                         SEQUENCE LISTING

<110>  Genentech, Inc.
       de Sauvage, Frederic J.
       Dijkgraaf, Gerrit J. P.
       Januario, Thomas
       Yauch, Robert L.
 
<120>  Mutant Smoothened and Methods of Using the Same

<130>  P4367R1 WO

<150>  61/239364
<151>  2009-09-02

<160>  15    

<170>  PatentIn version 3.5

<210>  1
<211>  787
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Ala Ala Arg Pro Ala Arg Gly Pro Glu Leu Pro Leu Leu Gly 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Asp Pro Gly Arg Gly Ala Ala Ser 
            20                  25                  30          


Ser Gly Asn Ala Thr Gly Pro Gly Pro Arg Ser Ala Gly Gly Ser Ala 
        35                  40                  45              


Arg Arg Ser Ala Ala Val Thr Gly Pro Pro Pro Pro Leu Ser His Cys 
    50                  55                  60                  


Gly Arg Ala Ala Pro Cys Glu Pro Leu Arg Tyr Asn Val Cys Leu Gly 
65                  70                  75                  80  


Ser Val Leu Pro Tyr Gly Ala Thr Ser Thr Leu Leu Ala Gly Asp Ser 
                85                  90                  95      


Asp Ser Gln Glu Glu Ala His Gly Lys Leu Val Leu Trp Ser Gly Leu 
            100                 105                 110         


Arg Asn Ala Pro Arg Cys Trp Ala Val Ile Gln Pro Leu Leu Cys Ala 
        115                 120                 125             


Val Tyr Met Pro Lys Cys Glu Asn Asp Arg Val Glu Leu Pro Ser Arg 
    130                 135                 140                 


Thr Leu Cys Gln Ala Thr Arg Gly Pro Cys Ala Ile Val Glu Arg Glu 
145                 150                 155                 160 


Arg Gly Trp Pro Asp Phe Leu Arg Cys Thr Pro Asp Arg Phe Pro Glu 
                165                 170                 175     


Gly Cys Thr Asn Glu Val Gln Asn Ile Lys Phe Asn Ser Ser Gly Gln 
            180                 185                 190         


Cys Glu Val Pro Leu Val Arg Thr Asp Asn Pro Lys Ser Trp Tyr Glu 
        195                 200                 205             


Asp Val Glu Gly Cys Gly Ile Gln Cys Gln Asn Pro Leu Phe Thr Glu 
    210                 215                 220                 


Ala Glu His Gln Asp Met His Ser Tyr Ile Ala Ala Phe Gly Ala Val 
225                 230                 235                 240 


Thr Gly Leu Cys Thr Leu Phe Thr Leu Ala Thr Phe Val Ala Asp Trp 
                245                 250                 255     


Arg Asn Ser Asn Arg Tyr Pro Ala Val Ile Leu Phe Tyr Val Asn Ala 
            260                 265                 270         


Cys Phe Phe Val Gly Ser Ile Gly Trp Leu Ala Gln Phe Met Asp Gly 
        275                 280                 285             


Ala Arg Arg Glu Ile Val Cys Arg Ala Asp Gly Thr Met Arg Leu Gly 
    290                 295                 300                 


Glu Pro Thr Ser Asn Glu Thr Leu Ser Cys Val Ile Ile Phe Val Ile 
305                 310                 315                 320 


Val Tyr Tyr Ala Leu Met Ala Gly Val Val Trp Phe Val Val Leu Thr 
                325                 330                 335     


Tyr Ala Trp His Thr Ser Phe Lys Ala Leu Gly Thr Thr Tyr Gln Pro 
            340                 345                 350         


Leu Ser Gly Lys Thr Ser Tyr Phe His Leu Leu Thr Trp Ser Leu Pro 
        355                 360                 365             


Phe Val Leu Thr Val Ala Ile Leu Ala Val Ala Gln Val Asp Gly Asp 
    370                 375                 380                 


Ser Val Ser Gly Ile Cys Phe Val Gly Tyr Lys Asn Tyr Arg Tyr Arg 
385                 390                 395                 400 


Ala Gly Phe Val Leu Ala Pro Ile Gly Leu Val Leu Ile Val Gly Gly 
                405                 410                 415     


Tyr Phe Leu Ile Arg Gly Val Met Thr Leu Phe Ser Ile Lys Ser Asn 
            420                 425                 430         


His Pro Gly Leu Leu Ser Glu Lys Ala Ala Ser Lys Ile Asn Glu Thr 
        435                 440                 445             


Met Leu Arg Leu Gly Ile Phe Gly Phe Leu Ala Phe Gly Phe Val Leu 
    450                 455                 460                 


Ile Thr Phe Ser Cys His Phe Tyr Asp Phe Phe Asn Gln Ala Glu Trp 
465                 470                 475                 480 


Glu Arg Ser Phe Arg Asp Tyr Val Leu Cys Gln Ala Asn Val Thr Ile 
                485                 490                 495     


Gly Leu Pro Thr Lys Gln Pro Ile Pro Asp Cys Glu Ile Lys Asn Arg 
            500                 505                 510         


Pro Ser Leu Leu Val Glu Lys Ile Asn Leu Phe Ala Met Phe Gly Thr 
        515                 520                 525             


Gly Ile Ala Met Ser Thr Trp Val Trp Thr Lys Ala Thr Leu Leu Ile 
    530                 535                 540                 


Trp Arg Arg Thr Trp Cys Arg Leu Thr Gly Gln Ser Asp Asp Glu Pro 
545                 550                 555                 560 


Lys Arg Ile Lys Lys Ser Lys Met Ile Ala Lys Ala Phe Ser Lys Arg 
                565                 570                 575     


His Glu Leu Leu Gln Asn Pro Gly Gln Glu Leu Ser Phe Ser Met His 
            580                 585                 590         


Thr Val Ser His Asp Gly Pro Val Ala Gly Leu Ala Phe Asp Leu Asn 
        595                 600                 605             


Glu Pro Ser Ala Asp Val Ser Ser Ala Trp Ala Gln His Val Thr Lys 
    610                 615                 620                 


Met Val Ala Arg Arg Gly Ala Ile Leu Pro Gln Asp Ile Ser Val Thr 
625                 630                 635                 640 


Pro Val Ala Thr Pro Val Pro Pro Glu Glu Gln Ala Asn Leu Trp Leu 
                645                 650                 655     


Val Glu Ala Glu Ile Ser Pro Glu Leu Gln Lys Arg Leu Gly Arg Lys 
            660                 665                 670         


Lys Lys Arg Arg Lys Arg Lys Lys Glu Val Cys Pro Leu Ala Pro Pro 
        675                 680                 685             


Pro Glu Leu His Pro Pro Ala Pro Ala Pro Ser Thr Ile Pro Arg Leu 
    690                 695                 700                 


Pro Gln Leu Pro Arg Gln Lys Cys Leu Val Ala Ala Gly Ala Trp Gly 
705                 710                 715                 720 


Ala Gly Asp Ser Cys Arg Gln Gly Ala Trp Thr Leu Val Ser Asn Pro 
                725                 730                 735     


Phe Cys Pro Glu Pro Ser Pro Pro Gln Asp Pro Phe Leu Pro Ser Ala 
            740                 745                 750         


Pro Ala Pro Val Ala Trp Ala His Gly Arg Arg Gln Gly Leu Gly Pro 
        755                 760                 765             


Ile His Ser Arg Thr Asn Leu Met Asp Thr Glu Leu Met Asp Ala Asp 
    770                 775                 780                 


Ser Asp Phe 
785         


<210>  2
<211>  787
<212>  PRT
<213>  Homo sapiens


<220>
<221>  MISC_FEATURE
<222>  (473)..(473)
<223>  Xaa is any amino acidother than D

<400>  2

Met Ala Ala Ala Arg Pro Ala Arg Gly Pro Glu Leu Pro Leu Leu Gly 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Gly Asp Pro Gly Arg Gly Ala Ala Ser 
            20                  25                  30          


Ser Gly Asn Ala Thr Gly Pro Gly Pro Arg Ser Ala Gly Gly Ser Ala 
        35                  40                  45              


Arg Arg Ser Ala Ala Val Thr Gly Pro Pro Pro Pro Leu Ser His Cys 
    50                  55                  60                  


Gly Arg Ala Ala Pro Cys Glu Pro Leu Arg Tyr Asn Val Cys Leu Gly 
65                  70                  75                  80  


Ser Val Leu Pro Tyr Gly Ala Thr Ser Thr Leu Leu Ala Gly Asp Ser 
                85                  90                  95      


Asp Ser Gln Glu Glu Ala His Gly Lys Leu Val Leu Trp Ser Gly Leu 
            100                 105                 110         


Arg Asn Ala Pro Arg Cys Trp Ala Val Ile Gln Pro Leu Leu Cys Ala 
        115                 120                 125             


Val Tyr Met Pro Lys Cys Glu Asn Asp Arg Val Glu Leu Pro Ser Arg 
    130                 135                 140                 


Thr Leu Cys Gln Ala Thr Arg Gly Pro Cys Ala Ile Val Glu Arg Glu 
145                 150                 155                 160 


Arg Gly Trp Pro Asp Phe Leu Arg Cys Thr Pro Asp Arg Phe Pro Glu 
                165                 170                 175     


Gly Cys Thr Asn Glu Val Gln Asn Ile Lys Phe Asn Ser Ser Gly Gln 
            180                 185                 190         


Cys Glu Val Pro Leu Val Arg Thr Asp Asn Pro Lys Ser Trp Tyr Glu 
        195                 200                 205             


Asp Val Glu Gly Cys Gly Ile Gln Cys Gln Asn Pro Leu Phe Thr Glu 
    210                 215                 220                 


Ala Glu His Gln Asp Met His Ser Tyr Ile Ala Ala Phe Gly Ala Val 
225                 230                 235                 240 


Thr Gly Leu Cys Thr Leu Phe Thr Leu Ala Thr Phe Val Ala Asp Trp 
                245                 250                 255     


Arg Asn Ser Asn Arg Tyr Pro Ala Val Ile Leu Phe Tyr Val Asn Ala 
            260                 265                 270         


Cys Phe Phe Val Gly Ser Ile Gly Trp Leu Ala Gln Phe Met Asp Gly 
        275                 280                 285             


Ala Arg Arg Glu Ile Val Cys Arg Ala Asp Gly Thr Met Arg Leu Gly 
    290                 295                 300                 


Glu Pro Thr Ser Asn Glu Thr Leu Ser Cys Val Ile Ile Phe Val Ile 
305                 310                 315                 320 


Val Tyr Tyr Ala Leu Met Ala Gly Val Val Trp Phe Val Val Leu Thr 
                325                 330                 335     


Tyr Ala Trp His Thr Ser Phe Lys Ala Leu Gly Thr Thr Tyr Gln Pro 
            340                 345                 350         


Leu Ser Gly Lys Thr Ser Tyr Phe His Leu Leu Thr Trp Ser Leu Pro 
        355                 360                 365             


Phe Val Leu Thr Val Ala Ile Leu Ala Val Ala Gln Val Asp Gly Asp 
    370                 375                 380                 


Ser Val Ser Gly Ile Cys Phe Val Gly Tyr Lys Asn Tyr Arg Tyr Arg 
385                 390                 395                 400 


Ala Gly Phe Val Leu Ala Pro Ile Gly Leu Val Leu Ile Val Gly Gly 
                405                 410                 415     


Tyr Phe Leu Ile Arg Gly Val Met Thr Leu Phe Ser Ile Lys Ser Asn 
            420                 425                 430         


His Pro Gly Leu Leu Ser Glu Lys Ala Ala Ser Lys Ile Asn Glu Thr 
        435                 440                 445             


Met Leu Arg Leu Gly Ile Phe Gly Phe Leu Ala Phe Gly Phe Val Leu 
    450                 455                 460                 


Ile Thr Phe Ser Cys His Phe Tyr Xaa Phe Phe Asn Gln Ala Glu Trp 
465                 470                 475                 480 


Glu Arg Ser Phe Arg Asp Tyr Val Leu Cys Gln Ala Asn Val Thr Ile 
                485                 490                 495     


Gly Leu Pro Thr Lys Gln Pro Ile Pro Asp Cys Glu Ile Lys Asn Arg 
            500                 505                 510         


Pro Ser Leu Leu Val Glu Lys Ile Asn Leu Phe Ala Met Phe Gly Thr 
        515                 520                 525             


Gly Ile Ala Met Ser Thr Trp Val Trp Thr Lys Ala Thr Leu Leu Ile 
    530                 535                 540                 


Trp Arg Arg Thr Trp Cys Arg Leu Thr Gly Gln Ser Asp Asp Glu Pro 
545                 550                 555                 560 


Lys Arg Ile Lys Lys Ser Lys Met Ile Ala Lys Ala Phe Ser Lys Arg 
                565                 570                 575     


His Glu Leu Leu Gln Asn Pro Gly Gln Glu Leu Ser Phe Ser Met His 
            580                 585                 590         


Thr Val Ser His Asp Gly Pro Val Ala Gly Leu Ala Phe Asp Leu Asn 
        595                 600                 605             


Glu Pro Ser Ala Asp Val Ser Ser Ala Trp Ala Gln His Val Thr Lys 
    610                 615                 620                 


Met Val Ala Arg Arg Gly Ala Ile Leu Pro Gln Asp Ile Ser Val Thr 
625                 630                 635                 640 


Pro Val Ala Thr Pro Val Pro Pro Glu Glu Gln Ala Asn Leu Trp Leu 
                645                 650                 655     


Val Glu Ala Glu Ile Ser Pro Glu Leu Gln Lys Arg Leu Gly Arg Lys 
            660                 665                 670         


Lys Lys Arg Arg Lys Arg Lys Lys Glu Val Cys Pro Leu Ala Pro Pro 
        675                 680                 685             


Pro Glu Leu His Pro Pro Ala Pro Ala Pro Ser Thr Ile Pro Arg Leu 
    690                 695                 700                 


Pro Gln Leu Pro Arg Gln Lys Cys Leu Val Ala Ala Gly Ala Trp Gly 
705                 710                 715                 720 


Ala Gly Asp Ser Cys Arg Gln Gly Ala Trp Thr Leu Val Ser Asn Pro 
                725                 730                 735     


Phe Cys Pro Glu Pro Ser Pro Pro Gln Asp Pro Phe Leu Pro Ser Ala 
            740                 745                 750         


Pro Ala Pro Val Ala Trp Ala His Gly Arg Arg Gln Gly Leu Gly Pro 
        755                 760                 765             


Ile His Ser Arg Thr Asn Leu Met Asp Thr Glu Leu Met Asp Ala Asp 
    770                 775                 780                 


Ser Asp Phe 
785         


<210>  3
<211>  2364
<212>  DNA
<213>  Homo sapiens

<400>  3
atggccgctg cccgcccagc gcgggggccg gagctcccgc tcctggggct gctgctgctg       60

ctgctgctgg gggacccggg ccggggggcg gcctcgagcg ggaacgcgac cgggcctggg      120

cctcggagcg cgggcgggag cgcgaggagg agcgcggcgg tgactggccc tccgccgccg      180

ctgagccact gcggccgggc tgccccctgc gagccgctgc gctacaacgt gtgcctgggc      240

tcggtgctgc cctacggggc cacctccaca ctgctggccg gagactcgga ctcccaggag      300

gaagcgcacg gcaagctcgt gctctggtcg ggcctccgga atgccccccg ctgctgggca      360

gtgatccagc ccctgctgtg tgccgtatac atgcccaagt gtgagaatga ccgggtggag      420

ctgcccagcc gtaccctctg ccaggccacc cgaggcccct gtgccatcgt ggagagggag      480

cggggctggc ctgacttcct gcgctgcact cctgaccgct tccctgaagg ctgcacgaat      540

gaggtgcaga acatcaagtt caacagttca ggccagtgcg aagtgccctt ggttcggaca      600

gacaacccca agagctggta cgaggacgtg gagggctgcg gcatccagtg ccagaacccg      660

ctcttcacag aggctgagca ccaggacatg cacagctaca tcgcggcctt cggggccgtc      720

acgggcctct gcacgctctt caccctggcc acattcgtgg ctgactggcg gaactcgaat      780

cgctaccctg ctgttattct cttctacgtc aatgcgtgct tctttgtggg cagcattggc      840

tggctggccc agttcatgga tggtgcccgc cgagagatcg tctgccgtgc agatggcacc      900

atgaggcttg gggagcccac ctccaatgag actctgtcct gcgtcatcat ctttgtcatc      960

gtgtactacg ccctgatggc tggtgtggtt tggtttgtgg tcctcaccta tgcctggcac     1020

acttccttca aagccctggg caccacctac cagcctctct cgggcaagac ctcctacttc     1080

cacctgctca cctggtcact cccctttgtc ctcactgtgg caatccttgc tgtggcgcag     1140

gtggatgggg actctgtgag tggcatttgt tttgtgggct acaagaacta ccgataccgt     1200

gcgggcttcg tgctggcccc aatcggcctg gtgctcatcg tgggaggcta cttcctcatc     1260

cgaggagtca tgactctgtt ctccatcaag agcaaccacc ccgggctgct gagtgagaag     1320

gctgccagca agatcaacga gaccatgctg cgcctgggca tttttggctt cctggccttt     1380

ggctttgtgc tcattacctt cagctgccac ttctacgact tcttcaacca ggctgagtgg     1440

gagcgcagct tccgggacta tgtgctatgt caggccaatg tgaccatcgg gctgcccacc     1500

aagcagccca tccctgactg tgagatcaag aatcgcccga gccttctggt ggagaagatc     1560

aacctgtttg ccatgtttgg aactggcatc gccatgagca cctgggtctg gaccaaggcc     1620

acgctgctca tctggaggcg tacctggtgc aggttgactg ggcagagtga cgatgagcca     1680

aagcggatca agaagagcaa gatgattgcc aaggccttct ctaagcggca cgagctcctg     1740

cagaacccag gccaggagct gtccttcagc atgcacactg tgtcccacga cgggcccgtg     1800

gcgggcttgg cctttgacct caatgagccc tcagctgatg tctcctctgc ctgggcccag     1860

catgtcacca agatggtggc tcggagagga gccatactgc cccaggatat ttctgtcacc     1920

cctgtggcaa ctccagtgcc cccagaggaa caagccaacc tgtggctggt tgaggcagag     1980

atctccccag agctgcagaa gcgcctgggc cggaagaaga agaggaggaa gaggaagaag     2040

gaggtgtgcc cgctggcgcc gccccctgag cttcaccccc ctgcccctgc ccccagtacc     2100

attcctcgac tgcctcagct gccccggcag aaatgcctgg tggctgcagg tgcctgggga     2160

gctggggact cttgccgaca gggagcgtgg accctggtct ccaacccatt ctgcccagag     2220

cccagtcccc ctcaggatcc atttctgccc agtgcaccgg cccccgtggc atgggctcat     2280

ggccgccgac agggcctggg gcctattcac tcccgcacca acctgatgga cacagaactc     2340

atggatgcag actcggactt ctga                                            2364


<210>  4
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  4
gcaggacatt ccacacagtt cttg                                              24


<210>  5
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  5
ataggtgctg ggatacaggc ttg                                               23


<210>  6
<211>  25
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  6
taccctgaca ccaatctcct caacg                                             25


<210>  7
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  7
ggaattccca tcttcccaac tcc                                               23


<210>  8
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  8
agatggctga gtgggtaaag g                                                 21


<210>  9
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  9
gtggaggtca gaggacaaac tt                                                22


<210>  10
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  10
agaaggtgac ctggatgaga                                                   20


<210>  11
<211>  22
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  11
tgatacatat ggcggtcaat ct                                                22


<210>  12
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Probe

<400>  12
cttctcagga gataccggga atccaag                                           27


<210>  13
<211>  17
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  13
tcagctgcca cttctac                                                      17


<210>  14
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  14
tcagctgcca cttctacg                                                     18


<210>  15
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Oligonucleotide Primer

<400>  15
tcagctgcca cttctacc                                                     18


