675:
monomer with non-specific protein-DNA interactions. The coding end is highly distorted with one base flipped out from the DNA duplex in the active center, which facilitates the hairpin formation by a potential two-metal ion catalytic mechanism. The 12-RSS and 23-RSS intermediates are highly bent and asymmetrically bound to the synaptic RAG complex with the nonamer binding domain dimer tilts towards the nonamer of the 12-RSS but away from the nonamer of the 23-RSS, which emphasizes the 12/23 rule. Two HMGB1 molecules bind at each side of 12-RSS and 23-RSS to stabilize the highly bent RSSs. These structures elaborate the molecular mechanisms for DNA recognition, catalysis and the unique synapsis underlying the 12/23 rule, provide new insights into the RAG-associated human diseases, and represent a most complete set of complexes in the catalytic pathways of any DDE family recombinases, transposases or integrases.
572:(foreign proteins and carbohydrates) without attacking the body itself. The human genome has at most 30,000 genes, and yet it generates millions of different antibodies, which allows it to be able to respond to invasion from millions of different antigens. The immune system generates this diversity of antibodies by shuffling, cutting and recombining a few hundred genes (the VDJ genes) to create millions of permutations, in a process called
689:
622:. RAG-1 was shown to inefficiently induce recombination activity of the VDJ genes when isolated and transfected into fibroblast samples. When RAG-1 was cotransfected with RAG-2, recombination frequency increased by a 1000-fold. This finding has fostered the newly revised theory that RAG genes may not only assist in VDJ recombination, but rather, directly induce the recombinations of the VDJ genes.
837:
RAG1/2-like pair may have been present in its current form in most metazoan lineages and was lost in the jawless vertebrate and urochordate lineages. There is no evidence that the V(D)J recombination system arose earlier than the vertebrate lineage. It is currently hypothesized that the invasion of RAG1/2 is the most important evolutionary event in terms of shaping the gnathostome
772:(a moth). The terminal inverted repeats (TIR) in lancelet ProtoRAG have a heptamer-spacer-nonamer structure similar to that of RSS, but the moth ProtoRAG lacks a nonamer. The nonamer-binding regions and the nonamer sequences of lancelet ProtoRAG and animal RAG are different enough to not recognize each other. The structure of the lancelet protoRAG has been solved (
854:
would provide the genetic raw material for the development of the adaptive immune system, and the development of endothelial tissue, greater metabolic activity, and a decreased blood volume-to-body weight ratio, all of which are more specialized in vertebrates than invertebrates and facilitate adaptive immune responses.
836:
is due to horizontal gene transfer or gene loss in certain phylogenetic groups due to conventional vertical transmission. Recent analysis has shown the RAG phylogeny to be gradual and directional, suggesting an evolutionary path that relies on vertical transmission. This hypothesis suggests that the
674:
of the 12-RSS and 23-RSS intermediates with base specific interactions in the heptamer of the signal end. The first base of the heptamer in the signal end is flipped out to avoid the clash in the active center. Each coding end of the nicked-RSS intermediate is stabilized exclusively by one RAG1-RAG2
617:
The RAG proteins initiate V(D)J recombination, which is essential for the maturation of pre-B and pre-T cells. Activated mature B cells also possess two other remarkable, RAG-independent phenomena of manipulating their own DNA: so-called class-switch recombination (AKA isotype switching) and somatic
853:
It is still unclear what forces led to the development of a RAG1/2-mediated immune system exclusively in jawed vertebrates and not in any invertebrate species that also acquired the RAG1/2-containing transposon. Current hypotheses include two whole-genome duplication events in vertebrates, which
669:
structures of the synaptic RAG complexes reveal a closed dimer conformation with generation of new intermolecular interactions between two RAG1-RAG2 monomers upon DNA binding, compared to the Apo-RAG complex which constitutes as an open conformation. Both RAG1 molecules in the closed dimer are
594:(RSS). They do this in two steps. They initially introduce a ‘nick’ in the 5' (upstream) end of the RSS heptamer (a conserved region of 7 nucleotides) that is adjacent to the coding sequence, leaving behind a specific biochemical structure on this region of DNA: a 3'-
634:
and mouse RAG-2 contains 527 amino acids. The enzymatic activity of the RAG proteins is concentrated largely in a core region; Residues 384–1008 of RAG-1 and residues 1–387 of RAG-2 retain most of the DNA cleavage activity. The RAG-1 core contains three
655:, the major active site for DNA cleavage. These residues are critical for nicking the DNA strand and for forming the DNA hairpin. Residues 384–454 of RAG-1 comprise a nonamer-binding region (NBR) that specifically binds the conserved nonamer (9
831:
family transposon invaded multiple times in non-vertebrate species, and invaded the ancestral jawed vertebrate genome about 500 MYA. It is hypothesized that the absence of RAG-like genes in jawless vertebrates and
737:
family members include an N-terminal sequence found in RAG1 suggesting the N-terminal of RAG1 came from a separate element. The N-terminal region of RAG1 has been found in the transposable element
576:. RAG-1 and RAG-2 are proteins at the ends of VDJ genes that separate, shuffle, and rejoin the VDJ genes. This shuffling takes place inside B cells and T cells during their maturation.
785:
Although the transposon origins of these genes are well-established, there is still no consensus on when the ancestral RAG1/2 locus became present in the vertebrate genome. Because
1342:
Morales Poole JR, Huang SF, Xu A, Bayet J, Pontarotti P (June 2017). "The RAG transposon is active through the deuterostome evolution and domesticated in jawed vertebrates".
659:) of the RSS and the central domain (amino acids 528–760) of RAG-1 binds specifically to the RSS heptamer. The core region of RAG-2 is predicted to form a six-bladed
484:
375:
610:-group (that is sitting between the RSS and the gene segment on the opposite strand). This produces a 5'-phosphorylated double-stranded break at the RSS and a
1832:
De P, Rodgers KK (Aug 2004). "Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1".
1452:
Kasahara M, Suzuki T, Pasquier LD (Feb 2004). "On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates".
1980:
1293:
Huang S, Tao X, Yuan S, Zhang Y, Li P, Beilinson HA, Zhang Y, Yu W, Pontarotti P, Escriva H, Le
Petillon Y, Liu X, Chen S, Schatz DG, Xu A (June 2016).
182:
41:
986:
Oettinger MA, Schatz DG, Gorka C, Baltimore D (Jun 1990). "RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination".
618:
hypermutation (AKA affinity maturation). Current studies have indicated that RAG-1 and RAG-2 must work in a synergistic manner to activate
614:
closed hairpin at the coding end. The RAG proteins remain at these junctions until other enzymes (notably, TDT) repair the DNA breaks.
747:, which contains the entire RAG1 N-terminal. It is likely that the full RAG1 structure was derived from the recombination between a
544:
during their developmental stages. The enzymes encoded by these genes, RAG-1 and RAG-2, are essential to the generation of mature
1973:
187:
46:
2409:
504:
395:
1395:
Zhang Y, Cheng TC, Huang G, Lu Q, Surleac MD, Mandell JD, Pontarotti P, Petrescu AJ, Xu A, Xiong Y, Schatz DG (May 2019).
206:
65:
606:) group at the RSS end. The next step couples these chemical groups, binding the OH-group (on the coding end) to the PO
1966:
703:
789:(a class of jawless fish) lack a core RAG1 element, it was traditionally assumed that RAG1 invaded after the agnathan/
2312:
868:
194:
53:
1185:"Guardian of the Genome: An Alternative RAG/Transib Co-Evolution Hypothesis for the Origin of V(D)J Recombination"
1924:"The Accidental Immune System; Long ago, a wandering piece of DNA—perhaps from a microbe—created a key strategy"
2307:
492:
383:
2250:
798:
591:
842:
793:
split 1001 to 590 million years ago (MYA). However, the core sequence of RAG1 has been identified in the
838:
199:
58:
2136:
1547:
Holland LZ, Albalat R, Azumi K, Benito-Gutiérrez E, Blow MJ, Bronner-Fraser M, et al. (Jul 2008).
488:
379:
1923:
1958:
666:
758:
A transposon with RAG2 arranged next to RAG1 has been identified in the purple sea urchin. Active
2316:
2074:
1652:"Identification of RAG-like transposons in protostomes suggests their ancient bilaterian origin"
2414:
2338:
2056:
1992:
807:
782:), providing some understanding on what changes lead to the domestication of RAG genes.
553:
2285:
2141:
2119:
630:
As with many enzymes, RAG proteins are fairly large. For example, mouse RAG-1 contains 1040
252:
111:
2419:
2302:
2235:
2146:
2070:
1503:
1408:
1351:
995:
579:
RAG enzymes work as a multi-subunit complex to induce cleavage of a single double stranded
471:
362:
1871:"RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons"
1650:
Martin EC, Vicari C, Tsakou-Ngouafo L, Pontarotti P, Petrescu AJ, Schatz DG (2020-05-06).
1080:"RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons"
276:
256:
135:
115:
8:
2362:
2297:
2280:
2114:
2032:
768:
743:
671:
619:
573:
1507:
1412:
999:
702:
Please expand the section to include this information. Further details may exist on the
524:
that plays important roles in the rearrangement and recombination of the genes encoding
2182:
1946:
1897:
1870:
1857:
1820:
1764:
1737:
1678:
1651:
1622:
1597:
1573:
1548:
1524:
1491:
1429:
1396:
1377:
1319:
1294:
1267:
1240:
1211:
1184:
1155:
1130:
1106:
1079:
1055:
1031:"Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures"
1030:
963:
938:
919:
1295:"Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination"
2230:
1996:
1902:
1849:
1845:
1812:
1808:
1769:
1718:
1683:
1627:
1578:
1529:
1469:
1434:
1369:
1324:
1272:
1216:
1160:
1111:
1060:
1011:
968:
911:
907:
774:
479:
370:
1861:
1824:
1598:"Molluscan mobile elements similar to the vertebrate Recombination-Activating Genes"
1381:
1131:"Molluscan mobile elements similar to the vertebrate Recombination-Activating Genes"
923:
433:
324:
2350:
2290:
2262:
2257:
2225:
2212:
2202:
1938:
1892:
1882:
1841:
1804:
1759:
1749:
1710:
1673:
1663:
1617:
1609:
1568:
1560:
1519:
1511:
1461:
1424:
1416:
1361:
1314:
1306:
1262:
1252:
1206:
1196:
1150:
1142:
1101:
1091:
1050:
1042:
1003:
958:
950:
903:
467:
358:
247:
106:
2245:
1887:
1549:"The amphioxus genome illuminates vertebrate origins and cephalochordate biology"
1096:
823:
and protostomes including oysters, mussels, ribbon worms, and the non-bilaterian
811:(Florida lancelet). Sequences with homology to RAG1 have also been identified in
587:
529:
521:
445:
336:
223:
82:
286:
145:
2272:
2217:
2158:
2078:
2051:
1668:
1613:
1496:
Proceedings of the
National Academy of Sciences of the United States of America
1310:
1241:"Evolution of the RAG1-RAG2 locus: both proteins came from the same transposon"
1146:
1046:
863:
660:
652:
525:
1754:
1714:
1420:
1365:
1257:
1201:
2403:
2240:
2129:
1955:
A simple explanation of recombination activating gene for the general reader.
1738:"Was the evolutionary road towards adaptive immunity paved with endothelium?"
1465:
1397:"Transposon molecular domestication and the evolution of the RAG recombinase"
1515:
1007:
2207:
2192:
2187:
2124:
2022:
1906:
1853:
1816:
1773:
1722:
1687:
1631:
1582:
1533:
1473:
1438:
1373:
1328:
1276:
1220:
1164:
1115:
1064:
972:
915:
1564:
1015:
790:
724:
723:
Based on core sequence homology, it is believed that RAG1 evolved from a
541:
235:
94:
954:
762:
transposons with both RAG1 and RAG2 ("ProtoRAG") has been discovered in
2330:
2083:
1989:
1950:
892:"The taming of a transposon: V(D)J recombination and the immune system"
794:
656:
631:
565:
230:
89:
778:
2388:
2093:
1988:
786:
599:
1942:
1649:
891:
568:
immune system, each antibody is customized to attack one particular
2378:
2163:
2151:
2109:
2063:
2027:
1792:
1546:
1356:
833:
824:
803:
611:
595:
440:
331:
1490:
Fugmann SD, Messier C, Novack LA, Cameron RA, Rast JP (Mar 2006).
2383:
2197:
2046:
2017:
1793:"Recombination-activating gene proteins: more regulation, please"
1029:
Ru H, Chambers MG, Fu TM, Tong AB, Liao M, Wu H (November 2015).
729:
584:
569:
688:
663:
structure that appears less specific than RAG-1 for its target.
211:
70:
2355:
2343:
2088:
2039:
636:
549:
545:
499:
390:
218:
77:
985:
939:"Human RAG mutations: biochemistry and clinical implications"
552:, two types of lymphocyte that are crucial components of the
1735:
1705:. Hematopoietic cell death/Immunogenetics/Transplantation.
1489:
537:
533:
461:
428:
352:
319:
175:
160:
34:
19:
1492:"An ancient evolutionary origin of the Rag1/2 gene locus"
1341:
1182:
580:
532:
molecules. There are two recombination-activating genes
1701:
Kasahara M (Oct 2007). "The 2R hypothesis: an update".
936:
1451:
937:
Notarangelo LD, Kim MS, Walter JE, Lee YN (Mar 2016).
1736:
van
Niekerk G, Davis T, Engelbrecht AM (2015-09-04).
1602:
1135:
1394:
1292:
1183:Yakovenko I, Agronin J, Smith LC, Oren M (2021).
2401:
1234:
1232:
1230:
1178:
1176:
1174:
1028:
1485:
1483:
1238:
1868:
1645:
1643:
1641:
1288:
1286:
1077:
1974:
1227:
1171:
540:, whose cellular expression is restricted to
1595:
1480:
1128:
889:
1638:
1283:
1981:
1967:
1896:
1886:
1831:
1763:
1753:
1677:
1667:
1621:
1572:
1523:
1428:
1355:
1318:
1266:
1256:
1210:
1200:
1154:
1105:
1095:
1054:
962:
1790:
1700:
885:
883:
2402:
1921:
1239:Kapitonov VV, Koonin EV (2015-04-28).
1022:
598:(OH) group at the coding end and a 5'-
1962:
848:
880:
682:
1078:Kapitonov VV, Jurka J (June 2005).
827:. These findings indicate that the
13:
1869:Kapitonov VV, Jurka J (Jun 2005).
1783:
410:Recombination-activating protein 1
301:Recombination-activating protein 2
14:
2431:
1915:
1846:10.1111/j.0105-2896.2004.00154.x
1809:10.1111/j.0105-2896.2004.00164.x
1596:Panchin Y, Moroz LL (May 2008).
1129:Panchin Y, Moroz LL (May 2008).
908:10.1111/j.0105-2896.2004.00168.x
890:Jones JM, Gellert M (Aug 2004).
869:Severe combined immunodeficiency
687:
1729:
1694:
1589:
1540:
1445:
1388:
1335:
161:recombination-activating gene 2
20:recombination-activating gene 1
2308:Immunoglobulin class switching
1122:
1071:
979:
930:
590:coding segment and a flanking
518:recombination-activating genes
1:
1703:Current Opinion in Immunology
874:
799:Strongylocentrotus purpuratus
592:recombination signal sequence
583:(dsDNA) molecule between the
456:Available protein structures:
347:Available protein structures:
2410:Genes on human chromosome 11
1888:10.1371/journal.pbio.0030181
1097:10.1371/journal.pbio.0030181
843:variable lymphocyte receptor
700:about Specifics in 30971819.
678:
651:) in what is called the DDE
625:
7:
857:
559:
10:
2436:
2137:Polyclonal B cell response
1922:Travis J (November 1998).
1669:10.1186/s13100-020-00214-y
1614:10.1016/j.bbrc.2008.02.097
1311:10.1016/j.cell.2016.05.032
1147:10.1016/j.bbrc.2008.02.097
1047:10.1016/j.cell.2015.10.055
943:Nature Reviews. Immunology
2371:
2329:
2271:
2172:
2102:
2010:
2003:
1755:10.1186/s13062-015-0079-0
1715:10.1016/j.coi.2007.07.009
1421:10.1038/s41586-019-1093-7
1366:10.1007/s00251-017-0979-5
1258:10.1186/s13062-015-0055-8
1202:10.3389/fimmu.2021.709165
802:(purple sea urchin), the
520:(RAGs) encode parts of a
498:
478:
460:
455:
451:
439:
427:
419:
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409:
389:
369:
351:
346:
342:
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229:
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205:
193:
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159:
141:
131:
126:
122:
105:
100:
88:
76:
64:
52:
40:
30:
25:
18:
1791:Sadofsky MJ (Aug 2004).
1466:10.1016/j.it.2003.11.005
819:(sea star), the mollusk
667:Cryo-electron microscopy
1516:10.1073/Pnas.0509720103
1189:Frontiers in Immunology
1008:10.1126/science.2360047
766:(Chinese lancelet) and
2251:Tolerance in pregnancy
1993:adaptive immune system
839:adaptive immune system
808:Branchiostoma floridae
698:is missing information
554:adaptive immune system
2286:Somatic hypermutation
2120:Polyclonal antibodies
2115:Monoclonal antibodies
1834:Immunological Reviews
1797:Immunological Reviews
1565:10.1101/gr.073676.107
896:Immunological Reviews
813:Lytechinus veriegatus
2303:Junctional diversity
2071:Antigen presentation
1454:Trends in Immunology
821:Aplysia californica,
815:(green sea urchin),
2298:V(D)J recombination
2281:Affinity maturation
2033:Antigenic variation
1508:2006PNAS..103.3728F
1413:2019Natur.569...79Z
1000:1990Sci...248.1517O
955:10.1038/nri.2016.28
769:Psectrotarsia flava
744:Aplysia californica
672:cooperative binding
574:V(D)J recombination
849:Selective pressure
2397:
2396:
2325:
2324:
2075:professional APCs
994:(4962): 1517–23.
841:vs. the agnathan
741:in the sea slug,
721:
720:
620:VDJ recombination
514:
513:
510:
509:
505:structure summary
405:
404:
401:
400:
396:structure summary
296:
295:
292:
291:
155:
154:
151:
150:
2427:
2291:Clonal selection
2263:Immune privilege
2258:Immunodeficiency
2213:Cross-reactivity
2203:Hypersensitivity
2008:
2007:
1983:
1976:
1969:
1960:
1959:
1954:
1928:
1910:
1900:
1890:
1865:
1828:
1778:
1777:
1767:
1757:
1733:
1727:
1726:
1698:
1692:
1691:
1681:
1671:
1647:
1636:
1635:
1625:
1593:
1587:
1586:
1576:
1544:
1538:
1537:
1527:
1487:
1478:
1477:
1449:
1443:
1442:
1432:
1392:
1386:
1385:
1359:
1339:
1333:
1332:
1322:
1290:
1281:
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1270:
1260:
1236:
1225:
1224:
1214:
1204:
1180:
1169:
1168:
1158:
1126:
1120:
1119:
1109:
1099:
1075:
1069:
1068:
1058:
1041:(5): 1138–1152.
1026:
1020:
1019:
983:
977:
976:
966:
934:
928:
927:
887:
781:
733:superfamily. No
716:
713:
707:
691:
683:
670:involved in the
453:
452:
407:
406:
344:
343:
298:
297:
265:
264:
157:
156:
124:
123:
16:
15:
2435:
2434:
2430:
2429:
2428:
2426:
2425:
2424:
2400:
2399:
2398:
2393:
2367:
2321:
2267:
2246:Clonal deletion
2174:
2168:
2098:
1999:
1987:
1943:10.2307/4010948
1937:(19): 302–303.
1926:
1918:
1913:
1786:
1784:Further reading
1781:
1734:
1730:
1699:
1695:
1648:
1639:
1594:
1590:
1553:Genome Research
1545:
1541:
1502:(10): 3728–33.
1488:
1481:
1450:
1446:
1407:(7754): 79–84.
1393:
1389:
1340:
1336:
1291:
1284:
1237:
1228:
1181:
1172:
1127:
1123:
1076:
1072:
1027:
1023:
984:
980:
935:
931:
888:
881:
877:
860:
851:
773:
717:
711:
708:
701:
692:
681:
650:
646:
642:
628:
609:
605:
562:
530:T cell receptor
522:protein complex
12:
11:
5:
2433:
2423:
2422:
2417:
2412:
2395:
2394:
2392:
2391:
2386:
2381:
2375:
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2347:
2346:
2335:
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2322:
2320:
2319:
2310:
2305:
2300:
2295:
2294:
2293:
2288:
2277:
2275:
2273:Immunogenetics
2269:
2268:
2266:
2265:
2260:
2255:
2254:
2253:
2248:
2243:
2238:
2233:
2221:
2220:
2218:Co-stimulation
2215:
2210:
2205:
2200:
2195:
2190:
2185:
2178:
2176:
2170:
2169:
2167:
2166:
2161:
2159:Immune complex
2155:
2154:
2149:
2144:
2139:
2134:
2133:
2132:
2127:
2122:
2117:
2106:
2104:
2100:
2099:
2097:
2096:
2091:
2086:
2081:
2079:Dendritic cell
2067:
2066:
2061:
2060:
2059:
2057:Conformational
2054:
2043:
2042:
2037:
2036:
2035:
2030:
2025:
2014:
2012:
2005:
2001:
2000:
1986:
1985:
1978:
1971:
1963:
1957:
1956:
1917:
1916:External links
1914:
1912:
1911:
1866:
1829:
1787:
1785:
1782:
1780:
1779:
1742:Biology Direct
1728:
1693:
1637:
1588:
1559:(7): 1100–11.
1539:
1479:
1444:
1387:
1357:10.1101/100735
1350:(6): 391–400.
1344:Immunogenetics
1334:
1282:
1245:Biology Direct
1226:
1170:
1141:(3): 818–823.
1121:
1070:
1021:
978:
929:
878:
876:
873:
872:
871:
866:
864:Omenn syndrome
859:
856:
850:
847:
817:Patiria minata
719:
718:
695:
693:
686:
680:
677:
661:beta-propeller
648:
644:
640:
627:
624:
607:
603:
561:
558:
526:immunoglobulin
512:
511:
508:
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496:
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482:
476:
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38:
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32:
28:
27:
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9:
6:
4:
3:
2:
2432:
2421:
2418:
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2415:Immune system
2413:
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2279:
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2270:
2264:
2261:
2259:
2256:
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2241:Clonal anergy
2239:
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2234:
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2223:
2222:
2219:
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2165:
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2157:
2156:
2153:
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2148:
2145:
2143:
2140:
2138:
2135:
2131:
2130:Microantibody
2128:
2126:
2123:
2121:
2118:
2116:
2113:
2112:
2111:
2108:
2107:
2105:
2101:
2095:
2092:
2090:
2087:
2085:
2082:
2080:
2076:
2072:
2069:
2068:
2065:
2062:
2058:
2055:
2053:
2050:
2049:
2048:
2045:
2044:
2041:
2038:
2034:
2031:
2029:
2026:
2024:
2021:
2020:
2019:
2016:
2015:
2013:
2009:
2006:
2002:
1998:
1994:
1991:
1984:
1979:
1977:
1972:
1970:
1965:
1964:
1961:
1952:
1948:
1944:
1940:
1936:
1932:
1925:
1920:
1919:
1908:
1904:
1899:
1894:
1889:
1884:
1880:
1876:
1872:
1867:
1863:
1859:
1855:
1851:
1847:
1843:
1839:
1835:
1830:
1826:
1822:
1818:
1814:
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1802:
1798:
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1775:
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1761:
1756:
1751:
1747:
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1732:
1724:
1720:
1716:
1712:
1709:(5): 547–52.
1708:
1704:
1697:
1689:
1685:
1680:
1675:
1670:
1665:
1661:
1657:
1653:
1646:
1644:
1642:
1633:
1629:
1624:
1619:
1615:
1611:
1608:(3): 818–23.
1607:
1603:
1599:
1592:
1584:
1580:
1575:
1570:
1566:
1562:
1558:
1554:
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1521:
1517:
1513:
1509:
1505:
1501:
1497:
1493:
1486:
1484:
1475:
1471:
1467:
1463:
1460:(2): 105–11.
1459:
1455:
1448:
1440:
1436:
1431:
1426:
1422:
1418:
1414:
1410:
1406:
1402:
1398:
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1371:
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1363:
1358:
1353:
1349:
1345:
1338:
1330:
1326:
1321:
1316:
1312:
1308:
1305:(1): 102–14.
1304:
1300:
1296:
1289:
1287:
1278:
1274:
1269:
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1254:
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1125:
1117:
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1103:
1098:
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1074:
1066:
1062:
1057:
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1044:
1040:
1036:
1032:
1025:
1017:
1013:
1009:
1005:
1001:
997:
993:
989:
982:
974:
970:
965:
960:
956:
952:
949:(4): 234–46.
948:
944:
940:
933:
925:
921:
917:
913:
909:
905:
901:
897:
893:
886:
884:
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870:
867:
865:
862:
861:
855:
846:
844:
840:
835:
830:
826:
822:
818:
814:
810:
809:
805:
801:
800:
796:
792:
788:
783:
780:
776:
771:
770:
765:
761:
756:
754:
750:
746:
745:
740:
736:
732:
731:
726:
715:
705:
699:
696:This section
694:
690:
685:
684:
676:
673:
668:
664:
662:
658:
654:
638:
633:
623:
621:
615:
613:
601:
597:
593:
589:
586:
582:
577:
575:
571:
567:
557:
555:
551:
547:
543:
539:
535:
531:
527:
523:
519:
506:
503:
501:
497:
494:
490:
486:
483:
481:
477:
473:
469:
466:
463:
459:
454:
450:
447:
444:
442:
438:
435:
432:
430:
426:
422:
418:
413:
408:
397:
394:
392:
388:
385:
381:
377:
374:
372:
368:
364:
360:
357:
354:
350:
345:
341:
338:
335:
333:
329:
326:
323:
321:
317:
313:
309:
304:
299:
288:
285:
281:
278:
275:
271:
266:
262:
259:
258:
254:
251:
249:
245:
240:
237:
234:
232:
228:
225:
222:
220:
216:
213:
210:
208:
204:
201:
198:
196:
192:
189:
186:
184:
180:
177:
174:
170:
165:
162:
158:
147:
144:
140:
137:
134:
130:
125:
121:
118:
117:
113:
110:
108:
104:
99:
96:
93:
91:
87:
84:
81:
79:
75:
72:
69:
67:
63:
60:
57:
55:
51:
48:
45:
43:
39:
36:
33:
29:
24:
21:
17:
2208:Inflammation
2193:Alloimmunity
2188:Autoimmunity
2173:Immunity vs.
2125:Autoantibody
2023:Superantigen
1934:
1931:Science News
1930:
1878:
1875:PLOS Biology
1874:
1837:
1833:
1800:
1796:
1745:
1741:
1731:
1706:
1702:
1696:
1659:
1655:
1605:
1601:
1591:
1556:
1552:
1542:
1499:
1495:
1457:
1453:
1447:
1404:
1400:
1390:
1347:
1343:
1337:
1302:
1298:
1248:
1244:
1192:
1188:
1138:
1134:
1124:
1087:
1084:PLOS Biology
1083:
1073:
1038:
1034:
1024:
991:
987:
981:
946:
942:
932:
899:
895:
852:
834:urochordates
828:
820:
816:
812:
806:
797:
784:
767:
764:B. belcheri
763:
759:
757:
755:transposon.
752:
748:
742:
738:
734:
728:
722:
709:
697:
665:
629:
616:
578:
563:
517:
515:
255:
114:
2420:Lymphocytes
2331:Lymphocytes
1990:Lymphocytic
1881:(6): e181.
1090:(6): e181.
791:gnathostome
725:transposase
657:nucleotides
639:residues (D
632:amino acids
542:lymphocytes
415:Identifiers
306:Identifiers
277:Swiss-model
167:Identifiers
136:Swiss-model
26:Identifiers
2404:Categories
2372:Substances
2236:Peripheral
2224:Inaction:
2103:Antibodies
2084:Macrophage
1997:complement
1656:Mobile DNA
1195:: 709165.
902:: 233–48.
875:References
825:cnidarians
795:echinoderm
612:covalently
566:vertebrate
468:structures
359:structures
273:Structures
268:Search for
242:Other data
132:Structures
127:Search for
101:Other data
2389:Cytolysin
2379:Cytokines
2226:Tolerance
2175:tolerance
2094:Immunogen
1840:: 70–82.
1748:(1): 47.
1662:(1): 17.
1251:(1): 20.
787:agnathans
727:from the
704:talk page
679:Evolution
626:Structure
600:phosphate
446:IPR004321
337:IPR004321
224:NM_000536
183:NCBI gene
83:NM_000448
42:NCBI gene
2339:Cellular
2183:Immunity
2181:Action:
2164:Paratope
2152:Idiotype
2142:Allotype
2110:Antibody
2064:Mimotope
2028:Allergen
2011:Antigens
2004:Lymphoid
1907:15898832
1862:22044642
1854:15242397
1825:23905210
1817:15242398
1803:: 83–9.
1774:26341882
1723:17707623
1688:32399063
1632:18313399
1583:18562680
1534:16505374
1474:15102370
1439:30971819
1382:11192471
1374:28451741
1329:27293192
1277:25928409
1221:34394111
1165:18313399
1116:15898832
1065:26548953
973:26996199
924:12080467
916:15242409
858:See also
845:system.
804:amphioxi
753:N-RAG-TP
751:and the
739:N-RAG-TP
712:May 2019
596:hydroxyl
588:receptor
560:Function
485:RCSB PDB
441:InterPro
376:RCSB PDB
332:InterPro
287:InterPro
146:InterPro
2384:Opsonin
2363:NK cell
2351:Humoral
2231:Central
2198:Allergy
2147:Isotype
2047:Epitope
2018:Antigen
1951:4010948
1898:1131882
1765:4560925
1679:7204232
1623:2719772
1574:2493399
1525:1450146
1504:Bibcode
1430:6494689
1409:Bibcode
1352:bioRxiv
1320:5017859
1268:4411706
1212:8355894
1156:2719772
1107:1131882
1056:4690471
1016:2360047
996:Bibcode
988:Science
964:5757527
829:Transib
760:Transib
749:Transib
735:Transib
730:Transib
647:, and E
585:antigen
570:antigen
564:In the
550:T cells
546:B cells
434:PF12940
325:PF03089
283:Domains
253:Chr. 11
231:UniProt
142:Domains
112:Chr. 11
90:UniProt
2356:B cell
2344:T cell
2089:B cell
2052:Linear
2040:Hapten
1949:
1905:
1895:
1860:
1852:
1823:
1815:
1772:
1762:
1721:
1686:
1676:
1630:
1620:
1581:
1571:
1532:
1522:
1472:
1437:
1427:
1401:Nature
1380:
1372:
1354:
1327:
1317:
1275:
1265:
1219:
1209:
1163:
1153:
1114:
1104:
1063:
1053:
1014:
971:
961:
922:
914:
637:acidic
500:PDBsum
474:
464:
420:Symbol
391:PDBsum
365:
355:
311:Symbol
236:P55895
219:RefSeq
212:179616
172:Symbol
95:P15918
78:RefSeq
71:179615
31:Symbol
1947:JSTOR
1927:(PDF)
1858:S2CID
1821:S2CID
1378:S2CID
920:S2CID
653:motif
248:Locus
107:Locus
1995:and
1903:PMID
1850:PMID
1813:PMID
1770:PMID
1719:PMID
1684:PMID
1628:PMID
1579:PMID
1530:PMID
1470:PMID
1435:PMID
1370:PMID
1325:PMID
1299:Cell
1273:PMID
1217:PMID
1161:PMID
1112:PMID
1061:PMID
1035:Cell
1012:PMID
969:PMID
912:PMID
779:6b40
548:and
538:RAG2
536:and
534:RAG1
528:and
516:The
493:PDBj
489:PDBe
472:ECOD
462:Pfam
429:Pfam
423:RAG1
384:PDBj
380:PDBe
363:ECOD
353:Pfam
320:Pfam
314:RAG2
207:OMIM
200:9832
195:HGNC
188:5897
176:RAG2
66:OMIM
59:9831
54:HGNC
47:5896
35:RAG1
2317:HLA
2313:MHC
1939:doi
1935:154
1893:PMC
1883:doi
1842:doi
1838:200
1805:doi
1801:200
1760:PMC
1750:doi
1711:doi
1674:PMC
1664:doi
1618:PMC
1610:doi
1606:369
1569:PMC
1561:doi
1520:PMC
1512:doi
1500:103
1462:doi
1425:PMC
1417:doi
1405:569
1362:doi
1315:PMC
1307:doi
1303:166
1263:PMC
1253:doi
1207:PMC
1197:doi
1151:PMC
1143:doi
1139:369
1102:PMC
1092:doi
1051:PMC
1043:doi
1039:163
1004:doi
992:248
959:PMC
951:doi
904:doi
900:200
775:PDB
649:962
645:708
643:, D
641:600
602:(PO
581:DNA
480:PDB
371:PDB
257:p13
116:p13
2406::
2077::
1945:.
1933:.
1929:.
1901:.
1891:.
1877:.
1873:.
1856:.
1848:.
1836:.
1819:.
1811:.
1799:.
1795:.
1768:.
1758:.
1746:10
1744:.
1740:.
1717:.
1707:19
1682:.
1672:.
1660:11
1658:.
1654:.
1640:^
1626:.
1616:.
1604:.
1600:.
1577:.
1567:.
1557:18
1555:.
1551:.
1528:.
1518:.
1510:.
1498:.
1494:.
1482:^
1468:.
1458:25
1456:.
1433:.
1423:.
1415:.
1403:.
1399:.
1376:.
1368:.
1360:.
1348:69
1346:.
1323:.
1313:.
1301:.
1297:.
1285:^
1271:.
1261:.
1249:10
1247:.
1243:.
1229:^
1215:.
1205:.
1193:12
1191:.
1187:.
1173:^
1159:.
1149:.
1137:.
1133:.
1110:.
1100:.
1086:.
1082:.
1059:.
1049:.
1037:.
1033:.
1010:.
1002:.
990:.
967:.
957:.
947:16
945:.
941:.
918:.
910:.
898:.
894:.
882:^
777::
556:.
491:;
487:;
470:/
382:;
378:;
361:/
2315:/
2073:/
1982:e
1975:t
1968:v
1953:.
1941::
1909:.
1885::
1879:3
1864:.
1844::
1827:.
1807::
1776:.
1752::
1725:.
1713::
1690:.
1666::
1634:.
1612::
1585:.
1563::
1536:.
1514::
1506::
1476:.
1464::
1441:.
1419::
1411::
1384:.
1364::
1331:.
1309::
1279:.
1255::
1223:.
1199::
1167:.
1145::
1118:.
1094::
1088:3
1067:.
1045::
1018:.
1006::
998::
975:.
953::
926:.
906::
714:)
710:(
706:.
608:4
604:4
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