                         LISTADO DE SECUENCIAS

<110>  Fundacin Pblica Andaluza Progreso y Salud
 
<120>  ENZIMAS GLUCOCINASAS CON ACTIVIDAD AUMENTADA Y SU USO EN EL 
       TRATAMIENTO Y/O PREVENCIN DE LA DIABETES MELLITUS

<130>  PCT1985.91

<160>  16    

<170>  PatentIn version 3.5

<210>  1
<211>  465
<212>  PRT
<213>  Secuencia Artificial

<220>
<223>  Variante de la invencin GCK-S64F

<400>  1

Met Leu Asp Asp Arg Ala Arg Met Glu Ala Ala Lys Lys Glu Lys Val 
1               5                   10                  15      


Glu Gln Ile Leu Ala Glu Phe Gln Leu Gln Glu Glu Asp Leu Lys Lys 
            20                  25                  30          


Val Met Arg Arg Met Gln Lys Glu Met Asp Arg Gly Leu Arg Leu Glu 
        35                  40                  45              


Thr His Glu Glu Ala Ser Val Lys Met Leu Pro Thr Tyr Val Arg Phe 
    50                  55                  60                  


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


Gly Thr Asn Phe Arg Val Met Leu Val Lys Val Gly Glu Gly Glu Glu 
                85                  90                  95      


Gly Gln Trp Ser Val Lys Thr Lys His Gln Met Tyr Ser Ile Pro Glu 
            100                 105                 110         


Asp Ala Met Thr Gly Thr Ala Glu Met Leu Phe Asp Tyr Ile Ser Glu 
        115                 120                 125             


Cys Ile Ser Asp Phe Leu Asp Lys His Gln Met Lys His Lys Lys Leu 
    130                 135                 140                 


Pro Leu Gly Phe Thr Phe Ser Phe Pro Val Arg His Glu Asp Ile Asp 
145                 150                 155                 160 


Lys Gly Ile Leu Leu Asn Trp Thr Lys Gly Phe Lys Ala Ser Gly Ala 
                165                 170                 175     


Glu Gly Asn Asn Val Val Gly Leu Leu Arg Asp Ala Ile Lys Arg Arg 
            180                 185                 190         


Gly Asp Phe Glu Met Asp Val Val Ala Met Val Asn Asp Thr Val Ala 
        195                 200                 205             


Thr Met Ile Ser Cys Tyr Tyr Glu Asp His Gln Cys Glu Val Gly Met 
    210                 215                 220                 


Ile Val Gly Thr Gly Cys Asn Ala Cys Tyr Met Glu Glu Met Gln Asn 
225                 230                 235                 240 


Val Glu Leu Val Glu Gly Asp Glu Gly Arg Met Cys Val Asn Thr Glu 
                245                 250                 255     


Trp Gly Ala Phe Gly Asp Ser Gly Glu Leu Asp Glu Phe Leu Leu Glu 
            260                 265                 270         


Tyr Asp Arg Leu Val Asp Glu Ser Ser Ala Asn Pro Gly Gln Gln Leu 
        275                 280                 285             


Tyr Glu Lys Leu Ile Gly Gly Lys Tyr Met Gly Glu Leu Val Arg Leu 
    290                 295                 300                 


Val Leu Leu Arg Leu Val Asp Glu Asn Leu Leu Phe His Gly Glu Ala 
305                 310                 315                 320 


Ser Glu Gln Leu Arg Thr Arg Gly Ala Phe Glu Thr Arg Phe Val Ser 
                325                 330                 335     


Gln Val Glu Ser Asp Thr Gly Asp Arg Lys Gln Ile Tyr Asn Ile Leu 
            340                 345                 350         


Ser Thr Leu Gly Leu Arg Pro Ser Thr Thr Asp Cys Asp Ile Val Arg 
        355                 360                 365             


Arg Ala Cys Glu Ser Val Ser Thr Arg Ala Ala His Met Cys Ser Ala 
    370                 375                 380                 


Gly Leu Ala Gly Val Ile Asn Arg Met Arg Glu Ser Arg Ser Glu Asp 
385                 390                 395                 400 


Val Met Arg Ile Thr Val Gly Val Asp Gly Ser Val Tyr Lys Leu His 
                405                 410                 415     


Pro Ser Phe Lys Glu Arg Phe His Ala Ser Val Arg Arg Leu Thr Pro 
            420                 425                 430         


Ser Cys Glu Ile Thr Phe Ile Glu Ser Glu Glu Gly Ser Gly Arg Gly 
        435                 440                 445             


Ala Ala Leu Val Ser Ala Val Ala Cys Lys Lys Ala Cys Met Leu Gly 
    450                 455                 460                 


Gln 
465 


<210>  2
<211>  465
<212>  PRT
<213>  Secuencia Artificial

<220>
<223>  Variante de la invencin GCK-V91L

<400>  2

Met Leu Asp Asp Arg Ala Arg Met Glu Ala Ala Lys Lys Glu Lys Val 
1               5                   10                  15      


Glu Gln Ile Leu Ala Glu Phe Gln Leu Gln Glu Glu Asp Leu Lys Lys 
            20                  25                  30          


Val Met Arg Arg Met Gln Lys Glu Met Asp Arg Gly Leu Arg Leu Glu 
        35                  40                  45              


Thr His Glu Glu Ala Ser Val Lys Met Leu Pro Thr Tyr Val Arg Ser 
    50                  55                  60                  


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


Gly Thr Asn Phe Arg Val Met Leu Val Lys Leu Gly Glu Gly Glu Glu 
                85                  90                  95      


Gly Gln Trp Ser Val Lys Thr Lys His Gln Met Tyr Ser Ile Pro Glu 
            100                 105                 110         


Asp Ala Met Thr Gly Thr Ala Glu Met Leu Phe Asp Tyr Ile Ser Glu 
        115                 120                 125             


Cys Ile Ser Asp Phe Leu Asp Lys His Gln Met Lys His Lys Lys Leu 
    130                 135                 140                 


Pro Leu Gly Phe Thr Phe Ser Phe Pro Val Arg His Glu Asp Ile Asp 
145                 150                 155                 160 


Lys Gly Ile Leu Leu Asn Trp Thr Lys Gly Phe Lys Ala Ser Gly Ala 
                165                 170                 175     


Glu Gly Asn Asn Val Val Gly Leu Leu Arg Asp Ala Ile Lys Arg Arg 
            180                 185                 190         


Gly Asp Phe Glu Met Asp Val Val Ala Met Val Asn Asp Thr Val Ala 
        195                 200                 205             


Thr Met Ile Ser Cys Tyr Tyr Glu Asp His Gln Cys Glu Val Gly Met 
    210                 215                 220                 


Ile Val Gly Thr Gly Cys Asn Ala Cys Tyr Met Glu Glu Met Gln Asn 
225                 230                 235                 240 


Val Glu Leu Val Glu Gly Asp Glu Gly Arg Met Cys Val Asn Thr Glu 
                245                 250                 255     


Trp Gly Ala Phe Gly Asp Ser Gly Glu Leu Asp Glu Phe Leu Leu Glu 
            260                 265                 270         


Tyr Asp Arg Leu Val Asp Glu Ser Ser Ala Asn Pro Gly Gln Gln Leu 
        275                 280                 285             


Tyr Glu Lys Leu Ile Gly Gly Lys Tyr Met Gly Glu Leu Val Arg Leu 
    290                 295                 300                 


Val Leu Leu Arg Leu Val Asp Glu Asn Leu Leu Phe His Gly Glu Ala 
305                 310                 315                 320 


Ser Glu Gln Leu Arg Thr Arg Gly Ala Phe Glu Thr Arg Phe Val Ser 
                325                 330                 335     


Gln Val Glu Ser Asp Thr Gly Asp Arg Lys Gln Ile Tyr Asn Ile Leu 
            340                 345                 350         


Ser Thr Leu Gly Leu Arg Pro Ser Thr Thr Asp Cys Asp Ile Val Arg 
        355                 360                 365             


Arg Ala Cys Glu Ser Val Ser Thr Arg Ala Ala His Met Cys Ser Ala 
    370                 375                 380                 


Gly Leu Ala Gly Val Ile Asn Arg Met Arg Glu Ser Arg Ser Glu Asp 
385                 390                 395                 400 


Val Met Arg Ile Thr Val Gly Val Asp Gly Ser Val Tyr Lys Leu His 
                405                 410                 415     


Pro Ser Phe Lys Glu Arg Phe His Ala Ser Val Arg Arg Leu Thr Pro 
            420                 425                 430         


Ser Cys Glu Ile Thr Phe Ile Glu Ser Glu Glu Gly Ser Gly Arg Gly 
        435                 440                 445             


Ala Ala Leu Val Ser Ala Val Ala Cys Lys Lys Ala Cys Met Leu Gly 
    450                 455                 460                 


Gln 
465 


<210>  3
<211>  465
<212>  PRT
<213>  Secuencia Artificial

<220>
<223>  Variante de la invencin GCK-Y214C

<400>  3

Met Leu Asp Asp Arg Ala Arg Met Glu Ala Ala Lys Lys Glu Lys Val 
1               5                   10                  15      


Glu Gln Ile Leu Ala Glu Phe Gln Leu Gln Glu Glu Asp Leu Lys Lys 
            20                  25                  30          


Val Met Arg Arg Met Gln Lys Glu Met Asp Arg Gly Leu Arg Leu Glu 
        35                  40                  45              


Thr His Glu Glu Ala Ser Val Lys Met Leu Pro Thr Tyr Val Arg Ser 
    50                  55                  60                  


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


Gly Thr Asn Phe Arg Val Met Leu Val Lys Val Gly Glu Gly Glu Glu 
                85                  90                  95      


Gly Gln Trp Ser Val Lys Thr Lys His Gln Met Tyr Ser Ile Pro Glu 
            100                 105                 110         


Asp Ala Met Thr Gly Thr Ala Glu Met Leu Phe Asp Tyr Ile Ser Glu 
        115                 120                 125             


Cys Ile Ser Asp Phe Leu Asp Lys His Gln Met Lys His Lys Lys Leu 
    130                 135                 140                 


Pro Leu Gly Phe Thr Phe Ser Phe Pro Val Arg His Glu Asp Ile Asp 
145                 150                 155                 160 


Lys Gly Ile Leu Leu Asn Trp Thr Lys Gly Phe Lys Ala Ser Gly Ala 
                165                 170                 175     


Glu Gly Asn Asn Val Val Gly Leu Leu Arg Asp Ala Ile Lys Arg Arg 
            180                 185                 190         


Gly Asp Phe Glu Met Asp Val Val Ala Met Val Asn Asp Thr Val Ala 
        195                 200                 205             


Thr Met Ile Ser Cys Cys Tyr Glu Asp His Gln Cys Glu Val Gly Met 
    210                 215                 220                 


Ile Val Gly Thr Gly Cys Asn Ala Cys Tyr Met Glu Glu Met Gln Asn 
225                 230                 235                 240 


Val Glu Leu Val Glu Gly Asp Glu Gly Arg Met Cys Val Asn Thr Glu 
                245                 250                 255     


Trp Gly Ala Phe Gly Asp Ser Gly Glu Leu Asp Glu Phe Leu Leu Glu 
            260                 265                 270         


Tyr Asp Arg Leu Val Asp Glu Ser Ser Ala Asn Pro Gly Gln Gln Leu 
        275                 280                 285             


Tyr Glu Lys Leu Ile Gly Gly Lys Tyr Met Gly Glu Leu Val Arg Leu 
    290                 295                 300                 


Val Leu Leu Arg Leu Val Asp Glu Asn Leu Leu Phe His Gly Glu Ala 
305                 310                 315                 320 


Ser Glu Gln Leu Arg Thr Arg Gly Ala Phe Glu Thr Arg Phe Val Ser 
                325                 330                 335     


Gln Val Glu Ser Asp Thr Gly Asp Arg Lys Gln Ile Tyr Asn Ile Leu 
            340                 345                 350         


Ser Thr Leu Gly Leu Arg Pro Ser Thr Thr Asp Cys Asp Ile Val Arg 
        355                 360                 365             


Arg Ala Cys Glu Ser Val Ser Thr Arg Ala Ala His Met Cys Ser Ala 
    370                 375                 380                 


Gly Leu Ala Gly Val Ile Asn Arg Met Arg Glu Ser Arg Ser Glu Asp 
385                 390                 395                 400 


Val Met Arg Ile Thr Val Gly Val Asp Gly Ser Val Tyr Lys Leu His 
                405                 410                 415     


Pro Ser Phe Lys Glu Arg Phe His Ala Ser Val Arg Arg Leu Thr Pro 
            420                 425                 430         


Ser Cys Glu Ile Thr Phe Ile Glu Ser Glu Glu Gly Ser Gly Arg Gly 
        435                 440                 445             


Ala Ala Leu Val Ser Ala Val Ala Cys Lys Lys Ala Cys Met Leu Gly 
    450                 455                 460                 


Gln 
465 


<210>  4
<211>  465
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Leu Asp Asp Arg Ala Arg Met Glu Ala Ala Lys Lys Glu Lys Val 
1               5                   10                  15      


Glu Gln Ile Leu Ala Glu Phe Gln Leu Gln Glu Glu Asp Leu Lys Lys 
            20                  25                  30          


Val Met Arg Arg Met Gln Lys Glu Met Asp Arg Gly Leu Arg Leu Glu 
        35                  40                  45              


Thr His Glu Glu Ala Ser Val Lys Met Leu Pro Thr Tyr Val Arg Ser 
    50                  55                  60                  


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


Gly Thr Asn Phe Arg Val Met Leu Val Lys Val Gly Glu Gly Glu Glu 
                85                  90                  95      


Gly Gln Trp Ser Val Lys Thr Lys His Gln Met Tyr Ser Ile Pro Glu 
            100                 105                 110         


Asp Ala Met Thr Gly Thr Ala Glu Met Leu Phe Asp Tyr Ile Ser Glu 
        115                 120                 125             


Cys Ile Ser Asp Phe Leu Asp Lys His Gln Met Lys His Lys Lys Leu 
    130                 135                 140                 


Pro Leu Gly Phe Thr Phe Ser Phe Pro Val Arg His Glu Asp Ile Asp 
145                 150                 155                 160 


Lys Gly Ile Leu Leu Asn Trp Thr Lys Gly Phe Lys Ala Ser Gly Ala 
                165                 170                 175     


Glu Gly Asn Asn Val Val Gly Leu Leu Arg Asp Ala Ile Lys Arg Arg 
            180                 185                 190         


Gly Asp Phe Glu Met Asp Val Val Ala Met Val Asn Asp Thr Val Ala 
        195                 200                 205             


Thr Met Ile Ser Cys Tyr Tyr Glu Asp His Gln Cys Glu Val Gly Met 
    210                 215                 220                 


Ile Val Gly Thr Gly Cys Asn Ala Cys Tyr Met Glu Glu Met Gln Asn 
225                 230                 235                 240 


Val Glu Leu Val Glu Gly Asp Glu Gly Arg Met Cys Val Asn Thr Glu 
                245                 250                 255     


Trp Gly Ala Phe Gly Asp Ser Gly Glu Leu Asp Glu Phe Leu Leu Glu 
            260                 265                 270         


Tyr Asp Arg Leu Val Asp Glu Ser Ser Ala Asn Pro Gly Gln Gln Leu 
        275                 280                 285             


Tyr Glu Lys Leu Ile Gly Gly Lys Tyr Met Gly Glu Leu Val Arg Leu 
    290                 295                 300                 


Val Leu Leu Arg Leu Val Asp Glu Asn Leu Leu Phe His Gly Glu Ala 
305                 310                 315                 320 


Ser Glu Gln Leu Arg Thr Arg Gly Ala Phe Glu Thr Arg Phe Val Ser 
                325                 330                 335     


Gln Val Glu Ser Asp Thr Gly Asp Arg Lys Gln Ile Tyr Asn Ile Leu 
            340                 345                 350         


Ser Thr Leu Gly Leu Arg Pro Ser Thr Thr Asp Cys Asp Ile Val Arg 
        355                 360                 365             


Arg Ala Cys Glu Ser Val Ser Thr Arg Ala Ala His Met Cys Ser Ala 
    370                 375                 380                 


Gly Leu Ala Gly Val Ile Asn Arg Met Arg Glu Ser Arg Ser Glu Asp 
385                 390                 395                 400 


Val Met Arg Ile Thr Val Gly Val Asp Gly Ser Val Tyr Lys Leu His 
                405                 410                 415     


Pro Ser Phe Lys Glu Arg Phe His Ala Ser Val Arg Arg Leu Thr Pro 
            420                 425                 430         


Ser Cys Glu Ile Thr Phe Ile Glu Ser Glu Glu Gly Ser Gly Arg Gly 
        435                 440                 445             


Ala Ala Leu Val Ser Ala Val Ala Cys Lys Lys Ala Cys Met Leu Gly 
    450                 455                 460                 


Gln 
465 


<210>  5
<211>  2731
<212>  DNA
<213>  Homo sapiens

<400>  5
ccgagcggcg cctgagcccc agggaagcag gctaggatgt gagagacaca gtcacctgca       60

gcctaattac tcaaaagctg tccccaggtc acagaaggga gaggacattt cccactgaat      120

ctgtctgaag gacactaagc cccacagctc aacacaacca ggagagaaag cgctgaggac      180

gccacccaag cgcccagcaa tggccctgcc tggagaacat ccaggctcag tgaggaaggg      240

tccagaaggg aatgcttgcc gactcgttgg agaacaatga aaaggaggaa actgtgactg      300

aacctcaaac cccaaaccag cccgaggaga accacattct cccagggacc cagggcgggc      360

cgtgacccct gcggcggaga agccttggat atttccactt cagaagccta ctggggaagg      420

ctgaggggtc ccagctcccc acgctggctg ctgtgcagat gctggacgac agagccagga      480

tggaggccgc caagaaggag aaggtagagc agatcctggc agagttccag ctgcaggagg      540

aggacctgaa gaaggtgatg agacggatgc agaaggagat ggaccgcggc ctgaggctgg      600

agacccatga agaggccagt gtgaagatgc tgcccaccta cgtgcgctcc accccagaag      660

gctcagaagt cggggacttc ctctccctgg acctgggtgg cactaacttc agggtgatgc      720

tggtgaaggt gggagaaggt gaggaggggc agtggagcgt gaagaccaaa caccagatgt      780

actccatccc cgaggacgcc atgaccggca ctgctgagat gctcttcgac tacatctctg      840

agtgcatctc cgacttcctg gacaagcatc agatgaaaca caagaagctg cccctgggct      900

tcaccttctc ctttcctgtg aggcacgaag acatcgataa gggcatcctt ctcaactgga      960

ccaagggctt caaggcctca ggagcagaag ggaacaatgt cgtggggctt ctgcgagacg     1020

ctatcaaacg gagaggggac tttgaaatgg atgtggtggc aatggtgaat gacacggtgg     1080

ccacgatgat ctcctgctac tacgaagacc atcagtgcga ggtcggcatg atcgtgggca     1140

cgggctgcaa tgcctgctac atggaggaga tgcagaatgt ggagctggtg gagggggacg     1200

agggccgcat gtgcgtcaat accgagtggg gcgccttcgg ggactccggc gagctggacg     1260

agttcctgct ggagtatgac cgcctggtgg acgagagctc tgcaaacccc ggtcagcagc     1320

tgtatgagaa gctcataggt ggcaagtaca tgggcgagct ggtgcggctt gtgctgctca     1380

ggctcgtgga cgaaaacctg ctcttccacg gggaggcctc cgagcagctg cgcacacgcg     1440

gagccttcga gacgcgcttc gtgtcgcagg tggagagcga cacgggcgac cgcaagcaga     1500

tctacaacat cctgagcacg ctggggctgc gaccctcgac caccgactgc gacatcgtgc     1560

gccgcgcctg cgagagcgtg tctacgcgcg ctgcgcacat gtgctcggcg gggctggcgg     1620

gcgtcatcaa ccgcatgcgc gagagccgca gcgaggacgt aatgcgcatc actgtgggcg     1680

tggatggctc cgtgtacaag ctgcacccca gcttcaagga gcggttccat gccagcgtgc     1740

gcaggctgac gcccagctgc gagatcacct tcatcgagtc ggaggagggc agtggccggg     1800

gcgcggccct ggtctcggcg gtggcctgta agaaggcctg tatgctgggc cagtgagagc     1860

agtggccgca agcgcaggga ggatgccaca gccccacagc acccaggctc catggggaag     1920

tgctccccac acgtgctcgc agcctggcgg ggcaggaggc ctggccttgt caggacccag     1980

gccgcctgcc ataccgctgg ggaacagagc gggcctcttc cctcagtttt tcggtgggac     2040

agccccaggg ccctaacggg ggtgcggcag gagcaggaac agagactctg gaagcccccc     2100

acctttctcg ctggaatcaa tttcccagaa gggagttgct cactcaggac tttgatgcat     2160

ttccacactg tcagagctgt tggcctcgcc tgggcccagg ctctgggaag gggtgccctc     2220

tggatcctgc tgtggcctca cttccctggg aactcatcct gtgtggggag gcagctccaa     2280

cagcttgacc agacctagac ctgggccaaa agggcaggcc aggggctgct catcacccag     2340

tcctggccat tttcttgcct gaggctcaag aggcccaggg agcaatggga gggggctcca     2400

tggaggaggt gtcccaagct ttgaataccc cccagagacc ttttctctcc cataccatca     2460

ctgagtggct tgtgattctg ggatggaccc tcgcagcagg tgcaagagac agagccccca     2520

agcctctgcc ccaaggggcc cacaaagggg agaagggcca gccctacatc ttcagctccc     2580

atagcgctgg ctcaggaaga aaccccaagc agcattcagc acaccccaag ggacaacccc     2640

atcatatgac atgccaccct ctccatgccc aacctaagat tgtgtgggtt ttttaattaa     2700

aaatgttaaa agttttaaac atgaaaaaaa a                                    2731


<210>  6
<211>  2731
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Secuencia nucleotdica que codifica para la SEQ ID NO: 1 
       (variante de la invencin GCK-S64F)

<400>  6
ccgagcggcg cctgagcccc agggaagcag gctaggatgt gagagacaca gtcacctgca       60

gcctaattac tcaaaagctg tccccaggtc acagaaggga gaggacattt cccactgaat      120

ctgtctgaag gacactaagc cccacagctc aacacaacca ggagagaaag cgctgaggac      180

gccacccaag tgcccagcaa tggccctgcc tggagaacat ccaggctcag tgaggaaggg      240

tccagaaggg aatgcttgcc gactcgttgg agaacaatga aaaggaggaa actgtgactg      300

aacctcaaac cccaaaccag cccgaggaga accacattct cccagggacc cagggcgggc      360

cgtgacccct gcggcggaga agccttggat atttccactt cagaagccta ctggggaagg      420

ctgaggggtc ccagctcccc acgctggctg ctgtgcagat gctggacgac agagccagga      480

tggaggccgc caagaaggag aaggtagagc agatcctggc agagttccag ctgcaggagg      540

aggacctgaa gaaggtgatg agacggatgc agaaggagat ggaccgcggc ctgaggctgg      600

agacccatga agaggccagt gtgaagatgc tgcccaccta cgtgcgctcc accccagaag      660

gctcagaagt cggggacttc ctctccctgg acctgggtgg cactaacttc agggtgatgc      720

tggtgaaggt gggagaaggt gaggaggggc agtggagcgt gaagaccaaa caccagatgt      780

actccatccc cgaggacgcc atgaccggca ctgctgagat gctcttcgac tacatctctg      840

agtgcatctc cgacttcctg gacaagcatc agatgaaaca caagaagctg cccctgggct      900

tcaccttctc ctttcctgtg aggcacgaag acatcgataa gggcatcctt ctcaactgga      960

ccaagggctt caaggcctca ggagcagaag ggaacaatgt cgtggggctt ctgcgagacg     1020

ctatcaaacg gagaggggac tttgaaatgg atgtggtggc aatggtgaat gacacggtgg     1080

ccacgatgat ctcctgctac tacgaagacc atcagtgcga ggtcggcatg atcgtgggca     1140

cgggctgcaa tgcctgctac atggaggaga tgcagaatgt ggagctggtg gagggggacg     1200

agggccgcat gtgcgtcaat accgagtggg gcgccttcgg ggactccggc gagctggacg     1260

agttcctgct ggagtatgac cgcctggtgg acgagagctc tgcaaacccc ggtcagcagc     1320

tgtatgagaa gctcataggt ggcaagtaca tgggcgagct ggtgcggctt gtgctgctca     1380

ggctcgtgga cgaaaacctg ctcttccacg gggaggcctc cgagcagctg cgcacacgcg     1440

gagccttcga gacgcgcttc gtgtcgcagg tggagagcga cacgggcgac cgcaagcaga     1500

tctacaacat cctgagcacg ctggggctgc gaccctcgac caccgactgc gacatcgtgc     1560

gccgcgcctg cgagagcgtg tctacgcgcg ctgcgcacat gtgctcggcg gggctggcgg     1620

gcgtcatcaa ccgcatgcgc gagagccgca gcgaggacgt aatgcgcatc actgtgggcg     1680

tggatggctc cgtgtacaag ctgcacccca gcttcaagga gcggttccat gccagcgtgc     1740

gcaggctgac gcccagctgc gagatcacct tcatcgagtc ggaggagggc agtggccggg     1800

gcgcggccct ggtctcggcg gtggcctgta agaaggcctg tatgctgggc cagtgagagc     1860

agtggccgca agcgcaggga ggatgccaca gccccacagc acccaggctc catggggaag     1920

tgctccccac acgtgctcgc agcctggcgg ggcaggaggc ctggccttgt caggacccag     1980

gccgcctgcc ataccgctgg ggaacagagc gggcctcttc cctcagtttt tcggtgggac     2040

agccccaggg ccctaacggg ggtgcggcag gagcaggaac agagactctg gaagcccccc     2100

acctttctcg ctggaatcaa tttcccagaa gggagttgct cactcaggac tttgatgcat     2160

ttccacactg tcagagctgt tggcctcgcc tgggcccagg ctctgggaag gggtgccctc     2220

tggatcctgc tgtggcctca cttccctggg aactcatcct gtgtggggag gcagctccaa     2280

cagcttgacc agacctagac ctgggccaaa agggcaggcc aggggctgct catcacccag     2340

tcctggccat tttcttgcct gaggctcaag aggcccaggg agcaatggga gggggctcca     2400

tggaggaggt gtcccaagct ttgaataccc cccagagacc ttttctctcc cataccatca     2460

ctgagtggct tgtgattctg ggatggaccc tcgcagcagg tgcaagagac agagccccca     2520

agcctctgcc ccaaggggcc cacaaagggg agaagggcca gccctacatc ttcagctccc     2580

atagcgctgg ctcaggaaga aaccccaagc agcattcagc acaccccaag ggacaacccc     2640

atcatatgac atgccaccct ctccatgccc aacctaagat tgtgtgggtt ttttaattaa     2700

aaatgttaaa agttttaaac atgaaaaaaa a                                    2731


<210>  7
<211>  46
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador directo para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 3

<400>  7
gtggccacga tgatctcctg ctgctacgaa gaccatcagt gcgagg                      46


<210>  8
<211>  46
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador inverso para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 3

<400>  8
cctcgcactg atggtcttcg tagcagcagg agatcatcgt ggccac                      46


<210>  9
<211>  46
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador directo para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 2

<400>  9
cagggtgatg ctggtgaagt tgggagaagg tgaggagggg cagtgg                      46


<210>  10
<211>  46
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador inverso para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 2

<400>  10
ccactgcccc tcctcacctt ctcccaactt caccagcatc accctg                      46


<210>  11
<211>  45
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador directo para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 15

<400>  11
gagatcacct tcatcgagtc gaaggagggc agtggccggg gcgcg                       45


<210>  12
<211>  45
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador inverso para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 15

<400>  12
cgcgccccgg ccactgccct ccttcgactc gatgaaggtg atctc                       45


<210>  13
<211>  45
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador directo para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 16

<400>  13
gctgcgagat caccttcatc ggatcggagg agggcagtgg ccggg                       45


<210>  14
<211>  45
<212>  DNA
<213>  Secuencia Artificial

<220>
<223>  Cebador inverso para amplificar la SEQ ID NO: 5 y obtener la 
       secuencia nucleotdica que codifica para la SEQ ID NO: 16

<400>  14
cccggccact gccctcctcc gatccgatga aggtgatctc gcagc                       45


<210>  15
<211>  465
<212>  PRT
<213>  Secuencia Artificial

<220>
<223>  Variante de la invencin GCK-E442K

<400>  15

Met Leu Asp Asp Arg Ala Arg Met Glu Ala Ala Lys Lys Glu Lys Val 
1               5                   10                  15      


Glu Gln Ile Leu Ala Glu Phe Gln Leu Gln Glu Glu Asp Leu Lys Lys 
            20                  25                  30          


Val Met Arg Arg Met Gln Lys Glu Met Asp Arg Gly Leu Arg Leu Glu 
        35                  40                  45              


Thr His Glu Glu Ala Ser Val Lys Met Leu Pro Thr Tyr Val Arg Ser 
    50                  55                  60                  


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


Gly Thr Asn Phe Arg Val Met Leu Val Lys Val Gly Glu Gly Glu Glu 
                85                  90                  95      


Gly Gln Trp Ser Val Lys Thr Lys His Gln Met Tyr Ser Ile Pro Glu 
            100                 105                 110         


Asp Ala Met Thr Gly Thr Ala Glu Met Leu Phe Asp Tyr Ile Ser Glu 
        115                 120                 125             


Cys Ile Ser Asp Phe Leu Asp Lys His Gln Met Lys His Lys Lys Leu 
    130                 135                 140                 


Pro Leu Gly Phe Thr Phe Ser Phe Pro Val Arg His Glu Asp Ile Asp 
145                 150                 155                 160 


Lys Gly Ile Leu Leu Asn Trp Thr Lys Gly Phe Lys Ala Ser Gly Ala 
                165                 170                 175     


Glu Gly Asn Asn Val Val Gly Leu Leu Arg Asp Ala Ile Lys Arg Arg 
            180                 185                 190         


Gly Asp Phe Glu Met Asp Val Val Ala Met Val Asn Asp Thr Val Ala 
        195                 200                 205             


Thr Met Ile Ser Cys Tyr Tyr Glu Asp His Gln Cys Glu Val Gly Met 
    210                 215                 220                 


Ile Val Gly Thr Gly Cys Asn Ala Cys Tyr Met Glu Glu Met Gln Asn 
225                 230                 235                 240 


Val Glu Leu Val Glu Gly Asp Glu Gly Arg Met Cys Val Asn Thr Glu 
                245                 250                 255     


Trp Gly Ala Phe Gly Asp Ser Gly Glu Leu Asp Glu Phe Leu Leu Glu 
            260                 265                 270         


Tyr Asp Arg Leu Val Asp Glu Ser Ser Ala Asn Pro Gly Gln Gln Leu 
        275                 280                 285             


Tyr Glu Lys Leu Ile Gly Gly Lys Tyr Met Gly Glu Leu Val Arg Leu 
    290                 295                 300                 


Val Leu Leu Arg Leu Val Asp Glu Asn Leu Leu Phe His Gly Glu Ala 
305                 310                 315                 320 


Ser Glu Gln Leu Arg Thr Arg Gly Ala Phe Glu Thr Arg Phe Val Ser 
                325                 330                 335     


Gln Val Glu Ser Asp Thr Gly Asp Arg Lys Gln Ile Tyr Asn Ile Leu 
            340                 345                 350         


Ser Thr Leu Gly Leu Arg Pro Ser Thr Thr Asp Cys Asp Ile Val Arg 
        355                 360                 365             


Arg Ala Cys Glu Ser Val Ser Thr Arg Ala Ala His Met Cys Ser Ala 
    370                 375                 380                 


Gly Leu Ala Gly Val Ile Asn Arg Met Arg Glu Ser Arg Ser Glu Asp 
385                 390                 395                 400 


Val Met Arg Ile Thr Val Gly Val Asp Gly Ser Val Tyr Lys Leu His 
                405                 410                 415     


Pro Ser Phe Lys Glu Arg Phe His Ala Ser Val Arg Arg Leu Thr Pro 
            420                 425                 430         


Ser Cys Glu Ile Thr Phe Ile Glu Ser Lys Glu Gly Ser Gly Arg Gly 
        435                 440                 445             


Ala Ala Leu Val Ser Ala Val Ala Cys Lys Lys Ala Cys Met Leu Gly 
    450                 455                 460                 


Gln 
465 


<210>  16
<211>  465
<212>  PRT
<213>  Secuencia Artificial

<220>
<223>  Variante GCK-E440G

<400>  16

Met Leu Asp Asp Arg Ala Arg Met Glu Ala Ala Lys Lys Glu Lys Val 
1               5                   10                  15      


Glu Gln Ile Leu Ala Glu Phe Gln Leu Gln Glu Glu Asp Leu Lys Lys 
            20                  25                  30          


Val Met Arg Arg Met Gln Lys Glu Met Asp Arg Gly Leu Arg Leu Glu 
        35                  40                  45              


Thr His Glu Glu Ala Ser Val Lys Met Leu Pro Thr Tyr Val Arg Ser 
    50                  55                  60                  


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


Gly Thr Asn Phe Arg Val Met Leu Val Lys Val Gly Glu Gly Glu Glu 
                85                  90                  95      


Gly Gln Trp Ser Val Lys Thr Lys His Gln Met Tyr Ser Ile Pro Glu 
            100                 105                 110         


Asp Ala Met Thr Gly Thr Ala Glu Met Leu Phe Asp Tyr Ile Ser Glu 
        115                 120                 125             


Cys Ile Ser Asp Phe Leu Asp Lys His Gln Met Lys His Lys Lys Leu 
    130                 135                 140                 


Pro Leu Gly Phe Thr Phe Ser Phe Pro Val Arg His Glu Asp Ile Asp 
145                 150                 155                 160 


Lys Gly Ile Leu Leu Asn Trp Thr Lys Gly Phe Lys Ala Ser Gly Ala 
                165                 170                 175     


Glu Gly Asn Asn Val Val Gly Leu Leu Arg Asp Ala Ile Lys Arg Arg 
            180                 185                 190         


Gly Asp Phe Glu Met Asp Val Val Ala Met Val Asn Asp Thr Val Ala 
        195                 200                 205             


Thr Met Ile Ser Cys Tyr Tyr Glu Asp His Gln Cys Glu Val Gly Met 
    210                 215                 220                 


Ile Val Gly Thr Gly Cys Asn Ala Cys Tyr Met Glu Glu Met Gln Asn 
225                 230                 235                 240 


Val Glu Leu Val Glu Gly Asp Glu Gly Arg Met Cys Val Asn Thr Glu 
                245                 250                 255     


Trp Gly Ala Phe Gly Asp Ser Gly Glu Leu Asp Glu Phe Leu Leu Glu 
            260                 265                 270         


Tyr Asp Arg Leu Val Asp Glu Ser Ser Ala Asn Pro Gly Gln Gln Leu 
        275                 280                 285             


Tyr Glu Lys Leu Ile Gly Gly Lys Tyr Met Gly Glu Leu Val Arg Leu 
    290                 295                 300                 


Val Leu Leu Arg Leu Val Asp Glu Asn Leu Leu Phe His Gly Glu Ala 
305                 310                 315                 320 


Ser Glu Gln Leu Arg Thr Arg Gly Ala Phe Glu Thr Arg Phe Val Ser 
                325                 330                 335     


Gln Val Glu Ser Asp Thr Gly Asp Arg Lys Gln Ile Tyr Asn Ile Leu 
            340                 345                 350         


Ser Thr Leu Gly Leu Arg Pro Ser Thr Thr Asp Cys Asp Ile Val Arg 
        355                 360                 365             


Arg Ala Cys Glu Ser Val Ser Thr Arg Ala Ala His Met Cys Ser Ala 
    370                 375                 380                 


Gly Leu Ala Gly Val Ile Asn Arg Met Arg Glu Ser Arg Ser Glu Asp 
385                 390                 395                 400 


Val Met Arg Ile Thr Val Gly Val Asp Gly Ser Val Tyr Lys Leu His 
                405                 410                 415     


Pro Ser Phe Lys Glu Arg Phe His Ala Ser Val Arg Arg Leu Thr Pro 
            420                 425                 430         


Ser Cys Glu Ile Thr Phe Ile Gly Ser Glu Glu Gly Ser Gly Arg Gly 
        435                 440                 445             


Ala Ala Leu Val Ser Ala Val Ala Cys Lys Lys Ala Cys Met Leu Gly 
    450                 455                 460                 


Gln 
465 


