leu Gly Asp Lys His Gly Asn Ala 
                245                 250                 255     


Leu Trp Leu Asn Glu Arg Glu Cys Ser Ile Gln Arg Arg Asn Gln Lys 
            260                 265                 270         


Val Val Glu Glu Ala Pro Ser Ile Phe Leu Asp Ala Glu Thr Arg Arg 
        275                 280                 285             


Ala Met Gly Glu Gln Ala Val Ala Leu Ala Arg Ala Val Lys Tyr Ser 
    290                 295                 300                 


Ser Ala Gly Thr Val Glu Phe Leu Val Asp Ser Lys Lys Asn Phe Tyr 
305                 310                 315                 320 


Phe Leu Glu Met Asn Thr Arg Leu Gln Val Glu His Pro Val Thr Glu 
                325                 330                 335     


Cys Ile Thr Gly Leu Asp Leu Val Gln Glu Met Ile Arg Val Ala Lys 
            340                 345                 350         


Gly Tyr Pro Leu Arg His Lys Gln Ala Asp Ile Arg Ile Asn Gly Trp 
        355                 360                 365             


Ala Val Glu Cys Arg Val Tyr Ala Glu Asp Pro Tyr Lys Ser Phe Gly 
    370                 375                 380                 


Leu Pro Ser Ile Gly Arg Leu Ser Gln Tyr Gln Glu Pro Leu His Leu 
385                 390                 395                 400 


Pro Gly Val Arg Val Asp Ser Gly Ile Gln Pro Gly Ser Asp Ile Ser 
                405                 410                 415     


Ile Tyr Tyr Asp Pro Met Ile Ser Lys Leu Ile Thr Tyr Gly Ser Asp 
            420                 425                 430         


Arg Thr Glu Ala Leu Lys Arg Met Ala Asp Ala Leu Asp Asn Tyr Val 
        435                 440                 445             


Ile Arg Gly Val Thr His Asn Ile Ala Leu Leu Arg Glu Val Ile Ile 
    450                 455                 460                 


Asn Ser Arg Phe Val Lys Gly Asp Ile Ser Thr Lys Phe Leu Ser Asp 
465                 470                 475                 480 


Val Tyr Pro Asp Gly Phe Lys Gly His Met Leu Thr Lys Ser Glu Lys 
                485                 490                 495     


Asn Gln Leu Leu Ala Ile Ala Ser Ser Leu Phe Val Ala Phe Gln Leu 
            500                 505                 510         


Arg Ala Gln His Phe Gln Glu Asn Ser Arg Met Pro Val Ile Lys Pro 
        515                 520                 525             


Asp Ile Ala Asn Trp Glu Leu Ser Val Lys Leu His Asp Lys Val His 
    530                 535                 540                 


Thr Val Val Ala Ser Asn Asn Gly Ser Val Phe Ser Val Glu Val Asp 
545                 550                 555                 560 


Gly Ser Lys Leu Asn Val Thr Ser Thr Trp Asn Leu Ala Ser Pro Leu 
                565                 570                 575     


Leu Ser Val Ser Val Asp Gly Thr Gln Arg Thr Val Gln Cys Leu Ser 
            580                 585                 590         


Arg Glu Ala Gly Gly Asn Met Ser Ile Gln Phe Leu Gly Thr Val Tyr 
        595                 600                 605             


Lys Val Asn Ile Leu Thr Arg Leu Ala Ala Glu Leu Asn Lys Phe Met 
    610                 615                 620                 


Leu Glu Lys Val Thr Glu Asp Thr Ser Ser Val Leu Arg Ser Pro Met 
625                 630                 635                 640 


Pro Gly Val Val Val Ala Val Ser Val Lys Pro Gly Asp Ala Val Ala 
                645                 650                 655     


Glu Gly Gln Glu Ile Cys Val Ile Glu Ala Met Lys Met Gln Asn Ser 
            660                 665                 670         


Met Thr Ala Gly Lys Thr Gly Thr Val Lys Ser Val His Cys Gln Ala 
        675                 680                 685             


Gly Asp Thr Val Gly Glu Gly Asp Leu Leu Val Glu Leu Glu 
    690                 695                 700         


<210> 3
<211> 681
<212> PRT
<213> Homo sapiens

<400> 3
Met Ala Gly Phe Trp Val Gly Thr Ala Pro Leu Val Ala Ala Gly Arg 
1               5                   10                  15      


Arg Gly Arg Trp Pro Pro Gln Gln Leu Met Leu Ser Ala Ala Leu Arg 
            20                  25                  30          


Thr Leu Lys His Val Leu Tyr Tyr Ser Arg Gln Cys Leu Met Val Ser 
        35                  40                  45              


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


Lys Ile Leu Val Ala Asn Arg Gly Glu Ile Ala Cys Arg Val Ile Arg 
65                  70                  75                  80  


Thr Cys Lys Lys Met Gly Ile Lys Thr Val Ala Ile His Ser Asp Val 
                85                  90                  95      


Asp Ala Ser Ser Val His Val Lys Met Ala Asp Glu Ala Val Cys Val 
            100                 105                 110         


Gly Pro Ala Pro Thr Ser Lys Ser Tyr Leu Asn Met Asp Ala Ile Met 
        115                 120                 125             


Glu Ala Ile Lys Lys Thr Arg Ala Gln Ala Val His Pro Gly Tyr Gly 
    130                 135                 140                 


Phe Leu Ser Glu Asn Lys Glu Phe Ala Arg Cys Leu Ala Ala Glu Asp 
145                 150                 155                 160 


Val Val Phe Ile Gly Pro Asp Thr His Ala Ile Gln Ala Met Gly Asp 
                165                 170                 175     


Lys Ile Glu Ser Lys Leu Leu Ala Lys Lys Ala Glu Val Asn Thr Ile 
            180                 185                 190         


Pro Gly Phe Asp Gly Val Val Lys Asp Ala Glu Glu Ala Val Arg Ile 
        195                 200                 205             


Ala Arg Glu Ile Gly Tyr Pro Val Met Ile Lys Ala Ser Ala Gly Gly 
    210                 215                 220                 


Gly Gly Lys Gly Met Arg Ile Ala Trp Asp Asp Glu Glu Thr Arg Asp 
225                 230                 235                 240 


Gly Phe Arg Leu Ser Ser Gln Glu Ala Ala Ser Ser Phe Gly Asp Asp 
                245                 250                 255     


Arg Leu Leu Ile Glu Lys Phe Ile Asp Asn Pro Arg His Ile Glu Ile 
            260                 265                 270         


Gln Val Leu Gly Asp Lys His Gly Asn Ala Leu Trp Leu Asn Glu Arg 
        275                 280                 285             


Glu Cys Ser Ile Gln Arg Arg Asn Gln Lys Val Val Glu Glu Ala Pro 
    290                 295                 300                 


Ser Ile Phe Leu Asp Ala Glu Thr Arg Arg Ala Met Gly Glu Gln Ala 
305                 310                 315                 320 


Val Ala Leu Ala Arg Ala Val Lys Tyr Ser Ser Ala Gly Thr Val Glu 
                325                 330                 335     


Phe Leu Val Asp Ser Lys Lys Asn Phe Tyr Phe Leu Glu Met Asn Thr 
            340                 345                 350         


Arg Leu Gln Val Glu His Pro Val Thr Glu Cys Ile Thr Gly Leu Asp 
        355                 360                 365             


Leu Val Gln Glu Met Ile Arg Val Ala Lys Gly Tyr Pro Leu Arg His 
    370                 375                 380                 


Lys Gln Ala Asp Ile Arg Ile Asn Gly Trp Ala Val Glu Cys Arg Val 
385                 390                 395                 400 


Tyr Ala Glu Asp Pro Tyr Lys Ser Phe Gly Leu Pro Ser Ile Gly Arg 
                405                 410                 415     


Leu Ser Gln Tyr Gln Glu Pro Leu His Leu Pro Gly Val Arg Val Asp 
            420                 425                 430         


Ser Gly Ile Gln Pro Gly Ser Asp Ile Ser Ile Tyr Tyr Asp Pro Met 
        435                 440                 445             


Ile Ser Lys Leu Ile Thr Tyr Gly Ser Asp Arg Thr Glu Ala Leu Lys 
    450                 455                 460                 


Arg Met Ala Asp Ala Leu Asp Asn Tyr Val Ile Arg Gly Val Thr His 
465                 470                 475                 480 


Asn Ile Ala Leu Leu Arg Glu Val Ile Ile Asn Ser Arg Phe Val Lys 
                485                 490                 495     


Gly Asp Ile Ser Thr Lys Phe Leu Ser Asp Val Tyr Pro Asp Gly Phe 
            500                 505                 510         


Lys Gly His Met Leu Thr Lys Ser Glu Lys Asn Gln Leu Leu Ala Ile 
        515                 520                 525             


Ala Ser Ser Leu Phe Val Ala Phe Gln Leu Arg Ala Gln His Phe Gln 
    530                 535                 540                 


Glu Asn Ser Arg Met Pro Val Ile Lys Pro Asp Ile Ala Asn Trp Glu 
545                 550                 555                 560 


Leu Ser Val Lys Leu His Asp Lys Val His Thr Val Val Ala Ser Asn 
                565                 570                 575     


Asn Gly Ser Val Phe Ser Val Glu Val Asp Gly Ser Lys Leu Asn Val 
            580                 585                 590         


Thr Ser Thr Trp Asn Leu Ala Ser Pro Leu Leu Ser Val Ser Val Asp 
        595                 600                 605             


Gly Thr Gln Arg Thr Val Gln Cys Leu Ser Arg Glu Ala Gly Gly Asn 
    610                 615                 620                 


Met Ser Ile Gln Phe Leu Gly Thr Val Val Ala Glu Gly Gln Glu Ile 
625                 630                 635                 640 


Cys Val Ile Glu Ala Met Lys Met Gln Asn Ser Met Thr Ala Gly Lys 
                645                 650                 655     


Thr Gly Thr Val Lys Ser Val His Cys Gln Ala Gly Asp Thr Val Gly 
            660                 665                 670         


Glu Gly Asp Leu Leu Val Glu Leu Glu 
        675                 680     


<210> 4
<211> 539
<212> PRT
<213> Homo sapiens

<400> 4
Met Ala Ala Ala Leu Arg Val Ala Ala Val Gly Ala Arg Leu Ser Val 
1               5                   10                  15      


Leu Ala Ser Gly Leu Arg Ala Ala Val Arg Ser Leu Cys Ser Gln Ala 
            20                  25                  30          


Thr Ser Val Asn Glu Arg Ile Glu Asn Lys Arg Arg Thr Ala Leu Leu 
        35                  40                  45              


Gly Gly Gly Gln Arg Arg Ile Asp Ala Gln His Lys Arg Gly Lys Leu 
    50                  55                  60                  


Thr Ala Arg Glu Arg Ile Ser Leu Leu Leu Asp Pro Gly Ser Phe Val 
65                  70                  75                  80  


Glu Ser Asp Met Phe Val Glu His Arg Cys Ala Asp Phe Gly Met Ala 
                85                  90                  95      


Ala Asp Lys Asn Lys Phe Pro Gly Asp Ser Val Val Thr Gly Arg Gly 
            100                 105                 110         


Arg Ile Asn Gly Arg Leu Val Tyr Val Phe Ser Gln Asp Phe Thr Val 
        115                 120                 125             


Phe Gly Gly Ser Leu Ser Gly Ala His Ala Gln Lys Ile Cys Lys Ile 
    130                 135                 140                 


Met Asp Gln Ala Ile Thr Val Gly Ala Pro Val Ile Gly Leu Asn Asp 
145                 150                 155                 160 


Ser Gly Gly Ala Arg Ile Gln Glu Gly Val Glu Ser Leu Ala Gly Tyr 
                165                 170                 175     


Ala Asp Ile Phe Leu Arg Asn Val Thr Ala Ser Gly Val Ile Pro Gln 
            180                 185                 190         


Ile Ser Leu Ile Met Gly Pro Cys Ala Gly Gly Ala Val Tyr Ser Pro 
        195                 200                 205             


Ala Leu Thr Asp Phe Thr Phe Met Val Lys Asp Thr Ser Tyr Leu Phe 
    210                 215                 220                 


Ile Thr Gly Pro Asp Val Val Lys Ser Val Thr Asn Glu Asp Val Thr 
225                 230                 235                 240 


Gln Glu Glu Leu Gly Gly Ala Lys Thr His Thr Thr Met Ser Gly Val 
                245                 250                 255     


Ala His Arg Ala Phe Glu Asn Asp Val Asp Ala Leu Cys Asn Leu Arg 
            260                 265                 270         


Asp Phe Phe Asn Tyr Leu Pro Leu Ser Ser Gln Asp Pro Ala Pro Val 
        275                 280                 285             


Arg Glu Cys His Asp Pro Ser Asp Arg Leu Val Pro Glu Leu Asp Thr 
    290                 295                 300                 


Ile Val Pro Leu Glu Ser Thr Lys Ala Tyr Asn Met Val Asp Ile Ile 
305                 310                 315                 320 


His Ser Val Val Asp Glu Arg Glu Phe Phe Glu Ile Met Pro Asn Tyr 
                325                 330                 335     


Ala Lys Asn Ile Ile Val Gly Phe Ala Arg Met Asn Gly Arg Thr Val 
            340                 345                 350         


Gly Ile Val Gly Asn Gln Pro Lys Val Ala Ser Gly Cys Leu Asp Ile 
        355                 360                 365             


Asn Ser Ser Val Lys Gly Ala Arg Phe Val Arg Phe Cys Asp Ala Phe 
    370                 375                 380                 


Asn Ile Pro Leu Ile Thr Phe Val Asp Val Pro Gly Phe Leu Pro Gly 
385                 390                 395                 400 


Thr Ala Gln Glu Tyr Gly Gly Ile Ile Arg His Gly Ala Lys Leu Leu 
                405                 410                 415     


Tyr Ala Phe Ala Glu Ala Thr Val Pro Lys Val Thr Val Ile Thr Arg 
            420                 425                 430         


Lys Ala Tyr Gly Gly Ala Tyr Asp Val Met Ser Ser Lys His Leu Cys 
        435                 440                 445             


Gly Asp Thr Asn Tyr Ala Trp Pro Thr Ala Glu Ile Ala Val Met Gly 
    450                 455                 460                 


Ala Lys Gly Ala Val Glu Ile Ile Phe Lys Gly His Glu Asn Val Glu 
465                 470                 475                 480 


Ala Ala Gln Ala Glu Tyr Ile Glu Lys Phe Ala Asn Pro Phe Pro Ala 
                485                 490                 495     


Ala Val Arg Gly Phe Val Asp Asp Ile Ile Gln Pro Ser Ser Thr Arg 
            500                 505                 510         


Ala Arg Ile Cys Cys Asp Leu Asp Val Leu Ala Ser Lys Lys Val Gln 
        515                 520                 525             


Arg Pro Trp Arg Lys His Ala Asn Ile Pro Leu 
    530                 535                 


<210> 5
<211> 559
<212> PRT
<213> Homo sapiens

<400> 5
Met Ala Ala Ala Leu Arg Val Ala Ala Val Gly Ala Arg Leu Ser Val 
1               5                   10                  15      


Leu Ala Ser Gly Leu Arg Ala Ala Val Arg Ser Leu Cys Ser Gln Ala 
            20                  25                  30          


Thr Ser Val Asn Glu Arg Ile Glu Asn Lys Arg Arg Thr Ala Leu Leu 
        35                  40                  45              


Gly Gly Gly Gln Arg Arg Ile Asp Ala Gln His Lys Arg Gly Lys Leu 
    50                  55                  60                  


Thr Ala Arg Glu Arg Ile Ser Leu Leu Leu Asp Pro Gly Ser Phe Val 
65                  70                  75                  80  


Glu Ser Asp Met Phe Val Glu His Arg Cys Ala Asp Phe Gly Met Ala 
                85                  90                  95      


Ala Asp Lys Asn Lys Phe Pro Gly Asp Ser Val Val Thr Gly Arg Gly 
            100                 105                 110         


Arg Ile Asn Gly Arg Leu Val Tyr Val Phe Ser Gln Gln Ile Ile Gly 
        115                 120                 125             


Trp Ala Gln Trp Leu Pro Leu Val Ile Ser Ala Leu Trp Glu Ala Glu 
    130                 135                 140                 


Asp Phe Thr Val Phe Gly Gly Ser Leu Ser Gly Ala His Ala Gln Lys 
145                 150                 155                 160 


Ile Cys Lys Ile Met Asp Gln Ala Ile Thr Val Gly Ala Pro Val Ile 
                165                 170                 175     


Gly Leu Asn Asp Ser Gly Gly Ala Arg Ile Gln Glu Gly Val Glu Ser 
            180                 185                 190         


Leu Ala Gly Tyr Ala Asp Ile Phe Leu Arg Asn Val Thr Ala Ser Gly 
        195                 200                 205             


Val Ile Pro Gln Ile Ser Leu Ile Met Gly Pro Cys Ala Gly Gly Ala 
    210                 215                 220                 


Val Tyr Ser Pro Ala Leu Thr Asp Phe Thr Phe Met Val Lys Asp Thr 
225                 230                 235                 240 


Ser Tyr Leu Phe Ile Thr Gly Pro Asp Val Val Lys Ser Val Thr Asn 
                245                 250                 255     


Glu Asp Val Thr Gln Glu Glu Leu Gly Gly Ala Lys Thr His Thr Thr 
            260                 265                 270         


Met Ser Gly Val Ala His Arg Ala Phe Glu Asn Asp Val Asp Ala Leu 
        275                 280                 285             


Cys Asn Leu Arg Asp Phe Phe Asn Tyr Leu Pro Leu Ser Ser Gln Asp 
    290                 295                 300                 


Pro Ala Pro Val Arg Glu Cys His Asp Pro Ser Asp Arg Leu Val Pro 
305                 310                 315                 320 


Glu Leu Asp Thr Ile Val Pro Leu Glu Ser Thr Lys Ala Tyr Asn Met 
                325                 330                 335     


Val Asp Ile Ile His Ser Val Val Asp Glu Arg Glu Phe Phe Glu Ile 
            340                 345                 350         


Met Pro Asn Tyr Ala Lys Asn Ile Ile Val Gly Phe Ala Arg Met Asn 
        355                 360                 365             


Gly Arg Thr Val Gly Ile Val Gly Asn Gln Pro Lys Val Ala Ser Gly 
    370                 375                 380                 


Cys Leu Asp Ile Asn Ser Ser Val Lys Gly Ala Arg Phe Val Arg Phe 
385                 390                 395                 400 


Cys Asp Ala Phe Asn Ile Pro Leu Ile Thr Phe Val Asp Val Pro Gly 
                405                 410                 415     


Phe Leu Pro Gly Thr Ala Gln Glu Tyr Gly Gly Ile Ile Arg His Gly 
            420                 425                 430         


Ala Lys Leu Leu Tyr Ala Phe Ala Glu Ala Thr Val Pro Lys Val Thr 
        435                 440                 445             


Val Ile Thr Arg Lys Ala Tyr Gly Gly Ala Tyr Asp Val Met Ser Ser 
    450                 455                 460                 


Lys His Leu Cys Gly Asp Thr Asn Tyr Ala Trp Pro Thr Ala Glu Ile 
465                 470                 475                 480 


Ala Val Met Gly Ala Lys Gly Ala Val Glu Ile Ile Phe Lys Gly His 
                485                 490                 495     


Glu Asn Val Glu Ala Ala Gln Ala Glu Tyr Ile Glu Lys Phe Ala Asn 
            500                 505                 510         


Pro Phe Pro Ala Ala Val Arg Gly Phe Val Asp Asp Ile Ile Gln Pro 
        515                 520                 525             


Ser Ser Thr Arg Ala Arg Ile Cys Cys Asp Leu Asp Val Leu Ala Ser 
    530                 535                 540                 


Lys Lys Val Gln Arg Pro Trp Arg Lys His Ala Asn Ile Pro Leu 
545                 550                 555                 


<210> 6
<211> 724
<212> PRT
<213> Mus musculus

<400> 6
Met Ala Gly Gln Trp Val Arg Thr Val Ala Leu Leu Ala Ala Arg Arg 
1               5                   10                  15      


His Trp Arg Arg Ser Ser Gln Gln Gln Leu Leu Gly Thr Leu Lys His 
            20                  25                  30          


Ala Pro Val Tyr Ser Tyr Gln Cys Leu Val Val Ser Arg Ser Leu Ser 
        35                  40                  45              


Ser Val Glu Tyr Glu Pro Lys Glu Lys Thr Phe Asp Lys Ile Leu Ile 
    50                  55                  60                  


Ala Asn Arg Gly Glu Ile Ala Cys Arg Val Ile Lys Thr Cys Lys Lys 
65                  70                  75                  80  


Met Gly Ile Lys Thr Val Ala Ile His Ser Asp Val Asp Ala Ser Ser 
                85                  90                  95      


Val His Val Lys Met Ala Asp Glu Ala Val Cys Val Gly Pro Ala Pro 
            100                 105                 110         


Thr Ser Lys Ser Tyr Leu Asn Met Asp Ala Ile Met Glu Ala Ile Lys 
        115                 120                 125             


Lys Thr Arg Ala Gln Ala Val His Pro Gly Tyr Gly Phe Leu Ser Glu 
    130                 135                 140                 


Asn Lys Glu Phe Ala Lys Arg Leu Ala Ala Glu Asp Val Thr Phe Ile 
145                 150                 155                 160 


Gly Pro Asp Thr His Ala Ile Gln Ala Met Gly Asp Lys Ile Glu Ser 
                165                 170                 175     


Lys Leu Leu Ala Lys Arg Ala Lys Val Asn Thr Ile Pro Gly Phe Asp 
            180                 185                 190         


Gly Val Val Lys Asp Ala Asp Glu Ala Val Arg Ile Ala Arg Glu Ile 
        195                 200                 205             


Gly Tyr Pro Val Met Ile Lys Ala Ser Ala Gly Gly Gly Gly Lys Gly 
    210                 215                 220                 


Met Arg Ile Ala Trp Asp Asp Glu Glu Thr Arg Asp Gly Phe Arg Phe 
225                 230                 235                 240 


Ser Ser Gln Glu Ala Ala Ser Ser Phe Gly Asp Asp Arg Leu Leu Ile 
                245                 250                 255     


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


Asp Lys His Gly Asn Ala Leu Trp Leu Asn Glu Arg Glu Cys Ser Ile 
        275                 280                 285             


Gln Arg Arg Asn Gln Lys Val Val Glu Glu Ala Pro Ser Ile Phe Leu 
    290                 295                 300                 


Asp Pro Glu Thr Arg Gln Ala Met Gly Glu Gln Ala Val Ala Leu Ala 
305                 310                 315                 320 


Lys Ala Val Lys Tyr Ser Ser Ala Gly Thr Val Glu Phe Leu Val Asp 
                325                 330                 335     


Ser Gln Lys Asn Phe Tyr Phe Leu Glu Met Asn Thr Arg Leu Gln Val 
            340                 345                 350         


Glu His Pro Val Thr Glu Cys Ile Thr Gly Leu Asp Leu Val Gln Glu 
        355                 360                 365             


Met Ile Leu Val Ala Lys Gly Tyr Pro Leu Arg His Lys Gln Glu Asp 
    370                 375                 380                 


Ile Pro Ile Ser Gly Trp Ala Val Glu Cys Arg Val Tyr Ala Glu Asp 
385                 390                 395                 400 


Pro Tyr Lys Ser Phe Gly Leu Pro Ser Ile Gly Arg Leu Ser Gln Tyr 
                405                 410                 415     


Gln Glu Pro Ile His Leu Pro Gly Val Arg Val Asp Ser Gly Ile Gln 
            420                 425                 430         


Pro Gly Ser Asp Ile Ser Ile Tyr Tyr Asp Pro Met Ile Ser Lys Leu 
        435                 440                 445             


Val Thr Tyr Gly Ser Asp Arg Ala Glu Ala Leu Lys Arg Met Glu Asp 
    450                 455                 460                 


Ala Leu Asp Asn Tyr Val Ile Arg Gly Val Thr His Asn Ile Pro Leu 
465                 470                 475                 480 


Leu Arg Glu Val Ile Ile Asn Thr Arg Phe Val Lys Gly Asp Ile Ser 
                485                 490                 495     


Thr Lys Phe Leu Ser Asp Val Tyr Pro Asp Gly Phe Lys Gly His Thr 
            500                 505                 510         


Leu Thr Leu Ser Glu Arg Asn Gln Leu Leu Ala Ile Ala Ser Ser Val 
        515                 520                 525             


Phe Val Ala Ser Gln Leu Arg Ala Gln Arg Phe Gln Glu His Ser Arg 
    530                 535                 540                 


Val Pro Val Ile Arg Pro Asp Val Ala Lys Trp Glu Leu Ser Val Lys 
545                 550                 555                 560 


Leu His Asp Glu Asp His Thr Val Val Ala Ser Asn Asn Gly Pro Ala 
                565                 570                 575     


Phe Thr Val Glu Val Asp Gly Ser Lys Leu Asn Val Thr Ser Thr Trp 
            580                 585                 590         


Asn Leu Ala Ser Pro Leu Leu Ser Val Asn Val Asp Gly Thr Gln Arg 
        595                 600                 605             


Thr Val Gln Cys Leu Ser Arg Glu Ala Gly Gly Asn Met Ser Ile Gln 
    610                 615                 620                 


Phe Leu Gly Thr Val Tyr Lys Val His Ile Leu Thr Lys Leu Ala Ala 
625                 630                 635                 640 


Glu Leu Asn Lys Phe Met Leu Glu Lys Val Pro Lys Asp Thr Ser Ser 
                645                 650                 655     


Thr Leu Cys Ser Pro Met Pro Gly Val Val Val Ala Val Ser Val Lys 
            660                 665                 670         


Pro Gly Asp Met Val Ala Glu Gly Gln Glu Ile Cys Val Ile Glu Ala 
        675                 680                 685             


Met Lys Met Gln Asn Ser Met Thr Ala Gly Lys Met Gly Lys Val Lys 
    690                 695                 700                 


Leu Val His Cys Lys Ala Gly Asp Thr Val Gly Glu Gly Asp Leu Leu 
705                 710                 715                 720 


Val Glu Leu Glu 
                


<210> 7
<211> 541
<212> PRT
<213> Mus musculus

<400> 7
Met Ala Ala Ala Ile Arg Ile Arg Ala Val Ala Ala Gly Ala Arg Leu 
1               5                   10                  15      


Ser Val Leu Asn Cys Gly Leu Gly Ile Thr Thr Arg Gly Leu Cys Ser 
            20                  25                  30          


Gln Pro Val Ser Val Lys Glu Arg Ile Asp Asn Lys Arg His Ala Ala 
        35                  40                  45              


Leu Leu Gly Gly Gly Gln Arg Arg Ile Asp Ala Gln His Lys Arg Gly 
    50                  55                  60                  


Lys Leu Thr Ala Arg Glu Arg Ile Ser Leu Leu Leu Asp Pro Gly Ser 
65                  70                  75                  80  


Phe Met Glu Ser Asp Met Phe Val Glu His Arg Cys Ala Asp Phe Gly 
                85                  90                  95      


Met Ala Ala Asp Lys Asn Lys Phe Pro Gly Asp Ser Val Val Thr Gly 
            100                 105                 110         


Arg Gly Arg Ile Asn Gly Arg Leu Val Tyr Val Phe Ser Gln Asp Phe 
        115                 120                 125             


Thr Val Phe Gly Gly Ser Leu Ser Gly Ala His Ala Gln Lys Ile Cys 
    130                 135                 140                 


Lys Ile Met Asp Gln Ala Ile Thr Val Gly Ala Pro Val Ile Gly Leu 
145                 150                 155                 160 


Asn Asp Ser Gly Gly Ala Arg Ile Gln Glu Gly Val Glu Ser Leu Ala 
                165                 170                 175     


Gly Tyr Ala Asp Ile Phe Leu Arg Asn Val Thr Ala Ser Gly Val Ile 
            180                 185                 190         


Pro Gln Ile Ser Leu Ile Met Gly Pro Cys Ala Gly Gly Ala Val Tyr 
        195                 200                 205             


Ser Pro Ala Leu Thr Asp Phe Thr Phe Met Val Lys Asp Thr Ser Tyr 
    210                 215                 220                 


Leu Phe Ile Thr Gly Pro Glu Val Val Lys Ser Val Thr Asn Glu Asp 
225                 230                 235                 240 


Val Thr Gln Glu Gln Leu Gly Gly Ala Lys Thr His Thr Thr Val Ser 
                245                 250                 255     


Gly Val Ala His Arg Ala Phe Asp Asn Asp Val Asp Ala Leu Cys Asn 
            260                 265                 270         


Leu Arg Glu Phe Phe Asn Phe Leu Pro Leu Ser Ser Gln Asp Pro Ala 
        275                 280                 285             


Pro Ile Arg Glu Cys His Asp Pro Ser Asp Arg Leu Val Pro Glu Leu 
    290                 295                 300                 


Asp Thr Val Val Pro Leu Glu Ser Ser Lys Ala Tyr Asn Met Leu Asp 
305                 310                 315                 320 


Ile Ile His Ala Val Ile Asp Glu Arg Glu Phe Phe Glu Ile Met Pro 
                325                 330                 335     


Ser Tyr Ala Lys Asn Ile Val Val Gly Phe Ala Arg Met Asn Gly Arg 
            340                 345                 350         


Thr Val Gly Ile Val Gly Asn Gln Pro Asn Val Ala Ser Gly Cys Leu 
        355                 360                 365             


Asp Ile Asn Ser Ser Val Lys Gly Ala Arg Phe Val Arg Phe Cys Asp 
    370                 375                 380                 


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


Pro Gly Thr Ala Gln Glu Tyr Gly Gly Ile Ile Arg His Gly Ala Lys 
                405                 410                 415     


Leu Leu Tyr Ala Phe Ala Glu Ala Thr Val Pro Lys Ile Thr Val Ile 
            420                 425                 430         


Thr Arg Lys Ala Tyr Gly Gly Ala Tyr Asp Val Met Ser Ser Lys His 
        435                 440                 445             


Leu Leu Gly Asp Thr Asn Tyr Ala Trp Pro Thr Ala Glu Ile Ala Val 
    450                 455                 460                 


Met Gly Ala Lys Gly Ala Val Glu Ile Ile Phe Lys Gly His Gln Asp 
465                 470                 475                 480 


Val Glu Ala Ala Gln Ala Glu Tyr Val Glu Lys Phe Ala Asn Pro Phe 
                485                 490                 495     


Pro Ala Ala Val Arg Gly Phe Val Asp Asp Ile Ile Gln Pro Ser Ser 
            500                 505                 510         


Thr Arg Ala Arg Ile Cys Cys Asp Leu Glu Val Leu Ala Ser Lys Lys 
        515                 520                 525             


Val His Arg Pro Trp Arg Lys His Ala Asn Ile Pro Leu 
    530                 535                 540     


<210> 8
<211> 504
<212> PRT
<213> Mus musculus

<400> 8
Met Ala Ala Ala Ile Arg Ile Arg Ala Val Ala Ala Gly Ala Arg Leu 
1               5                   10                  15      


Ser Val Leu Asn Cys Gly Leu Gly Ile Thr Thr Arg Gly Leu Cys Ser 
            20                  25                  30          


Gln Pro Val Ser Val Lys Glu Arg Ile Asp Asn Lys Arg His Ala Ala 
        35                  40                  45              


Leu Leu Gly Gly Gly Gln Arg Arg Ile Asp Ala Gln His Lys Arg Gly 
    50                  55                  60                  


Lys Leu Thr Ala Arg Glu Arg Ile Ser Leu Leu Leu Asp Pro Gly Ser 
65                  70                  75                  80  


Phe Met Glu Ser Asp Met Phe Val Glu His Arg Cys Ala Asp Phe Gly 
                85                  90                  95      


Met Ala Ala Asp Lys Asn Lys Phe Pro Gly Asp Ser Val Val Thr Gly 
            100                 105                 110         


Arg Gly Arg Ile Asn Gly Arg Leu Val Tyr Val Phe Ser Gln Asp Phe 
        115                 120                 125             


Thr Val Phe Gly Gly Ser Leu Ser Gly Ala His Ala Gln Lys Ile Cys 
    130                 135                 140                 


Lys Ile Met Asp Gln Ala Ile Thr Val Gly Ala Pro Val Ile Gly Leu 
145                 150                 155                 160 


Asn Asp Ser Gly Gly Ala Arg Ile Gln Glu Gly Val Glu Ser Leu Ala 
                165                 170                 175     


Gly Tyr Ala Asp Ile Phe Leu Asp Thr Ser Tyr Leu Phe Ile Thr Gly 
            180                 185                 190         


Pro Glu Val Val Lys Ser Val Thr Asn Glu Asp Val Thr Gln Glu Gln 
        195                 200                 205             


Leu Gly Gly Ala Lys Thr His Thr Thr Val Ser Gly Val Ala His Arg 
    210                 215                 220                 


Ala Phe Asp Asn Asp Val Asp Ala Leu Cys Asn Leu Arg Glu Phe Phe 
225                 230                 235                 240 


Asn Phe Leu Pro Leu Ser Ser Gln Asp Pro Ala Pro Ile Arg Glu Cys 
                245                 250                 255     


His Asp Pro Ser Asp Arg Leu Val Pro Glu Leu Asp Thr Val Val Pro 
            260                 265                 270         


Leu Glu Ser Ser Lys Ala Tyr Asn Met Leu Asp Ile Ile His Ala Val 
        275                 280                 285             


Ile Asp Glu Arg Glu Phe Phe Glu Ile Met Pro Ser Tyr Ala Lys Asn 
    290                 295                 300                 


Ile Val Val Gly Phe Ala Arg Met Asn Gly Arg Thr Val Gly Ile Val 
305                 310                 315                 320 


Gly Asn Gln Pro Asn Val Ala Ser Gly Cys Leu Asp Ile Asn Ser Ser 
                325                 330                 335     


Val Lys Gly Ala Arg Phe Val Arg Phe Cys Asp Ala Phe Asn Ile Pro 
            340                 345                 350         


Leu Ile Thr Phe Val Asp Val Pro Gly Phe Leu Pro Gly Thr Ala Gln 
        355                 360                 365             


Glu Tyr Gly Gly Ile Ile Arg His Gly Ala Lys Leu Leu Tyr Ala Phe 
    370                 375                 380                 


Ala Glu Ala Thr Val Pro Lys Ile Thr Val Ile Thr Arg Lys Ala Tyr 
385                 390                 395                 400 


Gly Gly Ala Tyr Asp Val Met Ser Ser Lys His Leu Leu Gly Asp Thr 
                405                 410                 415     


Asn Tyr Ala Trp Pro Thr Ala Glu Ile Ala Val Met Gly Ala Lys Gly 
            420                 425                 430         


Ala Val Glu Ile Ile Phe Lys Gly His Gln Asp Val Glu Ala Ala Gln 
        435                 440                 445             


Ala Glu Tyr Val Glu Lys Phe Ala Asn Pro Phe Pro Ala Ala Val Arg 
    450                 455                 460                 


Gly Phe Val Asp Asp Ile Ile Gln Pro Ser Ser Thr Arg Ala Arg Ile 
465                 470                 475                 480 


Cys Cys Asp Leu Glu Val Leu Ala Ser Lys Lys Val His Arg Pro Trp 
                485                 490                 495     


Arg Lys His Ala Asn Ile Pro Leu 
            500                 


<210> 9
<211> 20
<212> DNA
<213> Artificial Sequence

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

<400> 9
tgggaaaatg ggcaaggtga                                                   20


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

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

<400> 10
accgaggctc cagcctatta                                                   20


<210> 11
<211> 12
<212> DNA
<213> Artificial Sequence

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

<400> 11
aagatctgca aa                                                           12


<210> 12
<211> 12
<212> DNA
<213> Artificial Sequence

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

<400> 12
tagagcacag ga                                                           12


<210> 13
<211> 14
<212> DNA
<213> Artificial Sequence

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

<400> 13
tattgccaat aacc                                                         14


