1107:) can be found almost ubiquitously throughout the animal kingdom. It exerts its biological functions through binding to signalling proteins of the MAPKK level of the MAPK pathway, therefore eliciting a regulatory role in the function of this pathway which mediates proliferation, apoptosis and differentiation in cells. Tribbles-1 is encoded by the trib1 gene, which in humans can be found on chromosome 8 at position 24.13 on the longest arm (q). Recent crystal structures show that Tribbles 1 has an unusual 3D structure, containing a 'broken' C-helix region, a binding site for ubiquitinated substrates such as C/EBPalpha and a key regulatory C-tail region. Like
309:
286:
183:
208:
560:
315:
214:
3887:
3904:
1123:
Tribbles-1 is one of three members of the
Tribbles subfamily, which is a part of the CAMK Ser/Thr protein kinase family, of the protein kinase superfamily. The Tribbles subfamily is one of the pseudokinases, meaning that while expressing putative kinase regions in its structure, it is non-catalytic.
1132:
loop in the function of
Tribbles-1, as the function of Tribbles-1 directly aids in the increase of the amount of it. As positive feedback loops are often seen throughout biology in circumstances that require the alleviation of an external stimulus, the positive feedback loop exhibited by Tribbles-1
1127:
Expression of
Tribbles-1 is highly variable, constantly changing with respect to time and cell-type, which suggests a large amount of regulation that exists in the cell. The protein's primary structure contains a PEST region, indicative of proteins that are highly susceptible to degradation in the
50:
1124:
The
Tribbles subfamily lacks a functional ATP binding pocket, and therefore cannot phosphorylate its substrates; instead, Tribbles proteins function as scaffold proteins, which bind their substrates to localize them to or from their function
1128:
cell; Tribbles-1 plays a role in regulating its own expression by binding to its substrate, which not only produces its function on the MAPK pathway, but also works to protect it from degradation whilst binding. This, in part, creates a
1750:
2035:
1743:
1736:
1943:
322:
221:
1468:
Sung HY, Francis SE, Crossman DC, Kiss-Toth E (April 2006). "Regulation of expression and signalling modulator function of mammalian tribbles is cell-type specific".
2491:
3330:
1794:
3439:
2177:
2064:
818:
799:
144:
2452:
1508:
Tang K, Finley RL, Nie D, Honn KV (March 2000). "Identification of 12-lipoxygenase interaction with cellular proteins by yeast two-hybrid screening".
3425:
2890:
1781:
1763:
3527:
3408:
3978:
3114:
1983:
1210:
3949:
3178:
2153:
1192:
1433:
Foulkes DM, Byrne DP, Bailey FP, Eyers PA (October 2015). "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?".
3968:
3434:
308:
1968:
1026:
3491:
3166:
1704:
1033:
285:
3606:
2423:
2413:
2098:
1326:
3105:
3374:
3046:
2408:
2399:
1179:
1158:
3762:
1175:
1716:
207:
182:
47:
2789:
2286:
2277:
1934:
1880:
3877:
1154:
1977:
124:
321:
220:
1728:
3001:
2819:
2315:
3747:
1619:"Solution structure of human peptidyl prolyl isomerase-like protein 1 and insights into its interaction with SKIP"
314:
213:
3942:
3863:
3850:
3837:
3824:
3811:
3798:
3785:
2991:
2986:
2981:
2971:
2966:
2961:
2951:
2746:
2521:
2117:
3757:
3711:
3654:
3214:
3205:
3156:
1922:
1767:
863:
132:
1230:"Characterization of a phosphoprotein whose mRNA is regulated by the mitogenic pathways in dog thyroid cells"
3659:
3514:
2937:
844:
1654:"Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways"
3680:
3599:
2213:
3752:
3935:
2780:
1228:
Wilkin F, Suarez-Huerta N, Robaye B, Peetermans J, Libert F, Dumont JE, Maenhaut C (September 1997).
196:
111:
3716:
1722:
1710:
1345:"Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease"
984:
933:
3288:
3973:
3649:
3391:
3345:
1308:
156:
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1415:
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1300:
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104:
40:
3919:
1572:
Kiss-Toth E, Bagstaff SM, Sung HY, Jozsa V, Dempsey C, Caunt JC, et al. (October 2004).
1394:"Molecular Mechanism of CCAAT-Enhancer Binding Protein Recruitment by the TRIB1 Pseudokinase"
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231:
1246:
1229:
559:
152:
3742:
3726:
3639:
3070:
2141:
2136:
2131:
376:
1574:"Human tribbles, a protein family controlling mitogen-activated protein kinase cascades"
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1270:
3891:
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3721:
1680:
1653:
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601:
3962:
3685:
3644:
2194:
2126:
588:
1312:
136:
3915:
3634:
3065:
1890:
1539:"SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription"
1104:
394:
173:
160:
3858:
3793:
3629:
3271:
2903:
2843:
2726:
2646:
2370:
1481:
1215:
National Center for
Biotechnology Information, U.S. National Library of Medicine
1197:
National Center for
Biotechnology Information, U.S. National Library of Medicine
734:
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
3886:
1652:
Sung HY, Guan H, Czibula A, King AR, Eder K, Heath E, et al. (June 2007).
477:
3359:
1833:
1410:
1393:
1392:
Murphy JM, Nakatani Y, Jamieson SA, Dai W, Lucet IS, Mace PD (November 2015).
1360:
1286:
293:
190:
140:
3832:
3806:
2320:
1115:, TRIB1 has recently been considered as a potential allosteric drug target.
763:
537:
415:
360:
347:
259:
246:
148:
1689:
1670:
1644:
1635:
1618:
1609:
1590:
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1555:
1538:
1529:
1489:
1454:
1419:
1378:
1304:
1255:
1073:
1068:
2676:
2571:
2566:
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1100:
1057:
908:
889:
1446:
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3308:
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3293:
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3085:
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3055:
2706:
2671:
1910:
1905:
1900:
875:
830:
1617:
Xu C, Zhang J, Huang X, Sun J, Xu Y, Tang Y, et al. (June 2006).
1600:
1521:
81:
77:
73:
69:
3845:
3615:
3565:
3560:
3555:
3550:
3545:
3540:
3535:
3486:
3481:
3476:
3471:
3466:
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3303:
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3229:
3224:
3219:
3193:
3188:
3183:
3171:
3149:
3144:
3036:
3011:
2686:
2511:
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2501:
2496:
2481:
2325:
2262:
2257:
2252:
2228:
2054:
2049:
2023:
2018:
2013:
2003:
1998:
1988:
1828:
1759:
1041:
785:
3903:
704:
negative regulation of lipopolysaccharide-mediated signaling pathway
1271:"Tribbles: novel regulators of cell function; evolutionary aspects"
3819:
3461:
3454:
3364:
3261:
3161:
3139:
3134:
3129:
3124:
3119:
3031:
3026:
3021:
3016:
3006:
2976:
2956:
2833:
2828:
2809:
2804:
2794:
2770:
2765:
2760:
2736:
2731:
2721:
2716:
2701:
2681:
2666:
2661:
2656:
2636:
2631:
2621:
2616:
2611:
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2601:
2591:
2586:
2581:
2576:
2556:
2551:
2546:
2541:
2536:
2531:
2516:
2466:
2461:
2355:
2350:
2345:
2340:
2335:
2330:
2291:
2223:
2218:
2167:
2162:
2088:
2083:
2078:
2044:
2036:
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase
1838:
1823:
1818:
1813:
1808:
1803:
1112:
1108:
748:
744:
3911:
3354:
3281:
3276:
3266:
3239:
2996:
2946:
2927:
2922:
2917:
2912:
2867:
2862:
2857:
2852:
2799:
2755:
2696:
2691:
2641:
2626:
2596:
2526:
2442:
2437:
2432:
2365:
2267:
2208:
2203:
2107:
2073:
1958:
1953:
1948:
1917:
1885:
1873:
1868:
1863:
1853:
1848:
1096:
694:
negative regulation of DNA-binding transcription factor activity
568:
128:
115:, C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1, tribbles pseudokinase 1
3588:
3512:
2888:
1779:
1732:
3323:
1858:
1843:
1133:
suggests that it plays a functional role in cell response.
3584:
384:
3923:
674:
negative regulation of smooth muscle cell proliferation
3875:
549:
1327:"Entrez Gene: TRIB1 tribbles homolog 1 (Drosophila)"
3771:
3735:
3704:
3673:
3622:
3526:
3424:
3407:
3390:
3373:
3344:
3204:
3104:
3045:
2936:
2902:
2842:
2818:
2779:
2745:
2451:
2422:
2398:
2379:
2300:
2276:
2237:
2193:
2176:
2152:
2116:
2097:
2063:
2034:
1967:
1933:
1793:
1002:
977:
951:
926:
689:
negative regulation of smooth muscle cell migration
1171:
1169:
1167:
1150:
1148:
1146:
724:positive regulation of eosinophil differentiation
699:negative regulation of neutrophil differentiation
684:positive regulation of macrophage differentiation
331:
230:
607:ubiquitin-protein transferase regulator activity
1269:Hegedus Z, Czibula A, Kiss-Toth E (July 2006).
627:mitogen-activated protein kinase kinase binding
16:Protein-coding gene in the species Homo sapiens
1338:
1336:
1176:GRCm38: Ensembl release 89: ENSMUSG00000032501
679:negative regulation of protein kinase activity
3943:
3600:
1795:Non-specific serine/threonine protein kinases
1744:
8:
1343:Eyers PA, Keeshan K, Kannan N (April 2017).
1155:GRCh38: Ensembl release 89: ENSG00000173334
3950:
3936:
3607:
3593:
3585:
3523:
3509:
2899:
2885:
2178:Goodpasture-antigen-binding protein kinase
1790:
1776:
1751:
1737:
1729:
759:
584:
454:Skeletal muscle tissue of rectus abdominis
372:
271:
168:
58:
2891:Serine/threonine-specific protein kinases
2065:(isocitrate dehydrogenase (NADP+)) kinase
1782:Serine/threonine-specific protein kinases
1764:Serine/threonine-specific protein kinases
1679:
1669:
1634:
1599:
1589:
1554:
1537:Wu M, Xu LG, Zhai Z, Shu HB (July 2003).
1409:
1368:
1294:
1245:
3426:Receptor protein serine/threonine kinase
3882:
3409:Low-density-lipoprotein receptor kinase
1142:
1247:10.1111/j.1432-1033.1997.t01-1-00660.x
18:
2154:Fas-activated serine/threonine kinase
336:
297:
292:
235:
194:
189:
7:
3900:
3898:
3435:Bone morphogenetic protein receptors
1275:Cellular and Molecular Life Sciences
1969:Dephospho-(reductase kinase) kinase
1658:The Journal of Biological Chemistry
1623:The Journal of Biological Chemistry
1578:The Journal of Biological Chemistry
1543:The Journal of Biological Chemistry
3922:. You can help Knowledge (XXG) by
2424:G-protein coupled receptor kinases
999:
974:
948:
923:
899:
880:
854:
835:
809:
790:
554:
472:
410:
389:
14:
2414:Beta adrenergic receptor kinase-2
2099:(tyrosine 3-monooxygenase) kinase
1092:that in humans is encoded by the
729:regulation of MAP kinase activity
612:protein kinase inhibitor activity
3902:
3885:
3106:Mitogen-activated protein kinase
1435:Biochemical Society Transactions
1234:European Journal of Biochemistry
637:ubiquitin protein ligase binding
558:
320:
313:
307:
284:
219:
212:
206:
181:
3492:Anti-MĂĽllerian hormone receptor
3375:(acetyl-CoA carboxylase) kinase
3047:(RNA-polymerase)-subunit kinase
2409:Beta adrenergic receptor kinase
2400:Beta adrenergic receptor kinase
3115:Extracellular signal-regulated
1103:of this protein pseudokinase (
719:response to lipopolysaccharide
569:More reference expression data
538:More reference expression data
1:
3979:Human chromosome 8 gene stubs
3179:P38 mitogen-activated protein
2278:cGMP-dependent protein kinase
2239:cAMP-dependent protein kinase
1935:Pyruvate dehydrogenase kinase
1881:Ataxia telangiectasia mutated
305:
204:
1978:AMP-activated protein kinase
617:transcription factor binding
3969:Genes on human chromosome 8
2893:(EC 2.7.11.21-EC 2.7.11.30)
1709:human gene location in the
1482:10.1016/j.imlet.2005.11.010
3995:
3897:
2820:Elongation factor 2 kinase
1784:(EC 2.7.11.1-EC 2.7.11.20)
1721:human gene details in the
492:retinal pigment epithelium
3763:Michaelis–Menten kinetics
3522:
3508:
3215:MAP kinase kinase kinases
2898:
2884:
2747:Myosin light-chain kinase
2453:Ca2+/calmodulin-dependent
2118:Myosin-heavy-chain kinase
1789:
1775:
1411:10.1016/j.str.2015.08.017
1361:10.1016/j.tcb.2016.11.002
1287:10.1007/s00018-006-6007-9
1211:"Mouse PubMed Reference:"
1193:"Human PubMed Reference:"
1072:
1067:
1063:
1056:
1040:
1027:Chr 8: 125.43 – 125.44 Mb
1021:
1006:
981:
970:
955:
930:
919:
906:
902:
887:
883:
874:
861:
857:
842:
838:
829:
816:
812:
797:
793:
784:
769:
762:
758:
742:
587:
583:
566:
557:
548:
535:
484:
475:
442:mucosa of paranasal sinus
426:mucosa of urinary bladder
422:
413:
383:
375:
371:
354:
341:
304:
283:
274:
270:
253:
240:
203:
180:
171:
167:
122:
119:
109:
102:
97:
66:
61:
44:
39:
34:
30:
26:
21:
3655:Diffusion-limited enzyme
3515:Dual-specificity kinases
1034:Chr 15: 59.52 – 59.53 Mb
2938:Cyclin-dependent kinase
709:protein phosphorylation
602:protein kinase activity
430:mucosa of sigmoid colon
1671:10.1074/jbc.M610792200
1636:10.1074/jbc.M511155200
1591:10.1074/jbc.M407732200
1556:10.1074/jbc.M209814200
1349:Trends in Cell Biology
3748:Eadie–Hofstee diagram
3681:Allosteric regulation
299:Chromosome 15 (mouse)
3758:Lineweaver–Burk plot
2781:Phosphorylase kinase
197:Chromosome 8 (human)
62:List of PDB id codes
35:Available structures
1723:UCSC Genome Browser
1711:UCSC Genome Browser
1447:10.1042/BST20150109
512:islet of Langerhans
3910:This article on a
3717:Enzyme superfamily
3650:Enzyme promiscuity
3392:Tropomyosin kinase
3346:Tau-protein kinase
1470:Immunology Letters
1086:Tribbles homolog 1
864:ENSMUSG00000032501
667:Biological process
646:Cellular component
595:Molecular function
446:tail of epididymis
3931:
3930:
3873:
3872:
3582:
3581:
3578:
3577:
3574:
3573:
3504:
3503:
3500:
3499:
2880:
2879:
2876:
2875:
2361:Protein kinase N1
2316:Protein kinase Cζ
1522:10.1021/bi992664v
1130:positive feedback
1083:
1082:
1079:
1078:
1052:
1051:
1017:
1016:
996:
995:
966:
965:
945:
944:
915:
914:
896:
895:
870:
869:
851:
850:
825:
824:
806:
805:
754:
753:
579:
578:
575:
574:
544:
543:
531:
530:
469:
468:
367:
366:
266:
265:
161:TRIB1 - orthologs
93:
92:
89:
88:
45:Ortholog search:
3986:
3952:
3945:
3938:
3906:
3899:
3890:
3889:
3881:
3753:Hanes–Woolf plot
3696:Enzyme activator
3691:Enzyme inhibitor
3665:Enzyme catalysis
3609:
3602:
3595:
3586:
3524:
3510:
3157:C-Jun N-terminal
2900:
2886:
2390:Rhodopsin kinase
2381:Rhodopsin kinase
2311:Protein kinase C
2302:Protein kinase C
2287:Protein kinase G
2248:Protein kinase A
1859:Protein kinase B
1791:
1777:
1753:
1746:
1739:
1730:
1693:
1683:
1673:
1664:(25): 18379–87.
1648:
1638:
1613:
1603:
1593:
1568:
1558:
1533:
1494:
1493:
1465:
1459:
1458:
1430:
1424:
1423:
1413:
1389:
1383:
1382:
1372:
1340:
1331:
1330:
1323:
1317:
1316:
1298:
1266:
1260:
1259:
1249:
1225:
1219:
1218:
1207:
1201:
1200:
1189:
1183:
1173:
1162:
1152:
1065:
1064:
1036:
1029:
1012:
1000:
991:
975:
971:RefSeq (protein)
961:
949:
940:
924:
900:
881:
855:
836:
810:
791:
760:
585:
571:
562:
555:
540:
508:genital tubercle
480:
478:Top expressed in
473:
418:
416:Top expressed in
411:
390:
373:
363:
350:
339:
324:
317:
311:
300:
288:
272:
262:
249:
238:
223:
216:
210:
199:
185:
169:
163:
114:
107:
84:
59:
53:
32:
31:
19:
3994:
3993:
3989:
3988:
3987:
3985:
3984:
3983:
3959:
3958:
3957:
3956:
3896:
3884:
3876:
3874:
3869:
3781:Oxidoreductases
3767:
3743:Enzyme kinetics
3731:
3727:List of enzymes
3700:
3669:
3640:Catalytic triad
3618:
3613:
3583:
3570:
3518:
3496:
3420:
3403:
3386:
3369:
3340:
3200:
3100:
3071:P70-S6 Kinase 1
3041:
2932:
2894:
2872:
2838:
2814:
2775:
2741:
2447:
2418:
2394:
2375:
2296:
2272:
2233:
2189:
2172:
2148:
2142:Aurora C kinase
2137:Aurora B kinase
2132:Aurora A kinase
2112:
2093:
2059:
2030:
1963:
1929:
1785:
1771:
1757:
1701:
1696:
1651:
1629:(23): 15900–8.
1616:
1584:(41): 42703–8.
1571:
1549:(29): 27072–9.
1536:
1516:(12): 3185–91.
1507:
1503:
1501:Further reading
1498:
1497:
1467:
1466:
1462:
1441:(5): 1095–103.
1432:
1431:
1427:
1404:(11): 2111–21.
1391:
1390:
1386:
1342:
1341:
1334:
1325:
1324:
1320:
1281:(14): 1632–41.
1268:
1267:
1263:
1227:
1226:
1222:
1209:
1208:
1204:
1191:
1190:
1186:
1174:
1165:
1153:
1144:
1139:
1121:
1074:View/Edit Mouse
1069:View/Edit Human
1032:
1025:
1022:Location (UCSC)
1008:
987:
983:
957:
936:
932:
845:ENSG00000173334
738:
662:
641:
622:protein binding
567:
536:
527:
522:
518:
514:
510:
506:
502:
498:
494:
490:
476:
465:
460:
456:
452:
448:
444:
440:
436:
434:visceral pleura
432:
428:
414:
358:
345:
337:
327:
326:
325:
318:
298:
275:Gene location (
257:
244:
236:
226:
225:
224:
217:
195:
172:Gene location (
123:
110:
103:
68:
46:
17:
12:
11:
5:
3992:
3990:
3982:
3981:
3976:
3971:
3961:
3960:
3955:
3954:
3947:
3940:
3932:
3929:
3928:
3907:
3895:
3894:
3871:
3870:
3868:
3867:
3854:
3841:
3828:
3815:
3802:
3789:
3775:
3773:
3769:
3768:
3766:
3765:
3760:
3755:
3750:
3745:
3739:
3737:
3733:
3732:
3730:
3729:
3724:
3719:
3714:
3708:
3706:
3705:Classification
3702:
3701:
3699:
3698:
3693:
3688:
3683:
3677:
3675:
3671:
3670:
3668:
3667:
3662:
3657:
3652:
3647:
3642:
3637:
3632:
3626:
3624:
3620:
3619:
3614:
3612:
3611:
3604:
3597:
3589:
3580:
3579:
3576:
3575:
3572:
3571:
3569:
3568:
3563:
3558:
3553:
3548:
3543:
3538:
3532:
3530:
3520:
3519:
3513:
3506:
3505:
3502:
3501:
3498:
3497:
3495:
3494:
3489:
3484:
3479:
3474:
3469:
3464:
3459:
3458:
3457:
3452:
3447:
3442:
3431:
3429:
3428:(EC 2.7.11.30)
3422:
3421:
3419:
3418:
3414:
3412:
3411:(EC 2.7.11.29)
3405:
3404:
3402:
3401:
3397:
3395:
3394:(EC 2.7.11.28)
3388:
3387:
3385:
3384:
3380:
3378:
3377:(EC 2.7.11.27)
3371:
3370:
3368:
3367:
3362:
3357:
3351:
3349:
3348:(EC 2.7.11.26)
3342:
3341:
3339:
3338:
3333:
3328:
3327:
3326:
3321:
3316:
3311:
3306:
3301:
3296:
3286:
3285:
3284:
3279:
3274:
3269:
3259:
3258:
3257:
3252:
3247:
3242:
3237:
3232:
3227:
3222:
3211:
3209:
3208:(EC 2.7.11.25)
3202:
3201:
3199:
3198:
3197:
3196:
3191:
3186:
3176:
3175:
3174:
3169:
3164:
3154:
3153:
3152:
3147:
3142:
3137:
3132:
3127:
3122:
3111:
3109:
3108:(EC 2.7.11.24)
3102:
3101:
3099:
3098:
3093:
3088:
3083:
3078:
3073:
3068:
3063:
3058:
3052:
3050:
3049:(EC 2.7.11.23)
3043:
3042:
3040:
3039:
3034:
3029:
3024:
3019:
3014:
3009:
3004:
2999:
2994:
2989:
2984:
2979:
2974:
2969:
2964:
2959:
2954:
2949:
2943:
2941:
2940:(EC 2.7.11.22)
2934:
2933:
2931:
2930:
2925:
2920:
2915:
2909:
2907:
2906:(EC 2.7.11.21)
2896:
2895:
2889:
2882:
2881:
2878:
2877:
2874:
2873:
2871:
2870:
2865:
2860:
2855:
2849:
2847:
2846:(EC 2.7.11.21)
2840:
2839:
2837:
2836:
2831:
2825:
2823:
2822:(EC 2.7.11.20)
2816:
2815:
2813:
2812:
2807:
2802:
2797:
2792:
2786:
2784:
2783:(EC 2.7.11.19)
2777:
2776:
2774:
2773:
2768:
2763:
2758:
2752:
2750:
2749:(EC 2.7.11.18)
2743:
2742:
2740:
2739:
2734:
2729:
2724:
2719:
2714:
2709:
2704:
2699:
2694:
2689:
2684:
2679:
2674:
2669:
2664:
2659:
2654:
2649:
2644:
2639:
2634:
2629:
2624:
2619:
2614:
2609:
2604:
2599:
2594:
2589:
2584:
2579:
2574:
2569:
2564:
2559:
2554:
2549:
2544:
2539:
2534:
2529:
2524:
2519:
2514:
2509:
2504:
2499:
2494:
2489:
2484:
2479:
2474:
2469:
2464:
2458:
2456:
2455:(EC 2.7.11.17)
2449:
2448:
2446:
2445:
2440:
2435:
2429:
2427:
2426:(EC 2.7.11.16)
2420:
2419:
2417:
2416:
2411:
2405:
2403:
2402:(EC 2.7.11.15)
2396:
2395:
2393:
2392:
2386:
2384:
2383:(EC 2.7.11.14)
2377:
2376:
2374:
2373:
2368:
2363:
2358:
2353:
2348:
2343:
2338:
2333:
2328:
2323:
2318:
2313:
2307:
2305:
2304:(EC 2.7.11.13)
2298:
2297:
2295:
2294:
2289:
2283:
2281:
2280:(EC 2.7.11.12)
2274:
2273:
2271:
2270:
2265:
2260:
2255:
2250:
2244:
2242:
2241:(EC 2.7.11.11)
2235:
2234:
2232:
2231:
2226:
2221:
2216:
2211:
2206:
2200:
2198:
2197:(EC 2.7.11.10)
2191:
2190:
2188:
2187:
2183:
2181:
2174:
2173:
2171:
2170:
2165:
2159:
2157:
2150:
2149:
2147:
2146:
2145:
2144:
2139:
2134:
2123:
2121:
2114:
2113:
2111:
2110:
2104:
2102:
2095:
2094:
2092:
2091:
2086:
2081:
2076:
2070:
2068:
2061:
2060:
2058:
2057:
2052:
2047:
2041:
2039:
2032:
2031:
2029:
2028:
2027:
2026:
2021:
2016:
2008:
2007:
2006:
2001:
1993:
1992:
1991:
1986:
1974:
1972:
1965:
1964:
1962:
1961:
1956:
1951:
1946:
1940:
1938:
1931:
1930:
1928:
1927:
1926:
1925:
1915:
1914:
1913:
1908:
1903:
1898:
1888:
1883:
1878:
1877:
1876:
1871:
1866:
1856:
1851:
1846:
1841:
1836:
1831:
1826:
1821:
1816:
1811:
1806:
1800:
1798:
1787:
1786:
1780:
1773:
1772:
1758:
1756:
1755:
1748:
1741:
1733:
1727:
1726:
1714:
1700:
1699:External links
1697:
1695:
1694:
1649:
1614:
1569:
1534:
1504:
1502:
1499:
1496:
1495:
1476:(1–2): 171–7.
1460:
1425:
1384:
1355:(4): 284–298.
1332:
1318:
1261:
1220:
1202:
1184:
1163:
1141:
1140:
1138:
1135:
1120:
1117:
1090:protein kinase
1081:
1080:
1077:
1076:
1071:
1061:
1060:
1054:
1053:
1050:
1049:
1047:
1045:
1038:
1037:
1030:
1023:
1019:
1018:
1015:
1014:
1004:
1003:
997:
994:
993:
979:
978:
972:
968:
967:
964:
963:
953:
952:
946:
943:
942:
928:
927:
921:
917:
916:
913:
912:
904:
903:
897:
894:
893:
885:
884:
878:
872:
871:
868:
867:
859:
858:
852:
849:
848:
840:
839:
833:
827:
826:
823:
822:
814:
813:
807:
804:
803:
795:
794:
788:
782:
781:
776:
771:
767:
766:
756:
755:
752:
751:
740:
739:
737:
736:
731:
726:
721:
716:
711:
706:
701:
696:
691:
686:
681:
676:
670:
668:
664:
663:
661:
660:
655:
649:
647:
643:
642:
640:
639:
634:
629:
624:
619:
614:
609:
604:
598:
596:
592:
591:
581:
580:
577:
576:
573:
572:
564:
563:
552:
546:
545:
542:
541:
533:
532:
529:
528:
526:
525:
521:
517:
513:
509:
505:
504:tail of embryo
501:
500:lacrimal gland
497:
493:
489:
485:
482:
481:
470:
467:
466:
464:
463:
459:
455:
451:
447:
443:
439:
435:
431:
427:
423:
420:
419:
407:
406:
398:
387:
381:
380:
377:RNA expression
369:
368:
365:
364:
356:
352:
351:
343:
340:
335:
329:
328:
319:
312:
306:
302:
301:
296:
290:
289:
281:
280:
268:
267:
264:
263:
255:
251:
250:
242:
239:
234:
228:
227:
218:
211:
205:
201:
200:
193:
187:
186:
178:
177:
165:
164:
121:
117:
116:
108:
100:
99:
95:
94:
91:
90:
87:
86:
64:
63:
55:
54:
43:
37:
36:
28:
27:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
3991:
3980:
3977:
3975:
3972:
3970:
3967:
3966:
3964:
3953:
3948:
3946:
3941:
3939:
3934:
3933:
3927:
3925:
3921:
3917:
3913:
3908:
3905:
3901:
3893:
3888:
3883:
3879:
3865:
3861:
3860:
3855:
3852:
3848:
3847:
3842:
3839:
3835:
3834:
3829:
3826:
3822:
3821:
3816:
3813:
3809:
3808:
3803:
3800:
3796:
3795:
3790:
3787:
3783:
3782:
3777:
3776:
3774:
3770:
3764:
3761:
3759:
3756:
3754:
3751:
3749:
3746:
3744:
3741:
3740:
3738:
3734:
3728:
3725:
3723:
3722:Enzyme family
3720:
3718:
3715:
3713:
3710:
3709:
3707:
3703:
3697:
3694:
3692:
3689:
3687:
3686:Cooperativity
3684:
3682:
3679:
3678:
3676:
3672:
3666:
3663:
3661:
3658:
3656:
3653:
3651:
3648:
3646:
3645:Oxyanion hole
3643:
3641:
3638:
3636:
3633:
3631:
3628:
3627:
3625:
3621:
3617:
3610:
3605:
3603:
3598:
3596:
3591:
3590:
3587:
3567:
3564:
3562:
3559:
3557:
3554:
3552:
3549:
3547:
3544:
3542:
3539:
3537:
3534:
3533:
3531:
3529:
3525:
3521:
3516:
3511:
3507:
3493:
3490:
3488:
3485:
3483:
3480:
3478:
3475:
3473:
3470:
3468:
3465:
3463:
3460:
3456:
3453:
3451:
3448:
3446:
3443:
3441:
3438:
3437:
3436:
3433:
3432:
3430:
3427:
3423:
3416:
3415:
3413:
3410:
3406:
3399:
3398:
3396:
3393:
3389:
3382:
3381:
3379:
3376:
3372:
3366:
3363:
3361:
3358:
3356:
3353:
3352:
3350:
3347:
3343:
3337:
3334:
3332:
3329:
3325:
3322:
3320:
3317:
3315:
3312:
3310:
3307:
3305:
3302:
3300:
3297:
3295:
3292:
3291:
3290:
3287:
3283:
3280:
3278:
3275:
3273:
3270:
3268:
3265:
3264:
3263:
3260:
3256:
3253:
3251:
3248:
3246:
3243:
3241:
3238:
3236:
3233:
3231:
3228:
3226:
3223:
3221:
3218:
3217:
3216:
3213:
3212:
3210:
3207:
3203:
3195:
3192:
3190:
3187:
3185:
3182:
3181:
3180:
3177:
3173:
3170:
3168:
3165:
3163:
3160:
3159:
3158:
3155:
3151:
3148:
3146:
3143:
3141:
3138:
3136:
3133:
3131:
3128:
3126:
3123:
3121:
3118:
3117:
3116:
3113:
3112:
3110:
3107:
3103:
3097:
3094:
3092:
3089:
3087:
3084:
3082:
3079:
3077:
3074:
3072:
3069:
3067:
3064:
3062:
3059:
3057:
3054:
3053:
3051:
3048:
3044:
3038:
3035:
3033:
3030:
3028:
3025:
3023:
3020:
3018:
3015:
3013:
3010:
3008:
3005:
3003:
3000:
2998:
2995:
2993:
2990:
2988:
2985:
2983:
2980:
2978:
2975:
2973:
2970:
2968:
2965:
2963:
2960:
2958:
2955:
2953:
2950:
2948:
2945:
2944:
2942:
2939:
2935:
2929:
2926:
2924:
2921:
2919:
2916:
2914:
2911:
2910:
2908:
2905:
2901:
2897:
2892:
2887:
2883:
2869:
2866:
2864:
2861:
2859:
2856:
2854:
2851:
2850:
2848:
2845:
2841:
2835:
2832:
2830:
2827:
2826:
2824:
2821:
2817:
2811:
2808:
2806:
2803:
2801:
2798:
2796:
2793:
2791:
2788:
2787:
2785:
2782:
2778:
2772:
2769:
2767:
2764:
2762:
2759:
2757:
2754:
2753:
2751:
2748:
2744:
2738:
2735:
2733:
2730:
2728:
2725:
2723:
2720:
2718:
2715:
2713:
2710:
2708:
2705:
2703:
2700:
2698:
2695:
2693:
2690:
2688:
2685:
2683:
2680:
2678:
2675:
2673:
2670:
2668:
2665:
2663:
2660:
2658:
2655:
2653:
2650:
2648:
2645:
2643:
2640:
2638:
2635:
2633:
2630:
2628:
2625:
2623:
2620:
2618:
2615:
2613:
2610:
2608:
2605:
2603:
2600:
2598:
2595:
2593:
2590:
2588:
2585:
2583:
2580:
2578:
2575:
2573:
2570:
2568:
2565:
2563:
2560:
2558:
2555:
2553:
2550:
2548:
2545:
2543:
2540:
2538:
2535:
2533:
2530:
2528:
2525:
2523:
2520:
2518:
2515:
2513:
2510:
2508:
2505:
2503:
2500:
2498:
2495:
2493:
2490:
2488:
2485:
2483:
2480:
2478:
2475:
2473:
2470:
2468:
2465:
2463:
2460:
2459:
2457:
2454:
2450:
2444:
2441:
2439:
2436:
2434:
2431:
2430:
2428:
2425:
2421:
2415:
2412:
2410:
2407:
2406:
2404:
2401:
2397:
2391:
2388:
2387:
2385:
2382:
2378:
2372:
2369:
2367:
2364:
2362:
2359:
2357:
2354:
2352:
2349:
2347:
2344:
2342:
2339:
2337:
2334:
2332:
2329:
2327:
2324:
2322:
2319:
2317:
2314:
2312:
2309:
2308:
2306:
2303:
2299:
2293:
2290:
2288:
2285:
2284:
2282:
2279:
2275:
2269:
2266:
2264:
2261:
2259:
2256:
2254:
2251:
2249:
2246:
2245:
2243:
2240:
2236:
2230:
2227:
2225:
2222:
2220:
2217:
2215:
2212:
2210:
2207:
2205:
2202:
2201:
2199:
2196:
2192:
2185:
2184:
2182:
2180:(EC 2.7.11.9)
2179:
2175:
2169:
2166:
2164:
2161:
2160:
2158:
2156:(EC 2.7.11.8)
2155:
2151:
2143:
2140:
2138:
2135:
2133:
2130:
2129:
2128:
2127:Aurora kinase
2125:
2124:
2122:
2120:(EC 2.7.11.7)
2119:
2115:
2109:
2106:
2105:
2103:
2101:(EC 2.7.11.6)
2100:
2096:
2090:
2087:
2085:
2082:
2080:
2077:
2075:
2072:
2071:
2069:
2067:(EC 2.7.11.5)
2066:
2062:
2056:
2053:
2051:
2048:
2046:
2043:
2042:
2040:
2038:(EC 2.7.11.4)
2037:
2033:
2025:
2022:
2020:
2017:
2015:
2012:
2011:
2009:
2005:
2002:
2000:
1997:
1996:
1994:
1990:
1987:
1985:
1982:
1981:
1979:
1976:
1975:
1973:
1971:(EC 2.7.11.3)
1970:
1966:
1960:
1957:
1955:
1952:
1950:
1947:
1945:
1942:
1941:
1939:
1937:(EC 2.7.11.2)
1936:
1932:
1924:
1921:
1920:
1919:
1916:
1912:
1909:
1907:
1904:
1902:
1899:
1897:
1894:
1893:
1892:
1891:EIF-2 kinases
1889:
1887:
1884:
1882:
1879:
1875:
1872:
1870:
1867:
1865:
1862:
1861:
1860:
1857:
1855:
1852:
1850:
1847:
1845:
1842:
1840:
1837:
1835:
1832:
1830:
1827:
1825:
1822:
1820:
1817:
1815:
1812:
1810:
1807:
1805:
1802:
1801:
1799:
1797:(EC 2.7.11.1)
1796:
1792:
1788:
1783:
1778:
1774:
1769:
1765:
1761:
1754:
1749:
1747:
1742:
1740:
1735:
1734:
1731:
1724:
1720:
1719:
1715:
1712:
1708:
1707:
1703:
1702:
1698:
1691:
1687:
1682:
1677:
1672:
1667:
1663:
1659:
1655:
1650:
1646:
1642:
1637:
1632:
1628:
1624:
1620:
1615:
1611:
1607:
1602:
1597:
1592:
1587:
1583:
1579:
1575:
1570:
1566:
1562:
1557:
1552:
1548:
1544:
1540:
1535:
1531:
1527:
1523:
1519:
1515:
1511:
1506:
1505:
1500:
1491:
1487:
1483:
1479:
1475:
1471:
1464:
1461:
1456:
1452:
1448:
1444:
1440:
1436:
1429:
1426:
1421:
1417:
1412:
1407:
1403:
1399:
1395:
1388:
1385:
1380:
1376:
1371:
1366:
1362:
1358:
1354:
1350:
1346:
1339:
1337:
1333:
1328:
1322:
1319:
1314:
1310:
1306:
1302:
1297:
1292:
1288:
1284:
1280:
1276:
1272:
1265:
1262:
1257:
1253:
1248:
1243:
1239:
1235:
1231:
1224:
1221:
1216:
1212:
1206:
1203:
1198:
1194:
1188:
1185:
1181:
1177:
1172:
1170:
1168:
1164:
1160:
1156:
1151:
1149:
1147:
1143:
1136:
1134:
1131:
1125:
1118:
1116:
1114:
1110:
1106:
1102:
1098:
1095:
1091:
1087:
1075:
1070:
1066:
1062:
1059:
1055:
1048:
1046:
1043:
1039:
1035:
1031:
1028:
1024:
1020:
1013:
1011:
1005:
1001:
998:
992:
990:
986:
980:
976:
973:
969:
962:
960:
954:
950:
947:
941:
939:
935:
929:
925:
922:
920:RefSeq (mRNA)
918:
911:
910:
905:
901:
898:
892:
891:
886:
882:
879:
877:
873:
866:
865:
860:
856:
853:
847:
846:
841:
837:
834:
832:
828:
821:
820:
815:
811:
808:
802:
801:
796:
792:
789:
787:
783:
780:
777:
775:
772:
768:
765:
761:
757:
750:
746:
741:
735:
732:
730:
727:
725:
722:
720:
717:
715:
712:
710:
707:
705:
702:
700:
697:
695:
692:
690:
687:
685:
682:
680:
677:
675:
672:
671:
669:
666:
665:
659:
656:
654:
651:
650:
648:
645:
644:
638:
635:
633:
630:
628:
625:
623:
620:
618:
615:
613:
610:
608:
605:
603:
600:
599:
597:
594:
593:
590:
589:Gene ontology
586:
582:
570:
565:
561:
556:
553:
551:
547:
539:
534:
523:
519:
515:
511:
507:
503:
499:
496:parotid gland
495:
491:
487:
486:
483:
479:
474:
471:
462:thyroid gland
461:
458:kidney tubule
457:
453:
450:parotid gland
449:
445:
441:
437:
433:
429:
425:
424:
421:
417:
412:
409:
408:
405:
403:
399:
397:
396:
392:
391:
388:
386:
382:
378:
374:
370:
362:
357:
353:
349:
344:
338:15|15 D1
334:
330:
323:
316:
310:
303:
295:
291:
287:
282:
278:
273:
269:
261:
256:
252:
248:
243:
233:
229:
222:
215:
209:
202:
198:
192:
188:
184:
179:
175:
170:
166:
162:
158:
154:
150:
146:
142:
138:
134:
130:
126:
118:
113:
106:
101:
96:
85:
83:
79:
75:
71:
65:
60:
57:
56:
52:
49:
42:
38:
33:
29:
25:
20:
3924:expanding it
3916:chromosome 8
3909:
3859:Translocases
3856:
3843:
3830:
3817:
3804:
3794:Transferases
3791:
3778:
3635:Binding site
3066:P70S6 kinase
2711:
1717:
1705:
1661:
1657:
1626:
1622:
1581:
1577:
1546:
1542:
1513:
1510:Biochemistry
1509:
1473:
1469:
1463:
1438:
1434:
1428:
1401:
1397:
1387:
1352:
1348:
1321:
1278:
1274:
1264:
1240:(3): 660–8.
1237:
1233:
1223:
1214:
1205:
1196:
1187:
1126:
1122:
1105:pseudoenzyme
1093:
1085:
1084:
1007:
985:NP_001269914
982:
956:
934:NM_001282985
931:
907:
888:
862:
843:
817:
798:
778:
773:
400:
393:
258:125,438,403
245:125,430,358
120:External IDs
67:
3630:Active site
3517:(EC 2.7.12)
2904:Polo kinase
2844:Polo kinase
714:JNK cascade
632:ATP binding
488:granulocyte
438:gallbladder
359:59,528,948
346:59,520,199
98:Identifiers
3963:Categories
3833:Isomerases
3807:Hydrolases
3674:Regulation
2195:IÎşB kinase
1770:2.7.11-12)
1601:2262/33449
1182:, May 2017
1161:, May 2017
1137:References
516:left colon
404:(ortholog)
141:HomoloGene
3974:EC 2.7.11
3914:on human
3712:EC number
2321:PKC alpha
1398:Structure
1101:Orthologs
1010:NP_653132
989:NP_079471
959:NM_144549
938:NM_025195
764:Orthologs
653:cytoplasm
149:GeneCards
3736:Kinetics
3660:Cofactor
3623:Activity
2677:KIAA0999
2572:MAPKAPK5
2567:MAPKAPK3
2562:MAPKAPK2
1690:17452330
1645:16595688
1610:15299019
1565:12736262
1530:10727209
1490:16364454
1455:26517930
1420:26455797
1379:27908682
1313:24556931
1305:16715410
1296:11136108
1178:–
1157:–
1119:Function
1058:Wikidata
743:Sources:
3892:Biology
3846:Ligases
3616:Enzymes
3336:MAP3K14
3314:MAP3K11
3309:MAP3K10
3299:MAP3K13
3294:MAP3K12
3096:RPS6KC1
3091:RPS6KA1
3086:RPS6KA3
3081:RPS6KA2
3076:RPS6KB2
3061:RPS6KA4
3056:RPS6KA5
2707:Kalirin
2672:SNF1LK2
1911:EIF2AK4
1906:EIF2AK3
1760:Kinases
1681:2366084
1370:5382568
1256:9342215
1180:Ensembl
1159:Ensembl
876:UniProt
831:Ensembl
770:Species
749:QuickGO
658:nucleus
379:pattern
237:8q24.13
137:2443397
105:Aliases
3878:Portal
3820:Lyases
3566:MAP2K7
3561:MAP2K6
3556:MAP2K5
3551:MAP2K4
3546:MAP2K3
3541:MAP2K2
3536:MAP2K1
3487:ACVRL1
3482:ACVR2B
3477:ACVR2A
3472:ACVR1C
3467:ACVR1B
3450:BMPR1B
3445:BMPR1A
3319:MAP3K7
3304:MAP3K9
3255:MAP3K8
3250:MAP3K7
3245:MAP3K6
3240:MAP3K5
3235:MAP3K4
3230:MAP3K3
3225:MAP3K2
3220:MAP3K1
3194:MAPK14
3189:MAPK13
3184:MAPK11
3172:MAPK10
3150:MAPK15
3145:MAPK12
3037:CDC2L1
3012:CDC2L5
2687:SNF1LK
2512:CAMK2G
2507:CAMK2D
2502:CAMK2B
2497:CAMK2A
2487:CAMK1G
2482:CAMK1D
2477:CAMK1B
2472:CAMK1A
2326:PRKCB1
2263:PRKACA
2258:PRKACB
2253:PRKACG
2229:IKBKAP
2055:BCKDHB
2050:BCKDHA
2024:PRKAG3
2019:PRKAG2
2014:PRKAG1
2004:PRKAB2
1999:PRKAB1
1989:PRKAA2
1984:PRKAA1
1829:STK38L
1688:
1678:
1643:
1608:
1563:
1528:
1488:
1453:
1418:
1377:
1367:
1311:
1303:
1293:
1254:
1044:search
1042:PubMed
909:Q8K4K4
890:Q96RU8
819:211770
786:Entrez
550:BioGPS
129:609461
3918:is a
3772:Types
3528:MAP2K
3462:ACVR1
3455:BMPR2
3440:BMPR1
3365:GSK-3
3206:MAP3K
3167:MAPK9
3162:MAPK8
3140:MAPK7
3135:MAPK6
3130:MAPK4
3125:MAPK3
3120:MAPK1
3032:PFTK1
3027:PCTK3
3022:PCTK2
3017:PCTK1
3007:CDK12
3002:CDK10
2977:CDKL5
2957:CDKL2
2834:STK19
2829:EEF2K
2810:PHKG2
2805:PHKG1
2795:PHKA2
2790:PHKA1
2771:MYLK4
2766:MYLK3
2761:MYLK2
2737:DCLK1
2732:Titin
2722:TRIB3
2717:TRIB2
2712:TRIB1
2702:TSSK2
2682:STK40
2667:PSKH1
2662:PRKD3
2657:PRKD2
2637:PHKG2
2632:PHKG1
2622:OBSCN
2617:NUAK2
2612:NUAK1
2607:MKNK2
2602:MKNK1
2592:MARK4
2587:MARK3
2582:MARK2
2577:MARK1
2557:STK11
2552:DAPK3
2547:DAPK2
2542:DAPK1
2537:CHEK2
2532:CHEK1
2517:CAMK4
2492:CAMK2
2467:CAMK1
2462:BRSK2
2356:PRKCQ
2351:PRKCI
2346:PRKCG
2341:PRKCH
2336:PRKCE
2331:PRKCD
2292:PRKG1
2224:IKBKG
2219:IKBKE
2168:STK10
2163:FASTK
2089:IDH3G
2084:IDH3B
2079:IDH3A
2045:BCKDK
1839:ROCK1
1824:STK38
1819:MAST2
1814:MAST1
1809:LATS2
1804:LATS1
1718:TRIB1
1706:TRIB1
1309:S2CID
1113:TRIB3
1109:TRIB2
1094:TRIB1
1088:is a
800:10221
779:Mouse
774:Human
745:Amigo
402:Mouse
395:Human
342:Start
277:Mouse
241:Start
174:Human
153:TRIB1
145:75216
112:TRIB1
22:TRIB1
3920:stub
3912:gene
3864:list
3857:EC7
3851:list
3844:EC6
3838:list
3831:EC5
3825:list
3818:EC4
3812:list
3805:EC3
3799:list
3792:EC2
3786:list
3779:EC1
3355:TPK1
3331:CDC7
3289:MLKs
3282:KSR2
3277:KSR1
3272:BRAF
3267:ARAF
3262:RAFs
2997:CDK9
2992:CDK8
2987:CDK7
2982:CDK6
2972:CDK5
2967:CDK4
2962:CDK3
2952:CDK2
2947:CDK1
2928:PLK4
2923:PLK3
2918:PLK2
2913:PLK1
2868:PLK4
2863:PLK3
2858:PLK2
2853:PLK1
2800:PHKB
2756:MYLK
2727:TRIO
2697:SPEG
2692:SNRK
2652:PKD1
2647:PIM2
2642:PIM1
2627:PASK
2597:MELK
2527:CASK
2522:MLCK
2443:GRK6
2438:GRK5
2433:GRK4
2371:PKN3
2366:PKN2
2268:PRKY
2214:TBK1
2209:IKK2
2204:CHUK
2108:STK4
2074:IDH2
1959:PDK4
1954:PDK3
1949:PDK2
1944:PDK1
1923:WEE1
1918:Wee1
1886:mTOR
1874:AKT3
1869:AKT2
1864:AKT1
1854:SGK3
1849:SGK2
1686:PMID
1641:PMID
1606:PMID
1561:PMID
1526:PMID
1486:PMID
1451:PMID
1416:PMID
1375:PMID
1301:PMID
1252:PMID
1111:and
1097:gene
520:lens
385:Bgee
333:Band
294:Chr.
232:Band
191:Chr.
125:OMIM
82:5IGQ
78:5IGO
74:5CEK
70:5CEM
51:RCSB
48:PDBe
3360:TTK
3324:ZAK
1901:HRI
1896:PKR
1844:SGK
1834:CIT
1676:PMC
1666:doi
1662:282
1631:doi
1627:281
1596:hdl
1586:doi
1582:279
1551:doi
1547:278
1518:doi
1478:doi
1474:104
1443:doi
1406:doi
1365:PMC
1357:doi
1291:PMC
1283:doi
1242:doi
1238:248
1099:.
524:lip
355:End
254:End
157:OMA
133:MGI
41:PDB
3965::
2010:Îł
1995:β
1980:α
1768:EC
1762::
1684:.
1674:.
1660:.
1656:.
1639:.
1625:.
1621:.
1604:.
1594:.
1580:.
1576:.
1559:.
1545:.
1541:.
1524:.
1514:39
1512:.
1484:.
1472:.
1449:.
1439:43
1437:.
1414:.
1402:23
1400:.
1396:.
1373:.
1363:.
1353:27
1351:.
1347:.
1335:^
1307:.
1299:.
1289:.
1279:63
1277:.
1273:.
1250:.
1236:.
1232:.
1213:.
1195:.
1166:^
1145:^
747:/
361:bp
348:bp
260:bp
247:bp
155:;
151::
147:;
143::
139:;
135::
131:;
127::
80:,
76:,
72:,
3951:e
3944:t
3937:v
3926:.
3880::
3866:)
3862:(
3853:)
3849:(
3840:)
3836:(
3827:)
3823:(
3814:)
3810:(
3801:)
3797:(
3788:)
3784:(
3608:e
3601:t
3594:v
3417:-
3400:-
3383:-
2186:-
1766:(
1752:e
1745:t
1738:v
1725:.
1713:.
1692:.
1668::
1647:.
1633::
1612:.
1598::
1588::
1567:.
1553::
1532:.
1520::
1492:.
1480::
1457:.
1445::
1422:.
1408::
1381:.
1359::
1329:.
1315:.
1285::
1258:.
1244::
1217:.
1199:.
279:)
176:)
159::
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