                         SEQUENCE LISTING

<110>  Salk Institute for Biological Studies
 
<120>  FGF21 TRUNCATIONS AND MUTANTS AND USES THEREOF

<130>  7158-93561-02

<150>  US 62/053,987
<151>  2014-09-23

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  939
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (151)..(777)

<400>  1
ctgtcagctg aggatccagc cgaaagagga gccaggcact caggccacct gagtctactc       60

acctggacaa ctggaatctg gcaccaattc taaaccactc agcttctccg agctcacacc      120

ccggagatca cctgaggacc cgagccattg atg gac tcg gac gag acc ggg ttc       174
                                 Met Asp Ser Asp Glu Thr Gly Phe          
                                 1               5                        

gag cac tca gga ctg tgg gtt tct gtg ctg gct ggt ctg ctg gga gcc        222
Glu His Ser Gly Leu Trp Val Ser Val Leu Ala Gly Leu Leu Gly Ala           
    10                  15                  20                            

tgc cag gca cac ccc atc cct gac tcc agt cct ctc ctg caa ttc ggg        270
Cys Gln Ala His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly           
25                  30                  35                  40            

ggc caa gtc cgg cag cgg tac ctc tac aca gat gat gcc cag cag aca        318
Gly Gln Val Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr           
                45                  50                  55                

gaa gcc cac ctg gag atc agg gag gat ggg acg gtg ggg ggc gct gct        366
Glu Ala His Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala           
            60                  65                  70                    

gac cag agc ccc gaa agt ctc ctg cag ctg aaa gcc ttg aag ccg gga        414
Asp Gln Ser Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly           
        75                  80                  85                        

gtt att caa atc ttg gga gtc aag aca tcc agg ttc ctg tgc cag cgg        462
Val Ile Gln Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg           
    90                  95                  100                           

cca gat ggg gcc ctg tat gga tcg ctc cac ttt gac cct gag gcc tgc        510
Pro Asp Gly Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys           
105                 110                 115                 120           

agc ttc cgg gag ctg ctt ctt gag gac gga tac aat gtt tac cag tcc        558
Ser Phe Arg Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser           
                125                 130                 135               

gaa gcc cac ggc ctc ccg ctg cac ctg cca ggg aac aag tcc cca cac        606
Glu Ala His Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His           
            140                 145                 150                   

cgg gac cct gca ccc cga gga cca gct cgc ttc ctg cca cta cca ggc        654
Arg Asp Pro Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly           
        155                 160                 165                       

ctg ccc ccc gca ctc ccg gag cca ccc gga atc ctg gcc ccc cag ccc        702
Leu Pro Pro Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro           
    170                 175                 180                           

ccc gat gtg ggc tcc tcg gac cct ctg agc atg gtg gga cct tcc cag        750
Pro Asp Val Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln           
185                 190                 195                 200           

ggc cga agc ccc agc tac gct tcc tga agccagaggc tgtttactat              797
Gly Arg Ser Pro Ser Tyr Ala Ser                                           
                205                                                       

gacatctcct ctttatttat taggttattt atcttattta tttttttatt tttcttactt      857

gagataataa agagttccag aggagaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      917

aaaaaaaaaa aaaaaaaaaa ag                                               939


<210>  2
<211>  208
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Asp Ser Asp Glu Thr Gly Phe Glu His Ser Gly Leu Trp Val Ser 
1               5                   10                  15      


Val Leu Ala Gly Leu Leu Gly Ala Cys Gln Ala His Pro Ile Pro Asp 
            20                  25                  30          


Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg Tyr Leu 
        35                  40                  45              


Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His Leu Glu Ile Arg Glu 
    50                  55                  60                  


Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser Pro Glu Ser Leu Leu 
65                  70                  75                  80  


Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly Val Lys 
                85                  90                  95      


Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly Ala Leu Tyr Gly Ser 
            100                 105                 110         


Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu Leu Glu 
        115                 120                 125             


Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro Leu His 
    130                 135                 140                 


Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro Ala Pro Arg Gly Pro 
145                 150                 155                 160 


Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro Ala Leu Pro Glu Pro 
                165                 170                 175     


Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val Gly Ser Ser Asp Pro 
            180                 185                 190         


Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser Pro Ser Tyr Ala Ser 
        195                 200                 205             


<210>  3
<211>  181
<212>  PRT
<213>  Homo sapiens

<400>  3

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
            100                 105                 110         


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  4
<211>  947
<212>  DNA
<213>  Mus musculus


<220>
<221>  CDS
<222>  (185)..(817)

<400>  4
agacagcctt agtgtcttct cagctgggga ttcaacacag gagaaacagc cattcacttt       60

gcctgagccc cagtctgaac ctgacccatc cctgctgggc accggagtca gaacacaatt      120

ccagctgcct tggctcctca gccgctcgct tgccaggggc tctcccgaac ggagcgcagc      180

cctg atg gaa tgg atg aga tct aga gtt ggg acc ctg gga ctg tgg gtc       229
     Met Glu Trp Met Arg Ser Arg Val Gly Thr Leu Gly Leu Trp Val          
     1               5                   10                  15           

cga ctg ctg ctg gct gtc ttc ctg ctg ggg gtc tac caa gca tac ccc        277
Arg Leu Leu Leu Ala Val Phe Leu Leu Gly Val Tyr Gln Ala Tyr Pro           
                20                  25                  30                

atc cct gac tcc agc ccc ctc ctc cag ttt ggg ggt caa gtc cgg cag        325
Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln           
            35                  40                  45                    

agg tac ctc tac aca gat gac gac caa gac act gaa gcc cac ctg gag        373
Arg Tyr Leu Tyr Thr Asp Asp Asp Gln Asp Thr Glu Ala His Leu Glu           
        50                  55                  60                        

atc agg gag gat gga aca gtg gta ggc gca gca cac cgc agt cca gaa        421
Ile Arg Glu Asp Gly Thr Val Val Gly Ala Ala His Arg Ser Pro Glu           
    65                  70                  75                            

agt ctc ctg gag ctc aaa gcc ttg aag cca ggg gtc att caa atc ctg        469
Ser Leu Leu Glu Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu           
80                  85                  90                  95            

ggt gtc aaa gcc tct agg ttt ctt tgc caa cag cca gat gga gct ctc        517
Gly Val Lys Ala Ser Arg Phe Leu Cys Gln Gln Pro Asp Gly Ala Leu           
                100                 105                 110               

tat gga tcg cct cac ttt gat cct gag gcc tgc agc ttc aga gaa ctg        565
Tyr Gly Ser Pro His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu           
            115                 120                 125                   

ctg ctg gag gac ggt tac aat gtg tac cag tct gaa gcc cat ggc ctg        613
Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu           
        130                 135                 140                       

ccc ctg cgt ctg cct cag aag gac tcc cca aac cag gat gca aca tcc        661
Pro Leu Arg Leu Pro Gln Lys Asp Ser Pro Asn Gln Asp Ala Thr Ser           
    145                 150                 155                           

tgg gga cct gtg cgc ttc ctg ccc atg cca ggc ctg ctc cac gag ccc        709
Trp Gly Pro Val Arg Phe Leu Pro Met Pro Gly Leu Leu His Glu Pro           
160                 165                 170                 175           

caa gac caa gca gga ttc ctg ccc cca gag ccc cca gat gtg ggc tcc        757
Gln Asp Gln Ala Gly Phe Leu Pro Pro Glu Pro Pro Asp Val Gly Ser           
                180                 185                 190               

tct gac ccc ctg agc atg gta gag cct tta cag ggc cga agc ccc agc        805
Ser Asp Pro Leu Ser Met Val Glu Pro Leu Gln Gly Arg Ser Pro Ser           
            195                 200                 205                   

tat gcg tcc tga ctcttcctga atctagggct gtttcttttt gggtttccac            857
Tyr Ala Ser                                                               
        210                                                               

ttatttatta cgggtattta tcttatttat ttattttagt ttttttttct tacttggaat      917

aataaagagt ctgaaagaaa aatgtgtgtt                                       947


<210>  5
<211>  210
<212>  PRT
<213>  Mus musculus

<400>  5

Met Glu Trp Met Arg Ser Arg Val Gly Thr Leu Gly Leu Trp Val Arg 
1               5                   10                  15      


Leu Leu Leu Ala Val Phe Leu Leu Gly Val Tyr Gln Ala Tyr Pro Ile 
            20                  25                  30          


Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val Arg Gln Arg 
        35                  40                  45              


Tyr Leu Tyr Thr Asp Asp Asp Gln Asp Thr Glu Ala His Leu Glu Ile 
    50                  55                  60                  


Arg Glu Asp Gly Thr Val Val Gly Ala Ala His Arg Ser Pro Glu Ser 
65                  70                  75                  80  


Leu Leu Glu Leu Lys Ala Leu Lys Pro Gly Val Ile Gln Ile Leu Gly 
                85                  90                  95      


Val Lys Ala Ser Arg Phe Leu Cys Gln Gln Pro Asp Gly Ala Leu Tyr 
            100                 105                 110         


Gly Ser Pro His Phe Asp Pro Glu Ala Cys Ser Phe Arg Glu Leu Leu 
        115                 120                 125             


Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His Gly Leu Pro 
    130                 135                 140                 


Leu Arg Leu Pro Gln Lys Asp Ser Pro Asn Gln Asp Ala Thr Ser Trp 
145                 150                 155                 160 


Gly Pro Val Arg Phe Leu Pro Met Pro Gly Leu Leu His Glu Pro Gln 
                165                 170                 175     


Asp Gln Ala Gly Phe Leu Pro Pro Glu Pro Pro Asp Val Gly Ser Ser 
            180                 185                 190         


Asp Pro Leu Ser Met Val Glu Pro Leu Gln Gly Arg Ser Pro Ser Tyr 
        195                 200                 205             


Ala Ser 
    210 


<210>  6
<211>  181
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mutated FGF21 (28-208aa)(RN)

<400>  6

His Pro Ile Pro Asp Ser Ser Pro Leu Leu Gln Phe Gly Gly Gln Val 
1               5                   10                  15      


Arg Gln Val Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
            20                  25                  30          


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
        35                  40                  45              


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
    50                  55                  60                  


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


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
                85                  90                  95      


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


Gly Leu Pro Leu His Leu Pro Gly Asn Lys Ser Pro His Arg Asp Pro 
        115                 120                 125             


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
    130                 135                 140                 


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
145                 150                 155                 160 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
                165                 170                 175     


Pro Ser Tyr Ala Ser 
            180     


<210>  7
<211>  165
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mutant FGF21deltaNT (28-208aa)

<400>  7

Arg Gln Arg Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
1               5                   10                  15      


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
            20                  25                  30          


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
        35                  40                  45              


Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
    50                  55                  60                  


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
65                  70                  75                  80  


Glu Leu Leu Leu Glu Asp Gly Tyr Asn Val Tyr Gln Ser Glu Ala His 
                85                  90                  95      


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


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
        115                 120                 125             


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
    130                 135                 140                 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
145                 150                 155                 160 


Pro Ser Tyr Ala Ser 
                165 


<210>  8
<211>  165
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  mutated FGF21deltaNT (28-208 aa) (RN)

<400>  8

Arg Gln Val Tyr Leu Tyr Thr Asp Asp Ala Gln Gln Thr Glu Ala His 
1               5                   10                  15      


Leu Glu Ile Arg Glu Asp Gly Thr Val Gly Gly Ala Ala Asp Gln Ser 
            20                  25                  30          


Pro Glu Ser Leu Leu Gln Leu Lys Ala Leu Lys Pro Gly Val Ile Gln 
        35                  40                  45              


Ile Leu Gly Val Lys Thr Ser Arg Phe Leu Cys Gln Arg Pro Asp Gly 
    50                  55                  60                  


Ala Leu Tyr Gly Ser Leu His Phe Asp Pro Glu Ala Cys Ser Phe Arg 
65                  70                  75                  80  


Glu Leu Leu Leu Glu Asp Gly Tyr Val Val Tyr Gln Ser Glu Ala His 
                85                  90                  95      


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


Ala Pro Arg Gly Pro Ala Arg Phe Leu Pro Leu Pro Gly Leu Pro Pro 
        115                 120                 125             


Ala Leu Pro Glu Pro Pro Gly Ile Leu Ala Pro Gln Pro Pro Asp Val 
    130                 135                 140                 


Gly Ser Ser Asp Pro Leu Ser Met Val Gly Pro Ser Gln Gly Arg Ser 
145                 150                 155                 160 


Pro Ser Tyr Ala Ser 
                165 


<210>  9
<211>  140
<212>  PRT
<213>  Homo sapiens

<400>  9

Phe Asn Leu Pro Pro Gly Asn Tyr Lys Lys Pro Lys Leu Leu Tyr Cys 
1               5                   10                  15      


Ser Asn Gly Gly His Phe Leu Arg Ile Leu Pro Asp Gly Thr Val Asp 
            20                  25                  30          


Gly Thr Arg Asp Arg Ser Asp Gln His Ile Gln Leu Gln Leu Ser Ala 
        35                  40                  45              


Glu Ser Val Gly Glu Val Tyr Ile Lys Ser Thr Glu Thr Gly Gln Tyr 
    50                  55                  60                  


Leu Ala Met Asp Thr Asp Gly Leu Leu Tyr Gly Ser Gln Thr Pro Asn 
65                  70                  75                  80  


Glu Glu Cys Leu Phe Leu Glu Arg Leu Glu Glu Asn His Tyr Asn Thr 
                85                  90                  95      


Tyr Ile Ser Lys Lys His Ala Glu Lys Asn Trp Phe Val Gly Leu Lys 
            100                 105                 110         


Lys Asn Gly Ser Cys Lys Arg Gly Pro Arg Thr His Tyr Gly Gln Lys 
        115                 120                 125             


Ala Ile Leu Phe Leu Pro Leu Pro Val Ser Ser Asp 
    130                 135                 140 


<210>  10
<211>  145
<212>  PRT
<213>  Homo sapiens

<400>  10

Pro Ala Leu Pro Glu Asp Gly Gly Ala Ala Phe Pro Pro Gly His Phe 
1               5                   10                  15      


Lys Asp Pro Lys Arg Leu Tyr Cys Lys Asn Gly Gly Phe Phe Leu Arg 
            20                  25                  30          


Ile His Pro Asp Gly Arg Val Asp Gly Val Arg Glu Lys Ser Asp Pro 
        35                  40                  45              


His Val Lys Leu Gln Leu Gln Ala Glu Glu Arg Gly Val Val Ser Ile 
    50                  55                  60                  


Lys Gly Val Cys Ala Asn Arg Tyr Leu Ala Met Lys Glu Asp Gly Arg 
65                  70                  75                  80  


Leu Leu Ala Ser Lys Cys Val Thr Glu Glu Cys Phe Phe Phe Glu Arg 
                85                  90                  95      


Leu Glu Ser Asn Asn Tyr Asn Thr Tyr Arg Ser Arg Lys Tyr Ser Ser 
            100                 105                 110         


Trp Tyr Val Ala Leu Lys Arg Thr Gly Gln Tyr Lys Leu Gly Ser Lys 
        115                 120                 125             


Thr Gly Pro Gly Gln Lys Ala Ile Leu Phe Leu Pro Met Ser Ala Lys 
    130                 135                 140                 


Ser 
145 


<210>  11
<211>  194
<212>  PRT
<213>  Homo sapiens

<400>  11

Arg Pro Leu Ala Phe Ser Asp Ala Gly Pro His Val His Tyr Gly Trp 
1               5                   10                  15      


Gly Asp Pro Ile Arg Leu Arg His Leu Tyr Thr Ser Gly Pro His Gly 
            20                  25                  30          


Leu Ser Ser Cys Phe Leu Arg Ile Arg Ala Asp Gly Val Val Asp Cys 
        35                  40                  45              


Ala Arg Gly Gln Ser Ala His Ser Leu Leu Glu Ile Lys Ala Val Ala 
    50                  55                  60                  


Leu Arg Thr Val Ala Ile Lys Gly Val His Ser Val Arg Tyr Leu Cys 
65                  70                  75                  80  


Met Gly Ala Asp Gly Lys Met Gln Gly Leu Leu Gln Tyr Ser Glu Glu 
                85                  90                  95      


Asp Cys Ala Phe Glu Glu Glu Ile Arg Pro Asp Gly Tyr Asn Val Tyr 
            100                 105                 110         


Arg Ser Glu Lys His Arg Leu Pro Val Ser Leu Ser Ser Ala Lys Gln 
        115                 120                 125             


Arg Gln Leu Tyr Lys Asn Arg Gly Phe Leu Pro Leu Ser His Phe Leu 
    130                 135                 140                 


Pro Met Leu Pro Met Val Pro Glu Glu Pro Glu Asp Leu Arg Gly His 
145                 150                 155                 160 


Leu Glu Ser Asp Met Phe Ser Ser Pro Leu Glu Thr Asp Ser Met Asp 
                165                 170                 175     


Pro Phe Gly Leu Val Thr Gly Leu Glu Ala Val Arg Ser Pro Ser Phe 
            180                 185                 190         


Glu Lys 
        


