SEQUENCE LISTING <110> Revolution Medicines, Inc. <120> ANÁLOGOS DE RAPAMICINA LIGADOS A C40, C28 Y C-32 COMO INHIBIDORES DE MTOR <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