                         SEQUENCE LISTING

<110>  ProtAffin Biotechnologie AG
 
<120>  FGFR-1 based antagonists with imnproved glycosaminoglycan 
       affinity and methods using the same

<130>  PA010P

<160>  20    

<170>  PatentIn version 3.3

<210>  1
<211>  822
<212>  PRT
<213>  human

<400>  1

Met Trp Ser Trp Lys Cys Leu Leu Phe Trp Ala Val Leu Val Thr Ala 
1               5                   10                  15      


Thr Leu Cys Thr Ala Arg Pro Ser Pro Thr Leu Pro Glu Gln Ala Gln 
            20                  25                  30          


Pro Trp Gly Ala Pro Val Glu Val Glu Ser Phe Leu Val His Pro Gly 
        35                  40                  45              


Asp Leu Leu Gln Leu Arg Cys Arg Leu Arg Asp Asp Val Gln Ser Ile 
    50                  55                  60                  


Asn Trp Leu Arg Asp Gly Val Gln Leu Ala Glu Ser Asn Arg Thr Arg 
65                  70                  75                  80  


Ile Thr Gly Glu Glu Val Glu Val Gln Asp Ser Val Pro Ala Asp Ser 
                85                  90                  95      


Gly Leu Tyr Ala Cys Val Thr Ser Ser Pro Ser Gly Ser Asp Thr Thr 
            100                 105                 110         


Tyr Phe Ser Val Asn Val Ser Asp Ala Leu Pro Ser Ser Glu Asp Asp 
        115                 120                 125             


Asp Asp Asp Asp Asp Ser Ser Ser Glu Glu Lys Glu Thr Asp Asn Thr 
    130                 135                 140                 


Lys Pro Asn Arg Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys 
145                 150                 155                 160 


Met Glu Lys Lys Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe 
                165                 170                 175     


Lys Cys Pro Ser Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys 
            180                 185                 190         


Asn Gly Lys Glu Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val 
        195                 200                 205             


Arg Tyr Ala Thr Trp Ser Ile Ile Met Asp Ser Val Val Pro Ser Asp 
    210                 215                 220                 


Lys Gly Asn Tyr Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn 
225                 230                 235                 240 


His Thr Tyr Gln Leu Asp Val Val Glu Arg Ser Pro His Arg Pro Ile 
                245                 250                 255     


Leu Gln Ala Gly Leu Pro Ala Asn Lys Thr Val Ala Leu Gly Ser Asn 
            260                 265                 270         


Val Glu Phe Met Cys Lys Val Tyr Ser Asp Pro Gln Pro His Ile Gln 
        275                 280                 285             


Trp Leu Lys His Ile Glu Val Asn Gly Ser Lys Ile Gly Pro Asp Asn 
    290                 295                 300                 


Leu Pro Tyr Val Gln Ile Leu Lys Thr Ala Gly Val Asn Thr Thr Asp 
305                 310                 315                 320 


Lys Glu Met Glu Val Leu His Leu Arg Asn Val Ser Phe Glu Asp Ala 
                325                 330                 335     


Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Leu Ser His His 
            340                 345                 350         


Ser Ala Trp Leu Thr Val Leu Glu Ala Leu Glu Glu Arg Pro Ala Val 
        355                 360                 365             


Met Thr Ser Pro Leu Tyr Leu Glu Ile Ile Ile Tyr Cys Thr Gly Ala 
    370                 375                 380                 


Phe Leu Ile Ser Cys Met Val Gly Ser Val Ile Val Tyr Lys Met Lys 
385                 390                 395                 400 


Ser Gly Thr Lys Lys Ser Asp Phe His Ser Gln Met Ala Val His Lys 
                405                 410                 415     


Leu Ala Lys Ser Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala Asp 
            420                 425                 430         


Ser Ser Ala Ser Met Asn Ser Gly Val Leu Leu Val Arg Pro Ser Arg 
        435                 440                 445             


Leu Ser Ser Ser Gly Thr Pro Met Leu Ala Gly Val Ser Glu Tyr Glu 
    450                 455                 460                 


Leu Pro Glu Asp Pro Arg Trp Glu Leu Pro Arg Asp Arg Leu Val Leu 
465                 470                 475                 480 


Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val Val Leu Ala Glu 
                485                 490                 495     


Ala Ile Gly Leu Asp Lys Asp Lys Pro Asn Arg Val Thr Lys Val Ala 
            500                 505                 510         


Val Lys Met Leu Lys Ser Asp Ala Thr Glu Lys Asp Leu Ser Asp Leu 
        515                 520                 525             


Ile Ser Glu Met Glu Met Met Lys Met Ile Gly Lys His Lys Asn Ile 
    530                 535                 540                 


Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro Leu Tyr Val Ile 
545                 550                 555                 560 


Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr Leu Gln Ala Arg 
                565                 570                 575     


Arg Pro Pro Gly Leu Glu Tyr Cys Tyr Asn Pro Ser His Asn Pro Glu 
            580                 585                 590         


Glu Gln Leu Ser Ser Lys Asp Leu Val Ser Cys Ala Tyr Gln Val Ala 
        595                 600                 605             


Arg Gly Met Glu Tyr Leu Ala Ser Lys Lys Cys Ile His Arg Asp Leu 
    610                 615                 620                 


Ala Ala Arg Asn Val Leu Val Thr Glu Asp Asn Val Met Lys Ile Ala 
625                 630                 635                 640 


Asp Phe Gly Leu Ala Arg Asp Ile His His Ile Asp Tyr Tyr Lys Lys 
                645                 650                 655     


Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu 
            660                 665                 670         


Phe Asp Arg Ile Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly Val 
        675                 680                 685             


Leu Leu Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro Gly Val 
    690                 695                 700                 


Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His Arg Met Asp 
705                 710                 715                 720 


Lys Pro Ser Asn Cys Thr Asn Glu Leu Tyr Met Met Met Arg Asp Cys 
                725                 730                 735     


Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu 
            740                 745                 750         


Asp Leu Asp Arg Ile Val Ala Leu Thr Ser Asn Gln Glu Tyr Leu Asp 
        755                 760                 765             


Leu Ser Met Pro Leu Asp Gln Tyr Ser Pro Ser Phe Pro Asp Thr Arg 
    770                 775                 780                 


Ser Ser Thr Cys Ser Ser Gly Glu Asp Ser Val Phe Ser His Glu Pro 
785                 790                 795                 800 


Leu Pro Glu Glu Pro Cys Leu Pro Arg His Pro Ala Gln Leu Ala Asn 
                805                 810                 815     


Gly Gly Leu Lys Arg Arg 
            820         


<210>  2
<211>  100
<212>  PRT
<213>  artificial

<220>
<223>  FGFR1 with affinity tag

<400>  2

His His His His His His Ser Met Gly Thr Lys Pro Asn Arg Met Pro 
1               5                   10                  15      


Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys Leu His 
            20                  25                  30          


Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser Ser Gly 
        35                  40                  45              


Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu Phe Lys 
    50                  55                  60                  


Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Tyr Ala Thr Trp Ser 
65                  70                  75                  80  


Ile Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr Thr Cys 
                85                  90                  95      


Ile Val Glu Asn 
            100 


<210>  3
<211>  116
<212>  PRT
<213>  human

<400>  3

Met Ser His His His His His His Ser Met Gly Thr Lys Pro Asn Arg 
1               5                   10                  15      


Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys 
            20                  25                  30          


Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser 
        35                  40                  45              


Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu 
    50                  55                  60                  


Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Tyr Ala Thr 
65                  70                  75                  80  


Trp Ser Ile Ile Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr 
                85                  90                  95      


Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln 
            100                 105                 110         


Leu Asp Val Val 
        115     


<210>  4
<211>  116
<212>  PRT
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  4

Met Ser His His His His His His Ser Met Gly Thr Lys Pro Asn Arg 
1               5                   10                  15      


Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys 
            20                  25                  30          


Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser 
        35                  40                  45              


Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu 
    50                  55                  60                  


Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Lys Ala Thr 
65                  70                  75                  80  


Trp Ser Ile Lys Met Asp Ser Val Val Pro Ser Asp Lys Gly Asn Tyr 
                85                  90                  95      


Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln 
            100                 105                 110         


Leu Asp Val Val 
        115     


<210>  5
<211>  116
<212>  PRT
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  5

Met Ser His His His His His His Ser Met Gly Thr Lys Pro Asn Arg 
1               5                   10                  15      


Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys 
            20                  25                  30          


Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser 
        35                  40                  45              


Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu 
    50                  55                  60                  


Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Lys Ala Thr 
65                  70                  75                  80  


Trp Ser Ile Ile Met Lys Ser Val Val Pro Ser Asp Lys Gly Asn Tyr 
                85                  90                  95      


Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln 
            100                 105                 110         


Leu Asp Val Val 
        115     


<210>  6
<211>  116
<212>  PRT
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  6

Met Ser His His His His His His Ser Met Gly Thr Lys Pro Asn Arg 
1               5                   10                  15      


Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys 
            20                  25                  30          


Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser 
        35                  40                  45              


Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu 
    50                  55                  60                  


Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Tyr Ala Thr 
65                  70                  75                  80  


Trp Ser Ile Lys Met Lys Ser Val Val Pro Ser Asp Lys Gly Asn Tyr 
                85                  90                  95      


Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln 
            100                 105                 110         


Leu Asp Val Val 
        115     


<210>  7
<211>  116
<212>  PRT
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  7

Met Ser His His His His His His Ser Met Gly Thr Lys Pro Asn Arg 
1               5                   10                  15      


Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu Lys Met Glu Lys Lys 
            20                  25                  30          


Leu His Ala Val Pro Ala Ala Lys Thr Val Lys Phe Lys Cys Pro Ser 
        35                  40                  45              


Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu Lys Asn Gly Lys Glu 
    50                  55                  60                  


Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys Val Arg Lys Ala Thr 
65                  70                  75                  80  


Trp Ser Ile Lys Met Lys Ser Val Val Pro Ser Asp Lys Gly Asn Tyr 
                85                  90                  95      


Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile Asn His Thr Tyr Gln 
            100                 105                 110         


Leu Asp Val Val 
        115     


<210>  8
<211>  4746
<212>  DNA
<213>  artificial

<220>
<223>  pHAT2/FGFR1 mutant

<400>  8
taatacgact cactataggg aattgtgagc ggataacaat tcctctagaa ataattttgt     60

ttaactttaa gaaggagata tatccatgag tcatcaccat caccatcact ccatggggac    120

caaaccaaac cgtatgcccg tagctccata ttggacatcc ccagaaaaga tggaaaagaa    180

attgcatgca gtgccggctg ccaagacagt gaagttcaaa tgcccttcca gtgggacccc    240

aaaccccaca ctgcgctggt tgaaaaatgg caaagaattc aaacctgacc acagaattgg    300

aggctacaag gtccgttatg ccacctggag catcataatg gactctgtgg tgccctctga    360

caagggcaac tacacctgca ttgtggagaa tgagtacggc agcatcaacc acacatacca    420

gctggatgtc gtgtaactcg agggatccgg gccctctaga tgcggccgca tgcataagct    480

tgagtattct atagtgtcac ctaaatccca gcttgatccg gctgctaaca aagcccgaaa    540

ggaagctgag ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc    600

taaacgggtc ttgaggggtt ttttgctgaa aggaggaact atatccggat aacctggcgt    660

aatagcgaag aggcccgcac cgatcgccct tcccaacagt tgcgcagcct gaatggcgaa    720

tggaaattgt aaacgttaat attttgttaa aattcgcgtt aaatatttgt taaatcagct    780

cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg    840

agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact    900

ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacag cttgcatgcc    960

tgcaggtcgg aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat   1020

taattgcgtt gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt   1080

aatgaatcgg ccaacgcgcg gggagaggcg gtttgcgtat tgggcgccag ggtggttttt   1140

cttttcacca gtgagacggg caacagctga ttgcccttca ccgcctggcc ctgagagagt   1200

tgcagcaagc ggtccacgct ggtttgcccc agcaggcgaa aatcctgttt gatggtggtt   1260

gacggcggga tataacatga gctgtcttcg gtatcgtcgt atcccactac cgagatatcc   1320

gcaccaacgc gcagcccgga ctcggtaatg gcgcgcattg cgcccagcgc catctgatcg   1380

ttggcaacca gcatcgcagt gggaacgatg ccctcattca gcatttgcat ggtttgttga   1440

aaaccggaca tggcactcca gtcgccttcc cgttccgcta tcggctgaat ttgattgcga   1500

gtgagatatt tatgccagcc agccagacgc agacgcgccg agacagaact taatgggccc   1560

gctaacagcg cgatttgctg gtgacccaat gcgaccagat gctccacgcc cagtcgcgta   1620

ccgtcttcat gggagaaaat aatactgttg atgggtgtct ggtcagagac atcaagaaat   1680

aacgccggaa cattagtgca ggcagcttcc acagcaatgg catcctggtc atccagcgga   1740

tagttaatga tcagcccact gacgcgttgc gcgagaagat tgtgcaccgc cgctttacag   1800

gcttcgacgc cgcttcgttc taccatcgac accaccacgc tggcacccag ttgatcggcg   1860

cgagatttaa tcgccgcgac aatttgcgac ggcgcgtgca gggccagact ggaggtggca   1920

acgccaatca gcaacgactg tttgcccgcc agttgttgtg ccacgcggtt gggaatgtaa   1980

ttcagctccg ccatcgccgc ttccactttt tcccgcgttt tcgcagaaac gtggctggcc   2040

tggttcacca cgcgggaaac ggtctgataa gagacaccgg catactctgc gacatcgtat   2100

aacgttactg gtttcacatt caccaccctg aattgactct cttccgggcg ctatcatgcc   2160

ataccgcgaa aggttttgca ccattcgatg gtgtcgggta ccgagctcga atttacgtga   2220

accatcaccc aaatcaagtt ttttgcggtc gaggtgccgt aaagctctaa atcggaaccc   2280

taaagggagc ccccgattta gagcttgacg gggaaagccg gcgaacgtgg cgagaaagga   2340

agggaagaaa gcgaaaggag cgggcgctag ggcgctggca agtgtagcgg tcacgctgcg   2400

cgtaaccacc acacccgccg cgcttaatgc gccgctacag ggcgcgtcgc ctgatgcggt   2460

attttctcct tacgcatctg tgcggtattt cacaccgcat atggtgcact ctcagtacaa   2520

tctgctctga tgccgcatag ttaagccagc cccgacaccc gccaacaccc gctgacgcgc   2580

cctgacgggc ttgtctgctc ccggcatccg cttacagaca agctgtgacc gtctccggga   2640

gctgcatgtg tcagaggttt tcaccgtcat caccgaaacg cgcgagacga aagggcctcg   2700

tgatacgcct atttttatag gttaatgtca tgataataat ggtttcttag acgtcaggtg   2760

gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa atacattcaa   2820

atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat tgaaaaagga   2880

agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg gcattttgcc   2940

ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg   3000

gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt gagagttttc   3060

gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt catacactat   3120

tatcccgtat tgacgccggg caagagcaac tcggtcgccg ggcgcggtat tctcagaatg   3180

acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg acagtaagag   3240

aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta cttctgacaa   3300

cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat catgtaactc   3360

gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag cgtgacacca   3420

cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa ctacttactc   3480

tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca ggaccacttc   3540

tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc ggtgagcgtg   3600

ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt atcgtagtta   3660

tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc gctgagatag   3720

gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat atactttaga   3780

ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt tttgataatc   3840

tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac cccgtagaaa   3900

agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa   3960

aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc   4020

cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta gtgtagccgt   4080

agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc   4140

tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac   4200

gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca   4260

gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg   4320

ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag   4380

gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt cctgtcgggt   4440

ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg cggagcctat   4500

ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg ccttttgctc   4560

acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc gcctttgagt   4620

gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg agcgaggaag   4680

cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt cattaatgca   4740

gctgat                                                              4746


<210>  9
<211>  4746
<212>  DNA
<213>  artificial

<220>
<223>  pHAT2/FGFR1 mutant

<400>  9
taatacgact cactataggg aattgtgagc ggataacaat tcctctagaa ataattttgt     60

ttaactttaa gaaggagata tatccatgag tcatcaccat caccatcact ccatggggac    120

caaaccaaac cgtatgcccg tagctccata ttggacatcc ccagaaaaga tggaaaagaa    180

attgcatgca gtgccggctg ccaagacagt gaagttcaaa tgcccttcca gtgggacccc    240

aaaccccaca ctgcgctggt tgaaaaatgg caaagaattc aaacctgacc acagaattgg    300

aggctacaag gtccgtaaag ccacctggag catcaaaatg gactctgtgg tgccctctga    360

caagggcaac tacacctgca ttgtggagaa tgagtacggc agcatcaacc acacatacca    420

gctggatgtc gtgtaactcg agggatccgg gccctctaga tgcggccgca tgcataagct    480

tgagtattct atagtgtcac ctaaatccca gcttgatccg gctgctaaca aagcccgaaa    540

ggaagctgag ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc    600

taaacgggtc ttgaggggtt ttttgctgaa aggaggaact atatccggat aacctggcgt    660

aatagcgaag aggcccgcac cgatcgccct tcccaacagt tgcgcagcct gaatggcgaa    720

tggaaattgt aaacgttaat attttgttaa aattcgcgtt aaatatttgt taaatcagct    780

cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg    840

agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact    900

ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacag cttgcatgcc    960

tgcaggtcgg aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat   1020

taattgcgtt gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt   1080

aatgaatcgg ccaacgcgcg gggagaggcg gtttgcgtat tgggcgccag ggtggttttt   1140

cttttcacca gtgagacggg caacagctga ttgcccttca ccgcctggcc ctgagagagt   1200

tgcagcaagc ggtccacgct ggtttgcccc agcaggcgaa aatcctgttt gatggtggtt   1260

gacggcggga tataacatga gctgtcttcg gtatcgtcgt atcccactac cgagatatcc   1320

gcaccaacgc gcagcccgga ctcggtaatg gcgcgcattg cgcccagcgc catctgatcg   1380

ttggcaacca gcatcgcagt gggaacgatg ccctcattca gcatttgcat ggtttgttga   1440

aaaccggaca tggcactcca gtcgccttcc cgttccgcta tcggctgaat ttgattgcga   1500

gtgagatatt tatgccagcc agccagacgc agacgcgccg agacagaact taatgggccc   1560

gctaacagcg cgatttgctg gtgacccaat gcgaccagat gctccacgcc cagtcgcgta   1620

ccgtcttcat gggagaaaat aatactgttg atgggtgtct ggtcagagac atcaagaaat   1680

aacgccggaa cattagtgca ggcagcttcc acagcaatgg catcctggtc atccagcgga   1740

tagttaatga tcagcccact gacgcgttgc gcgagaagat tgtgcaccgc cgctttacag   1800

gcttcgacgc cgcttcgttc taccatcgac accaccacgc tggcacccag ttgatcggcg   1860

cgagatttaa tcgccgcgac aatttgcgac ggcgcgtgca gggccagact ggaggtggca   1920

acgccaatca gcaacgactg tttgcccgcc agttgttgtg ccacgcggtt gggaatgtaa   1980

ttcagctccg ccatcgccgc ttccactttt tcccgcgttt tcgcagaaac gtggctggcc   2040

tggttcacca cgcgggaaac ggtctgataa gagacaccgg catactctgc gacatcgtat   2100

aacgttactg gtttcacatt caccaccctg aattgactct cttccgggcg ctatcatgcc   2160

ataccgcgaa aggttttgca ccattcgatg gtgtcgggta ccgagctcga atttacgtga   2220

accatcaccc aaatcaagtt ttttgcggtc gaggtgccgt aaagctctaa atcggaaccc   2280

taaagggagc ccccgattta gagcttgacg gggaaagccg gcgaacgtgg cgagaaagga   2340

agggaagaaa gcgaaaggag cgggcgctag ggcgctggca agtgtagcgg tcacgctgcg   2400

cgtaaccacc acacccgccg cgcttaatgc gccgctacag ggcgcgtcgc ctgatgcggt   2460

attttctcct tacgcatctg tgcggtattt cacaccgcat atggtgcact ctcagtacaa   2520

tctgctctga tgccgcatag ttaagccagc cccgacaccc gccaacaccc gctgacgcgc   2580

cctgacgggc ttgtctgctc ccggcatccg cttacagaca agctgtgacc gtctccggga   2640

gctgcatgtg tcagaggttt tcaccgtcat caccgaaacg cgcgagacga aagggcctcg   2700

tgatacgcct atttttatag gttaatgtca tgataataat ggtttcttag acgtcaggtg   2760

gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa atacattcaa   2820

atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat tgaaaaagga   2880

agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg gcattttgcc   2940

ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg   3000

gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt gagagttttc   3060

gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt catacactat   3120

tatcccgtat tgacgccggg caagagcaac tcggtcgccg ggcgcggtat tctcagaatg   3180

acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg acagtaagag   3240

aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta cttctgacaa   3300

cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat catgtaactc   3360

gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag cgtgacacca   3420

cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa ctacttactc   3480

tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca ggaccacttc   3540

tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc ggtgagcgtg   3600

ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt atcgtagtta   3660

tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc gctgagatag   3720

gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat atactttaga   3780

ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt tttgataatc   3840

tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac cccgtagaaa   3900

agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa   3960

aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc   4020

cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta gtgtagccgt   4080

agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc   4140

tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac   4200

gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca   4260

gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg   4320

ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag   4380

gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt cctgtcgggt   4440

ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg cggagcctat   4500

ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg ccttttgctc   4560

acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc gcctttgagt   4620

gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg agcgaggaag   4680

cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt cattaatgca   4740

gctgat                                                              4746


<210>  10
<211>  4746
<212>  DNA
<213>  artificial

<220>
<223>  pHAT2/FGFR1 mutant

<400>  10
taatacgact cactataggg aattgtgagc ggataacaat tcctctagaa ataattttgt     60

ttaactttaa gaaggagata tatccatgag tcatcaccat caccatcact ccatggggac    120

caaaccaaac cgtatgcccg tagctccata ttggacatcc ccagaaaaga tggaaaagaa    180

attgcatgca gtgccggctg ccaagacagt gaagttcaaa tgcccttcca gtgggacccc    240

aaaccccaca ctgcgctggt tgaaaaatgg caaagaattc aaacctgacc acagaattgg    300

aggctacaag gtccgtaaag ccacctggag catcataatg aaatctgtgg tgccctctga    360

caagggcaac tacacctgca ttgtggagaa tgagtacggc agcatcaacc acacatacca    420

gctggatgtc gtgtaactcg agggatccgg gccctctaga tgcggccgca tgcataagct    480

tgagtattct atagtgtcac ctaaatccca gcttgatccg gctgctaaca aagcccgaaa    540

ggaagctgag ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc    600

taaacgggtc ttgaggggtt ttttgctgaa aggaggaact atatccggat aacctggcgt    660

aatagcgaag aggcccgcac cgatcgccct tcccaacagt tgcgcagcct gaatggcgaa    720

tggaaattgt aaacgttaat attttgttaa aattcgcgtt aaatatttgt taaatcagct    780

cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg    840

agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact    900

ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacag cttgcatgcc    960

tgcaggtcgg aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat   1020

taattgcgtt gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt   1080

aatgaatcgg ccaacgcgcg gggagaggcg gtttgcgtat tgggcgccag ggtggttttt   1140

cttttcacca gtgagacggg caacagctga ttgcccttca ccgcctggcc ctgagagagt   1200

tgcagcaagc ggtccacgct ggtttgcccc agcaggcgaa aatcctgttt gatggtggtt   1260

gacggcggga tataacatga gctgtcttcg gtatcgtcgt atcccactac cgagatatcc   1320

gcaccaacgc gcagcccgga ctcggtaatg gcgcgcattg cgcccagcgc catctgatcg   1380

ttggcaacca gcatcgcagt gggaacgatg ccctcattca gcatttgcat ggtttgttga   1440

aaaccggaca tggcactcca gtcgccttcc cgttccgcta tcggctgaat ttgattgcga   1500

gtgagatatt tatgccagcc agccagacgc agacgcgccg agacagaact taatgggccc   1560

gctaacagcg cgatttgctg gtgacccaat gcgaccagat gctccacgcc cagtcgcgta   1620

ccgtcttcat gggagaaaat aatactgttg atgggtgtct ggtcagagac atcaagaaat   1680

aacgccggaa cattagtgca ggcagcttcc acagcaatgg catcctggtc atccagcgga   1740

tagttaatga tcagcccact gacgcgttgc gcgagaagat tgtgcaccgc cgctttacag   1800

gcttcgacgc cgcttcgttc taccatcgac accaccacgc tggcacccag ttgatcggcg   1860

cgagatttaa tcgccgcgac aatttgcgac ggcgcgtgca gggccagact ggaggtggca   1920

acgccaatca gcaacgactg tttgcccgcc agttgttgtg ccacgcggtt gggaatgtaa   1980

ttcagctccg ccatcgccgc ttccactttt tcccgcgttt tcgcagaaac gtggctggcc   2040

tggttcacca cgcgggaaac ggtctgataa gagacaccgg catactctgc gacatcgtat   2100

aacgttactg gtttcacatt caccaccctg aattgactct cttccgggcg ctatcatgcc   2160

ataccgcgaa aggttttgca ccattcgatg gtgtcgggta ccgagctcga atttacgtga   2220

accatcaccc aaatcaagtt ttttgcggtc gaggtgccgt aaagctctaa atcggaaccc   2280

taaagggagc ccccgattta gagcttgacg gggaaagccg gcgaacgtgg cgagaaagga   2340

agggaagaaa gcgaaaggag cgggcgctag ggcgctggca agtgtagcgg tcacgctgcg   2400

cgtaaccacc acacccgccg cgcttaatgc gccgctacag ggcgcgtcgc ctgatgcggt   2460

attttctcct tacgcatctg tgcggtattt cacaccgcat atggtgcact ctcagtacaa   2520

tctgctctga tgccgcatag ttaagccagc cccgacaccc gccaacaccc gctgacgcgc   2580

cctgacgggc ttgtctgctc ccggcatccg cttacagaca agctgtgacc gtctccggga   2640

gctgcatgtg tcagaggttt tcaccgtcat caccgaaacg cgcgagacga aagggcctcg   2700

tgatacgcct atttttatag gttaatgtca tgataataat ggtttcttag acgtcaggtg   2760

gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa atacattcaa   2820

atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat tgaaaaagga   2880

agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg gcattttgcc   2940

ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg   3000

gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt gagagttttc   3060

gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt catacactat   3120

tatcccgtat tgacgccggg caagagcaac tcggtcgccg ggcgcggtat tctcagaatg   3180

acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg acagtaagag   3240

aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta cttctgacaa   3300

cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat catgtaactc   3360

gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag cgtgacacca   3420

cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa ctacttactc   3480

tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca ggaccacttc   3540

tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc ggtgagcgtg   3600

ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt atcgtagtta   3660

tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc gctgagatag   3720

gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat atactttaga   3780

ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt tttgataatc   3840

tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac cccgtagaaa   3900

agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa   3960

aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc   4020

cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta gtgtagccgt   4080

agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc   4140

tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac   4200

gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca   4260

gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg   4320

ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag   4380

gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt cctgtcgggt   4440

ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg cggagcctat   4500

ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg ccttttgctc   4560

acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc gcctttgagt   4620

gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg agcgaggaag   4680

cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt cattaatgca   4740

gctgat                                                              4746


<210>  11
<211>  4746
<212>  DNA
<213>  artificial

<220>
<223>  pHAT2/mutant FGFR 1

<400>  11
taatacgact cactataggg aattgtgagc ggataacaat tcctctagaa ataattttgt     60

ttaactttaa gaaggagata tatccatgag tcatcaccat caccatcact ccatggggac    120

caaaccaaac cgtatgcccg tagctccata ttggacatcc ccagaaaaga tggaaaagaa    180

attgcatgca gtgccggctg ccaagacagt gaagttcaaa tgcccttcca gtgggacccc    240

aaaccccaca ctgcgctggt tgaaaaatgg caaagaattc aaacctgacc acagaattgg    300

aggctacaag gtccgttatg ccacctggag catcaaaatg aaatctgtgg tgccctctga    360

caagggcaac tacacctgca ttgtggagaa tgagtacggc agcatcaacc acacatacca    420

gctggatgtc gtgtaactcg agggatccgg gccctctaga tgcggccgca tgcataagct    480

tgagtattct atagtgtcac ctaaatccca gcttgatccg gctgctaaca aagcccgaaa    540

ggaagctgag ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc    600

taaacgggtc ttgaggggtt ttttgctgaa aggaggaact atatccggat aacctggcgt    660

aatagcgaag aggcccgcac cgatcgccct tcccaacagt tgcgcagcct gaatggcgaa    720

tggaaattgt aaacgttaat attttgttaa aattcgcgtt aaatatttgt taaatcagct    780

cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg    840

agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact    900

ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacag cttgcatgcc    960

tgcaggtcgg aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat   1020

taattgcgtt gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt   1080

aatgaatcgg ccaacgcgcg gggagaggcg gtttgcgtat tgggcgccag ggtggttttt   1140

cttttcacca gtgagacggg caacagctga ttgcccttca ccgcctggcc ctgagagagt   1200

tgcagcaagc ggtccacgct ggtttgcccc agcaggcgaa aatcctgttt gatggtggtt   1260

gacggcggga tataacatga gctgtcttcg gtatcgtcgt atcccactac cgagatatcc   1320

gcaccaacgc gcagcccgga ctcggtaatg gcgcgcattg cgcccagcgc catctgatcg   1380

ttggcaacca gcatcgcagt gggaacgatg ccctcattca gcatttgcat ggtttgttga   1440

aaaccggaca tggcactcca gtcgccttcc cgttccgcta tcggctgaat ttgattgcga   1500

gtgagatatt tatgccagcc agccagacgc agacgcgccg agacagaact taatgggccc   1560

gctaacagcg cgatttgctg gtgacccaat gcgaccagat gctccacgcc cagtcgcgta   1620

ccgtcttcat gggagaaaat aatactgttg atgggtgtct ggtcagagac atcaagaaat   1680

aacgccggaa cattagtgca ggcagcttcc acagcaatgg catcctggtc atccagcgga   1740

tagttaatga tcagcccact gacgcgttgc gcgagaagat tgtgcaccgc cgctttacag   1800

gcttcgacgc cgcttcgttc taccatcgac accaccacgc tggcacccag ttgatcggcg   1860

cgagatttaa tcgccgcgac aatttgcgac ggcgcgtgca gggccagact ggaggtggca   1920

acgccaatca gcaacgactg tttgcccgcc agttgttgtg ccacgcggtt gggaatgtaa   1980

ttcagctccg ccatcgccgc ttccactttt tcccgcgttt tcgcagaaac gtggctggcc   2040

tggttcacca cgcgggaaac ggtctgataa gagacaccgg catactctgc gacatcgtat   2100

aacgttactg gtttcacatt caccaccctg aattgactct cttccgggcg ctatcatgcc   2160

ataccgcgaa aggttttgca ccattcgatg gtgtcgggta ccgagctcga atttacgtga   2220

accatcaccc aaatcaagtt ttttgcggtc gaggtgccgt aaagctctaa atcggaaccc   2280

taaagggagc ccccgattta gagcttgacg gggaaagccg gcgaacgtgg cgagaaagga   2340

agggaagaaa gcgaaaggag cgggcgctag ggcgctggca agtgtagcgg tcacgctgcg   2400

cgtaaccacc acacccgccg cgcttaatgc gccgctacag ggcgcgtcgc ctgatgcggt   2460

attttctcct tacgcatctg tgcggtattt cacaccgcat atggtgcact ctcagtacaa   2520

tctgctctga tgccgcatag ttaagccagc cccgacaccc gccaacaccc gctgacgcgc   2580

cctgacgggc ttgtctgctc ccggcatccg cttacagaca agctgtgacc gtctccggga   2640

gctgcatgtg tcagaggttt tcaccgtcat caccgaaacg cgcgagacga aagggcctcg   2700

tgatacgcct atttttatag gttaatgtca tgataataat ggtttcttag acgtcaggtg   2760

gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa atacattcaa   2820

atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat tgaaaaagga   2880

agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg gcattttgcc   2940

ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg   3000

gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt gagagttttc   3060

gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt catacactat   3120

tatcccgtat tgacgccggg caagagcaac tcggtcgccg ggcgcggtat tctcagaatg   3180

acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg acagtaagag   3240

aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta cttctgacaa   3300

cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat catgtaactc   3360

gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag cgtgacacca   3420

cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa ctacttactc   3480

tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca ggaccacttc   3540

tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc ggtgagcgtg   3600

ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt atcgtagtta   3660

tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc gctgagatag   3720

gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat atactttaga   3780

ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt tttgataatc   3840

tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac cccgtagaaa   3900

agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa   3960

aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc   4020

cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta gtgtagccgt   4080

agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc   4140

tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac   4200

gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca   4260

gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg   4320

ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag   4380

gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt cctgtcgggt   4440

ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg cggagcctat   4500

ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg ccttttgctc   4560

acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc gcctttgagt   4620

gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg agcgaggaag   4680

cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt cattaatgca   4740

gctgat                                                              4746


<210>  12
<211>  4746
<212>  DNA
<213>  artificial

<220>
<223>  pHAT2/mutant FGFR1

<400>  12
taatacgact cactataggg aattgtgagc ggataacaat tcctctagaa ataattttgt     60

ttaactttaa gaaggagata tatccatgag tcatcaccat caccatcact ccatggggac    120

caaaccaaac cgtatgcccg tagctccata ttggacatcc ccagaaaaga tggaaaagaa    180

attgcatgca gtgccggctg ccaagacagt gaagttcaaa tgcccttcca gtgggacccc    240

aaaccccaca ctgcgctggt tgaaaaatgg caaagaattc aaacctgacc acagaattgg    300

aggctacaag gtccgtaaag ccacctggag catcaaaatg aaatctgtgg tgccctctga    360

caagggcaac tacacctgca ttgtggagaa tgagtacggc agcatcaacc acacatacca    420

gctggatgtc gtgtaactcg agggatccgg gccctctaga tgcggccgca tgcataagct    480

tgagtattct atagtgtcac ctaaatccca gcttgatccg gctgctaaca aagcccgaaa    540

ggaagctgag ttggctgctg ccaccgctga gcaataacta gcataacccc ttggggcctc    600

taaacgggtc ttgaggggtt ttttgctgaa aggaggaact atatccggat aacctggcgt    660

aatagcgaag aggcccgcac cgatcgccct tcccaacagt tgcgcagcct gaatggcgaa    720

tggaaattgt aaacgttaat attttgttaa aattcgcgtt aaatatttgt taaatcagct    780

cattttttaa ccaataggcc gaaatcggca aaatccctta taaatcaaaa gaatagaccg    840

agatagggtt gagtgttgtt ccagtttgga acaagagtcc actattaaag aacgtggact    900

ccaacgtcaa agggcgaaaa accgtctatc agggcgatgg cccactacag cttgcatgcc    960

tgcaggtcgg aagcataaag tgtaaagcct ggggtgccta atgagtgagc taactcacat   1020

taattgcgtt gcgctcactg cccgctttcc agtcgggaaa cctgtcgtgc cagctgcatt   1080

aatgaatcgg ccaacgcgcg gggagaggcg gtttgcgtat tgggcgccag ggtggttttt   1140

cttttcacca gtgagacggg caacagctga ttgcccttca ccgcctggcc ctgagagagt   1200

tgcagcaagc ggtccacgct ggtttgcccc agcaggcgaa aatcctgttt gatggtggtt   1260

gacggcggga tataacatga gctgtcttcg gtatcgtcgt atcccactac cgagatatcc   1320

gcaccaacgc gcagcccgga ctcggtaatg gcgcgcattg cgcccagcgc catctgatcg   1380

ttggcaacca gcatcgcagt gggaacgatg ccctcattca gcatttgcat ggtttgttga   1440

aaaccggaca tggcactcca gtcgccttcc cgttccgcta tcggctgaat ttgattgcga   1500

gtgagatatt tatgccagcc agccagacgc agacgcgccg agacagaact taatgggccc   1560

gctaacagcg cgatttgctg gtgacccaat gcgaccagat gctccacgcc cagtcgcgta   1620

ccgtcttcat gggagaaaat aatactgttg atgggtgtct ggtcagagac atcaagaaat   1680

aacgccggaa cattagtgca ggcagcttcc acagcaatgg catcctggtc atccagcgga   1740

tagttaatga tcagcccact gacgcgttgc gcgagaagat tgtgcaccgc cgctttacag   1800

gcttcgacgc cgcttcgttc taccatcgac accaccacgc tggcacccag ttgatcggcg   1860

cgagatttaa tcgccgcgac aatttgcgac ggcgcgtgca gggccagact ggaggtggca   1920

acgccaatca gcaacgactg tttgcccgcc agttgttgtg ccacgcggtt gggaatgtaa   1980

ttcagctccg ccatcgccgc ttccactttt tcccgcgttt tcgcagaaac gtggctggcc   2040

tggttcacca cgcgggaaac ggtctgataa gagacaccgg catactctgc gacatcgtat   2100

aacgttactg gtttcacatt caccaccctg aattgactct cttccgggcg ctatcatgcc   2160

ataccgcgaa aggttttgca ccattcgatg gtgtcgggta ccgagctcga atttacgtga   2220

accatcaccc aaatcaagtt ttttgcggtc gaggtgccgt aaagctctaa atcggaaccc   2280

taaagggagc ccccgattta gagcttgacg gggaaagccg gcgaacgtgg cgagaaagga   2340

agggaagaaa gcgaaaggag cgggcgctag ggcgctggca agtgtagcgg tcacgctgcg   2400

cgtaaccacc acacccgccg cgcttaatgc gccgctacag ggcgcgtcgc ctgatgcggt   2460

attttctcct tacgcatctg tgcggtattt cacaccgcat atggtgcact ctcagtacaa   2520

tctgctctga tgccgcatag ttaagccagc cccgacaccc gccaacaccc gctgacgcgc   2580

cctgacgggc ttgtctgctc ccggcatccg cttacagaca agctgtgacc gtctccggga   2640

gctgcatgtg tcagaggttt tcaccgtcat caccgaaacg cgcgagacga aagggcctcg   2700

tgatacgcct atttttatag gttaatgtca tgataataat ggtttcttag acgtcaggtg   2760

gcacttttcg gggaaatgtg cgcggaaccc ctatttgttt atttttctaa atacattcaa   2820

atatgtatcc gctcatgaga caataaccct gataaatgct tcaataatat tgaaaaagga   2880

agagtatgag tattcaacat ttccgtgtcg cccttattcc cttttttgcg gcattttgcc   2940

ttcctgtttt tgctcaccca gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg   3000

gtgcacgagt gggttacatc gaactggatc tcaacagcgg taagatcctt gagagttttc   3060

gccccgaaga acgttttcca atgatgagca cttttaaagt tctgctatgt catacactat   3120

tatcccgtat tgacgccggg caagagcaac tcggtcgccg ggcgcggtat tctcagaatg   3180

acttggttga gtactcacca gtcacagaaa agcatcttac ggatggcatg acagtaagag   3240

aattatgcag tgctgccata accatgagtg ataacactgc ggccaactta cttctgacaa   3300

cgatcggagg accgaaggag ctaaccgctt ttttgcacaa catgggggat catgtaactc   3360

gccttgatcg ttgggaaccg gagctgaatg aagccatacc aaacgacgag cgtgacacca   3420

cgatgcctgt agcaatggca acaacgttgc gcaaactatt aactggcgaa ctacttactc   3480

tagcttcccg gcaacaatta atagactgga tggaggcgga taaagttgca ggaccacttc   3540

tgcgctcggc ccttccggct ggctggttta ttgctgataa atctggagcc ggtgagcgtg   3600

ggtctcgcgg tatcattgca gcactggggc cagatggtaa gccctcccgt atcgtagtta   3660

tctacacgac ggggagtcag gcaactatgg atgaacgaaa tagacagatc gctgagatag   3720

gtgcctcact gattaagcat tggtaactgt cagaccaagt ttactcatat atactttaga   3780

ttgatttaaa acttcatttt taatttaaaa ggatctaggt gaagatcctt tttgataatc   3840

tcatgaccaa aatcccttaa cgtgagtttt cgttccactg agcgtcagac cccgtagaaa   3900

agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa   3960

aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc   4020

cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta gtgtagccgt   4080

agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc   4140

tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac   4200

gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca   4260

gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg   4320

ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag   4380

gagagcgcac gagggagctt ccagggggaa acgcctggta tctttatagt cctgtcgggt   4440

ttcgccacct ctgacttgag cgtcgatttt tgtgatgctc gtcagggggg cggagcctat   4500

ggaaaaacgc cagcaacgcg gcctttttac ggttcctggc cttttgctgg ccttttgctc   4560

acatgttctt tcctgcgtta tcccctgatt ctgtggataa ccgtattacc gcctttgagt   4620

gagctgatac cgctcgccgc agccgaacga ccgagcgcag cgagtcagtg agcgaggaag   4680

cggaagagcg cccaatacgc aaaccgcctc tccccgcgcg ttggccgatt cattaatgca   4740

gctgat                                                              4746


<210>  13
<211>  105
<212>  PRT
<213>  artificial

<220>
<223>  mutant FGFR1


<220>
<221>  misc_feature
<222>  (17)..(17)
<223>  Xaa is His, Lys or Arg

<220>
<221>  misc_feature
<222>  (20)..(20)
<223>  Xaa is His, Lys or Arg

<220>
<221>  misc_feature
<222>  (29)..(29)
<223>  Xaa is His, Lys or Arg

<220>
<221>  misc_feature
<222>  (32)..(32)
<223>  Xaa is His, Lys or Arg

<220>
<221>  misc_feature
<222>  (34)..(34)
<223>  Xaa is His, Lys or Arg

<220>
<221>  misc_feature
<222>  (67)..(67)
<223>  Xaa is Tyr, His, Lys or Arg

<220>
<221>  misc_feature
<222>  (73)..(73)
<223>  Xaa is Ile, His, Lys or Arg

<220>
<221>  misc_feature
<222>  (75)..(75)
<223>  Xaa is Asx,  His, Lys or Arg

<400>  13

Thr Lys Pro Asn Arg Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu 
1               5                   10                  15      


Xaa Met Glu Xaa Lys Leu His Ala Val Pro Ala Ala Xaa Thr Val Xaa 
            20                  25                  30          


Phe Xaa Cys Pro Ser Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu 
        35                  40                  45              


Lys Asn Gly Lys Glu Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys 
    50                  55                  60                  


Val Arg Xaa Ala Thr Trp Ser Ile Xaa Met Xaa Ser Val Val Pro Ser 
65                  70                  75                  80  


Asp Lys Gly Asn Tyr Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile 
                85                  90                  95      


Asn His Thr Tyr Gln Leu Asp Val Val 
            100                 105 


<210>  14
<211>  221
<212>  PRT
<213>  artificial

<220>
<223>  mutant FGFR1


<220>
<221>  misc_feature
<222>  (17)..(17)
<223>  Xaa is Arg, Lys, His

<220>
<221>  misc_feature
<222>  (20)..(20)
<223>  Xaa is Arg, Lys, His

<220>
<221>  misc_feature
<222>  (29)..(29)
<223>  Xaa is Arg, Lys, His

<220>
<221>  misc_feature
<222>  (32)..(32)
<223>  Xaa is Arg, Lys, His

<220>
<221>  misc_feature
<222>  (34)..(34)
<223>  Xaa is Arg, Lys, His

<220>
<221>  misc_feature
<222>  (67)..(67)
<223>  Xaa is Tyr,  Arg, Lys, His

<220>
<221>  misc_feature
<222>  (73)..(73)
<223>  Xaa is Ile, Arg, Lys, His

<220>
<221>  misc_feature
<222>  (75)..(75)
<223>  Xaa is Asx, Arg, Lys, His

<400>  14

Thr Lys Pro Asn Arg Met Pro Val Ala Pro Tyr Trp Thr Ser Pro Glu 
1               5                   10                  15      


Xaa Met Glu Xaa Lys Leu His Ala Val Pro Ala Ala Xaa Thr Val Xaa 
            20                  25                  30          


Phe Xaa Cys Pro Ser Ser Gly Thr Pro Asn Pro Thr Leu Arg Trp Leu 
        35                  40                  45              


Lys Asn Gly Lys Glu Phe Lys Pro Asp His Arg Ile Gly Gly Tyr Lys 
    50                  55                  60                  


Val Arg Xaa Ala Thr Trp Ser Ile Xaa Met Xaa Ser Val Val Pro Ser 
65                  70                  75                  80  


Asp Lys Gly Asn Tyr Thr Cys Ile Val Glu Asn Glu Tyr Gly Ser Ile 
                85                  90                  95      


Asn His Thr Tyr Gln Leu Asp Val Val Glu Arg Ser Pro His Arg Pro 
            100                 105                 110         


Ile Leu Gln Ala Gly Leu Pro Ala Asn Lys Thr Val Ala Leu Gly Ser 
        115                 120                 125             


Asn Val Glu Phe Met Cys Lys Val Tyr Ser Asp Pro Gln Pro His Ile 
    130                 135                 140                 


Gln Trp Leu Lys His Ile Glu Val Asn Gly Ser Lys Ile Gly Pro Asp 
145                 150                 155                 160 


Asn Leu Pro Tyr Val Gln Ile Leu Lys Thr Ala Gly Val Asn Thr Thr 
                165                 170                 175     


Asp Lys Glu Met Glu Val Leu His Leu Arg Asn Val Ser Phe Glu Asp 
            180                 185                 190         


Ala Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Leu Ser His 
        195                 200                 205             


His Ser Ala Trp Leu Thr Val Leu Glu Ala Leu Glu Glu 
    210                 215                 220     


<210>  15
<211>  351
<212>  DNA
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  15
atgagtcatc accatcacca tcactccatg gggaccaaac caaaccgtat gcccgtagct     60

ccatattgga catccccaga aaagatggaa aagaaattgc atgcagtgcc ggctgccaag    120

acagtgaagt tcaaatgccc ttccagtggg accccaaacc ccacactgcg ctggttgaaa    180

aatggcaaag aattcaaacc tgaccacaga attggaggct acaaggtccg taaagccacc    240

tggagcatca aaatggactc tgtggtgccc tctgacaagg gcaactacac ctgcattgtg    300

gagaatgagt acggcagcat caaccacaca taccagctgg atgtcgtgta a             351


<210>  16
<211>  351
<212>  DNA
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  16
atgagtcatc accatcacca tcactccatg gggaccaaac caaaccgtat gcccgtagct     60

ccatattgga catccccaga aaagatggaa aagaaattgc atgcagtgcc ggctgccaag    120

acagtgaagt tcaaatgccc ttccagtggg accccaaacc ccacactgcg ctggttgaaa    180

aatggcaaag aattcaaacc tgaccacaga attggaggct acaaggtccg taaagccacc    240

tggagcatca taatgaaatc tgtggtgccc tctgacaagg gcaactacac ctgcattgtg    300

gagaatgagt acggcagcat caaccacaca taccagctgg atgtcgtgta a             351


<210>  17
<211>  351
<212>  DNA
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  17
atgagtcatc accatcacca tcactccatg gggaccaaac caaaccgtat gcccgtagct     60

ccatattgga catccccaga aaagatggaa aagaaattgc atgcagtgcc ggctgccaag    120

acagtgaagt tcaaatgccc ttccagtggg accccaaacc ccacactgcg ctggttgaaa    180

aatggcaaag aattcaaacc tgaccacaga attggaggct acaaggtccg ttatgccacc    240

tggagcatca aaatgaaatc tgtggtgccc tctgacaagg gcaactacac ctgcattgtg    300

gagaatgagt acggcagcat caaccacaca taccagctgg atgtcgtgta a             351


<210>  18
<211>  351
<212>  DNA
<213>  artificial

<220>
<223>  mutant FGFR1

<400>  18
atgagtcatc accatcacca tcactccatg gggaccaaac caaaccgtat gcccgtagct     60

ccatattgga catccccaga aaagatggaa aagaaattgc atgcagtgcc ggctgccaag    120

acagtgaagt tcaaatgccc ttccagtggg accccaaacc ccacactgcg ctggttgaaa    180

aatggcaaag aattcaaacc tgaccacaga attggaggct acaaggtccg taaagccacc    240

tggagcatca aaatgaaatc tgtggtgccc tctgacaagg gcaactacac ctgcattgtg    300

gagaatgagt acggcagcat caaccacaca taccagctgg atgtcgtgta a             351


<210>  19
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  leader sequence

<400>  19

His His His His His His Ser Met Gly 
1               5                   


<210>  20
<211>  11
<212>  DNA
<213>  artificial

<220>
<223>  signal sequence

<400>  20
mshhhhhhsm g                                                          11


