                         SEQUENCE LISTING

<110>  Cygnal Theraeutics, Inc.
       Piizzi, Grazia
       Eugene, Chekler
       Hurov, Johnathan B
       Lantermann, Alexandra
       Couto, Kiley M
       Xu, Hua
       Sarkar, Sourav
       Lefker, Bruce A
       Robinson, Ralph P
       Kysil, Volodymyr
 
<120>  DEGRADERS OF GRK2 AND USES THEREOF

<130>  V0306.70001WO00

<140>  PCT/US2022/013295
<141>  2022-01-21

<150>  US 63/140,576
<151>  2021-01-22

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  2070
<212>  DNA
<213>  Homo sapiens

<400>  1
atggcggacc tggaggcggt gctggccgac gtgagctacc tgatggccat ggagaagagc       60

aaggccacgc cggccgcgcg cgccagcaag aagatcctgc tgcccgagcc cagcatccgc      120

agtgtcatgc agaagtacct ggaggaccgg ggcgaggtga cctttgagaa gatcttttcc      180

cagaagctgg ggtacctgct cttccgagac ttctgcctga accacctgga ggaggccagg      240

cccttggtgg aattctatga ggagatcaag aagtacgaga agctggagac ggaggaggag      300

cgtgtggccc gcagccggga gatcttcgac tcatacatca tgaaggagct gctggcctgc      360

tcgcatccct tctcgaagag tgccactgag catgtccaag gccacctggg gaagaagcag      420

gtgcctccgg atctcttcca gccatacatc gaagagattt gtcaaaacct ccgaggggac      480

gtgttccaga aattcattga gagcgataag ttcacacggt tttgccagtg gaagaatgtg      540

gagctcaaca tccacctgac catgaatgac ttcagcgtgc atcgcatcat tgggcgcggg      600

ggctttggcg aggtctatgg gtgccggaag gctgacacag gcaagatgta cgccatgaag      660

tgcctggaca aaaagcgcat caagatgaag cagggggaga ccctggccct gaacgagcgc      720

atcatgctct cgctcgtcag cactggggac tgcccattca ttgtctgcat gtcatacgcg      780

ttccacacgc cagacaagct cagcttcatc ctggacctca tgaacggtgg ggacctgcac      840

taccacctct cccagcacgg ggtcttctca gaggctgaca tgcgcttcta tgcggccgag      900

atcatcctgg gcctggagca catgcacaac cgcttcgtgg tctaccggga cctgaagcca      960

gccaacatcc ttctggacga gcatggccac gtgcggatct cggacctggg cctggcctgt     1020

gacttctcca agaagaagcc ccatgccagc gtgggcaccc acgggtacat ggctccggag     1080

gtcctgcaga agggcgtggc ctacgacagc agtgccgact ggttctctct ggggtgcatg     1140

ctcttcaagt tgctgcgggg gcacagcccc ttccggcagc acaagaccaa agacaagcat     1200

gagatcgacc gcatgacgct gacgatggcc gtggagctgc ccgactcctt ctcccctgaa     1260

ctacgctccc tgctggaggg gttgctgcag agggatgtca accggagatt gggctgcctg     1320

ggccgagggg ctcaggaggt gaaagagagc ccctttttcc gctccctgga ctggcagatg     1380

gtcttcttgc agaagtaccc tcccccgctg atccccccac gaggggaggt gaacgcggcc     1440

gacgccttcg acattggctc cttcgatgag gaggacacaa aaggaatcaa gttactggac     1500

agtgatcagg agctctaccg caacttcccc ctcaccatct cggagcggtg gcagcaggag     1560

gtggcagaga ctgtcttcga caccatcaac gctgagacag accggctgga ggctcgcaag     1620

aaagccaaga acaagcagct gggccatgag gaagactacg ccctgggcaa ggactgcatc     1680

atgcatggct acatgtccaa gatgggcaac cccttcctga cccagtggca gcggcggtac     1740

ttctacctgt tccccaaccg cctcgagtgg cggggcgagg gcgaggcccc gcagagcctg     1800

ctgaccatgg aggagatcca gtcggtggag gagacgcaga tcaaggagcg caagtgcctg     1860

ctcctcaaga tccgcggtgg gaaacagttc attttgcagt gcgatagcga ccctgagctg     1920

gtgcagtgga agaaggagct gcgcgacgcc taccgcgagg cccagcagct ggtgcagcgg     1980

gtgcccaaga tgaagaacaa gccgcgctcg cccgtggtgg agctgagcaa ggtgccgctg     2040

gtccagcgcg gcagtgccaa cggcctctga                                      2070


<210>  2
<211>  689
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Ala Asp Leu Glu Ala Val Leu Ala Asp Val Ser Tyr Leu Met Ala 
1               5                   10                  15      


Met Glu Lys Ser Lys Ala Thr Pro Ala Ala Arg Ala Ser Lys Lys Ile 
            20                  25                  30          


Leu Leu Pro Glu Pro Ser Ile Arg Ser Val Met Gln Lys Tyr Leu Glu 
        35                  40                  45              


Asp Arg Gly Glu Val Thr Phe Glu Lys Ile Phe Ser Gln Lys Leu Gly 
    50                  55                  60                  


Tyr Leu Leu Phe Arg Asp Phe Cys Leu Asn His Leu Glu Glu Ala Arg 
65                  70                  75                  80  


Pro Leu Val Glu Phe Tyr Glu Glu Ile Lys Lys Tyr Glu Lys Leu Glu 
                85                  90                  95      


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


Ile Met Lys Glu Leu Leu Ala Cys Ser His Pro Phe Ser Lys Ser Ala 
        115                 120                 125             


Thr Glu His Val Gln Gly His Leu Gly Lys Lys Gln Val Pro Pro Asp 
    130                 135                 140                 


Leu Phe Gln Pro Tyr Ile Glu Glu Ile Cys Gln Asn Leu Arg Gly Asp 
145                 150                 155                 160 


Val Phe Gln Lys Phe Ile Glu Ser Asp Lys Phe Thr Arg Phe Cys Gln 
                165                 170                 175     


Trp Lys Asn Val Glu Leu Asn Ile His Leu Thr Met Asn Asp Phe Ser 
            180                 185                 190         


Val His Arg Ile Ile Gly Arg Gly Gly Phe Gly Glu Val Tyr Gly Cys 
        195                 200                 205             


Arg Lys Ala Asp Thr Gly Lys Met Tyr Ala Met Lys Cys Leu Asp Lys 
    210                 215                 220                 


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


Ile Met Leu Ser Leu Val Ser Thr Gly Asp Cys Pro Phe Ile Val Cys 
                245                 250                 255     


Met Ser Tyr Ala Phe His Thr Pro Asp Lys Leu Ser Phe Ile Leu Asp 
            260                 265                 270         


Leu Met Asn Gly Gly Asp Leu His Tyr His Leu Ser Gln His Gly Val 
        275                 280                 285             


Phe Ser Glu Ala Asp Met Arg Phe Tyr Ala Ala Glu Ile Ile Leu Gly 
    290                 295                 300                 


Leu Glu His Met His Asn Arg Phe Val Val Tyr Arg Asp Leu Lys Pro 
305                 310                 315                 320 


Ala Asn Ile Leu Leu Asp Glu His Gly His Val Arg Ile Ser Asp Leu 
                325                 330                 335     


Gly Leu Ala Cys Asp Phe Ser Lys Lys Lys Pro His Ala Ser Val Gly 
            340                 345                 350         


Thr His Gly Tyr Met Ala Pro Glu Val Leu Gln Lys Gly Val Ala Tyr 
        355                 360                 365             


Asp Ser Ser Ala Asp Trp Phe Ser Leu Gly Cys Met Leu Phe Lys Leu 
    370                 375                 380                 


Leu Arg Gly His Ser Pro Phe Arg Gln His Lys Thr Lys Asp Lys His 
385                 390                 395                 400 


Glu Ile Asp Arg Met Thr Leu Thr Met Ala Val Glu Leu Pro Asp Ser 
                405                 410                 415     


Phe Ser Pro Glu Leu Arg Ser Leu Leu Glu Gly Leu Leu Gln Arg Asp 
            420                 425                 430         


Val Asn Arg Arg Leu Gly Cys Leu Gly Arg Gly Ala Gln Glu Val Lys 
        435                 440                 445             


Glu Ser Pro Phe Phe Arg Ser Leu Asp Trp Gln Met Val Phe Leu Gln 
    450                 455                 460                 


Lys Tyr Pro Pro Pro Leu Ile Pro Pro Arg Gly Glu Val Asn Ala Ala 
465                 470                 475                 480 


Asp Ala Phe Asp Ile Gly Ser Phe Asp Glu Glu Asp Thr Lys Gly Ile 
                485                 490                 495     


Lys Leu Leu Asp Ser Asp Gln Glu Leu Tyr Arg Asn Phe Pro Leu Thr 
            500                 505                 510         


Ile Ser Glu Arg Trp Gln Gln Glu Val Ala Glu Thr Val Phe Asp Thr 
        515                 520                 525             


Ile Asn Ala Glu Thr Asp Arg Leu Glu Ala Arg Lys Lys Ala Lys Asn 
    530                 535                 540                 


Lys Gln Leu Gly His Glu Glu Asp Tyr Ala Leu Gly Lys Asp Cys Ile 
545                 550                 555                 560 


Met His Gly Tyr Met Ser Lys Met Gly Asn Pro Phe Leu Thr Gln Trp 
                565                 570                 575     


Gln Arg Arg Tyr Phe Tyr Leu Phe Pro Asn Arg Leu Glu Trp Arg Gly 
            580                 585                 590         


Glu Gly Glu Ala Pro Gln Ser Leu Leu Thr Met Glu Glu Ile Gln Ser 
        595                 600                 605             


Val Glu Glu Thr Gln Ile Lys Glu Arg Lys Cys Leu Leu Leu Lys Ile 
    610                 615                 620                 


Arg Gly Gly Lys Gln Phe Ile Leu Gln Cys Asp Ser Asp Pro Glu Leu 
625                 630                 635                 640 


Val Gln Trp Lys Lys Glu Leu Arg Asp Ala Tyr Arg Glu Ala Gln Gln 
                645                 650                 655     


Leu Val Gln Arg Val Pro Lys Met Lys Asn Lys Pro Arg Ser Pro Val 
            660                 665                 670         


Val Glu Leu Ser Lys Val Pro Leu Val Gln Arg Gly Ser Ala Asn Gly 
        675                 680                 685             


Leu 
    


<210>  3
<211>  688
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Ala Asp Leu Glu Ala Val Leu Ala Asp Val Ser Tyr Leu Met Ala 
1               5                   10                  15      


Met Glu Lys Ser Lys Ala Thr Pro Ala Ala Arg Ala Ser Lys Arg Ile 
            20                  25                  30          


Val Leu Pro Glu Pro Ser Ile Arg Ser Val Met Gln Lys Tyr Leu Ala 
        35                  40                  45              


Glu Arg Asn Glu Ile Thr Phe Asp Lys Ile Phe Asn Gln Lys Ile Gly 
    50                  55                  60                  


Phe Leu Leu Phe Lys Asp Phe Cys Leu Asn Glu Ile Asn Glu Ala Val 
65                  70                  75                  80  


Pro Gln Val Lys Phe Tyr Glu Glu Ile Lys Glu Tyr Glu Lys Leu Asp 
                85                  90                  95      


Asn Glu Glu Asp Arg Leu Cys Arg Ser Arg Gln Ile Tyr Asp Ala Tyr 
            100                 105                 110         


Ile Met Lys Glu Leu Leu Ser Cys Ser His Pro Phe Ser Lys Gln Ala 
        115                 120                 125             


Val Glu His Val Gln Ser His Leu Ser Lys Lys Gln Val Thr Ser Thr 
    130                 135                 140                 


Leu Phe Gln Pro Tyr Ile Glu Glu Ile Cys Glu Ser Leu Arg Gly Asp 
145                 150                 155                 160 


Ile Phe Gln Lys Phe Met Glu Ser Asp Lys Phe Thr Arg Phe Cys Gln 
                165                 170                 175     


Trp Lys Asn Val Glu Leu Asn Ile His Leu Thr Met Asn Glu Phe Ser 
            180                 185                 190         


Val His Arg Ile Ile Gly Arg Gly Gly Phe Gly Glu Val Tyr Gly Cys 
        195                 200                 205             


Arg Lys Ala Asp Thr Gly Lys Met Tyr Ala Met Lys Cys Leu Asp Lys 
    210                 215                 220                 


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


Ile Met Leu Ser Leu Val Ser Thr Gly Asp Cys Pro Phe Ile Val Cys 
                245                 250                 255     


Met Thr Tyr Ala Phe His Thr Pro Asp Lys Leu Cys Phe Ile Leu Asp 
            260                 265                 270         


Leu Met Asn Gly Gly Asp Leu His Tyr His Leu Ser Gln His Gly Val 
        275                 280                 285             


Phe Ser Glu Lys Glu Met Arg Phe Tyr Ala Thr Glu Ile Ile Leu Gly 
    290                 295                 300                 


Leu Glu His Met His Asn Arg Phe Val Val Tyr Arg Asp Leu Lys Pro 
305                 310                 315                 320 


Ala Asn Ile Leu Leu Asp Glu His Gly His Ala Arg Ile Ser Asp Leu 
                325                 330                 335     


Gly Leu Ala Cys Asp Phe Ser Lys Lys Lys Pro His Ala Ser Val Gly 
            340                 345                 350         


Thr His Gly Tyr Met Ala Pro Glu Val Leu Gln Lys Gly Thr Ala Tyr 
        355                 360                 365             


Asp Ser Ser Ala Asp Trp Phe Ser Leu Gly Cys Met Leu Phe Lys Leu 
    370                 375                 380                 


Leu Arg Gly His Ser Pro Phe Arg Gln His Lys Thr Lys Asp Lys His 
385                 390                 395                 400 


Glu Ile Asp Arg Met Thr Leu Thr Val Asn Val Glu Leu Pro Asp Thr 
                405                 410                 415     


Phe Ser Pro Glu Leu Lys Ser Leu Leu Glu Gly Leu Leu Gln Arg Asp 
            420                 425                 430         


Val Ser Lys Arg Leu Gly Cys His Gly Gly Gly Ser Gln Glu Val Lys 
        435                 440                 445             


Glu His Ser Phe Phe Lys Gly Val Asp Trp Gln His Val Tyr Leu Gln 
    450                 455                 460                 


Lys Tyr Pro Pro Pro Leu Ile Pro Pro Arg Gly Glu Val Asn Ala Ala 
465                 470                 475                 480 


Asp Ala Phe Asp Ile Gly Ser Phe Asp Glu Glu Asp Thr Lys Gly Ile 
                485                 490                 495     


Lys Leu Leu Asp Cys Asp Gln Glu Leu Tyr Lys Asn Phe Pro Leu Val 
            500                 505                 510         


Ile Ser Glu Arg Trp Gln Gln Glu Val Thr Glu Thr Val Tyr Glu Ala 
        515                 520                 525             


Val Asn Ala Asp Thr Asp Lys Ile Glu Ala Arg Lys Arg Ala Lys Asn 
    530                 535                 540                 


Lys Gln Leu Gly His Glu Glu Asp Tyr Ala Leu Gly Lys Asp Cys Ile 
545                 550                 555                 560 


Met His Gly Tyr Met Leu Lys Leu Gly Asn Pro Phe Leu Thr Gln Trp 
                565                 570                 575     


Gln Arg Arg Tyr Phe Tyr Leu Phe Pro Asn Arg Leu Glu Trp Arg Gly 
            580                 585                 590         


Glu Gly Glu Ser Arg Gln Asn Leu Leu Thr Met Glu Gln Ile Leu Ser 
        595                 600                 605             


Val Glu Glu Thr Gln Ile Lys Asp Lys Lys Cys Ile Leu Phe Arg Ile 
    610                 615                 620                 


Lys Gly Gly Lys Gln Phe Val Leu Gln Cys Glu Ser Asp Pro Glu Phe 
625                 630                 635                 640 


Val Gln Trp Lys Lys Glu Leu Asn Glu Thr Phe Lys Glu Ala Gln Arg 
                645                 650                 655     


Leu Leu Arg Arg Ala Pro Lys Phe Leu Asn Lys Pro Arg Ser Gly Thr 
            660                 665                 670         


Val Glu Leu Pro Lys Pro Ser Leu Cys His Arg Asn Ser Asn Gly Leu 
        675                 680                 685             


