40:
1792:
464:
Transferrin receptor production depends on a similar mechanism. But this one has the opposite trigger, and the opposite ultimate effect. IRE-BPs without iron bind to the IREs on transferrin receptor mRNA. But those IREs have a different effect: When the IRE-BP binds to these sites, the binding not
452:
and for ferritin. Iron-responsive element-binding protein (IRE-BP) binds to these mRNA sequences. On its own, the IRE-BP binds to the IREs of ferritin and transferrin receptor mRNA. But, when iron binds to the IRE-BP, the IRE-BP changes shape with the result that the IRE-BPs can no longer bind the
468:
In low-iron conditions, IRE-BPs allow the cell to keep producing transferrin receptors. And more transferrin receptors make it easier for the cell to bring in more iron from transferrin-iron complexes circulating outside the cell. But, as iron binds to more and more IRE-BPs, they change shape and
394:, more commonly known as a rabbit. This protein has a couple of conformational changes associated with it to explain the alternative functions as either mRNA regulator or as an enzyme. This information was obtained from the RCSB protein data bank website.
400:
is less abundant than IRP1 in most cells. The strongest expression is in intestine and brain. Relative to IRP1, IRP2 has a 73-amino acid insertion, and this insertion mediates the IRP2 degradation in iron-replete cells. IRP2 is regulated by the F-Box
376:, is a bifunctional protein that functions as an iron-responsive element (IRE)-binding protein involved in the control of iron metabolism by binding mRNA to repress translation or degradation. It functions also as the cytoplasmic isoform of
453:
ferritin mRNA. This liberates the mRNA to direct the cell to make more ferritin. In other words, when there is high iron in the cell, the iron itself causes the cell to produce more iron storage molecules. (The IRE-BP is an
1296:
469:
unbind the transferrin receptor mRNA. The transferrin receptor mRNA is rapidly degraded without the IRE-BP attached to it. The cell stops producing transferrin receptors.
480:
molecules, more and more iron will bind to the IRE-BPs. That will stop transferrin receptor production. And iron-IRE-BP binding will also start ferritin production.
796:"Molecular characterization of a second iron-responsive element-binding protein, iron regulatory protein 2. Structure, function, and post-translational regulation"
217:
68:
878:
417:. Since iron is tightly bound to transferrin, cells throughout the body have receptors for transferrin-iron complexes on their surfaces. These receptors
428:
Cells have advanced mechanisms for sensing their own need for iron. In human cells, the best-characterized iron-sensing mechanism is the result of
1289:
1817:
1812:
840:"RCSB Protein Data Bank - Structure Summary for 2IPY - crystal structure of iron regulatory protein 1 in complex with ferritin H IRE-RNA"
483:
When the cell is low on iron, less and less iron will bind to IRE-BPs. The IRE-BPs without iron will bind to transferrin receptor mRNA.
241:
92:
380:. Aconitases are iron-sulfur proteins that require a 4Fe-4S cluster for their enzymatic activity, in which they catalyze conversion of
606:"Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress"
1282:
1511:
229:
80:
388:. This structure was based on x-ray crystal diffraction. The resolution was 2.80 Ă…. This protein was harvested from the species
1473:
1218:
222:
1376:
871:
1667:
73:
1406:
1396:
418:
1386:
1371:
846:
519:"Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs"
1782:
1652:
1768:
1755:
1742:
1729:
1716:
1703:
1690:
1464:
1445:
1421:
1323:
864:
755:"Iron regulates cytoplasmic levels of a novel iron-responsive element-binding protein without aconitase activity"
1662:
1616:
1559:
1391:
1310:
1254:
850:
133:
1564:
1259:
492:
441:
354:
665:"Characterization of a second RNA-binding protein in rodents with specificity for iron-responsive elements"
1121:
891:
429:
1274:
569:
Eisenstein RS (2000). "Iron regulatory proteins and the molecular control of mammalian iron metabolism".
234:
1585:
1504:
1236:
1027:
991:
908:
390:
358:
287:
85:
1657:
17:
1228:
1210:
970:
965:
960:
617:
449:
150:
465:
only allows for translation but also stabilizes the mRNA molecule so it can stay intact for longer.
458:
405:
which activate the ubiquitination and then the degradation of IRP2. IRP2 has no aconitase activity.
1621:
1478:
1381:
1367:
706:"Requirements for iron-regulated degradation of the RNA binding protein, iron regulatory protein 2"
1554:
1454:
1335:
1246:
795:
754:
664:
1822:
1430:
1411:
1192:
839:
817:
776:
735:
686:
645:
586:
548:
1600:
1595:
1569:
1497:
1108:
899:
807:
766:
725:
717:
676:
635:
625:
578:
538:
530:
291:
282:
145:
154:
1647:
1631:
1544:
1200:
1146:
982:
421:
both the protein and the iron attached to it. Once inside, the cell transfers the iron to
311:
174:
138:
621:
39:
1796:
1685:
1626:
928:
721:
534:
812:
771:
730:
705:
681:
543:
518:
1806:
1590:
1549:
1355:
1126:
1075:
640:
605:
1539:
1435:
1001:
582:
258:
109:
1763:
1698:
1534:
1327:
1314:
1183:
1090:
1085:
1058:
956:
951:
321:
184:
1791:
856:
1080:
947:
887:
385:
265:
116:
1737:
1711:
1401:
1360:
1345:
1068:
630:
497:
454:
377:
590:
821:
780:
739:
690:
649:
552:
1340:
1049:
1036:
1006:
996:
942:
917:
473:
422:
270:
121:
1350:
1169:
1164:
1131:
381:
794:
Samaniego F, Chin J, Iwai K, Rouault TA, Klausner RD (December 1994).
1750:
1520:
253:
104:
1724:
1306:
1136:
1116:
437:
414:
402:
1159:
1154:
1053:
937:
477:
445:
433:
246:
97:
1493:
1278:
860:
472:
When the cell has obtained more iron than it can bind up with
413:
All cells use some iron, and must get it from the circulating
1489:
1780:
1676:
1640:
1609:
1578:
1527:
1463:
1444:
1420:
1322:
1245:
1227:
1209:
1191:
1182:
1145:
1107:
1026:
1019:
981:
927:
916:
907:
898:
317:
307:
302:
281:
276:
264:
252:
240:
228:
216:
208:
203:
198:
180:
170:
165:
144:
132:
127:
115:
103:
91:
79:
67:
59:
51:
46:
32:
704:Iwai K, Klausner RD, Rouault TA (November 1995).
663:Henderson BR, Seiser C, KĂĽhn LC (December 1993).
457:; for a schematic drawing of the shape change,
564:
562:
1505:
1290:
872:
8:
440:to make proteins). Sequences of mRNA called
436:(the chemical instructions derived from DNA
1512:
1498:
1490:
1297:
1283:
1275:
1188:
1023:
924:
913:
904:
879:
865:
857:
753:Guo B, Yu Y, Leibold EA (September 1994).
299:
162:
38:
849:at the U.S. National Library of Medicine
811:
770:
729:
680:
639:
629:
542:
199:iron-responsive element-binding protein 2
847:Iron-Responsive+Element+Binding+Proteins
335:iron-responsive element-binding proteins
1787:
1064:Iron-responsive element-binding protein
517:Gray, N. K.; Hentze, M. W. (Aug 1994).
509:
18:Iron-responsive element binding protein
425:, the internal iron storage molecule.
195:
29:
7:
722:10.1002/j.1460-2075.1995.tb00219.x
604:Hentze MW, KĂĽhn LC (August 1996).
535:10.1002/j.1460-2075.1994.tb06699.x
25:
1790:
444:(IREs) are contained within the
1474:Carboxymethyloxysuccinate lyase
1219:Phosphoric acids and phosphates
1377:Methylglutaconyl-CoA hydratase
1:
1407:Uroporphyrinogen III synthase
1397:3-Isopropylmalate dehydratase
952:Ferroportin (SLC11A3/SLC40A1)
813:10.1016/S0021-9258(18)47367-X
772:10.1016/S0021-9258(19)51075-4
682:10.1016/S0021-9258(19)74253-7
583:10.1146/annurev.nutr.20.1.627
1818:Genes on human chromosome 15
610:Proc. Natl. Acad. Sci. U.S.A
357:(IREs) in the regulation of
1813:Genes on human chromosome 9
1424:: Acting on polysaccharides
1387:Cystathionine beta synthase
1372:3-Hydroxyacyl ACP dehydrase
1839:
1668:Michaelis–Menten kinetics
1045:
298:
161:
37:
1560:Diffusion-limited enzyme
1392:Porphobilinogen synthase
1255:Calcium-sensing receptor
1002:Calreticulin/mobilferrin
851:Medical Subject Headings
448:sequences that code for
442:iron-responsive elements
355:iron-responsive elements
1260:Calcium-binding protein
631:10.1073/pnas.93.16.8175
33:Iron Regulatory Protein
1448:: Acting on phosphates
419:engulf and internalize
1653:Eadie–Hofstee diagram
1586:Allosteric regulation
1237:Magnesium transporter
1028:Iron-binding proteins
992:Duodenal cytochrome B
450:transferrin receptors
391:Oryctolagus cuniculus
359:human iron metabolism
1663:Lineweaver–Burk plot
1229:Magnesium metabolism
1211:Phosphate metabolism
961:Transferrin receptor
430:post-transcriptional
1479:Hydroperoxide lyase
1382:Tryptophan synthase
1368:Enoyl-CoA hydratase
622:1996PNAS...93.8175H
1622:Enzyme superfamily
1555:Enzyme promiscuity
1455:Threonine synthase
1336:Carbonic anhydrase
1247:Calcium metabolism
1778:
1777:
1487:
1486:
1431:Hyaluronate lyase
1412:Nitrile hydratase
1272:
1271:
1268:
1267:
1193:Sodium metabolism
1178:
1177:
1109:Copper metabolism
1103:
1102:
1099:
1098:
1015:
1014:
529:(16): 3882–3891.
331:
330:
327:
326:
194:
193:
190:
189:
16:(Redirected from
1830:
1795:
1794:
1786:
1658:Hanes–Woolf plot
1601:Enzyme activator
1596:Enzyme inhibitor
1570:Enzyme catalysis
1514:
1507:
1500:
1491:
1313:4.2) (primarily
1299:
1292:
1285:
1276:
1189:
1024:
925:
914:
905:
900:Transition metal
892:Metal metabolism
881:
874:
867:
858:
843:
826:
825:
815:
806:(49): 30904–10.
791:
785:
784:
774:
765:(39): 24252–60.
750:
744:
743:
733:
701:
695:
694:
684:
675:(36): 27327–34.
660:
654:
653:
643:
633:
601:
595:
594:
566:
557:
556:
546:
514:
337:, also known as
300:
196:
163:
42:
30:
21:
1838:
1837:
1833:
1832:
1831:
1829:
1828:
1827:
1803:
1802:
1801:
1789:
1781:
1779:
1774:
1686:Oxidoreductases
1672:
1648:Enzyme kinetics
1636:
1632:List of enzymes
1605:
1574:
1545:Catalytic triad
1523:
1518:
1488:
1483:
1459:
1440:
1416:
1318:
1303:
1273:
1264:
1241:
1223:
1205:
1174:
1147:Zinc metabolism
1141:
1095:
1041:
1011:
983:Iron(III) oxide
977:
919:
909:Iron metabolism
894:
885:
838:
835:
830:
829:
793:
792:
788:
752:
751:
747:
703:
702:
698:
662:
661:
657:
616:(16): 8175–82.
603:
602:
598:
571:Annu. Rev. Nutr
568:
567:
560:
516:
515:
511:
506:
489:
411:
367:
28:
23:
22:
15:
12:
11:
5:
1836:
1834:
1826:
1825:
1820:
1815:
1805:
1804:
1800:
1799:
1776:
1775:
1773:
1772:
1759:
1746:
1733:
1720:
1707:
1694:
1680:
1678:
1674:
1673:
1671:
1670:
1665:
1660:
1655:
1650:
1644:
1642:
1638:
1637:
1635:
1634:
1629:
1624:
1619:
1613:
1611:
1610:Classification
1607:
1606:
1604:
1603:
1598:
1593:
1588:
1582:
1580:
1576:
1575:
1573:
1572:
1567:
1562:
1557:
1552:
1547:
1542:
1537:
1531:
1529:
1525:
1524:
1519:
1517:
1516:
1509:
1502:
1494:
1485:
1484:
1482:
1481:
1476:
1470:
1468:
1461:
1460:
1458:
1457:
1451:
1449:
1442:
1441:
1439:
1438:
1433:
1427:
1425:
1418:
1417:
1415:
1414:
1409:
1404:
1399:
1394:
1389:
1384:
1379:
1374:
1365:
1364:
1363:
1358:
1348:
1343:
1338:
1332:
1330:
1320:
1319:
1305:Carbon–oxygen
1304:
1302:
1301:
1294:
1287:
1279:
1270:
1269:
1266:
1265:
1263:
1262:
1257:
1251:
1249:
1243:
1242:
1240:
1239:
1233:
1231:
1225:
1224:
1222:
1221:
1215:
1213:
1207:
1206:
1204:
1203:
1197:
1195:
1186:
1180:
1179:
1176:
1175:
1173:
1172:
1167:
1162:
1157:
1151:
1149:
1143:
1142:
1140:
1139:
1134:
1129:
1124:
1119:
1113:
1111:
1105:
1104:
1101:
1100:
1097:
1096:
1094:
1093:
1088:
1083:
1078:
1073:
1072:
1071:
1061:
1056:
1046:
1043:
1042:
1040:
1039:
1033:
1031:
1021:
1017:
1016:
1013:
1012:
1010:
1009:
1004:
999:
994:
988:
986:
979:
978:
976:
975:
974:
973:
968:
954:
945:
940:
938:DMT1 (SLC11A2)
934:
932:
929:Iron(II) oxide
922:
911:
902:
896:
895:
886:
884:
883:
876:
869:
861:
855:
854:
844:
834:
833:External links
831:
828:
827:
786:
745:
716:(21): 5350–7.
696:
655:
596:
558:
508:
507:
505:
502:
501:
500:
495:
488:
485:
432:regulation of
410:
409:Iron transport
407:
366:
363:
329:
328:
325:
324:
319:
315:
314:
309:
305:
304:
296:
295:
285:
279:
278:
274:
273:
268:
262:
261:
256:
250:
249:
244:
238:
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226:
225:
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214:
213:
210:
206:
205:
201:
200:
192:
191:
188:
187:
182:
178:
177:
172:
168:
167:
159:
158:
148:
142:
141:
136:
130:
129:
125:
124:
119:
113:
112:
107:
101:
100:
95:
89:
88:
83:
77:
76:
71:
65:
64:
61:
57:
56:
53:
49:
48:
44:
43:
35:
34:
27:Protein family
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
1835:
1824:
1821:
1819:
1816:
1814:
1811:
1810:
1808:
1798:
1793:
1788:
1784:
1770:
1766:
1765:
1760:
1757:
1753:
1752:
1747:
1744:
1740:
1739:
1734:
1731:
1727:
1726:
1721:
1718:
1714:
1713:
1708:
1705:
1701:
1700:
1695:
1692:
1688:
1687:
1682:
1681:
1679:
1675:
1669:
1666:
1664:
1661:
1659:
1656:
1654:
1651:
1649:
1646:
1645:
1643:
1639:
1633:
1630:
1628:
1627:Enzyme family
1625:
1623:
1620:
1618:
1615:
1614:
1612:
1608:
1602:
1599:
1597:
1594:
1592:
1591:Cooperativity
1589:
1587:
1584:
1583:
1581:
1577:
1571:
1568:
1566:
1563:
1561:
1558:
1556:
1553:
1551:
1550:Oxyanion hole
1548:
1546:
1543:
1541:
1538:
1536:
1533:
1532:
1530:
1526:
1522:
1515:
1510:
1508:
1503:
1501:
1496:
1495:
1492:
1480:
1477:
1475:
1472:
1471:
1469:
1466:
1462:
1456:
1453:
1452:
1450:
1447:
1443:
1437:
1434:
1432:
1429:
1428:
1426:
1423:
1419:
1413:
1410:
1408:
1405:
1403:
1400:
1398:
1395:
1393:
1390:
1388:
1385:
1383:
1380:
1378:
1375:
1373:
1369:
1366:
1362:
1359:
1357:
1354:
1353:
1352:
1349:
1347:
1344:
1342:
1339:
1337:
1334:
1333:
1331:
1329:
1325:
1321:
1316:
1312:
1308:
1300:
1295:
1293:
1288:
1286:
1281:
1280:
1277:
1261:
1258:
1256:
1253:
1252:
1250:
1248:
1244:
1238:
1235:
1234:
1232:
1230:
1226:
1220:
1217:
1216:
1214:
1212:
1208:
1202:
1199:
1198:
1196:
1194:
1190:
1187:
1185:
1181:
1171:
1168:
1166:
1163:
1161:
1158:
1156:
1153:
1152:
1150:
1148:
1144:
1138:
1135:
1133:
1130:
1128:
1127:Ceruloplasmin
1125:
1123:
1120:
1118:
1115:
1114:
1112:
1110:
1106:
1092:
1089:
1087:
1084:
1082:
1079:
1077:
1076:Ceruloplasmin
1074:
1070:
1067:
1066:
1065:
1062:
1060:
1057:
1055:
1051:
1048:
1047:
1044:
1038:
1035:
1034:
1032:
1029:
1025:
1022:
1018:
1008:
1005:
1003:
1000:
998:
995:
993:
990:
989:
987:
984:
980:
972:
969:
967:
964:
963:
962:
958:
955:
953:
949:
946:
944:
941:
939:
936:
935:
933:
930:
926:
923:
921:
918:Absorption in
915:
912:
910:
906:
903:
901:
897:
893:
889:
882:
877:
875:
870:
868:
863:
862:
859:
852:
848:
845:
841:
837:
836:
832:
823:
819:
814:
809:
805:
801:
800:J. Biol. Chem
797:
790:
787:
782:
778:
773:
768:
764:
760:
759:J. Biol. Chem
756:
749:
746:
741:
737:
732:
727:
723:
719:
715:
711:
707:
700:
697:
692:
688:
683:
678:
674:
670:
669:J. Biol. Chem
666:
659:
656:
651:
647:
642:
637:
632:
627:
623:
619:
615:
611:
607:
600:
597:
592:
588:
584:
580:
576:
572:
565:
563:
559:
554:
550:
545:
540:
536:
532:
528:
524:
520:
513:
510:
503:
499:
496:
494:
491:
490:
486:
484:
481:
479:
475:
470:
466:
462:
460:
456:
451:
447:
443:
439:
435:
431:
426:
424:
420:
416:
408:
406:
404:
399:
395:
393:
392:
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19:
1764:Translocases
1761:
1748:
1735:
1722:
1709:
1699:Transferases
1696:
1683:
1540:Binding site
1436:Pectin lyase
1328:Hydro-Lyases
1315:dehydratases
1063:
803:
799:
789:
762:
758:
748:
713:
709:
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672:
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350:
346:
342:
338:
334:
332:
290:
153:
60:Alt. symbols
1535:Active site
1201:Na/K-ATPase
1184:Electrolyte
1091:Lactoferrin
1086:Hemosiderin
1059:Hemojuvelin
957:Transferrin
312:Swiss-model
204:Identifiers
175:Swiss-model
47:Identifiers
1807:Categories
1738:Isomerases
1712:Hydrolases
1579:Regulation
948:Hephaestin
888:Metabolism
577:: 627–62.
504:References
386:isocitrate
353:, bind to
308:Structures
303:Search for
277:Other data
171:Structures
166:Search for
128:Other data
1617:EC number
1402:Urocanase
1361:Enolase 2
1346:Aconitase
1069:Aconitase
498:Aconitase
455:aconitase
378:aconitase
259:NM_004136
218:NCBI gene
134:EC number
110:NM_002197
69:NCBI gene
1823:EC 4.2.1
1641:Kinetics
1565:Cofactor
1528:Activity
1341:Fumarase
1050:Hepcidin
1037:Ferritin
1007:Ferritin
997:Integrin
943:Ferritin
920:duodenum
591:10940348
487:See also
474:ferritin
459:see here
423:ferritin
365:Function
322:InterPro
185:InterPro
1797:Biology
1751:Ligases
1521:Enzymes
1467:: Other
1351:Enolase
1170:SLC39A4
1165:SLC30A1
1132:SLC31A1
822:7983023
781:7523370
740:7489724
691:8262972
650:8710843
618:Bibcode
553:8070415
382:citrate
318:Domains
288:Chr. 15
266:UniProt
181:Domains
139:4.2.1.3
117:UniProt
1783:Portal
1725:Lyases
1465:4.2.99
1307:lyases
853:(MeSH)
820:
779:
738:
731:394644
728:
710:EMBO J
689:
648:
638:
589:
551:
544:395301
541:
523:EMBO J
339:IRE-BP
271:P48200
254:RefSeq
247:147582
209:Symbol
151:Chr. 9
122:P21399
105:RefSeq
98:100880
52:Symbol
1677:Types
1446:4.2.3
1422:4.2.2
1356:Alpha
1324:4.2.1
1137:ATOX1
1122:ATP7B
1117:ATP7A
1020:Other
641:38642
438:genes
415:blood
403:FBXL5
372:, or
292:q25.1
283:Locus
212:IREB2
155:p21.1
146:Locus
63:IREB1
1769:list
1762:EC7
1756:list
1749:EC6
1743:list
1736:EC5
1730:list
1723:EC4
1717:list
1710:EC3
1704:list
1697:EC2
1691:list
1684:EC1
1160:TMC8
1155:TMC6
1054:HAMP
971:TFR2
966:TFR1
818:PMID
777:PMID
736:PMID
687:PMID
646:PMID
587:PMID
549:PMID
478:heme
446:mRNA
434:mRNA
398:IRP2
374:IRP1
370:ACO1
349:and
343:IRBP
333:The
242:OMIM
235:6115
230:HGNC
223:3658
93:OMIM
81:HGNC
55:ACO1
1081:HFE
959:to
808:doi
804:269
767:doi
763:269
726:PMC
718:doi
677:doi
673:268
636:PMC
626:doi
579:doi
539:PMC
531:doi
493:IRE
476:or
461:).
384:to
351:IFR
347:IRP
86:117
1809::
1326::
1311:EC
890::
816:.
802:.
798:.
775:.
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734:.
724:.
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712:.
708:.
685:.
671:.
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634:.
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612:.
608:.
585:.
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561:^
547:.
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521:.
361:.
345:,
341:,
74:48
1785::
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1754:(
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1728:(
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1715:(
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1702:(
1693:)
1689:(
1513:e
1506:t
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1370:/
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1309:(
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866:v
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810::
783:.
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679::
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628::
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593:.
581::
555:.
533::
20:)
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