957:
40:
506:
A number of CARDs have been shown to play a role in regulating inflammation in response to bacterial and viral pathogens as well as to a variety of endogenous stress signals. Recently, studies on the NLR protein Ipaf-1 have provided insight into how CARDs participate in the immune response. Ipaf-1
584:
Because of their role as regulators of inflammation, constitutive activation of certain CARD-containing proteins, either conferred by mutation or by constant presence of stress signals, has been suggested to play a causative role in a number of inflammatory syndromes. Gain-of-function mutations in
575:
are responsible for phosphorylating and activating IRF3 and IRF7 (Fitzgerald et al., 2003; Hemmi et al., 2004; Matsui et al., 2006). Various studies have also demonstrated the involvement of several other signaling components in virus-induced activation of NF-κB and/or IRF3, including TRAF3, TRAF6,
444:. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs. CARDs are found on a strikingly wide range of proteins, including helicases, kinases, mitochondrial proteins, caspases, and other cytoplasmic factors.
519:
or other stress signals, Ipaf-1 recruits a CARD-containing adapter termed ASC and caspase-1 in unknown stoichiometry via CARD-CARD association. This complex in turn leads to autoproteolytic activation of caspase-1 and subsequent IL-1β and IL-18 maturation.
476:
CARDs were originally characterized based on their involvement in the regulation of caspase activation and apoptosis. The basic six-helix structure of the domain appears to be conserved as far back as the
511:. The primary role of this molecule appears to be regulation of the proteolytic processing of pro-IL-1β and pro-IL-18 into their mature forms via association in a large complex known as the
456:, which features an arrangement of six to seven antiparallel alpha helices with a hydrophobic core and an outer face composed of charged residues. Other motifs in this class include the
489:, the organism in which several components of the apoptotic machinery were first characterized. CARDs are present on a number of proteins that promote apoptosis, primarily
555:
The adaptor protein VISA further activates the inhibitor of nuclear factor kappa-B kinase (IKK)-protein-kinase family members. Although the canonical IKK family members
544:
domains that directly interact with and process the double-stranded viral RNA. This processing makes the CARDs available for interaction with the CARD of IPS-1/MAVS/
385:
175:
576:
TANK, NEMO (IKKg), TRADD, FADD, and RIP (Kawai et al., 2005; Michallet et al., 2008; Oganesyan et al., 2006; Saha et al., 2006; Xu et al., 2005; Zhao et al., 2007).
507:
features an N-terminal CARD, a nucleotide-binding domain, and C-terminal leucine-rich repeats (LRRs), thought to function in a similar fashion to those found in
1284:
532:, a common constituent of a number of viral genomes, including the para- and orthomyxoviridae and rhabdoviridae. Unlike NLRs, these proteins, termed
87:
622:
1481:
774:
742:
321:
111:
1531:
548:/Cardif, a downstream adapter anchored in the mitochondria. Although the interactions between IPS-1 and RIG-I/MDA-5 have been shown
1476:
1491:
1619:
1399:
528:
Recently, a subset of CARD-containing proteins has been shown to participate in recognition of intracellular double-stranded
964:
405:
195:
1354:
1277:
602:
1609:
1543:
598:
1003:"Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment"
341:
131:
1614:
1270:
730:
705:
686:
393:
183:
750:
618:
1187:"Caspase recruitment domain (CARD) as a bi-functional switch of caspase regulation and NF-kappaB signals"
933:
917:
903:
883:
875:
842:
834:
826:
818:
810:
802:
794:
766:
718:
678:
1434:
925:
891:
670:
662:
654:
646:
638:
568:
465:
92:
1113:
Ting JP, Williams KL (2005). "The CATERPILLER family: an ancient family of immune/apoptotic proteins".
858:
850:
782:
630:
389:
179:
334:
124:
346:
136:
1516:
1144:"Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases"
468:(DED), all of which also function primarily in regulation of apoptosis and inflammatory responses.
1583:
1501:
1173:
1032:
790:
508:
429:
698:
586:
1578:
1251:
1208:
1165:
1130:
1101:
1067:
1024:
899:
380:
202:
170:
746:
690:
1568:
1241:
1233:
1198:
1155:
1122:
1093:
1059:
1050:
Hofmann K, Bucher P, Tschopp J (1997). "The CARD domain: a new apoptotic signalling motif".
1014:
854:
773:: receptor-interacting serine-threonine kinase 2 (also called cardiak, RIP2 or RICK kinase)
798:
786:
372:
162:
1506:
1369:
1293:
1246:
1221:
1063:
1019:
1002:
1603:
326:
116:
1177:
1036:
552:, the nature of the complex formed upon viral detection has not been characterized.
302:
68:
1521:
1444:
1429:
1389:
1324:
541:
512:
461:
457:
437:
368:
158:
1237:
1084:
Hiscott J; et al. (2006). "MasterCARD: a priceless link to innate immunity".
1203:
1186:
1097:
947:
314:
80:
1588:
1573:
1496:
1486:
1466:
1461:
1456:
1419:
1374:
1349:
1334:
1329:
1314:
722:
545:
1160:
1143:
1126:
1563:
1558:
1553:
1538:
1526:
1511:
1451:
1424:
1414:
1409:
1404:
1394:
1364:
1359:
1344:
1339:
1319:
1309:
682:
674:
637:: apoptosis-related cysteine peptidase (interleukin 1, beta, convertase; ICE)
453:
1548:
1471:
1384:
1379:
1304:
666:
658:
650:
642:
634:
590:
441:
1255:
1212:
1169:
1134:
1105:
17:
1071:
1028:
589:. Activating mutations in at least two related PYD-containing proteins,
330:
120:
39:
564:
309:
75:
490:
433:
99:
789:: Bcl10-interacting CARD protein or BinCARD, also called chromosome 9
262:
256:
250:
244:
238:
232:
226:
220:
214:
208:
929:
874:(CLAN) and Caspase recruitment domain-containing protein 12 (CARD12)
841:: caspase recruitment domain family, member 14 (also called CARMA2)
838:
830:
822:
585:
the intracellular NOD2 protein has been linked to increased risk for
400:
190:
104:
833:: caspase recruitment domain family, member 11 (also called CARMA1)
825:: caspase recruitment domain family, member 10 (also called CARMA3)
694:
1262:
937:
916:: NLR family, pyrin domain containing 1 (previously called NALP1)
913:
907:
895:
865:
846:
814:
806:
778:
770:
762:
754:
734:
714:
709:
MDA-5: Melanoma differentiation-associated protein 5, also called
701:: caspase-1 dominant-negative inhibitor Pseudo-ICE, also known as
626:
614:
594:
572:
533:
943:
921:
887:
879:
702:
560:
556:
537:
362:
297:
152:
63:
1266:
951:
529:
924:: nucleolar protein 3 (apoptosis repressor with CARD domain)
857:: glavaris peptidase activating factor 1 (also called GLAV1)
849:: apoptotic peptidase activating factor 1 (also called CED4)
515:. Upon activation of Ipaf-1 by the intracellular bacterium
737:: Caspase and RIP adapter with death domain also known as
725:: Mitochondrial antiviral-signaling protein also known as
629:
baculoviral IAP repeat-containing 3, also known as C-IAP2
890:: nucleotide-binding oligomerization domain containing 2
882:: nucleotide-binding oligomerization domain containing 1
711:
Interferon-induced helicase C domain-containing protein 1
757:: Retinoic acid-inducible gene 1 protein, also known as
968:
809:/CARDINAL: caspase recruitment domain family, member 8
932:: PYD and CARD containing protein (also called ASC)
862:
IPAF: Ice protease-activating factor, also known as
436:, typically those involved in processes relating to
27:
Interaction motifs found in a wide array of proteins
452:CARDs are a subclass of protein motif known as the
399:
379:
361:
356:
340:
320:
308:
296:
288:
283:
278:
201:
189:
169:
151:
146:
130:
110:
98:
86:
74:
62:
54:
49:
32:
1001:Chou JJ, Matsuo H, Duan H, Wagner G (July 1998).
910:It has also been called NOD27, NOD4, and CLR16.1
621:(IAP) repeat-containing 2, also known as C-IAP1
567:activation, the noncanonical IKK family members
540:, contain twin N-terminal CARDs and C-terminal
817:: caspase recruitment domain family, member 9
801:: caspase recruitment domain family, member 6
1278:
940:analog of caspase-9 in Caenorhabditis elegans
8:
1285:
1271:
1263:
739:RIP-associated protein with a death domain
422:caspase activation and recruitment domains
353:
143:
38:
1245:
1202:
1159:
1018:
993:
872:CARD, LRR, and NACHT-containing protein
685:: apoptosis-related cysteine peptidase
677:: apoptosis-related cysteine peptidase
669:: apoptosis-related cysteine peptidase
661:: apoptosis-related cysteine peptidase
653:: apoptosis-related cysteine peptidase
645:: apoptosis-related cysteine peptidase
1222:"CARD games in apoptosis and immunity"
864:NLR family, card domain containing 4 (
781:: B-cell lymphoma/leukemia 10 protein
279:Caspase recruitment domain, IPS1/RIG-I
275:
29:
727:CARD adapter inducing interferon-beta
7:
1220:Bouchier-Hayes L, Martin SJ (2002).
597:and pyrin/MEFV, have been linked to
563:are essential for virus-triggered
25:
749:: Death adaptor molecule RAIDD-2
955:
902:family CARD domain containing 3
609:List of CARD-containing proteins
497:In the mammalian immune response
1142:Martinon F, Tschopp J (2004).
693:: caspase-1 inhibitor iceberg
493:1,2,4,5,9, and 15 in mammals.
1:
1064:10.1016/S0968-0004(97)01043-8
1020:10.1016/S0092-8674(00)81417-8
357:Available protein structures:
147:Available protein structures:
1204:10.5483/BMBRep.2002.35.1.019
1098:10.1016/j.molmed.2005.12.003
603:familial Mediterranean fever
44:Structure of the RAIDD CARD.
1238:10.1093/embo-reports/kvf139
418:Caspase recruitment domains
1636:
1161:10.1016/j.cell.2004.05.004
1127:10.1016/j.clim.2005.02.007
33:Caspase recruitment domain
1300:
1185:Hong GS, Junk YK (2002).
502:IL-1 and IL-18 processing
432:found in a wide array of
352:
142:
37:
619:Inhibitor of apoptosis
1620:Programmed cell death
946:Autoimmune Regulator
599:Muckle–Wells syndrome
466:death effector domain
969:adding missing items
759:DEAD-box protein 58
524:Antiviral signaling
509:Toll-like receptors
1191:J Biochem Mol Biol
1052:Trends Biochem Sci
967:; you can help by
791:open reading frame
430:interaction motifs
1610:Protein structure
1597:
1596:
985:
984:
900:NOD-like receptor
415:
414:
411:
410:
406:structure summary
274:
273:
270:
269:
196:structure summary
16:(Redirected from
1627:
1287:
1280:
1273:
1264:
1259:
1249:
1216:
1206:
1181:
1163:
1138:
1109:
1076:
1075:
1047:
1041:
1040:
1022:
998:
980:
977:
959:
958:
952:
605:, respectively.
354:
276:
265:
259:
253:
247:
241:
235:
229:
223:
217:
211:
144:
42:
30:
21:
1635:
1634:
1630:
1629:
1628:
1626:
1625:
1624:
1615:Protein domains
1600:
1599:
1598:
1593:
1296:
1294:Protein domains
1291:
1219:
1184:
1141:
1112:
1083:
1080:
1079:
1049:
1048:
1044:
1000:
999:
995:
990:
981:
975:
972:
956:
729:(Cardif/IPS-1)
611:
587:Crohn's disease
582:
526:
504:
499:
474:
450:
261:
255:
249:
243:
237:
231:
225:
219:
213:
207:
45:
28:
23:
22:
15:
12:
11:
5:
1633:
1631:
1623:
1622:
1617:
1612:
1602:
1601:
1595:
1594:
1592:
1591:
1586:
1581:
1576:
1571:
1566:
1561:
1556:
1551:
1546:
1541:
1536:
1535:
1534:
1524:
1519:
1514:
1509:
1504:
1499:
1494:
1489:
1484:
1479:
1474:
1469:
1464:
1459:
1454:
1449:
1448:
1447:
1442:
1437:
1432:
1422:
1417:
1412:
1407:
1402:
1397:
1392:
1387:
1382:
1377:
1372:
1367:
1362:
1357:
1352:
1347:
1342:
1337:
1332:
1327:
1322:
1317:
1312:
1307:
1301:
1298:
1297:
1292:
1290:
1289:
1282:
1275:
1267:
1261:
1260:
1217:
1182:
1139:
1110:
1086:Trends Mol Med
1078:
1077:
1042:
992:
991:
989:
986:
983:
982:
962:
960:
950:
949:
941:
935:
927:
919:
911:
905:
893:
885:
877:
860:
852:
844:
836:
828:
820:
812:
804:
796:
784:
776:
768:
752:
744:
732:
720:
707:
696:
688:
680:
672:
664:
656:
648:
640:
632:
624:
610:
607:
581:
578:
525:
522:
517:S. typhimurium
503:
500:
498:
495:
473:
470:
449:
448:Basic features
446:
413:
412:
409:
408:
403:
397:
396:
383:
377:
376:
366:
359:
358:
350:
349:
344:
338:
337:
324:
318:
317:
312:
306:
305:
300:
294:
293:
290:
286:
285:
281:
280:
272:
271:
268:
267:
205:
199:
198:
193:
187:
186:
173:
167:
166:
156:
149:
148:
140:
139:
134:
128:
127:
114:
108:
107:
102:
96:
95:
90:
84:
83:
78:
72:
71:
66:
60:
59:
56:
52:
51:
47:
46:
43:
35:
34:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
1632:
1621:
1618:
1616:
1613:
1611:
1608:
1607:
1605:
1590:
1587:
1585:
1582:
1580:
1577:
1575:
1572:
1570:
1567:
1565:
1562:
1560:
1557:
1555:
1552:
1550:
1547:
1545:
1542:
1540:
1537:
1533:
1530:
1529:
1528:
1525:
1523:
1520:
1518:
1515:
1513:
1510:
1508:
1505:
1503:
1500:
1498:
1495:
1493:
1490:
1488:
1485:
1483:
1480:
1478:
1475:
1473:
1470:
1468:
1465:
1463:
1460:
1458:
1455:
1453:
1450:
1446:
1443:
1441:
1438:
1436:
1433:
1431:
1428:
1427:
1426:
1423:
1421:
1418:
1416:
1413:
1411:
1408:
1406:
1403:
1401:
1398:
1396:
1393:
1391:
1388:
1386:
1383:
1381:
1378:
1376:
1373:
1371:
1368:
1366:
1363:
1361:
1358:
1356:
1353:
1351:
1348:
1346:
1343:
1341:
1338:
1336:
1333:
1331:
1328:
1326:
1323:
1321:
1318:
1316:
1313:
1311:
1308:
1306:
1303:
1302:
1299:
1295:
1288:
1283:
1281:
1276:
1274:
1269:
1268:
1265:
1257:
1253:
1248:
1243:
1239:
1235:
1232:(7): 616–21.
1231:
1227:
1223:
1218:
1214:
1210:
1205:
1200:
1196:
1192:
1188:
1183:
1179:
1175:
1171:
1167:
1162:
1157:
1154:(5): 561–74.
1153:
1149:
1145:
1140:
1136:
1132:
1128:
1124:
1120:
1116:
1111:
1107:
1103:
1099:
1095:
1091:
1087:
1082:
1081:
1073:
1069:
1065:
1061:
1057:
1053:
1046:
1043:
1038:
1034:
1030:
1026:
1021:
1016:
1013:(2): 171–80.
1012:
1008:
1004:
997:
994:
987:
979:
970:
966:
963:This list is
961:
954:
953:
948:
945:
942:
939:
936:
934:
931:
928:
926:
923:
920:
918:
915:
912:
909:
906:
904:
901:
897:
894:
892:
889:
886:
884:
881:
878:
876:
873:
869:
867:
861:
859:
856:
853:
851:
848:
845:
843:
840:
837:
835:
832:
829:
827:
824:
821:
819:
816:
813:
811:
808:
805:
803:
800:
797:
795:
793:89 (C9orf89)
792:
788:
785:
783:
780:
777:
775:
772:
769:
767:
764:
760:
756:
753:
751:
748:
745:
743:
740:
736:
733:
731:
728:
724:
721:
719:
716:
712:
708:
706:
704:
700:
697:
695:
692:
689:
687:
684:
681:
679:
676:
673:
671:
668:
665:
663:
660:
657:
655:
652:
649:
647:
644:
641:
639:
636:
633:
631:
628:
625:
623:
620:
616:
613:
612:
608:
606:
604:
600:
596:
592:
588:
579:
577:
574:
570:
566:
562:
558:
553:
551:
547:
543:
539:
535:
531:
523:
521:
518:
514:
510:
501:
496:
494:
492:
488:
484:
480:
471:
469:
467:
463:
459:
455:
447:
445:
443:
439:
435:
431:
427:
423:
419:
407:
404:
402:
398:
395:
391:
387:
384:
382:
378:
374:
370:
367:
364:
360:
355:
351:
348:
345:
343:
339:
336:
332:
328:
325:
323:
319:
316:
313:
311:
307:
304:
301:
299:
295:
291:
287:
282:
277:
264:
258:
252:
246:
240:
234:
228:
222:
216:
210:
206:
204:
200:
197:
194:
192:
188:
185:
181:
177:
174:
172:
168:
164:
160:
157:
154:
150:
145:
141:
138:
135:
133:
129:
126:
122:
118:
115:
113:
109:
106:
103:
101:
97:
94:
91:
89:
85:
82:
79:
77:
73:
70:
67:
65:
61:
57:
53:
48:
41:
36:
31:
19:
1439:
1229:
1225:
1197:(1): 19–23.
1194:
1190:
1151:
1147:
1118:
1115:Clin Immunol
1114:
1089:
1085:
1058:(5): 155–6.
1055:
1051:
1045:
1010:
1006:
996:
973:
871:
863:
758:
738:
726:
710:
617:baculoviral
583:
580:Autoimmunity
554:
549:
542:RNA helicase
527:
516:
513:inflammasome
505:
486:
482:
478:
475:
472:In apoptosis
462:death domain
458:pyrin domain
451:
438:inflammation
425:
421:
417:
416:
1589:zinc finger
1121:(1): 33–7.
1092:(2): 53–6.
976:August 2008
284:Identifiers
50:Identifiers
18:CARD domain
1604:Categories
988:References
965:incomplete
699:Pseudo-ICE
683:caspase-13
675:caspase-12
487:C. elegans
464:(DD), and
454:death fold
369:structures
159:structures
1477:EcoEI_R_C
667:caspase-9
659:caspase-5
651:caspase-4
643:caspase-2
635:caspase-1
591:cryopyrin
485:genes in
442:apoptosis
315:IPR031964
260:,
254:,
248:,
242:,
236:,
230:,
224:,
218:,
212:,
81:IPR001315
1256:12101092
1226:EMBO Rep
1213:16248965
1178:15140093
1170:15163405
1135:15870018
1106:16406812
1037:16499945
741:(RAIDD)
550:in vitro
491:caspases
434:proteins
386:RCSB PDB
310:InterPro
176:RCSB PDB
76:InterPro
1507:Kringle
1400:CGI-121
1370:BTB/POZ
1247:1084193
1072:9175472
1029:9695946
747:RAIDD-2
691:ICEBERG
460:(PYD),
428:), are
347:cd08789
303:PF00619
266:
137:cd01671
105:PS50209
100:PROSITE
93:SM00114
69:PF00619
1254:
1244:
1211:
1176:
1168:
1133:
1104:
1070:
1035:
1027:
930:PYCARD
855:GLAVA1
839:CARD14
831:CARD11
823:CARD10
595:CIAS-1
401:PDBsum
375:
365:
335:SUPFAM
292:CARD_2
289:Symbol
191:PDBsum
165:
155:
125:SUPFAM
55:Symbol
1522:NACHT
1445:Pyrin
1425:Death
1390:Cache
1325:ADF-H
1174:S2CID
1033:S2CID
938:Ced-3
914:NLRP1
908:NLRC5
896:NLRC3
866:NLRC4
847:APAF1
815:CARD9
807:CARD8
799:CARD6
787:BINCA
779:BCL10
771:RIPK2
763:DDX58
755:RIG-I
735:CRADD
715:IFIH1
627:BIRC3
615:BIRC2
573:IKBKE
565:NF-κB
534:RIG-I
483:ced-4
479:ced-3
426:CARDs
420:, or
331:SCOPe
322:SCOP2
121:SCOPe
112:SCOP2
88:SMART
1574:WD40
1569:TRIO
1502:HEAT
1497:FYVE
1492:FGGY
1487:ENTH
1467:DHR2
1462:DHR1
1457:DHHC
1440:CARD
1420:CVHN
1375:BZIP
1350:BESS
1335:ARID
1330:ANTH
1315:ACDC
1252:PMID
1209:PMID
1166:PMID
1148:Cell
1131:PMID
1102:PMID
1068:PMID
1025:PMID
1007:Cell
944:AIRE
922:NOL3
888:NOD2
880:NOD1
723:MAVS
703:COP1
601:and
571:and
569:TBK1
561:IKKb
559:and
557:IKKa
546:VISA
538:MDA5
536:and
481:and
440:and
394:PDBj
390:PDBe
373:ECOD
363:Pfam
327:2lwd
298:Pfam
263:3ygs
257:3crd
251:2ygs
245:2p1h
239:2a5y
233:1z6t
227:1dgn
221:1cy5
215:1cww
209:1c15
184:PDBj
180:PDBe
163:ECOD
153:Pfam
117:3crd
64:Pfam
58:CARD
1584:YTH
1564:SUN
1559:SH3
1554:SH2
1539:PDZ
1532:LOV
1527:PAS
1517:LRR
1512:LIM
1482:EF1
1452:DEP
1435:DED
1415:CUT
1410:CUB
1405:CRM
1395:CBS
1365:BPS
1360:BMC
1355:BIR
1345:BEN
1340:BAR
1320:ACT
1310:ABM
1242:PMC
1234:doi
1199:doi
1156:doi
1152:117
1123:doi
1119:115
1094:doi
1060:doi
1015:doi
971:.
530:RNA
381:PDB
342:CDD
203:PDB
171:PDB
132:CDD
1606::
1579:X8
1549:PX
1544:PH
1472:DM
1430:DD
1385:C2
1380:C1
1305:3H
1250:.
1240:.
1228:.
1224:.
1207:.
1195:35
1193:.
1189:.
1172:.
1164:.
1150:.
1146:.
1129:.
1117:.
1100:.
1090:12
1088:.
1066:.
1056:22
1054:.
1031:.
1023:.
1011:94
1009:.
1005:.
898::
870:,
765:)
717:)
392:;
388:;
371:/
333:/
329:/
182:;
178:;
161:/
123:/
119:/
1286:e
1279:t
1272:v
1258:.
1236::
1230:3
1215:.
1201::
1180:.
1158::
1137:.
1125::
1108:.
1096::
1074:.
1062::
1039:.
1017::
978:)
974:(
868:)
761:(
713:(
593:/
424:(
20:)
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