                         SEQUENCE LISTING

<110>  OTTAWA HOSPITAL RESEARCH INSTITUTE
       UNITED THERAPEUTICS CORPORATION
 
<120>  GENETICALLY-ENGINEERED MESENCHYMAL STEM CELLS OVERPRESSING AOAH 
       AND USES THEREOF

<130>  G17018-00007

<150>  US 62/752,000
<151>  2018-10-29

<160>  8     

<170>  PatentIn version 3.5

<210>  1
<211>  1734
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (7)..(1734)

<400>  1
gccacc atg cag tcc ccc tgg aag att ctg acc gtg gca ccc ctg ttt          48
       Met Gln Ser Pro Trp Lys Ile Leu Thr Val Ala Pro Leu Phe            
       1               5                   10                             

ctg ctg ctg tcc ctg cag tcc tcc gca agc ccc gca aat gat gat cag         96
Leu Leu Leu Ser Leu Gln Ser Ser Ala Ser Pro Ala Asn Asp Asp Gln           
15                  20                  25                  30            

tcc agg cct tcc ctg tct aac gga cac acc tgc gtg gga tgc gtg ctg        144
Ser Arg Pro Ser Leu Ser Asn Gly His Thr Cys Val Gly Cys Val Leu           
                35                  40                  45                

gtg gtg tct gtg atc gag cag ctg gcc cag gtg cac aat tct aca gtg        192
Val Val Ser Val Ile Glu Gln Leu Ala Gln Val His Asn Ser Thr Val           
            50                  55                  60                    

cag gcc agc atg gag cgc ctg tgc tcc tac ctg cca gag aag ctg ttt        240
Gln Ala Ser Met Glu Arg Leu Cys Ser Tyr Leu Pro Glu Lys Leu Phe           
        65                  70                  75                        

ctg aag acc aca tgt tac ctg gtc atc gat aag ttc ggc agc gac atc        288
Leu Lys Thr Thr Cys Tyr Leu Val Ile Asp Lys Phe Gly Ser Asp Ile           
    80                  85                  90                            

atc aag ctg ctg tcc gcc gac atg aac gcc gac gtg gtg tgc cac acc        336
Ile Lys Leu Leu Ser Ala Asp Met Asn Ala Asp Val Val Cys His Thr           
95                  100                 105                 110           

ctg gag ttt tgt aag cag aat aca ggc cag cct ctg tgc cac ctg tac        384
Leu Glu Phe Cys Lys Gln Asn Thr Gly Gln Pro Leu Cys His Leu Tyr           
                115                 120                 125               

ccc ctg cct aag gag aca tgg aag ttc aca ctg cag aag gcc agg cag        432
Pro Leu Pro Lys Glu Thr Trp Lys Phe Thr Leu Gln Lys Ala Arg Gln           
            130                 135                 140                   

atc gtg aag aag tct cca atc ctg aag tat agc cgc tcc ggc tct gat        480
Ile Val Lys Lys Ser Pro Ile Leu Lys Tyr Ser Arg Ser Gly Ser Asp           
        145                 150                 155                       

atc tgc agc ctg ccc gtg ctg gcc aag att tgc cag aag atc aag ctg        528
Ile Cys Ser Leu Pro Val Leu Ala Lys Ile Cys Gln Lys Ile Lys Leu           
    160                 165                 170                           

gcc atg gag cag agc gtg ccc ttt aag gac gtg gat agc gac aag tac        576
Ala Met Glu Gln Ser Val Pro Phe Lys Asp Val Asp Ser Asp Lys Tyr           
175                 180                 185                 190           

tcc gtg ttc cct acc ctg agg gga tat cac tgg agg gga agg gac tgt        624
Ser Val Phe Pro Thr Leu Arg Gly Tyr His Trp Arg Gly Arg Asp Cys           
                195                 200                 205               

aac gat tct gac gag agc gtg tac cct ggc aga cgg ccc aac aat tgg        672
Asn Asp Ser Asp Glu Ser Val Tyr Pro Gly Arg Arg Pro Asn Asn Trp           
            210                 215                 220                   

gat gtg cac cag gac agc aac tgc aat ggc atc tgg gga gtg gat cca        720
Asp Val His Gln Asp Ser Asn Cys Asn Gly Ile Trp Gly Val Asp Pro           
        225                 230                 235                       

aag gac gga gtg cct tat gag aag aag ttt tgt gag ggc tcc cag cct        768
Lys Asp Gly Val Pro Tyr Glu Lys Lys Phe Cys Glu Gly Ser Gln Pro           
    240                 245                 250                           

aga ggc atc atc ctg ctg ggc gac tcc gcc gga gca cac ttt cac atc        816
Arg Gly Ile Ile Leu Leu Gly Asp Ser Ala Gly Ala His Phe His Ile           
255                 260                 265                 270           

tct cca gag tgg atc acc gcc tcc cag atg tct ctg aac agc ttc atc        864
Ser Pro Glu Trp Ile Thr Ala Ser Gln Met Ser Leu Asn Ser Phe Ile           
                275                 280                 285               

aat ctg cca acc gcc ctg aca aat gag ctg gat tgg cca cag ctg agc        912
Asn Leu Pro Thr Ala Leu Thr Asn Glu Leu Asp Trp Pro Gln Leu Ser           
            290                 295                 300                   

gga gca acc ggc ttt ctg gac tcc aca gtg ggc atc aag gag aag tct        960
Gly Ala Thr Gly Phe Leu Asp Ser Thr Val Gly Ile Lys Glu Lys Ser           
        305                 310                 315                       

atc tac ctg cgg ctg tgg aag aga aac cac tgc aat cac cgg gat tat       1008
Ile Tyr Leu Arg Leu Trp Lys Arg Asn His Cys Asn His Arg Asp Tyr           
    320                 325                 330                           

cag aac atc tct agg aat ggc gcc agc tcc cgc aac ctg aag aag ttc       1056
Gln Asn Ile Ser Arg Asn Gly Ala Ser Ser Arg Asn Leu Lys Lys Phe           
335                 340                 345                 350           

atc gag agc ctg tcc aga aat aag gtg ctg gac tac cca gcc atc gtg       1104
Ile Glu Ser Leu Ser Arg Asn Lys Val Leu Asp Tyr Pro Ala Ile Val           
                355                 360                 365               

atc tat gcc atg atc ggc aac gac gtg tgc tcc ggc aag tct gac cca       1152
Ile Tyr Ala Met Ile Gly Asn Asp Val Cys Ser Gly Lys Ser Asp Pro           
            370                 375                 380                   

gtg ccc gcc atg acc aca ccc gag aag ctg tac agc aat gtg atg cag       1200
Val Pro Ala Met Thr Thr Pro Glu Lys Leu Tyr Ser Asn Val Met Gln           
        385                 390                 395                       

acc ctg aag cac ctg aac tcc cac ctg cct aat ggc tct cac gtg atc       1248
Thr Leu Lys His Leu Asn Ser His Leu Pro Asn Gly Ser His Val Ile           
    400                 405                 410                           

ctg tac ggc ctg cca gat ggc acc ttt ctg tgg gac aac ctg cac aat       1296
Leu Tyr Gly Leu Pro Asp Gly Thr Phe Leu Trp Asp Asn Leu His Asn           
415                 420                 425                 430           

agg tat cac ccc ctg ggc cag ctg aac aag gat atg aca tac gcc cag       1344
Arg Tyr His Pro Leu Gly Gln Leu Asn Lys Asp Met Thr Tyr Ala Gln           
                435                 440                 445               

ctg tat agc ttc ctg aat tgc ctg cag gtg tcc cct tgt cac ggc tgg       1392
Leu Tyr Ser Phe Leu Asn Cys Leu Gln Val Ser Pro Cys His Gly Trp           
            450                 455                 460                   

atg tct agc aac aag aca ctg cgg acc ctg aca tct gag aga gcc gag       1440
Met Ser Ser Asn Lys Thr Leu Arg Thr Leu Thr Ser Glu Arg Ala Glu           
        465                 470                 475                       

cag ctg agc aat acc ctg aag aag atc gcc gcc tcc gag aag ttc aca       1488
Gln Leu Ser Asn Thr Leu Lys Lys Ile Ala Ala Ser Glu Lys Phe Thr           
    480                 485                 490                           

aac ttt aat ctg ttc tac atg gac ttc gcc ttt cac gag atc atc cag       1536
Asn Phe Asn Leu Phe Tyr Met Asp Phe Ala Phe His Glu Ile Ile Gln           
495                 500                 505                 510           

gag tgg cag aag aga gga gga cag cca tgg cag ctg atc gag cca gtg       1584
Glu Trp Gln Lys Arg Gly Gly Gln Pro Trp Gln Leu Ile Glu Pro Val           
                515                 520                 525               

gat ggc ttt cac cct aac gag gtg gcc ctg ctg ctg ctg gcc gac cac       1632
Asp Gly Phe His Pro Asn Glu Val Ala Leu Leu Leu Leu Ala Asp His           
            530                 535                 540                   

ttc tgg aag aag gtg cag ctg cag tgg ccc cag atc ctg ggg aaa gaa       1680
Phe Trp Lys Lys Val Gln Leu Gln Trp Pro Gln Ile Leu Gly Lys Glu           
        545                 550                 555                       

aac cca ttc aac cca cag att aag cag gtg ttc ggg gac cag ggc ggg       1728
Asn Pro Phe Asn Pro Gln Ile Lys Gln Val Phe Gly Asp Gln Gly Gly           
    560                 565                 570                           

cac tag                                                               1734
His                                                                       
575                                                                       


<210>  2
<211>  575
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Gln Ser Pro Trp Lys Ile Leu Thr Val Ala Pro Leu Phe Leu Leu 
1               5                   10                  15      


Leu Ser Leu Gln Ser Ser Ala Ser Pro Ala Asn Asp Asp Gln Ser Arg 
            20                  25                  30          


Pro Ser Leu Ser Asn Gly His Thr Cys Val Gly Cys Val Leu Val Val 
        35                  40                  45              


Ser Val Ile Glu Gln Leu Ala Gln Val His Asn Ser Thr Val Gln Ala 
    50                  55                  60                  


Ser Met Glu Arg Leu Cys Ser Tyr Leu Pro Glu Lys Leu Phe Leu Lys 
65                  70                  75                  80  


Thr Thr Cys Tyr Leu Val Ile Asp Lys Phe Gly Ser Asp Ile Ile Lys 
                85                  90                  95      


Leu Leu Ser Ala Asp Met Asn Ala Asp Val Val Cys His Thr Leu Glu 
            100                 105                 110         


Phe Cys Lys Gln Asn Thr Gly Gln Pro Leu Cys His Leu Tyr Pro Leu 
        115                 120                 125             


Pro Lys Glu Thr Trp Lys Phe Thr Leu Gln Lys Ala Arg Gln Ile Val 
    130                 135                 140                 


Lys Lys Ser Pro Ile Leu Lys Tyr Ser Arg Ser Gly Ser Asp Ile Cys 
145                 150                 155                 160 


Ser Leu Pro Val Leu Ala Lys Ile Cys Gln Lys Ile Lys Leu Ala Met 
                165                 170                 175     


Glu Gln Ser Val Pro Phe Lys Asp Val Asp Ser Asp Lys Tyr Ser Val 
            180                 185                 190         


Phe Pro Thr Leu Arg Gly Tyr His Trp Arg Gly Arg Asp Cys Asn Asp 
        195                 200                 205             


Ser Asp Glu Ser Val Tyr Pro Gly Arg Arg Pro Asn Asn Trp Asp Val 
    210                 215                 220                 


His Gln Asp Ser Asn Cys Asn Gly Ile Trp Gly Val Asp Pro Lys Asp 
225                 230                 235                 240 


Gly Val Pro Tyr Glu Lys Lys Phe Cys Glu Gly Ser Gln Pro Arg Gly 
                245                 250                 255     


Ile Ile Leu Leu Gly Asp Ser Ala Gly Ala His Phe His Ile Ser Pro 
            260                 265                 270         


Glu Trp Ile Thr Ala Ser Gln Met Ser Leu Asn Ser Phe Ile Asn Leu 
        275                 280                 285             


Pro Thr Ala Leu Thr Asn Glu Leu Asp Trp Pro Gln Leu Ser Gly Ala 
    290                 295                 300                 


Thr Gly Phe Leu Asp Ser Thr Val Gly Ile Lys Glu Lys Ser Ile Tyr 
305                 310                 315                 320 


Leu Arg Leu Trp Lys Arg Asn His Cys Asn His Arg Asp Tyr Gln Asn 
                325                 330                 335     


Ile Ser Arg Asn Gly Ala Ser Ser Arg Asn Leu Lys Lys Phe Ile Glu 
            340                 345                 350         


Ser Leu Ser Arg Asn Lys Val Leu Asp Tyr Pro Ala Ile Val Ile Tyr 
        355                 360                 365             


Ala Met Ile Gly Asn Asp Val Cys Ser Gly Lys Ser Asp Pro Val Pro 
    370                 375                 380                 


Ala Met Thr Thr Pro Glu Lys Leu Tyr Ser Asn Val Met Gln Thr Leu 
385                 390                 395                 400 


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


Gly Leu Pro Asp Gly Thr Phe Leu Trp Asp Asn Leu His Asn Arg Tyr 
            420                 425                 430         


His Pro Leu Gly Gln Leu Asn Lys Asp Met Thr Tyr Ala Gln Leu Tyr 
        435                 440                 445             


Ser Phe Leu Asn Cys Leu Gln Val Ser Pro Cys His Gly Trp Met Ser 
    450                 455                 460                 


Ser Asn Lys Thr Leu Arg Thr Leu Thr Ser Glu Arg Ala Glu Gln Leu 
465                 470                 475                 480 


Ser Asn Thr Leu Lys Lys Ile Ala Ala Ser Glu Lys Phe Thr Asn Phe 
                485                 490                 495     


Asn Leu Phe Tyr Met Asp Phe Ala Phe His Glu Ile Ile Gln Glu Trp 
            500                 505                 510         


Gln Lys Arg Gly Gly Gln Pro Trp Gln Leu Ile Glu Pro Val Asp Gly 
        515                 520                 525             


Phe His Pro Asn Glu Val Ala Leu Leu Leu Leu Ala Asp His Phe Trp 
    530                 535                 540                 


Lys Lys Val Gln Leu Gln Trp Pro Gln Ile Leu Gly Lys Glu Asn Pro 
545                 550                 555                 560 


Phe Asn Pro Gln Ile Lys Gln Val Phe Gly Asp Gln Gly Gly His 
                565                 570                 575 


<210>  3
<211>  1503
<212>  DNA
<213>  Homo sapiens


<220>
<221>  CDS
<222>  (7)..(1503)

<400>  3
gccacc atg aca gtt ttc ctt tcc ttt gct ttc ctc gct gcc att ctg          48
       Met Thr Val Phe Leu Ser Phe Ala Phe Leu Ala Ala Ile Leu            
       1               5                   10                             

act cac ata ggg tgc agc aat cag cgc cga agt cca gaa aac agt ggg         96
Thr His Ile Gly Cys Ser Asn Gln Arg Arg Ser Pro Glu Asn Ser Gly           
15                  20                  25                  30            

aga aga tat aac cgg att caa cat ggg caa tgt gcc tac act ttc att        144
Arg Arg Tyr Asn Arg Ile Gln His Gly Gln Cys Ala Tyr Thr Phe Ile           
                35                  40                  45                

ctt cca gaa cac gat ggc aac tgt cgt gag agt acg aca gac cag tac        192
Leu Pro Glu His Asp Gly Asn Cys Arg Glu Ser Thr Thr Asp Gln Tyr           
            50                  55                  60                    

aac aca aac gct ctg cag aga gat gct cca cac gtg gaa ccg gat ttc        240
Asn Thr Asn Ala Leu Gln Arg Asp Ala Pro His Val Glu Pro Asp Phe           
        65                  70                  75                        

tct tcc cag aaa ctt caa cat ctg gaa cat gtg atg gaa aat tat act        288
Ser Ser Gln Lys Leu Gln His Leu Glu His Val Met Glu Asn Tyr Thr           
    80                  85                  90                            

cag tgg ctg caa aaa ctt gag aat tac att gtg gaa aac atg aag tcg        336
Gln Trp Leu Gln Lys Leu Glu Asn Tyr Ile Val Glu Asn Met Lys Ser           
95                  100                 105                 110           

gag atg gcc cag ata cag cag aat gca gtt cag aac cac acg gct acc        384
Glu Met Ala Gln Ile Gln Gln Asn Ala Val Gln Asn His Thr Ala Thr           
                115                 120                 125               

atg ctg gag ata gga acc agc ctc ctc tct cag act gca gag cag acc        432
Met Leu Glu Ile Gly Thr Ser Leu Leu Ser Gln Thr Ala Glu Gln Thr           
            130                 135                 140                   

aga aag ctg aca gat gtt gag acc cag gta cta aat caa act tct cga        480
Arg Lys Leu Thr Asp Val Glu Thr Gln Val Leu Asn Gln Thr Ser Arg           
        145                 150                 155                       

ctt gag ata cag ctg ctg gag aat tca tta tcc acc tac aag cta gag        528
Leu Glu Ile Gln Leu Leu Glu Asn Ser Leu Ser Thr Tyr Lys Leu Glu           
    160                 165                 170                           

aag caa ctt ctt caa cag aca aat gaa atc ttg aag atc cat gaa aaa        576
Lys Gln Leu Leu Gln Gln Thr Asn Glu Ile Leu Lys Ile His Glu Lys           
175                 180                 185                 190           

aac agt tta tta gaa cat aaa atc tta gaa atg gaa gga aaa cac aag        624
Asn Ser Leu Leu Glu His Lys Ile Leu Glu Met Glu Gly Lys His Lys           
                195                 200                 205               

gaa gag ttg gac acc tta aag gaa gag aaa gag aac ctt caa ggc ttg        672
Glu Glu Leu Asp Thr Leu Lys Glu Glu Lys Glu Asn Leu Gln Gly Leu           
            210                 215                 220                   

gtt act cgt caa aca tat ata atc cag gag ctg gaa aag caa tta aac        720
Val Thr Arg Gln Thr Tyr Ile Ile Gln Glu Leu Glu Lys Gln Leu Asn           
        225                 230                 235                       

aga gct acc acc aac aac agt gtc ctt cag aag cag caa ctg gag ctg        768
Arg Ala Thr Thr Asn Asn Ser Val Leu Gln Lys Gln Gln Leu Glu Leu           
    240                 245                 250                           

atg gac aca gtc cac aac ctt gtc aat ctt tgc act aaa gaa ggt gtt        816
Met Asp Thr Val His Asn Leu Val Asn Leu Cys Thr Lys Glu Gly Val           
255                 260                 265                 270           

tta cta aag gga gga aaa aga gag gaa gag aaa cca ttt aga gac tgt        864
Leu Leu Lys Gly Gly Lys Arg Glu Glu Glu Lys Pro Phe Arg Asp Cys           
                275                 280                 285               

gca gat gta tat caa gct ggt ttt aat aaa agt gga atc tac act att        912
Ala Asp Val Tyr Gln Ala Gly Phe Asn Lys Ser Gly Ile Tyr Thr Ile           
            290                 295                 300                   

tat att aat aat atg cca gaa ccc aaa aag gtg ttt tgc aat atg gat        960
Tyr Ile Asn Asn Met Pro Glu Pro Lys Lys Val Phe Cys Asn Met Asp           
        305                 310                 315                       

gtc aat ggg gga ggt tgg act gta ata caa cat cgt gaa gat gga agt       1008
Val Asn Gly Gly Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser           
    320                 325                 330                           

cta gat ttc caa aga ggc tgg aag gaa tat aaa atg ggt ttt gga aat       1056
Leu Asp Phe Gln Arg Gly Trp Lys Glu Tyr Lys Met Gly Phe Gly Asn           
335                 340                 345                 350           

ccc tcc ggt gaa tat tgg ctg ggg aat gag ttt att ttt gcc att acc       1104
Pro Ser Gly Glu Tyr Trp Leu Gly Asn Glu Phe Ile Phe Ala Ile Thr           
                355                 360                 365               

agt cag agg cag tac atg cta aga att gag tta atg gac tgg gaa ggg       1152
Ser Gln Arg Gln Tyr Met Leu Arg Ile Glu Leu Met Asp Trp Glu Gly           
            370                 375                 380                   

aac cga gcc tat tca cag tat gac aga ttc cac ata gga aat gaa aag       1200
Asn Arg Ala Tyr Ser Gln Tyr Asp Arg Phe His Ile Gly Asn Glu Lys           
        385                 390                 395                       

caa aac tat agg ttg tat tta aaa ggt cac act ggg aca gca gga aaa       1248
Gln Asn Tyr Arg Leu Tyr Leu Lys Gly His Thr Gly Thr Ala Gly Lys           
    400                 405                 410                           

cag agc agc ctg atc tta cac ggt gct gat ttc agc act aaa gat gct       1296
Gln Ser Ser Leu Ile Leu His Gly Ala Asp Phe Ser Thr Lys Asp Ala           
415                 420                 425                 430           

gat aat gac aac tgt atg tgc aaa tgt gcc ctc atg tta aca gga gga       1344
Asp Asn Asp Asn Cys Met Cys Lys Cys Ala Leu Met Leu Thr Gly Gly           
                435                 440                 445               

tgg tgg ttt gat gct tgt ggc ccc tcc aat cta aat gga atg ttc tat       1392
Trp Trp Phe Asp Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Phe Tyr           
            450                 455                 460                   

act gcg gga caa aac cat gga aaa ctg aat ggg ata aag tgg cac tac       1440
Thr Ala Gly Gln Asn His Gly Lys Leu Asn Gly Ile Lys Trp His Tyr           
        465                 470                 475                       

ttc aaa ggg ccc agt tac tcc tta cgt tcc aca act atg atg att cga       1488
Phe Lys Gly Pro Ser Tyr Ser Leu Arg Ser Thr Thr Met Met Ile Arg           
    480                 485                 490                           

cct tta gat ttt tag                                                   1503
Pro Leu Asp Phe                                                           
495                                                                       


<210>  4
<211>  498
<212>  PRT
<213>  Homo sapiens

<400>  4

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


Ile Gly Cys Ser Asn Gln Arg Arg Ser Pro Glu Asn Ser Gly Arg Arg 
            20                  25                  30          


Tyr Asn Arg Ile Gln His Gly Gln Cys Ala Tyr Thr Phe Ile Leu Pro 
        35                  40                  45              


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


Asn Ala Leu Gln Arg Asp Ala Pro His Val Glu Pro Asp Phe Ser Ser 
65                  70                  75                  80  


Gln Lys Leu Gln His Leu Glu His Val Met Glu Asn Tyr Thr Gln Trp 
                85                  90                  95      


Leu Gln Lys Leu Glu Asn Tyr Ile Val Glu Asn Met Lys Ser Glu Met 
            100                 105                 110         


Ala Gln Ile Gln Gln Asn Ala Val Gln Asn His Thr Ala Thr Met Leu 
        115                 120                 125             


Glu Ile Gly Thr Ser Leu Leu Ser Gln Thr Ala Glu Gln Thr Arg Lys 
    130                 135                 140                 


Leu Thr Asp Val Glu Thr Gln Val Leu Asn Gln Thr Ser Arg Leu Glu 
145                 150                 155                 160 


Ile Gln Leu Leu Glu Asn Ser Leu Ser Thr Tyr Lys Leu Glu Lys Gln 
                165                 170                 175     


Leu Leu Gln Gln Thr Asn Glu Ile Leu Lys Ile His Glu Lys Asn Ser 
            180                 185                 190         


Leu Leu Glu His Lys Ile Leu Glu Met Glu Gly Lys His Lys Glu Glu 
        195                 200                 205             


Leu Asp Thr Leu Lys Glu Glu Lys Glu Asn Leu Gln Gly Leu Val Thr 
    210                 215                 220                 


Arg Gln Thr Tyr Ile Ile Gln Glu Leu Glu Lys Gln Leu Asn Arg Ala 
225                 230                 235                 240 


Thr Thr Asn Asn Ser Val Leu Gln Lys Gln Gln Leu Glu Leu Met Asp 
                245                 250                 255     


Thr Val His Asn Leu Val Asn Leu Cys Thr Lys Glu Gly Val Leu Leu 
            260                 265                 270         


Lys Gly Gly Lys Arg Glu Glu Glu Lys Pro Phe Arg Asp Cys Ala Asp 
        275                 280                 285             


Val Tyr Gln Ala Gly Phe Asn Lys Ser Gly Ile Tyr Thr Ile Tyr Ile 
    290                 295                 300                 


Asn Asn Met Pro Glu Pro Lys Lys Val Phe Cys Asn Met Asp Val Asn 
305                 310                 315                 320 


Gly Gly Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser Leu Asp 
                325                 330                 335     


Phe Gln Arg Gly Trp Lys Glu Tyr Lys Met Gly Phe Gly Asn Pro Ser 
            340                 345                 350         


Gly Glu Tyr Trp Leu Gly Asn Glu Phe Ile Phe Ala Ile Thr Ser Gln 
        355                 360                 365             


Arg Gln Tyr Met Leu Arg Ile Glu Leu Met Asp Trp Glu Gly Asn Arg 
    370                 375                 380                 


Ala Tyr Ser Gln Tyr Asp Arg Phe His Ile Gly Asn Glu Lys Gln Asn 
385                 390                 395                 400 


Tyr Arg Leu Tyr Leu Lys Gly His Thr Gly Thr Ala Gly Lys Gln Ser 
                405                 410                 415     


Ser Leu Ile Leu His Gly Ala Asp Phe Ser Thr Lys Asp Ala Asp Asn 
            420                 425                 430         


Asp Asn Cys Met Cys Lys Cys Ala Leu Met Leu Thr Gly Gly Trp Trp 
        435                 440                 445             


Phe Asp Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Phe Tyr Thr Ala 
    450                 455                 460                 


Gly Gln Asn His Gly Lys Leu Asn Gly Ile Lys Trp His Tyr Phe Lys 
465                 470                 475                 480 


Gly Pro Ser Tyr Ser Leu Arg Ser Thr Thr Met Met Ile Arg Pro Leu 
                485                 490                 495     


Asp Phe 
        


<210>  5
<211>  575
<212>  PRT
<213>  Homo sapiens


<220>
<221>  SIGNAL
<222>  (1)..(23)

<220>
<221>  PROPEP
<222>  (24)..(34)

<400>  5

Met Gln Ser Pro Trp Lys Ile Leu Thr Val Ala Pro Leu Phe Leu Leu 
1               5                   10                  15      


Leu Ser Leu Gln Ser Ser Ala Ser Pro Ala Asn Asp Asp Gln Ser Arg 
            20                  25                  30          


Pro Ser Leu Ser Asn Gly His Thr Cys Val Gly Cys Val Leu Val Val 
        35                  40                  45              


Ser Val Ile Glu Gln Leu Ala Gln Val His Asn Ser Thr Val Gln Ala 
    50                  55                  60                  


Ser Met Glu Arg Leu Cys Ser Tyr Leu Pro Glu Lys Leu Phe Leu Lys 
65                  70                  75                  80  


Thr Thr Cys Tyr Leu Val Ile Asp Lys Phe Gly Ser Asp Ile Ile Lys 
                85                  90                  95      


Leu Leu Ser Ala Asp Met Asn Ala Asp Val Val Cys His Thr Leu Glu 
            100                 105                 110         


Phe Cys Lys Gln Asn Thr Gly Gln Pro Leu Cys His Leu Tyr Pro Leu 
        115                 120                 125             


Pro Lys Glu Thr Trp Lys Phe Thr Leu Gln Lys Ala Arg Gln Ile Val 
    130                 135                 140                 


Lys Lys Ser Pro Ile Leu Lys Tyr Ser Arg Ser Gly Ser Asp Ile Cys 
145                 150                 155                 160 


Ser Leu Pro Val Leu Ala Lys Ile Cys Gln Lys Ile Lys Leu Ala Met 
                165                 170                 175     


Glu Gln Ser Val Pro Phe Lys Asp Val Asp Ser Asp Lys Tyr Ser Val 
            180                 185                 190         


Phe Pro Thr Leu Arg Gly Tyr His Trp Arg Gly Arg Asp Cys Asn Asp 
        195                 200                 205             


Ser Asp Glu Ser Val Tyr Pro Gly Arg Arg Pro Asn Asn Trp Asp Val 
    210                 215                 220                 


His Gln Asp Ser Asn Cys Asn Gly Ile Trp Gly Val Asp Pro Lys Asp 
225                 230                 235                 240 


Gly Val Pro Tyr Glu Lys Lys Phe Cys Glu Gly Ser Gln Pro Arg Gly 
                245                 250                 255     


Ile Ile Leu Leu Gly Asp Ser Ala Gly Ala His Phe His Ile Ser Pro 
            260                 265                 270         


Glu Trp Ile Thr Ala Ser Gln Met Ser Leu Asn Ser Phe Ile Asn Leu 
        275                 280                 285             


Pro Thr Ala Leu Thr Asn Glu Leu Asp Trp Pro Gln Leu Ser Gly Ala 
    290                 295                 300                 


Thr Gly Phe Leu Asp Ser Thr Val Gly Ile Lys Glu Lys Ser Ile Tyr 
305                 310                 315                 320 


Leu Arg Leu Trp Lys Arg Asn His Cys Asn His Arg Asp Tyr Gln Asn 
                325                 330                 335     


Ile Ser Arg Asn Gly Ala Ser Ser Arg Asn Leu Lys Lys Phe Ile Glu 
            340                 345                 350         


Ser Leu Ser Arg Asn Lys Val Leu Asp Tyr Pro Ala Ile Val Ile Tyr 
        355                 360                 365             


Ala Met Ile Gly Asn Asp Val Cys Ser Gly Lys Ser Asp Pro Val Pro 
    370                 375                 380                 


Ala Met Thr Thr Pro Glu Lys Leu Tyr Ser Asn Val Met Gln Thr Leu 
385                 390                 395                 400 


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


Gly Leu Pro Asp Gly Thr Phe Leu Trp Asp Asn Leu His Asn Arg Tyr 
            420                 425                 430         


His Pro Leu Gly Gln Leu Asn Lys Asp Met Thr Tyr Ala Gln Leu Tyr 
        435                 440                 445             


Ser Phe Leu Asn Cys Leu Gln Val Ser Pro Cys His Gly Trp Met Ser 
    450                 455                 460                 


Ser Asn Lys Thr Leu Arg Thr Leu Thr Ser Glu Arg Ala Glu Gln Leu 
465                 470                 475                 480 


Ser Asn Thr Leu Lys Lys Ile Ala Ala Ser Glu Lys Phe Thr Asn Phe 
                485                 490                 495     


Asn Leu Phe Tyr Met Asp Phe Ala Phe His Glu Ile Ile Gln Glu Trp 
            500                 505                 510         


Gln Lys Arg Gly Gly Gln Pro Trp Gln Leu Ile Glu Pro Val Asp Gly 
        515                 520                 525             


Phe His Pro Asn Glu Val Ala Leu Leu Leu Leu Ala Asp His Phe Trp 
    530                 535                 540                 


Lys Lys Val Gln Leu Gln Trp Pro Gln Ile Leu Gly Lys Glu Asn Pro 
545                 550                 555                 560 


Phe Asn Pro Gln Ile Lys Gln Val Phe Gly Asp Gln Gly Gly His 
                565                 570                 575 


<210>  6
<211>  2440
<212>  DNA
<213>  Homo sapiens

<400>  6
aacagatcag ttccggcaag cctcgaggct cacggggttt atgcacacta acttcactga       60

gccagggagc acggaagttg tgccactgtg caacttgggt tttctttatc ctgcagtctt      120

tacctcagca gaaccgcaca ccacagactc cctccagctc tttgtgtgtg gctctctcag      180

ggtccaacaa gagcaagctg tgggtctgtg agtgtttatg tgtgctttta ttcacttcac      240

acttattgaa aagtgtgtat gtgagagggt ggggtgtgtg tgtcaaagag agtgaggaag      300

agaaggagag agagatcaat tgattctgca gcctcagctc cagcatccct cagttgggag      360

cttccaaagc cgggtgatca cttggggtgc atagctcgga gatgcagtcc ccctggaaaa      420

tccttacggt ggcgcctcta ttcttgctcc tgtctcttca gtcctcggcc tctccagcca      480

acgatgacca gtccaggccc agcctctcga atgggcacac ctgtgtaggg tgtgtgctgg      540

tggtgtctgt aatagaacag cttgctcaag ttcacaactc gacggtccag gcctcgatgg      600

agagactgtg cagctacctg cctgaaaaac tgttcttgaa aaccacctgc tatttagtca      660

ttgacaagtt tggatcagac atcataaaac tgcttagcgc agatatgaat gctgatgtgg      720

tatgtcacac tctggagttt tgtaaacaga acactggcca accattgtgt catctctacc      780

ctcttcccaa ggagacatgg aaatttacac tacagaaggc aagacaaatt gtcaagaagt      840

ccccgattct gaaatattct agaagtggtt ctgacatttg ttcactcccg gttttggcca      900

agatctgcca gaaaattaaa ttagctatgg aacagtctgt gccattcaaa gatgtggatt      960

cagacaaata cagcgttttc ccaacactgc ggggctatca ctggcggggg agagactgta     1020

atgacagcga cgagtcagtg tacccaggta gaaggccgaa caactgggat gtccatcagg     1080

attcaaactg taatggcatt tggggtgtcg atccaaaaga tggagttcca tatgagaaga     1140

aattctgtga aggttcacag cccaggggaa tcattttgct gggagactca gctggggctc     1200

attttcacat ctctcctgaa tggatcacag cgtcgcagat gtctttgaac tctttcatca     1260

atctaccaac agcccttacc aacgagcttg actggcccca actctctggt gctacaggat     1320

ttctggactc cactgttgga attaaagaaa aatctattta ccttcgctta tggaaaagaa     1380

accactgtaa tcacagggac taccagaata tttcaagaaa tggtgcatct tcccgaaacc     1440

tgaagaaatt tatagaaagc ttgtctagaa acaaggtgtt ggactatccc gccatcgtta     1500

tatatgccat gattggaaat gatgtctgca gtgggaagag tgacccagtc ccagccatga     1560

ccactcctga gaaactctac tccaacgtca tgcagactct gaagcatcta aattcccacc     1620

tgcccaatgg cagccatgtt attttgtatg gcttaccaga tggaaccttt ctctgggata     1680

atttgcacaa cagatatcat cctctcggcc agctaaataa agacatgacc tatgcgcagt     1740

tgtactcctt cctgaactgc ctccaggtca gcccctgcca cggctggatg tcttccaaca     1800

agacgttgcg gactctcact tcagagagag cagagcaact ctccaacaca ctgaaaaaaa     1860

ttgcagccag tgagaaattt acaaacttca atcttttcta catggatttt gccttccatg     1920

aaatcataca ggagtggcag aagagaggcg gacagccctg gcagctcatc gagcccgtgg     1980

atggattcca ccccaacgag gtggctttgc tgttgttggc ggatcatttc tggaaaaagg     2040

tgcagctcca gtggccccaa atcctgggaa aggagaatcc gttcaacccc cagattaaac     2100

aggtgtttgg agaccaaggc gggcactgag cctctcagga gcatgcaccc ctggggagca     2160

cagggaggca gaggcttggg taaactcatt ccacaaaccc tatgggggct gccacgtcac     2220

aggcccaaag gactcttctt cagcagcatc tttgcaaaat gtctttctct caatgaagag     2280

catatctgga cgactgtgca atgctgtgtg ctcccgggat cagtaaccct tccgctgttc     2340

ctgaaataac ctttcataaa gtgctttggg tgccattcca aacaagagag tatctgtgcc     2400

ctttacagct aattgttcta aaaggagttt ctaaaaacac                           2440


<210>  7
<211>  498
<212>  PRT
<213>  Homo sapiens


<220>
<221>  SIGNAL
<222>  (1)..(15)

<400>  7

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


Ile Gly Cys Ser Asn Gln Arg Arg Ser Pro Glu Asn Ser Gly Arg Arg 
            20                  25                  30          


Tyr Asn Arg Ile Gln His Gly Gln Cys Ala Tyr Thr Phe Ile Leu Pro 
        35                  40                  45              


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


Asn Ala Leu Gln Arg Asp Ala Pro His Val Glu Pro Asp Phe Ser Ser 
65                  70                  75                  80  


Gln Lys Leu Gln His Leu Glu His Val Met Glu Asn Tyr Thr Gln Trp 
                85                  90                  95      


Leu Gln Lys Leu Glu Asn Tyr Ile Val Glu Asn Met Lys Ser Glu Met 
            100                 105                 110         


Ala Gln Ile Gln Gln Asn Ala Val Gln Asn His Thr Ala Thr Met Leu 
        115                 120                 125             


Glu Ile Gly Thr Ser Leu Leu Ser Gln Thr Ala Glu Gln Thr Arg Lys 
    130                 135                 140                 


Leu Thr Asp Val Glu Thr Gln Val Leu Asn Gln Thr Ser Arg Leu Glu 
145                 150                 155                 160 


Ile Gln Leu Leu Glu Asn Ser Leu Ser Thr Tyr Lys Leu Glu Lys Gln 
                165                 170                 175     


Leu Leu Gln Gln Thr Asn Glu Ile Leu Lys Ile His Glu Lys Asn Ser 
            180                 185                 190         


Leu Leu Glu His Lys Ile Leu Glu Met Glu Gly Lys His Lys Glu Glu 
        195                 200                 205             


Leu Asp Thr Leu Lys Glu Glu Lys Glu Asn Leu Gln Gly Leu Val Thr 
    210                 215                 220                 


Arg Gln Thr Tyr Ile Ile Gln Glu Leu Glu Lys Gln Leu Asn Arg Ala 
225                 230                 235                 240 


Thr Thr Asn Asn Ser Val Leu Gln Lys Gln Gln Leu Glu Leu Met Asp 
                245                 250                 255     


Thr Val His Asn Leu Val Asn Leu Cys Thr Lys Glu Gly Val Leu Leu 
            260                 265                 270         


Lys Gly Gly Lys Arg Glu Glu Glu Lys Pro Phe Arg Asp Cys Ala Asp 
        275                 280                 285             


Val Tyr Gln Ala Gly Phe Asn Lys Ser Gly Ile Tyr Thr Ile Tyr Ile 
    290                 295                 300                 


Asn Asn Met Pro Glu Pro Lys Lys Val Phe Cys Asn Met Asp Val Asn 
305                 310                 315                 320 


Gly Gly Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser Leu Asp 
                325                 330                 335     


Phe Gln Arg Gly Trp Lys Glu Tyr Lys Met Gly Phe Gly Asn Pro Ser 
            340                 345                 350         


Gly Glu Tyr Trp Leu Gly Asn Glu Phe Ile Phe Ala Ile Thr Ser Gln 
        355                 360                 365             


Arg Gln Tyr Met Leu Arg Ile Glu Leu Met Asp Trp Glu Gly Asn Arg 
    370                 375                 380                 


Ala Tyr Ser Gln Tyr Asp Arg Phe His Ile Gly Asn Glu Lys Gln Asn 
385                 390                 395                 400 


Tyr Arg Leu Tyr Leu Lys Gly His Thr Gly Thr Ala Gly Lys Gln Ser 
                405                 410                 415     


Ser Leu Ile Leu His Gly Ala Asp Phe Ser Thr Lys Asp Ala Asp Asn 
            420                 425                 430         


Asp Asn Cys Met Cys Lys Cys Ala Leu Met Leu Thr Gly Gly Trp Trp 
        435                 440                 445             


Phe Asp Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Phe Tyr Thr Ala 
    450                 455                 460                 


Gly Gln Asn His Gly Lys Leu Asn Gly Ile Lys Trp His Tyr Phe Lys 
465                 470                 475                 480 


Gly Pro Ser Tyr Ser Leu Arg Ser Thr Thr Met Met Ile Arg Pro Leu 
                485                 490                 495     


Asp Phe 
        


<210>  8
<211>  4367
<212>  DNA
<213>  Homo sapiens

<400>  8
gccctaagcc atcagcaatc cttagtatag gggcacactc atgcattcct gtcaagtcat       60

cttgtgaaag gctgcctgct tccagcttgg cttggatgtg caaccttaat aaaactcact      120

gaggtctggg agaaaatagc agatctgcag cagatagggt agaggaaagg gtctagaata      180

tgtacacgca gctgactcag gcaggctcca tgctgaacgg tcacacagag aggaaacaat      240

aaatctcagc tactatgcaa taaatatctc aagttttaac gaagaaaaac atcattgcag      300

tgaaataaaa aattttaaaa ttttagaaca aagctaacaa atggctagtt ttctatgatt      360

cttcttcaaa cgctttcttt gagggggaaa gagtcaaaca aacaagcagt tttacctgaa      420

ataaagaact agttttagag gtcagaagaa aggagcaagt tttgcgagag gcacggaagg      480

agtgtgctgg cagtacaatg acagttttcc tttcctttgc tttcctcgct gccattctga      540

ctcacatagg gtgcagcaat cagcgccgaa gtccagaaaa cagtgggaga agatataacc      600

ggattcaaca tgggcaatgt gcctacactt tcattcttcc agaacacgat ggcaactgtc      660

gtgagagtac gacagaccag tacaacacaa acgctctgca gagagatgct ccacacgtgg      720

aaccggattt ctcttcccag aaacttcaac atctggaaca tgtgatggaa aattatactc      780

agtggctgca aaaacttgag aattacattg tggaaaacat gaagtcggag atggcccaga      840

tacagcagaa tgcagttcag aaccacacgg ctaccatgct ggagatagga accagcctcc      900

tctctcagac tgcagagcag accagaaagc tgacagatgt tgagacccag gtactaaatc      960

aaacttctcg acttgagata cagctgctgg agaattcatt atccacctac aagctagaga     1020

agcaacttct tcaacagaca aatgaaatct tgaagatcca tgaaaaaaac agtttattag     1080

aacataaaat cttagaaatg gaaggaaaac acaaggaaga gttggacacc ttaaaggaag     1140

agaaagagaa ccttcaaggc ttggttactc gtcaaacata tataatccag gagctggaaa     1200

agcaattaaa cagagctacc accaacaaca gtgtccttca gaagcagcaa ctggagctga     1260

tggacacagt ccacaacctt gtcaatcttt gcactaaaga aggtgtttta ctaaagggag     1320

gaaaaagaga ggaagagaaa ccatttagag actgtgcaga tgtatatcaa gctggtttta     1380

ataaaagtgg aatctacact atttatatta ataatatgcc agaacccaaa aaggtgtttt     1440

gcaatatgga tgtcaatggg ggaggttgga ctgtaataca acatcgtgaa gatggaagtc     1500

tagatttcca aagaggctgg aaggaatata aaatgggttt tggaaatccc tccggtgaat     1560

attggctggg gaatgagttt atttttgcca ttaccagtca gaggcagtac atgctaagaa     1620

ttgagttaat ggactgggaa gggaaccgag cctattcaca gtatgacaga ttccacatag     1680

gaaatgaaaa gcaaaactat aggttgtatt taaaaggtca cactgggaca gcaggaaaac     1740

agagcagcct gatcttacac ggtgctgatt tcagcactaa agatgctgat aatgacaact     1800

gtatgtgcaa atgtgccctc atgttaacag gaggatggtg gtttgatgct tgtggcccct     1860

ccaatctaaa tggaatgttc tatactgcgg gacaaaacca tggaaaactg aatgggataa     1920

agtggcacta cttcaaaggg cccagttact ccttacgttc cacaactatg atgattcgac     1980

ctttagattt ttgaaagcgc aatgtcagaa gcgattatga aagcaacaaa gaaatccgga     2040

gaagctgcca ggtgagaaac tgtttgaaaa cttcagaagc aaacaatatt gtctcccttc     2100

cagcaataag tggtagttat gtgaagtcac caaggttctt gaccgtgaat ctggagccgt     2160

ttgagttcac aagagtctct acttggggtg acagtgctca cgtggctcga ctatagaaaa     2220

ctccactgac tgtcgggctt taaaaaggga agaaactgct gagcttgctg tgcttcaaac     2280

tactactgga ccttattttg gaactatggt agccagatga taaatatggt taatttcatg     2340

taaaacagaa aaaaagagtg aaaaagagaa tatacatgaa gaatagaaac aagcctgcca     2400

taatcctttg gaaaagatgt attataccag tgaaaaggtg ttatatctat gcaaacctac     2460

taacaaatta tactgttgca caattttgat aaaaatttag aacagcattg tcctctgagt     2520

tggttaaatg ttaatggatt tcagaagcct aattccagta tcatacttac tagttgattt     2580

ctgcttaccc atcttcaaat gaaaattcca tttttgtaag ccataatgaa ctgtagtaca     2640

tggacaataa gtgtgtggta gaaacaaact ccattactct gatttttgat acagttttca     2700

gaaaaagaaa tgaacataat caagtaagga tgtatgtggt gaaaacttac cacccccata     2760

ctatggtttt catttactct aaaaactgat tgaatgatat ataaatatat ttatagcctg     2820

agtaaagtta aaagaatgta aaatatatca tcaagttctt aaaataatat acatgcattt     2880

aatatttcct ttgatattat acaggaaagc aatattttgg agtatgttaa gttgaagtaa     2940

aagcaagtac tctggagcag ttcattttac agtatctact tgcatgtgta tacatacatg     3000

taacttcatt attttaaaaa tatttttaga actccaatac tcaccctgtt atgtcttgct     3060

aatttaaatt ttgctaatta actgaaacat gcttaccaga ttcacactgt tccagtgtct     3120

ataaaagaaa cactttgaag tctataaaaa ataaaataat tataaatatc attgtacata     3180

gcatgtttat atctgcaaaa aacctaatag ctaattaatc tggaatatgc aacattgtcc     3240

ttaattgatg caaataacac aaatgctcaa agaaatctac tatatccctt aatgaaatac     3300

atcattcttc atatatttct ccttcagtcc attcccttag gcaattttta atttttaaaa     3360

attattatca ggggagaaaa attggcaaaa ctattatatg taagggaaat atatacaaaa     3420

agaaaattaa tcatagtcac ctgactaaga aattctgact gctagttgcc ataaataact     3480

caatggaaat attcctatgg gataatgtat tttaagtgaa tttttggggt gcttgaagtt     3540

actgcattat tttatcaaga agtcttctct gcctgtaagt gtccaaggtt atgacagtaa     3600

acagttttta ttaaaacatg agtcactatg ggatgagaaa attgaaataa agctactggg     3660

cctcctctca taaaagagac agttgttggc aaggtagcaa taccagtttc aaacttggtg     3720

acttgatcca ctatgcctta atggtttcct ccatttgaga aaataaagct attcacattg     3780

ttaagaaaaa tactttttaa agtttaccat caagtctttt ttatatttat gtgtctgtat     3840

tctacccctt tttgccttac aagtgatatt tgcaggtatt ataccatttt tctattcttg     3900

gtggcttctt catagcaggt aagcctctcc ttctaaaaac ttctcaactg ttttcattta     3960

agggaaagaa aatgagtatt ttgtcctttt gtgttcctac agacactttc ttaaaccagt     4020

ttttggataa agaatactat ttccaaactc atattacaaa aacaaaataa aataataaaa     4080

aaagaaagca tgatatttac tgttttgttg tctgggtttg agaaatgaaa tattgtttcc     4140

aattatttat aataaatcag tataaaatgt tttatgattg ttatgtgtat tatgtaatac     4200

gtacatgttt atggcaattt aacatgtgta ttcttttaat tgtttcagaa taggataatt     4260

aggtattcga attttgtctt taaaattcat gtggtttcta tgcaaagttc ttcatatcat     4320

cacaacatta tttgatttaa ataaaattga aagtaatatt tgtgcaa                   4367


