                         SEQUENCE LISTING

<110>  Garraway, Levi
       Wagle, Nikhil
       Emery, Caroline
 
<120>  A MEK1 MUTATION CONFERRING RESISTANCE TO RAF AND MEK INHIBITORS

<130>  14293/87

<150>  US 61/352,959
<151>  2010-06-09

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  2603
<212>  DNA
<213>  Homo sapiens

<400>  1
aggcgaggct tccccttccc cgcccctccc ccggcctcca gtccctccca gggccgcttc       60

gcagagcggc taggagcacg gcggcggcgg cactttcccc ggcaggagct ggagctgggc      120

tctggtgcgc gcgcggctgt gccgcccgag ccggagggac tggttggttg agagagagag      180

aggaagggaa tcccgggctg ccgaaccgca cgttcagccc gctccgctcc tgcagggcag      240

cctttcggct ctctgcgcgc gaagccgagt cccgggcggg tggggcgggg gtccactgag      300

accgctaccg gcccctcggc gctgacggga ccgcgcgggg cgcacccgct gaaggcagcc      360

ccggggcccg cggcccggac ttggtcctgc gcagcgggcg cggggcagcg cagcgggagg      420

aagcgagagg tgctgccctc cccccggagt tggaagcgcg ttacccgggt ccaaaatgcc      480

caagaagaag ccgacgccca tccagctgaa cccggccccc gacggctctg cagttaacgg      540

gaccagctct gcggagacca acttggaggc cttgcagaag aagctggagg agctagagct      600

tgatgagcag cagcgaaagc gccttgaggc ctttcttacc cagaagcaga aggtgggaga      660

actgaaggat gacgactttg agaagatcag tgagctgggg gctggcaatg gcggtgtggt      720

gttcaaggtc tcccacaagc cttctggcct ggtcatggcc agaaagctaa ttcatctgga      780

gatcaaaccc gcaatccgga accagatcat aagggagctg caggttctgc atgagtgcaa      840

ctctccgtac atcgtgggct tctatggtgc gttctacagc gatggcgaga tcagtatctg      900

catggagcac atggatggag gttctctgga tcaagtcctg aagaaagctg gaagaattcc      960

tgaacaaatt ttaggaaaag ttagcattgc tgtaataaaa ggcctgacat atctgaggga     1020

gaagcacaag atcatgcaca gagatgtcaa gccctccaac atcctagtca actcccgtgg     1080

ggagatcaag ctctgtgact ttggggtcag cgggcagctc atcgactcca tggccaactc     1140

cttcgtgggc acaaggtcct acatgtcgcc agaaagactc caggggactc attactctgt     1200

gcagtcagac atctggagca tgggactgtc tctggtagag atggcggttg ggaggtatcc     1260

catccctcct ccagatgcca aggagctgga gctgatgttt gggtgccagg tggaaggaga     1320

tgcggctgag accccaccca ggccaaggac ccccgggagg ccccttagct catacggaat     1380

ggacagccga cctcccatgg caatttttga gttgttggat tacatagtca acgagcctcc     1440

tccaaaactg cccagtggag tgttcagtct ggaatttcaa gattttgtga ataaatgctt     1500

aataaaaaac cccgcagaga gagcagattt gaagcaactc atggttcatg cttttatcaa     1560

gagatctgat gctgaggaag tggattttgc aggttggctc tgctccacca tcggccttaa     1620

ccagcccagc acaccaaccc atgctgctgg cgtctaagtg tttgggaagc aacaaagagc     1680

gagtcccctg cccggtggtt tgccatgtcg cttttgggcc tccttcccat gcctgtctct     1740

gttcagatgt gcatttcacc tgtgacaaag gatgaagaac acagcatgtg ccaagattct     1800

actcttgtca tttttaatat tactgtcttt attcttatta ctattattgt tcccctaagt     1860

ggattggctt tgtgcttggg gctatttgtg tgtatgctga tgatcaaaac ctgtgccagg     1920

ctgaattaca gtgaaatttt ggtgaatgtg ggtagtcatt cttacaattg cactgctgtt     1980

cctgctccat gactggctgt ctgcctgtat tttcgggatt ctttgacatt tggtggtact     2040

ttattcttgc tgggcatact ttctctctag gagggagcct tgtgagatcc ttcacaggca     2100

gtgcatgtga agcatgcttt gctgctatga aaatgagcat cagagagtgt acatcatgtt     2160

attttattat tattatttgc ttttcatgta gaactcagca gttgacatcc aaatctagcc     2220

agagcccttc actgccatga tagctggggc ttcaccagtc tgtctactgt ggtgatctgt     2280

agacttctgg ttgtatttct atatttattt tcagtatact gtgtgggata cttagtggta     2340

tgtctcttta agttttgatt aatgtttctt aaatggaatt attttgaatg tcacaaattg     2400

atcaagatat taaaatgtcg gatttatctt tccccatatc caagtaccaa tgctgttgta     2460

aacaacgtgt atagtgccta aaattgtatg aaaatccttt taaccatttt aacctagatg     2520

tttaacaaat ctaatctctt attctaataa atatactatg aaataaaaaa aaaaggatga     2580

aagctaaaaa aaaaaaaaaa aaa                                             2603


<210>  2
<211>  393
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Pro Lys Lys Lys Pro Thr Pro Ile Gln Leu Asn Pro Ala Pro Asp 
1               5                   10                  15      


Gly Ser Ala Val Asn Gly Thr Ser Ser Ala Glu Thr Asn Leu Glu Ala 
            20                  25                  30          


Leu Gln Lys Lys Leu Glu Glu Leu Glu Leu Asp Glu Gln Gln Arg Lys 
        35                  40                  45              


Arg Leu Glu Ala Phe Leu Thr Gln Lys Gln Lys Val Gly Glu Leu Lys 
    50                  55                  60                  


Asp Asp Asp Phe Glu Lys Ile Ser Glu Leu Gly Ala Gly Asn Gly Gly 
65                  70                  75                  80  


Val Val Phe Lys Val Ser His Lys Pro Ser Gly Leu Val Met Ala Arg 
                85                  90                  95      


Lys Leu Ile His Leu Glu Ile Lys Pro Ala Ile Arg Asn Gln Ile Ile 
            100                 105                 110         


Arg Glu Leu Gln Val Leu His Glu Cys Asn Ser Pro Tyr Ile Val Gly 
        115                 120                 125             


Phe Tyr Gly Ala Phe Tyr Ser Asp Gly Glu Ile Ser Ile Cys Met Glu 
    130                 135                 140                 


His Met Asp Gly Gly Ser Leu Asp Gln Val Leu Lys Lys Ala Gly Arg 
145                 150                 155                 160 


Ile Pro Glu Gln Ile Leu Gly Lys Val Ser Ile Ala Val Ile Lys Gly 
                165                 170                 175     


Leu Thr Tyr Leu Arg Glu Lys His Lys Ile Met His Arg Asp Val Lys 
            180                 185                 190         


Pro Ser Asn Ile Leu Val Asn Ser Arg Gly Glu Ile Lys Leu Cys Asp 
        195                 200                 205             


Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala Asn Ser Phe Val 
    210                 215                 220                 


Gly Thr Arg Ser Tyr Met Ser Pro Glu Arg Leu Gln Gly Thr His Tyr 
225                 230                 235                 240 


Ser Val Gln Ser Asp Ile Trp Ser Met Gly Leu Ser Leu Val Glu Met 
                245                 250                 255     


Ala Val Gly Arg Tyr Pro Ile Pro Pro Pro Asp Ala Lys Glu Leu Glu 
            260                 265                 270         


Leu Met Phe Gly Cys Gln Val Glu Gly Asp Ala Ala Glu Thr Pro Pro 
        275                 280                 285             


Arg Pro Arg Thr Pro Gly Arg Pro Leu Ser Ser Tyr Gly Met Asp Ser 
    290                 295                 300                 


Arg Pro Pro Met Ala Ile Phe Glu Leu Leu Asp Tyr Ile Val Asn Glu 
305                 310                 315                 320 


Pro Pro Pro Lys Leu Pro Ser Gly Val Phe Ser Leu Glu Phe Gln Asp 
                325                 330                 335     


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


Lys Gln Leu Met Val His Ala Phe Ile Lys Arg Ser Asp Ala Glu Glu 
        355                 360                 365             


Val Asp Phe Ala Gly Trp Leu Cys Ser Thr Ile Gly Leu Asn Gln Pro 
    370                 375                 380                 


Ser Thr Pro Thr His Ala Ala Gly Val 
385                 390             


<210>  3
<211>  2603
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (838)..(838)
<223>  n is a, c, g, or t

<400>  3
aggcgaggct tccccttccc cgcccctccc ccggcctcca gtccctccca gggccgcttc       60

gcagagcggc taggagcacg gcggcggcgg cactttcccc ggcaggagct ggagctgggc      120

tctggtgcgc gcgcggctgt gccgcccgag ccggagggac tggttggttg agagagagag      180

aggaagggaa tcccgggctg ccgaaccgca cgttcagccc gctccgctcc tgcagggcag      240

cctttcggct ctctgcgcgc gaagccgagt cccgggcggg tggggcgggg gtccactgag      300

accgctaccg gcccctcggc gctgacggga ccgcgcgggg cgcacccgct gaaggcagcc      360

ccggggcccg cggcccggac ttggtcctgc gcagcgggcg cggggcagcg cagcgggagg      420

aagcgagagg tgctgccctc cccccggagt tggaagcgcg ttacccgggt ccaaaatgcc      480

caagaagaag ccgacgccca tccagctgaa cccggccccc gacggctctg cagttaacgg      540

gaccagctct gcggagacca acttggaggc cttgcagaag aagctggagg agctagagct      600

tgatgagcag cagcgaaagc gccttgaggc ctttcttacc cagaagcaga aggtgggaga      660

actgaaggat gacgactttg agaagatcag tgagctgggg gctggcaatg gcggtgtggt      720

gttcaaggtc tcccacaagc cttctggcct ggtcatggcc agaaagctaa ttcatctgga      780

gatcaaaccc gcaatccgga accagatcat aagggagctg caggttctgc atgagtcnaa      840

ctctccgtac atcgtgggct tctatggtgc gttctacagc gatggcgaga tcagtatctg      900

catggagcac atggatggag gttctctgga tcaagtcctg aagaaagctg gaagaattcc      960

tgaacaaatt ttaggaaaag ttagcattgc tgtaataaaa ggcctgacat atctgaggga     1020

gaagcacaag atcatgcaca gagatgtcaa gccctccaac atcctagtca actcccgtgg     1080

ggagatcaag ctctgtgact ttggggtcag cgggcagctc atcgactcca tggccaactc     1140

cttcgtgggc acaaggtcct acatgtcgcc agaaagactc caggggactc attactctgt     1200

gcagtcagac atctggagca tgggactgtc tctggtagag atggcggttg ggaggtatcc     1260

catccctcct ccagatgcca aggagctgga gctgatgttt gggtgccagg tggaaggaga     1320

tgcggctgag accccaccca ggccaaggac ccccgggagg ccccttagct catacggaat     1380

ggacagccga cctcccatgg caatttttga gttgttggat tacatagtca acgagcctcc     1440

tccaaaactg cccagtggag tgttcagtct ggaatttcaa gattttgtga ataaatgctt     1500

aataaaaaac cccgcagaga gagcagattt gaagcaactc atggttcatg cttttatcaa     1560

gagatctgat gctgaggaag tggattttgc aggttggctc tgctccacca tcggccttaa     1620

ccagcccagc acaccaaccc atgctgctgg cgtctaagtg tttgggaagc aacaaagagc     1680

gagtcccctg cccggtggtt tgccatgtcg cttttgggcc tccttcccat gcctgtctct     1740

gttcagatgt gcatttcacc tgtgacaaag gatgaagaac acagcatgtg ccaagattct     1800

actcttgtca tttttaatat tactgtcttt attcttatta ctattattgt tcccctaagt     1860

ggattggctt tgtgcttggg gctatttgtg tgtatgctga tgatcaaaac ctgtgccagg     1920

ctgaattaca gtgaaatttt ggtgaatgtg ggtagtcatt cttacaattg cactgctgtt     1980

cctgctccat gactggctgt ctgcctgtat tttcgggatt ctttgacatt tggtggtact     2040

ttattcttgc tgggcatact ttctctctag gagggagcct tgtgagatcc ttcacaggca     2100

gtgcatgtga agcatgcttt gctgctatga aaatgagcat cagagagtgt acatcatgtt     2160

attttattat tattatttgc ttttcatgta gaactcagca gttgacatcc aaatctagcc     2220

agagcccttc actgccatga tagctggggc ttcaccagtc tgtctactgt ggtgatctgt     2280

agacttctgg ttgtatttct atatttattt tcagtatact gtgtgggata cttagtggta     2340

tgtctcttta agttttgatt aatgtttctt aaatggaatt attttgaatg tcacaaattg     2400

atcaagatat taaaatgtcg gatttatctt tccccatatc caagtaccaa tgctgttgta     2460

aacaacgtgt atagtgccta aaattgtatg aaaatccttt taaccatttt aacctagatg     2520

tttaacaaat ctaatctctt attctaataa atatactatg aaataaaaaa aaaaggatga     2580

aagctaaaaa aaaaaaaaaa aaa                                             2603


<210>  4
<211>  393
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Pro Lys Lys Lys Pro Thr Pro Ile Gln Leu Asn Pro Ala Pro Asp 
1               5                   10                  15      


Gly Ser Ala Val Asn Gly Thr Ser Ser Ala Glu Thr Asn Leu Glu Ala 
            20                  25                  30          


Leu Gln Lys Lys Leu Glu Glu Leu Glu Leu Asp Glu Gln Gln Arg Lys 
        35                  40                  45              


Arg Leu Glu Ala Phe Leu Thr Gln Lys Gln Lys Val Gly Glu Leu Lys 
    50                  55                  60                  


Asp Asp Asp Phe Glu Lys Ile Ser Glu Leu Gly Ala Gly Asn Gly Gly 
65                  70                  75                  80  


Val Val Phe Lys Val Ser His Lys Pro Ser Gly Leu Val Met Ala Arg 
                85                  90                  95      


Lys Leu Ile His Leu Glu Ile Lys Pro Ala Ile Arg Asn Gln Ile Ile 
            100                 105                 110         


Arg Glu Leu Gln Val Leu His Glu Ser Asn Ser Pro Tyr Ile Val Gly 
        115                 120                 125             


Phe Tyr Gly Ala Phe Tyr Ser Asp Gly Glu Ile Ser Ile Cys Met Glu 
    130                 135                 140                 


His Met Asp Gly Gly Ser Leu Asp Gln Val Leu Lys Lys Ala Gly Arg 
145                 150                 155                 160 


Ile Pro Glu Gln Ile Leu Gly Lys Val Ser Ile Ala Val Ile Lys Gly 
                165                 170                 175     


Leu Thr Tyr Leu Arg Glu Lys His Lys Ile Met His Arg Asp Val Lys 
            180                 185                 190         


Pro Ser Asn Ile Leu Val Asn Ser Arg Gly Glu Ile Lys Leu Cys Asp 
        195                 200                 205             


Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala Asn Ser Phe Val 
    210                 215                 220                 


Gly Thr Arg Ser Tyr Met Ser Pro Glu Arg Leu Gln Gly Thr His Tyr 
225                 230                 235                 240 


Ser Val Gln Ser Asp Ile Trp Ser Met Gly Leu Ser Leu Val Glu Met 
                245                 250                 255     


Ala Val Gly Arg Tyr Pro Ile Pro Pro Pro Asp Ala Lys Glu Leu Glu 
            260                 265                 270         


Leu Met Phe Gly Cys Gln Val Glu Gly Asp Ala Ala Glu Thr Pro Pro 
        275                 280                 285             


Arg Pro Arg Thr Pro Gly Arg Pro Leu Ser Ser Tyr Gly Met Asp Ser 
    290                 295                 300                 


Arg Pro Pro Met Ala Ile Phe Glu Leu Leu Asp Tyr Ile Val Asn Glu 
305                 310                 315                 320 


Pro Pro Pro Lys Leu Pro Ser Gly Val Phe Ser Leu Glu Phe Gln Asp 
                325                 330                 335     


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


Lys Gln Leu Met Val His Ala Phe Ile Lys Arg Ser Asp Ala Glu Glu 
        355                 360                 365             


Val Asp Phe Ala Gly Trp Leu Cys Ser Thr Ile Gly Leu Asn Gln Pro 
    370                 375                 380                 


Ser Thr Pro Thr His Ala Ala Gly Val 
385                 390             


