                         SEQUENCE LISTING

<110>  Epizyme, Inc.
       
<120>  PRMT5 INHIBITORS AND USES THEREOF

<130>  E0501.70018WO00

<140>  Not Yet Assigned
<141>  2015-06-25

<150>  US 62/064,357
<151>  2014-10-15

<150>  US 62/051,751
<151>  2014-09-17

<150>  US 62/017,055
<151>  2014-06-25

<160>  7     

<170>  PatentIn version 3.5

<210>  1
<211>  637
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ala Ala Met Ala Val Gly Gly Ala Gly Gly Ser Arg Val Ser Ser 
1               5                   10                  15      


Gly Arg Asp Leu Asn Cys Val Pro Glu Ile Ala Asp Thr Leu Gly Ala 
            20                  25                  30          


Val Ala Lys Gln Gly Phe Asp Phe Leu Cys Met Pro Val Phe His Pro 
        35                  40                  45              


Arg Phe Lys Arg Glu Phe Ile Gln Glu Pro Ala Lys Asn Arg Pro Gly 
    50                  55                  60                  


Pro Gln Thr Arg Ser Asp Leu Leu Leu Ser Gly Arg Asp Trp Asn Thr 
65                  70                  75                  80  


Leu Ile Val Gly Lys Leu Ser Pro Trp Ile Arg Pro Asp Ser Lys Val 
                85                  90                  95      


Glu Lys Ile Arg Arg Asn Ser Glu Ala Ala Met Leu Gln Glu Leu Asn 
            100                 105                 110         


Phe Gly Ala Tyr Leu Gly Leu Pro Ala Phe Leu Leu Pro Leu Asn Gln 
        115                 120                 125             


Glu Asp Asn Thr Asn Leu Ala Arg Val Leu Thr Asn His Ile His Thr 
    130                 135                 140                 


Gly His His Ser Ser Met Phe Trp Met Arg Val Pro Leu Val Ala Pro 
145                 150                 155                 160 


Glu Asp Leu Arg Asp Asp Ile Ile Glu Asn Ala Pro Thr Thr His Thr 
                165                 170                 175     


Glu Glu Tyr Ser Gly Glu Glu Lys Thr Trp Met Trp Trp His Asn Phe 
            180                 185                 190         


Arg Thr Leu Cys Asp Tyr Ser Lys Arg Ile Ala Val Ala Leu Glu Ile 
        195                 200                 205             


Gly Ala Asp Leu Pro Ser Asn His Val Ile Asp Arg Trp Leu Gly Glu 
    210                 215                 220                 


Pro Ile Lys Ala Ala Ile Leu Pro Thr Ser Ile Phe Leu Thr Asn Lys 
225                 230                 235                 240 


Lys Gly Phe Pro Val Leu Ser Lys Met His Gln Arg Leu Ile Phe Arg 
                245                 250                 255     


Leu Leu Lys Leu Glu Val Gln Phe Ile Ile Thr Gly Thr Asn His His 
            260                 265                 270         


Ser Glu Lys Glu Phe Cys Ser Tyr Leu Gln Tyr Leu Glu Tyr Leu Ser 
        275                 280                 285             


Gln Asn Arg Pro Pro Pro Asn Ala Tyr Glu Leu Phe Ala Lys Gly Tyr 
    290                 295                 300                 


Glu Asp Tyr Leu Gln Ser Pro Leu Gln Pro Leu Met Asp Asn Leu Glu 
305                 310                 315                 320 


Ser Gln Thr Tyr Glu Val Phe Glu Lys Asp Pro Ile Lys Tyr Ser Gln 
                325                 330                 335     


Tyr Gln Gln Ala Ile Tyr Lys Cys Leu Leu Asp Arg Val Pro Glu Glu 
            340                 345                 350         


Glu Lys Asp Thr Asn Val Gln Val Leu Met Val Leu Gly Ala Gly Arg 
        355                 360                 365             


Gly Pro Leu Val Asn Ala Ser Leu Arg Ala Ala Lys Gln Ala Asp Arg 
    370                 375                 380                 


Arg Ile Lys Leu Tyr Ala Val Glu Lys Asn Pro Asn Ala Val Val Thr 
385                 390                 395                 400 


Leu Glu Asn Trp Gln Phe Glu Glu Trp Gly Ser Gln Val Thr Val Val 
                405                 410                 415     


Ser Ser Asp Met Arg Glu Trp Val Ala Pro Glu Lys Ala Asp Ile Ile 
            420                 425                 430         


Val Ser Glu Leu Leu Gly Ser Phe Ala Asp Asn Glu Leu Ser Pro Glu 
        435                 440                 445             


Cys Leu Asp Gly Ala Gln His Phe Leu Lys Asp Asp Gly Val Ser Ile 
    450                 455                 460                 


Pro Gly Glu Tyr Thr Ser Phe Leu Ala Pro Ile Ser Ser Ser Lys Leu 
465                 470                 475                 480 


Tyr Asn Glu Val Arg Ala Cys Arg Glu Lys Asp Arg Asp Pro Glu Ala 
                485                 490                 495     


Gln Phe Glu Met Pro Tyr Val Val Arg Leu His Asn Phe His Gln Leu 
            500                 505                 510         


Ser Ala Pro Gln Pro Cys Phe Thr Phe Ser His Pro Asn Arg Asp Pro 
        515                 520                 525             


Met Ile Asp Asn Asn Arg Tyr Cys Thr Leu Glu Phe Pro Val Glu Val 
    530                 535                 540                 


Asn Thr Val Leu His Gly Phe Ala Gly Tyr Phe Glu Thr Val Leu Tyr 
545                 550                 555                 560 


Gln Asp Ile Thr Leu Ser Ile Arg Pro Glu Thr His Ser Pro Gly Met 
                565                 570                 575     


Phe Ser Trp Phe Pro Ile Leu Phe Pro Ile Lys Gln Pro Ile Thr Val 
            580                 585                 590         


Arg Glu Gly Gln Thr Ile Cys Val Arg Phe Trp Arg Cys Ser Asn Ser 
        595                 600                 605             


Lys Lys Val Trp Tyr Glu Trp Ala Val Thr Ala Pro Val Cys Ser Ala 
    610                 615                 620                 


Ile His Asn Pro Thr Gly Arg Ser Tyr Thr Ile Gly Leu 
625                 630                 635         


<210>  2
<211>  620
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Arg Gly Pro Asn Ser Gly Thr Glu Lys Gly Arg Leu Val Ile Pro 
1               5                   10                  15      


Glu Lys Gln Gly Phe Asp Phe Leu Cys Met Pro Val Phe His Pro Arg 
            20                  25                  30          


Phe Lys Arg Glu Phe Ile Gln Glu Pro Ala Lys Asn Arg Pro Gly Pro 
        35                  40                  45              


Gln Thr Arg Ser Asp Leu Leu Leu Ser Gly Arg Asp Trp Asn Thr Leu 
    50                  55                  60                  


Ile Val Gly Lys Leu Ser Pro Trp Ile Arg Pro Asp Ser Lys Val Glu 
65                  70                  75                  80  


Lys Ile Arg Arg Asn Ser Glu Ala Ala Met Leu Gln Glu Leu Asn Phe 
                85                  90                  95      


Gly Ala Tyr Leu Gly Leu Pro Ala Phe Leu Leu Pro Leu Asn Gln Glu 
            100                 105                 110         


Asp Asn Thr Asn Leu Ala Arg Val Leu Thr Asn His Ile His Thr Gly 
        115                 120                 125             


His His Ser Ser Met Phe Trp Met Arg Val Pro Leu Val Ala Pro Glu 
    130                 135                 140                 


Asp Leu Arg Asp Asp Ile Ile Glu Asn Ala Pro Thr Thr His Thr Glu 
145                 150                 155                 160 


Glu Tyr Ser Gly Glu Glu Lys Thr Trp Met Trp Trp His Asn Phe Arg 
                165                 170                 175     


Thr Leu Cys Asp Tyr Ser Lys Arg Ile Ala Val Ala Leu Glu Ile Gly 
            180                 185                 190         


Ala Asp Leu Pro Ser Asn His Val Ile Asp Arg Trp Leu Gly Glu Pro 
        195                 200                 205             


Ile Lys Ala Ala Ile Leu Pro Thr Ser Ile Phe Leu Thr Asn Lys Lys 
    210                 215                 220                 


Gly Phe Pro Val Leu Ser Lys Met His Gln Arg Leu Ile Phe Arg Leu 
225                 230                 235                 240 


Leu Lys Leu Glu Val Gln Phe Ile Ile Thr Gly Thr Asn His His Ser 
                245                 250                 255     


Glu Lys Glu Phe Cys Ser Tyr Leu Gln Tyr Leu Glu Tyr Leu Ser Gln 
            260                 265                 270         


Asn Arg Pro Pro Pro Asn Ala Tyr Glu Leu Phe Ala Lys Gly Tyr Glu 
        275                 280                 285             


Asp Tyr Leu Gln Ser Pro Leu Gln Pro Leu Met Asp Asn Leu Glu Ser 
    290                 295                 300                 


Gln Thr Tyr Glu Val Phe Glu Lys Asp Pro Ile Lys Tyr Ser Gln Tyr 
305                 310                 315                 320 


Gln Gln Ala Ile Tyr Lys Cys Leu Leu Asp Arg Val Pro Glu Glu Glu 
                325                 330                 335     


Lys Asp Thr Asn Val Gln Val Leu Met Val Leu Gly Ala Gly Arg Gly 
            340                 345                 350         


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


Ile Lys Leu Tyr Ala Val Glu Lys Asn Pro Asn Ala Val Val Thr Leu 
    370                 375                 380                 


Glu Asn Trp Gln Phe Glu Glu Trp Gly Ser Gln Val Thr Val Val Ser 
385                 390                 395                 400 


Ser Asp Met Arg Glu Trp Val Ala Pro Glu Lys Ala Asp Ile Ile Val 
                405                 410                 415     


Ser Glu Leu Leu Gly Ser Phe Ala Asp Asn Glu Leu Ser Pro Glu Cys 
            420                 425                 430         


Leu Asp Gly Ala Gln His Phe Leu Lys Asp Asp Gly Val Ser Ile Pro 
        435                 440                 445             


Gly Glu Tyr Thr Ser Phe Leu Ala Pro Ile Ser Ser Ser Lys Leu Tyr 
    450                 455                 460                 


Asn Glu Val Arg Ala Cys Arg Glu Lys Asp Arg Asp Pro Glu Ala Gln 
465                 470                 475                 480 


Phe Glu Met Pro Tyr Val Val Arg Leu His Asn Phe His Gln Leu Ser 
                485                 490                 495     


Ala Pro Gln Pro Cys Phe Thr Phe Ser His Pro Asn Arg Asp Pro Met 
            500                 505                 510         


Ile Asp Asn Asn Arg Tyr Cys Thr Leu Glu Phe Pro Val Glu Val Asn 
        515                 520                 525             


Thr Val Leu His Gly Phe Ala Gly Tyr Phe Glu Thr Val Leu Tyr Gln 
    530                 535                 540                 


Asp Ile Thr Leu Ser Ile Arg Pro Glu Thr His Ser Pro Gly Met Phe 
545                 550                 555                 560 


Ser Trp Phe Pro Ile Leu Phe Pro Ile Lys Gln Pro Ile Thr Val Arg 
                565                 570                 575     


Glu Gly Gln Thr Ile Cys Val Arg Phe Trp Arg Cys Ser Asn Ser Lys 
            580                 585                 590         


Lys Val Trp Tyr Glu Trp Ala Val Thr Ala Pro Val Cys Ser Ala Ile 
        595                 600                 605             


His Asn Pro Thr Gly Arg Ser Tyr Thr Ile Gly Leu 
    610                 615                 620 


<210>  3
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide

<400>  3

Ser Gly Arg Gly Lys Gly Gly Lys Gly Leu Gly Lys Gly Gly Ala Lys 
1               5                   10                  15      


<210>  4
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide

<400>  4

Met Asp Tyr Lys Asp Asp Asp Asp Lys 
1               5                   


<210>  5
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide

<400>  5

Met His His His His His His 
1               5           


<210>  6
<211>  645
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide

<400>  6

Met Asp Tyr Lys Asp Asp Asp Asp Lys Ala Ala Met Ala Val Gly Gly 
1               5                   10                  15      


Ala Gly Gly Ser Arg Val Ser Ser Gly Arg Asp Leu Asn Cys Val Pro 
            20                  25                  30          


Glu Ile Ala Asp Thr Leu Gly Ala Val Ala Lys Gln Gly Phe Asp Phe 
        35                  40                  45              


Leu Cys Met Pro Val Phe His Pro Arg Phe Lys Arg Glu Phe Ile Gln 
    50                  55                  60                  


Glu Pro Ala Lys Asn Arg Pro Gly Pro Gln Thr Arg Ser Asp Leu Leu 
65                  70                  75                  80  


Leu Ser Gly Arg Asp Trp Asn Thr Leu Ile Val Gly Lys Leu Ser Pro 
                85                  90                  95      


Trp Ile Arg Pro Asp Ser Lys Val Glu Lys Ile Arg Arg Asn Ser Glu 
            100                 105                 110         


Ala Ala Met Leu Gln Glu Leu Asn Phe Gly Ala Tyr Leu Gly Leu Pro 
        115                 120                 125             


Ala Phe Leu Leu Pro Leu Asn Gln Glu Asp Asn Thr Asn Leu Ala Arg 
    130                 135                 140                 


Val Leu Thr Asn His Ile His Thr Gly His His Ser Ser Met Phe Trp 
145                 150                 155                 160 


Met Arg Val Pro Leu Val Ala Pro Glu Asp Leu Arg Asp Asp Ile Ile 
                165                 170                 175     


Glu Asn Ala Pro Thr Thr His Thr Glu Glu Tyr Ser Gly Glu Glu Lys 
            180                 185                 190         


Thr Trp Met Trp Trp His Asn Phe Arg Thr Leu Cys Asp Tyr Ser Lys 
        195                 200                 205             


Arg Ile Ala Val Ala Leu Glu Ile Gly Ala Asp Leu Pro Ser Asn His 
    210                 215                 220                 


Val Ile Asp Arg Trp Leu Gly Glu Pro Ile Lys Ala Ala Ile Leu Pro 
225                 230                 235                 240 


Thr Ser Ile Phe Leu Thr Asn Lys Lys Gly Phe Pro Val Leu Ser Lys 
                245                 250                 255     


Met His Gln Arg Leu Ile Phe Arg Leu Leu Lys Leu Glu Val Gln Phe 
            260                 265                 270         


Ile Ile Thr Gly Thr Asn His His Ser Glu Lys Glu Phe Cys Ser Tyr 
        275                 280                 285             


Leu Gln Tyr Leu Glu Tyr Leu Ser Gln Asn Arg Pro Pro Pro Asn Ala 
    290                 295                 300                 


Tyr Glu Leu Phe Ala Lys Gly Tyr Glu Asp Tyr Leu Gln Ser Pro Leu 
305                 310                 315                 320 


Gln Pro Leu Met Asp Asn Leu Glu Ser Gln Thr Tyr Glu Val Phe Glu 
                325                 330                 335     


Lys Asp Pro Ile Lys Tyr Ser Gln Tyr Gln Gln Ala Ile Tyr Lys Cys 
            340                 345                 350         


Leu Leu Asp Arg Val Pro Glu Glu Glu Lys Asp Thr Asn Val Gln Val 
        355                 360                 365             


Leu Met Val Leu Gly Ala Gly Arg Gly Pro Leu Val Asn Ala Ser Leu 
    370                 375                 380                 


Arg Ala Ala Lys Gln Ala Asp Arg Arg Ile Lys Leu Tyr Ala Val Glu 
385                 390                 395                 400 


Lys Asn Pro Asn Ala Val Val Thr Leu Glu Asn Trp Gln Phe Glu Glu 
                405                 410                 415     


Trp Gly Ser Gln Val Thr Val Val Ser Ser Asp Met Arg Glu Trp Val 
            420                 425                 430         


Ala Pro Glu Lys Ala Asp Ile Ile Val Ser Glu Leu Leu Gly Ser Phe 
        435                 440                 445             


Ala Asp Asn Glu Leu Ser Pro Glu Cys Leu Asp Gly Ala Gln His Phe 
    450                 455                 460                 


Leu Lys Asp Asp Gly Val Ser Ile Pro Gly Glu Tyr Thr Ser Phe Leu 
465                 470                 475                 480 


Ala Pro Ile Ser Ser Ser Lys Leu Tyr Asn Glu Val Arg Ala Cys Arg 
                485                 490                 495     


Glu Lys Asp Arg Asp Pro Glu Ala Gln Phe Glu Met Pro Tyr Val Val 
            500                 505                 510         


Arg Leu His Asn Phe His Gln Leu Ser Ala Pro Gln Pro Cys Phe Thr 
        515                 520                 525             


Phe Ser His Pro Asn Arg Asp Pro Met Ile Asp Asn Asn Arg Tyr Cys 
    530                 535                 540                 


Thr Leu Glu Phe Pro Val Glu Val Asn Thr Val Leu His Gly Phe Ala 
545                 550                 555                 560 


Gly Tyr Phe Glu Thr Val Leu Tyr Gln Asp Ile Thr Leu Ser Ile Arg 
                565                 570                 575     


Pro Glu Thr His Ser Pro Gly Met Phe Ser Trp Phe Pro Ile Leu Phe 
            580                 585                 590         


Pro Ile Lys Gln Pro Ile Thr Val Arg Glu Gly Gln Thr Ile Cys Val 
        595                 600                 605             


Arg Phe Trp Arg Cys Ser Asn Ser Lys Lys Val Trp Tyr Glu Trp Ala 
    610                 615                 620                 


Val Thr Ala Pro Val Cys Ser Ala Ile His Asn Pro Thr Gly Arg Ser 
625                 630                 635                 640 


Tyr Thr Ile Gly Leu 
                645 


<210>  7
<211>  348
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Polypeptide

<400>  7

Met His His His His His His Arg Lys Glu Thr Pro Pro Pro Leu Val 
1               5                   10                  15      


Pro Pro Ala Ala Arg Glu Trp Asn Leu Pro Pro Asn Ala Pro Ala Cys 
            20                  25                  30          


Met Glu Arg Gln Leu Glu Ala Ala Arg Tyr Arg Ser Asp Gly Ala Leu 
        35                  40                  45              


Leu Leu Gly Ala Ser Ser Leu Ser Gly Arg Cys Trp Ala Gly Ser Leu 
    50                  55                  60                  


Trp Leu Phe Lys Asp Pro Cys Ala Ala Pro Asn Glu Gly Phe Cys Ser 
65                  70                  75                  80  


Ala Gly Val Gln Thr Glu Ala Gly Val Ala Asp Leu Thr Trp Val Gly 
                85                  90                  95      


Glu Arg Gly Ile Leu Val Ala Ser Asp Ser Gly Ala Val Glu Leu Trp 
            100                 105                 110         


Glu Leu Asp Glu Asn Glu Thr Leu Ile Val Ser Lys Phe Cys Lys Tyr 
        115                 120                 125             


Glu His Asp Asp Ile Val Ser Thr Val Ser Val Leu Ser Ser Gly Thr 
    130                 135                 140                 


Gln Ala Val Ser Gly Ser Lys Asp Ile Cys Ile Lys Val Trp Asp Leu 
145                 150                 155                 160 


Ala Gln Gln Val Val Leu Ser Ser Tyr Arg Ala His Ala Ala Gln Val 
                165                 170                 175     


Thr Cys Val Ala Ala Ser Pro His Lys Asp Ser Val Phe Leu Ser Cys 
            180                 185                 190         


Ser Glu Asp Asn Arg Ile Leu Leu Trp Asp Thr Arg Cys Pro Lys Pro 
        195                 200                 205             


Ala Ser Gln Ile Gly Cys Ser Ala Pro Gly Tyr Leu Pro Thr Ser Leu 
    210                 215                 220                 


Ala Trp His Pro Gln Gln Ser Glu Val Phe Val Phe Gly Asp Glu Asn 
225                 230                 235                 240 


Gly Thr Val Ser Leu Val Asp Thr Lys Ser Thr Ser Cys Val Leu Ser 
                245                 250                 255     


Ser Ala Val His Ser Gln Cys Val Thr Gly Leu Val Phe Ser Pro His 
            260                 265                 270         


Ser Val Pro Phe Leu Ala Ser Leu Ser Glu Asp Cys Ser Leu Ala Val 
        275                 280                 285             


Leu Asp Ser Ser Leu Ser Glu Leu Phe Arg Ser Gln Ala His Arg Asp 
    290                 295                 300                 


Phe Val Arg Asp Ala Thr Trp Ser Pro Leu Asn His Ser Leu Leu Thr 
305                 310                 315                 320 


Thr Val Gly Trp Asp His Gln Val Val His His Val Val Pro Thr Glu 
                325                 330                 335     


Pro Leu Pro Ala Pro Gly Pro Ala Ser Val Thr Glu 
            340                 345             


