﻿               SEQUENCE LISTING

<110> Technische Universität Dresden

<120> Manipulation of hairy and enhancer of split 3 (Hes3) and its regulators/mediators in diabetes, obesity, and metabolic syndrome

<130> X3130 PCT

<150> EP 14 18 5019.8
<151> 2014-09-16

<160> 30

<170> BiSSAP 1.3

<210> 1
<211> 770
<212> PRT
<213> Homo sapiens

<400> 1
Met Ala Gln Trp Asn Gln Leu Gln Gln Leu Asp Thr Arg Tyr Leu Glu 
1               5                   10                  15      
Gln Leu His Gln Leu Tyr Ser Asp Ser Phe Pro Met Glu Leu Arg Gln 
            20                  25                  30          
Phe Leu Ala Pro Trp Ile Glu Ser Gln Asp Trp Ala Tyr Ala Ala Ser 
        35                  40                  45              
Lys Glu Ser His Ala Thr Leu Val Phe His Asn Leu Leu Gly Glu Ile 
    50                  55                  60                  
Asp Gln Gln Tyr Ser Arg Phe Leu Gln Glu Ser Asn Val Leu Tyr Gln 
65                  70                  75                  80  
His Asn Leu Arg Arg Ile Lys Gln Phe Leu Gln Ser Arg Tyr Leu Glu 
                85                  90                  95      
Lys Pro Met Glu Ile Ala Arg Ile Val Ala Arg Cys Leu Trp Glu Glu 
            100                 105                 110         
Ser Arg Leu Leu Gln Thr Ala Ala Thr Ala Ala Gln Gln Gly Gly Gln 
        115                 120                 125             
Ala Asn His Pro Thr Ala Ala Val Val Thr Glu Lys Gln Gln Met Leu 
    130                 135                 140                 
Glu Gln His Leu Gln Asp Val Arg Lys Arg Val Gln Asp Leu Glu Gln 
145                 150                 155                 160 
Lys Met Lys Val Val Glu Asn Leu Gln Asp Asp Phe Asp Phe Asn Tyr 
                165                 170                 175     
Lys Thr Leu Lys Ser Gln Gly Asp Met Gln Asp Leu Asn Gly Asn Asn 
            180                 185                 190         
Gln Ser Val Thr Arg Gln Lys Met Gln Gln Leu Glu Gln Met Leu Thr 
        195                 200                 205             
Ala Leu Asp Gln Met Arg Arg Ser Ile Val Ser Glu Leu Ala Gly Leu 
    210                 215                 220                 
Leu Ser Ala Met Glu Tyr Val Gln Lys Thr Leu Thr Asp Glu Glu Leu 
225                 230                 235                 240 
Ala Asp Trp Lys Arg Arg Gln Gln Ile Ala Cys Ile Gly Gly Pro Pro 
                245                 250                 255     
Asn Ile Cys Leu Asp Arg Leu Glu Asn Trp Ile Thr Ser Leu Ala Glu 
            260                 265                 270         
Ser Gln Leu Gln Thr Arg Gln Gln Ile Lys Lys Leu Glu Glu Leu Gln 
        275                 280                 285             
Gln Lys Val Ser Tyr Lys Gly Asp Pro Ile Val Gln His Arg Pro Met 
    290                 295                 300                 
Leu Glu Glu Arg Ile Val Glu Leu Phe Arg Asn Leu Met Lys Ser Ala 
305                 310                 315                 320 
Phe Val Val Glu Arg Gln Pro Cys Met Pro Met His Pro Asp Arg Pro 
                325                 330                 335     
Leu Val Ile Lys Thr Gly Val Gln Phe Thr Thr Lys Val Arg Leu Leu 
            340                 345                 350         
Val Lys Phe Pro Glu Leu Asn Tyr Gln Leu Lys Ile Lys Val Cys Ile 
        355                 360                 365             
Asp Lys Asp Ser Gly Asp Val Ala Ala Leu Arg Gly Ser Arg Lys Phe 
    370                 375                 380                 
Asn Ile Leu Gly Thr Asn Thr Lys Val Met Asn Met Glu Glu Ser Asn 
385                 390                 395                 400 
Asn Gly Ser Leu Ser Ala Glu Phe Lys His Leu Thr Leu Arg Glu Gln 
                405                 410                 415     
Arg Cys Gly Asn Gly Gly Arg Ala Asn Cys Asp Ala Ser Leu Ile Val 
            420                 425                 430         
Thr Glu Glu Leu His Leu Ile Thr Phe Glu Thr Glu Val Tyr His Gln 
        435                 440                 445             
Gly Leu Lys Ile Asp Leu Glu Thr His Ser Leu Pro Val Val Val Ile 
    450                 455                 460                 
Ser Asn Ile Cys Gln Met Pro Asn Ala Trp Ala Ser Ile Leu Trp Tyr 
465                 470                 475                 480 
Asn Met Leu Thr Asn Asn Pro Lys Asn Val Asn Phe Phe Thr Lys Pro 
                485                 490                 495     
Pro Ile Gly Thr Trp Asp Gln Val Ala Glu Val Leu Ser Trp Gln Phe 
            500                 505                 510         
Ser Ser Thr Thr Lys Arg Gly Leu Ser Ile Glu Gln Leu Thr Thr Leu 
        515                 520                 525             
Ala Glu Lys Leu Leu Gly Pro Gly Val Asn Tyr Ser Gly Cys Gln Ile 
    530                 535                 540                 
Thr Trp Ala Lys Phe Cys Lys Glu Asn Met Ala Gly Lys Gly Phe Ser 
545                 550                 555                 560 
Phe Trp Val Trp Leu Asp Asn Ile Ile Asp Leu Val Lys Lys Tyr Ile 
                565                 570                 575     
Leu Ala Leu Trp Asn Glu Gly Tyr Ile Met Gly Phe Ile Ser Lys Glu 
            580                 585                 590         
Arg Glu Arg Ala Ile Leu Ser Thr Lys Pro Pro Gly Thr Phe Leu Leu 
        595                 600                 605             
Arg Phe Ser Glu Ser Ser Lys Glu Gly Gly Val Thr Phe Thr Trp Val 
    610                 615                 620                 
Glu Lys Asp Ile Ser Gly Lys Thr Gln Ile Gln Ser Val Glu Pro Tyr 
625                 630                 635                 640 
Thr Lys Gln Gln Leu Asn Asn Met Ser Phe Ala Glu Ile Ile Met Gly 
                645                 650                 655     
Tyr Lys Ile Met Asp Ala Thr Asn Ile Leu Val Ser Pro Leu Val Tyr 
            660                 665                 670         
Leu Tyr Pro Asp Ile Pro Lys Glu Glu Ala Phe Gly Lys Tyr Cys Arg 
        675                 680                 685             
Pro Glu Ser Gln Glu His Pro Glu Ala Asp Pro Gly Ser Ala Ala Pro 
    690                 695                 700                 
Tyr Leu Lys Thr Lys Phe Ile Cys Val Thr Pro Thr Thr Cys Ser Asn 
705                 710                 715                 720 
Thr Ile Asp Leu Pro Met Ser Pro Arg Thr Leu Asp Ser Leu Met Gln 
                725                 730                 735     
Phe Gly Asn Asn Gly Glu Gly Ala Glu Pro Ser Ala Gly Gly Gln Phe 
            740                 745                 750         
Glu Ser Leu Thr Phe Asp Met Glu Leu Thr Ser Glu Cys Ala Thr Ser 
        755                 760                 765             
Pro Met 
    770 

<210> 2
<211> 770
<212> PRT
<213> Mus musculus

<400> 2
Met Ala Gln Trp Asn Gln Leu Gln Gln Leu Asp Thr Arg Tyr Leu Glu 
1               5                   10                  15      
Gln Leu His Gln Leu Tyr Ser Asp Ser Phe Pro Met Glu Leu Arg Gln 
            20                  25                  30          
Phe Leu Ala Pro Trp Ile Glu Ser Gln Asp Trp Ala Tyr Ala Ala Ser 
        35                  40                  45              
Lys Glu Ser His Ala Thr Leu Val Phe His Asn Leu Leu Gly Glu Ile 
    50                  55                  60                  
Asp Gln Gln Tyr Ser Arg Phe Leu Gln Glu Ser Asn Val Leu Tyr Gln 
65                  70                  75                  80  
His Asn Leu Arg Arg Ile Lys Gln Phe Leu Gln Ser Arg Tyr Leu Glu 
                85                  90                  95      
Lys Pro Met Glu Ile Ala Arg Ile Val Ala Arg Cys Leu Trp Glu Glu 
            100                 105                 110         
Ser Arg Leu Leu Gln Thr Ala Ala Thr Ala Ala Gln Gln Gly Gly Gln 
        115                 120                 125             
Ala Asn His Pro Thr Ala Ala Val Val Thr Glu Lys Gln Gln Met Leu 
    130                 135                 140                 
Glu Gln His Leu Gln Asp Val Arg Lys Arg Val Gln Asp Leu Glu Gln 
145                 150                 155                 160 
Lys Met Lys Val Val Glu Asn Leu Gln Asp Asp Phe Asp Phe Asn Tyr 
                165                 170                 175     
Lys Thr Leu Lys Ser Gln Gly Asp Met Gln Asp Leu Asn Gly Asn Asn 
            180                 185                 190         
Gln Ser Val Thr Arg Gln Lys Met Gln Gln Leu Glu Gln Met Leu Thr 
        195                 200                 205             
Ala Leu Asp Gln Met Arg Arg Ser Ile Val Ser Glu Leu Ala Gly Leu 
    210                 215                 220                 
Leu Ser Ala Met Glu Tyr Val Gln Lys Thr Leu Thr Asp Glu Glu Leu 
225                 230                 235                 240 
Ala Asp Trp Lys Arg Arg Gln Gln Ile Ala Cys Ile Gly Gly Pro Pro 
                245                 250                 255     
Asn Ile Cys Leu Asp Arg Leu Glu Asn Trp Ile Thr Ser Leu Ala Glu 
            260                 265                 270         
Ser Gln Leu Gln Thr Arg Gln Gln Ile Lys Lys Leu Glu Glu Leu Gln 
        275                 280                 285             
Gln Lys Val Ser Tyr Lys Gly Asp Pro Ile Val Gln His Arg Pro Met 
    290                 295                 300                 
Leu Glu Glu Arg Ile Val Glu Leu Phe Arg Asn Leu Met Lys Ser Ala 
305                 310                 315                 320 
Phe Val Val Glu Arg Gln Pro Cys Met Pro Met His Pro Asp Arg Pro 
                325                 330                 335     
Leu Val Ile Lys Thr Gly Val Gln Phe Thr Thr Lys Val Arg Leu Leu 
            340                 345                 350         
Val Lys Phe Pro Glu Leu Asn Tyr Gln Leu Lys Ile Lys Val Cys Ile 
        355                 360                 365             
Asp Lys Asp Ser Gly Asp Val Ala Ala Leu Arg Gly Ser Arg Lys Phe 
    370                 375                 380                 
Asn Ile Leu Gly Thr Asn Thr Lys Val Met Asn Met Glu Glu Ser Asn 
385                 390                 395                 400 
Asn Gly Ser Leu Ser Ala Glu Phe Lys His Leu Thr Leu Arg Glu Gln 
                405                 410                 415     
Arg Cys Gly Asn Gly Gly Arg Ala Asn Cys Asp Ala Ser Leu Ile Val 
            420                 425                 430         
Thr Glu Glu Leu His Leu Ile Thr Phe Glu Thr Glu Val Tyr His Gln 
        435                 440                 445             
Gly Leu Lys Ile Asp Leu Glu Thr His Ser Leu Pro Val Val Val Ile 
    450                 455                 460                 
Ser Asn Ile Cys Gln Met Pro Asn Ala Trp Ala Ser Ile Leu Trp Tyr 
465                 470                 475                 480 
Asn Met Leu Thr Asn Asn Pro Lys Asn Val Asn Phe Phe Thr Lys Pro 
                485                 490                 495     
Pro Ile Gly Thr Trp Asp Gln Val Ala Glu Val Leu Ser Trp Gln Phe 
            500                 505                 510         
Ser Ser Thr Thr Lys Arg Gly Leu Ser Ile Glu Gln Leu Thr Thr Leu 
        515                 520                 525             
Ala Glu Lys Leu Leu Gly Pro Gly Val Asn Tyr Ser Gly Cys Gln Ile 
    530                 535                 540                 
Thr Trp Ala Lys Phe Cys Lys Glu Asn Met Ala Gly Lys Gly Phe Ser 
545                 550                 555                 560 
Phe Trp Val Trp Leu Asp Asn Ile Ile Asp Leu Val Lys Lys Tyr Ile 
                565                 570                 575     
Leu Ala Leu Trp Asn Glu Gly Tyr Ile Met Gly Phe Ile Ser Lys Glu 
            580                 585                 590         
Arg Glu Arg Ala Ile Leu Ser Thr Lys Pro Pro Gly Thr Phe Leu Leu 
        595                 600                 605             
Arg Phe Ser Glu Ser Ser Lys Glu Gly Gly Val Thr Phe Thr Trp Val 
    610                 615                 620                 
Glu Lys Asp Ile Ser Gly Lys Thr Gln Ile Gln Ser Val Glu Pro Tyr 
625                 630                 635                 640 
Thr Lys Gln Gln Leu Asn Asn Met Ser Phe Ala Glu Ile Ile Met Gly 
                645                 650                 655     
Tyr Lys Ile Met Asp Ala Thr Asn Ile Leu Val Ser Pro Leu Val Tyr 
            660                 665                 670         
Leu Tyr Pro Asp Ile Pro Lys Glu Glu Ala Phe Gly Lys Tyr Cys Arg 
        675                 680                 685             
Pro Glu Ser Gln Glu His Pro Glu Ala Asp Pro Gly Ser Ala Ala Pro 
    690                 695                 700                 
Tyr Leu Lys Thr Lys Phe Ile Cys Val Thr Pro Thr Thr Cys Ser Asn 
705                 710                 715                 720 
Thr Ile Asp Leu Pro Met Ser Pro Arg Thr Leu Asp Ser Leu Met Gln 
                725                 730                 735     
Phe Gly Asn Asn Gly Glu Gly Ala Glu Pro Ser Ala Gly Gly Gln Phe 
            740                 745                 750         
Glu Ser Leu Thr Phe Asp Met Asp Leu Thr Ser Glu Cys Ala Thr Ser 
        755                 760                 765             
Pro Met 
    770 

<210> 3
<211> 770
<212> PRT
<213> Rattus norvegicus

<400> 3
Met Ala Gln Trp Asn Gln Leu Gln Gln Leu Asp Thr Arg Tyr Leu Glu 
1               5                   10                  15      
Gln Leu His Gln Leu Tyr Ser Asp Ser Phe Pro Met Glu Leu Arg Gln 
            20                  25                  30          
Phe Leu Ala Pro Trp Ile Glu Ser Gln Asp Trp Ala Tyr Ala Ala Ser 
        35                  40                  45              
Lys Glu Ser His Ala Thr Leu Val Phe His Asn Leu Leu Gly Glu Ile 
    50                  55                  60                  
Asp Gln Gln Tyr Ser Arg Phe Leu Gln Glu Ser Asn Val Leu Tyr Gln 
65                  70                  75                  80  
His Asn Leu Arg Arg Ile Lys Gln Phe Leu Gln Ser Arg Tyr Leu Glu 
                85                  90                  95      
Lys Pro Met Glu Ile Ala Arg Ile Val Ala Arg Cys Leu Trp Glu Glu 
            100                 105                 110         
Ser Arg Leu Leu Gln Thr Ala Ala Thr Ala Ala Gln Gln Gly Gly Gln 
        115                 120                 125             
Ala Asn His Pro Thr Ala Ala Val Val Thr Glu Lys Gln Gln Met Leu 
    130                 135                 140                 
Glu Gln His Leu Gln Asp Val Arg Lys Arg Val Gln Asp Leu Glu Gln 
145                 150                 155                 160 
Lys Met Lys Val Val Glu Asn Leu Gln Asp Asp Phe Asp Phe Asn Tyr 
                165                 170                 175     
Lys Thr Leu Lys Ser Gln Gly Asp Met Gln Asp Leu Asn Gly Asn Asn 
            180                 185                 190         
Gln Ser Val Thr Arg Gln Lys Met Gln Gln Leu Glu Gln Met Leu Thr 
        195                 200                 205             
Ala Leu Asp Gln Met Arg Arg Ser Ile Val Ser Glu Leu Ala Gly Leu 
    210                 215                 220                 
Leu Ser Ala Met Glu Tyr Val Gln Lys Thr Leu Thr Asp Glu Glu Leu 
225                 230                 235                 240 
Ala Asp Trp Lys Arg Arg Gln Gln Ile Ala Cys Ile Gly Gly Pro Pro 
                245                 250                 255     
Asn Ile Cys Leu Asp Arg Leu Glu Asn Trp Ile Thr Ser Leu Ala Glu 
            260                 265                 270         
Ser Gln Leu Gln Thr Arg Gln Gln Ile Lys Lys Leu Glu Glu Leu Gln 
        275                 280                 285             
Gln Lys Val Ser Tyr Lys Gly Asp Pro Ile Val Gln His Arg Pro Met 
    290                 295                 300                 
Leu Glu Glu Arg Ile Val Asp Leu Phe Arg Asn Leu Met Lys Ser Ala 
305                 310                 315                 320 
Phe Val Val Glu Arg Gln Pro Cys Met Pro Met His Pro Asp Arg Pro 
                325                 330                 335     
Leu Val Ile Lys Thr Gly Val Gln Phe Thr Thr Lys Val Arg Leu Leu 
            340                 345                 350         
Val Lys Phe Pro Glu Leu Asn Tyr Gln Leu Lys Ile Lys Val Cys Ile 
        355                 360                 365             
Asp Lys Asp Ser Gly Asp Val Ala Ala Leu Arg Gly Ser Arg Lys Phe 
    370                 375                 380                 
Asn Ile Leu Gly Thr Asn Thr Lys Val Met Asn Met Glu Glu Ser Asn 
385                 390                 395                 400 
Asn Gly Ser Leu Ser Ala Glu Phe Lys His Leu Thr Leu Arg Glu Gln 
                405                 410                 415     
Arg Cys Gly Asn Gly Gly Arg Ala Asn Cys Asp Ala Ser Leu Ile Val 
            420                 425                 430         
Thr Glu Glu Leu His Leu Ile Thr Phe Glu Thr Glu Val Tyr His Gln 
        435                 440                 445             
Gly Leu Lys Ile Asp Leu Glu Thr His Ser Leu Pro Val Val Val Ile 
    450                 455                 460                 
Ser Asn Ile Cys Gln Met Pro Asn Ala Trp Ala Ser Ile Leu Trp Tyr 
465                 470                 475                 480 
Asn Met Leu Thr Asn Asn Pro Lys Asn Val Asn Phe Phe Thr Lys Pro 
                485                 490                 495     
Pro Ile Gly Thr Trp Asp Gln Val Ala Glu Val Leu Ser Trp Gln Phe 
            500                 505                 510         
Ser Ser Thr Thr Lys Arg Gly Leu Ser Ile Glu Gln Leu Thr Thr Leu 
        515                 520                 525             
Ala Glu Lys Leu Leu Gly Pro Gly Val Asn Tyr Ser Gly Cys Gln Ile 
    530                 535                 540                 
Thr Trp Ala Lys Phe Cys Lys Glu Asn Met Ala Gly Lys Gly Phe Ser 
545                 550                 555                 560 
Phe Trp Val Trp Leu Asp Asn Ile Ile Asp Leu Val Lys Lys Tyr Ile 
                565                 570                 575     
Leu Ala Leu Trp Asn Glu Gly Tyr Ile Met Gly Phe Ile Ser Lys Glu 
            580                 585                 590         
Arg Glu Arg Ala Ile Leu Ser Thr Lys Pro Pro Gly Thr Phe Leu Leu 
        595                 600                 605             
Arg Phe Ser Glu Ser Ser Lys Glu Gly Gly Val Thr Phe Thr Trp Val 
    610                 615                 620                 
Glu Lys Asp Ile Ser Gly Lys Thr Gln Ile Gln Ser Val Glu Pro Tyr 
625                 630                 635                 640 
Thr Lys Gln Gln Leu Asn Asn Met Ser Phe Ala Glu Ile Ile Met Gly 
                645                 650                 655     
Tyr Lys Ile Met Asp Ala Thr Asn Ile Leu Val Ser Pro Leu Val Tyr 
            660                 665                 670         
Leu Tyr Pro Asp Ile Pro Lys Glu Glu Ala Phe Gly Lys Tyr Cys Arg 
        675                 680                 685             
Pro Glu Ser Gln Glu His Pro Glu Ala Asp Pro Gly Ser Ala Ala Pro 
    690                 695                 700                 
Tyr Leu Lys Thr Lys Phe Ile Cys Val Thr Pro Thr Thr Cys Ser Asn 
705                 710                 715                 720 
Thr Ile Asp Leu Pro Met Ser Pro Arg Thr Leu Asp Ser Leu Met Gln 
                725                 730                 735     
Phe Gly Asn Asn Gly Glu Gly Ala Glu Pro Ser Ala Gly Gly Gln Phe 
            740                 745                 750         
Glu Ser Leu Thr Phe Asp Met Asp Leu Thr Ser Glu Cys Ala Thr Ser 
        755                 760                 765             
Pro Met 
    770 

<210> 4
<211> 186
<212> PRT
<213> Homo sapiens

<400> 4
Met Glu Lys Lys Arg Arg Ala Arg Ile Asn Val Ser Leu Glu Gln Leu 
1               5                   10                  15      
Lys Ser Leu Leu Glu Lys His Tyr Ser His Gln Ile Arg Lys Arg Lys 
            20                  25                  30          
Leu Glu Lys Ala Asp Ile Leu Glu Leu Ser Val Lys Tyr Met Arg Ser 
        35                  40                  45              
Leu Gln Asn Ser Leu Gln Gly Leu Trp Pro Val Pro Arg Gly Ala Glu 
    50                  55                  60                  
Gln Pro Ser Gly Phe Arg Ser Cys Leu Pro Gly Val Ser Gln Leu Leu 
65                  70                  75                  80  
Arg Arg Gly Asp Glu Val Gly Ser Gly Leu Arg Cys Pro Leu Val Pro 
                85                  90                  95      
Glu Ser Ala Ala Gly Ser Thr Met Asp Ser Ala Gly Leu Gly Gln Glu 
            100                 105                 110         
Ala Pro Ala Leu Phe Arg Pro Cys Thr Pro Ala Val Trp Ala Pro Ala 
        115                 120                 125             
Pro Ala Ala Gly Gly Pro Arg Ser Pro Pro Pro Leu Leu Leu Leu Pro 
    130                 135                 140                 
Glu Ser Leu Pro Gly Ser Ser Ala Ser Val Pro Pro Pro Gln Pro Ala 
145                 150                 155                 160 
Ser Ser Arg Cys Ala Glu Ser Pro Gly Leu Gly Leu Arg Val Trp Arg 
                165                 170                 175     
Pro Trp Gly Ser Pro Gly Asp Asp Leu Asn 
            180                 185     

<210> 5
<211> 175
<212> PRT
<213> Mus musculus

<400> 5
Met Glu Lys Lys Arg Arg Ala Arg Ile Asn Val Ser Leu Glu Gln Leu 
1               5                   10                  15      
Arg Ser Leu Leu Glu Arg His Tyr Ser His Gln Ile Arg Lys Arg Lys 
            20                  25                  30          
Leu Glu Lys Ala Asp Ile Leu Glu Leu Ser Val Lys Tyr Met Arg Ser 
        35                  40                  45              
Leu Gln Asn Ser Leu Gln Gly Leu Trp Pro Val Pro Ser Gly Val Asp 
    50                  55                  60                  
Tyr Pro Ser Gly Phe Gln Gly Gly Leu Arg Gly Val Ser Gln Arg Leu 
65                  70                  75                  80  
Arg Pro Gly Glu Gly Asp Ser Gly Leu Arg Cys Pro Leu Leu Leu Gln 
                85                  90                  95      
Arg Arg Glu Gly Ser Thr Thr Asp Ser Ala Asn Pro Gln Ala Thr Ser 
            100                 105                 110         
Val Leu Asn Pro Cys Leu Pro Ala Ile Trp Ala Pro Ser Arg Ala Ala 
        115                 120                 125             
Gly Gly Ser His Ser Pro Gln Ser Pro Leu Pro Leu Pro Gly Gly Leu 
    130                 135                 140                 
Leu Glu Ser Ser Thr Asp Val Val Ala Pro His Pro Ala Ser Asn Cys 
145                 150                 155                 160 
Gln Ala Glu Ser Thr Arg Pro Gly Phe Arg Val Trp Arg Pro Trp 
                165                 170                 175 

<210> 6
<211> 200
<212> PRT
<213> Mus musculus

<400> 6
Met Gly Thr Glu Pro Thr Ser Arg Asp Ser Leu Gly Gly Pro Ala Ser 
1               5                   10                  15      
Ser Phe Arg Lys Ile Ser Lys Pro Leu Met Glu Lys Lys Arg Arg Ala 
            20                  25                  30          
Arg Ile Asn Val Ser Leu Glu Gln Leu Arg Ser Leu Leu Glu Arg His 
        35                  40                  45              
Tyr Ser His Gln Ile Arg Lys Arg Lys Leu Glu Lys Ala Asp Ile Leu 
    50                  55                  60                  
Glu Leu Ser Val Lys Tyr Met Arg Ser Leu Gln Asn Ser Leu Gln Gly 
65                  70                  75                  80  
Leu Trp Pro Val Pro Ser Gly Val Asp Tyr Pro Ser Gly Phe His Gly 
                85                  90                  95      
Gly Leu Arg Gly Val Ser Gln Arg Leu Arg Pro Gly Glu Gly Asp Ser 
            100                 105                 110         
Gly Leu Arg Cys Pro Leu Leu Leu Gln Arg Arg Glu Gly Ser Thr Thr 
        115                 120                 125             
Asp Ser Ala Asn Pro Gln Ala Thr Ser Val Leu Asn Pro Cys Leu Pro 
    130                 135                 140                 
Ala Ile Trp Ala Pro Ser Arg Ala Ala Gly Gly Ser His Ser Pro Gln 
145                 150                 155                 160 
Ser Pro Leu Pro Leu Pro Gly Gly Leu Leu Glu Ser Ser Thr Asp Val 
                165                 170                 175     
Val Ala Pro Gln Pro Ala Ser Asn Cys Gln Ala Glu Ser Thr Arg Pro 
            180                 185                 190         
Gly Phe Arg Val Trp Arg Pro Trp 
        195                 200 

<210> 7
<211> 175
<212> PRT
<213> Rattus norvegicus

<400> 7
Met Glu Lys Lys Arg Arg Ala Arg Ile Asn Leu Ser Leu Glu Gln Leu 
1               5                   10                  15      
Arg Ser Leu Leu Glu Arg His Tyr Ser His Gln Ile Arg Lys Arg Lys 
            20                  25                  30          
Leu Glu Lys Ala Asp Ile Leu Glu Leu Ser Val Lys Tyr Val Arg Ser 
        35                  40                  45              
Leu Gln Asn Ser Leu Gln Gly Leu Trp Leu Val Pro Ser Gly Val Asp 
    50                  55                  60                  
Tyr Pro Ser Gly Phe Arg Gly Gly Leu Pro Gly Ser Ser Gln Arg Leu 
65                  70                  75                  80  
Arg Pro Gly Glu Asp Asp Ser Gly Leu Arg Cys Pro Leu Leu Leu Gln 
                85                  90                  95      
Arg Arg Ala Gly Ser Thr Thr Asp Ser Ala Asn Pro Gln Thr Ala Ser 
            100                 105                 110         
Val Leu Ser Pro Cys Leu Pro Ala Ile Trp Ala Pro Gly Pro Pro Ala 
        115                 120                 125             
Gly Gly Ser Gln Ser Pro Gln Ser Pro Phe Pro Pro Leu Gly Gly Leu 
    130                 135                 140                 
Leu Glu Ser Ser Thr Gly Ile Leu Ala Pro Pro Pro Ala Ser Asn Cys 
145                 150                 155                 160 
Gln Ala Glu Asn Pro Arg Pro Gly Phe Arg Val Trp Arg Pro Trp 
                165                 170                 175 

<210> 8
<211> 697
<212> DNA
<213> Homo sapiens

<400> 8
tgggcacgga gcctgctgcc cggggcagcc tccccggcaa cttccgaaag atttccaagc      60

cgctgatgga gaaaaagcgc cgggcacgca tcaatgtgtc actggagcag ctcaagtcgc     120

tgctggagaa acactactcg caccagatcc ggaagcgcaa attggagaag gccgacatcc     180

tggagttgag cgtgaagtac atgagaagcc ttcagaactc cttgcaaggg ctctggcctg     240

tgcccagggg agccgagcaa ccgtcgggct tccgcagctg cctgcccggc gtgagccagc     300

tccttcggcg cggagatgag gtcggcagcg gcctgcgctg ccccctggtg cccgagagcg     360

ccgccggcag caccatggac agcgccgggt tgggccagga ggcgcccgcg ctgttccgcc     420

cttgcacccc tgccgtctgg gctcctgctc cggccgccgg cggcccgcgg tccccaccac     480

ccctgctcct cctccccgaa agtctccctg gctcgtccgc cagcgtcccc ccgccgcagc     540

cagcgtcgag tcgctgcgcc gagagtcccg ggctgggcct gcgcgtgtgg cggccctggg     600

gaagccccgg ggatgacctg aactgaaggc gctccctatt tggtctcgcg acacagggac     660

tattttcagc acgcccacag tgactgccag gaccccc                              697


<210> 9
<211> 1829
<212> DNA
<213> Mus musculus

<400> 9
gctcagagag gacaaagtga gcagctgtct ctccttaccg ctgggaaagc tctcttctgg      60

gtgggtctgc ctgtggacgc aggccctgct tgcgactggc tttgagcaac cacaggcaga     120

aaattgctac attgtcctga cattagggcg actaattcag catcccagcg tggccagagc     180

gtgaagggag cagaaaagca tcactggcca gcatccttgc ctcagcatct ttatcaggcc     240

tcaggacacc cagagctcca ccatcatcat ttaggacggc ccccagctct caaagctccc     300

tgccatagcg gaggaccacc agaagaatgc tggctaagaa gcagccagga cttggcaagc     360

agacatagtg atctccaagc ctctgatgga gaagaagcgc cgtgcacgca tcaacgtgtc     420

actggagcag ctgaggtctc ttctggagag acactactca catcagatac ggaaacgaaa     480

gctggagaag gccgatatcc tggagctgag tgttaagtac atgagaagcc tccagaactc     540

actgcaagga ctctggccag tacccagtgg ggtggactac ccgtccggct tccaaggcgg     600

cttgcgtggc gtgagccaga ggcttcggcc cggagaggga gacagcggcc tgcgctgccc     660

cttgctgctc cagcgcaggg aaggcagcac cacggacagc gccaacccac aggcgacctc     720

tgttctcaac ccttgcctcc cggccatctg ggcccccagt cgcgctgcag gtggctccca     780

ctccccgcag tccccgctcc ctctccctgg aggtctcctt gagtcttcca ccgatgttgt     840

ggcaccacat cctgcatcaa actgccaggc cgagagtacg agacccgggt ttcgcgtgtg     900

gcgaccgtgg tgagacgtag gcaaggattt agactcaagc tctctcccca cgtccccatc     960

accccgccat ctagtctggg gaaactattt tggggcaccc atggtgactg caggaactct    1020

atcaatcggt ggcctggggg gggggagtgc aggaaatcca cggaaccatt ggcgattcgg    1080

gtctgcactg ctaggtgaac tcatccactc cagccccacc cactccatcc agaccagctc    1140

tctacctccc gcttctagag aagatgggag gggacgggtg agctgtaccc ctttcccagg    1200

gacccggggc tggcagcccg cccctgcccc ctctccacgg ctgcgtcacg gtgagaaggt    1260

cgcggttgct tgcagcacag agcggacccc tcgcagcgag gagaatcgct gccccgccct    1320

ggcccattca accggcctcg cgcgctccgt tcccaccggc acaaagcggg ccgggctccg    1380

ccccttcagc aaggggctcc catcctatca ccacccaaga ccttctcact accatcgaaa    1440

cccatcaccc cctctacacc gattccacac tgctggggcg ctctcaggcc ctcaactgcg    1500

caaatactta tggctgcggc gtgctggcgt agaacattgg atccgcccct aaggtacttg    1560

cgtgcccgac gccccgccta gccacaatct atagtcctgg gtcccaccca tccctgctta    1620

gcactgctga gacctgagca ttttgtgttc tgcaaagacc actttagtgc cttctgagcc    1680

ctggactcga actaagagcc tgttagttac catgagcgtc gactgtgttg gggagagggc    1740

tcctgtcgtg gaccagtctg gggtccagtg caaaatccca gaatctctta ttaccaatat    1800

acaattatga ataaagactg ggcgtgaat                                      1829


<210> 10
<211> 964
<212> DNA
<213> Rattus norvegicus

<400> 10
gtggatgcag gccctgcttg caactggctt tgagcaacca caggcagaaa attgctacat      60

tgtcctgaca ttagggcgac taattcagca tcccagcgtg gccagagcgt gaagggagca     120

gaaaagcatc actggccagc atcctcgcct cagcatcttt atcaggcctc aggacaccta     180

gcgccccacc atcatcattt aggatggacc ccagctcaca cagctccctg ccataacgga     240

ggaccaccag aagaatgttg gatctccaag cctctgatgg agaagaagcg tcgtgcccgc     300

atcaacctgt cactggagca gctaaggtct cttctggaga gacactactc ccaccagata     360

cggaagcgaa agctggagaa ggccgatatc ctggagctga gcgttaagta cgtgagaagc     420

ctccagaact cattgcaagg actttggcta gtacccagtg gggtggacta cccgtccgga     480

ttccgaggcg gcttgccggg ctccagccag aggcttcggc ccggagagga cgacagcggc     540

ctgcgctgcc ccctgcttct ccagcgcagg gcaggcagca ccacggacag cgccaaccca     600

cagacggcct ctgttctcag cccctgcctc ccggccatct gggcccctgg tccccctgca     660

ggtggctccc aatccccgca gtccccgttc cctccccttg gaggtctcct tgagtcctcc     720

actggcattc tggcaccgcc acctgcatca aactgccagg ccgagaatcc gagacccggg     780

tttcgcgtgt ggcggccctg gtgaggccta ggcaagaatt tagattcaag ccctaacctc     840

tgcccttatc acctcgccgt ctagtttggg ggaaactatt tggggacacc catggtgact     900

gcagggactc tatcaatcgg tggcctggtg gggctgcagg gaaatacacg gagccatttg     960

ctga                                                                  964


<210> 11
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse HES3a forward primer

<400> 11
aagctccctg ccatagcgga                                                20


<210> 12
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse HES3a reverse primer

<400> 12
atgcgtgcac ggcgcttctt                                                20


<210> 13
<211> 30
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse HES3b forward primer

<400> 13
acatcacagc atgggcaccg agcccacatc                                     30


<210> 14
<211> 25
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse HES3b reverse primer

<400> 14
gttgatgcgt gcacggcgct tcttc                                          25


<210> 15
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse HES3 forward primer

<400> 15
atctccaagc ctctgatgga gaa                                            23


<210> 16
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse HES3 reverse primer

<400> 16
agctttcgtt tccgtatctg atg                                            23


<210> 17
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human Hes3 forward primer

<400> 17
gagaagcctt cagaactcct tgc                                            23


<210> 18
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human Hes3 reverse primer

<400> 18
ctgccgacct catctccgcg                                                20


<210> 19
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse Pdx1 forward primer

<400> 19
ccaccccagt ttacaagctc                                                20


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

<220> 
<223> Mouse Pdx1 reverse primer

<400> 20
tgtaggcagt acgggtcctc                                                20


<210> 21
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human Pdx1 forward primer

<400> 21
ctttctcctc ctcctccttc ta                                             22


<210> 22
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human Pdx1 reverse primer

<400> 22
ggtcatactg gctcgtgaat ag                                             22


<210> 23
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse Insulin forward primer

<400> 23
gaccagctat aatcagagac c                                              21


<210> 24
<211> 22
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse Insulin reverse primer

<400> 24
agttgcagta gttctccagc tg                                             22


<210> 25
<211> 18
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human Insulin forward primer

<400> 25
atcactgtcc ttctgcca                                                  18


<210> 26
<211> 18
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human Insulin reverse primer

<400> 26
gggtgtgtag aagaagcc                                                  18


<210> 27
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse GAPDH forward primer

<400> 27
ctggagaaac ctgccaagta                                                20


<210> 28
<211> 20
<212> DNA
<213> Artificial Sequence

<220> 
<223> Mouse GAPDH reverse primer

<400> 28
tgttgctgta gccgtattca                                                20


<210> 29
<211> 21
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human beta actin forward primer

<400> 29
gccgtcttgc cctccatcgt g                                              21


<210> 30
<211> 23
<212> DNA
<213> Artificial Sequence

<220> 
<223> Human beta actin reverse primer

<400> 30
ggagccacac gcagctcatt gta                                            23


