                         SEQUENCE LISTING

<110>  Thoeris GmbH
 
<120>  Use of glutamine synthetase for treating fatty liver disease

<130>  P262989WO

<150>  GB 1815892.3
<151>  2018-09-28

<160>  13    

<170>  PatentIn version 3.5

<210>  1
<211>  373
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Thr Thr Ser Ala Ser Ser His Leu Asn Lys Gly Ile Lys Gln Val 
1               5                   10                  15      


Tyr Met Ser Leu Pro Gln Gly Glu Lys Val Gln Ala Met Tyr Ile Trp 
            20                  25                  30          


Ile Asp Gly Thr Gly Glu Gly Leu Arg Cys Lys Thr Arg Thr Leu Asp 
        35                  40                  45              


Ser Glu Pro Lys Cys Val Glu Glu Leu Pro Glu Trp Asn Phe Asp Gly 
    50                  55                  60                  


Ser Ser Thr Leu Gln Ser Glu Gly Ser Asn Ser Asp Met Tyr Leu Val 
65                  70                  75                  80  


Pro Ala Ala Met Phe Arg Asp Pro Phe Arg Lys Asp Pro Asn Lys Leu 
                85                  90                  95      


Val Leu Cys Glu Val Phe Lys Tyr Asn Arg Arg Pro Ala Glu Thr Asn 
            100                 105                 110         


Leu Arg His Thr Cys Lys Arg Ile Met Asp Met Val Ser Asn Gln His 
        115                 120                 125             


Pro Trp Phe Gly Met Glu Gln Glu Tyr Thr Leu Met Gly Thr Asp Gly 
    130                 135                 140                 


His Pro Phe Gly Trp Pro Ser Asn Gly Phe Pro Gly Pro Gln Gly Pro 
145                 150                 155                 160 


Tyr Tyr Cys Gly Val Gly Ala Asp Arg Ala Tyr Gly Arg Asp Ile Val 
                165                 170                 175     


Glu Ala His Tyr Arg Ala Cys Leu Tyr Ala Gly Val Lys Ile Ala Gly 
            180                 185                 190         


Thr Asn Ala Glu Val Met Pro Ala Gln Trp Glu Phe Gln Ile Gly Pro 
        195                 200                 205             


Cys Glu Gly Ile Ser Met Gly Asp His Leu Trp Val Ala Arg Phe Ile 
    210                 215                 220                 


Leu His Arg Val Cys Glu Asp Phe Gly Val Ile Ala Thr Phe Asp Pro 
225                 230                 235                 240 


Lys Pro Ile Pro Gly Asn Trp Asn Gly Ala Gly Cys His Thr Asn Phe 
                245                 250                 255     


Ser Thr Lys Ala Met Arg Glu Glu Asn Gly Leu Lys Tyr Ile Glu Glu 
            260                 265                 270         


Ala Ile Glu Lys Leu Ser Lys Arg His Gln Tyr His Ile Arg Ala Tyr 
        275                 280                 285             


Asp Pro Lys Gly Gly Leu Asp Asn Ala Arg Arg Leu Thr Gly Phe His 
    290                 295                 300                 


Glu Thr Ser Asn Ile Asn Asp Phe Ser Ala Gly Val Ala Asn Arg Ser 
305                 310                 315                 320 


Ala Ser Ile Arg Ile Pro Arg Thr Val Gly Gln Glu Lys Lys Gly Tyr 
                325                 330                 335     


Phe Glu Asp Arg Arg Pro Ser Ala Asn Cys Asp Pro Phe Ser Val Thr 
            340                 345                 350         


Glu Ala Leu Ile Arg Thr Cys Leu Leu Asn Glu Thr Gly Asp Glu Pro 
        355                 360                 365             


Phe Gln Tyr Lys Asn 
    370             


<210>  2
<211>  372
<212>  PRT
<213>  Homo sapiens

<400>  2

Thr Thr Ser Ala Ser Ser His Leu Asn Lys Gly Ile Lys Gln Val Tyr 
1               5                   10                  15      


Met Ser Leu Pro Gln Gly Glu Lys Val Gln Ala Met Tyr Ile Trp Ile 
            20                  25                  30          


Asp Gly Thr Gly Glu Gly Leu Arg Cys Lys Thr Arg Thr Leu Asp Ser 
        35                  40                  45              


Glu Pro Lys Cys Val Glu Glu Leu Pro Glu Trp Asn Phe Asp Gly Ser 
    50                  55                  60                  


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


Ala Ala Met Phe Arg Asp Pro Phe Arg Lys Asp Pro Asn Lys Leu Val 
                85                  90                  95      


Leu Cys Glu Val Phe Lys Tyr Asn Arg Arg Pro Ala Glu Thr Asn Leu 
            100                 105                 110         


Arg His Thr Cys Lys Arg Ile Met Asp Met Val Ser Asn Gln His Pro 
        115                 120                 125             


Trp Phe Gly Met Glu Gln Glu Tyr Thr Leu Met Gly Thr Asp Gly His 
    130                 135                 140                 


Pro Phe Gly Trp Pro Ser Asn Gly Phe Pro Gly Pro Gln Gly Pro Tyr 
145                 150                 155                 160 


Tyr Cys Gly Val Gly Ala Asp Arg Ala Tyr Gly Arg Asp Ile Val Glu 
                165                 170                 175     


Ala His Tyr Arg Ala Cys Leu Tyr Ala Gly Val Lys Ile Ala Gly Thr 
            180                 185                 190         


Asn Ala Glu Val Met Pro Ala Gln Trp Glu Phe Gln Ile Gly Pro Cys 
        195                 200                 205             


Glu Gly Ile Ser Met Gly Asp His Leu Trp Val Ala Arg Phe Ile Leu 
    210                 215                 220                 


His Arg Val Cys Glu Asp Phe Gly Val Ile Ala Thr Phe Asp Pro Lys 
225                 230                 235                 240 


Pro Ile Pro Gly Asn Trp Asn Gly Ala Gly Cys His Thr Asn Phe Ser 
                245                 250                 255     


Thr Lys Ala Met Arg Glu Glu Asn Gly Leu Lys Tyr Ile Glu Glu Ala 
            260                 265                 270         


Ile Glu Lys Leu Ser Lys Arg His Gln Tyr His Ile Arg Ala Tyr Asp 
        275                 280                 285             


Pro Lys Gly Gly Leu Asp Asn Ala Arg Arg Leu Thr Gly Phe His Glu 
    290                 295                 300                 


Thr Ser Asn Ile Asn Asp Phe Ser Ala Gly Val Ala Asn Arg Ser Ala 
305                 310                 315                 320 


Ser Ile Arg Ile Pro Arg Thr Val Gly Gln Glu Lys Lys Gly Tyr Phe 
                325                 330                 335     


Glu Asp Arg Arg Pro Ser Ala Asn Cys Asp Pro Phe Ser Val Thr Glu 
            340                 345                 350         


Ala Leu Ile Arg Thr Cys Leu Leu Asn Glu Thr Gly Asp Glu Pro Phe 
        355                 360                 365             


Gln Tyr Lys Asn 
    370         


<210>  3
<211>  1366
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  cDNA sequence of SEQ ID NO 1

<400>  3
cgagagtggg agaagagcgg agcgtgtgag cagtactgcg gcctcctctc ctctcctaac       60

ctgctctcgc ggcctacctt tacccgcccg cctgctcggc gaccagaaca ccttccacca      120

tgaccacctc agcaagttcc cacttaaata aaggcatcaa gcaggtgtac atgtccctgc      180

ctcagggtga gaaagtccag gccatgtata tctggatcga tggtactgga gaaggactgc      240

gctgcaagac ccggaccctg gacagtgagc ccaagtgtgt ggaagagttg cctgagtgga      300

atttcgatgg ctccagtact ttacagtctg agggttccaa cagtgacatg tatctcgtgc      360

ctgctgccat gtttcgggac cccttccgta aggaccctaa caagctggtg ttatgtgaag      420

ttttcaagta caatcgaagg cctgcagaga ccaatttgag gcacacctgt aaacggataa      480

tggacatggt gagcaaccag cacccctggt ttggcatgga gcaggagtat accctcatgg      540

ggacagatgg gcaccccttt ggttggcctt ccaacggctt cccagggccc cagggtccat      600

attactgtgg tgtgggagca gacagagcct atggcaggga catcgtggag gcccattacc      660

gggcctgctt gtatgctgga gtcaagattg cggggactaa tgccgaggtc atgcctgccc      720

agtgggaatt tcagattgga ccttgtgaag gaatcagcat gggagatcat ctctgggtgg      780

cccgtttcat cttgcatcgt gtgtgtgaag actttggagt gatagcaacc tttgatccta      840

agcccattcc tgggaactgg aatggtgcag gctgccatac caacttcagc accaaggcca      900

tgcgggagga gaatggtctg aagtacatcg aggaggccat tgagaaacta agcaagcggc      960

accagtacca catccgtgcc tatgatccca agggaggcct ggacaatgcc cgacgtctaa     1020

ctggattcca tgaaacctcc aacatcaacg acttttctgg tggtgtagcc aatcgtagcg     1080

ccagcatacg cattccccgg actgttggcc aggagaagaa gggttacttt gaagatcgtc     1140

gcccctctgc caactgcgac cccttttcgg tgacagaagc cctcatccgc acgtgtcttc     1200

tcaatgaaac cggcgatgag cccttccagt acaaaaatta agtggactag acctccagct     1260

gttgagcccc tcctagttct tcatcccact ccaactcttc cccctctccc agttgtcccg     1320

attgtaactc aaagggtgga atatcaaggt cgtttttttt cattcc                    1366


<210>  4
<211>  388
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GS protein grown in bacteria, used in Example 1

<400>  4

Met Gly Ser Ser His His His His His His Gly Gly Gly Gly Ser Met 
1               5                   10                  15      


Thr Thr Ser Ala Ser Ser His Leu Asn Lys Gly Ile Lys Gln Val Tyr 
            20                  25                  30          


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


Asp Gly Thr Gly Glu Gly Leu Arg Cys Lys Thr Arg Thr Leu Asp Ser 
    50                  55                  60                  


Glu Pro Lys Cys Val Glu Glu Leu Pro Glu Trp Asn Phe Asp Gly Ser 
65                  70                  75                  80  


Ser Thr Leu Gln Ser Glu Gly Ser Asn Ser Asp Met Tyr Leu Val Pro 
                85                  90                  95      


Ala Ala Met Phe Arg Asp Pro Phe Arg Lys Asp Pro Asn Lys Leu Val 
            100                 105                 110         


Leu Cys Glu Val Phe Lys Tyr Asn Arg Arg Pro Ala Glu Thr Asn Leu 
        115                 120                 125             


Arg His Thr Cys Lys Arg Ile Met Asp Met Val Ser Asn Gln His Pro 
    130                 135                 140                 


Trp Phe Gly Met Glu Gln Glu Tyr Thr Leu Met Gly Thr Asp Gly His 
145                 150                 155                 160 


Pro Phe Gly Trp Pro Ser Asn Gly Phe Pro Gly Pro Gln Gly Pro Tyr 
                165                 170                 175     


Tyr Cys Gly Val Gly Ala Asp Arg Ala Tyr Gly Arg Asp Ile Val Glu 
            180                 185                 190         


Ala His Tyr Arg Ala Cys Leu Tyr Ala Gly Val Lys Ile Ala Gly Thr 
        195                 200                 205             


Asn Ala Glu Val Met Pro Ala Gln Trp Glu Phe Gln Ile Gly Pro Cys 
    210                 215                 220                 


Glu Gly Ile Ser Met Gly Asp His Leu Trp Val Ala Arg Phe Ile Leu 
225                 230                 235                 240 


His Arg Val Cys Glu Asp Phe Gly Val Ile Ala Thr Phe Asp Pro Lys 
                245                 250                 255     


Pro Ile Pro Gly Asn Trp Asn Gly Ala Gly Cys His Thr Asn Phe Ser 
            260                 265                 270         


Thr Lys Ala Met Arg Glu Glu Asn Gly Leu Lys Tyr Ile Glu Glu Ala 
        275                 280                 285             


Ile Glu Lys Leu Ser Lys Arg His Gln Tyr His Ile Arg Ala Tyr Asp 
    290                 295                 300                 


Pro Lys Gly Gly Leu Asp Asn Ala Arg Arg Leu Thr Gly Phe His Glu 
305                 310                 315                 320 


Thr Ser Asn Ile Asn Asp Phe Ser Ala Gly Val Ala Asn Arg Ser Ala 
                325                 330                 335     


Ser Ile Arg Ile Pro Arg Thr Val Gly Gln Glu Lys Lys Gly Tyr Phe 
            340                 345                 350         


Glu Asp Arg Arg Pro Ser Ala Asn Cys Asp Pro Phe Ser Val Thr Glu 
        355                 360                 365             


Ala Leu Ile Arg Thr Cys Leu Leu Asn Glu Thr Gly Asp Glu Pro Phe 
    370                 375                 380                 


Gln Tyr Lys Asn 
385             


<210>  5
<211>  1164
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  bacterial optimised cDNA of the protein used in Example 1

<400>  5
atgggcagca gccaccacca tcaccaccac ggcggcggcg gtagcatgac cacctcggca       60

agcagccacc tgaataaagg catcaaacag gtgtatatgt ctctgccgca gggtgaaaaa      120

gttcaagcca tgtacatttg gatcgatggc accggtgaag gcctgcgttg caaaacccgc      180

acgctggact cagaaccgaa atgtgtggaa gaactgccgg aatggaactt tgatggtagc      240

tctacgctgc agtcggaagg cagtaattcc gacatgtatc tggttccggc ggccatgttt      300

cgtgatccgt tccgcaaaga cccgaacaaa ctggtgctgt gcgaagtttt taaatacaac      360

cgtcgcccgg cggaaaccaa tctgcgtcat acgtgtaaac gcattatgga tatggtcagc      420

aaccagcacc cgtggttcgg tatggaacaa gaatataccc tgatgggtac ggatggccat      480

ccgtttggtt ggccgagcaa tggtttcccg ggtccgcagg gtccgtatta ctgcggtgtc      540

ggcgcagatc gtgcttacgg tcgcgacatt gtggaagcac actatcgtgc ttgtctgtac      600

gcgggtgtta aaatcgccgg caccaatgca gaagtcatgc cggctcagtg ggaatttcaa      660

attggcccgt gcgaaggtat cagcatgggc gatcatctgt gggttgctcg tttcatcctg      720

caccgcgtct gtgaagattt tggtgtgatt gcgaccttcg acccgaaacc gatcccgggc      780

aactggaatg gtgctggctg ccataccaac tttagcacga aagcgatgcg tgaagaaaat      840

ggcctgaaat acatcgaaga agcaatcgaa aaactgtcta aacgtcatca gtatcacatt      900

cgcgcctacg atccgaaagg cggtctggac aacgcacgtc gcctgaccgg ttttcacgaa      960

acgagcaaca tcaatgattt ctctgcgggc gttgccaatc gctcagcctc gattcgtatc     1020

ccgcgcaccg tcggtcaaga gaaaaaaggc tattttgaag atcgtcgccc gagtgcaaac     1080

tgtgacccgt tctccgtgac ggaagccctg atccgcacct gtctgctgaa tgaaaccggc     1140

gatgaaccgt tccaatacaa aaat                                            1164


<210>  6
<211>  445
<212>  PRT
<213>  Lactobacillus acidophilus

<400>  6

Met Ser Lys Gln Tyr Thr Thr Glu Glu Ile Arg Lys Glu Val Ala Asp 
1               5                   10                  15      


Lys Asp Val Arg Phe Leu Arg Leu Cys Phe Thr Asp Ile Asn Gly Thr 
            20                  25                  30          


Glu Lys Ala Val Glu Val Pro Thr Ser Gln Leu Asp Lys Val Leu Thr 
        35                  40                  45              


Asn Asp Ile Arg Phe Asp Gly Ser Ser Ile Asp Gly Phe Val Arg Leu 
    50                  55                  60                  


Glu Glu Ser Asp Met Val Leu Tyr Pro Asp Phe Ser Thr Trp Ser Val 
65                  70                  75                  80  


Leu Pro Trp Gly Asp Glu His Gly Gly Lys Ile Gly Arg Leu Ile Cys 
                85                  90                  95      


Ser Val His Met Thr Asp Gly Lys Pro Phe Ala Gly Asp Pro Arg Asn 
            100                 105                 110         


Asn Leu Lys Arg Val Leu Gly Glu Met Lys Glu Ala Gly Phe Asp Thr 
        115                 120                 125             


Phe Asp Ile Gly Phe Glu Met Glu Phe His Leu Phe Lys Leu Asp Glu 
    130                 135                 140                 


Asn Gly Asn Trp Thr Thr Glu Val Pro Asp His Ala Ser Tyr Phe Asp 
145                 150                 155                 160 


Met Thr Ser Asp Asp Glu Gly Ala Arg Cys Arg Arg Glu Ile Val Glu 
                165                 170                 175     


Thr Leu Glu Glu Ile Gly Phe Glu Val Glu Ala Ala His His Glu Val 
            180                 185                 190         


Gly Asp Gly Gln Gln Glu Ile Asp Phe Arg Phe Asp Asp Ala Leu Thr 
        195                 200                 205             


Thr Ala Asp Arg Cys Gln Thr Phe Lys Met Val Ala Arg His Ile Ala 
    210                 215                 220                 


Arg Lys His Gly Leu Phe Ala Thr Phe Met Ala Lys Pro Val Glu Gly 
225                 230                 235                 240 


Gln Ala Gly Asn Gly Met His Asn Asn Met Ser Leu Phe Lys Asn Lys 
                245                 250                 255     


His Asn Val Phe Tyr Asp Lys Asp Gly Glu Phe His Leu Ser Asn Thr 
            260                 265                 270         


Ala Leu Tyr Phe Leu Asn Gly Ile Leu Glu His Ala Arg Ala Ile Thr 
        275                 280                 285             


Ala Ile Gly Asn Pro Thr Val Asn Ser Tyr Lys Arg Leu Ile Pro Gly 
    290                 295                 300                 


Phe Glu Ala Pro Val Tyr Ile Ala Trp Ala Ala Lys Asn Arg Ser Pro 
305                 310                 315                 320 


Leu Val Arg Ile Pro Ser Ala Gly Glu Ile Asn Thr Arg Leu Glu Met 
                325                 330                 335     


Arg Ser Ala Asp Pro Thr Ala Asn Pro Tyr Leu Leu Leu Ala Ala Cys 
            340                 345                 350         


Leu Thr Ala Gly Leu Lys Gly Ile Lys Glu Gln Lys Met Pro Met Lys 
        355                 360                 365             


Pro Val Glu Glu Asn Ile Phe Glu Met Thr Glu Glu Glu Arg Ala Glu 
    370                 375                 380                 


His Gly Ile Lys Pro Leu Pro Thr Thr Leu His Asn Ala Ile Lys Ala 
385                 390                 395                 400 


Phe Lys Glu Asp Asp Leu Ile Lys Ser Ala Leu Gly Glu His Leu Thr 
                405                 410                 415     


His Ser Phe Ile Glu Ser Lys Glu Leu Glu Trp Ser Lys Tyr Ser Gln 
            420                 425                 430         


Ser Val Ser Asp Trp Glu Arg Gln Arg Tyr Met Asn Trp 
        435                 440                 445 


<210>  7
<211>  356
<212>  PRT
<213>  Zea mays

<400>  7

Met Ala Cys Leu Thr Asp Leu Val Asn Leu Asn Leu Ser Asp Asn Thr 
1               5                   10                  15      


Glu Lys Ile Ile Ala Glu Tyr Ile Trp Ile Gly Gly Ser Gly Met Asp 
            20                  25                  30          


Leu Arg Ser Lys Ala Arg Thr Leu Ser Gly Pro Val Thr Asp Pro Ser 
        35                  40                  45              


Lys Leu Pro Lys Trp Asn Tyr Asp Gly Ser Ser Thr Gly Gln Ala Pro 
    50                  55                  60                  


Gly Glu Asp Ser Glu Val Ile Leu Tyr Pro Gln Ala Ile Phe Lys Asp 
65                  70                  75                  80  


Pro Phe Arg Arg Gly Asn Asn Ile Leu Val Met Cys Asp Cys Tyr Thr 
                85                  90                  95      


Pro Ala Gly Glu Pro Ile Pro Thr Asn Lys Arg Tyr Asn Ala Ala Lys 
            100                 105                 110         


Ile Phe Ser Ser Pro Glu Val Ala Ala Glu Glu Pro Trp Tyr Gly Ile 
        115                 120                 125             


Glu Gln Glu Tyr Thr Leu Leu Gln Lys Asp Thr Asn Trp Pro Leu Gly 
    130                 135                 140                 


Trp Pro Ile Gly Gly Phe Pro Gly Pro Gln Gly Pro Tyr Tyr Cys Gly 
145                 150                 155                 160 


Ile Gly Ala Glu Lys Ser Phe Gly Arg Asp Ile Val Asp Ala His Tyr 
                165                 170                 175     


Lys Ala Cys Leu Tyr Ala Gly Ile Asn Ile Ser Gly Ile Asn Gly Glu 
            180                 185                 190         


Val Met Pro Gly Gln Trp Glu Phe Gln Val Gly Pro Ser Val Gly Ile 
        195                 200                 205             


Ser Ser Gly Asp Gln Val Trp Val Ala Arg Tyr Ile Leu Glu Arg Ile 
    210                 215                 220                 


Thr Glu Ile Ala Gly Val Val Val Thr Phe Asp Pro Lys Pro Ile Pro 
225                 230                 235                 240 


Gly Asp Trp Asn Gly Ala Gly Ala His Thr Asn Tyr Ser Thr Glu Ser 
                245                 250                 255     


Met Arg Lys Glu Gly Gly Tyr Glu Val Ile Lys Ala Ala Ile Glu Lys 
            260                 265                 270         


Leu Lys Leu Arg His Arg Glu His Ile Ala Ala Tyr Gly Glu Gly Asn 
        275                 280                 285             


Glu Arg Arg Leu Thr Gly Arg His Glu Thr Ala Asp Ile Asn Thr Phe 
    290                 295                 300                 


Ser Trp Gly Val Ala Asn Arg Gly Ala Ser Val Arg Val Gly Arg Glu 
305                 310                 315                 320 


Thr Glu Gln Asn Gly Lys Gly Tyr Phe Glu Asp Arg Arg Pro Ala Ser 
                325                 330                 335     


Asn Met Asp Pro Tyr Val Val Thr Ser Met Ile Ala Glu Thr Thr Ile 
            340                 345                 350         


Ile Trp Lys Pro 
        355     


<210>  8
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  8

Gly Gly Gly Ser 
1               


<210>  9
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  9

Gly Gly Gly Gly Ser 
1               5   


<210>  10
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  poly(his) tag

<400>  10

His His His His His His 
1               5       


<210>  11
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GS sequence

<400>  11

Gly Gly Gly Ser His His His His His His Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


Ser 
    


<210>  12
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  N terminal of human recombinant GS

<400>  12

Gly Gly Gly Ser His His His His His His Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  13
<211>  4
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  13

Gly Gly Ser Gly 
1               


