                         SEQUENCE LISTING

<110>  THE UNIVERSITY OF WESTERN ONTARIO
       STRONG, Michael et al.
 
<120>  METHODS FOR TREATMENT OF NEURON DEGENERATION

<130>  0118494.0180

<140>  PCT/CA2022/050665
<141>  2022-04-29

<150>  US 63/181,452
<151>  2021-04-29

<160>  16    

<170>  PatentIn version 3.5

<210>  1
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-deltaGEF Forward primer

<400>  1
attggtacca tggagttgag ctgcagcgaa                                        30


<210>  2
<211>  32
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-deltaGEF Reverse primer

<400>  2
taaggaggtg tttgatgaca tccttctcct gc                                     32


<210>  3
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-deltaGEF Forward primer

<400>  3
tgtcatcaaa cacctcctta ttaaacctga ccca                                   34


<210>  4
<211>  32
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-deltaGEF Reverse primer

<400>  4
agactcgagc accttgaggt ctacttgatg tt                                     32


<210>  5
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-deltaRBD Forward primer

<400>  5
attggtacca tggagttgag ctgcagcgaa                                        30


<210>  6
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-deltaRBD Reverse primer

<400>  6
caactggagg ggctctagat ggacgtcctc                                        30


<210>  7
<211>  30
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-NH2 Forward primer

<400>  7
attggtacca tggagttgag ctgcagcgaa                                        30


<210>  8
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-NH2 Reverse primer

<400>  8
tttctcgagt ttgatgacat ccttctcctg cctattac                               38


<210>  9
<211>  36
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-COOH Forward primer

<400>  9
ataggtacca tgagacagga tgtcattttt gagcta                                 36


<210>  10
<211>  32
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-COOH Reverse primer

<400>  10
agactcgagc accttgaggt ctacttgatg tt                                     32


<210>  11
<211>  32
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-NH2-deltaL-rich Forward primer

<400>  11
ataggtacca tgattcactc atcggaaacg ct                                     32


<210>  12
<211>  38
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: RGNEF-NH2-deltaL-rich Reverse primer

<400>  12
tttctcgagt ttgatgacat ccttctcctg cctattac                               38


<210>  13
<211>  1731
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(1731)
<223>  Human RGNEF

<400>  13

Met Glu Leu Ser Cys Ser Glu Ala Pro Leu Tyr Gly Gln Met Met Ile 
1               5                   10                  15      


Tyr Ala Lys Phe Asp Lys Asn Val Tyr Leu Pro Glu Asp Ala Glu Phe 
            20                  25                  30          


Tyr Phe Thr Tyr Asp Gly Ser His Gln Arg His Val Met Ile Ala Glu 
        35                  40                  45              


Arg Ile Glu Asp Asn Val Leu Gln Ser Ser Val Pro Gly His Gly Leu 
    50                  55                  60                  


Gln Glu Thr Val Thr Val Ser Val Cys Leu Cys Ser Glu Gly Tyr Ser 
65                  70                  75                  80  


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


Cys Arg Leu Ala Arg Leu Leu Val Thr Gln Ala Asn Arg Leu Thr Ala 
            100                 105                 110         


Cys Ser His Gln Thr Leu Leu Thr Pro Phe Ala Leu Thr Ala Gly Ala 
        115                 120                 125             


Leu Pro Ala Leu Asp Glu Glu Leu Val Leu Ala Leu Thr His Leu Glu 
    130                 135                 140                 


Leu Pro Leu Glu Trp Thr Val Leu Gly Ser Ser Ser Leu Glu Val Ser 
145                 150                 155                 160 


Ser His Arg Glu Ser Leu Leu His Leu Ala Met Arg Trp Gly Leu Ala 
                165                 170                 175     


Lys Leu Ser Gln Phe Phe Leu Cys Leu Pro Gly Gly Val Gln Ala Leu 
            180                 185                 190         


Ala Leu Pro Asn Glu Glu Gly Ala Thr Pro Leu Asp Leu Ala Leu Arg 
        195                 200                 205             


Glu Gly His Ser Lys Leu Val Glu Asp Val Thr Asn Phe Gln Gly Arg 
    210                 215                 220                 


Trp Ser Pro Ser Phe Ser Arg Val Gln Leu Ser Glu Glu Ala Ser Leu 
225                 230                 235                 240 


His Tyr Ile His Ser Ser Glu Thr Leu Thr Leu Thr Leu Asn His Thr 
                245                 250                 255     


Ala Glu His Leu Leu Glu Ala Asp Ile Lys Leu Phe Arg Lys Tyr Phe 
            260                 265                 270         


Trp Asp Arg Ala Phe Leu Val Lys Ala Phe Glu Gln Glu Ala Arg Pro 
        275                 280                 285             


Glu Glu Arg Thr Ala Met Pro Ser Ser Gly Ala Glu Thr Glu Glu Glu 
    290                 295                 300                 


Ile Lys Asn Ser Val Ser Ser Arg Ser Ala Ala Glu Lys Glu Asp Ile 
305                 310                 315                 320 


Lys Arg Val Lys Ser Leu Val Val Gln His Asn Glu His Glu Asp Gln 
                325                 330                 335     


His Ser Leu Asp Leu Asp Arg Ser Phe Asp Ile Leu Lys Lys Ser Lys 
            340                 345                 350         


Pro Pro Ser Thr Leu Leu Ala Ala Gly Arg Leu Ser Asp Met Leu Asn 
        355                 360                 365             


Gly Gly Asp Glu Val Tyr Ala Asn Cys Met Val Ile Asp Gln Val Gly 
    370                 375                 380                 


Asp Leu Asp Ile Ser Tyr Ile Asn Ile Glu Gly Ile Thr Ala Thr Thr 
385                 390                 395                 400 


Ser Pro Glu Ser Arg Gly Cys Thr Leu Trp Pro Gln Ser Ser Lys His 
                405                 410                 415     


Thr Leu Pro Thr Glu Thr Ser Pro Ser Val Tyr Pro Leu Ser Glu Asn 
            420                 425                 430         


Val Glu Gly Thr Ala His Thr Glu Ala Gln Gln Ser Phe Met Ser Pro 
        435                 440                 445             


Ser Ser Ser Cys Ala Ser Asn Leu Asn Leu Ser Phe Gly Trp His Gly 
    450                 455                 460                 


Phe Glu Lys Glu Gln Ser His Leu Lys Lys Arg Ser Ser Ser Leu Asp 
465                 470                 475                 480 


Ala Leu Asp Ala Asp Ser Glu Gly Glu Gly His Ser Glu Pro Ser His 
                485                 490                 495     


Ile Cys Tyr Thr Pro Gly Ser Gln Ser Ser Ser Arg Thr Gly Ile Pro 
            500                 505                 510         


Ser Gly Asp Glu Leu Asp Ser Phe Glu Thr Asn Thr Glu Pro Asp Phe 
        515                 520                 525             


Asn Ile Ser Arg Ala Glu Ser Leu Pro Leu Ser Ser Asn Leu Gln Ser 
    530                 535                 540                 


Lys Glu Ser Leu Leu Ser Gly Val Arg Ser Arg Ser Tyr Ser Cys Ser 
545                 550                 555                 560 


Ser Pro Lys Ile Ser Leu Gly Lys Thr Arg Leu Val Arg Glu Leu Thr 
                565                 570                 575     


Val Cys Ser Ser Ser Glu Glu Gln Arg Ala Tyr Ser Leu Ser Glu Pro 
            580                 585                 590         


Pro Arg Glu Asn Arg Ile Gln Glu Glu Glu Trp Asp Lys Tyr Ile Ile 
        595                 600                 605             


Pro Ala Lys Ser Glu Ser Glu Lys Tyr Lys Val Ser Arg Thr Phe Ser 
    610                 615                 620                 


Phe Leu Met Asn Arg Met Thr Ser Pro Arg Asn Lys Ser Lys Thr Lys 
625                 630                 635                 640 


Ser Lys Asp Ala Lys Asp Lys Glu Lys Leu Asn Arg His Gln Phe Ala 
                645                 650                 655     


Pro Gly Thr Phe Ser Gly Val Leu Gln Cys Leu Val Cys Asp Lys Thr 
            660                 665                 670         


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


His Lys Gly Cys Lys Asp Ala Ala Pro Ala Cys Thr Lys Lys Phe Gln 
    690                 695                 700                 


Glu Lys Tyr Asn Lys Asn Lys Pro Gln Thr Ile Leu Gly Asn Ser Ser 
705                 710                 715                 720 


Phe Arg Asp Ile Pro Gln Pro Gly Leu Ser Leu His Pro Ser Ser Ser 
                725                 730                 735     


Val Pro Val Gly Leu Pro Thr Gly Arg Arg Glu Thr Val Gly Gln Val 
            740                 745                 750         


His Pro Leu Ser Arg Ser Val Pro Gly Thr Thr Leu Glu Ser Phe Arg 
        755                 760                 765             


Arg Ser Ala Thr Ser Leu Glu Ser Glu Ser Asp His Asn Ser Cys Arg 
    770                 775                 780                 


Ser Arg Ser His Ser Asp Glu Leu Leu Gln Ser Met Gly Ser Ser Pro 
785                 790                 795                 800 


Ser Thr Glu Ser Phe Ile Met Glu Asp Val Val Asp Ser Ser Leu Trp 
                805                 810                 815     


Ser Asp Leu Ser Ser Asp Ala Gln Glu Phe Glu Ala Glu Ser Trp Ser 
            820                 825                 830         


Leu Val Val Asp Pro Ser Phe Cys Asn Arg Gln Glu Lys Asp Val Ile 
        835                 840                 845             


Lys Arg Gln Asp Val Ile Phe Glu Leu Met Gln Thr Glu Met His His 
    850                 855                 860                 


Ile Gln Thr Leu Phe Ile Met Ser Glu Ile Phe Arg Lys Gly Met Lys 
865                 870                 875                 880 


Glu Glu Leu Gln Leu Asp His Ser Thr Val Asp Lys Ile Phe Pro Cys 
                885                 890                 895     


Leu Asp Glu Leu Leu Glu Ile His Arg His Phe Phe Tyr Ser Met Lys 
            900                 905                 910         


Glu Arg Arg Gln Glu Ser Cys Ala Gly Ser Asp Arg Asn Phe Val Ile 
        915                 920                 925             


Asp Arg Ile Gly Asp Ile Leu Val Gln Gln Phe Ser Glu Glu Asn Ala 
    930                 935                 940                 


Ser Lys Met Lys Lys Ile Tyr Gly Glu Phe Cys Cys His His Lys Glu 
945                 950                 955                 960 


Ala Val Asn Leu Phe Lys Glu Leu Gln Gln Asn Lys Lys Phe Gln Asn 
                965                 970                 975     


Phe Ile Lys Leu Arg Asn Ser Asn Leu Leu Ala Arg Arg Arg Gly Ile 
            980                 985                 990         


Pro Glu Cys Ile Leu Leu Val Thr  Gln Arg Ile Thr Lys  Tyr Pro Val 
        995                 1000                 1005             


Leu Val  Glu Arg Ile Leu Gln  Tyr Thr Lys Glu Arg  Thr Glu Glu 
    1010                 1015                 1020             


His Lys  Asp Leu Arg Lys Ala  Leu Cys Leu Ile Lys  Asp Met Ile 
    1025                 1030                 1035             


Ala Thr  Val Asp Leu Lys Val  Asn Glu Tyr Glu Lys  Asn Gln Lys 
    1040                 1045                 1050             


Trp Leu  Glu Ile Leu Asn Lys  Ile Glu Asn Lys Thr  Tyr Thr Lys 
    1055                 1060                 1065             


Leu Lys  Asn Gly His Val Phe  Arg Lys Gln Ala Leu  Met Ser Glu 
    1070                 1075                 1080             


Glu Arg  Thr Leu Leu Tyr Asp  Gly Leu Val Tyr Trp  Lys Thr Ala 
    1085                 1090                 1095             


Thr Gly  Arg Phe Lys Asp Ile  Leu Ala Leu Leu Leu  Thr Asp Val 
    1100                 1105                 1110             


Leu Leu  Phe Leu Gln Glu Lys  Asp Gln Lys Tyr Ile  Phe Ala Ala 
    1115                 1120                 1125             


Val Asp  Gln Lys Pro Ser Val  Ile Ser Leu Gln Lys  Leu Ile Ala 
    1130                 1135                 1140             


Arg Glu  Val Ala Asn Glu Glu  Arg Gly Met Phe Leu  Ile Ser Ala 
    1145                 1150                 1155             


Ser Ser  Ala Gly Pro Glu Met  Tyr Glu Ile His Thr  Asn Ser Lys 
    1160                 1165                 1170             


Glu Glu  Arg Asn Asn Trp Met  Arg Arg Ile Gln Gln  Ala Val Glu 
    1175                 1180                 1185             


Ser Cys  Pro Glu Glu Lys Gly  Gly Arg Thr Ser Glu  Ser Asp Glu 
    1190                 1195                 1200             


Asp Lys  Arg Lys Ala Glu Ala  Arg Val Ala Lys Ile  Gln Gln Cys 
    1205                 1210                 1215             


Gln Glu  Ile Leu Thr Asn Gln  Asp Gln Gln Ile Cys  Ala Tyr Leu 
    1220                 1225                 1230             


Glu Glu  Lys Leu His Ile Tyr  Ala Glu Leu Gly Glu  Leu Ser Gly 
    1235                 1240                 1245             


Phe Glu  Asp Val His Leu Glu  Pro His Leu Leu Ile  Lys Pro Asp 
    1250                 1255                 1260             


Pro Gly  Glu Pro Pro Gln Ala  Ala Ser Leu Leu Ala  Ala Ala Leu 
    1265                 1270                 1275             


Lys Glu  Ala Glu Ser Leu Gln  Val Ala Val Lys Ala  Ser Gln Met 
    1280                 1285                 1290             


Gly Ala  Val Ser Gln Ser Cys  Glu Asp Ser Cys Gly  Asp Ser Val 
    1295                 1300                 1305             


Leu Ala  Asp Thr Leu Ser Ser  His Asp Val Pro Gly  Ser Pro Thr 
    1310                 1315                 1320             


Ala Ser  Leu Val Thr Gly Gly  Arg Glu Gly Arg Gly  Cys Ser Asp 
    1325                 1330                 1335             


Val Asp  Pro Gly Ile Gln Gly  Val Val Thr Asp Leu  Ala Val Ser 
    1340                 1345                 1350             


Asp Ala  Gly Glu Lys Val Glu  Cys Arg Asn Phe Pro  Gly Ser Ser 
    1355                 1360                 1365             


Gln Ser  Glu Ile Ile Gln Ala  Ile Gln Asn Leu Thr  Arg Leu Leu 
    1370                 1375                 1380             


Tyr Ser  Leu Gln Ala Ala Leu  Thr Ile Gln Asp Ser  His Ile Glu 
    1385                 1390                 1395             


Ile His  Arg Leu Val Leu Gln  Gln Gln Glu Gly Leu  Ser Leu Gly 
    1400                 1405                 1410             


His Ser  Ile Leu Arg Gly Gly  Pro Leu Gln Asp Gln  Lys Ser Arg 
    1415                 1420                 1425             


Asp Ala  Asp Arg Gln His Glu  Glu Leu Ala Asn Val  His Gln Leu 
    1430                 1435                 1440             


Gln His  Gln Leu Gln Gln Glu  Gln Arg Arg Trp Leu  Arg Arg Cys 
    1445                 1450                 1455             


Glu Gln  Gln Gln Arg Ala Gln  Ala Thr Arg Glu Ser  Trp Leu Gln 
    1460                 1465                 1470             


Glu Arg  Glu Arg Glu Cys Gln  Ser Gln Glu Glu Leu  Leu Leu Arg 
    1475                 1480                 1485             


Ser Arg  Gly Glu Leu Asp Leu  Gln Leu Gln Glu Tyr  Gln His Ser 
    1490                 1495                 1500             


Leu Glu  Arg Leu Arg Glu Gly  Gln Arg Leu Val Glu  Arg Glu Gln 
    1505                 1510                 1515             


Ala Arg  Met Arg Ala Gln Gln  Ser Leu Leu Gly His  Trp Lys His 
    1520                 1525                 1530             


Gly Arg  Gln Arg Ser Leu Pro  Ala Val Leu Leu Pro  Gly Gly Pro 
    1535                 1540                 1545             


Glu Val  Met Glu Leu Asn Arg  Ser Glu Ser Leu Cys  His Glu Asn 
    1550                 1555                 1560             


Ser Phe  Phe Ile Asn Glu Ala  Leu Val Gln Met Ser  Phe Asn Thr 
    1565                 1570                 1575             


Phe Asn  Lys Leu Asn Pro Ser  Val Ile His Gln Asp  Ala Thr Tyr 
    1580                 1585                 1590             


Pro Thr  Thr Gln Ser His Ser  Asp Leu Val Arg Thr  Ser Glu His 
    1595                 1600                 1605             


Gln Val  Asp Leu Lys Val Asp  Pro Ser Gln Pro Ser  Asn Val Ser 
    1610                 1615                 1620             


His Lys  Leu Trp Thr Ala Ala  Gly Ser Gly His Gln  Ile Leu Pro 
    1625                 1630                 1635             


Phe His  Glu Ser Ser Lys Asp  Ser Cys Lys Asn Gly  Ser Ser Met 
    1640                 1645                 1650             


Thr Lys  Cys Ser Cys Thr Leu  Thr Ser Pro Pro Gly  Leu Trp Thr 
    1655                 1660                 1665             


Gly Thr  Thr Ser Thr Leu Lys  Asp Leu Asp Thr Ser  His Thr Glu 
    1670                 1675                 1680             


Ser Pro  Thr Pro His Asp Ser  Asn Ser His Arg Pro  Gln Leu Gln 
    1685                 1690                 1695             


Ala Phe  Ile Thr Glu Ala Lys  Leu Asn Leu Pro Thr  Arg Thr Met 
    1700                 1705                 1710             


Thr Arg  Gln Asp Gly Glu Thr  Gly Asp Gly Ala Lys  Glu Asn Ile 
    1715                 1720                 1725             


Val Tyr  Leu 
    1730     


<210>  14
<211>  119
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(119)
<223>  PH Domain

<400>  14

Glu Glu Arg Thr Leu Leu Tyr Asp Gly Leu Val Tyr Trp Lys Thr Ala 
1               5                   10                  15      


Thr Gly Arg Phe Lys Asp Ile Leu Ala Leu Leu Leu Thr Asp Val Leu 
            20                  25                  30          


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


Gln Lys Pro Ser Val Ile Ser Leu Gln Lys Leu Ile Ala Arg Glu Val 
    50                  55                  60                  


Ala Asn Glu Glu Arg Gly Met Phe Leu Ile Ser Ala Ser Ser Ala Gly 
65                  70                  75                  80  


Pro Glu Met Tyr Glu Ile His Thr Asn Ser Lys Glu Glu Arg Asn Asn 
                85                  90                  95      


Trp Met Arg Arg Ile Gln Gln Ala Val Glu Ser Cys Pro Glu Glu Lys 
            100                 105                 110         


Gly Gly Arg Thr Ser Glu Ser 
        115                 


<210>  15
<211>  726
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(726)
<223>  Region of RGNEF that contains the Leu-rich domain

<400>  15
atggagttga gctgcagcga agcacctctt tacgggcaga tgatgatcta tgcgaagttt       60

gacaaaaatg tgtatcttcc tgaagatgct gagttttact ttacttatga cggatctcat      120

cagcgacatg tcatgattgc agagcgcatc gaggataacg ttctccagtc cagcgtccca      180

ggccatgggc ttcaggagac ggtgacggta tctgtgtgcc tctgctcgga aggttactct      240

ccggtgacca tgggctctgg ctcagtgacc tacgtggaca acatggcttg caggctggct      300

cgtctgctgg tgacgcaggc caatcgcctc acagcctgca gccaccagac cctgctgacc      360

ccatttgcct tgacggcagg agcactgcct gccttggatg aggagctcgt gctggctctg      420

acccatctgg aattgcctct agagtggact gtgttgggaa gttcttcact tgaagtatct      480

tctcacagag aatctcttct acacctggct atgagatggg gcctggctaa actttcccag      540

ttcttcttgt gtctcccggg gggagtccag gccttggctt tacccaacga agagggtgcc      600

acaccattag acttagcttt acgtgaagga cactccaagc tggtggaaga cgtcacaaat      660

tttcagggca gatggtcccc aagcttctcc cgagtgcagc tcagtgaaga agcctccttg      720

cattac                                                                 726


<210>  16
<211>  242
<212>  PRT
<213>  Homo sapiens


<220>
<221>  misc_feature
<222>  (1)..(242)
<223>  Region of RGNEF that contains the Leu-rich domain

<400>  16

Met Glu Leu Ser Cys Ser Glu Ala Pro Leu Tyr Gly Gln Met Met Ile 
1               5                   10                  15      


Tyr Ala Lys Phe Asp Lys Asn Val Tyr Leu Pro Glu Asp Ala Glu Phe 
            20                  25                  30          


Tyr Phe Thr Tyr Asp Gly Ser His Gln Arg His Val Met Ile Ala Glu 
        35                  40                  45              


Arg Ile Glu Asp Asn Val Leu Gln Ser Ser Val Pro Gly His Gly Leu 
    50                  55                  60                  


Gln Glu Thr Val Thr Val Ser Val Cys Leu Cys Ser Glu Gly Tyr Ser 
65                  70                  75                  80  


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


Cys Arg Leu Ala Arg Leu Leu Val Thr Gln Ala Asn Arg Leu Thr Ala 
            100                 105                 110         


Cys Ser His Gln Thr Leu Leu Thr Pro Phe Ala Leu Thr Ala Gly Ala 
        115                 120                 125             


Leu Pro Ala Leu Asp Glu Glu Leu Val Leu Ala Leu Thr His Leu Glu 
    130                 135                 140                 


Leu Pro Leu Glu Trp Thr Val Leu Gly Ser Ser Ser Leu Glu Val Ser 
145                 150                 155                 160 


Ser His Arg Glu Ser Leu Leu His Leu Ala Met Arg Trp Gly Leu Ala 
                165                 170                 175     


Lys Leu Ser Gln Phe Phe Leu Cys Leu Pro Gly Gly Val Gln Ala Leu 
            180                 185                 190         


Ala Leu Pro Asn Glu Glu Gly Ala Thr Pro Leu Asp Leu Ala Leu Arg 
        195                 200                 205             


Glu Gly His Ser Lys Leu Val Glu Asp Val Thr Asn Phe Gln Gly Arg 
    210                 215                 220                 


Trp Ser Pro Ser Phe Ser Arg Val Gln Leu Ser Glu Glu Ala Ser Leu 
225                 230                 235                 240 


His Tyr 
        


