                         SEQUENCE LISTING

<110>  The John Hopkins University
 
<120>  Engineered TSC2

<130>  44807-0145WO1

<150>  US 62/532,909
<151>  2017-07-14

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  1807
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human TSC2 polypeptide having a S1364A substitution

<400>  1

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


Ile Leu Leu Gly Leu Gly Thr Pro Arg Pro Asn Pro Arg Ser Ala Glu 
            20                  25                  30          


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ala Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Met Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Glu Val Ala Lys Thr Lys Lys Phe Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


Leu Trp Lys Ala Val Ala Asp Leu Leu Gln Pro Glu Arg Pro Leu Glu 
                85                  90                  95      


Ala Arg His Ala Val Leu Ala Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Glu Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Asp Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Arg Met Val Gln Met Ile Cys Leu Leu Cys Val Arg 
        195                 200                 205             


Thr Ala Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Val Thr Leu Cys Arg Thr Ile Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys His Leu Met Glu Asp Arg Ala Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Gln Ala Met Ala Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Val Val Ala Trp Asp Ile Leu Leu Asn Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Thr Leu Asp Ser Pro Glu Leu Arg Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Phe Glu Leu Val Glu Arg Cys Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Ser Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Ala Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Ser Glu Ser Arg Gly Ala Val Arg Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Asn Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Pro Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Val Ala Ala Tyr Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Met Leu Val Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Ser Tyr Thr Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Val Cys Asp Tyr Met Glu Pro Glu Arg Gly Ser Glu 
                645                 650                 655     


Lys Lys Thr Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Gly Pro 
            660                 665                 670         


Ala Pro Ala Gly Pro Ala Val Arg Leu Gly Ser Val Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Ser Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Gly Arg Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Cys Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Gly Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Ala Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Lys 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile His Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ser Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Val Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Ala Ala Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Phe Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Ser Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Pro Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Ser Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Val 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Ser Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Glu Leu Gln Ser  Gly Pro Glu Ser Ser  Ser Ser Pro 
    1085                 1090                 1095             


Gly Val  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Ala Leu Asp 
    1130                 1135                 1140             


Val Pro  Ala Ser Gln Phe Leu  Gly Ser Ala Thr Ser  Pro Gly Pro 
    1145                 1150                 1155             


Arg Thr  Ala Pro Ala Ala Lys  Pro Glu Lys Ala Ser  Ala Gly Thr 
    1160                 1165                 1170             


Arg Val  Pro Val Gln Glu Lys  Thr Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Arg  Asp Thr Ala 
    1235                 1240                 1245             


Leu Tyr  Lys Ser Leu Ser Val  Pro Ala Ala Ser Thr  Ala Lys Pro 
    1250                 1255                 1260             


Pro Pro  Leu Pro Arg Ser Asn  Thr Val Ala Ser Phe  Ser Ser Leu 
    1265                 1270                 1275             


Tyr Gln  Ser Ser Cys Gln Gly  Gln Leu His Arg Ser  Val Ser Trp 
    1280                 1285                 1290             


Ala Asp  Ser Ala Val Val Met  Glu Glu Gly Ser Pro  Gly Glu Val 
    1295                 1300                 1305             


Pro Val  Leu Val Glu Pro Pro  Gly Leu Glu Asp Val  Glu Ala Ala 
    1310                 1315                 1320             


Leu Gly  Met Asp Arg Arg Thr  Asp Ala Tyr Ser Arg  Ser Ser Ser 
    1325                 1330                 1335             


Val Ser  Ser Gln Glu Glu Lys  Ser Leu His Ala Glu  Glu Leu Val 
    1340                 1345                 1350             


Gly Arg  Gly Ile Pro Ile Glu  Arg Val Val Ala Ser  Glu Gly Gly 
    1355                 1360                 1365             


Arg Pro  Ser Val Asp Leu Ser  Phe Gln Pro Ser Gln  Pro Leu Ser 
    1370                 1375                 1380             


Lys Ser  Ser Ser Ser Pro Glu  Leu Gln Thr Leu Gln  Asp Ile Leu 
    1385                 1390                 1395             


Gly Asp  Pro Gly Asp Lys Ala  Asp Val Gly Arg Leu  Ser Pro Glu 
    1400                 1405                 1410             


Val Lys  Ala Arg Ser Gln Ser  Gly Thr Leu Asp Gly  Glu Ser Ala 
    1415                 1420                 1425             


Ala Trp  Ser Ala Ser Gly Glu  Asp Ser Arg Gly Gln  Pro Glu Gly 
    1430                 1435                 1440             


Pro Leu  Pro Ser Ser Ser Pro  Arg Ser Pro Ser Gly  Leu Arg Pro 
    1445                 1450                 1455             


Arg Gly  Tyr Thr Ile Ser Asp  Ser Ala Pro Ser Arg  Arg Gly Lys 
    1460                 1465                 1470             


Arg Val  Glu Arg Asp Ala Leu  Lys Ser Arg Ala Thr  Ala Ser Asn 
    1475                 1480                 1485             


Ala Glu  Lys Val Pro Gly Ile  Asn Pro Ser Phe Val  Phe Leu Gln 
    1490                 1495                 1500             


Leu Tyr  His Ser Pro Phe Phe  Gly Asp Glu Ser Asn  Lys Pro Ile 
    1505                 1510                 1515             


Leu Leu  Pro Asn Glu Ser Gln  Ser Phe Glu Arg Ser  Val Gln Leu 
    1520                 1525                 1530             


Leu Asp  Gln Ile Pro Ser Tyr  Asp Thr His Lys Ile  Ala Val Leu 
    1535                 1540                 1545             


Tyr Val  Gly Glu Gly Gln Ser  Asn Ser Glu Leu Ala  Ile Leu Ser 
    1550                 1555                 1560             


Asn Glu  His Gly Ser Tyr Arg  Tyr Thr Glu Phe Leu  Thr Gly Leu 
    1565                 1570                 1575             


Gly Arg  Leu Ile Glu Leu Lys  Asp Cys Gln Pro Asp  Lys Val Tyr 
    1580                 1585                 1590             


Leu Gly  Gly Leu Asp Val Cys  Gly Glu Asp Gly Gln  Phe Thr Tyr 
    1595                 1600                 1605             


Cys Trp  His Asp Asp Ile Met  Gln Ala Val Phe His  Ile Ala Thr 
    1610                 1615                 1620             


Leu Met  Pro Thr Lys Asp Val  Asp Lys His Arg Cys  Asp Lys Lys 
    1625                 1630                 1635             


Arg His  Leu Gly Asn Asp Phe  Val Ser Ile Val Tyr  Asn Asp Ser 
    1640                 1645                 1650             


Gly Glu  Asp Phe Lys Leu Gly  Thr Ile Lys Gly Gln  Phe Asn Phe 
    1655                 1660                 1665             


Val His  Val Ile Val Thr Pro  Leu Asp Tyr Glu Cys  Asn Leu Val 
    1670                 1675                 1680             


Ser Leu  Gln Cys Arg Lys Asp  Met Glu Gly Leu Val  Asp Thr Ser 
    1685                 1690                 1695             


Val Ala  Lys Ile Val Ser Asp  Arg Asn Leu Pro Phe  Val Ala Arg 
    1700                 1705                 1710             


Gln Met  Ala Leu His Ala Asn  Met Ala Ser Gln Val  His His Ser 
    1715                 1720                 1725             


Arg Ser  Asn Pro Thr Asp Ile  Tyr Pro Ser Lys Trp  Ile Ala Arg 
    1730                 1735                 1740             


Leu Arg  His Ile Lys Arg Leu  Arg Gln Arg Ile Cys  Glu Glu Ala 
    1745                 1750                 1755             


Ala Tyr  Ser Asn Pro Ser Leu  Pro Leu Val His Pro  Pro Ser His 
    1760                 1765                 1770             


Ser Lys  Ala Pro Ala Gln Thr  Pro Ala Glu Pro Thr  Pro Gly Tyr 
    1775                 1780                 1785             


Glu Val  Gly Gln Arg Lys Arg  Leu Ile Ser Ser Val  Glu Asp Phe 
    1790                 1795                 1800             


Thr Glu  Phe Val 
    1805         


<210>  2
<211>  1807
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  human TSC2 polypeptide having a S1364E substitution

<400>  2

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


Ile Leu Leu Gly Leu Gly Thr Pro Arg Pro Asn Pro Arg Ser Ala Glu 
            20                  25                  30          


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ala Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Met Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Glu Val Ala Lys Thr Lys Lys Phe Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


Leu Trp Lys Ala Val Ala Asp Leu Leu Gln Pro Glu Arg Pro Leu Glu 
                85                  90                  95      


Ala Arg His Ala Val Leu Ala Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Glu Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Asp Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Arg Met Val Gln Met Ile Cys Leu Leu Cys Val Arg 
        195                 200                 205             


Thr Ala Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Val Thr Leu Cys Arg Thr Ile Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys His Leu Met Glu Asp Arg Ala Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Gln Ala Met Ala Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Val Val Ala Trp Asp Ile Leu Leu Asn Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Thr Leu Asp Ser Pro Glu Leu Arg Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Phe Glu Leu Val Glu Arg Cys Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Ser Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Ala Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Ser Glu Ser Arg Gly Ala Val Arg Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Asn Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Pro Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Val Ala Ala Tyr Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Met Leu Val Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Ser Tyr Thr Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Val Cys Asp Tyr Met Glu Pro Glu Arg Gly Ser Glu 
                645                 650                 655     


Lys Lys Thr Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Gly Pro 
            660                 665                 670         


Ala Pro Ala Gly Pro Ala Val Arg Leu Gly Ser Val Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Ser Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Gly Arg Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Cys Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Gly Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Ala Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Lys 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile His Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ser Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Val Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Ala Ala Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Phe Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Ser Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Pro Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Ser Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Val 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Ser Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Glu Leu Gln Ser  Gly Pro Glu Ser Ser  Ser Ser Pro 
    1085                 1090                 1095             


Gly Val  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Ala Leu Asp 
    1130                 1135                 1140             


Val Pro  Ala Ser Gln Phe Leu  Gly Ser Ala Thr Ser  Pro Gly Pro 
    1145                 1150                 1155             


Arg Thr  Ala Pro Ala Ala Lys  Pro Glu Lys Ala Ser  Ala Gly Thr 
    1160                 1165                 1170             


Arg Val  Pro Val Gln Glu Lys  Thr Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Arg  Asp Thr Ala 
    1235                 1240                 1245             


Leu Tyr  Lys Ser Leu Ser Val  Pro Ala Ala Ser Thr  Ala Lys Pro 
    1250                 1255                 1260             


Pro Pro  Leu Pro Arg Ser Asn  Thr Val Ala Ser Phe  Ser Ser Leu 
    1265                 1270                 1275             


Tyr Gln  Ser Ser Cys Gln Gly  Gln Leu His Arg Ser  Val Ser Trp 
    1280                 1285                 1290             


Ala Asp  Ser Ala Val Val Met  Glu Glu Gly Ser Pro  Gly Glu Val 
    1295                 1300                 1305             


Pro Val  Leu Val Glu Pro Pro  Gly Leu Glu Asp Val  Glu Ala Ala 
    1310                 1315                 1320             


Leu Gly  Met Asp Arg Arg Thr  Asp Ala Tyr Ser Arg  Ser Ser Ser 
    1325                 1330                 1335             


Val Ser  Ser Gln Glu Glu Lys  Ser Leu His Ala Glu  Glu Leu Val 
    1340                 1345                 1350             


Gly Arg  Gly Ile Pro Ile Glu  Arg Val Val Glu Ser  Glu Gly Gly 
    1355                 1360                 1365             


Arg Pro  Ser Val Asp Leu Ser  Phe Gln Pro Ser Gln  Pro Leu Ser 
    1370                 1375                 1380             


Lys Ser  Ser Ser Ser Pro Glu  Leu Gln Thr Leu Gln  Asp Ile Leu 
    1385                 1390                 1395             


Gly Asp  Pro Gly Asp Lys Ala  Asp Val Gly Arg Leu  Ser Pro Glu 
    1400                 1405                 1410             


Val Lys  Ala Arg Ser Gln Ser  Gly Thr Leu Asp Gly  Glu Ser Ala 
    1415                 1420                 1425             


Ala Trp  Ser Ala Ser Gly Glu  Asp Ser Arg Gly Gln  Pro Glu Gly 
    1430                 1435                 1440             


Pro Leu  Pro Ser Ser Ser Pro  Arg Ser Pro Ser Gly  Leu Arg Pro 
    1445                 1450                 1455             


Arg Gly  Tyr Thr Ile Ser Asp  Ser Ala Pro Ser Arg  Arg Gly Lys 
    1460                 1465                 1470             


Arg Val  Glu Arg Asp Ala Leu  Lys Ser Arg Ala Thr  Ala Ser Asn 
    1475                 1480                 1485             


Ala Glu  Lys Val Pro Gly Ile  Asn Pro Ser Phe Val  Phe Leu Gln 
    1490                 1495                 1500             


Leu Tyr  His Ser Pro Phe Phe  Gly Asp Glu Ser Asn  Lys Pro Ile 
    1505                 1510                 1515             


Leu Leu  Pro Asn Glu Ser Gln  Ser Phe Glu Arg Ser  Val Gln Leu 
    1520                 1525                 1530             


Leu Asp  Gln Ile Pro Ser Tyr  Asp Thr His Lys Ile  Ala Val Leu 
    1535                 1540                 1545             


Tyr Val  Gly Glu Gly Gln Ser  Asn Ser Glu Leu Ala  Ile Leu Ser 
    1550                 1555                 1560             


Asn Glu  His Gly Ser Tyr Arg  Tyr Thr Glu Phe Leu  Thr Gly Leu 
    1565                 1570                 1575             


Gly Arg  Leu Ile Glu Leu Lys  Asp Cys Gln Pro Asp  Lys Val Tyr 
    1580                 1585                 1590             


Leu Gly  Gly Leu Asp Val Cys  Gly Glu Asp Gly Gln  Phe Thr Tyr 
    1595                 1600                 1605             


Cys Trp  His Asp Asp Ile Met  Gln Ala Val Phe His  Ile Ala Thr 
    1610                 1615                 1620             


Leu Met  Pro Thr Lys Asp Val  Asp Lys His Arg Cys  Asp Lys Lys 
    1625                 1630                 1635             


Arg His  Leu Gly Asn Asp Phe  Val Ser Ile Val Tyr  Asn Asp Ser 
    1640                 1645                 1650             


Gly Glu  Asp Phe Lys Leu Gly  Thr Ile Lys Gly Gln  Phe Asn Phe 
    1655                 1660                 1665             


Val His  Val Ile Val Thr Pro  Leu Asp Tyr Glu Cys  Asn Leu Val 
    1670                 1675                 1680             


Ser Leu  Gln Cys Arg Lys Asp  Met Glu Gly Leu Val  Asp Thr Ser 
    1685                 1690                 1695             


Val Ala  Lys Ile Val Ser Asp  Arg Asn Leu Pro Phe  Val Ala Arg 
    1700                 1705                 1710             


Gln Met  Ala Leu His Ala Asn  Met Ala Ser Gln Val  His His Ser 
    1715                 1720                 1725             


Arg Ser  Asn Pro Thr Asp Ile  Tyr Pro Ser Lys Trp  Ile Ala Arg 
    1730                 1735                 1740             


Leu Arg  His Ile Lys Arg Leu  Arg Gln Arg Ile Cys  Glu Glu Ala 
    1745                 1750                 1755             


Ala Tyr  Ser Asn Pro Ser Leu  Pro Leu Val His Pro  Pro Ser His 
    1760                 1765                 1770             


Ser Lys  Ala Pro Ala Gln Thr  Pro Ala Glu Pro Thr  Pro Gly Tyr 
    1775                 1780                 1785             


Glu Val  Gly Gln Arg Lys Arg  Leu Ile Ser Ser Val  Glu Asp Phe 
    1790                 1795                 1800             


Thr Glu  Phe Val 
    1805         


<210>  3
<211>  5424
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleic acid encoding a human TSC2 polypeptide having a S1364A 
       substitution

<400>  3
atggccaaac caacaagcaa agattcaggc ttgaaggaga agtttaagat tctgttggga       60

ctgggaacac cgaggccaaa tcccaggtct gcagagggta aacagacgga gtttatcatc      120

accgcggaaa tactgagaga actgagcatg gaatgtggcc tcaacaatcg catccggatg      180

atagggcaga tttgtgaagt cgcaaaaacc aagaaatttg aagagcacgc agtggaagca      240

ctctggaagg cggtcgcgga tctgttgcag ccggagcggc cgctggaggc ccggcacgcg      300

gtgctggctc tgctgaaggc catcgtgcag gggcagggcg agcgtttggg ggtcctcaga      360

gccctcttct ttaaggtcat caaggattac ccttccaacg aagaccttca cgaaaggctg      420

gaggttttca aggccctcac agacaatggg agacacatca cctacttgga ggaagagctg      480

gctgactttg tcctgcagtg gatggatgtt ggcttgtcct cggaattcct tctggtgctg      540

gtgaacttgg tcaaattcaa tagctgttac ctcgacgagt acatcgcaag gatggttcag      600

atgatctgtc tgctgtgcgt ccggaccgcg tcctctgtgg acatagaggt ctccctgcag      660

gtgctggacg ccgtggtctg ctacaactgc ctgccggctg agagcctccc gctgttcatc      720

gttaccctct gtcgcaccat caacgtcaag gagctctgcg agccttgctg gaagctgatg      780

cggaacctcc ttggcaccca cctgggccac agcgccatct acaacatgtg ccacctcatg      840

gaggacagag cctacatgga ggacgcgccc ctgctgagag gagccgtgtt ttttgtgggc      900

atggctctct ggggagccca ccggctctat tctctcagga actcgccgac atctgtgttg      960

ccatcatttt accaggccat ggcatgtccg aacgaggtgg tgtcctatga gatcgtcctg     1020

tccatcacca ggctcatcaa gaagtatagg aaggagctcc aggtggtggc gtgggacatt     1080

ctgctgaaca tcatcgaacg gctccttcag cagctccaga ccttggacag cccggagctc     1140

aggaccatcg tccatgacct gttgaccacg gtggaggagc tgtgtgacca gaacgagttc     1200

cacgggtctc aggagagata ctttgaactg gtggagagat gtgcggacca gaggcctgag     1260

tcctccctcc tgaacctgat ctcctataga gcgcagtcca tccacccggc caaggacggc     1320

tggattcaga acctgcaggc gctgatggag agattcttca ggagcgagtc ccgaggcgcc     1380

gtgcgcatca aggtgctgga cgtgctgtcc tttgtgctgc tcatcaacag gcagttctat     1440

gaggaggagc tgattaactc agtggtcatc tcgcagctct cccacatccc cgaggataaa     1500

gaccaccagg tccgaaagct ggccacccag ttgctggtgg acctggcaga gggctgccac     1560

acacaccact tcaacagcct gctggacatc atcgagaagg tgatggcccg ctccctctcc     1620

ccacccccgg agctggaaga aagggatgtg gccgcatact cggcctcctt ggaggatgtg     1680

aagacagccg tcctggggct tctggtcatc cttcagacca agctgtacac cctgcctgca     1740

agccacgcca cgcgtgtgta tgagatgctg gtcagccaca ttcagctcca ctacaagcac     1800

agctacaccc tgccaatcgc gagcagcatc cggctgcagg cctttgactt cctgttgctg     1860

ctgcgggccg actcactgca ccgcctgggc ctgcccaaca aggatggagt cgtgcggttc     1920

agcccctact gcgtctgcga ctacatggag ccagagagag gctctgagaa gaagaccagc     1980

ggcccccttt ctcctcccac agggcctcct ggcccggcgc ctgcaggccc cgccgtgcgg     2040

ctggggtccg tgccctactc cctgctcttc cgcgtcctgc tgcagtgctt gaagcaggag     2100

tctgactgga aggtgctgaa gctggttctg ggcaggctgc ctgagtccct gcgctataaa     2160

gtgctcatct ttacttcccc ttgcagtgtg gaccagctgt gctctgctct ctgctccatg     2220

ctttcaggcc caaagacact ggagcggctc cgaggcgccc cagaaggctt ctccagaact     2280

gacttgcacc tggccgtggt tccagtgctg acagcattaa tctcttacca taactacctg     2340

gacaaaacca aacagcgcga gatggtctac tgcctggagc agggcctcat ccaccgctgt     2400

gccagccagt gcgtcgtggc cttgtccatc tgcagcgtgg agatgcctga catcatcatc     2460

aaggcgctgc ctgttctggt ggtgaagctc acgcacatct cagccacagc cagcatggcc     2520

gtcccactgc tggagttcct gtccactctg gccaggctgc cgcacctcta caggaacttt     2580

gccgcggagc agtatgccag tgtgttcgcc atctccctgc cgtacaccaa cccctccaag     2640

tttaatcagt acatcgtgtg tctggcccat cacgtcatag ccatgtggtt catcaggtgc     2700

cgcctgccct tccggaagga ttttgtccct ttcatcacta agggcctgcg gtccaatgtc     2760

ctcttgtctt ttgatgacac ccccgagaag gacagcttca gggcccggag tactagtctc     2820

aacgagagac ccaagagtct gaggatagcc agacccccca aacaaggctt gaataactct     2880

ccacccgtga aagaattcaa ggagagctct gcagccgagg ccttccggtg ccgcagcatc     2940

agtgtgtctg aacatgtggt ccgcagcagg atacagacgt ccctcaccag tgccagcttg     3000

gggtctgcag atgagaactc cgtggcccag gctgacgata gcctgaaaaa cctccacctg     3060

gagctcacgg aaacctgtct ggacatgatg gctcgatacg tcttctccaa cttcacggct     3120

gtcccgaaga ggtctcctgt gggcgagttc ctcctagcgg gtggcaggac caaaacctgg     3180

ctggttggga acaagcttgt cactgtgacg acaagcgtgg gaaccgggac ccggtcgtta     3240

ctaggcctgg actcggggga gctgcagtcc ggcccggagt cgagctccag ccccggggtg     3300

catgtgagac agaccaagga ggcgccggcc aagctggagt cccaggctgg gcagcaggtg     3360

tcccgtgggg cccgggatcg ggtccgttcc atgtcggggg gccatggtct tcgagttggc     3420

gccctggacg tgccggcctc ccagttcctg ggcagtgcca cttctccagg accacggact     3480

gcaccagccg cgaaacctga gaaggcctca gctggcaccc gggttcctgt gcaggagaag     3540

acgaacctgg cggcctatgt gcccctgctg acccagggct gggcggagat cctggtccgg     3600

aggcccacag ggaacaccag ctggctgatg agcctggaga acccgctcag ccctttctcc     3660

tcggacatca acaacatgcc cctgcaggag ctgtctaacg ccctcatggc ggctgagcgc     3720

ttcaaggagc accgggacac agccctgtac aagtcactgt cggtgccggc agccagcacg     3780

gccaaacccc ctcctctgcc tcgctccaac acagtggcct ctttctcctc cctgtaccag     3840

tccagctgcc aaggacagct gcacaggagc gtttcctggg cagactccgc cgtggtcatg     3900

gaggagggaa gtccgggcga ggttcctgtg ctggtggagc ccccagggtt ggaggacgtt     3960

gaggcagcgc taggcatgga caggcgcacg gatgcctaca gcaggtcgtc ctcagtctcc     4020

agccaggagg agaagtcgct ccacgcggag gagctggttg gcaggggcat ccccatcgag     4080

cgagtcgtcg cctcggaggg tggccggccc tctgtggacc tctccttcca gccctcgcag     4140

cccctgagca agtccagctc ctctcccgag ctgcagactc tgcaggacat cctcggggac     4200

cctggggaca aggccgacgt gggccggctg agccctgagg ttaaggcccg gtcacagtca     4260

gggaccctgg acggggaaag tgctgcctgg tcggcctcgg gcgaagacag tcggggccag     4320

cccgagggtc ccttgccttc cagctccccc cgctcgccca gtggcctccg gccccgaggt     4380

tacaccatct ccgactcggc cccatcacgc aggggcaaga gagtagagag ggacgcctta     4440

aagagcagag ccacagcctc caatgcagag aaagtgccag gcatcaaccc cagtttcgtg     4500

ttcctgcagc tctaccattc ccccttcttt ggcgacgagt caaacaagcc aatcctgctg     4560

cccaatgagt cacagtcctt tgagcggtcg gtgcagctcc tcgaccagat cccatcatac     4620

gacacccaca agatcgccgt cctgtatgtt ggagaaggcc agagcaacag cgagctcgcc     4680

atcctgtcca atgagcatgg ctcctacagg tacacggagt tcctgacggg cctgggccgg     4740

ctcatcgagc tgaaggactg ccagccggac aaggtgtacc tgggaggcct ggacgtgtgt     4800

ggtgaggacg gccagttcac ctactgctgg cacgatgaca tcatgcaagc cgtcttccac     4860

atcgccaccc tgatgcccac caaggacgtg gacaagcacc gctgcgacaa gaagcgccac     4920

ctgggcaacg actttgtgtc cattgtctac aatgactccg gtgaggactt caagcttggc     4980

accatcaagg gccagttcaa ctttgtccac gtgatcgtca ccccgctgga ctacgagtgc     5040

aacctggtgt ccctgcagtg caggaaagac atggagggcc ttgtggacac cagcgtggcc     5100

aagatcgtgt ctgaccgcaa cctgcccttc gtggcccgcc agatggccct gcacgcaaat     5160

atggcctcac aggtgcatca tagccgctcc aaccccaccg atatctaccc ctccaagtgg     5220

attgcccggc tccgccacat caagcggctc cgccagcgga tctgcgagga agccgcctac     5280

tccaacccca gcctacctct ggtgcaccct ccgtcccata gcaaagcccc tgcacagact     5340

ccagccgagc ccacacctgg ctatgaggtg ggccagcgga agcgcctcat ctcctcggtg     5400

gaggacttca ccgagtttgt gtga                                            5424


<210>  4
<211>  5424
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  nucleic acid encoding a human TSC2 polypeptide having a S1364E 
       substitution

<400>  4
atggccaaac caacaagcaa agattcaggc ttgaaggaga agtttaagat tctgttggga       60

ctgggaacac cgaggccaaa tcccaggtct gcagagggta aacagacgga gtttatcatc      120

accgcggaaa tactgagaga actgagcatg gaatgtggcc tcaacaatcg catccggatg      180

atagggcaga tttgtgaagt cgcaaaaacc aagaaatttg aagagcacgc agtggaagca      240

ctctggaagg cggtcgcgga tctgttgcag ccggagcggc cgctggaggc ccggcacgcg      300

gtgctggctc tgctgaaggc catcgtgcag gggcagggcg agcgtttggg ggtcctcaga      360

gccctcttct ttaaggtcat caaggattac ccttccaacg aagaccttca cgaaaggctg      420

gaggttttca aggccctcac agacaatggg agacacatca cctacttgga ggaagagctg      480

gctgactttg tcctgcagtg gatggatgtt ggcttgtcct cggaattcct tctggtgctg      540

gtgaacttgg tcaaattcaa tagctgttac ctcgacgagt acatcgcaag gatggttcag      600

atgatctgtc tgctgtgcgt ccggaccgcg tcctctgtgg acatagaggt ctccctgcag      660

gtgctggacg ccgtggtctg ctacaactgc ctgccggctg agagcctccc gctgttcatc      720

gttaccctct gtcgcaccat caacgtcaag gagctctgcg agccttgctg gaagctgatg      780

cggaacctcc ttggcaccca cctgggccac agcgccatct acaacatgtg ccacctcatg      840

gaggacagag cctacatgga ggacgcgccc ctgctgagag gagccgtgtt ttttgtgggc      900

atggctctct ggggagccca ccggctctat tctctcagga actcgccgac atctgtgttg      960

ccatcatttt accaggccat ggcatgtccg aacgaggtgg tgtcctatga gatcgtcctg     1020

tccatcacca ggctcatcaa gaagtatagg aaggagctcc aggtggtggc gtgggacatt     1080

ctgctgaaca tcatcgaacg gctccttcag cagctccaga ccttggacag cccggagctc     1140

aggaccatcg tccatgacct gttgaccacg gtggaggagc tgtgtgacca gaacgagttc     1200

cacgggtctc aggagagata ctttgaactg gtggagagat gtgcggacca gaggcctgag     1260

tcctccctcc tgaacctgat ctcctataga gcgcagtcca tccacccggc caaggacggc     1320

tggattcaga acctgcaggc gctgatggag agattcttca ggagcgagtc ccgaggcgcc     1380

gtgcgcatca aggtgctgga cgtgctgtcc tttgtgctgc tcatcaacag gcagttctat     1440

gaggaggagc tgattaactc agtggtcatc tcgcagctct cccacatccc cgaggataaa     1500

gaccaccagg tccgaaagct ggccacccag ttgctggtgg acctggcaga gggctgccac     1560

acacaccact tcaacagcct gctggacatc atcgagaagg tgatggcccg ctccctctcc     1620

ccacccccgg agctggaaga aagggatgtg gccgcatact cggcctcctt ggaggatgtg     1680

aagacagccg tcctggggct tctggtcatc cttcagacca agctgtacac cctgcctgca     1740

agccacgcca cgcgtgtgta tgagatgctg gtcagccaca ttcagctcca ctacaagcac     1800

agctacaccc tgccaatcgc gagcagcatc cggctgcagg cctttgactt cctgttgctg     1860

ctgcgggccg actcactgca ccgcctgggc ctgcccaaca aggatggagt cgtgcggttc     1920

agcccctact gcgtctgcga ctacatggag ccagagagag gctctgagaa gaagaccagc     1980

ggcccccttt ctcctcccac agggcctcct ggcccggcgc ctgcaggccc cgccgtgcgg     2040

ctggggtccg tgccctactc cctgctcttc cgcgtcctgc tgcagtgctt gaagcaggag     2100

tctgactgga aggtgctgaa gctggttctg ggcaggctgc ctgagtccct gcgctataaa     2160

gtgctcatct ttacttcccc ttgcagtgtg gaccagctgt gctctgctct ctgctccatg     2220

ctttcaggcc caaagacact ggagcggctc cgaggcgccc cagaaggctt ctccagaact     2280

gacttgcacc tggccgtggt tccagtgctg acagcattaa tctcttacca taactacctg     2340

gacaaaacca aacagcgcga gatggtctac tgcctggagc agggcctcat ccaccgctgt     2400

gccagccagt gcgtcgtggc cttgtccatc tgcagcgtgg agatgcctga catcatcatc     2460

aaggcgctgc ctgttctggt ggtgaagctc acgcacatct cagccacagc cagcatggcc     2520

gtcccactgc tggagttcct gtccactctg gccaggctgc cgcacctcta caggaacttt     2580

gccgcggagc agtatgccag tgtgttcgcc atctccctgc cgtacaccaa cccctccaag     2640

tttaatcagt acatcgtgtg tctggcccat cacgtcatag ccatgtggtt catcaggtgc     2700

cgcctgccct tccggaagga ttttgtccct ttcatcacta agggcctgcg gtccaatgtc     2760

ctcttgtctt ttgatgacac ccccgagaag gacagcttca gggcccggag tactagtctc     2820

aacgagagac ccaagagtct gaggatagcc agacccccca aacaaggctt gaataactct     2880

ccacccgtga aagaattcaa ggagagctct gcagccgagg ccttccggtg ccgcagcatc     2940

agtgtgtctg aacatgtggt ccgcagcagg atacagacgt ccctcaccag tgccagcttg     3000

gggtctgcag atgagaactc cgtggcccag gctgacgata gcctgaaaaa cctccacctg     3060

gagctcacgg aaacctgtct ggacatgatg gctcgatacg tcttctccaa cttcacggct     3120

gtcccgaaga ggtctcctgt gggcgagttc ctcctagcgg gtggcaggac caaaacctgg     3180

ctggttggga acaagcttgt cactgtgacg acaagcgtgg gaaccgggac ccggtcgtta     3240

ctaggcctgg actcggggga gctgcagtcc ggcccggagt cgagctccag ccccggggtg     3300

catgtgagac agaccaagga ggcgccggcc aagctggagt cccaggctgg gcagcaggtg     3360

tcccgtgggg cccgggatcg ggtccgttcc atgtcggggg gccatggtct tcgagttggc     3420

gccctggacg tgccggcctc ccagttcctg ggcagtgcca cttctccagg accacggact     3480

gcaccagccg cgaaacctga gaaggcctca gctggcaccc gggttcctgt gcaggagaag     3540

acgaacctgg cggcctatgt gcccctgctg acccagggct gggcggagat cctggtccgg     3600

aggcccacag ggaacaccag ctggctgatg agcctggaga acccgctcag ccctttctcc     3660

tcggacatca acaacatgcc cctgcaggag ctgtctaacg ccctcatggc ggctgagcgc     3720

ttcaaggagc accgggacac agccctgtac aagtcactgt cggtgccggc agccagcacg     3780

gccaaacccc ctcctctgcc tcgctccaac acagtggcct ctttctcctc cctgtaccag     3840

tccagctgcc aaggacagct gcacaggagc gtttcctggg cagactccgc cgtggtcatg     3900

gaggagggaa gtccgggcga ggttcctgtg ctggtggagc ccccagggtt ggaggacgtt     3960

gaggcagcgc taggcatgga caggcgcacg gatgcctaca gcaggtcgtc ctcagtctcc     4020

agccaggagg agaagtcgct ccacgcggag gagctggttg gcaggggcat ccccatcgag     4080

cgagtcgtcg agtcggaggg tggccggccc tctgtggacc tctccttcca gccctcgcag     4140

cccctgagca agtccagctc ctctcccgag ctgcagactc tgcaggacat cctcggggac     4200

cctggggaca aggccgacgt gggccggctg agccctgagg ttaaggcccg gtcacagtca     4260

gggaccctgg acggggaaag tgctgcctgg tcggcctcgg gcgaagacag tcggggccag     4320

cccgagggtc ccttgccttc cagctccccc cgctcgccca gtggcctccg gccccgaggt     4380

tacaccatct ccgactcggc cccatcacgc aggggcaaga gagtagagag ggacgcctta     4440

aagagcagag ccacagcctc caatgcagag aaagtgccag gcatcaaccc cagtttcgtg     4500

ttcctgcagc tctaccattc ccccttcttt ggcgacgagt caaacaagcc aatcctgctg     4560

cccaatgagt cacagtcctt tgagcggtcg gtgcagctcc tcgaccagat cccatcatac     4620

gacacccaca agatcgccgt cctgtatgtt ggagaaggcc agagcaacag cgagctcgcc     4680

atcctgtcca atgagcatgg ctcctacagg tacacggagt tcctgacggg cctgggccgg     4740

ctcatcgagc tgaaggactg ccagccggac aaggtgtacc tgggaggcct ggacgtgtgt     4800

ggtgaggacg gccagttcac ctactgctgg cacgatgaca tcatgcaagc cgtcttccac     4860

atcgccaccc tgatgcccac caaggacgtg gacaagcacc gctgcgacaa gaagcgccac     4920

ctgggcaacg actttgtgtc cattgtctac aatgactccg gtgaggactt caagcttggc     4980

accatcaagg gccagttcaa ctttgtccac gtgatcgtca ccccgctgga ctacgagtgc     5040

aacctggtgt ccctgcagtg caggaaagac atggagggcc ttgtggacac cagcgtggcc     5100

aagatcgtgt ctgaccgcaa cctgcccttc gtggcccgcc agatggccct gcacgcaaat     5160

atggcctcac aggtgcatca tagccgctcc aaccccaccg atatctaccc ctccaagtgg     5220

attgcccggc tccgccacat caagcggctc cgccagcgga tctgcgagga agccgcctac     5280

tccaacccca gcctacctct ggtgcaccct ccgtcccata gcaaagcccc tgcacagact     5340

ccagccgagc ccacacctgg ctatgaggtg ggccagcgga agcgcctcat ctcctcggtg     5400

gaggacttca ccgagtttgt gtga                                            5424


<210>  5
<211>  1807
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


Ile Leu Leu Gly Leu Gly Thr Pro Arg Pro Asn Pro Arg Ser Ala Glu 
            20                  25                  30          


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ala Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Met Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Glu Val Ala Lys Thr Lys Lys Phe Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


Leu Trp Lys Ala Val Ala Asp Leu Leu Gln Pro Glu Arg Pro Leu Glu 
                85                  90                  95      


Ala Arg His Ala Val Leu Ala Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Glu Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Asp Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Arg Met Val Gln Met Ile Cys Leu Leu Cys Val Arg 
        195                 200                 205             


Thr Ala Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Val Thr Leu Cys Arg Thr Ile Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys His Leu Met Glu Asp Arg Ala Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Gln Ala Met Ala Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Val Val Ala Trp Asp Ile Leu Leu Asn Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Thr Leu Asp Ser Pro Glu Leu Arg Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Phe Glu Leu Val Glu Arg Cys Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Ser Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Ala Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Ser Glu Ser Arg Gly Ala Val Arg Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Asn Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Pro Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Val Ala Ala Tyr Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Met Leu Val Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Ser Tyr Thr Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Val Cys Asp Tyr Met Glu Pro Glu Arg Gly Ser Glu 
                645                 650                 655     


Lys Lys Thr Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Gly Pro 
            660                 665                 670         


Ala Pro Ala Gly Pro Ala Val Arg Leu Gly Ser Val Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Ser Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Gly Arg Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Cys Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Gly Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Ala Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Lys 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile His Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ser Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Val Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Ala Ala Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Phe Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Ser Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Pro Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Ser Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Val 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Ser Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Glu Leu Gln Ser  Gly Pro Glu Ser Ser  Ser Ser Pro 
    1085                 1090                 1095             


Gly Val  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Ala Leu Asp 
    1130                 1135                 1140             


Val Pro  Ala Ser Gln Phe Leu  Gly Ser Ala Thr Ser  Pro Gly Pro 
    1145                 1150                 1155             


Arg Thr  Ala Pro Ala Ala Lys  Pro Glu Lys Ala Ser  Ala Gly Thr 
    1160                 1165                 1170             


Arg Val  Pro Val Gln Glu Lys  Thr Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Arg  Asp Thr Ala 
    1235                 1240                 1245             


Leu Tyr  Lys Ser Leu Ser Val  Pro Ala Ala Ser Thr  Ala Lys Pro 
    1250                 1255                 1260             


Pro Pro  Leu Pro Arg Ser Asn  Thr Val Ala Ser Phe  Ser Ser Leu 
    1265                 1270                 1275             


Tyr Gln  Ser Ser Cys Gln Gly  Gln Leu His Arg Ser  Val Ser Trp 
    1280                 1285                 1290             


Ala Asp  Ser Ala Val Val Met  Glu Glu Gly Ser Pro  Gly Glu Val 
    1295                 1300                 1305             


Pro Val  Leu Val Glu Pro Pro  Gly Leu Glu Asp Val  Glu Ala Ala 
    1310                 1315                 1320             


Leu Gly  Met Asp Arg Arg Thr  Asp Ala Tyr Ser Arg  Ser Ser Ser 
    1325                 1330                 1335             


Val Ser  Ser Gln Glu Glu Lys  Ser Leu His Ala Glu  Glu Leu Val 
    1340                 1345                 1350             


Gly Arg  Gly Ile Pro Ile Glu  Arg Val Val Ser Ser  Glu Gly Gly 
    1355                 1360                 1365             


Arg Pro  Ser Val Asp Leu Ser  Phe Gln Pro Ser Gln  Pro Leu Ser 
    1370                 1375                 1380             


Lys Ser  Ser Ser Ser Pro Glu  Leu Gln Thr Leu Gln  Asp Ile Leu 
    1385                 1390                 1395             


Gly Asp  Pro Gly Asp Lys Ala  Asp Val Gly Arg Leu  Ser Pro Glu 
    1400                 1405                 1410             


Val Lys  Ala Arg Ser Gln Ser  Gly Thr Leu Asp Gly  Glu Ser Ala 
    1415                 1420                 1425             


Ala Trp  Ser Ala Ser Gly Glu  Asp Ser Arg Gly Gln  Pro Glu Gly 
    1430                 1435                 1440             


Pro Leu  Pro Ser Ser Ser Pro  Arg Ser Pro Ser Gly  Leu Arg Pro 
    1445                 1450                 1455             


Arg Gly  Tyr Thr Ile Ser Asp  Ser Ala Pro Ser Arg  Arg Gly Lys 
    1460                 1465                 1470             


Arg Val  Glu Arg Asp Ala Leu  Lys Ser Arg Ala Thr  Ala Ser Asn 
    1475                 1480                 1485             


Ala Glu  Lys Val Pro Gly Ile  Asn Pro Ser Phe Val  Phe Leu Gln 
    1490                 1495                 1500             


Leu Tyr  His Ser Pro Phe Phe  Gly Asp Glu Ser Asn  Lys Pro Ile 
    1505                 1510                 1515             


Leu Leu  Pro Asn Glu Ser Gln  Ser Phe Glu Arg Ser  Val Gln Leu 
    1520                 1525                 1530             


Leu Asp  Gln Ile Pro Ser Tyr  Asp Thr His Lys Ile  Ala Val Leu 
    1535                 1540                 1545             


Tyr Val  Gly Glu Gly Gln Ser  Asn Ser Glu Leu Ala  Ile Leu Ser 
    1550                 1555                 1560             


Asn Glu  His Gly Ser Tyr Arg  Tyr Thr Glu Phe Leu  Thr Gly Leu 
    1565                 1570                 1575             


Gly Arg  Leu Ile Glu Leu Lys  Asp Cys Gln Pro Asp  Lys Val Tyr 
    1580                 1585                 1590             


Leu Gly  Gly Leu Asp Val Cys  Gly Glu Asp Gly Gln  Phe Thr Tyr 
    1595                 1600                 1605             


Cys Trp  His Asp Asp Ile Met  Gln Ala Val Phe His  Ile Ala Thr 
    1610                 1615                 1620             


Leu Met  Pro Thr Lys Asp Val  Asp Lys His Arg Cys  Asp Lys Lys 
    1625                 1630                 1635             


Arg His  Leu Gly Asn Asp Phe  Val Ser Ile Val Tyr  Asn Asp Ser 
    1640                 1645                 1650             


Gly Glu  Asp Phe Lys Leu Gly  Thr Ile Lys Gly Gln  Phe Asn Phe 
    1655                 1660                 1665             


Val His  Val Ile Val Thr Pro  Leu Asp Tyr Glu Cys  Asn Leu Val 
    1670                 1675                 1680             


Ser Leu  Gln Cys Arg Lys Asp  Met Glu Gly Leu Val  Asp Thr Ser 
    1685                 1690                 1695             


Val Ala  Lys Ile Val Ser Asp  Arg Asn Leu Pro Phe  Val Ala Arg 
    1700                 1705                 1710             


Gln Met  Ala Leu His Ala Asn  Met Ala Ser Gln Val  His His Ser 
    1715                 1720                 1725             


Arg Ser  Asn Pro Thr Asp Ile  Tyr Pro Ser Lys Trp  Ile Ala Arg 
    1730                 1735                 1740             


Leu Arg  His Ile Lys Arg Leu  Arg Gln Arg Ile Cys  Glu Glu Ala 
    1745                 1750                 1755             


Ala Tyr  Ser Asn Pro Ser Leu  Pro Leu Val His Pro  Pro Ser His 
    1760                 1765                 1770             


Ser Lys  Ala Pro Ala Gln Thr  Pro Ala Glu Pro Thr  Pro Gly Tyr 
    1775                 1780                 1785             


Glu Val  Gly Gln Arg Lys Arg  Leu Ile Ser Ser Val  Glu Asp Phe 
    1790                 1795                 1800             


Thr Glu  Phe Val 
    1805         


<210>  6
<211>  1814
<212>  PRT
<213>  Mus musculus

<400>  6

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


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


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ser Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Gly Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Asp Val Ala Lys Thr Lys Lys Leu Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


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


Ala Arg His Ala Val Leu Thr Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Asp Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Glu Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Ser Met Val His Met Ile Cys Leu Leu Cys Ile Arg 
        195                 200                 205             


Thr Val Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Ile Thr Leu Cys Arg Thr Ile Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys Arg Ile Met Glu Asp Arg Ser Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Glu Ala Met Thr Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Ala Val Thr Trp Asp Ile Leu Leu Asp Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Asn Leu Asp Ser Pro Glu Leu Lys Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Tyr Glu Leu Val Glu Ser Tyr Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Ser Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Leu Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Asn Glu Cys Arg Ser Ala Val Ala Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Ile Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Pro Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Leu Ala Val His Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Ser Leu Ile Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Gly Tyr Ser Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Leu Cys Asp Cys Met Glu Leu Asp Arg Ala Ser Glu 
                645                 650                 655     


Lys Lys Ala Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Ser Pro 
            660                 665                 670         


Val Pro Met Gly Pro Ala Val Arg Leu Gly Tyr Leu Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Ser Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Ser Arg Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Ser Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Ala Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Thr Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Arg 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile Tyr Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ala Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Ile Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Val Pro Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Tyr Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Ser Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Ala Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Cys Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Met 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Asn Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Asp Leu Gln Gly  Gly Ser Asp Ser Ser  Ser Asp Pro 
    1085                 1090                 1095             


Ser Thr  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Val Leu Asp 
    1130                 1135                 1140             


Thr Ser  Ala Pro Tyr Ser Pro  Gly Gly Ser Ala Ser  Leu Gly Pro 
    1145                 1150                 1155             


Gln Thr  Ala Val Ala Ala Lys  Pro Glu Lys Pro Pro  Ala Gly Ala 
    1160                 1165                 1170             


Gln Leu  Pro Thr Ala Glu Lys  Thr Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Gly  His Ala Pro 
    1235                 1240                 1245             


Val Gln  Val Ile Val Ser Ala  Thr Gly Cys Thr Ala  Lys Pro Pro 
    1250                 1255                 1260             


Thr Leu  Pro Arg Ser Asn Thr  Val Ala Ser Phe Ser  Ser Leu Tyr 
    1265                 1270                 1275             


Gln Pro  Ser Cys Gln Gly Gln  Leu His Arg Ser Val  Ser Trp Ala 
    1280                 1285                 1290             


Asp Ser  Ala Met Val Leu Glu  Glu Gly Ser Pro Gly  Glu Thr Gln 
    1295                 1300                 1305             


Val Pro  Val Glu Pro Pro Glu  Leu Glu Asp Phe Glu  Ala Ala Leu 
    1310                 1315                 1320             


Gly Thr  Asp Arg His Cys Gln  Arg Pro Asp Thr Tyr  Ser Arg Ser 
    1325                 1330                 1335             


Ser Ser  Ala Ser Ser Gln Glu  Glu Lys Ser His Leu  Glu Glu Leu 
    1340                 1345                 1350             


Ala Ala  Gly Gly Ile Pro Ile  Glu Arg Ala Ile Ser  Ser Glu Gly 
    1355                 1360                 1365             


Ala Arg  Pro Ala Val Asp Leu  Ser Phe Gln Pro Ser  Gln Pro Leu 
    1370                 1375                 1380             


Ser Lys  Ser Ser Ser Ser Pro  Glu Leu Gln Thr Leu  Gln Asp Ile 
    1385                 1390                 1395             


Leu Gly  Asp Leu Gly Asp Lys  Ile Asp Ile Gly Arg  Leu Ser Pro 
    1400                 1405                 1410             


Glu Ala  Lys Val Arg Ser Gln  Ser Gly Ile Leu Asp  Gly Glu Ala 
    1415                 1420                 1425             


Ala Thr  Trp Ser Ala Thr Gly  Glu Glu Ser Arg Ile  Thr Val Pro 
    1430                 1435                 1440             


Pro Glu  Gly Pro Leu Pro Ser  Ser Ser Pro Arg Ser  Pro Ser Gly 
    1445                 1450                 1455             


Leu Arg  Pro Arg Gly Tyr Thr  Ile Ser Asp Ser Ala  Pro Ser Arg 
    1460                 1465                 1470             


Arg Gly  Lys Arg Val Glu Arg  Asp Asn Phe Lys Ser  Arg Ala Ala 
    1475                 1480                 1485             


Ala Ser  Ser Ala Glu Lys Val  Pro Gly Ile Asn Pro  Ser Phe Val 
    1490                 1495                 1500             


Phe Leu  Gln Leu Tyr His Ser  Pro Phe Phe Gly Asp  Glu Ser Asn 
    1505                 1510                 1515             


Lys Pro  Ile Leu Leu Pro Asn  Glu Ser Phe Glu Arg  Ser Val Gln 
    1520                 1525                 1530             


Leu Leu  Asp Gln Ile Pro Ser  Tyr Asp Thr His Lys  Ile Ala Val 
    1535                 1540                 1545             


Leu Tyr  Val Gly Glu Gly Gln  Ser Ser Ser Glu Leu  Ala Ile Leu 
    1550                 1555                 1560             


Ser Asn  Glu His Gly Ser Tyr  Arg Tyr Thr Glu Phe  Leu Thr Gly 
    1565                 1570                 1575             


Leu Gly  Arg Leu Ile Glu Leu  Lys Asp Cys Gln Pro  Asp Lys Val 
    1580                 1585                 1590             


Tyr Leu  Gly Gly Leu Asp Val  Cys Gly Glu Asp Gly  Gln Phe Thr 
    1595                 1600                 1605             


Tyr Cys  Trp His Asp Asp Ile  Met Gln Ala Val Phe  His Ile Ala 
    1610                 1615                 1620             


Thr Leu  Met Pro Thr Lys Asp  Val Asp Lys His Arg  Cys Asp Lys 
    1625                 1630                 1635             


Lys Arg  His Leu Gly Asn Asp  Phe Val Ser Ile Ile  Tyr Asn Asp 
    1640                 1645                 1650             


Ser Gly  Glu Asp Phe Lys Leu  Gly Thr Ile Lys Gln  Gly Gln Phe 
    1655                 1660                 1665             


Asn Phe  Val His Val Ile Ile  Thr Pro Leu Asp Tyr  Lys Cys Asn 
    1670                 1675                 1680             


Leu Leu  Thr Leu Gln Cys Arg  Lys Asp Gly Pro Ala  Cys Lys Cys 
    1685                 1690                 1695             


Glu Trp  Trp Arg Gln Pro Gly  Glu Ile Val Val Trp  Ala Leu Pro 
    1700                 1705                 1710             


Val Val  Met Glu Leu Thr Val  Thr Ile Leu Leu Cys  His Leu Gln 
    1715                 1720                 1725             


Met Ala  Ser Gln Val His His  Ser Arg Ser Asn Pro  Thr Asp Ile 
    1730                 1735                 1740             


Tyr Pro  Ser Lys Trp Ile Ala  Arg Leu Arg His Ile  Lys Arg Leu 
    1745                 1750                 1755             


Arg Gln  Arg Ile Arg Glu Glu  Val His Tyr Ser Asn  Pro Ser Leu 
    1760                 1765                 1770             


Pro Leu  Met His Pro Pro Ala  His Thr Lys Ala Pro  Ala Gln Ala 
    1775                 1780                 1785             


Pro Glu  Ala Thr Pro Thr Tyr  Glu Thr Gly Gln Arg  Lys Arg Leu 
    1790                 1795                 1800             


Ile Ser  Ser Val Asp Asp Phe  Thr Glu Phe Val 
    1805                 1810                 


<210>  7
<211>  1809
<212>  PRT
<213>  Rattus norvegicus

<400>  7

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


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


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ala Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Gly Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Asp Val Ala Lys Thr Lys Lys Leu Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


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


Ala Arg His Ala Val Leu Ala Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Asp Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Glu Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Pro Met Val His Met Ile Cys Leu Leu Cys Ile Arg 
        195                 200                 205             


Thr Val Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Ile Thr Leu Cys Arg Thr Val Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys Arg Ile Met Glu Asn Arg Ser Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Glu Ala Met Thr Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Ala Val Thr Trp Asp Ile Leu Leu Asp Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Asn Leu Asp Ser Pro Glu Leu Arg Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Tyr Glu Leu Val Glu Ser Tyr Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Thr Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Leu Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Asn Glu Cys Arg Ser Ala Val Arg Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Asn Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Leu Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Leu Ala Val Tyr Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Thr Leu Ile Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Gly Tyr Ser Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Leu Cys Asp Cys Ala Glu Leu Asp Arg Ala Ser Glu 
                645                 650                 655     


Lys Lys Ala Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Ser Pro 
            660                 665                 670         


Val Pro Thr Gly Pro Ala Val Arg Leu Gly His Leu Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Thr Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Ser Lys Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Ser Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Ala Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Thr Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Arg 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile Tyr Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ala Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Ile Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Ala Ala Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Tyr Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Lys Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Ala Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Cys Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Met 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Asn Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Asp Leu Gln Gly  Gly Ser Ala Ser Ser  Ser Asp Pro 
    1085                 1090                 1095             


Gly Thr  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Val Leu Asp 
    1130                 1135                 1140             


Thr Ser  Ala Pro Tyr Thr Pro  Gly Gly Pro Ala Ser  Leu Gly Ala 
    1145                 1150                 1155             


Gln Ala  Ala Pro Ala Ala Arg  Pro Glu Lys Pro Cys  Ala Gly Ala 
    1160                 1165                 1170             


Gln Leu  Pro Ala Ala Glu Lys  Ala Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Arg  Asp Thr Ala 
    1235                 1240                 1245             


Leu Tyr  Lys Ser Leu Ser Val  Pro Ala Ala Gly Thr  Ala Lys Pro 
    1250                 1255                 1260             


Pro Thr  Leu Pro Arg Ser Asn  Thr Val Ala Ser Phe  Ser Ser Leu 
    1265                 1270                 1275             


Tyr Gln  Pro Ser Cys Gln Gly  Gln Leu His Arg Ser  Val Ser Trp 
    1280                 1285                 1290             


Ala Asp  Ser Ala Val Val Leu  Glu Glu Gly Ser Pro  Gly Glu Ala 
    1295                 1300                 1305             


His Val  Pro Val Glu Pro Pro  Glu Leu Glu Asp Phe  Glu Ala Ala 
    1310                 1315                 1320             


Leu Gly  Thr Asp Arg His Cys  Gln Arg Pro Asp Ala  Tyr Ser Arg 
    1325                 1330                 1335             


Ser Ser  Ser Ala Ser Ser Gln  Glu Glu Lys Ser His  Leu Glu Glu 
    1340                 1345                 1350             


Leu Ala  Ala Gly Gly Ile Pro  Ile Glu Arg Ala Ile  Ser Ser Glu 
    1355                 1360                 1365             


Gly Ala  Arg Pro Thr Val Asp  Leu Ser Phe Gln Pro  Ser Gln Pro 
    1370                 1375                 1380             


Leu Ser  Lys Ser Ser Ser Ser  Pro Glu Leu Gln Thr  Leu Gln Asp 
    1385                 1390                 1395             


Ile Leu  Gly Asp Leu Gly Asp  Lys Thr Asp Ile Gly  Arg Leu Ser 
    1400                 1405                 1410             


Pro Glu  Ala Lys Val Arg Ser  Gln Ser Gly Ile Leu  Asp Gly Glu 
    1415                 1420                 1425             


Ala Ala  Thr Trp Ser Ala Pro  Gly Glu Glu Ser Arg  Ile Thr Val 
    1430                 1435                 1440             


Pro Pro  Glu Gly Pro Leu Pro  Ser Ser Ser Pro Arg  Ser Pro Ser 
    1445                 1450                 1455             


Gly Leu  Arg Pro Arg Gly Tyr  Thr Ile Ser Asp Ser  Ala Pro Ser 
    1460                 1465                 1470             


Arg Arg  Gly Lys Arg Val Glu  Arg Asp Asn Phe Lys  Ser Arg Thr 
    1475                 1480                 1485             


Ala Ala  Ser Ser Ala Glu Lys  Val Pro Gly Ile Asn  Pro Ser Phe 
    1490                 1495                 1500             


Val Phe  Leu Gln Leu Tyr His  Ser Pro Phe Cys Gly  Asp Glu Ser 
    1505                 1510                 1515             


Asn Lys  Pro Ile Leu Leu Pro  Asn Glu Ser Phe Glu  Arg Ser Val 
    1520                 1525                 1530             


Gln Leu  Leu Asp Gln Ile Pro  Ser Tyr Asp Thr His  Lys Ile Ala 
    1535                 1540                 1545             


Val Leu  Tyr Val Gly Glu Gly  Gln Ser Ser Ser Glu  Leu Ala Ile 
    1550                 1555                 1560             


Leu Ser  Asn Glu His Gly Ser  Tyr Arg Tyr Thr Glu  Phe Leu Thr 
    1565                 1570                 1575             


Gly Leu  Gly Arg Leu Ile Glu  Leu Lys Asp Cys Gln  Pro Asp Lys 
    1580                 1585                 1590             


Val Tyr  Leu Gly Gly Leu Asp  Val Cys Gly Glu Asp  Gly Gln Phe 
    1595                 1600                 1605             


Thr Tyr  Cys Trp His Asp Asp  Ile Met Gln Ala Val  Phe His Ile 
    1610                 1615                 1620             


Ala Thr  Leu Met Pro Thr Lys  Asp Val Asp Lys His  Arg Cys Asp 
    1625                 1630                 1635             


Lys Lys  Arg His Leu Gly Asn  Asp Phe Val Ser Ile  Ile Tyr Asn 
    1640                 1645                 1650             


Asp Ser  Gly Glu Asp Phe Lys  Leu Gly Thr Ile Lys  Gly Gln Phe 
    1655                 1660                 1665             


Asn Phe  Val His Val Ile Ile  Thr Pro Leu Asp Tyr  Lys Cys Asn 
    1670                 1675                 1680             


Leu Leu  Thr Leu Gln Cys Arg  Lys Asp Met Glu Gly  Leu Val Asp 
    1685                 1690                 1695             


Thr Ser  Val Ala Lys Ile Val  Ser Asp Arg Asn Leu  Ser Phe Val 
    1700                 1705                 1710             


Ala Arg  Gln Met Ala Leu His  Ala Asn Met Ala Ser  Gln Val His 
    1715                 1720                 1725             


His Arg  Arg Ser Asn Pro Thr  Asp Ile Tyr Pro Ser  Lys Trp Ile 
    1730                 1735                 1740             


Ala Arg  Leu Arg His Ile Lys  Arg Leu Arg Gln Arg  Ile Arg Glu 
    1745                 1750                 1755             


Glu Val  His Tyr Ser Asn Pro  Ser Leu Pro Leu Met  His Pro Pro 
    1760                 1765                 1770             


Ala His  Thr Lys Val Pro Ala  Gln Ala Pro Thr Glu  Ala Thr Pro 
    1775                 1780                 1785             


Thr Tyr  Glu Thr Gly Gln Arg  Lys Arg Leu Ile Ser  Ser Val Asp 
    1790                 1795                 1800             


Asp Phe  Thr Glu Phe Val 
    1805                 


<210>  8
<211>  1814
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mouse TSC2 polypeptide having a S1365A substitution

<400>  8

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


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


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ser Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Gly Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Asp Val Ala Lys Thr Lys Lys Leu Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


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


Ala Arg His Ala Val Leu Thr Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Asp Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Glu Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Ser Met Val His Met Ile Cys Leu Leu Cys Ile Arg 
        195                 200                 205             


Thr Val Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Ile Thr Leu Cys Arg Thr Ile Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys Arg Ile Met Glu Asp Arg Ser Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Glu Ala Met Thr Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Ala Val Thr Trp Asp Ile Leu Leu Asp Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Asn Leu Asp Ser Pro Glu Leu Lys Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Tyr Glu Leu Val Glu Ser Tyr Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Ser Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Leu Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Asn Glu Cys Arg Ser Ala Val Ala Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Ile Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Pro Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Leu Ala Val His Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Ser Leu Ile Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Gly Tyr Ser Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Leu Cys Asp Cys Met Glu Leu Asp Arg Ala Ser Glu 
                645                 650                 655     


Lys Lys Ala Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Ser Pro 
            660                 665                 670         


Val Pro Met Gly Pro Ala Val Arg Leu Gly Tyr Leu Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Ser Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Ser Arg Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Ser Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Ala Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Thr Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Arg 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile Tyr Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ala Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Ile Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Val Pro Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Tyr Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Ser Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Ala Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Cys Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Met 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Asn Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Asp Leu Gln Gly  Gly Ser Asp Ser Ser  Ser Asp Pro 
    1085                 1090                 1095             


Ser Thr  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Val Leu Asp 
    1130                 1135                 1140             


Thr Ser  Ala Pro Tyr Ser Pro  Gly Gly Ser Ala Ser  Leu Gly Pro 
    1145                 1150                 1155             


Gln Thr  Ala Val Ala Ala Lys  Pro Glu Lys Pro Pro  Ala Gly Ala 
    1160                 1165                 1170             


Gln Leu  Pro Thr Ala Glu Lys  Thr Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Gly  His Ala Pro 
    1235                 1240                 1245             


Val Gln  Val Ile Val Ser Ala  Thr Gly Cys Thr Ala  Lys Pro Pro 
    1250                 1255                 1260             


Thr Leu  Pro Arg Ser Asn Thr  Val Ala Ser Phe Ser  Ser Leu Tyr 
    1265                 1270                 1275             


Gln Pro  Ser Cys Gln Gly Gln  Leu His Arg Ser Val  Ser Trp Ala 
    1280                 1285                 1290             


Asp Ser  Ala Met Val Leu Glu  Glu Gly Ser Pro Gly  Glu Thr Gln 
    1295                 1300                 1305             


Val Pro  Val Glu Pro Pro Glu  Leu Glu Asp Phe Glu  Ala Ala Leu 
    1310                 1315                 1320             


Gly Thr  Asp Arg His Cys Gln  Arg Pro Asp Thr Tyr  Ser Arg Ser 
    1325                 1330                 1335             


Ser Ser  Ala Ser Ser Gln Glu  Glu Lys Ser His Leu  Glu Glu Leu 
    1340                 1345                 1350             


Ala Ala  Gly Gly Ile Pro Ile  Glu Arg Ala Ile Ala  Ser Glu Gly 
    1355                 1360                 1365             


Ala Arg  Pro Ala Val Asp Leu  Ser Phe Gln Pro Ser  Gln Pro Leu 
    1370                 1375                 1380             


Ser Lys  Ser Ser Ser Ser Pro  Glu Leu Gln Thr Leu  Gln Asp Ile 
    1385                 1390                 1395             


Leu Gly  Asp Leu Gly Asp Lys  Ile Asp Ile Gly Arg  Leu Ser Pro 
    1400                 1405                 1410             


Glu Ala  Lys Val Arg Ser Gln  Ser Gly Ile Leu Asp  Gly Glu Ala 
    1415                 1420                 1425             


Ala Thr  Trp Ser Ala Thr Gly  Glu Glu Ser Arg Ile  Thr Val Pro 
    1430                 1435                 1440             


Pro Glu  Gly Pro Leu Pro Ser  Ser Ser Pro Arg Ser  Pro Ser Gly 
    1445                 1450                 1455             


Leu Arg  Pro Arg Gly Tyr Thr  Ile Ser Asp Ser Ala  Pro Ser Arg 
    1460                 1465                 1470             


Arg Gly  Lys Arg Val Glu Arg  Asp Asn Phe Lys Ser  Arg Ala Ala 
    1475                 1480                 1485             


Ala Ser  Ser Ala Glu Lys Val  Pro Gly Ile Asn Pro  Ser Phe Val 
    1490                 1495                 1500             


Phe Leu  Gln Leu Tyr His Ser  Pro Phe Phe Gly Asp  Glu Ser Asn 
    1505                 1510                 1515             


Lys Pro  Ile Leu Leu Pro Asn  Glu Ser Phe Glu Arg  Ser Val Gln 
    1520                 1525                 1530             


Leu Leu  Asp Gln Ile Pro Ser  Tyr Asp Thr His Lys  Ile Ala Val 
    1535                 1540                 1545             


Leu Tyr  Val Gly Glu Gly Gln  Ser Ser Ser Glu Leu  Ala Ile Leu 
    1550                 1555                 1560             


Ser Asn  Glu His Gly Ser Tyr  Arg Tyr Thr Glu Phe  Leu Thr Gly 
    1565                 1570                 1575             


Leu Gly  Arg Leu Ile Glu Leu  Lys Asp Cys Gln Pro  Asp Lys Val 
    1580                 1585                 1590             


Tyr Leu  Gly Gly Leu Asp Val  Cys Gly Glu Asp Gly  Gln Phe Thr 
    1595                 1600                 1605             


Tyr Cys  Trp His Asp Asp Ile  Met Gln Ala Val Phe  His Ile Ala 
    1610                 1615                 1620             


Thr Leu  Met Pro Thr Lys Asp  Val Asp Lys His Arg  Cys Asp Lys 
    1625                 1630                 1635             


Lys Arg  His Leu Gly Asn Asp  Phe Val Ser Ile Ile  Tyr Asn Asp 
    1640                 1645                 1650             


Ser Gly  Glu Asp Phe Lys Leu  Gly Thr Ile Lys Gln  Gly Gln Phe 
    1655                 1660                 1665             


Asn Phe  Val His Val Ile Ile  Thr Pro Leu Asp Tyr  Lys Cys Asn 
    1670                 1675                 1680             


Leu Leu  Thr Leu Gln Cys Arg  Lys Asp Gly Pro Ala  Cys Lys Cys 
    1685                 1690                 1695             


Glu Trp  Trp Arg Gln Pro Gly  Glu Ile Val Val Trp  Ala Leu Pro 
    1700                 1705                 1710             


Val Val  Met Glu Leu Thr Val  Thr Ile Leu Leu Cys  His Leu Gln 
    1715                 1720                 1725             


Met Ala  Ser Gln Val His His  Ser Arg Ser Asn Pro  Thr Asp Ile 
    1730                 1735                 1740             


Tyr Pro  Ser Lys Trp Ile Ala  Arg Leu Arg His Ile  Lys Arg Leu 
    1745                 1750                 1755             


Arg Gln  Arg Ile Arg Glu Glu  Val His Tyr Ser Asn  Pro Ser Leu 
    1760                 1765                 1770             


Pro Leu  Met His Pro Pro Ala  His Thr Lys Ala Pro  Ala Gln Ala 
    1775                 1780                 1785             


Pro Glu  Ala Thr Pro Thr Tyr  Glu Thr Gly Gln Arg  Lys Arg Leu 
    1790                 1795                 1800             


Ile Ser  Ser Val Asp Asp Phe  Thr Glu Phe Val 
    1805                 1810                 


<210>  9
<211>  1809
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rat TSC2 polypeptide having a S1366A substitution

<400>  9

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


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


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ala Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Gly Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Asp Val Ala Lys Thr Lys Lys Leu Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


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


Ala Arg His Ala Val Leu Ala Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Asp Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Glu Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Pro Met Val His Met Ile Cys Leu Leu Cys Ile Arg 
        195                 200                 205             


Thr Val Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Ile Thr Leu Cys Arg Thr Val Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys Arg Ile Met Glu Asn Arg Ser Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Glu Ala Met Thr Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Ala Val Thr Trp Asp Ile Leu Leu Asp Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Asn Leu Asp Ser Pro Glu Leu Arg Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Tyr Glu Leu Val Glu Ser Tyr Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Thr Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Leu Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Asn Glu Cys Arg Ser Ala Val Arg Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Asn Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Leu Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Leu Ala Val Tyr Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Thr Leu Ile Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Gly Tyr Ser Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Leu Cys Asp Cys Ala Glu Leu Asp Arg Ala Ser Glu 
                645                 650                 655     


Lys Lys Ala Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Ser Pro 
            660                 665                 670         


Val Pro Thr Gly Pro Ala Val Arg Leu Gly His Leu Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Thr Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Ser Lys Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Ser Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Ala Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Thr Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Arg 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile Tyr Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ala Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Ile Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Ala Ala Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Tyr Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Lys Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Ala Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Cys Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Met 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Asn Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Asp Leu Gln Gly  Gly Ser Ala Ser Ser  Ser Asp Pro 
    1085                 1090                 1095             


Gly Thr  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Val Leu Asp 
    1130                 1135                 1140             


Thr Ser  Ala Pro Tyr Thr Pro  Gly Gly Pro Ala Ser  Leu Gly Ala 
    1145                 1150                 1155             


Gln Ala  Ala Pro Ala Ala Arg  Pro Glu Lys Pro Cys  Ala Gly Ala 
    1160                 1165                 1170             


Gln Leu  Pro Ala Ala Glu Lys  Ala Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Arg  Asp Thr Ala 
    1235                 1240                 1245             


Leu Tyr  Lys Ser Leu Ser Val  Pro Ala Ala Gly Thr  Ala Lys Pro 
    1250                 1255                 1260             


Pro Thr  Leu Pro Arg Ser Asn  Thr Val Ala Ser Phe  Ser Ser Leu 
    1265                 1270                 1275             


Tyr Gln  Pro Ser Cys Gln Gly  Gln Leu His Arg Ser  Val Ser Trp 
    1280                 1285                 1290             


Ala Asp  Ser Ala Val Val Leu  Glu Glu Gly Ser Pro  Gly Glu Ala 
    1295                 1300                 1305             


His Val  Pro Val Glu Pro Pro  Glu Leu Glu Asp Phe  Glu Ala Ala 
    1310                 1315                 1320             


Leu Gly  Thr Asp Arg His Cys  Gln Arg Pro Asp Ala  Tyr Ser Arg 
    1325                 1330                 1335             


Ser Ser  Ser Ala Ser Ser Gln  Glu Glu Lys Ser His  Leu Glu Glu 
    1340                 1345                 1350             


Leu Ala  Ala Gly Gly Ile Pro  Ile Glu Arg Ala Ile  Ala Ser Glu 
    1355                 1360                 1365             


Gly Ala  Arg Pro Thr Val Asp  Leu Ser Phe Gln Pro  Ser Gln Pro 
    1370                 1375                 1380             


Leu Ser  Lys Ser Ser Ser Ser  Pro Glu Leu Gln Thr  Leu Gln Asp 
    1385                 1390                 1395             


Ile Leu  Gly Asp Leu Gly Asp  Lys Thr Asp Ile Gly  Arg Leu Ser 
    1400                 1405                 1410             


Pro Glu  Ala Lys Val Arg Ser  Gln Ser Gly Ile Leu  Asp Gly Glu 
    1415                 1420                 1425             


Ala Ala  Thr Trp Ser Ala Pro  Gly Glu Glu Ser Arg  Ile Thr Val 
    1430                 1435                 1440             


Pro Pro  Glu Gly Pro Leu Pro  Ser Ser Ser Pro Arg  Ser Pro Ser 
    1445                 1450                 1455             


Gly Leu  Arg Pro Arg Gly Tyr  Thr Ile Ser Asp Ser  Ala Pro Ser 
    1460                 1465                 1470             


Arg Arg  Gly Lys Arg Val Glu  Arg Asp Asn Phe Lys  Ser Arg Thr 
    1475                 1480                 1485             


Ala Ala  Ser Ser Ala Glu Lys  Val Pro Gly Ile Asn  Pro Ser Phe 
    1490                 1495                 1500             


Val Phe  Leu Gln Leu Tyr His  Ser Pro Phe Cys Gly  Asp Glu Ser 
    1505                 1510                 1515             


Asn Lys  Pro Ile Leu Leu Pro  Asn Glu Ser Phe Glu  Arg Ser Val 
    1520                 1525                 1530             


Gln Leu  Leu Asp Gln Ile Pro  Ser Tyr Asp Thr His  Lys Ile Ala 
    1535                 1540                 1545             


Val Leu  Tyr Val Gly Glu Gly  Gln Ser Ser Ser Glu  Leu Ala Ile 
    1550                 1555                 1560             


Leu Ser  Asn Glu His Gly Ser  Tyr Arg Tyr Thr Glu  Phe Leu Thr 
    1565                 1570                 1575             


Gly Leu  Gly Arg Leu Ile Glu  Leu Lys Asp Cys Gln  Pro Asp Lys 
    1580                 1585                 1590             


Val Tyr  Leu Gly Gly Leu Asp  Val Cys Gly Glu Asp  Gly Gln Phe 
    1595                 1600                 1605             


Thr Tyr  Cys Trp His Asp Asp  Ile Met Gln Ala Val  Phe His Ile 
    1610                 1615                 1620             


Ala Thr  Leu Met Pro Thr Lys  Asp Val Asp Lys His  Arg Cys Asp 
    1625                 1630                 1635             


Lys Lys  Arg His Leu Gly Asn  Asp Phe Val Ser Ile  Ile Tyr Asn 
    1640                 1645                 1650             


Asp Ser  Gly Glu Asp Phe Lys  Leu Gly Thr Ile Lys  Gly Gln Phe 
    1655                 1660                 1665             


Asn Phe  Val His Val Ile Ile  Thr Pro Leu Asp Tyr  Lys Cys Asn 
    1670                 1675                 1680             


Leu Leu  Thr Leu Gln Cys Arg  Lys Asp Met Glu Gly  Leu Val Asp 
    1685                 1690                 1695             


Thr Ser  Val Ala Lys Ile Val  Ser Asp Arg Asn Leu  Ser Phe Val 
    1700                 1705                 1710             


Ala Arg  Gln Met Ala Leu His  Ala Asn Met Ala Ser  Gln Val His 
    1715                 1720                 1725             


His Arg  Arg Ser Asn Pro Thr  Asp Ile Tyr Pro Ser  Lys Trp Ile 
    1730                 1735                 1740             


Ala Arg  Leu Arg His Ile Lys  Arg Leu Arg Gln Arg  Ile Arg Glu 
    1745                 1750                 1755             


Glu Val  His Tyr Ser Asn Pro  Ser Leu Pro Leu Met  His Pro Pro 
    1760                 1765                 1770             


Ala His  Thr Lys Val Pro Ala  Gln Ala Pro Thr Glu  Ala Thr Pro 
    1775                 1780                 1785             


Thr Tyr  Glu Thr Gly Gln Arg  Lys Arg Leu Ile Ser  Ser Val Asp 
    1790                 1795                 1800             


Asp Phe  Thr Glu Phe Val 
    1805                 


<210>  10
<211>  1814
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mouse TSC2 polypeptide having a S1364E substitution

<400>  10

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


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


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ser Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Gly Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Asp Val Ala Lys Thr Lys Lys Leu Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


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


Ala Arg His Ala Val Leu Thr Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Asp Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Glu Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Ser Met Val His Met Ile Cys Leu Leu Cys Ile Arg 
        195                 200                 205             


Thr Val Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Ile Thr Leu Cys Arg Thr Ile Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys Arg Ile Met Glu Asp Arg Ser Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Glu Ala Met Thr Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Ala Val Thr Trp Asp Ile Leu Leu Asp Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Asn Leu Asp Ser Pro Glu Leu Lys Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Tyr Glu Leu Val Glu Ser Tyr Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Ser Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Leu Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Asn Glu Cys Arg Ser Ala Val Ala Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Ile Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Pro Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Leu Ala Val His Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Ser Leu Ile Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Gly Tyr Ser Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Leu Cys Asp Cys Met Glu Leu Asp Arg Ala Ser Glu 
                645                 650                 655     


Lys Lys Ala Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Ser Pro 
            660                 665                 670         


Val Pro Met Gly Pro Ala Val Arg Leu Gly Tyr Leu Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Ser Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Ser Arg Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Ser Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Ala Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Thr Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Arg 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile Tyr Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ala Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Ile Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Val Pro Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Tyr Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Ser Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Ala Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Cys Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Met 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Asn Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Asp Leu Gln Gly  Gly Ser Asp Ser Ser  Ser Asp Pro 
    1085                 1090                 1095             


Ser Thr  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Val Leu Asp 
    1130                 1135                 1140             


Thr Ser  Ala Pro Tyr Ser Pro  Gly Gly Ser Ala Ser  Leu Gly Pro 
    1145                 1150                 1155             


Gln Thr  Ala Val Ala Ala Lys  Pro Glu Lys Pro Pro  Ala Gly Ala 
    1160                 1165                 1170             


Gln Leu  Pro Thr Ala Glu Lys  Thr Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Gly  His Ala Pro 
    1235                 1240                 1245             


Val Gln  Val Ile Val Ser Ala  Thr Gly Cys Thr Ala  Lys Pro Pro 
    1250                 1255                 1260             


Thr Leu  Pro Arg Ser Asn Thr  Val Ala Ser Phe Ser  Ser Leu Tyr 
    1265                 1270                 1275             


Gln Pro  Ser Cys Gln Gly Gln  Leu His Arg Ser Val  Ser Trp Ala 
    1280                 1285                 1290             


Asp Ser  Ala Met Val Leu Glu  Glu Gly Ser Pro Gly  Glu Thr Gln 
    1295                 1300                 1305             


Val Pro  Val Glu Pro Pro Glu  Leu Glu Asp Phe Glu  Ala Ala Leu 
    1310                 1315                 1320             


Gly Thr  Asp Arg His Cys Gln  Arg Pro Asp Thr Tyr  Ser Arg Ser 
    1325                 1330                 1335             


Ser Ser  Ala Ser Ser Gln Glu  Glu Lys Ser His Leu  Glu Glu Leu 
    1340                 1345                 1350             


Ala Ala  Gly Gly Ile Pro Ile  Glu Arg Ala Ile Glu  Ser Glu Gly 
    1355                 1360                 1365             


Ala Arg  Pro Ala Val Asp Leu  Ser Phe Gln Pro Ser  Gln Pro Leu 
    1370                 1375                 1380             


Ser Lys  Ser Ser Ser Ser Pro  Glu Leu Gln Thr Leu  Gln Asp Ile 
    1385                 1390                 1395             


Leu Gly  Asp Leu Gly Asp Lys  Ile Asp Ile Gly Arg  Leu Ser Pro 
    1400                 1405                 1410             


Glu Ala  Lys Val Arg Ser Gln  Ser Gly Ile Leu Asp  Gly Glu Ala 
    1415                 1420                 1425             


Ala Thr  Trp Ser Ala Thr Gly  Glu Glu Ser Arg Ile  Thr Val Pro 
    1430                 1435                 1440             


Pro Glu  Gly Pro Leu Pro Ser  Ser Ser Pro Arg Ser  Pro Ser Gly 
    1445                 1450                 1455             


Leu Arg  Pro Arg Gly Tyr Thr  Ile Ser Asp Ser Ala  Pro Ser Arg 
    1460                 1465                 1470             


Arg Gly  Lys Arg Val Glu Arg  Asp Asn Phe Lys Ser  Arg Ala Ala 
    1475                 1480                 1485             


Ala Ser  Ser Ala Glu Lys Val  Pro Gly Ile Asn Pro  Ser Phe Val 
    1490                 1495                 1500             


Phe Leu  Gln Leu Tyr His Ser  Pro Phe Phe Gly Asp  Glu Ser Asn 
    1505                 1510                 1515             


Lys Pro  Ile Leu Leu Pro Asn  Glu Ser Phe Glu Arg  Ser Val Gln 
    1520                 1525                 1530             


Leu Leu  Asp Gln Ile Pro Ser  Tyr Asp Thr His Lys  Ile Ala Val 
    1535                 1540                 1545             


Leu Tyr  Val Gly Glu Gly Gln  Ser Ser Ser Glu Leu  Ala Ile Leu 
    1550                 1555                 1560             


Ser Asn  Glu His Gly Ser Tyr  Arg Tyr Thr Glu Phe  Leu Thr Gly 
    1565                 1570                 1575             


Leu Gly  Arg Leu Ile Glu Leu  Lys Asp Cys Gln Pro  Asp Lys Val 
    1580                 1585                 1590             


Tyr Leu  Gly Gly Leu Asp Val  Cys Gly Glu Asp Gly  Gln Phe Thr 
    1595                 1600                 1605             


Tyr Cys  Trp His Asp Asp Ile  Met Gln Ala Val Phe  His Ile Ala 
    1610                 1615                 1620             


Thr Leu  Met Pro Thr Lys Asp  Val Asp Lys His Arg  Cys Asp Lys 
    1625                 1630                 1635             


Lys Arg  His Leu Gly Asn Asp  Phe Val Ser Ile Ile  Tyr Asn Asp 
    1640                 1645                 1650             


Ser Gly  Glu Asp Phe Lys Leu  Gly Thr Ile Lys Gln  Gly Gln Phe 
    1655                 1660                 1665             


Asn Phe  Val His Val Ile Ile  Thr Pro Leu Asp Tyr  Lys Cys Asn 
    1670                 1675                 1680             


Leu Leu  Thr Leu Gln Cys Arg  Lys Asp Gly Pro Ala  Cys Lys Cys 
    1685                 1690                 1695             


Glu Trp  Trp Arg Gln Pro Gly  Glu Ile Val Val Trp  Ala Leu Pro 
    1700                 1705                 1710             


Val Val  Met Glu Leu Thr Val  Thr Ile Leu Leu Cys  His Leu Gln 
    1715                 1720                 1725             


Met Ala  Ser Gln Val His His  Ser Arg Ser Asn Pro  Thr Asp Ile 
    1730                 1735                 1740             


Tyr Pro  Ser Lys Trp Ile Ala  Arg Leu Arg His Ile  Lys Arg Leu 
    1745                 1750                 1755             


Arg Gln  Arg Ile Arg Glu Glu  Val His Tyr Ser Asn  Pro Ser Leu 
    1760                 1765                 1770             


Pro Leu  Met His Pro Pro Ala  His Thr Lys Ala Pro  Ala Gln Ala 
    1775                 1780                 1785             


Pro Glu  Ala Thr Pro Thr Tyr  Glu Thr Gly Gln Arg  Lys Arg Leu 
    1790                 1795                 1800             


Ile Ser  Ser Val Asp Asp Phe  Thr Glu Phe Val 
    1805                 1810                 


<210>  11
<211>  1809
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  rat TSC2 polypeptide having a S1364E substitution

<400>  11

Met Ala Lys Pro Thr Ser Lys Asp Ser Gly Leu Lys Glu Lys Phe Lys 
1               5                   10                  15      


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


Gly Lys Gln Thr Glu Phe Ile Ile Thr Ala Glu Ile Leu Arg Glu Leu 
        35                  40                  45              


Ser Gly Glu Cys Gly Leu Asn Asn Arg Ile Arg Met Ile Gly Gln Ile 
    50                  55                  60                  


Cys Asp Val Ala Lys Thr Lys Lys Leu Glu Glu His Ala Val Glu Ala 
65                  70                  75                  80  


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


Ala Arg His Ala Val Leu Ala Leu Leu Lys Ala Ile Val Gln Gly Gln 
            100                 105                 110         


Gly Asp Arg Leu Gly Val Leu Arg Ala Leu Phe Phe Lys Val Ile Lys 
        115                 120                 125             


Asp Tyr Pro Ser Asn Glu Asp Leu His Glu Arg Leu Glu Val Phe Lys 
    130                 135                 140                 


Ala Leu Thr Asp Asn Gly Arg His Ile Thr Tyr Leu Glu Glu Glu Leu 
145                 150                 155                 160 


Ala Glu Phe Val Leu Gln Trp Met Asp Val Gly Leu Ser Ser Glu Phe 
                165                 170                 175     


Leu Leu Val Leu Val Asn Leu Val Lys Phe Asn Ser Cys Tyr Leu Asp 
            180                 185                 190         


Glu Tyr Ile Ala Pro Met Val His Met Ile Cys Leu Leu Cys Ile Arg 
        195                 200                 205             


Thr Val Ser Ser Val Asp Ile Glu Val Ser Leu Gln Val Leu Asp Ala 
    210                 215                 220                 


Val Val Cys Tyr Asn Cys Leu Pro Ala Glu Ser Leu Pro Leu Phe Ile 
225                 230                 235                 240 


Ile Thr Leu Cys Arg Thr Val Asn Val Lys Glu Leu Cys Glu Pro Cys 
                245                 250                 255     


Trp Lys Leu Met Arg Asn Leu Leu Gly Thr His Leu Gly His Ser Ala 
            260                 265                 270         


Ile Tyr Asn Met Cys Arg Ile Met Glu Asn Arg Ser Tyr Met Glu Asp 
        275                 280                 285             


Ala Pro Leu Leu Arg Gly Ala Val Phe Phe Val Gly Met Ala Leu Trp 
    290                 295                 300                 


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


Pro Ser Phe Tyr Glu Ala Met Thr Cys Pro Asn Glu Val Val Ser Tyr 
                325                 330                 335     


Glu Ile Val Leu Ser Ile Thr Arg Leu Ile Lys Lys Tyr Arg Lys Glu 
            340                 345                 350         


Leu Gln Ala Val Thr Trp Asp Ile Leu Leu Asp Ile Ile Glu Arg Leu 
        355                 360                 365             


Leu Gln Gln Leu Gln Asn Leu Asp Ser Pro Glu Leu Arg Thr Ile Val 
    370                 375                 380                 


His Asp Leu Leu Thr Thr Val Glu Glu Leu Cys Asp Gln Asn Glu Phe 
385                 390                 395                 400 


His Gly Ser Gln Glu Arg Tyr Tyr Glu Leu Val Glu Ser Tyr Ala Asp 
                405                 410                 415     


Gln Arg Pro Glu Ser Ser Leu Leu Asn Leu Ile Thr Tyr Arg Ala Gln 
            420                 425                 430         


Ser Ile His Pro Ala Lys Asp Gly Trp Ile Gln Asn Leu Gln Leu Leu 
        435                 440                 445             


Met Glu Arg Phe Phe Arg Asn Glu Cys Arg Ser Ala Val Arg Ile Lys 
    450                 455                 460                 


Val Leu Asp Val Leu Ser Phe Val Leu Leu Ile Asn Arg Gln Phe Tyr 
465                 470                 475                 480 


Glu Glu Glu Leu Ile Asn Ser Val Val Ile Ser Gln Leu Ser His Ile 
                485                 490                 495     


Pro Glu Asp Lys Asp His Gln Val Arg Lys Leu Ala Thr Gln Leu Leu 
            500                 505                 510         


Val Asp Leu Ala Glu Gly Cys His Thr His His Phe Asn Ser Leu Leu 
        515                 520                 525             


Asp Ile Ile Glu Lys Val Met Ala Arg Ser Leu Ser Pro Pro Leu Glu 
    530                 535                 540                 


Leu Glu Glu Arg Asp Leu Ala Val Tyr Ser Ala Ser Leu Glu Asp Val 
545                 550                 555                 560 


Lys Thr Ala Val Leu Gly Leu Leu Val Ile Leu Gln Thr Lys Leu Tyr 
                565                 570                 575     


Thr Leu Pro Ala Ser His Ala Thr Arg Val Tyr Glu Thr Leu Ile Ser 
            580                 585                 590         


His Ile Gln Leu His Tyr Lys His Gly Tyr Ser Leu Pro Ile Ala Ser 
        595                 600                 605             


Ser Ile Arg Leu Gln Ala Phe Asp Phe Leu Leu Leu Leu Arg Ala Asp 
    610                 615                 620                 


Ser Leu His Arg Leu Gly Leu Pro Asn Lys Asp Gly Val Val Arg Phe 
625                 630                 635                 640 


Ser Pro Tyr Cys Leu Cys Asp Cys Ala Glu Leu Asp Arg Ala Ser Glu 
                645                 650                 655     


Lys Lys Ala Ser Gly Pro Leu Ser Pro Pro Thr Gly Pro Pro Ser Pro 
            660                 665                 670         


Val Pro Thr Gly Pro Ala Val Arg Leu Gly His Leu Pro Tyr Ser Leu 
        675                 680                 685             


Leu Phe Arg Val Leu Leu Gln Cys Leu Lys Gln Glu Thr Asp Trp Lys 
    690                 695                 700                 


Val Leu Lys Leu Val Leu Ser Lys Leu Pro Glu Ser Leu Arg Tyr Lys 
705                 710                 715                 720 


Val Leu Ile Phe Thr Ser Pro Cys Ser Val Asp Gln Leu Ser Ser Ala 
                725                 730                 735     


Leu Cys Ser Met Leu Ser Ala Pro Lys Thr Leu Glu Arg Leu Arg Gly 
            740                 745                 750         


Thr Pro Glu Gly Phe Ser Arg Thr Asp Leu His Leu Ala Val Val Pro 
        755                 760                 765             


Val Leu Thr Ala Leu Ile Ser Tyr His Asn Tyr Leu Asp Lys Thr Arg 
    770                 775                 780                 


Gln Arg Glu Met Val Tyr Cys Leu Glu Gln Gly Leu Ile Tyr Arg Cys 
785                 790                 795                 800 


Ala Ser Gln Cys Val Val Ala Leu Ala Ile Cys Ser Val Glu Met Pro 
                805                 810                 815     


Asp Ile Ile Ile Lys Ala Leu Pro Val Leu Val Val Lys Leu Thr His 
            820                 825                 830         


Ile Ser Ala Thr Ala Ser Met Ala Ile Pro Leu Leu Glu Phe Leu Ser 
        835                 840                 845             


Thr Leu Ala Arg Leu Pro His Leu Tyr Arg Asn Phe Ala Ala Glu Gln 
    850                 855                 860                 


Tyr Ala Ser Val Phe Ala Ile Ser Leu Pro Tyr Thr Asn Pro Ser Lys 
865                 870                 875                 880 


Phe Asn Gln Tyr Ile Val Cys Leu Ala His His Val Ile Ala Met Trp 
                885                 890                 895     


Phe Ile Arg Cys Arg Leu Pro Phe Arg Lys Asp Phe Val Pro Tyr Ile 
            900                 905                 910         


Thr Lys Gly Leu Arg Ser Asn Val Leu Leu Ser Phe Asp Asp Thr Pro 
        915                 920                 925             


Glu Lys Asp Lys Phe Arg Ala Arg Ser Thr Ser Leu Asn Glu Arg Pro 
    930                 935                 940                 


Lys Ser Leu Arg Ile Ala Arg Ala Pro Lys Gln Gly Leu Asn Asn Ser 
945                 950                 955                 960 


Pro Pro Val Lys Glu Phe Lys Glu Ser Cys Ala Ala Glu Ala Phe Arg 
                965                 970                 975     


Cys Arg Ser Ile Ser Val Ser Glu His Val Val Arg Ser Arg Ile Gln 
            980                 985                 990         


Thr Ser Leu Thr Ser Ala Ser Leu  Gly Ser Ala Asp Glu  Asn Ser Met 
        995                 1000                 1005             


Ala Gln  Ala Asp Asp Asn Leu  Lys Asn Leu His Leu  Glu Leu Thr 
    1010                 1015                 1020             


Glu Thr  Cys Leu Asp Met Met  Ala Arg Tyr Val Phe  Ser Asn Phe 
    1025                 1030                 1035             


Thr Ala  Val Pro Lys Arg Ser  Pro Val Gly Glu Phe  Leu Leu Ala 
    1040                 1045                 1050             


Gly Gly  Arg Thr Lys Thr Trp  Leu Val Gly Asn Lys  Leu Val Thr 
    1055                 1060                 1065             


Val Thr  Thr Ser Val Gly Thr  Gly Thr Arg Ser Leu  Leu Gly Leu 
    1070                 1075                 1080             


Asp Ser  Gly Asp Leu Gln Gly  Gly Ser Ala Ser Ser  Ser Asp Pro 
    1085                 1090                 1095             


Gly Thr  His Val Arg Gln Thr  Lys Glu Ala Pro Ala  Lys Leu Glu 
    1100                 1105                 1110             


Ser Gln  Ala Gly Gln Gln Val  Ser Arg Gly Ala Arg  Asp Arg Val 
    1115                 1120                 1125             


Arg Ser  Met Ser Gly Gly His  Gly Leu Arg Val Gly  Val Leu Asp 
    1130                 1135                 1140             


Thr Ser  Ala Pro Tyr Thr Pro  Gly Gly Pro Ala Ser  Leu Gly Ala 
    1145                 1150                 1155             


Gln Ala  Ala Pro Ala Ala Arg  Pro Glu Lys Pro Cys  Ala Gly Ala 
    1160                 1165                 1170             


Gln Leu  Pro Ala Ala Glu Lys  Ala Asn Leu Ala Ala  Tyr Val Pro 
    1175                 1180                 1185             


Leu Leu  Thr Gln Gly Trp Ala  Glu Ile Leu Val Arg  Arg Pro Thr 
    1190                 1195                 1200             


Gly Asn  Thr Ser Trp Leu Met  Ser Leu Glu Asn Pro  Leu Ser Pro 
    1205                 1210                 1215             


Phe Ser  Ser Asp Ile Asn Asn  Met Pro Leu Gln Glu  Leu Ser Asn 
    1220                 1225                 1230             


Ala Leu  Met Ala Ala Glu Arg  Phe Lys Glu His Arg  Asp Thr Ala 
    1235                 1240                 1245             


Leu Tyr  Lys Ser Leu Ser Val  Pro Ala Ala Gly Thr  Ala Lys Pro 
    1250                 1255                 1260             


Pro Thr  Leu Pro Arg Ser Asn  Thr Val Ala Ser Phe  Ser Ser Leu 
    1265                 1270                 1275             


Tyr Gln  Pro Ser Cys Gln Gly  Gln Leu His Arg Ser  Val Ser Trp 
    1280                 1285                 1290             


Ala Asp  Ser Ala Val Val Leu  Glu Glu Gly Ser Pro  Gly Glu Ala 
    1295                 1300                 1305             


His Val  Pro Val Glu Pro Pro  Glu Leu Glu Asp Phe  Glu Ala Ala 
    1310                 1315                 1320             


Leu Gly  Thr Asp Arg His Cys  Gln Arg Pro Asp Ala  Tyr Ser Arg 
    1325                 1330                 1335             


Ser Ser  Ser Ala Ser Ser Gln  Glu Glu Lys Ser His  Leu Glu Glu 
    1340                 1345                 1350             


Leu Ala  Ala Gly Gly Ile Pro  Ile Glu Arg Ala Ile  Glu Ser Glu 
    1355                 1360                 1365             


Gly Ala  Arg Pro Thr Val Asp  Leu Ser Phe Gln Pro  Ser Gln Pro 
    1370                 1375                 1380             


Leu Ser  Lys Ser Ser Ser Ser  Pro Glu Leu Gln Thr  Leu Gln Asp 
    1385                 1390                 1395             


Ile Leu  Gly Asp Leu Gly Asp  Lys Thr Asp Ile Gly  Arg Leu Ser 
    1400                 1405                 1410             


Pro Glu  Ala Lys Val Arg Ser  Gln Ser Gly Ile Leu  Asp Gly Glu 
    1415                 1420                 1425             


Ala Ala  Thr Trp Ser Ala Pro  Gly Glu Glu Ser Arg  Ile Thr Val 
    1430                 1435                 1440             


Pro Pro  Glu Gly Pro Leu Pro  Ser Ser Ser Pro Arg  Ser Pro Ser 
    1445                 1450                 1455             


Gly Leu  Arg Pro Arg Gly Tyr  Thr Ile Ser Asp Ser  Ala Pro Ser 
    1460                 1465                 1470             


Arg Arg  Gly Lys Arg Val Glu  Arg Asp Asn Phe Lys  Ser Arg Thr 
    1475                 1480                 1485             


Ala Ala  Ser Ser Ala Glu Lys  Val Pro Gly Ile Asn  Pro Ser Phe 
    1490                 1495                 1500             


Val Phe  Leu Gln Leu Tyr His  Ser Pro Phe Cys Gly  Asp Glu Ser 
    1505                 1510                 1515             


Asn Lys  Pro Ile Leu Leu Pro  Asn Glu Ser Phe Glu  Arg Ser Val 
    1520                 1525                 1530             


Gln Leu  Leu Asp Gln Ile Pro  Ser Tyr Asp Thr His  Lys Ile Ala 
    1535                 1540                 1545             


Val Leu  Tyr Val Gly Glu Gly  Gln Ser Ser Ser Glu  Leu Ala Ile 
    1550                 1555                 1560             


Leu Ser  Asn Glu His Gly Ser  Tyr Arg Tyr Thr Glu  Phe Leu Thr 
    1565                 1570                 1575             


Gly Leu  Gly Arg Leu Ile Glu  Leu Lys Asp Cys Gln  Pro Asp Lys 
    1580                 1585                 1590             


Val Tyr  Leu Gly Gly Leu Asp  Val Cys Gly Glu Asp  Gly Gln Phe 
    1595                 1600                 1605             


Thr Tyr  Cys Trp His Asp Asp  Ile Met Gln Ala Val  Phe His Ile 
    1610                 1615                 1620             


Ala Thr  Leu Met Pro Thr Lys  Asp Val Asp Lys His  Arg Cys Asp 
    1625                 1630                 1635             


Lys Lys  Arg His Leu Gly Asn  Asp Phe Val Ser Ile  Ile Tyr Asn 
    1640                 1645                 1650             


Asp Ser  Gly Glu Asp Phe Lys  Leu Gly Thr Ile Lys  Gly Gln Phe 
    1655                 1660                 1665             


Asn Phe  Val His Val Ile Ile  Thr Pro Leu Asp Tyr  Lys Cys Asn 
    1670                 1675                 1680             


Leu Leu  Thr Leu Gln Cys Arg  Lys Asp Met Glu Gly  Leu Val Asp 
    1685                 1690                 1695             


Thr Ser  Val Ala Lys Ile Val  Ser Asp Arg Asn Leu  Ser Phe Val 
    1700                 1705                 1710             


Ala Arg  Gln Met Ala Leu His  Ala Asn Met Ala Ser  Gln Val His 
    1715                 1720                 1725             


His Arg  Arg Ser Asn Pro Thr  Asp Ile Tyr Pro Ser  Lys Trp Ile 
    1730                 1735                 1740             


Ala Arg  Leu Arg His Ile Lys  Arg Leu Arg Gln Arg  Ile Arg Glu 
    1745                 1750                 1755             


Glu Val  His Tyr Ser Asn Pro  Ser Leu Pro Leu Met  His Pro Pro 
    1760                 1765                 1770             


Ala His  Thr Lys Val Pro Ala  Gln Ala Pro Thr Glu  Ala Thr Pro 
    1775                 1780                 1785             


Thr Tyr  Glu Thr Gly Gln Arg  Lys Arg Leu Ile Ser  Ser Val Asp 
    1790                 1795                 1800             


Asp Phe  Thr Glu Phe Val 
    1805                 


