               SEQUENCE LISTING

<110> DERMA INNOVATE S.L.
      FUNDACIN PARA LA INVESTIGACIN BIOMDICA DEL HOSPITAL UNIVERSITARIO RAMN Y CAJAL

<120> SRC KINASE ACTIVATORS AND ENG FUNCTION INHIBITORS
AS ENHANCERS OF SKIN HOMEOSTASIS/REGENERATION
AND HAIR GROWTH.

<130> 905 980

<140> EP20382337.2
<141> 2020-04-24

<160> 8

<170> BiSSAP 1.3.6

<210> 1
<211> 11
<212> PRT
<213> Artificial Sequence


<220> 
<223> YEEI peptide

<220> 
<221> VARIANT
<222> 4
<223> x = Tyr(PO3H2)

<400> 1
Glu Pro Gln Xaa Glu Glu Ile Pro Ile Tyr Leu 
1               5                   10      

<210> 2
<211> 425
<212> RNA
<213> Artificial Sequence


<220> 
<223> siRNA targeting the mRNA of human Eng

<400> 2
catgcagatc tggaccactg gagaatactc cttcaagatc tttccagaga aaaacattcg      60

tggcttcaag ctcccagaca cacctcaagg cctcctgggg gaggcccgga tgctcaatgc     120

cagcattgtg gcatccttcg tggagctacc gctggccagc attgtctcac ttcatgcctc     180

cagctgcggt ggtaggctgc agacctcacc cgcaccgatc cagaccactc ctcccaagga     240

cacttgtagc ccggagctgc tcatgtcctt gatccagaca aagtgtgccg acgacgccat     300

gaccctggta ctaaagaaag agcttgttgc gcatttgaag tgcaccatca cgggcctgac     360

cttctgggac cccagctgtg aggcagagga caggggtgac aagtttgtct tgcgcagtgc     420

ttact                                                                 425


<210> 3
<211> 76
<212> DNA
<213> Artificial Sequence


<220> 
<223> Aptamer1

<400> 3
gcggatgaag actggtgtgg gtgggtgggt gggaaggcgg caggctttgg ttcgctgggc     60

cctaaatacg agcaac                                                     76


<210> 4
<211> 60
<212> DNA
<213> Artificial Sequence


<220> 
<223> Aptamer 2

<400> 4
cccccgatgc tttcgctttt cctttcgctt ttgttcgctt cgtccctgct tcctttcttg     60


<210> 5
<211> 565
<212> PRT
<213> Artificial Sequence


<220> 
<223> RECOMBINANT GLYCOSYLATED POLYPEPTIDE ENCOMPASSING THE SOLUBLE
      EXTRACELLULAR DOMAIN OF THE HUMAN ENG PROTEIN (S-ENDOGLIN)

<400> 5
Glu Thr Val His Cys Asp Leu Gln Pro Val Gly Pro Glu Arg Gly Glu 
1               5                   10                  15      
Val Thr Tyr Thr Thr Ser Gln Val Ser Lys Gly Cys Val Ala Gln Ala 
            20                  25                  30          
Pro Asn Ala Ile Leu Glu Val His Val Leu Phe Leu Glu Phe Pro Thr 
        35                  40                  45              
Gly Pro Ser Gln Leu Glu Leu Thr Leu Gln Ala Ser Lys Gln Asn Gly 
    50                  55                  60                  
Thr Trp Pro Arg Glu Val Leu Leu Val Leu Ser Val Asn Ser Ser Val 
65                  70                  75                  80  
Phe Leu His Leu Gln Ala Leu Gly Ile Pro Leu His Leu Ala Tyr Asn 
                85                  90                  95      
Ser Ser Leu Val Thr Phe Gln Glu Pro Pro Gly Val Asn Thr Thr Glu 
            100                 105                 110         
Leu Pro Ser Phe Pro Lys Thr Gln Ile Leu Glu Trp Ala Ala Glu Arg 
        115                 120                 125             
Gly Pro Ile Thr Ser Ala Ala Glu Leu Asn Asp Pro Gln Ser Ile Leu 
    130                 135                 140                 
Leu Arg Leu Gly Gln Ala Gln Gly Ser Leu Ser Phe Cys Met Leu Glu 
145                 150                 155                 160 
Ala Ser Gln Asp Met Gly Arg Thr Leu Glu Trp Arg Pro Arg Thr Pro 
                165                 170                 175     
Ala Leu Val Arg Gly Cys His Leu Glu Gly Val Ala Gly His Lys Glu 
            180                 185                 190         
Ala His Ile Leu Arg Val Leu Pro Gly His Ser Ala Gly Pro Arg Thr 
        195                 200                 205             
Val Thr Val Lys Val Glu Leu Ser Cys Ala Pro Gly Asp Leu Asp Ala 
    210                 215                 220                 
Val Leu Ile Leu Gln Gly Pro Pro Tyr Val Ser Trp Leu Ile Asp Ala 
225                 230                 235                 240 
Asn His Asn Met Gln Ile Trp Thr Thr Gly Glu Tyr Ser Phe Lys Ile 
                245                 250                 255     
Phe Pro Glu Lys Asn Ile Arg Gly Phe Lys Leu Pro Asp Thr Pro Gln 
            260                 265                 270         
Gly Leu Leu Gly Glu Ala Arg Met Leu Asn Ala Ser Ile Val Ala Ser 
        275                 280                 285             
Phe Val Glu Leu Pro Leu Ala Ser Ile Val Ser Leu His Ala Ser Ser 
    290                 295                 300                 
Cys Gly Gly Arg Leu Gln Thr Ser Pro Ala Pro Ile Gln Thr Thr Pro 
305                 310                 315                 320 
Pro Lys Asp Thr Cys Ser Pro Glu Leu Leu Met Ser Leu Ile Gln Thr 
                325                 330                 335     
Lys Cys Ala Asp Asp Ala Met Thr Leu Val Leu Lys Lys Glu Leu Val 
            340                 345                 350         
Ala His Leu Lys Cys Thr Ile Thr Gly Leu Thr Phe Trp Asp Pro Ser 
        355                 360                 365             
Cys Glu Ala Glu Asp Arg Gly Asp Lys Phe Val Leu Arg Ser Ala Tyr 
    370                 375                 380                 
Ser Ser Cys Gly Met Gln Val Ser Ala Ser Met Ile Ser Asn Glu Ala 
385                 390                 395                 400 
Val Val Asn Ile Leu Ser Ser Ser Ser Pro Gln Arg Lys Lys Val His 
                405                 410                 415     
Cys Leu Asn Met Asp Ser Leu Ser Phe Gln Leu Gly Leu Tyr Leu Ser 
            420                 425                 430         
Pro His Phe Leu Gln Ala Ser Asn Thr Ile Glu Pro Gly Gln Gln Ser 
        435                 440                 445             
Phe Val Gln Val Arg Val Ser Pro Ser Val Ser Glu Phe Leu Leu Gln 
    450                 455                 460                 
Leu Asp Ser Cys His Leu Asp Leu Gly Pro Glu Gly Gly Thr Val Glu 
465                 470                 475                 480 
Leu Ile Gln Gly Arg Ala Ala Lys Gly Asn Cys Val Ser Leu Leu Ser 
                485                 490                 495     
Pro Ser Pro Glu Gly Asp Pro Arg Phe Ser Phe Leu Leu His Phe Tyr 
            500                 505                 510         
Thr Val Pro Ile Pro Lys Thr Gly Thr Leu Ser Cys Thr Val Ala Leu 
        515                 520                 525             
Arg Pro Lys Thr Gly Ser Gln Asp Gln Glu Val His Arg Thr Val Phe 
    530                 535                 540                 
Met Arg Leu Asn Ile Ile Ser Pro Asp Leu Ser Gly Cys Thr Ser His 
545                 550                 555                 560 
His His His His His 
                565 

<210> 6
<211> 1311
<212> DNA
<213> Homo sapiens


<220> 
<223> Predicted cDNA sequence of soluble endoglin

<400> 6
atggaccgcg gcacgctccc tctggctgtt gccctgctgc tggccagctg cagcctcagc      60

cccacaagtc ttgcagaaac agtccattgt gaccttcagc ctgtgggccc cgagagggac     120

gaggtgacat ataccactag ccaggtctcg aagggctgcg tggctcaggc ccccaatgcc     180

atccttgaag tccatgtcct cttcctggag ttcccaacgg gcccgtcaca gctggagctg     240

actctccagg catccaagca aaatggcacc tggccccgag aggtgcttct ggtcctcagt     300

gtaaacagca gtgtcttcct gcatctccag gccctgggaa tcccactgca cttggcctac     360

aattccagcc tggtcacctt ccaagagccc ccgggggtca acaccacaga gctgccatcc     420

ttccccaaga cccagatcct tgagtgggca gctgagaggg gccccatcac ctctgctgct     480

gagctgaatg acccccagag catcctcctc cgactgggcc aagcccaggg gtcactgtcc     540

ttctgcatgc tggaagccag ccaggacatg ggccgcacgc tcgagtggcg gccgcgtact     600

ccagccttgg tccggggctg ccacttggaa ggcgtggccg gccacaagga ggcgcacatc     660

ctgagggtcc tgccgggcca ctcggccggg ccccggacgg tgacggtgaa ggtggaactg     720

agctgcgcac ccggggatct cgatgccgtc ctcatcctgc agggtccccc ctacgtgtcc     780

tggctcatcg acgccaacca caacatgcag atctggacca ctggagaata ctccttcaag     840

atctttccag agaaaaacat tcgtggcttc aagctcccag acacacctca aggcctcctg     900

ggggaggccc ggatgctcaa tgccagcatt gtggcatcct tcgtggagct accgctggcc     960

agcattgtct cacttcatgc ctccagctgc ggtggtaggc tgcagacctc acccgcaccg    1020

atccagacca ctcctcccaa ggacacttgt agcccggagc tgctcatgtc cttgatccag    1080

acaaagtgtg ccgacgacgc catgaccctg gtactaaaga aagagcttgt tgcgcatttg    1140

aagtgcacca tcacgggcct gaccttctgg gaccccagct gtgaggcaga ggacaggggt    1200

gacaagtttg tcttgcgcag tgcttactcc agctgtggca tgcaggtgtc agcaagtatg    1260

atcagcaatg aggcggtggt caatatcctg tcgagctcat caccacagcg g             1311


<210> 7
<211> 437
<212> PRT
<213> Homo sapiens


<220> 
<223> Predicted protein sequence endoglin polypeptide

<400> 7
Met Asp Arg Gly Thr Leu Pro Leu Ala Val Ala Leu Leu Leu Ala Ser 
1               5                   10                  15      
Cys Ser Leu Ser Pro Thr Ser Leu Ala Glu Thr Val His Cys Asp Leu 
            20                  25                  30          
Gln Pro Val Gly Pro Glu Arg Gly Glu Val Thr Tyr Thr Thr Ser Gln 
        35                  40                  45              
Val Ser Lys Gly Cys Val Ala Gln Ala Pro Asn Ala Ile Leu Glu Val 
    50                  55                  60                  
His Val Leu Phe Leu Glu Phe Pro Thr Gly Pro Ser Gln Leu Glu Leu 
65                  70                  75                  80  
Thr Leu Gln Ala Ser Lys Gln Asn Gly Thr Trp Pro Arg Glu Val Leu 
                85                  90                  95      
Leu Val Leu Ser Val Asn Ser Ser Val Phe Leu His Leu Gln Ala Leu 
            100                 105                 110         
Gly Ile Pro Leu His Leu Ala Tyr Asn Ser Ser Leu Val Thr Phe Gln 
        115                 120                 125             
Glu Pro Pro Gly Val Asn Thr Thr Glu Leu Pro Ser Phe Pro Lys Thr 
    130                 135                 140                 
Gln Ile Leu Glu Trp Ala Ala Glu Arg Gly Pro Ile Thr Ser Ala Ala 
145                 150                 155                 160 
Glu Leu Asn Asp Pro Gln Ser Ile Leu Leu Arg Leu Gly Gln Ala Gln 
                165                 170                 175     
Gly Ser Leu Ser Phe Cys Met Leu Glu Ala Ser Gln Asp Met Gly Arg 
            180                 185                 190         
Thr Leu Glu Trp Arg Pro Arg Thr Pro Ala Leu Val Arg Gly Cys His 
        195                 200                 205             
Leu Glu Gly Val Ala Gly His Lys Glu Ala His Ile Leu Arg Val Leu 
    210                 215                 220                 
Pro Gly His Ser Ala Gly Pro Arg Thr Val Thr Val Lys Val Glu Leu 
225                 230                 235                 240 
Ser Cys Ala Pro Gly Asp Leu Asp Ala Val Leu Ile Leu Gln Gly Pro 
                245                 250                 255     
Pro Tyr Val Ser Trp Leu Ile Asp Ala Asn His Asn Met Gln Ile Trp 
            260                 265                 270         
Thr Thr Gly Glu Tyr Ser Phe Lys Ile Phe Pro Glu Lys Asn Ile Arg 
        275                 280                 285             
Gly Phe Lys Leu Pro Asp Thr Pro Gln Gly Leu Leu Gly Glu Ala Arg 
    290                 295                 300                 
Met Leu Asn Ala Ser Ile Val Ala Ser Phe Val Glu Leu Pro Leu Ala 
305                 310                 315                 320 
Ser Ile Val Ser Leu His Ala Ser Ser Cys Gly Gly Arg Leu Gln Thr 
                325                 330                 335     
Ser Pro Ala Pro Ile Gln Thr Thr Pro Pro Lys Asp Thr Cys Ser Pro 
            340                 345                 350         
Glu Leu Leu Met Ser Leu Ile Gln Thr Lys Cys Ala Asp Asp Ala Met 
        355                 360                 365             
Thr Leu Val Leu Lys Lys Glu Leu Val Ala His Leu Lys Cys Thr Ile 
    370                 375                 380                 
Thr Gly Leu Thr Phe Trp Asp Pro Ser Cys Glu Ala Glu Asp Arg Gly 
385                 390                 395                 400 
Asp Lys Phe Val Leu Arg Ser Ala Tyr Ser Ser Cys Gly Met Gln Val 
                405                 410                 415     
Ser Ala Ser Met Ile Ser Asn Glu Ala Val Val Asn Ile Leu Ser Ser 
            420                 425                 430         
Ser Ser Pro Gln Arg 
        435         

<210> 8
<211> 632
<212> PRT
<213> Homo sapiens


<220> 
<223> Additional forms of soluble endoglin

<400> 8
Glu Thr Val His Cys Asp Leu Gln Pro Val Gly Pro Glu Arg Gly Glu 
1               5                   10                  15      
Val Thr Tyr Thr Thr Ser Gln Val Ser Lys Gly Cys Val Ala Ala Pro 
            20                  25                  30          
Asn Ala Ile Leu Glu Val His Val Leu Pro Leu Glu Phe Pro Thr Gly 
        35                  40                  45              
Pro Ser Gln Leu Glu Leu Thr Leu Gln Ala Ser Lys Gln Asn Gly Thr 
    50                  55                  60                  
Trp Pro Arg Glu Val Leu Leu Val Leu Ser Val Asn Ser Ser Val Phe 
65                  70                  75                  80  
Leu His Leu Gln Ala Leu Gly Ile Pro Leu His Leu Ala Tyr Asn Ser 
                85                  90                  95      
Ser Leu Val Thr Phe Gln Glu Pro Pro Gly Val Asn Thr Thr Glu Leu 
            100                 105                 110         
Pro Ser Phe Pro Lys Thr Gln Ile Leu Glu Trp Ala Ala Glu Arg Gly 
        115                 120                 125             
Pro Ile Thr Ser Ala Ala Glu Leu Asn Asp Pro Gln Ser Ile Leu Leu 
    130                 135                 140                 
Arg Leu Gly Gln Ala Gln Gly Ser Leu Ser Phe Cys Met Leu Glu Ala 
145                 150                 155                 160 
Ser Gln Asp Met Gly Arg Thr Leu Glu Trp Arg Pro Arg Thr Pro Ala 
                165                 170                 175     
Leu Val Arg Gly Cys His Leu Glu Gly Val Ala Gly His Lys Glu Ala 
            180                 185                 190         
His Ile Leu Arg Val Leu Pro Gly His Ser Ala Gly Pro Arg Thr Val 
        195                 200                 205             
Thr Val Lys Val Glu Leu Ser Cys Ala Pro Gly Asp Leu Asp Ala Val 
    210                 215                 220                 
Leu Ile Leu Gln Gly Pro Pro Tyr Val Ser Trp Leu Ile Asp Ala Asn 
225                 230                 235                 240 
His Asn Met Gln Ile Trp Thr Thr Gly Glu Tyr Ser Phe Lys Ile Phe 
                245                 250                 255     
Pro Glu Lys Asn Ile Arg Gly Phe Lys Leu Pro Asp Thr Pro Gln Gly 
            260                 265                 270         
Leu Leu Gly Glu Ala Arg Met Leu Asn Ala Ser Ile Val Ala Ser Phe 
        275                 280                 285             
Val Glu Leu Pro Leu Ala Ser Ile Val Ser Leu His Ala Ser Ser Cys 
    290                 295                 300                 
Gly Gly Arg Leu Gln Thr Ser Pro Ala Pro Ile Gln Thr Thr Pro Pro 
305                 310                 315                 320 
Lys Asp Thr Cys Ser Pro Glu Leu Leu Met Ser Leu Ile Gln Thr Lys 
                325                 330                 335     
Cys Ala Asp Asp Ala Met Thr Leu Val Leu Lys Lys Glu Leu Val Ala 
            340                 345                 350         
His Leu Lys Cys Thr Ile Thr Gly Leu Thr Phe Trp Asp Pro Ser Cys 
        355                 360                 365             
Glu Ala Glu Asp Arg Gly Asp Lys Phe Val Leu Arg Ser Ala Tyr Ser 
    370                 375                 380                 
Ser Cys Gly Met Gln Val Ser Ala Ser Met Ile Ser Asn Glu Ala Val 
385                 390                 395                 400 
Val Asn Ile Leu Ser Ser Ser Ser Pro Gln Arg Lys Lys Val His Cys 
                405                 410                 415     
Leu Asn Met Asp Ser Leu Ser Phe Gln Leu Gly Leu Tyr Leu Ser Pro 
            420                 425                 430         
His Phe Leu Trp Ala Ser Asn Thr Ile Glu Pro Gly Gln Gln Ser Phe 
        435                 440                 445             
Val Gln Val Arg Val Ser Pro Ser Val Ser Glu Phe Leu Leu Ser Leu 
    450                 455                 460                 
Asp Ser Cys His Leu Asp Leu Gly Pro Glu Gly Gly Thr Val Glu Leu 
465                 470                 475                 480 
Ile Gln Gly Arg Ala Ala Lys Gly Asn Cys Val Ser Leu Leu Ser Pro 
                485                 490                 495     
Ser Pro Glu Gly Asp Pro Arg Phe Ser Phe Leu Leu His Phe Tyr Thr 
            500                 505                 510         
Val Pro Ile Pro Lys Thr Gly Thr Leu Ser Cys Thr Val Ala Leu Arg 
        515                 520                 525             
Pro Lys Thr Gly Ser Gln Asp Gln Glu Val His Arg Thr Val Phe Met 
    530                 535                 540                 
Arg Leu Asn Ile Ile Ser Pro Asp Leu Ser Gly Cys Thr Ser Lys Gly 
545                 550                 555                 560 
Leu Val Leu Pro Ala Val Leu Gly Ile Thr Phe Gly Ala Phe Leu Ile 
                565                 570                 575     
Gly Ala Leu Leu Thr Ala Ala Leu Trp Tyr Ile Tyr Ser His Thr Arg 
            580                 585                 590         
Ser Pro Ser Lys Arg Glu Pro Val Val Ala Val Ala Ala Pro Ala Ser 
        595                 600                 605             
Ser Glu Ser Ser Ser Thr Asn His Ser Ile Gly Ser Thr Gln Ser Thr 
    610                 615                 620                 
Pro Cys Ser Thr Ser Ser Met Ala 
625                 630         

