                         SEQUENCE LISTING

<110>  Revolution Medicines, Inc.
 
<120>  C40-, C28-, and C-32-Linked Rapamycin Analogs as mTOR Inhibitors

<130>  REME-008/01WO 323913-2136

<150>  US 62/836,036
<151>  2019-04-18

<150>  US 62/752,874
<151>  2018-10-30

<150>  US 62/665,435
<151>  2018-05-01

<160>  5     

<170>  PatentIn version 3.5

<210>  1
<211>  2549
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Leu Gly Thr Gly Pro Ala Ala Ala Thr Thr Ala Ala Thr Thr Ser 
1               5                   10                  15      


Ser Asn Val Ser Val Leu Gln Gln Phe Ala Ser Gly Leu Lys Ser Arg 
            20                  25                  30          


Asn Glu Glu Thr Arg Ala Lys Ala Ala Lys Glu Leu Gln His Tyr Val 
        35                  40                  45              


Thr Met Glu Leu Arg Glu Met Ser Gln Glu Glu Ser Thr Arg Phe Tyr 
    50                  55                  60                  


Asp Gln Leu Asn His His Ile Phe Glu Leu Val Ser Ser Ser Asp Ala 
65                  70                  75                  80  


Asn Glu Arg Lys Gly Gly Ile Leu Ala Ile Ala Ser Leu Ile Gly Val 
                85                  90                  95      


Glu Gly Gly Asn Ala Thr Arg Ile Gly Arg Phe Ala Asn Tyr Leu Arg 
            100                 105                 110         


Asn Leu Leu Pro Ser Asn Asp Pro Val Val Met Glu Met Ala Ser Lys 
        115                 120                 125             


Ala Ile Gly Arg Leu Ala Met Ala Gly Asp Thr Phe Thr Ala Glu Tyr 
    130                 135                 140                 


Val Glu Phe Glu Val Lys Arg Ala Leu Glu Trp Leu Gly Ala Asp Arg 
145                 150                 155                 160 


Asn Glu Gly Arg Arg His Ala Ala Val Leu Val Leu Arg Glu Leu Ala 
                165                 170                 175     


Ile Ser Val Pro Thr Phe Phe Phe Gln Gln Val Gln Pro Phe Phe Asp 
            180                 185                 190         


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


Ala Val Ala Ala Leu Arg Ala Cys Leu Ile Leu Thr Thr Gln Arg Glu 
    210                 215                 220                 


Pro Lys Glu Met Gln Lys Pro Gln Trp Tyr Arg His Thr Phe Glu Glu 
225                 230                 235                 240 


Ala Glu Lys Gly Phe Asp Glu Thr Leu Ala Lys Glu Lys Gly Met Asn 
                245                 250                 255     


Arg Asp Asp Arg Ile His Gly Ala Leu Leu Ile Leu Asn Glu Leu Val 
            260                 265                 270         


Arg Ile Ser Ser Met Glu Gly Glu Arg Leu Arg Glu Glu Met Glu Glu 
        275                 280                 285             


Ile Thr Gln Gln Gln Leu Val His Asp Lys Tyr Cys Lys Asp Leu Met 
    290                 295                 300                 


Gly Phe Gly Thr Lys Pro Arg His Ile Thr Pro Phe Thr Ser Phe Gln 
305                 310                 315                 320 


Ala Val Gln Pro Gln Gln Ser Asn Ala Leu Val Gly Leu Leu Gly Tyr 
                325                 330                 335     


Ser Ser His Gln Gly Leu Met Gly Phe Gly Thr Ser Pro Ser Pro Ala 
            340                 345                 350         


Lys Ser Thr Leu Val Glu Ser Arg Cys Cys Arg Asp Leu Met Glu Glu 
        355                 360                 365             


Lys Phe Asp Gln Val Cys Gln Trp Val Leu Lys Cys Arg Asn Ser Lys 
    370                 375                 380                 


Asn Ser Leu Ile Gln Met Thr Ile Leu Asn Leu Leu Pro Arg Leu Ala 
385                 390                 395                 400 


Ala Phe Arg Pro Ser Ala Phe Thr Asp Thr Gln Tyr Leu Gln Asp Thr 
                405                 410                 415     


Met Asn His Val Leu Ser Cys Val Lys Lys Glu Lys Glu Arg Thr Ala 
            420                 425                 430         


Ala Phe Gln Ala Leu Gly Leu Leu Ser Val Ala Val Arg Ser Glu Phe 
        435                 440                 445             


Lys Val Tyr Leu Pro Arg Val Leu Asp Ile Ile Arg Ala Ala Leu Pro 
    450                 455                 460                 


Pro Lys Asp Phe Ala His Lys Arg Gln Lys Ala Met Gln Val Asp Ala 
465                 470                 475                 480 


Thr Val Phe Thr Cys Ile Ser Met Leu Ala Arg Ala Met Gly Pro Gly 
                485                 490                 495     


Ile Gln Gln Asp Ile Lys Glu Leu Leu Glu Pro Met Leu Ala Val Gly 
            500                 505                 510         


Leu Ser Pro Ala Leu Thr Ala Val Leu Tyr Asp Leu Ser Arg Gln Ile 
        515                 520                 525             


Pro Gln Leu Lys Lys Asp Ile Gln Asp Gly Leu Leu Lys Met Leu Ser 
    530                 535                 540                 


Leu Val Leu Met His Lys Pro Leu Arg His Pro Gly Met Pro Lys Gly 
545                 550                 555                 560 


Leu Ala His Gln Leu Ala Ser Pro Gly Leu Thr Thr Leu Pro Glu Ala 
                565                 570                 575     


Ser Asp Val Gly Ser Ile Thr Leu Ala Leu Arg Thr Leu Gly Ser Phe 
            580                 585                 590         


Glu Phe Glu Gly His Ser Leu Thr Gln Phe Val Arg His Cys Ala Asp 
        595                 600                 605             


His Phe Leu Asn Ser Glu His Lys Glu Ile Arg Met Glu Ala Ala Arg 
    610                 615                 620                 


Thr Cys Ser Arg Leu Leu Thr Pro Ser Ile His Leu Ile Ser Gly His 
625                 630                 635                 640 


Ala His Val Val Ser Gln Thr Ala Val Gln Val Val Ala Asp Val Leu 
                645                 650                 655     


Ser Lys Leu Leu Val Val Gly Ile Thr Asp Pro Asp Pro Asp Ile Arg 
            660                 665                 670         


Tyr Cys Val Leu Ala Ser Leu Asp Glu Arg Phe Asp Ala His Leu Ala 
        675                 680                 685             


Gln Ala Glu Asn Leu Gln Ala Leu Phe Val Ala Leu Asn Asp Gln Val 
    690                 695                 700                 


Phe Glu Ile Arg Glu Leu Ala Ile Cys Thr Val Gly Arg Leu Ser Ser 
705                 710                 715                 720 


Met Asn Pro Ala Phe Val Met Pro Phe Leu Arg Lys Met Leu Ile Gln 
                725                 730                 735     


Ile Leu Thr Glu Leu Glu His Ser Gly Ile Gly Arg Ile Lys Glu Gln 
            740                 745                 750         


Ser Ala Arg Met Leu Gly His Leu Val Ser Asn Ala Pro Arg Leu Ile 
        755                 760                 765             


Arg Pro Tyr Met Glu Pro Ile Leu Lys Ala Leu Ile Leu Lys Leu Lys 
    770                 775                 780                 


Asp Pro Asp Pro Asp Pro Asn Pro Gly Val Ile Asn Asn Val Leu Ala 
785                 790                 795                 800 


Thr Ile Gly Glu Leu Ala Gln Val Ser Gly Leu Glu Met Arg Lys Trp 
                805                 810                 815     


Val Asp Glu Leu Phe Ile Ile Ile Met Asp Met Leu Gln Asp Ser Ser 
            820                 825                 830         


Leu Leu Ala Lys Arg Gln Val Ala Leu Trp Thr Leu Gly Gln Leu Val 
        835                 840                 845             


Ala Ser Thr Gly Tyr Val Val Glu Pro Tyr Arg Lys Tyr Pro Thr Leu 
    850                 855                 860                 


Leu Glu Val Leu Leu Asn Phe Leu Lys Thr Glu Gln Asn Gln Gly Thr 
865                 870                 875                 880 


Arg Arg Glu Ala Ile Arg Val Leu Gly Leu Leu Gly Ala Leu Asp Pro 
                885                 890                 895     


Tyr Lys His Lys Val Asn Ile Gly Met Ile Asp Gln Ser Arg Asp Ala 
            900                 905                 910         


Ser Ala Val Ser Leu Ser Glu Ser Lys Ser Ser Gln Asp Ser Ser Asp 
        915                 920                 925             


Tyr Ser Thr Ser Glu Met Leu Val Asn Met Gly Asn Leu Pro Leu Asp 
    930                 935                 940                 


Glu Phe Tyr Pro Ala Val Ser Met Val Ala Leu Met Arg Ile Phe Arg 
945                 950                 955                 960 


Asp Gln Ser Leu Ser His His His Thr Met Val Val Gln Ala Ile Thr 
                965                 970                 975     


Phe Ile Phe Lys Ser Leu Gly Leu Lys Cys Val Gln Phe Leu Pro Gln 
            980                 985                 990         


Val Met Pro Thr Phe Leu Asn Val  Ile Arg Val Cys Asp  Gly Ala Ile 
        995                 1000                 1005             


Arg Glu  Phe Leu Phe Gln Gln  Leu Gly Met Leu Val  Ser Phe Val 
    1010                 1015                 1020             


Lys Ser  His Ile Arg Pro Tyr  Met Asp Glu Ile Val  Thr Leu Met 
    1025                 1030                 1035             


Arg Glu  Phe Trp Val Met Asn  Thr Ser Ile Gln Ser  Thr Ile Ile 
    1040                 1045                 1050             


Leu Leu  Ile Glu Gln Ile Val  Val Ala Leu Gly Gly  Glu Phe Lys 
    1055                 1060                 1065             


Leu Tyr  Leu Pro Gln Leu Ile  Pro His Met Leu Arg  Val Phe Met 
    1070                 1075                 1080             


His Asp  Asn Ser Pro Gly Arg  Ile Val Ser Ile Lys  Leu Leu Ala 
    1085                 1090                 1095             


Ala Ile  Gln Leu Phe Gly Ala  Asn Leu Asp Asp Tyr  Leu His Leu 
    1100                 1105                 1110             


Leu Leu  Pro Pro Ile Val Lys  Leu Phe Asp Ala Pro  Glu Ala Pro 
    1115                 1120                 1125             


Leu Pro  Ser Arg Lys Ala Ala  Leu Glu Thr Val Asp  Arg Leu Thr 
    1130                 1135                 1140             


Glu Ser  Leu Asp Phe Thr Asp  Tyr Ala Ser Arg Ile  Ile His Pro 
    1145                 1150                 1155             


Ile Val  Arg Thr Leu Asp Gln  Ser Pro Glu Leu Arg  Ser Thr Ala 
    1160                 1165                 1170             


Met Asp  Thr Leu Ser Ser Leu  Val Phe Gln Leu Gly  Lys Lys Tyr 
    1175                 1180                 1185             


Gln Ile  Phe Ile Pro Met Val  Asn Lys Val Leu Val  Arg His Arg 
    1190                 1195                 1200             


Ile Asn  His Gln Arg Tyr Asp  Val Leu Ile Cys Arg  Ile Val Lys 
    1205                 1210                 1215             


Gly Tyr  Thr Leu Ala Asp Glu  Glu Glu Asp Pro Leu  Ile Tyr Gln 
    1220                 1225                 1230             


His Arg  Met Leu Arg Ser Gly  Gln Gly Asp Ala Leu  Ala Ser Gly 
    1235                 1240                 1245             


Pro Val  Glu Thr Gly Pro Met  Lys Lys Leu His Val  Ser Thr Ile 
    1250                 1255                 1260             


Asn Leu  Gln Lys Ala Trp Gly  Ala Ala Arg Arg Val  Ser Lys Asp 
    1265                 1270                 1275             


Asp Trp  Leu Glu Trp Leu Arg  Arg Leu Ser Leu Glu  Leu Leu Lys 
    1280                 1285                 1290             


Asp Ser  Ser Ser Pro Ser Leu  Arg Ser Cys Trp Ala  Leu Ala Gln 
    1295                 1300                 1305             


Ala Tyr  Asn Pro Met Ala Arg  Asp Leu Phe Asn Ala  Ala Phe Val 
    1310                 1315                 1320             


Ser Cys  Trp Ser Glu Leu Asn  Glu Asp Gln Gln Asp  Glu Leu Ile 
    1325                 1330                 1335             


Arg Ser  Ile Glu Leu Ala Leu  Thr Ser Gln Asp Ile  Ala Glu Val 
    1340                 1345                 1350             


Thr Gln  Thr Leu Leu Asn Leu  Ala Glu Phe Met Glu  His Ser Asp 
    1355                 1360                 1365             


Lys Gly  Pro Leu Pro Leu Arg  Asp Asp Asn Gly Ile  Val Leu Leu 
    1370                 1375                 1380             


Gly Glu  Arg Ala Ala Lys Cys  Arg Ala Tyr Ala Lys  Ala Leu His 
    1385                 1390                 1395             


Tyr Lys  Glu Leu Glu Phe Gln  Lys Gly Pro Thr Pro  Ala Ile Leu 
    1400                 1405                 1410             


Glu Ser  Leu Ile Ser Ile Asn  Asn Lys Leu Gln Gln  Pro Glu Ala 
    1415                 1420                 1425             


Ala Ala  Gly Val Leu Glu Tyr  Ala Met Lys His Phe  Gly Glu Leu 
    1430                 1435                 1440             


Glu Ile  Gln Ala Thr Trp Tyr  Glu Lys Leu His Glu  Trp Glu Asp 
    1445                 1450                 1455             


Ala Leu  Val Ala Tyr Asp Lys  Lys Met Asp Thr Asn  Lys Asp Asp 
    1460                 1465                 1470             


Pro Glu  Leu Met Leu Gly Arg  Met Arg Cys Leu Glu  Ala Leu Gly 
    1475                 1480                 1485             


Glu Trp  Gly Gln Leu His Gln  Gln Cys Cys Glu Lys  Trp Thr Leu 
    1490                 1495                 1500             


Val Asn  Asp Glu Thr Gln Ala  Lys Met Ala Arg Met  Ala Ala Ala 
    1505                 1510                 1515             


Ala Ala  Trp Gly Leu Gly Gln  Trp Asp Ser Met Glu  Glu Tyr Thr 
    1520                 1525                 1530             


Cys Met  Ile Pro Arg Asp Thr  His Asp Gly Ala Phe  Tyr Arg Ala 
    1535                 1540                 1545             


Val Leu  Ala Leu His Gln Asp  Leu Phe Ser Leu Ala  Gln Gln Cys 
    1550                 1555                 1560             


Ile Asp  Lys Ala Arg Asp Leu  Leu Asp Ala Glu Leu  Thr Ala Met 
    1565                 1570                 1575             


Ala Gly  Glu Ser Tyr Ser Arg  Ala Tyr Gly Ala Met  Val Ser Cys 
    1580                 1585                 1590             


His Met  Leu Ser Glu Leu Glu  Glu Val Ile Gln Tyr  Lys Leu Val 
    1595                 1600                 1605             


Pro Glu  Arg Arg Glu Ile Ile  Arg Gln Ile Trp Trp  Glu Arg Leu 
    1610                 1615                 1620             


Gln Gly  Cys Gln Arg Ile Val  Glu Asp Trp Gln Lys  Ile Leu Met 
    1625                 1630                 1635             


Val Arg  Ser Leu Val Val Ser  Pro His Glu Asp Met  Arg Thr Trp 
    1640                 1645                 1650             


Leu Lys  Tyr Ala Ser Leu Cys  Gly Lys Ser Gly Arg  Leu Ala Leu 
    1655                 1660                 1665             


Ala His  Lys Thr Leu Val Leu  Leu Leu Gly Val Asp  Pro Ser Arg 
    1670                 1675                 1680             


Gln Leu  Asp His Pro Leu Pro  Thr Val His Pro Gln  Val Thr Tyr 
    1685                 1690                 1695             


Ala Tyr  Met Lys Asn Met Trp  Lys Ser Ala Arg Lys  Ile Asp Ala 
    1700                 1705                 1710             


Phe Gln  His Met Gln His Phe  Val Gln Thr Met Gln  Gln Gln Ala 
    1715                 1720                 1725             


Gln His  Ala Ile Ala Thr Glu  Asp Gln Gln His Lys  Gln Glu Leu 
    1730                 1735                 1740             


His Lys  Leu Met Ala Arg Cys  Phe Leu Lys Leu Gly  Glu Trp Gln 
    1745                 1750                 1755             


Leu Asn  Leu Gln Gly Ile Asn  Glu Ser Thr Ile Pro  Lys Val Leu 
    1760                 1765                 1770             


Gln Tyr  Tyr Ser Ala Ala Thr  Glu His Asp Arg Ser  Trp Tyr Lys 
    1775                 1780                 1785             


Ala Trp  His Ala Trp Ala Val  Met Asn Phe Glu Ala  Val Leu His 
    1790                 1795                 1800             


Tyr Lys  His Gln Asn Gln Ala  Arg Asp Glu Lys Lys  Lys Leu Arg 
    1805                 1810                 1815             


His Ala  Ser Gly Ala Asn Ile  Thr Asn Ala Thr Thr  Ala Ala Thr 
    1820                 1825                 1830             


Thr Ala  Ala Thr Ala Thr Thr  Thr Ala Ser Thr Glu  Gly Ser Asn 
    1835                 1840                 1845             


Ser Glu  Ser Glu Ala Glu Ser  Thr Glu Asn Ser Pro  Thr Pro Ser 
    1850                 1855                 1860             


Pro Leu  Gln Lys Lys Val Thr  Glu Asp Leu Ser Lys  Thr Leu Leu 
    1865                 1870                 1875             


Met Tyr  Thr Val Pro Ala Val  Gln Gly Phe Phe Arg  Ser Ile Ser 
    1880                 1885                 1890             


Leu Ser  Arg Gly Asn Asn Leu  Gln Asp Thr Leu Arg  Val Leu Thr 
    1895                 1900                 1905             


Leu Trp  Phe Asp Tyr Gly His  Trp Pro Asp Val Asn  Glu Ala Leu 
    1910                 1915                 1920             


Val Glu  Gly Val Lys Ala Ile  Gln Ile Asp Thr Trp  Leu Gln Val 
    1925                 1930                 1935             


Ile Pro  Gln Leu Ile Ala Arg  Ile Asp Thr Pro Arg  Pro Leu Val 
    1940                 1945                 1950             


Gly Arg  Leu Ile His Gln Leu  Leu Thr Asp Ile Gly  Arg Tyr His 
    1955                 1960                 1965             


Pro Gln  Ala Leu Ile Tyr Pro  Leu Thr Val Ala Ser  Lys Ser Thr 
    1970                 1975                 1980             


Thr Thr  Ala Arg His Asn Ala  Ala Asn Lys Ile Leu  Lys Asn Met 
    1985                 1990                 1995             


Cys Glu  His Ser Asn Thr Leu  Val Gln Gln Ala Met  Met Val Ser 
    2000                 2005                 2010             


Glu Glu  Leu Ile Arg Val Ala  Ile Leu Trp His Glu  Met Trp His 
    2015                 2020                 2025             


Glu Gly  Leu Glu Glu Ala Ser  Arg Leu Tyr Phe Gly  Glu Arg Asn 
    2030                 2035                 2040             


Val Lys  Gly Met Phe Glu Val  Leu Glu Pro Leu His  Ala Met Met 
    2045                 2050                 2055             


Glu Arg  Gly Pro Gln Thr Leu  Lys Glu Thr Ser Phe  Asn Gln Ala 
    2060                 2065                 2070             


Tyr Gly  Arg Asp Leu Met Glu  Ala Gln Glu Trp Cys  Arg Lys Tyr 
    2075                 2080                 2085             


Met Lys  Ser Gly Asn Val Lys  Asp Leu Thr Gln Ala  Trp Asp Leu 
    2090                 2095                 2100             


Tyr Tyr  His Val Phe Arg Arg  Ile Ser Lys Gln Leu  Pro Gln Leu 
    2105                 2110                 2115             


Thr Ser  Leu Glu Leu Gln Tyr  Val Ser Pro Lys Leu  Leu Met Cys 
    2120                 2125                 2130             


Arg Asp  Leu Glu Leu Ala Val  Pro Gly Thr Tyr Asp  Pro Asn Gln 
    2135                 2140                 2145             


Pro Ile  Ile Arg Ile Gln Ser  Ile Ala Pro Ser Leu  Gln Val Ile 
    2150                 2155                 2160             


Thr Ser  Lys Gln Arg Pro Arg  Lys Leu Thr Leu Met  Gly Ser Asn 
    2165                 2170                 2175             


Gly His  Glu Phe Val Phe Leu  Leu Lys Gly His Glu  Asp Leu Arg 
    2180                 2185                 2190             


Gln Asp  Glu Arg Val Met Gln  Leu Phe Gly Leu Val  Asn Thr Leu 
    2195                 2200                 2205             


Leu Ala  Asn Asp Pro Thr Ser  Leu Arg Lys Asn Leu  Ser Ile Gln 
    2210                 2215                 2220             


Arg Tyr  Ala Val Ile Pro Leu  Ser Thr Asn Ser Gly  Leu Ile Gly 
    2225                 2230                 2235             


Trp Val  Pro His Cys Asp Thr  Leu His Ala Leu Ile  Arg Asp Tyr 
    2240                 2245                 2250             


Arg Glu  Lys Lys Lys Ile Leu  Leu Asn Ile Glu His  Arg Ile Met 
    2255                 2260                 2265             


Leu Arg  Met Ala Pro Asp Tyr  Asp His Leu Thr Leu  Met Gln Lys 
    2270                 2275                 2280             


Val Glu  Val Phe Glu His Ala  Val Asn Asn Thr Ala  Gly Asp Asp 
    2285                 2290                 2295             


Leu Ala  Lys Leu Leu Trp Leu  Lys Ser Pro Ser Ser  Glu Val Trp 
    2300                 2305                 2310             


Phe Asp  Arg Arg Thr Asn Tyr  Thr Arg Ser Leu Ala  Val Met Ser 
    2315                 2320                 2325             


Met Val  Gly Tyr Ile Leu Gly  Leu Gly Asp Arg His  Pro Ser Asn 
    2330                 2335                 2340             


Leu Met  Leu Asp Arg Leu Ser  Gly Lys Ile Leu His  Ile Asp Phe 
    2345                 2350                 2355             


Gly Asp  Cys Phe Glu Val Ala  Met Thr Arg Glu Lys  Phe Pro Glu 
    2360                 2365                 2370             


Lys Ile  Pro Phe Arg Leu Thr  Arg Met Leu Thr Asn  Ala Met Glu 
    2375                 2380                 2385             


Val Thr  Gly Leu Asp Gly Asn  Tyr Arg Ile Thr Cys  His Thr Val 
    2390                 2395                 2400             


Met Glu  Val Leu Arg Glu His  Lys Asp Ser Val Met  Ala Val Leu 
    2405                 2410                 2415             


Glu Ala  Phe Val Tyr Asp Pro  Leu Leu Asn Trp Arg  Leu Met Asp 
    2420                 2425                 2430             


Thr Asn  Thr Lys Gly Asn Lys  Arg Ser Arg Thr Arg  Thr Asp Ser 
    2435                 2440                 2445             


Tyr Ser  Ala Gly Gln Ser Val  Glu Ile Leu Asp Gly  Val Glu Leu 
    2450                 2455                 2460             


Gly Glu  Pro Ala His Lys Lys  Thr Gly Thr Thr Val  Pro Glu Ser 
    2465                 2470                 2475             


Ile His  Ser Phe Ile Gly Asp  Gly Leu Val Lys Pro  Glu Ala Leu 
    2480                 2485                 2490             


Asn Lys  Lys Ala Ile Gln Ile  Ile Asn Arg Val Arg  Asp Lys Leu 
    2495                 2500                 2505             


Thr Gly  Arg Asp Phe Ser His  Asp Asp Thr Leu Asp  Val Pro Thr 
    2510                 2515                 2520             


Gln Val  Glu Leu Leu Ile Lys  Gln Ala Thr Ser His  Glu Asn Leu 
    2525                 2530                 2535             


Cys Gln  Cys Tyr Ile Gly Trp  Cys Pro Phe Trp 
    2540                 2545                 


<210>  2
<211>  8733
<212>  DNA
<213>  Homo sapiens

<400>  2
gctcccggct tagaggacag cggggaaggc gggcggtggg gcagggggcc tgaagcggcg       60

gtaccggtgc tggcggcggc agctgaggcc ttggccgaag ccgcgcgaac ctcagggcaa      120

gatgcttgga accggacctg ccgccgccac caccgctgcc accacatcta gcaatgtgag      180

cgtcctgcag cagtttgcca gtggcctaaa gagccggaat gaggaaacca gggccaaagc      240

cgccaaggag ctccagcact atgtcaccat ggaactccga gagatgagtc aagaggagtc      300

tactcgcttc tatgaccaac tgaaccatca catttttgaa ttggtttcca gctcagatgc      360

caatgagagg aaaggtggca tcttggccat agctagcctc ataggagtgg aaggtgggaa      420

tgccacccga attggcagat ttgccaacta tcttcggaac ctcctcccct ccaatgaccc      480

agttgtcatg gaaatggcat ccaaggccat tggccgtctt gccatggcag gggacacttt      540

taccgctgag tacgtggaat ttgaggtgaa gcgagccctg gaatggctgg gtgctgaccg      600

caatgagggc cggagacatg cagctgtcct ggttctccgt gagctggcca tcagcgtccc      660

taccttcttc ttccagcaag tgcaaccctt ctttgacaac atttttgtgg ccgtgtggga      720

ccccaaacag gccatccgtg agggagctgt agccgccctt cgtgcctgtc tgattctcac      780

aacccagcgt gagccgaagg agatgcagaa gcctcagtgg tacaggcaca catttgaaga      840

agcagagaag ggatttgatg agaccttggc caaagagaag ggcatgaatc gggatgatcg      900

gatccatgga gccttgttga tccttaacga gctggtccga atcagcagca tggagggaga      960

gcgtctgaga gaagaaatgg aagaaatcac acagcagcag ctggtacacg acaagtactg     1020

caaagatctc atgggcttcg gaacaaaacc tcgtcacatt acccccttca ccagtttcca     1080

ggctgtacag ccccagcagt caaatgcctt ggtggggctg ctggggtaca gctctcacca     1140

aggcctcatg ggatttggga cctcccccag tccagctaag tccaccctgg tggagagccg     1200

gtgttgcaga gacttgatgg aggagaaatt tgatcaggtg tgccagtggg tgctgaaatg     1260

caggaatagc aagaactcgc tgatccaaat gacaatcctt aatttgttgc cccgcttggc     1320

tgcattccga ccttctgcct tcacagatac ccagtatctc caagatacca tgaaccatgt     1380

cctaagctgt gtcaagaagg agaaggaacg tacagcggcc ttccaagccc tggggctact     1440

ttctgtggct gtgaggtctg agtttaaggt ctatttgcct cgcgtgctgg acatcatccg     1500

agcggccctg cccccaaagg acttcgccca taagaggcag aaggcaatgc aggtggatgc     1560

cacagtcttc acttgcatca gcatgctggc tcgagcaatg gggccaggca tccagcagga     1620

tatcaaggag ctgctggagc ccatgctggc agtgggacta agccctgccc tcactgcagt     1680

gctctacgac ctgagccgtc agattccaca gctaaagaag gacattcaag atgggctact     1740

gaaaatgctg tccctggtcc ttatgcacaa accccttcgc cacccaggca tgcccaaggg     1800

cctggcccat cagctggcct ctcctggcct cacgaccctc cctgaggcca gcgatgtggg     1860

cagcatcact cttgccctcc gaacgcttgg cagctttgaa tttgaaggcc actctctgac     1920

ccaatttgtt cgccactgtg cggatcattt cctgaacagt gagcacaagg agatccgcat     1980

ggaggctgcc cgcacctgct cccgcctgct cacaccctcc atccacctca tcagtggcca     2040

tgctcatgtg gttagccaga ccgcagtgca agtggtggca gatgtgctta gcaaactgct     2100

cgtagttggg ataacagatc ctgaccctga cattcgctac tgtgtcttgg cgtccctgga     2160

cgagcgcttt gatgcacacc tggcccaggc ggagaacttg caggccttgt ttgtggctct     2220

gaatgaccag gtgtttgaga tccgggagct ggccatctgc actgtgggcc gactcagtag     2280

catgaaccct gcctttgtca tgcctttcct gcgcaagatg ctcatccaga ttttgacaga     2340

gttggagcac agtgggattg gaagaatcaa agagcagagt gcccgcatgc tggggcacct     2400

ggtctccaat gccccccgac tcatccgccc ctacatggag cctattctga aggcattaat     2460

tttgaaactg aaagatccag accctgatcc aaacccaggt gtgatcaata atgtcctggc     2520

aacaatagga gaattggcac aggttagtgg cctggaaatg aggaaatggg ttgatgaact     2580

ttttattatc atcatggaca tgctccagga ttcctctttg ttggccaaaa ggcaggtggc     2640

tctgtggacc ctgggacagt tggtggccag cactggctat gtagtagagc cctacaggaa     2700

gtaccctact ttgcttgagg tgctactgaa ttttctgaag actgagcaga accagggtac     2760

acgcagagag gccatccgtg tgttagggct tttaggggct ttggatcctt acaagcacaa     2820

agtgaacatt ggcatgatag accagtcccg ggatgcctct gctgtcagcc tgtcagaatc     2880

caagtcaagt caggattcct ctgactatag cactagtgaa atgctggtca acatgggaaa     2940

cttgcctctg gatgagttct acccagctgt gtccatggtg gccctgatgc ggatcttccg     3000

agaccagtca ctctctcatc atcacaccat ggttgtccag gccatcacct tcatcttcaa     3060

gtccctggga ctcaaatgtg tgcagttcct gccccaggtc atgcccacgt tccttaacgt     3120

cattcgagtc tgtgatgggg ccatccggga atttttgttc cagcagctgg gaatgttggt     3180

gtcctttgtg aagagccaca tcagacctta tatggatgaa atagtcaccc tcatgagaga     3240

attctgggtc atgaacacct caattcagag cacgatcatt cttctcattg agcaaattgt     3300

ggtagctctt gggggtgaat ttaagctcta cctgccccag ctgatcccac acatgctgcg     3360

tgtcttcatg catgacaaca gcccaggccg cattgtctct atcaagttac tggctgcaat     3420

ccagctgttt ggcgccaacc tggatgacta cctgcattta ctgctgcctc ctattgttaa     3480

gttgtttgat gcccctgaag ctccactgcc atctcgaaag gcagcgctag agactgtgga     3540

ccgcctgacg gagtccctgg atttcactga ctatgcctcc cggatcattc accctattgt     3600

tcgaacactg gaccagagcc cagaactgcg ctccacagcc atggacacgc tgtcttcact     3660

tgtttttcag ctggggaaga agtaccaaat tttcattcca atggtgaata aagttctggt     3720

gcgacaccga atcaatcatc agcgctatga tgtgctcatc tgcagaattg tcaagggata     3780

cacacttgct gatgaagagg aggatccttt gatttaccag catcggatgc ttaggagtgg     3840

ccaaggggat gcattggcta gtggaccagt ggaaacagga cccatgaaga aactgcacgt     3900

cagcaccatc aacctccaaa aggcctgggg cgctgccagg agggtctcca aagatgactg     3960

gctggaatgg ctgagacggc tgagcctgga gctgctgaag gactcatcat cgccctccct     4020

gcgctcctgc tgggccctgg cacaggccta caacccgatg gccagggatc tcttcaatgc     4080

tgcatttgtg tcctgctggt ctgaactgaa tgaagatcaa caggatgagc tcatcagaag     4140

catcgagttg gccctcacct cacaagacat cgctgaagtc acacagaccc tcttaaactt     4200

ggctgaattc atggaacaca gtgacaaggg ccccctgcca ctgagagatg acaatggcat     4260

tgttctgctg ggtgagagag ctgccaagtg ccgagcatat gccaaagcac tacactacaa     4320

agaactggag ttccagaaag gccccacccc tgccattcta gaatctctca tcagcattaa     4380

taataagcta cagcagccgg aggcagcggc cggagtgtta gaatatgcca tgaaacactt     4440

tggagagctg gagatccagg ctacctggta tgagaaactg cacgagtggg aggatgccct     4500

tgtggcctat gacaagaaaa tggacaccaa caaggacgac ccagagctga tgctgggccg     4560

catgcgctgc ctcgaggcct tgggggaatg gggtcaactc caccagcagt gctgtgaaaa     4620

gtggaccctg gttaatgatg agacccaagc caagatggcc cggatggctg ctgcagctgc     4680

atggggttta ggtcagtggg acagcatgga agaatacacc tgtatgatcc ctcgggacac     4740

ccatgatggg gcattttata gagctgtgct ggcactgcat caggacctct tctccttggc     4800

acaacagtgc attgacaagg ccagggacct gctggatgct gaattaactg cgatggcagg     4860

agagagttac agtcgggcat atggggccat ggtttcttgc cacatgctgt ccgagctgga     4920

ggaggttatc cagtacaaac ttgtccccga gcgacgagag atcatccgcc agatctggtg     4980

ggagagactg cagggctgcc agcgtatcgt agaggactgg cagaaaatcc ttatggtgcg     5040

gtcccttgtg gtcagccctc atgaagacat gagaacctgg ctcaagtatg caagcctgtg     5100

cggcaagagt ggcaggctgg ctcttgctca taaaacttta gtgttgctcc tgggagttga     5160

tccgtctcgg caacttgacc atcctctgcc aacagttcac cctcaggtga cctatgccta     5220

catgaaaaac atgtggaaga gtgcccgcaa gatcgatgcc ttccagcaca tgcagcattt     5280

tgtccagacc atgcagcaac aggcccagca tgccatcgct actgaggacc agcagcataa     5340

gcaggaactg cacaagctca tggcccgatg cttcctgaaa cttggagagt ggcagctgaa     5400

tctacagggc atcaatgaga gcacaatccc caaagtgctg cagtactaca gcgccgccac     5460

agagcacgac cgcagctggt acaaggcctg gcatgcgtgg gcagtgatga acttcgaagc     5520

tgtgctacac tacaaacatc agaaccaagc ccgcgatgag aagaagaaac tgcgtcatgc     5580

cagcggggcc aacatcacca acgccaccac tgccgccacc acggccgcca ctgccaccac     5640

cactgccagc accgagggca gcaacagtga gagcgaggcc gagagcaccg agaacagccc     5700

caccccatcg ccgctgcaga agaaggtcac tgaggatctg tccaaaaccc tcctgatgta     5760

cacggtgcct gccgtccagg gcttcttccg ttccatctcc ttgtcacgag gcaacaacct     5820

ccaggataca ctcagagttc tcaccttatg gtttgattat ggtcactggc cagatgtcaa     5880

tgaggcctta gtggaggggg tgaaagccat ccagattgat acctggctac aggttatacc     5940

tcagctcatt gcaagaattg atacgcccag acccttggtg ggacgtctca ttcaccagct     6000

tctcacagac attggtcggt accaccccca ggccctcatc tacccactga cagtggcttc     6060

taagtctacc acgacagccc ggcacaatgc agccaacaag attctgaaga acatgtgtga     6120

gcacagcaac accctggtcc agcaggccat gatggtgagc gaggagctga tccgagtggc     6180

catcctctgg catgagatgt ggcatgaagg cctggaagag gcatctcgtt tgtactttgg     6240

ggaaaggaac gtgaaaggca tgtttgaggt gctggagccc ttgcatgcta tgatggaacg     6300

gggcccccag actctgaagg aaacatcctt taatcaggcc tatggtcgag atttaatgga     6360

ggcccaagag tggtgcagga agtacatgaa atcagggaat gtcaaggacc tcacccaagc     6420

ctgggacctc tattatcatg tgttccgacg aatctcaaag cagctgcctc agctcacatc     6480

cttagagctg caatatgttt ccccaaaact tctgatgtgc cgggaccttg aattggctgt     6540

gccaggaaca tatgacccca accagccaat cattcgcatt cagtccatag caccgtcttt     6600

gcaagtcatc acatccaagc agaggccccg gaaattgaca cttatgggca gcaacggaca     6660

tgagtttgtt ttccttctaa aaggccatga agatctgcgc caggatgagc gtgtgatgca     6720

gctcttcggc ctggttaaca cccttctggc caatgaccca acatctcttc ggaaaaacct     6780

cagcatccag agatacgctg tcatcccttt atcgaccaac tcgggcctca ttggctgggt     6840

tccccactgt gacacactgc acgccctcat ccgggactac agggagaaga agaagatcct     6900

tctcaacatc gagcatcgca tcatgttgcg gatggctccg gactatgacc acttgactct     6960

gatgcagaag gtggaggtgt ttgagcatgc cgtcaataat acagctgggg acgacctggc     7020

caagctgctg tggctgaaaa gccccagctc cgaggtgtgg tttgaccgaa gaaccaatta     7080

tacccgttct ttagcggtca tgtcaatggt tgggtatatt ttaggcctgg gagatagaca     7140

cccatccaac ctgatgctgg accgtctgag tgggaagatc ctgcacattg actttgggga     7200

ctgctttgag gttgctatga cccgagagaa gtttccagag aagattccat ttagactaac     7260

aagaatgttg accaatgcta tggaggttac aggcctggat ggcaactaca gaatcacatg     7320

ccacacagtg atggaggtgc tgcgagagca caaggacagt gtcatggccg tgctggaagc     7380

ctttgtctat gaccccttgc tgaactggag gctgatggac acaaatacca aaggcaacaa     7440

gcgatcccga acgaggacgg attcctactc tgctggccag tcagtcgaaa ttttggacgg     7500

tgtggaactt ggagagccag cccataagaa aacggggacc acagtgccag aatctattca     7560

ttctttcatt ggagacggtt tggtgaaacc agaggcccta aataagaaag ctatccagat     7620

tattaacagg gttcgagata agctcactgg tcgggacttc tctcatgatg acactttgga     7680

tgttccaacg caagttgagc tgctcatcaa acaagcgaca tcccatgaaa acctctgcca     7740

gtgctatatt ggctggtgcc ctttctggta actggaggcc cagatgtgcc catcacgttt     7800

tttctgaggc ttttgtactt tagtaaatgc ttccactaaa ctgaaaccat ggtgagaaag     7860

tttgactttg ttaaatattt tgaaatgtaa atgaaaagaa ctactgtata ttaaaagttg     7920

gtttgaacca actttctagc tgctgttgaa gaatatattg tcagaaacac aaggcttgat     7980

ttggttccca ggacagtgaa acatagtaat accacgtaaa tcaagccatt cattttgggg     8040

aacagaagat ccataacttt agaaatacgg gttttgactt aactcacaag agaactcatc     8100

ataagtactt gctgatggaa gaatgaccta gttgctcctc tcaacatggg tacagcaaac     8160

tcagcacagc caagaagcct caggtcgtgg agaacatgga ttaggatcct agactgtaaa     8220

gacacagaag atgctgacct cacccctgcc acctatccca agacctcact ggtctgtgga     8280

cagcagcaga aatgtttgca agataggcca aaatgagtac aaaaggtctg tcttccatca     8340

gacccagtga tgctgcgact cacacgcttc aattcaagac ctgaccgcta gtagggaggt     8400

ttattcagat cgctggcagc ctcggctgag cagatgcaca gaggggatca ctgtgcagtg     8460

ggaccaccct cactggcctt ctgcagcagg gttctgggat gttttcagtg gtcaaaatac     8520

tctgtttaga gcaagggctc agaaaacaga aatactgtca tggaggtgct gaacacaggg     8580

aaggtctggt acatattgga aattatgagc agaacaaata ctcaactaaa tgcacaaagt     8640

ataaagtgta gccatgtcta gacaccatgt tgtatcagaa taatttttgt gccaataaat     8700

gacatcagaa ttttaaacat atgtaaaaaa aaa                                  8733


<210>  3
<211>  108
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 
1               5                   10                  15      


Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 
            20                  25                  30          


Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 
        35                  40                  45              


Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu Gly Val 
    50                  55                  60                  


Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser Pro Asp 
65                  70                  75                  80  


Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro His Ala 
                85                  90                  95      


Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu 
            100                 105             


<210>  4
<211>  118
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Ser Gly Gly Ser Ser Cys Ser Gln Thr Pro Ser Arg Ala Ile Pro 
1               5                   10                  15      


Ala Thr Arg Arg Val Val Leu Gly Asp Gly Val Gln Leu Pro Pro Gly 
            20                  25                  30          


Asp Tyr Ser Thr Thr Pro Gly Gly Thr Leu Phe Ser Thr Thr Pro Gly 
        35                  40                  45              


Gly Thr Arg Ile Ile Tyr Asp Arg Lys Phe Leu Met Glu Cys Arg Asn 
    50                  55                  60                  


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


Val Thr Ser Pro Ser Ser Asp Glu Pro Pro Met Glu Ala Ser Gln Ser 
                85                  90                  95      


His Leu Arg Asn Ser Pro Glu Asp Lys Arg Ala Gly Gly Glu Glu Ser 
            100                 105                 110         


Gln Phe Glu Met Asp Ile 
        115             


<210>  5
<211>  480
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Ser Asp Val Ala Ile Val Lys Glu Gly Trp Leu His Lys Arg Gly 
1               5                   10                  15      


Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys Asn Asp 
            20                  25                  30          


Gly Thr Phe Ile Gly Tyr Lys Glu Arg Pro Gln Asp Val Asp Gln Arg 
        35                  40                  45              


Glu Ala Pro Leu Asn Asn Phe Ser Val Ala Gln Cys Gln Leu Met Lys 
    50                  55                  60                  


Thr Glu Arg Pro Arg Pro Asn Thr Phe Ile Ile Arg Cys Leu Gln Trp 
65                  70                  75                  80  


Thr Thr Val Ile Glu Arg Thr Phe His Val Glu Thr Pro Glu Glu Arg 
                85                  90                  95      


Glu Glu Trp Thr Thr Ala Ile Gln Thr Val Ala Asp Gly Leu Lys Lys 
            100                 105                 110         


Gln Glu Glu Glu Glu Met Asp Phe Arg Ser Gly Ser Pro Ser Asp Asn 
        115                 120                 125             


Ser Gly Ala Glu Glu Met Glu Val Ser Leu Ala Lys Pro Lys His Arg 
    130                 135                 140                 


Val Thr Met Asn Glu Phe Glu Tyr Leu Lys Leu Leu Gly Lys Gly Thr 
145                 150                 155                 160 


Phe Gly Lys Val Ile Leu Val Lys Glu Lys Ala Thr Gly Arg Tyr Tyr 
                165                 170                 175     


Ala Met Lys Ile Leu Lys Lys Glu Val Ile Val Ala Lys Asp Glu Val 
            180                 185                 190         


Ala His Thr Leu Thr Glu Asn Arg Val Leu Gln Asn Ser Arg His Pro 
        195                 200                 205             


Phe Leu Thr Ala Leu Lys Tyr Ser Phe Gln Thr His Asp Arg Leu Cys 
    210                 215                 220                 


Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His Leu Ser 
225                 230                 235                 240 


Arg Glu Arg Val Phe Ser Glu Asp Arg Ala Arg Phe Tyr Gly Ala Glu 
                245                 250                 255     


Ile Val Ser Ala Leu Asp Tyr Leu His Ser Glu Lys Asn Val Val Tyr 
            260                 265                 270         


Arg Asp Leu Lys Leu Glu Asn Leu Met Leu Asp Lys Asp Gly His Ile 
        275                 280                 285             


Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly Ile Lys Asp Gly Ala 
    290                 295                 300                 


Thr Met Lys Thr Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val 
305                 310                 315                 320 


Leu Glu Asp Asn Asp Tyr Gly Arg Ala Val Asp Trp Trp Gly Leu Gly 
                325                 330                 335     


Val Val Met Tyr Glu Met Met Cys Gly Arg Leu Pro Phe Tyr Asn Gln 
            340                 345                 350         


Asp His Glu Lys Leu Phe Glu Leu Ile Leu Met Glu Glu Ile Arg Phe 
        355                 360                 365             


Pro Arg Thr Leu Gly Pro Glu Ala Lys Ser Leu Leu Ser Gly Leu Leu 
    370                 375                 380                 


Lys Lys Asp Pro Lys Gln Arg Leu Gly Gly Gly Ser Glu Asp Ala Lys 
385                 390                 395                 400 


Glu Ile Met Gln His Arg Phe Phe Ala Gly Ile Val Trp Gln His Val 
                405                 410                 415     


Tyr Glu Lys Lys Leu Ser Pro Pro Phe Lys Pro Gln Val Thr Ser Glu 
            420                 425                 430         


Thr Asp Thr Arg Tyr Phe Asp Glu Glu Phe Thr Ala Gln Met Ile Thr 
        435                 440                 445             


Ile Thr Pro Pro Asp Gln Asp Asp Ser Met Glu Cys Val Asp Ser Glu 
    450                 455                 460                 


Arg Arg Pro His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Gly Thr Ala 
465                 470                 475                 480 


