                               SEQUENCE LISTING

<110> THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
 
<120> METHODS AND COMPOSITIONS RELATING TO TREATMENT OF PULMONARY 
      ARTERIAL HYPERTENSION

<130> 043214-082451-PCT

<140> PCT/US2015/043373
<141> 2015-08-03

<150> 62/031,924
<151> 2014-08-01

<160> 4     

<170> PatentIn version 3.5

<210> 1
<211> 308
<212> PRT
<213> Homo sapiens

<400> 1
Met Pro Gly Gln Glu Leu Arg Thr Val Asn Gly Ser Gln Met Leu Leu 
1               5                   10                  15      


Val Leu Leu Val Leu Ser Trp Leu Pro His Gly Gly Ala Leu Ser Leu 
            20                  25                  30          


Ala Glu Ala Ser Arg Ala Ser Phe Pro Gly Pro Ser Glu Leu His Ser 
        35                  40                  45              


Glu Asp Ser Arg Phe Arg Glu Leu Arg Lys Arg Tyr Glu Asp Leu Leu 
    50                  55                  60                  


Thr Arg Leu Arg Ala Asn Gln Ser Trp Glu Asp Ser Asn Thr Asp Leu 
65                  70                  75                  80  


Val Pro Ala Pro Ala Val Arg Ile Leu Thr Pro Glu Val Arg Leu Gly 
                85                  90                  95      


Ser Gly Gly His Leu His Leu Arg Ile Ser Arg Ala Ala Leu Pro Glu 
            100                 105                 110         


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


Pro Thr Ala Ser Arg Ser Trp Asp Val Thr Arg Pro Leu Arg Arg Gln 
    130                 135                 140                 


Leu Ser Leu Ala Arg Pro Gln Ala Pro Ala Leu His Leu Arg Leu Ser 
145                 150                 155                 160 


Pro Pro Pro Ser Gln Ser Asp Gln Leu Leu Ala Glu Ser Ser Ser Ala 
                165                 170                 175     


Arg Pro Gln Leu Glu Leu His Leu Arg Pro Gln Ala Ala Arg Gly Arg 
            180                 185                 190         


Arg Arg Ala Arg Ala Arg Asn Gly Asp His Cys Pro Leu Gly Pro Gly 
        195                 200                 205             


Arg Cys Cys Arg Leu His Thr Val Arg Ala Ser Leu Glu Asp Leu Gly 
    210                 215                 220                 


Trp Ala Asp Trp Val Leu Ser Pro Arg Glu Val Gln Val Thr Met Cys 
225                 230                 235                 240 


Ile Gly Ala Cys Pro Ser Gln Phe Arg Ala Ala Asn Met His Ala Gln 
                245                 250                 255     


Ile Lys Thr Ser Leu His Arg Leu Lys Pro Asp Thr Val Pro Ala Pro 
            260                 265                 270         


Cys Cys Val Pro Ala Ser Tyr Asn Pro Met Val Leu Ile Gln Lys Thr 
        275                 280                 285             


Asp Thr Gly Val Ser Leu Gln Thr Tyr Asp Asp Leu Leu Ala Lys Asp 
    290                 295                 300                 


Cys His Cys Ile 
305             


<210> 2
<211> 390
<212> PRT
<213> Homo sapiens

<400> 2
Met Pro Pro Ser Gly Leu Arg Leu Leu Pro Leu Leu Leu Pro Leu Leu 
1               5                   10                  15      


Trp Leu Leu Val Leu Thr Pro Gly Arg Pro Ala Ala Gly Leu Ser Thr 
            20                  25                  30          


Cys Lys Thr Ile Asp Met Glu Leu Val Lys Arg Lys Arg Ile Glu Ala 
        35                  40                  45              


Ile Arg Gly Gln Ile Leu Ser Lys Leu Arg Leu Ala Ser Pro Pro Ser 
    50                  55                  60                  


Gln Gly Glu Val Pro Pro Gly Pro Leu Pro Glu Ala Val Leu Ala Leu 
65                  70                  75                  80  


Tyr Asn Ser Thr Arg Asp Arg Val Ala Gly Glu Ser Ala Glu Pro Glu 
                85                  90                  95      


Pro Glu Pro Glu Ala Asp Tyr Tyr Ala Lys Glu Val Thr Arg Val Leu 
            100                 105                 110         


Met Val Glu Thr His Asn Glu Ile Tyr Asp Lys Phe Lys Gln Ser Thr 
        115                 120                 125             


His Ser Ile Tyr Met Phe Phe Asn Thr Ser Glu Leu Arg Glu Ala Val 
    130                 135                 140                 


Pro Glu Pro Val Leu Leu Ser Arg Ala Glu Leu Arg Leu Leu Arg Leu 
145                 150                 155                 160 


Lys Leu Lys Val Glu Gln His Val Glu Leu Tyr Gln Lys Tyr Ser Asn 
                165                 170                 175     


Asn Ser Trp Arg Tyr Leu Ser Asn Arg Leu Leu Ala Pro Ser Asp Ser 
            180                 185                 190         


Pro Glu Trp Leu Ser Phe Asp Val Thr Gly Val Val Arg Gln Trp Leu 
        195                 200                 205             


Ser Arg Gly Gly Glu Ile Glu Gly Phe Arg Leu Ser Ala His Cys Ser 
    210                 215                 220                 


Cys Asp Ser Arg Asp Asn Thr Leu Gln Val Asp Ile Asn Gly Phe Thr 
225                 230                 235                 240 


Thr Gly Arg Arg Gly Asp Leu Ala Thr Ile His Gly Met Asn Arg Pro 
                245                 250                 255     


Phe Leu Leu Leu Met Ala Thr Pro Leu Glu Arg Ala Gln His Leu Gln 
            260                 265                 270         


Ser Ser Arg His Arg Arg Ala Leu Asp Thr Asn Tyr Cys Phe Ser Ser 
        275                 280                 285             


Thr Glu Lys Asn Cys Cys Val Arg Gln Leu Tyr Ile Asp Phe Arg Lys 
    290                 295                 300                 


Asp Leu Gly Trp Lys Trp Ile His Glu Pro Lys Gly Tyr His Ala Asn 
305                 310                 315                 320 


Phe Cys Leu Gly Pro Cys Pro Tyr Ile Trp Ser Leu Asp Thr Gln Tyr 
                325                 330                 335     


Ser Lys Val Leu Ala Leu Tyr Asn Gln His Asn Pro Gly Ala Ser Ala 
            340                 345                 350         


Ala Pro Cys Cys Val Pro Gln Ala Leu Glu Pro Leu Pro Ile Val Tyr 
        355                 360                 365             


Tyr Val Gly Arg Lys Pro Lys Val Glu Gln Leu Ser Asn Met Ile Val 
    370                 375                 380                 


Arg Ser Cys Lys Cys Ser 
385                 390 


<210> 3
<211> 412
<212> PRT
<213> Homo sapiens

<400> 3
Met Lys Met His Leu Gln Arg Ala Leu Val Val Leu Ala Leu Leu Asn 
1               5                   10                  15      


Phe Ala Thr Val Ser Leu Ser Leu Ser Thr Cys Thr Thr Leu Asp Phe 
            20                  25                  30          


Gly His Ile Lys Lys Lys Arg Val Glu Ala Ile Arg Gly Gln Ile Leu 
        35                  40                  45              


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


Val Pro Tyr Gln Val Leu Ala Leu Tyr Asn Ser Thr Arg Glu Leu Leu 
65                  70                  75                  80  


Glu Glu Met His Gly Glu Arg Glu Glu Gly Cys Thr Gln Glu Asn Thr 
                85                  90                  95      


Glu Ser Glu Tyr Tyr Ala Lys Glu Ile His Lys Phe Asp Met Ile Gln 
            100                 105                 110         


Gly Leu Ala Glu His Asn Glu Leu Ala Val Cys Pro Lys Gly Ile Thr 
        115                 120                 125             


Ser Lys Val Phe Arg Phe Asn Val Ser Ser Val Glu Lys Asn Arg Thr 
    130                 135                 140                 


Asn Leu Phe Arg Ala Glu Phe Arg Val Leu Arg Val Pro Asn Pro Ser 
145                 150                 155                 160 


Ser Lys Arg Asn Glu Gln Arg Ile Glu Leu Phe Gln Ile Leu Arg Pro 
                165                 170                 175     


Asp Glu His Ile Ala Lys Gln Arg Tyr Ile Gly Gly Lys Asn Leu Pro 
            180                 185                 190         


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


Arg Glu Trp Leu Leu Arg Arg Glu Ser Asn Leu Gly Leu Glu Ile Ser 
    210                 215                 220                 


Ile His Cys Pro Cys His Thr Phe Gln Pro Asn Gly Asp Ile Leu Glu 
225                 230                 235                 240 


Asn Ile His Glu Val Met Glu Ile Lys Phe Lys Gly Val Asp Asn Glu 
                245                 250                 255     


Asp Asp His Gly Arg Gly Asp Leu Gly Arg Leu Lys Lys Gln Lys Asp 
            260                 265                 270         


His His Asn Pro His Leu Ile Leu Met Met Ile Pro Pro His Arg Leu 
        275                 280                 285             


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


Asn Tyr Cys Phe Arg Asn Leu Glu Glu Asn Cys Cys Val Arg Pro Leu 
305                 310                 315                 320 


Tyr Ile Asp Phe Arg Gln Asp Leu Gly Trp Lys Trp Val His Glu Pro 
                325                 330                 335     


Lys Gly Tyr Tyr Ala Asn Phe Cys Ser Gly Pro Cys Pro Tyr Leu Arg 
            340                 345                 350         


Ser Ala Asp Thr Thr His Ser Thr Val Leu Gly Leu Tyr Asn Thr Leu 
        355                 360                 365             


Asn Pro Glu Ala Ser Ala Ser Pro Cys Cys Val Pro Gln Asp Leu Glu 
    370                 375                 380                 


Pro Leu Thr Ile Leu Tyr Tyr Val Gly Arg Thr Pro Lys Val Glu Gln 
385                 390                 395                 400 


Leu Ser Asn Met Val Val Lys Ser Cys Lys Cys Ser 
                405                 410         


<210> 4
<211> 592
<212> PRT
<213> Homo sapiens

<400> 4
Met Gly Arg Gly Leu Leu Arg Gly Leu Trp Pro Leu His Ile Val Leu 
1               5                   10                  15      


Trp Thr Arg Ile Ala Ser Thr Ile Pro Pro His Val Gln Lys Ser Asp 
            20                  25                  30          


Val Glu Met Glu Ala Gln Lys Asp Glu Ile Ile Cys Pro Ser Cys Asn 
        35                  40                  45              


Arg Thr Ala His Pro Leu Arg His Ile Asn Asn Asp Met Ile Val Thr 
    50                  55                  60                  


Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp 
65                  70                  75                  80  


Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys 
                85                  90                  95      


Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val 
            100                 105                 110         


Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp 
        115                 120                 125             


Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro 
    130                 135                 140                 


Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met 
145                 150                 155                 160 


Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu 
                165                 170                 175     


Glu Tyr Asn Thr Ser Asn Pro Asp Leu Leu Leu Val Ile Phe Gln Val 
            180                 185                 190         


Thr Gly Ile Ser Leu Leu Pro Pro Leu Gly Val Ala Ile Ser Val Ile 
        195                 200                 205             


Ile Ile Phe Tyr Cys Tyr Arg Val Asn Arg Gln Gln Lys Leu Ser Ser 
    210                 215                 220                 


Thr Trp Glu Thr Gly Lys Thr Arg Lys Leu Met Glu Phe Ser Glu His 
225                 230                 235                 240 


Cys Ala Ile Ile Leu Glu Asp Asp Arg Ser Asp Ile Ser Ser Thr Cys 
                245                 250                 255     


Ala Asn Asn Ile Asn His Asn Thr Glu Leu Leu Pro Ile Glu Leu Asp 
            260                 265                 270         


Thr Leu Val Gly Lys Gly Arg Phe Ala Glu Val Tyr Lys Ala Lys Leu 
        275                 280                 285             


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


Pro Tyr Glu Glu Tyr Ala Ser Trp Lys Thr Glu Lys Asp Ile Phe Ser 
305                 310                 315                 320 


Asp Ile Asn Leu Lys His Glu Asn Ile Leu Gln Phe Leu Thr Ala Glu 
                325                 330                 335     


Glu Arg Lys Thr Glu Leu Gly Lys Gln Tyr Trp Leu Ile Thr Ala Phe 
            340                 345                 350         


His Ala Lys Gly Asn Leu Gln Glu Tyr Leu Thr Arg His Val Ile Ser 
        355                 360                 365             


Trp Glu Asp Leu Arg Lys Leu Gly Ser Ser Leu Ala Arg Gly Ile Ala 
    370                 375                 380                 


His Leu His Ser Asp His Thr Pro Cys Gly Arg Pro Lys Met Pro Ile 
385                 390                 395                 400 


Val His Arg Asp Leu Lys Ser Ser Asn Ile Leu Val Lys Asn Asp Leu 
                405                 410                 415     


Thr Cys Cys Leu Cys Asp Phe Gly Leu Ser Leu Arg Leu Asp Pro Thr 
            420                 425                 430         


Leu Ser Val Asp Asp Leu Ala Asn Ser Gly Gln Val Gly Thr Ala Arg 
        435                 440                 445             


Tyr Met Ala Pro Glu Val Leu Glu Ser Arg Met Asn Leu Glu Asn Val 
    450                 455                 460                 


Glu Ser Phe Lys Gln Thr Asp Val Tyr Ser Met Ala Leu Val Leu Trp 
465                 470                 475                 480 


Glu Met Thr Ser Arg Cys Asn Ala Val Gly Glu Val Lys Asp Tyr Glu 
                485                 490                 495     


Pro Pro Phe Gly Ser Lys Val Arg Glu His Pro Cys Val Glu Ser Met 
            500                 505                 510         


Lys Asp Asn Val Leu Arg Asp Arg Gly Arg Pro Glu Ile Pro Ser Phe 
        515                 520                 525             


Trp Leu Asn His Gln Gly Ile Gln Met Val Cys Glu Thr Leu Thr Glu 
    530                 535                 540                 


Cys Trp Asp His Asp Pro Glu Ala Arg Leu Thr Ala Gln Cys Val Ala 
545                 550                 555                 560 


Glu Arg Phe Ser Glu Leu Glu His Leu Asp Arg Leu Ser Gly Arg Ser 
                565                 570                 575     


Cys Ser Glu Glu Lys Ile Pro Glu Asp Gly Ser Leu Asn Thr Thr Lys 
            580                 585                 590         


