                         SEQUENCE LISTING

<110>  Council of Scientific and Industrial Research
       Joshi, Kishore
       Sahni, Girish
 
<120>  GENETICALLY MODIFIED YEAST CELL AND IMPROVED PROCESS FOR 
       PRODUCTION OF CLOT-SPECIFIC STREPTOKINASE

<130>  P31527

<160>  33    

<170>  PatentIn version 3.5

<210>  1
<211>  620
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK amino acid

<400>  1

Met Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu Lys Cys Phe Asp 
1               5                   10                  15      


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


Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser 
        35                  40                  45              


Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr 
    50                  55                  60                  


Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg 
65                  70                  75                  80  


Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp 
                85                  90                  95      


Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly 
            100                 105                 110         


Pro Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp Leu Leu Asp Arg 
        115                 120                 125             


Pro Ser Val Asn Asn Ser Gln Leu Val Val Ser Val Ala Gly Thr Val 
    130                 135                 140                 


Glu Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe Glu Ile Asp Leu 
145                 150                 155                 160 


Thr Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln Gly Leu Ser Pro 
                165                 170                 175     


Lys Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met Ser His Lys Leu 
            180                 185                 190         


Glu Lys Ala Asp Leu Leu Lys Ala Ile Gln Glu Gln Leu Ile Ala Asn 
        195                 200                 205             


Val His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp Phe Ala Ser Asp 
    210                 215                 220                 


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


Gly Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu Phe Leu Leu Ser 
                245                 250                 255     


Gly His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro Ile Gln Asn Gln 
            260                 265                 270         


Ala Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe Thr Pro Leu Asn 
        275                 280                 285             


Pro Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr Lys Leu Leu Lys 
    290                 295                 300                 


Thr Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu Leu Leu Ala Gln 
305                 310                 315                 320 


Ala Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr Thr Ile Tyr Glu 
                325                 330                 335     


Arg Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile Phe Arg Thr Ile 
            340                 345                 350         


Leu Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys Asn Arg Glu Gln 
        355                 360                 365             


Ala Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu Glu Ile Asn Asn 
    370                 375                 380                 


Thr Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys Lys Gly Glu Lys 
385                 390                 395                 400 


Pro Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu Phe Thr Ile Lys 
                405                 410                 415     


Tyr Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser Glu Gln Leu Leu 
            420                 425                 430         


Thr Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu Tyr Asp Pro Arg 
        435                 440                 445             


Asp Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala Phe Gly Ile Met 
    450                 455                 460                 


Asp Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His Asp Asp Thr Asn 
465                 470                 475                 480 


Arg Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu Gly Glu Asn Ala 
                485                 490                 495     


Ser Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln Ile Val Pro Ile 
            500                 505                 510         


Ala Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly 
        515                 520                 525             


Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr 
    530                 535                 540                 


Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg 
545                 550                 555                 560 


Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp 
                565                 570                 575     


Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly 
            580                 585                 590         


Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr 
        595                 600                 605             


Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    610                 615                 620 


<210>  2
<211>  1860
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CSSK nucleuic acid

<400>  2
gtgcaagctc aacaaattgt gcccatagct gagaagtgtt ttgatcatgc tgctgggact       60

tcctatttgg tcggagaaac gtgggagaag ccctaccaag gctggatgat ggtagattgt      120

acttgcctgg gagaaggcag cggacgcatc acttgcactt ctagaaatag atgcaacgat      180

caggacacaa ggacatccta tagaattgga gacacctgga gcaagaagga taatcgagga      240

aacctgctcc agtgcatctg cacaggcaac ggccgaggag agtggaagtg tgagaggcac      300

acctctgtgc agaccacatc gagcggatct ggccccttca ccgatgttcg tattgctgga      360

cctgagtggc tgctagaccg tccatctgtc aacaacagcc aattagttgt tagcgttgct      420

ggtactgttg aggggacgaa tcaagacatt agtcttaaat tttttgaaat cgatctaaca      480

tcacgacctg ctcatggagg aaagacagag caaggcttaa gtccaaaatc aaaaccattt      540

gctactgata gtggcgcgat gtcacataaa cttgagaaag ctgacttact aaaggctatt      600

caagaacaat tgatcgctaa cgtccacagt aacgacgact actttgaggt cattgatttt      660

gcaagcgatg caaccattac tgatccaaac ggcaaggtct actttgctga caaagatggt      720

tcggtaacct tgccgaccca acctgtccaa gaatttttgc taagcggaca tgtgcgcgtt      780

agaccatata aagaaaaacc aatacaaaac caagcgaaat ctgttgatgt ggaatatact      840

gtacagttta ctcccttaaa ccctgatgac gatttcagac caggtctcaa agatactaag      900

ctattgaaaa cactagctat cggtgacacc atcacatctc aagaattact agctcaagca      960

caaagcattt taaacaaaaa ccacccaggc tatacgattt atgaacgtga ctcctcaatc     1020

gtcactcatg acaatgacat tttccgtacg attttaccaa tggatcaaga gttatcttac     1080

cgtgttaaaa atcgggaaca agcttatagg atcaataaaa aatctggtct gaatgaagaa     1140

ataaacaaca ctgacctgat ctctgagaaa tattacgtcc ttaaaaaagg ggaaaagccg     1200

tatgatccct ttgatcgcag tcacttgaaa ctgttcacca tcaaatacgt tgatgtcgat     1260

accaacgaat tgctaaaaag tgagcagctc ttaacagcta gcgaacgtaa cttagacttc     1320

agagatttat acgatcctcg tgataaggct aaactactct acaacaatct cgatgctttt     1380

ggtattatgg actatacctt aactggaaaa gtagaggata atcacgatga caccaaccgt     1440

atcataaccg tttatatggg caagcgaccc gaaggagaga atgctagcta tcatttagcc     1500

ggtggcggac aagctcaaca aattgtgccc atagctgaga agtgttttga tcatgctgct     1560

gggacttcct atttggtcgg agaaacgtgg gagaagccct accaaggctg gatgatggta     1620

gattgtactt gcctgggaga aggcagcgga cgcatcactt gcacttctag aaatagatgc     1680

aacgatcagg acacaaggac atcctataga attggagaca cctggagcaa gaaggataat     1740

cgaggaaacc tgctccagtg catctgcaca ggcaacggcc gaggagagtg gaagtgtgag     1800

aggcacacct ctgtgcagac cacatcgagc ggatctggcc ccttcaccga tgttcgttag     1860


<210>  3
<211>  619
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK sequences modified for Pichia

<400>  3

Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His 
1               5                   10                  15      


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


Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly 
        35                  40                  45              


Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg 
    50                  55                  60                  


Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly 
65                  70                  75                  80  


Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys 
                85                  90                  95      


Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro 
            100                 105                 110         


Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp Leu Leu Asp Arg Pro 
        115                 120                 125             


Ser Val Asn Asn Ser Gln Leu Val Val Ser Val Ala Gly Thr Val Glu 
    130                 135                 140                 


Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe Glu Ile Asp Leu Thr 
145                 150                 155                 160 


Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln Gly Leu Ser Pro Lys 
                165                 170                 175     


Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met Ser His Lys Leu Glu 
            180                 185                 190         


Lys Ala Asp Leu Leu Lys Ala Ile Gln Glu Gln Leu Ile Ala Asn Val 
        195                 200                 205             


His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp Phe Ala Ser Asp Ala 
    210                 215                 220                 


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


Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu Phe Leu Leu Ser Gly 
                245                 250                 255     


His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro Ile Gln Asn Gln Ala 
            260                 265                 270         


Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe Thr Pro Leu Asn Pro 
        275                 280                 285             


Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr Lys Leu Leu Lys Thr 
    290                 295                 300                 


Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu Leu Leu Ala Gln Ala 
305                 310                 315                 320 


Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr Thr Ile Tyr Glu Arg 
                325                 330                 335     


Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile Phe Arg Thr Ile Leu 
            340                 345                 350         


Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys Asn Arg Glu Gln Ala 
        355                 360                 365             


Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu Glu Ile Asn Asn Thr 
    370                 375                 380                 


Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys Lys Gly Glu Lys Pro 
385                 390                 395                 400 


Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu Phe Thr Ile Lys Tyr 
                405                 410                 415     


Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser Glu Gln Leu Leu Thr 
            420                 425                 430         


Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu Tyr Asp Pro Arg Asp 
        435                 440                 445             


Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala Phe Gly Ile Met Asp 
    450                 455                 460                 


Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His Asp Asp Thr Asn Arg 
465                 470                 475                 480 


Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu Gly Glu Asn Ala Ser 
                485                 490                 495     


Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln Ile Val Pro Ile Ala 
            500                 505                 510         


Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu 
        515                 520                 525             


Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys 
    530                 535                 540                 


Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys 
545                 550                 555                 560 


Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser 
                565                 570                 575     


Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn 
            580                 585                 590         


Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr 
        595                 600                 605             


Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    610                 615                 


<210>  4
<211>  1860
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CSSK sequence modified for Pichia

<400>  4
gttcaagccc agcagattgt tccaatcgct gagaagtgtt tcgatcacgc tgctggtact       60

tcatacttgg tcggtgaaac ctgggaaaag ccataccagg gatggatgat ggttgactgc      120

acctgtttag gtgaaggttc cggtagaatc acctgtacct ccagaaacag atgtaacgac      180

caggacacca gaacctctta cagaatcggt gatacctggt ccaagaagga caacagaggt      240

aacctgttgc agtgtatctg taccggtaac ggtcgtggag aatggaagtg cgagagacac      300

acttccgttc aaactacttc ttccggttcc ggtccattca ctgatgttag aatcgctggt      360

ccagaatggt tgttggacag accatccgtt aacaactccc agttggttgt ttctgttgct      420

ggtactgttg agggaactaa ccaggacatc tccttgaagt tcttcgagat cgacttgact      480

tctagaccag ctcatggtgg aaagactgag caaggcttaa gtccaaagtc caagccattc      540

gctactgatt ctggtgctat gtcccacaag ttggagaagg ctgacttgtt gaaggctatc      600

caagagcagt tgatcgctaa cgttcactct aacgacgact acttcgaggt tatcgacttc      660

gcttccgacg ctactattac tgacccaaac ggaaaggttt acttcgctga caaggacggt      720

tctgttactt tgccaactca gccagttcaa gagttcttgt tgtccggtca tgttagagtt      780

agaccataca aagagaagcc aatccagaac caggctaagt ctgttgacgt tgagtacact      840

gttcagttca ctccattgaa cccagatgac gactttagac caggattgaa ggacactaag      900

ttgttgaaaa ctttggctat cggtgacact attacttccc aagagttgtt ggctcaagct      960

cagtccatct tgaacaagaa ccacccaggt tacactatct acgagagaga ctcctccatt     1020

gttactcacg acaacgacat cttcagaact atcttgccaa tggaccaaga gttgtcctac     1080

agagttaaga acagagagca ggcttacaga atcaacaaga agtccggatt gaacgaagag     1140

atcaacaaca ctgacttgat ctccgagaag tactacgttt tgaagaaggg tgaaaagcca     1200

tacgatccat tcgacagatc ccacttgaag ttgttcacta tcaagtacgt tgacgttgac     1260

actaacgagt tgttgaagtc cgagcagttg ttgactgctt ccgagagaaa cttggacttc     1320

agagacttgt acgacccaag agacaaggct aaattgttgt acaataactt ggacgctttc     1380

ggtatcatgg actacacttt gactggaaag gttgaggata accacgacga cactaacaga     1440

atcatcactg tttacatggg taaaagacca gagggtgaaa acgcttctta ccacttggct     1500

ggaggtggtc aagctcaaca aatcgtccct atcgccgaaa agtgttttga ccatgccgct     1560

ggtactagtt acctggtggg tgaaacttgg gagaaacctt atcaaggatg gatgatggtc     1620

gattgtactt gtttgggaga gggatccggt agaattactt gcaccagtag aaacagatgc     1680

aatgatcaag atactagaac ttcctacaga attggtgaca cttggagtaa gaaggataat     1740

agaggtaatc ttctgcaatg catctgcact ggaaacggaa ggggtgagtg gaaatgcgaa     1800

agacatacct ctgttcagac tacctcttct ggttctggac ccttcaccga tgtcagatag     1860


<210>  5
<211>  619
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK modified N-terminal original C-terminal

<400>  5

Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His 
1               5                   10                  15      


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


Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly 
        35                  40                  45              


Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg 
    50                  55                  60                  


Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly 
65                  70                  75                  80  


Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys 
                85                  90                  95      


Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro 
            100                 105                 110         


Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp Leu Leu Asp Arg Pro 
        115                 120                 125             


Ser Val Asn Asn Ser Gln Leu Val Val Ser Val Ala Gly Thr Val Glu 
    130                 135                 140                 


Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe Glu Ile Asp Leu Thr 
145                 150                 155                 160 


Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln Gly Leu Ser Pro Lys 
                165                 170                 175     


Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met Ser His Lys Leu Glu 
            180                 185                 190         


Lys Ala Asp Leu Leu Lys Ala Ile Gln Glu Gln Leu Ile Ala Asn Val 
        195                 200                 205             


His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp Phe Ala Ser Asp Ala 
    210                 215                 220                 


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


Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu Phe Leu Leu Ser Gly 
                245                 250                 255     


His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro Ile Gln Asn Gln Ala 
            260                 265                 270         


Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe Thr Pro Leu Asn Pro 
        275                 280                 285             


Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr Lys Leu Leu Lys Thr 
    290                 295                 300                 


Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu Leu Leu Ala Gln Ala 
305                 310                 315                 320 


Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr Thr Ile Tyr Glu Arg 
                325                 330                 335     


Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile Phe Arg Thr Ile Leu 
            340                 345                 350         


Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys Asn Arg Glu Gln Ala 
        355                 360                 365             


Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu Glu Ile Asn Asn Thr 
    370                 375                 380                 


Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys Lys Gly Glu Lys Pro 
385                 390                 395                 400 


Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu Phe Thr Ile Lys Tyr 
                405                 410                 415     


Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser Glu Gln Leu Leu Thr 
            420                 425                 430         


Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu Tyr Asp Pro Arg Asp 
        435                 440                 445             


Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala Phe Gly Ile Met Asp 
    450                 455                 460                 


Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His Asp Asp Thr Asn Arg 
465                 470                 475                 480 


Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu Gly Glu Asn Ala Ser 
                485                 490                 495     


Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln Ile Val Pro Ile Ala 
            500                 505                 510         


Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu 
        515                 520                 525             


Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys 
    530                 535                 540                 


Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys 
545                 550                 555                 560 


Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser 
                565                 570                 575     


Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn 
            580                 585                 590         


Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr 
        595                 600                 605             


Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    610                 615                 


<210>  6
<211>  1860
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CSSK modified 5' original 3'

<400>  6
gttcaagccc agcagattgt tccaatcgct gagaagtgtt tcgatcacgc tgctggtact       60

tcatacttgg tcggtgaaac ctgggaaaag ccataccagg gatggatgat ggttgactgc      120

acctgtttag gtgaaggttc cggtagaatc acctgtacct ccagaaacag atgtaacgac      180

caggacacca gaacctctta cagaatcggt gatacctggt ccaagaagga caacagaggt      240

aacctgttgc agtgtatctg taccggtaac ggtcgtggag aatggaagtg cgagagacac      300

acttccgttc aaactacttc ttccggttcc ggtccattca ctgatgttag aatcgctggt      360

ccagaatggt tgttggacag accatccgtt aacaactccc agttggttgt ttctgttgct      420

ggtactgttg agggaactaa ccaggacatc tccttgaagt tcttcgagat cgacttgact      480

tctagaccag ctcatggtgg aaagactgag caaggcttaa gtccaaaatc aaaaccattt      540

gctactgata gtggcgcgat gtcacataaa cttgagaaag ctgacttact aaaggctatt      600

caagaacaat tgatcgctaa cgtccacagt aacgacgact actttgaggt cattgatttt      660

gcaagcgatg caaccattac tgatccaaac ggcaaggtct actttgctga caaagatggt      720

tcggtaacct tgccgaccca acctgtccaa gaatttttgc taagcggaca tgtgcgcgtt      780

agaccatata aagaaaaacc aatacaaaac caagcgaaat ctgttgatgt ggaatatact      840

gtacagttta ctcccttaaa ccctgatgac gatttcagac caggtctcaa agatactaag      900

ctattgaaaa cactagctat cggtgacacc atcacatctc aagaattact agctcaagca      960

caaagcattt taaacaaaaa ccacccaggc tatacgattt atgaacgtga ctcctcaatc     1020

gtcactcatg acaatgacat tttccgtacg attttaccaa tggatcaaga gttatcttac     1080

cgtgttaaaa atcgggaaca agcttatagg atcaataaaa aatctggtct gaatgaagaa     1140

ataaacaaca ctgacctgat ctctgagaaa tattacgtcc ttaaaaaagg ggaaaagccg     1200

tatgatccct ttgatcgcag tcacttgaaa ctgttcacca tcaaatacgt tgatgtcgat     1260

accaacgaat tgctaaaaag tgagcagctc ttaacagcta gcgaacgtaa cttagacttc     1320

agagatttat acgatcctcg tgataaggct aaactactct acaacaatct cgatgctttt     1380

ggtattatgg actatacctt aactggaaaa gtagaggata atcacgatga caccaaccgt     1440

atcataaccg tttatatggg caagcgaccc gaaggagaga atgctagcta tcatttagcc     1500

ggtggcggac aagctcaaca aattgtgccc atagctgaga agtgttttga tcatgctgct     1560

gggacttcct atttggtcgg agaaacgtgg gagaagccct accaaggctg gatgatggta     1620

gattgtactt gcctgggaga aggcagcgga cgcatcactt gcacttctag aaatagatgc     1680

aacgatcagg acacaaggac atcctataga attggagaca cctggagcaa gaaggataat     1740

cgaggaaacc tgctccagtg catctgcaca ggcaacggcc gaggagagtg gaagtgtgag     1800

aggcacacct ctgtgcagac cacatcgagc ggatctggcc ccttcaccga tgttcgttag     1860


<210>  7
<211>  619
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK original N-terminal modified C-terminal

<400>  7

Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His 
1               5                   10                  15      


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


Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly 
        35                  40                  45              


Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg 
    50                  55                  60                  


Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly 
65                  70                  75                  80  


Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys 
                85                  90                  95      


Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro 
            100                 105                 110         


Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp Leu Leu Asp Arg Pro 
        115                 120                 125             


Ser Val Asn Asn Ser Gln Leu Val Val Ser Val Ala Gly Thr Val Glu 
    130                 135                 140                 


Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe Glu Ile Asp Leu Thr 
145                 150                 155                 160 


Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln Gly Leu Ser Pro Lys 
                165                 170                 175     


Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met Ser His Lys Leu Glu 
            180                 185                 190         


Lys Ala Asp Leu Leu Lys Ala Ile Gln Glu Gln Leu Ile Ala Asn Val 
        195                 200                 205             


His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp Phe Ala Ser Asp Ala 
    210                 215                 220                 


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


Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu Phe Leu Leu Ser Gly 
                245                 250                 255     


His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro Ile Gln Asn Gln Ala 
            260                 265                 270         


Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe Thr Pro Leu Asn Pro 
        275                 280                 285             


Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr Lys Leu Leu Lys Thr 
    290                 295                 300                 


Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu Leu Leu Ala Gln Ala 
305                 310                 315                 320 


Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr Thr Ile Tyr Glu Arg 
                325                 330                 335     


Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile Phe Arg Thr Ile Leu 
            340                 345                 350         


Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys Asn Arg Glu Gln Ala 
        355                 360                 365             


Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu Glu Ile Asn Asn Thr 
    370                 375                 380                 


Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys Lys Gly Glu Lys Pro 
385                 390                 395                 400 


Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu Phe Thr Ile Lys Tyr 
                405                 410                 415     


Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser Glu Gln Leu Leu Thr 
            420                 425                 430         


Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu Tyr Asp Pro Arg Asp 
        435                 440                 445             


Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala Phe Gly Ile Met Asp 
    450                 455                 460                 


Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His Asp Asp Thr Asn Arg 
465                 470                 475                 480 


Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu Gly Glu Asn Ala Ser 
                485                 490                 495     


Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln Ile Val Pro Ile Ala 
            500                 505                 510         


Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu 
        515                 520                 525             


Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys 
    530                 535                 540                 


Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys 
545                 550                 555                 560 


Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser 
                565                 570                 575     


Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn 
            580                 585                 590         


Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr 
        595                 600                 605             


Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    610                 615                 


<210>  8
<211>  1860
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CSSK original 5' modified 3'

<400>  8
gtgcaagctc aacaaattgt gcccatagct gagaagtgtt ttgatcatgc tgctgggact       60

tcctatttgg tcggagaaac gtgggagaag ccctaccaag gctggatgat ggtagattgt      120

acttgcctgg gagaaggcag cggacgcatc acttgcactt ctagaaatag atgcaacgat      180

caggacacaa ggacatccta tagaattgga gacacctgga gcaagaagga taatcgagga      240

aacctgctcc agtgcatctg cacaggcaac ggccgaggag agtggaagtg tgagaggcac      300

acctctgtgc agaccacatc gagcggatct ggccccttca ccgatgttcg tattgctgga      360

cctgagtggc tgctagaccg tccatctgtc aacaacagcc aattagttgt tagcgttgct      420

ggtactgttg aggggacgaa tcaagacatt agtcttaaat tttttgaaat cgatctaaca      480

tcacgacctg ctcatggagg aaagacagag caaggcttaa gtccaaagtc caagccattc      540

gctactgatt ctggtgctat gtcccacaag ttggagaagg ctgacttgtt gaaggctatc      600

caagagcagt tgatcgctaa cgttcactct aacgacgact acttcgaggt tatcgacttc      660

gcttccgacg ctactattac tgacccaaac ggaaaggttt acttcgctga caaggacggt      720

tctgttactt tgccaactca gccagttcaa gagttcttgt tgtccggtca tgttagagtt      780

agaccataca aagagaagcc aatccagaac caggctaagt ctgttgacgt tgagtacact      840

gttcagttca ctccattgaa cccagatgac gactttagac caggattgaa ggacactaag      900

ttgttgaaaa ctttggctat cggtgacact attacttccc aagagttgtt ggctcaagct      960

cagtccatct tgaacaagaa ccacccaggt tacactatct acgagagaga ctcctccatt     1020

gttactcacg acaacgacat cttcagaact atcttgccaa tggaccaaga gttgtcctac     1080

agagttaaga acagagagca ggcttacaga atcaacaaga agtccggatt gaacgaagag     1140

atcaacaaca ctgacttgat ctccgagaag tactacgttt tgaagaaggg tgaaaagcca     1200

tacgatccat tcgacagatc ccacttgaag ttgttcacta tcaagtacgt tgacgttgac     1260

actaacgagt tgttgaagtc cgagcagttg ttgactgctt ccgagagaaa cttggacttc     1320

agagacttgt acgacccaag agacaaggct aaattgttgt acaataactt ggacgctttc     1380

ggtatcatgg actacacttt gactggaaag gttgaggata accacgacga cactaacaga     1440

atcatcactg tttacatggg taaaagacca gagggtgaaa acgcttctta ccacttggct     1500

ggaggtggtc aagctcaaca aatcgtccct atcgccgaaa agtgttttga ccatgccgct     1560

ggtactagtt acctggtggg tgaaacttgg gagaaacctt atcaaggatg gatgatggtc     1620

gattgtactt gtttgggaga gggatccggt agaattactt gcaccagtag aaacagatgc     1680

aatgatcaag atactagaac ttcctacaga attggtgaca cttggagtaa gaaggataat     1740

agaggtaatc ttctgcaatg catctgcact ggaaacggaa ggggtgagtg gaaatgcgaa     1800

agacatacct ctgttcagac tacctcttct ggttctggac ccttcaccga tgtcagatag     1860


<210>  9
<211>  85
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified Alpha Signal Sequence

<400>  9

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg 
                85  


<210>  10
<211>  255
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Modified alpha signal sequence

<400>  10
atgagatttc cttcaatttt tactgcagtt ttattcgcag catcctccgc attagctgct       60

ccagtcaaca ctacaacaga agatgaaacg gcacaaattc cggctgaagc tgtcatcggt      120

tactcagatt tagaagggga tttcgatgtt gctgttttgc cattttccaa cagcacaaat      180

aacgggttat tgtttataaa tactactatt gccagcattg ctgctaaaga agaaggggta      240

tctctcgaga aaaga                                                       255


<210>  11
<211>  414
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Streptokinase sequence

<400>  11

Ile Ala Gly Pro Glu Trp Leu Leu Asp Arg Pro Ser Val Asn Asn Ser 
1               5                   10                  15      


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


Ile Ser Leu Lys Phe Phe Glu Ile Asp Leu Thr Ser Arg Pro Ala His 
        35                  40                  45              


Gly Gly Lys Thr Glu Gln Gly Leu Ser Pro Lys Ser Lys Pro Phe Ala 
    50                  55                  60                  


Thr Asp Ser Gly Ala Met Ser His Lys Leu Glu Lys Ala Asp Leu Leu 
65                  70                  75                  80  


Lys Ala Ile Gln Glu Gln Leu Ile Ala Asn Val His Ser Asn Asp Asp 
                85                  90                  95      


Tyr Phe Glu Val Ile Asp Phe Ala Ser Asp Ala Thr Ile Thr Asp Arg 
            100                 105                 110         


Asn Gly Lys Val Tyr Phe Ala Asp Lys Asp Gly Ser Val Thr Leu Pro 
        115                 120                 125             


Thr Gln Pro Val Gln Glu Phe Leu Leu Ser Gly His Val Arg Val Arg 
    130                 135                 140                 


Pro Tyr Lys Glu Lys Pro Ile Gln Asn Gln Ala Lys Ser Val Asp Val 
145                 150                 155                 160 


Glu Tyr Thr Val Gln Phe Thr Pro Leu Asn Pro Asp Asp Asp Phe Arg 
                165                 170                 175     


Pro Gly Leu Lys Asp Thr Lys Leu Leu Lys Thr Leu Ala Ile Gly Asp 
            180                 185                 190         


Thr Ile Thr Ser Gln Glu Leu Leu Ala Gln Ala Gln Ser Ile Leu Asn 
        195                 200                 205             


Lys Asn His Pro Gly Tyr Thr Ile Tyr Glu Arg Asp Ser Ser Ile Val 
    210                 215                 220                 


Thr His Asp Asn Asp Ile Phe Arg Thr Ile Leu Pro Met Asp Gln Glu 
225                 230                 235                 240 


Phe Thr Tyr Arg Val Lys Asn Arg Glu Gln Ala Tyr Arg Ile Asn Lys 
                245                 250                 255     


Lys Ser Gly Leu Asn Glu Glu Ile Asn Asn Thr Asp Leu Ile Ser Glu 
            260                 265                 270         


Lys Tyr Tyr Val Leu Lys Lys Gly Glu Lys Pro Tyr Asp Pro Phe Asp 
        275                 280                 285             


Arg Ser His Leu Lys Leu Phe Thr Ile Lys Tyr Val Asp Val Asp Thr 
    290                 295                 300                 


Asn Glu Leu Leu Lys Ser Glu Gln Leu Leu Thr Ala Ser Glu Arg Asn 
305                 310                 315                 320 


Leu Asp Phe Arg Asp Leu Tyr Asp Pro Arg Asp Lys Ala Lys Leu Leu 
                325                 330                 335     


Tyr Asn Asn Leu Asp Ala Phe Gly Ile Met Asp Tyr Thr Leu Thr Gly 
            340                 345                 350         


Lys Val Glu Asp Asn His Asp Asp Thr Asn Arg Ile Ile Thr Val Tyr 
        355                 360                 365             


Met Gly Lys Arg Pro Glu Gly Glu Asn Ala Ser Tyr His Leu Ala Tyr 
    370                 375                 380                 


Asp Lys Asp Arg Tyr Thr Glu Glu Glu Arg Glu Val Tyr Ser Tyr Leu 
385                 390                 395                 400 


Arg Tyr Thr Gly Thr Pro Ile Pro Asp Asn Pro Asn Asp Lys 
                405                 410                 


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

<220>
<223>  SK C-terminal equence with poly-glycine linder and 
       transglutaminase site

<400>  12

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


<210>  13
<211>  53
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  SK 3' sequence with poly-glycine liner and transglutaminase site

<400>  13
gaatgctagc taccatttag ctggtggtgg ccagtgcgca acagattgta ccc              53


<210>  14
<211>  99
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Native alpha signal sequence

<400>  14

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg Glu Ala Glu Ala Tyr Val Glu Phe Pro Arg Ala 
                85                  90                  95      


Ala Ala Asn 
            


<210>  15
<211>  300
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Native alpha signal sequence

<400>  15
atgagatttc cttcaatttt tactgcagtt ttattcgcag catcctccgc attagctgct       60

ccagtcaaca ctacaacaga agatgaaacg gcacaaattc cggctgaagc tgtcatcggt      120

tactcagatt tagaagggga tttcgatgtt gctgttttgc cattttccaa cagcacaaat      180

aacgggttat tgtttataaa tactactatt gccagcattg ctgctaaaga agaaggggta      240

tctctcgaga aaagagaggc tgaagcttac gtagaattcc ctagggcggc cgcgaattaa      300


<210>  16
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Signal peptide sequence stretch

<400>  16

Glu Lys Arg Glu Ala Glu Ala 
1               5           


<210>  17
<211>  594
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Partial vector sequence with AOX1 5' promoter and alpha sequence

<400>  17
ttatcatcat tattagctta cttcataatt gcgactggtt ccaattgaca agctttgatt       60

ttaacgactt ttaacgacaa cttgagaaga tcaaaaacaa ctaattattc gaaggatcca      120

aacgatgaga tttccttcaa tttttactgc aattttattc gcagcatcct ccgcattagc      180

tgctccagtc aacactacaa cagaagatga aacggcacaa attccggctg aagctgtcat      240

cggttactca satttagaag gggatttcga tgttgctgtt ttgccatttt ccaacagcac      300

aaataacggg ttattgttta taaatactac tattgccagc attgctgcta aagaagaagg      360

ggtatctctc gagaaaagag aggctgaagc ttacgtagaa ttccctaggg cggccgcgat      420

ttaattcgcc ttagacatga ctgttcctca gttcaagttg ggcacttacg agaagaccgg      480

tcttgctaga ttctaatcaa gaggatgtca gaatgccatt tcggtgagag atgcaggctt      540

catttttgat acttttttat ttgtaaccta tatagtatag gatttttttt gtga            594


<210>  18
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Partical vector sequence

<400>  18
ctcgagaaaa gagaggctga agcttacgta gaattcccta gggcggcctc                  50


<210>  19
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Polypeptide encoded by partial vector sequence

<400>  19

Glu Lys Arg Glu Ala Glu Ala Tyr Val Glu Phe Pro Arg 
1               5                   10              


<210>  20
<211>  97
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Alpha signal sequence plus N-terminal CSSK

<400>  20

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg Gln Ala Gln Gln Ile Val Pro Ile Ala Glu Lys 
                85                  90                  95      


Cys 
    


<210>  21
<211>  330
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Fibrin binding domains 4,5

<400>  21
cccatagctg agaagtgttt tgatcatgct gctgggactt cctatgtggt cggagaaacg       60

tgggagaagc cctaccaagg ctggatgatg gtagattgta cttgcctggg agaaggcagc      120

ggacgcatca cttgcacttc tagaaataga tgcaacgatc aggacacaag gacatcctat      180

agaattggag acacctggag caagaaggat aatcgaggaa acctgctcca gtgcatctgc      240

acaggcaacg gccgaggaga gtggaagtgt gagaggcaca cctctgtgca gaccacatcg      300

agcggatctg gccccttcac cgatgttcgt                                       330


<210>  22
<211>  110
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fibrin binding domains 4,5

<400>  22

Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Val 
1               5                   10                  15      


Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp 
            20                  25                  30          


Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg 
        35                  40                  45              


Asn Arg Cys Asn Asp Gln Asp Ser Arg Thr Ser Tyr Arg Ile Gly Asp 
    50                  55                  60                  


Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys 
65                  70                  75                  80  


Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val 
                85                  90                  95      


Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
            100                 105                 110 


<210>  23
<211>  2115
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CSSK sequence modified alpha sequence plus modified for Picha

<400>  23
atgagatttc cttcaatttt tactgcagtt ttattcgcag catcctccgc attagctgct       60

ccagtcaaca ctacaacaga agatgaaacg gcacaaattc cggctgaagc tgtcatcggt      120

tactcagatt tagaagggga tttcgatgtt gctgttttgc cattttccaa cagcacaaat      180

aacgggttat tgtttataaa tactactatt gccagcattg ctgctaaaga agaaggggta      240

tctctcgaga aaagagttca agcccagcag attgttccaa tcgctgagaa gtgtttcgat      300

cacgctgctg gtacttcata cttggtcggt gaaacctggg aaaagccata ccagggatgg      360

atgatggttg actgcacctg tttaggtgaa ggttccggta gaatcacctg tacctccaga      420

aacagatgta acgaccagga caccagaacc tcttacagaa tcggtgatac ctggtccaag      480

aaggacaaca gaggtaacct gttgcagtgt atctgtaccg gtaacggtcg tggagaatgg      540

aagtgcgaga gacacacttc cgttcaaact acttcttccg gttccggtcc attcactgat      600

gttagaatcg ctggtccaga atggttgttg gacagaccat ccgttaacaa ctcccagttg      660

gttgtttctg ttgctggtac tgttgaggga actaaccagg acatctcctt gaagttcttc      720

gagatcgact tgacttctag accagctcat ggtggaaaga ctgagcaagg cttaagtcca      780

aagtccaagc cattcgctac tgattctggt gctatgtccc acaagttgga gaaggctgac      840

ttgttgaagg ctatccaaga gcagttgatc gctaacgttc actctaacga cgactacttc      900

gaggttatcg acttcgcttc cgacgctact attactgacc caaacggaaa ggtttacttc      960

gctgacaagg acggttctgt tactttgcca actcagccag ttcaagagtt cttgttgtcc     1020

ggtcatgtta gagttagacc atacaaagag aagccaatcc agaaccaggc taagtctgtt     1080

gacgttgagt acactgttca gttcactcca ttgaacccag atgacgactt tagaccagga     1140

ttgaaggaca ctaagttgtt gaaaactttg gctatcggtg acactattac ttcccaagag     1200

ttgttggctc aagctcagtc catcttgaac aagaaccacc caggttacac tatctacgag     1260

agagactcct ccattgttac tcacgacaac gacatcttca gaactatctt gccaatggac     1320

caagagttgt cctacagagt taagaacaga gagcaggctt acagaatcaa caagaagtcc     1380

ggattgaacg aagagatcaa caacactgac ttgatctccg agaagtacta cgttttgaag     1440

aagggtgaaa agccatacga tccattcgac agatcccact tgaagttgtt cactatcaag     1500

tacgttgacg ttgacactaa cgagttgttg aagtccgagc agttgttgac tgcttccgag     1560

agaaacttgg acttcagaga cttgtacgac ccaagagaca aggctaaatt gttgtacaat     1620

aacttggacg ctttcggtat catggactac actttgactg gaaaggttga ggataaccac     1680

gacgacacta acagaatcat cactgtttac atgggtaaaa gaccagaggg tgaaaacgct     1740

tcttaccact tggctggagg tggtcaagct caacaaatcg tccctatcgc cgaaaagtgt     1800

tttgaccatg ccgctggtac tagttacctg gtgggtgaaa cttgggagaa accttatcaa     1860

ggatggatga tggtcgattg tacttgtttg ggagagggat ccggtagaat tacttgcacc     1920

agtagaaaca gatgcaatga tcaagatact agaacttcct acagaattgg tgacacttgg     1980

agtaagaagg ataatagagg taatcttctg caatgcatct gcactggaaa cggaaggggt     2040

gagtggaaat gcgaaagaca tacctctgtt cagactacct cttctggttc tggacccttc     2100

accgatgtca gatag                                                      2115


<210>  24
<211>  704
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK sequence modified alpha sequence plus modified for Pichia

<400>  24

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu 
                85                  90                  95      


Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu Thr 
            100                 105                 110         


Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu 
        115                 120                 125             


Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn 
    130                 135                 140                 


Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys 
145                 150                 155                 160 


Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly 
                165                 170                 175     


Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser 
            180                 185                 190         


Ser Gly Ser Gly Pro Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp 
        195                 200                 205             


Leu Leu Asp Arg Pro Ser Val Asn Asn Ser Gln Leu Val Val Ser Val 
    210                 215                 220                 


Ala Gly Thr Val Glu Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe 
225                 230                 235                 240 


Glu Ile Asp Leu Thr Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln 
                245                 250                 255     


Gly Leu Ser Pro Lys Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met 
            260                 265                 270         


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


Leu Ile Ala Asn Val His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp 
    290                 295                 300                 


Phe Ala Ser Asp Ala Thr Ile Thr Asp Pro Asn Gly Lys Val Tyr Phe 
305                 310                 315                 320 


Ala Asp Lys Asp Gly Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu 
                325                 330                 335     


Phe Leu Leu Ser Gly His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro 
            340                 345                 350         


Ile Gln Asn Gln Ala Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe 
        355                 360                 365             


Thr Pro Leu Asn Pro Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr 
    370                 375                 380                 


Lys Leu Leu Lys Thr Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu 
385                 390                 395                 400 


Leu Leu Ala Gln Ala Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr 
                405                 410                 415     


Thr Ile Tyr Glu Arg Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile 
            420                 425                 430         


Phe Arg Thr Ile Leu Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys 
        435                 440                 445             


Asn Arg Glu Gln Ala Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu 
    450                 455                 460                 


Glu Ile Asn Asn Thr Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys 
465                 470                 475                 480 


Lys Gly Glu Lys Pro Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu 
                485                 490                 495     


Phe Thr Ile Lys Tyr Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser 
            500                 505                 510         


Glu Gln Leu Leu Thr Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu 
        515                 520                 525             


Tyr Asp Pro Arg Asp Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala 
    530                 535                 540                 


Phe Gly Ile Met Asp Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His 
545                 550                 555                 560 


Asp Asp Thr Asn Arg Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu 
                565                 570                 575     


Gly Glu Asn Ala Ser Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln 
            580                 585                 590         


Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser 
        595                 600                 605             


Tyr Leu Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met 
    610                 615                 620                 


Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr 
625                 630                 635                 640 


Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile 
                645                 650                 655     


Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys 
            660                 665                 670         


Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr 
        675                 680                 685             


Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    690                 695                 700                 


<210>  25
<211>  704
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Original CSSK with modified alpha signal sequence

<400>  25

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu 
                85                  90                  95      


Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu Thr 
            100                 105                 110         


Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu 
        115                 120                 125             


Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn 
    130                 135                 140                 


Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys 
145                 150                 155                 160 


Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly 
                165                 170                 175     


Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser 
            180                 185                 190         


Ser Gly Ser Gly Pro Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp 
        195                 200                 205             


Leu Leu Asp Arg Pro Ser Val Asn Asn Ser Gln Leu Val Val Ser Val 
    210                 215                 220                 


Ala Gly Thr Val Glu Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe 
225                 230                 235                 240 


Glu Ile Asp Leu Thr Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln 
                245                 250                 255     


Gly Leu Ser Pro Lys Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met 
            260                 265                 270         


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


Leu Ile Ala Asn Val His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp 
    290                 295                 300                 


Phe Ala Ser Asp Ala Thr Ile Thr Asp Pro Asn Gly Lys Val Tyr Phe 
305                 310                 315                 320 


Ala Asp Lys Asp Gly Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu 
                325                 330                 335     


Phe Leu Leu Ser Gly His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro 
            340                 345                 350         


Ile Gln Asn Gln Ala Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe 
        355                 360                 365             


Thr Pro Leu Asn Pro Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr 
    370                 375                 380                 


Lys Leu Leu Lys Thr Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu 
385                 390                 395                 400 


Leu Leu Ala Gln Ala Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr 
                405                 410                 415     


Thr Ile Tyr Glu Arg Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile 
            420                 425                 430         


Phe Arg Thr Ile Leu Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys 
        435                 440                 445             


Asn Arg Glu Gln Ala Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu 
    450                 455                 460                 


Glu Ile Asn Asn Thr Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys 
465                 470                 475                 480 


Lys Gly Glu Lys Pro Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu 
                485                 490                 495     


Phe Thr Ile Lys Tyr Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser 
            500                 505                 510         


Glu Gln Leu Leu Thr Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu 
        515                 520                 525             


Tyr Asp Pro Arg Asp Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala 
    530                 535                 540                 


Phe Gly Ile Met Asp Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His 
545                 550                 555                 560 


Asp Asp Thr Asn Arg Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu 
                565                 570                 575     


Gly Glu Asn Ala Ser Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln 
            580                 585                 590         


Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser 
        595                 600                 605             


Tyr Leu Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met 
    610                 615                 620                 


Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr 
625                 630                 635                 640 


Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile 
                645                 650                 655     


Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys 
            660                 665                 670         


Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr 
        675                 680                 685             


Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    690                 695                 700                 


<210>  26
<211>  2115
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Original CSSK with modified alpha signal sequence

<400>  26
atgagatttc cttcaatttt tactgcagtt ttattcgcag catcctccgc attagctgct       60

ccagtcaaca ctacaacaga agatgaaacg gcacaaattc cggctgaagc tgtcatcggt      120

tactcagatt tagaagggga tttcgatgtt gctgttttgc cattttccaa cagcacaaat      180

aacgggttat tgtttataaa tactactatt gccagcattg ctgctaaaga agaaggggta      240

tctctcgaga aaagagtgca agctcaacaa attgtgccca tagctgagaa gtgttttgat      300

catgctgctg ggacttccta tttggtcgga gaaacgtggg agaagcccta ccaaggctgg      360

atgatggtag attgtacttg cctgggagaa ggcagcggac gcatcacttg cacttctaga      420

aatagatgca acgatcagga cacaaggaca tcctatagaa ttggagacac ctggagcaag      480

aaggataatc gaggaaacct gctccagtgc atctgcacag gcaacggccg aggagagtgg      540

aagtgtgaga ggcacacctc tgtgcagacc acatcgagcg gatctggccc cttcaccgat      600

gttcgtattg ctggacctga gtggctgcta gaccgtccat ctgtcaacaa cagccaatta      660

gttgttagcg ttgctggtac tgttgagggg acgaatcaag acattagtct taaatttttt      720

gaaatcgatc taacatcacg acctgctcat ggaggaaaga cagagcaagg cttaagtcca      780

aaatcaaaac catttgctac tgatagtggc gcgatgtcac ataaacttga gaaagctgac      840

ttactaaagg ctattcaaga acaattgatc gctaacgtcc acagtaacga cgactacttt      900

gaggtcattg attttgcaag cgatgcaacc attactgatc caaacggcaa ggtctacttt      960

gctgacaaag atggttcggt aaccttgccg acccaacctg tccaagaatt tttgctaagc     1020

ggacatgtgc gcgttagacc atataaagaa aaaccaatac aaaaccaagc gaaatctgtt     1080

gatgtggaat atactgtaca gtttactccc ttaaaccctg atgacgattt cagaccaggt     1140

ctcaaagata ctaagctatt gaaaacacta gctatcggtg acaccatcac atctcaagaa     1200

ttactagctc aagcacaaag cattttaaac aaaaaccacc caggctatac gatttatgaa     1260

cgtgactcct caatcgtcac tcatgacaat gacattttcc gtacgatttt accaatggat     1320

caagagttat cttaccgtgt taaaaatcgg gaacaagctt ataggatcaa taaaaaatct     1380

ggtctgaatg aagaaataaa caacactgac ctgatctctg agaaatatta cgtccttaaa     1440

aaaggggaaa agccgtatga tccctttgat cgcagtcact tgaaactgtt caccatcaaa     1500

tacgttgatg tcgataccaa cgaattgcta aaaagtgagc agctcttaac agctagcgaa     1560

cgtaacttag acttcagaga tttatacgat cctcgtgata aggctaaact actctacaac     1620

aatctcgatg cttttggtat tatggactat accttaactg gaaaagtaga ggataatcac     1680

gatgacacca accgtatcat aaccgtttat atgggcaagc gacccgaagg agagaatgct     1740

agctatcatt tagccggtgg cggacaagct caacaaattg tgcccatagc tgagaagtgt     1800

tttgatcatg ctgctgggac ttcctatttg gtcggagaaa cgtgggagaa gccctaccaa     1860

ggctggatga tggtagattg tacttgcctg ggagaaggca gcggacgcat cacttgcact     1920

tctagaaata gatgcaacga tcaggacaca aggacatcct atagaattgg agacacctgg     1980

agcaagaagg ataatcgagg aaacctgctc cagtgcatct gcacaggcaa cggccgagga     2040

gagtggaagt gtgagaggca cacctctgtg cagaccacat cgagcggatc tggccccttc     2100

accgatgttc gttag                                                      2115


<210>  27
<211>  704
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK modified N-terminal original C-terminal with modified alpha 
       signal sequence

<400>  27

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu 
                85                  90                  95      


Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu Thr 
            100                 105                 110         


Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu 
        115                 120                 125             


Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn 
    130                 135                 140                 


Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys 
145                 150                 155                 160 


Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly 
                165                 170                 175     


Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser 
            180                 185                 190         


Ser Gly Ser Gly Pro Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp 
        195                 200                 205             


Leu Leu Asp Arg Pro Ser Val Asn Asn Ser Gln Leu Val Val Ser Val 
    210                 215                 220                 


Ala Gly Thr Val Glu Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe 
225                 230                 235                 240 


Glu Ile Asp Leu Thr Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln 
                245                 250                 255     


Gly Leu Ser Pro Lys Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met 
            260                 265                 270         


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


Leu Ile Ala Asn Val His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp 
    290                 295                 300                 


Phe Ala Ser Asp Ala Thr Ile Thr Asp Pro Asn Gly Lys Val Tyr Phe 
305                 310                 315                 320 


Ala Asp Lys Asp Gly Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu 
                325                 330                 335     


Phe Leu Leu Ser Gly His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro 
            340                 345                 350         


Ile Gln Asn Gln Ala Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe 
        355                 360                 365             


Thr Pro Leu Asn Pro Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr 
    370                 375                 380                 


Lys Leu Leu Lys Thr Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu 
385                 390                 395                 400 


Leu Leu Ala Gln Ala Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr 
                405                 410                 415     


Thr Ile Tyr Glu Arg Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile 
            420                 425                 430         


Phe Arg Thr Ile Leu Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys 
        435                 440                 445             


Asn Arg Glu Gln Ala Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu 
    450                 455                 460                 


Glu Ile Asn Asn Thr Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys 
465                 470                 475                 480 


Lys Gly Glu Lys Pro Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu 
                485                 490                 495     


Phe Thr Ile Lys Tyr Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser 
            500                 505                 510         


Glu Gln Leu Leu Thr Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu 
        515                 520                 525             


Tyr Asp Pro Arg Asp Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala 
    530                 535                 540                 


Phe Gly Ile Met Asp Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His 
545                 550                 555                 560 


Asp Asp Thr Asn Arg Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu 
                565                 570                 575     


Gly Glu Asn Ala Ser Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln 
            580                 585                 590         


Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser 
        595                 600                 605             


Tyr Leu Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met 
    610                 615                 620                 


Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr 
625                 630                 635                 640 


Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile 
                645                 650                 655     


Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys 
            660                 665                 670         


Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr 
        675                 680                 685             


Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    690                 695                 700                 


<210>  28
<211>  2115
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CSSK original 5' modified 3' with modified alpha signal sequence

<400>  28
atgagatttc cttcaatttt tactgcagtt ttattcgcag catcctccgc attagctgct       60

ccagtcaaca ctacaacaga agatgaaacg gcacaaattc cggctgaagc tgtcatcggt      120

tactcagatt tagaagggga tttcgatgtt gctgttttgc cattttccaa cagcacaaat      180

aacgggttat tgtttataaa tactactatt gccagcattg ctgctaaaga agaaggggta      240

tctctcgaga aaagagttca agcccagcag attgttccaa tcgctgagaa gtgtttcgat      300

cacgctgctg gtacttcata cttggtcggt gaaacctggg aaaagccata ccagggatgg      360

atgatggttg actgcacctg tttaggtgaa ggttccggta gaatcacctg tacctccaga      420

aacagatgta acgaccagga caccagaacc tcttacagaa tcggtgatac ctggtccaag      480

aaggacaaca gaggtaacct gttgcagtgt atctgtaccg gtaacggtcg tggagaatgg      540

aagtgcgaga gacacacttc cgttcaaact acttcttccg gttccggtcc attcactgat      600

gttagaatcg ctggtccaga atggttgttg gacagaccat ccgttaacaa ctcccagttg      660

gttgtttctg ttgctggtac tgttgaggga actaaccagg acatctcctt gaagttcttc      720

gagatcgact tgacttctag accagctcat ggtggaaaga ctgagcaagg cttaagtcca      780

aaatcaaaac catttgctac tgatagtggc gcgatgtcac ataaacttga gaaagctgac      840

ttactaaagg ctattcaaga acaattgatc gctaacgtcc acagtaacga cgactacttt      900

gaggtcattg attttgcaag cgatgcaacc attactgatc caaacggcaa ggtctacttt      960

gctgacaaag atggttcggt aaccttgccg acccaacctg tccaagaatt tttgctaagc     1020

ggacatgtgc gcgttagacc atataaagaa aaaccaatac aaaaccaagc gaaatctgtt     1080

gatgtggaat atactgtaca gtttactccc ttaaaccctg atgacgattt cagaccaggt     1140

ctcaaagata ctaagctatt gaaaacacta gctatcggtg acaccatcac atctcaagaa     1200

ttactagctc aagcacaaag cattttaaac aaaaaccacc caggctatac gatttatgaa     1260

cgtgactcct caatcgtcac tcatgacaat gacattttcc gtacgatttt accaatggat     1320

caagagttat cttaccgtgt taaaaatcgg gaacaagctt ataggatcaa taaaaaatct     1380

ggtctgaatg aagaaataaa caacactgac ctgatctctg agaaatatta cgtccttaaa     1440

aaaggggaaa agccgtatga tccctttgat cgcagtcact tgaaactgtt caccatcaaa     1500

tacgttgatg tcgataccaa cgaattgcta aaaagtgagc agctcttaac agctagcgaa     1560

cgtaacttag acttcagaga tttatacgat cctcgtgata aggctaaact actctacaac     1620

aatctcgatg cttttggtat tatggactat accttaactg gaaaagtaga ggataatcac     1680

gatgacacca accgtatcat aaccgtttat atgggcaagc gacccgaagg agagaatgct     1740

agctatcatt tagccggtgg cggacaagct caacaaattg tgcccatagc tgagaagtgt     1800

tttgatcatg ctgctgggac ttcctatttg gtcggagaaa cgtgggagaa gccctaccaa     1860

ggctggatga tggtagattg tacttgcctg ggagaaggca gcggacgcat cacttgcact     1920

tctagaaata gatgcaacga tcaggacaca aggacatcct atagaattgg agacacctgg     1980

agcaagaagg ataatcgagg aaacctgctc cagtgcatct gcacaggcaa cggccgagga     2040

gagtggaagt gtgagaggca cacctctgtg cagaccacat cgagcggatc tggccccttc     2100

accgatgttc gttag                                                      2115


<210>  29
<211>  704
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CSSK original N-terminal modified C-terminal with modified alpha 
       signal sequence

<400>  29

Met Arg Phe Pro Ser Ile Phe Thr Ala Val Leu Phe Ala Ala Ser Ser 
1               5                   10                  15      


Ala Leu Ala Ala Pro Val Asn Thr Thr Thr Glu Asp Glu Thr Ala Gln 
            20                  25                  30          


Ile Pro Ala Glu Ala Val Ile Gly Tyr Ser Asp Leu Glu Gly Asp Phe 
        35                  40                  45              


Asp Val Ala Val Leu Pro Phe Ser Asn Ser Thr Asn Asn Gly Leu Leu 
    50                  55                  60                  


Phe Ile Asn Thr Thr Ile Ala Ser Ile Ala Ala Lys Glu Glu Gly Val 
65                  70                  75                  80  


Ser Leu Glu Lys Arg Val Gln Ala Gln Gln Ile Val Pro Ile Ala Glu 
                85                  90                  95      


Lys Cys Phe Asp His Ala Ala Gly Thr Ser Tyr Leu Val Gly Glu Thr 
            100                 105                 110         


Trp Glu Lys Pro Tyr Gln Gly Trp Met Met Val Asp Cys Thr Cys Leu 
        115                 120                 125             


Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr Ser Arg Asn Arg Cys Asn 
    130                 135                 140                 


Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile Gly Asp Thr Trp Ser Lys 
145                 150                 155                 160 


Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys Ile Cys Thr Gly Asn Gly 
                165                 170                 175     


Arg Gly Glu Trp Lys Cys Glu Arg His Thr Ser Val Gln Thr Thr Ser 
            180                 185                 190         


Ser Gly Ser Gly Pro Phe Thr Asp Val Arg Ile Ala Gly Pro Glu Trp 
        195                 200                 205             


Leu Leu Asp Arg Pro Ser Val Asn Asn Ser Gln Leu Val Val Ser Val 
    210                 215                 220                 


Ala Gly Thr Val Glu Gly Thr Asn Gln Asp Ile Ser Leu Lys Phe Phe 
225                 230                 235                 240 


Glu Ile Asp Leu Thr Ser Arg Pro Ala His Gly Gly Lys Thr Glu Gln 
                245                 250                 255     


Gly Leu Ser Pro Lys Ser Lys Pro Phe Ala Thr Asp Ser Gly Ala Met 
            260                 265                 270         


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


Leu Ile Ala Asn Val His Ser Asn Asp Asp Tyr Phe Glu Val Ile Asp 
    290                 295                 300                 


Phe Ala Ser Asp Ala Thr Ile Thr Asp Pro Asn Gly Lys Val Tyr Phe 
305                 310                 315                 320 


Ala Asp Lys Asp Gly Ser Val Thr Leu Pro Thr Gln Pro Val Gln Glu 
                325                 330                 335     


Phe Leu Leu Ser Gly His Val Arg Val Arg Pro Tyr Lys Glu Lys Pro 
            340                 345                 350         


Ile Gln Asn Gln Ala Lys Ser Val Asp Val Glu Tyr Thr Val Gln Phe 
        355                 360                 365             


Thr Pro Leu Asn Pro Asp Asp Asp Phe Arg Pro Gly Leu Lys Asp Thr 
    370                 375                 380                 


Lys Leu Leu Lys Thr Leu Ala Ile Gly Asp Thr Ile Thr Ser Gln Glu 
385                 390                 395                 400 


Leu Leu Ala Gln Ala Gln Ser Ile Leu Asn Lys Asn His Pro Gly Tyr 
                405                 410                 415     


Thr Ile Tyr Glu Arg Asp Ser Ser Ile Val Thr His Asp Asn Asp Ile 
            420                 425                 430         


Phe Arg Thr Ile Leu Pro Met Asp Gln Glu Leu Ser Tyr Arg Val Lys 
        435                 440                 445             


Asn Arg Glu Gln Ala Tyr Arg Ile Asn Lys Lys Ser Gly Leu Asn Glu 
    450                 455                 460                 


Glu Ile Asn Asn Thr Asp Leu Ile Ser Glu Lys Tyr Tyr Val Leu Lys 
465                 470                 475                 480 


Lys Gly Glu Lys Pro Tyr Asp Pro Phe Asp Arg Ser His Leu Lys Leu 
                485                 490                 495     


Phe Thr Ile Lys Tyr Val Asp Val Asp Thr Asn Glu Leu Leu Lys Ser 
            500                 505                 510         


Glu Gln Leu Leu Thr Ala Ser Glu Arg Asn Leu Asp Phe Arg Asp Leu 
        515                 520                 525             


Tyr Asp Pro Arg Asp Lys Ala Lys Leu Leu Tyr Asn Asn Leu Asp Ala 
    530                 535                 540                 


Phe Gly Ile Met Asp Tyr Thr Leu Thr Gly Lys Val Glu Asp Asn His 
545                 550                 555                 560 


Asp Asp Thr Asn Arg Ile Ile Thr Val Tyr Met Gly Lys Arg Pro Glu 
                565                 570                 575     


Gly Glu Asn Ala Ser Tyr His Leu Ala Gly Gly Gly Gln Ala Gln Gln 
            580                 585                 590         


Ile Val Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly Thr Ser 
        595                 600                 605             


Tyr Leu Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp Met Met 
    610                 615                 620                 


Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr Cys Thr 
625                 630                 635                 640 


Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr Arg Ile 
                645                 650                 655     


Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu Gln Cys 
            660                 665                 670         


Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg His Thr 
        675                 680                 685             


Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp Val Arg 
    690                 695                 700                 


<210>  30
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  5' AOX1 forward primer sequence

<400>  30
gactggttcc aattgacaag c                                                 21


<210>  31
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3' AOX1 reverse primer

<400>  31
gcaaatggca ttctgacatc c                                                 21


<210>  32
<211>  33
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Forward Primer

<400>  32
gacagcctcg agaaaagagt gcaagctcaa caa                                    33


<210>  33
<211>  33
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Primer sequence

<400>  33
gacagcctcg agaaaagagt gcaagctcaa caa                                    33


